Dexamethasone and Postoperative Bleeding Following Tonsillectomy in Children (Blueberry)

Dexamethasone and Postoperative Bleeding Following Tonsillectomy in Children: Double-blind, Randomized, Placebo Control, Multi-centre, International, Pragmatic, Non-inferiority Trial

Tonsillectomy is one of the most frequently performed surgical interventions in children. However, it is associated with a high incidence of PostOperative Nausea and Vomiting (PONV), severe pain and haemorrhage. There is strong evidence on the efficacy of Dexamethasone in reducing the incidence of PONV and pain after tonsillectomy, which led to consider this drug as a first line treatment in routine anaesthesia practice in such surgical setting. However, in the last decade, there have been arguments about the potential role of Dexamethasone in increasing the risk of postoperative bleeding in children and studies addressing the haemorrhage risk following administration of Dexamethasone for tonsillectomy are inconclusive.Thus, this study is aimed at providing evidence for the safety profile of Dexamethasone with regard to the risk of post-tonsillectomy bleeding in children when administered as a single intraoperative dose.

This double-blind (investigator-surgeon-patient blinded), randomized, placebo control, multicentre, international, pragmatic, non-inferiority trial is designed to to provide evidence of the Dexamethasone safety profile with regard to the risk of post-tonsillectomy bleeding in children when administered as a single intraoperative dose of 0.15mg/kg. The study is also aimed at characterizing whether the co-administration of non steroidal anti-inflammatory drugs for analgesia potentiates the risk of postoperative haemorrhage. Sample size estimation is based on the definition of a minimal clinically important difference between the 2 groups of treatment (dexamethasone or normal saline) to be equal to 2% (non-inferiority margin). Thus, 3'794 children in total will be included with 1'897 children in each treatment group. The follow-up will be performed by the parents via an "Application" for Android and Apple that has been developed specifically for this study.

Double-blind (investigator-surgeon-patient blinded), randomized, placebo control, multi-centre, international, pragmatic, Non-inferiority trial.

Patients are allocated by block randomisation using sealed envelope system. An external person dedicated by Sponsor is in charge to randomize groups of treatment allocation through a website-generated list and to conceal the lists. Each centre receives the sealed opaque envelopes which contain treatment allocation. The envelope will be opened just before surgery. A member of the team not involved in the anaesthesia care will open an envelope and prepare the tested medication according to the result of randomization (Dexamethasone or NaCl). The repartition ratio between the 2 arms is 1:1 with a block size of 10.

Single intraoperative administration of 0.15 mg/kg of Dexamethasone intravenously with a maximum dose of 5 mg

7) Incidence of perioperative respiratory critical events: laryngospasm, bronchospasm, stridor, bronchial aspiration, hypoxia (Saturation in oxygen<90% for 2 minutes)

Assessment of pain scores at the hospital with the total score for the FLACC (Face, Legs, Activity, Cry, Consolability) scale for children less than 2 years of age and by the numeric pain rating scale above. Then at home, assessment by parents with the short version of the parents postoperative pain measurement.

2) Number of postoperative nausea and vomiting (PONV) and retching: during the stay at hospital with a maximum of 24 hours post-extubation

Any admission to high dependency unit or ICU, readmission for following reasons: Ear, Nose and Throat infection, dehydration, pulmonary infection, other pulmonary complications, seizure or bleeding not requiring reoperation

Inclusion Criteria: Children aged from 2 to 13 years admitted for tonsillectomy/ tonsillotomy with or without adenoidectomy Parents or legal responsible person willing and capable to follow data collection by the application (Android and iPhone) developed for this study Exclusion Criteria: Children under Aspirin or any other anticoagulants with or without Congenital Heart Disease Children with any bleeding disorders (ex. Haemophilia, Von Willebrand Disease)

De-identified individual participant data for all primary and secondary outcome measures will be made available

Data access requests from National coordinators or from local investigators will be examined by the steering committee and an agreement will be signed prior to Data access