organophosphoruspoisoningfinal-170803080008.pptx

Organophosphorus poisoning in short

1. OR G ANOP H OSPH O R U S POISONING

2.  Uses  C l assi f ication  Typ e s  M e tabolism and mo d e of abso b ption  Mechanism  C l inical f e a t u re s - nicotinin / muscarni c /ce n tral recep t or and ne u rological:acu t e .IMS. D e l a yed ne u ropathy  Mana g em e nt: diagnosis = ps e udoch o li n e s t e rase n atropine te s t . — dec o ntamination. . atropine . .PAM.. m et a b o l i c co r rection..su p potive e g N a H C O3, Mgso 4 , antiibotics, clonidin e , recom ba c t e rial hy d rolas e s .  Morta l ity

3. INTRO D UC T ION  Organ o phosp h or u s compo u nds a re chemical agen t s in wid e- spread u s e thro u ghout the wor l d, m a inly in agricu l ture .  They are a l so used a s nerve agen t s in chemical warf a re (e.g. Sa r in gas), a nd as therap e utic agen t s, su c h as ecothiopate u s ed in the tre a tment of gla u co m a.  They comprise the ester, ami d e or thiol derivativ e s of phosp h oric acid and are mo s t com m only u sed as p e sticides in co m mercial agric u lture, field sprays and as household c he m i c al s .

4.  There are no r u les a nd r e gulations gov e rning the purc h a s e of these prod u cts, and they a re therefo r e readi l y avai l ab l e “over the co u nt e r ”, despi t e th e m being a major c a use o f mo r bidity and morta l it y .  Exposu r e to o rgan o phosphates in a n at t empt to commit s u icide is a k ey prob l em, particul a rly in the dev e loping co u ntries, and is a mo r e com m on c a use of poisoning than the chronic ex p os u re e x p e ri e nced by fa r mers or sprayers in conta c t with p e sticides.

5. in common use. Th e se are classif i ed acco r di n g to their toxici t y p y r o ph o sp h a tes, p a rathi o n ). Th e se are mai n ly used as coumap h o s , clo r p y rifo s , trichlo r fon ). Th e se are used a s ani m al are used f or househ o ld ap p lica t ion and as field spra y s . CLASSIFICATION  Th e re are mo r e than a h u n d red o r gano p h osp h or u s comp o u n ds and clin i cal use:  1. Highly toxic organ o phos p hates : (e. g . tetr a -eth y l ag r ic u ltural i n sectic i de s .  2. In t ermedi a tely tox i c org an o p hos p hate s : (e.g. i n sectic i des .  3. Low t o xicit y : (e. g . diaz i no n , malathi o n , di c hl o rvo s ). Th e se

6. Types of orga n ophosphate I n se c t i c i d e s N e r v e g a s e s A n t ih e l m in t hi c a g e n t s H e r b i c i d e s Mal a thion Soman Trichlorfon Tri b u f os [ D EF] Par a thion S ar i n Merphos D i azi n on Tab u n Fe n thion VX D i chlorvos Chlo r pyr i fos Eth i on

7. drinking w ater Exp o sure H o m e E x po s u r e O cc u pa t i ona l E x po s u r e O t he r E x po s u r e Accide n tal ingestion F ar m s & F arm w orker Dietary e x posure- Pest i cide re s idu e s on c r ops Lawn and garden use Pest i cide appli c at o r Leaching from soi l s to ground w ater Insect con t rol Manu f acture C o m m unity e x posure F o o d supp l y Mixing and ha n dling Air b orne drift from comme r cial app Wat e r supp l y Lan d s c apers C o ntaminat e d

8. Absorption route  Cuta n eous  Ingestion (Accide n tal O r Suici d al)  Inha l ation  Injection

9. Ph a rmaco k inetics o Most organ o phosp h ates are highly lip i d s o l u ble compo u nds a nd are well absorbed from intact skin, or a l muco u s memb r anes, conjunctiva a nd t he gastrointes t inal and respiratory tracts. o They are rapidly r edistributed to a l l body tissues. o The highest co n centrati o ns a re f o und in the l iver and kidn e ys.

10. .  This high l ipid s o l u bility me a ns th a t they easi l y cr o ss the bl o od / brain bar r ier and th e refore produ c e pot e nt effects on the CNS.  M e taboli s m occurs princi p al l y by oxidation in the liver with conj u gation and es t erase hydro l ysis produ c ing a ha l f-life of m inutes - hou r s.

