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Understanding and Managing Hypernatremic Dehydration
Symposium on Recent Clinical Advances
Understanding and Managing Hypernatremic Dehydration James E. Haddow, M.D.,* and DanielL. Cohen, M.D.**
Hypernatremic dehydration in infancy and early childhood (serum sodium greater than 150 mEq. per liter) is a serious problem, and effective management requires a thorough understanding of the pathophysiology of this disorder. Improper fluid therapy may be associated with a significant mortality and, more commonly, with seizures1 which may result in long term neurologic sequelae. 11 Recognition of hypernatremic dehydration as a distinct clinical and biological entity took place 60 years ago when Salge reported his observations.12 As serum electrolyte determinations became more available, there gradually emerged an appreciation that this problem occurred regularly; and at present it is known that approximately 10 to 20 per cent of infants hospitalized with dehydration will have serum sodium values in excess of 150 mEq. per liter. During the past 25 years much has been written on this subject, and an understanding of the problem has evolved which allows for more successful management.
CLINICAL PRESENTATION Ordinarily, historical information obtained from parents of a child with hypernatremic dehydration reveals nothing characteristic. The specific exception to this statement would arise if the child's diet were inappropriately high in salt or solute. 2 • 4 Although no such insult can be found to explain most cases of hypernatremic dehydration, there are enough exceptions to make detailed history of the dietary intake mandatory whenever a child presents with gastroenteritis. The commonest examples of excessive solute load involve solutions of sugar-salt-w~ter which have been wrongly mixed because amounts of added sugar and salt have been ''Associate Professor of Pediatrics, Boston University School of Medicine, and Director, Pediatric Endocrinology, Department of Pediatrics, Boston City Hospital, Boston, Massachusetts *'''Senior Assistant Resident, Children's Hospital Medical Center, Boston; Formerly Junior Assistant Resident, Department of Pediatrics, Boston City Hospital, Boston, Massachusetts Supported in part by Hood Foundation Grant No. 3132-5.
Pediatric Clinics of North America- Vol. 21, No.2, May 1974
435
436
]AMES
E.
HADDOW AND DANIEL
L.
COHEN
reversed, powdered formulas which when hydrated are made too concentrated, and boiled skim milk which is boiled to the point where significant concentration has occurred. When an infant with hypernatremic dehydration presents to a physician, he will usually display alternating periods of lethargy and irritability. Physical examination may reveal "doughy" skin over the abdomen, and the experienced observer will be able to predict elevated serum sodium with a high degree of accuracy. There can be no substitute, however, for serum electrolyte values, and they should be measured in any infant requiring hospitalization for dehydration. Rapid breathing resulting from acidosis is frequently seen, and this may be disproportionately severe in relation to the clinically determined dehydration. The classic clinical signs used to judge dehydration (skin turgor and tenting, dryness of the mouth, mottling of skin, cool extremities, unstable vital signs, etc.) are not as reliable an index of dehydration in the presence of hypernatremia because the extracellular fluid compartment is relatively better preserved than in isonatremic dehydration. Concomitantly there are relatively greater water and solute losses from the intracellular compartment. As a result, the physical examination often results in underestimation of the degree of dehydration, except when the infant presents in shock or peripheral vascular collapse. In the absence of a reliable documentation of weight loss the degree of dehydration may be predicted with reasonable accuracy if 3 to 5 per cent loss of body weight is added to the loss calculated from physical findings. It is common for blood sugar to be elevated when measured as part of the initial blood sample. Even though the levels are frequently in excess of 200 mg. per dl., there is no need to treat with insulin, and the values rapidly become normal during rehydration. Lumbar puncture is often performed when an infant presents with hypernatremic dehydration, because of the irritability and lethargy. Cerebrospinal fluid protein is usually elevated, and this by itself should not be considered worrisome. On admission or in the first day of therapy the infant may be noted to have hypocalcemia. This may persist for several days if calcium is not added to the intravenous solution and in an occasional child may produce symptoms late in the course of rehydration. The bases for these biochemical abnormalities are not known.
