title: Conivaptan bolus dosing for the correction of hyponatremia in the neurointensive care unit.
abstract: BACKGROUND
  Hyponatremia frequently complicates acute brain injury and may precipitate neurological worsening by promoting cerebral edema. An increase in brain water may be better managed through water excretion than with fluid restriction or hypertonic fluids. Vasopressin-receptor antagonists such as conivaptan, which promote free water excretion, may be ideal agents to treat this common and potentially serious disorder.
  
  
  METHODS
  The efficacy of intermittent bolus doses of conivaptan to correct hyponatremia was examined in a consecutive series of patients treated in our neurointensive care unit. Patients were excluded if baseline sodium was over 135 mEq/l or if another conivaptan dose was given within 12 h. We assessed the proportion responding with a 4 or 6 mEq/l rise in sodium by 12 h, the change in sodium from baseline, and, in those not receiving another dose for at least 72 h, the long-term ability of a single dose to maintain sodium at least 4 mEq/l above baseline. We also recorded the effects of conivaptan on urine output and specific gravity, and noted any adverse events.
  
  
  RESULTS
  A total of 25 doses given to 19 patients were included (out of 44 total doses administered in the study period). Sodium rose by 5.8 +/- 3.2 mEq/l within 12 h, with 71% rising by at least 4 mEq/l and 52% manifesting at least a 6 mEq/l increase. In those receiving only a single dose, 69% maintained at least a 4 mEq/l rise up to 72 h. Conivaptan also consistently led to increased urine output and a significant drop in urine specific gravity (i.e., aquaresis). No cases of phlebitis were observed despite administration of conivaptan through peripheral IVs.
  
  
  CONCLUSIONS
  Intermittent dosing of conivaptan was effective in increasing free water excretion and correcting hyponatremia in neurologically ill patients. This supports its further evaluation for managing hyponatremia in this population.
authors.affiliation: Department of Pharmacy, Neurology/Neurosurgery Intensive Care Unit, Barnes-Jewish Hospital, Washington University School of Medicine, 216 S. Kingshighway Blvd, Saint Louis, MO 63110, USA. txm5120@bjc.org
authors.forename: Theresa
authors.initials: T
authors.lastname: Murphy
authors.forename: Rajat
authors.initials: R
authors.lastname: Dhar
authors.forename: Michael
authors.initials: M
authors.lastname: Diringer
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects; D003422:Critical Care / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007010:Hyponatremia / Q000097:blood / Q000188:drug therapy*; D007177:Inappropriate ADH Syndrome / Q000097:blood / Q000188:drug therapy*; D020551:Pulse Therapy, Drug; D012189:Retrospective Studies; D012964:Sodium / Q000097:blood; D013046:Specific Gravity / Q000187:drug effects; D014556:Urine
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; C106389:conivaptan; D012964:Sodium