Paraquat Poisoning - PowerPoint Presentation

Slide1

Paraquat PoisoningLessons from a Large Cohort

Indika Gawarammana

(MD, FRCPE, PhD)

Department of Medicine and South Asian Clinical Toxicology Research Collaboration

Faculty of Medicine- University of Peradeniya

Sri LankaSlide2

Paraquat- historyFirst described in 1882Electron donation to PQ forms a stable PQ.+

Used as an oxidation-reduction indicator

Introduced as a herbicide in 1962Slide3

Paraquat

in agriculture

Non-systemic, fast acting

Rain-fast, quickly deactivated in soil

No tillage preserves soil structure

No damage to surrounding crops

Broad spectrum, no weed resistance

Key crops in Sri Lanka are tea and riceSlide4

Paraquatproportion of deathSoSlide5

Generates free radicalsActivation of NFkB

NFkB

is

translocated

into the

nucleus,

binds

to promoter

regions

induces target genes involved in inflammationSlide6

Diagnosis

DITHIONITE

REDUCTION OF PARAQUAT

Sodium

dithionite

alkali

PARAQUAT

PARAQUAT RADICAL ION (BLUE)

Paraquat is converted to a blue colour by sodium dithionite

Limit

of

detection of

plasma and

urine:

2-3 µg/mL

Slide7

Plasma paraquat concentrationSlide8

symptomsNausea and vomiting in 81.6%Burning oral pain in 62.5%Odynophagia 30%

Abdominal pain in 57.5%

Low GCS is uncommon (8%)- but all recover within hoursSlide9

“Paraquat Tongue”Slide10

Peripheral burning sensation

73%- median time to death

36 hrs

25%- median time to death

50hrsSlide11

Proportion of deaths- volume of ingestion

Log

Rank (Chi square 79.69, p<0.0001)Slide12

Case fatality 73.9% (95% CI 69-78). Median time to death1.53

days (IQR 0.5-3.7).Slide13

Clinical courseSevere toxicity = rapid death from MOFOthers= slow death over days due to hypoxiaSlide14

Respiratory rate

survivorsSlide15

Biochemical evolutionAdmission creatinine

2.05 mg/

dL

(IQR 1.3-3.1)

0.9mg/

dL

(IQR 0.7-1.3)Slide16

EvolutionSlide17

Admission WBCSlide18

OR 81, 95% CI 67-84Slide19

EvolutionSlide20

Admission ALTSlide21

EvolutionSlide22

TreatmentSupportive careN acetylcysteine, DFO, Vitamin E

ImmunosuppressionSlide23

haemodialysis and haemoperfusion

lung

plasma

tissueSlide24

Immunosuppressionpopular Inconclusive evidence

(Eddleston M et al QJM.

2003 and

Agarwal et al Singapore Med J.

2007)

South Asian Clinical Toxicology Research Collaboration Faculty of Medicine, University of PeradeniyaSlide25

RCT in Sri Lanka

Chi

squared 0.74,

p=0.34Slide26

ROC curves

Area under the curve

1= perfect testSlide27

Assessment of prognosisAdmission plasma paraquat concentration

Plasma paraquat

SIPP scoreSlide28

Number

Number and % deaths

Positive test

418

251 (60%)

Negative test

149

7 (4.7%)

Semi-quantitative

Urine dithionite testSlide29

Negative test= survivalSensitivity of 0.97 (95% CI 0.94-.98) Specificity of 0.45 (95% CI 0.4-0.5) Negative predictive value of 0.95 (95% CI 0.90-0.98)

Easy to perform, cheap

Negative tests= survival

Positive tests: need further evaluationSlide30

Admission creatinine>1.26mg/dL

Sensitivity

of 78% (95% CI: 69-85),

specificity of 73% (95% CI: 59-84) [positive likelihood ratio 2.91]Slide31

Creatinine >2.64mg/dL

(OR 16.7, 95% CI: 3.8-72, specificity: 0.96 (95% CI 0.87-0.99),

PPV 0.95 (95% CI 0.85-0.99, p<0.001). Slide32

Median rise of serum creatinine within 24 hours

Survivors (0.2mg/

dL

, IQR 0-0.6)

Deceased (2mg/

dL

, IQR 1-3) ( p<0.0001

).