PATHOGENESIS Any child with gastroenteritis will lose proportionately more water than sodium. Diarrheal stool water losses average 50 to 60 mEq. per liter of sodium although the range is wide. 10 Skin losses are approximately 40 mEq. of sodium per liter, and water lost in respiration is virtually sodiumfree. Therefore in diarrheal dehydration water is always lost in excess of sodium. Compensatory efforts on the part of the organism are directed primarily at preserving extracellular fluid volume and include concentration of urine to conserve water, movement of water from the intracellular to the extracellular compartment, and, in most cases, thirst. Usually
UNDERSTANDING AND MANAGING HYPERNATREMIC DEHYDRATION
437
these efforts are at least partially successful and serum sodium remains within normal range. It is rare for hypernatremic dehydration to develop after the second year of life. This problem develops in significant numbers of children under one year of age, however, and it is important to consider possible causes for their greater susceptibility. Empirically their compensatory mechanisms seem to function less efficiently. Is this because they are simply unable to express verbally their need to drink, or to walk to a faucet? Is it also possible that they may lose acutely large volumes of hypotonic stool in combination with anorexia? Or is it possible that there is an increased endogenous sodium load to the extracellular fluid secondary to mobilization from bone stores?5 • 13 Any of these possibilities may well occur in a given infant to set the stage for hypernatremia. It is easier to understand how hypernatremic dehydration occurs when a formula inappropriately high in solute is given. Under such stress, more sodium may be absorbed and, also, the irritating highly osmotic formula may cause more water to be lost from the extracellular compartment into the gastrointestinal tract. As the clinical condition deteriorates and acidosis with its attendant increased respiratory water losses becomes an added problem, it is easy to imagine hypernatremia being further intensified. In the presence of hypernatremia, the integrity of the extracellular fluid compartment is maintained at the expense of the intracellular compartment. The presence of increased numbers of nondiffusable ions or osmols within the extracellular compartment creates a concentration gradient favoring the diffusion of water from the intracellular fluid compartment to the extracellular compartment with resultant cellular desiccation. Hence the extracellular compartment is relatively better preserved and the usual physical findings of dehydration do not appear until the body has sustained a greater depletion of water. Preservation of the extracellular fluid compartment is not as efficient in isotonic or hypotonic dehydration; hence physical signs appear earlier in the course of dehydration. Metabolic acidosis is a frequent if not universal accompaniment of diarrheal dehydration in infants, and those with hypernatremia appear generally more severely acidotic at any given level of dehydration. Several factors are present in any infant with diarrhea and dehydration which may predispose to acidosis. First there is a fall in the glomerular filtration rate which results in lower hydrogen ion excretion (recent work suggests that this may not play as important a role in'producing acidosis as has been presumed in the past). 7 Second, the acute illness precipitates tissue catabolism. This gives rise to ketone bodies and increased production of non-volatile acids. Third, in the presence of diarrhea, there is a significant loss of bicarbonate in the stool. This is thought to occur as a buffer against increased ;gut lactate production arising from bacterial fermentation of unabsorbed carbohydrates. 14 • 15 Fourth, when dehydration is severe enough to compromise oxygen availability to tissues, increased lactic acid production will further add to the acid load. The foregoing factors leading to metabolic acidosis are applicable to any individual with gastroenteritis and dehydration. The infant with
438
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E.
HADDOW AND DANIEL
L.
CoHEN
hypernatremia has an added burden because his tissue buffers (notably hemoglobin) dissociate in response to the hyperosmolar situation and are not available to buffer acids. 16 Furthermore, there is, at least inferentially, damage to the intracellular compartment more than in other dehydration states which could add to the endogenous acid load. This damage is reflected by the presence of "idiogenic osmols" intracellularly,3 so called because they have not yet been characterized but are thought to result from fragmentation of normal intracellular compounds. It is these "idiogenic osmols" which have been implicated also in the inappropriate intracellular brain swelling leading to seizures during rehydration. Seizures are frequent in the course of rehydration of hypernatremic infants. In the past approximately one third of such patients convulsed within the first 2 days of treatment. These seizures are a direct result of cerebral edema, and this edema appears even before the patient has been fully rehydrated. Animal studies by Hogen9 have demonstrated the increased brain water present at the time of seizures but have failed to identify the osmotically active agent responsible for attracting water to the intracellular compartment. While it would be worthwhile to know the agent responsible, the most important feature of seizure production remains the inappropriately high brain water. Anticipation of seizures is accomplished by close monitoring of the infant for signs of increasing irritability and for an increase in blood pressure8 (a reflection of increasing intracranial pressure). These signs generally occur over a 1 to 3 hour period, thus allowing slowing of fluid administration to prevent seizures. In the event that seizures do occur treatment should be directed at rapid removal of intracellular brain water. Infusion of hypertonic saline might appear contradictory but it produces a prompt decompression of the brain, and seizures are immediately controlled. Mannitol has a similar beneficial effect.
