Prophylactic Magnesium Supplementation and New-Onset Atrial Fibrillation in a General Critical Care Population: A Prescribing Preference Instrumental Variable Analysis

Abstract

AimsAtrial fibrillation is frequently encountered in critical illness and causes adverse effects including haemodynamic decompensation, stroke and longer hospital stay. It is common to supplement serum magnesium for the purpose of preventing new-onset atrial fibrillation. However, no randomised studies support this practice in the non-cardiac surgery critical care population, and its effectiveness is unclear. We sought to investigate the effectiveness of magnesium supplementation in preventing new-onset atrial fibrillation in a mixed critical care population.MethodsWe conducted a single centre retrospective observational study of adult critical care patients. We employed a natural experiment design, using the supplementation preference of the bedside critical care nurse as an instrumental variable.Using the electronic patient record, magnesium supplementation opportunities were defined and linked to the bedside nurse. Nurse preference for administering magnesium was obtained using multilevel modelling. The results were used to define ‘pro’ and ‘anti’ supplementation groups, which were inputted into an instrumental variable regression to obtain an estimate of the effect of magnesium supplementation.Results9,114 magnesium supplementation opportunities were analysed, representing 2,137 critical care admissions for 1,914 patients. There was significant variation in magnesium supplementation practices attributable to the individual nurse, after accounting for covariates. The instrumental variable analysis showed magnesium supplementation was associated with a 3% decreased chance of experiencing new-onset atrial fibrillation (95% CI −0.06 to −0.04, p = 0.03).ConclusionsThis study supports the strategy of routine magnesium supplementation, but further work is required to identify optimal serum magnesium targets for prophylaxis of atrial fibrillation.What’s New?Routine administration of supplemental magnesium sulphate is associated with a reduced chance of developing new-onset Atrial Fibrillation, in a general critical care cohort.This finding agrees with previous Randomised Controlled Trial results which are limited to the cardiac critical care population.This finding disagrees with previously published observational studies, which is likely due to better control of unmeasured confounding.There is significant variation in serum magnesium supplementation attributable to the individual bedside critical care nurse.Electronic health records offer the ability to evaluate the effectiveness of routinely administered treatments which lack evidence in an affordable way.Natural experiments and instrumental variable analysis offer the opportunity to derive causally robust estimations of treatment effectiveness by better accounting for unobserved confounding.

Embedded point of care randomisation for evaluating comparative effectiveness questions: PROSPECTOR-critical care feasibility study protocol

“…These values were determined from an observational study of supplementation practices at the study centre and fall within the boundaries of observed variation in practice. 11 …”

“…The restrictive arm will encourage supplementation at a serum magnesium value <0.75 mmol/L. These values were determined from an observational study of supplementation practices at the study centre and fall within the boundaries of observed variation in practice 11…”

“…Clinician behaviour will be consistent at extremes of serum magnesium measurements (never/ always supplement), but within a 'normal' range the decision to supplement will have a random component linked to the clinician's preference. 11 Variation in practice does not necessarily imply substandard care-it may be that the clinician's experience offers benefits in optimising treatment delivery, or it may be that there is no meaningful difference between treatment choices. Under ideal conditions, clinicians would be able to learn from variation and improve the quality and coverage of evidence for future patients.…”

“…These values were determined from an observational study of supplementation practices at the study centre and fall within the boundaries of observed variation in practice. 11 Randomisation will be conducted using the EHRS, which conducts simple randomisation using an internal number rule. 28 For this feasibility study, basic randomisation without additional covariate balancing will be used.…”

“…As such, clinicians vary in their threshold for routinely supplementing magnesium. Clinician behaviour will be consistent at extremes of serum magnesium measurements (never/always supplement), but within a ‘normal’ range the decision to supplement will have a random component linked to the clinician’s preference 11…”