Comparison of Preemptive Effect of Intravenous Ketorolac Versus Nalbuphine on Postoperative Shivering and Pain in Patients Undergoing Surgery Under Spinal Anesthesia: A Prospective, Randomized, Double-Blind Study.

BACKGROUND: Postoperative pain and postanesthesia shivering are the two common problems in patients undergoing surgery under spinal anesthesia (SA). The present study aimed to compare the preemptive prescription of the single dose of intravenous (IV) ketorolac versus nalbuphine on postoperative shivering and pain in patients undergoing surgery under SA. METHODS: Present study was a prospective, randomized double-blind study, conducted on patients of either gender, with American Society of Anesthesiologists physical status class I or II, aged 21-60 years, posted for elective lower abdominal surgeries under SA. Patients were randomized by computer-generated random numbers into two groups of 50 patients each: group N (received 0.2 mg/kg nalbuphine IV) and group K (received 0.5 mg/kg ketorolac IV). RESULTS: The incidence of postoperative shivering was 22 % and 36 % in groups N and K respectively and the difference was statistically significant. The first request for analgesia (minutes) was later in group N (295.17 ± 54.62) than in group K (223.80 ± 15.34) and the difference was statistically significant. Increased total analgesic consumption was noted more in group K (131.34 ± 43.27) than in group N (79.23 ± 21.34), and the difference was statistically significant (P < 0.0001). The incidence of side effects was comparable among both groups. CONCLUSION: Preemptive nalbuphine had less incidence of postoperative shivering, delayed first request for analgesia, and less total analgesic consumption than ketorolac in patients undergoing surgery under SA.

Postspinal anesthesia shivering in lower abdominal and lower limb surgeries: a randomized controlled comparison between paracetamol and dexamethasone.

BACKGROUND: Shivering is known to be a frequent complication in patients undergoing surgery under neuraxial anesthesia with incidence of 40-70%. Although many pharmacological agents have been used to treat or prevent postspinal anesthesia shivering (PSAS), the ideal treatment wasn't found. This study evaluated the efficacy of paracetamol and dexamethasone to prevent PSAS in patients undergoing lower abdominal and lower limb surgeries. METHODS: Three hundred patients scheduled for surgeries under spinal anesthesia (SA) were allocated into three equal groups to receive a single preoperative dose of oral paracetamol 1 g (P group), dexamethasone 8 mg intravenous infusion (IVI) in 100 ml normal saline (D group) or placebo (C group), 2 h preoperatively, in a randomized, double-blind trial. The primary endpoint was the incidence of clinically significant PSAS. Secondary endpoints included shivering score, the change in hemodynamics, adverse events (e.g., nausea, vomiting and pruritis) and patients` satisfaction. RESULTS: Clinically significant PSAS was recorded as (15%) in P group, (40%) in D group and (77%) in C group (P < 0.001). The mean blood pressure values obtained over a 5-25 min observation period were significantly higher in the D group (P < 0.001). Core temperature 90 min after SA was significantly lower in the 3 groups compared to prespinal values (P < 0.001). Nausea, vomiting and pruritis were significantly higher in the C group (P < 0.001). P and D groups were superior to C group regarding the patients' satisfaction score (P < 0.001). CONCLUSION: Paracetamol and dexamethasone were effective in prevention of PSAS in patients undergoing lower abdominal and lower limb surgeries compared to placebo controls. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03679065 / Registered 20 September 2018 - Retrospectively registered, http://www.ClinicalTrial.gov .

Independent and combined impact of hypoxia and acute inorganic nitrate ingestion on thermoregulatory responses to the cold.