THERAPY AND MANAGEMENT Of equal importance with specific intravenous fluid formulas is an overall plan designed to monitor the patient's progress. Even before initial laboratory values have been obtained and the problem of hypernatremia has been defined the physician must direct his attention primarily to the immediate care of the patient. The management of shock and vascular collapse takes precedence over pending laboratory values. It cannot be emphasized too much that the patient's clinical improvement (as measured objectively) determines the success or-failure of any fluid and electrolyte regimen. Laboratory values become of secondary importance because they define the state of the patient after the fact. Finally, the physician must not become a slave to his original fluid plan, but must be prepared to vary it according to the patient's progress or lack of progress. Several parameters may be used for patient monitoring, and both nurse and doctor will use them and interpret them. Weight on admission must be compared with subsequent weights which should be obtained at
UNDERSTANDING AND MANAGING HYPERNATREMIC DEHYDRATION
439
6 hour intervals, and a judgment made as to whether hydration is progressing rapidly enough or too rapidly. In general it is unwise to allow hypernatremic infants to gain back more than one half to two thirds of their estimated weight loss in the first 24 hours, and if weight is being gained too fast, fluid administration should be slowed. If weight gain is too slow, then fluid- administration should be increased, and possible sources of ongoing fluid losses explored. Pulse, .respiration, and blood pressure measurements should be determined at hourly intervals. They are easily done and, particularly in the early stages of rehydration, give valuable information as to whether progress is being made. Initially, the pulse rate may be increased because of diminished circulatory volume, and its return to normal and stabilization are important to document. Respirations are often increased at first from metabolic acidosis, and the success of managing that problem will be reflected directly with the fall to normal of the respiratory rate. Blood pressure is particularly important in managing hypernatremic infants. If severe extracellular compromise is present at the beginning, blood pressure may be low and reflect frank shock; or there may be a slightly elevated pressure, reflecting a final homeostatic effort to preserve circulatory integrity. As with other vital signs, the normalization and stabilization of blood pressure represents an important measurement. Of further importance is the rise in blood pressure which occurs when fluid is being given too rapidly and when brain swelling is occurring. A rise in both systolic and diastolic blood pressure takes place over a relatively short time period and is one good parameter whereby seizures can be anticipated and avoided· by slowing fluid administration. Blood pressure should be measured every hour, and specific orders should be written so that the physician will be notified if an elevation occurs. State of consciousness and degree of irritability should be recorded with other measurements at hourly intervals. When present, the initial lethargy and irritability should disappear in the early hours of treatment. If and when irritability does reappear, it is likely to be in conjunction with rising blood pressure and heralds the impending onset of seizures. Other observations of the infant's condition should also be made systematically. The character of the skin is very important. Mottling and slow capillary filling are signs of peripheral vascular instability and they should rapidly be corrected. Similarly, tenting of the skin, if present, will diminish as the extracellular fluid compartment is expanded. If edema appears in the course of treatment, fluid administration is much too rapid and must be promptly readjusted. Once the infant is found to be hypernatremic, the planning of fluid administration requires only that readjustments in rate of administration be made according to the guidelines just discussed. As with any acutely dehydrated infant water is calculated to provide adequate maintenance and half replacement of acute losses during the first 24 hours. (The first 24 hour water calculation includes, of course, the volume of initial hydrating solutions.) Acute potassium losses have been found to be similar in all forms of gastroenteritis, and so maintenance and replacement potassium are also given according to the usual guidelines. Potassium is
440
JAMES
E.
