Dyphenhidramine Effect on Prevention of Sevoflurane Induced Post Anesthesia Agitation in Pediatric

The purpose of this study is to investigate the effect of diphenhydramine on the prevention of sevoflurane induced emergence delirium/ agitation in pediatrics. The Investigators hypothesis is that it reduce the incidence of sevoflurane induced emergence delirium/ agitation.

Study Overview

• Status: Completed
• Conditions: Specified Sedative; Hypnotic
• Intervention / Treatment: Drug: Diphenhydramine; Drug: Ketamine; Drug: Sevoflurane; Drug: Bupivacaine; Drug: normal saline

Detailed Description

This is an experimental clinical trial in double-blinded randomized controlled design on 50 children aged 10 months to 21 months who underwent general anesthesia with sevoflurane for labioplasty surgery. Fifteen minutes before inhalation anesthetics were discontinued, the subjects were randomly given a placebo or a single dose of diphenhydramine 0, 5 mg / kg intravenously. Subjects were extubated and observed in the recovered space conscious for any agitation or emergence delirium and feasability to return to the ward. Agitation or emergence delirium was assessed by the Pediatric Emergence Agitation and Delirium Score (PAEDS) whereas feasability to return to the ward scored with the Steward score. When PAEDS> 10 patients were assessed to be agitated or having emergence delirium and administeres rescue tranquilizer ketamine 0.1 mg / kg. Total rescue tranquilizers and clinically significant adverse effects of drugs also recorded.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 2 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

ASA I or 2

• no cardiovascular, respiratory or neurologic congenital anomalies
• no allergic reactions, or any contraindication to drugs used in this trial ever documented

Exclusion Criteria:

• congenital anomalies recognized/diagnosed during trial procedures
• hemmorhage > 15% EBV
• shock or other major anesthesia or surgical complications during trial procedures (hipoxia, atelectasis, unintended disconection of ETT or IV line)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: diphenhydramine; Subject sedated with sevoflurane, and given bilateral extraoral infraorbital block with 0,125% bupivacaine. Subject injected 0,5mg/kg diphenhydramine intravenously, 15 minutes prior to discontinuation of sevoflurane. If subject develop agitation, 0,1 mg/kg ketamine is administered	Drug: Diphenhydramine; Intravenous Injection; Drug: Ketamine; Ketamine 0,1 mg/kg intravenously used as rescue tranquilizer if the subject becomes agitated, repeated dose of 0,05 mg/kg every minute can be given if the agitation does not resolve, maximum ketamine dose for tranquilizer 0,25 mg/kg to prevent deep sedation; Drug: Sevoflurane; Sevoflurane as single sedation agent for general anesthesia in both arm. 8% Sevoflurane in 100% oxygen used as induction agent, and 2% sevoflurane in 50% oxygen used as maintenance agent; Drug: Bupivacaine; Bilateral extraoral infraorbital nerve block with 0,125% Bupivacaine as analgetic for operation and post operation.
Placebo Comparator: control; Subject sedated with sevoflurane, and given bilateral extraoral infraorbital block with 0,125% bupivacaine. Subject injected 0,5cc/kg normal saline intravenously, 15 minutes prior to discontinuation of sevoflurane. If subject develop agitation, 0,1 mg/kg ketamine is administered	Drug: Ketamine; Ketamine 0,1 mg/kg intravenously used as rescue tranquilizer if the subject becomes agitated, repeated dose of 0,05 mg/kg every minute can be given if the agitation does not resolve, maximum ketamine dose for tranquilizer 0,25 mg/kg to prevent deep sedation; Drug: Sevoflurane; Sevoflurane as single sedation agent for general anesthesia in both arm. 8% Sevoflurane in 100% oxygen used as induction agent, and 2% sevoflurane in 50% oxygen used as maintenance agent; Drug: Bupivacaine; Bilateral extraoral infraorbital nerve block with 0,125% Bupivacaine as analgetic for operation and post operation.; Drug: normal saline; Intravenous Injection; Other Names: NaCl 0,9%

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of sevoflurane induced post anesthesia agitation	10 minutes post extubation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amount of rescue Ketamine used	Administration of 0,1 mg/kg ketamine intravenously if the patient gets agitated	1 minute post extubation, at emergence, 15 minute post extubation
Significant adverse events	Any respiratory or cardiovascular events during observation in recovery room	1 minute post extubation, at emergence, 15 minute post extubation
Mean Pediatric Emergence Agitation and Delirium Score (PAEDS)		1 minute post extubation
Mean Pediatric Emergence Agitation and Delirium Score (PAEDS)		at emergence
Mean Pediatric Emergence Agitation and Delirium Score (PAEDS)		15 minute post extubation
Incidence of sevoflurane induced post anesthesia agitation		1 minute post extubation
Incidence of sevoflurane induced post anesthesia agitation		15 minute post extubation
Length of stay in recovery room		up to 15 minutes post extubation

Collaborators and Investigators

• Sponsor: Universitas Diponegoro
• Collaborators: Permata Sari Hospital for Plastic Surgery
• Investigators: Study Director: Johan Mr Arifin, dr, Universitas Diponegoro

Publications and helpful links

General Publications

• Koner O, Ture H, Mercan A, Menda F, Sozubir S. Effects of hydroxyzine-midazolam premedication on sevoflurane-induced paediatric emergence agitation: a prospective randomised clinical trial. Eur J Anaesthesiol. 2011 Sep;28(9):640-5. doi: 10.1097/EJA.0b013e328344db1a.
• Varughese AM, Rampersad SE, Whitney GM, Flick RP, Anton B, Heitmiller ES. Quality and safety in pediatric anesthesia. Anesth Analg. 2013 Dec;117(6):1408-18. doi: 10.1213/ANE.0b013e318294fb4a.
• Cohen IT, Finkel JC, Hannallah RS, Hummer KA, Patel KM. The effect of fentanyl on the emergence characteristics after desflurane or sevoflurane anesthesia in children. Anesth Analg. 2002 May;94(5):1178-81, table of contents. doi: 10.1097/00000539-200205000-00023.
• Abdallah C, Hannallah R. Premedication of the child undergoing surgery. Middle East J Anaesthesiol. 2011 Jun;21(2):165-74. No abstract available.
• Aouad MT, Nasr VG. Emergence agitation in children: an update. Curr Opin Anaesthesiol. 2005 Dec;18(6):614-9. doi: 10.1097/01.aco.0000188420.84763.35.
• Simons FE, Simons KJ. Clinical pharmacology of H1-antihistamines. Clin Allergy Immunol. 2002;17:141-78. No abstract available.

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: May 18, 2015
• First Submitted That Met QC Criteria: June 2, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Estimate): June 4, 2015
• Last Update Submitted That Met QC Criteria: June 2, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: emergence agitation; Withdrawal; pediatric anesthesia; Diphenhydramine; PAEDS
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Dyskinesias; Psychomotor Disorders; Psychomotor Agitation; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Platelet Aggregation Inhibitors; Antiemetics; Gastrointestinal Agents; Dermatologic Agents; Hypnotics and Sedatives; Anesthetics, Local; Anesthetics, Inhalation; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Ketamine; Diphenhydramine; Promethazine; Sevoflurane; Bupivacaine
• Other Study ID Numbers: UDiponegoro