Nephrology Dialysis Transplantation

NDT Advance Access published online on February 18, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfm932

This Article Abstract FREE Full Text (PDF) All Versions of this Article: 23/7/2223    most recent gfm932v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by Nguyen, M. K. Articles by Kurtz, I. Search for Related Content PubMed PubMed Citation Articles by Nguyen, M. K. Articles by Kurtz, I. Social Bookmarking          What's this?

© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

---

Correction of hypervolaemic hypernatraemia by inducing negative Na⁺ and K⁺ balance in excess of negative water balance: a new quantitative approach

Minhtri K. Nguyen and Ira Kurtz

Department of Medicine, UCLA Medical Center, Los Angeles, CA, USA

Correspondence and offprint requests to: Minhtri K. Nguyen, Division of Nephrology, David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Room 7-155 Factor Building, Los Angeles, CA 90095, USA. Tel: +1-310-206-6741; Fax: +1-310-825-6309; E-mail: mtnguyen{at}mednet.ucla.edu

	Abstract

Top Abstract Introduction Derivation of a new... Discussion Conclusion References

 
Hypervolaemic hypernatraemia is caused by an increase in total exchangeable Na⁺ and K⁺ in excess of an increment in total body H₂O (TBW). Unlike patients with hypervolaemic or euvolaemic hypernatraemia, treatment needs to be targeted at correcting not only the elevated plasma Na⁺ concentration, but also, there is an additional requirement to achieve negative H₂O balance to correct the increment in TBW. These seemingly conflicting therapeutic goals are typically approached by administering intravenous 5% dextrose (IV D5W) and furosemide. Correction of hypervolaemic hypernatraemia can be attained by ensuring that the negative Na⁺ and K⁺ balance exceeds the negative H₂O balance. Currently, there is no quantitative approach to predicting the volume of IV D5W (V_IVF) that needs to be administered that satisfies these requirements. Therefore, based on the principle of mass balance and the empirical relationship between exchangeable Na⁺, K⁺, TBW and the plasma Na⁺ concentration, we have derived a new equation that calculates the volume of IV D5W (V_IVF) needed to lower the plasma Na⁺ concentration ([Na⁺]_p1) to a targeted level ([Na⁺]_p2) by achieving the desired amount of negative H₂O balance (V_MB): V_IVF = {([Na⁺]_p1 + 23.8) (TBW₁) – ([Na⁺]_p2 + 23.8)(TBW₁ + V_MB) + 1.03 ([E]_input x V_input – [E]_output x V_output – [E]_urine (V_input – V_output – V_MB))}/1.03 x [E]_urine where [E] = [Na⁺ + K⁺] and input and output refer to non-infusate and non-renal input and output, respectively. This new formula is the first quantitative approach for correcting hypervolaemic hypernatraemia by achieving negative Na⁺ and K⁺ balance in excess of negative H₂O balance.

Keywords: dysnatraemia; hypernatraemia; hypervolaemia; sodium

	Introduction

Top Abstract Introduction Derivation of a new... Discussion Conclusion References

 
Hypernatraemia is a common electrolyte disorder in hospitalized patients [1]. It is a disorder characterized by either an absolute or relative free water deficit. In hypovolaemic or euvolaemic hypernatraemia, there is an absolute free water deficit characterized by the negative mass balance of H₂O (V_MB) (Table 1) [2]. Therefore, treatment of these clinical disorders is targeted at replacement of the free water deficit with hypotonic intravenous fluids. In contrast, hypervolaemic hypernatraemia is caused by an increase in total exchangeable Na⁺ and K⁺ in excess of the increment in total body water (TBW), resulting in a relative free water deficit [2]. Although these patients are hypervolaemic, they have a relative free water deficit because they develop a positive mass balance of Na⁺ and K⁺ (E_MB) in excess of the positive mass balance of H₂O (V_MB). Since these patients are hypervolaemic and hypernatraemic, treatment of these patients should be targeted at both the correction of the hypernatraemia and the attainment of a negative H₂O balance. Toward this goal, intravenous 5% dextrose (IV D5W) and furosemide can be utilized to correct the hypernatraemia as well as to achieve negative H₂O balance. In this article, we derived a new equation to help guide the correction of hypervolaemic hypernatraemia by inducing negative Na⁺ and K⁺ balance in excess of negative H₂O balance.

