Critical events in anaesthetised Kids undergoing tracheal intubation – a prospective, multi-centre observational study

Complications during airway management continue to be a major problem in paediatric anaesthesia. To improve patient safety, previously defined critical events associated with airway management during tracheal intubation in children will be recorded and analysed. The results of this study will be used to identify the extent of airway management related complications and design randomised controlled trials.

Objective(s): Assessment and analysis of the incidence of airway management related critical events during tracheal intubation in children.

Outcome(s): Primary endpoint: Primary study outcome is the incidence of anaesthesia cases with critical events associated with endotracheal intubation requiring intervention from the start of anaesthesia until the discharge of the patient from the post-anaesthesia care unit or end of anaesthesia (defined as handover to the paediatric or neonatal intensive care unit, the ward or discharge home straight from anaesthesia care) in children aged 0 - 16 years. Facultatively for those who do not have capacity the acquisition of data stops at the end of anaesthesia (defined as handover to the post-anaesthesia care unit).

Secondary endpoints: Secondary study outcome parameters are the incidences of the individual critical events associated with tracheal intubation as listed below and the number of critical events per case. Children with critical events will be followed up until resolution of the event or for a maximum of 30 days whichever comes earlier.

Study design: Prospective, international multi-centre observational trial. Participating centres will collect data over a consecutive period of three months.

**Measurements and procedures:**Patient characteristics and airway management techniques will be recorded using a dedicated CRF for all patients undergoing anaesthesia in the operating room will be collected. Should critical events associated with airway management occur, a second more detailed questionnaire will be completed by the anaesthetist in charge. Patients will be followed-up until the problem is resolved or for a maximum of 30 days whichever comes earlier.The observational data recording has no impact on patient care and/or clinical procedures. There is no direct benefit for the patients involved, but analysis might reveal problems with airway management and risk factors might be detected locally and internationally. Sites will be able to access local data for local quality improvement processes. This might result in general improvement of paediatric airway management through changes in airway management strategies, improved teaching or closing of technical gaps.

**Rationale:**The required number of centres will depend on the centres’ numbers of cases meeting the inclusion criteria. The sample size was determined based on (i) assumptions from previous studies regarding the incidence of critical airway events (estimated incidence of critical events related to tracheal intubation 1%) and (ii) the precision requirement that the relative error of the inferred incidence is within ±10% of the mean estimate. To be specific, the sample size was calculated with the aim that the inferred 95% confidence interval should lie between 0.9 – 1.1% with an estimated incidence of events of 1%. Recruitment of centres will be sequential, and centres will start their observational period of a consecutive three months at different time points, depending on availability of the relevant ethics committee approval and local resources of study personnel.

**Statistical Considerations:**Descriptive and inferential statistics for the incidence of critical airway events will be computed both for the entire cohort and for individual centres. A risk factor analysis for critical airway management related events will be performed by means of multivariable mixed-effect logistic regression analyses. Goodness-of-fit, calibration, discriminatory capacity and predictive skill of the regression models will be assessed by means of Nagelkerke pseudo r-squared, calibration belts, Area Under the Receiver Operating Characteristics (AUROC) and Brier Score, respectively. Given the uncertainty regarding the true underlying incidence of critical events related to tracheal intubation, an interim analysis is planned after 35’000 patients. The time point of the interim analysis is motivated by the fact that if the true incidence was 3% instead of the anticipated 1%, 35’000 patients would be the required sample size to achieve the required precision. No adjustment of the significance level at the interim and final analyses (i.e. methods like Pocock or O’Brien & Fleming) are employed given the inferential rather than hypothesis-testing nature of the study. The sample size will be updated based on the estimated inference during the interim analysis.