Envenomations Prof. Dr. Saad S. Al-Ani MBChB, CABP,IBCLC Senior Pediatric Consultant Khorfakkan hospital
Envenomation <ul><li>is the process by which  venom  is injected into some animal by the bite (or sting) of a venomous ani...
Envenomation <ul><li>Many kinds of animals , including  mammals  (e.g., the  Northern Short-tailed Shrew ,  Blarina brevic...
Envenomations <ul><li>Most bites and stings  by:-  </li></ul><ul><li>*Spiders  </li></ul><ul><li>*Snakes  </li></ul><ul><l...
Common Viper Dice Snake Tessellated Aeskulapian Snake Green Pit Viper Oxus Cobra Big Bend Milk   Snake
Scorpions
Spiders
Envenomations <ul><li>Children  are at  greater risk  for severe reactions because of their smaller volume of distribution...
Envenomations <ul><li>Symptoms of envenomation  may be either:  </li></ul><ul><li>1. IgE-mediated   </li></ul><ul><li>such...
Envenomations <ul><li>Species-specific antivenin   </li></ul><ul><li>1. Ameliorates  symptoms and </li></ul><ul><li>2.  Pr...
Envenomations <ul><li>Venoms   </li></ul><ul><li>are  Species-Specific  mixtures of:- </li></ul><ul><li>1.  Polypeptides  ...
Envenomations <ul><li>All antivenins   </li></ul><ul><li>are  animal-derived immunoglobulins </li></ul><ul><li>that  bind ...
Envenomations <ul><li>The animal origin of  antivenins   exposes   patients to large amounts of  foreign proteins  that ma...
Envenomations <ul><li>In the United States ,  </li></ul><ul><li>only   4 antivenins  are commercially approved by the U.S....
Envenomations <ul><li>1 .  Pit viper bites   </li></ul><ul><li>-  Horse serum-derived Antivenin </li></ul><ul><li>(Crotali...
Envenomations <ul><li>Immediate hypersensitivity reactions   to antivenins may be  life-threatening , although the risk va...
Hypersensitivity reactions <ul><li>.  The incidence  of such reactions after administration of </li></ul><ul><li>*  Equine...
Hypersensitivity reactions <ul><li>Given the risk of anaphylaxis,  antivenin should be given only in a setting in which fu...
Hypersensitivity reactions <ul><li>Patients  should be asked about medication   allergies  and previous exposure to antive...
Hypersensitivity reactions <ul><li>Skin testing </li></ul><ul><li>1. Delays treatment  </li></ul><ul><li>2.  Has triggered...
Hypersensitivity reactions <ul><li>The  skin test  is performed using 0.02 mL </li></ul><ul><li>of a 1:10 dilution of anti...
Envenomations <ul><li>In such instances,  pretreatment  with intravenous administration of  Diphenhydramine , 1 mg/kg, and...
Envenomations <ul><li>If  signs of immediate hypersensitivity develop during administration of antivenin, the infusion  sh...
Envenomations <ul><li>If  the severity of envenomation warrants continued infusion of antivenin, it may be: </li></ul><ul>...
Envenomations <ul><li>Delayed hypersensitivity  or  serum sickness   develops: </li></ul><ul><li>- In up to  65%  of patie...
Envenomations <ul><li>Serum sickness  usually develops  5–21   days </li></ul><ul><li>after exposure and may last for week...
Envenomations <ul><li>Intradermal skin tests  have not been shown to predict the risk of serum sickness accurately. </li><...
SNAKEBITE <ul><li>Of the >3,000 known species of snakes, only 200 are poisonous to humans. Of poisonous snakes,  90%  are ...
<ul><li>In the U.S.,  95%  of poisonous snakebites are inflicted by the  Crotalidae, or pit   vipers , which are a subfami...
SNAKEBITE <ul><li>Members of the pit viper family  in the U.S.  include: </li></ul><ul><li>1.  rattlesnakes  </li></ul><ul...
SNAKEBITE <ul><li>Coral snakes , the other poisonous snakes native to the U.S., are found in Texas and the Southeast and a...
