Non-pulmonary Critical Care - part 4 ppt

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Fluid-management strategies in acute lung injury—liberal, conservative, or both? N Engl J Med, June 2006;10.1056/NEJM e068105. Available at www.nejm.org 98. Bernard GR, Vincent JL, Laterre PF, et al. Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study group: efficacy and safety of recombi- nant human activated protein C for severe sepsis. N Engl J Med 2001;344:699–709 99. van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med 2001;345:1359–1367 100. Liang DH, Thompson N. A program for the use of hand- held echocardiography by intensivists to augment physical exam assessment. 33rd Critical Care Medicine Congress. Orlando Feb 2004. Crit Care Med 2003:33(Suppl)– A21 101. Vignon P, Frank MBJ, Lesage J, et al. Handheld echocardio- graphy with Doppler capability for the assessment of critically ill patients: is it reliable? Intensive Care Med 2004;30:718– 723 102. Monnet X, Rienzo M, Osman D, et al. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med 2006;34:1402–1407 240 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 Intensive Management of Hepatic Failure Mary E. Rinella, M.D. 1 and Arun Sanyal, M.D. 2 ABSTRACT A substantial number of patients with liver failure are admitted to the intensive care unit; thus a thorough understanding of the prevention and treatment of complications in such patients is imperative. The management of liver failure is demanding and often involves the combined efforts of many specialists. Critically ill patients with hepatic failure encompass a broad spectrum of disease, ranging from acute liver failure in a patient with no prior history of liver disease, to acute on chronic liver failure. The initial assessment and management of acute liver failure are reviewed with an emphasis on the prevention and treatment of brain edema in the pretransplant setting. The current treatment of compli- cations resulting from decompensated chronic liver disease such as portal hypertensive bleeding; infection, renal failure, and hepatic encephalopathy are then discussed. KEYWORDS: Liver failure, cerebral edema, portal hypertension, management The management of liver failure is demanding and often involves the combined efforts of many special- ists. Critically ill patients with hepatic failure encompass a broad spectrum of disease, ranging from acute liver failure in a patient with no prior history of liver disease, to end-stage decompensated cirrhosis. Both sides of this spectrum presen t clinical challenges that involve many organ systems. Although both sides in acute and chronic liver failure can have a poor prognosis, careful and comprehensive intensive care can improve outcome and bridge eligible patients to liver transplantation. Because acute and chronic liver failure are very distinct clinical entities, they will be discussed separately. ACUTE LIVER FAILURE Acute liver failure (ALF) is a rapidly progressive, often fatal syndrome characterized by jaundice, encephalop- athy, and coagulopathy leading to multiorgan failure in a patient with no prior history of liver disease. 1,2 In recent years, advancements in supportive care have improved survival and provided a more effective bridge to trans- plantation. Although ALF remains one of the most acute serious illnesses, thoughtful intensive management can optimize the patient’s chances for spontaneous hepatic regeneration or a successful liver transplant. 3 When possible, etiology-targeted therapy should be initiated (Table 1). The goal of management should be focused on the prevention of systemic infection, multiorgan fail- ure, hepatic encephalopathy (HE), and ultimately the development of brain edema. 