Sevoflurane Increases Lumbar Cerebrospinal Fluid Pressure in Normocapnic Patients Undergoing Transsphenoidal Hypophysectomy 

With approval from our institution's human research committee and written informed consent, we studied 20 patients undergoing transsphenoidal pituitary surgery at the University of California, San Francisco Medical Center. The experimental protocol was identical to one described elsewhere. [2] Briefly, anesthesia was induced with intravenous fentanyl (up to 3 [micro sign]g/kg) and propofol (up to 2.5 mg/kg) and maintained with 70% nitrous oxide in oxygen and an intravenous propofol infusion (100 [micro sign]g [middle dot] kg^-1[middle dot] min^-1). Ventilation was adjusted to maintain end-tidal carbon dioxide pressure between 35 and 40 mmHg. We assigned the patients randomly into two groups. After baseline measurements, patients received either the continuous intravenous propofol maintenance infusion (n = 10) or sevoflurane (n = 10) for 20 min. During the 20-min study period, each patient in the sevoflurane group received, in random order, two concentrations (0.5 times the minimum alveolar concentration [MAC] and 1.0 MAC end-tidal) for 10 min each. MAC for sevoflurane was defined as 1.63 x 10⁰.00269x vol% where x =(40 - age). [3] The transition between test concentrations (0.5 and 1.0 MAC) was achieved by a rapid change of the inspired concentration to the target end-tidal test concentration over 1 min. A fresh gas flow of 10 l/min was used throughout the study to facilitate rapid adjustment of the end-tidal anesthetic concentration.

Lumbar cerebrospinal fluid (CSF) pressure was measured via an intrathecal catheter; arterial blood pressure via a radial arterial cannula; and heart rate via three-lead electrocardiography. The transducers were zeroed at the level of the midcranium. Anesthetic concentration was measured continuously using an infrared anesthetic gas monitor (Datex Ultima, Datex-Ohmeda, Helsinki, Finland). Hemodynamic, lumbar CSF pressure, and anesthetic gas data were recorded at 10-s intervals from the monitors through an automated data acquisition system. Blood pressure was maintained within +/- 20% of baseline value throughout the study by administration of phenylephrine as necessary.

For analysis, the blood pressure, heart rate, and lumbar CSF pressure data (recorded every 10 s) were reduced to 1-min median values. Cerebral perfusion pressure was calculated as mean arterial pressure minus lumbar CSF pressure. For continuously measured variables (systolic blood pressure, heart rate, lumbar CSF pressure and cerebral perfusion pressure), baseline values were defined as the median values obtained over 1 min before the 20-min study period. The peak, lowest, and 10-min values were calculated for each study period for 0.5 and 1.0 MAC.

Demographic data were analyzed using a t test. Values for peak and lowest systolic blood pressure, heart rate, lumbar CSF pressure, and cerebral perfusion pressure after each change in anesthetic concentration and the last values obtained during each 10-min study interval were compared with baseline values in each group using repeated-measures analysis of variance followed by Dunnett post hoc testing, and between the study and propofol groups using a t test on change from baseline values. Carbon dioxide data were compared using repeated-measures analysis of variance. Data are reported as the mean +/- SD. P < 0.05 identified statistical significance.

The study groups did not differ demographically (age, weight, height), nor in the dosage of fentanyl or propofol required for induction. End-tidal carbon dioxide pressure was maintained stable in each patient throughout study, and there was no difference between groups in these values. Sevoflurane concentrations ranged, depending on subjects' ages, from 0.82–0.99 vol% and 1.63–1.99 vol% for the 0.5 and 1.0 MAC targets, respectively. Target anesthetic agent concentrations were achieved within 1 min from the time the concentration was changed.

Lumbar CSF pressure, cerebral perfusion pressure, and hemodynamic data are shown in Table 1. Lumbar CSF pressure increased and cerebral perfusion pressure decreased significantly with both 0.5 and 1.0 MAC sevoflurane compared with the propofol group. Systolic blood pressure decreased with both concentrations of sevoflurane, but not in the propofol group. Phenylephrine was administered to five patients in the sevoflurane group (range, 50–300 [micro sign]g), but none in the propofol group.

Our results demonstrate that lumbar CSF pressure increases slightly with both 0.5 and 1.0 MAC concentrations of sevoflurane in unstimulated normocapnic patients undergoing transsphenoidal hypophysectomy. In contrast, lumbar CSF pressure remained stable during continuous propofol anesthesia.

The existing data on the effects of sevoflurane on ICP in neurosurgical patients are limited. Artru et al. studied three concentrations (0.5, 1.0, and 1.5 MAC) of sevoflurane and isoflurane in normocapnic neurosurgical patients, and reported that neither anesthetic agent altered ICP. [4] In contrast we found that both 0.5 and 1.0 MAC sevoflurane caused a statistically significant, although clinically irrelevant, increase in lumbar CSF pressure in normocapnic neurosurgical patients. The differences in these findings may be explained in part by differences in study designs. Artru et al. [4] compared ICP values during sevoflurane administration without concomitant use of nitrous oxide to control values that were obtained during administration of 50–70% N²O. Therefore, considering that N²O increases ICP, [5] another interpretation of their results might be that 50–70% N²O and 0.5–1.5 MAC sevoflurane have similar effects on ICP. This may further explain why they also found that isoflurane had no effect on ICP.

Several studies in animals have examined the effects of sevoflurane on ICP. [6–9] Consistent with our results, sevoflurane has been reported to increase ICP in rabbits and cats. [6–8] In contrast to our results, Takahashi et al. [9] found that sevoflurane did not have an effect on ICP in dogs. In their study ICP changed from 3.8 +/- 0.7 mmHg (mean +/- SEM) in hypocapnic dogs without sevoflurane to 6.4 +/- 1.4 mmHg in hypocapnic dogs with 1.5 MAC sevoflurane. However, their finding of no change in ICP may be explained in part by their analysis that compared ICP values during sevoflurane anesthesia in hyperventilated dogs with normocapnic baseline values.

All commonly used volatile anesthetics appear to increase ICP. We recently reported that both 0.5 and 1.0 MAC desflurane and isoflurane increased lumbar CSF pressure in a study identical to the present study in design and patient population. [2] In comparison to the statistically significant but clinically insignificant 2 +/- 2 mmHg increase in lumbar CSF pressure found in the present study with 1 MAC sevoflurane, we previously found that lumbar CSF pressure increased by 5 +/- 3 and 4 +/- 2 mmHg with 1 MAC desflurane and isoflurane, respectively. Analyzing the pooled data from these two studies revealed that the increases in lumbar CSF pressure did not differ between the three inhalation anesthesia groups (P = 0.179 for 0.5 MAC and P = 0.097 for 1.0 MAC; analysis of variance;Figure 1).

The authors thank Charles Wilson, M.D., for his support, and the patients for volunteering their time.