Outcome of orthotopic liver transplantation in the aetiological and clinical variants of acute liver failure

Thirty-three patients with acute liver failure underwent orthotopic liver transplantation, including 16 with fulminant hepatic failure, 15 with late-onset hepatic failure and two with severe acute liver failure (coagulopathy without encephalopathy). Twenty-three (70 per cent) survived to leave hospital and 21 of these are currently alive and well. Outcome correlated with the serum bilirubin level before transplantation (p less than 0.05) but no correlation was found with the variant of acute liver failure, grade of encephalopathy, cerebral oedema, serum creatinine, white cell count, prothrombin time or platelet count at the time of transplantation. Severe coagulation factor deficiencies did not constitute a clinical problem. One patient developed a neurological deficit secondary to cerebral oedema, but otherwise the morbidity reflected that observed in the general population after transplantation. Careful monitoring of intracranial pressure and surveillance (with early aggressive therapy) for bacterial and fungal infections is very important in achieving a successful outcome after transplantation.     

Emergency cranial computed tomography in the management of acute febrile encephalopathy in children.

OBJECTIVE: Evaluation of the influence of emergency cranial computed tomography on the management of acute febrile encephalopathy in children. METHODS: A retrospective study in children with acute febrile encephalopathy who underwent emergency cranial computed tomography within 12 hours of admission to the paediatric intensive care unit. All scans were evaluated by two independent radiologists. RESULTS: Thirty nine children were included. Fourteen scans were abnormal and two had clinically insignificant incidental findings. Four children with focal neurological signs had scans demonstrating extra-axial collections. None required neurosurgical intervention. Clinically, raised intracranial pressure was present in 10 patients. Only five had cerebral oedema on computed tomography; these five children died. Emergency cranial computed tomography influenced subsequent management in no child without focal neurological signs and in only one child with focal neurology. CONCLUSION: Emergency cranial computed tomography in acute febrile encephalopathy in children without focal neurological signs has little influence on subsequent management. Where cranial computed tomography is thought to be necessary, it should be carried out when the child's clinical condition has been stabilised.     

Assessment and management of cerebral edema and intracranial hypertension in acute liver failure

Acute liver failure is uncommon but not a rare complication of liver injury. It can happen after ingestion of acetaminophen and exposure to toxins and hepatitis viruses. The defining clinical symptoms are coagulopathy and encephalopathy occurring within days or weeks of the primary insult in patients without preexisting liver injury. Acute liver failure is often complicated by multiorgan failure and sepsis. The most life-threatening complications are sepsis, multiorgan failure, and brain edema. The clinical signs of increased intracranial pressure (ICP) are nonspecific except for neurologic deficits in impending brain stem herniation. Computed tomography of the brain is not sensitive enough in gauging intracranial hypertension or ruling out brain edema. Intracranial pressure monitoring, transcranial Doppler, and jugular venous oximetry provide valuable information for monitoring ICP and guiding therapeutic measures in patients with encephalopathy grade III or IV. Osmotic therapy using hypertonic saline and mannitol, therapeutic hypothermia, and propofol sedation are shown to improve ICPs and stabilize the patient for liver transplantation. In this article, diagnosis and management of hepatic encephalopathy and cerebral edema in patients with acute liver failure are reviewed.     

Hypothermia for the management of intracranial hypertension in acute liver failure

Increased intracranial pressure in patients with acute liver failure remains a major cause of mortality. Treatment options are limited, and without urgent liver transplantation, mortality rates of up to 90% are common in those who fulfill criteria for poor prognosis. Several studies in animal models of acute liver failure set the stage for the clinical application of moderate hypothermia in humans. Few patients are treated with hypothermia for increased intracranial pressure. However, data indicate that moderate hypothermia is a safe and effective method of treatment for increased intracranial pressure that is unresponsive to other medical therapies, and that this treatment can be used as a successful bridge to liver transplantation. Recent data also suggest that increases in intracranial pressure can be prevented during the dissection and reperfusion phases of liver transplantation for acute liver failure if patients are kept hypothermic during the surgical procedure. This article focuses on the use of moderate hypothermia for the treatment of increased intracranial pressure in patients with acute liver failure.     

