Efficacy and safety of prophylactic use of ketamine for prevention of postanesthetic shivering: A system review and meta analysis

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Due to the lack of high-quality evidence, it is difficult to draw a conclusion about optimal anti-shivering medication. The main purpose of this meta-analysis was to analyze and evaluate the efficacy and safety of prophylactic use of ketamine for preventing postanesthetic shivering. Methods We used a systematic approach, also known as meta-analysis, to further address postoperative shivering. We searched the following databases: Medline, Embase, and the Cochrane Central Register of Controlled Trails for randomized controlled trials. The primary outcome observed was the difference of the incidence rate of postanesthetic shivering between ketamine group and placebo group . The secondary outcomes were the sedation score and incidence of the side effects caused by ketamine and any other drugs utilized in the studies. Results In this meta-analysis, we analyzed a total of 16 trials including 1485 patients. Ketamine reduced the incidence rate of postanesthetic shivering compared to a placebo (odds ratio [OR]: 0.13, 95% confidence interval [CI]: 0.06 to 0.26, P＜0.01). Regarding side effects, there was no evident variability of the incidence of nausea and vomiting. Usage of ketamine was associated with a lower rate of hypotension and bradycardia when compared to a placebo. Hallucinations were more frequently observed in patients who received higher doses of ketamine. No significant difference was found in the incidence of postanesthetic shivering with ketamine versus other pharmacological interventions. Conclusions Ketamine can prevent postanesthetic shivering without severe side effects. However, ketamine shows no advantage over other anti-shivering drugs. Anesthesiology & Pain Medicine Postanesthetic shivering Anti-shivering Ketamine Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Postanesthetic shivering is a frequent complication of anesthesia, perhaps even aggravating pain. It is characterized by involuntary movement that may affect one or more muscle groups and is a very unpleasant and physiologically stressful experience. Postanesthetic shivering can interfere with electrocardiography (ECG) and oxygen saturation (SpO2) monitoring [ 1 ] . More importantly, it can increase oxygen consumption combined with minute ventilation and carbon dioxide production. Moreover, it is believed that postanesthetic shivering can increase mortality in the elderly and patients with coronary artery disease [ 2 ] . The aetiology of shivering is not sufficiently understood. Thermoregulatory and non-thermoregulatory factors may contribute to postoperative shivering including exposure to cold weather, inadequate pain control, and opioid withdrawal [ 3 ],[4] . The gold standard for treatment and prevention has not yet been defined. A variety of pharmacological treatments and methods to reduce postoperative shivering have been used including meperidine, alfentanil, tramadol, magnesium sulfate, ondansetron, dolasetron, and dexmedetomidine [5, 6, 7, 8, 9] . Ketamine has also been used as an anti-shivering drug. It is a non-competitive N-methy-D-aspartate (NMDA) receptor antagonist; it may prevent postanesthetic shivering by decreasing core-to-peripheral heat distribution. Although many published literatures have investigated the potential effects of ketamine for prevention of postanesthetic shivering, there is no consensus regarding the appropriateness of this drug. Thus, an evidence-based understanding of the benefits and risks of ketamine would identify its rational and optimal use. We conducted the meta-analysis to assess the efficacy and safety of ketamine for the prevention of shivering in patients undergoing various surgical procedures. Methods This meta-analysis was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Search strategy Two authors (Y. Z., A.M.) independently searched MEDLINE (2000 to March 2018), EMBASE (2000–2018), and the Cochrane Central Register of Controlled Trails (March 2018) with no language restrictions. By reviewing the references of the eligible articles, we identified additional studies relevant to our meta-analysis. The following search-term strategy was used: 1) shivering; 2) tremor; 3) shake; 4) hypothermia; 5) anesthesia; 6) postanesthetic; 7) postoperative; 8) surgery; 9) ketamine; 10) 1 or 2 or 3 or 4; 11) 5 or 6 or 7 or 8; 12) 9 and 10 and 11. Criteria for considering studies for this review The selection criteria were pre-established. Inclusion criteria were: (1) controlled clinical trial; (2) prophylactic use of ketamine compared with a placebo or other pharmacological interventions; (3) reported the incidence of postoperative shivering. Trials were not considered for the following reasons: (1) other anti-shivering drugs were also administrated during the anesthetic induction or maintenance period besides ketamine; (2) data from abstracts, letters, or reviews. We included any participants undergoing operative procedures with general or spinal anesthesia. The following outcomes were measured: (1) incidence of postanesthetic shivering; (2) sedation score; (3) incidence of other side effects. Data collection and analysis Two review authors (Y. Z., A.M.) independently screened all the titles and abstracts of the studies during the initial search to identify the included studies. After removing the duplicates, potentially relevant studies were retrieved in full-text version for the further assessment. We resolved any disagreement by discussion with another author (G. H. L) of our group. Data extraction was conducted by two authors (Y. Z., A.M.) independently using the data collection form established previously. The following data were collected from each study: primary author, publication year, anesthetic methods, demographic characteristics of participants, surgery types, comparisons, and other non-pharmacological warming methods. We recorded the number of patients experiencing shivering in each group for dichotomous data. We used the Review Manager software of the Cochrane Collaboration (RevMan 5.2) to perform the quantitative analysis. The results of dichotomous data are expressed as odds ratio (OR) and 95% confidence intervals (CIs). Heterogeneity testing was performed with Z score and X 2 statistical analysis; P<0.1 was considered to indicate heterogeneity. The fixed effect model or the random effect model were applied according to the heterogeneity of the study. A fixed effect model was used when I 2 <50%. We reported the results of included studies when the pooled analysis was not appropriate. Sensitivity and subgroup analysis were performed to explore the reason for the heterogeneity. Subgroup analysis was conducted based on the anesthetic methods, various doses of ketamine used, and the types of surgery. Publication bias was evaluated by Begg’s test using Stata 13.1 software (Stata, College Station, TX, USA). Results Search results and characteristics of the studies The flow chart (Figure 1) shows the process by which the selected studies were searched. A total of 361 potential articles were identified. We reviewed 30 full-text articles, after screening the titles and the abstracts. A total of 16 [10–25] studies including 1485 patients met our selection criteria and were included in the analysis (Table 1). In 15 trials, participants were adults. One trial [23] included children aged 5–12 years. Participants in seven trials [10,12,13,18,19,23,24] underwent operations under general anesthesia; participants in nine trials [11,14,15,16,17,20,21,22,25] were under spinal anesthesia. In 13 trials [10,12,14,15,16,17,18,19,20,21,22,23] ketamine was compared to placebo; in 4 trials [12,13,23,24] ketamine was compared to pethidine; in the other 4 trials [11,15,16,22] ketamine was compared to tramadol. Ketamine was also compared to ondansetron in 4 trials [10,15,17,21] . The administration time and routes were different among included trials. In 10 trials [11,14,15,16,17,20,21,22,23,25] the intervention drugs were given immediately after induction of anesthesia or intrathecal injection; in five trials [10,12,18,19,24] drugs were administrated before completion of the surgical procedure; in one trial [13] patients received study drugs before wound closure. Study drugs were given as an IV bolus in 14 trials [10–22,24] ; in two trials, patients received the study drugs epidurally [25] or intramuscularly [24] . In four trials [14,15,18,19] , patients underwent orthopedic surgery; patients in two studies [21,22] underwent abdominal surgery; patients in two studies [16,17] underwent cesarean section; patients in two studies [20,25] underwent urological surgery; in three trials, participants received ENT surgery [10] , endoscopic sinus surgery [12] , or tonsillectomy surgery [23] . Regarding measurement of intensity of shivering in a patient, 13 trials [10,13–17,19–25] utilized a scale with variation points ranging from 0–4: 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; 4 = shivering involving the whole body. One trial [12] applied a 0–3 scale for evaluating the intensity: 0 = no shivering; 1 = mild fasciculation of face or neck muscles; 2 = visible tremor involving more than one muscle; 3 = gross muscular activity involving the entire body. Two studies [11,18] did not assess the intensity of postanesthetic shivering. Assessment of the risk of bias in the included studies Two authors (Y. Z., A.M.) independently assessed the following domains using the Cochrane ‘Risk of bias’ tool: • Sequence generation • Allocation concealment • Blinding of participants, personnel • Blinding of outcome assessment • Incomplete outcome data • Selective outcome reporting • Other bias We completed ‘Risk of bias’ figures for each included study (Figure 2). See more details in Appendix. Publication bias Begg’s test showed that there was no publication bias for the primary outcome (p = 0.055). Effects of interventions Primary outcome Ketamine vs placebo The incidence of postanesthetic shivering was compared between ketamine and a placebo in 13 trials including 1166 patients (Figure 3). Ketamine has been shown to significantly decrease the incidence of shivering (pooled OR = 0.13; 95% CI: 0.06 to 0.26, P<0.00001). There was significant and prominent heterogeneity for this outcome (I 2 = 74%). Begg’s test showed that there was no risk of publication bias (P = 0.06). A subgroup analysis was performed to explore the evidence-based reason. In subgroup analysis of anesthetic methods, the heterogeneity was 67% in the GA (general anesthesia) group (Figure 4.). Sensitivity analysis was performed; a trial [22] was removed which utilized an air forced warmer intraoperatively, which showed a similar result favoring ketamine (pooled OR = 0.18; 95% CI: 0.09 to 0.37) and decreased heterogeneity (I 2 from 67% to 21%). Ketamine reduced the incidence of postanesthetic shivering in general anesthesia (pooled OR = 0.13; 95% CI: 0.06 to 0.26) and in spinal anesthesia (pooled OR = 0.08; 95% CI: 0.03 to 0.18). (Figure 5) shows the subgroup analysis based on the dose of ketamine used in the included trials. Ketamine reduced the incidence of postanesthetic shivering at the dose of 0.25mg/kg (pooled OR = 0.12; 95% CI: 0.03 to 0.52) and at the dose of 0.5mg/kg (pooled OR = 0. 14; 95% CI: 0.07 to 0.28). We performed a subgroup analysis based on the type of surgery, as this may influence the incidence of postanesthetic shivering (Figure 6). Ketamine significantly lowered the incidence of postanesthetic shivering in patients after orthopedic surgery (pooled OR = 0.32; 95% CI: 0.13 to 0.77). Among patients undergoing abdominal, cesarean section, urological, ENT or endoscopic surgery, ketamine also reduced the incidence of postanesthetic shivering. Ketamine vs other pharmacological interventions A total of four studies [12,13,23,24] investigated the effect of ketamine on the prevention of shivering compared with pethidine. The pooled analysis showed a definite difference in favor of pethidine (pooled OR = 4.38; 95% CI: 1.76 to 10.92). No significant difference in postanesthetic shivering was found between ketamine and other pharmacological interventions (Figure 7). Secondary outcomes Ketamine vs placebo Except for the other side effects (hypotension, bradycardia, hallucination), there was no significant difference in the incidence of postoperative nausea and vomiting (PONV) between ketamine and the placebo (pooled RR = 0.72; 95% CI: 0.48 to 1.08) (Table 3). Ketamine reduced the incidence of hypotension and bradycardia compared with the placebo (pooled RR = 0.28; 95% CI: 0.17 to 0.47; pooled RR = 0.18; 95% CI: 0.05 to 0.65). The incidence of hallucination was more significant and prevalent in the patients who received 0.5mg/kg ketamine (Table 4); there was only one episode of hallucination in patients receiving 0.25mg/kg. Seven studies [14,15,16,20,21,22,25] reported the sedation score of patients on a five-point scale: 1 = fully awake and oriented, 2 = drowsy, 3 = eyes closed but arousable to command, 4 = eyes closed but arousable to mild physical stimulation, and 5 = eyes closed but unarousable to mild physical stimulation. A pooled analysis was not performed because of the lack of uniform sedation score scales in the trials. All of these studies showed that the patients in the ketamine group were more sedated compared to the placebo group. Five trials [14,16,17,19,23] reported a significant decrease in core temperature in both the ketamine and placebo groups compared to the baseline temperature of participants. However, it was not significant between groups, at any time point. Three trials [20,21,22] reported a significant difference in core temperature between ketamine and the placebo; a greater decrease in temperature was found in the placebo group. Ketamine vs other pharmacological interventions No significant difference was found in the incidence of PONV between ketamine and pethidine (pooled OR = 0.88; 95% CI: 0.38 to 2.07). Compared