INFECTIOUS DISEASES

Topic: Snake Bite

Lecturer: Dr. San Diego

SNAKE BITE
 Well-known occupational hazard
o Farmers
o Plantation workers
o Other outdoor workers
 Results in much morbidity and mortality throughout the world
 This occupational hazard is no more an issue restricted to a particular
part of the world
 It has become a global issue
 Accounts 30,000-40,000 deaths annually
 It is certain to be higher than what is reported
o Because even today, most of the victims initially approach
traditional healers for treatment and many are not even
registered in the hospital
 Philippines – there are no reliable estimates of mortality among the
many islands of the archipelago
Picture Above: Identification Features of Poisonous vs Non-poisonous Snakes
 Figures of 200-300 deaths each year have been suggested
 Only Cobras cause fatal envenoming, their usual victims being Rice Poisonous (Venomous) snakes – their head are usually triangular; their eyes
Farmers (pupil) are elliptical; It HAS fangs
Non-poisonous (Nonvenomous) snakes – their head are usually rounded;
These cobras are usually found on the Northern part of Luzon or
their eyes (pupil) are rounded; It does NOT have any fangs
Central Luzon where rice farming is common

VENOM
 Not all snakes are fatal
Composition:
o Majority of snakes are not poisonous
 More than 90% of snake venom is protein
List of Poisonous Snakes:  Each venom contains more than a hundred different proteins
 Cobra A. Enzymes
 Copperhead B. Non-enzymatic polypeptide toxins
 Coral snake – usually found in South Philippines (Palawan; Mindanao) C. Non-toxic proteins such as nerve growth factor
 Cottonmouth (water moccasin)
 Rattlesnake Venom Enzymes:
 Various snakes found in zoos  Zinc Metalloproteinase (Hemorrhagins):
o Damage vascular endothelium, causing bleeding
Classification of Poisonous Snake:
This enzyme damages the endothelium (arteries, veins)
 There are 2 important groups (families) that causes spontaneous bleeding which is a common
o Elapidae manifestation of snake bites
 Have short permanent erect fangs
 This family includes the cobras, kraits, coral snakes,  Procoagulant Enzymes:
and the sea snakes o These enzymes stimulate blood clotting with formation of
o Viperidae fibrin in the blood stream
 Have long fangs which are normally folded up against Since this enzymes stimulate blood clotting, there
the upper jaw but, when the snake strikes, are erected shouldn’t be any bleeding right? But the problem here is
 King Cobras and Vipers that it overconsumes the fibrin  leads to a very low fibrin
count therefore enhances the bleeding

 Phospholipase A2 (Lecithinase):
o Damages mitochondria, red blood cells, leucocytes, platelets,
peripheral nerve endings, skeletal muscle, vascular
endothelium
Important thing why snakes wants to increase its venom to
its prey is to paralyze its prey (through damaging the
abovementioned cells)

o Produces:
 Presynaptic neurotoxic activity – causes paralysis
 Opiate-like sedative effects
This contributes to the weakness, paralysis or
prostration
Prostration – the victim feels that they are totally
Picture Above: Poisonous vs. Non-Poisonous Snake Bite exhausted to the point that they cannot move
Poisonous snakes – have fang marks; it is like a bite of a “vampire” where
there are 2 punctured wounds in close proximity (distance usually 1 and a  Leads to release of histamine and anti-coagulation
half inch apart) ↑ histamine causes hypotension/↓ BP  one
Non-poisonous snakes – have multiple punctured wounds; Common bites reason why we immediately need to give
usually come from Pythons antihistamine because if not = SHOCK

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 INFECTIOUS DISEASES
Topic: Snake Bite
Lecturer: Dr. San Diego

Venom Enzymes continued….. EARLY SYMPTOMS AND SIGNS

 Acetylcholinesterase  Increasing local pain (burning, bursting, throbbing) at the site of the
o Found in most elapid venoms bite
o It does not contribute to their neurotoxicity  Local swelling that gradually extends proximally up to the bitten limb
and tender
 Hyaluronidase  Painful enlargement of the regional lymph nodes draining the site of
o Promotes the spread of the venom through tissues the bite