Clinical management of acute hepatic failure

Acute hepatic failure is a rare clinical syndrome associated with high mortality. Hepatic failure leads to a well-recognised pattern of clinical signs and symptoms, sometimes with rapid deterioration and progression to multi-organ failure. Early recognition of this syndrome is essential for appropriate treatment; once identified, patients benefit from early interventional support and treatment in the intensive care unit. Aggressive management may allow stabilisation of patients before their transfer to specialist liver units. At present, orthotopic liver transplantation is the only treatment modality that provides significant improvement in outcome. This review examines the aetiology and clinical presentation of acute hepatic failure, providing guidelines regarding patient management. We present a critical appraisal of specific clinical areas, including the management of cardiovascular, cerebral, renal, coagulopathic and infective complications. Liver transplantation is discussed as well as emerging therapies including non-biological and hybrid liver support systems that may provide a "bridge to transplantation".     

Acute hepatic failure: the emerging role of orthotopic liver transplantation

From 1985 through 1987, we diagnosed acute hepatic failure in 13 patients. Spontaneous recovery occurred in three of these patients. Eight patients underwent liver transplantation, five of whom survived and three of whom died. In addition, two patients died before undergoing transplantation. The survival rate of 62% was better than that among our previous series of similar patients. This improvement seems to be related to the use of orthotopic liver transplantation as a therapeutic alternative among these patients. One of the three patients who died after liver transplantation had normal liver function, but respiratory failure caused by Pneumocystis carinii developed 4 months after the transplantation. The surgical procedure was less difficult in patients with acute fulminant hepatitis than in those with chronic liver disease because fewer problems arose from adhesions, venous collaterals, and ascites. The emerging role of orthotopic liver transplantation in patients with acute hepatic failure is demonstrated by the improvement of survival rates observed by various groups, including ours, when this therapeutic modality is available.     

Barriers and facilitators to provide effective pre-hospital trauma care for road traffic injury victims in Iran: a grounded theory approach

Background

It is thought that a good survival rate of patients with acute liver failure can be achieved by establishing an artificial liver support system that reliably compensates liver function until the liver regenerates or a patient undergoes transplantation. We introduced a new artificial liver support system, on-line hemodiafiltration, in patients with acute liver failure.

Methods

This case series study was conducted from May 2001 to October 2008 at the medical intensive care unit of a tertiary care academic medical center. Seventeen consecutive patients who admitted to our hospital presenting with acute liver failure were treated with artificial liver support including daily on-line hemodiafiltration and plasma exchange.

Results

After 4.9 ± 0.7 (mean ± SD) on-line hemodiafiltration sessions, 16 of 17 (94.1%) patients completely recovered from hepatic encephalopathy and maintained consciousness for 16.4 ± 3.4 (7-55) days until discontinuation of artificial liver support (a total of 14.4 ± 2.6 [6-47] on-line hemodiafiltration sessions). Significant correlation was observed between the degree of encephalopathy and number of sessions of on-line HDF required for recovery of consciousness. Of the 16 patients who recovered consciousness, 7 fully recovered and returned to society with no cognitive sequelae, 3 died of complications of acute liver failure except brain edema, and the remaining 6 were candidates for liver transplantation; 2 of them received living-related liver transplantation but 4 died without transplantation after discontinuation of therapy.

Conclusions

On-line hemodiafiltration was effective in patients with acute liver failure, and consciousness was maintained for the duration of artificial liver support, even in those in whom it was considered that hepatic function was completely abolished.     

Emergency cranial computed tomography in the management of acute febrile encephalopathy in children

OBJECTIVE: Evaluation of the influence of emergency cranial computed tomography on the management of acute febrile encephalopathy in children. METHODS: A retrospective study in children with acute febrile encephalopathy who underwent emergency cranial computed tomography within 12 hours of admission to the paediatric intensive care unit. All scans were evaluated by two independent radiologists. RESULTS: Thirty nine children were included. Fourteen scans were abnormal and two had clinically insignificant incidental findings. Four children with focal neurological signs had scans demonstrating extra-axial collections. None required neurosurgical intervention. Clinically, raised intracranial pressure was present in 10 patients. Only five had cerebral oedema on computed tomography; these five children died. Emergency cranial computed tomography influenced subsequent management in no child without focal neurological signs and in only one child with focal neurology. CONCLUSION: Emergency cranial computed tomography in acute febrile encephalopathy in children without focal neurological signs has little influence on subsequent management. Where cranial computed tomography is thought to be necessary, it should be carried out when the child's clinical condition has been stabilised.     

