fluidos y electrolitos- pediatrics
DESCRIPTION
Fluidos y Electrolitos- pediatricsTRANSCRIPT
ABBREVIATIONSADH: Antidiuretic hormone or
vasopressinECF: Extracellular fluidICF: Intracellular fluidRTA: Renal tubular acidosisDKA: Diabetic ketoacidosisDI: Diabetes insipidus
Pediatrics in Review Vol. 17 No. 11 November /996 395
BACK TO BASICSA review of
the scientific
foundations
of current
clinical practice
Fluids and Electrolytes-Clinical AspectsNicholas Jospe, MD* and Gilbert Forbes, MDI
Medical practice rests on the foundation of science. Clinicians are constantly making practical decisions and dealing
with immediate situations that demand solutions. Time should be taken to focus on those scientific principles that
underlie our diagnostic and therapuetic maneuvers. This section of Pediatrics in Review presents selected topics that
are relevant to practice from the areas of physiology, pharmacology, biochemistry, and other disciplines; clarification
of these will augment the pediatrician’s understanding of clinical procedures.
Changes in volume and composition
of body fluids due to disorders offluid and electrolyte balance causevarious common clinical illnesses.The rationale for reviewing the diag-nosis and management of fluid and
electrolyte disorders was eloquentlydenoted by Dr Altemeier, when hesuggested that this knowledge
belongs among the core conceptsneeded by the “keepers of the gates,”
that is, primary care pediatricians.’ Inthe body, homeostasis is maintainedby the coordinated action of behav-ioral, hormonal, renal, and vascular
adaptations to volume and osmoticchanges. These core issues have been
outlined in a previous article in thisjournal by Dr Hellerstein, and thecurrent article proceeds from that dis-
cussion.2 Following introductorycomments about body fluid volumeand composition, we provide an
overview of some of the etiologies ofthe disorders of volume, tonicity, andcomposition of body fluids and of thetherapy to correct these disorders.
�Associate Professor of Pediatrics.
‘Professor of Pediatrics, Division of Pediatric
Endocrinology, University of Rochester School
of Medicine and Dentist,y, Rochester, NY.
Sodium, Osmolality, and theVolume of Body Fluids
Total body water, which is 55% to72% of body mass, varies with sex,age, and fat content and is distributed
between the intracellular and extra-cellular spaces. The extracellularfluid (ECF), which comprises aboutone third of total body water,includes the intravascular plasmafluid and the extravascular interstitialfluid. Plasma ions include primarilyNa4, C1, and HCO3, which are
excluded from intracellular environ-ments, and lesser amounts of potassi-um (K�), magnesium, calcium, phos-phates, sulfates, organic acids, and
protein. Interstitial fluid, which sur-rounds the cells, has the same compo-sition as plasma, but with less pro-tein. The principal components ofintracellular fluid (ICF) are K�, pro-teins, magnesium, sulfates, and phos-phates.
In the ECF, Na� and C1 constitute90% or more of the effective solutes.Serum Na� concentration defines therelative amount of sodium and waterin plasma; the maintenance of a nor-mal Na� concentration, thus, con-
tributes to regulation of the volumeof body fluids. The size of the ECFand ICF compartments depends on
the amount of water within each; the
distribution of water depends on theirosmolality. The osmolality of a solu-
tion is a function of the number ofsolute particles or osmoles per unitvolume. In a given patient, the effec-
tive osmolality may be calculated asfollows, using the values of 2.8 and1 8 to convert values of blood ureanitrogen (BUN) and glucose, respec-lively, to mOsni/L:
Osmolality = 2 [Na� in mEq/Ll #{247}[BUN in
mg/dL]/2.8 + [Glucose in mg/dLJ/l8
Normal serum osmolality (265 to285 mOsm/L) is maintained by kid-
ney function, which dilutes or con-centrates urine. This is accomplishedby a variety of mechanisms involvingglomerular filtration, arterial pres-sure, blood flow, physical factors in
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TABLE!. Maintenance Requirements for Fluid and Electrolytes, Based on Body Weight
Body Weight 0 to 10 kg 10 to 20 kg >20 kg
Total Water 100 mL/kg 1000 mL +50 mL/kg for 1500 mL #{247}20mL/kg for
Volume each kg >10 kg each kg >20 kg
Sodium 3 mEq/kg 3 mEq/kg 3 mEq/kg
Potassium 2 mEq/kg 2 mEq/kg 2mEq/kg
Chloride 5 mEq/kg 5 mEq/kg 5 mEq/kg
396 Pediatrics in Review Vol. 17 No. /1 November /996
FLUIDS & ELECTROLYTESClInIcal Aspects
the kidneys, the sympathetic nervoussystem, and hormones such as aldos-
terone, atrial natriuretic factor, vaso-pressin, and dopamine. These sys-
tems converge to control water andelectrolyte balance through glomeru-lar ultrafiltration of the plasma fol-
lowed by changes in the electrolytecontent of this ultrafiltrate by tubularreabsorption and secretion. Thesemechanisms, together with thirst,
control both plasma osmolality and
plasma volume.
General Principles of theManagement of DehydrationDisorders affecting the composition
and volume of body fluids requireintervention to maintain or restorenormality. This intervention is
accomplished by: 1) supplying main-tenance requirements, 2) correctingvolume and electrolyte deficits, and
3) replenishing ongoing abnormallosses. The following guidelinesreview how to calculate maintenance
requirements, deficit replacement,
and provisions for ongoing abnormal
losses.
REQUIREMENTS FORMAINTENANCE FLUID ANDELECTROLYTES
As noted previously, homeostasis ismaintained by the coordinated action
of behavioral, hormonal, renal, andvascular adaptations. Outside of these
adaptations, the role of fluid and elec-
trolyte maintenance as a concept is tohelp the physician ensure preserva-tion of this homeostasis by providingall fluid and electrolyte needs whenthese cannot be met by the patient.
