Postoperative shivering has remained one of the common adverse events in patients recovering from general anesthesia. Furthermore, it is associated with a major deal of discomfort to both the patients and the medical care team. This prospective observational study compared the effectiveness of prophylactic intravenous ketamine 0.5mg/kg and pethidine 0.5mg/kg in elective surgical patients under general anesthesia.
The antishivering effect of pethidine was suggested by several reports. Its antishivering effect pertains to the k- opioid receptor but not due to µ-receptor-mediated. [9, 11, 12], Even though it has been a novel antishivering drug, side effects related to pethidine preclude its utilization in some situations. 
The preventive effect of ketamine for postoperative shivering was realized in many studies. However, its mechanism of action became difficult to predict due to the pharmacological complexity of the drug. The possible speculation for its antishivering effect would be its action on the thermoregulatory center via NMDA antagonism. Inhibition of NE reuptake at the postganglionic fibers by ketamine induces peripheral vasoconstriction which in turn decreases core to peripheral redistribution of heat. [11, 12, 14]
In this study, demographic factors like age, gender, weight, height, ASA physical status, and BMI were all found to be comparable between the two groups; the type and duration of surgery, amount of blood loss and total fluid intake which were considered as risk factors for perioperative hypothermia and shivering , were all comparable between the two groups (p > 0.05).
In this study, the overall incidence of postoperative shivering was 32.1%. This rate is higher than the report from the study conducted in Isfahan University of Medical Sciences, Iran, by Zabareh SMHT et al. In their study, the overall shivering rate was 26.7%, which is smaller than the rate of our study. , The cause for this might be a variation in intraoperative and postoperative patient management. Another speculation could be intraoperative use of fentanyl, which also has an anti-shivering effect, and higher operation room ambient temperature in their study.
In this study, the number of shivering patients was 11(28.2%) and 14(35.9 %), p = 0.467 for ketamine and pethidine groups respectively. Although the difference was statistically insignificant, it seems practically a better outcome in favor of ketamine. This finding is in line with the study conducted in India by Dar AM et al. Their study showed no statistically significant difference was found between ketamine and pethidine groups (p > 0.05). , This might be due to the utilization of the same dose of the study drugs. Another study conducted in Mashhad, Iran, by Masomeh et al. also reported pethidine and ketamine can similarly reduce postoperative shivering . Our study results was also supported by a study in Tabriz University of Medical Sciences, Iran, by Eydi M. et al. in 2014. , The results of their study showed that ketamine and pethidine are both equally effective in reducing postoperative shivering. This could be due to a similar study design. Moreover, another study, conducted by Ayatollahi V et al. in Iran has reported a similar finding to our study. Their study reported the prophylactic use of low doses of intravenous ketamine (0.3 or 0.5 mg/kg) was found to be effective to prevent postanesthetic shivering. However, administration of 0.3 mg/kg ketamine lowered the rate of hallucination as compared with 0.5 mg/kg. , This might be related to different drug responses. A prospective RCT conducted in Isfahan University of Medical Sciences, Iran, by Zabareh SMHT et al. reported a contradictory finding in favor of pethidine. They said pethidine seems to be the most appropriate choice for preventing postoperative shivering. ,The differences in the study design could have contributed to this discrepancy.
Another prospective randomized study conducted by Emine Arzu et al. in Hacceteppe University, Turkey, showed ketamine in doses of 0.5–0.75 mg/kg had better reduced postoperative shivering than pethidine. However, ketamine 0.75 mg/kg associated with more hallucinations. , This might be caused by a higher dose of ketamine. Another contradictory result to our findings was reported by the study conducted in Motahari Hospital in Jahrom (Iran), by Zabetian H et al. in 2016. , The possible explanation could be due to the usage of a small dose of ketamine than this study.
The severity of postoperative shivering was compared between the two groups and the difference was not statistically significant (p = 0.874). A randomized double-blind study conducted by Dar AM et al. showed similar findings to this study. The number of patients with grade 1 shivering was 7 and 9 in ketamine and pethidine group, respectively, while 3 patients in each group developed grade shivering. This result is in line with the prospective RCT conducted by Masomeh et al.  In their study, while only one patient in the ketamine group developed grade 1 shivering, no patient has developed either grade 2 or 3 shiverings. However, their finding for the pethidine group was similar to the result of this study. This could be due to the less dose pethidine used to prevent postoperative shivering. This study was also supported by a randomized study conducted by Dar AM et al., which showed the number of patients with grade 1 and 2 shivering were 4 and 3 in both ketamine and pethidine groups respectively (p > 0.05).
Body temperature between the two groups was recorded and compared in the operation theatre and in the PACU and has shown no statistical difference (p > 0.05) except the record at one hour in PACU (p = 0.007). There is no factor discovered for the difference at one hour but might be the patient factor and difference in temperature management protocol in PACU. In this study, the mean axillary temperature was lower during intraoperative time compared to the baseline score in both groups. The drop between the two groups was not significantly different (p > 0.05). There might have a clinical significance for this difference and could be due to anesthetic induced impairment of thermoregulatory center, decreased metabolic heat production, or core to peripheral redistribution of heat, and heat transfer through an exposed surgical wound. Another study conducted by Zabareh et al. also revealed no difference in perioperative body temperature among patients who took ketamine and pethidine. , However, the scores in our results were slightly lower when compared with the values of their study. The probable reason could be due to the controlled room temperature (22-250c) in their study, but our study lacks to control ambient temperature.
In this study, side effects like hallucinations, nausea, and vomiting, duration of PACU stay, and sedation associated with the study drugs were compared between the two groups.
The number of sedated patients was significantly higher in pethidine than ketamine group: 6(15.8%) versus 16(42.1%) for ketamine and pethidine groups respectively, p = 0.012. This could be due to differences in the duration of elimination for ketamine and pethidine. Another difference might be due to the combined effects of pethidine with intraoperative morphine, inhalational anesthetics, and perioperative hypothermia.
In this study, nausea and vomiting were observed among the groups and found to be significantly different, p = 0.025. The possible explanation could be opioid-induced activation of the chemoreceptor trigger zone.
PACU stay time between the groups was found to be comparable (48.85 ± 6.73 and 50.13 ± 5.90 minutes for ketamine and pethidine groups, respectively, p = 0.374). The result of a study conducted in Iran by Ayatollahi et al. revealed the duration of PACU stay for ketamine and pethidine groups was 64.50 ± 1.43 minutes and 56.67 ± 1.27 minutes respectively.  In the same study, the length of PACU stay was 49.37 ± 1.22 minutes and 43.10 ± 1.60 minutes in those who took ketamine 0.3 mg/kg and control group. Thus, PACU stay time in the previous groups was slightly longer. The reason could be attributed to the higher dose of study drugs.
This is the first study in our country; thus it could be an important source of information for clinical researchers. However, the lack of randomization and control for room temperature and the temperature of intravenous fluids in the institution might be the limitation of this study.