Morning Report - 1October 28, 2016

Khushboo Gandhi, PGY2Internal Medicine, St. Luke’s Hospital

CC: 52 Year Old Caucasian Male Presents With A Snakebite

HPI:Doing some fertilization in his yard around 1:30 pm, wearing sandals.

Never saw snake bit him; but felt sharp sting on his left toe; thought wasp bite.

Examined further; noticed 2 marks looking like snakebite.

Had noted some snakes in his backyard before.

15 minutes - ED

Observed for 5 hours in ED - Home - 4 hours later- Comes back with increasing swelling, pain and nausea.

ROS:Edema of left lower legJoint pain - Left ankleNauseaAbdominal pain

PMH/PSH: Allergic Rhinitis, Left knee arthroscopic surgery

Allergies: NKDA

Family History: Father - CAD

Social History: Married; Lives with wife in Glencoe, MO Drinks 2-3 glasses of beer/wine every dayNever smokerNever drug user

Meds: Flonase, Claritin, Afrin, Tylenol, Multivitamin

Physical examination:Vitals: TMax: 37.5; HR: 87 regular; RR: 16; SpO2: 99 on RA; BP: 186/100 mm hg.Height: 172 cm Weight: 80.1 kg

General: alert and oriented, no acute distress

Skin: Warm, dry, pink. 2 small puncture marks at the base of the left great toe anteriorly measuring approximately 1 cm apart. Musculoskeletal: The base of the left great toe has 2 puncture wounds. The left foot is swollen with significant edema up to the ankle but not above, no ecchymosis, no tenderness. Distal half of the foot and heel area are colder than the rest of the foot, No other signs of injury.

After 6 hours…Swelling and ecchymosis extending to toes and lower leg, no blistering.

HEENT: normocephalic, moist oral mucosa, no pharyngeal erythema

Neck: non tender, supple, no carotid bruit, no JVD, no lymphadenopathy, no thyromegaly

Cardiovascular: Normal rate, regular rhythm, no murmur or gallops, pulses in all extremities

Pulmonary: Lungs CTA, non labored respirations, BS equal, symmetrical expansion, no chest wall tenderness

GI: Soft, nontender, nondistended, normal bowel sounds, no organomegaly

Neuro: Alert, oriented, normal sensory, normal motor, no focal defects, CN II-XII intact, normal DTRs, Normal speech and coordination

Psychiatric: Cooperative. appropriate mood & affect. normal judgment.

What are you worried about?Venomous/Nonvenomous

Local tissue necrosis

Rhabdomyolysis

Coagulopathy/Hemorrhage

Hypotension/Shock

Neurotoxins - Paralysis

CBC

 WBC 11.7RBC 4.13Hemoglobin 13.9Hematocrit 39.7MCV 96.1MCH 33.7MCHC 35.0RDW 13.0Platelets 261MPV 9.9

DiffNeutro % 83Lymph % 8Mono % 7Eos % 1Baso % 0Immature Gran %

0.3

Neutro # 9.8Lymph # 1.0Mono # 0.8Eos # 0.1Baso # 0.0

UAColor Colorles

sClarity ClearSpecific Gravity

1.006

pH 5.5LE Negativ

eNitrite Negativ

eProtein Negativ

eGlucose Negativ

eKetones Negativ

eUrobilinogen Negativ

eBilirubin Negativ

eBlood Negative

Other Labs:PT 14.5 14.4 14.0INR 1.1 1.1 1.0PTT 30.8 27.7 27.3Fibrinogen 214 227

FDP <10 <10 <10CK Total 274 402 260Myoglobin 99 Range <=121

Labs:

Hospital Course:CroFab 5 vials overnight - Repeated with 2 vials in morning.

Pt noted significant improvement in his pain, swelling and joint mobility.

Objective measurements and margins of left foot indicated decreased edema.

Good capillary refill and good flexion/extension of L. foot, ankle, and digits.

No evidence of hypotension, angioedema, or neurotoxicity.

CPK trending down. Repeat Hgb stable. Coags and fibrinogen WNL.

Discussed with poison control - Recommended no further treatment with antivenom.

Observed for ~24hrs in ICU after initial control of his progression - Discharged home.

