Hypernatremia is a potentially serious condition in both term and preterm babies, which can lead to severe and permanent neurological damage. There are many physiological changes in sodium homeostasis that occur soon after birth. Understanding this physiological process, early anticipation of hypernatremia and familiarization with the neonatal management of hypernatremia can prevent mortality and long-term morbidity associated with this condition. This review aims to provide a practical and understandable approach to the diagnosis and management of hypernatremia in neonates.

Hypernatremia, defined as serum sodium of more than 145 mEq/L [1], is a common finding in preterm neonates in the neonatal intensive care unit (NICU) and in term infants after discharge from the hospital. Late recognition and delayed treatment lead to severe and prolonged hypernatremia with an increased risk of mortality and central nervous system morbidities like seizures, thrombosis, intracranial hemorrhage [2-4]. Extracerebral complications include acute kidney injury, transaminitis, hyperglycemia or hypoglycemia, metabolic acidosis, and disseminated intravascular coagulation [5]. Mortality and morbidity are related to hypernatremia itself [6] and inappropriate fluid management [4, 7-9].

The precise incidence of hypernatremia in newborns is difficult to ascertain because of variable incidence based on geographical location, limited accessibility to hospital data, and limited post-discharge follow-up data. However, the reported incidence in term newborns after discharge from the hospital varies from 1% [10] to 1.8% [11] to as high as 5.6% [12]. The main risk factors for hypernatremia in term newborns are related to early discharge from the hospital with ineffective lactation support or insufficient milk production leading to lactation failure [13-16].

In preterm infants, the reported incidence of hypernatremia is about 40% [17] and is usually due to insufficient fluid intake, excessive fluid loss, or excessive sodium intake [18]. Potential etiologies of hypernatremia in preterm and term neonates are summarized in Table 1.

Table 1.

Etiologies of hypernatremia in newborns

Etiologies of hypernatremia in newborns
Etiologies of hypernatremia in newborns

To better understand the pathophysiology of hypernatremia, it is essential to understand the normal physiology of sodium and water balance during the first few weeks after birth. This review will summarize newborn sodium homeostasis and describe the pathophysiology of hypernatremia and the clinical findings and management of neonates with hypernatremia. To simplify and guide the management of hypernatremia, we will use a classification of serum sodium levels as shown in Table 2 with some modifications [24].

Table 2.

Classification of hypernatremia

Classification of hypernatremia
Classification of hypernatremia

A normal serum sodium level ranges between 135 mEq/L and 145 mEq/L and is the principal cation of the extracellular fluid (ECF) further subdivided into plasma and interstitial fluid. Sodium is the main driving force for body water to move in and out of the cells and is monitored by multifactorial interactions between the heart, skin, kidney, and various hormones. The kidneys are the principal organ that controls sodium hemostasis. Most of the sodium filtered from the glomeruli is reabsorbed in proximal tubules, while the remaining amount is absorbed in various locations along the nephrons via a complex interplay between intrarenal hemodynamics, the renin-angiotensin system, vasopressin, antidiuretic hormone (ADH), and aldosterone [25]. By achieving sodium hemostasis, water balance is constantly maintained between the ECF and intracellular fluid (ICF) compartments.

During the transition from fetal to neonatal life, all newborns experience a one-time physiological drop in their ECF and ICF. In the first 4–7 days after birth, term newborns typically have a decrease of up to 10% [26] of their birth weight, while preterm neonates have a decrease of up to 15% [26, 27], which is regained 10–14 days after birth [28]. This physiological transition should still occur for newborns who initially require intravenous (IV) fluids. This physiological drop must be facilitated in various disease processes, failure of which can lead to long-term morbidities [29-31].

After birth, term newborns can reabsorb the filtered sodium relatively well through their kidneys. In contrast, preterm infants have immature kidneys with blunted end-organ responsiveness to various hormones [26, 32]. Therefore, sodium loss in preterm infants is directly related to the degree of prematurity [33]. Thus, special attention must occur when managing fluids and electrolytes in extremely preterm newborns to prevent hypernatremia. This will be discussed in more detail later in this review.

It is important to mention that “hypernatremic dehydration” is not a diagnosis but a sign of underlying illness related to many diverse pathological and physiological processes. While hypernatremia in neonates can result from increased serum sodium levels, most commonly, it is caused by excess water loss or insufficient water intake, or a combination of both. These processes result in a net loss of water (from ECF) without an accompanying fall in serum sodium level, leading to a hypertonic intravascular state with its associated effects and complications.

In a normal state, the ECF and ICF remain in balance with no net movement of water in either direction. If there is an increase in the amount of sodium in the ECF, there will be an associated increase in the tonicity of the ECF (mainly plasma), resulting in a hypertonic state. This hypertonic state of the ECF causes net movement of water from ICF toward ECF due to osmotic gradient and continues until osmolarity is balanced across both sides of the cell membrane. This leads to a decrease in the ICF volume, causing cells to shrink and distort their shapes. If the sodium increases further or is unrecognized over several days to weeks, the cells start regulating their intracellular volume by several adaptive mechanisms present in all body tissues to maintain the balance between ECF and ICF; these mechanisms maintain plasma tonicity by producing intrinsically small solutes called osmolytes [34, 35].

