Comparison of the Effects of Etomidate and Propofol on Redistribution Hypothermia During General Anesthesia

대한마취과학회지 2006; 50: S 19∼24 □ 영문논문 □ Korean J Anesthesiol Vol. 50, No. 6, June, 2006

Comparison of the Effects of Etomidate and Propofol on Redistribution Hypothermia during General Anesthesia

Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam; *Kyung Hee East-West Neo Medical Center; †Seoul National University Hospital, Seoul, Korea

Hee-Pyoung Park, M.D., Jong-Man Kang, M.D.*, Young-Tae Jeon, M.D., In-Yong Choi, M.D.†, Yong-Seok Oh, M.D., and Jung-won Hwang, M.D.

Background: Redistribution hypothermia can be modified by the effects of induction anesthesia on the systemic vascular resistance. This study compared the effects of etomidate and propofol on redistribution hypothermia during general anesthesia. Methods: Forty patients were randomly allocated into one of two groups, based on the induction agent used: Group E (n = 20) received 0.2 mg/kg of etomidate and group P (n = 20) received 2.5 mg/kg propofol. After intubation, anesthesia was maintained with sevoflurane and 50% nitrous oxide in oxygen in both groups. The core and peripheral temperatures were measured, and the peripheral temperature gradients (forearm minus fingertip) were used as an index of an arteriovenous shunt. Results: The patients in both groups demonstrated intense vasoconstriction prior to the induction of anesthesia with similar skin-temperature gradients. After induction, group P showed more rapid and significant vasodilation than group E (P = 0.02). The difference in vasodilation between the two groups disappeared from 5 minutes after intubation. The pre-induction core temperatures were similar in both groups. After induction, the core temperatures in group P were consistently lower than those in group E (P ＜ 0.01). The core temperatures during the first hour of anesthesia decreased by 1.5 ± 0.4oC in group P but only by 0.9 ± 0.4oC in group E. Conclusions: Propofol caused more rapid and aggravated redistribution hypothermia during surgery than etomidate due to the earlier arteriovenous shunt vasodilation. (Korean J Anesthesiol 2006; 50: S 19∼24) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ Key Words: etomidate, general anesthesia, propofol, redistribution hypothermia.

Once redistribution of body heat occurred, the heat which INTRODUCTION had escaped to the peripheral tissues could not be recovered by the core, as heat does not move up a temperature Redistribution hypothermia is an internal core-to-peripheral gradient. In the early period of anesthesia, alterations in core redistribution of body heat during the first hour after the temperatures due to difference in systemic vascular resistance induction of general anesthesia. It is associated with several (SVR) of induction agents can affect the ultimate severity of adverse clinical outcomes, including postoperative shivering,1) redistribution hypothermia occurred during the first hour after increased blood loss,2) decreased drug metabolism and clear- the anesthetic induction.12,13) ance,3) morbid myocardial outcomes,4) wound infection,5) and A major difference between etomidate and propofol has delayed recovery from anesthesia.6) Redistribution hypothermia been observed in their impact on vasomotor tone. Etomidate results from anesthetic-induced central inhibition of tonic ther- results in a minimal degree of reduction in SVR, but propofol moregulatory vasoconstriction in the arteriovenous shunt7-9) and induces a severe drop in SVR.14,15) Accordingly, we tested the anesthetic-induced arterial and venous vasodilation.10,11) hypothesis that etomidate as an induction agent result in less redistribution hypothermia than propofol. Received : April 20, 2006 Corresponding to : Jung-won Hwang, Department of Anesthesiology and MATERIALS AND METHODS Pain Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-Gu, Seongnam-si, Gyeonggi-do 463-500, Korea. Tel: 82-31-787-7492, Fax: 82-31-787-4063, E-mail: [email protected] Subsequent to approval from the Local Committees and the

