Shivering is a frequent and unpleasant complication occurring during the perioperative period and is characterized by involuntary, rhythmic contractions of skeletal muscles. The reported incidence of post-anaesthesia shivering ranges between 40–50% in previous study.[1] Although often considered a physiological response to cold exposure, shivering after anaesthesia can significantly increase metabolic demand by elevating oxygen consumption and carbon dioxide production, thereby posing potential risks, particularly in patients with limited cardiopulmonary reserve.[2] The exact mechanism responsible for post-anaesthetic shivering is complex and multifactorial. Several factors contribute to its development, including perioperative heat loss, increased sympathetic activity, pain, and the release of inflammatory mediators or pyrogens.[3] Unlike general anaesthesia, regional anaesthesia preserves hypothalamic thermoregulatory mechanisms; however, spinal anaesthesia may predispose patients to greater heat loss. This occurs due to peripheral vasodilatation, redistribution of core body temperature, reduced muscular activity below the level of blockade, and administration of intravenous fluids at lower temperatures.[4] Post-spinal anaesthesia shivering is not only distressing for patients but may also interfere with intraoperative monitoring and increase physiological stress. The associated rise in oxygen consumption, carbon dioxide production, intraocular pressure, and intracranial pressure can be detrimental in susceptible patients, including those with compromised respiratory function, fixed cardiac output states, or intracranial pathology.[1,2] Management of perioperative shivering includes both non-pharmacological and pharmacological strategies. Non-pharmacological approaches involve active warming techniques such as forced-air warming systems, warming blankets, and administration of warmed intravenous fluids. However, pharmacological therapy remains the mainstay for rapid control of established shivering. A meta-analysis of randomized controlled trials identified clonidine, pethidine, tramadol, nefopam, and ketamine among the commonly used anti-shivering agents.[5] Tramadol, a centrally acting opioid analgesic, has been extensively studied and is widely used for the treatment of post-spinal anaesthesia shivering. Its anti-shivering properties are attributed to opioid receptor activity and modulation of serotonergic and noradrenergic pathways involved in thermoregulation. Despite its effectiveness, tramadol is associated with adverse effects such as nausea, vomiting, dizziness, and sedation, which may limit its clinical acceptability.[6,7] Dexmedetomidine, a highly selective α2-adrenergic receptor agonist and an analogue of clonidine, has gained popularity in anaesthetic practice due to its sedative, analgesic, sympatholytic, and haemodynamic stabilizing properties. It has been shown to reduce the shivering threshold through central thermoregulatory mechanisms and has demonstrated promising anti-shivering effects in previous studies.[8] Several clinical studies have reported that dexmedetomidine effectively prevents and treats post-anaesthetic shivering with acceptable haemodynamic effects and minimal complications. [8-10] Considering the limitations associated with currently available anti-shivering medications and the potential advantages of dexmedetomidine, this study was designed to compare the efficacy, haemodynamic effects, and adverse effect profile of intravenous dexmedetomidine and intravenous tramadol in the treatment of post-spinal anaesthesia shivering.

