Research

Greatest Hits in Emergency Medicine Research: 2023

Keeping abreast of all the high-impact papers in EM is no easy feat.

EMRA’s Research Committee, in partnership with other EMRA committees, has compiled a quick review of some of the most practice-affirming or practice-changing papers recently published. This is by no means a definitive list, but our summaries of these noteworthy papers will be good to know for your next shift!

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Critical Care

Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Review by Sierra F. Williams, MS, OMS-IV

This double-blind, randomized clinical trial sought to determine whether administration of calcium during out-of-hospital cardiac arrest (OHCA) improves return of spontaneous circulation (ROSC) in adults. In this trial, 397 adult patients were randomized to receive up to 2 intravenous or intraosseous doses of 5 mmol of calcium chloride (n = 197) or saline (n = 200). A dose of calcium chloride or saline was administered immediately following a dose of epinephrine. The primary outcome of the study was sustained ROSC (defined as ROSC without need for further CPR for 20 minutes), while the secondary outcome included survival and a favorable neurological outcome at 30 and 90 days, with a modified Rankin Scale score of 0-3. The trial was stopped early due to concerns of harm in the calcium group. Sustained ROSC was achieved in 19% of patients in the calcium group and 27% in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, −7.6% [95% CI, −16% to 0.8%]; p=0.09). At 30 days, 5.2% of patients in the calcium group survived compared to 9.1% of patients in the saline group (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, −3.9% [95% CI, −9.4% to 1.3%]; p=0.17). 3.6% of patients in the calcium group reached a favorable neurological outcome compared to 7.6% of patients in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, −4.0% [95% CI, −8.9% to 0.7%]; p=0.12). The study showed that administration of calcium during OHCA in adults did not improve sustained ROSC and can potentially cause harm.

Critique and Implications for Practice
Prior to the COCA trial, evidence regarding the use of calcium in OHCA has been conflicting and lacking. However, guidelines often continue to recommend its use. There is sufficient evidence to support the use of calcium in select patient populations that were not included in this study, such as hyperkalemia, hypocalcemia, and CCB toxicity. Although the results were not statistically significant due to the low power of the study, the use of calcium in OHCA appears to be correlated with patient harm that cannot be ignored. This indicates that calcium in OHCA is not suitable for all patients and should not be used routinely. It is also important to keep in mind that there has been no study to date to demonstrate that a single medication administered during cardiac arrest made a difference in survival with a favorable neurological outcome. Early, high-quality CPR in addition to early defibrillation in the appropriate patients are the only 2 treatments that have shown improvement in these outcomes.*

*Referenced First10EM and Salim Rezaie EBM review during ResusX 2022 conference


Prehospital & Disaster Medicine, Health Systems

Using the Centers for Disease Control and Prevention’s National Syndromic Surveillance Program Data to Monitor Trends in U.S. Emergency Department Visits for Firearm Injuries, 2018 to 2019

Review by Muhammad Waseem, MD, MS & David Gordon, MS3

The authors utilized a retrospective analysis of the CDC National Syndromic Surveillance Program dataset to analyze near-real time data between January 2018 and December 2019, capturing 215 million ED visits. The study used a set of ICD-9 and ICD-10 diagnosis codes and chief complaint keywords to filter for firearm injury records. Of those visits, 132,767 were firearm related (61.6 per 100,000 ED visits). This study revealed that males aged 15-24 had higher firearm injury-related ED visit rates relative to other demographic age groups. Overall, the rate of fire-arm related injury increased for all age groups between 15 and 64 years over the interval studied. Analyzed by region, the rate of ED visits for firearm injury significantly increased in the northeast, southeast, and southwest regions. These results are consistent with other studies but were able to be reported with less lag due to the study’s near real time surveillance methods.

