Topics in this EM Quick Hits podcast

Ken Milne on The 10 Best EM Papers of 2021 (00:40)

Brit Long on a careful structured approach to Febrile Neutropenia to improve outcomes (11:55)

Catherine Varner on how not to miss Peripartum Cardiomyopathy (20:35)

Joe Nemeth on Anaphylaxis Update (27:30)

Anand Swaminathan on his approach to The Crashing Asthmatic (38:54)

Podcast production, editing and sound design by Anton Helman

Podcast content, written summary & blog post by Kate Dillon and Joe Nemeth, edited by Anton Helman, January 2022

Cite this podcast as: Helman, A, Milne, K, Varner, C, Long, B, Nemeth, J, Swaminathan, A. EM Quick Hits 35 – 10 Best Papers of 2021, Peripartum Cardiomyopathy, Crashing Asthmatic, Febrile Neutropenia, Anaphylaxis update. January, 2022. https://emergencymedicinecases.com/em-quick-hits-january-2022/Accessed [date].

10 Best EM Papers of 2021 from EM Cases Summit 2021

1. TTM2 – Therapeutic Hypothermia after Cardiac Arrest

  • Population: adult patients with out of hospital cardiac arrest who were comatose
  • Intervention: cooled to 33°C vs. maintaining normothermia
  • Primary Outcome: all-cause mortality at 6 months
  • Results: no statistical difference between groups (~50% in both groups)

Bottom line: no benefit to cooling patients after out of hospital cardiac arrest who are comatose

Deep dive: https://thesgem.com/2021/07/sgem336-you-cant-always-get-what-you-want-ttm2-trial/

Deep dive into worlds literature on therapeutic hypothermia: Journal Jam on Therapeutic Hypothermia after Cardiac Arrest

2. SALSA Trial – Hypertonic Saline to treat Hyponatremia

  • Population: adult patients with sodium <126 mmol/L and moderate to severe symptoms
  • Intervention: rapid intermittent bolus strategy vs. slow continuous infusion strategy
  • Primary Outcome: incidence of overcorrection of serum sodium up to 48 hours
  • Results: no statistical difference between groups

Bottom line: speed of correction does not matter, but be careful not to overcorrect the sodium

Deep Dive: https://thesgem.com/2021/04/sgem326-the-salsa-study-hypertonic-saline-to-treat-hyponatremia/

3. tPA before endovascular therapy for stroke

  • Population: adult patients within 4.5 hours of onset of symptoms
  • Intervention: tPA + EVT within 30 minutes vs. EVT alone
  • Primary Outcome: modified Rankin Scale (mRS – a scale for neurologic disability) at 90 days
  • Results: no statistical difference in modified Rankin Scale, or all-cause mortality between groups, however there was more bleeding in the combination group (tPA + EVT)

Bottom line: no high-quality evidence to support tPA before EVT, if EVT is readily available

Deep dive: https://thesgem.com/2021/06/sgem333-do-you-gotta-be-starting-something-like-tpa-before-evt/

4. NoPAC Trial – TXA for epistaxis

  • Population: adult patients with persistent atraumatic epistaxis after local pressure/ice to the bridge of the nose for 10 minutes AND topical vasoconstrictor for 10 minutes
  • Intervention: topical TXA (200mg) for 10 minutes with pressure vs. sterile water for 10 minutes with pressure
  • Primary Outcome: use of anterior nasal packing during the index ED visit
  • Results: no statistical difference in patients getting anterior packing between TXA and placebo

Bottom line: the evidence on the efficacy of TXA in epistaxis is inconsistent

Deep dive: https://thesgem.com/2021/03/sgem321-the-times-they-are-a-changin-for-txa-in-epistaxis/

Deep dive into the literature on TXA for all indications: Journal Jam 18: The Evidence for TXA

5. SAFER Trial- Pediatric CAP antibiotics duration of therapy

  • Population: children 6mo – 10yr diagnosed with CAP, well enough for outpatient management
  • Intervention: 5 days of high dose amoxicillin (90mg/kg/day, divided TID) then 5 days of placebo vs. 10 days of high dose amoxicillin (90mg/kg/day, divided TID)
  • Primary Outcome: clinical cure at 14-21 days
  • Results: no statistical difference between the two groups (however, the lower end of their confidence interval was greater than their pre-determined boundary of 7.5%, so cannot formally claim non-inferiority)

Bottom line: consider shared decision making with parents regarding 5 vs. 10 days of antibiotics in pediatric CAP

