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Year : 2006  |  Volume : 22  |  Issue : 3  |  Page : 208-212

Prophylaxis with oral clonidine prevents perioperative shivering in patients undergoing transurethral resection of prostate under subarachnoid blockade

Department of Anaesthesiology and Resuscitation, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Correspondence Address:
Anurag Tewari
Dayanand Medical College and Hospital, Ludhiana, Punjab - 141 001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0970-1591.27626

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BACKGROUND: We investigated the efficacy of oral clonidine 150 mg to prevent perioperative shivering in patients undergoing transurethral resection of prostate under subarachnoid block. Geriatric patients who undergo transurethral resection of prostate are prone to perioperative shivering during spinal anesthesia. Use of prophylactic oral clonidine, which is known to reduce shivering, could lead to decrease in the morbidity and mortality of such patients. MATERIALS AND METHODS: In this prospective double blinded placebo-controlled study, 80 patients scheduled for transurethral resection of prostate surgery under subarachnoid block were randomized into two groups. Group I (n=40) received oral clonidine 150 mg, while Group II (n=40) were given placebo tablet. After achieving subarachnoid block, the incidence, severity and duration of shivering was recorded and compared in both the groups. The body temperature (axillary, forehead and tympanic membrane), hemodynamic parameters and arterial saturation were recorded at regular intervals. RESULTS: Incidence of shivering was significantly less in patients who were given oral clonidine when compared with that of the placebo group (5 vs. 40% respectively; P value of <0.01). Clonidine did not lead to any collateral clinically significant side effects. CONCLUSION: We conclude that as a prophylaxis oral clonidine 150 mg is effective in reducing the incidence, severity and duration of perioperative shivering in patients undergoing transurethral resection of prostate surgery under spinal anesthesia.

Keywords: Clonidine, perioperative shivering, spinal anesthesia, transurethral resection of prostate surgery

How to cite this article:
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 blockade. Indian J Urol 2006;22:208-12

How to cite this URL:
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 blockade. Indian J Urol [serial online] 2006 [cited 2022 Dec 10];22:208-12. Available from:

   Introduction Top

Perioperative shivering during spinal anesthesia is a common complication in patients undergoing transurethral resection of prostate (TURP) and is secondary to peripheral vasodilatation from sympathetic blockade and/or cold irrigating fluids.[1] Regional anesthesia has been known to be associated with greater heat loss than general anesthesia.[2] Elderly patients are especially at risk of hypothermia under anesthesia, as low core temperatures may not initiate autonomic protective responses.[3] Perioperative shivering may be physically detrimental and embarrassing. It may be associated with a number of deleterious sequelae, including sympathetic stimulation induced increased oxygen consumption[4] (more than 200%) and carbon dioxide production[5] that may induce myocardial infarction. Unfortunately the emphasis is to treat it rather than prevent it.

Pharmacologically oral clonidine virtually undergoes complete absorption[6] and the peak concentration occurs after 1.5 h after administration.[7] Clonidine, a centrally acting a 2-selective agonist, has been used intravenously as an adjunct to general anesthesia to decrease shivering and oxygen consumption. The anatomic target of its anti-shivering effect can be found at three levels. It decreases the thermoregulatory threshold for vasoconstriction and shivering as hypothalamus contains a high density of a 2 adrenoreceptors. It also reduces spontaneous firing in locus coeruleus - a pro-shivering center in pons.[8] a 2 adrenoreceptors in the spinal cord also get activated to release dynorphine (an opioid agonist), norepinephrine and acetylcholine. The depressor effects of these neurotransmitters at the dorsal horn modulate cutaneous thermal inputs in addition to noxious and mechanoreceptive transmission.[9] It is highly lipid-soluble and easily crosses the blood-brain barrier.[10] These merits make it to interact at the a 2 adrenoreceptors at spinal and supraspinal sites within the central nervous system.[11] Oral clonidine 150 mg given 1.5 h before spinal anesthesia has been shown to improve both the quality and duration of spinal anesthesia without any side effects.[12] In India the intravenous formulation of clonidine is not yet available, while the oral formulation is cheap and easily procurable. Our study tries to evaluate the prophylactic efficacy of the oral formulation for prevention of perioperative shivering in patients undergoing transurethral resection of prostate as most of the previous studies have concentrated on the intravenous form.

   Materials and methods Top

After approval from institutional ethical committee and written informed consent, 80 patients (American Society of Anesthesiologists Grade I, II, III) scheduled for elective transurethral resection of prostate surgery under subarachnoid blockade were enrolled into the study. Patients who were obese (Body Mass Index >30%), febrile or had any history suggestive of allergy to clonidine, heart disease (bradycardia, hypotension, severe atrioventricular block), cerebrovascular disease, thyroid dysfunction, severe diabetic / autonomic neuropathy, infection of the urinary tract or the external auditory meatus were excluded. Those patients who were taking vasodilators likely to cause alteration in thermoregulation were not included in the study.

