Failure to open bowels Common ICU causes \200 \200 \200 Prolonged ileus/decreased gut motility (e.g. opiates, post-surgery). Lack of enteral nutrit ion. Bowel obstruction \200\224this is a relatively uncommon secondary event and is mainly seen post-operatively, either after a curative procedure or with development of adhesions. Management \200 Clinically exclude obstruction and con \201 rm presence of stool per rectum. Ensure adequa te hydration. Anti-constipation therapy may be given, usually starting with laxatives (e.g. lactulose or, for more urgent response, magnesium sulfate), then proceeding to glycerin su ppositories, and \201 nally, enemata if gentler measures prove unsuccessful. Consider red ucing/stopping dose of opiate if possible. For colonic pseudo-obstruction, consider 2mg IV neostigmine. \200 \200 FAILURE TO OPEN BOWELS 411 Key paper Robert J. Ponec RJ, Saunders MD, et al. (1999) Neostigmine for the treatment of a cute colonic pseudo-obstruction. N Engl J Med 341: 137 \200\22341. See also: Anti-constipation agents, p298; Intra-abdominal bowel perforation and obstruction , p418; Abdominal sepsis, p422; Pancreatitis, p424. 412 CHAPTER 25 Gastrointestinal disorders Upper gastrointestinal hemorrhage Causes \200 \200 \200 \200 \200 Peptic ulceration. Oesophagitis/gastritis/duodenitis. Varices. Mallory \200\223Weiss lower oesophageal tear. Neoplasms. Pathophysiology Peptic ulceration is related to protective barrier loss leading to acid or biliary damage of the underlying mucosa and submucosa. Barrier loss occurs secondary to cri tical illness, alcohol, and drugs, e.g. non-steroidals, poisons, including corrosives. Dire ct damage, especially at the lower esophagus, may occur from feeding tubes. Mucosal damage ( \200\230stress ulcers \200\231) may also occur as a consequence of tissue hypoperfusion. Gastric hypersecretion is uncommon in critically ill patients; indeed, gastric acid content and secretion are often reduced. Prophylaxis \200 \200 Small-bore feeding tubes. Nasogastric enteral nutrition (even nasojejunal and parenteral fe eding have also been shown to reduce the incidence of stress ulcer bleeding). Adequate tiss ue perfusion ( \202 ow and pressure). Prophylactic drug therapy (proton pump inhibitor, H2 antagonist) decreases the incidence of stress ulceration though this is largely based on h istoric data when gut hypoperfusion was more prevalent. Patients at highest risk for stress ulcers are those requiring prolonged mechanical ventilation or with a concurrent coagulopa thy. \200 Treatment of major hemorrhage \200 Fluid resuscitation with colloid and blood, with blood products as appropriate to correct a ny coagulopathy. Maintain Hb >7 \200\22310g/dL and have adequate crossmatched blood availab le should further large hemorrhages occur. If possible, discontinue any ongoing anticoagula tion, e.g. heparin. Urgent diagnostic \201 breoptic endoscopy. Local injection of epineph rine or a sclerosant into (or thermal sealing of) a bleeding peptic ulcer base may halt fur ther bleeding. Banding or sclerosant injection may arrest bleeding varices. If oesophageal varices are known or highly suspected, consider vasopressin or terlipressin 9 a Sengstaken- type tube for severe hemorrhage, either as a bridge to endoscopy or if banding/injection is unsuccessful. Remember that sources of bleeding other than varices may be present, e.g. pe ptic ulcer. For peptic ulceration and generalized in \202 ammation, commence H2 antagonist or proton pump inhibitor. Give IV to ensure effect. Enteral antacid may also be bene \201 cial. For continued bleeding, contact interventional radiologist with view to angiographic embolisation. Surgery is now rarely necessary, but should be considered if bleeding contin ues, e.g. >6 \200\22310 unit transfusion need and embolisation is not available or fails. I nform surgeon of any patient with major bleeding. \200 UPPER GASTROINTESTINAL hemorrhage 413 See also: Sengstaken-type tube, p118; Full blood count, p220; Coagulation monitoring, p222; Colloids, p246; Blood transfusion, p248; Blood products, p250; H2 blockers and proton pump inhibitors, p286; Sucralfate, p288; Antacids, p290; Basic resuscitation, p338; Bleeding va rices, p414. 