Brief clinical and laboratory observations
Volume 93 Number 6
5.
6.
7.
8.
9. 10.
I I.
12. 13.
14.
tion of function oflymphocytes, Clin Exp Immunol13: 171, 1973. Schellekens PThA, and Eijsvoogel VP: Lymphocyte transformation in vitro: IV. Recruitment in antigen-stimulated cullures, Clin Exp ImmunoI8:187, 1971. Hopkinson DA, Cook PS, and Harris H : Further data on the adenosine deaminase (ADA) polymorphism and a report of a new phenotype, Ann Hum Genet 32:361, 1969. Battistuzzi G, Scozzari R, Santolamazza P, Terrentano L, and Modiano G: Comparative activity of red cell adenosine dearninase allelic forms, Nature 251:7II, 1974. Weening RS, Roos D, and Loos JA: Oxygen consumption of phagocytizing cells in human leukocyte and granulocyte preparations. A comparative study, J Lab Clin Med 83:570, 1974. Solberg CO: Protection of phagocytized bacteria against antibiotics, Acta Med Scand 191:383, 1972. Astaldi A, Astaldi OCB, Wijermans P, Groenewoud M, Schellekens PTbA, and Eijsvoogel VP: Thymosin-induced human serum factor increasing cyclic AMP, J Immunol 119: 1106, 1977. Zigmond SH, and Hirsch JG : Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor, J Exp Med 137:387, 1973. Worthington Enzyme Manual, Freehold, N.J., 1972, Worthington Biochemical Corp., p 100. Goldste in 1M, Roos D, Kaplan HB, and Weissmann G: Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis, J Clin Invest 56: 1155, 1975. Zuelzer WW, Mastrangelo R, Stulberg CS, Poulik HD, Page RH, and Thompson RI: Autoimmune hemolytic anemia. Natural history and Viral-immunologic interactions in childhood, Am J Med 48:80, 1970.
1003
15. Smith SD, Cho CT, Brahmacupta N, and Lenahan MF: Pulmonary involvement with cytomegalovirus infections in children, Arch Dis Child 52:441, 1977. 16. Sandman R, Ammann AJ, Grose C, and Wara DW: Cellular immunodeficiency associated with nucleoside phosphorylase deficiency. Immunologic and biochemical studies, Clin Imrnunol Immunopathol 8:247, 1977. 17. Borgers M, Verhaegen H, De Brabander M, Thoue F, van Reernpts J, and Genens G: Purine nucleoside phosphorylase, a possible histochemical marker for T-cells in man, J Immunol Methods 16:IOJ, 1977. 18. Groslong T, Horowitz S, Lovchik J, Davis A, and Hong R: Chronic cytomegalovirus infection and immunodeficiency: Antigen-driven malignancy? J PEDIATR 88:217, 1976. 19. Polmar SH, Stern RC, Schwartz AL, Wetzler EM, Chase PA, and Hirschhorn R : Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immune deficiency, N Engl J Med 295:1337, 1976. 20. Zegers BIM, Stoop JW , Hendrickx OFM, Wadman SK, and Staal GEl: Purine nucleoside phosphorylase deficiency associated with cellular immunodeficiency: immunologicaL follow-up during treatment, Proceedings of the Symposium of the Society for the Study of Inborn Errors in Man, New York, Academic Press, Inc (in press). 21. Wright DO, Kirkpatrick CH, and Gallin Jl: Effects of levarnisole on normal and abnormal leukocyte locomotion, J Clin Invest 59:941, 1977. 22. Ignarro U: Stimulation of phagocytic release of neutral protease from human neutrophils by cholinergic amines and cyclic 3',S'-guanosine monophosphate, J Immunol 112:210 , 1974. 23. Pahwa SO, Smithwick EM, Grimes ER, O'Reilly RJ, Pahwa RN, and Good RA: Chemotactic defects in severe combined immunodeficiency, J PEDlATR 92:43, 1978.
Fatal overtreatment of accidental childhood intoxication Karl Ernst v. Muhlendahl," Ernst Gunter Krienke, and Reinhard Bunjes, Berlin, West Germany
IN 1976 we were consulted about a boy who had developed coma and seizures 16 hours after ingesting a small amount of a sedative. Upon closer questioning we discovered that the child, who had been fully conscious until this dramatic deterioration, had been severely overhydrated by a poorly controlled forced diuresis. The child subsequently died from cerebral edema . Since this incident we have directed more scrutiny to the problem of overtreatment. We have found additional instances in which the treatment, rather than the ingested substance, had been responsible for severe symptoms or From the Poison Control Center at the Children's Hospital, Freie Universitiu.
