The Skeptics Guide to Emergency Medicine

Date: March 11th, 2021 Guest Skeptic: Dr. Robert Edmonds is an emergency physician in the US Air Force in Ohio. DISCLAIMER: THE VIEWS AND OPINIONS OF THIS PODCAST DO NOT REPRESENT THE UNITED STATES GOVERNMENT OR THE US AIR FORCE. Reference: Post et al. Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial. Lancet 2021 Case: You’re working a busy evening shift in your community emergency department (ED) when a 58 year old female presents with a rapid onset terrible intensity headache.  She has no significant headache history and you are concerned for subarachnoid hemorrhage so you order a head CT which confirms your suspicions.  You page neurosurgery at the bigger ED in town, and while you wait for the page back, you wonder if giving tranexamic acid (TXA) could help improve the patient’s chances for a good outcome given its effects in other bleeding processes. Background: In the case presented, the woman would qualify using the Ottawa SAH Rule because of the rapid onset of an intense headache and her age. We have discussed the incredible work done by Dr. Jeff Perry and his group in the development of the Ottawa SAH Rule. Jeff was actually on the SGEM as the guest skeptic discussing this clinical decision instrument way back in 2013 (SGEM#48). The Ottawa SAH Rule is to be applied to alert patients older than 15 years of age with new severe non-traumatic headache reaching maximum intensity within one hour. It is not meant for patients with new neurologic deficits, previous aneurysms, SAH, brain tumor, or who have a history of recurrent headaches. This is defined as at least three or more episodes over the course of at least six months. Our SGEM Bottom Line eight years ago was that the Ottawa SAH “Tool” was not ready for prime time to rule out low risk patients from investigations. Fast forward to 2018 and the validation of the Ottawa SAH Rule by Dr. Perry and his group. The results of this prospective observational study were that the clinical decision instrument was 100% sensitive (missed no SAH patients) and 13.6% specific. Dr. Chris Carpenter The guest skeptic for SGEM#201 was Dr. Chris Carpenter, who literally wrote the book on diagnostic accuracy of clinical decision instruments in the ED with Dr. Jesse Pines. The SGEM bottom line from the episode was that the Ottawa SAH Rule needs external validation, a meaningful impact analysis performed, and patient acceptability of incorporating this rule into a shared decision-making instrument before being widely adopted. Dr. Perry did publish a prospective implementation of the Ottawa SAH Rule (Stroke 2019). This article was covered on the SGEM with EM Nerd Dr. Rory Spiegel. The results demonstrated that the Ottawa SAH Rule is highly sensitive (100%) but has very poor specificity (13%). It is unclear how it performs against unstructured clinical judgement or in non-urban tertiary care teaching hospitals (SGEM#283). Another issue the case brings up is whether a CT scan is good enough to rule out a SAH. The debate has historically been about whether or not you need to also get a lumbar puncture on these patients after a non-contrast CT head. Dr. Jeff Perry This brings us back to more work done by Jeff Perry. His team published a prospective cohort study that suggested if you got the CT scan done within six hours of headache onset, it was a third generation CT scanner, and it was read by a neuroradiologist, then you did not need to get an LP to rule out a SAH (BMJ 2011). There were some limitations to this observational study. Another study was done in the UK that tried to address this issue of LP post normal CT. This was covered on SGEM#134. It found that the NNTap (number needed to Tap) to diagnose one aneurysm not identified by CT scan was 250. The final issue the case identified was the use of TXA in treating patients with a SAH. We are skeptical given the previous review we did on the topic (SGEM#236). This was a structured critical review of the 2018 TICH trial published in the Lancet. The primary outcome showed no superiority of TXA compared to placebo for the mRS at 90 days. The SGEM bottom line was that TXA does not currently have evidence of improving outcomes in hemorrhagic stroke and routine administration cannot be recommended at this time. However, as good healthy skeptics our positions are tentative and will change when presented with convincing evidence. Just because TXA was not demonstrated to “work” in one RCT does not mean we can claim TXA does not work. The burden of proof is on those making the claim of efficacy. Patients deserve the best care, based on the best evidence. TXA has been discussed on the SGEM numerous times for treating a variety of conditions including: Trauma, isolated traumatic brain injury, gastrointestinal bleeding, post-partum hemorrhage and epistaxis.  Although some EM docs would like to believe TXA is one of the universal duct tapes of the ED, it has mixed results. Patients suffering an aneurysmal SAH are at risk of rebleeding, which could worsens their long term clinical outcome and chance of death.  A hypothesis raised in the previous Sprigg et al RCT was that perhaps by treating these people earlier with TXA they would have a patient-oriented benefit. Clinical Question: Does rapid administration of tranexamic acid in patients with CT confirmed SAH improve clinical outcome? Reference:  Post et al. Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial. Lancet 2021 Population: Adults 18 years and older with signs and symptoms for less than 24 hours indicating subarachnoid hemorrhage (SAH) AND who have a non-contrast CT confirming SAH. Exclusions: Perimesencephalic bleed in combination with a GSC score of 13–15, and without loss of consciousness directly after ictus or focal neurological deficit on admission; traumatic SAH; ongoing treatment for VTE (DVT/PE); a history of a hypercoagulability disorder; pregnancy; severe renal failure, or imminent death within 24 h. Intervention: TXA 1g IV bolus as soon as possible after a non-contrast CT proven diagnosis of SAH. This was followed by 1g infusion every 8 hours up to 24 hours (4g total) or until endovascular or surgical treatment, whichever came first. Comparison: Usual care Outcome: Primary Outcome: Neurologic outcome dichotomized to good (mRS of 0-3) or poor (mRS 4-6) at six months Secondary Outcomes: Excellent clinical outcome (mRS 0-2), ordinal shift of the mRS score, all-cause mortality (30 days and 6 months) and serious adverse events. Authors’ Conclusions: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale. Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Unsure 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. 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. No Results: The cohort consisted of 955 patients with a mean age of 58 years and two-thirds were female. The median time from ictus to CT scan was 93 minutes and the median time from signs and symptoms suggestive of SAH and TXA was 185 minutes.  Key Result: No superiority of TXA compared to usual care for patients with a subarachnoid hemorrhage. Primary Outcome: Good clinical outcome (mRS 0-3) 60% TXA vs 64% control Adjusted Odds Ratio (aOR) 0.86 ( 95% CI; 0.66 to 1.12) Secondary Outcomes:  Excellent clinical outcome (mRS 0-2): 48% TXA vs 56% control, aOR 73 (95% CI; 0.57 to 0.95) Ordinal shift of the mRS: No statistical difference All-cause mortality at 30 days (22%) and 6 months (26%): No statistical difference Adverse events: No statistical difference 1. Open label: The patient, investigators, and clinicians treating the patient were ALL aware of the patient’s inclusion in the treatment arm of the trial. This opens the study to significant biases. It’s unknown why the authors elected to pursue an open label study instead of providing the control group with a placebo, as this would have reduced the chances for bias significantly. 2. Patient Selection: It was not stated in the methods section that these were ED patients but it is likely that they were from the ED. They also did not explicitly say the patients were recruited consecutively 24/7/365. Twenty patients allocated to the TXA group did not receive treatment with nine of the twenty for “unknown” reasons. Patients were also excluded on the subjective assessment that death was imminent within 24 hours. These factors could have introduced some selection bias into the cohort of included patients. 3. Subgroup Analysis: The authors state that their findings show that routine use of TXA in spontaneous SAH cannot be recommended. However, the fact that their secondary outcome of excellent clinical outcome (mRS 0-2) was worse in the TXA group by a statistically significant amount is concerning. We need to be careful not to over-interpret subgroup analyses.

