nandish jc corrected

8/14/2019 Nandish Jc Corrected

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Mana gement of a cu teana gement of a cu teor ga n op h osphor us p e sti ci der ga n op h osphor us p e sti ci de

poi soni ngoi soni ng

CHAI R PER SON: D R. SA N J AYR. SA N JAYN EER AL G I,EER AL G I,

Author :uthor : Michael Eddleston Nick, BuckleyMD, Peter Eyer MD, and Andrew H

JOURNALOURNAL : L A N C E TL A N C E T[Issue: Volume Feb-08][Issue: Volume Feb-08]


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INTRODUCTION

Organophosphorus pesticide self-poisoningis a major clinical and public-healthproblem across much of rural Asia.

Of the estimated 500 000 deaths from self-harm in the region each year, about 60%are due to pesticide poisoning.

Many studies estimate thatorganophosphorus pesticides areresponsible for around two-thirds of thesedeaths


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xamp es-o organop osp orusrganop osp oruspesti cidesesti cides

, Trichlorfon,Ronnel,

Diazinon,

Malathion,Vapona(dichlorvos,DDVP),

Acephate,

Tetraethyl pyrophosphate,

Phorate,

Parathion,

Phosdrin,

Disulfoton,

Coumophos,

Chlorpyrifos chlorthion

Demethoate

Abate

Naled

Gardone

Dicapthon

Fenitrothion

E P N

Dioxathion

Chlorthion


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BRAND NAMES- organophosphor us pest i c ide srganophosphor us pest i c ide s Sevin Metacid Sufos

Ekalax

Jayalax Hexalux Nuvacron

Rogor Sufos Tik-20

Hinosan Anumet Thimet

Endocron Dimecron


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Pa thophysi ology Organophosphorus pesticides inhibit esterase

enzymes, especially acetylcholinesterase insynapses and on red-cell membranes, andbutyrylcholinesterase in plasma.

.

The subsequent autonomic, CNS, andneuromuscular features of organophosphorus

poisoning are well known


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Clinical features of organophosphorus

pesticide poisoning

Features due to ove rstimulation of mus ca rinicacety lcholine receptors in t he pa rasympathetic sy stem Bronchospasm

Bronchorrhoea

Miosis Lachrymation

Urination

Diarrhoea

Hypotension

Bradycardia

Vomiting

Salivation

Features due to ove rstimulation of nicotinicacety lcholine receptors in t he sympathetic sy stem Tachycardia

Mydriasis

Hypertension

Sweating


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Continued..

Features due to overs timul ati on ofni coti nic and muscari nic acetylchol inereceptors in t he CNS

Confusion

Agitation

Coma

Respiratory failure

Features due to overs timul ati on ofni coti nic acetyl chol ine recept ors at t heneuromuscul ar juncti on Muscle weakness Paralysis

Fasciculations


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INT ERM E D I A T ESYND ROME About 24-96 hours after OP intoxication, followingacute cholinergic crises or while on therapy

Pt is usually conscious develops respiratoryinsufficiency, weakness of external ocular muscles,muscle of mastication, face, soft palate, and is b/l andsymmetrical

Weakness of neck flexion, shoulder abduction and hipflexion

Tendon reflexes are normal are decreased

Sensory system is normal

respiratory insufficiency doveleps over 6 hours


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ORGANOPHOSPHATE

INDUCED DELAYED

POLYNEUROPATHY Weak anticholinestrase activity

Symptoms -1 to 3 weeks

Calf pain, paraesthesias, distel legmuscles, gait ataxia, deep tendon reflexare absent.

Cranial nerves and ANS are normal

Claw hand, foot drop, persistent atrophy,spasticity and ataxia


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CARBAMATES-reversible cholinesterase's inhibitors

Examples

ALDICARB(TEMICK),

AMINOCARB(metacil),

OXAMYL(VYDATE),

ISOLAN(ISOLAN),CARBOFURAN(FURADAN),

METHOMYL(LANNATE),

MEXACARBATE(ZECTRAN),

METHIOCARB(MESUROL),

DIMETILAN(DIMETILAN),

PROPOXUR(BAYGON),

CARBARYL(SEVIN)

Pyrolan


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CLINICAL PRESENTATIONS-

CARBAMATES vs O PCO MPO U N DS Shorter duration of action, more benign

Carbamates poorly penetrates the CNS convulsions are rare with Cc than OPc

Serum and RBC cholinesterase's values are notreliable for confirming the carbamates. As theenzyme activity returns to normal within few hours

Pulmonary edema and respiratory failure areuncommon with carbamates

Recovery from pure carbamate insecticide isgenerally complete


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OR GA NO C HL O R INE IN SE C T IC IDE S

Endrin,

Aldrin

Endosulfan,

Dieldrin,

Toxaphene,

Lindane,BHC,

DDT

Heptachlor,

Kepone,

Terpenepolychlorinates,

Dicofol,

Chlorobengilate,Mirex,

Methoxychlor


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Mechanism of action

-Lindane interfer with axonal

transmission of nerve impulses.

