|Year : 2015 | Volume
| Issue : 3 | Page : 407-412
Role of oral clonidine in preventing postsubarachnoid block shivering in patients undergoing elective urological surgeries: an experience
Israr-UL-Haq Lone1, Yasir Bashir2, Ansar-UL-Haq-Lone3, Nusrat Bashir4, Sadat S Ali1, Zahoor A Shah1, Nadeem A Khan1, Mohd A Shah2, Abdul Q Lone2
1 Department of Anesthesiology and Critical Care, Sheri Kashmir Institute of Medical Sciencesm, Srinagar, Jammu and Kashmir, India
2 Department of Critical Care Medicine, Sheri Kashmir Institute of Medical Sciencesm, Srinagar, Jammu and Kashmir, India
3 Department of Orthopaedics, Government Medical College, Srinagar, Jammu and Kashmir, India
4 Laboratory Department of Hematology, Sheri Kashmir Institute of Medical Sciencesm, Srinagar, Jammu and Kashmir, India
|Date of Submission||12-Dec-2014|
|Date of Acceptance||12-Apr-2015|
|Date of Web Publication||29-Jul-2015|
Department of Laboratory Hematology, Sheri Kashmir Institute of Medical Sciences, Soura, Srinagar - 190 011, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
The aim of this study was to investigate the effectiveness of oral clonidine in preventing postsubarachnoid block shivering in urological surgeries.
Patients and methods
It was a prospective double-blind study carried out on 120 elective patients after ethical clearance and after written informed consent was obtained from the patients who underwent urological surgeries.
Patients were divided into two groups of 60 each: the study group and the placebo group. Patients in the study group received an oral clonidine tablet of 150 mg 90 min before block. The severity of shivering and other hemodynamic parameters were noted and compared between the two groups.
We found a statistically significant decrease in postblock shivering incidence as well as severity in the clonidine-treated group, with no significant changes in hemodynamic and other parameters between the two groups and thus recommend its use.
As a prophylaxis, clonidine given orally at a dose of 150 mg seems to be a cheap, effective, and easily available drug for preventing postsubarachnoid block shivering in patients undergoing elective urological surgeries.
Keywords: clonidine, shivering, subarachnoid block
|How to cite this article:|
Lone IU, Bashir Y, AU, Bashir N, Ali SS, Shah ZA, Khan NA, Shah MA, Lone AQ. Role of oral clonidine in preventing postsubarachnoid block shivering in patients undergoing elective urological surgeries: an experience
. Ain-Shams J Anaesthesiol 2015;8:407-12
|How to cite this URL:|
Lone IU, Bashir Y, AU, Bashir N, Ali SS, Shah ZA, Khan NA, Shah MA, Lone AQ. Role of oral clonidine in preventing postsubarachnoid block shivering in patients undergoing elective urological surgeries: an experience
. Ain-Shams J Anaesthesiol [serial online] 2015 [cited 2022 Jan 23];8:407-12. Available from: http://www.asja.eg.net/text.asp?2015/8/3/407/159006
| Introduction|| |
Santiro discovered the clinical value of temperature in 1646, but it took two centuries more before Wunderlich recognized body temperature as a key parameter  . Inadvertent hypothermia is associated with numerous adverse outcomes during the postoperative period. Shivering is an important complication of hypothermia. It is a complicated response of the body and includes at least three different patterns of muscular activity  . It occurs frequently in 40-60% of patients after volatile anesthetics and regional anesthesia, and it remains poorly understood. Although the obvious etiology is said to be cold induced, some types of shivering such as tremors are not thermoregulatory. Shivering may induce arterial hypoxemia, lactic acidosis, and increased intracranial and intraocular pressure and interferes with ECG monitoring, pulse rate, and blood pressure  . It is associated with morbid myocardial outcomes  and increased oxygen consumption up to 200-500%  . The processes that lead to core hypothermia in regional and general anesthesia are similar  . As in general anesthesia, the initial hypothermia in regional anesthesia results from redistribution of body heat from the core to the periphery  . Patients given spinal or epidural anesthetics cannot re-establish core temperature equilibrium because peripheral vasoconstriction remains impaired. Shivering in these patients produces little amount of heat, because it is restricted to the small muscle mass cephalad to the block. Shivering is associated with substantial adrenergic activation and discomfort. Some patients find accompanying cold sensations worse than surgical pain. Potent antishivering properties have been attributed to numerous drugs. These drugs belong to several classes, and include biogenic monoamines, cholinomimetics, cations, endogenous peptides, and N-methyl-d-aspartate receptor antagonists. All these appear to modulate central thermoregulatory control mechanisms.
