The Skeptics Guide to Emergency Medicine

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The Skeptics Guide to Emergency Medicine is a education podcast hosted by Dr. Ken Milne, with 300 episodes on record and a Required Pod Score of 80. PitchCentric scores this show on Booking Probability, Listen Score, and live audience signals refreshed every 24 hours.

Dr. Ken Milne hosts The Skeptics Guide to Emergency Medicine, a education show with 300 episodes published.

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  The Skeptics Guide to Emergency Medicine

  SGEM#517 : I Will Try to Fix You. Surgery or Not for Pediatric Displaced Medial Epicondyle Elbow Fractures

  Aug 8, 202649 min

  Reference: Perry DC, et al. Surgical fixation versus non-surgical care for children with a displaced medial epicondyle fracture of the elbow (the SCIENCE study): a multicentre, randomised controlled, superiority trial and economic evaluation. The Lancet 2026 Date: July 14, 2026 Guest Skeptics: Dr. Megan Terle is an orthopedic surgeon and Assistant Professor for Pediatrics and Trauma services at UC Davis Health. She completed her orthopedics residency at the University of Washington and completed two fellowships, one in pediatrics at the University of Washington and one in trauma at UC Davis. Dr. Megan Terle Dr. Holly Leshikar is also an orthopedic surgeon and Associate Professor for Pediatrics and Trauma services at UC Davis Health. She completed orthopedics residency at UC Davis and a pediatric orthopedic surgery fellowship at Vanderbilt Children’s Hospital in Nashville. Case: An 11-year-old gymnast comes to the emergency department (ED) after a fall from the bars. She felt a “pop” in the elbow and now refuses to move the arm. The elbow is swollen and tender on your examination. You perform a careful neurovascular exam and note intact distal perfusion and no neurological deficits. You temporarily immobilize the arm and order radiographs. X-ray shows a displaced medial epicondyle fracture. Her parent asks you: “Does she need surgery to put the bone back where it belongs?” Dr. Holly Leshikar Background: Medial epicondyle fractures are pediatric elbow injuries involving the bony prominence on the inside of the distal humerus. In children, this area is a secondary growth center. The typical mechanism is an avulsion injury from valgus stress at the elbow, often after a fall onto an outstretched hand or a sports-related injury. These fractures are extra-articular in most cases, but they can be associated with elbow dislocation and, occasionally, the fragment can become trapped inside the joint. Key early priorities are pain control, neurovascular assessment, recognition and reduction of any elbow dislocation, and post-reduction imaging to ensure the medial epicondyle fragment is not incarcerated in the joint. Management has traditionally varied widely. Minimally displaced fractures are usually treated non-operatively with immobilization, often in an above-elbow backslab or cast with the elbow flexed around 900. Surgery, usually open reduction and internal fixation (ORIF) with a screw or wires, has generally been reserved for clearer indications such as an incarcerated fragment, open fracture, ulnar nerve entrapment, gross elbow instability, or selected high-demand upper extremity athletes. The real controversy has been the isolated displaced fracture. Supporters of ORIF argue that surgery restores anatomy, improves the reliability of healing, improves stability, and speeds return to activity. Observational studies have supported both approaches, driving uncertainty. Pediatric orthopedics has historically had few clinical trials, leaving decisions shaped by tradition, expert opinion, and retrospective data. Much of the older literature on the medial epicondyle has methodological limitations (e.g., follow-up issues, selection bias, limited patient-reported outcomes). One smaller RCT from Finland (n=72) suggested non-operative care was non-inferior at 1 year, but a single small trial still left uncertainty. Clinical Question: In children (age 7 to 15 years) with a displaced medial epicondyle fracture, does surgical fixation improve patient-important outcomes compared with non-surgical immobilization, and is it cost-effective? Reference: Perry DC, et al. Surgical fixation versus non-surgical care for children with a displaced medial epicondyle fracture of the elbow (the SCIENCE study): a multicentre, randomised controlled, superiority trial and economic evaluation. The Lancet 2026 This was the same lead author as the FORCE trial covered in SGEM #372 that taught us it is reasonable to treat a buckle fracture of the forearm with a soft bandage and the CRAFFT trial covered in SGEM #510 that taught us a cast-first strategy for young children with displaced distal radius fractures can be a reasonable