4–6 At this time liver trans- plantation is the only definitive therapy for those who fulfill criteria for poor prognosis 7–9 (Table 2). The challenge to the clinician is selection of patients for transplant that have low likelihood of spontaneous sur- vival but are not too ill to benefit from transplantation. The principles of management of ALF are reviewed here: INITIAL EVALUATION AND MANAGEMENT Early diagnosis and identification of the subject that is unlikely to improve spontaneously constitute a critical first step in the management of ALF. The initial triage 1 Division of Hepatology, Northwestern University, Chicago, Illinois; 2 Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia. Address for correspondence and reprint request s: Arun Sanyal, M.D., Division of Gastroenterology, Department of Internal Med- icine, Virginia Commonwealth University, MCV Box 980341, Richmond, VA 23298-0341. E-mail: ajsanyal@hsc.vcu.edu. Non-pulmonary Critical Care: Managing Multisystem Critical Ill- ness;GuestEditor,CurtisN.Sessler,M.D. Semin Respir Crit Care Med 2006;27:241–261. Copyright # 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel: +1(212) 584-4662. DOI 1 0.1055/s-2006-945528. ISSN 1069-3424. 241 of a patient with acute liver injury to an intensive care unit (ICU) is based on the presence of altered mental status and the degree of coagulopathy. It is imperative toadmitmostsubjectswithacuteliverinjurywithan international normalized ratio (INR) > 1.5 and all subjects with mental status changes. Rapid deteriora- tion can occur and is often irreversible in the patient with ALF. It is therefore imperative that decisions regarding prognosis and appropriateness for liver trans- plant be made early, and potentially suitable patients should be referred to a liver transplant center early in the evaluation process. The management of patients in liver failure requires a multidisciplinary approach involving hepatol- ogists, transplant surgeons, intensivists, and other sub- specialists. The importance of a thorough physical exam and an accurate history cannot be overemphasized be- cause both treatment and prognosis are significantly affected by the underlying etiology. A detailed account of the psychiatric history, including suicidal ideation and family support, is essential to assess suitability for transplantation. The timing of the psychiatric evalua- tion is of particular importance, given the rapid deterio- ration in mental status that occurs in such patients. DISEASE-TARGETED THERAPY A thorough discussion of the differential diagnosis of ALF is beyond the scope of this review; however, Table 1 provides a summ ary of common etiologies of ALF for which potential therapies exist. Only acetami- nophen will be discussed in more detail because it is the most common etiology of liver failure in the United States and has an effective antidote. Acetaminophen Idiopathic and drug-related liver injuries are the most common causes of ALF in the United States. 10 Of the drug-related causes, acetaminophen overdose is the most common cause of ALF in the United Kingdom and United States. Overdose can be either intentional or unintentional. 11–13 The patient, family, and close contacts must be questioned about regular alcohol use, dieting, diet pills, medications, or recent illness that may have resulted in poor nutrition. These factors greatly affect toxicity either through upregulating cytochrome p450 (alcohol and other drugs) promoting the formation of toxic inter- mediates, or through glutathione depletion. Such details are important because as little as 2.6 to 4.0 g of acetami- nophen can lead to liver failure in this setting. 14–17 It is worth noting that, at the time of presenta- tion, a patient with acetaminophen-induced liver failure may have undetectable blood levels of acetaminophen. This is pa rticularly true when the toxicity manifests itself several days after ingestion of acetaminophen for ther- apeutic purposes in a susceptible subject. However, in the majority of cases, detectable acetaminophen levels are present at the time of presentation. When acetami- nophen overdose is confirmed, N-acetylcysteine (NAC) must be initiated in a timely manner, ideally within 16 hours of ingestion, to have a significant impact on survival. NAC decreases injury through enhancement of glutathione synthesis resulting in less formation of acetaminophen’s hepatotoxic intermediate. 18,19 Even if the patient is delayed in reaching the hospital or the diagnosis is not forthcoming, there is evidence that late administration of NAC can be beneficial. 