Therapeutic hypothermia in acute liver failure: A multicenter retrospective cohort analysis.

Abstract

TO THE EDITOR: I read with interest the retrospective evaluation of therapeutic hypothermia (TH) in acute liver failure (ALF) by Karvellas et al.1 In the summary of key results, the authors indicate that TH may potentially be associated with benefits in patients younger than 26 years old with acetaminophen (APAP)–related ALF, and subsequently, they conclude that the data largely suggest no benefit of TH but also no harm. However, the data show a statistically significant deleterious effect on patients older than 63 years old with APAP ALF (odds ratio, <1.0; 95% confidence interval, 0.028‐0.999; ie, it did not cross unity). Moreover, when we plotted the odds ratio versus the patient age from Supporting Table 1 from the online version of their article, a striking inverse relationship between a TH effect and patient age was observed: no benefit in middle‐aged patients and a significant deleterious effect of TH in older patients (Fig. 1; r2 = 0.97).Figure 1: Inverse relation between the patient age and the odds ratio. Dark circles denote a statistically significant protective effect of therapeutic hypothermia for patients aged 18 to 25 years and a statistically significant deleterious effect of therapeutic hypothermia for patients 64 years old or older. Unfilled circles represent non‐significant protective nor deleterious effect.Older patients have impaired hepatic regeneration (see Schmucker and Sanchez2 for a review). The inverse relation found in the study by Karvellas et al.1 suggests that TH may augment the effect of aging in reducing the capacity for hepatic regeneration; this is a plausible explanation for the deleterious effect observed by the investigators in older patients with APAP ALF. The data of Karvellas et al.1 suggest that TH should be avoided in older patients with ALF until the safety of TH in older patients is established. Indeed, because the majority (>80%) of APAP‐related ALF patients are older than 23 years,3 the observation of Karvellas et al. of a deleterious effect in older APAP patients may warrant a cautionary comment in the guidelines for the management of ALF.4 A more balanced conclusion from Karvellas et al.'s study1 is that although TH may benefit very young adults with APAP ALF, the data suggest that hypothermia may be deleterious in older patients with APAP ALF; also, both effects require further comparative and safety studies with normothermia. The accompanying editorial comments that TH does not impair hepatic regeneration because there were no differences in spontaneous (transplant‐free) survival between TH patients and controls.5 However, hepatic regeneration was not measured in this study. Survival in ALF is a function covariant with myriad variables, including the stage at diagnosis, etiology, and quality of care.