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.
OBJECTIVE: To update a systematic review of published research on pharmacotherapy for pain post-spinal cord injury (SCI).
DATA SOURCES: PubMed/MEDLINE, CINAHL, Embase, and PsycINFO databases were searched for articles from 2009 to September 2015 examining treatment of pain post-SCI.
STUDY SELECTION: Studies were included for analysis if they met the following 4 a priori criteria: (1) written in the English language; (2) ≥50% of subjects had an SCI, unless results were stratified by population type; (3) participants included ≥3 subjects with an SCI; and (4) any intervention involving pharmacologic treatment for the improvement of pain.
DATA EXTRACTION: Randomized controlled trials were assessed for methodologic quality using the Physiotherapy Evidence Database scoring system. All research designs were given a level of evidence according to a modified Sackett Scale.
DATA SYNTHESIS: Seven new studies met our inclusion criteria. The new studies fell into the following categories: analgesics (n=1), anticonvulsants (n=2), antidepressants (n=2), antispastics (n=1), and cannabinoids (n=1). There was evidence for 5 new pharmacotherapies among the SCI population; these included the following: oxycodone, duloxetine, venlafaxine, phenol block, and dronabinol. Levels of evidence for all therapy modalities were updated based on the new evidence.
CONCLUSIONS: Anticonvulsants remain the most studied and supported pharmacotherapy for neuropathic pain post-SCI. Antidepressants showed reduction in pain only among those with comorbid depression. Botulinum toxin and phenol blocks were supported for the reduction of mixed pain post-SCI.
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.
BACKGROUND: Pregabalin has been used as an adjuvant in some trials to control postoperative pain after gynecologic surgery. However, the potential clinical advantage remains debatable. OBJECTIVE: We performed a meta-analysis of clinical trials of pregabalin to evaluate its ability to control acute postoperative pain after gynecologic surgery. METHODS: We searched PubMed, ScienceDiret, and the Cochrane Library of Randomized Controlled Trials up to January 2014. We performed a systematic review and meta-analysis of prospective controlled studies reporting pregabalin for gynecologic surgery. The primary outcome was pain outcomes and postoperative cumulative opioid consumption. Data were reported as weighted mean differences (WMDs) and 95% CIs. The secondary outcome was adverse effects after surgery. RESULTS: Six valid randomized trials met the eligibility criteria and were included in the meta-analysis. Pooled data were collected from 452 patients between 2007 and 2012 (These trials were separately conducted in Greece 2012, India 2011-2012, Turkey 2011, Denmark 2009 and Australia 2007). The pregabalin-treated patients consumed fewer opioids during the first 24 hours post-operatively (WMD, -8.50 mg; 95% CI, -11.29 to -5.71 mg; P o 0.00001). Pain intensity at rest and on movement or coughing revealed a statistically significant pain relief effect of pregabalin during 24 hours post-operatively (at rest: WMD, -6.20 mm; 95% CI, -- 11.83 to --0.58 mm; P -- 0.03; on movement or coughing: WMD, -5.32 mm; 95% CI, -9.73 to -0.91 mm; P -- 0.02). No differences were found between the pregabalin and control groups for the adverse effects. CONCLUSIONS: Pregabalin has an analgesic and opioid-sparing effect and does not increase the frequency of adverse effects in acute postoperative pain management after gynecologic surgery.
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.
BACKGROUND: New drug treatments, clinical trials, and standards of quality for assessment of evidence justify an update of evidence-based recommendations for the pharmacological treatment of neuropathic pain. Using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), we revised the Special Interest Group on Neuropathic Pain (NeuPSIG) recommendations for the pharmacotherapy of neuropathic pain based on the results of a systematic review and meta-analysis.
METHODS: Between April, 2013, and January, 2014, NeuPSIG of the International Association for the Study of Pain did a systematic review and meta-analysis of randomised, double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including studies published in peer-reviewed journals since January, 1966, and unpublished trials retrieved from ClinicalTrials.gov and websites of pharmaceutical companies. We used number needed to treat (NNT) for 50% pain relief as a primary measure and assessed publication bias; NNT was calculated with the fixed-effects Mantel-Haenszel method.
FINDINGS: 229 studies were included in the meta-analysis. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-reviewed journals reported greater effects than did unpublished studies (r(2) 9·3%, p=0·009). Trial outcomes were generally modest: in particular, combined NNTs were 6·4 (95% CI 5·2-8·4) for serotonin-noradrenaline reuptake inhibitors, mainly including duloxetine (nine of 14 studies); 7·7 (6·5-9·4) for pregabalin; 7·2 (5·9-9·21) for gabapentin, including gabapentin extended release and enacarbil; and 10·6 (7·4-19·0) for capsaicin high-concentration patches. NNTs were lower for tricyclic antidepressants, strong opioids, tramadol, and botulinum toxin A, and undetermined for lidocaine patches. Based on GRADE, final quality of evidence was moderate or high for all treatments apart from lidocaine patches; tolerability and safety, and values and preferences were higher for topical drugs; and cost was lower for tricyclic antidepressants and tramadol. These findings permitted a strong recommendation for use and proposal as first-line treatment in neuropathic pain for tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, pregabalin, and gabapentin; a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin high-concentration patches, and tramadol; and a weak recommendation for use and proposal as third line for strong opioids and botulinum toxin A. Topical agents and botulinum toxin A are recommended for peripheral neuropathic pain only.
INTERPRETATION: Our results support a revision of the NeuPSIG recommendations for the pharmacotherapy of neuropathic pain. Inadequate response to drug treatments constitutes a substantial unmet need in patients with neuropathic pain. Modest efficacy, large placebo responses, heterogeneous diagnostic criteria, and poor phenotypic profiling probably account for moderate trial outcomes and should be taken into account in future studies.
FUNDING: NeuPSIG of the International Association for the Study of Pain.
BACKGROUND: Multiple treatments for painful diabetic peripheral neuropathy are available. PURPOSE: To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy. DATA SOURCES: Multiple electronic databases between January 2007 and April 2014, without language restriction. STUDY SELECTION: Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy. DATA EXTRACTION: Duplicate extraction of study data and assessment of risk of bias. DATA SYNTHESIS: 65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin-norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], -0.34 [95% credible interval {CrI}, -0.63 to -0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, -1.36 [CrI, -1.77 to -0.95]), topical capsaicin (SMD, -0.91 [CrI, -1.18 to -0.08]), TCAs (SMD, -0.78 [CrI, -1.24 to -0.33]), and anticonvulsants (SMD, -0.67 [CrI, -0.97 to -0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, -1.57 [CrI, -2.83 to -0.31]), venlafaxine (SMD, -1.53 [CrI, -2.41 to -0.65]), duloxetine (SMD, -1.33 [CrI, -1.82 to -0.86]), and amitriptyline (SMD, -0.72 [CrI, -1.35 to -0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin. LIMITATION: Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (<=3 months) follow-up and unclear or high risk of bias. CONCLUSION: Several medications may be effective for short-term management of painful diabetic neuropathy, although their comparative effectiveness is unclear. PRIMARY FUNDING SOURCE: Mayo Foundation for Medical Education and Research.
BACKGROUND: While laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day-surgery and overnight stay following laparoscopic cholecystectomy. The safety and effectiveness of different pharmacological interventions such as non-steroidal anti-inflammatory drugs, opioids, and anticonvulsant analgesics in people undergoing laparoscopic cholecystectomy is unknown.
OBJECTIVES: To assess the benefits and harms of different analgesics in people undergoing laparoscopic cholecystectomy.
SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization International Clinical Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify randomised clinical trials of relevance to this review.
SELECTION CRITERIA: We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different pharmacological interventions with no intervention or inactive controls for outcomes related to benefit in this review. We considered comparative non-randomised studies with regards to treatment-related harms. We also considered trials that compared one class of drug with another class of drug for this review.
DATA COLLECTION AND ANALYSIS: Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI).
MAIN RESULTS: We included 25 trials with 2505 participants randomised to the different pharmacological agents and inactive controls. All the trials were at unclear risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Participants were allowed to take additional analgesics as required in 24 of the trials. The pharmacological interventions in all the included trials were aimed at preventing pain after laparoscopic cholecystectomy. There were considerable differences in the pharmacological agents used and the methods of administration. The estimated effects of the intervention on the proportion of participants who were discharged as day-surgery, the length of hospital stay, or the time taken to return to work were imprecise in all the comparisons in which these outcomes were reported (very low quality evidence). There was no mortality in any of the groups in the two trials that reported mortality (183 participants, very low quality evidence). Differences in serious morbidity outcomes between the groups were imprecise across all the comparisons (very low quality evidence). None of the trials reported patient quality of life or time taken to return to normal activity. The pain at 4 to 8 hours was generally reduced by about 1 to 2 cm on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). The pain at 9 to 24 hours was generally reduced by about 0.5 cm (a modest reduction) on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence).
AUTHORS' CONCLUSIONS: There is evidence of very low quality that different pharmacological agents including non-steroidal anti-inflammatory drugs, opioid analgesics, and anticonvulsant analgesics reduce pain scores in people at low anaesthetic risk undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.
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.