20 NAC may also improve outcome through its effects on micro- circulatory function. A large multicenter study (the ALF study group) is currently addressing the utility of NAC in nonacetaminophen-induced ALF. Table 1 Etiology-Targeted Therapy Etiology Potential Therapies TOXIC Acetaminophen N-acetyl cysteine Amanita poisoning Penicillin and silibinin VIRAL Herpes simplex virus Acyclovir Acute heptatitis B Antivirals? METABOLIC Wilson’s disease Transplant Autoimmune hepatitis Corticosteroids VASCULAR Acute Budd-Chiari syndrome Directed thrombolysis, transjugular intrahepatic portosystemic shunt PREGNANCY Acute fatty liver of pregnancy/HELLP Urgent delivery HELLP, hemolysis elevated liver enzymes low platelets. Table 2 King’s College Criteria for Acute Liver Failure Acetaminophen induced  Arterial blood pH < 7.3 (regardless of degree of encephalopathy) If no acidosis then all three of the below criteria:  Prothrombin time > 100 seconds  Serum Creatinine > 2.5 mg/dL  Grade 3 or 4 encephalopathy Nonacetaminophen induced  Prothrombin time > 100 seconds If prothrombin time < 100 seconds, then any of the below criteria (regardless of degree of encephalopathy):  Drug-induced, non-A, non-B, halothane hepatitis  Time from jaundice to encephalopathy > 7 days  Age < 10 or > 40 years  Prothrombin > 50 seconds  Bilirubin > 17.5 mg/dL 242 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 MONITORING AND GENERAL GUIDELINES Acute hepatic dysfunction has profound effects on many organs. Therefore, one must remain cognizant of the ramifications of specific therapies on other systems. The mental status must be documented several times daily, in addition to frequent assessment of hepatic synthetic function and blood glucose (Table 3). Although a liver biopsy may be helpful if the diagnosis is in question, it can be unreliable in predicting outcome and is risky given the presence of underlying coagulopathy. 21 Low serum phos- phate and elevated a fetoprotein can be encouraging signs of hepatic regeneration. 22,23 In a retrospective analysis of ALF patients, 74% of patients with phosphate levels < 2.5 were alive at 1 week, in contrast to none in those with a serum phosphate > 5. 24 Coagulopathy in ALF does not usually require correction unless an invasive procedure is planned or overt bleeding is present because the use of fresh frozen plasma (FFP) can mask deterioration of liver function. A common indication for the correction of coagulopathy is placement of a central line. Traditionally, FFP and cryoprecipitates have been used for the correction of coagulopathy in subjects with ALF. This is only partially effective in correcting coagulopathy and its effects are short-lived. It is also associated with a risk of transmitting cytomegalovirus infection and may contribute to volume overload and pulmonary edema, especially when renal function begins to deteriorate. Alternate approaches in- clude the use of plasmapheresis where a volume of plasma equal to the amount infused is removed to prevent volume overload. Recently, recombinant factor VII (40 mg/kg) has been used in conjunction with FFP to rapidly correct coagulopathy prior to either intracranial pressure monitor or central line placement in patients with ALF. 25 MECHANICAL VENTILATION Mechanical ventilation should be initiated once ence- phalopathy deteriorates to ! grade 3 (West Haven cri- teria) to protect the airway. 26,27 In addition to preventing aspiration in the patient with compromised mental status, intubation and sedatives help control agitation, which can lead to surges in intracranial pressure. Patients with encephalopathy beyond grade 3 are very difficult to manage without intubation and sedation. 28 Sedation is best achieved with a short-acting sedative alone or in combination with a short-acting narcotic. Recent evidence supports the use of propofol for this purpose. In a small study, propofol was given to seven patients with ALF and profound encephalopathy. Intracranial pressure (ICP) remained normal in six of Table 3 Acute Liver Failure: General Management Guidelines On Admission Daily Tid Hourly If Indicated Monitoring IV access, CVP and arterial line, Foley catheter Blood sugar Mental status Mechanical intubation, ICP monitoring Thorough history and physical Interview family members Laboratories Liver panel, renal panel, CBC, PT, Hep A,B,C serologies, HSV, CMV, EBV, ceruloplasmin, ANA, anti-sm Ab, SPEP, HIV, acetaminophen level, toxicology screen, cosyntropin stimulation test, TSH, blood type, blood