The physiological adaptations in cerebral tissues are slow and usually take about a week to preserve about 98% of their water content [36]. This adaptation limits water egression from the brain cells, maintains an average brain cell volume, and stabilizes intracellular protein during this hyperosmolar state [36-39]. This cerebral adaptive mechanism may not be sufficient in acute hypernatremia, and egressing water from brain cells distorts their architecture and induces structural changes [36]. Cell shrinkage causes separation of the brain from meningeal layers, leading to rupture of bridging veins with resultant intracerebral hemorrhages [40], venous sinus thrombosis, and infarction [41].

Rapid correction of hypernatremia returns the cell volume of all body cells except those in the brain. In the brain, rapid sodium level correction results in cerebral edema because of persistent and incomplete metabolism of osmolytes in neuron and glial tissues [42]. All these changes are shown schematically in Figure 1.

Fig. 1.

Schematic representation of the effect of hyper- and hypo-osmolality of ECF and ICF compartments. a Under normal conditions, water freely moves between ICF and ECF (IF and plasma). b If plasma fluid becomes hypotonic due to hypotonic fluids administered rapidly in the setting of chronic hypernatremia, water moves towards ICF due to the presence of osmolytes, causing cellular swelling and cerebral edema, clinically manifesting as encephalopathy and cerebral pontine Myelinosis. c Hypertonic plasma attracts more water from the ICF causing cellular distortion and shrinkage, resulting in intracerebral bleed, which clinically manifests as seizures and irritability.

Fig. 1.

Schematic representation of the effect of hyper- and hypo-osmolality of ECF and ICF compartments. a Under normal conditions, water freely moves between ICF and ECF (IF and plasma). b If plasma fluid becomes hypotonic due to hypotonic fluids administered rapidly in the setting of chronic hypernatremia, water moves towards ICF due to the presence of osmolytes, causing cellular swelling and cerebral edema, clinically manifesting as encephalopathy and cerebral pontine Myelinosis. c Hypertonic plasma attracts more water from the ICF causing cellular distortion and shrinkage, resulting in intracerebral bleed, which clinically manifests as seizures and irritability.

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Awareness and understanding of these physiological adaptations during acute and chronic hypernatremia is critical during the treatment of hypernatremic dehydration to prevent complications. Rapid fluid administration or administration of a large amount of hypotonic fluid can cause significant changes in ECF osmolality and a shift in the water toward ICF, eventually leading to cerebral edema and possible irreversible cell damage.

The clinical signs and symptoms of hypernatremic dehydration are quite variable and may appear very late. For newborns who have been discharged, pediatric clinicians should have increased vigilance for this condition and take a medical history focused on lactation frequency and techniques, formula preparation techniques, maternal health, number of wet diapers, stooling frequency, fever, excessive swaddling, and perspiration [8].

Discharged term newborns with hypernatremia usually present within 7–10 days with more than 10% weight loss, severe indirect hyperbilirubinemia approaching exchange level, irritability, and voracious hunger and thirst. Other neonates may present with lethargy with signs of dehydration, tachycardia, hypotension, fever, and metabolic acidosis, signifying moderate to severe intravascular fluid loss. In severe cases, neurological symptoms may progress from irritability, a high-pitched cry, weakness, twitching, seizures, encephalopathy, and even death.

In extremely low birth weight (ELBW) infants in the NICU, clues of hypernatremic dehydration are excessive weight loss and negative fluid balance. Hypernatremia is sometimes detected in this population by routine blood tests rather than any specific clinical signs or symptoms. Investigations necessary in babies with hypernatremia are summarized in Table 3.

Table 3.

Investigations

Investigations
Investigations

The principles of hypernatremic management in newborns include the following:

1.Identifying and treating the underlying cause

2.Correcting the underlying fluid deficit

3.Ensuring that there is enough free water to safely lower serum sodium towards normal value

4.Continuing maintenance fluid

Early recognition and management improve the outcome of neonates with hypernatremia. If a term newborn in the emergency department or a preterm infant in the NICU has an elevated serum sodium, the aim of the management is to slowly normalize the serum sodium level by giving a sufficient amount of free water. Patients with sodium overload or a renal concentrating defect require more hypotonic fluid than those with volume-depleted states and an intact renal concentrating ability [43, 44].

There are currently no randomized controlled trials or standardized validated guidelines about the use of enteral versus parenteral fluids for the management of neonates with hypernatremia [45, 46]. Available evidence varies between the desired decline in serum sodium concentration [8, 47, 48] and the optimal sodium concentration of the rehydrating fluid used [8, 47-50]. Different calculations and formulas to correct hypernatremia in neonates that are discussed in the literature have different free water calculations; however, their principle remains the same: to avoid a rapid decline in serum sodium concentration. To better understand the physiology of hypernatremic treatment, it is essential to have a basic understanding of the plasma or ECF tonicity and the type of parenteral fluids used for treatment.

