大量砒霜攝取導致之急性腎衰竭及死亡大量砒霜攝取導致之急性腎衰竭及死亡Acute Renal Failure and Mortality Acute Renal Failure and Mortality Following Massive Arsenic Trioxide Following Massive Arsenic Trioxide IngestionIngestion

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 InformationPatient Information

Age: 57-year-oldGender: maleOccupation: Teacher (chemistry)Marital status: married

ChiefChief ComplaintComplaintIngestion of 30 grams of asrsenics

trioxides ( 砒霜 ).

Present IllnessPresent 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 ExaminationPhysical ExaminationT: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.

Laboratory (16:13)Laboratory (16:13)

WBC(/uL) 11800 BUN(mg/dL) N/A

Hb(g/dL) 15.3 Cr(mg/dL) 1.4

MCV(fL) 87.5 Na(meq/L) 137

RDW(%) 13.5 T. Bil(mg/dL) 1.0

Platelet(uL) 179000 K(meq/L) 3.7

Seg(%) 91.4 ALT(U/L) 103

PT INR N/AUric

acid(mg/dL)5.7

aPTT N/A Sugar( mg/dL) 144

Sinus Tachycardia

15:30-Arrived at CGMH ERDecontamination, Gastric lavage, IVF supportCheck Arsenic level

17:00-Contacted with 台北榮總解毒劑中心 for antidote.

21:00-Respiratory distress, hypoxic respiratory failure and shock occurred.

Fluid resuscitation(1000ml) and high dose norepinephrine were prescribed for shock.

Arterial blood gasArterial blood gas beforebefore intubationintubation(21:00)(21:00)

pH: 7.331PaO2 82.9mmHg (FiO2: 100%)PCO2: 23.5mmHgHCO3: 12.1mmol/LSBE:-13.8mmol/L

ManagementManagement

22:20-endotracheal intubation with mechanical ventilator support.Transfer to ICU.Continue fluid resuscitation with high dose inotropic agents for shock status1st 2,3- dimercaptol propanesulfonic acid (DMPS) 250mg IVF at 23:30(9hrs).

Laboratory data at ICULaboratory data at ICU

WBC(/uL) 49600

Hb(g/dL) 15.4 Cr(mg/dL) 3.68

Platelet 166000 Na(meq/L) 145

Band(%) 12.1 Ca(mg/dL) 7.4

Lympho(%) 10.0 K(mEq/L) 2.8

Seg(%) 73 ALT(U/L) 98

PT INR N/ATroponin I(ng/mL)

20.958

aPTT N/ALactate(mg/

dL)99.05

12/31 2:0012/31 2:00 (12(12 hrshrs afterafter ingestion)ingestion)

Arrange CVVHD for metabolic acidosis and shock.

Asystole before CVVHD was set. CPCR but failure.

Critical AAD.

Arsenic serum levelArsenic serum level (1.5(1.5 hrhr afterafter exposure)exposure)

730ug/L (normal range: <20ug/L)

DiscussionDiscussion 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

Inorganic arsenics is toxic. Postgrad Med J 2003

79: 391-396

ArsenicsArsenics As2O3: most common form in

environment, especially in water, soil or seafood, color pigments.

Murder weapons with sugar used by ancient Chinese.

Treatment of acute myelogenous leukemia -M3: (relapse status after ATRA).

Cosmetic products, <5ppm.

Postgrad Med J 2003 79 391-396

PharmacokineticsPharmacokinetics

Absorbed rapidly from GI tract with 100% bioavailability.

Rapid redistribution from blood (half life 1 hr.)

Inorganic arsenic can be either methylated to form monomethylarsonic acid or dimethylated as in dimethylarsinic acid.

K.Jonova: Journal of 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: Journal of Applied.

Toxicology. 2011; 31: 95–107

PEDIATRICS Vol. 116 No. 1 July 2005

Pyruvate+thiamine pyrophosphate(TPP)-> hydroethylTPP+lipoamide->aceyl-CoA+dihydrolipoamide

PEDIATRICS Vol. 116 No. 1 July 2005

Acute poisoningAcute poisoning ofof ArsenicsArsenics

Lethal dose: 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 Acute tubular necrosis or

hemogloburinuria due to hemolysis may occur.

PEDIATRICS Vol. 116 No. 1 July 2005

ManagementManagement Decontamination:

Skin decontaminationGI decontamination: gastric lavage and active charcoal.

Fluid resuscitation to maintain urine flow.

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

2,3,2,3, d dimercaptolimercaptol propanesulfonicpropanesulfonic acid acid (DMPS)(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 EliminationExtracorporeal 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