Category: Toxicology

We’re something of experts in spider bites in the Emergency Department. Black widow-type spider bites, however, are a little more exceptionally interesting than the average patient encounter. Latrodectism is usually nonfatal and easily managed with conservative treatment in the ED, although an immunoglobulin-based antivenom exists. Adverse effects from this antivenom are likely high-risk than any symptomatic benefit.

Now, a new antibody-fragment antivenom is vying for space on your formulary. In this study, 64 patients with clinical lactrodecism and significant baseline pain were randomized to either up to two doses of antivenin thirty minutes apart, or matching saline placebo. The primary outcome was “treatment failure”, a composite endpoint of failure to sufficiently decrease pain on the VAS scale, provision of a prescription analgesic, or a dose of the currently available antivenin.

Overall, the intervention met their predefined primary outcome – although, interestingly, half the antivenin cohort still had “treatment failure”. Then, almost a quarter of patients in the placebo cohort achieved full recovery. This remaining sliver of patients represents the measured effect size of the intervention – but the question remains the value and clinical relevance of their composite outcome. Mortality from lactrodectism is vanishingly low, and this intervention is not touted as being protective. Then, if the concern voiced by the authors is of short-term morbidity and ED recidivism in those whose pain is not adequately controlled without antivenom, then their primary, or at least a secondary outcome, ought to address this. Finally, the sample size is too small to draw any conclusion regarding safety.

This will undoubtedly be expensive and may likely expire in your hospital pharmacy prior to use. This trial gives us a small amount of information regarding its utility, but there’s little clear value demonstrated here.

“The Efficacy of Antivenin Latrodectus (Black Widow) Equine Immune F(abʹ)2 Versus Placebo in the Treatment of Latrodectism: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial”

https://www.sciencedirect.com/science/article/pii/S019606441930109X

Hyperbaric oxygen therapy is easily as controversial a topic in Emergency Medicine as any. Many physicians and scientists believe HBOT is an essential treatment for carbon monoxide poisoning, with a goal toward restoring normal intracellular physiology as rapidly as possible. Other skeptics, however, point to the paucity of high-quality evidence in support of a logistically complex and expensive intervention.

This is a retrospective review from Taiwan evaluating outcomes of 25,737 patients recorded in their national health database as suffering from carbon monoxide poisoning. Of these, 7,278 patients received HBOT while the remaining 18,459. There were many significant and relevant differences between cohorts, with those not receiving HBOT tending to be older and have more medical comorbidities. On this substrate, unsurprisingly, the authors find a survival advantage – persisting through multivariate statistical adjustment – to receiving HBOT, with an adjusted hazard ratio of 0.74 (95% CI 0.67-0.81).

Despite the size of their sample, it is unlikely these data reflect a true treatment effect from HBOT. In a retrospective cohort such as this, the pervasive differences between groups almost certainly suggests confounding features influencing treatment decisions. Off the limited structured data recorded in this database, it is unlikely any statistical adjustment or matching technique will provide a better reliable estimate of any true mortality benefit – nor is a mortality benefit one of the expected outcomes of HBOT.

The authors also spend some time reporting the survival advantages associated with receiving HBOT more than once over the first month following the poisoning event. These positive findings are, effectively, the definition of survivorship bias – mortality directly affects the ability to receive multiple treatments. You can’t dive the dead, of course, so simply surviving to undergo additional treatments is erroneously associated with a benefit.

The authors eventually state “The results provide important references for decision making in the treatment of COP” – but, unfortunately, they tell us very little. The level of evidence supporting or refuting treatment with HBOT remains poor until an RCT of sufficient scale can be performed.

“Hyperbaric oxygen therapy is associated with lower short- and long-term mortality in patients with carbon monoxide poisoning”
https://www.ncbi.nlm.nih.gov/pubmed/28427969

We’ve seen cured meat as a lifesaver – a last-resort hemostatic agent for refractory epistaxis. But, cured meat has a dark side, as well.

In this case report, a father and daughter arrive to the Emergency Departent short of breath, cyanotic, and hypoxic after ingesting “beef jerky”. Poisoned! But how?

This family had prepared their own, homemade beef jerky – and inadvertently oversalted the meat. In this case, the salt – sodium nitrate – resulted in methemoglobinemia. Rather than use 0.05 ounces of sodium nitrate to 5lbs. of food consistent with food preparation guidelines, these folks unwittingly added a full 1 ounce. This twenty-fold overdose resulted in methemoglobin levels >30% in each. Both recovered after treatment with methylene blue.

Other foods previously implicated in inadvertent sodium nitrate poisoning: blood sausage, kosher sausage, and bamboo shoot soup.

“The Beef Jerky Blues: Methemoglobinemia From Home Cured Meat”
https://www.ncbi.nlm.nih.gov/pubmed/27749634

When you drink sewage, it’s pretty clear what you’re getting: sewage, with all the expect, overt nutritional implications.

