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Changes in pediatric toxic dose of acetaminophen
CORRESPONDENCE
323
9. Graham D, McGahren ED, Tribbble CG, et al: Use of videoassisted thoracic surgery in the treatment of chylothorax. Ann Thoracic Surg 1994;57:1507-1512
CHANGES IN PEDIATRIC TOXIC DOSE OF ACETAMINOPHEN To the Editor:—After reading the interesting case of Waseem et al,1 we would like to make some comments. As the authors say, classically the toxic dose of acetaminophen in pediatric acute overdose is 150mg/Kg.2 However, in children under 6 years with acute acetaminophen overdose (AAO) is very rare the development of hepatotoxicity,3,4 and fatal cases are scarce.5 This is fundamentally due to higher capacity of drug metabolism by sulfurconjugation metabolic via, with a reduction of oxidative via use, which generates hepatotoxic metabolite (Nacetil-benzoquinone-imine),6 and probably to better efficiency for drug elimination respect to adults.7 In this way, recent studies, which included 2,000 children under 6 years with AAO, adviced the increase of the toxic dose ingested at figures between 200-250 mg/Kg,4,8,9 when treating acute ingestions of previously healthy children, without hepatic illnesses, underfed or infectious processes.10 Of these figures chronic ingestions up to 75 mg/Kg/d must also be excluded,11 as in the reported case, or when factors or other toxics which delayed gastric transit are present. However there is disagreement about how therapeutics measures should be performed under these figures. Although Mohler et al suggest that no therapeutic measures should be made under 200 mg/Kg,4 Caravati et al suggest the provocation of vomiting at home during the first 60 minutes postingestion,8 and Anderson et al only administer activated charcoal in the first hour, under 250 mg/kg.9 On the other hand Anderson et al recommend performed plasma acetaminophen determination in those patients under suspicion of toxic ingestion at 2 hours after exposition, instead of the classic 4 hours. They base themselves on the development of a toxicokinetic model for pediatric formulations (liquid) that show a quicker absortion and therefore earlier plasma peak levels. In this case, the possible toxic dose at 2 hours would be 225 mg/L instead of 150 mg/L at 4 hours.9 We should remember that the Mathew-Rumack Normogram12 was calculated using healthy adults volunteers, with solid presentations, and at a time when more used presentation in children was a mixture on acetaminophen and propoxifene, with delay in gastric emptying.13 In children less than 6 years, with current existing data, it seems reasonable and safer to increase the toxic level of acetaminophen in acute overdose to 200 mg/Kg, with the exceptions before exposed. This attitude would take a lower number of transfers to the ED, diagnostic and therapeutics measures, and would contribute to a decrease in parents and children anxiety. GUILLERMO BURILLO-PUTZE, MD Emergency Department Hospital Universitario de Canarias Tenerife, Spain SANTIAGO MINTEGUI, MD Pediatric Emergency Department Hospital de Cruces Bilbao, Spain PERE MUNNE, MD Clinical Toxicology Unit Emergency Department Hospital Clinic Barcelona, Spain
© 2004 Elsevier Inc. All rights reserved. 0735-6757/04/2204-0023$30.00/0 doi:10.1016/j.ajem.2004.04.018
References 1. Waseen M, Bomann S, Gernsheimer J, et al: Unusual presentation of acetaminophen toxicity. Am J Emerg Med 2003;21:88-89 2. Osterhoudt K, Shannon M, Henretig F: Toxicologic Emergencies, in Fleisher GR, Ludwig S (eds): Textbook of Pediatric Emergency Medicine. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 899-901 3. Penna A, Buchanan N: Paracetamol poisoning in children and hepatotoxicity. Br J Clin Pharmacol 1991;32:143-9 4. Mohler CR, Nordt SP, Williams SR, et al: Prospective evaluation of mild to moderate pediatric acetaminophen exposures. Ann Emerg Med 2000;35:239-44 5. Alander SW, Dowd M, Bratton S, et al: Pediatric acetaminophen overdose. Risk factors associated wuth hepatocellular injury. Arch Pediatr Adolesc Med 2000;154:346-50 6. Sztajnkrycer MJ, Bond GR: Chronic acetaminophen overdosing in children: risk assessment and management. Curr Opin Ped 2001;13:177-182 7. Maxwell GM: Principles of pediatric pharmacology. New York, Oxford University press, 1984, p 96 8. Anderson BJ, Holford NH, Armishaw JC, et al: Predicting concentrations in children presenting with acetaminophen overdose. J Pediatr 1999;135:290-295 9. Caravati EM: Unintentional acetaminophen ingestion in children and the potential for hepatotoxicity. J Toxicol Clin Toxicol 2000;38:291-296 10. Peire MA, Lucena MJ, Ruiz-Extremera A, et al: Toxicidad hepa´ tica por fa´ rmacos. Do´ nde estamos y hacia do´ nde caminamos. An Esp Pediatr 2002;56:434-442 11. Bizovi KE, Smilkenstein MJ: Acetaminophen, in Goldfrank’s Toxicologic Emergencies, 7 ed. New York, Mc Graw-Hill, 2002, pp 489-490 12. Rumack BH, Mathew H: Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871 13. Rumack BH: Acetaminophen overdose? A quick answer. J Pediatr 1999;135:269-270