Deep dive: https://thesgem.com/2021/07/sgem338-are-children-with-cap-safe-and-sound-if-treated-for-5d-rather-than-10d-of-antibiotics/

6. Pink lady for epigastric pain

  • Population: adult patients with epigastric pain or dyspepsia presenting to the ED
  • Intervention: oral viscous lidocaine (10mL 2% viscous gel) and antacid (10mL) vs. oral lidocaine solution (10mL 2% solution) and antacid (10mL) vs. antacid (20mL) alone
  • Primary Outcome: change in pain score on 100mm visual analog scale 30min after treatment
  • Results: no statistical difference between the three treatment groups

Bottom line: consider using antacid monotherapy for patients with dyspepsia in the ED

Deep dive: https://thesgem.com/2020/09/sgem302-we-didnt-start-the-fire-but-can-antacid-monotherapy-stop-the-fire/

7. Physician weight bias

  • Population: practicing EM staff physicians and residents in North America
  • Intervention: survey instruments measuring implicit weight bias (IWB), explicit weight bias (EWB), and professional weight bias (PWB)
  • Primary Outcome: descriptive analyses along with correlative models
  • Results: a high percentage of participants indicated IWB against other physicians, other results suggested some EWB and PWB exists

Bottom line: recognize that weight bias exists in medicine, understand how to overcome these biases, and mitigate negative impacts on patient care and physician to physician relationships

Deep dive: https://thesgem.com/2021/09/sgem343-doctors-are-doctors-so-why-should-it-be-you-and-i-should-get-along-so-awfully-weight-bias-in-medicine/

8. Immediate vs delayed cath lab for NSTEMI

  • Population: adults with out of hospital cardiac arrest who got ROSC with no ST-segment elevation on ECG
  • Intervention: immediate angiography vs. delayed or selective angiography
  • Primary Outcome: all-cause mortality at 30 days
  • Results: no statistical difference in all-cause mortality at 30 days

Bottom line: there appears to be no clinical  benefit to take out of hospital cardiac arrest patients with ROSC and no ST segment elevation on ECG immediately for angiography

Deep dive: https://thesgem.com/2021/09/sgem344-we-willwe-will-cath-you-but-should-we-after-an-ohca-without-st-elevations/

9. Infant fever workup AAP Guidelines

  • Population: well appearing, term infants between 8-60 days with a fever
  • Guideline Summary (from SGEM):

Bottom Line: these AAP guidelines have the potential to decrease the number of lumbar punctures, hospitalizations, and antibiotic treatment in well-appearing, febrile infants but do not replace clinician judgement, so consider the risk tolerance and aversion of the clinician and family when implementing these recommendations

Deep dive: https://thesgem.com/2021/08/sgem341-are-the-aap-guidelines-for-the-evaluation-and-management-of-the-well-appearing-febrile-infant-the-answer-to-a-never-ending-story/

10. HALT-IT – TXA for GI Bleeds

  • Population: adult patients with significant upper or lower GI bleed
  • Intervention: IV TXA (1g loading dose over 10 min, then 3g maintenance infusion over 24h) vs. matching placebo (sodium chloride 0.9% IV)
  • Primary Outcome: death due to GI bleeding within 5 days
  • Results: no statistically significant difference in mortality from GI bleed within 5 days or in all-cause mortality, statistically significant increase in VTE (double) in the TXA group

Bottom line: the latest evidence does not support the use of TXA in GI bleeds

Deep dive: https://thesgem.com/2020/09/sgem301-you-cant-stop-gi-bleeds-with-txa/

Deep dive into the literature on TXA: Journal Jam 18: The Evidence for TXA

For full access to the EM Cases Summit 2021  talks, procedural videos, rants and panel discussions visit emcasessummmit.com