Cut off rise of 0.88mg/dL (95% CI 0.82-0.94, p<0.0001) Slide33

Rise of creatinineCut off rise of 0.88mg/dL (95% CI 0.82-0.94, p<0.0001)

Sensitivity, 81.8% (95% CI 70-90); specificity 83% (95% CI 67-93)

likelihood ratio of 4.64Slide34

summarySurvivors and non survivors can be identified earlyImmunosuppression does not workPrevent access to paraquat as outcome is poorSlide35

Poisoning Deaths Transition 2006-2013

Pesticide bans

(

3 years)Slide36

Acknowledgements

Andrew

Dawson, Nick Buckley,

Michael Eddleston,

SACTRC collaborators, research team and hospital staff

University of Peradeniya

Wellcome

Trust &

NHMRCSyngenta

Michael Eddleston1,2,3*, Peter Eyer4, Franz Worek5, Edmund Juszczak6, Nicola Alder6, FahimMohamed2,3, Lalith Senarathna2,3,

Ariyasena

Hittarage7,

Shifa

Azher8, K. Jeganathan7,

Shaluka

Jayamanne8, Ludwig von Meyer9, Andrew H. Dawson3,10, Mohamed

Hussain

Rezvi Sheriff2,3, Nick A.

Buckley3, We thank the Directors and the medical and nursing staff of the study

hospitals for their help and support; Stuart Allen for programming; the

IDMC and Professor Doug Altman for advice; Renate

Heilmair

,

Bodo

Pfeiffer, and Elisabeth

Topoll

for technical assistance; J. V. Peter for

information on the Vellore RCTs; and Allister

Vale and Nick Bateman forcritical review.Ox-Col Poisoning Study Collaborators: Darren Roberts, DamithePitahawatte, Asanga Dissanayaka, Nalinda

Deshapriya

,

Ruwan

Seneviratne

,

Sandima Gunatilake, Indika Weerasinghe, Thushara Diunugala,

Sriyantha

Adikari

,

Suwini

Karunaratne

,

Prabath

Piyasena

,

Senarath

Angammana

,

Deepal

Inguruwatte

,

Samithe

Egodage

,

Mathisha

Dissanayake

,

Waruna

Wijeyasiri-wardene

,

Shammi

Rajapakshe

,

Sidath

Yawasinghe

,

Bandara

,

Sumith

Kumara,

Thushita

Kumara,

Nilumdima

Wijekoon

,

Kusal

Wijeweera

,

Himali

Sepalika

Sudusinghe

,

Hasantha

Ranganath

,

Mahi

Wickramagamage

, R. U.

Wijesinghe

, S. M. I.

Senavirathne

,

Chinthaka

De Silva,

Chaminda

Manamperi

, T.

Suhitharan

,

Sevana-yagam

David, D. Y. Mohamed

Mahir

,

Lakshmi

Sriskandarajah

,

Sellakkuddy

Selva-ganesh

,

Chamila

Bandara

Herath

,

Kanchana

Liyanage

,

Chinthaka

Semasinghe

,

Pandula

Illangasinghe

,

Gayan

Wickramasinghe

,

Sudesh

Rathnayake

, Vindhya

Jayasinghe

,

Iranga

Jayasundara

, Mahesh

Dahanayake

,

Prasanna

Weerakoon

,

Praba

W.

Nanayakkara

,

Paramananthan

Sajeevan, Vethanathan Bavanthan, Janitha Kumari Illangakoon,

Chamantha

Dilmini

Karunarathne

,

Kuleesha

Kodisinghe

,

Buddika

Jeevantha

Wimalarathne

,

Asela

Udagedara

,

Ashoka

Subasinghe

,

Kiloshini

Samanthi

Hendawitharana

,

Dammika

Prabath

Nungamugedara

,

Aruna

Wijayanayaka

,

Sanjeewa

Amarasinghe

,

Sakunthala

Nilmini

Liyanage

,

Indika

de

Alwis

,

Thushara

Priyawansha

,

Chathura

Pallangasinghe

,

Shukry

Zawahir

, Mohamed

Ashrafdeen

Isnan

, and

Syed

Shahmy

Independent Data Monitoring Committee (IDMC): Professor

Mike Clarke (Director, UK Cochrane Centre, Oxford; Chair); Professor

Keith

Hawton

(Department of Psychiatry, Oxford); Dr. Julian Higgins

(MRC Biostatistics Unit, Cambridge University; statistician); Professor

Saroj

Jayasinghe

(Department of Clinical Medicine, Colombo, Sri Lanka);

