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.     

The lower limit of cerebral autoregulation in children during sevoflurane anesthesia

In adults, the lower limit of cerebral autoregulation (LLA) is generally considered to be a mean arterial pressure (MAP) of 60 mmHg. The LLA in healthy children has not been identified. The aim of this report is to describe the LLA in anesthetized children and relate it to age. Static cerebral autoregulation testing was performed in children 6 months to 14 years of age during <1 MAC sevoflurane anesthesia. Mean middle cerebral artery flow velocities (Vmca) were continuously measured using transcranial Doppler ultrasonography. MAP was increased with infusion of intravenous phenylephrine incrementally titrated to the greater of either: 1) 20% above baseline MAP or 2) 80 mmHg (<9 years), 90 mmHg (9-14 years). The LLA was defined by the point where the two linear regression lines fitting the Vmca/MAP crossed. The lower limit reserve (LLR) and autoregulatory reserve (ARR%) were defined as follows: LLR=Baseline MAP-LLA; ARR (%)=(LLR/Baseline MAP)x100. There were 13 subjects <2 years of age (group 1), 13 subjects 2 to 5 years of age (group 2), 14 subjects 6 to 9 years of age (group 3), and 13 subjects 10 to 14 years of age (group 4). Older children (groups 3 and 4) had a higher baseline MAP compared with younger children (groups 1 and 2) (82 +/- 10 mmHg vs. 70 +/- 10 mmHg, respectively; P=0.0001). However, there was no difference in LLA (59 +/- 17 mmHg vs. 60 +/- 8 mmHg; P=0.6) between older and younger children. Consequently, the LLR was greater in older children compared with younger children (25 +/- 12 mmHg vs. 12 +/- 10 mmHg, respectively; P=0.0007). Similarly, the ARR was significantly higher in older children compared with younger children (30% +/- 16% vs. 16% +/- 12%; P=0.002). In this study, we found no age-related differences in the LLA. Older children had a greater LLR and ARR compared with young children. The baseline MAP in young children may rest close to the LLA. These findings may have implications for managing hemodynamics in anesthetized children at risk for secondary brain injury.     

The effects of sevoflurane on cerebral blood flow autoregulation and flow-metabolism coupling during cardiopulmonary bypass

Background: Previous studies on non‐cardiac surgical patients have shown that cerebral pressure‐flow autoregulation and cerebral flow‐metabolism coupling are maintained with sevoflurane. The effects of sevoflurane on cerebral blood flow (CBF) autoregulation and flow‐metabolism coupling during cardiopulmonary bypass (CPB) have not been studied previously. Methods: The effects of sevoflurane‐induced burst suppression, monitored with electroencephalography (EEG), on cerebral blood flow velocity (CBFV), cerebral oxygen extraction (COE) and flow autoregulation, were studied in 16 patients undergoing cardiac surgery. The experimental procedure was performed during non‐pulsatile CPB with mild hypothermia (34 °C) in fentanyl/droperidol‐anesthetized patients. Middle cerebral artery transcranial Doppler flow velocity, right jugular vein bulb oxygen saturation and jugular venous pressure were measured continuously. Autoregulation was tested during changes in the mean arterial pressure (40–90 mmHg), induced by sodium nitroprusside and norepinephrine before (control), and during additional sevoflurane administration, in a dose that resulted in an EEG burst‐suppression level of 4–6/min. Results: Sevoflurane, at an inspired concentration of 3.36±0.03%, induced a 17% decrease in CBFV (P<0.05) and a 22% decrease in COE (P<0.05) compared with the control. The slope of the positive relationship between CBFV and cerebral perfusion pressure was steeper with sevoflurane (P<0.01) compared with control measurements, as was the slope of the negative relationship between CPP and COE (P<0.01). Conclusion: Burst‐suppression doses of sevoflurane exert an intrinsic cerebral vasodilatory effect, which impairs CBF autoregulation during mildly hypothermic CPB. Furthermore, during sevoflurane administration, CBF is in excess relative to oxygen demand, indicating a partial loss of the cerebral flow‐metabolism coupling.     

