|Year : 2020 | Volume
| Issue : 2 | Page : 94-100
Comparison of intravenous tramadol and intravenous ketamine for the prevention of post-anaesthetic shivering
Tatiparthi Sriranganath1, Sri Devi Radhapuram2, Mangu Hanumantha Rao2, Sunkesula Shameem2, Aloka Samantaray2, Goduguchintha Dharaniprasad2
1 Department of Anaesthesiology, Simhapuri Hospitals, Nellore, Andhra Pradesh, India
2 Department of Anaesthesiology, Sri Venkateswara Institute of Medical Sciences University, Tirupati, Andhra Pradesh, India
|Date of Submission||29-Apr-2019|
|Date of Decision||15-Oct-2019|
|Date of Acceptance||27-Feb-2020|
|Date of Web Publication||4-Aug-2020|
Mangu Hanumantha Rao
Senior Professor and Dean, Department of Anaesthesiology, Sri Venkateswara Institute of Medical Sciences University, Tirupati 517 507, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
Background: Following general anaesthesia, post-operative shivering, apart from its physiological and haemodynamic effects, has been described as even worse than surgical pain.
Methods: After ethical committee approval and informed consent, ninety patients were subjected to study. They were randomly divided into three groups. Just after intrathecal bupivacaine injection, all patients received prophylactically intravenous drug as normal saline (Group C, n = 30) or ketamine 0.5 mg/kg (Group K, n = 30) or tramadol 2 mg/kg (Group T, no = 30) for shivering. The incidence and degree of shivering and the effectiveness and side effects of ketamine and tramadol in preventing shivering during the post-operative period were recorded.
Results: We compared the efficacy of tramadol and ketamine in the prevention of post-anaesthetic shivering in patients undergoing surgery under GA. The incidence of post-anaesthetic shivering was significantly less with tramadol and ketamine as compared to that of the control group (P < 0.01). Tramadol and ketamine were equally effective in controlling the severity of shivering as compared to that of the control group (P = NS). The prevention of shivering was comparable in the tramadol and ketamine groups (P > 0.05). Patients in the ketamine group had statistically significant sedation at 20 and 30 min compared to the tramadol and control groups (P < 0.05). In this study, we can assume that both intravenous tramadol 2 mg/kg and intravenous ketamine 0.5 mg/kg are highly effective and comparable in the prevention of post-anaesthetic shivering and the possible mechanisms is by lowering of shivering threshold.
Keywords: General anaesthesia, ketamine, shivering, tramadol
|How to cite this article:|
Sriranganath T, Radhapuram SD, Rao MH, Shameem S, Samantaray A, Dharaniprasad G. Comparison of intravenous tramadol and intravenous ketamine for the prevention of post-anaesthetic shivering. J Clin Sci Res 2020;9:94-100
|How to cite this URL:|
Sriranganath T, Radhapuram SD, Rao MH, Shameem S, Samantaray A, Dharaniprasad G. Comparison of intravenous tramadol and intravenous ketamine for the prevention of post-anaesthetic shivering. J Clin Sci Res [serial online] 2020 [cited 2020 Sep 21];9:94-100. Available from: http://www.jcsr.co.in/text.asp?2020/9/2/94/291379
| Introduction|| |
The occurrence of shivering after general anaesthesia (GA) has been recognised for many years and has been variously described as pentothal shakes, halothane shakes, post-operative spasticity, shivering, post-anaesthetic shivering and spontaneous post-anaesthetic tremor.
Post-operative shivering occurs in 5%–65% of patients recovering from GA and in 30% of volunteers undergoing epidural anaesthesia. This may be normal thermoregulatory shivering in response to core hypothermia or may result from the release of cytokines by the surgical procedure. The core temperature usually decreases by 0.5 °C–1.5 °C in the 1st h after induction of anaesthesia. All general anaesthetics markedly impair normal autonomic thermoregulatory control. However, non-thermoregulatory shivering may also occur in normothermic patients in response to certain anaesthetics or post-operative pain.
Anaesthesiologists often encounter adult patients who experience thermal imbalance during surgery. Heat loss during anaesthesia occurs not only because of low environmental temperatures and humidity, but also because of infusion of cold fluids, ventilation with cold gases, exposure of body cavities, absence of muscle movement and subcutaneous vasodilatation. Heat loss leads to hypothermia, which may be responsible for shivering.
