More trials from TBS 2025. (part 2)

By / / #FOAMed, Critical Care, Emergency Medicine, Major Trauma, Prehospital Care, Research, Resuscitation

My previous post looked at the papers I presented in the EBM session at TBS. You can see that post here. Today we have brief links to the papers presented by Brian Burns (Sydney HEMS) and Rob McSweeney (Critical care reviews). I’ve kept the list short and snappy, and as always if you want. to know more please read and interpret the papers yourself. Don’t believe everything you read on a blog!

HEMOTION – Liberal vs. Restrictive Transfusion in TBI

🔎 Question: Does a liberal transfusion strategy (Hb ≤10g/dL) improve outcomes compared to a restrictive strategy (Hb ≤7g/dL) in moderate or severe traumatic brain injury (TBI)?

đź“Š Key Findings:

  • No significant difference in neurological outcomes at 6 months.
  • Similar rates of venous thromboembolism (VTE).
  • Increased ARDS risk in the liberal transfusion group (3.3% vs. 0.8%).

🧪Study Strengths & Limitations:

  • Strengths: Large multicenter RCT, robust methodology, strong follow-up data.
  • Limitations: Generalizability may be limited to well-resourced neurocritical care centers.

đź’ˇ Bottom Line:
No evidence that liberal transfusion improves outcomes—restrictive transfusion remains reasonable unless there’s a clear indication to transfuse. It’s also worth looking at other trials of transfusion strategies in neuro conditions. For example the TRAIN study and the SAHARA study which both showed benefit to a liberal transfusion strategy.

PREOXI – NIV vs. Standard Oxygen for Preoxygenation in Emergency Intubation

🔎 Question: Does non-invasive ventilation (NIV) improve preoxygenation before emergency intubation compared to a standard oxygen mask?

đź“Š Key Findings:

  • Lower rates of peri-intubation hypoxemia (<85% SpOâ‚‚) in the NIV group (9.1% vs. 18.5%).
  • Reduced incidence of cardiac arrest (0.2% vs. 1.1%).
  • No increase in aspiration events.

🧪 Study Strengths & Limitations:

  • Strengths: Pragmatic multicenter trial, real-world settings, high relevance.
  • Limitations: May not apply to all intubation scenarios; single-center biases possible.
  • The usual standard of care was a 15L/min face mask. This would be considered well below a standard of care in the UK. So we really don’t know whether the findings of NIV. here are better than what we do here.

đź’ˇ Bottom Line:
NIV is better than face mask oxygen at reducing hypoxia and cardiac arrest risk without increasing aspiration. However, it’s not a relevant result to my practice. Read more about the trial here on the blog.

BLING III – Continuous vs. Intermittent Beta-Lactam Infusion in Sepsis

🔎 Question: Does continuous infusion of β-lactam antibiotics improve outcomes compared to intermittent bolus dosing in septic patients?

đź“Š Key Findings:

  • No significant difference in 90-day mortality (24.9% vs. 26.8%).
  • Slightly higher clinical cure rates with continuous infusion (55.7% vs. 50.0%).

🧪 Study Strengths & Limitations:

  • Strengths: Large multicenter RCT, strong external validity.
  • Limitations: Not powered to detect small mortality differences; some subgroups may still benefit.

đź’ˇ Bottom Line:
Intermittent dosing remains a valid strategy—continuous infusion may be beneficial for select patients, but it’s not essential for all.

CLASSIC – Restrictive vs. Standard Fluids in Septic Shock

🔎 Question: Should we restrict IV fluids in ICU patients with septic shock?

đź“Š Key Findings:

  • No mortality difference at 90 days (42.3% vs. 42.1%).
  • Restrictive group received ~2L less fluid overall.
  • Similar rates of adverse events.

🧪 Study Strengths & Limitations:

  • Strengths: Large international RCT, high adherence to protocol.
  • Limitations: Conducted in centers with advanced hemodynamic monitoring, limiting generalizability.

đź’ˇ Bottom Line:
Restricting fluids doesn’t improve survival, but avoiding excessive resuscitation remains important—balance is key. This is in keeping with many other trials that ‘post-RIVERS’ have not shown a benefit to a restrictive approach (probably because the usual standard of care is to run people fairly dry most of the time).

EVIDENCE Trial – Expedited Transfer vs. On-Scene Resuscitation in Refractory OHCA.

