Acute liver failure medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{Acute liver failure}}
{{Acute liver failure}}
{{CMG}} {{AE}} {{ADI}}
{{CMG}} {{AE}} {{ADI}} {{HS}}
 
 
==Overview==
==Overview==
The management of acute liver failure involves resuscitation of the patient with adequate nutrition and optimization of [[fluid balance]], monitoring and treating the complications and providing nutritional support. The patient should be treated in an appropriate setting preferably a center with liver transplantation facility. Infections and sepsis are common occurrences of [[fulminant liver failure]]. The high standards of infection control should be practiced to minimize the [[Nosocomial infection|nosocomial sepsis]]. The diagnosis of hepatic injury in [[Hepatic failure|hyperacute cases]] can be a challenge as jaundice can be minimal during that period and confusion or agitation may be the dominant findings. In acute liver failure, the sedative medications should be used with caution as they may mask the worsening [[encephalopathy]] and the hepatic clearance may be decreased which can aggravate the sedative effect. However, the short-acting [[benzodiazepines]] in low dose can be used during agitation. In [[acute liver failure]] patients, [[opioids]] are avoided as they decrease the [[seizure]] threshold. [[H2 receptor antagonist|H2 receptor blockers]] and [[proton pump inhibitors]] are indicated to prevent and treat [[Stress ulcer|stress gastropathy]]. In stage 3 and 4 [[encephalopathy]], [[intubation]] and [[mechanical ventilation]] are indicated. [[Acetylcysteine]] is used for [[acetaminophen]] poisoning for up to 72 hours after ingestion. It can dramatically improve the outcome if administered within eight hours of acetaminophen ingestion. The patients with acute liver failure may not have a clear history of acetaminophen intake. Therefore, the threshold for administering acetylcysteine should be low and can also be administered in an acute liver failure of unknown etiology.  Every effort should be made to seek out the specific cause of acute liver failure since specific treatments are available for some causes of acute liver failure. However, inappropriately prolonged investigations may make surgery impossible because of progression of [[sepsis]] and [[Multiorgan failure|multiorgan failure.]]


==Medical Therapy==
==Medical Therapy==
* The management of acute liver failure involves taking care of the patient in an appropriate setting, preferably a center with liver transplantation facility, monitoring and treating the complications and providing nutritional support.<ref name="pmid2933761">{{cite journal |vauthors=Khadzhidekova VB, Benova DK, Ivanov BA, Mileva MS, Kolev MI |title=[Mutagenic effect of the cytostatic drug thaliblastine on rat bone marrow cells when administered alone and in combination with radiation] |language=Russian |journal=Radiobiologiia |volume=25 |issue=5 |pages=656–60 |year=1985 |pmid=2933761 |doi= |url=}}</ref>
* The management of acute liver failure involves taking care of the patient in an appropriate setting, preferably a center with liver transplantation facility, monitoring and treating the complications and providing nutritional support.<ref name="pmid2933761">{{cite journal |vauthors=Khadzhidekova VB, Benova DK, Ivanov BA, Mileva MS, Kolev MI |title=[Mutagenic effect of the cytostatic drug thaliblastine on rat bone marrow cells when administered alone and in combination with radiation] |language=Russian |journal=Radiobiologiia |volume=25 |issue=5 |pages=656–60 |year=1985 |pmid=2933761 |doi= |url=}}</ref><ref name="pmid26325537">{{cite journal| author=Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC et al.| title=High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial. | journal=J Hepatol | year= 2016 | volume= 64 | issue= 1 | pages= 69-78 | pmid=26325537 | doi=10.1016/j.jhep.2015.08.018 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26325537  }} </ref><ref name="pmid15082970">{{cite journal |vauthors=Demetriou AA, Brown RS, Busuttil RW, Fair J, McGuire BM, Rosenthal P, Am Esch JS, Lerut J, Nyberg SL, Salizzoni M, Fagan EA, de Hemptinne B, Broelsch CE, Muraca M, Salmeron JM, Rabkin JM, Metselaar HJ, Pratt D, De La Mata M, McChesney LP, Everson GT, Lavin PT, Stevens AC, Pitkin Z, Solomon BA |title=Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure |journal=Ann. Surg. |volume=239 |issue=5 |pages=660–7; discussion 667–70 |year=2004 |pmid=15082970 |pmc=1356274 |doi= |url=}}</ref><ref name="pmid24126646">{{cite journal| author=Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B et al.| title=Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial. | journal=Ann Intern Med | year= 2013 | volume= 159 | issue= 8 | pages= 522-31 | pmid=24126646 | doi=10.7326/0003-4819-159-8-201310150-00005 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24126646  }} </ref><ref name="pmid22447262">{{cite journal| author=Tritto G, Davies NA, Jalan R| title=Liver replacement therapy. | journal=Semin Respir Crit Care Med | year= 2012 | volume= 33 | issue= 1 | pages= 70-9 | pmid=22447262 | doi=10.1055/s-0032-1301736 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22447262  }} </ref><ref name="pmid21462172">{{cite journal| author=Stutchfield BM, Simpson K, Wigmore SJ| title=Systematic review and meta-analysis of survival following extracorporeal liver support. | journal=Br J Surg | year= 2011 | volume= 98 | issue= 5 | pages= 623-31 | pmid=21462172 | doi=10.1002/bjs.7418 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21462172  }} </ref>
====General measures====
====General measures====
* The goal is to resuscitate the patient with adequate nutrition and optimization of [[fluid balance]].  
* The goal is to resuscitate the patient with adequate nutrition and optimization of [[fluid balance]].  
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* Infections and [[sepsis]] are common occurrences with [[fulminant liver failure]]. The high standards of infection control should be practiced to minimize the nosocomial sepsis.
* Infections and [[sepsis]] are common occurrences with [[fulminant liver failure]]. The high standards of infection control should be practiced to minimize the nosocomial sepsis.
* [[H2 receptor blocker]]s and [[proton pump inhibitors]] are indicated to prevent and treat [[stress gastropathy]].
* [[H2 receptor blocker]]s and [[proton pump inhibitors]] are indicated to prevent and treat [[stress gastropathy]].
* Early transfer to a liver transplantation center should be considered based on a patient's clinical status.
* Early transfer to a [[liver transplantation]] center should be considered based on a patient's clinical status.
* The diagnosis of hepatic injury in hyperacute cases can be a challenge as jaundice can be minimal during that period and confusion or agitation may be the dominant findings.
* The diagnosis of [[Hepatic|hepatic injury]] in [[Hepatic failure|hyperacute]] cases can be a challenge as [[jaundice]] can be minimal during that period and confusion or agitation may be the dominant findings.
* In acute liver failure, the sedative medications should be used with caution as they may mask the worsening encephalopathy and the hepatic clearance may be decreased which can aggravate the sedative effect. However, the short-acting benzodiazepines in low dose can be used during agitation.
* In [[acute liver failure]], the sedative medications should be used with caution as they may mask the worsening [[encephalopathy]] and the hepatic clearance may be decreased which can aggravate the sedative effect. However, the short-acting [[benzodiazepines]] in low dose can be used during agitation.
* In acute liver failure patients opioids are avoided as they decrease the seizure threshold.
* In [[acute liver failure]] patients [[opioids]] are avoided as they decrease the [[Seizure|seizure threshold.]]
* Every effort should be made to sought out the specific cause of acute liver failure since specific treatments are available for some causes of acute liver failure. However, inappropriately prolonged investigations may make surgery impossible because of progression of sepsis and multiorgan failure.
* Every effort should be made to seek out the specific cause of acute liver failure since specific treatments are available for some causes of acute liver failure. However, inappropriately prolonged investigations may make surgery impossible because of progression of [[sepsis]] and [[multiorgan failure]].


==Management of complications==
==Management of complications==
===Encephalopathy===
===Encephalopathy===
* The goal of management is to limit the severity of encephalopathy and reduce the risk of cerebral edema.
* The goal of management is to limit the severity of [[encephalopathy]] and reduce the risk of [[Cerebral edema|cerebral edema.]]
* Grade I can be managed on the floors with adequate skilled nursing staff in a calm atmosphere, as it helps in reducing agitation.
* Grade I can be managed on the floors with adequate skilled nursing staff in a calm atmosphere, as it helps in reducing agitation.
* Grade II encephalopathy has must be managed in ICU setting.
* Grade II encephalopathy has must be managed in ICU setting.
* For grades III/IV encephalopathy, intubation, and mechanical ventilation are required for management.
* For grades III/IV encephalopathy, intubation, and mechanical ventilation are required for management.
* Monitoring and management of hemodynamic and renal parameters as well as [[glucose]], [[electrolytes]] and acid/base status is also important.
* Monitoring and management of [[Hemodynamics|hemodynamic]] and [[renal]] parameters as well as [[glucose]], [[electrolytes]] and [[acid-base]] status is also important.


===Increased Intracranial Pressure===
===Increased Intracranial Pressure===
* Monitoring for increased [[intracranial pressure]] in severe encephalopathy, and impending cerebral edema should be done with extradural sensors.
* Monitoring for increased [[intracranial pressure]] in severe encephalopathy, and impending [[cerebral edema]] should be done with [[Dura|extradural]] sensors.
* The goal should be to maintain the intracranial pressure below 20 mm Hg, and the cerebral perfusion pressure above 70 mm Hg.
* The goal should be to maintain the intracranial pressure below 20 mm Hg, and the [[cerebral perfusion pressure]] above 70 mm Hg.
* [[Mannitol]], 0.5 g/kg, or 100–200 mL of a 20% solution by intravenous infusion over 10 minutes for is indicated for reducing sustained cerebral edema.
* [[Mannitol]], 0.5 g/kg, or 100–200 mL of a 20% solution by intravenous infusion over 10 minutes is indicated for reducing sustained [[cerebral edema]].
* [[Hypothermia]] (32–34 °C) may reduce intracranial pressure in refractory cases as it affects multiple processes involved in the development of cerebral edema such as slowing of body metabolism, it lowers systemic production, cerebral uptake and metabolism of ammonia as well as hemodynamic stabilizing effects and reducing cerebral blood flow.
* [[Hypothermia]] (32–34 °C) may reduce [[intracranial pressure]] in refractory cases as it affects multiple processes involved in the development of cerebral edema such as slowing of body metabolism, it lowers systemic production, cerebral uptake and metabolism of ammonia as well as [[Hemodynamics|hemodynamic]] stabilizing effects and reducing [[cerebral blood flow]].
* Short-acting [[barbiturate]]s, [[propofol]], or IV [[indomethacin]] can be used for refractory intracranial hypertension.
* Short-acting [[barbiturate]]s, [[propofol]], or IV [[indomethacin]] can be used for [[Intracranial hypertension|refractory intracranial hypertension]].


===Infections===
===Infections===
* The use of antimicrobials as a prophylaxis may reduce infections in a few patients with acute liver failure, but has no survival benefit.<ref name="pmid12949721">{{cite journal |author=Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT |title=Infection and the progression of hepatic encephalopathy in acute liver failure |journal=[[Gastroenterology]] |volume=125 |issue=3 |pages=755–64 |year=2003 |month=September |pmid=12949721 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0016508503010515 |accessdate=2012-10-26}}</ref>
* The use of [[antimicrobials]] as a [[prophylaxis]] may reduce infections in a few patients with acute liver failure, but has no survival benefit.<ref name="pmid12949721">{{cite journal |author=Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT |title=Infection and the progression of hepatic encephalopathy in acute liver failure |journal=[[Gastroenterology]] |volume=125 |issue=3 |pages=755–64 |year=2003 |month=September |pmid=12949721 |doi= |url=http://linkinghub.elsevier.com/retrieve/pii/S0016508503010515 |accessdate=2012-10-26}}</ref>
* If prophylaxis is not started, there should be ongoing surveillance for the development of infections.
* If prophylaxis is not started, there should be ongoing surveillance for the development of infections.
* The antibiotics are administered preemptively in patients with organ failure, encephalopathy or coagulopathy and in whom illness progression is considered likely. The high standards of infection control should be practiced to minimize the nosocomial sepsis.
* The antibiotics are administered preemptively in patients with organ failure, [[encephalopathy]] or [[coagulopathy]] and in whom illness progression is considered likely. The high standards of infection control should be practiced to minimize the [[Nosocomial infection|nosocomial sepsis]].


