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Received: 9.6.2005 Accepted: 27.4.2006

Journal of Research in Medical Sciences May & June 2006; Vol 11, No 3. 151

Original Article

Tramadol versus meperidine in the treatment of shivering during

spinal anesthesia in cesarean section

R. Talakoub*, Sh. Noori Meshkati**

Abstract

BACKGROUND: The aim of this study was to evaluate the efficacy and side effects of tramadol comparing withmeperidine on post-spinal shivering in cesarean section.

METHODS: In a prospective, controlled, randomized, double-blind clinical trial 73 ASA-I pregnant patients candidatesof cesarean section under spinal anesthesia who had shivering postoperatively were selected and classified into twogroups receiving tramadol or meperidine to control postoperative shivering. Spinal anesthesia was done by injection of

epinephrinized 5% lidocaine at L3-L4or L4-L5segment. Pruritis, somnolence, dizziness, nausea, vomiting and the dura-tion of shivering control were evaluated and recorded. All data were analyzed by using Fisher and Chi-square tests.

RESULTS:There were no significant differences between two groups in age (P = 0.1) and weight (P = 0.8) of patients.There was no significant difference in response rate after injection of both drugs (P = 0.3). The time elapsed from

treatment to ceased shivering was significantly less (P = 0.001) but frequency of somnolence (P = 0.001), nausea (P =0.001) and vomiting (P = 0.005) were significantly more in tramadol group. Dizziness was significantly more commonin meperidine group (P = 0.001) and pruritis was not seen in any group.

CONCLUSION:Tramadol is more effective in controlling post-spinal shivering but results in more frequent nausea, vom-iting and somnolence in comparison with meperidine.

KEYWORDS:Shivering, meperidine, tramadol, spinal anesthesia, cesarean section.

JRMS 2006; 11(3): 151-155

egional anesthesia (extraxdural/sub-arachnoid) is a safe and popular anes-thetic technique for cesarean section,

both in elective and emergency situations. Oneof the common complications of this techniqueis shivering. The origin of postoperative shivering is un-clear and various mechanisms have been pro-posed. Shivering may happen as a thermo-

regulatory response to hypothermia or musclehyperactivity with clonic or tonic patterns, anddifferent frequencies have been reported 1.However, in the postoperative period, muscleactivity may be increased even with nor-mothermia suggesting that other mechanismsthan heat loss and subsequent decrease in core

temperature may contribute to the develop-ment of shivering 2. These include inhibitedspinal reflexes, postoperative pain, decreasedsympathetic activity, pyrogen release, adrenalsuppression and respiratory alkalosis 1. Shivering causes distress to the patient. Itmay also increase metabolic rate by up to400%, induce arterial hypoxemia and lacticacidosis, increase intracranial pressure and it

may contribute to increased wound pain 3. Numerous pharmacological interventionshave been proposed for the treatment of post-operative shivering. Some researches suggestthat apart from applying radiant heat to thebody surface, shivering may be treated withmeperidine, clonidine or ketanserin 1. The

*Assistant professor of Anesthesiology, Isfahan University of Medical Sciences, Isfahan, Iran.**Anesthesiologist

Correspondence to: Dr Reihanak Talakoub, Assistant Professor of Anesthesiology, Isfahan University of Medical Sciences, Al-ZahraHospital, Isfahan, Iran. e-mail: [email protected]

R

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Treatment of shivering, tramadol versus meperidine Talakoub et al

152 Journal of Research in Medical Sciences May & June 2006; Vol 11, No 3.

relative efficacy of these different medicationshowever, remains unclear. Tramadol has beenused as an analgesic for labour pain withoutadversely affecting the mother or newborn 4. In

addition, it has been shown to be effective inthe treatment of postoperative shivering 5.Tramadol and meperidine are approximatelyequipotent with respect to analgesia 6. How-ever, the antishivering and analgesic effects ofthese two agents may be mediated via differ-ent receptors.

This prospective, double-blind and random-ized clinical study was performed to comparethe antishivering effects and the accompanyingside effects between tramadol and meperidinefor the treatment of post-spinal shivering inparturients.

