Lactium Versus Midazolam Premedication on Postoperative Negative Behavioral Changes

Effect of Lactium Versus Midazolam Premedication on Postoperative Negative Behavioral Changes in Children Undergoing Adenotonsillectomy: A Randomized Double-blind Placebo-controlled Trial

This prospective randomized double-blind placebo-controlled study will be conducted to compare the effects of preoperative oral lactium and midazolam on the incidence of postoperative negative behavioral changes in young children undergoing adenotonsillectomy.

Study Overview

• Status: Not yet recruiting
• Conditions: Adenotonsillectomy; Behavior; Midazolam; Lactium
• Intervention / Treatment: Drug: Lactium; Drug: Midazolam; Other: Flavored oral solution

Detailed Description

Pre-anesthetic sedation may reduce postoperative negative behavioral changes. Midazolam, a benzodiazepine receptor agonist, has been used in attempts to improve child cooperation with anesthesia induction, though with reported variation in effectiveness for benefit at the different stages in the pre-, intra-, and postoperative periods. Lactium" is a synthetic derivative of alpha-s1 casein hydrolysate (ACH) containing the alpha-casozepine peptide, which is one of the main components of milk protein. It has been shown to interact with gamma-aminobutyric acid A receptors to provide anxiolytic and anti-stress effects. In this novel study, we hypothesize that the pre-emptive premedication by oral administration of lactium or midazolam can decrease the incidence of negative behavioral changes in children undergoing adenotonsillectomy.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Osama M Rehab, MD; Phone Number: 002 01095210806; Email: osamarehab@med.tanta.edu.eg

Study Locations

• Egypt
  • Gharbia Governorate
    • Tanta, Gharbia Governorate, Egypt, 31527
      • Tanta University Hospitals
      • Contact: Osama M Rehab, MD; Phone Number: 002 01095210806; Email: osamarehab@med.tanta.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children aged 3 to 12 years.
• American Society of Anesthesiologists (ASA) Physical Status I or II.
• scheduled for adenotonsillectomy under sevoflurane general anesthesia.

Exclusion Criteria:

• Parents declined to participate in the trial,
• Children with behavioral changes; neurological or psychiatric diseases
• Physical or developmental delay;
• Sedative or anticonvulsant medication;
• Pre-existing renal or cardiovascular disease.
• Allergy to midazolam or lactose.

