Infants admitted to a neonatal intensive care unit who are unable to exclusively feed orally require careful management of fluid and electrolyte balance. Additional difficulties may
occur if the infant is preterm and if, as frequently happens in babies requiring surgery, there are additional losses from the intestine or the kidneys as a result of a complex surgical problem. When planning maintenance fluid therapy for an infant, all the variables that have already been discussed that may influence fluid requirements must be taken into account.
Any guidelines for fluid and electrolyte therapy must be modified to suit an individual infant’s requirements. Tables 12.1 and 12.2 give some guidelines that may be used and modified appropriately.36
Preterm infants B1.5 kg should be commenced on total parenteral nutrition in the first few hours of life to optimize their nutrition. Further discussion of neonatal enteral and parenteral nutrition is beyond the scope of this chapter.
Table 12.2 Maintenance electrolyte therapy.
Per kg/day
Sodium 24 mmol
Potassium 13 mmol
Calcium 510 mL of 10% calcium gluconate (1.1252.25 mmol calcium) Table 12.1 Fluid requirement in the newborn.
Fluid volume (mL/kg)
Fluid type
Baby nursed in incubator
Day 1 60 10% dextrose/TPN
Day 2 80 Electrolyte solution/10%
dextrose/TPN
Day 3 100 Electrolyte solution/10%
dextrose/TPN
Day 4 120 Electrolyte solution/10%
dextrose/TPN
Day 5 150 Electrolyte solution/10%
dextrose/TPN Baby nursed under radiant warmer
Day 1 80 10% dextrose/TPN
(5% dextrose if bwt B1500 g)
Day 2 100 Electrolyte solution/10%
dextrose/TPN
Day 3 120 Electrolyte solution/10%
dextrose/TPN
Day 4 140 Electrolyte solution/10%
dextrose/TPN
Day 5 150 Electrolyte solution/10%
dextrose/TPN Restricted fluidstwo-thirds of normal maintenance fluids.
Very low birth weight infants frequently require even higher initial rates of fluid administration and frequent reassessment of serum electrolytes, urine output, and body weight.
Fluid and electrolyte management 135
Increased fluid requirements may occur in the following circumstances:
= Low birth weight infants B1.5 kg. The very low birth weight infant has a very high insensible loss of fluid and thus increased requirements for free water.
= Phototherapy. Phototherapy increases insensible water loss by evaporation, thus fluid intake should be increased by 10 mL/kg per day per number of phototherapy unit light used in the infant1.5 kg and 20 mL/kg per day per number of lights used with birth weights B1.5 kg.37,38
= Radiant warmer. Nursing in a radiant warmer increases insensible fluid loss by a mean of 0.94 mL/kg per hour39 when compared with incubators. This increased water loss is not prevented by using a heat shield but may be prevented by using a plastic blanket.3941 Use of a humidified incubator is preferable, especially in preterm babies.
= Polyuric renal failure (especially in infantsB26 weeks’
gestation). Maintenance fluids will require very frequent readjustment, guided by regular monitoring of the weight and the serum electrolytes.
Maintenance fluid therapy may need to be decreased in the following circumstances:
= inappropriate ADH secretion;
= congestive heart failure;
= oliguric renal failure;
= patent ductus arteriosus.
Conservative patent ductus arteriosus (PDA) management involves fluid restriction to a total fluid intake of 120 mL/kg per day.42A high PDA closure rate (up to 100%) in preterm infants with PDA managed conservatively with fluid restric- tion (130 mL/kg per day), and adjustment of ventilation (reducing inspiration time and increasing the peak end expiratory pressure) may be achieved.43
In assessing the infant’s water requirements, one needs to evaluate weight change, urine output, specific gravity and osmolality, serum sodium and creatinine, and blood urea and osmolality. Normal urine output is 24 mL/kg per hour. In the first 24 hours of life, urinary output may be very low or even absent. During recovery from a severe illness associated with fluid retention or edema, polyuria may occur. A physiological diuresis (water loss) of up to 10% of body weight occurs over the first 45 days of life. This diuresis has the effect of decreasing total body water content by contracting the ECF volume. It is greater in the preterm infant whose total body water content is higher than that of the term infant. This water loss occurs despite usual fluid intakes and is typically accompanied by a negative sodium balance even when sodium is provided.
