Thursday, August 14, 2008
DDS by Bharesh Dedhia
Dialysis Disequilibrium syndrome by Bharesh Dedhia
The Dialysis disequilibrium syndrome (DDS) is a central nervous system disorder that remains an important clinical problem in dialysis patients. It is characterized by neurologic symptoms of varying severity that are thought to be due primarily to cerebral edema. New patients just being started on hemodialysis are at greatest risk, particularly if the BUN is markedly elevated (above 175 mg/dL or 60 mmol/L). Other predisposing factors include severe metabolic acidosis, older age, pediatric patients, and the presence of other central nervous system disease such as a preexisting seizure disorder.
CLINICAL MANIFESTATIONS
The classic DDS refers to acute symptoms developing during or immediately after hemodialysis. Early findings include headache, nausea, disorientation, restlessness, blurred vision, and asterixis. More severely affected patients progress to confusion, seizures, coma, and even death. It is now recognized, however, that many milder signs and symptoms associated with dialysis such as muscle cramps, anorexia, and dizziness developing near the end of a dialysis treatment are also part of this syndrome. The incidence of DDS varies according to the patient population and the attention paid to the preventive measures described below. Severe DDS is now rare in adults because of the standard use of the preventive recommendations made below. However, children may remain at increased risk. A retrospective analysis of 180 children and adolescents on maintenance dialysis foundthat 13 (7 percent) had dialysis-associated seizures. All but one of these patients were treated with hemodialysis. The development of the above symptoms during dialysis is strongly suggestive of DDS. Nevertheless, there are a number of other disorders that must be excluded including uremia itself, subdural hematoma, metabolic disturbances (hyponatremia, hypoglycemia), and drug-induced encephalopathy. Drug accumulation is a particular problem in renal failure with drugs that are normally excreted by the kidney.
PATHOGENESIS
The symptoms of DDS are caused by water movement into the brain, leading to cerebral edema. Two theories have been proposed to explain why this occurs: a reverse osmotic shift induced by urea ; and a fall in cerebral intracellular pH. Hemodialysis rapidly removes small solutes such as urea, particularly in patients who have marked azotemia. The reduction in BUN lowers the plasma osmolality, thereby creating a transient osmotic gradient that promotes water movement into the cells. In the brain, this water shift produces cerebral edema and a variable degree of acute neurologic dysfunction. The loss of extracellular water can also cause extracellular volume depletion which can contribute to the development of hypotension. The pathogenetic importance of urea in the DDS has been demonstrated by experiments in uremic rats. In one report, for example, rapid dialysis lowered the BUN from 200 to 95 mg/dL (72 to 34 mmol/L) in 90 minutes . This change was associated with a six percent increase in brain water. Neither undialyzed rats nor those rats dialyzed against a bath to which urea was added to prevent a fall in BUN developed cerebral edema. Furthermore, the retention of brain urea appears to be account for most of the increase in brain water. Urea is generally considered an "ineffective" osmole, because of its ability to permeate cell membranes. However, this effect may take several hours to reach completion. Thus, there is insufficient time for urea equilibration when hemodialysis rapidly reduces the BUN; as a result, urea transiently acts as an effective osmole, promoting water movement into the brain. In the above experiments, for example, the 53 percent acute reduction in BUN was only associated with a 13 percent reduction in brain urea nitrogen. Intracerebral acidosis Some investigators have suggested that the reverse urea effect cannot account for the development of cerebral edema in the DDS, since urea movement out of the brain is sufficiently rapid to prevent a large osmotic gradient between the brain and extracellular fluid . They have proposed that a decrease in cerebral intracellular pH, occurring via an uncertain mechanism, is of primary importance. Both displacement of bound sodium and potassium by the excess hydrogen ions and enhanced production of organic acids can increase intracellular osmolality and promote water movement into the brain. However, an increase in brain organic osmolytes has not been confirmed in all studies. In most reports, the reverse urea effect appears sufficient to explain most of dialysis disequilibrium.
TREATMENT
Prevention is the mainstay of therapy in the DDS, particularly in new dialysis patients who are at highest risk. The initial dialyses should be gentle, but repeated frequently. The aim is a gradual reduction in BUN, which will be protective but may not prevent mild symptoms such as headache and malaise. Slow urea removal can be achieved by one of the following methods: With hemodialysis, therapy can be initiated with two hours of dialysis at a relatively low blood flow rate of 150 to 250 mL/min with a small surface area dialyzer. This regimen, which is repeated daily for three or four days, is different from the standard every other day four-hour regimen at high flow rates. If the patient shows no signs of DDS, the blood flow rate can be increased by 50 mL/min per treatment (up to 300 to 400 mL/min) and the duration of dialysis can be increased in 30 minute increments (up to four or more hours, as necessary for adequate solute removal). Patients who also have marked fluid overload can be treated with ultrafiltration (which removes less urea per unit time) followed by a short period of hemodialysis. The patient can be started on peritoneal dialysis in which the low rate of peritoneal blood flow results in a urea clearance per unit time that is much lower than that with hemodialysis. The DDS has not been reported with continuous peritoneal dialysis. Some physicians recommend prophylactic phenytoin (1000 mg loading dose followed by 300 mg/day until uremia is controlled) and/or the administration of 12.5 g of hypertonic mannitol intravenously every hour of dialysis in high-risk patients with marked azotemia (BUN above 150 to 200 mg/dL [54 to 71 mmol/L]) or an underlying alteration in mental status. Symptoms of DDS are self-limited and usually dissipate within several hours. Severe DDS with seizures can be reversed more rapidly by raising the plasma osmolality with either 5 mL of 23 percent saline or 12.5 g of hypertonic mannitol.Bharesh Dedhia
The Dialysis disequilibrium syndrome (DDS) is a central nervous system disorder that remains an important clinical problem in dialysis patients. It is characterized by neurologic symptoms of varying severity that are thought to be due primarily to cerebral edema. New patients just being started on hemodialysis are at greatest risk, particularly if the BUN is markedly elevated (above 175 mg/dL or 60 mmol/L). Other predisposing factors include severe metabolic acidosis, older age, pediatric patients, and the presence of other central nervous system disease such as a preexisting seizure disorder.