Date: March 4th, 2021 Guest Skeptic: Dr. Anand Swaminathan is an Assistant Professor of Emergency Medicine at St. Joseph’s Regional Medical Center in Paterson, NJ. Managing editor of EM:RAP and Associate Editor at REBEL EM. Reference:  Reuben A et al. The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial. Ann Emerg Med 2021 Case: A 70-year-old man presents with epistaxis. He’s got a history of atrial fibrillation and hypertension. His medications include apixaban, metoprolol and perindopril. He states that the nosebleed started that morning all of a sudden. Vitals are; a blood pressure 145/73 mmHg, heart rate 64 beats/minute, and oxygen saturation 99% on room air. You apply direct pressure for 10 minutes, but the bleeding continues. You administer phenylephrine topically, reapply pressure and, consider the use of tranexamic acid (TXA). Background: Epistaxis is a common Emergency Department (ED) complaint with over 450,000 visits per year and a lifetime incidence of 60% (Gifford 2008, Pallin 2005). The majority of refractory hemorrhages are seen in the elderly and in more than two-thirds of the time no cause for the epistaxis is identified. Standard anterior epistaxis treatment consists of holding pressure, use of local vasoconstrictors, topical application of silver nitrate and placement of an anterior nasal pack. The most common vasoconstrictor used in the US is oxymetazoline.  Emergency physicians have multiple tools in the toolbox to address this condition. We covered the topic of epistaxis on SGEM#53: Sunday Bloody Sunday. That episode we discussed 11 questions concerning epistaxis. It is a great review on the management of nosebleeds. The episode included the Dundee protocol for adult epistaxis management from 2012. I searched and could not find an updated version. ED patients with epistaxis often fail conservative management and end up with anterior nasal packs which are uncomfortable. This is even more common in the group of patients who are taking antiplatelet agents or anticoagulants. In recent years, TXA has been added to many physicians’ armamentarium based on a few relatively small studies. We reviewed two  of these randomized control trials (RCTs) on the SGEM including the 2018 publication looking at using TXA in patients taking antiplatelet drugs. (SGEM#210). Some of these RCTs looking at TXA for epistaxis have also been reviewed on REBEL EM and other FOAMed sites. The results were encouraging. Topical TXA has minimal safety concerns and is relatively inexpensive. However, the studies did have a number of limitations including, being single centered, relatively small sample sizes and a lack of blinding. The SGEM structured critical review was skeptical of TXA for treating nosebleeds and had a conservative bottom line: Despite some limitations in this un-blinded trial, topical tranexamic acid appears to improve some patient important outcomes in patients who are taking antiplatelet medications who present with epistaxis. Clinical Question: Does the use of topical, intranasal TXA reduce the need for application of anterior nasal packing in ED patients with epistaxis who fail conservative management? Reference:  Reuben A et al. The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial. Ann Emerg Med 2021 Population: Patients older than 18 years of age presenting with persistent epistaxis after local pressure and/or ice was applied to the bridge of the nose for at least 10 minutes. If bleeding persisted (continued presence of blood on the upper lip after wiping emanating from the nares) patients were treated with cotton wool dental roll soaked with a topical vasoconstrictor and inserted into the affected nostril for 10 minutes. If the bleeding persisted after the removal of the vasoconstrictor dental roll, they were enrolled in the trial. Exclusions: Hemodynamic unstable patients, epistaxis due to trauma, out-of-hospital packing, allergy to TXA, ENT thought should be excluded, nasopharyngeal malignancy, pregnancy, hemophilia, and inability or unwillingness to provide consent. Intervention: Tranexamic acid (TXA) 200 mg in 2 ml applied to a cotton wool dental roll (could packing be repeated once). Dental roll held in place for 10 minutes with pressure. The treatments were done by EM consultants, junior house officers, or emergency nurse practitioners. Control: Cotton wool dental roll soaked in sterile water. Dental roll held in place for 10 minutes with pressure Outcome: Primary Outcome: Use of anterior nasal packing (of any type) during the index ED visit regardless of any other additional treatments (intention to treat analysis) Secondary Outcomes: Hospital admission, need for blood transfusion, recurrent epistaxis, thrombotic events, hospital reattendance within 1 week. Authors’ Conclusions: “In patients presenting to an ED with atraumatic epistaxis that is uncontrolled with simple first aid measures, topical tranexamic acid applied in the bleeding nostril on a cotton wool dental roll is no more effective than placebo at controlling bleeding and reducing the need for anterior nasal packing.” Quality Checklist for Randomized Clinical Trials: 1. The study population included or focused on those in the emergency department. Yes 2. The patients were adequately randomized. Yes 3. The randomization process was concealed. Yes 4. The patients were analyzed in the groups to which they were randomized. Yes 5. The study patients were recruited consecutively (i.e. no selection bias). No 6. The patients in both groups were similar with respect to prognostic factors. Yes 7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes 8. All groups were treated equally except for the intervention. Yes 9. Follow-up was complete (i.e. at least 80% for both groups). Yes 10. All patient-important outcomes were considered. No 11. The treatment effect was large enough and precise enough to be clinically significant. No Results: The cohort consisted of 496 patients. The mean age was 71 years, slightly more male patients, 65% were taking anticoagulant medication, and 61% had hypertension. Key Result: No statistical difference in patients getting anterior packing between TXA and placebo Primary Outcome: Use of anterior packing Placebo 41.3% vs TXA 43.7% required packing (2.4% difference) Odds Ratio (OR) 1.107 (95% CI; 0.769 to 1.594; p=0.59) Secondary Outcomes:  No statistical difference in any of the secondary outcomes including recurrent epistaxis, hospital admission or blood transfusion Also, no statistical difference with a per-protocol analysis This is the largest trial and only double-blind study looking at topical TXA for epistaxis. The authors should be congratulated for successfully completing this multicentered study and getting it published. There are always limitations that need to be considered, even in very well-done studies. We will discuss five issues. 1. Patient Population: This is one of the major limitations to this study. It was a very select/narrow group of patients. There were 2,622 initially eligible but 2,126 (81%) were excluded. Almost 1/3 were excluded because a research nurse was unavailable. We understand that this is often a reality of doing research in an ED that is open 24/7/365. However, 29% of eligible patients were excluded for the reasons listed as “other”. What does that mean? Could it have introduced some subjectivity into excluding some patients but not others resulting in some selection bias? Also, when you drill down these are patients that have “failed” standard therapy of at least 10 minutes of pressure and/or ice on the bridge of their nose followed by another 10 minutes of anterior packing soaked in a vasoconstricting drug. In the US, the most common vasoconstrictor is oxymetazoline. It is unclear if one agent is superior to the other and thus, it’s unclear how this affects application of this evidence. The authors also excluded another 6% of patients if the emergency department was considered too busy. Was this objectively determined and if so how; wait times, length of stay, volume of patients, acuity of patients, or another metric? In addition, who made the decision that the department was too busy, EM consultant, junior house officer, nurse practitioner or the research assistant? Patients “expected” to be seen by the ENT in-patient team for specialist treatment were also excluded. They also did not include pregnant patients which is an example of women being under-represented in clinical trials. All these issues lead to a very narrow cohort of patients with epistaxis and some of these could have introduced an element of selection bias. 2. Anticoagulation: A super majority of patients included in the study (65%) were taking anticoagulant medication. There were no additional details given in the manuscript as to what type of anticoagulants the patients were using: DOACs (factor Xa inhibitors or direct thrombin inhibitors), vitamin K antagonists (warfarin), or low molecular weight heparin (enoxaparin). Also, we are unsure if the term anticoagulation includes antiplatelet drugs (ASA, clopidogrel, and ticagrelor)? The high proportion of select patients on anticoagulation with epistaxis who failed conservative treatment and packing with a topical vasoconstrictor could explain why no statistical difference was found between the intervention group (TXA) and the placebo group. 3. Dosing: The initial dose of TXA used was 200mg. The clinician could repeat the dose once if the bleeding persisted. This is different from the 500mg dose used in the previous TXA trials.

Date: February 18th, 2021 Guest Skeptic: Dr. Chris Bond is an emergency medicine physician and assistant Professor at the University of Calgary. He is also an avid FOAM supporter/producer through various online outlets including TheSGEM. Reference: Brichko et al. Rapid Administration of Methoxyflurane to Patients in the Emergency Department (RAMPED): A Randomised controlled trial of Methoxyflurane vs Standard care. AEM Feb 2021. Case: A 46-year-old female presents to the emergency department (ED) with sudden onset, severe right flank pain. She is pacing around at triage in tears and says she has a history of kidney stones. She is asking for something to help with her pain, but the department is very busy, and it will be some time before she can get into a treatment space. Background: Pain is the primary reason patients present to the emergency in many cases (1-6).  Oligoanalgesia is the term used to describe poor pain management through the under use of analgesia (7-11).  Effective pain management is an important indicator of the quality of patient care (12). Multiple factors have been thought to contribute to oligoanalgesia (overcrowding, language barriers, age, gender, ethnicity, insurance status) (13-16).  Delays in providing adequate analgesia leads to poorer patient outcomes, prolonged ED length of stay and reduced patient satisfaction (17, 18). It can take a long time for someone in severe pain to receive an analgesic in the ED. Previous research in Australia has shown that the median time can be between 40-70 minutes for analgesia administration (19, 20). Delays are not unique to Australia and a study done in the USA reported a mean of 116 minutes for patients presenting to the ED with pain to receive analgesia (21). To minimize delays, different strategies have been implemented to address the problem (advanced protocols, provision of oral analgesics at triage, and the use of novel analgesic agents that do not require intravenous access) (22). Recently, there has been increased interest in using methoxyflurane (Penthrox), an inhaled non-opioid analgesic, to provide rapid short-term analgesia (23, 24).  In Australia, Methoxyflurane has been widely used at sub-anesthetic doses for analgesia in the pre-hospital setting since 1975. Its use has become more global in recent years and at low doses, it has a very reassuring safety profile. Furthermore, there have been no reports of addiction or abuse related to these inhaler devices (25-28). The majority of studies of methoxyflurane for pain focus on traumatic pain, this study aimed to assess its effectiveness in treatment of both traumatic and non-traumatic pain. Clinical Question: What is the effectiveness of methoxyflurane versus standard care for the initial management of severe pain among adult ED patients? Reference:  Brichko et al. Rapid Administration of Methoxyflurane to Patients in the Emergency Department (RAMPED): A Randomised controlled trial of Methoxyflurane vs Standard care. AEM Feb 2021. Population: Adult patients aged 18-75 years with severe pain defined as an initial Numerical Rating Scale (NRS) pain score greater than or equal to 8. Exclusion criteria: Transferred patients, HR <40 or >140 bpm, SBP <90 or >180 mmHg, RR <6 or >36/min, GCS <15, possible ACS, headache, pregnancy, breastfeeding, known renal or hepatic failure, previous malignant hyperthermia, known sensitivity to fluorinated anesthetics, or agitated/aggressive per nursing staff. Intervention: Inhaled Methoxyflurane 3 mL Comparison: Standard analgesic care which could include paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), tramadol and oral oxycodone or IV morphine Outcome: Primary Outcome: Proportion of patients that had at least a 50% reduction in their pain score at 30 minutes Secondary Outcomes: Median pain score at 15, 30, 60 and 90 minutes, and the proportion of patients that achieved a >2 point drop in their pain score on the NRS. Additional secondary outcomes included data pertaining to adverse effects, both minor and major. Dr. Lisa Brichko This is an SGEMHOP episode which means we have the lead author on the show. Dr Lisa Brichko is an emergency physician working in a combination of private and public tertiary hospital Emergency Departments in Melbourne Australia. She has authored 24 peer-reviewed emergency medicine research publications primarily focusing on projects promoting safe and efficient patient care. This interest in improving the quality of care we can provide our emergency department patients has previously been developed through undertaking a Masters Degree in Health Management, attaining Associate Fellowship with the Royal Australasian College of Medical Administrators and her current role as Quality Improvement Manager on the emergency department leadership team for Cabrini Hospital. Authors’ Conclusions: “Initial management with inhaled methoxyflurane in the ED did not achieve the pre-specified substantial reduction in pain, but was associated with clinically significant lower pain scores compared to standard therapy.” 