The efficacy of perioperative pregabalin treatment for preventing chronic pain remains a matter of debate. We searched the MEDLINE, EMBASE, LILACS, Cochrane, and Clinical Trial Register databases, and other sources, for randomized controlled trials comparing the effects of pregabalin and placebo. The primary outcome was the incidence of chronic postsurgical pain (CPSP) at 3 months. The secondary endpoints were CPSP at 3, 6, and 12 months and the incidence of chronic postsurgical neuropathic pain at the same time points. A random-effect meta-analysis was performed on the combined data. Evidence quality was rated by the GRADE method. We included 18 studies (2485 patients) in the meta-analysis. Overall, 60% of the trials reporting the primary outcome at 3 months were unpublished; the unpublished trials corresponded to 1492/1884 (79%) of the patients included in these studies. No difference in CPSP incidence between pregabalin and placebo was found at any time point; the risk ratio was 0.87 (0.66, 1.14), I2 5 57% at 3 months. The evidence was considered to be of moderate quality. Subgroup analysis by publication status, daily dose, type of administration, and type of surgery did not highlight any differences between subgroups. Insufficient data concerning the incidence of chronic postsurgical neuropathic pain were available for any firm recommendation to be made. Pooled data from published and unpublished studies provide no support for the efficacy of pregabalin for preventing CPSP.
BACKGROUND: Nonopioid adjuvant medications are increasingly included among perioperative Enhanced Recovery After Surgery protocols. Preoperative pregabalin has been shown to improve postoperative pain and limit reliance on opioid analgesia. Our group investigated the ability of preoperative pregabalin to also prevent postoperative nausea and vomiting (PONV). METHODS: Our group performed a meta-analysis of randomized trials that report outcomes on the effect of preoperative pregabalin on PONV endpoints in patients undergoing general anesthesia. RESULTS: Among all included trials (23 trials; n = 1693), preoperative pregabalin was associated with a significant reduction in PONV (risk ratio [RR] = 0.53; 95% confidence interval [CI], 0.39-0.73; P = 0.0001), nausea (RR = 0.62; 95% CI, 0.46-0.83; P = 0.002), and vomiting (RR = 0.68; 95% CI, 0.52-0.88; P = 0.003) at 24 hours. Subgroup analysis designed to account for major PONV confounders, including the exclusion trials with repeat dosing, thiopental induction, nitrous oxide maintenance, and prophylactic antiemetics and including high-risk surgery, resulted in similar antiemetic efficacy. Preoperative pregabalin is also associated with significantly increased rates of postoperative visual disturbance (RR = 3.11; 95% CI, 1.34-7.21; P = 0.008) compared with a control. CONCLUSIONS: Preoperative pregabalin is associated with significant reduction of PONV and should not only be considered as part of a multimodal approach to postoperative analgesia but also for prevention of PONV.
Evidence supporting postoperative pain management using pregabalin as an adjunct intervention across various surgical pain models is lacking. The objective of this systematic review was to evaluate "model-specific" comparative effectiveness and harms of pregabalin following a previously published systematic review protocol. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through August 2013. Data were screened and single extraction with independent verification and dual risk of bias assessment was performed. Quality of evidence (QoE) was rated using the GRADE approach. Primary outcomes were pain relief at rest and on movement and reduction in postoperative analgesic consumption. A total of 1423 records were screened, and 43 studies were included. Perioperative pregabalin resulted in: 16% (95% confidence interval [CI], 9%-21%) reduction in analgesic consumption (moderate QoE, 24 trials) and a small reduction in the magnitude of pain in surgeries associated with pronociceptive pain. Per 1000 patients, 10 more will experience blurred vision (95% CI, 5-20 more; moderate QoE, 17 trials) and 41 more sedation (95% CI, 13-77 more, 17 trials). To prevent 1 case of perioperative nausea and vomiting, the number needed to treat is 11 (95% CI: 7-28, 25 trials). Inadequate evidence addressed outcomes of enhanced recovery and serious harms. Pregabalin analgesic effectiveness is largely restricted to surgical procedures associated with pronociceptive mechanisms. The clinical significance of observed pregabalin benefits must be weighed against the uncertainties about serious harms and enhanced recovery to inform the careful selection of surgical patients. Recommendations for future research are proposed.
Summary We performed this systematic review to assess the analgesic efficacy of perioperative pregabalin. Subgroup analyses and meta-regression were performed to assess the impact of individual dose and frequency of pregabalin administration on analgesic efficacy. We included 55 studies. When all doses and administration regimens were combined, pregabalin was associated with a significant reduction in pain scores at rest and during movement and opioid consumption at 24 h compared with placebo {mean difference [95% confidence interval (CI)]=-0.38 (-0.57, -0.20), -0.47 (-0.76, -0.18), and -8.27 mg morphine equivalents (-10.08, -6.47), respectively}. Patients receiving pregabalin had less postoperative nausea and vomiting and pruritus compared with placebo [relative risk (RR) (95% CI)=0.62 (0.48, 0.80) and 0.49 (0.34, 0.70), respectively]. Sedation, dizziness, and visual disturbance were more common with pregabalin compared with placebo [RR (95% CI)=1.46 (1.08, 1.98), 1.33 (1.07, 1.64), and 3.52 (2.05, 6.04), respectively]. All doses of pregabalin tested (≤75, 100-150, and 300 mg) resulted in opioid sparing at 24 h after surgery. There were no significant differences in acute pain outcomes with pregabalin 100-300 mg between single preoperative dosing regimens and those including additional doses repeated after surgery. Data were insufficient to reach conclusions regarding persistent pain, but limited data available from two studies suggested that pregabalin might be effective for the reduction of neuropathic pain. In conclusion, this review suggests that pregabalin improves postoperative analgesia compared with placebo at the expense of increased sedation and visual disturbances.
