Effect of propofol on visual evoked potentials during neurosurgery

BACKGROUND: Evoked potentials are used to monitor the central nervous system during neurosurgery and it is well known that they are affected by the depth of anesthesia. Many studies on the evoked potential like somatosensory evoked potential (SEP) and auditory brain stem response (ABR) are reported, but studies on visual evoked potential (VEP) are few. We investigated the influence of the propofol concentration on VEP in neurosurgical patients. METHODS: Seven patients scheduled for neurosurgery, three with cranial aneurysm and four with brain tumor, were studied. Anesthesia was maintained with intravenous propofol using target controlled infusion (TCI). We measured the change of amplitude and latency of VEP at three propofol concentrations (effect site concentrations of 1.5, 2.0 and 3.0 microg x ml(-1)), and also evaluated bispectral index (BIS) at each propofol concentration. RESULTS: Amplitude of VEP at 3.0 microg x ml(-1) propofol concentration decreased significantly compared with the amplitude at 1.5 microg x ml(-1) concentration. No significant change was observed with the latency of VEP. The value of BIS at 3.0 microg x ml(-1) propofol concentration also decreased significantly compared with 2.0 microg x ml(-1) concentration. CONCLUSIONS: Amplitude of VEP is strongly affected by the concentration of propofol. Caution should be taken in evaluating VEP in patients undergoing propofol anesthesia.     

Propofol suppresses the cortical somatosensory evoked potential in rats

The dose-response curve for the effect of volatile anesthetics on the somatosensory evoked potential (SEP) is well described, but for propofol, the large dose segment of the curve is undefined. We describe the effect of increasing plasma concentrations of propofol on cortical SEPs in 18 rats. After surgical preparation under ketamine anesthesia, a remifentanil infusion was begun at 2.5, 5, or 10 microg x kg(-1) x min(-1). After 20 min, the propofol infusion was initiated at 20 mg x kg(-1) x h(-1) and was increased to 40, 60, and 80 mg x kg(-1) x h(-1) at 20-min intervals. SEP was recorded before remifentanil infusion, before propofol infusion rate changes, and 30 min after discontinuing propofol infusion. In six additional rats, the plasma concentrations of propofol after each 20-min infusion were measured using gas chromatography. Remifentanil did not have a significant effect, but propofol significantly depressed the SEP amplitude and prolonged the latency at infusion rates of 40 mg x kg(-1) x h(-1) and more. Propofol's effect was dose-dependent, but even at 80 mg x kg(-1) x h(-1) with an estimated plasma concentration of 31.6 +/- 3.4 microg/mL (10.8 50% effective concentration), a measurable response was present in 44.5% of rats. These results suggest that even at large doses, propofol and remifentanil provide adequate conditions for SEP monitoring. IMPLICATIONS: Rats demonstrate dose-dependent somatosensory evoked potential (SEP) suppression with propofol but not with remifentanil. However, SEP suppression by 50% occurred only at large (1.5 EC(50)) concentrations of propofol, and a measurable SEP was present in 8 of 18 rats, even at 10.8 EC(50).     

Propofol and sevoflurane in subanesthetic concentrations act preferentially on the spinal cord: evidence from multimodal electrophysiological assessment

BACKGROUND: Animal experiments in recent years have shown that attenuation of motor responses by general anesthetics is mediated at least partly by spinal mechanisms. Less is known about the relative potency of anesthetic drugs in suppressing cortical and spinal electrophysiological responses in vivo in humans, particularly those, but not only those, connected with motor responses. Therefore, we studied the effects of sevoflurane and propofol in humans using multimodal electrophysiological assessment. METHODS: We studied nine healthy volunteers in two sessions during steady state sedation with 0.5, 1.0, and 1.5 microg/l (targeted plasma concentration) propofol or 0.2 and 0.4 vol% (end-tidal) sevoflurane. Following a 15-min equilibration period, motor responses to transcranial magnetic stimulation and peripheral (H-reflex, F-wave) stimulation were recorded, while electroencephalography and auditory evoked responses were recorded in parallel. RESULTS: At concentrations corresponding to two thirds of C(50 awake), motor responses to transcranial magnetic stimulation were reduced by approximately 50%, H-reflex amplitude was reduced by 22%, F-wave amplitude was reduced by 40%, and F-wave persistence was reduced by 25%. No significant differences between sevoflurane and propofol were found. At this concentration, the Bispectral Index was reduced by 7%, and the middle-latency auditory evoked responses were attenuated only mildly (N(b) latency increased by 11%, amplitude P(a)N(b) did not change). In contrast, the postauricular reflex was suppressed by 77%. CONCLUSIONS: The large effect of both anesthetics on all spinal motor responses, compared with the small effect on electroencephalography and middle-latency auditory evoked responses, assuming that they represent cortical modulation, may suggest that the suppression of motor responses to transcranial magnetic stimulation is largely due to submesencephalic effects.     

