Snake oil for snakebites (and other bad ideas)

Spring is here.  I don’t say that because of the warmer weather, the blooming tulips in my back yard, or the current effect of the earth’s axial tilt on the Northern hemisphere.  No, in my somewhat warped world of the pediatric ICU seasons are marked by illnesses and injuries with an annual rhythm.  Fall begins with a spike in cases of bronchiolitis, Summer with a near-drowning in a swimming pool.  Winter has arrived when seasonal influenza reappears.  And Spring, well, Spring has several harbingers, including auto vs bicycle accidents, falls from windows, and snakebites.

Sure enough, this week we admitted our first child of the year bitten by a venomous snake who, like most people unfortunate enough to be envenomated by a North American pit viper, has done very well.  This child fell prey not only to our local limbless fauna, but also to one of several common myths or misunderstandings about snakebites that place the victim, rescuer, or both at higher risk for injury and complications.  This post will explore some of the more common mistakes people make during North American snakebite encounters (being limited to snakes native to North America, the following does not necessarily apply to snakes from other areas).

File this post under Science-Based-You’re-Not-Helping-Please-Don’t-Do-That.

Myth #1: You Need to Know the Species / Kill the Snake

North America has around 120 species of snake, over 20 of which are venomous.  With so many species, it may seem important to ID the snake so the docs in the ED can give the appropriate anti-venin.  Fortunately, that isn’t the case.

All venomous North American snakes fall into one of two families, the Elapidae, and the CrotalinaeCrotalinae encompasses most of the venomous species commonly encountered, including the Copperhead, the Cottonmouth (aka Water Moccasin), and all rattlesnakes.  Elapidae, on the other hand, is represented by only two species in North America, both a type of coral snake.

The close evolutionary relationship of these snakes (except the coral snake) means that the venom of all Crotalinae is very similar.  Venom is a mixture of a variety of different enzymatic proteins and low-molecular-weight polypeptides, in the case of Crotalinae including proteolytic enzymes, collagenase, hyaluronidase, phospholipases, RNase, DNase, phosphodiesterase, lactate dehydrogenase, a thrombin-like enzyme, and more.  It’s nasty stuff.

Though people have tried to label certain venoms as “hematotoxic” or “neurotoxic,” the sheer variety of proteins and their broad range of actions make this labeling somewhat misleading.  Symptoms and findings at the site of the bite include rapid swelling, bruising, pain, and erythema, while systemic symptoms include nausea, vomiting, oral paresthesias (odd sensations) including a metalic taste, low blood pressure, rapid heart rate and breathing, a markedly deranged ability of the blood to clot, kidney damage, altered levels of conciousness, weakness, double vision, and more.  The volume of venom and relative proportions of its component molecules vary species to species and snake to snake.  However, since the molecules themselves are so similar (and in many cases identical), a single antivenin is capable of treating the venom from all species within the family Crotalinae.

This fact mean clinicians need only ensure that the bite A) didn’t come from a zoo or private collection containing a non-North American venomous snake, and B) that it wasn’t a coral snake, before selecting which antivenin to administer.

How can a doc be sure someone wasn’t bitten by a coral snake?  After all, it does require a different and difficult to obtain antivenin from the Crotalinae. Here again we are assisted by happy chance.  Coral snakes have a very limited range, and can be ruled out in the majority of states.  In areas where the coral snake is endemic, it is easily identified by its red/yellow/black coloration at a distance.  Even an un-witnessed bite can frequently be distinguished by the symptoms and physical appearance of the bite on arrival.  Furthermore, coral snakebites while very serious are quite uncommon, making up only ~1% of venomous bites.

Physicians almost invariably have all the information they need to treat North American venomous snakebites from knowing the geographic location where the bite occurred and the patient’s history and physical exam.  No snake corpse is required or desired.

What’s the harm in killing the snake?  I’d think this was obvious were it not for the nearly ubiquitous element of snakebite histories that people went out of their way to kill the offending animal (the family this week did exactly that).  The risk of trying to kill a snake is that you can be bitten too.  Of all venomous snakebites, almost half occur while people are trying to kill a snake.  They place themselves at risk for no benefit to the person already bitten. Oh, and people will frequently then bring the “dead” snake in to the ED.  Is it dead?  Probably, but since the bite reflex can remain intact for a short time after death, I’d rather not risk my life on your skill as the Great White Hunter.

The best plan is to get everyone safely away from the snake and call animal control to get the animal away from your home, don’t try to do it yourself, and don’t bring it to the hospital.  Please.

