1979, British Journal of Radiology, 52, 410-411
Case reports Pulmonary oedema following intravenous urography in a neonate By W. H. McAlister, M.D., Marilyn J. Siegel, M.D. and G. D. Shackelford, M.D. Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110 (Received August, 1978 and in revisedform November, 1978)
The quantity of contrast agent that should be used for intravenous urography for neonates has been consistently higher than that for older children and adults. The authors wish to report an 18-day-old girl who developed pulmonary oedema shortly after receiving 4.7 ml/kg of Hypaque 50, a dose within the range recommended in some publications (Henderson and Torch, 1977; Standen et aL, 1965).
oxygen, semi-erect position, and intravenous digitalization. A chest roentgenogram 20 minutes following injection of the contrast agent confirmed pulmonary oedema (Fig. 1B). An abdominal roentgenogram several hours later showed normal kidneys. A chest roentgenogram the following day showed virtually complete clearing of the pulmonary oedema. The patient continued to do well, and clinical and laboratory cardiac evaluation were normal. Subsequent intravenous urography has been performed without difficulty.
CASE HISTORY
The type of adverse response in our patient suggests overdosage by a hypertonic contrast medium with resultant cardiopulmonary failure from increased intravascular volume. Previous investigators (Bernstein et aL, 1961; Busfield et aL, 1962; Lachlan, 1970; Lindgren et aL, 1968; Mudd et aL, 1965; Sotos et aL, 1962; Standen et aL, 1965) have
DISCUSSION
A 3 kg newborn girl who was the product of an uneventful pregnancy and delivery, was admitted to St. Louis Childdren's Hospital for exstrophy of the bladder, imperforate anus, and a small omphalocele. The omphalocele was repaired the first day of life and a colostomy performed. A chest roentgenogram demonstrated only slight dextroversion of the heart (Fig. 1A). She was clinically stable and well hydrated without unusual fluid loss from the colostomy. On day 17 the patient's serum chloride, sodium, potassium and blood urea nitrogen were normal. On day 18 the patient had an unprepared intravenous urogram. Fourteen ml (4.7 ml/ kg) of Hypaque 50 (sodium diatrizoate) was injected through a 23 gauge needle. The length of time of injection was under one minute. A few minutes following the injection, the patient became cyanotic, and had bloody frothy sputum, tachycardia and tachypnoea. Auscultation revealed bilateral rales and rhonchi. The clinical diagnosis was pulmonary oedema, and the patient was treated with
B
1. Chest roentgenograms showing (A) slight dextrorotation of the heart with normal lungs and (B) acute pulmonary oedema following intravenous urography. 410 FIG.
MAY
1979
Case reports shown profound rapid changes in patients and experimental animals in serum osmolarity, pH, electrocardiography, heart rate and blood pressure, following the injection of urographic agents or hypertonic agents. A coincidental fall in haematocrit in experimental animals also occurs, indicating that fluid was being rapidly drawn into the vascular compartment. Fatal cardiopulmonary reactions in infants and children have been reported with overdoses in the range of 7 to 9 ml/kg or greater. One was a newborn infant (weight 2.1 kg at the time of urography) who died of cardiopulmonary failure soon after receiving 7.0 ml/kg of Conray 60 (meglumine iothalamate) (McClennan et al, 1972). Ansell (1970) reported three other infants dying from overdoses of intravenous contrast agents. The amount of urographic agent received in these three patients was (1) 250 ml of 30% Urografin (80 ml/kg) meglumine and sodium diatrizoate; (2) 25 ml of Urovison (8 ml/kg) (meglumine and sodium diatrizoate); and (3) 20 ml of Urografin (6 ml/kg) repeated after ten minutes. A 3.7 kg infant developed reversible cardiac arrest and pulmonary oedema after receiving 3.3 ml/kg of 45% sodium diatrizoate (Ansell, 1976). Pulmonary oedema has been reported in adults receiving contrast media (Malins, 1978; Shehadi, 1975). Deaths in experimental animals from the commonly used monomeric intravenous contrast agents (Hypaque 50, Conray 60, and Renografin 60) has been reported with doses ranging from 6.8-19 ml/kg