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Patient Satisfaction with Awake Craniotomy for Tumor Surgery: A Comparison of Remifentanil and Fentanyl in Conjunction with Propofol

Section Editor(s): Warner, David S.Manninen, Pirjo H. MD*; Balki, Mrinalini MD*; Lukitto, Karolinah MD*; Bernstein, Mark MD

doi: 10.1213/01.ANE.0000181287.86811.5C
Neurosurgical Anesthesia: Research Report
Chinese Language Editions

In this study we compared the effectiveness of the use of remifentanil to fentanyl in conjunction with propofol in providing conscious sedation for awake craniotomy for tumor surgery and to assess patient satisfaction with both techniques. The ability to maintain appropriate levels of sedation, adequate analgesia, and hemodynamic stability was assessed in 50 patients randomized to receive either fentanyl or remifentanil. All complications were documented. Patients were interviewed at 1 h, 4 h, and 24 h after surgery to note their recall of procedure and pain and their overall satisfaction. There were no differences in sedation and pain scores or in hemodynamic and respiratory variables between the two groups. The incidence of intraoperative complications was not different (fentanyl, 14; remifentanil, 16). Respiratory complications occurred in 9 (18%) patients (fentanyl 6, remifentanil 3). The recall and satisfaction scores were not different; 93% of all patients were completely satisfied at all interview times. The use of remifentanil infusion in conjunction with propofol is a good alternative to fentanyl and propofol for conscious sedation for the awake craniotomy and these techniques are both well accepted by the patient.

IMPLICATIONS: The use of remifentanil and propofol when compared with fentanyl and propofol was not different in the ability to maintain adequate sedation, analgesia, and hemodynamic stability or in the incidence of complications during awake craniotomy for tumor surgery. Patient satisfaction was high for both techniques.

Departments of *Anesthesia and †Neurosurgery, Toronto Western Hospital, University Health Network, University of Toronto, Toronto, Ontario

Accepted for publication July 20, 2005.

Address correspondence to Pirjo Manninen, MD, Department of Anesthesia, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario Canada MST 258. Address e-mail to

Awake craniotomy for tumor surgery is an accepted procedure that provides an opportunity for mapping of eloquent brain function, such as speech, motor, and sensory, to minimize neurological injury during tumor resection (1–3). The level of sedation and analgesia required during the different stages of surgery varies greatly; most importantly the patient needs to be awake and alert during mapping of the brain. Numerous combinations of sedation, analgesia, and anesthetic techniques have been described ranging from general anesthesia, with the insertion of an airway device, to monitored anesthesia care (4–13). The most common anesthetic used is propofol with or without opioids (14). More recently remifentanil has been introduced as an alternative to fentanyl (4,6,8). In our institution we routinely use conscious sedation with no manipulation of the patient's airway. Patient tolerance and acceptance of the awake craniotomy has been questioned (1). It is uncertain whether the selection of anesthetics plays a role in the ability of patients to tolerate an awake craniotomy and to recall intraoperative events. The purpose of this study was to compare the effectiveness of the administration of remifentanil plus propofol infusions to intermittent fentanyl and propofol infusion in providing conscious sedation for tumor surgery. The primary end-points were to assess the ability to maintain appropriate levels of sedation and analgesia and hemodynamic stability intraoperatively and to assess patient satisfaction with both anesthetic management protocols.

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After institutional ethics board approval and written patient consent, 50 patients were randomized to receive either fentanyl or remifentanil in addition to propofol infusion for conscious sedation during awake craniotomy. Patients were assessed in the preoperative consultation clinic and informed of our anesthetic management. No preoperative sedation was administered. On arrival in the operating room routine monitoring included an electrocardiogram, noninvasive arterial blood pressure, pulse oximetry, and end-tidal carbon dioxide and respiratory rate measured via an oxygen delivery nasal prongs port. Supplemental oxygen was delivered at 4 L/min. According to our routine practice invasive monitoring, including urinary catheter, was not used. All patients received IV midazolam 15 μg/kg after they were placed on the operating table in the correct position for surgery (lateral or supine) using extra cushions and padding to ensure maximum patient comfort. Both groups were started on an infusion of propofol (75–100 μg · kg−1 · min−1) and administered fentanyl (0.5–1 μg/kg) bolus or remifentanil infusion (0.03–0.05 μg · kg−1 · min−1), depending on randomization. The sites of pin insertion for rigid head fixation were infiltrated with local anesthesia (lidocaine 2% with 1:200,000 epinephrine) by the surgeon. After fixation the propofol infusion was briefly stopped to ensure patient comfort with head positioning and then restarted. The aim of the conscious sedation during most of the procedure was to maintain the level of sedation at a sedation score of three of the Modified Observer's Assessment of Alertness/Sedation scale (15). At this level the patients will respond after their name is called loudly or repeatedly. At any time during the procedure when excessive pain was expected, such as the infiltration of the local anesthetic into the pin sites and scalp, additional anesthesia was given by increasing the propofol infusion and/or increasing the remifentanil infusion or fentanyl bolus (25–50μg) depending on randomization. Scalp infiltration was with 0.25% bupivacaine with 1:200,000 epinephrine. Maintenance IV fluids consisted of normal saline at the rate of 50 to 100 mL/h. Approximately 5 min before brain mapping both propofol and opioids were discontinued. After completion of the mapping, the predetermined conscious sedation technique was resumed for tumor resection and closure. All patients received fentanyl 1–2 μg/kg for postoperative analgesia at the time of skin closure. Patients were transferred to the postanesthetic care unit (PACU) for a 4-h stay before discharge to the ward or day surgery unit. Postoperative pain was treated with codeine IM, IV morphine, or fentanyl. IV granisetron or dimenhydrinate was given for nausea and vomiting if needed.