View this table: [in this window] [in a new window]   Table 1 Pathogenesis of hypernatraemia

 

	Derivation of a new formula for correction of hypervolaemic hypernatraemia by inducing negative Na+ and K+ balance in excess of negative water balance

Top Abstract Introduction Derivation of a new... Discussion Conclusion References

 
Based on the empirical relationship between the plasma water sodium concentration ([Na⁺]_pw) and the total exchangeable sodium (Na_e), total exchangeable potassium (K_e) and total body H₂O (TBW) originally demonstrated by Edelman et al. [3], we previously derived the Nguyen–Kurtz equation to predict the effect of simultaneous changes in the mass balance of Na⁺, K⁺ and H₂O and an increase in the plasma glucose concentration ([G]) on the plasma sodium concentration ([Na⁺]_p) in a given patient [4]:

(1)

where

y = 23.8 + (1.6/100)([G] –120)

[Na⁺]_p1 = Initial plasma [Na⁺]

[Na⁺]_p2 = Targeted plasma [Na⁺]

TBW₁ = Initial total body water

[E] = [Na⁺ + K⁺]

Input = non-infusate input

Output = non-renal output

Rearranging Equation 1,

(2)

Since IV D5W is the infusate used to correct hypervolaemic hypernatraemia, [E]_IVF = 0 and V_urine = V_IVF + V_input – V_output – V_MB, rearranging Equation 2,

(3)

Rearranging Equation 3,

(4)

Rearranging Equation 4,

(5)

In patients with euglycaemia, Equation 5 can be simplified as follows:

(5A)

	Discussion

Top Abstract Introduction Derivation of a new... Discussion Conclusion References

 
The mechanisms underlying the generation of hypernatraemia can be characterized according to the mass balance of Na⁺ and K⁺ (E_MB) in relation to the mass balance of H₂O (V_MB) (Table 1) [2]. In hypovolaemic hypernatraemia, the negative V_MB is the cause of the hypernatraemia, whereas the negative E_MB in this setting would lower the [Na⁺]_p, but its depressive effect is less than the incremental effect of the negative V_MB on the [Na⁺]_p. In these patients, a defect in the thirst mechanism or inadequate access to H₂O contributes to the negative V_MB. In euvolemic hypernatraemia, the negative V_MB is also the cause of the hypernatraemia, and E_MB is negligible in these patients. Although these patients actually have a negative V_MB, they appear clinically euvolaemic because only a small fraction of the total water loss originates from the intravascular space due the negligible E_MB. In contrast, in hypervolaemic hypernatraemia, it is the positive E_MB that is the cause of the hypernatraemia (rather than negative V_MB); the positive V_MB in these patients would tend to lower the [Na⁺]_p but is not of sufficient magnitude to prevent the [Na⁺]_p from increasing. In this setting, the compensatory V_MB is inadequate due to a defect in the thirst mechanism or inadequate access to H₂O.

Hypervolaemic hypernatraemia is therefore caused by an increase in total exchangeable Na⁺ and K⁺ in excess of the increment in TBW, resulting in a relative free water deficit [2]. Treatment of hypervolaemic hypernatraemia can be therapeutically challenging since the infusion of IV D5W alone will correct the hypernatraemia at the expense of worsening volume overload, whereas the administration of furosemide alone will treat the hypervolaemia at the expense of worsening hypernatraemia due to the urinary excretion of H₂O in excess of Na⁺ and K⁺. Consequently, treatment of hypervolaemic hypernatraemia needs to be targeted at correcting not only the elevated [Na⁺]_p, but also, there is an additional requirement to achieve a negative H₂O balance to correct the increment in TBW. These seemingly conflicting therapeutic goals are typically approached by administering intravenous D5W (IV D5W) and furosemide to correct the hypernatraemia as well as to achieve negative H₂O balance. Currently, there is no quantitative approach to predicting the volume of IV D5W (V_IVF) that needs to be administered that satisfies these requirements. Therefore, based on the principle of mass balance and the empirical relationship between exchangeable Na⁺, K⁺, TBW and the plasma Na⁺ concentration [3,4], we derived Equation 5 to help guide the correction of hypervolaemic hypernatraemia by inducing negative Na⁺ and K⁺ balance in excess of negative H₂O balance. Equation 5 calculates the volume of IV D5W (V_IVF) needed to lower the plasma Na⁺ concentration ([Na⁺]_p1) to a targeted level ([Na⁺]_p2) by achieving the desired amount of negative H₂O balance (V_MB). Since Equation 5 determines the volume of IV D5W required to lower the [Na⁺]_p as well as to attain the desired negative V_MB, it is implicit in the derivation of this equation that the negative mass balance of Na⁺ and K⁺ (E_MB) must be in excess of the negative mass balance of H₂O (V_MB). In other words, the negative E_MB must be greater than the negative V_MB in order for the [Na⁺]_p to be lowered in the setting of the negative V_MB (Figure 1).

