High concentrations of isoflurane do not block the sympathetic nervous system activation from desflurane.

PURPOSE: The volatile anesthetic desflurane has been associated with neurocirculatory responses that have been relatively refractory to adjuvant treatment. We have employed desflurane to evaluate the integrity of the sympathetic nerve recording after establishment of the anesthetized state with another anesthetic agent. This retrospective evaluation of data from volunteers determined if higher concentrations of isoflurane that were sufficient to block the neurocirculatory response to laryngeal and tracheal stimulation would abolish the neurocirculatory response to desflurane. METHODS: Data from eight, healthy, young volunteers met our criteria for inclusion. They had been anesthetized with propofol or thiopental and intubated after neuromuscular blockade. Each subject was monitored with radial artery blood pressure (BP), heart rate (HR)(ECG), and sympathetic microneurography. Isoflurane had been administered to achieve a steady state concentration of 1.5 MAC (minimum alveolar concentration) while oxygenation and carbon dioxide were monitored with pulse oximetry and infrared spectrometry, respectively. A deep level of anesthesia was confirmed when laryngoscopy and endotracheal tube movement failed to elicit a neurocirculatory response. A brief exposure to 11% desflurane in the inspired gas was then provided. RESULTS: The responses to desflurane included significant increases in HR, range 32-84 b/min, and BP, range 15-72 mm Hg (P < 0.05). Sympathetic nerve activity increased substantially in the three volunteers with functional nerve recordings. CONCLUSION: In healthy volunteers receiving 1.5 MAC isoflurane, which was sufficient to block the neurocirculatory response to laryngoscopy and tracheal stimulation, there were striking increases in sympathetic outflow, HR and BP when 11% desflurane was substituted for isoflurane.

The effects of increasing plasma concentrations of dexmedetomidine in humans.

BACKGROUND: This study determined the responses to increasing plasma concentrations of dexmedetomidine in humans. METHODS: Ten healthy men (20-27 yr) provided informed consent and were monitored (underwent electrocardiography, measured arterial, central venous [CVP] and pulmonary artery [PAP] pressures, cardiac output, oxygen saturation, end-tidal carbon dioxide [ETCO2], respiration, blood gas, and catecholamines). Hemodynamic measurements, blood sampling, and psychometric, cold pressor, and baroreflex tests were performed at rest and during sequential 40-min intravenous target infusions of dexmedetomidine (0.5, 0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml; baroreflex testing only at 0.5 and 0.8 ng/ml). RESULTS: The initial dose of dexmedetomidine decreased catecholamines 45-76% and eliminated the norepinephrine increase that was seen during the cold pressor test. Catecholamine suppression persisted in subsequent infusions. The first two doses of dexmedetomidine increased sedation 38 and 65%, and lowered mean arterial pressure by 13%, but did not change central venous pressure or pulmonary artery pressure. Subsequent higher doses increased sedation, all pressures, and calculated vascular resistance, and resulted in significant decreases in heart rate, cardiac output, and stroke volume. Recall and recognition decreased at a dose of more than 0.7 ng/ml. The pain rating and mean arterial pressure increase to cold pressor test progressively diminished as the dexmedetomidine dose increased. The baroreflex heart rate slowing as a result of phenylephrine challenge was potentiated at both doses of dexmedetomidine. Respiratory variables were minimally changed during infusions, whereas acid-base was unchanged. CONCLUSIONS: Increasing concentrations of dexmedetomidine in humans resulted in progressive increases in sedation and analgesia, decreases in heart rate, cardiac output, and memory. A biphasic (low, then high) dose-response relation for mean arterial pressure, pulmonary arterial pressure, and vascular resistances, and an attenuation of the cold pressor response also were observed.

Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions.

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.

Effects of aging on baroreflex regulation of sympathetic activity in humans.

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.

Endometrioid carcinoma arising in endometriosis after 21 years: a case report.

Endometriosis is an odd disease that is at times devastating in the destruction of surrounding tissue. Yet, in contradiction, other cases are widespread, longstanding, benign, and totally asymptomatic. It has been reported throughout the body.

Impedance-derived cardiac indices in supine and upright exercise.

