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Year : 2018  |  Volume : 12  |  Issue : 1  |  Page : 213-217  

Evaluation of the hemodynamic response of intravenous clonidine versus ropivacaine scalp block to insertion of scalp pins in neurosurgical patients

Department of Anesthesiology, Bangalore Medical College and Research Institute, Bengaluru, Karnataka, India

Date of Web Publication9-Mar-2018

Correspondence Address:
Dr. Saraswathi Nagappa
Department of Anesthesiology, Bangalore Medical College and Research Institute, Bengaluru, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0259-1162.194572

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Background: The application of the skull-pin head-holder, used to stabilize the head during neurosurgical procedures, produces an intense nociceptive stimulus and results in abrupt increases in blood pressure and cerebral blood flow under general anesthesia. Different anesthetic and pharmacologic techniques, including local anesthetics, narcotics, antihypertensives, and deepening of anesthesia with inhalation anesthetics, have been used to blunt this deleterious effect with variable success. Aim: To compare the analgesic and hemodynamic effects of ropivacaine scalp block, and intravenous (IV) clonidine in attenuating the hemodynamic response to the scalp pin insertion in neurosurgical patients. Settings and Design: A comparative two group's clinical study of 64 patients undergoing elective craniotomy in Department of Anaesthesiology, Bangalore Medical College and Research Institute. Methodology: Sixty-four patients were allocated into any one of two groups of 32 patients each, by means of computer-generated randomization: (1) Group S: Patients receiving scalp block with injected ropivacaine 0.25% 30 ml. (2) Group C: Patients receiving 2 μg/kg IV clonidine. Statistical Methods: Descriptive and inferential statistical analysis has been carried out in the present study. Results on continuous measurements are presented on mean ± standard deviation (minimum–maximum) and results on categorical measurements are presented in number (%). Significance is assessed at 5% level of significance. Results: Increase in heart rate and blood pressure during pin insertion was attenuated by clonidine hydrochloride (P < 0.001). The number of patients who required more fentanyl and propofol to stabilize the hypertensive response were more in control group than clonidine group. Conclusion: IV clonidine maximally attenuated the hemodynamic response to application of head pins in a dose of 2 μg/kg compared to ropivacaine scalp block, thus maintaining intracranial pressure for neurosurgical anesthesia.

Keywords: α2-agonists, clonidine hydrochloride, craniotomy, hemodynamic response, scalp blocks

How to cite this article:
Nagappa S, Kalappa S, Sridhara RB. Evaluation of the hemodynamic response of intravenous clonidine versus ropivacaine scalp block to insertion of scalp pins in neurosurgical patients. Anesth Essays Res 2018;12:213-7

How to cite this URL:
Nagappa S, Kalappa S, Sridhara RB. Evaluation of the hemodynamic response of intravenous clonidine versus ropivacaine scalp block to insertion of scalp pins in neurosurgical patients. Anesth Essays Res [serial online] 2018 [cited 2019 Jun 16];12:213-7. Available from:

   Introduction Top

Anesthesia for craniotomy requires special considerations. The brain is enclosed in a rigid skull and at the same time, being a vascular organ presents potential for massive perioperative hemorrhage and increased intracranial pressure (ICP). Maintenance of adequate blood flow to the brain is of fundamental importance in neuroanesthesia[1] because of tolerance of the brain to interruption of substrate delivery is minimal. Increased ICP in patients with mass lesions is due to poor volume compensation and intracranial compliance. As the ICP depends on mean arterial pressure (MAP), it is important to maintain the ICP throughout the surgery by controlling the MAP. Not only the arterial blood pressure rises but also the cerebrospinal fluid pressure.[2],[3],[4] These changes can be deleterious in patients with compromised intracranial compliance. Different methods including local anesthetic infiltrations,[5],[6],[7],[8] skull blocks, and narcotics and deepening of anesthesia with inhalation and intravenous (IV) anesthetics have been used to blunt this deleterious effect with variable success.[5] Although the onset of analgesia is rapid, no additional increase in the depth of anesthesia and effective attenuation of hemodynamic perturbations and small volume of the drug required are claimed as the advantages for the infiltration technique, it is not without disadvantages. It is effective only if a couple of minutes are allowed to elapse between infiltrations and pinning. The infiltration is so localized that a reapplication at a different site requires infiltration again. Reapplication of pins is not an uncommon event in neurosurgical practice. The multiple injections required increases the risk of needle stick injury.

