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NEUROSURGICAL ANESTHESIA

A Comparison of Three Anesthetic Techniques in Patients Undergoing Craniotomy for Supratentorial Intracranial Surgery

Department of Anesthesia and Perioperative Medicine, University of California, San Francisco, California

Address correspondence and reprint requests to Dr. Pekka Talke, Department of Anesthesia and Perioperative Medicine, University of California, San Francisco, CA 94143-0648. Address e-mail to talkep{at}anesthesia.ucsf.edu

	Abstract

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Several anesthetic techniques have been used successfully to provide anesthesia for resection of intracranial supratentorial mass lesions. One technique used to enhance recovery involves changing anesthesia from vapor-based to propofol-based for cranial closure. However, there are no data to support a beneficial effect of this approach in the immediate postoperative period after craniotomy. We evaluated 3 anesthetic techniques in 60 patients undergoing elective surgery for supratentorial mass lesions. Patients were randomly assigned to three anesthesia study groups: propofol infusion, isoflurane inhalation, and these two techniques combined. In the combination group, once the dura was closed, isoflurane was discontinued and propofol infusion simultaneously started. We studied intra- and postoperative hemodynamics and several recovery variables for 2 h after the end of anesthesia. Baseline and average intraoperative blood pressure and heart rate values did not differ among the groups. Heart rate and blood pressure increased similarly in all groups in response to intubation and pin placement and postoperatively. None of the recovery event times (open eyes, extubation, follow commands, oriented, Aldrete score) or psychomotor test performance differed significantly. We conclude that the sequential administration of isoflurane and propofol did not provide earlier recovery and cognition than the intraoperative use of isoflurane alone.

IMPLICATIONS: We evaluated three anesthetic techniques with and without propofol in patients undergoing elective surgery for supratentorial mass lesions by using a prospective, randomized clinical study design and found that the three anesthetics did not differ in intra- or postoperative hemodynamic stability or early postoperative recovery variables.

	Introduction

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Several anesthetic techniques have been used successfully to provide anesthesia for resection of intracranial supratentorial mass lesions (1–4). The optimal technique should not increase intracranial pressure and should provide intra- and postoperative hemodynamic stability, as well as rapid and safe awakening that will allow neurologic evaluation soon after surgery. One technique used to enhance recovery involves changing anesthesia from vapor-based to propofol-based for cranial closure, the final portion of the procedure lasting approximately 1 h. However, there are no data to support a beneficial effect of this approach in the immediate postoperative period after craniotomy, and there may be cost implications. To test our hypothesis that changing anesthesia from vapor-based to propofol-based for cranial closure would result in more rapid recovery (time to follow commands), we evaluated three anesthetic techniques with and without propofol in patients undergoing elective surgery for supratentorial mass lesions using a prospective, randomized clinical study design.

	Methods

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With approval from our human research committee and written informed consent, we studied 60 patients undergoing elective surgery for supratentorial mass lesions. Entry criteria were defined as patients who were >18 yr of age, ASA physical status II, III, or IV, and scheduled for elective supratentorial neurosurgical procedure. Excluded from study were patients with clinical evidence of increased intracranial pressure, and those scheduled for an emergency surgery. Patients were randomly assigned to one of three study groups by sealed, numbered envelopes.

Experimental Protocol
At least 1 day before surgery, all patients had a routine preoperative history assessment and physical examination. On the morning of surgery, patients were premedicated with midazolam 1–2 mg IV. After entry into the operating room, patients then breathed 100% oxygen while anesthesia was induced IV with 3 µg/kg fentanyl and either propofol (Gencia Sicor Pharmaceutical Inc., Irvine, CA) or thiopental. A muscle relaxant of the anesthesiologist’s choice was administered to achieve muscle relaxation before tracheal intubation, along with an additional 2 µg/kg fentanyl. After intubation, an esophageal temperature probe and a Foley urinary catheter were placed. Anesthesia was then maintained with 70% nitrous oxide in oxygen, a 2 µg · kg^-1 · h^-1 fentanyl infusion, and either propofol or isoflurane (as described below). Muscle relaxation was maintained as necessary at the discretion of the anesthesiologist. The management of ventilation and end-tidal carbon dioxide was left to the discretion of the anesthesiologist. Fentanyl infusion was discontinued once the bone flap was secured. Residual neuromuscular block was reversed by using neostigmine and glycopyrrolate when appropriate. Nitrous oxide was discontinued at the end of surgery and this action was defined as the end of anesthesia time.