View larger version (8K): [in this window] [in a new window] [Download PowerPoint slide]   Fig. 1 Hypervolaemic hypernatraemia is caused by an increase in EMB in excess of the increment in VMB, resulting in a relative free water deficit. Therefore, induction of a negative EMB in excess of the decrement in VMB is the most physiologic approach to treating hypervolaemic hypernatraemia.

 
Clinical utility of Equation 5
The utility of Equation 5A can be demonstrated in the following clinical case example: a 92-year-old Caucasian female with a history of congestive heart failure (CHF) secondary to diastolic dysfunction (ejection fraction 65%), hypertension and paroxysmal atrial fibrillation was admitted with recurrent symptoms of CHF. The patient reported four days of shortness of breath, orthopnea, paroxysmal nocturnal dyspnea and increasing lower extremity oedema. Physical examination is significant for jugular venous pressure 12 cm, bibasilar crackles and 2+ peripheral oedema. The patient was aggressively diuresed with intravenous furosemide. On Day 4 of her admission, she was noted to have a [Na⁺]_p = 150 mmol/L; however, she remained symptomatic with her CHF, and chest X-ray revealed cardiomegaly and persistent pulmonary oedema and interstitial hydrostatic pulmonary oedema with small bilateral pleural effusions.

The renal service was consulted to help guide the management of the hypernatraemia in the setting of persistent pulmonary oedema. The patient's hypernatraemia was thought to be secondary to inadequate free H₂O replacement in the setting of hypotonic urinary losses resulting from the aggressive diuresis. Since the patient was both hypernatraemic and hypervolaemic, intravenous D5W (IV D5W) was administered to correct the hypernatraemia and furosemide was continued to achieve the negative H₂O balance. Importantly, the goal of therapy was to administer the required volume of IV D5W (V_IVF) needed to lower the [Na⁺]_p from 150 mmol/L to 140 mmol/L while achieving the targeted 2 L of negative H₂O balance:

Parameters entered into Equation 5A:

[Na⁺]_p1 = 150 mmol/L

[Na⁺]_p2 = 140 mmol/L

TBW₁ = 30 L

V_MB = –2 L

[Na⁺ + K⁺]_urine = 80 mmol/L

According to Equation 5A, 5.6 L of IV D5W would be required to lower the [Na⁺]_p from 150 mmol/L to 140 mmol/L while achieving the desired 2 L of negative H₂O balance. Therefore, furosemide drip was titrated to attain a total urinary output of 7.6 L (V_MB = 5.6 L – 7.6 L = –2 L). Since the [Na⁺]_p decreased from 150 mmol/L to 140 mmol/L despite being in negative H₂O balance, the negative mass balance of Na⁺ and K⁺ (E_MB) must be in excess of the negative mass balance of H₂O (V_MB). The E_MB in this case was –608 mmol (E_MB = [E]_IVF x V_IVF – [E]_urine x V_urine = 0 – 80 x 7.6 = –608 mmol). Consequently, the net fluid loss resulting from the negative mass balance of Na⁺, K⁺ and H₂O was hypertonic (E_MB/V_MB = –608 mmol/–2 L = 304 mmol/L) to the patient's [Na⁺]_p, thereby resulting in a decrement in the [Na⁺]_p. This can also be verified by the known empirical relationship between the [Na⁺]_p and the exchangeable Na⁺ (Na_e), exchangeable K⁺ (K_e) and TBW [3,5]:

(6)

Therefore:

(7)

Na_e1 + K_e1 = (150 +23.8) x 30/1.03 = 5062 mmol

Na_e2 + K_e2 = Na_e1 + K_e1 + E_MB = 5062 – 608 = 4454 mmol

TBW₂ = TBW₁ + V_MB = 30 – 2 = 28 L.

