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NIHR Signal Intravenous magnesium can reduce shivering in patients after surgery

Published on 24 April 2019

doi: 10.3310/signal-000765

An infusion of magnesium, given during or immediately after surgery, reduces the proportion of patients who experience shivering in the operating theatre or in recovery from 23% to 9.9%.

Shivering is unpleasant for the patient and may place strain on the cardiovascular system, as it increases oxygen use. A review of 64 trials found that intravenous magnesium was effective compared to placebo without any reported adverse effects.

In the UK, frequent temperature checks and active warming are routinely used in operating theatres. Nevertheless, shivering is still common even when body temperature is normal. It is unclear how many of the trials used active warming in addition to magnesium, so this may limit generalisability of the studies to UK practice.

Intravenous magnesium should be added to the options for managing patients at risk of perioperative shivering, although this review was not able to define an optimum dose or timing.

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Why was this study needed?

Despite efforts to keep patients warm and reduce hypothermia, shivering is common among surgical patients, especially those who are younger, who have a lower core temperature, and where surgery is of longer duration.

Previous, much smaller meta-analyses of trials that studied the effect of magnesium on perioperative shivering have had conflicting results. Although other drugs have been tested, they are more expensive and may have safety issues.

This review used a broader search methodology and did not restrict to English language trials, to provide a more conclusive answer to the question of whether magnesium prevents shivering.

What did this study do?

The authors searched for any randomised clinical trials comparing magnesium to placebo or no treatment in surgical patients with shivering as an outcome, even where shivering was not the primary outcome. They conducted a systematic review and meta-analysis, then used GRADE methodology to assess the strength of their findings.

Because of the numbers of studies included (64 studies with 4,303 participants), they were able to look at the effects of different routes of administration of magnesium, and conduct trial sequential analysis to ascertain whether further studies were likely to alter their findings. They also carried out sensitivity analyses, restricting the analysis to studies at low risk of bias, to see whether this affected the results.

What did it find?

  • The overall incidence of shivering was 9.9% for patients who received magnesium, and 23% for patients who did not. This represented a relative risk reduction of 58% (risk ratio [RR] 0.42, 95% confidence interval [CI] 0.33 to 0.52; 64 trials, 4,303 participants).
  • In sub-group analysis by route of administration, shivering was reduced when magnesium was administered by intravenous infusion (RR 0.39, 95% CI 0.29 to 0.54; 2,124 participants, 35 trials); by epidural (RR 0.24, 95% CI 0.13 to 0.43; 880 participants, 12 trials) and intrathecally – injected directly into the cerebrospinal fluid (RR 0.64, 95% CI 0.43 to 0.96; 1,120 participants, 16 trials).
  • Trial sequential analysis of studies at low risk of bias showed that there is sufficient data to conclude that intravenous magnesium reduces shivering in perioperative patients and this is unlikely to change with further studies. However, the analysis found there was insufficient data to be sure of the effects of epidural or intrathecal administration.
  • The study found no increase in adverse events including time to extubation, length of stay in a post-anaesthesia care unit, sedation, nausea, itching, low heart rate or low blood pressure. No serious adverse events were noted in any of the studies.

What does current guidance say on this issue?

The NICE 2008 guideline (updated in 2016) makes extensive recommendations about the monitoring of temperature for patients undergoing surgery, use of active warming, and other measures to reduce hypothermia. These include maintaining the ambient temperature of the operating theatre above 21 degrees when the patient is exposed, and ensuring the patient is covered as much as possible. The guideline does not address shivering specifically, nor the use of magnesium to prevent or treat it.

What are the implications?

While temperature measurement and warming are the most important interventions to reduce the risk of hypothermia, magnesium also seems to lower the risk of shivering. Unfortunately, the study was not able to look at the impact of magnesium alongside good temperature management. Nevertheless, it gives an additional management option for anaesthetists to consider, especially in the treatment of patients at high risk of shivering.

