Gabapentinoids
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Database: Ovid MEDLINE(R) ALL <1946 to June 19, 2024> Search Strategy:
1 Gabapentin/ (4531) 2 Pregabalin/ (2569) 3 Gabapentinoids.mp. (804) 4 1 or 2 or 3 (7109) 5 Pain, Postoperative/ (50517) 6 4 and 5 (704) 7 limit 6 to (meta analysis or multicenter study or randomized controlled trial or "systematic review") (374) 8 limit 7 to last 5 years (121) 9 limit 8 to (humans and "all adult (19 plus years)") (51) 10 from 9 keep 3,5-6,8,10-11,19,22,29,32,34,36-38,45 (15) 11 from 10 keep 1-2,4-5,8,10,13-15 (9)
Source
JAMA Network Open. 6(8):e2328121, 2023 08 01.
Authors
Tsai SHL; Hu CW; El Sammak S; Durrani S; Ghaith AK; Lin CCJ; Krzyz EZ; Bydon M; Fu TS; Lin TY
Abstract
IMPORTANCE: Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not been well established.
OBJECTIVE: To evaluate the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery.
DATA SOURCES: PubMed/MEDLINE, Embase, Web of Science, Cochrane library, and Scopus databases were searched for articles until August 7, 2021.
STUDY SELECTION: Randomized clinical trials conducted among patients who received pregabalin or gabapentin while undergoing spine surgery were included.
DATA EXTRACTION AND SYNTHESIS: Two investigators independently performed data extraction following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guideline. The network meta-analysis was conducted from August 2022 to February 2023 using a random-effects model.
MAIN OUTCOMES AND MEASURES: The primary outcome was pain intensity measured using the Visual Analog Scale (VAS), and secondary outcomes included opioid consumption and adverse events.
RESULTS: Twenty-seven randomized clinical trials with 1861 patients (median age, 45.99 years [range, 20.00-70.00 years]; 759 women [40.8%]) were included in the systematic review and network meta-analysis. Compared with placebo, the VAS pain score was lowest with gabapentin 900 mg per day, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. Additionally, gabapentin 900 mg per day was found to be associated with the lowest opioid consumption among all dosages of gabapentin and pregabalin, with a mean difference of -22.07% (95% CI, -33.22% to -10.92%) for the surface under the cumulative ranking curve compared with placebo. There was no statistically significant difference in adverse events (nausea, vomiting, and dizziness) among all treatments. No substantial inconsistency between direct and indirect evidence was detected for all outcomes.
CONCLUSIONS AND RELEVANCE: These findings suggest that gabapentin 900 mg per day before spine surgery is associated with the lowest VAS pain score among all dosages. In addition, no differences in adverse events were noted among all treatments.
Publication Type
Meta-Analysis. Systematic Review. Journal Article.
Source
Journal of Cardiothoracic & Vascular Anesthesia. 37(7):1169-1178, 2023 07.
Authors
Heybati K; Zhou F; Lynn MJ; Deng J; Ali S; Hou W; Heybati S; Tzanis K; Krever M; Mughal R; Ramakrishna H
Abstract
OBJECTIVES: To compare the relative efficacy of adjuvant nonopioid analgesic regimens in adult cardiac surgical patients.
DESIGN: This frequentist, random-effects network meta-analysis (NMA) was prospectively registered on PROSPERO (CRD42021282913) and conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA). The risk of bias (RoB) and confidence of evidence were assessed by RoB 2 and Confidence in Network Meta-Analysis, respectively. Relevant databases were searched from inception to October 9, 2021.
SETTING: A total of 124 (N = 26,257) randomized controlled trials were included, of which 110 were analyzed.
PARTICIPANTS: Trials enrolling adults (>=18 years of age) undergoing cardiac surgery that compared nonopioid analgesics against other nonopioid analgesics, placebo, or no additional treatment, as adjuvants to standard analgesic management, and reported at least 1 of the outcomes of interest.
