Intravenous administration of conivaptan, an arginine vasopressin (AVP) receptor antagonist, has been demonstrated to be a safe and effective therapy for euvolemic and hypervolemic hyponatremia. In this case report, we report an extremely rapid correction of serum sodium with a typical dosing regimen of conivaptan. The patient was a 24 year woman who presented with nausea and vomiting, and was found on imaging to have two intracranial tumors, one of which was a large pituitary macroadenoma. Her serum sodium declined to 121mmol/L and intravenous conivaptan therapy was started. After approximately 25mg of conivaptan, her sodium increased 16mmol/L over 8.5hours. Fortunately, in this case, this correction was well tolerated, and the patient experienced no adverse effects of such a dramatic correction of serum sodium. Despite the good clinical result in this case, it should serve as a warning regarding the use of conivaptan, that although a gradual steady improvement in serum sodium can be expected in the majority of patients, more extreme corrections can be inadvertently achieved with even moderate doses. Thus, the exact clinical situation should be taken into consideration, especially in cases of subacute to chronic hyponatremia, where such an extreme correction could lead to neurologic devastation.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Neurocritical Care 02/2009; 11(1):14-9. DOI:10.1007/s12028-008-9179-3 · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hyponatremia [serum sodium concentration ([Na(+)]), <135 mEq/liter] is the most common fluid and electrolyte abnormality among hospitalized patients. It is frequently caused by the inappropriate release of arginine vasopressin.
The objective of this study was to evaluate the efficacy and safety of oral conivaptan, a vasopressin V(1A)/V(2) receptor antagonist, in patients with euvolemic or hypervolemic hyponatremia.
The study design was a 5-d placebo-controlled, randomized, double-blind study.
The study was performed at a hospital. Intervention: Oral conivaptan (40 or 80 mg/d) or placebo was given in two divided doses.
Seventy-four patients (average baseline serum [Na(+)], 115 to <130 mEq/liter) were studied.
The main outcome measure was the change from baseline in serum [Na(+)] area under the curve.
The least-squares mean change from baseline in the serum [Na(+)] area under the curve with conivaptan (40 and 80 mg/d) was 2.0-fold (P = 0.03) and 2.5-fold (P < 0.001) greater, respectively, than that with placebo. The median time to achieve a confirmed increase in serum [Na(+)] of 4 mEq/liter or more from baseline was 71.7 h for placebo, 27.5 h for 40 mg/d conivaptan (P = 0.044), and 12.1 h for 80 mg/d conivaptan (P = 0.002). The mean total times during which patients had a serum [Na(+)] level of 4 mEq/liter or more above baseline were 46.5, 69.8, and 88.8 h (P = 0.001), respectively. The least-squares mean change in serum [Na(+)] from baseline to end of treatment was 3.4 mEq/liter for placebo, 6.4 mEq/liter for 40 mg/d conivaptan, and 8.2 mEq/liter for 80 mg/d conivaptan (P = 0.002). A confirmed normal serum [Na(+)] (>/=135 mEq/liter) or increase of 6 mEq/liter or more was observed in 48% of patients given placebo, 71% given 40 mg/d conivaptan, and 82% given 80 mg/d conivaptan (P = 0.014). Headache, hypotension, nausea, constipation, and postural hypotension were the most common adverse events.
Oral conivaptan (40 and 80 mg/d) was well tolerated and efficacious in correcting serum [Na(+)] in hyponatremia.
[Show abstract][Hide abstract] ABSTRACT: This study assesses gender and age as independent risk factors for hypo- and hypernatremia and describes the prevalence of hypo- and hypernatremia in different population groups.
Details of all serum Na results with accompanying patient demographics for 2 years were downloaded from the laboratory database into Microsoft Access for multiple logistic regression analysis using SPSS. Female gender and age <30 years were the reference groups.
Data from 303577 samples on 120137 patients were available for analysis. Prevalence at initial presentation to a health care provider of Na<136, <116, >145, and >165 mmol/l were for acute hospital care patients: 28.2%, 0.49%, 1.43%, and 0.06%; ambulatory hospital care: 21%, 0.17%, 0.53%, and 0.01%; community care: 7.2%, 0.03%, 0.72%, and <0.01%. Age odds ratios rose with increasing age to 1.89 and 8.70 (Na<136 and <116 mmol/l) and 7.09 and 24.39 (Na>145 and >165 mmol/l, respectively) for age >81 years. Male gender was a mild risk factor for Na<136 mmol/l and was otherwise unimportant.
Hyponatremia is a common but generally mild condition while hypernatremia is uncommon. Increasing age is a strong independent risk factor for both hypo- and hypernatremia. Gender is not an important risk factor for disturbances of serum Na concentration.
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