SPONTANEOUS REDUCTION OF A SMALL BOWEL INTUSSUSCEPTION IN A PATIENT WITH HENOCH SCHONLEIN PURPURA To the Editor:—A 3-year-old girl with a 2-week history of afebrile upper respiratory infection (URI) symptoms and a 4-day history of a diffuse purplish rash presented to the emergency department (ED) with intermittent crampy abdominal pain, bilious emesis, and decreased urine output. On arrival to the ED, her vitals were pulse (P) 180 beats/min, blood pressure (BP) 103/53 mmHg, respiration rate (RR) of 40 breaths/min. She had dry mucous membranes, diffuse abdominal tenderness, guaiac-positive stool, and multiple palpable purpura to her face, trunk, arms, lower extremities and buttocks. Laboratory studies revealed a hemoglobin (HgB) count of 13.2 with 252,000 platelets; urinalysis revealed ketones but no red blood cells (rbcs) nor protein. During her ED course, she was given aggressive fluid resuscitation. An abdominal ultrasound was obtained demonstrating a small bowel intussusception in the right subhepatic region (Figs 1, 2). On completion of fluid resuscitation, the patient exhibited improvement in heart rate with less vomiting and decreased abdominal pain. After consultation with the surgical service, a repeat ultrasound was obtained revealing resolution of the intussusception and a bowel loop with thickened walls. The patient was placed on oral steroids and admitted for overnight observation and monitoring. She was discharged home the next day with complete resolution of abdominal pain.
© 2004 Elsevier Inc. All rights reserved. 0735-6757/04/2204-0024$30.00/0 doi:10.1016/j.ajem.2004.04.019
323
9. Graham D, McGahren ED, Tribbble CG, et al: Use of videoassisted thoracic surgery in the treatment of chylothorax. Ann Thoracic Surg 1994;57:1507-1512
CHANGES IN PEDIATRIC TOXIC DOSE OF ACETAMINOPHEN To the Editor:—After reading the interesting case of Waseem et al,1 we would like to make some comments. As the authors say, classically the toxic dose of acetaminophen in pediatric acute overdose is 150mg/Kg.2 However, in children under 6 years with acute acetaminophen overdose (AAO) is very rare the development of hepatotoxicity,3,4 and fatal cases are scarce.5 This is fundamentally due to higher capacity of drug metabolism by sulfurconjugation metabolic via, with a reduction of oxidative via use, which generates hepatotoxic metabolite (Nacetil-benzoquinone-imine),6 and probably to better efficiency for drug elimination respect to adults.7 In this way, recent studies, which included 2,000 children under 6 years with AAO, adviced the increase of the toxic dose ingested at figures between 200-250 mg/Kg,4,8,9 when treating acute ingestions of previously healthy children, without hepatic illnesses, underfed or infectious processes.10 Of these figures chronic ingestions up to 75 mg/Kg/d must also be excluded,11 as in the reported case, or when factors or other toxics which delayed gastric transit are present. However there is disagreement about how therapeutics measures should be performed under these figures. Although Mohler et al suggest that no therapeutic measures should be made under 200 mg/Kg,4 Caravati et al suggest the provocation of vomiting at home during the first 60 minutes postingestion,8 and Anderson et al only administer activated charcoal in the first hour, under 250 mg/kg.9 On the other hand Anderson et al recommend performed plasma acetaminophen determination in those patients under suspicion of toxic ingestion at 2 hours after exposition, instead of the classic 4 hours. They base themselves on the development of a toxicokinetic model for pediatric formulations (liquid) that show a quicker absortion and therefore earlier plasma peak levels. In this case, the possible toxic dose at 2 hours would be 225 mg/L