All intraoperative events, complaints, and complications were documented. During the procedure the following measurements were taken: sedation score (Modified Observer's Assessment of Alertness/Sedation scale, 0 to 5), pain score (0 no pain, 10 worst imaginable pain), arterial blood pressure, heart rate, oxygen saturation, and respiratory rate. These were documented at arrival in the operating room, during application of headpins, 5 min after headpin application, at skin incision, before brain mapping, during brain mapping, every 30 min during tumor resection, at closure during head dressing, and in PACU at 0, 15, and 30 min after arrival. Patient neurological status, all postoperative complications, duration of hospital stay, and outcome were documented

Postoperatively patients were interviewed by a blinded investigator (KL) at 1 h, 4 h, and 24 h after surgery regarding their experience. The patients were asked if and what they remembered about their intraoperative experience. If they had no recall, specific questions were asked such as “do you remember hearing drilling noises or did you have pain when the pins were inserted?” Each response was graded as no recall, partial (at least 2 events), or complete (more than 4 events). Patients were also assessed for their recall of intraoperative pain, discomfort, or anxiety. This was graded as none, mild (partial), or moderate and severe (complete). Patients were then asked about their overall satisfaction with the anesthetic management, and this was graded as complete satisfaction, partial, or not satisfied at all. If the patient had been discharged home the day of surgery, a telephone interview was conducted. Statistical analysis of the data was with Student's t-test for paired results and χ2. A P value of <0.05 was considered significant.

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All 50 patients completed the study. There were no differences in the demographics or in the overall anesthetic management between the two groups, as shown in Table 1, except for the doses of propofol and fentanyl. As expected from the protocol, the fentanyl group received a larger dose of fentanyl, but they also received a larger dose of propofol. One patient in the fentanyl group required an unusually large dose of propofol (3900 mg) for restlessness. There was no difference in the ability to maintain the appropriate level of sedation as follows: at 3 of the Modified Observer's Assessment of Alertness/Sedation scale during most of the procedure and close to 5 (fully awake and alert) during mapping (Table 2). The scores for pain and the hemodynamic and respiratory values did not differ between the two groups throughout the intraoperative or postoperative periods (Table 2). Cortical mapping for speech, motor, and/or sensory function was performed in 21 patients in the fentanyl and 23 in the remifentanil group with no difficulty. In six patients the surgeon deemed it not necessary after exposure of the brain and tumor site. In four patients mannitol was given electively by request from the surgeon and for one patient (remifentanil group) it was given for treatment of a tight brain.

Table 1

Table 1

Table 2

Table 2

During the awake craniotomy, 60% of the patients experienced no complications, and they did not voice any complaints (fentanyl, 15; remifentanil, 15). The total incidence of intraoperative complications/complaints was not different between groups, 14 in the fentanyl and 16 in the remifentanil group (Table 3). More than one complication occurred in three patients in the fentanyl and five patients in the remifentanil group. Respiratory complications occurred in total of 9 (18%) patients. In the fentanyl group, five patients developed decreased respiratory rate and mild airway obstruction during or just after the insertion of headpins. One patient also had a short period of oxygen desaturation (<90%). The propofol infusion was decreased in all patients and three needed a short period of manual jaw thrust. One patient (fentanyl group) during a long tumor resection was restless and with deepening of sedation developed recurrent airway obstruction (snoring) and required the insertion of a nasal airway. In the remifentanil group, three patients developed decreases in respiratory rate, decrease in oxygen saturation (<90%), and short periods of airway obstruction during adjustments in the infusion rate for remifentanil. Remifentanil infusion rates were decreased, but two patients needed a brief period of jaw thrust and the third also needed a short application of oxygen and ventilation by mask.

