Cerebrospinal fluid creatine kinase-BB isoenzyme activity and outcome after subarachnoid hemorrhage.

BACKGROUND: The brain is rich in creatine kinase-BB isoenzyme activity (CK-BB), which is not normally present in cerebrospinal fluid (CSF). Results of previous studies have shown that CK-BB can be detected in the CSF of patients with aneurysmal subarachnoid hemorrhage (SAH), but whether CK-BB levels correlate with patients' neurologic outcomes is unknown. OBJECTIVE: To evaluate the relationship between CSF CK-BB level and outcome after SAH. DESIGN: Prospective observational cohort. SETTING: University-affiliated tertiary care center. PATIENTS: Convenience sample of 30 patients seen for cerebral aneurysm clipping. INTERVENTIONS: We sampled and assayed CSF for CK isoenzymes a median of 3 days after SAH in 27 patients, and at the time of unruptured aneurysm clipping in 3 patients. MAIN OUTCOME MEASURES: Without knowledge of CK results, we assigned the Glasgow Outcome Scale score early (approximately 1 week) and late (approximately 2 months) after surgery. RESULTS: Higher CSF CK-BB levels were associated with higher Hunt and Hess grades at hospital admission (Spearman rank correlation, p = 0.69; P<.001), lower Glasgow Coma Scale scores at hospital admission (p = -0.72; P<.001), and worse early outcomes on the Glasgow Outcome Scale (p = -0.64; P<.001). For patients with a favorable early outcome (Glasgow Outcome Scale score, 3-5), all CK-BB levels were less than 40 U/L. With a cutoff value of 40 U/L, CK-BB had a sensitivity of 70% and a specificity of 100% for predicting unfavorable early outcome (Glasgow Outcome Scale score, 1-2). Having a CK-BB level greater than 40 U/L increased the chance of an unfavorable early outcome, from 33% (previous probability) to 100%, whereas a CK-BB level of 40 U/L or less decreased it to 13%. Similar findings were obtained when considering late outcomes. CONCLUSION: The level of CSF CK-BB may help predict neurologic outcome after SAH.

The variability of cerebrovascular reactivity with posture and time.

Transcranial Doppler (TCD) ultrasonography has been used in a variety of clinical contexts to assess cerebrovascular reserve by measuring carbon dioxide reactivity. Reproducibility with time and altered position of the patient is examined in the present study. Carbon dioxide reactivity was determined in 10 healthy volunteers using TCD. Hypocarbia was produced by voluntary hyperventilation, and hypercarbia was produced by rebreathing from a circuit primed with 7% carbon dioxide. Each patient was studied in the supine position twice (1 week apart) and once in the seated position. Carbon dioxide reactivity was determined from linear regression analysis of paired middle cerebral artery flow velocity and end-tidal carbon dioxide values. Analysis of covariance for repeated measures was used for statistical analysis. Both the absolute slope and the relative slope (absolute slope expressed as a percentage of flow velocity at 40 mm Hg) were compared. In the supine position, flow velocity, absolute and relative slopes, and mean arterial pressure were similar from one week to the next at all carbon dioxide levels. In contrast, flow velocity, mean arterial pressure (adjusted for hydrostatic gradient), and absolute slope were decreased in the seated position (p < 0.05). No difference was observed when the relative slope was used for comparison. We conclude that absolute carbon dioxide reactivity is reproducible over time but may be influenced by position. Relative reactivity (relative slope), however, was both time and position independent.

Jugular bulb oximetry for the monitoring of cerebral blood flow and metabolism.

Jugular bulb oximetry can be used to assess the balance between oxygen supply and demand to the brain, measure metabolic byproducts, and determine cerebral blood flow. It has been useful in guiding the management of patients who are at risk of developing global ischemia. In this article, the principles upon which this monitor is based are discussed. Technical considerations such as placement techniques, factors affecting accuracy, limitations of the technique, and proper interpretation of oximetric values are reviewed. Lastly, specific clinical applications are presented.

Direct cerebrovasodilatory effects of halothane, isoflurane, and desflurane during propofol-induced isoelectric electroencephalogram in humans.

