ABSTRACT INTRODUCTION. Gomaa Zohry 1, Hazem Hosny 1, Dalia Nabil 1, Mona T. El-Ghoneimy 2

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1 Gomaa Zohry et al. Lidocaine Infiltration versus Intravenous Fentanyl for Preventing the Hemodynamic Response to Pin Insertion in Craniotomy Patients: A Transcranial Doppler study Gomaa Zohry 1, Hazem Hosny 1, Dalia Nabil 1, Mona T. El-Ghoneimy 2 Departments of Anesthesia 1, Neurosurgery 2, Cairo University ABSTRACT Background: This study was designed to compare local anesthetic infiltration of the scalp with lidocaine to prior administration of intravenous fentanyl as methods of preventing hemodynamic alterations associated with pin insertion in craniotomy surgery. Methods: Thirty patients undergoing supratentorial tumor surgery were randomly allocated into two equal groups. Anesthesia was standardized in the two groups using propofol, fentanyl and atracurium for induction and sevoflurane-atracurium for maintenance. Ten minutes before application of pins, one group received local infiltration of the scalp with 2% lidocaine at the sites of pin insertion, while the other group received 1 μg/kg fentanyl intravenously. Heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), arterial blood gas (ABG) analysis and transcranial Doppler (TCD) evaluation of the cerebral blood flow velocity in the middle cerebral artery (CBFV MCA ) were done at baseline, just before pin insertion, and 1 and 5 minutes after pin insertion. Results: HR and MAP increased significantly after pin insertion in the fentanyl group at 1 and 5 minutes after application of the pins, while they increased only at 1 minute in the lidocaine group; the difference between the two groups at 1 and 5 minutes was statistically significant (P<0.01). CBFV MCA did not change significantly from before to after pin insertion in the lidocaine infiltration group, while it increased significantly in the fentanyl group relative to both before-pin values and to the lidocaine group (P<0.01). CVP and results of ABG analysis were comparable between the groups all through the study period. Conclusion: Following pin insertion in craniotomy patients, local anesthetic infiltration of the scalp with lidocaine 2% prevents hemodynamic alterations and increases in CBFV MCA significantly better than prior administration of intravenous fentanyl. (Egypt J. Neurol. Psychiat. Neurosurg., 2006, 43(1): 41-48) INTRODUCTION Pin-holder application for skull fixation in craniotomy patients is common in clinical practice. Pain resulting from pin insertion causes adverse hemodynamic reactions in the form of rise of heart rate and blood pressure. Many previous investigations have been carried out to compare various methods of preventing this unwanted response 1 5. Not only the arterial blood pressure rises, but also the cerebrospinal fluid pressure 2,6. These changes can be deleterious in patients with compromised intracranial compliance. Local anesthetic infiltration was shown to be superior to other methods for prevention of this hemodynamic response. However, to the best of our knowledge, no previous study applied transcranial Doppler (TCD) monitoring to compare local anesthetic infiltration with any other method of analgesia. 41

2 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 PATIENTS AND METHODS After approval of the local Ethics Committee and obtaining written informed consent, 30 ASA physical status I-II patients, aged years, were included in the study. All patients had supratentorial brain lesions and were scheduled for craniotomy in the supine position with the head elevated about 30. Exclusion criteria were metabolic, vascular, cardiac, renal hepatic or pulmonary disease. Patients with Glasgow Coma Scale (GCS) score less than 14 or those with a midline shift of more than 5 mm in the preoperative CT or MRI scan were also excluded from the study. On arrival to the operating room, routine monitors (ECG, SpO 2 and non-invasive blood pressure monitor) were attached to the patients, who were