 Other Proteolytic Enzymes (Metalloproteinases, Endopeptidases,

Bites by Kraits, Sea Snakes and Philippine Cobras may be virtually painless
Hydrolases) / Polypeptide Cytotoxins (also known as Cardiotoxins) and may cause negligible local swelling
o Increase vascular permeability causing edema, blistering,
bruising and necrosis at the site of the bite
Further increase vascular permeability  which is why LOCAL SYMPTOMS AND SIGNS
another manifestation of snake bites are edema, blistering,  Fang marks
bruising and leading to the point of necrosis  Local bleeding
 Bruising
CATEGORY OF SNAKES (WHO)  Blistering
Categorization of snakes by WHO is more focused on the epidemiology (unlike  Lymph node enlargement
in rabies, categories is based on the classification of bites)  Inflammation
 Blistering
Category 1: Highest medical Importance  Local infection
 Highly venomous snakes which are common or widespread and cause  Necrosis
numerous snake-bites, resulting in high levels of morbidity, disability or Necrosis usually happens if first aid was done wrongly  leads to
mortality amputation
 Here in the Philippines, we are in Category 1 because the only species of
snake that causes common bites and snake bites resulting to mortality GENERALIZED (SYSTEMIC) SYMPTOMS AND SIGNS
and morbidity are the Philippine Cobras  Nausea
 Categorization is important in terms of securing or procuring your anti-  Vomiting
venom  Malaise
 Category 1  we only use the monovalent anti-venom  Abdominal pain
 Weakness
Category 2: Secondary medical importance  Drowsiness
 Highly venomous snakes capable of causing morbidity, disability, or  Prostration
death, but: Prostration  feeling of being totally exhausted that they usually
a) For which exact epidemiological or clinical data are lacking or want to lay in bed. They may look like sleeping but they are actually
b) Are less frequently implicated because of their behavior, awake. They usually answer only in phrases with their eyes closed
habitat preferences or occurrence in areas remote to large
human population CARDIOVASCULAR (VIPERIDAE)
 Countries included are Thailand, India and Indonesia  Visual disturbances
 Category 2  since they have several snakes that causes envenoming,  Dizziness
they use the polyvalent anti-venom  Faintness
 Collapse
HOW DO SNAKE BITES HAPPEN?  Shock/Hypotension
 Snake bite is an occupational hazard of rice farmers  Cardiac Arrhythmias
 Most snake bites happen when the snake is trodden on (stepped on) o Commonly are Bradycardia
 The snake may be picked up:  Pulmonary Edema
o Unintentionally in a handful of foliage  Conjunctival Edema (Chemosis)
o or Intentionally by someone who is trying to show off
 Some bites occur at home during the night in search of its prey BLEEDING AND CLOTTING DISORDERS
Traumatic and Spontaneous Systemic
Picture On Left:  Intracranial hemorrhage
Snake Whisperer (Abu Zarin Hussin)  Epistaxis
 Hemoptysis
The 33-year-old Malaysian firefighter  Hematemesis
who had earned the name the “snake  Melena
whisperer” died Friday, a few days  Hematuria
after he was bitten by a cobra. Hussin  Vaginal bleeding
was rushed to a hospital Monday  Skin (Petechiae, Purpura, Ecchymoses)
after he was bitten in Bentong in the
state of Pahang, the Malaysian news
outlet the Star Online reported

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 INFECTIOUS DISEASES
Topic: Snake Bite
Lecturer: Dr. San Diego

NEUROLOGICAL MANIFESTATIONS MANAGEMENT

 Drowsiness  The first aid being currently recommended is based around the
 Paresthesia mnemonic:
 Abnormalities of taste and smell “Do it R.I.G.H.T.”
 Ptosis  R = Reassure the patient. 70% of all snakebites are from non-venomous
 External ophthalmoplegia species. Only 50% of bites by venomous species actually envenomate
 Paralysis of facial muscles and other muscles innervated by the cranial the patient
nerves  I = Immobilise in the same way as a fractured limb. Use bandages or
 Aphonia cloth to hold the splints, not to block the blood supply or apply pressure.
 Difficulty in swallowing Do not apply any compression in the form of tight ligatures, they can be
 Respiratory and generalized flaccid paralysis dangerous!
 G. H. = Get to Hospital Immediately. Traditional remedies have NO
Lecture Discussion: PROVEN benefit in treating snakebite.
What we have to remember here is that what is evident in neurological  T = Tell the doctor of any systemic symptoms such as ptosis that
manifestations are ABNORMALITIES OF THE CRANIAL NERVES manifest on the way to hospital.

