Acute
Phosphate Intoxication in Seven Infants Under Parenteral Nutrition D.
From Free
BIARENT, MD; C. BRUMAGNE, MD;
University of Brussels,
Intensive Care Unit for
M.
STEPPE, MD;
AND
J.-M. BOUTON, MD
Children, Hôpital Universitaire des Enfants, Reine Fabiola, Brussels, Belgium
ABSTRACT. After major surgery, seven infants aged 4 to 29 weeks, under parenteral nutrition, received monosodium phosphate (4.2 to 14.3 mEq/kg body weight) instead of prescribed calcium gluconate. The wrong solution was perfused during 16 hours. At the 15th hour, blood samples showed hyperphosphatemia in all (8.0 to 14.4 mg/100 mL) and hypocalcemia in four infants (6.1 to 8.0 mg/100 mL), but all were asymptomatic. a perfusion of glucose in water, calcemia and phosphatemia returned to normal within 24 hours. In a review of the
Under
The known causes of hyperphosphatemia are overloads of
endogenous (cellular lysis) or exogenous (intoxica-2 tions) origin and an elimination default (renal failure).1> The symptoms of an acute hyperphosphatemia are lethargy up to coma, tachypnea, tetany, and bradycardia up to cardiac arrest. Soft-tissue calcification is likely to in some cases. The severity of the symptoms is linked to the severity of the hypocalcemia, but the phosphatemia (P04) plays a role in determining the vital occur
prognosis.
pediatric literature, we found 11 subjects with symptomatic acute phosphate intoxication, who also presented with hypocalcemia and hyperphosphatemia. The differences were that they received high bolus doses of phosphate orally or rectally and showed symptomatic features. Normalization of the calcemia occurred only when hyperphosphatemia was corrected throughout intravenous hydration. (Journal of Parenteral and Enteral Nutrition 16 :558-560, 1992)
(Table I). Calcium and phosphate measured on blood drawn at the 15th hour of infusion (H-1) showed hyperphosphatemia in all infants and hypocalcemia in four infants with phosphatemia of 9.9 mg/100 mL or greater (AC, DK, KR, and MC in Table I). The blood ions were monitored until normalization. No significant change was observed for sodium, potassium, or bicarbonate. P04 levels decreased quickly and were normal 11 hours after the end of the infusion (Hll) in all but one infant with
We report seven accidental intravenous phosphate intoxications in infants. Although severe intoxications with rectal or oral phosphate solution are well documented in children, we found no pediatric report of intravenous intoxication. Concentrations in plasma phosphate (elemental phosphor) and calcium are expressed as milligrams per 100 mL of plasma.
slight preexistent renal insufficiency due to nephrocalcinosis. In this last infant, the phosphaturia was still high 24 hours after the end of infusion (47 mg/kg per 24 hours), whereas it was already normal in the four other patients in whom we could obtain the phosphaturia (between 0.5 and 7.6 mg/kg per 24 hours). For all the subjects, before any calcium administration, the calcemia was normalized in a short period of time, ie, within 24 hours. It was closely related to the rate of normalization of the hyperphosphatemia (Fig. 1). In all infants, an CASE REPORT echography of the kidneys was performed during the first Seven infants, aged 4 to 29 weeks (mean: 15 weeks), 48 hours following the intoxication. A second ultrasound weighing 2.3 to 6.2 kg (mean: 4.1 kg), on parenteral evaluation was performed after 1 to 4 months. No echonutrition for major digestive or cardiac surgery were graphic calcium phosphate deposits were observed during prescribed 2 mEq calcium/kg body weight (calcium glu- this follow-up