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Year : 2014  |  Volume : 8  |  Issue : 2  |  Page : 187-191  

Preemptive analgesia of oral clonidine during subarachnoid block for laparoscopic gynecological procedures: A prospective study

1 Department of Anaesthesiology and Critical Care, N.S.C.B. Subharti Medical College, Swami Vivekananda Subharti University, Subharti Puram, Meerut, Uttar Pradesh, India
2 Department of Radio-diagnosis, Imaging and Interventional Radiology, N.S.C.B. Subharti Medical College, Swami Vivekananda Subharti University, Subharti Puram, Meerut, Uttar Pradesh, India

Date of Web Publication16-Jun-2014

Correspondence Address:
Prof. Kumkum Gupta
108, Chanakyapuri, Shastri Nagar, Meerut - 250 004, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0259-1162.134498

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Background: Preemptive analgesia is known modality to control the peri-operative pain. The present study was aimed to evaluate the effects of oral clonidine on subarachnoid block characteristics, hemodynamic changes, sedation and respiratory efficiency in patients undergoing laparoscopic gynecological procedures.
Patients and Methods: A total of 64 adult consenting females of American Society of Anesthesiologist physical status I and II were randomized double blindly into two groups of 32 patients each. Patients in the clonidine group received oral clonidine (100 μg) and patients of the control group received placebo capsule, 90 min before subarachnoid block with 0.5% hyperbaric bupivacaine (3.5 ml). The onset of sensory and motor block, maximum cephalic sensory level and regression times of sensory and motor blockade were assessed. Intra-operative hemodynamic changes, respiratory efficiency, shoulder pain and sedation score were recorded. The other side-effects, if any were noted and managed.
Results: The onset of sensory blockade was earlier in patients of clonidine group with prolonged duration of analgesia (216.4 ± 23.3 min vs. 165.8 ± 37.2 min, P < 0.05), but no significant difference was observed on motor blockade between groups. The hemodynamic parameters and respiratory efficiency were maintained within physiological limits in patients of clonidine group and no patient experienced shoulder pain. The Ramsey sedation score was 2.96 ± 0.75. In the control group, 17 patients experienced shoulder pain, which was effectively managed with small doses of ketamine and 15 patients required midazolam for anxiety.
Conclusion: Premedication with oral clonidine (100 μg) has enhanced the onset and prolonged the duration of spinal analgesia, provided sedation with no respiratory depression. The hemodynamic parameters remained stabilized during the pneumoperitoneum.

Keywords: Bupivacaine, clonidine, laparoscopic gynecological procedures, subarachnoid block

How to cite this article:
Gupta K, Singh I, Singh VP, Gupta PK, Tiwari V. Preemptive analgesia of oral clonidine during subarachnoid block for laparoscopic gynecological procedures: A prospective study. Anesth Essays Res 2014;8:187-91

How to cite this URL:
Gupta K, Singh I, Singh VP, Gupta PK, Tiwari V. Preemptive analgesia of oral clonidine during subarachnoid block for laparoscopic gynecological procedures: A prospective study. Anesth Essays Res [serial online] 2014 [cited 2022 Sep 25];8:187-91. Available from:

   Introduction Top

Laparoscopic gynecological procedures are advantageous due to reduction of post-operative pain, better cosmetic results and early return of normal activities. Subarachnoid block is a common technique for gynecological laparoscopic procedures, but this approach requires a relaxed and co-operative patient. [1] Many techniques and drug regimens, with partial or greater success have been tried from time to time to eliminate the anxiety and to prolong the post-operative analgesia during regional anesthesia. The adjuvants from different pharmacological classes of drugs have been studied for prolonging the duration of spinal anesthesia through intrathecal route.

Preemptive analgesia is more effective to control the peri-operative pain because it decreases the intra-operative stress response by reducing the nociceptive transmission of stimuli. Clonidine, an α2 adrenergic agonist, activates the receptors in the brain and spinal cord, thus decreases the sympathetic outflow, causing sedation, analgesia, hypotension and bradycardia, clonidine is widely used intrathecally or intravenously to prolong the duration of spinal anesthesia without any adverse effects. [2],[3] Several studies have documented that oral clonidine premedication reduced the peri-operative discomfort of pneumoperitoneum without risk of respiratory depression and awareness during laparoscopic procedures conducted under subarachnoid blockade. [4],[5]

The present study was aimed to evaluate the efficacy of pre-emptive analgesia of oral clonidine premedication on sensory and motor block characteristics, hemodynamic changes, respiratory efficiency, shoulder pain and sedation during laparoscopic gynecological surgery conducted under subarachnoid block.