SNAKEBITESEPIDEMIOLOGY:

1.8 to 2.5 million venomous snakebites occur worldwide each year

100,000 to 125,000 annual deaths

Most common in developing countries with poorly developed health reporting systems and many deaths occur before medical care can be provided

Southeast and South Asia (eg, India, Pakistan, Sri Lanka, and Bangladesh), sub Saharan Africa, and Latin America

Approximately 8000 bites annually from poisonous snake species in the United States, with 10 to 12 deaths annually

1. Rattlesnake – native to all states except Alaska, Hawaii, and Maine.

2. Water moccasin or cottonmouth – Southeast and South, from Virginia to Texas.

3. Copperhead – Eastern Half of the continental United States, from Massachusetts to Texas.

VENOM PROPERTIES

Wide variations in composition, potency, and sites of action

Locally acting toxins: Enzymes which cause tissue destruction through diverse mech.

Systemically acting toxins:

Neurotoxins (Presynaptic and Postsynaptic)

Myotoxins

Systemic hemostasis toxins

Cardiotoxins

FIRST AID:Reducing the spread of venom and Expediting transfer to an appropriate medical center.

Remove the patient from the snake's territory. Keep the patient calm and at rest, remaining as still as possible.Attempt to identify the snake only if it is safe for the patient and the rescuer, and it will not delay

transport of the patient to definitive medical care. Snake parts should not be handled directly. The bite reflex may remain intact in recently killed

snakes and permit further biting. A digital photo taken at a safe distance may be useful.Immobilize the injured body part in a functional position.Remove any rings, watches, or constrictive clothing from the affected extremity.Do not apply pressure immobilization, tourniquets, or constrictive dressings.Gently cleanse the wound. Withhold alcohol and drugs that may confound clinical assessment.Avoid potentially harmful therapies (Incision and oral suction, Mechanical suction devices,

Cryotherapy, Surgery, Electric shock therapy, Tourniquets)Transport the patient in the supine position to the nearest medical facility as quickly as possible.Do not allow the victim to walk because exertion and local muscle contraction may increase

snake venom absorption.

History:Where and when the bite occurred

A description of the snake

How the bite occurred and whether there was more than one bite

Any signs or symptoms and the timing of onset

Initial treatment and first aid that was provided, including timing of first aid

Any recent ethanol or recreational drug use that may modify the patient’s presentation

Pertinent past medical history, such as current medications (especially anticoagulants or beta blockers), any prior snakebites for which antivenom was given, or allergy to animals used in antivenom production (eg, horses, sheep, rabbits)

Clinical Features:Local effects

Presence of fang marks Redness, swelling, blistering, ecchymosispersistent blood ooze, or tissue necrosis

Degree of swelling Circumferential measurement at the point of greatest swelling Demarcation of the extent of swelling from the bite site for reference during repeated examinations

Swelling or tenderness of regional lymph nodes - venom spread

Systemic toxicity: Non specific systemic effectsNausea, vomiting, diarrhea, weakness, light headedness, diaphoresis, or chills

Cardiovascular Tachycardia, Hypotension, poor tissue perfusion,

Venom-induced vasodilationDirect myocardial depressionHypovolemia from bleeding or “third spacing” of fluids into the bitten limb

Tissue and muscle toxicity Rhabdomyolysis Compartment syndrome

Tests:Rapid urine dipstick positive for blood with microscopic urinalysis showing no RBCPositive urine for myoglobinIncreased serum creatine kinase, potassium, creatinine, and/or blood urea nitrogen EKG changes indicating hyperkalemia

Neurotoxicity - Common findings

PtosisOphthalmoplegia (partial or complete)Pupillary dilation (often unresponsive to light)Difficulty with swallowing or speakingPoor facial toneLimited mouth opening or tongue extrusionDroolingLimb weakness or flaccid paralysisGait disturbanceDecreased or absent reflexes

Generalized muscle weakness or Respiratory failure - delayed by few hours.