cultures Basic laboratories, AFP, arterial ammonia (or more if mental status deteriorating phosphate, factor V level Blood gas Changes in ICP monitor Imaging US with Doppler Head CT for neurological changes or suspected edema Directed therapy where indicated Drugs, cooling for cerebral edema AFP, alpha feta protein; ANA, antinuclear antibody; anti-sm Ab, antismooth muscle antibody; CBC, complete blood count; CMV, cytomegalo- virus; CT, computed tomography; CVP, central venous pressure; EBV, Epstein-Barr virus; HSV, herpes simplex virus; HIV, human immunode- ficiency virus; ICP, intracranial pressure; IV, intravenous; PT, prothrombin time; SPEP, serum protein electrophoresis; TSH, thyroid stimulating hormone; US, ultrasound. INTENSIVE MANAGEMENT OF HEP ATIC F AILURE/RINELLA, SANYAL 243 seven patients with ALF given propofol at 50 mg/kg/ min, suggesting propofol may have independent benefi- cial effects on ICP. 29 Paralytics are usually avoided because they can mask seizure activity. However, they may be used in specific cases to facilitate management when the subject does not respond appropriately to sedation. In such cases, it is imperative to consider the possibility of seizure activity if the clinical picture continues to deteriorate. H2 antagonists or proton pump inhibitors may decrease the incidence of ulcer disease in mechanically ventilated patients 30 ; however, the theoretical risk of increasing the incidence of pneumonia has not been studied in this population. PREVENTION AND MANAGEMENT OF COMPLICATIONS Circulatory Dysfunction Derangements in circulatory function manifest early in ALF and are often progressive. They are characterized by generalized vasodilation, increased cardiac output, de- creased systemic vascular resistance, and a low mean arterial pressure (MAP). 31–33 It is challenging to distin- guish this clinical picture from the hemodynamics of sepsis, particularly given that infection is common and often a fatal complication. 34 Factors such as adrenal insufficiency also complicate management by making the vasculature less responsive to vasopressive agents. 35,36 In general terms, fluids and vasopressors should be used to maintain adequate cerebral perfusion pressure (CPP) (50 mm Hg to 65 mm Hg) while avoiding cerebral hyperemia from hyperperfusion. 37,38 Because the circulatory disturbance in ALF is characterized by vasodilation and increased car diac output, norepinephr- ine is frequently the vasopressor of choice. Infection Patients with ALF are particularly susceptible to severe infection due to many immunological defects such as defective phagocytic function and decreased comple- ment levels. 39–42 Bacterial or fungal sepsis is a frequent cause of death in this population. Much like other immunocompromised hosts, their response to infection is atypical in that signs such as fever or leukocytosis are absent in 30% of cases. 43 Thus sepsis is both frequent and difficult to diagnose in subjects with ALF. In a prospective study of 887 patients with ALF, one or more bacterial infections occurred in 37.8%; however, an incidence of up to 80% has been reported. 44 Of these, gram-positive cocci were the most common organisms isolated, although Escherichia coli and Klebsiella were also frequent pathogens. 45 Overall, pneumonias make up 50% of bacterial infections in ALF with bacteremia and urinary tract infections occurring in 20 and 25%, respectively. These infections presented at a median of 5, 3, and 2 days after the onset of A LF. 44 Given the frequency of both gram-negative and gram-positive infections in this population, broad spec- trum antibiotic coverage should be administered avoid- ing aminoglycosides due to their nephrotoxicity. 34 Although no randomized controlled trials have demon- strated improved survival with prophylactic antibiotics, parenteral antibiotics are associated with a lower inci- dence of infection 46 (Fig. 1). 47 Given these data, pro- phylactic broad-spec trum antibiotics seem justifiable given that uncontrolled infection in such patients is often catastrophic. 48,49 Systemic Inflammatory Response Syndrome Even in the absenc e of documented infection, systemic inflammatory response syndrome (SIRS) is common in those with ALF and is likely due to a surge of cytokine release. 