and higher (Bernstein et al, 1961; Busfield et al., 1962; McClennan et al, 1972; Salvesen, 1973). The wide range of toxicity values in experimental animals largely reflects differences in rates of injection of the contrast agents (Busfield et al., 1962; Hoppe, 1959; Salvesen, 1973). Busfield et al. (1962) in their experiments on rats almost doubled the LD50 levels by slow injections. In newborn rats the LD50 of Hypaque 50 is 10 ml/kg, one half that of the adult rat (Kaufman et ah, 1966). The LD50 of dogs receiving Hypaque M90 rapidly injected was 3 ml/ kg and death resulted from pulmonary oedema (Bernstein e* al, 1961). Several authors recommended 5 ml/kg of contrast agent for newborns (Henderson and Torch, 1977; Standen et al, 1965). However, in view of our case of a newborn developing frank congestive failure and pulmonary oedema from slightly less than 5 ml/kg we recommend that the dose be no greater than 4 ml/kg. Since another neonate developed pulmonary oedema with 3.3 ml/kg perhaps the figure should be less than 3 ml/kg. Higher doses should be injected slowly. There should be
valid indications for intravenous urography in small infants, especially those under 2 kg, because of thermal instability and the rapid changes in serum osmolarity. There are no good prospective studies on optimal intravenous urography dosage in neonates. The current recommendations are empirical. Investigations performed on adults and experimental animals suggest that dosages greater than 2 ml/kg for the usual contrast agents (Conray 60, Hypaque 50, Renografin 60) do not improve urography (McClennan et al, 1971). However, this may not be valid for neonates. REFERENCES ANSELL, G., 1970. Fatal overdose of contrast medium in infants. British Journal of Radiology, 43, 395-396. 1976. Complications in Diagnostic Radiology, p. 22 (Blackwell Scientific Publications, Oxford). BERNSTEIN, E. F., PALMER, J. D., AABERG, T. A., and DAVIS,
R. L., 1961. Studies of the toxicity of Hypaque-90%, following rapid intravenous injection. Radiology, 76, 88-95. BUSFIELD, D., CHILD, K. J., and TOMICH, E. G., 1962.
Pharmacological and toxicological studies on Triosil, an intravenous contrast agent. British Journal of Radiology, .35,815-823. HENDERSON, K. C , and TORCH, E. M., 1977. Differential
diagnosis of abdominal masses in the neonate. Pediatric Clinics of North America, 24, 557-578. HOPPE, J. O., 1959. Some pharmacological aspects of radiopaque compounds. Annals of the New York Academy of Sciences, 78, 727-739. KAUFMAN, H. J., PROBST, H., BREITENSTEIN, R., and OBER-
HOLTZER, R., 1966. The testing of the LD50 for angiographic contrast media in the neonatal rat. Annals de
Radiologie, 9,Z\\-2\6.
LACHLAN, H., 1970. Biochemical and other changes occurring in infants during angiocardiography. Proceedings of the Royal Society of Medicine, 63, 46-48. LINDGREN, P., SALTZMAN, G.-F., and TORNELL, G., 1968.
Vascular reaction of water-soluble contrast media. Acta Radiologica, Diagnosis, 7, 152-160. MCCLENNAN, B. L., BECKER, J. A., and BREDON, W. E.,
1971. Excretory urography. Choice of contrast material— experimental. Radiology, 100, 585-590. MCCLENNAN, B. L., KASSNER, E. G., and BECKER, J. S.,
1972. Overdose at excretory urography: toxic cause of death. Radiology, 105, 383-386. MALINS, A. F., 1978. Pulmonary oedema after radiologic investigations of peripheral occlusive vascular disease adverse reaction to contrast media. Lancet, 1, 413-415. MUDD, J. G., AYKENT, Y., and DESCHRIJVER, C , 1965.
Hemodynamic, pathologic and cinegraphic effects of contrast media on the pulmonary vasculature. Diseases of the Chest, 48, 55-63. SALVESEN, S., 1973. Acute toxicity tests of metrizamide. Acta Radiologica; Supplement, 335, 5-13. SHEHADI, W. H., 1975. Adverse reactions to intravascularly administered contrast media. Americal Journal of Roentgenology, 124, 145-152. SOTOTS, J. F., DODGE, P. R., and TALBOT, N. B., 1962.
Studies in experimental hypertonicity II. Hypertonicity of body fluids as a cause of acidosis. Pediatrics, 30, 180-193. STANDEN, J. R., NOGRADY, M. B., DUNBAR, J. S., and
411
GOLDBLOOM, R. B., 1965. The osmotic effects of methylglucamine diatrizoate (Renografin 60) in intravenous urography in infants. American Journal of Roentgenology, 93, 473 -479.
