A lecture on the use of Israeli antivenom in managing snake bites caused by Palestine viper (Vipera palaestinae), extracted from an Israeli article. A journal club presented as part of the residency program at Istishari Arab Hospital

1. Evaluation of Antivenom
Therapy for Vipera palaestinae
Bites in Children: Experience of
Two Large, Tertiary Care
Pediatric Hospitals
Prepared by: Hasan Arafat, MD
Supervised by: Amjad Rajab, MD
Department of Pediatric & Neonatology, Istishari Arab Hospital

2. Background
• There are three prevalent venomous snake families in the region of
Palestine, these have eight different species
• Atractaspis engaddensis ‫الخبيث‬ ‫األسود‬
• Cerastes cerastes ‫القرون‬ ‫أم‬ ‫األفعى‬
• Pseudocerastes fieldi ‫الجنايب‬ ‫أم‬
• Atractaspis ‫األسود‬ ‫الحنش‬
• Vipera berus ‫الشائعة‬ ‫الحية‬
• Cerastes vipera ‫قرع‬ ‫أبو‬
• Walterinnesia aegyptia ‫األسود‬ ‫الصل‬
• Vipera palasestinae‫فلسطين‬ ‫أفعى‬

3. Vipera palaestinae: Epidemiology
• The most common venomous snake in the region
• Typically found close to human habitat
• Feeds on mice and rats
• Although not the most venomous; it’s considered the most dangerous
due to its proximity to residential areas
• Since the introduction of specific antivenom therapy, the mortality
rate had decreased from 6-10% to 0.5-2%.

4. Vipera palaestinae: Appearance
• Triangular-shaped head
• Vertically elliptical pupils
• Characteristic fangs, rows of small teeth
• App. 1.35 m in length
• 1.5 kg in weight
• Color: varies

5. Vipera palaestinae: Venom
• Mainly enzymatic polypeptides
• Contains hemorrhagins, proteases, phospholipase A2, hyaluronidase,
esterases, phosphodiesterase, L-aminoacid oxidase
• Effects of these enzymes are both local and systemic
• A combination of necrotizing, hemotoxic, neurotoxic, nephrotoxic,
and/or cardiotoxic
• Also contains angioneurin growth factors and different integrin
inhibitors: future pharmacological benifits

6. Vipera palaestinae: Clinical Manifestations
Depend on many factors:
• Number of bites
• Depth of envenomation
• Potency and amount of venom injected
• Sie and underlying health of the victim
• Location of the bite
• Effectiveness of initial therapy

7. Vipera palastinae: General Principals
• Transportation to a medical facility familiar with the treatment of
snake bites is paramount
• Determine the site of bite
• General principals: immobilization, observation and supportive
measures
• Puncture wounds + no local swelling: observe for 8-12 hours, if no
swelling develops and labs remain normal, discharge
• Tourniquets, lymphatic-restricting bandages, GCS: not recommended

8. Vipera palaestinae: Antivenom
• Effective against both systemic and local signs if given within the an
adequate timeframe
• Clinical manifestations vary, progressive local signs are associated
with high morbidity and mortality,
• Administration in children follows the same guidelines as adults
• Dosses are based on clinical presentation rather than weight
• Consultation with a physician specializing in envenomation is
recommended

9. Study Objective
• Evaluate the fixed dose of V. palaestinae monovalent (equine)
immunoglobulin (Ig) G antivenom regimen used in two pediatric
emergency departments: Chaim Sheba Medical Center and Kaplan
Medical Center
• Particularly, assessing the need for repeated antivenom
administration and the rate of adverse effects in children

10. Methods
• A retrospective study of all children admitted with sings of V.
palaestinae envenomation between 1 March 2008 and 1 March 2014
to the Chaim Sheba Medical Center and Kaplan Medical Center
• Demographic info, clinical data, lab data, complications, morbidity
and mortality were extracted and recorded from medical charts.
• Diagnosis was established by history, identification of the snake, and
by comparison with a photograph