414 CHAPTER 25 Gastrointestinal disorders Bleeding varices Varices develop following a prolonged period of portal hypertension, usual ly related to liver cirrhosis. Approximately one third will bleed. They are commonly found in the lower esophagus, but occasionally in the stomach or duodenum. Torrential hemorrhage may occur. Approximately 50% of patients die within six weeks of presentation of their \201 rst bleed; each subsequent bleed carries a 30% mortality. Management 1. If airway and/or breathing are compromised, perform endotracheal intubation a nd institute mechanical ventilation. This facilitates Sengstaken- type tube placement and e ndoscopy though may be associated with severe hypotension secondary to covert hypovolaemia. If possible, en- sure adequate intravascular \201 lling before intubation. 2. Fluid resuscitation with colloid and blood with blood products as ap- propriate to corre ct any coagulopathy. Ensure good venous access (at least two 14G cannulae). Group-speci \201 c or O-negative blood may be needed for emergency use. Maintain Hb >7 \200\22310g/dL a nd have at least four units of crossmatched blood available for urgent transfusion. There i s a theoretical risk that over-transfusion may precipitate further bleeding by raising port al venous pressure. Cardiac output monitoring should be considered if the patient remains h aemodynamically unstable or there is a history of heart disease. 3. If bleeding is torrential, insert a Sengstaken-type tube and commence administration of IV vasopressin/terlipressin (q.v.). 4. Gentle placement of a large-bore nasogastric tube is a reasonably safe procedure that fa cilitates drainage of blood, lessens the risk of aspira- tion, and can be used to assess co ntinuing blood loss. 5. Perform urgent \201 breoptic endoscopy to exclude other sources of bleeding. This also allows variceal banding or local injection of scleros- ing agent. Bleeding is arrested in approximately 90% of cases. Endoscopy may be impossible if bleeding is too severe, and may have to be delayed for 6 \200\22324h until a period of tamponade by the Sengstaken-type tub e 9 vasopressin has enabled some control of the bleeding. 6. Either vasopressin, terlipressin, or octreotide can be administered for severe bleeding or prophylaxis against fresh bleeding. Vasopressin con- trols bleeding in approximately 60% of cases and its ef \201 cacy and safety appears to be enhanced by concurrent GTN. The si de effect pro \201 le of terlipressin is lower as it does not appear to precipitate as muc h me- senteric, cardiac, or digital ischaemia. Octreotide is a somatostatin ana- logue, but longer-acting than its parent compound; like somatostatin, it is probably as effective as vasopressin but without the side effects. 7. If bleeding continues after prolonged balloon tamponade (2 \200\2233 days) and repeated endoscopy, consider transjugular intrahepatic por tosys- temic stented shunt (TIPSS). This can be performed quickly and carries a relatively low mortality compared to surgery although the risk of encephalopathy is increased. 8. The traditional alternative to TIPSS is oesophageal transection (now performed with a st aple gun) with or without devascularisation. Mortality in the acute situation is of the ord er of 30%. BLEEDING VARICES 415 Drug dosages Octreotide 50mcg bolus, then 50mcg/h infusion Vasopressin 20 units over 20min, then 0.4 units/min infusion Also give glyceryl trinitrate 2 \200\22320mg/h to counteract myocardial and mesenteric isch aemia. Terlipressin 2 mg IV, followed by 1 \200\2232mg IV 4 \200\2236 hourly until bleeding controlled for up t o 72h See also: Sengstaken-type tube, p118; Upper gastrointestinal endoscopy, p120; Full blood co unt, p220; Coagulation monitoring, p222; Colloids, p246; Blood transfusion, p248; Blood pro ducts, p250; H2 blockers and proton pump inhibitors, p286; Basic resuscitation, p338; Upper gastrointestinal hemorrhage, p412; Acute liver failure, p430; Hepatic encephalopathy, p432 . 416 CHAPTER 25 Gastrointestinal disorders Oesophageal perforation Causes \200 Iatrogenic \200\224typically as a complication of endoscopy, placement of a feeding tube, o r surgery. This accounts for 85 \200\22390% of cases. Boerhaave \200\231s syndrome \200\224 oesophageal rupture related to forceful vomiting or, rarely, forceful coughing or obstructi on by food. External trauma (usually penetrating injuries). Corrosive liquids. \200 Diagnosis \200 Chest X-ray showing mediastinal emphysema and widening due to oedema. CT scan. Gastrogra \201 n swallow. \200 Complications \200 \200 \200 \200 Pneumomediastinum. Mediastinitis. Sepsis. High mortality, especially with late diagnosis. Management \200 \200 \200 Immediate antibiotic therapy. Intravascular volume