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Anesth Analg 2004;98:230-234
© 2004 International Anesthesia Research Society

OBSTETRIC ANESTHESIA

Intrathecal Meperidine Decreases Shivering During Cesarean Delivery Under Spinal Anesthesia

Jean-Denis Roy, MD, Michel Girard, MD, MHPE, FRCP(C), and Pierre Drolet, MD, FRCP(C)

Département d’Anesthésiologie, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Canada

Address correspondence to Michel Girard, MD, MHPE, FRCP(C), Hôpital Maisonneuve-Rosemont, Département d’Anesthésiologie, 5415 Boul l’Assomption, Montréal, QC, Canada, H1T 2M4. Address e-mail to michel.girard.2{at}umontreal.ca Reprints will not be available from the authors.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Shivering associated with spinal anesthesia is uncomfortable and may interfere with monitoring. We performed this prospective, double-blinded, and randomized study to determine whether intrathecal meperidine (0.2 mg/kg) decreases the incidence and intensity of shivering after spinal anesthesia for cesarean delivery. Forty parturients scheduled for nonemergent cesarean delivery were enrolled in two groups. Spinal anesthesia consisted of hyperbaric bupivacaine (0.75%; 10.5 mg), morphine 0.15 mg, and, in the experimental group, meperidine (0.2 mg/kg) or, in the control group, normal saline. Data collection, including sensory block level, blood pressure, core temperature, and shivering intensity, was performed every minute for 10 min, every 3 min for 33 min, and then every 5 min until the sensory level receded to L4. Time to highest sensory level, maximum number of blocked segments, sensory and motor blockade regression, and systolic blood pressure showed no difference between groups. The incidence of shivering was less (P < 0.02) in the meperidine group, as was its intensity (P < 0.003). Intrathecal meperidine (0.2 mg/kg) is effective in reducing the incidence and intensity of shivering associated with spinal anesthesia for cesarean delivery.

IMPLICATIONS: Previous studies have suggested that IV meperidine is helpful for treating intraoperative shivering. This study was undertaken to evaluate spinal meperidine and found that it decreases the incidence and intensity of shivering associated with spinal anesthesia for cesarean delivery.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Shivering associated with spinal and epidural anesthesia is common, occurring in up to 56.7% of patients (1). Shivering is uncomfortable for the patient and may interfere with monitoring of electrocardiogram, blood pressure (BP), and oxygen saturation. It increases oxygen consumption, lactic acidosis and carbon dioxide production (2–4). Those effects are particularly bothersome in the obstetrical population. Although IV meperidine is widely used to treat shivering after spinal anesthesia (5), little is known about its pharmacologic prevention. Chen et al. (1) have suggested that a small dose of intrathecal meperidine might decrease the incidence of shivering and the discomfort associated with it in a nonobstetrical population. Because anesthesiologists rely heavily on regional anesthesia in obstetrics and considering the frequent incidence of shivering associated with neuraxial blockade in the obstetrical population, it seems logical to evaluate whether its incidence and intensity can be reduced by the addition of meperidine to the spinal mixture, with minimal effect on the characteristics of the block.

This prospective, double-blinded, and randomized study was performed to determine whether meperidine (0.2 mg/kg), added to a bupivacaine and morphine spinal mixture, decreases the incidence and intensity of shivering during spinal anesthesia for cesarean delivery. The effects of added meperidine on the characteristics of the spinal block were also studied.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
After ethics committee approval and written, informed consent, 40 parturients (ASA physical status I or II) scheduled for nonemergent cesarean delivery under spinal anesthesia were enrolled. Parturients with contraindications to regional anesthesia, allergy to the study medication, a height <152 cm, or severe preeclampsia were excluded.

Patients were randomly divided into two groups by random drawing of sealed envelopes. Medication was prepared by an anesthesiologist not involved in the study. All therapeutic interventions were standardized. Before the spinal anesthesia was performed, patients were placed under standard monitoring and received IV lactated Ringer’s solution 15 mL/kg. During anesthesia, oxygen was given, and patients were covered with drapes but not actively warmed. All fluids were warmed to 37°C. Spinal anesthesia consisted of hyperbaric bupivacaine (0.75%; 10.5 mg), morphine 0.15 mg, and, in the experimental group, meperidine (0.2 mg/kg) or, in the control group, an equivalent volume of normal saline. Spinal anesthesia was performed in the sitting position at the L3-4 interspace with a midline approach by using a 27-gauge Whitacre needle. After spinal injection, parturients were placed supine with left uterine displacement.