Respiratory reflex responses of the larynx differ between sevoflurane and propofol in pediatric patients

BACKGROUND: The effects of anesthetics on airway protective reflexes have not been extensively characterized in children. The aim of this study was to compare the laryngeal reflex responses in children anesthetized with either sevoflurane or propofol under two levels of hypnosis using the Bispectral Index score (BIS). The authors hypothesized that the incidence of apnea with laryngospasm evoked by laryngeal stimulation would not differ between sevoflurane and propofol when used in equipotent doses and that laryngeal responsiveness would be diminished with increased levels of hypnosis. METHODS: Seventy children, aged 2-6 yr, scheduled to undergo elective surgery were randomly allocated to undergo propofol or sevoflurane anesthesia while breathing spontaneously through a laryngeal mask airway. Anesthesia was titrated to achieve the assigned level of hypnosis (BIS 40 +/- 5 or BIS 60 +/- 5) in random order. Laryngeal and respiratory responses were elicited by spraying distilled water on the laryngeal mucosa, and a blinded reviewer assessed evoked responses. RESULTS: Apnea with laryngospasm occurred more often during anesthesia with sevoflurane compared with propofol independent of the level of hypnosis: episodes lasting longer than 5 s, 34% versus 19% at BIS 40 and 34% versus 16% at BIS 60; episodes lasting longer than 10 s, 26% versus 10% at BIS 40 and 26% versus 6% at BIS 60 (group differences P < 0.04 and P < 0.01, respectively). In contrast, cough and expiration reflex occurred significantly more frequently in children anesthetized with propofol. CONCLUSION: Laryngeal and respiratory reflex responses in children aged 2-6 yr were different between sevoflurane and propofol independent of the levels of hypnosis examined in this study.     

The effect of nitrous oxide on the central nervous system evaluated by the bispectral index under various levels of propofol anesthesia

BACKGROUND: The effect of nitrous oxide either as a sole agent or with volatile anesthetic agents on the central nervous system has been well studied. However, it has not been clarified during various levels of propofol anesthesia. We therefore evaluated the effect of nitrous oxide on the central nervous system using bispectral index (BIS) and suppression ratio (SR) under various levels of propofol anesthesia. METHODS: Twelve patients were enrolled for the study. After the administration of subarachnoid block, propofol was infused using a stepped down series (effect site concentration of 5, 4, 3 microg x ml(-1)) for 20 minutes. After obtaining BIS and SR at each concentration, nitrous oxide was added. RESULTS: When 67% of nitrous oxide was added to the estimated effect site propofol concentration of 5 microg x ml(-1), BIS decreased and SR increased indicating that the nitrous oxide had a depressant effect on the central nervous system. On the other hand, nitrous oxide combined with 3 or 4 microg x ml(-1) of propofol did not cause significant changes in BIS and SR, suggesting that nitrous oxide did not have a suppressive effect. CONCLUSIONS: We conclude that nitrous oxide has different effects on BIS according to their basal propofol concentrations.     

