The thermoregulatory threshold in humans during nitrous oxide-fentanyl anesthesia

Narcotics and nitrous oxide (N2O) inhibit thermoregulatory responses in animals. The extent to which N2O/fentanyl anesthesia lowers the thermoregulatory threshold in humans was tested by measuring peripheral cutaneous vasoconstriction using skin-surface temperature gradients (forearm temperature-fingertip temperature) and the laser Doppler perfusion index. Fifteen unpremedicated patients were anesthetized with N2O (70%) and fentanyl (10 micrograms/kg iv bolus followed by 4 micrograms.kg-1.h-1 infusion) during elective, donor nephrectomy. Patients were randomly assigned to undergo additional warming (humidified respiratory gases, warmed intravenous fluids, and a heating blanket over the legs; n = 5) or standard temperature management (no special warming measures; n = 10). Significant vasoconstriction was prospectively defined as a skin-surface temperature gradient between forearm surface and finger-tip surface greater than or equal to 4 degrees C, and the thermoregulatory threshold was defined as the esophageal temperature at which such vasoconstriction occurred. Vasoconstriction did not occur in the patients who received additional warming and thus remained nearly normothermic [average minimum esophageal temperature = 35.8 +/- 0.4 degrees C (SD)] but did in six hypothermic patients at a mean esophageal temperature of 34.2 +/- 0.5 degrees C. Four hypothermic patients developed a passive thermal steady state without becoming sufficiently cold to trigger vasoconstriction. Thus, active thermoregulation occurs during N2O/fentanyl anesthesia but does not occur until core temperatures are approximately 2.5 degrees C lower than normal. The thermoregulatory threshold during N2O/fentanyl anesthesia is similar to that previously determined during halothane (34.4 +/- 0.2 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)     

Atracurium during halothane anesthesia in humans

The neuromuscular effects of atracurium were studied in 20 patients anesthetized with 0.8% end-tidal halothane. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from stimulation of the ulnar nerve. Four groups of five patients received single atracurium doses of 0.1, 0.15, 0.2, or 0.4 mg/kg, respectively. The block produced by 0.1 mg/kg was 25-72% and lasted 6-21 min. The block produced by 0.15 mg/kg was 69-93% and lasted 16-32 min. The blocks produced by 0.2 and 0.4 mg/kg were 95% or greater and lasted 42-84 min and 55-104 min, respectively. When indicated, intubation was easily performed in all patients receiving 0.2 and 0.4 mg/kg. The block could be readily antagonized by neostigmine and atropine. Changes in heart rate and blood pressure following atracurium administration averaged less than 5%.     

Painful stimulation minimally increases the thermoregulatory threshold for vasoconstriction during enflurane anesthesia in humans.

Generalized autonomic stimulation enhances hemodynamic responses and may, in a similar fashion, facilitate thermoregulatory responses. We thus tested the hypothesis that painful stimulation increases the central temperature threshold for vasoconstriction during general anesthesia. Healthy volunteers were anesthetized with 1.3% end-tidal enflurane on 2 separate days. On 1 day (randomly assigned), painful stimulation was produced by tetanic electrical stimulation. On the other day, electrical stimulation was not given. Significant thermoregulatory vasoconstriction was defined as a forearm-fingertip skin-surface temperature gradient exceeding 4 degrees C. The distal esophageal temperature triggering significant vasoconstriction was considered the thermoregulatory threshold. The threshold was 35.5 +/- 0.8 degrees C during electrical stimulation and 35.1 +/- 0.6 degrees C without stimulation (P = 0.050, 95% confidence interval for the difference = 0-0.7 degree C). These data suggest that thresholds determined in nonsurgical volunteers will be slightly (but not clinically significantly) less than those in operative patients. Similarly, intraoperative vasoconstriction thresholds likely will be slightly less when surgical pain is prevented by simultaneous regional or local analgesia.     

