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Management of Severe Hyponatremia: Infusion of Hypertonic Saline and Desmopressin Or Infusion of Vasopressin Inhibitors? Antonios H

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Management of Severe Hyponatremia: Infusion of Hypertonic Saline and Desmopressin Or Infusion of Vasopressin Inhibitors? Antonios H Marshall University Marshall Digital Scholar Pharmaceutical Science and Research Faculty Research Fall 11-2014 Management of Severe Hyponatremia: Infusion of Hypertonic Saline and Desmopressin or Infusion of Vasopressin Inhibitors? Antonios H. Tzamaloukas MD Joseph I. Shapiro MD Marshall University, [email protected] Dominic S. Raj MD Glen H. Murata MD Robert H. Glew PhD See next page for additional authors Follow this and additional works at: http://mds.marshall.edu/sp_psr Part of the Medical Pharmacology Commons, and the Medical Specialties Commons Recommended Citation Tzamaloukas AH, JI Shapiro, DS Raj, GH Murata, RH Glew and D Malhotra. Management of severe hyponatremia: infusion of hypertonic saline and desmopressin or infusion of vasopressin inhibitors? Am.J.Med.Sci. 2014,248(5):432-9. PMID:25247759. This Article is brought to you for free and open access by the Faculty Research at Marshall Digital Scholar. It has been accepted for inclusion in Pharmaceutical Science and Research by an authorized administrator of Marshall Digital Scholar. For more information, please contact [email protected]. Authors Antonios H. Tzamaloukas MD; Joseph I. Shapiro MD; Dominic S. Raj MD; Glen H. Murata MD; Robert H. Glew PhD; and Deepak Malhotra MD, PhD This article is available at Marshall Digital Scholar: http://mds.marshall.edu/sp_psr/55 REVIEW ARTICLE Management of Severe Hyponatremia: Infusion of Hypertonic Saline and Desmopressin or Infusion of Vasopressin Inhibitors? Antonios H. Tzamaloukas, MD, Joseph I. Shapiro, MD, Dominic S. Raj, MD, Glen H. Murata, MD, Robert H. Glew, PhD and Deepak Malhotra, MD, PhD 7 Abstract: Rapid correction of severe hyponatremia carries the risk of of osmotic demyelination syndrome is high. The expert panel osmotic demyelination. Two recently introduced methods of correction set also upper limits in the rate of correction. [Na]s should not rise of hyponatremia have diametrically opposite effects on aquaresis. by more than 8 mEq/L in any 24-hour period if the risk of Inhibitors of vasopressin V2 receptor (vaptans) lead to the production osmotic myelinolysis is high and by no more than 10 to 12 mEq/L in any 24-hour period or 18 mEq/L in any 48-hour period of dilute urine, whereas infusion of desmopressin causes urinary 7 fi if the risk of osmotic myelinolysis syndrome is not high. concentration. Identi cation of the category of hyponatremia that will fi fi Achieving the desired rate of correction of [Na]s is a dif - bene t from one or the other treatment is critical. In general, vaptans are fi effective in hyponatremias presenting with concentrated urine and, with cult task. In a recent report, the rise in [Na]s in the rst 24 hours of treatment exceeded 12 mEq/L in 11% of the subjects admitted the exception of hypovolemic hyponatremia, can be used as their 8 primary treatment. Desmopressin is effective in hyponatremias present- with severe hyponatremia. Saline infusion carries special risks of ing with dilute urine or developing urinary dilution after saline infusion. overcorrection of hyponatremia. The volume of infused saline is In this setting, desmopressin infusion helps prevent overcorrection of calculated by formulas that take into account the starting and the hyponatremia. Monitoring of the changes in serum sodium target [Na]s values, the concentration of sodium in the infusate and the volume of body water before the start of saline infu- concentration as a guide to treatment changes is imperative regardless 2,9 of the initial treatment of severe hyponatremia. sion. Lack of precision, or inaccuracy, of the clinical estimates of body water entered in the formulas used to calculate the vol- Key Indexing Terms: Hyponatremia; Vaptans; Desmopressin. [Am J ume of infused saline required for a specificrisein[Na] are – s Med Sci 2014;348(5):432 439.] important sources of error in the predictive formulas.2,10 The major source of error during treatment of hypona- tremia with saline infusion, however, is not accounted for in the yponatremia is considered severe when serum sodium con- predictive formulas. The source of this error is the volume and , 1 the concentrations of sodium and potassium of the urine during H centration ([Na]s)is 125 mmol/L and/or when hyper- tonic or isotonic saline is infused to correct severe neurological the treatment period.2 Two recently proposed strategies manifestations or symptomatic hypovolemia.2 In severe cases addressed specifically the effect of urine volume and composi- of hyponatremia, the rate of correction of [Na]s is critical for tion on [Na]s during treatment of severe hyponatremia. These prevention of either prolonged brain edema or osmotic demy- strategies, which include use of V2 vasopressin receptor inhib- elination.2 The current standard is a controlled rate