PURPOSE: This study assessed the impact of normobaric hypoxia and acute nitrate ingestion on shivering thermogenesis, cutaneous vascular control, and thermometrics in response to cold stress. METHOD: Eleven male volunteers underwent passive cooling at 10 °C air temperature across four conditions: (1) normoxia with placebo ingestion, (2) hypoxia (0.130 FiO2) with placebo ingestion, (3) normoxia with 13 mmol nitrate ingestion, and (4) hypoxia with nitrate ingestion. Physiological metrics were assessed as a rate of change over 45 min to determine heat loss, and at the point of shivering onset to determine the thermogenic thermoeffector threshold. RESULT: Independently, hypoxia expedited shivering onset time (p = 0.05) due to a faster cooling rate as opposed to a change in central thermoeffector thresholds. Specifically, compared to normoxia, hypoxia increased skin blood flow (p = 0.02), leading to an increased core-cooling rate (p = 0.04) and delta change in rectal temperature (p = 0.03) over 45 min, yet the same rectal temperature at shivering onset (p = 0.9). Independently, nitrate ingestion delayed shivering onset time (p = 0.01), mediated by a change in central thermoeffector thresholds, independent of changes in peripheral heat exchange. Specifically, compared to placebo ingestion, no difference was observed in skin blood flow (p = 0.5), core-cooling rate (p = 0.5), or delta change in rectal temperature (p = 0.7) over 45 min, while nitrate reduced rectal temperature at shivering onset (p = 0.04). No interaction was observed between hypoxia and nitrate ingestion. CONCLUSION: These data improve our understanding of how hypoxia and nitric oxide modulate cold thermoregulation.

The effect of adding intrathecal magnesium sulphate to bupivacaine-fentanyl spinal anesthesia: A meta-analysis of randomized controlled trials.

TRIAL DESIGN: The current study is a meta-analysis designed to assess the effect of adding magnesium to a combination of intrathecal bupivacaine and fentanyl. METHODS: The protocol was registered in PROSPERO with the number CRD42020177618. PubMed, Cochrane library, Web of Science, and Google Scholar were searched for randomized controlled trials investigating the effect of adding magnesium to a combination of intrathecal bupivacaine and fentanyl. The continuous data were presented as Ratio of means (RoM). Risk ratio (RR) along with 95% confidence interval (CI) was utilized to assess the dichotomous data. RESULTS: Ten trials were involved in the present study with 720 adult patients. Compared with control, intrathecal magnesium prolonged time to the first analgesic requirement by an estimate of 1.23 (RoM: 1.23; 95%CI: 1.13-1.33; P < .00001), prolonged adequate sensory block duration for surgery by an estimate of 1.16 (RoM: 1.16; 95%CI: 1.05-1.27; P = .003), delayed time to maximum sensory level by an estimate of 1.38 (RoM: 1.38; 95%CI: 1.07-1.78; P = .01) and reduced the incidence of shivering following spinal anesthesia (risk ratio: 0.38; 95%CI: 0.18 to 0.81, P = .01) without influence on time to full motor recovery or incidences of hypotention, bradycardia, nausea, and vomiting or pruritis. CONCLUSION: Intrathecal magnesium, when added to a combination of intrathecal bupivacaine and fentany, prolongs the analgesic duration of spinal anesthesia without increased incidences of side effects.

Effects of oral premedication with tramadol, pregabalin or clonidine on shivering after spinal anaesthesia in patients undergoing hysteroscopic procedures.

BACKGROUND: Shivering is a common complication of neuraxial anaesthesia. We compared the efficacy of tramadol, clonidine and pregabalin in preventing post-spinal anaes-thesia shivering in hysteroscopic procedures. METHODS: A prospective, randomized, triple-blind, controlled clinical trial involving 120 ASA I-II women, aged 18-60 years. The patients were randomly allocated to receive either oral clonidine 0.2 mg (group C), tramadol 100 mg (group T), pregabalin 150 mg (group P) or placebo (group O) 90 minutes before spinal anaesthesia. The body tempe-rature was monitored at the forehead and tympanic membrane. The primary outcome was the occurrence of perioperative shivering. The secondary outcomes were the side effects and meperidine requirements to treat shivering. RESULTS: All groups had comparable demographic data. Group C showed the lowest incidence, severity and number of intraoperative and postoperative shivering attacks. The time to the first shivering attack was significantly longer in group C than the other groups and in group T than groups P and O. The severity of shivering attacks was comparable among groups C, T and P while being significantly lower than group O. Meperidine requirements were significantly lower in group C. Groups C, T and P had a significantly higher sedation score than group O. The incidences of dizziness, nausea and vomiting were highest in group T. CONCLUSIONS: Tramadol, pregabalin and clonidine seem to be effective oral premedications to reduce the incidence, frequency and severity of post-spinal shivering but clonidine proved to be more effective and tolerable.

