Abstract
Background: Opioid-induced hyperalgesia (OIH) is an adverse
event after exposure to opioids which would increase pain intensity. The
optimal drug to prevent these adverse effects is still unclear. We aimed
to perform a network meta-analysis to compare different pharmacological
interventions in preventing the increase in postoperative pain caused by
OIH.
Methods: Several databases were searched independently for
randomized-controlled trials (RCTs) comparing different pharmacological
interventions in preventing OIH. The primary outcomes were postoperative
pain intensity at rest at 24h and the incidence of postoperative nausea
and vomiting (PONV). Secondary outcomes included pain thresholds at 24h
after surgery, cumulative morphine consumption over 24h, time to first
postoperative analgesic requirement, and the incidence of shivering.
Results: In all, 33 RCTs comprising 1711 patients were
identified. In terms of postoperative pain intensity, amantadine,
magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen
plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S
(+)-ketamine plus methadone were associated with milder pain intensity
than placebo, with amantadine ranked the most effective (SUCRA values
=96.2). In terms of the incidence
of PONV, intervene with dexmedetomidine or flurbiprofen plus
dexmedetomidine means a lower incidence placebo and dexmedetomidine
showed the best result (SUCRA values =90.3).
Conclusions :Amantadine was identified as the best in postoperative pain intensity as
well as non-inferior to placebo in the incidence of PONV.
Dexmedetomidine was the only intervention that is superior to placebo in
all indicators.
Clinical trial registration: CRD42021225361 (PROSPERO).
Keywords: opioid-induced hyperalgesia; pharmacological
interventions; general anesthesia; network meta-analysis; postoperative
pain; postoperative nausea and vomiting