23 Fluid and Electrolyte

Management
Emily Whitesel

KEY POINTS
• Transition from fetal to neonatal life is associated with significant
changes in water and electrolyte homeostatic control.
• Sources of water loss in the neonate include kidneys, skin, and lungs.
• Preterm infants are most vulnerable to fluid and electrolyte imbalance.
• Assessment and management of fluid requirements are essential
components of newborn care.

Careful fluid and electrolyte management in term and preterm infants is an essential
component of neonatal care. Developmental changes in body composition in con-
junction with functional changes in skin, renal, and neuroendocrine systems account
for the fluid balance challenges faced by neonatologists on a daily basis. Fluid man-
agement requires the understanding of several physiologic principles.

I. DISTRIBUTION OF BODY WATER

A. General principles. Transition from fetal to newborn life is associated with
major changes in water and electrolyte homeostatic control. Before birth,
the fetus has constant supply of water and electrolytes from the mother
across the placenta. After birth, the newborn assumes responsibility for its
own fluid and electrolyte homeostasis. The body composition of the fetus
changes during gestation with a smaller proportion of body weight being
composed of water as gestation progresses.
B. Definitions
1. Total body water (TBW) 5 intracellular fluid (ICF) 1 extracellular
fluid (ECF) (Fig. 23.1)
2. ECF is composed of intravascular and interstitial fluid.
3. Insensible water loss (IWL) can be estimated by the following equation
5 fluid intake 2 urine output 2 ( D weight); however, unknown and
unmeasurable factors also need to be considered.
C. Perinatal changes in TBW. A proportion of diuresis in both term and preterm
infants (a decrease of 0.8 z scores) during the first days of life should be regarded
as physiologic. However, excessive weight loss should be minimized and coun-
tered by providing appropriate nutritional support during this initial transition.
301

0301-0317_Hansen9e_CH23.indd 301 02/08/2022 5:10 AM

 302    F l u i d a n d E l e c t r o l y te M a n a g eme n t



,QWUDFHOOXODU:DWHU



([WUDFHOOXODU:DWHU

 0LQHUDOV
)DW
DQG2WKHU
3URWHLQ

   J

   
)HWDO:HLJKW*HVWDWLRQDO$JHLQ:HHNV
Figure 23.1. Body composition in relation to fetal weight and gestational age. (Reprinted
from Dweck HS. Feeding the prematurely born infant. Fluids, calories, and methods of feed-
ing during the period of extrauterine growth retardation. Clin Perinatol 1975;2[1]:183–202.
­Copyright © 1975 Elsevier. With permission. Data from Widdowson EM. Growth and com-
position of the fetus and newborn. In: Assali NS, ed. Biology of Gestation. Vol 2. New York, NY:
Academic Press; 1968.)

At lower gestational ages, ECF accounts for a greater proportion of birth weight
(see Fig. 23.1). Therefore, very low birth weight (VLBW) infants lose a greater
percentage of birth weight to maintain ECF proportions equivalent to those of
term infants. Although fluid overload is a potential concern for evolving chronic
lung disease (CLD), nutritional support is necessary to optimize neurodevelop-
ment, and a careful balance must be maintained between allowing appropriate
physiologic diuresis and excessive weight loss.
D. Sources of water loss
1. Renal losses. Renal function matures with increasing gestational age.
Immature sodium (Na) and water homeostasis is common in the
preterm infant. Contributing factors leading to varying urinary water
and electrolyte losses include the following:
a. Decreased glomerular filtration rate (GFR)
b. Reduced proximal and distal tubule Na reabsorption
c. Decreased capacity to concentrate or dilute urine
d. Decreased bicarbonate, potassium (K), and hydrogen ion secretion
2. Extra renal losses. In VLBW infants, IWL can exceed 150 mL/kg/day
owing to increased environmental and body temperatures, skin breakdown,
radiant warmers, phototherapy, and extreme prematurity (Table 23.1).
Respiratory water loss increases with decreasing gestational age and with
increasing respiratory rate; in intubated infants, inadequate humidification
of the inspired gas may lead to increased IWL. Other fluid losses that should
be replaced if amount is deemed significant include stool (diarrhea or os-
tomy drainage), cerebrospinal fluid (from ventriculotomy or serial lumbar
punctures), and nasogastric tube or thoracostomy tube drainage.

0301-0317_Hansen9e_CH23.indd 302 02/08/2022 5:10 AM

 Fluid Electrolytes Nutrition, Gastrointestinal, and Renal Issues    303

Table 23.1. Insensible Water Loss (IWL)

Birth Weight (g) IWL (mL/kg/day)

750–1,000 82
1,001–1,250 56
1,251–1,500 46
.1,501 26
Values represent mean IWL for infants in incubators during the first week of life. IWL is
increased by phototherapy (up to 40%), radiant warmers (up to 50%), and fever. IWL is
decreased by the use of humidified gas with respirators and heat shields in incubators.
Source: Bell EF, Gray JC, Weinstein MR, et al. The effects of thermal environment on heat
balance and insensible water loss in low-birth-weight infants. J Pediatr 1980;96:452–459;
Fanaroff AA, Wald M, Gruber HS, et al. Insensible water loss in low birth weight infants.
Pediatrics 1972;50(2):236–245; and Okken A, Jonxis JH, Rispens P, et al. Insensible water loss
and metabolic rate in low birthweight newborn infants. Pediatr Res 1979;13(9):1072–1075.

Incubators for newborn infants are being designed to improve

maintenance of warmth and humidity and may lead to decreased IWL
(e.g., the Giraffe Isolette).

