envenomations1

EnvenomationsEnvenomations

Prof. Dr. Saad S. Al-AniProf. Dr. Saad S. Al-Ani

MBChB, CABP,IBCLCMBChB, CABP,IBCLC

Senior Pediatric ConsultantSenior Pediatric Consultant

Khorfakkan hospitalKhorfakkan hospital

04/11/2304/11/23 Khorfakkan hospital /Sharjah /UAEKhorfakkan hospital /Sharjah /UAE 22

EnvenomationEnvenomation

• is the process by which is the process by which venomvenom is is injected into some animal by the bite injected into some animal by the bite (or sting) of a venomous animal(or sting) of a venomous animal

http://en.wikipedia.org/wiki/Venom_%28poison%29


EnvenomationEnvenomation

• Many kinds of animalsMany kinds of animals, including , including mammalsmammals (e.g., the (e.g., the Northern Short-tailed ShrewNorthern Short-tailed Shrew, , Blarina brevicaudaBlarina brevicauda), ), reptilesreptiles (e.g., the (e.g., the King CobraKing Cobra), ), spidersspiders (e.g., (e.g., Black widowsBlack widows), ), insectsinsects (e.g., (e.g., waspswasps, , honey beeshoney bees and and caterpillarscaterpillars), ), employ venom for hunting employ venom for hunting and for self defenseand for self defense..

• Most venoms are administered by biting Most venoms are administered by biting the skin of the victim the skin of the victim

http://en.wikipedia.org/wiki/Mammal

http://en.wikipedia.org/wiki/Northern_Short-tailed_Shrew

http://en.wikipedia.org/wiki/Reptile

http://en.wikipedia.org/wiki/King_Cobra

http://en.wikipedia.org/wiki/Spider

http://en.wikipedia.org/wiki/Black_widow_spider

http://en.wikipedia.org/wiki/Insect

http://en.wikipedia.org/wiki/Wasp

http://en.wikipedia.org/wiki/Honey_bee

http://en.wikipedia.org/wiki/Caterpillar



•Most bites and stingsMost bites and stings by:- by:-

*Spiders *Spiders

*Snakes *Snakes

*Scorpions, and *Scorpions, and

*Other venomous animals*Other venomous animals

Cause little more than local painCause little more than local pain andand

Do not require medical attentionDo not require medical attention..


Common Common ViperViper

Dice Snake Tessellated Aeskulapian Snake

Green Pit ViperOxus CobraBig Bend Milk Snake


ScorpionScorpionss


SpidersSpiders



ChildrenChildren are at are at greater riskgreater risk for for severe reactions because of their severe reactions because of their smaller volume of distribution for smaller volume of distribution for a given amount of venom.a given amount of venom.



Symptoms of envenomationSymptoms of envenomation may be may be either: either:

1.1.IgE-mediatedIgE-mediated

such as such as anaphylaxisanaphylaxis in response in response

to Hymenoptera stings, orto Hymenoptera stings, or

2.2.Venom-mediatedVenom-mediated

as with the bites of poisonousas with the bites of poisonous

spiders or snakes or the sting ofspiders or snakes or the sting of

scorpionsscorpions



Species-specific antiveninSpecies-specific antivenin

1.1.AmelioratesAmeliorates symptoms and symptoms and

2. 2. PreventsPrevents death from severe death from severe venom-venom-

mediated reactions, mediated reactions,

ButBut the use of antivenin carries the use of antivenin carries

significant risks.significant risks.



VenomsVenoms are are Species-SpecificSpecies-Specific mixtures of:- mixtures of:-

1. 1. Polypeptides Polypeptides

2. 2. Proteolytic enzymesProteolytic enzymes

3.3.GlycoproteinsGlycoproteins, and, and

4. 4. Vasoactive substancesVasoactive substances..



All antiveninsAll antivenins are are animal-derived immunoglobulinsanimal-derived immunoglobulins that that bind bind and and neutralizeneutralize the proteins the proteins in venom. in venom.



The animal origin of The animal origin of antiveninsantivenins exposesexposes patients to large amounts of patients to large amounts of foreign proteinsforeign proteins that may cause both that may cause both

immediateimmediate and and

delayed hypersensitivitydelayed hypersensitivity

reactions.reactions.