replacement. Surgical repair of the perf oration (9 oesophageal exclusion and cervical oesophagostomy). Surgery must be performed wi thin 24h before tissues become too friable. Mediastinal drains are usually placed. Successf ul thoracoscopic closure is reported. In selected cases, the patient may be managed conserv atively. Nil by mouth and parenteral nutrition for several weeks. Analgesia. \200 \200 \200 OESOPHAGEAL PERFORATION 417 See alo: Upper gastrointestinal endoscopy, p120; Enteral feeding and drainage tubes, p122; Parenteral nutri- tion, p130; Antimicrobials, p326; Basic resuscitation, p338; Fluid challe nge, p342; Systemic in \202 amma- tion/multi-organ failure \200\224causes, p556; Sepsis a nd septic shock \200\224treatment, p560; Multiple trauma (1), p582; Multiple trauma (2), p5 84. 418 CHAPTER 25 Gastrointestinal disorders Intra-abdominal bowel perforation and obstruction Patients with bowel perforation or obstru ction may be admitted to the ICU after surgery, for preoperative resuscitation, and cardior espiratory optimization, or for conservative management. Although rarely occurring de novo in the ICU patient, these conditions may be dif \201 cult to diagnose because of sedation 9 muscle relaxation. Consider when there is: \200 \200 \200 \200 \200 \200 Abdominal pain, tenderness, peritonism. Abdominal distension. Agitation. Increased nasogast ric aspirates, vomiting. Increasing metabolic acidosis. Signs of hypovolaemia or sepsis. A \201 rm diagnosis may not be made until laparotomy, although supine and either erect or lateral abdominal X-ray may reveal either free gas in the peritoneum (perforation) or dila ted bowel loops with multiple \202 uid levels (obstruction). Ultrasound is usually unhelp ful though fecal \202 uid may occasionally be aspirated from the peritoneum following per foration. CT may identify the site of perforation or obstruction. It may be dif \201 cult to distinguish bowel obstruction from a paralytic ileus as: (i) bo wel sounds may be present or absent in either, and (ii) X-ray and CT appearances may be sim ilar. Management 1. Correct \202 uid and electrolyte abnormalities. Resuscitation should be pro mpt and aggressive and usually consists of colloid replacement plus blood to maintain Hb >7 \200\22310g/dL. Inotropes or vasopressors may be required to restore an adequate circulati on, particularly following per- foration. Cardiac output monitoring should be considered if circulatory status remains unstable or vasoactive drugs are required. 2. The surgeon should be informed at an early stage. A conservative ap- proach may be adopt ed, e.g. with upper small bowel perforation; how- ever, surgery is usually required for lar ge bowel perforation. Small or large bowel obstruction may sometimes be managed conservativ ely as sponta- neous resolution may occur, e.g. adhesions. Prompt surgical exploration shou ld be encouraged if the patient shows signs of systemic toxicity. 3. Both conservative and post-operative management of perforation and obstruction usually require continuous nasogas tric drainage to decom- press the stomach, nil by mouth, and parenteral nutrition. 4. Pain relief should not be withheld. 5. Broad-spectrum antibiotic therapy should be start ed for bowel per- foration after appropriate specimens have been taken for laboratory analy sis. Therapy usually comprises aerobic and anaerobic Gram-negative cover (e.g. 2nd/3rd gene ration cephalosporin, quinolone or carbapenem, plus metronidazole 9 aminoglycoside). 6. Post-operative management of bowel perforation may involve repeated laparotomies to excl ude collections of pus and bowel ischaemia/infarc- tion; surgery should be expedited if the patient \200\231s condition deterio- rates. Alternatively, regular ultrasonographic and/or CT examinations with percutaneous drainage may be adopted. INTRA-ABDOMINAL BOWEL PERFORATION AND OBSTRUCTION 419 See also: Upper gastrointestinal endoscopy, p120; Enteral feeding and drainage tubes, p122; Parenteral nutrition, p130; Electrolytes (Na+, K+, Cl \200\223, HCO3 \200\223), p212; Ant imicrobials, p326; Basic resuscitation, p338; Fluid challenge, p342; Abdominal sepsis, p422 ; Metabolic acidosis, p502; Systemic in \202 amma- tion/multi-organ failure \200\224causes , p556; Sepsis and septic shock \200\224treatment, p560; Raised intra- abdominal pressure, p614; Post-operative critical care, p616. 