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1.  Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study 
Critical Care  2007;11(1):R29.
Mild therapeutic hypothermia has been shown to improve outcome for patients after cardiac arrest and may be beneficial for ischaemic stroke and myocardial ischaemia patients. However, in the awake patient, even a small decrease of core temperature provokes vigorous autonomic reactions–vasoconstriction and shivering–which both inhibit efficient core cooling. Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. We tested whether a combination of skin warming and a medium dose of meperidine additively would reduce the shivering threshold to below 34°C without producing significant sedation or respiratory depression.
Eight healthy volunteers participated on four study days: (1) control, (2) skin warming (with forced air and warming mattress), (3) meperidine (target plasma level: 0.9 μg/ml), and (4) skin warming plus meperidine (target plasma level: 0.9 μg/ml). Volunteers were cooled with 4°C cold Ringer lactate infused over a central venous catheter (rate ≈ 2.4°C/hour core temperature drop). Shivering threshold was identified by an increase of oxygen consumption (+20% of baseline). Sedation was assessed with the Observer's Assessment of Alertness/Sedation scale.
Control shivering threshold was 35.5°C ± 0.2°C. Skin warming reduced the shivering threshold to 34.9°C ± 0.5°C (p = 0.01). Meperidine reduced the shivering threshold to 34.2°C ± 0.3°C (p < 0.01). The combination of meperidine and skin warming reduced the shivering threshold to 33.8°C ± 0.2°C (p < 0.01). There were no synergistic or antagonistic effects of meperidine and skin warming (p = 0.59). Only very mild sedation occurred on meperidine days.
A combination of meperidine and skin surface warming reduced the shivering threshold to 33.8°C ± 0.2°C via an additive interaction and produced only very mild sedation and no respiratory toxicity.
PMCID: PMC2151895  PMID: 17316456
2.  Dantrolene Reduces the Threshold and Gain for Shivering 
Anesthesia and analgesia  2004;98(5):1318-contents.
Dantrolene is used for treatment of life-threatening hyperthermia, yet its thermoregulatory effects are unknown. We tested the hypothesis that dantrolene reduces the threshold (triggering core temperature) and gain (incremental increase) of shivering. With IRB approval and informed consent, healthy volunteers were evaluated on two random days: control and dantrolene (≈2.5 mg/kg plus a continuous infusion). In study 1, 9 men were warmed until sweating was provoked and then cooled until arterio-venous shunt constriction and shivering occurred. Sweating was quantified on the chest using a ventilated capsule. Absolute right middle fingertip blood flow was quantified using venous-occlusion volume plethysmography. A sustained increase in oxygen consumption identified the shivering threshold. In study 2, 9 men were given cold Ringer's solution IV to reduce core temperature ≈2°C/h. Cooling was stopped when shivering intensity no longer increased with further core cooling. The gain of shivering was the slope of oxygen consumption vs. core temperature regression. In Study 1, sweating and vasoconstriction thresholds were similar on both days. In contrast, shivering threshold decreased 0.3±0.3°C, P=0.004, on the dantrolene day. In Study 2, dantrolene decreased the shivering threshold from 36.7±0.2 to 36.3±0.3°C, P=0.01 and systemic gain from 353±144 to 211±93 ml·min−1·°C−1, P=0.02. Thus, dantrolene substantially decreased the gain of shivering, but produced little central thermoregulatory inhibition.
PMCID: PMC1454474  PMID: 15105208
Temperature: hyperthermia, fever; Pharmacology: dantrolene; Complications: shivering
3.  Doxapram Only Slightly Reduces the Shivering Threshold in Healthy Volunteers 
Anesthesia and analgesia  2005;101(5):1368-1373.
We determined the effects of doxapram on the major autonomic thermoregulatory responses in humans. Nine healthy volunteers were studied on two days: Control and Doxapram (intravenous infusion to a plasma concentration of 2.4 ±0.8 μg/mL, 2.5 ±0.9 μg/mL, and 2.6 ±1.1 μg/mL at the sweating, vasoconstriction, and shivering thresholds, respectively). Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the sweating, vasoconstriction, and shivering thresholds with compensation for changes in skin temperature. Data were analyzed with paired t tests and presented as means ± SDs; P < 0.05 was considered statistically significant. Doxapram did not change the sweating (Control: 37.5±0.4°C, Doxapram: 37.3±0.4°C, P=0.290) or the vasoconstriction threshold (36.8±0.7 vs. 36.4±0.5°C; P=0.110). However, it significantly reduced the shivering threshold from 36.2±0.5 to 35.7±0.7°C (P=0.012). No sedation or symptoms of panic were observed on either study day. The observed reduction in the shivering threshold explains the drug's efficacy for treatment of postoperative shivering; however, a reduction of only 0.5°C is unlikely to markedly facilitate induction of therapeutic hypothermia as a sole agent.
PMCID: PMC1552102  PMID: 16243996
Anesthesia; Hypothermia; Temperature; Thermoregulation
4.  Ondansetron Does Not Reduce the Shivering Threshold in Healthy Volunteers 
British journal of anaesthesia  2006;96(6):732-737.
Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (trigging core temperatures) in humans.
Ten healthy volunteers were studied on two days: Control and Ondansetron (intravenous infusion to plasma concentrations of 278 (57) ng mL−1, 234 (55) ng mL−1, and 243 (58) ng mL−1at the sweating, vasoconstriction, and shivering thresholds, respectively); this corresponded to ≈50 mg of ondansetron which is roughly ten times the dose used for postoperative nausea and vomiting. Each day, skin and core temperatures were increased to provoke sweating, then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction, and shivering thresholds after compensating for changes in mean-skin temperature. Data were analyzed with paired t tests and presented as means (SD)s; P<0.05 was statistically significant.