MEASUREMENT AND MAIN RESULTS: Outcomes of interest included resting postoperative pain scores at 24 hours. Compared with standard care and/or placebo, pain scores were reduced significantly by 10 different regimens, including acetaminophen (N = 176; mean difference [MD] -0.66 points, 95% CI -1.16 to -0.15 points; high confidence), magnesium (N = 323; -0.05 points, 95% CI -0.07 to -0.02 points; high confidence), gabapentin (N = 96; MD -0.40 points, 95% CI -0.71 to -0.09; moderate confidence), and clonidine (N = 64; MD v0.38 points, 95% CI -0.73 to v0.04 points; moderate confidence). Indomethacin, diclofenac, magnesium, and gabapentin significantly reduced 24-hour opioid consumption. Four regimens significantly decreased the intensive care unit length of stay. Hydrocortisone, dexmedetomidine, and clonidine significantly decreased the duration of mechanical ventilation. Magnesium decreased, while methylprednisolone significantly increased, the risk of myocardial infarction.
CONCLUSIONS: Given the increasing emphasis on enhanced recovery after surgery(ERAS) protocols and the eventual goal of limiting opiate prescriptions postoperatively, the authors' data suggested far greater use of nonopioid adjuncts to minimize pain and enhance recovery following cardiac surgery. Copyright © 2023 Elsevier Inc. All rights reserved.
Publication Type
Meta-Analysis. Journal Article.
Source
BMC Anesthesiology. 22(1):318, 2022 10 15.
Authors
Jouybar R; Kazemifar S; Asmarian N; Karami A; Khademi S
Abstract
BACKGROUND: This study aimed to compare the effects of melatonin, dexmedetomidine, and gabapentin on postoperative pain and anxiety following laminectomy.
METHODS: In this randomized clinical trial, 99 patients aged 40-60 years old with American Society of Anesthesiologists physical status I-II undergoing laminectomy were divided into three groups receiving 600mg gabapentin (group G), 10mg melatonin (group M), or starch tablets (group D). The Hospital Anxiety and Depression Scale (HADS) was used to measure postoperative anxiety while a Visual Analogue Scale (VAS) was employed to measure pain severity. Patients' satisfaction with pain treatment was also measured together with the frequency of nausea and vomiting.
RESULTS: The postoperative HADS decreased in all groups over time. Time and group had no significant interaction effect on the HADS score. Patients in the melatonin group had lower HADS at 2 and 6h after surgery. According to the VAS, the groups significantly differed in pain scores 6 and 24h after surgery. Lower VAS scores were observed 6h after surgery in the dexmedetomidine group compared with the gabapentin group and 24h after surgery in the dexmedetomidine group compared with the gabapentin and melatonin groups. Narcotic requirements, patients' satisfaction, and vital sign changes did not significantly vary among the groups. Notably, patients in the melatonin group had less nausea and vomiting.
TRIAL REGISTRATION: This study was registered in the Iranian Registry of Clinical Trials (No. IRCT20141009019470N82, 29.06.2019) where the trial protocol could be accessed.
CONCLUSION: Melatonin is effective as a postoperative anti-anxiety drug. Dexmedetomidine is useful in reducing postoperative pain. Copyright © 2022. The Author(s).
Publication Type
Journal Article. Randomized Controlled Trial. Research Support, Non-U.S. Gov't.
Nonopioid Analgesics for the Perioperative Geriatric Patient: A Narrative Review.
Source
Anesthesia & Analgesia. 135(2):290-306, 2022 08 01.
Authors
Wilson SH; Wilson PR; Bridges KH; Bell LH; Clark CA
Abstract
Management of acute perioperative pain in the geriatric patient can be challenging as the physiologic and pharmacokinetic changes associated with aging may predispose older patients to opioid-related side effects. Furthermore, elderly adults are more susceptible to postoperative delirium and postoperative cognitive dysfunction, which may be exacerbated by both poorly controlled postoperative pain and commonly used pain medications. This narrative review summarizes the literature published in the past 10 years for several nonopioid analgesics commonly prescribed to the geriatric patient in the perioperative period. Nonopioid analgesics are broken down as follows: medications prescribed throughout the perioperative period (acetaminophen and nonsteroidal anti-inflammatory drugs), medications limited to the acute perioperative setting ( N -methyl-D-aspartate receptor antagonists, dexmedetomidine, dexamethasone, and local anesthetics), and medications to be used with caution in the geriatric patient population (gabapentinoids and muscle relaxants). Our search identified 1757 citations, but only 33 specifically focused on geriatric analgesia. Of these, only 21 were randomized clinical trials' and 1 was a systematic review. While guidance in tailoring pain regimens that focus on the use of nonopioid medications in the geriatric patient is lacking, we summarize the current literature and highlight that some nonopioid medications may extend benefits to the geriatric patient beyond analgesia. Copyright © 2022 International Anesthesia Research Society.
Publication Type
Journal Article. Systematic Review.