period. conate diluted in a volume of 4 mL). The hospital pharmacy accidentally delivered 4 mL of monosodium phosphate, corresponding to 12 mEq P04/kg body weight, DISCUSSION instead of calcium. As soon as the error was brought to our attention (after 16 hours of infusion We surveyed the pediatric literature since 1970 and HO), parenteral nutrition was replaced by 10% glucose in water. found three cases of oral’-’ and eight cases of enema Although the received amount was between 4.2 and phosphate intoxicationss-12 (Table II). Symptoms at ad14.3 mEq/kg in 16 hours, no child was symptomatic mission suggested the diagnosis in all cases. In most, the amount of incriminated phosphate was grossly evaluated (between 11 and 180 mEq/kg). Some of the children with previous abnormal digestive mucosa or presented Reprint requests: Dr D. Biarent, Hôpital Universitaire des Enfants, Reine Fabiola, 15 J-J Crocq, B-1020 Brussels, Belgium. renal insufficiency responsible for an enhanced absorp=
av
558 Downloaded from pen.sagepub.com at UNIVERSITY OF SASKATCHEWAN LIBRARY on March 17, 2015
559 TABLE I Patients’ blood ualues
PN prescribed parenteral nutrition; P04 phosphoremia; Ca Calcemia; Prot Proteinemia; Creat Creatininemia; Ca x P04 product; H-1 15th hour after the beginning of incriminated PN; H23 23 hours after PN was replaced by glucose infusion. =
=
=
=
=
=
=
solubility
=
TABLE II Cited
cases
of enema phosphate intoxication
FIG. 1. Evolution of the blood values. H-1 15th hour since beginning of incriminated parenteral nutrition. HO interruption of incriminated parenteral nutrition.
.
=
=
-,-
-...--..-
FIG. 2. Review of the literature: Evolution of calcium and P04 in blood since the time of poisoning.
Downloaded from pen.sagepub.com at UNIVERSITY OF SASKATCHEWAN LIBRARY on March 17, 2015
560 or a poor excretion of the drug. Thirty to 65% of the administered phosphate was probably really absorbed.6.8& The treatment consisted of ionic rehydration with calcium. One child died 12 and one developed severe neurologic sequelae9; both patients presented with severe ionic disorders. In all cases, calcemia began to rise only when the levels of P04 came down, despite intravenous calcium administration since the beginning of symptoms’ (Fig.
tion
2).
infants, the overload was large but gradual and perfused in a solution containing glucose without any calcium. Only the four infants with the highest phosphatemia had hypocalcemia (Table I). The rate of P04 intoxication, whether or not the compensatory mechanisms have the time to initiate, plays a role in the importance of hypocalcemia.’ Hyperphosphatemia induces hypocalcemia through calcium phosphate fixation and decreases renal synthesis of 1,25(OH)2 D vitamin. Extra skeletal calcifications may appear when the calcium and P04 concentration product In
P04
our
was
exceeds 70.~’~ Calcium should be administered only to alleviate the clinical symptoms due to hypocalcemia and not in an attempt to normalize the plasma calcium level. Indeed, the risk of phosphocalcic precipitation exists until the P04 is below the critical level. Insulin and glucose enhance entry of P04 into the cells. In the kidney, the reabsorption of P04 is lowered by the serum glucose&dquo; and the parathyroid hormone level, which enhance the urinary excretion.1, 14 An infusion of glucose (with insulin, if necessary, and potassium because of the increased risk of hypokalemia) facilitates renal excretion of the phosphates and seems to be the most effective treatment of hyperphosphatemia due to P04 intoxication.
ACKNOWLEDGMENT
We thank Professor H.-L. Vis for his support.