11. .  The oxidative metabolites of mal a th i on and parathion ( ma l a o xon and para o xo n ) a re a c tive for m s and are s u bsequently hydro l yz e d into inactive metabolites.  Elimin a tion of organo p hos p horus compo u nds a nd its metabolites occ u r m ainly v ia u rine, bile and faeces

12.  . .  A c h E Is An Enzyme T h at D e grades T h e Neu r ot r an s mi t ter A c etylcholi n e ( A c h) Int o Cho l ine  Ach Is Fou n d In C N S & PNS, Ne u ro m us c u l ar mechanism o f action OP I n activate Acetyl Cholines t er a se ( A ch E ) Establis h ment Of A Coval e nt B ond Wi t h A c hE  And A c etic A c id.  Ach I s Fou n d I n C N S & PNS, Ne u ro m us c ul J u nct i ons, And Red Blood Cells (RB C S ) .  Once A c h E - I n activated, A c h A c c u m ul a t e s T h ro u gho u t T h e Nervous S ystem → Oversti m u l at i on Of M u scari n ic And N i coti n ic Rec e p t ors.

13. Once an or g anop h osp h a te bi n ds t o AChE, th e e n z y me can u n dergo o n e of th e followin g : • E n d o g e n o u s h y dr o l y s i s of th e p h osp h oryl a ted enz y me by esteras e s or paraoxo n as e s • Reac ti va ti o n by a st r o n g n u cl e ophi l e such as pra l id o xime ( 2 - PAM) • I rr e ve r s i b le b in d in g and perma n ent enz y me in a cti v a t io n ( ag i n g ) T h e onset and se v erity of symp t oms depend on th e speci f ic compo u n d , amo u n t , r o u t e of exp o su r e, and rate of met a bolic degradation

14. toxic f e atures are us u a l ly ob v ious within 30 m inut e s to 3 and amount of systemic abs o rption. ac c ident a l ing e stion of organophosphorus compounds. co m pound through the gastroint e stin a l, re s piratory tracts Clin i cal fea t ur e s of Org a nophos p hor u s Poisoning  Fo l lowing ex p osure to organophosphorus compounds, the hours.  This may be de l ayed in some cases de p ending on the rate  The majority of pa t ie n ts give a history of int e ntional or  Toxi c ity is pro d uced by the rapid abs o rption of the and skin.

15. dep e nd on the sp e ci f ic a g ent, the q ua n ti t y and the r o u t e of a b dominal p a i n , w h ilst o thers may be u n conscious on ar r i v al make an ea r ly d i agnosis. the  The cli n ical s y mptoms and signs are no n -sp e ci f ic and will en t r y .  S o me p a tie n ts p re s ent with vomit i ng, d i ar r h o ea and at the hos p ital. A high i n dex of suspic i on is th e ref o re needed t o  The cli n ical features can be b r o a dly classif i ed as sec o n d ary to (a) mus c arinic effec t s (b) n icot i n ic ef f ects and (c) c entral rec e pt o r sti m ulation.

16. Cont…  Ear l y ca s es present predominantly with para s ympath e tic ove r -acti v it y , and a c h aracteris t ic garlic smel l .  The end resu l t may be a mu l t i -system manifestation invo l ving the gastroi n testinal, r espirato ry , ca r diova s cu l ar and n e rvo u s systems, as well as involvement o f skele t al mu s cle, other organs and metabolic effects su c h as hy p o - o r hy p erglycemi a .  Most fata l iti e s occur wit h in 24 ho u rs a nd t hose who recover us u a l ly do s o within 10 days.

17. Sympto m s and s igns

18. Who cl a ss i ficat i o n for sever i ty M ILD M ODERATE S E V E R E Seru m/r bc cholin e st e r a s e .8 -2 u / l < . 8 u / l l e v e l 2 -8 u / l Walks a n d ta l ks T a lks wi t h so f t v oice Coma convulsions Abd p a in n aus e a vomit Ca n n o t w a l k profuse b r o n chial he a dache F a sicula t io n s pre se nt s e c r e ti o ns Sali v a t ion sw e a t ing Miosis r e stl e ss ne ss a n xi e ty

