Background: Critically ill patients undergo rapid and clinically significant skeletal muscle loss during the first week of ICU admission, driven by a complex interplay of systemic inflammation, neuroendocrine dysregulation, and accelerated protein catabolism. While CRP is an established marker of the inflammatory response, its temporal relationship with early muscle wasting—specifically whether the initial inflammatory peak or its subsequent persistence most strongly determines muscle loss—remains poorly characterised. This study investigated the serial dynamics of inflammatory biomarkers and their correlation with skeletal muscle changes during the first seven ICU days.
Methods: This is a post hoc analysis of the NUTRITI prospective observational cohort, conducted at a single academic ICU in Udine, Italy (Ethics Committee approval: CEUR-2019-Os-17). Sixty-six adult critically ill patients with an anticipated ICU stay exceeding 72 h and requiring artificial nutritional support were included; patients on renal replacement therapy or with contraindications to bioelectrical impedance analysis (BIA) were excluded. Body composition—skeletal muscle mass (MM, kg) and phase angle (PA°)—was assessed by single-frequency BIA (50 kHz) on Day 1 and Day 7. The primary outcome was ΔMM%, the percentage change in muscle mass between admission and Day 7, calculated as ΔMM% = [(MMd − MMa)/MMa] × 100. Daily inflammatory biomarkers—CRP (mg/L), total WBC (×10
3/mm
3), and lymphocyte count (×10
3/mm
3)—were collected throughout. Spearman rank correlations between ΔMM% and serial biomarkers were computed for each day. Given the large number of tests (42 total), Bonferroni false discovery rate corrections were applied.
Results: The cohort had a median age of 68.5 years (IQR 61–77.8), was predominantly male (71.2%), with median APACHE II 21.5 and SOFA 7. Median muscle mass declined significantly from 34.3 kg (IQR 29.9–39.5) at Day 1 to 30.6 kg (IQR 26.5–34.9) at Day 7 (
p < 0.001), corresponding to a median MM% of −8.45% (IQR −14.2% to −1.52%). Phase angle also declined significantly (4.9° to 4.5°;
p < 0.01). CRP showed no significant correlation with ΔMM% at Days 1 or 2, but a negative correlation emerged at Day 3 (ρ = −0.297;
p = 0.020) and peaked at Day 4 (ρ = −0.355;
p = 0.006), attenuating thereafter. CRP at Days 5 and 6 correlated with phase angle changes (
p = 0.017 and
p = 0.022, respectively). WBC showed no significant correlations at any time point. Day-7 lymphocyte count was nominally correlated with ΔMM% (ρ = −0.314;
p = 0.040). Neither APACHE II nor SOFA at admission correlated with ΔMM%. No test survived correction for multiple comparisons.
Conclusions: The kinetics of CRP—rather than its initial intensity—seem to be associated with early skeletal muscle catabolism in critically ill patients, with a temporally specific signal emerging at Days 3–4 of ICU admission. Although these findings are exploratory and did not survive multiple testing correction, their biological plausibility—grounded in the known kinetics of ubiquitin-proteasome activation and NF-κB signalling—and their alignment with the emerging concept of inflammation-guided nutritional timing both support their value as a hypothesis-generating observation. Serial CRP monitoring may represent a pragmatic candidate biomarker to identify the optimal window for nutritional escalation, pending prospective validation in adequately powered trials.
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