A Comparison Between Scalp Nerve Block and Morphine for Transitional Analgesia After Remifentanil-Based Anesthesia in Neurosurgery

Christian Ayoub, MD, B. Pharm* Francois Girard, MD, FRCPC* Daniel Boudreault, MD, FRCPC* Philippe Chouinard, MD, FRCPC* Monique Ruel, RN* Robert Moumdjian, MD, FRCS(C)
We compared transitional analgesia provided by scalp nerve block (SNB) or morphine after remifentanil-based anesthesia in neurosurgery. Fifty craniotomy patients were randomly divided into two groups: morphine (morphine 0.1 mg kg 1 IV after dural closure and an SNB performed with 20 mL of 0.9% saline at the end of surgery) and block (10 mL of 0.9% saline instead of morphine after dural closure and an SNB performed with a 1:1 mixture of bupivacaine 0.5% and lidocaine 2% at the end of surgery). Postoperative pain was assessed at 1, 2, 4, 8, 12, 16, and 24 h using a 10-point numerical rating scale. Analgesia consisted of subcutaneous codeine. Average numerical rating scale scores were similar between the two groups at each time interval. Total codeine dosage was also similar, except at 4 h postoperatively when it was higher in the block group. The delay before administration of the first dose of codeine was not statistically different between groups: 45 min (20 2880) vs 30 min (10 2880), median and range for the block and morphine group, respectively. Postoperative hemodynamics were similar for both groups. The incidence of nausea and vomiting was slightly more frequent in the morphine group, but the occurrence of confusion did not differ between groups. In conclusion, SNB provides a quality of transitional analgesia that is similar to that of morphine with the same postoperative hemodynamic profile.
(Anesth Analg 2006;103:123740)

emifentanil is a suitable alternative to fentanyl or sufentanil for intracranial surgery and it allows quick neurological recovery (1 4). However, the very short duration of action of remifentanil requires a transition method for analgesia to ensure a smooth and pain-free emergence from general anesthesia. When transitional analgesia is not used, patients anesthetized with remifentanil require pain medication much earlier and tend to have more frequent early postoperative hypertension (3,4). Our group (5) has demonstrated that postoperative scalp nerve block (SNB) decreases the severity of pain after craniotomy. To our knowledge, no study has assessed the use of this technique as a means of transitional analgesia after remifentanil-based anesthesia in intracranial surgery. We, therefore, designed this prospective, randomized, controlled, and double-blinded study to assess the quality of transitional analgesia provided by SNB

as compared with IV morphine, after general anesthesia consisting of remifentanil and sevoflurane for supratentorial craniotomy. We hypothesized that the use of SNB would result in lower pain scores, fewer opioid-associated side effects (confusion, nausea and vomiting), as well as a reduction in total opioid requirements in the first 24 h after surgery.

METHODS
After IRB approval and written informed consent, 50 patients, ASA IIII, 18 70 yr, and scheduled for an elective supratentorial craniotomy, were enrolled in this study. Exclusion criteria were inability to understand a numerical rating scale (NRS), proven or suspected allergy to local anesthetics or morphine, and a craniotomy incision extending beyond the field covered by the SNB. Patients chronically treated with opioid medications ( 2 wk), presenting with a history of alcohol abuse and with active psychiatric disorders were also excluded. Anesthesia was standardized for all patients. Patients were premedicated with midazolam 2 mg IV in the operating room. Anesthesia induction consisted of propofol (1.03.0 mg kg 1) and remifentanil (1.0 g kg 1). Tracheal intubation was facilitated with rocuronium (0.91.2 mg kg 1) or cisatracurium (0.150.20 mg kg 1). An infusion of remifentanil was started immediately after induction at a rate of 0.1 g kg 1 min 1. The remifentanil infusion rate was adjusted between 0.1 and
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From the *Department of Anesthesiology, and Neurosurgery division, CHUM, Hopital Notre-Dame, Montreal, Canada. Accepted for publication July 17, 2006. Supported in part by a Grant from the Canadian Anesthesiologist Society. Address correspondence and reprint requests to Francois Girard MD, FRCPC, Department of Anesthesiology, CHUM, Hopital Notre-Dame, 1560 Sherbrooke East, Montreal, Canada, H2L 4M1. Address e-mail to francois.girard.chum@ssss.gouv.qc.ca. Copyright 2006 International Anesthesia Research Society
DOI: 10.1213/01.ane.0000244319.51957.9f