approach. Population: Children 7 to 15 years of age with a displaced medial epicondyle fracture (across 59 hospitals in the UK/Australia/NZ) Exclusion: Injury >2 weeks old; incarcerated fragment in joint; complex intra-articular elbow fracture; additional fractures outside the elbow. Intervention: Surgical fixation under general anaesthesia and fixation with screws/wires. A cast, splint, or bandage was applied afterward, and the duration was at the surgeon's discretion. Comparison: Non-surgical care which was immobilization of the elbow elbow ~90° flexion with cast/splint/sling. Duration was at the discretion of the surgeon. They were also allowed mobilization under clinical supervision and as tolerated base don pain. Casting >4 weeks was discouraged. Outcome: Primary Outcome: Functional recovery assessed by the Patient Report Outcomes Measurement System (PROMIS) Upper Extremity Score for Children Computer Adaptive Test (CAT) at 12 months. A higher score means better limb function. Secondary Outcomes: Sports and performing arts participation assessed with the Disability of the Arm Shoulder, and Hand (DASH), pain assessment with the Wong-Baker Faces Pain Scale, health-related quality of life assessed with EQ-5D-Y, complications, health-care utilization, parental leave, days of purchased childcare, school absence Trial: multicentre, randomised controlled superiority trial Authors’ Conclusions: “The SCIENCE trial demonstrates that surgical fixation offers no clinical benefit and is not cost-effective compared with non-surgical care, while exposing children to avoidable surgical risks. These findings suggest that non-surgical care should be adopted as the default management strategy for these injuries, regardless of initial elbow dislocation status.” 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. No Trial Funding. Funded by the National Institute for Health and Care Research Health Technology Assessment programme, with additional NIHR Academy, Oxford NIHR Biomedical Research Centre, and Starship Foundation support. Financial conflicts of interest. Declared NIHR grant support; DCP and MLC had NIHR HTA roles; KW reported Zimmer Biomet and Medartis fellowship support; JGW reported other grants and consultancy fees. Results: A total of 647 patients were assessed for eligibility, with 335 being randomized, and 334 were included in the ITT analysis. There were 166 children assigned to non-surgical care and 168 assigned to surgical fixation. Mean age was 11.7 years, 51% were female, 58% of injuries were sports-related, and 24% presented with elbow dislocation. The dominant arm was injured in 51% of participants. Primary Outcome: (PROMIS UE at 12 months) The non-surgical group had a score of 53.1 (SD 7.8), while the surgical group had a score of 54.3 (SD 5.7). This was a mean difference of 1.57 (95% CI –0.01 to 3.14), p=0.052 The pre-specified clinically important difference was 4 points, so the observed difference was not clinically meaningful. There was a slight difference in the per-protocol analysis. Non-surgical group had a score of 53 (SD 7.9). The surgical group had a score of 54.5 (SD 5.6). There was a mean difference of 1.76 (95% CI 0.1 to 3.42), p=0.0372 There was not much difference in the PROMIS scores as they tracked the patients over time. There was improvement in the scores up until around 6 months and the scores started to plateau. Secondary Outcomes: There were many secondary outcomes. We will highlight a few. They used different tools like the DASH, Wong-Baker Faces Pain Scale, or the EQ-5D-Y to measure return to activity, pain, and quality of life between the two groups. There were no significant differences between the two groups. There was less school absence in the non-surgical group (5 vs 3.1 days) with a mean difference of 2.2 days (95% CI 0.7-3.6), p=0.003. That’s important to me as a parent. Among the 150 children who underwent surgical management, 14 (9%) had intraoperative complications that included ulnar nerve injuries, hardware issues, fragmentation of the bony fragment. Seven required more surgery afterwards for these complications, and another 17 required surgery for screw or wire removal. There were 5 (2%) complications in the 184 children who underwent non-surgical management, with one having a complication related to the cast and 3 who had to undergo delayed fixation of the bone fragments. The surgical treatment option was also more expensive with a mean additional cost of £2435 per patient (95% CI; £1812 to £3057). We want to give a shout-out to the involvement of patients and the public in many aspects of the study. The authors report that patients and the public were involved in design, conduct, oversight and dissemination. They helped select the outcomes that mattered the most and defined what constituted a “meaningful” treatment effect....

