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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 17  |  Issue : 2  |  Page : 190-197

Treatment of postoperative shivering after laparoscopic cholecystectomy under general anesthesia: a comparative clinical study


Anesthesia and Intensive Care Department, Faculty of Medicine, Al Azhar University, Cairo, Egypt

Date of Submission08-Apr-2019
Date of Decision25-Apr-2019
Date of Acceptance17-Jun-2019
Date of Web Publication23-Oct-2019

Correspondence Address:
Saeed M Abdallah
Anesthesia and Intensive Care Department, Faculty of Medicine, Al Azhar University, Cairo, 11111
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AZMJ.AZMJ_67_19

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  Abstract 


Background Postanesthesia shivering is one of the common harmful hazards following general anesthesia, especially with laparoscopic surgery. Postoperative shivering may lead to multiple complications, which may happen owing to increased oxygen demands, precipitating in cardiac and neurological ischemia.
Aim This study aims to compare the therapeutic effects of pethidine, ondansetron, and ketamine in preventing postoperative shivering in laparoscopic cholecystectomy under general anesthesia.
Patients and methods In this prospective study, patients aged from 26 to 55 years scheduled for elective laparoscopic cholecystectomy under general anesthesia were included. Patients who developed shivering in the recovery room were randomly divided into three groups: the first group [pethidine (P)] received intravenous pethidine (0.5 mg/kg), the second group [ondansetron (O)] received intravenous ondansetron 8 mg, and the third group [ketamine (K)] received intravenous ketamine (0.25 mg/kg). The frequency and degree of shivering was determined immediately after surgery, 15 min after study drugs administration, and 30 min after study drugs administration. Moreover, hemodynamic changes before and after drug administration and adverse effects of the study drugs were examined.
Results A total of 95 patients who developed postoperative shivering after laparoscopic cholecystectomy were included in this study. No significant difference was found among the groups regarding treatment and grading of shivering in recovery room 15 min after the study drug administration. No significant difference was found among the groups regarding the recurrence of shivering in recovery room 30 min after study drug administration. There is a significant difference in heart rate changes among the three groups and between group K and group O at 10 and 20 min after the administration of study drugs (P<0.05), and heart rate was higher in group K. There is a significant difference in mean arterial blood pressure among the three groups and between group K and group O at 10, 20, and 30 min after the administration of study drugs (P<0.05), and Mean arterial blood pressure (MAP) was higher in group K. There was no significant difference in oxygen saturation and axillary temperature changes among the three groups at all time before and after administration of study drugs (P>0.05). There was a significant difference among groups P, O, and K regarding sedation, hallucination, and nystagmus, being more in group K, but there was no difference among the groups regarding vomiting and itching.
Conclusion The result of this study showed that ondansetron and ketamine effectively managed postoperative shivering with decreased incidence of recurrence of shivering. Ondansetron seems to be the drug to least affect hemodynamics, with less adverse effects than ketamine in comparison with pethidine.

Keywords: general anesthesia, ketamine, laparoscopic cholecystectomy, ondansetron, pethidine, postoperative shivering


How to cite this article:
Abdallah SM. Treatment of postoperative shivering after laparoscopic cholecystectomy under general anesthesia: a comparative clinical study. Al-Azhar Assiut Med J 2019;17:190-7

How to cite this URL:
Abdallah SM. Treatment of postoperative shivering after laparoscopic cholecystectomy under general anesthesia: a comparative clinical study. Al-Azhar Assiut Med J [serial online] 2019 [cited 2019 Dec 8];17:190-7. Available from: http://www.azmj.eg.net/text.asp?2019/17/2/190/269765




  Introduction Top


Postanesthesia shivering (PAS) is spontaneous, involuntary, rhythmic, oscillating, tremor-like muscle hyperactivity that raises metabolic heat production up to 600% after general or regional anesthesia. PAS may cause discomfort to patients, aggravate wound pain by stretching incisions, and increase intracranial and intraocular pressure [1].

Shivering is very unpleasant, physiologically stressful for the patient after surgery, and some patients find the accompanying cold sensation to be worse than the surgical pain. Although the mechanism of shivering is not clear, various hypotheses have been proposed to explain its occurrence [2].

Shivering exist as a thermoregulatory response to hypothermia or muscle activity with tonic or clonic patterns, and various frequencies have been noticed. However, in the postoperative period, muscle activity may be increased even with normothermia, suggesting that mechanisms other than heat loss with subsequent decline in the core temperature contribute to the origin of shivering. These may be uninhibited spinal reflexes, sympathetic overactivity, postoperative pain, adrenal suppression, pyrogen release, and respiratory alkalosis [3],[4].

