A 3-week-old female neonate was brought into the emergency department by paramedics late one evening. Her mother had been awakened by noises that the neonate was making and found the child gasping and stiff. The mother called 911. When the paramedics arrived, the mother told them that the neonate had been well when she was put to bed that night, but had taken only approximately half of her usual amount of feedings. Her intake had decreased from 3 to VA ounces every 3 hours. Fever had not been noted at home and there were no complaints of rhinorrhea, cough, vomiting, or diarrhea. Her mother was the primary caregiver and no one was ill in her home.
The neonate had been delivered vaginally at 40 weeks' gestation to a 17-year-old primiparous woman. She was discharged home after 3 days to reside with her mother and her great-aunt. There were no complications reported during pregnancy or delivery, or postnatally. Specifically, her mother denied infections such as herpes, gonorrhea, chlamydia, or human immunodeficiency virus. The neonate had received her first hepatitis B vaccination. She was not taking any medications, nor was she allergic to any medications. There was no family history of childhood illnesses.
On physical examination, the neonate appeared ill and was difficult to console. She had a rectal temperature of 38.8°C, a heart rate of 180 beats per minute, a respiratory rate of 68 breaths per minute, and a blood pressure of 50/24 mm Hg. Her pulse oximetry was 98% in room air. Her anterior fontanelle was open and slightly sunken. Her pupils were equal and reactive from 4 to 2 mm bilaterally. Her extraocular muscles were intact and red reflexes were present bilaterally. Her tympanic membranes were normal. Although her mucous membranes were dry, no intraoral lesions were appreciated.
The neonate was tachypneic with mild intercostal retractions and abdominal breathing, but her lungs were clear on auscultation, without wheezing or crackles. Aside from tachycardia, results of the cardiac examination were normal. Perfusion was compromised with prolonged (3second) capillary refill and weak pulses. The abdomen was soft with active bowel sounds. The liver was felt 1 cm below the right costal margin with a normal span of 6 cm and there was no splenomegaly. Her genitalia and extremities were normal. There was no rash. The neurologic examination revealed an irritable, hypotonic neonate with 1+ deep tendon reflexes. Her cranial nerves were intact. She had intact Moro, grasp, and fencing reflexes.
This neonate presented with fever and irritability, chief complaints frequently encountered in the emergency department. Our initial diagnosis included infection from a bacterial etiology such as bacteremia, meningitis, urinary tract infection, or pneumonia. Most physicians would probably agree that a "sepsis" workup was in order. This includes blood, urine, and cerebrospinal fluid cultures and a chest radiograph. A complete blood cell count, urinalysis, electrolytes, and serum glucose were also obtained. Empiric antimicrobial coverage was initiated to cover the most common etiologic organisms for the patient's age (group B streptococcus, Escherichia coli, Listeria monocytogenes, and herpes simplex virus).
In this case, a sepsis workup was performed, but the lumbar puncture was deferred secondary to the severity of the patient's illness. Antimicrobial coverage was begun with ampicillin, cefotaxime, and acyclovir. A 20-mL/kg bolus of normal saline was given and arrangements were made to transfer the neonate to a local children's hospital.
Shortly after the sepsis evaluation, the neonate began to have seizures consisting of facial twitching and rhythmic jerking of the extiemities with intermittent episodes of apnea that required bag valve mask ventilation. She was initially given 0.1 mg /kg of intravenous lorazepam. After 5 minutes of continued seizure activity, she was given a second dose but continued to have seizure activity resistant to benzodiazepines. She began to have worsening periods of apnea with pulse oximetry desaturations to 70%. Airway control was obtained with endotracheal intubation after rapid sequence induction. This is a technique used to rapidly deliver adequate muscle relaxation and sedation to facilitate the intubation and minimize possible complications. The neonate was also given 20 mg /kg of phénobarbital. The seizure activity stopped.
The etiologies of neonatal seizures are different from the etiologies of seizures in infants and children. The most common causes of neonatal seizures include central nervous system infections, hypoxic-ischemic encephalopathy, hypoglycemia, intracranial hemorrhage, a structural anomaly in the brain, and drug withdrawal.1 After witnessing seizure activity, we began to narrow our initial diagnosis. The probable diagnosis at this point was either bacterial meningitis or viral encephalitis, such as herpes.
Subsequently, laboratory results were obtained. Serum sodium was 193 mmol/L, potassium 4.3 mmol/L, chloride 114 mmol/L, bicarbonate 40 mmol/L, blood urea nitrogen 19 mg/dL, creatinine 1.1 mg/dL, glucose 231 mg/dL, and calcium 6.3 mg/dL. Her complete blood cell count revealed a white blood cell count of 15,000 /mL, hemoglobin of 12 g/dL, hematocrit of 37.5%, and platelets of 484,000 /mL. The manual differential had 44% segmented neutrophils, 41% lymphocytes, and 13% monocytes.