to tramadol, the difference in the incidence of PONV and hypotension is not significant (OR = 0.57; 95% CI: 0.18 to 178; OR = 0.90; 95% CI: 0.36 to 2.24). The incidence of PONV was higher in the ketamine group than the ondansetron group (OR = 4.49; 95% CI: 1.24 to 16.21). However, ketamine showed a lower incidence of hypotension compared to ondansetron (OR = 0.09; 95% CI: 0.00 to 3.23). Core temperature changes were reported graphically; there was no significant difference between ketamine and other pharmacological interventions. Summary of findings and quality of evidence The Summary of findings with GRADE recommendations are shown in Table 2. Discussion In the present study, we compared different randomized controlled trials to identify the beneficial aspects of ketamine. We compared the usage of ketamine and its relevance in anaesthetic shivering. In total, 16 studies including 1485 patients were analysed. Ketamine was first synthesized in the early 1960s as a safe alternative to phencyclidine [26] . It is a non-competitive -NMDA receptor antagonist with an effect of thermoregulation. Other than being a competitive NMDA receptor antagonist, ketamine also acts as an opioid agonist [27] . Further, it can cause blockage of amine uptake in the descending inhibitory monoaminergic pain pathways, having a local anaesthetic action and interacting with the muscarinic receptors [28] . In contrast, even at sub-anaesthetic doses, ketamine might cause a dissociative state, characterised by a sense of detachment from one’s physical body and the external world (depersonalization and derealization). Ketamine probably controls shivering by acting on non-shivering thermogenesis [29] . Ketamine is predominantly utilized as an anaesthetic agent that induces analgesia but for a long time it has been criticized for some of its side effects which include the induction of a psychedelic state causing agitation and hallucinations [30] . The key findings of our analysis are as follows. Ketamine exposure was relatively better in reducing the occurrence of postanaesthetic shivering compared to placebo. Compared with tramadol and ondansetron, ketamine slightly lowered the incidence of postanaesthetic shivering although not significantly. The effect of ketamine on postanaesthetic shivering remained equally beneficial for both spinal and general types of anaesthesia. A dose of 0.5 mg/kg had an advance effect compared to 0.25 mg/kg on the postanaesthetic shivering rate. The effect remained constant for all types of surgical procedures including orthopaedic surgery, laparotomy, caesarean section, urological, ENT, and endoscopic surgeries. Compared to ketamine, pethidine showed a quicker responsive rate. However, sufficient data was not available in other studies to show any advantage of other pharmacological interventions. Furthermore, we evaluated the side effects of the anaesthetic drugs and the role of ketamine in preventing or overcoming the effects. Moreover, the efficacy of ketamine was compared with a placebo. The side effects observed in the trials were nausea, vomiting, hypotension, bradycardia, and hallucinations. Ketamine showed a favourable outcome in reducing the incidence rate of hypotension and bradycardia as ketamine causes dose dependent direct stimulation of the CNS which leads to increased sympathetic nervous system stimulation followed by increased systemic blood pressure and heart rate. However, there was no effect of ketamine in decreasing the incidence rate of nausea and vomiting as compared to placebo. As ketamine is known to have a hallucinogenic effect, it is considered to have a potential role in glutamatergic signalling in psychosis; therefore, the usage of ketamine is suggested to be associated with auditory and verbal hallucinations. In our comparative study, we also found that the rate of occurrence of hallucination episodes was much higher in patients receiving a ketamine dose of 0.5 mg/kg compared to a lower dose of 0.25 mg/kg. The hallucinogenic effect of ketamine was evident when compared with the placebo drugs, for which there was no incidence of hallucinations reported in any of the trials. Ketamine can cause sedation in postoperative patients and deep sedation is considered to be a severe adverse event. However, for those experiencing shivering, mild sedation may prevent them from hurting themselves. In our study, we paid special attention to the sedation score of patients, although pooled analysis was not conducted because of various sedation scales. We found that mild to moderate sedation was more commonly seen in patients receiving different doses of ketamine. Besides various pharmacological interventions above, we noticed that active warming for elective caesarean delivery reduced the incidence of postoperative shivering and provided more stable perioperative temperature change [31] . Accumulating evidence has shown that the active warming method including electric heating, water-circulating garments, forced-air, and radiant heating is effective in preventing post-anaesthetic shivering. The current American Society of Anesthesiologists Task Force on Postanesthetic Care guidelines recommend forced-air warming as a common method to reduce shivering in the perioperative setting [32] . Future research should focus on combinations of pharmacological interventions with non-pharmacological methods to better solve this problem. The major limitation of our study is that we could not study the hemodynamical changes related to ketamine usage as there were no standard criteria being followed by the trials causing irrelevancy and uneven data for comparing and evaluating precise outcomes in this regard. Second, the sample size of included trials was relatively small which may decrease generalisability of our conclusions. Third, the evidence level for our outcomes was low or very low. However, we believe that our study is of value because it provided clear evidence of the benefit of prophylactic ketamine intervention for preventing post-anaesthetic shivering which may be helpful in clinical practice. Conclusions In this meta-analysis, we assessed various aspects of ketamine usage in controlling post-anaesthetic shivering. We found that ketamine reduced the incidence rate of shivering compared to the placebo. Although it is beneficial, it did not show any superiority over other pharmacological interventions. Ketamine is of clinical value, but further studies should be performed on a wider scale to determine more emphasized results. Furthermore, larger clinical trials investigating the combination of different anti-shivering regimens are warranted. Abbreviations ECG: electrocardiography; ENT : ear-nose-throat ; NMDA: N-methy-D-aspartate; PONV: postoperative nausea and vomiting; PRISMA: Reporting Items for Systematic Reviews and Meta-Analysis; SpO2: oxygen saturation; CNS: central nervous system Declarations Ethics approval and consent to participate: Not applicable Consent for publication: Not applicable Availability of data and materials: The datasets used in the analysis was collected by online search, and the datasets analyzed in the current study are available from the corresponding author on reasonable request. Competing interests: The authors declare that they have no competing interests. Funding: Support by the National Natural Science Foundation of China Grant Nos. 81070888 and 81230025 (to J-LC), the Scientific Innovation Group of “Qing Lan Project” of Jiangsu Province (to J-LC), the Jiangsu Provincial Special Program of Medical Science Grant No. BL2014029 (to J-LC); the Priority Academic Program Development of Jiangsu Higher Education Institutions (to J-LC). Authors’ contributions: Study design: J. L. C., Y. H., Y. Z., A.M Writing of the manuscript: J. L. C., Y. H., Y. Z., A.M. Data analysis: Y. Z., M. A. Acknowledgements: Not applicable References Insler SR, Sessler DI. Perioperative thermoregulation and temperature monitoring. Anesthesiology clinics 2006; 24: 823–37 Alfonsi P. Postanaesthetic Shivering. Drugs 2001; 61: 2193–205 Horn EP, Schroeder F, Wilhelm S, et al. Postoperative pain facilitates nonthermoregulatory tremor. Anesthesiology 1999; 91: 979–84 Lenhardt R. The effect of anesthesia on body temperature control[J]. Front Biosci, 2010, 2:1145–1154. 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A comparative study on the prophylactic effects of ketamine, dexamethasone, and pethidine in preventing postoperative shivering. Journal of Research in Medical Sciences 2012; 17: S175-S81 Han DY, Jeong HJ, Lee C, Choi DH. The Efficacy of Epidural Ketamine on Shivering during Transurethral Resection of the Prostate under Epidural Anesthesia. International neurourology journal 2010; 14: 105–11 Niesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. British Journal of Clinical Pharmacology 2014; 77(2):357–67 Dar A M, Qazi S M, Sidiq S. A placebo-controlled comparison of ketamine with pethidine for the prevention of postoperative shivering. Southern African Journal of Anaesthesia & Analgesia 2013; 18:340–343 Aroni F, Iacovidou N, Dontas I, et al. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug[J]. Journal of Clinical Pharmacology, 2013, 49(8):957–964. Sharma DR, Thakur JR. Ketamine and shivering. Anaesthesia 2010; 45: 252–3 De Witte J, Sessler DI. Perioperative shivering: physiology and pharmacology. Anesthesiology 2002; 96:467–84 Tables Table1.Summary of Characteristics of Included Studies Study ID Participants Surgery Types Anesthesia Methods Comparison Non-pharmacological Warming Methods Control Group Intervention Group Sagir 2007 160 patients 18-65yr urological surgery SA C(40): saline iv K(40):ketamine 0.5mg/kg iv;G(40):granisetron 3mg,iv;KG(40)ketamine 0.25/kg+granisetron 1.5mg iv All patients were covered with drapes and a cotton blanket .Fluids were preheated to 37 o c Honarmand 2008 120 patients 18-60yr orthopaedic surgery SA C(30) saline iv; K(30) ketamine 0.5mg/kg iv; M(30) midazolam 75µg/kg iv; KM(30) ketamine 0. 25mg/kg+midazolam 37.5µg/kg iv Fluids were preheated to 37 o c Zahra 2008 120 patients 5-12yr tonsillectomy surgery GA C(40):saline K(40):ketamine 1mg/kg;P(40):pethidine 0.5mg/kg None. Han 2010 93 patients 51-78yr transurethral resection of the prostate SA C(31): epidural 0.75% ropivacaine K1(32): epdural ketamine 0.2mg/kg+0.75%ropivacaine; K2(30): epidural ketamine 0.4mg/kg+0.75%ropivacaine None Shakya 2010 120 patients Lower abdominal surgery SA C(40):saline iv K(40): ketamine 0.25mg/kg iv;O(40):ondansetron 4mg iv Patients were covered with standard single blanket Ayatollahi 2011 120 patients 20-50yr endoscopic sinus surgery GA C(30): saline iv K1(30): 0.3mg/kg iv; K2(30) : 0.5mg/kg iv; M(30): meperidine 0.4mg/kg iv Patients were covered with a cotton blanket Norouzi 2011 120 patients 18-65yr elective orthopedic surgery GA C(30):saline iv K1(30):ketamine 0.125mg/kg iv;K2(30):ketamine 0.25mg/kg iv;K3(30):ketamine 0.5mg/kg iv None Wason 2012 200 patients 18-65yr ower abdominal or lower limb surgery SA C(50):saline iv K(50):ketamine 0.5mg/kg iv;C(50):clonidine 75mcg;T(50):tramadol 0.5mg/kg iv Fluids were preheated to 37 o c Zavareh 2012 135 patients 18-70yr elective surgery GA K(45):ketamine 0.5mg/kg iv; P(45):pethidine 0.5mg/kg;D(45):dexamethasone,0.6mg/kg None Abdelhalim 2014 120 patients 18-45yr ENT surgery GA C(30): saline iv O(30): ondansetron 8mg iv; K(30): ketamine 0.5mg/kg iv; OK(30)ondansetron 8mg+ketamine 0.25mg/kg iv None Petskul 2016 183 patients 18-65yr orthopedic surgery GA C(92):saline iv K(91):ketamine 0.25mg/kg iv All patients were warmed by air force warmer Mohtadi 2016 117 patients 18-40yr cesarean section SA C(39):saline iv K(39):ketamine 0.25mg/kg,iv;O(39):ondansetron 4mg,iv None Hasannasab 2016 120 patients 20-45yr gynecologic surgery GA K(40): ketamine 0.25mg/kg iv; M(40): meperidine 20mg iv ; D(40): doxapram 0.25mg/kg iv Patients were covered with a standard blanket Lakhe 2017 120 patients 18-65 years gynecological and orthopedic surgery SA C(30):saline,iv T(30):tramadol 0.5mg/kg iv O(30):ondansetron 4mg,iv;K(30):ketamine 0.25mg/kg iv Patients were covered with drapes Lema 2017 123 patients 18-39yr cesarean section SA C(41):saline iv K(41):ketamine 0.2mg/kg iv;T(41): tramadol 0.5mg/kg iv Patients were covered with drapes Abbreviations: yr, years; GA, general anesthesia; SA, spinal anesthesia; C, control;O, ondansetron; T, t ramadol; M, meperidine; D, doxapram; G, granisetron; CL, clonidine; P, pethidine. Table 2. Summary of findings with GRADE recommendations. ketamine for postoperative shivering Patient or population: patients with postoperative shivering Settings: hospitals Intervention: ketamine Outcomes Illustrative comparative risks* (95% CI) Relative effect (95% CI) No of Participants (studies) Quality of the evidence (GRADE) Comments Assumed risk Corresponding risk Control Ketamine Incidence of shivering Study population OR 0.13 (0.06 to 0.26) 1166 (13 studies) ⊕⊕ ⊝⊝ low 1 468 per 1000 103 per 1000 (50 to 186) Moderate 500 per 1000 115 per 1000 (57 to 206) Nausea and vomitting Study population OR 0.7 (0.44 to 1.12) 986 (11 studies) ⊕⊕ ⊝⊝ low 1 123 per 1000 89 per 1000 (58 to 136) Moderate 125 per 1000 91 per 1000 (59 to 138) Hypotension Study population OR 0.3 (0.18 to 0.49) 573 (7 studies) ⊕ ⊝⊝⊝ very low 1 225 per 1000 80 per 1000 (50 to 125) Moderate 200 per 1000 70 per 1000 (43 to 109) Bradycardia Study population OR 0.14 (0.04 to 0.52) 193 (2 studies) ⊕ ⊝⊝⊝ very low 1 136 per 1000 22 per 1000 (6 to 76) Moderate 165 per 1000 27 per 1000 (8 to 93) Hallucination Study population OR 4.41 (1.14 to 17.07) 423 (5 studies) ⊕ ⊝⊝⊝ very low 1 0 per 1000 0 per 1000 (0 to 0) Moderate 0 per 1000 0 per 1000 (0 to 0) *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; OR: Odds ratio; GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. Table 3. Comparisons of incidence of other side effects Side effccts Number of studies Ketamine Placebo Events/Total Events/Total Odds Ratio (95% CI) Nausea and vomitting 11 48/523 57/463 0.70 [0.44, 1.12] Hypotension 6 23/302 61/271 0.30 [0.18, 0.49] Bradycardia 2 3/112 11/81 0.14 [0.04, 0.52] Hallucination 5 16/272 0/151 4.41 [1.14, 17.07] Abbreviations: CI, confidence interval. Table 4. Episodes of hallucination based on the dose of ketamine. Study ID Dose of ketamine Ketamine Placebo Events/Total Events/Total Honarmand 2008 0.5mg/kg 3/30 0/30 Han 2010 0.4mg/kg 2/30 0/31 Norouzi 2011 0.25mg/kg 1/30 0/30 Norouzi 2011 Ayatollahi 2011 Abdelhalim 2014 0.5mg/kg 0.5mg/kg 0.5mg/kg 4/30 3/30 1/30 0/30 0/30 0/30 Supplementary Files PRISMAchecklist.doc 1.grd Cite Share Download PDF Status: Published Journal Publication published 30 Dec, 2019 Read the published version in BMC Anesthesiology → Version 3 posted Editorial decision: Minor revision 25 Nov, 2019 Review # 1 received at journal 16 Nov, 2019 Editor assigned by journal 13 Nov, 2019 Reviewers invited by journal 13 Nov, 2019 Reviewer # 1 agreed at journal 13 Nov, 2019 Editor invited by journal 12 Nov, 2019 Submission checks completed at journal 07 Nov, 2019 You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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CI, confidence interval; GA, genaral anesthesia; SA, spinal anesthesia.","description":"","filename":"fig4.png","url":"https://assets-eu.researchsquare.com/files/47e0d480-67ce-4bf7-b76e-a11d038660d0/v3/fig4.png"},{"id":167011,"identity":"d3b97057-7ccf-4cca-a14e-59d2dc88366e","added_by":"auto","created_at":"2019-11-19 13:35:49","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":424515,"visible":true,"origin":"","legend":"Result of subgruop analysis according to different doses of ketamine administrated. 