Desflurane is a volatile anesthetic with low blood solubility, which allows for early recovery after anesthesia. Its use in neurosurgery may be attractive because it facilitates postoperative early neurological patient evaluation.1,2 The use of desflurane in neurosurgery has been debated because of its capacity to promote cerebral vasodilatation, as demonstrated both in animals and human studies.3–5 However, no variation in intracranial pressure (ICP) in normocapnic patients undergoing removal of supratentorial tumors using desflurane anesthesia was demonstrated in one clinical study.6 Even though desflurane and sevoflurane are widely used in clinical practice, there are no large studies directly comparing these drugs in patients undergoing neurosurgical resection of supratentorial tumors. The aim of this prospective, randomized, open-label, clinical trial was to compare sevoflurane and desflurane anesthesia in patients undergoing supratentorial intracranial surgery. The primary end-point was the comparison of early postoperative recovery and cognitive function within the two groups; we also evaluated brain relaxation, hemodynamic events, vomiting, shivering, pain, and respiratory complications.
Between April 2005 and February 2006, 120 patients (66 men), ASA physical status I–III, aged 19–76 yr, Glasgow Coma Scale 15, undergoing craniotomy for supratentorial expanding lesions, were enrolled in this study after written, informed consent and approval by our local ethical committee. The criteria of exclusion were pregnancy, known allergies to any anesthetic drug, Glasgow Coma Scale <15, obesity (body mass index >30), history of drug or alcohol abuse, and/or refusal to sign consent. All patients had radiological evidence of mass effect (any degree of midline shift or any evidence of cerebral edema). All patients received dexamethasone 10 mg IV 1 h before induction of anesthesia. The patients were randomly allocated using a computer-generated randomization scheme into two groups: in Group S (60 patients, 52 ± 16 yr) anesthesia was maintained using sevoflurane, whereas in Group D (60 patients, 60 ± 14 yr) anesthesia was maintained using desflurane. In the preoperative area, patients completed a baseline Visual Analog Scale (VAS), with 0 mm = no pain or nausea and 100 mm = worst possible pain or nausea.7 An isotonic crystalloid saline solution (10 mL/kg, preoperatively) was infused through a peripheral IV catheter, and a second catheter was inserted for drug administration. Arterial blood pressure was measured via a radial artery cannula connected to a transducer (Hemomed, Siemens) positioned before surgery, after sedation with midazolam (0.03 mg/kg IV) and local infiltration with lidocaine. All patients were administered oxygen for 3 min, and a closed CO2 absorber circuit with a 5 L reservoir bag was used. In all patients, anesthesia was induced with propofol (3 mg/kg), fentanyl (3 μg/kg), and vecuronium (0.1 mg/kg) with the patient breathing 100% O2. After intubation of the trachea, mechanical ventilation was begun. An inspired mixture of air and oxygen (2:1) was administered. Ventilation was adjusted to achieve a Paco2 of 35 mm Hg. The inhaled anesthetic concentration was age adjusted to obtain approximately 1.2 minimum alveolar anesthetic concentration (MAC). MAC range for sevoflurane and desflurane was 0.8–1.5. The end-tidal concentrations of the volatile anesthetics and the ETco2 were monitored continuously. Throughout the study period, MAC was recorded in real-time for MAC-hour calculation (average MAC length of exposure).
Vecuronium was administered as the neuromuscular blocking drug according to train-of-four monitoring. Body temperature was monitored using a bladder catheter and maintained between 35°C and 36°C with a convective device blanket. Infiltration of the scalp with bupivacaine 0.25% was accomplished in all patients before incision of the skin. At dural opening, brain relaxation was assessed by the attending neurosurgeon, who was blinded to the study group, by using a 4-point scale: 1, relaxed brain; 2, mild brain swelling, acceptable; 3, moderate brain swelling, no treatment required; and 4, severe swelling, treatment required.
Sevoflurane and desflurane were reduced after the bone flap was secured and stopped after skin dressing.
At the end of surgery, all patients received ketorolac 30 mg and labetalol 100 mg IV (in fractional doses) after the anesthetics were discontinued and received supplemental oxygen at a flow rate of 8 L/min (fraction of inspired oxygen 40%) during the entire period of observation.
Intraoperatively, mean arterial blood pressure (MAP) and heart rate (HR) were maintained within predetermined limits: desflurane and sevoflurane doses were adjusted to maintain the MAP within a range of 20% of preanesthesia level with HR <90 bpm. MAP more than 20% above baseline, HR responses more than 90 bpm, swelling, or movement were used during maintenance anesthesia to justify an increase in drug administration. Additional boluses of fentanyl 0.7 μg/kg were given if the patient failed to respond to increases in the level of the primary anesthetic (sevoflurane or desflurane). If relative hypertension (MAP above 30% of baseline value) persisted despite achievement of maximal allowed anesthetic concentration, episodes of relative hypertension or tachycardia (lasting more than 1 min) were treated with labetalol (25 mg bolus). Anesthetics were decreased only in response to a reduction of MAP of 20% of preinduction values that was not responsive to replacement of intraoperative fluid losses. When clinically indicated, a vasopressor (ephedrine 5 mg IV) was administered. The incidence of episodes of hypotension (MAP decrease below 70% of the baseline value for more than 1 min), hypertension (MAP increase above 130% of the baseline value for more than 1 min), bradycardia (HR <50 bpm for more than 1 min), and tachycardia (HR >90 bpm for more than 1 min) was recorded and treated.
