Part A: Fundamentals

INTRODUCTION

Successful resuscitation of the newborn nearly always begins with the establishment of a patent airway through which gas exchange will occur. However, the neonatal airway may be compromised by a number of developmental anomalies that make resuscitation challenging. Some of these anomalies are relatively benign and respond to simple maneuvers to achieve an airway. On the other end of the spectrum are other anomalies that may be lethal despite prenatal diagnosis and delivery at a center with advanced airway management capability. In either case, delivery room management will be influenced by the severity of the anomaly and the resulting degree of airway obstruction. Appropriate interventions in the delivery room may range from the placement of an ancillary device to maintain patency of the airway to the coordinated, multidisciplinary surgical intervention while the infant continues to be supported by the placental circulation. This chapter reviews the differential diagnosis of newborn airway obstruction and describes the overall approach to delivery room management of airway anomalies that range from mild to severe.

DIFFERENTIAL DIAGNOSIS

Obstruction of the neonatal airway may occur at many different levels. Choanal atresia is an upper airway anomaly that may cause respiratory distress immediately after birth or on initiation of early feeding attempts.¹ Choanal atresia most often is caused by bony obstruction and may affect either 1 or both sides of the nasal passages.² Choanal atresia may be isolated or a component of CHARGE association (coloboma, heart defect, atresia choanae [also known as choanal atresia], retarded growth and development, genital abnormality, and ear abnormality).³ There are other, rarer anatomic obstructive processes at the level of the nose in the neonate, ranging from the solid (glioma, rhabdomyosarcoma, and other tumors) to the cystic (dermoid and epidermoid cysts and meningoencephaloceles).

The development of the jaw and tongue may also influence initial airway management during resuscitation. Micrognathia may be seen as an associated finding with other disorders, including trisomies 13 and 18 and Treacher Collins syndrome. Macroglossia most commonly presents as part of a constellation of developmental anomalies, as would be the case in Beckwith-Wiedemann syndrome, trisomy 21, and congenital hypothyroidism. However, macroglossia also may represent underlying pathology in the tongue itself (tumor or vascular malformation) or underdevelopment of the mandible or maxillae.⁴ The combination of micrognathia, cleft palate, and upper airway obstruction defines the Pierre Robin sequence.

The newborn may present with bilateral congenital paralysis of the vocal cords. Although this typically does not result in true obstruction of the airway, the neonate may cough recurrently and develop respiratory difficulties with feedings. In congenital vocal cord paralysis, the cords are left in the open position, leaving the neonate potentially unable to protect the airway.⁵ Although not a usual cause of airway obstruction, appropriate airway evaluations should be performed. Likewise, tracheoesophageal fistula typically does not cause an anatomical airway obstruction. However, the newborn with associated esophageal atresia will be unable to clear oral secretions, which may pool in the posterior pharynx and cause a viscous obstruction to the airway.

Congenital high airway obstruction syndrome (CHAOS) may be diagnosed prenatally as either an isolated finding or associated with other anomalies. The level of the airway obstruction may be supraglottic, glottic, or infraglottic and range from laryngeal to tracheal obstruction. The true incidence of this syndrome is unknown but IS considered rare.⁶

Cystic hygromas are nonmalignant malformations of dilated cystic lymphatic vessels. In the cervical area, they may cause external compression of the larynx or trachea and subsequent obstruction. Chromosomal anomalies, including trisomies 18 and 21, Noonan, and Turner syndromes may be seen in a high percentage of cases.

The most common location for teratomas in the neonate is the sacrococcygeal region. However, these tumors may be found in the cervical area and contribute significantly to airway obstruction. The teratomas may have a variety of tissue present, including every embryonal tissue. The malignant potential of these tumors is unclear (Table 67-1).⁷

Prior to Delivery

Many of the diagnoses that result in partial or complete airway obstruction may be identified prenatally, thus allowing for consultation with appropriate personnel who may be involved in the initial resuscitation and care of the newborn.

PARTIAL AIRWAY OBSTRUCTION

Pierre Robin sequence and tracheoesophageal fistula are diagnoses that may be identified prenatally, and consultation with a neonatologist should be considered. During the prenatal consultation, the discussion should include the necessity of airway patency evaluation shortly after birth. If the baby is suspected of having Pierre Robin sequence, it is appropriate to mention that the infant may breathe more reliably in the prone position or may need initial airway support with a nasopharyngeal airway, endotracheal intubation, or placement of a laryngeal mask airway (LMA). The baby with suspected tracheal esophageal fistula likely will require the placement of a suction catheter into the proximal esophageal pouch to assist in clearance of viscous oral secretions.

COMPLETE AIRWAY OBSTRUCTION

If either a large neck mass or congenital high airway obstruction is diagnosed prenatally, referral to a center with expertise in immediate airway management of the fetus is appropriate. Prenatal imaging (ultrasound/magnetic resonance imaging [MRI]) findings that would suggest airway compromise from a cervical teratoma or cystic hygroma would include polyhydramnios (from esophageal compression), tracheal deviation, and a heterogeneous or cystic mass in the anterior cervical region. Prenatal findings consistent with congenital high airway obstruction would include a dilated proximal airway, lung hypertrophy, downward displacement of the diaphragm, ascites, or hydrops. During prenatal consultation, a medical geneticist should be involved to determine if there are associated findings or a syndromic component to the diagnosis. A multidisciplinary team will be needed to determine the optimal method of delivery and the potential need to resuscitate the infant while supported by the placental circulation (ex utero intrapartum treatment, or EXIT).⁸

EQUIPMENT PREPARATION

There should be at least 1 area with close approximation to labor and delivery where neonatal resuscitation occurs. That location should be stocked with all the necessary equipment required to perform a successful resuscitation. For the purposes of this chapter, the focus is on the equipment required to manage the newborn’s airway. Prenatally diagnosed airway issues allow for time and organization of materials that may facilitate the ease of resuscitation. It is an absolute necessity to have immediately available, well-organized airway assistance equipment. Table 67-2 lists the equipment that may be required for airway support.

TECHNIQUE

Providers taking part in neonatal resuscitation must be proficient in delivering appropriate bag mask ventilation, a skill that is emphasized during Neonatal Resuscitation Program (NRP)⁹ training. An improvement in heart rate is a reliable indicator of effective delivery of bag mask ventilation. It is important to learn how to troubleshoot ineffective ventilation, which should be recognized when no improvement in heart rate is seen despite initial positive pressure ventilation attempts. A mnemonic proposed by the NRP for correcting ineffective ventilation is MR.SOPA, described in Table 67-3.

SPECIAL CONSIDERATIONS

Meconium-Stained Amniotic Fluid

The Neonatal Resuscitation Program proposes an algorithm for the resuscitation of the neonate born through meconium-stained amniotic fluid. The algorithm begins with a rapid assessment of the newborn’s activity level. Resuscitative measures for the active, vigorous newborn are different from those for the newborn with respiratory depression. The current recommendation is that the vigorous baby has the mouth and nose cleared of secretions if any obstruction is suspected and then routine resuscitative measures if necessary. The nonvigorous baby should have both the mouth and trachea suctioned. It is vitally important to monitor the nonvigorous newborn’s heart rate during resuscitation. If the infant has prolonged bradycardia during attempts at tracheal suctioning, it is appropriate to consider bag mask ventilation even if the airway has not been fully cleared of meconium.

Partial Airway Obstruction

Choanal Atresia

The baby with bilateral choanal atresia will have labored respirations when the mouth is partially or fully closed. If the diagnosis is suspected based on the inability to pass a suction catheter through the nasal passages, placement of an oral airway and monitoring with pulse oximetry are appropriate while waiting for an evaluation from those in otolaryngology.

Pierre Robin Sequence

The neonate with Pierre Robin sequence may present challenges from the perspective of airway patency and maintenance. If the baby is noted to have intermittent obstructive apnea, placing the patient prone while monitored with pulse oximetry may relieve posterior pharyngeal obstruction. It may be necessary to consider an alternate airway if the patient is persistently bradycardic despite attempts at bag mask ventilation. Endotracheal intubation may be considered; however, if anatomically challenging, a size 1.0 laryngeal mask airway may be placed if the patient is greater than 2 kg. A nasopharyngeal airway can also be effective and is achieved by passing a small (2.5F) endotracheal tube through the nose and into the pharynx distal to the base of the tongue.

Macroglossia

Occasionally, the newborn with macroglossia will have a partial airway obstruction. This can be managed effectively with the placement of an oral airway.

Tracheal Esophageal Fistulae

The diagnosis of tracheal esophageal fistula may be made prenatally or shortly after birth. Clinical suspicion of this diagnosis is raised in a newborn with copious oral secretions. The baby may experience intermittent respiratory distress from the resultant inability to clear secretions from the airway. Placement of a suction catheter into the proximal esophageal pouch may be both diagnostic on imaging studies and, when connected to suction, alleviate the pooling of secretions in the pharynx.

Complete Obstruction

If the diagnosis of cystic hygroma, cervical teratoma, or CHAOS was identified prenatally, the time of birth will involve multiple medical and surgical services to establish an airway in the neonate. An EXIT procedure may be planned to achieve an airway while the infant is supported on maternal circulation. Unfortunately, for the neonate with a cystic hygroma, cervical teratoma, or CHAOS that was not identified prenatally, supporting ventilation should be attempted while emergent airway support is requested from the appropriate surgical service.

REFERENCES

INTRODUCTION

The transition to breathing for the hydropic infant after birth is a particularly tenuous situation. The delivery room management of hydrops can be a critical period of intervention and a highly intense event with a critically sick infant requiring extensive resuscitation and multiple procedures immediately following delivery.¹ The basic principles for resuscitation of high-risk newborns still apply. However, because of the possibility of pleural effusions and ascites in hydrops, the team must be prepared to perform two additional procedures that are not commonly performed by delivery room personnel: thoracentesis and paracentesis. This chapter outlines the overall approach to delivery room management for hydrops and provides detailed descriptions of these two procedures.

PREPARATION FOR DELIVERY

Prenatal Counseling

Prior to delivery, appropriate counseling of the family may involve discussion of the etiology of hydrops, if known, and the prognosis.² In some situations, hydrops may be an end-stage process, and comfort care after delivery may be a reasonable alternative to intensive resuscitation. This decision can be made prior to delivery with informed consent of the parents, allowing them to hold the infant soon after birth and to provide comfort. Prognosis in hydrops is dependent on the etiology, although the etiology may be indeterminate in about a quarter of cases. The prognosis can be discussed prior to delivery if time is available.

