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Pharmacotherapy for the Prevention of Chronic Pain after Surgery in Adults

Abstract and Introduction


Background: Chronic postsurgical pain can severely impair patient health and quality of life. This systematic review update evaluated the effectiveness of systemic drugs to prevent chronic postsurgical pain.

Methods: The authors included double-blind, placebo-controlled, randomized controlled trials including adults that evaluated perioperative systemic drugs. Studies that evaluated same drug(s) administered similarly were pooled. The primary outcome was the proportion reporting any pain at 3 or more months postsurgery.

Results: The authors identified 70 new studies and 40 from 2013. Most evaluated ketamine, pregabalin, gabapentin, IV lidocaine, nonsteroidal anti-inflammatory drugs, and corticosteroids. Some meta-analyses showed statistically significant—but of unclear clinical relevance—reductions in chronic postsurgical pain prevalence after treatment with pregabalin, IV lidocaine, and nonsteroidal anti-inflammatory drugs. Meta-analyses with more than three studies and more than 500 participants showed no effect of ketamine on prevalence of any pain at 6 months when administered for 24 h or less (risk ratio, 0.62 [95% CI, 0.36 to 1.07]; prevalence, 0 to 88% ketamine; 0 to 94% placebo) or more than 24 h (risk ratio, 0.91 [95% CI, 0.74 to 1.12]; 6 to 71% ketamine; 5 to 78% placebo), no effect of pregabalin on prevalence of any pain at 3 months (risk ratio, 0.88 [95% CI, 0.70 to 1.10]; 4 to 88% pregabalin; 3 to 80% placebo) or 6 months (risk ratio, 0.78 [95% CI, 0.47 to 1.28]; 6 to 68% pregabalin; 4 to 69% placebo) when administered more than 24 h, and an effect of pregabalin on prevalence of moderate/severe pain at 3 months when administered more than 24 h (risk ratio, 0.47 [95% CI, 0.33 to 0.68]; 0 to 20% pregabalin; 4 to 34% placebo). However, the results should be interpreted with caution given small study sizes, variable surgical types, dosages, timing and method of outcome measurements in relation to the acute pain trajectory in question, and preoperative pain status.

Conclusions: Despite agreement that chronic postsurgical pain is an important topic, extremely little progress has been made since 2013, likely due to study designs being insufficient to address the complexities of this multifactorial problem.


Chronic postsurgical pain has been recognized as a disabling complication that can have a severe impact on patient health and quality of life, with pain that can sometimes last for a significant amount of time after surgery. On average, 10% of patients undergoing common surgical procedures will suffer from chronic pain.[1–3] Given the difficulty in managing chronic postsurgical pain, many efforts to prevent the transition from acute to chronic pain have been evaluated, including perioperative administration of various systemic pharmacologic interventions. The aim of this review is to synthesize available evidence from placebo-controlled, randomized controlled trials on the effectiveness and safety of systemically administered drugs that aim to prevent the development of chronic postsurgical pain in adults undergoing elective surgeries. This systematic review is the first update of an original review we published in 2013[4] and it will describe results of an updated search of new studies published since then. The rationale for updating the review is to provide the most current and best available evidence to inform clinical decision-making for this highly relevant issue.

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