Composition

Most commercially available enteral feeds have an energy content of 1 to 2 kcal/ml; a value of 1.0 to 1.2 kcal/ml is typical (Table 34-1). Thus, a 70-kg patient receiving 25 kcal/kg/day has an obligatory fluid load of 1 to 2 l/day. Nitrogen is administered as protein (e.g., a soy isolate), carbohydrate as polysaccharides (e.g., corn syrup or hydrolyzed corn starch), and fat as triglycerides (e.g., canola oil). Micronutrients are added in appropriate quantities. Fiber and electrolytes are present in variable amounts.

A wide variety of different enteral feeds are available for use in specific circumstances; only some of them are clinically useful. Elemental feeds, in which the nitrogen content is provided as amino acids, are useful in patients with short bowel syndrome, pancreatic insufficiency, and radiation enteritis, but they offer no advantage in the critically ill. Renal formulations that are calorie dense (typically 2 kcal/ml) and low in volume, sodium, and potassium are available. They are useful in patients with oliguric renal failure but should not be used in lieu of renal replacement therapy when it is indicated (see Chapter 33). Formulations for patients with diabetes, in which the carbohydrate content is reduced and the protein and fat content is increased, are available. However, the high protein content may be inappropriate for patients with renal dysfunction, and hyperglycemia is best managed by intravenous insulin rather than by carbohydrate restriction. Thus, diabetic formulations are infrequently used in the ICU. The use of so-called immune-enhancing feeds is controversial. Guidelines do not support the use of arginine-enriched feeds, but they offer limited support for the use of feeds supplemented by glutamine (for patients with burns and trauma) and by fish oils, borage oils, and antioxidants (for patients with acute respiratory distress syndrome).¹⁶ Formulations that are high in fat (50% of calories) and low in carbohydrate and sodium are available for use in patients with acute respiratory distress syndrome; they may have a role in selected patients who have hypercarbic respiratory failure.

Route of Administration and Feeding Protocols

Nasogastric Feeding.

Consensus guidelines recommend starting enteral nutrition within 24 to 48 hours of ICU admission.¹⁶ Therefore, in all patients who are not expected to be extubated within 24 to 48 hours of surgery, a 12F or 14F nasogastric tube should be inserted on the first postoperative day. If the hemodynamic state permits, patients should be nursed at a 45-degree head-up position to help prevent aspiration of gastric contents and reduce the incidence of ventilator-associated pneumonia.²³ Patients with intraaortic balloon pump in situ may be safely nursed at a 20-degree head-up position. Nasogastric feeding should be commenced at a low rate (e.g., 20 ml/hr). In critically ill patients who are receiving high doses of inotropic drugs, it may be prudent to maintain this low rate for the first 24 to 48 hours. Otherwise, the rate should be increased incrementally to the goal value according to protocol, an example of which is shown in Figure 34-1. The target rate should be determined on an individual basis. Aspirates in excess of 200 ml are indicative of gastric stasis. Metoclopramide (10 mg every 6 hours intravenously) may be used to promote gastric motility, but it is only weakly effective. Erythromycin is a more effective prokinetic than metoclopramide, but because it is potentially proarrhythmic and may promote antimicrobial resistance, its use for this purpose is not recommended.¹⁶

Figure 34.1 Algorithm for commencing nasogastric feeding.

Adverse Effects

Apart from hyperglycemia—which should be treated with intravenous insulin—the metabolic consequences of overfeeding that were described earlier are uncommon with enteral nutrition. Diarrhea and constipation are common, each occurring in about 15% of enterally fed patients.²⁴ Other commonly reported adverse effects include gastric stasis (39%), abdominal distention (13%), vomiting (12%), and regurgitation (5%).²⁴ There is no difference in the incidence of aspiration between gastric and postpyloric feeding.²⁵ Occasionally, a large volume (>1 to 2 l/day) of gastric fluid is aspirated from the stomach despite successful postpyloric feeding. If this fluid is discarded, hypovolemia and hypochloremic metabolic alkalosis can develop. The treatment is intravenous 0.9% saline. Intolerance of nasogastric nutrition is very common and is not necessarily a cause for concern; intolerance of postpyloric feeding is less common and may indicate intraabdominal pathology (see subsequent material).