BACKGROUND: The effect of volatile anesthetics on cerebral blood flow depends on the balance between the agent's direct vasodilatory action and the indirect vasoconstrictive action mediated by flow-metabolism coupling. To compare the intrinsic action of volatile anesthetics, the effect of halothane, isoflurane, and desflurane on flow velocity in the middle cerebral artery during propofol-induced isoelectricity of the electroencephalogram was examined. METHODS: In 21 ASA physical status 1-2 patients, anesthesia was induced with 2.5 mg/kg propofol, 3 micrograms/kg fentanyl, and 0.1 mg/kg vecuronium and maintained with a propofol infusion to preserve an isoelectric electroencephalogram. End-tidal carbon dioxide and blood pressure were maintained constant throughout the study period. A transcranial Doppler was used to measure blood flow velocity in the middle cerebral artery, and a catheter was inserted in a retrograde direction into the jugular bulb for oxygen saturation measurements. After 15 min of isoelectric electroencephalogram, arterial and jugular venous blood samples were drawn, and flow velocity in the middle cerebral artery was recorded. Patients were randomly allocated to receive 0.5 MAC halothane, isoflurane, or desflurane, and after 15 min of equilibration, all variables were measured again. The concentration of the volatile agent was increased to 1.5 MAC, and after 15 min of equilibration, the measurements were repeated. RESULTS: Halothane, isoflurane, and desflurane significantly increased flow velocity in the middle cerebral artery (baseline 28 +/- 4, 30 +/- 4, and 29 +/- 3 cm/s, respectively) at 0.5 MAC (19 +/- 1.5%, 21 +/- 2%, and 23 +/- 3%, respectively; P < 0.05) and at 1.5 MAC (48 +/- 3%, 75 +/- 7%, and 74 +/- 4%, respectively; P < 0.05). Changes in the cerebral arteriovenous oxygen content difference are consistent with these findings. CONCLUSIONS: Halothane, isoflurane, and desflurane have intrinsic, dose-related cerebral vasodilatory effects. Whereas all three agents are similar at 0.5 MAC, isoflurane and desflurane have greater vasodilatory effects than halothane at 1.5 MAC.

Accuracy of continuous jugular bulb venous oximetry during intracranial surgery.

We compared readings obtained from the Baxter-Edwards continuous jugular bulb venous oximetry catheter with those obtained from blood gas analysis of simultaneously drawn samples from the catheter in 12 patients undergoing neurosurgical procedures. Within the range studied (SjvO2, 42-95%), the 111 (median, nine samples per patient; range five to 17) oximetric catheter readings correlated well with hemoglobin oxygen saturation values obtained from in vitro analysis of simultaneously drawn blood samples from the catheter (y = 0.93x + 3.4, r = 0.94, p < 0.001). Fiberoptic light signal was suboptimal (signal quality index = 3 or 4) on fewer than five occasions per patient during an average surgical procedure duration of seven h, and these occurrences were generally corrected by flushing the catheter. We conclude that the Baxter-Edwards jugular bulb oximetric catheter provides an accurate measure of SjvO2 during neurosurgical procedures.

Change in cerebral blood flow velocity with onset of EEG silence during inhalation anesthesia in humans: evidence of flow-metabolism coupling?

In eight subjects anesthetized with moderate to high doses of inhalation anesthetics (isoflurane or desflurane) during normocapnia, the onset of electrical silence in EEG was associated with a sudden reduction of blood flow velocity monitored from the middle cerebral artery. The magnitude of this reduction was 38 +/- 11% (mean +/- SD; range 24-44%). The change in EEG always preceded the change in flow velocity by 5-7 s. These observations suggest that some flow-metabolism coupling mechanism is preserved during inhalation anesthesia in humans.

Dynamic and static cerebral autoregulation during isoflurane, desflurane, and propofol anesthesia.

BACKGROUND: Although inhalation anesthetic agents are thought to impair cerebral autoregulation more than intravenous agents, there are few controlled studies in humans. METHODS: In the first group (n = 24), dynamic autoregulation was assessed from the response of middle cerebral artery blood flow velocity (Vmca) to a transient step decrease in mean arterial blood pressure (MABP). The transient hypotension was induced by rapid deflation of thigh cuffs after inflation for 3 min. In the second group (n = 18), static autoregulation was studied by observing Vmca in response to a phenylephrine-induced increase in MABP. All patients were studied during fentanyl (3 micrograms.kg-1.h-1)/nitrous oxide (70%) anesthesia, followed by, in a randomized manner, isoflurane, desflurane, or propofol in a low dose (0.5 MAC or 100 micrograms.kg-1.min-1) and a high dose (1.5 MAC or 200 micrograms.kg-1.min-1). The dynamic rate of regulation (dROR) was assessed from the rate of change in cerebrovascular resistance (MABP/Vmca) with the blood pressure decreases using computer modeling, whereas the static rate of regulation (sROR) was assessed from the change in Vmca with the change in MABP. RESULTS: Low-dose isoflurane delayed (dROR decreased) but did not reduce the autoregulatory response (sROR intact). Low-dose desflurane decreased both dROR and sROR. During 1.5 MAC isoflurane or desflurane, autoregulation was ablated (both dROR and sROR impaired). Neither dROR nor sROR changed with low- or high-dose propofol. CONCLUSIONS: At 1.5 MAC, isoflurane and desflurane impaired autoregulation whereas propofol (200 micrograms.kg-1.min-1) preserved it.