II. ASSESSMENT OF FLUID AND ELECTROLYTE STATUS

A. History
1. Maternal. The newborn’s fluid and electrolyte status partially reflects
maternal hydration status and drug administration. Excessive use of
oxytocin, diuretics, or hyponatremic intravenous (IV) fluid can lead to
maternal and fetal hyponatremia. Antenatal steroids may increase skin
maturation, subsequently decreasing IWL and the risk of hyperkalemia.
2. Fetal/perinatal. The presence of oligohydramnios may be associated
with congenital renal dysfunction, including renal agenesis, polycystic
kidney disease, or posterior urethral valves. Severe in utero hypoxemia
or birth asphyxia may lead to acute tubular necrosis.
B. Physical examination
1. Change in body weight. Acute changes in an infant’s weight generally re-
flect a change in TBW. The compartment affected will depend on the ges-
tational age and clinical course of the infant. For example, long-term use
of paralytic agents and peritonitis may lead to increased interstitial fluid
volume and increased body weight but decreased intravascular volume.
Therefore, weight should be measured at least daily with consideration for
twice a day weights in the extremely low gestational age newborn.
2. Skin and mucosal manifestations. Altered skin turgor, sunken anterior
fontanelle, and dry mucous membranes are essential to note on the phys-
ical exam but are not sensitive indicators of fluid or electrolyte balance.

0301-0317_Hansen9e_CH23.indd 303 02/08/2022 5:10 AM

 304    F l u i d a n d E l e c t r o l y te M a n a g eme n t

3. Cardiovascular. Tachycardia can result from hypovolemia or from ECF

excess (e.g., heart failure). Capillary refill time can be delayed with re-
duced cardiac output or peripheral vasoconstriction. Hepatomegaly can
occur with increased ECF volume. Blood pressure changes occur late in
the sequence of responses to reduced cardiac output.
C. Laboratory studies
1. Serum electrolytes and plasma osmolarity reflect the composition and
tonicity of the ECF. Frequent monitoring, up to every 6 hours, should
be done in the extremely low birth weight (ELBW) infants during the
first few days of life owing to high IWL.
2. Fluid balance with input and output measurements should be mon-
itored. Normal urine output is 1 to 3 mL/kg/hour. However, ELBW
infants typically pass through three phases, with an initial prediuretic
or oliguric phase, followed by a diuresis, before transitioning to a
postdiuretic phase. With ECF depletion (dehydration), urine output
may fall to ,1 mL/kg/hour. However, in neonates with immature
renal function, urine output may not decrease despite ECF volume
depletion.
3. Urine electrolytes and specific gravity (SG) can reflect renal capacity
to concentrate or dilute urine and reabsorb or excrete Na. Increases in
SG can occur when the infant is receiving decreased fluids, has decreased
urine output, or is spilling glucose. Neither urine electrolytes nor SG is
very helpful when infant is on diuretics.
4. Fractional excretion of Na (FENa) reflects the balance between glo-
merular filtration and tubular reabsorption of Na. However, the utility
is limited in preterm infants given decreased tubular Na reabsorption,
and FENa increases with decreasing gestational age.
FENa 5 (urine Na 3 plasma creatinine) / (plasma Na 3
urine creatinine) 3 100
a. Level of ,1% indicates prerenal factors reducing renal blood flow.
b. Level of 2.5% occurs with acute kidney injury (AKI).
c. Level of .2.5% is frequently seen in infants of ,32 weeks’ gestation.
5. Blood urea nitrogen (BUN) and serum creatinine (Cr) values provide
indirect information about ECF volume and GFR. However, these
values can be challenging to interpret because initial levels are affected
by maternal levels and placental clearance. Preterm infants have elevated
values at birth that tend to fall over the first few weeks of life, making
baseline levels hard to assess in the setting of physiologic change. De-
spite these challenges, neonates are at risk for AKI and serum Cr should
be assessed initially and trended during any event that may carry an
additional risk for AKI, such as a hemodynamically significant patent
ductus arteriosus (PDA), sepsis, or necrotizing enterocolitis (NEC).
6. Arterial pH, carbon dioxide tension (partial pressure of carbon
dioxide [PCO2]), and Na bicarbonate determinations can provide
indirect evidence of intravascular volume depletion because poor tissue
perfusion leads to high anion gap metabolic acidosis (lactic acidosis).

0301-0317_Hansen9e_CH23.indd 304 02/08/2022 5:10 AM

 Fluid Electrolytes Nutrition, Gastrointestinal, and Renal Issues    305

Table 23.2. Initial Fluid Therapy*

Fluid Rate (mL/kg/day)

Birth Dextrose
Weight (kg) (g/100 mL) ,24 hours 24–48 hours .48 hours
†
,1 5–10 100–150 120–150 140–190
1–1.5 10 80–100 100–120 120–160
.1.5 10 60–80 80–120 120–160
*Infants in humidified incubators. Infants under radiant warmers usually require higher
initial fluid rates.
†
Very low birth weight infants frequently require even higher initial rates of fluid adminis-
tration and frequent reassessment of serum electrolytes, urine output, and body weight.