Therefore,

Therefore, Equation 5A accurately determines the volume of IV D5W (V_IVF) needed to lower the [Na⁺]_p from 150 mmol/L to 140 mmol/L while achieving the desired 2 L of negative H₂O balance.

Etiologies of hypervolaemic hypernatraemia
Hypervolaemic hypernatraemia is typically iatrogenic in etiology. Hypervolaemic hypernatraemia is often induced by the administration of hypertonic sodium-containing solutions. Examples include massive ingestion of a highly concentrated saline emetic or gargle, accidental or non-accidental salt poisoning in infants and young children and the infusion of hypertonic sodium bicarbonate to treat metabolic acidosis [6–8]. More commonly, hypervolaemic hypernatraemia is induced by the inappropriate replacement of hyponatric fluid losses with an infusate containing a higher sodium concentration [9]. Indeed, Kahn reported that hypervolaemic hypernatraemia often results from the replacement of hyponatric fluid losses (hyponatric fluid losses via sweat, gastric aspiration, diarrhea and diuretics) with isotonic saline in subjects with salt-retaining states [9]. In all these clinical scenarios, treatment of the hypervolaemic hypernatraemia necessitates the induction of a negative Na⁺ and K⁺ balance in excess of the negative H₂O balance in order to ameliorate both the hypernatraemia and the hypervolaemic state.

Hyperglycaemic states
In the setting of hyperglycaemia, Equation 5 must be utilized instead of Equation 5A to guide the treatment of hypervolaemic hypernatraemia. It is well known that there is an expected decrease of 1.6 mmol/L in the plasma [Na⁺] for each 100 mg/dL increment in the plasma glucose concentration resulting from the dilutional effect of hyperglycaemia induced by the translocation of water [10]. Therefore, in hyperglycaemic states, the severity of the hypernatraemia is often unrecognized due to the dilutional effect of hyperglycaemia on the plasma [Na⁺]. In this setting, the severity of the hypernatraemia is often unmasked with correction of the hyperglycaemia.

Importantly, we have previously demonstrated that the y-intercept in Equation 6 is not constant and will vary predictably with the plasma glucose concentration [2,4,5]. Moreover, we have previously shown [2,4,5] that the plasma [Na⁺] varies with the plasma glucose concentration according to Equation 8:

(8)

Equation 5, therefore takes into consideration the dilutional effect of hyperglycaemia on the plasma [Na⁺] by accounting for the fact that the y-intercept, y = 23.8 + (1.6/100)([G] –120), is not constant and will vary predictably with the plasma glucose concentration [2,4,5].

In hyperglycaemia, the glucosuria-induced osmotic diuresis will also lead to the urinary excretion of H₂O in excess of Na⁺ + K⁺, resulting in increased urinary electrolyte-free water excretion [11]. The increased urinary electrolyte-free water excretion induced by glucosuria will in turn lead to exacerbation of the underlying hypernatraemia. In diabetic patients, oral water replacement may therefore be preferable to IV D5W to avoid hyperglycaemia. However, in patients who are on bowel rest (NPO), IV D5W can be used with close monitoring of the plasma glucose concentration and tight control of the diabetes.

Limitations of Equation 5
There are limitations that one has to take into account when using Equation 5. First, one must take into consideration the fact that there may be dynamic changes in the mass balance of Na⁺, K⁺ and H₂O during treatment. Therefore, the patient's input and output of Na⁺, K⁺, H₂O and the plasma [Na⁺] must be monitored frequently to guide further adjustments in the fluid prescription. The frequency with which this needs to be done will be determined by the clinical course and constancy of input and output sources in a given patient. Finally, the accuracy of Equation 5 is dependent on an accurate estimate of the TBW. In this regard, the regression equations reported by Watson et al. can be used to provide an accurate estimate of TBW [12].

	Conclusion

Top Abstract Introduction Derivation of a new... Discussion Conclusion References

 
In summary, hypervolaemic hypernatraemia is caused by an increase in total exchangeable Na⁺ and K⁺ in excess of the increment in TBW, resulting in a relative free water deficit. Since these patients are hypernatraemic and hypervolaemic, treatment needs to be targeted at correcting not only the hypernatraemia but also to achieve a negative H₂O balance to correct the increment in TBW. In this setting, both intravenous D5W (IV D5W) and furosemide are administered to correct the hypernatraemia and to achieve a negative H₂O balance. Therefore, correction of hypervolaemic hypernatraemia can be attained by ensuring that the negative Na⁺ and K⁺ balance exceeds the negative H₂O balance. In this article, we derived a new equation to predict the volume of IV D5W (V_IVF) that needs to be administered that satisfies these requirements. This new equation is the first quantitative approach for correcting hypervolaemic hypernatraemia by achieving negative Na⁺ and K⁺ balance in excess of negative H₂O balance. This new equation should be especially helpful in providing the clinician with a quantitative approach to the correction of this common disorder.