HADDOW AND DANIEL
L.
COHEN
not begun until after the initial stage of hydration has been judged successful (i.e., shock corrected and urine output established) and should not exceed 40 mEq. per liter in an intravenous solution. Important restrictions exist in planning for sodium administration to hypernatremic infants, because it has been convincingly shown that the likelihood of developing cerebral edema and seizures increases steadily as the concentration of sodium falls progressively below 50 mEq. per liter in hydrating solutions. For this reason sodium concentration in the intravenous fluid must take precedence over the usual considerations of maintenance and replacement. It is recommended that all hydrating solutions employed in managing hypernatremically dehydrated patients contain between 50 mEq. and 75 mEq. of sodium per liter (after initial hydration with normal saline or Ringer's lactate). While it may appear inconsistent to give this much sodium to an individual whose serum sodium is already high, it is important to appreciate that in most instances total body sodium is still depleted. The major concern after extracellular compromise has been corrected is the prevention of seizures during the remainder of rehydration. The sodium concentration of the intravenous fluid is a major factor in preventing seizures. An additional electrolyte to be considered in the present problem is calcium. It is commonly observed that serum calcium concentrations are low either on admission or during the first day of therapy. On occasion, hypocalcemia persists and the patient becomes symptomatic on the fourth or fifth day of management. It is reasonable to add calcium to the fluid regimen, and 16 to 20 mg. of elemental calcium per kg. of body weight for young children may be added to each day's intravenous fluids with safety. A fluid regimen for such an infant would begin with an acute infusion of normal saline or Ringer's lactate over the first 2 hours. (A reasonable rate would be 20 ml. per kg. per hr.) During that time calculations would be made for the first 24 hours' fluid volume allotment. Then, following the initial infusion, the remainder of the day's fluid would be evenly spaced over the remainder of the 24 hours. That fluid would consist of sodium, 50 to 75 mEq. per liter; potassium, 30 to 40 mEq. per liter; and calcium, 5 to 10 mEq. per liter. During the second 24 hours, maintenance fluid volume would be combined with the remainder of replacement volume and the fluid composition would remain the same as the first day. Once the diagnosis ofhypernatremia has been established and appropriate fluids have been begun, then a chart can be made which contains the vital signs, weight, and other measurements to be used in following the infant's progress. With proper monitoring and interpretation of such recordings, a smooth recovery can be anticipated, and the serum sodium will gradually fall to normal over the first few days.
REFERENCES 1. Bruck, E., Abal, G., and Aceto, T., Jr.: Therapy of infants with hypertonic dehydration due to diarrhea. Amer. J. Dis. Child., 115:281-301, 1968.
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2. Colle, E., Ayoub, E., and Raile, R.: Hypertonic dehydration (hypernatremia): The role of feedings high in solutes. Pediatrics, 22:5-12, 1958. 3. Clark, W. M.: Topics in Physical Chemistry. Baltimore, Williams and Wilkins Co., 1952, p. 237. 4. Finberg, L., Kiley, J., and Luttrell, C. N.: Mass accidental salt poisoning in infancy. ].A.M.A., 184:187, 1963. 5. Forbes, G. B., and McCoord, A.: Bone sodium as a function of serum sodium in rats. Amer. J. Physiol., 209:830-834, 1965. 6. Gall, D. G., and Haddow, J. E.: Effects of acute hypernatraemia. Lancet, 2:783, 1969. 7. Hill, L. L., Morris, C. R., and Williams, R. L.: Role of tissue hypoxia and defective renal acid excretion in the development of acidosis in infantile diarrhea. Pediatrics, 4 7:246-253, 1971. 