OP AND ALPHOS POISONING Dr. Md. - PowerPoint Presentation

Slide1

OP AND ALPHOS POISONING

Dr. Md.

Mahboob

Alam

SR- Medicine

JNMCH AMU Aligarh

Slide2

OR

G

ANOPHOSPHORUS POISONING

Introduction

Chemical agents: amide, ester or

thiol

derivatives of phosphoric acid

Used as:

Insecticides

Chemical warfare

Therapeutics

No regulations over sale/

puchase

of these compounds

Poisoning is common, accidental/suicidal/homicidal

Slide3

CLASSIFICATION

There are more

than

a

hundred

organophosphorus

compounds

in

common use.

These are

classified according to their toxicity

and

clinical

use:

1.

Highly toxic

organophosphates

: (e.g.

tetra-ethyl pyrophosphates,

parathion

). These are

mainly used

as

agricultural

insecticides.

2.

Intermediately

toxic

organophosphates

: (e.g.

coumaphos

,

clorpyrifos

,

trichlorfon

).

These are

used

as animal

insecticides.

3.

Low

toxicity

:

(e.g.

diazinon

,

malathion

,

dichlorvos

).

These are

used for household

application and as

field

sprays.

Slide4

Routes of absorption

Cutaneous

Ingestion

(Accidental

Or

Suicidal)

Inhalation

Injection

Slide5

OP

in

activate

acetyl

cholines

t

er

a

se

(

A

ch

E

)

.

Ach

E

is

an

enzyme

that

degrades

the

neurotransmitter

acetylcholine

(ach)

into choline

and

acetic

acid.

Ach

is

found

in

CNS

&

PNS,

neuromuscular

junctions,

and

red

blood

cells

(RBCs).

O

nce

A

ch

E

-

inactivated,

Ach

accumulates

throughout

the

nervous

system

→

overstimulation

of

muscarinic

and

nicotinic

receptors.

Slide6

Symptoms and

signs

Muscarinic effects:

SLUDGE

syndrome: S

alivation,

L

acrimation,

U

rination,

D

iarrhea,

G

I

cramping,

E

mesis

.

Bradycardia

,

bronchorrhea

, bronchoconstriction

Other

effects:

Miosis

, diaphoresis

.

Slide7

Nicotinic effects:

Ganglionic:

Tachycardia, hypertension, diaphoresis, mydriasis.

Neuromuscular:

Neuromuscular depolarization,

fasciculations

, motor weakness, paralysis with respiratory failure (analogous to succinylcholine, which is related to

ACh

).

Central:

Confusion, agitation,

lethargy

,

seizures

, coma.

Slide8

Intoxicated patients may present with tachycardia instead of

bradycardia

due to hypoxia (bronchoconstriction, bronchorrhea).

Cause of Death:

Asphyxia (most common mode)

Cardiovascular collapse

Slide9

Diagnosis

Diagnosis of OP poisoning based on

H/O

exposure

to OP compounds,

characteristics

manifestation

of

toxicity

and

improvement of sign

and

symptoms

after

administration

of

atropine.

Garlic-like smell

This

may be

aided

by insisting the patient

attendant

to search for

a

possible poison container

in

the

vicinity

of the

patient.

Slide10

Diagnosis cont’d

Cholinesterase (

ChE

) estimations (plasma

butyryl

cholinesterase

and red

cell

AChE

)

Clinical severity

graded on the basis of

the

pseudocholinesterase

level

:-

Mild

-

20-50%

enzyme

activity.

Moderate

10-20%

enzyme

activity.

Severe <10%

enzyme

activity.

Though the enzyme

activity

does not correlate well with clinical

severity

.

Slide11

Treatment

Decontamination

and

Supportive

therapy

Blockade of Muscarinic

activity

with

ATROPINE.

Reversal of cholinesterase

inhibition

with

OXIME.

Correction of Metabolic

abnormalities

Prevention

of

infection.

