European Journal of Cardiovascular Medicine

Shivering, characterized by spontaneous, rhythmic, tremor-like muscle activity, occurs as a response to core hypothermia, aiming to increase metabolic heat production. It is a common occurrence, reported in 40% to 70% of patients undergoing abdominal surgery with regional anesthesia[1]. In cases of neuraxial anesthesia, hypothermia and subsequent shivering result from vasodilation and the redistribution of heat from the core to the periphery[1]. Spinal anesthesia disrupts thermoregulation by blocking tonic vasoconstriction below the anesthesia level through sympathetic and somatic neural blockade[2]. Shivering can elevate perioperative heart rate and oxygen consumption by up to five times, increasing metabolic demand by as much as 400%. This heightened demand raises the risk of myocardial ischemia, hypoxia, hypercarbia, and lactic acidosis[3]. Additionally, shivering can complicate the monitoring of electrocardiograms, blood pressure, and oxygen saturation[4]. If left untreated, post-anesthetic shivering may lead to serious complications, including increased wound pain, delayed healing, and hemostatic dysfunction, making it particularly harmful for patients with compromised cardiac and pulmonary reserve[5].

Shivering is particularly prevalent in patients undergoing transurethral resection of the prostate (TURP), likely due to the absorption of large volumes of room-temperature irrigating fluid. This phenomenon poses a significant challenge for urologists, as it can obstruct the surgeon's view of the prostate tissue being resected. Additionally, shivering can lead to injuries to the urethra, bladder, and rectum during the procedure, resulting in prolonged operation times and potentially severe complications[4]. Geriatric patients, who represent a substantial portion of those undergoing TURP, are especially vulnerable to hypothermia-induced shivering under spinal anesthesia[6]. Their lower core body temperatures may fail to trigger the protective autonomic responses typically seen in younger patients. Consequently, shivering can exacerbate existing cardiac risks in this population[3]. Therefore, preventing shivering in these patients is crucial, as it not only complicates intraoperative monitoring but also heightens the likelihood of surgical complications.

Both pharmacological and non-pharmacological methods are employed for the control of shivering[7]. Non pharmacological methods are by external heating with use of warming blankets, forced air warming and warmed fluids but they are cumbersome to use and only partially effective[8]. In pharmacological methods various drugs are being used like pethidine, tramadol, ketamine, clonidine, ondansetron, dexmedetomidine etc[8].

Tramadol, an inhibitor of the re-uptake of serotonin (5- HT) and norepinephrine in the spinal cord is found to influence the thermoregulatory control mechanisms. Intravenous (IV) tramadol has been  successfully used in doses ranging from 0.5mg/Kg to 2mg/Kg, however higher doses are found to be associated with side effects like nausea and vomiting[3].  Ketamine is a non-competitive NMDA receptor antagonist with role in thermoregulation secondary to inhibition of nor- epinephrine uptake and can reduce heat redistribution from core to periphery. IV Ketamine has been used in doses of 0.25mg/Kg and 0.5mg/kg. Both doses of ketamine have been found to be effective to prevent shivering, with some studies showing occurrence of side effects like sedation and psychomimetic effects with higher dose[6]. As various studies have shown contradictory results on effectiveness of prophylactic low doses of tramadol and ketamine, to fill in the gap in showing better prophylactic agents concerning the effectiveness of prevention of post spinal anaesthesia shivering incidence, severity and occurrence of adverse effects the present study was conducted to compare the efficacy of intravenous Tramadol and intravenous ketamine for prevention shivering in patients undergoing TURP under spinal anaesthesia. To study incidence and severity of shivering was the primary objective. To evaluate adverse effects associated with use of study drugs, if any like nausea/vomiting, sedation, hypotension and bradycardia were taken as secondary objectives.