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  The Skeptics Guide to Emergency Medicine

  SGEM#516: A Whole Lotta Blood – Whole Blood Transfusion in the Prehospital Setting

  Aug 1, 202640 min

  Date: July 27, 2026 2026 Guest Skeptic: Dr. Howard (Howie) Mel is an emergency physician and FACEP. Reference: Smith JE et al. SWiFT Trial Group. Prehospital Whole Blood in Traumatic Hemorrhage - a Randomized Controlled Trial. NEJM 2026 March Case: A 36-year-old man is brought to the emergency department (ED) by air ambulance after a high-speed motorcycle crash. Paramedics report blunt polytrauma, transient hypotension, tachycardia, pelvic instability, and concern for intra-abdominal bleeding. IV/IO access was obtained in the field, and prehospital blood was started. On arrival, he is pale, cool, and diaphoretic, with blood pressure (BP) 86/52 mm Hg, heart rate (HR) 128 bpm, Glasgow Coma Scale (GCS) score of 13, a pelvic binder in place, abdominal distension, and a positive FAST. Background: Traumatic hemorrhage is one of the classic time-critical problems in emergency care. Patients do not die because their hemoglobin is low on tomorrow’s CBC; they die because they are bleeding now. This is one of the reasons the 11th edition of ATLS has formally prioritized external bleeding before airway management (SGEM Xtra). The new mnemonic is xABCDE, with the “x” standing for exsanguinating hemorrhage. This reinforces early tourniquet use, direct pressure, and hemostatic adjuncts as first-line priorities when appropriate. For in-hospital-based trauma resuscitation, the PROPPR trial helped move the conversation toward balanced component therapy. In that 2015 RCT, they compared 1:1:1 plasma:platelets:red cells with 1:1:2. The authors showed better secondary outcomes (hemostasis and fewer deaths from exsanguination at 24 hours), even though the primary outcome (overall mortality) was not statistically different (SGEM#109). The harder question is what should happen before the patient ever reaches the trauma bay. Prehospital transfusion sounds attractive because it shortens the time to blood-based resuscitation, but the evidence has been mixed. The PAMPer study found lower 30-day mortality with prehospital plasma in patients at risk for hemorrhagic shock transported by air, while RePHILL did not show superiority for a prehospital blood-product strategy over saline (SGEM#369). A pooled post hoc analysis of PAMPer and COMBAT suggested that any benefit from prehospital plasma may be most apparent when transport times are longer, and resuscitation is started early enough to matter. For emergency clinicians, the real debate is not whether bleeding trauma patients need blood. They do. The more useful question is which product, for which patient, in which system, and over what transport interval. That is why prehospital transfusion research keeps circling back to logistics, case selection, transport time, and whether a prehospital strategy complements what happens after ED arrival rather than simply adding complexity. Clinical Question: In trauma patients with life-threatening hemorrhage treated by participating air ambulance services, does prehospital transfusion with up to 2 units of leukocyte-depleted whole blood, compared with standard component therapy (up to 2 units of red cells and 2 units of plasma), reduce the composite of death or massive transfusion within 24 hours? Reference: Smith JE et al. SWiFT Trial Group. Prehospital Whole Blood in Traumatic Hemorrhage - a Randomized Controlled Trial. NEJM 2026 March Population: Patients of any age with traumatic injury, attended by a participating air ambulance service clinical team, who required prehospital blood transfusion for major traumatic hemorrhage. Exclusions: Patients were excluded if IV or IO access could not be established, if there was a known objection to blood transfusion, or if blood products had already been given before the participating air ambulance service arrived. For the main modified intention-to-treat analysis, nontraumatic hemorrhage and traumatic cardiac arrest on arrival of the air ambulance were excluded. Intervention: Up to 2 units of prehospital leukocyte-depleted whole blood. Comparison: Up to 2 units of red blood cells and 2 units of plasma (thawed fresh frozen plasma or lyophilized plasma, depending on service). Outcomes: Primary Outcome: Composite of death from any cause or massive transfusion within 24 hours after randomization. Massive transfusion was defined as at least 10 units of blood components/products in adults, and at least 40 mL/kg in pediatric participants under 16 years weighing under 50 kg. Secondary outcomes: All-cause mortality at 6 hours, 24 hours, 30 days, and 90 days; massive transfusion; organ-failure–free days up to 30 days; days in critical care and acute care hospital; units of blood products received in 24 hours; cell salvage; additional hemostatic agents; coagulopathy; acid-base disturbance; thrombotic events; transfusion