Monitoring included a noninvasive blood pressure cuff, electrocardiograph, and a pulse oximeter. Blood pressure also was monitored by using a radial artery cannula placed either before or after the induction of anesthesia, before tracheal intubation. Baseline heart rate and blood pressure (noninvasive or invasive) were measured after premedication, before the induction of anesthesia while patients lay supine on the operating room table. Intraoperative temperature control was left to the discretion of the anesthesiologist.

Anesthetic Technique
There were three anesthesia study groups: propofol infusion (PRO, n = 20), isoflurane inhalation (ISO, n = 20), and these two techniques combined (ISO/PRO, n = 20). In all groups, the anesthetic concentration was varied at the discretion of the anesthesiologist to achieve the smallest concentration possible to maintain hemodynamic variables within predetermined limits (see below). Also, the administration of anesthesia (with the exception of nitrous oxide) was discontinued at approximately 10 min before the end of surgery.

Anesthesia in the PRO group was induced with up to 3 mg/kg propofol and maintained with an infusion of 50–200 µg · kg^-1 · min^-1. In the ISO group, induction was achieved with up to 5 mg/kg thiopental and anesthesia maintained with up to 0.55 vol% end-tidal concentration of isoflurane. For the combined group (ISO/PRO), anesthesia was induced with up to 3 mg/kg propofol and maintained with up to 0.55 vol% end-tidal isoflurane. Once the dura was closed, isoflurane was discontinued and propofol infusion (50–200 µg · kg^-1 · min^-1) simultaneously started. A fresh gas flow of 3 L/min was used to facilitate the elimination of isoflurane. Propofol infusion was discontinued an estimated 10 min before the end of surgery (removal of pins).

Hemodynamic Management
Intraoperatively, systolic blood pressure and heart rate were maintained within predetermined limits. Bradycardia was defined as heart rate <40 bpm, tachycardia as heart rate >100 bpm, hypertension as a >30% increase in systolic blood pressure, and hypotension as a >30% decrease in systolic blood pressure (with a lower limit of 90 mm Hg) from preoperative baseline values.

After establishing an adequate level of anesthesia with either isoflurane or propofol, bradycardia was treated by the administration of glycopyrrolate, and tachycardia and/or hypertension by first increasing the expired isoflurane concentration up to 0.55 vol% or the rate of propofol infusion up to 200 µg · kg^-1 · min^-1. If hypertension or tachycardia persisted, labetalol was administered. Hypotension was first treated by decreasing the inspired isoflurane concentration or the rate of propofol infusion and, if persistent, by the administration of phenylephrine or ephedrine. Postoperative hemodynamic management was left to the discretion of the physician caring for the patient.

Clinical Data Collection
Arterial blood pressure (systolic, diastolic, and mean) and heart rate were measured continuously (Propaq 106; Protocol Systems, Beaverton, OR), from before the induction of anesthesia until 2 h after the end of surgery. Arterial blood pressure was measured via a radial artery cannula connected to a Transpac II transducer (Abbott Laboratories, North Chicago, IL). Hemoglobin oxygen saturation was measured by using a pulse oximeter incorporated into the Propaq 106. End-tidal concentrations of anesthetic vapor, nitrous oxide, oxygen, and carbon dioxide were measured continuously by using an infrared anesthetic gas monitor (Datex Ultima; Datex Instrumentarium, Helsinki, Finland). Hemodynamic, SpO₂, and anesthetic gas data were recorded at 10-s intervals from the monitors through an automated data acquisition system. Esophageal temperature was recorded at the end of the operation before tracheal extubation.

