Randomised trial of magnesium in in-hospital cardiac arrest

doi:10.1016/S0140-6736(97)05048-4

The Lancet

Volume 350, Issue 9087, 1 November 1997, Pages 1272-1276

https://doi.org/10.1016/S0140-6736(97)05048-4 Get rights and content

Summary

Background

The apparent benefit of magnesium in acute myocardial infarction, and the persistently poor outcome after cardiac arrest, have led to use of magnesium in cardiopulmonary resuscitation. Because few data on its use in cardiac arrest were available, we undertook a randomised placebo-controlled trial (MAGIC trial).

Methods

Patients treated for cardiac arrest by the Duke Hospital code team were randomly assigned intravenous magnesium (2 g [8 mmoles] bolus, followed by 8 g [32 mmoles] over 24 h; 76 patients) or placebo (80 patients). Only patients in intensive care or general wards were eligible; those whose cardiac arrest occurred in emergency, operating, or recovery rooms were excluded. The primary endpoint was return of spontaneous circulation, defined as attainment of any measurable blood pressure or palpable pulse for at least 1 h after cardiac arrest. The secondary endpoints were survival to 24 h, survival to hospital discharge, and neurological outcome. Analysis was by intention to treat.

Findings

There were no significant differences between the magnesium and placebo groups in the proportion with return of spontaneous circulation (41 [54%] vs 48 [60%], p=0·44), survival to 24 h (33 [43%] vs 40 [50%], p=0·41), survival to hospital discharge (16 [21%] vs 17 [21%], p=0·98), or Glasgow coma score (median 15 in both).

Interpretation

Empirical magnesium supplementation did not improve the rate of successful resuscitation, survival to 24 h, or survival to hospital discharge overall or in any subpopulation of patients with in-hospital cardiac arrest.

Introduction

Despite many refinements in techniques, survival after cardiac arrest has not improved since Kouwenhoven and colleagues introduced modern cardiopulmonary resuscitation in 1960.¹ Survival after prehospital and inhospital cardiac arrest remains about 15%, though reported results vary from 1% to 30%.2, 3, 4 Investigations of new pharmacological and mechanical interventions designed to improve survival have been disappointing.^3,5–7

Evidence that magnesium dilates coronary arteries, inhibits platelet activity, suppresses automaticity, and inhibits calcium influx into myocytes suggests that magnesium supplementation is cardioprotective.⁸ The use of magnesium was supported by the results of randomised trials that showed improved survival in patients treated with magnesium after acute myocardial infarction.9, 10, 11, 12 Magnesium supplementation in patients with hypomagnesaemia is supported by the association of low magnesium concentrations with cardiac arrhythmias, sudden death, and low survival after myocardial infarction.¹³ Nevertheless, evidence for a clinical benefit of empirical magnesium supplementation in cardiac arrest is limited to retrospective reports that describe successful resuscitation after magnesium in refractory cases;⁹ there has been no randomised controlled trial. Despite the lack of data, the 1992 American Heart Association guidelines for Advanced Cardiac Life Support prescribed magnesium supplementation for severe refractory ventricular fibrillation and tachycardia.¹⁴ In a randomised, placebo-controlled trial (the MAGIC trial), we have assessed the efficacy of empirical magnesium supplementation in patients with in-hospital cardiac arrest, with return of spontaneous circulation as the primary outcome and survival to hospital discharge as a secondary endpoint.

Section snippets

Methods

All hospital inpatients who were at least 18 years old and treated for cardiac arrest by the Duke Hospital code team were eligible for enrolment. Cardiac arrest was defined as the cessation of cardiac mechanical activity confirmed by the absence of consciousness (no response to noxious stimuli), spontaneous respiration, blood pressure, and pulse (in accordance with accepted guidelines).¹⁵ Patients in the intensive-care units and general wards were eligible (whether or not they were on central

Results

Between August 1, 1993, and May 1, 1996, 156 patients (89 men, 67 women) with a median age of 65 years (IQR 53–73) were enrolled (figure). 76 (49%) were randomly assigned treatment with magnesium and 80 (51%) were assigned placebo. All patients were unresponsive, apnoeic, and hypotensive or had no pulse at enrolment in the study. There were no crossovers in study drug administration. Once enrolled, no patient was excluded from the analysis, withdrawn, or lost to follow-up.

The most common

Discussion

Our study showed no improvement in likelihood of resuscitation, 24 h survival, or survival to hospital discharge in patients with cardiac arrest who were treated wtih empirical magnesium supplementation compared with placebo. Analysis of predefined subgroups did not identify patients who would be likely to benefit from magnesium administration. In a prespecified analysis, the quality of life and functional status in patients assigned magnesium who survived to hospital discharge was

