2020-2021: 21 Greatest Hits - Emergency Medicine Research Edition

It is often difficult to keep up with all of the highest impact papers in emergency medicine.

The EMRA Research Committee has compiled a quick review of some of the most practice-affirming or practice-changing papers published from September 2020 to September 2021. This is by no means a definitive list, but all of these papers will likely be good to know for your next shift!


A Randomized Trial Comparing the Efficacy of Five Oral Analgesics for Treatment of Acute Musculoskeletal Extremity Pain in the Emergency Department
This randomized control trial compared the efficacy of 5 oral analgesics for the treatment of acute musculoskeletal extremity pain. All patients were deemed to need an x-ray and be appropriate for oral pain control by the treating physician. In the end, no particular analgesic was more efficacious at 1 or 2 hours. However, there was significantly more nausea and vomiting among patients treated with opioids.

Regimens included:

  1. 400 mg ibuprofen and 1,000 mg acetaminophen
  2. 800 mg ibuprofen and 1,000 mg acetaminophen
  3. 30 mg codeine and 300 mg acetaminophen
  4. 5 mg hydrocodone and 300 mg acetaminophen
  5. 5 mg oxycodone and 325 mg acetaminophen

The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial
The largest RCT of TXA in epistaxis (496 participants) demonstrates that TXA does not provide improved benefit compared to traditional nasal packing at reducing the need for anterior nasal packing (43.7% of the experimental group still required anterior nasal packing to achieve tamponade). Limitations of the study include the studied population (primarily older men on anticoagulation), and the dose of TXA used.

Regional anesthesia on the finger: traditional dorsal digital nerve block versus subcutaneous volar nerve block, a randomized controlled trial
A prospective, multicenter, RCT of 409 ED patients compared the subcutaneous volar nerve block vs. the traditional dorsal digital nerve block. All patients had a finger injury requiring regional anesthesia for surgical treatment. Results demonstrated that numbing the thumb via a dorsal block is preferred, whereas individual fingers achieve better dorsal analgesia via the dorsal block and better analgesia on the proximal phalanx via a volar block. Overall, the dorsal nerve block gave greater anesthesia but required 2 injections and a greater amount of lidocaine.

Isopropyl alcohol nasal inhalation for nausea in the triage of an adult emergency department
A randomized, double-blind, placebo-controlled trial assessed the efficacy of isopropyl alcohol (IPA) to patients who presented to triage in the ED with the chief complaint of isolated nausea and vomiting. Patients scored 3 or higher on the nausea/vomiting numerical rating scale. Among 118 patients, 62 patients who received IPA reported improved nausea and vomiting-related symptoms vs. placebo and required less rescue treatment. This is the third RCT demonstrating the efficacy of inhaled IPA for the acute treatment of uncomplicated nausea and vomiting.



A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis
A non-blinded, pragmatic non-inferiority randomized trial of 1,552 patients with appendicitis compared quality of life at 30 days between patients treated with 10 days of antibiotics vs. appendectomy for appendicitis. The results demonstrated that antibiotics have comparable outcomes to surgery for acute appendicitis etiologies, with the exception of patients with an appendicolith who had higher rates of complications in the antibiotic group.


Prospective Validation of Canadian TIA Score and Comparison with ABCD2 and ABCD2i for subsequent stroke risk after transient ischemic attack: multicenter prospective cohort study
This prospective multicenter cohort study was designed to validate the Canadian TIA Score for patients needing risk stratification for future adverse neurologic events. Results demonstrated that among the 7,607 ED patients presenting for TIA, 1.4% had a subsequent stroke within 7 days, and 1.1% required carotid endarterectomy/stenting. The Canadian TIA score outperformed the ABCD2 and ABCD2I in risk stratifying patients with an improved area under the curve. The Canadian TIA risk score was also able to identify a low-risk cohort appropriate for rapid outpatient evaluation. The Canadian TIA score is now validated and can be used in clinical practice.