premedicated with 0.02 mg/kg midazolam intravenously. A double-lumen central venous catheter was inserted under local anesthesia into the right internal jugular vein. The radial artery of the non-dominant hand was cannulated with a 20G cannula under local anesthesia. Baseline hemodynamic parameters [heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP)] were recorded. An arterial blood sample was collected for analysis of baseline arterial blood gases (ABGs). Prior to induction of general anesthesia, the time-averaged mean cerebral blood flow velocity in the middle cerebral artery (CBFV MCA ) was measured using a 2-MHz pulsed portable transcranial Doppler (TCD) device (Multi-Dop-L, DWL, Sipplingen, Germany) with the probe fixed in place using a probe holder to ensure a constant insonation angle for subsequent readings. CBFV MCA was measured on the side opposite to the intracranial lesion in non-midline tumors and on the right side in midline tumors. The Doppler probe was placed over the zygomatic arch between the lateral margin of the orbit and the ear and directed toward the M 1 segment of the middle cerebral artery (MCA) at a depth of mm, depending on optimization and stability of the signal. All measurements were taken by the same investigator who was blinded to the technique of anesthesia. All patients received a fluid preload in the form of 500 ml Hetastarch solution, to ensure that the CVP is above 5 cm H 2 O. Anesthesia was induced with fentanyl (3 μg/kg) and propofol (1 2 mg/kg). Atracurium (0.5 mg/kg) was given to facilitate endotracheal intubation with a propersized cuffed endotracheal tube. Mechanical ventilation was adjusted to keep end-tidal CO 2 between mm Hg to ensure mild hyperventilation. Anesthesia was maintained by sevoflurane MAC in 100% oxygen and atracurium infusion at a rate of 0.5 mg/kg/h starting immediately after induction of anesthesia. Muscle relaxation was monitored using train-offour stimulation of the ulnar nerve to ensure absence of all four twitches. Patients were randomly divided into two equal groups (n = 15 each). Ten minutes before pin placement, patients in each group received a specific treatment according to group assignment. In group L, the scalp was infiltrated with 5 ml of lidocaine 2% with epinephrine 1:200,000 at each of the three sites of pin application, and patients received a 10-ml bolus of intravenous normal saline. In group F, the scalp was infiltrated with 5 ml of normal saline at each of the three sites of pin application, and patients received a 10-ml bolus of intravenous fentanyl, 1 μg/kg. Recorded parameters included HR, MAP, CVP, CBFV MCA, PaO 2 and PaCO 2 at baseline, just before pin-holder placement and 1 and 5 minutes after pin-holder placement. Statistical analysis: Data were expressed as mean (SD). Unrepeated measurements were compared between the groups using unpaired two-tailed Student s t-test. Repeated measurements were compared between the groups using analysis of variance (ANOVA) and post hoc Tukey s honest significant difference test. Incidences were compared using Fisher s exact test. P values < 0.05 were considered statistically significant. 42

3 Mona Talaat et al. RESULTS The two groups were comparable to each other as regards age, gender, weight, type of tumor, propofol induction dose and fentanyl induction dose (Table 1). All patients had low CVP at baseline, with no differences between the groups. Administration of the fluid preload raised CVP significantly (P<0.001) in both groups, with no significant difference between the groups till the end of the study. Both groups had comparable HR and MAP at baseline, but HR decreased significantly in the fentanyl group compared with the lidocaine group just before pin insertion (P<0.05), while MAP was comparable in the two groups at that time. One minute after application of pins, there was a significant (P<0.05) increase in HR and MAP in both groups relative to before-pin values; the rise was significantly higher in the fentanyl group (P<0.001) relative