|Year : 2016 | Volume
| Issue : 3 | Page : 143-147
Oral clonidine for shivering prophylaxis in patients undergoing elective urological surgeries under subarachnoid anesthesia
Aparna Bagle, Widya Thatte, Sonal Khatavkar, Sandeep Choudhary, Bharat Vagasia
Department of Anaesthesia, Dr. D Y Patil Medical College, Pimpri, Pune, Maharashtra, India
|Date of Web Publication||5-Aug-2016|
Dr. Aparna Bagle
Department of Anaesthesia, Dr. D Y Patil Medical College, Pimpri, Pune - 411 018, Maharashtra
Source of Support: None, Conflict of Interest: None
Background and Aim: Perioperative shivering during subarachnoid anesthesia is a common complication in patients undergoing urological procedures. It is secondary to peripheral vasodilatation from sympathetic blockade and/or cold irrigating fluids. Previous studies mainly emphasized on treating shivering rather than preventing it. Therefore, our aim was to evaluate the prophylactic efficacy of the oral formulation of clonidine for prevention of perioperative shivering in patients undergoing urological procedures under subarachnoid anesthesia and also to evaluate any side effects associated with it. Materials and Methods: A total of 60 patients scheduled for elective urological surgeries under subarachnoid blockade were enrolled into this prospective, randomized, double-blind controlled study. Patients were randomly assigned to two groups. Group C (n = 30) received oral clonidine 0.1 mg tablets, whereas Group P (n = 30) received folic acid 5 mg (placebo) tablets 90 min before surgery. Subarachnoid blockade was administered with heavy bupivacaine (0.5%), 3 ml (15 mg). All procedures were performed in the similar operation theater conditions. Hemodynamic parameters, axillary temperature, and shivering were recorded. Any side effects were recorded and treated appropriately. P <0.05 was considered statistically significant. Results: Incidence of shivering was significantly less in Group C (10%) when compared with that of the Group P (40%) (P < 0.01). Patients in Group C had Grade 1 or 2 shivering while in the Group P patients experienced various grades of shivering ranging from Grades 1 to 4. Conclusion: Incidence and severity of perioperative shivering was significantly less (P < 0.05) in clonidine group without significant side effects.
Keywords: Clonidine, shivering, urological surgeries
|How to cite this article:|
Bagle A, Thatte W, Khatavkar S, Choudhary S, Vagasia B. Oral clonidine for shivering prophylaxis in patients undergoing elective urological surgeries under subarachnoid anesthesia. Int J Health Allied Sci 2016;5:143-7
|How to cite this URL:|
Bagle A, Thatte W, Khatavkar S, Choudhary S, Vagasia B. Oral clonidine for shivering prophylaxis in patients undergoing elective urological surgeries under subarachnoid anesthesia. Int J Health Allied Sci [serial online] 2016 [cited 2022 Dec 8];5:143-7. Available from: https://www.ijhas.in/text.asp?2016/5/3/143/187798
| Introduction|| |
Subarachnoid (spinal) anesthesia is widely used as a safe anesthesia technique for both elective and emergency surgeries. Shivering is a frequent complication, distressing for the patients undergoing surgery under both regional and general anesthesia. Shivering is reported in 40-70% of patients undergoing surgery under regional anesthesia. ,, Perioperative shivering is a common complication in patients undergoing urological procedures under subarachnoid anesthesia. Shivering may be secondary to peripheral vasodilatation from sympathetic blockade and/or cold irrigating fluids.  Regional anesthesia has been known to be associated with greater heat loss than general anesthesia. Perioperative shivering may be associated with a number of deleterious sequelae. Sympathetic stimulation due to shivering elevates blood pressure, heart rate, plasma catecholamine concentrations, increased metabolic rate, increased oxygen consumption (100-600%) along with increased carbon dioxide production. These factors may contribute to threefold increase in morbid myocardial outcomes.  Most of the time, the emphasis is to treat perioperative shivering rather than prevent it.