MAGraine: Magnesium compared to conventional therapy for treatment of migraines
The single-center, prospective, double-blinded, randomized, three-armed trial compared magnesium, metoclopramide, and prochlorperazine for the treatment of migraine. This study found that magnesium was not inferior in efficacy to the other two medications, which can be especially useful in patients who simultaneously present with prolonged QT. However, patients who received magnesium for migraine management were more likely to require additional analgesia subsequently. One significant limitation of this study is that it was stopped early due to COVID, causing it to be underpowered, with n = 157.


Effect of a Restrictive vs Liberal Blood Transfusion Strategy on Major Cardiovascular Events Among Patients With Acute Myocardial Infarction and Anemia: The REALITY Randomized Clinical Trial
An open-label, noninferiority, randomized trial attempted to identify an optimal transfusion strategy in patients with acute myocardial infarction and anemia. Primary outcome was major 30-day adverse cardiovascular events. The study concluded that among the 668 participants, between the restrictive (transfuse at HgB ≤ 8) and liberal transfusion groups (transfuse at HgB ≤ 10), major adverse cardiac events occurred in 11.0% of patients in the restrictive group vs. 14.0% in the liberal transfusion group. The authors concluded that a restrictive transfusion resulted in a noninferior rate of MACE after 30 days with a relative risk of 0.79 (1-sided 97.5% CI, 0.00-1.19). They also cautioned that the non-inferiority confidence interval was large enough to contain worse outcomes in the restrictive group, warranting a larger study to confirm these results.

 DIagnostic accuracy oF electrocardiogram for acute coronary OCClUsion resuLTing in myocardial infarction (DIFOCCULT Study)
This is a retrospective case-control study evaluating the performance of EKG STEMI criteria or expanded EKG Acute Coronary Occlusion Myocardial Infarction(ACOMI) criteria for the identification of Acute Coronary Occlusion. In this study, 1,152 STEMI and 2,353 non-STEMI patients were evaluated. In the non-STEMI group 28% were found to have an acute coronary occlusion identifiable on EKG with ACOMI criteria. These non-STEMI patients with ACOMI had similar mortality rates to STEMI patients. The author shows that a refined EKG paradigm for the identification of acute coronary occlusion would have improved sensitivity to identify those who need acute reperfusion therapy.

Effects of Fluoroquinolones on Outcomes of Patients With Aortic Dissection or Aneurysm
This was a retrospective cohort study that compared patients who were diagnosed with aortic aneurysms or aortic dissections and their mortality risk after fluoroquinolone exposure. Patients were identified after their initial hospitalization and then outpatient data was followed, looking at prescription days of fluoroquinolones (experimental group) or amoxicillin (negative control group) and then monitored for adverse outcomes. The study concluded that exposure to fluoroquinolones was associated with a higher risk of all-cause death (adjusted hazard ratio [aHR]: 1.61; 95% conīŦdence interval [CI]: 1.50 to 1.73) as well as aortic-related death (aHR: 1.80; 95% CI: 1.50 to 2.15). Increasing evidence has shown fluoroquinolones should be avoided in high-risk patients unless no other treatment options are available.


The ED-AWARENESS Study: A Prospective, Observational Cohort Study of Awareness With Paralysis in Mechanically Ventilated Patients Admitted From the Emergency Department
The single-center, prospective cohort study assessed the prevalence of awareness with paralysis in ED patients receiving mechanical ventilation. In this study, 383 patients were surveyed following extubation for awareness during paralysis. The study identified a prevalence of 2.6% (10/383), with rocuronium usage at any point resulting in higher instances of awareness (70%) vs. all other paralytics (31.4) (95% confidence interval 0.94 to 8.8). While there are many possible reasons for this prevalence, it is much higher than the rate observed in general anesthesia (~1%), and care should be taken to start appropriate and timely post-intubation sedation.