This prospective, randomized, double-blind comparative study was conducted in the Department of Anaesthesiology, GMC, Latur at a tertiary care teaching hospital. Written informed consent was obtained from all participants before enrolment. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and institutional guidelines. Institutional Ethics Committee approval was obtained (ethics committee approval no (34/IEC/ department of pharmacology/VDGMC/14/07/2023.)., and written informed consent was taken from all participants prior to inclusion in the study . A total of 128 patients of either gender, aged between 18 and 65 years, belonging to American Society of Anesthesiologists (ASA) physical status Grade I and II, undergoing elective or emergency lower abdominal, lower limb orthopaedic, and plastic surgical procedures under spinal anaesthesia were included in the study. Patients with known hypersensitivity to dexmedetomidine or tramadol, significant cardiovascular, pulmonary, renal, or hepatic dysfunction, hyperthyroidism, psychiatric illness, urinary tract infection, uncontrolled diabetes mellitus, autonomic neuropathy, history of substance or alcohol abuse, and those receiving premedication were excluded from the study. All eligible patients who developed post-spinal anaesthesia shivering were included and randomly allocated into two groups using a computer-generated randomization sequence with a 1:1 allocation ratio. Group D received intravenous dexmedetomidine 0.5 µg/kg, whereas Group T received intravenous tramadol 0.5 mg/kg at the onset of shivering. The study drugs were prepared and coded by an independent anaesthesiologist who was not involved in patient management or data collection. The anaesthesiologist administering anaesthesia and the investigator recording the observations were blinded to group allocation. Anaesthetic technique On arrival in the operation theatre, intravenous access was established using an 20G intravenous cannula. Patients were preloaded with Ringer’s lactate solution at 5 mL/kg before spinal anaesthesia, followed by maintenance infusion at 2 mL/kg/hour after establishment of spinal block. Standard monitoring including electrocardiography (ECG), non-invasive blood pressure (NIBP), pulse oximetry (SpO₂), heart rate, and axillary temperature monitoring was initiated, and baseline parameters were recorded. Subarachnoid block was performed under aseptic precautions using 0.5% hyperbaric bupivacaine (15 mg) through a 25G Quincke spinal needle at the L3–L4 or L4–L5 intervertebral space. All operating rooms were maintained at an ambient temperature of 24–25°C. Supplemental oxygen was administered at 2 L/min through nasal prongs. Patients were covered with surgical drapes without active warming measures. Intravenous fluids and anaesthetic medications were administered at room temperature. Heart rate, NIBP, and oxygen saturation were recorded every 5 minutes for the first 30 minutes and subsequently every 15 minutes until completion of the observation period. Continuous ECG monitoring was maintained throughout the procedure. Assessment and treatment of shivering The severity of shivering was assessed using the four-point grading scale described by Wrench et al.[11]: • Grade 0: No shivering • Grade 1: Piloerection, peripheral vasoconstriction, or peripheral cyanosis without visible muscle activity • Grade 2: Visible muscle activity limited to one muscle group • Grade 3: Visible muscle activity involving more than one muscle group • Grade 4: Generalised gross muscle activity involving the whole body Patients who developed Grade 3 or Grade 4 shivering were included in the study and received the assigned study medication as a slow intravenous bolus. The drugs were diluted to a total volume of 5 mL and administered using coded syringes according to the randomization schedule. The onset time of shivering after spinal anaesthesia, severity of shivering, time taken for complete cessation of shivering, and treatment response were recorded. Response was defined as complete disappearance of shivering within 15 minutes following administration of the study drug. Duration of surgery and duration of spinal anaesthesia were documented. Recovery of sensory blockade was assessed using the pin-prick method along with return of spontaneous lower limb movements. Recurrence of shivering during the observation period was noted. Patients with recurrent shivering received an additional rescue dose of the respective study drug (dexmedetomidine 0.5 µg/kg IV or tramadol 0.5 mg/kg IV). Assessment of adverse effects and sedation Adverse effects including nausea, vomiting, bradycardia (heart rate <50 beats/min), hypotension (decrease in systolic blood pressure >20% from baseline), dizziness, and excessive sedation were recorded. Sedation level was assessed using the modified Ramsay sedation score (12): Grade Patient response 1 Awake, anxious, agitated, or restless 2 Awake, cooperative, oriented, and tranquil 3 Awake, responding only to commands 4 Asleep, brisk response to light glabellar tap or loud noise 5 Asleep, sluggish response to light glabellar tap or loud noise 6 Asleep, no response to painful stimulus Sample size calculation: The sample size was calculated based on the difference in mean time for cessation of shivering between dexmedetomidine and tramadol groups reported by Mittal et al.[13]. Considering a two-sided alpha error of 5% and a power of 80%, the minimum required sample size was calculated. To compensate for possible dropouts and exclusions, 64 patients were included in each group, resulting in a total sample size of 128 patients. Statistical Analysis The collected data were entered into a Microsoft Excel spreadsheet and analysed using Statistical Package for Social Sciences for Windows, Version 22. Continuous variables were tested for normality and expressed as mean ± standard deviation (SD). Categorical variables were presented as frequency and percentage. The independent Student’s t-test was used for comparison of normally distributed continuous variables between the two groups, while the Mann–Whitney U test was applied for non-normally distributed data. Categorical variables were analysed using the Chi-square test or Fisher’s exact test wherever appropriate. Repeated measurements of haemodynamic parameters (heart rate, systolic blood pressure, diastolic blood pressure, and oxygen saturation) were analysed using appropriate repeated measures statistical tests. A P value <0.05 was considered statistically significant, and a P value <0.001 was considered highly statistically significant. All statistical tests were two-tailed.

