The Skeptics Guide to Emergency Medicine

Date: October 3, 2025 Reference: Doheim et al. Meta-Analysis of Randomized Controlled Trials on IV Thrombolysis in Patients With Minor Acute Ischemic Stroke. Neurology 2025 Guest Skeptic: Dr. Casey Parker is a Rural Generalist, Evidence-based medicine enthusiast and Ultrasound Nerd. This episode was recorded live, in beautiful Broome, Australia, at the Spring Seminar on Emergency Medicine (SSEM 2025). You can get copies of the slides used in the presentation at this LINK. You can also watch the episode on YouTube. Case: Dani is a recently retired emergency department (ED) doc who has spent the last year travelling the world, playing banjo & sharing time with family and friends. This morning, whilst eating a breakfast of eggs and ham, Dani had a sudden onset of right-hand weakness and difficulty speaking. Dani’s family called 000 (911 in North America), and she was taken to the ED within one hour. On arrival at your medium-sized rural ED, Dani is assessed by the “Stroke Team aka, you” as having mild motor weakness in the right hand and mild dysarthria. Dani is given an NIHSS score of 4. A rapid CT and CTA is quickly reported as “no acute large vessel occlusion” and “No intracranial bleed and no established cortical infarction”. You know that many centers in the city are offering intravenous tPA for patients with acute ischemic stroke.  You wonder if Dani should get a dose?  Background: Minor ischemic strokes (MIS), often defined by NIHSS ≤5, are very common, with roughly half of all ischemic strokes presenting with mild deficits. Despite the mild presentation, these strokes are not always benign. About 30% of patients with initially minor stroke symptoms end up significantly disabled (unable to walk independently) at 90 days [1].  In short, a small stroke can still have a big impact on a patient’s life if it isn’t effectively treated or if it progresses. Dr. Daniel Fatovich There have been gallons of ink spilled in the discussion of the stroke literature, with much debate on previous SGEM episodes about the relative risks and benefits of IV thrombolytic therapy for acute strokes. Drs. Ken Milne and Danny Fatovich have earned themselves the title of “non-expert EM contrarians” when discussing the literature around acute ischemic stroke management with Neurologists all over the world. IV thrombolysis (tissue plasminogen activator [tPA], or newer Tenecteplase [TNK]) is a well-established therapy for acute ischemic stroke based on some questionable evidence [2-6]. However, its role in mild strokes has been hotly debated. On one hand, treating early might prevent a minor stroke from evolving or causing hidden disability. On the other hand, tPA carries a risk of intracerebral hemorrhage, and many minor stroke patients recover well without aggressive intervention. Guidelines have wrestled with this nuance: current recommendations endorse tPA for mild strokes that have clearly disabling deficits, but advise against tPA for mild non-disabling strokes [7]. The core controversy is whether the potential functional benefit in MIS is worth the bleeding risk if the patient is already doing okay. Things changed 10 years ago after Mr. CLEAN was published. It showed that endovascular interventions (EVT) for acute large vessel occlusions (LVOs) could have impressive results (NNT of 7). However, the role of IV thrombolytics for minor stroke syndromes remains unclear and controversial.  Legendary (now-retired) ED Dr. Joe Lex once stated, “If I can kick the syringe outta’ your hand – then don’t give me the tPA!”  Was Joe right? Before 2019, practice varied widely. Some neurologists treated almost any stroke within the window, reasoning that “time is brain” even for mild deficits, while others were more conservative. Observational studies yielded mixed signals. Several studies suggested that thrombolysis in mild strokes improves the chance of an excellent outcome at discharge or 90 days, while others showed minimal benefit. The PRISMS trial (2018) was a key randomized study in this area. It compared alteplase vs. aspirin in patients with minor non-disabling strokes (NIHSS ≤5). PRISMS found no difference in 90-day functional outcomes (mRS score 0-1) between the tPA and aspirin groups, but did find an increase in symptomatic intracerebral hemorrhage with tPA [8]. However, that trial was stopped early after only ~1/3 of the planned enrolment (313/948). This was reported due to a lack of funding. There are issues with stopping trials early, which we have discussed on previous SGEM episodes. Stopping PRISMS early meant it lacked the power to definitively settle the question of lysis minor, non-disabling strokes. Consequently, equipoise remained, and actual practice often followed guideline nuance, treating “minor-but-disabling” strokes (for example, isolated aphasia or hemiparesis that significantly limits function) while generally avoiding tPA in trivial or rapidly improving strokes. Viele et al JAMA 2016, Guyatt et al BMJ 2012, Tyson et al Trials 2016 Clinical Question: In adults with minor acute ischemic stroke (generally NIHSS ≤5), does IV thrombolysis (IVT) improve functional outcomes compared with non‑thrombolytic standard care? Reference: Doheim et al. Meta-Analysis of Randomized Controlled Trials on IV Thrombolysis in Patients With Minor Acute Ischemic Stroke. Neurology 2025 Population: Adults (≥18 y) with minor ischemic stroke (NIHSS <6) eligible to receive IVT within 12 hours of onset from RCTs. Excluded: Nonrandomized studies or those without a control arm. Trials included patients with nondisabling and, in some RCTs, mildly disabling symptoms. Intervention: A variety of IV thrombolytic drugs (Alteplase, Tenecteplase, pro-urokinase) given within varying time windows, but most within 3 to 4.5 hours, followed by standard care. Comparison: Non-thrombolytic standard care (NT‑SC), which could include dual or single antiplatelet therapy, anticoagulants, statins, antihypertensives, glucose control, and other risk‑factor–directed treatments. Outcome: Primary Outcome: Excellent functional outcome at ~90 days, defined as mRS 0-1. (For IST‑3 subgroup data, OHS was converted to mRS; where only 6-month data existed, it was used.) Secondary Outcomes: Favourable outcome mRS 0-2, 90-day mortality, recurrent ischemic or hemorrhagic stroke and safety (symptomatic ICH [sICH]and any ICH). Type of Study: Systematic review and meta-analysis or RCTs  Authors’ Conclusions: “IVT does not confer improved functional outcomes among patients with minor strokes and can be associated with higher odds of sICH and mortality.”      Quality Checklist for Therapeutic Systematic Reviews: (yes/no/unsure) Was the clinical question sensible and answerable? Yes Was the search detailed and exhaustive? Yes Were primary studies of high methodological quality? Yes Were the assessments of studies reproducible? Yes Were the outcomes clinically relevant? Yes Was there low statistical heterogeneity for the primary outcomes? Unsure Was the treatment effect large and precise enough to be clinically significant? No  Who funded the review? No targeted funding reported. Conflicts of interest declared? Authors report no relevant disclosures. (though not true for the primary trials - most had conflicts/funding by drug companies) Results: A total of 3,364 patients from four RCTs were included in the primary analysis. The age ranged from ~56 to 80 years across trials. Most had non-disabling deficits. Some RCTs included a minority with disabling symptoms. Trials varied in time windows (≤3 h, ≤4.5 h, ≤12 h) and imaging criteria (TEMPO‑2 required evidence of intracranial occlusion). The typical baseline NIHSS medians ~2 to 4 in the RCT. Key Results: Compared with non-thrombolytic standard care, IV thrombolysis did not improve excellent 90‑day functional outcome (mRS 0-1) and was associated with higher odds of symptomatic ICH and mortality in patients with minor stroke. Primary Outcome: mRS 0-1 at ~90 days: OR 85 (95% CI 0.70–1.03). No significant benefit of IVT vs NT‑SC. Similar null results across Alteplase, Tenecteplase, and prourokinase subgroups. Null also across disabling and nondisabling presentations.  Secondary Outcomes: mRS 0–2 at ~90 days: OR 71 (95% CI 0.55–0.91). Lower odds of independence with IVT. It became non-significant when post hoc IST‑3 data were added (OR 0.85, 95% CI 0.58–1.24).  Symptomatic ICH: OR 10 (95% CI 2.01–12.96). Increased with IVT.  Any ICH: OR 21 (95% CI 1.63–3.01). Increased with IVT.  90‑day Mortality: OR 84 (95% CI 1.18–2.89). Increased with IVT.  Recurrent Stroke: OR 01 (95% CI 0.79–1.29). No statistical difference. What Goes Into the Sausage Machine: This meta-analysis includes a range of trials with different inclusion, exclusion criteria, differing baselines, geographic/demographic and “standard care” comparators, so it is a bit of an evidentiary fruit salad. It can be hard to know how this data applies to the patient and the drugs/system of care that you are working with in your hospital. To make this decision, we may need to look back at individual cohorts and see if they represent our patients and system of care. Rural Stroke Application: In large tertiary hospitals where access to immediate imaging, stroke teams, and endovascular “clot retrieval” interventions has become the standard of care, all of the options are available. However, in rural or remote hospitals where we often do not have as much information or access to interventional neuro-radiology, we run the risk of delivering “second-class” care to our patients with acute ischemic strokes. This trial gives us some clarification around the role of tPA in our smaller community.  Is it best to transfer patients with large, disabling strokes to a bigger centre,

