Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy

doi:10.1016/j.jcrc.2009.01.008

Journal of Critical Care

Volume 24, Issue 3, September 2009, Pages 364-370

https://doi.org/10.1016/j.jcrc.2009.01.008 Get rights and content

Abstract

Purpose

Data regarding outcome of patients with chronic liver disease with severe hepatic encephalopathy in intensive care unit are currently scarce.

Methods

This study is a retrospective observational case series in a medical intensive care unit (ICU) in a university hospital from 1995 to 2005. Patients with hepatic encephalopathy (HE) (admitted with or developing) were identified. Clinical and laboratory parameters were analyzed to determinate predictors of ICU and 1-year mortality.

Results

Seventy-one patients were included (53 male). Median Simplified Acute Physiology Score was 56 with Child-Pugh score 11 ± 2. Seventy-six percent of patients were admitted with coma (Glasgow Coma Scale, 7.7 ± 4). Eighty-two percent of patients required intubation, and 28% vasopressors. Thirty-five percent died during ICU stay. At 1 year, mortality was 54%. Univariate analysis identified arterial hypotension, mechanical ventilation, vasopressors at any time, acute renal failure, Simplified Acute Physiology Score, and sepsis associated with ICU mortality. In multivariate analysis, vasopressor use or acute renal failure was the main independent predictor of ICU death and 1-year mortality. Patients free of these risk factors, even requiring intubation, were identified as isolated HE, with lower mortality rates.

Conclusion

Predictors of outcome were similar to other groups of patients with liver disease admitted for other reasons. Intensive care unit mortality was lower than reported for other groups of patients with similar illness. Patients with severe HE admitted to ICU with no organ dysfunction other than mechanical ventilation had a better outcome and may require ICU admission.

Introduction

Liver disease and particularly cirrhosis are important causes of mortality and morbidity in hospitalized patients. A number of medical complications may prompt admission of patients with cirrhosis to the intensive care unit (ICU) [1]. Hepatic encephalopathy (HE) may complicate acute or chronic liver disease [2]. This complication may be sometimes totally reversible with symptomatic treatment [3], [4]. Despite a better understanding of the disease, data regarding the prognostic of ICU patients are currently lacking. It has previously been reported that patients with cirrhosis have a poor outcome, associated with the use of a high amount of health care resources [5], [6], [7]. Consequently, the decision to use invasive therapies, including mechanical ventilation, is often questioned in this population. The objective of the study was to evaluate ICU and 1-year mortality of patients with severe HE and factors associated with poor outcome.

Section snippets

Methods

We reviewed the charts for all consecutive patients older than 18 years who were admitted to the medical ICU in a university hospital from January 1995 to December 2005. Because the study design was strictly retrospective and observational, with no drug or technique being administered for the purpose of the study, and in accordance with French regulations on biomedical research, no informed consent was obtained. Diagnosis of HE was made at admission or during stay. A total of 71 patients were

Results

Main indication for ICU admission was coma in 54 cases (76%, associated with severe sepsis in 5 patients). Others were septic shock or severe sepsis (n = 7, 9.8%), gastrointestinal bleeding (n = 4), or pancreatic disease (n = 4). Population is detailed in Table 1. Median age was 58 years (range, 30-80 years). There were 55 patients (77%) admitted with an initial suspicion of HE, and 58 patients (81%) required intubation, mostly for airway protection. Acute renal failure was found in 19 patients

Discussion

We found that patients with severe HE had a 35% ICU mortality rate (39.5% hospital mortality). Based on literature data and expected mortality from SAPSII, mortality seemed lower than other groups of patients with liver disease admitted to the ICU for other reasons. This may suggest that patients may benefit from ICU care. Moreover, mortality was even lower for patients free of another organ dysfunction than mechanical ventilation because most patients required intubation for airway protection

Acknowledgments

The authors thank Dr L. Mitchell-Heggs for help in preparation of the final manuscript.

References (28)

BleiA.T. et al.
Hepatic encephalopathy
Am J Gastroenterol
(2001)
WrightG. et al.
Management of hepatic encephalopathy in patients with cirrhosis
Best Pract Res Clin Gastroenterol
(2007)
BoneR.C. et al.
Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine
Chest
(1992)
GinèsP. et al.
Hepatorenal syndrome
Lancet
(2003)
AggarwalA. et al.
Predictors of mortality and resource utilization in cirrhotic patients admitted to the medical ICU
Chest
(2001)
BenhaddouchZ. et al.
Mortality and prognostic factors of the cirrhotic patients with hepatic encephalopathy admitted to medical intensive care unit
Ann Fr Anesth Reanim
(2007)
WehlerM. et al.
Short-term prognosis in critically ill patients with cirrhosis assessed by prognostic scoring systems
Hepatology
(2001)
OngJ.P. et al.
Correlation between ammonia levels and the severity of hepatic encephalopathy
Am J Med
(2003)
WongF. et al.
Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club
Gut
(2005)
Peter FerenciA.L. et al.
Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the Working Party at the 11th World Congresses of Gastroenterology, Vienna, 1998
Hepatology
(2002)

ShellmanR.G. et al.