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. Unsure 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 Key Results: They randomized 121 patients into the RAMPED study and data was available for analysis in 120 patients. The mean patient age was 42 years and 51% were female. 84% of patients were enrolled during daytime hours (0700-1800). The vast majority of patients arrived by private transport with only 4% arriving by ambulance. There was no statistical difference in the primary outcome between methoxyflurane and standard care. Primary Outcome: Reduction of pain score by >50% at 30 minutes 6 (10%) of patients in the methoxyflurane arm and 3 (5%) in the standard care arm (p=0.49) Hazard ratio (HR) for the favourable outcome was 1.07 (95% CI: 0.75-1.53, p=0.70) Secondary Outcomes:  The administration of methoxyflurane was associated with a significant reduction in pain score at all time points. See the show notes for table. The median time to rescue analgesia was longer in the methoxyflurane arm at 66 minutes compared to 46 minutes in the standard therapy arm (p=0.024) There were no serious adverse effects that could be attributed to the intervention and median ED LOS was similar between the two groups. We have ten nerdy questions for Lisa to help us better understand her study. Listen to her respond to each question on the SGEM podcast. 1. Convenience Sample: This was a convenience sample when research assistants were available. Do you think this could have impacted the results and if so, in what way? 2. Arrival: The vast majority (96%) of included patients in the cohort arrived by private vehicle. Only 4% of patients were brought in by ambulance. This number seems low to us. What this surprising to your team? Do you think this low number limits the generalizability of your results? 3. This One Goes to Eleven: Different outcome measures in pain trials have been used (29). Why did you choose an 11-point numerical ratings scale (NRS) for pain rating over other options (eg. Visual analogue scale)? 4. Age: One of your exclusion criteria was age. Why did you decide to exclude patients younger than 18 years of age and also those >75 years of age? There is evidence that children and older adults are at more risk for oligoanalgesia. 5. Hemodynamics: Another exclusion for your study was hemodynamic instability. This was defined as a heart rate < 40 or > 140 beats/min or a systolic blood pressure < 90 or> 180 mm Hg, I did not think methoxyflurane had a clinically significant impact on HR and BP (30). 6. Outcome: You measured the NRS up to 90 minutes. Would measuring time points beyond 90 minutes be useful in order to see if patients did not have adequate analgesia after 90 minutes? 7. Blinding: You did not have an active or placebo control (sham) in an attempt to blind this trial. All clinicians and participants were aware of group allocation. This could have biased the study. We understand the ethical concerns about using a placebo control (inhaled 0.9% saline) for patients with painful conditions. Did you consider having inhaled nitrous oxide as an active comparator? 8. Cost: Cost can be an important factor when considering a treatment modality in the ED. We say that with IV acetaminophen it was priced too high for broad adaptation in the USA. Do you know what the cost of methoxyflurane is compared to standard care? 9. Malignant Hyperthermia: Methoxyflurane is a volatile anaesthetic agent. It has the potential to trigger malignant hyperthermia. There has apparently only been only one incident of MH after administration in Australia (31).  Regardless, methoxyflurane is still contraindicated in those individuals thought to at risk for malignant hyperthermia (32). How concerned should we be about using this medication, and do you need to stock dantrolene because of the risk? 10. Aerosolizing: We are still in a global pandemic. Is there any concern to using this inhaler during COVID19?

Date: February 19th, 2021 This is an SGEM Xtra episode. I had the honour of presenting at the Lehigh Valley Health Network Grand Rounds on February 4th, 2021. The title of the talk "Dogmalysis: Five Medical Myths in Emergency Medicine". The presentation is available to listen to on iTunes and GooglePlay and all the slides can be downloaded using this LINK.   Five Medical Myths in Emergency Medicine Myth #1: The use of non-selective NSAIDs will cause a nonunion in long bone fractures Myth #2: Topical anesthetics will cause blindness if used in simple corneal abrasions for less than 48 hours Myth #3: Mild paediatric gastroenteritis is best treated with expensive oral electrolyte solutions Myth #4: Tranexamic acid (TXA) has been proven to saves lives and results in good neurologic function in patients with isolated traumatic brain injuries (TBI) Myth #5: Epinephrine in adult out-of-hospital cardiac arrests (OHCA) results in better patient-oriented outcomes (POOs) Each of the five myths is presented with some background information and the PICO (population, intervention/exposure, comparison and outcome). Key results are provided with a number of the study limitations (dog leash) identified. There is an SGEM bottom line and a link to the original SGEM episode to provide more results and critical appraisal. There is also a link to the original article for people to read the primary literature for themselves. Myth #1: The use of non-selective NSAIDs will cause a nonunion in long bone fractures When bones break, they usually heal with either surgical or non-surgical management. Sometimes the healing process can take longer than usual (delayed union), does not heal (non-union) or in poor alignment (malunion). Non-union is defined as “a failure of the fracture-healing process” and occurs in up to 1 in 10 fractures. Several risk factors have been associated with increased risk of delayed or non-union: issues about the fracture (open/closed, displacement, location, etc) tobacco use, older age, severe anemia, alcohol intake, diabetes, low vitamin D levels, hypothyroidism, poor nutrition, infection, open fracture and certain medications (ex. steroids).  One class of medication that has been implicated in negatively impacting bone healing is NSAIDs. Non-selective NSAIDs and COX-2 inhibitors. There have been multiple studies investigating this issue with mixed results. The final cohort consisted of 339,864 patients identified in over 15 years. Less than 1% were diagnosed with a nonunion (2,996/339,864). The mean age was in the 50’s and around 60% were female. The most common fractures were radius, neck of the femur and humerus. Key Result: Patients who filled prescriptions for selective COX-2 inhibitors and opioids but not non-selective NSAIDs were associated with an increased risk of nonunion. SGEM Bottom Line: There is no high-quality evidence to support the claim that non-selective NSAIDS cause an increased risk of nonunion. SGEM#317: Dese bones gonna heal again, with or without a non-selective NSAID Reference: George et al. Risk of Nonunion with Nonselective NSAIDs, COX-2 Inhibitors, and Opioids. J Bone Joint Surg Am. 2020 Myth #2: Topical anesthetics will cause blindness if used in simple corneal abrasions for less than 48 hours Even small corneal abrasions can cause significant pain because the cornea is highly innervated. The first documented use of topical ophthalmologic anesthetics was in 1818. A cocaine derivative was employed to effectively block nerve conduction in the superficial cornea and conjunctiva (Rosenwasser). A number of proposed dangers have limited the use of topical anesthetic agents for the treatment of corneal abrasion associated pain. These dangers include delayed healing secondary to mitosis inhibition and decreased corneal sensation. The latter issue is of concern because of the potential for the abrasion to progress to an ulcer without the patient noticing. Additionally, these agents may have direct toxicity to corneal epithelium with prolonged use, leading to increased corneal thickness, opacification, stromal infiltration, and epithelial defects. The fear of these complications has led to the pervasive teaching that topical anesthetics should never be used for outpatient management of corneal abrasions. This is reflected in the condemnation of their use in major Emergency Medicine textbooks, including Rosen’s and Tintinalli’s. Some of the evidence used to support the claim of local anesthetics causing corneal harm comes from case reports, animal models or local anesthetic injected directly into the anterior chamber of the eye for cataract surgery. More information on the where the no topical anesthetic use on corneal abrasions come from can be found on a REBEL EM blog post. They enrolled 118 patients into the trial. The median age was in the mid 30’s and 60% were male. Baseline NRS for pain was 7 out of 10. Just over 10% had a metallic foreign body and more than ¼ had another foreign body. Key Result: Topical tetracaine was highly effective in reducing pain from simple corneal abrasions. SGEM Bottom Line: Topical tetracaine use for 24-48 hours provides effective pain control and seems to be safe when prescribed early after corneal abrasions and you are confident it is only a simple corneal abrasion.   SGEM#315: Comfortably Numb with Topical Tetracaine for Corneal Abrasions Reference: Shipman et al. Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Annals of EM 2020 Myth #3: Mild paediatric gastroenteritis is best treated with expensive oral electrolyte solutions Gastroenteritis is a common illness in children and these children are at risk of dehydration from inadequate intake, excessive losses or both together. If children are unable to tolerate oral hydration we often have to use intravenous fluids and sometimes require admission to hospital for ongoing fluids. Goldman et al Pediatrics in 2008 published a helpful table describing the degree of dehydration in children ranging from mild, moderate to severe. Most cases of gastroenteritis are mild, self-limiting and can be treated effectively with oral rehydration. For more information on visit this site on Oral Rehydration Therapy. The Canadian Pediatric Society also has an algorithm for oral rehydration. Children with vomiting from gastroenteritis, and mild-moderate dehydration, should have a trial of oral rehydration therapy. Failing this, ondansetron should be administered. Failing that, intravenous fluid should be considered. 3,668 children presenting to the emergency department were assessed for eligibility. There were 647 children randomized into the study (n=323 for half-strength apple juice/preferred fluids and n=324 for electrolyte solution). The majority of exclusions were because no research personnel were present to enroll the child (1,297). It was about evenly split between boys and girls and the mean age was 28 months. There were not differences between groups at baseline. Key Result: Treatment failure was seen in 16.7% half-strength apple juice and preferred fluid group vs. 25.0% electrolyte solution group. SGEM Bottom Line: When advising parents with children with mild gastroenteritis and minimal dehydration, offering half-strength apple juice and preferred fluids compared to electrolyte solutions is a better choice. SGEM#158: Tempted by the Fruit of Another – Dilute Apple Juice for Pediatric Dehydration Reference: Freedman et al. Effect of dilute apple juice and preferred fluids vs. electrolyte maintenance solution on treatment failure among children with mild gastroenteritis: A randomized clinical trial. JAMA. May 2016 Myth #4: Tranexamic acid (TXA) has been proven to saves lives and results in good neurologic function in patients with isolated traumatic brain injuries (TBI) TXA is a synthetic derivative of lysine that inhibits fibrinolysis and thus stabilizing clots that are formed. We have covered TXA as a treatment for bleeding a number of times on the SGEM. The evidence for TXA providing a patient-oriented outcome (POO) has been mixed. TXA seems to work for epistaxis, fails to cause a decrease in all-cause mortality in post-partum hemorrhage, does not demonstrate an improved neurologic outcome in hemorrhagic strokes but does have 1.5% absolute mortality reduction in adult trauma patients. Epistaxis – SGEM#53 and SGEM#210 Post-Partum Hemorrhage – SGEM#214 Stroke due to Intracranial Hemorrhage – SGEM#236 CRASH-2 Trial – SGEM#80 REBEL EM has also looked at TXA for those conditions plus a few others. It is unclear if it provides a benefit for gastrointestinal bleeds (GIB). Nebulized TXA shows promise for both post-tonsillectomy bleeding and hemoptysis. However, better studies are needed to confirm these observations. Zehtabchi et al published a SRMA of TXA for traumatic brain injuries (TBI). They found only two high-quality randomized control trials with 510 patients having TBI that met inclusion criteria. The results were no statistical difference in in-hospital mortality or unfavorable neurologic functional status. However, there was a statistical reduction in intracranial hematoma expansion size with TXA compared to placebo. The CRASH-3 investigators randomly allocated 12,737 patients with TBI to receive either TXA or placebo. There were 9,202 (72%) who were enrolled within 3 hours of injury. The mean age was 42 years, 80% were male, 80% had both pupils reactive and about 2/3 had a GCS less than 12. Key Result: No statistical difference in head-injury related mortality with TXA compared to placebo. SGEM Bottom Line: We cannot recommend the routine use of TXA for patients with isolated traumatic brain injuries at this time. SGEM#270: CRASH-3 TXA for Traumatic Head Bleeds?