Ketamine does not increase cerebral blood flow velocity or intracranial pressure during isoflurane/nitrous oxide anesthesia in patients undergoing craniotomy.

Ketamine's effect on cerebral hemodynamics is controversial. We hypothesized that ketamine would not increase intracranial pressure (ICP) and cerebral blood flow (CBF) velocity in anesthetized, ventilated patients. Twenty patients requiring craniotomy for brain tumor or cerebral aneurysm were studied. After induction with thiopental, anesthesia was maintained with isoflurane and nitrous oxide in oxygen. During controlled ventilation (PaCO2 34 +/- 1 mm Hg); middle cerebral artery blood flow velocity (VMCA), mean arterial blood pressure (MAP), bilateral frontooccipital processed electroencephalogram (EEG), and ICP were measured before and for 10 min after intravenous ketamine 1.0 mg/kg. Cerebral arteriovenous oxygen content difference (AVDO2) and cerebral perfusion pressure (CPP) were calculated. After ketamine, MAP, CPP, PaCO2, and AVDO2 were unchanged. ICP decreased from 16 +/- 1 mm Hg to 14 +/- 1 mm Hg (mean +/- SE; P < 0.001) and VMCA decreased from 44 +/- 4 cm/s to 39 +/- 4 cm/s (P < 0.001). Total EEG power decreased (P < 0.02). These results suggest that ketamine can be used in anesthetized, mechanically ventilated patients with mildly increased ICP without adversely altering cerebral hemodynamics.

Cerebrovascular response to carbon dioxide during sodium nitroprusside- and isoflurane-induced hypotension.

We have examined the cerebrovascular response to carbon dioxide during normotension, sodium nitroprusside (SNP)-induced hypotension and high dose isoflurane-induced hypotension in 10 patients who received a standardized general anaesthetic. Carbon dioxide reactivity was determined by varying PaCO2 between 3.0 and 8.0 kPa and recording simultaneously blood flow velocity from the middle cerebral artery (vmca). The paired vmca-PaCO2 data were analysed using linear regression to determine carbon dioxide reactivity. During hypotension, both high-dose isoflurane and SNP reduced significantly mean absolute (from 17.4 (SEM 2.3) to 13.0 (1.7) and 8.8 (1.3) cm s-1 kPa-1, respectively; P < 0.05) and relative (from 32.5 (3.8) to 23.6 (2.0) and 15.5 (1.3)% kPa-1, respectively; P < 0.05) cerebrovascular reactivity to carbon dioxide. This reduction was greater during SNP-induced hypotension (P < 0.05). We conclude that cerebrovascular reactivity to carbon dioxide was attenuated during isoflurane and SNP-induced hypotension, and that it was better preserved during isoflurane-induced hypotension.

Cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced EEG suppression.

We studied cerebral pressure autoregulation and carbon dioxide reactivity during propofol-induced electrical silence of the electroencephalogram (EEG) in 10 patients. Anaesthesia was induced with propofol 2.5 mg kg-1, fentanyl 3 micrograms kg-1 and vecuronium 0.1 mg kg-1, and a propofol infusion of 250-300 micrograms kg-1 min-1 was used to induce EEG silence. Cerebral pressure autoregulation was tested by increasing mean arterial pressure (MAP) by 24 (SEM 5) mm Hg from baseline with an infusion of phenylephrine and simultaneously recording middle cerebral artery blood flow velocity (vmca) using transcranial Doppler. Carbon dioxide reactivity was tested by varying PaCO2 between 4.0 and 7.0 kPa and recording vmca simultaneously. Although absolute carbon dioxide reactivity was reduced, relative carbon dioxide reactivity was within normal limits for all patients studied (mean 8.5 (SEM 0.8) cm s-1 kPa-1 and 22 (2)% kPa-1, respectively). No significant change in vmca (34 (2) and 35 (2) cm s-1) was observed with the increase in MAP (77 (4) to 101 (4) mm Hg) during autoregulation testing. We conclude that cerebral carbon dioxide reactivity and pressure autoregulation remain intact during propofol-induced isoelectric EEG.