III. MANAGEMENT OF FLUIDS AND ELECTROLYTES. The goal of early man-

agement is to allow physiologic ECF loss over the several days of life, while
minimizing weight loss, all while maintaining normal tonicity and intravas-
cular volume as reflected by blood pressure, heart rate, urine output, serum
electrolyte levels, and pH. Subsequent fluid management should maintain
water and electrolyte balance, including requirements for body growth.
A. The term infant. Body weight decreases by 3% to 5% over the first 5 to
6 days. Subsequently, fluids should be adjusted so that changes in body
weight are consistent with caloric intake. Clinical status should be moni-
tored for maldistribution of water (e.g., edema). Na supplementation is not
usually required in the first 24 hours unless ECF expansion is necessary.
Small for gestational age term infants may require early Na supplementation
to maintain adequate ECF volume.
B. The premature infant. Anticipate weight loss over the initial several days.
Table 23.2 summarizes initial fluid therapy. Then, adjust fluids to main-
tain stable weight until an anabolic state is achieved and growth occurs.
Frequently assess response to fluid and electrolyte therapy during the first
2 days of life. Physical examination, urine output, SG, and serum elec-
trolyte determinations may be required initially as frequently as every
6 hours in infants ,1,000 g (see section VIII.A).
Water loss through skin and urine may exceed 200 mL/kg/day, which
can represent up to one-third of TBW. IV Na supplementation is not
required for the first 24 hours unless ECF volume loss exceeds 5% of body
weight per day (see Chapter 13).

IV. APPROACH TO DISORDERS OF NA AND WATER BALANCE. Abnormali-

ties can be grouped into disorders of tonicity or ECF volume. The conceptual
approach to disorders of tonicity (e.g., hyponatremia) depends on whether the

0301-0317_Hansen9e_CH23.indd 305 02/08/2022 5:10 AM

 306    F l u i d a n d E l e c t r o l y te M a n a g eme n t

newborn exhibits normal ECF (euvolemia), ECF depletion (dehydration), or

ECF excess (edema).
A. Isonatremic disorders
1. Dehydration
a. Predisposing factors frequently involve equivalent losses of Na and
water (through thoracostomy, nasogastric, or ventriculostomy drainage)
or third-space losses that accompany peritonitis, gastroschisis, or om-
phalocele. Renal Na and water losses in the VLBW infant can lead to
hypovolemia despite normal body tonicity.
b. Diagnosis. Dehydration is usually manifested by weight loss, decreased
urine output, and increased urine SG. However, infants of ,32 weeks’
gestation may not demonstrate oliguria in response to hypovolemia. Poor
skin turgor, tachycardia, hypotension, metabolic acidosis, and increasing
BUN may coexist. A low FENa (,1%) is usually only seen in infants of
.32 weeks’ gestational age (see section II.C.4).
c. Therapy. Administer Na and water to first correct deficits and
then adjust to equal maintenance needs plus ongoing losses. Acute is-
onatremic dehydration may require IV infusion of 10 mL/kg of NS if
acute weight loss is .10% of body weight with signs of poor cardiac
output.
2. Edema
a. Predisposing factors include excessive isotonic fluid administration,
heart failure, sepsis, and neuromuscular paralysis.
b. Diagnosis. Clinical signs include periorbital and extremity edema,
increased weight, and hepatomegaly.
c. Therapy includes Na restriction (to decrease total-body Na) and
water restriction (depending on electrolyte response).
B. Hyponatremic disorders (Table 23.3). Consider factitious hyponatre-
mia due to hyperlipidemia or hypoosmolar hyponatremia due to osmotic
agents. True hypoosmolar hyponatremia can then be evaluated.
1. Hyponatremia due to ECF volume depletion
a. Predisposing factors include diuretic use, osmotic diuresis (glycos-
uria), VLBW with renal water and Na wasting, adrenal or renal tubular
salt-losing disorders, gastrointestinal losses (vomiting, diarrhea), and
third-space losses of ECF (skin sloughing, early NEC).
b. Diagnosis. Decreased weight, poor skin turgor, tachycardia, rising
BUN, and metabolic acidosis are frequently observed. If renal function
is mature, the newborn may develop decreased urine output, increased
urine SG, and a low FENa.
c. Therapy. If possible, reduce ongoing Na loss. Administer Na and
water to replace deficits and then adjust to match maintenance needs
plus ongoing losses.
2. Hyponatremia with normal ECF volume
a. Predisposing factors include excess fluid administration and the
syndrome of inappropriate antidiuretic hormone (SIADH) secretion.
Factors that cause SIADH include pain, opiate administration, intraven-
tricular hemorrhage (IVH), asphyxia, meningitis, pneumothorax, and
positive pressure ventilation.

0301-0317_Hansen9e_CH23.indd 306 02/08/2022 5:10 AM

 Fluid Electrolytes Nutrition, Gastrointestinal, and Renal Issues    307

Table 23.3. Hyponatremic Disorders

Clinical Diagnosis Etiology Therapy

Factitious hyponatremia/ Hyperlipidemia
pseudohyponatremia
Hypertonic hyponatremia/ Mannitol
hyperosmolar hyponatremia
Hyperglycemia
ECF volume normal Syndrome of inappropriate Restrict
antidiuretic hormone (SIADH) water intake.
Pain
Opiates
Excess intravenous fluids
ECF volume deficit Diuretics Increase Na
intake.
Late-onset hyponatremia of
prematurity
Congenital adrenal hyperplasia
Severe glomerulotubular imbalance
(immaturity)
Renal tubular acidosis
Gastrointestinal losses
Necrotizing enterocolitis (third-
space loss)
ECF volume excess Heart failure Restrict
water intake.
Neuromuscular blockade (e.g.,
pancuronium)
Sepsis
ECF, extracellular fluid; Na, sodium.

b. Diagnosis of SIADH. Weight gain usually occurs without edema. Ex-

cessive fluid administration without SIADH results in low urine SG and
high urine output. In contrast, SIADH leads to decreased urine output
and increased urine osmolarity. Urinary Na excretion in infants with
SIADH varies widely and reflects Na intake. The diagnosis of SIADH
presumes no volume-related stimulus to antidiuretic hormone (ADH)