MethodsAfter approval of the ethics committee and ob-taining patients written informed consent, 73ASA-I parturients who subsequently devel-oped shivering intra or postoperatively duringelective or emergency cesarean section underspinal anesthesia were studied. Patients with

known hypersensitivity to tramadol, thosewith a known history of alcohol or substanceabuse, or who received intramuscularmeperidine for labour pain within one hourwere excluded. Spinal anesthesia was insti-tuted at either L3-L4 or L4-L5 interspace by in-jection of 1.5 mg 5% epinephrinized lidocaine.The volume of preloading intravenous fluid,the use of ephedrine for hypotension, and thedose of local anesthetic were determined bythe attending anesthesiologists and were not

affected by enrollment in the study.All preloading fluids and drugs were givenat room temperature and the operating roomtemperature was kept at 21-23oC. Standardmonitoring of non-invasive blood pressure,ECG and pulse oximeter were used and bodytemperature was monitored via tympanicmembrane. Patients eligible for study wererandomized into two groups. Group T(tramadol) received 0.5 mg/kg tramadol andgroup M (meperidine) received 0.5 mg/kg

meperidine. Both drugs were given as slowly

as intravenous injection. Anesthesiologists andpatients were blind to the treatment. Randomi-zation and blindness of the study were assuredby a strict protocol.

Shivering was graded with a scale similar tothat validated by Crossley and Mahajan 7; 0 =no shivering, 1 = piloerection or peripheralvasoconstriction but no visible shivering, 2 =muscular activity in only one muscle group, 3= muscular activity in more than one musclegroup but no generalized shivering, 4 = thewhole body shivering. Only parturients whodeveloped grade 3 or 4 shivering for at least 3min were included. Before starting the opera-tion, two syringes contained 10 mg/ml of ei-ther tramadol or meperidine in 5 ml solutionwere prepared. Should the parturients developshivering and require treatment, an anestheticassistant not involved in any other way in thestudy would pick randomly from the set ofsealed envelops and pick out one of the twolabeled syringes as instructed in the envelop.The label on the syringe was removed beforepassing to the anesthesiologist and kept by theassistant until the end of the operation. The

administration of pre or intra-operativeopioids was not permitted. Patients were sup-plemented with oxygen 6 L/min by face maskand covered with sheets but not activelywarmed during anesthesia. The anti-shiveringeffect was assessed both by the parturients andby the observing anesthesiologist. The parturi-ents were asked to evaluate five minutes afterinjection the effect of the treatment as either noimprovement, slight improvement, or markedimprovement. The attending anesthesiologist

independently recorded the time that he or shesubjectively assessed the shivering to havesubsided and the response rate (shiveringceased after treatment in 15 min). If shiveringdid not subside after 15 min, the treatment wasconsidered not effective. Recurrence of shiver-ing, if any, was also recorded until the parturi-ent left the operating theatre suite. Side effectssuch as pruritis, somnolence, dizziness, nauseaand vomiting, also blood pressure, pulse andSpO2 were recorded before and every five

minutes till 15 min after spinal anesthesia as

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well as 5 min after treatment. The parturientstympanic temperature before starting opera-tion, in the beginning of shivering and at thecessation of shivering was measured. If partu-

rient developed nausea and vomiting after in-jection of the drugs, metoclopramide 10 mg IVwas administered. Data were analyzed withSPSS program, using Chi-square and Fishertest. A P-value 0.05

Values are number or mean SD.

Table 2.Post-spinal shivering responses and therapeutic complications.

Variable Tramadol Meperidine P value

Response rate 35 (97.2%) 34 (91.9%) 0.3

Time elapsed from treatmen 2.54 0.78 5.03 1.07 0.001to ceased shivering (min)

Nausea 28 (77.8%) 0(0) 0.001Vomiting 7 (19.4%) 0(0) 0.005Somnolence 20 (55.6%) 0(0) 0.001

Dizziness 0 (0) 10 (27%) 0.001

Values are n (%) or mean ( SD)

DiscussionThe results of this study indicate that bothtramadol (0.5 mg/kg) and meperidine (0.5mg/kg) effectively treated post-spinal shiver-ing. The mechanism of shivering under generalanesthesia is not fully understood. Possible

contributing factors are a decrease in core tem-

perature and misinformation from receptors. Adecrease in core temperature may be due to 1)sympathetic block which results in peripheralvasodilatation, increased cutaneous bloodflow, and subsequent increased heat lost viaskin, 2) a cold operating room and/or the

rapid infusion of crystalloid solutions at room

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154 Journal of Research in Medical Sciences May & June 2006; Vol 11, No 3.

temperature or 3) the direct effects of cold an-esthetic solutions upon thermo-sensitive recep-tors within the spinal cord.

