Improving the Clinical Management of

Hypernatremic Dehydration Observations from


Study of 67 Infants with This Disorder

Warren Rosenfeld, M.D., Guillermo Lopez de Romana, M.D., Ronald Kleinman, M.D.,

Laurence Finberg, M.D.


ORIGINAL DESCRIPTION hypernatremic dehydration over 25 years ago, our understanding of the pathogenesis and therapy of hypernatremia has led to a great reduction in the morbidity and mortality associated with this disorder. The unique fluid and osmolar changes make this entity more difficult to recognize and treat clinically than the more common isotonic dehydration. In hypernatremic dehydration, the loss of hypotonic fluids from the extracellular space results in a relative rise in extracellular ions (Fig. 1 }. ’ Sodium is the main extracellular cation, and serum sodium concentrations may exceed normal limits of 150 mEq/L. Under these circumstances, extracellular osmolality will also exceed normal (>300 m~srnlL) and an osmotic gradient across cell membranes will occur. Homeostasis requires that the osmolalities on both sides of the cell membrane be equal. Since sodium cannot cross cell membranes freely, the osmotic equilibrium is preserved by the movement of water from


Department of Pediatrics, Montefiore and Medical Center, and The Albert Einstein College of Medicine, 111 East 210th Street, The Bronx, New York 10467. Correspondence to: Warren N. Rosenfeld, M.D., Department of Pediatrics, University of Kansas Medical Center, 39th and Rainbow Boulevard, Kansas City, Kansas 66103. From The

both the intracellular and extracellular fluid volumes leading to increased osmolalities in both. In isotonic dehydration, loss of isotonic fluid from the extracellular space results in no changes in extracellular sodium or osmolality and therefore no major shifts of intracellular water occurs. Hence, treatment of isotonic dehydration requires replacement of extracellular fluid and electrolytes. In contrast, the unique shifts of hypernatremic dehydration require specialized fluid and electrolyte replacement to correct both intracellular and extracellular losses. When these losses

calculated improperly or replaced too rapidly the intracellular space may swell, lead-


ing to significant complications.

To evaluate the effectiveness of a therapeutic regimen designed to meet these needs, we retrospectively reviewed the charts of 67 patients with hypernatremic dehydration secondary to diarrheal disease. This study re-

affirmed many previous observations, revealed several new problems and confirmed a simple effective mode of therapy.


Patients ,and Methods The charts of all patients admitted to the Pediatric Service of the Nlontefiore Hospital and Medical Center with a diagnosis of dehy-


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FIG. L Relative Huid and

electrolyte losses in isotonic and hypematremic dehydration. In hypernatremic dehydration both extracellular fluid

(ECF) and

intracellular Huid (ICF) have decreased volumes and increased osmoialities.


retrospectively reviewed. Any admission diagnosis of dehypatient dration secondary to diarrheal disease based on the clinical impression of the admitting physician and an admission sodium concentration of 2t 150 mEq/L was included in this survey. Sixty-seven patients met these criteria. The Montefiore Hospital and Medical Center’s Pediatric Service encompasses two major hospitals in the Bronx and provides medical care to patients from a wide spectrum of were



social, economic and educational back-

grounds. This spectrum ranges poverty stricken South Bronx to

from the the more affluent suburbs of lower Westchester. All patients were examined initially by an admitting residents and intern. Determinations performed on serum obtained at admission included electrolytes (Na’, CI-) in 67/67 patients, Urea N and COg content in 66/67 patients, glucose in 44/67, and Calcium in I81f~7-utilizin~ the standard methods used in our previous reports.’ .


Epidemiology In the

population surveyed, hypernatremic dehydration appeared to be a winter phenomenon. During the 3-year period investigated, 58 per cent (39/67) patients were admitted during January and February and 73 per cent (49/67) during December, January, and

February (Fig. 2). In these winter months, hypernatremic dehydration accounted for 63 per cent (50/79) of all admissions for dehydration. For each year, however, hypernatremia accounted for an average of 25 per (67/268) of all dehydrated patients who required admission.