SKELETAL MUSCLE FIRST AID TREATMENT

 Generalized pain
 Stiffness
 Tenderness of muscles
 Trismus
 Myoglobinuria
 Hyperkalemia
 Cardiac Arrest
 Acute Renal Failure
 Lower back pain
 Hematuria
 Hemoglobinuria
 Myoglobinuria
 Oliguria/Anuria
 Symptoms of Signs and Uremia
 Aims of first-aid attempt to retard systemic absorption of venom
 Preserve life and prevent complications before the patient can receive
Very common in patients who are medical care
bitten by Kraits or Sea Snakes
 Control distressing or dangerous early symptoms of envenoming
 Arrange the transport of the patient to a place where they can receive
medical care
 ABOVE ALL, AIM TO DO NO HARM!
 Reassure the victim who may be very anxious
RENAL  Immobilize the patient’s body by laying down in a comfortable and safe
position
 Immobilize the bitten limb with a splint or sling
o Any movement or muscular contraction increases absorption of
venom into the blood stream and lymphatics
 Avoid any interference with the bite wound such as:
o Incisions, rubbing, vigorous cleaning, massage, application of
herbs or chemicals
 As this may introduce infection, increase absorption of
venom and increase local bleeding
Snake bites are unlike rabies bites wherein we
need to clean the bite wound. It is recommended
that we do not do any interference at the site of
the snake bite

 Tight (arterial) tourniquets are NOT RECOMMENDED (level of

evidence E):
o Traditional tight (arterial) tourniquets are not recommended.
To be effective, these had to be applied around the upper part
of the limb so tightly that the peripheral pulse gets occluded.
This method can be extremely painful and very dangerous if
the tourniquet was left on for too long (more than above 40
minutes), as the limb might be damaged by ischemia.
Tourniquets have caused many gangrenous limbs
**This was skipped during the Lecture**
Transport to Hospital
 Treatment in the Hospital
o Rapid primary clinical assessment and resuscitation: ABCDE
approach
 Airway
 Breathing (respiratory movements)
 Circulation
 Disability of the nervous system (level of
consciousness)
 Exposure and environmental control (protect from
cold, risk of drowning etc.)

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 INFECTIOUS DISEASES
Topic: Snake Bite
Lecturer: Dr. San Diego

Lecture Discussion: ABCDE Approach LABORATORY TESTS

How do we know if the patient is breathing? We can know if the person is
breathing on his own by looking at the rise and fall of chest
Consciousness of the patient can be assessed using the Glasgow Coma Scale
Treatment in the Hospital continued…..
 Clinical Situations requiring Urgent Resuscitation:
o Profound hypotension
 Release of inflammatory vasoactive mediators
 Anaphylaxis induced by the venom itself
o Terminal Respiratory Failure
 Paralysis of the respiratory muscles
 There will be a need to intubate the patient
o Cardiac Arrest
 Precipitated by hyperkalemia
 If patient is pulseless = do rescue maneuvers
(ACLS/BLS)
 Giving of vasopressors (epinephrine)
o Vasculotoxic patients
 Bleeding from multiple orifices with hypotension,
reduced urine output, obtunded mentation (drowsy,
confused), cold extremities
1. Need urgent attention
2. ICU care
3. Volume replacement
4. Pressor support
5. Dialysis
6. Infusion of blood and blood products
 20-minute whole blood clotting test (20WBCT)
o Place 2 ml of freshly sampled venous blood in a small, new
or heat cleaned, dry, glass vessel
o Leave undisturbed for 20 minutes at ambient
temperature
o Tip the vessel once
o If the blood is still liquid (unclotted) and runs out, the
patient has hypofibrinogenaemia (incoagulable blood) as
a result of venom induced consumption coagulopathy
o In the South-East Asia region, incoagulable blood is
diagnostic of a viper bite and rules out an elapid bite
o Warning! If the vessel used for the test is not made of
ordinary glass, or if it has been cleaned with detergent,
its wall may not stimulate clotting ofthe blood sample
(surface activation of factor XI – Hageman factor) and
test will be invalid
o If there is any doubt, repeat the test in duplicate, including
a “control” (blood from a healthy person)
 Hemoglobin concentration/Hematocrit
 Platelet count
 White blood cell count
 Blood film
 Plasma/Serum
 Biochemical abnormalities:
o Aminotransferases and muscle enzymes
 Arterial blood gases and pH
 Urine examination
WHAT IS ANTIVENOM?

o Neuroparalytic patients
 Respiratory paralysis, tachypnea or bradypnea or
paradoxical respiration, obtunded mentation, and
peripheral skeletal muscle paralysis
1. Need urgent ventilator management
2. Endotracheal intubation
3. Ventilation bag or Ventilator assistance

DETAILED CLINICAL ASSESSMENT AND SPECIES DIAGNOSIS

 A precise history of circumstances of the bite and the progression of
local and systemic symptoms and signs is very important
o “IN WHAT PART OF THE BODY HAVE YOU BEEN BITTEN?”
o “WHEN AND UNDER WHAT CIRCUMSTANCES WERE YOU
BITTEN?”
o “Where is the snake that bit you?”
o “How are you feeling now?”

