Hypertension
Treatment
Lifestyle modifications
The first line of treatment for hypertension is the same as the recommended preventative lifestyle changes such as the dietary changes, physical exercise, and weight loss, which have all been shown to significantly reduce blood pressure in people with hypertension.[55] If hypertension is high enough to justify immediate use of medications, lifestyle changes are still recommended in conjection with medication.
Biofeedback
Biofeedback devices can be used alone or in conjunction with lifestyle changes and/or medications to reduce hypertension. One example of Biofeedback is Resperate, a portable, battery-operated personal therapeutic medical device, sold over the counter in the United States. However, claims of efficacy for this particular device are not supported by scientific studies. Testimonials are used to promote such products, while no real evidence exists that the use of
Medications
Main article: Antihypertensive drugs
There are many classes of medications for treating hypertension, together called antihypertensives, which — by varying means — act by lowering blood pressure. Reduction of the blood pressure by 5–6 mmHg can decrease the risk of stroke by 40%, decrease the risk of heart disease by 15–20%, and reduce the likelihood of dementia, heart failure, and death.
The aim of treatment should be reduce blood pressure to <140/90 mmHg for most individuals, and lower individuals with diabetes or kidney disease (some medical professionals recommend keeping levels below 120/80 mmHg).[56] Each drug reduces systolic blood pressure by about 5–10 mmHg, so often multiple drugs are combined to achieve the goal blood pressure.
Commonly used prescription drugs include:[5]
• ACE inhibitors such as captopril, enalapril, fosinopril (Monopril), lisinopril (Zestril), quinapril, ramipril (Altace)
• Angiotensin II receptor antagonists may be used where ACE inhibitors are not tolerated: e.g., telmisartan (Micardis, Pritor), irbesartan (Avapro), losartan (Cozaar), valsartan (Diovan), candesartan (Amias), olmesartan (Benicar, Olmetec)
• Calcium channel blockers such as nifedipine (Adalat)[57] amlodipine (Norvasc), diltiazem, verapamil
• Diuretics: e.g., bendroflumethiazide, chlorthalidone, hydrochlorothiazide (also called HCTZ).
Other less commonly used prescription drugs include:
• Diuretics such a furosemide or low-dosages of spironolactone
• Alpha blockers such as prazosin, or terazosin. Doxazosin has been shown to the increase risk of heart failure, and to be less effective than a diuretics.[58]
• Beta blockers such as atenolol, labetalol, metoprolol (Lopressor, Toprol-XL), propranolol. Whilst once were first line agents, now they are less commonly used because they increase the risk of diabetes.[59]
• Direct renin inhibitors such as aliskiren (Tekturna).[60]
Thursday, June 17, 2010
Anti-diabetic drug
Anti-diabetic drug
Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.
Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected or inhaled.
Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents which increase the amount of insulin secreted by the pancreas, (2) agents which increase the sensitivity of target organs to insulin, and (3) agents which decrease the rate at which glucose is absorbed from the gastrointestinal tract.
Several groups of drugs, mostly given by mouth, are effective in Type II, often in combination. The therapeutic combination in Type II may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects. The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional doses, when blood glucose levels measured by the patient, usually with a simple meter, as needed by the measured amount of sugar in the blood.
Contents
• 1 Insulin
• 2 Secretagogues
o 2.1 Sulfonylureas
o 2.2 Meglitinides
• 3 Sensitizers
o 3.1 Biguanides
o 3.2 Thiazolidinediones
• 4 Alpha-glucosidase inhibitors
• 5 Peptide analogs
o 5.1 Incretin mimetics
5.1.1 Glucagon-like peptide (GLP) analogs and agonists
5.1.2 Gastric inhibitory peptide (GIP) analogs
o 5.2 DPP-4 inhibitors
o 5.3 Amylin analogues
• 6 Experimental agents
• 7 Alternative medicine
• 8 Notes
• 9 References
Insulin
Insulin is usually given subcutaneously, either by injections or by an insulin pump. Research is underway of other routes of administration. In acute care settings, insulin may also be given intravenously. There are several types of insulin, characterized by the rate which they are metabolized by the body.
Secretagogues
Sulfonylureas
Sulfonylureas were the first widely used oral hypoglycemic medications. They are insulin secretagogues, triggering insulin release by direct action on the KATP channel of the pancreatic beta cells. Eight types of these pills have been marketed in North America, but not all remain available. The "second-generation" drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side effects. All may cause weight gain.
Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia.
Typical reductions in A1C values for second generation sulfonylureas are 1.0-2.0%.
• First-generation agents
o tolbutamide (Orinase)
o acetohexamide (Dymelor)
o tolazamide (Tolinase)
o chlorpropamide (Diabinese)
• Second-generation agents
o glipizide (Glucotrol)
o glyburide (Diabeta, Micronase, Glynase)
o glimepiride (Amaryl)
o gliclazide (Diamicron)
Meglitinides
Meglitinides help the pancreas produce insulin and are often called "short-acting secretagogues." They act on the same potassium channels as sulfonylureas, but at a different binding site.[1] By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion.[2]
They are taken with or shortly before meals to boost the insulin response to each meal. If a meal is skipped, the medication is also skipped.
Typical reductions in A1C values are 0.5-1.0%.
• repaglinide (Prandin)
• nateglinide (Starlix)
Adverse reactions include weight gain and hypoglycemia.
Sensitizers
Insulin sensitizers address the core problem in Type II diabetes—insulin resistance. Among oral hypoglycemic agents, insulin sensitizers are the largest category.[3]
Biguanides
Main article: Biguanide
Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin, a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers. Amongst common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain.
Typical reductions in A1C values for metformin is 1.5-2.0%.
• metformin (Glucophage). Metformin may be the best choice for patients who also have heart failure.[4] Should be temporarily discontinued before any radiographic procedure involving intravenous iodinated contrast as patients are at an increased risk of lactic acidosis.
• phenformin (DBI): used from 1960s through 1980s, withdrawn due to lactic acidosis risk.[5]
• buformin: also withdrawn due to lactic acidosis risk.[6]
Metformin is usually the first-line medication used for treatment of type-2 diabetes. It is generally prescribed at initial diagnosis in conjunction with exercise and weight loss as opposed to in the past, where Metformin was prescribed after diet and exercise had failed. Initial dosing is 500 mg once daily, then if need be increased to 500 mg twice daily up to 1000 mg twice daily. It is also available in combination with other oral diabetic medications.
There is an extended release formulation available, but it is typically reserved for patients experiencing GI side effects.
Thiazolidinediones
Main article: Thiazolidinedione
Thiazolidinediones (TZDs), also known as "glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on Peroxysome Proliferator Responsive Elements (PPRE [1]). The PPREs influence insulin sensitive genes, which enhance production of mRNAs of insulin dependent enzymes. The final result is better use of glucose by the cells.
Typical reductions in A1C values are 1.5-2.0%.
• rosiglitazone (Avandia)
• pioglitazone (Actos)
• troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk.[7]
As a result of multiple retrospective studies, there is a concern about rosiglitazone's safety, although it is established that the group, as a whole, has beneficial effects on diabetes. The greatest concern is an increase in the number of severe cardiac events in patients taking it. The ADOPT study showed that initial therapy with drugs of this type may prevent the progression of disease,[8] as did the DREAM trial.[9]
Concerns about the safety of rosiglitazone arose when a retrospective meta-analysis was published in the New England Journal of Medicine.[10] There have been a significant number of publications since then, and a Food and Drug Administration panel[11] voted, with some controversy, 20:3 that available studies "supported a signal of harm," but voted 22:1 to keep the drug on the market. The meta-analysis was not supported by an interim analysis of the trial designed to evaluate the issue, and several other reports have failed to conclude the controversy. This weak evidence for adverse effects has reduced the use of rosiglitazone, despite its important and sustained effects on glycemic control.[12] Safety studies are continuing.
In contrast, at least one large prospective study, PROactive 05, has shown that pioglitazone may decrease the overall incidence of cardiac events in people with type II diabetes who have already had a heart attack.[13]
Alpha-glucosidase inhibitors
Alpha-glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.
Typical reductions in A1C values are 0.5-1.0%.
• miglitol (Glyset)
• acarbose (Precose/Glucobay)
These medications are rarely used in the United States because of the severity of their side effects (flatulence and bloating). They are more commonly prescribed in Europe. They do have the potential to cause weight loss by lowering the amount of sugar metabolized.
Research has shown the culinary mushroom Maitake (Grifola frondosa) has a hypoglycemic effect,[14][15][16][17][18][19] possibly due to the fact the mushroom naturally acts as an alpha-glucosidase inhibitor.[20]
Peptide analogs
Overview of insulin secretion
Incretin mimetics
Incretins are insulin secretagogues. The two main candidate molecules that fulfill criteria for being an incretin are Glucagon-like peptide-1 (GLP-1) and Gastric inhibitory peptide (aka glucose-dependent Insulinotropic peptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).
Glucagon-like peptide (GLP) analogs and agonists
GLP agonists bind to a membrane GLP receptor.[2] As a consequence of this, insulin release from the pancreatic beta cells is increased. Endogenous GLP has a half life of only a few minutes; thus an analogue of GLP would not be practical.
• Exenatide (also Exendin-4, marketed as Byetta) is the first GLP-1 agonist approved for the treatment of type 2 diabetes. Exenatide is not an analogue of GLP, but rather a GLP agonist.[21][22] Exenatide has only 53% homology with GLP, which increases its resistance to degradation by DPP-4 and extends its half-life.[23] Typical reductions in A1C values are 0.5-1.0%.
• Liraglutide, a once daily human analogue (97% homology), is being developed by Novo Nordisk under the brand name Victoza. The product was approved by the European Medicines Agency (EMEA) on July 3, 2009, and by the U.S. Food and Drug Administration (FDA) on January 25, 2010.[24][25][26][27][28][29]
• Taspoglutide is presently in Phase III Clinical Trials with Hoffman-La Roche.
These agents may also cause a decrease in gastric motility, responsible for the common side effect of nausea, and is probably the mechanism by which weight loss occurs.
Gastric inhibitory peptide (GIP) analogs
• None are FDA approved
DPP-4 inhibitors
Dipeptidyl peptidase-4 (DPP-4) inhibitors increase blood concentration of the incretin GLP-1 (glucagon-like peptide-1) by inhibiting its degradation by dipeptidyl peptidase-4 (DPP-4).
Typical reductions in A1C values are 0.5-1.0%.
Examples are:
• vildagliptin (Galvus) EU Approved 2008.
• sitagliptin (Januvia) FDA approved Oct 2006.
• saxagliptin (Onglyza) FDA Approved July 2009.
Amylin analogues
Amylin agonist analogues slow gastric emptying and suppress glucagon. They have all the incretins actions except stimulation of insulin secretion. As of 2007, pramlintide is the only clinically available amylin analogue. Like insulin, it is administered by subcutaneous injection. The most frequent and severe adverse effect of pramlintide is nausea, which occurs mostly at the beginning of treatment and gradually reduces. Typical reductions in A1C values are 0.5-1.0%.
Experimental agents
Many other potential drugs are currently in investigation by pharmaceutical companies. Some of these are simply newer members of one of the above classes, but some work by novel mechanisms. For example, at least one compound that enhances the sensitivity of glucokinase to rising glucose is in the stage of animal research. Others are undergoing phase I/II studies.
• PPARα/γ ligands (muraglitazar and tesaglitazar - development stopped due to adverse risk profile, aleglitazar - under clinical development)
• SGLT2 (sodium-dependent glucose transporter 2) inhibitors increase urinary glucose.
• FBPase (fructose 1,6-bisphosphatase) inhibitors decrease gluconeogenesis in the liver.
Alternative medicine
A recent review article presents the profiles of plants with hypoglycaemic properties, reported in the literature from 1990 to 2000 and states that "Medical plants play an important role in the management of diabetes mellitus especially in developing countries where resources are meager."[30]
The first registered use of anti-diabetic drugs was as herbal extracts used by Indians in the Amazon Basin for the treatment of type 2 diabetes, and today promoted as vegetable insulin although not formally an insulin analog.[31] The major recent development was done in Brazil around Myrcia sphaerocarpa and other Myrcia species.[32] The usual treatment is with concentrated (root) Myrcia extracts, commercialized as "Pedra hume de kaá". Phytochemical analysis of the Myrcia extracts reported kinds of flavanone glucosides (myrciacitrins) and acetophenone glucosides (myrciaphenones), and inhibitory activities on aldose reductase and alpha-glucosidase.[33]
Walnut leaf can significantly reduce fasting blood glucose levels in rats with alloxan-induced diabetes, and rats thus treates show some evidence of regeneration of the beta cells.[34] Garlic also significantly reduces fasting blood glucose levels in rats with alloxan-induced diabetes.[35]
At least two studies have shown that cinnamon can act significantly reducing some effects of diabetes. One study on people used fine ground cassia (Cinnamomum aromaticum) for oral consumption. Another study used an extract (MHCP) on laboratory rats. The study on people published in 2003 conducted in the Department of Human Nutrition, NWFP Agricultural University, Peshawar, Pakistan concluded "that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases."[36] The study on laboratory rats at Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University published in 2001 used purified hydroxychalcone (MHCP) from cinnamon. Part of the study's conclusion stated that "the MHCP is fully capable of mimicking insulin" and recommended further studies.[37][38] The Food and Drug Administration has not yet evaluated the use of cinnamon for the management of diabetes. It should be noted that the spice sold as cinnamon is often obtained from C. verum (true cinnamon), not C. aromaticum (cassia).
Research has shown the Maitake mushroom (Grifola frondosa) has a hypoglycemic effect, and may be beneficial for the management of diabetes.[14][15][16][17][18][19] The reason Maitake lowers blood sugar is due to the fact the mushroom naturally acts as an alpha glucosidase inhibitor.[2] Other mushrooms like Reishi,[39][40] Agaricus blazei,[41][42][43][44] Agrocybe cylindracea[45] and Cordyceps[46][47][48][49][50] have been noted to lower blood sugar levels to a certain extent, although the mechanism is currently unknown.
Cinnamon
Though not yet evaluated by the Food and Drug Administration, at least two studies have shown that cinnamon can act significantly reducing some effects of diabetes. One study on people used fine ground cinnamon (Cinnamomum cassia) for oral consumption. Another study used an extract (MHCP) on laboratory rats.
The study on people published in 2003 conducted in the Department of Human Nutrition, NWFP Agricultural University, Peshawar, Pakistan concluded:
The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.[51]
The study on laboratory rats at Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University published in 2001 used purified hydroxychalcone from cinnamon. The extract was named "MHCP". Part of the study's conclusion stated that "the MHCP is fully capable of mimicking insulin" and recommended further studies.[52][53]
Other studies have failed to reproduce these results, and, because large doses of cinnamon are not innocuous, some experts advise against treatment of diabetes with cinnamon.[54]
Chromium and vanadium
Chromium - Cholesterol and triglycerides are risk factors in heart disease and diabetes, and studies show that chromium lowers levels of total cholesterol, LDL cholesterol, and triglycerides.[55][56][57][58] Chromium supplements such as chromium picolinate have been shown to improve glucose tolerance in people with type 2 diabetes,[59][60][61] although other studies have not replicated this result.[62] A meta analysis of these trials concluded that chromium supplements had no beneficial effect on healthy people, but that there might be an improvement in glucose metabolism in diabetics, although the authors stated that the evidence for this effect remains weak.[63]
Vanadium - A form of vanadium, vanadyl sulfate, seems to improve glucose control in people with type 2 diabetes.[64][65][66][67][68]
A pilot study has also found evidence that Tai Chi and Qigong reduce the severity of type 2 diabetes.[69]
Benfotiamine, a pro-vitamin of vitamin B1 which has been in use in Europe as an over-the-counter medicine for alcoholic neuropathy for the past half century with no significant side-effects or toxicity, has recently been found to block the major metabolic pathways by which excess blood glucose in the body is transformed into the advanced glycation endproducts (AGEs) which cause diabetic complications.[70] Studies have shown that taking oral benfotiamine can prevent diabetic retinopathy,[71] diabetic neuropathy,[72] and diabetic nephropathy[73] independently of any affect on the blood sugar levels of the patient. In theory, taking benfotiamine might allow patients to be less scrupulous in trying to normalize blood sugar levels and thus free them from the danger of hypoglycemia and the stress of stringent blood sugar monitoring, while still protecting them against the negative effects of hyperglycemia. Research is ongoing to establish the full significance of benfotiamine in the treatment of diabetes.
Traditional plant treatments for diabetes
A study was made of the effects on glucose homeostasis in normal and streptozotocin (induced) diabetic mice of eleven plants that have been used as traditional treatments for diabetes. The mice were given diets containing dried leaves from the following plants: agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra). The study concluded that "The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice".[74]
Mushrooms
Research has shown the Maitake mushroom (Grifola frondosa) has a hypoglycemic effect, and may be beneficial for the management of diabetes.[14][15][16][17][18][19] The reason Maitake lowers blood sugar is due to the fact the mushroom naturally acts as an alpha glucosidase inhibitor.[75] Other mushrooms like Reishi,[39][40] Agaricus blazei,[41][42][43][76] Agrocybe cylindracea[77] and Cordyceps[46][47][48][49][50] have been noted to lower blood sugar levels to a certain extent, although the mechanism is currently unknown.
Aloe vera Oral administration of aloe vera might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia[citation needed]. Ten controlled clinical trials were found to reach that conclusion in four independent literature searches. However, caveats reported in each study led the researchers to conclude that aloe vera's clinical effectiveness was not yet sufficiently defined in 1999.[78]
Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.
Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected or inhaled.
Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents which increase the amount of insulin secreted by the pancreas, (2) agents which increase the sensitivity of target organs to insulin, and (3) agents which decrease the rate at which glucose is absorbed from the gastrointestinal tract.
Several groups of drugs, mostly given by mouth, are effective in Type II, often in combination. The therapeutic combination in Type II may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects. The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional doses, when blood glucose levels measured by the patient, usually with a simple meter, as needed by the measured amount of sugar in the blood.
Contents
• 1 Insulin
• 2 Secretagogues
o 2.1 Sulfonylureas
o 2.2 Meglitinides
• 3 Sensitizers
o 3.1 Biguanides
o 3.2 Thiazolidinediones
• 4 Alpha-glucosidase inhibitors
• 5 Peptide analogs
o 5.1 Incretin mimetics
5.1.1 Glucagon-like peptide (GLP) analogs and agonists
5.1.2 Gastric inhibitory peptide (GIP) analogs
o 5.2 DPP-4 inhibitors
o 5.3 Amylin analogues
• 6 Experimental agents
• 7 Alternative medicine
• 8 Notes
• 9 References
Insulin
Insulin is usually given subcutaneously, either by injections or by an insulin pump. Research is underway of other routes of administration. In acute care settings, insulin may also be given intravenously. There are several types of insulin, characterized by the rate which they are metabolized by the body.
Secretagogues
Sulfonylureas
Sulfonylureas were the first widely used oral hypoglycemic medications. They are insulin secretagogues, triggering insulin release by direct action on the KATP channel of the pancreatic beta cells. Eight types of these pills have been marketed in North America, but not all remain available. The "second-generation" drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side effects. All may cause weight gain.
Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. The primary side effect is hypoglycemia.
Typical reductions in A1C values for second generation sulfonylureas are 1.0-2.0%.
• First-generation agents
o tolbutamide (Orinase)
o acetohexamide (Dymelor)
o tolazamide (Tolinase)
o chlorpropamide (Diabinese)
• Second-generation agents
o glipizide (Glucotrol)
o glyburide (Diabeta, Micronase, Glynase)
o glimepiride (Amaryl)
o gliclazide (Diamicron)
Meglitinides
Meglitinides help the pancreas produce insulin and are often called "short-acting secretagogues." They act on the same potassium channels as sulfonylureas, but at a different binding site.[1] By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion.[2]
They are taken with or shortly before meals to boost the insulin response to each meal. If a meal is skipped, the medication is also skipped.
Typical reductions in A1C values are 0.5-1.0%.
• repaglinide (Prandin)
• nateglinide (Starlix)
Adverse reactions include weight gain and hypoglycemia.
Sensitizers
Insulin sensitizers address the core problem in Type II diabetes—insulin resistance. Among oral hypoglycemic agents, insulin sensitizers are the largest category.[3]
Biguanides
Main article: Biguanide
Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin, a biguanide, has become the most commonly used agent for type 2 diabetes in children and teenagers. Amongst common diabetic drugs, metformin is the only widely used oral drug that does not cause weight gain.
Typical reductions in A1C values for metformin is 1.5-2.0%.
• metformin (Glucophage). Metformin may be the best choice for patients who also have heart failure.[4] Should be temporarily discontinued before any radiographic procedure involving intravenous iodinated contrast as patients are at an increased risk of lactic acidosis.
• phenformin (DBI): used from 1960s through 1980s, withdrawn due to lactic acidosis risk.[5]
• buformin: also withdrawn due to lactic acidosis risk.[6]
Metformin is usually the first-line medication used for treatment of type-2 diabetes. It is generally prescribed at initial diagnosis in conjunction with exercise and weight loss as opposed to in the past, where Metformin was prescribed after diet and exercise had failed. Initial dosing is 500 mg once daily, then if need be increased to 500 mg twice daily up to 1000 mg twice daily. It is also available in combination with other oral diabetic medications.
There is an extended release formulation available, but it is typically reserved for patients experiencing GI side effects.
Thiazolidinediones
Main article: Thiazolidinedione
Thiazolidinediones (TZDs), also known as "glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on Peroxysome Proliferator Responsive Elements (PPRE [1]). The PPREs influence insulin sensitive genes, which enhance production of mRNAs of insulin dependent enzymes. The final result is better use of glucose by the cells.
Typical reductions in A1C values are 1.5-2.0%.
• rosiglitazone (Avandia)
• pioglitazone (Actos)
• troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk.[7]
As a result of multiple retrospective studies, there is a concern about rosiglitazone's safety, although it is established that the group, as a whole, has beneficial effects on diabetes. The greatest concern is an increase in the number of severe cardiac events in patients taking it. The ADOPT study showed that initial therapy with drugs of this type may prevent the progression of disease,[8] as did the DREAM trial.[9]
Concerns about the safety of rosiglitazone arose when a retrospective meta-analysis was published in the New England Journal of Medicine.[10] There have been a significant number of publications since then, and a Food and Drug Administration panel[11] voted, with some controversy, 20:3 that available studies "supported a signal of harm," but voted 22:1 to keep the drug on the market. The meta-analysis was not supported by an interim analysis of the trial designed to evaluate the issue, and several other reports have failed to conclude the controversy. This weak evidence for adverse effects has reduced the use of rosiglitazone, despite its important and sustained effects on glycemic control.[12] Safety studies are continuing.
In contrast, at least one large prospective study, PROactive 05, has shown that pioglitazone may decrease the overall incidence of cardiac events in people with type II diabetes who have already had a heart attack.[13]
Alpha-glucosidase inhibitors
Alpha-glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.
Typical reductions in A1C values are 0.5-1.0%.
• miglitol (Glyset)
• acarbose (Precose/Glucobay)
These medications are rarely used in the United States because of the severity of their side effects (flatulence and bloating). They are more commonly prescribed in Europe. They do have the potential to cause weight loss by lowering the amount of sugar metabolized.
Research has shown the culinary mushroom Maitake (Grifola frondosa) has a hypoglycemic effect,[14][15][16][17][18][19] possibly due to the fact the mushroom naturally acts as an alpha-glucosidase inhibitor.[20]
Peptide analogs
Overview of insulin secretion
Incretin mimetics
Incretins are insulin secretagogues. The two main candidate molecules that fulfill criteria for being an incretin are Glucagon-like peptide-1 (GLP-1) and Gastric inhibitory peptide (aka glucose-dependent Insulinotropic peptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).
Glucagon-like peptide (GLP) analogs and agonists
GLP agonists bind to a membrane GLP receptor.[2] As a consequence of this, insulin release from the pancreatic beta cells is increased. Endogenous GLP has a half life of only a few minutes; thus an analogue of GLP would not be practical.