Variation of bispectral index under TIVA with propofol in a paediatric population

BACKGROUND: In this prospective observational study, we aim to explore the relationship between age and bispectral index (BIS) values at different plasma concentrations of propofol. METHODS: Fifty children aged from 3 to 15 yr were included. Anaesthesia was induced using a target-controlled infusion of propofol with the Kataria pharmacokinetic model together with a bolus of remifentanil followed by a continuous infusion rate at 0.2 microg kg(-1) min(-1). Target plasma propofol concentration was initially stabilized to 6 microg ml(-1) and continued for 6 min. The target was then decreased and stabilized to 4 microg ml(-1) and then to 2 microg ml(-1). BIS values, plasma propofol concentration, and EEG were continuously recorded. In order to explore the relationship between variations in propofol concentration and the EEG bispectrum, we used a multiple correspondence analysis (MCA). Results are shown in median (range). RESULTS: We found no statistical difference between BIS values with propofol 6 microg ml(-1) [23 (12-40)] and 4 microg ml(-1) [28 (9-67)]. At 2 microg ml(-1), BIS was significantly different [52 (24-71)], but a significant correlation between the age of children and BIS values was found (r2=0.66; P<0.01). There was little change in children's position between 6 and 4 microg ml(-1) in the structure model of the MCA. From 4 to 2 microg ml(-1), the position of children moved only on axis 2. CONCLUSIONS: These results showed the difficulty to interpret BIS values because of the absence of significant change for higher plasma propofol concentration variation or because of the link with age for the lower plasma concentration.     

The effect of two low-dose propofol infusions on the relationship between six-pulse transcranial electrical stimulation and the evoked lower extremity muscle response

BACKGROUND: Transcranial stimulation of the motor cortex using high-voltage electrical stimuli given in train is a method of monitoring the integrity of the motor pathways during thoracoabdominal aortic aneurysm surgery. The purpose of this study was to assess the relationship between the stimulus intensity and the corresponding amplitude of the myogenic motor evoked potential (tcMEP) in response to six-pulse transcranial electrical stimulation during two levels of low-dose propofol infusion and stable fentanyl/nitrous oxide anaesthesia. METHODS: Nine patients (37-78 yr) scheduled to undergo surgery on the thoracoabdominal aorta were studied. After achieving a stable anaesthetic state the output voltage was decreased with 50 V intervals from 350 V to 200 V during a target propofol infusion aimed at a plasma steady-state concentration of 0.7 microg x ml(-1) and increased with 50 V intervals from 200 V to 450 V during a target propofol infusion aimed at a plasma steady-state concentration of 1.4 microg x ml(-1). TcMEPs were recorded from the right tibialis anterior muscle. RESULTS: Doubling the target propofol infusion to 1.4 microg x ml(-1) resulted in a 30-50% decrease in tcMEP amplitude. The largest tcMEP amplitude using the six-pulse paradigm was found during a propofol infusion aimed at a plasma concentration of 0.7 microg x ml(-1) and demanded a stimulus output of 350 V, corresponding to a charge density of 7.5 microC x cm(-2) per phase. CONCLUSION: Doubling the target propofol infusion to 1.4 microg x ml(-1) provides less robust, but still recordable tcMEPs in response to six-pulse electrical stimulation. Safety guidelines are discussed.     

Interaction of propofol and sevoflurane on loss of consciousness and movement to skin incision during general anesthesia

BACKGROUND: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points. METHODS: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method. RESULTS: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 microg/ml (95% confidence interval, 1.1-1.3 microg/ml). It was not significantly different from that predicted (1.5 microg/ml; 95% confidence interval, 1.2-1.7 microg/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 microg/ml (95% confidence interval, 4.8-6.0 microg/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 microg/ml; 95% confidence interval, 4.8-5.9 microg/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not. CONCLUSIONS: Propofol and sevoflurane interact in a simple additive manner to produce LOC and immobility to surgical incision, suggesting a common mechanism or a single site of action. These clinical observations are consistent with a single site of interaction at the gamma-aminobutyric acid type A receptor.     

Respiratory Reflex Responses of the Larynx Differ between Sevoflurane and Propofol in Pediatric Patients

Background: The effects of anesthetics on airway protective reflexes have not been extensively characterized in children. The aim of this study was to compare the laryngeal reflex responses in children anesthetized with either sevoflurane or propofol under two levels of hypnosis using the Bispectral Index score (BIS). The authors hypothesized that the incidence of apnea with laryngospasm evoked by laryngeal stimulation would not differ between sevoflurane and propofol when used in equipotent doses and that laryngeal responsiveness would be diminished with increased levels of hypnosis.