Maintenance requirements from sen-
sible and insensible fluid losses are to
be rigorous and depend on energy
expenditure, but they can be calculat-
ed adequately by using body weight.Insensible water losses through the
skin and the respiratory tract, whichusually are electrolyte-free, are high-
er in newborn infants than in adoles-cents. Sensible losses, primarily uri-nary, account for approximately 50%
of daily fluid requirements. Thus, uri-nary fluid losses need not be replacedas long as the total daily urine output
is not more than 50% to 60% of thecalculated water maintenance.
Caloric requirements for growth canbe estimated as equivalent on a kcal-for-mL basis to water requirements.
Factors that increase the requirementsfor calories and for water are fever( 10% for each degree C), physical
activity, ongoing gastrointestinal loss-es, hyperventilation, or hypermeta-
bolic states. Other conditions, such asanuria, oliguria, or congestive heartfailure, may reduce the requirements
for water. Maintenance requirementsfor water vary with weight and can becalculated as outlined in Table 1.Electrolyte requirements, which arerelatively constant throughout child-hood, also are outlined in Table 1. All
abnormal losses, such as those arisingfrom a stoma, nasogastric aspiration,
prolonged diarrhea, or burns, shouldbe analyzed, measured, and replacedvolume for volume.
ESTIMATION OF DEFICIT
Water and electrolyte deficits resultfrom either normal or increased lossesin the face of decreased or normalintake. Findings on history, physicalexamination, and laboratory studiesprovide the tools to gauge volumedepletion. One must inquire aboutfever, vomiting and/or diarrhea, andurine output to establish the site(s) of
fluid loss and the type and amount of
loss. Careful attention should be paidto recent feeding, including type andvolume of food and drink, and to
assessing weight change. The physicalexamination provides clues for esti-mating the extent of dehydration, asoutlined in Table 2. This informationis used to gauge the percent dehydra-
tion, which then is expressed as milli-liters of body water deficit per kilo-gram of body weight. For example, adehydration of 10% corresponds to awater deficit of 100 mL/kg bodyweight.
Measurement of electrolytes is notrequired if the patient appears to have
lost less than 5% of body weight andhas an obvious cause for the fluid loss.When the body weight loss is greater
than 5% or when the cause of thedehydration is uncertain, laboratory
studies should be obtained to look forabnormalities of electrolyte and acid-base balance. Laboratory findings mayinclude, in addition to serum elec-
trolyte abnormalities, elevations ofBUN, hematocrit, or albumin due tohemoconcentration. The plasma creati-nine concentration is a more reliableindex of renal function than is theBUN concentration because creatinineconcentration is influenced less by
dietary protein load and tissue break-down, although it does vary with ageand muscle mass. Most children do
not require pH, calcium, phosphorus,magnesium, glucose, or albumin con-centration determinations.
Isonatremic DehydrationThe most common cause of dehydra-tion in infants is diarrhea, which is anet fluid secretion greater than thecapacity of the intestine to absorbfluid, or failure to absorb normalsecretions. The fluid content of the
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- FLUIDS & ELECTROLYTESClinical Aspects
TABLE 2. Estimation of Dehydration
Extent of Dehydration Mild Moderate Severe
Weight Loss-Infants 5% 10% 15%
Weight Loss-Children 3%-4% 6%-8% 10%
Pulse Normal Slightly increased Very increased
Blood Pressure Normal Normal to orthostatic, Orthostatic to shock
>l0mmHgchange
Behavior Normal Irritable, more thirsty Hyperirritable to lethargic
Thirst Slight Moderate Intense
Mucous Membranes* Normal Dry Parched
Tears Present Decreased Absent, sunken eyes
Anterior Fontanelle Normal Normal to sunken Sunken
External Jugular Vein Visible when Not visible except Not visible even withsupine with supraclavicular supraclavicular pressure
pressure
Skin* (Less Useful in Capillary refill Slowed capillary Very delayed capillaryChildren >2 Y) >2 sec refill, 2-4 sec refill (>4 sec) and
(decreased turgor) tenting; skin cool,acrocyanotic, or mottled*
Urine Specific Gravity (SG) >1.020 >1.020; oliguria Oliguna or anuria
* These signs are less prominent in patients who have hypernatremia.
Pediatrics in Review Vol. 17 No. 11 November 1996 397
intestinal tract is a mixture of diet and
secretions from the stomach, the pan-creas, the bile ducts, and the intestine.The secretory process of diarrhea
causes Na�, Cl, and water losses. Indiarrhea from rotavirus infection, lossof HCO3 and K� in the small intes-tine leads to metabolic acidosis and
K� depletion. In general, childrenwho have a brief illness and anorexiapresent with proportional water and
electrolyte losses, that is, isotonicdehydration. Dehydration compro-mises the function of many organsystems so that body fluid homeosta-sis cannot be maintained. An impor-
tant treatment objective is to restorerenal function so that the kidney canassist in correcting the acid-base and
electrolyte imbalance. Moderate vol-ume depletion may be treated withoral fluids, even though parenteralfluid administration is the norm inNorth America and western Europe.
Indeed, rehydration therapy usingoral fluids is effective, cost-efficient,and adaptable and lowers hospital uti-lization. Parenteral fluids should begiven to children who have severevolume depletion, with altered states
of consciousness, intractable vomit-ing, and abdominal distention or
ileus. For infants weighing less than4.5 kg or who are younger than3 months, it is more prudent to pro-vide parenteral than oral therapy. The
following sections address parenteral
and oral rehydration, but monitoringof the patient’s status using clinicaland laboratory data is crucial toensure the proper implementation ofeither form of rehydration.