420 CHAPTER 25 Gastrointestinal disorders Lower intestinal bleeding and colitis Causes of lower gastrointestinal bleeding \200 \200 \200 \200 \200 \200 Bowel ischaemia/infarction. In \202 ammatory bowel disease (ulcerative colitis, Crohn \200 \231s disease). Infection, e.g. Shigella, Campylobacter, amoebic dysentery. Upper gastroint estinal source, e.g. peptic ulceration. Angiodysplasia. Neoplasm. Although relatively rare, massive lower gastrointestinal hemorrhage can be life-threatening . Ischaemic/infarcted bowel Can occur following prolonged hypoperfusion or, occasionally, sec ondary to a mesenteric embolus. It usually presents with severe abdominal pain, bloody diar rhea, and signs of systemic toxicity, including a rapidly increasing metabolic acidosis. Pl asma phosphate levels may be elevated. CT or X-ray appearances of thickened, oedematous bow el loops ( \200\230thumb- printing \200\231) with an increased distance between bowel loops are sugges- tive. Treatment is by restoration of tissue perfusion, blood transfusion to ma intain Hb >7 \200\22310g/dL and, if clinical features fail to settle promptly, laparotomy w ith a view to bowel excision. In \202 ammatory bowel disease Presents with weight loss, abdominal pain, and diarrhea tha t usually con- tains blood. Complications of ulcerative colitis include perforation and tox ic megacolon while complications of Crohn \200\231s disease include \201 stulae, abscesse s, and perforations. Management involves: 1. Fluid and electrolyte replacement. 2. Blood tr ansfusion to maintain Hb >7 \200\22310g/dL. 3. High-dose corticosteroids IV and, if distal bowel involvement, by enema. 4. Nutrition (often parenteral). 5. Regular surgical review. Surgery may be indicated if sy mptoms fail to settle after 5 \200\2237 days, or for toxic megacolon, perforation, abscesse s, or obstruction. 6. Antidiarrhoeal drugs should be avoided. Angiodysplasia Usually presents as fresh bleeding per rectum and this may be consider- able . It is due to an arterio-venous malformation and is more common in the elderly. Localizati on and embolisation by angiography may be curative during active bleeding, Surgery may be r equired if bleeding fails to settle on conservative management and, occasionally, \200\230 blind \200\231 laparoscopic embol- isation of a mesenteric vessel. However, localization of the lesion may be dif \201 cult at laparotomy, necessitating extensive bowel resection. LOWER INTESTINAL BLEEDING AND COLITIS 421 See also: Full blood count, p220; Coagulation monitoring, p222; Bacteriology, p224; Virolog y, serology and assays, p226; Colloids, p246; Blood transfusion, p248; Blood products, p250 ; Antimicrobials, p326; Basic resuscitation, p338; Diarrhea, p408; Abdominal sepsis, p422. 422 CHAPTER 25 Gastrointestinal disorders Abdominal sepsis This is a common but dif \201 cult to diagnose condition in the ICU patie nt. A proportion of such patients are admitted following laparotomy, but others may develop abdominal sepsis de novo or as a secondary compli- cation following abdominal surgery, in particular after bowel resection. Sepsis may either be localized to an organ, e.g. cholecys titis, or the peri- toneal cavity (abscess); alternatively, there may be a generalized peri to- nitis. Non-bowel infection or in \202 ammation can present in a similar manner, e.g. p ancreatitis, cholecystitis, gynecological infection, pyelonephritis. Clinical features \200 Non-speci \201 c signs, including pyrexia (especially swinging), neutrophilia, falling pla telets, increasing metabolic acidosis, circulatory instability. Abdominal distension 9 loca lized discomfort, peritonism. Abdominal mass, e.g. gallbladder, pseudocyst, abscess. Failur e to tolerate enteral feed/large nasogastric aspirates. Pleural effusion (if subdiaphragmat ic sepsis). Diarrhea (if pelvic sepsis). \200 \200 \200 \200 Diagnosis \200 \200 \200 Ultrasound. CT scan. Laparotomy. Samples should be taken for microbiological analysis from blood, urine, stool, abdominal dr ain \202 uid, and vaginal discharge if present. A sample of pus is preferred to a swab. H yperamylasaemia may suggest pancreatitis though levels can be elevated with other intra-abd ominal pathologies. Treatment \200 Antibiotic therapy providing aerobic and anaerobic Gram-negative cover (e.g. 2nd or 3rd gen eration cephalosporin, quinolone or carbapenem, plus metronidazole 9 aminoglycoside). Treat ment can be modi \201 ed depending on culture results and patient response. Ultrasonic or CT-guided drainage of pus. Laparotomy with removal of pus, peritoneal lavage, etc. \200 A negative