===Coagulopathy and Bleeding Complications===
===Coagulopathy and Bleeding Complications===
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* If there is no evidence of bleeding and INR is not in the normal range, treating the [[INR]] with fluids such as plasma may lead to volume overload and may cause transfusion-related lung injury.
* If there is no evidence of bleeding and INR is not in the normal range, treating the [[INR]] with fluids such as plasma may lead to volume overload and may cause transfusion-related lung injury.
* [[Vitamin K]] should be administered routinely (5- 10 mg SC) as there is a decreased synthesis of clotting factors from the liver tissue.
* [[Vitamin K]] should be administered routinely (5- 10 mg SC) as there is a decreased synthesis of clotting factors from the liver tissue.
* In high-risk procedures or clinically significant bleeding, clotting factor deficiencies should be treated.
* In high-risk procedures or clinically significant bleeding, [[clotting factor]] deficiencies should be treated.
* Bleeding mainly occurs from the [[capillaries]], and is usually from mucosal surfaces of the stomach and lung.  
* Bleeding mainly occurs from the [[capillaries]], and is usually from [[Mucous membrane|mucosal surfaces]] of the stomach and lung.  
* The mucosal surfaces of the gastrointestinal tract are the most common source of bleeding. So, the patient should receive stress ulcer prophylaxis with proton pump inhibitors or H2 blocking agents.
* The mucosal surfaces of the [[gastrointestinal tract]] are the most common source of bleeding. So, the patient should receive [[stress ulcer]] prophylaxis with [[Proton pump inhibitor|proton pump inhibitors]] or [[H2 antagonist|H2 blocking agents]].


===Hemodynamic and Metabolic Disturbances===
===Hemodynamic and Metabolic Disturbances===
* Decreased tissue perfusion leading to poor oxygenation and multi-organ failure is a major concern in acute liver failure.
* Decreased tissue perfusion leading to [[Oxygenation|poor oxygenation]] and [[multiorgan failure]] is a major concern in acute liver failure.
* Patients should be resuscitated with normal saline first, then half normal saline containing 75 mEq/L of [[bicarbonate]] should be used in acidotic patients. This fluid should be administered before the use of [[vasopressors]].
* Patients should be resuscitated with [[normal saline]] first, then half normal saline containing 75 mEq/L of [[bicarbonate]] should be used in [[Acidosis|acidotic]] patients. This fluid should be administered before the use of [[vasopressors]].
* For hypoglycemia, a [[dextrose]] solution should be used.
* For hypoglycemia, a [[dextrose]] solution should be used.
* If a patient is not responding to fluid or vasopressors, the infusion rate should be slowed down to prevent intense vaso-constriction causing [[ischemia]] of tissues.
* If a patient is not responding to fluid or [[vasopressors]], the infusion rate should be slowed down to prevent intense [[vasoconstriction]] causing [[ischemia]] of tissues.
* In patients progressing to [[acute renal failure]], care must be taken to avoid [[NSAID]]s and nephrotoxic agents. [[Dialysis]] should be used in a continuous mode rather than intermittent mode.
* In patients progressing to [[acute renal failure]], care must be taken to avoid [[NSAID]]s and [[Nephrotoxic|nephrotoxic agents]]. [[Dialysis]] should be used in a continuous mode rather than intermittent mode.
* Continuous monitoring of [[glucose]] and [[electrolytes]] is required as they may worsen the condition further.
* Continuous monitoring of [[glucose]] and [[electrolytes]] is required as they may worsen the condition further.
===Renal and pulmonary complications===
===Renal and pulmonary complications===
* Renal failure can develop in more than 50% of patients with acute liver failure more commonly in the elderly and in patients with acetaminophen-induced acute liver failure.
* [[Renal failure]] may develop in more than 50% of patients with acute liver failure, more commonly in the elderly and in patients with [[acetaminophen]] induced acute liver failure.
* In patients requiring dialysis, the continuous rather than intermittent is preferred as it achieves better metabolic and hemodynamic stability.
* [[Pulmonary edema]] and [[infections]] can be seen with acute liver failure. [[Mechanical ventilation]] can be required to ensure adequate [[oxygenation]].  
* Pulmonary edema and infections can be seen with acute liver failure. Mechanical ventilation can be required to ensure adequate oxygenation.  
*The [[Positive end expiratory pressure|positive end expiration pressure (PEEP)]] should be used with caution as it can aggravate [[cerebral edema]] in the acute liver failure patients.
*The positive end expiration pressure (PEEP) should be used with caution as it can aggravate cerebral edema in the acute liver failure patients.


==Treatment for the Specific Underlying Cause==
==Treatment for the Specific Underlying Cause==


===Acetaminophen Poisoning===
===Acetaminophen Poisoning===
*[[Acetylcysteine]] is used for [[acetaminophen poisoning]] up to 72 hours after ingestion.
*[[Acetylcysteine]] is used for [[Acetaminophen toxicity|acetaminophen poisoning]] for up to 72 hours after ingestion.
* Acetylcysteine can dramatically improve the outcome if administered within eight hours of acetaminophen ingestion.
* [[Acetylcysteine]] can dramatically improve the outcome if administered within eight hours of [[acetaminophen]] ingestion.
* Acetylcysteine improves cerebral blood flow and increases transplant-free survival in patients with stage 1 or 2 [[encephalopathy]] due to the hepatic failure of any cause.
* [[Acetylcysteine]] improves [[cerebral blood flow]] and increases transplant free survival in patients with stage 1 or 2 [[encephalopathy]] due to the [[hepatic failure]] of any cause.
* The patients with acute liver failure may not have a clear history of acetaminophen intake. Therefore, the threshold of administering acetylcysteine should be low and can also be administered in an acute liver failure of unknown etiology.
* Patients with acute liver failure may not have a clear history of [[acetaminophen]] intake. Therefore, the threshold for administering [[acetylcysteine]] should be low and can also be administered in an acute liver failure of unknown etiology.


===Mushroom Poisoning===
===Mushroom Poisoning===
* In mushroom poisoning, the early administration of activated charcoal is recommended as it is associated with improved survival.  
* In mushroom poisoning, the early administration of [[activated charcoal]] is recommended as it is associated with improved survival.  
* Aditional therapy include [[Penicillin G]] - 300,000 to 1 million units/kg/day
* Aditional therapy include [[Penicillin G]] - 300,000 to 1 million units/kg/day


===Drug Induced Hepatoxicity===
===Drug Induced Hepatoxicity===
* The drugs other than acetaminophen mostly cause acute liver failure by idiosyncratic reactions.
* The drugs other than [[acetaminophen]] mostly cause acute liver failure by [[Idiosyncratic drug reaction|idiosyncratic reactions]].
* No specific antidotes exist for these idiosyncratic drug reactions.
* No specific antidotes exist for these [[Idiosyncratic drug reaction|idiosyncratic drug reactions]].
* [[Corticosteroid]]s are not indicated unless a drug hypersensitivity or an autoimmune reaction is suspected.
* [[Corticosteroid]]s are not indicated unless a drug [[hypersensitivity]] or an [[autoimmune reaction]] is suspected.
* Discontinue all but essential medications.
* Discontinue all but essential medications.


===Viral Hepatitis===
===Viral Hepatitis===
* Supportive care
* Supportive care
* Viral hepatitis A (and E) related acute liver failure must be treated with supportive care as no virus-specific treatment has proven to be effective.
* [[Viral hepatitis]] A (and E) related acute liver failure must be treated with supportive care as no virus specific treatment has proven to be effective.
* [[Nucleoside analogs]] should be considered for [[hepatitis B]] associated acute liver failure and for prevention of post transplant recurrence.


===Herpes Simplex Hepatitis===
===Herpes Simplex Hepatitis===
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===Wilson's Disease===
===Wilson's Disease===
* [[Plasmapheresis]] + [[D-penicillamine]] are used in [[Wilson's disease]].
* [[Plasmapheresis]] + [[D-penicillamine]] are used in [[Wilson's disease]].
* Liver transplantaion.
* [[Liver transplantation|Liver transplantaion]].


===Autoimmune Hepatitis===
===Autoimmune Hepatitis===
* Patients with [[autoimmune hepatitis]] are candidates for [[corticosteroid]] therapy.<ref name="pmid23090425">{{cite journal |author=Czaja AJ |title=Acute and Acute Severe (Fulminant) Autoimmune Hepatitis |journal=[[Digestive Diseases and Sciences]] |volume= |issue= |pages= |year=2012 |month=October |pmid=23090425 |doi=10.1007/s10620-012-2445-4 |url= |accessdate=2012-10-26}}</ref>
* Patients with [[autoimmune hepatitis]] are candidates for [[corticosteroid]] therapy.<ref name="pmid23090425">{{cite journal |author=Czaja AJ |title=Acute and Acute Severe (Fulminant) Autoimmune Hepatitis |journal=[[Digestive Diseases and Sciences]] |volume= |issue= |pages= |year=2012 |month=October |pmid=23090425 |doi=10.1007/s10620-012-2445-4 |url= |accessdate=2012-10-26}}</ref>
* These patients should be considered for [[liver transplant|liver transplantation]] without delaying assessment to consider steroid therapy.
* These patients should be considered for [[liver transplant|liver transplantation]] without delaying assessment to consider [[steroid]] therapy.


===HELLP Syndrome===
===HELLP Syndrome===
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===Shock Liver===
===Shock Liver===
* Treatment of underlying cause of ischemia in [[shock liver]] is very important, and determines the prognosis of the condition.
* Treatment of underlying cause of [[ischemia]] in [[shock liver]] is very important, and determines the prognosis of the condition.
* Transplantation is seldom indicated.
* Transplantation is seldom indicated.


===Budd-Chiari Syndrome===
===Budd-Chiari Syndrome===
* Transplantation is considered after confirming the diagnosis [[Budd-Chiari syndrome]] and excluding malignancy for venous decompression.<ref name="pmid7737640">{{cite journal |author=Ringe B, Lang H, Oldhafer KJ, Gebel M, Flemming P, Georgii A, Borst HG, Pichlmayr R |title=Which is the best surgery for Budd-Chiari syndrome: venous decompression or liver transplantation? A single-center experience with 50 patients |journal=[[Hepatology (Baltimore, Md.)]] |volume=21 |issue=5 |pages=1337–44 |year=1995 |month=May |pmid=7737640 |doi= |url= |accessdate=2012-10-26}}</ref>
* Transplantation is considered after confirming the diagnosis [[Budd-Chiari syndrome]] and excluding [[malignancy]] for venous decompression.<ref name="pmid7737640">{{cite journal |author=Ringe B, Lang H, Oldhafer KJ, Gebel M, Flemming P, Georgii A, Borst HG, Pichlmayr R |title=Which is the best surgery for Budd-Chiari syndrome: venous decompression or liver transplantation? A single-center experience with 50 patients |journal=[[Hepatology (Baltimore, Md.)]] |volume=21 |issue=5 |pages=1337–44 |year=1995 |month=May |pmid=7737640 |doi= |url= |accessdate=2012-10-26}}</ref>
 
===Liver Support Systems===
[[Liver support systems]] are support devices which help in resting the liver to provide it some time to recover. These can also be used as a bridge to transplantation.  There are two kinds of devices; sorbent based artificial systems and cell based bio-artificial systems. There is no good evidence showing a decrease in mortality with their use in acute liver failure<ref name="pmid18336699">{{cite journal |author=Freeman RB, Steffick DE, Guidinger MK, Farmer DG, Berg CL, Merion RM |title=Liver and intestine transplantation in the United States, 1997-2006 |journal=[[American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons]] |volume=8 |issue=4 Pt 2 |pages=958–76 |year=2008 |month=April |pmid=18336699 |doi=10.1111/j.1600-6143.2008.02174.x |url=http://dx.doi.org/10.1111/j.1600-6143.2008.02174.x |accessdate=2012-10-26}}</ref>. They are not currently recommended outside of clinical trials.
==2011 AASLD Recommendations for Acute Liver Failure (DO NOT EDIT) <ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>==
===General Measures (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref> ===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>Patients with ALF should be hospitalized and monitored frequently, preferably in an ICU.<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>The precise etiology of ALF should be sought to guide further management decisions.<nowiki>"</nowiki>
|}
 