Pao2 and Paco2 were monitored during surgery and for 3 h after tracheal extubation. Blood samples for gas analysis (i-stat Abbott gas analyzer) were taken every hour during surgery, every 15 min after extubation for the first hour, and every hour for the following 2 h.
Emergence time was measured as the time between anesthetic discontinuation and the time at which patients opened their eyes (spontaneously or on verbal prompting repeated every 2 min). Tracheal extubation time was measured as the time elapsing from anesthetic discontinuation and extubation (performed when the patient obeyed verbal commands and adequate spontaneous ventilation [tidal volume 4 mL/kg]) was established. Recovery time was measured as the time elapsing from discontinuation of anesthetics and the time when patients were able to recall their names and dates of birth (on verbal prompting every 2 min after extubation).
Cognitive behavior was evaluated with the Short Orientation Memory Concentration Test (SOMCT)8 by an experienced physician blinded to the anesthetic strategy. SOMCT requires subjects to recall the current year and month, the details of a short story, and to repeat in numerical order and reverse order the sequence of the months of the year. These five questions yielded scores ranging from 0 to 28, with higher scores indicating better function and scores more than 20 were considered normal. The SOMCT score was evaluated before surgery and every 15 min after extubation for the first hour and every hour for the following 2 h.
In the postanesthesia care unit, a blinded observer monitored the patients for 3 h: the patient’s neurological status (evaluation of level of consciousness, presence of new motor or sensory deficit, and presence of brain stem reflexes) was tested every 15 min; the manifestation of shivering, postoperative nausea and vomiting and the request for analgesic medications, the incidence of hypotension, hypertension, tachycardia and bradycardia, and respiratory complications were identified and treated. Blood samples for gas analysis (i-stat Abbott gas analyzer) were taken every 15 min after extubation for the first hour and every hour for the following 2 h. Respiratory complication was defined as Pao2 below 90 mm Hg (flow rate of 8 L/min, fraction of inspired oxygen 40% during the entire period of observation), and Pco2 more than 45 or need for reintubation. Pain and nausea requiring rescue medication (Visual Analog Scale above 50) were treated with ketorolac 30 mg IV and metoclopramide 10 mg IV, respectively. Shivering was treated with nefopam 10 mg IV.9
Episodes of hypotension, hypertension, bradycardia, and tachycardia were recorded and treated.
The study was powered to detect a difference in emergence time of at least 5 min between the two groups, assuming emergence time in Group S as 15 ± 8 min (requiring at least 54 patients per group). This sample size was also adequate to detect small differences in cognitive function (i.e., the sample size required to detect a 10% difference in postoperative SOMCT was 20 patients per group). Data are expressed as mean ± sd (for continuous variables) or as percentages (for proportions). Continuous variables were compared by unpaired two-tailed Student’s t-test or by repeated measures analysis of variance followed, whenever appropriate, by Bonferroni post hoc test. Proportions expressing the incidence, in each study group, of events during and after surgery were compared by the χ2 statistics. A P value <0.05 was considered statistically significant.
From 129 eligible patients, 9 subjects (6 in Group S and 3 in Group D), in whom early awakening was not considered safe (site of surgery, predictable prolonged intervention, or predictable blood losses), were excluded. The analysis was therefore performed on 120 patients.
Baseline characteristics and demographic data, including, sex and ASA status were similar in the two treatment groups except for MAC-hours result (Table 1).
In 13 patients (6 in Group S and 7 in Group D; P = 0.77) intracranial volume was graded as severely abnormal at dural opening (Grade 4) and decompression therapy was necessary to decrease brain bulking.
The mean emergence time was similar between the two groups, whereas the mean tracheal extubation time and recovery time were longer in the Group S (Table 2). The SOMCT score differed between the two groups only at the earliest assessment, 15 min after extubation (Table 3).
Paco2 increase above 45 mm Hg was present in 33% of patients (40% in Group S and 27% in Group D; P = 0.12) immediately after extubation. After the first hour, a Paco2 value above 45 mm Hg was encountered in 18% of patients (17% in Group S and 20% in Group D; P = 0.64) (Table 4). Pao2 values were below 90 mm Hg in six patients (four in Group S and two in Group D; P = 0.34). In two of six patients (both in Group S), reintubation was necessary because of a persistent epileptic crisis.
We recorded 4 intraoperative hypotensive events (3 in Group S and 1 in Group D; P = 0.30), 10 intraoperative hypertensive episodes (6 in Group S and 4 in Group D; P = 0.30). Postoperatively, we did not observe any hypotensive episodes, whereas hypertensive episodes were present in 10 of 60 patients in Group S (17%) and in 12 of 60 patients in Group D (20%) (P = 0.64).
