Emergency Medicine Literature of Note

Linezolid Is Superior To Vancomycin For Pneumonia

This is consistent with prior studies and not particularly earthshaking, but if you needed more literature to support switching antibiotics in the case of treatment failure, this would be another one.

This is in pigs, and it’s an animal model of MRSA ventilator-associated pneumonia. Four groups – controls, twice-daily vancomycin, continuous vancomycin infusion, and linezolid. Treatment was initiated after 12 hours of bacterial inoculation in ventilated pigs. At the end of their 96 hour treatment period, 75% of controls, 11% of each vancomycin group, and 0% of linezolid pigs were BAL positive for MRSA by culture. Likewise, pathologic sections also showed decrease inflammation and damage in the linezolid group.

Short story, linezolid is better – but not quite better enough that we can’t still start with vancomycin and keep it in reserve.

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”

www.ncbi.nlm.nih.gov/pubmed/21878099

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

Featured on ERCast

Was fortunate enough to be invited to appear on one of the premier Emergency Medicine podcasts – ERCast, by Dr. Rob Orman (@emergencypdx).

We had a lovely chat about two posts from August, clearance of C-spine by CT vs. MRI (link) and CT within 6 hours for the diagnosis of SAH (link). The esteemed Dr. Scott Weingart of EMCrit also weighs in on the CT article.

He’s been podcasting far longer than I’ve been writing, and he has a lot of fantastic content and has been featured on EM:RAP as well. If you haven’t discovered it yet, you’re missing out.

Back Pain, Harbinger of Death

In Perth, Western Australia, clearly back pain is a different sort of entity than back pain here in the United States. This is a retrospective review of 22,000 back pain representing 1.9% of all visits over a five year period simply as an epidemiologic overview with descriptive statistics.

And, fascinating statistics they are. Highlights:
– 43.8% of patients were diagnosed with simple muscular back pain.
– 17.1% of muscular back pain patients required admission to the hospital with a mean length-of-stay of 6.4 days, and one that was hospitalized for 163 days!
– Patients at the extremes of age (< 15 years, > 75 years) were simple muscular back pain less than 40% of the time.
– Of the medical diseases found in the non-muscular group, the top were renal colic, sciatica, UTI/pyelonephritis.
– 24 myocardial infarctions, 53 pulmonary emboli, 17 aortic dissections, and 18 ruptured AAA were diagnosed in patients with a primary complaint of back pain.

How do 17.1% of simple muscular back pain patients get admitted to the hospital? For six days? It boggles the mind.

Finally – back pain at the harbinger of death – there was a 1.2% 30-day mortality rate in all patients presenting for any complaint of back pain, and 0.8% with non-specific or muscular back pain. That’s almost as lethal as our low-risk chest pain cohort here in the U.S.

Fascinating.

“Analysis of 22,655 presentations with back pain to Perth emergency departments over five years”
www.ncbi.nlm.nih.gov/pubmed/21923920

No Reversing The Harm of Etomidate

A small, but growing body of evidence is starting to correlate the physiologic adrenal suppression of etomidate with worsening clinical outcomes. This study is a French prospective cohort that really likes etomidate for RSI, so, they decided to ask the question whether a continuous hydrocortisone infusion has any substantial effect on cardiovascular parameters in the setting of etomidate use.

Short answer, no.

Their randomized groups are awfully small – 45 patients in each group – so their power to detect a difference is not great. But, at the minimum, there’s no profoundly obvious difference or any seemingly clinically significant trend between the two groups.

I trained using etomidate for everyone, but I’ve almost completely moved to alternative agents, ketamine being the most prominent of those agents. Most significantly, ketamine differs from the other agents in terms of having analgesic properties as well, and I think it is reasonable to provide some treatment for the pain associated with laryngoscopy. There is evidence that ketamine is a myocardial depressant and may be deleterious in patients with limited cardiac reserve, but so far in limited literature it holds up clinically well against etomidate and midazolam.

