Intranasal dexmedetomidine vs. nitrous oxide for procedural sedation in juvenile idiopathic arthritis (INDEXJIA): a randomized crossover clinical trial
Jul 2026· European Journal of Pediatrics· Vol 185· 0 citations· 31 references
Medicine
TL;DR
Both intranasal dexmedetomidine and inhaled nitrous oxide offered effective analgosedation for intra-articular injections in children and Nitrous oxide resulted in better patient experience and became their preference for future sedation.
Abstract
This study aims to compare intranasal dexmedetomidine with inhaled nitrous oxide for procedural pain relief and sedation during intra-articular injections in a pediatric rheumatology outpatient clinic. Patients from 1 to 18 years-of-age requiring 1–5 intra-articular injections were randomized to receive 2 µg/kg intranasal dexmedetomidine or inhaled nitrous oxide in the first visit. When the patient required subsequent treatment visit, the other sedative was administered. The primary outcome was patient-reported pain immediately after recovery from sedation. Hemodynamic and respiratory parameters, level of sedation and patient’s pain assessed by the parent, rheumatologist, and nurse were secondary outcomes. Out of 119 eligible patients, 68 were included, and 43 received both medications at two separate visits. Overall pain experience was mild and did not differ between dexmedetomidine and nitrous oxide in patient-reported pain immediately after the procedure (difference, 0.2; 95% CI − 0.7 to 1.2, p = 0.65) but the patients recalled milder pain after nitrous oxide in the follow-up survey (difference, − 1.3; 95% CI − 2.3 to − 0.3; p = 0.01). Milder pain was reported during the second visit compared to the first visit regardless of the sedative used (difference, − 1.2; 95% CI − 2.1 to − 0.2; p = 0.02). In the follow-up survey, majority (69%) of patients would prefer nitrous oxide to dexmedetomidine for sedation in future. Conclusions: Both intranasal dexmedetomidine and inhaled nitrous oxide offered effective analgosedation for intra-articular injections in children. Nitrous oxide resulted in better patient experience and became their preference for future sedation. Trial registration: ClinicalTrials.gov TRN: NCT03069638. https://clinicaltrials.gov/study/NCT03069638. The date of registration 2016–12-20. What is known: • Children suffering juvenile idiopathic arthritis often require repeated intra-articular injections. • Procedural sedation is being used during these procedures. What is New: • When intranasal dexmedetomidine and nitrous oxide was compared in a crossover design both agents provided effective analgosedation without difference in patient-reported pain immediately after the procedure. • Despite this, most patients favored nitrous oxide for future sedation. What is known: • Children suffering juvenile idiopathic arthritis often require repeated intra-articular injections. • Procedural sedation is being used during these procedures. What is New: • When intranasal dexmedetomidine and nitrous oxide was compared in a crossover design both agents provided effective analgosedation without difference in patient-reported pain immediately after the procedure. • Despite this, most patients favored nitrous oxide for future sedation.
The clinical management of established postoperative delirium (POD) is particularly challenging in patients who exhibit agitated behavior and self-remove intravenous (IV) access. A 70-year-old man with prior cerebral infarction developed POD following urologic surgery under general anesthesia. Two doses of IV diazepam failed to provide sustained relief, and the patient subsequently self-removed his IV catheter. Intranasal (IN) dexmedetomidine was administered in a stepwise titration protocol (total dose: 100 μg). The patient transitioned from agitation to calm and entered sustained sleep within 1 h. The only hemodynamic alteration observed was mild bradycardia (heart rate: 58–65 beats/min), with no clinically significant respiratory depression occurring throughout the observation period. The Confusion Assessment Method (CAM) test result was negative on postoperative day 2, and the patient was discharged uneventfully on postoperative day 4. This case suggests that IN dexmedetomidine may offer a safe, non-invasive rescue option for established POD when IV access is unavailable.
Intranasal DEX at a dose of 1.5 mcg/kg is safe and effective premedication for paediatric patients, which results in successful sedation with tolerated changes in vitals, which was well tolerated.
