The effect of sevoflurane on cerebral autoregulation in young children as assessed by the transient hyperemic response

The transient hyperemic response (THR) test is a simple, noninvasive technique to evaluate cerebral autoregulation using transcranial Doppler. It has not yet been used in studies involving children. In this study we evaluated this response in children undergoing general anesthesia using sevoflurane. Twenty ASA physical status I children undergoing elective urological surgery sequentially received sevoflurane at 0.5, 1.0, and 1.5 MAC in a randomized order. Analgesia was solely provided by caudal anesthesia. The right middle cerebral artery flow velocities before (F1), during (F2), and after (F3) a 10-s ipsilateral carotid artery compression were recorded. The THR ratios (THRR) (+/- sd) for 0.5 MAC, 1.0 MAC, and 1.5 MAC were 1.24 +/- 0.11, 1.16 +/- 0.09, and 1.13 +/- 0.07, respectively. The THRR was significantly different between 0.5 MAC versus 1.0 and 1.5 MAC, respectively (P < 0.05). However, no difference was detected between 1.0 and 1.5 MAC. A THRR of more than 1.09 has previously been accepted as the lower limit of a positive response. The results in this study suggest that THR is affected by sevoflurane in a dose-dependent fashion but is maintained at up to 1.5 MAC. This suggests cerebral autoregulation is preserved in children anesthetized with up to 1.5 MAC sevoflurane.     

Blood Flow Velocity of Middle Cerebral Artery during Prolonged Anesthesia with Halothane, Isoflurane, and Sevoflurane in Humans

Background: It is not clear whether the increase of cerebral blood flow (CBF) produced by volatile anesthetics is maintained during prolonged anesthesia. In a previous study, the authors found that CBF equivalent, an index of flow-metabolism relationship, was stable over 3 h, suggesting no decay over time in CBF for 3 h during volatile anesthesia in humans. However, it may be possible that CBF changes in a parallel fashion to functional metabolic changes. In this study, to estimate the response of CBF to three volatile anesthetics, the authors used transcranial Doppler (TCD) ultrasonography to measure time-averaged mean velocity in the middle cerebral artery (Vmca).

Methods: Twenty-four surgical patients were randomly assigned to three groups to receive halothane, isoflurane, or sevoflurane (eight patients, each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5, 1.0, and 1.5 MAC before surgery and then at 1.5 MAC during surgery, which lasted more than 3 h. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 70 mmHg, using phenylephrine infusion, if necessary. TCD recordings of the Vmca were performed continuously.

Results: Vmca at 0.5 MAC of halothane, isoflurane, and sevoflurane was 49 +/- 19, 57 +/- 8, and 48 +/- 13 cm/s, respectively. Halothane significantly (P < 0.01) increased Vmca in a dose-dependent manner (0.5, 1.0, 1.5 MAC), whereas isoflurane and sevoflurane produced no significant dose-related changes. At 1.5 MAC for 3 h, Vmca changed significantly (P < 0.05) for the time trends, but it did not exhibit decay over time with all drugs. During burst suppression, observed electroencephalographically (EEG) on patients during isoflurane and sevoflurane anesthesia, the onset of a burst increased Vmca (approximately 5-30 cm/s), which was maintained for the duration of the burst.     

The comparative effects of sevoflurane versus isoflurane on cerebrovascular carbon dioxide reactivity in patients with previous stroke

PURPOSE: The use of volatile anesthetics is reportedly related to altered cerebrovascular carbon dioxide (CO2) reactivity. We examined the comparative effects of sevoflurane versus isoflurane on cerebrovascular CO2 reactivity in patients with previous stroke. METHODS: Twenty-four patients with previous stroke and 20 patients without previous stroke (serving as controls) were studied. Anesthesia was maintained with either end-tidal 1.0 minimum alveolar concentration (MAC) sevoflurane or 1.0 MAC isoflurane in 33% oxygen and 67% nitrous oxide. A 2.5-MHz pulsed transcranial Doppler (TCD) probe was attached to the patient's head at the right or left temporal window for continuous measurement of mean blood flow velocity in the middle cerebral artery (Vmca). After establishing baseline values of Vmca and cardiovascular hemodynamics, we increased end-tidal CO2 by decreasing the ventilatory frequency by 2-5 breaths x min(-1). RESULTS: We found that values for absolute and relative CO2 reactivity in the sevoflurane groups were lower than those in the isoflurane groups (absolute CO2 reactivity in the sevoflurane groups: control, 3.3 +/- 0.4*; previous stroke, 3.4 +/- 0.4*; absolute CO2 reactivity in the isoflurane groups: control, 4.2 +/- 0.3; previous stroke, 4.5 +/- 0.4, cm x s(-1) x mmHg(-1); *P < 0.05 compared with isoflurane group). There were no significant differences in the values for absolute and relative CO2 reactivity between the controls and the previous-stroke patients within each of the sevoflurane and isoflurane groups. CONCLUSION: Our findings suggest that, in patients with previous stroke, cerebrovascular CO2 reactivity under sevoflurane anesthesia was lower than that under isoflurane anesthesia.     