The influence of arterial oxygenation on cerebral venous oxygen saturation during hyperventilation.

Cerebral venous oxygen desaturation may occur when hyperventilation is employed during neurosurgical procedures. In this study, we examined the effect of arterial hyperoxia (PaO2 > 200 mmHg) on jugular bulb venous oxygen tension (PjvO2), saturation (SjvO2) and content (CjvO2) in 12 patients undergoing anaesthesia for neurosurgical procedures. Under stable anaesthetic conditions, the inspired oxygen fraction (FIO2) was varied to give four different levels of arterial oxygen tension (PaO2 100-200, 201-300, 301-400, and > 400 mmHg), at two levels of controlled hyperventilation (PaCO2(25) and 30 mmHg). In five patients, a transcranial Doppler probe was used to insonate the middle cerebral artery throughout the study period. Regression lines were constructed for each patient for the PjvO2, SjvO2 and the corresponding PaO2 for both levels of PaCO2 (all PjvO2-PaO2 and SjvO2-PaO2 regression lines r2 > 0.85, P < 0.0001). From these lines we calculated the PjvO2, SjvO2 and CjvO2 at PaO2 of 100, 250 and 400 mmHg, at each level of PaCO2 for each patient. At PaCO2 of 25 mmHg, hyperoxaemia increased PjvO2 (from 27.6 +/- 1.1 mmHg at PaO2 of 100 mmHg to 30.6 +/- 1.4 and 33.6 +/- 1.8 mmHg at PaO2 of 250 and 400 mmHg respectively) and SjvO2 (from 54 +/- 3% at PaO2 of 100 mmHg to 60 +/- 3 and 65 +/- 3% at PaO2 of 250 and 400 mmHg respectively, P < 0.05). Hyperoxaemia had a similar effect on SjvO2 and PjvO2 at a PaCO2 of 30 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

A critique of the intraoperative use of jugular venous bulb catheters during neurosurgical procedures.

We examined the intraoperative use of jugular venous bulb catheters in 100 consecutive patients undergoing neurosurgical procedures. The catheters were successfully placed after induction of anesthesia in 99 patients using an aseptic technique. The efforts were abandoned after four attempts in the remaining patient. The mean time of insertion was 94 s (SD 108, range 15-420). Carotid artery puncture on two occasions controlled by firm pressure was the only complication. Arterial blood pressure, PaCO2, PaO2, and jugular venous bulb oxygen saturations (SjVO2) were intermittently measured at set intervals throughout the operation. We defined cerebral venous desaturation as 1) none (SjVO2 > 50%), 2) mild (45% < SjVO2 < 50%), and 3) severe (SjVO2 < 45%). We graded the usefulness of the catheter as 1) not useful (NU), SjVO2 > 50% and PaCO2 > 25 mm Hg; 2) useful (U1), SjVO2 > 50% and PaCO2 < 25 mm Hg; intervention, no increase in PaCO2; 3) useful (U2), SjVO2 < 50% and PaCO2 < 25 mm Hg; intervention, increase PaCO2 to improve SjVO2; 4) useful (U3), SjVO2 < 50% and PaCO2 > 25 mm Hg; intervention, nonventilatory action to increase SjVO2 (e.g., infusion of mannitol). Mild desaturation was detected in 24 patients and severe desaturation was present in 17 patients. We found SjVO2 monitoring to be useful in 60 of 99 patients studied. It was useful for detecting and treating cerebral venous desaturation in 13 of 18 patients with intracranial hematomas (subdural, epidural, and intracerebral hematomas), 9 of 18 patients with intracerebral tumors, 27 of 45 patients with cerebral aneurysms, and 6 of 8 patients with other intracranial pathology.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of flow and velocity during dynamic autoregulation testing in humans.

