Non-pulmonary Critical Care - part 5 pdf

risks of rebleeding, although the data to support such an approach are weak at best. In those with well-preserved liver function, a surgical shunt can also provide long- term relief from bleeding. 146 Portal Hypertensive Gastropathy Portal hypertensive gastropathy (PHG) is a manifes- tation of portal hypertension. Endoscopically it is characterized by a mosaic mucosal pattern with varying degrees of submucosal hemorrhage. It is often asymp- tomatic but may lead to ch ronic transfusion–requiring blood loss or acute bleeding (rarely). Although portal gastropathy is more often seen in the setting of gastro- esophageal varices, its severity does not correlate with portal pressure. Nevertheless, bleeding is often amelio- rated by reduction of portal pressure. Both octreotide and nonselective b-blockade can be helpful in decreas- ing acute bleeding and the degree of rebleeding from PHG via reduction of portal blood flow. 147–149 In refractory cases, TIPS can be effective at reducing transfusion requirements. 150 THERAPIES TO ACHIEVE HEMOSTASIS Drug Therapy Drug therapy is an integral component of the manage- ment of acute portal hypertensive hemorrhage and should be started on presentation. To optimize the effectiveness of drug or endoscopic therapy, clotting abnormalities must be corrected. Target INR and platelet count should be 1.5 and 75, respectively. In the setting of renal failure platelets may be dysfunc- tional and DDAVP (Desamino-D-Arginine Vasopres- sin) should be considered. FFP alone or in combination with rFVIIa can be given to rapidly correct coagulop- athy. A recent randomized, clinical trial showed that whengiveninadditiontostandardtherapy,100mg/kg of rFVIIa may improve control of bleeding in patients with advanced cirrhosis. 151 Somatostatin or octreotide, its synthetic analogue, stops acute bleeding from varices in 80% of cases. 152 It does so through a reduction of portal pressure via effects on vasoactive peptides or through the prevention of postprandial hyperemia (blood meal). Octreotide has an excellent safety profile and can be given initially as a subcutaneous bolus of 50 to 100 mg followed by a continuous infusion of 50 mg/h for 3 to 5 days. Although it does decrease portal pressure acutely, these effects appear to be short lived due to rapid tachyphylaxis. 153 Nevertheless, studies have shown a significant decrease in rebleeding after endoscopic therapy in those receiving octreotide infusion. 154,155 Vasopressin reduces splanchnic blood flow in addition to portal pressure. It is effective in controlling variceal hemorrhage; however, its use is limited due to systemic effects such as coronary and mesenteric ische- mia. 156 If vasopressin is used in conjunction with nitro- glycerin, these effects can be minimized. 157,158 Terlipressin is a synthetic analogue of vasopressin with a longer half-life and fewer side effects. It is effective in the treatment of acute variceal bleeding with or without endoscopic therapy and has been shown to reduce mortality. 125,159 It appears to be as effective as vasopressin or endoscopic treatment 126,160 in controlling acute variceal hemorrhage, but is not yet available in the United States. Endoscopic Therapy Endoscopic variceal band ligation (EBL) is currently the preferred endoscopic technique for the management of esophageal varices. It is at least as effective as endoscopic sclerotherapy (EST) but has a superior safety profile and lower complication rate. 133,161,162 EBL also decreases the incidence of bleeding, when given as primary pro- phylaxis, 163,164 and death 165 from variceal bleeding. Band ligation leads to strangulation and subsequent obliteration of the banded varix. EST involves the injection of a sclerosant (sodium morrhuate, ethanolamine, or polidocanol) into or around a varix. This leads to coagulative necrosis and obliter- ation of varices in the vicinity of the injection. Compli- cations related to EST tend to occur more frequently and be more severe than with EBL and include esophageal ulceration, stricturing, esophageal perforation, pleural effusion, and sepsis. Despite a higher complication rate, a role st ill exists for EST. It can be a useful adjunct to EBL in the