A total of 128 patients were included in the final analysis, with 64 patients allocated to each group. Baseline demographic and clinical characteristics of the study participants are presented in Table 1. The two groups were comparable with respect to age, gender distribution, ASA physical status, and duration of surgery. No statistically significant differences were observed between the groups for age (P=0.59), gender (P=0.59), ASA status (P=0.47), and duration of surgery (P=0.39), indicating adequate baseline comparability. Table/figure 1: Baseline demographic and clinical characteristics of the study participants Parameters Group T Group D P value Age in years 41.5± 9.64 42.38 ±9.0 0.59 Male(%): female(%) 31(48.4%):33(51.6%) 34(53.1%):30(46.9%) 0.59 ASAI(%):ASAII(%) 31(48.4%):33(51.6%) 27(42.2%):37(57.8%) 0.47 Duration of surgery (minutes) 88.36± 26.65 92.27± 24.97 0.39 Data are presented as mean ± standard deviation (SD) or number (percentage). Group T = Tramadol group (n = 64); Group D = Dexmedetomidine group (n = 64). P < 0.05 was considered statistically significant. The characteristics and treatment outcomes related to post-spinal anaesthesia shivering are shown in Table 2. The mean time of onset of shivering after spinal anaesthesia was comparable between the tramadol and dexmedetomidine groups (39.58±11.99 minutes vs 41.84±10.13 minutes, P=0.25). However, the time required for complete cessation of shivering following administration of the study drug was significantly shorter in the dexmedetomidine group compared with the tramadol group (4.84±3.41 minutes vs 9.02±3.88 minutes, P=0.001). The treatment response rate was significantly higher in patients receiving dexmedetomidine (89.1%) compared with tramadol (73.4%) (P=0.024). Additionally, recurrence of shivering was significantly lower in the dexmedetomidine group (7.8%) than in the tramadol group (21.9%) (P=0.025). Table/figure 2: Comparison of shivering characteristics and treatment outcomes between the Tramadol and Dexmedetomidine groups Parameters Group T Group D P value Time of onset of shivering (min) 39.58±11.99 41.84±10.13 0.25 Time for cessation of shivering after medication (min) 9.02±3.88 4.84±3.41 0.001 Response rate (%) 47/64(73.4%) 57/64(89.1%) 0.024 Recurrence rate 14/64(21.9%) 5/64(7.8%) 0.025 Data are presented as mean ± standard deviation (SD) or number (percentage). Group T = Tramadol group (n = 64); Group D = Dexmedetomidine group (n = 64). A P value < 0.05 was considered statistically significant. The comparison of adverse effects between both groups is presented in Table 3. Nausea and vomiting were observed exclusively in the tramadol group, affecting 29.7% and 20.3% of patients, respectively, while no patients in the dexmedetomidine group experienced these complications (P=0.0001). Conversely, dexmedetomidine administration was associated with a higher incidence of bradycardia (21.9%), hypotension with bradycardia (9.4%), and drowsiness (10.9%), whereas none of these events occurred in the tramadol group (P=0.0001). Table/figure3: Comparison of adverse effects and sedation profile between the Tramadol and Dexmedetomidine groups Parameters Group T Group D P value Nausea yes/no 19(29.7%) 0(0%) < 0.001 Vomiting yes/no 13(20.3%) 0(0%) < 0.001 Bradycardia 0(0%) 14(21.9%) < 0.001 Hypotension with bradycardia 0(0%) 6(9.4%) < 0.001 Drowsiness 0(0%) 7(10.9%) < 0.001 Values are expressed as number (%). Chi-square test was applied for categorical variables, and Fisher’s exact test was used wherever expected frequencies were small. A P value <0.05 was considered statistically significant. Hemodynamic parameters are illustrated in subsequent tables/figures. Baseline heart rate, post-spinal anaesthesia heart rate, and heart rate at the onset of shivering were comparable between groups. Following administration of study medications, patients in the dexmedetomidine