A Study on the Effects of Midazolam on Delirium After Sevoflurane Anesthesia in Pediatric Strabismus Surgery

Comparative Study on the Effects of Capacities of Midazolam on Delirium After Sevoflurane Anesthesia in Pediatric Strabismus Surgery : a Randomized Double- Blinded Trial

Sevoflurane with its rapid induction and emergence, hemodynamic stability, and nonirritating airway properties, has acquired widespread acceptance in children. However, sevoflurane has been reported to be associated with emergence agitation in children, with a reported incidence of up to 80%.

The purpose of this study is to verify that the prophylactic use of midazolam, which is a GABA A receptor inhibitor, given five minutes before the end of strabismus surgery reduces the incidence of emergence agitation after sevoflurane anesthesia in children. Simultaneously, this study aims to find out the proper dose of midazolam with minimum disturbance to patient's emergence time.

Study Overview

• Status: Completed
• Conditions: Child; Anesthesia Morbidity; Delirium on Emergence
• Intervention / Treatment: Drug: Midazolam 0.03mg/kg; Drug: Midazolam 0.05mg/kg; Drug: Placebo

Detailed Description

Sevoflurane is associated with a high incidence of emergence agitation in children. The etiology of emergence agitation is unclear. Some studies proposed that emergence agitation was related to a variable rate of neurologic recovery rate in different brain areas and immaturity of neurons. Inhalation anesthetics have been known to exert transient paradoxical excitatory effects in both animals and human patients, especially in children. The gamma(γ)-aminobutyric acid (GABA)A receptor is the target depressant effect site of most anesthetic drugs including sevoflurane. Midazolam acts on the benzodiazepine binding site of GABAA receptors and results in inhibitory effects on the central nervous system. The effect of midazolam premedication, as well as midazolam administration at the end of surgery, on suppressing emergence agitation has been studied. However, the effect of midazolam on emergence agitation is still controversial. This study aims to figure out the effect of midazolam at the end of surgery on emergence agitation during the recovery period, and find out the proper dose of midazolam with minimum disturbance to patient's emergence time.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 136-705
    • Department of Anaesthesiology and Pain Medicine Department; Korea University Anam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists physical status I and II patients
• Aged one to 13 years scheduled to undergo strabismus surgery under general anesthesia
• Willing to be assigned to any of the study intervention groups

Exclusion Criteria:

• Refusal by parents
• Neurological disease
• Developmental delay
• History of any previous surgery
• Airway disease
• American Society of Anesthesiologists physical status score of III or IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Midazolam 0.03mg/kg; This group will be injected intravenous midazolam 0.03mg/kg five minutes before the end of surgery.	Drug: Midazolam 0.03mg/kg; This group will be injected intravenous midazolam 0.03mg/kg five minutes before the end of surgery. If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.; Other Names: MIDAZOLAM BUKWANG INJ 5mg/5ml
Experimental: Midazolam 0.05mg/kg; This group will be injected intravenous midazolam 0.05mg/kg five minutes before the end of surgery.	Drug: Midazolam 0.05mg/kg; This group will be injected intravenous midazolam 0.05mg/kg five minutes before the end of surgery. If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.; Other Names: MIDAZOLAM BUKWANG INJ 5mg/5ml
Placebo Comparator: Placebo; This group will be injected intravenous normal saline five minutes before the end of surgery.	Drug: Placebo; This group will be injected intravenous normal saline five minutes before the end of surgery. If emergence agitation is severe, the patients will be treated by psychological support from the parents or nurse and intravenous fentanyl 1㎍/kg.; Other Names: NORMAL SALINE INJ(Sodium chloride 9g/1000mL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of emergence	The time of emergence is defined as time interval from the time of discontinuation of sevoflurane to the time of extubation.	within the first 1hour after end of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of emergency agitation	Agitation is assessed immediately after extubation, and continuously thereafter until participants are calm. Emergence agitation is evaluated using the four-point emergence scale and the pediatric anesthesia emergence delirium scale. The highest scores are recorded.	From just after extubation until the discharge of PACU, assessed up to 1 hour

Collaborators and Investigators

• Sponsor: Korea University Anam Hospital
• Investigators: Principal Investigator: Eun Jung Cho, Resident, Department of Anaesthesiology and Pain Medicine Department, Korea University Anam Hospital; Study Director: S.Z. Yoon, Professor, Department of Anaesthesiology and Pain Medicine Department, Korea University Anam Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): November 1, 2012

Study Registration Dates

• First Submitted: August 28, 2012
• First Submitted That Met QC Criteria: September 4, 2012
• First Posted (Estimate): September 7, 2012

Study Record Updates

• Last Update Posted (Estimate): January 4, 2013
• Last Update Submitted That Met QC Criteria: January 3, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: emergence agitation; midazolam; sevoflurane; strabismus
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Eye Diseases; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Cranial Nerve Diseases; Ocular Motility Disorders; Delirium; Strabismus; Emergence Delirium; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: ECho2012

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No