1. Instituto de Biologia do Exército, Rio de Janeiro, RJ. 2. Faculdade de Medicina,
Universidade Estadual do Amazonas, Manaus, AM. 3. Departamento Clínico,
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, AM.
Address to: Dr. Iran Mendonça da Silva. Travessa Laguna 12. Lírio do Vale,
69038-010 Manaus, AM, Brasil.
Phone: 55 92 2127-3496; Fax: 55 92 2127-3462
Received in 07/12/2010
Accepted in 19/09/2011
Revista da Sociedade Brasileira de Medicina Tropical 45(4):523-525, Jul-Aug, 2012
Comparative evaluation of adverse effects in the use of powder trivalent
antivenom and liquid antivenoms in Bothrops snake bites
Avaliação comparativa de efeitos adversos no uso do soro antiofídico trivalente liofilizado
e soros antiofídicos líquidos no acidente botrópico
Iran Mendonça da Silva1,2 and Antônio Magela Tavares3
Introduction: Snake bite, a problem in public health, generally occurs
where there is no electric power. Methods: A comparative clinical study
was conducted with 102 victims of Bothrops snake bite, from the State
of Amazonas, Brazil; 58 victims were treated with liofilizated trivalent
antivenom serum (SATL) and 44 victims treated with liquid bivalent and
monovalent antivenom serum (SAMBL). Results: 17% (10/58) of patients
presented adverse effects with the SATL and 25% (11/44) with the SAMBL.
Conclusions: There was no statistic difference in number of adverse effects
between the two types of snake bite antivenom.
Keywords: Bothrops. Antivenoms. Adverse effects.
Introdução: Acidente ofídico, problema de Saúde Pública, é mais
frequente onde não há energia elétrica. Métodos: Foi realizado estudo
clínico comparativo com 102 vítimas de acidente botrópico, do Estado
do Amazonas, Brasil; 58 vítimas tratadas com soro antiofídico trivalente
liofilizado (SATL) e 44 vítimas tratadas com soro antiofídico monovalente
e bivalente líquido (SAMBL). Resultados: A comparação entre os tipos de
soro demonstrou 17% (10/58) de indivíduos com eventos adversos com
o uso de SATL e 25% (11/44) com o uso dos SAMBL. Conclusões: Não
houve diferença estatística na quantidade de reações adversas entre os dois
tipos de soros antiofídicos.
Palavras-chaves: Bothrops. Soro antiofídico. Efeitos adversos.
In Brazil, snake bite is a problem in public health1; generally,
it occurs where there is no electric power, far from hospitals, for
example, in forests of the Amazon Region, in field activities, and in
communities of people of indigenous origin2-4, where this study was
conducted. The registers of the Brazilian Health Ministry list about
20,000 victims of snake bite per year in the Brazilian territory. This
statistic number is not exact, as many snake bites occur where there
is no health unit to handle the notification. Many times, the victims
allow the snake bites to naturally heal without antivenoms and in
some cases with significant complications5-7. They lose fingers, legs,
hands, and arms, and they cannot work as well as they could before
the snake bite. They have serious complications such as infections,
kidney failure and death8. In these distant regions, because of the lack
of electric power, it is impossible to conserve the liquid antivenom in
low temperature between 20C and 80C, as recommended.
This evaluation is a clinical study to verify the safety of the
Brazilian powder trivalent antivenom compared with the Brazilian
liquid antivenom, made by the Butantan Institute, in the State of
São Paulo, Brazil and the Ezequiel Dias Foundation (Fundação
Ezequiel Dias - FUNED) and Vital Brazil Institute (Instituto
Vital Brasil - IVB). The powder trivalent antivenom was also
made in the Butantan Institute in association with the Biological
Institute of Brazilian Army, in Rio de Janeiro (Instituto de Biologia
do Exército - IBEx). Thus, Butantan Institute handled the final
industrial production and the IBEx performed the clinical study.
The SATL was produced by the Butantan Institute in
association with the IBEx. A prospective study was realized to
compare the adverse effects between two antivenoms. During
the 6 years of comparative study, the powder antivenom was
revalidated after analysis and emission of the Butantan Institute
certification to perform the analysis without interruption. To be
considered for inclusion in the project, the patients had to have
only light to moderate snake bite damages. We considered that
during this phase, the severe envenoming could be a variable
to confuse the results. The participants in the study should not
be pregnant and had to be between 12 and 70 years of age; this
selection of age was to avoid the exclusion of victims in rural work5
and to exclude immunological vulnerability and others diseases
commonly found outside this range (i.e., those previous snake
bite treatments and who are free from allergic effects caused by
horsehairs and other horse proteins). In the case of the victims of
the Bothrops snake bite, the participants to be treated with liquid
or powered antivenom were chosen randomly after diagnosis
of envenoming, after explanation about the project and after
signing the informed consent form. The clinical experiment was
considered a simple blind study, that is, only the health workers
knew which antivenom was being used. The patients were not
informed; they knew only that they were participating in a project
comparing two kinds of antivenom. The protocol of this study was
approved by the Research Ethics Committee of the Army Biology
Institute (Instituto de Biologia do Exército), Rio de Janeiro, and it
was sent to National Ethical Committee. The guidelines for human
experimentation of the National Health Council were followed in
the conduct of clinical research. The Pearsons χ2 test was used to
statistic analysis of results9. The patients were treated in Dr. Heitor
Vieira Dourado - Tropical Medicine Foundation (Fundação de
Medicina Tropical Dr. Heitor Vieira Dourado - FMT-HVD).
