Intraoperative hypothermia is well known to cause various complications during both intraoperative and postoperative periods [1-3]. Much effort has been devoted to improving core temperature preservation. Because the main mechanism for the first hour of heat loss during general anesthesia is redistribution of heat from the central core to the periphery [4], many approaches have been attempted to reduce vasodilation and, by consequence, decrease core temperature loss [5]. Ephedrine stimulates norepinephrine release and also has mild β-adrenergic agonist effects, which may be able to counteract vasodilation. Its duration of action also provides the possibility for it to be administered as a bolus dose. An admixture of ephedrine and propofol had demonstrated more hemodynamic stability when administered for induction [6, 7]. Therefore, the mixture may be able to both preserve core temperature and reduce hypotension caused by propofol. This study was designed to determine the efficacy of single bolus dose of ephedrine given during induction of general anesthesia on preserving esophageal temperature.
The study was approved by Committee on Human Rights Related to Research Involving Human Subjects, Faculty of Medicine Ramathibodi Hospital, Mahidol University and protocol of this study was registered in Thai Clinical Trials Registry and coded as TCTR20141212002. We recruited 30 patients in Ramathibodi Hospital aged 18-70 years old with an American Society of Anesthesiologist physical status I–III who were scheduled to undergo plastic or breast surgery with expected duration of surgery longer than 120 min. Signed written informed consent was obtained from all patients. Patients with a tympanic temperature more than 37.5°C, blood pressure at time of induction more than 140/90 mmHg, BMI more than 30, thyroid disease, receiving medications for hypertension, with a risk of aspiration or expected difficult airway were excluded. The patients with actual surgery time less than 90 min, hand, wrist, forearm, or intraoral surgery were also excluded. The patients were randomized into an ephedrine group (n = 15) and control group (n = 15) using a computer-generated randomization list in a sealed envelope.
All patients received 7.5 mg of midazolam orally before the scheduled time for surgery. Warmed Ringer’s acetate (41°C) was used for intravenous fluid supplementation in all patients. A skin temperature probe was attached to the palmar side of index finger of the noninfused arm and index temperature was recorded. At time of induction all patients received intravenous 50 μg of fentanyl. General anesthesia was induced with a mixture of 2 mg/kg of propofol and 12 mg (6 mg/mL, total 2 mL) of ephedrine in ephedrine group and mixture of 2 mg/kg of propofol and 2 mL of normal saline in the control group. All induction agents were prepared by another anesthesiologist who was not involved in data collection and analysis. After induction patients in both groups were ventilated with 2% sevoflurane and oxygen. Atracurium 0.5 mg/kg was given and intubation was performed 3 min later. Anesthesia was maintained with 1% sevoflurane in FiO2 0.5 oxygen/nitrous oxide during study and depended on attending anesthesiologist thereafter. Additional doses of fentanyl, atracurium, and rate of Ringer’s acetate infusion were also at the discretion of the attending anesthesiologist. Before intubation, tympanic temperature, index temperature, blood pressure were recorded preinduction (Pre-in) and at 2.5 min after induction (Post-in). Immediately after intubation (T0), an esophageal temperature probe was installed and esophageal temperature, tympanic temperature, index temperature, and blood pressure were recorded. After intubation esophageal temperature, index temperature, and blood pressure were recorded at 15 min intervals (T0, T1, …, T120). If during the study, systolic blood pressure fell below 90 mmHg then 300 mL of Ringer’s acetate would be loaded and 2.5 min later blood pressure would be remeasured. If systolic blood pressure remained below 90 mmHg, the patient would be recorded as having hypotension. Then 3 mg of ephedrine would be given and blood pressure would be remeasured at every 2.5 min until systolic blood pressure rose higher than 90 mmHg. If esophageal temperature fell below 35°C, the patient would be warmed using a forced-air warmer. If ephedrine was given because of hypotension or a forced-air warmer was applied, data collected subsequently would not be analyzed. At 90 min and 120 min after intubation, the amount of intravenous fluid infused, blood loss, total fentanyl, and ephedrine given were recorded. Data collection ceased at 120 min after intubation or after skin suturing was completed. The attending anesthesiologist collected all data. The primary outcome was to demonstrate a difference in esophageal temperature between the groups.
Based on a previous study [8], sample size was calculated with an α error of 0.5 and power of 80%. A sample size power calculation determined that 12 patients were needed in each group. A further 20% of participants were added for dropout, resulted in 15 patient participants per group and total of 30 participants.