Treatment modalities have included cover-

ing the patient with blankets, application ofradiant heat and warming the operating roomsuits 8-12. The use of warm local anesthetic solu-tions or warm intravenous fluid has met withvarying degrees of success 11,13. Our study wasdesigned to standardize these possible con-founding factors while reflecting the usualpractice in our institution. Operating roomtemperature was held constant at 21 - 23oC, in-travenous fluids and drugs were administeredat room temperature. Tympanic temperaturewas also recorded in the beginning of the op-eration. Tramadol is an analgesic with agonist prop-erties on opioid receptors. It also activates themonoaminergic receptors of the descendingspinal inhibitory pathway of pain. The mainopioid effect of tramadol is mediated via the -receptor, with minimal effect at kappa or

sigma binding sites. Tramadol also inhibits invitro synaptosomal noradrenaline and sero-

tonin uptake, which contributes to its analgesiceffects 6. Our study demonstrated thattramadol, in a dose of 0.5 mg/kg controlledshivering in parturients undergoing cesareansection under regional anesthesia. It is alsoshown that the incidence of nausea, vomitingand somnolence at this dose were more intramadol group which is different with thefinding of Yu-chuan Tsai in this respect 14. Based on our study it was not possible todraw conclusions about the mechanisms in-

volved in the anti-shivering effect of tramadol.For meperidine, the effect is most likely medi-ated via receptors other than the -receptor,

in particular the K-receptor. This is supportedby observations that meperidine controlled

shivering better than morphine and fentanyl,and that the anti-shivering effect of meperidinewas not reversed by low dose, but by highdose naloxone 15,16.

Tramadol has minimal K-receptor activity 6.The -receptor activity of tramadol was also

unlikely to be important in the effect we ob-served. Pure -agonists such as morphine and fen-

tanyl do not have significant anti-shivering ef-fects 15. Thus, it is highly probable that the anti-shivering effect of tramadol was mediated viaits serotonergic or noradrenergic activity orboth.

Our study did not control tightly the vari-ous factors which might influence the inci-dence of shivering, such as the temperature ofdrugs and intravenous fluids. However, thisshould not have affected the validity of ourcomparisons. First, the current study focusedon the response after treatment, rather than theincidence of shivering. Second, by randomiza-tion, both groups had been subjected to a simi-lar degree of influence of these factors.

In this study, we have performed a com-

parison between tramadol and meperidine.However, tramadol does have advantages overmeperidine in that it is not a controlled drugand it causes less respiratory depression anddizziness than other opioids at equivalent dos-ages 17,18. In conclusion, both tramadol (0.5 mg/kg)and meperidine (0.5 mg/kg) effectively treatedpatients with post-spinal shivering, but themore frequent incidence of side effects oftramadol such as nausea, vomiting and somno-

lence may attenuated its use as an anti-shivering drug. Because of these side effects oftramadol, further study is required to find theminimum effective dose of tramadol to ceaseshivering.

References1. Miller R. Anesthesia.4 ed. Philadelphia: Lippincott Williams & Wilkins, 1994.2. Horn EP, Sessler DI, Standl T, Schroeder F, Bartz HJ, Beyer JC et al. Non-thermoregulatory shivering in patients

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7. Crossley AW, Mahajan RP. The intensity of postoperative shivering is unrelated to axillary temperature.An-aesthesia1994; 49(3):205-207.

8. Chamberlain DP, Chamberlain BD. Changes in the skin temperature of the trunk and their relationship to

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10. Waters HR, Rosen N, Perkins DH. Extradural blockade with bupivacaine. A double blind trial of bupivacainewith adrenaline 1-200,000, and bupivacaine plain.Anaesthesia1970; 25(2):184-190.

11. Walmsley AJ, Giesecke AH, Lipton JM. Contribution of extradural temperature to shivering during ex-

tradural anaesthesia.Br J Anaesth1986; 58(10):1130-1134.12. Sharkey A, Lipton JM, Murphy MT, Giesecke AH. Inhibition of postanesthetic shivering with radiant heat.An-esthesiology1987; 66(2):249-252.

13. Webb PJ, James FM, III, Wheeler AS. Shivering during epidural analgesia in women in labor. Anesthesiology1981; 55(6):706-707.

14. Tsai YC, Chu KS. A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shiv-ering in parturients.Anesth Analg2001; 93(5):1288-1292.

15. Pauca AL, Savage RT, Simpson S, Roy RC. Effect of pethidine, fentanyl and morphine on post-operative shiv-ering in man.Acta Anaesthesiol Scand1984; 28(2):138-143.

16. Kurz M, Belani KG, Sessler DI, Kurz A, Larson MD, Schroeder M et al. Naloxone, meperidine, and shivering.Anesthesiology1993; 79(6):1193-1201.

17. Houmes RJ, Voets MA, Verkaaik A, Erdmann W, Lachmann B. Efficacy and safety of tramadol versus morphinefor moderate and severe postoperative pain with special regard to respiratory depression .Anesth Analg1992;

74(4):510-514.18. Vickers MD, Paravicini D. Comparison of tramadol with morphine for post-operative pain following abdomi-nal surgery.Eur J Anaesthesiol1995; 12(3):265-271.

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