This research determined the safety and efficacy of two small-dose infusions of dexmedetomidine by evaluating sedation, analgesia, cognition, and cardiorespiratory function. Seven healthy young volunteers provided informed consent and participated on three occasions with random assignment to drug or placebo. Heart rate, blood pressure, respiratory rate, ETCO(2), O(2) saturation, and processed electroencephalogram (bispectral analysis) were monitored. Baseline hemodynamic measurements were acquired, and psychometric tests were performed (visual analog scale for sedation; observer's assessment of alertness/sedation scale; digit symbol substitution test; and memory). The pain from a 1-min cold pressor test was quantified with a visual analog scale. After a 10-min initial dose of saline or 6 microg. kg(-1). h(-1) dexmedetomidine, volunteers received 50-min IV infusions of saline, or 0.2 or 0.6 microg. kg(-1). h(-1) dexmedetomidine. Measurements were repeated at the end of infusion and during recovery. The two dexmedetomidine infusions resulted in similar and significant sedation (30%-60%), impairment of memory (approximately 50%), and psychomotor performance (28%-41%). Hemodynamics, oxygen saturation, ETCO(2), and respiratory rate were well preserved throughout the infusion and recovery periods. Pain to the cold pressor test was reduced by 30% during dexmedetomidine infusion. Small-dose dexmedetomidine provided sedation, analgesia, and memory and cognitive impairment. These properties might prove useful in a postoperative or intensive care unit setting. IMPLICATIPNS: The alpha(2) agonist, dexmedetomidine, has sedation and analgesic properties. This study quantified these effects, as well as cardiorespiratory, memory and psychomotor effects, in healthy volunteers. Dexmedetomidine infusions resulted in reversible sedation, mild analgesia, and memory impairment without cardiorespiratory compromise.

Arterial baroreflexes contribute importantly to blood pressure regulation through their influence on parasympathetic outflow to the sinus node and sympathetic outflow to the peripheral circulation. Baroreflex control of heart rate is known to be diminished in older individuals. Whether advancing age is associated with a parallel attenuation in baroreflex control of sympathetic outflow to the peripheral circulation has not been studied in humans. To provide such information, we made direct measurements of muscle sympathetic nerve activity (MSNA) in healthy males who ranged in age from 18 to 71 yr. The subjects were arbitrarily divided into three groups: younger (18-34 yr; n = 35), middle aged (35-50 yr; n = 15), and older (51-71 yr; n = 16). Although basal levels of MSNA were higher in older subjects than in younger and middle-aged subjects, the gains of baroreflex control of MSNA were the same in the older, middle-aged, and younger subjects (-4.6 +/- 0.6, -4.8 +/- 0.9, -5.1 +/- 0.5 U/mmHg, P greater than 0.10). In contrast, the gains of baroreflex control of cardiac intervals were attenuated in the older and middle-aged subjects compared with the younger subjects (9.8 +/- 1.2, 13.6 +/- 1.4, 21.7 +/- 1.3 ms/mmHg, P less than 0.05). Our data indicate that although the parasympathetic component of the arterial baroreflex becomes impaired with advancing age, the sympathetic component can be well maintained in healthy individuals even into the seventh decade.

A new, computerized impedance cardiograph (the CIC1000, SORBA Medical Systems, Inc., Milwaukee, WI), which employs ECG R-wave triggered, ensemble-averaging algorithms, was evaluated. The CIC-lo00 and the conventional Kubicek impedance cardiograph were compared and found to provide similar values of stroke volume. In addition, new patch electrodes were tested at various sites and compared to the traditional circumferential band electrodes. The positioning of these electrodes proved to be critical in comparative studies with circumferential band electrodes. The optimal patch electrode array was applied to cardiac patients and compared with thermodilution measurements of cardiac output. The CIC-lo00 cardiac output values were in good agreement (r=0.81) with the thermodilution cardiac output values. Thus the CIC-lo00 may have potential as a clinical monitoring instrument.

