Clinical Trials on Cardiac Arrest

Efficacy of Adrenaline in Out-of-Hospital Cardiac Arrest

Levels of evidence

Audience

Search Strategy

Inclusion Criteria

Exclusion Criteria

Prior Research

Issues with Prior Studies

Efficacy of Adrenaline in Out-of-hospital Cardiac Arrest

Levels of evidence

Observational studies

Randomized control trials

Randomized clinical blinded trial

Retrospective studies

Audience

This objective of this paper was to find out whether adrenaline is efficient in out-of-hospital patient. Therefore, information here within can be of help to investigators on the same, students and any other reader. The study uses simple English, which makes it understandable to a wide variety of readers.

Search Strategy

For this study, the electronic databases including Pub Med, EmBase, Medline, Cochrane, and Google Scholar were searched to identify relevant literature. The study used some search terms for the strategy such as, "efficacy of adrenaline, effectiveness of norepinephrine and the effectiveness of vasopressor" and "heart arrest, cardiac arrest and therapy," "cardiopulmonary resuscitation, cerebral resuscitation" to retrieve relevant literature.

Inclusion Criteria

In this study, the identified studies were those of empirical studies. Even though it is not possible to conduct studies, which are free of limitations, the study included studies that followed research designs that could lead to empirical data. In addition, studies, which coincided with the following criteria, for example, human studies, controlled trials, meta-analyses and case studies.

Exclusion Criteria

Consequently, studies were excluded when the study failed to have an abstract, if the abstract existed, but it had no study, the reference was a non-English abstract, the investigation in the study was an animal trial, the study was a case report, the study was a literature review and the vasopressor was used in the treatment of traumatic cardiac arrest.

Abstract

Background:

There is evidence that has shown adrenaline was a historical drug. Currently, it is still in use for the same purpose as before; in cardiac arrest patients. However, despite this usage since 1896, there is still no enough evidence on its influence on out-of-hospital cardiac arrest patients. Therefore, this study aims to address whether adrenaline is effective, and the information relies greatly on a number of prior studies.

Methods:

For this study, information was retrieved from relevant paper through a search on Pub Med, EmBase, Medline, Cochrane and the Google Scholar. Terms including "efficacy of adrenaline, effectiveness of norepinephrine and the effectiveness of vasopressor" and "heart arrest, cardiac arrest and therapy," "cardiopulmonary resuscitation, cerebral resuscitation" were central in this study.

Results:

The search yielded a mixture of studies, ranging from cohort, randomized clinical trials, observational and they showed similar results in terms of improved short-term outcomes, and circulation, but mixed results on the efficacy of adrenaline in out-of-hospital in cardiac arrest patients.

Conclusion:

From the literature, it was evident that cardiac arrest is a significant health problem in the globe. In addition, there are a number of studies reporting on the use of adrenaline in out-of-hospital patients, but the mixed results on the same has raised concerns and scrutiny of the methodologies employed by the investigators. However, results are consistent and there is inadequate evidence to support the efficacy of adrenaline. Nonetheless, there is room for future research to ascertain the same.

Introduction

Cardiac arrest is a global medical issue with very poor prognosis. For example, in United States, studies report that the incidences of cardiac arrest ranges from 165,000 to 450,000 in a year. In the same context, survival to hospital discharge in events of pre-hospital cardiac arrests is around 5-8% in the United States, and in the globe, the survival rate is less than 1%. Moreover, in-hospital arrest, the incidences of survival are better because they are around 12%. Nonetheless, the overall survival incidents for both in and out of hospital remain poor (1). In addition, survival without adverse neurological impairment is still low, and has not improved over the past few decades.

Conversely, adrenalines has been widely utilized in cardiac arrest for more than ten decades, but have attracted diverse controversies, mainly because of their association with negative effects (2). The controversies are further widening in scope because there is evidence, which supports that adrenaline can be a potential promising alternative vasopressor to use in case of cardiac arrest. In this regard, there are substantial clinical trials, which have demonstrated that the adrenaline has improved survival rates. Until recently, the promising advantages of the drug have attracted attention from investigators. Some human studies have also shown improved survival rates after patients used the drug for cardiac arrest.

What even calls for further research is the emerging evidence, which suggests that the use of adrenaline in cardiac arrest has shown poor neurologic and survival rate. The evidence shows that the drug has associations with adverse alterations in cerebral perfusion, microculation and myocardial function post-arrest. Therefore, although there is a large body of research concerning the topic, it is apparent that there is no conclusive evidence about the effectiveness of adrenaline in patients with out of hospital cardiac arrest (5, 8). On the other hand, it is not clear if pre-hospital use of adrenaline has benefits in long-term prognoses, which remains inconclusive; however, the use of adrenaline is effective in terms of returning spontaneous circulation.

In comparison, randomized control trials have suggested that pre-hospital adrenaline improves survival rates, whereas observational studies have suggested the exact opposite. The contradictory outcomes from studies may be due to methodological flaws (15). In this context, the randomized trials may be underpowered, whereas the observational studies may not have been capable of adjusting in time dependent imbalance (20). A few studies, on the other hand, have focused on timing, and then shown that timing in the administration of adrenaline could influence the outcomes. Prior studies ignored the potential use of adrenaline in the hospital and without such data, assessing of the pharmacological influence of adrenaline becomes unachievable.

Prior Research

Apparently, most of the early studies, which assessed the effect of adrenaline in the adult out-of-hospital cardiac arrest, were primarily observational studies. The studies often examined the variations in ROSC, survival rates and neurological outcomes amid OHCA patients treated through administration of adrenaline, and patients treated without adrenaline, within the same study (3). A particular study showed that there was a link between decreased survival rates when in case of adrenaline administration. There was another category of observational studies that aimed to show modifications in cardiac arrest guidelines to make it possible for administration of adrenaline (4). This was in Japan, where administration of adrenaline was only permissible for the patients who physicians attended to by a physician-manned ambulance.