Clonidine is an antihypertensive agent that reduces sympathetic outflow via α2-adrenergic receptor stimulation.[9],[10] α2 adrenergic receptors are distributed widely within and outside the central nervous system (CNS), mostly in the region of pons and medulla which regulates the transmission of sympathetic nervous system stimulation from higher centers to the periphery. Presynaptic α2-receptors activation inhibits the release of norepinephrine. Whereas α2-adrenoceptors situated postsynaptic in the dorsal horn and on vascular smooth muscle when stimulated prevents nociceptive signal transmission and causes vasoconstriction, respectively.[11],[12],[13] Stimulation of α2 receptors by clonidine in the CNS has a role on sedation for which clonidine is widely used as an adjunct to anesthesia and pain medicine.[14] Clonidine reduces sympathetic tone and the release of norepinephrine from nerve terminals.[15] During general anesthesia, clonidine reportedly enhances intraoperative circulatory stability by reducing catecholamine levels.[16] Therefore, the use of clonidine during surgery has been proposed as a way of improving hemodynamics, decreasing both the ICP and anesthetic requirements. We conducted this trial to compare the analgesic and hemodynamic effects of ropivacaine and IV clonidine in attenuating the hemodynamic response to the scalp pin insertion in neurosurgical patients.

   Methodology Top

The study design was a prospective, double-blinded, randomized trial on patients undergoing elective craniotomy in Bangalore Medical College and Research Institute conducted over 1 year. Witnessed informed consent was obtained from all patients before surgery by the anesthesiologist, 64 patients were included in the study. They were allocated into any one of two groups of 32 patients each, by means of computer-generated randomization:

  • Group S: Patients received scalp block with injection ropivacaine 0.25% 30 ml
  • Group C: Patients received 2 μg/kg IV clonidine.

Before induction of general anesthesia, standard monitors such as electrocardiography and pulse oximetry probe were connected. The radial artery on the nondominant hand was cannulated under local anesthesia with a 20-gauge cannula for continuous blood pressure monitoring. The baseline heart rate (HR) and arterial blood pressure were recorded. Patient in the Group C (clonidine group) was given a bolus dose of clonidine (2 μg/kg) as an infusion over a period of 10 min, before induction of anesthesia. Induction of anesthesia was achieved with a standard induction protocol for all patients with propofol (2 mg/kg), fentanyl (2 μg/kg), and vecuronium (0.15 mg/kg). After endotracheal intubation, anesthesia was maintained with 0.8 minimal alveolar concentration of isoflurane in 50% O2:air. In the patients assigned to Group S (scalp block group), bilateral ropivacaine skull block was performed with 30 ml of 0.5% ropivacaine - 15 ml on each side by the principal investigator, as described by Pinosky et al. under sterile precautions.[15] Bradycardia was defined as HR <50 bpm, tachycardia as a >20% increase from baseline in HR, hypertension as a >20% increase from baseline in MAP, and hypotension as <20% decrease from baseline in MAP. Bradycardia was treated by administration of atropine 0.6 mg.

The person who monitored the patients was blinded for both the techniques. Hypotension was treated by administration of 5 mg of ephedrine. Refractory or persistent hypotension was defined as hypotension requiring more than three boluses of ephedrine and more than 500 ml of crystalloid. In both the groups, any rise in the HR or MAP, more than 20% of baseline was treated immediately in two successive steps. The second step was followed only if the first step failed to control the rise in MAP and HR, respectively.

  • Step 1: Single bolus administration of fentanyl 1 μg/kg
  • Step 2: Bolus injections of propofol, 1 mg/kg.

Statistical software

The statistical software, namely, SAS 9.2 (SAS Institute, Cary, NC, USA), SPSS 15.0 (SPSS version 15.0 IBM Corp, Armonk, NY), Stata 10.1 (Statacorp LP, 4905 Lakeway Drive, College Station, Texas, USA), MedCalc 9.0.1 (American Statistical Association, Acacialaan 22, 8400 Ostend, Belgium), Systat 12.0 (Systat Software, San Jose, CA 95131, USA), and R environment version 2.11.1 were used for the analysis of the data, and Microsoft Word and Excel have been used to generate graphs, tables, etc.