Critique and Implications for Practice
Firearm-related injury is a major public health issue, but there is lag between when ED visits relating to firearm injury occur and when traditional reports for firearm injury are captured. This study highlights the epidemiology of firearm-related visits to the emergency department, raising awareness of the problem and noting the need for prevention strategies. The rate of firearm-related injury and presentation to the ED is only increasing. Awareness of the epidemiology of firearm injury can help target community-based public health violence prevention, facilitate training, and guide rapid response strategies. On a systems level, this method analysis can also inform resource allocation, particularly identifying where firearm visits make up a substantial portion of ED visits. In contrast to a typical 2-year data lag from traditional ED surveillance systems used to monitor firearm injury ED visits, this study utilized near-real time electronic medical record national surveillance data. Where data is available, incorporating methods that leverage real-time surveillance could provide further insight into other clinical applications as well.


Critical Care, Airway Management

Effect of Use of a Bougie vs Endotracheal Tube with Stylet on Successful Intubation on the First Attempt Among Critically Ill Patients Undergoing Tracheal Intubation: A Randomized Clinical Trial

Review by Elisa Quince DO, MS

This multicenter, randomized clinical trial assessed if utilizing a bougie or an endotracheal tube with stylet would increase the likelihood of success on the first attempt. In this study, referred to as the “BOUGIE” trial, 1,102 critically ill adults who required tracheal intubation were randomly assigned the utilization of a bougie or endotracheal tube with a stylet. The study found an 80% success rate with the utilization of the bougie versus 83% with a stylet. Overall, the study found that using a bougie did not significantly increase the incidence of successful intubation on the first attempt compared to using an endotracheal tube with a stylet.

Critique and Implications for Practice
This study challenges the perception that a provider should primarily use a bougie during difficult intubations. This perception was shaped by previous observational studies and 1 RCT concluding that using a bougie was associated with increased incidence of first-attempt intubation. It encourages providers to focus more on utilizing the method the operator is most comfortable with at that time. When comparing the BEAM trial to this study, one difference is that the BEAM trial was limited to one single emergency department in Hennepin County Medical Center, while the BOUGIE trial received data from 7 different emergency departments and 8 ICUs in the United States. Differences in training styles and experiences can lead to the differences seen in the results of these studies but can lead to the implication that for difficult intubations, how one is trained can dictate comfort level, and comfort level can lead to successful intubation on the first attempt.


Pediatric EM

Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children with Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial

Review by David Leon, MD

This study is a multi-center 2x2 RCT with children who required amoxicillin for community-acquired pneumonia (CAP), randomized to receive either 35-50 mg/kg/d or 70-90 mg/kg/d of amoxicillin for a treatment duration of 3 or 7 days. The primary outcome was if it was clinically indicated to re-treat with antibiotics for respiratory infection within 28 days after randomization. There was no significant difference between the high- and low-dose groups, nor the 3-day vs 7-day groups. The secondary outcomes addressed CAP-related symptom severity. Cough duration was slightly prolonged in the 3-day course group. No significant interaction was noted between dose and duration groups. Outpatient treatment of CAP in children with a lower dose of amoxicillin was noninferior to traditional high-dose amoxicillin, and 3-days of antibiotics was noninferior to 7-days, with respect to the need for antibiotic retreatment within a month.

Critique and Implications for Practice
For children with mild to moderate CAP who are not in need of significant support, such as those appropriate for discharge or only requiring overnight observation, it seems adequate to treat with both lower dose and shorter course of antibiotics. However, this data may not be applicable to children with severe CAP. Local antibiogram and resistance must be considered given that the study only included amoxicillin. This is of particular interest as there was a nationwide shortage of amoxicillin this year.


Cardiology

CT or Invasive Coronary Angiography in Stable Chest Pain

Review by Sandra Gad, MSc

Randomly assigned 3,561 patients (56.2% female), follow-up was complete for 3523 (98.9%). Major adverse cardiovascular events occurred in 2.1% in the CT group and in 3% of the ICA group (hazard ratio, 0.70; 95% confidence interval [CI], 0.46 to 1.07; P=0.10). Major procedure-related complications occurred in 0.5% of the CT group and in 1.9% of the ICA group (hazard ratio, 0.26; 95% CI, 0.13 to 0.55). Angina during the final four weeks of follow-up was reported in 8.8% of the patients in the CT group and 7.5% of those in the ICA group (odds ratio, 1.17; 95% CI, 0.92 to 1.48). The DISCHARGE trial group found that the incidence of major adverse cardiovascular events did not differ between the CT group and the invasive coronary angiography group in patients with stable chest pain.