Table 3

Table 3

Nonrespiratory complications/complaints occurred in 4 patients (16%) in the fentanyl group and 7 (28%) in the remifentanil group (Table 3). Changes in cardiovascular variables that required treatment occurred in three patients. One patient in the fentanyl group who had a long procedure and was very restless also had increases in arterial blood pressure requiring the administration of labetalol and metoprolol. In the remifentanil group, one patient became hypotensive with the sudden loss of 400 mL of blood. This was treated with administration of IV fluids. The other patient in the remifentanil group developed a sudden onset of hypotension, which was immediately followed by a seizure. Treatment of the seizure with propofol corrected the hypotension. Preoperative seizures had occurred in 9 (36%) patients in the fentanyl group and in 10 (40%) in the remifentanil group. Intraoperative seizures occurred during mapping and tumor resection in four patients, all in the remifentanil group. Three of these patients had a history of preoperative seizures

On arrival in the PACU the patients' median Glasgow Coma Score for the fentanyl group was 15 (range, 14–15) and for remifentanil 15 (range, 14–15). There were no differences in sedation and pain scores or in the hemodynamic or respiratory variables in the PACU (Table 2). During the first postoperative hour pain in the fentanyl group was treated with codeine (mean ± sd) 62 ± 7 mg (n = 18 patients), fentanyl 52 ± 18 μg (n = 11), and morphine 6 mg (n = 1). In the remifentanil Group 16 patients received codeine 60 ± 0 mg and 9 patients received fentanyl 52 ± 43 μg.

Postoperative complications did not differ between the two groups (Table 3). New neurological deficits were present in five patients; in the fentanyl group two patients developed a visual field defect, one patient had transient aphasia, and in the remifentanil group one patient developed a persistent mild hemiplegia that started in the operating room and another patient had transient episodes of arm weakness that were related to seizure activity.

Patient recall of the procedure and of intraoperative pain and anxiety and satisfaction results are shown in Figure 1. There were no differences between the two groups. Most patients gave the same responses to the questions at the three different interview times. Only 1 patient changed his satisfaction score from an initial 1-h score of complete satisfaction to partial at 4 h and 24 h. Two patients recalled having severe intraoperative pain, but their highest intraoperative pain scores were 2 and 4 and neither had voiced any complaints of pain. The duration of stay in hospital did not influence the satisfaction scores. Eleven (22%) patients (fentanyl, n = 6; remifentanil, n = 5) were discharged home on the day of surgery. The mean (± sd) cost of the total amount of propofol, fentanyl, and remifentanil administered to the patients in each groups was not different (fentanyl group $11.29 ± $12.92 [US] and remifentanil $9.25 ± $4.28 [US]).

Figure 1

Figure 1

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In our study, we found that the use of both conscious sedation techniques, remifentanil plus propofol infusions and intermittent fentanyl with propofol infusion, were similar with respect to intraoperative management and in the incidence of intraoperative and postoperative complications. Overall, 93% of the patients were completely satisfied with their anesthetic management.

There is considerable variation in the anesthetic techniques of the “awake craniotomy” (4–13). They range from the “asleep-awake-asleep” techniques, with or without the use of an airway, to those of monitored anesthesia care or conscious sedation. Most institutions have developed their own methods for providing anesthesia for these procedures depending on the needs of their surgeons and their patient population. During the procedure frequent changes in the depth of sedation/anesthesia are needed to prevent complications such as excessive pain or respiratory depression. An alert and cooperative patient is essential for adequate functional testing. Propofol has been frequently used and more recently remifentanil has also been used (4,6,8,14). Johnson and Egan (4) published a case report of propofol and remifentanil infusion using computer simulation. The advantage of remifentanil was a rapid reversal of narcosis when intraoperative consciousness was required. Another case report by Hans et al. (6) described the use of a target-controlled administration of propofol and remifentanil, which allowed them to adjust drug administration according to painful stimulation and functional testing. Berkenstadt et al. (8) reported on the use of remifentanil with propofol in 25 patients. Although their patients had stable hemodynamic profiles, there was a more frequent incidence of respiratory depression in the first 10 patients. The incidence of respiratory complications improved over the course of the study probably the result of more careful adjustment of the drugs.

