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Intravenous Chlorothiazide Versus Enteral Metolazone to Augment Loop Diuretic Therapy in the Intensive Care Unit
Michaud CJ, Mintus KC. Ann Pharmacother. 2017; 51: 286-92.
Study Question: Does IV chlorothiazide (CTZ) provide better clinical and safety outcomes compared to oral metolazone (MET) in critically ill patients already receiving loop diuretics?
Study Description: This was a retrospective, single-center study of adult patients admitted to either the cardiothoracic, medical or surgical ICU who received either CTZ or MET in addition to IV furosemide. The primary outcome was the change in urine output (UOP) 24 h pre- (furosemide-only) and post-study drug administration (intervention period).
Results: A total of 122 patients were included in the study, 58 patients in the CTZ group and 64 patients in the MET group. Baseline demographics slightly differed between the groups with more patients in the CTZ group having a left ventricular ejection fraction <30% (15% vs. 25%; p=0.03) as well as more patients having a left ventricular assist device (4% vs. 12%; p=0.02), compared to the MET group. No statistical difference was found in UOP during the furosemide-only period (p=0.09). CTZ significantly increased median UOP at 24 hours to a greater extent compared to MET (2405 vs. 1646 mL; p=0.01). CTZ provided a quicker onset of diuresis as compared to MET (p<0.01). No statistical differences were found in furosemide dosages, ICU LOS, hospital LOS, survival to discharge or progression to dialysis. Patients in the CTZ group required more potassium supplementation compared to the MET group (100 mEq vs. 57.1 mEq; p=0.01). The average cost of the intervention was significantly more in the CTZ group compared to MET ($96.50 vs. $7.90; p<0.01).
Conclusion(s): Administration of CTZ in critically ill patients receiving furosemide therapy provided faster and more robust diuresis, compared to MET.
Perspective: This study is the first to provide insight regarding which diuretic therapy is most beneficial to use in the critically ill patient population. Both MET and CTZ appear to provide added benefit to loop diuretic therapy without changing clinical or safety outcomes for patients. In this retrospective analysis, CTZ provided more diuresis with a faster onset; however CTZ does incur a heavier cost. It is appropriate for clinicians to consider this data when selecting between agents, while taking into consideration the limitations associated with this study’s retrospective nature.