Elsevier

Resuscitation

Volume 83, Issue 3, March 2012, Pages 347-352
Resuscitation

Clinical paper
Randomised study of hypertonic saline infusion during resuscitation from out-of-hospital cardiac arrest

https://doi.org/10.1016/j.resuscitation.2011.09.005Get rights and content

Abstract

Aim of the study

Animal models of hypertonic saline infusion during cardiopulmonary resuscitation (CPR) improve survival, as well as myocardial and cerebral perfusion during CPR. We studied the effect of hypertonic saline infusion during CPR (Guidelines 2000) on survival to hospital admission and hospital discharge, and neurological outcome on hospital discharge.

Methods

The study was performed by the EMS of Bonn, Germany, with ethical committee approval. Study inclusion criteria were non-traumatic out-of-hospital cardiac arrest, aged 18–80 years, and given of adrenaline (epinephrine) during CPR. Patients were randomly infused 2 ml kg−1 HHS (7.2% NaCl with 6% hydroxyethyl starch 200,000/0.5 [HES]) or HES over 10 min.

Results

203 patients were randomised between May 2001 and June 2004. After HHS infusion, plasma sodium concentration increased significantly to 162 ± 36 mmol l−1 at 10 min after infusion and decreased to near normal (144 ± 6 mmol l−1) at hospital admission. Survival to hospital admission and hospital discharge was similar in both groups (50/100 HHS vs. 49/103 HES for hospital admission, 23/100 HHS vs. 22/103 HES for hospital discharge). There was a small improvement in neurological outcome in survivors on discharge (cerebral performance category 1 or 2) in the HHS group compared to the HES group (13/100 HHS vs. 5/100 HES, p < 0.05, odds-ratio 2.9, 95% confidence interval 1.004–8.5).

Conclusion

Hypertonic saline infusion during CPR using Guidelines 2000 did not improve survival to hospital admission or hospital discharge. There was a small improvement with hypertonic saline in the secondary endpoint of neurological outcome on discharge in survivors. Further adequately powered studies using current guidelines are needed.

Introduction

Fluid infusion during CPR is not specifically recommended in both 2005 and 2010 CPR guidelines.1, 2

Whereas infusion of cooled fluids after return of a spontaneous circulation (ROSC) has been investigated in several studies as a method to induce therapeutic hypothermia,3, 4, 5 there are few studies on which fluid and the amount of fluid to infuse during CPR.6 However, it is well known, that pathophysiological changes such as haemoconcentration,7, 8, 9 endothelial cell swelling and rolling,10 and sticking of leucocytes11 also compromise myocardial and cerebral capillary reperfusion. Several experimental studies after cardiac arrest and CPR demonstrated haemoconcentration due to capillary leakage and plasma loss of up to 20 ml kg−1.7, 8, 9 One therapeutic option to compensate this plasma loss could be the infusion of a large volume of an isotonic solution. This approach, however, will not reverse endothelial cell swelling and microvascular disturbances and has been shown to decrease cerebral and myocardial perfusion pressure during CPR in animal models.12, 13, 14

An option to increase blood volume and to improve hemodynamics as well as organ blood flow under conditions of haemorrhagic shock and brain trauma is the infusion of a small volume of a hypertonic solution (“small volume resuscitation”).15, 16, 17, 18, 19, 20 In the last 15 years the use of hypertonic solutions during CPR has been systematically investigated in several experimental studies.21, 22, 23, 24, 25 The rationale to test this therapeutic option during CPR were the known effects of hypertonic solutions from haemorrhagic shock models, i.e. the increase in intravascular volume, and a decrease in ischaemic endothelial cell swelling and leukocyte activation. In experimental cardiac arrest/CPR models the use of hypertonic saline significantly increased myocardial blood flow, myocardial perfusion pressure, and cardiac index during CPR.21, 25 In addition, microcirculatory reperfusion of the brain was improved, cerebral no-reflow phenomenon was reduced and blood flow during CPR was sustained or even improved in hypertonic saline hydroxyethyl starch treated animals.22, 24 In these experimental studies infusion of hypertonic solution significantly increased resuscitation success and survival rate.21, 22, 24 Furthermore, Krieter et al. found that hypertonic saline application after resuscitation from cardiac arrest reduced astroglial S-100β protein release, which might indicate a possible reduction of neuronal injury after CPR.26 In addition Noppens et al. found improved long term outcome and neurological recovery after an early bolus of hypertonic saline hydroxyethyl starch after global cerebral ischaemia.27

In the treatment of haemorrhagic shock a dosage of 4 ml kg−1 bodyweight is recommended. After cardiac arrest similar effects on myocardial reperfusion and success rate were found after infusion of 2 or 4 ml kg−1 hypertonic saline within 10 or 20 min.22, 24

In the current study after initial enrolment of 66 patients a planned interim analysis showed the feasibility and safety of an intravenous infusion of hypertonic saline/hydroxyethyl starch (HHS) during CPR after out-of-hospital cardiac arrest.28 The study was therefore continued with a plan to enroll 200 patients to investigate survival to hospital admission as primary endpoint, and survival to hospital discharge and neurological outcome at hospital discharge as secondary endpoints.

Section snippets

Methods

The study was conducted by the Department of Anaesthesiology and Intensive Care Medicine of the University Hospital Bonn, Germany. It was performed in accordance with the declaration of Helsinki and in accordance with all current German regulations and standards for investigations upon human subjects after approval of the local ethical committee (December 11th 2000, Ethical board at the medical faculty of the University of Bonn, approval number 245/00). Informed consent of patients or relatives

Patients

Between May 2001 and June 2004, a total of 337 patients were resuscitated in the EMS of Bonn, Germany. One hundred and nine patients were not randomised, and subsequently 19 patients were excluded. Thus a total of 203 patients were included in the analysis, 103 patients received an infusion of HES during CPR and 100 patients received an infusion of HHS (Fig. 1). The two groups were similar in terms of demographics, timing of the collapse and the resuscitation measures needed, and the

Discussion

Infusion of hypertonic saline during CPR did not improve survival to hospital admission or hospital discharge in our study. but it improved the neurological outcome of patients alive compared with the control group or other clinical trials.32 However, as the study was not powered to examine neurological outcome, the findings in neurological improvement have limited validity.

Conclusions

Hypertonic saline infusion during CPR using Guidelines 2000 did not improve survival to hospital admission or hospital discharge. There was a small improvement with hypertonic saline in the secondary endpoint of neurological outcome on discharge in survivors.

The validity of our findings is limited, because the study used 2000 CPR guidelines, and was too small to study neurological recovery as primary endpoint.

This study does show that a new multi-centre study using 2010 CPR guidelines that is

Conflict of interest statement

Martin Breil, Henning Krep, Ulli Heister, Andreas Bartsch, Raphael Bender, Bernadette Schaefers and Andreas Hoeft declare to have no conflicts of interest. Matthias Fischer received lecture fees from Fresenius SE & Co. KGaA in the years 1998–2003. This study was investigator driven, but Fresenius SE & Co. KGaA prepared and donated the study drugs in identically infusion bags. Fresenius SE & KGaA was not involved in data analyses, interpretation of results or conduct of the study.

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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.2011.09.005.

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    These authors contributed equal to this study.

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