The Skeptics Guide to Emergency Medicine

Date: April 4th, 2023 Reference: Vaughan and Browne. Reconfiguring emergency and acute services: time to pause and reflect. BMJ Qual Saf. 2023 Apr Guest Skeptics: Dr. Louella Vaugh is an internist practising as a hospitalist physician at an academic centre in London, UK with a special interest in smaller, rural and remote healthcare. Her main job is working for a think tank. John Brown PhD is a Professor of Health Services Research in Ireland who has been studying rural healthcare issues since 2012. This is an SGEM Xtra episode. There have been many “temporary” rural emergency department closures during the past last year. In Ontario alone there have been approximately 160 emergency departments (ED) temporarily closed since the beginning of 2022. This is something that has only happened once since 2006 (Ottawa Citizen March 28, 2023) The study referred to in the editorial looks at the experience in Denmark with a reconfiguration of their emergency healthcare services (Flojstrup et al 2023). The objective of that study was the following: To investigate how the’ natural experiment’ of reconfiguring the emergency healthcare system in Denmark affected in-hospital and 30-day mortality on a national level. The reconfiguration included the centralisation of hospitals and the establishment of emergency departments with specialists present around the clock. It was a stepped-wedge reconfiguration of the entire Danish emergency healthcare system. The main outcome was the adjusted odds ratio for in-hospital mortality and hazard ratio for 30-day mortality with some pre-specified subgroups. They found no statistical difference for in-hospital mortality but slightly increased 30-day mortality. The pre-specified subgroup analyses showed a decrease in in-hospital or 30-day mortality for myocardial infarction, stroke, aortic aneurysm, and major trauma but not for pneumonia, bowel perforation or hip fractures. This was not the only study to come out of the Danish reconfiguration initiative. The dataset also reported increasing admissions, mixed results on length of stay, increasing readmission rates, increasing COPD deaths if transported by ambulance, and expected productivity benefits were not realized. The SGEM advocated for having the evidence to inform/guide our decisions. Here is what the evidence say about the centralization of emergency healthcare services from the Danish study: some possible benefits for small groups of patients (myocardial infarction, stroke, aortic aneurysm, major trauma), there was no overall improvement in the in-hospital mortality trend and a slight worsening of the 30-day mortality trend. Five Assumptions Made about Emergency Healthcare Centralization Listen to the SGEM podcast to hear Louella and John discuss the five assumptions. Listed are the assumptions and some of the points we touched upon. Assumption#1: There is a problem with the quality of EM care that needs to be fixed Boarded patients length of stay (LOS) in the ED increases mortality Canary in the coal mine (fix the mine not the canary) COVID19 and staffing It’s about a system problem not a small hospital problem Assumption#2: Smaller hospitals provide worse care than their larger counterparts Myocardial infarction, stroke, and major trauma account for 1% of ED attendance Other skilled time-sensitive interventions (abdominal, vascular, obstetrical, and intracranial surgeries) still only amount to a total of 5% of ED attendance Little or no evidence that care in small hospitals is worse for 95% of cases Assumption#3: Reconfiguration produces better outcomes While studies of centralisation of care for individual services show better outcomes for specific patient groups, the population-level evidence for whole-scale reconfiguration through changes to ED services tells a different story. Two European studies and several studies in the USA. Renee Hsia has been looking at the impact of rounds of closures in California for nearly 20 years. At least 2 other national studies were conducted in the USA. There is also good evidence relating to the impact of service closure especially on maternity services Other studies have demonstrated that hospital closures affect socioeconomic, geographical and ethnic groups differently, with the burden of closures falling most heavily on the more vulnerable Assumption#4: Remaining organizations are minimally affected by reconfiguration Evidence suggests that the remaining hospitals often suffer from substantial negative ‘spillover effects’, with overall mortality actually rising for their emergency patients ED overcrowding with consequent increases in waiting times on trollies, increases in the pressures on ambulances services (time on the road, incidents and various other forms of ‘operational strain’. The biggest problems currently facing acute and emergency services internationally are rising admissions and overcrowding; These studies strongly suggest that removing any capacity from an already overstretched system is likely to do harm. Assumption#5: Reconfiguration has other benefits and no unintended consequences Qualitative studies strongly suggest that facility closures and mergers produce permanent losses to the workforce—both to the region, as skilled workforce members move away, and permanently, as workers either retire early or seek other work The closure or downgrading of EDs in small hospitals tends to be accompanied by the removal of other ‘front door’ services, such as general medicine, general surgery and obstetrics, as well as therapy and support services. (geographical ‘deserts of care’ These predominantly impact the older and poorer patients who live in rural and peripheral communities, urban areas are not wholly immune, with burden again falling disproportionately on the most vulnerable. Health facilities are important to community identity, and their removal can lead to hidden psychological and social costs beyond the pragmatic concerns about poorer access to healthcare Rural Mailbox   Keener Contest: Last weeks’ winner was Dave Michaleson a PA. He knew the longest time a human has remained awake is 264 hours. This is not a contest and we do not want anyone to try to break this record. There is no keener contest question this week. The SGEM will be back next episode doing a structured critical appraisal of a recent publication with a keener question. We will continue to try and cut the knowledge translation window down from over ten years to less than one year using the power of social media. So, patients get the best care, based upon the best evidence. REMEMBER TO BE SKEPTICAL OF ANYTHING YOU LEARN, EVEN IF YOU HEARD IT ON THE SKEPTICS’ GUIDE TO EMERGENCY MEDICINE.

In this discussion, Dr. Justin Morgenstern, an emergency physician and creator of First10EM.com, joins Lauren Fowler, a neuroscience professor focusing on fatigue, and Dr. Emily Hirsh, an associate professor dedicated to faculty wellbeing. They dive into the critical issue of fatigue in emergency medicine, revealing its ties to shift work and how it impairs performance and patient care. Insights into managing burnout, recent research findings on fatigue assessment, and the importance of systemic changes highlight the necessity for a healthier work environment in this demanding field.

Dr. Casey Parker, a Rural Generalist specializing in emergency medicine and ultrasound, shares insights from his work between remote and urban hospitals in Australia. He discusses the effectiveness of point-of-care ultrasound (POCUS) in diagnosing biliary diseases, revealing its advantages over traditional methods. The real clinical case of a woman with abdominal pain highlights the importance of ultrasound training in emergency settings. Casey emphasizes the impact on surgical decision-making and the need for better research methods to enhance diagnostic accuracy.

