Objectives: Emergence delirium (ED) is a common neurologic complication that can not only distress children and their families in the early postanesthetic period, but can also have adverse effects on children in the long-term. This study aimed to investigate the effects of single-dose dexmedetomidine on ED in children with sevoflurane anesthesia and to observe postoperative behavioral changes through long-term follow-up. Methods: Patients aged 2–7 years, American Society of Anesthesiologists class (ASA) I or II, scheduled for tonsillectomy with and without adenoidectomy were randomized to receive dexmedetomidine 0.5 µg/kg (Group D) or volume-matched normal saline (Group C) over 10 minutes after induction of anesthesia. The primary outcome was the incidence of ED within 30 minutes after extubation. Other outcomes were the incidence of pain, extubation time, post-anesthesia care unit (PACU) length of stay after extubation, adverse events, and the incidence of negative postoperative behavioral changes (NPOBCs). Results: Ninety children completed the study. Compared with the control group (Group C), dexmedetomidine decreased the incidence of ED (31.1% vs 53.3%; P=0.033) and pain (28.9% vs 57.8%; P=0.006), but it prolonged extubation time (P<0.001). PACU length of stay after extubation and the percentage of adverse events were similar between groups. The incidence of NPOBCs in Group D was significantly lower at 1 and 7 days after discharge (33.3% vs 60.0%; P=0.011% and 24.4% vs 46.7%; P=0.028, respectively) than it was in Group C, but no significant difference was found at the 30th day. Conclusion: Dexmedetomidine 0.5 µg/kg reduced the incidence of ED after sevoflurane anesthesia and might be used to prevent NPOBCs. Clinical trials registration: ChiCTR1800016828.

We performed this meta-analysis to evaluate the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) for preventing postoperative nausea and vomiting (PONV) after general anesthesia. We searched PubMed, EMbase, Ovid, Web of Science for relevant randomized controlled trials (RCTs) about TEAS for the prevention of PONV, published through July 31, 2019. The primary outcome was the incidence of PONV, postoperative nausea (PON) and postoperative vomiting (POV) recorded within 24 h after surgery. Secondary outcomes included the numbers of patients needing antiemetic rescue and the incidence of postoperative adverse effects referred to general anesthesia. Data were pooled and analyzed by RevMan 5.3 software. Fourteen RCTs (1653 participants) were included in this meta-analysis. The current results suggested that application of TEAS showed obvious superiority in lower incidence of PONV (relative risk [RR] 0.54, 95% confidence interval [CI] 0.42 to 0.68, P < 0.0001), PON (RR, 0.59, 95% CI 0.49 to 0.71, P < 0.0001), POV (RR 0.46; 95% CI, 0.33 to 0.65, P < 0.0001), lower numbers of patients needing antiemetic rescue (RR 0.56, 95% CI 0.40 to 0.78, P = 0.0005), lower incidence of dizziness (RR 0.43, 95% CI 0.31 to 0.60, P < 0.0001) and pruritus (RR 0.43, 95% CI 0.31 to 0.58, P = 0.02), compared with controlled intervention. TEAS is a reasonable modality to incorporate into a multimodal management approach for the prevention of PONV, PON, POV and associated with lower numbers needing antiemetic rescue, lower incidence of adverse effects after general anesthesia.

The aim of the current meta-analysis was to assess the effect of dexmedetomidine on emergence agitation (EA) and the recovery outcomes after general anesthesia in adults. We searched the PubMed, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and clinicaltrials.gov for relevant randomized controlled trials (RCTs) investigating the effects of dexmedetomidine on the EA in adults after general anesthesia compared with placebo. The primary outcome was the incidence of EA. Secondary outcomes included other recovery outcomes after general anesthesia. Twelve RCTs (842 participants) met the eligibility criteria. A conventional random-effects meta-analysis demonstrated that peri-operative intravenous dexmedetomidine could be effective for the prevention of EA [risk ratio (RR) 0.49, Trial Sequential Analysis (TSA)-adjusted 95% confidence interval (CI) 0.35-0.68, P<0.00001]. In addition, the TSA indicated that the meta-analysis for the incidence of EA reached the required information size (370). Lower number of patients receiving dexmedetomidine required analgesia (P=0.0009). Extubation time was longer (P=0.03) and hypotension (P=0.03) was more common with dexmedetomidine. Moreover, no difference was found in the other outcomes. Dexmedetomidine was shown to effectively decrease the incidence of EA and to reduce postoperative analgesic requirements. Yet, other recovery outcomes including extubation time, length of PACU stay, postoperative residual sedation, hypotension, bradycardia as well as postoperative nausea and vomiting provided no data that could be used to form final conclusions.