Hypernatremia dehydration occurred primarily in young patients. All children found in this survey were less than 4 years of age. Eighty-five per cent (57/67) Nyere less than 12 months of age and 60 per cent (40/67) were 0



6 months old. most


instances, the symptoms began

admission. The first fever in 31 patients, diarrhea in 17, and upper respiratory infection in 14. Of significance, 82 per cent (55/67) of patients had had vomiting or diarrhea for more than 48 hours prior to admission. Among those with vomiting and diarrhea, 65 per cent (36/55) gave a history of total cessation of food and liquids prior to admission. Fever (>~8’.5°C) occurred in 64 per cent (43/67) of all patients prior to admission. Environmental factors such as diet and housing may also play a role in the development of hypernatremia. In 10 per cent (7/67) of the cases, a history of inappropriate (high) intake of solute was obtained. Three patients received boiled skimmed milk,

days prior reported symptoms




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one an

improperly mixed electrolyte solution,

and three were fed regular (high solute) diets throughout the course of the diarrheal disease. A contributory factor is the steam heating systems used in the northeastern United States, which results in low ambient humidity in most homes. This can stimulate water losses from both the skin and respiratory tract and thereby increase the risk of ’

hypernatremia. Clinical Features

Classically, patients with hypernatremic dehydration have minimal signs of decreased intravascular volume, a predominance of central nervous system symptoms and warm, 2 doughy, or velvety skin. Although many of our patients had these findings on admission, a significant number of exceptions did occur. Forty-two per cent (28/67) demonstrated signs of impending intravascular depletion (tachycardia, decreased pulses, and blood pressure and shock). This could be accounted for by the severe degree of. dehydration (or more accurately, the water loss). The degree of water loss could be estimated retrospectively by the weight gain during rehydration. Eight pa.


tients were deemed 15 per cent dehydrated, and 36 were, deemed 10 per cent dehydrated. Water loss of this magnitude can significantly reduce both the extracellular and the intracellular space, leading to signs of intravascular depletion. Only 1 in 3 of the patients were thought to have velvety or doughy skin plus irritability. These signs, nonetheless, are highly

suggestive of hypernatremic dehydration and should alert any examiner to this possibility.

suggestive sign is a known signifiweight loss (greater than 10 per cent) in a patient whose clinical appearance does not indicate such an extreme degree of dehydration.

Another cant

Laboratory Results The admission laboratory values varied wisely and several significant new observations were noted (Fig. 3). The severe sodium concentrations ranged from 150 to 173 mEq/L. The increased osmolality secondary to elevated sodium concentrations was enhanced by significant elevations in glucose concentration in a substantial number of the infants who were tested. Admission glucose values were obtained in only 44 of 67 patients, but in 26 of the 44 these values were elevated ~> 13a mg~c) (Fig. 3). Exceedingly high levels were found in the patients who were the most severely dehydrated. It is therefore advisable to routinely obtain blood glucose values on admission in suspected cases. This phenomenon may be an important consideration in therapy, as discussed below. Measurement of several other parameters may also demonstrate a relatively severe degree of hypernatremic dehydration. Values for Urea N analyses ranged- from 4 to 114 mg/100 ml (Fig. 3). The degree of acidemia, as indicated by reduced CO~ content, is also illustrated in Figure 3. Twenty-seven per cent of patients had Gt3~ content less than 10 mEq/L; 50 per’ cent were 10 to 16.9; and 23 per cent were above 17 mEq/L. In this series, total serum calcium levels were obtained on 18 patients on admission. The level was down moderately (less than 9 mg%) in 4 of the 18 patients, and was

FiG. 2. Distribution of admissions by months. Hy-

pernatremic dehydration had a striking winter incidence ’

’in this series of

patient studies.


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FIG. 3.


Distribution of values on ad-

mission as encountered in 67 patients.

below ,


7 mg/100



ml in 1 patient. admission.