Date: February 27, 2023 Reference: Walsh PS, Schnadower D, Zhang Y, Ramgopal S, Shah SS, Wilson PM. Association of early oseltamivir with improved outcomes in hospitalized children with influenza, 2007-2020. JAMA Pediatr. 2022. Guest Skeptic: Dr. Marisu Rueda-Altez is a pediatric infectious disease fellow at Children’s National Hospital in Washington, DC. She is also the President of the Junior Section of the Society for Pediatric Research. Dr. Marisu Rueda-Altez Case: A 5-year-old child presents to the emergency department in the midst of flu season with three days of fever, upper respiratory symptoms, and malaise. His parents also report that he has lost his appetite and refusing to drink liquids. Nasopharyngeal PCR testing is positive for Influenza A. On physical exam, he is tired appearing and showing signs of respiratory distress with tachypnea and accessory muscle use. His lips look dry and cracked. His oxygen saturation is hovering around 88-90%. His chest radiograph does not demonstrate any focal opacities. After a discussion with his parents, you all agree that it is best for him to be admitted to the for IV hydration and close monitoring. His parents ask you, “A few years ago when we had the flu, we took a medication that helped reduce the length of our symptoms. Would he benefit from that too?” Background: Oseltamivir is recommended by the American Academy of Pediatrics, Infectious Diseases Society of America and Center for Disease Control and Prevention for the treatment of influenza in both adults and children. [1-3] Possible benefits include reduction in duration of symptoms and improvement of outcomes in hospitalized patients. Most of these recommendations are based on data from adult studies during the H1N1 pandemic with limited pediatric data. The SGEM has covered the use of oseltamivir for influenza on SGEM #98 and SGEM #312. Despite the recommendations from these various organizations, there remains some controversy (and skepticism) about the use of oseltamivir due to unpublished trial data, lack of access to the research data by the authors, and ghost-written papers. The BMJ was involved in a long legal battle with the manufacturer that you can read about here. Suffice it to say, that there were more harms than originally reported (including nausea and vomiting, neuropsychiatric events, headaches), and it is possible that the potential benefits were exaggerated.[4] Clinical Question: Will early administration of oseltamivir reduce length of hospitalization and complications of influenza infection? Reference: Walsh PS, Schnadower D, Zhang Y, Ramgopal S, Shah SS, Wilson PM. Association of early oseltamivir with improved outcomes in hospitalized children with influenza, 2007-2020. JAMA Pediatr. 2022. Population: Children <18 year from Pediatric Health Information System (PHIS) database hospitalized with Influenza from 2007-2020. Excluded: Transfers to other hospitals, repeated encounters (if >7 days between encounters, picked one at random; if <7 days, picked the first one), death/ECMO on day 0 or 1 to avoid immortal time bias. Exposure: Early administration of oseltamivir (HD 0 or 1) Comparison: Late administration of oseltamivir (HD 2 or later) or none. Outcome: Primary Outcome: Hospital length of stay (LOS) Secondary Outcomes: 7-day hospital readmission, late ICU transfer (on or after hospital day 2 after being admitted to general ward), composite outcome of in-hospital death or ECMO use. Authors’ Conclusions: "Early use of oseltamivir is associated with shorter hospital stay and lower odds of 7-day readmission, ICU transfer, ECMO use and death." Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Unsure. Was the cohort recruited in an acceptable way? Unsure Was the exposure accurately measured to minimize bias? Unsure Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? Unsure Was the follow up of subjects complete enough? Unsure How precise are the results? Unsure Do you believe the results? Yes Can the results be applied to the local population? Yes Do the results of this study fit with other available evidence? Yes Funding of the Study: None Results: There were 55,799 patients were included, who were diagnosed with influenza by ICD 9/10 coding. Of those, 56% were male, and mean age was 3.6 years. 33,207 (59.5%) received early oseltamivir. 4,098 (7%) received oseltamivir on day 2 or later, and 18,494 (33%) were untreated. Key Result: Children treated with early oseltamivir was associated with a shorter length of stays and lower odds of 7-day readmission, late ICU transfer, ECMO use, and death. Primary Outcome Length of Stay Secondary Outcomes The Diagnosis of Influenza: The diagnosis of influenza for this study was determined by review of ICD-9 and 10 codes. The authors do cite previous research that administrative databases have high specificity (99%) and positive predictive value (60-88%) for laboratory-confirmed influenza, these two studies only looked at records from one or three institutions respectively. [5-6] The data set used in this study is significantly larger and encompasses 36 hospitals where there may be much more variation in diagnosis and coding. The gold standard for diagnosis of influenza infection is a positive nasopharyngeal PCR test. Patients could have been missed if positive and not coded as such. Also, patients who were not tested but had symptoms suggestive of influenza could have been coded as having influenza. Using ICD codes is an imperfect gold standard or copper standard. There is also possible confusion from lingering positivity of respiratory viral PCR testing as well. There was a study showed that influenza can remained positive for at least a week after symptom onset. [7] If a patient who had influenza a week ago presents now with new respiratory distress, still influenza positive, but now had a bacterial superinfection with S. pneumoniae or S. aureus. Those patients would not benefit from oseltamivir, but may still have erroneously have been coded as influenza positive, and included in the study. Duration of Illness and Timing of Oseltamivir: We had mentioned a big limitation of the PHIS database before on SGEM #384 was that it lacks clinical information. With influenza, the recommendations state that the greatest benefit in the administration of antivirals is within the first 48 hours of symptoms. However, there may still be some benefit in hospitalized patients after that period. There’s a possibility that a portion of the providers that did not treat those 33% of patients with oseltamivir may have been influenced by the duration of illness prior to presentation. Not only do we not know when the illness started, but we also don’t know when the child got started on oseltamivir prior to their presentation at the hospital. This may be the reason for why they did not receive it again during the admission. This also raises the possibility that there was a portion of patients were classified into the “early oseltamivir” group inappropriately. Exclusion due to Immortal Time Bias: The authors chose to exclude encounters with discharge, in-hospital death, or ECMO use on hospital day 0 or 1 due to immortal time bias (there is a period of time before researchers are able to classify participants as being treated). This excluded 13,641(19.2%) of eligible patients. Given the limitations mentioned prior, another interpretation of this is that there were potentially 13,641 patients for which oseltamivir had no impact on their hospital length of stay, death or ECMO. Adverse Effects: Another thing missing from this study is that it did not report any adverse effects from oseltamivir administration. The Cochrane review from 2014 that included clinical study reports from drug manufacturers demonstrated that the use of oseltamivir increases risk of nausea, vomiting (NNH of 19 in children), and psychiatric effects. Adverse effects are important when weighing the potential risks and benefits of any treatment or intervention. Future Research: The authors write “it would likely be unethical to perform a RCT of oseltamivir given the current recommendations, so observational studies such as this one are the most practical way to evaluate its use.” Observational trials allow us to establish associations and can only control for known confounding factors. I think it is fair to say that the evidence for oseltamivir is mixed at best and still very limited in the pediatric population. We should not shy away from questioning clinical guidelines or standards of care. This is important for driving progress and striving to provide the best care for our patients based on the best evidence. I do not find the idea of a randomized controlled trial unethical and would love to see a multi-center, placebo-controlled, blinded randomized controlled trial to assess the effectiveness of oseltamivir in the pediatric population. Comment on Authors’ Conclusion Compared to SGEM Conclusion: Early oseltamivir use in hospitalized children with influenza may be associated with shorter hospital LOS, and lower odds of 7-day readmission, ICU transfers, ECMO use and death but these findings should be interpreted within the limitations of study. SGEM Bottom Line: We do not have high-quality evidence to support the routine use of oseltamivir in the treatment of children admitted to hospital with suspected influenza. Case Resolution: You tell the parents that there is an option to start their child on a medication called oseltamivir.