High fluid intake (170 mL/kg per day) increases the likelihood of symptomatic PDA.44 High fluid intake and/or high sodium intake may also increase the likelihood of respiratory complications both in the short term and in the longer term by increasing the frequency of chronic lung disease.45,46
Sodium regulation
Maintenance of normal serum sodium (135140 mmol/L) is principally controlled by the kidneys. The amount of sodium that can be excreted is limited by the GFR and the ability of the kidney to excrete a sodium load is diminished as compared with adults and falls progressively with decreasing gestational age.4749
Preterm infants have a higher fractional sodium excretion than full-term infants.47 Extrauterine existence accelerates tubular sodium reabsorption but not GFR, whose maturation is related to post-conceptual age. Al-Danhanet al. demon- strated that preterm infants B30 weeks’ gestation require a minimum of 5 mmol/kg per day of sodium and those of 3035 weeks’ gestation require 4 mmol/kg per day to achieve a positive sodium balance and maintain normal serum sodium.47,50
Intestinal absorption of sodium in the very preterm infant is low and improves progressively with increasing gestational age.48Neonates undergoing intensive care may gain signifi- cant amounts of fluid and sodium from drugs, bronchial lavage, and flushing of catheters, sources that are often overlooked. Hypernatremia may occur, especially in the very low birth weight infant, and may have adverse effects.51
Prenatal steroids induce maturation of renal tubular function. Infants who have been exposed to prenatal steroids have an earlier diuresis and natriuresis.30 Randomized controlled trials have shown that early sodium administra- tion increases the risks of hypernatremia, particularly if TEWL is high and water intake is limited, and increases the risks of respiratory morbidity by impeding the normal, physiological loss of extracellular fluid. Subsequently, once nutritional intake is sufficient to support growth, the extremely preterm infant is at risk of chronic sodium depletion. At this stage, an intake of at least 4 mmol/kg per day is required, or more particularly in the absence of antenatal steroid exposure.5256
Renal response to antidiuretic hormone
The human fetal pituitary secretes antidiuretic hormone (ADH) from 12 weeks’ gestation onwards. Labor and delivery are associated with a surge in ADH secretion in cord blood.
Both term and preterm infants are capable of an appropriate ADH response to stimuli. Although ADH levels in newborn infants are similar to adults, the antidiuretic response to ADH is blunted because a lower concentration gradient in the renal medulla lessens its effectiveness and low numbers of ADH receptors. Excess ADH can cause a drop in urine output and hyponatremia.57,58
Factors that result in excess or inappropriate secretion of antidiuretic hormone (SIADH) in the newborn include birth asphyxia, surgery, hypoxia, severe lung disease, positive pressure ventilation, intracranial hemorrhage, and pneu- mothorax. SIADH results in weight gain, hyponatremia, and oliguria. SIADH is diagnosed by documenting hypona- tremia in association with low serum osmolality and high or normal urine osmolality and high urinary sodium due to continued excretion of sodium in urine despite low serum 136 Fluid and electrolyte balance in the newborn
sodium. There is usually no evidence of fluid depletion. It is also important to note that the renal, adrenal, and thyroid functions are usually normal in SIADH. Management is by fluid restriction in addition to alleviating the primary cause.59
Sodium balance
Sodium is not required during the first 24 hours of life, during which time urine and sodium output are low. Sodium supplementation of 24 mmol/kg per day should be given when weight loss of approximately 510% of birth weight has occurred and postnatal diuresis has occurred.
Hyponatremia, defined as NaB130 mmol/L, may occur in the following circumstances:
= laboratory error;
= excess antidiuretic hormone secretion, where low urinary loss of water results in dilutional hyponatremia;
= large renal tubular losses of sodium as occurs in extreme prematurity or polyuric renal failure;
= congestive heart failure with dilutional hyponatremia;
= diuretic therapy with loss of sodium via the renal tubules;
= hypoadrenalism: congenital Addison’s disease, septic shock with adrenal failure, salt-wasting adrenogenital syndrome;
= maternal hyponatremia;60
= factitious hyponatremia as a result of hyperglycemia or hyperlipidemia;
= inadequate sodium intake in preterm infants with ex- cessive renal sodium loses;
= excessive large intakes of free water or electrolyte-free solutions like dextrose water.
Hypernatremia, serum sodium145 mmol/L, may occur in the following circumstances:
= laboratory error;
= high insensible water loss which is incompletely replaced;
= high urinary water losses which are not replaced;
= maternal hypernatremia;
= deficiency of antidiuretic hormone;
= rarely, excessive administration of Nain i.v. fluid flushes;
= excessive sodium bicarbonate administration in infants with metabolic acidosis.