Management of

complication.

Slide12

Decontamination and

Supportive

therapy

Comatose or vomiting patients

should

be

kept in

left lateral

, preferably

head down position with

neck

extension to

reduce

the

risk

of

aspirati

on.

Patent

airway should be

secured

with placement of airway or with endotracheal

intubation

especially

if

the patient

is

unconscious or having

seizure.

Frequent

suctioning

is

essential

as

excessive

oropharyngeal

and respiratory

secretions

may

occlude

the airway.

Need for

oxygen

therapy can be

assessed

by frequent assessment of arterial oxygen

saturation.

Slide13

All

clothi

ng, hair accessori

es

are

to be

removed

and

placed

in

appropriate waste bags.

The

person

is

to be

washed with copious amount

of

water

and

soap.

Skin folds

and

underside of fingernails

and

long hairs

require

particular

attention.

Ocular decontamination

is

to be carried out by washing eyes with water/normal

saline.

The

health care workers

need

protection

through personnel protecting

equipments

.

Rubber

Gloves

and

gowns

are

recommended

as

these

compounds

are

known to penetrate latex /vinyl

gloves.

Slide14

Gastric

lavage

should be considered

in

patients presenting

within 1-2 hours

of

ingestion of

poison.

Risks

of gastric lavage

include

aspiration, hypoxia,

and

laryngeal

spasm.

reduced

with

proper

management

of

airway.

Activated

charcoal

reduce the poison load by adsorbing

it.

Its efficacy has

not been

conclusively proven

in

humans.

single to

multiple

dose activated charcoal

is

routinely used

in

clinical

practice.(25gm

2

hourly).

AVOID

cathartics

and induced

emesis.

Slide15

Slide16

Treatment

Specific antidote for muscarinic effects,

no effect

on

nicotinic

symptoms.

It reverses life threatening features

that can

result in

death

:

Current guidelines recommend

the use

of

incremental

dose

regimen

to attain target

end points,

followed

by setting

up an infusion to maintain these

end-points.

Bolus

dose

regimen

(2-5 mg atropine every

10-15

min) found

inferior

to

standard

regimen.

Continous

infusion regimen

( 1 mg/min till full

atropinisation

)

can

be used in

resource poor

setting.

Slide17

Target end-points for

Atropine

therapy

:

Heart

rate >80/

min.

Dilated

pupils.

Dry axillae.

Systolic blood pressure

>80 mm

Hg.

Clear chest

on auscultation

with resolution

of

bronchorrhea

(absence of wheeze

and

crepts

).

Recommended dose

is an initial iv

bolus

of 1-3mg

with subsequent doses doubled every

5 minutes if

there

is no response or repeat

same dose until

atropinization

is

achieved.

Maintenance

dose

: 20%

of

initial

atropinizing

dose per

hour for first

48

hours

and gradually taper over

5

-10 days, continuously

monitoring

the

adequacy of

therapy.

Slide18

Look for atropine

TOXICITY

Agitation,

confusion,

hyperthermia, urinary retention and

severe

tachycardia.

can precipitate

ischaemic

events in

patients

with

underlying

coronary artery

disease.

Over

atropinisation

may necessitate

discontinuation

of the

atropine infusion, followed

by

frequent

observation.

When they settle

down

the infusion is to be

started

at 70-

80 % of

the previous

rate

.

Anticholinergic

agent

glycopyrrolate

along with

atropine can

be used in

order

to

limit

the central stimulation

produced

by

atropine.

Slide19

Reversal of cholinesterase inhibition by OXIMES.

Oximes

work

by

reactivating

acetylcholinesterase

that

has been

bound

to the OP

molecule.

Pralidoxime

most

frequently used

oxime

worldwide

Nucleophilic

agent

The therapeutic window for

oximes

is

limited by the time taken for

‘ageing’

of the

enzyme-OP

complex, because

‘aged’ enzyme

can

no

longer be

reactivated

by

oximes

.

