Medical Care: The most important step is to identify the cause of liver failure. Prognosis of ALF is dependent on etiology. A few etiologies of ALF demand immediate and specific treatment. It is also critical to identify those patients who will be candidates for liver transplant.
The most important aspect of treatment is to provide good intensive care support. Patients with grade II encephalopathy should be transferred to ICU for monitoring. As the patient develops progressive encephalopathy, protection of the airway is important. Most patients with ALF tend to develop some degree of circulatory dysfunction. Careful attention should be paid to fluid management, hemodynamics, metabolic parameters, and surveillance of infection. Maintenance of nutrition and prompt recognition of gastrointestinal bleeding are crucial. Coagulation parameters, complete blood count, and metabolic panel should be checked frequently. Serum aminotransferases and bilirubin are generally measured daily to follow the course of infection. Intensive care management includes recognition and management of complications.
Airway protection
As the patients with FHF drift deeper into coma, their ability to protect their airway from aspiration decreases. Patients who are in stage III coma should have a nasogastric tube for stomach decompression. When patients progress to stage III coma, the intubation should be performed.
Short-acting benzodiazepines in low doses (eg, midazolam 2-3 mg) may be used prior to intubation or propofol (50 mcg/kg/min) may be initiated before intubation and continued as an infusion. It is also known to decrease the cerebral blood flow and intracranial hypertension. It may be advisable to use endotracheal lidocaine prior to endotracheal suctioning.
Encephalopathy and cerebral edema
Patients with grade I encephalopathy may sometimes be safely managed on a medicine ward. Frequent mental status checks should be performed with transfer to an ICU warranted with progression to grade II encephalopathy.
Head imaging with computerized tomography (CT) is used to exclude other causes of decline in mental status, such as intracranial hemorrhage.
Sedation should be avoided if possible; unmanageable agitation may be treated with short-acting benzodiazepines in low doses.
Patients should be positioned with the head elevated at 30°.
Efforts should be made to avoid patient stimulation. Maneuvers that cause straining or, in particular, Valsalva-like movements may increase ICP.
There is increasing evidence that ammonia may play a pathogenic role in the development of cerebral edema. Reducing elevated ammonia levels with enteral administration of lactulose might help prevent or treat cerebral edema.
ICP monitoring helps in the early recognition of cerebral edema. The clinical signs of elevated ICP, including hypertension, bradycardia, and irregular respirations (Cushing triad), are not uniformly present; these and other neurological changes, such as pupillary dilatation or signs of decerebration, are typically evident only late in the course.
CT of the brain does not reliably demonstrate evidence of edema, especially at early stages. A primary purpose of ICP monitoring is to detect elevations in ICP and reductions in cerebral perfusion pressure (CPP; calculated as mean arterial pressure minus ICP) so that interventions can be made to prevent herniation while preserving brain perfusion.
The ultimate goal of such measures is to maintain neurological integrity and prolong survival while awaiting receipt of a donor organ or recovery of sufficient functioning hepatocyte mass. Additionally, refractory ICH and/or decreased CPP is considered a contraindication to liver transplantation in many centers.
Cardiovascular monitoring
Homodynamic derangements consistent with multiple organ failure occur in ALF. Hypotension (systolic, <80 mm Hg) may be present in 15% of patients. Most patients will require fluid resuscitation on admission. Intravascular volume deficits may be present on admission due to decreased oral intake or GI blood loss. Homodynamic derangement resembles that of sepsis or cirrhosis with hepatorenal syndrome (low SVR with normal or increased cardiac output). An arterial line should be placed for continuous blood pressure monitoring.
A Swan–Ganz catheter should be placed and fluid replacement with colloid albumin should be guided by filling pressure. If needed, dopamine or norepinephrine can be used to correct hypotension.
Management of renal failure: Hemodialysis may significantly lower the mean arterial pressure such that cerebral perfusion pressure is compromised. Continuous veno-venous hemofiltration is preferred.
Management of coagulopathy
In the absence of bleeding, it is not necessary to correct clotting abnormalities with fresh frozen plasma (FFP); the exception is when an invasive procedure is planned or with profound coagulopathy (INR >7). (PT and PTT become prolonged when plasma coagulation components are diluted to less than 30%, and abnormal bleeding occurs when they are less than 17%. One unit of FFP increases the coagulation factor by 5%; 2 units increases it by 10%.) FFP of 15 mL/kg of body weight or 4 units correct deficiency. If fibrinogen is very low (<80 mg/dL), consider cryoprecipitation.
Recombinant factor VII A may be used in patients nonresponsive to FFP. It is used in a dose of 4 µg/kg IV push over 2-5 minutes. PT is normalized in 20 minutes and remains normalized for 3-4 hours.
Platelet transfusions are not used until the count is less than 10,000/µL or if an invasive procedure is being done and the platelet count is less than 50,000/µL. Six to 8 random donor platelets (1 random donor unit platelet/10 kg) will increase the platelet count to greater than 50,000/µL. The platelet count should be checked after 1 hour and 24 hours. Transfused platelets survive 3-5 days.