Effects of Sevoflurane with and without Nitrous Oxide on Human Cerebral Circulation: Transcranial Doppler Study

Background: This study was designed to evaluate the effects of sevoflurane with and without nitrous oxide on human middle cerebral artery (MCA) flow velocity, cerebrovascular carbon dioxide reactivity, and autoregulation compared with the awake state using transcranial Doppler ultrasonography.

Methods: In 14 patients, the time-mean middle cerebral artery flow velocity (Vmca) was measured when the end-tidal carbon dioxide level was approximately 30, 40, and 50 mmHg under the following conditions: (1) awake; (2) with 2% (1.2 MAC) sevoflurane; and (3) with 1.2 MAC sevoflurane-60% nitrous oxide. In six other patients, the cerebrovascular autoregulation during anesthesia was determined using intravenous phenylephrine to increase blood pressure.

Results: Sevoflurane (1.2 MAC) significantly decreased Vmca compared with the awake value at each level of end-tidal carbon dioxide, whereas 1.2 MAC sevoflurane-60% nitrous oxide did not exert significant influence. The Vmca in normocapnic patients decreased from 69 cm/s to 55 cm/s with 1.2 MAC sevoflurane and then increased to 70 cm/s when nitrous oxide was added. Sevoflurane (1.2 MAC) with and without 60% nitrous oxide had a negligible effect on cerebrovascular carbon dioxide reactivity. A phenylephrine-induced increase of mean arterial pressure did not influence Vmca during anesthesia.     

The effect of sevoflurane on cerebral blood flow velocity in children

BACKGROUND: Sevoflurane is a suitable agent for neuroanesthesia in adult patients. In children, cerebrovascular carbon dioxide reactivity is maintained during hypo- and normocapnia under sevoflurane anesthesia. To determine the effects of sevoflurane on middle cerebral artery blood flow velocity (Vmca) in neurologically normal children, Vmca was measured both at different MAC values and at one MAC over a specified time period, using transcranial Doppler sonography. METHODS: Twenty-six healthy children undergoing elective urological surgery were enrolled (16 patients in part I and 10 in part II). In part I of the study anesthesia comprised sevoflurane 0.5, 1.0 and 1.5 MAC in 30% oxygen and a caudal epidural block. Once steady state had been reached at each sevoflurane MAC level, three measurements of Vmca, mean arterial pressure (MAP) and heart rate (HR) were recorded. In part II of the study patients received sevoflurane 1.0 MAC over a 90-min period, with the same variables being recorded at 15-min intervals. RESULTS: Vmca did not vary significantly at 0.5, 1.0 and 1.5 MAC sevoflurane. There was a significant decrease in MAP between 0.5 MAC and 1.0 MAC sevoflurane (P < 0.005) and also between 1.0 MAC and 1.5 MAC (P < 0.01). There was no significant change in Vmca over 90 min at 1.0 MAC sevoflurane. CONCLUSION: Sevoflurane does not significantly affect cerebral blood flow velocity in healthy children at working concentrations.     

A comparison of the transient hyperemic response test and the static autoregulation test to assess graded impairment in cerebral autoregulation during propofol, desflurane, and nitrous oxide anesthesia.