• Exenatide (also Exendin-4, marketed as Byetta) is the first GLP-1 agonist approved for the treatment of type 2 diabetes. Exenatide is not an analogue of GLP, but rather a GLP agonist.[21][22] Exenatide has only 53% homology with GLP, which increases its resistance to degradation by DPP-4 and extends its half-life.[23] Typical reductions in A1C values are 0.5-1.0%.
• Liraglutide, a once daily human analogue (97% homology), is being developed by Novo Nordisk under the brand name Victoza. The product was approved by the European Medicines Agency (EMEA) on July 3, 2009, and by the U.S. Food and Drug Administration (FDA) on January 25, 2010.[24][25][26][27][28][29]
• Taspoglutide is presently in Phase III Clinical Trials with Hoffman-La Roche.
These agents may also cause a decrease in gastric motility, responsible for the common side effect of nausea, and is probably the mechanism by which weight loss occurs.
Gastric inhibitory peptide (GIP) analogs
• None are FDA approved
DPP-4 inhibitors
Dipeptidyl peptidase-4 (DPP-4) inhibitors increase blood concentration of the incretin GLP-1 (glucagon-like peptide-1) by inhibiting its degradation by dipeptidyl peptidase-4 (DPP-4).
Typical reductions in A1C values are 0.5-1.0%.
Examples are:
• vildagliptin (Galvus) EU Approved 2008.
• sitagliptin (Januvia) FDA approved Oct 2006.
• saxagliptin (Onglyza) FDA Approved July 2009.
Amylin analogues
Amylin agonist analogues slow gastric emptying and suppress glucagon. They have all the incretins actions except stimulation of insulin secretion. As of 2007, pramlintide is the only clinically available amylin analogue. Like insulin, it is administered by subcutaneous injection. The most frequent and severe adverse effect of pramlintide is nausea, which occurs mostly at the beginning of treatment and gradually reduces. Typical reductions in A1C values are 0.5-1.0%.
Experimental agents
Many other potential drugs are currently in investigation by pharmaceutical companies. Some of these are simply newer members of one of the above classes, but some work by novel mechanisms. For example, at least one compound that enhances the sensitivity of glucokinase to rising glucose is in the stage of animal research. Others are undergoing phase I/II studies.
• PPARα/γ ligands (muraglitazar and tesaglitazar - development stopped due to adverse risk profile, aleglitazar - under clinical development)
• SGLT2 (sodium-dependent glucose transporter 2) inhibitors increase urinary glucose.
• FBPase (fructose 1,6-bisphosphatase) inhibitors decrease gluconeogenesis in the liver.
Alternative medicine
A recent review article presents the profiles of plants with hypoglycaemic properties, reported in the literature from 1990 to 2000 and states that "Medical plants play an important role in the management of diabetes mellitus especially in developing countries where resources are meager."[30]
The first registered use of anti-diabetic drugs was as herbal extracts used by Indians in the Amazon Basin for the treatment of type 2 diabetes, and today promoted as vegetable insulin although not formally an insulin analog.[31] The major recent development was done in Brazil around Myrcia sphaerocarpa and other Myrcia species.[32] The usual treatment is with concentrated (root) Myrcia extracts, commercialized as "Pedra hume de kaá". Phytochemical analysis of the Myrcia extracts reported kinds of flavanone glucosides (myrciacitrins) and acetophenone glucosides (myrciaphenones), and inhibitory activities on aldose reductase and alpha-glucosidase.[33]
Walnut leaf can significantly reduce fasting blood glucose levels in rats with alloxan-induced diabetes, and rats thus treates show some evidence of regeneration of the beta cells.[34] Garlic also significantly reduces fasting blood glucose levels in rats with alloxan-induced diabetes.[35]
At least two studies have shown that cinnamon can act significantly reducing some effects of diabetes. One study on people used fine ground cassia (Cinnamomum aromaticum) for oral consumption. Another study used an extract (MHCP) on laboratory rats. The study on people published in 2003 conducted in the Department of Human Nutrition, NWFP Agricultural University, Peshawar, Pakistan concluded "that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases."[36] The study on laboratory rats at Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University published in 2001 used purified hydroxychalcone (MHCP) from cinnamon. Part of the study's conclusion stated that "the MHCP is fully capable of mimicking insulin" and recommended further studies.[37][38] The Food and Drug Administration has not yet evaluated the use of cinnamon for the management of diabetes. It should be noted that the spice sold as cinnamon is often obtained from C. verum (true cinnamon), not C. aromaticum (cassia).
Research has shown the Maitake mushroom (Grifola frondosa) has a hypoglycemic effect, and may be beneficial for the management of diabetes.[14][15][16][17][18][19] The reason Maitake lowers blood sugar is due to the fact the mushroom naturally acts as an alpha glucosidase inhibitor.[2] Other mushrooms like Reishi,[39][40] Agaricus blazei,[41][42][43][44] Agrocybe cylindracea[45] and Cordyceps[46][47][48][49][50] have been noted to lower blood sugar levels to a certain extent, although the mechanism is currently unknown.
Cinnamon
Though not yet evaluated by the Food and Drug Administration, at least two studies have shown that cinnamon can act significantly reducing some effects of diabetes. One study on people used fine ground cinnamon (Cinnamomum cassia) for oral consumption. Another study used an extract (MHCP) on laboratory rats.
The study on people published in 2003 conducted in the Department of Human Nutrition, NWFP Agricultural University, Peshawar, Pakistan concluded:
The results of this study demonstrate that intake of 1, 3, or 6 g of cinnamon per day reduces serum glucose, triglyceride, LDL cholesterol, and total cholesterol in people with type 2 diabetes and suggest that the inclusion of cinnamon in the diet of people with type 2 diabetes will reduce risk factors associated with diabetes and cardiovascular diseases.[51]
The study on laboratory rats at Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University published in 2001 used purified hydroxychalcone from cinnamon. The extract was named "MHCP". Part of the study's conclusion stated that "the MHCP is fully capable of mimicking insulin" and recommended further studies.[52][53]
Other studies have failed to reproduce these results, and, because large doses of cinnamon are not innocuous, some experts advise against treatment of diabetes with cinnamon.[54]
Chromium and vanadium
Chromium - Cholesterol and triglycerides are risk factors in heart disease and diabetes, and studies show that chromium lowers levels of total cholesterol, LDL cholesterol, and triglycerides.[55][56][57][58] Chromium supplements such as chromium picolinate have been shown to improve glucose tolerance in people with type 2 diabetes,[59][60][61] although other studies have not replicated this result.[62] A meta analysis of these trials concluded that chromium supplements had no beneficial effect on healthy people, but that there might be an improvement in glucose metabolism in diabetics, although the authors stated that the evidence for this effect remains weak.[63]
Vanadium - A form of vanadium, vanadyl sulfate, seems to improve glucose control in people with type 2 diabetes.[64][65][66][67][68]
A pilot study has also found evidence that Tai Chi and Qigong reduce the severity of type 2 diabetes.[69]
Benfotiamine, a pro-vitamin of vitamin B1 which has been in use in Europe as an over-the-counter medicine for alcoholic neuropathy for the past half century with no significant side-effects or toxicity, has recently been found to block the major metabolic pathways by which excess blood glucose in the body is transformed into the advanced glycation endproducts (AGEs) which cause diabetic complications.[70] Studies have shown that taking oral benfotiamine can prevent diabetic retinopathy,[71] diabetic neuropathy,[72] and diabetic nephropathy[73] independently of any affect on the blood sugar levels of the patient. In theory, taking benfotiamine might allow patients to be less scrupulous in trying to normalize blood sugar levels and thus free them from the danger of hypoglycemia and the stress of stringent blood sugar monitoring, while still protecting them against the negative effects of hyperglycemia. Research is ongoing to establish the full significance of benfotiamine in the treatment of diabetes.
Traditional plant treatments for diabetes
A study was made of the effects on glucose homeostasis in normal and streptozotocin (induced) diabetic mice of eleven plants that have been used as traditional treatments for diabetes. The mice were given diets containing dried leaves from the following plants: agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra). The study concluded that "The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice".[74]
Mushrooms
Research has shown the Maitake mushroom (Grifola frondosa) has a hypoglycemic effect, and may be beneficial for the management of diabetes.[14][15][16][17][18][19] The reason Maitake lowers blood sugar is due to the fact the mushroom naturally acts as an alpha glucosidase inhibitor.[75] Other mushrooms like Reishi,[39][40] Agaricus blazei,[41][42][43][76] Agrocybe cylindracea[77] and Cordyceps[46][47][48][49][50] have been noted to lower blood sugar levels to a certain extent, although the mechanism is currently unknown.
Aloe vera Oral administration of aloe vera might be a useful adjunct for lowering blood glucose in diabetic patients as well as for reducing blood lipid levels in patients with hyperlipidaemia[citation needed]. Ten controlled clinical trials were found to reach that conclusion in four independent literature searches. However, caveats reported in each study led the researchers to conclude that aloe vera's clinical effectiveness was not yet sufficiently defined in 1999.[78]
Huntington's disease -clinical research
Huntington's disease clinical research
There are different therapies under investigation for Huntington's disease. Huntington's disease is a is a genetic neurological disorder characterized after onset by uncoordinated, jerky body movements and a decline in some mental abilities for which there is no cure or effective treatments. Animal models help in the ongoing investigations using intrabody therapy, gene silencing, or stem cell implants, but all are at their first steps. Several clinical trials of various compounds are also in development. Many of these trials use the unified Huntington's disease rating scale (UHDRS) developed by the Huntington's Study Group.[1] This provides an overall rating system based on motor, behavioral, cognitive, and functional assessments, backed up by a reference database of previous results provided by HSG for reference.[2] Another avenue of research is understanding the physical mechanics of protein folding, HD is one of several targets of the folding@home project,[3] one of the largest distributed computing systems on the World Wide Web.
Contents
• Animal models
• Intrabody therapy
• Gene silencing
• Stem cell treatments
• Pharmacological
Animal models
A laboratory mouse
Appropriate animal models are critical for understanding the fundamental mechanisms causing the disease and for supporting the early stages of drug development. Neurochemically-induced mice or monkeys were first available,[5][6] but they did not mimic the progressive features of the disease. After the HD gene was discovered, transgenic animals exhibiting HD were generated by inserting a CAG repeat expansion into the genome, of mice (strain R6/2),[7][8]), Drosophila fruit flies,[9] and more recently monkeys.[10] Expression without insertion of a DNA repeat in nematode worms also produced a valuable model.[11]
Intrabody therapy
Genetically-engineered intracellular antibody fragments called intrabodies have shown therapeutic results, by inhibiting mHtt aggregation, in Drosophila models. This was achieved using an intrabody called C4 sFv, a single chain variable fragment which binds to the end of mHtt within a cell. This therapy prevented larval and pupal mortality (without therapy 77% died) and delayed neurodegeneration in the adult, significantly increasing their lifespan.[14] Intrabodies have shown promise as a useful tool for drug discovery, and may potentially be used as a therapy for HD and other neurodegenerative disorders caused by protein mis-folding or abnormal protein interactions.
Gene silencing
As HD has been conclusively linked to a single gene, gene silencing is potentially possible. Researchers have investigated using gene knockdown of mHTT as a potential treatment. Using a mouse model, siRNA therapy achieved a 60% reduction in expression of mHTT and progression of the disease was stalled.[17] However, this study used the human form of the mHTT protein in mice, and was therefore only able to directly target the mHTT, leaving endogenous, wild-type mouse Htt gene expression unaffected. From a practical standpoint, it would be difficult in humans to use siRNA to target the mutant form while leaving the normal copy unaffected. The precise function of Hyy is unknown, but in mice, complete deletion of the Htt gene is lethal. Thus, using RNA interference to treat HD could have unexpected effects unless knock-down of the normal Htt protein can be avoided. Other issues include problems delivering the siRNA to the appropriate target tissue, off-target effects of siRNA, and toxicity from shRNA over-expression. Another study showed that mouse models already in late stages of the disease recovered motor function after expression of mHTT was stopped.
Stem cell treatments
Main article: Stem cell treatments
Stem cell implants are a stem cell treatment where damaged neurons are replaced by transplantation of stem cells (or possibly neural stem cells—a type of somatic [adult] stem cell) into affected regions of the brain. Hypothetically, embryonic stem cells can be differentiated into neuronal precursors in vitro, and transplanted into damaged areas of the brain to generate replacement neurons; if enough damaged neurons can be replaced and develop the correct synaptic connectivity, symptoms could be alleviated. This treatment would not prevent further neuronal damage, so it would have to be an ongoing treatment. Experiments have yielded some positive results in animal models, but stem cell treatment for HD remains highly speculative and has not been tested in clinical trials.
Pharmacological
As of August 2008, several trials of various compounds are in development or ongoing,[22] a few at the point of testing on larger numbers of people, known as phase III of clinical trials. Substances that have shown promise in initial experiments include dopamine receptor blockers, select dopamine antagonists, such as creatine and CoQ10, the antibiotic Minocycline, antioxidant-containing foods and nutrients, and antidepressants, including selective serotonin reuptake inhibitors such as sertraline, fluoxetine, and paroxetine. A recent study suggested strong association between specific single nucleotide polymorphisms alleles and CAG expansion also provides an opportunity of personalized therapeutics in HD where the clinical development of only a small number of allele-specific targets may be sufficient to treat up to 88% of the HD patient population.
There are different therapies under investigation for Huntington's disease. Huntington's disease is a is a genetic neurological disorder characterized after onset by uncoordinated, jerky body movements and a decline in some mental abilities for which there is no cure or effective treatments. Animal models help in the ongoing investigations using intrabody therapy, gene silencing, or stem cell implants, but all are at their first steps. Several clinical trials of various compounds are also in development. Many of these trials use the unified Huntington's disease rating scale (UHDRS) developed by the Huntington's Study Group.[1] This provides an overall rating system based on motor, behavioral, cognitive, and functional assessments, backed up by a reference database of previous results provided by HSG for reference.[2] Another avenue of research is understanding the physical mechanics of protein folding, HD is one of several targets of the folding@home project,[3] one of the largest distributed computing systems on the World Wide Web.
Contents
• Animal models
• Intrabody therapy
• Gene silencing
• Stem cell treatments
• Pharmacological
Animal models
A laboratory mouse
Appropriate animal models are critical for understanding the fundamental mechanisms causing the disease and for supporting the early stages of drug development. Neurochemically-induced mice or monkeys were first available,[5][6] but they did not mimic the progressive features of the disease. After the HD gene was discovered, transgenic animals exhibiting HD were generated by inserting a CAG repeat expansion into the genome, of mice (strain R6/2),[7][8]), Drosophila fruit flies,[9] and more recently monkeys.[10] Expression without insertion of a DNA repeat in nematode worms also produced a valuable model.[11]
Intrabody therapy
Genetically-engineered intracellular antibody fragments called intrabodies have shown therapeutic results, by inhibiting mHtt aggregation, in Drosophila models. This was achieved using an intrabody called C4 sFv, a single chain variable fragment which binds to the end of mHtt within a cell. This therapy prevented larval and pupal mortality (without therapy 77% died) and delayed neurodegeneration in the adult, significantly increasing their lifespan.[14] Intrabodies have shown promise as a useful tool for drug discovery, and may potentially be used as a therapy for HD and other neurodegenerative disorders caused by protein mis-folding or abnormal protein interactions.
Gene silencing
As HD has been conclusively linked to a single gene, gene silencing is potentially possible. Researchers have investigated using gene knockdown of mHTT as a potential treatment. Using a mouse model, siRNA therapy achieved a 60% reduction in expression of mHTT and progression of the disease was stalled.[17] However, this study used the human form of the mHTT protein in mice, and was therefore only able to directly target the mHTT, leaving endogenous, wild-type mouse Htt gene expression unaffected. From a practical standpoint, it would be difficult in humans to use siRNA to target the mutant form while leaving the normal copy unaffected. The precise function of Hyy is unknown, but in mice, complete deletion of the Htt gene is lethal. Thus, using RNA interference to treat HD could have unexpected effects unless knock-down of the normal Htt protein can be avoided. Other issues include problems delivering the siRNA to the appropriate target tissue, off-target effects of siRNA, and toxicity from shRNA over-expression. Another study showed that mouse models already in late stages of the disease recovered motor function after expression of mHTT was stopped.
Stem cell treatments
Main article: Stem cell treatments
Stem cell implants are a stem cell treatment where damaged neurons are replaced by transplantation of stem cells (or possibly neural stem cells—a type of somatic [adult] stem cell) into affected regions of the brain. Hypothetically, embryonic stem cells can be differentiated into neuronal precursors in vitro, and transplanted into damaged areas of the brain to generate replacement neurons; if enough damaged neurons can be replaced and develop the correct synaptic connectivity, symptoms could be alleviated. This treatment would not prevent further neuronal damage, so it would have to be an ongoing treatment. Experiments have yielded some positive results in animal models, but stem cell treatment for HD remains highly speculative and has not been tested in clinical trials.
Pharmacological
As of August 2008, several trials of various compounds are in development or ongoing,[22] a few at the point of testing on larger numbers of people, known as phase III of clinical trials. Substances that have shown promise in initial experiments include dopamine receptor blockers, select dopamine antagonists, such as creatine and CoQ10, the antibiotic Minocycline, antioxidant-containing foods and nutrients, and antidepressants, including selective serotonin reuptake inhibitors such as sertraline, fluoxetine, and paroxetine. A recent study suggested strong association between specific single nucleotide polymorphisms alleles and CAG expansion also provides an opportunity of personalized therapeutics in HD where the clinical development of only a small number of allele-specific targets may be sufficient to treat up to 88% of the HD patient population.
DIALYSIS
DIALYSIS
What is dialysis?
The kidneys are responsible for filtering waste products from the blood. Dialysis is a procedure that is a substitute for many of the normal duties of the kidneys. The kidneys are two organs located on either side of the back of the abdominal cavity. Dialysis can allow individuals to live productive and useful lives, even though their kidneys no longer work adequately. In the United States, there are over 200,000 people who use dialysis techniques on an ongoing basis.
Dialysis helps the body by performing the functions of failed kidneys. The kidney has many roles. An essential job of the kidney is to regulate the body's fluid balance. It does this by adjusting the amount of urine that is excreted on a daily basis. On hot days, the body sweats more. Thus, less water needs to be excreted through the kidneys. On cold days, the body sweats less. Thus, urine output needs to be greater in order to maintain the proper balance within the body. It is the kidney's job to regulate fluid balance by adjusting urine output.
Another major duty of the kidney is to remove the waste products that the body produces throughout the day. As the body functions, the cells use energy. The operation of the cells produces waste products that must be removed from the body. When these waste products are not removed adequately, they build up in the body. An elevation of waste products, as measured in the blood, is called "azotemia." When waste products accumulate they, cause a sick feeling throughout the body called "uremia."
When do patients require dialysis?
Patients usually require dialysis when the waste products in their body become so high that they start to become sick from them. The level of the waste products usually builds up slowly. Doctors measure several blood chemical levels to help decide when dialysis is necessary. The two major blood chemical levels that are measured are the "creatinine level" and the "blood urea nitrogen" (BUN) level. As these two levels rise, they are indicators of the decreasing ability of the kidneys to cleanse the body of waste products.
Doctors use a urine test, the "creatinine clearance," to measure the level of kidney function. The patient saves urine in a special container for one full day. The waste products in the urine and in the blood are estimated by measuring the creatinine. By comparing the blood and urine level of this substance, the doctor has an accurate idea of how well the kidneys are working. This result is called the creatinine clearance. Usually, when the creatinine clearance falls to 10-12 cc/minute, the patient needs dialysis.
The doctor uses other indicators of the patient's status to decide about the need for dialysis. If the patient is experiencing a major inability to rid the body of excess water, or is complaining of problems with the heart, lungs, or stomach, or difficulties with taste or sensation in their legs, dialysis may be indicated even though the creatinine clearance has not fallen to the 10-12 cc/minute level.
What types of dialysis are there?
There are two main types of dialysis: "hemodialysis" and "peritoneal dialysis." Hemodialysis uses a special type of filter to remove excess waste products and water from the body. Peritoneal dialysis uses a fluid that is placed into the patient's stomach cavity through a special plastic tube to remove excess waste products and fluid from the body.
During Hemodialysis, blood passes from the patient's body through a filter in the dialysis machine, called a "dialysis membrane." For this procedure, the patient has a specialized plastic tube placed between an artery and a vein in the arm or leg (called a "gortex graft"). Sometimes, a direct connection is made between an artery and a vein in the arm. This procedure is called a "Cimino fistula." Needles are then placed in the graft or fistula, and blood passes to the dialysis machine, through the filter, and back to the patient. In the dialysis machine, a solution on the other side of the filter receives the waste products from the patient.
Peritoneal dialysis uses the patients own body tissues inside of the belly (abdominal cavity) to act as the filter. The intestines lie in the abdominal cavity, the space between the abdominal wall and the spine. A plastic tube called a "dialysis catheter" is placed through the abdominal wall into the abdominal cavity. A special fluid is then flushed into the abdominal cavity and washes around the intestines. The intestinal walls act as a filter between this fluid and the blood stream. By using different types of solutions, waste products and excess water can be removed from the body through this process.
What does the patient do during dialysis?
Hemodialysis
Treatment for hemodialysis takes place in a hemodialysis unit. This is a special building that is equipped with machines that perform the dialysis treatment. Special equipment adds the proper materials to purified water for the dialysis machines. The dialysis unit is also the place where patients can receive dietary counseling and help with social needs.
Patients generally go to the dialysis unit three times a week for treatment. For example, the schedule is either on Monday, Wednesday, and Friday or Tuesday, Thursday, and Saturday. Before treatment, patients weigh themselves so that excess fluid accumulated since the last dialysis session can be measured. Patients then go to assigned chairs that are like lounge chairs. The area of the graft or fistula (the connection between the artery and vein), is cleaned thoroughly. Two needles are then inserted into the graft or fistula. One takes the blood to the machine where it is cleaned. The other needle allows blood that is returning to the patient to go back into the patient's body.
Treatments last from 2 ½ to 4 ½ hours. During this time, the dialysis staff checks the patient's blood pressure frequently and adjusts the dialysis machine to ensure that the proper amount of fluid is being removed from the patients body. Patients can read, watch television, sleep, or do other work during treatment.
Peritoneal Dialysis
Peritoneal dialysis requires the patient to play a more active role in their dialysis treatment. Of primary importance is the patient's responsibility for maintaining a clean surface on the abdomen, where treatment is administered, in order to prevent infection.
In this process, the patient weighs herself/himself to determine the fluid to be used. The patient then puts on a mask and cleans the peritoneal catheter site. Fluid that has been allowed to stay in the peritoneal cavity is drained back into the plastic bag that originally contained the fluid. The patient then disconnects this bag and connects a new bag of solution that is allowed to drain into the peritoneal cavity. Once the fluid is in the body, the new bag is rolled up and placed in the patient's underwear until the next treatment. This procedure usually takes 30 minutes to accomplish and must be done four to five times a day.
As an alternative to this treatment, some patients on peritoneal dialysis use a machine called a "cycler." This cycler is used every night. Five to six bags of dialysis fluid is used on the cycler and the machine automatically changes the fluid while the patient sleeps.
What are the advantages of the different types of dialysis?
Each of the two types of dialysis, hemodialysis and peritoneal dialysis, has advantages and disadvantages. It is up to the patient to decide which of these procedures is best by considering her/his life style, other medical conditions, support systems, and how much responsibility and participation in the treatment program he/she desires. Each patient must view the two types of dialysis procedures from her/his own perspective.
Regardless of which type of dialysis is chosen , patients have certain responsibilities such as following a diet program, watching their fluid intake and taking special vitamins and other medicines to control blood pressure and calcium and phosphorus balance.
For many patients, the major advantage of hemodialysis is minimal participation in the treatment. However, patients are required to adhere to a specific schedule and travel to the dialysis unit. Hemodialysis also requires stricter diet control and fluid control than peritoneal dialysis.
For those patients preferring more independence, peritoneal dialysis allows for more flexible scheduling and can be performed at home. The patient still must undergo a certain amount of dialysis each day, but can alter the exact timing of the dialysis procedure. On the other hand, peritoneal dialysis must be done every day of the week.
The major problem with peritoneal dialysis is infection. The patient has a plastic tube that goes from the peritoneal cavity to the outside of the body and this is a potential site for the entry of bacteria into the body. Great emphasis is placed on cleanliness and technique during the training sessions.
