Constantine J. Karvellas, MD, FRCPC; Fred Pink, MBBS; Mark McPhail, MBBS, PhD; Mark Austin, MBBS; Georg Auzinger, MBBS; William Bernal, MBBS, MD; Elizabeth Sizer, MBBS; Demetrios J.Kutsogiannis, MD, FRCPC; Ian Eltringham, MBBS; Julia A. Wendon, MBChB, FRCP
Objectives: To determine what physiological and biochemical factors predict development of bacteremia in nontransplanted patients with acute on chronic liver failure and, on diagnosis of bacteremia, what is the natural history of bacteremic patients versus control subjects (acute on chronic liver failure). Interventions:None. Design: Retrospective analysis of data collected prospectively and entered into a dedicated physiology database. Setting: Specialist liver intensive therapy unit. Patients: Critically ill non-transplanted patients with acute on chronic liver failure admitted between January 2003 and July 2005. Measurements and Main Results: One hundred eighty-four patients were deﬁned with acute on chronicliver failure; 67 (36%) had bacteremia. One hundred seventeen (64%) patients did not (acute on chronic liver failure). Fifty-eight percent of isolates were Gram-negative organisms, 36% were Gram-positives, and 6% fungemia. Median time to ﬁrst bacteremia was 8 days (range, 3–12 days). On admission (univariate), bacteremic patients had signiﬁcantly higher Modiﬁed End Stage Liver Disease scores (27vs. 24, p .037), Acute Physiology and Chronic Health Evaluation II scores (23 vs. 21, p .049), and greater degrees of encephalopathy (Glasgow Coma Scale score 10 vs. 12, p .001). During their liver intensive therapy unit course, bacteremic patients had signiﬁcantly greater requirements for renal replacement therapy (64% vs. 49%, p .043), mechanical ventilation (88% vs. 68%, p .002), and a longermedian liver intensive therapy unit stay (16 vs. 5 days, p < .001). Survival to hospital discharge was worse in the bacteremic group (25% vs. 56%, p < .001). Multivariate analysis (logistic regression) was performed separately modeling with Acute Physiology and Chronic Health Evaluation II and Modiﬁed End Stage Liver Disease. In the ﬁrst model, Acute Physiology and Chronic Health Evaluation II (oddsratio 1.24) and bacteremia (2.24) were independent predictors of mortality. In the later model, Modiﬁed End Stage Liver Disease (odds ratio, 1.06), requirement for renal replacement therapy (3.08), Glasgow Coma Scale (0.72), and bacteremia (2.30) were signiﬁcant. Both models performed similarly (Modiﬁed End Stage Liver Disease area under the receiver operating characteristic curve, 0.864; AcutePhysiology and Chronic Health Evaluation II, 0.862). Conclusions: In nontransplanted patients with acute on chronic liver failure, bacteremia was associated with increased severity of illness on admission, greater requirements for organ support, and independently adversely impacted on survival. Higher Acute Physiology and Chronic Health Evaluation II and Modiﬁed End Stage Liver Disease scores werealso independently predictive of mortality. (Crit Care Med 2010; 38:121–126) KEY WORDS: cirrhosis; sepsis; bacteremia; modiﬁed end stage liver disease; APACHE II; systemic inﬂammatory response syndrome
atients with acute on chronic liver failure (ACLF) are abnormally susceptible to infection as a result of immunologic deﬁcits in cirrhosis. These patients have defects in both humoral
andcell-mediated immunity. Mechanisms previously described include decreased hepatic production of complement (reduced C3 and C5 levels), impaired Kupffer cell function (phagocytosis), altered neutrophil chemotaxis (presence of
From the Division of Critical Care Medicine (CJK, DJK), University of Alberta, Edmonton, Canada; and Institute of Liver Studies (CJK, FP, MM, MA, GA, WB, ES, IE, JAW),...