to the lidocaine group. Five minutes after pin insertion, HR and MAP returned to near before-pin values in the lidocaine group, while they remained significantly higher in the fentanyl group (Table 2). Regarding ABG analysis, PO 2 rose significantly (P<0.001) and PCO 2 decreased significantly (P<0.01) in both groups relative to baseline, with no significant differences between the two groups all through the study period (Table 3). Transcranial Doppler study demonstrated a significant reduction in CBFV MCA in both groups before pin placement relative to baseline, with no significant difference between the groups either at baseline or before pin placement. One minute after insertion of pins, there was a mild nonsignificant increase in CBFV MCA in the lidocaine group, and a larger significant increase in the fentanyl group relative to before-pin values (P<0.01) and relative to the lidocaine group (P<0.005). Five minutes after pin insertion, the significant increase in CBFV MCA was still persistent in the fentanyl group (Table 3, Figure 1). Table 1. Demographic and operative data [mean (SD), ratio, or number (%) of cases]. Group F Group L (n = 15) (n = 15) Age (year) 35 (7.4) 33 (4.8) Gender (M/F) 8/7 9/6 Weight (kg) 71 (5.2) 73 (5.9) Tumor Glioma 7 (46.7%) 6 (40%) Meningioma 5 (33.3%) 7 (46.7%)) Sellar-suprasellar mass 2 (13.3%) 1 (6.7%) Metastatic mass 1 (6.7%) 1 (6.7%) Total propofol dose (mg/kg) 1.7 (0.41) 1.7 (0.38) Total fentanyl dose (μg/kg) 3.1 (0.16) 3.0 (0.09) 43

4 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 Table 2. Hemodynamic data [mean (SD)]. Heart rate (beats/min) Mean arterial pressure (mmhg) Central venous pressure (cm H 2 O) Group F (n = 15) Group L (n = 15) Baseline 77 (6.4) 78 (5.9) Before pins 73 (6.7) 77 (5.0) 1 min after pins 92 (4.7)* 83 (2.8)* 5 min after pins 87 (4.6)* 80 (5.1) Baseline 95 (5.8) 96 (6.0) Before pins 93 (4.2) 95 (3.5) 1 min after pins 116 (4.2)* 103 (5.3)* 5 min after pins 110 (4.5)* 98 (4.3) Baseline 4.3 (2.63) 4.5 (2.17) Before pins 7.5 (1.43) 7.5 (1.78) 1 min after pins 7.6 (2.38) 7.9 (2.39) 5 min after pins 7.5 (2.43) 7.4 (2.04) *P < 0.05 relative to before-pin values in the same group P < 0.01 relative to lidocaine group. P < relative to baseline in the same group. Table 3. Arterial blood gas analysis and transcranial Doppler values [mean (SD)]. Group F (n = 15) Group L (n = 15) PCO 2 (mm Hg) Baseline 40.1 (1.74) 40.2 (2.25) Before pins 31.7 (1.82)* 31.8 (1.81)* 1 min after pins 32.3 (1.67)* 32.4 (2.22)* 5 min after pins 32.2 (1.52)* 32.0 (1.95)* PO 2 (mm Hg) Baseline 93 (2.9) 94 (4.0) Before pins 397 (22.2)* 393 (18.7)* 1 min after pins 401 (19.1)* 404 (19.0)* 5 min after pins 399 (23.5)* 395 (15.6)* CBFV MCA (cm/s) Baseline 71 (5.2) 72 (4.2) Before pins 59 (6.2)* 57 (6.3)* 1 min after pins 66 (7.0)* 60 (5.2)* 5 min after pins 64 (5.3)* 59 (6.1)* CBFV MCA = cerebral blood flow velocity in the middle cerebral artery. *P < 0.01 compared with baseline values in the same group. P < 0.01 compared with before-pin values. P < compared with lidocaine group. 44

5 CBFV MCA (cm/s) Mona Talaat et al. Fentanyl group Lidocaine group * * * * * * 50 Baseline Before pins 1 min after pins 5 min after pins Time of measurement Fig. (1): Cerebral blood flow velocity in the middle cerebral artery (CBFV MCA ; cm/s) in the two groups of the study. Values represent mean (SD). *P < 0.01 compared with baseline values in the same group. P < 0.01 compared with before-pin values. P < compared with lidocaine group. DISCUSSION The present study demonstrated that hemodynamic changes associated with pin insertion in patients undergoing craniotomy surgery can be ameliorated more efficiently by infiltration of the scalp with lidocaine 2% than by prior administration of intravenous fentanyl. Infiltration of the scalp with lidocaine was found to blunt more effectively the hemodynamic response and the rise in cerebrospinal fluid pressure than deepening the level of anesthesia with propofol or thiopentone, or premedicating the patient with intravenous