Student's t-test (two-tailed, independent) has been used to find the significance of study parameters on continuous scale between two groups (intergroup analysis) on metric parameters.

Chi-square/Fisher's exact test has been used to find the significance of study parameters on categorical scale between two or more groups.

   Results Top

The two groups were comparable to each other as regards age, gender, and weight [Table 1] and [Figure 1]. The comparison of baseline hemodynamic parameters was statistically insignificant (P > 0.05) between the two groups. During pin application, i.e., 0 min (0.001) and after application of pins at 1 min (<0.001), 2 min (0.011), and 3 min (0.036), there was a significant increase in HR in both groups relative to before-pin values; the rise was significantly higher in the scalp block group (P< 0.001) relative to the clonidine group. Significant rise (P< 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP in scalp block during 0, 1, 2, 3, 4, and 5 min compared to clonidine group. Five minutes after pin insertion, HR, SBP, DBP, and MAP returned to near before-pin values in the clonidine group while they remained significantly higher in the scalp block group [Table 2], [Table 3] and [Figure 2], reflecting that the analgesia obtained with clonidine was of better quality than that achieved with scalp block.
Table 1: Baseline information of patients in two groups studied

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Figure 1: Gender distribution

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Table 2: Comparison of Heart rate (beats/min) of patients in two groups studied

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Table 3: Comparison of MAP (mm Hg) of patients in two groups studied

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Figure 2: Comparison of MAP (mmHg) of patients in two groups studied

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Additional bolus of fentanyl was required more for scalp block group (18.8) compared to clonidine group (6.3) and combined fentanyl, and propofol requirement was also greater in the control group (28.1) compared to clonidine group (0). Only one case in control scalp group had reapplication of pins, which required additional injection fentanyl 2 μg/kg [Figure 3].
Figure 3: Percentage of requirement of drugs

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   Discussion Top

Clonidine appears to possess many properties that make it an appealing adjunct to the intraoperative management of neurosurgical patients.[3] α2-agonists are a novel class of drugs with mechanisms of action that differ from other commonly used anesthetic drugs. They have neuroprotective, cardioprotective, and sedative effects. These unique characteristics make them potentially useful during neuroanesthesia.[1],[9] Clonidine prevents fluctuation of hemodynamics throughout the entire perioperative period, which is very important in neurosurgical patients.[11] By stimulating α2-receptors, clonidine decreases total peripheral resistance, renal vascular resistance, HR, and blood pressure.[1],[9],[10] This agent also decreases cerebral electrical activity and the cortical response to sensory input, which may partially explain the decrease in anesthetic requirements associated with clonidine administration. In neurosurgical patient's clonidine lowers glucose, aldosterone, and plasma cortisol concentrations and does not affect ICP as measured from cerebrospinal fluid pressure.[11] Furthermore, clonidine decreases sympathetic overactivity in head-injured patients.[12] Control of hemodynamic parameters during neurosurgical procedures is of great concern to the neuroanesthesiologist whose goal includes ensuring optimal cerebral perfusion pressure. α2-agonists, through their central sympatholytic action, can induce hypothermia and inhibit the shivering response to hypothermia. Shivering frequently limits the effectiveness of hypothermia measures, and α2-agonists may be useful in the management of hypothermia for neuroprotection or ICP control in addition to endotracheal intubation and surgical incision, head-holder insertion is an intense nociceptive stimulus that dramatically increases MAP and HR. The head-holder device consists of a C-shaped metal clamp with three sharpened metal pins triangularly arranged to fit on the skull. In most institutions, the pins are tightened until they press into the skull of the anesthetized patient with eighty pounds of pressure.[10] Unlike stimulation by endotracheal intubation, which varies with the skill of the anesthesiologist, type of endotracheal tube, and anatomy of the larynx, the placement of the head-holder is a more reproducible stimulus each time it is applied. This 'uniform' stimulus should be blunted in neurosurgical patients to avoid unwanted increases in blood pressure, HR, and ICP.