-This slowing results inpropagation of multiple action

potentials for each stimulus


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Clinical presentations

Apprehensions, confusion, dizzziness,seizures, coma, muscle twitching, tremorsparaesthesia, vomiting.

Respiratory failure Cough, wheezing, cyanosis, rales may if

hydrocarbon( vehicle) aspiration hasoccurred

Hepatic and renal compromise,agranulocytosis, aplastic anemia.

Rhabdomyolysis, DIC, lactic acidosis inlindane ingestion


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Chol inester ase assays

Diagnosis of organophosphorus

poisoning should ideally beconfirmed with an assay to

measure butyrylcholinesterase

activity in plasma (oracetylcholinesterase in whole

blood).


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Drawbacks of pl asma butyrylchol ineste rase acti vi tyassays Does not give information about

clinical severity of the poisoning.

Variation between commercialassays can make comparisonsbetween studies difficult.

The concentration ofbutyrylthiocholine varies betweenassays.


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CONTINUED.

Temperature control is

important, because

butyrylcholinesterase activity

increases by some 4% per 1Cincrease in temperature


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Uses of

Butyrylcholinesterase

assays Butyrylcholinesterase assays-

sensitive

Recovery suggests that theorganophosphorus has beeneliminated

Butyrylcholinesterase is produced bythe liver,


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Red cel lacetyl chol inesteras eassays ADVANTAGES

. Red-cell acetylcholinesterase inhibition isa good marker of such inhibition in

synapses and of poisoning severity.

Incubation of an aliquot of blood with alarge quantity of oxime (eg, 100 mol/L

obidoxime) for 15 min before assay willreactivate any acetylcholinesterase thathas not aged.


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Red cel lacetyl chol inesteras eassays (di sadva ntages) Acetylcholinesterase assays are sensitive

to the concentration of oxime andsubstrate, and pH.

Assays with a low substrate concentration,pH 74, and therapeutic oximeconcentrations will reduce backgroundsignal in the assay;

Matrix sulfhydryl compounds in red cells(mainly hemoglobin) react with Ellman'sreagent.


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CONTINUED.. Once red-cell acetylcholinesterase has aged, it only

recovers via erythropoeisis.

Reactions between AChe, OPc and oximes willcontinue if a blood sample is left at room temperatureafter sampling

Blood samples must be diluted and cooled immediatelyafter sampling, to stop the reactions

.

Mixing 200 L of blood freshly drawn into an EDTA tube

with 4 mL of cold saline (at 4C) and then place thesample in a freezer at 20C within 5 min


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Use of butyrylcholinesterase recovery as a marker of

organophosphorus pesticide elimination in (A)

dimethoate and (B) fenthion poisoning


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Summary of treatment Check airway, breathing, and

circulation

.

Record PR,BP, pupil size, presence of

sweat, and auscultatory findings attime of first atropine dose

13 mg of atropine as a bolus,. 09%normal saline; keep the SBP above 80mm Hg and urine output above 05mL/kg/h


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CONTINUED. Give PAM 2 g (or obidoxime 250 mg) IV over

2030 min, infusion of pralidoxime 051 g/h(or obidoxime 30 mg/hr) in 09% NS

5 min after giving atropine, check pulse, bloodpressure, pupil size, sweat, and chest sounds.If no improvement has taken place, givedouble the original dose of atropine

Continue to review every 5 min; give doublingdoses of atropine if response is still absent.


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CONTINUED.

A tachycardia is not a contraindicationto atropine

The pupils will commonly dilate; Delayexists before maximum effect.However, very dilated pupils are anindicator of atropine toxicity

Severe hypotension might benefit fromvasopressors.


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CONTINUED Once the patient is stable, start an infusion of

atropine giving every hour about 1020% of the totaldose needed to stabilise the patient.

stop the infusion and wait 3060 min for these features

to settle before starting again at a lower infusion rate

Continue the oxime infusion until atropine has notbeen needed for 1224 h and the patient has beenextubated

Continue to review respiratory function. Intubate andventilate patients if tidal volume is below 5 mL/kg orvital capacity is below 15 mL/kg, or if they haveapnoeic spells, or PaO2 is less than 8 kPa (60 mm Hg)on FIO2 of more than 60%


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CONTINUED..