Methods: Seventy children, aged 2-6 yr, scheduled to undergo elective surgery were randomly allocated to undergo propofol or sevoflurane anesthesia while breathing spontaneously through a laryngeal mask airway. Anesthesia was titrated to achieve the assigned level of hypnosis (BIS 40 +/- 5 or BIS 60 +/- 5) in random order. Laryngeal and respiratory responses were elicited by spraying distilled water on the laryngeal mucosa, and a blinded reviewer assessed evoked responses.

Results: Apnea with laryngospasm occurred more often during anesthesia with sevoflurane compared with propofol independent of the level of hypnosis: episodes lasting longer than 5 s, 34% versus 19% at BIS 40 and 34% versus 16% at BIS 60; episodes lasting longer than 10 s, 26% versus 10% at BIS 40 and 26% versus 6% at BIS 60 (group differences P < 0.04 and P < 0.01, respectively). In contrast, cough and expiration reflex occurred significantly more frequently in children anesthetized with propofol.     

Cardiac anesthesia induction by low target plasma concentration setting of propofol using target-controlled infusion

BACKGROUND: Propofol-anesthesia administerd using target-controlled infusion (TCI) has been proposed for cardiac surgery. But, moderate target concentration of propofol during induction using TCI has not been studied in detail. METHODS: Thirty patients scheduled for cardiac surgery under cardiopulmonary bypass (CPB) and TCI propofol anesthesia were randomly divided into two groups to receive a computer-controlled infusion of propofol with target concentrations of 1.5 or 2.0 micro/g x ml(-1) [1.5 microg x ml(-1) group (n=15) and 2.0 microg x ml(-1) group (n=15)]. Mean arterial pressure (MAP), heart rate (HR) and bispectral index scale (BIS) values were recorded at 5 time points during induction of anesthesia. RESULTS: MAP was significantly lower in 2.0 microg x ml(-1) group compared with 1.5 microg x ml(-1) group. In both groups, a rise of BIS value did not occur during tracheal intubation. CONCLUSIONS: We have demonstrated that propofol TCI at a target concentration of 1.5 microg x ml(-1) is effective for hemodynamic stability during induction of anesthesia in patients for cardiac surgery under CPB.     

Epidural lidocaine decreases sevoflurane requirement for adequate depth of anesthesia as measured by the Bispectral Index monitor

BACKGROUND: Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS). METHODS: After premedication with 0.02 mg/kg midazolam and 1 microg/kg fentanyl, 30 patients aged 20-65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 microg x kg(-1) x min(-1)). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up-down methodology based on BIS less than 50 (MAC(BIS50)). Plasma lidocaine concentrations were measured. RESULTS: The MAC(BIS50) of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1%; P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 microg/ml) were similar to those in the epidural lidocaine group (2.0 microg/ml). CONCLUSIONS: Epidural anesthesia reduced by 34% the sevoflurane required for adequate depth of anesthesia. This effect was not a result of systemic lidocaine absorbtion, but may have been caused by deafferentation by epidural anesthesia or direct rostral spread of local anesthetic within the cerebrospinal fluid. Lower-than-expected concentrations of volatile agents may be sufficient during combined epidural-general anesthesia.     

Changes of bispectral index during recovery from general anesthesia with 2% propofol and remifentanil in children

BACKGROUND: The bispectral (BIS) index is a pharmacodynamic measure of the effect of anesthesia on the central nervous system. The aim of this study was to investigate the relationship between BIS index and predicted plasma concentration of propofol delivered by target controlled infusion (TCI) during emergence in children. METHODS: With approval of IRB, 30 patients (2-7 years) were included in this study. Anesthesia was with TCI propofol 3-5 microg.ml(-1) and remifentanil 7.5 ng.ml(-1) to maintain BIS 40-60 and the propofol concentration was fixed at 3 microg.ml(-1) Remifentanil infusion was stopped 10 min before the end of surgery. BIS values were recorded after reducing propofol in decrement of 0.2 microg.ml(-1). BIS values were checked when spontaneous respiration occurred and children were able to obey a command (eye opening or hand grasping). RESULTS: Spearman's correlation analysis showed negative correlation between BIS and propofol plasma concentration (r = -0.559, P < 0.001). When respiration returned, mean BIS was 77.2 +/- 5.3 and propofol plasma concentration 1.6 +/- 0.3 microg.ml(-1) and when a verbal command was obeyed, BIS was 82.4 +/- 5.6 and propofol plasma concentration 1.5 +/- 0.3 microg.ml(-1). CONCLUSIONS: In preschool children, BIS moderately correlated with the predicted plasma concentration of propofol.     

