The influence of gender on loss of consciousness with sevoflurane or propofol.
ABSTRACT Studies have suggested that hypnotic requirements for general anesthesia and emergence may be influenced by gender. In this study, we examined the effect of gender on the hypnotic requirement for loss of consciousness (LOC) using either a volatile (sevoflurane) or an IV (propofol) anesthetic. One-hundred-fifteen unpremedicated, ASA physical status I-II patients, aged 18-40 yr old, received either sevoflurane by mask to a predetermined end-tidal concentration (%ET(sevo)) or propofol by target-controlled infusion (effect site) while breathing spontaneously. After sufficient time for equilibration, LOC was assessed by lack of response to mild prodding. The up-down method of Dixon was used to determine the hypnotic target concentration at 50% response (LOC(50)). No statistically significant difference in LOC(50) was noted between men and women for sevoflurane (0.83% +/- 0.1% and 0.92% +/- 0.09% ET, respectively). Men required significantly more propofol than women (2.9 +/- 0.2 versus 2.7 +/- 0.1 microg/mL, respectively). However, there was no difference in the bispectral index (BIS) at LOC for men or women with either hypnotic anesthetic. This investigation identified a small, statistically significant difference in hypnotic requirement at LOC(50) between men and women with propofol but not with sevoflurane. As defined by BIS, men and women had equivalent hypnotic states at LOC(50), indicating that gender had no clinically significant effect on hypnotic requirements. However, BIS at a defined clinical end-point (LOC(50)) was significantly different between the sevoflurane and propofol groups, suggesting that neurophysiological effects of these anesthetics may be different. IMPLICATIONS: Gender affects the dosing requirements for, and response to, many drugs used in anesthetic practice. Loss of consciousness is an early clinical marker of hypnotic drug effect. We found no significant difference to either an inhaled (sevoflurane) or IV (propofol) anesthetic related to patient gender.
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ABSTRACT: Because propofol is water insoluble, current formulations of propofol use a soybean oil emulsion. These soybean emulsions cause elevated plasma triglycerides and support bacterial growth. This study compares an alternative formulation of propofol as a 2% emulsion in a medium-chain triglyceride solution (IDD-D Propofol) with Diprivan. This double-blind, crossover, phase 1 study compared IDD-D Propofol with Diprivan using two consecutive protocols of 12 subjects each. Subjects in protocol 1 received a single bolus of 2.5 mg/kg, and those in protocol 2 received the same induction dose followed by a 30-min infusion at 0.2 mg. kg(-1).min(-1). Venous samples were taken for propofol concentration and biochemical measurements. Induction and emergence times were measured by termination of voluntary counting and responding to command, respectively. Plasma concentrations were not different between the two formulations. Induction time was 14% longer with IDD-D Propofol than with Diprivan (N = 24, protocols 1 and 2 combined, 53.3 +/- 12.1 s and 46.9 +/- 7.8 s, respectively; P = 0.002). Emergence time was not significantly different for protocol 1 but was marginally longer (P = 0.04) for IDD-D Propofol in protocol 2 (1,197 +/- 445 s [n = 11] and 1,254 +/- 468 s [n = 12], respectively). As expected because of the inherent characteristics of the formulations, plasma triglycerides were elevated for Diprivan but not for IDD-D Propofol; octanoate, a metabolite of medium-chain triglycerides, was elevated only with IDD-D Propofol. Octanoate was elevated to concentrations below those considered toxic. Plasma concentrations of other biochemical markers of medium-chain triglyceride metabolism, ketones, showed no significant changes. Interestingly, there were significant differences between male and female subjects in the propofol plasma concentrations and time to awakening with both drugs. Differences between the two propofol formulations were slight and not clinically significant. Similar gender differences in plasma concentrations and awaking times were found for both formulations.Anesthesiology 01/2003; 97(6):1401-8. · 5.16 Impact Factor
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ABSTRACT: The bispectral index (BIS), a value derived from the electroencephalograph (EEG), has been proposed as a measure of anesthetic effect. To establish its utility for this purpose, it is important to determine the relation among BIS, measured drug concentration, and increasing levels of sedation. This study was designed to evaluate this relation for four commonly used anesthetic drugs: propofol, midazolam, isoflurane, and alfentanil. Seventy-two consenting volunteers were studied at four institutions. Volunteers were given either isoflurane, propofol, midazolam, or alfentanil. Each volunteer was administered a dose-ranging sequence of one of the study drugs to achieve predetermined target concentrations. A frontal montage was used for continuous recording of the EEG. At each pseudo-steady-state drug concentration, a BIS score was recorded, the participant was shown either a picture or given a word to recall, an arterial blood sample was obtained for subsequent analysis of drug concentration, and the participant was evaluated for level of sedation as determined by the responsiveness portion of the observer's assessment of the alertness/ sedation scale (OAAS). An OAAS score of 2 or less was considered unconscious. The BIS (version 2.5) score was recorded in real-time and the BIS (version 3.0) was subsequently derived off-line from the recorded raw EEG data. The relation among BIS, measured drug concentration, responsiveness score, and presence or absence of recall was determined by linear and logistic regression for both the individual drugs and, when appropriate, for the pooled results. The prediction probability was also calculated. The BIS score (r = 0.883) correlated significantly better than the measured propofol concentration (r = -0.778; P < 0.05) with the responsiveness score. The BIS provided as effective correlation with responsiveness score of the OAAS as did the measured concentration for midazolam and isoflurane. None of the volunteers given alfentanil lost consciousness and thus were excluded from the pooled analysis. The pooled BIS values at which 50% and 95% of participants were unconscious were 67 and 50, respectively. The prediction probability values for BIS ranged from 0.885-0.976, indicating a very high predictive performance for correctly indicating probability of loss of consciousness. The BIS both correlated well with the level of responsiveness and provided an excellent prediction of the loss of consciousness. These results imply that BIS may be a valuable monitor of the level of sedation and loss of consciousness for propofol, midazolam, and isoflurane.Anesthesiology 05/1997; 86(4):836-47. · 5.16 Impact Factor
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ABSTRACT: Differences in the pharmacokinetics of propofol between male and female patients during and after continuous infusion have not been described in detail in patients aged 65 yr and older. To increase our insight into the pharmacokinetics of propofol in this patient population and to obtain pharmacokinetic parameters applicable in target controlled infusion (TCI), the pharmacokinetics of propofol during and after continuous infusion were studied in 31 ASA class 1 and 2 patients, aged 65-91 yr, scheduled for general surgery. Patients received propofol 1.5 mg kg(-1) i.v. in 1 min followed by 7 mg kg(-1) h(-1) until skin closure in the presence of a variable rate infusion of alfentanil during oxygen-air ventilation. On the basis of arterial blood samples that were taken up to 24 h post-infusion, the pharmacokinetics of propofol were evaluated in a two-stage manner. Multiple linear regression analysis was used to explore the effect of age, weight, gender and lean body mass as covariates. Gender significantly affected the pharmacokinetics of propofol. V3, Cl1 and Cl2 were significantly different between male and female patients, weight only affected Cl1. The pharmacokinetic parameters were: V1=4.88 litre, V2=24.50 litre, V3 (litre)=115+147 x gender (gender: male=1, female=2), Cl1 (litre min(-1))=-0.29+0.022 x weight+0.22 x gender, Cl2 (litre min(-1))=2.84-0.65 x gender (male=1, female=2), and Cl3=0.788 litre min(-1).BJA British Journal of Anaesthesia 03/2001; 86(2):183-8. · 4.24 Impact Factor