The best articles I found this year

A ‘best of’ list? What gives? It’s March. Didn’t these get played out back in January? Although the world may have turned a year older on January 1st, I prefer March 4th – the day First10EM turned 1. As a nerdy celebration, I went through all the papers I covered in the Articles of the Month and came up with favorite EBM topics of the year:

#10: Droperidol is not evil

I have never prescribed droperidol. It has never even been available to me. I have read about it, though. I’ve seen studies that show it is better for migraines, better for sedation, and better for nausea than the drugs we we are currently using. However, I always ignored those studies, because everyone knows droperidol is unsafe. Whatever benefits it has, they are clearly outweighed by the harm emphasized by its black box. (Although, the circumstances that led to that black box were suspicious, to say the least.) It turns out, droperidol is probably as safe as any of the antipsychotics that we use. I want it back. We should all want it back. For our own safety, and for the good of our patients, it’s time to demand droperidol be returned to formularies everywhere.

The papers reviewed this year:

Calver L, Page CB, Downes MA, et al. The Safety and Effectiveness of Droperidol for Sedation of Acute Behavioral Disturbance in the Emergency Department. Ann Emerg Med. 2015. PMID: 25890395

This is a prospective observational study of 1009 patients in Australia, all of whom received 10mg of droperidol for sedation of acute behavioral disturbances, and second dose at 15 min as needed. Out of those 1009 patients, 13 developed a long QT, and 7 of those had other contributing causes such as methadone or amiodarone. There were no incidences of torsades de pointes. Bottom line: The black box warning against droperidol is likely without scientific merit. I would use it if it were available to me. Given how useful this medication is, it might be worth fighting for.

Calver L, Isbister GK. High dose droperidol and QT prolongation: analysis of continuous 12-lead recordings. Br J Clin Pharmacol. 2014;77:(5)880-6. PMID: 24168079

I included the much larger study by the same group last month, but it is always nice to explore how many high level decisions in medicine lack a scientific basis. In this prospective observation study, they gave 46 psychiatric patients between 10 and 25 mg of IV droperidol for sedation. All were placed on holter monitors. There were no dysrhythmias. Only 4 patients had any lengthening of their QT and all 4 had other reasons for this, such as methadone. Bottom line: We should not give up excellent medications based on shoddy science.

#9: Age adjusted D-dimer

We’ve been hearing about it for a while, but I think 2015 was the tipping point for age adjusted D-dimer. There are still some debates; there is not a standard assay; but I think there is now enough data to support using this in clinical practice. I do (although I rarely order a D-dimer) and I love it.

Papers review:

Righini M et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. JAMA 2014;311(11):1117-1124. PMID: 24643601

This is a prospective observational study of 3346 patients with suspected PE (the total rule in rate was 19%), of which a total of 331 had D-dimers greater than 500, but less than age x 10. Using the adjusted D-dimer level of age x 10, they would have missed 1 PE out of 331 patients (0.3%). Unfortunately, not everyone got the gold standard test (CTPA), so it is possible they missed a few more that we don’t know about. However, if the test threshold for PE generally is 2%, and the elderly are particularly prone to renal problems from CT contrast, avoiding 331 CTPAs at the cost of one missed diagnoses might be worth it. The other major problem is that D-dimers are not standardized and there are multiple different assays. Bottom line: If the D-dimer is less than age x 10, the risk is probably low enough to stop further testing. I use this to (and this is crazy, I know) talk to my patients about whether or not to scan.

Jaconelli Y and Crane S. Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 2: Should we use an age adjusted D-dimer threshold in managing low risk patients with suspected pulmonary embolism? Emerg Med J 2015;32(4):335-7. PMID: 25804861

This is a systematic review (published before last month’s paper, and so not including it) that found 13 papers addressing the use of an age adjusted d-dimer (less than age x 10). Most of the studies were retrospective, so not of high quality. The authors conclusion is “In older patients suspected of having a PE, with a low pretest possibility, an age-adjusted D-dimer increases specificity with minimal change in the sensitivity, thereby increasing the number of patients who can be safely discharged without further investigations.” Bottom line: It is looking like the age adjusted d-dimer in low pre-test probability patients will result in a post-test probability below the test threshold, while increasing specificity.