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CI indicates confidence interval.","description":"","filename":"fig6.png","url":"https://assets-eu.researchsquare.com/files/47e0d480-67ce-4bf7-b76e-a11d038660d0/v3/fig6.png"},{"id":167013,"identity":"7a405c59-4c27-4cf9-bf36-44fd512f3b54","added_by":"auto","created_at":"2019-11-19 13:35:49","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":809507,"visible":true,"origin":"","legend":"Forest plots of effects of ketamine on postanesthesia shivering compared with other study drugs. CI indicates confidence interval.","description":"","filename":"fig7all.png","url":"https://assets-eu.researchsquare.com/files/47e0d480-67ce-4bf7-b76e-a11d038660d0/v3/fig7 all.png"},{"id":13479494,"identity":"78b90f77-e532-4175-81c9-886257d84a7e","added_by":"auto","created_at":"2021-09-16 21:39:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2237192,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1284/v3/074800d5-d76f-4d44-b232-31e9c580f828.pdf"},{"id":167007,"identity":"c43404e3-6c10-4643-8ae3-c4a495764c3c","added_by":"auto","created_at":"2019-11-19 13:35:48","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":55296,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAchecklist.doc","url":"https://assets-eu.researchsquare.com/files/47e0d480-67ce-4bf7-b76e-a11d038660d0/v3/PRISMA checklist.doc"},{"id":167005,"identity":"6613a382-cd4b-4c6c-beb1-e6a7262edf3b","added_by":"auto","created_at":"2019-11-19 13:35:48","extension":"grd","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":16384,"visible":true,"origin":"","legend":"","description":"","filename":"1.grd","url":"https://assets-eu.researchsquare.com/files/47e0d480-67ce-4bf7-b76e-a11d038660d0/v3/1.grd"}],"financialInterests":"","formattedTitle":"Efficacy and safety of prophylactic use of ketamine for prevention of postanesthetic shivering: A system review and meta analysis","fulltext":[{"header":"Background","content":"\u003cp\u003ePostanesthetic shivering is a frequent complication of anesthesia, perhaps even aggravating pain. It is characterized by involuntary movement that may affect one or more muscle groups and is a very unpleasant and physiologically stressful experience. Postanesthetic shivering can interfere with electrocardiography (ECG) and oxygen saturation (SpO2) monitoring\u003csup\u003e [\u003c/sup\u003e1\u003csup\u003e]\u003c/sup\u003e. More importantly, it can increase oxygen consumption combined with minute ventilation and carbon dioxide production. Moreover, it is believed that postanesthetic shivering can increase mortality in the elderly and patients with coronary artery disease\u003csup\u003e [\u003c/sup\u003e2\u003csup\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe aetiology of shivering is not sufficiently understood. Thermoregulatory and non-thermoregulatory factors may contribute to postoperative shivering including exposure to cold weather, inadequate pain control, and opioid withdrawal\u003csup\u003e [\u003c/sup\u003e3\u003csup\u003e],[4]\u003c/sup\u003e. The gold standard for treatment and prevention has not yet been defined. A variety of pharmacological treatments and methods to reduce postoperative shivering have been used including meperidine, alfentanil, tramadol, magnesium sulfate, ondansetron, dolasetron, and dexmedetomidine\u003csup\u003e [5, 6, 7, 8, 9]\u003c/sup\u003e. Ketamine has also been used as an anti-shivering drug. It is a non-competitive N-methy-D-aspartate (NMDA) receptor antagonist; it may prevent postanesthetic shivering by decreasing core-to-peripheral heat distribution. Although many published literatures have investigated the potential effects of ketamine for prevention of postanesthetic shivering, there is no consensus regarding the appropriateness of this drug. Thus, an evidence-based understanding of the benefits and risks of ketamine would identify its rational and optimal use. We conducted the meta-analysis to assess the efficacy and safety of ketamine for the prevention of shivering in patients undergoing various surgical procedures.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis meta-analysis was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.\u003c/p\u003e\n\u003cp\u003eSearch strategy\u003c/p\u003e\n\u003cp\u003eTwo authors (Y. Z., A.M.) independently searched MEDLINE (2000 to March 2018), EMBASE (2000–2018), and the Cochrane Central Register of Controlled Trails (March 2018) with no language restrictions. By reviewing the references of the eligible articles, we identified additional studies relevant to our meta-analysis. The following search-term strategy was used:\u003c/p\u003e\n\u003cp\u003e1) shivering; 2) tremor; 3) shake; 4) hypothermia; 5) anesthesia; 6) postanesthetic; 7) postoperative; 8) surgery; 9) ketamine; 10) 1 or 2 or 3 or 4; 11) 5 or 6 or 7 or 8; 12) 9 and 10 and 11.\u003c/p\u003e\n\u003cp\u003eCriteria for considering studies for this review\u003c/p\u003e\n\u003cp\u003eThe selection criteria were pre-established. Inclusion criteria were: (1) controlled clinical trial; (2) prophylactic use of ketamine compared with a placebo or other pharmacological interventions; (3) reported the incidence of postoperative shivering. Trials were not considered for the following reasons: (1) other anti-shivering drugs were also administrated during the anesthetic induction or maintenance period besides ketamine; (2) data from abstracts, letters, or reviews. We included any participants undergoing operative procedures with general or spinal anesthesia. The following outcomes were measured: (1) incidence of postanesthetic shivering; (2) sedation score; (3) incidence of other side effects.\u003c/p\u003e\n\u003cp\u003eData collection and analysis\u003c/p\u003e\n\u003cp\u003eTwo review authors (Y. Z., A.M.) independently screened all the titles and abstracts of the studies during the initial search to identify the included studies. After removing the duplicates, potentially relevant studies were retrieved in full-text version for the further assessment. We resolved any disagreement by discussion with another author (G. H. L) of our group.\u003c/p\u003e\n\u003cp\u003eData extraction was conducted by two authors (Y. Z., A.M.) independently using the data collection form established previously. The following data were collected from each study: primary author, publication year, anesthetic methods, demographic characteristics of participants, surgery types, comparisons, and other non-pharmacological warming methods. We recorded the number of patients experiencing shivering in each group for dichotomous data.\u003c/p\u003e\n\u003cp\u003eWe used the Review Manager software of the Cochrane Collaboration (RevMan 5.2) to perform the quantitative analysis. The results of dichotomous data are expressed as odds ratio (OR) and 95% confidence intervals (CIs). Heterogeneity testing was performed with Z score and X\u003csup\u003e2\u003c/sup\u003e statistical analysis; P\u0026lt;0.1 was considered to indicate heterogeneity. The fixed effect model or the random effect model were applied according to the heterogeneity of the study. A fixed effect model was used when I\u003csup\u003e2\u003c/sup\u003e\u0026lt;50%. We reported the results of included studies when the pooled analysis was not appropriate. Sensitivity and subgroup analysis were performed to explore the reason for the heterogeneity. Subgroup analysis was conducted based on the anesthetic methods, various doses of ketamine used, and the types of surgery. Publication bias was evaluated by Begg’s test using Stata 13.1 software (Stata, College Station, TX, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eSearch results and characteristics of the studies\u003c/p\u003e\n\u003cp\u003eThe flow chart (Figure 1) shows the process by which the selected studies were searched. A total of 361 potential articles were identified. We reviewed 30 full-text articles, after screening the titles and the abstracts. A total of 16\u003csup\u003e[10–25]\u003c/sup\u003e studies including 1485 patients met our selection criteria and were included in the analysis (Table 1).\u003c/p\u003e\n\u003cp\u003eIn 15 trials, participants were adults. One trial \u003csup\u003e[23] \u003c/sup\u003eincluded children aged 5–12 years. Participants in seven trials\u003csup\u003e [10,12,13,18,19,23,24]\u003c/sup\u003e underwent operations under general anesthesia; participants in nine trials\u003csup\u003e [11,14,15,16,17,20,21,22,25]\u003c/sup\u003e were under spinal anesthesia. In 13 trials\u003csup\u003e[10,12,14,15,16,17,18,19,20,21,22,23]\u003c/sup\u003e ketamine was compared to placebo; in 4 trials\u003csup\u003e[12,13,23,24] \u003c/sup\u003eketamine was compared to pethidine; in the other 4 trials\u003csup\u003e[11,15,16,22]\u003c/sup\u003e ketamine was compared to tramadol. Ketamine was also compared to ondansetron in 4 trials\u003csup\u003e[10,15,17,21]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe administration time and routes were different among included trials. In 10 trials\u003csup\u003e [11,14,15,16,17,20,21,22,23,25]\u003c/sup\u003e the intervention drugs were given immediately after induction of anesthesia or intrathecal injection; in five trials\u003csup\u003e [10,12,18,19,24]\u003c/sup\u003e drugs were administrated before completion of the surgical procedure; in one trial\u003csup\u003e [13]\u003c/sup\u003e patients received study drugs before wound closure. Study drugs were given as an IV bolus in 14 trials\u003csup\u003e [10–22,24]\u003c/sup\u003e; in two trials, patients received the study drugs epidurally\u003csup\u003e [25]\u003c/sup\u003e or intramuscularly\u003csup\u003e [24]\u003c/sup\u003e. In four trials\u003csup\u003e [14,15,18,19]\u003c/sup\u003e, patients underwent orthopedic surgery; patients in two studies\u003csup\u003e [21,22]\u003c/sup\u003e underwent abdominal surgery; patients in two studies\u003csup\u003e[16,17]\u003c/sup\u003e underwent cesarean section; patients in two studies\u003csup\u003e[20,25]\u003c/sup\u003e underwent urological surgery; in three trials, participants received ENT surgery\u003csup\u003e[10]\u003c/sup\u003e, endoscopic sinus surgery\u003csup\u003e[12]\u003c/sup\u003e, or tonsillectomy surgery\u003csup\u003e[23]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eRegarding measurement of intensity of shivering in a patient, 13 trials\u003csup\u003e [10,13–17,19–25] \u003c/sup\u003eutilized a scale with variation points ranging from 0–4: 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; 4 = shivering involving the whole body. One trial\u003csup\u003e [12]\u003c/sup\u003e applied a 0–3 scale for evaluating the intensity: 0 = no shivering; 1 = mild fasciculation of face or neck muscles; 2 = visible tremor involving more than one muscle; 3 = gross muscular activity involving the entire body. Two studies\u003csup\u003e [11,18]\u003c/sup\u003e did not assess the intensity of postanesthetic shivering.\u003c/p\u003e\n\u003cp\u003eAssessment of the risk of bias in the included studies\u003c/p\u003e\n\u003cp\u003eTwo authors (Y. Z., A.M.) independently assessed the following domains using the Cochrane ‘Risk of bias’ tool:\u003c/p\u003e\n\u003cp\u003e• Sequence generation\u003c/p\u003e\n\u003cp\u003e• Allocation concealment\u003c/p\u003e\n\u003cp\u003e• Blinding of participants, personnel\u003c/p\u003e\n\u003cp\u003e• Blinding of outcome assessment\u003c/p\u003e\n\u003cp\u003e• Incomplete outcome data\u003c/p\u003e\n\u003cp\u003e• Selective outcome reporting\u003c/p\u003e\n\u003cp\u003e• Other bias\u003c/p\u003e\n\u003cp\u003eWe completed ‘Risk of bias’ figures for each included study (Figure 2). See more details in Appendix.\u003c/p\u003e\n\u003cp\u003ePublication bias\u003c/p\u003e\n\u003cp\u003eBegg’s test showed that there was no publication bias for the primary outcome (p = 0.055).