Regulation of Body Tonicity

Although tonicity and osmolality are comparable, there is a slight difference between them. Tonicity refers to the osmotic pressure across two solutions separated by semipermeable membrane and measures solutes/effective osmoles that do not freely cross the membrane and are different for ICF and ECF compartments. Hence, body tonicity includes both ICF and ECF tonicity. On the other hand, osmolality refers to the total concentration of penetrating and nonpenetrating solutes [51]. Sodium and glucose are the primary solutes to maintain ECF tonicity and osmolality. In contrast, blood urea is permeable to membranes and contributes to osmolality but not body tonicity. As an intracellular cation, potassium only contributes to ICF tonicity.

All the cells in the body (except in distal nephron cells) have the same concentrations of solutes and water that pass freely across cell membranes. Therefore, the accumulation of osmoles in the ECF and ICF compartments affects the driving force of water to move in the direction of higher solute concentration to maintain plasma tonicity. Hence, the hypotonic plasma causes water to move toward the ICF compartment, resulting in cellular edema; conversely, hypertonic plasma creates cellular shrinkage.

To calculate plasma osmolality and tonicity, the following formulas are used: [51]

Plasma osmolality (mOsm/kg water): [2 × (Na) (mEq/L)] + BUN (mg/dL)/2.8 + glucose (mg/dL)/18

Plasma tonicity (mOsm/kg water): total plasma osmolality (mOsm/kg water) − BUN (mg/dL)/2.8 OR [2 × (Na) (mEq/L)] + glucose (mg/dL)/18

Except for dextrose water, any parenteral fluid that is used for rehydration has an isotonic and free water component, as shown in Table 4. While remaining within the ECF, the isotonic part of the parenteral fluid does not affect tonicity and cell volume; however, the free water component distributes freely between ECF and ICF compartments, affecting tonicity. Therefore, the free and isotonic parts of any fluid administered to a neonate for rehydration must be known. Giving too much free water will decrease the ECF tonicity more rapidly than the recommended decrease of 2 mOsm/kg/h or 0.5–1 mEq/L/h [51]. In contrast, free water administration will cause the ICF tonicity, particularly in brain cells, to remain high despite a fall in ECF tonicity for an extended period, thereby causing a fluid shift to the ICF and causing cerebral edema with its associated complications mentioned above. For example, if serum sodium in ECF is 154 mEq/L and 0.9% sodium chloride is administered intravenously, there will be no net movement of water across the cell membrane; however, if the neonate is given 0.45% saline intravenously, then 50% of fluid will be permeable across the membrane; hence, this portion is called free water and the remaining 50% will be isotonic and remain on one side of the membrane, allowing it to be osmotically active. Thus, the free and isotonic contents of fluids can be calculated based on their sodium contents, as shown in Table 4, which is further explained later in the review. In the next section, fluid management will be explained separately for neonates with anuria and a shock-like state and those with observed diuresis and hemodynamically stable.

Table 4.

FW and isotonic component as volume percent at various serum sodium levels

FW and isotonic component as volume percent at various serum sodium levels
FW and isotonic component as volume percent at various serum sodium levels

Hypernatremia in Term Neonate with Anuria and Hemodynamic Instability

Emergency Treatment. In term neonates who have moderate to severe hypernatremia with anuria and hemodynamic instability, the priority is to restore the neonate’s fluid volume status and cardiovascular stability. Affected patients should receive 10–20 mL/kg of normal saline (NS, 0.9%) over 30 min as an initial fluid resuscitation before correcting the free water deficit [52]. A second saline bolus can be given, if required, to maintain a normal hemodynamic status. Providing a second NS bolus might dilute the serum sodium rapidly, subsequently causing cerebral edema; therefore, simultaneous running of 3% saline can assist in preventing such acute drop in serum sodium level [53]. It is challenging to recognize which neonate is best suited for this regime in clinical practice.

With any lactating neonate who presents in the emergency department with more than 10% weight loss from birth with severe dehydration, suspect extreme hypernatremia [50], and above strategy can be adopted for second saline bolus as soon as laboratory values are available. Once the amount of 3% saline to be added to 1 L of NS (explained later below) is calculated, the amount required to be added to bolus fluid can be easily calculated by [53].

Amount of Na added to bolus fluid: milliliter of 3% saline per liter of NS × amount of NS bolus (mL)/1,000 mL.

Ongoing Treatment and Previous Water Deficit/Calculating Free Water Deficit. Once an infant is stabilized, the next stage is the rehydration phase in which the insensible water losses and the fluid deficit are calculated. The infusion rate is then determined by the number of days required to steadily decrease the serum sodium level. Daily maintenance fluids and previous water deficit are calculated every 24 h in this phase.