Mona Sharma, Swagat Gongal, B. Yadav et al.· Journal of Nepal Health Rese...· 0 citations
Objectives: The objective of the study was to assess the effectiveness and safety of dexmedetomidine versus midazolam for sedation during regional anesthesia surgery.
Methods: This prospective randomized comparative interventional study was conducted in the Department of Anesthesiology at a tertiary care hospital from January 2025 to January 2026. 100 adult patients undergoing elective surgeries under regional anesthesia were randomly divided into two groups: Group D (dexmedetomidine, n=50) and Group M (midazolam, n=50). Richmond agitation sedation scale (RASS) was used to evaluate sedation. Intraoperative monitoring of hemodynamic parameters, such as mean arterial pressure and heart rate, was performed. Recovery characteristics, patient satisfaction, requirement for rescue sedation and adverse effects were also assessed.
Results: The mean intraoperative RASS score was significantly lower in the Group D than in the Group M (−2.8±0.5 vs. −2.5±0.7; p=0.02). The time required to reach the target sedation level was significantly greater in Group D (9.4±2.6 min vs. 7.8±2.4 min; p=0.003). The scores of patient satisfaction with dexmedetomidine use were significantly greater than with midazolam use (8.5±1.0 vs. 7.9±1.2; p=0.01). Dexmedetomidine was associated with more adverse effects of bradycardia (p=0.08) and hypotension (p=0.46), whereas midazolam was associated with more adverse effects of excessive sedation (p=0.14) and restlessness (p=0.09).
Conclusion: Dexmedetomidine and midazolam were both found to be effective sedatives for patients undergoing regional anesthetic. Dexmedetomidine was found to be a more effective sedative, well tolerated, more patient-satisfying and more stable for intraoperative hemodynamic despite its comparatively slower onset of sedation than midazolam.
AVINASH KAREKAL, SRINIVAS KURAHATTI, Rashmi C· Asian Journal of Pharmaceuti...· 0 citations
Background In this double-blind, randomized controlled trial, we compared the efficacy of perineural 2 µg/kg dexmedetomidine and 5 mg dexamethasone as adjuvants to bupivacaine for postoperative pain control in patients undergoing arthroscopic shoulder surgery. We hypothesized that the combination of bupivacaine with dexmedetomidine would prolong analgesia compared with dexamethasone. Methods One hundred twelve patients scheduled for arthroscopic shoulder surgery were randomized to receive 15 mL of 0.33% bupivacaine with either 2 µg/kg of dexmedetomidine or 5 mg of dexamethasone during ultrasound-guided interscalene brachial plexus block (ISB). The primary outcome was the duration of analgesia (DOA), analyzed as a time-to-event variable using Kaplan–Meier survival curves with log-rank testing. Secondary outcomes included the duration of sensory block (DOS) and motor block (DOM), pain scores, incidence and severity of rebound pain, opioid consumption, patient satisfaction, and adverse effects. Longitudinal pain scores were evaluated using a regression model. Results Of 112 randomized patients, 107 were included in the primary analysis. Dexmedetomidine and dexamethasone produced a similar DOA (median, 16.77 vs 12.48 h; median difference in location 5.24 h, 95% CI −0.47 to 9.17; p = 0.655). The dexmedetomidine group had a significantly longer DOS (19.8 vs. 17.3 h; mean difference 2.45 h, 95% CI 0.23 to 4.65; p = 0.031) and DOM (19.9 vs. 17.8 h; median difference in location 2.23 h, 95% CI 1.02 to 3.60; p = 0.008). Postoperative pain score at 6, 12, 18, and 24 hours were comparable, as were rebound pain, postoperative nausea and vomiting (PONV), patient satisfaction, and opioid consumption. The dexmedetomidine group had a higher incidence of intraoperative hypotension (risk difference [RD] 44.4%, 95% CI 30.0% to 59.9%; p < 0.001), bradycardia in the block room (RD 17.9%; p = 0.010) and intraoperatively (RD 27.6%; p = 0.004), and postoperative sedation (RD 10.9%; p = 0.027); however, all hemodynamic events were transient and did not require intensive care admission. Conclusions Perineural dexmedetomidine (2 µg/kg) was not shown to be superior to dexamethasone (5 mg) in prolonging analgesia when added to bupivacaine for ISB in arthroscopic shoulder surgery. Although dexmedetomidine prolonged sensory and motor block duration, this did not translate into a longer DOA and was associated with higher rates of hemodynamic instability and sedation. These findings suggest limited clinical benefit and raise safety concerns regarding higher dexmedetomidine doses.