PARENTERAL REHYDRATION
The first phase of treatment is to
expand the vascular volume rapidly,with the goals of preventing shock
when a circulatory deficit is severeand improving renal function.Intravenous normal saline or Ringerlactate (10 to 20 mL/kg) should begiven over 1 hour. This infusionshould be subtracted from the pro-
posed total volume for the day. Fivepercent albumin, 10 mLlkg, is needed
only in neonates, malnourishedinfants, and hypernatremic patients inshock. The benefit of normal saline or
Ringer lactate is a transient expansionof the intravascular space, but thisbenefit dissipates as the crystalloid
solution equilibrates with the remain-der of the extravascular interstitial
fluid. Compared with normal saline,Ringer lactate has a more physiologicNa� to Cl ratio (1.17:1); has a slight-ly lower Na concentration ( I 30 mEq/L); and contains calcium, potassium,and lactate.
The next phase of treatment isaimed at correcting the deficit, pro-viding maintenance, and, if needed,replacing ongoing abnormal losses.In severe depletion, it may be appro-
priate to give one half of the calculat-ed deficit over the first 8 hours and
the second half over the next16 hours; maintenance needs are pro-vided at a steady rate. During this
phase, 5% glucose should be used asthe stock solution; NaCI is added
according to the estimated need.Children who have isonatremic dehy-dration require 8 to 10 mEq of Na�per kg of body weight for repletion of
deficit and 3 mEq/kg per day formaintenance. This Na� is given in avolume consisting of the calculatedmaintenance for water (Table I) andthe estimated water deficit (Table 2).
Once urine flow is verified, KC1 isadded at a concentration of 20 mmol/L to prevent the clinical effects of K’�
depletion. Intravenous K� administra-tion should not be greater than
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398 Pediatrics in Review Vol. 17 No. 11 November 1996
FLUIDS & ELECTROLYTESClinical Aspects
4 mEqlkg per day to avoid exceeding
the capacity for cellular uptake of K�,
thereby inducing hyperkalemia. Inmost infants who have diarrheal dehy-dration, diarrhea subsides rapidly withtherapy, presumably from “bowel
rest.” However, for patients who havecontinued heavy diarrhea, stool vol-umes should be measured to maintainan appropriate intake relative to out-put; such losses should be replaced
volume for volume. Normal saline ortwo-thirds normal saline with 20mmolIL of KC1 may be used safely toreplace most fluid losses from gastricor intestinal drainage. Metabolic aci-
dosis may occur from diarrhea, but itis usually mild and resolves oncerenal function is restored. In severe
metabolic acidosis, bicarbonateadministration may be required.
ORAL REHYDRATION
As noted previously, therapy usingoral fluids is effective, even withongoing diarrhea or vomiting. For themajority of patients who have gastro-enteritis and either no dehydration or,
at most, moderate dehydration, oralrehydration therapy is all that is nec-essary. This distinction is importantbecause there are two categories oforal hydration solutions available. Thefirst includes the oral maintenancesolutions used either after parenteralrehydration or early in diarrheal ill-
ness to prevent dehydration. These are
used to replace losses in infants whohave gastroenteritis from commoninfections. The second categoryincludes the oral rehydration solu-
tions, which have a higher Na� con-
centration. As a guideline for oralrehydration, small aliquots are given
as tolerated to provide approximately50 mL/kg over 4 hours in mild dehy-dration and up to 100 mL/kg over6 hours in moderate dehydration.Once rehydration is accomplished,maintenance fluid is given at100 mLlkg per day. The electrolyte
composition (in mEqfL) and carbohy-
drate composition (in percent) of thecommercially available oral solutionsare indicated in Table 3. Of note,
household clear-liquid beverages,
such as broths, juices, sodas, and tea,are inappropriate for the treatment ofdiarrheal dehydration.
Hyponatremia andHyponatremic Dehydration
The differential diagnosis of hypona-tremia will be reviewed in the context
of hypovolemia, euvolemia, andhypervolemia to underscore the fact
that a low serum Na� concentrationdoes not necessarily imply decreasedtotal body Na’ content. The signs andsymptoms of hyponatremia correlatewith the rapidity and extent of the fallin serum Na� concentration. Centralnervous system (CNS) symptoms
include apathy, nausea and vomiting,headache, seizures, or coma; the mus-culoskeletal symptoms include
cramps and weakness. Thus, infantswho have hyponatremic dehydration
may appear quite ill, because fluidloss in combination with hyponatrem-ia leading to circulatory insufficiency
causes a disproportionate reduction inECF volume. As serum osmolalityfalls, water moves into cells, causingmusculoskeletal dysfunction andputting the brain at risk for swelling.The brain adapts to hyponatremia bypushing interstitial fluid into the cere-brospinal fluid and by extruding cellu-
lar solutes, primarily K� and aminoacids. The relevance of this point is tostress that rehydration puts the brainat risk for dehydration, or even injury,
if the correction of fluid and elec-
trolyte losses is much more rapid thanthe rate at which the brain can recoversolute. In severe hyponatremia, it is
advisable to effect a correction inplasma Na’� concentration of no more
than 10 to 12 mEq/L per day to avoidundue fluid shifts.