Effect of intrathecal lipophilic opioids on the incidence of shivering in women undergoing cesarean delivery after spinal anesthesia: a systematic review and bayesian network meta- analysis of randomized controlled trials.

BACKGROUND: Shivering is a common side effect in women having cesarean delivery (CD) under spinal anesthesia, which can be bothersome to the patient, and it can also interfere with perioperative monitoring. In several studies, the intrathecal (IT) addition of a lipophilic opioid to local anesthetics has been shown to decrease the incidence of shivering. OBJECTIVE: We performed this network meta-analysis to evaluate the effects of intrathecal lipophilic opioids in preventing the incidence of shivering in patients undergoing CD. METHODS: This review was planned according to the PRISMA for Network Meta-Analysis (PRISMA-NMA) guidelines. An English literature search of multiple electronic databases was conducted. We included randomized controlled trials (RCTs) that reported on the incidence of shivering, with study groups receiving either IT fentanyl, sufentanil, or meperidine in women undergoing CD under spinal anesthesia. Quality of the studies was assessed using the modified Oxford scoring system. Using random-effects modeling, dichotomous data were extracted and summarized using odds ratio (OR) with a 95% credible interval (CrI). Statistical analysis was conducted using R studio version 1.0.153 - Inc. RESULTS: Twenty-one studies consisting of 1433 patients (Control group: 590 patients in twenty-one studies; Fentanyl group:199 patients in seven studies; Sufentanil group: 156 patients in five studies; Meperidine group: 488 patients in ten studies) met the inclusion criteria for this systematic review investigating the effect of intrathecal lipophilic opioids in preventing the incidence of shivering in women undergoing cesarean delivery under spinal anesthesia. Methodological validity scores ranged from 3 to 7. The Bayesian mixed network estimate showed the incidence of shivering was significantly lower with IT fentanyl (pooled odds ratio (OR): 0.13; 95% credible interval (CrI): 0.04 to 0.35; P = 0.0004) and IT meperidine (OR: 0.12; 95% CrI: 0.05 to 0.29; P < 0.00001), but not with IT sufentanil (OR: 0.37; 95% CrI: 0.11 to 1.22; P = 0.23). The IT fentanyl group had a significantly lower incidence of intraoperative discomfort [Risk Ratio (RR): 0.19; 95% CI: 0.10-0.35; P < 0.00001], the IT sufentanil group had a significantly higher incidence of pruritus (RR: 6.18; 95% CI: 1.18-32.46; P = 0.03) The IT meperidine group had a significantly lower incidence of intraoperative discomfort (2.7% vs. 13.6%; RR: 0.22; 95% CI: 0.09-0.55; P = 0.001), but there was a significant increase in nausea and vomiting (IT meperidine group vs. Control group: 42.7% vs. 19.4%; RR: 2.56; 95% CI: 1.14-5.75; P = 0.02). Meta-regression analysis based on the opioid dose and quality of the study did not impact the final inference of our result. CONCLUSION: IT fentanyl significantly decreased the incidence of shivering in women undergoing CD under spinal anesthesia without increasing maternal adverse events, confirming that routine use in this patient population is a good choice. IT sufentanil did not decrease the incidence of shivering. IT meperidine decreased the incidence and severity of shivering, but its use was also associated with significant nausea and vomiting.

Intravenous dexmedetomidine versus intravenous clonidine for post spinal anesthesia shivering: a meta-analysis of randomized controlled trials.

BACKGROUND: Dexmedetomidine and clonidine are the most extensively studied drugs for shivering treatment, because α2-adrenergic agonists can reduce the shivering threshold. The objective of this meta-analysis was to compare the efficacy and complications of dexmedetomidine with those of clonidine, when used for control of post spinal anesthesia shivering. METHODS: Electronic databases were searched for randomized controlled trials (RCT) comparing the effect of dexmedetomidine versus clonidine for control of post spinal anesthesia shivering. The endpoints were effective rate of shivering treatment, time to cease shivering, recurrent rate of shivering and complications. RESULTS: Six studies comprising 340 adult patients were included in this meta-analysis. Dexmedetomidine had higher effective rate of shivering treatment (odds ratio [OR]: 4.11, 95% confidence interval (CI): [1.53, 11.07], P = 0.005), shorter time to cease shivering (Mean differences (MD)=-1.91; 95% CI [-3.66, -0.15], P = 0.03), lower recurrent rate of shivering (OR = 0.30; 95% CI [0.12, 0.75], P = 0.01), compared to clonidine. Dexmedetomidine had a lower rate of hypotension and higher incidence of sedation than clonidine. CONCLUSIONS: Dexmedetomidine is superior to clonidine when used for shivering treatment after spinal anesthesia, because of higher incidence of effective rate and sedation, faster control of shivering, lower incidence of recurrent rate and hypotention.