Objective: Intrathecal dexmedetomidine (DEX) has been used to prevent shivering in patients undergoing cesarean section. The aim of this meta-analysis was to evaluate whether intrathecal DEX could prevent shivering in cesarean section after spinal anesthesia. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) comparing intrathecal DEX in cesarean section after spinal anesthesia with placebo and reporting on shivering, postoperative nausea and vomiting (PONV), hypotension, and bradycardia. Trial sequential analysis (TSA) was also carried out for RCTs comparing DEX with placebo. This meta-analysis has been registered on PROSPERO, and the registration number is CRD42017071640. Results: Six randomized clinical trials comparing 360 patients were included in this study. Compared with placebo, intrathecal DEX significantly reduced the incidence of shivering (risk ratio [RR]=0.40; 95% CI [0.26, 0.62]; P<0.0001). No significant difference was found in the incidence of PONV (RR=1.34; 95% CI [0.82, 2.18]; P=0.24), hypotension (RR=1.09; 95% CI [0.84, 1.42]; P=0.50), or bradycardia (RR=1.55; 95% CI [0.54, 4.42]; P=0.42). However, no firm conclusions can be made based on the results of all outcomes according to the TSA. Conclusion: This meta-analysis found that intrathecal DEX could prevent shivering in cesarean section after spinal anesthesia and did not induce PONV, hypotension, or bradycardia. However, firm conclusions cannot be made until more studies are conducted.

Purpose: Preventing opioid-induced hyperalgesia and tolerance continues to be a major clinical challenge, and the underlying mechanisms of hyperalgesia and tolerance remain elusive. Here, we investigated the role of sonic hedgehog (Shh) signaling in opioid-induced hyperalgesia and tolerance. Methods: Shh signaling expression, behavioral changes, and neurochemical alterations induced by morphine were analyzed in male adult CD-1 mice with repeated administration of morphine. To investigate the contribution of Shh to morphine-induced hyperalgesia (MIH) and tolerance, Shh signaling inhibitor cyclopamine and Shh small interfering RNA (siRNA) were used. To explore the mechanisms of Shh signaling in MIH and tolerance, brain-derived neurotrophic factor (BDNF) inhibitor K252 and anti-BDNF antibody were used. Results: Repeated administration of morphine produced obvious hyperalgesia and tolerance. The behavioral changes were correlated with the upregulation and activation of morphine treatment-induced Shh signaling. Pharmacologic and genetic inhibition of Shh signaling significantly delayed the generation of MIH and tolerance and associated neurochemical changes. Chronic morphine administration also induced upregulation of BDNF. Inhibiting BDNF effectively delayed the generation of MIH and tolerance. The upregulation of BDNF induced by morphine was significantly suppressed by inhibiting Shh signaling. In naïve mice, exogenous activation of Shh signaling caused a rapid increase of BDNF expression, as well as thermal hyperalgesia. Inhibiting BDNF significantly suppressed smoothened agonist-induced hyperalgesia. Conclusion: These findings suggest that Shh signaling may be a critical mediator for MIH and tolerance by regulating BDNF expression. Inhibiting Shh signaling, especially during the early phase, may effectively delay or suppress MIH and tolerance.

Treating bone cancer pain continues to be a clinical challenge and underlying mechanisms of bone cancer pain remain elusive. Here, we reported that sonic hedgehog signaling plays a critical role in the development of bone cancer pain. Tibia bone cavity tumor cell implantation produces bone cancer-related mechanical allodynia, thermal hyperalgesia, and spontaneous and movement-evoked pain behaviors. Production and persistence of these pain behaviors are well correlated with tumor cell implantation-induced up-regulation and activation of sonic hedgehog signaling in primary sensory neurons and spinal cord. Spinal administration of sonic hedgehog signaling inhibitor cyclopamine prevents and reverses the induction and persistence of bone cancer pain without affecting normal pain sensitivity. Inhibiting sonic hedgehog signaling activation with cyclopamine, in vivo or in vitro, greatly suppresses tumor cell implantation-induced increase of intracellular Ca ²⁺ and hyperexcitability of the sensory neurons and also the activation of GluN2B receptor and the subsequent Ca ²⁺ -dependent signals CaMKII and CREB in dorsal root ganglion and the spinal cord. These findings show a critical mechanism underlying the pathogenesis of bone cancer pain and suggest that targeting sonic hedgehog signaling may be an effective approach for treating bone cancer pain.