Comparison of carbon dioxide control during pressure controlled versus pressure-regulated volume controlled ventilation in children (CoCO2): protocol for a pilot digital randomised controlled trial in a quaternary paediatric intensive care unit

Abstract

Introduction: Digital trials are a promising strategy to increase the evidence base for common interventions and may convey considerable efficiency benefits in trial conduct. Although paediatric intensive care units (PICUs) are rich in routine electronic data, highly pragmatic digital trials in this field remain scarce. There are unmet evidence needs for optimal mechanical ventilation modes in paediatric intensive care. We aim to test the feasibility of a digital PICU trial comparing two modes of invasive mechanical ventilation using carbon dioxide (CO₂) control as the outcome measure.

Methods and analysis: Single-centre, open-labelled, randomised controlled pilot trial with two parallel treatment arms comparing pressure control versus pressure-regulated volume control. Patients are eligible if aged <18 years, weighing >2 kg, have an arterial line and require >60 min of mechanical ventilation during PICU hospitalisation at the University Children's Hospital Zurich. Exclusion criteria include cardiac shunt lesions, pulmonary hypertension under treatment and intracranial hypertension. CO₂ is measured using three methods: end-tidal (continuous), transcutaneous (continuous) and blood gas analyses (intermittent). Baseline, intervention and outcome data are collected electronically from the patients' routine electronic health records. The primary feasibility outcome is adherence to the assigned ventilation mode, while the primary physiological outcome is the proportion of time spent within the target range of CO₂ (end-tidal, normocarbia defined as CO₂ ≥ 4.5 and ≤ 6 kPa). Both primary outcomes are captured digitally every minute from randomisation until censoring (at 48 hours after randomisation, extubation, discharge or death, whichever comes first). Analysis will occur on an intention-to-treat basis. We aim to enrol 60 patients in total. Recruitment started in January 2024 and continued for 9 months.

Ethics and dissemination: This study received ethical approval from the Cantonal Ethics Commission of Zurich (identification number: 2022-00829). Study results will be disseminated through publication in a peer-reviewed journal and other media like podcasts.

Trial registration number: NCT05843123.

Keywords: Electronic Health Records; PAEDIATRICS; Paediatric intensive & critical care; Randomised Controlled Trial.

Figure 1. Study design of the CoCO₂ randomised controlled trial. COCO₂, comparison of carbon dioxide control during pressure controlled versus pressure regulated volume controlled ventilation in children; ETCO₂, end-tidal carbon dioxide; FiO₂, Fraction of inhaled oxygen; MDSi, minimal dataset of the Swiss Society of Intensive Care; MV, minute vol; PC, pressure control; PEEP, positive end-expiratory pressure; PICU, Paediatric intensive care unit; PIM-2, Paediatric Index of Mortality version 2; Pinsp, peak inspiratory pressure; PRVC, pressure-regulated volume control; RR, respiratory rate; SpO₂, peripheral oxygen saturation; VT, tidal volume.

Figure 2. Graphical display and formulas used to calculate time-weighted averages for hypocarbia, hypercarbia and overall time spent outside the CO₂ target range. The formulas account for both the severity of the hypocarbia/hypercarbia and time spent under hypocarbia/above hypercarbia in the numerator, divided by the total time until censoring for each patient. CO₂, carbon dioxide.