Date: March 8, 2023 Reference: Smida et al. A Retrospective Nationwide Comparison of the iGel and King Laryngeal Tube Supraglottic Airways for Out-of-Hospital Cardiac Arrest Resuscitation. Prehospital Emergency Care 2023 Guest Skeptic: Dr. Chris Root is a third-year resident physician in the Department of Emergency Medicine at the University of New Mexico Health Sciences Center in Albuquerque, NM. He is also a flight physician with UNM’s air medical service, Lifeguard. He is a former New York City paramedic and this summer will be starting fellowship training in EMS medicine at UNM. Case: A paramedic crew responds to a 54-year-old male in cardiac arrest at a private residence. A fire company is on scene providing high-quality cardiopulmonary resuscitation (CPR) and has defibrillated twice with an automated external defibrillator (AED). The fire-based crew has basic life support (BLS) airway supplies including the King Laryngeal Tube, the paramedic crew carries iGel supraglottic airways (SGAs) in addition to their intubation equipment. They plan to use a supraglottic airway as their initial airway strategy during the arrest, but they wonder if either of these two devices is superior. Background: Airway management strategies for out of hospital cardiac arrest (OHCA) have been hotly debated since the dawn of CPR. Two large trials, PART by Wang et al and AIRWAYS-2 by Benger et al recently evaluated the King-LT and the iGel respectively as alternatives to endotracheal intubation (ETI) in cardiac arrest. Given the difficulty associated with intra-arrest endotracheal intubation, use of supraglottic airways in the prehospital setting is becoming more common. This was discussed with paramedic and physician assistant (PA), Missy Carter when critically appraising the AIRWAYS-2 trial regarding the use of the iGel in OHCA on SGEM #247 Clinical Question: Which supraglottic airway is associated with better patient outcomes, the iGel or the King-LT in patients with an out-of-hospital cardiac arrest. Reference: Smida et al. A Retrospective Nationwide Comparison of the iGel and King Laryngeal Tube Supraglottic Airways for Out-of-Hospital Cardiac Arrest Resuscitation. Prehospital Emergency Care 2023 Population: Adult OHCA patients treated by EMS contained within the ESO database from 2018-2021 who received prehospital iGel or King-LT supraglottic airway insertion. Excluded: Patients who were less than 18 years of age, pregnant, had do not resuscitate or other physician orders for life sustaining treatment, achieved ROSC after bystander CPR only, or experienced OHCA due to trauma or hemorrhage were excluded from downstream analyses Exposure: iGel Comparison: King-LT Outcome: Primary Outcome: Survival to hospital discharge home Secondary Outcomes: First-pass success, return of spontaneous circulation (ROSC), prehospital rearrest, Intrarrest ETCO2 values Type of Study: Retrospective observational Authors’ Conclusions: “In this dataset, use of the iGel during adult OHCA resuscitation was associated overall with better outcomes compared to use of the King-LT. Subgroup analyses suggested that use of the iGel was associated with greater odds of achieving the primary outcome than the King-LT when used as a rescue device but not when used as the primary airway management device.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Unsure Was the outcome accurately measured to minimize bias? Unsure Have the authors identified all-important confounding factors? Unsure Was the follow up of subjects complete enough? No How precise are the results? Adequately Precise Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Funding of the Study: No external funding sources Results: The assessed 286,192 OHCA cases for eligibility and were able to include 93,866 patients treated by 1,613 EMS agencies. iGels were inserted in 54,189 (58%) cases, and King- LTs were inserted in 39,677 (42%) cases. The average age of patients in this dataset was 63 years and 37% were female. Just over half (52%) of the 93,866 patients were transported to an emergency department. Of those transported to hospital (49,302), only 19% (9,456) had available disposition data. This means we have data on 10% of the original 93,866 patients. Among the 10% of patients that disposition data was available: 7% were discharged to home or self-care 84% died after arrival at a hospital 4% were discharged to hospice 3% were discharged to skilled nursing 7% were discharged to long-term acute care Key Result: No statistical difference in discharge home between the two devices when a supraglottic airway was employed as the initial airway management strategy. Primary Outcome: Survival to hospital discharge home Overall: adjusted Odds Ratio (aOR) 1.36 [95% CI; 1.06 to 1.76] Primary Strategy: aOR 1.26 [95% CI;0.95 to 1.68] Rescue Strategy: aOR 2.16 [95% CI; 1.15 to 4.04]) Secondary Outcomes: Use of the iGel was associated with higher first pass success with device placement, higher rates of prehospital ROSC, higher intra-arrest ETCO2 values, and lower rates of re-arrest. 1. Retrospective Data Set: This was a retrospective analysis. When retrospective data is used to answer clinical questions there is less ability to control for confounding factors than in a prospective study.  The authors attempted to control for compounding factors through their propensity scoring however any retrospective study must be interpreted cautiously. These statistical tools cannot achieve the same rigor as a properly conducted randomized control trial. 2. Discharge Home: The authors utilized discharge home as their primary outcome. This is a pragmatic choice based on the available dataset. However, it is probably not the most patient-oriented outcome (POO). Having a good neurologic outcome is likely to be more important to patients than merely surviving with a severe disability. This dataset does not provide this important information. 3. ESO Data Collaborative: The dataset comes from a software vendor of over 2,000 EMS agencies in the US. That may sound like a lot but there are over 18,000 EMS agencies in the US (EMS World 2020). Only 1,600 of the agencies voluntarily submit their data for research purposes. This could create some selection bias. In addition, only 10% of the OHCA cases in the data set had data for the primary outcome of survival to hospital discharge home. This severely limits the strength of any conclusions from the available evidence. They did provide some information on geographical region. However, there was no granularity on other factors such as urban vs rural setting or transport time to hospital. The nature of the available dataset forced the authors to exclude any patients transferred to another hospital for continuing care form their analysis which may introduce a form of survival bias. The patients analyzed may have been more likely to recover completely without requiring transfer for subspecialty care. 4. Supraglottic Airways as Primary vs Rescue Device: The authors wanted to study the difference between the King-LT and the iGel as an initial airway management device and found that both devices were associated with similar rates of discharge home. Interestingly, the iGel was associated with higher rates of discharge home when it was employed as a rescue device after failed endotracheal intubation, however in this data set the King-LT was used as a rescue device almost twice as often (12.6% iGel vs 22.4% King-LT, p < 0.001). 5. ETCO2 Waves vs Numbers: The authors utilized recorded ETCO2 data in their sensitivity analysis to evaluate the ventilatory effectiveness of each device. The data available was in the form of discrete numbers charted by the clinicians or uploaded from the EMS monitor, not continuous waveform, and these values may have been influenced by factors like minute ventilation and device leak that are not clearly captured in numeric data alone. UPDATE: March 11th, 2023 Tanner Smida We are not perfect at the SGEM and do make mistakes sometimes. The lead author, Tanner Smida, reached out to us to clarify a few things and provide some additional background information after we posted the SGEM episode. Tanner is an MD/PhD student studying at West Virginia University. He is currently in his second year of medical school and about to start his PhD in clinical and translational science. Tanner noticed some issues with our reporting of what we thought was the primary outcome. Guest skeptic Chris Root thought perhaps he made a transcription error filling out the result section of the SGEM critical appraisal form for observational studies. It may have been me confusing the primary airway device used (iGel or King-LT) with the primary outcome. When we were made aware of the issue we apologized to Tanner and invited him record a short update to the SGEM episode. He clarified the primary outcome was survival to hospital discharge home regardless of whether the supraglottic device was as the primary airway management strategy or as a rescue strategy following a failed intubation attempt. This means the primary outcome DID find superiority of the iGel over the King-LT with an adjusted Odds Ratio (aOR) 1.36 [95% CI; 1.06 to 1.76]. Tanner provided some background information about the peer review process. It was the peer reviewers who insisted on the subgroup analyses and that the results be included in their conclusions.