19. Cardiac m an i festa t io n s  The c o mmonest car d iac manif e sta t ions fo l lowing poisoning are hypotension (with war m , dilat e d p e ripheri e s), and bradycardi a . Pati e nts s e ldom pre s ent with tachy c ardia and hypert e nsion due to predominant nic o tinic receptor stimula t ion.  C a r d iac manif e sta t ions are oft e n the cause of s e rious co m p l ications and fat a li t y.  E l ectrocar d iog r aphic manif e sta t ions include prolong e d Q - T c int e rva l s, e l e vation of t h e ST s e gm e n t , invert e d T waves and a prolong e d PR int e r v a l . There may also be rh y thm abno r mali t ies such as sin u s b r ady c ardia , ventricu l ar ex t r a - systole s , ventri c u l ar t ac h y c ar d ia and fibrillatio n .

20. toxi c ity fol l o w ing o r ganophosphate poisoning: tone ac t iv i ty i n c l ud i ng AV node blo c kade de pointe s , ventri c ular ta c hycardia and .  L u do m irsky et al described three phas e s of car d iac  Phase I: A brief period of i n crea s ed s y mpathet i c  Phase II: A prolonged period of parasympa t hetic   Phase II I : Q -T prolonga t ion fol l owed by torsade ven t ri c u l ar f i bril l at i on

21. Res p ira t ory man i festa t io n s  Respirato r y m a nifestations of a c u te organ o phosp h or u s poisoning incl u de bronch o rrh o ea, rhinor r hoea, bronch o spasm and l a ryng e al spasm.  This is d u e to the a c tion of the organ o phosp h ate on mu s ca r inic rece p tors.  The inte g rity of the ai r way m a y be compro m ised by e x cessive secr e tions.

22. .  The nicotinic effects lead to weakn e ss and sub s equent para l ysis of respiratory and or o pharyn g eal muscle s .  This inc r eases the likeliho o d o f b o th ai r way obstr u ction and aspiration o f gastric c o nt e nts.  Fina l ly, central neu r o l ogic a l depression m a y le a d to respiratory ar r est

23. Neur o logical man i festations .  Three different ty p es of pa r a l ysis are r ecogniz e d ba s ed l a r gely on the time of oc c u r rence and their differing patho p hysiol o g y :  Type I par a lysis or a c u te para l ysis  Type II para l ysis or Int e rmediate syndro m e  Type III para l ysis or O r ganophosphat e - induced delayed polyneuropathy

24. Type I p a ral y sis or ac u te paralysis  is seen du r ing the initial cholinergic phase.  This is when la r ge nu m bers of b o th mu s ca r inic and nicotinic recep t ors are o cc u pi e d by acetylcholine, leading to p e rsistent de p ol a rization at the neu r o m u s c u l a r junction.  C l inical features incl u de mu s cle fa s c i culation, cra m ps, t witch i ng and weakne s s.  At this stage the p atient may r equire ven t il a tory s u p p o r t d u e to the weakness of the respirat o ry mu s cles l eading to respiratory de p ressi o n and arrest.

25. Type II Pa r alys i s/Intermedi a te syndrome  The int e rm e diate syndrome is a distinct clinical en t ity that occurs 24 to 96 h ours aft e r the in g e s tion of an OP compoun d .  A p pr o xima t e l y 1 - 40% o f p atients treat e d f o r acute po is o ning dev e lop th i s ill n ess.  The onset of the IMS i s o f ten rap i d , w ith pr o gr e ssi o n of mus c le wea k ne s s fr o m the :  o c ular mus c l e s  neck mus c le (t h e patient can n ot raise their h e a d fr o m the p illo w )  proxi m al lim b s  res p irat o ry muscles ( i nt e rcost a ls a n d diap h ra g m) over t he course o f 24 h o urs.

26. hour s , and af f ect con s cious patie n ts without fas c ic u lation or p r oximal limb m u scle w e akness, mani f esti n g as w e akness of features. medical a tte n tion to the o nset of the s y n d r o me. i n nervated by mot o r cranial n erves and decre a sed deep IMS. Cl i nical fea t ure  cli n ical man i festat i ons of IMS ty p ically occur within 24 to 96 oth e r ch o li n er g ic signs.  Mar k ed w e akness of n eck flexion and var y ing de g r e e o f sh o ulder a b d u ct i on and hip flexio n , are the constant cli n ical  Res p irato r y i n su f f i cie n cy is c omm o n and freq u ently dra w s  Other p o ssible man i festat i ons are i n volvement of mus c les ten d on reflex e s.  Sensory imp a irment is n ot a cli n ical man i festat i on of