  1. Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, et al. Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest. NJEM. 2021 Jun 17; 384:2283-2294.
  2. Baek SH, Jo YH, Ahn S, Medina-Liabres K, Oh YK, Lee JB, Kim S. Risk of Overcorrection in Rapid Intermittent Bolus vs Slow Continuous Infusion Therapies of Hypertonic Saline for Patients With Symptomatic Hyponatremia: The SALSA Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1; 181(1):81-92.
  3. Suzuki K, Matsumaru Y, Takeuchi M, Morimoto M, Kanazawa R, Takayama Y, et al. Effect of Mechanical Thrombectomy Without vs With Intravenous Thrombolysis on Functional Outcome Among Patients With Acute Ischemic Stroke: The SKIP Randomized Clinical Trial. JAMA. 2021 Jan 19;325(3):244-253.
  4. Zi W, Qiu Z, Li F, Sang H, Wu D, Luo W, Liu S, et al. Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial. JAMA. 2021 Jan 19; 325(3):234-243.
  5. Reuben A, Appelboam A, Stevens KN, Vickery J, Ewings P, et al. The Use of Tranexamic Acid to Reduce the Need for Nasal Packing in Epistaxis (NoPAC): Randomized Controlled Trial. Annals of Emergency Medicine. 2o21 Jun; 77(6):631-640.
  6. Pernica JM, Harman S, Kam AJ, Carciumaru R, Vanniyasingam T, et al. Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia: The SAFER Randomized Clinical Trial. JAMA Pediatr. 2021 May 1;175(5):475-482.
  7. Warren J, Cooper B, Jermakoff A, Knott JC. Antacid monotherapy is more effective in relieving epigastric pain than in combination with lidocaine. A randomized double-blind clinical trial. AEM. 2020 Jun 29; 27(9): 905-909.
  8. McLean ME, McLean LE, McLean-Holden AC, et al. Interphysician weight bias: A cross-sectional observational survey study to guide implicit bias training in the medical workplace. AEM. 2020 Apr 29; 28(9): 1024-1034.
  9. Desch S, Freund A, Akin I, Behnes M, et al. Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation. NEJM. 2021 Dec 30; 385: 2544-2553.
  10. Pantell RH, Roberts KB, Adams WG, Dreyer BP, Kuppermann N, et al. Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics. 2021 Aug;148(2):e2021052228.
  11. Roberts I, Shakur-Still H, Afolabi A, Akere A, et al. Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial. The Lancet. 2020 Jun 20; 395 (10241) 1927-1936.

Febrile neutropenia: A careful structured approach is important to improve outcomes

Diagnostic Criteria:

    • Fever: single oral temperature of >38.3°C OR >38.0°C for 1h with neutropenia
    • Neutropenia: most common 5-14 days after chemotherapy, defined as an absolute neutrophil count (ANC) < 0.50 × 109/L or < 1 × 109/L with expected decrease to < 0.50 × 109/L
    • Patients not meeting diagnostic criteria (borderline): consult your oncologist/internist, these patients are still at risk for poor outcomes!

Identifying a Source:

    • Most common sources: lung, urinary tract, GI, bloodstream, skin, but remember a reduced inflammatory response in neutropenic patients can mean the signs are subtle
    • Be aware of atypical infections/sites seen in immunocompromised patients such as:
      • ENT: mucositis, murcormycosis, malignant otitis externa
      • Abdomen: necrotizing enterocolitis (typhlitis) – look for abdominal pain N/V/D, peritonitis
      • Cardiac: endocarditis – look for a new murmur
      • Vascular devices
      • Perirectal: visually inspect the area
    • Consider using the LUCCSASS mnemonic to remember occult sources of infection:

Sources of Infection LUCCAASS Mnemonic

Antimicrobials: follow your local/institutional guidelines for antimicrobial coverage, but general principles can include:

    • Pseudomonal coverage for all patients (monotherapy is as effective as dual therapy)
    • Consider viral and/or fungal coverage (especially in typhlitis, or those who are still febrile despite 4 days of antibiotics)
    • MRSA coverage isn’t required for all patients but should be considered if: known history of MRSA, soft tissue infection, patients on fluoroquinolone prophylaxis, severe pneumonia, bloodstream infection, mucositis, line infection, hemodynamic instability /critically ill

Disposition:

Pitfall: although most patients on chemotherapy with a fever have an infection do not forget to consider tumor burden/necrosis, drug/transfusion reactions and PEs!

Clinical Pearl: remember, patients are often on steroids, so consider stress dose steroids in these patients

=> Bottom Line: watch out for occult signs of infection in patients who are febrile and on chemotherapy, consider using the LUCCAASS mnemonic when thinking about possible sources, remember to check your local antibiogram and discuss these cases with your oncologist and infectious diseases specialists, and finally remember to think about other causes of fever in cancer patients!

Review common oncologic emergencies with the Rapid Review Videos: Oncologic Emergencies

  1. Long B, Targonsky E, Brém E. Just the facts: febrile neutropenia in the emergency department setting. CJEM. 2021 Jul;23(4):445-449.