If resuscitation is planned, counseling of the parents should involve explaining the procedures that may be carried out in the delivery room. The delivery room will be a busy and intense environment; thus, preparation of the parents may help to relieve some degree of anxiety.

Delivery Room Staff

The makeup of the resuscitation team may vary by institution. Table 68-1 offers a potential delineation of roles that can be modified depending on availability of specific clinical personnel. The expected duties of clinicians may vary by institution, and this table can serve as a template for developing protocols that are more specific. However, it should be noted that the list of tasks is extensive, and a team consisting of at least 5, and possibly more, members is not an unreasonable expectation for this scenario.

Delivery Room Equipment

The equipment necessary for delivery room management of an infant with hydrops will include the basic equipment necessary for resuscitation of any high-risk infant, including a radiant warmer, and equipment for intubation and airway management. Furthermore, as the likelihood for volume resuscitation and medications may be high, supplies for umbilical line placement should be readily available. Difficulty with ventilation in hydrops may lead to the need for paracentesis or thoracentesis, and supplies for these procedures should also be prepared. The typical equipment used for these procedures is shown in Figure 68-1. A list of other equipment that may be used in the resuscitation of hydropic infants is provided in Table 68-2.

AIRWAY/BREATHING

As in all neonatal resuscitation, airway and breathing should be the first priority. Assessment and management should generally follow the procedures as described previously. However, there are several special considerations that can complicate management of the airway and ventilation in an infant with hydrops.

Edema

There may be a significant amount of soft tissue edema caused by hydrops that can distort both external and internal anatomy.

Congenital Airway Malformation

Congenital Airway Malformation may be a possible etiology of hydrops. Therefore, it is important that a clinician who is skilled in intubation be assigned the task of airway management. A smaller endotracheal tube may be necessary if there is significant edema. If airway abnormalities are expected, involvement of a pediatric otolaryngologist or anesthesiologist in the delivery room may be warranted.

Asphyxia

Asphyxia commonly accompanies hydrops, so meconium may be present at delivery, and intratracheal suctioning may need to be performed in accordance with the Neonatal Resuscitation Program (NRP) guidelines.

Intubation

In contrast to a typical resuscitation, a plan to immediately intubate and start positive pressure ventilation is a reasonable approach because mask ventilation may be ineffective as a result of generalized edema and decreased lung compliance. Typical rules of thumb for determining length of endotracheal tube placement may not be reliable because of distortion of anatomy. Thus, placement of the endotracheal tube should be based on visualization of passage of the tube through the vocal cords or postintubation assessment using end-tidal CO₂ monitors and auscultation.

Ventilator Support

Because there can be significant effusions, higher peak inspiratory pressures may be needed for adequate ventilation due to both the pleural effusions and the possibility of pulmonary hypoplasia. Limiting the use of excessive oxygen has been a growing priority in neonatology. However, if anemia is the cause of hydrops, there may be reduced oxygen-carrying capacity, and increasing the fraction of inspired air (FiO₂) more readily than in other scenarios may be reasonable.

Paracentesis/Thoracentesis

If resuscitation efforts are not effective despite the usual strategies, thoracentesis or paracentesis may be necessary. The steps for these two procedures are outlined in this chapter.

CIRCULATION

Anemia

The need for circulatory support with volume resuscitation and medications is likely in moderate-to-severe hydrops. When fetal anemia is known to be the cause of hydrops, blood for transfusion can be prepared and should be ready in the delivery room. It is best to use O-negative, cytomegalovirus (CMV)-negative, irradiated, packed red blood cells cross-matched against the mother’s blood. In any case of hydrops, if blood is not readily available in the delivery room, procedures for quick preparation of blood from the blood bank would be prudent. Personnel should be prepared for umbilical venous catheterization and/or blood transfusion.

Umbilical Vein Catheterization

In an emergency, umbilical vein catheterization is often the quickest method for establishing vascular access. If the etiology of hydrops is known to be anemia and there is evidence of volume depletion, the patient can receive a blood transfusion prior to obtaining laboratory results.

Umbilical Artery Catheterization

If enough personnel and resources are available, umbilical arterial catheterization to facilitate ongoing laboratory collection and blood pressure transduction may be beneficial. It will also allow for quick collection of blood for laboratory evaluation, including obtaining blood gas and hematocrit values. This will also facilitate partial exchange transfusion, which may be ideal in cases of severe anemia without significant volume depletion.

Myocardial Dysfunction

Myocardial dysfunction (including heart block and cardiomyopathy) may be present as the primary cause of hydrops or as a result of pericardial effusions. Although delivery room management may not be able to completely address this dysfunction, quick establishment of vascular access for medications may help to assist in optimal resuscitation. Electrocardiographic (ECG) leads will allow for detecting arrhythmias that may require intervention. Furthermore, ECG leads will help provide continuous assessment of heart rate, particularly if pulse oximetry is difficult to interpret because of subcutaneous edema. If cardiac complications (or need for pericardiocentesis) are anticipated, arrangements should be made to have a pediatric cardiology team (as well as an echocardiogram, defibrillator, or pacing equipment) available at the delivery.

EFFUSIONS

If ventilation is not effective despite intubation and positive pressure ventilation with higher inspiratory pressures, it is possible that pleural or peritoneal effusions may be interfering with ventilation. If this is the case, thoracentesis or paracentesis may be indicated. Deciding which procedure to perform first depends on the history and clinical assessment. If there are known to be large pleural effusions, thoracentesis may be the first step. Based on the relative frequencies of significant effusions in hydrops, paracentesis is often the more likely procedure to be performed first.

Paracentesis

If the abdomen is clearly distended and taut and ventilation is ineffective, paracentesis may be indicated as the first step. The steps for paracentesis are shown in Figure 68-2. The needle should be inserted into the lower right or left abdomen lateral to the rectus muscle to avoid hitting the liver or spleen, which may be enlarged. When fluid begins to flow through the hub of the needle, the catheter can be gently advanced as the stylet is withdrawn. The catheter can then be connected to the tubing, 3-way stopcock, and syringe. Fluid can be withdrawn with a syringe and collected for laboratory testing.

The purpose of the procedure is not to remove all of the ascites fluid as this may lead to circulatory instability and may ultimately be ineffective. Rather, the goal is to remove a sufficient amount of fluid (approximately 10–20 mL/kg) to assist in easing ventilator management. The amount of fluid to be removed can be based on an assessment of the decrease in abdominal distension/tautness and improvement in clinical status. In addition, usually there is communication between the peritoneal and the pleural spaces, so paracentesis may remove some of the pleural fluid. Once a sufficient amount of fluid has been removed, the catheter can be taped in place and the stopcock turned to the off position to allow later withdrawal of fluid if necessary. If a significant amount of fluid is removed, the tips of previously placed umbilical catheters may move, and their positions should be verified.

Thoracentesis

The steps for thoracentesis are shown in Figure 68-3. The intravenous catheter needle is inserted into the fourth or fifth intercostal space at the midaxillary line and directed posteriorly. To avoid the blood vessels and nerves that run just below the rib, the needle should be inserted just above it. When fluid begins to flow through the hub of the needle, the catheter can be gently advanced as the stylet is withdrawn. The catheter can then be connected to the tubing, 3-way stopcock, and syringe. Fluid can be withdrawn with a syringe to alleviate pressure. Note that removal of pleural fluid may not necessarily improve lung function if pulmonary hypoplasia or pulmonary edema is present. If desired, pleural fluid can be collected for laboratory testing, which can include cell count, culture, and estimation of protein content.

Chest Tube

In some cases of hydrops, thoracentesis with a small catheter may not be enough for resuscitation. Furthermore, because of the high pressures required for resuscitation, pneumothorax may be a potential occurrence. Therefore, preparation for chest tube placement for either fluid removal or pneumothorax may be necessary.

One quick method of chest tube placement utilizes a blunt-tip safety chest tube kit (as illustrated in Figure 68-4). This method is quicker than using a hemostat for dissection into the pleural space and therefore easier to place in the delivery room setting if necessary. First, the fourth or fifth intercostal space at the anterior axillary line is located. The length of chest tube insertion can be estimated by measuring the distance from the apex of the lung to the insertion site. After sterile preparation of the area, a scalpel is used to make a one-eighth to one-quarter inch incision overlying the space. The safety trocar is pushed into the incision and interspace, palpated above the rib. The trocar can be removed as the chest tube is held firmly in place. The tube is then advanced to the estimated length or approximately 3–4 cm for a term infant.

Pneumothorax

If the indication for the chest tube is a pneumothorax, the tip should be aimed anteriorly toward the second intercostal space so that the tip will lie at the highest point of the infant’s chest when lying supine. The tube is then connected to a water-seal vacuum drainage system and secured with suture and dressing.

Pleural Drainage

If the indication for the chest tube is to drain a pleural effusion, the tube can be directed posteriorly. Prior to connection to the vacuum system, a syringe can be used to obtain fluid for laboratory testing if desired. After the infant is stabilized, a chest x-ray should be obtained to confirm proper placement of the chest tube.

OTHER CONSIDERATIONS

Hypothermia

As intense, prolonged resuscitations can often be associated with unintended hypothermia, procedures that allow for relatively easy temperature monitoring and regulation should be implemented. The radiant warmer should be turned on to the maximum heat setting prior to delivery, and if possible, arrangements should be made to optimize the ambient temperature in the delivery room itself. Using a plastic wrap and a chemical warming mattress are other potential considerations. A continuous-temperature probe can be placed to also assist in temperature monitoring and regulation.

Hypoglycemia

Hypoglycemia may often occur soon after birth in infants with hydrops. Thus, glucose measurements should be obtained, and initiating an intravenous dextrose infusion should be considered as soon as feasible.

CONCLUSION

The delivery room management of an infant with hydrops is complex and requires skilled personnel who are appropriately trained in advanced resuscitation techniques. In addition to airway management and circulatory support, the team should be ready to perform additional procedures that may be required in the delivery room, such as thoracentesis and paracentesis. Proper preparation and anticipation of the procedures that may be necessary are essential for optimal resuscitation of an infant with hydrops.