Maintenance Fluids. Routine parenteral maintenance for a healthy term neonate is calculated based on daily insensible water losses (30–40 mL/kg), urine output (50–60 mL/kg), and stool (0–10 mL/kg) corresponding to the daily requirement of about 100 mL/kg/day [8]. Because the neonate in this section is anuric on presentation, only insensible fluid loss (40 mL/kg) will be calculated as maintenance requirements, with an additional 20 mL/kg if the neonate is under a radiant warmer.

Although insensible water loss is electrolyte-free, urinary water losses or loose stools contain electrolytes, which reflect ECF volume status, renal tubular function, and intact antidiuretic hormones. As a result of hyperosmolality and hypovolemia, the ADH levels remain high in a neonate with severe dehydration, leading to oliguria until the tonicity of the ECF and the serum sodium are steadily restored to normal. In extreme cases, pre-renal acute kidney injury may occur with a rising serum creatinine level associated with renal parenchymal injury or vascular thrombosis [54]. Therefore, careful monitoring of the neonate’s urine output, clinical findings, and serum sodium levels are critical in such newborns. In contrast, if the baby continues to pass dilute urine in the presence of hypernatremia, an abnormality with the ADH pathway of central or nephrogenic origin should be considered [8].

The maintenance fluids can be determined by adding maintenance sodium to dextrose, maintaining a glucose infusion rate (GIR) of at least 5 mg/kg/min, and sterile water. Alternatively, a premixed dextrose saline solution of 0.2%, 0.45%, or 0.9% can be used based on serum sodium values, as shown in Figure 2.

Fig. 2.

Schematic representation for IV fluid management according to serum sodium levels and timings for blood tests frequency.

Fig. 2.

Schematic representation for IV fluid management according to serum sodium levels and timings for blood tests frequency.

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Free Water Deficit. Free water deficit is the amount of water free of solutes, which dilutes the sodium back to normal when added to the body [55]. The amount depends on the initial serum sodium level and the desired decrease in serum sodium level for that day. Free water distributes freely throughout total body water, and total body water represents 70% of body weight (70 mL/kg) for newborns and 60% of body weight (60 mL/kg) for children over 1 year [8] as shown in Table 5.

Table 5.

FW calculation in moderate and extreme hypernatremia for infants and newborns to drop serum Na level by 1 mEq/L

FW calculation in moderate and extreme hypernatremia for infants and newborns to drop serum Na level by 1 mEq/L
FW calculation in moderate and extreme hypernatremia for infants and newborns to drop serum Na level by 1 mEq/L

The amount of free water required to decrease Na safely is calculated using the following formula:

(Actual Na – Desired Na/150) × 1,000 × percentage of total body water × weight in kg.

The difference between actual and desired sodium should not be more than 12 mEq/day. Generally, in a healthy term infant, to reduce the serum sodium level by 1 mEq/L/h, 4.5 mL/kg of free water is required [8]. This is true when the infant has a serum sodium level up to 180 mEq/L. In extreme hypernatremia, with a serum sodium level >180 mEq/L, to reduce the Na by 1 mEq/L/h, 3.5 mL/kg of free water is necessary [8]. The safe threshold of serum sodium to be lowered per hour is 0.5 mEq/L, and hence in 24 h, a maximum drop of sodium allowed is 12 mEq/L [52, 56]; therefore, the amount of free water required for mild–severe hypernatremia would be 4.5 mL/kg × 12 mEq/L = 54 mL/kg free water per day. In case of extreme hypernatremia, to decrease the sodium by 12 mEq/L, the amount of free water required would be 3.5 mL/kg × 12 mEq/L = 42 mL/kg free water per day.

Calculating Previous Deficit. It is challenging to assess how much water in term newborns is lost from their total body water to calculate the previous fluid deficit. This calculation is particularly difficult because term newborns may physiologically decrease their birth weight by 10% during the first week after birth. The previous fluid deficit is roughly the difference between the neonate’s birth and current weight. For example, if a neonate has a current weight of 2,500 g and had a birth weight of 3,000 g, the fluid deficit would be 3000 – 2500 = 500 g. With this 500 g weight loss, 500 mL is assumed to be the previous fluid deficit.

The previous fluid deficit is then divided over the number of days required to normalize the infant’s serum sodium. For example, if serum sodium is 170 mEq/L, 48 h is required to dilute serum sodium to 146 mEq/L; therefore, a free water deficit is allocated to be delivered over 48 h.

Total Amount of Fluids. After calculating 24-h maintenance fluid (only insensible water loss in this case) and the previous fluid deficit, to determine the total amount of fluids, subtract any fluid boluses that were given and provide the remaining volume via 1 or 2 peripheral IV lines to easily titrate fluids based on the desired versus actual fall in sodium levels.

Type of Fluids. There is no consensus about optimum sodium concentration of fluid for a safe decline in serum sodium in hypernatremia [57, 58]; however, for practical reasons, the type of fluids required mainly depends on the initial serum Na level. To determine the type of fluids required for free water replacement, one should be familiar with the amount of free water in commercially available fluids as shown in Table 4, and calculations should be based on individual serum sodium levels: Percentage free water in IV fluids = 1 – (IV fluid sodium/serum sodium).

