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Home , Dexmedetomidine, Postanesthetic shivering

Ellakany, Int J Anesthetic Anesthesiol 2014, 1:004 DOI: 10.23937/2377-4630/1004 International Journal of Volume 1 | Issue 2 Anesthetics and ISSN: 2377-4630 Research Article: Open Access Intrathecal Dexmedetomidine or Meperidine for Post-spinal Shivering Mohamed Hamdy Ellakany1*, Sherif A.Abdelhamed1 and Medhat M.MessehaGirgis2 1Anesthesia, intensive care and , Medical research institute, Alexandria university, Egypt 2Anesthesia and surgical intensive care, Faculty of Medicine, Mansoura university, Egypt *Corresponding author: Mohamed Hamdy Ellakany, Lecturer of , Anesthesia, intensive care and pain management, Medical research institute, Alexandria university Postal address:165 Elhorreya Avenue-Alhadara- Alexandria, Egypt, Tel: 01223525264, E-mail: [email protected]

and systemic release of pyrogens [1]. Spinal anesthesia impairs the Abstract thermoregulation system, it inhibits the tonic vasoconstriction, Background: Shivering occurs frequently during the perioperative which plays a significant role in temperature regulation [2]. Spinal period. A prospective, randomized, double-blind study was done anesthesia also causes redistribution of core heat from the trunk to compare between intrathecal dexmedetomidine (5mcg) and intrathecal meperidine (0.2mg/kg) for decreasing the incidence and (below the block level) to the peripheral tissues. These two effects intensity of shivering after spinal anesthesia for lower abdominal predispose patients to hypothermia and shivering [3]. Shivering operations. increases oxygen consumption, carbon dioxide production, lactic acidosis and metabolic rate by up to 400% [4,5]. Dexmedetomidine Methods: Seventy five patients scheduled for lower abdominal operations under spinal anesthesia were randomly allocated to is a highly selective alpha-2-adrenoceptor with potent effects three groups. Spinal anesthesia consisted of 12.5 mg hyperbaric on the central nervous system and it was used for prevention and bupivacaine 0.5% in addition to dexmedetomidine (5mcg) (group treatment of shivering associated with general or spinal anesthesia [6- D) or meperidine (0.2 mg/kg) (group M) or, normal saline (group 8]. Many other drugs have been used to treat perianesthetic shivering, S). Different parameters, including sublingual temperature, sensory including meperidine, , , and doxapram; and block, motor block, incidence and intensity of shivering, blood most studies have concluded that meperidine is considerably more pressure, heart rate, pruritus, nausea, and vomiting was performed effective in treating shivering than others [9-11]. Adding a small dose at 10 minute intervals. Statistical analysis was carried out using of meperidine to the intrathecal mixture during spinal anesthesia statistical package for social sciences (SPSS) version 15.0 for windows and employing ANOVA and chi-square test with post-hoc reduces the incidence and severity of shivering. and is known to comparisons with Bonferroni’s correction. retain characteristics of the sensory block [12-14]. The aim of this study was to compare between intrathecal dexmedetomidine and Results: Hypothermia was recorded in 17 patients (68%) in group intrathecal meperidine on the incidence and severity of shivering D, 16 patients (64%) in group M and 18 patients (72%) in group S, following spinal anesthesia. while shivering developed in 5 patients (20%) in group D, 6 patients (24%) in group M and 23 patients (92%) in group S, however, Material and Methods pruritus, nausea and vomiting was more common in the meperidine group compared to the other two groups. After approval of the local ethical committee, seventy five Conclusion: Intrathecal dexmedetomidine and meperidine patients (American Society of Anesthesiologists physical status I or lowered the incidence of shivering and increased duration of II, aged 20-50 years) scheduled for elective minor lower abdominal sensory and motor block during lower abdominal operations. operations under spinal anesthesia, were enrolled in the study. Intrathecal meperidine caused more pruritus, nausea and vomiting Exclusion criteria include patients with thyroid disease, Parkinson’s than intrathecal dexmedetomidine. disease, dysautonomia, Raynaud’s syndrome, cardiopulmonary Keywords disease, a history of allergy to the agents to be used, a need for blood Anesthesia, Dexmedetomidine, Meperidine, Shivering, Spinal transfusion during surgery, an initial core temperature above 37.5˚C or below 36.5˚C, use of vasodilators, or having contraindications to spinal anesthesia. All patients gave written informed consent to Introduction participate in this study. The temperature of the operating room was maintained at 21˚C to 22 ˚C (measured by a wall thermometer). Shivering is a protective mechanism by which heat production Intravenous fluids were administered at room temperature and given occurs, by vigorous involuntary muscle activity, to compensate for without warming. One layer of surgical drapes over the chest, thighs, the decreased core temperature in a normal healthy living body. The and calves were placed during the operation and then one cotton main mechanisms of shivering in patients undergoing surgery are blanket over the entire body postoperatively. No other warming mainly intraoperative heat loss, increased sympathetic tone, pain, device was used. A core temperature below 36˚C was considered