The transient hyperemic response (THR) test has been used to assess cerebral autoregulation in anesthesia and intensive care. To date it has not been compared with the static autoregulation test for assessing graded changes in cerebral autoregulation. We compared the two tests during propofol, desflurane, and nitrous oxide anesthesia. Seven subjects were studied. For the THR test, changes in the middle artery blood flow velocity were assessed during and after a 10-s compression of the ipsilateral common carotid artery. Two indices of autoregulation--THR ratio (THRR) and strength of autoregulation (SA)--were calculated. For the test of static autoregulation, changes in the middle cerebral artery flow velocity after a phenylephrine-induces increase in mean arterial pressure were assessed, and the static rate of regulation (sROR) was calculated. The tests were performed before induction and after equilibrium at 0.5 minimum alveolar anesthetic concentration (MAC) and then at 1.5 MAC of desflurane. THRR, SA and sROR decreased significantly (P < 0.001) at 0.5 MAC and then at 1.5 MAC desflurane. CHanges in THRR and SA reflected the changes in sROR with a sensitivity of 100%. Implications: When compared with the established test of static autoregulation, the transient hyperemic response test provides a valid method for assessing graded impairment in cerebral autoregulation.     

不同麻醉方法对神经外科手术患者脑血管自身调节功能影响的比较

目的 比较不同麻醉方法对神经外科手术患者脑血管自身调节功能的影响.方法 拟行颅脑肿瘤切除术患者69例,ASA分级Ⅱ或Ⅲ级,年龄23～62岁,采用随机数字表法,将患者随机分为3组(n=23):异丙酚-瑞芬太尼复合麻醉组(PR组)、七氟醚.瑞芬太尼复合麻醉组(SR组)和异丙酚-七氟醚-瑞芬太尼复合麻醉组(PSR组).麻醉诱导:PR组和PSR组TCI异丙酚,血浆靶浓度为3μg/ml;SR组吸入8%七氟醚;3组均静脉注射瑞芬太尼1 mg/kg和阿曲库铵0.5 mg/kg.气管插管后机械通气,维持PETCO2 32～35 mm Hg.麻醉维持:PR组TCI异丙酚,血浆靶浓度2.0～3.5/μg/ml,SR组吸入1.5%～2.5%七氟醚,PSR组TCI异丙酚(血浆靶浓度1.5～3.0 μg/ml)复合吸入1%七氟醚,3组均TCI瑞芬太尼(血浆靶浓度2.0～4.5 ng/ml),静脉输注阿曲库铵6 μg·kg-1·min-1,维持听觉诱发电位指数值40～45.分别于麻醉诱导前(基础状态,T0)、气管插管后即刻(T1)、打开颅骨前即刻(T2)及开始缝皮时(T3)记录大脑中动脉时间-平均峰值流速,于相应时点压迫一侧颈总动脉7 s,计算脑短暂充血反应率(THRR),以反映脑血管自身调节功能.结果 与T0时比较,PR组T2时THRR升高,SR组T2,3时THRR降低(P<0.05),PSR组THRR差异无统计学意义(P>0.05).与PR组比较,SR组和PSR组THRR降低(P<0.05);与SR组比较,PSR组THRR升高(P<0.05).结论 异丙酚-瑞芬太尼复合麻醉可提高神经外科手术患者脑血管自身调节功能,七氟醚-瑞芬太尼复合麻醉可降低其脑血管自身调节功能,异丙酚-七氟醚-瑞芬太尼复合麻醉对其脑血管自身调节功能无影响.