===Encephalopathy and Intracranial Pressure (DO NOT EDIT) <ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| '''1.''' <nowiki>"</nowiki>In ALF patients at highest risk for cerebral edema (serum ammonia > 150 lM, grade 3/4 hepatic encephalopathy, acute renal failure, requiring vasopressors to maintain MAP), the prophylactic induction of hypernatremia with hypertonic saline to a sodium level of 145-155 mEq/L is recommended.<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Corticosteroids should not be used to control elevated ICP in patients with ALF.<nowiki>"</nowiki>
|}
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class II-2]]
|-
| '''1.''' <nowiki>"</nowiki>In the event of intracranial hypertension, a mannitol bolus (0.5-1.0 gm/kg body weight) is recommended as first-line therapy; however, the prophylactic administration of mannitol is not recommended.<nowiki>"</nowiki>
|}
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class II-3]]
|-
| '''1.''' <nowiki>"</nowiki>Short-acting barbiturates and the induction of hypothermia to a core body temperature of 34-35<sup>o</sup>C may be considered for intracranial hypertension refractory to osmotic agents as a bridge to liver transplantation.<nowiki>"</nowiki>
|}
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>In early stages of encephalopathy, lactulose may be used either orally or rectally to effect a bowel purge, but should not be administered to the point of diarrhea, and may interfere with the surgical field by increasing bowel distention during liver  transplantation.<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Patients who progress to high-grade hepatic encephalopathy (grade III or IV) should undergo endotracheal intubation.<nowiki>"</nowiki>
|-
| '''3.''' <nowiki>"</nowiki>Seizure activity should be treated with phenytoin and benzodiazepines with short half-lives. Prophylactic phenytoin is not recommended.<nowiki>"</nowiki>
|-
| '''4.''' <nowiki>"</nowiki>Intracranial pressure monitoring is recommended in ALF patients with high grade hepatic encephalopathy, in centers with expertise in ICP monitoring, in patients awaiting and undergoing liver transplantation.<nowiki>"</nowiki>
|-
| '''5.''' <nowiki>"</nowiki>In the absence of ICP monitoring, frequent (hourly) neurological evaluation is recommended to identify early evidence of intracranial hypertension.<nowiki>"</nowiki>
|}
===Infections (DO NOT EDIT) <ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>Periodic surveillance cultures are recommended to detect bacterial and fungal pathogens as early as possible. Antibiotic treatment should be initiated promptly according to surveillance culture results at the earliest sign of active infection or  deterioration (progression to high grade hepatic encephalopathy or elements of the SIRS)<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Prophylactic antibiotics and antifungals have not been shown to improve overall outcomes in ALF and therefore cannot be advocated in all patients, particularly those with mild hepatic encephalopathy.<nowiki>"</nowiki>
 
|}
 
===Bleeding and Coagulopathy (DO NOT EDIT) <ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| '''1.''' <nowiki>"</nowiki>Patients with ALF in the ICU should receive prophylaxis with H<sub>2</sub> blocking agents or proton pump inhibitors (or sucralfate as a second-line agent) for acid-related gastrointestinal bleeding associated with stress.<nowiki>"</nowiki>
|}
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>Replacement therapy for thrombocytopenia and/or prolonged prothrombin time is recommended only in the setting of hemorrhage or prior to invasive procedures.<nowiki>"</nowiki>
|}
 
===Hemodynamic and Metabolic Disturbances (DO NOT EDIT) <ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| '''1.''' <nowiki>"</nowiki>If dialysis support is needed for acute renal failure, it is recommended that a continuous mode rather than an intermittent mode be used.<nowiki>"</nowiki>
|}
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class II]]
|-
| '''1.''' <nowiki>"</nowiki>Goals of circulatory support in patients with ALF are a MAP 75 mmHg and CPP 60-80 mmHg.<nowiki>"</nowiki>
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class II-1]]
|-
| '''2.''' <nowiki>"</nowiki>Systemic vasopressor support with agents such as norepinephrine should be administered in volume refractory hypotension or to ensure adequate CPP. Vasopressin or terlipressin can be added to norepinephrine in norepinephrine-refractory cases, but should be used  cautiously in severely encephalopathic patients with intracranial hypertension.<nowiki>"</nowiki>
|}
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>Fluid resuscitation and maintenance of adequate intravascular volume are recommended on presentation in patients with ALF. The initial treatment of hypotension should be with intravenous normal saline.<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Pulmonary artery catheterization is rarely necessary in patients with ALF and is associated with significant morbidity. Instead, appropriate volume status should be ensured with a volume challenge.<nowiki>"</nowiki>
|-
| '''3.''' <nowiki>"</nowiki>Metabolic homeostasis must be carefully maintained in ALF patients. Overall nutritional status as well as glucose, phosphate, potassium and magnesium levels should be monitored frequently, with expeditious correction of derangement's.<nowiki>"</nowiki>
 
|}
===Acetaminophen Hepatotoxicity (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| '''1.''' <nowiki>"</nowiki>For patients with known or suspected acetaminophen overdose within 4 hours of presentation, give activated charcoal just prior to starting NAC dosing.<nowiki>"</nowiki>
 
|}
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class II-1]]
|-
| '''1.''' <nowiki>"</nowiki>Begin NAC promptly in all patients where the quantity of acetaminophen ingested, serum drug level or rising aminotransferases indicate impending or evolving liver injury.<nowiki>"</nowiki>
 
|}
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>NAC may be used in cases of acute liver failure in which acetaminophen ingestion is possible or when knowledge of circumstances surrounding admission is inadequate but aminotransferases suggest acetaminophen poisoning.<nowiki>"</nowiki>
 
|}
===Mushroom Poisoning (DO NOT EDIT) <ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>In ALF patients with known or suspected mushroom poisoning, consider administration of penicillin G and N-acetylcysteine.<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Patients with acute liver failure secondary to mushroom poisoning should be listed for transplantation, as this procedure is often the only lifesaving option.<nowiki>"</nowiki>
 
|}
===Drug Induced Hepatoxicity (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| '''1.''' <nowiki>"</nowiki>N-acetylcysteine may be beneficial for acute liver failure due to drug-induced liver injury.<nowiki>"</nowiki>
|}
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>Obtain details (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary supplements taken over the past year.<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Determine ingredients of non-prescription medications whenever possible.<nowiki>"</nowiki>
|-
| '''3.''' <nowiki>"</nowiki>In the setting of acute liver failure due to possible drug hepatotoxicity, discontinue all but essential medications.<nowiki>"</nowiki>
|}
===Viral Hepatitis (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>Viral hepatitis A (and E) related acute liver failure must be treated with supportive care as no virus specific treatment has proven to be effective.<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Nucleos(t)ide analogues should be considered for hepatitis B-associated acute liver failure and for prevention of post-transplant recurrence.<nowiki>"</nowiki>
|}
===Herpes Simplex Hepatitis (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>Patients with known or suspected herpes virus or [[varicella zoster]] as the cause of acute liver failure should be treated with [[acyclovir]] (5-10 mg/kg IV every 8 hours) and may be considered for transplantation.<nowiki>"</nowiki>
 
|}
 
===Wilson Disease (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>To exclude Wilson disease one should obtain ceruloplasmin, serum and urinary copper levels, slit lamp examination for Kayser-Fleischer rings, hepatic copper levels when liver biopsy is feasible, and total bilirubin/alkaline phosphatase ratio.<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Patients in whom Wilson disease is the likely cause of acute liver failure must be promptly considered for liver transplantation.<nowiki>"</nowiki>
 
|}
 
===Autoimmune Hepatitis (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>Patients with coagulopathy and mild hepatic encephalopathy due to autoimmune hepatitis may be considered for corticosteroid treatment (prednisone, 40-60 mg/day).<nowiki>"</nowiki>
|-
| '''2.''' <nowiki>"</nowiki>Patients with autoimmune hepatitis should be considered for transplantation even while corticosteroids are being administered.<nowiki>"</nowiki>
 
|}
 
===HELLP Syndrome (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>For acute fatty liver of pregnancy or the HELLP syndrome, expeditious delivery of the infant is recommended.Transplantation may need to be considered if hepatic failure does not resolve quickly following delivery.<nowiki>"</nowiki>
 
|}
===Shock Liver (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class III]]
|-
| '''1.''' <nowiki>"</nowiki>In ALF patients with evidence of ischemic injury, cardiovascular support is the treatment of choice.<nowiki>"</nowiki>
|}
===Budd-Chiari Syndrome (DO NOT EDIT)<ref name="urlwww.aasld.org">{{cite web |url=http://www.aasld.org/practiceguidelines/Documents/AcuteLiverFailureUpdate2011.pdf |title=www.aasld.org |format= |work= |accessdate=2012-10-26}}</ref>===
 
{| class="wikitable"
|-
| style="text-align:center" | [[AASLD guidelines classification scheme#Classification of Recommendations|Class II-3]]
|-
| '''1.''' <nowiki>"</nowiki>Hepatic vein thrombosis with acute hepatic failure is an indication for liver transplantation, provided underlying malignancy is excluded.<nowiki>"</nowiki>
|}
 
===Therapeutic Approach===
Shown below are lists of recommendations of therapeutic approachs of acute liver failure based on the 2011 American Association for the Study of Liver Diseases (AASLD) position paper on acute liver failure.<ref name="Lee-2012">{{Cite journal  | last1 = Lee | first1 = WM. | last2 = Stravitz | first2 = RT. | last3 = Larson | first3 = AM. | title = Introduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011. | journal = Hepatology | volume = 55 | issue = 3 | pages = 965-7 | month = Mar | year = 2012|doi = 10.1002/hep.25551 | PMID = 22213561 }}</ref>
 
<div class="mw-collapsible mw-collapsed">
====Intensive Care Unit Management====
<div class="mw-collapsible-content">
{| class="wikitable"
!Organ System !!Specific Issues !! Management Recommendations
|-
| rowspan="3" |'''Central Nervous System'''||'''Cerebral edema and intracranial hypertension'''||a) '''Intracranial pressure monitoring: (III)'''
 
:❑ ICP monitoring with monitors when patients
 
::❑ Present with high grade hepatic encephalopathy (grade III/IV)
 
::❑ Are in centers with expertise in ICP monitoring
 
::❑ Are awaiting and undergoing liver transplantation
 
:❑ Correct coagulopathy before ICP monitoring with monitors
 
:❑ In the absence of ICP monitors
::❑ Hourly neurological evaluation
::❑ Monitoring of serum ammonia levels
::❑ Transcranial ultrasonography
 
b) '''Prophylactic hypertonic saline: (I)''':❑ Hypertonic saline i.v bolus (20 ml of 30% sodium chloride or 200 ml of 3% sodium chloride)<ref name="Wendon-2008">{{Cite journal  | last1 = Wendon | first1 = J. | last2 = Lee | first2 = W. | title = Encephalopathy and cerebral edema in the setting of acute liver failure: pathogenesis and management. | journal = Neurocrit Care | volume = 9 | issue = 1 | pages = 97-102 | month =  | year = 2008 | doi = 10.1007/s12028-008-9123-6 | PMID = 18688582 }}</ref> for prophylactic induction of [[hypernatremia]] in patients with
 
::❑ Serum ammonia >150 μM
 
::❑ Grade III/IV hepatic encephalopathy
 
::❑ [[Acute renal failure]]
 
::❑ [[Vasopressors]] requirement to maintain [[Mean arterial pressure|MAP]]
 
:❑ Maintain serum sodium level of 145-155 mEq/L
 
c) '''Intracranial hypertension treatment:'''
 
:❑ I line therapy: '''(II-2)'''
 
::❑ [[Mannitol]] i.v bolus (0.5-1.0 gm/kg of body weight or 2 ml of 20% solution/kg of body weight)<ref name="Wendon-2008">{{Cite journal  | last1 = Wendon | first1 = J. | last2 = Lee | first2 = W. | title = Encephalopathy and cerebral edema in the setting of acute liver failure: pathogenesis and management. | journal = Neurocrit Care | volume = 9 | issue = 1 | pages = 97-102 | month =  | year = 2008 | doi = 10.1007/s12028-008-9123-6 | PMID = 18688582 }}</ref>
 
::❑ Administered as needed as long as serum osmolality <320 mOsm/L
 
:❑ II line therapy: (if refractory to mannitol) '''(II-3)'''
 
::❑ [[Secobarbital|Short-acting barbiturates]]
::❑ [[Hypothermia]] induction to a core body temperature of 34°-35°C
::❑ Indomethacin i.v bolus (0.5 mg/kg) may be used when cerebral hyperemia is also present<ref name="Wendon-2008">{{Cite journal  | last1 = Wendon | first1 = J. | last2 = Lee | first2 = W. | title = Encephalopathy and cerebral edema in the setting of acute liver failure: pathogenesis and management. | journal = Neurocrit Care | volume = 9 | issue = 1 | pages = 97-102 | month =  | year = 2008 | doi = 10.1007/s12028-008-9123-6 | PMID = 18688582 }}</ref>
 
:❑ Goals of intracranial hypertension treatment<ref name="Hoofnagle-1995">{{Cite journal  | last1 = Hoofnagle | first1 = JH. | last2 = Carithers | first2 = RL. | last3 = Shapiro | first3 = C. | last4 = Ascher | first4 = N. | title = Fulminant hepatic failure: summary of a workshop. | journal = Hepatology | volume = 21 | issue = 1 | pages = 240-52 | month = Jan | year = 1995 | doi =  | PMID = 7806160 }}</ref>
 