Anesthesiology department technologists, who were not involved in the study, prepared the trial preparations and recorded the group randomization separately. The anesthesiologist conducting the case and recording the data was unaware of the preparation administered. Patients were randomly assigned to two groups (by random number table), each receiving a sealed envelop of oral formulation 90 min prior to the surgery. Group I (n=40) received oral clonidine 150 mg, while the Group II (n=40) received starch tablets.

Subarachnoid blockade up to T 9-10 dermatome level was achieved with heavy Bupivacaine (0.5%), 10-15 mg (average 12 mg). All operations were performed in the same operation theater, which was maintained at a constant humidity and an ambient temperature of around 22 1C. No means of active rewarming were used. The operating room was not equipped to provide laminar flow. Prewarmed (up to the body temperature of 37C) intravenous and irrigating fluids were used perioperatively.

Heart rate, noninvasive blood pressure, respiratory rate, SpO 2 , body temperature (axillary and forehead, using the Excel 210 temperature probes) and tympanic membrane temperature (using the Braun Thermoscan) were recorded every 5 min from the baseline (when SAB was given) for 1 h and thereafter every 15 min for the rest of the observation period. In all the cases, shivering was recorded by the same attending anesthesiologist at a period of 0, 1, 5, 10, 15, 30, 45, 60 and 90 min from the baseline as per grades given by Wrench[13] [Table - 1].

Perioperatively if shivering occurred, it was treated in the same manner in both groups - with reassurance, warming blanket or meperidine. Forced-air warming blankets were available when necessary. Associated conditions like sedation, bradycardia (heart rate <50/min) and hypotension (systolic blood pressure <30% of baseline) were recorded. Bradycardia and hypotension were appropriately treated with atropine and mephentermine respectively in titrated doses when required. The sedative side effects of clonidine were assessed with a four-point scale (sedation score) as per Filos[14] [Table - 2].

Statistical analysis

The SPSS version 7.5 was used for statistical analysis. All the data was tabulated and expressed as mean standard deviation. Parametric data was analyzed using student 't' test and analysis of variance (ANOVA) test, while the nonparametric values were analyzed using the test of proportions, i.e., 'Z' test. We used the Fisher exact test to compare the incidences between the two groups. A P <0.05 was considered statistically significant. No power analysis could be done before choosing the number of patients for the study, as the exact incidence of perioperative shivering during TURP surgery under spinal anesthesia was not available despite the best of our efforts. However, the power of our study is the large number of patients in comparison to other studies.


The demographic data, duration of the surgery and time required to achieve a Bromage score of 4 were similar amongst both the groups [Table - 3]. Incidence of shivering [Figure - 1] was significantly less in Group I (5%) when compared with that of the Group II (40%). In the study group, 38 patients (95%) did not experience shivering. Of the 2 patients who shivered, one had grade 1 shivering that progressed to grade 2. The second patient experienced shivering of grade 1 only. In the placebo group, 24 patients (60%) did not shiver, while 16 patients (40%) experienced various grades of shivering, ranging from grade 1 to grade 4. Many patients progressed from low to high grades of shivering. On comparison, a P value <0.01 was observed, thus implying a statistically significant variance regarding the incidence amongst them. We observed that 15 (37.5%), 11 (27.5), 10 (25) and 5 (12.5%) patients in the control group experienced grades 1, 2, 3 and 4 of shivering respectively at various time intervals during the study period [Table - 4]. The variation was significant throughout the period of study, especially at 30, 45 and 60 minutes' intervals, where the P value <0.01 was observed; while at 5, 10, 15 and 90 minutes' intervals, the P value was <0.05. It was observed that shivering started earlier (in 5 min) and persisted for a longer duration in control group (range 5-90 min); while in the patients who were administered prophylactic oral clonidine, its onset was delayed and was of a shorter duration (range 15-60 min). All the patients who experienced grade 3-4 of shivering had tachycardia, increased blood pressure recording and decrease in arterial oxygen saturation. Three patients in the control group who experienced grade 4 of shivering had premature ventricular contractions, which were successfully treated with intravenous xylocard 2% (1.5 mg/kg).

The tympanic membrane temperature [Figure - 2] showed statistically significant variation, especially in the later part of the study ( P < 0.01), while axillary and forehead temperatures were similar throughout the study [Figure - 3][Figure - 4] respectively. There was no statistical variance when the blood pressure, respiratory rate and SpO 2 were compared.