Prognosis of patients with cirrhosis and chronic liver disease admitted to the medical intensive care unit

Crit Care Med

(1988)

KressJ.P. et al.

Outcomes of critically ill patients denied consideration for liver transplantation

Am J Respir Crit Care Med

(2000)

SinghN. et al.

Outcome of patients with cirrhosis requiring intensive care unit support: prospective assessment of predictors of mortality

J Gastroenterol

(1998)

Le GallJ.R. et al.

The Logistic Organ Dysfunction system. A new way to assess organ dysfunction in the intensive care unit. ICU Scoring Group

JAMA

(1996)

Cited by (91)

Managing cirrhosis with limited resources: perspectives from sub-Saharan Africa
2024, The Lancet Gastroenterology and Hepatology
Cirrhosis represents the end stage of chronic liver disease. Sub-Saharan Africa, a resource-constrained region, has a high burden of chronic liver disease, with causes including chronic viral hepatitis, excessive alcohol use, and metabolic dysfunction-associated steatotic liver disease (MASLD), the risk of which is burgeoning. The development of liver cirrhosis predicts for morbidity and mortality, driven by both liver dysfunction and the consequences of portal hypertension. Compensated cirrhosis portends a better prognosis than decompensated cirrhosis, highlighting the need for the early diagnosis of cirrhosis and its causes. With resource challenges, the diagnosis and management of cirrhosis is demanding, but less costly and less invasive interventions with substantial benefits, ranging from simple blood tests to transient elastography, are feasible in such settings. Simple interventions are also available to manage the complex manifestations of decompensation, such as β blockers in variceal bleeding prophylaxis, salt restriction and appropriate diuretic use in ascites, and lactulose and generic rifaximin in hepatic encephalopathy. Ultimately, managing the underlying causative factors of liver disease is key in improving prognosis. Management demands expanded policy interventions to increase screening and treatment for hepatitis B and C and reduce alcohol use and the metabolic factors driving MASLD. Furthermore, the skills needed for more specialised interventions, such as transjugular intrahepatic portosystemic shunt procedures and even liver transplantation, warrant planning, increased capacity, and support for regional centres of excellence. Such centres are already being developed in sub-Saharan Africa, demonstrating what can be achieved with dedicated initiatives and individuals.
Intensive Care Unit Care of a Patient with Cirrhosis
2023, Medical Clinics of North America
Overview of oxidative stress findings in hepatic encephalopathy: From cellular and ammonium-based animal models to human data
2022, Analytical Biochemistry
Citation Excerpt :
Epidemiological studies have found that decreased albumin level together with irreversibly oxidized albumin (HNA2) are an independent predictors of mortality [22–26]. The increase of mortality rate of HE patients with hypoalbuminemia has been previously shown and was accounted for 6.7–10.9% for short period of hospitalization and about 42.8–73.9% for the long-term follow up [17–21]. Recent studies demonstrated that long-term human albumin infusion improves the prognosis of cirrhotic patients by lowering the overall mortality and the likelihood of emergent hospitalizations [25,26].
Oxidative stress is a natural phenomenon in the body. Under physiological conditions intracellular reactive oxygen species (ROS) are normal components of signal transduction cascades, and their levels are maintained by a complex antioxidants systems participating in the in-vivo redox homeostasis. Increased oxidative stress is present in several chronic diseases and interferes with phagocytic and nervous cell functions, causing an up-regulation of cytokines and inflammation. Hepatic encephalopathy (HE) occurs in both acute liver failure (ALF) and chronic liver disease. Increased blood and brain ammonium has been considered as an important factor in pathogenesis of HE and has been associated with inflammation, neurotoxicity, and oxidative stress. The relationship between ROS and the pathophysiology of HE is still poorly understood. Therefore, sensing ROS production for a better understanding of the relationship between oxidative stress and functional outcome in HE pathophysiology is critical for determining the disease mechanisms, as well as to improve the management of patients.
This review is emphasizing the important role of oxidative stress in HE development and documents the changes occurring as a consequence of oxidative stress augmentation based on cellular and ammonium-based animal models to human data.
Abnormal brain oxygen homeostasis in an animal model of liver disease
2022, JHEP Reports
Increased plasma ammonia concentration and consequent disruption of brain energy metabolism could underpin the pathogenesis of hepatic encephalopathy (HE). Brain energy homeostasis relies on effective maintenance of brain oxygenation, and dysregulation impairs neuronal function leading to cognitive impairment. We hypothesised that HE is associated with reduced brain oxygenation and we explored the potential role of ammonia as an underlying pathophysiological factor.
In a rat model of chronic liver disease with minimal HE (mHE; bile duct ligation [BDL]), brain tissue oxygen measurement, and proton magnetic resonance spectroscopy were used to investigate how hyperammonaemia impacts oxygenation and metabolic substrate availability in the central nervous system. Ornithine phenylacetate (OP, OCR-002; Ocera Therapeutics, CA, USA) was used as an experimental treatment to reduce plasma ammonia concentration.
