Cortical resection for the management of refractory seizures or cerebral lesions located in close proximity to eloquent areas of the brain is often performed with the patient awake. Anesthesia is usually provided using a combination of local anesthesia (local infiltration and regional blockade) and intravenous (IV) medications to provide sedation, anxiolysis, and supplemental analgesia during these long procedures.
The need to minimize interference with intraoperative electrocorticography (ECoG), when this is used, limits the repertoire of drugs available for sedation. Traditionally, neurolept analgesia using a combination of opioid (often fentanyl) and droperidol has been a popular technique [1,2]. Recently, the use of propofol sedation during these procedures has been reported [3,4] and has become popular at our hospital.
Patient-controlled sedation (PCS) with propofol, using patient-controlled analgesia (PCA) technology, has been reported to be safe, to provide effective sedation, and to be associated with a high degree of patient satisfaction and acceptance [5-7]. Most of the available data involving PCS relate to surgical procedures of relatively short duration.
This prospective, randomized study was designed to evaluate the safety and efficacy of propofol PCS during awake craniotomy for seizure surgery. The impact of propofol sedation on intraoperative ECoG is addressed in an accompanying article.
After institutional ethics approval and acquisition of written, informed consent, adult patients (aged 18-65 yr) scheduled for cortical resection for refractory seizures were randomized to receive either propofol PCS or neurolept analgesia (fentanyl and droperidol).
Sedation for the PCS group consisted of patient-administered propofol using a bolus dose of 0.5 mg/kg, a lockout interval of 3 min, and a basal infusion of 0.5 mg [centered dot] kg-1 [centered dot] h-1 via a standard PCA device (Baxter, McGaw Park, ILPCAII). Patients were shown how to use the device preoperatively and were instructed to administer sedation if they wished to be more "sleepy" or if they experienced anxiety or discomfort. Patients were encouraged to use the PCS device early in the operative procedure (to ensure that they understood how to use it and what effect it would have on them) and were reminded that they could use the pump if they requested more sedation or became restless during the operation. They were also told that supplemental analgesia was available from their anesthesiologist if they were uncomfortable and that the anesthesiologist would take over administration of sedation if they were unable or unwilling to do so at any point in the operation. To avoid potential interference with ECoG recordings, propofol administration (both the PCS boluses and the basal infusion) was suspended 15 min prior to ECoG recording and functional cortical mapping.
For the neurolept group, sedation consisted of initial IV boluses of droperidol (0.04 mg/kg) and fentanyl (0.7 micro g/kg) followed by an anesthesiologistcontrolled continuous infusion of fentanyl at 0.7 micro g [centered dot] kg-1 [centered dot] h-1. Administration of supplemental droperidol was performed at the discretion of the attending anesthesiologist.
Both groups received supplemental anesthesiologistadministered fentanyl (25-micro g boluses) and dimenhydrinate (25-mg boluses) as needed for intraoperative pain and nausea or vomiting, respectively.
Regional blockade of the scalp was performed by the surgeon 1-2 h preoperatively using bupivacaine 0.5% with epinephrine. Supplemental local anesthetic solution (bupivacaine 0.33% with epinephrine) was used to infiltrate along the incision lines prior to surgery. During craniotomy, dura mater was anesthetized using a mixture of lidocaine 1% and 0.25% bupivacaine without epinephrine. Our block technique for craniotomy under local anesthesia has been previously described in detail .
All patients received supplemental oxygen via nasal prongs during surgery. Intraoperative monitoring included ECG, pulse oximetry, noninvasive automated blood pressure measurements, and capnography via the nasal prongs.
On the day before surgery, patients were visited to obtain demographic data and to perform baseline cognitive function and memory testing. Memory for objects was evaluated using recall and recognition tests preoperatively, intraoperatively (at 1 h after the commencement of sedation), postoperatively in the postanesthesia care unit (PACU), and on postoperative day (POD) 1. Memory was also evaluated on POD 1 and 2 by free recall of specific intraoperative events. Cognitive functioning was assessed preoperatively, intraoperatively at 1 h, in the PACU, and on POD 1 using examination questions listed in Appendix 1 Table 4.