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: Lactium group; Cases will receive preoperative lactium (5 mg/kg). Each lentra sachet (containing 150 mg Lactium) will be totally dissolved in 60 ml water and (2 ml/kg) will be given to cases, 2 hours before surgery with a maximum dose of 300 mg.	Drug: Lactium; cases will receive preoperative lactium, each lentra sachet (containing 150 mg Lactium) will be totally dissolved in 60 ml water and 5 mg/kg (2 ml/kg) will be given to cases, 2 hours before surgery with a maximum dose of 300 mg. Also, they will receive volume matched and flavored matched water 30 minutes before surgery. The cups and the syringes will be opaque.
Experimental: Midazolam group; Cases will receive preoperative 0.5 mg/kg oral midazolam (maximum 20 mg), 30 minutes before surgery.	Drug: Midazolam; cases will receive 2 ml/kg of water dissolved into it a sweet- vanilla flavored powder, 2 hours before surgery. Also, 0.5 mg/kg oral midazolam (maximum 20 mg) will be given 30 minutes before surgery.
Placebo Comparator: Control group; Cases will receive volume matched flavored solutions at each corresponding time point.	Other: Flavored oral solution; Cases will receive volume matched and flavored matched oral solution at each corresponding time point.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of negative behavioral changes at 24-h following surgery.	It will be assessed by a validated Arabic version of the Post Hospitalization Behavior Questionnaire (PHBQ). This is a 27-item questionnaire that was used to evaluate the child's behavior. Significant negative behavioral changes will be defined as ≥ 7 negative changes on the PHBQ items in comparison with the pre-anesthesia baseline values.	24 hours after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of negative behavioral changes at 3, 7, 14, 30 days following surgery.	It will be assessed by a validated Arabic version of the Post Hospitalization Behavior Questionnaire (PHBQ). This is a 27-item questionnaire that was used to evaluate the child's behavior. Significant negative behavioral changes will be defined as ≥ 7 negative changes on the PHBQ items in comparison with the pre-anesthesia baseline values.	Up to 1 month after surgery
Incidence of emergence delirium.	It will be evaluated using the Pediatric Anesthesia Emergence Delirium scale (PAED) scale. A score >12 together with a Delirium-specific score ≥ 9 will be considered a diagnostic endpoint for the development of delirium.	Up to 1 hour after surgery.
Parent separation anxiety.	It will be assessed at the time of taking the child to the operating theatre by the attending anesthesiologist using the Parent Separation Anxiety Scale (PSAS). (13) The PSAS ranges from one to four where one refers to easy separation; two equals whimpers; three denotes that the child cries and cannot be easily reassured but not clinging to parents; and 4 signifies crying and clinging to parents. A PSAS score of 1 or 2 was considered as 'acceptable' separation.	Perioperative.
Mask acceptance.	The ease of mask acceptance will be graded using the Mask Acceptance Score (MAS) at the time of induction of general anesthesia with sevoflurane. (14) The MAS scale is a 4-point Likert scale: 1 = excellent (unafraid, accepts mask readily); 2 = good (slight fear of mask, easily reassured); 3 = fair (moderate fear of mask, not calmed with reassurance); and 4 = poor (terrified, combative and crying). A MAS of 1 or 2 was considered 'satisfactory' mask acceptance	Perioperative.
Postoperative pain.	Postoperative pain will be assessed using the Face, Legs, Activity, Cry and Consolability (FLACC) scale at post-anesthesia care unit arrival and every 0.25 hour for 1 hour after surgery.	Up to 1 hour after surgery.
Extubation time.	At the end of surgery, the trachea will be extubated with the patient in the lateral position after confirmation that the gag reflex returned	End of surgery.
The total dose of rescue propofol.	Parental contact will be initiated as the first line management od delirium. If the PAED score remains at least 13 with a Delirium-specific score at least 9 despite parental contact, 1 mg/kg IV propofol will be administered. This dose will be repeated after 15 min if the child still agitated.	Up to 1 hour after surgery.
The total dose of rescue fentanyl.	A FLACC score of at least 4 will be treated with 0.5mcg/kg of IV fentanyl. This dose will be repeated after 15 min if the child still in pain. The total dose of rescue fentanyl will be recorded.	Up to 1 hour after surgery.
Anxiety scores.	anxiety scores before the administration of the study drugs and during parent separation and during anesthesia induction will be assessed by the modified Yale preoperative anxiety scale-short form (m-YPAS-SF).	Perioperative.
Side effects.	Postoperative nausea and vomiting, bradycardia, hypotension, respiratory events will be recorded.	Up to 1 hour after surgery.

Collaborators and Investigators

• Sponsor: Tanta University

Study record dates

Study Major Dates

• Study Start (Estimated): November 15, 2026
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): June 15, 2027

Study Registration Dates

• First Submitted: November 4, 2026
• First Submitted That Met QC Criteria: November 4, 2026
• First Posted (Actual): November 10, 2026

Study Record Updates

• Last Update Posted (Actual): November 10, 2026
• Last Update Submitted That Met QC Criteria: November 4, 2026
• Last Verified: November 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pharmaceutical Preparations; Chemical Actions and Uses; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Specialty Uses of Chemicals; Pharmaceutic Aids; Benzazepines; Benzodiazepines; Food Additives; Food Ingredients; Midazolam; Flavoring Agents
• Other Study ID Numbers: 36265PR276/10/26

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data will be available upon a reasonable request from the corresponding author.

IPD Sharing Time Frame

The data will be available upon a reasonable request from the corresponding author after the end of study for one year.

IPD Sharing Access Criteria

The data will be available upon a reasonable request from the corresponding author.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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