PEDIATRICS Vol. 118 No. 5 November 2006, pp. e1580-e1583 (doi:10.1542/10.1542/peds.2006-1249)
EXPERIENCE & REASON |
Severe Hyperphosphatemia and Hypocalcemic Tetany After Oral Laxative Administration in a 3-Month-Old Infant
a Divisions of Pediatric Critical Care
c Pediatric Nephrology
b Department of Pediatrics, Harbor-UCLA Medical Center, Los Angeles, California
d Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, California
ABSTRACT
A 3-month-old infant presented to the pediatric emergency department with respiratory distress and tetany after ingestion of a phosphate-containing oral laxative. The initial phosphorus level was 38.3 mg/dL. With aggressive fluid resuscitation and intravenous calcium administration, the infant completely recovered. Although the risks of phosphate-containing enemas are well described, life-threatening hyperphosphatemia can also result from administration of phosphate-containing oral laxatives. Aggressive fluid hydration is the mainstay of treatment. Intravenous calcium administration may be necessary to avoid hemodynamic collapse despite the theoretical possibility of metastatic calcifications. Physicians should be alerted to the possibility of phosphate toxicity and hypocalcemic tetany in young children when treated with over-the-counter laxatives. Caregivers should be advised not to administer over-the-counter laxatives to infants without physician supervision.
Key Words: hyperphosphatemia • hypocalcemia • laxative • phosphate toxicity • tetany • anion gap
Phosphate toxicity from administration of sodium-phosphate enemas is well recognized. Although enemas are available over-the-counter, multiple reports of phosphate toxicity have alerted practitioners to use these preparations with caution. Over-the-counter laxatives may also contain large amounts of phosphate; however, the perception of most caregivers is that these are safe and nontoxic. Phosphate toxicity from oral laxative ingestion in a patient with no underlying renal or gastrointestinal abnormality is rarely reported and has been reported only once for a child.1 Here we present a case of severe hyperphosphatemia and hypocalcemic tetany in a 3-month-old infant after administration of an oral laxative and review treatment options.
CASE REPORT
A previously healthy 3-month-old, 4.5-kg black boy was referred to the emergency department by his primary care doctor for respiratory distress and fever. His parents stated that the child had been irritable, breathing fast, and febrile for the previous 24 hours. In the emergency department, significant physical examination findings included a heart rate of 203 beats per minute, moderate-to-severe respiratory distress with respirations of 70 per minute, blood pressure of 100/73 mm Hg, a rectal temperature of 40.2°C, and lethargy. Oxygen saturations were initially 80% on room air but increased to 100% with supplemental oxygen. The infant was also noted to have intermittent muscular spasms and stiffness of all 4 extremities. These abnormal movements were interpreted as possible seizure activity.
Initial treatment included administration of normal saline, antibiotics, and antipyretics. Cultures of blood, urine, and cerebral spinal fluid were obtained. Results of a computed tomography scan of the head, performed because of the lethargy and abnormal movements, were negative.
Laboratory data (detailed in Table 1) revealed a sodium level of 155 mEq/L, creatinine level of 0.9 mg/dL (reference range: 0.2–0.4 mg/dL), calcium level of 5.1 mg/dL (reference range: 8.5–11.0 mg/dL), phosphorus level of 38.3 mg/dL (reference range: 3.2–6.3 mg/dL), and an anion gap of 29 mmol/L. Intravenous calcium gluconate was administered, and the patient was transferred to the PICU for continued evaluation and treatment.
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In the PICU, the patient continued to be tachycardic and tachypneic, with moderate-to-severe respiratory distress. An ionized calcium level on arrival to the PICU was 2.3 mg/dL (reference range: 4.6–5.3 mg/dL). The abnormal muscular spasms and stiffness were thought to be tetany. Initial electrocardiographic rhythm strips revealed sinus tachycardia, a prolonged QTc, and u waves. Calcium chloride was administered intravenously over 15 minutes with rapid cessation of generalized muscular stiffness and marked resolution of respiratory distress.