The effect of combination of warm intravenous fluid infusion and forced air warming versus forced air warming alone on maternal temperature and shivering during cesarian delivery under spinal anesthesia.

Objective: Administration of warm intravenous (IV) fluid infusion and use of forced air warmers is the most easy and physiologically viable method for maintaining normothermia during surgery and postsurgical periods This study was conducted to assess the effect of combination of active warming (AW) methods namely warm IV fluid infusion and forced air warming versus forced air warming only (WA) on maternal temperature during elective C-delivery under spinal anesthesia. Materials and Methods: A total of 100 patients scheduled for elective c-section were grouped into those who received both warmed IV fluid infusion and forced air warmer (Combination of active warming WI= 50) and those who received only forced air warmer (WA = 50). Core body temperature and shivering incidence were recorded using a tympanic thermometer from prespinal till the end of surgery every 10 min and in postanesthesia care unit (PACU) at 0, 15, and 30 min. Results: Core temperature showed statistically significant difference in 15, 35, 45, and 55 min between air warmer and warm infusion groups and in PACU at 0, 15, and 30 min, it was statistically significant (P = 0.000) among WI group (mean temperature = 36.79°C) when compared to WA group (mean temperature = 35.96°C). There was a lower incidence of shivering in WI compared to WA group, which is statistically significant. Conclusion: Combination of warm Intravenous fluid infusion and Forced air warming is better than forced air warming alone. In maintaining near normal maternal core body temperature during elective cesarean section following spinal anesthesia. Combined warming method also reduces shivering incidence.

RésuméObjectif: L'administration d'une perfusion de liquide intraveineux chaud (IV) et l'utilisation de réchauffeurs à air forcé sont les plus faciles et les plus viables sur le plan physiologique méthode pour maintenir la normothermie pendant la chirurgie et les périodes post-chirurgicales Cette étude a été menée pour évaluer l'effet de la combinaison des méthodes de réchauffement actif (AW), à savoir la perfusion de liquide IV chaud et le réchauffement à air forcé par rapport au réchauffement à air forcé uniquement (WA) sur la mère la température pendant la livraison élective de C sous anesthésie rachidienne. Matériel et méthodes: Un total de 100 patients programmés pour un stage électif les césariennes ont été regroupées dans celles qui ont reçu à la fois une perfusion de liquide IV chauffée et un réchauffeur à air forcé (combinaison de réchauffement actif WI = 50) et ceux qui n'ont reçu qu'un réchauffeur d'air forcé (WA = 50). La température corporelle centrale et l'incidence des frissons ont été enregistrées en utilisant un thermomètre tympanique du préspinal jusqu'à la fin de la chirurgie toutes les 10 min et dans l'unité de soins postanesthésiques (PACU) à 0, 15 et 30 min. Résultats: La température centrale a montré une différence statistiquement significative en 15, 35, 45 et 55 min entre les groupes de réchauffement de l'air et de perfusion chaude et dans le PACU à 0, 15 et 30 min, il était statistiquement significatif (P = 0,000) dans le groupe WI (température moyenne = 36,79 ° C) en comparaison au groupe WA (température moyenne = 35,96 ° C). Il y avait une incidence plus faible de frissons dans WI par rapport au groupe WA, qui est statistiquement important. Conclusion: La combinaison de la perfusion de liquide intraveineux chaud et du réchauffement forcé de l'air est meilleure que le réchauffement forcé de l'air seul. Dans maintien d'une température corporelle maternelle près de la normale pendant la césarienne élective après anesthésie rachidienne. Réchauffement combiné La méthode réduit également l'incidence des frissons.