Slide20

COMPLICATIONS

Intermediate

syndrome (IMS):Postacute

paralysis from persistent

ACh

excess after the

acute cholinergic

phase has been controlled.

Weakness

of proximal extremity muscles and muscles supplied by cranial

nerves

that

occurs

hours to days after treatment of acute OP

poisoning and often

leads to

respiratory failure if

unnoticed

OP-induced

delayed neurotoxicity (OPIDN):

Besides

AChE

some OPs also inhibit other neurotoxic

esterases

,

resulting in

polyneuropathy

or spinal cord damage

due to demyelination of the long

nerve fibers

.

OPIDN

usually occurs

several days to weeks after acute

OP

poisoning leading to

temporary, chronic, or recurrent motor or sensory

dysfunctions

TREATMENT: Supportive

Slide21

ALPHOS POISONING

Slide22

Introduction

Aluminum

phosphide (

AlP

)

is

a

cheap,

effective

and

commonly

used

pesticide.

Since

the

first

available report

of

AlP

poisoning

in

the

early

1980s

from

India,

it

is

now one

of

the

most

common

causes

of

poisoning

among

agricultural

pesticides.

Slide23

MECHANISM OF

TOXICITY

Human

toxicity

occurs

either

due

to

the

ingestion

of

AlP

(commonest

mode)

after

exposure

and

injury

from

phosphine

inhalation

(uncommon)

or

even

after

absorption

through

the

skin

(rare).

After

ingestion,

AlP

releases

phosphine

gas

in

the

presence

of

HCl

in

the

stomach

AlP

+

3H2O

→

Al

(OH)3

+

PH3

AlP

+

3HCl

→

AlCl3

+

PH3

Slide24

The

mechanism

of

toxicity

includes

failure

of

cellular

respiration

due

to

the

effect

on

mitochondria,

inhibition

of

cytochrome

C

oxidase

and

formation

of

highly

reactive

hydroxyl

radicals.

There

is

a

decrease

in

the level

of

catalase

and

increase

in

the

activity

of

superoxide

dismutase

in

patients

of

AlP

poisoning

.

Reduction of glutathione concentration

 increased oxidative stress

Slide25

Clinical features

The

signs

and

symptoms

are

nonspecific,

Depend

on

the

dose,

route

of

entry

and

time

lapse

since

exposure

to

poison.

After

inhalation

exposure,

patients

commonly

have

airway

irritation

and

breathlessness.

In

mild

poisoning

nausea,

repeated

vomiting,

diarrhea,

headache,

abdominal

discomfort

or

pain.

Slide26

In

moderate

to

severe

poisoning,

the

signs

and

symptoms

of the

gastrointestinal,

cardiovascular,

respirator

and

nervous

systems

appear

initially

features

of

hepatic

and

renal

failure

and

disseminated

intravascular

coagulation (DIC)

may

also

occur.

Slide27

The

toxicity

of

AlP

particularly

affects

the

cardiac

and

vascular

tissues,

which

manifests

as

Profound and

refractory

hypotension,

congestive

heart

failure,

electrocardiographic

(ECG)

abnormalities,

myocarditis,

subendocardial

infarction

or

pericarditis.

ECG

changes

initial

3

–

6

h:

sinus

tachycardia

is

predominant

6

–

12

h

period:

ST-T

changes

and

conduction

disturbances

appear

later

period,

arrhythmias

occurred

Slide28

Electrocardiographic

changes

following

aluminium

phosphide

poisoning.

(A)

12

‐lead

surface

ECG

recorded

on

admission

showing

sinus

tachycardia.

(B)

ECG

recorded

12

hours

later

showing

extreme

widening

of

the

QRS

complex

Slide29

Respiratory

features

may

include cough,

dyspnoea

,

cyanosis,

pulmonary

edema,

respiratory

failure

and

ARDS.