0301-0317_Hansen9e_CH23.indd 307 02/08/2022 5:10 AM

 308    F l u i d a n d E l e c t r o l y te M a n a g eme n t

release, such as reduced cardiac output or abnormal renal, adrenal, or thy-

roid function.
c. Therapy. Water restriction is therapeutic unless (i) serum Na con-
centration is less than approximately 120 mEq/L or (ii) neurologic signs
such as obtundation or seizure activity develop. In these instances, hy-
pertonic Na chloride (NaCl) (3%) (1 to 3 mL/kg initial dose) should
be used. Fluid restriction alone can be used once serum Na concentra-
tion is .120 mEq/L and neurologic signs abate.
3. Hyponatremia due to ECF volume excess
a. Predisposing factors include sepsis with decreased cardiac output,
late NEC, heart failure, abnormal lymphatic drainage, and neuromuscu-
lar paralysis.
b. Diagnosis. Weight increase with edema is observed. Decreasing urine
output, increasing BUN and urine SG, and a low FENa are often present
in infants with mature renal function.
c. Therapy. Treat the underlying disorder and restrict water to allevi-
ate hypotonicity. Na restriction and improving cardiac output may be
beneficial.
C. Hypernatremic disorders
1. Hypernatremia with normal or deficient ECF volume
a. Predisposing factors include increased renal and IWL in VLBW in-
fants. Skin sloughing can accelerate water loss. ADH deficiency second-
ary to IVH can occasionally exacerbate renal water loss.
b. Diagnosis. Weight loss, tachycardia and hypotension, metabolic
acidosis, decreasing urine output, and increasing urine SG may occur.
Urine may be dilute if the newborn exhibits central or nephrogenic dia-
betes insipidus.
c. Therapy. Increase free water administration to reduce serum Na no
faster than 1 mEq/kg/hour. If signs of ECF depletion or excess develop,
adjust Na intake. Hypernatremia does not necessarily imply excess
total-body Na. For example, in the VLBW infant, hypernatremia in
the first 24 hours of life is almost always due to free water deficits
(see section VIII.A.1).
2. Hypernatremia with ECF volume excess
a. Predisposing factors include excessive isotonic or hypertonic fluid
administration, especially in the face of reduced cardiac output.
b. Diagnosis. Weight gain associated with edema is observed. The in-
fant may exhibit normal heart rate, blood pressure, and urine output and
SG but an elevated FENa.
c. Therapy. Restrict Na administration.

V. OLIGURIA. Oliguria exists if urine flow is ,1 mL/kg/hour. Although delayed

micturition in a healthy infant is not of concern until 24 hours after birth,
urine output in a critically ill infant should be assessed by 8 to 12 hours of
life, using urethral catheterization if indicated. Diminished urine output may
reflect abnormal prerenal, renal parenchymal, or postrenal factors (Table 23.4).
Neonatal AKI is often multifactorial, with prerenal causes being the most com-
mon, including hypotension, hypovolemia, intravascular volume depletion,

0301-0317_Hansen9e_CH23.indd 308 02/08/2022 5:10 AM

 Fluid Electrolytes Nutrition, Gastrointestinal, and Renal Issues    309

Table 23.4. Etiologies of Oliguria

Prerenal Renal Parenchymal Postrenal

Decreased inotropy Acute tubular necrosis Posterior urethral

valves

Ischemia (hypoxia, hypovolemia)

Decreased preload Disseminated intravascular Neuropathic bladder

coagulation

Renal artery or vein thrombosis

Increased peripheral Nephrotoxin Prune belly syndrome

resistance

Congenital malformation Uric acid nephropathy

  Polycystic disease

 Agenesis

 Dysplasia

and sepsis. It is important to exclude other potentially treatable etiologies (see

Chapter 28). In VLBW infants, oliguria may be normal in the first 24 hours of
life (see section VIII.A.1).
A. History and physical examination. Screen the maternal and infant history
for maternal diabetes (renal vein thrombosis), birth asphyxia (acute tubu-
lar necrosis), and oligohydramnios (Potter syndrome). Force of the infant’s
urinary stream (posterior urethral valves), rate and nature of fluid admin-
istration and urine output, and nephrotoxic drug use (aminoglycosides,
indomethacin, furosemide) should be evaluated. Physical examination
should determine blood pressure and ECF volume status; evidence of car-
diac disease, abdominal masses, or ascites; and the presence of any congen-
ital anomalies associated with renal abnormalities (e.g., Potter syndrome,
epispadias).
B. Diagnosis
1. Initial laboratory examination should include urinalysis, BUN, Cr,
and FENa determinations. These aid in diagnosis and provide baseline
values for further management.
2. Fluid challenge, consisting of a total of 20 mL/kg of NS, is adminis-
tered as two infusions at 10 mL/kg/hour if no suspicion of structural
heart disease or heart failure exists. Decreased cardiac output not re-
sponsive to ECF expansion may require the institution of inotropic/
chronotropic pressor agents. Some may consider low-dose dopamine to
attempt to augment renal blood flow and urine output (see Chapter 40).