Impedance cardiography was used to determine the classical systolic time intervals (STI's) (i.e., pre-ejection period (PEP), left ventricular ejection time (LVET) and the quotient PEP/LVET), in young, healthy, male subjects during supine and seated exercise. With increasing exercise, there was a tendency toward decreases in PEP, LVET, and PEP/LVET. In the seated position, there was an increase in transthoracic Zo incident to the caudal migration of thoracic blood--a result of the postural change. With seated exercise, there were--in contrast to supine exercise-greater decreases in PEP/LVET and greater increases in the Heather index. Similarly, there was a tendency toward increases in dZ/dtmin and the Rapid Ejection Index. We suggest that these differences are related to increased myocardial contractility resulting from the postural augmentation of cardio-sympathetic activity, added to that of exercise per se. This study, as well as previous ones, indicates that impedance cardiography is reliable, effective, and more practicable than the arteriographic method for monitoring STI's. We also believe that certain impedance-derived indices (i.e., transthoracic Zo, dZ/dtmin and the Heather Index) have considerable potential value for physiologic and clinical investigation.

Carotid baroreflex responsiveness in high-fit and sedentary young men.

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.

The effect of age on hemodynamic response to graded postural stress in normal men.

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.

The use of thoracic impedance for determining thoracic blood volume changes in man.

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.

Determination of cardiac output using ensemble-averaged impedance cardiograms.

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.

Baroreceptor reflex control of heart rate during isoflurane anesthesia in humans.

The effect of isoflurane alone (Group 1) and isoflurane following thiopental (Groups 2 and 3) on baroreflex control of heart rate in humans was investigated in this study. Phenylephrine (the pressor test) and sodium nitroprusside (the depressor test) were used to induce moderate changes in arterial blood pressure and to alter the stimulation of baroreceptor sites. In addition, graded neck suction was employed to examine carotid baroreflex control of heart rate. In Group 3 subjects, phenylephrine was infused continuously during anesthesia to maintain mean arterial blood pressure near control levels. The pressor- and neck-suction-derived baroreflex slopes were decreased progressively from awake to 1.0 and 1.5 MAC isoflurane. The slopes of the depressor responses were decreased at 1.0 MAC but showed little further depression at 1.5 MAC. For each method, the depression of baroreceptor slopes from control to 1.0 MAC and 1.5 MAC was similar among the three groups. Maintenance of arterial blood pressure (Group 3) and the utilization of thiopental (Group 2) did not significantly alter the depression of baroreflex responses during increasing levels of isoflurane anesthesia. Neck suction derived slopes compared favorably with the pressor test slopes (r = 0.75, P less than 0.001). This study indicates that the depression of arterial baroreflex heart rate responses under isoflurane anesthesia are less pronounced than the depression of baroreflex responses noted by other investigators for halothane or enflurane. The neck suction technique appears to be a sensitive method useful in assessing the carotid sinus reflex in awake and anesthetized humans.

Summated circulatory responses of thermal and baroreflexes in humans.

Baroreceptor and thermal receptor mediated reflexes are important neural control systems that can markedly alter blood pressure in humans. These two systems have different afferent limbs and are integrated at different central sites. Although the circulatory effects of activating these individual reflexes have been examined, the effects of simultaneous activation of two or more separate reflexes have received relatively little attention. We used noninvasive methods in 13 normal men (20-27 yr) to examine the responses mediated by cardiopulmonary and arterial baroreceptors; the reflexes were elicited by alterations in central blood volume [lower body negative pressure (LBNP) and leg elevation (LE)] in the presence or absence of local thermal receptor stimulation induced by hand immersion (HI) in 10 degree C water. During all levels (-10, -25, and -40 Torr) of LBNP and during LE, forearm vascular resistance (FVR) was altered. At the two higher levels of LBNP, stroke volume, cardiac index, and blood pressure (BP) decreased, and heart rate (HR) and total peripheral resistance (TPR) increased. TPR, FVR, and BP increased during HI. Our analyses indicated that responses to combined stimuli, i.e., local cold during LBNP or LE, resulted in simple additive responses in all variables except HR. A central interaction between thermal and baroreflex control of HR is possible.