Ondansetron did not change the sweating (Control: 37.4 (0.4)°C, Ondansetron: 37.6 (0.3)°C, P=0.16), vasoconstriction (37.0 (0.5) vs. 37.1 (0.3)°C; P=0.70), or shivering threshold (36.3 (0.5) vs. 36.3 (0.6)°C; P=0.76). No sedation was observed on either study day.
Ondansetron, therefore, appears to have little potential for facilitating induction of therapeutic hypothermia.
PMCID: PMC1502385  PMID: 16675509
Thermoregulation; ondansetron; therapeutic hypothermia
5.  Intrathecal injection of magnesium sulfate: shivering prevention during cesarean section: a randomized, double-blinded, controlled study 
Korean Journal of Anesthesiology  2013;65(4):293-298.
Regional anesthesia is known to significantly impair thermoregulation and predispose patients to hypothermia. We hypothesized that the addition of an intrathecal injection of magnesium sulfate (MgSO4) to bupivacaine would improve perioperative shivering in female patients undergoing elective caesarean section.
In a block-randomized, double-blinded, controlled trial 72 patients scheduled for elective caesarean section with spinal anesthesia were separated into two groups. In the treatment group, 2 ml of 0.5% bupivacaine plus 25 mg MgSO4 (0.5 ml) were injected intrathecally, and in the control group 2 ml of 0.5% bupivacaine plus 0.5 ml normal saline were injected intrathecally. Core temperature was measured before and after drug injection at predetermined intervals. Sedation was graded using the Ramsay sedation scale.
No significant intergroup differences in appearance of shivering were seen immediately or at 5, 30, 40, 50, 60, and 90 min after block administration. However, at 10, 15, and 20 min post block, there was a significant difference in shivering. The group administered MgSO4 showed lower shivering grades compared with the control group. Core temperature was significantly reduced in the MgSO4 group compared to the normal saline group 30 min after blocking.
Intrathecal injection of MgSO4 improved perioperative shivering in female patients undergoing elective caesarean section.
PMCID: PMC3822019  PMID: 24228140
Bupivacaine; Cesarean section; Magnesium sulfate; Shivering
6.  The Effect of Postoperative Skin-Surface Warming on Oxygen Consumption and the Shivering Threshold 
Anaesthesia  2003;58(12):1228-1234.
Cutaneous warming is reportedly an effective treatment for shivering during epidural and after general anaesthesia. We quantified the efficacy of cutaneous warming as a treatment for shivering. Unwarmed surgical patients (final intraoperative core temperatures ≈35°C) were randomly assigned to be covered with a blanket (n=9) or full-body forced-air cover (n=9). Shivering was evaluated clinically and by oxygen consumption. Forced-air heating increased mean-skin temperature (35.7±0.4 °C vs. 33.2±0.8°C, P< 0.0001) and lowered core temperature at the shivering threshold (35.7±0.2 °C vs. 36.4±0.2°C, P< 0.0001). Active warming improved thermal comfort and significantly reduced oxygen consumption from 9.7±4.4 to 5.6±1.9 mL·min−1·kg−1(P=0.038). However, duration of shivering was similar in the two groups (37±11 min [warming] and 36±10 min [control]). Core temperature thus contributed about four times as much as skin temperature to control of shivering. Cutaneous warming improved thermal comfort and reduced metabolic stress in postoperative patients, but did not quickly obliterate shivering.
PMCID: PMC1314985  PMID: 14705689
shivering; body temperature; thermoregulatory control
7.  Prophylactic Granisetron Vs Pethidine for the Prevention of Postoperative Shivering: A Randomized Control Trial 
Indian Journal of Anaesthesia  2009;53(3):330-334.
Shivering-the “Big Little Problem” has an incidence of 60% in early recovery phase following general anaesthesia. A number of techniques have been tried to prevent postoperative shivering. Previous study showed that, ondansetron in higher doses reduces postoperative shivering. Therefore, this study was done to compare the efficacy of prophylactic granisetron, pethidine and placebo in preventing postoperative shivering.
Ninety patients aged 20-60yrs, ASA physical status I and II, scheduled for laparoscopic surgery under general anaesthesia were randomly allocated to receive either normal saline (Group S, n=30) as negative control, pethidine 25mg (Group P, n=30) as positive control or granisetron−1 (Group G, n=30) intravenously before induction. The anaesthesia was induced with fentanyl−1, propofol−1 and atracurium−1 and maintained with sevoflurane 1 - 1.5%. Nasopharyngeal temperature was measured throughout the procedure. An investigator, blinded to the treatment group, graded postoperative shivering in a scale of 0 to 4. (0= no shivering, 1= piloerection or peripheral vasoconstriction but no visible shivering, 2= muscle activity in only one muscle group 3= muscle activity in more than one muscle group, 4= shivering involving the whole body). Prophylaxis was regarded as ineffective if shivering was greater than grade 3 and intravenous pethidine 25 mg was administered as rescue medication.
The three groups did not differ significantly regarding patient characteristics. The numbers of patients shivering on arrival in the recovery room at 15 minutes after operation were significantly less in Group P (7%) and Group G (17%) than in Group S (60%). Groups P and G differ significantly than in Group S (p<0.05). However, the difference between Groups P and G was not statistically significant (p>0.05). The prophylactic use of granisetron (−1) and pethidine(25mg) intravenous were found to be effective in preventing postoperative shivering.