Fulminant liver failure due to severe veno-occlusive disease after haematopoietic cell transplantation: a depressing experience

BACKGROUND: Between 1988 and 2002, eight patients were referred to our unit from other institutions, for management of fulminant hepatic failure (FHF) complicating severe veno-occlusive disease (VOD). AIM: To review our experience with these patients. METHODS: Retrospective analysis of medical case notes. RESULTS: In 7/8 cases, a histological diagnosis of VOD was confirmed by transjugular liver biopsy or post-mortem examination. All had undergone high-dose chemotherapy. Cyclophosphamide was included in the conditioning regimen of six patients. All developed encephalopathy and four progressed to grade 3 or 4 encephalopathy. All patients died, none surviving >75 days after haematopoietic cell transplantation. Three were listed for liver transplantation: one underwent transplantation, and two died before transplantation could be performed. Two suffered significant complications of transjugular liver biopsy. One underwent transjugular intrahepatic porto-systemic venous stent (TIPS) insertion. DISCUSSION: FHF complicating severe VOD is associated with multi-organ failure, and has a very poor prognosis. Our experience and that described in published literature, questions the benefits of measures such as liver transplantation or prolonged intensive care.     

Managing patients with acute liver failure: developing a tool for practitioners

Patients with acute liver failure (ALF) are treated on the general intensive care unit (ICU) within this regional centre for hepatology and liver transplantation. This group of patients are at high risk of developing cerebral oedema, but because of the associated coagulopathy, intracranial pressure is not measured invasively. The safe management of these patients is vital to their outcome, and yet, there is no national or local guidance on the best practice for this group of patients. An absence of guidelines, or evidence base specific to caring for hepatology patients, was highlighted as we reviewed local clinical practices and those at other liver specialty centres, the British Liver Trust and published literature. We identified a need to develop evidence-based guidance for staff caring for patients with ALF within ICUs. A systematic approach enabled us to identify best practice to support the development of a structured evidence-based approach to care.     

Intensive care management of acute liver failure

PURPOSE OF REVIEW: The mortality of acute liver failure remains unacceptably high and liver transplantation is the only effective treatment available to date. This review focuses on new research developments in the field and aims to provide a pragmatic organ-based treatment approach for liver failure patients requiring intensive care support. RECENT FINDINGS: The pathophysiological basis for cerebral edema formation in acute liver failure continued to be the focus of various investigations. In-vivo observations confirmed the link between ammonia, cerebral glutamine content and intracranial hypertension. The role of arterial ammonia as an important prognostic indicator formed the basis of prospective, observational studies. Reduced monocytic HLA-DR expression linked acute liver failure with poor prognosis, and the cerebral effects and side effects of vasoactive therapy with terlipressin were investigated with two studies showing contradictory results. SUMMARY: Despite increased knowledge of the pathophysiological events leading to organ dysfunction in acute liver failure, supportive treatment options remain limited in their efficacy and largely noncurative.     

Outcome of Orthotopic Liver Transplantation in the Aetiological and Clinical Variants of Acute Liver Failure

Thirty-three patients with acute liver failure underwent orthotopicliver transplantation, including 16 with fulminant hepatic failure,15 with late–onset hepatic failure and two with severeacute liver failure (coagulopathy without encephalopathy). Twenty–three(70 per cent) survived to leave hospital and 21 of these arecurrently alive and well. Outcome correlated with the serumbilirubin level before transplantation (p<0.05) but no correlationwas found with the variant of acute liver failure, grade ofencephalopathy, cerebral oedema, serum creatinine, white cellcount, prothrombin time or platelet count at the time of transplantation.Severe coagulation factor deficiencies did not constitute aclinical problem. One patient developed a neurological deficitsecondary to cerebral oedema, but otherwise the morbidity reflectedthat observed in the general population after transplantation.Careful monitoring of intracranial pressure and surveillance(with early aggressive therapy) for bacterial and fungal infectionsis very important in achieving a successful outcome after transplantation.     