REFERENCES

INTRODUCTION

Background

Maintenance of normal fluid and electrolyte balance for the first few days of life in neonatal intensive care unit (NICU) patients, specifically those who cannot feed orally, is an important part of their management. Indeed, it is a significant and challenging part of NICU admission orders. Neonates initially should be in good fluid and electrolyte balance immediately after birth. Exceptions can and do occur rarely but need to be recognized in a timely fashion. At birth, babies have excess total body water that they need to diurese. Despite this, they generally have normal serum electrolytes, which means that they also have increased total body sodium. Thus, initial salt and water requirements are nil. However, sick neonates in an NICU usually need intravenous access, and some fluid may be needed to keep this patent stable. Furthermore, they often need glucose, calcium, protein, and so on, and if not feeding, intravenous fluids may be needed to provide these items. Thus, the goals of initial fluid management are as follows:

1. Prevent excessive weight loss and dehydration, which can result in hypotension, cell damage, hyperkalemia, and intraventricular hemorrhage (IVH).

2. Allow appropriate diuresis while avoiding salt and water overload, which may be associated with pulmonary edema, prolonged ductal patency, and an increased risk of chronic lung disease.

3. Keep indwelling catheters patent.

4. Provide adequate calcium, glucose, and amino acid (AA) delivery.

5. Initiate enteral nutrition as soon as possible, preferably with maternal milk.

Maternal History

Occasionally, the maternal history can be an indicator of abnormal fluid and electrolyte status in the fetus and neonate. Some examples of maternal indicators of possible abnormal fluid and electrolyte balance include

1. Renal diseases with abnormal electrolytes;

2. Diuretic therapy;

3. Endocrine disorders (eg, diabetes, hypoparathyroidism); or

4. Malnutrition or very abnormal diet.

Fetal Findings

Rarely, there will be fetal evidence of increased risk for hyponatremia in the newborn. Findings on fetal ultrasonography suggestive of renal disease, such as

1. Oligohydramnios;

2. Renal cystic dysplasia;

3. Marked hydronephrosis/hydroureter; or

4. Inability to visualize a fetal bladder, and so on.

Neonatal Examination

Although there are usually no specific physical examination findings diagnostic of fluid and electrolyte imbalances, there can be findings suggestive of abnormal status:

1. Edema/anasarca;

2. Ascites, abdominal/flank masses;

3. Very immature skin (translucent red and shiny) in extremely low gestational age neonate (ELGAN);

4. Skin disorders with open bullæ, cracked skin, and the like; or

5. Open spinal or abdominal wall defect.

Laboratory

In general, the newborn infant, even the very premature patient, does not need serum electrolytes measured immediately after birth. Initially, a neonate’s electrolytes and serum urea nitrogen (BUN)/creatinine should reflect the mother’s status. Patients with a history or physical findings such as those mentioned may need to have electrolyte panels checked. Note that in the face of normal placental and maternal renal function, a totally anephric neonate will have a normal (ie, maternal) creatinine level at birth.

Differential Diagnosis/Diagnostic Algorithm: This is the same as previously mentioned. Abnormal initial electrolytes, if such values are obtained, usually indicate significant maternal disease, maternal medications, or placental dysfunction.

Exclusions/Contraindications: The major exclusions or contraindication to standard fluid and electrolyte management in the newborn would be underlying significant renal dysfunction and the abnormal findings listed previously.

TREATMENT/PROCEDURE

Consent/Assent/Ethical Considerations

Most units consider peripheral intravenous lines and umbilical catheters to be covered by the general consent for admission to the NICU. However, most consider central venous and peripheral arterial catheters (both percutaneously and surgically inserted) as more invasive and thus requiring separate informed consent for these procedures.

Monitoring for treatment

1. Intake and Output (I&O) must be monitored strictly, especially in the smallest patients.

2. Weights should be charted no less than daily and may need to be checked more frequently in high-risk situations. For this, the use of bed scales may be beneficial.

3. Glucose should be monitored closely, preferably with bedside “point-of-care” technology to provide rapid data and minimize blood loss. Glucose levels should be checked on admission.

   If the initial glucose value is low, then monitoring should be every half hour until stable on a consistent glucose infusion rate (GIR).

   If within normal range on admission, then follow glucose values every hour until stable on maintenance fluids.

   Thereafter, monitoring can be tapered to every 4 hours and then, if still stable, to daily and with changes in fluid administration.

4. Assuming none of the possible causes of abnormal in utero fluid and electrolyte balance exists, there is no need to check electrolytes immediately after birth. Baseline serum chemistries should be checked at about 12-hours of age and then every 12 hours for the first few days until stable on a consistent fluid regimen with normal renal function.

Initial Parenteral Fluid Management

Begin parenteral fluids for most neonates at the following:

1. For infants larger than 1500 g, provide 60–80 mL/kg daily;

2. For infants 1000–1500 g, provide 80 mL/kg daily;

3. For infants less than 1000 g, provide 100 mL/kg daily.

ELGANs may have immature skin as described previously and thus have markedly increased transepidermal fluid loss; these infants may have much higher fluid to avoid severe hypernatremic dehydration.

1. Starting at 120–150 mL/kg daily may be appropriate for these patients and, depending on their response, may go up to 200 mL/kg daily.

2. Humidified incubators may decrease insensible fluid loss, weight loss, and hypernatremia for these small babies.

Starting fluids should provide an approximate GIR of 4–6 mg/kg per minute (see Figure 69-1). This is usually accomplished with 10% dextrose in water (D10W), except for the ELGANs described previously, for whom much less-concentrated glucose would be appropriate. In general, infants less than about 750 g should start with 5% dextrose in water (D5W).

No sodium or potassium should be added to initial fluids.

Calcium gluconate should be added to avoid hypocalcemia; the target range is 200–400 mg/kg daily. The total may be limited by the resulting concentration of the parenteral solution. Calcium gluconate is irritating to veins, and extravasations can cause significant injury. We try to limit the amount in a peripheral intravenous solution to no more than 100 mg/dL; central venous catheter solutions may go up to 400 mg/dL.

Amino acids should be provided as soon as possible after birth to avoid protein catabolism. Neonates tolerate AA quite well and can start with as much AA as possible, given the limitations of solubility in intravenous solutions. This is usually about 2 g/dL for peripheral and 3 g/dL for central venous line solutions. Because neonates can lose more than 1 g/kg of protein daily if none is provided, AA should be added immediately in the highest concentration allowed.

Management Algorithm

Weight monitoring is needed to avoid excessive loss. Daily weights are adequate for most neonates, but twice-daily weights may be needed for ELGAN patients. Total weight loss should not exceed 10% of birth weight, and recent studies suggested that, with early hyperalimentation, may not need to exceed 6%. Weight should be plotted on appropriate growth curves. Excessive weight loss should result in a 10–20 mL/kg increase in daily intravenous rate.

Electrolyte monitoring should be done twice daily initially and again perhaps more frequently for ELGANs.

1. Hypernatremia must be watched for and responded to rapidly, again by increasing fluid administration by 10–20 mL/kg daily.

2. Hyponatremia in the first days of life almost always means free-water overload and not inadequate sodium intake. Thus, rather than treating this with added sodium in the parenteral solution, further fluid restriction is the best first step.

3. Nonoliguric hyperkalemia is a significant concern in ELGANs. There is some evidence that increased AA administration may minimize this. Nevertheless, do not add potassium to initial intravenous fluids until good urine output and renal function are ensured and then only add slowly with close monitoring of serum levels.

4. The safest and most effective way to provide calcium to infants is via the enteral route. This is another argument for initiating enteral nutrition as soon as possible.

The GIR should be calculated whenever intravenous lines are changed to avoid the risk of delivering either too much or too little glucose.

1. Too low a GIR can result in hypoglycemia and inadequate growth.

2. Too high a GIR can result in hyperglycemia, osmotic diuresis, increased carbon dioxide production, and liver injury. In general, try to keep the GIR no more than about 12 mg/kg per min.

3. The following are indications to increase fluid administration:

   • Excessive weight loss;

   • Gastroschisis/omphalocele;

   • Immature, sticky, translucent skin;

   • Polyuria;

   • Hyperglycemia;

   • Hypernatremia; and

   • Hyperkalemia.

4. Indications for decreasing fluid administration are as follows:

   • Asphyxia/cerebral edema;

   • Generalized body edema;

   • Oliguria (eg, renal failure, syndrome of inappropriate secretion of antidiuretic hormone [SIADH], indomethacin);

   • Heart failure or patent ductus arteriosus (PDA);

   • Pulmonary edema;

   • Excessive weight gain;

   • Hyperglycemia; and

   • Hyponatremia.

SUGGESTED READINGS

INTRODUCTION

Nutrition support plays a crucial role in the management of premature neonates. Parenteral nutrition (PN) especially has continued to have an impact on the care of neonates who are unable to ingest sufficient enteral calories and fluids. The use of PN has evolved in the neonatal intensive care unit (NICU) to minimize the metabolic complications that interrupt normal growth. To deliver PN to neonates, those involved in the ordering and delivery of PN need to be educated and trained to ensure safety and standardization.¹ This chapter provides a practical overview to provide optimal nutrition support to neonates in the NICU, keeping in mind the particular conditions and physiology of premature neonates.

INDICATIONS

Parenteral nutrition can be used as the sole source of nutrition and fluids for neonates. There are multiple conditions that can inhibit or limit the use of enteral nutrition. Patients can develop short-bowel syndrome from intestinal atresia, volvulus, or necrotizing enterocolitis. Motility issues can arise from Hirschsprung disease, meconium ileus, ileus as a result of generalized illness, or gastroschisis. Neonates with asphyxia or hypotension with use of vasopressors might not be clinically stable enough for the initiation of enteral nutrition. Preterm neonates on slowly advancing feedings will also require PN supplementation to obtain substantial calories and fluids until goal feedings have been reached. PN or enteral nutrition should be started within 24 hours after birth.^{2, 3, 4, and 5} More aggressive administration of both glucose and amino acids has led to the use of standard, starter, or “vanilla” total parenteral nutrition (TPN). Many of these solutions come premixed; many institutions still compound the mixture in the hospital pharmacy. These initial solutions usually contain 7.5% to 10% dextrose and 3% amino acids.⁶ The goal is to have a glucose infusion rate (GIR) of 6–8 mg/kg/min and amino acid administration of 2 to 3 g/kg/day.