Potassium balance
Potassium is predominantly an intracellular ion. No potas- sium is required on the first day of life. After this, intakes of 13 mmol/kg per day should replace losses and maintain a normal serum potassium of 3.55.8 mmol/L (Table 12.2).
Potassium should be cautiously administered in infants with renal dysfunction and the very low birth weight infant whose ability to excrete potassium may be limited. Early non- oliguric hyperkalemia may occur in 3050% of infants with birth weight B1 kg as a result of a potassium shift from intracellular to extracellular space. Hyperkalemia will be exaggerated by hypoxia, metabolic acidosis, catabolic stress,
and oliguria. The hyperkalemia may be severe enough to cause life-threatening arrhythmias.8,6164
Hyperkalemia, serum K6 mmol/L in a sample that is not hemolyzed, becomes concerning when6.5 mmol/L or if ECG changes occur. ECG changes in hyperkalemia vary from peaked T waves, as the earliest sign, to a widened QRS complex, bradycardia, tachycardia, supraventricular tachycar- dia (SVT), ventricular tachycardia, and ventricular fibrillation.
Hyperkalemia may occur in the following circumstances:
= laboratory error or hemolysis of blood sample;
= severe metabolic acidosis: with each 0.1 pH drop serum potassium increases by 0.6 mmol/L;
= tissue cell death with release of intracellular potassium, e.g. release of Kfrom neuronal cells and red blood cells (RBCs) post-intraventricular hemorrhage, trauma, or surgery;
= acute renal failure;
= very low birth weight in the absence of renal failure;
= very low birth weight in the absence of antenatal steroids;
= adrenal insufficiency secondary to acute adrenal failure as in sepsis/shock or congenital adrenal hyperplasia;
= severe hemolytic anemia.
MANAGEMENT OF HYPERKALEMIA
= Avoid potassium in all infusions in the first day of life.
= Infants born B28 weeks’ gestation should have serum potassium levels recorded from 12 to 48 hours of age. Blood gas analysis will identify the neonate with rising potassium levels. Laboratory measurement of serum potassium should be performed 12-hourly for the first 4872 hours of life.
= Only blood from umbilical arterial line, peripheral arterial line, arterial stab, or free flowing venous sample should be used.
= Treatment of hyperkalemia should be commenced if serum K]7 mmol/L confirmed on a non-hemolyzed arterial/venous sample and/or ECG changes are present and serum K57 mmol/L.
= ECG changes include tall peaked T waves, prolonged PR interval, small/absent P waves, widening of the QRS complex, asystole.
Treatments used in premature infants with non-oliguric hyperkalemia aim to decrease the arrhythmogenicity of hyperkalemia, redistribute potassium into the intracellular space, or remove potassium from the body65 (Fig. 12.2).
Sodium bicarbonate is not recommended. If acidosis is present, the underlying cause should be treated. Ion exchange resins are also not recommended. They have been shown to cause intestinal obstruction and perforation. Also, gastric masses found at autopsy were devoid of potassium, indicat- ing that no exchange had occurred.
CAUSES OF HYPOKALEMIA
Hypokalemia, serum potassiumB3.5 mmol/L, may occur in the following circumstances:
Fluid and electrolyte management 137
= laboratory error;
= alkalosis lowers serum potassium by shifting the potas- sium load intracellularly, but does not lower total body potassium;
= polyuric renal failure;
= gastrointestinal losses through vomiting or diarrhea or pooling of fluid in a ‘third space’, such as dilated loops with intestinal obstruction;
= diuretic therapy;
= inadequate intake;
= NG aspirate losses not replaced with appropriate fluids.
Hypokalemia predisposes to cardiac arrhythmias, paralytic ileus, urinary retention, and respiratory muscle paralysis.
Thus potassium balance must be carefully monitored, taking into account the influence that pH may have on the serum potassium, in that alkalosis shifts potassium which is predominantly an intracellular ion into the cells and acidosis has the reverse effect and that both hyper- and hypokalemia will have adverse effects.
Acid base balance
Normal values for pH are similar to those in the adult;
however PCO2and serum bicarbonate are both slightly lower in the newborn infant than in the adult.59,60The lungs and the kidney both have important roles in the maintenance of acidbase balance. The lung excretes volatile acid formed during metabolism as CO2. Respiratory failure will cause accumulation of CO2and respiratory acidosis.