\u003c/p\u003e\n\u003cp\u003eEffects of interventions\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePrimary outcome\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eKetamine vs placebo \u003c/em\u003eThe incidence of postanesthetic shivering was compared between ketamine and a placebo in 13 trials including 1166 patients (Figure 3). Ketamine has been shown to significantly decrease the incidence of shivering (pooled OR = 0.13; 95% CI: 0.06 to 0.26, P\u0026lt;0.00001). There was significant and prominent heterogeneity for this outcome (I\u003csup\u003e2\u003c/sup\u003e = 74%). Begg’s test showed that there was no risk of publication bias (P = 0.06). A subgroup analysis was performed to explore the evidence-based reason. In subgroup analysis of anesthetic methods, the heterogeneity was 67% in the GA (general anesthesia) group (Figure 4.). Sensitivity analysis was performed; a trial\u003csup\u003e[22]\u003c/sup\u003e was removed which utilized an air forced warmer intraoperatively, which showed a similar result favoring ketamine (pooled OR = 0.18; 95% CI: 0.09 to 0.37) and decreased heterogeneity (I\u003csup\u003e2\u003c/sup\u003e from 67% to 21%). Ketamine reduced the incidence of postanesthetic shivering in general anesthesia (pooled OR = 0.13; 95% CI: 0.06 to 0.26) and in spinal anesthesia (pooled OR = 0.08; 95% CI: 0.03 to 0.18). (Figure 5) shows the subgroup analysis based on the dose of ketamine used in the included trials. Ketamine reduced the incidence of postanesthetic shivering at the dose of 0.25mg/kg (pooled OR = 0.12; 95% CI: 0.03 to 0.52) and at the dose of 0.5mg/kg (pooled OR = 0. 14; 95% CI: 0.07 to 0.28). We performed a subgroup analysis based on the type of surgery, as this may influence the incidence of postanesthetic shivering (Figure 6). Ketamine significantly lowered the incidence of postanesthetic shivering in patients after orthopedic surgery (pooled OR = 0.32; 95% CI: 0.13 to 0.77). Among patients undergoing abdominal, cesarean section, urological, ENT or endoscopic surgery, ketamine also reduced the incidence of postanesthetic shivering.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eKetamine vs other pharmacological interventions \u003c/em\u003eA total of four studies\u003csup\u003e [12,13,23,24]\u003c/sup\u003e investigated the effect of ketamine on the prevention of shivering compared with pethidine. The pooled analysis showed a definite difference in favor of pethidine (pooled OR = 4.38; 95% CI: 1.76 to 10.92). No significant difference in postanesthetic shivering was found between ketamine and other pharmacological interventions (Figure 7).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSecondary outcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eKetamine vs placebo\u003c/em\u003e Except for the other side effects (hypotension, bradycardia, hallucination), there was no significant difference in the incidence of postoperative nausea and vomiting (PONV) between ketamine and the placebo (pooled RR = 0.72; 95% CI: 0.48 to 1.08) (Table 3). Ketamine reduced the incidence of hypotension and bradycardia compared with the placebo (pooled RR = 0.28; 95% CI: 0.17 to 0.47; pooled RR = 0.18; 95% CI: 0.05 to 0.65). The incidence of hallucination was more significant and prevalent in the patients who received 0.5mg/kg ketamine (Table 4); there was only one episode of hallucination in patients receiving 0.25mg/kg. Seven studies\u003csup\u003e [14,15,16,20,21,22,25]\u003c/sup\u003e reported the sedation score of patients on a five-point scale: 1 = fully awake and oriented, 2 = drowsy, 3 = eyes closed but arousable to command, 4 = eyes closed but arousable to mild physical stimulation, and 5 = eyes closed but unarousable to mild physical stimulation. A pooled analysis was not performed because of the lack of uniform sedation score scales in the trials. All of these studies showed that the patients in the ketamine group were more sedated compared to the placebo group. Five trials\u003csup\u003e [14,16,17,19,23]\u003c/sup\u003e reported a significant decrease in core temperature in both the ketamine and placebo groups compared to the baseline temperature of participants. However, it was not significant between groups, at any time point. Three trials\u003csup\u003e [20,21,22]\u003c/sup\u003e reported a significant difference in core temperature between ketamine and the placebo; a greater decrease in temperature was found in the placebo group.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eKetamine vs other pharmacological interventions \u003c/em\u003eNo significant difference was found in the incidence of PONV between ketamine and pethidine (pooled OR = 0.88; 95% CI: 0.38 to 2.07). Compared to tramadol, the difference in the incidence of PONV and hypotension is not significant (OR = 0.57; 95% CI: 0.18 to 178; OR = 0.90; 95% CI: 0.36 to 2.24). The incidence of PONV was higher in the ketamine group than the ondansetron group (OR = 4.49; 95% CI: 1.24 to 16.21). However, ketamine showed a lower incidence of hypotension compared to ondansetron (OR = 0.09; 95% CI: 0.00 to 3.23). Core temperature changes were reported graphically; there was no significant difference between ketamine and other pharmacological interventions.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSummary of findings and quality of evidence\u003c/em\u003e The Summary of findings with GRADE recommendations are shown in Table 2.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, we compared different randomized controlled trials to identify the beneficial aspects of ketamine. We compared the usage of ketamine and its relevance in anaesthetic shivering. In total, 16 studies including 1485 patients were analysed.\u003c/p\u003e\n\u003cp\u003eKetamine was first synthesized in the early 1960s as a safe alternative to phencyclidine\u003csup\u003e [26]\u003c/sup\u003e. It is a non-competitive -NMDA receptor antagonist with an effect of thermoregulation. Other than being a competitive NMDA receptor antagonist, ketamine also acts as an opioid agonist\u003csup\u003e [27]\u003c/sup\u003e. Further, it can cause blockage of amine uptake in the descending inhibitory monoaminergic pain pathways, having a local anaesthetic action and interacting with the muscarinic receptors\u003csup\u003e [28]\u003c/sup\u003e. In contrast, even at sub-anaesthetic doses, ketamine might cause a dissociative state, characterised by a sense of detachment from one’s physical body and the external world (depersonalization and derealization). Ketamine probably controls shivering by acting on non-shivering thermogenesis\u003csup\u003e [29]\u003c/sup\u003e. Ketamine is predominantly utilized as an anaesthetic agent that induces analgesia but for a long time it has been criticized for some of its side effects which include the induction of a psychedelic state causing agitation and hallucinations\u003csup\u003e [30]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe key findings of our analysis are as follows. Ketamine exposure was relatively better in reducing the occurrence of postanaesthetic shivering compared to placebo. Compared with tramadol and ondansetron, ketamine slightly lowered the incidence of postanaesthetic shivering although not significantly. The effect of ketamine on postanaesthetic shivering remained equally beneficial for both spinal and general types of anaesthesia. A dose of 0.5 mg/kg had an advance effect compared to 0.25 mg/kg on the postanaesthetic shivering rate. The effect remained constant for all types of surgical procedures including orthopaedic surgery, laparotomy, caesarean section, urological, ENT, and endoscopic surgeries. Compared to ketamine, pethidine showed a quicker responsive rate. However, sufficient data was not available in other studies to show any advantage of other pharmacological interventions.\u003c/p\u003e\n\u003cp\u003eFurthermore, we evaluated the side effects of the anaesthetic drugs and the role of ketamine in preventing or overcoming the effects. Moreover, the efficacy of ketamine was compared with a placebo. The side effects observed in the trials were nausea, vomiting, hypotension, bradycardia, and hallucinations. Ketamine showed a favourable outcome in reducing the incidence rate of hypotension and bradycardia as ketamine causes dose dependent direct stimulation of the CNS which leads to increased sympathetic nervous system stimulation followed by increased systemic blood pressure and heart rate.\u003c/p\u003e\n\u003cp\u003eHowever, there was no effect of ketamine in decreasing the incidence rate of nausea and vomiting as compared to placebo. As ketamine is known to have a hallucinogenic effect, it is considered to have a potential role in glutamatergic signalling in psychosis; therefore, the usage of ketamine is suggested to be associated with auditory and verbal hallucinations. In our comparative study, we also found that the rate of occurrence of hallucination episodes was much higher in patients receiving a ketamine dose of 0.5 mg/kg compared to a lower dose of 0.25 mg/kg. The hallucinogenic effect of ketamine was evident when compared with the placebo drugs, for which there was no incidence of hallucinations reported in any of the trials. Ketamine can cause sedation in postoperative patients and deep sedation is considered to be a severe adverse event. However, for those experiencing shivering, mild sedation may prevent them from hurting themselves. In our study, we paid special attention to the sedation score of patients, although pooled analysis was not conducted because of various sedation scales. We found that mild to moderate sedation was more commonly seen in patients receiving different doses of ketamine.\u003c/p\u003e\n\u003cp\u003eBesides various pharmacological interventions above, we noticed that active warming for elective caesarean delivery reduced the incidence of postoperative shivering and provided more stable perioperative temperature change \u003csup\u003e[31]\u003c/sup\u003e. Accumulating evidence has shown that the active warming method including electric heating, water-circulating garments, forced-air, and radiant heating is effective in preventing post-anaesthetic shivering. The current American Society of Anesthesiologists Task Force on Postanesthetic Care guidelines recommend forced-air warming as a common method to reduce shivering in the perioperative setting \u003csup\u003e[32]\u003c/sup\u003e. Future research should focus on combinations of pharmacological interventions with non-pharmacological methods to better solve this problem.\u003c/p\u003e\n\u003cp\u003eThe major limitation of our study is that we could not study the hemodynamical changes related to ketamine usage as there were no standard criteria being followed by the trials causing irrelevancy and uneven data for comparing and evaluating precise outcomes in this regard. Second, the sample size of included trials was relatively small which may decrease generalisability of our conclusions. Third, the evidence level for our outcomes was low or very low. However, we believe that our study is of value because it provided clear evidence of the benefit of prophylactic ketamine intervention for preventing post-anaesthetic shivering which may be helpful in clinical practice.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this meta-analysis, we assessed various aspects of ketamine usage in controlling post-anaesthetic shivering. We found that ketamine reduced the incidence rate of shivering compared to the placebo. Although it is beneficial, it did not show any superiority over other pharmacological interventions. Ketamine is of clinical value, but further studies should be performed on a wider scale to determine more emphasized results. Furthermore, larger clinical trials investigating the combination of different anti-shivering regimens are warranted.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eECG: electrocardiography; \u003ca href=\"javascript:;\"\u003eENT\u003c/a\u003e: \u003ca href=\"javascript:;\"\u003eear-nose-throat\u003c/a\u003e; NMDA: N-methy-D-aspartate; PONV: postoperative nausea and vomiting; PRISMA: Reporting Items for Systematic Reviews and Meta-Analysis; SpO2: oxygen saturation; CNS: central nervous system\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate:\u003c/em\u003e Not applicable\u003c/p\u003e\u003cp\u003e\u003cem\u003eConsent for publication:\u003c/em\u003e Not applicable\u003c/p\u003e\u003cp\u003e\u003cem\u003eAvailability of data and materials:\u003c/em\u003e The datasets used in the analysis was collected by online search, and the datasets analyzed in the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests:\u003c/em\u003e The authors declare that they have no competing interests.\u003c/p\u003e\u003cp\u003e\u003cem\u003eFunding:\u003c/em\u003e Support by the National Natural Science Foundation of China Grant Nos. 81070888 and 81230025 (to J-LC), the Scientific Innovation Group of\u003c/p\u003e\n\u003cp\u003e“Qing Lan Project” of Jiangsu Province (to J-LC), the Jiangsu Provincial\u003c/p\u003e\n\u003cp\u003eSpecial Program of Medical Science Grant No. BL2014029 (to J-LC); the Priority Academic Program Development of Jiangsu Higher Education Institutions (to J-LC).\u003c/p\u003e\u003cp\u003e\u003cem\u003eAuthors’ contributions:\u003c/em\u003e Study design: J. L. C., Y. H., Y. Z., A.M Writing of the manuscript: J. L. C., Y. H., Y. Z., A.M.\u003c/p\u003e\n\u003cp\u003eData analysis: Y. Z., M. A.\u003c/p\u003e\u003cp\u003e\u003cem\u003eAcknowledgements:\u003c/em\u003e Not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003eInsler SR, Sessler DI. Perioperative thermoregulation and temperature monitoring. Anesthesiology clinics 2006; 24: 823–37\u003c/li\u003e\u003cli\u003eAlfonsi P. Postanaesthetic Shivering. Drugs 2001; 61: 2193–205\u003c/li\u003e\u003cli\u003eHorn EP, Schroeder F, Wilhelm S, et al. Postoperative pain facilitates nonthermoregulatory tremor. Anesthesiology 1999; 91: 979–84\u003c/li\u003e\u003cli\u003eLenhardt R. The effect of anesthesia on body temperature control[J]. Front Biosci, 2010, 2:1145–1154.