Recovery Measurements
Patient recovery was studied for 2 h after the end of anesthesia, as defined by the discontinuation of nitrous oxide. Because most postoperative hemodynamic changes occur during emergence from anesthesia, we also analyzed hemodynamic changes during the first 30 min after the end of anesthesia, defining this period as early recovery. Once nitrous oxide was discontinued, we recorded the time required for patients to: 1) open their eyes, 2) follow simple commands ("squeeze my hand"), 3) be extubated, and, 4) orient to time and place. The rate of recovery was evaluated by using a modified Aldrete score every 15 min from the end of anesthesia until the patient obtained at least 10 of the 12 potential points (5). The visual analog scale was used to determine sedation (0 = completely awake to100 = cannot stay awake), pain (0 = no pain to 100 = most pain I have ever felt), and nausea (0 = no nausea to 100 = as nauseous as I have ever been) during recovery. Sedation also was monitored by one of the investigators before anesthesia and at 30, 60, 90, and 120 min after the end of anesthesia by using the Ramsey scoring system (6); the same investigator monitored nausea (retching) and vomiting by observation at the same postoperative intervals. Patients completed the digital symbol substitution and P-deletion tests before premedication (baseline) and at 60 and 120 min after the end of anesthesia (7,8).

To assess the difference in cost for the three anesthetic techniques, we calculated the expense of the variable component of anesthesia (propofol, isoflurane, thiopental) for each group by using acquisition costs of $17.95/500 mg for propofol, $17/100 mL for isoflurane, and $5.50/500 mg for thiopental.

The duration of anesthesia was defined as the time from the induction of anesthesia to the discontinuation of nitrous oxide. The duration of surgery was defined as the time from skin incision to last suture. Before analysis, continuously monitored hemodynamic and anesthetic gas data were reduced to 1-min median values. Area under the curve was used to quantify the incidence and severity of hemodynamic aberration, and was calculated as the sum of the amount heart rate or systolic blood pressure exceeded the predetermined limits for each 1-min epoch. Continuous data were analyzed by using repeated-measures analysis of variance. Nonparametric data were analyzed by using the Kruskal-Wallis test. Categorical data were analyzed by using the ² test. Data were expressed as mean ± SD. P < 0.05 indicated statistical significance.

	Results

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There were no significant differences in age, weight, sex, ASA class, duration of surgery, duration of anesthesia, or time from beginning of dural closure to the end of anesthesia among the anesthetic groups. The mean ages in the PRO, ISO, and ISO/PRO groups were 49 ± 14, 44 ± 15, and 46 ± 13 yrs, respectively; mean weight was 81 ± 21, 73 ± 19, and 78 ± 22 kg; mean duration of surgery, 286 ± 97, 279 ± 89, and 306 ± 108 min; mean duration of anesthesia, 389 ± 85, 372 ± 98, and 389 ± 121 min; and mean duration from the beginning of dural closure to the end of anesthesia, 86 ± 29, 86 ± 15, and 80 ± 23 min. The patients consisted of 29 men and 31 women. Of the 60 operations, 55 were for resection of an intracranial tumor (n = 18, 19, and 18, respectively, for the PRO, ISO, and ISO/PRO groups), 4 for resection of an intracranial arteriovenous malformation (n = 1, 1, and 2), and 1 for resection of an intracranial cyst (PRO group).

Baseline and average intraoperative blood pressure and heart rate values did not differ among the groups. Heart rate and blood pressure responses immediately before and for the first 10 min after tracheal intubation and pin insertion are illustrated in Figures 1 and 2, respectively. Heart rate and blood pressure increased similarly in all groups in response to intubation and pin placement.

View larger version (32K): [in this window] [in a new window]   Figure 1. Heart rate (left panels) and systolic blood pressure (right panels) values for 5 min before, and 10 min after, the end of endotracheal intubation (arrow) for each of the three study groups. Data are mean (thick line) and SD (thin lines) of hemodynamic values, which were recorded electronically every 10 s.