Date: February 12th, 2021 Guest Skeptic: Dr. Dennis Ren is a paediatric emergency medicine fellow at Children’s National Hospital in Washington, DC. Reference: Mintegi S et al. Clinical Prediction Rule for Distinguishing Bacterial from Aseptic Meningitis. Pediatrics 2020 Case: A 4-year-old immunized girl presents to the emergency department (ED) with a fever and rhinorrhea for the past four days. Her parents report that she has been complaining of a headache and seems more tired and sleepy in the past day. On exam, she is febrile to 38.5 ºC, appears tired, with meningismus on examination but answers questions appropriately. She does not have any petechiae or purpura on skin exam. You explain that you must obtain some blood for laboratory work and perform a lumbar puncture (LP) because you are concerned that she has meningitis. Her nervous parents agree to the LP. Her cerebrospinal fluid appears clear and preliminary cerebrospinal fluid (CSF) results show a pleocytosis with 16 white blood cells per µL without any red blood cells. Her parents ask you whether or not she will have to stay in the hospital or receive antibiotics. Background: Vaccines cause adults. Supporting this position is that since the introduction of conjugate vaccines the incidence of life-threatening bacterial meningitis has decreased. The first conjugate vaccine introduced was the haemophilus influenzae type b (Hib) vaccine. This vaccine has a reported efficacy of 98% (Makwana and Riordan 2007). The success of conjugate vaccines is that most cases of pediatric meningitis are now aseptic (viral cause). It is important to distinguish between bacterial vs aseptic meningitis. This is because bacterial meningitis is associated with serious morbidity and mortality and requires prompt antibiotic treatment; aseptic meningitis is self-limited and requires only supportive care. Patients with suspected bacterial meningitis require hospital admission with empiric antibiotics pending culture results (Sáez-Llorens and McCracken 2003). There is no single variable that can help discriminate between bacterial vs. aseptic meningitis.  Combinations of variables have been tried in the past as part of clinical scoring systems such as the Bacterial Meningitis Score (BMS) to identify children with CSF pleocytosis at low risk for bacterial meningitis (Nigrovic et al 2002). However, BMS did not take into account C-reactive protein and procalcitonin levels that have shown promise in risk stratifying febrile children at risk for bacterial infection (Van den Bruel et al 2011). Additionally, BMS has missed a few cases of bacterial meningitis. Specifically, 2 out of 1714 patients categorized as very low risk for bacterial meningitis had bacterial meningitis (sensitivity 98.3%, NPV 99.9%). Both patients missed were younger than 2 months old (Nigrovic et al 2007). The study we are reviewing today aimed to develop and validate a more accurate scoring system called the Meningitis Score for Emergencies (MSE) to distinguish between bacterial vs. aseptic meningitis in children 29 days to 14 years old with CSF pleocytosis based on four objective lab criteria. Clinical Question:  Can a clinical decision tool using laboratory data help distinguish between bacterial from aseptic meningitis in children 29 days to 14 years old with cerebrospinal fluid pleocytosis? Pleocytosis- CSF WBC ≥10 cells per µL. Corrected for presence of CSF RBCS (1:500 leukocytes to erythrocytes in peripheral blood) and CSF protein (every 1000-cell increase on CSF RBCs per mm3, CSF protein increased by 1.1 mg/dL) Bacterial meningitis defined as patient with either identification of bacterial pathogen in CSF culture and/or Neisseria meningitides or Streptococcus pneumoniae on polymerase chain reaction and either positive blood culture or blood PCR result for N meningitides or S pneumoniae Aseptic meningitis defined as CSF pleocytosis and negative CSF and blood bacterial cultures and negative Neisseria meningitidesor Streptococcus pneumoniae on polymerase chain reaction Reference: Mintegi S et al. Clinical Prediction Rule for Distinguishing Bacterial from Aseptic Meningitis. Pediatrics 2020 Population: Children between 29 days and 14 years old with a diagnosis of meningitis across 25 Spanish emergency departments. Exclusion: Children <29 days old, critically ill, with purpura, not previously healthy or treated with antibiotics within 72 hours before lumbar puncture. Intervention: Retrospective derivation and prospective validation of Meningitis Score for Emergencies (MSE) for distinguishing bacterial vs. aseptic meningitis using procalcitonin >1.2 ng/mL, CSF protein >80 mg/L, CSF absolute neutrophil count >1000 cells per mm3, and C-reactive protein >40 mg/L. The four laboratory components were given different points if present and zero points if absent. So, if the procalcitonin was elevated you got 3 points, 1 point for elevated CRP, 1 point for elevated ANC and 2 points for elevated CSF protein (max score 7). Comparison: Bacterial meningitis score (Pediatrics 2002), validated (JAMA 2007) The BMS had 5 components: four are laboratory and one is clinical (seizure at or before presentation). Each of these components were also given a different number of points if present and zero points if absent. The BMS is available on MDCalc. Outcome: Accuracy of clinical decision support tool in distinguishing bacterial vs aseptic meningitis in children with CSF pleocytosis. (sensitivity, specificity, negative predictive value, positive predictive value, and likelihood ratios). Authors’ Conclusions: “The meningitis score for emergencies (MSE) accurately distinguishes bacterial from aseptic meningitis in children with CSF pleocytosis.” Quality Checklist for Clinical Decision Tools: The study population included or focused on those in the ED. Yes The patients were representative of those with the problem. Unsure All important predictor variables and outcomes were explicitly specified. Yes This is a prospective, multicenter study including a broad spectrum of patients and clinicians (level II). No Clinicians interpret individual predictor variables and score the clinical decision rule reliably and accurately. Yes This is an impact analysis of a previously validated CDR (level I). No For Level I studies, impact on clinician behavior and patient-centric outcomes is reported.  N/A The follow-up was sufficiently long and complete. Unsure The effect was large enough and precise enough to be clinically significant. Unsure Key Results: The final study included 1,009 patients between 29 days and 14 years of age. There were 819 patients assigned to the derivation group while 190 were assigned to the validation group. Slightly over 1/3 were female with mean age of 2 years. The vast majority (91%) had aseptic meningitis and only 9% had bacterial meningitis. Of those with meningitis, 80% had either N meningitides (41.3%) or S pneumonia (38.5%). Other organisms included: Group B Strep 5.5%, Strep pyogenes 4.3%, Enterococcus faecalis, H influenzae (2.2% each) and E. coli, Listeria monocytogenese, Salmonella typhimurium, Strep bovis, Kingella kingae, Fusobacterium necrophorum (1.1% each). Validation Group MSE ≥1: Sensitivity 100%, specificity  77.4%, NPV 100%, PPV 46.3%, LR+ 4.4 and LR- 0 Derivation and Validation Group MSE ≥1: Sensitivity 100%, specificity 83.2%, NPV 100%, PPV 37.4%, LR+ 5.95 and LR- 0. No patients with bacterial meningitis were missed with the MSE. Two patients with bacterial meningitis were missed with the BMS. 1-month-old with Streptococcus agalactiae meningitis although BMS is used for patients >2 months 3-year-old with meningococcal meningitis 1) Procalcitonin Testing: Procalcitonin is the cool new kid on the block when it comes to detecting bacterial infections. Procalcitonin testing may not be available at all hospitals limiting applicability of this new scoring tool. 2) Age: Similar to the Bacterial Meningitis Score (BMS) study, this study did not include any patients <29 days old. Unlike the BMS study that included patients up to age 19, this study does not include any patients over the age of 14. It is difficult to determine whether the incidence of aseptic vs bacterial meningitis in the age group >14 to 19 years would have affected the accuracy of the MSE. 3) Derivation vs Validation Sets: Out of a total of 1,509 eligible patients, 500 were excluded: 414 from derivation group, 86 from validation group. Proportionately, 50 patients (12%) with bacterial meningitis were excluded from the derivation group while 28 patients (32%) with bacterial meningitis were excluded from the validation set. This may suggest that the groups were uneven in their relative distribution of bacterial vs aseptic meningitis. When comparing the characteristics between patients in the final derivation and validation groups, there was also a higher percentage of bacterial meningitis in the validation set compared to the derivation set (16.3% vs 7.4%). 4) CSF Gram-Stain: The authors made a decision to not include CSF Gram-stain in the score despite it being positive in 75% of cases of bacterial meningitis and positive CSF Gram-stain having specificity >97%. They state that this is due to limitations of availability of performing Gram-stain 24/7 in all EDs but recommend that a child with CSF pleocytosis and positive Gram stain should be put on antibiotics regardless of MSE score. 5) Geography: One of the limitations mentioned by the authors is that this study population is drawn purely from Spanish emergency departments. The prevalence of bacterial meningitis differs worldwide so this scoring tool would need external validation in different counties and in rural vs urban areas.

