Landmark trial

EMCC Emergency Medicine Chula Conference I will survive with new evidences…. Trials that will change your ER practice…forever

Improving survival in major trauma and traumatic brain injury with an old drug, but new trick

Initial treatment in trauma 1 Liter of Early blood transfusion “Tranexamic acid” crystalloid ATLS 10th edition

ATLS 10th edition and TXA

- Competitive inhibitor of plasminogen activation - Noncompetitive inhibitor of plasmin. - Stabilization of clot J Thromb Haemost, 2010;8;1919-25,

Tranexamic acid (1g over 10 min stat and 1g over 8h given) within 3h of trauma safely reduced the risk of death in significant bleeding trauma patients Lancet. 2010;376:23-32.

Adults with TBI who were within 3 h of injury had - a Glasgow Coma Scale (GCS) score of 12 or lower - any intracranial bleeding on CT scan - no major extracranial bleeding Tranexamic acid 1g over 10 min stat and 1g over 8h) VS placebo Lancet 2019 Oct 14; [e-pub]. (https://doi.org/10.1016/S0140-6736(19)32233-0)

CRASH-3 trial Isolated TBI in 3 hours Tranexamic acid Placebo (1g over 10 min stat and 1g over 8h) N = 4613 N = 4514 Lancet 2019 Oct 14; [e-pub]. (https://doi.org/10.1016/S0140-6736(19)32233-0)

CRASH-3 trial Tranexamic acid Placebo Excluding GCS of 3 or bilateral non-reactive pupils Death 12.5% Death 14.0% RR = 0.89 (95% CI 0.80-1.00) Lancet 2019 Oct 14; [e-pub]. (https://doi.org/10.1016/S0140-6736(19)32233-0)

CRASH-3 trial Lancet 2019 Oct 14; [e-pub]. (https://doi.org/10.1016/S0140-6736(19)32233-0)

CRASH-3 trial Lancet 2019 Oct 14; [e-pub]. (https://doi.org/10.1016/S0140-6736(19)32233-0)

CRASH-3 trial • NNT in mild-to- Caution!! moderate head injury = 58 patients -True benefit may depend on faster hospital arrival • Total drug cost = time other than drug 250 mg/vial x 8 vials alone. = 500 บาทได้ทอน -Do not delay hospital delivery

How this can change our practice… •Tranexamic acid given within 3 h of injury safely reduces head injury-related deaths in patients with TBI. • Patients with GCS less than 8 (severe TBI) or non- reactive pupils are unlikely to benefit from tranexamic acid treatment. ยงิ่ ใหเ้ รว็ ยงิ่ มปี ระโยชน!์ !! Prehospital treatment?? Lancet 2019 Oct 14; [e-pub]. (https://doi.org/10.1016/S0140-6736(19)32233-0)

Case vignette A) Continue 10 L non-rebreathing mask. A 65-yo female patient with history of diabetic B) De-escalation to 5 L cannular O2 cardiomyopathy and C) High-flow cannular O2 recurrent CHF presented in D) Endotracheal intubation the ED with increase SOB for E) BiPAP ventilation 3 days. She was in breathing distress with RR 28/minute. RA SaO2 was 90% with raising up to 98% with 10 L non-rebreathing mask, but still tachypnic. Her PaCO2 was 30 mmHg. Diagnostic tests revealed that she had acute exacerbation of CHF. Besides standard care, what is your management to increase chance of hospital mortality, regarding the breathing therapy?

ESC guideline, Eur Heart J 2016 37:2129

Circulation 2013; 128:e240 Circulation 2017; 136:e137

16.4% and 15.2% OR 0.92 (95% CI, 0.64 to 1.31) Significant improvement in 1-hour pH and PaCO2 N Engl J Med. 2008;359:142-51.

Cochrane Database Syst Rev. 2019 Apr 5;4:CD005351. doi: 10.1002/14651858.CD005351.pub4.

- Meta-analysis critical review -Blinded or unblinded randomized controlled trials in adults with acute cardiogenic pulmonary edema - 24 RCTs included Cochrane Database Syst Rev. 2019 Apr 5;4:CD005351. doi: 10.1002/14651858.CD005351.pub4.

Cochrane Database Syst Rev. 2019 Apr 5;4:CD005351. doi: 10.1002/14651858.CD005351.pub4.

NIPPV may benefit on mortality in patients with hypocarbia PaCO2 > 45 mmHg

ET tube rate: NPPV vs Standard care

ET tube rate: More benefit in hypocarbia PaCO2 > 45 mmHg Cochrane Database Syst Rev. 2019 Apr 5;4:CD005351. doi: 10.1002/14651858.CD005351.pub4.

How this can change our practice… • NIPPV reduces the hospital mortality and the chance of ET intubation in adult patients with ACPE. • More pronounced benefits in patients with normo/hypocarbia.

Case vignette You were in the cafeteria for A) Finger sweep for FB a cup of afternoon coffee. A removal middle-age man collapsed when having his lunch in B) Head tilt/chin lift for airway front of you and his family. opening He was gasping with mouthful of food. Definite C) Standard CPR with 30:2 pulse was uncertain. provision of ventilation After calling for help and activating EMS team, all D) Compression-only CPR alone without any assisting device or other rescuer, what will you do next? E) Head tilt to left side to prevent regurgitation

How reasonable is reasonable?

• Large observational nationwide study • Bystander witnessed 30445 OHCA patients Circulation. 2019 doi: 10.1161/CIRCULATIONAHA.118.038179.

Chance of 30-day survival • NO CPR 12186 • Standard CPR 11920 • CO-CPR 6339 Circulation. 2019 doi: 10.1161/CIRCULATIONAHA.118.038179.

EMS response time matters…. Circulation. 2019 doi: 10.1161/CIRCULATIONAHA.118.038179.

How this can change our practice… Endorsement of CO-CPR in Regurgitation/emesis in public layperson bystanders ¼ of prehospital CA1,2 1. J Intern Med. 2006;260:39-42. 2. Resuscitation. 2007;74:427-31.

First, do no harm. -Hippocrates Second, do some good. -Anne M. Lipton, M.D., Ph.D. Thank you!! Q&A (Please..)