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, Denise Battaglini, Lorenzo Ball, Iole Brunetti, Janus C Jakobsen, Gisela Lilja, Hans Friberg, Pedro D Wendel-Garcia, Paul J Young, Glenn Eastwood, Michelle S Chew, Johan Unden, Matthew Thomas, Michael Joannidis, Alistair Nichol, Andreas Lundin, Jacob Hollenberg, Naomi Hammond, Manoj Saxena, Martin Annborn, Miroslav Solar, Fabio S Taccone, Josef Dankiewicz, Niklas Nielsen, Paolo Pelosi, TTM2 Trial Collaborators

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.

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.

© 2022. The Author(s).

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.

References

    1. Kim Y-M, Yim H-W, Jeong S-H, Klem ML, Callaway CW. Does therapeutic hypothermia benefit adult cardiac arrest patients presenting with non-shockable initial rhythms? A systematic review and meta-analysis of randomized and non-randomized studies. Resuscitation. 2012;83:188–196.
    1. Robba C, Siwicka-Gieroba D, Sikter A, Battaglini D, Dąbrowski W, Schultz MJ, et al. Pathophysiology and clinical consequences of arterial blood gases and pH after cardiac arrest. Intensive Care Med Exp. 2020;8:19.
    1. Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016;315:788.
    1. Neto AS, Barbas CSV, Simonis FD, Artigas-Raventós A, Canet J, Determann RM, et al. Epidemiological characteristics, practice of ventilation, and clinical outcome in patients at risk of acute respiratory distress syndrome in intensive care units from 16 countries (PRoVENT): an international, multicentre, prospective study. Lancet Respir Med. 2016;4:882–893.
    1. Sutherasan Y, Peñuelas O, Muriel A, Vargas M, Frutos-Vivar F, Brunetti I, et al. Management and outcome of mechanically ventilated patients after cardiac arrest. Crit Care. 2015;19:215.
    1. Harmon MBA, van Meenen DMP, van der Veen ALIP, Binnekade JM, Dankiewicz J, Ebner F, et al. Practice of mechanical ventilation in cardiac arrest patients and effects of targeted temperature management: a substudy of the targeted temperature management trial. Resuscitation. 2018;129:29–36.
    1. EL Costa V, Slutsky AS, Brochard LJ, Brower R, Serpa-Neto A, Cavalcanti AB, et al. Ventilatory variables and mechanical power in patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 2021;204:303–311.
    1. Robba C, Nielsen N, Dankiewicz J, Badenes R, Battaglini D, Ball L, et al. Ventilation management and outcomes in out-of-hospital cardiac arrest: a protocol for a preplanned secondary analysis of the TTM2 trial. BMJ Open. 2022;12:e058001.
    1. Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Bělohlávek J, Callaway C, et al. Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): a randomized clinical trial—rationale and design. Am Heart J. 2019;217:23–31.
    1. Dankiewicz J, Cronberg T, Lilja G, Jakobsen JC, Levin H, Ullén S, et al. Hypothermia versus normothermia after out-of-hospital cardiac arrest. N Engl J Med. 2021;384:2283–2294.
    1. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370:1453–1457.
    1. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47:1245–1251.
    1. Gattinoni L, Tonetti T, Cressoni M, Cadringher P, Herrmann P, Moerer O, et al. Ventilator-related causes of lung injury: the mechanical power. Intensive Care Med. 2016;42:1567–1575.
    1. Sinha P, Calfee CS, Beitler JR, Soni N, Ho K, Matthay MA, et al. Physiologic analysis and clinical performance of the ventilatory ratio in acute respiratory distress syndrome. Am J Respir Crit Care Med. 2019;199:333–341.
    1. Royston P, Saurbrei W (2008) Multivariable model-building: a pragmatic approach to regression anaylsis based on fractional polynomials for modelling continuous variables.