The adrenaline treated cohort of 15030 patients was then put in comparison with patients not treated with adrenaline. In the results, it is clear that there was a one month reduction of survival rates in the patients who went through treatment by administration of adrenaline (4). However, there were cases of poor effects in the context of neurological results, particularly in cerebral performance, but there was improved ROSC for the group treated with adrenaline. In another study conducted in Singapore to examine the effects of treating patients with adrenaline, the study did not find any significant variations between the treated and untreated group of patients (5).

Another observational study in Japan, which aimed to compare regions where emergency departments involved manning (where there was no administration of adrenaline), and where the physician manned emergency departments, and in this case, they could administer adrenaline. Similarly, there was no significant difference noted in the two studies (6). Evidence shows that there is an association between adrenaline and increased ROSC. In this regard, the clinical significance of this result is inconclusive with several studies reporting either no improvement or a reduction in survival rates to hospital discharge, or a reduction in significant neurological results (4).

In a randomized trials of adrenaline in relation to cardiac arrest, the study illustrated that adrenaline resulted to an increase in ROSC, but not in the outcomes of survival rates to hospital discharge. The findings are in line with the observational and non-randomized trials; however, there is a need for randomized trials in humans to allow for direct comparison and generalization (7). In an intravenous drug administration in comparison to no such intervention during cardiac arrest, prior studies suggest that there were many patients who achieved ROSC and a non-significant increase in the survival rates of hospital discharge (8).

In a particular randomized study, this specifically aimed to investigate the survival outcomes in HDE vs. SDE vs. placebo in all the patients, who presented in either asystole or VF arrest. In the study design, investigators conducted randomized trials, and blinded patients to receive HDE (10 mg) or placebo (saline) in the first 5-10 minutes of cardiac arrest, followed by 1 mg doses of adrenaline in accordance to the ACLS requirements at the time. The findings, however, showed results, which were consistent with prior studies. The authors showed that there was no difference in the survival rates, including hospital discharge between any of the groups.

In another retrospective study, this aimed at examining patients with VF arrest who did not receive adrenaline during cardiac arrest. The results show that patients who sustained VF and treated with adrenaline showed higher rates of ROSC and survival rates to hospital discharge (9). On the other hand, an observational study evaluated survival outcomes from cardiac arrest before and after the execution of adrenaline in out-of-hospital cardiac arrests in Singaporean patients. In the study, only one does of I mg was permissible before transportation. The results show that there was no substantial difference in ROSC, survival to hospital admission and survival to hospital discharge (10).

A recent randomized blinded clinical trial comparing the survival to hospital discharge in patients who received pre-hospital doses of adrenaline show that; on arrival to the hospital emergency departments, patients experienced improved ROSC, including improvement in hospital admission (11, 12). However, there was no difference between the participants in the main study outcome of incidences of survival to hospital discharge. Other studies showed that for patients administered with adrenaline, the possibility of realizing ROSC was higher that patients receiving placebo.

In addition, the administration of adrenaline had associations with substantial increase in amount of patients admitted from the emergency section to the hospital discharge (13). Although more than double the number of patients that received adrenaline administration experienced survival rates in terms of hospital discharge, but this did not meet the statistical importance (14). However, there were some adverse effects, but the treatment influence of adrenaline on pre-hospital ROSC was more successful in non-shock able rhythms, when compared to shock able rhythms. However, in the two groups there was still no significant effect on the survival to hospital discharge (15).

Main Result

In most of the studies, it is apparent that adrenaline treated groups experienced an overall survival at one month or during discharge, when compared to the control groups. On the other hand, the patients with neurologically intact survival could not be differentiated between those treated with adrenaline, and those not treated. However, it was high in the group treated with adrenaline when compared to that not treated. Nonetheless, the results in this study, mainly from the prior studies are consistent with existing literature, which suggests that results are not consistent. In this regard, some studies report that there was no advantage of adrenaline in survival rates, including during discharge and neurological outcomes. On the other hand, others report otherwise, showing there was some significance of using adrenaline. Therefore, the data on this topic is inconclusive.

Discussion

Apparently, there is evidence from prior studies, which show that adrenaline can influence or rather result to increased ROSC. Nonetheless, the clinical importance of this result is inconsistent, and there are studies, which reported that there was no improvement, decrease in survival rates to hospital discharge, and decrease in favorable neurological results. In regard to the survival to discharge, the studies provide inconclusive evidence (1, 16). Alternatively, some studies, although investigators followed randomized controlled trials, which aimed at comparing adrenaline to placebo, showed an increase in the survival to discharge for patients treated with adrenaline. However, such studies were not able to use an appropriate number of subjects initially planned for the study, and this outcome did not then realize the statistical importance.

Although this is the case, it is important to consider the opportunity cost of using adrenaline. In addition, administration of adrenaline must follow an intravenous approach or the use of intra-osseous devices. This is because establishment of parental access may undermine the efficacy of other resuscitative measures, such as CPR. CPR, as suggested by prior studies, is a vital intervention with a survival rate ranging 1.23-5.01. In addition, randomized control trials, where the patients had either received intravenous drugs for cardiac life support or ACLS with no intravenous drugs did not show any difference in terms of survival to hospital discharge. This shows that although adrenaline is in use there is no reported, substantial evidence supporting its efficacy in out-of-hospital cardiac arrest. Studies also report the negative effects of adrenaline in the alteration of the cerebral, including neurological issues (17).