Articles of the year (EMU 2018)

Hand out for the articles of the year lecture at EMU 2018

I love evidence based medicine, but I definitely understand the criticism that EBM nerds like myself can come across as very negative. Thrombolytics don’t work. BNP isn’t helpful. Stress testing is a sham. Idarucizumab? Yeah right. I think this scientific criticism is crucial, but I understand that it isn’t always fun. So when I was asked to present my favourite articles of the year at the North York General Emergency Medicine Update, I decided to stay entirely positive. I only chose papers that were potentially  practice changing, but more importantly, that could have a positive impact on clinical practice. These are the papers I chose.

Inhaled isopropyl alcohol for nausea and vomiting

April MD, Oliver JJ, Davis WT et al. Aromatherapy Versus Oral Ondansetron for Antiemetic Therapy Among Adult Emergency Department Patients: A Randomized Controlled Trial. Annals of Emergency Medicine. 2018. PMID: 29463461

Methods:

  • A single-center, randomized, placebo-controlled, 3 group trial of a convenience sample of 120 adult patients presenting to the emergency department with a chief complaint including nausea or vomiting.
  • They excluded patients with an IV already in place, but patients had to have a nausea score of at least 3/10 to get into the trial.
  • There were 3 groups:
    • Inhaled isopropyl alcohol and 4mg oral ondansetron
    • Inhaled isopropyl alcohol and oral placebo
    • Inhaled placebo and 4mg oral ondansetron
  • The primary outcome was nausea at 30 minutes.

Results:

  • At the start of the trial, the 3 groups all rated their nausea as about 50/100
  • The 30 minute reduction in nausea were:
    • Isopropyl + placebo = 32/100
    • Isopropyl + ondansetron = 30/100
    • Placebo + ondansetron= 9/100
  • Both groups with inhaled isopropyl alcohol were statistically improved as compared to placebo. Ondansetron didn’t seem to have any effect over placebo.
  • The isopropyl alcohol groups also had less nausea at the time of disposition, less pain at 30 minutes, less use of rescue antiemetics, and higher satisfaction scores.

Caveats:

  • This is a single center study and they did not capture consecutive patients.
  • Blinding is not ideal. Although they obscured the packaging, isopropyl alcohol has a distinct odor as compared to saline, and patients were able to identify in by smell. That being said, the isopropyl alcohol group only correctly identified their group 53% of the time. Something seems fishy about the numbers though, because when asked to identify the oral medication, only 10% of people guess the correct group in what should be a better than 50/50 guess.
  • The trial is too small to provide us adequate information about harms.
  • By excluding patients with IVs in place, this was a milder group of patients than we usually see in the ED.
  • 30 minutes may not be the best primary outcome. When I am nauseated, I absolutely want something that makes me feel better right away, but when managing ED patients I also need something that works longer to allow for effective discharge and outpatient management.
  • I am not sure how quickly ondansetron is supposed to work. We know it helps our sicker pediatric gastro patients. Maybe 30 minutes was too early to see an ondansetron effect?
  • A similar RCT was covered in the December articles of the month.

Why I chose this paper:

  • This is a simple, low cost intervention that looks like it will help relieve one of the worst symptoms we encounter.

My bottom line:

  • Although I would like to see larger trials to confirm the effect and clarify the possible harms, I will start using inhaled isopropyl alcohol to help treat nausea now.

Other FOAMed commentaries:

 

Haldol for Gastroparesis

Roldan CJ, Chambers KA, Paniagua L, Patel S, Cardenas-Turanzas M, Chathampally Y. Randomized Controlled Double-blind Trial Comparing Haloperidol Combined With Conventional Therapy to Conventional Therapy Alone in Patients With Symptomatic Gastroparesis. Academic emergency medicine. 2017. PMID: 28646590 [full text]

Methods:

  • A randomized, double-blind placebo-controlled trial.
  • They included 33 adult patients presenting to the emergency department with abdominal pain due to their known gastroparesis.
  • They compared haloperidol 5 mg IM to placebo. Patients all got conventional therapy at the discretion of the treating physician.
  • They excluded patients with a past history or current evidence of QT prolongation, hypotension (systolic blood pressure < 90 mm Hg), presence of other acute abdominal pathologic conditions, allergy to haloperidol, pregnancy, incarcerated status, or an inability to give informed consent.
  • The primary outcomes were pain and nausea at 1 hour.