S 19 Korean J Anesthesiol：Vol. 50. No. 6, 2006 acquisition of written informed consent, we studied 40 ASA justed to approximately 4 ml/kg/hr. The patients were covered physical status I-II patients undergoing laparoscopic chole- with a single surgical drape of synthetic cloth except right fore- cystectomy under general anesthesia. Obese patients, patients arm and hand, which were left exposed throughout the proce- with thyroid or otologic disease, dysautonomia or Raynaud's dure. No active warming systems were employed during the syndrome, those receiving vasodilating drugs, those in which study period. Surgery began at 15-20 minutes after intubation. the laparoscopic procedure was converted to an open chole- In this study, total 3 anesthesiologists were enrolled. At cystectomy and those receiving vasoconstrictors during anes- anesthetic induction, propofol or etomidate was administrated thetic induction were excluded from this study. to patients by only one anesthesiologist who knew the induc- Upon patients' arrivals at the reception room, their tympanic tion agent. Other two anesthesiologists (data-collecting person- temperatures were taken with Thermoscan Plus Thermometer nel) without knowledge of the induction agent recorded core (Braun, Kronberg, Germany), in which accuracy provided by and peripheral temperatures in 40 patients equally. The pe- the manufacturer was ± 0.2oC. Mean value of triple-checked ripheral temperatures were recorded before induction and every tympanic temperatures was recorded as the initial core tem- minute after induction until inhalation agent or other drug perature baseline measurement. None of the patients who had administered. After intubation, the core and peripheral tem- been enrolled in this study received any premedication. Prior peratures were measured every 5 minutes for one hour. Heart to the induction of anesthesia, mean blood pressure and heart rate, mean blood pressure and sevoflurane concentrations were rate were checked and the patients' peripheral temperatures monitored every 5 minutes throughout the study. were measured on the palmar side of the right index finger Skin-surface temperature gradients (forearm minus fingertip and lower arm. Skin surface thermometer probes (HP 21078A, temperature gradients) were used as an index of hand arterio- Palo Alto, CA, USA), in which accuracy by our measurement venous shunt perfusion. As in previous studies,17) we consid- were ± 0.1oC, were placed on the fingertip and midway ered a gradient below 0oC to indicate vasodilation. between the wrist and elbow on the radial aspect of the A pilot study of 20 patients revealed that the standard forearm. The room temperature and humidity in the operating deviation in core temperature taken 15 minutes after intubation room were also measured. was 0.43oC. In order to demonstrate a 0.4oC difference in 40 patients were randomly assigned to one of two groups mean core temperature between two groups as significant at based on the induction agent using a sealed envelope method the 0.05 level with a power of ＞ 80%, we calculated that and a random-number table. Group E patients (n = 20) re- the study required a minimum of 20 patients per group. ceived 0.2 mg/kg of etomidate and Group P patients (n = 20) Results are expressed as means unless otherwise stated. Demo- received 2.5 mg/kg of propofol. After confirming patients' graphic and anesthetic data were compared using independent unconsciousness, an esophageal temperature probe (Deroyal, T-tests and chi-squared test, as appropriate. Continuous variables Powell, TN, USA) was inserted in accordance with the tech- including core temperature, skin temperature gradients, heart nique described by Kaufman for intraoperative core temper- rate, sevoflurane concentration and mean blood pressure were ature measurement,16) in which accuracy provided by the man- analyzed with repeated measures of ANOVA. A P value of ＜ ufacturer was ± 0.2oC, Rocuronium (0.6 mg/kg) was used to 0.05 was considered to be statistically significant. facilitate endotracheal intubation. The trachea was intubated approximately 4 minutes after induction. After intubation, anes- RESULTS thesia was maintained using 1-4 vol% end-tidal sevoflurane and intermittent injections of alfentanil (5μg/kg). The end- The demographic data were similar between the two groups, tidal PaCO2 was maintained at approximately 35 mmHg. Fresh including ambient temperature and humidity in the operating gas flows of oxygen (1 L/min) and N2O (1 L/min) were room, as well as the volume of fluid administered throughout administered using a semi-closed circular system without air- the study period (Table 1). way heating or humidification. Hartman solution, kept at room Pre-induction core temperatures were similar in the two temperature, was administrated to both group patients by full groups. After induction, there was significant difference in dripping from administration of induction agents until tracheal core temperature between groups (P ＜ 0.01, Fig. 1). Core intubation. After that time, administrated fluid volume was ad- temperatures in the patients receiving propofol were signifi-