DIFFERENTIAL DIAGNOSIS
Hypovolemia
In pediatrics, by far the most frequent
cause of hypovolemic hyponatremiais viral gastroenteritis, with vomiting,
diarrhea, or both. Other causes ofhypovolemic hyponatremia include
TABLE 3. Composition of Commercial Oral Hydration Solutions
Na’ (mEqlL) K’ (mEqIL) cr (mEq/L) BASE (mEqlL) CARBOHYDRATE(% WEIGHT FORVOLUME)
MAINTENANCESOLUTIONS:
Resol (Wyeth)* 50 20 50 Citrate, 34 2% Glucose
Ricelyte (Mead Johnson) 50 25 45 Citrate, 34 3% Rice syrup solids
Pedialyte (Ross) 45 20 35 Citrate, 30 2.5% Glucose
REHYDRATION
SOLUTIONS:
Rehydralite (Ross) 75 20 65 Citrate, 30 2.5% Glucose
World Health Organization
formulation(for use in cholera)
90 20 80 HCO#{231},30 2% Glucose
* Includes cakium, 4 mEqIL; magnesium, 4 mEqIL; phosphate,5 mEqIL
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Pediatrics in Review Vol. /7 No. /1 November /996 399
FLUIDS & ELECTROLYTESClinical Aspects
percutaneous losses or third space
sequestration of fluid, as in ascites,burns, or peritonitis. Patients whohave cystic fibrosis are prone to
develop hyponatremic dehydration,
particularly in hot weather, becausetheir sweat has an abnormally high
concentration of Na� and Cl. In all ofthese cases, urinary Na� concentration
is expected to be <20 mEq/L as thebody seeks to conserve Nat On the
other hand, renal loss (urinary Na�>20 mEqfL) also can cause hypov-
olemic hyponatremia. This may fol-low the use of diuretic medications oroccur in salt-wasting nephropathy,proximal renal tubular acidosis
(RTA), and lack of or resistance to
mineralocorticoid.
Euvolemia
The most common cause of eu-volemic hyponatremia is the syn-
drome of inappropriate antidiuretichormone (ADH) secretion, which is a
problem of water retention, not Na�depletion (urinary Na� usually>20 mEqIL). The causes of inappro-priate ADH secretion include tumors,pulmonary disorders, CNS infection,and a host of drugs. In addition,euvolemic hyponatremia may occur ininfants fed excessively diluted infant
formula.
Hypervolemia
Hypervolemic hyponatremia may
result from conditions associated with
edema in which water is retained in
excess Na�, such as nephrosis, con-gestive heart failure, cirrhosis, orrenal failure.
MANAGEMENT
The general principles for managing
dehydration have been outlined previ-ously, and additional guidelines areincluded in this section.
Hypovolemic patients who havehyponatremia require volume expan-sion, using a solution containing saltto correct the Na� deficit (10 to12 mEqlkg of body weight or even
15 mEq/kg in severe hyponatremia)and to include the Na� maintenanceneeds (3 mEq/kg per day in 5% dex-trose solution). For a serum Na� con-centration of 120 to 130 mEq/L, thisamount should be given over a24-hour period. For a serum Na� con-
centration <120 mEqIL, the rehydra-
tion should be spread out over thenumber of days it takes to raise theNa� concentration to 130 mEq/L by
10 mEq/day (eg, 2 days for a Na� of1 10 mEq/L) and provide that fractionof the deficit along with the daily
maintenance requirement. On theother hand, symptomatic hyponatrem-
Ia (headache, lethargy, disorientation)requires urgent therapy to prevent the
potential complications of hypona-tremia, such as seizure or coma,which result from the movement ofwater into brain cells. In the presence
of these symptoms or complications,Na’� administration is urgent, regard-
less of the absolute level of serumNa’�. Hypertonic saline (3% salinesolution), either with or without loop
diuretic agents and water restriction,should be used to raise the serum Na�by I to 2 mEqfL per hour or halfwaytoward normal during the first 8
hours. A correction using 3% salineover 4 hours can be calculated accord-ing to the following formula:
Sodium deficit in mEq = (125 - observed[Na�]) X body weight in kg x 0.6
Finally, the presence of high urinaryNa� and low urinary K� excretion,when these reflect the kidney’s lack ofmineralocorticoid action, indicates the
need for mineralocorticoid medicationin addition to fluids to ensure correc-
tion of the volume deficit.
Euvolemic patients who have
hyponatremia require restriction ofwater intake. Asymptomatic individu-als require only water restriction; ede-
matous patients require restriction ofboth water and Na� (greater restric-tion of water than of Nat), using
diuresis with intravenous furosemide.Na� administration in this setting is
inappropriate.
Hypervolemic patients who havehyponatremia require water and sodi-
um restriction. The hypervolemicstate may be accompanied by edemaand cardiopulmonary evidence of
fluid overload and implies retention of
water and Na4 with an inappropriatelyhigh proportion of water relative to
Na4. In patients whose renal failure ismild, water restriction is effective, butdialysis is required in those who haveoliguria or anuria.
Hypernatremia andHypernatremic Dehydration
As a rule, the hypernatremic patient
also is dehydrated, with a greater lossof water relative to solute; eventhough total body Na4 may be
increased or normal, it most com-monly is decreased. Thus, as in
hyponatremia, the serum Na4 concen-tration does not reflect the total bodyNa4 content. As hypernatremia leads
to hypertonicity of the plasma, thebody protects itself by secreting ADH
and by increasing thirst. Thus, mdi-viduals who are unable to secrete orrespond to ADH and those who have
no access to water are particularlyprone to hypernatremia. Affected
patients, especially infants, frequentlyexhibit disturbances of conscious-ness, such as lethargy or confusion,
and other signs of neuromuscular irri-tability, such as muscle twitching,hyperreflexia, or even convulsions.Finally, fever is not uncommon, andthe skin may feel thickened ordoughy or velvet-soft in texture.
Extracellular hypertonicity drawswater from cells, thus decreasing cell
size. In the brain, this may lead to
tearing of arachnoid tissue and tosubarachnoid, intradural, or subduralhemorrhages. When the hypertonicity
develops insidiously, brain cells adapt
by generating intracellular osmoles, aprocess called “idiogenic osmole pro-
duction.” This process decreases theextracellular-to-intracellular osmoticgradient, thereby protecting against
cell shrinkage. To avoid inducingcerebral edema once correction ofplasma hypertonicity is initiated, it is
important to know that dissipation ofthe intracellular osmoles is not rapid.Hence, correction of the hyperna-
tremia should be relatively slow.Severe hypernatremia (serum Na4
concentration >160 mEqfL) can resultin permanent CNS sequelae and isassociated with a mortality that
reaches 10%.