Response to CO2 and autoregulation of cortical cerebral blood flow during isoflurane anesthesia

Response to CO2 and autoregulation of cortical cerebral blood flow (CBF) during isoflurane anesthesia were studied in 10 patients undergoing neurosurgery. The patients were anesthetized with 0.5 to 1.2% end-tidal isoflurane and 66% nitrous oxide in oxygen. The CBF was measured by thermal diffusion using a flow probe with a Peltier stack. PaCO2 was controlled to produce hypocarbia, normocarbia and hypercarbia by changing tidal volume and respiratory rate. Arterial blood pressure was altered. Hypotension was achieved by intravenous infusion of trimetaphan and hypertension was induced by intravenous administration of metaraminol. During isoflurane anesthesia the response to CO2 of CBF was kept at PaCO2 between 27.8 and 53.9 mmHg. The following relationship was obtained. CBF = 2.54 x PaCO2-53.0, r = 0.59, n = 131 The autoregulation of CBF was evaluated in 7 patients, and in 2 patients, the autoregulation of CBF was abolished.     

Influence of anesthesia on autoregulation of the cerebral blood flow.

Autoregulation of the cerebral blood flow is a wellknown fact. In normal man the arterial pressure can vary from 80 mm Hg to 150 mm Hg without a change in the normal cerebral blood flow of 50 ml/100 g/min. The mechanism which is responsible for this autoregulation is not clearly understood. Several theories were proposed to explain this phenomenon. 1. The tissue pressure increases with an increase of the arterial pressure. A mechanical process should neutralize an increase of the cerebral blood flow. 2. The metabolic theory says that a decrease of the blood pressure, without a change of metabolism, involves an increase of the PaCO2, and a decrease of the PaO2. Those two factors provoke a decrease of the vascular tone. 3. The myogenic theory explains autoregulation by the fact that a change of the transmural pressure in the small vessels, involves a change in the activity of the smooth muscles of the vessels. 4. The exact mechanism of the autonomic nervous system in the autoregulation of the cerebral blood flow is still obscure. In some pathological conditions autoregulation is completely lost or is functioning not optimal: hypoxia, hypercapnia and brain contusion. We have measured the cerebral blood flow before and after an intravenous injection of 5 mg thiopental (Pentothal) on occasion of a carotid angiography in man. We noticed a decrease of the cerebral blood flow and at the same moment a decrease of the arterial pressure. We thought that maybe barbiturates could influence autoregulation. Our results could not prove this hypothesis. For ethical reasons we could not make the necessary measurements to prove or to reject this hypothesis (i.e. intracranial pressure, deep controlled hypotension). In the literature there are arguments which support this hypothesis although most workers found an intact autoregulation after a barbiturate anesthesia. Some workers saw that the increase of the cerebral blood flow by increasing the PaCO2 was depressed by barbiturates and exhausted by halothane and cyclopropane. As autoregulation is a more vulnerable mechanism than CO2 reactivity as seen in clinical situations, it could be true that anesthetics do influence autoregulation.     

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.     

The effects of sevoflurane and halothane anesthesia on cerebral blood flow velocity in children

We compared cerebral blood flow velocity during anesthesia with sevoflurane and halothane in 23 children admitted for elective surgery (age, 0.4-9.7 yr; median age, 1.9 yr; ASA physical status I-II). Inhaled induction was performed in a randomized sequence with sevoflurane or halothane. Under steady-state conditions, cerebral blood flow velocity (systolic [V(s)], mean [V(mn)], and diastolic [VD]) were measured by a blinded investigator using transcranial pulsed Doppler ultrasonography. The anesthetic was then changed. CBFV measurements were repeated after washout of the first anesthetic and after steady-state of the second (equivalent minimal alveolar concentration to first anesthetic). The resistance index was calculated. VD and V(mn) were significantly lower during sevoflurane (V(mn) 1.35 m/s) than during halothane (V(mn) 1.50 m/s; P = 0.001), whereas V(s) was unchanged. The resistance index was lower during halothane (P < 0.001). Our results indicate lower vessel resistance and higher mean velocity during halothane than during sevoflurane. IMPLICATIONS: The mean cerebral blood flow velocity is significantly decreased in children during inhaled anesthesia with sevoflurane than during halothane. This might be relevant for the choice of anesthetic in children with risk of increased intracranial pressure, neurosurgery, or craniofacial osteotomies.     