50 In a study from King’s College, 57% of 887 patients with ALF developed SIRS. The presence of SIRS on admission was independently associated with more severe illness, worsening of encephalopathy, and subsequent death. In those patients that were infected (54%), mortality increased with each additional compo- nent of SIRS. At this point it remains unclear how additional infection contributes or which component of the observed inflammatory response originates from humoral factors released by the necrotic liver. 34,46,51 Adrenocortical Insufficiency Adrenocortical insufficiency can worsen hyperdynamic cardiovascular collapse typical of ALF or septic shock. 52 This should be considered when the patient fails Figure 1 The effect of antibiotic prophylaxis on the prevalence of documented infection patients with acute liver failure. (Adapted from Salmeron et al. 47 ) 244 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 to respond to volume resuscitation. 35 In sepsis, supra- physiological doses of steroids in patients with adrenal insufficiency have been shown to reduce vasopressor requirements and improve outcome. 36,53 Adrenal dysfunction appears to also be prevalent in patients with ALF; 62% of patients with ALF were found to have an abnormal response to high-dose corticotrophin stimulation. The patients with pronounced hemody- namic instability had more marked evidence of adrenal insufficiency, suggesting that it may contribute to the pattern of cardiovascular collapse seen in liver failure. 54 The benefit of stress-dose steroids in this population needs to be tested in a randomized-controlled trial; however, given these data, it is reasonable to look for and consider treating adrenal insufficiency in patients with ALF. Renal Failure Renal failure is common in those with advanced liver failure and is multifactorial in etiology. Common causes of renal failure in this population include prerenal azotemia, renal ischemia, acute tubular necrosis, and hepatorenal syndrome. A majority of patients with ALF complicated by profound hypotension and cerebral edema will require renal replacement therapy. 31 Due to the marked vasodilation that characterizes such patients, continuous venovenous hemofiltration (CVVH) tends to be better tolerated and may have more beneficial effects on ICP. 55,56 Moreover, intermittent hemodialysis has been associated with increases in ICP and decreases in CPP, whereas the opposite has been shown in patien t s receiving CVVH. 55,57 Hepatic Encephalopathy and the Development of Intracranial Hypertension The development of HE and subsequent cerebral edema and intracranial hypertension (ICH) define prognosis in patients with ALF. 2,7,58 Treatment options for such patients are limited. As a result, $30% of patients with ALF and cerebral edema succumb to cerebral herniation while awaiting an organ. 7,31 Without urgent transplantation, mortality can exceed 90% in those who have uncontrolled ICH. The pathogenesis of cerebral edema is complex (Fig. 2). ALF leads to many hemodynamic changes, including impairment of cerebrovascular autoregulation and blood flow. This impairment makes the standard assumption that CPP ¼ MAP À ICP less reliable. 38 Other factors such as high arterial ammonia levels contribute to brain edema through the accumulation of glutamine and alanine in astrocytes. In response to swelling, a vasodilating factor is released that leads to increased CBF and thus increased ICP. 59 Arterial ammonia levels > 200 mmol/L in the setting of ALF have been shown to herald impending cerebral herniation and poor outcome. 60,61 Other Figure 2 Factors leading to the development of brain edema and potential therapeutic interventions. INTENSIVE MANAGEMENT OF HEP ATIC F AILURE/RINELLA, SANYAL 245 markers of brain cell dysfunction and damage such as s100-b and neuron-specific enolase (NSE) have also been evaluated as potential predictors of impending herniation in the setting of ALF and acute on chronic liver failure with negative results. 62 Currently, no serum markers of brain cell dysfunction reli ably demonstrate neurological injury and poor outcome. Unfortunately, it can be difficult to predict which patients are likely to develop elevated ICP. Clinical signs such as arterial hypertension, fever, and agitation can precede episodes of severe ICH; however, these are not reliable predictors because elevated ICP is often clin- ically silent. 