Multimodal Analgesic Regimen for Spine Surgery: A Randomized Placebo-controlled Trial.
Source
Anesthesiology. 132(5):992-1002, 2020 05.
Authors
Maheshwari K; Avitsian R; Sessler DI; Makarova N; Tanios M; Raza S; Traul D; Rajan S; Manlapaz M; Machado S; Krishnaney A; Machado A; Rosenquist R; Kurz A
Abstract
BACKGROUND: Various multimodal analgesic approaches have been proposed for spine surgery. The authors evaluated the effect of using a combination of four nonopioid analgesics versus placebo on Quality of Recovery, postoperative opioid consumption, and pain scores.
METHODS: Adults having multilevel spine surgery who were at high risk for postoperative pain were double-blind randomized to placebos or the combination of single preoperative oral doses of acetaminophen 1,000 mg and gabapentin 600 mg, an infusion of ketamine 5 microg/kg/min throughout surgery, and an infusion of lidocaine 1.5 mg/kg/h intraoperatively and during the initial hour of recovery. Postoperative analgesia included acetaminophen, gabapentin, and opioids. The primary outcome was the Quality of Recovery 15-questionnaire (0 to 150 points, with 15% considered to be a clinically important difference) assessed on the third postoperative day. Secondary outcomes were opioid use in morphine equivalents (with 20% considered to be a clinically important change) and verbal-response pain scores (0 to 10, with a 1-point change considered important) over the initial postoperative 48 h.
RESULTS: The trial was stopped early for futility per a priori guidelines. The average duration +/- SD of surgery was 5.4 +/- 2.1 h. The mean +/- SD Quality of Recovery score was 109 +/- 25 in the pathway patients (n = 150) versus 109 +/- 23 in the placebo group (n = 149); estimated difference in means was 0 (95% CI, -6 to 6, P = 0.920). Pain management within the initial 48 postoperative hours was not superior in analgesic pathway group: 48-h opioid consumption median (Q1, Q3) was 72 (48, 113) mg in the analgesic pathway group and 75 (50, 152) mg in the placebo group, with the difference in medians being -9 (97.5% CI, -23 to 5, P = 0.175) mg. Mean 48-h pain scores were 4.8 +/- 1.8 in the analgesic pathway group versus 5.2 +/- 1.9 in the placebo group, with the difference in means being -0.4 (97.5% CI; -0.8, 0.1, P = 0.094).
CONCLUSIONS: An analgesic pathway based on preoperative acetaminophen and gabapentin, combined with intraoperative infusions of lidocaine and ketamine, did not improve recovery in patients who had multilevel spine surgery.
Publication Type
Journal Article. Randomized Controlled Trial. Research Support, Non-U.S. Gov't.
Source
Anesthesiology. 131(1):119-131, 2019 07.
Authors
Anwar S; Cooper J; Rahman J; Sharma C; Langford R
Abstract
BACKGROUND: Persistent postsurgical pain is common and affects quality of life. The hypothesis was that use of pregabalin and ketamine would prevent persistent pain after cardiac surgery.
METHODS: This randomized, double-blind, placebo-controlled trial was undertaken at two cardiac surgery centers in the United Kingdom. Adults without chronic pain and undergoing any elective cardiac surgery patients via sternotomy were randomly assigned to receive either usual care, pregabalin (150 mg preoperatively and twice daily for 14 postoperative days) alone, or pregabalin in combination with a 48-h postoperative infusion of intravenous ketamine at 0.1 mg . kg . h. The primary endpoints were prevalence of clinically significant pain at 3 and 6 months after surgery, defined as a pain score on the numeric rating scale of 4 or higher (out of 10) after a functional assessment of three maximal coughs. The secondary outcomes included acute pain, opioid use, and safety measures, as well as long-term neuropathic pain, analgesic requirement, and quality of life.
RESULTS: In total, 150 patients were randomized, with 17 withdrawals from treatment and 2 losses to follow-up but with data analyzed for all participants on an intention-to-treat basis. The prevalence of pain was lower at 3 postoperative months for pregabalin alone (6% [3 of 50]) and in combination with ketamine (2% [1 of 50]) compared to the control group (34% [17 of 50]; odds ratio = 0.126 [0.022 to 0.5], P = 0.0008; and 0.041 [0.0009 to 0.28], P < 0.0001, respectively) and at 6 months for pregabalin alone (6% [3 of 50]) and in combination with ketamine 0% (0 of 5) compared to the control group (28% [14 of 50]; odds ratio = 0.167 [0.029 to 0.7], P = 0.006; and 0.000 [0 to 0.24], P < 0.0001). Diplopia was more common in both active arms.