DIFFERENTIAL DIAGNOSIS
Diarrhea, which usually results inisonatremic or hyponatremic dehy-
dration, may cause hypernatremia inthe presence of persistent fever,anorexia, vomiting, and decreasedfluid intake. Beyond gastrointestinaldisease, other causes of hyperna-
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tremia include water and Na4 deficit
FLUIDS & ELECTROLYTESClinical Aspects
400 Pediatrics in Review Vol. 17 No. 11 November 1996
from percutaneous losses or renallosses and water losses from central
or nephrogenic diabetes insipidus(DI) or pharmacologic agents, such as
lithium, cyclophosphamide, or cis-platin. These entities are characterizedby a relatively greater water than Na�
loss and usually induce a hypo-volemic state. Na� excess from saltpoisoning causes hypernatremia butnot dehydration. Finally, prematurity,
inability to regulate water intake, lackof renal regulation, hyperpnea,
diaphoresis, high solute intake, andenteric infection with organisms caus-ing inflammation and malabsorptioncan cause hypernatemia. The modern
tendency is to offer milk (cow or soy)or infant formula feedings to infantswho have diarrhea as a means ofimproving nutrition. Such feedings
should have a low content of proteinand electrolytes that require renalexcretion. Half-strength formula orhuman milk are obvious choices.
MANAGEMENT
Hypovolemic patients who have
hypernatremia have a relativelygreater water than Na� loss. Initial
therapy requires administration of nor-mal saline or Ringer lactate to restorean effective circulating plasma vol-ume. Five percent albumin solution orplasma also can be used. Hypovolemic
patients who have hypernatremiarequire a hypotonic solution contain-ing salt to restore the Na4 deficit (2 to5 mEqlkg of body weight) and tobegin the Na4 maintenance (3 mEq/kgof Na4) in solution containing 20 to40 mmollL of KC1 and 5% glucose.For a serum Na� concentration of 150to 160 mEq/L, this volume should begiven over a 24-hour period. Because
ECF osmolarity may fall more rapidly
than the brain can dissipate the idio-genic osmoles generated to protectintracellular osmolarity, an elevated
serum Na� concentration should becorrected by no more than 10 mEq/Lper day. For a serum Na4 concentra-
tion >160 mEq/L, the rehydration
should be spread out over the numberof days necessary to lower the Na4
concentration to 150 mEq/L by10 mEq/day (eg, 2 days for a Na4 of170 mEq/L). Both the daily fraction ofthe deficit and the daily maintenance
requirement should be provided. The
degree of hypotonicity of the fluidadministered is less important than tothe rate of correction.
Euvolemic patients who havehypernatremia resulting from excessinsensible water losses or from DI(solute-free water losses) requirewater replacement and, where appro-
priate, therapy for the management ofthe DI. Rehydration should be
accomplished by using hypotonicsaline, aiming to correct the serumNa4 concentration by no more than
10 mEq/L/day. The “water deficit” inDI, assuming that total body Na4 hasremained unchanged, may be estimat-
ed by using the following formula
(adapted from Avner3):
Water deficit = (normal body
water) - (current body water)
Current body water = 0.6 x body
weight in kg x normal [Na� 1/
observed [Na�]
Normal body water = 0.6 x body
weight in kg
Hypervolemic patients who have
hypernatremia resulting from excesssalt administration or hyperaldostero-nism require diuresis with concomi-
tant water administration.
PotassiumPotassium is the most abundant intra-
cellular cation; thus, acute serumchanges do not reflect total body K4stores. Chronic changes, especially in
hypokalemia, do reflect body stores.The serum K4 concentration is adjust-ed in the terminal nephron of the kid-ney, and a small loss occurs throughthe stool. The ratio of intracellular toextracellular K4 is the major determi-nant of the resting electrical potential
across cell membranes and, thus, con-tributes to the action potential ofneural and muscular tissue. Abnor-malities of serum K4 are potentiallylife-threatening, due to effects on car-diac function, because of the role of
K4 in neuromuscular irritability. Also,K4 plays an important role in cellmetabolism. In acidemia, the concen-tration of K4 in the ECF is increasedby cellular secretion of K4; the con-centration of serum K4 usually rises
by approximately 1 mEq/L when the
pH drops by 0.1 unit; in alkalosis, theconverse occurs.
Hypokalemia
DIAGNOSIS
Hypokalemia (serum K4 concentra-
tion <3 mEqfL) has a lengthy differ-ential diagnosis. The most frequentcauses of net loss of K4 are gastroin-
testinal losses or renal losses. Giventhat the K4 concentration of gastricfluids is fairly high, nasogastric suc-tion or protracted vomiting may
induce hypokalemia. Renal losses canresult from either administration ofdiuretics or mineralocorticoids orfrom intrinsic renal tubular disease,
such as Bartter syndrome. Barttersyndrome is characterized by hyper-reninemia and hyperaldosteronism,which results in hypokalemia,
hypochloremia, and alkalosis.
Because nearly all K4 is intracellular,hypokalemia also may result fromtranscellular shifts of K� from serumto cells, as in acute alkalosis. Themost severe manifestations ofhypokalemia are arrhythmias, neuro-
muscular excitability (hyporeflexia orparalysis, decreased peristalsis orileus), and rhabdomyolosis. A goodestimate of intracellular K4 can bemade from the electrocardiogram,where flattened T waves, a shortened
P-R interval and QRS complex, and
finally, the appearance of U waves
are observed.