The influence of gender on loss of consciousness with sevoflurane or propofol

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.     

Propofol and Sevoflurane in Subanesthetic Concentrations Act Preferentially on the Spinal Cord: Evidence from Multimodal Electrophysiological Assessment

Background: Animal experiments in recent years have shown that attenuation of motor responses by general anesthetics is mediated at least partly by spinal mechanisms. Less is known about the relative potency of anesthetic drugs in suppressing cortical and spinal electrophysiological responses in vivo in humans, particularly those, but not only those, connected with motor responses. Therefore, we studied the effects of sevoflurane and propofol in humans using multimodal electrophysiological assessment.

Methods: We studied nine healthy volunteers in two sessions during steady state sedation with 0.5, 1.0, and 1.5 [mu]g/l (targeted plasma concentration) propofol or 0.2 and 0.4 vol% (end-tidal) sevoflurane. Following a 15-min equilibration period, motor responses to transcranial magnetic stimulation and peripheral (H-reflex, F-wave) stimulation were recorded, while electroencephalography and auditory evoked responses were recorded in parallel.

Results: At concentrations corresponding to two thirds of C50 awake, motor responses to transcranial magnetic stimulation were reduced by approximately 50%, H-reflex amplitude was reduced by 22%, F-wave amplitude was reduced by 40%, and F-wave persistence was reduced by 25%. No significant differences between sevoflurane and propofol were found. At this concentration, the Bispectral Index was reduced by 7%, and the middle-latency auditory evoked responses were attenuated only mildly (Nb latency increased by 11%, amplitude PaNb did not change). In contrast, the postauricular reflex was suppressed by 77%.     

Noxious stimuli do not modify myogenic motor evoked potentials by electrical stimulation during anesthesia with propofol-based anesthesia

PURPOSE: To investigate whether motor evoked potentials (MEP) to transcranial electrical stimulation under constant blood propofol concentration are affected by the arousing effect of surgical noxious stimuli. METHODS: Twenty patients who underwent elective spinal surgery were studied. Patients were anesthetized with 50% nitrous oxide in oxygen, fentanyl, and propofol to maintain the bispectral index (BIS) score around 50. MEP in response to a multipulse transcranial electrical stimulation at stimulus sites of C3-C4 were recorded over the right abductor pollicis brevis muscle. Changes of peak-to-peak amplitude and onset latency of MEP, BIS score before and after surgical stimuli were evaluated. Propofol plasma concentration was measured at the same time points. RESULTS: Both MEP amplitude and latency did not change significantly after surgical stimuli although BIS increased significantly (48 +/- 6 to 58 +/- 5; P < 0.05). Plasma propofol concentration was maintained at the same level between the two measurement points (3.3 +/- 0.7 to 3.3 +/- 0.7 micro g*mL(-1)). There was no relation between BIS change and changes of MEP amplitude and latency, and propofol plasma concentration. CONCLUSION: MEP to the transcranial electrical stimulation under a constant and clinically appropriate blood propofol concentration are not affected by surgical noxious stimuli.     

Anesthetic management with propofol during pheochromocytoma resection under bispectral index monitoring

