Should adrenaline be routinely used by the resuscitation team if a patient suffers a cardiac arrest shortly after cardiac surgery?

Summary

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether adrenaline might be a useful addition to a protocol for the management of cardiac arrests for patients shortly after cardiac surgery. Altogether 889 papers were found using the reported search, of which 16 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. The quality and level of evidence was assessed using the International Liaison Committee on Resuscitation guideline recommendations. We conclude that the European Resuscitation Council and the American Heart Association both recommend 1 mg of adrenaline as soon as pulseless electrical activity or asystole is identified or after the second failed shock if the rhythm is VF/pulseless VT. However, they acknowledge that the evidence behind this recommendation is lacking and based entirely on animal studies which have as yet not been successfully replicated in human studies to show a benefit of survival to hospital discharge. They acknowledge that the current evidence is insufficient to support or refute the use of adrenaline in arrests and the International Liaison Committee on Resuscitation grade the recommendation to give adrenaline in cardiac arrests as ‘indeterminate’. Thus, in the particular situation of a patient who arrests shortly after cardiac surgery where the chance of restoring sinus rhythm either by defibrillation or by an emergency re-sternotomy is high, and where adrenaline could in this situation be highly dangerous once sinus rhythm is restored, we recommend that 1 mg of adrenaline forms no part of the resuscitation protocol for patients who arrest after cardiac surgery.

1. Introduction

A best evidence topic was constructed according to a structured protocol. This is fully described in the ICVTS [1]. The quality of each study was assessed using the International Liaison Committee on Resuscitation 2005 protocol [2].

2. Three-part question

In [patients who have arrested shortly after cardiac surgery] does [the routine administration of 1 mg of adrenaline] improve [survival]?

3. Clinical scenario

A 72-year-old patient suffers a cardiac arrest 1 h after triple coronary artery bypass graft. The rhythm is pulseless electrical activity (PEA). The nursing staff commence cardiac massage and follow the European Resuscitation Council guideline which is to give 1 mg of adrenaline immediately for pulseless electrical activity (PEA) or asystole. The surgeon is rapidly available and performs an emergency resternotomy within 3 min. On reopening there is a considerable gush of blood and a tamponade is relieved. Sinus rhythm returns but unfortunately the blood pressure rapidly rises to 250/150 due to the adrenaline, and several of the proximal graft anastomosis sutures cut through. After redoing both top-ends and oversewing the aortic and venous cannulation sites, you wonder what possible benefit adrenaline was in that arrest scenario.

4. Search strategy

Medline-1950 to Nov-2007 using OVID interface.

[adrenaline.mp OR epinephrine.mp OR exp Epinephrine/] AND [exp Resuscitation/OR resuscitation.mp OR exp Cardiopulmonary resuscitation/] AND [exp survival/OR survival.mp OR exp Patient discharge/OR discharge.mp].

Embase-1980 to Nov-2007 using the OVID interface. Search repeated replacing keywords epinephrine with adrenaline, patient discharge with hospital discharge, and cardiopulmonary resuscitation with resuscitation.

Cochrane DSR, ACP journal club and DARE searched using the term ‘Adrenaline’.

5. Search outcome

Three hundred and twenty-eight papers were found in MEDLINE, 499 in EMBASE and 62 in the Cochrane collection using the reported search. From these, 16 papers were identified that provided the best evidence to answer the question. These are presented in Table 1 .

6. Results

The 2005 European Resuscitation Council Guidelines (ERC [3]) and the American Heart Association guidelines [4] state that for patients suffering a cardiac arrest with PEA or asystole, 1 mg of adrenaline should be given as soon as intravascular access is achieved and for every 3–5 min or every other loop of the algorithm. For VF/VT, adrenaline should be given after the second failed shock. However, the ERC state that ‘despite the widespread use of adrenaline during resuscitation, and several studies involving vasopressin, there is no placebo controlled study that shows that the routine use of any vasopressor at any stage during human cardiac arrest increases survival to hospital discharge. Current evidence is insufficient to support or refute the routine use of any particular drug or sequence of drugs. Despite the lack of human data, the use of adrenaline is still recommended, based largely on animal data.’ The evidence that they base this recommendation on are the worksheets produced by Long and Paradis [5] and Wenzel [6]. Long concludes that adrenaline use is supported by recent animal studies but that no human studies compare it to placebo. Also, they note that it produces adverse consequences and also subsequent doses are less effective. They give the level of evidence for adrenaline for VF or PEA/asystole as ‘indeterminate’ which is defined as ‘minimal evidence available, results inconsistent and contradictory and results not compelling’