Abstract：

Objective To compare the effect of different methods of anesthesia on cerebral autoregulation in patients undergoing neurosurgery.Methods Sixty-nine ASA Ⅱ orⅢ patients with brain tumor, aged 23-62 yr, scheduled for neurosurgery under general anesthesia, were randomly divided into 3 groups ( n = 23 each) : propofol-remifentanil group (group PR), sevoflurane-remifentanil group (group SR) and propofol-sevoflurane-remifentanil group (group PSR) . Anesthesia was induced with target-controlled infusion (TCI) of propofol (target plasma concentration3 μg/ml, PR and PSR groups) or inhalation of 8% sevoflurane (group SR) and iv injection of remifentanil 1 mg/kg and atracurium 0.5 mg/kg. The patients were mechanically ventilated after tracheal intubation. PETCO2 was maintained at 32-35 mm Hg. Anesthesia was maintained with TCI of propofol (target plasma concentration 2.0-3.5 μg/ml) in group PR, with inhalation of 1.5%-2.5% sevoflurane in group SR, with TCI of propofol (target plasma concentration 1.5-3.0 μg/ml) and inhalation of 1% sevoflurane in group PSR, and with TCI of remifentanil (target plasma concentration 2.0-4.5 ng/ml) and iv infusion of atracurium at 6 μg · kg-1 · min-1 in all groups. Auditory evoked potential index was maintained between 40-45. The middle cerebral artery time-average peak flow velocity was recorded before induction (baseline) , immediately after intubation, immediately before craniotomy and at the beginning of skin suture. The unilateral carotid artery was compressed for 7 s at the corresponding time points mentioned above. The transient hyperemic response ratio (THRR) was calculated to reflect cerebral autoregulation. Results Compared with the baseline value at T0, THRR was significantly increased at T2in group PR and decreased at T2,3 in group SR (P <0.05) ,while no significant change was found in THRR at T1-3in group PSR (P >0.05). The THRR was significantly lower in SR and PSR groups than in group PR, and higher in group PSR than in group SR ( P < 0.05). Conclusion Propofol-remifentanil anesthesia can improve cerebral autoregulation, sevoflurane-remifentanil anesthesia can reduce cerebral autoregulation, and propofol-sevofluraneremifentanil anesthesia exerts no effect on cerebral autoregulation in patients undergoing neurosurgery.     

Cerebral autoregulation and CO2 reactivity in anterior and posterior cerebral circulation during sevoflurane anesthesia

The purpose of the study was to compare cerebral autoregulation (CA) and CO2 reactivity (CO2R) between the anterior and posterior circulation under sevoflurane anesthesia. We studied 9 adult ASA physical status I patients (22-47 yr) scheduled for elective orthopedic surgery. Blood flow velocity in the middle cerebral artery (Vmca) and in the basilar artery (Vba) were measured using transcranial Doppler ultrasonography. For CA testing, arterial blood pressure was increased using phenylephrine infusion. CA was quantified with the autoregulatory index (ARI). CO2R was investigated at PaCO2 of 30 +/- 2.8 mm Hg, 39.4 +/- 2.6 mm Hg, and 48.7 +/- 2.8 mm Hg. Linear regression analysis was used for CO2R. We found ARI was preserved in both arteries: ARImca (middle cerebral artery) = 0.72 +/- 0.2; ARIba (basilar artery) = 0.66 +/- 0.2; P = 0.5. With regard to CO2R, Vmca increased with slope of 1.7 cm/s/mm Hg PaCO2, Vba increased with slope of 1.5 cm/s/mm Hg PaCO2; P = 0.83. Absolute Vmca was higher compared with Vba; P < 0.05. We conclude that in healthy individuals under 0.5 MAC of sevoflurane and small-dose remifentanil: 1) mean flow velocities of BA are less than those of MCA; 2) autoregulation and CO2R are preserved in the basilar artery and are similar to those of MCA.     

Direct cerebral vasodilatory effects of sevoflurane and isoflurane.

BACKGROUND: The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram. METHODS: Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 micro/g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels. RESULTS: Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4+/-3 and 17+/-3% at 0.5 and 1.5 MAC sevoflurane; 19+/-3 and 72+/-9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P<0.05). All patients required phenylephrine (100-300 microg) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia. CONCLUSIONS: In common with other volatile anesthetic agents, sevoflurane has an intrinsic dose-dependent cerebral vasodilatory effect. However, this effect is less than that of isoflurane.     

The influence of nicardipine-, nitroglycerin-, and prostaglandin E(1)-induced hypotension on cerebral pressure autoregulation in adult patients during propofol-fentanyl anesthesia.