In mild hypernatremia cases, either 5–10% dextrose water (keeping GIR at least 4 mg/kg/min) alone or in combination with 0.2% saline (31 mEq/L of sodium) is the usual starting fluid [59]. In contrast, for moderate to severe hypernatremia, 0.45% dextrose (D5) saline (77 mEq/L of sodium) and 0.9% dextrose (D5) saline (154 mEq/L sodium) is recommended [50]. We suggest starting both fluids simultaneously, with the initial starting rate depending on the serum sodium level; thus, in moderate hypernatremia, about 2/3 of the fluids should be from 0.45% dextrose (D5) saline and 1/3 from 0.9% dextrose (D5) saline while in severe hypernatremia, 2/3 of the fluids should be from 0.9% dextrose (D5) saline and 1/3 from 0.45% dextrose (D5) saline.

Serum sodium levels should be monitored every 2–4 h for an initial 12 h or longer, and the rate of fluids is titrated till the desired decline is accomplished. For example, if the drop in sodium level is more than the desired value (0.5 mEq/h), then there should be a decrease in the rate of 0.45% dextrose (D5) saline and an increase in the rate of 0.9% dextrose (D5) saline (by 20 mL/kg). On the other hand, if the desired drop in serum sodium level is less than 0.5 mEq/h, there should be an increase in the rate of 0.45% dextrose (D5) saline and a decrease in the rate of 0.9% dextrose (D5) saline (by 20 mL/kg). There is no scientific basis for this regime; however, it provides the most practical and straightforward way to titrate sodium decrease to prevent cerebral edema.

Fluid management in extreme hypernatremia (sodium >180 mEq/L) is more complex and not straightforward. Reports in the literature recommend that clinicians prepare a special solution for this purpose by adding various quantities of 3% sodium chloride (0.514 mEq Na/mL) per liter of 0.9% saline to raise the sodium content of a solution to about 10–15 mEq less than the patient’s serum sodium [60]. However, calculations and preparation of such a solution within the desired time frame are complex and sometimes may not even be possible in some units, particularly in low middle-income countries where the incidence of such conditions is higher [61, 62]. Therefore, if the serum sodium level is in the extreme category, particularly >190 mEq/L, a pediatric nephrologist should be consulted to discuss the possibility of peritoneal dialysis [11]. In the meantime, if no facilities are available for preparing the special solution, start parenteral rehydration therapy with only (0.9%) dextrose (D5) containing 154 mEq/L sodium and keep monitoring serum sodium level closely till a desired decline of sodium is achieved. If the expected sodium decline is >0.5 mEq/h, the rate of parenteral fluid (by 20%) should be reduced every 2 h until the desired decline is achieved. Rehydration fluid for values between 180 and 190 mEq/L can be cautiously started with the regime of severe hypernatremia with frequent electrolytes monitoring every 2 h, as mentioned above.

The frequency of serum electrolytes monitoring and relevant fluids used for management at various serum sodium levels are schematically represented in Figure 2. For units that can easily prepare a special solution, the equation to calculate the amount of 3% saline to be added to NS [50] is as follows: [1000 × (desired Na – 154)]/(500 – desired Na) = mL of 3% saline added to 1 L of NS. As mentioned above, the desired decline in sodium should not exceed >12 mEq/day.

Ongoing Replacement. Once urine output is observed and measured, replace this urinary volume plus any ongoing fluid losses milliliter by milliliter with 0.2% or 0.45% saline, depending on urine electrolyte results. The idea is to replace it with hypotonic fluid. Once urinary electrolytes are known, and urine output is >1 mL/kg/h, add potassium in the replacement fluids.

Duration of Treatment. The total duration of parenteral fluids depends on the initial serum sodium level. Fluid calculations are done every day as mentioned in the steps above and given over 24 h until the serum sodium level is <150 mEq/L. The number of days required to correct serum sodium is the difference between the current serum sodium level and 145 divided by 15 (serum Na–145/15) [60]. In moderate to severe hypernatremia, 1–2 days for correction are usually sufficient, but in extreme cases (>180 mEq/L), 3–4 days are typically required to normalize sodium level [8].

Monitoring of Sodium Level and Follow-Up. Serum electrolytes, glucose, BUN, and creatinine should be monitored every 4–6 h in neonates with moderate hypernatremia, while every 2 h in severe to extreme sodium values until the desired drop in sodium level is accomplished. Once the serum Na level reaches <150 mEq/L, the frequency of monitoring can be modified. Vital signs, including blood pressure, strict monitoring of intake output, and periodic weight check, should be closely viewed.