fentanyl 2. Bupivacaine infiltration was found to have similar hemodynamic effects 7. Schaffranietz et al reported that lidocaine infiltration, but not alfentanil or propofol administration was successful in preventing hemodynamic effects of pin application 8. Combining intravenous fentanyl and local infiltration with lidocaine was reported to produce a better hemodynamic profile than lidocaine alone, although the latter was still more effective than intravenous fentanyl alone 9. Agarwal et al described a maximum attenuation of the hemodynamic response to pin placement when patients were premedicated with ketamine (0.5 mg/kg) and the scalp was infiltrated with lidocaine 1% 1. 45

6 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 Controversy existed about the use of other drugs to prevent the hemodynamic response to pin insertion. In one study 3, clonidine was reported to be effective in blunting hemodynamic responses to pin insertion, while in another study 6 it was reported to lack this effect. Alfentanil was reported to blunt the hemodynamic response to pin insertion as effectively as lidocaine 4, but its failure to prevent this response was also reported in another study 8. Target-controlled infusion of propofol/sufentanil was also reported to effectively prevent the rise in blood pressure in response to pin insertion, but it had the drawback of causing hypotension in the absence of noxious stimuli 5. Another study reported that sufentanil failed to prevent this hemodynamic response, regardless of the plasma concentration of the drug 10. Fentanyl was found to be effective in preventing the rise in blood pressure after pin insertion, but the required dose was relatively large (4.5 μg/kg) and resulted in bradycardia and/or hypotension that necessitated pharmacological treatment 11. Remifentanil was reported to decrease the changes in cerebral blood flow velocity in volunteers exposed to a noxious stimulus 12. It could be seen from the previous reports that local anesthetic infiltration of the scalp seems to be superior to other techniques in preventing the adverse hemodynamic response to pin insertion. While opioids and clonidine were sometimes shown to prevent this response, they can be associated with relative hemodynamic instability as compared with lidocaine infiltration. To the best of our knowledge, no other study examined the effects of pin application on cerebral blood flow velocity. Indeed, the more important parameter to consider is the cerebral blood flow (CBF) and cerebral blood volume (CBV) rather than flow velocity. However, although the absolute velocity of cerebral blood flow cannot be used as a quantitative indicator of the cerebral blood flow, it correlates well with the latter and can be used as an indicator of the trend of CBF in the same patient 13. We therefore consider the significant rise in the CBFV MCA an indication of a similar rise in the CBF in the current study. In order for the TCD study to be valid, diameters of the large cerebral vessels should remain almost constant throughout the study 14. In craniotomy patients, it was shown that changes in blood pressure as much as 30 (16) mm Hg and changes in end-tidal CO 2 as much as 14 (6) mmhg were not associated with significant changes in the diameter of large cerebral blood vessels 15. We therefore assumed that comparisons between TCD values before and after pin placement are valid in the present study, as changes in MAP and end-tidal CO 2 were within the range reported before. Another study demonstrated that application of the head-holder resulted in a significant increase in bispectral index (BIS) values, and that the degree of BIS increase was inversely related to the plasma concentration of sufentanil 10. Therefore, it can be reasonably stated that changes in CBFV MCA following pin insertion were primarily related to the associated changes in MAP and the probable activation of the brain following application of the noxious stimulus. TCD monitoring in the present study was not meant to