::ICP <20 mmHg
 
::CPP >60 mmHg
 
:❑ Hyperventilate to PaCO2 of 25-30 mmHg (in case of impending herniation)<ref name="Laffey-2002">{{Cite journal  | last1 = Laffey | first1 = JG. | last2 = Kavanagh | first2 = BP. | title = Hypocapnia. | journal = N Engl J Med | volume = 347 | issue = 1 | pages = 43-53 | month = Jul | year = 2002 | doi = 10.1056/NEJMra012457 | PMID = 12097540 }}</ref>
|-
| '''Grade I/II encephalopathy'''|| ❑ Frequent neurological assessment with avoidance of stimulation and sedation<br> ❑ Small doses of short-acting [[benzodiazepines]] in case of unmanageable agitation<br> ❑ Stat brain [[CT]] to rule out other causes of altered mental status<br> ❑ Consideration for transfer to a liver transplant facility and listing for transplantation at the earliest<br> ❑ [[Lactulose]] (possibly helpful and may interfere with surgical field by increasing bowel distention during liver transplantation) '''(III)'''<br> ❑ Infection surveillance<br>  ❑ Antibiotic prophylaxis against infections (possibly helpful)<br> ❑ Infection treatment as required
|-
| '''Grade III/IV encephalopathy'''||Besides managing the patient similar to grade I/II encephalopathy
:❑ Intubate trachea (might require sedation) '''(III)'''
:❑ Muscle relaxants for intubation<ref name="Stravitz-2009">{{Cite journal  | last1 = Stravitz | first1 = RT. | last2 = Kramer | first2 = DJ. | title = Management of acute liver failure. | journal = Nat Rev Gastroenterol Hepatol | volume = 6 | issue = 9 | pages = 542-53 | month = Sep | year = 2009 | doi = 10.1038/nrgastro.2009.127 | PMID = 19652652 }}</ref><ref name="Wijdicks-2002">{{Cite journal  | last1 = Wijdicks | first1 = EF. | last2 = Nyberg | first2 = SL. | title = Propofol to control intracranial pressure in fulminant hepatic failure. | journal = Transplant Proc | volume = 34 | issue = 4 | pages = 1220-2 | month = Jun | year = 2002 | doi =  | PMID = 12072321 }}</ref>
::During intubation: [[Atracurium|Depolarizing neuro-muscular blocking agents]]
::After intubation: [[Propofol]]
:❑ Elevate head of bed to 30°<ref name="Durward-1983">{{Cite journal  | last1 = Durward | first1 = QJ. | last2 = Amacher | first2 = AL. | last3 = Del Maestro | first3 = RF. | last4 = Sibbald | first4 = WJ. | title = Cerebral and cardiovascular responses to changes in head elevation in patients with intracranial hypertension. | journal = J Neurosurg | volume = 59 | issue = 6 | pages = 938-44 | month = Dec | year = 1983 | doi = 10.3171/jns.1983.59.6.0938 | PMID = 6631516 }}</ref>
:❑ [[Lidocaine]] administration during endotracheal suctioning
:❑ Immediate treatment of seizures with [[phenytoin]] and [[benzodiazepines]] with short half-lives '''(III)'''
:❑ ICP monitoring with devices
:❑ Mannitol administration following severe elevation of ICP or first clinical sign of herniation
:❑ Hypertonic saline administration to raise serum sodium to 145-155 mmol/L
:❑ Hyperventilate patient in case of impending herniation
:❑ Monitor and manage hemodynamic and renal parameters as well as glucose, electrolytes and acid/base status
|-
| '''Cardiovascular System'''|| '''Hemodynamic abnormalities'''|| ❑ Fluid resuscitation and maintenance of adequate intravascular volume (initiate hypotension treatment with intravenous normal saline) '''(III)'''<br> ❑ Systemic vasopressor support ([[dopamine]], [[epinephrine]], [[norepinephrine]]) as needed '''(II-1)'''<br> ❑ [[Vasopressin]]or[[terlipressin]] added to norepinephrine in norepinephrine-refractory cases (used cautiously in severely encephalopathic patients with intracranial hypertension) '''(II-1)'''<br> ❑ Ensure appropriate volume status with a volume challenge (pulmonary artery catheterization is rarely necessary since it is associated with significant morbidity) '''(III)'''<br> ❑ [[Echocardiography]] for low cardiac output and right ventricular failure<br> ❑ Goals of circulatory support: '''(II)'''
: MAP ≥75 mmHg
: [[CPP]] 60-80 mmHg
|-
|'''Respiratory System'''|| '''Aspiration pneumonitis'''|| ❑ Neurologic observation to monitor level of consciousness<br> ❑ Early endotracheal intubation for depressed level of consciousness
|-
|'''Hepatic System'''||'''Hepatic dysfunction'''|| ❑ NAC administration (acetaminophen as well as non-acetaminophen ALF)
|-
| '''Metabolic and Renal System'''|| '''Metabolic abnormalities and renal failure'''|| ❑ Frequent monitoring and correction of derangements in glucose, potassium, magnesium and phosphate '''(III)'''<br> ❑ Continuous modes of hemodialysis (if needed) '''(I)'''
|-
| '''Hematologic System'''|| '''Coagulopathy'''|| ❑ Replacement therapy for [[thrombocytopenia]] and/or prolonged prothrombin time with platelet and [[FFP]] transfusion respectively in the setting of active bleeding or before invasive procedure '''(III)'''<br> ❑ [[Vitamin K]] (5-10 mg subcutaneously) (at least one dose)<ref name="Pereira-2005">{{Cite journal  | last1 = Pereira | first1 = SP. | last2 = Rowbotham | first2 = D. | last3 = Fitt | first3 = S. | last4 = Shearer | first4 = MJ. | last5 = Wendon | first5 = J. | last6 = Williams | first6 = R. | title = Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease. | journal = J Hepatol | volume = 42 | issue = 3 | pages = 365-70 | month = Mar | year = 2005 | doi = 10.1016/j.jhep.2004.11.030 | PMID = 15710219 }}</ref><br> ❑ Plasmapheresis or recombinant activated factor VII (rFVIIa) in case of inadequate correction of severely elevated INR and risks of volume overload<br> ❑ Maintenance of adequate platelet count
:In the absence of bleeding: >10,000/mm<sup>3</sup><ref name="Heckman-1997">{{Cite journal  | last1 = Heckman | first1 = KD. | last2 = Weiner | first2 = GJ. | last3 = Davis | first3 = CS. | last4 = Strauss | first4 = RG. | last5 = Jones | first5 = MP. | last6 = Burns | first6 = CP. | title = Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL. | journal = J Clin Oncol | volume = 15 | issue = 3 | pages = 1143-9 | month = Mar | year = 1997 | doi =  | PMID = 9060557 }}</ref>
:For performing invasive procedures: 50-70,000/ mm<sup>3</sup><br>
❑ Prophylaxis for stress ulceration: '''(I)'''
:❑ I line: [[H2 blocker]] or [[PPI]]
:❑ II line: [[Sucralfate]]
|-
| '''Immunologic System'''|| '''Infection'''|| ❑ Periodic surveillance for prompt initiation of antimicrobial treatment of infections at the earliest sign of active infection or deterioration (progression to high grade hepatic encephalopathy or elements of the [[SIRS]]) '''(III)'''<br> ❑ Antibiotic prophylaxis (possibly helpful in patients with coagulopathy, organ failure, encephalopathy and in whom illness progression is considered likely - not proven) '''(III)'''
|}
</div></div>
<div class="mw-collapsible mw-collapsed">
 
====Etiology Specific Management====
<div class="mw-collapsible-content">
{| class="wikitable sortable"
{| class="wikitable sortable"
!Etiology
!Etiology
Line 438: Line 108:
!Management Recommendations
!Management Recommendations
|-
|-
|'''Acetaminophen toxicity''' ||❑ H/o of acetaminophen intake (toxic dose >10 gm/day or >150 mg/kg)<BR>❑ Acetaminophen in blood and/or urine<BR>❑ [[Aminotransferase]] levels >3500 IU/L with low bilirubin levels, in the absence of apparent hypotension or cardiovascular collapse (suspected acetaminophen toxicity in the absence of a positive history because acetaminophen is the leading cause of ALF at least in the United States and Europe)<ref name="Ostapowicz-2002">{{Cite journal  | last1 = Ostapowicz | first1 = G. | last2 = Fontana|first2 = RJ. | last3 = Schiødt | first3 = FV. | last4 = Larson | first4 = A. | last5 = Davern | first5 = TJ. | last6 = Han | first6 = SH. | last7 = McCashland|first7 = TM. | last8 = Shakil | first8 = AO. | last9 = Hay | first9 = JE. | title = Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. | journal = Ann Intern Med | volume = 137 | issue = 12 | pages = 947-54 | month = Dec | year = 2002 | doi =  | PMID = 12484709 }}</ref>||❑'''Activated charcoal:'''<br>1g/kg PO within 1 hour after drug ingestion (may be beneficial even when administered within 3-4 hours after ingestion)<ref name="Sato-2003">{{Cite journal  | last1 = Sato | first1 = RL. | last2 = Wong | first2 = JJ. | last3 = Sumida | first3 = SM. | last4 = Marn | first4 = RY. | last5 = Enoki | first5 = NR. | last6 = Yamamoto | first6 = LG. | title = Efficacy of superactivated charcoal administered late (3 hours) after acetaminophen overdose. | journal = Am J Emerg Med | volume = 21 | issue = 3 | pages = 189-91 | month = May | year = 2003 | doi =  | PMID = 12811710 }}</ref> and prior to starting [[NAC]] '''(I)'''<br>❑ '''[[Nomogram]]''' (helps determining the likelihood of serious liver damage but does not exclude possible toxicity)<br>❑ '''NAC:''' <br>140 mg/kg PO or through NGT (diluted to 5% solution), then 70 mg/kg PO q4h x 17 doses<br>'''or'''<br>IV loading dose of 150 mg/kg in 5% dextrose over 15 minutes, then maintenance dose of 50 mg/kg IV over the next 4 hours and then 100 mg/kg IV over the following 16 hours<br>*Promptly begin NAC (beneficial even when administered <48 hours after drug ingestion) in all patients with impending or evolving liver injury due to acetaminophen '''(II-1)'''<br>*NAC may be used in cases of ALF due to suspected acetaminophen poisoning '''(III)'''<br>*NAC is recommended even in case of non-acetaminophen ALF<ref name="Lee-2009">{{Cite journal  | last1 = Lee | first1 = WM. | last2 = Hynan | first2 = LS. | last3 = Rossaro | first3 = L. | last4 = Fontana | first4 = RJ. | last5 = Stravitz | first5 = RT. | last6 = Larson | first6 = AM. | last7 = Davern | first7 = TJ. | last8 = Murray | first8 = NG. | last9 = McCashland | first9 = T. | title = Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. | journal = Gastroenterology | volume = 137 | issue = 3 | pages = 856-64, 864.e1 | month = Sep | year = 2009 | doi = 10.1053/j.gastro.2009.06.006 | PMID = 19524577 }}</ref>
|'''Acetaminophen toxicity''' ||
|-
* History of [[acetaminophen]] intake (toxic dose >10 gm/day or >150 mg/kg)<BR>
|'''Acute fatty liver of pregnancy/HELLP''' ||❑ Jaundice and hypertension<br>❑ Coagulopathy<br>❑ Thrombocytopenia<br>❑ Proteinuria<br>❑ Hypoglycemia<br>❑ [[Steatosis]] in liver imaging or biopsy ||❑ Early diagnosis and prompt delivery '''(III)'''<br>❑ Adequate supportive care<br>❑ Consider transplantation for postpartum deterioration '''(III)'''
* [[Acetaminophen]] in blood and/or urine<BR>
|-
* [[Aminotransferase]] levels >3500 IU/L with low [[bilirubin]] levels, in the absence of apparent [[hypotension]] or [[cardiovascular collapse]] (suspected acetaminophen toxicity in the absence of a positive history because acetaminophen is the leading cause of ALF at least in the United States and Europe)<ref name="Ostapowicz-2002">{{Cite journal  | last1 = Ostapowicz | first1 = G. | last2 = Fontana|first2 = RJ. | last3 = Schiødt | first3 = FV. | last4 = Larson | first4 = A. | last5 = Davern | first5 = TJ. | last6 = Han | first6 = SH. | last7 = McCashland|first7 = TM. | last8 = Shakil | first8 = AO. | last9 = Hay | first9 = JE. | title = Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. | journal = Ann Intern Med | volume = 137 | issue = 12 | pages = 947-54 | month = Dec | year = 2002 | doi =  | PMID = 12484709 }}</ref>
|'''Acute ischemic injury''' ||❑ H/o cardiac arrest<br>❑ Any period of significant hypovolemia/hypotension, or severe [[CHF]] (hypotension is not documented always)<br>❑ Any associated renal dysfunction & muscle necrosis<br>❑ Elevated aminotransferase levels responding to fluid resuscitation||❑ Adequate cardiovascular support '''(III)'''
|
|-
* '''Activated charcoal:'''<br>1g/kg PO within 1 hour after drug ingestion (may be beneficial even when administered within 3-4 hours after ingestion) and prior to starting N-acetylcystine ([[NAC]]) .
|'''Autoimmune''' ||❑ Positive serum autoantibodies (may be absent)<br>❑ Positive liver biopsy (confirms diagnosis when [[autoimmune hepatitis]] is suspected and autoantibodies are negative) '''(III)''' ||❑ [[Prednisolone]] (start with 40-60 mg/day, especially in the presence of coagulopathy and mild hepatic encephalopathy) '''(III)'''<br>❑ Consider transplantation and do not delay while awaiting response to steroid treatment '''(III)'''
* '''[[Nomogram]]''' (helps to determine the likelihood of serious liver damage but does not exclude possible toxicity)<br>
|-
 