\u003c/li\u003e\u003cli\u003eMoeen SM, Moeen AM. Intrathecal dexamethasone vs. meperidine for prevention of shivering during transurethral prostatectomy: a randomized controlled trial. Acta anaesthesiologica Scandinavica 2017; 61: 749–57\u003c/li\u003e\u003cli\u003eLyons B, Carroll M, McDonald NJ. The treatment of postanaesthetic shivering: a double blind comparison between alfentanil and pethidine. Acta anaesthesiologica Scandinavica 1995; 39: 979–82\u003c/li\u003e\u003cli\u003eSachidananda R, Basavaraj K, Shaikh SI, Umesh G, Bhat T, Arpitha B. Comparison of Prophylactic Intravenous Magnesium Sulfate with Tramadol for Postspinal Shivering in Elective Cesarean Section: A Placebo Controlled Randomized Double-blind Pilot Study. Anesthesia, essays and researches 2018; 12: 130–4\u003c/li\u003e\u003cli\u003eNallam SR, Cherukuru K, Sateesh G. Efficacy of Intravenous Ondansetron for Prevention of Postspinal Shivering during Lower Segment Cesarean Section: A Double-Blinded Randomized Trial. Anesthesia, essays and researches 2017; 11: 508–13\u003c/li\u003e\u003cli\u003eBock M, Bauer M, Rosler L, Sinner B, Motsch J. Dolasetron and shivering. A prospective randomized placebo-controlled pharmaco-economic evaluation. Der Anaesthesist 2007; 56: 63–6, 8–70\u003c/li\u003e\u003cli\u003eAbdelhalim AA, Harethy SA, Alarfaj AM. Use of Ondansetron, Ketamine or Their Combination for Prevention of Post-Anesthetic Shivering. Journal of Alexandria Society Anesthesia and Intensive; 2014; 12: 121–70\u003c/li\u003e\u003cli\u003eAkram M, Raza H, Imam SM, Akram M, Raza H, Imam SM. Efficacy of prophylactic low dose ketamine and tramadol for prevention of shivering during spinal anaesthesia in patients undergoing lower abdominal surgeries. Pakistan Journal of Medical \u0026amp; Health Sciences 2017; 11: 378–80\u003c/li\u003e\u003cli\u003eAyatollahi V, Hajiesmaeili MR, Behdad S, Gholipur M, Abbasi HR. Comparison of prophylactic use of meperidine and two low doses of ketamine for prevention of post-anesthetic shivering: A randomized double-blind placebo controlled trial. Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences 2011; 16: 1340–6\u003c/li\u003e\u003cli\u003eHasannasab B, Banihashem N, Khoshbakht A. Prophylactic Effects of Doxapram, Ketamine and Meperidine in Postoperative Shivering. Anesthesiology and pain medicine 2016; 6: e27515\u003c/li\u003e\u003cli\u003eHonarmand A, Safavi MR. Comparison of prophylactic use of midazolam, ketamine, and ketamine plus midazolam for prevention of shivering during regional anaesthesia:a randomized double-blind placebo controlled trial. British journal of anaesthesia 2008; 101: 557–62\u003c/li\u003e\u003cli\u003eLakhe G, Adhikari KM, Khatri K, Maharjan A, Bajracharya A, Khanal H. Prevention of Shivering during Spinal Anesthesia: Comparison between Tramadol, Ketamine and Ondansetron. JNMA; journal of the Nepal Medical Association 2017; 56: 395–400\u003c/li\u003e\u003cli\u003eLema GF, Gebremedhn EG, Gebregzi AH, Desta YT, Kassa AA. Efficacy of intravenous tramadol and low-dose ketamine in the prevention of post-spinal anesthesia shivering following cesarean section: a double-blinded, randomized control trial. International journal of women’s health 2017; 9: 681–8\u003c/li\u003e\u003cli\u003eMohtadi AR, Goushe SMR, Ghomeishi A, Arbabi N. COMPARISON OF PREVENTIVE EFFECT OF LOW DOSE KETAMINE AND ONDANSETRON IN THE PREVENTION OF SHIVERING AFTER SPINAL ANESTHESIA IN PATIENTS UNDERGOING ELECTIVE CESAREAN SECTION. World Journal of Pharmacy and Pharmaceutical Sciences 2016; 5: 173–184\u003c/li\u003e\u003cli\u003eNorouzi M, Doroodian MR, Salajegheh S. Optimum dose of ketamine for prevention of postanesthetic shivering; a randomized double-blind placebo-controlled clinical trial. Acta anaesthesiologica Belgica 2011; 62: 33–6\u003c/li\u003e\u003cli\u003ePetskul S, Kitsiripant C, Rujirojindakul P, Chantarokorn A, Jullabunyasit A, Thinchana S. Prophylactic Low-Dose Ketamine to Prevent Post Anesthetic Shivering in Orthopedic Surgery: A Randomized-Controlled Study. Journal of the Medical Association of Thailand = Chotmaihet thangphaet 2016; 99: 400–5\u003c/li\u003e\u003cli\u003eSagir O, Gulhas N, Toprak H, Yucel A, Begec Z, Ersoy O. Control of shivering during regional anaesthesia: prophylactic ketamine and granisetron. Acta anaesthesiologica Scandinavica 2007; 51: 44–9\u003c/li\u003e\u003cli\u003eShakya S, Chaturvedi A, Sah BP. Prophylactic low dose ketamine and ondansetron for prevention of shivering during spinal anaesthesia. Journal of anaesthesiology, clinical pharmacology 2010; 26: 465–9\u003c/li\u003e\u003cli\u003eWason R, Jain N, Gupta P, Gogia AR. Randomized double-blind comparison of prophylactic ketamine, clonidine and tramadol for the control of shivering under neuraxial anaesthesia. Indian journal of anaesthesia 2012; 56: 370–5\u003c/li\u003e\u003cli\u003eZahra FA, Abudallah HM, Shabana RI, Abdulmageed WM, Abdulrazik SI, Nassar AM. Intramuscular ketamine for prevention of postanesthesia shivering in children. Saudi medical journal 2008; 29: 1255–9\u003c/li\u003e\u003cli\u003eZavareh SMHT, Morovati L, Koushki AM. A comparative study on the prophylactic effects of ketamine, dexamethasone, and pethidine in preventing postoperative shivering. Journal of Research in Medical Sciences 2012; 17: S175-S81\u003c/li\u003e\u003cli\u003eHan DY, Jeong HJ, Lee C, Choi DH. The Efficacy of Epidural Ketamine on Shivering during Transurethral Resection of the Prostate under Epidural Anesthesia. International neurourology journal 2010; 14: 105–11\u003c/li\u003e\u003cli\u003eNiesters M, Martini C, Dahan A. Ketamine for chronic pain: risks and benefits. British Journal of Clinical Pharmacology 2014; 77(2):357–67\u003c/li\u003e\u003cli\u003eDar A M, Qazi S M, Sidiq S. A placebo-controlled comparison of ketamine with pethidine for the prevention of postoperative shivering. Southern African Journal of Anaesthesia \u0026amp; Analgesia 2013; 18:340–343\u003c/li\u003e\u003cli\u003eAroni F, Iacovidou N, Dontas I, et al. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug[J]. Journal of Clinical Pharmacology, 2013, 49(8):957–964.\u003c/li\u003e\u003cli\u003eSharma DR, Thakur JR. Ketamine and shivering. Anaesthesia 2010; 45: 252–3\u003c/li\u003e\u003cli\u003eDe Witte J, Sessler DI. Perioperative shivering: physiology and pharmacology. Anesthesiology 2002; 96:467–84\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 16.15pt;\"\u003e\n\u003ctd style=\"width: 461.25pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.15pt;\" colspan=\"7\" width=\"615\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 16.0pt; font-family: 'Arial',sans-serif;\"\u003eTable1.Summary of Characteristics of Included Studies\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16.15pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.15pt;\" rowspan=\"2\" width=\"79\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eStudy ID\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.15pt;\" rowspan=\"2\" width=\"77\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eParticipants\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.15pt;\" rowspan=\"2\" width=\"71\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eSurgery Types\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.15pt;\" rowspan=\"2\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eAnesthesia Methods\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 150.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt; height: 16.15pt;\" colspan=\"2\" width=\"201\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eComparison\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 16.15pt;\" rowspan=\"2\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eNon-pharmacological Warming Methods\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 43.95pt;\"\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 43.95pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eControl Group\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 43.95pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eIntervention Group\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 72.75pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 72.75pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSagir\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2007\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 72.75pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e160 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-65yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 72.75pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eurological surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 72.75pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 72.75pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(40): saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 72.75pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(40):ketamine 0.5mg/kg iv;G(40):granisetron 3mg,iv;KG(40)ketamine 0.25/kg+granisetron 1.5mg iv\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 72.75pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eAll patients were covered with drapes and a cotton blanket .Fluids were preheated to 37\u003csup\u003eo\u003c/sup\u003ec\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 57.9pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.9pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eHonarmand\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2008\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.9pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e120 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-60yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.9pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eorthopaedic surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.9pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.9pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(30) saline iv; K(30) ketamine 0.5mg/kg iv; \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.9pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eM(30) midazolam 75\u0026micro;g/kg iv; KM(30) ketamine 0. 25mg/kg+midazolam 37.5\u0026micro;g/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.9pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eFluids were preheated to 37\u003csup\u003eo\u003c/sup\u003ec\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 63.65pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.65pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eZahra\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2008\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.65pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e120 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e5-12yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.65pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003etonsillectomy surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.65pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eGA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.65pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(40):saline\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.65pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(40):ketamine 1mg/kg;P(40):pethidine 0.5mg/kg\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.65pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNone.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 83.7pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 83.7pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eHan\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2010\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 83.7pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e93 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e51-78yr\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 83.7pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003etransurethral resection of the prostate\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 83.7pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 83.7pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(31): epidural 0.75% ropivacaine\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 83.7pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK1(32): epdural ketamine 0.2mg/kg+0.75%ropivacaine; K2(30): epidural ketamine 0.4mg/kg+0.75%ropivacaine\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 83.7pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 70.75pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 70.75pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eShakya\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2010\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 70.75pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e120 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 70.75pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eLower abdominal surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 70.75pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 70.75pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(40):saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 70.75pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(40): ketamine\u0026nbsp; 0.25mg/kg iv;O(40):ondansetron 4mg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 70.75pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ePatients were covered with standard single blanket\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eAyatollahi\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2011\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e120 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e20-50yr \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eendoscopic sinus surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eGA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(30): saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK1(30): 0.3mg/kg iv; K2(30) : 0.5mg/kg iv; M(30): meperidine 0.4mg/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ePatients were covered with a cotton blanket\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 1.9pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNorouzi\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2011\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e120 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-65yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eelective orthopedic surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eGA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(30):saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK1(30):ketamine 0.125mg/kg iv;K2(30):ketamine 0.25mg/kg iv;K3(30):ketamine 0.5mg/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 49.15pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 