Intraoperative sedation was assessed prior to sedation (baseline) and then hourly by the attending anesthesiologist based on a 5-point scale (Appendix 2 Table 5). The technical difficulty associated with each surgical procedure was evaluated by the attending surgeon based on a 5-point scale (technically easy = 1, technically difficult = 5).
Intraoperative and postoperative complications were noted. These included hemodynamic instability (systolic blood pressure <85 or >170 mm Hg, heart rate <45 or >110 bpm), decreased ventilatory frequency (<8 bpm), pulse oximetric desaturation (<90%), intraoperative vomiting, and inappropriate seizures (seizures not associated with ECoG recording or cortical mapping). The ability to perform appropriately during cortical mapping was also noted. Patient satisfaction was evaluated using a short questionnaire completed by each patient in the PACU and on PODs 1 and 5 (Appendix 3 Table 6).
Nonparametric data (e.g., the incidence of complications) were analyzed using Fisher's exact test or chi squared analysis. The unpaired Student's t-test was used to analyze parametric data (e.g., drug dose comparisons between groups). Satisfaction questionnaire and cognitive function test results were reported in parametric terms and analyzed using Students t-test. Identical results were obtained using nonparametric methods (Mann-Whitney U-test). Sedation scores were analyzed parametrically using analysis of variance for repeated measures and the Student-Newman-Keuls test. To confirm the acceptability of parametric analysis methods, the sedation scores were also subjected to nonparametric analysis, which yielded identical results. A level of P <or=to 0.05 was accepted as statistically significant.
Thirty-seven adult patients scheduled for cortical resection for refractory seizures were studied; 20 received propofol PCS, and 17 received neurolept analgesia. Three additional patients were excluded from the study because they required general anesthesia. One patient in the propofol group was converted to general anesthesia 1.5 h after the commencement of sedation due to incomplete regional blockade that could not be remedied during dural opening. Two patients in the neurolept group were converted to general anesthesia due to marked anxiety and agitation. For one patient, general anesthesia was induced prior to sedation; for the other patient, anesthesia was induced approximately 30 min after the commencement of sedation. In both cases, the patients were unwilling to continue the procedure awake and requested general anesthesia.
Demographic data for the two groups are shown in Table 1. The duration of anesthesia and surgery averaged 5-6 h. The majority of patients underwent temporal lobectomy.
Preoperative anticonvulsant medications were similar between groups. Thirty-five percent and 45% of the patients in the PCS and neurolept groups, respectively, received the usual dose of anticonvulsant medications on the morning of surgery. The remainder of the patients had anticonvulsant medications tapered, partially or completely, during preoperative evaluations and received a reduced dose or no dose of anticonvulsant medication on the day of surgery.
All patients received supplemental anesthesiologist-administered fentanyl for discomfort during the cortical resection. The supplemental dose was similar for the two groups (Table 2). The PCS patients received a mean propofol dose of 690 +/- 287 mg, of which 494 +/- 291 mg (72%) was patient-administered.
Adjustments to predetermined dose regimens (increases in the rate of the fentanyl infusion or increases in the bolus dose or basal infusion of propofol) were required for five patients in the neurolept group and four patients in the PCS group. Three of the patients in the PCS group had the propofol bolus dose increased to 0.75-1.0 micro g/kg. The fourth PCS patient was converted to a propofol infusion (2-3 mg [centered dot] kg-1 [centered dot] h-1) in response to a request to stop using the PCS device, which was prompted by discomfort and fatigue during the terminal stages of the cortical resection. In the neurolept group, the fentanyl infusion was increased to 0.9-1.8 micro g [centered dot] kg-1 [centered dot] h-1 for five patients. In addition to an increased fentanyl infusion, one of these patients also received incremental doses of propofol (10- to 20-mg boluses, total dose 240 mg over a 1.5-h interval) at the discretion of the attending anesthesiologist to manage agitation during the terminal aspects of the resection and closure. Three patients also received a single supplemental dose of droperidol ranging from 0.5 to 1.25 mg. Dose adjustments, if needed, typically reflected a response to restlessness or discomfort, often compounded by nausea, which may accompany resection of the mesial temporal lobe or basal frontal lobe. The predetermined sedation protocol, which included the suspension of propofol administration during testing, was not altered in either group during the preresection period (i.e., prior to or during ECoG recording).