0301-0317_Hansen9e_CH23.indd 309 02/08/2022 5:10 AM

 310    F l u i d a n d E l e c t r o l y te M a n a g eme n t

3. If no response to fluid challenge occurs, one may induce diuresis with

furosemide 1 to 2 mg/kg IV.
4. Patients who are unresponsive to increased cardiac output and diuresis
should be evaluated with an abdominal ultrasonography to define
renal, urethral, and bladder anatomy. Other forms of imaging such as
a voiding cystourethrography, IV pyelography, or angiography may be
required (see Chapter 28).
C. Management. Prerenal oliguria should respond to increased cardiac output.
Postrenal obstruction requires urologic consultation, with possible urinary
diversion and surgical correction. If parenchymal AKI is suspected, minimize
excessive ECF expansion and electrolyte abnormalities. If possible, eliminate
reversible causes of declining GFR, such as nephrotoxic drug use.
1. Monitor daily weight, input and output, and BUN, Cr, and serum
electrolytes.
2. Fluid restriction. Replace insensible fluid loss plus urine output. With-
hold K supplementation unless hypokalemia develops. Replace urinary
Na losses unless edema develops.
3. Adjust dosage and frequency of drugs eliminated by renal excretion.
Monitor serum drug concentrations to guide drug-dosing intervals.
4. Peritoneal or hemodialysis may be indicated in patients whose GFR
progressively declines causing complications related to ECF volume or
electrolyte abnormalities (see Chapter 28).

VI. METABOLIC ACID–BASE DISORDERS

A. Normal acid–base physiology. Normal sources of acid production include
the metabolism of amino acids containing sulfur and phosphate as well as
hydrogen ion released from bone mineralization. Intravascular buffers include
bicarbonate, phosphate, and intracellular hemoglobin. Maintenance of nor-
mal pH depends on excretion of volatile acid (e.g., carbonic acid) from the
lungs, skeletal exchange of cations for hydrogen, and renal regeneration and
reclamation of bicarbonate. Kidneys contribute to maintenance of acid–base
balance by reabsorbing the filtered load of bicarbonate, secreting hydrogen
ions as titratable acidity (e.g., H2PO4), and excreting ammonium ions.
B. Metabolic acidosis (see Chapter 60). Metabolic acidosis results from exces-
sive loss of buffer or from an increase of volatile or nonvolatile acid in the
extracellular space.
1. Anion gap. Metabolic acidosis can result from accumulation of acid or
loss of buffering equivalents. Anion gap determination will suggest mech-
anism. Na, Cl, and bicarbonate are the primary ions of the extracellular
space and exist in approximately electroneutral balance. The anion gap,
calculated as the difference between the Na concentration and sum of the
Cl and bicarbonate concentrations, reflects the unaccounted-for anion
composition of the ECF. An increased anion gap indicates an accumula-
tion of organic acid, whereas a normal anion gap indicates a loss of buffer
equivalents. Normal values for the neonatal anion gap are 5 to 15 mEq/L
and vary directly with serum albumin concentration.

0301-0317_Hansen9e_CH23.indd 310 02/08/2022 5:10 AM

 Fluid Electrolytes Nutrition, Gastrointestinal, and Renal Issues    311

Table 23.5. Metabolic Acidosis

Increased Anion Gap (.15 mEq/L) Normal Anion Gap (,15 mEq/L)
Acute renal failure Renal bicarbonate loss
Inborn errors of metabolism   Renal tubular acidosis
Lactic acidosis  Acetazolamide
Late metabolic acidosis   Renal dysplasia
Toxins (e.g., benzyl alcohol) Gastrointestinal bicarbonate loss
 Diarrhea
 Cholestyramine
  Small-bowel drainage
Dilutional acidosis
Hyperalimentation acidosis

2. Metabolic acidosis associated with an increased anion gap

(.15 mEq/L). Disorders (Table 23.5) include renal failure, inborn
errors of metabolism, lactic acidosis, late metabolic acidosis, and toxin
exposure. Lactic acidosis results from diminished tissue perfusion and
resultant anaerobic metabolism in infants with asphyxia or severe car-
diorespiratory disease. Late metabolic acidosis typically occurs during
the second or third week of life in premature infants who ingest high
casein-containing formulas, where intake is in excess of renal clearance.
Although no longer common now that infant formulas are not casein
based, it still may occur, particularly with IV nutrition.
3. Metabolic acidosis associated with a normal anion gap (,15 mEq/L)
results from bicarbonate loss through the gastrointestinal system or the
kidneys (see Table 23.5). Premature infants ,32 weeks’ gestation fre-
quently manifest a proximal or distal renal tubular acidosis (RTA). Urine
pH persistently .7 in an infant with metabolic acidosis suggests a distal
RTA, with an inability to secrete hydrogen ions. Proximal RTAs results
from reduced bicarbonate reabsorption, although urinary pH for a proxi-
mal RTA may vary.
4. Therapy. Whenever possible, treat the underlying cause. Lactic
acidosis due to low cardiac output or due to decreased peripheral ox-
ygen delivery should be treated with specific measures. Treat normal
anion gap metabolic acidosis by decreasing the rate of bicarbonate
loss (e.g., decreased small-bowel drainage) or providing buffer equiv-
alents. IV Na bicarbonate or Na acetate (which is compatible with
calcium [Ca] salts) is more commonly used to treat severe acidosis.
Oral buffer supplements can include citric acid (Bicitra) or Na citrate

0301-0317_Hansen9e_CH23.indd 311 02/08/2022 5:10 AM

 312    F l u i d a n d E l e c t r o l y te M a n a g eme n t

(1 to 3 mEq/kg/day). Estimate bicarbonate deficit from the following

formula:
Deficit 5 0.4 3 body weight 3 (desired bicarbonate 2
actual bicarbonate)
The premature infant’s acid–base status can change rapidly, and
frequent monitoring is warranted. The infant’s ability to tolerate an
increased Na load and to metabolize acetate is an important variable that
influences acid–base status during treatment.
C. Metabolic alkalosis. Metabolic alkalosis is characterized by an elevation
in serum bicarbonate. Major causes of metabolic alkalosis can be cate-
gorized as hydrogen loss through the gastrointestinal tract (e.g., emesis,
gastric suctioning, congenital chloride diarrhea), renal hydrogen loss
(loop or thiazide diuretics, primary mineralocorticoid excess, Bartter/
Gitelman syndrome, chronic hypercarbia), severe hypokalemia result-
ing in intracellular hydrogen shift, alkali administration in the setting
of impaired renal function, and contraction alkalosis. The etiology of
metabolic alkalosis can be clarified by determining urinary Cl concen-
tration. Alkalosis accompanied by ECF depletion is associated with de-
creased urinary Cl, whereas states of mineralocorticoid excess are usually
associated with increased urinary Cl (Table 23.6). Treat the underlying
disorder.