0022-3476/781121003+02$00.20/0
([j
1978 The C. V. Mosby Co .
death. The disturbing results of our critical examination of cases during the last 2lh years (and three still earlier ones from our files) are presented below.
RESULTS Data on 12 patients who developed coma and convulsions or died are given in the accompanying Table . Overtreatment was with virtual certainty the cause of these complications in nine (five of them fatal), and was probably the cause in the remaining 3 patients. Seven children had ingested amounts of drugs too small to produce severe symptoms, let alone be fatal; four of them died because of therapy. Three children (Patients 7, 9, and 11) had been in coma due to intoxication by
10.04
Brief clinical and laboratory observations
Table. Examples of childhood intoxication from the files of the Berlin Poison Control Center, in which coma and convulsions or death were induced by overtreatment Patient No.
Substance
Overtreatment
ingested"
with
I 2
DIfferent tablets (i) Homeopathic drug
3
Codeine (h)
4
Anionic surfactant (i) Crimidine (1) Atropa belladonna (i) Different tablets (h) Sedative (i) Sedative (h) Alcohol (?) Sedative (h) Carbamazepine (i)
Outcome
Forced diuresis Forced diuresis
Died Diedt
Laevallorphane (13 mg) NaC!
Diedt Survived
Nael Bemegrid
Diedt Survived
Forced diuresis
Survived
Forced diuresis Forced diuresis Glucose 40% Forced diuresis Forced diuresis
Died Survived Died Died Died
(i)
5 6 7
8 9 10 11 12
°In parentheses: amount ingested; i = insignificant, h = high. tWell-founded assumption, but no definite evidence that overtreatment was the cause.
hypnotics before being overhydrated. Patient II had temporarily regained consciousness before dying of cerebral edema. Patient 4, who had taken a small amount of an anionic surfactant, had been given by his mother 3 to 5 tablespoons of salt, diluted in water, but he vomited only once. Forty-five minutes later he was comatose and had general convulsions. Hypernatremia and hyperchloremia were treated by peritoneal dialysis. and he survived without neurologic sequelae. Patient 8 had become somnolent after ingestion of a moderate amont of methaqualone and promazine. Eight hours after the ingestion, forced diuresis was started. Nine hours thereafter he was coma tose, had general convulsions, and finally respiratory failure. Blood sodium concentration was decreased to 112 mEq/l, in this context an indication of severe overhydration.
The Journal oj Pediatrics December 197R
Patient 10, after ingestion of an undetermined amount of alcohol, was fully conscious when a glucose infusion was started. Inadvertent administration of 200 gm within 3V2 hours raised the blood glucose concentration to 1,470 mg/dl, and fatal brain damage occurred. Patient 11 had taken an unknown amount of carbarnazepine and became somnolent. Forced diuresis was started, and after seven hours the amount infused exceeded the production of urine by 1,700 ml. Carbamazepine levels in plasma taken before the child died were within the therapeutic range. DISCUSSION Among our consultations during the 30-month period under investigation, there were 36 childhood deaths allegedly due to intoxications. We think that the ratio of treatment-induced to poison-induced death may he higher than 5/31. Doctors may have hesitated to consult a poison control center in cases of overtreatment, or may have hidden the relevant facts in the imprecisions of their reports (if they had become aware at all of the existence of the problem). Gastric lavage, sodium chloride-induced emesis, and antidotal therapy are simple therapeutic means but are not entirely harmless. The most problematic and hence dangerous among the "simple" procedures, often applied automatically in the treatment of intoxications, is forced diuresis. Many pediatricians who believe that they are inducing forced diuresis are in fact practicing only forced infusion, without the necessary close supervision of electrolyte and water balance. Real emergencies due to accidental poisonings in children are rare. We have been consulted on approximately 30,000 children involved in suspected or real poisonings over these 2 112 years; only 36 of these were fatal. However, we feel that many less experienced doctors who have to cope with acute intoxications in children fail to weigh the indications for the different therapeutic measures with the necessary care. This is without doubt a common problem in Germany, and possibly in other countries too.
Volume 93 Number 6
5.