In the United StatesIn the United States, ,

onlyonly 4 antivenins4 antivenins are are commercially approved by the U.S. commercially approved by the U.S. Food and Drug Administration (FDA)Food and Drug Administration (FDA)


EnvenomationsEnvenomations1 . 1 . Pit viper bitesPit viper bites - - Horse serum-derived AntiveninHorse serum-derived Antivenin (Crotalidae) Polyvalent (ACP) (Crotalidae) Polyvalent (ACP) --Sheep-derived productSheep-derived product, , Crotalidae Polyvalent Immune Fab Crotalidae Polyvalent Immune Fab

(Crofab)(Crofab)

2. 2. Coral snakeCoral snake (Micrurus fulvius) (Micrurus fulvius) Horse serum–produced antiveninHorse serum–produced antivenin

33.. Black widow spiderBlack widow spider (Latrodectus (Latrodectus mactans)mactans)

Horse serum–produced antiveninHorse serum–produced antivenin



Immediate hypersensitivity reactionsImmediate hypersensitivity reactions to antivenins may beto antivenins may be life-threatening life-threatening, , although the risk varies greatly although the risk varies greatly depending on the product. depending on the product.


Hypersensitivity Hypersensitivity reactionsreactions . . The incidenceThe incidence of such reactions after of such reactions after

administration ofadministration of * * Equine Crotalid antiveninEquine Crotalid antivenin may be as high as may be as high as 25–40%.25–40%. * * Ovine-produced Crofab antiveninOvine-produced Crofab antivenin has a much lower rate of acute has a much lower rate of acute

reactionreaction ((15%15% ), ), * * Black widowBlack widow antiveninantivenin * * Coral snake antiveninCoral snake antivenin both occur at a rate of about both occur at a rate of about 1%.1%.


Hypersensitivity Hypersensitivity reactionsreactions• Given the risk of anaphylaxis, Given the risk of anaphylaxis, antivenin antivenin

should be given only in a setting in which should be given only in a setting in which full resuscitative measuresfull resuscitative measures, including:, including:

* Oxygen, * Oxygen,

* Endotracheal intubation,* Endotracheal intubation,

* Intravenous fluid administration, and* Intravenous fluid administration, and

* Epinephrine,* Epinephrine,

are availableare available..


Hypersensitivity Hypersensitivity reactionsreactions

• Patients Patients should be asked about should be asked about medicationmedication allergiesallergies and previous and previous exposure to antivenins. exposure to antivenins.

• If equine-derived productsIf equine-derived products are to be are to be used, used, skin testingskin testing may be done, but may be done, but the practice remains controversial. the practice remains controversial.



• Skin testingSkin testing

1. Delays treatment 1. Delays treatment

2. Has triggered anaphylaxis and2. Has triggered anaphylaxis and

serum sickness. serum sickness.

3. Has very high false-positive and3. Has very high false-positive and

false-negative rates of up to false-negative rates of up to 30%.30%.



• The The skin testskin test is performed using is performed using 0.02 mL0.02 mL

of a 1:10 dilution of antivenin. of a 1:10 dilution of antivenin.

• A A positive skin test does not preclude positive skin test does not preclude the use of antiveninthe use of antivenin but does but does alert alert the clinician to an increased risk of the clinician to an increased risk of anaphylaxis.anaphylaxis.



• In such instances,In such instances, pretreatment pretreatment with with intravenous administration of intravenous administration of DiphenhydramineDiphenhydramine, 1 mg/kg, and , 1 mg/kg, and MethylprednisoloneMethylprednisolone, 1–2 mg/kg, is , 1–2 mg/kg, is required. required.

• Some toxicologists recommend Some toxicologists recommend pretreatment for all patientspretreatment for all patients receiving antiveninreceiving antivenin



• IfIf signs of immediate hypersensitivity signs of immediate hypersensitivity develop during administration of develop during administration of antivenin, the infusion antivenin, the infusion should be should be stoppedstopped until the patient is stabilized. until the patient is stabilized.



IfIf the severity of envenomation warrants the severity of envenomation warrants continued infusion of antivenin, it may continued infusion of antivenin, it may be:be:

Resumed at a slower rateResumed at a slower rate or or Simultaneously with administrationSimultaneously with administration of epinephrine. of epinephrine.


EnvenomationsEnvenomations• Delayed hypersensitivityDelayed hypersensitivity or or serum serum

sicknesssickness develops: develops:

- In up to - In up to 65%65% of patients who of patients who

receive equine-derived receive equine-derived antiveninantivenin

and and

- In- In15%15% of patients who receive of patients who receive

ovine-derived products. ovine-derived products.


