Effects and Mechanism of Pretreatment With Dexmedetomidine to Etomidate Induce Myoclonus

Effects and Mechanism of Pretreatment With Dexmedetomidine to Etomidate Induce Myoclonus During General Anesthesia Induction Period

By observing the difference of plasma homovanillic acid concentrations and brain electrical consciousness monitoring Narcotrend index, study the possible mechanism of influencing Etomidate induced myoclonus with Dexmedetomidine pretreatment during general anesthesia induction period.

Study Overview

• Status: Unknown
• Conditions: Myoclonus
• Intervention / Treatment: Drug: Low-dose Dexmedetomidine; Drug: Etomidate; Drug: midazolam，fentanyl，rocuronium; Drug: propofol，remifentanil，cis atracurium; Drug: High-dose dexmedetomidine; Drug: normal saline

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Sign the informed consent
• American Society of Anesthesiologists (ASA)classification:class I~II;undergoing elective surgery patients
• Aged between 18 and 55, 49-67 kg weight
• Body Mass Index（BMI）： 20-30 kg/m2
• Did not use any analgesic or sedatives drugs within 24 h pre-operation

Exclusion Criteria:

• Recently patients undergoing sedative drugs and antidepressant treatment
• Serious vision, hearing impairment or other reasons can not communicate
• Serious neurological disease, pregnancy, diseases of the cardiovascular system；
• BMI is Less than the standard 80% or higher than the standard 120%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low-dose Dexmedetomidine; -Pretreatment before anesthesia induction：Intravenous injection dexmedetomidine 0.5 µg/kg，completed within 15 minutes.	Drug: Low-dose Dexmedetomidine; Pretreatment：Intravenous injection dexmedetomidine 0.5 µg/kg ，completed within 15 minutes.; Other Names: Yisi; Drug: Etomidate; After 90 seconds of Pretreatment，intravenous infusion of etomidate fat emulsion 0.3mg/kg. -Does not offer any other drugs within 5 min after completion of etomidate.; Other Names: Fuerli; Drug: midazolam，fentanyl，rocuronium; Anesthesia induction：Intravenous injection midazolam 0.03 ~ 0.05 mg/kg, fentanyl 5 ~ 8 g/kg, rocuronium 0.6 mg/kg; Other Names: Liyuexi，Fentanyl Citrate Injection，Aikesong; Drug: propofol，remifentanil，cis atracurium; Anesthesia maintenance：Intravenous infusion of propofol 4 ~ 6 mg/kg/h, remifentanil 0.1 ~ 0.3 μg/kg/min, intermittent intravenous injection of cis atracurium 0.05 ~ 0.1mg/kg; Other Names: Propofol Injection，Ruifen，Cisatracurium Besylate Injection
Experimental: High-dose Dexmedetomidine; -Pretreatment before anesthesia induction：Intravenous injection dexmedetomidine 1 µg/kg，completed within 15 minutes.	Drug: Etomidate; After 90 seconds of Pretreatment，intravenous infusion of etomidate fat emulsion 0.3mg/kg. -Does not offer any other drugs within 5 min after completion of etomidate.; Other Names: Fuerli; Drug: midazolam，fentanyl，rocuronium; Anesthesia induction：Intravenous injection midazolam 0.03 ~ 0.05 mg/kg, fentanyl 5 ~ 8 g/kg, rocuronium 0.6 mg/kg; Other Names: Liyuexi，Fentanyl Citrate Injection，Aikesong; Drug: propofol，remifentanil，cis atracurium; Anesthesia maintenance：Intravenous infusion of propofol 4 ~ 6 mg/kg/h, remifentanil 0.1 ~ 0.3 μg/kg/min, intermittent intravenous injection of cis atracurium 0.05 ~ 0.1mg/kg; Other Names: Propofol Injection，Ruifen，Cisatracurium Besylate Injection; Drug: High-dose dexmedetomidine; Pretreatment：Intravenous injection dexmedetomidine 1 µg/kg ，completed within 15 minutes.; Other Names: Yisi
Placebo Comparator: normal saline Control group; -Pretreatment before anesthesia induction：Intravenous injection normal saline equal quantity，completed within 15 minutes.	Drug: Etomidate; After 90 seconds of Pretreatment，intravenous infusion of etomidate fat emulsion 0.3mg/kg. -Does not offer any other drugs within 5 min after completion of etomidate.; Other Names: Fuerli; Drug: midazolam，fentanyl，rocuronium; Anesthesia induction：Intravenous injection midazolam 0.03 ~ 0.05 mg/kg, fentanyl 5 ~ 8 g/kg, rocuronium 0.6 mg/kg; Other Names: Liyuexi，Fentanyl Citrate Injection，Aikesong; Drug: propofol，remifentanil，cis atracurium; Anesthesia maintenance：Intravenous infusion of propofol 4 ~ 6 mg/kg/h, remifentanil 0.1 ~ 0.3 μg/kg/min, intermittent intravenous injection of cis atracurium 0.05 ~ 0.1mg/kg; Other Names: Propofol Injection，Ruifen，Cisatracurium Besylate Injection; Drug: normal saline; Pretreatment：Intravenous injection normal saline equal quantity，completed within 15 minutes.; Other Names: Sodium Chloride Physiological Solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
myoclonus level	Level 0 ：no myoclonus happened;; Level 1 ：mild, tiny movement, one part of the body such as a finger or shoulder movement;; Level 2 ：moderate ,2 pieces of different muscle or slight movement of the muscle groups, such as face or legs;; Level 3 ：severely, 2 pieces or more muscle contracture intensity, such as fast outreach of limbs	when myoclonus occurs after emulsion injection is completed，assessed up to 5 minutes
Plasma homovanillic acid concentration（PHVA）		Measured when myoclonus occurs after emulsion injection is completed，assessed up to 5 minutes; if myoclonus does not appear,measured at 5 minutes after emulsion injection is completed.