CLINICAL MANIFESTATIONS
The classic DDS refers to acute symptoms developing during or immediately after hemodialysis. Early findings include headache, nausea, disorientation, restlessness, blurred vision, and asterixis. More severely affected patients progress to confusion, seizures, coma, and even death. It is now recognized, however, that many milder signs and symptoms associated with dialysis such as muscle cramps, anorexia, and dizziness developing near the end of a dialysis treatment are also part of this syndrome. The incidence of DDS varies according to the patient population and the attention paid to the preventive measures described below. Severe DDS is now rare in adults because of the standard use of the preventive recommendations made below. However, children may remain at increased risk. A retrospective analysis of 180 children and adolescents on maintenance dialysis foundthat 13 (7 percent) had dialysis-associated seizures. All but one of these patients were treated with hemodialysis. The development of the above symptoms during dialysis is strongly suggestive of DDS. Nevertheless, there are a number of other disorders that must be excluded including uremia itself, subdural hematoma, metabolic disturbances (hyponatremia, hypoglycemia), and drug-induced encephalopathy. Drug accumulation is a particular problem in renal failure with drugs that are normally excreted by the kidney.
PATHOGENESIS
The symptoms of DDS are caused by water movement into the brain, leading to cerebral edema. Two theories have been proposed to explain why this occurs: a reverse osmotic shift induced by urea ; and a fall in cerebral intracellular pH. Hemodialysis rapidly removes small solutes such as urea, particularly in patients who have marked azotemia. The reduction in BUN lowers the plasma osmolality, thereby creating a transient osmotic gradient that promotes water movement into the cells. In the brain, this water shift produces cerebral edema and a variable degree of acute neurologic dysfunction. The loss of extracellular water can also cause extracellular volume depletion which can contribute to the development of hypotension. The pathogenetic importance of urea in the DDS has been demonstrated by experiments in uremic rats. In one report, for example, rapid dialysis lowered the BUN from 200 to 95 mg/dL (72 to 34 mmol/L) in 90 minutes . This change was associated with a six percent increase in brain water. Neither undialyzed rats nor those rats dialyzed against a bath to which urea was added to prevent a fall in BUN developed cerebral edema. Furthermore, the retention of brain urea appears to be account for most of the increase in brain water. Urea is generally considered an "ineffective" osmole, because of its ability to permeate cell membranes. However, this effect may take several hours to reach completion. Thus, there is insufficient time for urea equilibration when hemodialysis rapidly reduces the BUN; as a result, urea transiently acts as an effective osmole, promoting water movement into the brain. In the above experiments, for example, the 53 percent acute reduction in BUN was only associated with a 13 percent reduction in brain urea nitrogen. Intracerebral acidosis Some investigators have suggested that the reverse urea effect cannot account for the development of cerebral edema in the DDS, since urea movement out of the brain is sufficiently rapid to prevent a large osmotic gradient between the brain and extracellular fluid . They have proposed that a decrease in cerebral intracellular pH, occurring via an uncertain mechanism, is of primary importance. Both displacement of bound sodium and potassium by the excess hydrogen ions and enhanced production of organic acids can increase intracellular osmolality and promote water movement into the brain. However, an increase in brain organic osmolytes has not been confirmed in all studies. In most reports, the reverse urea effect appears sufficient to explain most of dialysis disequilibrium.
TREATMENT
Prevention is the mainstay of therapy in the DDS, particularly in new dialysis patients who are at highest risk. The initial dialyses should be gentle, but repeated frequently. The aim is a gradual reduction in BUN, which will be protective but may not prevent mild symptoms such as headache and malaise. Slow urea removal can be achieved by one of the following methods: With hemodialysis, therapy can be initiated with two hours of dialysis at a relatively low blood flow rate of 150 to 250 mL/min with a small surface area dialyzer. This regimen, which is repeated daily for three or four days, is different from the standard every other day four-hour regimen at high flow rates. If the patient shows no signs of DDS, the blood flow rate can be increased by 50 mL/min per treatment (up to 300 to 400 mL/min) and the duration of dialysis can be increased in 30 minute increments (up to four or more hours, as necessary for adequate solute removal). Patients who also have marked fluid overload can be treated with ultrafiltration (which removes less urea per unit time) followed by a short period of hemodialysis. The patient can be started on peritoneal dialysis in which the low rate of peritoneal blood flow results in a urea clearance per unit time that is much lower than that with hemodialysis. The DDS has not been reported with continuous peritoneal dialysis. Some physicians recommend prophylactic phenytoin (1000 mg loading dose followed by 300 mg/day until uremia is controlled) and/or the administration of 12.5 g of hypertonic mannitol intravenously every hour of dialysis in high-risk patients with marked azotemia (BUN above 150 to 200 mg/dL [54 to 71 mmol/L]) or an underlying alteration in mental status. Symptoms of DDS are self-limited and usually dissipate within several hours. Severe DDS with seizures can be reversed more rapidly by raising the plasma osmolality with either 5 mL of 23 percent saline or 12.5 g of hypertonic mannitol.Bharesh Dedhia
Fulminant Hepatic Failure (FHF) by Bharesh Dedhia
Bharesh Dedhia
Liver disease is a major source of morbidity and mortality in the intensive care unit . Cirrhotic patients admitted to the medical ICU have increased mortality (40 to 90%) and a poor prognosis.Fulminant hepatic failure is a clinical syndrome characterized by the rapid onset of hepatic encephalopathy in conjunction with a marked decline in hepatic synthetic function within 28 days of the onset of symptoms in those without a history of chronic liver disease .The National Institutes of Health Acute Liver Failure Study Group reported the etiology of fulminant hepatic failure in 308 patients as follows: acetaminophen hepato-toxicity (39%), idiosyncratic drug reaction (13%), hepatitis B (6%), hepatitis A (6%), and indeterminate cause (17%) (3).
Overall survival is poor without liver transplantation, with a reported mortality of 90 to 97% .The advent of liver transplantation and aggressive medical care in the ICU has improved the mortality rate .
Diagnosis
Hepatic encephalopathy and severe coagulopathy are the hallmark features of fulminant hepatic failure . Severe coagulopathy often precedes evolution of hepatic encephalopathy to coma. Patients with fulminant hepatic failure can rapidly progress from mild hepatic encephalopathy to deep coma .As soon as the diagnosis is made, it is important to establish the cause. Certain etiologies demand immediate specific treatment, including N-acetylcysteine for acetaminophen ingestion, penicillin for Amanita mushroom poisoning, delivery of the infant in acute fatty liver of pregnancy, or zinc and trientine therapy for Wilson's disease. Patients should be admitted to the ICU and transferred to a transplantation center, given that liver transplantation is the only effective therapy for this devastating disease .