setting of massive hemorrhage with poor visibility because the location of injection need not be as precise to achieve hemostasis. Regardless of the choice of endoscopic manage- ment for acute bleeding, follow-up endoscopy within 1 to 2 weeks for further banding is essential to decrease the risk of rebleeding. EBL should then be continued in the future until variceal obliteration is achieved. Balloon Occlusion Balloon tamponade is effective in the 5 to 10% of patients in which hemostasis cannot be achieved acutely with medical or endoscopic therapy. It successfully stops bleeding from esophagogastric varices through external compression of varices, but rebleeding occurs in 50%. 166 Many types of tubes exist (Sengsten-Blake Tube, Warne Surgical Products, Ltd., Armagh, Ireland, UK; and Linton Tube, Bard Manufacturing, Covington, Geor- gia, USA) with mild variations; however, in most cases; inflation of the gastric balloon is adequate to stop variceal hemorrhage. It is quite effective as a bridge to more definitive therapy (TIPS or surgery) and cannot be INTENSIVE MANAGEMENT OF HEPATIC FAILURE/RINELLA, SANYAL 251 in place for more than 24 hours given the significant risk of esophageal necrosis and rupture. 167 Transjugular Intrahepatic Portosystemic Shunt (TIPS) TIPS involves placing a stent within the liver that bridges a branch of the intrahepatic hepatic vein with an intrahepatic branch of the portal vein, allowing diversion of blood flow away from the cirrhotic liver, decompressing portal pressures, and reducing the im- petus to bleed. In experienced hands TIPS is a very effective method for stopping acute hemorrhage from esophageal varices but can be less effective in gastric variceal bleeding. 168 In the setting of variceal bleeding, TIPS should be reserved for cases that are refractory to endoscopic therapy, 169 orinthecaseofgastricvarices, used in conjunction with embolization. If recurrent bleeding occurs in a patient with a TIPS in place, the most important intervention is interrogation of the TIPS to document and treat thrombosis or stenosis. Until recently, TIPS was complicated by fre- quent stenosis and thrombosis. 168 Polytetrafluoroethy- lene (PTFE)-coated stents have significantly improved stent patency and the need for reintervention. 170–172 Although they have not been directly compared with surgical shunts, these data suggest they offer comparable results. Surgery TIPS has significantly reduced the need for shunt surgery; however, surgery remains a good option in selected cases when TIPS is not technically feasible or fails or in patients with significant portal hypertension in the face of preserved hepatic synthetic function. The long-term patency rate of shunt surgery is thought to be superior to that of TIPS; however, newer coated stents may challenge this assumption. 170–172 Surgical alterna- tives for acute portal hypertensive hemorrhage include total or selective shunt surgery, devascularization proce- dures (Suguira or modification) or liver transplantation. If surgery is necessary, it is best done at a center with extensive experience. COMPLICATIONS ASSOCIATED WITH VARICEAL BLEEDING Hepatic Encephalopathy The initial approach to the patient with HE should focus on the identification and correction of any precipitant in addition to treatment of the encephalopathy. Common precipitants include gastrointestinal (GI) bleeding, medications, infection, dehydration, electrolyte distur- bances, constipation, excessive protein load, portosyste- mic shunting (TIPS or spontaneous), and worsening liver function (Table 5). Potential precipitants such as these must be individually considered and subsequently excluded. In the case of infection, spontaneous bacterial peritonitis (SBP) is the most common infection in this population and must be ruled out with a diagnostic paracentesis as already discussed. Often, HE is the only manifestation of SBP. TREATMENT OF HEPATIC ENCEPHALOPATHY Nonabsorbable disaccharides and antibiotics have been shown to modify gut flora and decrease blood ammonia levels, but these are not necessarily related (indicating nonbacterial sources of ammonia, which may also be decreased by these compounds). Lactulose is the first- line therapy for HE. It is most