Compared with baseline, sedation scores increased in a similar fashion in both groups except at the 2-h assessment, at which point sedation scores in the propofol group decreased significantly. This assessment coincided with the period during which propofol administration was suspended during intraoperative testing (Figure 1).
Memory and Cognitive Functioning
Based on recall and recognition tests, memory for objects was not different between the two groups (Figure 2). Memory encoding and retrieval were not affected substantially by either type of sedation. Cognitive function test results were similar between the two groups. Free recall of intraoperative events was not depressed in either group.
Patient satisfaction was similar between groups with respect to the general level of comfort and willingness to repeat the procedure using the same sedation technique (Table 3). Satisfaction with the option of self-administering sedation (assessed only in the PCS group) was high. Satisfaction with PCS was maintained through the fifth postoperative day.
Transient decreases in respiratory rate (<8 bpm) after supplemental doses of fentanyl were more common in the PCS group (P0.04, Fisher's exact test) (Table 2). These episodes were short in duration (<1 min) and did not require intervention. One patient in the neurolept group experienced a brief episode of pulse oximetric desaturation (SpO2 89%) associated with the administration of small doses of propofol during neurolept analgesia to manage agitation (as discussed previously).
Intraoperative inappropriate seizures were markedly more common in the neurolept group (P = 0.002, Fisher's exact test). Five patients experienced generalized convulsions, and two experienced focal motor seizures. Four of the patients who experienced generalized convulsions received IV thiopental (50- to 75-mg boluses) to terminate the seizures (mean dose 125 mg, range 50-200 mg). Each patient recovered satisfactorily to complete the procedure under neurolept analgesia. ECoG recordings were satisfactory in both groups, although a low frequency of ECoG spike activity noted in one of the patients in the neurolept group was attributed to the administration of thiopental to terminate a seizure that occurred during the period preceding ECoG recording. The frequency of ECoG spike activity did not correlate with the type of sedation administered, as discussed in detail in the accompanying article. All patients performed satisfactorily during functional cortical mapping.
Two patients in the PCS group and six patients in the neurolept group developed tachycardia in excess of 110 bpm in response to intraoperative discomfort (P = 0.07, Fisher's exact test) (Table 2). In all cases, this response was satisfactorily attenuated with supplemental fentanyl. The incidence of intraoperative vomiting and the administration of antiemetic medication were similar between the two groups.
Sedation during awake craniotomy has traditionally been provided using a combination of fentanyl and droperidol. Propofol offers several potential advantages over traditional techniques: its short duration of action facilitates titration of sedation, it has a wide spectrum of applications (including conversion to general anesthesia if clinical circumstances warrant), and it has been reported to have both antiemetic and amnestic properties at sedative doses [9-12].
Several studies [5,6,13,14] have endorsed the use of propofol for sedation during procedures of short duration, both by continuous infusion and via PCA delivery systems. Although the use of propofol sedation has been reported during epilepsy surgery [3,4], there is no information available regarding the safety or efficacy of patient-administered propofol sedation during these procedures. PCS offers the opportunity to combine bolus doses of sedative medication administered by the patient with a continuous basal infusion controlled by the anesthesiologist. This strategy offers the patient a sense of control and provides the capacity to administer sedation in response to the individual needs of the patient while enabling the anesthesiologist to determine the background level of sedation.
Our results demonstrate that patient-administered propofol is just as effective as anesthesiologist-administered neurolept analgesia during these procedures. Patients achieved similar levels of sedation and were similarly satisfied with both techniques. Patients using PCS were satisfied with the option of controlling the administration of sedation.