Management
Management starts with supportive measures including nutrition (amino acids, lipids, glucose, and essential elements), electrolyte balance, frequent glucose monitoring .Infection in patients with fulminant hepatic failure is a major source of mortality, as 44 to 80% of patients with fulminant hepatic failure develop bacterial infections. Empiric, broad-spectrum antibiotics should be initiated on clinical suspicion of infection .Cerebral edema is a common complication of fulminant hepatic failure, occurring in up to 80% of patients with Grade IV coma, but requires a high level of clinical suspicion. The diagnosis may be difficult to establish as head computed tomography scan is insensitive, being useful only to rule out hemorrhage, and clinical signs of cerebral edema, such as decerebrate posturing, systemic hypertension, and pupillary abnormalities, are typically observed only in advanced disease. Cerebral edema often leads to intracranial hypertension and subsequent herniation of the cerebral uncus, cerebral ischemic injury, and death. Intracranial hypertension can also cause a reduction in the cerebral perfusion pressure (mean arterial pressure minus intracranial pressure), which may produce cerebral ischemia. A cerebral perfusion pressure of more than 60 mm Hg is crucial to maintain intact neurologic function .Direct intracranial pressure monitoring is recommended in patients suspected of cerebral edema or intracranial hypertension, with a target intracranial pressure of less than 20 mm Hg .The placement of extradural intracranial pressure monitors is considered safer than subdural catheters. Recombinant Factor VIIa can reverse coagulopathy in those patients requiring intracranial pressure monitor placement , and may prove preferable to fresh frozen plasma if additional studies are confirmatory. The patient's head should be elevated 10 to 20°. Maneuvers that increase intracranial pressure, such as tracheal suction or high positive end-expiratory pressure, should be avoided. Use of sedation is usually avoided so that mental status may be assessed. However, an agitated patient with Grade III coma may require the use of short-acting benzodiazepenes, the preferred agents .Mannitol is first-line therapy for treating cerebral edema and intracranial hypertension, administered at 0.3 to 0.4 g/kg body weight. In patients with renal failure, mannitol may accumulate in astrocytes and cause increased rebound swelling .Thiopental may be used in this setting (250 mg over 15 minutes). Hyperventilation may also reduce cerebral edema, but it is effective only for a few hours.In one case series, seven patients with fulminant hepatic failure were given propofol for deteriorating cerebral edema .A decrease in intracranial pressure was seen in five patients. However, only three survived, with one undergoing liver transplantation. Additional studies are needed before a recommendation to use propofol in this setting can be made. Another therapeutic adjunct, moderate hypothermia to 32-33°C, may be useful in decreasing intracranial pressure as a bridge to liver transplantation ., or while transplantation is being performed .Liver transplantation offers the best long-term survival with an overall, posttransplantation 1-year survival of about 60% .Unfortunately, prediction of the need for transplantation remains problematic. The King's College Hospital criteria are the most widely used prognostic indicator for survival in fulminant hepatic failure .These criteria include an arterial pH of less than 7.30 after adequate fluid resuscitation, or the combination of a prothrombin time greater than 100 seconds, a creatinine level greater than 3.3 mg/dl, and Grade III or IV encephalopathy. These criteria exhibit a sensitivity, specificity, positive predictive value, and negative predictive value of 55, 94, 87, and 78%, respectively. A metaanalysis investigated several prognostic criteria for determining the need for liver transplant in acetaminophen-induced fulminant hepatic failure including King's College criteria, pH, prothombin time, Factor V levels, and creatinine, but found that none of these was sufficiently sensitive in predicting the need for liver transplantation .Arterial blood lactate greater than 3.5 mmol/L 4 hours after presentation to the hospital has been shown to have a sensitivity of 67%, a specificity of 95%, a positive likelihood ratio of 13%, and a negative likelihood ratio of 35% for survival in acetaminophen-induced fulminant hepatic failure .
Advances in Artificial and Bioartificial Support Systems
Short-term extracorporeal support for patients with fulminant hepatic failure may ultimately serve to improve overall survival and provide support as a bridge to liver transplantation, but remains experimental. A metaanalysis of artificial and bioartificial support systems for fulminant hepatic failure examined a total of 8 randomized controlled trials, involving 139 patients, and found no improvement in mortality compared with standard supportive care (relative risk, 0.95; 95% confidence interval, 0.71-1.29) .In addition, the interventions were not found to be useful as a bridge to liver transplantation (relative risk, 0.60; 95% confidence interval, 0.29-1.23). The support systems appeared to have an increased risk of bleeding associated with their use. A future option is hepatocyte transplantation. In one series, three of six patients with fulminant hepatic failure survived between 14 and 52 days after transplantation of 10^sup 10^ human hepatocytes .To date, no randomized, controlled studies have examined this therapeutic option.
Recommendations
Once the diagnosis is made, all necessary supportive measures should be employed in an ICU setting. Neurologic evaluation and glucose monitoring should be performed frequently. Coagulopathy should be corrected when there is overt bleeding or an invasive procedure is planned. An emergent head computed tomography scan should be performed if there is a change in mental status or signs of increased intracranial pressure. Intracranial pressure monitoring is recommended to maintain an adequate cerebral perfusion pressure of greater than 60 mm Hg. Currently, liver transplantation offers the best long-term survival in patients likely to die of fulminant hepatic failure.
Bharesh Dedhia
Liver disease is a major source of morbidity and mortality in the intensive care unit . Cirrhotic patients admitted to the medical ICU have increased mortality (40 to 90%) and a poor prognosis.Fulminant hepatic failure is a clinical syndrome characterized by the rapid onset of hepatic encephalopathy in conjunction with a marked decline in hepatic synthetic function within 28 days of the onset of symptoms in those without a history of chronic liver disease .The National Institutes of Health Acute Liver Failure Study Group reported the etiology of fulminant hepatic failure in 308 patients as follows: acetaminophen hepato-toxicity (39%), idiosyncratic drug reaction (13%), hepatitis B (6%), hepatitis A (6%), and indeterminate cause (17%) (3).
Overall survival is poor without liver transplantation, with a reported mortality of 90 to 97% .The advent of liver transplantation and aggressive medical care in the ICU has improved the mortality rate .
Diagnosis
Hepatic encephalopathy and severe coagulopathy are the hallmark features of fulminant hepatic failure . Severe coagulopathy often precedes evolution of hepatic encephalopathy to coma. Patients with fulminant hepatic failure can rapidly progress from mild hepatic encephalopathy to deep coma .As soon as the diagnosis is made, it is important to establish the cause. Certain etiologies demand immediate specific treatment, including N-acetylcysteine for acetaminophen ingestion, penicillin for Amanita mushroom poisoning, delivery of the infant in acute fatty liver of pregnancy, or zinc and trientine therapy for Wilson's disease. Patients should be admitted to the ICU and transferred to a transplantation center, given that liver transplantation is the only effective therapy for this devastating disease .