Shivering increases oxygen consumption, as well as lactic acid carbon dioxide productions, and metabolic rate is by up to 400%. Therefore, shivering may cause problems in patients with low cardiac and pulmonary reserves. The best way to avoid these postoperative shivering events is to prevent increases in metabolic demands and corresponding hemodynamic changes [4].

PAS occurs in 40% of patients recovering from general anesthesia. Most of the times, it is preceded by central hypothermia and peripheral vasoconstriction, indicating that it is almost a thermoregulatory mechanism, which even today is ill understood. Some shivering may not be thermoregulatory, thus making the management of PAS complex. Various measures (pharmacological and nonpharmacological) exist for prevention of postoperative shivering. Despite the availability of various drugs and technologies to prevent shivering, it continues to remain an ongoing problem in the perioperative period [5].

Pethidine is the most frequently used drug for the control of PAS. Its efficacy is reported to be 53–100%. κ-Opioid receptors play an important role in the modulation of postoperative shivering. This explains the greater efficacy of pethidine compared with equi-analgesic doses of µ-receptor agonists such as morphine, fentanyl, alfentanil, and sufentanil [6].

Ondansetron, a 5-TH3 receptor antagonist, is widely used to prevent postoperative nausea and vomiting. 5-TH can affect the body temperature and shivering in rats, as the balance of norepinephrine and 5-hydroxytryptamine (5-HT) in the preoptic-anterior hypothalamus controls the temperature set point [7],[8]. Consistently, several studies [3],[9],[10] have demonstrated that ondansetron can prevent PAS, which makes ondansetron a promising drug for postoperative complications, including PAS, nausea, and vomiting [11],[12],[13].

When ondansetron is used for the prevention of PAS, the hemodynamic profile of the patient does not change, which is beneficial for safety in anesthesia. Furthermore, our review looked at the adverse effects on the cardiovascular system, namely, bradycardia and hypotension [14].

Ketamine, a competitive N-methyl-d-aspartate (NMDA) receptor antagonist, plays a role in thermoregulation at multiple levels of the process. The NMDA receptor modulates noradrenergic and serotoninergic neurons in the locus coeruleus. It is used as an antishivering agent over an intravenous dose range of 0.25–0.75 mg/kg; however, even at these doses, it causes adverse effects including drowsiness, hallucination, and delirium [15].

Many drugs are used for treating PAS. We chose to compare ondansetron and ketamine with pethidine, which is the most widely used drug for the prevention and treatment of PAS.

Regarding the objectives of this study, the primary outcome is to evaluate the efficacy of ondansetron and ketamine in comparison with pethidine to control postoperative shivering in patients undergoing laparoscopic cholecystectomy under general anesthesia, whereas the secondary outcome was to determine which of these pharmacological interventions has less adverse effects such as sedation, hallucination, itching, vomiting, and nystagmus.


  Patients and methods Top


After obtaining approval of the Ethics Committee of Department of Anesthesia and Intensive Care, Faculty of Medicine, Al Azhar University, Cairo, Egypt, and informed written consent from the patients, this prospective double-blind randomized control clinical trial was conducted from September 2017 to November 2018 in AL-Hussien and Sayed Galal Hospitals, Cairo, Egypt.

Patients scheduled for laparoscopic cholecystectomy during this period were chosen for the study. Patient with fever or allergy to any of the study drug, patients with any history of neuromuscular abnormality, those who had received vasoconstrictors and adrenergic agonists on medical records, those with past history of convulsions, patients who received cold fluids (fluids without warming) and massive blood transfusion (≥3 U transfusions or blood loss>50% of total blood volume intraoperatively), those who had temperature less than 36.5°C at extubation, and those with age less than 21 years old or more than 56 years old were excluded.

According to the estimated sample size, only 95 among the patients who developed postoperative shivering of grades 2, 3, and 4 ([Table 1]), of either sex, and matched the study inclusion criteria (ASA I and II classification), undergoing laparoscopic cholecystectomy under general anesthesia, were included and randomly divided by computer-generated and sealed opaque envelops into three groups postoperatively: the first group [pethidine (P)] included 32 patients who received intravenous pethidine (0.5 mg/kg), the second group [ondansetron (O)] included 31 patients who received intravenous ondansetron 8 mg, and the third group [ketamine (K)] included 32 patients who received intravenous ketamine (0.25 mg/kg). One patient was excluded from the study after he developed hypothermia (<36°C).
Table 1 Grading system for severity score of postanesthesia shivering [11]

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Anesthesia technique was standardized using propofol 2 mg/kg, atracurium 0.5 mg/kg, fentanyl (1–2 µg/kg), and isoflorane 2% with oxygen. The trachea of all the patients was intubated with an endotracheal tube, and then maintenance of anesthesia was done by isoflurane 1.2%; atracurium and atropine (0.01 mg/kg) and neostigmine (0.02 mg/kg) were used at the end of operation for neuromuscular blockade antagonization. Ringer lactate was used for intraoperative fluid management, and operating room temperature was kept at 22°C. Basic monitoring was done intraoperatively.