Cairns and Niemann [7] studied 14 dogs who had VF for 7.5 min prior to resuscitation attempts. Three dogs survived and adrenaline increased their coronary perfusion pressure (CPP) by 21±11 mmHg. However, in the remainder, adrenaline only increased the CPP by 3±2 mmHg. Also subsequent doses had minimal effect on CPP.

Klouche et al. [8] studied 20 rats using differing resuscitative drugs after VF. They found that adrenaline impaired post-resuscitation myocardial function more than vasopressin and a selective alpha-agonist, and this function was similar to saline-placebo controls. However, survival was superior with adrenaline than with controls.

Lindberg et al. [9] in 18 pigs who had a sternotomy and chest closure, and then VF, showed that while either adrenaline or noradrenaline increased CPP during the arrest up to 45 mmHg compared to only 7 mmHg for controls, it significantly impaired cardiac output and oxygen delivery after successful resuscitation.

Chen et al. [10], in 47 rabbits arrested after ET-tube clamping, found that adrenaline increased CPP from 4 to 38 mmHg whereas vasopressin failed to do this. Half the rabbits given adrenaline survived compared to 10% of the vasopressin group.

Ristagno et al. [11] showed significantly worse cerebral blood flows and oxygenation with adrenaline compared to vasopressin in 10 pigs after cardiac arrest.

Vandycke and Martens [12] performed a meta-analysis of five RCTs of high-dose adrenaline vs. standard dose adrenaline. They found a superior odds of return of spontaneous circulation but no difference to hospital admission and a poorer outcome to hospital discharge with higher doses of adrenaline. Biondi-Zoccai et al. [13] performed a meta-analysis of vasopressin vs. adrenaline, finding only two human studies but demonstrating superiority of vasopressin across 33 animal studies. Zhong and Dorian [14] performed a review of adrenaline and vasopressin in cardiac arrest stating that adrenaline had many adverse effects post-resuscitation including myocardial dysfunction, worsening arrhythmias and increased myocardial oxygen demand and that human studies in this area were urgently needed.

Holmberg et al. [15] in a survey of 11,000 patients in patient-care who had arrested out-of-hospital looked at risk factors for adverse survival. They found that adrenaline was a predictor of adverse outcome for asystolic and VF arrests. Behringer et al. [16] reported that in 178 patients who survived an out-of-hospital arrest that adrenaline cumulative dose was much higher in those patients with a poor neurological outcome. The best human study in this area compared vasopressin with adrenaline but had no placebo group. Wenzel et al. [17] randomized over 1000 patients who arrested out-of-hospital to vasopressin or adrenaline. There was no difference in VF arrests but asystole and combined vasopressin and adrenaline showed better survival to hospital admission.

Pytte et al. [18] was struck by the fact that the benefit of adrenaline seen in experimental studies had not translated into clinical studies and hypothesised that this may be due to the difference between clinical CPR and the CPR obtained in a laboratory by hydraulic-compression devices. They compared these types of CPR and found that while labCPR produced significant haemodynamic effects with adrenaline, no haemodynamic increases were seen with clinicalCPR. Also the peak adrenaline level took 2.5 min to achieve in the clinicalCPR group after a single administration.

7. Clinical bottom line

The European Resuscitation Council and the American Heart Association both recommend 1 mg of adrenaline as soon as pulseless electrical activity or asystole is identified or after the second failed shock if the rhythm is VF/pulseless VT. However, they acknowledge that the evidence behind this recommendation is lacking and based entirely on animal studies which have as yet not been successfully replicated in human studies and thus the evidence for this recommendation is ‘indeterminate’. Thus, in the particular situation of a patient who arrests shortly after cardiac surgery where the chance of restoring sinus rhythm either by defibrillation or by an emergency re-sternotomy is high, and where adrenaline could in this situation be highly dangerous once sinus rhythm is restored, we recommend that 1 mg of adrenaline forms no part of the resuscitation protocol for patients after cardiac surgery.

References