Response to a bolus of conivaptan in patients with acute hyponatremia after brain injury ☆ Theresa Human PharmD, BCPS a , Adaeze Onuoha MD b , Michael Diringer MD b , Rajat Dhar MD, FRCP(C) b, ⁎ a Department of Clinical Pharmacy, Neurology/Neurosurgery Intensive Care Unit, Barnes-Jewish Hospital, Saint Louis, MO, USA b Department of Neurology (Division of Neurocritical Care), Washington University School of Medicine, Saint Louis, MO 63110, USA Keywords: Hyponatremia; Vasopressin; Conivaptan; SIADH; Brain injury Abstract Purpose: The aim of the study was to analyze the response to the vasopressin-receptor antagonist conivaptan in a large cohort of brain-injured patients with acute hyponatremia. Materials and Methods: The natremic response (rise in serum sodium) to an initial bolus of conivaptan was retrospectively evaluated in 124 patients over a 3-year period in our neurosciences intensive care unit. Variables associated with this response were identified using linear regression. Results: Median pretreatment sodium was 132 mEq/L, and duration of hyponatremia before dose was 1 day. Median natremic response was +4 mEq/L (interquartile range, 2-7 mEq/L), measured a median of 9 hours (interquartile range, 6-12 hours) after conivaptan administration. This was associated with significant urine output (median, 2.6 L over 12 hours), with degree of aquaresis associated with natremic response (regression coefficient, B = 1.8 change in sodium per liter; 95% confidence interval, 1.3-2.4; P b .001). Seventy-four patients (60%) responded with a rise of at least 4 mEq/L. Response was predicted by higher baseline urine output (B = 0.018 per mL; 0.004-0.032; P = .01) and lack of oral fluid intake (B = 2.06; 0.44-3.68; P = .01) but not tonicity of intravenous fluids or creatinine clearance. Conclusions: Conivaptan given as a bolus can effectively treat acute hyponatremia in brain-injured patients. © 2012 Elsevier Inc. All rights reserved. 1. Introduction Acute hyponatremia is common among hospitalized patients and has been independently associated with worse outcomes [1,2]. It is an especially frequent complication in those with brain injuries, including head trauma and stroke [3,4], most often related to the syndrome of inappropriate release of antidiuretic hormone (SIADH). Secretion of antidiuretic hormone (ADH) leads to excess water reabsorp- tion and dilutional hyponatremia [5,6]. A fall in serum sodium ([Na + ]) and osmolality creates an osmotic gradient that promotes the shift of water into brain cells, which may exacerbate cerebral edema and precipitate neurologic deterioration [7-9]. The correction of hyponatremia in those with brain injuries is of paramount importance in ☆ Financial disclosures: Drs Human and Dhar have received speaking honoraria from Astellas Pharma but no funding to support this or any other studies. ⁎ Corresponding author. Department of Neurology (Campus Box 8111), St Louis, MO 63110, USA. Tel.: +1 314 362 2999; fax: +1 314 362 6033. E-mail address: dharr@neuro.wustl.edu (R. Dhar). 0883-9441/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcrc.2012.03.003 Journal of Critical Care (2012) 27, 745.e1–745.e5