When you eat fruit, you expect a tasty and healthy meal.

Unfortunately, as this proof-of-concept study reveals, when you eat fruit watered by sewage, you get a little from Column A and a little from Column B.

This study conducted in Israel evaluated the presence of carbamazapine in healthy university student volunteers.  As carbamazapine is recognized to be excreted as an unchanged active drug, it is ubiquitous in untreated sewage – read “wastewater”.  Half the recruited students were then randomized to eat a selection of vegetables acquired from producers watering their fields with wastewater, rather than treated or fresh water.  Unsurprisingly, the various vegetables and leafy greens from the wastewater farm had elevated levels of carbamazepine – and so did the participants randomized to that group.

Just a happy thought for the day – and a reason to think ever so slightly more about from where your food’s water comes.

“Human Exposure to Wastewater-Derived Pharmaceuticals in Fresh Produce: A Randomized Controlled Trial Focusing on Carbamazepine”
http://pubs.acs.org/doi/abs/10.1021/acs.est.5b06256

Can you name some of your favorite types of patients in the Emergency Department?  Weak and dizzy?  Syncope?  Low back pain?  How about gastroparesis or cyclic vomiting syndromes?

Well, good news – if drug-induced vomiting is on your list of rewarding patient encounters, then this wave of states with newly legalized marijuana is just for you.

This is a small review of two urban, academic Emergency Departments in Colorado, retrospectively analyzing their diagnoses for encounters involving nausea & vomiting.  The breakpoint in their analysis was the legalization of recreational marijuana in 2009.  Through, frankly, a great number of assumptions involving documentation, drug screens, and other chart review calisthenics, the authors distilled out the patients with multiple ED visits for vomiting associated with drug abuse – clinically, the cyclic vomiting syndrome.  And, if you accept the limitations of their review: the number of visits for cyclic vomiting to their EDs has doubled since the introduction of legalized marijuana.

Hooray.

Interestingly, there is also a small exploratory analysis included in the paper regarding the antiemetic of choice.  They note promethazine use, despite the small sample, was significantly associated with needing admission – with an OR of 5.06 (95% CI 2.01 to 13.63).  Whether this represents unmeasured cofounders or a real effect is uncertain.  Anecdotally, with some evidence to support the practice, I have good experiences with droperidol and haloperidol in these sorts of patients.

“Cyclic Vomiting Presentations Following Marijuana Liberalization in Colorado”
http://www.ncbi.nlm.nih.gov/pubmed/25903855

For Labor Day, I referenced an article regarding the temporal patterns of pediatric traumatic injury – showing Labor Day, above all, was the most dangerous of holidays.

However, conversely, Thanksgiving may have one of the lowest rates of self-injury of all the major holidays.  These authors reviewed the rates of calls to poison control for suspected suicide attempts and found, compared with control days, essentially only New Year’s Day had consistently, and statistically, increased incidence of suicide attempts by poison.  In contrast, Independence Day, Thanksgiving, and Christmas were consistently, and statistically, lower than the control days.  Other major holidays were, essentially, a wash.

So, enjoy the protective effect against self-harm of this holiday season!

“Variation in Suicide Occurrence by Day and during Major American Holidays”
http://www.ncbi.nlm.nih.gov/pubmed/24462023

It is, again, the time of year when the temperatures drop precipitously – and, so, it is again the time of year to expand the differential for atraumatic headache to include carbon monoxide poisoning.  With records already being broken in Southern states unused to such temperatures in November, this message comes earlier than usual.

And, as a reminder, there is essentially no usable evidence describing the use of hyperbaric oxygen therapy for acute CO poisoning.

The most recent Cochrane Review, from 2011, covers six studies regarding the efficacy of HBOT as compared to normobaric oxygen therapy.  And, regrettably, all have serious methodologic flaws and potential for bias.  Four of these trials are absolutely negative, with trivial differences in outcomes between the two arms.  Two trials favor HBOT – a 60-patient trial published by Thom in 1995, and the seminal 152-patient trial presented by Weaver in the NEJM in 2002.  All told, the pooled effect of HBOT on short-term neurologic sequelae provides a protective effect with an OR of 0.78 – but with a confidence interval crossing unity (0.54 to 1.12).

Thus, these data neither support nor refute the utility of HBOT for treatment acute carbon monoxide poisoning – and provide no insight into appropriate patient selection.  What is most likely, given these results, is there is a cohort of patients for whom some benefit is observed.  Probably the most reasonable patients to select for treatment include those with the most severe poisoning and who can receive treatment immediately – but, otherwise, expect extraordinarily low-yield resource utilization to attempt treatment in the remainder.

“Hyperbaric oxygen for carbon monoxide poisoning (Review)”
http://www.ncbi.nlm.nih.gov/pubmed/21491385