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Conivaptan Bolus Dosing for the Correction of Hyponatremia in the Neurointensive Care Unit

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Introduction 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.

Conclusion 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.

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  1. Lester MC, Nelson PB. Neurological aspects of vasopressin release and the syndrome of inappropriate secretion of antidiuretic hormone. Neurosurgery. 1981;8(6):735–40. doi:10.1097/00006123-198106000-00020.

    Article  PubMed  CAS  Google Scholar 

  2. Doczi T, Tarjanyi J, Huszka E, Kiss J. Syndrome of inappropriate secretion of antidiuretic hormone after head injury. Neurosurgery. 1982;10(6 Pt 1):685–8.

    PubMed  CAS  Google Scholar 

  3. Qureshi AI, Suri MF, Sung GY, et al. Prognostic significance of hypernatremia and hyponatremia among patients with aneurysmal subarachnoid hemorrhage. Neurosurgery. 2002;50(4):749–55. doi:10.1097/00006123-200204000-00012.

    Article  PubMed  Google Scholar 

  4. Rabinstein AA, Wijdicks EF. Hyponatremia in critically ill neurological patients. Neurologist. 2003;9(6):290–300. doi:10.1097/01.nrl.0000095258.07720.89.

    Article  PubMed  Google Scholar 

  5. Multz AS. Vasopressin dysregulation and hyponatremia in hospitalized patients. J Intensive Care Med. 2007;22(4):216–23. doi:10.1177/0885066607301360.

    Article  PubMed  Google Scholar 

  6. Pasantes-Morales H, Lezama RA, Ramos-Mandujano G, Tuz KL. Mechanisms of cell volume regulation in hypo-osmolality. Am J Med. 2006;119(Suppl 1(7)):S4–11. doi:10.1016/j.amjmed.2006.05.002.

    Article  PubMed  CAS  Google Scholar 

  7. Gullans SR, Verbalis JG. Control of brain volume during hyperosmolar and hypoosmolar conditions. Annu Rev Med. 1993;44:289–301. doi:10.1146/

    Article  PubMed  CAS  Google Scholar 

  8. Bhardwaj A. Neurological impact of vasopressin dysregulation and hyponatremia. Ann Neurol. 2006;59(2):229–36. doi:10.1002/ana.20788.

    Article  PubMed  CAS  Google Scholar 

  9. Fraser CL, Arieff AI. Epidemiology, pathophysiology, and management of hyponatremic encephalopathy. Am J Med. 1997;102(1):67–77. doi:10.1016/S0002-9343(96)00274-4.

    Article  PubMed  CAS  Google Scholar 

  10. Diringer MN, Zazulia AR. Hyponatremia in neurologic patients: consequences and approaches to treatment. Neurologist. 2006;12(3):117–26. doi:10.1097/01.nrl.0000215741.01699.77.

    Article  PubMed  Google Scholar 

  11. Singhi SC, Singhi PD, Srinivas B, et al. Fluid restriction does not improve the outcome of acute meningitis. Pediatr Infect Dis J. 1995;14(6):495–503. doi:10.1097/00006454-199506000-00006.

    Article  PubMed  CAS  Google Scholar 

  12. Wijdicks EF, Vermeulen M, Hijdra A, van Gijn J. Hyponatremia and cerebral infarction in patients with ruptured intracranial aneurysms: is fluid restriction harmful? Ann Neurol. 1985;17(2):137–40. doi:10.1002/ana.410170206.

    Article  PubMed  CAS  Google Scholar 

  13. Gross P, Reimann D, Henschkowski J, Damian M. Treatment of severe hyponatremia: conventional and novel aspects. J Am Soc Nephrol. 2001;12(Suppl 17):S10–4.

    PubMed  CAS  Google Scholar 

  14. Mohmand HK, Issa D, Ahmad Z, Cappuccio JD, Kouides RW, Sterns RH. Hypertonic saline for hyponatremia: risk of inadvertent overcorrection. Clin J Am Soc Nephrol. 2007;2(6):1110–7. doi:10.2215/CJN.00910207.

    Article  PubMed  Google Scholar 

  15. Woo MH, Kale-Pradhan PB. Fludrocortisone in the treatment of subarachnoid hemorrhage-induced hyponatremia. Ann Pharmacother. 1997;31(5):637–9.

    PubMed  CAS  Google Scholar 

  16. Wijdicks EF, Vermeulen M, van Brummelen P, van Gijn J. The effect of fludrocortisone acetate on plasma volume and natriuresis in patients with aneurysmal subarachnoid hemorrhage. Clin Neurol Neurosurg. 1988;90(3):209–14. doi:10.1016/0303-8467(88)90023-6.

    Article  PubMed  CAS  Google Scholar 

  17. Porzio P, Halberthal M, Bohn D, Halperin ML. Treatment of acute hyponatremia: ensuring the excretion of a predictable amount of electrolyte-free water. Crit Care Med. 2000;28(6):1905–10. doi:10.1097/00003246-200006000-00037.

    Article  PubMed  CAS  Google Scholar 

  18. Cawley MJ. Hyponatremia: current treatment strategies and the role of vasopressin antagonists. Ann Pharmacother. 2007;41(5):840–50. doi:10.1345/aph.1H502.

    Article  PubMed  CAS  Google Scholar 

  19. Hays RM. Vasopressin antagonists––progress and promise. N Engl J Med. 2006;355(20):2146–8. doi:10.1056/NEJMe068236.

    Article  PubMed  CAS  Google Scholar 

  20. Palm C, Pistrosch F, Herbrig K, Gross P. Vasopressin antagonists as aquaretic agents for the treatment of hyponatremia. Am J Med. 2006;119(Suppl 1(7)):S87–92. doi:10.1016/j.amjmed.2006.05.014.

    Article  PubMed  CAS  Google Scholar 

  21. Rabinstein AA. Vasopressin antagonism: potential impact on neurologic disease. Clin Neuropharmacol. 2006;29(2):87–93. doi:10.1097/00002826-200603000-00006.

    Article  PubMed  CAS  Google Scholar 

  22. Zeltser D, Rosansky S, van Rensburg H, Verbalis JG, Smith N. Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia. Am J Nephrol. 2007;27(5):447–57. doi:10.1159/000106456.

    Article  PubMed  CAS  Google Scholar 

  23. Ghali JK, Koren MJ, Taylor JR, et al. Efficacy and safety of oral conivaptan: a V1A/V2 vasopressin receptor antagonist, assessed in a randomized, placebo-controlled trial in patients with euvolemic or hypervolemic hyponatremia. J Clin Endocrinol Metab. 2006;91(6):2145–52. doi:10.1210/jc.2005-2287.

    Article  PubMed  CAS  Google Scholar 

  24. Vaprisol (conivaptan hydrochloride injection). Prescribing information. Deerfield Ill: Astellas Pharma US, Inc.; 2007.

    Google Scholar 

  25. Burnier M, Fricker AF, Hayoz D, Nussberger J, Brunner HR. Pharmacokinetic and pharmacodynamic effects of YM087, a combined V1/V2 vasopressin receptor antagonist in normal subjects. Eur J Clin Pharmacol. 1999;55(9):633–7. doi:10.1007/s002280050685.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Theresa Murphy.

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Murphy, T., Dhar, R. & Diringer, M. Conivaptan Bolus Dosing for the Correction of Hyponatremia in the Neurointensive Care Unit. Neurocrit Care 11, 14–19 (2009).

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