63 Although a computed tomographic (CT) scan is usually used to look for cerebral edema, a normal scan does not exclude the presence of edema because its appearance on imaging may be delayed. INTRACRANIAL PRESSURE MONITORING A significant clinical challenge in the management of ALFisthedecisiontoplaceanICPmonitor.Thereare no strict guidelines related to the use of these monitors andexperienceacrossinstitutionsishighlyvariable. Noninvasive techniques have not proven to be benefi- cial and direct ICP monitoring is the only reliable modality for the measurement of ICP. The benefit that can be derived from ICP monitoring is twofold. First, it allows for the early detection and treatment of ICH because it can be clinically silent. 63 Second, it can provide invaluable information about the likelihood of neurological recovery when deciding whether to pro- ceed with liver transplantation, such as when CPP is persistently low. Sustained CPP < 40 mm Hg predicts a high likelihood of ischemic brain injury th at typically results in a poor neurological outcome after transplan- tation. 64,65 Figure 3 proposes an algorithm for the use of ICP monitor s in A LF. Although treatments aimed at reducing ICP can be used without an ICP monitor, an accurate ICP reading permits targeted therapy to optimize CPP and detect abrupt surges in pressure that necessitate addi- tional therapy. Concomitant measurement of jugular bulb oxygen saturation, 32,66 which allows measurement of brain oxygen utilization, can also be useful in the management of these patients. 32 Jugular bulb oxygen saturation > 80% or < 60% predicts elevation in ICP with good sensitivity and specificity. 31 Jugulovenous O 2 saturations < 50% may herald an increase in anaerobic cerebral glycolysis, increased lactate:pyruvate ratio, and worsening cerebral edema. 67 When and in Whom to Insert an Intr acranial Pressure Monitor To justify the risks of ICP monitor placement, the monitor needs to be placed under controlled circum- stances, when increased ICP is likely to rise but before uncontrolled ICH and herniation occur. ICP monitor- ing should be considered for mechanically ventilated patients with grade 3 or 4 encephalopathy with poor prognosis (Table 2) but who are otherwise good candi- dates for liver transplant (Fig. 3). Other predictors of increased ICP such as arterial ammonia > 150 mmol/L could be used to time monitor placement. In those with poor prognosis without orthopedic liver transplant (OLT), ICP monitoring can guide therapy and prevent surges in ICH before and during OLT. Risks of Intracranial Pressure Monitoring As with all interventions, the risks of ICP monitor placement need to be balanced against the accuracy and usefulness of the information to be gained. No random- ized, controlled trial is available to compare different Figure 3 Proposed algorithm for the use of an intracranial pressure monitor. 246 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 catheters in the setting of ALF. Types of catheters include epidural, subdural, parenchymal, and intraventricular catheters. Blei et al performed a survey of transplant centers across the United States. They estimated that 20% of ICP monitoring resulted in intracranial bleeding. Epidural catheters had the lowest rate of bleeding com- plications (3.8%) and subdural and parenchymal catheters the highest; 20% and 22%, respectively. 68 A recent multi- center study from the ALF study group showed that ICP monitors were only used in 92/332 patients (28%) with ALF and severe encephalopathy; however, the frequency of monitoring differed between centers. Ten percent had intracranial bleeding as a result of the ICP monitor. In two of these patients, ICP monitoring was directly associated with the patient’s death. 69 Although the risk of complications is greater, 70 subdural catheters give a more reliable estimate of ICP than epidural catheters. 68 Bleeding complications can be decreased signifi- cantly with the use of recombinant factor rVIIa given immediately before the procedure. 