group showed a significant reduction in pulse rate at 5, 10, and 15 minutes compared with the tramadol group (P<0.001). This finding corresponds with the known sympatholytic effect of dexmedetomidine. Similarly, systolic blood pressure values were comparable between groups at baseline, after spinal anaesthesia, and at shivering onset. However, following drug administration, dexmedetomidine produced a significant reduction in systolic blood pressure at 5, 10, and 15 minutes compared with tramadol (P<0.001). Diastolic blood pressure was also comparable between groups before administration of study medication. After treatment, patients receiving dexmedetomidine demonstrated significantly lower diastolic blood pressure values at 5, 10, and 15 minutes compared with the tramadol group (P<0.001). These haemodynamic changes were consistent with the expected pharmacological action of dexmedetomidine, and no clinically significant instability requiring intervention was observed.

Post-spinal anaesthesia shivering remains one of the common and unpleasant complications encountered during regional anaesthesia. It may cause considerable discomfort to patients and can increase oxygen consumption, carbon dioxide production, catecholamine release, and metabolic demand. The exact pathophysiology of shivering following spinal anaesthesia is complex and multifactorial. It is believed to result from impairment of central thermoregulation, redistribution of heat from the core to peripheral tissues, and exposure-related heat loss. Factors such as age, sensory block height, operating room temperature, intravenous fluid temperature, duration of surgery, and anaesthesia may influence the occurrence of shivering. In the present study, environmental and procedural factors were standardized, with operation theatres maintained at 23–25°C and intravenous fluids and medications administered at room temperature. Furthermore, baseline characteristics including age, gender, ASA physical status, and duration of surgery were comparable between both groups, thereby reducing the possibility of confounding bias. The mechanism of post-anaesthetic shivering involves multiple neurotransmitter pathways, including opioid, α2-adrenergic, serotonergic, and cholinergic systems. Various pharmacological agents such as opioids (pethidine, tramadol, nalbuphine), clonidine, dexmedetomidine, ketamine, propofol, and nefopam have been evaluated for prevention and treatment of shivering. However, adverse effects including sedation, nausea, vomiting, hypotension, hypertension, and respiratory depression limit their routine use, leading to continued search for an effective and safe anti-shivering agent. Tramadol is a centrally acting opioid analgesic that exerts its effects primarily through weak μ-opioid receptor agonism and inhibition of serotonin and noradrenaline reuptake in the descending inhibitory pain pathways. Its anti-shivering effect is attributed to modulation of opioid and monoaminergic pathways involved in thermoregulation [14-16]. Due to its established efficacy, tramadol has been widely studied for the treatment of post-neuraxial anaesthesia shivering. Dexmedetomidine, a highly selective α2-adrenergic receptor agonist, possesses sedative, analgesic, sympatholytic, and anti-shivering properties [17]. The anti-shivering action of dexmedetomidine is mediated through activation of central α2 receptors, which modulate hypothalamic thermoregulatory control and reduce the shivering threshold [18]. It decreases vasoconstriction and shivering thresholds without significantly affecting sweating thresholds, suggesting a central mechanism of action rather than peripheral inhibition [13]. These properties make dexmedetomidine an attractive agent for controlling post-spinal anaesthesia shivering. In the present study, the time of onset of shivering was comparable between the two groups (39.58±11.99 minutes in the tramadol group and 41.84±10.13 minutes in the dexmedetomidine group, P=0.25). This indicates that both groups had similar baseline susceptibility to shivering following spinal anaesthesia. Similar findings were reported by Mittal et al., who observed no significant difference in the onset time of shivering between dexmedetomidine and tramadol groups [13]. However, dexmedetomidine demonstrated superior efficacy in controlling established shivering. The mean time required for cessation of shivering after administration of study drug was significantly shorter in the dexmedetomidine group compared with the tramadol group (4.84±3.41 minutes vs 9.02±3.88 minutes, P=0.001). The response rate was also significantly higher with dexmedetomidine (89.1%) compared with tramadol (73.4%) (P=0.024). These findings suggest that dexmedetomidine provides a faster and more effective suppression of shivering. Similar results were reported by Kundra et al., who found significantly shorter shivering cessation time with dexmedetomidine compared with tramadol (174.12±14.36 seconds vs 277.06±23.37 seconds, P<0.001). [20] The recurrence of shivering following initial control was significantly lower in the dexmedetomidine group compared with the tramadol group (7.8% vs 21.9%, P=0.025). The prolonged suppression of shivering with dexmedetomidine may be attributed to its central thermoregulatory action and longer duration of sympatholytic effect. Mittal et al. also observed lower recurrence rates with dexmedetomidine compared with tramadol (4% vs 8%) [13]. Regarding adverse effects, tramadol was associated with significantly higher incidence of nausea and vomiting compared with dexmedetomidine. In the present study, nausea occurred in 29.7% and vomiting in 20.3% of patients receiving tramadol, whereas no such events were observed in the dexmedetomidine group (P=0.0001). These findings are consistent with previous studies demonstrating increased opioid-related gastrointestinal adverse effects with tramadol [15,16]. Conversely, dexmedetomidine was associated with a higher incidence of bradycardia (21.9%), hypotension with bradycardia (9.4%), and drowsiness (10.9%), which are known consequences of α2-adrenergic agonism. Sedation was more pronounced in patients receiving dexmedetomidine. In the present study, 59.4% of patients in the dexmedetomidine group achieved Grade IV sedation compared with none in the tramadol group, while the majority of tramadol-treated patients remained at Grade II sedation. Although dexmedetomidine produced deeper sedation, it is characterized by arousable and cooperative sedation, which may be advantageous in the perioperative setting. Similar observations regarding moderate sedation with dexmedetomidine were reported by Kundra et al. [20] and Mittal et al.,[13] where patients remained easily responsive despite sedation. Hemodynamic parameters demonstrated significant differences after drug administration. Dexmedetomidine produced a significant reduction in pulse rate, systolic blood pressure, and diastolic blood pressure compared with tramadol at 5, 10, and 15 minutes after treatment. These changes are consistent with the sympatholytic properties of dexmedetomidine. However, values remained within clinically acceptable ranges, and no severe cardiovascular complications were observed. Limitations The present study has certain limitations. First, it was conducted at a single tertiary care centre, which may limit the generalizability of the findings to other settings and patient populations. Second, only patients undergoing spinal anaesthesia were included; therefore, the results may not be directly applicable to patients receiving other forms of anaesthesia. Third, although the study drugs were administered in a blinded manner, the sedative effects of dexmedetomidine may have made complete blinding difficult.