SNAKEBITE <ul><li>The rhyme “ red  on  yellow ,  kill   a fellow ;  red  on  black ,  venom lack ” serves to differentiate...
SNAKEBITE <ul><li>Cobras  and  kraits   </li></ul><ul><li>are common in parts of Asia  </li></ul><ul><li>whereas  vipers ,...
Epidemiology <ul><li>The incidence of snakebites is; </li></ul><ul><li>Higher  in  </li></ul><ul><li>- Africa </li></ul><u...
Epidemiology (cont.) <ul><li>In USA  ,most snakebites occur in young males and involve alcohol intoxication; often the vic...
Epidemiology (cont.) <ul><li>In USA   </li></ul><ul><li>there are  only 12 -15 deaths each   year   </li></ul><ul><li>In p...
Pathogenesis <ul><li>Snake venom  is a mixture of; </li></ul><ul><li>-Polypeptides </li></ul><ul><li>-Proteolytic enzymes ...
Pathogenesis  (cont.) <ul><li>Venom  of the  Elapidae  and the  Hydrophidae  is  primarily neurotoxic  and has  a curare- ...
Pathogenesis  (cont.) <ul><li>Crotalidae   venom  is  cytolytic  ,causing  </li></ul><ul><li>1. tissue necrosis </li></ul>...
Clinical manifestations <ul><li>Pit viper bites   </li></ul><ul><li>-occur usually  on the extremities </li></ul><ul><li>-...
Clinical manifestations (cont.) <ul><li>Pit viper bites (cont.) </li></ul><ul><li>- systemic symptoms include ; </li></ul>...
Clinical manifestations (cont.) <ul><li>Pit viper bites (cont.) </li></ul><ul><li>*  Rarely .may present with : </li></ul>...
Clinical manifestations (cont.) <ul><li>The coral snakes bites </li></ul><ul><li>Bites of most Elapidae, including the cor...
Clinical manifestations (cont.) <ul><li>The venom of the coral snake is primarily   neurotoxic  , and symptoms can progres...
Treatment <ul><li>First:  determine  whether the bite was by a poisonous snake and if envenomation occurred  </li></ul><ul...
Treatment <ul><li>Avoid applying of  ice to the bite site or using excision and suction as it is believed to cause more ti...
Treatment <ul><li>On arrival at the emergency department  </li></ul><ul><li>1. a large-bore i.v line should be inserted </...
Treatment <ul><li>baseline vital signs  and measurement of circumference of the bitten extremity should be obtained and de...
Treatment <ul><li>Usage of antivenin   </li></ul><ul><li>It depends on the  severity  and  progression  of symptoms  </li>...
The severity of envenomation is commonly graded on a 4 –point scale   Minimal envenomation  (local swelling and pain witho...
The severity of envenomation  (Cont,)  Severe envenomation (marked local response ,severe systemic findings and significan...
Antivenin <ul><li>Is most effective if delivered within 4 hr of the bite  </li></ul><ul><li>Is of little value if administ...
Antivenin <ul><li>Antivenin (Crotalidae) Polyvalent  </li></ul><ul><li>- is administered in increments of 5 vials and repe...
