Trace metal elimination during continuous sedation with propofol containing EDTA in critically ill patients

Introduction: Little is known about changes in serum and urinary zinc, cobalt, copper, iron, and calcium levels in the critically ill, or the effect of sedative agent preservatives such as disodium edetate (EDTA) on trace metal levels and elimination. Methods: ICU patients likely to need >24 hours of ventilator support in 23 ICUs were stratified by APACHE II score and randomized to receive propofol containing 0.005% EDTA (n=106) or sedative agents without EDTA (n=104). 24-hr urine samples were collected on days 2,3,7, and every 7 days thereafter for zinc, cobalt, copper, iron, and calcium excretion, EDTA levels, urine osmolality, albumin, and glucose. BUN, serum trace metals, creatinine and albumin were assessed at baseline and during each 24-hour urine collection. Results: 210 patients (144 men and 66 women age 18-88) completed the study. Baseline APACHE II scores and demographics were not significantly different. Mean sedation time was 149.1 (6.7-645) hrs. Vital signs, hematology, urinalysis and serum chemistry values, and incidence of adverse events were similar. Mean urinary zinc and iron excretion were higher on day 2 and 3, (p <0.05) and mean serum zinc levels on day 3 were lower for patients receiving propofol/EDTA than for patients receiving sedatives without EDTA. Urinary calcium excretion was lower in propofol/EDTA pts. on day 2 and 3. Mean serum iron concentrations were normal in both groups. No other clinically or statistically significant differences were observed. Renal function did not deteriorate during ICU sedation with either regimen. Conclusions: Propofol with EDTA was well tolerated by critically ill ICU patients. No adverse events indicative of trace metal deficiency were observed during a mean of 6.2 days. EDTA did not appear to compromise renal function.