METABOLIC ACIDOSIS
The normal kidney has a vital role in regulation of serum bicarbonate. In mature subjects serum bicarbonate is main- tained at approximately 25 mmol/L, but preterm infants have a lower threshold.66The kidney also has an important role in the excretion of non-volatile acid (mainly sulfur containing amino acids) produced by metabolism.
Causes of metabolic acidosis
= Perinatal asphyxia.
= Severe hypotension with impaired tissue perfusion.
= Acute renal failure.
= Acute diarrhea and dehydration.
= Excess ileal loss.
= Excess protein administration, e.g. excess amino acid in parenteral nutrition.
= Inborn errors of metabolism (e.g. organic acidemia).
= Sepsis.
Acute metabolic acidosis is common in the critically ill newborn. Treatment requires management of the underlying cause. Sodium bicarbonate may be used for severe acidosis by giving a dose of 12 mmol/kg of 4.2% sodium bicarbonate diluted in equal volume of water. There is currently no evidence from randomized control trials to support its routine use in neonatal resuscitation. Its effect on morbidity and mortality has not been well demonstrated. There is controversy about the value of i.v. sodium bicarbonate for correction of metabolic acidosis. It is no longer recom- mended for resuscitation in newborn infants and although it may correct acidosis in hypotensive shocked infants, this has not been shown to result in improvement in blood pressure or perfusion.67 Sodium bicarbonate infusion has potential side effects. Myocardial function may be depressed from the osmolar load with severe acidosis. Paradoxical intracellular acidosis may occur as well as a reduction in cerebral blood flow and increased risk of intraventricular hemorrhage. Use of sodium bicarbonate is therefore discouraged unless the infant has prolonged acidosis not responsive to other therapies including adequate ventilation.
Causes of metabolic alkalosis
Persistent vomiting causes hypochloremic alkalosis and body potassium depletion. This may occur with untreated pyloric stenosis or upper intestinal obstruction. Correction is by replacement of fluid, sodium chloride, and potas- sium. Rehydration and correction of depleted electrolytes will be followed by correction of the metabolic alkalosis.
Chronic respiratory acidosis, as in chronic lung disease (CLD), may cause renal re-regulation of sodium bicarbo- nate level at a higher threshold until pH is normal. Infants with chronic hypercapnia regularly have a serum bicarbo- nate of greater than 30 mmol/L. Permissive hypercapnia or controlled ventilation is a strategy adopted to limit the damage done by excessive mechanical ventilation pressures or volumes to the lungs in order to decrease the incidence of CLD.68
Hyperkalemia (serum K+≥6 mmol/L)
Serum K ≥6 mmol/L Without ECG changes
Monitor K+ 1–2 hourly using blood gas sample
i.v. 10% Calcium Gluconate 0.5–1 mL/kg i.v.
slowly over 5–10 minutes
Insulin/Dextrose infusion.
Start at 0.2 U insulin/kg per hour i.v. + 0.5g glucose/
kg per hour i.v.
Salbutamol infusion. 4 µg/kg i.v. over 10 minutes. May be repeated after 2 hours
Frusemide 1 mg/kg i.v.
Serum K+≥7 mmol/L OR ≤7 mmol/L with ECG changes
Figure 12.2 Management of hyperkalemia.
138 Fluid and electrolyte balance in the newborn
Glucose homeostasis
Glucose is the most important substrate for brain metabo- lism and whereas ketones, glycerol, and lactate can be used, a continuous supply of glucose is essential for normal neuro- logical function.69,70Fetal blood glucose is identical to that of maternal blood glucose since passive transfer of glucose occurs across the placenta.