27. Type III paralysis or org a nophos p ha t e - in d u c ed delay e d polyne u ropath y . (O P IDP)  is a sen s o r y - motor dis t al axonopathy that u s u a l l y occ u rs a fter ing e stion of l arge do s es of an organ o phosp h or u s compo u nd.  The neur o pathy pres e nts as wea k ness and ataxia fo l lowing a latent p e riod of 2 - 4 weeks.  Ini t ial stimu l ation causes excitatory fa s cicu l ation , which th e n progresses to an inhib i tory para l ysis . The ca r dinal symp t oms are distal weakn e ss of the hands and feet.

28. .  This is often preced e d by calf pai n , and in so m e ca s es, para s thesia of the distal part of the limb s . D e l a yed CNS si g ns inc l ude tremo r , anxie t y and com a .

29. MAN A GEMENT D I AGNOSIS  Diagnosis of OP poiso n ing ba s ed o n the H/O e x posure to OP compo u nds, cha r acteristics manifestation o f toxici t iy and improve m ent of s ign and symp t oms after a dministr a tion of a tropin e .  G a r l i c- like s m ell is a n added clinic a l sign especial l y if the pati e nt has in g est e d su l phur c o ntaining OP compo u nd.  This m ay be aided by insi s ting the pati e nt att e ndant to se a rch for a pos s ible poison co n tainer in the vicinity of the pati e nt.

30. Contd.  Ch o linesterase (Ch E ) estimations (pla s ma but y ryl cho l inest e ra s e and red cell ACh E ) are the on l y usef u l biochemic a l to o l for confi r ming e x posure to O P .  Clini c al s e v erity graded on the ba s is of the pseu d ocholinesterase level : -  Mild - 20 - 50% e nzyme a c tivi t y.  Moderate 1 -20% enz y me activit y .  Severe <10% e nzyme activit y . • Tho u gh the enzyme activity does n o t cor r elate well with cli n ic a l severit y .

31. Contd. Plas m a B u tyryl c holi n es t rase R ed ce l l ace t yl c holi n es t rase E a sily a s s a y e d Difficult to a s s a y D o esn ’ t corre l ate we ll w ith n e u r o n al Co rr e l a te we ll w ith n e u r o n al act i v ity ac t i v ity . 30% ac t i v ity – n o r mal muscle f unction < 1 0% ac t i v ity – g r os s ly d e r a n ged muscle f unctio n . Re s p o n s e to a n tido t al the r a p y is l e ss Increased a c t ivity after pralid o xi m e the r a p y. L e v e ls a lt e r e d in mal n ut r iti o n, ch r o n ic L e v e ls a lt e r e d in hemoglobi n o p a t hies ill ne ss, ch r o n ic li v e r dis e a s e a n d a n d thal a ss e mi a . in fe ctio n .

32. Contd.  Ana l yt i cal ident i fication o f OP compo u nd in gastric aspirate or in the body fl u ids gi v es the cl u e that pati e nt has be e n e x posed to OP compo u nd.  However in do u btful ca s es and es p ecial l y if l a bo r ato r y f a cilities a re n o t av a il a ble, 1 mg a tropine can be g iven intravenous l y . If this does not produce marked an t i c holinergic manifesta t ions, an t i c holines t erase poisoning sh o u l d be s t ro n gly s u s p ected.

33. Treatment  D e contamin a tion and Supportive th e rapy  Bl o ckade of Musc a rinic activity with ATRO P IN E .  Rev e rs a l of c holinesterase inhibit i on with OX I M E .  C o rrection of M e tabolic abn o rm a lities  Preven t ion of infection.  Management of complic a tion.

34. De c ontam i nat i on and Su p por t i v e th e r a py  C o mato s e or v o miting pati e nts sho u ld be k e p t in left l a tera l , preferab l y head down position with neck e x t e nsion to reduce the risk of aspirat i on.  Patent airw a y sho u ld be s ecured with placement of airw a y or with e n dotrach e al intu b ation esp e cia l ly if the patient is u nc o nsci o us or h a ving seizu r e.  Frequent su c tioning is essential a s excessive or o pharyn g eal and res p iratory secr e tions may occ l ude the airw a y.  N e ed for oxy g en th e rapy can be a ssessed by frequent as s essment of a rterial oxy g en satu r ation.