EnvenomationsEnvenomations• Serum sicknessSerum sickness usually develops usually develops 5–215–21

daysdays after exposure and may last for weeks. It is after exposure and may last for weeks. It is most commonly manifestedmost commonly manifested as as 1.Urticaria 1.Urticaria 2.Pruritus 2.Pruritus 3.Arthralgia, and malaise, 3.Arthralgia, and malaise, rarely may presentrarely may present as as 1. Immune complex glomerulonephritis1. Immune complex glomerulonephritis 2. Neuritis or2. Neuritis or 3. Myocarditis 3. Myocarditis



• Intradermal skin testsIntradermal skin tests have not have not been shown to predict the risk of been shown to predict the risk of serum sickness accurately.serum sickness accurately.

• Prophylactic use of antihistamines Prophylactic use of antihistamines and corticosteroidsand corticosteroids may reduce the may reduce the risk of serum sickness and definitely risk of serum sickness and definitely is of benefit if symptoms develop.is of benefit if symptoms develop.


SNAKEBITESNAKEBITE

• Of the >3,000 known species of snakes, Of the >3,000 known species of snakes, only 200 are poisonous to humans. Of only 200 are poisonous to humans. Of poisonous snakes, poisonous snakes, 90%90% are members of are members of one one of threeof three familiesfamilies::

1. the 1. the HydrophidaeHydrophidae, or poisonous sea , or poisonous sea snakes; snakes;

2.the 2.the ElapidaeElapidae, which includes the cobras,, which includes the cobras, mambas, and coral snakes; and mambas, and coral snakes; and 3.the 3.the ViperidaeViperidae, or true vipers , or true vipers


• In the U.S., In the U.S., 95%95% of poisonous snakebites of poisonous snakebites are inflicted by the are inflicted by the Crotalidae, or pitCrotalidae, or pit vipersvipers, which are a subfamily of the true , which are a subfamily of the true vipers. Pit vipers may be identified by vipers. Pit vipers may be identified by their:their:

* * Triangular headsTriangular heads

* * Elliptical eyesElliptical eyes, and, and

* * Identifiable pit between the eyes andIdentifiable pit between the eyes and

nose nose

SNAKEBITESNAKEBITE


SNAKEBITESNAKEBITE

• Members of the pit viper familyMembers of the pit viper family in the in the U.S. include:U.S. include:

1. 1. rattlesnakes rattlesnakes

2. 2. cottonmouthscottonmouths, and, and

3. 3. copperheadscopperheads..


SNAKEBITESNAKEBITE

• Coral snakesCoral snakes, the other poisonous snakes , the other poisonous snakes native to the U.S., are found in Texas and native to the U.S., are found in Texas and the Southeast and are members of the the Southeast and are members of the Elapidae family. Elapidae family.

• Coral snakesCoral snakes are small with : are small with :

* * Small, rounded headSmall, rounded head and and

* * Brightly colored bands of Brightly colored bands of blackblack and and redred

separated by more narrow separated by more narrow yellowyellow bands bands. .


SNAKEBITESNAKEBITE

The rhyme “The rhyme “redred on on yellowyellow, , killkill a a fellowfellow; ; redred on on blackblack, , venom lackvenom lack” ” serves to differentiate the coral serves to differentiate the coral snake from the similar-appearing but snake from the similar-appearing but nonpoisonous scarlet king snake. nonpoisonous scarlet king snake.


SNAKEBITESNAKEBITE

• CobrasCobras and and kraitskraits

are common in parts of Asia are common in parts of Asia

• whereas whereas vipersvipers, , cobrascobras, and , and addersadders

are common in parts of Africa.are common in parts of Africa.

• CobrasCobras and and kraitskraits

are common in parts of Asia are common in parts of Asia

• whereas whereas vipersvipers, , cobrascobras, and , and addersadders

are common in parts of Africa.are common in parts of Africa.


EpidemiologyEpidemiology• The incidence of snakebites is;The incidence of snakebites is;

• HigherHigher in in

--AfricaAfrica

* * 5 bites per1000 persons5 bites per1000 persons in in NigeriaNigeria

* * 2300023000 snake bites snake bites deathsdeaths per year per year

in West Africa in West Africa

- - AustraliaAustralia

0.6 to 5 bites per 10000.6 to 5 bites per 1000

- - AsiaAsia

- - South AmericaSouth America


Epidemiology (cont.)Epidemiology (cont.)

• In USAIn USA ,most snakebites occur in ,most snakebites occur in young males and involve alcohol young males and involve alcohol intoxication; often the victim had intoxication; often the victim had tried to capture or play with snake.tried to capture or play with snake.