effective if given orally and titrated to a dose that achieves three to four soft bowel movements a day. A common mistake in the ICU is continued lactulose despite diarrhea in the encepha- lopathic patient. Not only will this not improve ence- phalopathy, it may worsen it through free water depletion. If the patient is having adequate bowel move- ments on lactulose, but continues to be confused, several agents can be added. Nonabsorbable antibiotics such as neomycin or rifaxamin are effective for the treatment of HE either alone or in conjunction with lactulose. Met- ronidazole is also efficacious; however, side effects limit prolonged use. Zinc is a cofactor for the urea cycle and can increase the clearance of ammonia. Zinc levels are decreased in patients with cirrh osis and HE. Supple- mentation with zinc sulfate 600 mg/d normalizes zinc levels, decreases ammonia, and improves HE. 173 Branched-chain amino acids have not convincingly shown improvement in HE; however, they may be considered in patients that are not receiving protein in any form. 174,175 When HE is refractory to medical treatment other possibilities must be entertained. In those with a TIPS, occlusion or narrowing of the stent lumen can improve mental status. 176,177 If no TIPS or surgical shunt is present, abdominal imaging should be obtained Table 5 Precipitants of Hepatic Encephalopathy Infection Gastrointestinal bleeding Medical noncompliance Medication—sedatives, narcotics, other Electrolyte disturbances Portosystemic shunting Transjugular intrahepatic portosystemic shunt Spontaneous Dehydration Excessive protein load Constipation Worsening liver function 252 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 to look for a prominent portosystemic collateral that could be radiographically embolized. 178 Infection Bacterial infections complicate 35 to 66% of cases of gastrointestinal bleeding in patients with AoCLF. 179–184 Not only is infection common after bleeding, it may also provoke rebleeding. 179 Furthermore, bacterial infection and the use of prophylactic antibiotics are independently associated with failure to control variceal hemorrhage in the first 5 days of admission. 180 Many randomized, controlled trials have shown that antibiotic prophylaxis targeted at enteric organisms (such as quinolones or third-generation cephalosporin) is effective in the pre- vention of postbleeding infection in cirrhotic patients. In addition, a meta-analysis of randomized, controlled trials concluded that antibiotic prophylaxis resulted in less infections and improved short-term survival in bleeding patients with cirrhosis. 185 Given these data, prophylactic systemic antibiotics should be given to cirrhotic patients with gastrointestinal hemor rhage. Spontaneous Bacterial Peritonitis SBP is a frequent and severe complication in those with cirrhosis and ascites. 186 It is associated with significant morbidity and mortality by precipitating renal failure in 30%, 187 worsening HE, and causing hemodynamic col- lapse in an already critically ill patient. The deterioration of renal function is the most sensitive predictor of in- hospital mortality. 187,188 Renal failure often results from a reduction in effective circulating blood volume, cyto- kine surges, and activation of the renin-angiotensin system precipitated by infection. 187,188 Bacterial trans- location from the gut is thought to be the most common mode of ascitic fluid inoculation. 189,190 Predisposing factors for the development of SBP include advanced liver disease, gastrointestinal bleeding, ascitic total pro- tein fluid content 1 g/dL and a previous history of SBP. 181,191–193 INTERPRETATION OF A DIAGNOSTIC PERITONEAL TAP It is crucial to have a very low threshold to perform a diagnostic paracentesis in the patient with suspected SBP. Ideally, this should be done prior to the initia- tion of antibiotics. Peritoneal fluid should be sent for cell count, culture, albumin, total protein, LDH (lactate dehydrogenase) and glucose. Blood culture bottles should be inoculated at the bedside to improve yield. SBP is defined as an ascitic fluid polymorphonu- clear (PMN) ! 250 cells/mm 3 , in the setting of a positive monomicrobial ascitic fluid culture. 