In BDL animals, glucose, lactate, and tissue oxygen concentration in the cerebral cortex were significantly lower than those in sham-operated controls. OP treatment corrected the hyperammonaemia and restored brain tissue oxygen. Although BDL animals were hypotensive, cortical tissue oxygen concentration was significantly improved by treatments that increased arterial blood pressure. Cerebrovascular reactivity to exogenously applied CO₂ was found to be normal in BDL animals.
These data suggest that hyperammonaemia significantly decreases cortical oxygenation, potentially compromising brain energy metabolism. These findings have potential clinical implications for the treatment of patients with mHE.
Brain dysfunction is a serious complication of cirrhosis and affects approximately 30% of these patients; however, its treatment continues to be an unmet clinical need. This study shows that oxygen concentration in the brain of an animal model of cirrhosis is markedly reduced. Low arterial blood pressure and increased ammonia (a neurotoxin that accumulates in patients with liver failure) are shown to be the main underlying causes. Experimental correction of these abnormalities restored oxygen concentration in the brain, suggesting potential therapeutic avenues to explore.
Efficacy and Safety of Ornithine Phenylacetate for Treating Overt Hepatic Encephalopathy in a Randomized Trial
2021, Clinical Gastroenterology and Hepatology
Citation Excerpt :
The length of hospitalization and/or ICU stay can be affected by HE status, but also by other medical or social factors; thus, the primary outcome remained time to clinical improvement. Because of the substantial morbidity, mortality, and economic burden of hospitalizations, outcomes such as the median time to discharge from the ICU and length of hospital stay were assessed.1–3,5–7 Although the overall median time to hospital discharge was similar between the 2 groups, the median time to discharge from the ICU occurred approximately 1.5 days sooner for patients who received OP vs placebo.
Hepatic encephalopathy (HE) is associated with increased morbidity, mortality, and health care resource use. In this phase 2b study, we evaluated the efficacy and safety of ornithine phenylacetate (OP), an ammonia scavenger, in hospitalized patients with cirrhosis, increased levels of ammonia at screening, and acute or overt HE.
We conducted a double-blind study of 231 patients with cirrhosis and HE at multiple sites in North America, Europe, Israel, and Australia from January 7, 2014, through December 29, 2016. Patients were assigned randomly to groups that received placebo or OP (10, 15, or 20 g/d, based on the severity of liver disease), plus each institution’s standard of care (eg, lactulose to achieve 2–3 bowel movements with or without rifaximin, in accordance with guidelines). The primary end point was time to confirmed clinical response, defined as reduction to HE staging tool (HEST) stage 2 from baseline HEST stages 3/4 or improvement to HEST stages 0/1 from baseline stage 2, in the intent-to-treat population (all patients with increased levels of ammonia at screening, determined by a local laboratory).
Median times to clinical improvement, based on ammonia measurements at local laboratories, did not differ significantly between the groups given OP vs the placebo group (P = .129). Analyses of central laboratory–confirmed increases in levels of ammonia at baseline (n = 201) showed clinical improvement in HE at a median of 21 hours sooner in groups given OP vs placebo. The percentages of patients with any specific adverse event did not differ significantly between groups. Serious adverse events occurred in 25% of patients in the OP group and in 29% in the placebo group (P = .552).
In a randomized controlled trial of patients with cirrhosis and HE, we found no significant difference in time to clinical improvement between patients given OP vs placebo. However, OP appears to be safe and should undergo further testing for treatment of hyperammonemia in hospitalized patients receiving treatment for the underlying precipitant of acute or overt HE. ClinicalTrials.gov no: NCT01966419.
Clinical Manifestations of Hepatic Encephalopathy
2020, Clinics in Liver Disease
Citation Excerpt :
In many cases, it is difficult to identify the exact onset because the initial symptoms are subtle; however, it remains a clinical landmark in patients with advanced disease.1 Although it may initially present as minimal symptoms that can be managed, it is associated with a poor prognosis, because patients that progress to severe HE have increased mortality, with some studies showing an increase of greater than 50% mortality in the first year alone.2,3 The symptoms of HE mainly affect the patient’s mental status, musculoskeletal system, and mood/behavior.4

View all citing articles on Scopus

^☆: No funding support was received for this work. None of the authors are involved in any commercial or noncommercial affiliations or consultancies that are, or may be perceived to be, in conflict of interest with the work.

View full text

Prognosis and 1-year mortality of intensive care unit patients with severe hepatic encephalopathy☆

Abstract

Purpose

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgments

Am J Gastroenterol

Best Pract Res Clin Gastroenterol

Chest

Lancet

Chest

Ann Fr Anesth Reanim

Hepatology

Am J Med

Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club

Gut

Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the Working Party at the 11th World Congresses of Gastroenterology, Vienna, 1998

Hepatology

Prognosis of patients with cirrhosis and chronic liver disease admitted to the medical intensive care unit

Crit Care Med

Outcomes of critically ill patients denied consideration for liver transplantation

Am J Respir Crit Care Med

Outcome of patients with cirrhosis requiring intensive care unit support: prospective assessment of predictors of mortality

J Gastroenterol

The Logistic Organ Dysfunction system. A new way to assess organ dysfunction in the intensive care unit. ICU Scoring Group

JAMA