The Effects of Spinal Anesthesia on ED50 and BIS50 of Etomidate for the Loss of Consciousness
Condition: Dose-Response Relationship, Drug
MeSH terms: Unconsciousness
Study type: Interventional

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
    

Intervention name(s): spinal anesthesia; etomidate
Intervention type(s): Drug; Other
Intervention description(s): 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; receive etomidate only
Intervention MeSH terms: Etomidate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Other
Keywords: spinal anesthesia; etomidate; median effective dose; BIS50