35. Contd.  All cloth i ng, h air acc e s s or i es are to be removed and plac e d in app r opriate wa s te bags. The per s on i s to be washed w i th c o p i o u s a mo u nt of wat e r and soap.  Skin folds and undersi d e of fing e rnails and long h ai r s requ i re particul a r att e ntion. Ocular de c ontaminat i on is to be carri e d out by wa s hing e yes with water/nor m al saline.  The health care workers ne e d protect i on through personnel protect i ng equ i pments. R u bb e r Gloves and gowns are re c ommend e d as t h ese compounds are kno w n to penetrate latex / v inyl glo v es.

36. Contd  Ga s tric l a vage  sho u ld be considered in p a ti e nts pres e nti n g w ithin 1 -2 h o urs of ing e st i on of p o iso n .  Ris k s of ga s tric l a v age include a s pira t io n , h y p ox i a, a n d laryng e al s p a s m.  r e du c e d w ith prop e r ma n ag e me n t of a i r w a y .  Activat e d ch a rco a l  r e du c e the p o ison lo a d by a dsorbing it.  I ts e f f icacy has n o t b ee n conclusively pro v e n in hu m a n s.  si n gle to multiple dose act i v a te d cha r co a l is r outi ne ly used in cli n ical practice. ( 25 g m 2 h ou r ly).  AV O I D ca t hartics a n d induced em e si s .

37. n i cot i n i c sympto m s. death : dose regim e n to at t ain targ e t end point s , fol l owed b y found inf e rior to standa r d regimen. atropinis a tion) can be us e d in r e s ource poor s e t ting. Blockade of muscar i nic a c ti v ity w i th a t rop i ne  Sp e cific antidote for muscarinic e f f e cts, no e f fe c t o n  It revers e s li f e t hreat e ning f e at u res that can res u lt in  c e n tral r espir a t o ry d e pres s i o n  b ronch o spasm, e x c essi v e b roncho s ecret io n  se v ere b ra d ycard i a , a nd h y pot e nsi o n .  C u rrent g u ide l in e s recom m end the use of increment a l s e tting up an in f usion t o maintain th e se en d -point s .  Bol u s dose regim e n (2-5 mg atropine ev e ry 1 - 15 min)  Con t inous inf u sion regim e n ( 1 mg/min ti l l fu l l

38. Contd.  T a rget en d -poin t s for Atropine th e rapy :  H e ar t r ate >80/ min.  D i lated p u pil s .  Dry axilla e .  Sy s t o lic b lo o d p r e s s u r e > 80 mm Hg.  C l ear c h e s t on a u s cultati o n with r e s ol u ti o n of br o n c h or r h ea (ab s ence of w h e e ze and c r ept s ). • R e comm e nd e d dose is an in i tial iv bol u s of 1. 8 - 3mg with su b se q u e nt doses dou b l e d ev e ry 5 minut e s if there is no resp o nse or repeat same dose u n til atrop i nization is ach i ev e d. • Mainten a nce dose : 20% o f in i tial atrop i nizing dose per h o ur f o r f i rst 4 8 h o urs a nd grad u a l ly taper over 5 - 10 days, continuously monit o ring the ad e q u acy of therapy.

39. Contd.  Look f or a tropine TO X ICITY  A g it a ti o n, c onfusi o n, hyperth e r m i a , urin a ry retent i on and s e v ere t a c h y c a rd ia .  c a n p r ecip i t a te ischa e mic e v e n ts in pat i e n ts w i th u nd er l y i n g c o ron a ry a rtery d i se a se.  Over atropinis a tion may n e cessi t ate dis c ontin u ation of the atropine inf u sion, fo l low e d b y f requ e nt observation.  When t hey s e tt l e d own t he in f usion is to be start e d a t 7 - 80 % of the previous rat e .  Anticholinergic ag e nt glyc o py r rolate along with at r opine can be us e d in o r d er to limit t he cen t ral stimu l ation produced by atropin e .

40. Contd.  Since gl y copyrrol a te does not en t er CNS in i tial mu s ca r inic signs like coma or dr o wsiness will n o t respond.  It’s use is rec o mmended  w hen there is co p ious s e c r e ti o n a s an adjunct to a t r o p ine  w hen f e a t u r e s of a tropi n e to x icity like de l i r ium e tc are con f used wi t h CNS e f f e cts of poi s on  w hen a t r o p ine is not avail a bl e .  Dose : 7 . 5 mg of glyc o py r ola t e in 2 ml of saline is s t a r t e d as infu s ion and is ti t r ated to the desi r ed effects of dry mucus m embr a ne s .