Additional interventions included administration of additional calcium, aggressive fluid hydration, and placement of a central venous catheter (see Table 1). Approximately 4 hours after initial presentation, the infant's phosphorus level had decreased to 28.2 mg/dL. A calcium-chloride infusion was started at 5 mg/kg per hour but was discontinued 4 hours later when the ionized calcium level reached 3.3 mg/dL.
Pediatric nephrology was consulted. Results of a renal ultrasound, performed to ascertain if there was any preexisting renal disease, were normal. Additional laboratory tests revealed an elevated parathyroid hormone level of 153 pg/mL (reference range: 10–61 pg/mL), lactic acid level of 1.4 mmol/L (reference range: 0.3–2.6 mmol/L), normal complete blood cell count, normal thyroid-function tests, and a salicylate level of <40 µg/mL.
During the first day of hospitalization, urine output was maintained over 2 mL/kg per hour, and the electrolytes normalized. It is notable that the phosphorus level rapidly declined to reference values within 20 hours of initial presentation. The infant completely recovered with no residual deficits and was discharged from the PICU on hospital day 3. All cultures were negative.
After additional questioning, the parents admitted that they were concerned the infant was "constipated" but denied administration of phosphate-containing enemas. However, they had been treating the infant with peppermint herb tea (8 oz/day), simethicone drops, slivers of Ivory soap administered rectally, and an over-the-counter phosphate-containing laxative, Purgasol (DLC Marketing Company, Paramount, CA). During the preceding 7 days, 2 mL of Purgasol was given every 4 hours with each feed.
DISCUSSION
Life-threatening and even fatal hyperphosphatemia has been reported after excessive exogenous phosphate administration.1–5 The consequences of hyperphosphatemia are related to its effect on lowering serum calcium. In addition to tetany, seizures, coma, and respiratory distress, hypocalcemia can have profound hemodynamic consequences including arrhythmias. The patient described here displayed several of these clinical features, including electrocardiographic changes.
Common causes of hyperphosphatemia include impaired renal function, tissue necrosis, rhabdomyolysis, tumor lysis syndrome, and exogenous administration. Moseley and Segar6 published the first report of exogenous phosphate toxicity in children in 1968. They reported 4 children with Hirschsprung disease who were given hypertonic phosphate enemas. Treatment consisted mainly of intravenous fluids and calcium, and all the children survived. Although phosphate toxicity from rectal enema preparations is well described,7–10 toxicity from oral laxatives is not commonly reported. The extremely elevated phosphate level in our patient is consistent with acute exogenous toxicity rather than a chronic process. The highest phosphate level reported in children with acute toxicity is 63.3 mg/dL, in contrast to those seen with chronic conditions in whom the phosphate levels are generally only twice the reference value.2
Without preexisting renal or gastrointestinal disease, serious phosphate toxicity is rarely reported. Despite no previous renal or gastrointestinal dysfunction, the infant described here developed phosphate toxicity as a result of the extremely large amount of phosphate he ingested. Purgasol contains 2.4 g of monobasic sodium phosphate (NaH2PO4) and 0.9 g of dibasic sodium phosphate (Na2HPO4) per 5 mL. With conversion to millimoles, the patient received 
63 mmol/day (13 mmol/kg per day) of phosphate for 7 days, which is markedly greater than the recommended daily allowance for this infant (3.2 mmol of phosphate per day).11 Although the lethal dose of phosphate in humans is unknown, Martin et al2 reported that the lethal dose of phosphate in pigs is 35 mmol/kg.
Essential to the treatment of phosphate toxicity is increasing urinary excretion, because phosphate balance is maintained predominately by renal excretion. The glomerulus filters 85% of circulating phosphate, and the proximal tubule actively resorbs 80% of filtered phosphate.12 Increased parathyroid hormone levels and expansion of the extracellular space with saline have both been shown to increase renal phosphate excretion.6,12 Therefore, aggressive hydration is the mainstay of treatment, guided by urine output and, if necessary, measurement of central venous pressure.
