Dexmedetomidine is a highly selective α2 adrenergic agonist that has been shown to decrease the intensity of opioid-induced hyperalgesia (OIH). We aimed to investigate the antihyperalgesic effects of dexmedetomidine on high-dose remifentanil-induced hyperalgesia. Ninety American Society of Anesthesiologists physical status I-II patients undergoing laparoscopically assisted vaginal hysterectomy (LAVH) were randomly assigned to one of the following three groups, each of which received either dexmedetomidine (an initial dose of 1.0 µg/kg for 10 min, followed by a continuous infusion of 0.7 µg/kg/hr) or placebo saline 15 min before the induction of anesthesia and intraoperative remifentanil infusion: group C received a placebo and 0.05 µg/kg/min remifentanil; group RH received a placebo and 0.3 µg/kg/min remifentanil; and group DRH received dexmedetomidine and 0.3 µg/kg/min remifentanil. The mechanical hyperalgesia threshold 24 hr after surgery was significantly lower in group RH than in the other two groups. Postoperative pain intensity using visual analog scale (VAS) and cumulative volume of a patient-controlled analgesia (PCA) containing morphine over 24 hr were significantly greater in group RH than in group DRH. The time to the first postoperative analgesic requirement was significantly shorter in group RH than in the other two groups. The desflurane requirement was significantly greater in group C than in the other groups. The frequency of hypotension and bradycardia was significantly higher, but shivering and postoperative nausea and vomiting were significantly lower in group DRH than in the other two groups. High-doses of remifentanil induced hyperalgesia, which presented a decreased mechanical hyperalgesia threshold, enhanced pain intensity, a shorter time to first postoperative analgesic requirement, and greater morphine consumption, but dexmedetomidine efficiently alleviated those symptoms. Dexmedetomidine may be a novel and effective treatment option for preventing or attenuating OIH.

Pregabalin is an antiepileptic drug that is effective for treating postoperative pain, neuropathic pain, anxiety, and hemodynamic instability. The aim of this study was to investigate the effect of a single preoperative dose of pregabalin in patients with opioid-induced hyperalgesia (OIH). Ninety ASA I-II patients undergoing laparoendoscopic single-site urologic surgery were randomly assigned to one of the following three groups that received either pregabalin or placebo 1 h before anesthesia and an intraoperative remifentanil infusion. Group plL received placebo and 0.05 µg/kg/min remifentanil, group plH received placebo and 0.3 µg/kg/min remifentanil, and group prH received 300 mg pregabalin plus 0.3 µg/kg/min remifentanil. The primary endpoint was pain intensity upon movement 1, 6, 12, and 24 h after surgery. Secondary endpoints were the area of hyperalgesia and mechanical hyperalgesia threshold 24 h after surgery, time to first postoperative analgesic requirement, and cumulative postoperative volume of morphine administered via a patient-controlled analgesia (PCA) pump over 24 h. The time to first postoperative analgesic requirement in group plH was significantly shorter than that in group plL. The injected PCA volume was significantly greater in group plH than that in the other two groups. Postoperative pain intensity in group plH was significantly greater than that in the other two groups at 6, 12, and 24 h after surgery. The mechanical hyperalgesia threshold and the area of hyperalgesia around the surgical incision 24 h after surgery in group plH differed significantly from those in the other two groups, which were not significantly different. Adverse effects were comparable among groups. High-dose remifentanil induced hyperalgesia, including increased pain intensity, increased area of hyperalgesia, and decreased mechanical hyperalgesia threshold. These effects were attenuated by oral administration of a single preoperative dose of pregabalin (300 mg) in patients undergoing laparo-endoscopic single-site urologic surgery.