reactions/events; and planned cost-effectiveness and quality-of-life analyses. Type of Study: Pragmatic, multicenter, parallel-group, open-label (unblinded), superiority randomized controlled trial (RCT). Authors’ Conclusions: “Among participants with life-threatening hemorrhage, prehospital transfusion of 2 units of whole blood was not superior to standard care in reducing the risk of death or massive transfusion within 24 hours.” Quality Checklist for Randomized Clinical Trials: Did the study population include or focus on those in the emergency department? No Were the patients adequately randomized? Yes Was the randomization process concealed? Yes Were the patients analyzed in the groups to which they were randomized (i.e. intention-to-treat analysis)? No Were the patients recruited consecutively (i.e. no selection bias)? Unsure Were both groups similar with respect to prognostic factors? Yes Were all participants (patients, clinicians, outcome assessors) unaware of group allocation (blinded/masked)? No Were all groups treated equally except for the intervention? Unsure Was the follow-up complete (i.e. at least 80% for both groups)? Yes Were all patient-important outcomes considered? Unsure Was the treatment effect large enough and precise enough to be clinically significant? No Who funded the trial? NHS Blood and Transplant, participating Air Ambulance Charities, and the Ministry of Defence. The sponsor was NHS Blood and Transplant. Did the authors declare any conflicts of interest? Unsure from the main paper files alone, but the protocol states that at the time it was written, the chief investigators, principal investigators, and trial committees had no competing interests, with a plan for disclosure of any arising conflicts during the trial. Results: A total of 942 patients were randomized overall. After exclusions and data removal, 641 participants comprised the modified intention-to-treat population (327 whole blood, 314 standard care). The primary outcome analysis used complete cases: 314 in the whole-blood group and 302 in the standard-care group. Most participants were male (76%), the majority had blunt trauma (71%), and the median age was 38 years in the whole-blood group and 35 years in the standard-care group. Key Result: Prehospital transfusion with up to 2 units of whole blood was not superior to standard component therapy for reducing 24-hour death or massive transfusion in patients with life-threatening traumatic hemorrhage. Primary Outcome: Occurred in 153/314 (48.7%) in the whole-blood group and 144/302 (47.7%) in the standard-care group, for a relative risk of 1.02 (95% CI 0.80 to 1.31; P=0.84). Secondary Outcomes: Mortality at 6 hours, 24 hours, 30 days, and 90 days appeared similar between groups, as did the rate of massive transfusion and most other secondary outcomes. One notable difference was that prothrombin time above the normal range was more common in the whole-blood group (40.7% vs 30.5%; RR 1.31, 95% CI 1.10 to 1.56). Serious adverse events were slightly fewer with whole blood (31 vs 37), thrombotic events appeared similar, and two transfusion-related/SHOT-type events occurred in standard care with none reported in whole blood. 1. Modified ITT Analysis (mITT): In SWiFT, the main analysis was modified intention-to-treat, excluding nontraumatic hemorrhage, traumatic cardiac arrest on arrival, and patients whose data were withdrawn or deleted after a serious protocol breach. On top of that, the primary analysis was effectively a complete-case analysis within the modified ITT population. Some of these exclusions were clinically reasonable, but they still weaken the integrity of randomization and raise the possibility that excluded participants differed in important ways from included participants. Open Label 2. Open label: This was an unmasked trial once the box was opened. Death is a hard outcome, but “massive transfusion” is not purely biological; it is somewhat subjective and depends partly on clinician decisions, local transfusion behaviour, and downstream management. That makes the composite more vulnerable to performance bias than a purely objective endpoint, such as mortality alone. 3. Contamination & Protocol Slippage: A clean superiority trial needs meaningful separation between groups. In SWiFT, protocol deviations occurred in roughly 7% of both groups, randomization errors occurred in about 5%, and 7 participants in the standard-care arm received whole blood prehospital due to mispacked boxes or because only whole-blood boxes were available. There was also co-enrollment in other studies, including some deemed non-permissible. None of this invalidates the study outright, but it can dilute differences between groups and make a truly superior intervention harder to detect. 4. Lack of Power: The trial was powered for the primary composite, not for most secondary outcomes. Meanwhile, missingness was modest for the primary outcome but substantial for some secondary and safety measures: 90-day vital