Peripartum cardiomyopathy – easily missed 

Clinical presentation: 

    • 3rd trimester or postpartum period
    • Shortness of breath out of proportion to dyspnea on exertion associated with pregnancy (this is one of the reasons peripartum cardiomyopathy is missed, as the shortness of breath is attributed to either pregnancy itself or PE)
    • Worsening lower extremity edema (edema is also common in normal pregnancies and so this is also easy to overlook)

Diagnostic considerations:

    • Bloodwork: D-Dimer, BNP (sensitive and specific for peripartum cardiomyopathy), Troponin
      • Note: making a diagnosis of peripartum cardiomyopathy does not preclude a diagnosis of PE, in fact these patients are at higher risk than the average patient, still need consider CTPA to rule out a PE
    • Imaging: start with a CXR in patients who are dyspneic prior to CT, you may be surprised by a pneumothorax or help confirm the diagnosis with the finding of pulmonary edema

Management (same as other patients with acute heart failure as described in Episode 163 and cardiogenic shock Episode 164)

Disposition:

    • Involve cardiology
    • Consider transfer to a tertiary care center
    • Recurrence: patients will likely be advised not to consider not conceiving again because their risk of recurrence is high and mortality is 2% in North America

=> Bottom Line: look out for signs of heart failure in women in the peripartum period who present with shortness of breath, consider using a BNP as screening bloodwork, and be aware that these patients are at an even higher risk for PEs

  1. Arany Z, Elkayam U. Peripartum Cardiomyopathy. Circulation. 2016 Apr 5; 133:1397–1409.
  2. Honigberg MC , Givertz MM. Peripartum cardiomyopathy. BMJ. 2019 Jan 30; 364:k5287.
  3. Egan DJ, Bisanzo MC, Hutson HR. Emergency department evaluation and management of peripartum cardiomyopathy. The Journal of Emergency Medicine. 2009 Feb: 36(2): 141-147.

Anaphylaxis update: there are specific indications for steroids, epinephrine is often under-dosed, IV epinephrine may be better than IM and the myth of iodine allergy

Diagnosis: clinical, 3 criteria:

    1. Mucosal/skin involvement + airway involvement
    2. Two system involvement
    3. Shock post exposure
      • NOTE: anaphylaxis should be diagnosed if the patient has isolated signs of hypotension, stridor, or bronchospasm after an exposure to known or potential allergen, even in the absence of skin involvement

Mechanism by which Anaphylaxis kills:

    • Airway: upper airway obstruction
    • Breathing: lower airway obstruction
    • Circulation: distributive shock, hypovolemic (via third spacing), cardiogenic shock (Kounis syndrome: cardiac ischemia from vasospasm and pro-inflammatory effects on the myocardium)

Treatment:

    • IM Epinephrine: 0.01mg/kg of 1:1000 epinephrine (max 0.5mg per dose) in the thigh (do not underdose!)
    • IV Epinephrine: consider at the onset, it has faster onset (seconds), smoother pharmacokinetics, and is easier to titrate, repeat dose, and taper
    • Epinephrine Resistant Anaphylaxis (0.3% of anaphylaxis cases):
      • Respiratory symptoms (stridor/wheeze) refractory to first dose epinephrine, consider nebulized epinephrine for the stridor, and nebulized salbutamol for the bronchospasm/wheeze, get help early!
      • Circulatory compromise – guided by PoCUS, consider alpha agonists, vasopressin, methylene blue, glucagon, isoproterenol
    • Steroids, H1/H2 Blockers: no good evidence for meaningful improvement in important outcomes, including rate of biphasic reactions, steroids should never replace epinephrine in anaphylaxis, but should be considered in:
      • Anaphylaxis + uncontrolled asthma
      • Anaphylaxis + shock
      • Anaphylaxis requiring ongoing treatment after 2 adequate doses of epinephrine.
      • Downside to steroids? Observational data from the Canadian C-CARE registry suggests an association with pre-hospital steroid treatment and hospitalization/admission to ICU
    • Biphasic Reactions: occurs 5% of the time, hours to up to 7 days later, risk factors include:
      • Requiring more than one epinephrine dose
      • Early symptom onset from exposure
      • Late treatment initiation
      • Underlying severe asthma
      • History of severe reactions
    • Discharging Patients
      • Observation: 1-2 hours after the resolution of symptoms in low risk, reliable patients (no evidence for the traditional “6-hour rule”)
      • Discharge Instructions: what to give (prescription for epinephrine injector), how to give it (IM, thigh) and when to give it (earliest sign of anaphylaxis)