Post-operative shivering is very unpleasant and physiologically stressful. It may also cause complications, especially in patients with coronary artery disease, because of associated increases in oxygen consumption (by 100%–600%), cardiac output, carbon dioxide production, circulating catecholamines and a significant decrease in mixed venous oxygen saturation. Moreover, an increase in intracranial and intraocular pressure, interference with monitoring of electrocardiography, blood pressure, increased metabolic rate and lactic acidosis have been described in shivering patients.
Shivering, besides its adverse physiological consequences, makes the patient uncomfortable and therefore, attempts have been made to prevent its occurrence by either pharmacological or non-pharmacological measures.
Equipment to maintain normothermia is effective in preventing shivering, but may be expensive and not practical in all settings. Pharmacological control can be achieved by a variety of drugs. Wide ranges of drugs have been used to either prevent or treat post-anaesthetic shivering. The drugs reported to possess antishivering activity and their possible side effects include; Morphine which has unpredictable response along with respiratory depression; Fentanyl which controls shivering, but recurrence rate is high; Pethidine: which has a high incidence of nausea and vomiting and also has side effects of sedation and respiratory depression; Clonidine and ketanserin: both of which cause decrease in systolic arterial blood pressure; Lignocaine: which has an unpredictable response and ineffective in severe shivering; Amitriptyline which causes anticholinergic side effects; Alfentanil: which requires very high doses to be administered; Physostigmine: which causes increase in heart rate and blood pressure along with vomiting.
Butorphanol is a synthetic opioid with both opioid agonist and antagonist properties. It is a strong analgesic, and its respiratory depression has a ceiling effect.
Tramadol, an atypical central acting opioid, is a 4-phenylpiperidine analogue of codeine. It is a novel analgesic with several antinociceptive effects. It inhibits the reuptake of nor-adrenaline and 5-hydroxy tryptamine-3; both of these mechanisms are also involved in temperature regulation. It has the pharmacodynamic advantage in causing less respiratory depression and sedation.
Ketamine hydrochloride is a rapid acting phencyclidine derivative causing sedation, bronchodilatation, decreased intraoperative awareness and profound somatic analgesia with minimal depression of protective laryngeal and pharyngeal reflexes. However, it also causes catalepsy, increased muscle tone, salivation, mild-to-moderate sympathetic overactivity (cardiovascular stimulation) and unpleasant emergence phenomena. It also inhibits post-operative shivering by modulating thermoregulation at a number of levels.
Hence, the safe pharmacological profile of tramadol and ketamine prompted us to conduct the present study to evaluate the efficacy of intravenous tramadol (2 mg/kg) and intravenous ketamine (0.5 mg/kg) in prophylactic suppression of post-anaesthetic shivering after GA.
| Material and Methods|| |
After obtaining approval from the Institutional Ethics Committee, a prospective, randomised, double-blind study was conducted. Written informed consent was obtained from all the study participants. A computer-generated table of random numbers was used for randomisation. Ninety adult patients of American Society of Anesthesiologists Physical status (ASA) Grade I and II of either sex, aged between 18 and 65 years and scheduled for surgery under GA were subjected to study. They were randomly divided into three groups: Group T received tramadol 2 mg/kg diluted to 10 mL intravenous, Group K received ketamine 0.5 mg/kg diluted to 10 mL intravenous and Group C received 10 mL normal saline as placebo. The treatment drugs were prepared and presented as coded syringes by an anaesthetist who was not involved in the management of patients. The exclusion criteria were any patient with evidence of renal, hepatic, cardiovascular, metabolic, multiple allergies and endocrine dysfunction and patients having infection or sepsis or receiving vasoactive drugs, antidepressants and steroids. Procedures which might require administration of blood or blood products and urological endoscopic operations were also excluded from the study.
The pre-operative investigations consisted of haemoglobin concentration, total leucocyte count, bleeding time, clotting time, urine albumin and sugar, and other relevant specific investigations were indicated.