Citation: Ellakany MH, Abdelhamid SA, MessehaGirgis MM (2014) Intrathecal Dexmedetomidine or Meperidine for Post-spinal Shivering. Int J Anesthetic Anesthesiol 1:004. doi.org/10.23937/2377-4630/1004 Received: August 15, 2014: Accepted: August 25, 2014: Published: September 11, ClinMed 2014 International Library Copyright: © 2014 Ellakany MH. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. DOI: 10.23937/2377-4630/1004 ISSN: 2377-4630

Table 1: Demographic data in the three studied groups. Group D Group M Group S P1 P2 P3 Age(years) 34.88 ± 10.16 34.88 ± 9.83 33.80 ± 9.81 0.500 0.368 0.350 Height(cm) 168.48 ± 6.22 168.40 ± 6.91 168.88 ± 6.00 0.483 0.410 0.397 Weight(Kg) 82.48 ± 11.69 87.48 ± 10.77 83.56 ± 11.52 0.128 0.355 0.110 Gender: Male 20 (80%) 21 (84%) 20 (80%) 0.712 - 0.712 Female 5 (20%) 4 (16%) 5 (20%) P1 is a comparison between group D and group M, p2 is a comparison between group D and group S and P3 is a comparison between group M and group S, - means that no applicable statistics because the same results in the two groups.

