In a randomised controlled trial, preterm babies undergoing ligation of a patent ductus arteriosus were given nitrous oxide and d-tubocurarine, with (n = 8) or without (n = 8) the addition of fentanyl (10 micrograms/kg intravenously) to the anaesthetic regimen. Major hormonal responses to surgery, as indicated by changes in plasma adrenaline, noradrenaline, glucagon, aldosterone, corticosterone, 11-deoxycorticosterone, and 11-deoxycortisol levels, in the insulin/glucagon, molar ratio, and in blood glucose, lactate, and pyruvate concentrations were significantly greater in the non-fentanyl than in the fentanyl group. The urinary 3-methylhistidine/creatinine ratios were significantly greater in the non-fentanyl group on the second and third postoperative days. Compared with the fentanyl group, the non-fentanyl group had circulatory and metabolic complications postoperatively. The findings indicate that preterm babies mount a substantial stress response to surgery under anaesthesia with nitrous oxide and curare and that prevention of this response by fentanyl anaesthesia may be associated with an improved postoperative outcome.

Fentanyl, alfentanil, and sufentanil have important pharmacokinetic and pharmacodynamic differences. Selecting one of these opioid analgesics as an adjunct to general anesthesia requires appreciation of the relationship between the pharmacokinetic and pharmacodynamic characteristics of these drugs and the onset of and recovery from drug effect. Using a pharmacokinetic-pharmacodynamic model, the authors simulated the decrease in plasma fentanyl, alfentanil, and sufentanil concentration after intravenous administration by either bolus injection, brief infusion, or prolonged infusion. The percentage change in concentration, rather than absolute concentration, was simulated to permit comparison of the relative opioid concentration independently of drug potency. These computer simulations quantified the relationship between infusion duration and the time required for recovery after termination of the infusion. The analysis suggests that alfentanil is best used for operations longer than 6-8 h when a rapid decrease in effect site (i.e., biophase) opioid concentration is desired after discontinuation of the infusion. Alfentanil may also be the most appropriate drug to provide a transient peak effect after a single bolus. Although sufentanil has longer distribution and elimination half-lives than alfentanil, recovery from sufentanil infusions may be more rapid than recovery from alfentanil infusions for operations shorter than 6-8 h. These computer simulations demonstrate that simply comparing pharmacokinetic parameters (e.g., half-lives) of different drugs will not predict the relative rates of decrease in effect site concentrations after either an intravenous bolus or a continuous infusion.

Awareness, defined as conscious memory during anesthesia, has been a problem in anesthesia practice. To determine the effect of isoflurane and nitrous oxide (N2O) on memory, 17 healthy adult volunteers were randomly assigned to receive isoflurane or N2O and received the alternate agent 1-2 weeks later. Each volunteer was studied at four end-tidal concentrations of each agent, consecutively 0.15, 0.3, 0.45, and 0.15 times the minimum alveolar concentration (MAC) for isoflurane or 0.3, 0.45, 0.6, and 0.3 times MAC for N2O. After 15-min equilibration at each end-tidal concentration, volunteers were tested for voluntary response to command and were presented with verbal information to be recalled after anesthesia. Volunteers were interviewed on the day after the study and tested for conscious and unconscious memory of the information presented during anesthetic administration. MAC-awake (the end-tidal concentration preventing voluntary response in 50% of volunteers) was 0.38 (0.35-0.42) times MAC for isoflurane and 0.64 (0.61-0.68) MAC for N2O (means, 95% confidence limits), indicating isoflurane to be more potent than N2O in suppressing voluntary response (P =.0001). Memory data were analyzed in 12 volunteers who completed the study and in whom the allocation of information to be recalled was counterbalanced among agents and concentrations of agents. Memory was decreased by increasing concentrations of both agents. Conscious memory of the information presented during anesthetic administration was prevented by 0.45 MAC isoflurane but not completely prevented by 0.6 MAC N2O. Unconscious memory (defined as memory of information without conscious recognition) occurred during administration of both agents and was prevented by 0.45 MAC isoflurane but not by 0.6 MAC N2O. Isoflurane was more potent in suppressing memory than MAC-equivalent concentrations of N2O. Using models of the relationship between dose of agent and suppression of memory, a dose of both agents was estimated that suppressed memory by 50%(ED50). The ED50 was 0.20 MAC for isoflurane (95% confidence intervals, 0.15-0.25), and 0.50 MAC for N2O (95% confidence intervals 0.43-0.55). We conclude that isoflurane and N2O suppress memory in a dose-dependent manner, and that isoflurane is more potent in preventing memory and voluntary response to command than MAC-equivalent concentrations of N2O.

We evaluated the effect of dexamethasone on vomiting after elective tonsillectomy in 133 healthy children aged 2-12 yr in a randomized, stratified, blocked, double-blind, placebo-controlled study. General anesthesia was induced by inhalation of N2O and halothane or intravenously (IV) with propofol. Anesthesia was maintained with N2O and halothane. Dexamethasone 150 micrograms/kg up to a maximum dose of 8 mg, or placebo, was administered IV before surgery. All patients received 1.5 mg/kg codeine intramuscularly (IM) intraoperatively. Perioperative IV fluids, management of emesis, postoperative pain and hospital discharge criteria were all standardized. The groups were similar with respect to number, age, weight, length of surgery, and estimated intraoperative blood loss. Dexamethasone reduced the overall incidence of vomiting from 72%(placebo) to 40%(P < 0.001). Vomiting, both in-hospital and postdischarge, was decreased by the prophylactic administration of dexamethasone. Each episode of in-hospital vomiting prolonged discharge by 13 +/- 2 min, mean +/- SD (P < 0.001). In conclusion, dexamethasone markedly decreased vomiting by healthy children after elective tonsillectomy in an ambulatory hospital setting.

