Varying degrees of hepatic dysfunction, with a variety of causes, are seen in the surgical patient admitted to the critical care unit. There is usually evidence of cholestasis, hepatocellular injury, or a combination of both. Cholestasis is associated with elevation of serum alkaline phosphatase levels and conjugated bilirubin, while hepatocellular damage results in enzyme elevation and increased prothrombin time. Extrahepatic cholestasis should be excluded by ultrasonography of the gallbladder and biliary tree.

(1)total parenteral nutrition

(2)hepatic hypoperfusion

(3)drug induced causes

(4)hepatitis

Elevation of the liver enzymes (aspartate aminotransferase), alkaline phosphatase, and serum bilirubin, is often seen 2 to 6 days after the start of intravenous nutrition. Ultrasonography may be required to exclude extrahepatic obstruction. The underlying aetiology is unclear, but histologically examination shows elements of fatty infiltration as well as periportal inflammation and intrahepatic cholestasis. Secondary bacterial colonization of the biliary tract may also play a role. Biochemical abnormalities can be quite marked, but the clinical course is generally benign. Transition to enteral feeding is associated with resolution of the biochemical and pathological abnormalities.

Hypoperfusion of the liver due to sepsis syndrome, cardiogenic shock, haemorrhagic shock, burns, or trauma can result in mild to severe hepatic dysfunction, depending upon the severity and prolongation of the ischaemic insult. Elements of intrahepatic cholestasis may be present in patients with sepsis syndrome, although the major liver injury is probably a consequence of hypoperfusion associated with endotoxaemia.

A wide range of drugs may be associated with intrahepatic cholestasis, hepatitis, or even massive necrosis. These include erythromycin, chlorpromazine, tolbutamide, and the anabolic steroids (cholestatic) isoniazid, methyldopa, nitrofurantoin (hepatitis-like), carbon tetrachloride, and acetominophen (massive necrosis).

A, B, or non-A, non-B hepatitis should be considered in any patient developing jaundice and the biochemical features of hepatitis. Serological screening and blood precautions should be undertaken.

Hepatic failure that develops acutely over a period of several days or weeks without pre-existing liver disease is referred to as fulminant hepatic failure. It is due to sudden, massive necrosis of hepatocytes, and is followed rapidly by the onset of encephalopathy. In the critical care unit, the likely cause is either viral hepatitis or an overdose of acetaminophen (paracetamol).

Viral hepatitis accounts for up to 70 per cent of cases of acute hepatic failure. The most common causative agent is hepatitis B virus, reported to be responsible for 25 to 75 per cent of cases of viral hepatitis. Hepatitis A is somewhat less common, while non-A, non-B hepatitis accounts for about 30 per cent of cases. Non-A, non-B hepatitis usually follows a slightly slower, but still progressive, course and carries a high mortality—more than 80 per cent. Hepatitis C (non-A, non-B hepatitis group) is often found in association with hepatitis B and is now recognized as major cause of chronic progressive liver disease. The association of hepatitis D (delta agent) with hepatitis B is a serious finding and is usually followed by a rapid deterioration in liver function.

Drug reactions and overdose with acetaminophen (paracetamol) account for about 20 per cent of cases of acute liver failure. Other drugs, such as non-steroidal anti-inflammatory agents and antidepressants, are associated with lesser degrees of liver dysfunction but can cause acute liver failure. Halothane anaesthesia is often proposed as a cause of drug-induced hepatic failure, but increased awareness of this and the avoidance of repeated halothane anaesthesia have greatly reduced this problem. Drug overdose explains about 10 per cent of cases of acute hepatic failure, the most common agents being acetaminophen and ferrous sulphate.

Fulminant hepatic failure is a common feature of Amanita phalloides poisoning: ingestion of 50 g of the mushroom is frequently fatal. Other toxins, such as carbon tetrachloride, methylbromide, chloroform, and xylene may occasionally produce acute hepatic failure. Rare causes of fulminant hepatic failure include profound hypovolaemic shock, Budd–Chiari syndrome, fatty liver of pregnancy, Reye's syndrome, Wilson's disease, and hyperthermia.