Indications and contraindications of dialysis
Indications for Dialysis -In Chronic Renal Failure
In patients with chronic renal failure factors to be considered before initiating dialysis should include comorbid conditions and patient preference. Timing of therapy is dictated by serum chemistries and symptoms.
A) Absolute indications
Uremic Pericarditis
Uremic Encephalopathy or Neuropathy
Pulmonary edema (unresponsive to diuretics)
Severe Hypertension
Severe hyperkalemia
Intractable acidosis
Severe Bleeding diathesis
Persistent gastrointestinal symptoms
S.Creatinine more than 12 mg/dl, BUN more than 100 mg/dl
B) Relative indications
Mild encephalopathy or neuropathy
Severe edema (unresponsive to diuretics)
Progressive gastrointestinal symptoms
Recurrent GI “itis”: stomatitis, gastritis, dudenitis, pancreatitis
Ascitis without hepatic disease
Anemia refractor to Erythropoietin
Mild Bleeding diathesis
Pruritus
Infectious complications
Depression
C) Early indications
Decrease ideal body weight
Decrease in muscle mass (decrease s creatinine or its clearance)
Decrease in s.albumin to less than 4 g/l
GFR less than 15 ml/min (by I iothalamate)
S. Creatinine >10 mg/dl and bun >100 mg /dl
Decrease in s.transferrin
Low total cholesterol
Growth retardation in children
D) Specific indications for peritoneal dialysis
Patients with cardiovascular or hemodynamic instability
Hemodialysis patients with vascular access failure or can not be created (e.g. diabetic patients)
High risk of anti coagulation
Patients in the older age group (over 65) and small children
Severe hemodialysis-related symptoms or disequilibrium
Social reason
Indications for Dialysis other than chronic renal failure
1-Acute renal failure
2-Poisons and Drug intoxication
3-Hypercalcaemia
4-Hyperuricemia
5-Hypothermia
6-Metabolic alkalosis (special dialysis solution required)
Dialyzable drugs and Poisons (partial list)
a) Barbiturates : Phenobarbital -Pentobarbital -Amobarbital
b) Alcohol's : Methanol -Ethanol -Ethylene glycol -Isopropanol
c) Analgesics : Acetylsalicylic acid -Methylsalicylate
d) Metals : Calcium -Potassium -Sodium -Lithium
e) Endogenous toxins : Uric acid -Uremic toxins -Hyperosmolar state
f) Halides : Bromide
e) Miscellaneous : Theophylline -Mannitol -Radiocontrast -Thiocynate -
Boric acid -Aniline
NB 1) Dialysis for poisoning should be considered only when supportive measures are ineffective or there is impending irreversible organ toxicity.
2) Hemoperfusion is required in some cases
Factors to be considered in determine drug’s dialyzability:
1) Dialysis related factors:
Dialyzer membrane characteristics
Surface area
Blood flow rate
Dialysate flow rate
Degree of ultrafitration
Duration of dialysis
2) Drug related factors :
Availability of the drug in the plasma
Drug pharmacokinetic characteristics
Drug molecular weight (<500 cross the membrane more readily)
Drug solubility (water soluble are dialyzable than lipid soluble)
Factors Determinants for Dialysis
Factors determining the mode of chronic dialysis should include medical and non medical factors which have an impact on the treatment modality. Physicians have the responsibility to discuss the therapeutic options and offer their advice and recommendations about the choices. In general renal transplantation should be recommended as the preferred mode of renal replacement therapy in whom surgery and immunosupression is safe and feasible.
Medical Factors
1. Age
2. Comorbid medical illnesses
3. Patient survival
4. Patient rehabilitation
5. Quality of life
Non Medical Factors
1. Government-imposed Economic limitations
2. Physician and Patient bias
3. Resource availability
4. Social ,Religious ,Cultural mores
5. Availability of transplantation
6. Family support
7. Cost , race , sex , reimbursement
Contraindications of Dialysis therapy
Principally there is no absolute contraindication to dialysis therapy. Advanced age in and of itself is not a contraindication to dialysis therapy. Many elderly are physiologically equivalent to young patients.
Relative contraindications to dialysis therapy
1. Advanced malignancy (except multiple myeloma)
2. Alzheimer’s disease
3. Multi-infarct dementia
4. Hepatorenal syndrome
5. Advanced liver cirrhosis with encephalopathy
6. Hypotension unresponsive to pressors
7. Terminal illness
8. Organic brain syndrome
Contraindication for Peritoneal dialysis
Absolute
1. Peritoneal fibrosis
2. Pleuroperitoneal leak
Relative Major
1. Chronic Ostomies
2. Severe hypercatabolic state
3. Fresh aortic prosthesis
4. Recent Abdominal surgery
5. Recent Thoracic surgery
6. Extensive Abdominal adhesions
7. Quadriplegia
8. Blindness
9. Physical handicaps
10. Mental Retardation
Relative Minor
1. Polycystic Kidney disease
2. Diverticulosis
3. Obesity
4. Peripheral vascular disease
5. Hyperlipidemia
6. Social
Introduction
Background
Chronic renal failure (CRF) requiring dialysis or transplantation is known as end-stage renal disease (ESRD). In the United States, diabetic nephropathy is the most common and hypertension the second most common cause. Along with glomerulonephritis, these cause approximately 75% of all adult cases. Certain geographic areas have a high incidence of HIV nephropathy. Genetic kidney disease such as polycystic kidney disease is a common cause in young adults.1
Patients with end-stage renal disease (ESRD) are commonly encountered in the ED with problems related to the metabolic complications of their renal disease or dialysis complications. Various problems related to vascular access in patients on hemodialysis and to abdominal catheters in patients using continuous ambulatory peritoneal dialysis (CAPD) are also common. Patients who have undergone renal transplantation may experience a variety of transplant-related conditions.
Patients with chronic renal failure often present to the ED with an unrelated condition. In these cases, the level of renal function may have important implications for diagnosis and treatment.
Pathophysiology
All major organ systems are affected by renal failure. Prevalence of symptoms is a function of the glomerular filtration rate (GFR), which averages 120 mL/min in a healthy adult. As the GFR falls to less than approximately 20% of normal, symptoms of uremia may begin to occur. They almost are invariably present when the GFR decreases to less than 10% of normal. Measuring GFR requires a timed urine collection as well as measurement of serum creatinine. However, it can be accurately estimated from a patient's age, weight, gender, and serum creatinine level. Online calculators are available to automate the calculation.2
Signs and symptoms of renal failure are due to overt metabolic derangements resulting from inability of failed kidneys to regulate electrolyte, fluid, and acid-base balance; they are also due to accumulation of toxic products of amino acid metabolism in the serum. Signs and symptoms include the following:
Systemic signs
Malaise, weakness, and fatigue are very common.
Gastrointestinal signs
GI disturbances include anorexia, nausea, vomiting, and hiccups. Peptic ulcer disease and symptomatic diverticular disease are common in patients with CRF.
Neurological signs
Peripheral neuropathy and restless legs syndrome are the most common neurologic complications of CRF. Seizures may occur due to uremia, and the prevalence of stroke is increased.
Hematologic signs
Anemia is inevitable in CRF because of loss of erythropoietin production. Abnormalities in white cell and platelet functions lead to increased susceptibility to infection and easy bruising.
Dermatologic signs
Pruritus is a common dermatologic complication assumed to be secondary to accumulation of toxic pigments (urochromes) in the dermis.
Metabolic/endocrine signs
Volume overload occurs when salt and water intake exceeds losses and excretion. This causes congestive heart failure (CHF) and exacerbates hypertension. Hyperkalemia is the most common immediately life-threatening metabolic complication of renal failure and may develop suddenly when GFR is severely reduced. Anion gap acidosis results from decreased hydrogen ion excretion and may exacerbate hyperkalemia. Hypocalcemia is potentially life threatening and results from loss of vitamin D and increased parathyroid hormone levels. Hypermagnesemia also may occur.
Cardiac signs
Volume overload may cause CHF and pulmonary edema. Hypertension contributes to cardiovascular disease. Dyslipidemia is a primary risk factor for cardiovascular disease and a common complication of ESRD. Uremia may also lead to pericardial effusion and, in rare cases, pericardial tamponade. Cardiovascular mortality is 10-20 times higher in dialysis patients than in the normal population.
Vascular signs
Vascular access complications are similar to those seen in any patient with a vascular surgical procedure (eg, bleeding, local or disseminated intravascular infections, vessel [graft] occlusion).
Dialysis catheters
A peritoneal dialysis catheter subjects patients to the risks of peritonitis and local infection. The catheter acts as a foreign body and provides a portal of entry for pathogens from the external environment.
Infection/immunologic
Patients who have received renal transplants may experience recurrent renal failure due to rejection or other graft complications. In addition, chronic immunosuppression makes them prone to infection.
Frequency
United States
The government of the United States funds treatment of end-stage renal disease (ESRD) universally for US citizens. As a consequence, the population of patients receiving dialysis or who have had a renal transplant in the United States is large. During 2004, the last year with complete data availability, 104,364 patients (approximately 0.03% of the US population) began renal replacement therapy, an adjusted incidence rate of 339 per 1,000,000. As of 2005, more than 485,000 patients were receiving treatment for ESRD in the United States. As a result, patients with ESRD are encountered on a regular basis in US emergency departments.
International
Resources allocated for treatment of ESRD vary throughout the world, and the treatments are expensive. Untreated ESRD is rapidly fatal, and treatment is too expensive for most individuals to purchase privately. Consequently, very few patients with ESRD are encountered in countries where ESRD treatment is not funded by the government.
The morbidity and mortality of dialysis patients is much higher in the United States compared with most other countries. This is probably a consequence of selection bias. Due to liberal criteria for receiving government-funded dialysis in the United States and rationing (both medical and economic) in most other countries, US patients receiving dialysis are on the average older and sicker than those in other countries.
Mortality/Morbidity
Patients in renal failure are prone to all of the complications of any underlying condition, such as diabetes and hypertension. In addition, renal failure causes a variety of metabolic and physiologic derangements.
• The most common cause of sudden death in patients with end-stage renal disease (ESRD) is hyperkalemia, which is often encountered in patients after missed dialysis or dietary indiscretion. Serum potassium also rises when the serum is acidemic, even though total body potassium is unchanged. Hyperkalemia is usually asymptomatic and should be treated empirically when suspected and when arrhythmia or cardiovascular compromise is present.
• Iatrogenic complications related to fluid administration (fluid overload) or medications are frequently encountered in patients in renal failure.
• Cardiovascular mortality is 10-20 times higher in dialysis patients than in the normal population.
• Anemia results in fatigue, reduced exercise capacity, decreased cognition, and impaired immunity.
• Renal transplant patients are prone to infection, especially in the immediate post-transplant period.
Race
Etiology of end-stage renal disease (ESRD) differs among racial groups primarily because of the prevalence of predisposing conditions, such as diabetes and hypertension. In populations with problematic access and utilization of primary medical care for treatment of predisposing conditions, ESRD often is encountered in relatively young patients. While the costs of treatment for ESRD are borne by the entire population (through government funding), relatively inexpensive preventive treatments often are funded poorly. Diseases such as diabetes and hypertension are much less likely to lead to renal failure when appropriately treated. The cost of primary care for these conditions is far lower than for dialysis or transplantation, yet primary care remains poorly funded, while ESRD treatment is reimbursed completely by the government. This conundrum is reflective of the often illogical and capricious nature of health care spending in the United States.
In the United States, racial and ethnic discrepancies in ESRD exist, with 2006 rates in the African American and Native American populations 3.6 and 1.8 times greater, respectively, than the rate among whites, and the rate in the Hispanic population 1.5 times higher than that of non-Hispanics.3
Sex
Presentation and treatment of chronic renal failure (CRF) and end-stage renal disease (ESRD) do not differ significantly between men and women. Differences in causes of renal failure are related to the types of underlying conditions prevalent in men and women.
Age
While the etiology of CRF differs among age groups, the presentations and nature of complications are similar. Young children with ESRD often are treated with transplantation rather than dialysis because of a relatively greater long-term benefit compared to that of adults, and due to difficulties related to vascular access for dialysis.
Clinical
History
Renal failure produces no symptoms early in the course of the disease. At this stage, symptoms of the underlying illness may bring the patient to medical attention and renal insufficiency is noted on laboratory testing.
• Chronic renal failure (CRF) potentially affects all organ systems. History for the presenting disorder is similar to that encountered when the same disorder exists in patients without renal failure.
• The following presentations are seen frequently in CRF. Moreover, some problems are unique to patients with CRF/ESRD; many of these are related to treatments, such as dialysis or transplantation.
• Electrolyte abnormalities include life-threatening hyperkalemia, which is usually asymptomatic.
o Dilutional hyponatremia may cause mental status changes or seizures.
o Hypocalcemia or hypermagnesemia may cause weakness and life-threatening dysrhythmias.
o Neuromuscular irritability is seen with hypocalcemia and may present as tetany or paresthesia.
o Hypermagnesemia causes neuromuscular depression with weakness and loss of reflexes.
o Acidosis may present as shortness of breath due to the work of breathing from compensatory hyperpnea.
• Pericarditis and asymptomatic pericardial effusion are common in patients with ESRD. Cardiac tamponade may occur but is rare. Presentation of pericarditis and tamponade are typical, with pleuritic chest pain being the most common presentation.
o Tamponade presents as fatigue, weakness, syncope, or dyspnea.
o Hypotension is usually present, and, if advanced, frank shock and cardiovascular collapse occur.
• Hypotension with postural weakness or syncope may occur as a complication of fluid shifts from dialysis or from any other cause. Sepsis is a serious cause of hypotension.
• Myocardial ischemia or infarction is common in patients with ESRD; consider this diagnosis in hypotensive patients along with other conditions, such as GI bleeding.
• Dialysis dysequilibrium syndrome is a common neurologic complication seen in dialysis patients.
o Syndrome is characterized by weakness, dizziness, headache, and in severe cases, mental status changes. Diagnosis is one of exclusion.
o A prime characteristic of the syndrome is that it is nonfocal.
• Peritonitis is common in patients being treated with continuous ambulatory peritoneal dialysis (CAPD), occurring approximately once per patient year. Patients present with abdominal pain, which may be mild, or complain of a cloudy effluent. Fever often is absent.
• Infection at the catheter exit site manifests as expected local pain, erythema, warmth, and/or fluctuance.
• Other abdominal conditions, such as appendicitis, pancreatitis, or diverticulitis, should be considered when patients present with abdominal pain, especially if signs and symptoms are localized.
• Vascular access problems include infections, which are usually manifest with typical signs and symptoms such as local pain, redness, warmth, or fluctuance. Fever may be present without local signs.
o Clotting of the vascular access presents as loss of normal bruit or thrill. There may be signs or symptoms of distal limb ischemia.
o Patients may present after dialysis or minor trauma with bleeding from their vascular access. Bleeding usually can be controlled with elevation and firm but nonocclusive pressure. In the immediate postdialysis period, protamine may be needed to reverse the effect of heparin (routinely used in dialysis to prevent clotting). Life-threatening bleeding may occur.
Physical
• Chronic renal failure (CRF) produces no specific physical findings.
• Patients with an arteriovenous fistula or graft should have the site examined regularly. Abnormal findings include loss of palpable thrill, overlying erythema, or active bleeding from the incisional wound of a newly placed fistula or graft.
• Physical findings of chronic renal failure complications generally are those expected with the specific complication and do not differ from those encountered when the condition occurs in patients with normal renal function.
• Certain complications are very common in renal failure.
• CAPD-associated peritonitis
o Abdominal pain and tenderness usually are generalized and relatively mild.
o Localized pain and tenderness suggest a local process, such as incarcerated hernia or appendicitis.
o Severe generalized peritonitis may be due to a perforated viscus as in any other patient.
• Transplant-related problems: Pain and tenderness over a transplanted kidney may be due to infection (pyelonephritis), obstruction (stone or extrinsic compression), or graft rejection.
• Vascular access aneurysms or pseudoaneurysms : These present as localized swelling, which may be pulsatile, and are often chronic. A rapid increase in size may indicate active bleeding.
Causes
Once chronic renal failure (CRF) has occurred, treatment options and complications are largely independent of the cause.
• In terms of broad categories of disease, glomerulonephritis and interstitial nephritis are the most common causes of CRF in adults and children.
• Chronic upper urinary tract infection causes CRF in all age groups.
• CRF also is encountered in children because of congenital anomalies such as chronic hydronephrosis, which is caused by anatomic defects that obstruct urine flow or allow reflux from the bladder (vesicoureteral reflux).
• Kidneys may be congenitally hypoplastic.
• Hereditary nephropathies also exist.
• In adults, diabetic and hypertensive nephropathies are the most common specific causes of CRF.
• Polycystic disease, renal vascular disease, and analgesic nephropathy also are common.
• In certain geographic areas, HIV-related renal disease is becoming common.
• Certain diseases such as some of the types of glomerulonephritis tend to recur in transplanted kidneys. In these cases, dialysis is the preferred treatment option.
• Consider renal transplant patients to be mildly to moderately immunosuppressed.
o In the immediate posttransplant period or during a rejection episode, intensive immunosuppression puts patients at considerable risk of infection, including disseminated viral infections such as herpes zoster.
o Degree of immunosuppression is less late in the posttransplant course when corticosteroids alone may be used.
What is dialysis?
The kidneys are responsible for filtering waste products from the blood. Dialysis is a procedure that is a substitute for many of the normal duties of the kidneys. The kidneys are two organs located on either side of the back of the abdominal cavity. Dialysis can allow individuals to live productive and useful lives, even though their kidneys no longer work adequately. In the United States, there are over 200,000 people who use dialysis techniques on an ongoing basis.
Dialysis helps the body by performing the functions of failed kidneys. The kidney has many roles. An essential job of the kidney is to regulate the body's fluid balance. It does this by adjusting the amount of urine that is excreted on a daily basis. On hot days, the body sweats more. Thus, less water needs to be excreted through the kidneys. On cold days, the body sweats less. Thus, urine output needs to be greater in order to maintain the proper balance within the body. It is the kidney's job to regulate fluid balance by adjusting urine output.
Another major duty of the kidney is to remove the waste products that the body produces throughout the day. As the body functions, the cells use energy. The operation of the cells produces waste products that must be removed from the body. When these waste products are not removed adequately, they build up in the body. An elevation of waste products, as measured in the blood, is called "azotemia." When waste products accumulate they, cause a sick feeling throughout the body called "uremia."
When do patients require dialysis?
Patients usually require dialysis when the waste products in their body become so high that they start to become sick from them. The level of the waste products usually builds up slowly. Doctors measure several blood chemical levels to help decide when dialysis is necessary. The two major blood chemical levels that are measured are the "creatinine level" and the "blood urea nitrogen" (BUN) level. As these two levels rise, they are indicators of the decreasing ability of the kidneys to cleanse the body of waste products.
Doctors use a urine test, the "creatinine clearance," to measure the level of kidney function. The patient saves urine in a special container for one full day. The waste products in the urine and in the blood are estimated by measuring the creatinine. By comparing the blood and urine level of this substance, the doctor has an accurate idea of how well the kidneys are working. This result is called the creatinine clearance. Usually, when the creatinine clearance falls to 10-12 cc/minute, the patient needs dialysis.
The doctor uses other indicators of the patient's status to decide about the need for dialysis. If the patient is experiencing a major inability to rid the body of excess water, or is complaining of problems with the heart, lungs, or stomach, or difficulties with taste or sensation in their legs, dialysis may be indicated even though the creatinine clearance has not fallen to the 10-12 cc/minute level.
What types of dialysis are there?
There are two main types of dialysis: "hemodialysis" and "peritoneal dialysis." Hemodialysis uses a special type of filter to remove excess waste products and water from the body. Peritoneal dialysis uses a fluid that is placed into the patient's stomach cavity through a special plastic tube to remove excess waste products and fluid from the body.
During Hemodialysis, blood passes from the patient's body through a filter in the dialysis machine, called a "dialysis membrane." For this procedure, the patient has a specialized plastic tube placed between an artery and a vein in the arm or leg (called a "gortex graft"). Sometimes, a direct connection is made between an artery and a vein in the arm. This procedure is called a "Cimino fistula." Needles are then placed in the graft or fistula, and blood passes to the dialysis machine, through the filter, and back to the patient. In the dialysis machine, a solution on the other side of the filter receives the waste products from the patient.
Peritoneal dialysis uses the patients own body tissues inside of the belly (abdominal cavity) to act as the filter. The intestines lie in the abdominal cavity, the space between the abdominal wall and the spine. A plastic tube called a "dialysis catheter" is placed through the abdominal wall into the abdominal cavity. A special fluid is then flushed into the abdominal cavity and washes around the intestines. The intestinal walls act as a filter between this fluid and the blood stream. By using different types of solutions, waste products and excess water can be removed from the body through this process.
What does the patient do during dialysis?
Hemodialysis
Treatment for hemodialysis takes place in a hemodialysis unit. This is a special building that is equipped with machines that perform the dialysis treatment. Special equipment adds the proper materials to purified water for the dialysis machines. The dialysis unit is also the place where patients can receive dietary counseling and help with social needs.
Patients generally go to the dialysis unit three times a week for treatment. For example, the schedule is either on Monday, Wednesday, and Friday or Tuesday, Thursday, and Saturday. Before treatment, patients weigh themselves so that excess fluid accumulated since the last dialysis session can be measured. Patients then go to assigned chairs that are like lounge chairs. The area of the graft or fistula (the connection between the artery and vein), is cleaned thoroughly. Two needles are then inserted into the graft or fistula. One takes the blood to the machine where it is cleaned. The other needle allows blood that is returning to the patient to go back into the patient's body.
Treatments last from 2 ½ to 4 ½ hours. During this time, the dialysis staff checks the patient's blood pressure frequently and adjusts the dialysis machine to ensure that the proper amount of fluid is being removed from the patients body. Patients can read, watch television, sleep, or do other work during treatment.
Peritoneal Dialysis
Peritoneal dialysis requires the patient to play a more active role in their dialysis treatment. Of primary importance is the patient's responsibility for maintaining a clean surface on the abdomen, where treatment is administered, in order to prevent infection.
In this process, the patient weighs herself/himself to determine the fluid to be used. The patient then puts on a mask and cleans the peritoneal catheter site. Fluid that has been allowed to stay in the peritoneal cavity is drained back into the plastic bag that originally contained the fluid. The patient then disconnects this bag and connects a new bag of solution that is allowed to drain into the peritoneal cavity. Once the fluid is in the body, the new bag is rolled up and placed in the patient's underwear until the next treatment. This procedure usually takes 30 minutes to accomplish and must be done four to five times a day.
As an alternative to this treatment, some patients on peritoneal dialysis use a machine called a "cycler." This cycler is used every night. Five to six bags of dialysis fluid is used on the cycler and the machine automatically changes the fluid while the patient sleeps.
What are the advantages of the different types of dialysis?
Each of the two types of dialysis, hemodialysis and peritoneal dialysis, has advantages and disadvantages. It is up to the patient to decide which of these procedures is best by considering her/his life style, other medical conditions, support systems, and how much responsibility and participation in the treatment program he/she desires. Each patient must view the two types of dialysis procedures from her/his own perspective.
Regardless of which type of dialysis is chosen , patients have certain responsibilities such as following a diet program, watching their fluid intake and taking special vitamins and other medicines to control blood pressure and calcium and phosphorus balance.
For many patients, the major advantage of hemodialysis is minimal participation in the treatment. However, patients are required to adhere to a specific schedule and travel to the dialysis unit. Hemodialysis also requires stricter diet control and fluid control than peritoneal dialysis.
For those patients preferring more independence, peritoneal dialysis allows for more flexible scheduling and can be performed at home. The patient still must undergo a certain amount of dialysis each day, but can alter the exact timing of the dialysis procedure. On the other hand, peritoneal dialysis must be done every day of the week.
The major problem with peritoneal dialysis is infection. The patient has a plastic tube that goes from the peritoneal cavity to the outside of the body and this is a potential site for the entry of bacteria into the body. Great emphasis is placed on cleanliness and technique during the training sessions.