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  The Skeptics Guide to Emergency Medicine

  SGEM Xtra: Ferraris, Friends, and First Responders – Lessons Learned from Watching Magnum, P.I.

  Jul 25, 202623 min

  Date: July 9, 2026 Guest Skeptic: Dr. Aaron Skolnik is an Assistant Professor of Emergency Medicine at the Mayo Clinic Alix School of Medicine and Vice Chair of Critical Care Medicine at Mayo Clinic Arizona. Aaron is a full-time multidisciplinary intensivist and is the medical student clerkship director for critical care. Today’s episode is a little different. We’re diving into a classic 80s TV show. Aaron and I were in Hawaii earlier this year at the Center for Continuing Medical Education Emergency Medicine and Acute Care Course. While walking down the beach, Aaron told me how much he loved Magnum PI. That made me think we should do an SGEM Xtra. We’ve done this before on the SGEM, using pop culture TV to reflect on medicine from Star Trek to Ted Lasso and, most recently, Buffy the Vampire Slayer. It turns out TV can be surprisingly educational. And today we’re going with Magnum, P.I. Magnum, P.I. aired from 1980 to 1988 and followed Thomas Magnum, a private investigator living in Hawaii. Alongside his Vietnam War friends, T.C. (helicopter pilot) and Rick (club owner). Magnum solves cases while constantly sparring with Higgins, the estate manager. But beneath the action and humour are themes that surprisingly resonate with emergency medicine. Five Lessons from Magnum, P.I. for Emergency Medicine 1. Teamwork is Everything Magnum never works alone. His success depends on his team. T.C. provides logistics, transport, and perspective. Rick is communication, connections and social intelligence. Higgins offers structure (even if annoying). EM Parallel: Emergency medicine is a team sport: Nurses, RTs, techs, EMS, and consultants are all critical High-performing teams outperform individual brilliance We should all be on Team Patient Takeaway: No matter how skilled you are, patient outcomes depend on the team. 2. The Hidden Burden: Post-Traumatic Stress Disorder and Mental Health Magnum and his friends carry emotional scars from Vietnam, which are often subtly portrayed but always present. EM Parallel: Exposure to trauma, moral injury and burnout, and high rates of PTSD among emergency clinicians Takeaway: Recognize it. Talk about it. Support each other. Mental health is not optional in EM. 3. We Love Our Toys and Should Use Them Wisely Magnum has a Ferrari 308 GTS, helicopter access and high-tech (for the time) surveillance equipment. EM Equivalent: Point-of-care ultrasound, video laryngoscopy, REBOA, and ECMO Takeaway: Technology is powerful, but tools don’t replace clinical reasoning. Use them appropriately, not reflexively. 4. Navigating “Higgins” (a.k.a. The Hospital Administrator) Magnum constantly clashes with Higgins over rules vs. reality. EM Parallel: Policies vs. patient care. Throughput pressures vs. quality. Documentation vs. bedside time. Takeaway: You must learn to work within the system, and occasionally around it, while advocating for patients. 5. Controlled Chaos: Comfort with Uncertainty Magnum thrives in unpredictable, evolving situations. He needs to act on incomplete information and changing circumstances, and make rapid decisions. EM Parallel: We have undifferentiated patients with diagnostic uncertainty and need to make time-sensitive decisions. Takeaway: Emergency medicine is about making the best possible decision with imperfect information, not waiting for certainty. SGEM Xtra Magnum P.I. Summary: Teamwork is greater than individual heroics Mental health matters Technology is a tool, not a crutch Systems navigation is part of the job Comfort with uncertainty is a core EM skill The SGEM will be back next episode with a structured critical appraisal of a recent publication. Trying to cut the knowledge translation window from over ten years to less than one with the power of social media. Remember to be skeptical of anything you learn, even if you learned it on the Skeptics’ Guide to Emergency Medicine.

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  The Skeptics Guide to Emergency Medicine

