Denham S. Ward

Effects of intravenous dexmedetomidine in humans. II: Hemodynamic changes

Dexmedetomidine (DMED) is a novel clonidine-like compound known to have sedative, analgesic, and cardiovascular stabilizing qualities. DMED is a more highly selective alpha 2-adrenergic agonist than clonidine. This investigation examined the hemodynamic effects of four selected iv doses in consenting healthy male volunteers. In a randomized, double-blind, placebo-controlled trial subjects received 0 (n = 9), 0.25 (n = 6) 0.5 (n = 6), 1.0 (n = 6), or 2.0 (n = 10) micrograms/kg of DMED by infusion (2 min). ECG, heart rate (HR), arterial blood pressure (MABP), bioimpedance cardiac output (CO), and plasma catecholamines concentrations (CA) were monitored from 90 min before to 360 min after infusion. Plasma DMED concentrations were measured. DMED produced a maximum decrease in MABP at 60 min of 14%, 16%, 23%, and 27% for the 0.25, 0.5, 1.0, and 2.0 micrograms/kg groups, respectively (P < .05). At 330 min MABP remained below baseline by 8% and 17% at the two largest doses (P < .05). Both HR and CO decreased maximally by both 17% at 105 min. The two largest doses produced a transient (peak at 3 min lasting < 11 min) increased in MABP (16 +/- 2.5 and 24 +/- 10 mmHg, respectively; P < .05) with a concomitantly reduced CO (41%, 2 micrograms/kg; P < .05) and HR (22%, 2 micrograms/kg; P < .05), whereas systemic vascular resistance doubled. Even the lowest dose decreased CA immediately to values close to 20 pg/ml for 5 h. A 2-min iv infusion of DMED produced a transient increase in MABP and a longer lasting decrease in MABP and CA. These DMED doses were well tolerated in the healthy volunteers.

Effects of intravenous dexmedetomidine in humans. I. Sedation, ventilation, and metabolic rate.

Dexmedetomidine (DMED) is a highly selective centrally acting alpha 2-adrenergic agonist thought to provide significant sedation without appreciable ventilatory effects. This double-blind, placebo-controlled experiment evaluated four dose levels of DMED (0.25, 0.5, 1.0, and 2.0 micrograms/kg intravenously over 2 min) in 37 healthy male volunteers. Measurements of sedation, arterial blood gases, resting ventilation, hypercapnic ventilatory response (HVR), and metabolic rate (O2 consumption and CO2 production) were performed at baseline, 10 min after DMED infusion, and thereafter at the end of each subsequent 45-min period. DMED caused sedation resulting in loss of responsiveness in most of the subjects administered 1.0 and 2.0 micrograms/kg; sedation was evident for 195 min following 2.0 micrograms/kg (P < .05). Ten minutes following infusion of 1.0 and 2.0 micrograms/kg, PaCO2 had increased by 5.0 and 4.2 mmHg, respectively (P < .05), and 60 min following 2.0 micrograms/kg, VE had decreased by 28% (P < .05). The placebo group showed a progressive increase in the HVR slope (50% increase by 330 min following the infusion; P < .05). Overall, across all the DMED doses, the slope was decreased (P < .05) at all times after DMED. The calculated ventilation at a PaCO2 of 55 mmHg was decreased (39%; P < .05) 10 min following 1.0 and 2.0 micrograms/kg, returning to control values by 285 min following 2.0 micrograms/kg. O2 consumption increased 16% (P < .05) at 10 min following 2.0 micrograms/kg; CO2 production decreased (22% at 60 min). By 5 h postinfusion, both had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of jugular venous O2 saturation from cerebral oximetry or arterial O2 saturation during isocapnic hypoxia.

AbstractObjective.Near-infrared spectroscopy (NIRS) has the potential forproviding valuable information about oxygen delivery to the brain. However,questions have been raised about the accuracy of these measurements. Thisstudy was undertaken to compare noninvasive cerebral saturation measurementsto jugular venous saturation under conditions of hypoxia and hypercapnia.Methods.Data was obtain on forty-two subjects. Cerebral oxygenationwas measured with a Somanetics INVOS 4100-SSA placed on the forehead of thesubjects. PETCO2 was controlled to approximately 2 and 7 mmHg aboveresting values and PETO2 was controlled to 80, 45, 60 and 41 mmHgconsecutively for four of five minutes each. Internal jugular blood gasmeasurements were made via a retrograde catheter. Results.Both thecerebral oximetry measured saturation (rSO2) and the jugular venoussaturation (Sj

Response surface modeling of remifentanil-propofol interaction on cardiorespiratory control and bispectral index.

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Chloral Hydrate Sedation: The Additive Sedative and Respiratory Depressant Effects of Nitrous Oxide

O2) were significantly increasedby increasing the PETCO2 at all levels of hypoxia. The increase inthe rSO2 was less than the increase inSj

Breathing patterns and levels of consciousness in children during administration of nitrous oxide after oral midazolam premedication

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