Indications and contraindications of dialysis
Indications for Dialysis -In Chronic Renal Failure
In patients with chronic renal failure factors to be considered before initiating dialysis should include comorbid conditions and patient preference. Timing of therapy is dictated by serum chemistries and symptoms.
A) Absolute indications
Uremic Pericarditis
Uremic Encephalopathy or Neuropathy
Pulmonary edema (unresponsive to diuretics)
Severe Hypertension
Severe hyperkalemia
Intractable acidosis
Severe Bleeding diathesis
Persistent gastrointestinal symptoms
S.Creatinine more than 12 mg/dl, BUN more than 100 mg/dl
B) Relative indications
Mild encephalopathy or neuropathy
Severe edema (unresponsive to diuretics)
Progressive gastrointestinal symptoms
Recurrent GI “itis”: stomatitis, gastritis, dudenitis, pancreatitis
Ascitis without hepatic disease
Anemia refractor to Erythropoietin
Mild Bleeding diathesis
Pruritus
Infectious complications
Depression
C) Early indications
Decrease ideal body weight
Decrease in muscle mass (decrease s creatinine or its clearance)
Decrease in s.albumin to less than 4 g/l
GFR less than 15 ml/min (by I iothalamate)
S. Creatinine >10 mg/dl and bun >100 mg /dl
Decrease in s.transferrin
Low total cholesterol
Growth retardation in children
D) Specific indications for peritoneal dialysis
Patients with cardiovascular or hemodynamic instability
Hemodialysis patients with vascular access failure or can not be created (e.g. diabetic patients)
High risk of anti coagulation
Patients in the older age group (over 65) and small children
Severe hemodialysis-related symptoms or disequilibrium
Social reason
Indications for Dialysis other than chronic renal failure
1-Acute renal failure
2-Poisons and Drug intoxication
3-Hypercalcaemia
4-Hyperuricemia
5-Hypothermia
6-Metabolic alkalosis (special dialysis solution required)
Dialyzable drugs and Poisons (partial list)
a) Barbiturates : Phenobarbital -Pentobarbital -Amobarbital
b) Alcohol's : Methanol -Ethanol -Ethylene glycol -Isopropanol
c) Analgesics : Acetylsalicylic acid -Methylsalicylate
d) Metals : Calcium -Potassium -Sodium -Lithium
e) Endogenous toxins : Uric acid -Uremic toxins -Hyperosmolar state
f) Halides : Bromide
e) Miscellaneous : Theophylline -Mannitol -Radiocontrast -Thiocynate -
Boric acid -Aniline
NB 1) Dialysis for poisoning should be considered only when supportive measures are ineffective or there is impending irreversible organ toxicity.
2) Hemoperfusion is required in some cases
Factors to be considered in determine drug’s dialyzability:
1) Dialysis related factors:
Dialyzer membrane characteristics
Surface area
Blood flow rate
Dialysate flow rate
Degree of ultrafitration
Duration of dialysis
2) Drug related factors :
Availability of the drug in the plasma
Drug pharmacokinetic characteristics
Drug molecular weight (<500 cross the membrane more readily)
Drug solubility (water soluble are dialyzable than lipid soluble)
Factors Determinants for Dialysis
Factors determining the mode of chronic dialysis should include medical and non medical factors which have an impact on the treatment modality. Physicians have the responsibility to discuss the therapeutic options and offer their advice and recommendations about the choices. In general renal transplantation should be recommended as the preferred mode of renal replacement therapy in whom surgery and immunosupression is safe and feasible.
Medical Factors
1. Age
2. Comorbid medical illnesses
3. Patient survival
4. Patient rehabilitation
5. Quality of life
Non Medical Factors
1. Government-imposed Economic limitations
2. Physician and Patient bias
3. Resource availability
4. Social ,Religious ,Cultural mores
5. Availability of transplantation
6. Family support
7. Cost , race , sex , reimbursement
Contraindications of Dialysis therapy
Principally there is no absolute contraindication to dialysis therapy. Advanced age in and of itself is not a contraindication to dialysis therapy. Many elderly are physiologically equivalent to young patients.
Relative contraindications to dialysis therapy
1. Advanced malignancy (except multiple myeloma)
2. Alzheimer’s disease
3. Multi-infarct dementia
4. Hepatorenal syndrome
5. Advanced liver cirrhosis with encephalopathy
6. Hypotension unresponsive to pressors
7. Terminal illness
8. Organic brain syndrome
Contraindication for Peritoneal dialysis
Absolute
1. Peritoneal fibrosis
2. Pleuroperitoneal leak
Relative Major
1. Chronic Ostomies
2. Severe hypercatabolic state
3. Fresh aortic prosthesis
4. Recent Abdominal surgery
5. Recent Thoracic surgery
6. Extensive Abdominal adhesions
7. Quadriplegia
8. Blindness
9. Physical handicaps
10. Mental Retardation
Relative Minor
1. Polycystic Kidney disease
2. Diverticulosis
3. Obesity
4. Peripheral vascular disease
5. Hyperlipidemia
6. Social
Introduction
Background
Chronic renal failure (CRF) requiring dialysis or transplantation is known as end-stage renal disease (ESRD). In the United States, diabetic nephropathy is the most common and hypertension the second most common cause. Along with glomerulonephritis, these cause approximately 75% of all adult cases. Certain geographic areas have a high incidence of HIV nephropathy. Genetic kidney disease such as polycystic kidney disease is a common cause in young adults.1
Patients with end-stage renal disease (ESRD) are commonly encountered in the ED with problems related to the metabolic complications of their renal disease or dialysis complications. Various problems related to vascular access in patients on hemodialysis and to abdominal catheters in patients using continuous ambulatory peritoneal dialysis (CAPD) are also common. Patients who have undergone renal transplantation may experience a variety of transplant-related conditions.
Patients with chronic renal failure often present to the ED with an unrelated condition. In these cases, the level of renal function may have important implications for diagnosis and treatment.
Pathophysiology
All major organ systems are affected by renal failure. Prevalence of symptoms is a function of the glomerular filtration rate (GFR), which averages 120 mL/min in a healthy adult. As the GFR falls to less than approximately 20% of normal, symptoms of uremia may begin to occur. They almost are invariably present when the GFR decreases to less than 10% of normal. Measuring GFR requires a timed urine collection as well as measurement of serum creatinine. However, it can be accurately estimated from a patient's age, weight, gender, and serum creatinine level. Online calculators are available to automate the calculation.2
Signs and symptoms of renal failure are due to overt metabolic derangements resulting from inability of failed kidneys to regulate electrolyte, fluid, and acid-base balance; they are also due to accumulation of toxic products of amino acid metabolism in the serum. Signs and symptoms include the following:
Systemic signs
Malaise, weakness, and fatigue are very common.
Gastrointestinal signs
GI disturbances include anorexia, nausea, vomiting, and hiccups. Peptic ulcer disease and symptomatic diverticular disease are common in patients with CRF.
Neurological signs
Peripheral neuropathy and restless legs syndrome are the most common neurologic complications of CRF. Seizures may occur due to uremia, and the prevalence of stroke is increased.
Hematologic signs
Anemia is inevitable in CRF because of loss of erythropoietin production. Abnormalities in white cell and platelet functions lead to increased susceptibility to infection and easy bruising.
Dermatologic signs
Pruritus is a common dermatologic complication assumed to be secondary to accumulation of toxic pigments (urochromes) in the dermis.
Metabolic/endocrine signs
Volume overload occurs when salt and water intake exceeds losses and excretion. This causes congestive heart failure (CHF) and exacerbates hypertension. Hyperkalemia is the most common immediately life-threatening metabolic complication of renal failure and may develop suddenly when GFR is severely reduced. Anion gap acidosis results from decreased hydrogen ion excretion and may exacerbate hyperkalemia. Hypocalcemia is potentially life threatening and results from loss of vitamin D and increased parathyroid hormone levels. Hypermagnesemia also may occur.
Cardiac signs
Volume overload may cause CHF and pulmonary edema. Hypertension contributes to cardiovascular disease. Dyslipidemia is a primary risk factor for cardiovascular disease and a common complication of ESRD. Uremia may also lead to pericardial effusion and, in rare cases, pericardial tamponade. Cardiovascular mortality is 10-20 times higher in dialysis patients than in the normal population.
Vascular signs
Vascular access complications are similar to those seen in any patient with a vascular surgical procedure (eg, bleeding, local or disseminated intravascular infections, vessel [graft] occlusion).
Dialysis catheters
A peritoneal dialysis catheter subjects patients to the risks of peritonitis and local infection. The catheter acts as a foreign body and provides a portal of entry for pathogens from the external environment.
Infection/immunologic
Patients who have received renal transplants may experience recurrent renal failure due to rejection or other graft complications. In addition, chronic immunosuppression makes them prone to infection.
Frequency
United States
The government of the United States funds treatment of end-stage renal disease (ESRD) universally for US citizens. As a consequence, the population of patients receiving dialysis or who have had a renal transplant in the United States is large. During 2004, the last year with complete data availability, 104,364 patients (approximately 0.03% of the US population) began renal replacement therapy, an adjusted incidence rate of 339 per 1,000,000. As of 2005, more than 485,000 patients were receiving treatment for ESRD in the United States. As a result, patients with ESRD are encountered on a regular basis in US emergency departments.
International
Resources allocated for treatment of ESRD vary throughout the world, and the treatments are expensive. Untreated ESRD is rapidly fatal, and treatment is too expensive for most individuals to purchase privately. Consequently, very few patients with ESRD are encountered in countries where ESRD treatment is not funded by the government.
The morbidity and mortality of dialysis patients is much higher in the United States compared with most other countries. This is probably a consequence of selection bias. Due to liberal criteria for receiving government-funded dialysis in the United States and rationing (both medical and economic) in most other countries, US patients receiving dialysis are on the average older and sicker than those in other countries.
Mortality/Morbidity
Patients in renal failure are prone to all of the complications of any underlying condition, such as diabetes and hypertension. In addition, renal failure causes a variety of metabolic and physiologic derangements.
• The most common cause of sudden death in patients with end-stage renal disease (ESRD) is hyperkalemia, which is often encountered in patients after missed dialysis or dietary indiscretion. Serum potassium also rises when the serum is acidemic, even though total body potassium is unchanged. Hyperkalemia is usually asymptomatic and should be treated empirically when suspected and when arrhythmia or cardiovascular compromise is present.
• Iatrogenic complications related to fluid administration (fluid overload) or medications are frequently encountered in patients in renal failure.
• Cardiovascular mortality is 10-20 times higher in dialysis patients than in the normal population.
• Anemia results in fatigue, reduced exercise capacity, decreased cognition, and impaired immunity.
• Renal transplant patients are prone to infection, especially in the immediate post-transplant period.
Race
Etiology of end-stage renal disease (ESRD) differs among racial groups primarily because of the prevalence of predisposing conditions, such as diabetes and hypertension. In populations with problematic access and utilization of primary medical care for treatment of predisposing conditions, ESRD often is encountered in relatively young patients. While the costs of treatment for ESRD are borne by the entire population (through government funding), relatively inexpensive preventive treatments often are funded poorly. Diseases such as diabetes and hypertension are much less likely to lead to renal failure when appropriately treated. The cost of primary care for these conditions is far lower than for dialysis or transplantation, yet primary care remains poorly funded, while ESRD treatment is reimbursed completely by the government. This conundrum is reflective of the often illogical and capricious nature of health care spending in the United States.
In the United States, racial and ethnic discrepancies in ESRD exist, with 2006 rates in the African American and Native American populations 3.6 and 1.8 times greater, respectively, than the rate among whites, and the rate in the Hispanic population 1.5 times higher than that of non-Hispanics.3
Sex
Presentation and treatment of chronic renal failure (CRF) and end-stage renal disease (ESRD) do not differ significantly between men and women. Differences in causes of renal failure are related to the types of underlying conditions prevalent in men and women.
Age
While the etiology of CRF differs among age groups, the presentations and nature of complications are similar. Young children with ESRD often are treated with transplantation rather than dialysis because of a relatively greater long-term benefit compared to that of adults, and due to difficulties related to vascular access for dialysis.
Clinical
History
Renal failure produces no symptoms early in the course of the disease. At this stage, symptoms of the underlying illness may bring the patient to medical attention and renal insufficiency is noted on laboratory testing.
• Chronic renal failure (CRF) potentially affects all organ systems. History for the presenting disorder is similar to that encountered when the same disorder exists in patients without renal failure.
• The following presentations are seen frequently in CRF. Moreover, some problems are unique to patients with CRF/ESRD; many of these are related to treatments, such as dialysis or transplantation.
• Electrolyte abnormalities include life-threatening hyperkalemia, which is usually asymptomatic.
o Dilutional hyponatremia may cause mental status changes or seizures.
o Hypocalcemia or hypermagnesemia may cause weakness and life-threatening dysrhythmias.
o Neuromuscular irritability is seen with hypocalcemia and may present as tetany or paresthesia.
o Hypermagnesemia causes neuromuscular depression with weakness and loss of reflexes.
o Acidosis may present as shortness of breath due to the work of breathing from compensatory hyperpnea.
• Pericarditis and asymptomatic pericardial effusion are common in patients with ESRD. Cardiac tamponade may occur but is rare. Presentation of pericarditis and tamponade are typical, with pleuritic chest pain being the most common presentation.
o Tamponade presents as fatigue, weakness, syncope, or dyspnea.
o Hypotension is usually present, and, if advanced, frank shock and cardiovascular collapse occur.
• Hypotension with postural weakness or syncope may occur as a complication of fluid shifts from dialysis or from any other cause. Sepsis is a serious cause of hypotension.
• Myocardial ischemia or infarction is common in patients with ESRD; consider this diagnosis in hypotensive patients along with other conditions, such as GI bleeding.
• Dialysis dysequilibrium syndrome is a common neurologic complication seen in dialysis patients.
o Syndrome is characterized by weakness, dizziness, headache, and in severe cases, mental status changes. Diagnosis is one of exclusion.
o A prime characteristic of the syndrome is that it is nonfocal.
• Peritonitis is common in patients being treated with continuous ambulatory peritoneal dialysis (CAPD), occurring approximately once per patient year. Patients present with abdominal pain, which may be mild, or complain of a cloudy effluent. Fever often is absent.
• Infection at the catheter exit site manifests as expected local pain, erythema, warmth, and/or fluctuance.
• Other abdominal conditions, such as appendicitis, pancreatitis, or diverticulitis, should be considered when patients present with abdominal pain, especially if signs and symptoms are localized.
• Vascular access problems include infections, which are usually manifest with typical signs and symptoms such as local pain, redness, warmth, or fluctuance. Fever may be present without local signs.
o Clotting of the vascular access presents as loss of normal bruit or thrill. There may be signs or symptoms of distal limb ischemia.
o Patients may present after dialysis or minor trauma with bleeding from their vascular access. Bleeding usually can be controlled with elevation and firm but nonocclusive pressure. In the immediate postdialysis period, protamine may be needed to reverse the effect of heparin (routinely used in dialysis to prevent clotting). Life-threatening bleeding may occur.
Physical
• Chronic renal failure (CRF) produces no specific physical findings.
• Patients with an arteriovenous fistula or graft should have the site examined regularly. Abnormal findings include loss of palpable thrill, overlying erythema, or active bleeding from the incisional wound of a newly placed fistula or graft.
• Physical findings of chronic renal failure complications generally are those expected with the specific complication and do not differ from those encountered when the condition occurs in patients with normal renal function.
• Certain complications are very common in renal failure.
• CAPD-associated peritonitis
o Abdominal pain and tenderness usually are generalized and relatively mild.
o Localized pain and tenderness suggest a local process, such as incarcerated hernia or appendicitis.
o Severe generalized peritonitis may be due to a perforated viscus as in any other patient.
• Transplant-related problems: Pain and tenderness over a transplanted kidney may be due to infection (pyelonephritis), obstruction (stone or extrinsic compression), or graft rejection.
• Vascular access aneurysms or pseudoaneurysms : These present as localized swelling, which may be pulsatile, and are often chronic. A rapid increase in size may indicate active bleeding.
Causes
Once chronic renal failure (CRF) has occurred, treatment options and complications are largely independent of the cause.
• In terms of broad categories of disease, glomerulonephritis and interstitial nephritis are the most common causes of CRF in adults and children.
• Chronic upper urinary tract infection causes CRF in all age groups.
• CRF also is encountered in children because of congenital anomalies such as chronic hydronephrosis, which is caused by anatomic defects that obstruct urine flow or allow reflux from the bladder (vesicoureteral reflux).
• Kidneys may be congenitally hypoplastic.
• Hereditary nephropathies also exist.
• In adults, diabetic and hypertensive nephropathies are the most common specific causes of CRF.
• Polycystic disease, renal vascular disease, and analgesic nephropathy also are common.
• In certain geographic areas, HIV-related renal disease is becoming common.
• Certain diseases such as some of the types of glomerulonephritis tend to recur in transplanted kidneys. In these cases, dialysis is the preferred treatment option.
• Consider renal transplant patients to be mildly to moderately immunosuppressed.
o In the immediate posttransplant period or during a rejection episode, intensive immunosuppression puts patients at considerable risk of infection, including disseminated viral infections such as herpes zoster.
o Degree of immunosuppression is less late in the posttransplant course when corticosteroids alone may be used.
Glycogen storage disease type II (Pompe Disease)
Glycogen storage disease type II (Pompe Disease)
Glycogen storage disease type II (also called Pompe disease or acid maltase deficiency) is an autosomal recessive metabolic disorder[1] which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme. It is the only glycogen storage disease with a defect in lysosomal metabolism, and the first glycogen storage disease to be identified, in 1932.
The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.
Glycogen storage disease type II
Classification and external resources
ICD-10
E74.0
ICD-9
271.0
OMIM
232300
DiseasesDB
5296
eMedicine
med/908 ped/1866
MeSH
D006009
Variants
Pompe disease has historically been divided into three forms defined by age of onset and progression of symptoms (see below). More recently there has been a trend to divide the disease into two groups: infantile onset (involving the massive enlargement of the heart) and late onset (no heart enlargement).[citation needed]
Infantile, or early onset, is noticed shortly after birth. Symptoms include severe lack of muscle tone, weakness, an enlarged liver (hepatomegaly), and an enlarged heart (cardiomegaly).[citation needed] Mental function is not affected. Development appears normal for the first weeks or months but slowly declines as the disease progresses. Swallowing may become difficult and the tongue may protrude and become enlarged. Most children die from respiratory or cardiac complications before 2 years of age.[citation needed]
Juvenile onset symptoms appear in early to late childhood and include progressive weakness of respiratory muscles in the trunk, diaphragm and lower limbs, as well as exercise intolerance. Intelligence is normal.[citation needed]
Adult onset symptoms also involve generalized muscle weakness and wasting of respiratory muscles in the trunk, lower limbs, and diaphragm. Many patients report respiratory distress, headache at night or upon waking, diminished deep tendon reflexes, and proximal muscle weakness, such as difficulty in climbing stairs. Intellect is not affected. A small number of adult patients live without major symptoms or limitations.[citation needed]
Pompe's disease is one of the infiltrative causes of restrictive cardiomyopathy.[citation needed]
Treatment
Cardiac and respiratory complications are treated symptomatically. Physical and occupational therapy may be beneficial for some patients. Alterations in diet may provide temporary improvement but will not alter the course of the disease.[citation needed] Genetic counseling can provide families with information regarding risk in future pregnancies.
On April 28, 2006 the US Food and Drug Administration approved a biologics license application (BLA) for Myozyme (alglucosidase alfa, rhGAA),[2] the first treatment for patients with Pompe disease. This was based on enzyme replacement therapy work pioneered by Drs Arnold Reuser and Ans van der Ploeg at Erasmus University, Rotterdam.[3] Myozyme falls under the FDA Orphan Drug designation and was approved under a priority review.
The currently approved Myozyme is manufactured by Genzyme Corp. in Cambridge, Massachusetts, USA. Its development was a complex process. Genzyme first partnered with Pharming Group NV who had managed to produce acid alpha-glucosidase from the milk of transgentic rabbits. They also partnered with a second group based at Duke University using Chinese hamster ovary cells. In 2001 it acquired Novazyme which was also working on this enzyme. Genzyme also had its own product (Myozyme) under development. In November 2001 Genzyme chief executive Henri Termeer organised a systematic comparison of the various potential drugs in transgenic mice. It was found that Myozyme was the most efficatious and easiest to manufacture. Work on the other products was then discontinued.
The FDA has approved Myozyme for administration by intravenous infusion of solution into a vein. The safety and efficacy of Myozyme were assessed in two separate clinical trials in 39 infantile-onset patients with Pompe disease ranging in age from 1 month to 3.5 years at the time of the first infusion. Myozyme costs an average of $300,000 a year, and must be taken for the patients' entire life. The treatment is not without side effects which include fever, cardiac failure, pneumonia, respiratory failure and rarely shock. Some insurers have refused to pay for it.[4] The treatment is better at stabilizing the clinical condition than reversing the pathological changes that have already occurred. Early diagnosis leads to better outcomes.
On August 14, 2006, Health Canada approved Myozyme for the treatment of Pompe disease. On June 14, 2007 the Canadian Common Drug Review issued their recommendations regarding public funding for Myozyme therapy. Their recommendation was to provide funding to treat a very small subset of Pompe patients (Infants less one year of age with Cardiomyopathy).[5] The vast majority of developed countries are providing access to therapy for all diagnosed Pompe patients.[6]
In June 2007 it was reported that ZyStor Therapeutics was in the process of developing an enzyme replacement therapy for Pompe disease by leveraging their glycosylation independent lysosomal targeting technology (GILT).[7]
Prognosis
The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. Without treatment the disease is particularly lethal in infants and young children.
Myozyme (alglucosidase alfa), which helps break down glucose, is a combined form of the human enzyme acid alpha-glucosidase, and is also currently being used to replace the missing enzyme. In a study[8] which included the largest cohort of patients with Pompe disease treated with enzyme replacement therapy (ERT) to date findings showed that Myozyme treatment clearly prolongs ventilator-free survival and overall survival in patients with infantile-onset Pompe disease as compared to an untreated historical control population. Furthermore, the study demonstrated that initiation of ERT prior to 6 months of age, which could be facilitated by newborn screening, shows great promise to reduce the mortality and disability associated with this devastating disorder.
On December 13, 2007, Genzyme released the initial results of its Late Onset Treatment Study (LOTS). The study was undertaken to evaluate the safety and efficacy of Myozyme in juvenile and adult patients with Pompe disease. LOTS was a randomized, double-blind, placebo-controlled study that enrolled 90 patients at eight primary sites in the United States and Europe. Participants received either Myozyme or a placebo every other week for 18 months. The average age of study participants was 44 years. The primary efficacy endpoints of the study sought to determine the effect of Myozyme on functional endurance as measured by the six-minute walk test and to determine the effect of Myozyme on pulmonary function as measured by percent predicted forced vital capacity.
The results showed that, at 18 months, patients treated with Myozyme increased their distance walked in six minutes by an average of approximately 30 meters as compared with the placebo group (P=0.0283; Wilcoxon test). The placebo group did not show any improvement from baseline. The average baseline distance walked in six minutes in both groups was approximately 325 meters. Percent predicted forced vital capacity in the group of patients treated with Myozyme increased by 1 percent at 18 months. In contrast, it declined by approximately 3 percent in the placebo group (P=0.0026; Wilcoxon test). The average baseline percent predicted forced vital capacity in both groups was approximately 55 percent.
The results for both efficacy endpoints were consistent across various prospectively defined subgroups.
Epidemiology
Glycogen storage disease type II has an autosomal recessive pattern of inheritance.
The disorder is estimated to occur in about 1 in 40,000 births. Worldwide there are thought to be about 5,000 to 10,000 suffers of this disease.
It has an autosomal recessive inheritance pattern. This means the defective gene is located on an autosome, and two copies of the gene—one from each parent—are required to be born with the disorder. As with all cases of autosomal recessive inheritance, children have a 1 in 4 chance of inheriting the disorder when both parents carry the defective gene, and although both parents carry one copy of the defective gene, they are usually not affected by the disorder.
History
The disease is named after Johann Pompe, who characterized it in 1932.[9][10] Pompe described accumulation of glycogen in muscle tissue in some cases of a previously unknown disorder. This accumulation was difficult to explain as the enzymes involved in the usual metabolism of glucose and glycogen were all present and functioning.
