Ketamine Gargle for Pain After Pediatric Tonsillectomy (KET-TONSIL)

Preemptive Topical Ketamine for Post-Tonsillectomy Analgesia: A Randomized, Double-Blind, Placebo-Controlled Trial in Children

Post-tonsillectomy pain in children is a common and clinically significant problem that may lead to poor oral intake, dehydration, and delayed recovery. This study evaluates whether a simple preoperative intervention-gargling with ketamine-can reduce postoperative pain and improve recovery after pediatric adenotonsillectomy.

In this randomized, double-blind, placebo-controlled trial, 420 children aged 4 to 12 years undergoing elective adenotonsillectomy were assigned to receive either a ketamine gargle (40 mg in saline) or a saline placebo prior to anesthesia induction. Pain intensity was measured using the Visual Analog Scale at multiple time points within the first 24 hours after surgery. Secondary outcomes included postoperative bleeding requiring reintervention, analgesic consumption, and adverse events.

The study aims to determine whether topical ketamine provides effective and safe analgesia as part of an opioid-sparing strategy in pediatric airway surgery.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain; Adenotonsillectomy; Tonsillectomy
• Intervention / Treatment: Drug: Ketamine Hydrochloride in saline; Other: Normal Saline (0.9% NaCl)

Detailed Description

Adenotonsillectomy is one of the most frequently performed surgical procedures in pediatric patients and is associated with significant postoperative pain. Effective analgesia remains challenging due to the need to balance efficacy with safety, particularly avoiding opioid-related respiratory complications. Topical ketamine, a non-competitive NMDA receptor antagonist, has been proposed as a peripheral analgesic strategy capable of reducing nociceptive signaling without significant systemic effects.

This study was designed as a prospective, randomized, double-blind, placebo-controlled trial conducted at a tertiary care center. A total of 420 pediatric patients (ASA I-II, aged 4-12 years) scheduled for elective adenotonsillectomy were enrolled. Participants were randomized in a 1:1 ratio to receive either a ketamine gargle (40 mg diluted in 30 mL saline) or a placebo saline gargle administered 5 minutes before induction of anesthesia.

All patients underwent standardized anesthetic and surgical protocols to minimize confounding variables. Pain intensity was assessed using the Visual Analog Scale at 0, 4, 8, 12, and 24 hours postoperatively. Secondary outcomes included incidence of postoperative hemorrhage requiring surgical reintervention, total rescue analgesic consumption, and adverse events such as nausea, vomiting, sedation, or psychomimetic effects.

The primary objective was to evaluate the analgesic efficacy of preemptive topical ketamine. Secondary analyses explored its potential impact on postoperative morbidity, particularly bleeding events. This study was conducted in accordance with ethical standards and CONSORT guidelines.

• Study Type: Interventional
• Enrollment (Actual): 420
• Phase: Phase 4

Contacts and Locations

Study Locations

• Venezuela
  • Miranda
    • Caracas, Miranda, Venezuela, 1040
      • VERAZA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Children aged 4-12 years
• ASA physical status I-II
• Scheduled for elective adenotonsillectomy
• Ability to gargle and spit the study solution

Exclusion Criteria:

• Known hypersensitivity to ketamine
• Coagulation disorders
• History of neuropsychiatric disease
• Active upper respiratory tract infection

Exclusion Criteria:

-

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KETAMINE GROUP; Preoperative gargle with 40 mg ketamine diluted in 30 mL saline, administered 5 minutes before induction of anesthesia.	Drug: Ketamine Hydrochloride in saline; Ketamine gargle at a dose of 40mg diluted in 30 mL of normal saline, administered 5 minutes before induction of anesthesia. Patients were instructed to gargle the solution for 30 seconds and then expectorate.; Other: Normal Saline (0.9% NaCl); Placebo gargle consisting of 30 mL of normal saline, administered 5 minutes before induction of anesthesia. Patients were instructed to gargle the solution for 30 seconds and then expectorate.
Experimental: PLACEBO GROUP; Preoperative gargle with 30 mL normal saline administered 5 minutes before induction.	Drug: Ketamine Hydrochloride in saline; Ketamine gargle at a dose of 40mg diluted in 30 mL of normal saline, administered 5 minutes before induction of anesthesia. Patients were instructed to gargle the solution for 30 seconds and then expectorate.; Other: Normal Saline (0.9% NaCl); Placebo gargle consisting of 30 mL of normal saline, administered 5 minutes before induction of anesthesia. Patients were instructed to gargle the solution for 30 seconds and then expectorate.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain intensity	Pain intensity measured using the Visual Analog Scale (VAS; 0-10) at predefined postoperative time points.	0, 4, 8, 12, and 24 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative hemorrhage requiring surgical reintervention	Incidence of postoperative bleeding requiring return to the operating room for hemostasis.	Within 24 hours postoperatively
Rescue analgesic consumption	Total requirement of additional analgesics (e.g., paracetamol or NSAIDs) within the first 24 hours after surgery.	24 hours postoperatively
Adverse events	Incidence of postoperative nausea and vomiting, sedation, or psychomimetic effects such as hallucinations or dysphoria.	24 hours postoperatively

Collaborators and Investigators

• Sponsor: Hospital Universitario de Caracas

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2024
• Primary Completion (Actual): January 7, 2025
• Study Completion (Actual): January 14, 2025

Study Registration Dates

• First Submitted: April 23, 2026
• First Submitted That Met QC Criteria: April 23, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: postoperative analgesia; pediatric anesthesia; NMDA receptor antagonist; ketamine gargle; opioid-sparing analgesia; airway surgery
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Pain, Postoperative; Organic Chemicals; Pharmaceutical Preparations; Hydrocarbons; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Sodium Compounds; Chlorides; Hydrochloric Acid; Ketamine; Saline Solution; Sodium Chloride
• Other Study ID Numbers: KET-AT-2024-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Individual participant data (IPD) sharing has not yet been determined. Data may be made available upon reasonable request to the corresponding author following publication, in accordance with institutional policies and applicable ethical regulations.

Drug and device information, study documents

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