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Three Part Question

Does [intravenous magnesium] lead to [return of spontaneous circulation] in [shock-resistant tachyarrhythmias]

Clinical Scenario

A 65 year old man suffered a witnessed out-of-hospital cardiac arrest. He received 20 minutes of basic and advances cardiac life support measures in the field. On arrival in the emergency department, the rhythm showed persistent ventricular fibrillation and he continued to be pulseless. You decide to continue another cycle of defibrillation and think of anti-arrhythmic drugs apart from correctable causes.You know that amiodarone is helpful. Your colleague mentions the use of magnesium as per ALS guidelines. Is Magnesium really helpful in return to spontaneous circulation in refractory ventricular tachyarrhythmias?

Search Strategy

MEDLINE OVID interface on the world wide web. 1966 – Dec 2005
EMBASE 1980-2005
COCHRANE Library Issue 4,2005
{exp MAGNESIUM/ or magnesium.mp} AND {exp Ventricular Fibrillation/ or ventricular fibrillation.mp OR exp Tachycardia, Ventricular/ or ventricular tachycardia.mp OR ventricular tachyarrhythmia$.mp OR exp Heart Arrest/ or cardiac arrest.mp} AND {refractory.mp. OR shock-resistant.mp. OR intractable.mp OR irreversible.mp. OR resistant.mp.OR unresponsive.mp.OR non-responsive.mp. OR pulseless.mp OR persistent.mp OR Shock-refractory} LIMIT to {human and english language}

Search Outcome

42 articles in total out of which 5 were relevant trials

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Miller et al 1995 USA	In-hospital cardiac arrest, patients in arrest after initial ACLS steps, patients with poisoning, minors, pregnancy excluded, 62 patients included;Pilot study of 5g MgSO4 administration and ACLS (n=29) versus standard ACLS (n=33)	Pilot study	Survival to discharge between two groups	1 patient in each group survived	Not a randomised controlled, blinded study, pilot study In-hospital witnessed arrests, all rhythms included Small sample size
			Resuscitation or return of spontaneous circulation	34% (3/33) in patients with ACLS and Magnesium versus 21% (6/29) only ACLS;p=0.17
Thel et al 1997 USA	All patients greater than 18 yrs, in-patient in the hospital treated for cardiac arrest;Randomised double-blind study of 2 g magesium sulphate bolus followed by infusion of 2 g/24 hours (n = 76) versus placebo (n = 80) in hospital in-patients, excluded emergency, prehospital patients with cardiac arrest, diferent rhythms included, end points of ROSC, for at least 1 hour.	Randomised controlled double-blind study	Difference in ROSC	54% in those who had Magnesium,60% no Magnesium,p=0.44	Hospital in-patients and witnessed cardiac arrests, emergency and prehospital excluded, all rhythms included Low powered study, no allocation concealment explained, at the time of arrest most patients were very ill, in ICU and with malignant diseases, time of administration not measured, low dose of magnesium given.
			24hr survival	43(Mg) vs 50%(no Mg) p=0.41
			survival to discharge	21 vs 21% p=0.98
			Karnofsky performance index	Higher in Mg group
Fatovich et al 1997 Australia	All victims of out-of-hospital cardiac arrest eligible for inclusion, excluded if dead, not receiving CPR, resuscitated, arrest due to non-cardiac etiology;Prospective randomised double blind placebo controlled trial using high dose 5g of MgSo4 (31 patients)and placebo (36 patients)	Prospective randomised double blind placebo controlled trial	ROSC	23%(Mg) and 22%(no Mg)	Out-of-hospital arrests, magnesium administered only when in hospital, different rhythms included Low powered study, no mention of randomisation method
			Survival to leave ED	13% (Mg)vs 11%(no Mg)
			Survival to leave hospital	1 patient (Mg)
Allegra 2001 USA	All patients with non-traumatic cardiac arrest greater than 18 and had VF refractory to 3 electroshocks in prehospital set-up. Total of 116 patients, 58 Mg/58 placebo, enrolled between 1992 and 1996. 109 available for analysis.	Prospective double blind, placebo controlled multi-center prehospital clinical trial; 58 received magnesium and 58 placebo	Time to study drug administration	25.5 min for magnesium group, 30.4 for placebo group	Time of administration of study drug greater than 25 mins, low dose of magnesium administered, low powered study. Study closed prematurely as it became difficult to enroll patients when Magnesium became class IIB agent in AHA guidelines for VF treatment
			ROSC	placebo 18.5 vs Mg 25.5%, P=0.38
			Admission	16.7 (placebo)vs 16.4%(Mg) P=1.0
			Discharge	placebo 3.7% vs Mg 3.6%, P=1.0
T B Hassan, C Jagger, D B Barnett 2002 UK	Patients in Cardiac Arrest with refractory or recurrent VF treated in the prehospital phase by the county emergency medical services and/or in the A&E department. 52 given Mg, 53 given placebo.	A randomised, double blind, placebo controlled trial	ROSC	17%(Mg) and 13% (placebo)(CI-10% to +18%)	Possible that a type II error occurred, dose of magnesium given during CA may have been inadequate. Individual factors such as the incidence of bystander CPR, the response time to the first defibrillatory shock, protocol violations and even the aggressiveness of care provided in hospital both within the A&E department and particularly on the ICU can have major influences. Study population is small, response time could have been a significant factor in magnesium's seeming lack of efficacy in treating refractory VF in this study population
			Patients alive to discharge	4%(Mg) and 2% (placebo)( CI –7% to +11%)
			Odds Ratio for ROSC in patients treated with Mg versus placebo	1.69 (0.54 to 5.30)

Comment(s)

Magnesium use in refractory ventricular tachyarrhythmias gained interest after case reports by Tobey, Craddock, Baraka and others which showed return of spontaneous circulation and neurological intact discharge. However, subsequent randomised trials dampened the enthusiasm. Based on current evidence, magnesium does not seem to effect return of spontaneous circulation or survival from hospital with neurologically intact parameters. However, the trials are all low powered with different other methodological issues involved. These should be addressed in large multi-centred trials before any further use. Ethical approval for such large multi-centred trials with different EMS systems will always be a major stumbling block.

Clinical Bottom Line

Magnesium has not been conclusively shown to be useful in shock-resistant tachyarrhythmias when measured against clinically important outcomes.

References

1. Miller B. Craddock L. Hoffenberg S. Heinz S. Lefkowitz D. Callender ML. Battaglia C. Maines, Masick D Pilot study of intravenous magnesium sulfate in refractory cardiac arrest: safety data and recommendations for future studies. Resuscitation 30(1):3-14, 1995 Aug.
2. Thel MC, Armstrong AL, McNulty SE, Califf RM, O'Connor CM Randomized trial of magnesium in in-hospital cardiac arrest Lancet 350(9087):1272-6, 1997 Nov 1
3. Fatovich DM. Prentice DA. Dobb GJ. Magnesium in cardiac arrest (The MAGIC Trial). Resuscitation 35(3):237-41, 1997 Nov
4. Allegra J. Lavery R. Cody R. Birnbaum G. Brennan J. Hartman A. Horowitz M. Nashed A. Yablonski M. Magnesium sufate in the treatment of refractory venticular fibrillation in the prehospital setting. Resuscitation. 49(3):245-9, 2001 Jun
5. Hassan TB. Jagger C. Barnett DB. A randomised trial to investigate the efficacy of magnesium sulphate for refractory ventricular fibrillation. Emergency Medicine Journal 19(1):57-62, 2002 Jan.