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Departments of *Anesthesiology, Pediatrics, and Neurological Surgery, University of Washington, Seattle, Washington
Address correspondence and reprint requests to Irene Rozet, MD, Assistant Professor, Harborview Medical Center, Box 359724, 325 Ninth Avenue, Seattle, Washington 98104-2499. Address e-mail to i_rozet{at}hotmail.com.
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Abstract |
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Introduction |
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Cerebral autoregulation is the phenomenon in which cerebral blood flow (CBF) remains nearly constant despite changes in cerebral perfusion pressure within a range generally considered to be 50–150 mm Hg. Much of the data regarding effects of anesthetics on cerebral autoregulation and CO2 reactivity (CO2R) comes from examination of the anterior circulation. There are no data regarding cerebral autoregulation and CO2R in the posterior cerebral circulation under general anesthesia. Moreover, there are reports of anatomical (1) and physiological (2–4) differences in the cerebral vasculature between anterior and posterior circulation in humans. Studies on healthy volunteers suggested better CO2R in brain regions of posterior circulation compared with anterior circulation (4). The influence of anesthetics on the different brain areas may be heterogeneous, depending on the drug and the dose (5–7). Kaisti et al. (5), measuring regional CBF using a positron emission tomographic (PET) scan, observed changes in CBF under 2 MAC sevoflurane to be opposite in cerebellum and frontal lobes, with a significant increase in cerebellar CBF, along with significant decrease in frontal CBF.
Differences in CO2R in different brain regions could play an important role in pathological conditions during anesthesia. The knowledge of cerebral vasoactive capacity of posterior circulation could be especially helpful in the neurosurgical population with pathologic processes in the posterior fossa, such as a cerebellar tumor, and might alter anesthetic management.
The aim of the present study was to compare cerebral autoregulation and CO2R between the anterior and posterior cerebral circulation during sevoflurane anesthesia in healthy humans.
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Methods |
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After premedication with IV midazolam 1–2 mg, general anesthesia was induced with IV propofol 2–2.5 mg/kg and muscle relaxation was achieved with IV vecuronium 0.1 mg/kg. All patients received tracheal intubation and mechanical ventilation with an inspired mixture of air/oxygen (Fio2 = 0.3–0.4). General anesthesia was maintained with sevoflurane (end-tidal [ET] sevoflurane 1.0–1.2 vol%) and remifentanil infusion (0.125–0.375 µg · kg–1 · min–1).
After induction of general anesthesia, a 20-gauge catheter was inserted percutaneously into the radial artery for continuous arterial blood pressure (MAP) monitoring and arterial blood sampling. Patients were placed either in the lateral decubitus (n = 8) or supine (n = 1) position.
Using transcranial Doppler (TCD) ultrasonography to measure CBF velocities, middle cerebral artery (MCA) and BA were simultaneously insonated. In a randomized sequence cerebral autoregulation and CO2R were tested in each subject during steady-state anesthesia and steady-state surgical stimulation (as reflected by unchanged CBF velocity for 5 min before study). Between studies MAP and CBF velocities were allowed to return to baseline at normocapnia (Paco2 = 40 mm Hg).
Temperature was monitored using an esophageal temperature probe and kept between 36°C–37°C using forced air warming (Bair Hugger Model 500/OR; Arizant Healthcare, Eden Prairie, MN), and warmed IV fluids. Arterial blood gases and hematocrit were measured using an automated blood gas analyzer (ABL-500; Radiometer, Copenhagen, Denmark).
Right or left MCA and BA were insonated using TCD (Multi-Dop, DWL Elektronische Systeme GmbH, Langerach 4, D-7767 Sipplingen, Germany), and 2 mHz TCD probes were fixed using a frame (8). The MCA probe was fixed directly to the head frame, and the probe over the BA was fixed with a custom-designed rubberband attached to the frame. In two patients, BA insonation could not be maintained using the frame and was performed with a hand-held probe. The MCA was insonated at approximately 5 cm by tracking the vessel. After finding the optimal signal, it was tracked, usually to 4 cm, to confirm identification. The BA was insonated through the foramen magnum at a depth of 8 cm or more with identification of the optimal signal. MAP and mean CBF velocities in the MCA (Vmca) and BA (Vba) were continuously measured and recorded throughout the study and saved for off-line analysis.
Cerebral autoregulation was tested by increasing MAP by 20 mm Hg from the baseline during normocapnia as previously described (9). At a Paco2 of 40 mm Hg, MAP was slowly increased from 80 to 100 mm Hg using a 1% phenylephrine infusion. Vmca and Vba were recorded at two levels of MAP, and the cerebral autoregulation index (ARI) was calculated for the MCA (ARImca) and for the BA (ARIba) according to the standard equation (10): ARI = [(R2 – R1)/R1]/[(MAP2 – MAP1)/MAP1], where R is estimated cerebral vascular resistance, calculated by R = MAP/V (Vmca or Vba). Subscripts 1 and 2 refer to measurements at the lower and higher MAP, respectively, in our study at MAP = 80 mm Hg and MAP = 100 mm Hg, respectively.