ROUTE OF ADMINISTRATION

Peripheral venous access limits the osmolality of fluids that can be infused through it, which limits dextrose concentration to 12.5%. Increased osmolality that infuses through a peripheral catheter increases the risk of thrombophlebitis, although concomitant infusion of a fat emulsion can reduce venous irritation.^7,8 Central venous access, either through an umbilical venous catheter (UVC) or a peripherally inserted central catheter (PICC) is generally needed. Positioning of these catheters must be confirmed with an x-ray showing the tip terminating at the junction of the superior vena cava and right atrium of the heart. Continuous infusion of heparin 0.5 IU/kg/h has been shown to reduce occlusions of PICC lines in neonates and can be added directly to the PN fluid.^9,10

PARENTERAL NUTRITION COMPONENTS

Calories

There are many factors that can increase the metabolic demands of neonates, including increased heat loss, small for gestational age (SGA), fever, sepsis, respiratory distress, and the accelerated rate of growth. Neonates who receive a caloric intake as low as 70 kcal/kg/d have demonstrated a positive nitrogen balance. Weight gain can occur with parenteral intake of 80 to 130 kcal/kg/d if there is adequate protein intake. The caloric goal of premature neonates is 100 to 120 kcal/kg/d, and the goal of term neonates is 90–108 kcal/kg/d (Table 70-1).¹¹ Calorie utilization is maximized if given in balanced allotments of macronutrients. Carbohydrates should be the main source of calories at 40% to 50%, followed by lipids at 30% to 40% and protein at 10%–30% of the caloric intake.¹² Optimal calorie goals aim to sustain appropriate “catchup” growth. Excessive calorie intake must be avoided as this can result in excessive fat deposition in the subcutaneous tissue and liver as well as greater carbon dioxide production, which complicates any underlying respiratory conditions.¹³

Fluids

The nutritional and caloric composition is a particular focus when discussing TPN, but the volume that is delivered is just as crucial (Table 70-1). Premature neonates have increased fluid losses because of radiant warmers, phototherapy, increased skin permeability, and respiratory distress. As a result of these factors, the premature neonate has higher volume needs than the term neonate. If there is fluid restriction, the concentration of nutrients needs to be increased, resulting in high osmolarity and issues with solubility. To help improve tolerance of these high-osmolar solutions, the amino acid–dextrose solution is typically run over 24 hours so the infusion rate can be as low as possible. Fat emulsions are also better tolerated if infused over 18 to 24 hours.

Carbohydrates

For neonates, carbohydrate delivery in PN should begin at approximately 6 to 8 mg/kg/min and be advanced, as tolerated, to a goal of 10 to 14 mg/kg/min.¹² Dextrose is normally started at 10% concentration so that it will deliver a GIR around 7 mg/kg/min if infused at a rate of 100 mL/kg/d. As the GIR is increased, a trace amount of glucosuria is not uncommon, but the GIR may need to be decreased as serum glucose levels are also monitored (Table 70-1). Hyperglycemia in neonates can be associated with complications, including death, infections, visual problems, and intraventricular hemorrhage. The routine use of insulin to help prevent hyperglycemia in premature neonates has not been well established and can be associated with risk, such as lactic acidosis and death.^11,14,15 Continuous insulin infusions at 0.01 to 0.1 units/kg/h may be necessary for managing hyperglycemia in neonates.¹²

Protein

Commercial pediatric amino acid solutions are formulated to result in plasma amino acid profiles that are comparable to breast-fed infants. These formulations contain taurine, tyrosine, histidine, aspartic acid, and glutamic acid and contain less glycine, methionine, and phenylalanine than adult amino acid formulations.¹¹ Cysteine, a conditionally essential amino acid for neonates, is not added to pediatric amino acid formulations because of its short shelf life. Cysteine hydrochloride can be added to PN fluid at a dose of 40 mg/g of amino acids. Carnitine, required for optimal fatty acid metabolism, is also not added to pediatric amino acid formulations. There have not been any convincing studies to demonstrate that carnitine has any effect on lipid utilization and ketogenesis, although fatty acid oxidation is impaired if the tissue carnitine level falls below 10% of normal.¹⁶ Still, it has become practice to add L-carnitine 2 to 5 mg/kg/d to PN fluids, especially for neonates having difficulty with hypertriglyceridemia.¹² This dose is the same quantity received from breast milk and infant formula.¹⁷ As stated previously, amino acids should be started within the first 24 hours of life and then advanced to the goal (Table 70-1). Newer retrospective data argue for starting amino acids within the first few hours of life.¹⁸

Fat

Fat constitutes a high-caloric nutrient source in any diet. Fat emulsions are currently available as 10% or 20% soy or soy-safflower oil. The use of 20% emulsion is preferred because it is more calorically dense yet has the same phospholipid concentration, has improved clearance of triglycerides and phospholipids, and has the same osmolarity as the 10% emulsion. These emulsions can prevent essential fatty acid deficiency (EFAD) at a minimum rate of 0.5 to 1 g/kg/d in the presence of adequate energy intake. If a neonate is in an energy-deficient state, then EFAD may not be prevented at this minimal rate because essential fatty acids will be oxidized to meet energy needs. Fat emulsions should be started within 3 days of life to prevent EFAD. Fat emulsions are safe to start within the first 24 hours of life and can be increased to a goal rate (Table 70-1). Fat emulsion delivery at a continuous rate over 24 hours optimizes lipid clearance. The maximum infusion rate should not exceed 0.15 g/kg/h, but this rate may need to be lower in very low birth weight infants or SGA infants. Heparin also stimulates the release of lipoprotein lipase, which may improve lipid clearance.

Jaundice and sepsis are not contraindications for using fat emulsions. There is a theoretic risk that fatty acids can displace bilirubin from albumin, resulting in increased serum unconjugated (free) bilirubin concentration, thus increasing the risk of kernicterus. Fat emulsion given at a rate of 1 to 4 g/kg/d did not show any effect on the bilirubin and albumin levels in neonates.¹⁹ Even with these findings, if the unconjugated bilirubin concentration approaches the level indicating an exchange transfusion, it is recommended that the fat emulsion rate should be decreased to 0.5 to 2 g/kg/d, and the rate should not be advanced until the bilirubin has decreased to 50% of the exchange transfusion level. Serum triglyceride levels can increase in the presence of bacterial sepsis, trauma, and stress and should be monitored. Although the risk of infection increases with the administration of fatty acids, this risk is not reason enough to avoid the use of fat emulsion.²⁰

Electrolytes and Minerals

Close monitoring of electrolyte status is essential in neonates as daily adjustments are often necessary with the initiation of PN. The addition of electrolytes to PN may be deferred until the second day of life until regular urine output is ensured. Sodium is usually added once diuresis has begun, and potassium is added once good urine output and normal kidney function are established. Table 70-2 provides reference ranges of electrolyte requirements.

Calcium and phosphorus play a major role in neonatal PN because preterm neonates have not fully mineralized their bones. During the first 2 days of life, PN can contain less than maintenance phosphorus because of the concern of hyperphosphatemia. The maintenance dosing can be found in Table 70-2 but can also be listed as milligrams per liter, in which case it would be dosed at calcium 500 to 600 mg/L and phosphorus 350–500 mg/L of PN. The goal calcium-to-phosphorus ratio is 1.3 to 1.7:1. The difficulty with calcium and phosphorus administration is the concern of solubility. The solubility curves of calcium and phosphorus are multifactorial, but it has been clearly established that the pH of the solution plays a key role, so increasing the amount of amino acids, and possibly adding cysteine, as well as increasing dextrose can help increase the solubility.²¹

Trace Elements

There is no reason to avoid providing trace elements to neonates requiring short-term PN. The concentrations and composition of pediatric formulations are similar. Recommended dosing can be found in Table 70-3. Individual trace element products would need to be used to meet trace element needs because commercially available multitrace products would not meet these needs.

Zinc is important in cell growth and development. Additional zinc may be required in cases with elevated urinary and stool zinc excretion.

Copper is an essential component of several key enzymes. Additional copper may be required because of increased biliary losses secondary to a jejunostomy or biliary drain. Copper has been held from PN in patients with cholestasis, but cases of copper deficiency have been reported.²² If cholestasis develops, copper can be withheld from PN; then, monitoring copper and ceruloplasmin levels is crucial, and copper can be restarted individually if levels become deficient. Some recommend maintaining a dose of 20 μg/kg/d, but others have decreased the rate to only 10 μg/kg/day.^22,23

Manganese is a component of several enzymes. Manganese deficiency has not been documented, although toxicity has been documented. Individually supplementing manganese should be done with caution, especially because it is already a contaminant of PN solutions. Manganese has been shown on magnetic resonance imaging (MRI) to deposit in the basal ganglia, leading to central nervous system symptoms such as Parkinsonism.

Chromium potentiates the action of insulin and has a key role in glucose, protein, and lipid metabolism. Chromium intake can be decreased in patients with renal impairment. Chromium is also a major contaminant of PN solutions and does not need to be routinely added to PN.

Selenium is a component of glutathione peroxidase. Supplementation is recommended in patients who continue on PN for longer than 30 days; levels should be monitored after that time. The dose should be decreased when renal dysfunction is present.

Multivitamins

See Table 70-4 for recommended dosing of multivitamins.

MONITORING

The guidelines for metabolic monitoring of neonates while on PN are shown in Table 70-5.

