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Continuous renal replacement therapy (CRRT) is commonly used in the care of critically ill patients although the optimal means of anticoagulation is not well defined. We report our regional CRRT protocol that was developed using the principles of quality improvement and compare the effect of regional citrate with systemic heparin anticoagulation on filter life span.Prospective observational cohort study in a Canadian adult regional critical care system. A standardized protocol for CRRT has been implemented at all adult intensive care units in the Calgary Health Region since August 1999. All patients with acute renal failure treated with CRRT during October 1, 2002, to September 30, 2003, were identified and followed up prospectively until hospital discharge or death.Eighty-seven patients with acute renal failure requiring CRRT were identified, 54 were initially treated with citrate, 29 with heparin, and 4 with saline flushes. Citrate and heparin were used in 212 (66%) and 97 (30%) of filters for 8776 and 2651 hours of CRRT, respectively. Overall median (interquartile range) filter life span with citrate was significantly greater than heparin (40 [14–72] vs 20 [5–44] hours, P < .001). The median time to spontaneous filter failure was significantly greater with citrate compared with heparin (>72 vs 33 hours, P < .001). Citrate anticoagulation resulted in greater completion of scheduled filter life span (59% vs 10%, P > .001). Citrate anticoagulation was well tolerated with no patient requiring elective discontinuation for hypernatremia, metabolic alkalosis, or hypocalcemia.Regional citrate anticoagulation was associated with prolonged filter survival and increased completion of scheduled filter life span compared with heparin. These data support small studies suggesting that citrate is a superior anticoagulant for CRRT and suggest the need for a future definitive randomized controlled trial.