The authors have used impedance cardiography as a monitor in many investigations. In one study, cardiac output measurements indicated that cardiopulmonary reflexes were critical in human adjustment to the upright posture. However, a sudden increase in transthoracic Z/sub 0/ during prolonged head-up tilt was found to be an immediate prelude to fainting, suggesting that a rapid shift in blood volume triggered the fainting reaction. In other experiments, the authors developed ensemble-averaging methods which permit online monitoring of blood pressure, cardiac output and thoracic blood volume in postoperative patients. They believe impedance cardiography to be a valuable tool for clinical monitoring of circulatory events.< >

The influence of fitness on cardiac vagal activity and baroreflex-mediated control of heart rate has not been clearly established in humans. Therefore, we studied resting cardiac vagal activity by evaluating respiratory sinus arrhythmia (RSA) and examined carotid-cardiac baroreflex responsiveness with a neck collar in 11 high-fit and 9 sedentary [based on maximal O2 consumption (VO2max) and history of physical activity] healthy young men (19-31 yr of age). Resting cardiac vagal activity was determined from the standard deviation of 100 consecutive resting R-R intervals. Baroreflex responsiveness was determined from the R-R interval responses to neck suction and pressure (repeated trials of 5-s stimuli of -20, -40, and 35 mmHg). Both RSA and the bradycardic (R-R interval) responses to neck suction of -40 mmHg were significantly greater (P less than 0.05) in the high-fit individuals (RSA, 116.5 +/- 11.5 ms; neck-suction response, 145.3 +/- 17.0 ms; mean +/- SE) compared with sedentary subjects (RSA, 65.2 +/- 6.6 ms; neck-suction response, 86.9 +/- 12.5 ms). Responses of the high-fit volunteers to the other intensities of neck stimuli (-20 and 35 mmHg) showed a similar trend but were not significantly different from those of the sedentary volunteers. The baroreflex slope derived from these data was significantly greater in the high-fit subjects (4.00 +/- 0.39 ms/mmHg) compared with the sedentary controls (2.53 +/- 0.28 ms/mmHg). These data suggest that resting cardiac vagal activity is greater, carotid-to-cardiac activity is well maintained, and baroreflex sensitivity, i.e., slope, is augmented in high-fit subjects.

We studied the hemodynamic effect of graded gravity (g) increments from 10 degrees headdown (-0.17 g) to 70 degrees headup (+0.94 g) tilt on young (20 to 29 years), middle-aged (40 to 49 years) and older (60 to 69 years), healthy men. Thoracic blood volume and ventricular stroke volume decreased linearly with increasing g levels. Heart rates and diastolic pressures increased, but only at the higher g levels; however, the increases were significantly less in the 60- to 69-year-old men. The results indicate that thoracic blood volume and ventricular stroke volume are remarkably gravity dependent over the entire tilt range in all groups, the lesser heart rate and diastolic pressure responses in older participants are significant circulatory handicaps and may contribute to the increased incidence of postural hypotension in elderly persons, the sharp rise in vascular resistance at lower +g levels (when arterial pressure is unchanged) suggests that cardiopulmonary reflexes play an important role in human circulatory adjustment to the headup posture.

In these studies, strong inferential evidence is provided which suggests that thoracic impedance provides reliable estimates of thoracic blood volume changes in man. There were 24 volunteers studied in 4 different experiments. The results of these studies are as follows: Impedance derived blood volume changes in the calf of man correlate closely with standard estimates of calf blood volume changes made with strain gauge plethysmography. There is a close linear relationship between the increase of thoracic impedance and the increase of calf blood volume during head-up tilt. Volunteers who develop syncope during head-up tilt (presumably due to excessive decreases of central blood volume) demonstrate exaggerated increases of thoracic impedance. Decreases in central venous pressure produced by lower body negative pressure are significantly correlated to thoracic impedance increases.

Although impedance cardiography provides safe and reliable noninvasive estimates of stroke volume in humans, its usefulness is limited by the necessity for subjects to be apneic and motionless. In an effort to circumvent this restriction we studied the validity of ensemble-averaging of impedance data in exercising normal subjects and in intensive-care patients. The correlation coefficient (r value) between 128 ensemble-averaged and standard hand-digitized determinations of stroke volume index from the same records taken during rest and exercise in six normal male subjects was +0.97 (P less than 0.001). The r value for ensemble-averaged stroke volume indices during free breathing and breath hold in the same subjects was +0.92 (P less than 0.001), suggesting that breath hold did not significantly affect the stroke volume estimation. In 14 freely breathing hospital intensive-care patients the r value between simultaneous thermodilution cardiac output readings and ensemble-averaged impedance determinations was +0.87 (P less than 0.01). The results indicate that ensemble-averaging of transthoracic impedance data provides waveforms from which reliable estimates of cardiac output can be made during normal respiration in healthy human subjects at rest and exercise and in critically ill patients.