Post-dural puncture headache (PDPH) is a common complication after neuraxial anesthesia in obstetrics. While the epidural blood patch (EBP) remains as the gold-standard treatment, less invasive strategies are being increasingly explored. One such intervention is dexmedetomidine (DEX), an alpha-2-adrenergic agonist with analgesic and sedative properties. Method: A comprehensive literature search of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted. Studies evaluating nebulized dexmedetomidine for the treatment of PDPH following neuraxial anesthesia in obstetric patients were included. Comparator groups included saline (placebo), fentanyl, and neostigmine/atropine. The primary outcome was reduction in headache severity measured using the Visual Analog Scale (VAS). Secondary outcomes included adverse events and the need for additional interventions, including epidural blood patch. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Results: Five studies met the inclusion criteria. In most studies, nebulized dexmedetomidine was administered at a dose of 1 μg/kg diluted to a total volume of 4 mL and given every 12 hours for up to 72 hours. Compared with placebo, dexmedetomidine consistently reduced VAS pain scores at 24, 48, and 72 hours and decreased the need for additional treatments. Compared with fentanyl, dexmedetomidine provided superior headache relief, while demonstrating comparable efficacy to neostigmine/atropine. Patients receiving dexmedetomidine were less likely to require rescue therapies or epidural blood patch. Reported adverse events were infrequent and generally mild, including sedation, dry mouth, and bradycardia. Conclusion: Nebulized dexmedetomidine appears to be a safe, effective, and minimally invasive treatment option for PDPH in obstetric patients. It is associated with meaningful reductions in headache severity and may decrease the need for invasive interventions such as epidural blood patch. Larger, high-quality multicenter randomized controlled trials are needed to confirm these findings and define the role of nebulized dexmedetomidine in routine clinical practice.
Sameera Khalid, Hassan Kiani, M. Kiwan et al.· British Journal of Healthcar...· 0 citations
Background Awake percutaneous endoscopic lumbar discectomy (PELD) preserves intraoperative patient feedback, but local infiltration anesthesia may inadequately control pain and anxiety during deeper procedural stages. Intranasal dexmedetomidine offers a noninvasive adjunct, although evidence in this setting remains limited. Methods This two-center retrospective cohort study included 135 adults undergoing PELD with local infiltration anesthesia alone (n=80) or adjunctive intranasal dexmedetomidine (n=55). Pain and anxiety were assessed using the VAS and HADS-A, respectively. VAS scores were analyzed using a linear mixed model adjusted for study center and prespecified covariates. HADS-A scores were analyzed using ANCOVA adjusted for center, baseline HADS-A, and the same patient-level covariates. Results After adjustment for center and prespecified baseline covariates, recorded pain was lower in the intranasal dexmedetomidine group at puncture, channel establishment, annular incision or nucleus removal, and the end of surgery. The largest adjusted difference occurred during annular incision or nucleus removal (mean difference, −1.81; 95% CI, −2.09 to −1.54; Holm-adjusted P<0.001). Rescue analgesia was recorded in 4 of 55 patients (7.3%) versus 18 of 80 (22.5%). Any adverse event was documented in 5 of 55 patients (9.1%) versus 8 of 80 (10.0%). Conclusion In this retrospective cohort, intranasal dexmedetomidine was associated with lower recorded procedural pain and anxiety, lower hemodynamic peaks, and less frequent rescue analgesia. The observational design precludes causal inference and cannot establish safety regarding uncommon events. Prospective randomized evaluation is warranted.
Yonghong Zhou, Chao Pan, Yan Jiang et al.· Journal of Pain Research· 0 citations