When the transport team arrived, the neonate began to have intermittent seizures again. Calcium gluconate was given. The neonate was also given 20 mg /kg of phenytoin. She was brought to the pediatric intensive care unit for further treatment and stabilization. On arrival to the regional children's hospital, she had received three 20-mL/kg boluses of normal saline; two 100-mg/kg boluses of calcium gluconate; lorazepam; phenobarbital; and phenytoin.
Because the most striking abnormality in this neonate was her dramatic hypernatremia, it was prudent to start the differential diagnosis with causes of hypernatremia to assist in providing a unifying diagnosis. Hypernatremia is defined as a serum sodium level greater than 150 mEq/L. Levels greater than 160 mEq/L are considered critical.2 The body has several mechanisms to regulate the concentration of serum sodium between 135 and 145 mg/dL. Important components of this regulatory mechanism include antidiuretic hormone to increase reabsorption of water in the kidneys and idiogenic osmole production in the brain to increase intracellular osmolality.3 It is thought that the brain cells produce idiogenic osmoles to counterbalance long-term elevations of the extracellular osmolality. The components of these idiogenic osmoles include myo-inositol, sorbitol, betaine, glutamine, glutamate, taurine, and other substances to raise the intracellular osmolality of the brain cells.3
The differential diagnosis for hypernatremia (Table) can be broken down into three main etiologies: hypotonic fluid losses, excess sodium, or water deficit.2 Typically, hypernatremia results from a water imbalance rather than a sodium overload.
Hypotonic fluid loss is the most common etiology of hypernatremia. It may be seen with viral gastroenteritis in the United States and cholera in developing countries. Sodium is lost in hypematremic dehydration secondary to gastroenteritis. but there is a greater free water loss that leads to the hypernatremia.2 Although our patient had a febrile illness, there was no history of diarrhea to explain her fever and hypernatremia.
Hypernatremia due to excess sodium is rare. However, there are several case reports of sodium poisoning in infants.4"6 Typically, these children have been administered some form of sodium (eg, salt or baking soda). Iatrogenic causes such as improper formula preparation, sodium poisoning, or administration of bicarbonate during resuscitation should be investigated.
Water deficit, the third main etiology, tends to occur in those whose access to water is restricted in some way. This typically includes young children who cannot access water, those who are bedridden, or those with increased insensible losses through the skin or lungs with inadequate replacement. Water deficit is a particular problem for individuals with central or nephrogenic diabetes insipidus. Hypernatremia results from a decrease in total body water greater man the decrease in total body sodium. Although our patient had decreased oral intake, her access to fluids was not restricted in any way.
The clinical presentation of the patient with hypernatremic dehydration is early neurologic irritability with a relative preservation of the circulatory status.7 That is, the heart rate and blood pressure do not accurately reflect the actual degree of total body water deficit. Because the patient is hypernatremic, the dehydration is more intracellular than extracellular, and the circulatory status is relatively preserved. However, there are early neurologic symptoms due to the intracellular dehydration within the brain. The cerebral dehydration causes the brain to shrink away from the skull and pull on the bridging veins, leading to intracranial hemorrhages.2 Patients with hypernatremic dehydration are irritable, lethargic, and often febrile. Coma and seizures may develop. Our patient had the classic appearance of an irritable septic neonate who had early neurologic signs and symptoms of greater magnitude than cardiovascular instability, which is consistent with hypernatremia.
Associated laboratory abnormalities include hyperglycemia and hypocalcemia. However, the mechanism is unclear. Our patient was both hyperglycemic and hypocalcémie. Hypernatremic metabolic acidosis is seen in patients with gastroenteritis, whereas hypernatremic metabolic alkalosis is seen with the adniinistration of sodium bicarbonate.
Differential Diagnosis of Hypernatremia
In the pediatric intensive care unit, there was time to obtain a more detailed history. It was discovered that the mother had been adding baking soda to the neonate's formula for the past week to relieve perceived abdominal pain. She added 4 tablespoons of baking soda to a gallon of water, boiled the baking soda-water combination, and then mixed it 1:1 with the formula. This addition of sodium bicarbonate to the formula gave an extra 643 mEq of sodium to every gallon of water used to mix with the formula. Standard formula has 70.8 mEq of sodium per liter; this formula preparation had 240.9 mEq of sodium per liter. By comparison, ocean water has 480 mEq of sodium per liter.