25 The frequency of factor VII dosing was variable in this study; however, as a group all patients that received factor VII normalized their prothrombin time (PT) and were able to have ICP monitors placed (compared with 38% in the FFP alone group). The ideal initial dose and subsequent doses of factor VII necessitates further study. 71 The data show that ICP monitoring can be an effective tool for manag- ing elevated intracranial pressure; however, ICP mon- itors have not been shown to improve survival. Currently there is no consensus about the use of ICP monitoring or whether the more accurate but higher-risk subdural catheters or the less accurate but safer epidural catheter should be used. Individual centers will continue to use what they are comfortable with; however, their decision may be influenced by the decreased availability of epi- dural catheters. Prevention and Treatment of Increased Intracranial Pressure Routine measures such as elevation of the head of the bed to 30 degrees, 55 sedation, minimal stimulation, and mechanical ventilation to minimize cerebral stimulation should be adhered to whenever possible. The manage- ment should be focused on maintaining an adequate CPP (> 50 mm Hg) while minimizing elevations in ICP (< 20 mm Hg). Blood pressure should be maintained to achieve a CPP between 50 and 65 mm Hg. Prolonged CPP below 50 mm Hg in the setting of ICH or an ICP greater than 40 mm Hg is associated with poor out- come. 65 HYPERTONIC SALINE The use of hypertonic saline is thought to help restore the osmotic gradient across the astrocyte membrane. A randomized, controlled trial recentl y demonstrated that induction and maintenance of hypernatremia (145 to 155 mmol/L) in patients with grade 3 or 4 encephalop- athy resulted in a decreased incidence and severity of ICH. 72 Other techniques to reduce brain water accu- mulation through the reduction of arterial ammonia remain under investigation. 73–75 MANNITOL Mannitol administration leads to increased plasma os- molality in brain capillaries, resulting in movement of water out of the brain according to Starling’s law. It has been shown to decrease episodes of cerebral edema and result in improved survival in a cohort of patients with ALF (47.1 and 5.9%, respectively, p ¼ .008). 76 Its use, however, is limited in renal failure and can lead to a paradoxical increase in brain swelling if osmolality is not controlled. If more than two doses are to be used, plasma osmolality must be checked to assure that it remains < 320 Osm/L. HYPERVENTILATION Hyperventilation is an effective technique to decreas e cerebral blood flow (CBF) and ICP. It does so through precapillary hypocapnic vasoconstriction and helps re- store CBF autoregulation. 61,77–79 Although prophylactic hyperventilation appears to be ineffective in preventing the development of ICH, 77 it can be useful in controlling acute surges in ICP. INDOMETHACIN Indomethacin leads to cerebral vasoconstriction effects via altering cerebral temperature and extracellular pH and inhibition of the endothelial cyclooxygenase path- way. 80 Its effectiveness has been proven in an animal model 81 and in a small cohort of patients with ALF. 82 However, due to its multiple systemic side effects in patients with ALF, its routine use cannot be supported. THIOPENTAL SODIUM In a small, uncontrolled study, thiopental sodium was effective in reducing ICP. 83 Unfortunately, its use is associated with significant hemodynamic derangements that may necessitate escalation of vasopressor or inotropic support. Thus thiopental use should be reserved for surges of ICH unresponsive to standard medical therapy. HYPOTHERMIA Moderate hypothermia (32 to 33  C) in animal models of ALF has been effective in improving encephalopathy and reducing brain water. 84,85 Clinical studies of hypo- thermia have also shown significant reduction in ICP. Jalan et al were able to demonstrate that cooling patients with refractory ICH to 32  C decreased ICP to < 20 mm Hg. Subsequently they demonstrated a reciprocal in- crease in ICP with rewarming. 86 Since this study, the same and other groups have also shown that moderate INTENSIVE MANAGEMENT OF HEP ATIC F AILURE/RINELLA, SANYAL 247 [...]... retrospective analysis reported in-hospital, 6-week, and overall mortality rates of 14. 