Assess flexor neck strength

Any sign of weakness is a sign

that the patient is at risk ofdeveloping peripheral respiratoryfailure (intermediate syndrome).

Tidal volume should be checkedevery 4 h in such patients. Valuesless than 5 mL/kg suggest a needfor intubation and ventilation


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Continued

Treat agitation by reviewing the

dose of atropine being given and

provide adequate sedation with

benzodiazepines.

Monitor frequently for recurring

cholinergic crises due to release

of fat soluble organophosphorusfrom fat stores.

Need retreatment with atro ine


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Factors affecting outcome in

organophosphorus pesticide self-poisoning

Toxicity: rated according to the oralLD50 in rats.

-EX-parathion (LD50 13 mg/kg, WHO:

Class IA) is highly toxic while

temephos (LD50 8600 mg/kg)

Impurities: Pesticide storage in hotconditions can result in chemical

reactions that have toxic products.-Exa-malathion, diazinon and dimethoate


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CONTINUED..

For mul at ion : a pesticide's toxicity will varyaccording to formulation,.

- Alkyl sub-groups : (dimethyl organophosphorus) or

two ethyl groups (diethyl organophosphates)

-Acetylcholinesterase ageing is much faster fordimethyl poisoning than for diethyl poisoning,

therefore to be effective, oximes must be given quicklyto patients with dimethyl poisoning

.A few pesticides have atypical structures, with anotheralkyl group (eg, propyl in profenofos) . These

organophosphorus pesticides age acetylcholinesteraseeven faster and oximes are probably not effective


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CONTINUED

Need fo r activation.Speed o f a ctivation and of A ChEinhibition. The rate of activation of

thioate organophosphates varies

between pesticides.

Duration of e ffect fat solubility andhalf-life. Some fat soluble thioateorganophosphorus pesticides (eg,fenthion) distribute in large amounts tofat stores after absorption.


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CONTINUED..Early cholinergic features are usually mild.

Subsequent slow redistribution and activation

causes recurrent cholinergic features lastingdays or weeks

.

Peripheral respiratory failure is common., sooximes could theoretically be beneficial formany days in such patients.

Other organophosphorus (eg, dichl orvos ) donot need activation, are not fat soluble, and

could have a much more rapid onset of effectand shorter duration of activity.


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Muscari ni c an tagoni st drug s Although atropine remains the mainstay of therapy

worldwide,,

The main adverse-effect of atropine is anticholinergicdelirium in patients who receive too high a dose

Glycopyrronium bromide and hyoscine methobromidedo not enter the CNS.

Some physicians therefore prefer glycopyrronium totreat the peripheral effects of organophosphoruswithout causing confusion.

Its poor CNS penetration suggests that it is ineffectiveat countering coma and reduced respiration seen inpatients with the cholinergic syndrome.


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CONTINUED.

. Hyoscine was used to treat a patient with

severe extra-pyramidal features but fewperipheral signs( inhaled OP nerve agents)

.

A study from south India recorded benefitfrom an infusion of atropine compared with

repeated bolus doses,

Infusions could reduce fluctuations in bloodatropine concentration, reducing the need for

frequent patient observation, an importantbenefit in hospitals with few staff.


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PRALIDOXIME

In particular, two randomised controlledtrials in Vellore, India in the early 1990snoted that low-dose infusions of

pralidoxime might cause harm.

The absense of clinical benefit(suboptimum dose, or bias in allocation).

specific pesticide ingested, the amountingested, or the patients' long delay beforepralidoxime is given.


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CONTINUED

RCT in Baramati, studied the effect of very-high-dose PAM (2 g loading dose, then 1 geither every hour or every 4 h for 48 h, then 1g every 4 h until recovery) in 200 patientswith moderate OP (excluding severely illpatients).

-reduced case fatality (1% vs8%; odds ratio)

- fewer cases of pneumonia (8% vs35%; 016,006039), and

-reduced time on mechanical ventilation(median 5 days vs10 days).