  SGEM#515: Now the Azithromycin Don’t Work for Preschool Wheeze

  Jul 18, 202625 min

  Reference: Denninghoff KR et al. Azithromycin for Preschoolers with Wheezing in the Emergency Department. New England Journal of Medicine. May 2026 Date: July 14, 2026 Dr. Zara Ibrahim Guest Skeptic: Dr. Zara Ibrahim is a pediatric emergency medicine fellow at Children’s National Hospital in Washington DC where she also completed medical school, pediatric residency. Her research interests include AI applications in medicine and health equity. In her time off, Zara likes to read books, travel, go on long walks to explore DC's excellent bakery scene, and do HIIT workouts to balance out the pastries. Case: A 3-year-old with a history of recurrent wheezing presents to the pediatric emergency department (ED) with cough, rhinorrhea, increased work of breathing, and expiratory wheeze. His Pediatric Respiratory Assessment Measure (PRAM) score is 6. He receives albuterol, ipratropium, and dexamethasone with some improvement. His parents ask: “Last time he was sick, someone gave him antibiotics, I think it was ‘Zith something. Would antibiotics help him get better faster?” Background: Preschool wheeze is best viewed as a heterogeneous clinical syndrome rather than a single diagnosis. Some of these children wheeze mainly during viral illnesses, some may be manifesting an early asthma phenotype, and a smaller number have alternative causes such as bronchiolitis, foreign-body aspiration, anatomic airway abnormalities, etc. Wheezing and asthma exacerbations are frequent reasons for ED care and hospitalization in children. In U.S. data from 2012 to 2020, asthma hospitalization rates were consistently highest among children aged 0 to 4 years and decreased across successive pediatric age groups. During an acute asthma-like episode, airway inflammation, mucosal edema, mucus hypersecretion, and bronchial smooth-muscle constriction further narrow the airways. This can produce expiratory wheeze, prolonged expiration, tachypnea, retractions, reduced air entry, and, in more severe episodes, hypoxemia. Viral respiratory infections are the most common triggers of acute wheezing and asthma exacerbations in young children, with rhinovirus and respiratory syncytial virus among the frequently identified pathogens. Because preschool children can’t typically perform reproducible spirometry, emergency clinicians rely on clinical examination, pulse oximetry, and validated bedside severity scores such as the Pediatric Respiratory Assessment Measure, or PRAM. The PRAM is a bedside score from 0 to 12 based on oxygen saturation, suprasternal retractions, scalene-muscle contraction, air entry, and wheezing; higher scores indicate greater severity. The immediate ED goal is to rapidly assess exacerbation severity, identify impending respiratory failure, and reassess the child’s response to treatment, rather than assign a permanent diagnostic label during a single acute visit. Standard management includes inhaled short-acting beta₂-agonists, early systemic glucocorticoids for moderate-to-severe exacerbations when appropriate, supplemental oxygen for hypoxemia, and repeated clinical assessment. Antibiotics are not routinely recommended for an asthma-like exacerbation unless there is a separate bacterial indication. Two biologically plausible arguments have been advanced in support of azithromycin. First, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae are often detected in the upper airways of young children, and observational studies have associated colonization or microbiome profiles dominated by these organisms with more severe lower respiratory illness and later recurrent wheeze or asthma. These associations raised the hypothesis that bacteria may contribute to some episodes, but nasopharyngeal detection can represent colonization and, by itself, does not establish lower-airway bacterial infection or causation. Second, macrolides have immunomodulatory and anti-inflammatory actions distinct from their antibacterial activity. Earlier outpatient randomized trials in selected children suggested that azithromycin, particularly when started very early in a respiratory illness before substantial airway obstruction developed, might shorten episodes or reduce progression to severe lower respiratory illness. In contrast, an earlier ED-based placebo-controlled trial found no reduction in symptom duration, short-acting beta₂-agonist use, or time to the next exacerbation. These mixed findings raised an important timing-and-severity question: might azithromycin have a pre-emptive effect early in an illness but little or no effect once moderate-to-severe wheezing is established? Clinical Question: In preschool children presenting to the ED with moderate-to-severe wheezing, does a 5-day course of azithromycin reduce wheezing-related symptom severity compared with placebo? Population: Children 18 to 59 months old presenting to one of eight PECARN-affiliated pediatric EDs with moderate-to-severe expiratory wheezing, defined as PRAM score ≥4 Excluded: Children with antibiotics in the prior two weeks, acute infection requiring systemic antibiotics, recent systemic glucocorticoids for wheezing, suspected foreign-body aspiration, prematurity, systemic illness other than allergies, azithromycin allergy, or active COVID-19. Intervention: Azithromycin 12 mg/kg orally once daily for 5 days. Comparison: Matching placebo for 5 days Outcome: Primary Outcome: Sum of Asthma Flare-up Diary for Young Children scores over 5 days. Scores ranged from 5 to 35, with higher scores indicating worse symptoms. Secondary Outcomes: ED length of stay, hospital length of stay, return ED visits or hospitalization within 72 hours, bacterial clearance, antimicrobial resistance, and adverse events. Type of Study: A multicentre, parallel-group, masked, placebo-controlled superiority randomized controlled trial. Authors’ Conclusions: “Azithromycin did not lead to a greater reduction in the severity of wheezing-related symptoms than placebo in preschool-age children who presented to the emergency department with moderate-to-severe acute wheezing.” 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. 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. No Financial conflicts of interest. The study was funded by NHLBI/NIH and PECARN, and the funders reportedly had no role in design, analysis, interpretation, manuscript writing, or publication decisions. Results: A total of 840 children were randomized. Of these, 521 (62%) tested positive for at least one of the three pathogenic bacteria, and 312 tested negative. Around half of the patients were hospitalized. The trial was stopped early for futility after an interim analysis Key Results: Adding five days of azithromycin to standard ED treatment did not reduce wheezing-related symptom severity compared with placebo. Primary Outcome: ADYC Symptoms Score There was no significant improvement in wheezing-related symptom severity with azithromycin, whether children had the prespecified bacteria detected or not. Secondary Outcomes: No meaningful differences were seen in ED length of stay, hospital length of stay, or 72-hour return ED visits/hospitalizations. Bacterial Clearance: Among bacteria-positive children with follow-up testing, azithromycin cleared the prespecified bacteria more often than placebo: 58.7% vs 11.4%. Adverse Events and Resistance: Adverse events were similar between groups, and no deaths occurred. Antimicrobial resistance at follow-up was similar among those who returned for follow-up testing, but the bacterial follow-up sample was incomplete Negative Study: This was a negative study. This is important because we know there is publication bias, where studies with positive or exciting findings are more likely to be submitted, accepted, published, promoted, and remembered. Negative trials can quietly disappear, leaving clinicians with an inflated sense that an intervention works. A well-done negative trial can be just as valuable as a positive one because it helps us stop doing things that do not help patients. Selection Bias/Generalizability: The flow diagram in Figure 1 provides food for thought. More than 2,600 children were eligible, but only 840 underwent randomization. Among families approached, about 64% declined to consent. In addition, some eligible families were never approached because of staffing, guardian availability, language, or administrative issues. This also included a small group where the provider had a clinical preference. This introduces selection bias. The children enrolled in the trial may not perfectly represent all preschoolers with wheezing who show up to the ED. For example, we do not know whether families who declined had strong feelings about antibiotics. Did some parents want azithromycin and not want to risk placebo? Did some parents want to avoid antibiotics and not want to risk receiving azithromycin? Were some families too stressed, too busy, or too overwhelmed to consider research participation? We do not know. The same question applies to clinicians....

