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      Clinical study of etomidate emulsion combined with remifentanil in general anesthesia

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          Abstract

          Background

          The aim of this study was to investigate and evaluate the safety, recovery time, and side effects of general anesthesia with different doses of etomidate emulsion combined with remifentanil.

          Methods

          One hundred ten patients of American Society of Anesthesiologists class 1 or 2 who underwent gynecological general anesthesia with a 1–3-hour operation time were randomly divided into the following groups: etomidate emulsion group 1 ([E1] n = 30); etomidate emulsion group 2 ([E2] n = 30); etomidate emulsion group 3 ([E3] n = 20); and propofol group ([P group] n = 30). For induction of anesthesia, 0.3 mg/kg etomidate emulsion, and the continuous remifentanil infusion also to induce anesthesia (0.1~0.3 μg · kg −1 · min −1), was applied in all cases. Afterwards, continuous infusion of etomidate emulsion and remifentanil, respectively (E1: 10 μg · kg −1 · min −1 and 0.1 μg · kg −1 · min −1; E2: 15 μg · kg −1 · min −1 and 0.2 μg · kg −1 · min −1; E3: 20 μg · kg −1 · min −1 and 0.2 μg · kg −1 · min −1), and propofol (P group: 6~10 mg · kg −1 · h −1) were administered. Changes in blood flow kinetics and adverse reactions were noted and compared between the four groups.

          Results

          Both arterial blood pressure (BP) and heart rate (HR) decreased after induction of anesthesia ( P < 0.05). Systolic (SBP) and diastolic (DBP) BP changed only slightly, and HRs were slightly infected in E1, E2, and E3. SBP, DBP, and HR during the operation all decreased significantly in P group ( P < 0.05). Muscle tremor at the time of induction occurred in 13 cases (11.8%). Following etomidate emulsion anesthesia maintenance, postoperative agitation occurred in seven cases (8.75%), lethargy in 20 cases (25%), and vomiting in 19 cases (23.75%). No adverse reactions were found in P group.

          Conclusion

          Continuous infusion of etomidate emulsion at 10 μg · kg −1 · minute −1 combined with remifentanil during anesthesia has the advantages of hemodynamic stability, quick wake-up, and few adverse reactions. Increasing the dose of etomidate emulsion increases the incidence of adverse reactions.

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          Most cited references 27

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          Reducing myoclonus after etomidate.

          The authors hypothesized that myoclonus after etomidate is dose-related, could be suppressed when small doses of etomidate were administered before induction, and is unassociated with seizure-like activity on electroencephalogram (EEG). Three studies were performed. In the first study, 36 men were randomly assigned to receive 0.025, 0.050, 0.075, 0.100, 0.200, or 0.300 mg/kg of etomidate. In a second crossover study, eight men were randomly allocated to receive either a pretreatment dose of 0.050 mg/kg etomidate or placebo 50 s before 0.300 mg/kg etomidate was injected. EEG was recorded for subjects in the first two studies. In a third study, 60 patients were randomly allocated to one of three pretreatment doses of etomidate: 0.030, 0.050, or 0.075 mg/kg before 0.300 mg/kg was given. In Study 1, myoclonus was not observed after 0.025 or 0.050 mg/kg etomidate. One volunteer had myoclonus after 0.075 mg/kg and another after 0.100 mg/kg etomidate; three had myoclonus after 0.200 mg/kg; and five after 0.300 mg/kg. Incidence of myoclonus was dose-related (P < or = 0.01). In Study 2, two volunteers (25%) with etomidate pretreatment had mild myoclonus compared to six (75%) with placebo pretreatment (P < or = 0.05). EEG changes, other than delta waves, were not seen during myoclonic epochs. In Study 3, myoclonus was less likely after the small pretreatment doses (0.030 or 0.050 mg/kg) than after the large dose (0.075 mg/kg, P < or = 0.01). Incidence and intensity of myoclonus after induction with etomidate are dose-related, suppressed by pretreatment, and unassociated with seizure-like EEG activity.
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            Adrenal suppression following a single dose of etomidate for rapid sequence induction: a prospective randomized study.