Reference:  George S, et al. Effectiveness of nasal high-flow oxygen during apnoea on hypoxaemia and intubation success in paediatric emergency and ICU settings: a randomised, controlled, open-label trial. Lancet Respir Med. March 2025 Date: July 10, 2025 Guest Skeptic: Dr. Spyridon Karageorgos is a Pediatric Chief Resident at Aghia Sophia Children’s Hospital, Athens, Greece and faculty of the Pediatric Emergency Medicine MSc at Queen Mary University in London. Case: A two-year-old boy presents in the emergency department (ED) with severe respiratory distress and hypoxemia. You attempt to use some non-invasive forms of respiratory support, but he continues to have significant work of breathing and retractions. His mental status begins to decline, and he appears much sleepier than before. The team makes the decision to intubate him. You follow the steps of the pre-intubation checklist and pre-oxygenate him with 100% FiO2. As the sedative and paralytic for intubation are given, the respiratory therapist asks, “Do you also want to use nasal high flow (NHF) for apneic oxygenation during intubation?”  Background: Managing hypoxia in pediatric patients in EDs and intensive care units (ICUs) remains a challenge. Hypoxia can arise from various causes, including bronchiolitis, pneumonia, asthma, or undifferentiated respiratory failure. Ensuring timely and effective oxygenation is critical to stabilizing these patients and preventing progression to respiratory failure or cardiac arrest.  NHF oxygenation has gained traction as a respiratory support modality in both ED and ICU settings. NHF delivers humidified and heated oxygen at high flow rates, which typically exceed the patient’s inspiratory flow through nasal cannula. This mechanism not only improves oxygenation but can also help reduce the work of breathing by flushing anatomical dead space and providing some degree of positive end-expiratory pressure (PEEP). The use of NHF is considered less invasive than continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) or mechanical ventilation. It is usually better tolerated, especially by children. The use of NHF has expanded into general pediatric practice, especially for treating conditions like bronchiolitis and other forms of acute respiratory distress. But, its comparative efficacy to standard oxygen therapy in various clinical settings and patient populations remains a subject of ongoing investigation. While we would always prefer a controlled intubation, sometimes the patients we see in the ED are unstable and need to be intubated emergently. We often try to pre-oxygenate prior to intubating to maximize oxygen reserves. Previous studies have suggested that the use of NHF may reduce the risk of hypoxemia and improve first-attempt intubation . However, randomized controlled trials evaluating this practice in the pediatric population are limited. Clinical Question: In children requiring emergency intubation, does the use of nasal high-flow oxygen for apneic oxygenation reduce hypoxemia and increase the rate of successful first-attempt intubation compared to standard care? Reference:  George S, et al. Effectiveness of nasal high-flow oxygen during apnoea on hypoxaemia and intubation success in paediatric emergency and ICU settings: a randomised, controlled, open-label trial. Lancet Respir Med. March 2025 Population: Children aged 1 month to 15 years with acute hypoxic respiratory failure (SpO₂ <92% on room air) requiring emergency endotracheal intubation in EDs and pediatric and neonatal ICUs across Australia, New Zealand, and Switzerland. Exclusion: Primary nasal intubation, blocked nasal airways, elective endotracheal tube change, intubation required immediately for loss of cardiac output or respiratory arrest, location of intubation outside of ED or ICU, death Intervention: Nasal high-flow oxygen at 2L/kg/min during the apneic phase of intubation. Weight HFNC rate 0-12 kg 2L/kg/min (max 25 L/min) 13-15 kg 30L/min 15-30 kg 35L/min 30-50 kg 40L/min >50 kg 50L/min Comparison: Standard care Outcome: Primary Outcomes: Hypoxemia (SpO2 ≤90% or difference of ≥10% if they were unable to achieve a pre-intubation saturation of 100% or the patient had cyanotic congenital heart disease with a right to left shunt) and first-attempt intubation success without hypoxemia Secondary Outcomes: Total intubation attempts, re-oxygenation needs, duration of ventilation, lowest oxygen saturation throughout intubation period, length of stay, mortality, adverse events. Trial: Randomized controlled, open-label, pragmatic multicenter trial Dr. Shane George Guest Author: Dr. Shane George is a paediatric emergency and critical care physician at Gold Coast University Hospital, Australia. That’s right he’s trained in both emergency medicine and paediatric intensive care. He’s the lead for children’s critical care research for Gold Coast Health which is affiliated with the University of Queensland and Vice Chair of the Paediatric Research in Emergency Departments International Collaborative (PREDICT)  Authors’ Conclusions: The use of NHF during emergency intubation in children did not result in a reduction in hypoxaemic events or an increase in the frequency of successful intubation on the first attempt. However, in per-protocol analysis, there were fewer hypoxaemic events but no difference in successful intubation without hypoxaemia on first attempt. Barriers to the application of NHF during emergency intubation and the reasons for abandoning intubation attempts before physiological compromise should be further investigated to inform future research and recommendations for intubation guidelines and clinical practice. 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). Unsure The patients in both groups were similar with respect to prognostic factors. Yes 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. Unsure Financial conflicts of interest. The funders (Fisher & Paykel Healthcare) provided equipment that was used during the trial but did not have a role in study design, data collection, data analysis, data interpretation, or writing of manuscript. Three of the authors reported consultancy fees, travel, and accommodations by the same company. Results: They included 969 children with 535 assigned to NHF and 534 assigned to the standard care group. Key Results: There was no statistical difference in hypoxemic events or first attempt intubation success among patients who received nasal high flow compared to standard care. Primary Outcome: Hypoxemia occurred in 61 (12.8%) of the NHF group compared to 77 (16.2%) of the standard care group (aOR 0.74; 97.5% CI 0.46-1.18, p=0.15). First attempt successful intubation without desaturation occurred in 300 (63%) of the NHF group compared to 280 (59.1%) of the standard care group (aOR 1.13; 97.5% CI 0.79-1.62, p=0.43). They also did a per protocol analysis where 45 of the intubations were removed. Hypoxemia occurred in 48 (10.8%) of the NHF group compared to 77 (16.7%) of the standard care group (aOR 0.59; 97.5% CI 0.36-0.97, p=0.017). First attempt successful intubation without desaturation occurred in 284 (64%) of the NHF group compared to 268 (58.1%) of the standard care group (aOR 1.22; 97.5% CI 0.87-1.71, p=0.19). Secondary Outcomes:   There were no statistical differences in intubation attempts, need for re-oxygenation in between intubation attempts, duration of mechanical ventilation, length of ICU or hospital stay. The rates of minor and major adverse events were similar as well. Tune in to the podcast to hear Dr. George answer our questions. Biases In this study, approximately 14% of eligible patients were not approached for inclusion due to the treating clinician’s discretion. This is separate from those who were not approached for social or compassionate reasons. Another 14% were missed for unknown reasons. This could have introduced selection bias. Do you have any insights on why the treating clinicians chose not to approach certain patients? How do you think this may have impacted the study results? The open-label design (lack of masking) meant neither clinicians nor evaluators were blinded, introducing potential performance and detection bias. What impact to you think that may have had on the trial? Standard Care When we looked at the protocol deviations in the study. It looks like there was more non-compliance in the NHF group, with most of the reasons being that clinicians seemed to have forgotten to put on the NHF. Did you happen to collect data on what “standard care” meant to clinicians involved in the study? Modified Intention-to-Treat (mITT) vs Per-Protocol (PP) Analysis  You performed two different analyses for the data: Modified Intention-to-Treat (mITT) and Per-Protocol (PP) analysis. Each type of analysis has some strengths and weaknesses. Why did you not perform a pure ITT? Your team did find a statistical difference in the rate of hypoxemia between the two groups based on the analysis performed with the per protocol analysis favoring the use of NHF.

Date: September 18, 2025 Guest Skeptic:  Dr. Neil Dasgupta is an Emergency Medicine (EM) physician and emergency department (ED) intensivist from Long Island, NY. He is the Vice Chair of the ED and Program Director of the EM residency program at Nassau University Medical Center in East Meadow, NY.  Reference:  Doupnik et al. Impact of telemental health on suicide prevention care in U.S. emergency departments. AEM Sept 2025 Trigger Warning: The following case scenario discusses suicide and self-harm. If you or someone you know is at risk, seek immediate help (dial 911/999/112 as appropriate, or 988 in the US/Canada for suicide & crisis support). Resources:  Substance Abuse and Mental Health Services Administration (SAMHSA) National Alliance on Mental Illness (NAMI) American Foundation for Suicide Prevention (AFSP) Case: It’s 23:15 on a Tuesday in a 10-bed rural emergency department (ED) that serves as the community’s sole hospital. A 37-year-old male arrives with a friend after texting that they “can’t do this anymore.” The friend is concerned because he has access to firearms. Triage vitals are stable. The nurse uses the ED’s standard suicide‑risk screen, which is positive. The nurse activates the service’s 24/7 telemental‑health workflow. A video cart is wheeled into the room, and a remote clinician joins the conversation. Background: Delivery of quality mental health care is one of the major difficulties affecting our EDs. Caring for these patients presents a particular kind of challenge, since establishing rapport with the patient, getting a detailed history, gathering collateral information from others, overcoming possible intoxications or toxidromes, requiring staff for continuous observation and treating physical injuries can require substantial levels of time and skills.  In addition, suicide remains a leading cause of death, and EDs are a frequent point of contact for people in crisis. Many of these encounters involve complex psychosocial factors, limited outpatient capacity, and time-sensitive safety planning. The stakes are high, and what happens in the ED can shape risk in the hours to days after discharge. As emergency physicians, we balance therapeutic alliance, thorough risk assessment, and efficient disposition in an environment built primarily for acute medical care, not longitudinal mental health follow-up. Frustration often occurs due to limited resources, high volumes, inpatient boarding and overcrowding; it can seem impossible for an ED physician to provide compassionate, nuanced, complete psychiatric care. Patients utilize the ED for mental health care because they often do not have a choice.  Sometimes that lack of choice stems from a report of suicidal thoughts, which in most communities represents a lack of capacity to make medical decisions, and EMS systems are required to transport these patients for emergent psychiatric care.  In many communities, especially in areas that have less robust access to health care in general, there are profound administrative, financial and systemic barriers to creating or maintaining a functional level of mental health care infrastructure, profoundly overburdening the services that exist and pushing those needs onto the local emergency departments.  Telemedicine (particularly telepsychiatry and broader telemental health) has become a pragmatic way to expand access to mental health expertise. This has accelerated with the pandemic-era virtual care. Programs vary widely, with some providing on-demand psychiatric prescribers, while others lean on social work, psychology, or case management. Integration with the ED team and the electronic health record (EHR) can be excellent in some settings and minimal in others. Despite legislative progress in the US, including the Affordable Care Act and the Addiction Equity Act, reimbursements remain poor for the care of such patients, severely limiting access to care.  As with many other challenging issues, for lack of a better option, the ED becomes the entryway to any portion of the healthcare system. For rural and critical‑access hospitals, telemedicine can be the difference between no specialist input and round-the-clock access. But the question that matters to front-line EM clinicians is not just “Is telehealth available?” It’s “Does telehealth meaningfully improve the way we deliver suicide‑prevention care in the ED?”And, even if processes improve, do those changes translate into better patient-oriented outcomes (POO) such as reduced attempts, ED revisits, or suicide deaths? Clinical Question: Among US hospital-affiliated EDs, is having access to telemental health associated with greater routine use of recommended suicide‑prevention practices? Reference:  Doupnik et al. Impact of telemental health on suicide prevention care in U.S. emergency departments. AEM Sept 2025 Population: 606 EDs in the US associated with a general medical hospital Excluded: EDs in government hospitals (VA/DoD), specialty hospitals (orthopedic), rehabilitation hospitals, and independent children’s hospitals (surveyed separately). Freestanding EDs not affiliated with a general hospital. Exposure: ED use of telemental health (telepsychiatry/telemental services available to the ED).  Comparison: EDs without telemental health. Analyses stratified by critical‑access hospital status and adjusted for ED/hospital characteristics.  Outcome: Primary Outcome: Routine use of six recommended suicide‑prevention practices Assessment of current suicidal intent/plans Past suicidal thoughts/behaviours Access to lethal means Standard approach to discharge planning Routinely scheduling follow-up Lethal‑means restriction counselling. Secondary Outcomes: Prevalence and characteristics of ED telemental health programs (staffing, hours, and EHR integration). Type of Study: A National cross-sectional survey with stratified probability sampling and nonresponse weighting. Dr. Stephanie Doupnik This is an SGEMHOP, and we are pleased to have the lead author on the episode, DrStephanie Doupnik is an Assistant Professor of Pediatrics and Health Policy and Director of the Division of Pediatric Hospital Medicine at Vanderbilt University Medical Center. Dr. Doupnik’s research has been funded by the National Institute of Health and focuses on the implementation of mental health services and suicide prevention care in EDs and hospitals, including the use of telehealth. Authors’ Conclusions: “Telemental health care is widely used across all types of EDs, and EDs with telemental health care are more likely to use suicide prevention practices. Critical-­access hospitals rely on telemental health care to a great extent and need better access to telehealth psychiatry and EHR information sharing. Quality Checklist for Reporting of Survey Studies (Yes/No/Unsure)? Were hypotheses or aims explicitly stated? Yes Were operational definitions of the predictor (independent) and outcome (dependent) variables provided? Yes Were participant eligibility criteria (inclusion and exclusion) explicitly stated? Yes Were participants recruited using an acceptable recruitment strategy? Yes Were participants selected by a random/probability sampling strategy? Yes Was the sample size appropriate? Unsure Were participants randomly assigned into groups/ conditions? N/A Was the response/participation/recruitment rate provided? Yes Was the attrition rate acceptable? Unsure Was the attrition rate treated appropriately in data analyses? Yes Were the chosen statistical tests appropriate to address hypotheses or research questions? Yes Did the study include a formative research or pilot phase? Yes Were the measures provided in the report (or in a supplement) in full? Yes Were all measures of established validity, or was a validation procedure undertaken by the authors? Unsure Was the study sample described in terms of key demographic characteristics? Yes Was the data collection process described with sufficient detail for it to be replicated? Yes Were generalizations of findings restricted to the population from which the sample was drawn? Yes Was the study approved by a relevant institutional review board or research ethics committee? Yes Did participants provide informed consent (or assent, where relevant)? Yes Were funding sources or conflicts of interest disclosed? Yes  Results: Of 977 eligible EDs, 606 responded (62%), weighted to 4,321 EDs nationally. Responders more often were rural, smaller, and critical‑access hospitals with nonresponse weights applied. Overall, 68% of responding EDs reported using telemental health. Lower ED volume, smaller bed size, and critical‑access status were associated with higher telehealth use. Key Result: Over two-thirds of US emergency departments use telemental health. Secondary Outcomes:  Availability: More than 80% of telehealth EDs reported 24/7 coverage, with critical‑access EDs reporting they were more likely to have 24/7 access (81% vs 64%).  Staffing: Telepsychiatrists/prescribers available in 68% of non-CAH programs vs 54% in CAHs. CAHs relied more on private contractors/other systems.  EHR Integration: Telehealth clinicians could view the EHR in 64% of non-CAHs vs 28% of CAHs; documentation privileges 64% vs 35%.  Post‑ED Follow‑Up: Only about one quarter of programs provided any follow-up after discharge. Listen to the SGEM podcast to hear Stephanie answer our five nerdy questions. Self‑Report & Social Desirability Bias: Outcomes were ED leaders’ reports of “routine” practice. Without chart audits or direct observation, overestimation is plausible, especially for practices perceived as best‑practice (lethal‑means counselling). How did you mitigate this issue?

