This one is for @drsamko, thanks to his tweet yesterday.
The most recent of 19 articles in pubmed for the search “sodium polystyrene sulfonate lithium”, a retrospective cohort review looking at the use of SPS in the treatment of lithium toxicity. Given that lithium and potassium are similarly charged cations, multiple animal studies evaluated its use in lithium overdose, but only case reports in humans. These authors reviewed 9 years of cases at their institutions, two hospitals in Montreal, Canada, for the effect on lithium serum half-life between patients prescribed SPS vs. patients who were not prescribed SPS.
They only looked at chronic overdoses admitted for management – 90 patients, 72 chronic, 48 had data points to properly evaluate the half-life. 36 received “standard treatment” and 12 were prescribed SPS. The authors don’t well-describe the standard treatment group, and don’t indicate whether any received hemodialysis – but I get the impression the treatment for chronic toxicity only employs HD on rare occasions of renal failure. Of the 12 that received SPS, most simply received IV hydration and observation in addition to SPS – and one received hemodialysis due to renal failure. Half-life of lithium in the controls was 43 hours compared to 20.5 hours in the SPS-receiving group.
SPS isn’t totally benign – there was mild hypokalemia in half their treatment population – and in rare cases it causes intestinal necrosis. And, considering chronic lithium toxicity generally has a benign course, you could go either way. You can certainly argue that decreased hospital length-of-stay is a significant financial and health benefit and justify giving it, though, so it’s worth knowing about.
“Successful treatment of lithium toxicity with sodium polystyrene sulfonate: a retrospective cohort study”
www.ncbi.nlm.nih.gov/pubmed/19842945
Category: Toxicology
N-acetylcysteine Overdose With Anaphylactoid Reaction and Myocardial Infarction
This is another toxicology case that illustrates a point I make (probably too often) to my residents – that every action we take has a risk of harm, whether known or unanticipated. I’m probably the only attending who cancels their IM ketorolac orders and changes them to PO ibuprofen. Why? Because of cases like this.
This is an entirely appropriate therapy – N-acetylcysteine given for hydrocodone-acetaminophen overdose – gone wrong because of a mixing error resulting in 10-fold overdose (126,000mg loading dose!). Anaphylactoid reactions are known side effects in N-acetylcysteine, and, unfortunately, this patient’s reaction was more severe than most, suffering an inferior MI with a peak troponin of 658ng/mL. He expired 17 hour after the N-acetylcysteine overdose.
I’ve seen epinephrine given IV instead of SQ more than once (one time resulting in an MI), many medications are tissue toxic if they extravasate, you can get sterile abscess formation from intramuscular injections, etc. The fewer interventions and the less invasive the interventions, the less risk at which we place our patients.
“Fatal myocardial infarction associated with intravenous N-acetylcysteine error”
Ethanol Hand Sanitizer Abuse
I imagine every department has a frequent-flier patient like this – they keep getting referred to rehab, but they don’t stop bouncing back. And the hand cleanser keeps mysteriously running out.
This is case report and literature review of the National Poison Data System that documents the accidental and intentional exposures to ethanol-containing hand sanitizer. And, really, their numbers probably underestimate the issue – considering the cases reported to poison control are primarily in children under age 6. There are plenty of teenagers and other adults abusing these substances as well, but they are far less likely to be reported to a poison control center.
The case report is rather amusing – a teenager with a g-tube “looking for a buzz” who put 500mL of 61% ethanol hand sanitizer into the tube and subsequently required intubation and then dialysis when his first ethanol level was 720mg/dL.
“The rising incidence of intentional ingestion of ethanol-containing hand sanitizers”
www.ncbi.nlm.nih.gov/pubmed/21926580
Hyperbaric Oxygen Therapy for Carbon Monoxide
Another mini-review where I agree with the Cochrane Review that essentially concludes: too much cost/risk, not enough proven benefit.
Hyperbaric oxygen therapy is of proven value in rapidly clearing carboxyhemoglobin from the serum – half-life approaches 20 minutes at 3 atmospheres vs. 1 hour on 100% face mask and several hours at lower concentrations of oxygen. In addition, HBO has all sorts of beneficial effects in terms of preventing the damaging intracellular effects of carbon monoxide, including impairment of cytochrome oxidase a3 and of lipid peroxidation. Lipid peroxidation, as you might imagine, in a brain full of lipids, is where you really end up in trouble with permanent neurologic sequelae.
Unfortunately, the first animal models that prove how well HBO works go directly from CO poisoning into multiple atmospheres of therapy. As few HBO centers there are in the U.S., this is absolutely not a clinically relevant model because of the delays to therapy – and that’s why the human literature is less conclusive.
There are essentially three large studies that contribute most of the weight to the 2011 Cochrane Review – one from 1989 that demonstrates no benefit, a second from 2002 in the New England Journal of Medicine that has a broad following, and, finally, a 2011 publication in Intensive Care Medicine. Most toxicologists who are pro-HBO base their opinions on the 2002 Weaver article.
