Journal Feed Weekly Wrap-Up

We always work hard, but we may not have time to read through a bunch of journals. It’s time to learn smarter. 
Originally published at JournalFeed, a site that provides daily or weekly literature updates. 
Follow Dr. Clay Smith at @spoonfedEM, and sign up for email updates here.

#1: When to Intubate ACEi Angioedema

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Rapid progression of symptoms within the first 6 hours of angioedema onset, anterior tongue swelling, vocal changes, drooling, and dyspnea were all high-risk features associated with need for intubation in patients with ACE inhibitor (ACEi) associated angioedema. Patients with isolated lip swelling were significantly less likely to require intubation.

Why does this matter?
ACE inhibitors are associated with 30-40% of all ED presentations for angioedema. ACEi associated angioedema most commonly affects the lips, tongue, and face, but the most feared complication is acute airway obstruction which can occur in up to 10% of cases. The mainstay of treatment is discontinuing the offending agent as well as supportive care with close airway monitoring. However, the real challenge is determining when patients require intervention to secure their airway.

Man, that face is swole!
This was a retrospective study of 190 patient encounters of ACEi associated angioedema over a 3-year period at a large, urban, tertiary referral emergency department. Overall, 18 patients (9.5%) required intubation. No patients required a surgical airway or other airway rescue device. Risk factors associated with need for intubation were rapid progression of symptoms within the first 6 hours of angioedema onset, anterior tongue swelling, vocal changes, drooling, and dyspnea. Isolated lip swelling occurred in 54% of cases, and patients with isolated lip swelling were significantly less likely to require intubation. These risk factors combined with your clinical gestalt can be used to risk stratify patients with ACEi associated angioedema in order to determine the best plan for management and disposition.

Emergency department evaluation of patients with angiotensin converting enzyme inhibitor associated angioedema. Am J Emerg Med. 2020 Dec;38(12):2596-2601. doi: 10.1016/j.ajem.2019.12.058. Epub 2020 Jan 7.

For more on angioedema, see this emDocs Cases post.

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 #2: TXA May Increase Mortality in TBI

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TXA given in the prehospital setting for isolated traumatic brain injury (TBI) was associated with increased 30-day mortality.

Why does this matter?
CRASH-2 showed lower mortality from bleeding in trauma patients. CRASH-3 showed a slight 28-day mortality benefit in TBI patients with a GCS ≥9, especially in the subgroup to whom TXA was given early. But a recent RCT showed no benefit when TXA was given early, in the prehospital setting, for patients with moderate to severe TBI. This study noted the RCT just mentioned included patients with both moderate and severe injury as well as extracranial injuries. So they are laser focused in this analysis on the impact of TXA on patients with severe TBI and isolated TBI.

TXA by EMS? No.
This was a retrospective look at prospectively collected data from BRAIN-PROTECT. This was a cohort of patients with severe TBI (GCS ≤8) who received prehospital treatment and were flown by helicopter to level 1 Dutch trauma centers. During the ~5-year period of the study, a variety of prehospital treatments were performed, which allowed them to compare cohorts while adjusting for confounders. In all, they included 1,827 patients; 1,375 had confirmed TBI; 719 had isolated TBI. Out of the entire cohort, 693 received TXA; TXA patients tended to be older and more severely injured. Unadjusted analysis showed increased 30-day mortality in the TXA group. However, with multiple logistic regression to adjust for confounders, there was no significant difference in 30-day mortality in the entire cohort or those with confirmed TBI. But in those with isolated TBI, they found a strong association with higher mortality (aOR 4.49, 95%CI 1.57-12.87). The figure shows it best. There is a balance between stopping bleeding and hypercoagulability. It looks like early, prehospital TXA for isolated TBI is probably not safe.

From cited article

From cited article

Association Between Prehospital Tranexamic Acid Administration and Outcomes of Severe Traumatic Brain Injury. JAMA Neurol. 2020 Dec 7. doi: 10.1001/jamaneurol.2020.4596. Epub ahead of print.

Spoon Feed
In this US-based cohort study, the emergency department (ED) discharge rate of acute pulmonary embolism (PE) was <5%. The rate of outpatient PE management varied widely between institutions.