Prevention of postanesthetic shivering under subarachnoid block for cesarean section: A randomized, controlled study comparing tramadol versus ondansetron.

BACKGROUND: Shivering is a frequent undesirable event in patients undergoing cesarean delivery under spinal anesthesia. Postanesthetic shivering has a multitude of deleterious effects and different methods have been used to prevent it. We therefore compare the efficacy of ondansetron to that of tramadol in preventing postanesthetic shivering in women undergoing cesarean section under subarachnoid block. AIM: Comparison of the efficacy of ondansetron to that of tramadol in preventing postanesthetic shivering in women undergoing cesarean section under subarachnoid block. SUBJECT AND METHODS: This is a prospective, double-blind, placebo-controlled, randomized study. The patients (n = 109) were randomly allocated to three groups according to the study drugs, namely tramadol 50 mg group (Group T), ondansetron 4 mg group (Group O), and saline 4 ml group (Group S) using envelope randomization. Statistical analyses were done using Statistical Package for Social Sciences 20.0. RESULTS: A total of 100 patients completed the study (33 in Group S, 33 in Group T, and 34 in Group O). The three groups were comparable with respect to demographic characteristics. Shivering was observed in 16 (48.5%) of the patients in Group S; 13 (39.4%) patients in Group T, and in only 2 (5.9%) patients in Group O. The differences in incidence of shivering were statistically significant between Groups O and S (P = 0.000) and Groups O and T (P = 0.001) but not between Groups T and S (P = 0.460). The differences across the groups were not statistically significant in terms of incidence of intraoperative hypotension, bradycardia, and the cumulative amount of ephedrine consumed. CONCLUSION: This study demonstrated that ondansetron is superior to tramadol in preventing shivering under spinal anesthesia in women undergoing cesarean section.

Intravenous dexmedetomidine versus tramadol for treatment of shivering after spinal anesthesia: a meta-analysis of randomized controlled trials.

BACKGROUND: Shivering is a frequent complication after spinal anesthesia. Increasing studies have compared the effect of intravenous dexmedetomidine and intravenous tramadol on shivering after spinal anesthesia, hence we performed a meta-analysis of randomized controlled trials to compare dexmedetomidine with tramadol on the treatment of post-spinal anesthesia shivering. METHODS: PubMed, Embase, Cochrane library, Web of Science and Google Scholar were searched to find the eligible studies comparing the effect of dexmedetomidine and tramadol on the treatment of shivering after spinal anesthesia. Mean difference (MD) or risk ratio (RR) along with 95% confidence interval (CI) was used to analyze the outcomes. I2 test was conducted to assess the heterogeneity of the included trials. We utilized Review Manager 5.3 to perform statistical analyses. RESULTS: Thirteen randomized controlled trials including 864 subjects were included. Dexmedetomidine had higher effective rate of shivering control (RR =1.03; 95%CI [1.01, 1.06], P = 0.01, I2 = 14%), shorter time to cease shivering (MD = -2.14; 95%CI [- 2.79, - 1.49], P < 0.00001, I2 = 98%), lower recurrent rate of shivering (RR = 0.45; 95%CI [0.27, 0.73], P = 0.001, I2 = 0%), lower incidences of nausea (RR = 0.10; 95%CI [0.05, 0.19], P < 0.00001, I2 = 48%), and vomiting (RR = 0.13; 95%CI [0.06, 0.30], P < 0.00001, I2 = 0%), higher incidence of sedation (RR = 2.48; 95%CI [1.32, 4.65], P = 0.005, I2 = 82%), hypotension (RR = 2.50; 95%CI [1.24, 5.03], P = 0.01, I2 = 0%) and bradycardia (RR = 4.78; 95%CI [1.76, 13.00], P = 0.002, I2 = 0%), compared with tramadol. CONCLUSIONS: Dexmedetomidine is superior to tramadol for shivering treatment, due to higher effective rate of shivering control, earlier onset of action and lesser recurrence of shivering with higher incidence of sedation and lower incidences of nausea and vomiting. However, dexmedetomidine is also associated with higher incidences of hypotension and bradycardia than tramadol.

Control of Shivering During Targeted Temperature Management.