Managing poisonings (eg, acetaminophen, mushroom) requires specific treatment distinct from other, more general issues related to FHF.
Treat acetaminophen (paracetamol, APAP) overdose with NAC. Researchers theorize that this antidote works by a number of protective mechanisms. Early after overdose, NAC prevents the formation and accumulation of NAPQI, a free radical that binds to intracellular proteins, nonspecifically resulting in toxicity.
NAC increases glutathione stores, combines directly with NAPQI as a glutathione substitute, and enhances sulfate conjugation. NAC also functions as an anti-inflammatory and antioxidant and has positive inotropic and vasodilating effects, which improve microcirculatory blood flow and oxygen delivery to tissues. These latter effects decrease morbidity and mortality once hepatotoxicity is well established.
The protective effect of NAC is greatest when administered within 8 hours of ingestion; however, when indicated, administer regardless of the time since overdose. Therapy with NAC has been shown to decrease mortality in late-presenting patients with FHF (in the absence of acetaminophen in the serum).
A phalloides mushroom intoxication is much more common in Europe as well as in California. Treat with intravenous penicillin G, even though its mode of action is unclear. Silibinin, a water-soluble derivative of silymarin, may be administered orally, and oral charcoal may be helpful by binding the mushroom toxin.
Surgical Care: Liver transplantation is the definitive treatment, but a detailed discussion is beyond the scope of this article. Preoperative management is emphasized here.
In selected patients for whom no allograft is immediately available, consider support with a bioartificial liver. This is a short-term measure that only leads to survival if the liver spontaneously recovers or is replaced.
In the future, hepatocyte transplantation may provide long-term support, but it remains investigational. It has shown dramatic results in animal models of ALF.
Artificial liver support systems
Artificial liver support systems can be divided into 2 major categories: biologic (bioartificial) and nonbiologic.
The bioartificial liver is composed of a dialysis cartridge with mammalian or porcine hepatocytes filling the extra capillary spaces. These devices have undergone controlled trials. One recent multicenter trial did report improved short-term survival for a subgroup of patients with ALF who were treated with a porcine hepatocyte based artificial liver.
Nonbiologic extracorporeal liver support systems, such as hemodialysis, hemofiltration, charcoal hemoperfusion, plasmapheresis, and exchange transfusions, have been used; however, no controlled study has shown long-term benefit.
These modalities permit temporary liver support until a suitable donor liver is found. Although extracorporeal hemoperfusion of charcoal and other inert substances provide some measure of excretory function, no synthetic capacity is provided.
Among the liver support systems currently available, albumin dialysis using the molecular adsorbent recirculating system (MARS) is the one that has been most extensively investigated. In this device, blood is dialyzed across an albumin-impregnated membrane against 20% albumin. Charcoal and anion exchange resins columns in the circuit cleanse and regenerate the albumin dialysate. Clinical studies have shown that it improves hyperbilirubinemia and encephalopathy.
Two other systems based on the removal of albumin bound toxins, the Prometheus using the principle of fractionated plasma separation and adsorption (FPSA) and the single pass albumin dialysis (SPAD), are also undergoing clinical studies for ALF.
Currently available liver support systems are not routinely recommended outside of clinical trials.
Diet:
Patients are, by necessity, nothing by mouth (NPO). They may require large amounts of intravenous glucose to avoid hypoglycemia.
When enteral feeding via a feeding tube is not feasible (eg, as in a patient with paralytic ileus), institute total parenteral nutrition (TPN).
Restricting protein (amino acids) to 0.6 g/kg body weight per day was previously routine in the setting of hepatic encephalopathy, but this may not be necessary.
Activity: Recommend bedrest.
DRUG TREATMENT :
Multiple medications may be necessary because of the wide variety of complications that may develop from FHF. Decreased hepatic metabolism and potential for hepatotoxicity become central issues. Antidotes that effectively bind or eliminate A phalloides toxin and toxic metabolites of acetaminophen are essential.
Acetaminophen ingestion of more than 10 g may be hepatotoxic due to formation of a highly reactive toxic intermediate metabolite, which ordinarily is metabolized further in the presence of glutathione to N-acetyl-p-aminophenol-mercaptopurate. Administering NAC permits restitution of intrahepatic glutathione. It is most effective when administered within 12-20 hours following overdose. Never administer aminoglycosides and NSAIDs because the potential for nephrotoxicity is exaggerated greatly in this setting.
1. PENICILLIN G
2. SILIBININ (Silibinin Plus) -- Water-soluble derivative of silymarin, which is active ingredient in herbal preparation milk thistle. Possesses antioxidant properties that may benefit liver disease management.
DOSE - 20 TO 50 MG /KG/DAY
3. CHARCOAL
4. L-ORNITHINE L-ASPARTATE : INJ LIVOGARD
5. N-ACETYLCYSTEINE( FLUIMUCIL ) -- First DOC. Provides reducing equivalents to help restore depleted intrahepatic glutathione levels.
LOADING DOSE 140 MG / KG FOUR HRLY ORALLY FOR THE TOTAL OF 17 MAINTENANCE DOSES