REFERENCES
K, Levine BS, Lee DBN, et al: Physiology of phosphorus metabolism and pathophysiology of hypophosphatemia and hyperphosphatemia. IN Fluid Electrolyte and Acid-Base Disorders, Vol 1, Arieff AI, De Fronzo RA (eds). Churchill Livingstone, New York, 1985, pp 625-658 2. Peppers MP, Geheb M, Desai T: Hypophosphatemia and hyperphosphatemia. Crit Care Clin 7:201-214, 1991 3. Levitt M, Gessert C, Finberg L: Inorganic phosphate (laxative) poisoning resulting in tetany in an infant. J Pediatr 82:479-481, 1973 4. Smith MS, Feldman KW, Furukawa CT: Coma in an infant due to hypertonic sodium phosphate medication. J Pediatr 82:481-482, 1973 5. Geffner ME, Opas LM: Phosphate poisoning complicating treatment for iron ingestion. Am J Dis Child 134:509-510, 1980 6. Chesney RW, Haughton PB: Tetany following phosphate enemas in chronic renal disease. Am J Dis Child 127:584-586, 1974 7. Oxnard SC, O’Bell J, Grupe WE: Severe tetany in an azotemic child related to a sodium phosphate enema. Pediatrics 55:105-106, 1974 8. Davis RF, Eichner JM, Bleyer A, Okamoto G: Hypocalcemia, hyperphosphatemia and dehydration following a single hypertonic phosphate enema. J Pediatr 90:484-485, 1977 9. Loughnan P, Mullins GC: Brain damage following a hypertonic phosphate enema. Am J Dis Child 131:1032, 1977 10. Sotos JF, Cutler EA, Doody D: Hypocalcemic coma following two pediatric phosphate enemas. Pediatrics 60:305-307, 1977 11. Wason S, Tiller T, Cunha C: Severe hyperphosphatemia, hypocalcemia acidosis and shock in a 5-month-old child following the administration of an adult Fleet enema. Ann Emerg Med 18:6961. Kurokawa
700, 1989 RR, Lisehora GR, Braxton M, et al: Fatal poisoning from sodium phosphate enema. JAMA 257:2190-2192, 1987 13. Herbert LA, Lemann J, Petersen JR, et al: Studies of mechanisms
12. Martin
by which phosphate infusion lowers
serum calcium concentration. J Clin Invest 45:1886-1894, 1966 14. Corman B, Touvay C, Poujeol P, et al: Glucose-mediated inhibition of phosphate reabsorption in rat kidney. Am J Physiol 235:F430-
F439, 1978
Downloaded from pen.sagepub.com at UNIVERSITY OF SASKATCHEWAN LIBRARY on March 17, 2015
Phosphate Intoxication in Seven Infants Under Parenteral Nutrition D.
From Free
BIARENT, MD; C. BRUMAGNE, MD;
University of Brussels,
Intensive Care Unit for
M.
STEPPE, MD;
AND
J.-M. BOUTON, MD
Children, Hôpital Universitaire des Enfants, Reine Fabiola, Brussels, Belgium
ABSTRACT. After major surgery, seven infants aged 4 to 29 weeks, under parenteral nutrition, received monosodium phosphate (4.2 to 14.3 mEq/kg body weight) instead of prescribed calcium gluconate. The wrong solution was perfused during 16 hours. At the 15th hour, blood samples showed hyperphosphatemia in all (8.0 to 14.4 mg/100 mL) and hypocalcemia in four infants (6.1 to 8.0 mg/100 mL), but all were asymptomatic. a perfusion of glucose in water, calcemia and phosphatemia returned to normal within 24 hours. In a review of the
Under
The known causes of hyperphosphatemia are overloads of
endogenous (cellular lysis) or exogenous (intoxica-2 tions) origin and an elimination default (renal failure).1> The symptoms of an acute hyperphosphatemia are lethargy up to coma, tachypnea, tetany, and bradycardia up to cardiac arrest. Soft-tissue calcification is likely to in some cases. The severity of the symptoms is linked to the severity of the hypocalcemia, but the phosphatemia (P04) plays a role in determining the vital occur
prognosis.