• In AfricaIn Africa and and AsiaAsia most bites occur most bites occur on lower limbs ,at night ,and on lower limbs ,at night ,and provoked by stepping on a snake provoked by stepping on a snake


Epidemiology (cont.)Epidemiology (cont.)

• In USAIn USA

there are there are only 12 -15 deaths eachonly 12 -15 deaths each yearyear

• In parts of In parts of AfricaAfrica and and AsiaAsia

where as where as case fatality ratescase fatality rates up to up to 15%15% are reported among hospitalized victims are reported among hospitalized victims of snakebites where intensive care and of snakebites where intensive care and antivenom access are limitedantivenom access are limited


PathogenesisPathogenesis

• Snake venomSnake venom is a mixture of; is a mixture of;

-Polypeptides-Polypeptides

-Proteolytic enzymes-Proteolytic enzymes

-Toxins (species-specific)-Toxins (species-specific)


PathogenesisPathogenesis (cont.) (cont.)

• VenomVenom of the of the Elapidae Elapidae and the and the HydrophidaeHydrophidae is is primarily neurotoxicprimarily neurotoxic and has and has a curare- like effecta curare- like effect by by blocking neurotransmission at the blocking neurotransmission at the neuromuscular junctionneuromuscular junction

• DeathDeath results from results from respiratory respiratory depressiondepression


PathogenesisPathogenesis (cont.) (cont.)

• CrotalidaeCrotalidae venomvenom is is cytolytic cytolytic ,causing ,causing

1. tissue necrosis1. tissue necrosis

2. vascular leak2. vascular leak

3.coagulopathies3.coagulopathies

• DeathDeath from from pit viper bitespit viper bites results from: results from:

1. hemorrhagic shock1. hemorrhagic shock

2.adult respiratory distress syndrome 2.adult respiratory distress syndrome

3. renal failure3. renal failure


Clinical manifestationsClinical manifestations

• Pit viper bitesPit viper bites

-occur usually -occur usually on the extremitieson the extremities

- - painpain and and swellingswelling occur at the site occur at the site

within minuteswithin minutes

- as the venom moves proximally ,- as the venom moves proximally ,edemaedema

and and ecchymosisecchymosis advance advance

- - in severe casesin severe cases , ,bullabulla formation and formation and tissuetissue

necrosisnecrosis ensue ensue


Clinical manifestations Clinical manifestations (cont.)(cont.)• Pit viper bites (cont.)Pit viper bites (cont.) --systemic symptoms includesystemic symptoms include;; * * nausea, vomitingnausea, vomiting * * diaphoresisdiaphoresis * * weaknessweakness * * tingling around the facetingling around the face **muscle fasciculationmuscle fasciculation

Gold BS,Dart RC, Barish RA: bites of venomous snakes, N Gold BS,Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356Engl J Med 2002;347:347-356


Clinical manifestations Clinical manifestations (cont.)(cont.)• Pit viper bites (cont.)Pit viper bites (cont.)

* * Rarely .may present with :Rarely .may present with :

# # generalized edemageneralized edema

# # cardiac arrhythmiascardiac arrhythmias

# # complex clotting complex clotting abnormalitiesabnormalities

Gold BS,Dart RC, Barish RA: bites of venomous snakes, N Engl Gold BS,Dart RC, Barish RA: bites of venomous snakes, N Engl

J Med 2002;347:347-356J Med 2002;347:347-356


Clinical manifestations Clinical manifestations (cont.)(cont.)

The coral snakes bitesThe coral snakes bites

• Bites of most Elapidae, including the coral snakes Bites of most Elapidae, including the coral snakes are are minimally painfulminimally painful because the venom has because the venom has no no

cytotoxincytotoxin• LackLack of immediate symptoms of immediate symptoms should not be should not be

mistakenmistaken for the absence of serious envenomation for the absence of serious envenomation -- Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med

2002;347:347-3562002;347:347-356


Clinical manifestations Clinical manifestations (cont.)(cont.)