Clonidine, the α2 -agonist has shown properties that are potentially beneficial for premedication for anxiolysis, preoperative sedation, to reduce sympathetic activity, to diminish incidence of shivering and oxygen consumption during recovery from anesthesia, to decrease anesthetic and analgesic requirement and to minimize postoperative pain, nausea, and vomiting. ,
Clonidine hydrochloride is available as tablets for oral administration in three dosage strengths 0.1 mg, 0.2 mg, and 0.3 mg. The 0.1 mg tablet is equivalent to 0.087 mg of the free base. Clonidine reduces the thermoregulatory threshold for vasoconstriction and shivering.  Oral clonidine given 90 min before subarachnoid anesthesia has been shown to improve both the quality and duration of spinal anesthesia without any side effect.  Oral formulation is cheap and easily available. We evaluated the prophylactic efficacy of the oral formulation of clonidine for prevention of perioperative shivering in patients undergoing urological procedures under subarachnoid anesthesia.
| Materials and Methods|| |
After approval from the Institutional Ethics Committee, this prospective, randomized, double-blind controlled study was carried out in the Department of Anesthesiology from February 2014 to September 2014.
After written informed consent, sixty patients aged between 18 and 70 years, American Society of Anesthesiologists physical status I and II scheduled for elective urological surgeries under subarachnoid anesthesia were enrolled into the study.
Patients who were obese (body mass index >30 kg/m2), febrile, having any history suggestive of allergy to clonidine, bradycardia, hypotension, severe atrioventricular block, heart disease, cerebrovascular disease, thyroid dysfunction, and severe diabetic/autonomic neuropathy were excluded from the study. Those patients taking vasodilators, likely to cause alteration in thermoregulation were also excluded from the study. Patients were randomly assigned to two groups; each group was receiving a sealed envelope of oral formulation 90 min before the surgery. Randomization was done using computer-generated random number table. Anesthesiologists involved in the study recorded the group randomization separately. The anesthesiologist, conducting the case and recording the data were unaware of the tablet administered.
Group C (n = 30) received oral clonidine 0.1 mg tablets.
Group P (n = 30) received folic acid 5 mg (placebo) tablets.
Both tablets were similar looking in size and shape.
All patients were thoroughly evaluated preoperatively. All the necessary and relevant laboratory investigations were carried out. Subarachnoid anesthesia was given with spinal needle 26 gauge in sitting position. Subarachnoid blockade was achieved up to T 8-9 dermatome level with heavy bupivacaine (0.5%) 3 ml (15 mg). All operations were performed in the similar operation theater conditions, which were maintained at a constant humidity and an ambient temperature of around 22°C ± 1°C. No means of active rewarming was used as preventive measure. The operating room was not equipped to provide laminar flow. Oxygen was administered to all the patients of both groups at a rate of 4 L/min with venturi mask (FiO 2 = 0.28) and patients were covered with drapes, but not actively warmed.  Intravenous (IV) fluids and anesthetic drugs were administered at room temperature. Heart rate, noninvasive blood pressure, respiratory rate, oxygen saturation (SpO 2 ), and body temperature (axillary) were recorded as baseline (before subarachnoid anesthesia) and every 15 min (after subarachnoid anesthesia was administered) until the patient was shifted to the recovery room. Patients were shifted to the ward from recovery room after wearing of motor blockade. In recovery room, heart rate, noninvasive blood pressure, respiratory rate, peripheral SpO 2 , and body temperature (axillary) were recorded every 15 min until patient was shifted to the ward. In all the cases, shivering was recorded by the same attending anesthesiologist at a period of 0, 15, 30, 45, 60, and 90 min according to grades given by Wrench. 
Grade 0: No shivering
Grade 1: One or more of the following: Piloerection, peripheral cyanosis without other cause, but without visible muscle activity
Grade 2: Visible muscle activity confined to one muscle group
Grade 3: Visible muscle activity in more than one muscle group
Grade 4: Gross muscle activity involving the whole body.
