Elsevier

Resuscitation

Volume 128, July 2018, Pages 204-210
Resuscitation

Clinical paper
Comparison of two sedation regimens during targeted temperature management after cardiac arrest

https://doi.org/10.1016/j.resuscitation.2018.03.025Get rights and content

Abstract

Purpose

Although guidelines on post-resuscitation care recommend the use of short-acting agents for sedation during targeted temperature management (TTM) after cardiac arrest (CA), the potential advantages of this strategy have not been clinically demonstrated.

Methods

We compared two sedation regimens (propofol-remifentanil, period P2, vs midazolam-fentanyl, period P1) among comatose TTM-treated CA survivors. Management protocol, apart from sedation and neuromuscular blockers use, did not change between the two periods. Baseline severity was assessed with Cardiac-Arrest-Hospital-Prognosis (CAHP) score. Time to awakening was measured starting from discontinuation of sedation at the end of rewarming. Awakening was defined as delayed when it occurred after more than 48 h.

Results

460 patients (134 in P2, 326 in P1) were included. CAHP score did not significantly differ between P2 and P1 (P = 0.93). Sixty percent of patients awoke in both periods (81/134 vs. 194/326, P = 0.85). Median time to awakening was 2.5 (IQR 1–9) hours in P2 vs. 17 (IQR 7–60) hours in P1. Awakening was delayed in 6% of patients in P2 vs. 29% in P1 (p < 0.001). After adjustment, P2 was associated with significantly lower odds of delayed awakening (OR 0.08, 95% CI 0.03–0.2; P < 0.001). Patients in P2 had significantly more ventilator-free days (25 vs. 24 days; P = 0.007), and lower catecholamine-free days within day 28. Survival and favorable neurologic outcome at discharge did not differ across periods.

Conclusions

During TTM following resuscitation from CA, sedation with propofol-remifentanil was associated with significantly earlier awakening and more ventilator-free days as compared with midazolam-fentanyl.

Introduction

Among comatose patients transported to hospital after cardiac arrest (CA), severe brain injury is the main cause of mortality [[1], [2], [3]]. Targeted temperature management (TTM) at either 33 or 36 °C during the first 24 h after return of spontaneous circulation (ROSC) is recommended in order to reduce anoxic-ischemic brain injury [[4], [5]]. Whatever the targeted level of temperature, these patients need to be adequately sedated during TTM in order to prevent shivering and to allow adequate ventilation [6]. Unfortunately, sedation may delay neurological recovery [7] after TTM and, therefore, the timing of neurological evaluation [[7], [8]]. Reducing the duration of uncertainty by refining the sedation regimen is crucial to avoid an inadequate prolongation of life-sustaining treatments in patients with an irreversible postanoxic brain injury.

Although guidelines recommend using short-acting-drugs for sedation in patients resuscitated from CA, current practices are heterogeneous and recent studies reported a prevalent or exclusive use of long-acting-drugs (mostly midazolam and fentanyl) [[6], [9], [10], [11], [12]]. These sedation regimens are associated with a delayed awakening in up to 30% of patients with good neurological recovery [7]. To date only one study compared short and long acting sedative [13]. However the small sample size did not allow multivariate adjustment. Considering the paucity of data, we decided to perform a comparison of two regimens of sedation and analgesia (long-acting-drugs, i.e., midazolam-fentanyl versus short-acting-drugs, i.e., propofol-remifentanil) in patients treated with TTM after resuscitation from CA. Our hypothesis was that a sedation regimen with short-acting-drugs would be associated with a reduction in the proportion of patients with delayed awakening, as compared with long-acting-drugs.

Section snippets

Population

We performed a study using prospectively collected data from the Parisian-Region-Out-of-Hospital-Cardiac-Arrest-Registry, previously published [[1], [7], [14]]. We included patients remaining comatose (Glasgow-Coma-Scale (GCS) ≤ 8) after CA and admitted to the intensive care unit (ICU) of Cochin Hospital (Paris, France). Exclusion criteria were: death from post-resuscitation shock within the first 48 h after ROSC and before a reliable neurological examination could be made; neurological cause

Characteristics and sedation

326 patients were included during P1 and 134 patients during P2 (Fig. 1). Baseline characteristics of included patients are described in Table 1. The rate of bystander CPR was higher during P2 (73% vs. 57% respectively; P = 0.001).

Patients included during P2 were older (64 years vs. 59 years, P = 0.004), and had a higher rate of post-resuscitation shock (60% vs. 45%, P = 0.005) before enrolment as compared with patients from P1. The severity of patients, as per CAHP score, did not significantly

Discussion

In this pragmatic study, sedation with propofol-remifentanil compared with midazolam-fentanyl was associated with a significantly lower rate of delayed awakening and a shorter duration of ventilation in patients sedated for TTM after cardiac arrest. The use of these short-acting-drugs was associated with a longer duration of catecholamine infusion, without an increase in the incidence of organ dysfunction. Finally, the use of short-acting-drugs allowed an earlier prognostication.

In the setting

Conclusion

In our study, the use of short-acting-drugs for sedation during TTM after cardiac arrest was associated with an earlier awakening, and a shorter duration of mechanical ventilation. This sedation regimen could allow an earlier prognostication after cardiac arrest, without increasing the risk complications or mortality.

Conflict of interest statement

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Acknowledgments

We thank Nancy Kentish-Barnes for her help in preparing the manuscript.

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  • Cited by (0)

    A Spanish translated version of the abstract of this article appears as Appendix in the final online version at https://doi.org/10.1016/j.resuscitation.2018.03.025.

    1

    Both authors contributed equally.

    2

    Both last authors contributed equally.

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