Respiratory Quotient and Phosphate Changes During Early Critical Illness

Association Between Serum Phosphate and Respiratory Quotient During Early Critical Illness: A Prospective Observational Study Using Indirect Calorimetry

Critically ill patients often experience major changes in metabolism during the first days of intensive care. When nutrition is started or increased after a period of reduced intake, some patients may develop refeeding syndrome, a potentially serious condition associated with shifts in electrolytes such as phosphate, potassium, and magnesium.

This study will investigate whether changes in respiratory quotient (RQ), measured by indirect calorimetry, are associated with changes in serum phosphate during the first intensive care week. RQ reflects the balance between oxygen consumption and carbon dioxide production and provides information about which energy substrates are being used by the body. A rising RQ may indicate increasing carbohydrate metabolism and could potentially provide an early physiological marker of metabolic changes associated with refeeding.

Mechanically ventilated adult intensive care patients will undergo daily indirect calorimetry during the first five days of the study period, with an additional measurement on day 7 when feasible. Serum phosphate and other electrolytes, nutritional intake, insulin treatment, ventilator parameters, and relevant physiological variables will be recorded at corresponding time points.

The study will also evaluate how well established screening criteria for refeeding risk, including the NICE criteria, identify patients who subsequently develop metabolic changes consistent with refeeding. No study-specific changes to nutrition or other treatment will be made.

This accurately reflects the observational nature of the study: routine IC, laboratory and nutritional data are collected without changing treatment.

Indirect calorimetry (IC) provides measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2), allowing calculation of respiratory quotient (RQ) and resting energy expenditure (REE). RQ reflects the relative contribution of carbohydrate and fat oxidation and may therefore provide information about changes in substrate metabolism during the early phase of critical illness.

Refeeding syndrome is characterized by metabolic and electrolyte disturbances following initiation or escalation of nutritional therapy after a period of insufficient intake. A decrease in serum phosphate is one of its characteristic biochemical features. However, currently used clinical risk-screening tools have limited ability to identify which critically ill patients will subsequently develop metabolic changes associated with refeeding. The present study investigates whether longitudinal changes in RQ may provide additional physiological information regarding the development of refeeding-related metabolic changes. The protocol specifically examines whether rising RQ values, including values ≥0.90, occur in association with or shortly after a clinically relevant fall in serum phosphate, and whether low RQ values may precede subsequent phosphate decreases.

This is a prospective observational study conducted in mechanically ventilated adult patients admitted to the central and neurointensive care units at Sahlgrenska University Hospital. Participants will undergo daily indirect calorimetry during the first five study days, with an additional measurement on day 7 when feasible. Measurements are planned at a standardized morning time point after a stabilization period without changes in ventilator settings, nutrition, vasoactive medication, or sedation. Only measurements fulfilling predefined steady-state and technical-quality criteria will be included in the main analyses.

Serum phosphate, magnesium, potassium, and calcium will be recorded in temporal proximity to each indirect calorimetry measurement. Nutritional intake, including total energy and macronutrient delivery, as well as insulin treatment, PaCO2, temperature, ventilator parameters, and other relevant clinical variables will also be recorded. Risk of refeeding syndrome will be assessed using established NICE criteria at initiation of nutritional therapy.

The primary objective is to evaluate the within-participant association between serum phosphate and RQ over time. Longitudinal associations will be analyzed using mixed-effects regression models accounting for repeated measurements within participants. Time-lagged analyses will explore whether changes in RQ precede changes in serum phosphate or vice versa. Analyses will account for relevant potential confounders, including energy intake, carbohydrate intake, insulin treatment, PaCO2, and body temperature.

Secondary objectives include evaluation of the relationship between other electrolyte changes and metabolic measurements, characterization of longitudinal changes in RQ and REE during the early ICU course, and assessment of the ability of NICE refeeding-risk criteria to identify patients who subsequently demonstrate metabolic and biochemical changes compatible with refeeding.

The study is observational. No study-specific changes are made to nutritional treatment, ventilator settings, or other clinical management. Indirect calorimetry, laboratory testing, and nutritional monitoring are performed within established clinical care, with research-specific activities consisting of standardized collection and analysis of these data.

Inclusion Criteria:

• Age 18 years or older.
• Admitted to the central intensive care unit (CIVA) or neurointensive care unit (NIVA) at Sahlgrenska University Hospital.
• Receiving invasive mechanical ventilation.
• Expected intensive care stay longer than 72 hours.
• Enteral or parenteral nutritional therapy started or planned.
• Arterial catheter in place for clinically indicated blood sampling.
• Participation considered clinically safe by the responsible physician and research nurse.

Exclusion Criteria:

• Ongoing or planned continuous renal replacement therapy or intermittent - hemodialysis (CRRT/iHD).
• Extracorporeal membrane oxygenation (ECMO).
• Fraction of inspired oxygen (FiO2) >0.70.
• Severe renal failure or rapidly increasing creatinine without dialysis, where phosphate levels may not adequately reflect metabolic changes.
• Terminal illness or decision for end-of-life care.
• Previous participation in the study during the same ICU admission.