BACKGROUND AND PURPOSE: We compared relative changes in middle cerebral artery velocity and internal carotid artery flow during autoregulation testing to test the validity of using transcranial Doppler recordings of middle cerebral artery velocity to evaluate cerebral autoregulation in humans. METHODS: Seven human volunteers had dynamic autoregulation tested during surgical procedures that included exposure of the internal carotid artery. The mean arterial blood pressure and middle cerebral artery velocity spectral outline (Vmax), using transcranial Doppler, and ipsilateral internal carotid artery flow, using an electromagnetic flowmeter, were continuously and simultaneously recorded during transient sharp decreases in blood pressure that were induced by rapid deflation of thigh blood pressure cuffs. The resulting responses of velocity in the middle cerebral artery and flow in the internal carotid artery were compared. RESULTS: Moderate decreases in blood pressure evoked responses in cerebral autoregulation. There were no significant (P = .97) differences between the responses in middle cerebral artery velocity and internal carotid artery flow to the blood pressure decreases. CONCLUSIONS: Relative changes in Vmax accurately reflect relative changes in internal carotid artery flow during dynamic autoregulation testing in humans. Therefore, alterations in middle cerebral artery diameter do not occur to the extent that they introduce a significant error in making these comparisons.

Isoflurane compared with nitrous oxide anaesthesia for intraoperative monitoring of somatosensory-evoked potentials.

Intraoperative monitoring of somatosensory-evoked potentials is a routine procedure. To determine the depressant effect of nitrous oxide relative to isoflurane, the authors recorded the scalp, cervical and brachial plexus-evoked responses to stimulation of the median nerve under different anaesthetic conditions. Eight subjects, age 35 +/- 6 (SD) yr, weight 68 +/- 12 kg, were studied. Following recording of awake control responses, anaesthesia was induced with thiopentone 5 mg.kg-1 and fentanyl 3 micrograms.kg-1 and was followed by succinylcholine 1 mg.kg-1. During normocapnia and normothermia, and with a maintenance infusion of fentanyl 3 micrograms.kg-1.hr-1, evoked potential recording was repeated under three different anaesthetic conditions; 0.6 MAC nitrous oxide, 0.6 MAC nitrous oxide +/- 0.6 MAC isoflurane, and 0.6 MAC isoflurane. Among the anesthetic conditions, the combination of nitrous oxide-isoflurane had the most depressant effect on the cortical amplitude (67 +/- 4% reduction, P < 0.05). Nitrous oxide decreased the cortical amplitude more than an equipotent dose of isoflurane (60 +/- 4% vs 48 +/- 7%, P < 0.05). The latency was unchanged by nitrous oxide, but increased slightly by isoflurane and isoflurane-nitrous oxide anaesthesia (1.0 and 0.9 msec respectively, P < 0.05). We conclude that somatosensory-evoked potential monitoring is feasible both during nitrous oxide anaesthesia and isoflurane anaesthesia, but the cortical amplitude is better preserved during 0.6 MAC of isoflurane alone relative to 0.6 MAC of nitrous oxide alone. The depressant effect is maximal during nitrous oxide-isoflurane anaesthesia but less than the predicted additive effect.

Succinylcholine does not change intracranial pressure, cerebral blood flow velocity, or the electroencephalogram in patients with neurologic injury.

The effect of succinylcholine (SCh) on intracranial pressure (ICP) was studied in 10 mechanically ventilated patients (Glasgow coma scale score 3-10, median 6) being treated for increased ICP in an intensive care unit. Mean arterial blood pressure (MAP), ICP, processed electroencephalogram (EEG), and mean middle cerebral artery blood flow velocity (V mca) were monitored. Baseline measurements after saline injection were obtained for 5 min. SCh (1 mg/kg) was administered intravenously and the above variables were monitored for 15 min. Neither saline nor SCh cause any significant change in cerebral perfusion pressure, MAP, V mca, EEG, or ICP. We conclude that in brain-injured patients, SCh did not alter cerebral blood flow velocity, cortical electrical activity, or ICP.

Nitrous oxide-isoflurane anesthesia causes more cerebral vasodilation than an equipotent dose of isoflurane in humans.

