Urinary pyridinium cross-link excretion is increased in critically ill surgical patients

Objectives: To determine: a) the rate of pyridinium cross-links of collagen excretion, breakdown products of bone, in critically ill surgical patients in the intensive care unit (ICU); and b) the relationship between cross-link excretion and nitrogen excretion and balance to ascertain whether collagen breakdown products contribute to protein losses during a hypercatabolic state. Design: Observational study starting on the first postoperative day to 20 days or until discharge. Setting: A surgical ICU in a University hospital. Patients: Nine mechanically ventilated, postoperative surgical patients (73 ± 3 [SD] yrs), receiving routine parenteral nutrition (18% protein) and 17 age-matched healthy subjects. Interventions: None. Measurements and Main Results: Resting energy expenditure was determined daily for ≤5 days after admission, and energy intake was set at 1.04 times the initial energy expenditure; thereafter, values of intake were reset weekly. Daily 24-hr urine samples were analyzed for cross-links, total and urea nitrogen, calcium, and creatinine for 20 days or until discharge. Two urine samples were also analyzed for cross-links in the healthy subjects. The excretion of cross-links from the surgical patients was markedly higher (p< .001) than in the healthy subjects, and calcium balance was significantly negative (p < .05). Patients who were discharged from the ICU within 5 days showed a lower rate of cross-link excretion (p < .02) and less day-to-day variability, compared with those patients who stayed longer, whether calculated over the course of the study or over the first 2 days in the ICU. There was no correlation between cross-links and energy expenditure, nitrogen excretion, or balance. Conclusions: The rate of cross-link excretion in critically ill patients: a) is markedly increased; b) is greater within the first two postoperative days in those patients who have an extended stay (>5 days) in the ICU; and c) is independent of the rate of nitrogen excretion. These findings suggest that critically ill postoperative patients experience an acute breakdown of collagen, which is likely due to resorption of bone or possibly comes from other collagen sources.