Sinusitis can occur when nasogastric or nasojejunal feeding tubes are in situ for long periods. Polyurethane or silicone feeding tubes should be used when enteral feeding is anticipated to be used for longer than 2 weeks because polyvinylchloride tubes progressively degrade during contact with gastric contents.²⁶

Weaning

As patients recover from critical illness and are weaned from mechanical ventilation, they start to eat, and tube feeding is reduced and then discontinued. During this process the patient’s caloric and protein intake should be closely monitored. For patients who are fed postpylorically and have low nasogastric aspirates, nasogastric feeding may be commenced. If this is tolerated, the nasojejunal tube may be withdrawn and full nasogastric feeding instituted. Once the patient is able to tolerate oral intake, nasogastric feeding may be limited to overnight, with feeding stopped 1 to 2 hours before breakfast. High-calorie liquid supplements, similar in energy content and composition to 1.5 kcal/ml enteral feeds, may be used to support oral intake during the day.

Composition

Parenteral nutrition is provided in elemental form: nitrogen as L-amino acids, carbohydrate as glucose, and fat as fatty acids. The appropriate proportion of nitrogen, carbohydrate, and fat is the subject of debate, but a ratio similar to that used for enteral nutrition is common. The advantage of a relatively high proportion of fat is the avoidance of hyperglycemia secondary to high glucose administration; the disadvantage is a potentially increased incidence of nosocomial infection.²⁷ If it is anticipated that parenteral nutrition will be required for fewer than 10 days in a patient who is not malnourished, withholding lipids should be considered.¹⁶ Vitamins and trace elements are added in appropriate amounts.

Variable amounts of sodium, potassium, calcium, magnesium, buffer, and water are added to suit patients’ needs. Many patients require water restriction, and a minimum volume of 1 liter per 24 hours is usually possible. Daily sodium and potassium requirements are discussed in Chapter 32. Many patients receiving parenteral nutrition have expanded extracellular spaces and require very little, if any, sodium. Potassium requirements may be high because of insulin treatment given for hyperglycemia or low due to renal failure. Anions are provided as a mixture of chloride and acetate, with a small amount of phosphate. Relatively more chloride may be used in patients with alkalosis, and relatively more acetate may be used in patients with acidosis.

Route of Administration

Parenteral nutrition is hypertonic and must be administered via a central venous catheter. To minimize the risk of infection, it should be a dedicated single-lumen catheter inserted either peripherally or into the subclavian vein (see Chapter 40). Three-way taps in the infusion set should be avoided, and the delivery tubing and any remaining nutrition should be changed each day using aseptic precautions.

Adverse Effects and Biochemical Testing

Problems of overfeeding and infection are more common with parenteral than enteral nutrition. Abnormalities of acid-base status and glucose and electrolyte concentrations are common, particularly during the initiation and cessation of treatment. During the first few days of treatment, blood sugar should be measured at least every 6 hours and potassium twice daily. Plasma concentrations of magnesium, calcium, phosphate, urea and creatinine, albumin, amylase, liver function, and triglycerides, along with a complete blood count and coagulation profile, should be measured every 1 to 3 days initially. Zinc should be measured weekly. A triglyceride concentration above 4.5 mmol/l (>400 mg/dl) is an indication to reduce or stop the fat component of parenteral nutrition.

Hyperglycemia should be treated with intravenous insulin (see Chapter 36). Hypoglycemia can occur with abrupt cessation of treatment, so when it is no longer required, patients should be weaned from parenteral nutrition slowly over several hours. If for some reason the daily supply is interrupted, patients should be commenced on a dextrose infusion at a rate similar to the concentration in the parenteral nutrition.

Abnormalities in liver function tests are common, and both hepatocellular and cholestatic patterns are seen, but jaundice is uncommon. The problem may resolve with a reduction in calories.

Chronically malnourished patients who receive aggressive nutritional support, particularly via the intravenous route, are at risk of the refeeding syndrome.^28,29 This condition is characterized by disturbances in the balance of body sodium and water (hypovolemia with predominantly protein feeding and hypervolemia with predominantly carbohydrate feeding), hypophosphatemia, hypokalemia, hypomagnesemia, and thiamine deficiency (manifested as Wernicke encephalopathy). Thiamine (100 mg intravenously daily for 3 days) should be given before commencing feeds if malnutrition is suspected. Profound hypophosphatemia can cause myopathy and rhabdomyolysis. Refeeding syndrome is very uncommon in postoperative cardiac surgery patients. Complications that involve vascular access devices are listed in Chapter 40.