Based on our experience, the inclusion of a basal infusion is advantageous during propofol PCS for long procedures during which patients often become restless or fatigued as the procedure progresses . A basal infusion provides a baseline level of sedation that patients may augment using PCS demands in response to clinical circumstances. The PCS demand ratio in this study was 40%. This is consistent with the results of other investigators [7,16]. Although the technique is associated with a relatively high number of ineffective demands, patients achieved effective levels of sedation and expressed a high degree of satisfaction with PCS. These findings probably reflect a favorable response to the sense of control or participation provided by PCS.
Propofol may exert a positive or euphoric effect on mood [17-19], which has been postulated to contribute to the high levels of patient satisfaction reported with PCS, particularly when assessments are conducted intraoperatively or during the early postoperative period [6,14]. Our results suggest that patient satisfaction with propofol PCS is independent of these effects, if they exist, since satisfaction is maintained well into the postoperative period, up to POD 5.
Complications associated with the two sedation techniques were similar. A higher incidence of transient respiratory rate depression was found in the propofol group after doses of supplemental fentanyl. However, the fact that these events were not associated with pulse oximetric desaturation emphasizes the advantage associated with providing supplemental oxygen during these procedures. Patients receiving propofol sedation appear to be prone to respiratory depression associated with the administration of opioids. This observation has also been reported by others .
Patients receiving neurolept analgesia experienced a higher incidence of inappropriate intraoperative seizures compared with the patients who received propofol. Since the management of anticonvulsant medications in the preoperative period was similar between the two groups, these findings suggest that propofol may suppress seizure activity or that neurolept analgesia may either facilitate seizures or at least permit normal convulsions. Although its proconvulsant and anticonvulsant profile remains controversial, propofol has anticonvulsant activity at sedative doses . In contrast, many neuroleptic drugs, including butyrophenones such as droperidol, have been reported to lower the seizure threshold, and caution has been advised when administering these drugs to patients with untreated epilepsy [22,23]. The facilitation of seizure activity has not been reported in association with the administration of droperidol during anesthesia for intractable epilepsy . However, comparative studies involving the use of distinctly different sedation techniques during epilepsy surgery have not been reported previously. Further investigations are needed to define the basis for the observed difference in the incidence of seizures.
ECoG recordings were satisfactory to proceed with resection in all patients. A comparison of the ECoG effects of each of the sedation protocols is addressed in the accompanying article.
Propofol reportedly has significant antiemetic properties , but the incidence of intraoperative vomiting and the administration of dimenhydrinate were similar between our two groups. This may be because droperidol also possesses antiemetic properties, or because intraoperative vomiting was preempted by the administration of dimenhydrinate in response to complaints of nausea. An additional possibility may relate to the fact that many episodes of vomiting during these operations appear to result from discomfort associated with traction on blood vessels or dura at the base of the cortical resection. Although propofol and droperidol are effective antiemetics for drug-induced nausea and vomiting mediated by the area posterema, the mechanisms for intraoperative vomiting during these procedures may be less responsive to therapy.
Cognitive function was well preserved in both groups, as was memory. Patients in both groups performed well on formal memory testing involving object recall and recognition and demonstrated little amnesia for intraoperative events. Although propofol has been reported to possess amnestic properties at higher sedation doses, our findings, consistent with the results of other investigators, show that at lower doses, the amnestic effects of propofol are negligible [10,12,19].
The results of this study demonstrate that propofol PCS provides an effective alternative to neurolept analgesia during craniotomy performed under regional anesthesia. Our experience regarding the effect of propofol sedation on the quality of intraoperative ECoG recordings is described in the accompanying article.
The authors gratefully acknowledge the assistance of Ms. C. Hawke, Ms. L. Szabo (secretarial assistance), and Mr. P. Lok (data analysis) in the preparation of this manuscript.
1. Gignac E, Manninen PH, Gelb AW. Comparison of fentanyl, sufentanil and alfentanil during awake craniotomy for epilepsy. Can J Anaesth 1993;40:421-4.