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
This is an open-label randomized control trial of 1,850 adults with an out-of-hospital cardiac arrest who subsequently underwent targeted hypothermia (at 33°C), or targeted normothermia. Primary outcome was mortality at 6 months. Functional outcomes at 6 months were also evaluated. The study concluded 50% of the patients treated with hypothermia died, compared to 48% of the normothermic group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P = 0.37). Similarly, 55% of patients in the hypothermic group suffered from severe disability (modified Rankin scale score ≥4), compared to 55% of normothermic patients (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09), thus concluding that targeted hypothermia does not decrease mortality within 6 months when compared to targeted normothermia. This study should be narrowly interpreted, as it is a highly selected patient population that does not compare well to the general U.S. cardiac arrest population in regard to rates of bystander CPR, rates of presenting with a shockable rhythm, and neurologically intact survival rates.

Lung-Protective Ventilation and Associated Outcomes and Costs Among Patients Receiving Invasive Mechanical Ventilation in the ED
A retrospective study assessed how ventilation settings in the ED affected ICU outcomes among 4,174 patients. In this study, 58.4% of patients on ventilation received lung-protective ventilation in the ED (defined as tidal volume ≤ 8mL/kg predicted body weight) and were less likely to suffer from ARDS (aOR, 0.87; 95% CI, 0.81-0.92) or in-hospital death (aOR, 0.91; 95% CI, 0.84-0.96). ED ventilatory care of critically ill patients can have lasting effects on mortality and other adverse outcomes.

Early head-to-pelvis computed tomography in out-of-hospital circulatory arrest without obvious etiology
In patients who present following an out-of-hospital cardiac arrest, identifying obvious causes can be challenging and not immediately identifiable. A prospective, observational pilot study assessed the safety and efficacy of early head-to-pelvis CT imaging to identify the cause of cardiac arrest. Among 104 patients a sudden death CT scan (SDCT) protocol (non-contrast CT head, ECG-gated cardiac and thoracic CT angiogram, and nongated venous-phase abdominopelvic CT angiogram) identify the cause of cardiac arrest in nearly 39% of patients. In addition, life-threatening complications of resuscitation were identified in 16% of patients. Though exploratory, these findings suggest that a sudden death CT protocol can expedite the diagnosis of potential causes and identify resuscitation complications in patients with out-of-hospital cardiac arrests.

Noninvasive Ventilation Use in Critically Ill Patients with Acute Asthma Exacerbation
A retrospective cohort study assessed the association between noninvasive ventilation and a subsequent need for invasive mechanical ventilation and in-hospital mortality among patients admitted to the ICU with an asthma exacerbation. Noninvasive ventilation was associated with a lower likelihood of receiving invasive mechanical ventilation (adjusted generalized estimating equation odds ratio, 0.36; 95% CI, 0.32-0.40) and decreased in-hospital mortality (odds ratio, 0.48; 95% CI 0.40-0.58) unless patients had concomitant comorbid pneumonia and/or severe sepsis.


Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia: The SAFER Randomized Clinical Trial
A multicenter, blinded, non-inferiority RCT compared rates of cure for community-acquired pneumonia with a short course (5 days) vs. standard course (10 days) of amoxicillin. In this study, 281 pediatric ED patients between 6 months and 10 years old with CAP who were being discharged were randomized. The results demonstrated that the short course of antibiotic therapy was comparable to longer course antibiotics. Clinical cure occurred in 88.6% in the short group and 90.8% in the control group (risk difference, -0.016; 97.5% confidence limit, -0.087). In pediatric patients who are otherwise healthy presenting with community-acquired pneumonia, it is reasonable to consider a shorter course (< 10 days) of antibiotics and follow-up with primary care physician to ensure clinical cure. Though these results are consistent with other trials, the results themselves are not as robust, and an additional trial is likely needed with different endpoints to confirm these findings.