Management
Management starts with supportive measures including nutrition (amino acids, lipids, glucose, and essential elements), electrolyte balance, frequent glucose monitoring .Infection in patients with fulminant hepatic failure is a major source of mortality, as 44 to 80% of patients with fulminant hepatic failure develop bacterial infections. Empiric, broad-spectrum antibiotics should be initiated on clinical suspicion of infection .Cerebral edema is a common complication of fulminant hepatic failure, occurring in up to 80% of patients with Grade IV coma, but requires a high level of clinical suspicion. The diagnosis may be difficult to establish as head computed tomography scan is insensitive, being useful only to rule out hemorrhage, and clinical signs of cerebral edema, such as decerebrate posturing, systemic hypertension, and pupillary abnormalities, are typically observed only in advanced disease. Cerebral edema often leads to intracranial hypertension and subsequent herniation of the cerebral uncus, cerebral ischemic injury, and death. Intracranial hypertension can also cause a reduction in the cerebral perfusion pressure (mean arterial pressure minus intracranial pressure), which may produce cerebral ischemia. A cerebral perfusion pressure of more than 60 mm Hg is crucial to maintain intact neurologic function .Direct intracranial pressure monitoring is recommended in patients suspected of cerebral edema or intracranial hypertension, with a target intracranial pressure of less than 20 mm Hg .The placement of extradural intracranial pressure monitors is considered safer than subdural catheters. Recombinant Factor VIIa can reverse coagulopathy in those patients requiring intracranial pressure monitor placement , and may prove preferable to fresh frozen plasma if additional studies are confirmatory. The patient's head should be elevated 10 to 20°. Maneuvers that increase intracranial pressure, such as tracheal suction or high positive end-expiratory pressure, should be avoided. Use of sedation is usually avoided so that mental status may be assessed. However, an agitated patient with Grade III coma may require the use of short-acting benzodiazepenes, the preferred agents .Mannitol is first-line therapy for treating cerebral edema and intracranial hypertension, administered at 0.3 to 0.4 g/kg body weight. In patients with renal failure, mannitol may accumulate in astrocytes and cause increased rebound swelling .Thiopental may be used in this setting (250 mg over 15 minutes). Hyperventilation may also reduce cerebral edema, but it is effective only for a few hours.In one case series, seven patients with fulminant hepatic failure were given propofol for deteriorating cerebral edema .A decrease in intracranial pressure was seen in five patients. However, only three survived, with one undergoing liver transplantation. Additional studies are needed before a recommendation to use propofol in this setting can be made. Another therapeutic adjunct, moderate hypothermia to 32-33°C, may be useful in decreasing intracranial pressure as a bridge to liver transplantation ., or while transplantation is being performed .Liver transplantation offers the best long-term survival with an overall, posttransplantation 1-year survival of about 60% .Unfortunately, prediction of the need for transplantation remains problematic. The King's College Hospital criteria are the most widely used prognostic indicator for survival in fulminant hepatic failure .These criteria include an arterial pH of less than 7.30 after adequate fluid resuscitation, or the combination of a prothrombin time greater than 100 seconds, a creatinine level greater than 3.3 mg/dl, and Grade III or IV encephalopathy. These criteria exhibit a sensitivity, specificity, positive predictive value, and negative predictive value of 55, 94, 87, and 78%, respectively. A metaanalysis investigated several prognostic criteria for determining the need for liver transplant in acetaminophen-induced fulminant hepatic failure including King's College criteria, pH, prothombin time, Factor V levels, and creatinine, but found that none of these was sufficiently sensitive in predicting the need for liver transplantation .Arterial blood lactate greater than 3.5 mmol/L 4 hours after presentation to the hospital has been shown to have a sensitivity of 67%, a specificity of 95%, a positive likelihood ratio of 13%, and a negative likelihood ratio of 35% for survival in acetaminophen-induced fulminant hepatic failure .
Advances in Artificial and Bioartificial Support Systems
Short-term extracorporeal support for patients with fulminant hepatic failure may ultimately serve to improve overall survival and provide support as a bridge to liver transplantation, but remains experimental. A metaanalysis of artificial and bioartificial support systems for fulminant hepatic failure examined a total of 8 randomized controlled trials, involving 139 patients, and found no improvement in mortality compared with standard supportive care (relative risk, 0.95; 95% confidence interval, 0.71-1.29) .In addition, the interventions were not found to be useful as a bridge to liver transplantation (relative risk, 0.60; 95% confidence interval, 0.29-1.23). The support systems appeared to have an increased risk of bleeding associated with their use. A future option is hepatocyte transplantation. In one series, three of six patients with fulminant hepatic failure survived between 14 and 52 days after transplantation of 10^sup 10^ human hepatocytes .To date, no randomized, controlled studies have examined this therapeutic option.
Recommendations
Once the diagnosis is made, all necessary supportive measures should be employed in an ICU setting. Neurologic evaluation and glucose monitoring should be performed frequently. Coagulopathy should be corrected when there is overt bleeding or an invasive procedure is planned. An emergent head computed tomography scan should be performed if there is a change in mental status or signs of increased intracranial pressure. Intracranial pressure monitoring is recommended to maintain an adequate cerebral perfusion pressure of greater than 60 mm Hg. Currently, liver transplantation offers the best long-term survival in patients likely to die of fulminant hepatic failure.