8. Hogan, G. R., Gill, S. R., Master, S., et al.: On the pathogenesis of seizures occurring during rehydration in chronic hypertonic dehydration. Trans. Amer. Neurol. Assoc., 90:257260, 1965. 9. McDowell, M. E., Wolf, A. V., and Steer, 0.: Osmotic volumes of distribution. Ideogenic changes in osmotic pressure associated with administration of hypertonic solutions. Amer. J. Physiol., 180:545, 1955. 10. Mahalanabis, D., Wallace, C. K., Kallen, R. J., et al.: Water and electrolyte losses due to cholera in infants and small children: A recovery balance study. Pediatrics, 45:374, 1970. 11. Morris-Jones, P. H., Houston, I. B., and Evans, R. C.: Prognosis of the neurological complications of acute hypernatremia. Lancet, 2:1385-1389, 1967. 12. Salge, B.: Die physikalisehen Erscheinungen des Elutes bein gesunden und kuanken Sangling. Ztschr. Kinderh., 1:126, 1911. 13. Swan, R. C., and Pitts, R. F.: Neutralization of infused acid by nephrectomized dogs. J. Clin. Invest., 34:205-212, 1955. 14. Teree, T. M., Mirabal-Font, E., Ortiz, A., et al.: Stool losses and acidosis in diarrheal disease of infancy. Pediatrics, 36:704-712, 1965. 15. Torres-Pinedo, R., Lavastida, M., Rivera, C. L., et al.: Studies on infant diarrhea. I. A comparison of the effects of milk feeding and intravenous therapy upon the composition and volume of the stool and urine. J. Clin. Invest., 43:469-480, 1966. 16. Winters, W. W., Seaglione, P. R., Nahas, G. G., et al.: The mechanisms of acidosis produced by hyperosmotic infusions. J. Clin. Invest., 45:647-658, 1964. Department of Pediatrics Boston City Hospital 818 Harrison Avenue Boston, Massachusetts 02118
Understanding and Managing Hypernatremic Dehydration James E. Haddow, M.D.,* and DanielL. Cohen, M.D.**
Hypernatremic dehydration in infancy and early childhood (serum sodium greater than 150 mEq. per liter) is a serious problem, and effective management requires a thorough understanding of the pathophysiology of this disorder. Improper fluid therapy may be associated with a significant mortality and, more commonly, with seizures1 which may result in long term neurologic sequelae. 11 Recognition of hypernatremic dehydration as a distinct clinical and biological entity took place 60 years ago when Salge reported his observations.12 As serum electrolyte determinations became more available, there gradually emerged an appreciation that this problem occurred regularly; and at present it is known that approximately 10 to 20 per cent of infants hospitalized with dehydration will have serum sodium values in excess of 150 mEq. per liter. During the past 25 years much has been written on this subject, and an understanding of the problem has evolved which allows for more successful management.
CLINICAL PRESENTATION Ordinarily, historical information obtained from parents of a child with hypernatremic dehydration reveals nothing characteristic. The specific exception to this statement would arise if the child's diet were inappropriately high in salt or solute. 2 • 4 Although no such insult can be found to explain most cases of hypernatremic dehydration, there are enough exceptions to make detailed history of the dietary intake mandatory whenever a child presents with gastroenteritis. The commonest examples of excessive solute load involve solutions of sugar-salt-w~ter which have been wrongly mixed because amounts of added sugar and salt have been ''Associate Professor of Pediatrics, Boston University School of Medicine, and Director, Pediatric Endocrinology, Department of Pediatrics, Boston City Hospital, Boston, Massachusetts *'''Senior Assistant Resident, Children's Hospital Medical Center, Boston; Formerly Junior Assistant Resident, Department of Pediatrics, Boston City Hospital, Boston, Massachusetts Supported in part by Hood Foundation Grant No. 3132-5.
Pediatric Clinics of North America- Vol. 21, No.2, May 1974
435
436
]AMES
E.
HADDOW AND DANIEL
L.