Ileus

Ileus is a reversible reduction in gastrointestinal motility resulting in delayed passage of enteric contents. Ileus may involve the stomach (gastric stasis), small bowel, or colon. Gastric stasis is common and was discussed earlier. The causes of small bowel ileus are listed in Table 34-3. Patients have abdominal distension and are intolerant of postpyloric feeding. Colicky abdominal pain is uncommon. Bowel sounds may be absent. The radiographic findings are listed in Table 34-2. Treatment is conservative, and the condition typically resolves within a few days.

Table 34-3 Causes of Postoperative Ileus

Mechanical Obstruction

Mechanical obstruction is uncommon following cardiac surgery but, because it may require surgical intervention, the diagnosis must always be considered. Causes of mechanical obstruction include volvulus (a twisting of the bowel upon itself, typically involving the ileum, cecum, or sigmoid colon), internal hernias, and fecal impaction. Patients may report colicky, cramping abdominal pain. Bowel sounds are usually present. A rectal examination should be performed to exclude fecal impaction. The diagnosis may be confirmed by abdominal radiography (see Fig. 34-2) or CT.

Mechanical bowel obstruction is a surgical emergency; untreated, it can lead to ischemia or perforation of the bowel and fecal peritonitis. Cecal dilatation greater than 12 cm on radiographic imaging represents a high risk for perforation and is an indication for laparotomy. Volvulus of the sigmoid colon may be decompressed via colonoscopy. Volvulus involving the cecum or ileum typically requires a laparotomy.

Pseudoobstruction

Pseudoobstruction is a syndrome of colonic atony, which results in severe dilation and functional obstruction. The condition typically develops in unwell, hospitalized patients. It is often self-limiting, but occasionally it results in progressive colonic dilation, with the attendant risk for ischemia and perforation.³¹ Pseudoobstruction is commonly confused with mechanical obstruction because both conditions result in colicky abdominal pain and tympanic abdominal distension. Abdominal radiographs may help to distinguish between the two conditions (see Table 34-2).

Treatment is initially conservative. If distension has not resolved after 24 to 48 hours of conservative management, treatment with intravenous neostigmine (2.5 mg)³² or colonoscopic decompression should be considered. Neostigmine is a cholinomimetic agent that increases colonic motility. A single dose may lead to copious diarrhea and sustained abdominal decompression. However, in the presence of mechanical obstruction, neostigmine can precipitate intestinal perforation. Thus, it is essential that mechanical obstruction be excluded before administering neostigmine. In general, neostigmine should not be given unless bowel gas can be seen in the rectum and sigmoid colon; the absence of gas in the distal colon may indicate a mechanical obstruction. Patients who fail to respond to these measures or who have cecal dilatation greater than 12 cm on an abdominal radiograph should be referred to a gastrointestinal surgeon.

Pathogenesis

Mesenteric ischemia is not a single entity; it represents a continuum that ranges from self-limited, subclinical ischemia to fully developed infarction involving most of the gut. A number of mechanisms are recognized, including splanchnic hypoperfusion, arterial embolism, arterial or venous thrombosis, and gross bowel distension due to mechanical or pseudoobstruction. Many patients who develop mesenteric ischemia have experienced antecedent hemodynamic instability or shock. With shock, there is intense splanchnic arteriolar vasoconstriction, which can cause mesenteric hypoperfusion and ischemia. This may be exacerbated by exogenously administered vasopressors, particularly in the setting of hypovolemia. Mesenteric arterial atherosclerosis and high systemic (and thus portal) venous pressure, such as occurs with right ventricular failure and pericardial tamponade, also impairs splanchnic perfusion. Systemic arterial embolism may occur as the result of an intracardiac thrombus, a ruptured atherosclerotic plaque, or calcified debris from the aorta or aortic valve. Aortic dissection may involve the mesenteric arterial supply.