Bharesh Dedhia
How to Cope with Critical Illnesses in Family by Bharesh Dedhia
Bharesh Dedhia
To be strong for your loved one in the ICU, you must first take care of yourself.Self-careAs a family member or a significant person in a patient's life, you may experience feelings of helplessness or loss of control when a loved one is in the intensive care unit. This brochure is designed to provide strategies to help you cope with visiting someone who has a prolonged critical illness. It is difficult to wait without action, but you can do something: You can first take care of yourself.You are as important to the healing process as the physicians, nurses, medications, and treatments. You have been a part of the patient's life journey long before, and will be long after, this hospitalization.We now realize what a strong influence positive reinforcement and encouragement from close friends and family have on the healing process. We are learning more and more about the benefits of family involvement in the delivery of patient care. Because of this, your well being is important to your loved one and us. The following recommendations are designed to provide you with strategies that will help you take care of yourself during this difficult time.Take care of yourselfProper food and sleep will enhance your ability to listen and understand the significant information you will be given. Stressful situations in addition to staying awake all night, every night, will eventually wear on you, and can make you prone to illness. Try to eat healthy foods regularly. Whenever possible, get up and walk around. Exercise is very important to maintaining emotional health. Do not feel you have to be available every moment. A trained medical team is caring for your loved one. The patients are closely monitored even though there are not care providers directly in the patient's room at all times. Remember your loved one needs all the strength you can give.Gathering supportAn important measure in taking care of yourself is to gather support from family and friends. If other friends or family come to visit, take that opportunity for a little time to refresh yourself. Structure time away from the hospital by asking a friend or family member to take over for a few hours. Make a rotational system if there are many people available to help. Remember that the time in the ICU may be the beginning of a longer recovery where your strength will be needed as well. If family members from out of town offer to visit, encourage and welcome their support. The nurses and doctors take breaks during their shift because the continual light and noise are draining. You should be taking regular breaks from the constant sensory input as well. When someone asks, "What can we do for you, we're here to help," give yourself permission to ask for help. A critical illness in the family is truly the time to muster support from those who care.Identify a family spokespersonThe role of this person will be to contact all the friends and relatives who need to be reached each day to provide them with an update on the patient's condition. We know that access to information is one of the most significant needs of families of ICU patients. It is recommended that the spokesperson not have the primary relationship to the patient (spouse, parent of a child, significant other). Having someone else serve as family spokesperson relieves him or her of the responsibility to follow through with this most important task. Having a family spokesperson also eliminates frequent calls into the ICU which can pull the nurse away from the patient's bedside.Support at homeAs you spend many hours in the intensive care unit supporting your loved one, matters may go unattended at home. Make sure you delegate someone to pick up your newspaper and mail. If someone offers to cook or clean for you, take them up on it! Ask someone you trust to make sure all your bills are being paid. And most importantly, make sure your child care is in order.Prepare yourself dailyPrepare yourself for setbacks. Most patients in the ICU are on a roller coaster ride. Some days are good and some are bad. Concentrate on the steps taken forward and view the steps backward as hurdles that can be overcome. Try not to become discouraged. Like the patient, it is also normal for family and friends to have both good and bad days.Purchase a notebookDivide it into 3 separate areas. On the first page of the notebook place the name of the intensivist, the physicians, the social worker, and any other care provider that is involved with the care of your loved one. On the second page place all the phone numbers of the various people you would like to contact each day. Don't forget to include work and school colleagues.In the second section write down your questions. Anytime you think of something you are concerned about, even if you don't think it is important, write it down. As you continue through your process of waiting, you may forget what you were told, or how you were supposed to follow up on the information you received. You may need to have information repeated several times before you understand it. This is normal. Don't be afraid to ask for clarification.In the third section start a journal. Some family members have found keeping a daily journal of events, in and out of the hospital, to be very healing. It can also provide you with encouragement as you see small improvements over time.Be positive!Keep your faith and your hope strong, making sure that everybody is encouraging and hopeful while with your loved one. If your loved one is not alert, always begin your visit with your name. "Hi, it's _____." Talk to your loved one and tell them what is going on. Read cards that have been sent. All these things can help with their recovery.Bharesh Dedhia
To be strong for your loved one in the ICU, you must first take care of yourself.Self-careAs a family member or a significant person in a patient's life, you may experience feelings of helplessness or loss of control when a loved one is in the intensive care unit. This brochure is designed to provide strategies to help you cope with visiting someone who has a prolonged critical illness. It is difficult to wait without action, but you can do something: You can first take care of yourself.You are as important to the healing process as the physicians, nurses, medications, and treatments. You have been a part of the patient's life journey long before, and will be long after, this hospitalization.We now realize what a strong influence positive reinforcement and encouragement from close friends and family have on the healing process. We are learning more and more about the benefits of family involvement in the delivery of patient care. Because of this, your well being is important to your loved one and us. The following recommendations are designed to provide you with strategies that will help you take care of yourself during this difficult time.Take care of yourselfProper food and sleep will enhance your ability to listen and understand the significant information you will be given. Stressful situations in addition to staying awake all night, every night, will eventually wear on you, and can make you prone to illness. Try to eat healthy foods regularly. Whenever possible, get up and walk around. Exercise is very important to maintaining emotional health. Do not feel you have to be available every moment. A trained medical team is caring for your loved one. The patients are closely monitored even though there are not care providers directly in the patient's room at all times. Remember your loved one needs all the strength you can give.Gathering supportAn important measure in taking care of yourself is to gather support from family and friends. If other friends or family come to visit, take that opportunity for a little time to refresh yourself. Structure time away from the hospital by asking a friend or family member to take over for a few hours. Make a rotational system if there are many people available to help. Remember that the time in the ICU may be the beginning of a longer recovery where your strength will be needed as well. If family members from out of town offer to visit, encourage and welcome their support. The nurses and doctors take breaks during their shift because the continual light and noise are draining. You should be taking regular breaks from the constant sensory input as well. When someone asks, "What can we do for you, we're here to help," give yourself permission to ask for help. A critical illness in the family is truly the time to muster support from those who care.Identify a family spokespersonThe role of this person will be to contact all the friends and relatives who need to be reached each day to provide them with an update on the patient's condition. We know that access to information is one of the most significant needs of families of ICU patients. It is recommended that the spokesperson not have the primary relationship to the patient (spouse, parent of a child, significant other). Having someone else serve as family spokesperson relieves him or her of the responsibility to follow through with this most important task. Having a family spokesperson also eliminates frequent calls into the ICU which can pull the nurse away from the patient's bedside.Support at homeAs you spend many hours in the intensive care unit supporting your loved one, matters may go unattended at home. Make sure you delegate someone to pick up your newspaper and mail. If someone offers to cook or clean for you, take them up on it! Ask someone you trust to make sure all your bills are being paid. And most importantly, make sure your child care is in order.Prepare yourself dailyPrepare yourself for setbacks. Most