View larger version (31K): [in this window] [in a new window]   Figure 2. Heart rate (left panels) and systolic blood pressure (right panels) values for 5 min before, and 10 min after, the end of placing the head in Mayfield pins (arrow) for each of the three study groups. Data are mean (thick line) and SD (thin lines) of hemodynamic values, which were recorded electronically every 10 s.

Mannitol was administered to 13, 11, and 11 patients in the ISO, PRO, and ISO/PRO groups, respectively (P = NS). Intraoperatively administered crystalloid volume was 2158 ± 995, 2526 ± 1288, and 2018 ± 742 mL; intraoperative urine output was 1693 ± 721, 1964 ± 672, and 1539 ± 703 mL; and estimated blood loss was 258 ± 118, 289 ± 251, and 362 ± 217 mL for the ISO, PRO, and ISO/PRO groups, respectively (P > 0.05 for all).

Increases in blood pressure and heart rate during early recovery (first 30 min) did not differ for the 3 anesthetic techniques (Fig. 3). Average, minimal, and maximal heart rate and systolic blood pressure values and the amount of bradycardia, tachycardia, hypotension, and hypertension, as defined by the protocol, for the 2-h recovery period, also did not differ (Table 2). To control postoperative blood pressure, one patient in each group received labetalol, one in the PRO group received phenylephrine, and one each in the PRO and ISO/PRO groups received hydralazine.

View larger version (35K): [in this window] [in a new window]   Figure 3. Heart rate (left panels) and systolic blood pressure (right panels) values for the first 30 min after the end of anesthesia for each of the three study groups. Data are mean (thick line) and SD (thin lines) of hemodynamic values, which were recorded electronically every 10 s.

View larger version (28K): [in this window] [in a new window]   Figure 4. Time from the end of anesthesia until opening eyes (left top), until extubation (bottom left), until following commands (top right), and until being oriented to time and place (bottom right) for a cumulative number of patients in each group. Thin line = isoflurane group, thick line = propofol group, dotted line = isoflurane/propofol group. Missing values are a result of patients not reaching the end-point within 2 h from anesthesia.

Neither the Ramsey sedation scores nor the patient-recorded visual analog scale scores for sedation, pain, or nausea differed significantly by anesthetic technique. Medication for postoperative pain was required in 13, 16, and 14 patients, respectively, in groups ISO, PRO, and ISO/PRO (P = 0.6).

Drug costs were $16.62 ± 3.88, $113.83 ± 40.51, and $30.78 ± 10.94 for groups ISO, PRO, and ISO/PRO, respectively (P < 0.0001; PRO versus ISO and ISO/PRO).

	Discussion

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We conducted this study to investigate whether the duration of recovery immediately after craniotomy could be improved by substitution of propofol for isoflurane anesthesia before cranial closure. Theoretically, discontinuing a potentially slowly eliminated anesthetic (isoflurane) earlier than usual before the end of anesthesia to substitute one having a short context-sensitive half-life should improve early patient recovery. However, we found that this approach offered no significant clinical benefit relative to isoflurane anesthesia alone. The only significant difference for the three anesthetic techniques was cost.

Our results are similar to those of other investigators who have reported relatively short recovery times after craniotomy using different combinations of drugs, all at relatively small doses (1,3,4,9). Reported median times to opening eyes, tracheal extubation, following commands, and orientation to time and place have been approximately 3, 5, 5, and 10 minutes, respectively, compared with our own of 3, 4, 4, and 13 minutes for all 60 patients (1,2). These data suggest that any clinically significant reduction in early recovery time from anesthesia is unlikely.

In contrast to the studies just mentioned, anesthetic techniques requiring large time-averaged end-tidal isoflurane concentrations (>0.5 vol%) have consistently demonstrated prolonged recovery from anesthesia (9–11). Exclusive of using large doses of isoflurane, only a few other studies of supratentorial craniotomies have found one anesthetic technique to provide a faster emergence and recovery from anesthesia than another (9–11). However, in most of these studies, the prolonged postoperative recovery seems to be a reflection of the protocol design, such as use of unusually large or fixed anesthetic drug doses, or discontinuation of anesthetics too late to allow early recovery (9–11). We attempted to design the anesthesia protocols so that they would not bias results toward any one technique and would simulate the clinical use of the anesthetics as much as possible whereas still allowing meaningful comparisons. To achieve this, we chose to maintain constant narcotic and nitrous oxide doses in each group, and to allow titration of only propofol and isoflurane to clinical end-points.