COHEN
reversed, powdered formulas which when hydrated are made too concentrated, and boiled skim milk which is boiled to the point where significant concentration has occurred. When an infant with hypernatremic dehydration presents to a physician, he will usually display alternating periods of lethargy and irritability. Physical examination may reveal "doughy" skin over the abdomen, and the experienced observer will be able to predict elevated serum sodium with a high degree of accuracy. There can be no substitute, however, for serum electrolyte values, and they should be measured in any infant requiring hospitalization for dehydration. Rapid breathing resulting from acidosis is frequently seen, and this may be disproportionately severe in relation to the clinically determined dehydration. The classic clinical signs used to judge dehydration (skin turgor and tenting, dryness of the mouth, mottling of skin, cool extremities, unstable vital signs, etc.) are not as reliable an index of dehydration in the presence of hypernatremia because the extracellular fluid compartment is relatively better preserved than in isonatremic dehydration. Concomitantly there are relatively greater water and solute losses from the intracellular compartment. As a result, the physical examination often results in underestimation of the degree of dehydration, except when the infant presents in shock or peripheral vascular collapse. In the absence of a reliable documentation of weight loss the degree of dehydration may be predicted with reasonable accuracy if 3 to 5 per cent loss of body weight is added to the loss calculated from physical findings. It is common for blood sugar to be elevated when measured as part of the initial blood sample. Even though the levels are frequently in excess of 200 mg. per dl., there is no need to treat with insulin, and the values rapidly become normal during rehydration. Lumbar puncture is often performed when an infant presents with hypernatremic dehydration, because of the irritability and lethargy. Cerebrospinal fluid protein is usually elevated, and this by itself should not be considered worrisome. On admission or in the first day of therapy the infant may be noted to have hypocalcemia. This may persist for several days if calcium is not added to the intravenous solution and in an occasional child may produce symptoms late in the course of rehydration. The bases for these biochemical abnormalities are not known.
PATHOGENESIS Any child with gastroenteritis will lose proportionately more water than sodium. Diarrheal stool water losses average 50 to 60 mEq. per liter of sodium although the range is wide. 10 Skin losses are approximately 40 mEq. of sodium per liter, and water lost in respiration is virtually sodiumfree. Therefore in diarrheal dehydration water is always lost in excess of sodium. Compensatory efforts on the part of the organism are directed primarily at preserving extracellular fluid volume and include concentration of urine to conserve water, movement of water from the intracellular to the extracellular compartment, and, in most cases, thirst. Usually
UNDERSTANDING AND MANAGING HYPERNATREMIC DEHYDRATION
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these efforts are at least partially successful and serum sodium remains within normal range. It is rare for hypernatremic dehydration to develop after the second year of life. This problem develops in significant numbers of children under one year of age, however, and it is important to consider possible causes for their greater susceptibility. Empirically their compensatory mechanisms seem to function less efficiently. Is this because they are simply unable to express verbally their need to drink, or to walk to a faucet? Is it also possible that they may lose acutely large volumes of hypotonic stool in combination with anorexia? Or is it possible that there is an increased endogenous sodium load to the extracellular fluid secondary to mobilization from bone stores?5 • 13 Any of these possibilities may well occur in a given infant to set the stage for hypernatremia. It is easier to understand how hypernatremic dehydration occurs when a formula inappropriately high in solute is given. Under such stress, more sodium may be absorbed and, also, the irritating highly osmotic formula may cause more water to be lost from the extracellular compartment into the gastrointestinal tract. As the clinical condition deteriorates and acidosis with its attendant increased respiratory water losses becomes an added problem, it is easy to imagine hypernatremia being further intensified. In the presence of hypernatremia, the integrity of the extracellular fluid compartment is maintained at the expense of the intracellular compartment. The presence of increased numbers of nondiffusable ions or osmols within the extracellular compartment creates a concentration gradient favoring the diffusion of water from the intracellular fluid compartment to the extracellular compartment with resultant cellular desiccation. Hence the extracellular compartment is relatively better preserved and the usual physical findings of dehydration do not appear until the body has sustained a greater depletion of water. Preservation of the extracellular fluid compartment is not as efficient in isotonic or hypotonic dehydration; hence physical signs appear earlier in the course of dehydration. Metabolic acidosis is a frequent if not universal accompaniment of diarrheal dehydration in infants, and those with hypernatremia appear generally more severely acidotic at any given level of dehydration. Several factors are present in any infant with diarrhea and dehydration which may predispose to acidosis. First there is a fall in the glomerular filtration rate which results in lower hydrogen ion excretion (recent work suggests that this may not play as important a role in'producing acidosis as has been presumed in the past). 7 Second, the acute illness precipitates tissue catabolism. This gives rise to ketone bodies and increased production of non-volatile acids. Third, in the presence of diarrhea, there is a significant loss of bicarbonate in the stool. This is thought to occur as a buffer against increased ;gut lactate production arising from bacterial fermentation of unabsorbed carbohydrates. 14 • 15 Fourth, when dehydration is severe enough to compromise oxygen availability to tissues, increased lactic acid production will further add to the acid load. The foregoing factors leading to metabolic acidosis are applicable to any individual with gastroenteritis and dehydration. The infant with
438
]AMES
E.