Myth # 2: Most Snakebites are Rapidly Lethal

I remember speaking to a 12-year-old last year who was 2 days out from his bite and doing well, only to find that he still fully expected to die from the bite.  A snake, after all, had bitten him and snakebites kill you!  It broke my heart that I had allowed him to live with this fear for two days.

I should have anticipated his fear, because his reaction is not at all uncommon.  Most parents (and children old enough to know) are terrified when their child is bitten by a venomous snake.  Though entirely justified, their fears and expectations are usually out of proportion to the actual risk.

The lethality of a bite depends on a vast number of variables including the species and size of the snake, the location of the bite, the number, depth, and duration of bites, the first aid given, and the type and rapidity of medical care received.  In general, for Crotalinae envenomations not given antivenin the mortality is a very respectable 5-25%.

Antivenin (Crotalidae) Polyvalent (ACP) was the first antivenin introduced in 1954, and was produced by exposing horses to low doses of venom to induce antibodies against its component molecules.  IgG antibodies, including those now directed against the venom, were then purified from the horse’s blood and this was injected into humans bitten by Crotalinae species.  The antibodies then bind to the various proteins and enzymes in the venom, rendering them inert.  The use of this antivenin reduced the mortality rate from 5-25% down to 0.5%.

Though effective, ACP had a rather high incidence of anaphylaxis (20-25%) and serum sickness (~50%), driving the development of a better antivenin.  In 2000, CroFab was approved.  Derived from sheep serum, containing far less non-human protein, and being made of a Fab fragment, Crotalidae Polyvalent Immune Fab (Ovine) aka CroFab, has been far better tolerated.  Post-release studies have reported anaphylaxis or severe reactions in 0-19%, and serums sickness in 0-23%, and mortality rates are the lowest they have ever been.  CroFab is currently the only Crotalidae antivenin available.

Presently there are around 8000 venomous bites per year in the US, but less than 12 deaths per year, making current mortality ~0.15%, though another 15-40% of victims sustain some form of permanent injury or disfigurement.

In addition to the fact that most bites are from non-venomous snakes, there is another facet to snakebite lethality to think about: the concept of a  “dry bite,” or a bite from a venomous snake without injection of venom.  It’s surprisingly common, accounting for around 25% of Crotalinae bites and ~50% of coral snake bites.  Given the high rate of dry bites from venomous snakes, large number of bites from non-venomous snakes, and the rather high side-effect profile of even our newest antivenin, it’s reasonable to ask who should get antivenin.

If you have symptoms of envenomation, you need antivenin, period.  However, symptom onset can be delayed, occasionally by hours.  If someone arrives in the ED with a bite but no symptoms other than a couple of small holes, it is reasonable (and standard of care) to watch them in the ED without antivenin.  Should symptoms begin, antivenin should be started immediately, but if there are no symptoms after 12 hours, it is safe to declare the encounter a dry bite, the person lucky, and let them go home.

Remember, all snakebites should be taken seriously and brought to immediate medical attention, but most will not require antivenin, and even those who do will tend to recover well.

Myth # 3: Suck Out the Poison

I love this one.  The idea is self-apparent: venom is in me, I want venom out of me, suck it out through the holes.  You’ve seen it in countless Old West movies, and it still pops up in modern entertainment, older medical literature, and even some out of date professional sites.  There are devices currently marketed to apply a constant negative pressure (~ 1 atmosphere) to the wound and actually do produce fluid, purportedly containing venom, that is then discarded.  As recently as the early 2000’s, these devices were advocated for short durations of time as they were felt to hold some potential benefit but pose little risk of harm.  Time and study has not been kind to this recommendation.

First the question of efficacy.  After needle injection of a radio-labeled fluid into volunteers, one study attempted to then remove it by suction using a popular commercially available pump; they successfully removed only 0.04% of the simulated venom.  In another randomized, controlled study pigs were randomized to receive suction therapy or no suction following injection of real venom.  The suction pump effected no improvement in symptoms in the pigs.  The bulk of the evidence, sparse as it is, indicates that these devices do not work.

Beyond being ineffective, suction devices also cause quite a bit of damage.  Even on normal skin negative pressure quickly forms a “hickey,” which is a bruising and edema of the skin.  Combine that trauma with skin being actively destroyed by the venom, and you simply generate a worse wound without reducing the venom load.  This is precisely what was found in the porcine study discussed earlier, and has been reported in the literature since. Significant harm + no benefit = bad idea.

