Guidelines for Management of Acute Liver Failure/Fulminant Hepatic Failure

by M. Njoku, MD

Dept of Anesthesia

University of Maryland Medical System

Criteria for definition

1)rapid development of hepatocellular dysfunction(ex. jaundice, coagulopathy)

2)encephalopathy within 8 weeks of onset of jaundice

3)absence of prior history of liver disease

Causes

Drugs are the most common cause

Acetominophen, halothane, isoniazid, valproate, sulfonamides, phenytoin,

Thiazolidinediones, herbal remedies

Hepatotropic viruses

Hepatitis Arare, usually good prognosis

Hepatitis Bmost common viral cause

Hepatitis Crare cause in Western countries

Hepatitis Drequires co-infection with HBV

Hepatitis Erare

Togavirus, transfusion transmitted virus, parvovirus B19

Unknown Etiololgy/Cryptogenic

Defined by negative serologic testing for HAV, HBV and absence of other known causes

Uncommon Causes

Wilsons disease

Other infections–EBV, herpesviruses, tuberculosis

Vascular abnormalitiesBudd Chiari syndrome, hepatic veno-occlusive

Disease

ToxinsAmanita phalloides ingestion, sea anemone sting, carbon

tetrachloride

Fatty liver of pregnancy

Autoimmune hepatitis

Malignant infiltrationlymphoma, melanoma, breast cancer

Ischemiahypotension, heat stroke

Reyes syndrome

Primary graft non-function following liver transplantation

Clinical Presentation

Nonspecific complaintsnausea, vomiting, fatigue, malaise, followed by

Jaundice

Complications of ALF

Encephalophathy

Stage 1change in affect, insomnia, difficulty with concentration

Stage 2drowsiness, disorientation, confusion

Stage 3marked somnolence, incoherence

Stage 4frank coma

Seizures

Cerebral edemaassociated with stage 3 and stage 4 encephalopathy

Hypoglycemia

CoagulopathyGI bleed, mucosal sites, vascular puncture sites

INR and PT correlate with severity of liver

Infectionimpaired immune function, nosocomial sources

Multiple organ failure syndrome

Management and Workup

Attempt to identify the cause

History, Physical exam

Toxicology Screen

Viral serology

Hep A IgM Ab, Hep A(IgG IgM) Anti-HAV, Hep B surface Ab, Hep B surface Ab quant, Hep B surface Ag, Hep C Ab screen, Hep C PCR, HSV IgG, HSV IgM, EBV IgG, EBV IgM, Rubella IgG screen, Varicella IgG

Rapid Tests

Hep A IgM Ab, HepBsurface Ag, Hep Bcore IgM Ab, HIV, CMV IgM,

CMV IgG

Autoimmune serology

Anti-nuclear antibody and titer, Ribonucleic protein antibody, Smith antibody, smooth muscle antibody, SS-A(Ro) antibody, SS-B(La), antibodies to liver-kidney-microsome type 1

Other Lab Tests

Alpha-1 antitrypsin, ceruloplasmin, alpha feto protein, HIV-1/HIV-2,

CMV IgG, CMV IgM, TSH, HCG

RUQ Ultrasound to assess vessel patency

CT/MRI

Consider transjugular liver biopsy

Etiology-specific Treatment(if indicated)

Acetaminophen toxicityN-acetylcysteine

Herpes-induced fulminant hepatitisIV acyclovir

Fatty liver of pregnancyemergency delivery

Autoimmune hepatitisglucocorticoid

Amanita phalloides ingestionpenicillin and silibinin

Early evaluation of candidacy for liver transplantation and referral to a transplant center

Immediately Consult

Hepatologist

Liver Transplant Surgeon

Transplant Anesthesiologist

Intensive medical management until spontaneous recovery, hepatic regeneration or liver transplantation

Measure electrolytes, ionized calcium, magnesium, phosphorus, BUN, creatinine,

glucose, ammonia, arterial lactate, LFTs, PT, PTT, INR every 6 8 hours

Correct electrolytes

Coags are utilized to assess prognosisNo need to correct coags in a patient who

is not bleeding

If serum glucose < 70

administer glucose in IVF

consider D50 bolus, D5 ½ NS, D5NS or D10/D20 + a balanced salt solution titrate glucose solution for FS 70 80

continue to monitor fingerstick q 1 2 hours

Neuro Exam q 1 hour

Report any worsening of neuro exam, lateralizing signs, posturing, or

seizures to house officer and transplant team

No sedatives, analgesics, or neuroleptics because of effect on neuro exam

Look for other causes of alteration in neuro exam

Electrolytes, glucose, acid-base, ventilation, oxygenation, subclinical seizures

Head CT for any worsening of neuro exam

Evaluate for edema, mass lesion, hemorrhage, brain stem herniation

Anticipate Intubation for airway protection and mechanical ventilation for

stage 3 or 4 encephalopaty

ICP monitoringconsider for stage 3 encephalopathy, usually required

for stage 4 encephalopathy

Consult Neurosurgery for epidural pressure monitor or subdural(Camino) catheter

Correct coags for epidural pressure monitor placement

Monitor for volume overload, may need diuresis

Decrease in IV fluids to accommodate FFP load

Consider Factor VII, instead of FFP, if fluid overload

(requires pharmacy/physician approval)

Coordinate optimal time of coag correction with

neurosurgery and OR team

Repeat Head CT following epidural pressure monitor placement

Consider measurement CMR or JvO2 or TCD

Treatment of Intracranial Hypertension(ICP > 15)

Maintain CPP 60 100(CPP = MAP ICP)