Clonidine is a selective partial α2 adrenergic receptor agonist, which has both central and peripheral effects. This drug is primarily used as an antihypertensive agent, but also has sedative and analgesic properties. Clonidine stops shivering. It synchronously decreases the cold response threshold while slightly increasing the sweating threshold , , thus suggesting that it acts on the central thermoregulatory system rather than preventing shivering peripherally  .
| Patients and methods|| |
The study was carried out in the Department of Anesthesiology and Critical Care, Sheri Kashmir Institute of Medical Sciences, Srinagar, over a period of 2 years from October 2010 to October 2012 in a prospective randomized double-blind manner after taking ethical clearance. Written informed consent was obtained from 120 adult patients. The patients included in the study were of ASA physical status I and II, aged more than 20 years, and were undergoing elective urological procedures under subarachnoid. Patients in the study were randomized to receive either clonidine 150 μg tablet orally (n = 60) or placebo tablet (n = 60) 90 min before subarachnoid block in a double-blind manner. The person who administered the drug was kept blinded to the study. The method of randomization used was simple randomization without replacement.
Patients with history of allergic reaction to local anesthetic, clonidine, bleeding diathesis, pre-existing neurological or spinal disease, bradycardia [heart rate (HR) <50 beats/min on preoperative ECG], hypotension [systolic blood pressure (SBP) <100 mmHg], severe atrio-ventricular (AV) conduction block, or renal insufficiency were excluded from the study.
Preanesthetic examination and medication
A day before surgery preanesthetic visit was made and detailed history and thorough medical examination was carried out. Patients were made to fast and were sedated with tablet alprazolam 0.25 mg on the previous night. On arrival to the operation room intravenous line was established and monitoring of ECG, saturation, and noninvasive blood pressure was carried out for routine purposes. Patients were allocated into two groups. Group 1, the study group, included 60 patients who received tablet clonidine, and group 2, the control group, included 60 patients who received tablet placebo 90 min before surgery in double-blind manner. Preloading of both groups was performed with 1.5 l of dextrose normal saline. A subarachnoid block up to the level of T 9 -T 10 dermatome was achieved with 2.5-3 ml (12.5-15 mg) of 0.5% of heavy bupivacaine injected into the L 3 -L 4 intervertebral space using a 25 G Quincke's spinal needle after taking all aseptic precautions. Block was performed in the sitting position in all surgeries. The temperature in the operation theater was maintained at around 22 ± 1°C. ECG, SpO 2 , and noninvasive blood pressure were monitored regularly. Core body temperature was monitored by placing tympanic membrane probe. Shivering if occurred was treated in the same way in both groups, with an injection of pethidine 25 mg intravenously. Bradycardia (HR <50 bpm) was treated with an injection of atropine 0.6 mg intravenously. Hypotension (SBP <100 mmHg) was treated with rapid infusion of fluids in the head down position and incremental doses of injection ephedrine 6 mg intravenously. Any unusual event and drug treatment, which we encountered during operation and in postanesthesia care room, were recorded.
The assessment, as far as shivering is concerned, was made by an observer during three periods - that is, 15 min after subarachnoid block, therewith until the end of procedure, and in the postanesthesia care room for a period of 1 h at an interval of 15 min. The intensity of shivering was graded as follows:
None: no perceptible tension of muscles.
Mild: slight muscle tonus (masseter muscle).
Moderate: real shivering (proximal muscle).
Severe: Generalized shivering (whole body).