Table 2: Hypothrtmia, sensory-motor block duration, incidence and degree of shivering and surgery time among the three studied groups. Group D Group M Group S P1 P2 P3 Hypothermia 17 (68%) 16 (64%) 18 (72%) 0.765 0.757 0.403 Motor block duration 199.52 ± 58.61 210.96 ± 46.74 159.16 ± 40.79 0.247 0.009 0.000 Sensory block duration 277.56 ± 109.27 260.56 ± 73.92 206.60 ± 49.65 0.259 0.005 0.002 Incidence of shivering 5 (20%) 6 (24%) 23 (92%) 0.732 0.001 0.001 Degree of shivering 1.40 ± 0.55 1.50 ± 0.84 2.09 ± 0.79 - 0.108 0.061 Surgery time(minutes) 66.48 ± 19.57 65.92 ± 19.17 66.92 ± 14.43 0.450 0.464 0.418 P1 is a comparison between group D and group M, p2 is a comparison between group D and group S and P3 is a comparison between group M and group S, - means that no applicable statistics because the same results in the two groups. hypothermia. Preloading with 10 ml/kg of Ringer acetate solution was treated with 6 mg boluses. If patients developed was given to each patient. Spinal anesthesia was induced in the nausea and vomiting, 10 mg metoclopramide was administered semi-sitting position at either the L3-4 or L4-5 interspaces. Patients intravenously. Postoperatively, all patients were monitored, given were allocated into three equal groups, a dexmedetomidine (Group oxygen via a facemask and were covered with one layer of drapes and D, n=25), meperidine group (Group M, n = 25) or a saline control one cotton blanket. The post-anesthesia care unit temperature was group (Group S, n = 25) by a computer-generated randomization maintained at 25˚C to 26 ˚C and constant humidity. method. To detect a 50% reduction of shivering incidence, a sample Statistical analyses were performed using statistical package size of 18 patients per group was required (with an α = 0.05, β = 0.2, for social sciences (SPSS) version 15.0 for windows. Quantitative and a power of 80%). It was determined that 25 patients would be variables were compared between groups using Student’s t-test or included in each group with a power of 90%. The drug mixture was a Mann-Whitney U-test where appropriate. Within-group data for prepared by an investigator who was not otherwise involved in the core temperature were analyzed by using repeated-measures analysis study, he prepared syringes containing hyperbaric bupivacaine plus of variance followed by Bonferroni’s post-hoc testing. Within-group dexmedetomidine, meperidine or saline.; thus, the study was double- data for heart rate and mean arterial pressure were analyzed using blinded. The drug mixture was 12.5 mg hyperbaric bupivacaine 0.5% a Friedman test. Chi-square analysis was used for comparison of plus 5 mcg dexmedetomidine in 0.5 ml normal saline (Group D), categorical variables. The results are shown as median (range), mean 12.5 mg hyperbaric bupivacaine 0.5% plus 0.2 mg/Kg meperidine (¡SD), exact numbers or proportions are expressed as a percentage. hydrochloride 5% in 0.5 normal saline (Group M), and 12.5 mg p,0.05 was considered statistically significant. hyperbaric bupivacaine plus 0.5 ml of normal saline (Group S). A total volume of 3 ml of drug mixture (2.5 ml of hyperbaric bupivacaine Results 0.5% plus 0.5 ml of the study drugs (dexmedetomidine, meperidine or normal saline) was injected using a 27 G Quincke spinal needle. All patients completed the study. Supplemental oxygen (4 L/min) was delivered via a facemask during Regarding demographic data (age, height, weight, gender) and the operation. surgery duration, there were insignificant differences between the The incidence and intensity of shivering, blood pressure (BP), three studied groups (Table 1 and Table 2). heart rate, SpO2 and sublingual temperature were evaluated each Regarding hypothermia, it was recorded in 17 patients in 10 minutes for 180 minutes. Side effects like pruritus, nausea or dexmedetomidine group (68%), in 16 patients in meperidine group vomiting were recorded. Shivering was graded using the scale (64%), and in 18 patients in the control group (72%), with no described by Crossley and Mahajan [15] (0 = no shivering; 1 = significant differences between the three studied groupsTable ( 2). piloerection or peripheral vasoconstriction but no visible shivering; 2 = muscular activity in only one muscle group; 3 = muscular activity Regarding motor and sensory block duration, patients of group D in more than one muscle group but not generalized shivering; 4 = and M had longer duration than patients of group S, with significant shivering involving the whole body). Sublingual temperature was statistical difference (Table 2). monitored using an oral temperature probe with a monitor (Infinity Regarding shivering, patients of group D and M had less shivering Delta Monitor En, Draeger Medical S Sensory block was assessed by than patients of group S, with significant statistical difference (Table pinprick test with a 22 G hypodermic needle every minute during 2). the first 10 minutes, and then every 10 minutes, the motor block was assessed by modified bromage scale (0, no motor block; 1, hip Regarding the degree of shivering, patients of group D & M had blocked; 2, hip and knee blocked; 3, hip, knee, and, ankle blocked). lower degree of shivering than control group, but this difference did The presence of shivering was assessed by a blinded observer after the not reach statistical significance (Table 2). completion of subarachnoid drug injection. Sublingual temperature, Regarding bradycardia and hypotension, there were insignificant sensory block, motor block, incidence and severity of shivering were differences between the three studied groups (Table 3). recorded at 10-min intervals during the operation and in the recovery room. Side effects, such as hypotension, bradycardia, pruritus, nausea Regarding pruritus, pruritus developed in 5 patients in group M, and vomiting were recorded. If the patient’s heart rate fell below 50 1 patient in group D, and none in group S, with significant difference bpm, 0.5 mg intravenous atropine was administered. Hypotension between group M and the other 2 groups (Table 3). was defined as a decrease in the mean arterial pressure (MAP) of Regarding nausea and vomiting, 3 patients in group D and S, more than 20 % from baseline (baseline MAP was calculated from while 5 patients in group M developed nausea and vomiting with three measurements taken in the ward before surgery). Hypotension significant difference between group M and the other 2 groups (Table

