Perioperative Dexmedetomidine or Lidocaine Infusion for the Prevention of Chronic Postoperative and Neuropathic Pain After Gynecological Surgery: A Randomized, Placebo-Controlled, Double-Blind Study

Martina Rekatsina, Polyxeni Theodosopoulou, Chryssoula Staikou, Martina Rekatsina, Polyxeni Theodosopoulou, Chryssoula Staikou

Abstract

Introduction: The transition of acute to chronic postoperative pain (CPP) remains a significant burden to the rehabilitation of patients. The research for adjuvants to prevent CPP continues; among others, dexmedetomidine and lidocaine seem promising agents.

Methods: This is a long-term follow-up of a randomized, placebo-controlled, double-blind study on women who underwent open abdominal gynecological surgery and received dexmedetomidine or lidocaine or placebo infusion perioperatively (n = 81). The effect of these adjuvants on the development of CPP and neuropathic pain was assessed during a 12-month follow-up. Eighty-one (81) women ASA I-II, aged between 30 and 70 years, were randomly assigned to receive either dexmedetomidine (DEX group) or lidocaine (LIDO group) or placebo (CONTROL group) perioperatively. Before anesthesia induction, all patients received a loading intravenous dose of either 0.6 μg/kg dexmedetomidine or 1.5 mg/kg lidocaine or placebo, followed by 0.6 μg/kg/h dexmedetomidine or 1.5 mg/kg/h lidocaine or placebo until last suture. Patients were followed up to obtain the long-term outcomes at 3, 6, and 12 months. At these time-points, pain intensity was assessed with the Numerical Rating Scale, (NRS: 0-10) and the development of neuropathic elements with the Douleur Neuropathique 4 (DN4) score. Prognostic parameters that could affect chronic pain and its components were also identified.

Results: Data from 74 women were analyzed. Dexmedetomidine significantly reduced NRS scores comparing to placebo at 3 months (p = 0.018), while at 6 months, lidocaine was found superior to placebo (p = 0.02), but not to dexmedetomidine, in preventing neuropathic pain (DN4 < 4). Regarding secondary endpoints, higher NRS cough scores at 48 h were associated with statistically significant NRS and DN4 scores at 3, 6, and 12 months (p < 0.02). At 6 months, a statistically significant correlation was also found between higher NRS values and older age (p = 0.020).

Conclusions: Dexmedetomidine was superior to placebo regarding the duration and severity of CPP, while lidocaine exhibited a protective effect against neuropathic elements of CPP.

Trial registration: ClinicalTrials.gov identifier, NCT03363425.

Keywords: Chronic postoperative pain; Dexmedetomidine; Lidocaine; Long-term follow-up; Neuropathic pain.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
NRS scores compared to 48-h NRS cough scores for all groups at 3, 6, and 12 months
Fig. 2
Fig. 2
DN4 scores at 3, 6, and 12 months for all groups
Fig. 3
Fig. 3
Neuropathic pain at 6 months for all groups