Sweating threshold during isoflurane anesthesia in humans

Isoflurane anesthesia in humans markedly decreases the threshold temperature triggering peripheral thermoregulatory vasoconstriction (i.e., central temperature triggering vasoconstriction). However, it is not known whether the sweating threshold remains unchanged (e.g., near 37 degrees C), decreases along with the vasoconstriction threshold, or increases during anesthetic administration. Accordingly, the hypothesis that isoflurane anesthesia increases the thermoregulatory threshold for sweating was tested. Forehead sweating was evaluated in five healthy patients given isoflurane anesthesia. The sweating threshold was prospectively defined as the distal esophageal temperature at which significant sweating was first observed. Sweating was observed in each patient at a mean central temperature of 38.3 +/- 0.3 degrees C and an end-tidal isoflurane concentration of 1.1% +/- 0.2%. The interthreshold range (difference between vasoconstriction and sweating thresholds) without anesthesia is approximately 0.5 degrees C; isoflurane anesthesia increases this range to approximately 4 degrees C.     

Vecuronium infusion dose requirements during fentanyl and halothane anesthesia in humans

Steady-state infusion rate requirements of vecuronium were determined in 29 patients during either halothane-nitrous oxide or fentanyl-nitrous oxide anesthesia at different levels of neuromuscular block. During N2O-halothane anesthesia (end-tidal concentration, 0.5%), the infusion rate necessary for a steady-state (defined as unchanging twitch height and infusion rate for at least 20 min) 50% depression of twitch force was 28.8 +/- 5.4 (mean +/- SD) (n = 8) and 47.6 +/- 9.7 micrograms . kg-1 . hr-1 (n = 6) at 90% reduction of twitch force. During N2O-fentanyl anesthesia, the steady-state infusion rate required for 50 and 90% decrease of twitch force was 56.3 +/- 20.0 (n = 9) and 74.8 +/- 16.0 micrograms . kg-1 . hr-1 (n = 6), respectively. The variances of vecuronium steady-state infusion dose requirements were smaller in the halothane groups than in the fentanyl anesthesia groups. The steady-state vecuronium infusion dose requirements during fentanyl anesthesia were greater than the mean infusion dose requirements during halothane anesthesia at equivalent levels of twitch depression.     

Antiarrhythmic effect of diltiazem during halothane anesthesia in dogs and in humans

The antiarrhythmic effects of diltiazem (DL), a slow channel inhibitor, were evaluated in the presence of epinephrine-halothane-induced arrhythmias in dogs, of premature ventricular contractions (PVCs) during anesthesia in patients (n = 10), and of tachyarrhythmias with associated atrial fibrillation (AF) during anesthesia in patients (n = 9). The arrhythmogenic dose of epinephrine (ADE) during one MAC of halothane in dogs was increased from 1.13 +/- 0.21 to 3.14 +/- 0.89 microgram X kg-1 X min-1 by the administration of 0.3 mg/kg of DL. This suggests that DL significantly increases the threshold for the induction of arrhythmias associated with epinephrine and halothane. In 10 patients, PVCs that appeared spontaneously during halothane anesthesia were eliminated by the intravenous administration of DL (0.1 mg/kg). With an additional nine patients who had had AF preoperatively and suffered tachyarrhythmias during anesthesia, the intraoperative intravenous administration of DL significantly decreased heart rate (to less than 100 beats/min) within 10-15 min. Diltiazem is an effective means for the treatment of PVCs and AF-mediated tachyarrhythmias during anesthesia. Because of the pharmacologic properties of DL (e.g., depressing sinus and atrioventricular (AV) node function), DL should be used with caution in patients with a sick sinus syndrome or an AV block, or in the presence of beta-adrenergic antagonists.     