When the heart rates were compared, the patients in the clonidine group had lower heart rate compared to the control group throughout the study, but it did not cause any clinically significant hemodynamic aberrations [Figure - 5]. Two patients (5%) in the clonidine group and three patients (7.5%) in the control group had bradycardia. This was treated by atropine 0.3-1.2 mg. Hypotension was observed in five (12.5%) and seven patients (17.5%) in clonidine and control group respectively [Table - 5]. This was successfully ameliorated with mephentermine 6-12 mg.

Sedation of grade 2 was observed in five (12.5%) and three (7.5%) patients in clonidine and control group respectively. No patient of either group experienced grade 3 or 4 sedation.

   Discussion Top

Previous studies under spinal anesthesia concerned with timing and dosage response of oral clonidine governed our using 150 mg oral clonidine 90 min prior to subarachnoid blockade.[15] In our study oral clonidine was saliently effective in providing prophylaxis against shivering in TURP surgery under subarachnoid blockade. The incidence of shivering in patients who were given oral clonidine was only 5% as compared to 40% in the control group ( P <0.01). This is comparable to Mao,[15] who also found an incidence of 4% when patients were given clonidine as compared to 44% in the control group.

The 5% patients who shivered in the clonidine group experienced only Grade I and/or II of shivering as compared to the control group in which the patients experienced shivering ranging from Grade I to IV. It was observed that shivering had early onset and persisted longer in control group, while in the clonidine group shivering had a delayed onset and persisted for a shorter duration. This is in concordance with various studies, which showed that clonidine reduces the incidence, severity and duration of perioperative shivering.[13]

We found that the lowest mean temperature was at 45 and 50 min in control and clonidine groups respectively. This is in variance to the study by Mao,[15] who did not observe any fall in the tympanic membrane temperature. It may be because they recorded tympanic membrane temperature at the 30-minute interval after subarachnoid blockade.

There was no significant variation in the blood pressure of the patients of the two groups ( P <0.01) though five patients in clonidine and seven in placebo group required mephentermine. This was not clinically significant and is comparable to other studies.[16] There was a significant fall in heart rate (clinically insignificant) of the patients who were given clonidine, within and amongst ( P <0.01) the two groups.

The usual elderly-age and associated medical problems of the patients undergoing TURP pose a significant cardiac risk. Thus the incidence of cardiovascular complications is higher as compared to other noninvasive urological procedures.[17] In regional anesthesia, major conduction blockade significantly impairs the regulation of body temperature by inhibition of vasomotor and shivering responses and by redistribution of heat from core of the body to the peripheral tissue.[18] Maintaining strict normothermia can prevent shivering during regional anesthesia.[19]

In patients with benign prostatic hypertrophy, transurethral prostatectomy is considered the best treatment for relieving obstruction of the urinary bladder.[20] Most of the morbidity and mortality is associated with the cardiovascular system, with myocardial infarction, cardiac arrest, heart failure or cardiac dysrhythmias occurring in up to 2.5% of patients.[21],[22] The incidence of cardiovascular complications is higher than expected for a noninvasive procedure. This could be due to the medical state of the patients or TURP-related adverse effects, including hypervolemia, hypovolemia, hypothermia, hypotension, glycine absorption, hyperammonia, hyponatremia and sepsis.[23] Studies have reported reduction in core temperature during transurethral prostatectomy.[24],[25],[26] The cardiovascular system could be adversely affected by perioperative reduction in core temperature and metabolic demands. Hypothermia causes bradycardia, reduced cardiac output and peripheral vasoconstriction. There are additional adverse affects on every other body system.[27] The cardiovascular system is stressed as a result of increased after-load effects on myocardial excitability and conduction and the metabolic demands of rewarming.[13] The metabolic cost of shivering is an increase in oxygen consumption from 300 to 800%.[4] Rapid reduction in core temperature starts with bladder irrigation during transurethral prostatectomy as unheated irrigating fluid is used and could be a significant etiological factor in the production of the hemodynamic responses observed.[18] We therefore undertook the study in TURP surgery as these patients are predisposed to shivering and any therapeutic effect of our study might prove beneficial for such patients.

Oral clonidine is easily available and economical (one tablet costs less than a rupee) and its salient attributes are its high safety profile, particularly in geriatric patients. It has a potential to prevent perioperative morbidity associated with shivering and leads to shorter hospital stay. To conclude, we suggest that oral clonidine should be used prophylactically to prevent shivering in patients undergoing TURP surgery under subarachnoid blockade in this group of patients, since it is easily available and cheap.[28]