Targeted temperature management (TTM) is used frequently in patients with a variety of diseases, especially those who have experienced brain injury and/or cardiac arrest. Shivering is one of the main adverse effects of TTM that can often limit its implementation and efficacy. Shivering is the body's natural response to hypothermia and its deleterious effects can negate the benefits of TTM. The purpose of this article is to provide an overview of TTM strategies and shivering management.

Fetal and Maternal Responses to Dexmedetomidine Intrathecal Application During Cesarean Section: A Meta-Analysis.

BACKGROUND Intrathecal dexmedetomidine (DEX) can improve the blockade of spinal anesthesia, but there is no clear conclusion on whether it has an effect on the fetus during cesarean section. Our meta-analysis evaluated the safety and efficacy of intrathecal DEX in cesarean delivery. MATERIAL AND METHODS We searched Cochrane, Embase, PubMed, and CBM for eligible studies, and used the Revised Cochrane Risk of Bias Tool (RoB 2.0) to assess the risk of bias of each study. RevMan was used for statistical analyses. We have registered this meta-analysis on PROSPERO (CRD42019120995). RESULTS The meta-analysis included 10 RCTs, but only 5 were prospectively registered. The results of preregistration studies, including the 1- or 5-min Apgar score (mean difference [MD], -0.03; 95% confidence intervals [CI], -0.16 to 0.10; P=0.64 or MD, 0.00; 95% CI, -0.09 to 0.09; P=1), the umbilical arterial oxygen or carbon dioxide partial pressure (MD, 0.90; 95% CI, -4.92 to 6.72; P=0.76 or MD, 1.20; 95% CI, -2.06 to 4.46; P=0.47), and the cord blood pH (MD, -0.01; 95% CI, -0.05 to 0.03; P=0.72), showed that intrathecal DEX had no significant difference in neonatal outcomes compared with placebo. In maternal outcomes, intrathecal DEX significantly prolonged postoperative pain-free period and reduced the incidence of postoperative shivering, which did not increase spinal anesthesia-associated adverse effects. CONCLUSIONS Intrathecal DEX is safe for the fetus during cesarean section and can improve the blockade effects of spinal anesthesia on puerperae.

Risk factors for shivering during caesarean section under spinal anaesthesia. A prospective observational study.

BACKGROUND: Shivering during caesarean section (CS) under spinal anaesthesia is a common phenomenon. It could not only alter patient's physiology by increasing oxygen consumption but also affect the parturient's experience of childbirth. Shivering is thought to be associated with intraoperative hypothermia, but the risk factors and exact mechanism remain unclear. METHODS: We conducted a prospective, observational study to examine the potential risk factors for intraoperative shivering, including anxiety levels. Two hundred patients undergoing elective CS under spinal anaesthesia were recruited. Parturient anxiety levels were evaluated using the State-Trait Anxiety Inventory (STAI) questionnaire. Age, weight, height, BMI, anxiety level, number of previous deliveries, sensory block level, level of education, temperature difference during surgery and American Society of Anesthesiologists score were investigated as potential risk factors. Stepwise logistic regression was used to assess the predictors for shivering. RESULTS: Data from 155 parturients were analysed. Shivering incidence was 21.9% (34 parturients). The statistical model predicted 8.5% of a shivering incidence variability (R-square Nagelkerke = 0.085). Out of all measured variables, only the number of previous deliveries [(W) = 4.295 Exp(B) = 0.562 P < .05] and STAI-X1 [(W) = 4.127 Exp(B) = 1.052 P < .05] were significant. In our model, the risk of shivering decreased by 44% with every previous delivery and increased by 5.2% with each 1-point increase in STAI-X1. CONCLUSION: We failed to prove a strong correlation between the measured variables and shivering. Our findings, however, support the hypothesis, that to a limited extent, anxiety promotes shivering during CS.

Effects of Perioperative Administration of Acetaminophen on Postoperative Shivering: A Randomized, Triple-Blind, Placebo-Controlled Trial.