<ul><li>Thank you </li></ul>
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Envenomations1

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Envenomations1

  1. 1. Envenomations Prof. Dr. Saad S. Al-Ani MBChB, CABP,IBCLC Senior Pediatric Consultant Khorfakkan hospital
  2. 2. Envenomation <ul><li>is the process by which venom is injected into some animal by the bite (or sting) of a venomous animal </li></ul>
  3. 3. Envenomation <ul><li>Many kinds of animals , including mammals (e.g., the Northern Short-tailed Shrew , Blarina brevicauda ), reptiles (e.g., the King Cobra ), spiders (e.g., Black widows ), insects (e.g., wasps , honey bees and caterpillars ), employ venom for hunting and for self defense . </li></ul><ul><li>Most venoms are administered by biting the skin of the victim </li></ul>
  4. 4. Envenomations <ul><li>Most bites and stings by:- </li></ul><ul><li>*Spiders </li></ul><ul><li>*Snakes </li></ul><ul><li>*Scorpions, and </li></ul><ul><li>*Other venomous animals </li></ul><ul><li>Cause little more than local pain and </li></ul><ul><li>Do not require medical attention . </li></ul>
  5. 5. Common Viper Dice Snake Tessellated Aeskulapian Snake Green Pit Viper Oxus Cobra Big Bend Milk Snake
  6. 6. Scorpions
  7. 7. Spiders
  8. 8. Envenomations <ul><li>Children are at greater risk for severe reactions because of their smaller volume of distribution for a given amount of venom. </li></ul>
  9. 9. Envenomations <ul><li>Symptoms of envenomation may be either: </li></ul><ul><li>1. IgE-mediated </li></ul><ul><li>such as anaphylaxis in response </li></ul><ul><li>to Hymenoptera stings, or </li></ul><ul><li>2. Venom-mediated </li></ul><ul><li>as with the bites of poisonous </li></ul><ul><li>spiders or snakes or the sting of </li></ul><ul><li>scorpions </li></ul>
  10. 10. Envenomations <ul><li>Species-specific antivenin </li></ul><ul><li>1. Ameliorates symptoms and </li></ul><ul><li>2. Prevents death from severe venom- </li></ul><ul><li>mediated reactions, </li></ul><ul><li>But the use of antivenin carries </li></ul><ul><li>significant risks. </li></ul>
  11. 11. Envenomations <ul><li>Venoms </li></ul><ul><li>are Species-Specific mixtures of:- </li></ul><ul><li>1. Polypeptides </li></ul><ul><li>2. Proteolytic enzymes </li></ul><ul><li>3. Glycoproteins , and </li></ul><ul><li>4. Vasoactive substances . </li></ul>
  12. 12. Envenomations <ul><li>All antivenins </li></ul><ul><li>are animal-derived immunoglobulins </li></ul><ul><li>that bind and neutralize the proteins </li></ul><ul><li>in venom. </li></ul>
  13. 13. Envenomations <ul><li>The animal origin of antivenins exposes patients to large amounts of foreign proteins that may cause both </li></ul><ul><li>immediate and </li></ul><ul><li>delayed hypersensitivity </li></ul><ul><li>reactions. </li></ul>
  14. 14. Envenomations <ul><li>In the United States , </li></ul><ul><li>only 4 antivenins are commercially approved by the U.S. Food and Drug Administration (FDA) </li></ul>
  15. 15. Envenomations <ul><li>1 . Pit viper bites </li></ul><ul><li>- Horse serum-derived Antivenin </li></ul><ul><li>(Crotalidae) Polyvalent (ACP) </li></ul><ul><li>- Sheep-derived product , </li></ul><ul><li>Crotalidae Polyvalent Immune Fab (Crofab) </li></ul><ul><li>2. Coral snake (Micrurus fulvius) </li></ul><ul><li>Horse serum–produced antivenin </li></ul><ul><li>3 . Black widow spider (Latrodectus mactans) </li></ul><ul><li>Horse serum–produced antivenin </li></ul>
  16. 16. Envenomations <ul><li>Immediate hypersensitivity reactions to antivenins may be life-threatening , although the risk varies greatly depending on the product. </li></ul>
  17. 17. Hypersensitivity reactions <ul><li>. The incidence of such reactions after administration of </li></ul><ul><li>* Equine Crotalid antivenin </li></ul><ul><li>may be as high as 25–40%. </li></ul><ul><li>* Ovine-produced Crofab antivenin </li></ul><ul><li>has a much lower rate of acute reaction </li></ul><ul><li>( 15% ), </li></ul><ul><li>* Black widow antivenin </li></ul><ul><li>* Coral snake antivenin </li></ul><ul><li>both occur at a rate of about 1%. </li></ul>