patients in the ICU are on a roller coaster ride. Some days are good and some are bad. Concentrate on the steps taken forward and view the steps backward as hurdles that can be overcome. Try not to become discouraged. Like the patient, it is also normal for family and friends to have both good and bad days.Purchase a notebookDivide it into 3 separate areas. On the first page of the notebook place the name of the intensivist, the physicians, the social worker, and any other care provider that is involved with the care of your loved one. On the second page place all the phone numbers of the various people you would like to contact each day. Don't forget to include work and school colleagues.In the second section write down your questions. Anytime you think of something you are concerned about, even if you don't think it is important, write it down. As you continue through your process of waiting, you may forget what you were told, or how you were supposed to follow up on the information you received. You may need to have information repeated several times before you understand it. This is normal. Don't be afraid to ask for clarification.In the third section start a journal. Some family members have found keeping a daily journal of events, in and out of the hospital, to be very healing. It can also provide you with encouragement as you see small improvements over time.Be positive!Keep your faith and your hope strong, making sure that everybody is encouraging and hopeful while with your loved one. If your loved one is not alert, always begin your visit with your name. "Hi, it's _____." Talk to your loved one and tell them what is going on. Read cards that have been sent. All these things can help with their recovery.Bharesh Dedhia
How to Cope with Critical Illnesses in Family by Bharesh Dedhia
Bharesh DedhiaTo be strong for your loved one in the ICU, you must first take care of yourself.Self-careAs a family member or a significant person in a patient's life, you may experience feelings of helplessness or loss of control when a loved one is in the intensive care unit. This brochure is designed to provide strategies to help you cope with visiting someone who has a prolonged critical illness. It is difficult to wait without action, but you can do something: You can first take care of yourself.You are as important to the healing process as the physicians, nurses, medications, and treatments. You have been a part of the patient's life journey long before, and will be long after, this hospitalization.We now realize what a strong influence positive reinforcement and encouragement from close friends and family have on the healing process. We are learning more and more about the benefits of family involvement in the delivery of patient care. Because of this, your well being is important to your loved one and us. The following recommendations are designed to provide you with strategies that will help you take care of yourself during this difficult time.Take care of yourselfProper food and sleep will enhance your ability to listen and understand the significant information you will be given. Stressful situations in addition to staying awake all night, every night, will eventually wear on you, and can make you prone to illness. Try to eat healthy foods regularly. Whenever possible, get up and walk around. Exercise is very important to maintaining emotional health. Do not feel you have to be available every moment. A trained medical team is caring for your loved one. The patients are closely monitored even though there are not care providers directly in the patient's room at all times. Remember your loved one needs all the strength you can give.Gathering supportAn important measure in taking care of yourself is to gather support from family and friends. If other friends or family come to visit, take that opportunity for a little time to refresh yourself. Structure time away from the hospital by asking a friend or family member to take over for a few hours. Make a rotational system if there are many people available to help. Remember that the time in the ICU may be the beginning of a longer recovery where your strength will be needed as well. If family members from out of town offer to visit, encourage and welcome their support. The nurses and doctors take breaks during their shift because the continual light and noise are draining. You should be taking regular breaks from the constant sensory input as well. When someone asks, "What can we do for you, we're here to help," give yourself permission to ask for help. A critical illness in the family is truly the time to muster support from those who care.Identify a family spokespersonThe role of this person will be to contact all the friends and relatives who need to be reached each day to provide them with an update on the patient's condition. We know that access to information is one of the most significant needs of families of ICU patients. It is recommended that the spokesperson not have the primary relationship to the patient (spouse, parent of a child, significant other). Having someone else serve as family spokesperson relieves him or her of the responsibility to follow through with this most important task. Having a family spokesperson also eliminates frequent calls into the ICU which can pull the nurse away from the patient's bedside.Support at homeAs you spend many hours in the intensive care unit supporting your loved one, matters may go unattended at home. Make sure you delegate someone to pick up your newspaper and mail. If someone offers to cook or clean for you, take them up on it! Ask someone you trust to make sure all your bills are being paid. And most importantly, make sure your child care is in order.Prepare yourself dailyPrepare yourself for setbacks. Most patients in the ICU are on a roller coaster ride. Some days are good and some are bad. Concentrate on the steps taken forward and view the steps backward as hurdles that can be overcome. Try not to become discouraged. Like the patient, it is also normal for family and friends to have both good and bad days.Purchase a notebookDivide it into 3 separate areas. On the first page of the notebook place the name of the intensivist, the physicians, the social worker, and any other care provider that is involved with the care of your loved one. On the second page place all the phone numbers of the various people you would like to contact each day. Don't forget to include work and school colleagues.In the second section write down your questions. Anytime you think of something you are concerned about, even if you don't think it is important, write it down. As you continue through your process of waiting, you may forget what you were told, or how you were supposed to follow up on the information you received. You may need to have information repeated several times before you understand it. This is normal. Don't be afraid to ask for clarification.In the third section start a journal. Some family members have found keeping a daily journal of events, in and out of the hospital, to be very healing. It can also provide you with encouragement as you see small improvements over time.Be positive!Keep your faith and your hope strong, making sure that everybody is encouraging and hopeful while with your loved one. If your loved one is not alert, always begin your visit with your name. "Hi, it's _____." Talk to your loved one and tell them what is going on. Read cards that have been sent. All these things can help with their recovery.Bharesh Dedhia
Alternate modalities for nutrition by Bharesh Dedhia
Bharesh Dedhia
Glutamine has been the focus of much study because it may be important in the maintenance of gut and immunological integrity during critical illness. It is the most abundant free amino acid in the circulation and is a primary fuel for rapidly dividing cells such as enterocytes and immunocytes .It is also involved in the inter-organ transport of nitrogen. Evidence from animal studies has indicated that glutamine may be an essential amino acid during critical illness and that parenteral and enteral glutamine-supplemented nutrition may prevent bacterial translocation. The data in humans are less compelling .Glutamine is rather insoluble and thus is difficult to administer. Some success has been achieved infusing it as the L-amino acid, glutamine-dipeptides or alanyl-glutamate. Initial reports indicate that in some catabolic patients glutamine-containing nutrition may improve gut structure and function, exert an anabolic effect and reduce morbidity, hospital costs, infection rates and duration of hospital stay. More studies are needed to ascertain whether glutamine administration improves outcome .Access for enteral nutrition is a problematic issue due to the problems of securing a reliable route. Placement of the tip of the tube into the jejunum is considered ideal so as to avoid the often present gastric ileus and possibly prevent aspiration. There has been some disagreement as to whether it is mandatory to place the tube into the jejunum. The ideal route is a jejunostomy catheter placed during laparotomy, because feeding may begin within hours of surgery. Complication rates are comparatively low (1.5%) and most commonly involve catheter occlusion or dislodgment. Very rarely bowel necrosis or intra-abdominal leaks may occur .Alternatively, a nasoenteric tube can be passed during surgery and manually manipulated into the jejunum. In patients without surgical placement, nasoenteric tubes may be placed. It is often difficult to pass such tubes from the stomach into the jejunum. Right lateral decubitus positioning and prokinetic drugs may be tried, but often placement must be performed under radiological or endoscopic guidance.