In three patients undergoing pheochromocytoma resection under propofol/fentanyl anesthesia, bispectral index (BIS) was monitored for assessment of hypnotic effect. In two patients, arterial blood concentrations of propofol were measured by high performance liquid chromatography (HPLC), and compared with those of the estimated blood concentrations. Until resection of the tumor, propofol was infused at a rate of 10 mg x kg(-1) x hr(-1). After resection of the tumor, propofol dosage was reduced to 3-6 mg x kg(-1) x hr(-1), keeping the BIS values around 60. Rapid infusion of fluid and norepinephrine was required to maintain blood pressure after removal of the tumor in two patients. In one patient, blood pressure was maintained well without rapid infusion of fluid or vasopressor. Arterial blood concentration of propofol after resection of the tumor was equal to the estimated blood concentration (3.04 vs 3.02 microg x ml(-1)) in a patient without rapid infusion of fluid. In a patient with rapid infusion of fluid, the arterial blood concentration was lower than the estimated blood concentration (2.59 vs 3.58 microg x ml(-1)). The anesthetic depth can not be estimated accurately by hemodynamic changes in the patients undergoing pheochromocytoma resection. BIS monitoring should be recommended for adjustment of propofol dosage after pheochromocytoma resection.     

Effects of sevoflurane,propofol, and adjunct nitrous oxide on regional cerebral blood flow,oxygen consumption,and blood volume in humans

BACKGROUND: Anesthetic agents, especially volatile anesthetics and nitrous oxide (N2O), are suspected to perturb cerebral homeostasis and vascular reactivity. The authors quantified the effects of sevoflurane and propofol as sole anesthetics and in combination with N2O on regional cerebral blood flow (rCBF), metabolic rate of oxygen (rCMRO2), and blood volume (rCBV) in the living human brain using positron emission tomography. METHODS: 15O-labeled water, oxygen, and carbon monoxide were used as positron emission tomography tracers to determine rCBF, rCMRO2 and rCBV, respectively, in eight healthy male subjects during the awake state (baseline) and at four different anesthetic regimens: (1) sevoflurane alone, (2) sevoflurane plus 70% N2O (S+N), (3) propofol alone, and (4) propofol plus 70% N2O (P+N). Sevoflurane and propofol were titrated to keep a constant hypnotic depth (Bispectral Index 40) throughout anesthesia. End-tidal carbon dioxide was strictly kept at preinduction level. RESULTS: The mean +/- SD end-tidal concentration of sevoflurane was 1.5 +/- 0.3% during sevoflurane alone and 1.2 +/- 0.3% during S+N (P < 0.001). The measured propofol concentration was 3.7 +/- 0.7 microg/ml during propofol alone and 3.5 +/- 0.7 microg/ml during P+N (not significant). Sevoflurane alone decreased rCBF in some (to 73-80% of baseline, P < 0.01), and propofol in all brain structures (to 53-70%, P < 0.001). Only propofol reduced also rCBV (in the cortex and cerebellum to 83-86% of baseline, P < 0.05). Both sevoflurane and propofol similarly reduced rCMRO2 in all brain areas to 56-70% and 50-68% of baseline, respectively (P < 0.05). The adjunct N2O counteracted some of the rCMRO2 and rCBF reductions caused by drugs alone, and especially during S+N, a widespread reduction (P < 0.05 for all cortex and cerebellum vs. awake) in the oxygen extraction fraction was seen. Adding of N2O did not alter the rCBV effects of sevoflurane and propofol alone. CONCLUSIONS: Propofol reduced rCBF and rCMRO2 comparably. Sevoflurane reduced rCBF less than propofol but rCMRO2 to an extent similar to propofol. These reductions in flow and metabolism were partly attenuated by adjunct N2O. S+N especially reduced the oxygen extraction fraction, suggesting disturbed flow-activity coupling in humans at a moderate depth of anesthesia.     

Response surface modeling of alfentanil-sevoflurane interaction on cardiorespiratory control and bispectral index