Perioperatively if shivering occurred; it was treated in the same manner in both groups with reassurance, warming blanket and injection tramadol (1 mg/kg) along with injection ondansetron 4 mg was given intravenously. Associated conditions such as sedation, bradycardia and hypotension were recorded and treated appropriately.
The sedative effect of clonidine was assessed using sedation score according to Filos. 
- Awake and alert
- Drowsy, but responsive to verbal stimuli
- Drowsy, but arousable to physical stimuli
All cases completed in stipulated time. Data were collected, compiled, and tabulated. Statistical analysis was performed using statistical software (SPSS Inc. 233 South Wacker Drive, 11 th Floor Chicago, IL) version 13. All results were expressed as mean ± standard deviation. Unpaired t-test and Chi-square test were applied for the interpretation of results. P < 0.05 was considered statistically significant.
| Results|| |
Age, weight, sex, and duration of surgery were comparable in both the groups and no statistically significant difference was observed among the groups [Table 1].
Changes in hemodynamic parameters (heart rate and mean blood pressure) were comparable in both groups and were not significant statistically as well as clinically [Graph 1].
Fall in axillary temperature after spinal anesthesia was observed in both the groups, but was not statistically and clinically significant [Graph 2].
Incidence of shivering [Graph 3] was significantly less in Group C (10%) when compared with that of the Group P (40%). In Group C, three patients who shivered, had Grade 1 or Grade 2 shivering [Table 2]. Twelve patients (40%) experienced various grades of shivering ranging from Grade 1 to Grade 4 in Group P. On comparison P < 0.01 was observed, this implying a statistically significant difference between them.
Sedation of Grade 2 was observed in fifteen and six patients in Group C and Group P, respectively and in five patients Grade 3 sedation observed in Group C. No patient of either group experienced Grade 4 sedation [Table 3].
When the heart rate was compared, the patients in the Group C had lower heart rate compared to the Group P throughout the study, but it did not cause any clinically significant hemodynamic aberrations. Three patients in Group C and one patient in Group P had bradycardia [Table 4]. This was treated by injection atropine 0.6 mg. Hypotension was observed in three and two patients in Group C and Group P, respectively. This was successfully treated with injection mephentermine 6-12 mg.
| Discussion|| |
Shivering is a common perioperative problem causing tachycardia, hypertension, and increased metabolic demands. It also causes interference with intraoperative monitoring of electrocardiogram, blood pressure, and SpO 2 . , Various risk factors associated with shivering include age, type, duration of anesthesia, level of sensory blockade and temperature of the operating room and infusion fluids. ,,, The metabolic cost of shivering is an increase in oxygen consumption by 200-800%. , Surgical patients should be kept normothermic, unless hypothermia is specially indicated. Hypothermia under spinal anesthesia is mainly due to three reasons, internal redistribution of heat from core to peripheral compartment, loss of thermoregulatory vasoconstriction below the level of spinal blockade leading to more heat loss from body surface and altered thermoregulation under spinal anesthesia characterized by a 0.5°C decrease in vasoconstriction and shivering thresholds.  There are many nonpharmacological and pharmacological methods used to prevent or decrease heat loss and shivering. Nonpharmacological methods include radiant heat warmers, warming the operation theater, warm blankets, warm IV fluids, and using anesthetic drugs at body temperature. Pharmacological methods to treat shivering include pethidine, tramadol, doxapram, ketanserin, nefopam, alfentanil, clonidine, etc. ,,,,,,,
In this study, we compared the efficacy of clonidine for prevention of shivering after spinal anesthesia in patients undergoing elective urological surgeries. Clonidine works at three levels, at hypothalamus, locus coeruleus, and spinal cord. At the hypothalamic level, clonidine decreases thermoregulatory threshold for vasoconstriction and shivering because hypothalamus has high density of alpha-2 adrenoreceptors.  Clonidine reduces spontaneous firing in locus coeruleus - a pro-shivering center in pons. Alpha-2 adrenoreceptors in the spinal cord also get activated to release norepinephrine, dynorphine (an opioid agonist), and acetylcholine. The depressor effects of these neurotransmitters modulate cutaneous thermal inputs at the dorsal horn in addition to noxious and mechanoreceptive transmission. Clonidine is highly lipid-soluble and easily crosses the blood-brain barrier. Due to these merits, interaction at the alpha-2 adrenoreceptors at spinal and supraspinal sites occurs within the central nervous system. 