laparotomy should be viewed as a useful means of excluding intra-abdominal sepsi s rather than an unnecessary procedure. Laparotomy should be encouraged if the patient dete riorates and a high suspicion of abdominal pathology persists. Cholecystitis, with or without (acalculous) the presence of gallstones, may present with si gns of infection. There is a characteristic ultrasound and CT appearance of an enlarged org an with a thickened, oedematous wall surrounded by \202 uid. Treatment is often conservat ive with antibiotics (as above) and percutaneous, ultrasound-guided drainage via a pigtail cath- eter. Cholecystectomy is rarely necessary in the acute situation unless the gallbladd er has perforated, though some authorities argue that this is the treatment of choice for a calculous cholecystitis. ABDOMINAL SEPSIS 423 See also: Enteral feeding and drainage tubes, p122; Electrolytes (Na+, K+, Cl \200\223, HCO 3 \200\223), p212; Full blood count, p220; Bacteriology, p224; Virology, serology, and ass ays, p226; Antimicrobials, p326; Basic resuscitation, p338; Fluid challenge, p342; Vomiting /gastric stasis, p406; Diarrhea, p408; Failure to open bowels, p410; Intra-abdominal bowel perforation and obstruction, p418; Pancreatitis, p424; Systemic in \202 ammation/multi-org an failure \200\224causes, p556; Sepsis and septic shock \200\224treatment, p560; Post-oper ative critical care, p620. 424 CHAPTER 25 Gastrointestinal disorders Pancreatitis The in \202 amed pancreas and surrounding retroperitoneal tissues may range f rom mildly oedematous to haemorrhagic and necrotising. A pseudocyst may develop which can b ecome infected, and the bile duct may be obstructed causing biliary obstruction and jaundic e. Though overall mortality is quoted at 5 \200\22310%, this is much higher (approximately 40%) in those with severe pan- creatitis requiring intensive care. Pancreatitis is severe i f APACHE II score >8. Causes \200 \200 \200 \200 Alcohol. Gallstones. Miscellaneous, e.g. ischaemia, trauma, viral, hyperlipidaemia. Part of the multiple organ failure syndrome. Diagnosis \200 Non-speci \201 c features include central, severe abdominal pain, pyrexia, haemodynamic in stability, vomiting, ileus. Discoloration around the umbilicus (Cullen \200\231s sign) or \202 anks (Gray Turner \200\231s sign) is rarely seen. Plasma enzymes \200\224elevated lev els of amylase (usually >1000IU/mL), and pancreatic lipase are suggestive but non-speci \201 c. The levels may be normal, even in severe pancreatitis. Ultrasound. CT scan. Laparot omy. \200 \200 Complications \200 \200 \200 \200 \200 Multi-organ dysfunction syndrome. Infection/abscess formation. Occasional massive bleeding from erosion of local artery or vein. Hypocalcaemia. Diabetes mellitus. Management \200 General measures, including \202 uid resuscitation, blood transfusion to maintain Hb 7 \200\22310g/dL, respiratory support, analgesia, and anti-emetics. Routine antibiotic prophy laxis is no longer recommended. Adequate monitoring should be instituted, including pulmona ry artery catheterisation if cardiorespiratory instability is present. The patient is tradi tionally kept nil by mouth with continuous nasogastric drainage, and nutrition and vitamins provided parenterally. However, recent studies show safety and ef \201 cacy of distal nas ojejunal (or even nasogastric) enteral feeding. Relieve gallstone obstruction either endosc opically or surgically. Hypocalcaemia, if symptomatic, should be treated by intermittent sl ow IV injection (or occasionally, infusion) of 10% calcium chloride. Hyperglycaemia should be controlled by continuous IV insulin infusion. The role of surgery is controversial; advo cates promote either a conservative approach with percutaneous drainage of infected and/or necrotic debris, or an aggressive, interventional strategy with regular (often daily) lapar otomy for debridement and peritoneal lavage. Pseudocysts may resolve, or need drainage perc utaneously or into the bowel. Probiotic therapy for pancreatitis is associated with worse o utcomes. \200 \200 PANCREATITIS 425 Ranson \200\231s signs of severity in acute pancreatitis On hospital admission Age >55 years old Blood glucose >11mmol/L Serum LDH >300U/L Serum AST >250U/L White blood count >16x109/L At 48h after admission Haematocrit fall >10% Blood urea rise >1mmol/L Serum calcium <2mmol/ L PaO2 <8kPa Arterial base de \201 cit >4mmol/L Estimated \202 uid sequestration >6L Pancreatitis severe if \211 2 criteria