Critique and Implications for Practice
CT can be a reliable option with similar diagnostic abilities to ICA when diagnosing CAD in patients with stable chest pain. Using CT can significantly reduce patients’ concerns regarding the invasive nature of ICA, as well as alleviate the financial burden associated with ICA. Further, CT can speed up diagnosis and ensure timely treatment.


Critical Care

Sodium Bicarbonate Use During Pediatric Cardiopulmonary Resuscitation: A Secondary Analysis of the ICU-RESUScitation Project Trial

Review by Nathan Dreyfus, MD

This multi-center, retrospective cohort analysis compared the outcomes of pediatric in-hospital cardiac arrest cases (p-IHCA) between patients who received intra-resuscitation sodium bicarbonate and those who did not. Children analyzed were those who received chest compressions between ages =>37 weeks post-conceptual age and <= 18 years between October 2016 to March 2021. Various child characteristics including their Pediatric Risk of Mortality score (PRISM) and Vasoactive Inotropic Score (VIS) were collected across 10 clinical sites. The main outcome of investigation was the duration of survival to hospital discharge. Other outcomes included ROSC, neurological outcomes, and presence of new morbidity. It was shown that sodium bicarbonate was used more in children with cardiac diagnoses, increased severity of illness and longer CPR duration. Of 1,100 CPR events, use of sodium bicarbonate was associated with lower rates of survival to hospital discharge and discharge with favorable neurologic outcomes.

Critique and Implications for Practice
While the propensity-weighted model in this study omits several potential confounders, the results echo similar recent papers in adult populations providing evidence against the routine or indiscriminate use of sodium bicarbonate for cardiac arrest. One limitation is that sodium bicarbonate use was more common in medical and surgical cardiac patients than non-cardiac patients, as well as with children with higher PRISM and VIS scores which could contribute to the poorer outcomes seen. Intra-arrest lab values such as pH were not analyzed so it is unknown how sodium bicarbonate would play a role for severe intra-arrest metabolic acidosis. Also, the time to first sodium bicarbonate administration was not analyzed which could pose limitations. Although sodium bicarbonate remains a part of the ACLS and PALS guidelines for cardiac arrest, its utility is not evidence-based per this study as well as per other studies. I will be thoughtful about when I choose to administer sodium bicarbonate during code situations, as this study suggests there might even be harm in doing so.


Prehospital & Disaster Medicine, Critical Care

One and Done Epinephrine in Out-of-Hospital Cardiac Arrest? Outcomes in a Multiagency United States Study

Review by Luke Wohlford, MD, MPH

A pre- and post-intervention study investigating patient outcomes when comparing the existing protocol of epinephrine every 3-5 minutes in non-traumatic cardiac arrest to a 1-time epinephrine dosing protocol. Adults included in this study among 5 North Carolina EMS agencies were assessed for survival to hospital discharge and ROSC pre- and post-implementation. After controlling for patient factors, the single-dose approach demonstrated comparable survival to discharge rates (adjusted odds ratio 0.88, 95% confidence interval 0.77–1.29), but with lower rates of ROSC (adjusted odds ratio 0.58, 95% confidence interval 0.47–0.72). With neurological outcomes as the more patient-centered outcome, an argument can be made about the validity of a 1-time epinephrine dosing protocol.

Critique and Implications for Practice
Further work and additional studies may need to be done to further elucidate neurological outcomes among those with survival to hospital discharge, this study demonstrates equipoise with a 1-time epinephrine dosing protocol that may allow higher proportions of time spent on CPR during resuscitations and free up more resources for high-quality cardiac arrest care.


