Intensive Care of Patients With Acute Liver Failure: Recommendations of the U.S. Acute Liver Failure Study Group

R. Todd Stravitz, MD; Andreas H. Kramer, MD, MSc; Timothy Davern, MD; A. Obaid S. Shaikh, MD; Stephen H. Caldwell, MD; Ravindra L. Mehta, MD; Andres T. Blei, MD; Robert J. Fontana, MD; Brendan M. McGuire, MD; Lorenzo Rossaro, MD; Alastair D. Smith, MD; William M. Lee, MD; the Acute Liver Failure Study Group


Crit Care Med. 2007;35(11):2498-2508. 

In This Article

Abstract and Introduction

Objective: To provide a uniform platform from which to study acute liver failure, the U.S. Acute Liver Failure Study Group has sought to standardize the management of patients with acute liver failure within participating centers.
Methods: In areas where consensus could not be reached because of divergent practices and a paucity of studies in acute liver failure patients, additional information was gleaned from the intensive care literature and literature on the management of intracranial hypertension in non-acute liver failure patients. Experts in diverse fields were included in the development of a standard study-wide management protocol.
Measurements and Main Results: Intracranial pressure monitoring is recommended in patients with advanced hepatic encephalopathy who are awaiting orthotopic liver transplantation. At an intracranial pressure of ≥ 25 mm Hg, osmotic therapy should be instituted with intravenous mannitol boluses. Patients with acute liver failure should be maintained in a mildly hyperosmotic state to minimize cerebral edema. Accordingly, serum sodium should be maintained at least within high normal limits, but hypertonic saline administered to 145-155 mmol/L may be considered in patients with intracranial hypertension refractory to mannitol. Data are insufficient to recommend further therapy in patients who fail osmotherapy, although the induction of moderate hypothermia appears to be promising as a bridge to orthotopic liver transplantation. Empirical broad-spectrum antibiotics should be administered to any patient with acute liver failure who develops signs of the systemic inflammatory response syndrome, or unexplained progression to higher grades of encephalopathy. Other recommendations encompassing specific hematologic, renal, pulmonary, and endocrine complications of acute liver failure patients are provided, including their management during and after orthotopic liver transplantation.
Conclusions: The present consensus details the intensive care management of patients with acute liver failure. Such guidelines may be useful not only for the management of individual patients with acute liver failure, but also to improve the uniformity of practices across academic centers for the purpose of collaborative studies.

Acute liver failure (ALF), defined as the onset of hepatic encephalopathy and coagulopathy within 26 wks of jaundice in a patient without preexisting liver disease, remains one of the most dramatic and highly mortal of all human afflictions. Nevertheless, the optimal management of patients with ALF remains very poorly defined and center-specific. Several reasons underlie the heterogeneous management of ALF, including the fact that ALF is a syndrome rather than a disease, representing the final manifestation of numerous etiologies. In addition, the syndrome is extremely difficult to study because of its high mortality and rarity (2,000 U.S. cases per yr).[1]

The Adult U.S. Acute Liver Failure Study Group (ALFSG) was founded in 1997 to define the epidemiology and management of patients with ALF. Since its inception, the group has collected data on > 1,100 patients with ALF from 23 prominent liver transplant centers. To more uniformly manage patients with ALF at participating centers, the ALFSG convened in December 2005 to review the available literature on the management of ALF, to compare the intensive care of patients with intracranial hypertension of various etiologies, and to compare practices within participating centers. Investigators in specialties outside of hepatology-including neuro-intensive care, nephrology, and coagulation-were invited to participate in formulating a standard study-wide management protocol. Where possible, the protocol was based upon literature pertaining to patients with ALF; where studies specifically examining ALF did not exist, management recommendations were derived from other literature. Recommended measures were defined as those in which evidence-based studies suggest possible benefit in the clinical course or outcome of patients with ALF. Measures without supporting clinical data, but which potentially may be of benefit based upon a reasonable rationale, or supported by literature not specifically pertaining to patients with ALF, were deemed insufficient data to recommend. Finally, measures which clinical studies suggest may be detrimental were not recommended. The protocol was approved by the 23 member sites on September 23, 2006, and revisions were approved on May 10, 2007.

The present protocol expounds on a previous position paper[2] sanctioned by the American Association for the Study of Liver Diseases. The position paper offers general guidelines targeted at nonintensivists, and is cited within the present protocol for completeness and to avoid duplication of publication.


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