PMCID: PMC2900125  PMID: 20640142
Shivering; Postoperative; Granisetron; Pethidine
8.  Nefopam, a Non-sedative Benzoxazocine Analgesic, Selectively Reduces the Shivering Threshold 
Anesthesiology  2004;100(1):37-43.
The analgesic nefopam does not compromise ventilation, is minimally sedating, and is effective as a treatment for postoperative shivering. We evaluated the effects of nefopam on the major thermoregulatory responses in humans: sweating, vasoconstriction, and shivering.
Nine volunteers were studied on three randomly assigned days: 1) control (Saline), 2) nefopam at a target plasma concentration of 35 ng/ml (Small Dose), and 3) nefopam at a target concentration of 70 ng/ml (Large Dose, ≈20 mg total). Each day, skin and core temperatures were increased to provoke sweating and then reduced to elicit peripheral vasoconstriction and shivering. We determined the thresholds (triggering core temperature at a designated skin temperature of 34°C) by mathematically compensating for changes in skin temperature using the established linear cutaneous contributions to control of each response.
Nefopam did not significantly modify the slopes for sweating (0.0 ± 4.9°C·μg−1·ml; r2 = 0.73 ± 0.32) or vasoconstriction (−3.6 ± 5.0°C·μg−1·ml; r2=−0.47± 0.41). In contrast, nefopam significantly reduced the slope of shivering (−16.8 ± 9.3°C·μg−1·ml; r2 = 0.92 ± 0.06). Large-Dose nefopam thus reduced the shivering threshold by 0.9 ± 0.4°C (P<0.001) without any discernable effect on the sweating or vasoconstriction thresholds.
Most drugs with thermoregulatory actions — including anesthetics, sedatives, and opioids — synchronously reduce the vasoconstriction and shivering thresholds. Nefopam however reduced only the shivering threshold. This pattern has not previously been reported for a centrally acting drug. That pharmacologic modulation of vasoconstriction and shivering can be separated is of clinical and physiologic interest.
PMCID: PMC1283107  PMID: 14695722
Temperature; Thermoregulation; Nefopam; Shivering; Vasoconstriction; Threshold; Hypothermia
9.  Nonpharmacologic Approach to Minimizing Shivering During Surface Cooling: A Proof of Principle Study1  
Journal of critical care  2012;27(6):746.e1-746.e8.
This study had two objectives: (1) to quantify the metabolic response to physical cooling in febrile patients with Systemic Inflammatory Response Syndrome (SIRS); and (2) to provide proof for the hypothesis that the efficiency of external cooling and the subsequent shivering response are influenced by site and temperature of surface cooling pads.
To quantify shivering thermogenesis during surface cooling for fever, we monitored oxygen consumption (VO2) in six febrile patients with SIRS during conventional cooling with cooling blankets and ice packs. To begin to determine how location and temperature of surface cooling influences shivering, we compared 5 cooling protocols for inducing mild hypothermia in six healthy volunteers.
In the SIRS patients, core temperature decreased 0.67°C per hour, all patients shivered, VO2 increased 57.6% and blood pressure increased 15% during cooling. In healthy subjects, cooling with the 10°C vest was most comfortable and removed heat most efficiently without shivering or VO2 increase. Cooling with combined vest and thigh pads stimulated the most shivering and highest VO2, and increased core temperature. Reducing vest temperature from 10°C to 5°C failed to increase heat removal secondary to cutaneous vasoconstriction. Capsaicin, an agonist for TRPV1 warm-sensing channels, partially reversed this effect in 5 subjects.
Our results identify the hazards of surface cooling in febrile critically ill patients and support the concept that optimization of cooling pad temperature and position may improve cooling efficiency and reduce shivering.
PMCID: PMC3494806  PMID: 22762936
Fever; Hypothermia; Surface Cooling; Shivering
10.  Induction of a Prolonged Hypothermic State by Drug-induced Reduction in the Thermoregulatory Set-Point 
The marked improvement in outcome following induction of hypothermia after cardiac arrest has spurred the search for better methods to induce cooling. A regulated decrease in core temperature mediated by a drug-induced reduction in the set point for thermoregulation may be an ideal means of inducing hypothermia. To this end, the exploratory drug HBN-1 was assessed as a means to induce mild and prolonged hypothermia.
Free moving rats were infused i.v. for 12 hours with: a vehicle at room temperature (normothermia), a vehicle chilled to 4°C (forced hypothermia), or HBN-1 (mixture of ethanol, lidocaine, and vasopressin) at room temperature. Core (intra-abdominal) temperature (Tc) was measured telemetrically, tail skin temperature (Ttail) by infrared thermography, metabolic rate (MR) was estimated with indirect calorimetery, and shivering was scored visually.
HBN-1 elicited a reduction in Tc from 37.5°C to 34°C within 80 minutes after initiation of the infusion; Tc was maintained between 33°C and 34°C for more than 13 hours. HBN-1 infusion was associated with a reduction in MR (p=0.0006), a slight reduction in Ttail, and no evidence of shivering (p<0.001). The forced hypothermia group displayed shivering (p<0.001), a significant increase in MR, and a decrease in Ttail, indicative of peripheral vasoconstriction to reduce heat loss.