quantify the effect of a particular agent on CBFV MCA, but rather to compare two techniques of analgesia in craniotomy patients to avoid the adverse hemodynamic events that accompany pin insertion. The rise of CBFV MCA that occurred with the use of fentanyl rather than lidocaine implies a concomitant rise in CBF and CBV, which should be avoided in craniotomy patients. We conclude that, in craniotomy patients, local infiltration of the scalp with lidocaine 2% at the sites of pin insertion attenuated pain-induced hemodynamic and CBFV MCA changes during pin application while prior administration of fentanyl (1 μg/kg) failed to achieve this effect. This effect can be of particular importance in patients with critically compromised intracranial compliance. Further studies are required to examine the efficacy of lidocaine infiltration of the scalp in this patient population. 46

7 Mona Talaat et al. REFERENCES 1. Agarwal A, Sinha PK, Pandey CM, et al. Effect of a subanesthetic dose of intravenous ketamine and/or local anesthetic infiltration on hemodynamic responses to skull-pin placement: a prospective, placebo-controlled, randomized, double-blind study. J Neurosurg Anesthesiol 2001; 13: Bayer-Berger MM, Ravussin P, Fankhauser H, et al. Effect of three pretreatment techniques on hemodynamic and CSFP responses to skull-pin head-holder application during thiopentone/ isoflurane or propofol anesthesia. J Neurosurg Anesthesiol 1989; 1: Costello TG, Cormack JR. Clonidine premedication decreases hemodynamic responses to pin head-holder application during craniotomy. Anesth Analg 1998; 86: Doblar DD, Lim YC, Baykan N, et al. A comparison of alfentanil, esmolol, lidocaine, and thiopental sodium on the hemodynamic response to insertion of headrest skull pins. J Clin Anesth 1996; 8: Hans P, Coussaert E, Cantraine F, et al. Effects of target-controlled anesthesia with propofol and sufentanil on the hemodynamic response to Mayfield head holder application. Acta Anaesthesiol Belg 1998; 49: Favre JB, Gardaz JP, Ravussin P. Effect of clonidine on ICP and on the hemodynamic responses to nociceptive stimuli in patients with brain tumors. J Neurosurg Anesthesiol 1995; 7: Mathieu D, Beaudry M, Martin R, et al. Effect of the local anesthetic agent bupivacaine prior to application of the skull-pin holder for craniotomies. J Neurosurg 2003; 98: Schaffranietz L, Ruffert H, Trantakis C, et al. [Effect of local anesthetics on hemodynamic effects during Mayfield skull clamp fixation in neurosurgery using total intravenous anesthesia]. Anaesthesiol Reanim 1999; 24: Ozkose Z, Yardim S, Yurtlu S, et al. The effects of intravenous fentanyl and lidocaine infiltration on the hemodynamic response to skull pin placement. Neurosurg Rev 2001; 24: Hans P, Brichant JF, Dewandre PY, et al. Effects of two calculated plasma sufentanil concentrations on the hemodynamic and bispectral index responses to Mayfield head holder application. J Neurosurg Anesthesiol 1999; 11: Jamali S, Archer D, Ravussin P, et al. The effect of skull-pin insertion on cerebrospinal fluid pressure and cerebral perfusion pressure: influence of sufentanil and fentanyl. Anesth Analg 1997; 84: Lorenz IH, Kolbitsch C, Hinteregger M, et al. Remifentanil and nitrous oxide reduce changes in cerebral blood flow velocity in the middle cerebral artery caused by pain. Br J Anaesth 2003; 90: Bishop CC, Powell S, Rutt D, et al. Transcranial Doppler measurement of middle cerebral artery blood flow velocity: a validation study. Stroke 1986; 17: Aaslid R, Markwalder TM, Nornes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg 1982; 57: Giller CA, Bowman G, Dyer H, et al. Cerebral arterial diameters during changes in blood pressure and carbon dioxide during craniotomy. Neurosurgery 1993; 32:

8 Egypt J. Neurol. Psychiat. Neurosurg. Vol. 43 (1) Jan 2006 الملخص العربي التغيراث الذيىاميكيت للذورة الذمويت لوضع مسامير الرأس في حاالث عملياث فتح الذماغ بيه مقاروت الحقه الموضعي بفروة الرأس لعقار الليذوكان مع عقار الفىتاويل عبر الحقه الوريذى: دراست الذوبلر عبر الذماغ