活体肝移植和尸体肝移植过程中患者肾功能的比较

背景:原位肝移植中诸多因素可导致移植后急性肾功能衰竭,但不同移植方式对移植过程中患者肾功能的影响并不清楚。目的:比较活体部分供肝移植和尸体全肝移植对移植过程中患者肾功能的影响。方法:纳入拟行活体部分供肝原位肝移植的晚期肝病患者15例设为活体组,采用背驮式原位肝移植;另与同期进行的尸体全肝移植20例患者设为尸体组,采用非转流经典原位肝移植。分别于切皮前即刻、切皮后1h、无肝期30min、新肝期1h及新肝期4h测定血流动力学和肾功能指标。结果与结论:两组患者各时间点平均动脉压、心率比较差异无显著性意义(P>0.05),活体组无肝期30min时心输出量、心指数高于尸体组,而体循环血管阻力、体循环血管阻力指数低于尸体组(P<0.05)。两组移植过程中各时点血清胱抑素C、β2-微球蛋白、肌酐及肌酐清除率均在正常范围内,总尿量及呋噻米用量比较差异无显著性意义(P>0.05),但活体组无肝期分钟尿量明显多于尸体组(P<0.05)。提示活体部分供肝移植和尸体全肝移植对移植过程中患者肾功能均未产生不利影响。     

Changes in the management of severe traumatic brain injury: 1991-1997

OBJECTIVE: To survey the management of head-injured patients in 1997 and to identify differences compared with a survey conducted in 1991. DESIGN: A two-page questionnaire was mailed to all neurosurgeons in North America certified by the American Board of Neurologic Surgeons, asking their views regarding the most appropriate acute care of patients with severe traumatic brain injury (TBI). SETTING: North American neurosurgical practices. PATIENTS: Not applicable. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared with a 1991 survey, there was a significant increase in the proportion of neurosurgeons who felt these patients should have intracranial pressure monitoring (28% vs. 83%) and a decrease in the proportion who used prophylactic hyperventilation therapy (83% vs. 36%) and steroids (64% vs. 19%). Ninety-seven percent of respondents felt that the cerebral perfusion pressure should be maintained at >70 mm Hg, and 44% indicated that patients with severe TBI should be treated at Level I trauma centers. CONCLUSIONS: There have been significant changes in the acute management of patients with severe TBI since 1991. Current practices more closely reflect the recommendations of evidence-based guidelines.     

Outcome of patients with cirrhosis admitted to intensive care

PURPOSE OF REVIEW: The incidence of cirrhosis is increasing exponentially and is associated with significant morbidity and mortality. This cirrhotic population is prone to infection, which is a frequent precipitant for the development of organ dysfunction; a syndrome often referred to as 'acute-on-chronic' liver failure. Historically, the perception of cirrhosis with organ dysfunction as having a poor prognosis has led to invariably iniquitous access to intensive care. Data to support this view, however, are lacking. RECENT FINDINGS: Acute variceal bleeding is associated with markedly improved survival and warrants organ support in intensive care. Survival correlates directly with the number of organs failing, with sepsis and multiorgan failure resulting in over 90% mortality. The requirement for renal replacement therapy confers a poor prognosis in patients not suitable for liver transplantation. SUMMARY: Admission to intensive care for many patients with cirrhosis is not futile, particularly for those with single organ dysfunction and acute variceal bleeding. It can be extremely challenging to manage patients with organ dysfunction and encephalopathy in a ward environment, and these patients frequently require, and indeed benefit from, augmented levels of care in high-dependency and intensive care environments.     