Jaundice and fetor hepaticus may often be apparent, while other characteristic signs of liver dysfunction, such as spider naevi, ascites, and liver palms, are generally absent. The serum levels of bilirubin and transaminases are usually elevated, although some patients progress to coma before bilirubin levels become significantly elevated.

Hepatic encephalopathy is usually attributed to neurotoxic materials such as ammonia and mercaptans, derived from the metabolism of nitrogenous compounds in the bowel. These compounds enter the systemic circulation having bypassed the liver through anatomic or functional shunts. Entry of aromatic amino acids into the central nervous system may also account for neurological disturbances. The severity of hepatic encephalopathy can be classified into the four stages shown in Table 1 79.

Most patients with stage IV coma have intracranial pressures raised to more than 30 mmHg. Factors that may precipitate or be associated with hepatic encephalopathy include the administration of sedative or hepatotoxic drugs, bleeding into the gastrointestinal tract, increased dietary protein, and diuretic-induced hypokalaemic alkalosis.

Haemorrhagic manifestations result from decreased synthesis of clotting factors II, V, VII, IX, and X, disseminated intravascular coagulation, and splenic sequestration of platelets. Active bleeding from varices, gastritis, and peptic ulcers further deplete clotting factors, and these should be managed aggressively by replenishing clotting factors with fresh frozen plasma and undertaking surgical or endoscopic intervention if necessary.

Renal failure may complicate hepatic failure for several reasons. Gastrointestinal haemorrhage or overuse of diuretics may result in prerenal azotaemia. Severe or prolonged hypotension, sometimes in association with use of nephrotoxic drugs, may result in vasomotor nephritis (acute tubular necrosis). A serious complication of hepatic failure is the hepatorenal syndrome, a poorly understood condition that results in functional renal failure without clear histopathological lesions in the kidneys: normal renal function returns only if the liver function recovers.

Nosocomial infection occurs in up to 30 per cent of patients and is a common cause of death. There may be a qualitative defect in immune defences due to impaired reticuloendothelial cell clearance, and abnormal leucocyte migration and complement-dependent opsonization.

The adult respiratory distress syndrome is common in patients with end-stage liver failure and is almost uniformly fatal. Impaired clearance of vasoactive substances by the hepatic reticuloendothelial system may contribute to the development of acute lung injury.

Spontaneous bacterial peritonitis should always be suspected in the patient with ascites: this may occur in the absence of peritonism, leucocytosis, or fever. A diagnostic abdominal paracentesis is essential.

Hypoglycaemia may develop because of reduce hepatic glycogen reserves and decreased gluconeogenesis.

The treatment of hepatic encephalopathy includes reducing the gastrointestinal protein load by restricting dietary protein intake, preventing gastrointestinal bleeding, and encouraging intestinal emptying with agents such as lactulose. In stage I and II encephalopathy, protein intake should be restricted to less than 40 g per day, and this should be further reduced to less than 20 g per day in patients with stages III and IV encephalopathy. Caloric intake, preferably as dextrose, should be maintained in excess of 2000 calories per day. Patients with liver damage may be lipid intolerant, and the presence of lipaemic serum requires a reduction of lipid intake. Increased levels of aromatic amino acids (tryptophan, tyrosine, and phenylalanine) may result in decreased synthesis of normal neurotransmitters and, therefore, enhanced synthesis of false neurotransmitters. Such false transmitters may contribute to encephalopathy, although this process might be reversed by the administration of branched-chain amino acids. Neomycin, 0.5 to 1 g administered orally every 6 h, suppresses ammonia production by colonic bacteria. The addition of lactulose, initially in doses of 50 ml orally every 2 h, acts as an osmotic laxative and decreases ammonia absorption from the intestinal lumen by increasing gut intraluminal acidity.

If there is evidence of cerebral oedema, mannitol may be given. There is no evidence that corticosteroids such as dexamethasone have any beneficial effect upon cerebral oedema in this setting or upon the underlying hepatic failure.