Vecuronium-induced neuromuscular blockade during enflurane, isoflurane, and halothane anesthesia in humans

To determine the effect of the commonly used volatile anesthetics on a vecuronium-induced neuromuscular blockade, the authors studied 54 patients anesthetized with 1.2 MAC or 2.2 MAC enflurane, isoflurane, or halothane (MAC value includes contribution from 60% nitrous oxide). During 1.2 MAC enflurane, isoflurane, and halothane, the ED50S (the doses depressing twitch tension 50%) for vecuronium were 12.8, 14.7, and 16.9 micrograms/kg, respectively. During 2.2 MAC enflurane, isoflurane, and halothane, the ED50S for vecuronium were 6.3, 9.8, and 13.8 micrograms/kg, respectively (P less than 0.05). Time from injection to peak effect was the same for each anesthetic group (6.5 +/- 0.5 min, mean +/- SD), except for the group given 2.2 MAC enflurane (9.7 +/- 0.6 min) (P less than 0.05). The duration of a 50% block from injection to 90% recovery was the same for each group (mean 20 +/- 4 min), except for the group given 2.2 MAC enflurane (46.5 min) (P less than 0.05). The authors conclude that enflurane is the most potent volatile anesthetic, followed by isoflurane and then halothane, in augmenting a vecuronium-induced neuromuscular blockade. Increasing the concentration of volatile anesthetic has less effect on a neuromuscular blockade produced by vecuronium than on one produced by other nondepolarizing relaxants (e.g., pancuronium and d-tubucurarine).     

Lack of the mechanoreceptor influences on ventilatory control during halothane anesthesia in humans

Mechanical influences independent of chemoreceptor function on ventilatory control were studied in halothane-anesthetized, artificially ventilated patients using the technique reported by Altose et al. (Respir Physiol 66: 171–180, 1986). Contribution of mechanical factor was indirectly assessed by comparing the values of arterial carbon dioxide tension at which the subjects started breathing efforts during CO₂ loading induced by the following two methods. 1) Partial rebreathing of expired gas and 2) Mechanical hypoventilation (successive decrease in inflation volume). These two maneuvers resulted in a similar rate of increase in end-expiratory carbon dioxide tension. However, contrary to the observation made by Altose et al. in awake volunteers, we found comparable values of ventilatory recruitment threshold for Pa_{CO 2}. Thus, we speculate that halothane anesthesia and/or loss of consciousness impair transmission of afferent information from the lung and/or chest wall musculature. Such effects may be responsible for the depression of load compensatory mechanism during anesthesia.(Kochi T, Ide T, Isono S, et al.: Lack of the mechanoreceptor influences on ventilatory control during halothane anesthesia in humans. J Anesth 6: 387–394, 1992)     

Ventilatory compensation for continuous inspiratory resistive and elastic loads during halothane anesthesia in humans

Inspiratory mechanical loads were applied to the airway continuously for 5 min in healthy young adult volunteers maintained in a near steady-state of halothane anesthesia 1.1 MAC. The loads, both flow resistive and elastic in nature, had been selected to reduce the first loaded tidal volume approximately 10, 30 or 50%--these being designated "small," "medium," and "large" loads, respectively. The actual magnitudes of resistive load were 8 +/- 1, 21 +/- 3, and 48 +/- 6 cmH2O X l-1 X s, and of elastic load 6 +/- 1, 18 +/- 1, and 41 +/- 5 cmH2O X l-1 (mean +/- SEM). All loads caused an immediate reduction of ventilation proportional to the size of the load. This was followed by a gradual recovery of ventilation toward control values over approximately 2 min and then nearly stable ventilation for the rest of the loading period. Respiratory frequency was unchanged throughout. At 5 min of loading, ventilation and PaCO2 had been nearly steady for 3 min and O2 uptake and CO2 output at the airway were unchanged from control, suggesting the establishment of a near steady respiratory state. With the small and medium loads of both types, ventilation and PaCO2 in this near steady-state were not detectably different from control. With the large loads, however, ventilation was significantly reduced and PaCO2 slightly increased. The end-expiratory position of the chest wall and the relative contributions of the rib cage and abdomen-diaphragm to ventilation, as estimated by anteroposterior chest wall magnetometers, were not consistently altered by any load.(ABSTRACT TRUNCATED AT 250 WORDS)     

The threshold and gain of thermoregulatory vasoconstriction differs during anesthesia in the dependent and upper arms in the lateral position