BACKGROUND: In this randomized, triple-blind, placebo-controlled trial, we tested the hypothesis that perioperative acetaminophen administration has a prophylactic effect on postoperative shivering. METHODS: Forty-five women scheduled for gynecological laparotomy were randomized to either the acetaminophen or the placebo groups. After induction of general anesthesia, the test drug (acetaminophen 15 mg/kg) or placebo (0.9% saline) was intravenously administered over 15 minutes. The primary outcome measure was the incidence of severe postoperative shivering (ie, shivering score >2) in the postanesthesia care unit, where patients stayed for 30 minutes after their emergence from anesthesia. For the secondary outcomes, core body temperature (BT) was recorded at the forehead just before anesthesia induction (time 0 [T0]), at the start of surgery (time 1 [T1]), at the end of surgery (time 2 [T2]), at the initiation of postoperative observation in the postanesthesia care unit (time 3 [T3]), and 30 minutes after T3 (time 4 [T4]). At 1 hour after T4 (ie, time 5 [T5]), the BT was recorded from the axilla (BTA). Primary outcome was analyzed using a χ test. BT recorded at the forehead (BTF) and BTA were analyzed using a 2-way repeated-measures analysis of variance (ANOVA) and a 2-sample t test, respectively. For all comparisons, a P value <.05 was considered statistically significant. RESULTS: The study duration was 2 years. Of the 45 patients initially enrolled, 8 patients were excluded. The acetaminophen and placebo groups included 18 and 19 patients, respectively. The incidence of severe postoperative shivering in the postanesthesia care unit was significantly lower in the acetaminophen group (22.2%) than in the placebo group (73.7%) (relative risk, 0.302; 95% confidence interval, 0.122-0.746; P = .005). Two-way repeated-measures ANOVA showed a significant effect of time (F4,140 = 54.8; P < .001) and a significant time by treatment interaction (F4,140 = 9.61; P < .001) but did not show a main effect of the treatment (F1,35 = 1.83; P = .185) in BTF. Moreover, BTA at T5 was significantly lower in the acetaminophen group (mean [standard deviation {SD}], 37.2°C [0.48°C]) than in the placebo group (37.9°C [0.63°C]; P < .001). CONCLUSIONS: Our findings in patients undergoing gynecological laparotomy suggest that perioperative acetaminophen administration can prevent postoperative severe shivering. This prophylactic effect might be due to suppressing the postoperative increase in the BT set point, rather than lowering the threshold for shivering, as observed with clonidine.

Comparison of nalbuphine, ondansetron and placebo for the prevention of shivering after spinal anaesthesia for urgent caesarean delivery: a randomised double-blind controlled clinical trial.

BACKGROUND: Shivering is a common complication of caesarean delivery with neuraxial anaesthesia. The effective prevention and treatment of shivering, especially before delivery, is important and difficult. We tested the hypothesis that prophylactic nalbuphine and ondansetron can prevent post-spinal anaesthesia shivering in parturients undergoing urgent caesarean delivery. METHODS: Sixty parturients scheduled for urgent caesarean delivery before spinal anaesthesia were selected and divided randomly into three groups. After peripheral venous catheterisation, parturients were given intravenous nalbuphine 0.08 mg/kg (group N), ondansetron 8 mg (group O), or normal saline (group C). RESULTS: The incidence of shivering and of severe (grade ≥3) shivering was significantly lower in group N (15% and 15%, respectively) than in group C (80% and 65%) before delivery (P <0.001 and P=0.003); and significantly less shivering was observed in group N than in group C in the first 30 min after anaesthesia (P=0.001). Up to 60 min after anaesthesia, the incidence of grade ≥3 shivering remained lowest in group N (P=0.003). According to the data during the period from anaesthesia until delivery, the number needed-to-treat for nalbuphine was 1.54 (95%CI 1.13 to 2.41). No significant differences were found between groups O and N or groups O and C at any time. The incidence of dizziness in group N was significantly higher than that of groups O or C (P=0.009). CONCLUSION: Nalbuphine 0.08 mg/kg can prevent post-spinal anaesthesia shivering in parturients undergoing urgent caesarean delivery but causes transient dizziness, while ondansetron 8 mg had no significant effect.

Autonomic effects induced by pharmacological activation and inhibition of Raphe Pallidus neurons in anaesthetized adult pigs.