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Acetylcholinesterase was reactivated fully (A) quinalphos, a diethyl

pesticide; partially (B) oxydemeton-methyl, a dimethyl pesticide, or

not at all (C) profenofos, an S-alkyl pesticide by oximes after

poisoning
http://www.sciencedirect.com/science?_ob=MiamiCaptionURL&_method=retrieve&_udi=B6T1B-4PF0XC0-1&_image=B6T1B-4PF0XC0-1-F&_ba=&_user=6032012&_coverDate=02%2F22%2F2008&_rdoc=1&_fmt=full&_orig=search&_cdi=4886&view=c&_isHiQual=Y&_acct=C000054962&_version=1&_urlVersion=0&_userid=6032012&md5=a58e24e28f9ed9c3b90a71e4f642dc09


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BenzodiazepinesDelirium. -pesticide itself,

atropine toxicity, hypoxia,

alcohol ingested with thepoison, and medical

complications

. Acutely agitated patients will

benefit from treatment with

diazepam


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G astroi nt es ti naldecontami nati on

Stabilised and treated with oxygen, atropine, and anoxime.

if the patient arrives within 1 hour of ingesting poison.

Lavage should probably only be considered for patientswho present soon after ingestion of a substantial

amount of toxic pesticide who are intubated, orconscious and willing to cooperate..

A randomised controlled trial in Sri Lanka -No evidencesuggests that patients with pesticide poisoning benefitfrom treatment with activated charcoal.


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Other thera piesMa g n e s iu m s u lp h a t e blocks ligand-gated calcium channels,

-Reduces AChe release from pre-

synaptic terminals

Improves function at NM junctions, and

reduced CNS overstimulation mediated

via NMDA receptor activation.

A trial in people poisoned with OPc

recorded reduced mortalityClon id ine AChe synthesis and releasefrom presynaptic terminals..


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CONTINUED. Sodi um bi carbonat e -used for

treatment of organophosphoruspoisoning in Brazil and Iran, inplace of oximes.[ not usefulaccording to Cochrane review.]

. The roles ofhaemodi al ys isand haemof i l tr ati on NRCTstudy in China -dichlorvos,.


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TREATEMENT FOR ORGANOCHLORINE

INSECTICIDES

SUPPORTIVE Gastroi ntestinaldecontami nati on w ith

superactivated charcoal Seizure-diazepam, lorazepam,

phenobarbital, oxygen, Ivdextrose, thiamine.

Arrythemia-Lidocaine1mg/kgbolus followed by 2to4mg/mincontinous infusion.


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PYRETHRUM(PYRITHRI

N) Examples-Cypermethrin, Prallethrin(Allout)

Symptoms- nausea, vomiting, diarrhea,

hyperexcitability, seizure, tremors, muscleweakness, paralysis, respiratory failure,allergy(dermatitis, asthma, rhinitis,hypersensitivity pneumonitis, anaphylaxis)

,

The course is usually benign

Treatment is supportive


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Concl usi on

Medical management oforganophosphorus pesticidepoisoning is difficult, especially inresource poor locations where mostof these patients present.

Clinical practice is frequently lessthan ideal, with poor initialresuscitation and stabilisation, andpoor use of antidotes.


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P ro g n o s tic Imp o rt a n c e o fro g n o s tic Imp o rt a n c e o fD e fib r ill a to r Sh ocks in P a tie n tse fib r ill a to r Sh ocks in P a tie n tswith He ar t F a ilu reith Hea r t F a ilu reChair person : DR. SANJAY NEERALGIDR. SANJAY NEERALGI,Aut horut hor : Poole, Jeanne E. M.D.; Johnson, George W.

Hellkamp, Anne S. M.S

Jour nal :our nal :LANCETLANCETIssue: Volume 359(10), 4 September 2008, p 10091017


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AIMS OF THE STUDY

Patients with heart failure whoreceive an implantable cardioverter-defibrillator (ICD) for primary

prevention (i.e., prevention of a firstlife-threatening arrhythmic event)may later receive therapeutic shocksfrom the ICD.

Information about long-termprognosis after ICD therapy in suchpatients is limited.


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I n t roduct ion Dilated cardiomyopathy-

Long and short QT syndrome

Hypertrophic cardiomyopathy

Chagas disease

STEMI

Heart failure

VT and VF

f f 40


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Patients with depressed left ventricular function at least 40

days post-STEMI are referred for insertion of an implantable

cardioverter/defibrillator (ICD) if the LVEF is


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Vent ricular tachycardia (V T) (* ) during at rialfibr illation stopped by pacing (#) from animplantable cardioverter defibrillator (ICD) from

recording stored by ICD.. The patient was unaware of

the life-threatening event.