Date: January 20th, 2021 Guest Skeptics: Dr. Thorben Doll and Dr. Johannes Pott. They are both fourth year resident doctors in anesthesiology, intensive care and emergency care in St. Bernward Hospital in Hildesheim, Germany. Thorben and Johannes have a knowledge translation project called Pin-Up-Docs. It is a German emergency medicine and intensive care podcast. Their mission is to share  knowledge with paramedics, nurses, medical student and also young doctors as they take their first steps in the field of emergency medicine.  Each month they post new content and focus two main topics, the medical therapy of the month as well as tricks for dealing with complex emergencies. All of their shared information is based on the latest medical studies and data. Additionally, they host selected guests for special episodes, and publish blogs dedicated to more advanced medical questions or topics. Reference: Ruberto et al. Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial. Annals of EM 2020. Case: A 32-year-old male patient presents to your emergency department (ED) with severe nausea, vomiting and abdominal pain. He reports the symptoms have been continuous for 4 or 5 hours. Over-the-counter medications like acetaminophen (paracetamol) and ibuprofen have not helped. His flatmate (roommate) says he only gets relief by taking really long, hot showers. On examination, his vital signs are normal, and he is afebrile. The abdomen exam shows no peritoneal sign and normal bowel sounds are heard. Laboratory values are unremarkable. An ultrasound does not show any free fluids or any signs of an Ileus, appendicitis or gallbladder disease. His pain and nausea are difficult to control with standard medications. You admit him to hospital and the next day he undergoes gastroscopy which is unremarkable. In the afternoon the patient is seen by a nurse when he is smoking “weed” (cannabis) in the garden of the hospital. He admits to being a heavy cannabis user and his symptoms do seem to get worse when smoking weed. You suspect he has cannabis hyperemesis syndrome and discharge him home with the recommendation to stop smoking as much weed. Background: Chronic marijuana use was recognized by Allen el al in 2004 to cause cyclical vomiting in patients from South Australia. Roche and Foster quickly reported in 2005 that this was not an isolated problem to the Adelaide Hills of South Australia. The medical condition became known as cannabinoid hyperemesis syndrome. We covered this on SGEM#46: Don’t Pass the Dutchie   Cannabis stimulates two receptors: CB1 and CB2. CB1 is also expressed in the GI-system and reduces motility and relaxes the esophageal sphincter tonus. If you conduct chronical cannabis abuse, it seems that the anti-nausea effect of cannabis vanishes and there is a continuous hyperstimulation of CB1. That’s why you have abdominal pain and nausea with continuous vomiting. There are some criteria proposed for the diagnosis of cannabinoid hyperemesis. An essential feature is long term cannabis use (often daily). There are five major features for the diagnosis and five supportive features for the diagnosis. These are listed in the table.  Clinical Question: Can haloperidol effectively treat patients with cannabis hyperemesis syndrome? Reference: Ruberto et al. Intravenous Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized, Controlled Trial. Annals of EM 2020. Population: Adult patients 18 years of age and older presenting to the ED with a working diagnosis of hyperemesis cause by cannabis who had at least two hours of ongoing, witnessed emesis or retching. Patients needed to report at least three episodes of emesis in a cyclic pattern separated by greater than one month during the preceding two years, and near-daily to daily use of cannabis by inhalation for at least six months. Exclusion: Daily opioid users, allergic to or intolerant of either study drug, deemed unreliable for follow-up, or unlikely to return for crossover, pregnant or received an antiemetic, anticholinergic or antipsychotic agent intravenously (other than up to 100mg of dimenhydrinate) in the previous 24 hours. Intervention: Haloperidol low-dose (0.05mg/kg) or high-dose (0.1 mg/kg) Comparison: Ondansetron 8mg IV Outcome: Primary Outcomes: Average reduction from baseline in abdominal pain and nausea scores measured on a 10-cm visual analog scale (VAS) at two hours after treatment Secondary Outcomes: Changes in either abdominal pain or nausea score over time, treatment success (ie, both abdominal pain and nausea <2 cm at !2 hours), being discharge ready at two hours, use of rescue antiemetics before discharge, time to discharge readiness, length of stay (LOS) greater than 12 hours, and unscheduled return visits within seven days. Any adverse events potentially related to the study drug and specifically any acute dystonia or moderate to severe akathisia. Authors’ Conclusions: “In this clinical trial, haloperidol was superior to ondansetron for the acute treatment of cannabis-associated hyperemesis. The efficacy of haloperidol over ondansetron provides insight into the pathophysiology of this now common diagnosis in many EDs”. 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. Unsure 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. 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 Key Results: There were 313 unique individuals with nausea, vomiting and cannabis use mentioned. A total of 65 patients met inclusion criteria when the research team was notified and only 30 (46%) agreed to participate and were randomized. The mean age was 29 years with slightly more men than women. Haloperidol was superior compared to ondansetron for pain and nausea at two hours post treatment. Primary Outcome: Haloperidol vs ondansetron change from baseline Nausea: –5.0 vs –2.4, difference –2.5 (95% CI; –4.4 to –0.6) Pain: –4.3 vs –2.1, difference –2.2 (95% CI; –4.4 to 0) Secondary Outcomes:  Haloperidol was superior to ondansetron in all secondary outcomes. Three patients had prespecified adverse events (one moderate akathisia and two return visits for acute dystonia) all after the higher dose haloperidol (0.1 mg/kg). All three patients were treated without difficulty, discharged, and withdrawn from further study eligibility for crossover, given the compromised blind. There were four return visits (two for dystonia and two for ongoing nausea and vomiting) within the week after haloperidol compared with six return visits (all for ongoing nausea and vomiting) after ondansetron. This was a difficult study to successfully complete due to the inclusion and exclusion criteria, the cross-over design and the target population. The researchers should be congratulated for the data they were able to obtain. 1) Convenience Sample: These were not consecutive patients but rather a convenience sample. Participants were recruited only when on-site research personnel were available to facilitate enrollment. Out of the 313 unique patients presenting with nausea/vomiting and cannabis use, 201 people were excluded because the research team was not notified, or it was after hours. This could have introduced some selection bias. 2) Selection Bias: Speaking of selection bias, another possible source of this type of bias was that less than 50% of eligible patients agreed to participate (30/65). The authors said this was often due to patients being skeptical regarding the diagnosis as disclosed during the consent process. Also, if the patient was deemed unreliable for follow-up, or unlikely to return for crossover they were excluded. This is a subjective criterion that could have introduced selection bias into the process. The researchers did were not very successful considering only 9 of 30 patients (30%) returned the 24- and 48-hour VAS scores despite reminders by telephone, text, and e-mail. 3) Small Population: This was a relatively small study with only 30 patients. They discussed the difficulties they had in reaching their prespecified enrollment target. Part of the problem was the inclusion criteria of needing witnessed emesis, the exclusion due to IV ondansetron being given as a standing medical order for all-cause emesis before clinical assessment, lack of research personnel (Nerdy point#1) and a belief by some clinicians that their practice approach was superior to the study protocol. Despite the small numbers, they did see a large effect size that was statistically and clinically significant. Another small number we should consider was the low crossover rate of 25% (being treated more than once). This means they could only perform an ANOVA for the first period alone for the primary efficacy analysis. 4) Stopped Early: This trial was stopped early. We have talked about this issue before on the SGEM. Guyatt et al discussed the problem in a 2012 BMJ article. They said: “Guidance must include a high level of skepticism regarding the findings of trials stopped early for benefit, particularly when those trials are relatively small and replication is limited or absent.”  However,

Date: January 22nd, 2021 Guest Skeptic: Dr. Steve Joseph. Steve completed his Sport Medicine fellowship training with the Fowler Kennedy Sport Medicine Clinic in 2017.  He served with the Canadian Forces as a Medical Officer and Flight Surgeon. Steve is currently an Assistant Professor in the Department of Family Medicine at Western University (London, Ontario) working at the Fowler Clinic and the Roth McFarlane Hand and Upper Limb Centre. Reference: George et al. Risk of Nonunion with Nonselective NSAIDs, COX-2 Inhibitors, and Opioids. J Bone Joint Surg Am. 2020 Case: A healthy 55-year-old woman was out for a walk and had a FOOSH (fall on outstretched hand) of her dominant arm. The X-ray demonstrates a fracture of the distal radius that is in an acceptable position and does not require a reduction. You immobilize her in a below elbow splint which provides significant pain relief and refer her to the local orthopedic fracture clinic. Upon discharge she asks what she should take for pain because she read somewhere that anti-inflammatory drugs like ibuprofen can prevent bone healing. She currently takes thyroid replacement therapy and has no known drug allergies. Background: There are conflicting studies about fracture healing and the use of non-steroidal anti-inflammatories (NSAIDs) in humans. It remains a controversial topic in the orthopaedic specialty. When bones break, they usually heal with either surgical or non-surgical management. Sometimes the healing process can take longer than usual (delayed union), does not heal (non-union) or in poor alignment (malunion). Non-union is defined as "a failure of the fracture-healing process” and occurs in up to 1 in 10 fractures. Several risk factors have been associated with increased risk of delayed or non-union. These factors include: Use of tobacco products, older age, severe anemia, alcohol intake, diabetes, low vitamin D levels, hypothyroidism, poor nutrition, infection, open fracture and certain medications (ex. steroids). The top risk factors for non-union according to a study by Santolini et al were open method of fracture reduction, open fracture, presence of post-surgical fracture gap, smoking, infection, wedge or comminuted types of fracture, high degree of initial fracture displacement, lack of adequate mechanical stability provided by the implant used, fracture location in the poor zone of vascularity of the affected bone, and a fractured tibia [1]. One class of medication that has been implicated in negatively impacting bone healing is NSAIDs. Non-selective NSAIDs block cyclooxygenase (COX)-1 and 2 while selective NSAIDs only inhibit COX-2. There have been multiple studies investigating this issue with mixed results. Clinical Question: Is there increased risk for fracture non-union with certain classes of NSAIDs? Reference: George et al. Risk of Nonunion with Nonselective NSAIDs, COX-2 Inhibitors, and Opioids. J Bone Joint Surg Am. 2020 Population: Adults (18 years and older) inpatient or outpatients with a diagnosis of certain long bone fractures (neck of femur/tibia/fibula/tibia and fibula/radius/ulna/humerus/clavicle) based on ICD-9 codes. Excluded: Patients less than 18 years of age, multiple fractures, metastatic disease, history of malunion fracture in the year prior or within 90 days Exposure: Filled prescription for a non-selective NSAIDs, selective COX-2 inhibitor and/or opioid within 30 days of the fracture Comparison: Not filling a prescription for a non-selective NSAIDs, selective COX-2 inhibitor and/or opioid within 30 days of the fracture Outcomes: Primary Outcome: Diagnosis of non-union within the 91 to 365 days post fracture. This was based on two definitions. The primary definition used ICD-9 code for nonunion with a procedure to treat nonunion within 30 days of the nonunion diagnosis. The secondary definition was an inpatient or outpatient diagnosis of nonunion. Authors’ Conclusion: “COX-2 inhibitors, but not non-selective NSAIDs, were associated with a greater risk of non-union after fracture. Opioids were also associated with non-union risk, although patients filling prescriptions for opioids may have had more severe fractures.