Case reports Pulmonary oedema following intravenous urography in a neonate By W. H. McAlister, M.D., Marilyn J. Siegel, M.D. and G. D. Shackelford, M.D. Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110 (Received August, 1978 and in revisedform November, 1978)
The quantity of contrast agent that should be used for intravenous urography for neonates has been consistently higher than that for older children and adults. The authors wish to report an 18-day-old girl who developed pulmonary oedema shortly after receiving 4.7 ml/kg of Hypaque 50, a dose within the range recommended in some publications (Henderson and Torch, 1977; Standen et aL, 1965).
oxygen, semi-erect position, and intravenous digitalization. A chest roentgenogram 20 minutes following injection of the contrast agent confirmed pulmonary oedema (Fig. 1B). An abdominal roentgenogram several hours later showed normal kidneys. A chest roentgenogram the following day showed virtually complete clearing of the pulmonary oedema. The patient continued to do well, and clinical and laboratory cardiac evaluation were normal. Subsequent intravenous urography has been performed without difficulty.
CASE HISTORY
The type of adverse response in our patient suggests overdosage by a hypertonic contrast medium with resultant cardiopulmonary failure from increased intravascular volume. Previous investigators (Bernstein et aL, 1961; Busfield et aL, 1962; Lachlan, 1970; Lindgren et aL, 1968; Mudd et aL, 1965; Sotos et aL, 1962; Standen et aL, 1965) have
DISCUSSION
A 3 kg newborn girl who was the product of an uneventful pregnancy and delivery, was admitted to St. Louis Childdren's Hospital for exstrophy of the bladder, imperforate anus, and a small omphalocele. The omphalocele was repaired the first day of life and a colostomy performed. A chest roentgenogram demonstrated only slight dextroversion of the heart (Fig. 1A). She was clinically stable and well hydrated without unusual fluid loss from the colostomy. On day 17 the patient's serum chloride, sodium, potassium and blood urea nitrogen were normal. On day 18 the patient had an unprepared intravenous urogram. Fourteen ml (4.7 ml/ kg) of Hypaque 50 (sodium diatrizoate) was injected through a 23 gauge needle. The length of time of injection was under one minute. A few minutes following the injection, the patient became cyanotic, and had bloody frothy sputum, tachycardia and tachypnoea. Auscultation revealed bilateral rales and rhonchi. The clinical diagnosis was pulmonary oedema, and the patient was treated with
B
1. Chest roentgenograms showing (A) slight dextrorotation of the heart with normal lungs and (B) acute pulmonary oedema following intravenous urography. 410 FIG.
MAY
1979
Case reports shown profound rapid changes in patients and experimental animals in serum osmolarity, pH, electrocardiography, heart rate and blood pressure, following the injection of urographic agents or hypertonic agents. A coincidental fall in haematocrit in experimental animals also occurs, indicating that fluid was being rapidly drawn into the vascular compartment. Fatal cardiopulmonary reactions in infants and children have been reported with overdoses in the range of 7 to 9 ml/kg or greater. One was a newborn infant (weight 2.1 kg at the time of urography) who died of cardiopulmonary failure soon after receiving 7.0 ml/kg of Conray 60 (meglumine iothalamate) (McClennan et al, 1972). Ansell (1970) reported three other infants dying from overdoses of intravenous contrast agents. The amount of urographic agent received in these three patients was (1) 250 ml of 30% Urografin (80 ml/kg) meglumine and sodium diatrizoate; (2) 25 ml of Urovison (8 ml/kg) (meglumine and sodium diatrizoate); and (3) 20 ml of Urografin (6 ml/kg) repeated after ten minutes. A 3.7 kg infant developed reversible cardiac arrest and pulmonary oedema after receiving 3.3 ml/kg of 45% sodium diatrizoate (Ansell, 1976). Pulmonary oedema has been reported in adults receiving contrast media (Malins, 1978; Shehadi, 1975). Deaths in experimental animals from the commonly used monomeric intravenous contrast agents (Hypaque 50, Conray 60, and Renografin 60) has been reported with doses ranging from 6.8-19 ml/kg and higher (Bernstein