Metabolic

acidosis

may

be

present

probably due

to

the

accumulation

of

lactic

acid

caused

by blockage

of

oxidative

phosphorylation

and

poor

tissue

perfusion

.

Both

hypo-

and

hypermagnesemia

following

AlP

poisoning have been

described

Slide30

Other

uncommon

findings in

AlP

poisoning

are

intravascular

hemolysis,

acute

adrenocortical

insufficiency,

hepatitis,

acute

tubular

necrosis,

pancreatitis,

hypo-

or

hyperglycemia,

methhemoglobinemia,

microangiopathic

hemolytic

anemia

and

disseminated

intravascular

coagulation.

Slide31

DIAGNOSIS

D

epends

on

the

clinical

suspicion

or

history

(self-report

or by

attendants).

In

case

of

doubt,

diagnosis

can

be

made

easily

by

simple

silver

nitrate-impregnated

paper

test

on

gastric

content

or

on

breath.

G

as

chromatography

with

a

nitrogen

–

phosphorous

detector

is

the

most

specific

and

sensitive

test

and

it

can

be

used

for analysis

of

airtight

samples

Slide32

Laboratory

evaluation

is mainly

done

to

assess

the

prognosis. Leucopenia

indicates

severe

toxicity.

Increased

SGOT

or

SGPT

and

metabolic acidosis

indicate

moderate

to

severe

ingestional

poisoning.

Electrolyte

analysis

shows

decreased

magnesium

potassium

may

be

increased or

decreased.

Measurement

of

plasma

renin

is

significant

as

its

level

in

blood

carries

a

direct

relationship

with

mortality

and

is

raised

in

direct

proportion

to

the

dose

of

pesticide.

The

serum

level

of

cortisol

is

usually

found

to

be decreased

in

severe

poisoning.

Slide33

MANAGEMENT

Management

should

be

started

as soon as

history

and

clinical

examination

support

AlP

poisoning,

and

should

not

be delayed for

the

confirmatory

diagnosis

.

Early

arrival,

resuscitation,

diagnosis,

intensive

monitoring

and

supportive therapy

may

result

in

good

outcome.

Slide34

INITIAL

EVALUATION

AND

RESUSCITATION

E

ffective

oxygenation,

ventilation

and

circulation

.

The

health

care provider

must

take

personal

protection

measures,

including

full

face

mask

and

rubber

gloves

during

decontamination.

A

irway

patency and,

Endotracheal intubation if required

Slide35

I

ntravenous

access

,

preferably

central venous,

to

start

normal

saline

and

vasopressor

therapy

as

appropriate.

Initial

investigation

should

include

ECG,

chest

X-ray,

blood

glucose,

arterial

blood

gas,

electrolytes

including

magnesium,

routine

hemogram,

liver

function

test

renal

function

test.

Repeated

or continuous

ECG

and

echocardiography

can

reveal

cardiac

dysfunction

early.

Slide36

DECREASE

THE

EXPOSURE

OF

POISON

The

victim

should

immediately

be

removed

to

fresh

air.

As

phosphine

is

absorbed

through

the

cutaneous

route,

decontamination

of

skin

and

eyes

must

be

carried

out

thoroughly

with

plain

water

as

early

as

possible

After

ingestion,

effectiveness

of

gut

decontamination

to

reduce

the

absorption

of

unabsorbed

poison

is

primarily

dependent

on

the

duration

of

exposure

of

poison

and

is

useful

if

it

is

done

within

1

–

2

h.

Slide37

Potassium

permanganate

(1:10,000)

is

used

for

gastric

lavage

through a

nasogastric

tube

as

it

oxidises

phosphine

to

nontoxic

phosphate.

Sorbitol

solution

at

a

dose

of

1

–

2

ml/kg

may

be

used as

cathartic.

In

vitro

experimental

findings suggest

that

fat

and

oil,

mainly

vegetable

oils

and

liquid

paraffin,

inhibit

phosphine

release

from

the

ingested

AlP

.