   Patients and Methods Top

After approval of Institutional Ethical Committee, written informed consent was obtained. Totally 64 adult female patients of American Society of Anesthesiologist (ASA) I and II, aged 25-45 years with body weight 50-75 kg and height 145-165 cm, scheduled for laparoscopic gynecological surgery under subarachnoid block from October 2012 to November 2013 were enrolled for this prospective double-blind randomized control study. Patients with a history of severe cardiac or pulmonary diseases, hepatic or renal dysfunction, chronic pain or daily intake of analgesics, endocrinal or metabolic disorder and deformity of the spinal column, coagulation disorder, allergy to local anesthetic amides, cutaneous infection at the site of lumbar puncture or refusal to technique were excluded from the study. Patients were explained during the pre-operative assessment that any pain, anxiety or discomfort, during surgery would be treated effectively.

The patients were randomized, according to computer generated number, into two treatment groups of 32 patients each. Patients in the clonidine group received oral clonidine (100 μg) and patients of the control group received placebo capsule as premedication with a sip of water 90 min before the establishment of subarachnoid blockade with 3.5 ml of 0.5% hyperbaric bupivacaine. The patients and the Anesthesiologist were blinded to the randomization schedule. All patients were pre-medicated with ondansetron 4 mg and metoclopramide 10 mg intravenously.

On arrival to operation-theater, routine monitors of heart rate, electrocardiogram, pulse oximetry (oxygen saturation [SpO 2 ]) and systemic arterial blood pressure were attached for continuous monitoring. All patients were pre-hydrated with 15 ml/kg Ringer lactate solution before initiation of the subarachnoid block. Under all aseptic condition, the subarachnoid block was established with an intrathecal injection of 3.5 ml of 0.5% hyperbaric bupivacaine in a sitting position at the L2-3 or L3-4 interspace through midline approach using a 25 G Quincke spinal needle. The sensory block was assessed by pinprick method at 2 min intervals until the maximum level of sensory block was achieved. The motor blockade of lower limbs were evaluated by modified Bromage scale (0-3): (0) Full movement, no power impairment, (1) Unable to raise extended leg at the hip, but able to flex knees, (2) Unable to flex the knees (3) No movements. The surgical anesthesia was considered effective when at least T10 dermatome level was anesthetized.

The patients were breathing instituted oxygen supplementation at the rate of 5 L/min via a face mask throughout the laparoscopic gynecological procedure. Pneumoperitoneum was established with low pressure carbon dioxide of 10 mm Hg at a flow rate of 1 L/min.

The onset time of sensory and motor blockade at T10 dermatome, maximum cephalad dermatome level of sensory block, the two dermatome regression time to reach S1 sensory level and time taken to achieve complete recovery from motor blockade were assessed. Post-operatively the sensory and motor block levels were assessed at 15 min intervals until normal sensation returned. Total duration of analgesia was defined as time from administration of subarachnoid block until first complaint of pain. Injection diclofenac 75 mg intramuscular was used as rescue analgesic.

The systemic arterial blood pressure, heart rate, pulse oximetry, electrocardiography and end tidal carbon dioxide were recorded at base line, after subarachnoid block at 3 min interval until 15 min and then at every 5 min interval until the end of surgery and thereafter at every 30 min in the post-operative unit for next 3 h. For the present study, hypotension was defined as systolic blood pressure of <100 mm Hg and was treated primarily by increasing the intravenous crystalloid infusion rate and additionally with vasoactive drugs, if required. Bradycardia was defined as heart rate <60 beats/min and was treated with intravenous atropine.

The level of sedation was evaluated using Ramsey sedation score (RSS): (1) Patient anxious, agitated or restless, (2) Patient co-operative, oriented and tranquil alert, (3) Patient responds to commands, (4) Asleep but with brisk response, (5) Asleep with sluggish response, (6) Asleep with no response. The sedation score was evaluated every 10 min, considering the time of giving the premedication as zero. Duration of pneumoperitoneum was kept minimal. Intra-operative anxiety was treated with midazolam 2 mg. The ketamine 0.25 mg/kg was given intravenously for shoulder pain due to pneumoperitoneum. Intra-operatively any analgesic requirement, respiratory efficiency (defined as respiratory rate <10 breaths/min or pulse oximetry value of less than 94%), shivering, nausea and vomiting or any drug induced side effects were also recorded and managed promptly. An Anesthesiologist blinded to the study protocol, documented all the parameters.