Toxicology

Performance of the Paracetamol-Aminotransferase Multiplication Product in Risk Stratification After Paracetamol (Acetaminophen) Poisoning: A Systematic Review and Meta-Analysis

Review by Mason Jackson, MD

This systematic review and meta-analysis evaluated the acetaminophen cross-product as a marker of hepatotoxicity. The cross product is calculated by multiplying the higher of the aminotransferases (AST or ALT) by the acetaminophen concentration and can be used to determine hepatotoxicity risk in scenarios excluded by the original acetaminophen overdose studies, which primarily looked at single dose, acute and timed overdoses. Target measurements were a lower threshold of 1,500 and upper threshold of 10,000. When used as a diagnostic predictor of hepatotoxicity, and hepatotoxicity in staggered ingestions, and ingestions older than 8 hours, the cross product produced a lower limit OR of 31 to 85 and a higher limit OR of 99 to 367. This demonstrates that the acetaminophen cross product is a strong diagnostic tool that can aid the emergency physician in acute acetaminophen overdose alongside the Rumack-Mathew nomogram, generating profound changes in diagnostic certainty.

Critique and Implications for Practice
In patients presenting with staggered overdoses or delayed presentation of an acetaminophen overdose, utilization of the cross product will help decide the need for N-acetyl cysteine in the ED. It serves as a useful marker for intensivists and toxicologists caring for these patients on inpatient services as well.


Medical Education

Communicating Diagnostic Uncertainty at Emergency Department Discharge: A Simulation-Based Mastery Learning Randomized Trial

Review by Hannah Seyller, MD, and Kay Nicole Tipton, DO, MS

This multi-center randomized control trial examined the ability of resident physicians to communicate diagnostic uncertainty through simulated patient encounters. Though many patients leave the ED without a formal diagnosis, residents have little training communicating diagnostic uncertainty to their patients.

In this trial, 109 residents participated in a simulation-based learning curriculum that included online modules, a mobile learning application, and 3 simulated telehealth practice sessions with a standardized patient. Participants were divided into immediate and delayed intervention groups, which did not receive the intervention curriculum until after the second patient encounter. The primary outcome was each physician’s “mastery” of communicating diagnostic uncertainty after the second encounter based on the Uncertainty Communication Checklist.

Regardless of training site or stage of training, residents in the immediate access group showed an increased mastery compared to the delayed group, who had not yet received the intervention. Two-thirds of participants felt the curriculum increased their communication skills, and 60-65% said they applied skills they learned to their clinical practice. Limitations include unblinded participants and internal development of the objective scoring tool used to determine mastery.

Critique and Implications for Practice
Residents are often not properly trained on how to communicate diagnostic uncertainty with patients. This article provides a framework that can be implemented in current or future practice within residencies to improve communication at discharge when the exact cause of patients’ symptoms remains unknown. Although the article did demonstrate a difference between early and late intervention groups within the measurement of the study, it did not show a difference when translated to clinical practice. Further studies will need to be performed to evaluate how this framework and others can affect clinical practice in emergency departments.


Critical Care

Effect of Moderate vs. Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest. The CAPITAL CHILL Randomized Clinical Trial

Review by Charles Sanky, MD, MPH

This single-center, double-blinded, stratified, randomized-controlled, clinical superiority trial was the first study to compare hypothermia at 31°C with 34°C in survivors of out-of-hospital cardiac arrest. It sought to determine whether this difference in moderate versus mild hypothermia improved clinical outcomes in comatose survivors of out-of-hospital cardiac arrest. Patients were randomly assigned to temperature management with a target body temperature of 31 °C (n = 193) or 34 °C (n = 196) for a period of 24 hours. Outcomes included all-cause mortality, ICU length of stay, neurological outcome, and adverse effects. This study found no significant difference in the composite of mortality and poor neurological outcome, occurring in 48.4% (31°C group) and 45.4% (34°C group), 95% CI, −7.2% to 13.2%; P = 0.56. However, the 31°C group had a 3-day longer median length of stay in the ICU (10 vs. 7 days; 95% CI -1.2 to 4.1; P=0.004).