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Unsure Was the exposure accurately measured to minimize bias? No Was the outcome accurately measured to minimize bias? Unsure Have the authors identified all-important confounding factors? Unsure Was the follow up of subjects complete enough? Yes How precise are the results? Fairly precise Do you believe the results? Yes Can the results be applied to the local population? Yes Do the results of this study fit with other available evidence? Yes Key Results: The final cohort consisted of 339,864 patients identified in over 15 years. Less than 1% were diagnosed with a nonunion (2,996/339,864). The mean age was in the 50’s and around 60% were female. The most common fractures were radius, neck of the femur and humerus. Patients who filled prescriptions for selective COX-2 inhibitors and opioids but not non-selective NSAIDs were associated with an increased risk of nonunion. Primary Outcome: Nonunion COX-2- inhibitor prescriptions: Adjusted odds ratio (aOR) 1.84 (95% CI; 1.38 to 2.46) Opioid prescriptions: aOR 1.69 (95% CI; 1.53 to 1.86), Non-selective NSAID prescriptions: aOR 1.07 (95% CI; 0.93 to 1.23) 1) Question: They answered the question about an association between filling a prescription for various analgesics and the risk of nonunion. However, the question we want answered is whether or not any of these medications has a causal relationship with nonunion. Stronger evidence would be an RCT of these medications with the outcome of nonunion confirmed clinically and not using ICD-9 codes. It would be difficult to get ethics approval for a placebo-controlled trial. It could also be a challenge to maintain blinding due to the side effect profile of opioids. 2) Cohort Recruitment: We were unsure if the cohort was recruited in an acceptable way to minimize bias. They used ICD-9 codes to identify the individuals with a fracture. There was no reference to support that this is a validated method. 3) Exposure: The exposure was only if the patient filled a prescription, not if they took the prescription. Some prescriptions may have been filled and missed. They did not describe the process well. Filling a prescription does not confirm if they took the medication or even how much and for how long. Non-selective NSAIDS are widely available over the counter medications which also could confound the results. We will talk more about confounders in nerdy point #5. 4) Outcome: Their outcome was based on two non-union definitions. Both relied on ICD-9 codes. They did not provide a reference validating the first definition. The second definition did have a reference. It was a small, single centre study with a positive predictive value of only 89% [2]. The authors of the cited study for the definition acknowledge these weaknesses in their discussion of limitations. This included the issue of PPV being based on prevalence of disease. 5) Confounders: They identified many confounders in their analysis like diabetes, alcohol, steroid use, and others. However, there are other confounders (severe anemia, low vitamin D levels, hypothyroidism, poor nutrition, etc) which have associated with nonunion that were not identified. This could have impacted the magnitude of the point estimate and the 95% confidence interval (precision of the results). Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors’ conclusions but would have added a qualification that other unmeasured confounders could have impacted the results. SGEM Bottom Line: There is no high-quality evidence to support the claim that non-selective NSAIDS cause an increased risk of nonunion. Case Resolution: You suggest using acetaminophen or ibuprofen for pain. Dr. Steven Joseph Clinical Application: This will not change my practice. I will prescribe according to the patient’s preferences, my clinical judgment and available evidence. This will mean usually suggesting non-selective NSAIDs or acetaminophen. Sometimes I will prescribe a short course of opioids. I do not use COX-2 inhibitors because there is no high-quality evidence of better efficacy or safety profile and this study suggests an increased associated risk of nonunion. What Do I Tell My Patient? Broken bones can be very painful. Immobilization often provides a great deal of pain relief. You can also use acetaminophen or ibuprofen to help with the pain. The goal is not to get to zero pain but to minimize suffering. There is no high-quality evidence that anti-inflammatory drugs like ibuprofen will prevent bone healing.  If the pain is getting worse, you are getting numbness, loosing function, the hand is going cold/pale or you are otherwise worried, please come back to the emergency department for reassessment. Keener Kontest: Last weeks’ winner was Garrision Lin. He is a nursing student at Western University and is currently doing a placement at South Huron Hospital Association. He knew the first Nurse Practitioner program in the US was in 1965 by Loretta Ford and Dr. Henry K. Silver from the University of Colorado. Listen to the SGEM podcast to hear this weeks’ question. Send your answer to TheSGEM@gmail.com with “keener” in the subject line. The first correct answer will receive a cool skeptical prize.   Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine. References: Santolini E, West R,

Date: January 20th, 2021 Guest Skeptic: Dr. Lauren Westafer an Assistant Professor in the Department of Emergency Medicine at the University of Massachusetts Medical School – Baystate. She is the cofounder of FOAMcast and a pulmonary embolism and implementation science researcher. Dr. Westafer serves as the Social Media Editor and  research methodology editor for Annals of Emergency Medicine and as an Associate Editor for the NEJM Journal Watch Emergency Medicine. Reference: Pines et al. Emergency Physician and Advanced Practice Provider Diagnostic Testing and Admission Decisions in Chest Pain and Abdominal Pain. AEM January 2021 Case: A 50-year-old male presents to the Emergency Department (ED) with left lower quadrant abdominal pain. The patient is seen by an advanced practice provider (APP). He wants to know if being seen by an APP alters his chance of diagnostic testing or hospital admission. Background: We covered the use of advanced practice providers (APPs) on the SGEM#308. That SGEMHOP episode asked how the productivity of APPs compare to emergency physicians and what is its impact on ED operations? The key result from that study of 13 million ED visits across 94 states was that physicians were more productive than PAs and NPs. The SGEM bottom line was that increasing APP coverage has minimal effect on ED flow and safety outcomes based on the data. Over the past two decades, the use of APPs has increased. APPs have a significantly truncated medical training (about 2 years of training) and practice experience compared with the traditional 4 years of medical school and 3-4 years of residency for emergency physicians. There has been a concern about post-graduate training of NPs and PAs in the ED. A joint statement on the issue was published in 2020 by AAEM/RSA, ACEP, ACOEP/RSO, CORD, EMRA, and SAEM/RAMS. The American Academy of Emergency Medicine (AAEM) has a position statement on what they refer to as non-physician practitioners that was recently updated. The American College of Emergency Physicians (ACEP) also has a number of documents discussing APPs in the ED. The difference in training between and emergency medicine physician and APPs is well recognized. A concern is that some APPs may compensate for this training gap by increased testing. Clinical Question: Is ED evaluation by an APP associated with higher test utilization and hospitalization compared with evaluation by a physician? Reference: Pines et al. Emergency Physician and Advanced Practice Provider Diagnostic Testing and Admission Decisions in Chest Pain and Abdominal Pain. AEM January 2021 Population: All ED patients with a chief complaint of chest pain or abdominal pain triaged as an Emergency Severity Index (ESI) 2,3, or 4 who were seen independently by either an APP or emergency physician Excluded: Patients who left without treatment or against medical advice, those who were dead on arrival or died in the ED. They also excluded those with a triage level ESI 1 or 5, as these are less common, as well as those with a final diagnosis of injury or poisoning – as in those cases the diagnosis would generally be apparent. Intervention: Evaluated by an APP Comparison: Evaluated a physicial Outcome: Primary Outcomes: Laboratory tests, ECGs, imaging studies as well as hospital admissions (including transfer to other hospitals and observation admissions) Secondary Outcomes: Testing based on evidence-based practice Dr. Jesse Pines This is an SGEMHOP episode which means we have the lead author on the show. Jesse Pines MD is the National Director for Clinical Innovation at US Acute Care Solutions and a Professor of Emergency Medicine at Drexel University. In this role, he focuses on developing and implementing new care models including telemedicine, alternative payment models, and also leads the USACS opioid programs. Authors’ Conclusions: “We demonstrate that the care delivered in the ED by advanced practice providers and emergency physicians for patients matched on complexity and acuity presenting with chest pain or abdominal pain chief complaints is largely similar with respect to diagnostic test utilization and admission decisions. Future research should continue to explore the optimal use of advanced practice providers in the ED and the best ways to deploy this expanding part of the U.S. ED workforce". Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Unsure Was the exposure accurately measured to minimize bias? Unsure Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? No Was the follow up of subjects complete enough? Yes How precise are the results? Fairly precise Do you believe the results? Yes Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Unsure Key Results: The data was collected over three years (2016-19) from around 90 facilities with over a thousand APPs and more than 1,500 emergency physicians. There were 663,599 patient visits for chest pain (12.8% seen by APPs and 87.2% seen by physicians). There were 946,042 patient visits for abdominal pain (21.3% seen by APPs and 78.7% seen by physicians). There was not much difference between APPs and physicians for laboratory, imaging studies or admissions with APPs being slightly lower for all outcomes. Physicians tended to see older patients, those with more comorbidities, and had a higher admission rate. In contrast, APPs tended to see younger patients, with less comorbidities and lower admission rates. However, once IPW-adjusted average treatment effects showed that being seen by an APP either reduced the probability or did not have a statistically significant impact the probability of having a laboratory test or imaging test ordered in comparison to physicians. This was consistent overall and among discharged ED visits, including models that contained past medical history. 1) Observational Study: One of the main limitations is this is an observational study. Although they stratified by age and did inverse propensity score weighting (IPW) there could have been confounding factors impacting the results. 2) Accuracy of Exposure Measurement:  Big datasets allow us to look at massive amounts of information. One problem, however, can be the granularity of the data. It’s not entirely clear in the manuscript how the exposure, which was whether an APP saw the patient or not, was determined. Was it that an APP was involved in any aspect of care? Was it that they saw the patient first? Last before disposition? In some EDs, while APPs may see patients primarily, physicians also see, evaluate, and help disposition the patient. In other EDs (or even the same ED but with different APP-attending physician combinations), the APP may truly independently see and manage the patient. These combinations make the exposure a little more opaque in this case. 3) Protocolized: Most of the patients (>90%) presenting with chest pain were adults. Often, they are being worked up for rule out ACS or rule out PE.  These tend to be very protocolized workups. There is also a zero-miss culture when it comes to MIs and PEs. It is not surprising that you did not find much variability in practice for patients presenting with chest pain. 4) Supervision: It says in the publication that all APPs had some degree of physician supervision and none were practicing independently. This is another reason why we would not expect to find much difference between APPs and physicians. 5) Patient-Oriented Outcome:  It could be argued that number of tests are not patient oriented outcomes depending on insurance status. A stronger case could be made about admission to hospital. Why not look at things like safety defined as mortality and morbidity? Martha Roberts We were correctly called out after SGEM#308 for not having an APP on the SGEM episode that reviewed a paper on APPs. Demonstrating that we listen to feedback and take action, Martha Roberts was invited to provide her comments on the paper. She is a critical and emergency care, triple-certified nurse practitioner currently living and working in Sacramento, California. She is the host of EM Bootcamp in Las Vegas, as well as a usual speaker and faculty member for The Center for Continuing Medical Education (CCME). She writes a blog called The Proceduralist and has started her own podcast with PA Mike Sharma called The 2-View podcast. Comment on Authors’ Conclusion Compared to SGEM Conclusion: We generally agree with the authors conclusions. SGEM Bottom Line: In patients presenting to the ED with chest pain and abdominal pain, physicians and APPs had similar practice patterns with test ordering and admissions rates. Case Resolution: The patient has a work-up for his abdominal pain, including labs and CT abdomen-pelvis, and is diagnosed with uncomplicated diverticulitis. He is discharged home with a prescription for appropriate antibiotics. Dr. Lauren Westafer Clinical Application: Unsure. We do not have high-quality data to inform us about the impact of APPs on the emergency department. This data comes from one large emergency department group and may lack external validity to other practice environments. What Do I Tell My Patient? It probably will not matter whether you see the APP or the physician. Both have similar practice styles, and the APP will be supervised by an attending physician. Keener Kontest: Last weeks’ winner was Kalmen Barkin an EMT from Somersworth, New Hampshire. They knew the term "blinding" came from an investigation into the practice of Dr. Franz Mesmer.

Date: January 5th, 2021 Reference: Shipman et al. Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Annals of EM 2020 Dr. Glaucomflecken Guest Skeptic: Dr. Will Flanary is an ophthalmologist, writer, and comedian who moonlights in his free time as “Dr. Glaucomflecken” on Twitter and TikTok. Effortlessly blending humor with education, Dr. Glaucomflecken has spent the last five years informing audiences on a wide range of topics, like navigating the confusing world of over-the-counter eyedrops, the horrifying consequences of sleeping in contact lenses, and his recent experiences as a patient in the medical system. Case: A 32-year-old healthy man presents with left eye pain. He was giving his 9-month-old a hug and got poked in the eye with a sharp little fingernail.  His visual acuity is 20/20 bilaterally and he doesn’t wear corrective lenses or contact lenses. He tried some over-the-counter red eye drops that did not seem to work. In the emergency department (ED), tetracaine drops are applied prior to slit lamp examination and the pain is completely resolved. On examination, you see a vertical corneal abrasion with no evidence of ulceration and no foreign body. You prescribe antibiotic drop and prepare to discharge him home when he asks, “can I get some of those numbing drops to use at home”? Background: Even small corneal abrasions can cause significant pain because the cornea is highly innervated. The first documented use of topical ophthalmologic anesthetics was in 1818. A cocaine derivative was employed to effectively block nerve conduction in the superficial cornea and conjunctiva (Rosenwasser). A number of proposed dangers have limited the use of topical anesthetic agents for the treatment of corneal abrasion associated pain. These dangers include delayed healing secondary to mitosis inhibition and decreased corneal sensation. The latter issue is of concern because of the potential for the abrasion to progress to an ulcer without the patient noticing. Additionally, these agents may have direct toxicity to corneal epithelium with prolonged use, leading to increased corneal thickness, opacification, stromal infiltration, and epithelial defects. The fear of these complications has led to the pervasive teaching that topical anesthetics should never be used for outpatient management of corneal abrasions. This is reflected in the condemnation of their use in major Emergency Medicine textbooks, including Rosen’s and Tintinalli’s. Some of the evidence used to support the claim of local anesthetics causing corneal harm comes from case reports, animal models or local anesthetic injected directly into the anterior chamber of the eye for cataract surgery. More information on the where the no topical anesthetic use on corneal abrasions come from can be found on a REBEL EM blog post. We covered and randomized control trial by Waldman et al on topical tetracaine for simple corneal abrasions on SGEM#83. The bottom line from that episode was that tetracaine appears safe for uncomplicated corneal abrasions and provides more effective pain relief than saline eye drops. We also did a critical appraisal of a systematic review by Swaminathan et al looking at topical anesthetics for these types eye injuries on SGEM#145. The SGEM bottom line from that review was that the best evidence we currently have demonstrates that dilute topical anesthetic drops of either proparacaine or tetracaine are safe for use in ED patients with simple corneal abrasions to provide analgesia. The studies are small, but the data contained in them is far superior to the case series published 50 years ago which led to the dogma that using them is dangerous. Clinical Question: What is the efficacy of topical tetracaine in the treatment of simple corneal abrasions? Reference: Shipman et al. Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Annals of EM 2020 Population: Adults 18 years to 80 years of age with suspected acute cornea abrasion Exclusions: Contact lens wearer, previous corneal surgery or transplant in the affected eye, injury greater than 36 hours old, had a grossly contaminated foreign body, or had coexisting ocular infection. Intervention: Tetracaine 0.5% one drop every 30 minutes as needed for pain for a maximum of 24 hours plus topical antibiotics (polymyxin B sulfate/ trimethoprim sulfate, two drops every four hours into the affected eye) and oral analgesic (hydrocodone/acetaminophen 7.5/325 mg, one or two tablets as needed every six hours) Comparison: Placebo (balanced artificial tear solution) one drop every 30 minutes as needed for pain for a maximum of 24 hours plus topical antibiotics (polymyxin B sulfate/ trimethoprim sulfate, two drops every four hours into the affected eye) and oral analgesic (hydrocodone/acetaminophen 7.5/325 mg, one or two tablets as needed every six hours) Outcome: Primary Outcome: Pain score using a numeric rating scale (NRS from 0-10) measured at the follow-up ED visit in 24-48 hours. Secondary Outcomes: Use of hydrocodone for breakthrough pain, and any adverse events. Authors’ Conclusions: “Short term tetracaine is effective for corneal abrasions.” 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). Yes The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure 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. Unsure The treatment effect was large enough and precise enough to be clinically significant. Yes Key Results: They enrolled 118 patients into the trial. The median age was in the mid 30’s and 60% were male. Baseline NRS for pain was 7 out of 10. Just over 10% had a metallic foreign body and more than ¼ had another foreign body. Topical tetracaine was highly effective in reducing pain from simple corneal abrasions. Primary Outcome: Pain on NRS (0-10) at 24 to 48 hour follow-up Tetracaine 1 vs. placebo 8, difference 7 (95% CI 6 to 8) Secondary Outcomes:  Amount of hydrocodone tablets ingested (1 vs. 7) Adverse events (4% vs 11%) 1) Ophthalmologists vs. EM Physicians: There has been a divide between these two specialties. Ophthalmologists probably have some selection bias because you see the worst cases or those that have had complications. This bias can be quantified in this trial. Only about 1 in 5 patients referred to ophthalmology actually attended the consultation one week after injury. Ophthalmologists have a potential selection bias (only referred patients) and treat abrasions differently than EM doctors. We use bandage contact lenses and virtually never prescribe opioids. This will be helpful in framing the discussion of this paper and discussing the motivation for EM physicians to find alternative ways of treating abrasions (ie. tetracaine over opioids) 2) Simple Corneal Abrasions: This is very important. They had a good list of exclusion criteria in the manuscript such as length of time until evaluation in the ED, other ocular infection, grossly contaminated foreign bodies, or other injuries. There were even more listed in exclusion criteria listed in ClinicalTrials.gov that included: “pregnancy, retained foreign body, penetrating eye injury, immunosuppression, allergy to study medication, inability to attend follow up, inability to fluently read and speak English or Spanish, or any injury requiring urgent ophthalmologic evaluation (large or complicated abrasions with significant vision loss, corneal ulcers, corneal lacerations).” Previous studies have excluded corneal injuries with foreign bodies. I liked that they only excluded ones that were “grossly contaminated”. More than 1/3 of the cohort did have either a metallic or some other foreign body. This expands the external validity of the study. Establishing the diagnosis of “simple abrasion” is critical when considering prescribing tetracaine, but unfortunately, the diagnosis is not always straight forward. Severe dry eye and exposure keratopathy is another thing that is often misdiagnosed as an abrasion in the ED. 3) Blinding: The authors correctly acknowledge that the study could have been unblinded for a couple of reasons. Anyone who has used tetracaine knows it comes with a very strong burning sensation. The packaging of the tetracaine (bottle) and placebo (four ampules) were different. They never did confirm with the patients that blinding was maintained by asking which group they thought they had been allocated to. It’s hilarious to think you can adequately mask a study like this because 20 minutes out the door, and the patient will absolutely know if they have saline or tetracaine. I’m more interested in the people who received saline but kept using it. Wishful thinking, I guess. Should we be even using the term “blinding” in a trial involving eye injuries? The lack of blinding could certainly have introduced a placebo effect, but this is usually about 2-3 points on the NRS. The decrease in pain in this trial was 6 points in the treatment group and a 7-point difference compared to the placebo group. So,

Date: January 5th, 2021 Reference: Grunau et al. Association of Intra-arrest Transport vs Continued On-Scene Resuscitation With Survival to Hospital Discharge Among Patients With Out-of-Hospital Cardiac Arrest. JAMA 2020 Guest Skeptic: Mike Carter is a former paramedic and current PA practicing in pulmonary and critical care as well as an adjunct professor of emergency medical services at Tacoma Community College. Case: During a busy emergency department (ED) shift the paramedic phone rings.  On the other end of the line is one of your local crews who have responded to a 54-year-old male with a witnessed cardiac arrest.  CPR is currently in progress with a single shock having been delivered.  The crew is asking if they should transport the patient with resuscitation ongoing? Background: Out-of-hospital cardiac arrest (OHCA) is something we have covered extensively on the SGEM over the years. This has included things like therapeutic hypothermia (SGEM#54, SGEM#82, SGEM#183 and SGEM#275), supraglottic devices (SGEM#247), crowd sourcing CPR (SGEM#143 and SGEM#306), and epinephrine (SGEM#238). One aspect we have not looked at is the “load and go” vs. “stay and play” approach for OHCA. Different countries have different approaches to this problem. There is the European model that is physician led and provides more care in the field while the North American model tends to scoop and run. However, there is a fair bit of heterogeneity between EMS systems even in the US. In patients with OHCA, some EMS agencies transport almost all patients regardless of ROSC, while others rarely transport if ROSC is not achieved. It is unclear from the existing literature which practice is superior to the other in providing patient-oriented benefit to among adult patients in refractory arrest who have suffered an OHCA. Clinical Question: What is the association of intra-arrest transport compare to continued on-scene resuscitation in regards to survival to hospital discharge in adult patients with an OHCA? Reference: Grunau et al. Association of Intra-arrest Transport vs Continued On-Scene Resuscitation With Survival to Hospital Discharge Among Patients With Out-of-Hospital Cardiac Arrest. JAMA 2020 Population: Adults 18 years and older with non-traumatic OHCA between 2011 and 2015treated by 192 EMS agencies in the USA. EMS. OHCA was defined as persons found apneic and without a pulse who underwent either external defibrillation (bystanders or EMS) or chest compressions. Exclusions: Age less than 18 years, do-not-resuscitate (DNR) order being discovered, transport prior to cardiac arrest, missing data to classify as intra-arrest or to classify the primary outcome, missing variables required for propensity score analysis Intervention: Intra-arrest transport prior to any episode of return of spontaneous circulation (ROSC) defined as palpable pulse for any duration Comparison: Continued on-scene resuscitation Outcome: Primary Outcome: Survival to hospital discharge Secondary Outcomes: Survival with favorable neurologic outcome defined as a modified Rankin scale (mRS) score of less than 3 mRS is categorized to 7 different levels, with 0 being no disability and 6 being death. A 3 is defined as moderate disability requiring some help, but able to walk without assistance Authors’ Conclusions: “Among patients experiencing out-of-hospital cardiac arrest, intra-arrest transport to hospital compared with continued on-scene resuscitation was associated with lower probability of survival to hospital discharge. Study findings are limited by potential confounding due to observational design.” Quality Checklist for Observational Study: Did the study address a clearly focused issue? Yes Did the authors use an appropriate method to answer their question? Yes Was the cohort recruited in an acceptable way? Yes Was the exposure accurately measured to minimize bias? Unsure Was the outcome accurately measured to minimize bias? Yes Have the authors identified all-important confounding factors? Unsure Was the follow up of subjects complete enough? Yes How precise are the results? Fairly precise  Do you believe the results? Yes [1,2] Can the results be applied to the local population? Unsure Do the results of this study fit with other available evidence? Yes [3,4] Key Results: The entire cohort consisted of 43,969 patients with a median age of 67 years, 1/3 were female and ½ were bystander or EMS witnessed. Of these OHCAs, 22% had an initial shockable rhythm and ¼ underwent intra-arrest transport. The probability of survival was greater with continuous on-scene resuscitation compared to intra-arrest transport in adults with OHCAs. 1) Association: The biggest limitation of study design is its observational nature. This means we can only conclude an association, not causation. Propensity score matching can help but is not able to eliminate unmeasured confounders that could bias the results. There were some details that should be explained about propensity matching. The initial cohort composed of greater than 57,000 patients with 13,756 were excluded due to a variety of reasons. In addition, only 18,812 underwent 1:1 propensity score matching (9,406 in each arm) with ~25,000 going unmatched.  Of these, 16,264 had no satisfactory match available. The end result is that it wasn’t 57,000 adult patients with OHCA whose propensity score were matched but rather less than 50% (9,406 intra-arrest transport and 18,299 on-scene resuscitation). These details are another reason why we need to be careful not to over-interpret the data that stay and play is superior to load and go.   2) Older Data: These results were based on older data from April 2011 to June 2015. This time frame was selected for a couple of reasons. Prior to April 2011, there were differences in data definition. Only including data from April 2011 forward minimizes this issue. The stop data of June 2015 was because the ROC registry was discontinued at that time. I do not think that older data would significantly impact the results of this study. We do not have been interventions that have demonstrated to have a patient-oriented outcome (POO) in patients with OHCA. There is the classic OPALS study by the Legend of EM Dr. Ian Steill on ACLS vs BLS (SGEM#64) showing no statistical difference in survival to hospital discharge (5.1% vs 5.0%).  We also mentioned things like pre-hospital therapeutic hypothermia, supraglottic devices, crowd sourcing CPR, epinephrine in the background section not resulting in a clinical benefit. The SGEM has also covered IV vs IO (SGEM#231) and amiodarone vs lidocaine (SGEM#162). Neither of these two studies were high-quality evidence demonstrating a superior strategy for a POO. It was ~2010 that the major emphasis towards high efficiency CPR started to get pushed in the prehospital arena.  ROC data has shown a gradual uptick in survival from OHCA, although this is in the realm of ~1% from 2011 - 2015 [5].  However, looking at CARES registry data there has been no change 3) Mechanical CPR: No data was presented on mechanical CPR utilization. There is some literature regarding better hemodynamics, chest compression fraction etc. with mechanical devices during transport. However, there is no evidence that mechanical CPR results in a POO. We covered this on SGEM#136 with REBEL EM and we even debated the issue at SMACC. That does not mean there could not be other benefits to mechanical CPR such as safety for EMS personnel. However, this claim would need to be demonstrated and is it any better than a special harness to secure paramedics while performing CPR in the back of the ambulance on transport. CPR has to be a bridge to somewhere. Adults patients with OHCA and non-shockable rhythms have a very poor prognosis. Prolonged CPR is associated with worse probability of survival with good neurologic outcome [6]. 4) Prognostication Bias: This is not a specific bias that we have discussed before in detail on the SGEM. However, we the discussed general idea of bias multiple times on the SGEM. I define bias as something that systematically moves us away from the “truth” (best point estimate of effect size). Prognostication bias is thought to have seven major domains for risk of bias in prognosis research. The seven major domains include: study participation, attrition, selection of candidate predictors, outcome definition, confounding factors, analysis, and interpretation of results [7]. The domain of prognostication bias recognized in this observational study by the authors was a potential for attrition bias. Those adult patients with OHCA and unfavorable phenotypes may (may not) have had resuscitation terminated early. This means they would not have the opportunity to achieve ROSC. They did document a difference in out-of-hospital termination of resuscitation. It was 0.2% of intra-arrest transport compared to 56.7% for the on-scene resuscitation for the full cohort. Similar results were observed in the propensity matched analysis. This could potentially have biased the results. 5) External Validity: We mentioned in the background material that different countries have either a physician led or non-physician led EMS system. There are even differences within countries whether or not policies exist to transport all patients depending on if ROSC is achieved.  This database was heterogenous because the medical care was carried out per local protocols, including decisions of hospital transport and termination of resuscitation. The local counties in my neck of the woods ascribe a significant degree of autonomy to our paramedics, with few protocols dictating a transport decision.  Most common are guidelines for ceasing efforts; such as PEA that remains refractory to all ALS procedures or persistent asystole.