title: Intravenous Chlorothiazide Versus Enteral Metolazone to Augment Loop Diuretic Therapy in the Intensive Care Unit.
abstract: BACKGROUND
  In cases of loop diuretic resistance in the intensive care unit (ICU), recommendations for a specific second-line thiazide agent are lacking.
  
  
  OBJECTIVE
  To compare the effects of intravenous chlorothiazide (CTZ) and enteral metolazone (MET) on urine output (UOP) when added to furosemide monotherapy therapy in critically ill adults.
  
  
  METHODS
  This was a retrospective cohort study conducted in the medical, surgical, and cardiothoracic ICUs of a quaternary medical center. The primary outcome was change in UOP induced by the study interventions compared with furosemide alone. Secondary outcomes included onset of diuresis, eventual need for hemodialysis, and incidence of adverse events.
  
  
  RESULTS
  A total of 122 patients (58 in CTZ, 64 in MET) were included. When added to furosemide monotherapy, CTZ induced a greater change in UOP at 24 hours compared with MET (2405 vs 1646 mL, respectively; P = 0.01). CTZ also caused a more rapid dieresis: 1463 mL total UOP in the first 6 hours compared with 796 mL in the MET group ( P < 0.01). There were no differences found regarding ICU length of stay, need for renal replacement therapy, or survival to discharge. The CTZ arm required more potassium supplementation to maintain normokalemia (median 100 vs 57 mEq in MET; P = 0.02) and carried a higher cost (mean $97 vs $8, P < 0.01).
  
  
  CONCLUSIONS
  Both CTZ and MET induced significant increases in UOP. CTZ induced a greater and more rapid change and was associated with higher cost and greater need for potassium replacement. Randomized controlled trials are needed to establish whether a preferable thiazide diuretic exists in this setting.
authors.affiliation: 1 Spectrum Health, Grand Rapids, MI, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Michaud
authors.affiliation: 2 Munson Medical Center, Traverse City, MI, USA.
authors.forename: Kendall C
authors.initials: KC
authors.lastname: Mintus
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D002740:Chlorothiazide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016638:Critical Illness; D004231:Diuresis / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008788:Metolazone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D049994:Sodium Potassium Chloride Symporter Inhibitors; D002740:Chlorothiazide; D005665:Furosemide; D008788:Metolazone
keywords: chlorothiazide; diuresis; intensive care unit; metolazone; sequential nephron blockade; thiazides