Preliminary sample size was based on initial pilot observations, indicated that approximately 25-27 patients should be included in each group, to ensure power 0.80 for detecting clinically meaningful 20% difference in sensory regression of two dermatomes. Assuming a 5% dropout rate, the final sample size was set at 64 patients for better validation of results. The recorded data are presented in tabulated form as mean ± standard deviation statistical analysis was done using StatGraphics Centurion (Statpoint Technologies Inc). The demographic data for categorical variables were compared using Chi-square and statistical significance in mean difference was done by using Student's t-test. P < 0.05 was considered to be statistically significant.

   Results Top

The study protocol was successfully completed on all 64 female patients and all patients were co-operative fully with subsequent assessment. The demographic profile for age, weight, height, ASA classification, duration of pneumoperitoneum and laparoscopic gynecological procedure time were comparable between the groups [Table 1].
Table 1: Demographic profile of patients

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Onset of sensory analgesia at T10 dermatome was faster in patients of clonidine group (3.26 ± 1.13 min) when compared to the control group (3.58 ± 1.67 min) but with no statistical difference. Maximum cephalad level of sensory block (T 5.6 ± 0.7 vs. T 6.8 ± 0.4, P < 0.05) was higher in patients of clonidine group with statistically significant difference. The time required for two segment regressions and mean duration of sensory analgesia was significantly prolonged in patients of clonidine group (216.4 ± 23.3 min vs. 165.8 ± 37.2 min in the control group, P < 0.001). The onset and duration of motor blockade was comparable between the groups but of shorter duration as compared to sensory analgesia [Table 2] and [Figure 1].
Figure 1: Difference of subarachnoid block characteristics between groups

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Table 2: Sensory and motor blockade characteristics

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The base line hemodynamic parameters of heart rate and systemic blood pressure were comparable between the groups. Intra-operatively there was a clinically and statistically significant decrease in mean values of heart rate in patients of clonidine group and persisted to be lower. Transient hypotension was recorded in eight patients of clonidine group, which was treated effectively with volume expansion and if required, one bolus dose of 6 mg mephentermine. None of them required continuous pharmacological support. During the creation of pneumoperitoneum, the hemodynamic parameters showed 18.73% increase from baseline in patients of the control group while patients of clonidine group remained hemodynamically stabilized. No patient needed atropine.

The maximum mean RSS were higher (2.96 ± 0.75) in patients of clonidine group and achieved after 120 min of oral clonidine, while it was less than 2 in patients of the control group. Fifteen anxious patients of the control group needed intravenous midazolam and 17 patients complained of shoulder pain which was effectively treated with small doses of intravenous ketamine while all other patients were comfortable throughout the laparoscopic procedure.

The end tidal carbon dioxide increased over the first 10 min from 32.56 ± 3.28 to 36.67 ± 5.8 mm Hg and declined after deflation. All other observed changes were within physiological limits and SpO 2 levels were comparable between groups. Intra-operative shivering was observed in seven patients of the control group while no patients of clonidine group showed shivering. Only five patients have complained of nausea and vomiting during the study which was treated with intravenous ondansetron. The bowel recovery was not altered. None of the patient complains of headache, pruritus, urinary retention or any other neurological symptoms [Table 3].
Table 3: Intra-operative events

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   Discussion Top

This present prospective study evaluated the efficacy of pre-emptive analgesia of oral clonidine for laparoscopic gynecological procedures under subarachnoid block. Laparoscopic procedures performed under regional analgesia are advantageous due to reduction of surgical stress response, avoidance of airway instrumentation and lower incidence of deep vein thrombosis. The respiratory control mechanism remains intact to allow patients to adjust their minute ventilation and patients maintain an unchanged end tidal carbon dioxide. The low intra-abdominal pressure with slow insufflation flow rate contributes only few hemodynamic changes. The shoulder pain, secondary to diaphragmatic irritation from carbon dioxide pneumoperitoneum and anxiety are incompletely alleviated using subarachnoid block alone for laparoscopic procedures. [6],[7],[8],[9]

