Elsevier

Journal of Critical Care

Volume 24, Issue 3, September 2009, Pages 453-457
Journal of Critical Care

Influence of mild therapeutic hypothermia on the inflammatory response after successful resuscitation from cardiac arrest

https://doi.org/10.1016/j.jcrc.2008.10.012Get rights and content

Abstract

Purpose

Although animal studies document conflicting data on the influence of hypothermia on cytokine release in various settings, no data exist if hypothermia affects the inflammatory response after successful cardiopulmonary resuscitation.

Materials and Methods

Arrest- and treatment-related variables of 71 patients were documented, and serum samples were analyzed for levels of interleukin 6, tumor necrosis factor-α, C-reactive protein, and procalcitonin immediately after hospital admission and after 6, 24, and 120 hours. At day 14, patients were dichotomized in those with good and bad neurological outcome.

Results

Regardless of outcomes, interleukin 6 levels were significantly elevated by the use of hypothermia (n = 39). The rate of bacterial colonization was significantly higher in hypothermic patients (64.1 vs 12.5 %; P < .001). On the contrary, procalcitonin levels were, independent of the use of hypothermia, only significantly elevated in patients with bad neurological outcome. Hypothermic patients showed a strong trend to reduced mortality. However, there was no influence on neurological recovery.

Conclusions

In this observational study, hypothermia influenced the inflammatory response after cardiopulmonary resuscitation and lead to a higher rate of bacterial colonization without altering ultimate neurologic recovery.

Introduction

After successful cardiopulmonary resuscitation (CPR) from out-of-hospital cardiac arrest (OHCA) in patients who have ventricular fibrillation (VF), the use of mild therapeutic hypothermia (MTH) is advocated to reduce neurologic dysfunction [1]. Although survivors of OHCA exhibit a systemic inflammatory response [2], some animal data suggest that MTH does not alter this cascade [3]. In settings other than CPR, the use of hypothermia yielded conflicting results, and experimentally, MTH is associated with a marked increase of proinflammatory cytokines, which is linked to brain and heart failure [4], [5], [6]. Although cytokine activation is essential for optimal immune response to microbial pathogens, excessive production can also induce shock and progression of organ failure leading to death [7], [8]. In this preliminary study, we compared the time course of the inflammatory cytokines interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and the biomarkers C-reactive protein (CRP) and procalcitonin (PCT) in patients resuscitated from OHCA and treated with or without MTH. We hypothesized that the use of MTH would result in increased serum cytokine and biomarker levels.

Section snippets

Material and methods

Seventy-one patients (>18 years) with nontraumatic arrest cause were enrolled in this observational study. Demographical and CPR-related data were collected at the emergency department immediately after hospital admission and after 6, 24, and 120 hours at the intensive care unit using a Web-based data entry system as part of a quality assurance initiative of the German Society of Anesthesia and Intensive Care Medicine [9]. At the same time, serum samples for the determination of IL-6, TNF-α,

Results

No differences between patients treated with or without MTH were found with regard to most of the demographical and arrest-related data (Table 2). Patients treated with MTH were significantly more prone to bacterial colonization and required significantly more often catecholamines to maintain arterial pressures (Fig. 1). Bacterial colonization was predominantly found in bronchoalveolar lavage (48.8% of all cases), blood cultures (30.2%), and urine (11.6%), with Gram-positive cocci (58.5%) and

Discussion

Survivors of OHCA exhibit a “sepsis like syndrome” including high levels of circulating cytokines, which are associated with dismal outcomes [2]. Our results are in accordance with this observation and extend our knowledge in that MTH per se results in significant alterations in IL-6, CRP, and PCT levels. In settings of regional ischemia/reperfusion injury in the central nervous system, that is, acute ischemic stroke, there is evidence that high IL-6 serum levels are associated with early

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This study was supported by a grant to Dr Michael Fries from the Laerdal Foundation for Acute Medicine, Stavanger, Norway. Test kits for the determination of Procalcitonin and C-reactive protein serum levels were kindly provided by BRAHMS AG, Hennigsdorf, Berlin, Germany. Michael Fries has received honoraria as speaker by the same company.

1

These authors contributed equally to this study.

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