met within 48h of admission. CT severity index Element Finding Normal pancreas Pancreatic enlargement In \202 ammation of pancreas and peripancre atic fat Single \202 uid collection or phlegmon \211 2 \202 uid collections or phlegmo ns No necrosis Necrosis of one third of pancreas Necrosis of one half of the pancreas Necro sis of > one half of the pancreas Points 0 1 2 3 4 0 2 4 6 Grade of acute pancreatitis Degree of pancreatic necrosis Add points for grade of acute pancreatitis + degree of pancreatic necrosis. Severity index 0 \200\2231 2 \200\2233 4 \200\2236 7 \200\22310 Mortality 0% 3% 6% 17% Complications 0% 8% 35% 92% Pancreatitis Outcome Prediction (POP) score Score 0 1 2 3 4 5 6 7 8 10 16 \200\22329 Age \211 90 MAP PaO2/FIO2 \211 30 Arterial pH >7.35 30 \200\22339 80 \200\22389 40 \200\22349 60 \200\22379 10 \200\22329.9 <10 50 \200\22359 60 \200\22369 \211 70 <40 50 \200\22359 40 \200\22349 7.30 \200\2237.35 7.25 \200\223 7.29 7.20 \200\223 7.24 11 \200\22316.9 <1.6 or 2.5 7.10 \200\223 7.19 7.00 \200\223 7.09 \211 17 < 7 Urea Total serum calcium <5 2.0 \200\2232.29 1.8 \200\2231.99 5 \200\2237.9 8 \200\22310.9 1.6 \200\2231.79 or 2.3 \200\2232.49 Key paper Harrison DA, D \200\231Amico G, Singer M. (2007) The Pancreatitis Outcome Predict ion (POP) Score: a new prognostic index for patients with severe acute pancreatitis. Crit C are Med 35: 1703 \200\2238 See also: APACHE score, p28; Enteral nutrition, p128; Parenteral nutrition, p130; Basic res uscitation, p338; Abdominal sepsis, p422; Hypocalcaemia, p496; Systemic in \202 ammation/m ulti-organ failure \200\224causes, p556; Sepsis and septic shock \200\224treatment, p560. This page intentionally left blank 427 Chapter 26 Hepatic disorders Jaundice 428 Acute liver failure 430 Hepatic encephalopathy 432 Chronic liver failure 434 428 CHAPTER 26 Hepatic disorders Jaundice Jaundice is a clinical diagnosis of yellow pigmentation of sclera and skin resulti ng from a raised plasma bilirubin. It is usually visible when the plasma bilirubin exceeds 30 \200\22340 mol/L. Common causes seen in the ICU \200 Pre-hepatic \200\224intravascular haemolysis (e.g. drugs, malaria, haemolytic uraemic syndr ome), Gilbert \200\231s syndrome. Hepatocellular \200\224critical illness, viral (hepatitis A, B, C, Epstein \200\223Barr), alcohol, drugs (e.g. paracetamol, halothane), toxoplasmosi s, leptospirosis. Cholestatic \200\224critical illness, intrahepatic causes (e.g. drugs suc h as chlorpromazine, erythromycin and isoniazid, primary biliary cirrhosis), extrahepatic c auses (e.g. biliary obstruction by gallstones, neoplasm, pancreatitis). Diagnosis \200 \200 Urinalysis \200\224unconjugated bilirubin does not appear in the urine. Measurement of conj ugated and unconjugated bilirubin \200\224conjugated bilirubin predominates in cholestatic jaundice, unconjugated bilirubin in pre-hepatic jaundice; a mixed picture is often seen in hepatocellular jaundice. Plasma alkaline phosphatase is usually markedly elevated in obstru ctive jaundice while prothrombin times, aspartate transaminase, and alanine aminotransferas e are elevated in hepatocellular jaundice. Ultrasound or CT scan will diagnose extrahepatic biliary obstruction. Management 1. Identify and treat cause. Where possible, discontinue any drug that could be implicated. If extrahepatic, consider percutaneous trans-hepatic drainage (under radiology guidance), ERCP 9 bile duct stenting or, rarely, surgery. 2. Liver biopsy is rarely necessary in a jaundiced ICU patient unless the diagnosis is unkn own and the possibility exists of liver involvement in the underlying pathology, e.g. malig nancy. 3. Non-obstructive jaundice usually settles with conservative manage- ment as the patient recovers. 4. An antihistamine and topical calamine lotion may provide symptomatic relief for pruritus if troublesome. Colestyramine 4g tds PO may be helpful in obstructive jaundice. JAUNDICE 429 See also: Liver function tests, p218; Coagulation monitoring, p222; Acute liver failure, p4 30; Chronic liver failure, p434; Haemolysis, p476. 