Suction applied by mouth is even worse.  Not only does it just as ineffective while carrying the same risk as the devices (maybe a bit less, since the suction isn’t sustained), but now you add the oral bacterial flora of the human mouth to a fresh wound.  Snakes’ mouths are far from sterile, but bacterial infections after snakebites are uncommon enough (<3%) that antibiotics are not routinely prescribed, unlike human bite wounds.  Don’t compound the problem by giving the victim cellulitis.

If you are bitten by a snake and someone tries to suck out the poison, kindly go ask them to catch the snake instead.*

* Don’t do that.  Just tell them to call 911.

Myth # 4: Place a Tourniquet

In older survival manuals it was common advice to apply a tourniquet around the bitten limb, the thought being to limit the venom’s spread and to provide time to get to medical care.

There has been at least one animal study that demonstrated a longer survival time in pigs after envenomation with the use of a tourniquet (36 min longer), providing some plausibility to the benefit of tourniquets after snakebites.  However, the same study also showed markedly elevated pressure in the effected limb (43 mmHg higher) and led the authors to discourage the use of tourniquets for snakebites. But better to lose a limb and save a life, right?  Well, yes, if it were effective at saving lives in practice.

The trouble is that in practice tourniquets are fiendishly tricky to apply without causing further injury, and even with training under controlled circumstances professionals aren’t able to place them to the “proper” pressure.  Furthermore, clinical studies have failed to confirm the modest benefit seen in one animal model while demonstrating multiple serious complications from their use (tourniquets too easily become ligatures and compound the injury of the venom).

Tourniquets have their place in medicine, but it isn’t in the management of a venomous snakebite.

Myth # 5: Apply Ice

One of the hallmarks of a Crotalinae envenomation is swelling, pain, bruising, and often a burning sensation.  This superficially resembles other traumatic injuries, like a badly twisted ankle commonly treated with ice packs, so it makes some sense people are inclined to try cooling a snakebite.

Though there is a degree of hyperemia (increased blood flow) with envenomations that ice will reduce, the swelling is due more to the direct tissue injury of the venom. That direct injury also causes increasing pressure, clotting, and vascular damage all of which impede and at times stop blood flow to the tissue.  Anything done that further reduces blood flow (like ice or tourniquets) can make such injuries much worse.  Animal modeling has failed to show a benefit from cooling of the injury, and clinical studies have suggested that people may have more complications if their bites are iced.

There is, of course, also the more obvious risk of ice, in that it tends to be rather cold, and can cause injury to even healthy tissue if not closely monitored.  Yet again, we have little hope of benefit with clear risk of harm.  No ice.

Myth # 6: Taze Me, Bro! (Electrotherapy)

In 1986 the Lancet published the first paper in the medical literature where Dr. Guderian advocated high voltage electric shock of the envenomated site as a first aid technique. Subsequent studies in both animals and humans failed to show any benefit, and there has not been any significant presence of this intervention in the medical literature since 2001, which was a paper condemning its use.

Of course, this hasn’t stopped people from adding insult to injury by tazing their buddies who were just struck by a rattlesnake.  Yes, really.  Let that image sink in for a moment… there you go.  Dr. Guderian, or someone posing as him, puts forth the argument for electrotherapy of envenomations here.  As this is already a lengthy post, I’ll address this gem of a site and its specific claims at a later time.  Suffice it to say that beyond a very crude form of pain control, electrotherapy holds no plausible benefit, has significant risk of harm (like electrocution and burns), and has the existing literature stacked firmly against it.

If you are bitten by a snake and someone tries to taze you, kindly go ask them to go catch and taze the snake instead.*

* Again, don’t do that.  Just tell them to call 911, then re-assess your choice of friends.

What You Should Do

Odds are that neither you nor anyone you know will ever be bitten by a snake.  However, if you happen to find yourself joining those unlucky few, the best things you can do are incredibly simple:

1)    Calm the victim and calm yourself.

2)    Call 911.

3)    Immobilize the limb like you would a fracture and await medical assistance.

4)    Report any symptoms, no matter how odd or minor, to medical providers immediately as they occur.

What if you are days out in the wilderness, is it worth trying these interventions in a desperate situation?  No.  Being away from help doesn’t make useless and harmful interventions any less useless or harmful.  Instead, be responsible and have an evacuation plan for any medical emergency, including snakebites.  Now go enjoy the Spring!

Posted in: Science and Medicine

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