If CPP is low and MAP is low

optimize volume status, then consider inotrope

If CPP is low and ICP is elevated

utilize measures below:

Head elevation > 20o 30o, midline position

Intubation, Mild Hyperventilation, Normoxia

Active cooling, if febrile

Mannitol, if renal function intact, 0.5 mg/kg

monitor serum osmolarity and serum sodium q6h

withold mannitol for serum Na > 150 and serum Osm >320

Barbiturates¯CBV, ¯ICP, treat and prevent seizures

Titrate barbs to ICP £ 15 and CPP 60 100

If seizures present use EEG to confirm suppression

NOTE: The mechanism of death is cerebral edema and herniation if there is no spontaneous recovery or transplant

Lactulose (po), 30 cc bid to qid, for 4 5 stools per day

or Metronidazole(po) 250 mg qid

Enteral Nutrition, 35 50kcal/kg/d + protein 1gm/kg/d

DVT prophylaxis/pneumatic compression stockings

Coagulopathy includes inability to synthesize protein C, protein S, ATIII and a pro-coagulant state

Vitamin K 10mg IV q day x 3 days, for suspected deficiency

Stress ulcer prophylaxis

Monitor for signs and treat bacterial or other nosocomial infection

Invasive monitoring(CVP or PAC and arterial line as indicated) to guide

intravascular volume replacement and hemodynamics

Renal dysfunction

Correct volume deficits, electrolytes, acid-base abnormalities

Discontinue nephrotoxic agents

Rule out obstructive uropathy, parenchymal renal disease, UTI

Check urine microscopy, urine electrolytes, calculate FENa

Bicarbonate or tromethamine to correct acid base abnormalities depending

On serum sodium

Consider CVVHD for ARF unresponsive to other medical measures

Indicated for uncontrolled acidosis, hyperkalemia, fluid overload, management of cerebral edema with concomitant renal failure

Respiratory Dysfunction

Aspiration risk with progressive obtundation

Nosocomial pulmonary infection risk is increased

ARDS is associated with ALF and FHF

Consider intubation for airway protection as neuro exam worsens

Consider intubation to facilitate pulmonary toilet and improve gas

exchange

Obtain baseline EKG, CXR

Tissue and blood type

Kings College Hospital Criteria for Liver Transplantation

Acetaminophen-Induced FHF

Arterial pH <7.3(irrespective of grade of encephalopathy)

Presence of all 3 of the following:

PT >100secs(INR > 6.5)

Grade III – IV encephalopathy

Serum creatinine >3.4 mg/dL

Non-Acetaminophen-Induced FHF

PT > 100secs(INR > 6.5)(irrespective of grade of encephalopathy)

Presence of any 3 of the following:

Age <10yrs or >40yrs

Non-A, non-B hepatitis, halothane, idiosyncratic drug reaction, Wilsons

disease

Serum bilirubin > 17.5 mg/dL

Jaundice to encephalopathy time of greater than 7 days

PT > 50secs(INR > 3.5)

Contraindications for Liver Transplantation

Extrahepatic malignancy

Uncontrolled extrahepatic sepsis

Irreversible brain injury caused by intracranial hemorrhage

Unresponsive cerebral edema,

CPP < 40 for 2 hours or more

Persistent ICP > 40 mm Hg

Advanced cardiopulmonary disease

Active substance abuse

References:

Yee HF, Lidofsky SD. Acute Liver Failure. In: Feldman: Sleisenger & Fordtrans Gastrointestinal and Liver Disease, 7th edition, Philadelphia: Elsevier Science; 2002:

567 1576.

Krasko A, Deshpande K, Bonvino S. Liver failure, transplantation, and critical care. Critical Care Clinics 2003 April Apr;19(2).

Sanyal AJ, Stravitz RT. Acute Liver Failure. In: Zakim D, Boyer T, editors. Hepatology: A Textbook of Liver Disease. Philadelphia: Elsevier Science: 2003: 445 496.

Wendon J, Williams R. Transplantation for Fulminant Hepatic Failure. In: Busuttil RW, Klintmalm GB, editors. Tranplantation of the Liver. Philadephia: Saunders: 1996: 93 100.

Appendix

N-Acetylcysteine

Confirm hepatotoxic ingestion

7.5 gm, adult

150 mg/kg, child

Measure blood level at least 4 hours following ingestion

Correlate level with acetaminophen toxicity nomogram

Treatment may be beneficial up to 36 hours following ingestion

If treatment indicated, use the following guidelines

N-Acetylcysteine(po)

140 mg/kg followed by 17 additional doses of 70mg/kg every 4h

N-Acetylcysteine(IV)

Loading dose

150 mg/kg in 200ml 5% dextrose, infused over 15 minutes,

Maintenance dose

50 mg/kg in 500ml of 5% dextrose, infused over 4 hours,

followed by

100 mg/kg in 1000ml of 5% dextrose infused over 16 hours

Treatment for Amanita phalloides poisoning

Penicillin G 1gram/kg/d or 1.8 million U/ kg/d IV

And

Silibinin 20- 50 mg/kg/d IV

Recombinant Factor VIIa

100 mcg/kg IV rounded to nearest vial size, single dose

t1/2 2.3 hours

measure PT, PTT 1 hour following dose

Prednisone, Single Drug Therapy for Autoimmune Hepatitis

60mg/day x 1week, then

40mg/day x 1week, then

30mg/day x 2weeks, then

20mg/day until end point(remission, treatment failure, incomplete response, or drug toxicity)

Pentobarbital

Administration guidelines attached

Acyclovir for HSV

5 10 mg/kg every 8 hours, for 7 10 days