Magnesium for prophylaxis against AF.
Prophylaxis with magnesium is an effective strategy to minimise the incidence of AF for patients undergoing cardiac surgery. This may safely be given in addition to other strategies to reduce the incidence of AF.
(Grade A recommendation based on level 1a and level 1b studies)
One acceptable strategy for effective prophylaxis with magnesium is 6 mmol magnesium
sulphate infusion pre-operatively, just after cardiopulmonary bypass and once daily for 4 days after surgery.
(Grade B recommendation based on an individual level 1b study)
Evidence was sought for whether magnesium reduces the incidence of post-operative AF in patients undergoing cardiac surgery. This search is fully documented in the ICVTS (Rostron et al. ) together with a summary of all identified papers. One hundred and thirteen papers were identified using the presented search strategy. Fromthese, 21 papers represented the best evidence on this topic. Two further meta-analyses were also identified after this search was conducted [34,35].
We identified 20 RCTs that addressed this issue and 3 meta-analyses. One meta-analysis summarised data on 2069 patients from all but six of the RCTs that we identified. The meta-analysis was performed by Shiga et al.  in 2004, summarising papers that contained magnesium alone as prophylaxis and compared it to placebo treatment. Twenty three percent of patients in the magnesium groups suffered a supraventricular arrhythmia compared with 31% in the placebo group ( p = 0.002). This gives a NNT of 13 to prevent one episode of supraventricular tachyarrhythmia (SVT). In addition, they found a significant reduction in the incidence of ventricular arrhythmias with a NNT of 14 to prevent one episode of ventricular tachyarrhythmia (VT). Shiga et al. also summarised the complications reported in 648 patients. They found no episodes of bradycardia or hypotension. However, important differences were found between all these studies and no one prophylactic regime was found to be superior to another. Regimes ranged from a single dose of 5 mmol in the cardioplegia solution to 110 mmol over the course of 3 days.
The second meta-analysis published in 2005  summarised 20 studies with 2490 patients. They found that the incidence of post-operative AF reduced from 28% to 18% (OR 0.54, 95% CI 0.38—0.75). They also summarised the effect on length of stay and mortality but found no significant difference. Again, they did not recommend one specific magnesium prophylactic regime.
The most recent meta-analysis summarised only eight RCTs that compared magnesium with placebo . They also found a highly significant reduction in relative risk with the addition of magnesium (RR 0.64, 95% CI: 0.47— 0.87).
There were six studies that investigated over 200 patients. Toraman et al.  in 2001 performed an RCT in 200 patients, giving them either 6 mmol of magnesium both pre-operatively and post-operatively or placebo. Only 2 (2%) of patients receiving magnesium went into AF compared with 21 (21%) in the control group. Unfortunately, patients receiving bblockers or digoxin were excluded.
Forlani et al.  performed an RCT in 2001, separating 207 patients into four groups. Patients received either sotalol 80 mg bd or magnesium 1.5 g orally for 6 days postoperatively or both or neither treatment. Only 1 of 52 patients who received both treatments went into AF compared with 19 of 50 control patients.
Hazelrigg et al.  randomised 105 patients to receive 80 mg/kg of magnesium pre-operatively, then 8 mg/(kg h) post-operatively for 48 h or placebo in 97 patients. Thirtytwo treatment patients went into AF compared with 41 control patients, which was a non-significant trend towards benefit. However, the reduction in AF was significantly different between groups on day 1.
Yeatman et al.  performed the largest study on magnesium prophylaxis, with 400 patients randomised in a double blind fashion to receive 40 mmol of 2 mmol/ml magnesium sulphate in the cardioplegia solution or controls. They found that the incidence of AF was 22% in the magnesium group compared with 29% in controls, which was non-significant, although the findings were significant in a subset analysis of urgent patients. The authors acknowledged that their dose of magnesium only produced a concentration of 5 mmol/l of cardioplegia, when actually they should have used a higher dose to obtain a concentration nearer 15 mmol/l of cardioplegia.
Bert et al.  performed a multi-arm study in 387 patients randomised into six groups of prophylaxis including 2 g of magnesium pre-operatively, post-operatively and for 4 days after the operation. Unfortunately, addition of magnesium had no beneficial effect as compared with b-blockers, digoxin or controls.
Kaplan et al.  performed a study in 200 patients, giving 3 g of magnesium intravenously pre-operatively and postoperatively and for 3 days. No significant difference was found overall, although in a sub-analysis of patients who had low pre-operative serum magnesium, a significant reduction in AF was demonstrated.
