Low chance of survival among patients requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac arrest in Sweden

doi:10.1016/S0300-9572(02)00048-5

Resuscitation

Volume 54, Issue 1, July 2002, Pages 37-45

https://doi.org/10.1016/S0300-9572(02)00048-5 Get rights and content

Abstract

Aim: To relate the outcome of out-of-hospital cardiac arrest to whether medication with adrenaline (epinephrine) was given and whether patients were intubated. Patients: A national survey in Sweden between 1990–1995 among patients suffering out-of-hospital cardiac arrest and in whom resuscitation was attempted. Sixty per cent of ambulance organisations in Sweden participated. Design: Prospective evaluation. Survival was defined as survival 1 month after cardiac arrest. Results: In all, 14 065 patients were included in the evaluation. Of these, resuscitation was attempted in 10 966 cases. Among these adrenaline (epinephrine) was given in 42.4 and 47.5% were intubated. In an univariate analysis treatment with adrenaline (epinephrine) and intubation was associated with a lower survival when all patients were evaluated. In a multivariate analysis including age, sex, place of arrest, bystander-CPR, initial arrhythmia, arrest being witnessed and aetiology, treatment with adrenaline (epinephrine) (OR 0.43, CI 0.27–0.66) and intubation (OR 0.71, CI 0.51–0.99) were both independent predictors of a lower chance of survival. When separately analysing patients with bystander witnessed cardiac arrest found in ventricular fibrillation and requiring more than 3 defibrillatory shocks neither treatment with adrenaline (epinephrine) nor intubation was associated with survival. Among patients with a non-shockable rhythm treatment with adrenaline (epinephrine) was a significant independent predictor for lower survival (OR 0.30, CI 0.07–0.82). Conclusion: In a national survey in Sweden including 10 966 cases of out-of-hospital cardiac arrest the outcome was related to whether medication with adrenaline (epinephrine) was given and whether patients were intubated. Neither in total nor in any subgroup did we find results indicating beneficial effects of any of these two interventions. Whether treatment with adrenaline (epinephrine) or intubation will increase survival after out-of-hospital cardiac arrest needs to be confirmed in prospective randomised trials.

Introduction

Although, adrenaline (epinephrine) and tracheal intubation are recommended as treatment by the American Heart Association (AHA) and the European Resuscitation Council (ERC) at cardiac arrest (CA) there are no studies supporting their positive effect on survival in humans [1], [2]. This lack of information has implications for planning and maintenance of EMS systems around the world.

Most of the patients with heart disease and cardiac arrest suffer from initial ventricular fibrillation (VF) as shown in prospective, non-randomised trials and observational studies that early defibrillation could save a large proportion of these patients and that early CPR further increases survival [3].

In the current algorithm from the ERC and AHA both adrenaline (epinephrine) and intubation are recommended in every prolonged resuscitative procedure both for patients in VF and for patients with non-VF. Patients in cardiac arrest who require prolonged, complex treatment have a very poor prognosis and have low survival rates associated with neurological deficits. It has been hard to find support for improved survival with adrenaline (epinephrine) and intubation in these patient groups in prospective, non-randomised trials as this would require large numbers of patients. Randomised-controlled trials have also been difficult to perform on ethical grounds.

The recommendations from ERC and AHA have organisational and economic implications as both intubation and medication requires a complicated and costly training and control system. If these interventions are without effect on survival, they should be removed from the recommendations of standard treatment of cardiac arrest. This should simplify training programmes and allow the ambulance staff to concentrate on the treatments known to increase survival.

In Sweden since 1990 there is an ongoing national registry of out-of-hospital cardiac arrests where patients from all over Sweden are included. The emergency medical systems have variable proficiency and means of resuscitation. These differences have led to a registry where it was possible to analyse the association between the use of adrenaline (epinephrine) and intubation and survival.

The aim of this study was to investigate (a) the proportion of patients with out-of-hospital cardiac arrest who were given adrenaline (epinephrine) and intubation (b) the association between the use of adrenaline (epinephrine) and intubation and survival.

