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
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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:
Consider using the LUCCSASS mnemonic to remember occult sources of infection:
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
Most patients will be admitted, especially those who are septic, on fluoroquinolone prophylaxis, or those who have suspected antibiotic-resistant organisms
Some patients may be appropriate for discharge in consultation with an oncologist/infectious diseases specialist after antibiotics are given, and >4h observation
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!
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
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)
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)
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
Arany Z, Elkayam U. Peripartum Cardiomyopathy. Circulation. 2016 Apr 5; 133:1397–1409.
Honigberg MC , Givertz MM. Peripartum cardiomyopathy. BMJ. 2019 Jan 30; 364:k5287.
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:
Mucosal/skin involvement + airway involvement
Two system involvement
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)
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!
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
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
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.
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.
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.
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.
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)
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.
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
Dr. Anton Helman is an Emergency Physician at North York General in Toronto. He is an Assistant Professor at the University of Toronto, Division of Emergency Medicine and the Education Innovation Lead at the Schwartz-Reisman Emergency Medicine Instititute. He is the founder, editor-in-chief and host of Emergency Medicine Cases.