Statistical analysis of the data was performed using the χ2 -test for nominal data and Student's t-test was used for quantitative data. These tests were two-tailed and were referenced for P-values for their significance. Any P-value less than 0.05 was taken as statistically significant. The analysis was carried out using statistical package for social science (IBM SPSS statistics 200, Delhi, India) for Windows.
| Results|| |
On comparison of these variables (i.e. age, weight, sex, and ASA status) no statistically significant difference was found between the two groups. Both groups were comparable with respect to age, weight, sex, and ASA status [Table 1] and [Figure 1].
|Figure 1: Graphical representation of demographic data of group A (clonidine) and group B (placebo ).|
Click here to view
On comparison of baseline and regular interval HR, baseline and regular interval SBP, and tympanic temperature between the two groups, no statistically significant difference was found (P > 0.05).
Shivering was present in only 5% of patients who were given clonidine, whereas in the placebo group shivering was present in 16.6% of patients. The difference was statistically significant (P < 0.05) at 15 min after subarachnoid block. It was more common in group B patients at 30, 45, and 90 min after block (P < 0.05). At 60 min after block, four (6.7%) patients in group B developed shivering compared with two patients in group A; however, the difference was statistically nonsignificant (P > 0.05) [Table 2] and [Figure 2].
When the grades of shivering between the two groups were compared, a statistically significant difference between the two groups was observed [Table 3] and [Figure 3].
Six patients in group A needed atropine for bradycardia compared with seven patients in group B (statistically nonsignificant). Ephedrine for hypotension was given to eight patients in the study group compared with six patients in the placebo group (statistically nonsignificant).
No significant difference with regard to nausea and vomiting was found between the two groups (P = 0.64).
| Discussion|| |
Shivering is very unpleasant and a physiologically stressful condition. It induces arterial hypoxemia, lactic acidosis, and increases intraocular and intracranial pressures and interferes with ECG monitoring, pulse rate, and blood pressure , . It may also cause complications, especially in patients with coronary artery disease, because of associated increase in oxygen consumption by 100-600%, cardiac output, CO 2 production, and circulating catecholamine's and a significant decrease in mixed venous oxygen saturation , .
Various drugs have been investigated for the prevention or treatment of shivering, such as pethedine, clonidine, tramadol, nefopam, doxapram, ketanserin, fentanyl, and methylphenidate, which are simple, cost-effective, and easily available. Among the pharmacological agents, clonidine has been shown to be one of the most cost-effective treatments. This drug is primarily used as an antihypertensive agent but also has sedative and analgesic properties. Clonidine is an established antishivering drug , . The antishivering effects of α-adrenoceptor agonists are mediated by binding to α2 receptors, mainly the α2b receptors that mediate vasoconstriction and the antishivering effect  . In addition, clonidine has hypothalamic thermoregulatory effects  , as it may exert an inhibitory action on the hypothalamus by decreasing the noradrenaline synaptic release through α2 receptors located at the presynaptic nerve terminals, thus contributing to its antishivering effects  .
The present study was undertaken to study and evaluate the efficacy of oral clonidine in preventing postsubarachnoid block shivering in patients undergoing elective urological surgeries.
The study involved 120 patients (ASA class I and II) of either sex who were randomly allocated into two groups of 60 each. Group A received tab clonidine 150 μg 90 min before procedure. Group B received tablet placebo 90 min before procedure. The following parameters were recorded and compared between the two groups:
Selected patients were 20 years or older, and all patients had undergone surgeries under spinal anesthesia. The groups were comparable with respect to demographic factors (age, weight, sex, and ASA status).
- Hemodynamic parameters (HR, blood pressure, and saturation).
- Tympanic temperature at entry in the operation theater, immediately after subarachnoid block therewith until the end of the procedure, and in the postanesthetic room.
- Side effects.
The following parameters were compared between group A and group B.
HR SBP and diastolic blood pressure were recorded at regular intervals between the two groups. On comparison of the HR between the two groups, no statistically significant difference was found (P > 0.05).
This result is in accordance with the study conducted by Sia in 1998, in which they concluded that preventive use of intravenous clonidine 1 μg/kg provides a significant reduction in postextradural shivering without clinically relevant adverse side effects such as hypotension and bradycardia.
