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”
The new year – actually, the end of the old year – brings us a new update on the management of carbon monoxide poisoning, as distilled into an ACEP Clinical Policy statement. There are three elements to their update, addressing specific management questions in the context of carbon monoxide toxicity:
- Don’t rely exclusively on non-invasive means for CO measurement.
- Hyperbaric oxygen therapy is neither proven nor disproven of benefit.
- Cardiac testing provides useful prognostic information.
The most impactful recommendation of the three is the one for HBO therapy, which is either dismissed out-of-hand or pursued with such zealotry that eligible patients are airlifted to far-flung dive chambers for treatment. In theory, HBO therapy helps reduce the delayed neuropathology and cognitive burden related to lipid peroxidation and other toxic metabolites. However, these authors appropriately synthesize the low-quality evidence into a conclusion that HBO therapy has no proven advantage to high-flow oxygen.
As with any therapy for which the evidence is poor, there are proponents on both sides and substantial practice variation. This Clinical Policy does not state HBO is inappropriate or not beneficial for carbon monoxide poisoning, merely the evidence is inconclusive. Sometimes, when the evidence is insufficient to provide an answer, the magnitude of benefit is small or clinically unimportant. In this case, I’m not even sure such a conclusion regarding the scope of benefit can be made – the foundational evidence is simply too unreliable to make any practice-influencing recommendations.
“Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Acute Carbon Monoxide Poisoning”
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”
As our sepsis overlords entrenched new “quality measures” and other protocol-driven resuscitation requirements in our Emergency Departments, this article serves as a lovely reminder of the importance of staying cognitively engaged.
Lactate levels can be elevated by metabolic and microcirculatory derangements related to the spectrum of sepsis – but also other, non-infectious causes. These include hepatic disease, multiple toxodromes, and multiple medications – one of the most commonly used being beta-agonist therapy for obstructive airways. This very simple study examines the physiologic changes in healthy volunteers receiving 10mg of nebulized albuterol, as compared with nebulized saline. Placebo volunteers had no change in lactate or placebo. Albuterol receiving volunteers had an average increase in lactate of 0.77 mmol/L and an average decrease in potassium of 0.5 mEq/L. Lactate increases, however, were highly variable – ranging from 0.04 to 2.02 mmol/L.
These data aren’t perfectly generalizable to the critically or pseudo-critically ill, but they’re a reasonable starting point for a gross estimate. They’re also justification for reconsideration of potentially inappropriate therapies for an intermediate-range lactate that obstinately refuses to clear – in the context of receiving multiple rounds of nebulizers.
At the very least, it’s a reminder of the various exceptions to our protocols we need to consider to prevent costly and avoidable harms.
“The Effect of Nebulized Albuterol on Serum Lactate and Potassium in Healthy Subjects”
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”
The hazards of the natural world are not an issue for those of us born into “civilization”. Without lions, tigers, bears, and dingoes to endanger our babies, we’ve had to become more creative. Firearms in the home, detergent packets, and, now: highly concentrated nicotine from e-cigarettes. This short review provides a brief look at an increasingly prevalent health hazard.
The lethal dose of nicotine is approximately 1 mg/kg. Concentrations of liquid nicotine cartridges may be as high as 35 mg/mL. A typical 10 mL refill bottle, then, has easily a lethal dose for children, while a 50 mL bottle could have more than enough to bring down a horse. For comparison, a conventional cigarette contains 10 to 1 5mg of nicotine – certainly a danger, but on a different scale entirely.
The expected clinical effects are consistent with the classical nicotinic and muscarinic toxodromes – vomiting, diarrhea, salivation, bronchorrhea, seizures, rhabdomyolysis, and respiratory failure. Therapeutic management remains supportive – intravenous fluids, atropine, and mechanical ventilation as needed. Inadvertent exposures are typical, but liquid nicotine may also be used for intentional overdose in suicide attempts.
Another proud cultural innovation for the 21st century.
“Liquid Nicotine Toxicity”
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.
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”
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”
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)”
Children, rumor has it, are curious, persistent, and nefarious creatures. Furthermore, the entire natural environment must first be tasted. Thus, age-old cautionary guidance regarding home safety for children to prevent exposure to potentially hazardous materials.
So, naturally, laundry detergent would be kept safely out of reach of children – particularly the pre-packaged pod systems, which are candy-like and perfect for oral consumption – correct?
According to this data from the National Poison Data System, in just a single year, there were 17,230 calls for pediatric exposure to laundry detergent pods in just two years, between January 2012 and December 2013. The majority – 79.7% of cases – were secondary to ingestion. 4.4% of patients with an ingestion were judged to necessitate hospitalization, including 102 requiring intubation. One death was reported – but the autopsy showed intracranial bleeding of uncertain/unlikely relation to the ingestion of detergent.
The authors specifically call out Procter & Gamble, maker of Tide Pods, for failure to place adequate warning labels or safety latches on their packaging – although, frankly, the ultimate responsibility lay with parents. Keep cleaning supplies safely out of reach!
“Pediatric Exposure to Laundry Detergent Pods”