The time at the end of the injection was defined as T0. Sensory anesthesia was evaluated by pinprick at 1-min intervals for 10 min, 3-min intervals for 33 min, and then 5-min intervals until regression to L4. Once patients were in the postanesthesia care unit, motor blockade was assessed with the Bromage scale (6): 1, unable to move feet; 2, able to move feet only; 3, just able to move knees; and 4, full flexion of knees and feet. The BP was measured simultaneously with sensory levels and shivering intensity. Hypotension was defined as a decrease in systolic BP to <90 mm Hg or 20% less than baseline value. It was treated with 5–10 mg of ephedrine IV. Pruritus was treated with diphenhydramine 25 mg IV, and metoclopramide 10 mg IV was administered for nausea. Supplemental intraoperative analgesia was limited to IV fentanyl (25–50 µg), which was standardized and used as a rescue dose if necessary. The tympanic temperature was monitored every 20 min (Thermoscan Pro-LT Model IR-2; Thermoscan Inc., San Diego, CA). The operating room temperature was maintained at 21°C–23°C. Shivering was graded with a scale described by Crossley and Mahajan (7): 0, no shivering; 1, piloerection or peripheral vasoconstriction but no visible shivering; 2, muscular activity in only one muscle group; 3, muscular activity in more than one muscle group but not generalized shivering; and 4, shivering involving the whole body. Pruritus, nausea, and vomiting were noted as they occurred. Apgar scores were recorded at 1, 5, and 10 min. Duration of the surgery and weeks of pregnancy were recorded. A blinded observer collected all data.

Demographic data, time to highest sensory level, fentanyl doses, incidence of shivering, nausea, and ephedrine administration were compared by using Student’s t-test or Fisher’s exact test. The regression of the sensory and motor blocks was compared with survival curves followed by a log-rank test. The BP and temperature data were compared by using analysis of variance for repeated measures. The maximal intensity of shivering recorded for each patient was studied with both the Mann-Whitney U-test and the {chi}2 test for trends. The highest shivering intensity score recorded for each parturient was used for calculation. Our clinical experience led us to an incidence of close to 90% (an incidence of 85% in our study). To find a 50% reduction of this incidence, with an {alpha} error of 0.05 and a ß error of 0.2, a sample size of 20 patients per group was necessary. A P < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
There was no difference between groups with regard to demographic data, duration of surgery, or Apgar scores. Time to highest sensory level and maximum number of segments blocked showed no difference between the groups (Table 1). Regression of sensory (Fig. 1A) and motor (Fig. 1B) blocks was similar between the groups. The doses of fentanyl, diphenhydramine, or metoclopramide administered showed no difference. The systolic BP was similar between groups for each time interval, as was patient temperature. The incidence of shivering (Fig. 2) was less in the meperidine group (9 of 20 versus 17 of 20; P < 0.02), as was its maximum intensity for each patient (P < 0.003) (Fig. 3).


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  		Table 1. Demographic and Surgical Data (Not Significant)
 


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  		Figure 1. Sensory (A) and motor (B) block regression (not significant). Group S = control group; Group M = experimental group.

 


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  		Figure 2. Incidence of shivering; *P < 0.02. Group S = control group; Group M = experimental group.

 


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  		Figure 3. Maximum shivering intensity for each patient: 0, no shivering; 1, piloerection or peripheral vasoconstriction but no visible shivering; 2, muscular activity in only one muscle group; 3, muscular activity in more than one muscle group but not generalized shivering; 4, shivering involving the whole body (7) (P < 0.003 with both the Mann-Whitney U-test and the {chi}2 test for trends). Group S = control group; Group M = experimental group.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
These data show that adding a small dose of meperidine to the intrathecal mixture during anesthesia for cesarean delivery reduces the incidence and severity of shivering without affecting the characteristics of the block. IV drugs are the "gold standard" for the treatment of postoperative shivering. Although IV meperidine has long been used for the treatment of postanesthetic shivering (8), it is generally administered to treat shivering that has already begun. IV meperidine is particularly effective in treating shivering after anesthesia. In a recent metaanalysis, Kranke et al. (9) showed that when cessation of shivering was evaluated five minutes after the administration of meperidine 25 mg IV, only 1.3 patients had to be treated to stop shivering in 1 patient (number needed to treat, 1.3; relative risk, 9.6; 95% confidence interval, 5.7–16) (9). As compared with treatment, prevention of shivering has not been well investigated. When IM meperidine (25 mg) was evaluated during spinal anesthesia, it was associated with less frequent (10%) shivering compared with a placebo group (56.7%; P < 0.005) (10). The only description for the effect of intrathecal meperidine to prevent shivering can be found in the non-English literature (1). The authors in that report, in a nonobstetrical population, found a reduced incidence of shivering with intrathecal meperidine (0.2 mg/kg) versus placebo (16.7% versus 56.7%) added to tetracaine (12–16 mg) (P < 0.005). Although the IV treatment of shivering is effective, prevention of shivering has two advantages: First, it is a preventive treatment; therefore, patients are spared the negative experience associated with shivering. Second, the administration of meperidine 25 mg IV (9) to a pain-free woman after a cesarean delivery could be associated with unwanted side effects, such as those discussed below.