The present prospective, randomized and double blinded comparative study was done in the tertiary care teaching hospital after obtaining informed written consent from patients and approval from Institutional Ethical Committee. Ninety patients aged between 40 and 75years belonging to the American Society of Anesthesiologists-Physical Status I and II and  undergoing TURP under spinal anaesthesia were included in the study. Patients with hypersensitivity or drug allergy to the study drugs, patients who develop shivering prior to administration of these drugs, patients requiring general anaesthesia or sedatives intraoperatively and patients on vasodilators/vasoconstrictors were not studied.

The purpose and protocol of the study was explained to all the patients and informed written consent was obtained for participation in the study. All patients were subjected to complete general physical as well as systemic examination including spine examination prior to surgery. Routine investigations like complete haemogram, bleeding time, clotting time and urine routine examination, blood urea, serum creatinine and serum electrolytes were carried out. Any other relevant investigations like liver function tests were done as and when required. Patients were randomly allocated into one of the three groups (group T, group K and group P) according to computer generated randomisation list.

After arrival in operating room, standard monitoring comprising of Pulse oximetry (SpO2), Electrocardiography (ECG), Non-invasive blood pressure (NIBP) was established. Baseline readings of vital parameters and body temperature were recorded using digital thermometer. Intravenous line was secured with appropriate size intravenous cannula and ringer lactate infusion will be administered. The operation theatre temperature was adjusted to 22-24 degree Celsius for all cases. All IV fluid and drugs were administered at room temperature to all the patients. All patients were given spinal anaesthesia as per standard technique. Then patients were repositioned to supine position and covered with one layer of cotton sheet. Modified Bromage Scale was used for the assessment of spinal anaesthetic block for intended sensory and motor block around T10. Then, study drugs were prepared and administered by fellow anaesthesiologist who is not involved in the study. Group T patients (n=30) received 0.5 mg/kg Tramadol in 10ml normal saline IV infusion over 5 minutes. Group K patients (n=30) received 0.25 mg/kg Ketamine in 10ml normal saline IV infusion over 5 minutes. Whereas Group P patients (n=30) received plain 10ml normal saline IV infusion over 5 minutes. The patient as well as anaesthesiologist involved in the data collection and analysis were blinded to the group allocation. The patient was draped in surgical drapes and then surgery began.

Haemodynamics parameters like Patient’s heart rate(HR), systolic blood pressure(SBP) and diastolic blood pressure(DBP) were recorded alongwith oxygen saturation(spO2) and temperature every 5 minutes intraoperatively and every 10 minutes postoperatively over an hour. Shivering was noted and severity was graded using a five-point scale as outlined by Crossley and Mahajan[9]: Grade 0 :No shivering, Grade 1: One or more of the following: Piloerection, peripheral vasoconstriction, 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. The degree of sedation was noted and graded on a four-point scale described by Filos et al[10]: Grade 1: Awake and alert, Grade 2: Drowsy, responsive to verbal stimuli, Grade 3: Drowsy, arousable to physical stimuli, Grade 4: Unarousable. Any Complications such as nausea, vomiting, bradycardia, or hypotension was recorded and treated accordingly.

The sample size was derived with 80% power of study and 5% level of significance and 95% confidence interval with sample size came out to be 26. We included 30 patients in each group. Hence we recruited 90 patients for the study.

Statistical analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. A p value of <0.05 was considered statistically significant.

A total of 90 patients who underwent TURP under spinal anaesthesia, were studied. The three groups were comparable in terms of demographic data as there were no significant differences in terms of age and ASA grade(Table 1).

Table 1: Demographic data comparison among three groups.

 Both Ketamine and Tramadol were found to be effective to prevent shivering as compared to placebo group. Tramadol group had a statistically lower incidence of shivering than ketamine. [Table2/Fig-1]. Placebo group had maximum number of patients who experienced shivering. Whereas, least number of Tramadol group patients experienced shivering. This result was found to be statistically significant(p value- 0.002).

Table 2: grades of shivering comparison among three groups

Fig.1: grades of shivering comparison among three groups.