In this study, the factors that influence the occurrence of shivering, as temperature of IV fluids and drugs, were not tightly controlled, but this should not affect the validity of our study because it was focused on prophylactic effect of clonidine on incidence and severity of shivering and both groups were subjected to similar degrees of influence of these factors.
Core temperature is most accurately measured in the pulmonary artery, distal part of esophagus, tympanic membrane, or nasopharynx.  Temperature monitoring at these sites are not comfortable for patients under spinal anesthesia, also core temperature can be estimated with reasonable accuracy using oral, axillary, rectal and bladder temperatures except during extreme thermal perturbations; therefore, we chose axillary temperature monitoring.
There was fall in heart rate and blood pressure in clonidine group as compared to placebo group, but the fall was not significant statistically and clinically. The lowest mean temperature was at 75 and 90 min for placebo and clonidine, respectively and decrease in temperature was not significant statistically and clinically. These observations were similar to the previous studies by various authors. ,,,,
The incidence of shivering in patients who were given oral clonidine was only 10% as compared to 40% in the placebo group (P < 0.01) which is similar to the study by Dhorigol et al., who found shivering incidence 12% in clonidine group while 55% in placebo group.  Three patients who shivered in the clonidine group had Grade 1 or 2 of shivering as compared to the placebo group in which the patients had shivering ranging from Grades 1 to 4. This is similar to various studies, which showed that clonidine decreases the incidence and severity of perioperative shivering. ,,,, A nonsignificant temperature difference was observed between clonidine and placebo group which indicated that decrease in the incidence of shivering in clonidine group was not related to modulation in body temperature, but was probably due to resetting of thermoreceptors at a lower threshold by the study drug.
The sedation score was more in clonidine group patients as compared to placebo group patients, but no patient had sedation score more than three and they were easily arousable. This was similar to the findings of Tewari et al. and Wason et al. , Oral clonidine is easily available, economical and having high safety profile. Anesthetic-induced hypothermia is known to reduce platelet function and impair enzymes of the coagulation cascade.  Thus perioperative hypothermia and shivering leads to increase blood loss during operation and delayed wound healing. Sympathetic stimulation due to shivering leads to increase in morbid myocardial outcomes. All these leads to prolongation of hospital stay. Clonidine has a potential to prevent shivering and peri-operative morbidity associated with shivering leading to shorter hospital stay.
| Conclusion|| |
Oral clonidine 0.1 mg given preoperatively is an effective measure to decrease incidence and severity of perioperative shivering in patients undergoing urological procedures under subarachnoid anesthesia.
Limitation of the study
Preoperative sedation and effect of oral clonidine on characteristics of subarachnoid anesthesia was not studied in detail in this study. Analgesic, sedative, antisecretory, and antiemetic effects of clonidine need further studies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Crowley LJ, Buggy DJ. Shivering and neuraxial anesthesia. Reg Anesth Pain Med 2008;33:241-52.
Attal P, Chhaya A, Singh T, Upadhyaya M. Comparison of clonidine and tramadol for control of shivering under spinal anaesthesia. Int J Biomed Adv Res 2015;6:26-9.
de Figueiredo Locks G. Incidence of shivering after cesarean section under spinal anesthesia with or without intrathecal sufentanil: A randomized study. Rev Bras Anestesiol 2012;62:676-84.
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 prostate under subarachnoid block. Indian J Urol 2006;22:208-12.
Sessler DI. Temperature regulation and monitoring. In: Miller RD, editor. Miller′s Anaesthesia. 7 th
ed. Philadelphia: Churchill Livingstone; 2010. p. 1533-56.
Majumdar S, Das A, Das H, Bandyopadhyay S, Hajra BK, Mukherjee D. Comparative evaluation of oral gabapentin versus clonidine as premedication on preoperative sedation and laryngoscopic stress response attenuation for the patients undergoing general anesthesia. Perspect Clin Res 2015;6:211-6.