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Bicarbonate, calcium, and magnesium are commonly used during in-hospital cardiac arrest. Whether these drugs are associated with survival in cardiac arrest patients is uncertain.
This was an observational study using data from the Get With The Guidelines registry. Adult patients with an in-hospital cardiac arrest between January 2008 and December 2021 were included. An instrumental variable approach was used based on hospital preferences for bicarbonate, calcium, and magnesium, respectively. The primary outcome was survival to hospital discharge.
A total of 319,230 patients were included. The median age was 66 years, 59% patients were male, and 85% patients presented with a non-shockable rhythm. Bicarbonate was administered in 58% patients, calcium in 33% patients, and magnesium in 10% patients. When considering drug use in the previous cardiac arrest patient at a given hospital as an instrument, the absolute difference in survival to hospital discharge was estimated at −14.2% (95% CI, −19.9 to −8.6) for bicarbonate, −3.0% (95% CI, −8.6 to 2.6) for calcium, and 10.7% (95% CI, −0.8 to 22.2) for magnesium as compared to no drug. When considering the proportion of drug use within the past year at a given hospital as an instrument, the confidence intervals were very wide, making the results difficult to interpret.
In this analysis, the results for bicarbonate, calcium, and magnesium were inconclusive due to wide confidence intervals and inconsistencies in estimates across instrumental variables. Randomized trials are needed to investigate the effect of these drugs on patient outcomes.
The Pharmacologic Management of Cardiac Arrest
2023, Emergency Medicine Clinics of North America
Important unanswered research questions related to torsades de pointes
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The previous chapters have outlined the cellular and clinical aspects of both the acquired and congenital long QT syndromes (LQTS) that predispose to torsades de pointes (TdP). The genomic medicine era is a promising time for the development of improved diagnostics and therapeutics in this field. However, many questions related to the basic mechanisms, population incidence and clinical management of TdP remain unanswered despite decades of study. Even basic issues, like the best electrocardiogram (ECG) screening practices, the most appropriate QT interval correction formula to use, and the ethnicity and sex-based differences that exist remain unclear. Additionally, there is a lack of controlled studies on TdP in the literature. In part, this is driven by a poor ability, without prolonged monitoring, to detect TdP events, which may be fatal in the community or too transient in nature to diagnose. Wearable ECG technologies and clinical decision support systems will likely help to bridge some of the gaps that exist in drug safety monitoring and defining TdP prevalence. Finally, novel genomic and precision guided therapies require further evaluation. Ribonucleic acid (RNA) interference therapies and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas-9 genome editing are exciting new avenues to pursue. However, these technologies have not been evaluated in humans with LQTS or TdP. Their anticipated cost coupled with the complicated genetic architecture of the QT interval may impose practical barriers to utilization in some circumstances. In this final chapter, these and several other unanswered questions in LQTS and TdP will be addressed, and four key domains are presented that may guide future studies.
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.
Adult post-cardiac arrest interventions: An overview of randomized clinical trials
2020, Resuscitation
To provide an overview of published and registered trials related to post-cardiac arrest interventions.
We searched PubMed and the International Clinical Trials Registry Platform for randomized clinical trials in adults specifically addressing a post-cardiac arrest intervention.
We identified 65 manuscripts reporting randomized clinical trials. The majority of the trials were published within the last 10 years and the sample sizes were generally low with a median of 90 participants (quartiles: 49, 262; range: 9, 1359). The majority of the trials were conducted in out-of-hospital cardiac arrest (79%), while only 6% were conducted specifically in in-hospital cardiac arrest and 15% included both in- and out-of-hospital cardiac arrest.
We identified 48 registered trials online. The median target sample size is 100 participants (quartiles: 60, 400; range: 20, 1900). The majority of trials are enrolling patients with out-of-hospital cardiac arrest (71%) while 6% specifically focuses on in-hospital cardiac arrest.
This review provides an overview of published and registered trials addressing post-cardiac arrest interventions. We believe this information will be relevant to guide future research.
Analysis of the 2018 American Heart Association Focused Update on Advanced Cardiovascular Life Support Use of Antiarrhythmic Drugs During and Immediately After Cardiac Arrest
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Citation Excerpt :
Prospective randomization occurred in the 4 studies that studied the neuroprotective properties of magnesium during elective cardiac surgery.40–43 Patients were randomized during treatment in the studies of the effectiveness of magnesium during cardiac arrest.44–46 Two studies gave a bolus dose of magnesium either en route or on arrival to the emergency department, 3 studies gave a bolus dose followed by infusion, and 2 studies administered an infusion only.41,42,44–46

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ArticlesRandomised trial of magnesium in in-hospital cardiac arrest

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Results

Discussion

Am J Emerg Med

Lancet

Lancet

Resuscitation

Ann Thorac Surg

Ann Thorac Surg

Am J Emerg Med

Closed-chest cardiac massage

JAMA

A randomized clinical trial of high-dose epinephrine and norepinephrine vs standard-dose epinephrine in prehospital cardiac arrest

JAMA

In-hospital cardiopulmonary resuscitation: survival; in 1 hospital and literature review

Medicine (Baltimore)

Interposed abdominal compression-cardiopulmonary resuscitation and resuscitation outcome during asystole and electromechanical dissociation

Circulation

The Ontario trial of active compression-decompression cardiopulmonary resuscitation for in-hospital and prehospital cardiac arrest

JAMA

Association of drug therapy with survival in cardiac arrest: limited role of advanced cardiac life support drugs

Acad Emerg Med

Possible pharmacological actions of magnersium in acute myocardial infarction

Br J Clin Pharmacol

Magnesium in acute myocardial infarction

Coron Artery Dis

Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality: meta-analysis of magnesium in acute myocardial infarction

Circulation

Articles
Randomised trial of magnesium in in-hospital cardiac arrest