Date: March 3, 2023 Reference: Hosseinialhashemi et al. Intranasal Topical Application of Tranexamic Acid in Atraumatic Anterior Epistaxis: A Double-Blind Randomized Clinical Trial. Ann Emerg Med. 2022 Guest Skeptic: Dr. Dominique Trudel is a CCFP-EM resident in Ottawa, Ontario. Her interest is serving French minority communities delivering care at the Montfort Hospital in Ottawa. Case: Jim is a 50-year-old male who presents to the emergency department with anterior epistaxis. He reported it started last night in his bedroom where he used a space heater. He denies nose picking. He tried applying pressure, but it didn’t work. Vitals are stable and he is not on any anticoagulants. Background: We have covered the topic of epistaxis several times on the SGEM. The first episode was SGEM#53: Sunday Bloody Sunday. This trial looked at 216 adult patients with anterior epistaxis and randomized them to topical TXA (500mg in 5ml) compared to anterior nasal packing. The results were impressive for stopping bleeding in <10min, discharge <2hrs, rebleeding <24hrs, and patient satisfaction.  TXA is a synthetic derivative of lysine that inhibits fibrinolysis and thus stabilizes clots that are formed. It has been tried in several medical conditions and been reviewed on the SGEM. There is also a short YouTube video discussing the evidence for TXA. Trauma (CRASH-2): 1.5% absolute mortality benefit (SGEM#80) Isolated TBI (CRASH-3): No statistical difference in mortality (SGEM#270) Post-Partum Hemorrhage (WOMAN): No statistical difference in primary outcome (SGEM#214) Gastrointestinal Bleeding (HALT-It): No statistical difference in primary outcome (SGEM#301) Intracranial Hemorrhage (TICH-2 & ULTRA): No superiority for good neuro outcome (SGEM#236 and SGEM#322) That first SGEM episode on using TXA for epistaxis showing favorable results also discussed eleven questions concerning epistaxis. It’s a good overview on the management of epistaxis. The episode included the Dundee protocol for adult epistaxis management from 2012. A second RCT from the same group looked at TXA for adults with anterior epistaxis who were also taking antiplatelet medications. This too showed impressive results claiming superiority of TXA(SGEM#210). When the NoPAC trial was published, it curbed some of the enthusiasm for TXA in epistaxis (SGEM#321). It was the largest double-blinded RCT (N=496), and found no reduction in the need for anterior packing with the use of intranasal TXA. However, this trial included patients who had already failed 10 min of pressure and 10 min of packing with a topical vasoconstrictor. They also used a lower dose of TXA in the noPAC study. Another issue was that 65% of the patients were taking anticoagulants. Lastly, the primary outcome was different than the previous two RCTs claiming efficacy. These conflicting results have led to uncertainty regarding the use of TXA in patients with epistaxis. Hosseinialhashemi et al sought to provide some clarity with their trial looking at TXA in uncomplicated anterior epistaxis. Clinical Question: Should we use TXA for uncomplicated anterior epistaxis? Reference: Hosseinialhashemi et al. Intranasal Topical Application of Tranexamic Acid in Atraumatic Anterior Epistaxis: A Double-Blind Randomized Clinical Trial. Ann Emerg Med. 2022 Population: 18-year-old and older, stable patients with atraumatic anterior epistaxis, without bleeding disorders or anticoagulation. Excluded: Posterior bleeds, hemodynamically unstable, allergic to TXA; known nasopharyngeal, nasal cavity, or paranasal malignancy; pregnancy; the experience of out-of-hospital nasal packing; and epistaxis caused by trauma, known bleeding disorders, recent use of anticoagulation drugs or clopidogrel and patients who were prisoners. Intervention: Cotton pledgets soaked in TXA 500mg, phenylephrine 0.05g and lidocaine 10% x five sprays. Packing was removed after 15 minutes Comparison: Cotton pledgets without TXA but still soaked in phenylephrine 0.05g and lidocaine 10% x five sprays Outcome: Primary Outcome: Need for anterior nasal packing Secondary Outcomes: ED length more than 2h, needing electrical cauterization, rebleeding within 24h, rebleeding within 1-7 days. Type of Study: Single-center, double-blind RCT in a specialized ENT ED in Iran. Authors’ Conclusions: “Intranasal topical application of tranexamic acid is associated with a lower rate of need for anterior nasal packing and a shortened stay in the ED; it may be considered a part of the treatment for atraumatic anterior epistaxis.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. No The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Yes The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. Yes Financial conflicts of interest. No Results: They screened 315 patients and enrolled 240 patients. The patients were divided in two groups in a 1:1 ratio. The mean age of participants was 52 years, 52.5% were male and 30% were on aspirin. Key Results: TXA was superior to usual care for adult patients presenting with anterior epistasis. Primary Outcome: Need for anterior packing TXA Group 50.0% vs No TXA group 64.2% (NNT 7) Odds Ratio [OR], 0.56; 95% confidence interval [CI], 0.33 to 0.94. Secondary Outcomes:  No statistical differences between the two groups in terms of the need for electrical cauterization and the rate of rebleeding within 1 to 7 days. TXA was associated with a lower rate of stay in the ED for more than 2 hours (9.2% vs 20.8%) OR 0.38 (95% CI, 0.18 to 0.82) and rebleeding in 24 hours (15.0% vs 30%) OR 0.41 (95% CI, 0.22 to 0.78) compared with the rates in the control group. 1. Selection Bias: These were patients that from an ENT emergency department of a referral academic-teaching otolaryngology center. It is unclear if these represent the same patients who present to a community emergency department. You could argue that patients with more severe nose bleeds would present to this subspecialized ED. If TXA works in these cases than it should work in milder cases. Or if disease severity is lower than the impact of TXA might be less and not be statistically different from usual care. 2. External Validity: The second point is related to the first nerdy point. This was not only a specialist ENT ED, but it was also a single centre study in Iran. The patient population may not have external validity to patients we see in our own EDs? 3. Standard Care: Standard care in Iran may differ from our standard care. Some places like to apply ice packs, or use different external devices to stop bleeding and a variety of intranasal medications. 