Early achievement of mild therapeutic hypothermia and the neurologic outcome after cardiac arrest

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Abstract

Background

Mild therapeutic hypothermia (MTH) achieved by endovascular cooling has emerged as a new treatment strategy to reduce hypoxic brain injury after cardiac arrest (CA). It remains to be established how the time interval between CA and MTH impacts the neurologic outcome. We hypothesized that a more rapid achievement of MTH (time to target temperature [TTT], time to coldest temperature [TCT]) improves the outcome after CA.

Methods

Forty-nine consecutive patients successfully resuscitated from CA were enrolled. MTH with a body core temperature between 32.0 and 34.0 °C (target temperature: 33.0 °C) over 24 h was achieved using a closed-loop endovascular system. Based on the neurologic outcome at discharge, the patient group was dichotomized into good (no/mild cerebral disability) and poor (severe disability, coma/vegetative state, brain death) outcomes. Serum neurone specific enolase (NSE) as biochemical marker of brain damage was sampled at 24, 48, and 72 h after CA.

Results

Twenty-eight patients were discharged with a good outcome. Multivariate stepwise regression showed TTT (odds ratio for every h TTT: 0.69 [95% confidence interval: 0.51–0.98]) or, if entered into the model, TCT (odds ratio for every h TCT: 0.72 [95% confidence interval: 0.56–0.94]) to be independent predictors for good outcome. Further independent determinants were age, BMI, asystole as presenting rhythm, and thrombolysis during resuscitation. However, TCT was the only variable to correlate with maximum NSE values after CA (r = 0.32, P < 0.05).

Conclusions

Early achievement of MTH by endovascular cooling appears to reduce hypoxic brain injury and to favour a good neurologic outcome after CA.

Introduction

Over the past decades, the prognosis after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) has remained poor [1], [2]. Those who survive the devastating event, often retain a hypoxic brain injury and a permanently incapacitating neurologic deficit. Recently, mild therapeutic hypothermia (MTH) with a recommended reduction of body core temperature (T) to 33 °C over 12 to 24 h [3] has emerged as a new treatment strategy. Feasibility and safety of MTH have been assessed in several clinical trials [4], [5], [6]. And, since these trials delivered promising results, there is now a growing appreciation that MTH is capable of improving the neurologic outcome after CA [7], [8], [9]. Currently, data on MTH have been derived from clinical trials conducted under tightly controlled or experimental conditions [10], [11]. In the clinical practice, though, the time interval between the occurrence of CA and ensuing resuscitative measures can vary immensely depending on arrest location and daytime. Thus, whereas the overall benefit of MTH is meanwhile substantiated, the impact of the time intervals between CA and MTH on the neurologic outcome has not yet received much attention.

We hypothesized that the clinical benefit of MTH is greater among those patients in whom effective MTH is more rapidly achieved. To test this hypothesis, we analyzed the association of the time intervals from CA to MTH (1: time to cooling, 2: time to target temperature of 33.0 °C [TTT], 3: time to coldest temperature [TCT]) and the neurologic outcome under consideration of clinically relevant confounders. We also examined the correlation between those time intervals and serum levels of neurone specific enolase (NSE), a biochemical marker of brain tissue damage. Body cooling was performed by use of a closed-loop endovascular system which has recently been shown to allow more rapid achievement and more precise control of MTH [12].

Section snippets

Methods

The HELIOS Clinics Schwerin are an academic, regional tertiary-care hospital serving an estimated population of about 500,000 citizens in the German federal state of Mecklenburg-West Pomerania as well as in parts of northwestern Brandenburg. The hospital has a total of 1400 acute-care beds. Tertiary critical-care services include an 11-bed medical ICU for adult patients with non-surgical conditions. The medical ICU is a separate unit staffed by physicians specialized in non-surgical

Results

The study enrolled 49 patients. Fourteen of the 21 patients with poor neurologic outcome died (median survival time: 6 days, 20 h [2 days, 5 h–12 days, 0 h]) after intensive care was withdrawn in agreement with the patient's families. The 7 others remained in a comatose or vegetative state (N = 6) or retained a severe cerebral disability (N = 1) after achieving normothermia.

Discussion

We observed that those patients resuscitated from CA who had lower starting T at the beginning of cooling therapy, who had lower T after 1 h cooling therapy and who reached their coldest T sooner tended to be those with better neurologic outcome. Moreover, we found a correlation between maximum NSE, as a quantitative marker of brain tissue damage, and TCT in which shorter TCT were associated with lower maximum NSE levels. Finally, in multivariate analyses, any hour delay till the coldest T or

Conclusion

According to our data, early achievement of MTH is a determinant of the final neurologic outcome. Thus, measures to speed up the initiation of cooling therapy after CA appear warranted.

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