Fluid and electrolyte balance requires continuous and meticulous attention. Patients with hepatic failure are generally intolerant of sodium loads and hypokalaemia is poorly tolerated. Volume depletion must be avoided to minimize the risk of vasomotor nephropathy and central venous pressure monitoring is almost obligatory. Target central venous pressures of 8 to 12 mmHg will generally ensure adequate preload. Lower pressures, especially in patients receiving assisted ventilation, carry the risk of volume depletion. If oliguria develops the differential diagnosis includes prerenal azotaemia and the hepatorenal syndrome. Both conditions are associated with a low fractional excretion of sodium (FE&subN;&suba;) so that exclusion of volume depletion is critical to clinical management.

Haemodialysis or haemofiltration should be performed in patients with renal failure if recovery is expected or liver transplantation envisaged. It may be difficult to distinguish between hepatorenal syndrome and vasomotor nephropathy. If doubt exists over the precise cause of renal failure an active approach to management with haemofiltration is indicated.

Use of all types of sedation should be minimized as far as possible. If the use of sedatives cannot be avoided, continuous infusion of a short acting benzodiazepine such as midazolam is acceptable, provided the infusion is discontinued intermittently to reassess the need for sedation. Coexistent renal failure further reduces the clearance of a wide range of medication and lactate.

Coagulopathy is assessed by daily monitoring of the prothombin time. Although there may be little response to the administration of vitamin K, this should be given empirically in doses of 10 mg intravenously daily for 3 days. Vitamin K stores may be severely depleted in the presence of liver necrosis, and supplementation ensures that vitamin K is available if there is any hepatocellular regeneration.

Fresh frozen plasma should be given to patients with severe bleeding or as prophylaxis before an invasive procedure. A target prothrombin time of less than one and a half times control is required for most surgical procedures. Clotting factor concentrates should be avoided since they may precipitate disseminated intravascular coagulation; this is otherwise uncommon unless there is associated sepsis. The most common site of bleeding is the gastrointestinal tract. Bleeding from sites other than surgical wounds, is somewhat infrequent.

Hypoglycaemia should be expected in all patients with fulminant hepatic failure. In the encephalopathic patient the symptoms of hypoglycaemia may not be apparent and hypoglycaemia will only be detected by regular monitoring of blood sugar levels. Dextrose should be administered intravenously as intermittent boluses, or as a continuous infusion if necessary. Administration of glucagon is inappropriate in patients with depleted glycogen stores.

Death secondary to acute hepatic failure usually results from cerebral oedema, sepsis, or haemorrhage. Mortality is related to the stage of encephalopathy (Table 1) 79. Those patients who survive fulminant hepatic failure have a high probability of complete recovery as the liver regenerates over the following 3 to 4 months.

The hepatorenal syndrome refers to renal failure of unknown aetiology which occurs in a fully hydrated patient with severe, often progressive, liver disease. Urine biochemistry is characteristic and renal histopathology is unremarkable. The pathogenesis of the hepatorenal syndrome appears to involve intense intrarenal vasoconstriction and alteration in renal cortical blood flow, possibly due to an imbalance of prostaglandins and thromboxane. Less than 5 per cent of patients with the hepatorenal syndrome survive unless they undergo successful orthotopic liver transplantation. Renal failure is reversed after liver transplantation suggesting that it is due to circulating or systemic factors. Excessive use of diuretics, sepsis, abdominal paracentesis, and gastrointestinal haemorrhage are associated with an increased risk of the hepatorenal syndrome.

Typically, patients who develop the hepatorenal syndrome have signs of advanced liver disease, such as icterus, ascites, palmar erythema, spider angiomata, and hepatic encephalopathy. Laboratory findings confirm hepatic failure, with elevated serum levels of bilirubin, liver enzymes, and ammonia. The impaired synthetic function of the liver usually results in hypoalbuminaemia and prolongation of the prothrombin time. Hyponatraemia, hypokalaemia, and alkalosis are common accompaniments. Hyponatraemia results from proximal tubular reabsorption of sodium and water with non-osmotic release of vasopressin. The first sign of hepatorenal syndrome is usually oliguria. The major differential diagnoses include prerenal azotaemia and vasomotor nephropathy (acute tubular necrosis). The patient with hepatorenal syndrome appears well hydrated and volume depletion can usually be excluded. The fractional excretion of sodium (FE&subN;&suba;) is less than 1 per cent and the urinary sodium less than 10 to 15 mmol/1, in contrast to vasomotor nephropathy, which characteristically has a high urinary sodium content—over 30 mmol/1. If prerenal azotaemia is suspected a cautious fluid challenge consisting of about 250 ml of crystalloid or colloid infused over 30 min can be tried. If doubt remains regarding the volume status of the patient, a flow directed pulmonary artery catheter should be inserted for accurate assessment of left heart filling pressures. The urine sediment should be examined carefully. The presence of cellular casts suggests vasomotor nephropathy rather than hepatorenal syndrome. Obstructive uropathy should be excluded by renal ultrasound or if necessary, retrograde pyelography.