VII. DISORDERS OF K BALANCE. K is the fundamental intracellular cation.

Serum K concentrations do not necessarily reflect total-body K because
extracellular and intracellular K distribution also depends on the pH of
body compartments. An increase of 0.1 pH unit in serum results in
approximately 0.6 mEq/L fall in serum K concentration due to an
intracellular shift of K ions. Total-body K is regulated by balancing K

Table 23.6. Metabolic Alkalosis

Low Urinary Cl (,10 mEq/L) High Urinary Cl (.20 mEq/L)

Diuretic therapy (late) Bartter syndrome with mineralocorticoid
excess
Acute correction of chronically Alkali administration
compensated respiratory acidosis
Nasogastric suction Massive blood product transfusion
Vomiting Diuretic therapy (early)
Secretory diarrhea Hypokalemia
Cl, chloride.

0301-0317_Hansen9e_CH23.indd 312 02/08/2022 5:10 AM

 Fluid Electrolytes Nutrition, Gastrointestinal, and Renal Issues    313

intake (normally 1 to 2 mEq/kg/day) and excretion through urine and the

gastrointestinal tract.
A. Hypokalemia is usually asymptomatic; however, it can lead to arrhythmias,
ileus, renal concentrating defects, and lethargy in the newborn.
1. Predisposing factors include nasogastric or ileostomy drainage, chronic
diuretic use, and renal tubular defects.
2. Diagnosis. Obtain serum electrolytes, BUN, Cr, as well as urine electro-
lytes, pH, and an electrocardiogram (ECG) to detect possible conduction
defects (prolonged QT interval and U waves).
3. Therapy. Reduce renal or gastrointestinal losses of K. Gradually in-
crease intake of K as needed.
B. Hyperkalemia. The normal serum K level in a nonhemolyzed blood spec-
imen at normal pH is 3.5 to 5.5 mEq/L; symptomatic hyperkalemia may
begin at a serum K level .6 mEq/L.
1. Predisposing factors. Hyperkalemia can occur unexpectedly in any patient
but should be anticipated and screened for in the following scenarios:
a. Increased K release secondary to tissue destruction, trauma, cephalhe-
matoma, hypothermia, bleeding, intravascular or extravascular hemoly-
sis, asphyxia/ischemia, and IVH
b. Decreased K clearance due to renal failure, oliguria, hyponatremia,
and congenital adrenal hyperplasia
c. Miscellaneous associations including dehydration, birth weight
,1,500 g (see section VIII.A.2), blood transfusion, inadvertent excess
(KCl) administration, CLD with KCl supplementation (see section
VIII.B), and exchange transfusion.
2. Diagnosis. Up to 50% of VLBW infants born before 25 weeks’ gestation
manifest serum K levels .6 mEq/L in the first 48 hours of life (see section
VIII.A.2). However, with sudden unexpected hyperkalemia in the neona-
tal intensive care unit (NICU), medication error must be considered. Ob-
tain serum and urine electrolytes, serum pH, and Ca concentrations. The
hyperkalemic infant may be asymptomatic or may present with a spec-
trum of signs including bradyarrhythmias or tachyarrhythmias, cardiovas-
cular instability, or collapse. The ECG findings progress with increasing
serum K from peaked T waves (increased rate of repolarization), flattened
P waves and increasing PR interval (suppression of atrial conductivity), to
QRS widening and slurring (conduction delay in ventricular conduction
tissue as well as in the myocardium itself), and finally, supraventricular/
ventricular tachycardia, bradycardia, or ventricular fibrillation. The ECG
findings may be the first indication of hyperkalemia (see Chapter 41).
3. Management. Once hyperkalemia is diagnosed, remove all sources
of exogenous K (change all IV solutions and analyze for K con-
tent), rehydrate the patient if necessary, and eliminate arrhythmia-­
promoting factors. Although limited studies are available addressing
the pharmacology and treatment of neonatal hyperkalemia, the ap-
proach consists of three components:
a. Goal 1: stabilization of cardiac membrane. This can be accom-
plished by Ca administration. Ca gluconate (10%) given carefully at a