    1. Jann B. Relative distribution analysis in Stata. Stata J [Internet] 2020;21:885–951.
    1. Young PJ, Bailey M, Bellomo R, Bernard S, Bray J, Jakkula P, et al. Conservative or liberal oxygen therapy in adults after cardiac arrest. Resuscitation. 2020;157:15–22.
    1. Roberts BW, Kilgannon JH, Chansky ME, Mittal N, Wooden J, Trzeciak S. Association between postresuscitation partial pressure of arterial carbon dioxide and neurological outcome in patients with post–cardiac arrest syndrome. Circulation. 2013;127:2107–2113.
    1. Palmer E, Post B, Klapaukh R, Marra G, MacCallum NS, Brealey D, et al. The association between supraphysiologic arterial oxygen levels and mortality in critically ill patients. A multicenter observational cohort study. Am J Respir Crit Care Med. 2019;200:1373–1380.
    1. Pilcher J, Weatherall M, Shirtcliffe P, Bellomo R, Young P, Beasley R. The effect of hyperoxia following cardiac arrest: a systematic review and meta-analysis of animal trials. Resuscitation. 2012;83:417–422.
    1. Roberts BW, Kilgannon J, Chansky ME, Trzeciak S. Association between initial prescribed minute ventilation and post-resuscitation partial pressure of arterial carbon dioxide in patients with post-cardiac arrest syndrome. Ann Intensive Care. 2014;4:9.
    1. Tejerina E, Pelosi P, Muriel A, Peñuelas O, Sutherasan Y, Frutos-Vivar F, et al. Association between ventilatory settings and development of acute respiratory distress syndrome in mechanically ventilated patients due to brain injury. J Crit Care. 2017;38:341–345.
    1. Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: post-resuscitation care. Intensive Care Med. 2021;47:369–421.
    1. Lundbye JB, Rai M, Ramu B, Hosseini-Khalili A, Li D, Slim HB, et al. Therapeutic hypothermia is associated with improved neurologic outcome and survival in cardiac arrest survivors of non-shockable rhythms. Resuscitation. 2012;83:202–207.
    1. Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European Resuscitation Council and European Society of Intensive Care Medicine Guidelines 2021: post-resuscitation care. Resuscitation. 2021;161:220–269.
    1. Serpa Neto A, Deliberato RO, Johnson AEW, Bos LD, Amorim P, Pereira SM, et al. Mechanical power of ventilation is associated with mortality in critically ill patients: an analysis of patients in two observational cohorts. Intensive Care Med. 2018;44:1914–1922.
    1. Coppola S, Caccioppola A, Froio S, Formenti P, De Giorgis V, Galanti V, et al. Effect of mechanical power on intensive care mortality in ARDS patients. Crit Care. 2020;24:246.
    1. Bellani G, Grassi A, Sosio S, Gatti S, Kavanagh BP, Pesenti A, et al. Driving pressure is associated with outcome during assisted ventilation in acute respiratory distress syndrome. Anesthesiology. 2019;131:594–604.
    1. Toufen Junior C, De Santis Santiago RR, Hirota AS, Carvalho ARS, Gomes S, Amato MBP, et al. Driving pressure and long-term outcomes in moderate/severe acute respiratory distress syndrome. Ann Intensive Care. 2018;8:119.
    1. Guo L, Xie J, Huang Y, Pan C, Yang Y, Qiu H, et al. Higher PEEP improves outcomes in ARDS patients with clinically objective positive oxygenation response to PEEP: a systematic review and meta-analysis. BMC Anesthesiol. 2018;18:172.
    1. Serpa Neto A, Filho RR, Cherpanath T, Determann R, Dongelmans DA, Paulus F, et al. Associations between positive end-expiratory pressure and outcome of patients without ARDS at onset of ventilation: a systematic review and meta-analysis of randomized controlled trials. Ann Intensive Care. 2016;6:109.