The basis for the disease remained a puzzle until Christian de Duve's discovery of lysosomes in 1955 for which he won the Nobel Prize in 1974. His co-worker Henri G. Hers realised in 1965 that the deficiency of a lysosomal enzyme (alpha glucosidase) for the breakdown of glycogen could explain the symptoms of Pompe disease. This discovery lead to establishing the concept of lysosomal storage diseases of which 49 have been described (to date).
Despite recognizing the basis for the disease treatment proved difficult. Administration of the enzyme lead to its uptake by the liver and not the muscle cells where it is needed. Despite this work at Erasmus MC University Medical Center, Rotterdam began in the '70s. In the early 1990s two Dutch scientists, Arnold Reuser and Ans van der Ploeg a PhD student, had the idea that phosphorylated enzyme would be taken via by the mannose-6-phosphate receptors in lysosomes thus allowing the enzyme to be targeted. Using alpha-glucosidase containing phosphorylated mannose residues they were able to show that an increase in the enzyme's activity in the muscles.[11] The increases reported - 43% increase in skeletal muscle and 70% in the heart - were likely to be clinically significant.
They cloned the acid alpha-glucosidase gene and then made the first mouse model of Pompe's disease. A second model was developed by Yuan-Tsong Chen and colleagues at Duke University using the quail. (Dr. Chen is the director of the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.) The results of the work at Dukes were impressive with one treated animal recovering to the point of being able to fly again.[12]
This was followed by production of alpha-glucosidase in Chinese hamster ovary (CHO) cells and in the milk of transgenic rabbits.[13] This work eventually culminated in the start of clinical trials with the first clinical trial including 4 babies taking place at Erasmus MC Sophia Children’s Hospital in 1999. This was organised by Pharming in the Netherlands. A second trial in 2001 organised by Dr Chen and Synpac, a Taiwan-based company, used enzyme grown in CHO cells[14] (陳垣崇) while he was at Duke University. Both trials were successful.
Genzyme which had an existing enzyme replacement therapy for Gaucher's disease became involved at this point. They developed a product of their own for Pompe's disease also grown in CHO cells. This is now marketed as Myozyme.
Much of the funding for research in this field was provided by the Association of Glycogen Storage Disorders. This association was founded by a Scotsman - Kevin O’Donnell - whose son Calum aged eight months died from Pompe's disease in 1993. A grant from the AGSD-UK in 1996 funded the work that showed that replacement treatment could work. A second fund-raising group was formed in 1999 - the International Pompe Association.
John Crowley became involved in the fund-raising efforts in 1998 after two of his children were diagnosed with Pompe's. He joined the company Novazyme in 1999 which was working on enzyme replacement treatment for Pompe's. Novazyme was sold to Genzyme in 2001 for over US$100 million.
[hide]
v • d • e
Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders (including glycogen storage diseases) (E73-74, 271)
Sucrose, transport
(extracellular) Disaccharide catabolism Lactose intolerance • Sucrose intolerance
Monosaccharide transport Glucose-galactose malabsorption • Inborn errors of renal tubular transport (Renal glycosuria) • Fructose malabsorption
Hexose → glucose
Monosaccharide catabolism fructose: Essential fructosuria • Fructose intolerance
galactose/galactosemia : GALK deficiency • GALT deficiency/GALE deficiency
Glucose ⇄ glycogen
Glycogenesis
GSD type 0, glycogen synthase • GSD type IV, Andersen's, branching
Glycogenolysis
extralysosomal: GSD type V, McArdle, muscle glycogen phosphorylase/GSD type VI, Hers', liver glycogen phosphorylase • GSD type III, Cori's, debranching
lysosomal/LSD: GSD type II, Pompe's, glucosidase
Glucose ⇄ CAC
Glycolysis
MODY 2 • GSD type VII, Tarui's, phosphofructokinase • Triosephosphate isomerase deficiency • Pyruvate kinase deficiency
Pyruvate catabolism PDHA • Fumarase deficiency
Gluconeogenesis
PCD • Fructose bisphosphatase deficiency • GSD type I, von Gierke, glucose 6-phosphatase
Pentose phosphate pathway
Glucose-6-phosphate dehydrogenase deficiency • Pentosuria
Other Hyperoxaluria (Primary hyperoxaluria)
Glycogen storage disease type II (also called Pompe disease or acid maltase deficiency) is an autosomal recessive metabolic disorder[1] which damages muscle and nerve cells throughout the body. It is caused by an accumulation of glycogen in the lysosome due to deficiency of the lysosomal acid alpha-glucosidase enzyme. It is the only glycogen storage disease with a defect in lysosomal metabolism, and the first glycogen storage disease to be identified, in 1932.
The build-up of glycogen causes progressive muscle weakness (myopathy) throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system.
Glycogen storage disease type II
Classification and external resources
ICD-10
E74.0
ICD-9
271.0
OMIM
232300
DiseasesDB
5296
eMedicine
med/908 ped/1866
MeSH
D006009
Variants
Pompe disease has historically been divided into three forms defined by age of onset and progression of symptoms (see below). More recently there has been a trend to divide the disease into two groups: infantile onset (involving the massive enlargement of the heart) and late onset (no heart enlargement).[citation needed]
Infantile, or early onset, is noticed shortly after birth. Symptoms include severe lack of muscle tone, weakness, an enlarged liver (hepatomegaly), and an enlarged heart (cardiomegaly).[citation needed] Mental function is not affected. Development appears normal for the first weeks or months but slowly declines as the disease progresses. Swallowing may become difficult and the tongue may protrude and become enlarged. Most children die from respiratory or cardiac complications before 2 years of age.[citation needed]
Juvenile onset symptoms appear in early to late childhood and include progressive weakness of respiratory muscles in the trunk, diaphragm and lower limbs, as well as exercise intolerance. Intelligence is normal.[citation needed]
Adult onset symptoms also involve generalized muscle weakness and wasting of respiratory muscles in the trunk, lower limbs, and diaphragm. Many patients report respiratory distress, headache at night or upon waking, diminished deep tendon reflexes, and proximal muscle weakness, such as difficulty in climbing stairs. Intellect is not affected. A small number of adult patients live without major symptoms or limitations.[citation needed]
Pompe's disease is one of the infiltrative causes of restrictive cardiomyopathy.[citation needed]
Treatment
Cardiac and respiratory complications are treated symptomatically. Physical and occupational therapy may be beneficial for some patients. Alterations in diet may provide temporary improvement but will not alter the course of the disease.[citation needed] Genetic counseling can provide families with information regarding risk in future pregnancies.
On April 28, 2006 the US Food and Drug Administration approved a biologics license application (BLA) for Myozyme (alglucosidase alfa, rhGAA),[2] the first treatment for patients with Pompe disease. This was based on enzyme replacement therapy work pioneered by Drs Arnold Reuser and Ans van der Ploeg at Erasmus University, Rotterdam.[3] Myozyme falls under the FDA Orphan Drug designation and was approved under a priority review.
The currently approved Myozyme is manufactured by Genzyme Corp. in Cambridge, Massachusetts, USA. Its development was a complex process. Genzyme first partnered with Pharming Group NV who had managed to produce acid alpha-glucosidase from the milk of transgentic rabbits. They also partnered with a second group based at Duke University using Chinese hamster ovary cells. In 2001 it acquired Novazyme which was also working on this enzyme. Genzyme also had its own product (Myozyme) under development. In November 2001 Genzyme chief executive Henri Termeer organised a systematic comparison of the various potential drugs in transgenic mice. It was found that Myozyme was the most efficatious and easiest to manufacture. Work on the other products was then discontinued.
The FDA has approved Myozyme for administration by intravenous infusion of solution into a vein. The safety and efficacy of Myozyme were assessed in two separate clinical trials in 39 infantile-onset patients with Pompe disease ranging in age from 1 month to 3.5 years at the time of the first infusion. Myozyme costs an average of $300,000 a year, and must be taken for the patients' entire life. The treatment is not without side effects which include fever, cardiac failure, pneumonia, respiratory failure and rarely shock. Some insurers have refused to pay for it.[4] The treatment is better at stabilizing the clinical condition than reversing the pathological changes that have already occurred. Early diagnosis leads to better outcomes.
On August 14, 2006, Health Canada approved Myozyme for the treatment of Pompe disease. On June 14, 2007 the Canadian Common Drug Review issued their recommendations regarding public funding for Myozyme therapy. Their recommendation was to provide funding to treat a very small subset of Pompe patients (Infants less one year of age with Cardiomyopathy).[5] The vast majority of developed countries are providing access to therapy for all diagnosed Pompe patients.[6]
In June 2007 it was reported that ZyStor Therapeutics was in the process of developing an enzyme replacement therapy for Pompe disease by leveraging their glycosylation independent lysosomal targeting technology (GILT).[7]
Prognosis
The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. Without treatment the disease is particularly lethal in infants and young children.
Myozyme (alglucosidase alfa), which helps break down glucose, is a combined form of the human enzyme acid alpha-glucosidase, and is also currently being used to replace the missing enzyme. In a study[8] which included the largest cohort of patients with Pompe disease treated with enzyme replacement therapy (ERT) to date findings showed that Myozyme treatment clearly prolongs ventilator-free survival and overall survival in patients with infantile-onset Pompe disease as compared to an untreated historical control population. Furthermore, the study demonstrated that initiation of ERT prior to 6 months of age, which could be facilitated by newborn screening, shows great promise to reduce the mortality and disability associated with this devastating disorder.
On December 13, 2007, Genzyme released the initial results of its Late Onset Treatment Study (LOTS). The study was undertaken to evaluate the safety and efficacy of Myozyme in juvenile and adult patients with Pompe disease. LOTS was a randomized, double-blind, placebo-controlled study that enrolled 90 patients at eight primary sites in the United States and Europe. Participants received either Myozyme or a placebo every other week for 18 months. The average age of study participants was 44 years. The primary efficacy endpoints of the study sought to determine the effect of Myozyme on functional endurance as measured by the six-minute walk test and to determine the effect of Myozyme on pulmonary function as measured by percent predicted forced vital capacity.
The results showed that, at 18 months, patients treated with Myozyme increased their distance walked in six minutes by an average of approximately 30 meters as compared with the placebo group (P=0.0283; Wilcoxon test). The placebo group did not show any improvement from baseline. The average baseline distance walked in six minutes in both groups was approximately 325 meters. Percent predicted forced vital capacity in the group of patients treated with Myozyme increased by 1 percent at 18 months. In contrast, it declined by approximately 3 percent in the placebo group (P=0.0026; Wilcoxon test). The average baseline percent predicted forced vital capacity in both groups was approximately 55 percent.
The results for both efficacy endpoints were consistent across various prospectively defined subgroups.
Epidemiology
Glycogen storage disease type II has an autosomal recessive pattern of inheritance.
The disorder is estimated to occur in about 1 in 40,000 births. Worldwide there are thought to be about 5,000 to 10,000 suffers of this disease.
It has an autosomal recessive inheritance pattern. This means the defective gene is located on an autosome, and two copies of the gene—one from each parent—are required to be born with the disorder. As with all cases of autosomal recessive inheritance, children have a 1 in 4 chance of inheriting the disorder when both parents carry the defective gene, and although both parents carry one copy of the defective gene, they are usually not affected by the disorder.
History
The disease is named after Johann Pompe, who characterized it in 1932.[9][10] Pompe described accumulation of glycogen in muscle tissue in some cases of a previously unknown disorder. This accumulation was difficult to explain as the enzymes involved in the usual metabolism of glucose and glycogen were all present and functioning.
The basis for the disease remained a puzzle until Christian de Duve's discovery of lysosomes in 1955 for which he won the Nobel Prize in 1974. His co-worker Henri G. Hers realised in 1965 that the deficiency of a lysosomal enzyme (alpha glucosidase) for the breakdown of glycogen could explain the symptoms of Pompe disease. This discovery lead to establishing the concept of lysosomal storage diseases of which 49 have been described (to date).
Despite recognizing the basis for the disease treatment proved difficult. Administration of the enzyme lead to its uptake by the liver and not the muscle cells where it is needed. Despite this work at Erasmus MC University Medical Center, Rotterdam began in the '70s. In the early 1990s two Dutch scientists, Arnold Reuser and Ans van der Ploeg a PhD student, had the idea that phosphorylated enzyme would be taken via by the mannose-6-phosphate receptors in lysosomes thus allowing the enzyme to be targeted. Using alpha-glucosidase containing phosphorylated mannose residues they were able to show that an increase in the enzyme's activity in the muscles.[11] The increases reported - 43% increase in skeletal muscle and 70% in the heart - were likely to be clinically significant.
They cloned the acid alpha-glucosidase gene and then made the first mouse model of Pompe's disease. A second model was developed by Yuan-Tsong Chen and colleagues at Duke University using the quail. (Dr. Chen is the director of the Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.) The results of the work at Dukes were impressive with one treated animal recovering to the point of being able to fly again.[12]
This was followed by production of alpha-glucosidase in Chinese hamster ovary (CHO) cells and in the milk of transgenic rabbits.[13] This work eventually culminated in the start of clinical trials with the first clinical trial including 4 babies taking place at Erasmus MC Sophia Children’s Hospital in 1999. This was organised by Pharming in the Netherlands. A second trial in 2001 organised by Dr Chen and Synpac, a Taiwan-based company, used enzyme grown in CHO cells[14] (陳垣崇) while he was at Duke University. Both trials were successful.
Genzyme which had an existing enzyme replacement therapy for Gaucher's disease became involved at this point. They developed a product of their own for Pompe's disease also grown in CHO cells. This is now marketed as Myozyme.
Much of the funding for research in this field was provided by the Association of Glycogen Storage Disorders. This association was founded by a Scotsman - Kevin O’Donnell - whose son Calum aged eight months died from Pompe's disease in 1993. A grant from the AGSD-UK in 1996 funded the work that showed that replacement treatment could work. A second fund-raising group was formed in 1999 - the International Pompe Association.
John Crowley became involved in the fund-raising efforts in 1998 after two of his children were diagnosed with Pompe's. He joined the company Novazyme in 1999 which was working on enzyme replacement treatment for Pompe's. Novazyme was sold to Genzyme in 2001 for over US$100 million.
[hide]
v • d • e
Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders (including glycogen storage diseases) (E73-74, 271)
Sucrose, transport
(extracellular) Disaccharide catabolism Lactose intolerance • Sucrose intolerance
Monosaccharide transport Glucose-galactose malabsorption • Inborn errors of renal tubular transport (Renal glycosuria) • Fructose malabsorption
Hexose → glucose
Monosaccharide catabolism fructose: Essential fructosuria • Fructose intolerance
galactose/galactosemia : GALK deficiency • GALT deficiency/GALE deficiency
Glucose ⇄ glycogen
Glycogenesis
GSD type 0, glycogen synthase • GSD type IV, Andersen's, branching
Glycogenolysis
extralysosomal: GSD type V, McArdle, muscle glycogen phosphorylase/GSD type VI, Hers', liver glycogen phosphorylase • GSD type III, Cori's, debranching
lysosomal/LSD: GSD type II, Pompe's, glucosidase
Glucose ⇄ CAC
Glycolysis
MODY 2 • GSD type VII, Tarui's, phosphofructokinase • Triosephosphate isomerase deficiency • Pyruvate kinase deficiency
Pyruvate catabolism PDHA • Fumarase deficiency
Gluconeogenesis
PCD • Fructose bisphosphatase deficiency • GSD type I, von Gierke, glucose 6-phosphatase
Pentose phosphate pathway
Glucose-6-phosphate dehydrogenase deficiency • Pentosuria
Other Hyperoxaluria (Primary hyperoxaluria)
Procedures
Central Venous Line
A central venous catheter ("central line", "CVC", "central venous line" or "central venous access catheter") is a catheter placed into a large vein in the neck (internal jugular vein), chest (subclavian vein) or groin (femoral vein). It is used to administer medication or fluids, obtain blood tests (specifically the "mixed venous oxygen saturation"), and directly obtain cardiovascular measurements such as the central venous pressure. Certain medications, such as inotropes and amiodarone, are preferably given through a central line.
Types
There are several types of central venous catheters
Tunneled catheter
This type of catheter is inserted into a vein at one location (neck, chest or groin), and tunneled under the skin to a separate exit site, where it emerges from underneath the skin. It is held in place by a Dacron cuff, just underneath the skin at the exit site. The exit site is typically located in the chest, making the access ports less visible than if they were to directly protrude from the neck. Passing the catheter under the skin helps to prevent infection and provides stability.
Implanted port
Implanted port
A port is similar to a tunneled catheter but is left entirely under the skin. Medicines are injected through the skin into the catheter. Some implanted ports contain a small reservoir that can be refilled in the same way. After being filled, the reservoir slowly releases the medicine into the bloodstream. An implanted port is less obvious than a tunneled catheter and requires very little daily care. It has less impact on a person's activities than a PICC line or a tunneled catheter. Surgically implanted infusion port placed below the clavicle (infraclavicular fossa), catheter threaded into the right atrium through large vein. Accessed via non-coring "Huber" needle through the skin. May need to use topical anesthetic prior to accessing port. Used for medications, chemotherapy, TPN, and blood. Easy to maintain for home-based therapy.
PICC line
A peripherally inserted central catheter, or PICC line (pronounced "pick"), is a central venous catheter inserted into a vein in the arm rather than a vein in the neck or chest.
Technical description
Triluminal catheter
Dependent on its use, the catheter is monoluminal, biluminal or triluminal, dependent on the actual number of tubes or lumens (1, 2 and 3 respectively). Some catheters have 4 or 5 lumens, depending on the reason for their use.
The catheter is usually held in place by a suture or staple and an occlusive dressing. Regular flushing with saline or a heparin-containing solution keeps the line patent and prevents thrombosis. Certain lines are impregnated with antibiotics, silver-containing substances (specifically silver sulfadiazine) and/or chlorhexidine to reduce infection risk.
Specific types of long-term central lines are the Hickman catheters, which require clamps to make sure the valve is closed, and Groshong catheters, which have a valve that opens as fluid is withdrawn or infused and remains closed when not in use. Hickman and Groshong lines need more specific measures to prevent infection. Hence, they are inserted into the jugular vein but then tunneled under the skin to maximize the distance a pathogen would need to travel to enter the bloodstream. Hickman lines also have a "cuff" under the skin, again to prevent bacterial migration.[citation needed]
Indications and uses
Indications for the use of central lines include
• Monitoring of the central venous pressure (CVP) in acutely ill patients to quantify fluid balance
• Long-term Intravenous antibiotics
• Long-term Parenteral nutrition especially in chronically ill patients
• Long-term pain medications
• Chemotherapy
• Drugs that are prone to cause phlebitis in peripheral veins (caustic), such as:
o Calcium chloride
o Chemotherapy
o Hypertonic saline
o Potassium chloride
o Amiodarone
• Plasmapheresis
• Dialysis
• Frequent blood draws
• Frequent or persistent requirement for intravenous access
• Need for intravenous therapy when peripheral venous access is impossible
o Blood
o Medication
o Rehydration
Central venous catheters usually remain in place for a longer period of time, especially when the reason for their use is longstanding (such as total parenteral nutrition in a chronically ill patient). For such indications, a Hickman line, a PICC line or a portacath may be considered because of their smaller infection risk. Sterile technique is highly important here, as a line may serve as a porte d'entrée (place of entry) for pathogenic organisms, and the line itself may become infected with organisms such as Staphylococcus aureus and coagulase-negative Staphylococci.[citation needed]
Insertion
Triple lumen in jugular vein
The skin is cleaned, and local anesthetic applied if required. The location of the vein is then identified by landmarks or with the use of a small ultrasound device. A hollow needle is advanced through the skin until blood is aspirated; the color of the blood and the rate of its flow help distinguish it from arterial blood (suggesting that an artery has been accidentally punctured).[citation needed]
The Seldinger technique is then employed to insert the line. This means that a blunt guidewire is passed through the needle, and the needle is then removed. A dilating device may be passed over the guidewire to slightly enlarge the tract, and the central line itself is then passed over the guidewire, which is then removed. All the lumens of the line are aspirated (to ensure that they are all positioned inside the vein) and flushed.[citation needed]
For jugular and subclavian lines, a chest X-ray is typically performed to ensure the line is positioned inside the superior vena cava and, in the case of insertion through the subclavian vein, that there is no resultant pneumothorax.
Complications
Central line insertion may cause a number of complications. The benefit expected from their use therefore needs to outweigh the risk of those complications.
Pneumothorax
Pneumothorax (for central lines placed in the chest); the incidence is thought to be higher with subclavian vein catheterization. In catheterization of the internal jugular vein, the risk of pneumothorax can be minimized by the use of ultrasound guidance. For experienced clinicians, the incidence of pneumothorax is about 1%. Some official bodies, e.g. the National Institute for Health and Clinical Excellence (UK), recommend the routine use of ultrasonography to minimize complications
Infection
All catheters can introduce bacteria into the bloodstream, but CVCs are known for occasionally causing Staphylococcus aureus and Staphylococcus epidermidis sepsis. Infection risks were initially thought to be less in jugular lines, but this only seems to be the case if the patient is obese
If a patient with a central line develops signs of infection, blood cultures are taken from both the catheter and from a vein elsewhere in the body. If the culture from the central line grows bacteria much earlier (>2 hours) than the other site, the line is the likely source of the infection. Quantitative blood culture is even more accurate, but this is not widely available
Generally, antibiotics are used, and occasionally the catheter will have to be removed. In the case of bacteremia from Staphylococcus aureus, removing the catheter without administering antibiotics is not adequate as 38% of such patients may still develop endocarditis.
In a clinical practice guideline, the American Centers for Disease Control and Prevention recommends against routine culturing of central venous lines upon their removal. The guideline makes a number of further recommendations to prevent line infections.
To prevent infection, stringent cleaning of the catheter insertion site is advised. Povidone-iodine solution is often used for such cleaning, but chlorhexidine appears to be twice as good as iodine. Routine replacement of lines makes no difference in preventing infection.
Other complications
Rarely, small amounts of air are sucked into the vein as a result of the negative intrathoracic pressure.[citation needed] If these air bubbles obstruct blood vessels, this is known as an air embolism.
Hemorrhage (bleeding) and formation of a hematoma (bruise) is slightly more common in jugular venous lines than in others.
Arrhythmia may occur during the insertion process when the wire comes in contact with the endocardium. It typically resolved when the wire is pulled back.
Arterial catheter
An arterial line, or art-line, is a thin catheter inserted into an artery. It is most commonly used in intensive care medicine to monitor the blood pressure real-time (rather than by intermittent measurement), and to obtain samples for arterial blood gas measurements. It is not generally used to administer medication.
An arterial line is usually inserted in the wrist (radial artery); but can also be inserted into the elbow (brachial artery), groin (femoral artery), foot (dorsalis pedis artery).
Insertion is often painful; however an anesthetic such as Lidocaine can be used to make the insertion more tolerable, but this can make insertion more difficult.
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Implantable Cardioverter Defibrillator (ICD) Insertion
The heart's electrical conduction system
The heart is, in the simplest terms, a pump made up of muscle tissue. Like all pumps, the heart requires a source of energy in order to function. The heart's pumping energy comes from an indwelling electrical conduction system.
An electrical stimulus is generated by the sinus node (also called the sinoatrial node, or SA node), which is a small mass of specialized tissue located in the right atrium (right upper chamber) of the heart.
The sinus node generates an electrical stimulus regularly at 60 to 100 times per minute under normal conditions. This electrical stimulus travels down through the conduction pathways (similar to the way electricity flows through power lines from the power plant to your house) and causes the heart's chambers to contract and pump out blood.
The right and left atria (the two upper chambers of the heart) are stimulated first and contract a short period of time before the right and left ventricles (the two lower chambers of the heart).
The electrical impulse travels from the sinus node to the atrioventricular (AV) node, where it stops for a very short period, then continues down the conduction pathways via the "bundle of His" into the ventricles. The bundle of His divides into right and left pathways to provide electrical stimulation to both ventricles.
Reasons for the Procedure
A pacemaker may be inserted in order to provide stimulation for a faster heart rate when the heart is beating too slowly, and when other treatment methods, such as medication, have not improved the heart rate.