HYPOGLYCEMIA
Immediately after delivery, blood glucose falls to2.5 mmol/L (45 mg/dL) in the term infant. Following delivery a combina- tion of hormonal responses (glucagon, growth hormone, thyroxine) and oral feeds, or in their absence i.v. fluids, serve to maintain blood glucose within a normal range. There is no consensus regarding the definition of hypoglycemia in the neonate.69,70 Blood glucose levels between 2.5 mmol/L (45 mg/dL) and 7.2 mmol/L (130 mg/dL) are accepted as being safe. Symptomatic hypoglycemia results in cyanosis, apnea, lethargy, seizures, or coma. Blood sugar values represent a continuum and there is no specific value at which brain damaging hypoglycemia will always occur.69,71However,, brain MRI after symptomatic neonatal hypoglycemia (median glucose level 1 mmol/L) without evidence of hypoxic-ischemic encephalopathy reveals white matter injury in 94% and neurodevelopmental impairment in 64% at 18 months.72
In the newborn infant requiring surgery, hypoglycemia is most commonly caused by vomiting or inadequate intake of fluids. Other contributing factors may include prematurity, septicemia, hypothermia, or hyperinsulinism as may occur in an infant of a diabetic mother. Infants with Beckwith Wiedemann syndrome who frequently may have omphalo- cele, commonly have elevated blood insulin levels and severe hypoglycemia.
Blood sugar in the infant at risk should be monitored at the bedside using a bedside screening glucose analyzer. Blood sugars below 22.5 mmol/L should be acted upon by giving a feed or giving a bolus of i.v. 10% dextrose as appropriate for the individual infant. Significant hypoglycemia should be confirmed by laboratory blood sugar before definitive action, such as i.v. glucose being given. This is because all screening methods are not completely accurate at low blood sugar levels.
HYPERGLYCEMIA
A blood glucose14 mmol/L (250 mg/dL) may cause a hyperosmolar state with glucosuria, osmotic dieresis, and dehydration. This elevated plasma osmolality increases the risk of intracranial hemorrhage, at least in the infant of less than 32 weeks’ gestation. Hyperglycemia most commonly occurs in the very low birth weight infant who is receiving large amounts of fluids to counteract insensible loss and whose ability to metabolize dextrose or glucose is limited.
Hyperglycemia may also be due to defective islet cell processing of proinsulin, insulin resistance, and non- suppression of endogenous glucose production during continuous exogenous glucose infusion.73,74 Infusion of
small doses of insulin may be required to counteract intractable hyperglycemia.73 Extreme low birth weight babies require a higher total dose of insulin for longer periods than low birth weight preterms. Exogenous insulin infusion partially reduces endogenous glucose production in preterm newborn infants. This treatment is efficient and safe when used with caution.73The use of insulin in preterm infants and prevention of hyperglycemia could also affect immune function, lipid metabolism, growth, and IGF-I generation leading to improved short-term clinical out- comes such as retinopathy of prematurity. It may also have longer-term health effects, however the outcomes of clinical trials are currently awaited.74
Calcium homeostasis
Calcium has a key role in many physiological processes, including activation and inhibition of enzymes, intracellular regulation of metabolic sequences, secretion and action of hormones, blood coagulation, muscle contraction, and nerve transmission. Ninety-nine percent of total body calcium is in bone, to which it gives structural support, with only about 1% in the ECF and soft tissues.75
Calcium is present in the extracellular fluid in three fractions: 3050% is bound to protein, principally albumin;
515% is complexed with citrate, lactate, bicarbonate, and inorganic ions; and 515% is ionized this is the metabolically active fraction of calcium. Calcium concentra- tion reported as mg/dL can be converted to molar units by dividing by four (e.g. 10 mg/dL converts to 2.5 mmol/
L).36,7678If serum albumin is low, total serum calcium falls, but the serum level of ionized calcium is unchanged. Serum calcium could be corrected for the level of serum albumin using the formula:
Corrected calcium(0.8[normal albumin neonatal albumin])serum Ca
Hydrogen ions compete with calcium for albumin binding sites. Thus acidosis increases serum ionized calcium levels without influencing total serum calcium levels. Prenatally, calcium is actively transported across the placenta from mother to fetus against a concentration gradient, which results in fetal hypercalcemia at the end of the last trimester and immediately after birth. Cord serum calcium in the full-term infant is approximately 2.75 mmol/L.77 In healthy full term infants calcium concentrations decrease for the first 2448 hours and reach a nadir of 1.82.1 mmol/L. Thereafter, calcium concentrations progressively rise to the mean values observed in older children. This transient drop in serum calcium is exaggerated in the preterm infant. Metabolic bone disease is a common feature, especially in extreme preterm infants less than 28 weeks’ gestation, and results from inadequate supply of nutrients (vitamin D, calcium, and phosphate), prolonged period of total parenteral nutrition, and prolonged period of immobilization. The main features which manifest between the 10th and 16th week of life include decreased Fluid and electrolyte management 139