The intestines absorb 65% of dietary phosphate,9,13 but when gut motility is impaired, absorption is enhanced. Phosphate binders (such as aluminum hydroxide and sevelamer hydrochloride) are antacids that bind to phosphate and render it nonabsorbable. Inhibition of intestinal phosphate absorption with phosphate binders has proven effective in lowering serum phosphorus levels over several days, especially in the setting of chronic renal failure. The effectiveness of these medications in the acute setting is unknown. We chose not to administer a phosphate binder because the phosphorus level rapidly decreased with hydration and the patient was not receiving oral feeds.
Dialysis is commonly used in patients with renal failure and hyperphosphatemia. Hemodialysis can clear phosphate at a significantly higher rate than that achieved by normal kidneys. The indication for dialysis in acute exogenous phosphate administration is generally oliguria or anuria rather than the absolute phosphate level.8 Monitoring urine output and the rate of serum phosphorus reduction is critical in evaluating the need for this therapy.
Another important component in the treatment of hyperphosphatemia is the management of the resultant hypocalcemia. Administration of intravenous calcium is somewhat controversial because of the possibility of metastatic calcifications when the calcium-phosphate concentration product is >70 mg2/dL2.14 Although this complication has been described in a number of disease states, especially chronic renal failure, nephrocalcinosis from isolated acute hyperphosphatemia has never been confirmed by renal biopsy.9,10 Autopsies of humans and animals with acute hyperphosphatemia have not demonstrated calcium-phosphate deposition in the kidneys.15–17 Perlman4 described a 2-month-old former 28 weeks' gestation premature infant who inadvertently received 30 times the normal dose of oral phosphate. The physicians were reluctant to administer calcium secondary to concern for renal precipitation, although marked hypocalcemia (ionized calcium: 2.9 mg/dL) was present. Despite treatment with intravenous fluids, an oral phosphate binder and, eventually, an exchange transfusion, the infant developed an acute arrhythmia and subsequently died. Their case emphasizes that despite the theoretical possibility of metastatic calcifications, it seems prudent to administer sufficient calcium to correct potentially lethal cardiac complications.
Selection of the particular calcium salt used for treatment of hypocalcemia, calcium chloride or calcium gluconate, should be considered. Broner et al18 demonstrated that intravenous administration of calcium chloride increased ionized calcium levels greater than an equivalent dose of calcium gluconate. Adverse effects from extravasation of calcium salts into subcutaneous tissue are well known.19 Accordingly, the risks and benefits of infusing calcium salts through a peripheral versus central line should be assessed carefully.
Our patient also presented with an elevated anion gap metabolic acidosis. Although frequently underrecognized, hyperphosphatemia is one of the many causes of increased anion gap. Under normal circumstances, the contribution of serum phosphate to anion gap is minimal, because each 3.5 mg/dL of phosphate contributes only 2 mmol/L to anion gap. In this case, however, the serum phosphate of 38.3 mg/dL was responsible for 21.9 mmol/L of the total anion gap of 29 mmol/L. As the serum phosphate declined with treatment, the anion gap normalized.
CONCLUSIONS
Life-threatening hyperphosphatemia can result from administration of exogenous phosphate in previously healthy children. Over-the-counter oral laxatives may contain large amounts of phosphate and should be given with extreme caution because the resultant hypocalcemia can have devastating clinical consequences. In patients with phosphate toxicity, intravenous hydration should be the first line of treatment. Oral phosphate binders can be considered but are likely of minimal benefit in the fasting patient. Dialysis should be implemented in the patient with renal dysfunction; however, dialysis may be unnecessary in patients with good urine output and a rapidly declining phosphorus level. Intravenous calcium should be administered to correct any cardiac abnormalities, especially dysrhythmias. Pediatricians should routinely advise caregivers not to give over-the-counter oral laxatives to infants and young children without previous consultation.
FOOTNOTES
Accepted Jun 7, 2006.
Address correspondence to Richard Mink, MD, Division of Pediatric Critical Care, Harbor-UCLA Medical Center, 1000 W, Carson St, Box 491, Torrance, CA 90509. E-mail: rmink{at}ucla.edu
The authors have indicated they have no financial relationships relevant to this article to disclose.
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PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics
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