Elsevier

Resuscitation

Volume 80, Issue 4, April 2009, Pages 418-424
Resuscitation

Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest,☆☆

https://doi.org/10.1016/j.resuscitation.2008.12.015Get rights and content

Abstract

Background

Comatose survivors of out-of-hospital cardiac arrest (OHCA) have high in-hospital mortality due to a complex pathophysiology that includes cardiovascular dysfunction, inflammation, coagulopathy, brain injury and persistence of the precipitating pathology. Therapeutic hypothermia (TH) is the only intervention that has been shown to improve outcomes in this patient population. Due to the similarities between the post-cardiac arrest state and severe sepsis, it has been postulated that early goal-directed hemodyamic optimization (EGDHO) combined with TH would improve outcome of comatose cardiac arrest survivors.

Objective

We examined the feasibility of establishing an integrated post-cardiac arrest resuscitation (PCAR) algorithm combining TH and EGDHO within 6 h of emergency department (ED) presentation.

Methods

In May, 2005 we began prospectively identifying comatose (Glasgow Motor Score < 6) survivors of OHCA treated with our PCAR protocol. The PCAR patients were compared to matched historic controls from a cardiac arrest database maintained at our institution.

Results

Between May, 2005 and January, 2008, 18/20 (90%) eligible patients were enrolled in the PCAR protocol. They were compared to historic controls from 2001 to 2005, during which time 18 patients met inclusion criteria for the PCAR protocol. Mean time from initiation of TH to target temperature (33 °C) was 2.8 h (range 0.8–23.2; SD = h); 78% (14/18) had interventions based upon EGDHO parameters; 72% (13/18) of patients achieved their EGDHO goals within 6 h of return of spontaneous circulation (ROSC). Mortality for historic controls who qualified for the PCAR protocol was 78% (14/18); mortality for those treated with the PCAR protocol was 50% (9/18) (p = 0.15).

Conclusions

In patients with ROSC after OHCA, EGDHO and TH can be implemented simultaneously.

Introduction

There are more than 300 000 cardiac arrests per year in the United States.1, 2 More than 250 000 of them die and many survivors have significant neurologic deficits. Therapeutic hypothermia currently represents the most efficacious treatment option to reduce neurologic injury and mortality in comatose patients who have ROSC after cardiac arrest.3, 4 It is unknown whether adjunctive therapies used in concert with TH further improve outcomes.5

Clinical and laboratory investigations support the concept that the immediate post-arrest period exhibits a number of similarities to the sepsis syndrome, with elevated serologic markers of global inflammation, endothelial dysfunction and microcirculatory hypoperfusion.6 Some investigators have referred to this pathophysiologic state as the “post-resuscitation syndrome”.7 Using early goal-directed therapy (EGDT), an early goal-directed hemodyamic optimization (EGDHO) strategy applied at the most proximal phase of critical illness, Rivers and colleagues reduced in-hospital mortality from 46.5% to 30.5% in patients with severe sepsis and septic shock.8 This resuscitation strategy was endorsed by the Surviving Sepsis Campaign and incorporated into its sepsis care bundles.9 Subsequent publications describing the feasibility of implementing EGDT along with other aspects of a sepsis care bundle have demonstrated similar mortality reductions.10, 11, 12, 13

Given the similarities between the inflammatory responses associated with septic shock and the post-resuscitation syndrome, it is plausible that EGDHO may result in similar survival benefits in patients with ROSC after cardiac arrest. A post-resuscitation care bundle may benefit post-arrest patients in a similar fashion as sepsis care bundles have benefited patients with severe sepsis and septic shock.14 In fact, several recent publications have addressed other aspects of post-resuscitation care in addition to TH, including early percutaneous coronary intervention (PCI), intra-aortic balloon pumps for treatment of cardiogenic shock, EGDHO strategies, glucose and ventilator management strategies, and evaluation for relative adrenal insufficiency.15, 16, 17, 18, 19, 20, 21

However, none of these implementation studies have examined a specifically defined hemodynamic optimization strategy implemented at the most proximal phase of the post-resuscitation syndrome. We sought to evaluate the feasibility of implementing a comprehensive EGDHO protocol during induction of TH in patients immediately after ROSC. Our protocol incorporates clearly defined resuscitation endpoints and mandates implementation of EGDHO simultaneous with induction of TH and continuation of hemodynamic monitoring throughout the period on therapeutic cooling. We hypothesized that hemodynamic optimization of key physiologic endpoints—mean arterial pressure (MAP), central venous pressure (CVP), and central venous oxygen saturation (ScvO2)–could be achieved within 6 h of ROSC while implementing TH.