All patients scheduled for inclusion in the study were given tablet diazepam 5 mg on the previous night. Patients were kept nil by mouth for 8–10 h before surgery. The operating room temperatures were maintained between 21°C and 24°C. Intravenous line was secured in the morning with an 18G intravenous cannula and lactated ringer infusion was started. Patients were premedicated with injection glycopyrrolate 0.005 mg/kg intramuscularly and injection midazolam 0.05 mg/kg intravenously 30 min before surgery.
Anaesthesia was induced intravenously with injection thiopentone sodium 5 mg/kg and injection fentanyl 1 μg/kg, and injection vecuronium 0.12 mg/kg was given intravenously to facilitate tracheal intubation. Anaesthesia was maintained with nitrous oxide in oxygen (40%) and isoflurane. Injection vecuronium bromide, a non-depolarising muscle relaxant, was given when needed. At the start of the wound closure, test drug was given through a 10-mL syringe over a period of 2 min. On return of spontaneous respiration, thorough oropharyngeal suction was done. Residual neuromuscular blockade was reversed using neostigmine 0.05 mg/kg and glycopyrrolate 0.01 mg/kg intravenous slowly over 5 min. On return of reflexes, oropharyngeal suction was done and the trachea was extubated. Patients were oxygenated with 100% oxygen for 5 min after tracheal extubation.
Intraoperative temperature monitoring can be done by core temperature measurements using sensing probes in pulmonary artery, distal oesophagus, nasopharynx and tympanic membrane. These temperatures reflect the core temperature of the body and are reliable during rapid thermal perturbations. In the present study, we used nasopharyngeal temperatures measured by a probe inserted into the nasopharynx. In earlier studies tympanic membrane, rectal, oral, nasopharyngeal, skin surface and axillary temperatures were used.,,,
In the present study, the operating room ambient temperatures were maintained at 21°C–24°C. These were comparable with that reported in various other studies (21 °C–23 °C), (24 °C), (20 °C–22 °C), (21 °C–23 °C) and (22 °C–23 °C).
Intraoperative recordings of pulse, blood pressure, oxygen saturation and nasopharyngeal temperature were taken at baseline, pre-drug, post-drug and post-extubation, and the patients were shifted to the post-anaesthetic care unit covered with cotton blankets and given oxygen via facemask at a rate of flow of 5L/min.
Post-operative assessment was done for 30 min at 0, 10, 20 and 30 min. The post-operative assessment consisted of pulse; blood pressure; respiratory rate; oxygen saturation; nasopharyngeal temperature; presence of severity of shivering and occurrence of side effects such as sedation, nausea, vomiting, respiratory depression (defined as respiratory rate <8 breaths/min), hallucinations and delirium.
The shivering was judged by the Crossley and Mahajan score:,, Grade 0; no shivering, Grade I; mild fasciculation of face and neck, Grade II; visible tremor involving more than one muscle group and Grade III; gross muscular activity involving the entire body. The post-operative sedation was judged as follows: Grade 0, alert; Grade I, arouse to voice; Grade II, arouse with gentle tactile stimulation; Grade III, arouse with vigorous tactile stimulation and Grade IV, no awareness.,
The efficacy of drugs was assessed by the occurrence and severity of shivering, grading of post-operative sedation, changes in cardiorespiratory parameters and occurrence of side effects.
| Results|| |
In the present study, ninety ASA Grade I and Grade II patients (n = 90) of either sex and age between 18 and 65 years were selected and randomly allocated to three groups comprising thirty patients each. The patients were studied to evaluate the efficacy of intravenous tramadol (2 mg/kg), intravenous ketamine (0.5 mg/kg) and normal saline (10 mL) for the prevention of post-anaesthetic shivering under GA.
In the tramadol group (T), the incidence of shivering was 2 (6.7%), 1 (3.3%), 1 (3.3%)and 1 (3.3%) at 0, 10, 20, 30 min, respectively. In the tramadol group (T), the incidence of shivering was 2 (6.7%), 1 (3.3%) and 1 (3.3%) at 0, 10, 20, 30 min, respectively. In the ketamine group (K), shivering was recorded in 2 (6.7%), 2 (6.7%), 3 (10%) and 3 (10%) patients at 0, 10, 20 and 30 min, respectively ([Table 1]).