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  The Skeptics Guide to Emergency Medicine

  SGEM#514: Every Time You Go Away (and survive alive for 90 days) – Is It Due To A Restricted Fluid Strategy with Early Vasopressors?

  Jul 11, 202632 min

  Date: July 9, 2026 Reference: The ARISE FLUIDS Investigators. Vasopressors or Fluids in Early Septic Shock. NEJM June 2026. Guest Skeptic: Dr. Aaron Skolnik is an Assistant Professor of Emergency Medicine at the Mayo Clinic Alix School of Medicine and Vice Chair of Critical Care Medicine at Mayo Clinic Arizona. He is board-certified in Emergency Medicine, Medical Toxicology, Addiction Medicine, Internal Medicine-Critical Care, and Neurocritical Care. Aaron is a full-time multidisciplinary intensivist and enjoys serving as the medical student clerkship director for critical care. Case: A 69-year-old man presents by EMS to the emergency department (ED) with fever, productive cough, confusion, and weakness. He has hypertension, type 2 diabetes, and mild chronic kidney disease. His initial vitals are Temperature 38.8°C, heart rate 118 bpm, blood pressure 82/48 mmHg, respiratory rate 28 bpm, SpO₂ 90% on room air, and Glasgow Coma Scale (GCS) score of 14. He looks mottled, has delayed capillary refill, crackles at the right base, and dry mucous membranes. A chest x-ray suggests right lower-lobe pneumonia. Labs show white blood cell count (WBC) 17,000, creatinine 1.8 mg/dL, and lactate 3.4 mmol/L. Blood cultures are drawn, broad-spectrum antibiotics are started, and he receives 1 litre of balanced crystalloid. Thirty minutes later, his mean arterial pressure (MAP) remains around 60 mmHg. The resident asks: “Should we give more fluid to get to 30 mL/kg, or start norepinephrine now?” Background: Sepsis remains one of the highest-stakes and humbling diagnoses in emergency medicine. It is not as simple as infection plus abnormal vitals. Sepsis-3 reframed sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, moving away from the older SIRS-based definition and retiring the term severe sepsis. Septic shock is now generally understood as sepsis with persistent hypotension requiring vasopressors to maintain a MAP of at least 65 mmHg, with lactate greater than 2 mmol/L despite adequate volume resuscitation. For emergency physicians, the challenge is that sepsis is still largely a clinical diagnosis without a gold standard test. Systemic Inflammatory Response Syndrome (SIRS) is sensitive (true-positive) but not specific (true-negative). qSOFA may predict mortality, but it is not sensitive enough to rule out sepsis in the ED. Lactate is useful for risk stratification, but it's not a magic wand, and procalcitonin is not accurate enough to rule in or rule out bacterial infection. The SGEM has repeatedly emphasized that sepsis screening tools, biomarkers, and bundles should be used with healthy skepticism rather than blind obedience. Treatment in the ED usually starts with the basics: recognize the patient may be septic, obtain cultures when appropriate without delaying care, give early appropriate antimicrobials, seek source control, and support perfusion. The resuscitation controversy has evolved over two decades. Early goal-directed therapy (EGDT) gave way to usual-care trials that challenged protocolized central venous pressure and ScvO₂ targets. Fixed fluid mandates have been questioned, and many clinicians now worry about both under-resuscitation and fluid overload. As SGEM has argued, whether rigid bundles based on low-certainty evidence improve patient-oriented outcomes (POO). That leaves a very practical bedside question: after an initial litre or two, should we keep pouring in crystalloid, or should we start vasopressors earlier? Fluids can improve preload and perfusion, but excessive fluid administration may worsen pulmonary edema, tissue edema, and organ dysfunction. Vasopressors can restore vascular tone and perfusion pressure, but raise concerns about ischemia, monitoring, IV access, and intensive care unit (ICU) resource use. This is exactly the kind of EM question that deserves a patient-oriented answer. As we say on the SGEM, they are called guidelines, not GODlines. Clinical Question: In adult ED patients with early septic shock, does a strategy of restricted fluids and early vasopressors, compared with more liberal fluids and later vasopressors, increase days alive and out of hospital at 90 days? Reference: The ARISE FLUIDS Investigators. Vasopressors or Fluids in Early Septic Shock. NEJM June 2026. Population: Adults presenting to the ED with clinically suspected infection, systolic blood pressure (SBP) 2 mmol/L, and IV antimicrobials started. Exclusions: Key ones included >2000 mL IV fluids before enrollment, >6 hours since ED presentation, care limitations, immediate surgery, and clinician-determined unsuitability. Intervention: Restricted fluid strategy with early vasopressors. IV resuscitation fluids were stopped after randomization; vasopressors were