IMPORTANCE Rocuronium and succinylcholine are often used for rapid sequence intubation, although the comparative efficacy of these paralytic agents for achieving successful intubation in an emergency setting has not been evaluated in clinical trials. Succinylcholine use has been associated with several adverse events not reported with rocuronium.OBJECTIVE To assess the noninferiority of rocuronium vs succinylcholine for tracheal intubation in out-of-hospital emergency situations. DESIGN, SETTING AND PARTICIPANTS Multicenter, single-blind, noninferiority randomized clinical trial comparing rocuronium (1.2 mg/kg) with succinylcholine (1 mg/kg) for rapid sequence intubation in 1248 adult patients needing out-of-hospital tracheal intubation. Enrollment occurred from January 2014 to August 2016 in 17 French out-of-hospital emergency medical units. The date of final follow-up was August 31, 2016.INTERVENTIONS Patients were randomly assigned to undergo tracheal intubation facilitated by rocuronium (n = 624) or succinylcholine (n = 624). MAIN OUTCOMES AND MEASURESThe primary outcome was the intubation success rate on first attempt. A noninferiority margin of 7% was chosen. A per-protocol analysis was prespecified as the primary analysis.RESULTS Among 1248 patients who were randomized (mean age, 56 years; 501 [40.1%] women), 1230 (98.6%) completed the trial and 1226 (98.2%) were included in the per-protocol analysis. The number of patients with successful first-attempt intubation was 455 of 610 (74.6%) in the rocuronium group vs 489 of 616 (79.4%) in the succinylcholine group, with a between-group difference of −4.8% (1-sided 97.5% CI, −9% to ϱ), which did not meet criteria for noninferiority. The most common intubation-related adverse events were hypoxemia (55 of 610 patients [9.0%]) and hypotension (39 of 610 patients [6.4%]) in the rocuronium group and hypoxemia (61 of 616 [9.9%]) and hypotension (62 of 616 patients [10.1%]) in the succinylcholine group.CONCLUSIONS AND RELEVANCE Among patients undergoing endotracheal intubation in an out-of-hospital emergency setting, rocuronium, compared with succinylcholine, failed to demonstrate noninferiority with regard to first-attempt intubation success rate.

ClinicalTrials.gov; No.: NCT01995448; URL: www.clinicaltrials.gov.

ObjectiveAlthough diagnostic guidelines are similar, there is a huge difference in pulmonary embolism (PE) prevalence between the United States of America (US) and countries outside the USA (OUS) in the emergency care setting. In this study, we prospectively analyze patients’ characteristics and differences in clinical care that may influence PE prevalence in different countries.MethodsAn international multicenter prospective diagnostic study was conducted in a standard-of-care setting. Consecutive outpatients presenting to the emergency unit and suspected for PE were managed using the Wells score, STA-Liatest® D-Dimers and imaging.ResultsThe prevalence of PE in the study was 7.9% in low and moderate risk patients. Among the 1060 patients with low or moderate pre-test probability (PTP), PE prevalence was four times higher in OUS (10.7%) than in the US (2.5%) (P < 0.0001). The mean number of imaging procedures performed for one new PE diagnosis was 3.3 in OUS vs 17 in the US (P < 0.001). Stopping investigation in the case of negative D-dimers (DD combined) with low/moderate PTP was more frequent in OUS (92.7%) than in the US (75.7%) (P < 0.01). Moreover, the use of imaging was much higher in the US (44.4% vs 19.2% in OUS) in the case of moderate PTP combined with negative DD.ConclusionDifferences between US and OUS PE prevalence in emergency setting might be explained by differences in patients' characteristics and mostly in care patterns. US physicians performed computed tomographic pulmonary angiography more often than in Europe in cases of low/moderate PTP combined with negative DD.Trial RegistrationClinicalTrials.gov NCT01221805

The main factors of myocardial ischemia are hypoxia, substrate deprivation, acidosis, and high extracellular potassium concentration ([K+]e), but the influence of each of these factors has not yet been evaluated in a cardiomyocyte (CM) culture system. Electromechanical responses to the individual and combined components of ischemia were studied in CM cultured from newborn rat ventricles. Action potentials (APs) were recorded using glass microelectrodes and contractions were monitored photometrically. Glucose-free hypoxia initially reduced AP duration, amplitude, and rate and altered excitation-contraction coupling, but AP upstroke velocity (Vmax) remained unaffected. Early afterdepolarizations appeared, leading to bursts of high-rate triggered impulses before the complete arrest of electromechanical activity after 120 min. Acidosis reduced Vmax whereas AP amplitude and rate were moderately decreased. Combining acidosis and substrate-free hypoxia also decreased Vmax but attenuated the effects of substrate-free hypoxia on APs and delayed the cessation of the electrical activity (180 min). Raising [K+]e reduced the maximal diastolic potential and Vmax. Total ischemia (substrate deletion, hypoxia, acidosis, and high [K+]e) decreased AP amplitude and Vmax without changing AP duration. Moreover, delayed afterdepolarizations appeared, initiating triggered activity. Ultimately, 120 min of total ischemia blocked APs and contractions. To conclude, glucose-free hypoxia caused severe functional defects, acidosis delayed the changes induced by substrate-free hypoxia, and total ischemia induced specific dysfunctions differing from those caused by the former conditions. Heart-cell cultures thus represent a valuable tool to scrutinize the individual and combined components of ischemia on CMs.

Cytoskeleton damage, particularly microtubule (MT) alterations, may play an important role in the pathogenesis of ischemia-induced myocardial injury. However, this disorganization has been scarcely confirmed in the cellular context. We evaluated MT network disassembly in myoblast cell line H9c2 and in neonatal rat cardiomyocytes in an in vitro substrate-free hypoxia model of simulated ischemia (SI). After different duration of SI from 30 up to 180 min, the cells were fixed and the microtubule network was revealed by immunocytochemistry. The microtubule alterations were quantified using a house-developed image analysis program. Additionally, the tubulin fraction were extracted and quantified by Western blotting. The cell respiration, the release of cellular LDH and the cell viability were evaluated at the same periods. An early MT disassembly was observed after 60 min of SI. The decrease in MT fluorescence intensity at 60 and 90 min was correlated with a microtubule disassembly. Conversely, SI-induced significant LDH release (35%) and decrease in cell viability (34%) occurred after 120 min only. These results suggest that the simulated ischemia-induced changes in MT network should not be considered as an ultrastructural hallmark of the cell injury and could rather be an early ultrastructural correlate of the cellular reaction to the metabolic challenge.