Results:

  • Pain was improved with haloperidol. Pain decreased from a mean of 8.5 to 3.1 with haloperidol (p<0.001). It decreased from a mean of 8.3 to 7.2 with placebo (p=0.11).
  • Nausea was also improved with haloperidol. It decreased from a mean of 4.5 to 1.8 with haloperidol (p<0.001), but only decreased from a mean of 4.1 to 3.4 with placebo (p=0.05)
  • Fewer patients were admitted in the haloperidol group (27% vs 72%).
  • ED length of stay was statistically unchanged, but the point estimate favoured haloperidol (5 vs 9 hours, p=0.77).
  • There were no adverse events reported.

Caveats:

  • This is a small trial and because of slow recruitment they did not reach their intended sample size.
  • The authors decided to only include patients with a known diagnosis of gastroparesis, but we see many more patients with undifferentiated vomiting syndromes in the emergency department.
  • Trials should really only have a single primary outcome, while this trial had two.
  • Small trials can result in false negative results. A 4 hour difference in ED length of stay is certainly clinically important, but the small numbers here mean that we cannot not make definitive conclusions about length of stay.
  • There were some baseline imbalances between the groups in terms of other treatments used (such as morphine and ondansetron) that could be confounders in this small study.
  • This trial is far too small to make any conclusions about adverse events or the safety of this approach.

Why I chose this paper:

  • Patients with recurrent vomiting symptoms can be very challenging to manage and this paper describe a management option that can relieve their symptoms and help us discharge them home.

My bottom line:

  • I have been using haloperidol for cyclic vomiting for a few years. Until someone brings droperidol back to Canada, haloperidol will remain a key component of my cyclic vomiting management strategy.

Other FOAMed commentaries:

Bonus trial: Ramirez R, Stalcup P, Croft B, Darracq MA. Haloperidol undermining gastroparesis symptoms (HUGS) in the emergency department. The American journal of emergency medicine. 2017; 35(8):1118-1120. PMID: 28320545

This was a second article on the same topic last year. It was a chart review that identified 52 adult patients with diabetic gastroparesis who had been treated with haloperidol (5 mg IM). As a control, they looked at the patients’ most recent visit for nausea and vomiting in which they weren’t given haloperidol. When given haloperidol, patients were admitted to the hospital less often (10% vs 27%, p = 0.02) and required less pain medication (median 6.75 vs 10.75 morphine equivalents, p=0.009). There was no difference in ED length of stay or hospital length of stay if admitted. There were no episodes of dystonia, akasthesia, excessive sedation, or cardiovascular complications.

 

Flush rate oxygen for preoxygenation

Driver BE et al. Flush Rate Oxygen for Emergency Airway Preoxygenation. Annals of emergency medicine. 2017; 69(1):1-6. PMID: 27522310

Methods:

  • This is a cross-over, non-inferiority study in 26 healthy volunteers.
  • They looked at 4 different pre-oxygenation strategies: a nonrebreather mask at 15 L/min, a non-rebreather mask at flush rate (probably about 50 L/min by turning the flow meter as far as it will go), a BVM at 15 L/min, and a standard face mask at flush rate. All techniques were done for 3 minutes.
  • The primary outcome was the fraction of expired oxygen.

Results:

  • The mean FeO2 numbers were:
    • Nonrebreather at 15L/min: 54% (95% confidence interval [CI] 50% to 57%)
    • Nonrebreather at flush rate: 86% (95% CI 84% to 88%)
    • BVM with a proper 1 way valve: 77% (95% CI 74% to 81%)
    • Face mask: 72% (95% CI 69% to 76%)
  • The non rebreather at flush rate was statistically superior to the nonrebreather at 15 L/min (as well as the facemask). It was non-inferior to the BVM technique.

Caveats:

  • When I am pre-oxygenating, my goal is to fill the lungs with oxygen. Therefore, the outcome of FeO2 makes sense, and is something I care about. However, it is not a patient oriented outcome. I would still like to see this confirmed in a study looking at patient oriented outcomes in the peri-intubation period.
  • They were looking at healthy volunteers here. Sicker patient will often have much higher minute ventilations and shunt physiology that makes maintaining oxygenation more difficult. These results might not extrapolate well to our critically ill patients.
  • This is a single center, unblinded trial.
  • Ideal BVM pre-oxygenation requires a perfect mask seal. It isn’t clear how good a seal was achieved in this study, and leaks would make the numbers worse. That being said, a BVM seal is probably easier to achieve in healthy, co-operative volunteers than in critically ill, dyspneic patients.
  • There are very few harms here, but if you work in a setting with limited oxygen supply (EMS) this technique will quickly deplete your supplies, and so should not be used.
  • In most places, BVMs do no come with an appropriate one way valve attached, and so the patient can breath room air if they are spontaneously breathing. This trial used a one way valve. The results here are therefore probably better than what would be seen with BVMs used in routine practice. This is explained further in this post.