CONCLUSIONS: Preoperative administration of 150 mg of pregabalin and postoperative continuation twice daily for 14 days significantly lowered the prevalence of persistent pain after cardiac surgery.
Publication Type
Journal Article. Randomized Controlled Trial. Research Support, Non-U.S. Gov't.
Source
Journal of Pain. 20(8):980-993, 2019 08.
Authors
Khan JS; Hodgson N; Choi S; Reid S; Paul JE; Hong NJL; Holloway C; Busse JW; Gilron I; Buckley DN; McGillion M; Clarke H; Katz J; Mackey S; Avram R; Pohl K; Rao-Melacini P; Devereaux PJ
Abstract
Persistent postsurgical pain is defined as pain localized to the area of surgery of a duration of >=2 months and is, unfortunately, a common complication after breast cancer surgery. Although there is insufficient evidence to support any preventative strategy, prior literature suggests the possible efficacy of intravenous lidocaine and perioperative pregabalin in preventing persistent pain after surgery. To determine feasibility of conducting a larger definitive trial, we conducted a multicenter 2x2 factorial, randomized, placebo-controlled pilot trial of 100 female patients undergoing breast cancer surgery. Patients were randomized to receive an intraoperative lidocaine infusion (1.5 mg/kg bolus followed by 2 mg/kg/h) or placebo and perioperative pregabalin (300 mg preoperatively, 75 mg twice daily for 9 days) or placebo. All feasibility criteria were surpassed; recruitment of 100 patients was accomplished within 42 weeks, with a follow-up rate of 100% and study drug compliance of >=80%. At 3 months, 53% of patients reported persistent neuropathic pain. Although there was no interaction between lidocaine and pregabalin, lidocaine decreased the development of persistent neuropathic pain (43.1% vs 63.3%; relative risk=.68; 95% confidence interval=.47-1.0). Pregabalin did not reduce persistent pain (60% vs 46%; relative risk=1.3; 95% confidence interval=.90-1.90) and neither pregabalin nor lidocaine impacted acute postoperative pain, opioid consumption, pain interference, or quality of life. Our pilot trial successfully demonstrated feasibility and provided promising data for conducting further trials of intraoperative lidocaine infusions during breast cancer surgeries. Clinical trial number: NCT02240199 PERSPECTIVE: This article reports the findings of a pilot randomized, controlled trial evaluating the effects of perioperative pregabalin and intraoperative lidocaine infusions in patients undergoing breast cancer surgery. This trial demonstrated the feasibility of conducting a larger trial and provided promising data that these interventions may decrease the development of persistent pain. Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.
Publication Type
Journal Article. Multicenter Study. Randomized Controlled Trial. Research Support, Non-U.S. Gov't.
Source
JAMA Network Open. 2(3):e190168, 2019 03 01.
Authors
Hah JM; Cramer E; Hilmoe H; Schmidt P; McCue R; Trafton J; Clay D; Sharifzadeh Y; Ruchelli G; Goodman S; Huddleston J; Maloney WJ; Dirbas FM; Shrager J; Costouros JG; Curtin C; Mackey SC; Carroll I
Abstract
Importance: Acute postoperative pain is associated with the development of persistent postsurgical pain, but it is unclear which aspect is most estimable.
Objective: To identify patient clusters based on acute pain trajectories, preoperative psychosocial characteristics associated with the high-risk cluster, and the best acute pain predictor of remote outcomes.
Design, Setting, and Participants: A secondary analysis of the Stanford Accelerated Recovery Trial randomized, double-blind clinical trial was conducted at a single-center, tertiary, referral teaching hospital. A total of 422 participants scheduled for thoracotomy, video-assisted thoracoscopic surgery, total hip replacement, total knee replacement, mastectomy, breast lumpectomy, hand surgery, carpal tunnel surgery, knee arthroscopy, shoulder arthroplasty, or shoulder arthroscopy were enrolled between May 25, 2010, and July 25, 2014. Data analysis was performed from January 1 to August 1, 2018.
Interventions: Patients were randomized to receive gabapentin (1200 mg, preoperatively, and 600 mg, 3 times a day postoperatively) or active placebo (lorazepam, 0.5 mg preoperatively, inactive placebo postoperatively) for 72 hours.
