Efficacy of flupirtine for postoperative pain: A systematic review and meta-analysis

Background and Aims: Flupirtine has been used for various chronic pain conditions, but its utility in the perioperative period as an analgesic is still inconclusive. This systematic review and meta-analysis aimed to assess the efficacy of flupirtine for postoperative pain. Methods: PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) were explored for the randomised controlled trials (RCTs) which compared flupirtine with other analgesic/placebo for perioperative pain in adult patients undergoing surgery. The standardised mean difference (SMD) of pain scores, the need for rescue analgesia and all adverse effects were assessed. Heterogeneity was assessed using Cochrane's Q statistic test and I2 statistic. Cochrane Collaboration's tool was used to evaluate the risk of bias and the quality of the RCTs. Results: A total of 13 RCTs (including 1,014 patients) that evaluated the use of flupirtine for postoperative pain were included in the study. The pooled SMD of postoperative pain scores revealed that flupirtine and other analgesics were comparable at 0, 6, 12 and 24 hours (P > 0.05), while at 48 hours, flupirtine showed poor pain control (P = 0.04) as compared to other analgesics. There were no significant differences at other time points and on comparison of flupirtine with placebo. The side effect profile was comparable between flupirtine and other analgesics. Conclusion: The current evidence suggests that perioperative flupirtine was not superior to other most commonly used analgesics and placebo for the treatment of postoperative pain.

[1]  D. Thiyagarajan,et al.  Opioid-free anaesthesia for laparoscopic surgeries - A prospective non-randomised study in a tertiary care hospital , 2022, Indian journal of anaesthesia.

[2]  P. Navalesi,et al.  Trial sequential analysis: plain and simple , 2020, Korean journal of anesthesiology.

[3]  S. Mishra,et al.  Time course of psychomotor recovery after intravenous dexmedetomidine infusion as a part of balanced anaesthetic technique: A randomised, double-blind study , 2019, Indian journal of anaesthesia.

[4]  L. Radbruch,et al.  Systematic review and meta‐analysis on non‐opioid analgesics in palliative medicine , 2018, Journal of cachexia, sarcopenia and muscle.

[5]  Abhijit S. Nair.  Flupirtine: A Less-Explored, Neglected Nonopioid Analgesic. , 2018, Anesthesia and analgesia.

[6]  Sowmya Chinnaiyan,et al.  A comparative study of efficacy and safety of flupirtine versus piroxicam in postoperative pain in patients undergoing lower limb surgery , 2017, Journal of pain research.

[7]  Hossam M. Hammady,et al.  Rayyan—a web and mobile app for systematic reviews , 2016, Systematic Reviews.

[8]  V. Ahuja,et al.  Effect of preoperative flupirtine on postoperative morphine sparing in patients undergoing total abdominal hysterectomy , 2016, Saudi journal of anaesthesia.

[9]  S. Mitra,et al.  Comparison of analgesic efficacy of flupirtine maleate and ibuprofen in gynaecological ambulatory surgeries: A randomized controlled trial , 2015, Indian journal of anaesthesia.

[10]  G. Yadav,et al.  Role of flupirtine as a preemptive analgesic in patients undergoing laparoscopic cholecystectomy , 2015, Journal of anaesthesiology, clinical pharmacology.

[11]  Jiming Liu,et al.  Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range , 2014, BMC Medical Research Methodology.

[12]  Lal D. Mishra,et al.  Evaluating the Role of Flupirtine for Postcraniotomy Pain and Compare it With Diclofenac Sodium: A Prospective, Randomized, Double Blind, Placebo-controlled Study , 2014, Journal of neurosurgical anesthesiology.

[13]  R. Singal,et al.  Role of flupirtine in the treatment of pain - chemistry and its effects. , 2012, Maedica.

[14]  Girish M. Bengalorkar,et al.  Flupirtine: Clinical pharmacology , 2012, Journal of anaesthesiology, clinical pharmacology.

[15]  A. Das,et al.  Efficacy and safety of flupirtine maleate and tramadol hydrochloride in postoperative pain management--a prospective randomised double blinded study. , 2012, Journal of the Indian Medical Association.

[16]  B. Terhaag,et al.  Efficacy and tolerability of flupirtine in subacute/ chronic musculoskeletal pain - results of a patient level, pooled re-analysis of randomized, double-blind, controlled trials. , 2011, International journal of clinical pharmacology and therapeutics.

[17]  Michele Tarsilla.  Cochrane Handbook for Systematic Reviews of Interventions , 2010, Journal of MultiDisciplinary Evaluation.

[18]  C. Goodchild,et al.  Combination therapy with flupirtine and opioid: open-label case series in the treatment of neuropathic pain associated with cancer. , 2008, Pain medicine.

[19]  G. Guyatt,et al.  Grading quality of evidence and strength of recommendations , 2004, BMJ : British Medical Journal.

[20]  J. Krieglstein,et al.  Flupirtine protects neurons against excitotoxic or ischemic damage and inhibits the increase in cytosolic Ca2+ concentration. , 1995, European journal of pharmacology.

[21]  M. Ceccarelli,et al.  Analgesic Activity of Flupirtine Maleate: A Controlled Double-Blind Study with Diclofenac Sodium in Orthopaedics , 1988, The Journal of international medical research.

[22]  R. Moore,et al.  Comparison of flupirtine maleate and dihydrocodeine in patients following surgery. , 1983, British journal of anaesthesia.

[23]  Chandrashekhar,et al.  A Comparative Study of the Post Operative Analgesic Efficacy of Flupirtine maleate and Ibuprofen in Patients Undergoing Diagnostic Laparoscopy for Gynaecological Surgeries under General Anaesthesia , 2018 .

[24]  Jai Karan,et al.  A PROSPECTIVE RANDOMIZED COMPARATIVE EVALUATION OF FLUPIRTINE AND DICLOFENAC SODIUM IN POST INGUINAL HERNIA SURGERY PAIN , 2016 .

[25]  Harsimrat Singh,et al.  Comparative evaluation of oral flupirtine and oral diclofenac sodium for analgesia and adverse effects in elective abdominal surgeries , 2015, Anesthesia, essays and researches.

[26]  Roopesh Jain and Bhupendra Kumar Ratre.  FLUPIRTINE REDUCES MORPHINE REQUIREMENTS AFTER CARCINOMA BREAST SURGERY: A RANDOMIZED DOUBLE BLIND CONTROLLED TRIAL. , 2013 .

[27]  J. Higgins.  Cochrane handbook for systematic reviews of interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration , 2011 .

[28]  M. Jane,et al.  Trial of oral flupirtine maleate in the treatment of pain after orthopaedic surgery. , 1985, Current medical research and opinion.