Carabine UA, Wright PM, Moore J. Preanaesthetic medication with clonidine: A dose-response study. Br J Anaesth 1991;67:79-83.
Gupta K, Singh I, Singh VP, Prashant K, Gupta I, Tiwari V. Preemptive analgesia of oral clonidine during subarachnoid block for laparoscopic gynecological procedures: A prospective study. Anesth Essays Res 2014;8:187-91.
Wheeler DW. Equipment for the inhalation of oxygen and other gases. In: Davey AJ, editor. Ward′s Anaesthetic Equipment. 6 th
ed. Philadelphia: Elsevier Saunders; 2012. p 215-21.
Shukla U, Malhotra K, Prabhakar T. A comparative study of the effect of clonidine and tramadol on post-spinal anaesthesia shivering. Indian J Anaesth 2011;55:242-6.
Bansal P, Jain G. Control of shivering with clonidine, butorphanol, and tramadol under spinal anesthesia: A comparative study. Local Reg Anesth 2011;4:29-34.
Singh SN, Sah BP, Ghimire A, Prasad JN, Baral DD. Comparisons of tramadol with pethidine for prevention of post anaesthetic shivering in elective abdominal surgery. Health Renaiss 2012;10:220-23.
Goyal P, Kundra S, Sharma S, Grewal A, Kaul TK, Singh MR. Efficacy of intravenous fluid warming for maintenance of core temperature during lower segment cesarean section under spinal anesthesia. J Obstet Anesth Crit Care 2011;1:73-7.
Najafianaraki A, Mirzaei K, Akbari Z, Macaire P. The effects of warm and cold intrathecal bupivacaine on shivering during delivery under spinal anesthesia. Saudi J Anaesth 2012;6:336-40.
Reddy VS, Chiruvella S. Clonidine versus tramadol for post spinal shivering during cesarean section-a randomized double blind clinical study. J Obstet Anesth Crit Care 2011;1:26-9.
Zavaherforoush F, Pipelzadelimto, Bagherybarma F. Comparison of clonidine, pethedine and fentanyl for post spinal anaesthesia shivering in elective cesarean sections. Armghan Danesh Fall 2006;11:60-7.
Kranke P, Eberhart LH, Roewer N, Tramèr MR. Single-dose parenteral pharmacological interventions for the prevention of postoperative shivering: A quantitative systematic review of randomized controlled trials. Anesth Analg 2004;99:718-27.
Abdelrahman RS. Prevention of shivering during regional anaesthesia: Comparison of Midazolam, Midazolam plus ketamine, Tramadol, and Tramadol plus Ketamine. Life Sci J 2012;9:132-9.
Shakya S, Chaturvedi A, Sah BP. Prophylactic low dose ketamine and ondansetron for prevention of shivering during spinal anaesthesia. J Anaesthesiol Clin Pharmacol 2010;26:465-9.
Usta B, Gozdemir M, Demircioglu RI, Muslu B, Sert H, Yaldiz A. Dexmedetomidine for the prevention of shivering during spinal anesthesia. Clinics (Sao Paulo) 2011;66:1187-91.
Dhorigol MG, Dulkhed MK, Biyani A, Desai N. Randomised, 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.
Jabbar M, Omni D, Mirkheshti A. Effects of clonidine premedication upon post operative shivering and recovery time in patients with and without opium addiction after elective leg fracture surgeries. Anaesth Pain Med 2013;3:107-10.
Wason R, Jain N, Gupta P, Gogia AR. Randomized double-blind comparison of prophylactic ketamine, clonidine and tramadol for the control of shivering under neuraxial anaesthesia. Indian J Anaesth 2012;56:370-5.
Rajagopalan S, Mascha E, Na J, Sessler DI. The effects of mild perioperative hypothermia on blood loss and transfusion requirement. Anesthesiology 2008;108:71-7.
[Table 1], [Table 2], [Table 3], [Table 4]