Safety and efficacy of intravenous combination sedatives in the ED.

OBJECTIVE: The objective of the study is to determine the safety of intravenously administered combination sedatives in the emergency department (ED). METHODS: This was a retrospective study of alcohol-intoxicated patients in the ED. We examined the incidence of adverse events in agitated patients who received combination sedatives intravenously and compared the efficacy of combination sedatives and single-agent sedatives. RESULTS: Of 1300 patient visits, there was a single adverse event, a dystonic reaction, in the combination sedative group, for an adverse event rate of less than 1%. Patients who received combination sedatives were less likely to require a second dose of sedative medication than patients who received a single-agent sedative (21% vs 44%). CONCLUSIONS: Combination sedatives appear to be safe when administered intravenously in the ED. Combination sedatives may be more effective than single-agent sedatives in agitated alcohol-intoxicated patients.

Mechanisms of inhaled fine particulate air pollution-induced arterial blood pressure changes.

BACKGROUND: Epidemiologic studies suggest a positive association between fine particulate matter and arterial blood pressure, but the results have been inconsistent. OBJECTIVES: We investigated the effect of ambient particles on systemic hemodynamics during a 5-hr exposure to concentrated ambient air particles (CAPs) or filtered air (FA) in conscious canines. METHODS: Thirteen dogs were repeatedly exposed via permanent tracheostomy to CAPs (358.1+/-306.7 microg/m3, mean+/-SD) or FA in a crossover protocol (55 CAPs days, 63 FA days). Femoral artery blood pressure was monitored continuously via implanted telemetry devices. We measured baroreceptor reflex sensitivity before and after exposure in a subset of these experiments (n=10 dogs, 19 CAPs days, 20 FA days). In additional experiments, we administered alpha-adrenergic blockade before exposure (n=8 dogs, 16 CAPs days, 15 FA days). Blood pressure, heart rate, rate-pressure product, and baroreceptor reflex sensitivity responses were compared using linear mixed-effects models. RESULTS: CAPs exposure increased systolic blood pressure (2.7+/-1.0 mmHg, p=0.006), diastolic blood pressure (4.1+/-0.8 mmHg; p<0.001), mean arterial pressure (3.7+/-0.8 mmHg; p<0.001), heart rate (1.6+/-0.5 bpm; p<0.001), and rate-pressure product (539+/-110 bpm x mmHg; p<0.001), and decreased pulse pressure (-1.7+/-0.7 mmHg, p=0.02). These changes were accompanied by a 20+/-6 msec/mmHg (p=0.005) increase in baroreceptor reflex sensitivity after CAPs versus FA. After alpha-adrenergic blockade, responses to CAPs and FA no longer differed significantly. CONCLUSIONS: Controlled exposure to ambient particles elevates arterial blood pressure. Increased peripheral vascular resistance may mediate these changes, whereas increased baroreceptor reflex sensitivity may compensate for particle-induced alterations in blood pressure.

Suppression of calcium-induced repolarization heterogeneity as a mechanism of nitroglycerin's antiarrhythmic action.

This study examined whether the antifibrillatory action of nitroglycerin (NTG) is attributable to reduction in calcium-induced heterogeneity of repolarization independent of autonomic and coronary vasodilatory influences. The effects of intrapericardial (IPC) NTG on coronary blood flow, contractility, repolarization, and arrhythmia susceptibility were measured in anesthetized pigs (N = 43). Autonomic influences were minimized by vagotomy and beta-adrenergic blockade (metoprolol, 1.25 mg/kg, intravenous). Electrophysiological parameters were tested at 30 min, a time when coronary hemodynamics had returned to baseline. Intracoronary calcium chloride (CaCl2, 50-mg bolus) injection augmented contractility (dP/dt(max), 1760 +/- 144 to 2769 +/- 274 mmHg/s, and following NTG, 1531 +/- 384 to 2138 +/- 242 mmHg/s, P < 0.0002), reflecting increased myocardial intracellular calcium. Calcium increased repolarization heterogeneity (interlead precordial T-wave heterogeneity, 95 +/- 15 to 264 +/- 33 microV, P < 0.006; T(peak)-T(end), an index of transmural dispersion of repolarization, 37 +/- 3 to 76 +/- 6 ms, P < 0.05) and lowered repetitive extrasystole threshold (RET; 24 +/- 2 to 13 +/- 1 mA, and following NTG, 32 +/- 4 to 18 +/- 1 mA, P < 0.0001). IPC NTG raised the RET from baseline by 33% and blunted calcium-induced contractility (dP/dt(max) by 23%, P < 0.05), repolarization changes (T-wave heterogeneity by 24%, P < 0.006; T(peak)-T(end) by 18%, P = 0.04), and arrhythmia vulnerability (RET by 39%, P < 0.003). Thus, the capacity of NTG to suppress calcium-induced repolarization heterogeneity is an important mechanism of its antiarrhythmic action, which is independent of autonomic and vasodilatory actions.