2%, 17.5%, and 33.5%, respectively, suggesting improved therapy of AVH has impacted survival.118 Oneyear survival following a variceal bleed greatly depends on the severity of liver disease assessed by the Child-Pugh classification (Table 4) Mortality after a variceal hemorrhage is 5% and 50% in Child-Pugh A and C cirrhotic... special detachable endoscopically placed snares. 140 , 141 Although there is limited experience with the technique in the United States, the Japanese report success with balloonoccluded retrograde transvenous obliteration (B-RTO) of isolated gastric varices. 142 , 143 Unfortunately, most of these modalities are not routinely available in the United States The first-line approach to the control of actively bleeding... are present in up to 57% of patients with esophageal varices secondary to portal hypertension.127 Less commonly, they are found in the absence of esophageal 249 250 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 2006 Figure 4 Proposed algorithm for the management of acute variceal bleeding varices.128 If isolated gastric varices are noted imaging must be performed to exclude splenic... the portal vein with a TIPS as the definitive procedure of choice in most patients before discharge from the hospital. 144 , 145 It is often necessary to embolize prominent portosystemic collaterals at the time of TIPS to reduce the risk of bleeding When this is not done, nonselective b-blockers may be used to reduce the ... 248 SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE/VOLUME 27, NUMBER 3 hypothermia is effective in the prevention of ICH in ALF, as a bridge to transplant,87 and during liver transplantation88 to prevent surges in ICP... approach that will bridge eligible patients to transplantation and improve short-term survival in nontransplant candidates PORTAL HYPERTENSIVE BLEEDING Portal hypertensive hemorrhage is a serious and frequent complication of advanced cirrhosis.107–109 Bleeding can INTENSIVE MANAGEMENT OF HEPATIC FAILURE/RINELLA, SANYAL Table 4 Child-Pugh Score Score Bilirubin/mmol/L Albumin/g/L INR Ascites Encephalopathy... Bilirubin/mmol/L Albumin/g/L INR Ascites Encephalopathy 1 3.5 < 1.3 Absent 0 2 2.1–3 2.8–3.5 1.3–1.5 Mild I/II 3 >3 < 2.7 > 1.5 > Moderate III/IV The Child-Pugh score is derived from the sum of the assigned points in each category Child-Pugh A, B, and C are defined as < 6, 7–9, and > 10, respectively INR, international normalized ratio originate from gastroesophageal varices, portal hypertensive... randomized controlled trial, ELAD resulted in less severity of encephalopathy without improvement in survival. 94 Overall, the data on bioartificial liver devices are disappointing in that they are quite costly and have not resulted in improved synthetic function or survival.95 MARS removes free and albumin-bound toxins via a polysulfone membrane.96,97 In contrast to bioartificial devices, MARS has mainly been... therapy.1 14 The management of patients with gastroesophageal varices involves (1) prevention of the initial bleed (primary prophylaxis is beyond the scope of this review), (2) management of the acute bleed, and (3) prevention of rebleeding (secondary prophylaxis) Variceal Hemorrhage—General Considerations Acute hemorrhage typically presents with hematemesis with or without melena or hematochezia Hemody- namic... airway protection Figure 4 proposes an algorithm for the management of AVH Esophageal Variceal Hemorrhage Mortality associated with AVH has improved in the past decade.123 Based on data comparing patients presenting with AVH from 1981–82 to 1988–91, the late cohort experienced a significant decline in mortality at 30 days (20.8% vs 29.6%, p ¼ 0001) and at 6 years (69.7% vs 74. 5%, p ¼ 0001) For patients . Department of Internal Med- icine, Virginia Commonwealth University, MCV Box 980 341 , Richmond, VA 2329 8-0 341 . E-mail: ajsanyal@hsc.vcu.edu. Non-pulmonary Critical Care: Managing Multisystem Critical. Avenue, New York, NY 10001, USA. Tel: +1(212) 58 4- 4 662. DOI 1 0.1055/s-200 6-9 45 528. ISSN 106 9-3 42 4. 241 of a patient with acute liver injury to an intensive care unit (ICU) is based on the presence. Intensive Care Med 20 04; 30:718– 723 102. Monnet X, Rienzo M, Osman D, et al. Passive leg raising predicts fluid responsiveness in the critically ill. Crit Care Med 2006; 34: 140 2– 140 7 240 SEMINARS