Catheter Occlusion

Central venous catheters used for the administration of PN can become occluded for several reasons. A thrombus or clot is the most common cause of a catheter occlusion. For this reason, it is recommended to add 0.25 to 1 U/L of heparin to the PN solution.²⁴ If a thrombus is occluding the catheter, then 2 mg/2 mL alteplase can be instilled into the catheter at 110% of the catheter volume and left to dwell in the catheter for 30 minutes. If there is no response, leave in place for 2 hours; if no response, give a second dose, which can dwell up to an additional 2 hours. Lipid deposition can also occlude a catheter. In this case, 70% ethanol can be instilled in the catheter for 1 to 2 hours; the dose is 0.55 mL/kg (to a maximum of 3 mL). Calcium/phosphorus precipitate can be cleared from a catheter using 0.5 mL of 0.1 N hydrochloric acid. Acidic drug precipitate has been cleared with 0.2 to 1 mL of 0.1 N hydrochloric acid, and basic drug precipitate has been cleared from a catheter using 1 mL of 0.1 N sodium hydroxide or 1 mL of 1 mEq/L sodium bicarbonate.²⁵

Cholestasis

Neonates are at high risk for developing cholestasis because prematurity, low birth weight, sepsis, and limited enteral intake are all risk factors. PN can increase this risk because manganese, copper, and aluminum can all have hepatotoxic effects. Recent studies suggested that the proinflammatory omega-6 polysaturated fatty acids in plant oil–based lipid emulsions (Intralipid, Liposyn III) and the presence of phytosterols contribute to the development of hepatotoxicity.²⁶ Once a neonate on PN develops cholestasis, there are multiple strategies that can be implemented to help prevent and treat the cholestasis. The neonate must receive a pediatric amino acid formulation. Ensure that the neonate is not receiving excessive caloric intake. Decrease the fat emulsion to about 1 g/kg/d. Remove trace elements from the PN solution, while supplementing with zinc and selenium, then monitor copper and manganese serum levels and supplement individually if needed. Starting enteral feedings is the key to stimulate bile flow. Ursodeoxycholic acid 20 to 30 mg/kg/day given enterally is safe and effective and should be started as soon as possible once cholestasis is identified.²⁷

Aluminum

Aluminum has long been known to be a contaminant of PN solutions. Toxicity from aluminum can manifest with neurologic impairment, decreased bone mineralization, microcytic anemia, and cholestasis. Calcium and phosphorus solutions have the most contamination, which puts premature neonates at highest risk because of their high demand for these minerals and poor renal clearance of aluminum by neonates. As a result, the Food and Drug Administration (FDA) mandated specific labeling requirements.^28,29 Many organizations have also developed guidelines to help minimize the risk of aluminum toxicity.^30,31 It has been shown that the FDA regulations cannot be met with the current PN solutions available.³² To minimize the risk, the PN solutions with the least contamination can be purchased and used by pharmacies.³³

Weaning Parenteral Nutrition

The ultimate goal of PN is to wean the infant from it and transition to enteral nutrition as quickly and safely as possible. Table 70-6 illustrates a tactic to wean PN as enteral nutrition is gradually increased, yet administer adequate nutrition.

Basic TPN Calculations

Guidelines for calculating GIR and for calculating macronutrient calories are shown in Table 70-7.

REFERENCES

INDICATION

Clinical Findings

History

The protocols in this chapter are for neonates with very low birth weight (VLBW) (≤1500 g) who are clinically stable for initiation of enteral feedings. The goal is to initiate enteral feedings by day of life 3.

Physical

There should be no congenital gastrointestinal defects precluding enteral feedings.

Exclusions/Contraindications

1. Hemodynamic instability requiring volume resuscitation, dopamine > 5 μg/kg/min, or initiation of hydrocortisone

   1. Feeding should be delayed until hemodynamically stable for 24–48 hours.

   2. Patient may be started on feedings while on hydrocortisone (ie, weaning course of treatment) if the patient is hemodynamically stable.

2. Hemodynamically significant patent ductus arteriosus (PDA) requiring indomethacin treatment or surgical closure: Feeding should be delayed until 24–48 hours after indomethacin course is completed or surgery is completed.

3. Abdominal distension, signs of obstruction, abdominal discoloration consistent with peritonitis, or surgical abdomen

4. Large-volume gastric fluid, discolored (eg, bilious) gastric fluid

5. Sepsis, severe metabolic acidosis, hypoxia-asphyxia: Feeding should be delayed based on clinical evaluation.

PREPARATION

Consent

Per individual units’ policies, parental assent or informed consent may need to be obtained for use of banked donor breast milk if maternal breast milk (MBM) is not available.

Monitoring During Treatment

1. Cardiorespiratory and oxygen saturation monitoring is necessary during treatment.

2. Gastric residuals may be measured prior to each feeding per unit policy.

TREATMENT/PROCEDURE

Initiation

Colostrum Administration

1. The change from colostrum to transitional milk is individual. However, as a working definition, milk obtained from mothers during the first 7 days will be considered colostrum. During this time, fresh colostrum (not previously frozen) may be used.

2. If the infant is ready to begin enteral feedings, colostrum may be administered in trophic feedings given via gavage tube (see the sample feeding volume and advancement schedule).

3. If colostrum is available but the infant is not ready for enteral feedings, colostrum may be administered in the following fashion: Colostrum, 0.5 – 1 mL every 6 hours, may be delivered via syringe into the buccal pouch of the mouth or may be delivered via sterile cotton swab to the buccal cavity.

Enteral Feeding Choice

Maternal breast milk is the enteral feeding of choice unless contraindications for its use exist.

1. Possible contraindications for MBM use (individual units will have their own policies) are the following:

   1. Infant with galactosemia

   2. Mother with active untreated tuberculosis

   3. Mother receiving diagnostic or therapeutic radioactive isotopes or with exposure to radioactive materials

   4. Mother receiving antimetabolites or chemotherapeutic agents

   5. Mother positive for human immunodeficiency virus (HIV)

   6. Mother with active herpes lesion on breast(s). Milk may be used from unaffected breast.

   7. Mother with varicella determined to be potentially infectious to infant

   8. Mother with human T-cell leukemia virus type 1 (HTLV-1)

2. Breast pumping and hand expression should be initiated within the first 6 hours postpartum.

3. The value of colostrum should be emphasized: Fresh colostrum should be collected and used in the first feedings (see the section on colostrum administration).

4. Lactation consultation should occur, ideally, on the day of delivery or as soon as the mother is available (ie, if the baby has been transferred from another hospital).

If MBM is not available, pasteurized donor human milk is preferable to formula for initiation of feedings in very low birth weight (VLBW) infants.

If formula must be used, a 20-calorie/oz premature infant formula should be used.

Sample Feeding Volume and Advancement Schedule

A sample feeding volume and advancement schedule is presented in Table 71-1.

Management

Feeding Intolerance

1. Episodes of feeding intolerance are common for preterm infants with poor peristalsis. Clinical assessment and integration of numerous pieces of information are required to ascertain the implications and importance of findings.

2. The following are serious signs of clinical problems and important reasons to stop feeding, consistent with possible necrotizing enterocolitis (NEC) or sepsis. The physician should be immediately notified and the patient evaluated.

   1. Abdominal distention, new “visible loops,” abdominal discoloration

   2. Worsening clinical status, including hemodynamic or respiratory instability (eg, increasing bradycardia or apnea), poor perfusion, hypo- or hyperglycemia

   3. Bloody stools not associated with anal fissure

   4. Bloody gastric residual or emesis

3. Potentially serious signs of impending or developing problems that should trigger assessment by physician are the following:

   1. “Bilious” (green or yellow) gastric residuals: These may be associated with developing clinical problems or may simply indicate a mechanical issue such as the orogastric tube at or beyond the pyloric sphincter.

   2. “Large-volume” emesis: In a VLBW infant who has reached 50% of full-volume feedings, a large-volume emesis is considered to be 50% of the last feeding volume. Other factors, such as the color of the emesis, whether emesis is a new finding, changes in feeding regimen, and the clinical status of the infant should be assessed.

   3. Gastric residuals: The volume of gastric residual may or may not be indicative of looming problems. Gastric residuals should be evaluated in the context of the overall clinical assessment. Few data exist regarding the “normal” or “safe” volume of gastric residual in a feeding preterm infant.

Sample Algorithm

A sample algorithm for management of gastric residuals is presented in Figure 71-1.

REFERENCES

DIAGNOSIS/INDICATION

Clinical Background

Disorders of calcium metabolism frequently develop in neonates in the intensive care setting. Hypocalcemia is the most common. Hypocalcemia is defined as serum calcium below 8 mg/dL (ionized calcium < 1.1 mmol/L) in a full-term infant or serum calcium less than 7 mg/dL (ionized calcium < 1 mmol/L) in a preterm infant. The etiology and treatment of hypocalcemia is often determined by the age of onset.

Premature infants are at risk for poor mineral stores because the fetus accrues 80% of its calcium stores in the third trimester.¹ Similar accrual occurs for magnesium and phosphorus stores as well. Fetal parathyroid hormone is secreted in response to maternal calcium levels. After birth, there is a rapid drop in the serum calcium because of the loss of the transplacental infusion of calcium. The sudden removal of this calcium source requires the neonate to rely on endogenous parathyroid hormone production, ingested calcium, renal tubular reabsorption of calcium, and bone calcium stores. There is a physiologic nadir in the serum calcium level that occurs at 24–48 hours of life. In response to the falling calcium levels, there is a rise in the parathyroid hormone level, resulting in an increased serum calcium level. Abnormalities in this physiological response can lead to hypocalcemia in the neonate.

History

Maternal History

Key aspects of the maternal history include a history of gestational diabetes, maternal vitamin D deficiency, and maternal hypercalcemia from hyperparathyroidism or large intake of calcium carbonate in antacids.

Birth History

Key aspects of the birth history include premature gestational age, low birth weight, intrauterine growth restriction/small for gestational age, large for gestational age, and perinatal stress.

Patient History

Key aspects of the patient’s history include diuretic use, daily calcium and phosphorus intake, vitamin intake, fat malabsorption, liver dysfunction, renal disease, and use of parenteral nutrition.

Physical Examination

Signs of hypocalcemia include the following:

• irritability,

• jitteriness or tremulousness,

• facial spasms,

• tetany,

• stridor, and

• focal or generalized seizures.

  Nonspecific signs of hypocalcemia include

• apnea,

• tachycardia,

• cyanosis,

• emesis, and

• poor feeding.

Note that the Chvostek sign (tapping over the facial nerve at the angle of the jaw, resulting in a twitch of the nose or lips) or Trousseau sign (inflating the blood pressure cuff above systolic pressure for 2 minutes, leading to carpal muscle spasm) are not commonly seen in neonates.

Confirmatory Laboratory Studies

Specific laboratory tests obtained during a period of hypocalcemia will provide important diagnostic information regarding the underlying etiology. The following laboratory tests should be obtained when the infant is hypocalcemic (Table 72-1):

• serum calcium and ionized calcium,

• albumin,

• serum phosphorus,

• serum magnesium,

• intact parathyroid hormone (iPTH),

• urine calcium-to-creatinine ratio, and

• 25-hydroxyvitamin D level and 1,25-dihydroxyvitamin D level for late-onset or chronic hypocalcemia.

If a maternal etiology is suspected in early-onset hypocalcemia, the following are the recommended maternal laboratory tests:

• serum calcium,

• serum phosphorus,

• iPTH,

• 25-hydroxyvitamin D level.

  Additional baseline ancillary tests include

• an electrocardiogram to evaluate for prolongation of the QTc (corrected QT) interval or

• radiographs of the long bones or ribs to look for rachitic changes.