Citation and Funding

Kawakami H, Nakajima D, Mihara T et al. Effectiveness of magnesium in preventing shivering in surgical patients: a systematic review and meta-analysis. Anesth Analg. 2019; Feb 8. doi: 10.1213/ANE.0000000000004024. [Epub ahead of print].

This study was funded by Yokohama City University in Japan.

Bibliography

NICE. Hypothermia: prevention and management in adults having surgery. CG65. London: National Institute for Health and Care Excellence; 2008 (updated 2016).

Why was this study needed?

Despite efforts to keep patients warm and reduce hypothermia, shivering is common among surgical patients, especially those who are younger, who have a lower core temperature, and where surgery is of longer duration.

Previous, much smaller meta-analyses of trials that studied the effect of magnesium on perioperative shivering have had conflicting results. Although other drugs have been tested, they are more expensive and may have safety issues.

This review used a broader search methodology and did not restrict to English language trials, to provide a more conclusive answer to the question of whether magnesium prevents shivering.

What did this study do?

The authors searched for any randomised clinical trials comparing magnesium to placebo or no treatment in surgical patients with shivering as an outcome, even where shivering was not the primary outcome. They conducted a systematic review and meta-analysis, then used GRADE methodology to assess the strength of their findings.

Because of the numbers of studies included (64 studies with 4,303 participants), they were able to look at the effects of different routes of administration of magnesium, and conduct trial sequential analysis to ascertain whether further studies were likely to alter their findings. They also carried out sensitivity analyses, restricting the analysis to studies at low risk of bias, to see whether this affected the results.

What did it find?

  • The overall incidence of shivering was 9.9% for patients who received magnesium, and 23% for patients who did not. This represented a relative risk reduction of 58% (risk ratio [RR] 0.42, 95% confidence interval [CI] 0.33 to 0.52; 64 trials, 4,303 participants).
  • In sub-group analysis by route of administration, shivering was reduced when magnesium was administered by intravenous infusion (RR 0.39, 95% CI 0.29 to 0.54; 2,124 participants, 35 trials); by epidural (RR 0.24, 95% CI 0.13 to 0.43; 880 participants, 12 trials) and intrathecally – injected directly into the cerebrospinal fluid (RR 0.64, 95% CI 0.43 to 0.96; 1,120 participants, 16 trials).
  • Trial sequential analysis of studies at low risk of bias showed that there is sufficient data to conclude that intravenous magnesium reduces shivering in perioperative patients and this is unlikely to change with further studies. However, the analysis found there was insufficient data to be sure of the effects of epidural or intrathecal administration.
  • The study found no increase in adverse events including time to extubation, length of stay in a post-anaesthesia care unit, sedation, nausea, itching, low heart rate or low blood pressure. No serious adverse events were noted in any of the studies.

What does current guidance say on this issue?

The NICE 2008 guideline (updated in 2016) makes extensive recommendations about the monitoring of temperature for patients undergoing surgery, use of active warming, and other measures to reduce hypothermia. These include maintaining the ambient temperature of the operating theatre above 21 degrees when the patient is exposed, and ensuring the patient is covered as much as possible. The guideline does not address shivering specifically, nor the use of magnesium to prevent or treat it.

What are the implications?

While temperature measurement and warming are the most important interventions to reduce the risk of hypothermia, magnesium also seems to lower the risk of shivering. Unfortunately, the study was not able to look at the impact of magnesium alongside good temperature management. Nevertheless, it gives an additional management option for anaesthetists to consider, especially in the treatment of patients at high risk of shivering.

Citation and Funding

Kawakami H, Nakajima D, Mihara T et al. Effectiveness of magnesium in preventing shivering in surgical patients: a systematic review and meta-analysis. Anesth Analg. 2019; Feb 8. doi: 10.1213/ANE.0000000000004024. [Epub ahead of print].

This study was funded by Yokohama City University in Japan.

Bibliography

NICE. Hypothermia: prevention and management in adults having surgery. CG65. London: National Institute for Health and Care Excellence; 2008 (updated 2016).

