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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—most common cause

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

                        Thiazolidinediones, herbal remedies

            Hepatotropic viruses

                        Hepatitis A—rare, usually good prognosis

Hepatitis B—most common viral cause

Hepatitis C—rare cause in Western countries

                        Hepatitis D—requires co-infection with HBV

                        Hepatitis E—rare

                        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

                        Wilson’s disease

                        Other infections--EBV, herpesviruses, tuberculosis

                        Vascular abnormalities—Budd Chiari syndrome, hepatic veno-occlusive

                                    Disease

Toxins—Amanita phalloides ingestion, sea anemone sting, carbon

            tetrachloride

                        Fatty liver of pregnancy

                        Autoimmune hepatitis

                        Malignant infiltration—lymphoma, melanoma, breast cancer

                        Ischemia—hypotension, heat stroke

                        Reye’s syndrome

                        Primary graft non-function following liver transplantation

 

Clinical Presentation

Nonspecific complaints—nausea, vomiting, fatigue, malaise, followed by

            Jaundice

 

Complications of ALF

            Encephalophathy

                        Stage 1—change in affect, insomnia, difficulty with concentration

                        Stage 2—drowsiness, disorientation, confusion

                        Stage 3—marked somnolence, incoherence

                        Stage 4—frank coma

            Seizures

Cerebral edema—associated with stage 3 and stage 4 encephalopathy

Hypoglycemia

Coagulopathy—GI bleed, mucosal sites, vascular puncture sites

                        INR and PT correlate with severity of liver

            Infection—impaired 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 toxicity—N-acetylcysteine

            Herpes-induced fulminant hepatitis—IV acyclovir

            Fatty liver of pregnancy—emergency delivery

            Autoimmune  hepatitis—glucocorticoid

            Amanita phalloides ingestion—penicillin 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, LFT’s, PT, PTT, INR every 6 – 8 hours

Correct electrolytes

Coags are utilized to assess prognosis—No 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 monitoring—consider 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

 

 

 

 

 

King’s College Hospital Criteria for Liver Transplantation

Acetaminophen-Induced FHF

Arterial pH <7.3(irrespective of grade of encephalopathy)

OR

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)

OR

Presence of any 3 of the following:

                        Age <10yrs or >40yrs

Non-A, non-B hepatitis, halothane, idiosyncratic drug reaction, Wilson’s

            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 & Fordtran’s 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

 

 

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