41. Reversal of cho l inesterase inhibit i on by OXIMES.  Oximes wo r k by r e activ a ting acety l choline s t e rase that has b e e n b ound to the OP m o l e cul e .  Pralidoxime  most f r equ e nt l y used o x i me w o rl d w ide  N u c l e o ph i l ic a gent  o th e r mem b ers inclu d e ob i d o x ime a nd trim edo x i me a nd e x per i ment a l HI 6 and HLO 7.  T h e th e r a peutic window for oximes is limit e d by the time taken for ‘agei n g’ of the e n zym e - OP com p l e x, b e cause ‘aged’ e n zyme can no lo n ger be r eac t ivat e d by oxime s .  M e chanism of action :  Ox i mes get attached to the f r ee an i on i c s ite of the enzyme ChE. The o x i me e n d th e n re a c ts w i th the ph o sphor u s a t o m of OP a tt a c h e d a t the esterat i c site of the enzym e . T h is o x i m e p h os p h a te so formed diffuses a w ay leav i ng the e n z yme in t act (R ea c ti v a ted Ch E ).

42.  Dose :  WHO r e co m mends pralidoxime dose of 30 mg / k g bolus iv o v e r 2 - 30 min f o llo we d by con t inuous i n fusion of 8 m g / k g / h our I n f usion con t inu e d u n t il r e co v e r y : 1 2 h r s a f t e r a t r o p ine h as be e n st o p pe d a n d BC h E n o t e d to incre a s e .  L a r gest ox i mes trial recomm e nds 2gm lo a ding dose fo l lo we d by 5 mg / h r maxim u m for 7 days .  Side effects : Dizziness, headache, b l urr e d vis i on, a n d di p lop i a , are common side ef f ec t s of oxime therapy.  F o rma t i o n of sta b le p h os p h o ryl oximes – h i gh antich o line s te r ase ac t iv i ty.  R a p i d administration may l e ad to tachycardia, l a ryngospasm, mus c le spasm, and tra n sient ne u romuscu l ar b l ockade.

43. Treatment of complic a tion  C a rdiov a sc u l a r complic a tion :  M u scarinic r e ce p tor s timulation cause b r adycar d ia a n d hypot e nsion usually r e s p o n ds to a t r o p in e . Severe hypo te n s ion mi g ht b e n e fit from v a s o p r e ss o r s . The v a l ue of v a s o p r e ss o r s v e r sus hi g her dos e s of a t r o p ine is not y e t cl e ar.  W h ile nico t inic r e ce p tor stimula t ion cause si n us t a chycar d ia a n d hyperte n sion.  ECG c h a n ges: Pr olo n ged Q T c in te rv a l , ST s e g m e nt e le v a t io n , low am p litude T w ave s , e x t r a s ys t ole a n d p r olo n ged PR i n t e rv a l .  Res p irato r y complic a tion :  Regular a n d close obs e rv a t ion in ini t ial cou r se w ill g u ide w hen to v e ntil a t e . Reg u lar suctioning a n d h i g h f low oxygen sho u ld be g i v e n to a l l p a ti e n t s w ith r e s p i r a t ory distre s s. F u r the r , ABG should be done to guide the the r a p y.

44.  Indication of v e n til a tor support : I. Re s p i ra t ory G a s Te n s i o n s i D i rect Indices Ar t erial Ox y g e n Te n s i on < 50 mm Hg on room air Ar t erial C o2 Te n s i on > 50 mm Hg in t he ab s e n ce of m e t abol i c al k alos i s ii D e ri v ed Indices P a o 2 / Fio2 < 250 mm of Hg P A-a O o2 ( Pul m o n a r y a rt eria l -alv e olar O2 gra d i e nt) > 3 5 mm of Hg I I . C l i n ical - Re s p i r at ory Ra t e ( RR)> 35 b rea t hs/ m in I I I. M echanical Indices V ital capa c ity < 15 ml/k g . M a x i m um i n s p ira t ory f o r c e < - 25 cm of H2O.