#8 NPO time is irrelevant for procedural sedation

This publication had an immediate impact on my practice. Admittedly, many of us were already bending the rules around NPO times, but an official clinical policy from ACEP that told us not to delay procedural sedation based on fasting time was amazing. I have printed this paper more than any other since I started writing the Articles of the Month.

Paper reviewed:

Godwin SA et al. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2014;63(2):247-58. PMID: 24438649

As part of the ACEP clinical policy process, they did a systematic review. They found 5 studies that cover thousands of patients, and found no evidence that fasting decreased aspiration or other adverse events. The official policy is “Level B: Do not delay procedural sedation in adults or pediatrics in the ED based on fasting time. Preprocedural fasting for any duration has not demonstrated a reduction in the risk of emesis or aspiration when administering procedural sedation and analgesia.” Bottom line: Just make sure they actually take the Doritos out of their mouth before starting.

#7: Medical expulsive therapy for kidney stones is out

Why would this make the list? It’s not exciting. It’s not particularly helpful. Avoiding medications is always good, but tamsulosin isn’t even that harmful or expensive. This seems like a topic to skip, but it makes the list because I love being proven wrong. In residency, I was an early adopter of tamsulosin based on the systematic reviews that came out at the time. Now we have far better clinical trials and I no longer prescribe this drug. I was wrong; I changed my practice. That is the essence of good science and good medicine. This makes the list, not because the topic is necessarily groundbreaking, but because it is a good reminder that we are all wrong about a lot of things. If you don’t think you’ve been wrong recently, you might want to look harder.

Papers reviewed:

Pickard R et al. Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial. Lancet. 2015. PMID: 25998582

Flomax was pushed for renal stones based on a number a small studies with horrible methods and a few meta-analyses of those horrible studies. There has already been one large RCT with excellent methods demonstrating that Flomax doesn’t work. This should be the nail in the coffin. This is a multicentre placebo controlled RCT of 1167 adult patients with CT confirmed renal stones. They were randomized to either tamsulosin 0.4mg, nifedipine 30mg, or placebo. There was no difference between any of the groups in the number of patients requiring urologic intervention. (About 80% of the patients passed spontaneously, and 20% required an intervention in all groups.) Bottom line: There is no role for medical expulsive therapy in renal colic.

Furyk JS, Chu K, Banks C, et al. Distal Ureteric Stones and Tamsulosin: A Double-Blind, Placebo-Controlled, Randomized, Multicenter Trial. Ann Emerg Med. 2015. PMID: 26194935 [free full text]

This is a prospective, randomized, double-blind trial of 403 adults with CT confirmed ureteric stones comparing tamsulosin 0.4mg daily to placebo. There was no benefit for the primary outcome of stone expulsion at 28 days, with 87% passed in the tamsulosin group and 81.9% in the placebo group (5.1% difference; 95%CI -3 to 13%). There was a difference in a secondary outcome, distal stones sized 5-10mm, with 83.3% passing as compared to 61%. Of course this is a secondary outcome, so should not affect your practice. More importantly, the vast majority of these people should not being getting imaged, so you will never know the size of the stone, making this information clinically useless. There was no difference in urologic interventions, pain, or analgesia requirements. Bottom line: Tamsulosin doesn’t help patients with ureteric stones.

Berger D, Ross M, et al. Tamsulosin does not increase one-week passage rate of ureteral stones in Emergency Department patients. Am J Emerg Med. 2015. In Print. PMID:

This is yet another paper indicating tamsulosin has no role in ureterolithiasis. (Its too bad we can’t just start with the high quality studies, rather than following the predictable pattern of a handful of garbage studies showing questionable benefit followed by a lot of time and money spent on multiple good trials that prove that there was never any benefit.) This was a prospective, double-blind RCT with 127 adult patients with CT confirmed ureterolithiasis, randomized to either tamsulosin 0.4mg daily or placebo. There was no difference in the number of patients in whom the stone did not pass (tamsulosin 62.1% 95CI 49-75%; placebo 54.4% 95%CI 40-67%.) There was also no difference in pain scores or analgesic use. Bottom line: There is no reason to be using tamsulosin in renal colic patients.