Ongoing Management and Monitoring

a.Affected infants often have associated fever that is most likely related to the degree of dehydration; however, they should be on the appropriate antibiotics till an infection is ruled out.

b.Hyperglycemia is usually associated with hypernatremia [63] and should not be treated with insulin in term newborns to avoid an abrupt fall in plasma tonicity [64]. The hyperglycemia simultaneously improves with rehydration.

c.Metabolic acidosis usually accompanies hypernatremia for a variable period and should not be treated with bicarbonate as it is self-corrected gradually with rehydration.

d.In case of seizures, the serum sodium should be acutely increased. In this instance, 3% saline should be administered at 4–6 mL/kg to provide the least amount of free water [60]. Generally, 1 mL/kg of 3% saline increases sodium by 1 mEq/L [50].

Enteral versus Parenteral Treatment. There are currently no standard guidelines as to which neonates require enteral or parenteral rehydration therapy. Harding et al. [15] recommend oral rehydration with human milk or substitute if there is no hemodynamic instability. Benshalom et al. [65] also utilized the enteral route after approximately 10 h of parenteral rehydration therapy with a median sodium level of 156 mEq/L. López Candiani [66] recommends that in all newborns with serum sodium levels lower than 160 mEq/L and having no contraindication for oral intake, the enteral route is preferred, and in all other cases, a parenteral route with appropriate sodium-containing fluids.

Erdemir et al. [67] compared enteral versus parenteral rehydration in their review and found a significant decline in sodium level between the two groups at 12 and 24 h, with a parenteral group having more nonsafe reductions than the oral rehydration group. However, no long-term neurodevelopmental follow-up evaluation was reported.

We recommend that once parenteral rehydration is done and the patient is hemodynamically stable, slow introduction of human or formula milk can be instituted, and IV fluids decreased accordingly once serum sodium is <150 mEq/L. Human milk is preferred, and if not, an available similar substitute can be given. It is essential to mention that the enteral use of sterile water is not recommended due to its association with enterocolitis and intestinal perforation in ELBW babies with hypernatremia [68, 69].

Hypernatremia in Babies with Observed Urine Output and Hemodynamic Stability

In a newborn with hypernatremia who is hemodynamically stable with observed ongoing diuresis, the management plan will be the same as mentioned above for an anuric neonate. Thus, the free water and the previous fluid deficit will be calculated in the same way as mentioned for an anuric neonate with unstable blood pressure without fluid boluses. However, the following exceptions will be present:

1.There is a difference in the calculation of fluid maintenance as both insensible and sensible fluid losses need to be considered. If the presentation is after 7 days of age, daily maintenance fluid will be at 150 mL/kg/day, and if <7 days, then depending on the day of presentation, fluids will be calculated assuming at birth fluids to be 60 mL/kg/day and each day 20 mL/kg increment, until a daily maintenance of 150 mL/kg/day is reached.

2.Insensible water needs to be considered 50–60 mL/kg/day if a neonate is nursed under a radiant warmer instead of the usual 30–40 mL/kg/day.

Clinical Scenarios to Understand the Concepts of Fluid Calculations

Example 1. Let’s calculate fluids for a newborn baby born at term gestational age with a birth weight of 3,000 g, having 20% weight loss with sodium of 165 mEq/L. This infant is anuric and hemodynamically unstable, and the current weight checked is 2,400 g.

1.Initial bolus of NS (0.9%) 10 mL/kg = 30 mL (as per“Emergency treatment” explained above).

2.Maintenance fluids (only insensible water needs) = 40 mL/kg = 120 mL/24 h (use 60 mL/kg if baby is under radiant warmer).

3.Free water deficit = 4.5 × 12 × 3 = 162 mL + 108 mL for further 8 mEq/12 h drop. Hence, total free water for 36 h = 270 mL (as per “calculating free water deficit”).

4.Previous fluid deficit = 3,000 – 2,400 = 600 mL (as per “previous fluid deficit calculation” explained above).

5.Subtract initial fluid bolus from previous fluid deficit = 600–30 = 570 mL.

6.Number of days required for sodium correction = 165 −145/15 = 1.5 days (36 h).

7.570 mL to be given over 1.5 days.

8.Total fluids for 36 h (maintenance + previous deficit) = 120 + 60 + 570 mL = 750 mL = 20.8 mL/h for 36 h will be expected to decline serum sodium from 165 mEq/L to 145 mEq/L over 36 h.

9.Type of fluid will be 0.45% dextrose (D5) saline (75%) + 0.9% dextrose (D5) saline (25%) via two peripheral IV lines and rate titrated to achieve the desired fall in sodium level by close monitoring.

Once the urine output is observed and measured, it is replaced by hypotonic fluid, i.e., 0.2–0.45% saline, milliliter for milliliter, depending on urine electrolytes, and consider adding potassium chloride in replacement fluids.

Example 2. Let’s calculate fluids for a newborn born at term gestational age with a birth weight of 3,000 g, having 20% weight loss with sodium of 182 mEq/L. The infant is anuric and hemodynamically unstable, and the current weight checked is 2,400 g.

1.NS bolus (0.9%) 10 mL/kg = 30 mL (as per “Emergency treatment” explained above). Ideally, if any further bolus is required, it should be a special solution; however, slow NS at the same amount can be given to maintain cardiovascular stability.

