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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.

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Paraquat poisoning

Dr. Wong Oi Fung

TMH


History case 1
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
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
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 21
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


Progress1
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
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

H3C +N N+ CH3 2Cl-


Paraquat as herbicide
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


Type 1 and type 2 pulmonary epithelial cells

O2

NADPH

Oxidising cytochrome P-450 reductase

PQ+

Reduced cytochrome P-450 reductase

NADP

PQ2+

O2

PQ in blood

Redox cycling of paraquat

O2 + O2 + 2H+ H2O2 + O2

GSH GSSG

H2O

O2

Fe3+

OH + OH-

Lipid peroxidation

O2

Fe2+

H2O2


Clinical features
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
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
Investigation

  • Blood test

    • RFT, LFT, ABG

  • CXR and ECG

  • ?? Paraquat level

Paraquat nomogram

5

4

Plasma paraquat ug/ml

3

10%

2

50%

90%

1

0

4 8 12 16 20 24 28

Hours post ingestion


Investigation1
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


Type 1 and type 2 pulmonary epithelial cells

O2

NADPH

Oxidised cytochrome P-450 reductase

PQ+

??hypoxic atomospheres

HP/Fuller’s Earth

Reduced cytochrome P-450 reductase

NADP

PQ2+

O2

PQ in blood

NAC

O2 + O2 + 2H+ H2O2 + O2

DFO

GSH GSSG

H2O

O2

Fe3+

OH + OH

Lipid peroxidation

Methylprednisolone &cyclophosphamide

O2

Fe2+

H2O2


Gut decontamination
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
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
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
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;53:620-621



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