|'''Budd-Chiari''' ||❑ Abdominal pain<br>❑ Ascites<br> ❑ Hepatomegaly<br>❑ Blood tests positive for hypercoagulability<br>❑ Positive findings during liver imaging ([[CT]], [[Medical ultrasonography#Doppler sonography|doppler USG]], [[venography]] or magnetic resonance venography) (confirms diagnosis) ||❑ Liver transplantation (provided underlying malignancy is excluded) '''(II-3)'''
* N-acetylcystine ([[NAC]]) <br>140 mg/kg PO or through NGT (diluted to 5% solution), then 70 mg/kg PO q4h x 17 doses<br>'''or'''<br>IV loading dose of 150 mg/kg in 5% dextrose over 15 minutes, thethen a maintenance dose 50 mg/kg IV over the next 4 hours and 100 mg/kg IV over the following 16 hours<br>*Promptly begin NAC (beneficial even when administered <48 hours after drug ingestion) in all patients with impending or evolving liver injury due to acetaminophen.<br>
|-
|'''Drug induced''' ||❑ H/o hepatotoxic drug intake (usually idiosyncratic hepatotoxic drug intake within first 6 months after drug initiation; continuous usage of potentially hepatotoxic drug for more than 1 to 2 years is unlikely to cause de novo liver damage)<br>❑ H/o inclusive of details (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary supplements taken over the past year '''(III)'''<br>❑ Determine ingredients of non-prescription medications whenever possible '''(III)''' ||❑ Discontinue all but essential medications in the setting of possible drug hepatotoxicity '''(III)'''<br>❑ NAC (may be beneficial for ALF induced by drugs) '''(I)'''
|-
|'''Malignant infiltration''' ||❑ Massive hepatomegaly<br>❑ Malignant infiltration in liver imaging or liver biopsy (confirms or excludes diagnosis) '''(III)'''||❑ Appropriate management of underlying malignancy<br>❑ Supportive care
|-
|'''Mushroom poisoning''' ||❑ H/o recent mushroom intake<br>❑ Severe GI symptoms like nausea, vomiting and diarrhea within hours or a day of ingestion (suspected mushroom poisoning in the absence of a positive history) ||❑ Early gastric lavage and activated charcoal administration<br>❑ [[Penicillin|Penicillin G]] 300,000-1 million units/kg/day<br>'''or'''<br>[[Silibinin]] 30-40 mg/kg/day IV or PO, 3-4 days (silymarin in Europe and south America; milk thistle in north America)<ref name="Enjalbert-2002">{{Cite journal  | last1 = Enjalbert | first1 = F. | last2 = Rapior | first2 = S. | last3 = Nouguier-Soulé | first3 = J. | last4 = Guillon | first4 = S. | last5 = Amouroux | first5 = N. | last6 = Cabot | first6 = C. | title = Treatment of amatoxin poisoning: 20-year retrospective analysis. | journal = J Toxicol Clin Toxicol | volume = 40 | issue = 6 | pages = 715-57 | month =  | year = 2002 | doi =  | PMID = 12475187 }}</ref><br>❑ NAC '''(III)'''<br>❑ Liver transplantation (the only lifesaving option) '''(III)'''<br>❑ Fluid resuscitation (as needed)
|-
|'''Viral''' ||❑ Toxically appearing patients with skin lesions (HSV)<br>❑ Positive hepatitis virus serology<br>❑ [[HSV]] positive liver biopsy ||❑ Supportive treatment (no virus specific treatment proven to be effective) '''(III)'''<BR>❑ Nucleoside and nucleotide analogues (for [[HBV]] associated ALF) '''(III)'''<BR>❑ [[Acyclovir]] (5-10 mg/kg every 8 hours for at least 7 days for HSV or VZV) '''(III)'''
|-
|'''Wilson's disease''' ||❑ KF ring<br>❑ Serum bilirubin >20 mg/dL,<br>❑ Bilirubin:alkaline phosphatase >2.0<br>❑ Low serum ceruloplasmin<br>❑ Elevated serum & urine copper<br>❑ High copper levels in liver biopsy '''(III)'''||❑ Liver transplantation '''(III)'''<br>❑ Dialysis or hemofiltration or plasmapheresis or plasma exchange
|-
|'''Intermediate etiology''' ||❑ Etiology undetermined after all evaluation||❑ Review drug and toxin intake H/o<BR>❑ Transjugular biopsy (for further evaluation of possible mailgnancy, [[Wilson disease]], autoimmune hepatitis and [[viral hepatitis]]) '''(III)'''
|}
</div></div>
<div class="mw-collapsible mw-collapsed">
====Transplantation====
<div class="mw-collapsible-content">
{| class="wikitable"
! Liver Transplantation!! Recommendations
|-
| Prognostic scoring systems|| Currently available and widely applied prognostic scoring systems (King’s College Hospital criteria-KCH Criteria,<ref name="O'Grady-1989">{{Cite journal  | last1 = O'Grady | first1 = JG. | last2 = Alexander | first2 = GJ. | last3 = Hayllar | first3 = KM. | last4 = Williams | first4 = R. | title = Early indicators of prognosis in fulminant hepatic failure. | journal = Gastroenterology | volume = 97 | issue = 2 | pages = 439-45 | month = Aug | year = 1989 | doi =  | PMID = 2490426 }}</ref> Clichy Criteria,<ref name="Bernuau-1986">{{Cite journal  | last1 = Bernuau | first1 = J. | last2 = Rueff | first2 = B. | last3 = Benhamou | first3 = JP. | title = Fulminant and subfulminant liver failure: definitions and causes. | journal = Semin Liver Dis | volume = 6 | issue = 2 | pages = 97-106 | month = May | year = 1986 | doi = 10.1055/s-2008-1040593 | PMID = 3529410 }}</ref> and Japanese Criteria<ref name="Mochida-2008">{{Cite journal  | last1 = Mochida | first1 = S. | last2 = Nakayama | first2 = N. | last3 = Matsui | first3 = A. | last4 = Nagoshi | first4 = S. | last5 = Fujiwara | first5 = K. | title = Re-evaluation of the Guideline published by the Acute Liver Failure Study Group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis. | journal = Hepatol Res | volume = 38 | issue = 10 | pages = 970-9 | month = Oct | year = 2008 | doi = 10.1111/j.1872-034X.2008.00368.x | PMID = 18462374 }}</ref>) do not adequately predict outcome and determine candidacy for liver transplantation, thus not recommending the entire reliance entirely upon these guidelines '''(III)'''
|-
|-
| Urgent hepatic transplantation|| Urgent hepatic transplantation is indicated when prognostic indicators suggest a high likelihood of death '''(II-3)'''
|'''Acute fatty liver of pregnancy/HELLP''' ||
|-
* [[Jaundice]]  
| In the setting of limited organ supply|| In the setting of limited organ supply, either living donor or auxiliary liver transplantation may be considered.  But its use remains controversial '''(II-3)'''
* [[Hypertension]]<br>
|-
* [[Coagulopathy]]<br>
|Liver support systems|| Currently available liver support systems are not recommended outside clinical trials and their future in management of ALF remains unclear'''(II-1)'''
* [[Thrombocytopenia]]
|-
|}
</div></div>
====Intensive Care Unit Management====
<div class="mw-collapsible-content">
{| class="wikitable"
!Organ System !!Specific Issues !! Management Recommendations
|-
| rowspan="3" |'''Central Nervous System'''||'''Cerebral edema and intracranial hypertension'''||a) '''Intracranial pressure monitoring: (III)'''
 
:❑ ICP monitoring with monitors when patients
 
::❑ Present with high grade hepatic encephalopathy (grade III/IV)
 
::❑ Are in centers with expertise in ICP monitoring
 
::❑ Are awaiting and undergoing liver transplantation
 
:❑ Correct coagulopathy before ICP monitoring with monitors
 
:❑ In the absence of ICP monitors
::❑ Hourly neurological evaluation
::❑ Monitoring of serum ammonia levels
::❑ Transcranial ultrasonography
 
b) '''Prophylactic hypertonic saline: (I)''':❑ Hypertonic saline i.v bolus (20 ml of 30% sodium chloride or 200 ml of 3% sodium chloride)<ref name="Wendon-2008">{{Cite journal  | last1 = Wendon | first1 = J. | last2 = Lee | first2 = W. | title = Encephalopathy and cerebral edema in the setting of acute liver failure: pathogenesis and management. | journal = Neurocrit Care | volume = 9 | issue = 1 | pages = 97-102 | month =  | year = 2008 | doi = 10.1007/s12028-008-9123-6 | PMID = 18688582 }}</ref> for prophylactic induction of [[hypernatremia]] in patients with
 
::❑ Serum ammonia >150 μM
 
::❑ Grade III/IV hepatic encephalopathy
 
::❑ [[Acute renal failure]]
 
::❑ [[Vasopressors]] requirement to maintain [[Mean arterial pressure|MAP]]
 
:❑ Maintain serum sodium level of 145-155 mEq/L
 
c) '''Intracranial hypertension treatment:'''
 
:❑ I line therapy: '''(II-2)'''
 
::❑ [[Mannitol]] i.v bolus (0.5-1.0 gm/kg of body weight or 2 ml of 20% solution/kg of body weight)<ref name="Wendon-2008">{{Cite journal  | last1 = Wendon | first1 = J. | last2 = Lee | first2 = W. | title = Encephalopathy and cerebral edema in the setting of acute liver failure: pathogenesis and management. | journal = Neurocrit Care | volume = 9 | issue = 1 | pages = 97-102 | month =  | year = 2008 | doi = 10.1007/s12028-008-9123-6 | PMID = 18688582 }}</ref>
 
::❑ Administered as needed as long as serum osmolality <320 mOsm/L
 
:❑ II line therapy: (if refractory to mannitol) '''(II-3)'''
 
::❑ [[Secobarbital|Short-acting barbiturates]]
::❑ [[Hypothermia]] induction to a core body temperature of 34°-35°C
::❑ Indomethacin i.v bolus (0.5 mg/kg) may be used when cerebral hyperemia is also present<ref name="Wendon-2008">{{Cite journal  | last1 = Wendon | first1 = J. | last2 = Lee | first2 = W. | title = Encephalopathy and cerebral edema in the setting of acute liver failure: pathogenesis and management. | journal = Neurocrit Care | volume = 9 | issue = 1 | pages = 97-102 | month =  | year = 2008 | doi = 10.1007/s12028-008-9123-6 | PMID = 18688582 }}</ref>
 
:❑ Goals of intracranial hypertension treatment<ref name="Hoofnagle-1995">{{Cite journal  | last1 = Hoofnagle | first1 = JH. | last2 = Carithers | first2 = RL. | last3 = Shapiro | first3 = C. | last4 = Ascher | first4 = N. | title = Fulminant hepatic failure: summary of a workshop. | journal = Hepatology | volume = 21 | issue = 1 | pages = 240-52 | month = Jan | year = 1995 | doi =  | PMID = 7806160 }}</ref>
 
::ICP <20 mmHg


::CPP >60 mmHg
* [[Proteinuria]]
 