S 20 Hee-Pyoung Park, et al : Etomidate vs Propofol on Hypothermia

Table 1. Demographic and Anesthetic Data ꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚꠚ Group E Group P (n = 20) (n = 20) ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ Age (yr) 52 ± 7 50 ± 8 Gender (M/F) 10/10 9/11 Height (cm) 162 ± 7 161 ± 8 Weight (kg) 63 ± 7 60 ± 8 Ambient temperature in 21.8 ± 0.6 21.9 ± 0.5 operation room (oC) Humidity in operation room (%) 57 ± 1 57 ± 2 Operation time (min) 78 ± 20 76 ± 18 Total intravenous fluid (ml) 455 ± 146 478 ± 153 Total number of patients received alfentanil/ 3/1000 2/600 total dose of alfentanil used (μg) Fig. 2. The change of forearm-fingertip temperature gradients after ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ induction but before administration of sevoflurane or alfentanil. A Data are presented as mean ± SD. There are no differences in gradient value below 0oC indicates vasodilation. There is significant demographic and anesthetic data between groups. Group E: received difference in decrease of temperature gradients between groups (P = etomidate 0.2 mg/kg as induction agent, Group P: received propofol 0.02). *: P ＜ 0.05 vs before induction in each group. Group E: 2.5 mg/kg as induction agent. Total intravenous fluid represents total received etomidate 0.2 mg/kg as an induction agent, Group P: received volume of fluid administrated during one hour of anesthesia. propofol 2.5 mg/kg as an induction agent.

Fig. 1. Time course of core temperature. There is significant difference in temperature between groups (P ＜ 0.01). Core temperature decreases more rapidly and severely in group P than in group E. *: P ＜ 0.01 vs value at baseline in each group. Group E: received etomidate 0.2 mg/kg as an induction agent, Group P: received propofol 2.5 mg/kg as an induction agent. Base: baseline, Intu: intubation. cantly lower than those in the patients receiving etomidate (P already showed vasodilation 2 minutes after injection. In con- ＜ 0.01). One hour after intubation, core temperatures de- trast, the patients receiving etomidate remained vasoconstricted creased from baseline by 1.5 ± 0.4oC in group P but only 4 minutes after injection. The patients in both groups kept 0.9 ± 0.4oC in group E. After intubation, core temperatures similarly vasodilated from 5 minutes after intubation and were significantly different from baseline values in group P, thereafter (Fig. 3). whereas 10 minutes after intubation, core temperatures were There was no significant difference in mean blood pressure, significantly different in group E (P ＜ 0.01). heart rates and sevoflurane concentration between two groups The patients in both groups demonstrated intense vasocon- (Fig. 4). striction before induction of anesthesia with similar skin-temperature gradients (forearm minus fingertip). The gradients de- DISCUSSION creased quickly more after propofol administration than after etomidate (P ＜ 0.05, Fig. 2). The patients receiving propofol This study show that core temperature decreased significantly

S 21 Korean J Anesthesiol：Vol. 50. No. 6, 2006 more after induction with propofol than with etomidate and hypothermia observed in group P, compared to group E, is that hypothermia persisted for the duration of surgery. that the drug induced a brief period of systemic vasodilation The most likely explanation for the rapid and exaggerated which facilitated the core-to-peripheral redistribution of body heat in early period of anesthesia, such as anesthetic induction. Once redistribution occurred, the heat which had escaped to the peripheral tissues could not be recovered by the core, as the transfer of heat is normally from a high temperature part (core of body) to a lower temperature part (periphery of body).12) Moreover, because anesthesia after intubation was maintained with sevoflurane and nitrous oxide in all patients and there were no significant differences in sevoflurane concentrations and total dose of alfentanil used between the groups, the observed temperature differences presumably result exclusively from the choice of induction drug applied. This study demonstrates that immediately after intubation (approximately 4 minutes after induction but before inhaled sevoflurane administration), core temperature remarkably de- Fig. 3. Time course of forearm-fingertip temperature gradients during creased from preinduction value by 0.5oC in group P and that o operation. A gradient value below 0 C indicates vasodilation. After the core temperature in group P was significantly lower than intubation, there is no difference in temperature gradients between groups. Group E: received etomidate 0.2 mg/kg as an induction agent, Group P: that in group E at that time. Because of difference in time received propofol 2.5 mg/kg as an induction agent, Intu: intubation. intervals measured, such finding has not been reported in