To compare the cerebral vascular and metabolic effect of an isoflurane-nitrous oxide mixture to an equipotent dose of isoflurane at 1.1 minimum alveolar anesthetic concentration (MAC), and to study the interaction between nitrous oxide and isoflurane anesthesia, we measured right middle cerebral artery blood flow velocity (V mca) and cerebral arteriovenous oxygen content difference (AVDO2) in six healthy patients during normocapnia and normothermia under the following sequence of steady-state anesthetic conditions: Condition A, 0.5 MAC of isoflurane, Condition B, 0.5 MAC of isoflurane + 0.6 MAC of N2O, Condition C, 1.1 MAC of isoflurane + 0.6 MAC of N2O, and Condition D, 1.1 MAC of isoflurane. The study entry sequence was randomized. V mca and AVDO2 during 1.1 MAC of isoflurane (Condition D) was 48 +/- 7 cm/s and 3.9 +/- 0.6 vol%, respectively. Substituting 0.6 MAC of isoflurane with an equipotent concentration of N2O (Condition B) resulted in an increase in both V mca and AVDO2 of approximately 20% (P < 0.05). These findings suggest that the increase in flow was accompanied by an even greater increase in metabolic rate. Adding 0.6 MAC of N2O to 1.1 MAC of isoflurane (Condition C) also increased V mca (P < 0.05). We conclude that N2O is a more potent cerebral vasodilator than an equipotent dose of isoflurane alone in humans.

The effect of alfentanil on cerebral blood flow velocity and intracranial pressure during isoflurane-nitrous oxide anesthesia in humans.

BACKGROUND: Intravenous opioids often are used as a component of anesthesia during neurosurgical procedures. However, the cerebrovascular effects of alfentanil administered to patients are controversial. In this study, the effect of alfentanil in patients with and without intracranial pathology was studied. METHODS: Sixteen neurosurgical patients and 16 patients scheduled for orthopedic procedures were studied. Anesthesia was maintained with isoflurane (0.4-0.6 vol% inspired) and nitrous oxide (50%) in oxygen. Within each group, the patients were assigned randomly to receive either 25 or 50 micrograms/kg intravenous alfentanil. During normocapnia and without surgical stimulation, the right middle cerebral artery flow velocity, and mean arterial pressure were measured every minute for 10 min after the administration of alfentanil. In the neurosurgical patients, intracranial pressure, cerebral perfusion pressure, and cerebral arteriovenous oxygen content difference were determined also. Neurosurgical patients received intravenous phenylephrine to maintain mean arterial pressure as needed. RESULTS: There was no significant change in middle cerebral artery flow velocity and arteriovenous oxygen content difference in the neurosurgical patients. In the high-dose group, intracranial pressure increased by 2 mmHg at 4 min but was otherwise unchanged. Despite phenylephrine administration, there was an immediate but transient decrease in mean arterial pressure in the high-dose group and a corresponding decrease in cerebral perfusion pressure. In the orthopedic patients, mean arterial pressure decreased significantly. Middle cerebral artery flow velocity decreased in the high-dose group but remained unchanged in the low-dose group. CONCLUSIONS: Based on the flow velocity and metabolic data, alfentanil is neither a cerebral vasodilator nor a vasoconstrictor in these doses. Furthermore, there was no clinically significant increase in intracranial pressure when alfentanil was administered in either dose.

The influence of propofol with and without nitrous oxide on cerebral blood flow velocity and CO2 reactivity in humans.

The cerebrovascular response to CO2 has been reported to be preserved during propofol anesthesia, but no comparison with awake control values has been made, and the additional influence of N2O has not been investigated. Using the noninvasive technique of transcranial Doppler ultrasonography, this study investigated the cerebrovascular response to varying levels of PaCO2 while awake and during anesthesia with propofol and propofol/N2O. Seven adults without systemic diseases undergoing nonneurologic surgery were studied. A pulsed-wave Doppler monitor was used to measure the mean middle cerebral artery flow velocity (Vmca) during varying levels of PaCO2 (25-55 mmHg) under the following conditions: 1) awake; 2) propofol 2.5 mg.kg-1 bolus followed by continuous infusion of 150 micrograms.kg-1.min-1; and 3) propofol as in the condition above plus 70% N2O. During the awake study condition, hypocapnia was induced by voluntary hyperventilation, and hypercapnia was induced with rebreathing of 7% CO2 in a closed circuit. During the anesthetized study conditions, hypocapnia and hypercapnia were induced by adjustment of minute ventilation. A minimum of five to six simultaneous Vmca and PaCO2 measurements were obtained under each of the study conditions. Systemic blood pressure was monitored via a radial arterial catheter, and phenylephrine was administered if mean arterial blood pressure decreased below 60 mmHg (phenylephrine was used in three of five patients in the propofol-N2O group). Linear regression and analysis of covariance were used for statistical analysis of Vmca-PaCO2 relationships.(ABSTRACT TRUNCATED AT 250 WORDS)