Analgosedation With Ketamine, Nalbuphine, or Dexmedetomidine for Suture Removal in Children After Cleft Surgery

NCT ID: NCT07340008

Last Updated: 2026-01-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2029-01-31

Brief Summary

This prospective, randomized study is designed to compare the efficacy and safety of three sedative-analgesic agents-intramuscular ketamine, intranasal nalbuphine, and intranasal dexmedetomidine-for procedural sedation in children undergoing suture removal following cleft palate, alveolar ridge, or lip surgery. The study will include 60 children aged 6 months to 3 years, randomly assigned to one of three intervention groups.

The primary objectives are to compare time to achieve adequate sedation (Modified Ramsay Sedation Scale 2-3), surgeon-rated ease of surgical procedure, and time to discharge readiness (Modified Aldrete Score ≥9). Secondary outcomes include baseline child behavior, response to drug administration, depth of sedation, response to separation from parents, and parental satisfaction, as well as monitoring of perioperative complications and vital signs.

All study medications are approved and commonly used in pediatric anesthesia. The trial will be conducted using non-invasive monitoring, with intravenous access established only in case of emergency interventions. Findings from this study are expected to provide evidence to optimize pediatric sedation protocols for minor surgical procedures.

Detailed Description

Title: Comparison of Intramuscular Ketamine and Intranasal Nalbuphine and Dexmedetomidine for Analgosedation in Children Undergoing Suture Removal After Surgery for Congenital Clefts of the Palate, Alveolar Ridge, and Lip

Introduction Orofacial clefts, including cleft lip with or without cleft palate and isolated cleft palate, are among the most common congenital craniofacial anomalies. Primary correction of a cleft lip may be performed between the 6th week and the 6th month of life, considering the child's growth, identification of associated anomalies, and avoidance of general anesthesia in the neonatal period. In cases of congenital cleft palate or alveolar ridge, correction is typically completed between 6 and 12 months of age.

Suture removal following these surgeries is a short procedure that requires optimal sedation and analgesia to enable efficient, rapid, and safe completion. The American College of Emergency Physicians (ACEP) defines procedural sedation as "a technique of administering sedatives or dissociative agents with or without analgesics to facilitate a procedure while maintaining cardiorespiratory function." The goal of sedation in pediatric patients is to avoid fear of medical professionals, injections, surgery, and the operating room environment. Effective sedation improves safety and comfort, reduces pain and anxiety, enhances the possibility of amnesia, and minimizes psychological trauma from separation from parents and exposure to an unfamiliar environment.

Ketamine is a dissociative anesthetic and analgesic, an NMDA receptor antagonist synthesized in 1962. It is favored for its analgesic and amnestic effects, preservation of airway reflexes, and various routes of administration (IV, IM, oral, rectal, nasal, epidural, intrathecal). However, ketamine may cause unpleasant hallucinations and hypersalivation. It is relatively contraindicated in patients with hypertension, increased intracranial pressure, respiratory infections, or underlying neuropsychiatric disorders.

Dexmedetomidine, approved by the FDA in 1999, is a selective α2-adrenoceptor agonist with strong sedative, analgesic, and anxiolytic properties, commonly used in pediatric intensive care units and diagnostic/therapeutic procedures. It may cause hypotension and bradycardia. Literature describes its pediatric use in intraoperative sedation, delirium management, postoperative analgesia, and shivering prevention.

Nalbuphine hydrochloride is a kappa-opioid receptor agonist and partial mu-antagonist. It exhibits a "ceiling effect," preventing respiratory depression. Nalbuphine is safe and effective for pediatric analgesia and sedation, and is administered via subcutaneous, IM, IV, or intranasal routes. Atomized intranasal delivery, using a Mucosal Atomizer Device (MAD), avoids painful IV access, offering a simple, safe, and effective method.

This study is designed to compare three sedatives-ketamine, dexmedetomidine, and nalbuphine-in children undergoing suture removal after cleft surgeries, focusing on perioperative sedation quality, procedural ease, application convenience, and safety profiles.

Protocol This prospective, randomized study will be conducted at the Department of Maxillofacial and Oral Surgery, University Medical Centre Ljubljana, in collaboration with anesthesiologists and surgeons.

A total of 60 children aged 6 months to 3 years requiring suture removal after cleft surgeries will be enrolled. Exclusion criteria include known allergy to the study drugs, ASA status greater than II, and lack of informed parental consent. After completion of the consent process, patients will be randomized into three groups.

Premedication with midazolam will be administered 30 minutes before the procedure. Group 1 will receive intramuscular ketamine (4 mg/kg) plus glycopyrrolate (4 mcg/kg) to reduce salivation. Group 2 will receive intranasal nalbuphine (0.5 mg/kg), and Group 3 intranasal dexmedetomidine (3 mcg/kg), delivered via MAD. Due to the short duration of the procedure and minimal risk, IV access will not be established unless complications arise.

If sedation is insufficient to complete the procedure, inhaled sevoflurane (starting at 2%, titrated by 0.5% increments) will be used as rescue medication.

Vital signs (heart rate, oxygen saturation, non-invasive blood pressure) will be monitored continuously. Blood pressure will be recorded three times: before drug administration, during the procedure, and prior to discharge. Additional monitoring will occur in case of adverse events. Heart rate and oxygen saturation will be recorded every 5 minutes before surgery, every 2 minutes during the procedure, and every 5 minutes post-procedure until discharge.