HBN-1 infusion induced a mild and prolonged hypothermia in free moving, unanesthetized rats characterized by modulation of thermoeffectors to reduce heat gain and increase heat loss. HBN-1 thus appears to elicit regulated hypothermia and may provide a new method for achieving a prolonged state of therapeutic hypothermia.
PMCID: PMC3621333  PMID: 23667774
11.  Effect of ramosetron on shivering during spinal anesthesia 
Korean Journal of Anesthesiology  2010;58(3):256-259.
Shivering associated with spinal anesthesia is uncomfortable and may interfere with monitoring. The aim of this study is to evaluate the effect of ramosetron, a serotonin-3 receptor antagonist, on the prevention of shivering during spinal anesthesia.
We enrolled 52 patients who were ASA I or II and who had undergone knee arthroscopy under spinal anesthesia. Warmed (37°) lactated Ringer's solution was infused over 15 minutes before spinal anesthesia. Patients were randomly allocated to a control group (group S, N = 26) or study group (group R, N = 26). Spinal anesthesia was performed with a 25-G Quincke-type spinal needle between the lumbar 3-4 interspace with 2.2 ml 0.5% hyperbaric bupivacaine. For patients allocated in groups S and R, 2 ml 0.9% saline and 0.3 mg ramosetron, respectively, was intravenously injected immediately before intrathecal injection at identical times. Shivering and spinal block levels were assessed immediately after the completion of subarachnoid injection, as well as 5, 10, 15, 20, 25, 30, 60, and 120 minutes after spinal anesthesia. Systolic and diastolic blood pressures, heart rate, and peripheral oxygen saturation were also recorded. Core temperatures were measured by tympanic thermometer and recorded before and during spinal anesthesia at 30-minute intervals.
Shivering was observed in 2 patients in group R and 9 patients in group S (P = 0.038, odds ratio = 6.14, 95% C.I. = 1.08-65.5). The difference in core temperature between the groups was not significant.
Compared to control, ramosetron is an effective way to prevent shivering during spinal anesthesia.
PMCID: PMC2872836  PMID: 20498774
Ramosetron; Shivering; Spinal anesthesia; Thermoregulation
12.  Pre-induction low dose pethidine does not decrease incidence of postoperative shivering in laparoscopic gynecological surgeries 
The incidence of shivering in patients undergoing a laparoscopic procedure is stated to be about 40%. A majority of laparoscopic gynecological procedures are taken up on an outpatient basis. Postoperative shivering may delay hospital discharge and is a common cause of discomfort in patients recovering from anesthesia.
To determine the effect of pre-induction, low-dose pethidine on postoperative shivering in patients undergoing laparoscopic gynecological surgeries.
Setting and Design:
Sixty females between 25 and 35 years of age, of American Society of Anesthesiologists (ASA) class 1 and 2, were randomly divided into three groups of 20 patients each. Group I and II patients received i.v. pethidine 0.3 mg/kg and 0.5 mg/kg, respectively, while Group III received i.v. 0.9% normal saline just before induction of general anesthesia. Temperature of the Operating Room and the Post Anesthesia Care Unit was standardized and all fluids given during the study period were warmed to 37°C.
Materials and Methods:
Temperature, measured with a tympanic membrane probe, was recorded preoperatively, after induction of anesthesia, on arrival at the Post Anesthesia Care Unit, and postoperatively at 15 minutes and 30 minutes. Shivering was graded (0 – 4 scale) at arrival of the patients to the PACU and every five minutes thereafter, up to 30 minutes.
Statistical Analysis:
ANOVA, Chi-square test, Kruskal-Wallis ANOVA and Mann-Whitney U tests were used. A P-value of less than 0.05 was considered significant.
Core body temperatures were statistically insignificant between groups at pre-induction, post-induction, and in the PACU (P > 0.05). At the end of surgery, shivering was present in 18 patients (30%). In groups I, II, and III, six (30%), three (15%), and nine (45%) patients shivered, respectively. The differences in incidence and grading of shivering among groups was found to be statistically insignificant (P > 0.05). The core body temperature of shiverers and non-shiverers were compared. In the PACU at 0, 15, and 30 minutes, the temperature among shiverers was significantly lower than that in the non-shiverers. Rescue drug i.v. pethidine 20 mg was given to patients with shivering grade ≥2. None of the patients had shivering after 10 minutes.
Prophylactic pre-induction, low-dose pethidine does not have major role in preventing postoperative shivering.
PMCID: PMC3161460  PMID: 21897506
Laparoscopy; pethidine; postoperative shivering
13.  Prophylactic Low Dose Ketamine and Ondansetron for Prevention of Shivering During Spinal Anaesthesia 
Perioperative shivering is a common problem during anaesthesia. Apart from physical warming many drugs have also been used for prevention of shivering. Ketamine has been used for preventing shivering during anaesthesia in doses of 0.5 to 0.75mg kg-1, but even these doses causes too much sedation and hallucination. Ondansetron (8 mg) has been recently evaluated for its perioperative antishivering effect in patients under anaethesia. Present study was conducted to evaluate the efficacy and safety of low dose Ketamine (0.25mg kg-1) and Ondansetron (4 mg) for prevention of shivering during spinal anaesthesia.
Patients & Methods:
Total 120 patients undergoing lower abdominal surgery under spinal anaesthesia were included. 3ml of hyperbaric bupivacaine 0.5% was used for spinal anaesthesia. After intrathecal injection, the patients were randomly divided in 3 groups of 40 each who received Ketamine 0.25mg kg-1or Ondansetron 4mg IV or Saline. Vitals, temperature and shivering scores were recorded every 5 minutes. Side effects i.e. hypotension, nausea and vomiting, sedation and hallucinations were also recorded.
