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Perioperative complications

Antishivering effects of two different doses of intrathecal meperidine in caesarean section: a prospective randomised blinded study

Khan, Zahid H; Zanjani, Amir P; Makarem, Jalil; Samadi, Shahram

Author Information
European Journal of Anaesthesiology: March 2011 - Volume 28 - Issue 3 - p 202-206
doi: 10.1097/EJA.0b013e3283430802



The incidence of shivering has been reported to be about 36–85% after spinal anaesthesia.1–3 In a recent meta-analysis, the average incidence of shivering was 52%.1

It may be associated with physical stressors such as increased oxygen consumption up to 600% and CO2 production,2 a rise in blood pressure (BP) and increased lactic acid production. These stressors are more serious in patients with anaemia, compromised cardiopulmonary system or valvular heart disease due to an increase in heart rate (HR) and BP. Shivering may also increase intraocular or intracranial pressure and wound pain; it may also interfere with electrocardiographic and pulseoxymetric monitoring.4 Shivering occurs in up to 85% of patients undergoing caesarean delivery under regional anaesthesia,4 which is the commonest method of anaesthesia used for caesarean section in developed countries.3 Neuraxial blockade reduces shivering for the duration of the accompanying sympathetic block. This same sympathetic block allows vasodilatation that allows uncontrolled heat loss from the lower half of the patient. Shivering starts as the block recedes and normal homoeostatic mechanisms return. The shivering ensues after the effect of local anaesthetics is over, reflecting a high incidence of shivering in these patients post-operatively. Thus, either treatment or prevention of shivering is a relevant medical intervention.

Several strategies have been advocated to prevent hypothermia and shivering during spinal anaesthesia, such as perioperative active warming or pharmacologic interventions such as clonidine, anti-HT3, MgSO4, meperidine, and so on.1

Although the prevention of shivering seems to be a useful goal, Kranke et al.1 in their meta-analysis demonstrated that to prevent shivering in one single patient, four patients need to receive prophylactic clonidine or meperidine. The antishivering effect of intravenous meperidine is attributed to its role in decreasing the shivering threshold due to its effect on the Kappa opioid receptor.5–7 Its action on α2b adrenoreceptor subtype is another evolving mechanism for its antishivering effect.8 Different dose regimens of meperidine have been employed via the intrathecal route to prevent shivering in patients,1,9–13 but there is a consensus regarding the best dose. This study compared the antishivering effects of two different doses of intrathecal meperidine (ITM) in patients undergoing caesarean section under spinal anaesthesia.


After ethics committee approval and informed consent from all patients, 98 patients assessed for eligibility and 72 patients were enrolled in the study as shown in Fig. 1. This prospective, randomised double-blinded study was performed from August 2006 to December 2007 in Imam Khomeini Medical Centre. Seventy two parturients [American Society of Anesthesiologists (ASA) physical status І or ІІ] who were scheduled for elective caesarean section under spinal anaesthesia were enrolled. The blinded anaesthesiologist allocated patients randomly into three groups by randomised block design. No patient was excluded after randomisation.

Fig. 1
Fig. 1

Patients with pre-operative fever (>38°C), diabetes, placenta praevia, preeclampsia, Parkinson's disease, hypo or hyperthyroidism, Raynaud's syndrome, obese patients (weight >100 kg), patients shorter than 152 cm, those with a history of allergy to the study medications, and patients receiving vasodilators were excluded from the study.

A power analysis was performed to determine a sufficient sample size in establishing a significant difference in the incidence of shivering based on the results of a preliminary study, using an α value of 0.05 and a power of 0.8. The incidence of shivering was 60% in group M0 and 17% in group M2 in our preliminary study. This determined that a sample size of 24 patients per group was adequate.

Spinal anaesthesia was performed with a 25-G Quincke needle (the needle available and commonly used in our centre) in the sitting position (mid-line approach). We tried L3–4 level if L4–5 failed. In group M0, bupivacaine 10 mg was injected without any meperidine. Two millilitres of 0.5% bupivacaine with 12.5 mg meperidine was injected in group M1, whereas the same dosage of bupivacaine with 25 mg meperidine was injected in group M2. In all the three groups, isotonic saline was added to achieve equal volumes for intrathecal administration. The prepared solutions were warmed to a temperature of 37°C and patients were covered with blankets but were not actively warmed.

