Zolpidem reduces pain intensity postoperatively: a systematic review and meta-analysis of the effect of hypnotic medicines on post-operative pain intensity

Abstract

Background: This systematic review aimed to investigate whether the administration of hypnotic medicines, zdrugs, melatonin or benzodiazepines, reduced pain intensity postoperatively. Methods: Medline, Embase, Cinahl, Psych info, Central and PubMed databases were searched, from inception to February 2020 to identify relevant trials. The search was extended, post hoc, to include meta-Register of Controlled Trials, the Web of Science and the conference booklets for the 14th, 15th, and 16th International Association for the Study of Pain conferences. Two independent reviewers screened titles and abstracts and cross-checked the extracted data. Results: The search retrieved 5546 articles. After full-text screening, 15 trials were included, which had randomised 1252 participants. There is moderate-quality evidence that in the short-term [WMD − 1.06, CI − 1.48 to − 0.64, p ≤ .01] and low-quality evidence that in the medium-term [WMD − 0.90, CI − 1.43 to − 0.37, p ≤ .01] postoperative period oral zolpidem 5/10 mg with other analgesic medicines reduced pain intensity compared to the same analgesic medicines alone. There is low-quality evidence that melatonin was not effective on postoperative pain intensity compared to placebo. The results of benzodiazepines on pain intensity were mixed. The authors reported no significant adverse events. Conclusions: There is promising evidence that the hypnotic medicine zolpidem, adjuvant to other analgesics, is effective at achieving a minimally clinically important difference in pain intensity postoperatively. There is no consistent effect of melatonin or benzodiazepines on postoperative pain intensity. Readers should interpret these results with some caution due to the lack of data on safety, the small number of trials included in the pooled effects and their sample sizes. Systematic review registration: The protocol for this systematic review was registered with PROSPERO ID= CRD42015025327.

The relationship between preoperative sleep quality and adverse pain outcomes is still unclear: A Comment on Bjurström et al.

“…We too were interested in understanding how sleep management might be helpful for people with pain and synthesized the evidence available to investigate the effect of hypnotic medicines at reducing pain intensity postoperatively (O'Hagan et al, 2020). The systematic review results show that there was moderate-quality evidence that the hypnotic medicine zolpidem, a z-drug, administered in the postoperative period had an analgesic effect in the short and medium term.…”

Effects of zolpidem administration on postoperative pain in patients after total knee arthroplasty: Study protocol for a randomized controlled trial

“…In addition, patients will be given 400 mg celecoxib 2 h after surgery and an additional 200 mg 6 h after that. Thereafter, 200 mg is administered twice daily until postoperative day 7 [13].…”

“…A medial parapatellar approach will be used to implant a cemented posterior-stabilized prosthesis (Triathlon Systems; Stryker Orthopedics, NJ). Drain will not be used to allow for unrestricted movement [13]. A clinically prescribed postoperative rehabilitation program will be followed.…”

“…Measurements are to be performed for 7 consecutive days after surgery. No contraptions for drainage are to be used after surgery, and sleep quality will be monitored by a mattress-type actigraphy without direct sensors to allow for free movement [13]. We hypothesized that the administration of zolpidem would reduce postoperative pain scores and improve ROM and sleep quality.…”

Managing Perioperative Pain After Anterior Cruciate Ligament (ACL) Reconstruction: Perspectives from a Sports Medicine Surgeon

“…Sedatives described in the management of postoperative pain after ACLR, are typically of the nonbenzodiazepine class including agents such as zolpidem that increase the activity of inhibitory gammaaminobutyric acid (GABA) receptors centrally, and α2-adrenergic agonistic agents such as dexmedetomidine. [76][77][78] Patients receiving 10 mg of zolpidem nightly for the first week postoperatively after ACLR have been shown to have a 28% reduction in opioid consumption. 77 Similarly, a study explored the use of IA dexmedetomidine when used in conjunction with levobupivacaine, versus IA levobupivacaine alone and concluded that those treated with a combination of dexmedetomidine and levobupivacaine had significantly lower opiate consumption, VAS pain scores, and required less analgesics overall in the postoperative period.…”