Fall in temperature was more significant in saline and ondansetron group (gp) than in ketamine group at all time interval. Out of 40 patients, shivering was maximum & seen in 17 patients (42.50%) in saline gp, 4 patients (10%) in ondansetron gp and in only 1patient (2.5%) in ketamine gp. Odd ratio of ketamine, ondansetron and saline are 1, 4.33 and 28.33 respectively which means that shivering in saline gp was 28.83 times higher than ketamine gp and 6.65 times higher than in ondansetron .Shivering rate was 4.33 times higher in ondansetron gp than in ketamine gp. Hypotension was lowest in ketamine gp (10%) in comparison to ondansetron gp (22.5%) and saline gp. (20%). Mild sedation was seen in almost all (95%) patients in ketamine gp,
Prophylactic low dose ketamine (0.25mg kg-1) and Ondansetron (4mg) significantly decreased shivering in patients undergoing spinal anaesthesia without significant side effects.
PMCID: PMC3087257  PMID: 21547171
Shivering; Spinal anaesthesia; Ketamine; Ondansetron
14.  Active core rewarming avoids bioelectrical impedance changes in postanesthetic patients 
BMC Anesthesiology  2011;11:2.
Postoperative hypothermia is a common cause of complications in patients who underwent laparoscopic cholecystectomy. Hypothermia is known to elicit electrophysiological, biochemical, and cellular alterations thus leading to changes in the active and passive membrane properties. These changes might influence the bioelectrical impedance (BI). Our aim was to determine whether the BI depends on the core temperature.
We studied 60 patients (52 female and 8 male) age 40 to 80 years with an ASA I-II classification that had undergone laparoscopic cholecystectomy under balanced inhalation anesthesia. The experimental group (n = 30) received active core rewarming during the transanesthetic and postanesthesic periods. The control group (n = 30) received passive external rewarming. The BI was recorded by using a 4-contact electrode system to collect dual sets of measurements in the deltoid muscle. The body temperature, hemodynamic variables, respiratory rate, blood-gas levels, biochemical parameters, and shivering were also measured. The Mann-Whitney unpaired t-test was used to determine the differences in shivering between each group at each measurement period. Measurements of body temperature, hemodynamics variables, respiratory rate, and BI were analyzed using the two-way repeated-measures ANOVA.
The gradual decrease in the body temperature was followed by the BI increase over time. The highest BI values (95 ± 11 Ω) appeared when the lowest values of the temperature (35.5 ± 0.5°C) were reached. The active core rewarming kept the body temperature within the physiological range (over 36.5°C). This effect was accompanied by low stable values (68 ± 3 Ω) of BI. A significant decrease over time in the hemodynamic values, respiratory rate, and shivering was seen in the active core-rewarming group when compared with the controls. The temporal course of shivering was different from those of body temperatue and BI. The control patients showed a significant increase in the serum-potassium levels, which were not seen in the active-core rewarming group.
The BI analysis changed as a function of the changes of core temperature and independently of the shivering. In addition, our results support the beneficial use of active core rewarming to prevent accidental hypothermia.
PMCID: PMC3053227  PMID: 21324200
15.  Effect of irrigation fluid temperature on core temperature and hemodynamic changes in transurethral resection of prostate under spinal anesthesia 
Hypothermia is a frequent observation in elderly males undergoing transurethral resection of prostate (TURP) under spinal anesthesia. The use of irrigating fluids at room temperature results in a decrease body temperature. Warmed irrigating solutions have shown to reduce heat loss and the resultant shivering. Such investigation was not much tried in low resource settings.
To compare the resultant change in core temperature and hemodynamic changes among patients undergoing TURP surgery under spinal anesthesia using warm and room temperature irrigation fluids.
Settings and Design:
Randomized prospective study at a tertiary care center.
This study was conducted on 40 male patients aged 50-85 years undergoing TURP under spinal anesthesia. Of which, 20 patients received irrigation fluid at room temperature 21°C and 20 patients received irrigation fluid at 37°C after random allocation. Core temperatures and hemodynamic parameters were assessed in all patients at preoperative, intra-operative, and postoperative periods. Intra-operative shivering was also noted in both groups.
Statistical Analysis:
Unpaired and Paired Student's t-test.
For patients who underwent irrigation with fluid at room temperature Core temperature drop from 36.97°C in preoperative to 34.54°C in postoperative period with an effective difference of 2.38°C. Among patients who received warmed irrigation fluid at 37°C had core temperature drop from 36.97°C to 36.17°C and the effect of fall was 0.8°C. This difference was statistically significant (P < 0.001). Shivering of Grades 1 and 2 was observed in nine patients, of Group 1 while only three patients had Grades 1 and 2 shivering in Group 2. The hemodynamic parameters were similar in the two groups and did not reach significant difference.
Use of warm irrigation fluid during TURP reduces the risk of perioperative hypothermia and shivering.
PMCID: PMC4173604
Core temperature; hypothermia; irrigating fluid; spinal anesthesia; transurethral resection of prostate
16.  Effect of electroacupuncture in postanesthetic shivering during regional anesthesia: a randomized controlled trial 
Shivering during regional anesthesia is a common complication and is related to a decrease in the patient’s core body temperature. Previous studies have shown that acupuncture on specific acupoints can preserve core body temperature. The present study evaluated the effect of electroacupuncture in preventing the shivering caused by regional anesthesia.