We investigated the influence of drug-induced hypotension at a mean arterial pressure (MAP) of 60-70 mm Hg on cerebral pressure autoregulation in 45 adult patients during propofol-fentanyl anesthesia. Time-averaged mean blood flow velocity in the right middle cerebral artery (Vmca) was continuously measured at a PaCO(2) of 39-40 mm Hg by using transcranial Doppler ultrasonography. Hypotension was induced and maintained with a continuous infusion of nicardipine, nitroglycerin, or prostaglandin E(1). Cerebral autoregulation was tested by a slow continuous infusion of phenylephrine to induce an increase in MAP of 20-30 mm Hg. From the simultaneously recorded data of Vmca and MAP, cerebral vascular resistance (CVR) was calculated as MAP/Vmca. Furthermore, the index of autoregulation (IOR) was calculated as DeltaCVR/DeltaMAP, where DeltaCVR = change in CVR and DeltaMAP = change in MAP. The test was performed twice for each condition on each patient: baseline and hypotension. The IOR during baseline was similar among the groups. During nitroglycerin- and prostaglandin E(1)-induced hypotension, IOR was not different from baseline. In contrast, during nicardipine-induced hypotension, IOR significantly decreased compared with baseline (0.37 +/- 0.08 versus 0.83 +/- 0.07, P < 0.01). In conclusion, nicardipine, but not nitroglycerin or prostaglandin E(1), significantly attenuates cerebral pressure autoregulation during propofol-fentanyl anesthesia. IMPLICATIONS: Vasodilators may influence cerebral autoregulation by changing cerebral vascular tone. Nicardipine, but not nitroglycerin or prostaglandin E(1), attenuated cerebral pressure autoregulation in normal adult patients during propofol-fentanyl anesthesia.     

Graded hypercapnia and cerebral autoregulation during sevoflurane or propofol anesthesia

BACKGROUND: Hypercapnia abolishes cerebral autoregulation, but little is known about the interaction between hypercapnia and autoregulation during general anesthesia. With normocapnia, sevoflurane (up to 1.5 minimum alveolar concentration) and propofol do not impair cerebral autoregulation. This study aimed to document the level of hypercapnia required to impair cerebral autoregulation during propofol or sevoflurane anesthesia. METHODS: Eight healthy subjects received a remifentanil infusion and were anesthetized with propofol (140 microg. kg-1. min-1) and sevoflurane (1.0-1.1% end tidal) in a randomized crossover study. Ventilation was adjusted to achieve incremental increases in arterial carbon dioxide partial pressure (Paco2) until autoregulation was impaired. Cerebral autoregulation was tested by increasing the mean arterial pressure (MAP) from 80 to 100 mmHg with phenylephrine while measuring middle cerebral artery flow velocity by transcranial Doppler. The autoregulation index, which has a value ranging from 0 to 1, representing absent to perfect autoregulation, was calculated, and an autoregulation index of 0.4 or less represented significantly impaired autoregulation. RESULTS: The threshold Paco2 to significantly impair cerebral autoregulation ranged from 50 to 66 mmHg. The threshold averaged 56 +/- 4 mmHg (mean +/- SD) during sevoflurane anesthesia and 61 +/- 4 mmHg during propofol anesthesia (P = 0.03). Carbon dioxide reactivity measured at a MAP of 100 mmHg was 30% greater than that at a MAP of 80 mmHg. CONCLUSIONS: Even mild hypercapnia can significantly impair cerebral autoregulation during general anesthesia. There is a significant difference between propofol anesthesia and sevoflurane anesthesia with respect to the effect of hypercapnia on cerebral autoregulation. This difference occurs at clinically relevant levels of Paco2. When inducing hypercapnia, carbon dioxide reactivity is significantly affected by the MAP.     

S(+)-ketamine/propofol maintain dynamic cerebrovascular autoregulation in humans

PURPOSE: This study investigates the effects of S(+)-ketamine and propofol in comparison to sevoflurane on dynamic cerebrovascular autoregulation in humans. METHODS: Twenty-four patients were randomly assigned to one of the following anesthetic protocols: group I (n=12): 2.5 mg.kg(-1)*hr(-1) S(+)-ketamine, 1.5-2.5 microg*mL(-1) propofol-target plasma concentration; group II (n=12): 2.0 MAC (4.0 %) sevoflurane. Patients were intubated and ventilated with O(2)/air (PaO(2)=0.33). Following 40 min of equilibration dynamic cerebrovascular autoregulation was measured and expressed as the autoregulatory index (ARI), describing the duration of cerebral hemodynamic recovery in relation to changes in mean arterial blood pressure. Statistics: Mann-Whitney U test (statistical significance was assumed when P <0.05). RESULTS: Dynamic cerebrovascular autoregulation was intact in all patients with S(+)-ketamine/propofol anesthesia as indicated by an ARI of 5.4 +/- 1.1. In contrast, dynamic cerebrovascular autoregulation was significantly delayed with 2.0 MAC sevoflurane (ARI=2.6 +/- 0.7) CONCLUSION: Dynamic cerebrovascular autoregulation is maintained with S(+)-ketamine/propofol-based total iv anesthesia. In contrast, 2.0 MAC sevoflurane delayed dynamic cerebrovascular autoregulation. This supports the use of S(+)-ketamine in combination with propofol in neurosurgical patients based on its neuroprotective potential along with maintained cerebrovascular physiology.     