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0.5 g kg 1 min 1, by increments or decrements of 0.1 g kg 1 min 1, to maintain the mean arterial blood pressure between 60 and 80 mm Hg and the heart rate within 20% of the baseline value. Anesthesia was maintained with sevoflurane (0.51.0 MAC) in oxygen and air (Fio2 0.40) along with the remifentanil infusion. The attending anesthesiologist was asked to keep the sevoflurane-inspired concentration close to 0.5 MAC and make adjustments with the remifentanil infusion first and then increase the sevoflurane concentration as necessary. Remifentanil 1.0 1.5 g kg 1 was given 1 min before the application of the Mayfields head holder to prevent a hemodynamic reaction. There was no infiltration of the scalp by the surgeon. Muscle relaxants were used as needed to maintain a single twitch on train-offour stimulation. Patients were randomly divided into two groups using sealed envelopes. Patients in the morphine group received morphine 0.1 mg kg 1 IV, diluted in 10 mL of normal saline after dural closure and a SNB was performed with 0.9% normal saline (placebo) instead of the local anesthetic mixture (compare Scalp Nerve Block section) at the end of surgery. For patients in the block group, 10 mL of 0.9% normal saline (placebo) was given IV after dural closure instead of morphine, and a SNB was performed using the same technique with bupivacaine and lidocaine at the end of the procedure. The syringes were prepared by an anesthesiologist not involved in the study or care of study patients.

Table 1. Demographic and Preoperative Data Group block (n 25)

Male:female Age Weight Corticosteroids (cerebral edema prophylaxis) Acetaminophen (for postoperative fever) Preoperative diagnosis Tumor Neurovascular Epilepsy Meningioma 14:11 51 14 69.1 15.6 18 6 15 2 3 5

Group morphine (n 25)

15:10 47 12 77.8 14.0 19 4 14 1 2 8

Table 2. Intraoperative Data Group block (n 25)

Body temperature Baseline MAP (mm Hg) Sevoflurane (MAC-h) Remifentanil (total, mg) Duration of surgery (h) Types of craniotomy Frontal Fronto-temporal Temporal Parietal
MAP tion *P mean arterial blood pressure; MAC-h duration of exposure). 0.01.

Group morphine (n 25)

36.0 72.2 4.4 7.6 7.3 9 6 7 3 0.6 3.6 2.6* 5.3 3.9

35.9 68.9 3.3 5.4 6.1 9 6 5 5

0.6 4.0 1.6 3.3 2.3

Scalp Nerve Block

The SNB was done bilaterally at the end of surgery while the patient still under general anesthesia and before removal of the head holder. The block was performed by a blinded investigator according to a technique previously described by Pinosky et al. (6) and used later by our group (5). The anesthetic solution consisted of a mixture of 10 mL of lidocaine 2% and 10 mL of bupivacaine 0.5% (group block) or 20 mL of 0.9% saline (group morphine). The supraorbital and supratrochlear nerves were blocked with 2 mL of solution as they emerged from the orbit with a 25-gauge needle introduced above the eyebrow perpendicular to the skin. The auriculotemporal nerves were blocked with 3 mL of solution, 1.5 cm anterior to the ear at the level of the tragus. With the needle perpendicular to the skin, infiltration of 1.5 mL was made deep into the fascia and another 1.5 mL superficially as the needle was withdrawn. The postauricular branches of the greater auricular nerves were blocked with 2 mL of solution between skin and bone, 1.5 cm posterior to the ear at the level of the tragus. The greater, lesser, and third occipital nerves were blocked with 3 mL of solution by infiltrating along the superior nuchal line, approximately halfway between the occipital protuberance and the mastoid process. Patients were awakened and the trachea was extubated after completion of the block as they met standard extubation criteria.
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MAC-hour (minimum alveolar concentra-

Table 3. Median Pain Scores Group block

1h 2h 4h 8h 12 h 16 h 24 h 6 (010) 5 (09) 4 (09) 2 (08) 2 (010) 2 (08) 2 (09)

Group morphine
5 (010) 4 (09) 4 (08) 2 (07) 3 (07) 3 (07) 3 (08)

Median numerical rating scale with range in parenthesis (0 was dened as no pain and 10 the worst possible pain).

