Paraquat poisoning Dr. Wong Oi Fung TMH

History (case 1) 76/M Hx of knee pain otherwise good past health Attended A&E on 5/12/2004 Quarreled with his neighbor; sprayed paraquat over his eyes Vital signs: Bp117/79; Pulse 85/min; SpO2 99% RA; GCS 15/15 Cat. 3

Progress NS irrigation to both eyes RFT and ABG normal Close monitoring in medical ward Observed for 1 week; RFT all along normal; no respiratory distress Seen by eye doctor Discharged after 1 week of observation Referred to eye clinic for follow-up

History (case 2 ) 70/M History of HT and gout Attended on 13/2/2005 for paraquat ingestion Committed suicide because of chronic joint pain Drank ~ 100 ml paraquat ( 24% paraquat dichloride)

History (case 2) Vital signs: BP 159/70; pulse 77bpm; afebrile; SpO2 100% on RA; GCS 15/15 Cat. 2 CXR  clear lung field ECG  SR Poor prognosis explained to relatives Admitted to medical ward

Progress Hemoperfusion tried but developed high fever and confusion with tachycardia and stopped Rapidly deteriorated with confusion, oral ulceration and dyspnoea ↓Renal function: Cr 122  337 Succumbed on 15/2/2005

Discussion Paraquat –1,1’ –dimethyl-4,4’-dipyridylium –Bipyridyl herbicides Exposure: –Toxic ingestion  intentional –Dermal exposure  occupational –Other e.g. eye Fetal dose 20 to 40mg/kg H 3 C + N N + CH 3 2Cl -

Paraquat as herbicide As contact herbicide with low environmental toxicity due to rapid deactivation upon soil contact In plants – disrupts photosynthesis by inhibiting the electron transport chain In humans –Poorly absorbed (1-5% of oral dose absorbed in gut ) –Vol. of distribution 2 to 8 Liters/kg –Cause multiple organ damage

PQ in blood Type 1 and type 2 pulmonary epithelial cells NADPH NADP Oxidising cytochrome P- 450 reductase Reduced cytochrome P- 450 reductase PQ + PQ 2+ O2O2 O2O2 O 2 + O 2 + 2H + H 2 O 2 + O 2 O2O2 O2O2 Fe 3+ Fe 2+ OH + OH - H2O2H2O2 Redox cycling of paraquat Lipid peroxidation H2OH2O GSH GSSG

Clinical features Resp. system –Delayed (3 to 14 days) progressive pulmonary fibrosis Renal system –Acute renal failure (within 24 to 96 hours) GI system –N, V & D –Burning in oral mucosa and hemorrhagic ulceration CVS –Cerebral edema and brain damage CNS –Ventricular arrhythmias, hypotension and cardiorespiratory arrest Eye –Protracted opacification of the cornea Skin –Dermatitis –Well adsorbed in injured skin  severe system toxicity Other –Methemoglobinemia, transient reversible liver injury

Management Airway management and adequate ventilation High O2  CONTRAINDICATED Use the lowest O2 levels possible to limit pulmonary complication Decontamination (Fuller’s earth/ activated charcoal) IVF to maintain adequate urine output Hemodialysis or hemoperfusion Administration of “antidotes” –Antioxidants NAC or deferoxamine –Immunosuppressive therapy Explain the poor prognosis to patient’s relative

Investigation Blood test –RFT, LFT, ABG CXR and ECG ?? Paraquat level % 50% 10% Hours post ingestion Plasma paraquat ug/ml Paraquat nomogram

Investigation Urine dithionite test –Paraquat stable blue radical ion –Colourless or light blue  mild poisoning –Navy or dark blue  moderate to sever poisoning –??validity Urine paraquat concentration depend on renal function Urine production as poisoning progress since paraquat caused renal failure Sodium thionite under alkaline condition

PQ in blood Type 1 and type 2 pulmonary epithelial cells NADPH NADP Oxidised cytochrome P- 450 reductase Reduced cytochrome P- 450 reductase PQ + PQ 2+ O2O2 O2O2 O 2 + O 2 + 2H + H 2 O 2 + O 2 O2O2 O2O2 Fe 3+ Fe 2+ OH + OH H2O2H2O2 Lipid peroxidation H2OH2O GSH GSSG HP/Fuller’s Earth DFO Methylprednisolone &cyclophosphamide NAC ??hypoxic atomospheres

Gut Decontamination Fuller’s Earth Vs Activated charcoal –Animal study showed: No significant difference found in the effectiveness of either adsorbent Administration of an adsorbent as early as possible will reduce paraquat absorption from the GI tract Activated charcoal is still effective in lowering serum paraquat concentration when given >1hour after ingestion of paraquat –Idid SZ. Lee CY.: Effect of Fuller’s Earth and activated charocal on oral absorption of paraquat in rabbits.Clinical & Experimental pharmacology & Physiology. 23(8):679-81, 1996 Aug

Extracorporeal Elimination Techniques Hemodialysis/hemoperfusion Do they increased the survival rate?? –Probably not. –When these techniques are initiated, potential lethal concentration of paraquat have already been attained in the highly vascular tissue of vital organs and in the pneumocytes –Bismuth C. Scherrmann Jm. Garnier R. Baud FJ. Pontal PG.: Elimination of paraquat. Human Toxicology. 6(1):63-7, 1987 Jan. Hemodialysis –Paraquat NOT dialyze effectively –Supportive treatment for renal failure

Immunosuppressive therapy RCT of pulse methylprednisolone & cyclophosphamide in paraquat poisoning showed survival: 43% to 72/% (p=0.008) –Lin in 1999 Really benefit?? –Exclude “fulminant” poisoning (died within 7 days); 50% was excluded –Reanalysis on an intention-to-treat basis showed an improvement NOT significant at the 0.05 statistical level :18% to 32% (p=0.095 )

Treatment Deferoxamine and NAC – rat mortality and morbidity Lung transplantation –Successful outcome after single lung transplantation in paraquat poisoning has been reported –Licker, Marc: Single lung transplantation for adult respiratory distress syndrome after paraquat poisoning. Thorax 1998;53:

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