0301-0317_Hansen9e_CH23.indd 313 02/08/2022 5:10 AM

 314    F l u i d a n d E l e c t r o l y te M a n a g eme n t

starting dose of 60 to 100 mg/kg/dose may be the most useful in the

NICU. Dosing may be repeated as needed. Treatment with hypertonic
NaCl solution has also been reported in patients who are both hyperka-
lemic and hyponatremic but is not done routinely. Use of antiarrhyth-
mic agents may be considered for refractory ventricular tachycardia (see
Chapter 41).
b. Goal 2: dilution and intracellular shifting of K
i. Increased serum K in the setting of dehydration should respond to
fluid resuscitation.
ii. Insulin enhances intracellular K uptake by direct stimulation of
the membrane-bound Na–K ATPase. Neonates are sensitive to
the effects of insulin requiring concomitant glucose administra-
tion to maintain normal blood glucose concentration and fre-
quent monitoring of serum or blood glucose levels. This therapy
may begin with a bolus of insulin and glucose or may start with
an insulin and glucose infusion. A continuous IV infusion of
insulin should be started within the range of 0.01 to 0.1 units/
kg/hour. The usual ratio is 1 unit of insulin for every 2 to 4 g
of dextrose for a continuous infusion. If considering an ini-
tial bolus of insulin, typical dosing is 0.05 units/kg of human
regular insulin in combination with dextrose bolus. The usual
ratio is 1 unit of insulin for every 5 g of dextrose for intermit-
tent IV doses of insulin. To minimize the effect of binding to IV
tubing, insulin diluted in dextrose 10% in water (D10W) may be
flushed through the tubing. Adjustments in infusion rate of either
glucose or insulin in response to hyperglycemia or hypoglycemia
may be simplified if the two solutions are prepared individually
(see Chapter 24).
iii. b2-Adrenergic stimulation works by driving the K intracellularly
by stimulating the Na–K ATPase. Although a paucity of neonatal/
preterm data exists, b stimulation can be an effective and readily
available therapy in the treatment of acute hyperkalemia, which
appears to be well tolerated.
iv. Acidosis may increase serum K by shifting the balance of the in-
tracellular K-for-hydrogen-ion exchange, leading to K movement
extracellularly and worsening hyperkalemia. In theory, when aci-
dosis is corrected, the opposite will occur, shifting K back intracel-
lularly. If acidosis is present, Na bicarbonate 1 to 2 mEq/kg IV
may be used, although the resultant pH change may not be suf-
ficient to markedly shift K ions. Theoretically, every 0.1 pH unit
increase leads to a decrease of 0.6 mEq/L in serum K. However,
little evidence exits to support efficacy in neonates, with known
risks of Na bicarbonate administration, including the risk of IVH
in premature neonates.
c. Goal 3: enhanced K excretion. As the therapies earlier are transient,
steps should be taken to remove K as the infant is being stabilized.
i. Diuretic therapy (e.g., furosemide 1 mg/kg IV) may increase
K excretion by increasing flow and Na delivery to the distal
tubules. This is a potentially effective way to eliminate K from
the body.

0301-0317_Hansen9e_CH23.indd 314 02/08/2022 5:10 AM

 Fluid Electrolytes Nutrition, Gastrointestinal, and Renal Issues    315

ii. Double volume exchange transfusion is another potentially life-

saving option (see Chapter 26) that has been reported in the past.
However, it comes with its own risks, requires expertise, and takes
time to prepare.
iii. Cation exchange resins such as sodium polystyrene sulfonate
(Kayexalate) provide another mechanism through which K may
be excreted. It works by enhancing K excretion through the gut
through the exchange of Na for K ions. These resins can be ad-
ministered orally or rectally. However, they have been studied
primarily in adults, and raise a number of safety concerns in the
neonatal population. Overall, the efficacy in the neonate is ques-
tionable, and despite animal studies showing improved safety in
updated suspensions (sorbitol-free), there continues to be an in-
creased risk for NEC as well as possible bowel obstruction due
to plug formation. Therefore, any use of Kayexalate in preterm
infants must be done with extreme caution. Oral/PG adminis-
tration of Kayexalate is not recommended in preterm infants
because they are prone to hypomotility and are at risk for
NEC. Should the use of Kayexalate be deemed necessary, then
rectal administration of Kayexalate (1 g/kg/dose) with a reten-
tion time of 15 to 30 minutes is recommended. This may be
effective in lowering serum K levels by approximately 1 mEq/L.
Of note, due to its delayed onset of action, it should not be used
in a situation that requires emergent intervention.
The clinical condition, ECG, and actual serum K level
all affect the choice of therapy for hyperkalemia. Figure 23.2
contains guidelines for treatment of hyperkalemia.

VIII. COMMON CLINICAL SITUATIONS

A. VLBW infant
1. VLBW infants undergo three phases of fluid and electrolyte homeo-
stasis: prediuretic (first day of life), diuretic (second to third day of life),
and postdiuretic (fourth to fifth day of life). Marked diuresis can occur
during the diuretic phase leading to hypernatremia and the need for
frequent serum electrolyte determinations (q6–8h) and increased rates
of parenteral fluid administration. Increased free water loss through
skin and dopamine-associated natriuresis (due to increased GFR) can
further complicate management. Hypernatremia often occurs despite a
total-body Na deficit. Lack of a brisk diuretic phase has been associated
with increased CLD incidence.
In addition, impaired glucose tolerance can lead to hyperglyce-
mia, requiring reduced rates of parenteral glucose infusion (see Chapter
24). This combination frequently leads to administration of reduced
dextrose concentrations in parenteral solutions. Avoid the infusion of
parenteral solutions containing ,200 mOsmol/L (i.e., D3W), to mini-
mize local osmotic hemolysis and thereby reduce renal K load.
2. VLBW infants often develop a nonoliguric hyperkalemia in the first
few days of life. This is caused by a relatively low GFR combined with