Ischemia begins within the mucosa and extends outward. Thus, early ischemia or infarction may be missed at laparotomy. The distribution of ischemia is varied but most commonly involves the territories of the superior (distal ileum to transverse colon) or inferior (transverse colon to sigmoid colon) mesenteric arteries. Infarction involving the distribution of the celiac axis (stomach and proximal small bowel) is uncommon. When ischemia involves the territory of the superior mesenteric artery (or celiac axis), full-thickness infarction commonly develops. Full-thickness infarction results in the release of multiple inflammatory mediators from the gut and the translocation of enteric bacteria into the circulation (see Chapter 2). This typically leads to vasodilatory shock and multiple organ dysfunction syndrome. Mortality rates are very high. By contrast, insufficiency involving the territory of the inferior mesenteric artery may result in ischemia or infarction that is limited to the mucosa or submucosa, in which case shock and multiple organ dysfunction syndrome are less likely to develop, and mortality rates are lower.

Risk Factors

The risk factors for mesenteric ischemia and infarction are outlined in Table 34-4. Mesenteric ischemia, particularly when it develops as a consequence of hypoperfusion, typically occurs in critically unwell patients. Such patients are usually receiving mechanical ventilation, high-dose inotropic support, renal replacement therapy and, occasionally, mechanical cardiac support.³³ Rarely, mesenteric ischemia develops due to systemic arterial embolism in a patient who is otherwise making an uneventful recovery.

Table 34-4 Risk Factors for Mesenteric Infarction Following Cardiac Surgery

From Venkateswaran RV, Charman SC, Goddard M, et al: Lethal mesenteric ischaemia after cardiopulmonary bypass: a common complication? Eur J Cardiothorac Surg 22:534-538, 2002; Garofalo M, Borioni R, Nardi P, et al: Early diagnosis of acute mesenteric ischemia after cardiopulmonary bypass. J Cardiovasc Surg 43:455-459, 2002; Gennaro M, James J, Sheikh A, et al: Acute mesenteric ischemia after cardiopulmonary bypass. Am J Surg 166:231-236, 1993; and Chaudhuri N, James J, Sheikh A, et al: Intestinal ischaemia following cardiac surgery: a multivariate risk model. Eur J Cardiothorac Surg 29:971-977, 2006.

Clinical Assessment

Mesenteric ischemia is notoriously difficult to diagnose clinically. The early signs are nonspecific: abdominal pain, abdominal distension, and intolerance of enteral nutrition. As infarction develops, patients typically develop shock, anuric renal failure, lactic acidosis, and an acute surgical abdomen, with severe pain and signs of peritonism (rebound tenderness, guarding). If the cause is hypoperfusion, abdominal pain may develop gradually, whereas if the cause is embolic, pain may develop abruptly.

Often, the first sign of evolving mesenteric infarction in a sedated patient is hemodynamic deterioration in association with renal dysfunction and nonspecific abdominal signs. Presentation usually occurs between 3 days and 2 weeks after surgery, rarely earlier.³³

Ischemic colitis involving the territory of the inferior mesenteric artery is a distinct clinical entity. Patients typically present with left-sided abdominal pain and bloody diarrhea. Shock is rare.

Investigations

Routine blood tests (blood gases, electrolytes, glucose, urea and creatinine, liver function tests, amylase, complete blood count, coagulation profile) and supine and decubitus plain abdominal radiographs should be obtained in all patients with suspected mesenteric infarction. In patients who have signs of sepsis or shock, blood should be sent for microbiologic culture.

Abnormalities suggestive of mesenteric ischemia or infarction include leukocytosis, abnormal liver function tests, elevated amylase, and hyperphosphatemia. However, none of these findings are sensitive or specific for mesenteric ischemia, and all may be absent early in the clinical course. Lactic acidosis is a common finding with fully developed infarction, but it may be absent early in the clinical course. Other causes of lactic acidosis (see Chapter 31) and hyperlactatemia must be considered.

On the supine radiograph, the presence of gas within the bowel wall or the portal venous system is highly suggestive of mesenteric infarction (Fig. 34-4). However, these signs are easily missed or may be absent, particularly early in the clinical course. With ischemia, dilation of the bowel lumen and edema of the bowel wall are common findings but are nonspecific. Occasionally, free intraperitoneal air, suggestive of bowel perforation, is identified on a decubitus abdominal film or erect chest radiograph. (It is important to note that a small amount of subdiaphragmatic free air is a normal finding in postoperative cardiac surgery patients; it results from a breach in the peritoneum at the lower end of the sternal wound or from subxiphisternal chest drains.)