Conflict of interest statement. None.

	References

Top Abstract Introduction Derivation of a new... Discussion Conclusion References

 

1. Adrogue HJ, Madias NE. Hypernatraemia. N Engl J Med (2000) 342:1493–1499.[Free Full Text]
2. Nguyen MK, Kurtz I. New insights into the pathophysiology of the dysnatremias: a quantitative analysis. Am J Physiol Renal Physiol (2004) 287:F172–F180.[Abstract/Free Full Text]
3. Edelman IS, Leibman J, O’Meara MP, et al. Interrelations between serum sodium concentration, serum osmolality and total exchangeable sodium, total exchangeable potassium and total body water. J Clin Invest (1958) 37:1236–1256.[Web of Science][Medline]
4. Kurtz I, Nguyen MK. A simple quantitative approach to analyzing the generation of the dysnatremias. Clin Exp Nephrol (2003) 7:138–143.[CrossRef][Medline]
5. Nguyen MK, Kurtz I. Are the total exchangeable sodium, total exchangeable potassium and total body water the only determinants of the plasma water sodium concentration? Nephrol Dial Transplant (2003) 18:1266–1271.[Free Full Text]
6. Meadow R. Non-accidental salt poisoning. Arch Dis Child (1993) 68:448–452.[Abstract/Free Full Text]
7. Mattar JA, Weil MH, Shubin H, et al. Cardiac arrest in the critically ill. II. Hyperosmolal states following cardiac arrest. Am J Med (1974) 56:162–168.[CrossRef][Web of Science][Medline]
8. Moder KG, Hurley DL. Fatal hypernatraemia from exogenous salt intake: report of a case and review of the literature. Mayo Clin Proc (1990) 65:1587–1594.[Web of Science][Medline]
9. Kahn T. Hypernatraemia with edema. Arch Intern Med (1999) 159:93–98.[Abstract/Free Full Text]
10. Katz M. Hyperglycaemia-induced hyponatremia. Calculation of expected sodium depression. N Engl J Med (1973) 289:843–844.[Web of Science][Medline]
11. Nguyen MK, Kurtz I. Derivation of a new formula for calculating urinary electrolyte-free water clearance based on the Edelman equation. Am J Physiol Renal Physiol (2005) 288:F1–F7.[Abstract/Free Full Text]
12. Watson PE, Watson ID, Batt RD. Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr (1980) 33:27–39.[Abstract/Free Full Text]

Received for publication: 7.11.07
Accepted in revised form: 17.12.07

CiteULike    Connotea    Del.icio.us    What's this?

This article has been cited by other articles:

				T. Ring and C. Overgaard Correcting hypervolaemic hypernatraemia Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3366 - 3366. [Full Text] [PDF]

				M. K. Nguyen and I. Kurtz Reply Nephrol. Dial. Transplant., October 1, 2008; 23(10): 3367 - 3368. [Full Text] [PDF]

This Article Abstract FREE Full Text (PDF) All Versions of this Article: 23/7/2223    most recent gfm932v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Archive Download to citation manager Request Permissions Disclaimer Google Scholar Articles by Nguyen, M. K. Articles by Kurtz, I. Search for Related Content PubMed PubMed Citation Articles by Nguyen, M. K. Articles by Kurtz, I. Social Bookmarking          What's this?

Online ISSN 1460-2385 - Print ISSN 0931-0509

Copyright © 2009 European Renal Association - European Dialysis and Transplant Assoc

Oxford Journals Oxford University Press

• Site Map
• Privacy Policy
• Frequently Asked Questions

Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan American National Biography Booksellers' Information Service Children's Fiction and Poetry Children's Reference Corporate & Special Sales Dictionaries Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks Humanities International Education Unit Law Medicine Music Online Products Oxford English Dictionary Reference Rights and Permissions Science School Books Social Sciences Very Short Introductions World's Classics