4. Electric Cautery: After the treatment in both groups, bipolar cauterization was used when there was a visible bleeding site in the anterior part of the nasal cavity. Many patients required electric cautery in this trial. This included about two-thirds of the patients in both groups. This result is much higher than in my practice experience. It further suggests that these are selected patients with more severe disease and/or Iran has a different standard practice. In addition, electric cautery is not available where I've worked in multiple sites in Ontario, Canada. Perhaps those in the UK, USA, Europe, Australia/NZ and elsewhere could respond about their use of electric cautery. Electric cautery could have some potential harms. These direct harms or any other harms/adverse events were not mentioned in the manuscript. It is an unfortunate trend for studies either to under-report or not report harms at all.  How can clinicians and patients make an informed decision with only knowing the potential benefits and not knowing the potential harms? 5. Other Situations: This trial is silent on other clinical situations of epistaxis which are routinely encountered in the ED. This includes traumatic bleeding, patients on anticoagulants drugs or patients who represent to the ED with refractory bleeding. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors' conclusions but would have made a friendly amendment to qualify that it was in a select population at a subspecialized ENT ED in Iran. SGEM Bottom Line: It is reasonable to add TXA to your cotton pledgets for adults with uncomplicated anterior epistaxis. Case Resolution: Jim blew out his nose and you applied cotton pledgets soaked with vasoconstricting solution and TXA. His epistaxis resolved without the need for anterior packing. You provide him instructions to avoid nose picking, you improved patient satisfaction and ED flow. Clinical Application: If TXA is rapidly available, consider adding it to patients with atraumatic anterior epistaxis in your cotton pledgets. An NNT 7 for decreasing the need for anterior packing is clinically important, TXA is cheap, and a single topical application is very unlikely to cause harm. Dr. Dominique Trudel What Do I Tell the Patient?  Blow your nose to remove some of the blood. Then we will put a cotton pack up your nose. It will have two medications on the cotton. One medication stops bleeding by pinching off the blood vessels.

Reference: Cashen K, Reeder RW, Ahmed T, et al. Sodium bicarbonate use during pediatric cardiopulmonary resuscitation: a secondary analysis of the icu-resuscitation project trial. Pediatric Crit Care Med. 2022 Date: February 15, 2023 Guest Skeptic: Dr. Carlie Myers is Pediatric Critical Care Attending at Cincinnati Children’s Hospital Medical Center. Dr. Carlie Myers Case: A 6-month-old boy presents to the emergency department (ED) with three days of worsening cough, cold symptoms, and fever. Parents note that he has been progressively more tired and difficult to arouse. He is found to be in hypoxic respiratory failure and septic shock. Intravenous (IV) access is obtained. He is quickly intubated. Despite multiple fluid boluses, he remains hypotensive and is started on vasoactive support. His blood gas reveals a mixed respiratory and metabolic acidosis with a lactate of 5.0. Despite your best efforts, he has an episode of agitation leading to hypoxia and subsequent cardiac arrest. Your team begins high quality cardiopulmonary resuscitation (CPR). An arterial blood gas is obtained demonstrates a pH of 7.0, PaCO2 of 70, PaO2 of 28, HCO3- of 7, Base Deficit of -10, and Lactate 10.0. A team member asks if you want to administer some sodium bicarbonate (1mEq/kg). Background: We often manage patients in cardiac arrest in the ED or the intensive care unit (ICU). Apart from high-quality CPR and early defibrillation, many other interventions we try lack a strong evidence base. But that does not stop us from trying to save the patient’s life and may represent some intervention bias.[1] The SGEM has covered the use of epinephrine, vasopressin, methylprednisolone, and calcium for cardiac arrest in SGEM#238, SGEM#350, and SGEM#353. Today we are focusing on sodium bicarbonate. Sodium bicarbonate has historically been used during CPR with the goal of alkalizing blood pH and treating metabolic acidosis. There are a few key assumptions about the use of sodium bicarbonate.  Low pH decreases cardiac function and responsiveness to catecholamines. Sodium bicarbonate administration will increase the pH. The increase in pH will lead to improved responsiveness to catecholamines and cardiac function. But it’s not that straightforward. Many of the studies supporting these claims were conducted on animal models or in vitro. [2] It is unclear if we see the same effects of acidosis and sodium bicarbonate in vivo. HCO3- + H+ ↔ H2O + CO2 Rapid bicarbonate infusion can cause an imbalance in CO2 across the cell membrane. HCO3- + H+ converts to H2CO3 and then to CO2 +H20. Extracellular CO2 rises rapidly, it diffuses across cell membranes and the reverse reaction occurs H2O + CO2→ HCO3- + H+; therefore, creating intracellular acidosis. There was a lack of evidence about the benefits and potential harm from using sodium bicarbonate in cardiac arrest [3], so it was removed from the American Heart Association’s (AHA) guidelines. The latest guidelines from the AHA in 2020 state, “clinical trials and observational studies since the 2010 guidelines have yielded no new evidence that routine administration of sodium bicarbonate improves outcomes from undifferentiated cardiac arrest and evidence suggests that it may worsen survival and neurological recovery.” [4] This association seems to hold true in the pediatric literature as well. [5-6] Clinical Question: What is the association between sodium bicarbonate use and pediatric in-hospital cardiac arrest mortality and morbidity? Reference: Cashen K, Reeder RW, Ahmed T, et al. Sodium bicarbonate use during pediatric cardiopulmonary resuscitation: a secondary analysis of the icu-resuscitation project trial. Pediatric Crit Care Med. 2022 Population: Pediatric patients 37 weeks to 18 years of age who received chest compressions across 18 pediatric intensive care units (PICU) or pediatric cardiac intensive care units (PCICU) from Oct 2016 to March 2021. Excluded: Children were excluded if prior to the arrest, they had terminal disease and were not expected to survive, documented lack of commitment to aggressive ICU therapies, brain death, and out of hospital cardiac arrests. Additionally, in the secondary analysis patients on extracorporeal membrane oxygenation (ECMO) at the time of CPR were excluded. Intervention: Sodium Bicarbonate administration during CPR Comparison: No sodium Bicarbonate administered during CPR Outcome: Primary Outcome: Survival to hospital discharge Secondary Outcomes: Return of spontaneous circulation (ROSC), survival to hospital discharge with favorable neurologic outcome (Pediatric Cerebral Performance Category [PCPC] of 1), functional status at the time of discharge using the Functional Status Scale (FSS), and presence of a new morbidity defined as worsening from baseline FSS by 3 or more points. Authors’ Conclusions: “Sodium bicarbonate use was common and associated with lower rates of survival to hospital discharge.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Unsure. Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? Unsure. Was the follow up of subjects complete enough? Yes How precise are the results? Unsure Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Financial Conflicts of Interest: No Results: 1,100 CPR events were included in the study. Approximately half (48%) received sodium bicarbonate. The median age was 0.63 years (IQR 0.19-3.81 years) and 53.5% were male. The most common pre-existing medical condition was respiratory insufficiency. Key Result: Sodium bicarbonate use had no association with ROSC and was associated with lower survival to hospital discharge and lower survival to hospital discharge with favorable neurologic outcomes. Primary Outcome: Survival to hospital discharge was 42.2% in patients who received sodium bicarbonate vs 73.3% (aOR 0.7, 95% CI; 0.54-0.92) Secondary Outcomes: ROSC: Sodium bicarbonate use had no association Survival to hospital discharge favorable neurologic outcomes and new morbidity 1)Patient Population: There are a few things to say about the cohort included in this study. One issue was excluding patients who were terminal and not expected to survive the hospitalization. It can be difficult at times to predict when patients will die. This subjective exclusion criteria could have introduced some selection bias. Another issue is a large portion of the patients included in this analysis had underlying are medical or surgical cardiac disease (58%) that included congestive heart failure, pulmonary hypertension, congenital heart disease, and single ventricle heart disease. Sodium bicarbonate was used more commonly in PCICU compared to those in the PICU.  These were in-hospital cardiac arrests. If outcomes with bicarb were this poor in the hospital (a better place to experience cardiac arrest than out of hospital), this doesn’t bode well for sodium bicarbonate use for out of hospital cardiac arrests. 2) Time Dependent Propensity Matching: The time dependent propensity matching of bicarbonate administration was not available in original database. The patients in this study may have received bicarbonate at different times. In the presence of time-varying treatment or exposure (HCO3), the conventional method (propensity scoring is traditionally time fixed) may cause bias because subjects with early and late exposure are treated as the same. Any patient receiving HCO3 was treated the same, regardless of the time frame the HCO3 was administered. After time-dependent propensity matching, the matched cohort can be analyzed with conventional Cox regression model or conditional logistic regression. For more information on propensity score matching, you can read Peter Austin’s introductory article on the topic. [7] 3) Confounding Factors: This was an observational study with only measured confounding factors that could be controlled for with adjustments. It means we can only conclude associations from this data not causation. Sodium bicarbonate use was associated with prolonged resuscitation time and additional pharmacologic interventions during CPR (epi, atropine, calcium, vasopressin, amiodarone, lidocaine, and fluid boluses). Sodium bicarbonate was also used more often in children with higher (Pediatric Risk Mortality Score) PRISM and VIS (Vasoactive Inotropic Score)– both markers of severity of illness. Were outcomes worse in the group receiving sodium bicarbonate because of the sodium bicarbonate or because the length of resuscitation was longer, the patients were sicker, and what about all the other medications or interventions? 4) Futility: When it comes to using sodium bicarbonate in cardiac arrest, we’ve heard some clinicians say, “well what’s the harm? The patient is dead already.” We want to caution against this mindset. This is an extremely vulnerable patient population, and our interventions should be deliberate and targeted to maximize potential benefit and reduce potential harm. Additionally, spending time performing interventions that don’t help can take away time and energy spent on performing more meaningful interventions. 5) Racial Demographics: While this study did not particularly look at variable outcomes based on race or gender of the patient, race and ethnicity are worthy demographics to report for 1) Generalizability of study findings and 2) Further examination of results in the context of equitable care.

Date: February 17, 2023 Reference: Gettel et al. Rising high-acuity emergency care services independently billed by advanced practice providers, 2013 to 2019. AEM Feb 2023 Guest Skeptic: Dr. Chris Bond is an emergency medicine physician and Assistant Professor at the University of Calgary. He is also an avid FOAM supporter/producer through various online outlets including TheSGEM. Case: You are an administrator responsible for staffing emergency departments (EDs) in a health care system comprising both urban and rural locales. The hiring pool includes emergency medicine trained physicians, non-emergency trained physicians, and advanced practice providers (physician assistants and nurse practitioners). Prior to your hiring search, you wonder how many patient encounters are being seen by each type of physician or advanced practice provider. You also wonder the breakdown of visit acuity being seen by the different provider types. Background: Advanced practice providers (APPs), primarily physician assistants (PAs) and nurse practitioners (NPs), make up more of the emergency medicine (EM) workforce each year (1-4). While APPs have traditionally focused on low-acuity patient encounters, as ED visit volumes and physician shortages increase, APPs are seeing more complex, high-acuity patients (5-6). In the United States, policies have been implemented to permit more independent APP practice, with or without direct physician support. This increase in independent service provision by APPs and change in practice pattern to more high-acuity patients has not been formally assessed (7-8). There is concern regarding the expanding practice pattern of APPs, and a March 2022 Guideline by the American College of Emergency Physicians (ACEP) stated that PAs and NPs should not perform independent, unsupervised care in the ED setting (9). Given current workforce limitations, it is not feasible to continue current 24/7 staffing models in certain EDs and communities without APPs (1,3). Similarly, many rural Canadian emergency departments have reduced their open hours or closed over recent years due to inadequate staffing (MacLean's Magazine - Dr. Alan Drummond) There are both NPs and PAs working in Canadian EDs currently and we could see their role increase in the future should staffing shortages increase. The SGEM has done two previous podcasts on APPs in the ED. These focused on productivity, safety and diagnostic testing differences between emergency physicians and APPs (SGEM#308 and SGEM#316). Clinical Question: How has the role of APPs in the provision of emergency care changed in recent years? Reference: Gettel et al. Rising high-acuity emergency care services