Serum albumin concentrations affect serum calcium concentrations; thus, the serum calcium concentration must be adjusted: Corrected calcium [mg/dL] = Measured total calcium (mg/dL) + 0.8 (Normal serum albumin [g/dL]) − Serum albumin [g/dL]). The amount of ionized calcium is inversely proportional to the serum pH. There is a direct pH effect; alkalosis leads to a lower-than-expected value of ionized calcium for the serum calcium concentration, and acidosis leads to a higher-than-expected ionized calcium value.

Differential Diagnosis/Diagnostic Algorithm

The etiology of neonatal hypocalcemia is classified based on age at presentation: early onset (<72 hours of life) or late onset (> 72 hours of life) (Table 72-2).

Early Onset

Early onset of neonatal hypocalcemia occurs prior to 72 hours of life.

Infant of a Diabetic Mother

The causes of hypocalcemia in an infant of a diabetic mother include

• reduced placental transfer of calcium because of increased maternal urinary excretion of calcium and magnesium;

• decreased neonatal parathyroid hormone secretion;

• elevated calcitonin levels in the first 24–48 hours of life; and

• decreased calcium absorption and decreased calcium intake after birth.

Severe Vitamin D Deficiency

Poor maternal vitamin D stores lead to poor neonatal vitamin D stores, resulting in hypocalcemia in the early newborn period.

Maternal Hyperparathyroidism

Maternal hyperparathyroidism leads to increased transplacental transfer of calcium to the fetus. Higher fetal calcium levels suppress fetal parathyroid hormone production, which can persist for several months after birth.

Prematurity

Premature infants have a blunted rise in parathyroid hormone in the first 24–48 hours of life. There is also physiologic resistance at the level of the kidney to phosphate secretion.

Perinatal Stress/Birth Asphyxia

With perinatal stress or birth asphyxia, there is an increased phosphate load from cell injury as well as elevated calcitonin levels, leading to hypocalcemia.

Exchange Transfusion

Citrate, an anticoagulant added to stored blood, complexes with calcium and reduces the amount of ionized calcium, leading to hypocalcemia. Hypocalcemia caused by citrate is not seen usually with small-volume (eg, 10–20 mL/kg) blood transfusions but can be seen with repeated or exchange transfusions because the amount of citrate is significantly higher.

Late Onset

Late onset of neonatal hypocalcemia occurs after 72 hours of life.

Hypoparathyroidism

Hypoparathyroidism results in hypocalcemia and hyperphosphatemia, along with decreased conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D via the 1-α-hydroxylase enzyme. Hypoparathyroidism may be transient (a few weeks) or prolonged. Transient hypoparathyroidism is caused by a lack of maturity of the parathyroid gland after birth or maternal diabetes mellitus and resolves in the first few weeks of life.

Prolonged hypoparathyroidism can be due to error in embryogenesis of the parathyroid gland, including DiGeorge syndrome (22q11.2 deletion, velocardiofacial syndrome); mitochondrial disorders (eg, Kerns-Sayre syndrome); and calcium-sensing receptor gain-of-function mutations for which the calcium set point at which parathyroid hormone is secreted is lower than normal. Insensitivity or end-organ resistance to parathyroid hormone can lead to clinical hypoparathyroidism in the setting of elevated serum parathyroid hormone concentrations.

Vitamin D Deficiency

Low 25-hydroxyvitamin D concentrations (<20 ng/dL) in neonates can be caused by poor maternal stores that lead to poor vitamin D stores in the infant, infants who are exclusively breast fed without vitamin D supplementation, and more rare causes, including diminished 1-α–hydroxylase activity in the kidney (caused by vitamin D–dependent rickets or renal disease) or loss of function of the vitamin D receptor. Hypocalcemia from vitamin D deficiency can occur without physical or radiographic evidence of rickets.

Hyperphosphatemia

Excessive phosphate intake in evaporated milk or cow’s milk formula creates a poorly soluble calcium salt, leading to decreased intestinal absorption of calcium and hypocalcemia.

Hypomagnesemia

Magnesium affects parathyroid hormone secretion and function. Hypomagnesemia can lead to impaired end-organ response to parathyroid hormone and diminished parathyroid hormone release. Hypocalcemia is refractory to calcium replacement therapy in the setting of hypomagnesemia.

Diuretic Therapy

Loop diuretics, such as furosemide, cause hypercalciuria by decreasing the tubular reabsorption of calcium, leading to hypocalcemia and bone demineralization.

TREATMENT

Initiation

Early-onset hypocalcemia in the first 72 hours of life is often asymptomatic, and expectant management is recommended unless the serum calcium is very low (total serum calcium < 6 mg/dL in preterm infant or < 7 mg/dL in term infant) or the neonate is symptomatic. In the symptomatic neonate, 10% calcium gluconate (elemental calcium 9.3 mg/mL) at a dose of 100 mg/kg over 5–10 minutes with continued monitoring of the heart rate and infusion site is recommended. The dose can be repeated if there is no clinical response in 10 minutes (total dose not to exceed 20 mg elemental calcium/kg).² After acute treatment is provided, maintenance calcium replacement therapy must be started. Maintenance calcium replacement can be given by adding calcium gluconate to the intravenous solution (50–75 mg elemental calcium/kg/d as a continuous drip or divided dose every 6 hours) or, if enteral feedings are tolerated, as calcium glubionate 50–100 mg elemental calcium/kg/d divided into 4–6 doses. Asymptomatic neonates can be managed by increasing the oral calcium intake using calcium glubionate (50–100 mg elemental calcium/kg/d divided into 4–6 doses) or calcium carbonate in divided doses every 4 to 6 hours and a low phosphorus formula such as Similac PM 60/40^¯ to establish an overall 4:1 ratio of calcium/phosphate intake. Neonates with hypoparathyroidism require treatment with calcitriol to allow absorption of enteral calcium; neonates with vitamin D deficiency rickets require treatment with ergocalciferol or cholecalciferol to restore vitamin D stores. Neonates with concurrent hypomagnesemia require magnesium supplementation to maintain appropriate serum magnesium levels.

Tests to Follow

Serum calcium or ionized calcium levels along with urine calcium and creatinine levels should be followed frequently and treatment modified to maintain eucalcemia (serum calcium in the low-normal range) and prevent hypercalciuria. Serum phosphate levels should also be followed in neonates with hypoparathyroidism. It is important to watch for side effects of treatment, including iatrogenic hypercalcemia, hypercalciuria, nephrocalcinosis, and renal insufficiency. Follow-up radiographs may be appropriate for infants with baseline rachitic changes.

Management Algorithm/Decision Tree

Indications for Discontinuation

Calcium supplementation should be adjusted to maintain eucalcemia and can be decreased when serum calcium concentrations are in the high-normal range to avoid hypercalcemia. Transient hypocalcemia may only require supplementation for a few days or few weeks; cases of prolonged hypocalcemia require many years, even lifelong, calcium replacement therapy. Hypocalcemia caused by diuretic use will resolve when the diuretic dose is sufficiently decreased or stopped, eliminating the need for calcium supplementation.

CONCLUSION/FOLLOW-UP

Aftercare Monitoring

Careful follow-up and monitoring of the neonate with hypocalcemia is required. Parents must be instructed on the signs and symptoms of hypocalcemia and situations in which the infant may be prone to hypocalcemia. Illness resulting in vomiting or diarrhea, poor enteral intake, and inability to tolerate oral calcium supplementation can result in a fall in the serum calcium level, necessitating frequent monitoring of the serum calcium and an increase in calcium supplementation. Neonates who no longer require daily calcium supplementation may be prone to hypocalcemia during illness or other stress (initiation or increase of diuretic therapy) and should have the serum calcium levels followed closely. Neonates with diuretic-induced hypocalcemia may require adjustment in calcium supplementation when doses of diuretics are increased or decreased.

Follow-up Tests

After discharge from neonatal intensive care, continued monitoring of serum calcium and phosphorus levels is required to adjust calcium supplementation. In neonates with vitamin D deficiency, repeat 25-hydroxyvitamin D levels should be obtained after the treatment course of vitamin D is complete. Follow-up radiographs may be appropriate to view resolution of rachitic changes.

Clinical Follow-up

After discharge from the hospital, the neonate should be followed by a pediatric endocrinologist who will monitor serum calcium levels, adjust medication dosage, and monitor growth and development. Certain neonates may require other subspecialty care based on associated medical issues.

Long-Term Outcome/Implications for Patient/Family

Transient hypocalcemia may resolve in a few days to weeks, and continued calcium supplementation is not required. Prolonged hypocalcemia will require long-term monitoring of serum calcium levels as the calcium requirements for infants change as they grow. Infants and children are at risk for hypocalcemia during illness, changes in certain medications (increase in loop diuretic therapy), or decreases in enteral intake, requiring close monitoring of calcium levels during these occasions. Infants with DiGeorge syndrome may have learning disabilities, cardiac disease, or poor growth because of feeding difficulties. These infants should be closely followed with individualized care with an emphasis on multidisciplinary care.

REFERENCES

INDICATION

Management of hyperkalemia involves treatment of elevated serum potassium levels in patients in the neonatal intensive care unit (NICU), particularly those dependent on parenteral fluids.

Clinical Findings

Initially, neonates should be in good fluid and electrolyte balance and thus have normal serum potassium concentrations. Exceptions can and do occur rarely but need to be recognized in a timely fashion.

1. Maternal history suggestive of abnormal fluid and electrolyte status

   1. Renal diseases with abnormal electrolytes

   2. Diuretic therapy

   3. Malnutrition or very abnormal diet

   4. Oligohydramnios

2. Physical findings suggestive of abnormal electrolyte balance

   1. Edema/anasarca

   2. Ascites, abdominal/flank masses

   3. Ambiguous genitalia

Confirmatory/Baseline Tests

The usual neonate, even the very premature patient, does not need serum electrolytes measured immediately after birth. Initially, a neonate’s electrolytes and creatinine should reflect the mother’s status. Patients with a history or physical findings like those mentioned in the discussion of clinical findings may need an electrolyte panel early in life. Note that in the face of normal placental and maternal renal function, a totally anephric neonate may have normal (ie, maternal) serum creatinine and potassium levels at birth.

1. Serum electrolytes should be followed closely in all low birth weight (LBW) and sick patients in the NICU. Serum potassium levels in neonates tend to be somewhat higher than in older children and adults and not uncommonly will be in the range of 5 to 6 mEq/L. However, levels greater than 6.5 should be watched closely, and those greater than 7 are associated with poor outcomes.

