Effects of Etomidate on Postoperative Circadian Rhythm Changes of Salivary Cortisol in Children

Study Overview
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Brief Summary
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Etomidate is an unique drug used for induction of general anesthesia and sedation. Adrenal cortical inhibition by etomidate has received much attention. However wether the circadian rhythm and pulse secretion pattern of cortisol in children are the same as that in adults is not known. Moreover, the effect of etomidate on circadian rhythm changes and clinical outcomes has never been carefully studied in children undergoing surgery. Our hypothesis is that etomidate can relieve the changes of circadian rhythm of salivary cortisol in children for 24-48 hours，and this does not make clinical outcomes worse postoperatively.

Detailed Description
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Sample size assessment: Using formula to calculate the total number is 30. Statistical analysis: ANOVA Reporting for adverse events: During the period of study, if there is any severe adverse event happening, such as severe infection, severe low cortisol concentration threatening the patient's life we will stop the trial.

Official Title
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Phase 1 Study of Circadian Rhythm of Salivary Cortisol in Health Children ;Phase 2 Study of Circadian Rhythm of Salivary Cortisol of Children Undergoing Surgery Using Etomidate or Not Using Etomidate.

Conditions
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Congenital Hydronephrosis, Congenital Choledochal Cyst, Fracture

Intervention / Treatment
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* Drug: etomidate
* Drug: midazolam
* Drug: propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 3-12 years old who are plan to undergo surgery Exclusion Criteria: endocrine disease, blood infusion, having fever, ulcer or bleeding in the oral cavity

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: etomidate & midazolam<br>a bolus of midazolam(Jiangsu Enhua Pharmaceutical Ltd.) 0.1mg/kg then a bolus of etomidate(Etomidate Fat Emulsion Injection, Jiangsu Enhua Pharmaceutical Ltd.)0.3 mg/kg and intravenously, during induction period, the other steps as usual. | Drug: etomidate<br>* 0.3mg/kg IV only once during induction of general anesthesia<br>* Other names: Fuerli;Drug: midazolam<br>* midazolam 0.1mg/kg IV only once before using of etomidate/propofol during induction of general anesthesia<br>* Other names: Liyuexi;|
| Active Comparator: midazolam & propofol<br>During induction period,use a bolus of midazolam injection 0.1mg/kg(Jiangsu Enhua Pharmaceutical Ltd.) and then a bolus of propofol injection 2mg/kg(Astrazeneca PLC.)intravenously, the other steps are as usual. | Drug: midazolam<br>* midazolam 0.1mg/kg IV only once before using of etomidate/propofol during induction of general anesthesia<br>* Other names: Liyuexi;Drug: propofol<br>* 2mg/kg IV only once during induction of general anesthesia<br>* Other names: Diprivan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in salivary cortisol at the operative day | At the time of 8am(baseline) and at the time of 8pm in the operative day , get salivary samples to calculate the change of salivary cortisol | baseline(8am), 8pm | 
| Change from baseline in salivary cortisol at the first day after surgery | At the time of 8am(baseline) and at the time of 8pm in the first day after surgery , get salivary samples to calculate the change of salivary cortisol | baseline(8am), 8pm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numbers of Acquired Infection Events | Acquired infection using extra antibiotics(not prophylactic antibiotics) after surgery. | up to 10 days after surgery | 
| Numbers of using inotropic drugs | Inotropic drugs include norepinephrine, adrenaline, phenylephrine and dopamine. | within 3 days | 
| Days of stay in intensive care unit (ICU) after surgery | Days of stay in ICU after surgery. | up to 10 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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salivary cortisol, circadian rhythm, children, etomidate