 Physical examination: General examination

o Measure the blood pressure and heart rate
o Examine the skin and mucous membranes
o The conjunctivae
o Thoroughly examine the gingival sulci
o Abdominal tenderness
o Loin (low back) pain Lecture Discussion: Antivenom
o Intracranial hemorrhage From the picture itself, we can see that initially it is coming from a horse (an
o Convulsions or impaired consciousness animal that is already immunized to the venom toxoid). Initially we get a
venom from the snake and then introduced to an animal and then later blood
will be taken from the animal to be purified for us to get the antibody,
concentrate it  we now get a Purified Cobra Antivenom (PCAV)

RITM is the only cobra snake antivenom producer and distributor in the
Philippines

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 INFECTIOUS DISEASES
Topic: Snake Bite
Lecturer: Dr. San Diego
Antivenom Treatment:
 First introduced by Albert Calmette at the Institut Pasteur in Saigon
1890s
 Immunoglobulin purified from the plasma of:
o Horse
o Mule
o Donkey (Equine)
o Sheep (Ovine)
that has been immunized with the venoms of one or more species of
snakes
“Specific” Antivenom:
 Contain specific antibody that will neutralize that particular venom and
perhaps the venoms of closely related species (Paraspecific
Neutralization)
1. Monovalent (Monospecific) Antivenom
o Neutralizes the venom of only one species of snake
2. Polyvalent (Polyspecific) Antivenom
o Neutralizes the venom of several different species of snakes,
usually the most important species, from a medical point of
view, in a particular geographical area
Indications for Antivenom Treatment:
 Antivenom should be given only to patients in whom benefits are
considered likely to exceed its risks. Since antivenom is relatively costly
and often in limited supply, it should not be used indiscriminately. The
risk of reactions should always be taken into consideration (level of
evidence E)
 Antivenom treatment is recommended if and when a patient with
proven or suspected snake-bite develops one or more of the following
signs:
o Systemic Envenoming
 Haemostatic abnormalities: spontaneous systemic
bleeding (clinical), coagulopathy (20WBCT or other
laboratory such as prothrombin time) or
thrombocytopenia (<100 x 109/liter) (laboratory)
 Neurotoxic signs: ptosis, external ophthalmoplegia,
paralysis etc (clinical)
 Cardiovascular abnormalities: hypotension, shock,
cardiac arrhythmia (clinical), abnormal ECG
 Acute renal failure: oliguria/anuria (clinical), rising
blood creatinine/ urea (laboratory)
 (Hemoglobin-/myoglobin-uria:) dark brown urine
(clinical), urine dipsticks, other evidence of
intravascular hemolysis or generalized
rhabdomyolysis (muscle aches and pains,
hyperkaliemia) (clinical, laboratory)
 Supporting laboratory evidence of systemic
envenoming
o Local Envenoming
 Local swelling involving more than half of the bitten
limb (in the absence of a tourniquet)
 Swelling after bites on the digits (toes and especially
fingers)
 Rapid extension of swelling (for example beyond the
wrist or ankle within a few hours of bites on the hands
or feet)
 Development of an enlarged tender lymph node
draining the bitten limb
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Administration of Antivenom:
 Freeze-dried (lyophilised) antivenoms are reconstituted, usually with 10
ml of sterile water for injection per ampoule
 Two methods of administration are recommended:
1. Intravenous “push” injection:
o Reconstituted freeze-dried antivenom or neat liquid
antivenom is given by slow intravenous injection (not
more than 2 ml/minute)
o This method has the advantage that the
doctor/nurse/dispenser giving the antivenom must
remain with the patient during the time when some
early reactions may develop. It is also economical,
saving the use of intravenous fluids, giving sets,
cannulae etc.
2. Intravenous infusion:
o Reconstituted freeze-dried or neat liquid antivenom is
diluted in approximately 5-10 ml of isotonic fluid per
kg body weight
o Example: 250-500 ml of isotonic saline or 5% dextrose
in the case of an adult patient) and is infused at a
constant rate over a period of about one hour.
Patient must be closely observed for at least 1 hour after starting
intravenous antivenom administration, so that early anaphylactic antivenom
reactions can be detected and treated early with epinephrine (adrenaline)
HOW LONG AFTER THE BITE CAN ANTIVENOM BE EXPECTED TO BE
EFFECTIVE?
 It may reverse systemic envenoming even when this has persisted for
several days or, in the case of haemostatic abnormalities, for two or
more weeks.
CAN WE DO LOCAL ADMINISTRATION OF THE ANTIVENOM?
 Local administration of antivenom at the site of the bite is not
recommended:
o It should not be used as it is extremely painful
o May increase intracompartmental pressure
o Not been shown to be effective
 Intramuscular injection of antivenom:
o Antivenoms are large molecules
o Are absorbed slowly via lymphatics
o Bioavailability is poor
o Pain of injection of large volumes of antivenom
DOSE OF ANTIVENOM
 No image available
 Basically, the table shown during the lecture only gives us an idea that
if the country is Category 2  there will be different manufacturers of
the antivenom. Category 1 (like the Philippines)  RITM is the sole
producer and distributor of antivenom
Picture on Left:
This is a study that shows that the
Philippines should also buy the
polyvalent antivenom because
there is another species of
venomous snake that is increasing
(it is the Samar Cobra). Since there
is no polyvalent antivenom
available here, there is a need to
double the dose of monovalent
antivenom = too expensive for
patients bitten by the Samar Cobra
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 INFECTIOUS DISEASES
Topic: Snake Bite
Lecturer: Dr. San Diego