Why I chose this paper:

  • Filling the lungs with oxygen before an intubation attempt gives us a buffer, hopefully providing adequate time for intubation and increasing patient safety. The way I was taught pre-oxygenation was to use a non-rebreather at 15 L/min for 4 minutes or 8 vital capacity breaths. This standard technique doesn’t come anywhere close to filling the lungs with oxygen. The BVM technique would be fine, but is more technically difficult are requires someone to maintain a perfect mask seal throughout the pre-oxygenation period. The simple technique of turning the oxygen flow all the way up looks like it could help patients and give us a better safety buffer when intubating.

My bottom line:

Other FOAMed commentaries:

 

Post contrast acute kidney injury

Aycock RD, Westafer LM, Boxen JL, Majlesi N, Schoenfeld EM, Bannuru RR. Acute Kidney Injury After Computed Tomography: A Meta-analysis. Annals of emergency medicine. 2018; 71(1):44-53.e4. PMID: 28811122

Methods:

  • This is a systematic review and meta-analysis.
  • They included 28 studies (107,335 patients) assessing renal insufficiency after contrast enhanced CT.
  • The studies had to have both a contrast and a non-contrast group. They did not look at use of contrast for intra-arterial procedures, pediatrics, or prevention strategies.
  • The primary outcome was the rate of acute kidney injury in the group receiving a contrast enhanced CT as compared to patients who did not receive contrast.

Results:

  • Contrast was not associated with acute kidney injury (OR 0.94; 95%CI 0.83-1.07).
  • Contrast was also not associated with need for dialysis (OR 0.83) or mortality (OR 1.0).
  • In the 6 studies that used propensity matching techniques, contrast was not associated with nephropathy (​OR 0.98, 95% CI 0.92-1.05).

Caveats:

  • A systematic review is only as good as the studies it includes. All of the included studies are observational. There are a huge number of confounders that could impacts these results. There are no RCTs on this topic.

Why I chose this paper:

  • In critically ill patients, determining the correct diagnosis quickly is essential. The practice of delaying contrast scans until a patient’s renal function is known is inefficient and can be risky in sick patients. We need to be comfortable ordering the right test at the right time in critically ill patients without being distracted by rare or potentially non-existent harms.

My bottom line:

  • This data cannot prove that contrast is perfectly safe. However, it does illustrate that the risk from contrast, if it really exists, is small enough that it should not prevent use of contrast when necessary in emergency department patients.

Other FOAMed commentaries:

 

Femoral nerve blocks for hip fractures

Unneby A, Svensson O, Gustafson Y, Olofsson B. Femoral nerve block in a representative sample of elderly people with hip fracture: A randomised controlled trial. Injury. 2017; 48(7):1542-1549. PMID: 28501287 [free full text]

Methods:

  • This is a randomized, controlled trial.
  • They included 266 patients 70 years or older with verified hip fractures on an orthopaedic ward.
  • Patients were randomized to receiving a femoral nerve block with additional opioids as required or no nerve block with just opioids for pain control.
  • The nerve block here was done with a nerve stimulator. They injected a total of 40 ml of 0.25% levobubivacaine.

Results:

  • Pain scores were low at baseline. There was a statistically significant reduction in pain score in the nerve block group between 2 and 12 hours, although based on the median pain scores reported, it is hard to determine how many patients had a clinically meaningful response.
  • 83% of the control group required IV opioids as compared to only 40% of the nerve block group.
  • There were no adverse events.

Caveats:

  • This study took place on an orthopaedic ward and the blocks were done by anesthesiologist. However, hip fracture patients on the ward are the same patients I see in the emergency department, and this is an easy procedure that is easily performed by emergency physicians.
  • Nerve stimulators are not commonly used in emergency departments, but point of care ultrasound also allows immediate verification of needle position.
  • Pain was assessed at rest, but most hip fracture patients are relatively pain free when not moving. The value of the nerve block is evident when patients need to be moved.
  • It is hard to improve pain a lot when the starting pain score is a median of 3/10.
  • They included all patients, including patients with significant dementia. Obviously, pain scores can be difficult to assess in patients who are not communicative due to their dementia. They use a proxy to help with those patients, but it does muddy the waters a little bit.
  • Pain assessments were not done by research personnel, but rather by clinical nurses, who obviously have a lot of other important duties. Consequently, many patients were missing pain assessments at various time points.
  • The study is not large enough to fully assess possible adverse events.

Why I chose this paper:

  • This is by no means a perfect paper, but fits with other studies on the subject. (Fletcher 2003; McRae 2015) This is a procedure that is easily within the scope of practice for emergency physicians and seems to make a big difference in the comfort level of some patients while they await surgery. We rarely have perfect evidence in medicine. We should continue to demand better evidence for all our practices, but in the meantime we have to treat patients. Nerve blocks are relatively safe and have an obvious significant upside, so the current evidence is enough to convince me to offer this to all of my patients.