of rise in itors (vaptans) and infusion of desmopressin along with saline, [Na]s. Although there is some debate about how rapid the initial have diametrically opposite effects on urinary free water excre- 3,4 increase in [Na]s should be in severe hyponatremia, there is tion. Vaptans increase water loss in the urine (aquaresis) with- strong evidence that the incidence of osmotic demyelination in- out changing urinary excretion of sodium or potassium; in creases sharply if the correction exceeds 20 mEq/L in the first 24 contrast, desmopressin promotes water reabsorption in the hours.5 Based on these observations, most experts recommend collecting ducts, thereby limiting urinary water loss. slower rates of correction.3–6 Recent guidelines from an expert It is therefore imperative to analyze the advantages, risks, panel recommend a minimum rate of correction of [Na]s by 4 to indications and contraindications of these 2 treatments for the 8 mEq/L per day, and a goal of 4 to 6 mEq/L per day if the risk various categories of hyponatremia. The recent guidelines address some of the uses of vaptans and desmopressin in hyponatremia.7 The purpose of this report was to provide a ratio- From the Renal Section, Medicine Service, Raymond G. Murphy VA Medical Center and Department of Medicine (AHT), University of New Mexico nale, based on the pathogenetic mechanism of each episode of School of Medicine, Albuquerque, New Mexico; Joan C. Edwards School of severe hyponatremia, for choosing vaptans or desmopressin Medicine (JIS), Marshall University, Huntington, West Virginia; Division of plus saline as the method of treatment of severe hyponatremia. Nephrology and Hypertension, Department of Medicine (DSR), The George We do not address alternative methods (eg, restriction of fluid Washington University, Washington, District of Columbia; Medicine Service, Raymond G. Murphy VA Medical Center and Department of Medicine (GHM), intake, administration of other than vaptan medications block- University of New Mexico School of Medicine, Albuquerque, New Mexico; ing the effect of vasopressin on the urinary concentrating mech- Department of Surgery (RHG), University of New Mexico School of Medicine, anism, urea infusion), all of which may have a role in the Albuquerque, New Mexico; and Division of Nephrology, Department of Med- management of severe hyponatremia in particular individuals. icine (DM), University of Toledo, Toledo, Ohio. Submitted February 26, 2014; accepted in revised form April 22, 2014. The authors have no financial or other conflicts of interest to disclose. This is an open access article distributed under the terms of the Creative RELATIONSHIP BETWEEN URINE COMPOSITION, Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it URINE FLOW RATE AND CORRECTION OF [Na]s is permissible to download and share the work provided it is properly cited. 2 As we have previously discussed, the changes in [Na]s The work cannot be changed in any way or used commercially. Correspondence: Deepak Malhotra, MD, PhD, University of Toledo— can be predicted based on various clinical parameters, including Health Science Campus, 3000 Arlington Avenue, Toledo, OH 43614-2598 initial body water volume, urine flow rate and electrolyte com- (E-mail: [email protected]). position, infusate volume and composition as well as dietary 432 The American Journal of the Medical Sciences Volume 348, Number 5, November 2014 Management of Hyponatremia ingestion and extrarenal salt and water losses. If we ignore figures, it seems very clear that infusion of substantial amounts extrarenal losses, the final serum sodium concentration after of hypertonic saline would be associated with very high rates of infusion of saline ([Na]Fin) is predicted by the equation: rise in [Na]s unless the urine remained very concentrated. Ergo, È É TBW 3 ½Na þ1:11 3 V 3 ½Na 2 V 3 ½Na þ½K ½ 5 Ini Ini Inf Inf Urine Urine Urine ; Na Fin TBWIni þ VInf 2 VUrine where TBWIni is total body water before the infusion, [Na]Ini is it would be predicted that the combination of vaptan therapy, the initial serum sodium concentration, 1.11 is an empiric cor- which would cause the elaboration of dilute urine, and hypertonic 11 rection term proposed by Edelman et al. VInf is the volume of saline would likely result in too-rapid rates of correction. Vaptans the infusate, [Na]Inf is the sodium concentration in the infusate, or desmopressin are indicated in certain categories of hyponatre- VUrine is the volume of urine and [Na]Urine and [K]Urine are the mia and are contraindicated or ineffective in other categories. concentrations of sodium and potassium in the urine, respectively. Using this formula and assuming starting points attribut- CATEGORIES OF HYPONATREMIA able to a 70-kg man with a serum sodium of 125 mEq/L, we One large group of hyponatremias is characterized by performed simulations shown in Figure 1. Reviewing these high serum vasopressin levels and urine osmolality levels that FIGURE 1. Simulations of the response of [Na]s depending on urine flow and electrolyte content as well as infusate composition and volume.
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