2. Archer DP, McKenna JMA, Morin L, Ravussin P. Conscioussedation analgesia during craniotomy for intractable epilepsy: a review of 354 consecutive cases. Can J Anaesth 1988;35:338-44.
3. Silbergeld DL, Mueller WM, Colley PS, et al. Use of propofol (Diprivan) for awake craniotomies: technical note. Surg Neurol 1992;38:271-2.
4. Drummond JC, Iragui-Madoz VJ, Alksne JF, Kalkman CJ. Masking of epileptiform activity by propofol during seizure surgery. Anesthesiology 1992;76:652-4.
5. Rudkin GE, Osborne GA, Curtis NJ. Intra-operative patient-controlled sedation. Anaesthesia 1991;46:90-2.
6. Grattidge P. Patient-controlled sedation using propofol in day surgery. Anaesthesia 1992;47:683-5.
7. Ghouri AF, Taylor E, White PF. Patient-controlled drug administration during local anesthesia: a comparison of midazolam, propofol and alfentanil. J Clin Anesth 1992;4:476-9.
8. Girvin JP. Neurosurgical considerations and general methods for craniotomy under local anesthesia. Int Anesthesiol Clin 1986;24:89-113.
9. Borgeat A, Wilder-Smith OHG, Saiah M, Rifat K. Subhypnotic doses of propofol possess direct antiemetic properties. Anesth Analg 1992;74:539-41.
10. Smith I, Monk TG, White PF, Ding Y. Propofol infusion during regional anesthesia: sedative, amnestic, and anxiolytic properties. Anesth Analg 1994;79:313-9.
11. Veselis RA, Reinsel RA, Wronski M, et al. EEG and memory effects of low-dose infusions of propofol. Br J Anaesth 1992;69:246-54.
12. Zacny JP, Lichtor JL, Coalson DW, et al. Subjective and psychomotor effects of subanesthetic doses of propofol in healthy volunteers. Anesthesiology 1992;76:696-702.
13. Mackenzie N, Grant IS. Propofol for intravenous sedation. Anaesthesia 1987;42:3-6.
14. Osborne GA, Rudkin GE, Jarvis DA, et al. Intra-operative patient-controlled sedation and patient attitude to control. Anaesthesia 1994;49:287-92.
15. Park WY, Watkins PA. Patient-controlled sedation during epidural anesthesia. Anesth Analg 1991;72:304-7.
16. Osborne GA, Rudkin GE, Curtis NJ, et al. Intra-operative patient-controlled sedation: comparison of patient-controlled propofol with anaesthetist-administered midazolam and fentanyl. Anaesthesia 1991;46:553-6.
17. Whitehead C, Sanders LD, Oldroyd G, et al. The subjective effects of low-dose propofol. Anaesthesia 1994;49:490-6.
18. Oxorn D, Orser B, Ferris LE, Harrington E. Propofol and thiopental anesthesia: a comparison of the incidence of dreams and perioperative mood alterations. Anesth Analg 1994;79:553-7.
19. Pratila MG, Fischer ME, Alagesan R, et al. Propofol versus midazolam for monitored sedation: a comparison of intraoperative and recovery parameters. J Clin Anesth 1993;5:268-74.
20. Allan MWB, Laurence AS, Gunawardena WJ. A comparison of two sedation techniques for neuroradiology. Eur J Anaesthesiol 1989;6:379-84.
21. Herrick IA. Seizure activity and anesthetic agents and adjuvants. In: Albin MS, ed. Textbook of neuroanesthesia with neurosurgical and neuroscience perspectives. New York: McGraw Hill, 1997:615-42.
22. Baldessarini RJ. Drugs and the treatment of psychiatric disorders. In: Gilman AG, Goodman LS, Rall TW, Murad F, eds. The pharmacological basis of therapeutics. 7th ed. New York: Mac-Millan, 1985:396.
23. Canadian Pharmaceutical Association. Inapsine (droperidol) [monograph]. In: Compendium of pharmaceuticals and specialties. 31st ed. Ottawa: Canadian Pharmaceutical Association, 1996:666.