45.  CNS complicat i on :  P a ti e nts po i son e d w i th o r g a n o ph o sph o r u s fre q u e nt l y d e v e l o p a git a ted d e l ir i um.  T h e c a use i s c o mpl e x, w i th c o ntri b ut i o ns from the pestici d e i tself, a trop i ne t o x i c it y , h y po x i a , a lco ho l i n gested w i th the po i son, a nd me d ical c o mpl i c a ti o ns.  Di a zep a m is fir s t-l i ne th e rapy for se i zur e s; h o w e v e r, se i zur e s a re uncom m on in w e ll o x ygenat e d p at i ents w i th pesti c i d e po i s on i n g. S e iz u res seem to b e more c o mmon w i th o r g a n o pho s pho r u s n e rve agents ( s uch a s som a n a nd t ab u n ).  Anim a l stu d i e s sug g est th a t d i a zep a m re d uces ne u ral da mage a nd pre v e n ts respirat o ry f a i l ure a nd d e a th, b ut stu d i e s in h u mans a re fe w .  G a c ycl id i n e : a nt i -glut a mat e r g ic c o mpo u n d , i nh . S e iz u re c a used by n e rve gas po i s on.  Dose : 10 m g IV slo w ly w h i ch can be repea t ed up to 3 - 40 mg/24 hrs.

46. Supportive tr e atment  Antibiot i c prophylaxis : -  B r oad sp e ct r um an t ibiotics  r isk of in fe ction due to frequ e nt a n d multiple in te rv e n t io n s.  Hydr o ca r bon Aspir a tion : -  ing e st i on of liquid conc e n t r a te s of OP, hyd r oc a r bon so l v e nt as p i r a t ion causes chemi c al p ne u m oniti s .  The s e cas e s are to be ma n ag e d as a ca s e of Acute R e s p i r a t ory Distress Syndrome.  Fur o semide : - It is re c omm e nded if pulmonary o e de m a persi s ts, even after full atropini s atio n .

47.  Magn e sium su l phate :-  blocks ligand- g a te d calcium cha n n el s , r e sulting in re d u c ed ace t yl c holi n e re l ease from pr e -sy n aptic t e rm in al s , thus impro v ing func t ion at n e u r omuscular junc t io n s, and r e du c e d CNS overstimula t ion medi a t e d v ia NM D A r e ce p tor ac t i v a t io n .  I /V Mg S o4 (4g m ) on first day sho w n to decre a se hospi t a l i z a t ion p e r iod a n d i m pro v e outco m e .  C l onidine : -  alpha2-a d rener g ic re c e p tor ag o n ist.  redu c es ace t yl c holi n e sy n t h esis a n d re l ease from pre s y n a p tic t e r min a ls.  A n imal s tudies show be ne fit of clo n idine tre a tm e n t , e s pe cia l ly in combin a ti o n w ith a t r o p in e , but e f fe cts in h uman b e ings are unkno w n.  Dose : 0 . 1 5- . 30 mg i/v bolus f/b . 5 mg o v e r 24hr.

48.  Sodium bi c arb o nate : -  I n c reases in b l o o d pH ( up to 7 ·4 5 – 7·55) h a ve b e en reported to improve o utcome in a n i ma l s thr o ugh a n unkn o w n mech a n i s m .  Useful in ner v e g a s p o i soning.  Dose : 5 meq/kg o v er 1 h o ur f/b 5 -6 meq/kg/ d a y.  The roles of F FP, haemo d ialysis and haemofil t ration are not yet cl e ar.  a recent n on -rand o mised c o ntro l l e d s tu d y in Ch i na sug g ested a b e n ef i t o f h a em o fi l trat i o n a fter po i son i ng w i th d ich lo rvos, w h ich h a s po o r so l u b i l i ty in fat, a nd th e ref o re sh o u l d h a ve a re la ti v e l y s m a ll v o l u me o f d istri b ut i o n.  A sy s tem a tic re v i e w o f th e se th e rap i es in o r g a n o pho s pho r us po i son i ng is u nd er wa y, b ut ran d o mised c o ntro l l e d t r i a ls w i ll b e n e e d ed to esta b l i sh go o d e v i d e n c e - ba sed t r e a tme n t gu id e l i n es.