Cerebral autoregulation in awake versus isoflurane-anesthetized rats

We evaluated regional cerebral and spinal cord blood flow in rats during isoflurane anesthesia. Tissue blood flow was measured in cerebral cortex, subcortex, midbrain, and spinal cord using radioactive microspheres. Blood flow autoregulation was measured within the following arterial blood pressure ranges (mm Hg): 1 = less than 50, 2 = 50-90, 3 = 90-130, 4 = 130-170, 5 = greater than 170. Arterial blood pressure was increased using phenylephrine infusion and decreased with ganglionic blockade and hemorrhage. Three treatment groups were studied: 1 = awake control, 2 = 1.0 minimum alveolar anesthetic concentration (MAC) isoflurane, 3 = 2.0 MAC isoflurane. Autoregulation was seen in awake rats from 50 to 170 mm Hg in all tissues. The autoregulatory coefficient (change in blood flow/change in blood pressure) was increased in midbrain and spinal cord during 1.0 MAC isoflurane and in all tissues during 2.0 MAC isoflurane (P less than 0.05). Within the arterial blood pressure range of 90-130 mm Hg, isoflurane produced the following changes in tissue blood flow (percent of awake control): 1.0 MAC isoflurane: cortex = 87% +/- 8% (P greater than 0.30), subcortex = 124% +/- 11% (P greater than 0.05), midbrain = 263% +/- 20% (P less than 0.001), spinal cord = 278% +/- 19% (P less than 0.001); 2.0 MAC isoflurane: cortex = 137% +/- 13% (P less than 0.05), subcortex = 272% +/- 24% (P less than 0.001), midbrain = 510% +/- 53% (P less than 0.001), spinal cord = 535% +/- 50% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Direct Cerebral Vasodilatory Effects of Sevoflurane and Isoflurane

Background: The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram.

Methods: Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 [mu]g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels.

Results: Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4 +/- 3 and 17 +/- 3% at 0.5 and 1.5 MAC sevoflurane; 19 +/- 3 and 72 +/- 9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P < 0.05). All patients required phenylephrine (100-300 [mu]g) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia.     

Relationship between minimum alveolar concentration and electroencephalographic bispectral index as well as spectral edge frequency 95 during isoflurane/epidural or sevoflurane/epidural anesthesia]

To investigate the relationship between minimum alveolar concentration (MAC) and electroencephalographic variables, we measured the bispectral index (BIS) and the spectral edge frequency 95 (SEF 95) in 17 patients undergoing elective surgery during isoflurane/epidural (n = 8) or sevoflurane/epidural (n = 9) anesthesia. Patients received 2.0 MAC end-tidal concentrations of isoflurane or sevoflurane, and the BIS and the SEF 95 were recorded after 15 min of an unchanged end-tidal concentration. The concentration of the inhalational agent was decreased to 1.2 MAC, and measurements were repeated again. During isoflurane anesthesia, the BIS increased significantly (3.6 +/- 3.9 at 2.0 MAC, 43.5 +/- 9.2 at 1.2 MAC [mean +/- SD]). In contrast, the BIS did not change significantly during sevoflurane anesthesia (35.3 +/- 8.4 at 2.0 MAC, 42.8 +/- 6.1 at 1.2 MAC). There were significant differences in the BIS and the SEF 95 at 2.0 MAC between isoflurane and sevoflurane groups. In contrast, the BIS and the SEF 95 showed no difference at 1.2 MAC between the groups. These findings suggest that different inhalational anesthetics may have different effects on the BIS and the SEF 95.     

