EMERGENCE AGITATION After Premedication IN PAEDIATRIC MAGNETIC RESONANCE IMAGING: A RETROSPECTIVE COHORT STUDY (premidazolam)

CLINICAL EVALUATION AND IMPACT ON EMERGENCE AGITATION OF AN ORAL SOLUTION OF MIDAZOLAM CONTAINING g-CICLODEXSTRIN IN PAEDIATRIC MAGNETIC RESONANCE IMAGING: A RETROSPECTIVE COHORT STUDY

The aim of this study was to assess the anxiolytic and sedative effect of OZALIN® / OZASED® (ADV6209) 0,25mg/Kg in children undergoing magnetic resonance imaging (MRI) under inhalational anesthesia. Our hypothesis is that compared to children who do not receive any premedication, palatability of OZALIN® / OZASED® by allowing an easier acceptance of the drug, improves the quality of anesthesia induction and postoperative behavioral outcome improving sedation and reducing the need for inhalation anesthetic which has been recognized as the main cause of post-procedural behavioral changes, including emergence agitation.

Study Overview

• Status: Completed
• Conditions: Brain Neoplasms; Autism Spectrum Disorder; Growth Retardation; Premedication; Brain Pathology

Detailed Description

Magnetic resonance imaging is considered the primary investigative tool for evaluating a wide range of paediatric medical conditions. Sedatives are often needed in this population to ensure immobilization during the acquisition of the images.

Midazolam has always been the most used anxiolytic-sedative drug in the pediatric population. Over time, the intravenous formulation of midazolam has been used also for oral, nasal or rectal administration but those alternative routes of administration represent an off-label use. Recently, in Europe was licensed ADV6209, a midazolam solution for oral use containing gamma-cyclodextrin (OZALIN® / OZASED®).

The aim of this study was to assess its anxiolytic and sedative effect at a dosage of 0,25mg/Kg in children undergoing magnetic resonance imaging (MRI) under inhalational anesthesia. Our hypothesis is that compared to children who do not receive any premedication, palatability of OZALIN® / OZASED® by allowing an easier acceptance of the drug, improves the quality of anesthesia induction and postoperative behavioral outcome improving sedation and reducing the need for inhalation anesthetic which has been recognized as the main cause of post-procedural behavioral changes, including emergence agitation.

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00135
    • Fondazione Policlinico Agostino Gemelli IRCCS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

the IRCCS Agostino Gemelli Foundation of Catholic University of Rome

Description

Inclusion Criteria:

- We included in the study 100 children (either gender), aged 1-10 years, American Society of Anaesthesiologists (ASA) physical status 1 and 3 who, between March and December 2022, received inhalation anesthesia for brain and spinal cord MRI for diagnostic investigations or postoperative and oncological follow-up

Exclusion Criteria:

• 1) a history of hypersensitivity to midazolam; 2) chronic therapy with benzodiazepines; 3) acute respiratory tract infections; 4) psychiatric and behavioural disorders; 5) ASA physical status >3.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Ozased group; 50 patients premedicated with OZALIN® / OZASED®
Control group; 50 patients who did not receive any premedication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluation of patients' reactive behavior to facemask positioning for inhalational anesthesia induction.	evaluation of patients' reactive behavior to facemask positioning for inhalational anesthesia induction evaluated on a four-point scale (Mask Acceptance Scale, MAS) indicating that child is cooperative and accept the mask readily (MAS=1), he is slight fearful and accepts the mask with mild resistance (MAS=2), with moderate struggle (MAS=3) or he resists strongly and must be restrained (MAS=4)	30 minutes within premedication administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the percentage of sevoflurane at which the child's eyes closed upon induction of general anesthesia	the percentage of sevoflurane at which the child's eyes closed upon induction of general anesthesia;	procedure (at induction of general anesthesia)
time to eye closure at induction of anesthesia;	time to eye closure at induction of anesthesia	procedure (at induction of general anesthesia)
patient degree of acceptance of the administered premedication	degree of acceptance of the administered premedication	30 minutes before induction of general anesthesia
evaluation of OZALIN® / OZASED® anxiolytic efficacy	OZALIN® / OZASED® anxiolytic efficacy was evaluated 30 minutes after premedication administration with the Ramsay sedation scale	30 minutes after premedication administration
child's behavior on separation from the parent	Child's behavior at the moment of separation from the parent just before induction of anesthesia was evaluated with a four-point Parental Separation Anxiety scale (PSAS)	baseline (before induction of general anesthesia)
occurrence of delirium at the emergence from anesthesia	The occurrence of emergence delirium at the end of the procedure was measured using the five items of the Pediatric Anesthesia Emergence Delirium scale (PAED)	at emergence of anesthesia procedure
evaluation of behavioural changes seven days after the procedure, between the two groups.	Maladaptive behavioural responses and developmental regression seven days after the procedure were evaluated by parents of children with the Post Hospitalization Behaviour Questionnaire for Ambulatory Surgery (PHBS-AS).	7 days after the magnetic resonance Imaging

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Rossella Garra, Fondazione Policlinico A. Gemelli IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): December 15, 2022
• Study Completion (Actual): December 15, 2022

Study Registration Dates

• First Submitted: July 7, 2023
• First Submitted That Met QC Criteria: July 13, 2023
• First Posted (Actual): July 14, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Postoperative Complications; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Central Nervous System Neoplasms; Nervous System Neoplasms; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Delirium; Brain Neoplasms; Emergence Delirium; Autism Spectrum Disorder
• Other Study ID Numbers: 0032517/22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Non completely planned yet
• IPD Sharing Time Frame: Non completely planned yet
• IPD Sharing Access Criteria: Not completely planned yet
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No