pediatric literature, we found 11 subjects with symptomatic acute phosphate intoxication, who also presented with hypocalcemia and hyperphosphatemia. The differences were that they received high bolus doses of phosphate orally or rectally and showed symptomatic features. Normalization of the calcemia occurred only when hyperphosphatemia was corrected throughout intravenous hydration. (Journal of Parenteral and Enteral Nutrition 16 :558-560, 1992)
(Table I). Calcium and phosphate measured on blood drawn at the 15th hour of infusion (H-1) showed hyperphosphatemia in all infants and hypocalcemia in four infants with phosphatemia of 9.9 mg/100 mL or greater (AC, DK, KR, and MC in Table I). The blood ions were monitored until normalization. No significant change was observed for sodium, potassium, or bicarbonate. P04 levels decreased quickly and were normal 11 hours after the end of the infusion (Hll) in all but one infant with
We report seven accidental intravenous phosphate intoxications in infants. Although severe intoxications with rectal or oral phosphate solution are well documented in children, we found no pediatric report of intravenous intoxication. Concentrations in plasma phosphate (elemental phosphor) and calcium are expressed as milligrams per 100 mL of plasma.
slight preexistent renal insufficiency due to nephrocalcinosis. In this last infant, the phosphaturia was still high 24 hours after the end of infusion (47 mg/kg per 24 hours), whereas it was already normal in the four other patients in whom we could obtain the phosphaturia (between 0.5 and 7.6 mg/kg per 24 hours). For all the subjects, before any calcium administration, the calcemia was normalized in a short period of time, ie, within 24 hours. It was closely related to the rate of normalization of the hyperphosphatemia (Fig. 1). In all infants, an CASE REPORT echography of the kidneys was performed during the first Seven infants, aged 4 to 29 weeks (mean: 15 weeks), 48 hours following the intoxication. A second ultrasound weighing 2.3 to 6.2 kg (mean: 4.1 kg), on parenteral evaluation was performed after 1 to 4 months. No echonutrition for major digestive or cardiac surgery were graphic calcium phosphate deposits were observed during prescribed 2 mEq calcium/kg body weight (calcium glu- this follow-up period. conate diluted in a volume of 4 mL). The hospital pharmacy accidentally delivered 4 mL of monosodium phosphate, corresponding to 12 mEq P04/kg body weight, DISCUSSION instead of calcium. As soon as the error was brought to our attention (after 16 hours of infusion We surveyed the pediatric literature since 1970 and HO), parenteral nutrition was replaced by 10% glucose in water. found three cases of oral’-’ and eight cases of enema Although the received amount was between 4.2 and phosphate intoxicationss-12 (Table II). Symptoms at ad14.3 mEq/kg in 16 hours, no child was symptomatic mission suggested the diagnosis in all cases. In most, the amount of incriminated phosphate was grossly evaluated (between 11 and 180 mEq/kg). Some of the children with previous abnormal digestive mucosa or presented Reprint requests: Dr D. Biarent, Hôpital Universitaire des Enfants, Reine Fabiola, 15 J-J Crocq, B-1020 Brussels, Belgium. renal insufficiency responsible for an enhanced absorp=
av
558 Downloaded from pen.sagepub.com at UNIVERSITY OF SASKATCHEWAN LIBRARY on March 17, 2015
559 TABLE I Patients’ blood ualues
PN prescribed parenteral nutrition; P04 phosphoremia; Ca Calcemia; Prot Proteinemia; Creat Creatininemia; Ca x P04 product; H-1 15th hour after the beginning of incriminated PN; H23 23 hours after PN was replaced by glucose infusion. =
=
=
=
=
=
=
solubility
=
TABLE II Cited
cases
of enema phosphate intoxication
FIG. 1. Evolution of the blood values. H-1 15th hour since beginning of incriminated parenteral nutrition. HO interruption of incriminated parenteral nutrition.
.
=
=
-,-
-...--..-
FIG. 2. Review of the literature: Evolution of calcium and P04 in blood since the time of poisoning.