Effectiveness of Magnesium in Preventing Shivering in Surgical Patients: A Systematic Review and Meta-analysis

Published on 8 February 2019

Kawakami, H.,Nakajima, D.,Mihara, T.,Sato, H.,Goto, T.

Anesth Analg , 2019

BACKGROUND: Clinical trials regarding the antishivering effect of perioperative magnesium have produced inconsistent results. We conducted a systematic review and meta-analysis with Trial Sequential Analysis to evaluate the effect of perioperative magnesium on prevention of shivering. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Central Register of Controlled Trials, and 2 registry sites for randomized clinical trials that compared the administration of magnesium to a placebo or no treatment in patients undergoing surgeries. The primary outcome of this meta-analysis was the incidence of shivering. The incidence of shivering was combined as a risk ratio with 95% CI using a random-effect model. The effect of the route of administration was evaluated in a subgroup analysis, and Trial Sequential Analysis with a risk of type 1 error of 5% and power of 90% was performed. The quality of each included trial was evaluated, and the quality of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation approach. We also assessed adverse events. RESULTS: Sixty-four trials and 4303 patients (2300 and 2003 patients in magnesium and control groups, respectively) were included. The overall incidence of shivering was 9.9% in the magnesium group and 23.0% in the control group (risk ratio, 0.42; 95% CI, 0.33-0.52). Subgroup analysis revealed that the incidence of shivering was lower with IV (risk ratio, 0.29; 95% CI, 0.29-0.54; Grading of Recommendation Assessment, Development, and Evaluation, moderate), epidural (risk ratio, 0.24; 95% CI, 0.13-0.43; Grading of Recommendation Assessment, Development, and Evaluation, low), and intrathecal administration (risk ratio, 0.64; 95% CI, 0.43-0.96; Grading of Recommendation Assessment, Development, and Evaluation, moderate). Only trials with low risk of bias were included for Trial Sequential Analysis. The Z-cumulative curve for IV magnesium crossed the Trial Sequential Analysis monitoring boundary for benefit even though only 34.9% of the target sample size had been reached. The Z-cumulative curve for epidural or intrathecal administration did not cross the Trial Sequential Analysis monitoring boundary for benefit. No increase in adverse events was reported. CONCLUSIONS: Perioperative IV administration of magnesium effectively reduced shivering and Trial Sequential Analysis suggested that no more trials are required to confirm that IV magnesium effectively reduces shivering.

Expert commentary

This meta-analysis by Kawakami has important implications for those caring for patients in the perioperative setting.  As well as being unpleasant for patients as they recover from surgery and anaesthesia, shivering is a physiological nuisance and consumes energy which would be better spent elsewhere in the healing and recovery process.

Intravenous magnesium sulphate has long been suspected to reduce the incidence of postoperative shivering, but the evidence has been difficult to evaluate because trials have been small and inconsistent.  This meta-analysis reveals that intravenous magnesium sulphate reduces the risk of shivering to less than half of control with no difference in incidence of adverse effects.

Magnesium is a cheap and safe therapy so clinicians working in this area should feel more confident in using it.

Dr Andrew Farmery, Associate Professor, Head of the Nuffield Division of Anaesthetics, Nuffield Department of Clinical Neurosciences, University of Oxford

The commentator declares no conflicting interests

Expert commentary

Many patients experience significant shivering following general or regional anaesthesia. As well as being unpleasant and sometimes painful, perioperative shivering increases skeletal muscle and myocardial oxygen demand.

This meta-analysis suggests that prophylactic intravenous magnesium reduces the risk of perioperative shivering compared to placebo or no treatment. The study was unable to estimate the optimal magnesium dose.

The study’s conclusions should be interpreted with caution: the impact of magnesium in the context of the routine core body temperature measurement and application of active warming techniques during surgery remains unclear. The mechanism by which magnesium may exert its effect on shivering remains uncertain.

Dr David W Hewson, Consultant Anaesthetist, Nottingham University Hospitals NHS Trust; Honorary Assistant Professor, University of Nottingham

The commentator declares no conflicting interests