Section snippets

Statistical methods

All analyses were performed using statistical analysis system. Pitman's non-parametric test was used. In evaluations of dichotomous variables Fisher's exact test, a special form of Pitman's test was used. A P-value of less than 0.05 was regarded as significant. Two-tailed tests were applied. For multivariate analysis, a stepwise logistic regression procedure was used.

Ambulance registry

This study was based on material collected within the Swedish ambulance cardiac arrest registry. The registry started in 1990

Results

Between January 1990 and May 1995 14 065 reports on cardiac arrest were collected. Resuscitation was attempted in 10 966 cases. In the remaining 3099 cases no resuscitation was attempted and the patient was transported to hospital only to be declared dead.

In 60.2% of the patients the cardiac arrest was witnessed by bystanders and in 9.9% by ambulance crew. In 29.9% cases the arrest was unwitnessed. In 43.3% of the patients the presenting ECG showed a shockable rhythm and in 56.7% a

Discussion

Adrenaline (epinephrine) and intubation have been included in the AHA algorithm of resuscitation since 1974 and when AHA reintroduced the concept of ‘chain of survival’ in 1991 there was consensus on the positive effect of the three first links of the chain namely early access, early CPR and early defibrillation, where positive effects on survival has been demonstrated in numerous non-randomised prospective and observational studies. The fourth link (early ACLS, i.e. drugs and intubation) in

Limitations of the study

Our study has severe limitations and the data must be interpreted with caution. In contrast to a randomised trial we cannot assume that the patient groups with and without treatment with adrenaline (epinephrine) and intubation are comparable. In fact, it is demonstrated that for the total patient group there are significant differences in a number of variables between those with and without treatment with adrenaline (epinephrine) and intubation.

Even for the most well defined group in our study,

Conclusion

In our prospective observational study we have not found any data indicating a positive effect of adrenaline (epinephrine) or intubation on survival. Randomised-controlled studies are needed.

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Cited by (123)