2. Hyperkalemia results in specific recognizable changes in the electrocardiogram (ECG) in the following progression:

   1. Tall, peaked T waves

   2. Prolonged P-R interval

   3. Widened QRS

   4. Bradycardia with abnormal QRS axis

   5. Ventricular fibrillation

Differential Diagnosis/Diagnostic Algorithm

Hyperkalemia in the neonate can be thought of in 4 categories:

1. Nonoliguric hyperkalemia (NOHK) occurs in the first few days of life in very low birth weight infants in the presence of normal urine output. It is caused by the transfer of potassium from the very high intracellular concentration (∼150 mEq/L) to the relatively low concentration in extracellular fluids. Factors that contribute to this potassium flux include

   1. Immaturity of the energy-dependant Na⁺-K⁺ ion pump, which may be worsened by perinatal hypoxia or hypoglycemia

   2. Acidosis resulting in increased H⁺-K⁺ exchange across cellular membranes

   3. Epidemiologic findings associated with NOHK, including

      • (1) Birth weight less than 1000 g

      • (2) Fetal distress

      • (3) Metabolic acidosis

      • (4) Hyperglycemia (caused by osmolality and low insulin)

      • (5) Polyuric renal failure

      • (6) No antenatal steroid treatment

   4. Tissue breakdown (eg, hemolysis, necrosis) is a minor contributor¹ to NOHK. Indeed, severe hemolytic disease of the newborn does not commonly result in life-threatening hyperkalemia. Rare situations exist in which tissue breakdown may result in hyperkalemia:

      • (1) Tumorlysis (eg, congenital leukemia)

      • (2) Rhabdomyolysis from trauma, commonly concomitant with oliguria

      • (3) Rapid massive hemolysis (eg, transfusion reaction)

2. Secondary to renal dysfunction: Decreased urine output can result in inappropriate potassium retention commonly seen with renal failure.

3. Secondary to endocrine dysfunction: Disordered renin-aldosterone-angiotensin system function can result in hyperkalemia with or without hyponatremia.

   1. Congenital adrenal hyperplasia (CAH)

   2. Pseudohypoaldosteronism

   3. Hyporeninemic hypoaldosteronism

   4. Massive adrenal hemorrhage

4. Iatrogenic

   1. Administration of too high an intravenous potassium load can overwhelm the limited excretory capabilities of the premature kidney and result in hyperkalemia; for this reason, no potassium is added to the initial intravenous fluids until good renal function and falling serum potassium concentrations are demonstrated.

   2. Factitious hyperkalemia is caused by leakage of intracellular potassium into serum samples during heel sticks.

   3. Drug-induced hyperkalemia can be caused by several drugs used in the NICU, most commonly the following:

      • (1) Spironolactone (impairs renal K⁺ excretion)

      • (2) Angiotensin-converting enzyme (ACE) inhibitors

      • (3) Nonsteroidal anti-inflammatory drugs (NSAIDS; eg, indomethacin, Ibuprofen)

      • (4) Calcium channel blockers

      • (5) β-Blockers

      • (6) Succinylcholine

      • (7) Digoxin

MANAGEMENT

Workup for Etiology of Hyperkalemia

1. Nonoliguric

   1. Rule out drug related

   2. Rule out factitious (particularly if heel stick sample)

   3. Rule out potassium overload: consider nonobvious source (eg, transfused old blood, medications)

   4. Rule out acidosis with arterial blood glass (ABG) examination

   5. Rule out hyperosmolality: electrolytes/glucose/osmolality

   6. Rule out polyuric renal failure: creatinine/serum urea nitrogen (BUN)

   7. History consistent with NOHK

2. Renal dysfunction: usually oliguric but may be polyuric

   1. Elevated creatinine/BUN

   2. Elevated fractional excretion of sodium (FeNa)

   3. Postobstructive diuresis, renal tubular acidosis, and so on

3. Endocrine: lack of aldosterone function in kidney

   1. CAH screen (hydrocortisone, 17-hydroxyProgesterone, etc)

   2. Hypoaldosteronism (aldosterone levels)

   3. Pseudohypoaldosteronism (renin, angiotensin)

Monitoring for Treatment

1. Intake and output (I&O) must be monitored strictly, especially in the smallest patients.

2. Weights should be charted no less than daily and may need to be checked more frequently in high-risk situations. For this, the use of bed scales may be beneficial.

3. Initial laboratory studies should include those for serum electrolytes, BUN/creatinine, calcium, and glucose, and an ABG to assess for acidosis. If there is acidosis, then blood gases will need to be followed, or at least serum electrolytes with bicarbonates, to monitor for metabolic acidosis.

4. Potassium, calcium, and glucose should be monitored closely, preferably with bedside “point-of-care” technology, to provide rapid data and minimize blood loss.

5. Continuous ECG monitoring with diagnostic capabilities to evaluate T waves, rate/rhythm, P-R interval, QRS, and so on should be initiated.

TREATMENT

Figure 73-1 indicates the steps in treatment.

1. Calcium: Calcium treats abnormal ECG (does not lower serum potassium). Note that hypocalcemia may be more common in neonates with NOHK² and should be corrected.

   1. Works on myocardial cells to improve membrane potential, but does not lower serum potassium

   2. Dose: 10% calcium gluconate 0.5 mL/kg IV over 5 minutes

2. A glucose/insulin infusion moves potassium from extra- to intracellular space with adenosine triphosphatase (ATPase) pump

   1. Start dextrose infusion first, at 0.5–1.0 g/kg/h, because this will increase endogenous insulin levels.

   2. Once glucose levels increase to over 150 mg/dL, initiate Insulin infusion at 0.1 U/kg/h and adjust per glucose levels.

3. Albuterol inhalation (0.4 mg/kg q 2h by nebulizer) may also be helpful in lowering serum potassium but is less effective than glucose/insulin.³ This also works via the ATPase pump. It must be used with care in patients with tachyarrhythmias.

4. Cation exchange resins have been used but appear to be less effective and have a significant risk of gastrointestinal injury (eg, perforation, necrotizing enterocolitis [NEC]).⁴ They bind about 0.5–1.0 mEq of potassium per gram of resin given.⁵

5. Infusions of saline (10 mL/kg) and furosemide (1 mg/kg) have not been proven effective in altering outcome but may lower serum potassium levels acutely.

6. Sodium bicarbonate (1 mEq/kg IV) increases pH and thus may increase potassium flux from extracellular to intracellular space. Although recommended in cases of acidosis, its efficacy for treating hyperkalemia has not been demonstrated.

FOLLOW-UP

After resolution of the acute hyperkalemic event, ongoing monitoring to detect any relapse is indicated. The type and frequency of monitoring vary with the etiology.

1. NOHK usually is self-limited to the first few days of life.

2. Renal dysfunction, depending on exact cause and severity, will need ongoing monitoring with nephrology and may need dialysis.

3. Endocrine causes such as CAH are usually ameliorated by proper hormonal manipulation.

4. Iatrogenic causes usually resolve once the cause is corrected.

Neurologic follow-up is indicated for neonates with marked hyperkalemia requiring treatment because this has been associated with neurologic injury.

1. Cranial sonography should be obtained once stable.

2. Follow-up in high-risk infants is recommended.

REFERENCES

INDICATION

This chapter outlines the treatment of low serum sodium levels in patients in the neonatal intensive care unit (NICU), particularly those dependent on parenteral fluids.

Epidemiology

The reported incidence of a serum sodium below 130 for very low birth weight infants in the NICU varies in the literature from about one-quarter to one-third.

Clinical Findings

Initially, neonates should be in good fluid and electrolyte balance and thus have normal serum sodium concentrations at birth. Exceptions can and do occur rarely but need to be recognized in a timely fashion.

1. Maternal history suggestive of abnormal fluid and electrolyte status

   1. Renal diseases with abnormal electrolytes

   2. Diuretic therapy

   3. Malnutrition or very abnormal diet

   4. Oligohydramnios

2. Physical findings suggestive of abnormal electrolyte balance

   1. Edema/anasarca

   2. Ascites, abdominal/flank masses

   3. Ambiguous genitalia

Laboratory

Usually, the neonate, even the very premature patient, does not need measurement of serum electrolytes immediately after birth. Initially, a neonate’s electrolytes and creatinine values should reflect the mother’s status. Patients with history or physical findings such as those mentioned may need to have an early evaluation of their electrolyte panel. Note that, in the face of normal placental and maternal renal function, a totally anephric neonate may have normal (ie, maternal) serum creatinine and sodium levels at birth.

1. Serum chemistries. These should be followed closely in all low birth weight (LBW) and sick patients in the NICU.

   1. Serum sodium levels in neonates tend to be somewhat lower than in older children and adults, and not uncommonly, they will be in the range of 130 to 140 mEq/L. However, levels less than 130 mEq/L should be watched closely, and levels less than 120 mEq/L are associated with poor outcomes.

   2. Serum potassium levels may be elevated in several conditions associated with hyponatremia (as discussed in the material that follows) and thus also should be followed.

   3. Serum urea and creatinine are markers for renal dysfunction and should be followed; again, they will be normal initially if placental and maternal renal functions are normal.

2. Urine chemistries. Urine sodium levels generally run below 30 mEq/L. We do not recommend routinely following urine chemistries, but they can be useful in determining the etiology of electrolyte abnormalities. Simultaneous urine creatinine determinations also can be useful for calculating the fractional excretion of sodium (FeNa) (see Figure 74-1).

3. Serum and urine osmolality.

4. Weights. Weights need to be checked daily at a minimum. Falling serum sodium with climbing weight suggests fluid retention; falling weight suggests sodium depletion.

Differential Diagnosis/Diagnostic Algorithm

Hyponatremia in the first days of life generally reflects only a few pathophysiologies:

1. Fluid (“free water”) overload. As discussed in Chapter 9, neonates are born with excess water that must be excreted. Because they are eunatremic at birth, this means that newborns also have a high total body sodium. However, the neonatal, particularly the premature, kidney has a limited ability to excrete a fluid load in the first few days of life. Thus, very early hyponatremia commonly is a problem of too much water and not too little sodium. Note that the chronic lack of thyroid hormone results in an inability to excrete a water load and thus can cause hyponatremia.