Date: Sept 16, 2025 Reference: Prada et al. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. August 2025 Guest Skeptic: Dr. Andrew Martin is an emergency physician practicing in Jacksonville, Florida.  Case: A 27-year-old at 24 weeks’ gestation presents to the emergency department (ED) with fever (38.6 °C), myalgias, and sore throat. She took 650 mg of acetaminophen (Tylenol) six hours ago with partial relief. She hesitated to repeat the dose after reading online posts about “Tylenol and autism.” She has no abdominal pain, no vaginal bleeding, and normal fetal movement. Vitals otherwise stable; pharynx erythematous, no exudate. She asks, “Is it safe to take another dose, or could this hurt my baby’s brain later?” Background: Acetaminophen (paracetamol) is the most used analgesic–antipyretic in pregnancy. A recent prospective cohort study suggests ~40 to 65% of pregnant people report using it. They are typically using acetaminophen for headache, myalgias, or fever, with most use being short and intermittent. Alternatives, particularly non-steroidal anti-inflammatory drugs (NSAIDs), carry well-described fetal risks in late gestation. This is one of the reasons why acetaminophen remains the default first-line choice [1,2]. Biologically, acetaminophen crosses the placenta and achieves fetal levels like maternal levels, making the developing brain theoretically exposed during critical windows [3]. This has motivated a large observational literature examining whether prenatal exposure is linked to later neurodevelopmental outcomes such as ADHD and autism. Meta-analyses generally report small associations (summary effects around 1.2 to 1.3) and signal stronger effects with longer duration of use, though heterogeneity in exposure measurement and outcome ascertainment is substantial.  Professional bodies, including the American College of Obstetricians and Gynecologists (ACOG) and the Society of Obstetricians and Gynecologists of Canada [SOGC], continue to recommend acetaminophen for appropriate indications at the lowest effective dose and shortest duration. At the same time, they do acknowledge ongoing research and the limitations of observational data (including confounding by indication). For emergency clinicians, the practical tension is familiar. The dilemma is that untreated maternal fever and significant pain can themselves harm pregnancy, yet patients are increasingly asking about possible long-term neurodevelopmental potential harms of using acetaminophen.  Clinical Question: Is acetaminophen exposure during pregnancy associated with ADHD, ASD, or other neurodevelopmental disorders (NDDs) in children? Reference: Prada et al. Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology. Environ Health. August 2025 Population: Observational studies assessing children of pregnant individuals for neurodevelopmental outcomes. Excluded: Postnatal exposures, non-human studies for the primary analysis, non-original publications, and duplicate reports from the same cohort. Exposure: Prenatal acetaminophen (maternal self-report, biomarkers such as meconium/cord blood, or medical records/prescription registries). Comparison: Children who were not exposed prenatally to acetaminophen, or those exposed to alternative analgesics. Outcome: Primary Outcome: NDDs (particularly ADHD and ASD) and related symptomatology measured by clinical diagnoses, medication use, or validated behavioural scales. Secondary Outcomes: Timing and dose–response patterns, broader cognitive/behavioural domains (language & executive function), and triangulation across design types. Type of Study: Systematic review using the Navigation Guide methodology with a qualitative synthesis (no meta-analysis) due to substantial heterogeneity. Authors’ Conclusions: “Our analyses using the Navigation Guide thus support evidence consistent with an association between acetaminophen exposure during pregnancy and increased incidence of NDDs. Appropriate and immediate steps should be taken to advise pregnant women to limit acetaminophen consumption to protect their offspring’s neurodevelopment.” Quality Checklist for Systematic Review: The main question being addressed should be clearly stated. Yes The search for studies was detailed and exhaustive. Unsure Were the criteria used to select articles for inclusion appropriate? Yes Were the included studies sufficiently valid for the type of question asked? Unsure Were the results similar from study to study? No Were there any financial conflicts of Interest? Yes Result: They searched PubMed (primary) through Feb 25, 2025, with confirmatory checks in Web of Science and Google Scholar. A total of 46 studies were included.  The studies consisted of a mix of prospective cohorts, retrospective/historical cohorts, sibling-controlled cohorts, and two case-control studies.  Sample sizes ranged from ~100 to a national registry scale (Sweden’s registry cohort included 2.5 million births). Key Result: The preponderance of studies reported positive associations between prenatal acetaminophen exposure and ADHD/ASD or related symptoms, with dose–response suggested in several biomarker and prospective cohorts. However, some sibling-controlled analyses attenuated associations toward null, and overall heterogeneity was high. Of 46 studies, 27 reported positive associations, 9 null, and 4 inverse (protective) associations. Several higher-quality or biomarker-based studies suggested dose-response relationships. No pooling into a meta-analysis due to heterogeneity 1) Exposure Misclassification: Most contributing cohorts ascertained prenatal acetaminophen exposure via maternal self-report during pregnancy or post‑partum recall, or from prescription/registry data that do not fully capture over-the-counter use. The authors’ own risk‑of‑bias summaries flag the exposure domain as a frequent concern, and they rate retrospective self-report, especially when collected after child diagnosis, as high risk for recall bias. In contrast, biomarker studies (meconium, cord blood, maternal plasma/urine) mitigate recall bias and, in several instances, suggest dose–response, but they remain snapshots that imperfectly reflect timing and cumulative dose. The review also highlights how low-sensitivity exposure measurement can deflate associations. An example is the large Swedish sibling‑analysis cohort that reported 7.5% use based on midwife interviews, despite contemporaneous sources indicating ~50 to 60% use. This implies substantial underascertainment (misclassification bias or ascertainment bias) that likely biases the estimate toward the null and compounds loss of power in within-family models. Together, these exposure‑measurement limitations should make us more cautious in both the direction and magnitude of observed associations in the qualitative synthesis. 2) Residual Confounding: Although many included studies adjusted for a broad set of factors (maternal age, socioeconomic status, smoking, alcohol, illness, fever, and infection) and some used negative‑control exposure periods or propensity approaches, the review acknowledges that unmeasured and residual confounding remain possible. Importantly, the authors did not implement a quantitative bias analysis (E‑values, probabilistic bias analysis) to bound the strength of confounding necessary to explain the findings. They explicitly list this as a limitation of the review. Given that indications for acetaminophen (fever, pain, intercurrent infection) may themselves relate to neurodevelopmental outcomes and can be difficult to measure with sufficient granularity, any qualitative conclusion about “persistence after adjustment” should be interpreted skeptically. 3) Outcome Heterogeneity & Variable Ascertainment:  The review pools evidence across disparate outcome definitions: registry-based clinical diagnoses (ICD‑coded ADHD/ASD), ADHD medication use, and multiple validated behavioural scales (CBCL, SDQ), often at different child ages and with parent vs teacher report. This heterogeneity in outcome measurement (plus differences in timing of assessment) creates non-comparability that complicates causal interpretation and precludes valid pooling. Appropriately, the authors do not conduct a meta-analysis, citing the substantial heterogeneity in exposure assessment, outcome measures, and confounder adjustment. Risk‑of‑bias summaries also show concerns in the outcome domain for some outcome types. Mixing clinical diagnoses, proxy markers (medication), and symptom scales across varied ages increases measurement error and between-study variability, limiting the precision and generalizability of the qualitative synthesis. 4) Search Scope & Evidence‑Grading: The search strategy relied on PubMed as the primary database with confirmatory checks in Web of Science and Google Scholar. No additional eligible studies were identified beyond PubMed, and no discussion of searching the grey literature.  Heavy reliance on a single primary database risks missing studies indexed elsewhere or gray literature, potentially introducing retrieval bias.[4] In addition, while the Navigation Guide offers a structured approach, the authors note that its numeric domain‑averaging can imply unwarranted precision and assign equal weight to domains even when certain biases (confounding, exposure error) likely dominate. They attempted sensitivity analyses (excluding lowest‑scoring papers and up-weighting confounding) but acknowledge the framework’s default “moderate” rating for observational evidence could skew certainty assessments. These methodological choices reasonably reflect transparency but also represent limitations of the review’s grading and synthesis.

Date: August 12, 2025. This is an SGEM Xtra, and today, we’re putting on our conference lanyards and boarding passes to talk about one of the most exciting events in the global EM calendar, IncrEMentuM 2026. For those who did not attend IncrEMentuM 2025, it set the bar incredibly high. From the moment delegates walked into the venue in Murcia, Spain, there was a buzz that felt like the early days of SMACC. The conference felt electric, global, and unapologetically fun. The talks were short, sharp, and full of energy, blending the best evidence with stories you’d remember long after the conference ended. On-stage simulations pushed the boundaries of what a medical conference could be, while debates in the concourse were full of healthy skepticism. Between sessions, the networking was amazing. One minute you could be sipping coffee next to EM legend Scott Weingart, and the next minute swapping resuscitation hacks with a new friend from across another continent. And, of course, the Spanish hospitality shone through. Paco, Carmen and the whole Incrementum team made everyone feel welcome, well fed, and everyone left wanting more. Well, you are in luck. Lightning is going to strike again on April 22 to 24, 2026, back in beautiful Murcia. Today, I am joined by three amazing Canadian EM physicians and educators who will be presenting in Murcia. Dr. Sara Gray has been known to run codes with the grace of a symphony conductor. Dr. Chris Hicks is like the Yoda of resuscitation: wise, calm, and occasionally cryptic. And finally, Dr. David Carr, the master of pearls, pitfalls, and the occasional “I-can’t-believe-that-just-happened” story. Having these three superstars on the SGEM reminds me of what a deep bench of medical educators we have in Canada. We are consistently punching above our weight in the #MedEd world. Today's podcast is not about Canada but rather the amazing things Spanish EM educators are doing. Five Questions for the Panellists Listen to the SGEM Xtra podcast to hear Sara, Chris and David respond. What can people expect from IncrEMentuM 2026? How is it different from your typical EM conference with endless PowerPoint karaoke & bad coffee? How does IncrEMentuM compare to the SMACC conferences? What will each of you be bringing to the stage in 2026 in Murcia? Beyond the great talks, why should someone hop on a plane to Murcia, and what are you looking forward to the most? IncrEMentuM 2026: April 22 to 24 in Murcia, Spain. Be prepared or be unprepared. Come for the evidence, stay for the tapas, and leave with new skills, new friends, and maybe a few “you-had-to-be-there” stories. The SGEM will be back with a structured critical appraisal, trying to cut the knowledge translation (KT) window from over ten years to less than one year, using the power of social media, so patients get the best care, based on the best evidence. Recuerda ser escéptico de todo lo que aprendas, incluso si lo escuchaste en The Skeptics’ Guide to Emergency Medicine.