    1. Torres A, Motos A, Riera J, Fernández-Barat L, Ceccato A, Pérez-Arnal R, et al. The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients. Crit Care. 2021;25:331.
    1. Amato MBP, Barbas CSV, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998;338:347–354.
    1. Brower R, Matthay M, Morris A, Schoenfeld D, Thompson B, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000;342:1301–1308.
    1. Simonis FD, Serpa Neto A, Binnekade JM, Braber A, Bruin KCM, Determann RM, et al. Effect of a low vs intermediate tidal volume strategy on ventilator-free days in intensive care unit patients without ARDS. JAMA. 2018;320:1872.
    1. Tiruvoipati R, Pilcher D, Botha J, Buscher H, Simister R, Bailey M. Association of hypercapnia and hypercapnic acidosis with clinical outcomes in mechanically ventilated patients with cerebral injury. JAMA Neurol. 2018;75:818–826.
    1. Beitler JR, Ghafouri TB, Jinadasa SP, Mueller A, Hsu L, Anderson RJ, et al. Favorable neurocognitive outcome with low tidal volume ventilation after cardiac arrest. Am J Respir Crit Care Med. 2017;195:1198–1206.
    1. Eastwood GM, Nichol A. Optimal ventilator settings after return of spontaneous circulation. Curr Opin Crit Care. 2020;26:251–258.
    1. Eastwood GM, Young PJ, Bellomo R. The impact of oxygen and carbon dioxide management on outcome after cardiac arrest. Curr Opin Crit Care. 2014;20:266–272.
    1. Farias LL, Faffe DS, Xisto DG, Santana MCE, Lassance R, Prota LFM, et al. Positive end-expiratory pressure prevents lung mechanical stress caused by recruitment/derecruitment. J Appl Physiol. 2005;98:53–61.
    1. Ricard J-D, Dreyfuss D, Saumon G. Ventilator-induced lung injury. Eur Respir J. 2003;22:2s–9s.
    1. Schaefer MS, Serpa Neto A, Pelosi P, de Gama AM, Kienbaum P, Schultz MJ, et al. Temporal changes in ventilator settings in patients with uninjured lungs. Anesth Analg. 2019;129:129–140.
    1. Tejerina EE, Pelosi P, Robba C, Peñuelas O, Muriel A, Barrios D, et al. Evolution over time of ventilatory management and outcome of patients with neurologic disease. Crit Care Med. 2021;49:1095–1106.
    1. Esteban A. Characteristics and outcomes in adult patients receiving mechanical ventilation: a 28-day international study. JAMA. 2002;287:345.
    1. Sahetya SK, Fan E. Driving pressure: the road ahead. Respir Care. 2019;64:1017–1020.
    1. Cressoni M, Gotti M, Chiurazzi C, Massari D, Algieri I, Amini M, et al. Mechanical power and development of ventilator-induced lung injury. Anesthesiology. 2016;124:1100–1108.
    1. Scharffenberg M, Wittenstein J, Ran X, Zhang Y, Braune A, Theilen R, et al. Mechanical power correlates with lung inflammation assessed by positron-emission tomography in experimental acute lung injury in pigs. Front Physiol. 2021;12:717266.
    1. Malik AB, Krasney JA, Royce GJ. Respiratory influence on the total and regional cerebral blood flow responses to intracranial hypertension. Stroke. 1977;8:243–249.
    1. Heffner JE. Controlled hyperventilation in patients with intracranial hypertension. Arch Intern Med. 1983;143:765.
    1. Nuckton TJ, Alonso JA, Kallet RH, Daniel BM, Pittet J-F, Eisner MD, et al. Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome. N Engl J Med. 2002;346:1281–1286.
    1. Goligher EC, EL Costa V, Yarnell CJ, Brochard LJ, Stewart TE, Tomlinson G, et al. Effect of lowering Vt on mortality in acute respiratory distress syndrome varies with respiratory system elastance. Am J Respir Crit Care Med. 2021;203:1378–1385.

Source: PubMed

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