Lee MJ, et al. Korean J Pain. 2015 Jan;28(1):39-44. http://dx.doi.org/10.3344/kjp.2015.28.1.39

High-dose remifentanil-based anesthesia is associated with opioid-induced hyperalgesia (OIH) and postanesthetic shivering (PAS). These effects can be prevented by N-methyl-d-aspartate (NMDA) receptor antagonists. This study aimed to investigate correlations between OIH and PAS caused by high-dose remifentanil and the effects of low-dose ketamine on OIH and PAS. Seventy-five patients scheduled for single-port laparoscopic gynecologic surgery were randomly allocated into three groups, each of which received intraoperative remifentanil: group L at 0.1 µg/kg/min; group H at 0.3 µg/kg/min; and group HK at 0.3 µg/kg/min plus 0.25 mg/kg ketamine just before incision, followed by a continuous infusion of 5 µg/kg/min ketamine until skin closure. PAS, postoperative tactile pain threshold, and the extent of hyperalgesia in group H were significantly different (P < 0.05) than in the other two groups. PAS was significantly correlated with OIH, including mechanically evoked pain such as postoperative tactile pain threshold (r = -0.529, P = 0.01) (r = -0.458, P = 0.021) and the extent of hyperalgesia (r = 0.537, P = 0.002) (r = 0.384, P = 0.031), respectively, in group H and group HK. Notably, both groups were treated with high-dose remifentanil. Tympanic membrane temperature, time to first postoperative analgesic requirement, postoperative pain scores, analgesic consumption, and cumulative patient-controlled analgesia volume containing morphine were comparable in all three groups. OIH, including the enhanced perception of pain, and PAS were both associated with high-dose remifentanil, were significantly correlated and were attenuated by a low dose of ketamine. This suggests that a common mechanism in part mediated through activation of the central glutamatergic system (e.g., NMDA receptors), underlies the two effects caused by high doses of remifentanil.

This systematic review and meta-analysis with trial sequential analysis (TSA) aimed to evaluate the efficacy and safety of remimazolam compared to other sedatives for procedural sedation in older patients. We registered the protocol of this systematic review and meta-analysis with TSA in the PROSPERO network (CRD42023441209). Two investigators performed a systematic, comprehensive, and independent search of the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases to identify randomized controlled trials (RCTs) comparing remimazolam with other sedatives in older patients undergoing procedural sedation. Conventional meta-analysis and TSA were also performed. Seven RCTs (1502 patients) were included. Pooled results demonstrated that remimazolam was associated with a low incidence of hypoxemia, hypotension, bradycardia, respiratory depression, and injection pain. Remimazolam also required a long time to cause loss of consciousness. There were no differences in rates of sedation success, dizziness/headache, postoperative nausea and vomiting, or recovery time. Older patients receiving procedural sedation with remimazolam had a lower risk of hypoxemia, hypotension, bradycardia, respiratory depression, and injection pain than those receiving other sedatives, suggesting that remimazolam may be more suitable for procedural sedation in older patients.

Background: This systematic review and meta-analysis with trial sequential analysis (TSA) aimed to compare perioperative outcomes of peripheral nerve blocks (PNBs) and spinal anesthesia (SA) in elective foot and ankle surgery. Methods: The study protocol was registered in PROSPERO (CRD42021229597). Researchers independently searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant randomized controlled trials (RCTs). Results: Analysis of nine RCTs (n = 802; 399 PNBs, 403 SA) revealed significantly shorter block performance times (WMD: 7.470; 95% CI 6.072 to 8.868), the onset of sensory (WMD: 7.483; 95% CI 2.837 to 12.130) and motor blocks (WMD: 9.071; 95% CI 4.049 to 14.094), durations of sensory (WMD: 458.53; 95% CI 328.296 to 588.765) and motor blocks (WMD: 247.416; 95% CI 95.625 to 399.208), and significantly higher postoperative analgesic requirements (SMD: −1.091; 95% CI −1.634 to −0.549) in the SA group. Additionally, systolic blood pressure (SBP) at 30 min (WMD: 13.950; 95% CI 4.603 to 23.298) was lower in the SA group. Conclusions: The SA demonstrated shorter block performance time, faster onset and shorter duration of sensory and motor blocks, higher postoperative analgesic requirements, and lower SBP at 30 min compared to PNBs in elective foot and ankle surgery.