Etomidate versus ketamine for emergency endotracheal intubation: a randomized clinical trial.

PURPOSE: Etomidate and ketamine are hemodynamically stable induction agents often used to sedate critically ill patients during emergency endotracheal intubation. In 2015, quality improvement data from our hospital suggested a survival benefit at Day 7 from avoidance of etomidate in critically ill patients during emergency intubation. In this clinical trial, we hypothesized that randomization to ketamine instead of etomidate would be associated with Day 7 survival after emergency endotracheal intubation. METHODS: A prospective, randomized, open-label, parallel assignment, single-center clinical trial performed by an anesthesiology-based Airway Team under emergent circumstances at one high-volume medical center in the United States. 801 critically ill patients requiring emergency intubation were randomly assigned 1:1 by computer-generated, pre-randomized sealed envelopes to receive etomidate (0.2-0.3 mg/kg, n = 400) or ketamine (1-2 mg/kg, n = 401) for sedation prior to intubation. The pre-specified primary endpoint of the trial was Day 7 survival. Secondary endpoints included Day 28 survival. RESULTS: Of the 801 enrolled patients, 396 were analyzed in the etomidate arm, and 395 in the ketamine arm. Day 7 survival was significantly lower in the etomidate arm than in the ketamine arm (77.3% versus 85.1%, difference - 7.8, 95% confidence interval - 13, - 2.4, p = 0.005). Day 28 survival rates for the two groups were not significantly different (etomidate 64.1%, ketamine 66.8%, difference - 2.7, 95% confidence interval - 9.3, 3.9, p = 0.294). CONCLUSION: While the primary outcome of Day 7 survival was greater in patients randomized to ketamine, there was no significant difference in survival by Day 28.

A specific force deficit exists in skeletal muscle after partial denervation.

Skeletal muscle demonstrates a specific force deficit after repair of injured peripheral nerves, microneurovascular muscle transfer, and normal aging. Because atrophy cannot account for deficits in specific force, other, unknown, mechanisms are responsible for the resulting muscle contractile dysfunction under these circumstances. We tested the hypothesis that a subpopulation of denervated fibers is partially or completely responsible for the specific force deficit after partial denervation of the rat extensor digitorum longus muscle (EDL). Adult Fisher rats underwent either sham exposure or partial transection of 80% of the cross-sectional area of the left deep peroneal nerve. After a 2-week recovery period, maximum isometric force (F(0)) was measured in situ and maximum specific force (sF(0)) was calculated for EDL from both control (n = 8) and partial denervation (n = 7) groups. Innervated fiber cross-sectional area (CSA(inn)) was measured directly from whole EDL cross sections after immunohistochemical labeling for neural cell adhesion molecule (NCAM), a marker of muscle fiber denervation. A corrected specific force value (sF(0-inn)) was calculated by normalizing F(0) to CSA(inn). Partial skeletal muscle denervation resulted in significant reductions in muscle mass, F(0), and sF(0). The percentage of muscle fibers expressing NCAM in the extrajunctional sarcolemma increased from 1.0 +/- 0.8% in control to 49 +/- 15% in partially denervated EDL muscles. A 62.7% deficit in EDL specific force was observed after partial denervation. Denervated muscle fibers accounted for 59.3% of this deficit, but sF(0-inn) still differed significantly between control and partially denervated muscles, with a 25.5% difference between groups. In partially denervated muscles, the specific force deficit is partially but not fully explained by a subpopulation of noncontractile, denervated fibers.