Figure 34.4 Supine plain abdominal radiograph showing gas in the biliary tree (arrow) secondary to mesenteric infarction. A nasojejunal feeding tube can be seen.

Confirmatory evidence of mesenteric ischemia or infarction may be obtained by means of an abdominal CT scan, ideally using oral and intravenous contrast and scanning in the arterial and portal venous phases (i.e., a mesenteric CT angiogram). The use of intravenous contrast must be carefully considered because concomitant renal failure is common. If CT scanning is performed without intravenous contrast, assessment of vascular patency is not possible. However, the identification of bowel wall edema or gas (Fig. 34-5), bowel dilatation, and free intraperitoneal air or fluid is still possible. CT scanning is useful in patients who are hemodynamically stable and in whom there is genuine diagnostic uncertainty. However, in patients with advanced abdominal signs and shock, it is more appropriate to proceed directly to laparotomy.

Figure 34.5 CT scan showing signs of mesenteric ischemia. The cecum is distended and air can be seen within its wall (arrows). The wall of one loop of small bowel also appears thickened (large arrow).

Differential Diagnosis

The differential diagnosis depends on the mode of presentation. Nonspecific abdominal signs are common in postoperative cardiac surgery patients and are only rarely indicative of mesenteric ischemia or infarction. Severe abdominal pain may by due to obstruction, perforated viscus, peptic ulcer disease or, occasionally, intrathoracic pathology such as aortic dissection, myocardial infarction, or pneumothorax. With rapidly escalating inotropic support or fulminant shock, the differential diagnosis includes cardiac dysfunction and extraabdominal septic shock. Profound lactic acidemia (pH <7.1, lactate >10 mmol/l) in the absence of low cardiac output is strongly suggestive of mesenteric or hepatic ischemia or infarction. Septic shock, ischemic hepatitis, and primary cardiac dysfunction may all coexist with mesenteric infarction.

Treatment

Untreated, full-thickness mesenteric infarction is uniformly fatal. If there is a high index of suspicion, urgent referral to a gastrointestinal surgeon for laparoscopy or laparotomy is indicated. In stable patients, laparoscopy may be the intervention of choice; the bowel can be inspected and a decision to proceed to laparotomy made if appropriate. In patients with shock, insufflation of the peritoneal space to facilitate laparoscopy may cause hemodynamic collapse; such patients should undergo laparotomy. If infarcted bowel is identified, it should be resected. If segments of bowel appear hypoperfused but potentially viable, a second-look laparotomy 24 to 48 hours later may be appropriate. Massive infarction involving all or most of the intestines is uniformly fatal. In this situation, it is not appropriate to attempt resection, and the patient should be returned to the ICU and be provided with comfort cares (see Chapter 39). Patients with suspected ischemic colitis should undergo colonoscopy. If the diagnosis is confirmed, and assuming the patient remains stable, conservative management is appropriate. A repeat colonoscopy 24 to 72 hours later may be indicated to assess progress.

Fluid and inotropic therapy guided by invasive hemodynamic monitoring should be used to optimize global and splanchnic perfusion. In cases of vasodilatory shock, norepinephrine, either alone or in combination with dobutamine, is the inotrope of choice.^35,36 Splanchnic perfusion appears to be worse with epinephrine than with norepinephrine.³⁷ Vasopressin may worsen splanchnic perfusion³⁸ and is best avoided. Low cardiac output should be treated by an inodilator such as dobutamine or milrinone. Severe lactic acidemia may be treated by hemofiltration using bicarbonate buffered substitution fluid (see Chapter 33).

Diagnosis and Treatment

Patients with minor upper gastrointestinal bleeding should continue to be fed enterally and commenced on a proton pump inhibitor (e.g., omeprazole 40 mg daily). Bleeding that is associated with hemodynamic instability or the need for transfusion of four or more units of blood should be investigated by means of urgent upper gastrointestinal endoscopy. Not only is endoscopy diagnostic, it is also prognostic and may be therapeutic. The finding of an actively bleeding ulcer, a nonbleeding vessel in an ulcer, or clot in the base of an ulcer identifies patients at high risk for further bleeding. These patients should be given high-dose proton pump inhibitor therapy (e.g., 80 mg omeprazole followed by an infusion of 8 mg/hr for 24 hr).⁴⁰ At the time of endoscopy, epinephrine may be injected into and around a bleeding ulcer, electrocoagulation can be used to cauterize bleeding sites, or hemoclips may be applied to a bleeding vessel. If upper gastrointestinal endoscopy is normal and there is persistent blood loss, colonoscopy or CT mesenteric angiography should be performed. Coagulopathy should be corrected as described in Chapter 30. In patients who have undergone anticoagulation by warfarin or heparin, the risks of thrombosis associated with the reversal of anticoagulation must be weighed against the risk of further bleeding.