• The venom of the coral snake is primarilyThe venom of the coral snake is primarily neurotoxicneurotoxic , ,and and symptoms can progress rapidlysymptoms can progress rapidly in a few hoursin a few hours

from from mild drowsinessmild drowsiness to to cranial nerve palsiescranial nerve palsies weaknessweakness andand death from respiratory failuredeath from respiratory failure

Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356


TreatmentTreatment • First: First: determinedetermine whether the bite was by a whether the bite was by a

poisonous snake and if envenomation poisonous snake and if envenomation occurred occurred

• Immediate careImmediate care is to is to immobilizeimmobilize the the bitten extremity and bitten extremity and transporttransport the patient the patient quickly to the nearest hospital If the bite is quickly to the nearest hospital If the bite is determined to be from a venomous snake determined to be from a venomous snake

Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356Engl J Med 2002;347:347-356


TreatmentTreatment

• Avoid applying of ice to the bite site or Avoid applying of ice to the bite site or using excision and suction as it is believed using excision and suction as it is believed to cause more tissue damage than benefitto cause more tissue damage than benefit

• Many experts now eschew any constricting Many experts now eschew any constricting bands because of the risk of ischemiabands because of the risk of ischemia

Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Gold BS, Dart RC, Barish RA: bites of venomous snakes, N

Engl J Med 2002;347:347-356Engl J Med 2002;347:347-356


TreatmentTreatment • On arrival at the emergency department On arrival at the emergency department 1. a large-bore i.v line should be inserted1. a large-bore i.v line should be inserted 2. initial blood tests should include;2. initial blood tests should include; i. type and cross match’i. type and cross match’ ii. Complete blood cell and platelets countsii. Complete blood cell and platelets counts iii. Prothrombine and partial thromboplastin timesiii. Prothrombine and partial thromboplastin times iv. Fibrinogen and fibrin degradation products’iv. Fibrinogen and fibrin degradation products’ v. Blood urea nitrogen ,creatinine, and creatine v. Blood urea nitrogen ,creatinine, and creatine

phosphokinase levelphosphokinase level

these investigations must be repeated at intervals depending these investigations must be repeated at intervals depending on severity of envenomationon severity of envenomation

Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356


TreatmentTreatment

• baseline vital signs and measurement of baseline vital signs and measurement of

circumference of the bitten extremity circumference of the bitten extremity should be obtained and demarcation of should be obtained and demarcation of 3eccyhmosis and swelling should be marked 3eccyhmosis and swelling should be marked on the limb on the limb

• The wound should be cleansed and tetanus The wound should be cleansed and tetanus toxoid given if appropriatetoxoid given if appropriate

Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Gold BS, Dart RC, Barish RA: bites of venomous snakes, N

Engl J Med 2002;347:347-356Engl J Med 2002;347:347-356


TreatmentTreatment

Usage of antiveninUsage of antivenin It depends on the It depends on the severityseverity and and progressionprogression of of

symptoms symptoms • RattlesnakeRattlesnake envenomation requires envenomation requires

antiveninantivenin• Copperhead Copperhead bites do notbites do not • Cottonmouth Cottonmouth bites fall between these bites fall between these

extremesextremes

Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-3562002;347:347-356


GradeGrade Features Features

Grade 0Grade 0 No envenomationNo envenomation

Grade 1Grade 1 Minimal envenomation Minimal envenomation

(local swelling and pain without (local swelling and pain without progression)progression)

The severity of envenomationThe severity of envenomation

is commonly graded on a 4 –point scaleis commonly graded on a 4 –point scale


GradeGrade Features Features

Grade 2Grade 2 Moderate envenomation Moderate envenomation

(swelling ,pain , or ecchymosis (swelling ,pain , or ecchymosis progress beyond the site of injuryprogress beyond the site of injury

Mild systemic or laboratory Mild systemic or laboratory manifestations)manifestations)

Grade 3Grade 3

Severe envenomationSevere envenomation

(marked local response ,severe (marked local response ,severe systemic findings and significant systemic findings and significant alteration in laboratory findingsalteration in laboratory findings

The severity of envenomation The severity of envenomation (Cont,) (Cont,)


AntiveninAntivenin

• Is most effective if delivered within 4 Is most effective if delivered within 4 hr of the bite hr of the bite

• Is of little value if administration is Is of little value if administration is delayed beyond 12 hrdelayed beyond 12 hr

• Poses a small ,but significant risk of Poses a small ,but significant risk of an immediate hypersensitivity an immediate hypersensitivity reactionreaction


AntiveninAntivenin

• Antivenin (Crotalidae) Polyvalent Antivenin (Crotalidae) Polyvalent - is administered in increments of 5 vials and - is administered in increments of 5 vials and

repeated every 2hr as needed to neutralize repeated every 2hr as needed to neutralize circulating venom, as measured by;circulating venom, as measured by;

- normalization of clotting parameters- normalization of clotting parameters - A halt in the progression of swelling of the - A halt in the progression of swelling of the

affected limbaffected limb - children often require more antivenin than - children often require more antivenin than

a similarly envenomated adult because of a similarly envenomated adult because of their small volume-to venom ratiotheir small volume-to venom ratio


Thank youThank you

envenomations1

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