independently billed by advanced practice providers, 2013 to 2019. AEM Feb 2023 Population: Emergency care providers including emergency physicians, non-EM physicians and APPs (Physician assistants, nurse practitioners, certified nurse midwives, certified registered nurse anesthetists) who provided fee-for-service Medicare in the United States emergency departments from 2013 to 2019. Exclusion Criteria: Providers who received less than 50 total reimbursements within a study year for evaluation services reflecting typical emergency critical care codes. Exposure: Patient encounters by APPs Comparison: Patient encounters by Physicians Outcome: Primary Outcome: Proportion of high acuity encounters independently billed by different emergency clinician types over time. Secondary Outcomes: Variation in clinicians seeing high acuity encounters based on geography (urban vs. rural). Proportion of Evaluation Management services provided by each clinician that were high, moderate or low acuity in comparison to the total number of cases seen. Type of Study: Observational study using a repeated cross-sectional analysis of emergency clinicians using the Centers for Medicare & Medicaid Services (CMS) Provider Utilization and Payment Data Practitioners Public Use File (PUF), Dr. Cameron Gettel This is an SGEMHOP and we are pleased to have the lead author on the show. Dr. Cameron Gettel is an Assistant Professor in the Department of Emergency Medicine and a Clinical Investigator at the Yale Center for Outcomes Research and Evaluation. In these roles, he primarily conducts geriatric-related and health services research Authors’ Conclusions: “In 2019, APPs billed independent services for approximately 1 in 6 high acuity EDencounters in rural geographies and 1 in 11 high acuity ED encounters in urban geographies, and well over one-third of the average APPs’ encounters were for high acuity E/M services. Given differences in training and reimbursement between clinician types, these estimates suggest further work is needed evaluating emergency care staffing decision-making.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Yes Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? No Was the follow up of subjects complete enough? Yes How precise are the results? N/A Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes Funding of the Study – Institutional funding from a variety of sources including SAEM, ABEM, National academy of Medicine and others. Results: They identified 84,477 unique clinicians provided at least 50 emergency department services during one of the 2013 to 2019 study years. There were 47,323 EM Physicians, 10,555 Non-EM Physicians and 26,599 APPs. Key Results: APP independent billing for all encounter types increased over time and close to double in rural areas compared to urban practices. Primary Outcome: Proportion of high acuity encounters independently billed APPs increased from 5.1% to 9.7% Secondary Outcomes: APPs billed more high acuity independently in rural geographies, increasing from 7.3% in 2013 to 16.4% in 2019. APPs also billed more high acuity encounters in urban areas, increasing from 4.8% in 2013 to 8.8% in 2019. Conversely, EM physicians billed more rural high acuity encounters in 2013 (74.5%) compared to 2019 (66.6%). EM physicians also billed more high acuity urban encounters in 2013 (88.5%) than in 2019 (85.5%). There was a much larger relative difference in the number of encounters billed as high acuity between 2013 and 2019 by APPs as compared with EM physicians. Critical care encounters were increasingly billed independently by APPs from 2013 to 2019, increasing from 1.1% to 2.9% Listen to the SGEM podcast to hear Cameron respond to our five nerdy questions. 1. Billing: How do we prove that people are getting sicker rather than we are billing more “aggressively”? 2. Critical Care: What about the interpretation of what is critical care, can this vary by provider type (eg. an APP may consider a pneumonia critical care, while an EM physician at a major trauma centre considers it a comprehensive visit or equivalent) 3. Non-EM Physicians: Why are there ophthalmologists, psychiatrists, family medicine and other specialties included in this study? Psychiatrist, Ophthalmologist and Family Physician 4. Database Accuracy: This study only looked at Medicare fee-for-service beneficiaries. In addition, you could not separate out split/shared billing between the APP and physician. How do you think that may have impacted the results? 5. External Validity: This was a large US based study. How do you think the results would apply to other health care systems around the world like in Canada? Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions. SGEM Bottom Line: APPs are becoming an increasing part of the emergency department workforce in the United States and billing for more high acuity patient encounters. Case Resolution: You determine that your hiring strategy will include APPs as well as physicians. APPs will be providing critical care and be seeing high acuity patients. You use this information to balance hiring of APPs and EM physicians in your urban and rural sites. Dr. Chris Bond What Do I Tell the Staff? We are looking how to safely staff our urban and rural emergency departments. This will be a difficult process and adapt over time. We need to ensure that patients get the right care, by the right clinician. Their safety is a top priority, and we are all on “Team Patient”. A variety of metrics will be followed to monitor this implementation and ensure we get the right balance of APPs and physicians. Keener Kontest: Last weeks’ winner was Albert Homs. He knew Wilt Chamberlain held the title for most double-doubles in NBA history. Listen to the SGEM podcast this week to hear the keener question. If you know the answer, then send an email to thesgem@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize. SGEMHOP: Now it is your turn SGEMers. What do you think of this episode on APPs? Tweet your comments using #SGEMHOP.  What questions do you have for Cameron and his team, ask them on the SGEM blog? The best social media feedback will be published in AEM. Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine. References: Gettel CJ, Courtney DM, Janke AT, et al. The 2013 to 2019 emer- gency medicine workforce: clinician entry and attrition across the US geography. Ann Emerg Med. 2022;80(3):260-271. Nelson SC, Hooker RS.

Dr. Sean Moore, an emergency physician and Chief of Staff at Lake of the Woods District Hospital, shares insights into tackling refractory ventricular fibrillation during cardiac arrests. He discusses a case involving a health professional who suffered an out-of-hospital cardiac arrest and the innovative defibrillation techniques being tested, including double-sequential defibrillation. The conversation also delves into the complexities of research in emergency medicine, particularly in rural settings, and emphasizes the importance of adaptability in critical care practices.