Why does this matter?
Outpatient management of patients with deep venous thrombosis (DVT) has been more widely accepted as a best practice, while adoption of outpatient management of low-risk patients with acute PE has lagged(1-5). Outpatient management for patients deemed low-risk by validated clinical decision tools (PESI, sPESI, and Hestia Criteria) leads to safe, efficacious, patient-centered, and cost-effective care (6-12). This practice is simplified by the use of direct oral anticoagulant medications (DOACs) (13-15), and supported by clinical trial evidence (16-20) and clinical practice guidelines from international societies (21-26). @LWestafer, et al. shed further light on this US practice pattern…

Let us repeat the mantra together:  “Low-risk PEs may be discharged. Low-risk PEs may be discharged. Low-risk PEs may be discharged…”
This was a retrospective cohort of 61,070 adult patients diagnosed with acute PE in 740 US hospitals. The primary outcome was initial disposition from the ED – discharge from the ED versus admission to an inpatient or observation unit. The discharge rate of acute PE was <5%. At 30 days, 1.3% had a bleeding-associated diagnosis, and rates of return to the ED were similar to prior studies (17.9%) with only 10.3% hospitalized. Unsurprisingly, the cost of inpatient management was higher (to the tune of a median 6x higher) than those discharged from the ED. The rates of outpatient PE management varied widely between institutions, and the hospital where a patient presented was one of the strongest predictors of a patient being admitted or discharged.

Despite the large body of clinical trial evidence and the support of practice guidelines, clinicians remain wary of discharging patients with PE. Clinicians who practice in the acute care setting should continue to become comfortable with risk stratification, anticoagulation, and discharge of low-risk PE.

Another Spoonful
Check out our recent JournalFeed VTE week covering Outpatient PE Tx in the DOAC era from Maughan, et al.

Outpatient Management of Patients Following Diagnosis of Acute Pulmonary Embolism. Acad Emerg Med. 2020 Nov 28. doi: 10.1111/acem.14181.

Reviewed by Clay Smith

For more on pulmonary embolism and outpatient management, see this emDocs post

FOAMed links

Here are some other notable outpatient PE study discussions on FOAMed:

Works Cited

  1. Weeda ER, Butt S. Systematic Review of Real-World Studies Evaluating Characteristics Associated With or Programs Designed to Facilitate Outpatient Management of Deep Vein Thrombosis. Clin Appl Thromb Hemost 2018;24:301S-13S.

  2. Singer AJ, Thode HC, Jr., Peacock WFt. Admission rates for emergency department patients with venous thromboembolism and estimation of the proportion of low risk pulmonary embolism patients: a US perspective. Clin Exp Emerg Med 2016;3:126-31.

  3. Fang MC, Fan D, Sung SH, et al. Outcomes in adults with acute pulmonary embolism who are discharged from emergency departments: the Cardiovascular Research Network Venous Thromboembolism study. JAMA Intern Med 2015;175:1060-2.

  4. Vinson DR, Ballard DW, Huang J, et al. Outpatient Management of Emergency Department Patients With Acute Pulmonary Embolism: Variation, Patient Characteristics, and Outcomes. Annals of emergency medicine 2018;72:62-72 e3.

  5. Westafer LM, Shieh MS, Pekow PS, Stefan MS, Lindenauer PK. Outpatient Management of Patients Following Diagnosis of Acute Pulmonary Embolism. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 2020.

  6. Aujesky D, Obrosky DS, Stone RA, et al. Derivation and validation of a prognostic model for pulmonary embolism. American journal of respiratory and critical care medicine 2005;172:1041-6.

  7. Jimenez D, Aujesky D, Moores L, et al. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010;170:1383-9.

  8. Zondag W, Mos IC, Creemers-Schild D, et al. Outpatient treatment in patients with acute pulmonary embolism: the Hestia Study. Journal of thrombosis and haemostasis : JTH 2011;9:1500-7.

  9. Zhou XY, Ben SQ, Chen HL, Ni SS. The prognostic value of pulmonary embolism severity index in acute pulmonary embolism: a meta-analysis. Respir Res 2012;13:111.

  10. Yamashita Y, Morimoto T, Amano H, et al. Validation of simplified PESI score for identification of low-risk patients with pulmonary embolism: From the COMMAND VTE Registry. Eur Heart J Acute Cardiovasc Care 2020;9:262-70.