Cerebrovascular reactivity to carbon dioxide is preserved during hypocapnia in children anesthetized with 1.0 MAC, but not with 1.5 MAC desflurane

PURPOSE: Maintenance of cerebrovascular reactivity to CO(2) (CCO(2)R) is important during neurosurgical anesthesia. This study was designed to determine the effect of different desflurane concentrations on CCO(2)R in children. METHODS: Children undergoing urological surgery were enrolled. Anesthesia was induced with sevoflurane in air/oxygen. After intubation, sevoflurane was switched to desflurane. Analgesia was provided with an epidural neuraxial block. Mechanical ventilation was adjusted to an initial EtCO(2) of 30 mmHg. Exogenous CO(2) was used to achieve an EtCO(2) of 40 and 50 mmHg. Patients were randomized to the sequence of desflurane concentration (1.0 and 1.5 MAC) and the EtCO(2). Transcranial Doppler was used to measure middle cerebral artery blood flow velocity (Vmca). Five minutes were allowed to reach steady state after each change in EtCO(2) and 15 min after changing the desflurane concentration. RESULTS: Sixteen patients were studied. The mean age and weight were 3.5 +/- 1.5 yr and 14.4 +/- 3.1 kg, respectively. Mean arterial pressure remained stable throughout the study, while at an EtCO(2) of 50 mmHg, heart rate decreased at both desflurane concentrations (P < 0.05). At 1.0 MAC, Vmca increased from 30 to 40 mmHg (P < 0.05), but not from 40 to 50 mmHg EtCO(2). At 1.5 MAC, Vmca increased between 30 and 50 mmHg (P < 0.05). CONCLUSION: CCO(2)R is preserved during hypocapnia in children anesthetized with 1.0 MAC, but not with 1.5 MAC desflurane. The lack of further increase in Vmca at higher EtCO(2) concentrations implies that desflurane may cause significant cerebral vasodilatation in children. This may have important implications in children with reduced intracranial compliance.     

Graded Hypercapnia and Cerebral Autoregulation during Sevoflurane or Propofol Anesthesia

Background: Hypercapnia abolishes cerebral autoregulation, but little is known about the interaction between hypercapnia and autoregulation during general anesthesia. With normocapnia, sevoflurane (up to 1.5 minimum alveolar concentration) and propofol do not impair cerebral autoregulation. This study aimed to document the level of hypercapnia required to impair cerebral autoregulation during propofol or sevoflurane anesthesia.

Methods: Eight healthy subjects received a remifentanil infusion and were anesthetized with propofol (140 [mu]g [middle dot] kg-1 [middle dot] min-1) and sevoflurane (1.0-1.1% end tidal) in a randomized crossover study. Ventilation was adjusted to achieve incremental increases in arterial carbon dioxide partial pressure (Paco2) until autoregulation was impaired. Cerebral autoregulation was tested by increasing the mean arterial pressure (MAP) from 80 to 100 mmHg with phenylephrine while measuring middle cerebral artery flow velocity by transcranial Doppler. The autoregulation index, which has a value ranging from 0 to 1, representing absent to perfect autoregulation, was calculated, and an autoregulation index of 0.4 or less represented significantly impaired autoregulation.

Results: The threshold Paco2 to significantly impair cerebral autoregulation ranged from 50 to 66 mmHg. The threshold averaged 56 +/- 4 mmHg (mean +/- SD) during sevoflurane anesthesia and 61 +/- 4 mmHg during propofol anesthesia (P = 0.03). Carbon dioxide reactivity measured at a MAP of 100 mmHg was 30% greater than that at a MAP of 80 mmHg.     

The epileptogenic properties of the volatile anesthetics sevoflurane and isoflurane in patients with epilepsy

No study comparing epileptogenicity of sevoflurane to other volatile anesthetics has been performed. We compared the epileptogenic properties of sevoflurane to isoflurane in patients with epilepsy. In 24 mentally and/or physically disabled patients, 12 with epilepsy and 12 without epilepsy, electroencephalograms were recorded under anesthesia with 1.0 minimum alveolar anesthetic concentration (MAC), 1.5 MAC, and then 2.0 MAC sevoflurane or isoflurane under three ventilatory conditions: (A) 100% oxygen, and end-tidal CO(2) partial pressure (ETCO(2)) = 40 mm Hg, (B) 50% oxygen, 50% nitrous oxide, ETCO(2) = 40 mm Hg, and (C) 100% oxygen, ETCO(2) = 20 mm Hg. Spike activity was evaluated as a spike-and-wave index (% durations of spike and wave). The spike-and-wave index increased (P<0.05) from 1.99%+/-0.96% during 1.0 MAC sevoflurane to 6.14% +/- 4.45% during 2.0 MAC sevoflurane in (A) in the epilepsy group, while no spike activity was observed in the nonepilepsy group. Only a few spikes were observed under isoflurane anesthesia, 0.04% +/- 0.04% in (A), with no spikes in (B) and (C). Supplementation with 50% nitrous oxide or hyperventilation (P<0.05) suppressed the occurrence of spikes. Sevoflurane has a stronger epileptogenic property than isoflurane, but nitrous oxide or hyperventilation counteracts this specific epileptogenic property. Implications: The stronger epileptogenicity of sevoflurane than isoflurane was confirmed in a controlled study in patients with epilepsy. Hyperventilation and supplementation of nitrous oxide under sevoflurane anesthesia suppressed epileptogenicity. A combination of sevoflurane and nitrous oxide may be a safer method for seizure-prone patients than the use of sevoflurane alone.     