Effects on Cranial nervesObserved first

Presynaptic: Damage the terminal axon at the NMJ, through entry into the cellNot reversible with antivenom or anticholinesteraseTakes days to weeks for recovery

Postsynaptic:Target the acetylcholine receptor on the muscle endplate, blocking response to acetylcholine,

external to the cellFully reversed with antivenom, or anticholinesterases

Tests:1. Positive Tensilon (edrophonium) test indicates paralysis responsive to antivenom and

anticholinesterase2. Low maximal inspiratory and expiratory forces

CoagulopathyProcoagulant, Anticoagulant, Direct fibrinolytic, and Anti or Pro platelet activation

EpistaxisGingival oozingBleeding from venipuncture siteEcchymosis and bruisingClinically evident bleeding (hemoptysis, hematemesis, hematuria, intracranial hemorrhage)

Findings on Labs:ThrombocytopeniaAnemiaProlonged INR or aPTTDecreased fibrinogen Increased fibrin degradation products or D dimerWhole blood clotting test (resource limited settings)

Failure of the blood to clot in a clean glass tube after 20 minutes - evidence of severe hypofibrinogenemia

Low sensitivity and high specificity.

Labs:Complete blood countSerum electrolytes and creatinine and blood urea nitrogenSerum creatine kinase (CK)Prothrombin time (PT) and partial thromboplastin time (PTT)International normalized ratio (INR)D dimer or fibrin degradation products (fibrin split products [FSP]) FibrinogenUrinalysis with microscopyUrine myoglobinElectrocardiogram

These studies should be repeated at regular intervals depending on pt’s clinical status.

Management:Antivenom administration is the mainstay for treatment

Supportive care: ABC

Airway managementRespiratory failure - rapid securing of the airway and support of breathingOxygen and bag mask ventilation followed by prompt rapid sequence intubationAtropine

BreathingEnd tidal carbon dioxide measurement and frequent assessment of maximal inspiratory and expiratory forces should be performed to detect evidence of impending respiratory failure.

CirculationShock - Intravenous isotonic fluids (eg, normal saline) and vasoactive infusions to maintain perfusion pressure depending upon whether shock is hypovolemic, cardiogenic, or both

NeurotoxicityAnticholinesterase (neostigmine) - Postsynaptic toxins

RhabdomyolysisIntravenous normal saline in volumes sufficient to establish urinary outputHemodialysis, as needed, for acute kidney injury

CoagulopathyBlood products (eg, whole blood, fresh frozen plasma, or platelets) only if life threatening bleeding and, after antivenom administrationHeparin, aminocaproic acid not helpful

ANTIVENOMMonovalent - Raised against a single genus or species of snake and are only effective for bites by that snake or group of snakes

Polyvalent - Developed against venoms from multiple different snakes that typically share a geographical region and can be used to treat envenomations by any of the included species

Fab antivenom — Polyvalent Crotalinae ovine immune Fab (FabAV, Crofab, Protherics) is the antivenom commercially available in the United States for Crotalinae (rattlesnake, water moccasin, or copperhead) envenomation.

Mechanism of action:FabAV consists of the purified Fab fragments of sheep immunoglobulin (IgG) raised against the antivenom of four snakes: Crotalus atrox (Western diamondback rattlesnake), Crotalus adamanteus (Eastern diamondback rattlesnake), Crotalus scutulatus (Mojave rattlesnake), Agkistrodon piscivorus (cottonmouth or water moccasin)

Fab fragments bind venom in the intravascular space and are renally excreted.

The half-life of FabAV is shorter than Crotalinae venom substances - recurrent toxicity is possible despite initial control of local and systemic effects - may necessitate repeated FabAV administration.

Most effective when given within six hours of envenomation.

Confused whether to administer antivenom?Seek expert consultation with a clinical toxicologist, poison control center (1-800-222-1222), or physician experienced in management of snakebites in the region.

Presenting with Life Threatening envenomation - Should receive antivenomCollapse, convulsions, weakness, paralysis, respiratory failure, shock, or bleeding

RhabdomyolysisAntivenom may attenuate but does not reverse rhabdomyolysis after a snakebite.

Local effects onlyWeigh the benefits and risks of giving antivenom to treat purely local effects

Potential candidates -

Rapid development of obviously severe local effects (such as blistering, bruising, hemorrhagic blebs, necrosis), or rapid progression of effects (eg, over one to two hours) to involve a substantial part of the bitten limb.

Evidence of systemic envenomation although findings may be nonspecific (eg, nausea, vomiting, or headache).

Facts:A listing of available antivenoms by region is available through the World Health Organization website (WHO snake and antivenom database) and at www.toxinology.com.

Prior to the availability of antivenoms active against Crotalinae snake bites and the widespread availability of emergency departments and critical care units, snakebite mortality ranged from 5 to 36 percent in the United States

After the introduction of Antivenin Crotalidae Polyvalent (ACP, Wyeth) in the 1950s and the development of widespread availability of emergency and critical care medicine starting in the 1960s, deaths from snake bite dropped to less than 1 percent.