RESPONSE TO ANTIVENOM  Dark Brown Urine (Myoglobinuria or Hemoglobinuria):

General Patients: o Correct hypovolemia with intravenous fluid
 The patient feels better o Correct acidosis with a slow IV infusion of 5-100 mmoL of
o Nausea, headache and generalized aches and pains may sodium
disappear very quickly o Consider a single infusion of mannitol- 200 mL of 20% mannitol
 Spontaneous systemic bleeding (e.g. from the gums): may be infused IV over 20 minutes
o This usually stops within 15-30 minutes
 Blood coagulability (as measured by 20WBCT)
o This is usually restored in 3-9 hours
 Bleeding from new and partly healed wounds
o Stops much sooner than this

In Shocked Patients:
 Blood pressure may increase
o Within the first 30-60 minutes
o Arrhythmias and sinus bradycardia may resolve
 Neurotoxic envenoming of the post-synaptic type (Cobra bites)
o Begin to improve as early as 30 minutes after antivenom, but
usually takes several hours
 Active hemolysis and rhabdomyolysis
o Cease within a few hours and the urine return to its normal  Severe Local Envenoming: Local Necrosis/Intracompartmental
color Syndromes
o Surgical intervention may be needed
ANTIVENOM REACTION o Prophylactic broad spectrum antimicrobial treatment is
 Epinephrine (Adrenaline) should always be drawn up in readiness justified
before antivenom is administered

At the earliest sign of a reaction:

 Antivenom administration must be temporarily suspended
 Epinephrine (adrenaline) (0.1% solution, 1 in 1,000, 1 mg/mL) is the
effective treatment for early anaphylactic and pyrogenic antivenom
reactions

WHAT IF?
 What if there is no antivenom? What will you do?
o What we should do is conservative management (alleviate
the patient’s symptoms)

Conservative Treatment when No Antivenom is Available

 Neurotoxic envenoming with respiratory paralysis
o Assisted ventilation. This has proved effective, and has been
followed by complete recovery, even after being maintained
for periods of more than one month.
o Manual ventilation (anesthetic bag) by relays of doctors,
medical students, relatives and nurses has been effective
where no mechanical ventilator was available.
o Anticholinesterases should always be tried

 Hemostatic Abnormalities
o Strict bed rest to avoid even minor trauma
o Transfusion of clotting factors and platelets
o Ideally, fresh frozen plasma and cryoprecipitate with platelet
concentrates
 If these are not available, fresh whole blood
o Intramuscular injections should be avoided

 Shock/Myocardial Damage
o Hypovolemia should be corrected with colloid/ crystalloids
o Controlled by observation of the central venous pressure
o Ancillary pressor drugs (dopamine or epinephrine-adrenaline)
may also be needed
o Patients with hypotension associated with bradycardia should
be treated with atropine

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