49.15pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eWason\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2012\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 49.15pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e200 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-65yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 49.15pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eower abdominal or lower limb surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 49.15pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 49.15pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(50):saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 49.15pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(50):ketamine 0.5mg/kg iv;C(50):clonidine 75mcg;T(50):tramadol 0.5mg/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 49.15pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eFluids were preheated to 37\u003csup\u003eo\u003c/sup\u003ec\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 58.9pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eZavareh\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2012\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e135 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-70yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eelective surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eGA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(45):ketamine 0.5mg/kg iv;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eP(45):pethidine 0.5mg/kg;D(45):dexamethasone,0.6mg/kg\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 63.3pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.3pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eAbdelhalim\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2014\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.3pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e120 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-45yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.3pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eENT surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.3pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eGA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.3pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(30): saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.3pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eO(30): ondansetron 8mg iv; K(30): ketamine 0.5mg/kg iv; OK(30)ondansetron 8mg+ketamine 0.25mg/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 63.3pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 57.65pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.65pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ePetskul\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2016\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.65pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e183 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-65yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.65pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eorthopedic surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.65pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eGA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.65pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(92):saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.65pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(91):ketamine 0.25mg/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 57.65pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eAll patients were warmed by air force warmer\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 92.7pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 92.7pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eMohtadi\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2016\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 92.7pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e117 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-40yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 92.7pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ecesarean section\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 92.7pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 92.7pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(39):saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 92.7pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(39):ketamine 0.25mg/kg,iv;O(39):ondansetron 4mg,iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 92.7pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNone\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 77.75pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 77.75pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eHasannasab 2016\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 77.75pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e120 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e20-45yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 77.75pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003egynecologic surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 77.75pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eGA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 77.75pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(40): ketamine 0.25mg/kg iv; \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 77.75pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eM(40): meperidine 20mg iv ; D(40): doxapram 0.25mg/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 77.75pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ePatients were covered with a standard blanket\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 76.7pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 76.7pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eLakhe\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2017\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 76.7pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e120 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-65 years\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 76.7pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003egynecological and orthopedic surgery\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 76.7pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 76.7pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(30):saline,iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 76.7pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eT(30):tramadol 0.5mg/kg iv O(30):ondansetron 4mg,iv;K(30):ketamine 0.25mg/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 76.7pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ePatients were covered with drapes\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 1.9pt;\"\u003e\n\u003ctd style=\"width: 58.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"79\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eLema\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2017\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 57.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"77\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e123 patients\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e18-39yr\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 53.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"71\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ecesarean section\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.25pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"67\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSA\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 69.0pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"92\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eC(41):saline iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 81.75pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"109\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eK(41):ketamine 0.2mg/kg iv;T(41): tramadol 0.5mg/kg iv\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 90.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 1.9pt;\" width=\"121\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ePatients were covered with drapes\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cspan style=\"font-family: Arial, sans-serif;\"\u003eAbbreviations: yr, years; GA, general anesthesia; SA, spinal anesthesia; C, control;O, ondansetron; T, t\u003c/span\u003e\u003cspan style=\"font-family: 'Arial',sans-serif;\"\u003eramadol; M, meperidine; D, doxapram; G, granisetron; CL, clonidine; P, pethidine.\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: 12.0pt; line-height: 150%;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: 12.0pt; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"margin-bottom: 12.0pt; line-height: 150%;\"\u003e\u003cspan style=\"line-height: 150%;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cspan style=\"font-size: 5.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 5.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u0026nbsp;\u003c/p\u003e\n\n\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 419.8pt; border-top: solid black 1.5pt; border-left: none; border-bottom: solid black 1.5pt; border-right: none; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"7\" width=\"560\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 9.0pt; font-family: 'Arial',sans-serif;\"\u003eTable 2. Summary of findings with GRADE recommendations.\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 419.8pt; border: none; border-bottom: solid black 1.5pt; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"7\" width=\"560\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 9.0pt; font-family: 'Arial',sans-serif;\"\u003eketamine for postoperative shivering\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 419.8pt; border: none; border-bottom: solid black 1.5pt; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"7\" width=\"560\"\u003e\n\u003cp style=\"margin-bottom: 12.0pt;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003ePatient or population:\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e patients with postoperative shivering\u003cbr /\u003e\u003cstrong\u003eSettings:\u003c/strong\u003e hospitals\u003cbr /\u003e\u003cstrong\u003eIntervention:\u003c/strong\u003e ketamine\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 72.95pt; border: none; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"2\" width=\"97\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eOutcomes\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 125.65pt; border: none; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eIllustrative comparative risks* (95% CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46.2pt; border: none; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"2\" width=\"62\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eRelative effect\u003cbr /\u003e(95% CI)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.7pt; border: none; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"2\" width=\"85\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eNo of Participants\u003cbr /\u003e(studies)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 60.85pt; border: none; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"2\" width=\"81\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eQuality of the evidence\u003cbr /\u003e(GRADE)\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.45pt; border: none; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"2\" width=\"67\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eComments\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eAssumed risk\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eCorresponding risk\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 72.95pt; border: none; border-bottom: solid black 1.5pt; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" width=\"97\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.5pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eControl\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.5pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eKetamine\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46.2pt; border: none; border-bottom: solid black 1.5pt; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" width=\"62\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.7pt; border: none; border-bottom: solid black 1.5pt; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" width=\"85\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 10.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 60.85pt; border: none; border-bottom: solid black 1.5pt; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" width=\"81\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 10.