0301-0317_Hansen9e_CH23.indd 315 02/08/2022 5:10 AM

 316    F l u i d a n d E l e c t r o l y te M a n a g eme n t

5HPRYH$OO6RXUFHVRI([RJHQRXV3RWDVVLXP

$EQ
&96WDWXV 6XSSRUW&DUGLDF2XWSXW&DOFLXP*OXFRQDWH1D+&2
)XURVHPLGH.D\H[DODWH
1, *OXFRVH,QVXOLQ

$EQ &DOFLXP*OXFRQDWH1D+&2&KHFNIRU$UUK\WKPLD
(&* &DXVHV
5HSHDW(&*
1, $EQ
1,
5HMRLQ$OJRULWKPDW *OXFRVH,QVXOLQ)XURVHPLGH
5HQDO6WDWXV &RQVLGHU5HSHDWLQJ6WHSDERYH
.D\H[DODWH
$EQ
5HQDO6WDWXV .D\H[DODWH)XURVHPLGHLI2OLJXULF
'LDO\VLV'RXEOH9ROXPH([FKDQJH

1,

<HV
>. @!P(T/ 1D+&2)XURVHPLGH*OXFRVH,QVXOLQ
.D\H[DODWH

1R

<HV
2QJRLQJ.5HOHDVH )XURVHPLGH
.D\H[DODWHRU*OXFRVH,QVXOLQ

1R
:DWFKRU)XURVHPLGH

,Q*HQHUDOLI>. @$FFHSWDEOHIRUK&HDVH7KHUDS\EXW&RQWLQXH0RQLWRULQJ

'UXJ'RVHV &DOFLXP*OXFRQDWH ²P/NJ,9

1D+&2 ²P(TNJ,9
)XURVHPLGH PJNJ,9
*OXFRVH,QVXOLQ %ROXV ':P/NJ
+XPXOLQ8NJ
,QIXVLRQ ':²P/NJK
+XPXOLQ8P/':RUDOEXPLQ
P/NJK
.D\H[DODWH JNJ358VHG&DXWLRXVO\LQWKH6HWWLQJRIDQ,PPDWXUH
,VFKHPLF*O7UDFW

Figure 23.2. Treatment of hyperkalemia. CV, cardiovascular; Nl, normal; Abn, abnormal;

NaHCO3, sodium bicarbonate; ECG, electrocardiogram; IV, intravenous; D10W, dextrose in
10% water; GI, gastrointestinal. For a given algorithm outcome, proceed by administering
the entire set of treatments labeled (1). If unsuccessful in lowering [K1] or improving clinical
condition, proceed to the next set of treatments, for example, (2) and then (3).

an intracellular to extracellular K shift due to decreased Na–K ATPase

activity. Postnatal glucocorticoid use may further inhibit Na–K ATPase
activity. Insulin infusion to treat hyperkalemia may be necessary but
elevates the risk of iatrogenic hypoglycemia (see section VII.B for addi-
tional treatment details).
3. Late-onset hyponatremia of prematurity is defined as hyponatremia
that occurs after the second week of life in the growing premature infant
in the setting of a negative Na balance. Failure of the immature renal

0301-0317_Hansen9e_CH23.indd 316 02/08/2022 5:10 AM

 Fluid Electrolytes Nutrition, Gastrointestinal, and Renal Issues    317

tubules to reabsorb filtered Na in a rapidly growing infant contributes

to this condition as well as low Na intake due to the low Na content in
breast milk. Diuretic therapy for babies with CLD may compound these
losses. Late-onset hyponatremia has been reported in up to half of all
preterm infants who are predominately human milk fed by 3 to 4 weeks
of life. Periodic electrolyte measurements should be obtained, starting
2 weeks after achieving full volume enteral feeds. If affected, treatment
with simple Na supplementation (start with 2 mEq/kg/day).
B. Severe CLD (see Chapter 34). CLD requiring diuretic therapy often
leads to hypokalemic, hypochloremic metabolic alkalosis. Affected in-
fants frequently have a chronic respiratory acidosis with partial metabolic
compensation. Subsequently, vigorous diuresis can lead to total-body K and
ECF volume depletion, causing a superimposed metabolic alkalosis. If the
alkalosis is severe, alkalemia (pH .7.45) can supervene and result in cen-
tral hypoventilation. If possible, gradually reduce urinary Na and K loss by
reducing the diuretic dose and/or increase K intake by administration of
KCl (starting at 1 mEq/kg/day). Rarely, administration of ammonium Cl
(0.5 mEq/kg) is required to treat the metabolic alkalosis. Long-term use of
loop diuretics such as furosemide promotes excessive urinary Ca losses and
nephrocalcinosis. Urinary Ca losses may be reduced through concomitant
thiazide diuretic therapy (see Chapter 34).

Suggested Readings
Baumgart S. What’s new from this millennium in fluids and electrolyte management
for the VLBW and ELBW prematures. J Neonatal-Perinatal Med 2009;2(1):1–9.
Bell EF, Gray JC, Weinstein MR, et al. The effects of thermal environment on
heat balance and insensible water loss in low-birth-weight infants. J Pediatr
1980;96:452–459.
Bhatia J. Fluid and electrolyte management in the very low birth weight neonate.
J Perinatol 2006;26(suppl 1):S19–S21.
Bonilla-Félix M. Potassium regulation in the neonate. Pediatr Nephrol
2017;32(11):2037–2049. doi:10.1007/s00467-017-3635-2.
Lindower JB. Water balance in the fetus and neonate. Semin Fetal Neonatal Med
2017;22(2):71–75. doi:10.1016/j.siny.2017.01.002.
Lorenz JM, Kleinman LI, Ahmed G, et al. Phases of fluid and electrolyte homeostasis
in the extremely low birth weight infant. Pediatrics 1995;96(3, pt 1):484–489.
Segar JL. A physiological approach to fluid and electrolyte management of the
preterm infant: review. J Neonatal Perinatal Med 2020;13(1):11–19.

0301-0317_Hansen9e_CH23.indd 317 02/08/2022 5:10 AM