In the control group (C), 19 (63.3%), 17 (56.6%), 15 (50%) and 19 (63.3%) patients had no shivering at 0, 10, 20 and 30 min, respectively. In the tramadol group (T), 28 (93.3%), 29 (96.6%), 29 (96.6%) and 29 (96.6%) had no shivering at 0, 10, 20 and 30 min, respectively. In the ketamine group (K), 28 (93.3%), 28 (93.3%), 27 (90%) and 27 (90%) patients had no shivering at 0, 10, 20 and 30 min, respectively ([Table 1]).
Thus, prevention of shivering by tramadol and ketamine was highly statistically significant as compared to the control group (P < 0.01). Comparison of tramadol and ketamine groups revealed that prevention is better (96.6%) in tramadol group as compared to ketamine group (91.5%), but this difference was statistically not significant (P > 0.05).
The severity of shivering among the three groups was variable. In the control group (C) 3 (10%) suffered Grade III shivering, 6 (20%) suffered Grade II and 2 (6.7%) suffered Grade I shivering at 0 min recordings. The severity of shivering diminished as the patients rewarmed, and no patient had Grade III shivering at the end of 30 min ([Table 1]).
In the tramadol group (T), only two (6.7%) patients suffered Grade I shivering at 0 min and at 10, 20 and 30 min, one (3.3%) patient had Grade I shivering. Whereas in the ketamine group (K), two (6.7%) patients suffered Grade I shivering at 0 min, and one (3.3%), two (6.7%) and one (3.3%) patients suffered Grade I shivering at 10, 20 and 30 min, respectively. One (3.3%) patient had Grade II shivering at 10 and 20 min and two (6.7%) patients had Grade II shivering at 30 min [Table 1].
Administration of tramadol 2 mg/kg and ketamine 0.5 mg/kg intravenously was equally effective in controlling the severity of shivering as no patient had Grade II or Grade III shivering compared to 3 out of 11 (27.2%) patients having Grade III and 6 out of 11 (54.44%) patients having Grade II shivering in the control group at 0 min.
In the control group (C) 4 patients (13.3%) had no sedation, 16 (53.3%) had Grade I sedation, 8 (26.7%) had Grade II sedation and 2 (6.7%) had Grade III sedation at 0 min. The sedation lessened over the next 30 min and at 30 min, 27 patients (90%) had no sedation and 3 (10%) had Grade I sedation. In the tramadol group (T), 6 patients (20%) had no sedation, 12 (40%) had Grade I sedation, 9 (30%) had Grade II sedation and 3 (10%) had Grade III sedation at 0 min. The sedation diminished over the next 30 min and at 30 min, 26 (86.7%) had no sedation and 4 (13.3%) had Grade I sedation ([Table 2]).
In the ketamine group (K), 1 (3.3%) had no sedation, 11 (36.7%) had Grade I sedation, 15 (50%) had Grade II sedation and 3 (10%) had Grade III sedation at 0 min. Patients had significant sedation at the end of 30 min, with 15 (50%) having no sedation, 12 (40%) having Grade I sedation and 3 (10%) having Grade II sedation.
The sedation scores were comparable at 0 and 10 min in the control, tramadol and ketamine groups, which could be due to the residual effects of the anaesthetic agents administered intraoperatively. However, at 20 and 30 min, patients in the ketamine group had statistically significant sedation as compared to those in the tramadol and control groups (P < 0.05). Tramadol and control groups had comparable sedation scores throughout the study (P > 0.05). No patient in the study had Grade IV sedation.
In the tramadol group (T), the side effects noted were nausea and vomiting in five (16.6%) cases and bradycardia in one (3.3%) case, but no respiratory depression was observed ([Table 3]).
|Table 3: Temperature rerecordings, duration of anaesthesia and side-effects|
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Temperature changes in all the three Groups of T, K and C had comparable baseline temperatures, and a significant decrease in temperatures was recorded in the intraoperative period (P < 0.05). In the recovery room, temperatures gradually increased but did not reach the baseline values even at the end of 30 min. The temperature recordings at 30 min were comparable in the three groups, but shivering was recorded in 11 (36.7%) participants in the control group as compared to 1 (3.3%) and 3 (10%) patients in the tramadol and ketamine groups at 30 min. This suggests that both tramadol and ketamine have no effect on the body temperature, and the possible mechanism of their antishivering properties could be by lowering the shivering threshold itself ([Table 3]).
| Discussion|| |
The study compared the efficacy of IV tramadol and ketamine in the prevention of post-anaesthetic shivering following surgery under GA. It showed that both tramadol and ketamine significantly decreased the incidence and severity of shivering after surgery.