Bharesh Dedhia
Glutamine has been the focus of much study because it may be important in the maintenance of gut and immunological integrity during critical illness. It is the most abundant free amino acid in the circulation and is a primary fuel for rapidly dividing cells such as enterocytes and immunocytes .It is also involved in the inter-organ transport of nitrogen. Evidence from animal studies has indicated that glutamine may be an essential amino acid during critical illness and that parenteral and enteral glutamine-supplemented nutrition may prevent bacterial translocation. The data in humans are less compelling .Glutamine is rather insoluble and thus is difficult to administer. Some success has been achieved infusing it as the L-amino acid, glutamine-dipeptides or alanyl-glutamate. Initial reports indicate that in some catabolic patients glutamine-containing nutrition may improve gut structure and function, exert an anabolic effect and reduce morbidity, hospital costs, infection rates and duration of hospital stay. More studies are needed to ascertain whether glutamine administration improves outcome .Access for enteral nutrition is a problematic issue due to the problems of securing a reliable route. Placement of the tip of the tube into the jejunum is considered ideal so as to avoid the often present gastric ileus and possibly prevent aspiration. There has been some disagreement as to whether it is mandatory to place the tube into the jejunum. The ideal route is a jejunostomy catheter placed during laparotomy, because feeding may begin within hours of surgery. Complication rates are comparatively low (1.5%) and most commonly involve catheter occlusion or dislodgment. Very rarely bowel necrosis or intra-abdominal leaks may occur .Alternatively, a nasoenteric tube can be passed during surgery and manually manipulated into the jejunum. In patients without surgical placement, nasoenteric tubes may be placed. It is often difficult to pass such tubes from the stomach into the jejunum. Right lateral decubitus positioning and prokinetic drugs may be tried, but often placement must be performed under radiological or endoscopic guidance.
Bharesh Dedhia
Disease Specific Feeding by Bharesh Dedhia
Bharesh Dedhia
Immune-enhancing
One recent advance in enteral nutrition has been the use of so-called "immune-enhancing" formulas that include arginine, glutamine, nucleotides, and/or omega-3 fatty acids (fish oil) in septic and catabolic patients. In a multicenter trial, trauma patients receiving such a formula experienced significantly fewer intra-abdominal abscesses and less multiple organ failure.
Pulmonary
Pulmonary formulas are designed to be high in fat (50%) and low in carbohydrates to reduce CO2 production, thereby reducing ventilatory demand. In preclinical studies, a tailored pulmonary formula reduced pulmonary neutrophil accumulation and inflammatory cytokines and improved cardiopulmonary hemodynamics and gas exchange. This disease-specific pulmonary formulation contains eicosapentaenoic acid and -linolenic acid (which modify production of proinflammatory cytokines) and antioxidants (vitamin E, vitamin C, and beta-carotene), and is a calorically dense formula, suitable in particular for fluid-restricted patients with ARDS.
Hepatic
Hepatic enteral formulas contain relative large amounts of the BCAAs valine, leucine, and isoleucine, with low quantities of aromatic amino acids. These products are tailored for patients with hepatic encephalopathy.The rationale is that infusion of BCAA corrects the imbalance between aromatic amino acids and BCAAs in plasma and the CNS that might contribute to the mental disturbances that are common. The use of BCAA-enriched formulas for short periods may be beneficial because they improve nitrogen balance and lessen encephalopathy, but their use for longer periods becomes expensive and may limit protein synthesis, resulting in an inadequate nitrogen balance.
Renal
Specific renal formulas are usually low in protein or contain variable proportions of BCAA. The solutions are usually calorically dense and contain up to 2 kcal/mL. To achieve this density, some formulas may contain significant amounts of fat, the ingestion of which may result in bloating and delayed gastric emptying. Potassium, phosphorus, and magnesium are present in substantially lower amounts than is the case for typical enteral feeds. Renal patients are also at increased risk of certain micronutrient toxicities. However, it is important to feed patients adequately to avoid body cell mass catabolism and malnutrition. For critically ill patients, it is best to use dialysis to clear nitrogen and fluid and to feed them an adequate protein diet than to underfeed protein.Bharesh Dedhia
Immune-enhancing
One recent advance in enteral nutrition has been the use of so-called "immune-enhancing" formulas that include arginine, glutamine, nucleotides, and/or omega-3 fatty acids (fish oil) in septic and catabolic patients. In a multicenter trial, trauma patients receiving such a formula experienced significantly fewer intra-abdominal abscesses and less multiple organ failure.
Pulmonary
Pulmonary formulas are designed to be high in fat (50%) and low in carbohydrates to reduce CO2 production, thereby reducing ventilatory demand. In preclinical studies, a tailored pulmonary formula reduced pulmonary neutrophil accumulation and inflammatory cytokines and improved cardiopulmonary hemodynamics and gas exchange. This disease-specific pulmonary formulation contains eicosapentaenoic acid and -linolenic acid (which modify production of proinflammatory cytokines) and antioxidants (vitamin E, vitamin C, and beta-carotene), and is a calorically dense formula, suitable in particular for fluid-restricted patients with ARDS.
Hepatic
Hepatic enteral formulas contain relative large amounts of the BCAAs valine, leucine, and isoleucine, with low quantities of aromatic amino acids. These products are tailored for patients with hepatic encephalopathy.The rationale is that infusion of BCAA corrects the imbalance between aromatic amino acids and BCAAs in plasma and the CNS that might contribute to the mental disturbances that are common. The use of BCAA-enriched formulas for short periods may be beneficial because they improve nitrogen balance and lessen encephalopathy, but their use for longer periods becomes expensive and may limit protein synthesis, resulting in an inadequate nitrogen balance.