194,195 Cul- ture positivity can fluctuate from one tap to the next; thus culture-negative neutrocytic ascites should be treated with antibiotics as previously outlined. 196 Monomicrobial non-neutrocytic bacterascites is another common variant of SBP. It is defined as a fluid cell count < 250 cells/ mm 3 with a positive cul ture. 197 Runyon and Hoefs and Chu et al found that 62 to 86% of cases of monomicrobial bacterial ascites resolve spon- taneously, and those that did not resolve were sympto- matic on presentation. 197,198 Thus, in a clinically stable asymptomatic patient, one could observe or consider repeat diagnostic paracentesis. However, in a critically ill patient with AoCLF in the ICU, antibiotic therapy may be the best course of action. TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS Patients should be given a non-nephrotoxic antibiotic with good enteric coverage such as a third-generation cephalosporin. Cefotaxime 2 g (q8h) is the best- studied antibiotic for the treatment of SBP. 199,200 Other antibiotics of comparable spectrum can be used and can be tailored if the organism is identified. Once the patient has been on antibiotics for 48 hours, a diagnostic tap must be repeated to assess response to treatment. If there is not a significant decrement in the white blood cell (WBC) count, antibiotic coverage should be broadened. Once treatment efficacy is estab- lished, antibiotics should be given for 5 days. 201 Intra- venous albumin is integral to the treatment of SBP andshouldbeusedinconjunctionwithantibiotics.It has been shown in a randomized, controlled trial to decrease the incidence of renal failure and subsequent mortality when compared with antibiotics alone. 202 Based on these data, albumin should be given at a dose of 1.5 mg/kg on day 1 and 1 mg/kg on day 3. A recent study compared albumin to plasma expansion with hydroxyethyl starch. Fernandez and colleagues Table 6 Diagnostic Criteria for Hepatorenal Syndrome (International Ascites Club) MAJOR Chronic or acute liver disease with advanced hepatic failure and portal hypetension Creatinine> 1.5mg/dLor24-hourcreatinineclearance< 40mL/min Absence of shock, ongoing infection, use of nephrotoxic drugs, gastrointestinal or renal fluid losses > 500 g/d or > 1000 g/d in the setting of edema Urine protein < 500 mg/dL No ultrasonographic evidence of primary renal disease No sustained improvement in renal function after hydration MINOR Urine sodium < 10 mEq/L Urine osmolality > plasma osmolality Urine red blood cells < 50 per high power field Urine output < 500 mL/d Serum sodium < 130 mEq/L For the diagnosis of hepatorenal syndrome, all major criteria must be met. Minor criteria are supportive but not necessary for the diagnosis. INTENSIVE MANAGEMENT OF HEPATIC FAI LURE/RINELLA, SANYAL 253 found that only albumin improved hemodynamics in patients with SBP, suggesting that it may also have direct effects on the vascular endothelium. 203 Lifelong secondary antibiotic prophylaxis is mandatory in the patient with a history of SBP. Oral quinolones are most commonly used (norfloxacin); however, many antibiotics are effective for secondary prophylaxis of SBP. ASCITES Ascitesistheresultofavidwaterandsodiumretention characteristic of the altered hemodynamics of cirrhosis and portal hypertension. It is associated with a 50% 2-year survival. Uncomplicated ascites is managed with sodium restriction (< 88 mmol/d) and diuretics; potassium sparing (i.e., spironolactone) alone, or in combination with a loop diuretic (i.e., furosemide). Diuretics are advanced until therapeutic efficacy is achieved or limited by worsening renal function or hyponatremia. In diuretic-refractory or resistant cases repeat large-volume paracentesis (LVP) with albumin infusion, TIPS, or peritonovenous shunts can be effective in improving the ascites but does not improve survival. 