This prospective and randomized controlled study analyzed the data from 80 patients undergoing urological surgery, who were classified as ASA I or II. Spinal anesthesia was performed in all patients using 15 mg of bupivacaine. The patients were randomly allocated to receive either placebo acupuncture (Group P, n = 40) or electroacupuncture (Group A, n = 40) for 30 min before administration of spinal anesthesia. Shivering score was recorded at 5 min intervals, with 0 representing no shivering and 4 representing the most severe shivering possible. Heart rate, blood pressure, and tympanic temperature were recorded before the intrathecal injection, and again every 5 min thereafter until 30 min.
After spinal anesthesia, the decrease in tympanic temperature was less for Group A patients than Group P, with the difference being statistically significant. After 15 min, 13 patients in Group P attained a shivering score of 3 or more, compared with 3 patients in Group A. Significantly more patients in Group P attained a shivering score of at least 1.
The prophylactic use of electroacupuncture might maintain core body temperature, and may effectively prevent the shivering that commonly develops during regional anesthesia.
Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12612000096853.
PMCID: PMC3526538  PMID: 23181618
Acupuncture; Shivering; Thermoregulation
17.  Dexamethasone for Prevention of Postoperative Shivering: A Randomized Double-Blind Comparison with Pethidine 
Postoperative shivering is very common and followed by many problems such as increasing oxygen consumption, blood pressure, intracranial and intraocular pressure, and postoperative pain. Therefore, prevention of shivering is important, especially in elderly and ischemic heart disease patients. The goal of this study was to compare the effect of pethidine (meperidine), dexamethasone, and placebo on prevention of shivering.
This double-blind clinical trial study was carried out on 120 patients who were candidates for surgery under general anesthesia. The patients were randomly divided into three groups. Induction and maintenance of anesthesia for all patients were similar. Temperature of patients was measured every 5 min interval. After induction, saline 0.9%, dexamethasone and pethidine were injected to groups a, b, and c, respectively. In recovery, patients were controlled for visible shivering. All data were statistically analyzed by analysis of variance (ANOVA) and Chi-square tests.
There were no significant differences among three mentioned groups regarding gender, age, duration of surgery and anesthesia, extubation time, duration of recovery, and basic clinical characteristics. Nineteen cases (47.5%) of placebo group had postoperative shivering, whereas in dexamethasone group only four cases (10%) had shivering and the difference between the two groups was significant. Also in pethidine group, 15 cases (37.5%) had shivering and the difference with placebo group was significant (P value = 0.001).
The present study showed that pethidine and dexamethasone are effective drugs for prevention of postoperative shivering in elective surgery and the effect of dexamethasone in preventing the postoperative shivering is better than pethidine.
PMCID: PMC3775222  PMID: 24049601
Dexamethasone; general anesthesia; shivering; surgery; pethidine
18.  Dexmedetomidine for the prevention of shivering during spinal anesthesia 
Clinics  2011;66(7):1187-1191.
The aim of this study was to evaluate the effect of dexmedetomidine on shivering during spinal anesthesia.
Sixty patients (American Society of Anesthesiologists physical status I or II, aged 18-50 years), scheduled for elective minor surgical operations under spinal anesthesia with hyperbaric bupivacaine, were enrolled. They were administered saline (group C, n = 30) or dexmedetomidine (group D, n = 30). Motor block was assessed using a Modified Bromage Scale. The presence of shivering was assessed by a blinded observer after the completion of subarachnoid drug injection.
Hypothermia was observed in 21 patients (70%) in group D and in 20 patients (66.7%) in group C (p = 0.781). Three patients (10%) in group D and 17 patients (56.7%) in group C experienced shivering (p = 0.001). The intensity of shivering was lower in group D than in group C (p = 0.001). Time from baseline to onset of shivering was 10 (5-15) min in group D and 15 (5-45) min in group C (p = 0.207).
Dexmedetomidine infusion in the perioperative period significantly reduced shivering associated with spinal anesthesia during minor surgical procedures without any major adverse effect during the perioperative period. Therefore, we conclude that dexmedetomidine infusion is an effective drug for preventing shivering and providing sedation in patients during spinal anesthesia.
PMCID: PMC3148462  PMID: 21876972
Dexmedetomidine; Shivering; Spinal anesthesia
19.  A comparative study evaluating the prophylactic efficacy of oral clonidine and tramadol for perioperative shivering in geriatric patients undergoing transurethral resection of prostate 
Background and Aims:
Perioperative shivering, in geriatric patients undergoing urological surgery under central neuraxial blockade is a common complication. Prophylactic measures to reduce shivering are quintessential to decrease the morbidity and mortality. Believing that oral formulation will bring down the cost of treatment, we decided to compare the efficacy of oral clonidine and tramadol, as premedication, in prevention of shivering in patients undergoing transurethral resection of prostate (TURP) under spinal anesthesia in a prospective and double-blind manner.
Materials and Methods:
The patients were randomly allocated into three groups (40 patients each). Group I received oral clonidine 150 μg, Group II received oral tramadol 50 mg, while Group III received a placebo. Number of patients having shivering, their grades and duration, hemodynamic changes, and side-effects in the form of sedation were recorded. Data were analyzed using analysis of variance, Student's t-test, Z test as and when appropriate.
In group I and II, 38 patients (95%) and 37 patients (92.5%) did not shiver, respectively. Although in the group III, 24 patients (60%) exhibited no grade of shivering, the shivering was of significantly severe intensity and lasted for a longer duration. No, clinically significant collateral effects were observed in patients who were administered clonidine or tramadol.