The good news about the Weaver article – it’s a great study. It enrolls a lot of patients, it enrolls all kinds of patients, it dives them to three atmospheres, it does three dives in a 24 hour period, and it has excellent objective testing and subjective evaluation follow-up. This study was well-designed to give us the answers. And, in the end, it finds a significant difference in objective neurologic function in the HBO group and a subjective difference in memory ability in the HBO group. What is odd, however, is that there were many objective tests of cognitive function. Most trended towards favoring the HBO group, but only one of them reached statistical significance – a trail marking test in which a line was drawn between similar numbers. The absolute change in cognitive function between treatment and follow-up wasn’t that much different between the two groups. And, unfortunately, the larger issue for me is the baseline difference between the two groups in amount of time exposed to CO which trended towards much higher in the NBO group – 22 +/- 64 hours in the NBO group and 13 +/- 41 hours in the HBO group.
This difference is much more important because animal studies have demonstrated it’s not the carboxyhemoglobin concentration that matters as much as the dissolved CO that diffuses intracellularly. There’s a fabulous study in dogs demonstrating this difference. In one group, they exposed dogs to CO to get their carboxyhemoglobin concentration to 68% – and they all died. In a second group, they bled dogs until they had lost 68% of their hemoglobin – in theory, the same level of deoxygenation as the CO group – and they all lived. Third, they bled dogs down until they had lost 68% of their hemoglobin, then exposed that hemoglobin to CO in vitro and re-transfused it back into the dogs – in theory, the same 68% carboxyhemoglobin level as group 1 – and those dogs lived. The difference between group 1 and 3 was the amount of dissolved CO in the blood and intracelluarly, and it was demonstrated that their cytochrome oxidase a3 activity was normal in group 3 despite the carboxyhemoglobin levels.
So, that’s where I can’t take the Weaver evidence as strong enough as the sole large study favoring HBO, even though it was well-designed. The 2011 evidence, as mentioned before, is a study by Annane in Intensive Care Medicine. This is the more recent study showing no benefit. However, if you thought the Weaver study had flaws, this one is even worse. They enrolled patients between 1989 and 2000 – but didn’t publish until 2011, which is a massive red flag. Their endpoint is fuzzier, as they simply have a questionnaire and a physical examination as their follow-up without a lot of details. But, for what it’s worth, they found HBO was futile in non-comatose patients and harmful in comatose patients. They also do not dive as low or as long as the patients in the Weaver study.
Each of these studies makes it in the Cochrane Review which finds a cumulative nonsignificant trend towards minimal improvement in the HBO group. The problem is, HBO therapy is expensive, causes hyperoxic seizures, barotrauma, anxiety, oxidative stress and both hyperthermia and hypothermia. Weak evidence for mild improvement in delayed neurologic sequelae at 6 weeks is not a strong enough motivator for me to be enthusiastic about subjecting someone to the risks of HBO therapy. I’d love to see more data.
“Hyperbaric Oxygen for Acute Carbon Monoxide Poisoning.”
www.ncbi.nlm.nih.gov/pubmed/12362006
“Hyperbaric Therapy for Acute Domestic Carbon Monoxide Poisoning: Two Randomized Controlled Trials.”
www.ncbi.nlm.nih.gov/pubmed/21125215
“Hyperbaric Oxygen for Carbon Monoxide Poisoning (Review).”
www.ncbi.nlm.nih.gov/pubmed/21491385
The Mortality Burden of Homelessness
Anyone working in the Emergency Department knows that homelessness and psychiatric disorders go hand-in-hand – and that also goes psychiatric disorders and substance abuse. This study confirms what we already know about the prevalence of these issues in the homeless population.
The most interesting number I read out of it was that the life expectancy of a homeless male aged 15-24 years was 38.7, and 47.4 for similarly aged homeless females – compared to life expectancies of 60.3 and 64.8 in their general population. It makes me wonder how much of that life expectancy difference is just the homelessness, or whether it’s the psychiatric and substance abuse disorders – I would probably say most of that difference is made up with the substance abuse.
“Psychiatric disorders and mortality among people in homeless shelters in Denmark: a nationwide register-based cohort study.”
http://www.ncbi.nlm.nih.gov/pubmed/21676456
“Teachable Moments”
From the critical care literature, looking at whether the ICU admission represents a “teachable moment” for counseling against health-endangering behaviors. It’s a review article asking the question whether interventions at the time of admission to an ICU – i.e., a close brush with death – are effective.
This is relevant to the Emergency Department for those situations where you want to shake your patients and tell them “you did this to yourself, you fool!”
They look at the literature for nicotine cessation and for alcohol cessation. The nicotine cessation literature is rather bleak. They break down the interventions to <15 minutes vs. >15 minutes, and then whether contact after hospital discharge is helpful. Pretty much, unless you have a mechanism for prolonged after-discharge contact and counseling, you won’t get any meaningful results.
As far as alcohol goes – there are good studies that support questionnaires, lab work, or scoring systems to identify individuals at risk for alcohol-related injuries or illness. However, all the studies in their review show regardless of behavioral intervention, no decrease in alcohol consumption at discharge is seen.
So, sadly, almost assuredly, the ED, with the minimal time and follow-up available to us, is unlikely to be a place where impactful counseling is feasible.