🔎 Question: Does expedited intra-arrest transport for refractory out-of-hospital cardiac arrest (OHCA) improve survival with favorable neurological outcomes compared to extended on-scene resuscitation?

đź“Š Key Findings:

  • No significant difference in neurologically favorable survival at hospital discharge (15% expedited vs. 16% standard care).
  • No improvement in sustained circulation rates (ROSC or ECMO flow).
  • Expedited group had shorter on-scene times (26 min vs. 36 min) but longer median arrest-to-hospital times (55 min vs. 61 min).

🧪 Study Strengths & Limitations:

  • Strengths: Large, multicenter RCT, protocolized prehospital treatment approach.
  • Limitations: Limited power due to small patient numbers; ECMO availability may have influenced results.

đź’ˇ Bottom Line:
The decision to transport refractory OHCA patients should be individualized—transport alone does not improve outcomes.

VICTOR Trial – Intraosseous vs. Intravenous Access in Out-of-Hospital Cardiac Arrest

🔎 Question: Does initial vascular access via the intraosseous (IO) route improve outcomes compared to the intravenous (IV) route in adults experiencing out-of-hospital cardiac arrest?

đź“Š Key Findings:

  • Survival to hospital discharge: No significant difference between IO and IV groups.
  • Return of spontaneous circulation (ROSC): Similar rates observed in both groups.
  • Neurological outcomes: Comparable between IO and IV access methods.

🧪 Study Strengths & Limitations:

  • Strengths: Cluster randomized design, large sample size, and pragmatic approach.
  • Limitations: Conducted within a single city’s EMS system, which may limit generalizability.

đź’ˇ Bottom Line:
Initial vascular access via the IO route did not demonstrate superiority over the IV route in terms of survival or neurological outcomes in out-of-hospital cardiac arrest patients.

PARAMEDIC-3 Trial – Intraosseous vs. Intravenous Access in Out-of-Hospital Cardiac Arrest

🔎 Question: In adults with out-of-hospital cardiac arrest requiring drug therapy, does an intraosseous-first vascular access strategy improve 30-day survival compared to an intravenous-first strategy?

đź“Š Key Findings:

  • 30-day survival: No significant difference between IO-first and IV-first strategies.
  • ROSC rates: Similar between both groups.
  • Adverse events: Comparable across both access strategies.

🧪 Study Strengths & Limitations:

  • Strengths: Large multicenter randomized controlled trial across multiple EMS services.
  • Limitations: Open-label design and potential variability in paramedic proficiency with IO access.

đź’ˇ Bottom Line:
An intraosseous-first approach did not result in higher 30-day survival compared to an intravenous-first strategy in out-of-hospital cardiac arrest patients.

Final Thoughts

đźš‘ For prehospital & ED clinicians:

  • NIV is better than a face mask for preoxygenation—it reduces hypoxia and cardiac arrest risk, but we don’t know if any better than a Waters circuit (which is what we use in UK)
  • Expedited transport for refractory OHCA does not improve survival at a population basis. A bespoke approach probably better.
  • While IO access offers a rapid alternative when IV access is challenging, current evidence suggests no clear advantage of an IO-first approach over an IV-first strategy in improving survival or neurological outcomes in out-of-hospital cardiac arrest scenarios.

🏥 For ICU & sepsis care:

  • Restricting fluids alone doesn’t improve survival—tailored resuscitation is needed.
  • Intermittent β-lactam dosing remains a valid option, despite some advantages with continuous infusion.

đź’‰ For transfusion & oxygen strategies:

  • Restrictive transfusion is safe in TBI, with a potential ARDS reduction.
  • Oxygenation strategies should target SpOâ‚‚ ~94%, avoiding excessive hyperoxia.

These trials reaffirm some existing practices, challenge established assumptions, and highlight areas where more nuance is needed in decision-making.