The choice of premedication, anesthetic technique, analgesia and cardiopulmonary status of patient has implication for the intra-operative course and post-operative outcome during laparoscopic gynecological procedures. Preemptive analgesia given before noxious stimulation is more effective to control the peri-operative pain by protecting the central nervous system from deleterious effects of noxious stimuli by establishing the central sensitization. [2]

The premedication of oral clonidine decreases the intra-operative stress response by reducing the nociceptive transmission and decreases the sympathetic outflow by activating the α2-adrenergic receptors in the brain and spinal cord. The analgesia produced by clonidine was due to their action at spinal, supra-spinal and or direct analgesic action. [10],[11] In our study, pre-emptive analgesia with oral clonidine has enhanced the onset of spinal anesthesia, prolonged the duration of analgesia and provided clinically effective sedation without any respiratory depression. Our results are inconsistent with the study of Pusapati et al. [12]

During the study, the hemodynamic changes were also minimal due to preloading with 15 ml/kg of Ringer lactate and low intra-abdominal pressure. The study also did not show any notable events apart from hypotension, which was easily treated by vasopressor drugs. The regional sympathetic block has compensated for increased sympathetic tone resulting from pneumoperitoneum. Clonidine is known to cause bradycardia and regional anesthesia also facilitates the unopposed vagal reflex, but none of our patients suffered bradycardia. The increase in hemodynamic values in patients of the control group may be due to inadequate sedation and analgesia.

Hayashi and Maze [13] and Sung et al. [14] in their study have reported that clonidine increases peri-operative circulatory stability in patients undergoing laparoscopic cholecystectomy and potentiate parasympathetic nervous system. Laisalmi et al. also concluded that premedication with clonidine blunts the stress response to surgical stimuli and reduces the requirement of narcotic analgesic doses. [15] The hemodynamic results of our study are in agreement with their results.

Bejarano González-Serna et al. concluded that spinal anesthesia is feasible and well-tolerated with midazolam sedation for laparoscopic ventral hernia. [16] Lau et al. quoted that laparoscopic hernia can be performed successfully under spinal anesthesia. [17]

Regional anesthesia produces vasodilation, which facilitate core to peripheral redistribution of heat and cause shivering. Clonidine decreases the thermoregulatory threshold for vasoconstriction and shivering. Tewari et al. and Dhorigol et al. found that oral clonidine 150 μg is efficacious to control shivering during subarachnoid block. [18],[19] In our study, no patient of clonidine group suffered from shivering while shivering occurred in seven patients of the control group.

During the laparoscopic procedures, the incidence of nausea and vomiting may be as high as 42% due to rapid peritoneal distension. In the present study, intravenous ondansetron with metoclopramide was given as prevention of nausea and vomiting. The metoclopramide acts both centrally and peripherally by speeding gastric empting time and increases the tone of the lower esophageal sphincter. Post-operative nausea and vomiting were found in only five patients of our study which was managed with intravenous ondansetron.

Lack of complication and morbidity encourage us to share our preliminary experience of pre-emptive analgesia with clonidine for laparoscopic gynecological procedures under subarachnoid block.

   Conclusion Top

The pre-emptive analgesia with oral clonidine was efficacious for elective laparoscopic gynecological procedures performed under subarachnoid block by enhancing the onset of spinal anesthesia and prolonging the duration of analgesia. Clonidine provided clinically significant sedation without respiratory depression, anxiety and alleviating shoulder pain, thus opens up further indications in obese and hypertensive patients for laparoscopic procedures under subarachnoid block.