started, with 250 mL boluses permitted for specified signs of persistent hypoperfusion. Comparison: Greater fluid volume with later vasopressors. Patients received up to 1000 mL initially, then 500 mL boluses for persistent hypotension or hypoperfusion; 30 mL/kg within 3 hours was recommended unless contraindicated. Outcome: Primary Outcome: Days alive and out of hospital from randomization to day 90. Secondary Outcomes: Mortality at 28 and 90 days, survival time to day 90, days alive and at home at day 90, days alive and free from organ support at day 28; tertiary and safety outcomes included discharge timing, in-hospital mortality, organ support, pulmonary edema, ischemia, and peripheral vasopressor complications. Type of Study: Investigator-initiated, multicenter, open-label, parallel-group randomized controlled trial. Authors’ Conclusions: “Among adult patients who presented to the emergency department with septic shock, an approach that involved restricted fluid volume and early vasopressors did not result in a greater number of days alive and out of the hospital at day 90 than an approach involving greater fluid volume and later administration of vasopressors.” Quality Checklist for Randomized Clinical Trials (Yes, No or Unsure): Did the study population include or focus on those in the emergency department? Yes Were the patients adequately randomized? Yes Was the randomization process concealed?. Yes Were the patients analyzed in the groups to which they were randomized? Yes Were the patients recruited consecutively, with no selection bias? No Were both groups similar with respect to prognostic factors? Yes Were all participants, clinicians, and outcome assessors blinded to group allocation? No Were all groups treated equally except for the intervention? Unsure Was follow-up complete, meaning at least 80% for both groups? Yes Were all patient-important outcomes considered? Yes Was the treatment effect large enough and precise enough to be clinically significant? No Who funded the trial? The trial was funded by the Australian National Health and Medical Research Future Fund and the New Zealand Health Research Council. The appendix states the funders had no role in design, conduct, analysis, interpretation, or reporting. Did the authors declare any conflicts of interest? At least two authors had potentially relevant professional/industry disclosures. However, there were no obvious trial-specific commercial conflicts apparent. Key Results: In adult ED patients with early septic shock, restricted fluids with early vasopressors did not improve days alive and out of hospital at 90 days compared with a more liberal fluid strategy and later vasopressors. Primary Outcome: Median days alive and out of hospital at day 90 were 76 days in both groups: 76 days (IQR 55–83) vs 76 days (IQR 55–82), difference 0.0 days, 95% CI −2.7 to 2.7, P=1.00. Secondary Outcomes: Mortality appeared similar: 28-day mortality 12.9% vs 10.0%, and 90-day mortality 16.4% vs 14.4%. Days alive and at home at day 90 were also similar. Invasive ventilation and renal replacement therapy were similar. Pulmonary edema was lower in the vasopressor group, 0.6% vs 5.0%, though the authors noted this could partly reflect reporting bias in an unblinded trial. 1. Modified Intention-To-Treat Analysis: The trial randomized 1000 patients, but 37 patients were excluded because informed consent or permission for data use was not obtained, leaving 963 patients in the analyzed population. This was balanced between groups and is unlikely to overturn the result, but it is not a pure intention-to-treat analysis (ITT). A strict ITT analysis preserves the prognostic balance created by randomization and avoids post-randomization exclusions. 2. Selection Bias & External Validity: This trial applies to a selected group of adult ED patients with early septic shock after at least 1 L but not more than 2 L of IV fluid, lactate >2 mmol/L, antibiotics started, and randomization within a narrow ED time window. Many real-world septic shock patients were excluded, including those who had received >2 L of fluid, presented late, required immediate surgery, had treatment limitations, had imminent death, had low likelihood of 90-day survival, or were judged by clinicians to be unsuitable for one or both treatment arms. This makes the trial highly relevant to early ED septic shock, but less applicable to patients who are already fluid overloaded, profoundly hypovolemic, perioperative, late-presenting, transferred, palliative, or outside systems where peripheral vasopressors and ICU-level monitoring are readily available. Open Label 3. Open-Label: Patients and treating clinicians were not masked to group assignment. This is understandable for a fluids-versus-vasopressors strategy trial, but it can influence clinician-mediated decisions such as additional fluid boluses, vasopressor initiation, corticosteroid use, ICU admission,...

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