Date: August 12, 2025 Article: FDA Approved and Ineffective by Jeanne Lenzer and Shannon Brownlee. June 5, 2025. The Lever. Jeanne Lenzer Guest Skeptic: Jeanne Lenzer is a long-time medical investigative journalist and returning SGEM guest. Her previous work, including the book The Danger Within Us, explored how conflicts of interest and weak evidence can endanger patient care. In this new project with The Lever, Jeanne analyzes how the FDA approves drugs that often don’t meet basic efficacy standards. I think many people assume that if a treatment is FDA-approved, surely it must work. However, people may be shocked to find out about the FDA’s drug approval process and how ineffective or harmful medications make it to market. Most patients and doctors have no idea that the FDA has quietly flipped the drug approval process on its head by putting most drugs on the market before they are shown to be safe or effective, with the promise that they will do those studies after they are on the market. Studies have shown that once a drug is on the market, patients do not want to enter or remain in clinical trials because they are convinced they’re being deprived of a proven treatment, and failure to enroll sufficient patients is one reason postmarket studies are delayed or never conducted. Once a drug is on the market, the FDA can require postmarket testing, but the due dates are often set so many years in the future that the patent will have run out. Take the controversial new Alzheimer’s drug, Leqembi, which causes brain bleeds, swelling and death. The manufacturer is required to conduct safety studies and report annually to the FDA.  However, neither the FDA nor the company will release the safety data until the final report is due. This will be in 2036, 13 years after it’s been on the market. This can be considered a guaranteed win for Pharma and a bad deal for patients. The FDA has fallen so low that the agency introduced a new term, “dangling approvals” for drugs approved before clinical benefit was proved and then allowed to remain on the market even after the post-marketing studies fail. Richard Pazdur, head of oncology at the FDA, defended the agency’s refusal to order certain cancer drugs off the market even after their post-market studies failed, saying “A failed trial, doesn’t mean a failed drug.” Well, true and true, but the idea is that drugs were supposed to be proven to work before they go on the market, not after. And with Pazdur’s and the FDA’s reasoning, any bad drug could remain on the market forever. And a few have. A two-year investigation by Lenzer and Brownlee found 429 FDA approvals (2013–2022) where the majority of drugs were authorized on inadequate evidence of effectiveness, with heavy reliance on surrogate outcomes, frequent lack of replication, and slow/absent confirmatory trials. The highlighted real-world harm and cost and call for regulators and clinicians to re-center on patient-oriented outcomes (POO) before widespread adoption. The article gives a few stories about FDA-approved drugs that turned out to cause harm without any benefit. One example was the drug Elmiron: Elmiron (pentosan polysulfate sodium) was approved in 1996 by the FDA for interstitial cystitis (chronic bladder pain) FDA approval was given without solid evidence of effectiveness FDA allowed approval on the condition that a follow-up study be done to confirm efficacy The follow-up study took 18 years to complete and showed no benefit over placebo Despite this, Elmiron remained on the market Not just a lack of benefit, but there were reported cases of harm Elmiron was associated with cases of a rare eye disease called pigmentary maculopathy that resulted in vision loss or blindness. It was also associated with severe colitis and dozens of deaths Bottom line is a drug with no proven benefit and significant harms stayed on the market for nearly 30 years A cautionary tale of systemic FDA failure to protect patients There were other examples in the articles: Avastin (bevacizumab): Initially approved for metastatic breast cancer via progression-free survival (PFS) surrogate; later trials failed to show survival benefit; approval was withdrawn for that indication, but surrogate-based oncology approvals have continued apace. Copiktra (duvelisib): Approved on surrogates; subsequent data suggested earlier death vs comparator and serious harms; FDA restrictions only years later. ProAmatine (midodrine): Repeatedly rejected; ultimately approved under Subpart H with promised post-market evidence that never convincingly materialized. Special Guest Skeptic: Dr. Jerome Hoffman. He is a longtime friend of the SGEM, a mentor and a true thought leader in evidence-based medicine (EBM). Dr. Hoffman has critically appraised stroke studies, challenged the tPA (alteplase) hype, and now serves as the analytical lead behind this FDA investigation. Four Questions for Jeanne & Jerry Listen to the podcast to hear their answers to these and other questions. What are the four standards the FDA claims to use when approving drugs? Control Group: Patients taking the drug were compared to a control group that was given a placebo or a comparator drug. Replication: At least two “well-controlled” trials showed the drug was effective. Blinding (Masking): Subjects in the studies and the doctors who cared for them don’t know which patients are on the drug and which are in the control group. Clinical Endpoint: The studies measured the drug’s effect on patients’ survival or function rather than a surrogate measure. Of the hundreds of drugs analyzed, how many meet all four?  Therefore, 44% of these drugs met two or fewer of the FDA's four core criteria for approval. 73% percent of drugs approved by the FDA did not meet the agency’s four foundational standards required to show they work as expected. More than half of drug approvals were based on preliminary data rather than sound evidence that patients had fewer symptoms, improved function, or lived longer. Fifty-five of the 429 drugs approved met only one of the four standards needed to show that a drug is safe and effective; 39 drugs met none of them. Which category of drugs seems to be the worst offender, and why? Oncology was the standout concern: of 123 cancer drugs, 2.4% (3/123) met all four criteria; 29 met none. 81% of cancer approvals used surrogates (progression-free survival) rather than overall survival. What changes are needed? Do we fix the FDA, or start from scratch? Key Take Home Points: Even giving them the benefit of the doubt, nearly ¾ of drugs failed to meet all four of the standards. Cancer drugs are among the worst, often approved on flimsy surrogate endpoints like tumour shrinkage. Elmiron, for example, stayed on the market for nearly 30 years despite never being shown to work and causing blindness in some patients. The FDA is funded largely by industry through user fees, leading to deep structural conflicts of interest. Clinicians must remain skeptical, dig deeper into the evidence, and resist the assumption that “FDA-approved” means “safe and effective.”  SGEM Bottom Line: Being approved by the FDA doesn’t mean a drug is effective or even better than a placebo. All we can conclude is that the FDA approved the drug. We need to be skeptical, look at the primary evidence, and be willing to question the system. People may not know, but the SGEM tagline came from a lecture given by Dr. Hoffman. He concluded the lecture by encouraging the audience to be skeptical, even of him.  Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine. Other SGEM Episodes: SGEM Xtra: The Danger Within Us SGEM Xtra: No Retreat, No Surrender - Thrombolysis for Acute Ischemic Stroke SGEM Xtra: Jerome Hoffman - Legend of Emergency Medicine