            The administration of etomidate for rapid sequence induction (RSI) has been linked to subsequent adrenocortical insufficiency in nontrauma patients. However, etomidate-related adrenocortical insufficiency has not been well studied in the trauma population. We performed a prospective, randomized, controlled study to assess the effect of one dose of etomidate for RSI on adrenal function and its clinical significance during and after resuscitation in trauma patients. Adult trauma patients admitted to our Level I trauma center requiring RSI were randomized to receive etomidate 0.3 mg/kg and succinylcholine 1 mg/kg (E group) or fentanyl 100 microg, midazolam 5 mg, and succinylcholine 1 mg/kg (FM group) for induction. A baseline serum cortisol level was drawn before RSI. Four to six hours after RSI, a postintubation serum cortisol level was drawn. An ACTH stimulation test was performed. Thirty patients were enrolled: 18 E group patients and 12 FM group patients. No statistical difference was detected between the two groups with respect to age, injury severity score, and baseline serum cortisol. Mean serum cortisol levels were significantly lower in E group patients than in FM group patients 4 to 6 hours after intubation (18.2 vs. 27.8 mug/dL, p < 0.05). Change in serum cortisol between baseline and postintubation levels was different (-12.8 mg/dL +/- 9.6 microg/dL vs. 1.1 microg/dL +/- 7.6 microg/dL, p < 0.01). Patients in the E group had an average increase in cortisol after ACTH administration of 4.2 microg/dL +/- 4.9 microg/dL vs. 11.2 microg/dL +/- 6.1 microg/dL in the FM group, p < 0.001. Patients in the E group required longer ICU lengths of stay (mean, 6.3 days vs. 1.5 days, p < 0.05), more ventilator days (mean, 28 days vs. 17 days, p < 0.01), and longer hospital lengths of stay (mean, 11.6 days vs. 6.4 days, p < 0.01). The use of etomidate for RSI in trauma patients led to chemical evidence of adrenocortical insufficiency and may have contributed to increased hospital and ICU lengths of stay and increased ventilator days. Further studies should be considered to evaluate the safety profile of this drug in trauma patients.
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              Etomidate is associated with mortality and adrenal insufficiency in sepsis: a meta-analysis*.

              To evaluate the effects of single-dose etomidate on the adrenal axis and mortality in patients with severe sepsis and septic shock. A systematic review of randomized controlled trials and observational studies with meta-analysis. Literature search of EMBASE, Medline, Cochrane Database, and Evidence-Based Medical Reviews. Sepsis patients who received etomidate for rapid sequence intubation. None. We conducted a systematic review of randomized controlled trials and observational studies with meta-analysis assessing the effects of etomidate on adrenal insufficiency and all-cause mortality published between January 1950 and February 2012. We only examined studies including septic patients. All-cause mortality served as our primary end point, whereas the prevalence of adrenal insufficiency was our secondary end point. Adrenal insufficiency was determined using a cosyntropin stimulation test in all studies. We used a random effects model for analysis; heterogeneity was assessed with the I statistic. Publication bias was evaluated with Begg's test. Five studies were identified that assessed mortality in those who received etomidate. A total of 865 subjects were included. Subjects who received etomidate were more likely to die (pooled relative risk 1.20; 95% confidence interval 1.02-1.42; Q statistic, 4.20; I2 statistic, 4.9%). Seven studies addressed the development of adrenal suppression associated with the administration of etomidate; 1,303 subjects were included. Etomidate administration increased the likelihood of developing adrenal insufficiency (pooled relative risk 1.33; 95% confidence interval 1.22-1.46; Q statistic, 10.7; I2 statistic, 43.9%). Administration of etomidate for rapid sequence intubation is associated with higher rates of adrenal insufficiency and mortality in patients with sepsis.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2013
                20 August 2013
                : 7
                : 771-776
                Affiliations
                Department of Anesthesiology, Mindong Hospital affiliated to Fujian Medical University, Fuan, Fujian, People’s Republic of China
                Author notes
                Correspondence: Digui Weng Department of Anesthesiology, Mindong Hospital Affiliated to Fujian Medical University, Fuan, Fujian, 355000, People’s Republic of China, Tel/Fax +86 137 0693 0791, Email wdgmdyy813@ 123456163.com
                Article
                dddt-7-771
                10.2147/DDDT.S45979
                3753064
                23990706
                © 2013 Weng et al. This work is published by Dove Medical Press Ltd, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Ltd, provided the work is properly attributed.

                Categories
                Rapid Communication

                Pharmacology & Pharmaceutical medicine

                general anesthesia, etomidate emulsion, remifentanil

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