The indications for laparotomy include persistent or recurrent bleeding despite endoscopic attempts at hemostasis, massive transfusion (>6 units of red cells), and perforation. As noted earlier, viscus perforation may be difficult to diagnose in cardiac surgery patients because a small amount of free intraperitoneal air can be a normal finding. As an alternative to laparotomy, angiography and embolization may be considered in patients with active bleeding (>0.5 ml/min) and severe systemic disease who are poor candidates for surgery.

Following gastrointestinal hemorrhage, there is systemic absorption of hemoglobin. Metabolism of the protein results in an increased concentration of blood urea nitrogen without an increase in the concentration of plasma creatinine. Metabolism of heme results in an increased plasma concentration of unconjugated (indirect) bilirubin.

Stress Ulcer Prophylaxis in Cardiac Surgery Patients

Acid prophylaxis in high-risk ICU patients reduces the risk for stress ulceration⁴¹ but leads to gastric colonization by enteric gram-negative microorganisms and increases the risk of developing ventilator-associated pneumonia.²³ There are no data supporting routine acid prophylaxis in cardiac surgery patients, but therapy is probably justified in patients at high risk for stress ulceration, such as those who are or have been shocked, have been ventilated for longer than 48 hours, or have been treated with anticoagulants. If patients have been receiving ulcer prophylaxis preoperatively, it should be recommenced immediately after surgery. Sucralfate is associated with a lower incidence of ventilator-associated pneumonia than is ranitidine,²³ but sucralfate is less effective than ranitidine in preventing stress ulceration.⁴² Proton pump inhibitors (e.g., omeprazole or pantoprazole) appear to be more effective than ranitidine for prophylaxis of stress ulcers,^43,44 so they are the preferred agents.

Liver Function Tests

Between 15% and 20% of patients develop transient increases in plasma liver enzyme levels following cardiac surgery.¹ Abnormal results of liver function tests may be seen because of preexisting liver dysfunction (e.g., viral hepatitis, cirrhosis, biliary tract disease) or may arise de novo during the postoperative period.

Two basic patterns of liver dysfunction are recognized: hepatocellular, characterized by elevated hepatic transaminases (aspartate aminotransferase and alanine aminotransferase); and cholestatic, characterized by elevated alkaline phosphatase and conjugated (direct) bilirubin. Jaundice is usually apparent when the bilirubin concentration exceeds 50 μmol/l (3.0 mg/dl).⁴⁵ The common causes of abnormal results of liver function tests in ICU patients are listed in Table 34-5.

Table 34-5 Common Causes of Abnormal Liver Function Tests

Increased levels of unconjugated (indirect) bilirubin imply increased red blood cell destruction. In cardiac surgery patients, this is usually caused by reabsorption of shed blood (e.g., by a retroperitoneal hematoma or gastrointestinal bleed) or by intravascular hemolysis secondary to prosthetic valve regurgitation. Intravascular hemolysis is confirmed by the finding of elevated plasma-free hemoglobin, reduced plasma haptoglobin, and increased reticulocyte count.

Cholestatic jaundice often develops in critically unwell patients with multiple organ dysfunction syndrome. The mechanism is unclear and no specific treatment is required. However, it is important to rule out other causes of jaundice, such as intravascular hemolysis, cholecystitis, and drugs. Conjugated and unconjugated bilirubin fractions should be measured, along with plasma haptoglobin concentration and reticulocyte count. A right upper quadrant abdominal ultrasound should be obtained to look for evidence of biliary tract obstruction or cholecystitis.

Severe, chronic hepatic disease leads to reduced protein synthesis by the liver. This is manifested as hypoalbuminemia and an elevated prothrombin time. A low plasma albumin concentration also occurs with malnutrition, congestive heart failure, systemic inflammation, and gastrointestinal or renal protein loss. In cardiac surgery patients, preoperative hypoalbuminemia is a powerful predictor of postoperative adverse outcome,⁴⁶ presumably because it represents poor nutritional state or severe chronic disease.