* [[Hypoglycemia]]
:❑ Hyperventilate to PaCO2 of 25-30 mmHg (in case of impending herniation)<ref name="Laffey-2002">{{Cite journal  | last1 = Laffey | first1 = JG. | last2 = Kavanagh | first2 = BP. | title = Hypocapnia. | journal = N Engl J Med | volume = 347 | issue = 1 | pages = 43-53 | month = Jul | year = 2002 | doi = 10.1056/NEJMra012457 | PMID = 12097540 }}</ref>
* [[Steatosis]] in liver imaging or biopsy
|-
|
| '''Grade I/II encephalopathy'''|| ❑ Frequent neurological assessment with avoidance of stimulation and sedation<br> ❑ Small doses of short-acting [[benzodiazepines]] in case of unmanageable agitation<br> ❑ Stat brain [[CT]] to rule out other causes of altered mental status<br> ❑ Consideration for transfer to a liver transplant facility and listing for transplantation at the earliest<br> ❑ [[Lactulose]] (possibly helpful and may interfere with surgical field by increasing bowel distention during liver transplantation) '''(III)'''<br> ❑ Infection surveillance<br>  ❑ Antibiotic prophylaxis against infections (possibly helpful)<br> ❑ Infection treatment as required
* Early diagnosis and prompt delivery.<br>
|-
* Adequate supportive care.<br>
| '''Grade III/IV encephalopathy'''||Besides managing the patient similar to grade I/II encephalopathy
* Consider transplantation for postpartum deterioration
:❑ Intubate trachea (might require sedation) '''(III)'''
:❑ Muscle relaxants for intubation<ref name="Stravitz-2009">{{Cite journal  | last1 = Stravitz | first1 = RT. | last2 = Kramer | first2 = DJ. | title = Management of acute liver failure. | journal = Nat Rev Gastroenterol Hepatol | volume = 6 | issue = 9 | pages = 542-53 | month = Sep | year = 2009 | doi = 10.1038/nrgastro.2009.127 | PMID = 19652652 }}</ref><ref name="Wijdicks-2002">{{Cite journal  | last1 = Wijdicks | first1 = EF. | last2 = Nyberg | first2 = SL. | title = Propofol to control intracranial pressure in fulminant hepatic failure. | journal = Transplant Proc | volume = 34 | issue = 4 | pages = 1220-2 | month = Jun | year = 2002 | doi =  | PMID = 12072321 }}</ref>
::During intubation: [[Atracurium|Depolarizing neuro-muscular blocking agents]]
::After intubation: [[Propofol]]
:❑ Elevate head of bed to 30°<ref name="Durward-1983">{{Cite journal  | last1 = Durward | first1 = QJ. | last2 = Amacher | first2 = AL. | last3 = Del Maestro | first3 = RF. | last4 = Sibbald | first4 = WJ. | title = Cerebral and cardiovascular responses to changes in head elevation in patients with intracranial hypertension. | journal = J Neurosurg | volume = 59 | issue = 6 | pages = 938-44 | month = Dec | year = 1983 | doi = 10.3171/jns.1983.59.6.0938 | PMID = 6631516 }}</ref>
:❑ [[Lidocaine]] administration during endotracheal suctioning
:❑ Immediate treatment of seizures with [[phenytoin]] and [[benzodiazepines]] with short half-lives '''(III)'''
:❑ ICP monitoring with devices
:❑ Mannitol administration following severe elevation of ICP or first clinical sign of herniation
:❑ Hypertonic saline administration to raise serum sodium to 145-155 mmol/L
:❑ Hyperventilate patient in case of impending herniation
:❑ Monitor and manage hemodynamic and renal parameters as well as glucose, electrolytes and acid/base status
|-
|-
| '''Cardiovascular System'''|| '''Hemodynamic abnormalities'''|| ❑ Fluid resuscitation and maintenance of adequate intravascular volume (initiate hypotension treatment with intravenous normal saline) '''(III)'''<br> ❑ Systemic vasopressor support ([[dopamine]], [[epinephrine]], [[norepinephrine]]) as needed '''(II-1)'''<br> ❑ [[Vasopressin]]or[[terlipressin]] added to norepinephrine in norepinephrine-refractory cases (used cautiously in severely encephalopathic patients with intracranial hypertension) '''(II-1)'''<br> ❑ Ensure appropriate volume status with a volume challenge (pulmonary artery catheterization is rarely necessary since it is associated with significant morbidity) '''(III)'''<br> ❑ [[Echocardiography]] for low cardiac output and right ventricular failure<br> ❑ Goals of circulatory support: '''(II)'''
|'''Acute ischemic injury''' ||
: MAP ≥75 mmHg
* History of cardiac arrest<br>
: [[CPP]] 60-80 mmHg
* Any period of significant hypovolemia/hypotension, or severe [[CHF]] (hypotension is not documented always)<br>
* Any associated [[Renal insufficiency|renal dysfunction]] & muscle [[necrosis]]<br>  
* Elevated aminotransferase levels responding to fluid resuscitation
|
* Adequate cardiovascular support.
|-
|-
|'''Respiratory System'''|| '''Aspiration pneumonitis'''|| ❑ Neurologic observation to monitor level of consciousness<br> ❑ Early endotracheal intubation for depressed level of consciousness
|'''Autoimmune''' ||
* Positive serum [[Autoantibody|autoantibodies]] (may be absent)<br>
* Positive liver biopsy (confirms diagnosis when [[autoimmune hepatitis]] is suspected and autoantibodies are negative)
|
*  [[Prednisolone]] (start with 40-60 mg/day, especially in the presence of coagulopathy and mild hepatic encephalopathy)
* Consider transplantation and do not delay while awaiting response to steroid treatment
|-
|-
|'''Hepatic System'''||'''Hepatic dysfunction'''|| ❑ NAC administration (acetaminophen as well as non-acetaminophen ALF)
|'''Budd-Chiari''' ||
* [[Abdominal pain|Abdominal pain<br>]]
*  [[Ascites]]<br>
*  [[Hepatomegaly]]<br>
*  Blood tests positive for [[hypercoagulability]]<br>
*  Positive findings during liver imaging ([[CT]], [[Medical ultrasonography#Doppler sonography|doppler USG]], [[venography]] or magnetic resonance venography) (confirms diagnosis)
|
* Liver transplantation (provided underlying malignancy is excluded)  
|-
|-
| '''Metabolic and Renal System'''|| '''Metabolic abnormalities and renal failure'''|| ❑ Frequent monitoring and correction of derangements in glucose, potassium, magnesium and phosphate '''(III)'''<br> ❑ Continuous modes of hemodialysis (if needed) '''(I)'''
|'''Drug induced''' ||
* History of hepatotoxic drug intake (usually idiosyncratic hepatotoxic drug intake within first 6 months after drug initiation; continuous usage of potentially hepatotoxic drug for more than 1 to 2 years is unlikely to cause de novo liver damage
* Detailed history taking (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary supplements taken over the past year <br>Determine ingredients of non-prescription medications whenever possible
|
* Discontinue all but essential medications in the setting of possible drug hepatotoxicity.<br>
* NAC (may be beneficial for ALF induced by drugs)  
|-
|-
| '''Hematologic System'''|| '''Coagulopathy'''|| ❑ Replacement therapy for [[thrombocytopenia]] and/or prolonged prothrombin time with platelet and [[FFP]] transfusion respectively in the setting of active bleeding or before invasive procedure '''(III)'''<br> ❑ [[Vitamin K]] (5-10 mg subcutaneously) (at least one dose)<ref name="Pereira-2005">{{Cite journal  | last1 = Pereira | first1 = SP. | last2 = Rowbotham | first2 = D. | last3 = Fitt | first3 = S. | last4 = Shearer | first4 = MJ. | last5 = Wendon | first5 = J. | last6 = Williams | first6 = R. | title = Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease. | journal = J Hepatol | volume = 42 | issue = 3 | pages = 365-70 | month = Mar | year = 2005 | doi = 10.1016/j.jhep.2004.11.030 | PMID = 15710219 }}</ref><br> ❑ Plasmapheresis or recombinant activated factor VII (rFVIIa) in case of inadequate correction of severely elevated INR and risks of volume overload<br> ❑ Maintenance of adequate platelet count
|'''Malignant infiltration''' ||
:In the absence of bleeding: >10,000/mm<sup>3</sup><ref name="Heckman-1997">{{Cite journal  | last1 = Heckman | first1 = KD. | last2 = Weiner | first2 = GJ. | last3 = Davis | first3 = CS. | last4 = Strauss | first4 = RG. | last5 = Jones | first5 = MP. | last6 = Burns | first6 = CP. | title = Randomized study of prophylactic platelet transfusion threshold during induction therapy for adult acute leukemia: 10,000/microL versus 20,000/microL. | journal = J Clin Oncol | volume = 15 | issue = 3 | pages = 1143-9 | month = Mar | year = 1997 | doi =  | PMID = 9060557 }}</ref>
* Massive [[hepatomegaly]]  
:For performing invasive procedures: 50-70,000/ mm<sup>3</sup><br>
❑ Prophylaxis for stress ulceration: '''(I)'''
:❑ I line: [[H2 blocker]] or [[PPI]]
:❑ II line: [[Sucralfate]]
|-
| '''Immunologic System'''|| '''Infection'''|| ❑ Periodic surveillance for prompt initiation of antimicrobial treatment of infections at the earliest sign of active infection or deterioration (progression to high grade hepatic encephalopathy or elements of the [[SIRS]]) '''(III)'''<br> ❑ Antibiotic prophylaxis (possibly helpful in patients with coagulopathy, organ failure, encephalopathy and in whom illness progression is considered likely - not proven) '''(III)'''
|}