2.Maintenance fluids (only insensible water needs) = 40 mL/kg = 120 mL/24 h.

3.Free water deficit = 3.5 × 12 × 3 = 126 mL × 3 days = 378 mL (as per “calculating free water deficit” explained above).

4.Previous deficit = 3,000–2,400 = 600 mL (as per “previous fluid deficit calculation”).

5.Subtract initial bolus from previous fluid deficit = 600–30 = 570 mL.

6.570 mL to be given over 3 days.

7.Total fluids for 72 h (maintenance + previous deficit) = (120 × 3) + 570 = 930 mL = 13 mL/h for 72 h.

8.Type of fluid: 0.45% dextrose (D5) saline (25%) + 0.9% dextrose (D5) saline (75%) via two peripheral IV lines and rate titrated to achieve the desired fall in sodium level by close monitoring.

Once the urine output is observed and measured, it is replaced milliliters for milliliters by hypotonic fluid, i.e., 0.2–0.45% saline, depending on urine electrolytes, and also consider adding potassium chloride in replacement fluids.

Management of Hypernatremia in Special Situations

ELBW Babies

The high serum sodium level ELBW is most likely due to trans-epidermal water loss [68, 69] (usually around 2/3rd, while the remaining 1/3rd is lost via respiratory tract) [70, 71] and polyuria leading to ECF contraction. Usually, it occurs after 24–48 h after birth, corresponding to the diuretic phase as respiratory distress syndrome improves. Clinical clues to this phase include weight loss, high serum sodium, BUN, and creatinine levels.

Such neonates usually receive maintenance sodium in total parenteral nutrition (TPN), while sodium is also being administered in arterial line infusions, medications, and IV saline push to keep peripheral IV line open; however, the serum sodium is unlikely to be due to an increased intake of sodium, a common misconception among neonatologists.

The following are the salient features to address hypernatremia in ELBW neonates:

1.Place infants in the humidified incubator and target humidity up to 95%.

2.In the initial oliguric phase, starter parenteral nutrition (PN) with an electrolyte-free solution should be provided.

3.Once the diuretic phase is established with urine output of >3 mL/kg/h and weight loss of about 5% [70], start lipids and the starter PN should be replaced with a regular maintenance sodium intake at 3–4 mEq/kg/day [72] and potassium 1–2 mEq/kg/day. Usually, electrolytes are given as acetate to counteract associated metabolic acidosis and hyperchloremia.

4.Besides PN as maintenance, it is worthwhile to run about 0.5 mL/h of Dextrose 5% as a side drip and titrate closely based on 4–6 h urine output. In this way, PN with acetate runs at a constant rate, while adjustments in any electrolyte disturbance or hyperglycemia are attempted with the rate of side drip fluids. This is important as fluids, electrolytes, and glucose status change frequently in the first 72 h of age in these ELBW neonates and should be monitored every 8–12 h or more depending on the clinical status.

5.Fluids can be increased at times in increments of about 10–20 mL/kg, considering ongoing polyuria intake/output as a guide. If associated with hyperglycemia, dextrose water be tailored accordingly to keep (GIR) at least 4 mg/kg/min at minimum.

6.If hyperglycemia persists, despite the GIR to 4 mg/kg/min from all sources, insulin therapy should be started to prevent osmotic diuresis [73], further adding to already polyuria.

7.Since hypernatremia in these preterm babies develops quickly under controlled settings in the NICU, rapid correction of this type is relatively safe as idiogenic osmoles are not developed that quickly intracellularly; hence, cerebral edema is unlikely [26] to occur.

8.Avoid giving repeated sodium bicarbonate boluses to treat metabolic acidosis; instead, treat slowly with PN containing acetate.

Example

Let us calculate the fluid needed for an ELBW infant weighing 600 g at birth during the first 5 days after birth, as shown in Figure 3.

Fig. 3.

Serum sodium level in the first 5 days and other useful parameters for monitoring in ELBW babies (see text for explanation).

Fig. 3.

Serum sodium level in the first 5 days and other useful parameters for monitoring in ELBW babies (see text for explanation).

Close modal

The fluid calculation is challenging, and treatment of hypernatremia in such neonates requires consideration of many factors such as fluid balance, amount and type of ongoing fluids with their sodium content, hyperglycemia, and environmental humidity.

As shown in Figure 3, serial sodium levels slowly increase from about 12 h of age from 140 mEq/L to a maximum of about 158 mEq/L, corresponding to polyuria with negative fluid balance and hyperglycemia, which cause osmotic diuresis further complicating the ongoing polyuria. As the sodium level increases, fluid intake also increases by about 20–30 mL/kg/day. The fluid type changes according to serum sodium level and blood sugars, which needs close monitoring every 6–12 h. The kind of fluids used and tailored during this period is essential, and practice varies widely among various units with plain dextrose water 5% (D5W) to 0.45% saline or simple sterile water to ensure sodium intake remains at normal daily requirements.