The present randomized, double-blind study demonstrated that hemodynamic changes associated with pin insertion in patients undergoing craniotomy can be ameliorated more efficiently when clonidine was used as IV premedication. Both the groups did not differ with respect to age, weight, and sex. All preoperative baseline hemodynamic variables were almost identical in both groups (P > 0.05). Gaumann et al. noted that patients treated with clonidine had lower values of MAP than patients with placebo.[17] Oral clonidine premedication in craniotomy, a study conducted by Traill and Gilliesnoted that in clonidine group lower SBP on arrival in the operative room, preinduction, and postintubation than control group.[18] IV route was chosen to provide exact drug dosing and a gap of 10–15 min between administration of drug and induction of patients was chosen because onset of action of IV clonidine is 2–28 min and an average of 15 min was taken.

Favre et al.[4] administered clonidine 3 μg/kg 10 min before surgery. The dose, route of administration, and time interval were similar to our study. In our study, the MAP showed an increase during pin head-holder application in control group which was highly significant (0.001). On comparison between the two groups at various intervals, we found that there was a significant difference in HR between the two groups. The difference in HR between the two groups was highly significant (P< 0.001) at P 1. There were no cases of bradycardia reported in either group. Jellish et al. in their study show that baseline HR was lower in patients who received clonidine.[10] Endotracheal intubation is associated with significant increases of arterial pressure, HR; clonidine attenuates the sympathoadrenal stimulation during tracheal intubation effectively. This was observed in our study also as the decrease in HR was maintained after induction in the Group C, but not in the Group S. Costello and Cormack suggested that oral clonidine (3 μg/kg, 90 min before induction) is effective in controlling the increase in MAP (P = 0.03) resulting from pin head-holder application.[19]

There have been studies using dexmedetomidine, the other potent α2-agonist. Uyar et al. have shown that single bolus of dexmedetomidine before induction of anesthesia attenuated the hemodynamic and neuroendocrinal response to skull pin insertion as compared to that of placebo.[20] Dawlatly et al. showed that the use of a small dose of dexmedetomidine (0.25 mcg/kg by infusion) has resulted in obtunding the hemodynamic responses to skull pin placement similar to lidocaine infiltration.[21]

Duration of action of dexmedetomidine being less than clonidine, we chose to study the latter drug to extend its hemodynamic obtunding effect into the intraoperative period. Clonidine appears to possess many properties that make it an appealing adjunct to the intraoperative management of neurosurgical patients.[10]

Our study showed that those patients with only scalp block required another drug to stabilize the hypertensive response during pin head-holder application, also scalp block procedure involves multiple injection and increase in operating room (OR) time.


  1. No patients with Glasgow Coma Scale below 15 were included in this study, and hence whether either of these techniques could have had a distinct advantage over the other in those with severely raised ICP could not be addressed in our study
  2. Direct estimation of ICP or the increase in ICP as a response to pinning which would probably be the gold standard was not measured. Only the hemodynamic responses were studied
  3. Difficult to monitor postoperative sedation score in clonidine group in craniotomy patients
  4. Future research direction would be interesting to compare the hemodynamic response to pin insertion in patients with borderline cardiovascular function, elderly patients, and those with severely elevated ICP with both the techniques. It would also be interesting to follow-up these patients throughout the procedure to compare the analgesic requirement, hemodynamic stability, and time taken for emergence among both the groups.