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Table 3: Bradycardia, hypotension, pruritus, nausea and vomiting among the three studied groups. Group D Group M Group S P1 P2 P3 Bradycardia 4 (16%) 3 (12%) 3 (12%) 0.683 0.683 - Hypotension 6 (24%) 4 (16%) 6 (24%) 0.479 - 0.479 Pruritus 1 (4%) 5 (20%) 0 (0%) 0.081 0.312 0.018 Nausea&vomiting 3 (12%) 5 (20%) 3 (12%) 0.044 - 0.044 P1 is a comparison between group D and group M, p2 is a comparison between group D and group S and P3 is a comparison between group M and group S, - means that no applicable statistics because the same results in the two groups.

to core hypothermia during regional anesthesia: heat loss to the Group D Group M Group S environment, inhibition of central thermoregulatory control, and 120 redistribution of body heat [3,17,18,19]. When the body is exposed to a cold environment, the body temperature drops, and it worsens 100 when cold IV fluid or blood is administered without warming [20- 22]. Although one limitation of this study was measuring sublingual 80 temperature instead of core temperature of tympanic membrane, P A

M sublingual and axillary temperatures are thought to reflect core 60

ea n temperature with reasonable accuracy [23,24]. It has been reported, M 40 though, that axillary temperature does not correlate well with perioperative shivering and that the sublingual temperature reflects 20 changes in body temperature better than the axillary temperature [15]. The autonomic thermoregulatory responses to cold are shivering 0 and vasoconstriction. Normally, upon exposure to cold stress, the cutaneous vasculature constricts to reduce heat loss, metabolic heat production increases, and shivering begins in an effort to maintain core body temperature. Spinal anesthesia alters autonomic Figure 1: The mean values of mean arterial blood pressure and heart rate were comparable among the 3 groups. thermoregulatory responses by significantly decreasing the thresholds for vasoconstriction and shivering [18]. Shivering during spinal anesthesia is thought to occur due to a loss of thermoregulatory vasoconstriction and a loss of heat by heat redistribution from Group D Group M Group S core to peripheral parts of the body. However, the decrease in core 120 body temperature is not remarkable when compared with general anesthesia because spinal anesthesia causes only redistribution of 100 heat in the lower half of the body [3,18]. Regardless of its cause, shivering has the undesirable effects of markedly increasing oxygen 80 consumption and carbon dioxide production and decreasing R H 60 mixed venous oxygen saturation [16]. Cardiac output and minute ea n

M ventilation, as well as mean BP, increase to compensate for this 40 [25]. If these compensatory mechanisms fail, then hypoxemia may occur. These effects are often poorly tolerated by patients with limited 20 cardiac or pulmonary reserve. Therefore, shivering prevention is more important than its treatment in these patients. Adding a small amount 0 of meperidine during spinal anesthesia may aid high risk patients from developing shivering. In treating shivering, meperidine is much more effective than equipotent doses of other μ- , such Figure 2: The mean values of mean arterial blood pressure and heart as , alfentanil, sufentanil, or [26,27]. The anti- rate were comparable among the 3 groups. shivering property of meperidine is not fully understood. Several studies have suggested that the anti-shivering effect of meperidine is mediated by κ-opioid receptor agonist activity [10,28,29]. Also 3). meperidine suppresses the shivering threshold almost twice as Hypothermia was recorded in 17 patients (68%) in group D, 16 much as the vasconstriction threshold and this suppression in the patients (64%) in group M and 18 patients (72%) in group S, while shivering threshold appears to underlie the antishivering effect of shivering developed in 5 patients (20%) in group D, 6 patients meperidine [30]. Potential side effects of meperidine such as nausea, (24%) in group M and 23 patients (92%) in group S. Intrathecal vomiting, pruritus and hypotension must also be considered when dexmedetomidine and intathecal meperidine decreased the incidence administering meperidine [31]. of shivering and increased the sensory and motor block duration. Intrathecal meperidine caused more pruritus, nausea and vomiting Alpha-2 agonists are widely used nowadays in clinical than intrathecal dexmedetomidine (Table 3). practice of anesthesiology and intensive care. The α-2 receptor agonists are known to prevent shivering to a moderate extent without The mean values of mean arterial blood pressure and heart rate any associated respiratory depression as with other antishivering were comparable among the 3 groups. (Figures 1 and 2) Increments of atropine sulphate were given for bradycardia (4 patients in group drugs like meperidine [30,32]. Dexmedetomidine reduces shivering D, 3 patients in group M and group S) and increments of ephedrine by suppressing vasoconstriction and shivering thresholds [32,33]. were given for hypotension (6 patients in group D, 4 patients in group Alpha-2 adrenergic agonists decrease the central thermo-sensitivity M and 6 patients in group S). by suppressing the neuronal conductance [34]. This is mediated by the increased potassium conductance through G-coupled proteins which Discussion causes hyperpolarization of neurons [35-38]. Augmentation of neural suppression response is further mediated by restriction of calcium Shivering profoundly increases oxygen consumption (by entry into nerve cells which causes inhibition of neurotransmitter 200- 500%) and carbon dioxide production and decreases mixed release [38,39]. The increased accumulation of calcium ions on the venous oxygen saturation [5,16]. Three major factors contribute neuron’s surface in the posterior hypothalamus lowers the firing