Sevoflurane induces less cerebral vasodilation than isoflurane at the same A-line autoregressive index level

BACKGROUND: The use of sevoflurane in neuroanesthesia is still under debate. Comparison of dose-dependent vasodilatory properties between sevoflurane and isoflurane, the more traditional neuroanesthetic agent, requires comparable dosing of the agents. A-line autoregressive index (AAI) provides reproducible individual measurement of anesthetic depth. METHODS: Sevoflurane and isoflurane, in randomized order, were titrated to a stable AAI of 15-20 in each of 18 ASA I or II patients. The mean flow velocity (Vmca) and pulsatility index (PI) in the middle cerebral artery were measured with transcranial Doppler at an end-tidal CO2 of 4.5%. RESULTS: For sevoflurane Vmca was 18% lower [95% confidence interval (CI) 12-22%; P < 0.00001] and PI was 23% higher (95% CI 12-33%; P = 0.0013) than for isoflurane. Mean arterial blood pressure did not differ between the two agents. The minimum alveolar concentration (MAC) fraction necessary to reach the intended AAI level was 13% higher (95% CI 5-20%; P = 0.0079) with sevoflurane than with isoflurane. CONCLUSION: Sevoflurane induced less cerebral vasodilation than isoflurane at the same depth of anesthesia, measured by AAI, and hence seems more favorable for clinical neuroanesthesia. In our opinion the difference between sevoflurane and isoflurane in the MAC fraction required to attain the same AAI level demonstrates the limitations of MAC in defining the level of anesthesia.     

Preservation of the Ratio of Cerebral Blood Flow/Metabolic Rate for Oxygen during Prolonged Anesthesia with Isoflurane, Sevoflurane, and Halothane in Humans

Background: In several animal studies, an increase in cerebral blood flow (CBF) produced by volatile anesthetics has been reported to resolve over time during prolonged anesthesia. It is important to investigate whether this time-dependent change of CBF takes place in humans, especially in clinical situations where surgery is ongoing under anesthesia. In this study, to evaluate the effect of prolonged exposure to volatile anesthetics (isoflurane, sevoflurane, and halothane), the CBF equivalent (CBF divided by cerebral metabolic rate for oxygen (CMRO2)) was determined every 20 min during anesthesia lasting more than 4 h in patients.

Methods: Twenty-four surgical patients were assigned to three groups at random to receive isoflurane, sevoflurane, or halothane (8 patients each). End-tidal concentration of the selected volatile anesthetic was maintained at 0.5 and 1.0 MAC before surgery and then 1.5 MAC for the 3 h of surgical procedure. Normothermia and normocapnia were maintained. Mean arterial blood pressure was kept above 60 mmHg, using phenylephrine infusion, if necessary. CBF equivalent was calculated every 20 min as the reciprocal of arterial-jugular venous oxygen content difference.

Results: CBF equivalent at 0.5 MAC of isoflurane, halothane, and sevoflurane was 21+/-4, 20+/-3, and 21+/-5 ml blood/ml oxygen, respectively. All three examined volatile anesthetics significantly (P < 0.01) increased CBF equivalent in a dose-dependent manner (0.5, 1.0, 1.5 MAC). At 1.5 MAC, the increase of CBF equivalent with all anesthetics was maintained increased with minimal fluctuation for 3 h. The mean value of CBF equivalent at 1.5 MAC in the isoflurane group (45+/-8) was significantly (P < 0.01) greater than those in the halothane (32+/-8) and sevoflurane (31+/-8) groups. Electroencephalogram was found to be relatively unchanged during observation periods at 1.5 MAC.