The final diagnosis was hypernatremia due to sodium bicarbonate poisoning that resulted in seizures and fever.
SUMMARY OF THE CUNlCAL COURSE
The initial treatment of this neonate centered on slowly lowering her serum sodium, maintaining her hemodynamic status with pressor support, correcting associated electrolyte abnormalities, and adrrunistering anticonvulsant therapy. The therapeutic goal was to lower the serum sodium by 0.5 mEq /L per hour. The slow correction of hypernatremia will help to prevent cerebral edema. The free water deficit was replaced during a period of 48 hours. The free water deficit can be calculated as 4 mL/kg for every milliequivalent per liter the serum sodium is greater than 145.8 The patient was also given maintenance fluids, and replacement of ongoing losses was provided. If a patient is hyperglycemic, the glucose concentration of the intravenous fluids can be reduced to 2.5% dextrose. Insulin should be avoided because rapid reduction of hyperglycemia may be associated with cerebral edema.7 Calcium gluconate can be given if the serum calcium is low. Potassium will assist water entry into the cell.9
The outcome from hypernatremia is variable. There is at least a 10% mortality rate.4 The degree of neurologic recovery is not well correlated with the severity of the hypernatremia or the acute neurologic changes accompanying the hypernatremia.4 However, the development of new neurologic deficits is greater when the serum sodium level is greater than 160 mEq/ L.10
The results of our patient's initial electroencephalogram were positive for seizure activity. A magnetic resonance imaging study of her brain revealed bilateral parietal infarcts, right temporal infarct, and bilateral choroid plexus hemorrhages. She passed her brain stem audiometry evoked response, but failed her visual evoked response and was thought to be cortically blind. Approximately 72 hours after her initial presentation, her serum sodium level returned to 145 mEq/L. Cultures of blood, urine, and cerebrospinal fluid were all negative.
This case teaches many lessons. First, it is of paramount importance to get an accurate and thorough history. Questioning the initial diagnosis is always prudent, particularly when there are deviations from the typical presentation, such as marked irritability, episodes of apnea, and seizures that are difficult to manage. The neuroradiographic findings in patients with hypernatremia have been confused with nonacddental trauma, furthering the need for a thorough history, physical examination, and laboratory assessment.11
Second, metabolic disorders should be considered when patients have recalcitrant seizures that are not responsive to traditional therapy. This is especially true for children in the first year of life.
Finally, prevention of iatrogenic hypernatremia is crucial. Subsequent to a similar case, Arm and Hammer changed the warning label on Arm and Hammer Baking Soda on December 10, 1990.4 The first warning listed is not to use baking soda for children younger than 5 years.
1. Tunnessen WW. Seizures. In: Tunnessen WW, Roberts KB, eds. Signs and Symptoms in Pediatrics, 3rd ed. Philadelphia: Lippincott Williams & Wilkins; 1999:713-717.
2. Conley SB. Hypernatremia. Pediatr Clin North Am. 1990; 37:365-372.
3. lien YH, Shapiro JL Chan L. Effects of hypernatremia on organic brain osmoles. J Clin Invest. 199035:1427-1435.
4. Nichols MH, Wason S, Gonzalez del Rey J, Benfield M. Baking soda: a potentially fatal home remedy. Pediatr Emerg Care. 1995;11:109-111.
5. Yercen N, Caglayan S, Yucel N, Yaprak I, Ogun A, Unver A. Fatal hypernatremia in an infant due to salting of the skin. Am J Dis Child. 1993;147:716-717.
6. Fuchs S, Listernick R Hypernatremia and metabolic alkalosis as a consequence of the therapeutic misuse of baking soda. Pediatr Emerg Care. 1987;3:242-243.
7. Finberg L. Hypernatremic (hypertonic) dehydration in infants. N Engl J Med. 1973;289:196-198.
8. Cronan K, Norman ME. Renal and electrolyte emergencies. In: Fleisher GR, Ludwig S, eds. Textbook of Pediatric Emergency Medicine, 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2000:817.
9. Finberg L. Therapeutic management of hypernatremic dehydration. In: Finberg L, Kravath RE, Hellerstein S, eds. Wafer and Electrolytes in Pediatrics: Physiology, Pathophysiology, and Treatment, 2nd ed. Philadelphia: W. B. Saunders; 1993:149.
10. Macaulay D, Watson M. Hypernatremia in infants as a cause of brain damage. Arch Dis Child. 1967;42:485-491.
11. Mocharla R, Schexnayder SM, Glasier CM. Fatal cerebral edema and intracranial hemorrhage associated with hypernatremic dehydration. Pediatr Radiol. 1997;27:785-787.
Differential Diagnosis of Hypernatremia