Trace element homeostasis during continuous sedation with propofol containing EDTA versus other sedatives in critically ill patients

Objective:To evaluate changes in serum and urinary zinc, cobalt, copper, ir on, and calcium concentrations in critically ill patients receiving propofo l containing disodium edetate (disodium ethylenediaminetetraacetic acid [ED TA]) versus sedative agents without EDTA. Design: This was a randomised, op en-label, parallel-group study with randomisation stratified by baseline Ac ute Physiology and Chronic Health Evaluation (APACHE II) scores. Setting: Intensive care units (TCU) in 23 medical centres. Patients: Medical, surgical, or trauma ICU patients 17 years of age or olde r who required mechanical ventilator support and sedation. Interventions: A total of 106 patients received propofol containing 0.005 % EDTA (propofol EDTA), and 104 received other sedative agents without EDTA (non-EDTA). Only the first 108 patients were assessed for urinary trace met al excretion. Twenty-four-hour urine samples were collected on days 2, 3, a nd 7 and every 7 days thereafter for determination of zinc, cobalt, copper, iron, and calcium excretion; EDTA levels; urine osmolality; albumin levels ; and glucose levels. The first 143 patients were assessed for serum concen tration of zinc, cobalt, copper, iron, and calcium; creatinine; blood urea nitrogen; and albumin at baseline and once during each 24-hour urine collec tion. Measurements and Results: For the assessment of trace metals, patients rece iving propofol EDTA demonstrated increased mean urinary excretion of zinc, copper, and iron compared with the normal range. All patients receiving sed atives demonstrated increased urinary excretion of zinc and copper above no rmal reference values. Compared with the nonEDTA sedative group, the propof ol EDTA group demonstrated increased urinary excretion of zinc and iron. Me an serum concentrations of zinc and total calcium were decreased in both pa tient groups. Serum zinc concentrations increased from baseline to day 3 in the non-EDTA sedative group but not in the propofol EDTA group. Renal func tion, measured by blood urea nitrogen, serum creatinine, and creatinine cle arance, did not deteriorate during ICU sedation with either regimen. Conclusion: This study showed that critical illness is associated with incr eased urinary losses of zinc, copper, and iron. Propofol EDTA-treated patie nts had greater urinary losses of zinc and iron and lower serum zinc concen trations compared with the non-EDTA sedative group. No adverse events indic ative of trace metal deficiency were observed in either group. The clinical significance of trace metal losses during critical illness is unclear and requires further study.