My bottom line:

  • I offer an ultrasound guided hip block to all of my patients with hip fractures.

Other FOAMed commentaries:

 

Needle aspiration for pneumothorax

Thelle A et al. Randomised comparison of needle aspiration and chest tube drainage in spontaneous pneumothorax. The European respiratory journal. 2017; 49(4). PMID: 28404647

Methods:

  • Multicenter, randomized, controlled trial looking at 127 adult patients with spontaneous pneumothorax requiring intervention (at least 30% or patient feeling significantly short of breath).
  • Randomized to either needle aspiration or a chest tube connected to suction.
  • The primary outcome was length of hospital stay.

Results:

  • Hospital length of stay was shorter in the needle aspiration group, but the length of stay in both groups was much much longer than the hours I am used to (2.4 vs 4.6 days).
  • About 50% of the aspirations were successful on the first attempt. When unsuccessful, a second attempt was made, and about 50% of those were successful.
  • There were no complications in the aspiration group compared to 15 with the chest tube (4 wound infections, 2 bleeds, 7 subcutaneous emphysema, 1 pneumonia, and 1 empyema).

Caveats:

  • The system here is clearly different than in Canada, as all my spontaneous pneumothorax patients are headed home in an hour or two. However, when I place a chest tube it remains in place for 2-3 days, and patients seem to appreciate the opportunity to go home without plastic tubing sticking out of there chests.
  • The study is unblinded, and decisions about length of stay are subjective.
  • The adverse events are concerning, but the numbers are small, making definitive conclusions difficult.
  • They don’t look at other patient important outcomes, like pain or satisfaction.
  • There are other papers that come to similar conclusions. (Ayed 2006; Parlak 2012; Korczynski 2015)

Why I chose this paper:

  • Chest tubes are not comfortable. I think less invasive options will be greatly appreciated by our patients.

My bottom line:

  • I think needle aspiration is a great idea. I seem to have about the same success rate as these researchers (50%). Honestly, though, I now treat almost all pneumothoraces conservatively, with a wait and see approach, which seems to make patients even happier.

Other FOAMed commentaries:

 

Non-rigid immobilization of buckle fractures

Jiang N, Cao ZH, Ma YF, Lin Z, Yu B. Management of Pediatric Forearm Torus Fractures: A Systematic Review and Meta-Analysis. Pediatric emergency care. 2016; 32(11):773-778. PMID: 26555307

Methods:

  • A systematic review looking at 8 randomized controlled trials with 781 total pediatric patients with torus (buckle) fractures of the forearm and comparing a rigid cast to any non-rigid method of immobilization.

Results:

  • Because different trials looked at different outcomes (heterogeneity) the results are descriptive, rather than combined into a meta-analysis.
  • Functional outcomes were better with non-rigid group: more range of motion, earlier return to normal activity, and less difficulty with bathing.
  • 3 studies specifically looked at complications, and all 3 demonstrated increased complications in the rigid immobilization group. (About 25% vs 7% overall).
  • If given the choice, parents prefer the option that can be removed for bathing.

Caveats:

  • Different studies used different forms of non-rigid immobilization, from velcro splints to just tensor bandages. It would be nice to know if there are differences in outcomes among these different options.
  • The quality of the underlying studies is only moderate. None of the trials were blinded, which can result in bias.
  • There was a large variance in the reported rate of complications from casting, making the actual numbers questionable. Different studies may have been using different definitions, or some studies simply might not have been looking for complications.

Why I chose this paper:

  • Traditional plaster splints are inconvenient, to say the least. I would favour a removable splint even if the outcomes were identical. The fact that outcomes actually favour the removable splint is a strong argument to abandon plaster in these children.

My bottom line:

  • A removable velcro splint is my go to for forearm buckle fractures.

I chose these articles because I think they all represent potentially positive practice changes for our patients. No article is perfect. I always recommend reading papers for yourself, applying your own expertise, and making your own decisions. If you are not comfortable reading papers, make sure to check out the post “EBM is easy“.

Cite this article as: Justin Morgenstern, "Articles of the year (EMU 2018)", First10EM blog, April 25, 2018. Available at: https://first10em.com/articles-of-the-year-emu-2018/.

Author: Justin Morgenstern

Emergency doctor working in the community. FOAM enthusiast. Evidence based medicine junkie. “One special advantage of the skeptical attitude of mind is that a man is never vexed to find that after all he has been in the wrong.” - William Osler

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