Sedation onset time, procedure duration, and recovery time will be evaluated. Complications (e.g., bronchospasm, aspiration, laryngospasm) will be documented, along with sedation depth (Modified Ramsay Scale), child's response to separation from parents, and surgeon-rated ease of procedure.

Statistical Methods It is expected that ketamine will demonstrate the fastest onset, dexmedetomidine the longest duration and calmest effect, and nalbuphine the most stable hemodynamics. Statistical analysis will include the Shapiro-Wilk test for normality. Normally distributed data will be expressed as mean ± SD, and non-normal data as median (IQR). Categorical variables will be presented as frequencies (%). Kruskal-Wallis test, Fisher's exact test, and Dunn's post-hoc test will be applied as appropriate. A p-value < 0.05 will be considered statistically significant. Analyses will be performed using SPSS 13.0 (SPSS Inc., Chicago, IL, USA).

Conditions

Orofacial Clefts; Cleft Lip and Palate; Alveolar Ridge Defect

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intramuscular Ketamine

Participants assigned to this arm will receive intramuscular ketamine at a dose of 4 mg/kg body weight for analgosedation during suture removal after surgery for congenital clefts. In addition, glycopyrrolate 4 mcg/kg will be administered intramuscularly to reduce salivation. This arm represents the control group, following the established clinical protocol.

Group Type: ACTIVE_COMPARATOR

ketamine

Intervention Type: DRUG

Intramuscular administration of Ketamine at 4 mg/kg body weight for analgosedation during suture removal in children after surgery for congenital clefts. Glycopyrrolate 4 mcg/kg will be co-administered to reduce salivation.

Intranasal Nalbuphine

Participants assigned to this arm will receive intranasal nalbuphine at a dose of 0.5 mg/kg body weight, administered using a mucosal atomizer device (MAD), for analgosedation during suture removal after cleft surgery. This intervention will be evaluated for its effectiveness, ease of administration, and safety compared with intramuscular ketamine.

Group Type: EXPERIMENTAL

Nalbuphine

Intervention Type: DRUG

Intranasal administration of Nalbuphine at 0.5 mg/kg body weight via mucosal atomizer device (MAD) for analgosedation during suture removal after cleft surgery in children.

Intranasal Dexmedetomidine

Participants assigned to this arm will receive intranasal dexmedetomidine at a dose of 3 mcg/kg body weight, administered using a mucosal atomizer device (MAD), for analgosedation during suture removal after cleft surgery. The intervention will be evaluated for sedation depth, response to separation from parents, and overall procedural ease compared with other sedative agents.

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Intranasal administration of Dexmedetomidine at 3 mcg/kg body weight via mucosal atomizer device (MAD) for analgosedation during suture removal after cleft surgery in children.

Interventions

ketamine

Intramuscular administration of Ketamine at 4 mg/kg body weight for analgosedation during suture removal in children after surgery for congenital clefts. Glycopyrrolate 4 mcg/kg will be co-administered to reduce salivation.

Intervention Type: DRUG

Nalbuphine

Intranasal administration of Nalbuphine at 0.5 mg/kg body weight via mucosal atomizer device (MAD) for analgosedation during suture removal after cleft surgery in children.

Intervention Type: DRUG

Dexmedetomidine

Intranasal administration of Dexmedetomidine at 3 mcg/kg body weight via mucosal atomizer device (MAD) for analgosedation during suture removal after cleft surgery in children.

Intervention Type: DRUG

Other Intervention Names

Ketamine Hydrochloride; Ketanest; Ketalar; Nalbuphine Hydrochloride; Nubain; Dexmedetomidine Hydrochloride; Precedex; Dexdor

Eligibility Criteria

Inclusion Criteria

• Age 6 months to 3 years
• Scheduled for suture removal after surgery for congenital cleft of the palate, alveolar ridge, or lip
• American Society of Anesthesiologists (ASA) physical status I or II
• Written informed consent obtained from parents or legal guardians
• Slovene-speaking family to ensure understanding and compliance
• No contraindications to the use of study medications

Exclusion Criteria

• Known allergy or hypersensitivity to ketamine, nalbuphine, or dexmedetomidine
• ASA physical status greater than II
• Significant neurological, psychiatric, or respiratory disorder
• Active or recent upper respiratory tract infection
• Refusal of parental or guardian consent
• Developmental disorder affecting communication or cooperation

• Minimum Eligible Age: 6 Months
• Maximum Eligible Age: 3 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Centre Ljubljana

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tadej P Dovšak, DDS, MD, PhD

Role: STUDY_CHAIR

University Medical Centre Ljubljana, Department of Maxillofacial and Oral Surgery

Locations

Department of Maxillofacial and Oral Surgery, University Medical Centre Ljubljana

Ljubljana, , Slovenia

Site Status: RECRUITING

Countries

Slovenia

Central Contacts

Liljana Markova, MD, PhD

Role: CONTACT

liljana.markova@kclj.si

00 386 40 802 662

Eleonora Ivanova, MD

Role: CONTACT

eleonora.ivanova@kclj.si

00 386 031 289 803

Facility Contacts

Liljana Markova, MD, PhD

Role: primary

liljana.markova@kclj.si

00 386 40 802 662

Eleonora Ivanova, MD

Role: backup

eleonora.ivanova@kclj.si

00386 31 289 803

Other Identifiers

TP 20240163

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

UKCLJ-KID-CLEFT-TP 20240163

Identifier Type: -

Identifier Source: org_study_id