Reference: Jessen et al. Pharmacological interventions for the acute treatment of hyperkalaemia: A systematic review and meta-analysis. Resuscitation 2025 Date: August 6, 2025 Guest Skeptic: William Toon is a paramedic who, this past May achieved over 50 years of continuous EMS certification. His professional path has taken him from front-line paramedic to national presenter, expert witness, flight medic, EMS program director, and senior training executive with a doctorate in Higher Education. Case: A 65-year-old patient presents to the emergency department (ED) with general weakness, mild abdominal cramping, and nausea over the past 12 hours. The patient has poorly controlled type 2 diabetes, heart failure with reduced ejection fraction, and chronic kidney disease stage 4 on hemodialysis. The patient missed their last dialysis appointment two days ago. The patient takes several medications for kidney disease and blood pressure, including a potassium-sparing diuretic. His ECG shows peaked T-waves. Stat chemistry reveals a serum potassium of 6.5 mmol/L. He is not yet oliguric and is hemodynamically stable. The team must initiate pharmacologic treatment immediately while preparing for possible escalation to dialysis. Background: Hyperkalemia is a potentially life-threatening electrolyte abnormality frequently encountered in the ED. It’s common in patients with chronic kidney disease, diabetes, or those on renin-angiotensin-aldosterone system (RAAS) inhibitors. While treatments like insulin, beta-agonists, and calcium gluconate are well-known, the comparative efficacy and safety of pharmacologic agents used to rapidly reduce serum potassium remain uncertain. Clinicians must balance rapid action with safety when choosing treatment for hyperkalemia. Understanding which pharmacologic interventions work best and how quickly they act is vital to optimizing care. Unfortunately, much of the existing data on hyperkalemia treatment is derived from small or methodologically limited trials. Clinical Question: What is the effectiveness of pharmacological interventions in the acute treatment of hyperkalemia compared to standard care, placebo, or other interventions in adults? Reference: Jessen et al. Pharmacological interventions for the acute treatment of hyperkalaemia: A systematic review and meta-analysis. Resuscitation 2025 Population: Adult patients with hyperkalemia (typically defined as serum potassium ≥5.0 mmol/L). Studies included varied populations such as those with CKD, dialysis patients, and acutely ill inpatients. Exclusions: Patients under 18 and those receiving non-pharmacologic interventions (dialysis) were excluded. Intervention: Any acute pharmacological intervention to mitigate the harmful effects of hyperkalemia or to lower potassium levels. Comparison: Placebo, standard care, or head-to-head comparisons of other pharmacologic interventions. Outcome: Primary Outcome: Change in serum potassium from baseline at specific time points (1, 2, 4, and 6 hours). Secondary Outcomes: Proportion of patients achieving normokalaemia, adverse events (hypoglycaemia), need for rescue therapy (dialysis), and all-cause mortality. Type of study: Systematic review and meta-analysis Authors’ Conclusions: “Evidence supports treatment with insulin in combination with glucose, inhaled or intravenous salbutamol, or the combination. No evidence supporting a clinical effect of calcium or bicarbonate for hyperkalaemia was identified.” Quality Checklist for Therapeutic Systematic Reviews: The clinical question is sensible and answerable. Yes The search for studies was detailed and exhaustive. Yes The primary studies were of high methodological quality. No The assessment of studies were reproducible. Yes The outcomes were clinically relevant. Yes There was low statistical heterogeneity for the primary outcomes. No The treatment effect was large enough and precise enough to be clinically significant. Yes Who funded the trial? No financial support was provided for the study. Did the authors declare any conflicts of interest? No relevant conflicts of interest disclosed. Results: Studies included adult patients with hyperkalemia from EDs, inpatient wards, and dialysis units. Ages ranged widely, with a predominance of patients with chronic kidney disease (CKD) and cardiovascular comorbidities. Key Result: Sodium zirconium cyclosilicate and insulin-glucose regimens were most effective in lowering serum potassium within four hours, while other agents had limited short-term impact. Primary Outcome: At four hours, insulin-glucose reduced potassium by an average of 0.8 mmol/L, and sodium zirconium cyclosilicate by 0.67 mmol/L. SPS (sodium polystyrene sulfonate) and patiromer showed smaller and delayed effects. Secondary Outcomes: Hypoglycemia occurred in 17% of insulin-treated patients. Dialysis was needed in 6.2%. Mortality rates were not significantly different among treatment groups. Substantial Clinical and Methodological Heterogeneity: One of the most important limitations of this SRMA was the considerable heterogeneity in study design, patient populations, baseline potassium levels, and definitions of hyperkalemia. For example, some studies included only CKD patients, while others focused on acutely ill hospitalized individuals or dialysis-dependent populations. Furthermore, the timing of outcome measurements varied, making direct comparisons difficult. This heterogeneity undermines the consistency of pooled estimates and limits the applicability of the findings to specific ED populations. Risk of Bias in Primary Studies: Many of the included trials had methodological weaknesses, including poor allocation concealment, lack of masking, and incomplete outcome data. Several studies did not clearly describe their randomization procedures. These issues increase the risk of performance and detection bias, especially when subjective outcomes or clinician decisions like the need for dialysis. The GRADE framework used by the authors appropriately rated much of the evidence as “low” or “very low” certainty for key comparisons. These biases raise doubts about the internal validity of the SRMA conclusions and highlight the need for better-quality trials in this domain. Co-Interventions and Protocol Variability: A recurring issue was the use of multiple simultaneous treatments across arms, such as combining insulin, beta-agonists, and calcium gluconate in varying doses and sequences. This practice, while clinically realistic and pragmatic, muddled the attribution of treatment effect to any single agent. In real-world ED settings, polytherapy is common, but in research, this confounds the estimation of the independent effectiveness of each drug. Without stratified analyses that control for such co-interventions, it is difficult to know whether observed reductions in potassium were due to one agent or the combination of agents. This limits the SRMA’s ability to inform what might be the best therapeutic option. Sample Sizes and Few Events: Despite including over 100 studies, many of the comparisons within the SRMA were based on small individual trials with limited numbers of participants and few outcome events. As an example, data on adverse effects like hypoglycemia or need for dialysis were inconsistently reported and often underpowered to detect differences. The lack of data leads to wide confidence intervals and imprecise point estimates, which weaken the clinical significance and reproducibility of the findings. Lack of Focus on ED-Specific Contexts: Though the SRMA is highly relevant to emergency medicine, only a minority of included studies were conducted in ED settings. Many trials were hospital-based or conducted in specialized units like nephrology wards, and some included stable outpatient populations. This matters because ED patients often present with more acute symptoms, comorbidities, and a need for rapid intervention. Additionally, drug availability and workflow constraints in the ED differ from other settings. Therefore, the external validity of the findings to ED practice is limited, and the SRMA may not fully capture the nuances of time-sensitive decision-making in the ED environment. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We agree with the authors’ conclusions but would emphasize the limited certainty and highlight the need for better patient-oriented outcome data before changing practice broadly.  SGEM Bottom Line: Insulin-glucose remains a reliable first-line agent for acute hyperkalemia management, but newer agents like sodium zirconium cyclosilicate show promise and may play a complementary role. Case Resolution: You administer 10 units of IV insulin with an amp of D50 and initiate inhaled albuterol. You consult nephrology and start sodium zirconium cyclosilicate, which is available in your ED. Repeat potassium at four hours drops to 5.4 mmol/L. No dialysis is needed. William Toon Clinical Application: This SRMA reaffirms insulin-glucose as the first-line treatment for hyperkalemia in the ED. It also supports adding beta-agonists when needed, de-emphasizing bicarbonate and sodium polystyrene sulfonate in acute settings, and suggests newer agents like SZC for future integration into your ED’s hyperkalemia protocol. However, it does not mean we should not use calcium gluconate or chloride in patients with hyperkalemia. These agents are not meant to lower potassium levels, and it would be inappropriate to have expected them to do so. The SRMA did not demonstrate a patient-oriented outcome (POO) of benefits. We should interpret the findings cautiously. The absence of evidence of benefit is not the same as evidence of no benefit. Therefore, calcium should not be abandoned for the acute treatment of hyperkalemia solely based on this SRMA.