  11. Wells P, Peacock WF, Fermann GJ, et al. The value of sPESI for risk stratification in patients with pulmonary embolism. Journal of thrombosis and thrombolysis 2019;48:149-57.

  12. Donze J, Le Gal G, Fine MJ, et al. Prospective validation of the Pulmonary Embolism Severity Index. A clinical prognostic model for pulmonary embolism. Thrombosis and haemostasis 2008;100:943-8.

  13. Roy PM, Corsi DJ, Carrier M, et al. Net clinical benefit of hospitalization versus outpatient management of patients with acute pulmonary embolism. Journal of thrombosis and haemostasis : JTH 2017;15:685-94.

  14. Kahler ZP, Beam DM, Kline JA. Cost of Treating Venous Thromboembolism With Heparin and Warfarin Versus Home Treatment With Rivaroxaban. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 2015;22:796-802.

  15. Fanikos J, Rao A, Seger AC, Carter D, Piazza G, Goldhaber SZ. Hospital costs of acute pulmonary embolism. Am J Med 2013;126:127-32.

  16. Vinson DR, Mark DG, Chettipally UK, et al. Increasing Safe Outpatient Management of Emergency Department Patients With Pulmonary Embolism: A Controlled Pragmatic Trial. Ann Intern Med 2018;169:855-65.

  17. Kline JA, Kahler ZP, Beam DM. Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance. Patient Prefer Adherence 2016;10:561-9.

  18. Bledsoe JR, Woller SC, Stevens SM, et al. Management of Low-Risk Pulmonary Embolism Patients Without Hospitalization: The Low-Risk Pulmonary Embolism Prospective Management Study. Chest 2018;154:249-56.

  19. Frank Peacock W, Coleman CI, Diercks DB, et al. Emergency Department Discharge of Pulmonary Embolus Patients. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine 2018;25:995-1003.

  20. Barco S, Schmidtmann I, Ageno W, et al. Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial. European heart journal 2020;41:509-18.

  21. Mazzolai L, Aboyans V, Ageno W, et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function. European heart journal 2018;39:4208-18.

  22. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS): The Task Force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Respir J 2019;54.

  23. Howard L, Barden S, Condliffe R, et al. British Thoracic Society Guideline for the initial outpatient management of pulmonary embolism (PE). Thorax 2018;73:ii1-ii29.

  24. American College of Emergency Physicians Clinical Policies Subcommittee on Thromboembolic D, Wolf SJ, Hahn SA, et al. Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Suspected Acute Venous Thromboembolic Disease. Annals of emergency medicine 2018;71:e59-e109.

  25. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016;149:315-52.

  26. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e419S-e96S.

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#3: Prednisone to Reduce Cluster Headaches

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Prednisone, given while up-titrating verapamil, was effective at reducing the frequency of cluster headache attacks.

Why does this matter?
Prednisone is often used for cluster headache, but its effectiveness hasn’t been proven in a RCT. Even one less cluster headache could impact quality of life. Does prednisone reduce cluster headache attacks?

Cluster bomb, cluster headache, cluster B…the only good cluster I know is a Goo Goo Cluster (…pecan is the best).
This was a multicenter, double blinded, placebo controlled RCT with 116 patients who received prednisone 100mg x 5 days, with a taper by 20mg every three days (17 days total) or placebo while up-titrating verapamil for prophylaxis (40mg tid up to 120mg tid over 19 days). Mean number of attacks in the first week were fewer in the prednisone group vs placebo: 7.1 vs 9.5, respectively (-2.4 headache attacks, 95%CI -4.8 to -0.03). Also, 35% of the prednisone group vs. 7% (p=0.0006) of placebo patients had complete cessation of attacks in the first 7 days. There was no increase in serious adverse events in the treatment arm. There were a number of exclusions you should be aware of and consider, such as diabetes, hypertension, gastric ulcers, along with many others. They had to stop the trial early because it was difficult to enroll patients, and they ran out of funding. Almost all patients enrolled were German, which may impact generalizability. Overall, this is an evidence based treatment that could help patients suffering with this awful condition.

Safety and efficacy of prednisone versus placebo in short-term prevention of episodic cluster headache: a multicentre, double-blind, randomised controlled trial. Lancet Neurol. 2021 Jan;20(1):29-37. doi: 10.1016/S1474-4422(20)30363-X. Epub 2020 Nov 24.

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