Postoperative Pain
Patients were asked to rate their pain using a 10points NRS (0 was defined as no pain and 10 the worst possible pain) at 1, 2, 4, 8, 12, 16, and 24 h postoperatively by a nurse trained with the technique. Cumulative doses of codeine, the incidence of nausea, and vomiting as well as periods of confusion were noted. Only NRS data obtained from patients who were fully oriented and with a Glasgow coma score of at least 14 were considered for statistical analysis. Codeine phosphate (30 60 mg) was given subcutaneously to treat pain as needed every 4 h. Acetaminophen was given only in case of fever. Nonsteroidal antiinflammatory drugs were not allowed during
ANESTHESIA & ANALGESIA

Table 4. Postoperative Data Group block

Delay before administration of codeine in minutes (median and range) Cumulative dosage of codeine (mg) 4h 12 h 24 h 48 h Percentage of patients with nausea and/or vomiting [cumulative n (%)] 4h 12 h 24 h Postoperative hemodynamics PACU arrival SBP HR 1 h postoperative SBP HR 2 h postoperative SBP HR
PACU postanesthesia care unit; SBP * P 0.05. systolic blood pressure; HR heart rate.

Group morphine
30 (102880) 53.4 113.6 212.4 338.8 38.7* 74.8 147.3 225.1

45 (202880) 78.6 144.8 217.8 325.0 44.1 71.7 153.2 257.0

12 (48) 12 (48) 13 (52) 142 81 142 76 134 79 19 9 17 11 16 10

13 (52) 17 (68) (P 18 (72) (P 148 90 139 79 137 83 19 (P 17 (P

0.15) 0.15) 0.32) 0.08)

18 (ns) 13 (ns) 15 (ns) 13 (ns)

the study period. We noted the delay before the first analgesic request in the postoperative period. Patients who did not request analgesic for the entire study period (48 h) were arbitrarily attributed a value of 2880 min.

Statistical Analysis
On the basis of our previous study, considering an value of 0.05 and a value of 0.2, we estimated that 23 patients in each group would be necessary to demonstrate a difference of 50% on the NRS, assuming that the average NRS for the first 24 h after surgery would be 3.9 3.0 for the morphine group and 1.95 2.2 for block group (5). Data were collected in an excel database. Results are expressed as the mean sd, except when stated otherwise. Differences in demographic and intraoperative data between the two groups were evaluated using the 2 test and unpaired Students t-test for nonparametric and parametric variables respectively. Differences in NRS scoring between groups and over time were evaluated using a repeated measure analysis of variance and t-tests. The interval of time between the end of surgery and the first administration of codeine was analyzed using unpaired Students t-test. A P value 0.05 was considered significant throughout.

RESULTS
Fifty-five patients were recruited for the study. Five patients were excluded before completion of the protocol because of intraoperative complications precluding immediate postoperative tracheal extubation. Fifty patients remained for analysis, 25 in each group. There was no difference in demographic and preoperative data between groups (Table 1). Intraoperative data were also comparable, with the exception of
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the total MAC-h of sevoflurane, which was longer in the morphine group (Table 2). This difference reached statistical significance because of a longer duration of surgery in the morphine group. The average sevoflurane concentrations were 0.54 and 0.6 respectively for the block and morphine groups. Three-hundred-forty-two NRS scores were available for analysis. Eight scores were excluded because of a Glasgow Coma Score 14; five in the block group and three in the morphine group. Median NRS values with a range for each time interval are provided in Table 3. There was no difference in the NRS score between groups over the 24-h period. Table 4 lists the cumulative doses of codeine as well as delay before the administration of the first dose of codeine. The difference in codeine dosage reached statistical significance only at 4 h postoperatively, with a lower dose in the morphine group. There was no difference between groups in postoperative hemodynamics at postanesthesia care unit arrival and at 1 and 2 h postoperatively (Table 4). Five patients in the block group and three patients in the morphine group received antihypertensive medication in the postanesthesia care unit. Patients in the morphine group appeared to have more nausea and vomiting at 12 and 24 h postoperatively, but this was not statistically significant. Intraoperative administration of dolasetron 12.5 mg IV for nausea and vomiting prophylaxis was used for one patient in each study group (protocol violation, the patients were not excluded).