Drugs and the Liver

Various drugs are associated with the development of abnormal results of liver function tests (Table 34-6). Some drugs (e.g., flucloxacillin) typically produce a cholestatic pattern; others (e.g., fluconazole), a hepatocellular picture. With many drugs, both patterns can occur. Most drug-induced hepatic injury is idiosyncratic; that is, only some patients develop hepatotoxicity, and the effect is not directly related to the dose of the drug. Other drugs, notably acetaminophen, cause dose-dependent hepatotoxicity.

Table 34-6 Hepatotoxicity Associated With Drugs Commonly Used in the ICU

Note: All agents except acetaminophen cause idiosyncratic hepatotoxicity. Acetaminophen hepatotoxicity results primarily from the cumulative effects of the drug. Idiosyncratic and cumulative hepatotoxicity occurs with amiodarone and cyclosporine.

Ideally, if a drug is implicated as a potential cause of liver dysfunction, it should be stopped. This is particularly the case for acetaminophen, which has the potential to cause fatal hepatotoxicity. For other drugs, such as antimicrobials, it may be reasonable to continue treatment and closely monitor liver function.

With liver dysfunction, dosage reductions must be made in a number of hepatically metabolized drugs (Table 34-7).⁴⁷ Failure to do so may exacerbate hepatic dysfunction or result in an increased pharmacologic effect due to reduced hepatic clearance. Hepatically mediated drug interactions are listed in Table 4-3.

Table 34-7 Drugs That Should Be Given at Reduced Dosages or Avoided in Patients With Liver Dysfunction

Modified from Chernow B: The Pharmacologic Approach to the Critically Ill Patient, ed 3. Baltimore, Williams and Wilkins, 1994, p. 98.

Hepatic Congestion

Increased systemic venous pressure from any cause leads to hepatic congestion. The liver becomes enlarged, pulsatile, and tender. Transaminases, alkaline phosphatase, and conjugated (direct) bilirubin become moderately elevated. Occasionally, jaundice and an elevated prothrombin time occur. There may be signs of tricuspid regurgitation or right ventricular failure. An ultrasound examination of the liver and biliary tract should be obtained to rule out hepatic vein thrombosis and biliary tract disease. An echocardiogram may demonstrate right ventricular dysfunction, tricuspid regurgitation, or pulmonary hypertension. Treatment is directed to the underlying cause.

Hepatic Ischemia and Acute Liver Failure

Hepatic ischemia is a common accompaniment of severe shock, particularly if it is associated with high systemic venous pressure such as that which occurs with right ventricular failure or following cardiac arrest. Acute hepatic ischemia is characterized by a ten- to fortyfold increase in hepatic transaminases. Bilirubin, alkaline phosphatase, and the prothrombin time are typically normal or only mildly increased. Resolution of biochemical abnormalities occurs with correction of the precipitating cause, although elevated transaminases take 7 days to normalize.

Occasionally, profound hepatic ischemia results in acute liver failure, the features of which include reduced level of consciousness due to cerebral edema, vasodilatory shock, oliguric renal failure, coagulopathy, lactic acidosis, and hypoglycemia. The findings of markedly elevated transaminases in association with lactic acidosis and hypoglycemia are strongly suggestive of acute liver failure. Treatment of hypoglycemia, coagulopathy, acidemia, coma, and raised intracranial pressure may be required. Unremitting lactic acidosis may be treated with hemofiltration using bicarbonate-buffered replacement solution (see Chapter 33). Mortality rates are very high.

Cholecystitis

Acute cholecystitis is a rare but well-recognized occurrence following cardiac surgery.^1,48 Patients typically present with right upper quadrant abdominal pain, fever, and cholestatic jaundice. The diagnosis is usually confirmed by ultrasonography of the liver and biliary tract. Gallstones are absent in about one third of cases.¹ The pathologic mechanism of acalculous cholecystitis is edema and obstruction of the cystic duct. Treatment of cholecystitis includes nil by mouth and broad-spectrum antimicrobials. Perforation of the gallbladder may occur, so urgent referral to a hepatobiliary surgeon is indicated.