In our study we also found that the combination of remifentanil and propofol was effective in maintaining the appropriate level of sedation and control of pain as well as hemodynamic stability. The results for remifentanil did not differ from the use of fentanyl and propofol. The failure to find a difference between the two groups in our study may have been attributable to the small sample size studied. Our sample size was calculated on the basis of our hypothesis of a 10% reduction for intraoperative pain with remifentanil using α of 0.05 and power of 0.8. To show no difference that is significant with adequate power, 600 patients would be required for each group. In our study we also did not vigorously regulate the doses of the anesthetics given to each patient. It was left up to the anesthesiologist as to which drug was administered for pain and anxiety. The mean dose of propofol used in the fentanyl group was larger than that used in the remifentanil group in our study, but this result was skewed by one patient who required an excessively large dose for restlessness. The overall cost of anesthetics used in each group was not different; however, we did not calculate the cost of the portion of drug from each vial that was wasted.

There is reluctance to perform awake craniotomy procedures for fear of complications. There is limited information in the literature with respect to the incidence of complications during an awake craniotomy for tumor surgery. Respiratory complications are feared the most, especially when there is an unprotected airway. Sarang and Dinsmore (11) reported an incidence of 7% airway obstruction in a group of 46 patients with sedation and a nasopharyngeal airway. The airway obstruction was treated with jaw thrust or manual support. In our study, airway complications occurred in 18% (9 patients). All these events were easily treated and there was no difference between the two groups. Respiratory complications can be anticipated during an awake craniotomy when the airway is not secured. It is difficult to always predict the correct dose of a drug in an awake and anxious patient. These periods of respiratory depression are usually very brief, because of the short-acting drugs used, and are easily treatable by decreasing the drug administration and/or by a short chin lift or jaw thrust. However, whatever technique of awake craniotomy is used, it is essential for the anesthesiologist to have a plan of action and the necessary equipment to deal with all airway complications.

The incidence of nonrespiratory complications/complaints was frequent (22%), but we were looking for all complications including voiced complaints, as we were also interested in the satisfaction experience of our patients. Most of these complications were short in duration and easily treated, such as two patients who complained of being cold and were given warming blankets. New onset of seizures is a common presentation for a patient with a brain tumor and thus seizures may occur at any time. Seizures that occur while rigid head fixation is used can be frightening. Most intraoperative seizures occur during mapping or tumor resection and are of short duration. They can be quickly treated with small doses of propofol. In our study, all the patients with intraoperative seizures were in the remifentanil group; however, because the numbers are small it is not possible to determine whether the presence of remifentanil played a role. There were no incidences of intraoperative nausea or vomiting. The restless or disinhibited patient is of great concern and treatment may lead to further complications, such as airway obstruction with increased sedation. In our study one patient required insertion of a nasal airway, but the induction of general anesthesia was not required in any patient. In a previous report from our institution in 241 patients there was only one conversion to general anesthesia after a generalized seizure (16). In a series of 150 patients, Nikas et al. (3) reported that the majority of patients did not have any anesthetic complications, and those that did experience complications were easily treatable. Only one patient required conversion to general anesthesia. The incidence of neurological deficits in our study was 10%, but it was not our intent to evaluate the role of the awake craniotomy in preventing neurological injury.

We also assessed the overall satisfaction of the patients' experience and their recall during both of these anesthetic techniques. We found that most patients were completely satisfied with their experience at all times of questioning. There was no difference between the two groups. Patients who stated that they had complete recall for intraoperative events were completely satisfied with their experience. The incidence of severe pain during the procedure and the recall of pain postoperatively were infrequent; 56% of the patients recalled mild pain and 22% recalled no pain at all times of interviewing. A reason for the high satisfaction rate may be that our patients were preselected by their surgeons for this procedure and were also well prepared for it by the surgeon and anesthesiologist. Our findings on the subjective experience of patients were similar to those of Danks et al. (1). They interviewed their patients 2 or 3 days postoperatively and included a psychiatric assessment at 1 month. Initially, about one half of their patients did not recall intraoperative pain and were satisfied with their experience. At 1 month all patients were comfortable with the experience.

The awake craniotomy for tumor surgery has become well established, although the anesthetic management will continue to differ at each institution. Complications, especially respiratory, will occur in some patients, but treatment can be readily accomplished. Continuous vigilance is absolutely necessary. The use of remifentanil infusion in conjunction with propofol is a good alternative to fentanyl and propofol for conscious sedation for the awake craniotomy, and these techniques are both well accepted by patients.

The authors wish to thank the Toronto Western Hospital neurosurgeons for their cooperation with this study and Dr. Hossam El-Beheiry for his assistance in statistical analysis.

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