References

  • Liberal or Restrictive Transfusion Strategy in Patients with Traumatic Brain Injury Alexis F. Turgeon, M.D. https://orcid.org/0000-0001-5675-8791, Dean A. Fergusson, Ph.D., Lucy Clayton, M.Sc., Marie-Pier Patton, M.Sc., Xavier Neveu, M.Sc., Timothy S. Walsh, M.D., AnnemarieDocherty, M.D., Ph.D., +48, for the HEMOTION Trial Investigators on behalf of the Canadian Critical Care Trials Group, the Canadian Perioperative Anesthesia Clinical Trials Group, and the Canadian Traumatic Brain Injury Research Consortium Published June 13, 2024 N Engl J Med 2024;391:722-73 DOI: 10.1056/NEJMoa2404360 VOL. 391 NO. 8
  • Gibbs KW, Semler MW, Driver BE, Seitz KP, Stempek SB, Taylor C, Resnick-Ault D, White HD, Gandotra S, Doerschug KC, Mohamed A, Prekker ME, Khan A, Gaillard JP, Andrea L, Aggarwal NR, Brainard JC, Barnett LH, Halliday SJ, Blinder V, Dagan A, Whitson MR, Schauer SG, Walker JE Jr, Barker AB, Palakshappa JA, Muhs A, Wozniak JM, Kramer PJ, Withers C, Ghamande SA, Russell DW, Schwartz A, Moskowitz A, Hansen SJ, Allada G, Goranson JK, Fein DG, Sottile PD, Kelly N, Alwood SM, Long MT, Malhotra R, Shapiro NI, Page DB, Long BJ, Thomas CB, Trent SA, Janz DR, Rice TW, Self WH, Bebarta VS, Lloyd BD, Rhoads J, Womack K, Imhoff B, Ginde AA, Casey JD; PREOXI Investigators and the Pragmatic Critical Care Research Group. Noninvasive Ventilation for Preoxygenation during Emergency Intubation. N Engl J Med. 2024 Jun 20;390(23):2165-2177. doi: 10.1056/NEJMoa2313680. Epub 2024 Jun 13. PMID: 38869091; PMCID: PMC11282951.
  • Dulhunty JM, Brett SJ, De Waele JJ, Rajbhandari D, Billot L, Cotta MO, Davis JS, Finfer S, Hammond NE, Knowles S, Liu X, McGuinness S, Mysore J, Paterson DL, Peake S, Rhodes A, Roberts JA, Roger C, Shirwadkar C, Starr T, Taylor C, Myburgh JA, Lipman J; BLING III Study Investigators. Continuous vs Intermittent β-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial. JAMA. 2024 Aug 27;332(8):629-637. doi: 10.1001/jama.2024.9779. PMID: 38864155; PMCID: PMC11170452.
  • Meyhoff TS, Hjortrup PB, Wetterslev J, Sivapalan P, Laake JH, Cronhjort M, Jakob SM, Cecconi M, Nalos M, Ostermann M, Malbrain M, Pettilä V, Møller MH, Kjær MN, Lange T, Overgaard-Steensen C, Brand BA, Winther-Olesen M, White JO, Quist L, Westergaard B, Jonsson AB, Hjortsø CJS, Meier N, Jensen TS, Engstrøm J, Nebrich L, Andersen-Ranberg NC, Jensen JV, Joseph NA, Poulsen LM, Herløv LS, Sølling CG, Pedersen SK, Knudsen KK, Straarup TS, Vang ML, Bundgaard H, Rasmussen BS, Aagaard SR, Hildebrandt T, Russell L, Bestle MH, Schønemann-Lund M, Brøchner AC, Elvander CF, Hoffmann SKL, Rasmussen ML, Martin YK, Friberg FF, Seter H, Aslam TN, Ă…dnøy S, Seidel P, Strand K, Johnstad B, Joelsson-Alm E, Christensen J, Ahlstedt C, Pfortmueller CA, Siegemund M, Greco M, RadÄ›j J, Kříž M, Gould DW, Rowan KM, Mouncey PR, Perner A; CLASSIC Trial Group. Restriction of Intravenous Fluid in ICU Patients with Septic Shock. N Engl J Med. 2022 Jun 30;386(26):2459-2470. doi: 10.1056/NEJMoa2202707. Epub 2022 Jun 17. PMID: 35709019.
  • Burns B, Marschner I, Eggins R, Buscher H, Morton RL, Bendall J, Keech A, Dennis M; EVIDENCE Investigators. A randomized trial of expedited intra-arrest transfer versus more extended on-scene resuscitation for refractory out of hospital cardiac arrest: Rationale and design of the EVIDENCE trial. Am Heart J. 2024 Jan;267:22-32. doi: 10.1016/j.ahj.2023.10.003. Epub 2023 Oct 21. PMID: 37871782.