204,205 Ascites can be a difficult problem to manage in the ICU. Copious colloid and crystalloid infusion inevitably worsens ascites and diureti c use is often limited by hyponatremia, hypotension, or renal failure. Massive ascites can also alter respiratory mechanics and make breathing mo re labored or mechanical ventilation more challenging. Occasionally, massive ascites can worsen renal failure through compression of the renal arteries. LVP should be reserved for patient discomfort and improvement of respiratory mechanics when possi- ble to avoid large-volume shifting and activation of vasoactive neurohumoral systems after paracentesis that can worsen renal perfusion. Such changes can be mini- mized with the use of albumin (6 to 8 g/L removed). Albumin administration helps maintain intravascular volume and minimize postparacentesis circulatory dys- function. 205,206 RENAL FAILURE Twenty percent of cirrhotic patients with tense ascites develop renal failure characterized by the hepatorenal syndrome (HRS). 207,208 HRS is defined as functional renal impairment in a patient with advanced liver disease in the setting of normal tubular function and renal histology 209 (Table 6). Two types of HRS have been described; HRS I and HRS II, based upon the rapidity and extent of renal failure. 210 HRS I is characterized by a rapid and severe deterioration of renal function with survival measured in days to weeks, and HRS II repre- sents a more indolent and stable renal dysfunction. Table 6 illustrates the International Ascites Club classi- fication of HRS. The pathophysiology of HRS is complex. Splanchnic arteriolar vasodilation leads to central vaso- dilation and compensatory activation of systemic and renal vasoconstrictor systems. 107,211 The resultant renal vasoconstriction leads to reduced glomerular filtration rate and increased water and sodium retention. Treatment of Hepatorenal Syndrome Liver transplantation is the ultimate treatment for HRS. After transplantation renal function returns to baseline in most cases. 212,213 Combination drug ther- apy that counteracts renal and systemic vasoconstriction leading to arterial hypotension and central hypovolemia with vasoconstrictors and plasma expanders, respec- tively, is the most effective strategy. Terlipressin, a long-acting vasopressin analogue that stimulates splanchnic V 1a vasopressin receptors increases blood pressure, GFR (glomerular filtration rate), and urine volume in patients with HRS. 214,215 Unfortunately, terlipressin is not yet available in the United States. In a small study of patients with HRS I, the combina- tion of the a-agonist midodrine (7.5 mg tid), octreotide (100 g SQ tid), and albumin (25 g/day) was effective in improving renal function. 216 In a more recent study, these findings were confirmed and insertion of a TIPS in a subset of patients led to further improvement in renal function. 217 LIVER TRANSPLANTATION—CHRONIC LIVER DISEASE Allocation of organs in chronic liver disease changed on February 27, 2002. The model of end-stage liver disease (MELD) system was adopted to objectify the way in which livers were allocated in the United States. It is a survival model based on a composite of three laboratory values: serum bilirubin, serum creatinine, and INR. The model was originally used to assess short-term mortality in cirrhotic patients undergoing elective TIPS placement. 218 This model was subsequently va- lidated as an independent predictor of survival in patients with cirrhosis. 219,220 Thus priority on the liver transplant waiting list is based on the patient’s blood group and the MELD score without emphasis on waiting time. SUMMARY Management of the patient with acute or chronic hepatic failure remains a challenging problem, despite advances in intensive care. Liver failure typically has profound effects on other organ systems and the effects of therapeutic interventions on other organs must be 254 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 considered. A multidisciplinary approach is most effec- tive and urgent transfer to a transplant center is man- datory in potential transplant candidates. 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Gastroenterology 2002;122:1658–1676 260 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 [...]... 