Main Outcomes and Measures: A modified Brief Pain Inventory prospectively captured 3 surgical site pain outcomes: average pain and worst pain intensity over the past 24 hours, and current pain intensity. Within each category, acute pain trajectories (first 10 postoperative pain scores) were compared using a k-means clustering algorithm. Fifteen descriptors of acute pain were compared as predictors of remote postoperative pain resolution, opioid cessation, and full recovery.
Results: Of the 422 patients enrolled, 371 patients (<=10% missing pain scores) were included in the analysis. Of these, 146 (39.4%) were men; mean (SD) age was 56.67 (11.70) years. Two clusters were identified within each trajectory category. The high pain cluster of the average pain trajectory significantly predicted prolonged pain (hazard ratio [HR], 0.63; 95% CI, 0.50-0.80; P < .001) and delayed opioid cessation (HR, 0.52; 95% CI, 0.41-0.67; P < .001) but was not a predictor of time to recovery in Cox proportional hazards regression (HR, 0.89; 95% CI, 0.69-1.14; P = .89). Preoperative risk factors for categorization to the high average pain cluster included female sex (adjusted relative risk [ARR], 1.36; 95% CI, 1.08-1.70; P = .008), elevated preoperative pain (ARR, 1.11; 95% CI, 1.07-1.15; P < .001), a history of alcohol or drug abuse treatment (ARR, 1.90; 95% CI, 1.42-2.53; P < .001), and receiving active placebo (ARR, 1.27; 95% CI, 1.03-1.56; P = .03). Worst pain reported on postoperative day 10 was the best predictor of time to pain resolution (HR, 0.83; 95% CI, 0.78-0.87; P < .001), opioid cessation (HR, 0.84; 95% CI, 0.80-0.89; P < .001), and complete surgical recovery (HR, 0.91; 95% CI, 0.86-0.96; P < .001).
Conclusions and Relevance: This study has shown a possible uniform predictor of remote postoperative pain, opioid use, and recovery that can be easily assessed. Future work is needed to replicate these findings.
Trial Registration: ClinicalTrials.gov Identifier: NCT01067144.
Publication Type
Journal Article. Randomized Controlled Trial. Research Support, N.I.H., Extramural. Research Support, Non-U.S. Gov't.
Source
Anesthesiology. 130(1):63-71, 2019 01.
Authors
Myhre M; Jacobsen HB; Andersson S; Stubhaug A
Abstract
BACKGROUND: Pregabalin has shown opioid sparing and analgesic effects in the early postoperative period; however, perioperative effects on cognition have not been studied. A randomized, parallel group, placebo-controlled investigation in 80 donor nephrectomy patients was previously performed that evaluated the analgesic, opioid-sparing, and antihyperalgesic effects of pregabalin. This article describes a secondary exploratory analysis that tested the hypothesis that pregabalin would impair cognitive function compared to placebo.
METHODS: Eighty patients scheduled for donor nephrectomy participated in this randomized, placebo-controlled study. Pregabalin (150 mg twice daily, n = 40) or placebo (n = 40) was administered on the day of surgery and the first postoperative day, in addition to a pain regimen consisting of opioids, steroids, local anesthetics, and acetaminophen. Specific cognitive tests measuring inhibition, sustained attention, psychomotor speed, visual memory, and strategy were performed at baseline, 24 h, and 3 to 5 days after surgery, using tests from the Cambridge Neuropsychological Test Automated Battery.
RESULTS: In the spatial working memory within errors test, the number of errors increased with pregabalin compared to placebo 24 h after surgery; median (25th, 75th percentile) values were 1 (0, 6) versus 0 (0, 1; rate ratio [95% CI], 3.20 [1.55 to 6.62]; P = 0.002). Furthermore, pregabalin significantly increased the number of errors in the stop-signal task stop-go test compared with placebo; median (25th, 75th percentile) values were 3 (1, 6) versus 1 (0, 2; rate ratio, 2.14 [1.13 to 4.07]; P = 0.020). There were no significant differences between groups in the paired associated learning, reaction time, rapid visual processing, or spatial working memory strategy tests.
CONCLUSIONS: Perioperative pregabalin significantly negatively affected subdomains of executive functioning, including inhibition, and working memory compared to placebo, whereas psychomotor speed was not changed.
Publication Type
Journal Article. Randomized Controlled Trial. Research Support, Non-U.S. Gov't.