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AMBULATORY ANESTHESIOLOGY

The Efficacy of Ketamine for the Treatment of Postoperative Shivering

From the Department of Anesthesiology and Reanimation, Hacettepe University School of Medicine, Ankara, Turkey.

Address correspondence and reprint requests to Didem Dal, MD, Department of Anesthesiology and Reanimation, Hacettepe University, 06100 Ankara, Turkey. Address e-mail to didemdal{at}yahoo.com.

Abstract

BACKGROUND: There are few reports on the utility of ketamine for the prevention of postoperative shivering. We thus established the efficacy of two doses of ketamine compared with meperidine for the treatment of postoperative shivering.

METHODS: This is a prospective, randomized double-blind study involving 90 ASA I–II patients after general anesthesia. Patients with shivering grade 3–4 were allocated to receive either meperidine 25 mg, ketamine 0.5 mg/kg, or ketamine 0.75 mg/kg IV. Shivering and side effects were monitored at set time intervals.

RESULTS: Shivering grades for the first 4 min after treatment were lower in the ketamine groups; however, nystagmus and feeling like "walking in space" was experienced with both doses of ketamine.

CONCLUSION: Ketamine 0.5–0.75 mg/kg is more rapid than meperidine (25 mg) for the reduction of postoperative shivering, but the side effect profile may limit its usefulness.

Meperidine is commonly used for the treatment of postoperative shivering, a frequent problem in patients recovering from general anesthesia.1–3 It has been reported that prophylactic ketamine 0.5 mg/kg, a N-methyl-d-aspartate receptor antagonist, can be an alternative to meperidine for preventing postoperative shivering.4,5 The aim of this study was to compare the efficacy of 0.5 mg/kg and a higher dose, 0.75 mg/kg of IV ketamine with meperidine 25 mg for the treatment of postoperative shivering after general anesthesia.

METHODS

This prospective, randomized, double-blind study was performed after approval by our Ethics Committee. We obtained informed consent from 489 ASA class I or II patients who had undergone elective abdominal, orthopedic, and plastic surgery under general anesthesia to achieve a recruitment of 90 study patients. In all patients, 1–2 µg/kg fentanyl and 3 mg/kg propofol were used at induction of anesthesia and residual neuromuscular blockade was antagonized using neostigmine 1.5 mg and atropine 0.5 mg at the end of surgery. The ambient temperature in operating room was set at 22°C. During surgery, skin surface and IV fluid warming were not used. Tympanic membrane temperatures were measured using a First Temp Genius Model 3000 A aural canal thermometer (Sherwood Medical Company, St. Louis). Postoperative shivering in the recovery room was graded between 0 and 4.6 Ninety patients, who developed grade 3–4 shivering in the recovery room, were included in the study. Patients who received blood products or metoclopromide, Body Mass Index >30 kg/m², and those with a history of convulsions, multiple allergies, hypertension, coronary artery disease, other cardiorespiratory or neuromuscular pathology were excluded from the study.

The ambient temperature in the recovery room was maintained at 22°C. In the recovery room, all patients were covered with a standard cotton blanket, none of them was warmed actively and all received 4 L/min oxygen by facemask.

The patients were randomly (envelope randomization) allocated to receive meperidine 25 mg (group meperidine, n = 30) or ketamine 0.5 mg/kg (group ketamine 0.5, n = 30) and ketamine 0.75 mg/kg (group ketamine 0.75, n = 30) IV. The treatment drugs were diluted to a volume of 2 mL and presented as coded syringes by an anesthesiologist who was not involved in the management of the patients or in grading of the patients' shivering.

The shivering grade was assessed before (time 0) and every subsequent 1 min after treatment for 10 min. At the end of 10 min after injection, the patients who continued to be assessed with a shivering grade 3 or 4 were treated with meperidine 25 mg IV and this additional drug dosing was recorded. The patient's oxygen saturation, heart rate, and noninvasive arterial blood pressure were recorded before and every subsequent 1 min after treatment for 10 min. Tympanic temperature was measured immediately before the treatment was administered (time 0) and at 5 and 10 min (time 5 and 10) after the treatment was administered. Side effects that may have been related to the study drugs (i.e., nausea, vomiting, hypotension, hypertension, tachycardia, nystagmus, feeling like walking in the space, and hallucinations) and a sedation score (using a five-point scale) were also recorded.

Statistical analysis was performed using Statistical Package for Social Sciences windows version 10.0. The Kolmogorov-Smirnof test, analysis of variance (ANOVA) test, ² test, repeated measures ANOVA test, Student's t-test, Mann–Whitney U-test, and Friedman test were used for statistical analyses. A value of P < 0.05 was considered statistically significant. Post hoc comparisons were performed with Bonferroni correction of the significance level.