HADDOW AND DANIEL
L.
CoHEN
hypernatremia has an added burden because his tissue buffers (notably hemoglobin) dissociate in response to the hyperosmolar situation and are not available to buffer acids. 16 Furthermore, there is, at least inferentially, damage to the intracellular compartment more than in other dehydration states which could add to the endogenous acid load. This damage is reflected by the presence of "idiogenic osmols" intracellularly,3 so called because they have not yet been characterized but are thought to result from fragmentation of normal intracellular compounds. It is these "idiogenic osmols" which have been implicated also in the inappropriate intracellular brain swelling leading to seizures during rehydration. Seizures are frequent in the course of rehydration of hypernatremic infants. In the past approximately one third of such patients convulsed within the first 2 days of treatment. These seizures are a direct result of cerebral edema, and this edema appears even before the patient has been fully rehydrated. Animal studies by Hogen9 have demonstrated the increased brain water present at the time of seizures but have failed to identify the osmotically active agent responsible for attracting water to the intracellular compartment. While it would be worthwhile to know the agent responsible, the most important feature of seizure production remains the inappropriately high brain water. Anticipation of seizures is accomplished by close monitoring of the infant for signs of increasing irritability and for an increase in blood pressure8 (a reflection of increasing intracranial pressure). These signs generally occur over a 1 to 3 hour period, thus allowing slowing of fluid administration to prevent seizures. In the event that seizures do occur treatment should be directed at rapid removal of intracellular brain water. Infusion of hypertonic saline might appear contradictory but it produces a prompt decompression of the brain, and seizures are immediately controlled. Mannitol has a similar beneficial effect.
THERAPY AND MANAGEMENT Of equal importance with specific intravenous fluid formulas is an overall plan designed to monitor the patient's progress. Even before initial laboratory values have been obtained and the problem of hypernatremia has been defined the physician must direct his attention primarily to the immediate care of the patient. The management of shock and vascular collapse takes precedence over pending laboratory values. It cannot be emphasized too much that the patient's clinical improvement (as measured objectively) determines the success or-failure of any fluid and electrolyte regimen. Laboratory values become of secondary importance because they define the state of the patient after the fact. Finally, the physician must not become a slave to his original fluid plan, but must be prepared to vary it according to the patient's progress or lack of progress. Several parameters may be used for patient monitoring, and both nurse and doctor will use them and interpret them. Weight on admission must be compared with subsequent weights which should be obtained at
UNDERSTANDING AND MANAGING HYPERNATREMIC DEHYDRATION
439
6 hour intervals, and a judgment made as to whether hydration is progressing rapidly enough or too rapidly. In general it is unwise to allow hypernatremic infants to gain back more than one half to two thirds of their estimated weight loss in the first 24 hours, and if weight is being gained too fast, fluid administration should be slowed. If weight gain is too slow, then fluid- administration should be increased, and possible sources of ongoing fluid losses explored. Pulse, .respiration, and blood pressure measurements should be determined at hourly intervals. They are easily done and, particularly in the early stages of rehydration, give valuable information as to whether progress is being made. Initially, the pulse rate may be increased because of diminished circulatory volume, and its return to normal and stabilization are important to document. Respirations are often increased at first from metabolic acidosis, and the success of managing that problem will be reflected directly with the fall to normal of the respiratory rate. Blood pressure is particularly important in managing hypernatremic infants. If severe extracellular compromise is present at the beginning, blood pressure may be low and reflect frank shock; or there may be a slightly elevated pressure, reflecting a final homeostatic effort to preserve circulatory integrity. As with other vital signs, the normalization and stabilization of blood pressure represents an important measurement. Of further importance is the rise in blood pressure which occurs when fluid is being given too rapidly and when brain swelling is occurring. A rise in both systolic and diastolic blood pressure takes place over a relatively short time period and is one good parameter