#7B: Sex for kidney stones

Honestly, the whole reason for this post is to bring this paper up again. I don’t get to write about sexy topics too often on First10EM. This deserves at least a second look. How many of you have had this conversation with your patients? This might be my favorite article of the year, but like all new treatments, be sure to use it now before it stops working in future trials.

The paper:

Doluoglu OG, Demirbas A, Kilinc MF. Can Sexual Intercourse Be an Alternative Therapy for Distal Ureteral Stones? A Prospective, Randomized, Controlled Study. Urology. 86(1):19-24. 2015. PMID: 26142575

By now, everyone should know that tamsulosin does not help patients with kidney stones, but that doesn’t mean we should give up on our patients. Is there anything else we can do to help? In this randomized, controlled study 75 adult patients with nephrolithiasis were randomized to either 1) being asked to have sex at least 3-4 times a week, 2) tamsulosin 0.4mg a day, or 3) usual care. There were no placebos (although if you can come up with a placebo version of sex I want to hear about it.) The mean time to stone expulsion was only 10 days (95%CI 4.2-15.8 days) in the sex group, versus 16.6 (95%CI 8.1-25.1 days) with tamsulosin and 18 (95%CI 15.5-23.5 days) with usual care (p=0.0001). I foresee a large number of men looking for medical notes explaining this therapy to their partners. Perhaps there may even be a few malingerers without stones looking to get this prescription? Bottom line: Sex is good

#6: It’s OK to start vasopressors peripherally

I was doing this anyway. In the community, there often isn’t any other option. However, having some evidence to support an early focus on resuscitation and delaying central lines until you are calm and properly sterile conditions can be achieved is fantastic.

Loubani OM, Green RS. A systematic review of extravasation and local tissue injury from administration of vasopressors through peripheral intravenous catheters and central venous catheters. J Crit Care. 2015;30:(3)653.e9-17. PMID: 25669592

This systematic review looked for any primary studies or case reports that described local tissue injury from vasopressor extravasation, and includes 85 articles and 270 patients. Although there are reports of tissue injuries after peripheral vasopressor administration, these tend to occur after very long use (the average duration of infusion was 55.9 hours.) Bottom line: Although data is pretty limited, I would be very comfortable starting vasopressors through a peripheral line. Long term management should probably include central access.

#5: A brilliant, simple innovation for pediatric resuscitation

This may have only been simulation research. It may not have provoked widespread practice change (yet). But these colour-coded syringes are brilliant. Cognitive offloading the dose calculations in the most stressful possible resuscitations just makes sense. I hope I can get these reproduced for my shop.

Moreira ME, Hernandez C, Stevens AD, et al. Color-Coded Prefilled Medication Syringes Decrease Time to Delivery and Dosing Error in Simulated Emergency Department Pediatric Resuscitations. Ann Emerg Med. 2015;66:(2)97-106.e3. PMID:25701295

Pediatric resuscitations are stressful at the best of times and pediatric medication doses can be complicated, increasing the risk of medication errors. This group came up with an ingenious solution: single pre-filled syringes that are color-coded in a rainbow pattern that corresponds to the Broselow tape we all know and love. All you have to do is discard down to the color that corresponds to the size of the child and you are sure to be giving the right dose (best explained by looking at a picture).This study assessed the speed and accuracy of medication administration in simulated pediatric resuscitations. 10 teams consisting of physicians and nurses participated in a cross over study, so that they did one simulation with the new syringes and one without. Time to delivery of medications was quicker with the new syringes (47 versus 19 seconds, a difference of 27 seconds; 95%CI 21-33 seconds). Teams were also more accurate using the new color-coded syringes, with dosing errors occurring 17% of the time with the conventional approach and 0% of the time with the new syringes (absolute difference 17%; 95% CI 4-30%). Obviously a simulation based study is not real life – but I would actually expect more stress and therefore more errors during a real resuscitation. Bottom line: Simple. Brilliant. Worth looking into.