The Raphe Pallidus (RPa) is a region of the brainstem that was shown to modulate the sympathetic outflow to many tissues and organs involved in thermoregulation and energy expenditure. In rodents, the pharmacological activation of RPa neurons was shown to increase the activity of the brown adipose tissue, heart rate, and expired CO2 , whereas their inhibition was shown to induce cutaneous vasodilation and a state of hypothermia that, when prolonged, leads to a state resembling torpor referred to as synthetic torpor. If translatable to humans, this synthetic torpor-inducing procedure would be advantageous in many clinical settings. A first step to explore such translatability, has been to verify whether the neurons within the RPa play the same role described for rodents in a larger mammal such as the pig. In the present study, we show that the physiological responses inducible by the pharmacological stimulation of RPa neurons are very similar to those observed in rodents. Injection of the GABAA agonist GABAzine in the RPa induced an increase in heart rate (from 99 to 174 bpm), systolic (from 87 to 170 mm Hg) and diastolic (from 51 to 98 mm Hg) arterial pressure, and end-tidal CO2 (from 49 to 62 mm Hg). All these changes were reversed by the injection in the same area of the GABAA agonist muscimol. These results support the possibility for RPa neurons to be a key target in the research for a safe and effective procedure for the induction of synthetic torpor in humans.

Subarachnoid and epidural dexmedetomidine for the prevention of post-anesthetic shivering: a meta-analysis and systematic review.

BACKGROUND: Post-anesthetic shivering incurs discomfort to patients or even exacerbates their condition. However, no ideal drug has been well established for preventing post-anesthetic shivering. Currently, subarachnoid and epidural dexmedetomidine have demonstrated to have an anti-shivering effect. METHODS: An electronic search was conducted to identify randomized placebo-controlled trials reporting shivering and then compared subarachnoid and epidural dexmedetomidine with placebo in adults undergoing selective surgery. Data assessment and pooling were analyzed by Review Manager 5.3, STATA 15.0 and GRADE-pro 3.6 software. RESULTS: Twenty-two studies (1389 patients) were subjected to this meta-analysis. The incidence of post-anesthetic shivering decreased from 20.10% in the placebo group to 10.30% in the dexmedetomidine group (RR, 0.48; 95% CI, 0.39-0.59; Z=6.86, P<0.00001, I 2=32%). Non-Indian, epidural-space route and cesarean subgroups indicated a better anti-shivering effect. In the subarachnoid-space route subgroup, a dosage of >5 µg showed significantly superior anti-shivering effects than that of ≤5 µg. Subarachnoid and epidural dexmedetomidine increased the incidence of bradycardia, had no impact on nausea and vomiting, shortened the onset of block and lengthened the duration of block and analgesia. However, its effect on hypotension and sedation remained uncertain. The overall risk of bias was relatively low. The level of evidence was high, and the recommendation of voting results was strong. CONCLUSION: Dexmedetomidine as a subarachnoid and epidural adjunct drug could decrease the incidence of post-anesthetic shivering in a dose-dependent manner. However, caution should be taken in patients with original bradycardia.

Pharmacological Approach for the Prevention of Postoperative Shivering: A Systematic Review of Prospective Randomized Controlled Trials

Shivering is a common postoperative complication that occurs after both general and regional anesthesia even in the cases when hypothermia during surgery has been averted. Patients describe it as a highly unpleasant experience, while clinicians are concerned due to its adverse effects such as increased oxygen consumption. In this article, we present a summary of the pathophysiological mechanisms involved in postoperative shivering (POS), risk factors, and inadvertent effects. The major objective of this article was to review the existing literature on the effi ciency of various drug interventions as a prophylactic measure against POS. Since α2-adrenergic, opioid, anticholinergic, and serotonergic pathways are thought to play a role in the pathogenesis of POS, a wide variety of drugs has been investigated in this regard. Although the methodological diversity of the study designs and regimens does not support drawing defi nite conclusions, there is evidence indicating a benefi cial effect of dexmedetomidine, ketamine, tramadol, meperidine, dexamethasone, nefopam, granisetron, and ondansetron in the prevention of POS. The purpose of this review is to provide a thorough insight on various drug options and to serve as an aid for clinicians for careful analysis of the advantages and disadvantages of each regimen to decide which regimen will be ideally suited for the medical profi le of each patient.