MANAGEMENT
In the presence of cardiac arrhyth-mias, extreme muscle weakness, orrespiratory distress, patients shouldreceive KCI intravenously and closecardiac monitoring. Once the serumK4 is stabilized, the oral route ofadministration is preferable. Thechoice of potassium salt depends onthe etiology. If the patient is likely tobe hypophosphatemic, a phosphatesalt should be used. In metabolic
alkalosis, KC1 should be used; inrenal tubular acidosis (RTA), eitherthe citrate or bicarbonate salt should
be used. When hypokalemia is associ-ated with depleted body stores orchronic K4 wasting states, K4 supple-mentation may be needed for weeks
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FLUIDS & ELECTROLYTESClinical Aspects
even pulmonary edema.
Pediatrics in Review Vol. /7 No. /1 November /996 401
at doses of 3 to 5 mEq/kg per day.
Therapy for Bartter syndromeincludes prostaglandin synthetase
inhibitors, KC1, and a potassium-
sparing diuretic.
Hyperkalemia
DIFFERENTIAL DIAGNOSIS
The most common cause of hyper-
kalemia (serum K4 concentration>5.5 mEq/L) in infants and children
is “pseudohyperkalemia” from
hemolysis of the blood sample, which
warrants repeating the determination
in a free-flowing venous samplewhen this is suspected. Children may
display hyperkalemia in disordersresulting from or accompanied by
transcellular shifts, as occur in meta-bolic acidosis or tissue catabolism, or
in disorders of decreased urinary
excretion, such as acute or chronic
renal failure, volume depletion, orhypoaldosteronism. In salt-losing
congenital adrenal hyperplasia due to
complete deficiency of the enzyme21-hydroxylase, the symptoms in
affected male infants appear in thefirst weeks of life and include dehy-dration and failure to thrive togetherwith low serum Na4 and high K4 con-
centrations. Affected female infants
usually are diagnosed at birth beforeelectrolyte abnormalities develop
because of ambiguity of the externalgenitalia. Finally, certain diuretic
medications, such as angiotensin-
converting enzyme inhibitors and
non-steroidal anti-inflammatory
agents may induce hyperkalemia.
DIAGNOSIS
Manifestations of hyperkalemia
include cardiac arrhythmias, pares-thesias, muscle weakness, or paraly-
sis. As with hypokalemia, the electro-cardiogram is helpful in diagnosis;narrow, peaked T waves and short-
ened QT intervals are observed at K4concentrations >6 mEq/L and
depressed ST segment and widenedQRS complex at K4 concentrations
>8 mEq/L.
MANAGEMENT
Patients should have close cardiac
monitoring. The fastest way to antag-
onize potentially life-threateninghyperkalemia is to administer intra-
venous calcium. The onset of actionis rapid and the duration is less than
30 minutes. Emergent measures tocause K4 to redistribute to the intra-
cellular space include the administra-tion of NaHCO3 or glucose andinsulin. Thereafter, ion exchange
resins, such as sodium polystyrene
sulfonate (Kayexalate#{174}), are used
either orally or as a retention enema.
Finally, severe hyperkalemia may betreated with hemodialysis, which is the
most effective way to remove K4,yielding quicker results than peritonealdialysis.
Acid-Base DisordersThe pH of the body fluids normally is
between 7.35 and 7.45. When the pH is
brought outside this range by a primary
disturbance, it is restored toward nor-mal by one of the two major homeosta-
tic mechanisms that buffer pH changes.
These two buffering mechanisms usethe lung and the kidney, which modify
the ratio of the partial pressure of CO2(Pco2) to the concentration of HCO3.In plasma, the carbonic acid-bicarbon-
ate system governs both Pco2 and
HCO3:
H20 + C0244 H,C03 +-* H� + HC03
This relationship is described by the
Henderson-Hasselback equation:
pH = 6. 1 4 log [HCO3i/[H2C03]
where 6.1 is the negative logarithm of
the dissociation constant of carbonic
acid; the concentration of H2C03 fre-quently is expressed as the partial pres-
sure of CO2 (normal, 35 to 45 mm Hg).Acid-base homeostasis uses buffers
that absorb excess H� ions. The firstmechanism by which the pH is main-tained includes both extracellular
buffers, such as the bicarbonate/carbon-ic acid system and the serum proteins,
and intracellular buffers, such as pro-teins, phosphates, and hemoglobin. The
second mechanism for maintaining pHis alveolar regulation of the Pco2.Having a normal Pco2 or a normal con-
centration of HCO3 does not imply a
normal pH; thus, to evaluate acid-base
disorders, a concomitant arterial (orvenous) blood gas and electrolyte
chemistry panel are required. It isimportant to remember that infants nor-mally maintain a slightly lower HCO1concentration (21 .5 to 23.5 mEq/L)than adults (23 to 25 mEqfL). Acid-base disturbances can result from alter-
ations in either Pco2 or HCO3 due tochanges in acid production, acid buffer-
ing, and acid excretion. A deviation inHCO3 causes a metabolic alkalosis oracidosis; a deviation in Pco, causes a
respiratory alkalosis or acidosis.