Silva IM and Tavares AM - Adverse effects of powder and liquid antivenoms in Bothrops snake bites
The authors declare that there is no conflict of interest.
CONFLICT OF INTEREST
After the use of antagonists of alpha-1 and alpha-2
receptors (cimetidine 300mg IV and dexchlorpheniramine
10ml oral route and hydrocortisone 500mg IV), according
to snake bite degree (e.g., light snake bite = two flasks of
SATL or four to six ampoules of SAMBL; moderate snake
bite = four flasks of SATL or eight to twelve ampoules of
SAMBL), the antivenom injection was done under medical
supervision to permit the detection of adverse effects, in
accordance to the objective of this study. The snake bite
victims were hospitalized for a period of 24h or more.
After this, if there were no complications to justify further
confinement in the hospital, the victim was sent home
with instructions to return on the seventh day and after the
fifteenth day after the snake bite. On those occasions, they
were evaluated for delayed adverse effects. The quantitative
and qualitative registers of detected effects were presented
by graphs of comparative analysis between the SATL and
the SAMBL (Figure 1).
The distribution of snake bite victims according by
characteristic of antivenom was 57% (58/102) to SATL
and 43% (44/102) to SAMBL, the ratio of patients were
equals (0.5) to both groups of patients, SATL (p-value=0.09,
CI=95%) and SAMBL (p-value=0.9, CI=95%).
When the adverse effects between the antivenoms are
compared, there are 17% (n=58) of persons with adverse
effects with the SATL and 25% (n=44) with the SAMBL
(p-value=0.47, CI=99%), the ratio of adverse effects is equal
to both in statistic analysis. Although the total number of
evaluated victims is only 102 persons, it is possible to say that
to this moment (Project Phase II) and in these cases, that the
SATL is as safe as SAMBL because had no statistic difference
in number of adverse effects between the two antivenoms,
as described in Figure 2 . The more frequent adverse effects
with the SATL were urticaria, pruritus, facial rubor and
vomiting; with the SAMBL the more frequent adverse effects
were pruritus, urticaria, vomiting and headache (Figure 1).
In according of literature10-12, the adverse effects presented
in this study were expected to occur and could be controlled
with other medicines, as soon as they appeared. It was not
reason to stop the treatment with both antivenoms (SATL
and SAMBL). To urticaria it was 31.3% with SATL and 30.8%
with SAMBL (p-value=1), to pruritus it was 25% with SATL and
38.5% with SAMBL (p-value=0.58) and to others adverse effects
it was 43.8% to SATL and 30.8% to SAMBL (p-value=0.63), there
was no statistic significance between the two, although there was
good tolerance to both antivenoms (Figure 2).
There were no more adverse effects in the SATL, which was
made with three different immunoglobulins, in agreement with the
experiences in India13. We believed that this antivenom can be used
when the genus of snake is not known. In the economic aspect, it is
clear that the SATL is better than the SAMBL, as it could be used
until eight years, eleven months and seven days after fabrication,
after revalidation of the study. The SATL was safe for the Bothrops
snake bite. The epidemiological, clinical and therapeutic aspects were
studied, and the SATL is viable with priority to the regions where
access is difficult due to the long distances from the public health unit.
Every patient who used the SATL went home without complications
and as evaluated until 15 days after the specific therapy. There was
FIGURE 1 - Distribution of adverse effects by type of antivenom (SAMBL and SATL).
SAMBL: liquid bivalent and monovalent antivenom serum; SATL: liofilizated trivalent
FIGURE 2- Distribution of urticaria, pruritus and others adverse effects by type of
antivenom (SAMBL and SATL).
SAMBL: liquid bivalent and monovalent antivenom serum; SATL: liofilized trivalent antivenom
serum; NS: no significance
no difference in the safety between both antivenoms (SATL and
SAMBL). It is necessary to make the SATL in Brazil because it is
more economic for the government and is better to the people living
long distances from the public health unit. The SATL was used for
almost nine years after its production and the SAMBL used until
three years after the efficacy was determined.
The principal objective is to the Amazon Region, where there are
important epidemiological characteristics, such as when the public
health unit is far from the primary forest and agriculture regions, when
there is no electric power to conserve the liquid antivenom in cold
temperatures (20C to 80C), and because there are the three genera of
snakes (Chrotalus, Bothrops and Lachesis) in the Amazon Region and
sometimes it is difficult to distinguish the snake after the bite.
Rev Soc Bras Med Trop 45(4):523-525, Jul-Aug, 2012
Instituto de Biologia do Exército, Rio de Janeiro, RJ.
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