The effect of sevoflurane on dynamic cerebral blood flow autoregulation assessed by spectral and transfer function analysis

Sevoflurane reduces autonomic neural control, which plays a significant role in cerebral autoregulation. Therefore, we hypothesized that sevoflurane influences cerebral autoregulation. We investigated the effects of sevoflurane on dynamic cerebral blood flow (CBF) autoregulation by using spectral and transfer function analysis between blood pressure variability and CBF velocity variability. Eleven healthy male subjects received 0.5%, 1.0%, and 1.5% sevoflurane via facemask. Dynamic cerebral autoregulation was evaluated by transfer function gain, phase, and coherence between CBF velocity in the middle cerebral artery measured by transcranial Doppler, and blood pressure in the radial artery. Coherence in the very low-frequency range (0.02-0.07 Hz) increased above 0.5 during administration of 0.5% and 1.0% sevoflurane. Transfer function gain in this frequency range (0.02-0.07 Hz), as an index of dynamic cerebral autoregulation, increased significantly with 0.5% and 1.0% sevoflurane. Transfer function gain and coherence in the low- and high-frequency ranges, however, remained unchanged during administration of sevoflurane. These results suggest that sevoflurane impairs dynamic cerebral autoregulation in the very-low-frequency range even with small concentrations, whereas dynamic cerebral autoregulation in the low- and high-frequency ranges remained unchanged.     

七氟醚和异丙酚复合麻醉下妇科腹腔镜手术患者脑血流量和颅内压的比较

Objective To compare the cerebral blood flow (CBF) and intracranial pressure (ICP) during laparoscopic gynecologic surgery performed under propofol and sevoflurane combined anesthesia.Methods Forty ASAⅠ orⅡ patients aged 20-59 yr weighing 44-69 kg were randomly divided into 2 groups(n=20 each):propofol group (group P) and sevoflurane group (group S).Anesthesia was induced with TCI of propofol (Ce 4μg/ml) in group P or 8% sevoflurane in group S combined with TCI of remifentanil (Ce 6 ng/ml).Tracheal intubation was facilitated with cis-atracurium 0.15 mg/kg.The patients were mechanically ventilated.PETCO2 was maintained at 35-40 mm Hg.Anesthesia was maintained with TCI of propofol or sevoflurane.inhalation combined with TCI of remifentanil.BIS value was maintained at 45-50 by adjusting Ce of propofol or concentration of sevoflurane.Intraabdominal pressure (IAP) was maintained at 12-14 mm Hg.Transcranial Doppler monitoring wag used.Cerebral blood flow velocity (CBFV) and pulsatility index (PI) were recorded at 5 min after supine position(T1)and 5 min after supine lithotomy position before induction(T2),while tracheal tube was being inserted(T3),5 min after tracheal intubation(T4),immediately and 15 min after abdominal CO2 iusnfflation in trendelenburglithotomy position (T5,T6) and at 10 min after deflation of abdomen(T7).Results CBFV was significandy decreased at T3,T4 and T7 in group P and at T4 and T7 in group S as compared with the baseline at T1.CBFV at T3 was significantly lower in group P than in group S.PI at T3,T4 was significantly decreased in group P as compared with the baseline at T1 and was significantly lower than in group S.PI at T5,6 was significantly increased as compared with the baseline in both groups but was not significantly different between the 2 groups.Conclusion When combined with remifentanil.propofol could decrease CBF and ICP while sevoflurane has no significant effect on CBF and ICP after induction.CBF and ICP are significantly increased in both groups after abdominal CO2 insufflation.     