All results were analyzed using IBM SPSS Statistics for Windows (version 20.0, IBM Corp, Armonk, NY, USA). According to the results from a Shapiro–Wilk normality test, parametric data (e.g. age, body weight, height, all measured temperatures) were summarized by mean and standard deviation, where nonparametric data (e.g. blood loss and anesthesia time) by median and range, and categorical data by number with percentage. Parametric and nonparametric data were compared using a
All demographic and perioperative data are shown in
From after induction to the immediate postintubation period, tympanic membrane temperature did not change significantly from baseline at preinduction in either group. After intubation esophageal temperature gradually declined in both groups and became significant when compared with immediate post-intubation (T0) after T15 for control group, and T30 for ephedrine group. When compared between groups, esophageal temperature was significantly higher in the ephedrine group start from T60 to T90. Index temperature, when compared between groups, was significantly higher in the ephedrine group only at post-induction 2.5 min and T0. The index temperature was highest at T15 in the ephedrine group and at T30 in control group (
After induction systolic blood pressure in the ephedrine group tended to rise and became significantly higher at T0 then significantly fell to below preinduction from T15 to T30. In control group, systolic blood pressure was significantly lower than preinduction at 2.5 min after induction, from T15 to T45, and at T75. When compared between groups, significant differences in systolic blood pressure were found from 2.5 min after induction to T15. Diastolic blood pressure also showed similar pattern (
Patient characteristics and preoperative data
Control (n = 15) | Ephedrine (n = 15) | ||
---|---|---|---|
Sex, female/male, n | 11/4 | 12/3 | >0.999 |
Age, y | 33.8 ± 11.3 | 30.3 ± 9 . 9 | 0.38 |
BMI | 21.9 ± 3.2 | 21.8 ± 3 . 8 | 0.87 |
Operating room temperature, °C | 21.1 ± 0.9 | 20.8 ± 1 . 2 | 0.42 |
Anesthesia time, min (median [range]) | 145 [95-290] | 135 [90-405] | 0.39 |
At 90 min | |||
Hypotension, n | 0 | 0 | – |
IV fluid, mL | 963 ± 418 | 660 ± 219 | 0.02 |
Blood loss, mL (median [range]) | 20 [5-500] | 4 0 [5-250] | 0.41 |
Fentanyl, μg (median [range]) | 100 [50-250] | 100 [50-150] | 0.38 |
At 120 min | |||
Hypotension, n | 1 | 0 | >0.999 |
IV fluid, mL | 1235 ± 578 (n = 11) | 762 ± 245 (n = 11) | 0.02 |
Blood loss, mL (median [range]) | 20 [5-500] (n = 11) | 50 [5–250] (n = 11) | 0.52 |
Fentanyl, μg (median [range]) | 100 [50–300] (n = 11) | 100 [50–150] (n = 11) | 0.22 |
Values are the mean ± SD, unless specified
Comparing temperature between groups
Temperature | Control (n = 15) | Ephedrine (n = 15) | Temperature | Control (n = 15) | Ephedrine (n = 15) | ||
---|---|---|---|---|---|---|---|
Tympanic | 0.38 | Index | 0.03 | ||||
Pre-in | 36.6 ± 0.45 | 36.7 ± 0 . 5 | 0.55 | Pre-in | 26.7 ± 2.1 | 27.99 ± 2.49 | 0.15 |
Post-in | 36.4 ± 0.42 | 36.7 ± 0 . 5 | 0.099 | Post-in | 27.9 ± 2.6 | 30.53 ± 2.55 | 0.01 |
T0 | 36.4 ± 0.7 | 36.5 ± 0 . 5 | 0.83 | ||||
Esophageal | 0.03 | T0 | 29.7 ± 2.8 | 31.96 ± 2.52 | 0.03 | ||
T0 | 36.3 ± 0.3 | 36.4 ± 0 . 4 | 0.51 | ||||
T15 | 35.9 ± 0.4 | 36.2 ± 0.4 | 0.13 | T15 | 32.7 ± 1.7 | 33.31 ± 2.45 | 0.47 |
T30 | 35.8 ± 0.5 | 36.0 ± 0 . 4 | 0.11 | T30 | 33.0 ± 1.8 | 33.05 ± 1.89 | 0.97 |
T45 | 35.7 ± 0.4 | 35.9 ± 0 . 4 | 0.09 | T45 | 32.3 ± 2.6 | 32.80 ± 1.70 | 0.49 |
T60 | 35.5 ± 0.4 | 35.9 ± 0.4 | 0.02 | T60 | 30.5 ± 3.8 | 32.49 ± 2.19 | 0.06 |
T75 | 35.5 ± 0.4 | 35.9 ± 0.4 | 0.01 | T75 | 29.8 ± 4.1 | 31.60 ± 2.48 | 0.16 |
T90 | 35.4 ± 0.4 | 35.9 ± 0.4 | 0.006 | T90 | 28.8 ± 4.3 | 31.13 ± 2.90 | 0.09 |
T105 | 35.6 ± 0.4 (n = 8) | 35.9 ± 0.5 (n = 11) | T105 | 29.3 ± 3.5 | 31.78 ± 3.29 (n = 11) | ||
T120 | 35.6 ± 0.4 (n = 8) | 35.9 ± 0 . 6 (n = 11) | T120 | 29.7 ± 4.3 (n = 8) | 32.62 ± 2.21 (n = 11) |
Values are the mean ± SD
Comparing systolic and diastolic blood pressure between groups
Systolic pressure | Control (n = 15) | Ephedrine (n = 15) | Diastolic pressure | Control (n = 15) | Ephedrine (n = 15) | ||