DISCUSSION
In this study, we show that SNB provides transitional analgesia equivalent to that conferred by morphine 0.1 mg kg 1 IV given after dural closure. The
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occurrence of side effects usually associated with opioid administration was similar in both groups. On average, pain intensity was moderate in the first 4 postoperative hours and mild for the remaining 16 h. Some, but not all, studies using remifentanil as the baseline opioid for intracranial surgery used some form of transitional analgesia. Guy et al. (3) were the first to publish a study comparing remifentanil and fentanyl for intracranial surgery. They did not use transitional analgesia and found that patients in the remifentanil group required analgesia earlier than those in the fentanyl group, with no difference in the incidence of nausea and vomiting. Emergence hypertension was also more common in the remifentanil group. These pitfalls led the authors to believe that devising techniques to improve emergence and recovery analgesia was warranted. In a study with a similar design, Gelb et al. (2) showed that giving morphine 0.08 mg kg 1 IV at bone flap replacement did not affect the recovery profile in patients receiving a remifentanil infusion compared with those who received fentanyl. Remifentanil was superior in time to achieve preoperative neurological examination and quality of emergence. Remifentanil patients required analgesia earlier than fentanyl patients, but the analgesia provided by morphine was deemed adequate. There was no difference between the two groups in postoperative hemodynamics, nausea, and vomiting. The present study is, therefore, in agreement with the literature in that some form of transitional analgesia improves pain control as well as hemodynamics early in the recovery process of neurosurgical patients, and that SNB is equivalent to morphine in doing so (2,7,8).

In our study, the population of patients was limited to supratentorial craniotomies, since the field of the SNB does not cover the posterior fossa. This makes comparisons with other studies that include a broader group of patients more difficult. In conclusion, and contrary to our a priori hypothesis, SNB appears to be equivalent to morphine for transitional analgesia in this patient population. Future studies are needed to assess the benefits of other analgesic strategies for transitional analgesia in patients undergoing intracranial surgery. REFERENCES
1. Balakrishnan G, Raudzens P, Samra S, et al. A comparison of remifentanil and fentanyl in patients undergoing surgery for intracranial mass lesions. Anesth Analg 2000;91:1639. 2. Gelb AW, Salevsky F, Chung F, et al. Remifentanil with morphine transitional analgesia shortens neurological recovery compared to fentanyl for supratentorial craniotomy. Can J Anaesth 2003;50:946 52. 3. Guy J, Hindman BJ, Baker KZ, et al. Comparison of remifentanil and fentanyl in patients undergoing craniotomy for supratentorial space-occupying lesions. Anesthesiology 1997;86:514 24. 4. Gerlach K, Uhlig T, Huppe M, et al. Remifentanil-propofol versus sufentanil-propofol anaesthesia for supratentorial craniotomy: a randomized trial. Eur J Anaesth 2003;20:81320. 5. Nguyen A, Girard F, Boudreault D, et al. Scalp nerve blocks decreases the severity of pain following craniotomy. Anesth Analg 2001;93:1272 6. 6. Pinosky ML, Fishman RL, Reeves ST, et al. The effect of bupivacaine skull block on the hemodynamic response to craniotomy. Anesth Analg 1996;83:1256 61. 7. Magni G, Baisi F, Rosa I, et al. No difference in emergence time and early cognitive function between sevoflurane-fentanyl and propofol-remifentanil in patients undergoing craniotomy for supratentorial intracranial surgery. J Neurosurg Anesthesiol 2005;17:134 8. 8. Cafiero T, Burelli R, Latina P, Mastronardi P. Analgesic transition after remifentanil-based anesthesia in neurosurgery. A comparison of sufentanil and tramadol. Minerva Anesthesiol 2004;70:4552.

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