Date: February 1, 2023 Reference: Wolfrum et al. Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. Circulation. September 2022 Guest Skeptic: Dr. Justin Morgenstern is an emergency physician and the creator of the #FOAMed project called www.First10EM.com Case: You are working an overnight shift at a small rural hospital. You are tidying your things in anticipation of the arrival of the dayshift when a code blue is called. A 50-year-old man who was admitted to the hospital with a non-ST elevated myocardial infarction (NSTEMI) overnight was found unconscious and without a pulse. The nurses started CPR immediately and place pads before you even arrived. The patient is in ventricular fibrillation, and you achieve return of spontaneous circulation (ROSC) on the second shock. The patient is still unconscious. A post-arrest ECG doesn’t show any signs of STEMI. At this point, the dayshift doc walks into the room and asks, “I can’t keep up with all the evidence. Are we supposed to be starting hypothermia?” Background: “Therapeutic” hypothermia took the critical care world by storm in 2002, with the simultaneous publication of two randomized control trials (RCTs) in the same issue of the New England Journal of Medicine – the Hypothermia after Cardiac Arrest (HACA) study and the Bernard study. As a very brief recap, the HACA study randomized 275 comatose adult patients with ROSC after a witnessed cardiac arrest with a shockable rhythm, a presumed cardiac origin of arrest, and a short downtime. The hypothermia group was cooled using an external device to a target temperature between 32 and 34 degrees Celsius and maintained there for 24 hours. The primary outcome was a good neurologic outcome within six months and occurred in 55% of the hypothermia group and 39% of the normothermia group (p=0.009, RR 1.40, 95% CI 1.08-1.81). This translated into an impressive NNT of 6. The six-month mortality was also improved in the hypothermia group (41% vs 55%, p=0.02) NNT 7. Key issues with this study were possible selection bias, early stopping without a clear endpoint, and a subjective outcome in a trial that was only partially blinded. The Bernard study included 77 patients with an initial cardiac rhythm of ventricular fibrillation who had achieved ROSC but were persistently comatose. It was not randomized to individual patients, but rather based on the day of the week. It was also not blinded. The primary outcome, patients with neurologic function good enough to be sent home or to a rehabilitation facility, occurred in 49% of the hypothermia group and 26% of the normothermia group (p=0.046, although when you plug the numbers into a fragility index calculator, you get a fragility index of 0 and a p value of 0.06). This give a very impressive NNT of 4. There was an NNT of 6 for mortality (51% vs 68%, p=0.16) but it was not statistically significant. For more information on the fragility index (FI) click on this LINK. Therefore, therapeutic hypothermia was introduced into clinical practice based on two small trials with multiple sources of bias. Since 2002, we have seen several larger trials that have raised questions about the value of hypothermia. We have covered the issue of cooling patients post OHCA sever times on the SGEM including the original Targeted Temperature Management (TTM) trial (SGEM#82). TTM was a multicentre RCT from 36 intensive care units (ICUs) in Europe and Australia, which enrolled 950 comatose adult patients on arrival to hospital after out of hospital cardiac arrest, regardless of the presenting rhythm. Patients all had their temperatures controlled, but they were randomized to a target of either 33 or 36 degrees Celsius. There were no statistical differences between the groups in mortality, Cerebral Performance Category (CPC), modified Rankin Score (mRS) or mortality at 180 days. The TTM2 trial was covered on SGEM#336. It was another multicenter RCT, and that time hypothermia was compared to normothermia (a goal of keeping temperatures less than 37.5). Once again, there was no statistical difference in outcomes between the two groups in all-cause mortality or neurologic function at six months. On the other hand, the HYPERION trial, which was covered in SGEM#275, was an RCT which include both OHCAs (73%) and IHCAs (27%). The trial comparing hypothermia (33 degrees) to normothermia. In that trial, there was a statistically significant improvement in their primary outcome of neurologically intact survival (10.2% TTM vs. 5.7% usual Care (absolute difference 4.5%), p=0.047 which gives an NNT of 22). The fragility index was 1 and the trial was unblinded, leaving us with significant uncertainty. Therapeutic hypothermia has also been trialed in the prehospital environment and not been found to be superior to usual care (SGEM#21 and SGEM#54). Therefore, there remains significant uncertainty about the value of therapeutic hypothermia after cardiac arrest, especially in the inpatient environment, where patients generally have better outcomes than the OHCAs we usually see in the emergency department. Clinical Question: Does hypothermia improve all-cause mortality in adult patients who remain comatose after inpatient cardiac arrest? Reference: Wolfrum et al. Temperature Control After In-Hospital Cardiac Arrest: A Randomized Clinical Trial. Circulation. September 2022 Population: Adult patients who remained unconscious (GCS <9) more than 45 minutes after inpatient cardiac arrest. Patients were eligible irrespective of cardiac rhythm or etiology of arrest. Exclusions: These can only be found in the supplemental appendix and include the following: active bleeding, suspected intracranial bleeding, immunodeficiency, severe heart rhythm disorders, known severe cognitive deficit, pregnancy, any condition that makes 6-month survival unlikely, major hemodynamic instability. Intervention: Temperature control with a target between 32 and 34 degrees Celsius for 24 hours, followed by slow rewarming. Comparison: Temperature control with a target of normothermia. No specific protocol was followed; it was just strongly recommended to avoid temperatures greater than 37.5 Celsius. Outcome: Primary Outcome: All-cause mortality at 180 days Secondary Outcomes:In-hospital mortality and favorable functional outcome after 180 days using the Cerebral Performance Categories (CPC) score <3 Type of Study: Multicentred, open-label, blinded-outcome-assessor, randomized controlled trial Authors’ Conclusions: “Hypothermic temperature control as compared with normothermia did not improve survival nor functional outcome at day 180 in patients presenting with coma after IHCA. The HACA-IHCA (Hypothermia After In-Hospital Cardiac Arrest) trial was underpowered and may have failed to detect clinically important differences between hypothermic temperature control and normothermia.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the ED. No The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Unsure The patients in both groups were similar with respect to prognostic factors. No All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No All groups were treated equally except for the intervention. Unsure Follow-up was complete (i.e. at least 80% for both groups). Yes All patient-important outcomes were considered. Yes The treatment effect was large enough and precise enough to be clinically significant. No Financial Conflicts of Interest. Several authors declared fCOIs Results: Of 1,055 patients assessed for eligibility, 249 were randomized, and 238 are included in the final analysis. The mean age was 73 years, 64% were male, 54% were on the medical ward, and 73% were witnessed arrests. Key Result: No statistical difference in all-cause mortality at six months. Primary Outcome: All-cause mortality at 180 days. 72.5% with hypothermia and 71.2% with normothermia, RR 1.03, 95% CI 0.79-1.40, p=0.89. Secondary Outcomes: No statistical difference for in-hospital mortality and favourable functional outcome after 180 days. In-hospital mortality, ICU length of stay, and hospital length of stay were all also statistically insignificant. Lack of Blinding: Although blinding a trial of hypothermia would be incredibly difficult, the lack of blinding could have a significant impact on the results. In a modern ICU, decisions about life and death are contingent on the choices of physicians, and the way we present prognosis to patients. Clinicians beliefs about the efficacy of hypothermia might have shaped their clinical decisions or how they counselled patients, and that could have biased even a seemingly objective outcome like all cause mortality. Small Study Stopped Early: This trial was supposed to include 440 patients based upon their sample size, but they only enrolled 249. The trial was stopped early for futility, but there were no predetermined criteria for this decision. The result is a study less than half the size that they calculated was required to identify a 16% absolute decrease in all-cause mortality. Even without stopping early, this study was probably under-powered. A 16% absolute decrease in all cause mortality is a completely unheard-of benefit in modern critical care, so designing a trial with that goal seems overly optimistic. (To be fair to the researchers, that was the benefit supposedly seen in the original HACA trial.) Imbalanced Groups: Perhaps because it was stopped early, the groups are not balanced at baseline.