All patients in the recovery room received a blanket and oxygen by facial mask (5 l/min) with monitoring of oxygen saturation, heart rate, blood pressure, and axillary temperature every 10 min.

The patients who developed shivering postoperatively of grade 2, 3, or 4 in the recovery room were included in the study. According to the sample size, they were randomly allocated into three groups.

Grade of shivering was assessed by anesthesiologist who was blinded to the drug used. Drugs were made by a anesthetist, not include in this study, in 10-ml syringes. All patients were blinded to the drug used for the control of shivering. Patients in group P were given intravenous pethidine (0.5 mg/kg), patients in group O were given intravenous ondansetron 8 mg, and patients in group K were given intravenous ketamine (0.25 mg/kg). The drugs were given slowly intravenous over 5 min. Shivering grade was evaluated before injection of the study drugs (0 min) and 15 min after study drug administration. Recurrence of shivering was recorded 30 min after study drug administration. Arterial oxygen saturation, heart rate, mean arterial blood pressure, and axillary temperature of all patients were recorded. Among the patients who developed shivering, level of shivering was monitoring before drug administration, and 10, 20, and 30 min after study drug administration. Possible adverse effects associated with the drugs, like itching, vomiting, sedation, nystagmus, and hallucination, were recorded.

Statistical analysis

Data were coded and entered using the statistical package SPSS version 22 (Inc. programes, Chicago, USA). Data were summarized using mean and SD for normally distributed quantitative variables, and comparison between the groups was done using analysis of variance followed by post-hoc test if there is significance. Qualitative data were presented as frequencies (n) and percentages, and χ2-test was used to compare between the three groups. The significance level was set at P value up to 0.05.


  Results Top


Regarding comparison of the demographic data, age, sex, and ASA physical status showed no statistically significant difference among the three groups (P>0.05; [Table 2]).
Table 2 Demographic characteristics

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No significant difference among the study groups was found regarding grading of shivering in recovery room before the study drug administration ([Table 3]).
Table 3 Baseline grade of shivering before the study drug administration

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No significant difference among the study groups was found regarding grading of shivering in recovery room 15 min after study drug administration ([Table 4]).
Table 4 Grade of shivering after 15 min of the study drug administration

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No significant difference among the study groups was found regarding the recurrence of shivering in recovery room 30 min after study drug administration ([Table 5]).
Table 5 Recurrence and grade of shivering after 30 min of the study drug administration

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There is a significant difference in heart rate changes among the three groups and between groups K and O at 10 and 20 min after administration of study drugs (P<0.05), with the heart rate being higher in group K (Graph 1).



There is a significant difference in mean arterial blood pressure among the three groups and between groups K and O at 10, 20 and 30 min after administration of the study drugs (P<0.05), with mean arterial blood pressure (MAP) being higher in group K (Graph 2).



There was no significant difference in axillary temperature changes among the three groups at all times, before and after administration of study drugs (P>0.05; Graph 3).



There was no significant difference in oxygen saturation among the three groups at all times, before and after administration of study drugs (P>0.05; Graph 4).



There was a significant difference among groups P, O, and K regarding sedation, hallucination, and nystagmus, and these three complications were more with group K, but there was no difference among the groups regarding vomiting and itching ([Table 6]).
Table 6 Post-drug administration complications

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  Discussion Top


Shivering continues to be a common problem faced by anesthesiologists during the intraoperative and postoperative period and reported to range from 20 to 70% in general anesthesia procedures. The exact mechanism of development of shivering is not known. Several hypotheses have been raised, which include perioperative hypothermia, pain, postoperative heat loss, and direct effects of certain anesthetics [8].

Shivering increases oxygen consumption as much as five-folds, decreases arterial oxygen saturation, and has been shown to correlate with an increased risk of myocardial ischemia, angina, and wound pain. Shivering increases metabolic rate up to 400%. Postoperative shivering may increase the hospital stay and is a common cause of discomfort in patients recovering from anesthesia [9].

It should be noted that shivering following general anesthesia is different to that following neuroaxial anesthesia because general anesthesia only impairs central thermoregulatory control, whereas neuroaxial anesthesia impairs both central and peripheral thermoregulation [4].

In this study, it was found that the three drugs were effective in treatment of postoperative shivering after general anesthesia, and there was no significant difference among the groups regarding the grading of shivering in recovery room 15 min after study drug administration, and also no significant difference among the groups regarding recurrence of shivering in the recovery room 30 min after study drug administration.