6.
7.
8.
9. 10.
I I.
12. 13.
14.
tion of function oflymphocytes, Clin Exp Immunol13: 171, 1973. Schellekens PThA, and Eijsvoogel VP: Lymphocyte transformation in vitro: IV. Recruitment in antigen-stimulated cullures, Clin Exp ImmunoI8:187, 1971. Hopkinson DA, Cook PS, and Harris H : Further data on the adenosine deaminase (ADA) polymorphism and a report of a new phenotype, Ann Hum Genet 32:361, 1969. Battistuzzi G, Scozzari R, Santolamazza P, Terrentano L, and Modiano G: Comparative activity of red cell adenosine dearninase allelic forms, Nature 251:7II, 1974. Weening RS, Roos D, and Loos JA: Oxygen consumption of phagocytizing cells in human leukocyte and granulocyte preparations. A comparative study, J Lab Clin Med 83:570, 1974. Solberg CO: Protection of phagocytized bacteria against antibiotics, Acta Med Scand 191:383, 1972. Astaldi A, Astaldi OCB, Wijermans P, Groenewoud M, Schellekens PTbA, and Eijsvoogel VP: Thymosin-induced human serum factor increasing cyclic AMP, J Immunol 119: 1106, 1977. Zigmond SH, and Hirsch JG : Leukocyte locomotion and chemotaxis. New methods for evaluation, and demonstration of a cell-derived chemotactic factor, J Exp Med 137:387, 1973. Worthington Enzyme Manual, Freehold, N.J., 1972, Worthington Biochemical Corp., p 100. Goldste in 1M, Roos D, Kaplan HB, and Weissmann G: Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis, J Clin Invest 56: 1155, 1975. Zuelzer WW, Mastrangelo R, Stulberg CS, Poulik HD, Page RH, and Thompson RI: Autoimmune hemolytic anemia. Natural history and Viral-immunologic interactions in childhood, Am J Med 48:80, 1970.
1003
15. Smith SD, Cho CT, Brahmacupta N, and Lenahan MF: Pulmonary involvement with cytomegalovirus infections in children, Arch Dis Child 52:441, 1977. 16. Sandman R, Ammann AJ, Grose C, and Wara DW: Cellular immunodeficiency associated with nucleoside phosphorylase deficiency. Immunologic and biochemical studies, Clin Imrnunol Immunopathol 8:247, 1977. 17. Borgers M, Verhaegen H, De Brabander M, Thoue F, van Reernpts J, and Genens G: Purine nucleoside phosphorylase, a possible histochemical marker for T-cells in man, J Immunol Methods 16:IOJ, 1977. 18. Groslong T, Horowitz S, Lovchik J, Davis A, and Hong R: Chronic cytomegalovirus infection and immunodeficiency: Antigen-driven malignancy? J PEDIATR 88:217, 1976. 19. Polmar SH, Stern RC, Schwartz AL, Wetzler EM, Chase PA, and Hirschhorn R : Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immune deficiency, N Engl J Med 295:1337, 1976. 20. Zegers BIM, Stoop JW , Hendrickx OFM, Wadman SK, and Staal GEl: Purine nucleoside phosphorylase deficiency associated with cellular immunodeficiency: immunologicaL follow-up during treatment, Proceedings of the Symposium of the Society for the Study of Inborn Errors in Man, New York, Academic Press, Inc (in press). 21. Wright DO, Kirkpatrick CH, and Gallin Jl: Effects of levarnisole on normal and abnormal leukocyte locomotion, J Clin Invest 59:941, 1977. 22. Ignarro U: Stimulation of phagocytic release of neutral protease from human neutrophils by cholinergic amines and cyclic 3',S'-guanosine monophosphate, J Immunol 112:210 , 1974. 23. Pahwa SO, Smithwick EM, Grimes ER, O'Reilly RJ, Pahwa RN, and Good RA: Chemotactic defects in severe combined immunodeficiency, J PEDlATR 92:43, 1978.
Fatal overtreatment of accidental childhood intoxication Karl Ernst v. Muhlendahl," Ernst Gunter Krienke, and Reinhard Bunjes, Berlin, West Germany
IN 1976 we were consulted about a boy who had developed coma and seizures 16 hours after ingesting a small amount of a sedative. Upon closer questioning we discovered that the child, who had been fully conscious until this dramatic deterioration, had been severely overhydrated by a poorly controlled forced diuresis. The child subsequently died from cerebral edema . Since this incident we have directed more scrutiny to the problem of overtreatment. We have found additional instances in which the treatment, rather than the ingested substance, had been responsible for severe symptoms or From the Poison Control Center at the Children's Hospital, Freie Universitiu.
