Conivaptan for Hyponatremia in the Neurocritical Care Unit

Wright, Wendy L.; Asbury, William; Gilmore, Jane L; Samuels, Owen

doi:10.1007/s12028-008-9152-1

Cited by 64 publications

(40 citation statements)

References 13 publications

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“…Importantly, despite the properties of conivaptan as a V1a-receptor antagonist, it had no effect on systolic blood pressure or pulse rate. Conivaptan has been found to be effective in a heterogenous population of neurointensive care patients [95,96].…”

Section: Vasopressin Receptor Antagonistmentioning

confidence: 99%

Novel Treatment Targets for Cerebral Edema

2012

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Cerebral edema is a common finding in a variety of neurological conditions, including ischemic stroke, traumatic brain injury, ruptured cerebral aneurysm, and neoplasia. With the possible exception of neoplasia, most pathological processes leading to edema seem to share similar molecular mechanisms of edema formation. Challenges to brain-cell volume homeostasis can have dramatic consequences, given the fixed volume of the rigid skull and the effect of swelling on secondary neuronal injury. With even small changes in cellular and extracellular volume, cerebral edema can compromise regional or global cerebral blood flow and metabolism or result in compression of vital brain structures. Osmotherapy has been the mainstay of pharmacologic therapy and is typically administered as part of an escalating medical treatment algorithm that can include corticosteroids, diuretics, and pharmacological cerebral metabolic suppression. Novel treatment targets for cerebral edema include the Na(+)-K(+)-2Cl(−) co-transporter (NKCC1) and the SUR1-regulated NC Ca-ATP (SUR1/TRPM4) channel. These two ion channels have been demonstrated to be critical mediators of edema formation in brain-injured states. Their specific inhibitors, bumetanide and glibenclamide, respectively, are well-characterized Food and Drug Administration-approved drugs with excellent safety profiles. Directed inhibition of these ion transporters has the potential to reduce the development of cerebral edema and is currently being investigated in human clinical trials. Another class of treatment agents for cerebral edema is vasopressin receptor antagonists. Euvolemic hyponatremia is present in a myriad of neurological conditions resulting in cerebral edema. A specific antagonist of the vasopressin V1A-and V2-receptor, conivaptan, promotes water excretion while sparing electrolytes through a process known as aquaresis.Keywords Cerebral edema . Hyponatraemia . Osmotherapy . NKCC1 . SUR1/TRPM4 . Vaptan . Glyburide Overview of Perturbations in Brain Fluid HomeostasisCerebral edema in the neurointensive care setting can occur with a heterogenous group of neurological diseases, which typically fall under the categories of metabolic [1, 2], infectious [3], neoplastic [4], cerebrovascular [5][6][7], and traumatic [8,9] brain injury. Irrespective of the inciting process, cerebral edema results in the pathological accumulation of fluid in the brain's intracellular and extracellular spaces. This occurs secondary to alterations in the complex interplay between 4 distinct fluid compartments within the cranium; fluid is present within: 1) the blood in the cerebral blood vessels, 2) the cerebrospinal fluid in the ventricular system and subarachnoid space, 3) the interstitial fluid of the brain parenchyma, and 4) the intracellular fluid of the neurons and glia. These fluid compartments are not isolated, and specific movements of solutes and water from one compartment to another occur under normal conditions. When dysregulation of this normally tightly controlled fluid balance...

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Section: Vasopressin Receptor Antagonistmentioning

confidence: 99%

Novel Treatment Targets for Cerebral Edema

2012

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“…Murphy et al [11] describe the effect of 25 doses of conivaptan (20 or 40 mg bolus given C12 hr apart) in 19 patients with hyponatremia. In this study, 71% of patients responded to a single bolus of conivaptan with at least a 4 mEq/l increase in serum sodium (mean 5.8 ± 3.2 mEq/l) at 12 h; a sustained response >72 h was seen in 69% although the clinical effect as evaluated by urine specific gravity peaked at 2 h and returned to baseline by 12 h. Wright et al [12] report the effect of conivaptan (20 mg bolus followed by infusion of 20 or 40 mg/day) in 22 patients with hyponatremia. This treatment regimen with conivaptan induced at least a 6 mEq/l increase in serum sodium in 86% of patients.…”

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confidence: 52%

Non-Peptide Arginine-Vasopressin Antagonists (Vaptans) for the Treatment of Hyponatremia in Neurocritical Care: A New Alternative?