11. Methods
• Charts were reviewed and analyzed for the date of bite, patient age
and gender, geographical area, time elapsed since bite, affected limb,
systemic and local manifestations, and abnormal labs (coagulopathy,
thrombocytopenia).
• Indication, time to therapy, dose and adverse effects of antivenom
were recorded
• Data were abstracted onto a uniform data for by a single investigator
from each institute, who was not blinded to the objective

12. Methods: Definitions
The severity of bite was graded using the following criteria
• None (dry bite): fang marks may be seen, but no local or systemic
symptoms after 8-12 hours
• Minimal: only local involvement (pain, edema, blisters and
subcutaneous hematomas) confined to the site of the bite
• Moderate: swelling progressing beyond the site of the bite with some
systemic effects such as abdominal pain, vomiting, diarrhea and/or
lab abnormalities
• Severe: a state of hemodynamic shock (systolic BP <5th percentile)

13. Methods: Definitions
PALS parameters for tachycardia and hypotension were employed
• 1-2 years: 98-140 bpm
• 3-5 years: 80-120 bpm
• 6-11 years: 75-118 bpm
• 12-15 years: 60-110
• More than 16 years: >100 bpm
• Hypotension: systolic BP <5th percentile for age

14. Methods: Definitions
Control of envenomation:
• Cessation of progression of local swelling
• Cessation of systemic sings and symptoms
• Normalization of coags and thrombocytopenia

15. Methods: Definitions
• Demographic and clinical features were showed as number or
percentages for categorical variables and as the median and the 25th
and 75th percentiles for continuous variables
• Statistical comparisons of variables were done using non-parametric
association tests (Chi-square or Fisher’s exact test)
• p<0.05 indicates significance

16. Methods: Treatment Protocol
• For systemic signs and symptoms and progressive local effects caused
by V. palaestinae venom, administer 50 mL IV of antivenom
• Some patients included in the study received 30 mL in deviation from
protocol
• The antivenom is mixed in 250-500 mL of 0.9% normal saline,
administered over 1-2 hours.
• If the patient is in cardiovascular collapse or suffering a life-
threatening toxicity; treat aggressively with a starting dose of 80-120
mL
• Administer additional 30 mL if local manifestations progress or
systemic signs recur

17. Results

18. Results

19. Results

20. Results

21. Discussion
• V. palaestinae can be encountered from the eastern border with
Jordan to the city of Beersheba in the south and to the border with
Syria in the north
• Even if the snake is not available after a bite, the geographic area can
give a clue as to which snake is involved.
• A bite from a venomous snake is a medical emergency, involving the
affected site and potentially multiple organ systems.
• Many of our patients received antivenom despite not fulfilling criteria
for its administartion

22. Discussion
• The local effects of V. palaestinae venom, such as intense pain and
tense swelling, may mimic the signs and symptoms of compartment
syndrome
• Subfacial pressure measuring tools might not be present in many
centers, needing to misdiagnosis and unnecessary surgery, happened
with 2 of our patients

23. Discussion
• Venom-induced effects on the hematologic system may be present
despite a paucity of other local or systemic effects
• 1 patient developed thrombocytopenia
• 3 patients manifested mild coagulopathy

24. Discussion
• Aside from immediate resuscitation and support, management of
snake bites is based on the parenteral administration of animal-
derived antivenom.
• V. palaestinae antivenom is derived from foreign proteins and is
capable of producing acute and delayed hypersensitivity reactions in
humans
• Effective and timely antivenom administration reduces the impact of
snakebite mortality and morbidity
• Physicians should be knowledgeable about the indications and pifulls
associated with its administration

25. Study Limitations
• Adverse reactions may have occurred but were not documented
• Not enough data were available to accurately calculate snakebite
severity score
• There is a strong correlation between the severity score and the
clinical condition
• The abstractors were not blinded
• The dose administered deviated in some patients from the protocol
• In some cases, snake type was only suggested based on the habitat
with no solid evidence

26. Conclusions
• Antivenom should be considered in patients with marked local signs,
systemic effects, or laboratory abnormalities
• Antivenom should be administered in a dose of 50 mL (5 vials) IV over
1-2 hours
• It rarely results in serum sickness or severe allergic reactions
• Repeat administration may be necessary in the case of progressive,
local sings or continued systemic effects