  18. 18. Hypersensitivity reactions <ul><li>Given the risk of anaphylaxis, antivenin should be given only in a setting in which full resuscitative measures , including: </li></ul><ul><li>* Oxygen, </li></ul><ul><li>* Endotracheal intubation, </li></ul><ul><li>* Intravenous fluid administration, and </li></ul><ul><li>* Epinephrine, </li></ul><ul><li>are available . </li></ul>
  19. 19. Hypersensitivity reactions <ul><li>Patients should be asked about medication allergies and previous exposure to antivenins. </li></ul><ul><li>If equine-derived products are to be used, skin testing may be done, but the practice remains controversial. </li></ul>
  20. 20. Hypersensitivity reactions <ul><li>Skin testing </li></ul><ul><li>1. Delays treatment </li></ul><ul><li>2. Has triggered anaphylaxis and </li></ul><ul><li>serum sickness. </li></ul><ul><li>3. Has very high false-positive and </li></ul><ul><li>false-negative rates of up to 30%. </li></ul>
  21. 21. Hypersensitivity reactions <ul><li>The skin test is performed using 0.02 mL </li></ul><ul><li>of a 1:10 dilution of antivenin. </li></ul><ul><li>A positive skin test does not preclude the use of antivenin but does alert the clinician to an increased risk of anaphylaxis. </li></ul>
  22. 22. Envenomations <ul><li>In such instances, pretreatment with intravenous administration of Diphenhydramine , 1 mg/kg, and Methylprednisolone , 1–2 mg/kg, is required. </li></ul><ul><li>Some toxicologists recommend pretreatment for all patients receiving antivenin </li></ul>
  23. 23. Envenomations <ul><li>If signs of immediate hypersensitivity develop during administration of antivenin, the infusion should be stopped until the patient is stabilized. </li></ul>
  24. 24. Envenomations <ul><li>If the severity of envenomation warrants continued infusion of antivenin, it may be: </li></ul><ul><li>Resumed at a slower rate </li></ul><ul><li>or </li></ul><ul><li>Simultaneously with administration </li></ul><ul><li>of epinephrine. </li></ul>
  25. 25. Envenomations <ul><li>Delayed hypersensitivity or serum sickness develops: </li></ul><ul><li>- In up to 65% of patients who </li></ul><ul><li>receive equine-derived antivenin </li></ul><ul><li>and </li></ul><ul><li>- In 15% of patients who receive </li></ul><ul><li>ovine-derived products. </li></ul>
  26. 26. Envenomations <ul><li>Serum sickness usually develops 5–21 days </li></ul><ul><li>after exposure and may last for weeks. It is </li></ul><ul><li>most commonly manifested as </li></ul><ul><li>1.Urticaria </li></ul><ul><li>2.Pruritus </li></ul><ul><li>3.Arthralgia, and malaise, </li></ul><ul><li>rarely may present as </li></ul><ul><li>1. Immune complex glomerulonephritis </li></ul><ul><li>2. Neuritis or </li></ul><ul><li>3. Myocarditis </li></ul>
  27. 27. Envenomations <ul><li>Intradermal skin tests have not been shown to predict the risk of serum sickness accurately. </li></ul><ul><li>Prophylactic use of antihistamines and corticosteroids may reduce the risk of serum sickness and definitely is of benefit if symptoms develop. </li></ul>
  28. 28. SNAKEBITE <ul><li>Of the >3,000 known species of snakes, only 200 are poisonous to humans. Of poisonous snakes, 90% are members of one of three families : </li></ul><ul><li>1. the Hydrophidae , or poisonous sea snakes; </li></ul><ul><li>2.the Elapidae , which includes the cobras, </li></ul><ul><li>mambas, and coral snakes; and </li></ul><ul><li>3.the Viperidae , or true vipers </li></ul>
  29. 29. <ul><li>In the U.S., 95% of poisonous snakebites are inflicted by the Crotalidae, or pit vipers , which are a subfamily of the true vipers. Pit vipers may be identified by their: </li></ul><ul><li>* Triangular heads </li></ul><ul><li>* Elliptical eyes , and </li></ul><ul><li>* Identifiable pit between the eyes and </li></ul><ul><li>nose </li></ul>SNAKEBITE
  30. 30. SNAKEBITE <ul><li>Members of the pit viper family in the U.S. include: </li></ul><ul><li>1. rattlesnakes </li></ul><ul><li>2. cottonmouths , and </li></ul><ul><li>3. copperheads . </li></ul>
  31. 31. SNAKEBITE <ul><li>Coral snakes , the other poisonous snakes native to the U.S., are found in Texas and the Southeast and are members of the Elapidae family. </li></ul><ul><li>Coral snakes are small with : </li></ul><ul><li>* Small, rounded head and </li></ul><ul><li>* Brightly colored bands of black and red </li></ul><ul><li>separated by more narrow yellow bands . </li></ul>
  32. 32. SNAKEBITE <ul><li>The rhyme “ red on yellow , kill a fellow ; red on black , venom lack ” serves to differentiate the coral snake from the similar-appearing but nonpoisonous scarlet king snake. </li></ul>
  33. 33. SNAKEBITE <ul><li>Cobras and kraits </li></ul><ul><li>are common in parts of Asia </li></ul><ul><li>whereas vipers , cobras , and adders </li></ul><ul><li>are common in parts of Africa. </li></ul>
  34. 34. Epidemiology <ul><li>The incidence of snakebites is; </li></ul><ul><li>Higher in </li></ul><ul><li>- Africa </li></ul><ul><li>* 5 bites per1000 persons in Nigeria </li></ul><ul><li>* 23000 snake bites deaths per year </li></ul><ul><li>in West Africa </li></ul><ul><li>- Australia </li></ul><ul><li>0.6 to 5 bites per 1000 </li></ul><ul><li>- Asia </li></ul><ul><li>- South America </li></ul>
  35. 35. Epidemiology (cont.) <ul><li>In USA ,most snakebites occur in young males and involve alcohol intoxication; often the victim had tried to capture or play with snake. </li></ul><ul><li>In Africa and Asia most bites occur on lower limbs ,at night ,and provoked by stepping on a snake </li></ul>
  36. 36. Epidemiology (cont.) <ul><li>In USA </li></ul><ul><li>there are only 12 -15 deaths each year </li></ul><ul><li>In parts of Africa and Asia </li></ul><ul><li>where as case fatality rates up to 15% are reported among hospitalized victims of snakebites where intensive care and antivenom access are limited </li></ul>
  37. 37. Pathogenesis <ul><li>Snake venom is a mixture of; </li></ul><ul><li>-Polypeptides </li></ul><ul><li>-Proteolytic enzymes </li></ul><ul><li>-Toxins (species-specific) </li></ul>
  38. 38. Pathogenesis (cont.) <ul><li>Venom of the Elapidae and the Hydrophidae is primarily neurotoxic and has a curare- like effect by blocking neurotransmission at the neuromuscular junction </li></ul><ul><li>Death results from respiratory depression </li></ul>
  39. 39. Pathogenesis (cont.) <ul><li>Crotalidae venom is cytolytic ,causing </li></ul><ul><li>1. tissue necrosis </li></ul><ul><li>2. vascular leak </li></ul><ul><li>3.coagulopathies </li></ul><ul><li>Death from pit viper bites results from: </li></ul><ul><li>1. hemorrhagic shock </li></ul><ul><li>2.adult respiratory distress syndrome </li></ul><ul><li>3. renal failure </li></ul>
  40. 40. Clinical manifestations <ul><li>Pit viper bites </li></ul><ul><li>-occur usually on the extremities </li></ul><ul><li>- pain and swelling occur at the site </li></ul><ul><li>within minutes </li></ul><ul><li>- as the venom moves proximally , edema </li></ul><ul><li>and ecchymosis advance </li></ul><ul><li>- in severe cases , bulla formation and tissue </li></ul><ul><li>necrosis ensue </li></ul>
  41. 41. Clinical manifestations (cont.) <ul><li>Pit viper bites (cont.) </li></ul><ul><li>- systemic symptoms include ; </li></ul><ul><li>* nausea, vomiting </li></ul><ul><li>* diaphoresis </li></ul><ul><li>* weakness </li></ul><ul><li>* tingling around the face </li></ul><ul><li>* muscle fasciculation </li></ul><ul><li>Gold BS,Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  42. 42. Clinical manifestations (cont.) <ul><li>Pit viper bites (cont.) </li></ul><ul><li>* Rarely .may present with : </li></ul><ul><li># generalized edema </li></ul><ul><li># cardiac arrhythmias </li></ul><ul><li># complex clotting abnormalities </li></ul><ul><li>Gold BS,Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  43. 43. Clinical manifestations (cont.) <ul><li>The coral snakes bites </li></ul><ul><li>Bites of most Elapidae, including the coral snakes </li></ul><ul><li>are minimally painful because the venom has no cytotoxin </li></ul><ul><li>Lack of immediate symptoms should not be mistaken for the absence of serious envenomation </li></ul><ul><li>- </li></ul><ul><li>Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  44. 44. Clinical manifestations (cont.) <ul><li>The venom of the coral snake is primarily neurotoxic , and symptoms can progress rapidly in a few hours </li></ul><ul><li>from </li></ul><ul><li>mild drowsiness </li></ul><ul><li>to </li></ul><ul><li>cranial nerve palsies </li></ul><ul><li>weakness </li></ul><ul><li>and </li></ul><ul><li>death from respiratory failure </li></ul><ul><li>Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  45. 45. Treatment <ul><li>First: determine whether the bite was by a poisonous snake and if envenomation occurred </li></ul><ul><li>Immediate care is to immobilize the bitten extremity and transport the patient quickly to the nearest hospital If the bite is determined to be from a venomous snake </li></ul><ul><li>Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  46. 46. Treatment <ul><li>Avoid applying of ice to the bite site or using excision and suction as it is believed to cause more tissue damage than benefit </li></ul><ul><li>Many experts now eschew any constricting bands because of the risk of ischemia </li></ul><ul><li>Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  47. 47. Treatment <ul><li>On arrival at the emergency department </li></ul><ul><li>1. a large-bore i.v line should be inserted </li></ul><ul><li>2. initial blood tests should include; </li></ul><ul><li>i. type and cross match’ </li></ul><ul><li>ii. Complete blood cell and platelets counts </li></ul><ul><li>iii. Prothrombine and partial thromboplastin times </li></ul><ul><li>iv. Fibrinogen and fibrin degradation products’ </li></ul><ul><li>v. Blood urea nitrogen ,creatinine, and creatine phosphokinase level </li></ul><ul><li>these investigations must be repeated at intervals depending on severity of envenomation </li></ul><ul><li>Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  48. 48. Treatment <ul><li>baseline vital signs and measurement of circumference of the bitten extremity should be obtained and demarcation of 3eccyhmosis and swelling should be marked on the limb </li></ul><ul><li>The wound should be cleansed and tetanus toxoid given if appropriate </li></ul><ul><li>Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  49. 49. Treatment <ul><li>Usage of antivenin </li></ul><ul><li>It depends on the severity and progression of symptoms </li></ul><ul><li>Rattlesnake envenomation requires antivenin </li></ul><ul><li>Copperhead bites do not </li></ul><ul><li>Cottonmouth bites fall between these extremes </li></ul><ul><li>Gold BS, Dart RC, Barish RA: bites of venomous snakes, N Engl J Med 2002;347:347-356 </li></ul>
  50. 50. The severity of envenomation is commonly graded on a 4 –point scale Minimal envenomation (local swelling and pain without progression) Grade 1 No envenomation Grade 0 Features Grade
  51. 51. The severity of envenomation (Cont,) Severe envenomation (marked local response ,severe systemic findings and significant alteration in laboratory findings Grade 3 Moderate envenomation (swelling ,pain , or ecchymosis progress beyond the site of injury Mild systemic or laboratory manifestations) Grade 2 Features Grade
  52. 52. Antivenin <ul><li>Is most effective if delivered within 4 hr of the bite </li></ul><ul><li>Is of little value if administration is delayed beyond 12 hr </li></ul><ul><li>Poses a small ,but significant risk of an immediate hypersensitivity reaction </li></ul>
  53. 53. Antivenin <ul><li>Antivenin (Crotalidae) Polyvalent </li></ul><ul><li>- is administered in increments of 5 vials and repeated every 2hr as needed to neutralize circulating venom, as measured by; </li></ul><ul><li>- normalization of clotting parameters </li></ul><ul><li>- A halt in the progression of swelling of the affected limb </li></ul><ul><li>- children often require more antivenin than a similarly envenomated adult because of their small volume-to venom ratio </li></ul>
  54. 54. <ul><li>Thank you </li></ul>

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