2006;27:262–273 Published by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA Tel: +1(212) 58 4-4 662 DOI 10.1 055 /s-200 6-9 455 27 ISSN 106 9-3 424 ACUTERENAL FAILUREIN THEICU/WEISBORD, PALEVSKY patients had primarily medical causes for ICU admission; however, in 25% of cases, ARF developed in the setting of trauma or during the postoperative period In contrast, in a study of 17,126... of ARF in critically ill patients has ranged from 3 to 25% In a large, multinational study published a decade ago, ARF, defined as an increase in Scr to more than 3 .5 mg/dL or the presence of oliguria, was observed in 348 of 1411 ICU patients (24.7%).6 Nearly half of these Non-pulmonary Critical Care: Managing Multisystem Critical Illness; Guest Editor, Curtis N Sessler, M.D Semin Respir Crit Care Med... (111F-U), VA Pittsburgh Healthcare System, University Drive Division, Pittsburgh, PA 152 40 E-mail: palevsky@pitt.edu 262 209 cases per million persons.1,2 Other series have demonstrated community-acquired ARF in 0.4 to 0.9% of hospital admissions,3 whereas hospital-acquired ARF developed during 4.9 to 7.2% of hospitalizations, with an apparent increase in incidence over a 2 decade interval.4 ,5 With... interval.4 ,5 With a well-recognized relationship between severity of illness and risk for ARF, it is not surprising that the incidence of ARF increases dramatically in the intensive care unit (ICU) setting Over a 10-month period spanning 1991 to 1992, Liano and Pascual studied the epidemiology of ARF in 13 tertiary -care hospitals in Madrid, Spain.2 Of the 747 episodes of ARF that were identified, 253 (34%) occurred... nephropathy (RCN). 15 After adjustment for comorbidities, there was a 5. 5-fold increased mortality risk associated with the development of ARF The increased mortality risk was greatest in patients with the lowest levels of comorbid illness, and declined as the burden of comorbid conditions increased Although this study was not restricted to critically ill patients, other studies restricted to critically ill... requiring ICU care OUTCOMES OF ACUTE RENAL FAILURE Much like efforts to describe the epidemiology of ARF, attempts to characterize outcomes associated with ARF are confounded by the different definitions that have been employed A series of studies in demographically diverse populations have demonstrated in-hospital mortality rates in critically ill patients with ARF that range from $ 35% to as high as 75% .7,9–13... characteristics of the patient population studied but also the particular criteria used to define ARF In two large European studies, the overall population-based annual incidence of ARF was 140 to 1 Renal Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania; 2Center for Health Equity Research and Promotion; 3 Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of... livers Gastroenterology 2003;124:91–96 261 Acute Renal Failure in the Intensive Care Unit Steven D Weisbord, M.D., M.Sc.1,2,3 and Paul M Palevsky, M.D.1,3 ABSTRACT Acute renal failure (ARF) is a common complication in critically ill patients, with ARF requiring renal replacement therapy (RRT) developing in $ 5 to 10% of intensive care unit (ICU) patients Epidemiological studies have demonstrated that ARF... hepatorenal syndrome Hepatology 2004;40 :55 –64 218 Malinchoc M, Kamath PS, Gordon FD, Peine CJ, Rank J, ter Borg PC A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts Hepatology 2000;31:864–871 219 Wiesner RH, McDiarmid SV, Kamath PS, et al MELD and PELD: application of survival models to liver allocation Liver Transpl 2001;7 :56 7 58 0 220 Wiesner R, Edwards E,... mortality in multiple other studies of ARF in critically ill patients Metnitz and colleagues found a fourfold higher mortality rate among patients requiring RRT for ARF than in patients without ARF (62.8% vs 15. 6%; p < 001).7 This excess mortality persisted after adjustments for illness severity, age, and treatment center Similarly, in the Program to Improve Care in Acute Renal Disease (PICARD), a multicenter . Rm.7E123 (111F-U),VA Pittsburgh Healthcare System, Univer- sity Drive Division, Pittsburgh, PA 152 40. E-mail: palevsky@pitt.edu. Non-pulmonary Critical Care: Managing Multisystem Critical Illness; Guest. Respir Crit Care Med 2006;27:262–273. Published by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 58 4-4 662. DOI 10.1 055 /s-200 6-9 455 27. ISSN 106 9-3 424. 262 patients. Surgery 2001;130: 354 –362 75. Rose C, Michalak A, Rao KV, Quack G, Kircheis G, Butterworth RF. L-ornithine-L-aspartate lowers plasma and 256 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME