Background Intravenous morphine (IVM) is the most common strong analgesic used in trauma, but is associated with a clear time limitation related to the need to obtain an access route. The intranasal (IN) route provides easy administration with a fast peak action time due to high vascularization and the absence of first-pass metabolism. We aimed to determine whether IN sufentanil (INS) for patients presenting to an emergency department with acute severe traumatic pain results in a reduction in pain intensity non-inferior to IVM. Methods and findings In a prospective, randomized, multicenter non-inferiority trial conducted in the emergency departments of 6 hospitals across France, patients were randomized 1:1 to INS titration (0.3 μg/kg and additional doses of 0.15 μg/kg at 10 minutes and 20 minutes if numerical pain rating scale [NRS] > 3) and intravenous placebo, or to IVM (0.1 mg/kg and additional doses of 0.05 mg/kg at 10 minutes and 20 minutes if NRS > 3) and IN placebo. Patients, clinical staff, and research staff were blinded to the treatment allocation. The primary endpoint was the total decrease on NRS at 30 minutes after first administration. The prespecified non-inferiority margin was −1.3 on the NRS. The primary outcome was analyzed per protocol. Adverse events were prospectively recorded during 4 hours. Among the 194 patients enrolled in the emergency department cohort between November 4, 2013, and April 10, 2016, 157 were randomized, and the protocol was correctly administered in 136 (69 IVM group, 67 INS group, per protocol population, 76% men, median age 40 [IQR 29 to 54] years). The mean difference between NRS at first administration and NRS at 30 minutes was −4.1 (97.5% CI −4.6 to −3.6) in the IVM group and −5.2 (97.5% CI −5.7 to −4.6) in the INS group. Non-inferiority was demonstrated ( p < 0.001 with 1-sided mean-equivalence t test), as the lower 97.5% confidence interval of 0.29 (97.5% CI 0.29 to 1.93) was above the prespecified margin of −1.3. INS was superior to IVM (intention to treat analysis: p = 0.034), but without a clinically significant difference in mean NRS between groups. Six severe adverse events were observed in the INS group and 2 in the IVM group (number needed to harm: 17), including an apparent imbalance for hypoxemia (3 in the INS group versus 1 in the IVM group) and for bradypnea (2 in the INS group versus 0 in the IVM group). The main limitation of the study was that the choice of concomitant analgesics, when they were used, was left to the discretion of the physician in charge, and co-analgesia was more often used in the IVM group. Moreover, the size of the study did not allow us to conclude with certainty about the safety of INS in emergency settings. Conclusions We confirm the non-inferiority of INS compared to IVM for pain reduction at 30 minutes after administration in patients with severe traumatic pain presentin...

Background Intravenous drug infusions in critically ill patients require accurate syringe infusion pumps (SIPs). This is particularly important during transportation of critically ill patients by helicopter emergency medical services (HEMS), where altitude may influence device performance. Because weight is a real concern in HEMS, new low-weight devices are very appealing. The aim of this study was to compare infusion flow rates delivered by low-weight versus standard SIP devices, in the prehospital emergency medicine setting, at different altitudes. Methods We conducted a comparative bench study involving five SIP devices (two standard and three low-weight models) at 300, 1700 and 3000 m altitude. The primary endpoint was the flow rate delivered by SIPs for prespecified values. We used two methods to measure flow. The normative method consisted in measuring weight (method A) and the alternate method consisted in measuring instantaneous flow (method B). Results Using method A, no significant differences were found in median flow rates and interquartile range depending on device and altitude for a prespecified 10-mL/h flow. However, method B showed that low-weight SIPs delivered multiple sequential boluses with substantial variations (1.2–15.8 mL/h) rather than a prespecified continuous 5-mL/h flow. At 1700 m altitude, the interquartile range of delivered flows increased only for low-weight devices ( p for interaction< 0.001). Conclusions Despite satisfactory normative tests, low-weight SIPs deliver discontinuous flow with potential clinical implications for critically ill patients receiving vasoactive drugs. This study also highlights a thus far unknown negative impact of altitude on SIP function. We believe that normative requirements for SIP approval should be revised accordingly.