The Effects of Spinal Anesthesia on ED50 and BIS50 of Etomidate for the Loss of Consciousness

Dose-Response Relationship, Drug Clinical Trial

— LOC  

Official title:

The Effects of Spinal Anesthesia on ED50 and BIS50 of Etomidate for the Loss of Consciousness

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03240055
• Other study ID #: mz2017
• Status: Completed
• Phase: N/A
• First received: July 21, 2017
• Last updated: September 2, 2017
• Start date: June 1, 2017
• Est. completion date: July 15, 2017

Study information

• Verified date: August 2017
• Source: General Hospital of Ningxia Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: July 15, 2017
• Est. primary completion date: July 15, 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Dose-Response Relationship, Drug
• Unconsciousness

Intervention

Drug:
• spinal anesthesia
The spinal puncture was performed with a 25 G Sprotte needle at the L3-4 or L2-3 interspinous space. Hyperbaric bupivacaine 0.5% (3 ml) was administered into the spinal space. Hyperbaric bupivacaine is obtained through the addition of glucose 10% (1ml) to bupivacaine 0.75% (2ml). Cerebrospinal fluid aspiration (0.1 ml) was done to confirm correct needle placement before and after spinal drug administration. Whereafter the patient was turned rapidly to the supine position, sensory anesthesia height was evaluated bilaterally using a pinprick test with the sharp tip of a safety pin every 1 min until 15 min after the initiation of the spinal anesthesia, bed tilting (upwards, horizontal, or downwards) was performed until bilateral sensory anesthesia level was confirmed to remain at the T4-T6 level

Other:
• etomidate
receive etomidate only

Locations

Country	Name	City	State
China	General Hospital of Ningxia Medical University	Yinchuan	Ningxia

Sponsors (1)

Lead Sponsor	Collaborator
General Hospital of Ningxia Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median effective dose (ED50)of etomidate at which 50% of patients lose consciousness	We want to determine Median effective dose (ED50) of etomidate at which 50% of patients lose consciousness in the SE and E group, respectively. It is a value,like 0.105mg/kg. Patients were considered to be loss of consciousness if there Observer's Assessment of Alertness/Sedation (OAA/S) scores were 2,1,or 0.	After etomidate administration to the lowest BIS value appears,usually about 4 minutes
Primary	BIS value (BIS50) of etomidate at which 50% of patients lose consciousness	We want to determine BIS value (BIS50) of etomidate at which 50% of patients lose consciousness in the SE and E group, respectively. It is a unitless value,like 60. Patients were considered to be loss of consciousness if there Observer's Assessment of Alertness/Sedation (OAA/S) scores were 2,1,or 0.	After etomidate administration to the lowest BIS value appears,usually about 4 minutes
Secondary	The change of Mean Arterial Pressure (MAP)		Baseline, l min (T1), 2min (T2), 3min (T3), 5min (T5) after administration of etomidate
Secondary	The change of heart rate (HR)		Baseline, l min (T1), 2min (T2), 3min (T3), 5min (T5) after administration of etomidate