ARI is a dimensionless value that ranges between 0 and 1.0, where ARI of 1.0 indicates perfect autoregulation, meaning no change in CBF velocity with the change of MAP, and ARI of zero indicates absent autoregulation, when an increase in CBF velocity is directly proportional to an increase in MAP.
Vmca and Vba were measured at 3 different levels of Paco2: approximately 30 mm Hg, 40 mm Hg, and 50 mm Hg, which were adjusted in random order by manipulating mechanical ventilation, guided by ETco2. After 3–4 min of stabilization of the target ETco2, arterial blood samples were taken for measurement of Paco2. Paco2 was considered to be acceptable if it did not differ from the target Paco2 level by 2–3 mm Hg. The test was performed at MAP of 80 mm Hg, which was maintained with the titration of phenylephrine infusion during constant remifentanil infusion.
Sample size calculation, which was performed based on a 30% expected difference in ARI between Vmca and Vbas (
of 0.05 and ß of 0.8), suggested a sample size of 6 patients.
Student’s t-test was used to compare ARImca and ARIba. Exponential and linear regression models were used for determination of CO2R in every patient, and R squares between exponential and linear regression were compared. The data fit both methods of analysis without a difference, and linear regression analysis was chosen for final analysis of CO2R. A P value < 0.05 was considered significant. Linear random effects regression was used to model the association between Vmca and Vba and Paco2. The model includes a subject level random effect to account for repeated measures within subjects. The main effects for Paco2 and vascular anatomy, and their interactions were investigated. All hypotheses were tested using Wald statistics. The data were analyzed using STATA statistical software version 8.0 (STATA Corp., College Station, TX).
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Results |
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An autoregulation test was performed at Paco2 of 39 ± 2 mm Hg and ET concentration of sevoflurane of 1.2% ± 0.2%. With the increase of MAP from 85 ± 5 mm Hg to 109 ± 3 mm Hg (P < 0.0001), CBF velocity in MCA and BA increased slightly (P = 0.002 for Vmca; P = 0.006 for Vba) (Table 1), but ARI was within the normal range in both arteries, and there was no difference between the 2 circulations: ARImca = 0.72 ± 0.2, ARIba = 0.66 ± 0.2, P = 0.5. A ARI > 0.4 is considered to be normal.
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A CO2R test was performed at MAP of 81 ± 4 mm Hg and ET sevoflurane of 1.2 ± 0.2 mm Hg. Vmca and Vba were recorded at Paco2 of 30 ± 2.8 mm Hg (hypocapnia), 39.4 ± 2.6 mm Hg (normocapnia), and 48.7 ± 2.8 mm Hg (hypercapnia).
In all patients, an increase of Paco2 led to increased Vmca and Vba (Fig. 1, Fig. 2). The data from both linear regression and exponential analysis showed no difference in R squares between the two methods. Since most studies in anesthesia literature report CO2R in % per mm Hg, we chose the method of linear regression analysis. For MCA, linear regression analysis revealed a slope of 1.7 cm/s/mm Hg Paco2 (4.09 ± 0.68%/mm Hg Paco2), which was not different from a slope of 1.5 cm/s/mm Hg Paco2 (4.66 ± 0.78%/mm Hg Paco2) for BA. As expected, the mean velocity in the MCA was higher than the mean velocity in the BA (P < 0.05) (Fig. 2). As shown in Figure 2, despite the difference in baseline CBF velocities between anterior and posterior circulation, the relationship between CBF velocity and Paco2 appears to be the same (P = 0.83 for test of interaction) for the 2 circulations.
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Discussion |
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This is the first study evaluating autoregulation and CO2R of the BA in comparison to the MCA under general anesthesia.
All previous research on the physiology of cerebral autoregulation under general anesthesia has been focused on the anterior circulation. CBF studies, using either nitrous oxide wash-in or xenon washout, primarily measure hemispheric or cortical blood flow, whereas TCD studies measure primarily MCA flow velocity, corresponding to cortical blood flow. In healthy individuals, <1.5 MAC sevoflurane anesthesia has no effect on cerebral autoregulation during normocapnia (11). When dynamic autoregulation was studied, where a transient decrease in MAP was induced by a rapid deflation of thigh cuffs previously inflated to above systolic blood pressure for 3 minutes, 1.5 MAC sevoflurane anesthesia slightly impaired autoregulation (12). In contrast, hypercapnia has a profound effect on cerebral autoregulation, and McCulloch et al. (9) reported significant impairment of autoregulation during 0.5 MAC sevoflurane anesthesia when Paco2 exceeded 50 mm Hg. In this study we have chosen an anesthetic regimen known to preserve cerebral autoregulation in cortical blood flow. This allowed us to compare the anterior and posterior circulation under "controlled" and "baseline" conditions. Remifentanil infusion was used as an adjunct to anesthesia in the range of 0.125–0.375 µg ·kg–1 ·min–1, as it had been shown not to affect CBF (13).
Our data documenting preserved autoregulation in MCA during normocapnia under 0.5 MAC of sevoflurane are in agreement with previous studies. Because of methodological limitations, it has been difficult to study the posterior circulation, and little information is available. There is only one published study on autoregulation of the BA, and it is based on TCD (14). Park et al. (14) reported normal dynamic autoregulation of the BA in awake healthy individuals and found it to be of similar magnitude to that of MCA. Although we studied static and not dynamic cerebral autoregulation, our results are consistent with those reported by Park et al. Arguably, one might expect the posterior circulation to have better autoregulatory capacity than the anterior circulation, as some experimental studies have suggested a lower limit of autoregulation with the posterior circulation (15,16). As our present study only examines the autoregulatory capacity within the physiologic range of MAP, we have not excluded a difference in the lower limit of autoregulation between the two circulations.
With regard to CO2R, the BA had been investigated in healthy subjects as well as in patients with neurologic disease (3,15,17–22). The normal values of BA CO2R varies with the studies, depending on patient’s age, methods of testing, depth of BA insonation, and methods of statistical analysis. When TCD methodology was used in healthy awake individuals, CO2R of the BA had been variously shown in several studies to be linear at 2.54 ± 0.4%/mm Hg ETco2 (14), 2.8 ± 0.2%/mm Hg ETco2 (3), and 1.86 ± 1.28%/min of breath hold (17) or exponential with exponent of 0.044 mm Hg–1 (20). Our values of CO2R are higher than these reported studies in conscious individuals, but are consistent with results obtained from patients anesthetized with inhaled anesthetics. The technique of measurement (fixed probe versus hand-held probe) (3,14,18) and depth of insonation (20) could conceivably influence the accuracy of Vba measurement. Contrary to the study by Ogawa et al. (20), who insonated the BA at a depth of 6.5–7.5 cm, we insonated flow velocity of the BA at a depth of 8.5–10 cm, which reflects the proximal BA, and with the TCD probe fixed in the majority of cases. Although most studies showed similarity in CO2R (3,14,20,23), some investigators have reported a difference in CO2R between the anterior and the posterior circulation in healthy awake individuals (4). de Brooder et al. (17), using phase-contrast magnetic resonance imaging, showed an increase of CBF in the BA by 71% secondary to hypercarbia with the breath-holding technique, whereas in internal carotid arteries CBF increased only by 59%–66%, suggesting that the posterior circulation has a higher CO2R than the anterior circulation. Ito et al. (4), measuring CBF using 15O-water and PET at normocapnia, hypocapnia, and hypercapnia in healthy individuals, observed significant hyperperfusion of pons, cerebellum, and thalamus during hypercapnia, again suggesting larger capacitance for vasodilatation compared with anterior and occipital cortices.
If indeed the posterior circulation has a more prominent vasodilating response to an increase in Paco2, this could have clinical significance and may affect the anesthetic management of patients with posterior fossa pathology. Furthermore, inhaled anesthetics may have a different effect on the CBF in the anterior and posterior circulation in humans. For instance, it has been suggested that halothane increases CBF predominantly with anterior rather than with posterior circulation, and isoflurane has the opposite effect (6). Indeed, the difference in MAP responses during retraction in the posterior fossa with different inhaled anesthetics has been attributed to their differential effect on anterior and posterior circulation (7). The extent of volatile anesthetic-induced changes in regional CBF is dependent on the drug dose as well. Kaisti et al. (5), had shown that sevoflurane at 2 MAC in normocapnic patients can increase CBF to the cerebellum but decrease CBF to the forebrain, and this differential effect was not apparent at 1.5 MAC. The interaction between CO2R and inhaled anesthetic dose on anterior-posterior CBF topography in humans is not known. We performed our study under 0.5 MAC of sevoflurane, chosen to have minimal effects on cerebral hemodynamics, and established the fact that under these conditions there is no difference in CO2R and autoregulation between anterior and posterior circulation. Future studies may address the influence of other anesthetics or the dose response.
In conclusion, our study showed that under general anesthesia of 0.5 MAC of sevoflurane and small-dose remifentanil: 1) mean CBF velocities of the BA are less than those of the MCA under all studied conditions: in hypocapnia, normocapnia, and hypercapnia; 2) BA autoregulation is preserved and appears to be similar to that of the MCA; and 3) CO2 vasoreactivity of the BA is similar to that of the MCA. The clinical implication is that during ventilation with a change in CO2 and change in MAP under small-dose sevoflurane anesthesia, the posterior circulation is as equally responsive as the anterior circulation.
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Footnotes |
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