Mahboob Alam SR Medicine JNMCH AMU Aligarh OR G ANOP H OSPH O R U S POISONING Introduction Chemical agents amide ester or thiol derivatives of phosphoric acid Used as Insecticides ID: 914163
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Slide1
OP AND ALPHOS POISONING
Dr. Md.
Mahboob
Alam
SR- Medicine
JNMCH AMU Aligarh
Slide2OR
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
Slide3CLASSIFICATION
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.
Slide4Routes of absorption
Cutaneous
Ingestion
(Accidental
Or
Suicidal)
Inhalation
Injection
Slide5OP
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.
Slide6Symptoms 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
.
Slide7Nicotinic 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.
Slide8Intoxicated patients may present with tachycardia instead of
bradycardia
due to hypoxia (bronchoconstriction, bronchorrhea).
Cause of Death:
Asphyxia (most common mode)
Cardiovascular collapse
Slide9Diagnosis
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.
Slide10Diagnosis 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
.
Slide11Treatment
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.
Slide12Decontamination 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.
Slide13All
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.
Slide14Gastric
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.
Slide15Slide16Treatment
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.
Slide17Target 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.
Slide18Look 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.
Slide19Reversal 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
.
Slide20COMPLICATIONS
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
Slide21ALPHOS POISONING
Slide22Introduction
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.
Slide23MECHANISM 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
Slide24The
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
Slide25Clinical 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.
Slide26In
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.
Slide27The
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
Slide28Electrocardiographic
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
Slide29Respiratory
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
Slide30Other
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.
Slide31DIAGNOSIS
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
Slide32Laboratory
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.
Slide33MANAGEMENT
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.
Slide34INITIAL
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
Slide35I
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.
Slide36DECREASE
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.
Slide37Potassium
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
.
Slide38HEMODYNAMIC
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).
Slide39The
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
.
Slide40Antacids
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.
Slide41All
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
Slide42Symptomatic
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.
Slide43OTHER
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
Slide44Slide45Slide46PROGNOSTIC
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