Date: August 11, 2025 Dr. Gillian Schmitz Guest Skeptic: Dr. Gillian Schmitz is a board-certified Emergency Physician practicing at The Naval Medical Center in San Diego. She is also a former President of the American College of Emergency Physicians (ACEP). This SGEM Xtra is inspired by the 1992 film A League of Their Own. Unlike our previous pop culture references like Buffy the Vampire Slayer, Star Trek, Batman, Top Gun, Ted Lasso and Mission: Impossible, this story is based on real events. The All-American Girls Professional Baseball League (AAGPBL) was created in 1943 and lasted until 1954. This league gave over 600 women a chance to play pro baseball. For the SGEMers who may not have seen this movie, here is a summary. A League of Their Own (1992) is a sports drama directed by Penny Marshall that tells the fictionalized story of the real-life All-American Girls Professional Baseball League. It was formed during World War II when many male baseball players were serving overseas. The film follows sisters Dottie Hinson and Kit Keller as they join the Rockford Peaches and navigate the challenges of playing professional baseball in a male-dominated society. With a blend of humour, heart, and historical insight, the film highlights themes of gender roles, perseverance, and the lasting bonds formed through sport. Top 5 Themes from “A League of Their Own” As chosen and interpreted by Dr. Gillian Schmitz. Listen to the SEGM podcast to hear her full description of what the quotes mean to her. “I don’t have ball players. I have girls.” – Jimmy Dugan This quote reflects how society has historically minimized women’s capabilities in professional arenas. Emergency medicine, like baseball in the 1940s, has not always welcomed women without skepticism. Concerns about femininity, perception, and acceptance parallel the gender biases faced by women in emergency medicine leadership today. Even ‘proper’ women had concerns, expressing their worries about the ‘masculinization’ of these pioneer female athletes. Sound familiar? We have done several shows on the SGEM illustrating the gender inequity in the house of medicine. SGEM#352: Amendment – Addressing Gender Inequities in Academic Emergency Medicine SGEM Xtra: From EBM to FBM – Gender Equity in the House of Medicine SGEM Xtra: Unbreak My Heart – Women and Cardiovascular Disease SGEM#248: She Works Hard for the Money – Time’s Up in Healthcare SGEM Xtra: Money, Money, Money It’s A Rich Man’s World – In the House of Medicine SGEM Xtra: I’m in a FIX State of Mind “Why should you go? To say for once you actually did something… something special.” – Kit to Dottie This line speaks to the deep calling many women in emergency medicine feel. It reminds us of the early emergency medicine pioneers who were often told they were wasting their time. Yet they pressed forward, driven by the belief they could make a real difference. That passion to do something special, despite the challenges, still drives many of us in emergency medicine today. If you want to do something special, despite the challenge, then head over to FemInEM.org led by Drs. Dara Kass, Esther Choo, Jenny Beck-Esmay and the legend of emergency medicine, Dr. Diane Birnmaumer.  We also recently did an SGEM Xtra: This is My Fight Song - FeminEM 2.0. They are doing some amazing things, advancing gender equity in emergency medicine, improving reproductive healthcare delivery in emergency departments, mentorship and being champions of change. “You know, if I had your job, I’d kill myself.” – John Lovitz This moment of dry sarcasm reflects the burnout and emotional toll our specialty can bring. But it also highlights that, despite the difficulty, emergency medicine remains the best job in the world for many. I couldn’t imagine doing anything else. Emergency medicine still lights me up. “You gotta go where things happen.” – Marla’s Dad This is the heart of advocacy, leadership, and frontline emergency medicine. Whether it’s in the trauma bay or on Capitol Hill, women in emergency medicine are making things happen and often leading the way. You want to feel fulfilled? Go where things happen… or make them happen. “It’s supposed to be hard. If it wasn’t hard, everyone would do it. The hard is what makes it great.” – Jimmy Dugan This is the quintessential emergency medicine quote. The job is hard. The leadership path is hard. Breaking barriers is hard. But that’s what makes it great and worth doing. It’s that difficulty that shapes us, connects us, and gives meaning to what we do. Some final thoughts on the movie A League of Their Own? The movie reminds us that history is full of stories about women rising to the challenge, creating new paths, and demanding space at the table. Progress has been made, but there is still more work to be done. This includes representation in leadership and issues of gender pay gaps. There’s still much to challenge and change, but also much to celebrate. Emergency medicine has its league of extraordinary women, like Dr. Diane Birnbaumer, Dr. Judith Tintinalli, Dr. Dara Kass and many more. They continue to change the game, one shift, one policy, one pitch at a time. What pop culture topic with a strong female message should the SGEM cover next? Send an email to TheSGEM@gmail.com with “Xtra” in the subject line. Who knows, you might be a future guest skeptic on the SGEM. The SGEM will return to start Season#14 with a structured critical appraisal of a recent publication.  We will continue to strive to reduce the knowledge translation window from over ten years to less than one year, leveraging the power of social media. Our ultimate goal is for patients to get the best care, based on the best evidence. Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

Reference: Otterness et al. The Use of TENS for the Treatment of Back Pain in the Emergency Department: A Randomized Controlled Trial. AEM Aug 2025 Date: August 22, 2025 Guest Skeptic: Dr. Lauren Westafer is an Assistant Professor in the Department of Emergency Medicine at the University of Massachusetts Medical School, Baystate. She is the co-founder of FOAMcast and a researcher in pulmonary embolism and implementation science.  Dr. Westafer serves as the research methodology editor for Annals of Emergency Medicine. Case: A 44-year-old man presents to the emergency department (ED) with low back pain after bending to pick up his child. He has pain in his left lower back that is worse when he moves. He has no fever, chills, weakness, or numbness. He has well-controlled hypertension and no history of recent antibiotic use or drug use. The patient has no midline tenderness, is without neurological deficit, and has no red flag features on history and physical exam. He took 500 mg of acetaminophen a few times without significant relief. Background: Back pain is one of the most common reasons patients seek ED care, with an estimated 2.5 million ED visits for back pain each year. After dangerous diagnoses such as spinal epidural abscess, cord compression, and ruptured abdominal aortic aneurysm have been excluded, the next challenge for emergency clinicians is analgesia to improve the patient’s pain and mobility. Unfortunately, there are numerous causes of musculoskeletal low back pain, rendering a single treatment course inconsistently effective for all-comers. Many pharmacological and non-pharmacological therapies have been tried with limited efficacy.  Acetaminophen (Williams et al Lancet 2014) Muscle relaxants (Friedman et al JAMA 2015) NSAIDs (Machado et al Ann Rheum Dis 2017) Steroids (Balakrishnamoorthy et al Emerg Med J 2014) Benzodiazepines (Friedman et al Ann Emerg Med 2017) Cognitive Behavioral Therapy and mindfulness (Cherkin et al JAMA 2016) Chiropractic (Paige et al JAMA 2017) Physical therapy (Paolucci et al J Pain Research 2018) Acupuncture (Colquhoun and Novella Anesthesia and Analgesia 2013) One treatment that can be very effective but comes with very real potential harms is opioids. The American College of Emergency Physicians (ACEP) has addressed the issue of opioid use in patients being discharged home after an acute episode of pain. They give a Level C Recommendation saying: Do not routinely prescribe, or knowingly cause to be co-prescribed, a simultaneous course of opioids and benzodiazepines (as well as other muscle relaxants/sedative-hypnotics) for treatment of an acute episode of pain in patients discharged from the emergency department (Consensus recommendation).  Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological modality that administers low-intensity electrical stimulation to inhibit nociceptive pain signals. The efficacy of TENS devices in acute low back pain is uncertain. Clinical Question: Is transcutaneous electrical nerve stimulation (TENS) more effective at relieving back pain than sham TENS? Reference: Otterness et al. The Use of TENS for the Treatment of Back Pain in the Emergency Department: A Randomized Controlled Trial. AEM Aug 2025 Population: Adult ED patients (≥18 yr) with thoracic or lumbar back pain of at least moderate severity when research assistants were present (Mon–Fri, 8a–8p). Exclusions: Patients with suspected spinal cord injury or infectious etiology, fractures, hemodynamic instability, allergy to standard analgesics, pacemakers, and those with skin conditions precluding TENS application were excluded. Intervention: Two cutaneous TENS adhesive pads above and below the point of maximal tenderness with TENS unit set at a point just below the pain threshold and gradually increased for up to 30 minutes. Comparison: Sham TENS pads applied but no electrical current. Patients were told they might or might not feel pulses. Outcome: Primary Outcome: Absolute reduction in pain (0–10 NRS) from baseline to 30  Secondary Outcomes: Administration of rescue medications, change in pain severity, patient satisfaction with assigned treatment, and whether patients would recommend the same treatment Trial: Single-center randomized controlled trial Dr. Kara Otterness This is an SGEMHOP, and we are pleased to have the lead author on the episode, Dr. Kara Otterness. She is originally from Illinois and graduated from Drexel University College of Medicine and completed her Emergency Medicine residency training at NYU/Bellevue. She joined the Stony Brook EM faculty in 2015. She is passionate about teaching, medical education and currently serves as one of the assistant program directors at Stony Brook.  Dr. Otterness has been a guest skeptic on SGEM#96.  Authors’ Conclusions: “TENS was more effective than sham TENS at reducing pain severity in adult ED patients with back pain.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes 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). No  The patients in both groups were similar with respect to prognostic factors. Yes  All participants (patients, clinicians, outcome assessors) were unaware of group allocation. No 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. Unsure Financial conflicts of interest. None Results: The total cohort consisted of 80 patients. The mean age was 46 years. It was evenly split between female and male patients. The vast majority had lumbar pain (86%), 40% traumatic and 33% recurrent pain. Roughly half of patients had tried self-care with over-the-counter medications, and 31% had used heat.   Key Results: TENS produced a greater reduction in 30-minute pain than sham and reduced the need for rescue meds, with higher satisfaction and similar functional measures. Primary Outcome: The mean difference in change in pain scores was 1.2 (95% CI 0.5-1.9) p=0.002 Secondary Outcomes: Overall, secondary outcomes favoured the intervention. Rescue medications were administered to a higher proportion of patients in the sham TENS group (73% vs 45%), and more patients rated the degree of pain relief as better or much better in the TENS group (55% vs 26%). More patients in the intervention group were satisfied with their treatment (78% vs 50%). Listen to the SGEM podcast to hear Kara respond to our five nerdy points.  