Body temperature is controlled by the hypothalamus which integrates information from the whole body. Approximately 80% of this thermal input is derived from the core body temperature. The hypothalamus coordinates increase in heat production (non-shivering and shivering thermogenesis), as well as increase or decrease in heat loss (by causing cutaneous vasodilatation or vasoconstriction, respectively), as needed to maintain normothermia.
Anaesthesia practice in the present era is dictated by the need to provide maximal patient comfort and maintain body homeostatic mechanisms within the normal limits. This has led to improvised patient monitoring and more focus on the factors affecting perioperative mortality and morbidity. Temperature is now being recognised as a vital parameter beside the now-considered vitals of pulse, blood pressure and respiration.
Hypothermia during anaesthesia is the most common perioperative thermal disturbance. Perioperative mortality is due to anaesthetic impaired thermoregulation and exposure to a cold operating room temperature; there occurs a slow and linear reduction in temperature. Finally, core temperature stabilises and virtually remains unchanged. The fall in temperature varies from 0.5°C to 1.5°C during the 1st h.
In the present study, the operating room ambient temperatures were maintained at 21°C–24°C. These were comparable with results reported in other studies, namely, 21°C–23°C, 24°C, 20°C–22°C, 21°C – 23°C and 22°C–23°C.
Regarding the incidence of shivering in the control group, 11 (36.7%), 13 (43.3%), 15 (50%) and 11 (36.7%) patients shivered in the recovery room at 0, 10, 20 and 30 min, respectively. These findings were comparable with 50%, 48%, 36.7% and 40%, but lower than 60% earlier reports of one study. In the tramadol group (T), the incidence of shivering was 2 (6.7%), 1 (3.3%) and 1 (3.3%) at 0, 10, 20 and 30 min, respectively ([Table 1]). These findings are similar to that reported in another study where the incidence of shivering was 2% with 2 mg/kg of tramadol and 4% with 1 mg/kg tramadol. In the ketamine group (K), shivering was recorded in 2 (6.7%), 2 (6.7%), 3 (10%) and 3 (10%) patients at 0, 10, 20 and 30 min respectively. These findings are similar to that reported in another study where it was reported that 0 (0%), 1 (3.3%), 2 (6.7%) and 2 (6.7%) patients had shivering following administration of ketamine 0.5 mg/kg at 0, 10, 20 and 30 min, respectively.
The prevention of shivering by tramadol was comparable to that recorded in other studies (98%), and (100%), The recordings were higher than those reported in another study (80%). In this study tramadol was used at a dose of 1 mg/kg as compared to 2 mg/kg in the present study.
Tramadol and ketamine have no effect on the body temperature, and the possible mechanism of their antishivering properties could be by lowering the shivering threshold itself. These findings were comparable with other report where no relationship between the occurrence and grade of shivering and changes in patient's temperature in the recovery room was documented. A study reported that tramadol decreases sweating, vasoconstriction and shivering thresholds. Another study recorded that patients developing post-anaesthetic shivering experience increased body temperature at the same rate as those who do not develop post-anaesthetic shivering.
In the present study, we compared the efficacy of tramadol and ketamine in the prevention of post-anaesthetic shivering in patients undergoing surgery under GA. The incidence of post-anaesthetic shivering was significantly less with tramadol and ketamine as compared to those of control group (P < 0.01). Tramadol and ketamine were equally effective in controlling the severity of shivering as compared to those of control group (P = NS). The prevention of shivering was comparable in the tramadol and ketamine groups (P > 0.05). Patients in the ketamine group had statistically significant sedation at 20 and 30 min compared to those of tramadol and control groups (P < 0.05). To conclude, tramadol 2 mg/kg or ketamine 0.5 mg/kg administered at wound closure can effectively and safely prevent post-anaesthetic shivering. If prophylaxis for nausea and vomiting is supplemented, tramadol is a potent and better antishivering agent devoid of any sedation compared to ketamine.
Financial support and sponsorship
This study was funded by SVIMS University and Teaching Hospital.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3]