The same group replicated basically the same study with similar results, but this time running the simulations with paramedics:

Stevens AD, Hernandez C, Jones S, et al. Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial. Resuscitation. 2015. PMID:26247145

#4: Acute diverticulitis may not require antibiotics

I guess you could put this in the same category as medical expulsive therapy – being proven wrong. However, I think this goes a step further. This was dogma. There was only one treatment for diverticulitis, and that was antibiotics. I never even considered another option. Now I can feel the world shifting beneath my feet. Over the course of one year we went from “hey, there isn’t great evidence for antibiotics”, to “we have a large RCT that shows no benefits”, and now we even have guidelines on board. How can you not love evidence based medicine?

Shabanzadeh DM, Wille-Jørgensen P. Antibiotics for uncomplicated diverticulitis. Cochrane Database Syst Rev. 2012;11:CD009092. PMID: 23152268

This is a Cochrane systematic review that was able to identify 3 RCTs looking at the use of antibiotics for uncomplicated diverticulitis. Only one compared antibiotics to no antibiotics, the other two compared different types and courses of antibiotics. There was no difference in any of the regimens. In other words, no antibiotics was the same as antibiotics. Bottom line: Not enough to change my practice, but it is good to know that we have minimal footing to our current practice.

Chabok A, Påhlman L, Hjern F, Haapaniemi S, Smedh K; AVOD Study Group. Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg. 2012 Apr;99(4):532-9. PMID: 22290281

I included the meta-analysis a few months back, but here is a multicentre RCT of 623 adult patients with CT confirmed uncomplicated diverticulitis (defined as lower abdo pain plus fever, an elevated WBC, and CT consistent with diverticulitis but no abscess or free air) randomized to either antibiotics or not. They used pretty big gun antibiotics: either a 2nd/3rd gen cephalosporin plus metronidazole or a carbapenem or piperacillin-tazobactam. There were no statistical differences between the groups. There were 3 perforations in each group. There were 3 abscesses in the no antibiotics group compared to none in the antibiotics group. 10 patients (3.2%) that started with no antibiotics were given antibiotics eventually. There were no differences in length of hospital stays or recurrent diverticulitis. Bottom line: It may well be that we don’t need antibiotics for diverticulitis, but these patients were all treated as inpatients, so its probably not up to us to make that call.

Isacson D, Thorisson A, Andreasson K, Nikberg M, Smedh K, Chabok A. Outpatient, non-antibiotic management in acute uncomplicated diverticulitis: a prospective study. International journal of colorectal disease. 30(9):1229-34. 2015. PMID:25989930

I have previously talked about the few RCTs indicating that antibiotics might not help in diverticulitis. It is an interesting topic, so I will include new evidence as I find it. This is a prospective cohort of 155 adult patients diagnosed with acute uncomplicated diverticulitis who were managed as outpatients without antibiotics, just pain control and a diet progressing from liquids back to full, as tolerated. Of the 155 patients, only 4 patients (2.5%) failed this outpatient management strategy – which isn’t much different from what you would expect if they had been treated with antibiotics. The biggest problem with this data set is that it doesn’t represent consecutive patients. 66 patients with uncomplicated diverticulitis were seen during the study period but were not enrolled, so there could be some selection bias. There was no control, so antibiotics could have lowered complication rates further – but for the 97.5% of patients without complications, it doesn’t seem that antibiotics were necessary. Bottom line: A little more evidence indicating that antibiotics may be unnecessary for diverticulitis after all.

Stollman N, Smalley W, Hirano I, . American Gastroenterological Association Institute Guideline on the Management of Acute Diverticulitis. Gastroenterology. 149(7):1944-9. 2015. PMID: 26453777

This is the new acute diverticulitis guideline from the American Gastroenterological Association Institute (that was as hard to type as it was to read.) I found three of their recommendations interesting:

• “The AGA suggests that antibiotics should be used selectively, rather than routinely, in patients with acute uncomplicated diverticulitis. (Conditional recommendation, low quality of evidence).” (They note that so far the RCTs showing no benefit of antibiotics have been in inpatients with CT proven diverticulitis.)
• “The AGA suggests against routinely advising patients with a history of acute diverticulitis to avoid consumption of nuts and popcorn. (Conditional recommendation,very-low quality of evidence).” This is another one of those myths that we breeze over, but can really ruin patients’ quality of life
• “The AGA suggests advising patients with diverticular disease to consider vigorous physical activity. (Conditional recommendation, very low quality of evidence).” This makes sense, but it has not been part of my discharge script – until now.

