Pharmacotherapy for the Prevention of Chronic Pain after Surgery in Adults: An Updated Systematic Review and Meta-analysis

Abstract

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. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Impact of Ketamine on Opioid Use and Persistent Pain After Cytoreductive Surgery with Hyperthermic Chemotherapy

“… 26 However, most recent evidence contradicts Chaparro’s findings. 27 Here, we could not demonstrate a significant difference in chronic pain after CRS-HIPEC surgery between those treated with and without ketamine. However, our analysis showed that 15.9% of the patients not receiving ketamine complained of chronic pain (at 12 months) in comparison to 4% in the ketamine group, suggesting a possible protective effect.…”

Input-dependent synaptic suppression by pregabalin in the central amygdala in male mice with inflammatory pain

“…This characteristic would imply that PGB might affect mechanisms involved not simply in the transmission of nociceptive signals but rather in the CNS mechanism underlying the establishment of chronic pain through nociplastic mechanisms ( Fehrenbacher et al, 2003 , Tanabe et al, 2008 ). In support of this, the appearance of the analgesic effect of PGB is latent in patients with chronic pain ( Carley et al, 2021 ). Such particularity of the PGB effect should be considered to understand the mechanism of its analgesic effect in animal models and human patients with persistent chronic pain.…”

“…Furthermore, the absence of the analgesic effect of PGB in mice with an α 2 δ 1 subunit variant lacking binding affinity to PGB has supported the notion that α 2 δ 1 subunit is the central target of gabapentinoid analgesics ( Field et al, 2006 , Patel and Dickenson, 2016 ). Notably, it is well established that PGB has a potent analgesic effect on chronic sustained pain while its effect on acute pain is limited ( Carley et al, 2021 ). This characteristic would imply that PGB might affect mechanisms involved not simply in the transmission of nociceptive signals but rather in the CNS mechanism underlying the establishment of chronic pain through nociplastic mechanisms ( Fehrenbacher et al, 2003 , Tanabe et al, 2008 ).…”

Preventing persistent postsurgical pain: A systematic review and component network meta‐analysis

“…Prevention of persistent postsurgical pain (PPP) is currently a priority for perioperative medicine (Glare et al, 2019;Katz et al, 2015;Kehlet et al, 2006). Evidence from randomized clinical trials (RCTs) suggests that perioperative pharmacological and regional anesthetic interventions may modestly reduce PPP risk (Carley et al, 2021;Weinstein et al, 2018). Since PPP is estimated to affect 10%-50% of the surgical population, even small-to-modest reductions in prevalence have the potential to improve the quality of life for many patients.…”