Bradycardia was found in 6 of 60 patients (10%) in Group S vs 5 of 60 patients (8%) in Group D (P = 0.75); tachycardia was present in 7 of 60 patients (12%) in Group S vs 11 of 60 patients (18%) in Group D (P = 0.30).
Shivering was present in 7 patients in Group S (12%) and 10 patients in Group D (17%) (P = 0.43). Pain episodes requiring treatment were reported in 13 patients in Group S (22%) and in 10 patients in Group D (17%) (P = 0.48). Postoperative nausea and vomiting episodes requiring rescue medication were recorded in seven patients in Group S (12%) and in eight patients in Group D (13%) (P = 0.78).
We did not observe any neurologic complications in either group.
Our study shows that maintenance of anesthesia with desflurane resulted in a faster recovery compared with sevoflurane; in the desflurane group, the time to extubation was approximately 2 min shorter and the recovery time 6 min shorter. Such a difference might not be an important gain in the general population of surgical patients, but in neurosurgical patients it might help distinguish which patient has a new neurological deficit and would therefore require a specialized diagnostic test or even emergent reintervention. Although we believe that the clinical and practical implications of these findings may not be crucial, we highlight that the faster recovery obtained with desflurane can be achieved with no adverse effects. This finding may be helpful for anesthesiologists in the decision whether to use desflurane in neurosurgical patients with no clinical signs of intracranial hypertension.
Moreover, postoperative recovery of cognitive function was comparable between desflurane and sevoflurane anesthesia except for the evaluation obtained 15 min after tracheal extubation, when the SOMCT score was statistically different between the two groups, suggesting a faster recovery in the desflurane group. The SOMCT score in the two groups were similar at 30 min after tracheal extubation and remained comparable over the next 2 h. Although rapid recovery of activities requiring coordination and cognitive functions are among the most desirable goals in neurosurgical patients, we believe that the impact on clinical practice of this finding is marginal. In fact, the mean SOMCT in the two groups was above the value considered normal (score >20) and equivalence between the two groups was obtained at 30 min after extubation. A 15 min difference in recovery of almost complete cognitive capacity would not be crucial in modifying medical strategies, such as requiring a specialized diagnostic test or even an emergent reintervention.
Prospective studies comparing sevoflurane and desflurane in neurosurgical patients are scarce. Kaye et al.6 reported a 50% reduction in the time to eye opening and obeying commands in neurosurgical patients anesthetized with desflurane compared with those who received isoflurane. The result of Kaye et al. was not conclusive because the study was not powered to address this specific issue but, interestingly, the time to obey commands in their study was longer (mean 30 min) than in our study (mean 15 min). Dissimilar anesthetic protocols, including midazolam and fentanyl infusions used in the protocol of Kaye et al., may explain differences in recovery time between the two studies.
Other studies in nonneurosurgical patients have also found a faster recovery with desflurane anesthesia compared with sevoflurane, even after adjusting for gender, age, and type of surgery.10–12 Our study confirms a faster recovery with desflurane compared with sevoflurane in neurosurgical patients undergoing resection for supratentorial tumors. A potential confound in our study is the small but significant difference in MAC hours between the two groups, which may be the result of slight differences in surgery duration. However, we think that the faster recovery was related to desflurane’s lower drug solubility producing a more rapid recovery.1,2 Furthermore, a comparable depth of anesthesia between the two groups was assured by the age-adjusted MAC of 1.2 used in each patient and by accurate and standardized clinical monitoring of depth of anesthesia.
The advantages of rapid recovery from desflurane anesthesia may be tempered by the effects of desflurane on cerebral perfusion pressure and ICP.2 Previous studies, including our own, reported less cerebral swelling after dural opening in patients anesthetized with propofol compared with patients anesthetized with either isoflurane or sevoflurane.13,14 We therefore wanted to evaluate the effect of desflurane anesthesia on intracranial volume as assessed by the operating surgeon. In 13 patients (11%, 6 sevoflurane and 7 desflurane), intracranial volume was graded as severely abnormal at dural opening and therapy was necessary to decrease severe brain swelling. Although our study was not powered to detect differences in brain relaxation between the two anesthetic strategies, our finding is consistent with the findings of Todd et al.,15 who described a 10% incidence of brain swelling in patients undergoing neurosurgical resection of tumors while receiving isoflurane and N2O anesthesia. The comparable incidence of intervention-related tight brain also supports the validity of the methodology employed in our study to identify patients with tight brain. We did not measure ICP or cerebrospinal fluid pressure during surgery. Turner et al.16 reported that there is a poor correlation between lumbar cerebrospinal fluid pressure and brain relaxation for pressure values within the normal range. We relied on clinical evaluation because we wanted to test how the two anesthetics influenced brain relaxation during surgical operation in the usual clinical scenario. Our study did not address the effects of desflurane or sevoflurane in patients with severe intracranial hypertension. Our patient population, in common with many neurosurgical practices, included a majority of patients who had well compensated ICP.
In conclusion, patients who received desflurane had a shorter extubation and early recovery time but similar intraoperative and postoperative incidence of complications compared with those who received sevoflurane.
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