The Effects of Increasing Plasma Concentrations of Dexmedetomidine in Humans

Since changes of heart period follow changes of cardiac vagal efferent activity quantitatively with nearly fixed latencies, measurements of respiratory sinus arrhythmia may provide insights into human central vagal mechanisms. Accordingly, I measured intervals between heartbeats during controlled breathing (at breathing intervals of 2.5-10 s and nominal tidal volumes of 1,000 and 1,500 ml) in six healthy young men and women. As breathing interval increased, the longest heart periods became longer, the shortest heart periods became shorter, and the peak-valley P-P intervals increased asymptotically. Peak-valley P-P intervals also increased in proportion to tidal volume. However, this influence was small: a 50% increase of tidal volume increased the average peak-valley P-P interval by only about 15%. The phase angles between heart period changes and respiration varied as linear functions of breathing interval. Heart period shortening (cardioacceleration) began in inspiration at short breathing intervals and in expiration at long breathing intervals. Heart period lengthening, however, began in early expiration at all breathing intervals studied. These results point toward a close relationship between variations of respiratory depth and interval and the quantity, periodicity, and timing of vagal cardiac outflow in conscious humans. They suggest that, at usual breathing rates, phasic respiration-related changes of vagal motoneuron activity began in expiration, progress slowly, and are incompletely expressed at fast breathing rates.

Alpha 2-adrenergic agonists decrease sympathetic tone with ensuing attenuation of neuroendocrine and hemodynamic responses to anesthesia and surgery. The effects of dexmedetomidine, a highly specific alpha 2-adrenergic agonist, on these responses have not been reported in patients undergoing coronary artery bypass grafting. Eighty patients scheduled for elective coronary artery bypass grafting received, in a double-blind manner, either a saline placebo or a dexmedetomidine infusion, initially 50 ng.kg-1.min-1 for 30 min before induction of anesthesia with fentanyl, and then 7 ng.kg-1.min-1 unit the end of surgery. Filling pressures, blood pressure, and heart rate were controlled by intravenous fluid and by supplemental anesthetics and vasoactive drugs. Compared with placebo, dexmedetomidine decreased plasma norepinephrine concentrations by 90%, attenuated the increase of blood pressure during anesthesia (3 vs. 24 mmHg) and surgery (2 vs. 14 mmHg), but increased slightly the need for intravenous fluid challenge (29 vs. 20 patients) and induced more hypotension during cardiopulmonary bypass (9 vs. 0 patients). Dexmedetomidine decreased the incidence of intraoperative (2 vs. 13 patients) and postoperative (5 vs. 16 patients) tachycardia. Dexmedetomidine also decreased the need for additional doses of fentanyl (3.1 vs. 5.4), the increments of enflurane (4.4 vs. 5.6), the need for beta blockers (3 vs. 11 patients), and the incidence of fentanyl-induced muscle rigidity (15 vs. 33 patients) and postoperative shivering (13 vs. 23 patients). Intraoperative intravenous infusion of dexmedetomidine to patients undergoing coronary artery revascularization decreased intraoperative sympathetic tone and attenuated hyperdynamic responses to anesthesia and surgery but increased the propensity toward hypotension.