Section snippets

Methods

In this study, we performed an analysis of a prospectively collected database of cardiac arrest patients with ROSC treated with a combination of TH and EGDHO.

Results

Between May, 2005 and January, 2008, 208 patients with OHCA presented to our ED; 132/208 (64%) were of presumed cardiac etiology. Non-cardiac etiologies included hemorrhagic shock, intracranial hemorrhage, and environmental hypothermia. Of the presumed cardiac etiology subgroup, 38/132 (29%) had ROSC, and 34/132 (26%) survived to hospital admission. Of those admitted, 20/34 (59%) met inclusion criteria for the PCAR protocol; 18/20 (90%) of these patients were recognized prospectively by the

Discussion

Our study demonstrates successful implementation of TH and EGDHO in a hospital employing a multi-disciplinary post-cardiac arrest resuscitation protocol. We found that 78% of patients required interventions based upon our treatment algorithm and that 72% of patients were able to achieve EGDHO goals within 6 h of ROSC. We demonstrated a 28% absolute reduction in mortality when compared with historic controls, though the study was underpowered for the results to reach statistical significance.

Limitations

This study was performed at a single, academic medical center with a dedicated research and clinical staff to assist in the identification, enrollment, and management of patients eligible for TH and post-arrest EGDHO and, therefore, these results may not be generalizable to other institutions with different infrastructures and available resources. In addition, while 18/20 (90.0%) of the patients who qualified for the protocol were enrolled, this still may have served as a selection bias;

Conclusions

Our study demonstrated that performance of EGDHO optimization combined with TH is feasible in comatose cardiac arrest survivors. Using an algorithmic protocol, both hemodynamic and temperature goals can be achieved in the majority of patients within 6 h of ED presentation. Future clinical trials are needed to determine if EGDHO combined with TH improves outcome compared to therapeutic hypothermia alone in comatose cardiac arrest survivors.

Conflict of interest

Data collection and research assistants involved in the protocol were supported by an unrestricted research grant from Gaymar Industries (Orchard Park, New York). Study sponsors did not participate in subject recruitment, data collection, analysis, or preparation of this manuscript and did not review the manuscript prior to its submission. Dr. Gaieski has received consulting fees and honoraria from Gaymar Industries; Dr. Goyal has received consulting fees from Gaymar Industries and honoraria

Acknowledgements

We would like to acknowledge the invaluable contributions of the following persons to the development and implementation of the PCAR protocol: Linda Hoke, RN, Gail Delfin, RN, Jennifer Barger, RN, Leighann Schmidt, RN, and Thomas Levins, RN. This work would not have been possible without the hard work, dedication, and commitment of the entire nursing staffs of the ED, CCU, and MICU. We are indebted to Fran Shofer, PhD, for her statistical analyses and contributions to the methodology of the

References (36)

  • R.E. Hoesch et al.

    Coma after global ischemic brain injury: pathophysiology and emerging therapies

    Crit Care Clin

    (2008)
  • A.E. Jones et al.

    Goal-directed hemodynamic optimization in the post-cardiac arrest syndrome: a systematic review

    Resuscitation

    (2008)
  • E.P. Rivers et al.

    Venous hyperoxia after cardiac arrest. Characterization of a defect in systemic oxygen utilization

    Chest

    (1992)
  • E.P. Rivers et al.

    The effect of the total cumulative epinephrine dose administered during human CPR on hemodynamic, oxygen transport, and utilization variables in the postresuscitation period

    Chest

    (1994)
  • L.B. Becker et al.

    Racial differences in the incidence of cardiac arrest and subsequent survival. The CPR Chicago Project

    N Engl J Med

    (1993)
  • S.A. Bernard et al.

    Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia

    N Engl J Med

    (2002)
  • Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after...
  • C.M. Spaulding et al.

    Immediate coronary angiography in survivors of out-of-hospital cardiac arrest

    N Engl J Med

    (1997)
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    A Spanish translated version of the summary of this article appears as Appendix in the final online version at doi:10.1016/j.resuscitation.2008.12.015.

    ☆☆

    This work has been supported by an unrestricted research grant from Gaymar Industries (Orchard Park, New York).

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