Increased intraluminal pressure may help maintain vasodilation in a dependent arm even after hypothermia triggers centrally mediated thermoregulatory vasoconstriction. We therefore tested the hypotheses that the threshold (triggering core temperature) and gain (increase in vasoconstriction per degree centigrade) of cold-induced vasoconstriction is reduced in the dependent arm during anesthesia. Anesthesia was maintained with 0.4 minimum alveolar anesthetic concentration of desflurane in 10 volunteers in the left-lateral position. Mean skin temperature was reduced to 31 degrees C to decrease core body temperature. Fingertip blood flow in both arms was measured, as was core body temperature.The vasoconstriction threshold was slightly, but significantly, less in the dependent arm (36.2 degrees C +/- 0.3 degrees C, mean +/- SD) than in the upper arm (36.5 degrees C +/- 0.3 degrees C). However, the gain of vasoconstriction in the dependent arm was 2.3-fold greater than in the upper arm. Consequently, intense vasoconstriction (i.e., a fingertip blood flow of 0.15 mL/min) occurred at similar core temperatures. In the lateral position, the vasoconstriction threshold was reduced in the dependent arm; however, gain was also increased in the dependent arm. The thermoregulatory system may thus recognize that hydrostatic forces reduce the vasoconstriction threshold and may compensate by sufficiently augmenting gain. IMPLICATIONS: The threshold for cold-induced vasoconstriction is reduced in the dependent arm, but the gain of vasoconstriction is increased. Consequently, the core temperature triggering intense vasoconstriction was similar in each arm, suggesting that the thermoregulatory system compensates for the hydrostatic effects of the lateral position.     

Magnesium deficiency alters the threshold for epinephrine-induced arrhythmias during halothane or sevoflurane anesthesia in the rat

OBJECTIVE: To determine the effect of chronic magnesium (Mg2+) deficiency on the relative arrhythmogenicity of halothane and sevoflurane in the rat. DESIGN: Prospective, randomized, nonblinded study. SETTING: University laboratory. PARTICIPANTS: Male Sprague-Dawley rats (n = 48). INTERVENTIONS: Rats were maintained on a Mg2+-deficient or control diet for 14 days, at which time they were anesthetized with halothane or sevoflurane, a tracheostomy was performed, and the lungs were ventilated to maintain normocapnia. Catheters were inserted into a femoral vein and carotid artery. Lead II of the electrocardiogram was monitored to determine the threshold for epinephrine-induced arrhythmias. MEASUREMENTS AND MAIN RESULTS: Chronic Mg2+ deficiency significantly decreased the dose of epinephrine required for arrhythmias (ADE). The reduction in the ADE was approximately one third during halothane anesthesia (p < 0.05) and one fifth during sevoflurane anesthesia (p < 0.001). Infusion of magnesium sulphate completely reversed the reduction in ADE. In normomagnesemic rats, the halothane ADE was significantly less than the sevoflurane ADE (mean difference = 6.0 microg/kg, 95% confidence interval of the difference = 3.6 to 8.4 microg/kg) (p < 0.005). Mg2+ deficiency significantly attenuated the difference between the halothane ADE and the sevoflurane ADE (mean difference in the Mg2+-deficient group = 0.6 microg/kg, 95% confidence interval of the difference = -0.2 to 1.5 microg/kg). CONCLUSION: Chronic Mg2+ deficiency decreased the threshold for epinephrine-induced arrhythmias and attenuated differences between the arrhythmogenic potential of halothane and sevoflurane, suggesting that arrhythmias are as likely to develop with sevoflurane as with halothane in the presence of coexisting magnesium deficiency and elevated catecholamines.     

Functional brain imaging during anesthesia in humans: effects of halothane on global and regional cerebral glucose metabolism

