High vs low protein intake in chronic critical illness: A systematic review and meta-analysis

Patients with persistent organ dysfunction after the first week of intensive care unit (ICU) admission are considered to have chronic critical illness (CCI). Acquired muscle weakness is a common feature of CCI that is accompanied by loss of muscle mass and electromyographic features of myopathy. Optimizing protein intake may help prevent acquired muscle weakness and/or promote muscle recovery, however, the optimal level of protein intake in CCI is uncertain and there is a lack of consensus in published nutritional guidelines. This systematic review focuses on the impact of high versus low protein intake as part of a nutritional strategy for patients with CCI.

The terms "protein intake" and "critically ill" were systematically searched in PUBMED, CENTRAL (Cochrane Central Register of Controlled Trials), and WEB OF SCIENCE on 06/01/2023. We included studies that (1) enrolled critically ill adults (aged 18 years or over) who were in the ICU for more than 7 days and that compared (2) protein intake above and below 1.3 gr/kg administered by any route (enteral and/or parenteral), (3) had an intervention period that occurred primarily after the first 7 days of critical illness and (4) reported clinical outcomes including length of ICU and hospital stay, duration of invasive mechanical ventilation (IMV), mortality, ICU acquired infections, muscle mass and physical function. Studies pertaining to elective surgery, those with intervention periods shorter than 7 days or occurring primarily within the first 7 days of critical illness, those measuring only laboratory parameters as outcomes, and safety and feasibility studies were excluded.

Four studies were included (N = 1730) in the meta-analysis and systematic review. Higher (>1.3 g/kg/d) versus lower protein intake was associated with a decrease in early mortality (defined as ICU or 28-day mortality) hazard ratio (HR) 0.42 (95 % confidence interval (CI): 0.26-0.70, P < 0.001), but had no impact on late mortality (defined as the latest mortality timepoint in each study): HR 0.93 (95 % CI 0.76-1.15, P = 0.51). There was no significant difference between intervention and control groups with respect to duration of IMV, duration of ICU or hospital stay, muscle mass, or the incidence of ICU-acquired infections. One study reported improvements in physical function at 3 and 6 months in the intervention group.

After the first week of critical illness, increasing protein intake to >1.3 g/kg/d may improve early mortality but not late mortality or other clinical outcomes. The small number of relevant studies and the heterogeneity of outcomes assessed, weaken these conclusions. Further studies are warranted to discern whether higher protein intake is beneficial in chronic critical illness. PROSPERO registration number: CRD42023403554; PROSPERO registration name: "The effect of higher than 1,3 g/kg of protein versus lower intake in chronic critically ill patients".