All patients had two venous catheters inserted (one 20G and one 18G), and 10 ml kg−1 Ringer's solution warmed to 37°C was infused before spinal block. All patients were covered with one layer of surgical drapes over the chest, thighs and calves but not actively warmed. An anaesthesiologist who was blinded to the drug and the allocated group performed the spinal block. After injection, patients were immediately placed supine with a left lateral tilt and oxygen 5 l min−1 was administered via a Hudson mask.

Sensory block was evaluated by pinprick every 5 min during the first 30 min and then every 10 min. The level of sensory spinal block was evaluated during operation and in the post-anaesthesia care unit (PACU). A fixed and blinded trained anaesthesiology resident evaluated shivering intensity and graded it with a scale described by Crossley and Mahajan14 every 5 min during the intraoperative and post-operative period: 0, no shivering; 1, no visible muscle activity but piloerection, peripheral vasoconstriction, or both are present (other causes excluded); 2, muscular activity in only one muscle group; 3, moderate muscular activity in more than one muscle group, but no generalised shaking; and 4, violent muscular activity that involves the whole body. Patients were judged to have shivering when they displayed grade 3 or 4 activity for at least 3 min. Our monitoring consisted of non-invasive blood pressure with a brachial cuff, capnography with a catheter within the Hudson mask and continuous pulse oxymetry from the right upper limb. Tympanic probes measured core temperature, and skin thermometers in the axillary region measured skin temperature. We recorded HR, SBP and DBP, peripheral oxygen saturation, core and surface temperature as baseline values 10 min after settling the patient on the operating table, then after spinal block every 3 min till 30 min and then every 5 min. Core and skin temperatures were recorded every 20 min until the end of section and during the stay in PACU. The ambient temperature was maintained in range 21–23°C measured on a wall thermometer. A blinded observer recorded all the data, with a special emphasis on recording the highest and the lowest values.

Apgar scores were recorded at 1 and 5 min after birth by our blinded co-worker. Duration of surgery and weeks of pregnancy were recorded. Hypotension was defined as SBP less than 100 mmHg or 20% decrease in SBP. Hypotension was treated with 10 mg intravenous ephedrine and repeated if necessary. HR below 50 beats min−1 was treated with intravenous atropine 0.5 mg. If a patient had both nausea and hypotension, we administered intravenous ephedrine 10 mg. Nausea with normal BP or HR was treated with intravenous metoclopramide 10 mg.

Patients were allowed to leave PACU when their sensory level was below T10 or four dermatomes' regression from the peak. We considered the time from injecting ITM until the patient left PACU as ‘time to recovery’.

Quantitative variables such as age, weight, height, BMI, basic and intraoperative haemodynamic parameters (HR, BP), O2 saturation, peripheral and core temperature, Apgar score, gestational age were compared between groups by one way analysis of variance (ANOVA). For ordinal qualitative variables such as the highest segment blocked and shivering intensity, scores were compared between three groups by Kruskal–Wallis H-test and Mann–Whitney U-test was used for between two-group comparisons by Bonferroni correction if needed. Dichotomous nominal variables such as nausea, vomiting, tachycardia and bradycardia, hypotension, desaturation, administration of ephedrine, atropine or metoclopramide were compared by either χ2 test or Fisher's exact test as appropriate. SPSS software version 16 was applied for statistical analysis and a P value less than 0.05 was assumed to be significant.


Data from all the patients were analysed. There were no missing data or loss to follow-up. Demographic data, duration of surgery and basic haemodynamic parameters (HR, SBP and DBP) were comparable between the three groups (Table 1, P > 0.05).

Table 1
Table 1:
Patient characteristics in three groups

Significant attenuation of shivering was seen in patients having received meperidine, and the findings obtained were statistically significant (Fig. 2, P = 0.03). Group comparisons showed shivering to be more intense in the M0 group than M1 and M2 groups with P values equal to 0.003 and less than 0.001, respectively. However, there was no statistical difference between the intensity of shivering in groups M1 and M2 (P = 0.22). Clinically significant shivering was present in group M0 (4/24, 16.7%) and absent in groups M1 and M2 (P = 0.03). No patient displayed grade 4 shivering.