AdministrationDosing - Snake species and individual patient characteristics.

Does not differ between adults and children; there is no "pediatric dose" for antivenom.

IV is preferred over IM

The patient should be monitored carefully for signs of adverse reactions during and for one hour following antivenom administration, regardless of route.

Resuscitation equipment and medications to treat anaphylaxis, most importantly, epinephrine (drawn up in a syringe or prepared for continuous IV infusion) should be immediately available.

Premedication with epinephrine is suggested when the administered antivenom is known to be associated with high rates of anaphylaxis.

Response to treatment

The typical timing to reversal of toxic effects

Coagulopathy – Spontaneous bleeding ceases by about 20 minutes. Coagulation tests often normalize by about 6 hours.It may take >24 hours to return to normal values in some cases.

Hypotension and cardiotoxicity – Marked improvement should occur within 20 to 30 minutes.

Neurotoxicity – responsive patients - Detectable improvement within 30 minutes with complete reversal within several hours

Failure to respondInsufficient antivenomWrong antivenomInactive or poor quality antivenomExcessive delay in administration after envenomationA venom effect not reversible by antivenom

Allergic reactions

3 typesEarly allergic reactionsPyrogenic reactionsLate allergic reactions (serum sickness)

Varies with different antivenom preparations, method of purification, the total foreign protein load and the composition of the antivenom (whole immunoglobulin compared with Fab fragments)

Rate of anaphylaxisUp to 80% for some antivenoms raised against Indian snakesCroFab, ViperaTAb, or Australian CSL/Seqirus antivenoms - < 5%

Resuscitation equipment and medications to treat anaphylaxis, most importantly, epinephrine (drawn up in a syringe or prepared for continuous IV infusion) should be immediately available.

Contraindications

Known allergy to FabAV, papaya, or papain comprise absolute contraindications to FabAV administration in patients with minimal toxicity after a Crotalinae snake (rattlesnake, water moccasin [cottonmouth], or copperhead) bite

Use with cautionPrior allergic reaction to antivenom or one of its componentsPatients with asthmaPatients receiving beta blockers or ACE inhibitors

Snakebites are considered tetanus prone wounds and prophylaxis should be provided as needed.

In patients with coagulopathy, tetanus prophylaxis should be postponed until after antivenom therapy and normalization of abnormalities.

In September 1957, someone from the Lincoln Park Zoo brought a young 30-inch snake to the Chicago Natural History Museum, to help identifying the snake

On September 25, 1957Schmidt found that snake was similar to the African boomslang snake, commonly found in sub Saharan Africa. While he was examining, snake suddenly bit him on his left thumb, leaving two 3 mm deep bloody puncture wounds.

He began sucking on the wounds, but instead of seeking further medical attention, he began recording the effects the venom was having on him.

4:30 - 5:30 PM strong nausea but without vomiting. During a trip to Homewood went on a suburban train.

5:30 - 6:30 PM strong chill and shaking followed by fever of 101.7. Bleeding of mucous membranes in the mouth began about 5:30, apparently mostly from gums.

8:30 PM ate two pieces of milk toast.

9:00 to 12:20 A.M. slept well. Urination at 12:20 AM mostly blood but a small amount.

DIARY OF A SNAKEBITE DEATH - Herpetologist Karl P. Schmidt

Took a glass of water at 4:30 AM, followed by violent nausea and vomiting, the contents of the stomach being the undigested supper. Felt much better and slept until 6:30 AM”

“September 26. 6:30 AM Temperature 98.2. Ate cereal and poached eggs on toast and apple sauce and coffee for breakfast. No urine with an ounce or so of blood about every three hours. Mouth and nose continuing to bleed, not excessively.”

“Excessively” was the last word Schmidt entered in his diary. After lunch, at about 1:30 p.m., he vomited and called his wife. By the time help arrived, Schmidt was unresponsive, covered in sweat, unable to talk. By 3 p.m. Schmidt was pronounced dead from “respiratory paralysis.”

According to Schmidt’s autopsy report, his lungs were bleeding, his eyes were bleeding, his heart, kidneys and brain were bleeding.

Boomslang venom acts quickly. Just .0006 milligrams of it can kill a bird in just a few minutes.