BACKGROUND: Respiratory depression is a serious side effect of anesthetics and opioids. The authors examined the influence of the combined administration of sevoflurane and alfentanil on ventilatory control, heart rate (HR), and Bispectral Index (BIS) in healthy volunteers. METHODS: Step decreases in end-tidal partial pressure of oxygen from normoxia into hypoxia (approximately 50 mmHg) at constant end-tidal partial pressure of carbon dioxide (approximately 48 mmHg) were performed in nine male volunteers at various concentrations of alfentanil and sevoflurane, ranging from 0 to 50 ng/ml for alfentanil and from 0 to 0.4 end-tidal concentration (ET%) for sevoflurane, and with various combinations of alfentanil and sevoflurane. The alfentanil-sevoflurane interactions on normoxic resting (hypercapnic) ventilation (Vi), HR, hypoxic Vi, and HR responses and BIS were assessed by construction of response surfaces that related alfentanil and sevoflurane to effect using a population analysis. RESULTS: Concentration-effect relations were linear for alfentanil and sevoflurane. Synergistic interactions were observed for resting Vi and resting HR. Depression of Vi by 25% occurred at 38 +/- 11 ng/ml alfentanil (population mean +/- SE) and at 0.7 +/- 0.4 ET% sevoflurane. One possibility for 25% reduction when alfentanil and sevoflurane are combined is 13.4 ng/ml alfentanil plus 0.12 ET% sevoflurane. Additive interactions were observed for hypoxic Vi and HR responses and BIS. Depression of the hypoxic Vi response by 25% occurred at 16 +/- 1 ng/ml alfentanil and 0.14 +/- 0.05 ET% sevoflurane. The effect of sevoflurane on the BIS (25% reduction of BIS occurred at 0.45 +/- 0.08 ET%) was independent of the alfentanil concentration. CONCLUSIONS: Response surface modeling was used successfully to analyze the effect of interactions between two drugs on respiration. The combination of alfentanil and sevoflurane causes more depression of Vi and HR than does the summed effect of each drug administered separately. The effects of combining alfentanil and sevoflurane on hypoxic Vi and HR responses and BIS could be predicted from the separate dose-response curves. Over the dose range tested, the hypoxic response is more sensitive to the effects of anesthetics and opioids relative to resting ventilation.     

The influence of intermittent hemodialysis (HD) on bispectral index (scale) (BIS) and serum propofol concentration under postoperative intravenous sedation

We experienced a case of postoperative intravenous sedation with propofol during intermittent hemodialysis (HD), and investigated the correlation between the clinical sedation level based on bispectral index scale (BIS) together with Ramsay score, and the serum concentration of propofol. One adult oral cancer patient (carcinoma of the lower gingiva) with end-stage renal dysfunction needing HD was selected for this study. The day after operation, HD was commenced under intravenous sedation with propofol. Clinical sedation level was assessed using BIS and Ramsay score, and serum propofol concentrations were determined in arterial blood samples. Serum concentrations were measured every 15 times until 51 hours after operation. The initial dose of propofol was set at 3.5 mg x kg(-1) x h(-1) on the basis of clinical symptoms. According to BIS and Ramsay score, sedation level decreased lineally for 1 hour after commencement of HD. In contrast, serum propofol concentration incresed from 1.71 microg x ml(-1) to 2.21 microg x ml(-1). Total serum concentration of propofol was enhanced during HD because of dialytic dehydration, but, according to BIS and Ramsay scores, the possibility was suggested that the fraction of albmin-unbound propofol with pharmacological activities was eliminated or absorbed by membrane during HD.     

Inhibitory Effects of the Anesthetics Propofol and Sevoflurane on Spontaneous Lymphatic Vessel Activity in Rats

Background: The effects of propofol and sevoflurane on lymphatic vessel activity are unknown. This study aimed to clarify the effects of these anesthetics on lymphatic vessel activity in rats by the use of a technique for mechanical removal of the endothelium.

Methods: The authors first examined the effects of propofol (8 mg/kg) and sevoflurane (2.0%) on in vivo lymphatic flow by injection of dye into the femoral regions of rats. In the in vitro study, the ends of the vessel segments of rat thoracic duct were connected to a syringe and stopcock, respectively. Spontaneous changes in diameter of each segment were monitored, and the extraluminal side of each segment was exposed to propofol (1 x 10-6 ~ 3 x 10-5 M) or sevoflurane (0.5~2.0%). Endothelial function was eliminated by perfusion of air into the lumen.

Results: In the dye uptake study, 80% of iliac lymphatic nodes were positively stained in a control group, whereas only 10% and 20% were positively stained in propofol and sevoflurane groups, respectively. In the in vitro study, both of the anesthetics significantly decreased the amplitude of spontaneous activity of lymphatic vessels with or without endothelial function. Sevoflurane inhibited the frequency of lymphatic vessel activity but propofol had no effect on it. When the endothelial function was eliminated, both anesthetics decreased the frequency of spontaneous activity of lymphatic vessels.