Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients: a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial

Chiara Robba, Rafael Badenes, Gisela Lilja, Hans Friberg, Michelle S. Chew, Johan Unden, Andreas Lundin, Martin Annborn, Josef Dankiewicz, Niklas Nielsen, Paolo Pelosi, Tobias Cronberg (Contributor), David Erlinge (Contributor), Helena Levin (Contributor), Per Nordberg (Contributor), Susann Ullén, Karolina Palmér (Contributor), Ulla Britt Karlsson (Contributor), Simon Heissler (Contributor), Ameldina Ceric (Contributor)Zana Haxhija (Contributor), Joachim Düring (Contributor), Mattias Bergström (Contributor), Ingrid Didriksson (Contributor), Petrea Frid (Contributor), Katarina Heimburg (Contributor), Oscar Lundberg (Contributor), Stefan Olsson Hau (Contributor), Simon Schmidbauer (Contributor), Ola Borgquist (Contributor), Anna Bjärnroos (Contributor), Erik Blennow Nordström (Contributor), Irina Dragancea (Contributor), Thomas Kander (Contributor), Anna Lybeck (Contributor), Gustav Mattiasson (Contributor), Olof Persson (Contributor), Malin Rundgren (Contributor), Erik Westhall (Contributor), Sara Andertun (Contributor), Florian Ebner (Contributor), Jesper Johnsson (Contributor), on behalf of the TTM2 Trial Collaborators

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Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.

Original languageEnglish
Pages (from-to)1024-1038
Number of pages15
JournalIntensive Care Medicine
Issue number8
Publication statusPublished - 2022 Aug

Bibliographical note

Funding Information:
MS, receiving consulting fees from Bard Medical; PJY, receiving lecture fees from Bard Medical; FST, receiving grant support from Bard Medical and ZOLL Medical; AN, receiving grant support, paid to University College Dublin, from AM Pharma and grant sup-port, paid to Monash University, from Baxter Healthcare; MSC, receiving lecture fees from Edwards Lifesciences; HF, receiving fees for academic advising from TEQCool; and NN, receiving lecture fees from Bard Medical and consulting fees from BrainCool. RB is supported by INCLIVA. No other potential conflict of interest relevant to this article was reported.

Funding Information:
Open access funding provided by Università degli Studi di Genova within the CRUI-CARE Agreement. The TTM2 trial was supported by independent research grants from nonprofit or governmental agencies (the Swedish Research Council [Veten-skapsrådet], Swedish Heart–Lung Foundation, Stig and Ragna Gorthon Foundation, Knutsson Foundation, Laerdal Foundation, Hans-Gabriel and Alice Trolle-Wachtmeister Foundation for Medical Research, and Regional Research Support in Region Skåne) and by governmental funding of clinical research within the Swedish National Health Service. No further fundings were requested for this subanalysis.

Publisher Copyright:
© 2022, The Author(s).

Subject classification (UKÄ)

  • Cardiac and Cardiovascular Systems
  • Anesthesiology and Intensive Care

Free keywords

  • Cardiac arrest
  • Driving pressure
  • Mechanical power
  • Mechanical ventilation
  • Outcome
  • Ventilator settings


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