The efficacy of pregabalin in acute postsurgical pain has been demonstrated in numerous studies; however, the analgesic efficacy and adverse effects of using pregabalin in various surgical procedures remain uncertain. We aim to assess the postsurgical analgesic efficacy and adverse events after pregabalin administration under different surgical categories using a systematic review and meta-analysis of randomized controlled trials.A search of the literature was performed between August 2014 to April 2015, using PubMed, Ovid via EMBASE, Google Scholar, and ClinicalTrials.gov with no limitation on publication year or language. Studies considered for inclusion were randomized controlled trials, reporting on relevant outcomes (2-, 24-hour pain scores, or 24 hour morphine-equivalent consumption) with treatment with perioperative pregabalin.Seventy-four studies were included. Pregabalin reduced pain scores at 2 hours in all categories: cardiothoracic (Hedge's g and 95%CI, -0.442 [-0.752 to -0.132], P = 0.005), ENT (Hedge g and 95%CI, -0.684 [-1.051 to -0.316], P < 0.0001), gynecologic (Hedge g, 95%CI, -0.792 [-1.235 to -0.350], P < 0.0001), laparoscopic cholecystectomy (Hedge g, 95%CI, -0.600 [-0.989 to -0.210], P = 0.003), orthopedic (Hedge g, 95%CI, -0.507 [-0.812 to -0.202], P = 0.001), spine (Hedge g, 95%CI, -0.972 [-1.537 to -0.407], P = 0.001), and miscellaneous procedures (Hedge g, 95%CI, -1.976 [-2.654 to -1.297], P < 0.0001). Pregabalin reduced 24-hour morphine consumption in gynecologic (Hedge g, 95%CI, -1.085 [-1.582 to -0.441], P = 0.001), laparoscopic cholecystectomy (Hedge g, 95%CI, -0.886 [-1.652 to -0.120], P = 0.023), orthopedic (Hedge g, 95%CI, -0.720 [-1.118 to -0.323], P < 0.0001), spine (Hedge g, 95%CI, -1.016 [-1.732 to -0.300], P = 0.005), and miscellaneous procedures (Hedge g, 95%CI, -1.329 [-2.286 to -0.372], P = 0.006). Pregabalin resulted in significant sedation in all surgical categories except ENT, laparoscopic cholecystectomy, and gynecologic procedures. Postoperative nausea and vomiting was only significant after pregabalin in miscellaneous procedures.Analgesic effects and incidence of adverse effects of using pregabalin are not equal in different surgical categories.
Multimodal treatment of postoperative pain using adjuncts such as gabapentin is becoming more common. Pregabalin has anti-hyperalgesic properties similar to gabapentin. In this systematic review, we evaluated randomized, controlled trials (RCTs) for the analgesic efficacy and opioid-sparing effect of pregabalin in acute postoperative pain. A systematic search of Medline (1966-2010), the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was performed. We identified 11 valid RCTs that used pregabalin for acute postoperative pain. Postoperative pain intensity was not reduced by pregabalin. Cumulative opioid consumption at 24 h was significantly decreased with pregabalin. At pregabalin doses of <300 mg, there was a reduction of 8.8 mg [weighted mean difference (WMD)]. At pregabalin doses ≥300 mg, cumulative opioid consumption was even lower (WMD, -13.4 mg). Pregabalin reduced opioid-related adverse effects such as vomiting [risk ratio (RR) 0.73; 95% confidence interval (CI) 0.56-0.95]. However, the risk of visual disturbance was greater (RR 3.29; 95% CI 1.95-5.57). Perioperative pregabalin administration reduced opioid consumption and opioid-related adverse effects after surgery.
OBJECTIVE: Perioperative gabapentine administration improves analgesia, reduces postoperative nausea and vomiting, but increases sedation. Pregabalin is also a gabapentinoid, with an improved bioavailability. This systematic review evaluates the analgesic effect and tolerance of perioperative pregabaline.
STUDY DESIGN: Systematic review.
METHODS: Systematic search in Pubmed database of clinical human randomized controlled studies dealing with perioperative administration of pregabalin. A quantitative review of pregabalin efficiency and an analysis of the main side effects reported in these studies was then performed.
RESULTS: Twenty-three study arms (884 patients) received at least one dose of pregabalin in 17 studies (totalizing 1577 patients). Pregabalin improved analgesia in 11 of 23 study arms. Pregabalin improved analgesia in three of 12 study arms after ambulatory surgery, and in eight of 11 after major surgery (P=0.04). Two of three studies about chronic postoperative pain revealed improved results in pregabalin groups. Nevertheless, pregabalin did not reduce postoperative nausea/vomiting, pruritus and headache, but increased trouble with vision, drowsiness, severe sedation and dizziness during the first postoperative hours, without severe clinical consequence. Severe sedation seemed clearly dose dependant, while drowsiness, dizziness or visual disturbance did not.
CONCLUSION: A favorable benefit risk-ratio is demonstrated only for major surgery (excluding ambulatory surgery). The lack of data concerning tolerance of pregabalin in the elderly and/or in case of renal dysfunction forbids any conclusion in these populations.