#3: Sick kids look sick

I love pediatrics, but I understand these little adults scare some people. The fear of missing something dangerous, like meningitis, seems to drive a lot of testing and antibiotics “just in case”. However, this paper should be reassuring. It tells us that we do a very good job recognizing meningitis, and the few cases we miss (or that develop after we seem them) do just as well as those caught on the first visit. I think this highlights a bigger issue we need to come to terms with in emergency medicine: we cannot have a zero miss rate. It is impossible. Some patients present very atypically and others will simply become sick in the days after we see them. This is a fact we must come to terms with.

Vaillancourt S, Guttmann A, Li Q, Chan IY, Vermeulen MJ, Schull MJ. Repeated emergency department visits among children admitted with meningitis or septicemia: a population-based study. Ann Emerg Med. 2015;65:(6)625-632.e3. PMID:25458981

This is a retrospective cohort of children 30 days to 5 years old who were hospitalized with the final diagnosis of either meningitis or septicemia. They were looking specifically at the children that had bounce backs. In total, 521 children were diagnosed with meningitis or septicemia, 114 (21.9%) of whom had been seen at a hospital in the 5 days prior to that diagnosis. The children all had similar mortality, lengths of stay, and critical care use whether you diagnosed them on the first visit or on the bounce back. Furthermore, meningitis and septicemia is very rare in pediatrics. There were a total of 511 cases in all of Ontario over the entire 5 years of this study. That is 511 out of 2,397,427 ED visits in this age group, or 0.02%, and you are only missing 20% of those on the first visit. Bottom line: Emergency doctors are doing fine at diagnosing sick children. We don’t need fancy tests like CRPs or procalcitonins. Even if you miss the rare child, as long as you ensure good follow up, outcomes will be identical.

Green SM, Nigrovic LE, Krauss BS. Sick kids look sick. Ann Emerg Med. 2015;65:(6)633-5. PMID: 25536869

This is the excellent editorial that goes with the above paper. I just wanted to include a few quotes:

“A second explanation, simpler and more plausible, is that sepsis or meningitis was not present at the initial visit. The first diagnoses of nonserious viral or bacterial infections were not in error; however, after discharge these children had the rare misfortune of an unanticipated progression of illness.” Ie, don’t kick yourself too hard if you have a bounceback

“The study data of Vaillancourt et al suggest that, outside of the neonatal period, sepsis and meningitis are not occult conditions and that, accordingly, “sick kids look sick.” ”

“The status quo is working.”

“These results encourage emergency physicians to trust the power and value of their clinical gestalt.”

#2: Not all PEs are really PEs

This topic reminds me that, not matter how cool our technology is getting, tests are not perfect. The PE literature from the last year included studies that demonstrate a high rate of false positive CTs, the uncertainty of the official radiology read, and the problem of improved technology that changes the definition of disease (by diagnosing smaller and smaller clots that we have no idea how to treat). There are no simple answers here, but some important lessons: Tests are not perfect. You must understand your pretest probability. And second opinions might help, even in radiology.

Miller WT, Marinari LA, Barbosa E, et al. Small Pulmonary Artery Defects Are Not Reliable Indicators of Pulmonary Embolism. Ann Am Thorac Soc. 2015. PMID: 25961445

In this study, they took all of the CT scans that were read as positive for PE in one radiology system, and had the scan review by 4 subspeciality thoracic radiologists. 15% of scans read as showing a subsegmental PE by community radiologists were thought to be false positives by the specialists. Another 27% were thought to be indeterminate. This only represents disagreement among radiologists and not the inherent false positives of the test itself. Bottom line: A positive CT scan is not an objective finding. Before subjecting patients to lifelong anticoagulation, a second opinion on the read might be warranted.