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A growing number out-of-hospital cardiac arrest (OHCA) registries have been developed across the globe. A few of these are national, while others cover larger geographical regions. These registries have common objectives; continuous quality improvement, epidemiological research and providing infrastructure for clinical trials. OHCA registries make performance comparison across Emergency Medical Services systems possible for benchmarking, hypothesis generation and further research. Changes in OHCA incidence and outcomes provide insights about the effects of secular trends or health services interventions. These registries, therefore, have become a mainstay of OHCA management and research. However, developing and maintaining these registries is challenging. Coordination of different service providers to support data collection, sustainable resourcing, data quality and data security are the key challenges faced by these registries.
Despite all these challenges, noteworthy progress has been made and further standardization and co-ordination across registries can result in great international benefit. In this paper we present a ‘why’ and ‘how to’ model for setting up OHCA registries, and suggestions for better international co-ordination through a Global OHCA Registries Collaborative (GOHCAR). We draw together the knowledge of a cohort of international researchers, with experience and expertise in OHCA registry development, management, and data synthesis.
Characteristics and outcome after out-of-hospital cardiac arrest with the emphasis on workplaces: an observational study from the Swedish Registry of Cardiopulmonary Resuscitation
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Characteristics and outcome in out-of-hospital cardiac arrest (OHCA) occurring at workplaces is sparsely studied.
To describe (1) the characteristics and 30-day survival of OHCAs occurring at workplaces in comparison to OHCAs at other places and (2) factors associated with survival after OHCAs at workplaces.
Data on OHCAs were obtained from the Swedish Registry of Cardiopulmonary Resuscitation from 1 January 2008 to 31 December 2018. Characteristics and factors associated with survival were analysed with emphasis on the location of OHCAs.
Among 47,685 OHCAs, 529 cases (1%) occurred at workplaces. Overall, in the fully adjusted model, all locations of OHCA, with the exception of crowded public places, displayed significantly lower probability of survival than workplaces. Exhibiting a shockable rhythm was the strongest predictor of survival among patients with OHCAs at workplaces; odds ratio (95% CI) 5.80 (2.92–12.31). Odds ratio for survival for women was 2.08 (95% CI 1.07–4.03), compared with men. At workplaces other than private offices, odds ratio for survival was 0.41 (95% CI 0.16–0.95) for cases who did not receive bystander CPR, as compared to those who did receive CPR. Among patients who were found in a shockable rhythm were 23% defibrillated before arrival of ambulance, which was more frequent than in any other location.
Out-of-hospital cardiac arrest occurring at workplaces and crowded public places display the highest probability of survival, as compared with other places outside hospital. An initial shockable cardiac rhythm was the strongest predictor of survival for OHCA at workplaces.
A Time-Dependent Propensity Score Matching Approach to Assess Epinephrine Use on Patients Survival Within Out-of-Hospital Cardiac Arrest Care
2020, Journal of Emergency Medicine
Citation Excerpt :
Regarding survival, in both groups with nonshockable rhythms or with shockable rhythms, we observed that epinephrine use was associated with a decrease in D30 survival compared with controls. Some other studies have also highlighted negative impacts of epinephrine on D30 survival, and others did not (7,9,12,13,15,30). However, previous findings did not support robust conclusions regarding the efficacy of epinephrine due to methodological issues or conflicting results (10,11,13–15).
Epinephrine effectiveness and safety are still questioned. It is well known that the effect of epinephrine varies depending on patients’ rhythm and time to injection.
We aimed to assess the association between epinephrine use during out-of-hospital cardiac arrest (OHCA) care and patient 30-day (D30) survival.
Between 2011 and 2017, 27,008 OHCA patients were included from the French OHCA registry. We adjusted populations using a time-dependent propensity score matching. Analyses were stratified according to patient's first rhythm. After matching, 2837 pairs of patients with a shockable rhythm were created and 20,950 with a nonshockable rhythm.
Whatever the patient's rhythm (shockable or nonshockable), epinephrine use was associated with less D30 survival (odds ratio [OR] 0.508; 95% confidence interval [CI] 0.440–0.586] and OR 0.645; 95% CI 0.549–0.759, respectively). In shockable rhythms, on all outcomes, epinephrine use was deleterious. In nonshockable rhythms, no difference was observed regarding return of spontaneous circulation and survival at hospital admission. However, epinephrine use was associated with worse neurological prognosis (OR 0.646; 95% CI 0.549–0.759).
In shockable and nonshockable rhythms, epinephrine does not seem to have any benefit on D30 survival. These results underscore the need to perform further studies to define the optimal conditions for using epinephrine in patients with OHCA.