• Page 3 of 5• Ellakany, Int J Anesthetic Anesthesiol 2014, 1:004 DOI: 10.23937/2377-4630/1004 ISSN: 2377-4630 rate of heat gain units by stabilizing the cell membrane [40]. α-2 9. Kranke P, Eberhart LH, Roewer N, Tramèr MR (2002) Pharmacological adrenergic agonists suppress the spontaneous firing rate of neurons in treatment of postoperative shivering: a quantitative systematic review of randomized controlled trials. Anesth Analg 94: 453-460. the and neurotransmitter mediated firing of neurons in the dorsal raphe nucleus when administered intravenously [41]. 10. Alfonsi P, Hongnat JM, Lebrault C, Chauvin M (1995) The effects of , fentanyl and lignocaine on postanaesthetic shivering. Anaesthesia 50: 214- All these central actions of α-2 agonists are possible due to a high 217. density of α-2 adrenoceptors in the hypothalamus and activation of 11. Wang JJ, Ho ST, Lee SC, Liu YC (1999) A comparison among nalbuphine, these receptors produces hypothermia by reduction of heat generated meperidine, and placebo for treating postanesthetic shivering. Anesth Analg by metabolic activity [42].Intrathecal DXM when combined with 88: 686-689. spinal bupivacaine prolongs the sensory block by depressing the 12. Roy JD, Girard M, Drolet P (2004) Intrathecal meperidine decreases shivering release of C-fibers transmitters and by hyperpolarization of post- during cesarean delivery under spinal anesthesia. Anesth Analg 98: 230- synaptic dorsal horn neurons [43-47]. Motor block prolongation by 234, table of contents. 2- adrenoreceptor agonists may result from binding these agonists to 13. Chen JC, Hsu SW, Hu LH, Hong YJ, Tsai PS, et al. (1993) [Intrathecal motor neurons in the dorsal horn of the spinal cord [48,49]. meperidine attenuates shivering induced by spinal anesthesia]. Ma Zui Xue Za Zhi 31: 19-24. The median incidence of shivering related to neuraxial anesthesia 14. Hong JY, Lee IH (2005) Comparison of the effects of intrathecal morphine in the control groups of 21 studies is 55 % (interquartile range of 40- and pethidine on shivering after Caesarean delivery under combined-spinal 64%) [1], which is much less than reported in this study(92%). In this epidural anaesthesia. Anaesthesia 60: 1168-1172. study, intrathecal meperidine decreased the incidence and severity of 15. Crossley AW, Mahajan RP (1994) The intensity of postoperative shivering is shivering compared with the control group, this was in agreement unrelated to axillary temperature. Anaesthesia 49: 205-207. with the study done by Chun DH et al. [50] who added intrathecal 16. De Witte J, Sessler DI (2002) Perioperative shivering: physiology and meperidine (0.2 mg/kg) to bupivacaine for spinal anesthesia during pharmacology. Anesthesiology 96: 467-484. 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