When treating any patient with advanced liver disease, it is essential to avoid factors that precipitate the hepatorenal syndrome. Adequate nutrition must be maintained and electrolyte abnormalities corrected. Diuretics should be used judiciously and ascites drained only for specific indications. Any intercurrent infection must be treated aggressively. The use of certain drugs, such as the non-steroidal anti-inflammatory agents, angiotensin-converting enzyme inhibitors, and tetracyclines should be avoided and aminoglycosides should not be used unless this is unavoidable.

There is currently no specific treatment for the hepatorenal syndrome: therapy is directed at supporting the underlying liver disease. Haemodialysis and haemofiltration may control the metabolic disturbances of renal failure but the outcome is determined by the degree of liver impairment. A summary of these supportive measures is shown in Table 2 80.

Pharmacological agents that have been used in an attempt to reverse the hepatorenal syndrome include dopamine, isoproterenol (isoprenaline), phenoxybenzamine, phentolamine, aminophylline, mannitol, metaraminol, epinephrine (adrenaline), papaverine, and prostaglandin A1. All have been without effect in double-blind studies. Recovery of renal function has occurred following peritoneojugular (LaVeen) and portacaval shunting procedures. Orthotopic liver transplantation appears to offer the best hope for reversal of the hepatorenal syndrome but is only available for a relatively small group of suitable patients.

Abdominal ascites is a common feature of the patient with the hepatorenal syndrome. The common indications for reduction of ascites include abdominal pain, intravascular coagulation and renal vein compression, gastro-oesophageal reflux (with erosion of varices), and restriction of ventilation by diaphragm splinting. Simple measures such as bed rest and salt restriction are essential preliminary measures. Spironolactone or amiloride, combined if necessary with a loop diuretic, can then be added. In a proportion of patients direct drainage of ascitic fluid is required. The aim is to drain sufficient fluid to alleviate symptoms without inducing the hepatorenal syndrome. Infusion of colloid should accompany the paracentesis to ensure that the patient does not become volume depleted. Paracentesis is occasionally followed by a brisk diuresis, particularly if the renal veins have been compressed by the ascitic fluid.

Mild acute pancreatitis has a mortality of less than 3 per cent and rarely requires critical care management. Ten per cent of patients with pancreatitis have severe disease, however, accompanied by multiple organ system failure. Although early reports of severe acute pancreatitis were associated with a mortality of up to 75 per cent more recent mortality figures have fallen towards 20 per cent. Most cases of pancreatitis are the result of either alcohol abuse or cholelithiasis. Other causes of pancreatitis are listed in Table 3 81.

Acute pancreatitis should be considered in any patient presenting with abdominal pain, nausea, and vomiting. Other common clinical signs and symptoms of acute pancreatitis are shown in Table 4 82. Abdominal pain is invariably present and radiates to the back in 50 per cent of patients. Acute haemorrhagic pancreatitis often presents dramatically with shock, confusion, coma, oliguria, and abdominal ecchymoses.

Laboratory confirmation usually rests on the detection of elevated levels of serum or urinary amylase. Elevated serum amylase also may be found in patients with intestinal obstruction, bowel perforation or infarction, pregnancy, renal failure, major burns, and carcinomas of the lung, oesophagus, or ovary. Isoenzyme analysis may help differentiate pancreatic and salivary sources of amylase.

The treatment of severe acute pancreatitis can follow either of two philosophies. The first involves the surgical removal of necrotic material to reduce the risk of organ system failure and secondary infection. The second adopts a conservative approach delaying surgery until indicated for complications such as haemorrhage or infection.