Frequency of Medical Reversal Among Published Randomized Controlled Trials Assessing Cardiopulmonary Resuscitation (CPR)
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To characterize what proportion of all randomized controlled trials (RCTs) among patients experiencing cardiac arrest find that an established practice is ineffective or harmful, that is, a medical reversal.
We reviewed a database of all published RCTs of cardiac arrest patient populations between 1995 and 2014. Articles were classified on the basis of whether they tested a new or existing therapy and whether results were positive or negative. A reversal was defined as a negative RCT of an established practice. Further review and categorization were performed to confirm that reversals were supported by subsequent systematic review, as well as to identify the type of medical practice studied in each reversal. This study was conducted from October 2017 to June 17, 2019.
We reviewed 92 original articles, 76 of which could be conclusively categorized. Of these, 18 (24%) articles examined a new medical practice, whereas 58 (76%) tested an established practice. A total of 18 (24%) studies had positive findings, whereas 58 (76%) reached a negative conclusion. Of the 58 articles testing existing standard of care, 44 (76%) reversed that practice, whereas 14 (24%) reaffirmed it.
Reversal of cardiopulmonary resuscitation practices is widespread. This investigation sheds new light on low-value practices and patterns of medical research and suggests that novel resuscitation practices have low pretest probability and should be empirically tested with rigorous trials before implementation.
Adrenaline, ROSC and survival in patients resuscitated from in-hospital cardiac arrest
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To describe how administration of adrenaline is associated with return of spontaneous circulation (ROSC) and 30-day survival in patients with in-hospital cardiac arrest (IHCA).
Retrospective observational study.
Analysis of data extracted from a national cardiac arrest registry.
Patients >18 years old with IHCA from January 2015 up to June 2017.
Primary outcomes were ROSC and 30-day survival. Secondary outcome was survival to hospital discharge with a good neurologic outcome defined as cerebral performance category (CPC) score 1–2.
Of 6033 patients eligible for inclusion, 4055 (67%) received at least one dose of adrenaline. The rate of ROSC was lower in the adrenaline group (72 vs. 98% for shockable rhythm and 50% versus 65% for non-shockable rhythm; p < 0.0001 for both). Patients who had been treated with adrenaline showed a lower rate of 30-day survival (30 vs. 85% for shockable rhythm and 12 vs. 48% for non-shockable rhythm; p < 0.0001 for both). Survival to hospital discharge with a good neurological outcome was lower in the adrenaline group (22 vs. 80% for shockable rhythm and 8 vs. 41% for non-shockable rhythm; p < 0.0001 for both). There was a marked imbalance between the two groups in median duration of cardiopulmonary resuscitation. Stratification by duration of cardiopulmonary resuscitation attenuated the differences in outcomes between treatment groups and in patients with an initial non-shockable rhythm the association between adrenaline and ROSC was reversed to the benefit for adrenaline.
In our cohort of 6033 patients retrieved from a national cardiopulmonary resuscitation registry, administration of adrenaline during resuscitation from IHCA was associated with a lower rate of ROSC and 30-day survival.
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2019, Resuscitation
To systematically review the literature on advanced airway management during adult cardiac arrest in order to inform the International Liaison Committee of Resuscitation (ILCOR) consensus on science and treatment recommendations.
The review was performed according to PRISMA guidelines and registered on PROSPERO (CRD42018115556). We searched Medline, Embase, and Evidence-Based Medicine Reviews for controlled trials and observational studies published before October 30, 2018. The population included adult patients with cardiac arrest. Two investigators reviewed studies for relevance, extracted data, and assessed the risk of bias of individual studies.
We included 78 observational studies and 11 controlled trials. Most of the observational studies and all of the controlled trials only included patients with out-of-hospital cardiac arrest. The risk of bias for individual observational studies was overall assessed as critical or serious, with confounding and selection bias being the primary sources of bias. Three of the controlled trials, all published in 2018, were powered for clinical outcomes with two comparing a supraglottic airway to tracheal intubation and one comparing bag-mask ventilation to tracheal intubation. All three trials had some concerns regarding risk of bias primarily due to lack of blinding and variable adherence to the protocol. Clinical and methodological heterogeneity across studies, for both the observational studies and the controlled trials, precluded any meaningful meta-analyses.
We identified a large number of studies related to advanced airway management in adult cardiac arrest. Three recently published, large randomized trials in out-of-hospital cardiac arrest will help to inform future guidelines. Trials of advanced airway management during in-hospital cardiac arrest are lacking.