Fig. 2
Fig. 2

Time to recovery was found to be 102 ± 18, 103 ± 11 and 109 ± 18 min in groups M0, M1 and M2, respectively (P = 0.34).

Significant adverse effects were compared between the groups (Table 2). Pruritus and respiratory depression were not seen in any of the groups.

Table 2
Table 2:
Adverse effects in the three groups

Apgar scores were similar for the three groups (P > 0.05).

No patient had to be excluded due to inadequate spinal anaesthesia or the need for supplementary sedation.


Physiological shivering is triggered by hypothermia. However, it may also occur in normothermic patients,2 suggesting that in these cases, some other mechanisms such as uninhibited spinal reflexes, post-operative pain, decreased sympathetic activity, pyrogen release, adrenal suppression and respiratory alkalosis may contribute to its occurrence.15 General anaesthesia and neuraxial block alter the function of the autonomic nervous system, impairing its role in thermoregulation. Several studies indicate that regional anaesthesia significantly impairs thermoregulation and predisposes the patient to hypothermia.15 Neuraxial anaesthesia probably impairs thermoregulation mostly by producing peripheral vasodilatation as a result of the associated sympathetic blockade. This causes increased heat loss through the skin, resulting in a flow of heat from the core to the periphery. Moreover, it also alters central nervous system responses by decreasing vasoconstriction and increasing sweating thresholds.15

Wrench et al.16 described 0.35 mg kg−1 as the minimum effective intravenous dose of meperidine to treat shivering. ITM has been used in larger doses (0.5–1.8 mg kg−1) as a sole anaesthetic. These doses were associated with unacceptable incidences of nausea and vomiting.17–19 Our literature search failed to find studies comparing different doses of ITM for its antishivering effects. In this study, both 12.5 and 25 mg ITM caused significant reduction in shivering in comparison with the non-meperidine group; however, significant shivering was not a big problem in the non-meperidine group as it occurred only in four of the patients. There tended to be a greater reduction in shivering intensity with higher doses, that is, 25 mg ITM as shown in Fig. 2, but the increase in nausea and vomiting rates was too great to recommend the use of a higher dose; furthermore, nausea and vomiting were also noticeable with lower doses of intrathecal meperidine as well.

Roy et al.12 are of the opinion that increasing the dose of meperidine is not associated with an increased incidence of side-effects, although others state that the side-effects of meperidine are dose related.20 Booth et al.21 showed that 25 mg ITM prolonged analgesia and decreased the need for morphine compared to 15 mg ITM during labour, but was associated with a higher incidence and severity of nausea and vomiting.

In this study, we did not actively warm the patients, but the fluids infused were warmed. The role of warming fluids in reducing hypothermia has been referred to in other studies22 as well; however, in our study, we failed to prevent patients from becoming hypothermic (Table 1). As reported previously,22 forced air warming can serve as a valuable strategy in averting hypothermia and as a result curtail or altogether prevent shivering. As our aim was not to compare forced air warming with intrathecal meperidine, we cannot claim the superiority of one over the other, but the idea seems tempting and could be pursued in future studies.

The high frequency of nausea and vomiting following ITM makes it hard to justify its use for the prevention of post-operative shivering, particularly when simpler, proven methods (such as forced air warming) are available and produce fewer side-effects.1

In conclusion, the use of intrathecal meperidine in the doses used in this study is an effort to prevent shivering. However, the fact that the lowest dose that we used (12.5 mg) completely prevented clinically significant shivering suggests that it might be worth considering lower doses of meperidine (perhaps with fewer side-effects) for this purpose. As the incidence of nausea and vomiting is significantly more than that of shivering, it appears rather illogical to use high doses of intrathecal meperidine in an effort to prevent shivering.


This study was performed by the authors and without financial assistance from outside the department. There are no conflicts of interest.


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caesarean section; meperidine; shivering; spinal anaesthesia; spinal injections

© 2011 European Society of Anaesthesiology