Rheumatology · Medical Literature
Intranasal dexmedetomidine vs. nitrous oxide for procedural sedation in juvenile idiopathic arthritis (INDEXJIA): a randomized crossover clinical trial.
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. 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. • Children suffering juvenile idiopathic arthritis often require repeated intra-articular injections. • Procedural sedation is being used during these procedures. • 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.
Clinical relevance
Children with juvenile idiopathic arthritis (JIA) frequently require repeated intra-articular injections, necessitating safe and effective procedural analgosedation in outpatient rheumatology settings. This randomized crossover trial directly compares two commonly used non-opioid sedation modalities — intranasal dexmedetomidine and inhaled nitrous oxide — in a pediatric population aged 1–18 years, a comparison for which high-quality head-to-head evidence has been lacking. Optimizing sedation choice in this population is clinically urgent given the cumulative procedural burden these patients face over their disease course.
Key findings
1. No statistically significant difference in patient-reported pain immediately after the procedure between intranasal dexmedetomidine (2 µg/kg) and inhaled nitrous oxide (difference: 0.2; 95% CI −0.7 to 1.2; p = 0.65), indicating comparable acute analgosedation efficacy for both agents. 2. At follow-up survey, patients recalled significantly milder pain with nitrous oxide compared to dexmedetomidine (difference: −1.3; 95% CI −2.3 to −0.3; p = 0.01), suggesting a meaningful post-procedural pain memory advantage favoring nitrous oxide. 3. A significant visit-order effect was observed: pain scores during the second visit were milder regardless of which sedative was administered (difference: −1.2; 95% CI −2.1 to −0.2; p = 0.02), indicating procedural habituation or reduced anticipatory anxiety with repeated exposure. 4. Overall procedural pain experience was characterized as mild for both agents across the study cohort, supporting the safety and efficacy of both modalities in a pediatric outpatient rheumatology setting. 5. A majority of patients (69%) expressed preference for nitrous oxide over intranasal dexmedetomidine for future procedural sedation in the follow-up survey. 6. Of 119 eligible patients, 68 were enrolled and 43 completed the crossover design by receiving both agents at two separate visits, providing within-patient comparative data on hemodynamic, respiratory, and sedation-level parameters as secondary outcomes (specific values not reported in the abstract).
Practice implications
Both intranasal dexmedetomidine at 2 µg/kg and inhaled nitrous oxide are viable analgosedation options for outpatient intra-articular injections in children with JIA aged 1–18 years requiring 1–5 joint injections, and either may be selected based on clinical availability and patient factors. However, given the significant patient preference for nitrous oxide (69%) and its superior recalled pain experience at follow-up, nitrous oxide should be considered the preferred first-line agent when feasible, particularly for patients who will require repeated procedures and in whom procedural memory and future cooperation are clinically important. Clinicians should also account for the visit-order analgesic effect (independent of agent used) when counseling families, as pain experiences tend to improve with repeated procedural exposure regardless of sedation modality.