  • Ko YC, Lin HY, Huang EP, Lee AF, Hsieh MJ, Yang CW, Lee BC, Wang YC, Yang WS, Chien YC, Sun JT, Ma MH, Chiang WC. Intraosseous versus intravenous vascular access in upper extremity among adults with out-of-hospital cardiac arrest: cluster randomised clinical trial (VICTOR trial). BMJ. 2024 Jul 23;386:e079878. doi: 10.1136/bmj-2024-079878. PMID: 39043416; PMCID: PMC11265210.
  • Couper K, Ji C, Deakin CD, Fothergill RT, Nolan JP, Long JB, Mason JM, Michelet F, Norman C, Nwankwo H, Quinn T, Slowther AM, Smyth MA, Starr KR, Walker A, Wood S, Bell S, Bradley G, Brown M, Brown S, Burrow E, Charlton K, Claxton Dip A, Dra’gon V, Evans C, Falloon J, Foster T, Kearney J, Lang N, Limmer M, Mellett-Smith A, Miller J, Mills C, Osborne R, Rees N, Spaight RES, Squires GL, Tibbetts B, Waddington M, Whitley GA, Wiles JV, Williams J, Wiltshire S, Wright A, Lall R, Perkins GD; PARAMEDIC-3 Collaborators. A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2025 Jan 23;392(4):336-348. doi: 10.1056/NEJMoa2407780. Epub 2024 Oct 31. PMID: 39480216; PMCID: PMC7616768.
  • Taccone FS, Rynkowski Bittencourt C, Møller K, Lormans P, Quintana-DĂ­az M, Caricato A, Cardoso Ferreira MA, Badenes R, Kurtz P, Søndergaard CB, Colpaert K, Petterson L, Quintard H, Cinotti R, GouvĂŞa Bogossian E, Righy C, Silva S, Roman-Pognuz E, Vandewaeter C, Lemke D, Huet O, Mahmoodpoor A, Blandino Ortiz A, van der Jagt M, Chabanne R, Videtta W, Bouzat P, Vincent JL; TRAIN Study Group. Restrictive vs Liberal Transfusion Strategy in Patients With Acute Brain Injury: The TRAIN Randomized Clinical Trial. JAMA. 2024 Nov 19;332(19):1623-1633. doi: 10.1001/jama.2024.20424. PMID: 39382241; PMCID: PMC11581574.
  • English SW, Delaney A, Fergusson DA, ChassĂ© M, Turgeon AF, Lauzier F, Tuttle A, Sadan O, Griesdale DE, Redekop G, Chapman M, Hannouche M, Kramer A, Seppelt I, Udy A, Kutsogiannis DJ, Zarychanski R, D’Aragon F, Boyd JG, Salt G, Bellapart J, Wood G, Cava L, Pickett G, Koffman L, Watpool I, Bass F, Hammond N, Ramsay T, Mallick R, Scales DC, Andersen CR, Fitzgerald E, Talbot P, Dowlatshahi D, Sinclair J, Acker J, Marshall SC, McIntyre L; SAHARA Trial Investigators on behalf of the Canadian Critical Care Trials Group. Liberal or Restrictive Transfusion Strategy in Aneurysmal Subarachnoid Hemorrhage. N Engl J Med. 2024 Dec 9. doi: 10.1056/NEJMoa2410962. Epub ahead of print. PMID: 39655786. Liberal versus Restrictive Transfusion in Aneurysmal Subarachnoid Haemorrhage. English S. NEJM 2024 DOI:10.1056/NEJMoa2410962
  • SAHARA. The Bottom Line. https://www.thebottomline.org.uk/summaries/icm/sahara-liberal-vs-restrictive-transfusion-targets-in-sah/
  • TRAIN. The Bottom Line. https://www.thebottomline.org.uk/summaries/train-transfusion-strategies-in-acute-brain-injured-patients/
  • Iain Beardsell, “Noninvasive Ventilation for Preoxygenation during Emergency Intubation,” in St.Emlyn’s, June 19, 2024, https://www.stemlynsblog.org/noninvasive-ventilation-for-preoxygenation/.

Cite this article as: Simon Carley, "More trials from TBS 2025. (part 2)," in St.Emlyn's, February 7, 2025, https://www.stemlynsblog.org/more-trials-from-tbs-2025-part-2/.

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