Downloaded from pen.sagepub.com at UNIVERSITY OF SASKATCHEWAN LIBRARY on March 17, 2015
560 or a poor excretion of the drug. Thirty to 65% of the administered phosphate was probably really absorbed.6.8& The treatment consisted of ionic rehydration with calcium. One child died 12 and one developed severe neurologic sequelae9; both patients presented with severe ionic disorders. In all cases, calcemia began to rise only when the levels of P04 came down, despite intravenous calcium administration since the beginning of symptoms’ (Fig.
tion
2).
infants, the overload was large but gradual and perfused in a solution containing glucose without any calcium. Only the four infants with the highest phosphatemia had hypocalcemia (Table I). The rate of P04 intoxication, whether or not the compensatory mechanisms have the time to initiate, plays a role in the importance of hypocalcemia.’ Hyperphosphatemia induces hypocalcemia through calcium phosphate fixation and decreases renal synthesis of 1,25(OH)2 D vitamin. Extra skeletal calcifications may appear when the calcium and P04 concentration product In
P04
our
was
exceeds 70.~’~ Calcium should be administered only to alleviate the clinical symptoms due to hypocalcemia and not in an attempt to normalize the plasma calcium level. Indeed, the risk of phosphocalcic precipitation exists until the P04 is below the critical level. Insulin and glucose enhance entry of P04 into the cells. In the kidney, the reabsorption of P04 is lowered by the serum glucose&dquo; and the parathyroid hormone level, which enhance the urinary excretion.1, 14 An infusion of glucose (with insulin, if necessary, and potassium because of the increased risk of hypokalemia) facilitates renal excretion of the phosphates and seems to be the most effective treatment of hyperphosphatemia due to P04 intoxication.
ACKNOWLEDGMENT
We thank Professor H.-L. Vis for his support.
REFERENCES
K, Levine BS, Lee DBN, et al: Physiology of phosphorus metabolism and pathophysiology of hypophosphatemia and hyperphosphatemia. IN Fluid Electrolyte and Acid-Base Disorders, Vol 1, Arieff AI, De Fronzo RA (eds). Churchill Livingstone, New York, 1985, pp 625-658 2. Peppers MP, Geheb M, Desai T: Hypophosphatemia and hyperphosphatemia. Crit Care Clin 7:201-214, 1991 3. Levitt M, Gessert C, Finberg L: Inorganic phosphate (laxative) poisoning resulting in tetany in an infant. J Pediatr 82:479-481, 1973 4. Smith MS, Feldman KW, Furukawa CT: Coma in an infant due to hypertonic sodium phosphate medication. J Pediatr 82:481-482, 1973 5. Geffner ME, Opas LM: Phosphate poisoning complicating treatment for iron ingestion. Am J Dis Child 134:509-510, 1980 6. Chesney RW, Haughton PB: Tetany following phosphate enemas in chronic renal disease. Am J Dis Child 127:584-586, 1974 7. Oxnard SC, O’Bell J, Grupe WE: Severe tetany in an azotemic child related to a sodium phosphate enema. Pediatrics 55:105-106, 1974 8. Davis RF, Eichner JM, Bleyer A, Okamoto G: Hypocalcemia, hyperphosphatemia and dehydration following a single hypertonic phosphate enema. J Pediatr 90:484-485, 1977 9. Loughnan P, Mullins GC: Brain damage following a hypertonic phosphate enema. Am J Dis Child 131:1032, 1977 10. Sotos JF, Cutler EA, Doody D: Hypocalcemic coma following two pediatric phosphate enemas. Pediatrics 60:305-307, 1977 11. Wason S, Tiller T, Cunha C: Severe hyperphosphatemia, hypocalcemia acidosis and shock in a 5-month-old child following the administration of an adult Fleet enema. Ann Emerg Med 18:6961. Kurokawa
700, 1989 RR, Lisehora GR, Braxton M, et al: Fatal poisoning from sodium phosphate enema. JAMA 257:2190-2192, 1987 13. Herbert LA, Lemann J, Petersen JR, et al: Studies of mechanisms
12. Martin
by which phosphate infusion lowers
serum calcium concentration. J Clin Invest 45:1886-1894, 1966 14. Corman B, Touvay C, Poujeol P, et al: Glucose-mediated inhibition of phosphate reabsorption in rat kidney. Am J Physiol 235:F430-
F439, 1978
Downloaded from pen.sagepub.com at UNIVERSITY OF SASKATCHEWAN LIBRARY on March 17, 2015