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.45pt; border: none; border-bottom: solid black 1.5pt; background: steelblue; padding: .75pt .75pt .75pt .75pt;\" width=\"67\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 10.0pt; font-family: 'Times New Roman',serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 72.95pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"97\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eIncidence of shivering\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eStudy population\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46.2pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"62\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eOR 0.13 \u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e(0.06 to 0.26)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.7pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"85\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e1166\u003cbr /\u003e(13 studies)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 60.85pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"81\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Microsoft YaHei',sans-serif;\"\u003e\u0026oplus;\u0026oplus;\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Cambria Math',serif;\"\u003e⊝⊝\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e\u003cstrong\u003elow\u003c/strong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.45pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"67\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e468 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e103 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(50 to 186)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eModerate\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e500 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e115 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(57 to 206)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 72.95pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"97\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eNausea and vomitting\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eStudy population\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46.2pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"62\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eOR 0.7 \u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e(0.44 to 1.12)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.7pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"85\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e986\u003cbr /\u003e(11 studies)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 60.85pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"81\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Microsoft YaHei',sans-serif;\"\u003e\u0026oplus;\u0026oplus;\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Cambria Math',serif;\"\u003e⊝⊝\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e\u003cstrong\u003elow\u003c/strong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.45pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"67\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e123 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e89 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(58 to 136)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eModerate\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e125 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e91 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(59 to 138)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 72.95pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"97\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eHypotension\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eStudy population\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46.2pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"62\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eOR 0.3 \u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e(0.18 to 0.49)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.7pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"85\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e573\u003cbr /\u003e(7 studies)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 60.85pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"81\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Microsoft YaHei',sans-serif;\"\u003e\u0026oplus;\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Cambria Math',serif;\"\u003e⊝⊝⊝\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e\u003cstrong\u003every low\u003c/strong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.45pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"67\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e225 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e80 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(50 to 125)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eModerate\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e200 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e70 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(43 to 109)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 72.95pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"97\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eBradycardia\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eStudy population\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46.2pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"62\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eOR 0.14 \u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e(0.04 to 0.52)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.7pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"85\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e193\u003cbr /\u003e(2 studies)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 60.85pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"81\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Microsoft YaHei',sans-serif;\"\u003e\u0026oplus;\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Cambria Math',serif;\"\u003e⊝⊝⊝\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e\u003cstrong\u003every low\u003c/strong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.45pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"67\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e136 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e22 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(6 to 76)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eModerate\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e165 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e27 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(8 to 93)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 72.95pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"97\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eHallucination\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eStudy population\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 46.2pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"62\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eOR 4.41 \u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e(1.14 to 17.07)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 63.7pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"85\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e423\u003cbr /\u003e(5 studies)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 60.85pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"81\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Microsoft YaHei',sans-serif;\"\u003e\u0026oplus;\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Cambria Math',serif;\"\u003e⊝⊝⊝\u003c/span\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u003cbr /\u003e\u003cstrong\u003every low\u003c/strong\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 50.45pt; border: none; border-bottom: solid black 1.0pt; padding: .75pt .75pt .75pt .75pt;\" rowspan=\"4\" width=\"67\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e0 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e0 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(0 to 0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 125.65pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: 2.25pt 2.25pt 2.25pt 2.25pt;\" colspan=\"2\" width=\"168\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003eModerate\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 50.7pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"68\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e0 per 1000\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 74.95pt; border: none; border-bottom: solid black 1.0pt; background: lightgrey; padding: .75pt .75pt .75pt .75pt;\" width=\"100\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e0 per 1000\u003c/span\u003e\u003c/strong\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif; color: black;\"\u003e\u003cbr /\u003e(0 to 0)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 419.8pt; border: none; border-bottom: solid black 1.5pt; padding: .75pt .75pt .75pt .75pt;\" colspan=\"7\" width=\"560\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003e*The basis for the \u003cstrong\u003eassumed risk\u003c/strong\u003e (e.g. the median control group risk across studies) is provided in footnotes. The \u003cstrong\u003ecorresponding risk\u003c/strong\u003e (and its 95% confidence interval) is based on the assumed risk in the comparison group and the \u003cstrong\u003erelative effect\u003c/strong\u003e of the intervention (and its 95% CI).\u003cbr /\u003e\u003cstrong\u003eCI:\u003c/strong\u003e Confidence interval; \u003cstrong\u003eOR:\u003c/strong\u003e Odds ratio; \u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 419.8pt; border: none; border-bottom: solid black 1.5pt; padding: .75pt .75pt .75pt .75pt;\" colspan=\"7\" width=\"560\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 8.0pt; font-family: 'Arial',sans-serif;\"\u003eGRADE Working Group grades of evidence\u003cbr /\u003e\u003cstrong\u003eHigh quality:\u003c/strong\u003e Further research is very unlikely to change our confidence in the estimate of effect. \u003cbr /\u003e\u003cstrong\u003eModerate quality:\u003c/strong\u003e Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.\u003cbr /\u003e\u003cstrong\u003eLow quality:\u003c/strong\u003e Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.\u003cbr /\u003e\u003cstrong\u003eVery low quality:\u003c/strong\u003e We are very uncertain about the estimate.\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\n\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 430.2pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"5\" width=\"574\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eTable 3. Comparisons of incidence of other side effects\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 82.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eSide effccts\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"114\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNumber of studies\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 87.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"116\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eKetamine\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 62.8pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ePlacebo\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 111.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"149\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 82.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"114\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 87.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"116\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eEvents/Total\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 62.8pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eEvents/Total\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 111.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"149\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eOdds Ratio (95% CI)\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 82.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNausea\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eand vomitting\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"114\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e11\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 87.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"116\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e48/523\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 62.8pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e57/463\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 111.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"149\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0.70 [0.44, 1.12]\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 82.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eHypotension\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"114\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e6\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 87.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"116\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e23/302\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 62.8pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e61/271\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 111.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"149\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0.30 [0.18, 0.49]\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 82.9pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eBradycardia\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.7pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"114\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 87.3pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"116\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e3/112\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 62.8pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e11/81\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 111.5pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"149\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0.14 [0.04, 0.52]\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 82.9pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"111\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eHallucination\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 85.7pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"114\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e5\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 87.3pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"116\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e16/272\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 62.8pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"84\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0/151\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 111.5pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"149\"\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e4.41 [1.14, 17.07]\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp style=\"text-align: left; line-height: 150%;\"\u003e\u003cspan style=\"font-size: 12.0pt; line-height: 150%; font-family: 'Arial',sans-serif;\"\u003eAbbreviations: CI, confidence interval.