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大量砒霜攝取導致之急性腎衰竭及死亡 Acute Renal Failure and Mortality Following Massive Arsenic Trioxide Ingestion. 侯羿州 , 林杰樑 , 顏宗海 Yi-Chou Hou, Ja-Liang Lin, Tzung-Hai Yen 林口長庚紀念醫院 腎臟系 臨床毒物科 Chang Gung Memorial Hospital, Linkou department, Taoyun, Taiwan. Patient Information. Age: 57-year-old Gender: male
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大量砒霜攝取導致之急性腎衰竭及死亡Acute Renal Failure and Mortality Following Massive Arsenic Trioxide Ingestion • 侯羿州, 林杰樑, 顏宗海Yi-Chou Hou, Ja-Liang Lin, Tzung-Hai Yen • 林口長庚紀念醫院腎臟系臨床毒物科Chang Gung Memorial Hospital, Linkou department, Taoyun, Taiwan
Patient Information • Age:57-year-old • Gender: male • Occupation: Teacher(chemistry) • Marital status: married
ChiefComplaint • Ingestionof30gramsof asrsenicstrioxides (砒霜).
Present Illness • 14:00 on 12/30-his colleagues found him taking 30 grams of arsenic trioxide(砒霜). • Excessive salivation and epigastralgia with persistent vomiting. • Shortness of breath and abdominal pain occurred concurrently. • 15:30-he was referred to our ER.
Physical Examination • T:37℃ P:80 beats/min R:16times /min BP:116/81mmHg • Consciousness: Clear, E 4 V 5 M 6 • HEENT: Sclera: not icteric; Conjunctiva: not pale Oral cavity : intact oral mucosa • Chest: Symmetric expansion. Bilateral clear breathing sounds. • Heart: regular heart beat without murmur. • Abdomen: Soft and flat. No tenderness. No hepatosplenomegaly. • Extremities: No pitting pitting edema.
15:30-ArrivedatCGMHERDecontamination, Gastriclavage,IVFsupportCheckArseniclevel • 17:00-Contacted with 台北榮總解毒劑中心 forantidote. • 21:00-Respiratorydistress,hypoxic respiratory failure and shock occurred. • Fluid resuscitation(1000ml) and high dose norepinephrine were prescribed for shock.
Arterial blood gasbeforeintubation(21:00) • pH: 7.331 • PaO2 82.9mmHg (FiO2: 100%) • PCO2: 23.5mmHg • HCO3: 12.1mmol/L • SBE:-13.8mmol/L
Management • 22:20-endotrachealintubation withmechanicalventilatorsupport. • Transfer to ICU. • Continuefluidresuscitationwithhighdoseinotropicagentsforshockstatus • 1st 2,3- dimercaptolpropanesulfonicacid (DMPS) 250mgIVFat 23:30(9hrs).
12/31 2:00(12hrsafteringestion) • ArrangeCVVHD for metabolic acidosis and shock. • AsystolebeforeCVVHDwasset.CPCRbutfailure. • Critical AAD.
Arsenic serum level(1.5hrafterexposure) • 730ug/L(normalrange:<20ug/L)
Discussion • Arsenics is one of the most toxic metals derived from the natural environment. • Most common form: 5+, 3+, 3- • Organic : with hydrogen and oxygenInorganic: with Sulfur, chloride or oxygen • Inorganicarsenicsistoxic. • Postgrad Med J 2003 79: 391-396
Arsenics • As2O3: most common form in environment, especially in water, soil or seafood, color pigments. • Murder weapons with sugar used by ancient Chinese. • Treatmentofacute myelogenous leukemia-M3: (relapse status after ATRA). • Cosmetic products, <5ppm. Postgrad Med J 2003 79391-396
Pharmacokinetics • Absorbed rapidly from GI tract with 100% bioavailability. • Rapid redistribution from blood(half life 1 hr.) • Inorganic arsenic can be either methylated to form monomethylarsonicacid or dimethylated as in dimethylarsinicacid. K.Jonova:Journalof Applied. Toxicology. 2011; 31: 95–107
The methylation of inorganic arsenic has been considered to be a detoxification mechanism • Clearance from bloodPhase 1: from serum to tissue(90%, 30 mins)Phase 2: to tissue(RBC, 10%)Phase 3: from tissues and RBC into plasma then renal elimination. K.Jonova:Journalof Applied. Toxicology. 2011; 31: 95–107
Pyruvate+thiamine pyrophosphate(TPP)-> hydroethylTPP+lipoamide->aceyl-CoA+dihydrolipoamide PEDIATRICS Vol. 116 No. 1 July 2005
Acute poisoningofArsenics • Lethaldose:100-500mg • <24hrs:Hematemesis and diarrhea within 1 to 4 hs after ingestion. • Garlic odor. • Gastrointestinal volume loss due to capillary permeability change. • QTc prolongation, arrhythmia, cerebral edema, microhemorrhage • Acutetubularnecrosisor hemogloburinuria due to hemolysis mayoccur. PEDIATRICS Vol. 116 No. 1 July 2005
Management • Decontamination:SkindecontaminationGIdecontamination: gastric lavage and active charcoal. • Fluid resuscitation tomaintainurineflow. • Chelating agents:DMPS, BAL MUNDY SW: GOLDFRANK’S TOXICOLOCIAL EMERGENCIES, 2010
Dimercaprol( BAL in oil) • Every 50 mg BAL binds to 30 mg arsenics. • Administrate as intramuscular injection. • Bioavailability is unpredictable in patients with shock. • The only chelating agent to cross blood-brain barrier. Journal of Anal Toxicol. 1989; 13:310 –312
2,3,dimercaptolpropanesulfonicacid (DMPS) • Water analog to BAL. • Chelating to metabolite of arsenics, especially first methylated arsenics. • Increase urine excretion (>3 folds) within 2 hours if given as early as possible. J Pharmacol Exp Ther. 1997;282:192–200
Extracorporeal Elimination • HD ineffective: low dialysate arsenic concentration in several studies suggested rapid distribution to tissue. • DMPS-As is not dialyzable. • HD when uremia symptoms develop. • CVVHDF may be considered for convective mass transport.(?) PEDIATRICS Vol. 116 No. 1 July 2005