The Dilemma of Therapy The therapy employed follows the principles of therapy previously outlined by US.3 Proper fluid therapy can be calculated by considering three areas: 1) past loss of water and electrolytes 2) daily fluid and electrolyte requirements and 3) ongoing losses. The physiologic dilemma that arises in the management of hypernatremia is to safely replace losses of large amounts of water but of relatively smaller amounts of electrolyte. The intravascular space may be expanded too rapidly with hypotonic fluids; the rapid drop in extracellular fluid. osmolality will create an osmotic gradient across cell membranes. Consequently, water will rapidly enter the cells and cause them to swell. In most tissues this is of no consequence, but in the brain the swelling may have severe side effects.3-5 Recognition. The first step in specific treatment is the early recognition of the disturbance so that it will be treated properly and the estimate of water loss will not be based solely on signs of extracellular fluid loss. Emergency Therapy. Next is the determination of circulatory compromise which, when present, requires emergency management. When intravascular depletion is severe, which may occur with greater than 10 per cent loss of body weight, a relatively rapid intravenous

infusion of a solution containing 4 to 5 per albumin as single donor plasma, whole blood or 5 per cent albumin should be administered. The solution should be calculated as 20 ml/kg of the dehydrated weight and a over 30-minute interval. given Anuria. When signs of intravascular depletion are not present, the deficit will usually be less than 10 per cent. With these infants, no emergency therapy is required; in fact rapid administration of fluid is contraindicated.~ An exception may arise when a dehydrated patient has also been anuric for more than several hours. In this situation, fluid may be given at a faster rate (25 to 50 ml/kg) for 4 to 5 hours until urine output begins. The solution used in this situation contained 75 to 80 mEq/L of sodium in 5 per cent glucose and no potassium. Anion content should vary according to the source of loss. With diarrhea, one-quarter to one-third of the anion should be given as a base and the cent


chloride. Replacement. In the absence of shock or anuria, or after a rapid infusion as outlined above, the fluid for repletion and maintenance is given slowly. Forty-eight hours has been selected as an appropriate length of time for repletion in hypernatremic dehydration. During this 48 hour period, the volume of fluid given is accounted for in terms of estimated deficit incurred, daily requirements, and ongoing abnormal losses. Deficit fluid is calculated from known weight loss as



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clinical presentation. If an emergency &dquo;push&dquo; of fluid ~z.~., 4 to 5 per cent albumin) is given, the amount is subtracted from the deficit fraction. Daily fluid requirements are calculated from an estimate of calories metabolized. Added to these daily re-


unique shifts of hypernatremic dehydration require specialized fluid and electrolyte replacement to correct both


intracellular and extracellular losses.

quirements are ongoing losses, some insensible (sweating, tachypnea, fever) and others grossly visible (continued vomiting and stool losses). To this volume electrolytes are added, usually resulting in a concentration of 25 to 40 mEq/L of sodium. Since these patients may or may not have a deficit of sodium’-’

prefer to avoid overexpansion of the extracellular space early in therapy. The solution also contains 2.5 to 5 per cent glucose. We have come to realize that an extremely important safeguard is to add maximum safe amounts of potassium (40 mEq/L) to provide intracellular ion along with water for cell rehydration. Potassium is not added until urine formation has been demonstrated. Again, the anion is in physiologic proportion with 2/3 to ~/4 chloride and to 1/4 base

Four patients had convulsions. One of these patients (6 weeks of age) convulsed on his 5th day of hospitalization, 2 days after rehydration. At that time he had a total calcium level of 5.2 mg/100 ml (ionized Ca++=2

mg%) and




having early

rickets unrelated either to his dehydration or his therapy. Another patient with 15 per cent weight loss had, on admission, a right focal seizure and respiratory arrest, and was found to have a left subdural effusion with bloody cerebrospinal fluid. Subsequently he had persistent right-sided neurologic deficits. A third patient, the only one with a convulsion apparently related to the therapy, developed a generalized convulsion 30 hours after hospitalization. Subsequently, it was found that the patient’s intravenous fluids had been allowed to run in at a significantly greater rate than intended. The 2 fatalities in the series were related to the severity of the primary illness.






previously mentioned, a critical factor in rehydrating the hypernatremic patient is the As

of fluid administration. This rate in our management is constant for each of the first 48 hours (exceptions noted above), with the total volume being divided over this period. If oral fluid is taken during this interval, the amount is subtracted from parenteral fluid totals.