Renal
Specific renal formulas are usually low in protein or contain variable proportions of BCAA. The solutions are usually calorically dense and contain up to 2 kcal/mL. To achieve this density, some formulas may contain significant amounts of fat, the ingestion of which may result in bloating and delayed gastric emptying. Potassium, phosphorus, and magnesium are present in substantially lower amounts than is the case for typical enteral feeds. Renal patients are also at increased risk of certain micronutrient toxicities. However, it is important to feed patients adequately to avoid body cell mass catabolism and malnutrition. For critically ill patients, it is best to use dialysis to clear nitrogen and fluid and to feed them an adequate protein diet than to underfeed protein.Bharesh Dedhia
Gut Feeding in Critical Care
Bharesh Dedhia
Gut Feeding in Critical CareIntragastric feeding requires adequate gastric motility and emptying; a residual of > 150 mL is a relative contraindication to gastric feeding as the risk of aspiration is high. Nutrition support with TPN or small-bowel feeding is then appropriate. Postpyloric enteral feeding is often effective even in the presence of gastric atony and/or colonic ileus. For effective small-bowel feeding, simultaneous nasogastric decompression may be required. The presence of bowel sounds and the passage of flatus or stool are not necessary to initiate postpyloric enteral feeding. Secretory diarrhea may occur and is not an absolute indication to discontinue enteral feedings unless output exceeds 1,000 mL/d. Output in this range requires an evaluation.Enteral feeding is usually started with an elemental formula with reduced fat content at low rates until tolerance is determined. Rates may be advanced toward the goal every 8 h, as tolerated, as long as the gastric residual is low, and abdominal distension and pain are absent. Multiple vitamins need to be ordered separately. Caloric requirements are calculated as for TPN.BhareshDedhia
Gut Feeding in Critical CareIntragastric feeding requires adequate gastric motility and emptying; a residual of > 150 mL is a relative contraindication to gastric feeding as the risk of aspiration is high. Nutrition support with TPN or small-bowel feeding is then appropriate. Postpyloric enteral feeding is often effective even in the presence of gastric atony and/or colonic ileus. For effective small-bowel feeding, simultaneous nasogastric decompression may be required. The presence of bowel sounds and the passage of flatus or stool are not necessary to initiate postpyloric enteral feeding. Secretory diarrhea may occur and is not an absolute indication to discontinue enteral feedings unless output exceeds 1,000 mL/d. Output in this range requires an evaluation.Enteral feeding is usually started with an elemental formula with reduced fat content at low rates until tolerance is determined. Rates may be advanced toward the goal every 8 h, as tolerated, as long as the gastric residual is low, and abdominal distension and pain are absent. Multiple vitamins need to be ordered separately. Caloric requirements are calculated as for TPN.BhareshDedhia
TPN in Critical Care by Bharesh Dedhia
TPN in Critical Care - Bharesh DedhiaIn general, the enteral route is preferred over the parenteral route, as the former is more physiologic, is less likely to be associated with biliary stasis and hyperglycemia, and is significantly less expensive.9 Many studies have purported to show that total parenteral nutrition (TPN) is associated with higher infection rates than is enteral feeding, although this has not been confirmed when equivalent calories have been administered by each route and when overfeeding with TPN is avoided.Contraindications to enteral feeding include diffuse peritonitis, intestinal obstruction, intractable vomiting, paralytic ileus, and severe diarrhea. Hypotension with hemodynamic instability is associated with reduced intestinal blood flow, and low tolerance to enteral feeding is the rule.TPN plays an important role in patients in whom the gut cannot be used. Administration of 25 kcal/kg of usual body weight is adequate for most patients with normal BMI. In most patients this goal approximates the one calculated from the Harris Benedict equation. With BMI <> 100 mg/dL might be an indication to decrease nitrogen intake, although this is not well validated in the acute illness setting. A more usual issue in feeding the patient with acute renal failure is that volume restrictions limit the quantity of feeding. In persons with chronic renal insufficiency, 0.8 g/kg/d of protein is sufficient. Another possible indication for limiting protein consumption in TPN occurs in persons in whom hepatic encephalopathy is a major clinical problem. Reducing the amino acid load or using a high quantity of branched-chain amino acids (BCAAs) have been shown to improve mental status.The lipid component of TPN consists of omega-6-polyunsaturated fatty acids that may be administered separately from the dextrose/protein or as part of a three-in-one solution. Theoretical concerns with overfeeding of lipids include injury to the reticuloendothelial system, which might lead to immunosuppression and can negate the beneficial effect of nutrition support. However, limiting fat calories to 30% of total calories is unlikely to lead to this complication, especially when the fat is infused slowly as with the three-in-one solution. Triglyceride levels > 400 mg/dL are a relative contraindication to adding lipids.Carbohydrates should constitute the remainder of the total calories at between 3 and 5 g/kg/d,8 however, the specific amount should be adjusted appropriately to maintain a blood glucose level <> 220 mg/dL) has been shown to increase the risk of nosocomial infection to a degree that nullifies the benefits of nutritional repletion.16 Severe stress (eg, postoperative patients) is accompanied by rising plasma levels of the counterregulatory hormones glucagon, epinephrine, and cortisol, and thus, postoperative patients are most at risk from TPN-induced hyperglycemia.Fluid restriction is often vital in cardiac, pulmonary, postoperative, and renal patients in the ICU. For such patients, TPN can be restricted to 1 L. Maximally concentrating nutrients allows the provision of 1,000 kcal and 70 g of protein per liter, which is often a substantial percentage of the weight-based feeding goal. Vitamins and trace elements are usually administered as components of the TPN. In addition, a number of medications, such as histamine-2 receptor antagonists and metaclopramide, can be mixed in with the TPN solution.Bharesh Dedhia
NAC in Acute liver disease by Bharesh Dedhia
Bharesh dedhia
There is no doubt that N-acetylcysteine has saved countless lives in the management of paracetmol haepatotoxicty. In the first instance, this is due to the N-acetylcysteine acting replenishing stores of glutathione, which prevents hepatic damage by binding to a toxic metabolite of paracetamol. However, the effects of N-acetylcysteine seem to go beyond this, as there is evidence that continued infusion of N-acetylcysteine has beneficial effects in patients with established paracetamol induced hepatic damage, long after paracetamol has been cleared. Thus, the next logical step is to ask if N-acetylcysteine has a role in acute liver failure not caused by paracetamol. The papers discussed above have started the ball rolling in answering this, through several different approaches. Experimental evidence in rats would suggest there is a benefit, and two out three investigations show a beneficial effect of N-acetylcysteine on various physiological parameters in humans. These papers are however beset by the weaknesses described above. Perhaps more promising are the actual case reports of N-acetylcysteine playing a role in recovery from acute liver failure .These are, however, just isolated reports. One must remember that there may have been many times when N-acetylcysteine has been used but has failed to provide any benefit in the clinical setting. Such cases may not have been reported, thus creating a skewed view in the literature of only successful cases.
However it may be useful of try NAC in acute liver disease, as generally it is well tolerated. A large RCT would be helpful to settle the issue once and for all. Bharesh Dedhia
There is no doubt that N-acetylcysteine has saved countless lives in the management of paracetmol haepatotoxicty. In the first instance, this is due to the N-acetylcysteine acting replenishing stores of glutathione, which prevents hepatic damage by binding to a toxic metabolite of paracetamol. However, the effects of N-acetylcysteine seem to go beyond this, as there is evidence that continued infusion of N-acetylcysteine has beneficial effects in patients with established paracetamol induced hepatic damage, long after paracetamol has been cleared. Thus, the next logical step is to ask if N-acetylcysteine has a role in acute liver failure not caused by paracetamol. The papers discussed above have started the ball rolling in answering this, through several different approaches. Experimental evidence in rats would suggest there is a benefit, and two out three investigations show a beneficial effect of N-acetylcysteine on various physiological parameters in humans. These papers are however beset by the weaknesses described above. Perhaps more promising are the actual case reports of N-acetylcysteine playing a role in recovery from acute liver failure .These are, however, just isolated reports. One must remember that there may have been many times when N-acetylcysteine has been used but has failed to provide any benefit in the clinical setting. Such cases may not have been reported, thus creating a skewed view in the literature of only successful cases.
However it may be useful of try NAC in acute liver disease, as generally it is well tolerated. A large RCT would be helpful to settle the issue once and for all. Bharesh Dedhia
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