An ICD may be inserted in order to provide fast pacing (ATP), cardioversion (small shock), or defibrillation (larger shock) when the heart beats too fast.
Problems with the heart rhythm may cause difficulties because the heart is unable to pump an adequate amount of blood to the body. If the heart rate is too slow, the blood is pumped too slowly.
If the heart rate is too fast or too irregular, the heart chambers are unable to fill up with enough blood to pump out with each beat. When the body does not receive enough blood, symptoms such as fatigue, dizziness, fainting, and/or chest pain may occur.
Some examples of rhythm problems for which a pacemaker or ICD might be inserted include:
• atrial fibrillation - occurs when the atria beat irregularly and too fast
• ventricular fibrillation - occurs when the ventricles beat irregularly and too fast
• bradycardia - occurs when the heart beats too slow
• tachycardia - occurs when the heart beats too fast
• heart block - occurs when the electrical signal is delayed after leaving the SA node; there are several types of heart blocks, and each one has a distinctive ECG tracing
There may be other reasons for your physician to recommend a pacemaker or ICD insertion.
Risks of the Procedure
Possible risks of pacemaker or ICD insertion include, but are not limited to, the following:
• bleeding from the incision or catheter insertion site
• damage to the vessel at the catheter insertion site
• infection of the incision or catheter site
• pneumothorax - air becomes trapped in the pleural space causing the lung to collapse
If you are pregnant or suspect that you may be pregnant, you should notify your physician. If you are lactating, or breastfeeding, you should notify your physician.
Patients who are allergic to or sensitive to medications or latex should notify their physician.
For some patients, having to lie still on the procedure table for the length of the procedure may cause some discomfort or pain.
There may be other risks depending upon your specific medical condition. Be sure to discuss any concerns with your physician prior to the procedure.
Before the Procedure
• Your physician will explain the procedure to you and offer you the opportunity to ask any questions that you might have about the procedure.
• You will be asked to sign a consent form that gives your permission to do the test. Read the form carefully and ask questions if something is not clear.
• You will need to fast for a certain period of time prior to the procedure. Your physician will notify you how long to fast, usually overnight.
• If you are pregnant or suspect that you are pregnant, you should notify your physician.
• Notify your physician if you are sensitive to or are allergic to any medications, iodine, latex, tape, or anesthetic agents (local and general).
• Notify your physician of all medications (prescription and over-the-counter) and herbal supplements that you are taking.
• Notify your physician if you have heart valve disease, as you may need to receive an antibiotic prior to the procedure.
• Notify your physician if you have a history of bleeding disorders or if you are taking any anticoagulant (blood-thinning) medications, aspirin, or other medications that affect blood clotting. It may be necessary for you to stop some of these medications prior to the procedure.
• Your physician may request a blood test prior to the procedure to determine how long it takes your blood to clot. Other blood tests may be done as well.
• You may receive a sedative prior to the procedure to help you relax. If a sedative is given, you will need someone to drive you home afterwards.
• The upper chest may be shaved or clipped prior to the procedure.
• Based upon your medical condition, your physician may request other specific preparation.
During the Procedure
Chest X-ray with Implanted Pacemaker
A pacemaker or implanted cardioverter defibrillator may be performed on an outpatient basis or as part of your stay in a hospital. Procedures may vary depending on your condition and your physician's practices.
Generally, a pacemaker or ICD insertion follows this process:
1. You will be asked to remove any jewelry or other objects that may interfere with the procedure.
2. You will be asked to remove your clothing and will be given a gown to wear.
3. You will be asked to empty your bladder prior to the procedure.
4. An intravenous (IV) line will be started in your hand or arm prior to the procedure for injection of medication and to administer IV fluids, if needed.
5. You will be placed in a supine (on your back) position on the procedure table.
6. You will be connected to an electrocardiogram (ECG or EKG) monitor that records the electrical activity of the heart and monitors the heart during the procedure using small, adhesive electrodes. Your vital signs (heart rate, blood pressure, breathing rate, and oxygenation level) will be monitored during the procedure.
7. Large electrode pads will be placed on the front and back of the chest.
8. You will receive a sedative medication in your IV before the procedure to help you relax. However, you will likely remain awake during the procedure.
9. The pacemaker or ICD insertion site will be cleansed with antiseptic soap.
10. Sterile towels and a sheet will be placed around this area.
11. A local anesthetic will be injected into the skin at the insertion site.
12. Once the anesthetic has taken effect, the physician will make a small incision at the insertion site.
13. A sheath, or introducer, is inserted into a blood vessel, usually under the collarbone. The sheath is a plastic tube through which the pacer/ICD lead wire will be inserted into the blood vessel and advanced into the heart.
14. It will be very important for you to remain still during the procedure so that the catheter placement will not be disturbed and to prevent damage to the insertion site.
15. The lead wire will be inserted through the introducer into the blood vessel. The physician will advance the lead wire through the blood vessel into the heart.
16. Once the lead wire is inside the heart, it will be tested to verify proper location and that it works. There may be one, two, or three lead wires inserted, depending on the type of device your physician has chosen for your condition. Fluoroscopy, (a special type of x-ray that will be displayed on a TV monitor), may be used to assist in testing the location of the leads.
17. Once the lead wire has been tested, an incision will be made close to the location of the catheter insertion (just under the collarbone). You will receive local anesthetic medication before the incision is made.
18. The pacemaker/ICD generator will be slipped under the skin through the incision after the lead wire is attached to the generator. Generally, the generator will be placed on the non-dominant side. (If you are right-handed, the device will be placed in your upper left chest. If you are left-handed, the device will be placed in your upper right chest).
19. The ECG will be observed to ensure that the pacer is working correctly.
20. The skin incision will be closed with sutures, adhesive strips, or a special glue.
21. A sterile bandage/dressing will be applied.
After the Procedure
In the hospital
After the procedure, you may be taken to the recovery room for observation or returned to your hospital room. A nurse will monitor your vital signs for a specified period of time.
You should immediately inform your nurse if you feel any chest pain or tightness, or any other pain at the incision site.
After the specified period of bed rest has been completed, you may get out of bed. The nurse will assist you the first time you get up, and will check your blood pressure while you are lying in bed, sitting, and standing. You should move slowly when getting up from the bed to avoid any dizziness from the period of bedrest.
You will be able to eat or drink once you are completely awake.
The insertion site may be sore or painful, but pain medication may be administered if needed.
Your physician will visit with you in your room while you are recovering. The physician will give you specific instructions and answer any questions you may have.
Once your blood pressure, pulse, and breathing are stable and you are alert, you will be taken to your hospital room or discharged home.
If the procedure is performed on an outpatient basis, you may be allowed to leave after you have completed the recovery process. However, if there are concerns or problems with your ECG, you may stay in the hospital for an additional day (or longer) for monitoring of the ECG.
You should arrange to have someone drive you home from the hospital following your procedure.
At home
You should be able to return to your daily routine within a few days. Your physician will tell you if you will need to take more time in returning to your normal activities. In addition, you should not do any lifting or pulling on anything for a few weeks. You may be instructed not to lift your arms above your head for a period of time.
You will most likely be able to resume your usual diet, unless your physician instructs you differently.
It will be important to keep the insertion site clean and dry. Your physician will give you specific bathing instructions.
Your physician will give you specific instructions about driving. If you had an ICD, you will not be able to drive until your physician gives you approval. Your physician will explain these limitations to you, if they are applicable to your situation.
You will be given specific instructions about what to do if your ICD discharges a shock. For example, you may be instructed to dial 911 or go to the nearest emergency room in the event of a shock from the ICD.
Ask your physician when you will be able to return to work. The nature of your occupation, your overall health status, and your progress will determine how soon you may return to work.
Notify your physician to report any of the following:
• fever and/or chills
• increased pain, redness, swelling, or bleeding or other drainage from the insertion site
• chest pain/pressure, nausea and/or vomiting, profuse sweating, dizziness and/or fainting
• palpitations
Your physician may give you additional or alternate instructions after the procedure, depending on your particular situation.
Foley catheter
Foley catheters are flexible (usually latex) tubes that are passed through the urethra during urinary catheterization and into the bladder to drain urine. They are retained by means of a balloon at the tip which is inflated with sterile water. The balloons typically come in two different sizes: 5 cc and 30 cc. They are commonly made in silicone rubber or natural rubber.
The relative size of a Foley catheter is described using French units (F).[1] The most common sizes are 10 F to 28 F. 1 F is equivalent to 0.33 mm = .013" = 1/77" of diameter. Thus the size in French units is roughly equal to the circumference of the catheter in millimetres.
Side view diagram of male urinary tract with Foley catheter in place to drain urine. A balloon near the tip holds the catheter in place.
Foley catheter (F/Ch. 24) positioned in a male; balloon blocked and outlet plug put on.
Foley catheters come in several sub-types. Coudé (French for elbowed) catheters have a 45° bend at the tip to allow easier passage through an enlarged prostate. Council tip catheters have a small hole at the tip which allows them to be passed over a wire. 3-way catheters are used primarily after bladder, prostate cancer or prostate surgery. They have a third arm or bell that allows an irrigant to pass to the tip of the catheter through a small separate channel into the bladder. This serves to wash away blood and small clots through the primary arm that drains into a collection device. This prevents larger clots, which might plug the catheter, from forming. The second, or inflation, arm has a small plastic valve that allows for the introduction or removal of sterile water through a very small channel to inflate or deflate the retaining balloon.
Foley catheters can also be used to "ripen" the cervix, to allow the induction of labour. The catheter is inserted behind the cervical wall and inflated. The remaining length of the catheter is gently pulled and taped to the inside of the woman's leg. The inflated balloon applies pressure to the cervix, like the baby's head would prior to labour, causing it to dilate. Over time the catheter is adjusted and re-taped to maintain pressure on the cervix. When the cervix has dilated sufficiently, the catheter simply drops out.
They were designed by Frederic Foley, a surgeon working in Boston, Massachusetts, in the 1930s, when he was a medical student
His original design was adopted by C. R. Bard, Inc. of Murray Hill, New Jersey, who manufactured the first prototypes and named them in honor of the surgeon.
A major problem with Foley catheters is that they have a tendency to contribute to urinary tract infections (UTI). This occurs because bacteria can travel up the catheters to the bladder where the urine can become infected. To combat this, the industry is moving to antibiotic coated catheters. This has been helpful, but it has not completely solved this major problem. An additional problem is that Foley catheters tend to become coated over time with a biofilm that can keep them from properly draining the bladder. This increases the degree of static urine left in the bladder, which further contributes to the problem of urinary tract infections. When a Foley catheter becomes clogged, it must be flushed or replaced. Thus keeping Foley Catheters from clogging may help reduce UTIs as well.
When Foley catheters are used
Foley catheters are used during the following situations:
• On patients who are anesthesized or sedated for surgery or other medical care
• On comatose patients
• On some incontinent patients
• On patients whose prostate is enlarged to the point that urine flow from the bladder is cut off. The catheter is kept in until the problem is resolved.
• On patients with acute urinary retention.
• On patients who are unable due to paralysis or physical injury to use either standard toilet facilities or urinals.
• Following urethral surgeries
• Following uretectomy
• Sometimes before Furosemide administration
Alternative treatments
• For obstructed prostates due to BPH: The Spanner Prostatic stent
Lumbar puncture
A patient undergoes a lumbar puncture at the hands of a neurologist. The reddish-brown swirls on the patient's back are tincture of iodine (an antiseptic).
In medicine, a lumbar puncture (colloquially known as a spinal tap) is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid (CSF) for biochemical, microbiological, and cytological analysis, or very rarely as a treatment ("therapeutic lumbar puncture") to relieve increased intracranial pressure.
Indications
The most common purpose for a lumbar puncture is to collect cerebrospinal fluid in a case of suspected meningitis, since there is no other reliable tool with which meningitis, a life-threatening but highly treatable condition, can be excluded. Young infants commonly require lumbar puncture as a part of the routine workup for fever without a source, as they have a much higher risk of meningitis than older persons and do not reliably show signs of meningeal irritation (meningismus). In any age group, subarachnoid hemorrhage, hydrocephalus, benign intracranial hypertension and many other diagnoses may be supported or excluded with this test.
Lumbar punctures may also be done to inject medications into the cerebrospinal fluid ("intrathecally"), particularly for spinal anesthesia or chemotherapy.It may also be used to detect the presence of malignant cells in the CSF,as in carcinomatous meningitis or medulloblastoma. Lumbar punctures can be unpleasant for some people, due to increased sensitivity when the needle is inserted to collect the cerebrospinal fluid.
Contraindications
Lumbar puncture should not be performed when idiopathic (unidentified cause) increased intracranial pressure (ICP) is present. The exception is therapeutic use of lumbar puncture to relieve ICP. Ideally, a CT scan should be performed prior to lumbar puncture to rule out space occupying lesions. Ophthalmoscopy for papilledema should also be performed prior to any LP to check for ICP. Also, lumbar puncture should not be attempted when there is coagulopathy, abnormal respiratory pattern,hypertension with bradycardia and deteriorating consciousness or when there are decreased levels of platelets in the blood (less than 50 x 109/L). Lumbar puncture in cases of vertebral deformities (scoliosis or kyphosis) is also contraindicated in hands of an unexperienced physician.[1][2]
Procedure
Spinal needles used in lumbar puncture.
In performing a lumbar puncture, first the patient is usually placed in a left (or right) lateral position with his/her neck bent in full flexion and knees bent in full flexion up to his/her chest, approximating a fetal position as much as possible. It is also possible to have the patient sit on a stool and bend his/her head and shoulders forward. The area around the lower back is prepared using aseptic technique. Once the appropriate location is palpated, local anaesthetic is infiltrated under the skin and then injected along the intended path of the spinal needle. A spinal needle is inserted between the lumbar vertebrae L3/L4 or L4/L5 and pushed in until there is a "give" that indicates the needle is past the dura mater. The needle is again pushed until there is a second 'give' that indicates the needle is now past the arachnoid mater, and in the subarachnoid space. The stylet from the spinal needle is then withdrawn and drops of cerebrospinal fluid are collected. The opening pressure of the cerebrospinal fluid may be taken during this collection by using a simple column manometer. The procedure is ended by withdrawing the needle while placing pressure on the puncture site. In the past, the patient would often be asked to lie on his/her back for at least six hours and be monitored for signs of neurological problems, though there is no scientific evidence that this provides any benefit. The technique described is almost identical to that used in spinal anesthesia, except that spinal anesthesia is more often done with the patient in a sitting position.
The upright seated position is advantageous in that there is less distortion of spinal anatomy which allows for easier withdrawal of fluid. It is preferred by some practitioners when a lumbar puncture is performed on an obese patient where having them lie on their side would cause a scoliosis and unreliable anatomical landmarks. On the other hand, opening pressures are notoriously unreliable when measured on a seated patient and therefore the left or right lateral (lying down) position is preferred if an opening pressure needs to be measured.
Patient anxiety during the procedure can lead to increased CSF pressure, especially if the person holds their breath, tenses their muscles or flexes their knees too tightly against their chest. Diagnostic analysis of changes in fluid pressure during lumbar puncture procedures requires attention both to the patient's condition during the procedure and to their medical history.[
Reinsertion of the stylet may decrease the rate of post lumbar puncture headaches.
Thoracocentesis or Pleural Tap
Thoracentesis (pronounced /ˌθɔrəsɨnˈtiːsɨs/) (also known as thoracocentesis or pleural tap) is an invasive procedure to remove fluid or air from the pleural space for diagnostic or therapeutic purposes. A cannula, or hollow needle, is carefully introduced into the thorax, generally after administration of local anesthesia. The procedure was first described in 1852.
The recommended location varies depending upon the source. It is critical that the patient holds their breath to avoid piercing the lung. Some sources recommend the midaxillary line, in the ninth intercostal space.
Chest X-ray showing a left-sided pleural effusion (right side of image). This can be treated with thoracentesis.
The illustration shows a person having thoracentesis. The person sits upright and leans on a table. Excess fluid from the pleural space is drained into a bag.
Indications
This procedure is indicated when unexplained fluid accumulates in the chest cavity outside the lung. In more than 90% of cases analysis of pleural fluid yields clinically useful information. If a large amount of fluid is present, then this procedure can also be used therapeutically to remove that fluid and improve patient comfort and lung function.
The most common causes of pleural effusions are cancer, congestive heart failure, pneumonia, and recent surgery. In countries where tuberculosis is common, this is also a common cause of pleural effusions.
When cardiopulmonary status is compromised (i.e. when the fluid or air has its repercussions on the function of heart and lungs), due to air (significant pneumothorax), fluid (pleural fluid) or blood (hemothorax) outside the lung, then this procedure is usually replaced with tube thoracostomy, the placement of a large tube in the pleural space.
Contraindications
An uncooperative patient or a coagulation disorder that can not be corrected are absolute contraindications.
Relative contraindications include cases in which the site of insertion has known bullous disease (e.g. emphysema), use of positive end-expiratory pressure (PEEP, see mechanical ventilation) and only one functioning lung (due to diminished reserve). The aspiration should not exceed 1L as there is a risk of development of pulmonary edema.
Complications
Major complications are pneumothorax (3-30%), hemopneumothorax, hemorrhage, hypotension (low blood pressure due to a vasovagal response) and reexpansion pulmonary edema.
Minor complications include a dry tap (no fluid return), subcutaneous hematoma or seroma, anxiety, dyspnea and cough (after removing large volume of fluid).
The use of ultrasound for needle guidance can minimize the complication rate.
Interpretation of pleural fluid analysis
Several diagnostic tools are available to determine the etiology of pleural fluid.
Transudate versus exudate
First the fluid is either transudate or exudate.
A transudate is defined as pleural fluid to serum total protein ratio of less than 0.5, pleural fluid to serum LDH ratio < 0.6, and absolute pleural fluid LDH < 200 IU or < 2/3 of the normal serum.
An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation. It can apply to plants as well as animals. Its composition varies but generally includes water and the dissolved solutes of the main circulatory fluid such as sap or blood. In the case of blood: it will contain some or all plasma proteins, white blood cells, platelets and (in the case of local vascular damage) red blood cells.
Exudate
• hemorrhage
• Infection
• Inflammation
• Malignancy
• Iatrogenic
• Connective tissue disease
• Endocrine disorders
• Lymphatic disorders vs Constrictive pericarditis
Transudate
• Congestive heart failure
• Nephrotic syndrome
• Hypoalbuminemia
• Cirrhosis
• Atelectasis
• trapped lung
• Peritoneal dialysis
• Superior vena cava obstruction
Amylase
A high amylase level (twice the serum level or the absolute value is greater than 160 Somogy units) in the pleural fluid is indicative of either acute or chronic pancreatitis, pancreatic pseudocyst that has dissected or ruptured into the pleural space, cancer or esophageal rupture.
Glucose
This is considered low if pleural fluid value is less than 50% of normal serum value. The differential diagnosis for this is:
• rheumatoid effusion.The levels are characteristically low (<15 mg/dL).
• lupus effusion
• bacterial empyema
• malignancy
• tuberculosis
• esophageal rupture (Boerhaave syndrome)
pH
Normal pleural fluid pH is approximately 7.60. A pleural fluid pH below 7.30 with normal arterial blood pH has the same differential diagnosis as low pleural fluid glucose.
Triglyceride and cholesterol
Chylothorax (fluid from lymph vessels leaking into the pleural cavity) may be identified by determining triglyceride and cholesterol levels, which are relatively high in lymph. A triglyceride level over 110 mg/dl and the presence of chylomicrons indicate a chylous effusion. The appearance is generally milky but can be serous.
The main cause for chylothorax is rupture of the thoracic duct, most frequently as a result of trauma or malignancy (such as lymphoma).
Cell count and differential
The number of white blood cells can give an indication of infection. The specific subtypes can also give clues as to the type on infection. The amount of red blood cells are an obvious sign of bleeding.
Cultures and stains
If the effusion is caused by infection, microbiological culture may yield the infectious organism responsible for the infection, sometimes before other cultures (e.g. blood cultures and sputum cultures) become positive. A Gram stain may give a rough indication of the causative organism. A Ziehl-Neelsen stain may identify tuberculosis or other mycobacterial diseases.
Cytology
Cytology is an important tool in identifying effusions due to malignancy. The most common causes for pleural fluid are lung cancer, metastasis from elsewhere and mesothelioma. The latter often presents with an effusion. Normal cytology results do not reliably rule out malignancy, but make the diagnosis more unlikely.
Abdominal tap
Alternative Names: Peritoneal tap; Paracentesis
An abdominal tap is a procedure used to remove fluid from the abdomen.
How the Test is Performed
This test may be done in an office setting, treatment room, or hospital.
The puncture site will be cleaned and shaved, if necessary. You then receive a local numbing medicine. The tap needle is inserted 1 - 2 inches into the abdomen. Sometimes a small cut is made to help insert the needle. The fluid is pulled out into a syringe.
The needle is removed. A dressing is placed on the puncture site. If a cut was made, one or two stitches may be used to close it.
There are two kinds of abdominal taps:
• Diagnostic tap -- a small amount of fluid is taken and sent to the laboratory for testing
• Large volume tap -- several liters may be removed to relieve abdominal pain and fluid buildup
How to Prepare for the Test
Let your health care provider know if you:
• Have any allergies to medications or numbing medicine
• Are taking any medications (including herbal remedies)
• Have any bleeding problems
• Might be pregnant
Infants and children:
The preparation you can provide for this test depends on your child's age, previous experience, and level of trust. For general information regarding how you can prepare your child, see the following topics:
• Infant test/procedure preparation (birth - 1 year)
• Toddler test/procedure preparation (1 - 3 years)
• Preschooler test/procedure preparation (3 - 6 years)
• School age test/procedure preparation (6 - 12 years)
• Adolescent test/procedure preparation (12 - 18 years)
How the Test Will Feel
You may feel a stinging sensation from the numbing medicine, or pressure as the needle is inserted.
If a large amount of fluid is taken out, you may feel dizzy or light-headed. Tell the health care provider if you feel dizzy.
Why the Test is Performed
Normally, the abdomen contains only a small amount of fluid. In certain conditions, large amounts of fluid can build up in the abdomen.
An abdominal tap may be done to diagnose the cause of fluid buildup. It may also be done to diagnose infected abdominal fluid, or to remove a large amount of fluid to reduce abdominal pain.
Normal Results
Normally, there should be little or no fluid in the abdomen.
What Abnormal Results Mean
An examination of abdominal fluid may show:
• Appendicitis
• Cirrhosis of the liver
• Damaged bowel
• Heart disease
• Infection
• Kidney disease
• Pancreatic disease
• Tumor (cancerous or noncancerous)
Risks
There is a slight chance of the needle puncturing the bowel, bladder, or a blood vessel in the abdomen. If a large quantity of fluid is removed, there is a slight risk of lowered blood pressure and kidney failure. There is also a slight chance of infection.
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Bone marrow examination
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A Wright's stained bone marrow aspirate smear from a patient with leukemia.
Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called a trephine biopsy) and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, anemia, and pancytopenia. The bone marrow produces the cellular elements of the blood, including platelets, red blood cells and white blood cells. While much information can be gleaned by testing the blood itself (drawn from a vein by phlebotomy), it is sometimes necessary to examine the source of the blood cells in the bone marrow to obtain more information on hematopoiesis; this is the role of bone marrow aspiration and biopsy.
Components of the procedure
A bone marrow harvest.
A volunteer donating bone marrow for scientific research.
Bone marrow samples can be obtained by aspiration and trephine biopsy. Sometimes, a bone marrow examination will include both an aspirate and a biopsy. The aspirate yields semi-liquid bone marrow, which can be examined by a pathologist under a light microscope as well as analyzed by flow cytometry, chromosome analysis, or polymerase chain reaction (PCR). Frequently, a trephine biopsy is also obtained, which yields a narrow, cylindrically shaped solid piece of bone marrow, 2mm wide and 2 cm long (60 μL), which is examined microscopically (sometimes with the aid of immunohistochemistry) for cellularity and infiltrative processes. An aspiration, using a 20 mL syringe, yields approximately 300 μL of bone marrow.[1] A volume greater than 300 μL is not recommended, since it may dilute the sample with peripheral blood.[1]
Comparison
Aspiration Biopsy
Advantages • Fast
• Gives relative quantity of different cell types
• Gives material to further study, e.g. molecular genetics and flow cytometry
• Gives cell and stroma constitution
• Represents all cells
• Explains cause of "dry tap" (aspiration gives no blood cells)
Drawbacks Doesn't represent all cells Slow processing
Aspiration doesn't always represent all cells since, as some such as lymphoma stick to the trabecula, and would thus be missed by a simple aspiration.