Baseline haemodynamic parameters (heart rate, systolic blood pressure, diastolic blood pressure) were found to be comparable among all three groups. The heart rates, on comparison within all the groups, were not found to be statistically significant (p-value >0.05) from the baseline values at any time point. The SBP and DBP showed similar results with no statistically significant difference on comparison within three groups (p-value >0.05). [table 3, Fig.2]

Table 3. Heart rate variation at all time points among three groups.

Fig 2. SBP comparison among three groups at all time points(p value >0.05)

Regarding SpO2, a similar variation was noted among all the three groups (p-value >0.05). all patients in either group maintained SpO2 >95%[Fig-3].

Fig 3. SpO2 variation among three groups.

The incidence of nausea, and vomiting were significantly more in tramadol group as compared to placebo and ketamine group. (p-value =0.002) [Table 4].

Table 4: nausea/ vomiting incidence among patients in all three groups

Post-spinal shivering is a frequent issue encountered during anesthesia and surgical procedures, making its prevention an important aspect of clinical practice. Ketamine and tramadol are two prophylactic agents commonly used to mitigate intraoperative shivering. Various studies have highlighted the effectiveness of pharmacological options such as ketamine, pethidine, and tramadol in preventing post-spinal shivering. Notably, low doses of ketamine and tramadol tend to have fewer adverse effects, such as sedation and hallucinations[11]. However, some research presents conflicting evidence regarding the efficacy of low-dose ketamine and tramadol for this purpose. While higher doses of these medications have proven effective in managing post-spinal shivering, their associated side effects often restrict their use. Our study aimed to compare the effectiveness of low-dose ketamine and tramadol in reducing intraoperative shivering in patients undergoing transurethral resection of the prostate (TURP) under spinal anesthesia

Overall incidence of shivering in present study was found to be 28.8% (26 patients out of total 90), with 15.55% patients experienced grade 3 and 4 shivering. 50% of patients receiving placebo experienced shivering whereas 23.3% patients experienced in ketamine group and only 13.3% patients in tramadol had shivering. It shows that both ketamine and tramadol are effective in prevention of post spinal anaesthesia shivering, however tramadol is more effective agent for this purpose. The conflicting results were found in Gamechu et al’s study[5] where the severity of shivering proportion in grades two and three was much higher in tramadol than in the ketamine group and the over-all distribution of post-spinal shivering was high in the tramadol group. This difference could be due to low dose of ketamine used in the present study. Our study results aligns with a study done by shoura MA et al in 2025[12] to compare ketamine vs tramadol to prevent post spinal shivering in patients undergoing lower limb surgeries,where authors concluded that Tramadol emerged as the more effective prophylactic agent, significantly reducing the occurrence of shivering during surgery and demonstrating favourable outcomes in terms of sedation levels and the impact on cardiovascular and respiratory parameters.

Haemodynamic parameters were comparable in all three groups at all time points. These results were contradictory to findings of study done by Gamechu et al[5] where the authors found that intraoperative hemodynamic parameters had a statistically significant difference in both groups after 20 min with a p-value of less than 0.001 in MAP. The similar results to present study were found by Askari et al[13], with no significant haemodynamic differences among study groups. It may be due to use of room temperature iv fluids and similar operation theatre temperature for all the participants.

Nausea and vomiting was recorded only in tramadol group where 6 patients(20%) experienced nausea and 2 patients (6.7%) had vomiting episode. None of the patients in placebo and ketamine group experienced nausea or vomiting. This finding was similar to results of study by Gamechu et al[5] where tramadol group had maximum incidence of nausea and vomiting. Another study by Sangi S et al[14] showed the similar results where authors found that Ketamine was associated with a lower incidence of nausea, vomiting, and bradycardia but a higher incidence of hallucinations compared to tramadol.

The present study concluded that both Tramadol and Ketamine are effective to prevent post-spinal shivering in patients undergoing TURP. Tramadol is superior agent as prophylaxis against postspinal shivering when compared with 0.25mg/Kg Ketamine without any psychomimetic side effects. However, IV tramadol is also associated with side effects like nausea and vomiting. Furthur studies are required to establish the findings of present study.

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