Discussion
In this paper, we found a significant association between longer
duration of mild hypothermia and good neurological outcome at discharge.
This finding supports the hypothesis that early mild hypothermia exerts
a positive effect on neurological outcome in VA-ECMO patients. This
observation stands true even after excluding post-cardiotomy patients
who did not experience cardiac arrest. Interestingly, mild hypothermia
did not influence in-hospital mortality. Although one may hypothesize
that bleeding may be exacerbated with ECMO-associated coagulopathy in
addition to hypothermia, this was not found to be the case.
We previously showed that early hyperoxia was a strong marker of poor
neurological outcome in VA-ECMO patients.14 In this
study, hypothermia proved to be yet another significant factor in
neurological outcome, after adjusting for important risk factors
including hyperoxia, suggesting temperature management may be an early
intervention that improves neurological outcome in this population.
Nevertheless, despite our findings, there is conflicting evidence
regarding the benefit of therapeutic hypothermia in ECMO patients. In
agreement with our study, in a pooled analysis of 13 studies, Chen et
al. found a significant association between hypothermia (32–34°C) and
favorable neurologic outcomes, defined by a cerebral performance
category of 1–2.15 In contrast, a recent
meta-analysis of 35 studies showed that among extracorporeal
cardiopulmonary resuscitation (eCPR) patients, survival and neurological
outcomes were not different between patients who underwent therapeutic
hypothermia (ranging between 33-36°C) and patients who did
not.16 However, these reports, unlike our study, were
limited by high heterogeneity of included studies without granular
temperature data.
Furthermore, the data on the effect of mild hypothermia in non-eCPR
VA-ECMO patients is sparse. While limited data exists regarding the
benefit of early, therapeutic hypothermia in ECMO patients, a
physiologic explanation for why it might be beneficial can be opined for
all 3 cohorts, eCPR, cardiogenic shock, and post-cardiotomy shock.
Reperfusion injury secondary to prolonged low flow in eCPR patients
portends a significant neurological injury, which may be mitigated by
TTM.17 Also, hypothermia may offer hemodynamic
benefits following cardiogenic shock including reduced metabolic rate,
increased contractility, and increased cardiac
output.18,19 A similar advantageous hemodynamic
profile could result in improved neurological outcomes in
post-cardiotomy shock patients. This study provides supporting evidence
that even in the non-eCPR patients, mild hypothermia was associated with
good neurological outcome. Therefore, our study is
hypothesis-generating, necessitating further research on hypothermia in
each VA-ECMO indication.
This study has several limitations. It is a single center observational
study. We included ECMO patients with different indications such as
cardiac arrest, cardiogenic shock, and post-cardiotomy shock. However,
we performed a sensitivity analysis to exclude patients with cardiac
arrest and the and the benefit to hypothermia persisted. Given the
limited sample size, a multi-center study is necessary to study this
question in each VA-ECMO indication. Despite the small sample size, a
beneficial effect of hypothermia was large on neurological outcome.