430 CHAPTER 26 Hepatic disorders Acute liver failure This results from massive damage to liver cells leading to severe liver dys- function and encephalopathy. Survival rates for liver failure with grade 3 or 4 hepat ic encephalopathy vary from 10 \200\22340% on medical therapy alone to 60 \200\22380% with orthotopic liver transplantation. Major causes \200 \200 \200 \200 \200 Alcohol. Drugs, particularly paracetamol overdose. Viral hepatitis, particularly hepatitis B, hepatitis C. Poisons, e.g. carbon tetrachloride. Decompensation of chronic disease, e.g. infection or variceal bleed. Diagnosis \200 Consider in any patient presenting with jaundice: generalized bleeding, encephalopathy, or marked hypoglycaemia. Prolonged PT or INR and hyperbilirubinaemia. In severe liver failure, plasma enzyme levels may not be elevated. Management \200 General measures include \202 uid resuscitation and blood transfusion to keep Hb 7 \200 \22310g/dL. The circulation is usually hyperdynamic and dilated; vasopressors may be needed to maintain an adequate BP. Correct coagulopathy in patients who are bleeding or about to undergo an invasive procedure. Otherwise, withhold as this provides a good guide to recover y or the need for transplantation. Institute adequate monitoring for cardiorespiratory inst ability. Mechanical ventilation may be necessary for airway protection (e.g. encephalopathy , variceal bleed) or respiratory failure (e.g. lung shunts \200\224hepatopulmonary syndrome in cirrhotics). Infection is common and may be Gram-positive, Gram-negative, or fungal. Cl inical signs are often lacking. Samples of blood, sputum, urine, wound and catheter site sw abs, drain \202 uid, and ascites should be sent for regular microbiological surveillance. Ascitic white blood count >250/hpf suggests spontaneous bacterial peritonitis. Systemic an timicrobial 9 antifungal prophylaxis is often used to reduce infection rates, though con \201 rmatory multicentre trial data are lacking. Monitor closely for hypoglycaemia. Treat w ith enteral (or parenteral) nutrition or 10 \200\22350% glucose infusion to maintain normog lycaemia. Renal failure occurs in 30 \200\22370% of cases. The incidence may be reduced by careful maintenance of intravascular volume. Vasopressin/terlipressin can be used to mainta in urine output in hepatorenal syndrome. Upper gastrointestinal bleeding is common. Prophyl actic H2-blockers or proton pump inhibitors are routinely given. N-acetylcysteine increases transplant free survival in early stage acute liver failure. Extracorporeal systems that b ind circulating toxins via albumin dialysis (e.g. MARS \200\224Molecular Adsorbent Recircul ation System) or adsorption columns (fractionated plasma separation and adsorption, charcoa l haemoperfusion) have yet to show outcome bene \201 t. Corticosteroid therapy is used in selected cases (e.g. alcoholic hepatitis) when bleeding and infection are absent. \200 ACUTE LIVER FAILURE 431 Drug dosages N-acetylcysteine Loading dose 150mg/kg IV infused over 1h diluted in 250mL 5% glucose First maintenance dose 50mg/kg IV infused over 4h diluted in 500mL 5% glucose Second maintenance dose 100mg/kg IV infused over 16h dilute in 1000mL 5% glucose Continuing treatment Consider 150mg/kg over 24h until liver failure improves or transplant. Each infusion immediately follows the previous; total treatment time 21h). See also: Liver function tests, p218; Coagulation monitoring, p222; Lactate, p234; Acute re nal failure \200\224 diagnosis, p400; Acute renal failure \200\224management, p402; Hepatic encephalopathy, p432; Chronic liver failure, p434; Hypoglycaemia, p506; Paracetamol poison ing, p524; Infection \200\224diagnosis, p552; Infection \200\224treatment, p554. 432 CHAPTER 26 Hepatic disorders Hepatic encephalopathy Grading 1. Confused, altered mood. 2. Inappropriate, drowsy. 3. Stup orose but rousable, very confused, agitated. 4. Coma, unresponsive to painful stimuli. The risk of cerebral oedema is far higher at grades 3 and 4 (50 \200\22385%). Suggestive si gns include systemic hypertension, progressive bradycardia, and increasing muscle rigidity at ICP >30mmHg. Management \200 Correct/avoid potential aggravating factors, e.g. gut hemorrhage, over- sedation, hypoxia, hypoglycaemia, infection, electrolyte imbalance. Consider (ICP) monitoring. CT and clinical features correlate poorly with ICP though no controlled studies have yet been performed to show outcome bene \201 t from ICP monitoring which carries its own complication rate (ble eding, infection). Maintain patient in slight head-up position (20 \200\22330*). Regular la ctulose, e.g. 20 \200\22330mL qds PO, to achieve 2 \200\2233 bowel motions/ day. Dietary re striction of protein is now not encouraged as this promotes endogenous protein utilization. Hyperventilation to achieve a PaCO2 of 3.5 \200\2234kPa is no longer recommended. It may a lso compromise cerebral blood \202 ow. Give mannitol (0.5 \200\2231mg/kg over 20 \200\223 30min) if serum osmolality <320mOsm/kg and either a raised ICP or clinical signs of cerebra l oedema persist. If severe renal dysfunction is present, use renal replacement therapy in conjunction with mannitol. Consider maintaining Na+ 145 \200\223155mmol/L. Sodium benzoate (2g tds PO) may be considered if the patient is severely hyperammonaemic. If still no respo nse, consider possibility of liver transplantation. Exercise caution with concomitant drug usage. \200 \200 Identi \201 cation of patients unlikely to survive without transplantation \200 Prothrom bin time >100s. Or any three of the following: \200 \200 Age <10 or >40y. Etiology is seronegative hepatitis, Wilson \200\231s disease, halothane, o r other drug reaction. Duration of jaundice pre-encephalopathy >7d. Prothrombin time >50s. Serum bilirubin >300 mol/L. \200 \200 If paracetamol-induced: \200 pH <7.3 or prothrombin time >100s and creatinine >200 mol/L plus grade 3 or 4 encephalopat hy. As only 50 \200\22385% of patients identi \201 ed as requiring transplantation will surviv e long enough to receive one, the regional Liver Unit should be informed soon after diagnos is of all possible candidates. HEPATIC ENCEPHALOPATHY 433 See also: Intracranial pressure monitoring, p200; Electrolytes (Na+, K+, Cl \200\223, HCO3 \200\223), p212; Liver function tests, p218; Coagulation monitoring, p222; Upper gastroint estinal hemorrhage, p412; Bleeding varices, p414; Acute liver failure, p430; Coma, p438; Ra ised intracranial pressure, p454. 434 CHAPTER 26 Hepatic disorders Chronic liver failure Patients admitted to intensive care with chronic liver failure may de velop speci \201 c associated problems: \200 Acute decompensation \200\224may be secondary to infection, sedation, hypovolaemia, hypoten sion, diuretics, gastrointestinal hemorrhage, excess dietary protein, and electrolyte imbal ance. Infection \200\224the patient may transmit infection, e.g. hepatitis A, B, or C, and by being immunosuppressed, is also more prone to acquiring infections (including TB and fun gi). Drug metabolism \200\224many drugs are metabolized in whole or in part by the liver an d/or excreted into the bile. Drug actions may be prolonged or slowed depending on whether t he metabolites are active or not. In particular, sedatives may have a greatly prolonged dur ation of action. Portal hypertension \200\224results in ascites, varices, and splenomegaly. Ascites may produce diaphragmatic splinting and may become infected. Drainage may incur a considerable protein loss. Varices may bleed while splenomegaly may result in thrombocytopa enia. Renal failure may occur from high intra-abdominal pressure (or hepatorenal syndrome). Bleeding \200\224increased risk due to reduced production of clotting factors (II, VII, IX , X), varices, and splenomegaly-related thrombocytopaenia. Alcohol \200\224the most frequen t cause of cirrhosis in the western world, acute withdrawal may lead to delirium tremens wi th severe agitation, hallucinations, seizures, and cardiovascular disturbances. 2* hyperald osteronism \200\224results in oliguria, salt and water retention. Increased tendency to jau ndice, especially during critical illness. \200 Management 1. Ascites. \200 Take specimens for microbiological analysis (including TB), protein, and cytology. If WBC > 250/hpf, give antibiotic cover (particularly covering Gram-negative bacteria). If present i n large quantity: (i) decrease sodium and water intake, (ii) commence spironolactone PO (or potassium canrenoate IV) 9 furosemide. Paracentesis 9 colloid replacement or ascitic reinf usion (if uninfected/non-pancreatitic in origin) may be considered, particularly if diaphra gmatic splinting occurs. 2. Coagulopathy. \200 \200 3. Hypoglycaemia \200\224should be prevented by adequate nut rition or 10% or Vitamin K 10mg/day slow IV bolus for 2 \200\2233 days. Fresh frozen plasma, platelets as ne cessary. 20% glucose infusion. 4. Adequate nutrition and vitamin supplementation. As patients are often malnourished and at risk of beriberi, thiamine should be given. 5. Acute decompensation \200\224avoid any precipitating causes, e.g. infection, sedation, hypovolaemia, electrolyte imbalance. 6. Drug administration \200\224review type and dose regularly. CHRONIC LIVER FAILURE 435 See also: Liver function tests, p218; Coagulation monitoring, p222; Virology, serology, and assays, p226; Acute liver failure, p430; Hypoglycaemia, p506.