Pethidine has a therapeutic effect on postoperative shivering, and its mechanism is likely to be associated with the activation of κ and µ-opioid receptor, acting principally on the central nervous system. Pethidine is the only opioid that is an agonist at both the µ and κ receptors closely related to the pathogenesis of shivering by reducing the shivering threshold [16].

Pethidine is the most common intravenous drug used for treating and preventing shivering, as its equi-analgesic dose is much more efficient than other opioids such as fentanyl, alfentanil, sufentanil, or morphine in preventing shivering [17].

Sharma et al. [10], however, found pethidine to be more effective than tramadol at 10, 15, 20, and 30 min, whereas there was no statistically significant difference at 5 and 25 min after giving the study drugs. Pethidine was associated with more sedation, and tramadol caused significant nausea and vomiting.

Ondansetron is a specific 5-HT3 antagonist that is usually recommended for prevention and treatment of nausea and vomiting during or after surgery. Previous studies have demonstrated that a biological amine found in the brain and spinal cord, serotonin (5-HT), plays a role in neurotransmission, and several studies have confirmed that the serotonergic system plays an important role in the control of PAS by inhibiting effect of serotonin reuptake on the preoptic-anterior hypothalamus region [18].

It should be noted that shivering following general anesthesia is different to that following neuroaxial anesthesia because general anesthesia only impairs central thermoregulatory control whereas neuroaxial anesthesia impairs both central and peripheral thermoregulation [4].

Marashi et al. [19] demonstrated that intravenous ondansetron has a dose-dependent effect and found that ondansetron was associated with a dose-dependent reduction of PAS.

Ebru et al. [20] found ondansetron to be as effective as meperidine in controlling shivering. However, they used ondansetron in a dose of 8 mg.

Entezari et al. [21] have depicted the preventive effect of ondansetron on postoperative shivering after general anesthesia in gynecological surgery.

Powell and Buggy [13] found that prophylactic ondansetron (4 mg) significantly decreased shivering in patients undergoing general anesthesia without significant adverse effects.

According to the meta-analysis by Li et al. [22], treatment with ondansetron is safe and reduces postoperative shivering. This finding encourages the use of ondansetron to prevent postoperative shivering.

Nakasuji et al. [23] demonstrated that low-dose intravenous ketamine during surgery reduces the incidence of postoperative shivering after remifentanil-based anesthesia. They concluded that the preventive effect of ketamine on the development of remifentanil-induced shivering was through a NMDA receptor antagonism during anesthesia.

Dal et al. [24] showed that ketamine 0.5 mg/kg and meperidine (20 mg) were effective in preventing PAS in patients receiving general anesthesia.

A previous study demonstrated that 0.25 mg/kg ketamine and 20 mg meperidine were effective in preventing shivering during the postoperative period [25].

Sagir et al. [26] observed that intravenous ketamine (0.5 mg/kg) effectively prevented shivering during regional anesthesia, with minimal adverse effects.

The prophylactic use of ketamine was effective in preventing shivering during neuraxial anesthesia without causing any major adverse effects [27].

Houssein and Mohamed [28] found that 0.25 mg/kg of ketamine was also as effective as 0.5 mg/kg of ketamine for prevention of postspinal surgery shivering.

In this study, there is a significant difference in heart rate changes among the three groups and between groups K and O at 10 and 20 min after administration of study drugs (P<0.05), with heart rate being higher in group K. Moreover, there is a significant difference in mean arterial blood pressure among three groups and between groups K and O at 10, 20, and 30 min after administration of study drugs (P<0.05), with MAP being higher in group K.

In this study, there is no significant difference in oxygen saturation and axillary temperature changes among the three groups at all times before and after administration of study drugs (P>0.05); the only patient who developed severe hypothermia was excluded from the study.

In this study, there was a significant difference among groups P, O, and K regarding sedation, hallucination, and nystagmus, and these three complications were more with group K. However, there was no difference among the groups regarding vomiting and itching.

Zhao et al. [29] found no difference between ondansetron and pethidine in terms of bradycardia or hypotension. However, when compared with placebo, ondansetron was associated with a lower risk of hypotension, although there was no difference for bradycardia.

Several studies have confirmed that pethidine can cause nausea and vomiting, somnolence, delayed emergence from anesthesia, and respiratory depression when used for PAS [17],[30].


  Conclusion Top


The result of this study showed that ondansetron and ketamine effectively managed (in comparison with pethidine) postoperative shivering after laparoscopic surgery under general anesthesia with decreased incidence of recurrence of shivering. Ondansetron seems to be the drug to least affect hemodynamics with fewer adverse effects than ketamine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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