{| class="wikitable sortable"
* Malignant infiltration in liver imaging or liver biopsy (confirms or excludes diagnosis)  
!Etiology
|
!Diagnostic Indicators
* Appropriate management of underlying malignancy<br>
!Management Recommendations
* Supportive care
|-
|'''Acetaminophen toxicity''' ||❑ H/o of acetaminophen intake (toxic dose >10 gm/day or >150 mg/kg)<BR>❑ Acetaminophen in blood and/or urine<BR>❑ [[Aminotransferase]] levels >3500 IU/L with low bilirubin levels, in the absence of apparent hypotension or cardiovascular collapse (suspected acetaminophen toxicity in the absence of a positive history because acetaminophen is the leading cause of ALF at least in the United States and Europe)<ref name="Ostapowicz-2002">{{Cite journal  | last1 = Ostapowicz | first1 = G. | last2 = Fontana|first2 = RJ. | last3 = Schiødt | first3 = FV. | last4 = Larson | first4 = A. | last5 = Davern | first5 = TJ. | last6 = Han | first6 = SH. | last7 = McCashland|first7 = TM. | last8 = Shakil | first8 = AO. | last9 = Hay | first9 = JE. | title = Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. | journal = Ann Intern Med | volume = 137 | issue = 12 | pages = 947-54 | month = Dec | year = 2002 | doi =  | PMID = 12484709 }}</ref>||❑'''Activated charcoal:'''<br>1g/kg PO within 1 hour after drug ingestion (may be beneficial even when administered within 3-4 hours after ingestion)<ref name="Sato-2003">{{Cite journal  | last1 = Sato | first1 = RL. | last2 = Wong | first2 = JJ. | last3 = Sumida | first3 = SM. | last4 = Marn | first4 = RY. | last5 = Enoki | first5 = NR. | last6 = Yamamoto | first6 = LG. | title = Efficacy of superactivated charcoal administered late (3 hours) after acetaminophen overdose. | journal = Am J Emerg Med | volume = 21 | issue = 3 | pages = 189-91 | month = May | year = 2003 | doi =  | PMID = 12811710 }}</ref> and prior to starting [[NAC]] '''(I)'''<br>❑ '''[[Nomogram]]''' (helps determining the likelihood of serious liver damage but does not exclude possible toxicity)<br>❑ '''NAC:''' <br>140 mg/kg PO or through NGT (diluted to 5% solution), then 70 mg/kg PO q4h x 17 doses<br>'''or'''<br>IV loading dose of 150 mg/kg in 5% dextrose over 15 minutes, then maintenance dose of 50 mg/kg IV over the next 4 hours and then 100 mg/kg IV over the following 16 hours<br>*Promptly begin NAC (beneficial even when administered <48 hours after drug ingestion) in all patients with impending or evolving liver injury due to acetaminophen '''(II-1)'''<br>*NAC may be used in cases of ALF due to suspected acetaminophen poisoning '''(III)'''<br>*NAC is recommended even in case of non-acetaminophen ALF<ref name="Lee-2009">{{Cite journal  | last1 = Lee | first1 = WM. | last2 = Hynan | first2 = LS. | last3 = Rossaro | first3 = L. | last4 = Fontana | first4 = RJ. | last5 = Stravitz | first5 = RT. | last6 = Larson | first6 = AM. | last7 = Davern | first7 = TJ. | last8 = Murray | first8 = NG. | last9 = McCashland | first9 = T. | title = Intravenous N-acetylcysteine improves transplant-free survival in early stage non-acetaminophen acute liver failure. | journal = Gastroenterology | volume = 137 | issue = 3 | pages = 856-64, 864.e1 | month = Sep | year = 2009 | doi = 10.1053/j.gastro.2009.06.006 | PMID = 19524577 }}</ref>
|-
|'''Acute fatty liver of pregnancy/HELLP''' ||❑ Jaundice and hypertension<br>❑ Coagulopathy<br>❑ Thrombocytopenia<br>❑ Proteinuria<br>❑ Hypoglycemia<br>❑ [[Steatosis]] in liver imaging or biopsy ||❑ Early diagnosis and prompt delivery '''(III)'''<br>❑ Adequate supportive care<br>❑ Consider transplantation for postpartum deterioration '''(III)'''
|-
|'''Acute ischemic injury''' ||❑ H/o cardiac arrest<br>❑ Any period of significant hypovolemia/hypotension, or severe [[CHF]] (hypotension is not documented always)<br>❑ Any associated renal dysfunction & muscle necrosis<br>❑ Elevated aminotransferase levels responding to fluid resuscitation||❑ Adequate cardiovascular support '''(III)'''
|-
|'''Autoimmune''' ||❑ Positive serum autoantibodies (may be absent)<br>❑ Positive liver biopsy (confirms diagnosis when [[autoimmune hepatitis]] is suspected and autoantibodies are negative) '''(III)''' ||❑ [[Prednisolone]] (start with 40-60 mg/day, especially in the presence of coagulopathy and mild hepatic encephalopathy) '''(III)'''<br>❑ Consider transplantation and do not delay while awaiting response to steroid treatment '''(III)'''
|-
|'''Budd-Chiari''' ||❑ Abdominal pain<br>❑ Ascites<br> ❑ Hepatomegaly<br>❑ Blood tests positive for hypercoagulability<br>❑ Positive findings during liver imaging ([[CT]], [[Medical ultrasonography#Doppler sonography|doppler USG]], [[venography]] or magnetic resonance venography) (confirms diagnosis) ||❑ Liver transplantation (provided underlying malignancy is excluded) '''(II-3)'''
|-
|'''Drug induced''' ||❑ H/o hepatotoxic drug intake (usually idiosyncratic hepatotoxic drug intake within first 6 months after drug initiation; continuous usage of potentially hepatotoxic drug for more than 1 to 2 years is unlikely to cause de novo liver damage)<br>❑ H/o inclusive of details (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary supplements taken over the past year '''(III)'''<br>❑ Determine ingredients of non-prescription medications whenever possible '''(III)''' ||❑ Discontinue all but essential medications in the setting of possible drug hepatotoxicity '''(III)'''<br>❑ NAC (may be beneficial for ALF induced by drugs) '''(I)'''
|-
|'''Malignant infiltration''' ||❑ Massive hepatomegaly<br>❑ Malignant infiltration in liver imaging or liver biopsy (confirms or excludes diagnosis) '''(III)'''||❑ Appropriate management of underlying malignancy<br>❑ Supportive care
|-
|'''Mushroom poisoning''' ||❑ H/o recent mushroom intake<br>❑ Severe GI symptoms like nausea, vomiting and diarrhea within hours or a day of ingestion (suspected mushroom poisoning in the absence of a positive history) ||❑ Early gastric lavage and activated charcoal administration<br>❑ [[Penicillin|Penicillin G]] 300,000-1 million units/kg/day<br>'''or'''<br>[[Silibinin]] 30-40 mg/kg/day IV or PO, 3-4 days (silymarin in Europe and south America; milk thistle in north America)<ref name="Enjalbert-2002">{{Cite journal  | last1 = Enjalbert | first1 = F. | last2 = Rapior | first2 = S. | last3 = Nouguier-Soulé | first3 = J. | last4 = Guillon | first4 = S. | last5 = Amouroux | first5 = N. | last6 = Cabot | first6 = C. | title = Treatment of amatoxin poisoning: 20-year retrospective analysis. | journal = J Toxicol Clin Toxicol | volume = 40 | issue = 6 | pages = 715-57 | month =  | year = 2002 | doi =  | PMID = 12475187 }}</ref><br>❑ NAC '''(III)'''<br>❑ Liver transplantation (the only lifesaving option) '''(III)'''<br>❑ Fluid resuscitation (as needed)
|-
|'''Viral''' ||❑ Toxically appearing patients with skin lesions (HSV)<br>❑ Positive hepatitis virus serology<br>❑ [[HSV]] positive liver biopsy ||❑ Supportive treatment (no virus specific treatment proven to be effective) '''(III)'''<BR>❑ Nucleoside and nucleotide analogues (for [[HBV]] associated ALF) '''(III)'''<BR>❑ [[Acyclovir]] (5-10 mg/kg every 8 hours for at least 7 days for HSV or VZV) '''(III)'''
|-
|'''Wilson's disease''' ||❑ KF ring<br>❑ Serum bilirubin >20 mg/dL,<br>❑ Bilirubin:alkaline phosphatase >2.0<br>❑ Low serum ceruloplasmin<br>❑ Elevated serum & urine copper<br>❑ High copper levels in liver biopsy '''(III)'''||❑ Liver transplantation '''(III)'''<br>❑ Dialysis or hemofiltration or plasmapheresis or plasma exchange
|-
|'''Intermediate etiology''' ||❑ Etiology undetermined after all evaluation||❑ Review drug and toxin intake H/o<BR>❑ Transjugular biopsy (for further evaluation of possible mailgnancy, [[Wilson disease]], autoimmune hepatitis and [[viral hepatitis]]) '''(III)'''
|}
</div>
<div class="mw-collapsible mw-collapsed">
====Transplantation====
<div class="mw-collapsible-content">
{| class="wikitable"
! Liver Transplantation!! Recommendations
|-
| Prognostic scoring systems|| Currently available and widely applied prognostic scoring systems (King’s College Hospital criteria-KCH Criteria,<ref name="O'Grady-1989">{{Cite journal  | last1 = O'Grady | first1 = JG. | last2 = Alexander | first2 = GJ. | last3 = Hayllar | first3 = KM. | last4 = Williams | first4 = R. | title = Early indicators of prognosis in fulminant hepatic failure. | journal = Gastroenterology | volume = 97 | issue = 2 | pages = 439-45 | month = Aug | year = 1989 | doi =  | PMID = 2490426 }}</ref> Clichy Criteria,<ref name="Bernuau-1986">{{Cite journal  | last1 = Bernuau | first1 = J. | last2 = Rueff | first2 = B. | last3 = Benhamou | first3 = JP. | title = Fulminant and subfulminant liver failure: definitions and causes. | journal = Semin Liver Dis | volume = 6 | issue = 2 | pages = 97-106 | month = May | year = 1986 | doi = 10.1055/s-2008-1040593 | PMID = 3529410 }}</ref> and Japanese Criteria<ref name="Mochida-2008">{{Cite journal  | last1 = Mochida | first1 = S. | last2 = Nakayama | first2 = N. | last3 = Matsui | first3 = A. | last4 = Nagoshi | first4 = S. | last5 = Fujiwara | first5 = K. | title = Re-evaluation of the Guideline published by the Acute Liver Failure Study Group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis. | journal = Hepatol Res | volume = 38 | issue = 10 | pages = 970-9 | month = Oct | year = 2008 | doi = 10.1111/j.1872-034X.2008.00368.x | PMID = 18462374 }}</ref>) do not adequately predict outcome and determine candidacy for liver transplantation, thus not recommending the entire reliance entirely upon these guidelines '''(III)'''
|-
| Urgent hepatic transplantation|| Urgent hepatic transplantation is indicated when prognostic indicators suggest a high likelihood of death '''(II-3)'''
|-
| In the setting of limited organ supply|| In the setting of limited organ supply, either living donor or auxiliary liver transplantation may be considered.  But its use remains controversial '''(II-3)'''
|-
|Liver support systems|| Currently available liver support systems are not recommended outside clinical trials and their future in management of ALF remains unclear'''(II-1)'''
|-
|}
{| class="wikitable"
! Liver Transplantation!! Recommendations
|-
| Prognostic scoring systems|| Currently available and widely applied prognostic scoring systems (King’s College Hospital criteria-KCH Criteria,<ref name="O'Grady-1989">{{Cite journal  | last1 = O'Grady | first1 = JG. | last2 = Alexander | first2 = GJ. | last3 = Hayllar | first3 = KM. | last4 = Williams | first4 = R. | title = Early indicators of prognosis in fulminant hepatic failure. | journal = Gastroenterology | volume = 97 | issue = 2 | pages = 439-45 | month = Aug | year = 1989 | doi =  | PMID = 2490426 }}</ref> Clichy Criteria,<ref name="Bernuau-1986">{{Cite journal  | last1 = Bernuau | first1 = J. | last2 = Rueff | first2 = B. | last3 = Benhamou | first3 = JP. | title = Fulminant and subfulminant liver failure: definitions and causes. | journal = Semin Liver Dis | volume = 6 | issue = 2 | pages = 97-106 | month = May | year = 1986 | doi = 10.1055/s-2008-1040593 | PMID = 3529410 }}</ref> and Japanese Criteria<ref name="Mochida-2008">{{Cite journal  | last1 = Mochida | first1 = S. | last2 = Nakayama | first2 = N. | last3 = Matsui | first3 = A. | last4 = Nagoshi | first4 = S. | last5 = Fujiwara | first5 = K. | title = Re-evaluation of the Guideline published by the Acute Liver Failure Study Group of Japan in 1996 to determine the indications of liver transplantation in patients with fulminant hepatitis. | journal = Hepatol Res | volume = 38 | issue = 10 | pages = 970-9 | month = Oct | year = 2008 | doi = 10.1111/j.1872-034X.2008.00368.x | PMID = 18462374 }}</ref>) do not adequately predict outcome and determine candidacy for liver transplantation, thus not recommending the entire reliance entirely upon these guidelines '''(III)'''
|-
|-
| Urgent hepatic transplantation|| Urgent hepatic transplantation is indicated when prognostic indicators suggest a high likelihood of death '''(II-3)'''
|'''Mushroom poisoning''' ||
* History of recent mushroom intake<br>
* Severe GI symptoms like [[Nausea and vomiting|nausea]], vomiting and [[diarrhea]] within hours or a day of ingestion (suspected mushroom poisoning in the absence of a positive history)
|
* Early gastric lavage and activated charcoal administration<br>
* [[Penicillin|Penicillin G]] 300,000-1 million units/kg/day<br>'''or'''<br>
* [[Silibinin]] 30-40 mg/kg/day IV or PO, 3-4 days (silymarin in Europe and south America; milk thistle in north America)<ref name="Enjalbert-2002">{{Cite journal  | last1 = Enjalbert | first1 = F. | last2 = Rapior | first2 = S. | last3 = Nouguier-Soulé | first3 = J. | last4 = Guillon | first4 = S. | last5 = Amouroux | first5 = N. | last6 = Cabot | first6 = C. | title = Treatment of amatoxin poisoning: 20-year retrospective analysis. | journal = J Toxicol Clin Toxicol | volume = 40 | issue = 6 | pages = 715-57 | month =  | year = 2002 | doi =  | PMID = 12475187 }}</ref><br>
* NAC <br>
* Liver transplantation (the only lifesaving option) <br>
* Fluid resuscitation (as needed)
|-
|-
| In the setting of limited organ supply|| In the setting of limited organ supply, either living donor or auxiliary liver transplantation may be considered.  But its use remains controversial '''(II-3)'''
|'''Viral''' ||
* Toxically appearing patients with skin lesions (HSV)<br>
* Positive hepatitis virus serology<br>
* [[HSV]] positive liver biopsy
|
* Supportive treatment (no virus specific treatment proven to be effective)
* Nucleoside and nucleotide analogues (for [[HBV]] associated ALF) <BR>
* [[Acyclovir]] (5-10 mg/kg every 8 hours for at least 7 days for HSV or VZV)  
|-
|-
|Liver support systems|| Currently available liver support systems are not recommended outside clinical trials and their future in management of ALF remains unclear'''(II-1)'''
|'''Wilson's disease''' ||
* [[Kayser-Fleischer ring|Kayser- Fleischer rings]] (KF rings)
* Serum [[bilirubin]] >20 mg/dL,<br>
* Bilirubin:alkaline phosphatase >2.0<br>
* Low serum [[ceruloplasmin]]<br>
* Elevated serum & urine [[copper]]<br>
* High copper levels in liver biopsy
|
* Liver transplantation <br>
* [[Dialysis]] or hemofiltration or [[plasmapheresis]] or plasma exchange
|-
|-
|'''Intermediate etiology''' ||
* Etiology undetermined after all evaluation.
|
* Review drug and toxin intake history<BR>
* Transjugular biopsy (for further evaluation of possible mailgnancy, [[Wilson disease]], [[autoimmune hepatitis]] and [[viral hepatitis]])
|}
|}