Fields

Bhardwaj

2009

Neurocrit Care

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“…It is hoped that the approval of tolvaptan in May 2009 will ease the treatment of euvolemic and hypervolemic hyponatremia since tolvaptan can be administered orally, eliminating the possibility of infusion site reactions that come with the current method of central line administration. 19 …”

Section: Discussionmentioning

confidence: 99%

Efficacy of 3% Saline vs. Conivaptan in Achieving Hyponatremia Treatment Goals

Domínguez

Pérez

2013

Methodist DeBakey Cardiovascular Journal

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Hyponatremia is the most common electrolyte abnormality encountered in clinical practice, but its optimal management is still evolving. While guidelines for infusion rates of hypertonic saline (HS) have been introduced, there is a risk of underestimating the response in serum sodium concentration after therapy. Guidelines also have evaluated the use of vasopressin receptor antagonists as alternatives or supplements to standard therapies. This single-center retrospective study from The Methodist Hospital (TMH) compared the effect of HS and conivaptan intervention in the management of 49 patients with hyponatremia from January 2009 through November 2010. Demographics, volume status, medical history, medication data, and serum sodium concentration correction over 48 hours were analyzed. No significant difference was noted with regard to age, ethnicity, gender, volume status, use of medications known to cause hyponatremia, or comorbidities. Baseline serum sodium concentration was not significantly different between HS (120.5 ± 3.8 mEq/L) and conivaptan (118.3 ± 6.7 mEq/L) groups. Regardless of whether the patient was euvolemic or hypervolemic, no significant difference was noted in serum sodium concentration at 4, 12, 24, or 48 hours after initiation of treatment or in frequency of over-correction between groups. This study compares the effect of HS to conivaptan intervention in the management of hyponatremia. No significant differences were identified in adherence to treatment guidelines. Further, based on this small retrospective study, neither agent poses a significant risk of over-correction at 4, 24, or 48 hours of therapy. for use in static conditions. Retrospective studies have found a risk of physicians underestimating the increase in [Na + ] after hypertonic saline therapy, particularly in the setting of extracellular volume depletion. 8,9 A common criticism of these formulae is that they fail to account for ongoing renal and extrarenal fluid and electrolyte losses. Whereas the formulae apply to static conditions, the dynamic nature of the patient's hospital course, including intravenous drips and gastrointestinal losses, affects the accuracy of [Na + ] replacement by standard calculated deficits. To this effect, more elaborate formulae have been developed 7 that better allow the clinician to follow [Na + ] levels at close time intervals to adjust medical management. EFFICACY OF 3% SALINE VS. CONIVAPTAN IN ACHIEVING HYPONATREMIA TREATMENT GOALSTreatment guidelines published in 2007 evaluated the situations in which vasopressin receptor antagonists should be considered as alternatives or supplements to standard therapies. 4 Conivaptan is one of these alternative therapies. 10,11 Conivaptan is a nonselective V 1A R/V 2 R vasopressin receptor antagonist available in IV form and approved by the FDA to treat euvolemic hyponatremia in 2005 and hypervolemic hyponatremia in 2007. There is a caveat to the use of conivaptan in hypervolemia: although vasopressin receptor antagonism could have potentially ...

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Conivaptan for Hyponatremia in the Neurocritical Care Unit

Cited by 64 publications

References 13 publications

Novel Treatment Targets for Cerebral Edema

Novel Treatment Targets for Cerebral Edema

Non-Peptide Arginine-Vasopressin Antagonists (Vaptans) for the Treatment of Hyponatremia in Neurocritical Care: A New Alternative?

Efficacy of 3% Saline vs. Conivaptan in Achieving Hyponatremia Treatment Goals

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