et al, 1961; Busfield et al., 1962; McClennan et al, 1972; Salvesen, 1973). The wide range of toxicity values in experimental animals largely reflects differences in rates of injection of the contrast agents (Busfield et al., 1962; Hoppe, 1959; Salvesen, 1973). Busfield et al. (1962) in their experiments on rats almost doubled the LD50 levels by slow injections. In newborn rats the LD50 of Hypaque 50 is 10 ml/kg, one half that of the adult rat (Kaufman et ah, 1966). The LD50 of dogs receiving Hypaque M90 rapidly injected was 3 ml/ kg and death resulted from pulmonary oedema (Bernstein e* al, 1961). Several authors recommended 5 ml/kg of contrast agent for newborns (Henderson and Torch, 1977; Standen et al, 1965). However, in view of our case of a newborn developing frank congestive failure and pulmonary oedema from slightly less than 5 ml/kg we recommend that the dose be no greater than 4 ml/kg. Since another neonate developed pulmonary oedema with 3.3 ml/kg perhaps the figure should be less than 3 ml/kg. Higher doses should be injected slowly. There should be
valid indications for intravenous urography in small infants, especially those under 2 kg, because of thermal instability and the rapid changes in serum osmolarity. There are no good prospective studies on optimal intravenous urography dosage in neonates. The current recommendations are empirical. Investigations performed on adults and experimental animals suggest that dosages greater than 2 ml/kg for the usual contrast agents (Conray 60, Hypaque 50, Renografin 60) do not improve urography (McClennan et al, 1971). However, this may not be valid for neonates. REFERENCES ANSELL, G., 1970. Fatal overdose of contrast medium in infants. British Journal of Radiology, 43, 395-396. 1976. Complications in Diagnostic Radiology, p. 22 (Blackwell Scientific Publications, Oxford). BERNSTEIN, E. F., PALMER, J. D., AABERG, T. A., and DAVIS,
R. L., 1961. Studies of the toxicity of Hypaque-90%, following rapid intravenous injection. Radiology, 76, 88-95. BUSFIELD, D., CHILD, K. J., and TOMICH, E. G., 1962.
Pharmacological and toxicological studies on Triosil, an intravenous contrast agent. British Journal of Radiology, .35,815-823. HENDERSON, K. C , and TORCH, E. M., 1977. Differential
diagnosis of abdominal masses in the neonate. Pediatric Clinics of North America, 24, 557-578. HOPPE, J. O., 1959. Some pharmacological aspects of radiopaque compounds. Annals of the New York Academy of Sciences, 78, 727-739. KAUFMAN, H. J., PROBST, H., BREITENSTEIN, R., and OBER-
HOLTZER, R., 1966. The testing of the LD50 for angiographic contrast media in the neonatal rat. Annals de
Radiologie, 9,Z\\-2\6.
LACHLAN, H., 1970. Biochemical and other changes occurring in infants during angiocardiography. Proceedings of the Royal Society of Medicine, 63, 46-48. LINDGREN, P., SALTZMAN, G.-F., and TORNELL, G., 1968.
Vascular reaction of water-soluble contrast media. Acta Radiologica, Diagnosis, 7, 152-160. MCCLENNAN, B. L., BECKER, J. A., and BREDON, W. E.,
1971. Excretory urography. Choice of contrast material— experimental. Radiology, 100, 585-590. MCCLENNAN, B. L., KASSNER, E. G., and BECKER, J. S.,
1972. Overdose at excretory urography: toxic cause of death. Radiology, 105, 383-386. MALINS, A. F., 1978. Pulmonary oedema after radiologic investigations of peripheral occlusive vascular disease adverse reaction to contrast media. Lancet, 1, 413-415. MUDD, J. G., AYKENT, Y., and DESCHRIJVER, C , 1965.
Hemodynamic, pathologic and cinegraphic effects of contrast media on the pulmonary vasculature. Diseases of the Chest, 48, 55-63. SALVESEN, S., 1973. Acute toxicity tests of metrizamide. Acta Radiologica; Supplement, 335, 5-13. SHEHADI, W. H., 1975. Adverse reactions to intravascularly administered contrast media. Americal Journal of Roentgenology, 124, 145-152. SOTOTS, J. F., DODGE, P. R., and TALBOT, N. B., 1962.
Studies in experimental hypertonicity II. Hypertonicity of body fluids as a cause of acidosis. Pediatrics, 30, 180-193. STANDEN, J. R., NOGRADY, M. B., DUNBAR, J. S., and
411
GOLDBLOOM, R. B., 1965. The osmotic effects of methylglucamine diatrizoate (Renografin 60) in intravenous urography in infants. American Journal of Roentgenology, 93, 473 -479.