Metabolic AcidosisAcidosis results from the addition ofacid or the removal of alkali frombody fluids, and it evokes a compen-
satory response consisting of in-creased alveolar ventilation (respira-tory alkalosis) and a fall in Pco2. Thisadaptation, hyperpnea (defined as
deep, pauseless respirations), doesnot lead to complete normalization ofpH, but it occurs rapidly, beginningwithin minutes. The clinical manifes-
tations of acidosis include depressedmyocardial contractility, arrhythmias,
arteriolar dilatation, hypotension, and
DIAGNOSIS
A fixed acid (HA) added to the extra-cellular fluid will be buffered in large
part by HCO3:
HA + NaHCO3 �-* NaA + H,CO3#�H,O + CO2
The formation of the sodium salt
implies loss of HCO3 and formationof anions unmeasured in the routinelaboratory determination that include
proteins, phosphates, sulfates, and
organic anions. These unmeasuredanions are referred to as the anion
gap, which can be estimated indirect-
ly as:
Anion gap = Na� - (C� + HC01)
= lO-l2mEq/L
The anion gap is kept steady by renalexcretion of the constantly producedunmeasured anions, but this steadystate is disturbed if large amounts ofacid are added exogenously or pro-duced endogenously. Thus, for everymole of titratable acid, the concentra-
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402 Pediatrics in Review Vol. 17 No. 1/ November /9%
FLUIDS & ELECTROLYTESClinical Aspects
tion of HCO3 falls by 1 mole. Theanion gap can be either increased or
normal in acidosis. Acidoses with a
normal anion gap (hyperchloremia)result from either renal or gastroin-testinal loss of HC03. The acidoseswith an increased anion gap include
diabetic ketoacidosis (DKA), lactic
acidosis, toxin ingestions (salicylates,
ethylene glycol), and uremia. Of note,
a decreased anion gap may occurwithout the presence of acidosis inconditions accompanied by hypoalbu-minemia, hyperkalemia, hypercal-
cemia, or laboratory errors.
DIFFERENTIAL DIAGNOSISNormal Anion Gap (Hyperchloremic)Acidosis
When HC03 is lost from the body,
either through the gastrointestinaltract or the kidney, Cl is the only
other anion readily available to helpmaintain fluid volume. Dispropor-
tionately increased Cl absorption,along with Na4, compensates for theloss of HCO3, causing hyper-
chloremia and leaving the anion gapunchanged. Diarrheal fluid, which in
infants and children commonly is
high in HC03, is high in K4 and lowin Cl. In addition, ECF contraction
from diarrhea results in hyper-
chloremia because the remaining C1is confined to a smaller volume of
distribution. Thus, diarrhea causeshypokalemia and hyperchloremicacidosis. Failure to excrete acid
occurs in mild chronic renal insuffi-ciency and RTA. RTA is a group oftubular transport disorders thatincludes three primary types summa-
rized below.
In type I or distal RTA, which is
caused by impaired distal H4 secre-tion, urine pH is greater than 6. The
defective H4 secretion causes renalHCO3 wasting, especially during
periods of rapid growth when largeamounts of HCO3 are required tobuffer endogenously generated acid.
In type 2 or proximal RTA, urinepH also is greater than 6 because
there is a failure to reabsorb HC03.K4 loss also is common, leading tohypokalemia. Type 2 RTA may be an
isolated finding but more frequentlyoccurs as part of the Fanconi syn-
drome, which also includes urinaryproximal tubule loss of glucose, cal-cium, phosphate, amino acids, sodi-
um, potassium, uric acid, and otherorganic acids. Failure to thrive is aprominent clinical feature of type 2RTA.
Type 4 RTA in pediatrics com-
monly results from a variety of con-ditions with a lack of or resistance toaldosterone causing impaired K4 and
H4 secretion. Findings includeincreased plasma renin activity,hyponatremia and hyperkalemia, andvolume depletion.
Increased Anion Gap Acidosis
Common causes include DKA, lacticacidosis, ingestion of toxins, and
renal failure. In DKA, the overpro-duction and underutilization of beta-hydroxybutyric acid and acetoaceticacid cause a metabolic acidosis,
which is characterized by a low plas-ma HCO3 concentration andincreased concentration of the anions
of these acids. Lactic acidosis mayoccur in the setting of sepsis andhypovolemic or hypotensive shock.In addition, lactic acidosis may result
from certain inborn errors of carbo-
hydrate or amino acid metabolism.Within the category of toxin inges-
tion in children, salicylate overdoseis not infrequent. The initial responseis a respiratory alkalosis followed by
ketosis, lactic acidosis, and loss of
HCO3, which is used to buffer thesalicylic acid. Vomiting may compli-cate the situation further. Younger
children more likely will presentwith metabolic acidosis than respira-
tory alkalosis. Ethylene glycol inges-tion (found in antifreeze or cleaning
solutions) may be dangerous or fatal.In acute or severe chronic renal fail-
ure, metabolic acidosis is commonbecause anions such as phosphate
and sulfate are not excreted, con-tributing to the unmeasured anionconcentration.
TREATMENT
Sodium bicarbonate is the agent of
choice in acute acidosis requiringintervention. No matter what the
cause, bicarbonate should be givenwhen plasma HCO3 is <5 mmol/L.
Bicarbonate should be added to a
hypotonic solution and given as acontinuous infusion over 1 hour. Theamount to infuse may be calculatedby using the following formula:
Amount to infuse in mEq = body weight
in kg (15 - observed [HCO31) x 0.5
In diarrhea, the severity of the aci-dosis varies according to the etiology.
With severe watery diarrhea, the stoolHC03 concentration may reach40 mEq/L, resulting in moderate-to-
severe metabolic acidosis. In additionto volume replacement, which is theprincipal arm of therapy, it may be
necessary to add HC03 to the intra-
venous fluid. Before giving HCO3,
the serum K4 concentration must bedetermined. If it is normal or low,
treatment with HCO3 may induce orworsen hypokalemia and lead to neu-
romuscular complications. It shouldbe emphasized, however, that forpatients who have moderate-to-mildacidosis (HC03 >10 to 15 mEq/L or
pH >7.2), all that is required is to cor-rect the dehydration and electrolyte
losses so the kidney can excrete theexcess H4 ions effectively.