whereby seizures can be anticipated and avoided· by slowing fluid administration. Blood pressure should be measured every hour, and specific orders should be written so that the physician will be notified if an elevation occurs. State of consciousness and degree of irritability should be recorded with other measurements at hourly intervals. When present, the initial lethargy and irritability should disappear in the early hours of treatment. If and when irritability does reappear, it is likely to be in conjunction with rising blood pressure and heralds the impending onset of seizures. Other observations of the infant's condition should also be made systematically. The character of the skin is very important. Mottling and slow capillary filling are signs of peripheral vascular instability and they should rapidly be corrected. Similarly, tenting of the skin, if present, will diminish as the extracellular fluid compartment is expanded. If edema appears in the course of treatment, fluid administration is much too rapid and must be promptly readjusted. Once the infant is found to be hypernatremic, the planning of fluid administration requires only that readjustments in rate of administration be made according to the guidelines just discussed. As with any acutely dehydrated infant water is calculated to provide adequate maintenance and half replacement of acute losses during the first 24 hours. (The first 24 hour water calculation includes, of course, the volume of initial hydrating solutions.) Acute potassium losses have been found to be similar in all forms of gastroenteritis, and so maintenance and replacement potassium are also given according to the usual guidelines. Potassium is
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E.
HADDOW AND DANIEL
L.
COHEN
not begun until after the initial stage of hydration has been judged successful (i.e., shock corrected and urine output established) and should not exceed 40 mEq. per liter in an intravenous solution. Important restrictions exist in planning for sodium administration to hypernatremic infants, because it has been convincingly shown that the likelihood of developing cerebral edema and seizures increases steadily as the concentration of sodium falls progressively below 50 mEq. per liter in hydrating solutions. For this reason sodium concentration in the intravenous fluid must take precedence over the usual considerations of maintenance and replacement. It is recommended that all hydrating solutions employed in managing hypernatremically dehydrated patients contain between 50 mEq. and 75 mEq. of sodium per liter (after initial hydration with normal saline or Ringer's lactate). While it may appear inconsistent to give this much sodium to an individual whose serum sodium is already high, it is important to appreciate that in most instances total body sodium is still depleted. The major concern after extracellular compromise has been corrected is the prevention of seizures during the remainder of rehydration. The sodium concentration of the intravenous fluid is a major factor in preventing seizures. An additional electrolyte to be considered in the present problem is calcium. It is commonly observed that serum calcium concentrations are low either on admission or during the first day of therapy. On occasion, hypocalcemia persists and the patient becomes symptomatic on the fourth or fifth day of management. It is reasonable to add calcium to the fluid regimen, and 16 to 20 mg. of elemental calcium per kg. of body weight for young children may be added to each day's intravenous fluids with safety. A fluid regimen for such an infant would begin with an acute infusion of normal saline or Ringer's lactate over the first 2 hours. (A reasonable rate would be 20 ml. per kg. per hr.) During that time calculations would be made for the first 24 hours' fluid volume allotment. Then, following the initial infusion, the remainder of the day's fluid would be evenly spaced over the remainder of the 24 hours. That fluid would consist of sodium, 50 to 75 mEq. per liter; potassium, 30 to 40 mEq. per liter; and calcium, 5 to 10 mEq. per liter. During the second 24 hours, maintenance fluid volume would be combined with the remainder of replacement volume and the fluid composition would remain the same as the first day. Once the diagnosis ofhypernatremia has been established and appropriate fluids have been begun, then a chart can be made which contains the vital signs, weight, and other measurements to be used in following the infant's progress. With proper monitoring and interpretation of such recordings, a smooth recovery can be anticipated, and the serum sodium will gradually fall to normal over the first few days.
REFERENCES 1. Bruck, E., Abal, G., and Aceto, T., Jr.: Therapy of infants with hypertonic dehydration due to diarrhea. Amer. J. Dis. Child., 115:281-301, 1968.
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