49.  A bet t er approach than use of butylcho l inest e ra s e might be to give recombin a nt bacterial phosp h otriester a ses o r hydro l ase s .  The s e prot e ins b r e ak do w n or g a n o p hosphor u s p e st i cides e n z yma t ica l ly a n d prot e ct a n imals from p e st i cide p o iso n ing.  Fut ur e clinical development of such e n z ymes co u ld r e d u ce blood conc e n t r a t io n s of or g a n o p hosphor u s , a l lo w ing o p timum ac t i v ity of oth e r tre a tm e n t s.

50. Mechani s m of INTERMEDIATE SX  IMS is well re c ognized as a disorder of t he neuromuscular ju n ctio n ; h o we v e r , its e x a ct u n d e rl y ing m e chanis m s are not cl e ar l y defined.  Sena n aya k e and Kara l liedde in their f irst report of IMS sug g es t ed that the syndrome might be cau s ed by pat h ol o g i c c h ange in t h e p o st s yna p t i c en d - plate re g i o n of striat e d mus c l e s.  Pr o p o sed m e chanism of IMS are:  Dow n r e g u l a ti o n or de se n s iti z a t ion of p o st s y ne p t ic Ach Rec e p t ors.  Pr olo n ged Ach e s t e r a s e inhibiti o n.  Failu r e of pos t syn e ptic Ach rel e as e .  O x ida t i v e str e ss rel a t e d myo p a t h y .  Muscle n e c r osi s .

51. Treatment of IMS  Treatment of IMS is mai n ly s u pportive and th e re are no s p e cific antidotes av a il a ble for this devastating syndro m e.  With sup p orti v e thera p y, r e co v e r y from I MS occu r s 5 –1 8 da y s a f t e r the o n s e t of w e akn e ss.  Reg r e ssion of toxic signs among pati e nts who su r v i v e d I MS follo we d a dis t inct p a t te r n. Mu sc l e po w er first res u med in cra n i a l n erv e -i nn ervated m u sc l es, follo w ed by res p ir a tory mus c l e s, proxi m al mus c l e s, an d n e c k f l exors.

52. Organoph o sphate induced del a yed polyneuropathy (OPIDN )  Occurs 1 - 3 we e k s after acute expo s ure.  U s ually p r esent with sy m pto m s of cra m ping mu s cle p ain followed by num b n e ss and p a r a es t hesia in distal u p per and lower limb.  Can cause foot dro p , w r ist dro p , mu s cle wa s ti n g and deformity such as clawi n g of the hands.  Physical examination :  Symme t rical f lacc i d weakness of the distal mu s cle  V a ri a b l e sensory l oss  Dominant h a nd af f e c t e d mo r e  Tendon reflex a r e lost or reduc e d ; a b sent ankle reflex bei n g a constant featu r e

53. Pathophysio l ogy of OPIDN  N e uropa t hy in d ucing OP co m pounds cause inhibition of ca r b o xylest e rase i.e. NTE (neuropathy t arget e s teras e ).  Inh ib it i o n s hou l d b e irre v ersi b le a nd signif i c a nt.  d eg e n e rat io n o f d i stal regi o ns o f l a r g e, l o ng my e l i n a ted a x o ns a s the primary l e si o n, w h ich progres s es to W a l l er ia n -l i ke d eg e n e rat io n of a ffected fi b er regi o ns.  Inhibition of N T E is n e cessary ant e cedent to OPIDN but precise re l ationship has not be e n defi n ed ti l l n o w.  Physiological f u nction of N T E is not kno w n.  Dic h loro v os and n e r v e agent are not asso c iat e d with OPID N .

54. Treatment  Recov e ry f r om OPIDN is in c omplete a nd may b e limi t ed to t he hands and feets, although substantial functional r ecovery a f t e r 1 - 2 yea r s m a y occur in younger p a ti e n t .  Cu r ren t ly no drug i s a p p roved for treatm e nt of OPIDN.  Followi n g drugs a r e und e r trial :  P he n ylm e thylsul f o n yl fluoride ( P MSF)- s e r ine prot e a s e inhibitor.  Co r ticost e r oid a n d v it a min  Calcium c han n e l blocker  G a nglio s ide mix t u r e

55.  Worldwide Mortality 3-25 % .  Morta l ity Rates Depend O n The  Amount  Del a y In  Del a y In Ingest e d, Disc o very And Tran s port, Intu b ation, And Mortality  Type O f Compound Us e d,  Gen e ral He a lth Of The Patient,  Insufficient R e spiratory Man a gement,  Failure I n We a ning Of f Ventilatory Suppor t .