   References Top

1.Chow TC, Cho PH. The influence of small dose intrathecal fentanyl on shivering during transurethral resection of prostate under spinal anaesthesia. Acta Anaesthesiol Sin 1994;32:165-70.   Back to cited text no. 1  [PUBMED]  
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4.Harvath SM, Spurr GB, Hutt BK, Hamilton LH. Metabolic cost of shivering. J Appl Physiol 1956;8:595-602.   Back to cited text no. 4    
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8.Powell RM, Buggy DJ. Ondansetron given before induction of anaesthesia reduces shivering after general anaesthesia. Anesth Analg 2000;90:1423-7.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Alojado ME, Ohta Y, Kemmotsu O. The effect of clonidine on the activity of neurons in the rats dorsal raphe nucleus in vitro . Anesth Analg 1994;79:257-60.  Back to cited text no. 9  [PUBMED]  
10.Timmermans PB, Brands A, van Zwietan PA. Lipophilicity and brain disposition of clonidine and structurally related imidazolidines. Naunyn-Schmiedeberg Arch Pharmacol 1977;300:217-26.  Back to cited text no. 10    
11.Klimcsha W, Tong C, Eisenach JC. Intrathecal alpha-2 adrenergic agonists stimulate acetylcholine and norepinephrine release from the spinal cord dorsal horn in sheep. An in vivo microdialysis study. Anesthesiology 1997;87:110-6.  Back to cited text no. 11    
12.Liu S, Chiu AA, Neal JM, Carpenter RL, Bainton BG, Gerancher JC. Oral clonidine prolongs lidocaine spinal anaesthesia in human volunteers. Anesthesiology 1995;82:1353-9.  Back to cited text no. 12    
13.Wrench IJ, Singh P, Dennis AR, Mahajan RP, Crossley AW. The minimum effective doses of pethidine and doxapram in the treatment of post-anaesthetic shivering. Anaesthesia 1977;52:32-6.  Back to cited text no. 13    
14.Filos KS, Goudas LC, Patroni O, Polyzou V. Hemodynamic and analgesic profile after intrathecal clonidine in humans. A dose-response study. Anesthesiology 1994;81:591-601.  Back to cited text no. 14    
15.Mao CC, Tsou MY, Chia YY, Chow LH, Chan KH. Lee TY. Pre-anaesthetic oral clonidine is effective to prevent post spinal shivering. Acta Anaesthesiol Sin 1998;36:137-42.   Back to cited text no. 15    
16.Vanderstappen I, Vandermeersh E, Vanacker B, Mattheussan M, Herijgers P, Van Aken H. The effect of prophylactic clonidine on postoperative shivering. A large prospective double blind study. Anaesthesia 1996;51:351-5.   Back to cited text no. 16    
17.Mercadante S, De Michele P, Letterio G, Pignataro A, Sapio M, Villari P. Effect of clonidine on post partum shivering after epidural analgesia: A randomized, controlled, double blind study. J Pain Symptom Manage 1994;9:294-7.  Back to cited text no. 17    
18.Evans JW, Singer M, Chapple CR, Macartney N, Walke JM, Milroy EJ. Haemodynamic evidence for cardiac stress during transurethral prostatectomy. Br Med J 1992;304:666-71.  Back to cited text no. 18    
19.Holdcraft A, Hall GM. Heat loss during anaesthesia. Br J Anaesth 1978;50:157-64.  Back to cited text no. 19    
20.Chisholm GD. Benign prostatic hyperplasia. The best treatment. Br Med J 1989;299:215-6.  Back to cited text no. 20  [PUBMED]  
21.Holtgrewe HL, Valk WL. Factors influencing the mortality and morbidity of transurethral prostatectomy: A study of 2015 cases. J Urol 1962;87:450-9.  Back to cited text no. 21  [PUBMED]  
22.Melchior J, Valk WL, Foret JD, Mebust WK. Transurethral prostatectomy, computerized analysis of 2223 consecutive cases. J Urol 1974:112:634-42.  Back to cited text no. 22    
23.Neal DE. Prostatectomy-an open or shut case. Br J Urol 1990;66:449-54.  Back to cited text no. 23  [PUBMED]  
24.Rabke HB, Jenicek JA, Khouri E Jr. Hypothermia associated with transurethral resection of prostate. J Urol 1962;87:447-9.  Back to cited text no. 24  [PUBMED]  
25.Rawstron RE, Walton JK. Body temperature changes during transurethral prostatectomy. Anaesth Intens Care 1981;9:43-6.  Back to cited text no. 25  [PUBMED]  
26.Carpenter AA. Hypothermia during transurethral resection of prostate. Urology 1984;23:122-4.  Back to cited text no. 26  [PUBMED]  
27.Carli F. Metabolic disturbances of hypothermia. In Balltere's Clinical Anaesthesiology 1989;3:405-21.  Back to cited text no. 27    
28.Wrench IJ, Singh P, Dennis AR, Mahajan RP, Crossley AW. The minimum effective dose of pethidine and doxapram in the treatment of post-anaesthetic shivering. Anaesthesia 1997;52:32-6.  Back to cited text no. 28    


  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5]

  [Table - 1], [Table - 2], [Table - 3], [Table - 4], [Table - 5]

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