Convenience Sample: This trial used a convenience sample of patients enrolled only when research assistants were available (weekday business hours). Restricting recruitment in this way creates a risk of selection bias and limits generalizability because the study population may differ systematically from all ED back-pain patients. For example, patients who present to the ED at night and on weekends may have different injury mechanisms, comorbidities, pain severity or expectations. Compromised Masking: Although the trial was designed to be patient and assessor-mask, most patients correctly guessed their group allocation (95% TENS and 83% sham). When masking is not maintained, especially for subjective outcomes like pain scores, patients’ expectations can influence reported outcomes (placebo/nocebo effects). This can inflate the apparent benefit in the intervention arm, a form of differential measurement bias. True allocation concealment and maintaining blinding integrity are central to avoiding biased estimates of effect in RCTs. However, it is difficult to think about how such an intervention could be delivered without patients guessing correctly. Clinical vs Statistical Significance: The trial’s primary outcome did reach statistical significance (mean pain reduction difference 1.2 points, 95% CI 0.5–1.9) p =0.002. However, the effect size was close to or below many published minimum clinically important difference (MCID) thresholds for acute pain of around 1.5 on a 0–10 scale. Overemphasis on statistical significance without weighing clinical relevance can lead to the adoption of interventions that improve scores in a way that is detectable to researchers but not perceptible or valuable to patients. Small Sample Size: Patient recruitment in the ED is notoriously difficult due to difficulties staffing research staff at all hours of the day and during acute conditions. The authors recruited an adequate number of patients (n=80) for their power analysis; however, this resulted in large confidence intervals and ranges. Small studies are more vulnerable to random error and chance imbalances in prognostic factors, even with randomization. This increases the likelihood that the observed effect could be an overestimate (small-study effect) and reduces confidence in the precision of the result. Single-Centred: Because the trial was conducted in a single ED, the findings may not translate directly to other practice environments. Results from a tertiary academic centre (often with more resources, specialist staff, and research infrastructure) may not reflect community EDs, rural settings, or different health systems. Patient demographics, case mix, staff expertise, and even equipment quality can influence both the feasibility of the intervention and its observed effect. Without replication in multiple, diverse sites,

Reference:  Othman AA, et al. Combined ketamine and midazolam vs. midazolam alone for initial treatment of pediatric generalized convulsive status epilepticus (Ket-Mid study): A randomized controlled trial. Pediatric Neurology. June 2025 Date: May 27, 2025 Dr. James Chamberlain Guest Skeptic: Dr. James Chamberlain is a pediatric emergency medicine attending physician at Children’s National Hospital in Washington, DC where he is the Director of Data Analytics and Informatics for the Division of Emergency Medicine. He is also a Professor of Emergency Medicine and Pediatrics at George Washington School of Medicine and Health Sciences. He has led or co-led two large national trials of status epilepticus and is starting a third, the Ketamine adjuvant for Established Status Epilepticus Treatment Trial (KESETT). Case: A two-year-old boy with a known seizure disorder is brought to the emergency department (ED) by his family for a seizure at home. The episode is described as generalized tonic-clonic activity which self-resolved after about a minute. He was post-ictal afterwards and has not fully returned to baseline. He has not had any recent fevers or illnesses. During your conversation with his parents, he starts seizing again. You administer two doses of a benzodiazepine, but the seizure continues. You give an additional levetiracetam load, which stops the seizure activity, and he is admitted to the hospital for observation. Afterwards, a medical trainee you are working with says to you, “I read that there’s been interest in other medications like ketamine in the treatment of seizures. Do you think there would have been any benefit in giving ketamine earlier?” Background: We often see children presenting with seizures in the ED. Currently, the standard of care recommends the use of benzodiazepines such as midazolam as first-line treatment. Midazolam, but not the other benzodiazepines, can be given intravenously, intramuscularly, intranasally, or as a buccal paste. Sometimes this works and stops the seizure activity. Sometimes it does not. Seizures that are refractory to treatment are dangerous and can lead to neuronal injury, long-term deficits, or even death. We want to stop seizure activity as quickly as we can. The typical management of seizures is to give a benzodiapene. If that does not work, give a second dose. If that still doesn't stop the seizure, then administer another anti-seizure medication like levetiracetam, fosphenytoin, or valproate. There’s been increasing interest in the use of ketamine for seizures. There are several factors that make ketamine potentially a very powerful drug for status epilepticus. Ketamine is an NMDA receptor antagonist and therefore theoretically should break the vicious cycle of status. There have been dozens of animal studies in at least 4 different species demonstrating efficacy as early treatment of status. In some of these studies, ketamine and other NMDA receptor antagonists are neuroprotective. In humans, ketamine is widely used for super refractory status, when all other medications have failed. Estimates are that it is about 70% effective for this indication. We have a long track record of using ketamine safely in the emergency department setting and growing experience in EMS. Ketamine is well tolerated, short-acting, and preserves protective airway reflexes and ventilation. Even very large accidental overdoses have been well tolerated. The one caveat is that we don’t know if all these safety parameters hold in the condition of status epilepticus, but limited case series have not shown safety problems. Currently, it is not part of conventional therapy for pediatric status epilepticus, but there is thought that it may work synergistically with benzodiazepines in stopping seizures. Clinical Question: Is ketamine combined with midazolam more effective than midazolam alone in the treatment of pediatric generalized convulsive status epilepticus? Reference:  Othman AA, et al. Combined ketamine and midazolam vs. midazolam alone for initial treatment of pediatric generalized convulsive status epilepticus (Ket-Mid study): A randomized controlled trial. Pediatric Neurology. June 2025 Population: Children 6 months to 16 years presenting with generalized convulsive status epilepticus without prior treatment with antiseizure medications (ASMs) for the current episode. This was defined as clinically detectable generalized tonic-clonic convulsions that persist or recur without regaining consciousness in between for longer than 5 minutes. Exclusions: Previous treatment with ASM, traumatic brain injury (TBI), conditions associated with increased intracranial pressure, hypertension, glaucoma, hyperthyroidism, pheochromocytoma, end-stage kidney or liver disease, cardiac disease, history of alcohol intake, hypoglycemia, hyperglycemia, inborn errors of metabolism, known allergy or contraindication to study drugs, known or suspected psychiatric disorder, failure to get IV access in first 5 minutes of stabilization, cessation of seizures within the first 5 minutes, and failure to obtain informed consent. Intervention: IV ketamine (2 mg/kg) plus IV midazolam (0.2 mg/kg) Comparison: IV placebo plus IV midazolam Outcome: Primary: Cessation of clinical seizures at 5 minutes post-drug administration Secondary: Need for repeat midazolam during the first 15 minutes of study timeframe, seizure cessation at 15, 35, and 55 minutes, seizure control, adverse events (hypotension, hypertension, arrhythmia, emergence phenomenon, rash), need for intubation, and mortality. Type of Study: Randomized, two-group, parallel, 1:1 superiority, double-masked, placebo-controlled trial Authors’ Conclusions: “Ketamine-midazolam combination may be more effective than midazolam alone for the initial treatment of pediatric GCSE, but this should be confirmed in future research.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Yes 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. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes 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. Yes Financial conflicts of interest. No financial conflicts of interest Results: They included 144 children. Half were assigned to the ketamine and midazolam group, and the other half were assigned to the placebo and midazolam group. The most common causes of generalized convulsive status epilepticus include febrile seizures and known epilepsy. Eleven percent had a CNS infection, and four percent had other or unknown etiologies. Key Results: The combination of ketamine and midazolam was superior to midazolam alone in treating children with generalized convulsive status epilepticus. Primary Outcome:  In the combined ketamine and midazolam group, 76.4% of patients had cessation of seizure activity compared to 20.8% of the patients who only received midazolam. Risk Ratio (RR) 3.7 (95% CI: 2.3 to 5.9, p< 0.001) Secondary Outcomes:   The ketamine and midazolam group also had higher percentages of seizure cessation at 15, 35, and 55 minutes. The ketamine and midazolam group had lower percentages of requiring repeat midazolam (23.6% vs 79.3%) or endotracheal intubation (4.2% vs 20.8%). Selection Bias The authors screened 251 patients for eligibility. They excluded around 40% because they didn't meet the inclusion criteria. There was a long list of exclusion criteria. While some of the conditions they excluded could be determined quickly, there are others listed, such as conditions associated with increased intracranial pressure, hyperthyroidism, pheochromocytoma, inborn errors of metabolism, and known or suspected psychiatric disorders that need some time to work up. We’re not sure how they were able to make determinations of all of those potential medical problems before enrollment. This may lead to a selection bias. Primary Outcome Their primary outcome was the cessation of clinical seizure activity, but what about subclinical seizures? One of the challenges in the ED of treating seizures is that we can give medications that stop the clinical seizure activity we can see. Afterwards, when the patient has stopped clinically seizing but is sleepy and has not returned to baseline, we have to try and figure out if they are still not back and baseline because they are post-ictal, sedated from all of the seizure medications, or subclinically seizing. Fortunately, subclinical status is less common in children. It is possible they missed subclinical seizures in this trial, which are important to recognize and treat. From an evidence-based medicine perspective, valid outcome measures are those that are objective, reliably assessed, and aligned with patient-important endpoints. EEG serves as a critical tool to meet these standards in the context of seizure management. Unfortunately, its absence in this trial limits the internal validity and the generalizability to other centers where EEG is routinely used in managing status epilepticus. Future and ongoing studies of status epilepticus in the United States will require placement of a rapid EEG to obviate this ascertainment bias and improves the rigor of the outcome assessment,