BACKGROUND: Propofol and isoflurane anesthesia were studied previously with functional brain imaging in humans to begin identifying key brain areas involved with mediating anesthetic-induced unconsciousness. The authors describe an additional positron emission tomography study of halothane's in vivo cerebral metabolic effects. METHODS: Five male volunteers each underwent two positron emission tomography scans. One scan assessed awake-baseline metabolism, and the other scan assessed metabolism during halothane anesthesia titrated to the point of unresponsiveness (mean +/- SD, expired = 0.7+/-0.2%). Scans were obtained using a GE2048 scanner and the F-18 fluorodeoxyglucose technique. Regions of interest were analyzed for changes in both absolute and relative glucose metabolism. In addition, relative changes in metabolism were evaluated using statistical parametric mapping. RESULTS: Awake whole-brain metabolism averaged 6.3+/-1.2 mg x 100 g(-1) x min(-1) (mean +/- SD). Halothane reduced metabolism 40+/-9% to 3.7+/-0.6 mg x 100 g(-1) x min(-1) (P< or =0.005). Regional metabolism did not increase in any brain areas for any volunteer. The statistical parametric mapping analysis revealed significantly less relative metabolism in the basal forebrain, thalamus, limbic system, cerebellum, and occiput during halothane anesthesia. CONCLUSIONS: Halothane caused a global whole-brain metabolic reduction with significant shifts in regional metabolism. Comparisons with previous studies reveal similar absolute and relative metabolic effects for halothane and isoflurane. Propofol, however, was associated with larger absolute metabolic reductions, suppression of relative cortical metabolism more than either inhalational agent, and significantly less suppression of relative basal ganglia and midbrain metabolism.     

The hemodynamic and metabolic changes following tourniquet release during halothane anesthesia

We measured the hemodynamic and metabolic changes following the release of lower limb tourniquet during halothane anesthesia, and discussed the cause of reduction in the blood pressure and the effective method for prevention. Cardiac index decreased transiently following the release, and gradually increased afterward. Systemic vascular resistance index decreased continuously and progressively until 10 minutes after the release. These results indicate that the causative factors of reduction in the blood pressure are temporary decrease in cardiac output and subsequent decrease in systemic vascular resistance. In mixed venous blood, pH decreased, PCO2 increased and HCO3- remained unchanged after the release. It seems that pH reduction was chiefly caused by the increase in PO2. Thus, the preventive method for reduction in the blood pressure following the tourniquet release may be as follows; 1) intravenous fluid loading, 2) hyperventilation, 3) elevation of lower limb, 4) lightning the anesthesia, and 5) finally giving vasopressors.     

Thermoregulatory vasoconstriction during propofol/nitrous oxide anesthesia in humans: threshold and oxyhemoglobin saturation.

To determine the thermoregulatory effects of propofol and nitrous oxide, we measured the threshold for peripheral vasoconstriction in seven volunteers over a total of 13 study days. We also evaluated the effect of vasoconstriction on oxyhemoglobin saturation (SpO2). Anesthesia was induced with an intravenous bolus dose of propofol (2 mg/kg), followed by an infusion of 180 micrograms.kg-1 x min-1 for 15 min, and maintained with 60% nitrous oxide and propofol (80-160 micrograms.kg-1 x min-1). Central and skin surface temperatures and SpO2 (using two different pulse oximeters) were measured continuously; plasma propofol concentrations and arterial PO2 were measured at 15-min intervals. Volunteers were cooled with a circulating water blanket until definitive peripheral vasoconstriction was detected. The tympanic membrane temperature triggering vasoconstriction was considered the thermoregulatory threshold. Vasoconstriction developed on seven study days during propofol/nitrous oxide anesthesia at a central temperature of 33.3 +/- 1.0 degrees C (mean +/- SD) and plasma propofol concentration of 3.9 +/- 1.1 micrograms/mL. The thresholds during anesthesia were significantly lower than those during the control period (36.7 +/- 0.3 degrees C), but the correlation between plasma propofol concentrations and vasoconstriction thresholds was poor. On the remaining six study days, vasoconstriction did not develop despite central temperatures ranging from 32.1 to 32.7 degrees C. Corresponding propofol concentrations were 4.1-10.9 micrograms/mL. These data suggest that anesthesia with propofol, in typical clinical concentrations, and 60% nitrous oxide substantially inhibits thermoregulatory vasoconstriction. Vasoconstriction increased SpO2 by approximately 2% without a significant concomitant change in PO2. The observed increase in SpO2 probably reflects decreased transmission of arterial pulsations to venous blood in the finger.