Pitfall: a note on iodine allergies; it is felt that it is not the iodine leading to anaphylaxis, but rather the hyperosmolarity of the contrast agent compared to blood, and formulations that are lower in osmolarity have shown decreased incidence of anaphylaxis, evidence is lacking for the routine use of antihistamines or glucocorticoid premedication in these lower osmolarity contrast agents

=>Bottom Line: recognize the disease, use epinephrine early, consider IV epinephrine for smoother pharmacokinetics,  limitations/downsides of steroids and who to use steroids in, consider early discharge for the appropriately risk-stratified patient

Review Anaphylaxis and Anaphylactic Shock with these Rapid Review Videos

Other FOAMed resources on anaphylaxis

EMCrit How to use IV epinephrine for anaphylaxis

  1. Shaker MS, Wallace DV, Golden DBK, Oppenheimer J, et al. Anaphylaxis-a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol. 2020 Apr; 145(4):1082-1123.
  2. Dodd A, Hughes A, Sargant N, Whyte AF, Soar J, Turner PJ. Evidence update for the treatment of anaphylaxis. Resuscitation 2021 Jun 01; 163: 86-96.
  3. Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, Geller M, Gonzalez-Estrada A, Greenberger PA, Sanchez Borges M, Senna G, Sheikh A, Tanno LK, Thong BY, Turner PJ, Worm M. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020 Oct 30;13(10):100472.
  4. Patel N, Chong KW, Yip AYG, Ierodiakonou D, Bartra J, Boyle RJ, Turner PJ. Use of multiple epinephrine doses in anaphylaxis: A systematic review and meta-analysis. J Allergy Clin Immunol. 2021 Nov;148(5):1307-1315.
  5. Højlund S, Søe-Jensen P, Perner A, Bestle MH, Carl P, Thormar K, Viggers S, Elberling S, Garvey LH. Low Incidence of Biphasic Allergic Reactions in Patients Admitted to Intensive Care after Anaphylaxis. Anesthesiology. 2019 Feb; 130:284–291.

The crashing asthmatic: an approach using NIPPV, fluids, epinephrine and magnesium

For those patients who are not responding to first line therapies, use the following strategies to try and avoid intubation and maximize pre-intubation parameters:

  • Non-Invasive Ventilation (CPAP, BPAP): to support respiratory effort as tiring can lead to poor ventilation, hypercapnia, acidemia, and eventually hypoxemia and encephalopathy
    • Maximize inspiratory pressures to relax the muscles and help them recover
    • Consider ketamine to facilitate non-invasive ventilation
  • Fluid Bolus: 20-30cc/kg, these patients have lots of insensible loses and need adequate preload, especially for non-invasive ventilation strategies
  • Epinephrine: many of these patients are broncho constricted, the inhaled beta agonists are not getting into the lungs; reasonable to start with the same IM dose as anaphylaxis ~0.5mg IM, or IV 5-10 ug/min and titrate to effect
  • Magnesium: evidence is not great for the use of magnesium in asthma, however for these crashing patients think about giving higher doses (4g) and setting up an infusion (4g/hour) for 2 hours, magnesium can also help combat the tachy-dysrhythmias associated with epinephrine

=>Bottom Line: in the crashing asthmatic start NIPPV and consider using ketamine to facilitate this for patients who are encephalopathic or not tolerating it; use epinephrine IM or IV (5-10ug/min) to help reverse bronchoconstriction and allow inhaled beta agonists to get into the lungs; consider fluid bolus of 20-30cc/kg to help support preload especially if you need to intubate or use NIPPV and finally, consider using higher doses of magnesium (4g)

Dr. Mike Betzner’s approach at EMU 2020 on the Crashing Asthmatic

  1. Salim Rezaie, “REBEL Cast Episode 11: The Crashing Asthmatic”, REBEL EM blog, June 1, 2015. Available at: https://rebelem.com/rebelcast-crashing-asthmatic/.
  2. Lim WJ, Mohammed Akram R, Carson KV, Mysore S, Labiszewski NA, Wedzicha JA, Rowe BH, Smith BJ. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database Syst Rev. 2012 Dec 12;12:CD004360.
  3. Cydulka R et al. The use of epinephrine in the treatment of older adult asthmatics. Ann Emerg Med. 1988; 17(4): 322-6.

None of the authors have any conflicts of interest to declare