Children who have type 1 RTAneed 5 to 15 mEqfkg per day of sup-plemental alkali. Oral sodium citrateis more palatable than bicarbonatesalt. The maintenance dose is highly
variable and is titrated to normalize
the patient’s plasma HC03 concen-tration. A fixed HC03 loss persists,
even when the serum HC03 concen-
tration is low, so these infants are atrisk for severe acidosis when they
cannot maintain oral alkali supple-mentation. After age 6 years, affected
children exhibit a reduction in urinaryHC03 loss, allowing a reduction inthe dose of alkali. Prior to appropriate
treatment, renal K4 and Ca4 lossesmay occur. Children who have type 2
RTA may require up to 20 mEqlkg ofsupplemental alkali as well as oral
potassium supplements. Childrenwho have type 4 RTA require admin-istration of NaCI and possibly miner-
alocorticoid replacement. Hyperkale-mia responds to restriction of oralintake of K4; low doses (I to 2 mEq/kg per day) of HCO3 may berequired for correction of acidosis.
In DKA, therapy with fluids andinsulin allows for the ketoacids to bemetabolized and for acid to be excret-
ed by the kidneys, thus regeneratingHCO3. Therefore, administration of
bicarbonate is not required for mostpatients who have DKA. Moreover,the potential complications of bicar-bonate therapy include rebound
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Pediatrics in Review Vol. 17 No. 11 November 1996 403
hypokalemia, “overshoot” metabolic
alkalosis, hypernatremia, and para-doxic CNS acidosis. However, manyrecommend administering bicarbonate
if the pH is below 7.0.In severe lactic acidosis, the main-
stay of treatment is correction of theunderlying process. However, admin-istration of bicarbonate offsets thenegative inotropic and arrhythmo-
genic effects of acidemia and offers
time to address the principal cause.For patients who have ingested ethyl-ene glycol, therapy includes gastriclavage, charcoal administration, andintravenous ethanol or even immedi-ate dialysis in severe cases.
Metabolic AlkalosisAlkalosis results from a gain of base
or a loss of acid. It leads to tissuehypoxia, CNS changes, and muscularirritability and may cause seizuresand arrhythmias. The common clini-cal manifestations, thus, are lethargy,confusion, and ultimately, neuromus-cular irritability and seizures. Somepatients exhibit diminished respira-tory excursion as the body attempts to
retain CO2.
DIFFERENTIAL DIAGNOSIS
The causes of metabolic alkalosis fall
into four categories. The first catego-ry includes alkalosis due to alkaliadministration. The second comprisesthe chloride-responsive alkaloses,usually from gastrointestinal acid and
chloride loss; this category includesthe most common cause of hypo-
kalemia in pediatrics, namely, vomit-
ing and/or nasogastric aspiration. Inthese patients, urinary Cl concentra-tion usually is below 20 mEqfL. Thethird group includes chloride-resis-tant alkaloses, such as Cushing syn-
drome, Bartter syndrome, or primaryaldosteronism. The last categoryincludes secondary aldosteronism orother causes of mineralocorticoid
excess and, finally, refeeding follow-ing fasting and in persons who haveanorexia nervosa or bulimia.
TREATMENT
Therapy is centered on identifyingand treating the underlying pathology.In mild-to-moderate alkalosis, provi-sion of Cr will allow the kidney to
excrete the excess base. In severe
alkalosis, hydrochloric acid adminis-tration may be necessary. Alternative
choices for therapy are ammoniumchloride or arginine monohydrochlo-ride, although these are contraindi-
cated in hepatic and renal disease,respectively. In obstructive vomitingor nasogastric aspiration, the loss ofacid may be offset by providing an
adequate supply of chloride salt, 1 to2 mEq/kg per day. Such patients often
have a deficit of potassium, whichshould be corrected. In hyperaldos-
teronism, an antagonist such asspironolactone will correct the hyper-
tension and the hypokalemia andrestore a normal acid-base status.
Amiloride may be equally effective.
Hypokalemia and alkalosis areobserved in Bartter syndrome, which
is characterized by hyperreninemichyperaldosteronism and hypersecre-tion of renal prostaglandins. These
may respond to indomethacin, butadditional KC1 may be needed. InCushing syndrome, therapy is direct-ed at the underlying process.
Respiratory Acidosis
Respiratory acidosis is induced by an
increase in Pco2, which lowers plas-ma pH rapidly. Causes include airwayobstruction, anatomic abnormalitiesthat compromise the movement of thethoracic cage, CNS depression orimmaturity, and neuromuscular
defects. Hypercapnea per se is notnearly as detrimental as the hypox-
emia that usually accompanies thesedisorders. However, patients whohave the Pickwickian syndrome(massive obesity, ineffectual respira-tory exchange) may exhibit somno-lence, hypertension, and even retinal
edema as a consequence of hypercap-nea. Intervention is required to cor-rect or compensate for the underlyingcausal process; alkali administrationis not indicated in the setting of purerespiratory acidosis.
Respiratory AlkalosisRespiratory alkalosis is caused by adecrease in PCO2, the result of hyper-ventilation. Acute respiratory alkalo-
sis from hyperventilation inducesdizziness, confusion, and rarely,seizures. These signs and symptoms
FLUIDS & ELECTROLYTESClinical Aspects
result from acutely decreased cerebral
blood flow, which is less prominentin chronic respiratory alkalosis. Thecauses of respiratory alkalosis include
those that can lead to hyperventila-tion, various CNS disorders, and psy-
chobehavioral disturbances . Inter-vention is directed toward correcting
the underlying causal process. Inacute hyperventilation, rebreathinginto a bag will decrease the severityof symptoms.
ConclusionIn our experience, as many mistakesare made by improper monitoring ofthe patient as in the initial diagnosis.
Patients differ widely both in symp-
toms and signs and in their responsesto treatment. Hence, the physician,
after making a presumptive diagnosisand deciding on a course of therapy,must monitor the patient’s responsecarefully. In this way, mistakes injudgment can be recognized promptlyand appropriate corrections made in
the treatment regime.
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SUGGESTED READINGCasteels HB, Fiedorek SC. Oral rehydration
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Nicholas Jospe and Gilbert ForbesClinical Aspects−−BACK TO BASICS: Fluids and Electrolytes
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