七氟醚和异丙酚复合麻醉下妇科腹腔镜手术患者脑血流量和颅内压的比较

目的 比较七氟醚和异丙酚复合麻醉下妇科腹腔镜手术患者的脑血流量(CBF)和颅内压(ICP).方法 择期拟行妇科腹腔镜手术患者40例,年龄20～59岁,体重44～69kg,ASA Ⅰ或Ⅱ级,随机分为2组(n=20):七氟醚复合麻醉组(S组)和异丙酚复合麻醉组(P组).麻醉诱导:S组吸人8%七氟醚,P组TCI异丙酚(Ce 4μg/ml),两组均TCI瑞芬太尼(Ce 6ng/ml),睫毛反射消失后,静脉注射顺阿曲库铵0.15mg/kg,BIS<45时行气管插管.麻醉诱导后瑞芬太尼Ce下调为3 ng/ml,调节异丙酚Ce和七氟醚吸人浓度,维持BIS 45～50,于麻醉诱导前水平仰卧位稳定后5 min(T1)、水平截石位稳定后5 min(T2)、气管插管后即刻(T3)、气管插管后5 min(T4)、气腹头低位后即刻(T5)、气腹头低位后15 min(T6)及气腹放气后10 min(T7)时采用经颅多普勒超声测定大脑中动脉脑血流速率(CBFV)和搏动指数(PI).结果 与T1时比较,P组T3,4,7时CBFV降低,T3,4时P1降低,S组T4,7时CBFV降低,两组T5,6时PI升高(P<0.05);与T4时比较,两组T5,6时CBFV升高(P<0.05);与S组比较,P组T3时CBFV降低,T3,4时PI降低(P<0.05).结论 与七氟醚复合麻醉相比,异丙酚复合麻醉下妇科腹腔镜手术患者麻醉诱导后CBF和ICP明显降低;气腹后CBF和ICP均升高.     

七氟醚和异丙酚复合麻醉下妇科腹腔镜手术患者脑血流量和颅内压的比较

Objective To compare the cerebral blood flow (CBF) and intracranial pressure (ICP) during laparoscopic gynecologic surgery performed under propofol and sevoflurane combined anesthesia.Methods Forty ASAⅠ orⅡ patients aged 20-59 yr weighing 44-69 kg were randomly divided into 2 groups(n=20 each):propofol group (group P) and sevoflurane group (group S).Anesthesia was induced with TCI of propofol (Ce 4μg/ml) in group P or 8% sevoflurane in group S combined with TCI of remifentanil (Ce 6 ng/ml).Tracheal intubation was facilitated with cis-atracurium 0.15 mg/kg.The patients were mechanically ventilated.PETCO2 was maintained at 35-40 mm Hg.Anesthesia was maintained with TCI of propofol or sevoflurane.inhalation combined with TCI of remifentanil.BIS value was maintained at 45-50 by adjusting Ce of propofol or concentration of sevoflurane.Intraabdominal pressure (IAP) was maintained at 12-14 mm Hg.Transcranial Doppler monitoring wag used.Cerebral blood flow velocity (CBFV) and pulsatility index (PI) were recorded at 5 min after supine position(T1)and 5 min after supine lithotomy position before induction(T2),while tracheal tube was being inserted(T3),5 min after tracheal intubation(T4),immediately and 15 min after abdominal CO2 iusnfflation in trendelenburglithotomy position (T5,T6) and at 10 min after deflation of abdomen(T7).Results CBFV was significandy decreased at T3,T4 and T7 in group P and at T4 and T7 in group S as compared with the baseline at T1.CBFV at T3 was significantly lower in group P than in group S.PI at T3,T4 was significantly decreased in group P as compared with the baseline at T1 and was significantly lower than in group S.PI at T5,6 was significantly increased as compared with the baseline in both groups but was not significantly different between the 2 groups.Conclusion When combined with remifentanil.propofol could decrease CBF and ICP while sevoflurane has no significant effect on CBF and ICP after induction.CBF and ICP are significantly increased in both groups after abdominal CO2 insufflation.     

Hemodynamic and organ blood flow responses to halothane and sevoflurane anesthesia during spontaneous ventilation.

This study compared systemic hemodynamic and organ blood flow responses to equipotent concentrations of halothane and sevoflurane during spontaneous ventilation in the rat. The MAC values for halothane and sevoflurane were determined. Cardiac output and organ blood flows were measured using radiolabeled microspheres. Measurements were obtained in awake rats (control values) and at 1.0 MAC halothane or sevoflurane. The MAC values (mean +/- SEM) for halothane and sevoflurane were 1.10% +/- 0.05% and 2.40% +/- 0.05%, respectively. The PaCO2 increased to a similar extent in both groups compared with control values. During halothane anesthesia, heart rate decreased by 12% (P < 0.01), cardiac index by 26% (P < 0.01), and mean arterial blood pressure by 18% (P < 0.01) compared with control values. Stroke volume index and systemic vascular resistance did not change. During sevoflurane anesthesia, hemodynamic variables remained unchanged compared with control values. Coronary blood flow decreased by 21% (P < 0.01) and renal blood flow by 18% (P < 0.01) at 1.0 MAC halothane, whereas both remained unchanged at 1.0 MAC sevoflurane. Cerebral blood flow increased to a greater extent with halothane (63%; P < 0.01) than with sevoflurane (35%; P < 0.05). During halothane anesthesia, hepatic arterial blood flow increased by 48% (P < 0.01), whereas portal tributary blood flow decreased by 28% (P < 0.01). During sevoflurane anesthesia, hepatic arterial blood flow increased by 70% (P < 0.01) without a concomitant reduction in portal tributary blood flow. Total liver blood flow decreased only with halothane (16%; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential effects of hyperventilation on cerebral blood flow velocity after tourniquet deflation during sevoflurane, isoflurane, or propofol anesthesia