RESULTS

The demographics and clinical characteristics were similar among the three groups (Table 1).

There were no statistically significant differences among groups for tympanic temperatures at the 0th, 5th, and 10th min of the study (P = 0.587).

The shivering grade for patients were greater in group meperidine when compared with group ketamine 0.5 and group ketamine 0.75 during the first 4 min after administration of the study drug (Table 2).

Nystagmus and feeling like walking in the space were experienced more frequently in groups ketamine 0.5 and ketamine 0.75 (P = 0.001 and P < 0.001, respectively) compared with group meperidine. Nystagmus was observed in six (20%) patients in group ketamine 0.5 and in nine (30%) patients in group ketamine 0.75 (P > 0.05). Feeling like walking in space was reported in six (20%) patients in group ketamine 0.5 and in 12 (40%) patients in group ketamine 0.75 (P > 0.05). None of the patients had hallucinations or delirium. Despite the treatment of shivering with the study drugs, three patients from each group had shivering grade 3 or 4 at the end of 10 min and therefore were treated with meperidine 25 mg IV. After this additional dose, shivering stopped in all patients. The incidence of nausea and vomiting, oxygen saturation, mean arterial blood pressure, and heart rate for patients were similar among the groups during the study period (P > 0.05).

The higher dose of ketamine produced higher sedation scores for patients at the 10th and 30th min (P = 0.014 and P = 0.032, respectively) (Table 3).

DISCUSSION

In this study, our results indicate that ketamine had a more rapid onset than meperidine for treating postoperative shivering during the initial 4 min after administration. Side effects from ketamine were more commonly observed with the higher dose of ketamine, but the difference did not reach statistical significance. The higher dose of ketamine was also associated with sedation. These side effects were not observed in our previous study in which we used ketamine 0.5 mg/kg approximately 20 min before completion of surgery under general anesthesia.4 This lack of side effects in our previous study may be explained by the short duration of action of ketamine and/or because the side effects for ketamine were masked by the effect of general anesthesia.

There is only one other report on the use of ketamine for the treatment of postoperative shivering.7 The authors also report that ketamine 0.5 mg/kg IV was effective for the treatment of postoperative shivering.7 However, this study was not double-blind and it had no positive control The authors also reported that two patients had developed hallucinations and four patients had developed delirium.7 We did not observe hallucinations or delirium in any of our patients, however, these are well-known side effects of ketamine.

We did not include a control group in our study because we considered it unethical to leave shivering untreated; however, this may be considered a limitation of this study. The doses of ketamine used in this study were rather arbitrary. We had previously shown 0.5 mg/kg was effective for prophylaxis. We also chose a higher dose, as we felt it may be needed for treatment versus prophylaxis. Based on our findings, lower doses of ketamine need to be investigated to determine the optimal dose of ketamine for the treatment of postoperative shivering.

In conclusion, 0.5 and 0.75 mg/kg IV ketamine provides a more rapid onset of effect than meperidine 25 mg for the treatment of postoperative shivering, but its side effect profile may limit its use.

Footnotes

Accepted for publication September 10, 2007.

REFERENCES

1. De Witte J, Sessler DI. Perioperative shivering: physiology and pharmacology. Anesthesiology 2002;96:467–84[Web of Science][Medline]
2. Wrench IJ, Cavill G, Ward JEH, Crossly AWA. Comparison between alfentanil, pethidine and placebo in the treatment of post-anaesthetic shivering. Br J Anaesth 1997;79:541–2[Abstract/Free Full Text]
3. Terasako K, Yamamoto M. Comparison between pentazocine, pethidine and placebo in the treatment of post-anaesthetic shivering. Acta Anaesthesiol Scand 2000;44:311–12[Web of Science][Medline]
4. Dal D, Kose A, Honca M, Aknci SB, Basgul E, Aypar U. Efficacy of prophylactic ketamine in preventing postoperative shivering. Br J Anaesth 2005;95:189–92[Abstract/Free Full Text]
5. Sagr O, Gulhas N, Toprak H, Yucel A, Begec Z, Ersoy O. Control of shivering during regional anaesthesia: prophylactic ketamine and granisetron. Acta Anaesthesiol Scand 2007;51:44–9[Web of Science][Medline]
6. Crossly AWA, Mahajan RP. The intensity of postoperative shivering is unrelated to axillary temperature. Anaesthesia 1994; 49:205–7[Web of Science][Medline]
7. Sharma DR, Thakur JR. Ketamine and shivering. Anaesthesia 1990;45:252–3[Web of Science][Medline]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kose, E. A. Articles by Aypar, U. Search for Related Content PubMed PubMed Citation Articles by Kose, E. A. Articles by Aypar, U. Related Collections Ambulatory Pharmacology