Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta- analyses and trial sequential analyses M.L. Fabritius, C. Strøm,

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Benefit and harm of pregabalin in acute pain treatment: a systematic review with meta- analyses and trial sequential analyses M.L. Fabritius, C. Strøm, S. Koyuncu, P. Jæger, P.L. Petersen, A. Geisler, J. Wetterslev, J.B. Dahl, O. Mathiesen British Journal of Anaesthesia Volume 119, Issue 4, Pages 775-791 (October 2017) DOI: 10.1093/bja/aex227 Copyright © 2017 The Author(s) Terms and Conditions

Fig 1 PRISMA flowchart. British Journal of Anaesthesia 2017 119, 775-791DOI: (10.1093/bja/aex227) Copyright © 2017 The Author(s) Terms and Conditions

Fig 2 Bias graph of the six bias domains. The ‘other bias’ domain consists of a financial and confirmatory bias assessment. British Journal of Anaesthesia 2017 119, 775-791DOI: (10.1093/bja/aex227) Copyright © 2017 The Author(s) Terms and Conditions

Fig 3 Forest plot of 24 h morphine consumption, including the subgroup analysis of trials with low risk of bias vs trials with unclear and high risk of bias. British Journal of Anaesthesia 2017 119, 775-791DOI: (10.1093/bja/aex227) Copyright © 2017 The Author(s) Terms and Conditions

Fig 4 Trial sequential analysis of 24 h morphine consumption from trials with low risk of bias. The minimal clinical difference was 5 mg with an α of 5% and β of 10%. The z-curve crosses the monitoring boundary for benefit after six trials, and the required information size is met. In conclusion, there is firm evidence that pregabalin reduces 24 h morphine consumption; however, we cannot rule out a reduction in 24 h morphine consumption less than the predefined minimal clinical difference of 5 mg, because the trial sequential analysis adjusted confidence interval is 3.2, 8.5 mg. British Journal of Anaesthesia 2017 119, 775-791DOI: (10.1093/bja/aex227) Copyright © 2017 The Author(s) Terms and Conditions

Fig 5 Forest plot of serious adverse events. including the subgroup analysis of trials with low risk of bias vs trials with unclear and high risk of bias. British Journal of Anaesthesia 2017 119, 775-791DOI: (10.1093/bja/aex227) Copyright © 2017 The Author(s) Terms and Conditions