SBP and diastolic blood pressure were recorded at regular intervals. There was no statistically significant difference found between the two groups (P > 0.05).
This is in accordance with the studies conducted by Stapelfeldt et al.  and Buggy et al.  , which showed no statistically significant difference in hemodynamic parameters between the clonidine and placebo groups.
Tympanic membrane temperature
Tympanic membrane temperature was recorded intraoperatively and postoperatively, and the results were comparable between the two groups. Results did not show any statistically significant difference between the two groups (P > 0.05).
This was comparable to that reported in the study conducted by Buggy et al.  , in which they found that clonidine at induction reduces shivering after general anesthesia. A study conducted by Horn et al.  also showed no significant difference as regards core temperature between the clonidine and placebo groups.
Shivering was compared between the two groups at arrival in the operation theater, 15 min after subarachnoid block, 30 min after subarachnoid block, and in the postanesthesia care unit for a period of 1 h. The incidence of postsubarachnoid block shivering in the clonidine group was significantly lower than that in the placebo group. Shivering was present only in 5% of cases in group A at 15 min after subarachnoid block, but it was 16.67% in group B. At 30 min after subarachnoid block, 3.3% of patients from group A had shivering, whereas it was 15% in group B. At 45 min after subarachnoid block the incidence of shivering was 13.3% in group B versus 3.3% in group A. At 60 and 90 min after subarachnoid block, the incidences of shivering in the placebo group were 6.69 and 13.3% versus 3.3 and 3.3% in the clonidine group, respectively. Of the 11 patients who had shivering in the clonidine group, the intensity of shivering was scaled as mild in five (8.33%) cases, as moderate in the other five (8.33%) cases, and as severe in one (1.67%) case. In the placebo group, of the 39 patients, the intensity of shivering in eight (13.33%) cases was scaled as mild, in 20 (33.33%) cases as moderate, and in 11 (18.33%) cases as severe. In our study we found that clonidine seems to be a useful drug in the prevention of shivering. The results in our study are in agreement with that reported in the study conducted by Tewari et al.  , in which they found that prophylaxis with oral clonidine prevents perioperative shivering in patients undergoing transurethral resection of prostate without cardiovascular side effects. In our study, the incidence of shivering was 65% in the placebo group, which was in a proportion similar to that reported in the study conducted by Tewari et al.  .
Mohammadi and Seydi  concluded that oral clonidine as premedication reduced the incidence and severity of postanesthetic shivering after general anesthesia.
Our results are also in accordance with those reported in the studies conducted by Aidim and Anssari  , Horn et al.  , Bansal and Jain  , Bilotta et al.  , Dhorigol et al.  . In all these studies they concluded that clonidine reduces the incidence and severity of shivering in both general and regional anesthesia.
The patients from the two groups were observed for hypotension, bradycardia, nausea, and vomiting. Only six patients in group A developed bradycardia. However, in group B seven patients developed bradycardia, which was statistically nonsignificant (P > 0.05). A total of eight patients in group A had hypotension, whereas in group B six patients had hypertension. Nausea and vomiting were seen only in three patients in group A and in two patients in group B.
| Conclusion|| |
As a prophylaxis, clonidine given orally at a dose of 150 μg seems to be a cheap, effective, and easily available drug for preventing postsubarachnoid block shivering in patients undergoing elective urological surgeries.
| Acknowledgements|| |
Conflicts of interest
| References|| |
Bhattacharya PK, Bhattacharya L, Jain RK, Agarwal RC. Post anaesthesia shivering (PAS): a review. Indian J Anaesth 2003; 47:88-93.
Sessler DI, Rubinstein EH, Mayeri A. Physiological response to mild perianesthetic hypothermia in humans. Anesthesiology 1991; 75:594-610.
Mahajan RP, Grover VK, Sharma SL, Singh H. Intraocular pressure changes during muscular hyperactivity after general anesthesia. Anesthesiology 1987; 66:419-421.