Critique and Implications for Practice
Numerous studies have suggested that going beyond the targeted temperature management of 32 to 36 degrees, the updated post-cardiac arrest TTM guidelines. Studies have consequently attempted to determine what the optimal temperature might be, including the much larger TTM trial in 2021, which did not find a difference in normothermia versus hypothermia. Still, the impact on ICU length of stay is concerning, possibly reflecting that moderate hypothermia could mask fevers that otherwise would have received treatment. This study may not change my practice yet but is worth considering in the wake of new ACLS guidelines regarding TTM.


Wilderness Medicine

A New Multi-Disciplinary Approach Supported by Accident and Field Test Data to Optimize Survival Chances in Rescue and First Aid of Avalanche Patients

Review by Chelsea McAuslan, MS4

This retrospective analysis of 1070 full avalanche burials from accident databases and large prospective field test datasets were used to develop evidence-based algorithms exclusively for the avalanche rescue environment. AvaLife provides a holistic and tailor-made tool for avalanche first aid with its consideration of adapted sequence of actions, inclusion of rescue tactical considerations, advice for cases with multiple burials where there is a shortage of resources, considerations of using recovered subjects as a resource in the ongoing rescue, the adapted definition of “injuries incompatible with life,” reasoning behind the importance of rescue breaths, and the updated BLS iCPR algorithm.

Critique and Implications for Practice
This study highlights the method AvaLife in the rescue and treatment of patients trapped from the effects of an avalanche. It provides ALS and BLS providers with the methods of triage to allow for the best chances of survival for patients who undergo entrapment. The principle of the “greatest good for the greatest number” is shown crucial in these cases of situational resource shortage. Rescuers must analyze the environment, take into consideration the forces that could prolong excavation, and proceed with appropriate survival techniques according to AvaLife Protocol in patients with injuries resulting from avalanche and burial.


Admin & Operations

The use of the word "quiet" in the emergency department is not associated with patient volume: A randomized controlled trial

Review by David Gordon, MS3

This randomized control trial evaluates if hearing the word “quiet” bears any change in patient volume and perception of the business of an ED shift. In this trial, 506 staff surveys were collected over a sample of 47 shifts. For each, a researcher approached staff members with a greeting. If the day were randomized to the intervention, the researcher asked, “Has it been quiet in here?” Three hours later, the researcher returned to the staff member to administer the survey, which assessed crowdedness of ED, feelings toward patient volume entering ED, and the belief that the word quiet affects business of the day. There was no association between the word “quiet” and increased patient volumes. However, staff members who perceived that the word “quiet” influenced patient volumes reported a perception of a more crowded ED with more patients after hearing the word “quiet.” Some staff members provided qualitative responses that shifts had “worsened” following hearing the word “quiet,” citing acutely ill patient cases they were managing.

Critique and Implications for Practice
Throughout an ED shift, someone might approach an ED staff member and ask if the day is a “quiet” day. ED providers care for patients as they enter the department, but the word “quiet” does not influence patient volume. Though this study was conducted at a single site, the methodology of the study provides a robust analysis to address a common concern among emergency department staff. Staff members who feel as though there is an increase in ED volume and business following hearing the word “quiet” likely have a preconceived belief that this is true. A staff member’s initial preconceived notions of factors that trigger business within the ED may contribute to their perceptions of the ED shift. Generalizing on the study’s results, if staff adopts a mindset that the word “quiet” does not affect patient volumes, they may perceive decreased business over the course of the shift.


Any papers we missed? Let the EMRA Research Committee know and we can discuss it at an upcoming journal club!

This list was compiled and edited by EMRA Research Committee members Charles Sanky, MD, MPH; David Gordon, MS3; Kristina Pagano, MS3; and Nathan Roberts, MD, PhD.

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