In this example, starter PN started at 60 mL/kg/day from day 0 and changed to routine TPN and lipids after 24 h of age at 80 mL/kg/day to 100 mL/kg/day at 48 h of age onward to provide a constant nutritional needs and with maximum acetate given as sodium/potassium acetate to counteract associated metabolic acidosis. D5W running at 0.5 mL/h (corresponding to about 20 mL/kg/day) through the second lumen of an umbilical venous catheter can be increased in increments of 20–30 mL/kg/day as shown in Figure 3 for fluid adjustments depending on fluid balance, sodium, and blood glucose level every 6 h and changed accordingly, keeping the total PN rate at constant to provide a steady GIR of about 4.3 mg/kg/min, the standard basal requirement for the brain. Insulin needs to be started and adjusted according to the sliding scale (Table 6) as blood sugar rises above 10 mmol/L without glycosuria.

Table 6.

Sliding scale insulin [74]

Sliding scale insulin [74]
Sliding scale insulin [74]

If heparin saline in 0.45% saline is used for arterial line fluid at 0.5 mL/h, it provides about 1.5 mEq/L of sodium intake, which increases to about 2.5 mEq/L when sodium acetate is provided in TPN in a baby weighing 600 g.

In addition to fluid provision, humidity in the incubator is adjusted up to 95% to minimize transepidermal fluid loss and tailored to unit guidelines for about a week. Daily weight needs to be done to aid in fluid adjustments.

Hypernatremia and Lactation in Term Neonates

A special mention about hypernatremia associated with lactation is necessary since most of the cases are prevalent in infants born to first-time mothers [75], with an uneventful delivery and discharged earlier than 48 h from the hospital before establishing adequate successful lactation. To understand this scenario better, we need to know the newborn’s average milk intake and composition on the first day, which changes per day after delivery. On the first postpartum day, usually, infants take a volume of less than 100 mL/day of human milk, and subsequently, after day 2, as the milk production increases, intake also improves [76, 77]. During the same period, milk contents, including sodium and chloride, dramatically change with a fall in sodium and an increase in lactose contents [77]. Average sodium content in human milk varies with the day, with values ranging from 65 to 70 mEq/L in early colostrum to about 7–10 mEq/L in mature milk, usually 2 weeks after delivery [78, 79].

Sometimes despite adequate milk supply, infants may have ineffective or infrequent sucking, likely due to factors [80] related to maternal stress, fatigue, illness, mastitis [81], or infant conditions like cleft lip and palate, trisomy 21, etc. All these factors fail normal physiological adaptation to postnatal milk production and its contents. A fall in human milk sodium content predicts successful lactation [82], and persistent elevation signifies impaired lactogenesis [83].

As the infant demand for milk supply is not met, average physiological weight loss is exaggerated due to suboptimal calories, water intake, and catabolism of fat stores and muscle protein. These infants typically present within 1–3 weeks of discharge from the hospital with signs and symptoms of severe hypernatremic dehydration. Peters’ [84] described these infants’ clinical features and their mothers in their review. It is, therefore, vital to estimate human milk sodium content in an exclusively breastfed newborn presenting with hypernatremia in addition to other laboratory investigations.

To prevent such a situation, counseling, adequate lactation support, and education to mothers with limited experience in infants’ upbringing are essential. Infants with greater than 7% weight loss should be evaluated for feeding problems, and aggressive lactation support is provided [85]. Close follow-up of any baby discharged within 3–5 days [86] of life, i.e., within 48–72 h from the hospital, is important for a weight check to identify vulnerable infants and institute early therapy to prevent long-term morbidities of hypernatremia.

Diagnosis and management of hypernatremia in newborns require high vigilance and education. In all infants cared for in NICU, careful monitoring of electrolytes, strict input-output, daily weight check for at least 1 week, periodic review of sodium intake from all sources, and avoidance of sodium bicarbonate boluses could help recognize and prevent hypernatremia. The use of humidification in an incubator, and avoidance of resuscitation in an open warmer or early transfer to an incubator reduce trans-epidermal losses in ELBW neonates. The key to the successful management of hypernatremia is careful titration of fluids intake with frequent monitoring of electrolytes. In infants who are discharged from newborn nurseries or those who are exclusively lactating should be followed within 3–5 days of discharge to check weight loss, ongoing feeding issues, or other signs of hypernatremia.

Mothers’ lactation support and education of health care workers, including physicians, midwives, nurses, and allied health care visitors, are essential to identify at-risk infants [76]. The calculations and clinical scenarios presented in this article are just examples, and each patient should be individually assessed. Fluid management is tailored for a steady decline in serum sodium level to prevent neurological complications.

The authors have no conflicts of interest to disclose.

No funding was secured for this study. The authors have no financial relationships relevant to this article to disclose.

Naveed Ur Rehman Durrani contributed to concept designs, analysis, and interpretation, drafted the manuscript, critically revised the manuscript, and gave final approval.

Abubakr Imam and Naharmal Soni contributed to analysis and interpretation, critically revised the manuscript, and gave final approval.

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