Meperidine has been used as the sole drug for spinal anesthesia in doses ranging from 0.5 to 1.8 mg/kg (11,12). When it is used as the sole drug, reported side effects include nausea, vomiting, pruritus, drowsiness, hypotension, bronchospasm, bradycardia, and respiratory depression (11–14). Side effects are reported to be dose related (15). Transient neurological symptoms were reported once after the intrathecal administration of 50 mg of meperidine to a 70-year-old patient for a bladder operation performed in the lithotomy position (16), and it may be that transient neurological symptoms are dose related, as in the case of lidocaine (17). The 0.2 mg/kg dose used in this study was small when compared with doses used when meperidine was the primary intrathecal drug. Although the dose used in this study was the same as in the only other study previously reported on this subject (1), it is possible that it is not the optimal one. In view of the small incidence of side effects in this work, a larger dose might be more effective.

It is possible that the antishivering effect of spinal meperidine could be caused by its systemic absorption. However, IV meperidine has been administered to plasma levels of 0.6 and 1.8 µg/mL to study its antishivering effect (18). Meperidine plasma concentrations of 400 to 700 ng/mL are associated with postoperative analgesia (15). Conversely, meperidine plasma levels of 107 ± 20 ng/mL have been reported after intrathecal injection of 1 mg/kg (15), a dose five times larger than the one used in this study. It thus appears unlikely that the antishivering effect observed in this study was caused by the systemic absorption of the intrathecally-administered meperidine.

Meperidine is a combined µ- and {kappa}-receptor agonist. IV meperidine is much more effective in treating shivering than equianalgesic doses of other µ-opioid agonists, such as fentanyl, alfentanil, sufentanil, or morphine (8,19,20). The efficacy of meperidine for shivering is largely preserved during the administration of a standard dose of naloxone (0.5 µg · kg-1 · min-1) but is virtually obliterated by a 10-fold increase in the dose (5.0 µg · kg-1 · min-1) (8,21). These data suggest that the action of meperidine on shivering is, in part, mediated by non-µ-opioid receptors. The most likely receptor involved is the {kappa}-receptor, and meperidine possesses considerable {kappa}-activity. Thus, several authors now suggest that the antishivering effects of meperidine are mediated by {kappa}-receptor agonist activity (8,21,22). A complete discussion of meperidine antishivering action mechanisms can be found in the recent literature (23).

The exact mechanism of shivering under spinal anesthesia has not been fully established. Hypotheses have been formed to explain the phenomenon (24–26). First, as with general anesthesia, heat is internally redistributed from the core to the peripheral compartment. Second, the loss of thermoregulatory vasoconstriction below the level of the blockade results in increased heat loss from body surfaces in excess of metabolic heat production. Third, there is altered thermoregulation characterized by a small (approximately 0.5°C) decrease in vasoconstriction and a slight increase in the sweating threshold.

In this study, side effects related to meperidine, such as nausea, vomiting, and pruritus, were not noted. Diphenhydramine was available for treatment of pruritus because it is still used for this symptom at our institution; the suitability of this treatment in this patient population, however, is questionable (27). The respiratory-depressant action of opioids represents their single serious adverse effect and has been reported with much larger doses (50 mg) of intrathecal meperidine (28). Clinically significant respiratory depression did not occur in any of our patients. Many questions still remain unanswered, including the optimal dose of intrathecal meperidine to prevent shivering. Larger studies will be needed to evaluate optimal dosing.

In conclusion, shivering continues to be a common problem after spinal anesthesia for cesarean delivery. Although the mechanisms underlying the ability of meperidine to decrease the incidence of shivering are unclear, its intrathecal use (0.2 mg/kg) reduces the incidence and intensity of shivering associated with intrathecal anesthesia for cesarean delivery. Adding meperidine (0.2 mg/kg) does not modify the efficacy of the sensory and motor block or its maximum spread. Furthermore, it appears that this dose of meperidine is not associated with an increased incidence of side effects.


   Acknowledgments
 
The authors wish to thank Mrs. Christiane Côté, BSc, for her assistance in the data collection.


   Footnotes
 
Presented in part at the annual meeting of the Canadian Anesthesiologists’ Society, Halifax, Canada, June, 2001.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

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Accepted for publication August 13, 2003.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2004 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press