The purpose of this study was to compare the degree of increase in middle cerebral artery (MCA) blood flow velocity after tourniquet deflation when modulating hyperventilation during orthopedic surgery under sevoflurane, isoflurane, or propofol anesthesia. Twenty-four patients undergoing elective orthopedic surgery were randomly divided into sevoflurane, isoflurane, and propofol groups. Anesthesia was maintained with sevoflurane, isoflurane, or propofol administration with 33% oxygen and 67% nitrous oxide at anesthetic drug concentrations adequate to maintain bispectral values between 45 and 50. A 2.0-MHz transcranial Doppler probe was attached to the patient’s head at the temporal window, and mean blood flow velocity in the MCA (V _mca) was continuously measured. The extremity was exsanguinated with an Esmarch bandage, and the pneumatic tourniquet was inflated to a pressure of 450 mmHg. Arterial blood pressure, heart rate, V _mca and arterial blood gases were measured every minute for 10 min after release of the tourniquet in all three groups. Immediately after tourniquet release, the patients’ respiratory rates were increased to tightly maintain end-tidal carbon dioxide (PetCO₂) at 35 mmHg. No change in partial pressure of carbon dioxide in arterial blood (PaCO₂) was observed pre- and posttourniquet deflation in any of the three groups. Increase in V _mca in the isoflurane group was greater than that in the other two groups after tourniquet deflation. In addition, during the study period, no difference in V _mca after tourniquet deflation was observed between the propofol and sevoflurane groups. Hyperventilation could prevent an increase in V _mca in the propofol and sevoflurane groups after tourniquet deflation. However, hyperventilation could not prevent an increase in V _mca in the isoflurane group.     

Regional cerebral blood flow responses to hyperventilation during sevoflurane anaesthesia studied with PET

Background: Arterial carbon dioxide tension (PaCO₂) is an important factor controlling cerebral blood flow (CBF) in neurosurgical patients. It is still unclear whether the hypocapnia‐induced decrease in CBF is a general effect on the brain or rather linked to specific brain regions. We evaluated the effects of hyperventilation on regional cerebral blood flow (rCBF) in healthy volunteers during sevoflurane anaesthesia measured with positron emission tomography (PET). Methods: Eight human volunteers were anaesthetized with sevoflurane 1 MAC, while exposed to hyperventilation. During 1 MAC sevoflurane at normocapnia and 1 MAC sevoflurane at hypocapnia, one H₂¹⁵O scan was performed. Statistical parametric maps and conventional regions of interest analysis were used for estimating rCBF differences. Results: Cardiovascular parameters were maintained constant over time. During hyperventilation, the mean PaCO₂ was decreased from 5.5 ± 0.7 to 3.8 ± 0.9 kPa. Total CBF decreased during the hypocapnic state by 44%. PET revealed wide variations in CBF between regions. The greatest values of vascular responses during hypocapnia were observed in the thalamus, medial occipitotemporal gyrus, cerebellum, precuneus, putamen and insula regions. The lowest values were observed in the superior parietal lobe, middle and inferior frontal gyrus, middle and inferior temporal gyrus and precentral gyrus. No increases in rCBF were observed. Conclusions: This study reports highly localized and specific changes in rCBF during hyperventilation in sevoflurane anaesthesia, with the most pronounced decreases in the sub cortical grey matter. Such regional heterogeneity of the cerebral vascular response should be considered in the assessment of cerebral perfusion reserve during hypocapnia.