Oral clonidine and tramadol were comparable in respect to their effect in decreasing the incidence, intensity, and duration of shivering when used prophylactically in patients who underwent TURP under subarachnoid blockade.
PMCID: PMC4152672  PMID: 25190940
Clonidine; postanesthetic shivering; spinal anesthesia; tramadol; transurethral resection of prostate
20.  Reduction in the incidence of shivering with perioperative dexmedetomidine: A randomized prospective study 
Background and Aims:
Shivering is distressing to the patient and discomforting to the attending anesthesiologist, with a varying degree of success. Various drugs and regimens have been employed to abolish the occurrence of shivering. The present study aims to explore the effectiveness of dexmedetomidine in suppressing the postanesthetic shivering in patients undergoing general anesthesia.
Materials and Methods:
The present study was carried out on 80 patients, in American Society of Anesthesiologists I and II, aged 22–59 years, who underwent general anesthesia for laparoscopic surgical procedures. Patients were allocated randomly into two groups: group N (n = 40) and group D (n = 40). Group D were administered 1 μg/kg of dexmedetomidine intravenously, while group N received similar volume of saline during peri-op period. Cardiorespiratory parameters were observed and recorded during the preop, intraop, and postop periods. Any incidence of postop shivering was observed and recorded as per 4 point scale. Side effects were also observed, recorded, and treated symptomatically. Statistical analysis was carried out using statistical package for social sciences (SPSS) version 15.0 for windows and employing ANOVA and chi-square test with post-hoc comparisons with Bonferroni's correction.
The two groups were comparable regarding demographic profile (P > 0.05). Incidence of shivering in group N was 42.5%, which was statistically highly significant (P = 0.014). Heart rate and mean arterial pressure also showed significant variation clinically and statistically in group D patients during the postop period (P = 0.008 and 0.012). A high incidence of sedation (P = 0.000) and dry mouth (P = 0.000) was observed in group D, whereas the incidence of nausea and vomiting was higher in group N (P = 0.011 and 0.034).
Dexmedetomidine seems to possess antishivering properties and was found to reduce the occurrence of shivering in patients undergoing general anesthesia.
PMCID: PMC3275980  PMID: 22345953
Dexmedetomidine; hypothermia; shivering; tramadol
21.  Comparative evaluation of recovery characteristics of fentanyl and butorphanol when used as supplement to propofol anaesthesia 
Background and Aim:
Narcotics have been used since long as a component of balanced anaesthesia, thus minimizing the anaesthetic requirement both during induction and maintenance as well as attenuating the pressor response during laryngoscopy and intubation. Equally significant is their role in provision of smoother recovery period by minimizing postoperative pain. Other than pain, the factors like postoperative nausea and vomiting (PONV), shivering, sedation and respiratory depression are equally important in recovery from the effects of anaesthetic drugs. The present study aimed at comparing the postoperative recovery characterstics of fentanyl and butorphanol in patients undergoing open cholecystectomy under general anaesthesia.
Materials and Methods:
The present study configured one hundred adults patients of American Society of Anaesthesiologists (ASA) grade 1 or 2 of either sex scheduled to undergo elective open cholecystectomy and were randomly assigned to receive fentanyl (group F; n = 50) or butorphanol (group B; n = 50). Both group were premedicated with midazolam 0.04 mg/kg intravenously followed by injection fentanyl 2 mcg/kg or butorphanol 40 mcg/kg. Standard induction was done with propofol 2 mg/kg and vecuronium 0.1 mg/kg was used for intubation. Anaesthesia was maintained with propofol infusion and 67% nitrous oxide in oxygen. Intraoperative hemodynamic parameters were observed and recorded. Postoperatively analgesia, sedation, PONV, shivering, respiratory depression and recovery score were observed.
The recovery time was less in group F (P > 0.05) while post operative analgesia (P < 0.001) and sedation (P > 0.05) was more in group B. The incidence of respiratory depression was more in group B (P > 0.05). PONV was comparable in both the groups. Postoperative shivering was significantly low in group B (P < 0.05).
It is concluded that besides easy availability and lower cost, butorphanol decreased propofol consumption intraoperatively and provided better analgesia and prophylaxis against shivering in postoperative period.
PMCID: PMC3678702  PMID: 23776820
Butorphanol; fentanyl; propofol; recovery
22.  The effects of warm and cold intrathecal bupivacaine on shivering during delivery under spinal anesthesia 
Saudi Journal of Anaesthesia  2012;6(4):336-340.
Shivering associated with neuraxial anesthesia is a common problem that is uncomfortable for patients; it is of unknown ethnology and has no definite treatment.
The purpose of this study was to compare the effects of warm intrathecal bupivacaine stored at 23°C and cold intrathecal bupivacaine stored at 4°C on shivering during delivery under spinal anesthesia.
Seventy-eight parturient women scheduled for nonemergency cesarean delivery were enrolled in the study and separated into 2 groups. The standard group received 10 mg of heavy bupivacaine 0.5% stored at room temperature (23°C) plus 10 μg of fentanyl intrathecally (warm group), and the case group received 10 mg of heavy bupivacaine 0.5% stored at 4°C plus 10 μg of fentanyl intrathecally (cold group). Data collection, including sensory block level, blood pressure, core temperature, and shivering intensity, was first performed every minute for 10 min, then every 5 min for 35 min and, finally, every 10 min until the sensory level receded to L4.