Professor

Nimal

Senanayake

(Department of Clinical Medicine,

Peradeniya

,

Sri Lanka); Professor Kris

Weerasuriya

(WHO/SEARO, New Delhi).-

Michael

Eddleston

, Edmund

Juszczak

, Nick A Buckley,

Lalith

Senarathna

,

Fahim

Mohamed,

Wasantha

Dissanayake

,

Ariyasena

Hittarage

,

Shifa

Azher

, K

Jeganathan

,

Shaluka

Jayamanne

, M H

Rezvi

Sheriff , David A

Warrell

,

We thank

Palitha

Abeykoon

and Kan

Tun

(WHO),

Lakshman

Karalliedde

,

D G S

Alahakoon

, and W M T B

Wijekoon

, and the Directors, medical

and nursing staff of the study hospitals for their help and support, the

IDMEC, Robin

Ferner

, and Doug Altman for advice, Geoff

Isbister

,

Simon Thomas, Lewis Nelson, and Nick Bateman for critical review, Ly-

Mee

Yu and Nicola Alder for statistical support,

Shukry

Zawahir

, and

Chathura

Palagasinghe

for help with the

fi

nal

patient audit; and the

Ox-Col study doctors for their work in the face of many pressures. ME is a

Wellcome

Trust Career Development Fellow; this work was funded by

grant 063560 from the

Wellcome

Trust’s Tropical Interest Group to ME.

The South Asian Clinical Toxicology Research Collaboration is funded by

a

Wellcome

Trust/National Health and Medical Research Council

International Collaborative Research Grant 071669.

Ox-Col poisoning study collaborators

Darren Roberts,

Asanka

Perera

,

Manjula

Rajapakshe

, K Reginald,

Sapumal Haggalla, Samantha Wijesundara, Jaya Ratnayake,

S M T

Bandara

,

Subashini

Kumarasinghe

,

Manjula

Weerakoon

,

Ayanthi

Karunaratne

,

Manonath

Marasinghe

,

Ruwan

Kumara,

Sumedha Kumara, Nilan Suranga, Jamal Dean, Dharshana Fernando,

Sagara

Kumara,

Koshitha

Gunarathne

, R M

Senanayake

,

Najeeb

Khan,

Kalum

Dhammika

,

Anuradhi

Weerasinghe

, M S F

Zanoona

,

Samanmali

Edirisinghe

,

Medhangi

Karunaratne

,

Sampath

Attapattu

,

Upul

Hendalage

,

Indika

Wanasinghe

, Lal

Bogahawattage

,

SyngentaR

D S M Peiris, S M Dayarathne, Gayan Costa, Chandana de Silva,

Prabath

Abeyrathna

,

Bandula

Senadeera

,

Gayan

Gunarathne

,

Kusal Wijayaweera, M Senthilkumaran, Y Ruthra, K Sutharshan,

Dimuth de Silva, Anjana Amarasinghe, Janaka Balasooriya,

Damithe

Pitahawatte

,

Asangha

Dissanayaka

,

Aravinda

Perera

,

Nalinda

Deshapriya

,

Suranga

Gurusinghe

,

Ruwan

Seneviratne

,

Saman

Chandana

;

Mubashi

Mohamed,

Koshala

Abeysundera

,

Nasmiyar

Mubarak,

Lumbini

de Silva, Daniel,

Sandima

Gunatilake

,

Indika

Weerasinghe

,

Thushara

Diunugala

,

Sriyantha

Adikari

,

Suwini

Karunaratne

,

Prabath

Piyasena

,

Senarath

Angammana

,

Deepal

Inguruwatte

,

Samithe

Egodage

,

Mathisha

Dissanayake

,

Waruna

Wijeyasiriwardene

,

Shammi

Rajapakshe

,

Sidath

Yawasinghe

,

Samanthi

Bandara

,

Sumith

Kumara,

Thushita

Kumara,

Nilumdima

Wijekoon

.

Independent data monitoring and ethics committee

Mike Clarke (Director, UK Cochrane Centre, Oxford; Chair);

Keith

Hawton

(Department of Psychiatry, Oxford); Julian Higgins (MRC

Biostatistics Unit, Cambridge University; Statistician);

Saroj

Jayasinghe

(Department of Clinical Medicine, Colombo);

Nimal

Senanayake

(Department of Clinical Medicine,

Peradeniya

); Kris

Weerasuriya

(WHO/SEARO, New Delhi).Slide37

Other markers of prognosisSlide38

No rise CFR 52.5%Slide39