References

    1. Treede RD, et al. A classification of chronic pain for ICD-11. Pain. 2015;156(6):1003–1007. doi: 10.1097/j.pain.0000000000000160.
    1. Gan TJ. Poorly controlled postoperative pain: prevalence, consequences, and prevention. J Pain Res. 2017;10:2287–2298. doi: 10.2147/JPR.S144066.
    1. Parker WH. Uterine myomas: management. Fertil Steril. 2007;88(2):255–271. doi: 10.1016/j.fertnstert.2007.06.044.
    1. Brandsborg B, et al. Chronic pain after hysterectomy. Acta Anaesthesiol Scand. 2008;52(3):327–331. doi: 10.1111/j.1399-6576.2007.01552.x.
    1. Han C, et al. Incidence and risk factors of chronic pain following hysterectomy among Southern Jiangsu Chinese Women. BMC Anesthesiol. 2017;17(1):103. doi: 10.1186/s12871-017-0394-3.
    1. Pinto PR, et al. Risk factors for persistent postsurgical pain in women undergoing hysterectomy due to benign causes: a prospective predictive study. J Pain. 2012;13(11):1045–1057. doi: 10.1016/j.jpain.2012.07.014.
    1. Gimbel H, et al. Randomised controlled trial of total compared with subtotal hysterectomy with one-year follow up results. BJOG. 2003;110(12):1088–1098. doi: 10.1111/j.1471-0528.2003.02395.x.
    1. Humalajärvi N, et al. Quality of life and pelvic floor dysfunction symptoms after hysterectomy with or without pelvic organ prolapse. Eur J Obstet Gynecol Reprod Biol. 2014;182:16–21. doi: 10.1016/j.ejogrb.2014.08.032.
    1. Macrae WA. Chronic post-surgical pain: 10 years on. Br J Anaesth. 2008;101(1):77–86. doi: 10.1093/bja/aen099.
    1. Lavand'homme P. Transition from acute to chronic pain after surgery. Pain. 2017;158(Suppl 1):S50–s54. doi: 10.1097/j.pain.0000000000000809.
    1. Schug SA, Bruce J. Risk stratification for the development of chronic postsurgical pain. Pain Rep. 2017;2(6):e627. doi: 10.1097/PR9.0000000000000627.
    1. Searle R, Simpson K. Chronic post-surgical pain. Contin Educ Anaesth Crit Care Pain. 2009;10(1):12–14. doi: 10.1093/bjaceaccp/mkp041.
    1. Jessen Lundorf L, Korvenius Nedergaard H, Møller AM. Perioperative dexmedetomidine for acute pain after abdominal surgery in adults. Cochrane Database Syst Rev. 2016;2:CD010358.
    1. Galvin IM, et al. Pharmacological interventions for the prevention of acute postoperative pain in adults following brain surgery. Cochrane Database Syst Rev. 2019;2019(11):CD011931.
    1. Jain G, et al. Effect of the perioperative infusion of dexmedetomidine on chronic pain after breast surgery. Indian J Palliat Care. 2012;18(1):45–51. doi: 10.4103/0973-1075.97354.
    1. Liu Y, et al. Dexmedetomidine relieves neuropathic pain in rats with chronic constriction injury via the Keap1-Nrf2 pathway. Front Cell Dev Biol. 2021;9:714996. doi: 10.3389/fcell.2021.714996.
    1. Wang X, Liu Q. Dexmedetomidine relieved neuropathic pain and inflammation response induced by CCI through HMGB1/TLR4/NF-κB signal pathway. Biol Pharm Bull. 2021 doi: 10.1248/bpb.b21-00329.
    1. Dholakia C, et al. The impact of perioperative dexmedetomidine infusion on postoperative narcotic use and duration of stay after laparoscopic bariatric surgery. J Gastrointest Surg. 2007;11(11):1556–1559. doi: 10.1007/s11605-007-0290-0.
    1. Bailey M, et al. Perioperative lidocaine infusions for the prevention of chronic postsurgical pain: a systematic review and meta-analysis of efficacy and safety. Pain. 2018;159(9):1696–1704. doi: 10.1097/j.pain.0000000000001273.
    1. Kendall MC, et al. The effect of intraoperative systemic lidocaine on postoperative persistent pain using initiative on methods, measurement, and pain assessment in clinical trials criteria assessment following breast cancer surgery: a randomized, double-blind placebo-controlled trial. Pain Pract. 2018;18(3):350–359. doi: 10.1111/papr.12611.
    1. Hollmann MW, Durieux ME. Local anesthetics and the inflammatory response: a new therapeutic indication? Anesthesiology. 2000;93(3):858–875. doi: 10.1097/00000542-200009000-00038.
    1. Hollmann MW, et al. Local anesthetic inhibition of G protein-coupled receptor signaling by interference with Galpha(q) protein function. Mol Pharmacol. 2001;59(2):294–301. doi: 10.1124/mol.59.2.294.