Latest revision as of 21:19, 18 December 2017

Acute liver failure Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aditya Govindavarjhulla, M.B.B.S. [2] Husnain Shaukat, M.D [3]

Overview

The management of acute liver failure involves resuscitation of the patient with adequate nutrition and optimization of fluid balance, monitoring and treating the complications and providing nutritional support. The patient should be treated in an appropriate setting preferably a center with liver transplantation facility. Infections and sepsis are common occurrences of fulminant liver failure. The high standards of infection control should be practiced to minimize the nosocomial sepsis. The diagnosis of hepatic injury in hyperacute cases can be a challenge as jaundice can be minimal during that period and confusion or agitation may be the dominant findings. In acute liver failure, the sedative medications should be used with caution as they may mask the worsening encephalopathy and the hepatic clearance may be decreased which can aggravate the sedative effect. However, the short-acting benzodiazepines in low dose can be used during agitation. In acute liver failure patients, opioids are avoided as they decrease the seizure threshold. H2 receptor blockers and proton pump inhibitors are indicated to prevent and treat stress gastropathy. In stage 3 and 4 encephalopathy, intubation and mechanical ventilation are indicated. Acetylcysteine is used for acetaminophen poisoning for up to 72 hours after ingestion. It can dramatically improve the outcome if administered within eight hours of acetaminophen ingestion. The patients with acute liver failure may not have a clear history of acetaminophen intake. Therefore, the threshold for administering acetylcysteine should be low and can also be administered in an acute liver failure of unknown etiology. Every effort should be made to seek out the specific cause of acute liver failure since specific treatments are available for some causes of acute liver failure. However, inappropriately prolonged investigations may make surgery impossible because of progression of sepsis and multiorgan failure.

Medical Therapy

  • The management of acute liver failure involves taking care of the patient in an appropriate setting, preferably a center with liver transplantation facility, monitoring and treating the complications and providing nutritional support.[1][2][3][4][5][6]

General measures

Management of complications

Encephalopathy

  • The goal of management is to limit the severity of encephalopathy and reduce the risk of cerebral edema.
  • Grade I can be managed on the floors with adequate skilled nursing staff in a calm atmosphere, as it helps in reducing agitation.
  • Grade II encephalopathy has must be managed in ICU setting.
  • For grades III/IV encephalopathy, intubation, and mechanical ventilation are required for management.
  • Monitoring and management of hemodynamic and renal parameters as well as glucose, electrolytes and acid-base status is also important.

Increased Intracranial Pressure

Infections

  • The use of antimicrobials as a prophylaxis may reduce infections in a few patients with acute liver failure, but has no survival benefit.[7]
  • If prophylaxis is not started, there should be ongoing surveillance for the development of infections.
  • The antibiotics are administered preemptively in patients with organ failure, encephalopathy or coagulopathy and in whom illness progression is considered likely. The high standards of infection control should be practiced to minimize the nosocomial sepsis.

Coagulopathy and Bleeding Complications

  • Coagulopathy constitutes a part of the definition of acute liver failure.
  • If there is no evidence of bleeding and INR is not in the normal range, treating the INR with fluids such as plasma may lead to volume overload and may cause transfusion-related lung injury.
  • Vitamin K should be administered routinely (5- 10 mg SC) as there is a decreased synthesis of clotting factors from the liver tissue.
  • In high-risk procedures or clinically significant bleeding, clotting factor deficiencies should be treated.
  • Bleeding mainly occurs from the capillaries, and is usually from mucosal surfaces of the stomach and lung.
  • The mucosal surfaces of the gastrointestinal tract are the most common source of bleeding. So, the patient should receive stress ulcer prophylaxis with proton pump inhibitors or H2 blocking agents.

Hemodynamic and Metabolic Disturbances

Renal and pulmonary complications

Treatment for the Specific Underlying Cause

Acetaminophen Poisoning

Mushroom Poisoning

  • In mushroom poisoning, the early administration of activated charcoal is recommended as it is associated with improved survival.
  • Aditional therapy include Penicillin G - 300,000 to 1 million units/kg/day

Drug Induced Hepatoxicity

Viral Hepatitis

  • Supportive care
  • Viral hepatitis A (and E) related acute liver failure must be treated with supportive care as no virus specific treatment has proven to be effective.
  • Nucleoside analogs should be considered for hepatitis B associated acute liver failure and for prevention of post transplant recurrence.

Herpes Simplex Hepatitis

Wilson's Disease

Autoimmune Hepatitis

HELLP Syndrome

  • Hepatic rupture or hemorrhage are fatal complications of HELLP syndrome requiring immediate resuscitation and intervention.
  • Early diagnosis of the complications, and delivery of the baby helps in improving the outcome.
  • Transplantation my be considered if there is postpartum deterioration.

Shock Liver

  • Treatment of underlying cause of ischemia in shock liver is very important, and determines the prognosis of the condition.
  • Transplantation is seldom indicated.

Budd-Chiari Syndrome

Etiology Diagnostic Indicators Management Recommendations
Acetaminophen toxicity
  • Activated charcoal:
    1g/kg PO within 1 hour after drug ingestion (may be beneficial even when administered within 3-4 hours after ingestion) and prior to starting N-acetylcystine (NAC) .
  • Nomogram (helps to determine the likelihood of serious liver damage but does not exclude possible toxicity)
  • N-acetylcystine (NAC)
    140 mg/kg PO or through NGT (diluted to 5% solution), then 70 mg/kg PO q4h x 17 doses
    or
    IV loading dose of 150 mg/kg in 5% dextrose over 15 minutes, thethen a maintenance dose 50 mg/kg IV over the next 4 hours and 100 mg/kg IV over the following 16 hours
    *Promptly begin NAC (beneficial even when administered <48 hours after drug ingestion) in all patients with impending or evolving liver injury due to acetaminophen.
Acute fatty liver of pregnancy/HELLP
  • Early diagnosis and prompt delivery.
  • Adequate supportive care.
  • Consider transplantation for postpartum deterioration
Acute ischemic injury
  • History of cardiac arrest
  • Any period of significant hypovolemia/hypotension, or severe CHF (hypotension is not documented always)
  • Any associated renal dysfunction & muscle necrosis
  • Elevated aminotransferase levels responding to fluid resuscitation
  • Adequate cardiovascular support.
Autoimmune
  • Prednisolone (start with 40-60 mg/day, especially in the presence of coagulopathy and mild hepatic encephalopathy)
  • Consider transplantation and do not delay while awaiting response to steroid treatment
Budd-Chiari
  • Liver transplantation (provided underlying malignancy is excluded)
Drug induced
  • History of hepatotoxic drug intake (usually idiosyncratic hepatotoxic drug intake within first 6 months after drug initiation; continuous usage of potentially hepatotoxic drug for more than 1 to 2 years is unlikely to cause de novo liver damage
  • Detailed history taking (including onset of ingestion, amount and timing of last dose) concerning all prescription and non-prescription drugs, herbs and dietary supplements taken over the past year
    Determine ingredients of non-prescription medications whenever possible
  • Discontinue all but essential medications in the setting of possible drug hepatotoxicity.
  • NAC (may be beneficial for ALF induced by drugs)
Malignant infiltration
  • Malignant infiltration in liver imaging or liver biopsy (confirms or excludes diagnosis)
  • Appropriate management of underlying malignancy
  • Supportive care
Mushroom poisoning
  • History of recent mushroom intake
  • Severe GI symptoms like nausea, vomiting and diarrhea within hours or a day of ingestion (suspected mushroom poisoning in the absence of a positive history)
  • Early gastric lavage and activated charcoal administration
  • Penicillin G 300,000-1 million units/kg/day
    or
  • Silibinin 30-40 mg/kg/day IV or PO, 3-4 days (silymarin in Europe and south America; milk thistle in north America)[11]
  • NAC
  • Liver transplantation (the only lifesaving option)
  • Fluid resuscitation (as needed)
Viral
  • Toxically appearing patients with skin lesions (HSV)
  • Positive hepatitis virus serology
  • HSV positive liver biopsy
  • Supportive treatment (no virus specific treatment proven to be effective)
  • Nucleoside and nucleotide analogues (for HBV associated ALF)
  • Acyclovir (5-10 mg/kg every 8 hours for at least 7 days for HSV or VZV)
Wilson's disease
Intermediate etiology
  • Etiology undetermined after all evaluation.

References

  1. ↑ Khadzhidekova VB, Benova DK, Ivanov BA, Mileva MS, Kolev MI (1985). "[Mutagenic effect of the cytostatic drug thaliblastine on rat bone marrow cells when administered alone and in combination with radiation]". Radiobiologiia (in Russian). 25 (5): 656–60. PMID 2933761.
  2. ↑ Larsen FS, Schmidt LE, Bernsmeier C, Rasmussen A, Isoniemi H, Patel VC; et al. (2016). "High-volume plasma exchange in patients with acute liver failure: An open randomised controlled trial". J Hepatol. 64 (1): 69–78. doi:10.1016/j.jhep.2015.08.018. PMID 26325537.
  3. ↑ Demetriou AA, Brown RS, Busuttil RW, Fair J, McGuire BM, Rosenthal P, Am Esch JS, Lerut J, Nyberg SL, Salizzoni M, Fagan EA, de Hemptinne B, Broelsch CE, Muraca M, Salmeron JM, Rabkin JM, Metselaar HJ, Pratt D, De La Mata M, McChesney LP, Everson GT, Lavin PT, Stevens AC, Pitkin Z, Solomon BA (2004). "Prospective, randomized, multicenter, controlled trial of a bioartificial liver in treating acute liver failure". Ann. Surg. 239 (5): 660–7, discussion 667–70. PMC 1356274. PMID 15082970.
  4. ↑ Saliba F, Camus C, Durand F, Mathurin P, Letierce A, Delafosse B; et al. (2013). "Albumin dialysis with a noncell artificial liver support device in patients with acute liver failure: a randomized, controlled trial". Ann Intern Med. 159 (8): 522–31. doi:10.7326/0003-4819-159-8-201310150-00005. PMID 24126646.
  5. ↑ Tritto G, Davies NA, Jalan R (2012). "Liver replacement therapy". Semin Respir Crit Care Med. 33 (1): 70–9. doi:10.1055/s-0032-1301736. PMID 22447262.
  6. ↑ Stutchfield BM, Simpson K, Wigmore SJ (2011). "Systematic review and meta-analysis of survival following extracorporeal liver support". Br J Surg. 98 (5): 623–31. doi:10.1002/bjs.7418. PMID 21462172.
  7. ↑ Vaquero J, Polson J, Chung C, Helenowski I, Schiodt FV, Reisch J, Lee WM, Blei AT (2003). "Infection and the progression of hepatic encephalopathy in acute liver failure". Gastroenterology. 125 (3): 755–64. PMID 12949721. Retrieved 2012-10-26. Unknown parameter |month= ignored (help)
  8. ↑ Czaja AJ (2012). "Acute and Acute Severe (Fulminant) Autoimmune Hepatitis". Digestive Diseases and Sciences. doi:10.1007/s10620-012-2445-4. PMID 23090425. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  9. ↑ Ringe B, Lang H, Oldhafer KJ, Gebel M, Flemming P, Georgii A, Borst HG, Pichlmayr R (1995). "Which is the best surgery for Budd-Chiari syndrome: venous decompression or liver transplantation? A single-center experience with 50 patients". Hepatology (Baltimore, Md.). 21 (5): 1337–44. PMID 7737640. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  10. ↑ Ostapowicz, G.; Fontana, RJ.; Schiødt, FV.; Larson, A.; Davern, TJ.; Han, SH.; McCashland, TM.; Shakil, AO.; Hay, JE. (2002). "Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States". Ann Intern Med. 137 (12): 947–54. PMID 12484709. Unknown parameter |month= ignored (help)
  11. ↑ Enjalbert, F.; Rapior, S.; Nouguier-Soulé, J.; Guillon, S.; Amouroux, N.; Cabot, C. (2002). "Treatment of amatoxin poisoning: 20-year retrospective analysis". J Toxicol Clin Toxicol. 40 (6): 715–57. PMID 12475187.

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