肝移植术前等待患者的死亡原因分析

目的 调查分析住院等待肝移植患者的死亡原因,为加强肝移植术前等待患者的管理提供方向和依据.方法 回顾性分析我院2003年1月-2007年6月住院等待肝移植手术期间死亡的63例患者等待时间、治疗过程和死亡原因.结果 63例患者的平均住院等待时间为(32.53±17.21)d,重症加强治疗病房(ICU)住院时间为(12.75±9.77)d.等待期间上消化道出血、意识障碍、感染的发生率分别为47.62%、39.68%和74.60%.主要死因感染性休克和感染性多器官功能衰竭(MOF)以及曲张静脉破裂出血的病死率分别为39.68%和26.98%.血液净化治疗对肝性脑病治疗有效.结论 当前肝移植术前等待住院患者的主要死亡原因是感染和致命性上消化道出血.     

Intensive-care unit experience in the Mayo liver transplantation program: the first 100 cases

The first 100 liver transplantations at the Mayo Clinic were performed in 83 patients, who required a total of 917 patient days in the intensive-care unit (ICU). The mean duration of stay in the ICU was 5.91 days after liver transplantation and 6.15 days for patients who subsequently required readmission to the ICU. During the immediate postoperative period, hypothermia and hyperglycemia invariably occurred. Later during the initial admission or on readmission to the ICU, there arose the possibility of infections and renal insufficiency. Prompt diagnosis and treatment are necessary for hypertension, hypokalemia, severe metabolic alkalosis, fever, altered mental status, oliguria, and signs of graft failure in liver transplant patients. In our patient series, selective bowel decontamination minimized the occurrence of gram-negative and fungal sepsis, and use of antihypertensive agents and correction of coagulopathies may have decreased the risk of intracranial bleeding in patients with hypertension and clotting defects. Anticipation of potential conditions postoperatively and early implementation of treatment are key factors in the successful ICU management of patients who have undergone liver transplantation.     

Therapeutic hypothermia for treatment of intractable intracranial hypertension after liver transplantation

A comatose 23-year-old woman with acute liver failure due to an overdose of acetaminophen had indications of intracranial hypertension and underwent liver transplantation. Her level of arousal did not improve, and on postoperative day 1, clinical signs of cerebral herniation became apparent. An intracranial pressure monitor was placed, and intracranial hypertension was documented. Elevations in intracranial pressure persisted despite maximal osmotherapy, and therapeutic hypothermia was started. Normalization of intracranial pressure was rapid. Findings on neurological examination improved and the patient was discharged from the hospital with no neurological impairment.     

Hepatic encephalopathy mimicking stroke. A case report.

This case demonstrates focal neurologic deficit mimicking stroke with underlying hepatic encephalopathy. Unilateral weakness in patients with hepatic encephalopathy has not been previously described in the English language literature. A 46-yr-old white woman was admitted to an acute care hospital for left shoulder manipulation, underwent general anesthesia and appeared to have had a right cerebrovascular accident. At transfer to the rehabilitation hospital, in addition to the left hemiparesis, there were inconsistencies in the neurologic examination and signs of cognitive impairment and liver failure. The patient's response to an intensive, multidisciplinary inpatient rehabilitation program along with treatment of the liver dysfunction led to resolution of left-sided weakness and flapping tremor with independence in ambulation and activities of daily living. Relevant literature is reviewed. A thorough history and physical examination with liver function assessment should always be performed in patients with cerebrovascular accident and unusual recovery.     

Acetaminophen poisoning: an update for the intensivist

Acetaminophen overdose is common and can result from deliberate/nonstaggered or accidental/staggered ingestion. Patients presenting within 24 h of an acetaminophen overdose can safely be managed on medical wards. Early management of nonstaggered overdose is guided by the plasma acetaminophen concentration, whereas management of accidental/staggered ingestion is guided by ingested dose. Ingested dose and time from ingestion to presentation are important prognostic factors in accidental/staggered ingestion. Acetaminophen-induced acute liver failure (ALF) requires meticulous supportive care in an intensive care unit (ICU), with early identification and transfer of patients who are likely to require liver transplantation to a specialist liver centre. The modified King's College Hospital criteria (incorporating lactate into the traditional criteria) represent the best tool for identifying patients who require transplantation.