Intravenous dexmedetomidine was found to be more effective than intravenous tramadol for the treatment of post-spinal anaesthesia shivering. Dexmedetomidine resulted in faster cessation of shivering, a higher response rate, and a lower recurrence rate compared with tramadol. Although dexmedetomidine was associated with a higher incidence of sedation, bradycardia, and hypotension, these effects were clinically manageable with appropriate monitoring. Tramadol, despite providing effective shivering control, was associated with a higher incidence of nausea and vomiting. Therefore, dexmedetomidine may be considered a useful alternative to tramadol for the management of post-spinal anaesthesia shivering, particularly when rapid control and reduced opioid-related adverse effects are desired.

1. De Witte J, Sessler DI. Perioperative shivering: Physiology and pharmacology. Anesthesiology. 2002;96:467-84. 2. Bhattacharya P, Bhattacharya L. Postanaesthetic shivering (PAS): A review. Indian J Anaesth. 2003;47:88-93. 3. Crowley LJ, Buggy DJ. Shivering and neuraxial anesthesia. Reg Anesth Pain Med. 2008;33:241-52. 4. Chaturvedi S, Domkondwar G. Control of shivering under regional anaesthesia using tramadol. Asian Arch Anaesthesiol Resusc. 2002;57:491-6. 5. Park SM, Mangat HS, Berger K, Rosengart AJ. Efficacy spectrum of antishivering medications: Meta-analysis of randomized controlled trials. Crit Care Med. 2012;40:3070-82. 6. 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. 7. Reddy VS, Chiruvella S. Clonidine versus tramadol for post spinal shivering during caesarean section: A randomized double blind clinical study. J Obstet Anaesth Crit Care. 2011;1:26-9. 8. Bajwa SJ, Gupta S, Kaur J, Singh A, Parmar S. Reduction in the incidence of shivering with perioperative dexmedetomidine: A randomized prospective study. J Anaesthesiol Clin Pharmacol. 2012;28:86-91. 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. 10. Karaman S, Gunusen I, Ceylan MA, Karaman Y, Cetin EN, Derbent A, et al. Dexmedetomidine infusion prevents postoperative shivering in patients undergoing gynaecologic laparoscopic surgery. Turk J Med Sci. 2013;43:232-7. 11. Wrench IJ. Assessment of postoperative shivering. Anaesthesia. 1990;45(10):868. 12. Ramsay MAE, Savege TM, Simpson BRJ, Goodwin R. Controlled sedation with alphaxalone-alphadolone. Br Med J. 1974;2(5920):656-659 13. Mittal G, Gupta K, Katyal S, Kaushal S. Randomised double-blind comparative study of dexmedetomidine and tramadol for post-spinal anaesthesia shivering. Indian J Anaesth. 2014;58(3):257-262. 14. Lee CR, McTavish D, Sorkin EM. Tramadol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs. 1993;46:313-340. 15. Mathews S, Al Mulla A, Varghese PK, Radim K, Mumtaz S. Postanaesthetic shivering - A new look at tramadol. Anaesthesia. 2002;57:394-398. 16. Tsai YC, Chu KS. A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients. Anesth Analg. 2001;93:1288-1292. 17. Grewal A. Dexmedetomidine: New avenues. J Anaesthesiol Clin Pharmacol. 2011;27:297-302. 18. Bajwa SJ, Bajwa SK, Kaur J, et al. Dexmedetomidine and clonidine in epidural anaesthesia: A comparative evaluation. Indian J Anaesth. 2011;55:116-121. 19. Talke P, Tayefeh F, Sessler DI, et al. Dexmedetomidine does not alter the sweating threshold, but comparably and linearly decreases the vasoconstriction and shivering thresholds. Anesthesiology. 1997;87:835-841. . 20. Kundra TS, Kuthiala G, Shrivastava A, Kaur P. A comparative study on the efficacy of dexmedetomidine and tramadol on post-spinal anesthesia shivering. Saudi J Anaesth. 2017;11(1):2-8.