Antivenom efficacy or effectiveness

The Australian experience

Geoffrey Isbister

    Research output: Contribution to journalComment/debateResearch

    Abstract

    Despite widespread use of antivenoms, many questions remain about their effectiveness in the clinical setting. The almost universal acceptance of their value is based mainly on in vitro studies, animal studies and human observational studies. Numerous examples exist where they demonstrate clear benefit, such as consumption coagulopathy in viper envenoming, prevention of neurotoxicity in Australasian elapid bites, systemic effects in scorpion and funnel-web spider envenoming. There are also concerns about the quality and efficacy of some antivenoms. However, it is important not to confuse the efficacy of antivenom, defined as its ability to bind and neutralise venom-mediated effects under ideal conditions, and the effectiveness of antivenom, defined as its ability to reverse or prevent envenoming in human cases. There are numerous potential reasons for antivenom failure in human envenoming, of which antivenom inefficacy is only one. Other important reasons include venom-mediated effects being irreversible, antivenom being unable to reach the site of toxin-mediated injury, or the rapidity of onset of venom-mediated effects. A number of recent studies in Australia bring into question the effectiveness of some antivenoms, including snake antivenom for coagulopathy, redback spider and box jellyfish antivenoms. Despite brown snake antivenom being able to neutralise venom induced clotting in vitro, use of the antivenom in human envenoming does not appear to change the time course of coagulopathy. However, it is important that apparent antivenom ineffectiveness in specific cases is correctly interpreted and does not lead to a universal belief that antivenom is ineffective. It should rather encourage further studies to investigate the underlying pathophysiology of envenoming, the pharmacokinetics of venoms and antivenoms, and ultimately the effectiveness of antivenom based on snake type, clinical effects and timing of administration.
    Original languageEnglish
    Pages (from-to)148-154
    Number of pages7
    JournalToxicology
    Volume268
    Issue number3
    DOIs
    Publication statusPublished - 9 Feb 2010

    Fingerprint

    Antivenins
    Venoms
    Snakes
    Spiders
    Cubozoa
    Scorpions
    Pharmacokinetics
    Disseminated Intravascular Coagulation

    Cite this

    Isbister, Geoffrey. / Antivenom efficacy or effectiveness : The Australian experience. In: Toxicology. 2010 ; Vol. 268, No. 3. pp. 148-154.
    @article{94d0a1b37084430293a1fd55b07d4265,
    title = "Antivenom efficacy or effectiveness: The Australian experience",
    abstract = "Despite widespread use of antivenoms, many questions remain about their effectiveness in the clinical setting. The almost universal acceptance of their value is based mainly on in vitro studies, animal studies and human observational studies. Numerous examples exist where they demonstrate clear benefit, such as consumption coagulopathy in viper envenoming, prevention of neurotoxicity in Australasian elapid bites, systemic effects in scorpion and funnel-web spider envenoming. There are also concerns about the quality and efficacy of some antivenoms. However, it is important not to confuse the efficacy of antivenom, defined as its ability to bind and neutralise venom-mediated effects under ideal conditions, and the effectiveness of antivenom, defined as its ability to reverse or prevent envenoming in human cases. There are numerous potential reasons for antivenom failure in human envenoming, of which antivenom inefficacy is only one. Other important reasons include venom-mediated effects being irreversible, antivenom being unable to reach the site of toxin-mediated injury, or the rapidity of onset of venom-mediated effects. A number of recent studies in Australia bring into question the effectiveness of some antivenoms, including snake antivenom for coagulopathy, redback spider and box jellyfish antivenoms. Despite brown snake antivenom being able to neutralise venom induced clotting in vitro, use of the antivenom in human envenoming does not appear to change the time course of coagulopathy. However, it is important that apparent antivenom ineffectiveness in specific cases is correctly interpreted and does not lead to a universal belief that antivenom is ineffective. It should rather encourage further studies to investigate the underlying pathophysiology of envenoming, the pharmacokinetics of venoms and antivenoms, and ultimately the effectiveness of antivenom based on snake type, clinical effects and timing of administration.",
    keywords = "antiserum, placebo, scorpion venom, snake venom, snake venom antiserum, spider venom, spider venom antiserum, Australia, blood clotting disorder, clinical trial, drug efficacy, drug mechanism, drug treatment failure, envenomation, human, neurotoxicity, nonhuman, poisonous scorpion, poisonous snake, poisonous spider, primary prevention, priority journal, recommended drug dose, review, snakebite, Animals, Antivenins, Arachnidism, Bites and Stings, Blood Coagulation Disorders, Cnidarian Venoms, Elapid Venoms, Humans, Snake Bites, Snake Venoms, Treatment Outcome, Animalia, Cubozoa, Dipluridae, Elapidae, Latrodectus hasselti, Scorpiones, Storeria dekayi, Viperinae",
    author = "Geoffrey Isbister",
    year = "2010",
    month = "2",
    day = "9",
    doi = "10.1016/j.tox.2009.09.013",
    language = "English",
    volume = "268",
    pages = "148--154",
    journal = "Toxicology",
    issn = "0300-483X",
    publisher = "Elsevier",
    number = "3",

    }

    Antivenom efficacy or effectiveness : The Australian experience. / Isbister, Geoffrey.

    In: Toxicology, Vol. 268, No. 3, 09.02.2010, p. 148-154.

    Research output: Contribution to journalComment/debateResearch

    TY - JOUR

    T1 - Antivenom efficacy or effectiveness

    T2 - The Australian experience

    AU - Isbister, Geoffrey

    PY - 2010/2/9

    Y1 - 2010/2/9

    N2 - Despite widespread use of antivenoms, many questions remain about their effectiveness in the clinical setting. The almost universal acceptance of their value is based mainly on in vitro studies, animal studies and human observational studies. Numerous examples exist where they demonstrate clear benefit, such as consumption coagulopathy in viper envenoming, prevention of neurotoxicity in Australasian elapid bites, systemic effects in scorpion and funnel-web spider envenoming. There are also concerns about the quality and efficacy of some antivenoms. However, it is important not to confuse the efficacy of antivenom, defined as its ability to bind and neutralise venom-mediated effects under ideal conditions, and the effectiveness of antivenom, defined as its ability to reverse or prevent envenoming in human cases. There are numerous potential reasons for antivenom failure in human envenoming, of which antivenom inefficacy is only one. Other important reasons include venom-mediated effects being irreversible, antivenom being unable to reach the site of toxin-mediated injury, or the rapidity of onset of venom-mediated effects. A number of recent studies in Australia bring into question the effectiveness of some antivenoms, including snake antivenom for coagulopathy, redback spider and box jellyfish antivenoms. Despite brown snake antivenom being able to neutralise venom induced clotting in vitro, use of the antivenom in human envenoming does not appear to change the time course of coagulopathy. However, it is important that apparent antivenom ineffectiveness in specific cases is correctly interpreted and does not lead to a universal belief that antivenom is ineffective. It should rather encourage further studies to investigate the underlying pathophysiology of envenoming, the pharmacokinetics of venoms and antivenoms, and ultimately the effectiveness of antivenom based on snake type, clinical effects and timing of administration.

    AB - Despite widespread use of antivenoms, many questions remain about their effectiveness in the clinical setting. The almost universal acceptance of their value is based mainly on in vitro studies, animal studies and human observational studies. Numerous examples exist where they demonstrate clear benefit, such as consumption coagulopathy in viper envenoming, prevention of neurotoxicity in Australasian elapid bites, systemic effects in scorpion and funnel-web spider envenoming. There are also concerns about the quality and efficacy of some antivenoms. However, it is important not to confuse the efficacy of antivenom, defined as its ability to bind and neutralise venom-mediated effects under ideal conditions, and the effectiveness of antivenom, defined as its ability to reverse or prevent envenoming in human cases. There are numerous potential reasons for antivenom failure in human envenoming, of which antivenom inefficacy is only one. Other important reasons include venom-mediated effects being irreversible, antivenom being unable to reach the site of toxin-mediated injury, or the rapidity of onset of venom-mediated effects. A number of recent studies in Australia bring into question the effectiveness of some antivenoms, including snake antivenom for coagulopathy, redback spider and box jellyfish antivenoms. Despite brown snake antivenom being able to neutralise venom induced clotting in vitro, use of the antivenom in human envenoming does not appear to change the time course of coagulopathy. However, it is important that apparent antivenom ineffectiveness in specific cases is correctly interpreted and does not lead to a universal belief that antivenom is ineffective. It should rather encourage further studies to investigate the underlying pathophysiology of envenoming, the pharmacokinetics of venoms and antivenoms, and ultimately the effectiveness of antivenom based on snake type, clinical effects and timing of administration.

    KW - antiserum

    KW - placebo

    KW - scorpion venom

    KW - snake venom

    KW - snake venom antiserum

    KW - spider venom

    KW - spider venom antiserum

    KW - Australia

    KW - blood clotting disorder

    KW - clinical trial

    KW - drug efficacy

    KW - drug mechanism

    KW - drug treatment failure

    KW - envenomation

    KW - human

    KW - neurotoxicity

    KW - nonhuman

    KW - poisonous scorpion

    KW - poisonous snake

    KW - poisonous spider

    KW - primary prevention

    KW - priority journal

    KW - recommended drug dose

    KW - review

    KW - snakebite

    KW - Animals

    KW - Antivenins

    KW - Arachnidism

    KW - Bites and Stings

    KW - Blood Coagulation Disorders

    KW - Cnidarian Venoms

    KW - Elapid Venoms

    KW - Humans

    KW - Snake Bites

    KW - Snake Venoms

    KW - Treatment Outcome

    KW - Animalia

    KW - Cubozoa

    KW - Dipluridae

    KW - Elapidae

    KW - Latrodectus hasselti

    KW - Scorpiones

    KW - Storeria dekayi

    KW - Viperinae

    UR - http://www.scopus.com/inward/record.url?scp=77049107081&partnerID=8YFLogxK

    U2 - 10.1016/j.tox.2009.09.013

    DO - 10.1016/j.tox.2009.09.013

    M3 - Comment/debate

    VL - 268

    SP - 148

    EP - 154

    JO - Toxicology

    JF - Toxicology

    SN - 0300-483X

    IS - 3

    ER -