\u003c/span\u003e\u003c/p\u003e\n\n\n\u003ctable style=\"border-collapse: collapse; border: none;\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 426.1pt; border-top: solid windowtext 1.0pt; border-left: none; border-bottom: solid windowtext 1.0pt; border-right: none; padding: 0in 5.4pt 0in 5.4pt;\" colspan=\"4\" width=\"568\"\u003e\n\u003cp style=\"text-align: left; line-height: 150%;\"\u003e\u003cstrong\u003e\u003cspan style=\"font-size: 10.0pt; line-height: 150%; font-family: 'Arial',sans-serif;\"\u003eTable 4. Episodes of hallucination based on the dose of ketamine. \u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 103.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"139\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eStudy ID\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eDose of ketamine\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 133.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"178\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eKetamine\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.2pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003ePlacebo\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 103.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"139\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 133.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"178\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eEvents/Total\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.2pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eEvents/Total\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 41.6pt;\"\u003e\n\u003ctd style=\"width: 103.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 41.6pt;\" width=\"139\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eHonarmand\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2008\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 41.6pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0.5mg/kg\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 133.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 41.6pt;\" width=\"178\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e3/30\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.2pt; border: none; padding: 0in 5.4pt 0in 5.4pt; height: 41.6pt;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0/30\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 103.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"139\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eHan\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2010\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0.4mg/kg\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 133.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"178\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2/30\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.2pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0/31\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 103.95pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"139\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNorouzi\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2011\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.55pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0.25mg/kg\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 133.4pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"178\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e1/30\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 76.2pt; border: none; padding: 0in 5.4pt 0in 5.4pt;\" width=\"102\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e0/30\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd style=\"width: 103.95pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"139\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eNorouzi\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2011\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eAyatollahi\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2011\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003eAbdelhalim\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e2014\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; font-family: 'Arial',sans-serif;\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"width: 112.55pt; border: none; border-bottom: solid windowtext 1.0pt; padding: 0in 5.4pt 0in 5.4pt;\" width=\"150\"\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cspan style=\"font-size: 12.0pt; 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Due to the lack of high-quality evidence, it is difficult to draw a conclusion about optimal anti-shivering medication. The main purpose of this meta-analysis was to analyze and evaluate the efficacy and safety of prophylactic use of ketamine for preventing postanesthetic shivering. \u003c/p\u003e\u003cp\u003eMethods \u003c/p\u003e\u003cp\u003eWe used a systematic approach, also known as meta-analysis, to further address postoperative shivering. We searched the following databases: Medline, Embase, and the Cochrane Central Register of Controlled Trails for randomized controlled trials. The primary outcome observed was the difference of the incidence rate of postanesthetic shivering\u0026nbsp;between ketamine group and placebo group .\u0026nbsp;The secondary outcomes were the sedation score and incidence of the side effects caused by ketamine and any other drugs\u0026nbsp;utilized in the studies. \u003c/p\u003e\u003cp\u003eResults \u003c/p\u003e\u003cp\u003eIn this meta-analysis, we analyzed a total of 16 trials including 1485 patients. Ketamine reduced the incidence rate of postanesthetic shivering compared to a placebo (odds ratio [OR]: 0.13, 95% confidence interval [CI]: 0.06 to 0.26, P＜0.01). Regarding side effects, there was no evident variability of the incidence of nausea and vomiting. Usage of ketamine was associated with a lower rate of hypotension and bradycardia when compared to a placebo. Hallucinations were more frequently observed in patients who received higher doses of ketamine. No significant difference was found in the incidence of postanesthetic shivering with ketamine versus other pharmacological interventions. \u003c/p\u003e\u003cp\u003eConclusions \u003c/p\u003e\u003cp\u003eKetamine can prevent postanesthetic shivering without severe side effects. However, ketamine shows no advantage over other anti-shivering drugs.\u003c/p\u003e","manuscriptTitle":"Efficacy and safety of prophylactic use of ketamine for prevention of postanesthetic shivering: A system review and meta analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":3,"date":"2019-11-19 13:35:47","doi":"10.21203/rs.2.10245/v3","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2019-11-25T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-11-16T12:00:00+00:00","index":1,"fulltext":"Recommendation: Accept without revision\nForm responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n\nComments to Author:\n---\nDear authors,\n\nThank you for allowing me to read this work. I believe it is now suitable for publication.\n\n"},{"type":"editorAssigned","content":"","date":"2019-11-13T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewersInvited","content":"","date":"2019-11-13T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-11-13T12:00:00+00:00","index":1,"fulltext":""},{"type":"editorInvited","content":"","date":"2019-11-12T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-11-07T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}},{"code":2,"date":"2019-10-08 20:29:39","doi":"10.21203/rs.2.10245/v2","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Minor revision","date":"2019-10-30T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-10-23T12:00:00+00:00","index":5,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **Not relevant to this manuscript**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Does the work include the necessary controls?\nIf not, please specify which controls are required in your comments to the authors.\tYes: **Are the conclusions drawn adequately supported by the data shown?\nIf not, please explain in your comments to the authors.\tYes**\n"},{"type":"editorInvitedReview","content":"","date":"2019-10-23T12:00:00+00:00","index":3,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **Not relevant to this manuscript**\n* Quality of written English: **Needs some language corrections before being published**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Does the work include the necessary controls?\nIf not, please specify which controls are required in your comments to the authors.\tYes: **Are the conclusions drawn adequately supported by the data shown?\nIf not, please explain in your comments to the authors.\tYes**\n"},{"type":"reviewerAgreed","content":"","date":"2019-10-13T12:00:00+00:00","index":5,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-10-13T12:00:00+00:00","index":1,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Does the work include the necessary controls?\nIf not, please specify which controls are required in your comments to the authors.\tYes: **Are the conclusions drawn adequately supported by the data shown?\nIf not, please explain in your comments to the authors.\tYes**\n"},{"type":"editorInvitedReview","content":"","date":"2019-10-13T12:00:00+00:00","index":2,"fulltext":"Form responses:\n---\n* Are the methods appropriate and well described?: **Yes**\n* Does the work include the necessary controls?: **Yes**\n* Are the conclusions drawn adequately supported by the data shown?: **Yes**\n* Are you able to assess any statistics in the manuscript or would you recommend an additional statistical review?: **I am able to assess the statistics**\n* Quality of written English: **Acceptable**\n* Declaration of competing interests: **I declare that I have no competing interests.**\n* Does the work include the necessary controls?\nIf not, please specify which controls are required in your comments to the authors.\tYes: **Are the conclusions drawn adequately supported by the data shown?\nIf not, please explain in your comments to the authors.\tYes**\n"},{"type":"reviewersInvited","content":"","date":"2019-10-09T12:00:00+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-10-09T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-10-09T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-10-09T12:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-10-09T12:00:00+00:00","index":4,"fulltext":""},{"type":"editorAssigned","content":"","date":"2019-10-08T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-10-07T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-10-07T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn 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authors.\tYes**\n"},{"type":"editorInvitedReview","content":"","date":"2019-07-16T12:00:00+00:00","index":2,"fulltext":"Form responses:\n---\n* Does the work include the necessary controls?\nIf not, please specify which controls are required in your comments to the authors.\tYes: **Are the conclusions drawn adequately supported by the data shown?\nIf not, please explain in your comments to the authors.\tYes**\n"},{"type":"editorInvitedReview","content":"","date":"2019-07-07T12:00:00+00:00","index":5,"fulltext":"Form responses:\n---\n* Does the work include the necessary controls?\nIf not, please specify which controls are required in your comments to the authors.\tUnable to assess: **Are the conclusions drawn adequately supported by the data shown?\nIf not, please explain in your comments to the authors.\tNo**\n"},{"type":"editorInvitedReview","content":"","date":"2019-07-01T12:00:00+00:00","index":4,"fulltext":"Form responses:\n---\n* Does the work include the necessary controls?\nIf not, please specify which controls are required in your comments to the authors.\tYes: **Are the conclusions drawn adequately supported by the data shown?\nIf not, please explain in your comments to the authors.\tYes**\n"},{"type":"reviewerAgreed","content":"","date":"2019-06-29T12:00:00+00:00","index":6,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-06-29T12:00:00+00:00","index":5,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-06-28T12:00:00+00:00","index":4,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2019-06-26T12:00:00+00:00","index":1,"fulltext":"Form responses:\n---\n* Does the work include the necessary controls?\nIf not, please specify which controls are required in your comments to the authors.\tUnable to assess: **Are the conclusions drawn adequately supported by the data shown?\nIf not, please explain in your comments to the authors.\tUnable to assess**\n"},{"type":"reviewerAgreed","content":"","date":"2019-06-26T12:00:00+00:00","index":3,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-06-26T12:00:00+00:00","index":2,"fulltext":""},{"type":"reviewerAgreed","content":"","date":"2019-06-17T12:00:00+00:00","index":1,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2019-06-16T12:00:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2019-06-10T12:00:00+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2019-06-10T12:00:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2019-06-10T12:00:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"","date":"2019-06-03T12:00:00+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a1d74979-42c8-4ad9-9366-ef96f92c6749","owner":[],"postedDate":"November 19th, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":37132,"name":"Anesthesiology \u0026 Pain Medicine"}],"tags":[],"updatedAt":"","versionOfRecord":{"articleIdentity":"rs-1284","link":"https://doi.org/10.1186/s12871-019-0910-8","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2019-12-30 12:00:00","publishedOnDateReadable":"December 30th, 2019"},"versionCreatedAt":"2019-11-19 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