Risk Factors and Outcomes After a Brief Resolved Unexplained Event: A Multicenter Study
To evaluate whether current American Academy of Pediatrics risk criteria predict BRUE outcomes, a multicenter retrospective cohort study assessed more than 2,000 infants less than 1 year of age who presented with a suspected BRUE without a probable alternative or definite diagnosis. Among these patients, 87% met AAP higher-risk criteria for having at least 1 AAP risk factor; 63% were hospitalized, with the most common explanations being less serious such as GERD (18.5%), choking or gagging (8.2%), viral respiratory infections (4.4%), and breath-holding spells (4.1%). A serious diagnosis was identified in 4.0% of patients, with 45% of these diagnoses being made after discharge from the index visit without an explanation. Having at least 1 AAP risk factor (ie, higher-risk criteria) was associated with a recurrent event in the ED or hospital (odds ratio [OR] 5.9; 95% confidence interval [CI] 2.7–12.6) and a recurrent event that led to an explanation (OR 15.1; 95% CI 2.1–108.6). The results suggest that while the absence of AAP high-risk criteria had a robust NPV (97%) for underlying serious conditions, the presence of criteria did not have a strong PPV (4%).

Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old
This paper represents the first official guidelines from the American Academy of Pediatrics for the evaluation of well-appearing febrile(≥ 38°C) infants 8-60 days old. These landmark guidelines are divided into three algorithms for infants 8-21 days of age, 22-28 days of age, and 29-60 days of age. There is an abundance of information in this paper and it is worth becoming familiar with and having handy for when this situation arises. Importantly, there are inclusion and exclusion criteria listed to ensure kids are appropriate for utilization of these guidelines.


Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury: A Double-blind, Placebo-Controlled, Randomized Clinical Trial
Pragmatic, phase 3, multicenter, double-blind, placebo-controlled, superiority randomized trial which assessed clinical outcomes among 6559 patients at risk for hemorrhage who received prehospital tranexamic acid (single dose). The 30-day all-cause mortality was assessed among patients who received 1g TXA (treatment) or 100 mL saline (placebo) prior to hospitalization. Results showed 30-day mortality among patients receiving TXA was 8.1% vs. placebo 9.9% (95% CI, -5.6% to 1.9%; P = .17). Post-hoc analysis, stratified by time to TXA administration, showed giving TXA within 1 hour of injury in patients with severe shock lowers 30-day mortality compared with placebo (18.5% vs 35.5%; difference, -17%; 95% CI, -25.8% to -8.1%; P < .003). 


Diagnostic Accuracy of Lung Point-Of-Care Ultrasonography for Acute Heart Failure Compared with Chest X-ray Study Among Dyspneic Older Patients in the Emergency Department
A retrospective cohort study assessed whether POCUS was comparable to chest x-ray in identifying acute heart failure exacerbation among older patients. An 8-zone lung ultrasound protocol was used to look for signs of pulmonary edema; 148 patients were enrolled. For the diagnosis of acute heart failure, POCUS had a sensitivity of 92.5% and a specificity of 85.7% vs. chest x-ray with a sensitivity of 63.6% and specificity of 92.9%. Overall, POCUS had a significantly higher sensitivity for the diagnosis of acute heart failure, while demonstrating comparable specificity.

Impact of point-of-care ultrasound on treatment time for ectopic pregnancy
A retrospective, observational, cohort study assessed whether transabdominal POCUS by itself or in addition to consultative radiology ultrasound (RADUS), reduces ED treatment time for patients with ectopic pregnancy requiring operative care. Among 109 patients admitted with ectopic pregnancies, 36 received POCUS (with 23 of those 36 also receiving RADUS), and 73 received RADUS only. POCUS involved the RUPTURE exam (Right Upper and Pelvis Timley Ultrasound for Ruptured Ectopic) to evaluate for an intrauterine pregnancy and abdominal free fluid. The average ED treatment time in the POCUS group was 157.9 min vs. 206.3 min in the RADUS group (p = 0.0141). The median time to OR for ruptured ectopic pregnancies was 203.0 min (interquartile range [IQR] 159.0) in the POCUS group versus 293.0 min (IQR 139.0) in the RADUS group (p = 0.0002). These results conclude that POCUS was associated with significantly faster time to OR for ectopic pregnancies.

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