There were no differences between the 2 groups in the amount of bleeding, pulse rate, oxygen saturation, neonatal Apgar, and incidence of vomiting. The incidence and intensity of shivering decreased in the warm group (P=0.002).
Warming of solutions can reduce the incidence and intensity of shivering in parturient candidates for cesarean delivery under spinal anesthesia.
PMCID: PMC3591550  PMID: 23493460
Cesarean; cold bupivacaine 0.5%; intrathecal; shivering; warm bupivacaine 0.5%
23.  Effect of preoperative warming during cesarean section under spinal anesthesia 
Korean Journal of Anesthesiology  2012;62(5):454-460.
Postoperative hypothermia and shivering is a frequent event in patients during cesarean section under spinal anesthesia. We assessed the effect of preoperative warming during cesarean delivery under spinal anesthesia for prevention of hypothermia and shivering.
Forty five patients undergoing elective cesarean section were randomly assigned to three groups. Group F received warmed intravenous fluid (40℃). Group A patients were actively warmed by forced air-warming. Group C was the control group. Forced air-warming and warmed fluid was maintained for the 15 min preceding spinal anesthesia. Core temperature (tympanic membrane) and the skin temperature of arm and thigh were measured and shivering was graded simultaneously.
The core temperature at 45 min decreased less in Groups F and A than Group C (-0.5℃ ± 0.3℃ vs -0.6℃ ± 0.4℃ vs -0.9℃ ± 0.4℃, respectively; P = 0.004). The arm temperature at 15 min and 30 min exhibited a greater increase in Group A than Group F and Group C (P = 0.001 and P = 0.012, respectively). Leg temperature increased similarly among the three groups. The incidence of shivering was significantly less in Group A and Group F than Group C (20%, 13.3%, and 53.3%, respectively; P = 0.035).
Preoperative forced air-warming and warmed fluid prevents hypothermia and shivering in patients undergoing elective cesarean delivery with spinal anesthesia.
PMCID: PMC3366313  PMID: 22679543
Cesarean section; Shivering; Spinal anesthesia; Warming
24.  Prophylactic effects of intrathecal Meperidine and intravenous Ondansetron on shivering in patients undergoing lower extremity orthopedic surgery under spinal anesthesia 
Intraoperative hypothermia is a common problem with anesthesia. Spinal anesthesia, the same as general anesthesia, affects the process of temperature regulation. The aim of this study was to compare the prophylactic effect of intravenous (IV) ondansetron with intrathecal (IT) meperidine on prevention of shivering during spinal anesthesia in patients underwent orthopedic surgery of the lower limb.
In this study, 120 patients with American Society of Anesthesiologists physical status I to II, between the ages 16 and 65 were randomized into three groups. Group O and Group M were given IV ondansetron 8 mg and IT meperidine 0.2 mg/kg, before spinal anesthesia, respectively. Group C received IV saline 0.9%. The core and ambient temperatures, the incidence and intensity of shivering, blood pressure, heart rate, and maximum level of sensory block were recorded.
Shivering was observed in 15%, 2.5%, and 37.5% of patients in Groups O, M, and C, respectively. There was a significant difference between Group O and M compared to Group C (P = 0.023 for Group O vs. Group C, P < 0.001 for Group M vs. Group C, P = 0.049 for Group M vs. Group O). Shivering incidence and intensity in Group M was significantly lower than Group O (P = 0.049 and P = 0.047, respectively). Twenty-two patients required additional IV meperidine among which 15 patients were from Group C (37.5%), six patients from Group O (15%) and one patient from Group M (2.5%).
We concluded that IT meperidine and IV ondansetron comparably can decrease intensity and incidence of shivering compared to control group as well as decreasing the requirement to additional doses of meperidine for shivering the control without any hemodynamic side effect.
PMCID: PMC4199198  PMID: 25328899
Hypothermia; Meperidine; Ondansetron; orthopedic surgery; shivering; spinal anesthesia
25.  The Effects of Preemptive Tramadol and Dexmedetomidine on Shivering During Arthroscopy 
Saudi Journal of Anaesthesia  2014;8(2):238-243.
Shivering, the rate of which in regional anesthesia is 39% is an undesired complication seen postoperatively.
This study aims to compare the ability of preventing the shivering of preemptive tramadol and dexmedetomidine during the spinal anesthesia (SA).
A total of 90 patients with American Society of Anesthesiologists physical status I-II, aged 18-60 years and undergoing elective arthroscopic surgery with SA were divided into three groups randomly. After spinal block, 100 mg tramadol in 100 ml saline was applied in group T- (n = 30) and 0.5 μg/kg dexmedetomidine in 100 ml saline was applied in group D- (n = 30) and 100 ml saline was administered in group P- (n = 30) in 10 min. The hemodynamics, oxygen saturation, tympanic temperature, shivering and sedation scores were evaluated and recorded intraoperatively and 45 min after a postoperative period.
In group T and D, shivering scores were significantly lower when compared with group P in the intraoperative 20th min (P = 0.01). Sedation scores in group D were significantly higher than the baseline values (P = 0.03) and values in group T and P (P = 0.04).
Preemptive tramadol and dexmedetomidine are effective in preventing the shivering under SA. In addition, dexmedetomidine was superior in increasing the level of sedation which is sufficient to prevent the anxiety without any adverse effects.
PMCID: PMC4024684  PMID: 24843340
Arthroscopic surgery; dexmedetomine; shivering; spinal anesthesia; tramadol

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