instead of 150 mg/L at 4 hours.9 We should remember that the Mathew-Rumack Normogram12 was calculated using healthy adults volunteers, with solid presentations, and at a time when more used presentation in children was a mixture on acetaminophen and propoxifene, with delay in gastric emptying.13 In children less than 6 years, with current existing data, it seems reasonable and safer to increase the toxic level of acetaminophen in acute overdose to 200 mg/Kg, with the exceptions before exposed. This attitude would take a lower number of transfers to the ED, diagnostic and therapeutics measures, and would contribute to a decrease in parents and children anxiety. GUILLERMO BURILLO-PUTZE, MD Emergency Department Hospital Universitario de Canarias Tenerife, Spain SANTIAGO MINTEGUI, MD Pediatric Emergency Department Hospital de Cruces Bilbao, Spain PERE MUNNE, MD Clinical Toxicology Unit Emergency Department Hospital Clinic Barcelona, Spain
© 2004 Elsevier Inc. All rights reserved. 0735-6757/04/2204-0023$30.00/0 doi:10.1016/j.ajem.2004.04.018
References 1. Waseen M, Bomann S, Gernsheimer J, et al: Unusual presentation of acetaminophen toxicity. Am J Emerg Med 2003;21:88-89 2. Osterhoudt K, Shannon M, Henretig F: Toxicologic Emergencies, in Fleisher GR, Ludwig S (eds): Textbook of Pediatric Emergency Medicine. Philadelphia, Lippincott Williams & Wilkins, 2000, pp 899-901 3. Penna A, Buchanan N: Paracetamol poisoning in children and hepatotoxicity. Br J Clin Pharmacol 1991;32:143-9 4. Mohler CR, Nordt SP, Williams SR, et al: Prospective evaluation of mild to moderate pediatric acetaminophen exposures. Ann Emerg Med 2000;35:239-44 5. Alander SW, Dowd M, Bratton S, et al: Pediatric acetaminophen overdose. Risk factors associated wuth hepatocellular injury. Arch Pediatr Adolesc Med 2000;154:346-50 6. Sztajnkrycer MJ, Bond GR: Chronic acetaminophen overdosing in children: risk assessment and management. Curr Opin Ped 2001;13:177-182 7. Maxwell GM: Principles of pediatric pharmacology. New York, Oxford University press, 1984, p 96 8. Anderson BJ, Holford NH, Armishaw JC, et al: Predicting concentrations in children presenting with acetaminophen overdose. J Pediatr 1999;135:290-295 9. Caravati EM: Unintentional acetaminophen ingestion in children and the potential for hepatotoxicity. J Toxicol Clin Toxicol 2000;38:291-296 10. Peire MA, Lucena MJ, Ruiz-Extremera A, et al: Toxicidad hepa´ tica por fa´ rmacos. Do´ nde estamos y hacia do´ nde caminamos. An Esp Pediatr 2002;56:434-442 11. Bizovi KE, Smilkenstein MJ: Acetaminophen, in Goldfrank’s Toxicologic Emergencies, 7 ed. New York, Mc Graw-Hill, 2002, pp 489-490 12. Rumack BH, Mathew H: Acetaminophen poisoning and toxicity. Pediatrics 1975;55:871 13. Rumack BH: Acetaminophen overdose? A quick answer. J Pediatr 1999;135:269-270
SPONTANEOUS REDUCTION OF A SMALL BOWEL INTUSSUSCEPTION IN A PATIENT WITH HENOCH SCHONLEIN PURPURA To the Editor:—A 3-year-old girl with a 2-week history of afebrile upper respiratory infection (URI) symptoms and a 4-day history of a diffuse purplish rash presented to the emergency department (ED) with intermittent crampy abdominal pain, bilious emesis, and decreased urine output. On arrival to the ED, her vitals were pulse (P) 180 beats/min, blood pressure (BP) 103/53 mmHg, respiration rate (RR) of 40 breaths/min. She had dry mucous membranes, diffuse abdominal tenderness, guaiac-positive stool, and multiple palpable purpura to her face, trunk, arms, lower extremities and buttocks. Laboratory studies revealed a hemoglobin (HgB) count of 13.2 with 252,000 platelets; urinalysis revealed ketones but no red blood cells (rbcs) nor protein. During her ED course, she was given aggressive fluid resuscitation. An abdominal ultrasound was obtained demonstrating a small bowel intussusception in the right subhepatic region (Figs 1, 2). On completion of fluid resuscitation, the patient exhibited improvement in heart rate with less vomiting and decreased abdominal pain. After consultation with the surgical service, a repeat ultrasound was obtained revealing resolution of the intussusception and a bowel loop with thickened walls. The patient was placed on oral steroids and admitted for overnight observation and monitoring. She was discharged home the next day with complete resolution of abdominal pain.
© 2004 Elsevier Inc. All rights reserved. 0735-6757/04/2204-0024$30.00/0 doi:10.1016/j.ajem.2004.04.019