2. Increased sodium losses. Although unusual in the first few days, these can occur later in the NICU stay. Increased sodium losses can be caused by the following:

   1. Renal losses (eg, diuretic therapy)

   2. “Third-space” losses (eg, sepsis, necrotizing enterocolitis [NEC])

   3. Gastrointestinal losses (eg, emesis, large nasogastric tube drainage)

3. Renal salt wasting. Immature kidneys can have increased obligate sodium losses. A slow decrement in serum sodium over the first week of life in the presence of a normal sodium intake implies increased renal losses. Elevated urinary sodium levels can help confirm this diagnosis.

4. Secondary to renal failure. Decreased renal function can result in oliguria, inappropriate water retention, and decreased reabsorption of sodium. This can result in increased urine sodium losses and excess free water and thus hyponatremia.

5. Disordered renin-aldosterone-angiotensin system function. This can result in salt loss and hyperkalemia, such as from

   1. Congenital adrenal hyperplasia (CAH)

   2. Pseudohypoaldosteronism

   3. Hyporeninemic hypoaldosteronism

   4. Adrenal hemorrhage

   5. Hypertensive-hyponatremia syndrome. This is a rare complication of renovascular hypertension with natriuresis, hypovolemia, and secondary hyperaldosteronism.

6. Inadequate sodium intake. Over time, a low sodium intake can result in hyponatremia. It is important to note that human milk provides a relatively low-sodium diet. This rarely results in severe hyponatremia. Remember that salt depletion results in secondary volume depletion.

7. Factitious hyponatremia. This can be caused by other circulating osmoles (eg, hyperglycemia, contrast agents) or hyperlipidemia.

8. Drug-induced hyponatremia. Several drugs used in the NICU, most commonly diuretics such as furosemide or the combination of hydrochlorothiazide and spironolactone (“Aldactazide”), can result in hyponatremia.

9. Syndrome of inappropriate secretion of antidiuretic hormone (SIADH). This is somewhat unusual in a neonate but may be seen in the presence of raised intracranial pressure or in response to increased intrathoracic pressure.

   1. Nephrogenic SIADH has been described in neonates.

   2. Cerebral salt wasting (CSW). This is a poorly understood phenomenon of inappropriate salt and water loss after central nervous system (CNS) injury. Although hyponatremia with elevated urine osmolality may suggest SIADH, by definition CSW results in marked hypovolemia.

10. Hypothyroidism can impair water excretion and thus result in hyponatremia caused by fluid retention.

11. Glucocorticoid deficiency can impair water excretion and thus result in hyponatremia caused by fluid retention.

WORKUP FOR ETIOLOGY OF HYPONATREMIA

Figure 74-2 provides a 4-step algorithm for the workup for the etiology of hyponatremia.

Is It Real?

1. Rule out factitious hyponatremia (particularly if lab sample was drawn from vascular catheter).

2. Rule out hyperosmolality: Electrolytes/glucose/osmolality (eg, every 100 mg/dL increase in serum glucose decreases sodium by about 2.4 mEq/L).

3. Rule out diuretic induced hyponatremia.

Is It Renal Failure?

1. Creatinine/serum urea nitrogen (BUN) and FeNa are elevated (remember that diuretics will increase FeNa).

2. Renal failure usually is oliguric but may be polyuric.

3. If creatinine/BUN are normal but FeNa and urine sodium are elevated, look for causes of salt wasting (eg, renal salt wasting, CSW).

Is It Caused by Excess Free Water?

Neonates need to excrete significant water load in the first few days of life; too much fluid intake results in hypotonic fluid retention and either inadequate weight loss or even weight gain. These patients have no signs of hypovolemia.

1. FeNa and urine sodium are low: Edema is from exogenous fluid overload.

2. Urine osmolality and sodium are elevated: Consider causes of inadequate water diuresis (eg, SIADH, hypothyroidism, glucocorticoid deficiency).

Is It Caused by Low Total Body Sodium?

1. Sodium depletion results in secondary hypovolemia.

2. Excess weight loss, oliguria, and low blood pressure follow.

3. FeNa and urine sodium are low, but the creatinine/BUN may be slightly elevated because of hemoconcentration.

4. Serum potassium concentration usually is normal.

If Hyperkalemic

If hyperkalemia is present, consider renal-aldosterone dysfunction.

1. CAH screen (hydrocortisone, 17-hydroxyprogesterone, etc)

2. Hypoaldosteronism (aldosterone levels)

3. Pseudohypoaldosteronism (renin, angiotensin)

Monitoring for Treatment

1. Intake and output (I&O) must be monitored strictly, especially in the smallest patients.

2. Weights should be charted no less than daily and may need to be checked more frequently in high-risk situations. For this, the use of bed scales may be beneficial.

3. Electrolytes, BUN, and creatinine values should be monitored closely, preferably with bedside “point-of-care” technology to provide rapid data and minimize blood loss.

TREATMENT

Fluid Restriction

Decreasing free water intake by approximately 20% will start correcting hyponatremia caused by excess free water that results from either administration of too much fluid or inappropriate water retention (ie, SIADH).

Normal Saline

Normal saline (NS) (0.9%; 154 mEq/L) is usually infused as the first and safest step for replenishing a sodium deficit. An intravenous bolus of NS, 10 mL/kg, will restore both sodium and volume losses and improve hyponatremia caused by hypovolemia or increased sodium losses in the presence of appropriate levels of antidiuretic hormone (ADH); it will not help SIADH.

Hypertonic Saline

Hypertonic saline (3%; 513 mEq/L) is used for severe hyponatremia (sodium < 120 mEq/L) to correct to a target serum sodium of 125 mEq/L over about 12 hours, then correct the rest of the deficit over the next 24 hours (see Figure 74-2 for calculation). The rate of correction should not exceed 0.5 mEq/L per hour.

FOLLOW-UP

1. After resolution of the acute hyponatremic event, ongoing monitoring to detect any relapse is indicated. The type and frequency of monitoring vary with the etiology.

2. Iatrogenic fluid overload should not recur once recognized and appropriate fluid restriction is initiated.

3. Inadequate sodium intake needs to be followed with both serum and urine sodium levels to ensure that sodium intake is greater than ongoing urinary losses.

4. Renal dysfunction, depending on exact cause and severity, will need ongoing monitoring with nephrology and may need dialysis.

5. Endocrine causes such as CAH are usually ameliorated by proper hormonal manipulation but require close follow-up.

6. Neurologic follow-up is indicated for neonates with marked hyponatremia requiring treatment because this has been associated with neurologic injury and hearing loss.

   1. Cranial sonography should be obtained once stable.

   2. Audiology screening should be done prior to discharge.

   3. Follow-up in the high-risk infant is recommended.

SUGGESTED READING

BACKGROUND

Serum glucose levels (GLU) in the fetus are dependent on transplacental transfer of glucose from the mother and generally reflect maternal levels. Elevated maternal GLU can cause fetal hyperglycemia and increased insulin production by the fetal pancreas, resulting in fetal macrosomia. After separation from the placenta, newborn infants have to maintain their own GLU without maternal assistance. Thus, although usually euglycemic, the newborn could be either hyperglycemic or hypoglycemic depending on the maternal serum glucose and the infant’s ability for endocrine autoregulation.

EPIDEMIOLOGY

The exact incidence of transient neonatal hypoglycemia is unknown. Studies using continuous glucose monitoring have suggested that it is more common than previously believed, but the significance of this finding in asymptomatic, otherwise-well babies is unclear. Specific subgroups of neonates have been identified as having significantly increased risk of developing hypoglycemia:

• Small-for-gestational-age (SGA) infants

• Large-for-gestational-age (LGA) infants

• Infant of diabetic mother (IDM)

• Infant of gestational diabetic mother (IGDM)

• Septic infants

• Late preterm infants (LPTIs) born at 34⁺⁰ to 36⁺⁶ weeks’ gestation

• Postdate infants

CLINICAL FINDINGS

1. Maternal history suggestive of abnormal glucose status

   Diabetes mellitus

   Obesity

   Intravenous glucose administration

   Abnormal fetal growth

   Placental abnormalities (eg, too large/small, abruption)

   Fetal intolerance of labor (eg, abnormal tracing, meconium staining)

2. Neonatal findings suggestive of abnormal glucose homeostasis

   Intrauterine growth restriction/SGA

   Macrosomia/LGA

   Jitteriness

   Seizures

   Lethargy/poor feeding

   Apnea

   Unremarkable examination

LABORATORY WORKUP

Screening is recommended as follows only for at-risk infants:

1. IDM and LGA infants: screen for first 24 hours

2. LPTIs and SGA infants: screen for first 12 hours

3. Continue screening hypoglycemic infants until maintaining preprandial GLU 45 mg/dL or more for 2–3 feeding intervals

The definition of neonatal hypoglycemia has been debated, but most recently, the American Academy of Pediatrics (AAP) has defined it as follows:

• GLU less than 40 mg/dL and symptomatic

• GLU less than 25 mg/dL from birth to 4 hours of age after initial feeding

• GLU less than 35 mg/dL prior to subsequent feeding from 4 to 24 hours of age

A simplified algorithm for screening is shown in Figure 75-1.

TREATMENT

Enteral

Initial treatment is by enteral nutrition whenever possible if the baby is asymptomatic. See Figure 75-1 for a simplified treatment algorithm for asymptomatic neonates.

Glucose Infusion

If the baby is symptomatic or the GLU remains below 25 mg/dL when checked 1 hour after feeding, then intravenous treatment is needed:

1. Minibolus of 200 mg/kg dextrose (eg, 2 mL/kg of 10% dextrose in water [D10W]), followed by intravenous infusion.

2. Dextrose intravenously at about 5–8 mg/kg per minute (approximately 80–130 mL/kg daily of D10W) adjusted to keep GLU in the range of 40 to 60 mg/dL.

3. Avoid hyperglycemia, which can lead to increased insulin secretion, thus exacerbating the problem.

Once the GLU has stabilized in the appropriate range, the intravenous D10W can be weaned slowly by decreasing the rate by small increments every other feeding while continuing to feed and following GLU prefeeding.

If the patient does not maintain GLU of 45 mg/dL or greater after treatment as outlined or does not tolerate attempts to wean the rate of intravenous D10W, then proceed to work up for persistent hyperglycemia, beginning with obtaining critical laboratory values (see Chapter 105).

FOLLOW-UP

Continue to monitor GLU for screening interval described in Figure 75-1 and previously this chapter.

Symptomatic infants are at significant risk of neurologic injury and may be considered for magnetic resonance imaging (MRI) before discharge. They should be followed closely for evidence of developmental delay.

Asymptomatic infants with easily controlled transient hypoglycemia do not require neuroimaging or special developmental follow-up.

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