Following the guidelines previously presented in greater detail,4 we have encountered

problems while rehydrating hypernatremic patients. Of the total of 67 patients, complications were seen in only 5 with 2 fatalities. Complications seemed ascribable to therapy in only 1 of the 5 patients. few

Discussion The characteristic physiologic changes which occur in hypernatremic dehydration are potentially hazardous. Prompt recognition of these changes and an understanding of the pathophysiology are a prerequisite for successful treatment. In isotonic dehydration, in which fluid and electrolytes are lost primarily from the extracellular spaces and intracellular volume is maintained, one may judge the severity of dehydration by signs of intravascular and interstitial depletion (e.g, , tachycardia, poor skin elasticity, and turgor). In hypernatremic dehydration, since water is lost in excess of electrolyte, the body fluid osmolality rises. As the sodium concentration of the extracellular fluid increases, most of the &dquo;excess&dquo; sodium remains extracellular, drawing water along an osmotic gradient from within the cells. This shift of water leads to intracellular dehydration with relative preservation of the extracellular fluid. This basic distinction has numerous consequences. When the changes occur rapidly, there are important implications for the brain. The anatomic and physiologic boundary between capillaries and interstitial fluid in the


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brain (the blood-brain barrier) consists of capillaries with tight junctions, unlike capillaries in other organs.’ This interface, while permitting essentially instantaneous passage of water, allows for a much slower interchange of solute including small ions such as sodium.


dehydration progress rapidly. The difficulty in the recognition of dehydration in hypernatremia by parents and medical personnel emphasizes the necessity for constant of this disturbance in order to dehydration at less significant levels. The significant factor of hyperglycemia has




Classically, patients with hypernatremic dehydration have minimal signs of

cause an even

steep. This would be of little consequence if it were not for the rigid structure of the cranium which makes either brain swelling or shrinkage a feared complication. The increased morbidity and mortality in hypernatremia and its therapy can be accounted for mainly by these effects on the brain. The regimen set forth here appears to be at least ;

higher physiologically signifi-

during rehydration. Consequently, we no insulin be given to patients with hypernatremic dehydration secondary to diarrheal disease even when concomitant hyperglycemia is severe. The paucity of untoward results attests to a successful mode of therapy in these patients. Of the 4 patients who had convulsions, only 1 can be accounted for by a therapy failure and that one occurred through error in technique. When compared to previous experiences, where 25 to 33 per cent of patients had seizures during rehydration, 2,11 these immediate results

seem better. will be needed to Long follow-up with the high compare neurologic sequelae incidence in other reports.10



Conclusions and



1. Hypernatremia in recent experience was primarily a wintertime physiologic disturbance seen especially in young infants.

needed before conclusions may be drawn. The high percentage of our patients with greater than 10 per cent weight loss (63 per cent; (44/67) is not surprising for several reasons. In any series in which 57 of 67 patients are under 1 year of age, water loss

days of illness prior to the development of hypernatremia. Fever, vomiting, diarrhea and anorexia were prominent features of what seems to be a respiratory viral illness. Cessation of intake, as previously noted, usually occurred abruptly.