    1. Sugimoto M, Uchida I, Mashimo T. Local anaesthetics have different mechanisms and sites of action at the recombinant N-methyl-d-aspartate (NMDA) receptors. Br J Pharmacol. 2003;138(5):876–882. doi: 10.1038/sj.bjp.0705107.
    1. Toner AJ, et al. A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery. Anaesthesia. 2021;76(10):1326–1341. doi: 10.1111/anae.15440.
    1. Herroeder S, et al. Systemic lidocaine shortens length of hospital stay after colorectal surgery: a double-blinded, randomized, placebo-controlled trial. Ann Surg. 2007;246(2):192–200. doi: 10.1097/SLA.0b013e31805dac11.
    1. Koppert W, et al. Perioperative intravenous lidocaine has preventive effects on postoperative pain and morphine consumption after major abdominal surgery. Anesth Analg. 2004;98(4):1050–1055. doi: 10.1213/.
    1. Rekatsina M, Theodosopoulou P, Staikou C. Effects of intravenous dexmedetomidine versus lidocaine on postoperative pain, analgesic consumption and functional recovery after abdominal gynecological surgery: a randomized placebo-controlled double blind study. Pain Physician. 2021;24(7):E997–e1006.
    1. Sykioti P, et al. Validation of the Greek version of the DN4 diagnostic questionnaire for neuropathic pain. Pain Pract. 2015;15(7):627–632. doi: 10.1111/papr.12221.
    1. Zghoul N, et al. Prevalence of chronic pain with neuropathic characteristics: a randomized telephone survey among medical center patients in Kuwait. J Pain Res. 2017;10:679–687. doi: 10.2147/JPR.S123966.
    1. Firth D. Bias reduction of maximum likelihood estimates. Biometrika. 1993;80(1):27–38. doi: 10.1093/biomet/80.1.27.
    1. Wang X. Firth logistic regression for rare variant association tests. Front Genet. 2014;5:187.
    1. Bouhassira D, et al. Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4) Pain. 2005;114(1–2):29–36. doi: 10.1016/j.pain.2004.12.010.
    1. Dai S, et al. Dexmedetomidine attenuates persistent postsurgical pain by upregulating K(+)–Cl(−) cotransporter-2 in the spinal dorsal horn in rats. J Pain Res. 2018;11:993–1004. doi: 10.2147/JPR.S158737.
    1. Harifi G, et al. Validity and reliability of the Arabic adapted version of the DN4 questionnaire (Douleur Neuropathique 4 Questions) for differential diagnosis of pain syndromes with a neuropathic or somatic component. Pain Pract. 2011;11(2):139–147. doi: 10.1111/j.1533-2500.2010.00399.x.
    1. Kandil E, Melikman E, Adinoff B. Lidocaine infusion: a promising therapeutic approach for chronic pain. J Anesth Clin Res. 2017;8(1):697. doi: 10.4172/2155-6148.1000697.
    1. Zhu B, et al. Intra-venous lidocaine to relieve neuropathic pain: a systematic review and meta-analysis. Front Neurol. 2019;10:954–954. doi: 10.3389/fneur.2019.00954.
    1. Fassoulaki A, et al. Acute postoperative pain predicts chronic pain and long-term analgesic requirements after breast surgery for cancer. Acta Anaesthesiol Belg. 2008;59(4):241–248.
    1. Shipton E. Post-surgical neuropathic pain. ANZ J Surg. 2008;78(7):548–555. doi: 10.1111/j.1445-2197.2008.04569.x.
    1. Richebé P, Capdevila X, Rivat C. Persistent postsurgical pain: pathophysiology and preventative pharmacologic considerations. Anesthesiology. 2018;129(3):590–607. doi: 10.1097/ALN.0000000000002238.
    1. Lavand'homme PM, et al. Pain trajectories identify patients at risk of persistent pain after knee arthroplasty: an observational study. Clin Orthop Relat Res. 2014;472(5):1409–1415. doi: 10.1007/s11999-013-3389-5.
    1. Juwara L, et al. Identifying predictive factors for neuropathic pain after breast cancer surgery using machine learning. Int J Med Inform. 2020;141:104170. doi: 10.1016/j.ijmedinf.2020.104170.
    1. Martinez V, et al. Risk factors predictive of chronic postsurgical neuropathic pain: the value of the iliac crest bone harvest model. Pain. 2012;153(7):1478–1483. doi: 10.1016/j.pain.2012.04.004.
    1. Cutler RB, et al. Identifying patients at risk for loss to follow-up after pain center treatment. Pain Med. 2001;2(1):46–51. doi: 10.1046/j.1526-4637.2001.002001046.x.
    1. Beyaz SG, et al. Chronic postsurgical pain and neuropathic symptoms after abdominal hysterectomy: a silent epidemic. Medicine (Baltimore) 2016;95(33):e4484. doi: 10.1097/MD.0000000000004484.

Source: PubMed

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