Site of procedure
Bone marrow aspiration and trephine biopsy are usually performed on the back of the hipbone, or posterior iliac crest. However, an aspirate can also be obtained from the sternum (breastbone). A trephine biopsy should never be performed on the sternum, due to the risk of injury to blood vessels, lungs or the heart.
How the test is performed
A needle used for bone marrow aspiration, with removable stylet.
A bone marrow biopsy may be done in a health care provider's office or in a hospital. Informed consent for the procedure is typically required. The patient is asked to lie on his or her abdomen (prone position) or on his/her side (lateral decubitus position). The skin is cleansed, and a local anesthetic such as lidocaine is injected to numb the area. Patients may also be pretreated with analgesics and/or anti-anxiety medications, although this is not a routine practice.
Typically, the aspirate is performed first. An aspirate needle is inserted through the skin until it abuts the bone. Then, with a twisting motion, the needle is advanced through the bony cortex (the hard outer layer of the bone) and into the marrow cavity. Once the needle is in the marrow cavity, a syringe is attached and used to aspirate ("suck out") liquid bone marrow. A twisting motion is performed during the aspiration to avoid excess content of blood in the sample, which might be the case if an excessively large sample from one single point is taken.
Subsequently, the biopsy is performed if indicated. A different, larger trephine needle is inserted and anchored in the bony cortex. The needle is then advanced with a twisting motion and rotated to obtain a solid piece of bone marrow. This piece is then removed along with the needle. The entire procedure, once preparation is complete, typically takes 10–15 minutes.
If several samples are taken, the needle is removed between the samples to avoid blood coagulation.
After the procedure
After the procedure is complete, the patient is typically asked to lie flat for 5–10 minutes to provide pressure over the procedure site. After that, assuming no bleeding is observed, the patient can get up and go about their normal activities. Paracetamol (acetaminophen) or other simple analgesics can be used to ease soreness, which is common for 2–3 days after the procedure. Any worsening pain, redness, fever, bleeding or swelling may suggest a complication. Patients are also advised to avoid washing the procedure site for at least 24 hours after the procedure is completed.
Contraindications
There are few contraindications to bone marrow examination. The only absolute reason to avoid performing a bone marrow examination is the presence of a severe bleeding disorder which may lead to serious bleeding after the procedure. If there is a skin or soft tissue infection over the hip, a different site should be chosen for bone marrow examination. Bone marrow aspiration and biopsy can be safely performed even in the setting of extreme thrombocytopenia (low platelet count).
Complications
While mild soreness lasting 12–24 hours is common after a bone marrow examination, serious complications are extremely rare. In a large review, an estimated 55,000 bone marrow examinations were performed, with 26 serious adverse events (0.05%), including one fatality. The same author collected data on over 19,000 bone marrow examinations performed in the United Kingdom in 2003, and found 16 adverse events (0.08% of total procedures), the most common of which was bleeding. In this report, complications, while rare, were serious in individual cases.
Tracheotomy
Completed tracheotomy:
1 - Vocal cords
2 - Thyroid cartilage
3 - Cricoid cartilage
4 - Tracheal cartilages
5 - Balloon cuff
Tracheotomy and tracheostomy are surgical procedures on the neck to open a direct airway through an incision in the trachea (the windpipe). They are performed by emergency physicians, and surgeons. Both surgical and percutaneous techniques are now widely used.
While tracheostomy may have possibly been portrayed on ancient Egyptian tablets,[1] the first correct description of the tracheotomy operation for patients who are suffocating was described by Ibn Zuhr in the 12th century,[2] and the currently used surgical tracheostomy technique was described in 1909 by Dr. Chevalier Jackson of Pittsburgh, Pennsylvania.
Terminology
Tracheotomy, from the Greek root tom- meaning "to cut," refers to the procedure of cutting into the trachea and is an emergency procedure.[3]
A tracheostomy, from the root stom- meaning "mouth," refers to the making of a semi-permanent or permanent opening, and to the opening itself.
Some sources offer different definitions of the above terms. Part of the ambiguity is due to the uncertainty of the intended permanence of the stoma at the time it is created.[4]
Uses of tracheotomy
The conditions in which a tracheotomy may be used are:
• Acute setting - maxillofacial injuries, large tumors of the head and neck, congenital tumors, e.g. branchial cyst, acute inflammation of head and neck, and
• Chronic / elective setting - when there is need for long term mechanical ventilation and tracheal toilet, e.g. comatose patients, surgery to the head and neck.
In emergency settings, in the context of failed endotracheal intubation or where intubation is contraindicated, cricothyroidotomy or mini-tracheostomy may be performed in preference to a tracheostomy.
Tracheotomy procedure
1. Curvilinear skin incision along relaxed skin tension lines (RSTL) between sternal notch and cricoid cartilage.
2. Midline vertical incision dividing strap muscles.
3. Division of thyroid isthmus between ligatures.
4. Elevation of cricoid with cricoid hook.
5. Placement of tracheal incision. An inferior based flap, or Björk flap, (through second and third tracheal rings) is commonly used. The flap is then sutured to the inferior skin margin. Alternatives include a vertical tracheal incision (pediatric) or excision of an ellipse of anterior tracheal wall.
6. Insert tracheostomy tube (with concomitant withdrawal of endotracheal tube), inflate cuff, secure with tape around neck or stay sutures.
7. Connect ventilator tubing.
It is also possible to make a simple vertical incision between tracheal rings (typically 2nd and 3rd) for the incision. Rear end flaps may produce more intratracheal granulation tissue at the site of the incisions, making it less favorable to some surgeons.
Percutaneous tracheotomy procedure
1. Curvilinear skin incision along relaxed skin tension lines between sternal notch and cricoid cartilage.
2. Midline blunt dissection down to the trachea (optional depending on technique).
3. Insertion of 14-gauge plastic cannula and needle with fluid filled syringe attached into trachea. Aspiration of air confirms correct placement of the tip in the trachea.
4. Removal of needle leaving cannula in place.
5. Insertion of soft tipped guide wire into trachea through cannula.
6. Removal of cannula leaving guide wire in place.
7. Tracheal dilatation is now undertaken - different techniques do this in different ways.
1. Ciaglia - the sequential insertion and removal of a series (usually 4-5) of increasing larger dilators over the wire into the trachea.
2. Griggs - insertion of a specially designed pair of guide-wire forceps along the wire into the trachea and then are opened to complete the dilation in one step.
3. Rhino - insertion of a single large tapered dilator over a plastic guidewire reinforcement.
4. Frova Percutwist - insertion of a specially designed screw of increasing diameter which rotates to create the dilatation.
8. Insert tracheostomy tube (with concomitant withdrawal of endotracheal tube), inflate cuff, secure with tape around neck or stay sutures.
9. Connect ventilator tubing.
Risks
During the procedure, there is a risk of damaging the recurrent laryngeal nerves. These nerves control the vocal cords. If one of the nerves is damaged a patient will probably have a problem with his/her voice; if both of the nerves are damaged, the patient will lose his/her speech. This risk of nerve damage is the reason emergency tracheotomies are performed higher up, in the larynx and why tracheotomies have to be done in hospital under anesthetic. Professor Stephen Hawking lost his speech due to a tracheotomy after contracting pneumonia.
Moreover, if the recurrent laryngeal nerve is damaged, the patient will have trouble controlling the flow of air through the rima glottidis, thus ultimately leading to inhibited breathing or suffocation.
A central venous catheter ("central line", "CVC", "central venous line" or "central venous access catheter") is a catheter placed into a large vein in the neck (internal jugular vein), chest (subclavian vein) or groin (femoral vein). It is used to administer medication or fluids, obtain blood tests (specifically the "mixed venous oxygen saturation"), and directly obtain cardiovascular measurements such as the central venous pressure. Certain medications, such as inotropes and amiodarone, are preferably given through a central line.
Types
There are several types of central venous catheters
Tunneled catheter
This type of catheter is inserted into a vein at one location (neck, chest or groin), and tunneled under the skin to a separate exit site, where it emerges from underneath the skin. It is held in place by a Dacron cuff, just underneath the skin at the exit site. The exit site is typically located in the chest, making the access ports less visible than if they were to directly protrude from the neck. Passing the catheter under the skin helps to prevent infection and provides stability.
Implanted port
Implanted port
A port is similar to a tunneled catheter but is left entirely under the skin. Medicines are injected through the skin into the catheter. Some implanted ports contain a small reservoir that can be refilled in the same way. After being filled, the reservoir slowly releases the medicine into the bloodstream. An implanted port is less obvious than a tunneled catheter and requires very little daily care. It has less impact on a person's activities than a PICC line or a tunneled catheter. Surgically implanted infusion port placed below the clavicle (infraclavicular fossa), catheter threaded into the right atrium through large vein. Accessed via non-coring "Huber" needle through the skin. May need to use topical anesthetic prior to accessing port. Used for medications, chemotherapy, TPN, and blood. Easy to maintain for home-based therapy.
PICC line
A peripherally inserted central catheter, or PICC line (pronounced "pick"), is a central venous catheter inserted into a vein in the arm rather than a vein in the neck or chest.
Technical description
Triluminal catheter
Dependent on its use, the catheter is monoluminal, biluminal or triluminal, dependent on the actual number of tubes or lumens (1, 2 and 3 respectively). Some catheters have 4 or 5 lumens, depending on the reason for their use.
The catheter is usually held in place by a suture or staple and an occlusive dressing. Regular flushing with saline or a heparin-containing solution keeps the line patent and prevents thrombosis. Certain lines are impregnated with antibiotics, silver-containing substances (specifically silver sulfadiazine) and/or chlorhexidine to reduce infection risk.
Specific types of long-term central lines are the Hickman catheters, which require clamps to make sure the valve is closed, and Groshong catheters, which have a valve that opens as fluid is withdrawn or infused and remains closed when not in use. Hickman and Groshong lines need more specific measures to prevent infection. Hence, they are inserted into the jugular vein but then tunneled under the skin to maximize the distance a pathogen would need to travel to enter the bloodstream. Hickman lines also have a "cuff" under the skin, again to prevent bacterial migration.[citation needed]
Indications and uses
Indications for the use of central lines include
• Monitoring of the central venous pressure (CVP) in acutely ill patients to quantify fluid balance
• Long-term Intravenous antibiotics
• Long-term Parenteral nutrition especially in chronically ill patients
• Long-term pain medications
• Chemotherapy
• Drugs that are prone to cause phlebitis in peripheral veins (caustic), such as:
o Calcium chloride
o Chemotherapy
o Hypertonic saline
o Potassium chloride
o Amiodarone
• Plasmapheresis
• Dialysis
• Frequent blood draws
• Frequent or persistent requirement for intravenous access
• Need for intravenous therapy when peripheral venous access is impossible
o Blood
o Medication
o Rehydration
Central venous catheters usually remain in place for a longer period of time, especially when the reason for their use is longstanding (such as total parenteral nutrition in a chronically ill patient). For such indications, a Hickman line, a PICC line or a portacath may be considered because of their smaller infection risk. Sterile technique is highly important here, as a line may serve as a porte d'entrée (place of entry) for pathogenic organisms, and the line itself may become infected with organisms such as Staphylococcus aureus and coagulase-negative Staphylococci.[citation needed]
Insertion
Triple lumen in jugular vein
The skin is cleaned, and local anesthetic applied if required. The location of the vein is then identified by landmarks or with the use of a small ultrasound device. A hollow needle is advanced through the skin until blood is aspirated; the color of the blood and the rate of its flow help distinguish it from arterial blood (suggesting that an artery has been accidentally punctured).[citation needed]
The Seldinger technique is then employed to insert the line. This means that a blunt guidewire is passed through the needle, and the needle is then removed. A dilating device may be passed over the guidewire to slightly enlarge the tract, and the central line itself is then passed over the guidewire, which is then removed. All the lumens of the line are aspirated (to ensure that they are all positioned inside the vein) and flushed.[citation needed]
For jugular and subclavian lines, a chest X-ray is typically performed to ensure the line is positioned inside the superior vena cava and, in the case of insertion through the subclavian vein, that there is no resultant pneumothorax.
Complications
Central line insertion may cause a number of complications. The benefit expected from their use therefore needs to outweigh the risk of those complications.
Pneumothorax
Pneumothorax (for central lines placed in the chest); the incidence is thought to be higher with subclavian vein catheterization. In catheterization of the internal jugular vein, the risk of pneumothorax can be minimized by the use of ultrasound guidance. For experienced clinicians, the incidence of pneumothorax is about 1%. Some official bodies, e.g. the National Institute for Health and Clinical Excellence (UK), recommend the routine use of ultrasonography to minimize complications
Infection
All catheters can introduce bacteria into the bloodstream, but CVCs are known for occasionally causing Staphylococcus aureus and Staphylococcus epidermidis sepsis. Infection risks were initially thought to be less in jugular lines, but this only seems to be the case if the patient is obese
If a patient with a central line develops signs of infection, blood cultures are taken from both the catheter and from a vein elsewhere in the body. If the culture from the central line grows bacteria much earlier (>2 hours) than the other site, the line is the likely source of the infection. Quantitative blood culture is even more accurate, but this is not widely available
Generally, antibiotics are used, and occasionally the catheter will have to be removed. In the case of bacteremia from Staphylococcus aureus, removing the catheter without administering antibiotics is not adequate as 38% of such patients may still develop endocarditis.
In a clinical practice guideline, the American Centers for Disease Control and Prevention recommends against routine culturing of central venous lines upon their removal. The guideline makes a number of further recommendations to prevent line infections.
To prevent infection, stringent cleaning of the catheter insertion site is advised. Povidone-iodine solution is often used for such cleaning, but chlorhexidine appears to be twice as good as iodine. Routine replacement of lines makes no difference in preventing infection.
Other complications
Rarely, small amounts of air are sucked into the vein as a result of the negative intrathoracic pressure.[citation needed] If these air bubbles obstruct blood vessels, this is known as an air embolism.
Hemorrhage (bleeding) and formation of a hematoma (bruise) is slightly more common in jugular venous lines than in others.
Arrhythmia may occur during the insertion process when the wire comes in contact with the endocardium. It typically resolved when the wire is pulled back.
Arterial catheter
An arterial line, or art-line, is a thin catheter inserted into an artery. It is most commonly used in intensive care medicine to monitor the blood pressure real-time (rather than by intermittent measurement), and to obtain samples for arterial blood gas measurements. It is not generally used to administer medication.
An arterial line is usually inserted in the wrist (radial artery); but can also be inserted into the elbow (brachial artery), groin (femoral artery), foot (dorsalis pedis artery).
Insertion is often painful; however an anesthetic such as Lidocaine can be used to make the insertion more tolerable, but this can make insertion more difficult.
______________________________________________________________________________
Implantable Cardioverter Defibrillator (ICD) Insertion
The heart's electrical conduction system
The heart is, in the simplest terms, a pump made up of muscle tissue. Like all pumps, the heart requires a source of energy in order to function. The heart's pumping energy comes from an indwelling electrical conduction system.
An electrical stimulus is generated by the sinus node (also called the sinoatrial node, or SA node), which is a small mass of specialized tissue located in the right atrium (right upper chamber) of the heart.
The sinus node generates an electrical stimulus regularly at 60 to 100 times per minute under normal conditions. This electrical stimulus travels down through the conduction pathways (similar to the way electricity flows through power lines from the power plant to your house) and causes the heart's chambers to contract and pump out blood.
The right and left atria (the two upper chambers of the heart) are stimulated first and contract a short period of time before the right and left ventricles (the two lower chambers of the heart).
The electrical impulse travels from the sinus node to the atrioventricular (AV) node, where it stops for a very short period, then continues down the conduction pathways via the "bundle of His" into the ventricles. The bundle of His divides into right and left pathways to provide electrical stimulation to both ventricles.
Reasons for the Procedure
A pacemaker may be inserted in order to provide stimulation for a faster heart rate when the heart is beating too slowly, and when other treatment methods, such as medication, have not improved the heart rate.
An ICD may be inserted in order to provide fast pacing (ATP), cardioversion (small shock), or defibrillation (larger shock) when the heart beats too fast.
Problems with the heart rhythm may cause difficulties because the heart is unable to pump an adequate amount of blood to the body. If the heart rate is too slow, the blood is pumped too slowly.
If the heart rate is too fast or too irregular, the heart chambers are unable to fill up with enough blood to pump out with each beat. When the body does not receive enough blood, symptoms such as fatigue, dizziness, fainting, and/or chest pain may occur.
Some examples of rhythm problems for which a pacemaker or ICD might be inserted include:
• atrial fibrillation - occurs when the atria beat irregularly and too fast
• ventricular fibrillation - occurs when the ventricles beat irregularly and too fast
• bradycardia - occurs when the heart beats too slow
• tachycardia - occurs when the heart beats too fast
• heart block - occurs when the electrical signal is delayed after leaving the SA node; there are several types of heart blocks, and each one has a distinctive ECG tracing
There may be other reasons for your physician to recommend a pacemaker or ICD insertion.
Risks of the Procedure
Possible risks of pacemaker or ICD insertion include, but are not limited to, the following:
• bleeding from the incision or catheter insertion site
• damage to the vessel at the catheter insertion site
• infection of the incision or catheter site
• pneumothorax - air becomes trapped in the pleural space causing the lung to collapse
If you are pregnant or suspect that you may be pregnant, you should notify your physician. If you are lactating, or breastfeeding, you should notify your physician.
Patients who are allergic to or sensitive to medications or latex should notify their physician.
For some patients, having to lie still on the procedure table for the length of the procedure may cause some discomfort or pain.
There may be other risks depending upon your specific medical condition. Be sure to discuss any concerns with your physician prior to the procedure.
Before the Procedure
• Your physician will explain the procedure to you and offer you the opportunity to ask any questions that you might have about the procedure.
• You will be asked to sign a consent form that gives your permission to do the test. Read the form carefully and ask questions if something is not clear.
• You will need to fast for a certain period of time prior to the procedure. Your physician will notify you how long to fast, usually overnight.
• If you are pregnant or suspect that you are pregnant, you should notify your physician.
• Notify your physician if you are sensitive to or are allergic to any medications, iodine, latex, tape, or anesthetic agents (local and general).
• Notify your physician of all medications (prescription and over-the-counter) and herbal supplements that you are taking.
• Notify your physician if you have heart valve disease, as you may need to receive an antibiotic prior to the procedure.
• Notify your physician if you have a history of bleeding disorders or if you are taking any anticoagulant (blood-thinning) medications, aspirin, or other medications that affect blood clotting. It may be necessary for you to stop some of these medications prior to the procedure.
• Your physician may request a blood test prior to the procedure to determine how long it takes your blood to clot. Other blood tests may be done as well.
• You may receive a sedative prior to the procedure to help you relax. If a sedative is given, you will need someone to drive you home afterwards.
• The upper chest may be shaved or clipped prior to the procedure.
• Based upon your medical condition, your physician may request other specific preparation.
During the Procedure
Chest X-ray with Implanted Pacemaker
A pacemaker or implanted cardioverter defibrillator may be performed on an outpatient basis or as part of your stay in a hospital. Procedures may vary depending on your condition and your physician's practices.
Generally, a pacemaker or ICD insertion follows this process:
1. You will be asked to remove any jewelry or other objects that may interfere with the procedure.
2. You will be asked to remove your clothing and will be given a gown to wear.
3. You will be asked to empty your bladder prior to the procedure.
4. An intravenous (IV) line will be started in your hand or arm prior to the procedure for injection of medication and to administer IV fluids, if needed.
5. You will be placed in a supine (on your back) position on the procedure table.
6. You will be connected to an electrocardiogram (ECG or EKG) monitor that records the electrical activity of the heart and monitors the heart during the procedure using small, adhesive electrodes. Your vital signs (heart rate, blood pressure, breathing rate, and oxygenation level) will be monitored during the procedure.
7. Large electrode pads will be placed on the front and back of the chest.
8. You will receive a sedative medication in your IV before the procedure to help you relax. However, you will likely remain awake during the procedure.
9. The pacemaker or ICD insertion site will be cleansed with antiseptic soap.
10. Sterile towels and a sheet will be placed around this area.
11. A local anesthetic will be injected into the skin at the insertion site.
12. Once the anesthetic has taken effect, the physician will make a small incision at the insertion site.
13. A sheath, or introducer, is inserted into a blood vessel, usually under the collarbone. The sheath is a plastic tube through which the pacer/ICD lead wire will be inserted into the blood vessel and advanced into the heart.
14. It will be very important for you to remain still during the procedure so that the catheter placement will not be disturbed and to prevent damage to the insertion site.
15. The lead wire will be inserted through the introducer into the blood vessel. The physician will advance the lead wire through the blood vessel into the heart.
16. Once the lead wire is inside the heart, it will be tested to verify proper location and that it works. There may be one, two, or three lead wires inserted, depending on the type of device your physician has chosen for your condition. Fluoroscopy, (a special type of x-ray that will be displayed on a TV monitor), may be used to assist in testing the location of the leads.
17. Once the lead wire has been tested, an incision will be made close to the location of the catheter insertion (just under the collarbone). You will receive local anesthetic medication before the incision is made.
18. The pacemaker/ICD generator will be slipped under the skin through the incision after the lead wire is attached to the generator. Generally, the generator will be placed on the non-dominant side. (If you are right-handed, the device will be placed in your upper left chest. If you are left-handed, the device will be placed in your upper right chest).
19. The ECG will be observed to ensure that the pacer is working correctly.
20. The skin incision will be closed with sutures, adhesive strips, or a special glue.
21. A sterile bandage/dressing will be applied.
After the Procedure
In the hospital
After the procedure, you may be taken to the recovery room for observation or returned to your hospital room. A nurse will monitor your vital signs for a specified period of time.
You should immediately inform your nurse if you feel any chest pain or tightness, or any other pain at the incision site.
After the specified period of bed rest has been completed, you may get out of bed. The nurse will assist you the first time you get up, and will check your blood pressure while you are lying in bed, sitting, and standing. You should move slowly when getting up from the bed to avoid any dizziness from the period of bedrest.
You will be able to eat or drink once you are completely awake.
The insertion site may be sore or painful, but pain medication may be administered if needed.
Your physician will visit with you in your room while you are recovering. The physician will give you specific instructions and answer any questions you may have.
Once your blood pressure, pulse, and breathing are stable and you are alert, you will be taken to your hospital room or discharged home.
If the procedure is performed on an outpatient basis, you may be allowed to leave after you have completed the recovery process. However, if there are concerns or problems with your ECG, you may stay in the hospital for an additional day (or longer) for monitoring of the ECG.
You should arrange to have someone drive you home from the hospital following your procedure.
At home
You should be able to return to your daily routine within a few days. Your physician will tell you if you will need to take more time in returning to your normal activities. In addition, you should not do any lifting or pulling on anything for a few weeks. You may be instructed not to lift your arms above your head for a period of time.
You will most likely be able to resume your usual diet, unless your physician instructs you differently.
It will be important to keep the insertion site clean and dry. Your physician will give you specific bathing instructions.
Your physician will give you specific instructions about driving. If you had an ICD, you will not be able to drive until your physician gives you approval. Your physician will explain these limitations to you, if they are applicable to your situation.
You will be given specific instructions about what to do if your ICD discharges a shock. For example, you may be instructed to dial 911 or go to the nearest emergency room in the event of a shock from the ICD.
Ask your physician when you will be able to return to work. The nature of your occupation, your overall health status, and your progress will determine how soon you may return to work.
Notify your physician to report any of the following:
• fever and/or chills
• increased pain, redness, swelling, or bleeding or other drainage from the insertion site
• chest pain/pressure, nausea and/or vomiting, profuse sweating, dizziness and/or fainting
• palpitations
Your physician may give you additional or alternate instructions after the procedure, depending on your particular situation.