Regardless of the management philosophy, the critical care treatment during the acute, toxaemic phase is directed at the management of primary pancreatic failure (diabetes mellitus), hypovolaemia secondary to fluid sequestration, and multiple organ system failure. Analgesia can be achieved using agents such as pethidine or a synthetic opiate (alfentanil). Morphine probably should be avoided in view of a propensity to cause spasm of the sphincter of Oddi.

Late complications result from local, intra-abdominal, and systemic infection and often progress to the sepsis syndrome. This late phase has a significant effect on the final mortality from acute pancreatitis and requires all the resources of the critical care unit.

Hyperglycaemia and ketoacidosis require volume replacement, continuous insulin infusion according to blood sugar levels (2–8 units/h is generally adequate), provision of intravenous dextrose, and correction of electrolyte imbalance. Metabolic acidosis can also result from lactic acidosis and, occasionally, from renal failure.

Hypocalcaemia occurs in about 25 per cent of patients, usually within the first week of the illness. Hypocalcaemia is associated with hypoalbuminaemia, calcification of areas of intra-abdominal fat necrosis, and parathyroid dysfunction.

Treatment is supportive, there being no specific, effective therapeutic agent available. Drugs such as somatostatin, glucagon, cimetidine, aprotinin (trasylol), and anticholinergics do not appear to be effective. Peritoneal lavage is favoured by some, as is open drainage of the pancreatic bed following pancreatectomy. Much more extensive and controlled evaluation of these forms of treatment is required.

Any of the major organ systems can be involved in patients with acute pancreatitis. Organ system failure in pancreatitis is one of the most common indications for critical care unit admission. Since organ system failure is responsible for most of the deaths associated with pancreatitis, prevention, or at least early recognition, is paramount.

The electrocardiogram may show prolongation of the ST interval and non-specific T-wave changes. Tachyarrhythmias can develop and are probably related to the metabolic abnormalities of pancreatitis or coexistent alcoholic cardiomyopathy. Hypotension may result from bradykinin release and abdominal fluid sequestration. The intravascular fluid deficit can be large, requiring several litres for replacement, and central venous pressure monitoring is generally required. The nature of the replacement fluid is probably less critical than the volume. Fluid resuscitation should continue until a central venous pressure of about 10 mmHg can be achieved and satisfactory urine output of 0.5 to 1.0 ml/kg.min is maintained.

More than half of all patients with pancreatitis will have chest radiographic changes such as patchy infiltrates, collapse, or pleural effusion. Pleural effusions of an exudative type occur in up to 15 per cent of patients, the left hemithorax being most commonly involved. Arterial hypoxaemia is evident in up to 75 per cent of patients: this usually responds to supplemental oxygen but about 20 per cent of patients require endotracheal intubation and positive pressure ventilation.

Leucocytosis, fever, and complement activation are features of acute pancreatitis. As with all intensive care patients, nosocomial infection is increasingly likely after the second week of admission. However, use of antibiotics should be reserved for patients with clear signs of infection of sepsis. Prophylactic antibiotics are not recommended.

Gastric erosions and ileus are common accompaniments of acute pancreatitis. Prophylaxis against stress associated gastric erosions and total parenteral nutrition should be provided for the mechanically ventilated patient. Ulcer prophylaxis can be provided by cytoprotective agents (sulcralfate), antacids, or H&sub2; blockers. The last increase gastric pH, and may increase the risk of nosocomial pneumonia.

Anaemia may result from pancreatic or gastric bleeding. Patients with alcoholic cirrhosis and oesophageal varices are at further risk of gastrointestinal haemorrhage. Prolongation of prothrombin time may occur due to coexistent liver failure or disseminated intravascular coagulation: replacement of clotting factors with fresh frozen plasma is indicated, particularly if there is active bleeding. Platelet transfusion also may be required if there is bleeding in the presence of a platelet count of less than 50000/mm³.

Prerenal azotaemia and vasomotor nephropathy will occur unless rigorous fluid resuscitation is undertaken. Any fall in hourly urine volumes to below 0.5 ml/min.kg should prompt an immediate evaluation of the volume status of the patient using all measures available. In established renal failure haemofiltration provides a convenient means of controlling the fluid balance, electrolyte balance, and azotaemia. Only rarely is haemodialysis is required.

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