“Corticosteroid after etomidate in critically ill patients: A randomized controlled trial”
http://www.ncbi.nlm.nih.gov/pubmed/21926601

“Intubating ICU patients with ketamine: adverse effects that can occur.”
http://www.ncbi.nlm.nih.gov/pubmed/18079246

Blocking Frizzled Proteins Reduces Infarct Size

This is another window-to-the-future article that caught my eye because, really, I just wanted to see what a Frizzled signal was.

And, it turns out, it’s mildly interesting.

My area of expertise is not cell signaling and infarct-related myocardial fibroblast migration/inhibition, so the first few pages of cell plating and luciferase expression measurement are not my cup of tea. However, eventually, the authors get around to injecting UM206 into a mouse MI model and find significant reductions in infarct size, increased myofibroblasts, and, more importantly, increased ejection fraction/decreased mortality from heart failure.

Give it another five years, and maybe we’ll be giving our ACS patients aspirin, clopidogrel, and a Frizzled-antagonist.

“Blocking of Frizzled Signaling With a Homologous Peptide Fragment of Wnt3a/Wnt5a Reduces Infarct Expansion and Prevents the Development of Heart Failure After Myocardial Infarction.”
circ.ahajournals.org/content/…/CIRCULATIONAHA.110.976969.abstract

MRI After Negative CT in Obtunded Trauma

In contrast to the recently reviewed study showing 5 surgical injuries in 174 patients complaining of neck pain after a negative CT c-spine, this study of MRI in obtunded trauma patients with a negative CT c-spine showed no surgical injuries.

Specifically, this is a retrospective review from U.C. Davis in which they looked at 512 patients who underwent both CT c-spine and MRI c-spine. They found 150 patients who were confused/obtunded, had otherwise normal neurologic examination, and had a negative initial CT c-spine. Half of these patients had an injury identified on their MRI, but none of them were unstable ligamentous injuries or structural abnormalities requiring surgical intervention.

This is more relevant to our trauma colleagues who need to mobilize people in the ICU to prevent other complications, and external validity is limited in a single-center study, but it’s a mark on the side of keeping the standard of care at CT and not proceeding to MRI in an irrational manner.

“The Value of Cervical Magnetic Resonance Imaging in the Evaluation of the Obtunded or Comatose Patient With Cervical Trauma, No Other Abnormal Neurologic Findings, and a Normal Cervical Computed Tomography.”
www.ncbi.nlm.nih.gov/pubmed/21857257

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

We’re Covered in Filth

This is not the first study showing physician white coats and nursing uniforms are colonized with bacteria, nor that may of those bacteria are pathogenic and multi-drug resistant. In the past, this has been used as a call for the abolishment of physician white coats, ties, and all long-sleeved apparel.

This study, however, shows that short-sleeved nursing uniforms were just as likely to be coated with bacteria – 49% to 54%. Interestingly, even “changing uniform daily” still resulted in colonization with pathogenic bacteria. The authors speculate the main issues are that all textiles easily transmit bacteria, and that hand hygiene might be more critical than uniforms in prevent transmission from patients to physician clothing.

This study also, like the many before it, doesn’t demonstrate anything but colonization – not documented patient-to-patient transmission via healthcare worker clothing or any specific outcome measures. However, I am a believer that white coats are fomites and medical relics that should go the way of bloodletting and golden elixirs. The studies in support of white coats cite patient satisfaction and ease of identification of roles – which, while important, could be mitigated by new interventions for identification of healthcare providers. Even though we yet have no evidence of harms from this colonization with pathogenic bacteria, it’s essentially a zero-cost intervention to stop wearing white coats and ties – so even if the number needed to treat to prevent a transmissible infection is immense, it’s a free way to protect our patients as best we can.

“Nursing and Physician Attire as Possible Source of Nosocomial Infections.”
www.ncbi.nlm.nih.gov/pubmed/21864762