Secondary Outcome Measures

Outcome Measure	Time Frame
Ramsay sedation score	1 min after entering the operating room; 1 min after dexmedetomidine injection is completed; 1 min after emulsion injection is completed;5 minutes after emulsion injection is completed；
Narcotrend index	1 min after entering the operating room; 1 min after dexmedetomidine injection is completed; 1 min after emulsion injection is completed;5 minutes after emulsion injection is completed；

Collaborators and Investigators

• Sponsor: Tang-Du Hospital
• Investigators: Principal Investigator: LI yumin, PHD, Air Force Military Medical University, China

Publications and helpful links

General Publications

• Schwarzkopf KR, Hueter L, Simon M, Fritz HG. Midazolam pretreatment reduces etomidate-induced myoclonic movements. Anaesth Intensive Care. 2003 Feb;31(1):18-20. doi: 10.1177/0310057X0303100103.
• Stockham RJ, Stanley TH, Pace NL, Gillmor S, Groen F, Hilkens P. Fentanyl pretreatment modifies anaesthetic induction with etomidate. Anaesth Intensive Care. 1988 May;16(2):171-6. doi: 10.1177/0310057X8801600207.
• Doenicke AW, Roizen MF, Kugler J, Kroll H, Foss J, Ostwald P. Reducing myoclonus after etomidate. Anesthesiology. 1999 Jan;90(1):113-9. doi: 10.1097/00000542-199901000-00017.
• Paris A, Philipp M, Tonner PH, Steinfath M, Lohse M, Scholz J, Hein L. Activation of alpha 2B-adrenoceptors mediates the cardiovascular effects of etomidate. Anesthesiology. 2003 Oct;99(4):889-95. doi: 10.1097/00000542-200310000-00022.
• Maze M, Virtanen R, Daunt D, Banks SJ, Stover EP, Feldman D. Effects of dexmedetomidine, a novel imidazole sedative-anesthetic agent, on adrenal steroidogenesis: in vivo and in vitro studies. Anesth Analg. 1991 Aug;73(2):204-8. doi: 10.1213/00000539-199108000-00015.
• Venn RM, Bryant A, Hall GM, Grounds RM. Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit. Br J Anaesth. 2001 May;86(5):650-6. doi: 10.1093/bja/86.5.650.
• Mizrak A, Koruk S, Bilgi M, Kocamer B, Erkutlu I, Ganidagli S, Oner U. Pretreatment with dexmedetomidine or thiopental decreases myoclonus after etomidate: a randomized, double-blind controlled trial. J Surg Res. 2010 Mar;159(1):e11-6. doi: 10.1016/j.jss.2009.07.031. Epub 2009 Aug 19.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): September 1, 2016

Study Registration Dates

• First Submitted: August 3, 2015
• First Submitted That Met QC Criteria: August 7, 2015
• First Posted (Estimate): August 10, 2015

Study Record Updates

• Last Update Posted (Estimate): August 10, 2015
• Last Update Submitted That Met QC Criteria: August 7, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Dexmedetomidine; Etomidate; myoclonus
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Dyskinesias; Myoclonus; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Analgesics; Sensory System Agents; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Neuromuscular Agents; Nicotinic Antagonists; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Remifentanil; Fentanyl; Midazolam; Propofol; Dexmedetomidine; Rocuronium; Etomidate; Cisatracurium; Atracurium
• Other Study ID Numbers: Tangdu-Eto-myo