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Portuguese Abstract and Keywords
Objectivo: Relatar o resultado da paragem cardı́aca extra-hospitalar quando foi administrada adrenalina (epinefrina) e os doentes foram intubação. Doentes: Uma pesquisa nacional na Suécia entre 1990-1995 em doentes que sofreram paragem cardı́aca extra-hospitalar e em quem foi tentada a reanimação. Participaram sessenta por cento das organizações de ambulâncias da Suécia. Método: Avaliação prospectiva. Sobrevida foi definido como sobrevivência 1 mês após a paragem cardı́aca. Resultados: No total, foram incluı́dos no estudo 14065 doentes. Destes, a reanimação foi tentada em 10966. Adrenalina (epinefrina) foi administrada em 42.4% e 47.5% foram intubados. Numa análise univariada o tratamento com adrenalina (epinefrina) e intubação estava associado com menor sobrevida quando todos os doentes eram avaliados. Numa análise multivariada, incluindo idade, sexo, local da paragem, reanimação por transeunte, arritmia inicial, paragem testemunhada e etiologia, o tratamento com adrenalina (epinefrina) (OR 0.43, CI 0.27–0.66) e a intubação (OR 0.71, CI 0.51–0.99) eram ambos factores predictivos independentes de menor probabilidade de sobrevida. Quando se analisava separadamente doentes com paragem cardı́aca testemunhada em fibrilhação ventricular e que necessitaram de mais de três choques, nem o tratamento com adrenalina (epinefrina) nem a intubação estavam associadas com sobrevida. Entre os doentes com ritmo não desfibrilável, o tratamento com adrenalina (epinefrina) era um factor predictivo significativo para menor sobrevida (OR 0.30, CI 0.07–0.82). Conclusão: Num estudo nacional na Suécia que incluiu 10966 casos de paragem cardı́aca extra-hospitalar, o prognóstico estava relacionado a administração de adrenalina (epinefrina) e com a intubação dos doentes. Não encontramos resultados indicadores de um efeito benéfico de nenhuma destas atitudes no grupo do total dos doentes ou em qualquer subgrupo considerado. Se o tratamento com adrenalina (epinefrina) ou intubação irá aumentar a sobrevida após paragem cardı́aca extra-hospitalar precisa de ser confirmado em estudos prospectivos randomizados.
Palavras chave: Adrenalina; Fibrilação ventricular; Paragem cardı́aca
Spanish Abstract and Keywords
Objetivo: Relacionar el resultado del paro cardı́aco prehospitalario con el uso del medicamento adrenalina (epinefrina) y con la intubación de los pacientes. Pacientes: Encuesta nacional en suecia entre 1990–1995 entre los pacientes que sufrieron un paro cardı́aco extrahospitalario en quienes se intentó resucitación. Participaron 60% de las organizaciones de ambulancias de Suecia. Diseño: Evaluación prospectiva. Se definió sobrevida como sobrevida un mes después del paro cardı́aco. Resultados: Se incluyeron en total 14065 pacientes en la evaluación. De estos , se intentó la tesucitación en 10966 casos. Entre estos se usó adrenalina en el 42.4 % y fueron intubados en la tráquea un 47.5%. En un análisis unidireccional del tratamiento con adrenalina (epinefrina) e intubación estos tratamientos se asociaron con menor sobrevida cuando se evaluaban todos los pacientes. En un analisis multivariable que incluye edad, sexo, lugar del paro cardı́aco, presencia de reanimación por testigos, arritmias iniciales, paro presenciado y etiologı́a, tratamiento con adrenalina(epinefrina) (OR 0.43, CI 0.27–0.66) y con intubación (OR 0.71, CI 0.51–0.99) siendo ambos predictores independientes de una baja peobabilidades de sobrevida. Cuando se analiza separadamente los pacientes con paro presenciado encontrados en fibrilación ventricular que requirieron mas de tres descargas desfibriladoras no se asoció ni la sobrevida con tratamiento con adrenalina (epinefrina) ni con intubación traqueal. Entre los pacientes con ritmo inicial no desfibrilable el tratamiento con adrenalina (epinefrina) fue un factor de prediccion para baja sobrevida (OR 0.30, CI 0.07–8.82). Conclusión: En una encuesta nacional en suecia, que incluı́a 10966 casos de paro cardı́aco prehospitalario se relacionó con el curso. No encontramos resultados que mostraran beneficios de cualquiera de estas 2 intervenciones. Si acaso el tratamiento con adrenalina (epinefrina) o la intubación traquel mejoran la sobrevida después de un paro cardı́aco pre hospitalario deberá ser confirmado con estudio prospectivo randomizado.
Palabras clave: Adrenalina; Fibrilación ventricular; Paro cardı́aco

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Low chance of survival among patients requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac arrest in Sweden

Abstract

Introduction

Section snippets

Statistical methods

Ambulance registry

Results

Discussion

Limitations of the study

Conclusion

Ann. Emerg. Med.

Ann. Emerg. Med.

Resuscitation

Resuscitation

J. Emerg. Med.

Improving survival from sudden cardiac arrest: the ‘chain of survival’ concept

Circulation

The role of epinephrine in cardiac resuscitstion

Anesth. Analg.