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. 2022 Aug;48(8):1024-1038.
doi: 10.1007/s00134-022-06756-4. Epub 2022 Jul 2.

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  1   2 , Rafael Badenes  3   4 , Denise Battaglini  5   6 , Lorenzo Ball  5   7 , Iole Brunetti  5 , Janus C Jakobsen  8   9 , Gisela Lilja  10 , Hans Friberg  11 , Pedro D Wendel-Garcia  12 , Paul J Young  13   14   15   16 , Glenn Eastwood  17 , Michelle S Chew  18 , Johan Unden  19   20 , Matthew Thomas  21 , Michael Joannidis  22 , Alistair Nichol  23 , Andreas Lundin  24 , Jacob Hollenberg  25 , Naomi Hammond  26 , Manoj Saxena  27 , Martin Annborn  28 , Miroslav Solar  29   30 , Fabio S Taccone  31 , Josef Dankiewicz  32 , Niklas Nielsen #  33 , Paolo Pelosi #  5   7 ; TTM2 Trial Collaborators
Collaborators, Affiliations

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 et al. Intensive Care Med. 2022 Aug.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT02908308.

Keywords: Cardiac arrest; Driving pressure; Mechanical power; Mechanical ventilation; Outcome; Ventilator settings.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Hourly trajectories of different ventilator settings/parameters according to survival status. Predicted values from a mixed regression analysis with random intercept. PEEP positive end-expiratory pressure; PBW predicted body weight; FiO2 fraction of inspired oxygen
Fig. 2
Fig. 2
Relative distribution analysis for the definition of the best cut-off associated with mortality for each parameter. Best cut-off point along the continuum of the marker that separated survivors versus non survivors at the end of the follow-up. In this analysis, the quantile (or proportion) distribution of the marker survivors (plotted on the x-axis plus the corresponding marker values at the top) is plotted against the proportion ratio of the marker distribution for non survivors. PEEP positive end-expiratory pressure; PBW predicted body weight; FiO2
Fig. 3
Fig. 3
a, b Ventilatory markers and 6-month mortality. This regression model was adjusted by (1) clinical variables: TTM2 randomization group, age (years), Charlson comorbidity index, cardiac arrest witnessed, ROSC (min), bystander performed CPR, shockable rhythm, cardiac arrest location (home, public place, other), shock diagnosis on admission, and STEMI diagnosis on admission; (2) arterial blood gas values: arterial partial pressure of oxygen (PaO2) (mmHg)/Fraction of inspired oxygen (FiO2) ratio, arterial partial pressure of carbon dioxide (PaCO2) (mmHg), pH, and Base excess (mEq/L); and (3) by the above markers among them. PEEP, positive end-expiratory pressure.
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