   References Top

1.Chilvers CR, Goodwin A, Vaghadia H, Mitchell GW. Selective spinal anesthesia for outpatient laparoscopy. V: Pharmacoeconomic comparison vs general anesthesia. Can J Anaesth 2001;48:279-83.  Back to cited text no. 1
2.Woolf CJ, Chong MS. Preemptive analgesia - Treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993;77:362-79.  Back to cited text no. 2
3.Kanazi GE, Aouad MT, Jabbour-Khoury SI, Al Jazzar MD, Alameddine MM, Al-Yaman R, et al. Effect of low-dose dexmedetomidine or clonidine on the characteristics of bupivacaine spinal block. Acta Anaesthesiol Scand 2006;50:222-7.  Back to cited text no. 3
4.Rhee K, Kang K, Kim J, Jeon Y. Intravenous clonidine prolongs bupivacaine spinal anesthesia. Acta Anaesthesiol Scand 2003;47:1001-5.  Back to cited text no. 4
5.Joris JL, Chiche JD, Lamy M. Clonidine reduced hemodynamic changes induced by pneumoperitoneum during laparoscopic cholecystectomy. Br J Anaesth 1995;74:A124.  Back to cited text no. 5
6.Tzovaras G, Fafoulakis F, Pratsas K, Georgopoulou S, Stamatiou G, Hatzitheofilou C. Laparoscopic cholecystectomy under spinal anesthesia: A pilot study. Surg Endosc 2006;20:580-2.  Back to cited text no. 6
7.Gramatica L Jr, Brasesco OE, Mercado Luna A, Martinessi V, Panebianco G, Labaque F, et al. Laparoscopic cholecystectomy performed under regional anesthesia in patients with chronic obstructive pulmonary disease. Surg Endosc 2002;16:472-5.  Back to cited text no. 7
8.Savas JF, Litwack R, Davis K, Miller TA. Regional anesthesia as an alternative to general anesthesia for abdominal surgery in patients with severe pulmonary impairment. Am J Surg 2004;188:603-5.  Back to cited text no. 8
9.Sarli L, Costi R, Sansebastiano G, Trivelli M, Roncoroni L. Prospective randomized trial of low-pressure pneumoperitoneum for reduction of shoulder-tip pain following laparoscopy. Br J Surg 2000;87:1161-5.  Back to cited text no. 9
10.Elia N, Culebras X, Mazza C, Schiffer E, Tramèr MR. Clonidine as an adjuvant to intrathecal local anesthetics for surgery: Systematic review of randomized trials. Reg Anesth Pain Med 2008;33:159-67.  Back to cited text no. 10
11.Kaabachi O, Zarghouni A, Ouezini R, Abdelaziz AB, Chattaoui O, Kokki H. Clonidine 1 microg/kg is a safe and effective adjuvant to plain bupivacaine in spinal anesthesia in adolescents. Anesth Analg 2007;105:516-9.  Back to cited text no. 11
12.Pusapati RN, Sivashanmugam T, Ravishankar M. Respiratory changes during spinal anaesthesia for gynaecological laparoscopic surgery. J Anaesthesiol Clin Pharmacol 2010;26:475-9.  Back to cited text no. 12
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13.Hayashi Y, Maze M. Alpha 2 adrenoceptor agonists and anaesthesia. Br J Anaesth 1993;71:108-18.  Back to cited text no. 13
14.Sung CS, Lin SH, Chan KH, Chang WK, Chow LH, Lee TY. Effect of oral clonidine premedication on perioperative hemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy. Acta Anaesthesiol Sin 2000;38:23-9.  Back to cited text no. 14
15.Laisalmi M, Koivusalo AM, Valta P, Tikkanen I, Lindgren L. Clonidine provides opioid-sparing effect, stable hemodynamics, and renal integrity during laparoscopic cholecystectomy. Surg Endosc 2001;15:1331-5.  Back to cited text no. 15
16.Bejarano González-Serna D, Utrera A, Gallego JI, Rodríguez R, De la Portilla F, Espinosa JE, et al. Laparoscopic treatment of ventral hernia under spinal anesthesia. Cir Esp 2006;80:168-70.  Back to cited text no. 16
17.Lau H, Wong C, Chu K, Patil NG. Endoscopic totally extraperitoneal inguinal hernioplasty under spinal anesthesia. J Laparoendosc Adv Surg Tech A 2005;15:121-4.  Back to cited text no. 17
18.Tewari A, Katyal S, Singh A, Garg S, Kaul TK, Narula N. Prophylaxis with oral clonidine prevents perioperative shivering in patients undergoing transurethral resection of prostrate under subarachnoid block. Indian J Urol 2006;22:208-12.  Back to cited text no. 18
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19.Dhorigol MG, Dhulkhed VK, Biyani A, Desai N. Randomized, controlled double blind study to evaluate oral clonidine to prevent post-subarachnoid block shivering in patients undergoing elective urological surgery. J Anaesthesiol Clin Pharmacol 2010;26:15-8.  Back to cited text no. 19
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  [Figure 1]

  [Table 1], [Table 2], [Table 3]

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