Slide38

HEMODYNAMIC

SUPPORT

Continuous

invasive

hemodynamic

monitoring

and

Early

resuscitation

with

fluid

and

vasoactive

agents.

2-3

litres

of

normal

saline

are

administered

within

the

first

8-12

hr

guided by

central

venous

pressure

(CVP)

and

pulmonary

capillary

wedge

pressure(PCWP).

Slide39

The

aim

is

to

keep

the

CVP

at

around

12-14

cm

of

water.

Some

workers

have

recommended

rapid

infusion

of

saline

(3-6

litres

)

in

the

initial

3

hr.

For

refractory

hypotension,

norepinephrine or phenylephrine could

be

used.

Low

dose

dopamine

(4-6

μg

/kg/min)

is

given

to

keep

systolic

blood

pressure

>90

mm

Hg

.

Slide40

Antacids

and

proton pump

blockers

are

added

for

symptomatic

relief

Phosphine

excretion

can

be increased

by maintaining

adequate

hydration

and

renal

perfusion

with

intravenous

fluids

and

low

dose

(4-6

μg

/kg/min)

dopamine.

Diuretics

like

frusemide

can

be

given

if

systolic

blood

pressure

is

>90

mm

Hg

to

enhance

excretion

as

the

main

route

of

elimination

of

phosphine

is

renal.

Slide41

All

types

of ventricular

arrhythmias

are

seen

in

these patients

and

the

management

is

the

same

as

for

arrhythmias

in

other

situations.

Bicarbonate

level

less

than

15

mEq/L

requires

sodabicarb

in

a

dose

of

50-100

mEq

intravenously

every

8

hour

till

the

bicarbonate

level

rises

to

18-20

mEq/L.

Patients

may

require

up

to

300-500

ml

of

sodium

bicarbonate

.

Dialysis

may

be

required

for

severe

acidosis

and

acute

renal

failure

Slide42

Symptomatic

methemoglobinemia

:

R

equires

antidote

therapy

with

intravenous

methylene blue

(1%

solution)

2

mg/kg of

body

weight

over

5

mins,

which

and

can

be

repeated

if

the

cyanosis

is

not

resolved

.

OTHER

SUPPORTIVE

THERAPY:

The

role

of

magnesium

sulfate

as

a

potential

therapy

in

AlP

poisoning

to

decrease

the

likelihood

of

a

fatal

outcome

has

been

described

Hyperglycemia

at

admission

has

been

found

to

be

a

significant

poor

prognostic

factor.

Therefore,

there

is

a

possible

role

of

treatment

of

hyperglycemia

throughout

management

of the

poisoning, which

may

improve

the

outcome.

Slide43

OTHER

SUPPORTIVE

THERAPY

Many

therapeutic

agents

with

antioxidant properties

have been

tried

in

experimental

animal

studies

with

phosphine

toxicity,

like

n-

acetylcysteine

,

glutathione,

melatonin,

vitamin

C

and

beta

carotene,

but

there

is

a need

for

human

trials

before

their

routine

use

in

AlP

poisoning.

The

possible

role

of

trimetazidine

as

the

treatment

of

cardiovascular

manifestation

has

been

demonstrated,

which is

an

anti-ischemic

drug

that

acts

by

reducing

oxygen

consumption

Slide44

Slide45

Slide46

PROGNOSTIC

INDICES

This

poisoning

has

a

high

mortality (30

–

100%)

and

survival is

unlikely

if

more

than

1.5

g

is

ingested.

The

serum

phosphine

level

of

more

than

1.6

mg/dl

correlates

with

mortality.

Most

of

the

patients

died

within

the

first

24

h

after

ingestion

mainly

due

to

arrhythmia

and

after

24

h

due

to

refractory shock,

acidosis

and

ARDS.

arterial

pH,

serum

bicarbonate

level

and

ECG

abnormalities are

poor

prognostic

factors

Slide47