0022-3476/781121003+02$00.20/0
([j
1978 The C. V. Mosby Co .
death. The disturbing results of our critical examination of cases during the last 2lh years (and three still earlier ones from our files) are presented below.
RESULTS Data on 12 patients who developed coma and convulsions or died are given in the accompanying Table . Overtreatment was with virtual certainty the cause of these complications in nine (five of them fatal), and was probably the cause in the remaining 3 patients. Seven children had ingested amounts of drugs too small to produce severe symptoms, let alone be fatal; four of them died because of therapy. Three children (Patients 7, 9, and 11) had been in coma due to intoxication by
10.04
Brief clinical and laboratory observations
Table. Examples of childhood intoxication from the files of the Berlin Poison Control Center, in which coma and convulsions or death were induced by overtreatment Patient No.
Substance
Overtreatment
ingested"
with
I 2
DIfferent tablets (i) Homeopathic drug
3
Codeine (h)
4
Anionic surfactant (i) Crimidine (1) Atropa belladonna (i) Different tablets (h) Sedative (i) Sedative (h) Alcohol (?) Sedative (h) Carbamazepine (i)
Outcome
Forced diuresis Forced diuresis
Died Diedt
Laevallorphane (13 mg) NaC!
Diedt Survived
Nael Bemegrid
Diedt Survived
Forced diuresis
Survived
Forced diuresis Forced diuresis Glucose 40% Forced diuresis Forced diuresis
Died Survived Died Died Died
(i)
5 6 7
8 9 10 11 12
°In parentheses: amount ingested; i = insignificant, h = high. tWell-founded assumption, but no definite evidence that overtreatment was the cause.
hypnotics before being overhydrated. Patient II had temporarily regained consciousness before dying of cerebral edema. Patient 4, who had taken a small amount of an anionic surfactant, had been given by his mother 3 to 5 tablespoons of salt, diluted in water, but he vomited only once. Forty-five minutes later he was comatose and had general convulsions. Hypernatremia and hyperchloremia were treated by peritoneal dialysis. and he survived without neurologic sequelae. Patient 8 had become somnolent after ingestion of a moderate amont of methaqualone and promazine. Eight hours after the ingestion, forced diuresis was started. Nine hours thereafter he was coma tose, had general convulsions, and finally respiratory failure. Blood sodium concentration was decreased to 112 mEq/l, in this context an indication of severe overhydration.
The Journal oj Pediatrics December 197R
Patient 10, after ingestion of an undetermined amount of alcohol, was fully conscious when a glucose infusion was started. Inadvertent administration of 200 gm within 3V2 hours raised the blood glucose concentration to 1,470 mg/dl, and fatal brain damage occurred. Patient 11 had taken an unknown amount of carbarnazepine and became somnolent. Forced diuresis was started, and after seven hours the amount infused exceeded the production of urine by 1,700 ml. Carbamazepine levels in plasma taken before the child died were within the therapeutic range. DISCUSSION Among our consultations during the 30-month period under investigation, there were 36 childhood deaths allegedly due to intoxications. We think that the ratio of treatment-induced to poison-induced death may he higher than 5/31. Doctors may have hesitated to consult a poison control center in cases of overtreatment, or may have hidden the relevant facts in the imprecisions of their reports (if they had become aware at all of the existence of the problem). Gastric lavage, sodium chloride-induced emesis, and antidotal therapy are simple therapeutic means but are not entirely harmless. The most problematic and hence dangerous among the "simple" procedures, often applied automatically in the treatment of intoxications, is forced diuresis. Many pediatricians who believe that they are inducing forced diuresis are in fact practicing only forced infusion, without the necessary close supervision of electrolyte and water balance. Real emergencies due to accidental poisonings in children are rare. We have been consulted on approximately 30,000 children involved in suspected or real poisonings over these 2 112 years; only 36 of these were fatal. However, we feel that many less experienced doctors who have to cope with acute intoxications in children fail to weigh the indications for the different therapeutic measures with the necessary care. This is without doubt a common problem in Germany, and possibly in other countries too.