   Conclusion Top

We can state that during craniotomy clonidine maximally attenuated the hemodynamic response to application of head pins compared to ropivacaine scalp block in neurosurgical patients. Clonidine also reduced mean propofol and fentanyl requirements intraoperatively. There were no adverse effects observed in both the groups.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Makwama DS, Thakkar JM, Majmudar R, Shnodhi A, Malviya G, Patel BM. Clonidine premedication decreases hemodynamic responses to pin head-holder application during craniotomy. Asian Pac J Health Sci 2015;2:57-61.  Back to cited text no. 1
Zohry G, Hosny H, Nabil D, El-Ghoneimy MT. Lidocaine infiltration versus intravenous fentanyl for preventing the hemodynamic response to pin insertion in craniotomy patients: A transcranial doppler study. Egypt J Neurol PsychiatNeurosurg 2006;43:41-7.  Back to cited text no. 2
Bayer-Berger MM, Ravussin P, Fankhauser H, Freeman J. 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;1:227-32.  Back to cited text no. 3
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;7:159-67.  Back to cited text no. 4
Dhanasekaran R, Prashath PN, Selvi T. A prospective randomized controlled study to assess the efficacy of gabapentin in attenuating the haemodynamic responses during skull pin insertion in patients undergoing elective craniotomy. IOSR J Dent Med Sci 2015;14:55-63.  Back to cited text no. 5
Levin R, Hesselvik JF, Kourtopoulos H, Vavruch L. Local anesthesia prevents hypertension following application of the Mayfield skull-pin head holder. Acta Anaesthesiol Scand 1989;33:277-9.  Back to cited text no. 6
Mathieu D, Beaudry M, Martin R, McLelland H, Robert B, Kenny B. Effect of the local anesthetic agent bupivacaine prior to application of the skull-pin holder for craniotomies. J Neurosurg 2003;98:1194-7.  Back to cited text no. 7
Geze S, Yilmaz AA, Tuzuner F. The effect of scalp block and local infiltration on the haemodynamic and stress response to skull-pin placement for craniotomy. Eur J Anaesthesiol 2009;26:298-303.  Back to cited text no. 8
Dash SK, Gosayi KS, Parikh HG, Kondwikar B. Effect of clonidine, by infiltration and by intravenous route, on scalp block for supratentorial craniotomy. S Afr J Anaesthesiol Analg 2010;16:13-21.  Back to cited text no. 9
Jellish WS, Theard MA, Cheng MA, Leonetti JP, Crowder CM, Tempelhoff R. The effects of clonidine premedication and scalp infiltration of lidocaine on hemodynamic responses to laryngoscopy and skull pin head-holder insertion during skull base procedures. Skull Base 2001;11:169-76.  Back to cited text no. 10
Rifat Chowdhury MM, Islam MS, Bhowmick DK, Kamal MM, Akhtaruzzaman AK. Effects of clonidine on hemodynamic response and dural tightness in patients with supratentorial space occupying lesion undergoing craniotomy – A placebo controlled comparative study. Anaesth Pain Intensive Care 2015;19:233-9.  Back to cited text no. 11
Civantos Calzada B, Aleixandre de Artiñano A. Alpha-adrenoceptor subtypes. Pharmacol Res 2001;44:195-208.  Back to cited text no. 12
Scheinin M, Pihlavisis M. Molecular pharmacology of α2 adenoreceptor agonists. In: Scholz J, Tonner PH, editors. Bailliere's Best Practice and Research: Clinical Anesthesiology α2-Adenoreceptor Agonists in Anaesthesia and Intensive Care. London: Bailliere Tindall; 2000. p. 247-60.  Back to cited text no. 13
Kamibayashi T, Maze M. Clinical uses of alpha2 -adrenergic agonists. Anesthesiology 2000;93:1345-9.  Back to cited text no. 14
Pinosky ML, Fishman RL, Reeves ST, Harvey SC, Patel S, Palesch Y, et al. The effect of bupivacaine skull block on the hemodynamic response to craniotomy. Anesthesia and Analgesia 1996;83:1256-61.  Back to cited text no. 15
Morgan GE, Mikhail MS Jr., Murray MJ. Clinical Anesthesiology. 5th ed. New York: McGraw-Hill; 2013. p. 245.  Back to cited text no. 16
Gaumann DM, Tassonyi E, Rivest RW, Fathi M, Reverdin AF. Cardiovascular and endocrine effects of clonidine premedication in neurosurgical patients. Can J Anaesth 1991;38:837-43.  Back to cited text no. 17
Traill R, Gillies R. Clonidine premedication for craniotomy: Effects on blood pressure and thiopentone dosage. J Neurosurg Anesthesiol 1993;5:171-7.  Back to cited text no. 18
Costello TG, Cormack JR. Clonidine premedication decreases hemodynamic responses to pin head-holder. Anesthesiology 1987;67:3-10.  Back to cited text no. 19
Uyar AS, Yagmurdur H, Fidan Y, Topkaya C, Basar H. Dexmedetomidine attenuates the hemodynamic and neuroendocrinal responses to skull-pin head-holder application during craniotomy. J Neurosurg Anesthesiol 2008;20:174-9.  Back to cited text no. 20
Dawlatly AB, Abdullah K, Watidy SA, Jamjoom Z, Murshid WR, Delvi B. Effect of small dose intravenous dexmedetomidine and/or local anaesthetic infiltration on haemodynamic responses to skull pin placement. Pan Arab J Neurosurg 2006;10:29-33.  Back to cited text no. 21


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1], [Table 2], [Table 3]


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