Foley catheter
Foley catheters are flexible (usually latex) tubes that are passed through the urethra during urinary catheterization and into the bladder to drain urine. They are retained by means of a balloon at the tip which is inflated with sterile water. The balloons typically come in two different sizes: 5 cc and 30 cc. They are commonly made in silicone rubber or natural rubber.
The relative size of a Foley catheter is described using French units (F).[1] The most common sizes are 10 F to 28 F. 1 F is equivalent to 0.33 mm = .013" = 1/77" of diameter. Thus the size in French units is roughly equal to the circumference of the catheter in millimetres.
Side view diagram of male urinary tract with Foley catheter in place to drain urine. A balloon near the tip holds the catheter in place.
Foley catheter (F/Ch. 24) positioned in a male; balloon blocked and outlet plug put on.
Foley catheters come in several sub-types. Coudé (French for elbowed) catheters have a 45° bend at the tip to allow easier passage through an enlarged prostate. Council tip catheters have a small hole at the tip which allows them to be passed over a wire. 3-way catheters are used primarily after bladder, prostate cancer or prostate surgery. They have a third arm or bell that allows an irrigant to pass to the tip of the catheter through a small separate channel into the bladder. This serves to wash away blood and small clots through the primary arm that drains into a collection device. This prevents larger clots, which might plug the catheter, from forming. The second, or inflation, arm has a small plastic valve that allows for the introduction or removal of sterile water through a very small channel to inflate or deflate the retaining balloon.
Foley catheters can also be used to "ripen" the cervix, to allow the induction of labour. The catheter is inserted behind the cervical wall and inflated. The remaining length of the catheter is gently pulled and taped to the inside of the woman's leg. The inflated balloon applies pressure to the cervix, like the baby's head would prior to labour, causing it to dilate. Over time the catheter is adjusted and re-taped to maintain pressure on the cervix. When the cervix has dilated sufficiently, the catheter simply drops out.
They were designed by Frederic Foley, a surgeon working in Boston, Massachusetts, in the 1930s, when he was a medical student
His original design was adopted by C. R. Bard, Inc. of Murray Hill, New Jersey, who manufactured the first prototypes and named them in honor of the surgeon.
A major problem with Foley catheters is that they have a tendency to contribute to urinary tract infections (UTI). This occurs because bacteria can travel up the catheters to the bladder where the urine can become infected. To combat this, the industry is moving to antibiotic coated catheters. This has been helpful, but it has not completely solved this major problem. An additional problem is that Foley catheters tend to become coated over time with a biofilm that can keep them from properly draining the bladder. This increases the degree of static urine left in the bladder, which further contributes to the problem of urinary tract infections. When a Foley catheter becomes clogged, it must be flushed or replaced. Thus keeping Foley Catheters from clogging may help reduce UTIs as well.
When Foley catheters are used
Foley catheters are used during the following situations:
• On patients who are anesthesized or sedated for surgery or other medical care
• On comatose patients
• On some incontinent patients
• On patients whose prostate is enlarged to the point that urine flow from the bladder is cut off. The catheter is kept in until the problem is resolved.
• On patients with acute urinary retention.
• On patients who are unable due to paralysis or physical injury to use either standard toilet facilities or urinals.
• Following urethral surgeries
• Following uretectomy
• Sometimes before Furosemide administration
Alternative treatments
• For obstructed prostates due to BPH: The Spanner Prostatic stent
Lumbar puncture
A patient undergoes a lumbar puncture at the hands of a neurologist. The reddish-brown swirls on the patient's back are tincture of iodine (an antiseptic).
In medicine, a lumbar puncture (colloquially known as a spinal tap) is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid (CSF) for biochemical, microbiological, and cytological analysis, or very rarely as a treatment ("therapeutic lumbar puncture") to relieve increased intracranial pressure.
Indications
The most common purpose for a lumbar puncture is to collect cerebrospinal fluid in a case of suspected meningitis, since there is no other reliable tool with which meningitis, a life-threatening but highly treatable condition, can be excluded. Young infants commonly require lumbar puncture as a part of the routine workup for fever without a source, as they have a much higher risk of meningitis than older persons and do not reliably show signs of meningeal irritation (meningismus). In any age group, subarachnoid hemorrhage, hydrocephalus, benign intracranial hypertension and many other diagnoses may be supported or excluded with this test.
Lumbar punctures may also be done to inject medications into the cerebrospinal fluid ("intrathecally"), particularly for spinal anesthesia or chemotherapy.It may also be used to detect the presence of malignant cells in the CSF,as in carcinomatous meningitis or medulloblastoma. Lumbar punctures can be unpleasant for some people, due to increased sensitivity when the needle is inserted to collect the cerebrospinal fluid.
Contraindications
Lumbar puncture should not be performed when idiopathic (unidentified cause) increased intracranial pressure (ICP) is present. The exception is therapeutic use of lumbar puncture to relieve ICP. Ideally, a CT scan should be performed prior to lumbar puncture to rule out space occupying lesions. Ophthalmoscopy for papilledema should also be performed prior to any LP to check for ICP. Also, lumbar puncture should not be attempted when there is coagulopathy, abnormal respiratory pattern,hypertension with bradycardia and deteriorating consciousness or when there are decreased levels of platelets in the blood (less than 50 x 109/L). Lumbar puncture in cases of vertebral deformities (scoliosis or kyphosis) is also contraindicated in hands of an unexperienced physician.[1][2]
Procedure
Spinal needles used in lumbar puncture.
In performing a lumbar puncture, first the patient is usually placed in a left (or right) lateral position with his/her neck bent in full flexion and knees bent in full flexion up to his/her chest, approximating a fetal position as much as possible. It is also possible to have the patient sit on a stool and bend his/her head and shoulders forward. The area around the lower back is prepared using aseptic technique. Once the appropriate location is palpated, local anaesthetic is infiltrated under the skin and then injected along the intended path of the spinal needle. A spinal needle is inserted between the lumbar vertebrae L3/L4 or L4/L5 and pushed in until there is a "give" that indicates the needle is past the dura mater. The needle is again pushed until there is a second 'give' that indicates the needle is now past the arachnoid mater, and in the subarachnoid space. The stylet from the spinal needle is then withdrawn and drops of cerebrospinal fluid are collected. The opening pressure of the cerebrospinal fluid may be taken during this collection by using a simple column manometer. The procedure is ended by withdrawing the needle while placing pressure on the puncture site. In the past, the patient would often be asked to lie on his/her back for at least six hours and be monitored for signs of neurological problems, though there is no scientific evidence that this provides any benefit. The technique described is almost identical to that used in spinal anesthesia, except that spinal anesthesia is more often done with the patient in a sitting position.
The upright seated position is advantageous in that there is less distortion of spinal anatomy which allows for easier withdrawal of fluid. It is preferred by some practitioners when a lumbar puncture is performed on an obese patient where having them lie on their side would cause a scoliosis and unreliable anatomical landmarks. On the other hand, opening pressures are notoriously unreliable when measured on a seated patient and therefore the left or right lateral (lying down) position is preferred if an opening pressure needs to be measured.
Patient anxiety during the procedure can lead to increased CSF pressure, especially if the person holds their breath, tenses their muscles or flexes their knees too tightly against their chest. Diagnostic analysis of changes in fluid pressure during lumbar puncture procedures requires attention both to the patient's condition during the procedure and to their medical history.[
Reinsertion of the stylet may decrease the rate of post lumbar puncture headaches.
Thoracocentesis or Pleural Tap
Thoracentesis (pronounced /ˌθɔrəsɨnˈtiːsɨs/) (also known as thoracocentesis or pleural tap) is an invasive procedure to remove fluid or air from the pleural space for diagnostic or therapeutic purposes. A cannula, or hollow needle, is carefully introduced into the thorax, generally after administration of local anesthesia. The procedure was first described in 1852.
The recommended location varies depending upon the source. It is critical that the patient holds their breath to avoid piercing the lung. Some sources recommend the midaxillary line, in the ninth intercostal space.
Chest X-ray showing a left-sided pleural effusion (right side of image). This can be treated with thoracentesis.
The illustration shows a person having thoracentesis. The person sits upright and leans on a table. Excess fluid from the pleural space is drained into a bag.
Indications
This procedure is indicated when unexplained fluid accumulates in the chest cavity outside the lung. In more than 90% of cases analysis of pleural fluid yields clinically useful information. If a large amount of fluid is present, then this procedure can also be used therapeutically to remove that fluid and improve patient comfort and lung function.
The most common causes of pleural effusions are cancer, congestive heart failure, pneumonia, and recent surgery. In countries where tuberculosis is common, this is also a common cause of pleural effusions.
When cardiopulmonary status is compromised (i.e. when the fluid or air has its repercussions on the function of heart and lungs), due to air (significant pneumothorax), fluid (pleural fluid) or blood (hemothorax) outside the lung, then this procedure is usually replaced with tube thoracostomy, the placement of a large tube in the pleural space.
Contraindications
An uncooperative patient or a coagulation disorder that can not be corrected are absolute contraindications.
Relative contraindications include cases in which the site of insertion has known bullous disease (e.g. emphysema), use of positive end-expiratory pressure (PEEP, see mechanical ventilation) and only one functioning lung (due to diminished reserve). The aspiration should not exceed 1L as there is a risk of development of pulmonary edema.
Complications
Major complications are pneumothorax (3-30%), hemopneumothorax, hemorrhage, hypotension (low blood pressure due to a vasovagal response) and reexpansion pulmonary edema.
Minor complications include a dry tap (no fluid return), subcutaneous hematoma or seroma, anxiety, dyspnea and cough (after removing large volume of fluid).
The use of ultrasound for needle guidance can minimize the complication rate.
Interpretation of pleural fluid analysis
Several diagnostic tools are available to determine the etiology of pleural fluid.
Transudate versus exudate
First the fluid is either transudate or exudate.
A transudate is defined as pleural fluid to serum total protein ratio of less than 0.5, pleural fluid to serum LDH ratio < 0.6, and absolute pleural fluid LDH < 200 IU or < 2/3 of the normal serum.
An exudate is any fluid that filters from the circulatory system into lesions or areas of inflammation. It can apply to plants as well as animals. Its composition varies but generally includes water and the dissolved solutes of the main circulatory fluid such as sap or blood. In the case of blood: it will contain some or all plasma proteins, white blood cells, platelets and (in the case of local vascular damage) red blood cells.
Exudate
• hemorrhage
• Infection
• Inflammation
• Malignancy
• Iatrogenic
• Connective tissue disease
• Endocrine disorders
• Lymphatic disorders vs Constrictive pericarditis
Transudate
• Congestive heart failure
• Nephrotic syndrome
• Hypoalbuminemia
• Cirrhosis
• Atelectasis
• trapped lung
• Peritoneal dialysis
• Superior vena cava obstruction
Amylase
A high amylase level (twice the serum level or the absolute value is greater than 160 Somogy units) in the pleural fluid is indicative of either acute or chronic pancreatitis, pancreatic pseudocyst that has dissected or ruptured into the pleural space, cancer or esophageal rupture.
Glucose
This is considered low if pleural fluid value is less than 50% of normal serum value. The differential diagnosis for this is:
• rheumatoid effusion.The levels are characteristically low (<15 mg/dL).
• lupus effusion
• bacterial empyema
• malignancy
• tuberculosis
• esophageal rupture (Boerhaave syndrome)
pH
Normal pleural fluid pH is approximately 7.60. A pleural fluid pH below 7.30 with normal arterial blood pH has the same differential diagnosis as low pleural fluid glucose.
Triglyceride and cholesterol
Chylothorax (fluid from lymph vessels leaking into the pleural cavity) may be identified by determining triglyceride and cholesterol levels, which are relatively high in lymph. A triglyceride level over 110 mg/dl and the presence of chylomicrons indicate a chylous effusion. The appearance is generally milky but can be serous.
The main cause for chylothorax is rupture of the thoracic duct, most frequently as a result of trauma or malignancy (such as lymphoma).
Cell count and differential
The number of white blood cells can give an indication of infection. The specific subtypes can also give clues as to the type on infection. The amount of red blood cells are an obvious sign of bleeding.
Cultures and stains
If the effusion is caused by infection, microbiological culture may yield the infectious organism responsible for the infection, sometimes before other cultures (e.g. blood cultures and sputum cultures) become positive. A Gram stain may give a rough indication of the causative organism. A Ziehl-Neelsen stain may identify tuberculosis or other mycobacterial diseases.
Cytology
Cytology is an important tool in identifying effusions due to malignancy. The most common causes for pleural fluid are lung cancer, metastasis from elsewhere and mesothelioma. The latter often presents with an effusion. Normal cytology results do not reliably rule out malignancy, but make the diagnosis more unlikely.
Abdominal tap
Alternative Names: Peritoneal tap; Paracentesis
An abdominal tap is a procedure used to remove fluid from the abdomen.
How the Test is Performed
This test may be done in an office setting, treatment room, or hospital.
The puncture site will be cleaned and shaved, if necessary. You then receive a local numbing medicine. The tap needle is inserted 1 - 2 inches into the abdomen. Sometimes a small cut is made to help insert the needle. The fluid is pulled out into a syringe.
The needle is removed. A dressing is placed on the puncture site. If a cut was made, one or two stitches may be used to close it.
There are two kinds of abdominal taps:
• Diagnostic tap -- a small amount of fluid is taken and sent to the laboratory for testing
• Large volume tap -- several liters may be removed to relieve abdominal pain and fluid buildup
How to Prepare for the Test
Let your health care provider know if you:
• Have any allergies to medications or numbing medicine
• Are taking any medications (including herbal remedies)
• Have any bleeding problems
• Might be pregnant
Infants and children:
The preparation you can provide for this test depends on your child's age, previous experience, and level of trust. For general information regarding how you can prepare your child, see the following topics:
• Infant test/procedure preparation (birth - 1 year)
• Toddler test/procedure preparation (1 - 3 years)
• Preschooler test/procedure preparation (3 - 6 years)
• School age test/procedure preparation (6 - 12 years)
• Adolescent test/procedure preparation (12 - 18 years)
How the Test Will Feel
You may feel a stinging sensation from the numbing medicine, or pressure as the needle is inserted.
If a large amount of fluid is taken out, you may feel dizzy or light-headed. Tell the health care provider if you feel dizzy.
Why the Test is Performed
Normally, the abdomen contains only a small amount of fluid. In certain conditions, large amounts of fluid can build up in the abdomen.
An abdominal tap may be done to diagnose the cause of fluid buildup. It may also be done to diagnose infected abdominal fluid, or to remove a large amount of fluid to reduce abdominal pain.
Normal Results
Normally, there should be little or no fluid in the abdomen.
What Abnormal Results Mean
An examination of abdominal fluid may show:
• Appendicitis
• Cirrhosis of the liver
• Damaged bowel
• Heart disease
• Infection
• Kidney disease
• Pancreatic disease
• Tumor (cancerous or noncancerous)
Risks
There is a slight chance of the needle puncturing the bowel, bladder, or a blood vessel in the abdomen. If a large quantity of fluid is removed, there is a slight risk of lowered blood pressure and kidney failure. There is also a slight chance of infection.
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Bone marrow examination
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A Wright's stained bone marrow aspirate smear from a patient with leukemia.
Bone marrow examination refers to the pathologic analysis of samples of bone marrow obtained by bone marrow biopsy (often called a trephine biopsy) and bone marrow aspiration. Bone marrow examination is used in the diagnosis of a number of conditions, including leukemia, multiple myeloma, anemia, and pancytopenia. The bone marrow produces the cellular elements of the blood, including platelets, red blood cells and white blood cells. While much information can be gleaned by testing the blood itself (drawn from a vein by phlebotomy), it is sometimes necessary to examine the source of the blood cells in the bone marrow to obtain more information on hematopoiesis; this is the role of bone marrow aspiration and biopsy.
Components of the procedure
A bone marrow harvest.
A volunteer donating bone marrow for scientific research.
Bone marrow samples can be obtained by aspiration and trephine biopsy. Sometimes, a bone marrow examination will include both an aspirate and a biopsy. The aspirate yields semi-liquid bone marrow, which can be examined by a pathologist under a light microscope as well as analyzed by flow cytometry, chromosome analysis, or polymerase chain reaction (PCR). Frequently, a trephine biopsy is also obtained, which yields a narrow, cylindrically shaped solid piece of bone marrow, 2mm wide and 2 cm long (60 μL), which is examined microscopically (sometimes with the aid of immunohistochemistry) for cellularity and infiltrative processes. An aspiration, using a 20 mL syringe, yields approximately 300 μL of bone marrow.[1] A volume greater than 300 μL is not recommended, since it may dilute the sample with peripheral blood.[1]
Comparison
Aspiration Biopsy
Advantages • Fast
• Gives relative quantity of different cell types
• Gives material to further study, e.g. molecular genetics and flow cytometry
• Gives cell and stroma constitution
• Represents all cells
• Explains cause of "dry tap" (aspiration gives no blood cells)
Drawbacks Doesn't represent all cells Slow processing
Aspiration doesn't always represent all cells since, as some such as lymphoma stick to the trabecula, and would thus be missed by a simple aspiration.
Site of procedure
Bone marrow aspiration and trephine biopsy are usually performed on the back of the hipbone, or posterior iliac crest. However, an aspirate can also be obtained from the sternum (breastbone). A trephine biopsy should never be performed on the sternum, due to the risk of injury to blood vessels, lungs or the heart.
How the test is performed
A needle used for bone marrow aspiration, with removable stylet.
A bone marrow biopsy may be done in a health care provider's office or in a hospital. Informed consent for the procedure is typically required. The patient is asked to lie on his or her abdomen (prone position) or on his/her side (lateral decubitus position). The skin is cleansed, and a local anesthetic such as lidocaine is injected to numb the area. Patients may also be pretreated with analgesics and/or anti-anxiety medications, although this is not a routine practice.
Typically, the aspirate is performed first. An aspirate needle is inserted through the skin until it abuts the bone. Then, with a twisting motion, the needle is advanced through the bony cortex (the hard outer layer of the bone) and into the marrow cavity. Once the needle is in the marrow cavity, a syringe is attached and used to aspirate ("suck out") liquid bone marrow. A twisting motion is performed during the aspiration to avoid excess content of blood in the sample, which might be the case if an excessively large sample from one single point is taken.
Subsequently, the biopsy is performed if indicated. A different, larger trephine needle is inserted and anchored in the bony cortex. The needle is then advanced with a twisting motion and rotated to obtain a solid piece of bone marrow. This piece is then removed along with the needle. The entire procedure, once preparation is complete, typically takes 10–15 minutes.
If several samples are taken, the needle is removed between the samples to avoid blood coagulation.
After the procedure
After the procedure is complete, the patient is typically asked to lie flat for 5–10 minutes to provide pressure over the procedure site. After that, assuming no bleeding is observed, the patient can get up and go about their normal activities. Paracetamol (acetaminophen) or other simple analgesics can be used to ease soreness, which is common for 2–3 days after the procedure. Any worsening pain, redness, fever, bleeding or swelling may suggest a complication. Patients are also advised to avoid washing the procedure site for at least 24 hours after the procedure is completed.
Contraindications
There are few contraindications to bone marrow examination. The only absolute reason to avoid performing a bone marrow examination is the presence of a severe bleeding disorder which may lead to serious bleeding after the procedure. If there is a skin or soft tissue infection over the hip, a different site should be chosen for bone marrow examination. Bone marrow aspiration and biopsy can be safely performed even in the setting of extreme thrombocytopenia (low platelet count).
Complications
While mild soreness lasting 12–24 hours is common after a bone marrow examination, serious complications are extremely rare. In a large review, an estimated 55,000 bone marrow examinations were performed, with 26 serious adverse events (0.05%), including one fatality. The same author collected data on over 19,000 bone marrow examinations performed in the United Kingdom in 2003, and found 16 adverse events (0.08% of total procedures), the most common of which was bleeding. In this report, complications, while rare, were serious in individual cases.
Tracheotomy
Completed tracheotomy:
1 - Vocal cords
2 - Thyroid cartilage
3 - Cricoid cartilage
4 - Tracheal cartilages
5 - Balloon cuff
Tracheotomy and tracheostomy are surgical procedures on the neck to open a direct airway through an incision in the trachea (the windpipe). They are performed by emergency physicians, and surgeons. Both surgical and percutaneous techniques are now widely used.
While tracheostomy may have possibly been portrayed on ancient Egyptian tablets,[1] the first correct description of the tracheotomy operation for patients who are suffocating was described by Ibn Zuhr in the 12th century,[2] and the currently used surgical tracheostomy technique was described in 1909 by Dr. Chevalier Jackson of Pittsburgh, Pennsylvania.
Terminology
Tracheotomy, from the Greek root tom- meaning "to cut," refers to the procedure of cutting into the trachea and is an emergency procedure.[3]
A tracheostomy, from the root stom- meaning "mouth," refers to the making of a semi-permanent or permanent opening, and to the opening itself.
Some sources offer different definitions of the above terms. Part of the ambiguity is due to the uncertainty of the intended permanence of the stoma at the time it is created.[4]
Uses of tracheotomy
The conditions in which a tracheotomy may be used are:
• Acute setting - maxillofacial injuries, large tumors of the head and neck, congenital tumors, e.g. branchial cyst, acute inflammation of head and neck, and
• Chronic / elective setting - when there is need for long term mechanical ventilation and tracheal toilet, e.g. comatose patients, surgery to the head and neck.
In emergency settings, in the context of failed endotracheal intubation or where intubation is contraindicated, cricothyroidotomy or mini-tracheostomy may be performed in preference to a tracheostomy.
Tracheotomy procedure
1. Curvilinear skin incision along relaxed skin tension lines (RSTL) between sternal notch and cricoid cartilage.
2. Midline vertical incision dividing strap muscles.
3. Division of thyroid isthmus between ligatures.
4. Elevation of cricoid with cricoid hook.
5. Placement of tracheal incision. An inferior based flap, or Björk flap, (through second and third tracheal rings) is commonly used. The flap is then sutured to the inferior skin margin. Alternatives include a vertical tracheal incision (pediatric) or excision of an ellipse of anterior tracheal wall.
6. Insert tracheostomy tube (with concomitant withdrawal of endotracheal tube), inflate cuff, secure with tape around neck or stay sutures.
7. Connect ventilator tubing.
It is also possible to make a simple vertical incision between tracheal rings (typically 2nd and 3rd) for the incision. Rear end flaps may produce more intratracheal granulation tissue at the site of the incisions, making it less favorable to some surgeons.
Percutaneous tracheotomy procedure
1. Curvilinear skin incision along relaxed skin tension lines between sternal notch and cricoid cartilage.
2. Midline blunt dissection down to the trachea (optional depending on technique).
3. Insertion of 14-gauge plastic cannula and needle with fluid filled syringe attached into trachea. Aspiration of air confirms correct placement of the tip in the trachea.
4. Removal of needle leaving cannula in place.
5. Insertion of soft tipped guide wire into trachea through cannula.
6. Removal of cannula leaving guide wire in place.
7. Tracheal dilatation is now undertaken - different techniques do this in different ways.
1. Ciaglia - the sequential insertion and removal of a series (usually 4-5) of increasing larger dilators over the wire into the trachea.
2. Griggs - insertion of a specially designed pair of guide-wire forceps along the wire into the trachea and then are opened to complete the dilation in one step.
3. Rhino - insertion of a single large tapered dilator over a plastic guidewire reinforcement.
4. Frova Percutwist - insertion of a specially designed screw of increasing diameter which rotates to create the dilatation.
8. Insert tracheostomy tube (with concomitant withdrawal of endotracheal tube), inflate cuff, secure with tape around neck or stay sutures.
9. Connect ventilator tubing.
Risks
During the procedure, there is a risk of damaging the recurrent laryngeal nerves. These nerves control the vocal cords. If one of the nerves is damaged a patient will probably have a problem with his/her voice; if both of the nerves are damaged, the patient will lose his/her speech. This risk of nerve damage is the reason emergency tracheotomies are performed higher up, in the larynx and why tracheotomies have to be done in hospital under anesthetic. Professor Stephen Hawking lost his speech due to a tracheotomy after contracting pneumonia.
Moreover, if the recurrent laryngeal nerve is damaged, the patient will have trouble controlling the flow of air through the rima glottidis, thus ultimately leading to inhibited breathing or suffocation.
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