Effect of PEEP on Indirect Calorimetry in Critically Ill Patients

Indirect calorimetry (IC) is considered a reference method for assessment of energyexpenditure in critically ill patients. It measures oxygen consumption (VO2) and carbondioxide production (VCO2), from which respiratory quotient (RQ) and resting energyexpenditure (REE) are calculated. Reliable measurements are important when IC is used toguide nutritional therapy in mechanically ventilated intensive care patients.Measurement accuracy may potentially be influenced by ventilator settings and changes inrespiratory mechanics. Positive end‐expiratory pressure (PEEP) is frequently adjustedduring intensive care, but there is limited clinical evidence regarding whether changesin PEEP within commonly used ranges systematically affect contemporary indirectcalorimetry measurements. The approved research project therefore includes aphysiological substudy specifically examining the influence of PEEP on VO2, VCO2, RQ, andREE.This is a prospective, single‐center, repeated‐measures physiological study conducted inmechanically ventilated adult intensive care patients at Sahlgrenska University Hospital.Participants undergo indirect calorimetry during a standardized sequence of three PEEPlevels: 8, 12, and 16 cmH2O. Each participant therefore serves as their own control.At each PEEP level, the patient is allowed to reach a stable condition before indirectcalorimetry measurements are obtained. The ethics protocol specifies a stabilizationperiod before measurement and that other ventilator settings should remain unchangedduring the PEEP sequence. The final operational study protocol uses PEEP levels of 8, 12,and 16 cmH2O.Indirect calorimetry measurements will include VO2, VCO2, RQ, and REE. Measurements willbe performed under standardized conditions, with attention to measurement stability andventilator leakage. In the underlying research protocol, acceptable IC measurementperiods are defined using steady‐state criteria and controlled ventilator conditions.The primary objective is to determine whether VO2, VCO2, RQ, and REE changesystematically across PEEP levels of 8, 12, and 16 cmH2O. Repeated measurements will beanalyzed using mixed‐effects models accounting for clustering of observations withinparticipants.PEEP changes are performed within clinically accepted ranges under continuous intensivecare monitoring. The measurement sequence will be interrupted if clinically relevantdeterioration in hemodynamics, oxygenation, or other physiological parameters occurs. Theethics protocol specifically requires PEEP changes to remain within clinically acceptablelevels and to be discontinued if adverse physiological effects are observed.A relative difference of 10% in indirect calorimetry‐derived measurements between PEEPlevels was considered clinically meaningful. Assuming a within‐participant standarddeviation of approximately 12.5%, corresponding to a standardized paired effect size of0.8, approximately 15 evaluable participants are required to achieve 80% power at atwo‐sided alpha level of 0.05. To account for incomplete measurement sequences andtechnically inadequate indirect calorimetry measurements, 20 participants are planned forenrollment.