With regard to which regime should be employed, Yeatman et al. , who performed the largest study, recommend 15 mmol/l in the cardioplegia solution, although they used a dose smaller than this in their study. Toraman et al.  found the greatest beneficial effect in their large study of 200 patients. They used 6 mmol magnesium sulphate infusion in 100 ml 0.9% NaCl solution (at 25 ml/h) the day before surgery, just after cardiopulmonary bypass and once daily for 4 days after surgery. As this study demonstrates the largest benefit in a well-conducted study, perhaps this should be regarded as the optimal regime so far investigated.
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Autorisatiedatum en geldigheid
Laatst beoordeeld : 26-11-2010
Laatst geautoriseerd : 26-11-2010
Geplande herbeoordeling : 01-11-2015
Revisiedatum uiterlijk november 2015
Deze richtlijn is mede gebaseerd op de EACTS-guidelines on the prevention and management of de novo atrial fibrillation after cardiac and thoracic surgery.
Notitie specifiek met betrekking op de Nederlandse situatie:
Lees ipv Warfarine: Coumarine-derivaten
Deze notitie vormt een integraal onderdeel van de Engelstalige tekst van de hierbij behorende richtlijn.
Doel en doelgroep
This guideline covers the prophylaxis and treatment of de novo AF in adults undergoing cardiac and thoracic surgery. It includes recommendations for intra-operative strategies to
minimise the incidence of AF, the pharmacological treatment of AF and recommendations for anticoagulation of these patients. In addition, monitoring and ward management
of these patients are also addressed. It excludes recommendations for the surgical management of patients coming to surgery with chronic AF, and recommendations for
patients in chronic AF not undergoing cardiothoracic surgery.
- Joel Dunning (James Cook University Hospital, Middlesbrough, UK)
- Tom Treasure (Guy’s Hospital, London, UK)
- Michael Versteegh (Leiden University Medical Center, The Netherlands)
- Samer A.M. Nashef (Papworth Hospital, Cambridge, UK)
on behalf of the EACTS Audit and Guidelines Committee
The EACTS Audit andGuidelineCommittee is grateful to thefollowing authors for assisting with the literature reviewprocess by publishing Best Evidence Topics for the ICVTS:
Muneer Amanullah, Ali Behranwala, Phil Botha, Mohammed Hanif, Noman Khasati, Graham Morritt, Darbhamulla Nagarajan, Mohammed Nouraei, Brian Nyawo, Savvas Omorphos, Anish Patel, Brian Prendergast, Shahzad Raja, Jagan Rao, Andrew Ronald, Anthony Rostron, Aliu Sanni, Vivek Shrivastava.
This guideline comprises several novel aspects in the methodology employed in the derivation of this document. Many guidelines are based on a single systematic review and
multiple clinical questions are then answered on the basis of the papers found from this one review. In contrast, we felt that it was important to perform a full literature review for
every single question addressed in order to maximise the robustness of the guideline. We used a structured systematic review protocol named ‘Best Evidence Topics’ to construct each review, where the search strategy, results of the search and a full appraisal of all papers are published in a structured format. The details of this protocol are described in the Interactive Cardiovascular and Thoracic Surgery (ICVTS) . Guidelines often fall short of expectations due to a failure to consult those clinicians who are most likely to
use them. For this guideline, every literature review has already been published in full in the ICVTS. Every topic was published online and clinicians were able to post comments
on the topic over a 2-month period. These comments were then published together with the full paper in the ICVTS and are now available to all readers in full text online at www.icvts.org.
These guidelines assess individual studies according to recommendations developed and refined over time  and previously used in the specialty . Briefly, level 1 papers are
randomised controlled trials, level 2 papers are cohort studies, level 3 papers are case-controlled studies or small cohort studies and level 4 studies are experimental papers.
The ‘b’ suffix implies that the study is an original article at this level and the ‘a’ suffix implies that the paper is a systematic review or meta-analysis of papers at that level (further details are available from the website of the Oxford Centre for Evidence based Medicine: http://www.cebm.net/levels_of_evidence.asp 2001).
Systematic literature review was up to the end of 2005. Once recommendations are made, they are graded according to the quality of papers used to come to our conclusion:
- Grade A evidence: based on multiple level 1a or level 1b papers
- Grade B evidence: based on multiple level 2a/2b papers or individual level 1a/1b papers
- Grade C evidence: based on multiple level 3a/3b papers or individual level 2a/2b papers
- Grade D evidence: based on individual level 3a/3b papers or level 4 papers
- Grade E evidence: based on expert consensus in the absence of acceptable papers