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Cont inued . The Sudden Cardiac Death in Heart Failure

Trial (SCD-HeFT) and the Multicenter

Automatic Defibrillator Implantation Trial II(MADIT II),

Although data from MADIT II previously

showed that patients who receivedappropriate ICD therapy had a risk of deaththat was increased by a factor of 3.

The study assessed the long-term prognostic

significance of both appropriate andinappropriate ICD shocks in SCD- HeFT.


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M e t h o d s SCD-HeFT was a multicenter clinical trial in which

2521 patients with New York Heart Association(NYHA) class II or III heart failure

left ventricular ejection fraction of 35% or less, butno previous sustained ventricular arrhythmia, wererandomly assigned in equal proportions to receivean ICD, amiodarone therapy, or placebo.

The cause of the heart failure was ischemic in

52.0% of the patients and nonischemic in 48.0%.


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CLUSION CRITERIA

patients with New York Heart

Association (NYHA) class II or

III heart failure and a leftventricular ejection fraction of

35% or less, but no previous

sustained ventriculararrhythmia,


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EXCLUSION CRITERIA

The ICD was subsequently removed andnot replaced, owing to complications withthe device, other medical problems orheart transplantation.

Dual-lead ICD at initial implantation Who received a dual-lead ICD or

biventricular ICD as a replacement for theoriginal ICD.

ICD programming included a second zoneof therapy in 64 patients (as well asantitachycardia pacing in 58 of thosepatients).

C ti d


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Continued

Patients whose only detected

events (arrhythmia events

detected at


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ICD Therapy

Each patient in the ICD-therapy group was assigned toreceive a single-lead ICD

This device was implanted in 804 of 811 patients (99.1%);

.

The protocol for the programming of the ICD was that theICD should intervene only for rapid, life-threateningventricular tachycardia or ventricular fibrillation.

A single zone of therapy was used, and an episode oftachycardia was defined as at least 18 of 24 beats at arate of 188 beats per minute or more (


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Electrogram Classification

Shocks were considered to be appropriate if thetriggering rhythm was vt or vf

Inappropriate triggers of ICD shocks included SVT,

oversensing of P or T waves as R waves, doublecounting of R waves, and an artifact from leadfractures or electromagnetic interference.

The delivery of a shock after the spontaneoustermination of nonsustained ventricular tachycardia

was also considered to be inappropriate.


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Results Of the 829 patients who were randomly assigned to

ICD therapy, 811 patients had an ICD implanted,

17 declined to undergo implantation, and 1 died before implantation.

In 31 of the patients in whom an ICD was implanted(3.8%), the ICD was subsequently removed and notreplaced.

Deviations from the protocol occurred in patients whoreceived a dual-lead ICD at initial implantation (3patients.

who received a dual-lead ICD (15) or biventricular ICD

(7) as a replacement for the original ICD.


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Deviations from the protocol with respectto ICD programming included a secondzone of therapy in 64 patients (as well as

antitachycardia pacing in 58 of thosepatients).

The pacing rate was increased in 66patients. (arrhythmia events detected at


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Shocks

The association of shock types with


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the risk of death among patients who

survived at least 24 hours after a first

ICD shock


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Table 2. Time from ICD Shock to Death among Patients Who


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Received at Least One Shock

Discussion


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Discussion This study showed that the occurrence of an

appropriate ICD shock was associated with a markedly

increased risk of death. seen both in patients with IHDand in those with non IHD.

.

Increased risk for patients who receivedinappropriately triggered ICD shocks.

First, patients with heart failure in whom atrialfibrillation develops have been shown to be at anincreased risk for death.

Second, inotropic consequences of the shock itself couldincrease the risk of death, multiple shocks owing to

oversensing or ongoing SVT.

limitations


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limitations The episodes of ICD shock that were

analyzed in this trial may not represent allICD-detected events.

Inability to record sustained rhythms withrates of less than 188 beats per minute,except in the few cases of deviation from theprotocol.

The number of postmortem reports that werecollected was limited, since family membersoften failed to provide notification of apatient's death in time to gather the data.

Limited memory capacity of the device

resulted in overwritten data in patients whohad repetitive arrhythmic events occurringover a short period of time.

l i


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conclusion

in patients with heart failure whoreceive an ICD for primaryprevention, both appropriate and

inappropriate ICD shocks areassociated with a marked increasein the subsequent risk of death,particularly death from progressiveheart failure.

Our results do not establish whatfurther therapies, if any, might beeffective in reducing this risk.


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T H A N KH A N KY O UO U

nandish jc corrected

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