Hutchinson BD et al. Overdiagnosis of Pulmonary Embolism by Pulmonary CT Angiography. Am J Roentgenol. 2015; 205(2): 271-7. PMID: 6204274

The patient was low risk, but you decided to order the CT anyway. Thank goodness you did, because it is positive for a PE. Well, not so fast. This is a retrospective look at 937 CTPAs for PE over 1 year at a single center. They had 3 blinded radiologists review each study, using their consensus as the gold standard. Of the 174 studies that were initially read as positive, these radiologists disagreed with that read (thought it was a false positive) in 45 cases (25.9%). This is consistent with multiple other studies. Bottom line: We are likely harming many patients with unnecessary lifelong anticoagulation. In borderline cases, it might be worth asking for a second opinion on the read of the CT.

Morgan C, Choi H. BET 1: Do patients with a clinically suspected subsegmental pulmonary embolism need anticoagulation therapy? Emergency medicine journal : EMJ. 32(9):744-7. 2015. PMID: 26293150

What is the evidence for treating subsegmental pulmonary emboli? This review identified 2 observational trials that included patients with subsegmental PEs who were not anticoagulated. Of the total of 47 patients with untreated subsegmental PEs, none had recurrent venous thromboembolism at 3 months. It would not be surprising if the harms of anticoagulation outweighed the benefits, but 47 patients can’t give enough information to decide either way. Bottom line: We still really don’t know what to do, but any treatment benefit is likely to be small.

Kearon C, Akl EA, Ornelas J et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline. Chest. 2016. [free full text]

This is a new guideline from the American College of Chest Physicians covering antithrombotic therapy for VTE. The recommendation to know about: “For subsegmental PE and no proximal DVT, we suggest clinical surveillance over anticoagulation with a low risk of recurrent VTE (Grade 2C).”That’s right – they are suggesting NOT treating certain PEs! They also recognize the high false positive rate of CTPA, which I have discussed here before. When is a subsegmental PE likely to be a true positive? “We suggest that a diagnosis of subsegmental PE is more likely to be correct (i.e. a true-positive) if: (1) the CT pulmonary angiogram (CTPA) is of high quality with good opacification of the distal pulmonary arteries; (2) there are multiple intraluminal defects; (3) defects involve more proximal sub-segmental arteries (i.e. are larger); (4) defects are seen on more than one image; (5) defects are surrounded by contrast rather than appearing to be adherent to the pulmonary artery; (6) defects are seen on more than one projection; (7) patients are symptomatic, as opposed to PE being an incidental finding; (8) there is a high clinical pre-test probability for PE; and D-Dimer level is elevated, particularly if the increase is marked and otherwise unexplained.” The best way to avoid this dilemma all together is still to avoid ordering CTs in low risk patients. Bottom line: Not all PEs are really PEs. Not all PEs require treatment.

#1: A better approach to PEA

I love this article. I love it so much, I wrote an entire blog post about it. Admittedly, it’s just a concept paper. There is no prospective evidence it helps. It doesn’t matter. This immediately changed the way that I think about and teach PEA. This approach is simple. I could never remember the Hs and Ts during a code, but this algorithm is easy to recall. However, that’s not the real reason that I love it. The Hs and Ts provided no therapeutic guidance, and often provoked PEA nihilism. This new approach pushes me towards treatment. Rather than passively considering the Hs and Ts, I am now actively pursuing reversible causes. Wide complex: empiric calcium and bicarb. Narrow complex: fluids and ultrasound to find the mechanical problem. It is my favorite paper since starting First10EM.

Littmann L et al. 2014. A simplified and structured teaching tool for the evaluation and management of pulseless electrical activity. Medical Principles and Practice. 23:1-6. PMID:23949188 [free full text]

The standard epinephrine and push treatment is actually associated with worse outcomes in PEA. To that end, most guidelines say that in PEA the essential action is to determine the underlying cause.  But the Hs and Ts are hard to remember during a code, and also don’t tell you which cause is the most likely. This new algorithm does through 3 simple steps: 1) QRS wide or narrow? 2) Ultrasound to find cause (Or use clinical judgement) 3) Empiric treatment based on the first 2. This is not one where my summary will suffice – its a 4 page paper and its free. I strongly suggest taking 20 minutes and reading it through. (Or, you can read the First10EM blog post: The simplified approach to PEA) Bottom line: There is a better way to approach PEA