Effect of Etomidate on Pneumonia Development in Critically Ill, Nontrauma Patients

Purpose: To determine whether etomidate use before intubation increased development of hospital-acquired pneumonia (HAP) in critically ill, nontrauma patients. Materials and Methods: A single-center, retrospective, cohort study of critically ill, nontrauma patients admitted to the medical intensive care unit (ICU) from 2012 to 2015 and intubated with or without etomidate was conducted. Demographics, comorbidities, primary diagnosis, critical illness scores, concomitant medications, and outcomes were obtained from medical records. Student t, chi-square, and Fisher exact tests were performed as appropriate. Relevant characteristics were modeled using logistic regression techniques to determine whether any predicted HAP independently. Results: Of the 174 patients, 94 (54%) received etomidate and 80 (46%) did not. There was no difference in HAP between etomidate and no etomidate groups (13.8% vs 23.7%, P = .092). Duration of mechanical ventilation (4.4 vs 4.6 days, P = .845), ICU length of stay (7.4 vs 6.9 days, P = .547), ICU mortality (14.9% vs 12.5%, P = .648), and hospital mortality (17% vs 16.2%, P = .892) were similar between the groups. For each 1-day increase in mechanical ventilation duration, the likelihood of HAP development increased by 21%. Patients who received etomidate but no neuromuscular-blocking drug were 80% less likely to develop HAP than those who did not receive etomidate or a neuromuscular-blocking drug (odds ratio: 0.202, 95% confidence interval: 0.045-0.908). Conclusion: Etomidate use was not associated with a difference in HAP development in critically ill, nontrauma patients.

Dose–response and Cardiopulmonary Side Effects of the Novel Neuromuscular-blocking Drug CW002 in Man

Background CW002 is a benzylisoquinolinium nondepolarizing neuromuscular-blocking drug found to be inactivated by cysteine in preclinical studies. The current study represents a dose escalation clinical trial designed to describe CW002 potency, duration, cardiopulmonary side effects, and histamine release. Methods Healthy subjects anesthetized with sevoflurane/nitrous oxide were divided into five groups (n = 6), each receiving a fixed CW002 dose (0.02, 0.04, 0.06, 0.08, or 0.10 mg/kg), and one group (n = 4) receiving 0.14 mg/kg. Blood pressure and heart rate were continuously recorded along with airway dynamic compliance. Neuromuscular blockade was assessed with mechanomyography at the adductor pollicis. Arterial blood was obtained before and after CW002 injection for analysis of plasma histamine concentration. Potency was estimated from a baseline sigmoid Emax model. Results ED50 was found to be 0.036 mg/kg (95% CI, 0.020 to 0.053 mg/kg) and ED95 0.077 mg/kg (95% CI, 0.044 to 0.114 mg/kg). At 0.14 mg/kg (1.8 × ED95), 80% twitch depression occurred in 94 ± 18 s with complete block in 200 ± 87 s. Clinical recovery (25% of maximum twitch) occurred in 34 ± 3.4 min, with a 5 to 95% recovery interval of 35.0 ± 2.7 min. The time to a train-of-four ratio greater than 0.9 ranged from 59 to 86 min. CW002 did not elicit histamine release or significant (greater than 10%) changes in blood pressure, heart rate, or dynamic airway compliance. Conclusions In healthy subjects receiving sevoflurane/nitrous oxide, CW002 at 1.8 × estimated ED95 produces a clinical duration less than 40 min, elicits no histamine release, and has minimal cardiopulmonary side effects.