Clinical trial NCT03240055: The Effects of Spinal Anesthesia on ED50 and BIS50 of Etomidate for the Loss of Consciousness
Official title: The Effects of Spinal Anesthesia on ED50 and BIS50 of Etomidate for the Loss of Consciousness
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dose-Response Relationship, Drug
Keywords: spinal anesthesia
etomidate
median effective dose
BIS50
Lead sponsor: General Hospital of Ningxia Medical University
Sponsor class: OTHER
First posted: 2017-08-04
Enrollment: 54
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to investigate the effect of spinal anesthesia on ED50 and BIS50 of etomidate for the loss of consciousness (LOC) by using up-and-down method.The hypothesis was that spinal anesthesia could significantly reduce the etomidate bolus dose for the LOC and could also achieve hemodynamic stability during anesthesia induction.

Detailed description: The combination of spinal with general anesthesia has been demonstrated to provide many clinically relevant advantages, however, this technique often experiences hypotension and bradycardia in the induction period of combined anesthesia. Etomidate is a carboxylated imidazole-derived hypnotic, and it is the most cardiovascularly stable intravenous induction drug, with the possible exception of ketamine. Meanwhile, the previous and our studies have been reported that spinal anesthesia has a direct sedative effect on animals and humans, and it markedly reduces the dose of hypnotic agents. To date, there is no dose-ranging study on the effect of spinal anesthesia on dosage of etomidate for the loss of consciousness (LOC). In the present study, investigators aim to investigate the effect of spinal anesthesia on the median effective dose (ED50) and the BIS value (BIS50) of etomidate at which 50% of patients lose consciousness compared to etomidate alone by using up-and-down method.

Patients were randomly allocated to one of two groups: only etomidate in group E (n=27) and spinal anesthesia combined with etomidate in group SE (n=21) using a randomization table. Patients in the SE group received spinal anesthesia first, and bilateral sensory anesthesia level was confirmed to remain at the T4-T6 level. After confirmation of the level of sensory anesthesia, the administration of etomidate was conducted. The etomidate (Nhwa Pharmaceutical, Jiangsu, China) starting dose of E group and SE group is 0.105 mg/kg and 0.089mg/kg, respectively. The dose of etomidate used for next patient was determined according to the response of the previously tested patient using the up-and-down method. If the patient lose consciousness, the dose of etomidate was reduced by one dose gradient for the next patient, and if didn't lose consciousness, the dose of etomidate was increased by one dose gradient (one dose gradient is r=1:0.85, that is, the ratio of high dose/low dose which are adjacent two doses). The testing of different dose levels of etomidate continued on consecutive randomised patients until a sample size of seven crossover points from "conscious" to "LOC" was reached

Eligibility criteria: Inclusion Criteria:

* ASA physical status I-II
* Body mass index (BMI) between 18.0 and 24.5 kg/m2
* Undergoing short elective laparotomy procedures, hysteroscopic and vaginal operation

Exclusion Criteria:

* Contraindication to spinal anesthesia
* Hearing loss
* History of cardiovascular disease, psychiatric and central nervous system diseases
* Hepatic or renal dysfunction
* Severe diabetes or hyperkalemia
* History of drug and alcohol abuse
* An allergy to amide local anesthetics or etomidate
* Adrenocortical hypofunction

Primary outcomes:
measure: Median effective dose (ED50)of etomidate at which 50% of patients lose consciousness
timeFrame: After etomidate administration to the lowest BIS value appears，usually about 4 minutes
measure: BIS value (BIS50) of etomidate at which 50% of patients lose consciousness
timeFrame: After etomidate administration to the lowest BIS value appears，usually about 4 minutes
Secondary outcomes:
measure: The change of Mean Arterial Pressure (MAP)
timeFrame: Baseline, l min (T1), 2min (T2), 3min (T3), 5min (T5) after administration of etomidate
measure: The change of heart rate (HR)
timeFrame: Baseline, l min (T1), 2min (T2), 3min (T3), 5min (T5) after administration of etomidate
Other outcomes:
Locations:
city: Yinchuan
country: China
facility: General Hospital of Ningxia Medical University
state: Ningxia
Study officials:
affiliation: General Hospital of Ningxia Medical University
name: Li Ningkang
role: PRINCIPAL_INVESTIGATOR
References: