Monday, 10 March 2014

When the antivenoms don’t work, you gotta start asking questions

As a junior doctor in Australia, the country with the deadliest snakes and spiders in the world, you quickly learn where the antivenoms are kept. Now it appears that the deadliness of these critters is less than we thought, and the benefits of the anti-venoms are under question, or have been proven to be ineffective.

Last year, results from an Australian Government funded placebo-controlled trial was released that showed red-back spider antivenom to be ineffective. Despite personal experience and previous animal studies indicating that it was. The risk of an allergic reaction to this drug is 4-5%.

And when this (very Australian) story surfaced about a man bitten by an Eastern Brown snake I started looking into the evidence for the effectiveness of that particular antivenom too.

The recommendations
Regarding antivenoms, in a 2012 update the Australian Prescriber concludes that:
  • for red-bellied black snakes, “Early antivenom administration may prevent rhabdomyolysis, but it is unclear if this benefit outweighs the risk of adverse reactions to antivenom
  • repeated or larger initial doses of antivenom do not hasten recovery
  • and for the deadly box jellyfish (yes, we have a lot of deadly critters here), despite abundant laboratory (in vitro) evidence of its effectiveness, this antivenom “is an example where the difference between in vitro efficacy and clinical effectiveness is extreme. Although the antivenom is widely stocked in northern Australia, there have been at least four deaths despite antivenom administration. Conversely there has been survival after cardiac arrest, without antivenom, when cardiopulmonary resuscitation has been early and effective.
The current recommendations for snake bite are to give 1 vial of antivenom, but the limited clinical evidence is not very positive. I think that like many things (such as redback antivenom) , as more scientifically valid research is done, the effectiveness of snake antivenom will diminish.

Snake bite
Snake bite causes a coagulopathy – a blood coagulation disorder, and this is the problem. Clinically however, there has been some suspicion about the effectiveness of antivenom because it does not reverse the coagulopathy, initially resulting in larger and larger doses being given (up to 23 vials in this brown snake study). The current recommendations are to use 1 vial only, because more doses are ineffective, and this recommendation is based on lab evidence (that has not translated into clinical effectiveness for other antivenoms). This study showed that giving coagulation factors (FFP) was effective at treating snake bite coagulopathy, but the timing or dose of antivenom had no effect.

The language thing
Part of the problem is the language. The drugs we are talking about are called “antivenoms” so there is an automatic assumption that they are effective but, as usual, things are more complicated. Just because they bind with the venom in a lab, it doesn’t mean they save lives. For example, the cascade of effects initiated by the venom may happen quickly and may be difficult to reverse. There is also this niggling problem that their effectiveness has not been clinically proven (as opposed to laboratorily proven), that they do not appear to be effective in real cases, and that the one trial that has been done on the well-accepted redback spider antivenom showed it to be ineffective.

The numbers
There are up to 3,000 snake bites per year in Australia, of which about 1% get antivenom, but the deaths still number about 1 person per year.
The Australian Inland Taipan has been labelled the deadliest snake in the world, but there have never been any recorded deaths from this snake.
There has been no recorded death from spider bite in Australia since 1979.
Interestingly, this has been credited as due to the redback spider antivenom that has been shown to be ineffective (see above).
More people die each year in Australia from bee stings than snakes and spiders put together.
Anaphylactic (severe allergic) reactions to snake antivenom are common (here and here) and may be fatal.

The bottom line

The harms from spiders and snakes has been overestimated, the effectiveness of the antivenoms has been overestimated, and the harms of the antivenoms underestimated.

2 comments:

  1. I want to ask something...about venom...one of my friend have been bite by unknown snake...then, after a long time, he get poison from catfish...after this tragedy, be lost some of his finger and left foot

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