Fig. 4. Time course of heart rate, mean blood pressure and sevoflurane concentration used. There are no differences in heart rate, mean blood pressure and sevoflurane concentration used between groups. Group E: received etomidate 0.2 mg/kg as an induction agent, Group P: received propofol 2.5 mg/kg as an induction agent. Base: baseline, Ind: induction, Intu: intubation. S 22 Hee-Pyoung Park, et al : Etomidate vs Propofol on Hypothermia previous similar studies in which core temperature in patients observing changes in mean blood pressure. We regarded that receiving propofol as induction agent was different from core although statistically not significant, the decrease in mean temperature in those receiving ketamine or inhaled sevoflurane blood pressure in group P, compared to group E, in the early at least 15 minutes after induction.12,13) As a result, we insist period of anesthesia reflects greater systemic vasodilation in that the decrease in core temperature in the patients receiving group P. We used two different sources (tympanic membrane propofol can occur earlier than 15 minutes after induction and and esophagus) for core temperature in this study because we thereby, difference in core temperature between group P and did not measure esophageal temperature as baseline value in group E can occur earlier than the time reported in previous awake patient due to ethical concern. Two different sources studies. This study also demonstrates that forearm minus for core temperature were used in a previous study.13) Al- fingertip temperature gradients decreased from preinduction though tympanic temperature is about 0.1oC lower than value one minute after propofol injection in group P, but 3 esophageal temperature, these two temperatures can be used minutes after etomidate injection in group E. In addtion, inter-changeably in the clinical setting.22) Fluid temperature and vasodilation occurred two minutes after injection in group P, the administered amount can affect body temperature. It is but 5 minutes after intubation (approximately 9 minutes after ideal to use fluid in which its temperature is the same as etomidate injection) in group E. In other words, group P body temperature. In this study, fluid kept at room temper- showed immediate vasodilation after injection, whereas group ature was excessively administrated to all patients during E showed relatively slow-onset vasodilation. Based on our anesthetic induction. However, in clinical setting, excessive result, we think that such difference in arteriovenous vaso- fluid administration is necessary to avoid hypotension during motor status between propofol and etomidate has great influ- anesthetic induction. Moreover, warmed fluid is not routinely ence on the extent of alterations in core temperatures in the used. early period of anesthesia. This study demonstrates that even a brief period of In clinical setting, additive administration of opioid and/or propofol-induced vasodilation immediately after anesthetic in- vasodilator with induction agent is often used to prevent induction can induce substantial redistribution hypothermia, which creased hemodynamic response due to intubation. We also think persists more than one hour. In conclusion, etomidate is a that such drug having a vasodilating characteristic can aggravate more useful induction agent for decreasing intraoperative redis- redistribution hypothermia in the early period of anesthesia. tribution hypothermia compared to propofol. But, further data collection should be needed to verify it. Caution is warranted in the interpretation of the decreases in REFERENCES core temperatures and forearm-fingertip temperature gradients by induction agents in this study. Temperatures can be af- 1. Eberhart LH, Doderlein F, Eisenhardt G, Kranke P, Sessler DI, Torossian A, et al: Independent risk factors for postoperative fected by noxious stimulus such as endotracheal intubation shivering. Anesth Analg 2005; 101: 1849-57. which may augment shunt tone because painful stimulation 2. Hofer CK, Worn M, Tavakoli R, Sander L, Maloigne M, Klaghofer 18) slightly increases the vasoconstriction threshold. 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