Our psychomotor function testing results (digital symbol substitution and P-deletion test) were disappointing. We included these tests to evaluate potential differences in the speed of cognitive recovery from the different anesthetics. Surprisingly, only about half of the patients in each group were able to complete these tests even when their Ramsey scores did not differ significantly from baseline, suggesting neurologic causes for the poor psychomotor function testing performance.

A modified Aldrete score has been used to assess the speed of early postoperative recovery and readiness for discharge from the postoperative care unit (5). Similar to Todd et al. (1), who also compared three different anesthetic techniques in patients with supratentorial craniotomies, we found that most of our patients achieved an Aldrete score of 9 or more within 15 minutes from the end of anesthesia.

Our continuous hemodynamic monitoring method allowed us to identify and quantify all episodes of hypertension, hypotension, bradycardia, and tachycardia. Our data demonstrate that all three anesthetic techniques provide similar, acceptable intraoperative hemodynamic control, with minimal hyperdynamic responses to stimulating events. However, the incidence of postoperative hypertension and tachycardia in all groups was surprisingly frequent (>50%) (Table 2). These data suggest that the postoperative course of our patients could be improved by the prophylactic administration of antihypertensive medications before emergence from anesthesia and/or by more rigorous postoperative hemodynamic control.

Based on previously published data, we assumed that the average time to orient to time and place postoperatively would be 10 minutes (1). We then calculated that, to have 80% power to detect (P < 0.05), a 50% reduction in time to orient to time and place would require 20 patients per group, resulting in our study population of 60. Nonetheless, we did not have enough power to detect significant differences for all of the variables analyzed. Despite this limitation, our data suggest that the ISO/PRO technique did not even show trends toward providing better early postoperative recovery than the propofol or isoflurane techniques alone.

Our study is limited by not evaluating the effect of our anesthetics on intracranial pressure. Our study also is limited by not evaluating short- and long-term outcome for our patients. We did not include these end-points because our power to draw definite conclusions on outcomes would have been too limited. Finally, our study protocol did not include double-blinding for reasons reviewed previously in similar studies (1). We minimized potential bias by using computer-assisted data collection with concrete end-points at frequent intervals (such as eye opening), and standardized tests.

We conclude that any of the three anesthetic techniques we studied are acceptable for elective supratentorial intracranial surgeries. Our data suggest that all three approaches provide an early recovery comparable to or better than that resulting from previously studied techniques in similar patient populations. Our findings do not support our hypothesis that discontinuing the (relatively) slowly eliminated isoflurane before cranial closure to substitute the rapidly eliminated propofol to complete surgery would improve the rate and quality of early recovery. The sequential administration of isoflurane and propofol did not provide earlier recovery and cognition than the intraoperative use of isoflurane alone. The primary difference among our three techniques was cost.

	Acknowledgments

 
Supported by departmental and university funds.

We thank Winifred von Ehrenburg, PhD, for her editorial assistance, and the patients for volunteering their time.

	References

Top Abstract Introduction Methods Results Discussion References

 

1. Todd MM, Warner DS, Sokoll MD, et al. A prospective, comparative trial of three anesthetics for elective supratentorial craniotomy: propofol/fentanyl, isoflurane/nitrous oxide, and fentanyl/nitrous oxide. Anesthesiology 1993; 78: 1005–20.[Web of Science][Medline]
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9. Van Hemelrijck J, Van Aken H, Merckx L, Mulier J. Anesthesia for craniotomy: total intravenous anesthesia with propofol and alfentanil compared to anesthesia with thiopental sodium, isoflurane, fentanyl, and nitrous oxide. J Clin Anesth 1991; 3: 131–6.[Medline]
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