patients . in our community. These epidemiologic coincidences provide for interesting speculation but further analysis is


recommend that

improve the therapeutic outcome. Recognition of hypernatremia is a prerequisite for proper therapy. Since the majority of cases occurred during the winter months, the physician should consider the diagnosis of hypernatremia in patients with dehydration seen during this season. In temperate climates, the norman high solute diet of our culture, the increases in respiratory rate and

analyses are



cessation of oral intake, and the low humidity in heated homes during the winter, all predispose to excess water loss and the development of hypernatremia. An interesting aspect of the incidence of these hypernatremic &dquo;epidemics&dquo; has been the stimultaneous outbreaks of RS virus among


than will sodium concentration alone. The exact mechanism of the defect of glucose metabolism is unclear at present, but idiogenic osmols appear in cerebral cells during rapid reduction of blood sugar levels. Since idiogenic osmols have been demonstrated in hypernatremia,’ rapid reduction of glucose levels by insulin may result in a rapid decrease in extracellular osmolality and contribute to cerebral cant

During the process of rehydration, brain swelling will occur if the water concentration gradient (from plasma to brain) becomes


important as

performed.8 Elevations of glucose (greater than 130 mg%) in 59 per cent of patients who had levels measured on admission can

decreased intravascular volume, a predominance of central nervous system symptoms and warm, doughy, or velvety skin.



2. The histories often included several


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degree of dehydration was often severe, requiring emergency therapy. Physical findings of irritability, velvety or doughy skin and known weight loss greater than that expected from clinical signs of intracellular fluid depletion should alert the physician to the possibility of hypernatremia. 3. The

All children found in this survey less than 4 years of age.


4. Successful management calls for a careful balance between restoration of the intracellular fluid without too rapid a repletion of the extracellular fluid, in order to prevent cerebral swelling or undue edema. Shock and anuria require more immediate aggressive treatment therapy, but a good outcome can be anticipated with the regimen here described, with corrections spread over a 48 hour period. 5. Hyperglycemia may be found in a substantial number of patients. Tentatively, on theoretical grounds, we suggest that insulin may be contraindicated. In our patients, without use of insulin, recovery was rapid and


References 1.

Finberg, L.: Pathogenesis

of lesions in the


system in hypernatremic states. 1. Clinical observa-

tions of infants. Pediatrics 23: 40, 1959. J. E., and Cohen, D. L.: Understanding and managing hypernatremic dehydration. Pediatr. Clin. North Am. 21: 435, 1974. 3. Finberg, L.: Hypernatremic Dehydration. Advances in pediatrics. Chicago, Yearbook Medical Pub16: 325, 1969. lishers, Inc. 4. Weil, W. B., and Wallace, W. M.: Hypertonic dehydration in infancy. Pediatrics 17: 171, 1956. 5. Finberg, L.: Diarrheal dehydration. In The Body Fluids in Pediatrics. Winters, R., Ed. Little, Brown and Company, Boston, 1973. 6. Darrow, D. C., and Welsh, J. S.: Recent experience in the treatment of diarrhea in infants. J. Pediatr. 56: 204, 1960. 7. Reese, T. S., and Karnovsky, M. J.: Fine structural localization of a blood-brain barrier to 207, 1967. exogenous peroxidase. J. Cell Biol. 34: 8. Stevenson, R. E., and Bowyer, F. P.: Hyperglycemia with hyperosmolal dehydration in non-diabetic infants. J. Pediatr. 77: 818, 1970. 9. Arieff, A. I., and Kleeman, C. R.: Studies on mechanisms of cerebral edema in diabetic comas. Effects of hyperglycemia and rapid lowering of plasma glucose in normal rabbits. J. Clin. Invest. 52: 571, 1973. 10. Macaulay, D., and Watson, M.: Hypernatremia in infants as a cause of brain damage. Arch. Dis. Child. 42: 485, 1967. 11. Bruck, E., Abal, G., and Aceto, T., Jr.: Therapy of infants with hypertonic dehydration due to diarrhea. Am. J. Dis. Child. 115: 281, 1968. 2. Haddow,


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Improving the clinical management of hypernatremic dehydration. Observations from a study of 67 infants with this disorder.

CLINICAL REVIEW Improving the Clinical Management of Hypernatremic Dehydration Observations from a Study of 67 Infants with This Disorder Warren...
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