The latency of the early cortical wave Nb of the auditory evoked response (AER) was compared with responses to Tunstall's isolated forearm test, while the concentration of nitrous oxide was progressively reduced during light anaesthesia in seven patients. A threshold Nb latency of 44.5 ms was chosen to discriminate between an early cortical AER containing three waves and that with two waves of longer latency. When Nb latency decreased below this threshold, four of the patients has positive responses, indicating awareness. The addition of a volatile anaesthetic abolished any response, and increased Nb latency to more than 44.5 ms. The three wave AER pattern, therefore, is associated with a depth of anaesthesia at which awareness occurs.

The potency and anesthetic state produced by nitrous oxide alone were investigated in order to clarify its contribution to the effect of other anesthetic agents. Seven volunteers anesthetized with 1.55 atm absolute N2O in a pressure chamber displayed muscle rigidity with jerking movements, labored and rapid breathing, sweating, and dilated pupils. At 1.1 atm absolute N2O, relaxation and quiescence occurred, sweating ceased, and pupil size decreased. Determination of MAC (using tetanic electrical impulses as the noxious stimulus) produced a mean value of 1.04 +/- 0.10 (SE) atm absolute. All subjects complained of nausea and vomiting after anesthesia.

The effects of various plasma concentrations of lidocaine on nitrous oxide anesthesia in man and halothane requirements in the dog were studied. The response to incision of the skin was observed in 20 patients who were anesthetized with nitrous oxide, 70% inspired, and oxygen, 30%, plus various plasma levels of lidocaine. In addition, changes in the MAC of halothane in dogs were observed at various levels of lidocaine. In both circumstances lidocaine concentrations of 3 to 6 microgram/ml decreased anesthetic requirements approximately 10 to 28%. At clinically common concentrations of lidocaine, significant decreases in anesthetic requirements should be anticipated.

The utility of bispectral index (BIS) monitoring to guide anesthetic administration has been demonstrated in adults. This prospective, randomized observer-blinded study was designed to evaluate the effect of BIS monitoring on anesthetic use and recovery characteristics in pediatric patients. After data collection in 38 historical controls, 202 patients age 0-18 yr were randomized into one of two groups: standard practice (SP) and BIS guided (BIS). Patients age 0-3 yr undergoing inguinal hernia repair (IH) and patients age 3-18 yr undergoing tonsillectomy and/or adenoidectomy (TA) were selected. All patients were anesthetized with sevoflurane in 60% N(2)O/O(2). Hernia patients also received a caudal epidural anesthetic before surgery. In the BIS group, anesthetic delivery was adjusted in an effort to achieve a target BIS of 45-60 during maintenance and 60-70 during the last 15 min of the procedure. BIS was recorded throughout surgery in all patients, but data were unavailable to the anesthesiologist in the SP group. In the TA patients, BIS monitoring was associated with a significant reduction in end-tidal sevoflurane concentration during maintenance (2.4 +/- 0.6%, SP and 1.8 +/- 0.4% BIS, mean +/- SD) and during the last 15 min of the procedure (2.1 +/- 0.7, SP and 1.6 +/- 0.6, BIS). There was a 25%-40% decrease in measured recovery times. In the patients 0-6 mo of age undergoing IH, sevoflurane concentrations during maintenance (2.0 +/- 0.4% SP, 0.9 +/- 0.8 BIS), during the last 15 min (1.6 +/- 0.4% SP, 0.6 +/- 0.6% BIS), and at the end of the procedure (1.1 +/- 0.6% SP, 0.3 +/- 0.3% BIS) were smaller in the BIS group. Emergence and recovery measures were unaffected by BIS titration. In the children 6 mo-3 yr of age, there were no significant differences between the SP and BIS groups in anesthetic use or recovery measures. IMPLICATIONS: Bispectral index monitoring in children results in less anesthetic use and faster recovery than standard practice.

The cardiovascular effects of plasma levels of thiopental necessary for anesthesia were studied using systolic time intervals (STI). In ten healthy patients anesthesia was induced with thiopental, 2-2.5 mg/kg, intravenously, and maintained with an infusion of 1-1.5 mg/kg/min. STI and thiopental plasma levels were measured before induction and when corneal reflex and trapezius muscle response, indicators of anesthetic depth equivalent to response to surgical stimulation, were lost. Significant changes included: an increase in heart rate with induction of anesthesia; a decrease in 1/pre-ejection period2--indexed for heart rate (1/PEP2-I) at loss of corneal reflex; a decrease in systolic blood pressure and 1/PEP2-I at loss of trapezius muscle response. No other variable was significantly different from control. Control values for STI were in the high-normal range, indicating some sympathetic stimulation. With induction of anesthesia these values decreased to a normal range. Free and total plasma levels were 5.4 and 37.6 microgram/ml at loss of corneal reflex; 6.1 and 41.6 microgram/ml at loss of trapezius muscle response. In comparison with other studies, thiopental causes less cardiac depression than inhalational agents at approximately the same anesthetic depth. It is concluded from this study in healthy patients that plasma levels of thiopental producing surgical anesthesia result in minimal cardiac depression as determined by systolic time intervals.