Frank SM, Fleisher LA, Breslow MJ, Higgins MS, Olson KF, Kelly S, Beattie C. Perioperative maintenance of normothermia reduces the incidence of morbid cardiac events. A randomized clinical trial. JAMA 1997; 277:1127-1134.
Bay J, Nunn JF, Prys-Roberts C. Factors influencing arterial PO2 during recovery from anaesthesia. Br J Anaesth 1968; 40:398-407.
Bredahl C, Hindsholm KB, Frandsen PC. Changes in body heat during hip fracture surgery: a comparison of spinal analgesia and general anaesthesia. Acta Anaesthesiol Scand 1991; 35:548-552.
Matsukawa T, Sessler DI, Christensen R, ozaki M, Schroeder M. Heat flow and distributions during epidural anesthesia. Anesthesiology 1995; 83:961-967.
Delaunay L, Bonnet F, Liu N, Beydon L, Catoire P, Sessler DI. Clonidine comparably decreases the thermoregulatory thresholds for vasoconstriction and shivering in humans. Anesthesiology 1993; 79:470-474.
Delaunay L, Herail T, Sessler DI, Lienhart A, Bonnet F. Clonidine increases the sweating threshold, but does not reduce the gain of sweating. Anesth Analg 1996; 83:844-848.
De Witte J, Sessler DI. Perioperative shivering: physiology and pharmacology. Anesthesiology 2002; 96:467-484.
Sessler DI. Temperature monitoring. In: Miller RD, editor. Miller's anesthesia
. 6th ed. Newyork: Elsevier Churchill Livingstone; 2005. 1571-1597.
Katyal S. Tewari A. Shivering: anesthetic considerations. J Anesth Clin Pharmacol 2002; 18:363-376.
Sessler DI, Isreal D, Pozos RS, Pozos M, Rubinstein EH. Spontaneous post-anesthetic tremor does not resemble thermoregulatory shivering. Anesthesiology 1988; 68:843-850.
Vanderstappen I, Vandermeersch E, Vanacker B, Mattheussen M, Herijgers P, Van Aken H. The effect of prophylactic clonidine on postoperative shivering. A large prospective double-blind study. Anaesthesia 1996; 51:351-355.
Piper SN, Röhm KD, Suttner SW, Maleck WH, Kranke P, Bold J. A comparison of nefopam and clonidine for the prevention of post anesthetic shivering. Anesthesia 2004; 59:559-565.
Bansal P, Jain G. Control of shivering with clonidine, butorphanol, and tramadol under spinal anesthesia: a comparative study. Local Reg Anesth 20114:29-34.
Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology 2000; 93:1345-1349.
Shen KZ, Surprenant A. Mechanisms underlying presynaptic inhibition through alpha 2-adrenoceptors in guinea-pig submucosal neurones. J Physiol 1990; 431:609-628.
Stapelfeldt C, Lobo EP, Brown R, Talke PO. Intraoperative clonidine administration to neurosurgical patients. Anesth Analg 2005; 100:226-232.
Buggy D, Higgins P, Moran C, O'Donovan F, McCarroll M. Clonidine at induction reduces shivering after general anaesthesia. Can J Anaesth 1997; 44:263-267.
Horn EP, Werner C, Sessler DI, Steinfath M, Schulte am Esch J. Late intraoperative clonidine administration prevents postanesthetic shivering after total intravenous or volatile anesthesia. Anesth Analg 1997; 84:613-617.
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. J Urol 2006; 22:208-212.
Mohammadi SS, Seydi M. Effect of oral clonidine in preventing postoperative shivering after general anesthesia. Int J Pharmacol 2007; 3:441-443.
Eidy M, Anssari M. Prophylactic effect of the clonidine on the post-operative shivering. Med J Tabris Univ Med Sci (MJTUMS) 2004; 60: 41-44.
Bilotta F, Ferri F, Giovannini F, Pinto G, Rosa G. Nefopam or clonidine in the pharmacologic prevention of shivering in patients undergoing conscious sedation for interventional neuroradiology. Anesthesia 2005; 60:124-128.
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 Anesth Clin Pharmacol 2010; 26:15-18.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]