---|---|---|---|---|---|---|---|
0.006 | 0.046 | ||||||
Pre-in | 120.4 ± 16.1 | 120.9 ± 13.5 | 0.92 | Pre-in | 72.9 ± 7.6 | 75.4 ± 11.7 | 0.49 |
Post-in | 91.0 ± 10.6 | 125.5 ± 14.5 | <0.001 | Post-in | 51.1 ± 8.4 | 73.3 ± 12.7 | <0.001 |
T0 | 121.1 ± 19.9 | 142.5 ± 25.9 | 0.02 | T0 | 78.9 ± 16.7 | 85.6 ± 17.7 | 0.30 |
T15 | 97.0 ± 10.0 | 111.0 ± 11.7 | 0.001 | T15 | 59.5 ± 9.2 | 65.5 ± 14.7 | 0.19 |
T30 | 104.4 ± 15.4 | 109.5 ± 10.7 | 0.30 | T30 | 68.1 ± 12.4 | 63.7 ± 10.8 | 0.30 |
T45 | 107.7 ± 15.2 | 113.7 ± 15.9 | 0.30 | T45 | 70.2 ± 15.4 | 67.1 ± 10.5 | 0.53 |
T60 | 109.9 ± 12.3 | 113.01 ± 12.5 | 0.49 | T60 | 70.3 ± 14.5 | 69.1 ± 12.6 | 0.81 |
T75 | 108.3 ± 12.5 | 120.5 ± 19.2 | 0.048 | T75 | 70.6 ± 12.1 | 73.2 ± 12.4 | 0.45 |
T90 | 113.2 ± 15.4 | 118.6 ± 12.1 | 0.30 | T90 | 72.7 ± 15.3 | 70.3 ± 13.7 | 0.65 |
T105 | 114.5 ± 16.6 | 114.9 ± 13.0 | T105 | 74.9 ± 11.7 | 67.6 ± 10.7 | ||
(n = 10) | (n = 11) | (n = 10) | (n = 11) | ||||
T120 | 118.0 ± 14.6 | 112.9 ± 11.8 | T120 | 76.3 ± 14.6 | 66.5 ± 12.5 | ||
(n = 10) | (n = 11) | (n = 10) | (n = 11) |
Values are the mean ± SD
Systolic blood pressure and diastolic blood pressure by group. Open circles indicate the ephedrine group, and solid circles indicate the control group. Data are mean with standard error of mean,
Index temperature by group. Open circles indicate the ephedrine group, and solid circles indicate the control group. Data are mean with standard error of mean, *
Tympanic and esophageal temperature by group. Tympanic temperatures are represented by circles and esophageal temperatures are represented by triangles. Open symbols indicate the ephedrine group, and solid symbols indicate the control group. Data are mean with standard error of mean,
The current study suggested that ephedrine administered as bolus dose during induction is effective in preventing core temperature loss in plastic and breast surgery. The mixture of 12 mg of ephedrine and 2 mg/kg of propofol used results in a mild increase in blood pressure after induction, which was only significant immediately after intubation, and then fell below baseline to a lesser degree when compared with a mixture of propofol and normal saline.
Previously, successful treatment of cyclical hypothermia with ephedrine had been reported [9]. Jo et al. also reported the core temperature conserving property of ephedrine when infused continuously after intubation in spine surgery with no significant hypertension [8].
The increase in index temperature after induction in both groups suggested the effect of heat redistribution. Faster time-to-peak in the ephedrine group suggests an increase in cardiac output while the early decline suggests a vasoconstriction effect. Both esophageal and index temperature tended to be higher in the ephedrine group. This might be partly result from increasing metabolism or from the β-adrenergic agonist effect of ephedrine [10].
More stable hemodynamics have been reported for combined ephedrine with propofol. Less hypotension with no significant hypertension was found when 0.15 mg/kg ephedrine was combined with 2.5 mg/kg of propofol, and 3 μg/kg of remifentanil [7]. A similar profile can be seen in this study except for the significant increase in blood pressure at immediate after intubation, which might result from the difference in anesthetic agents and doses.
Some of limitations of this study should be considered. An esophageal temperature probe was not fitted before intubation because of patient discomfort. By using tympanic membrane temperature, the trend of core temperature change can be demonstrated, but may not be a reliable substitute for baseline. The amount of fluid infused was determined by the attending anesthesiologist. Therefore, all fluid was warmed to 41°C to minimize the effect of cold fluid. Finally, plastic surgery varies in sites of operation and exposures may affect heat loss and skin temperature monitoring.
Induction of general anesthesia with mixture of ephedrine and propofol can decrease core temperature loss during plastic and breast surgery compared with propofol alone.