Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest: A secondary analysis of the TTM-2 trial

Filippo Sanfilippo; Agnieszka Uryga; Cristina Santonocito; Janus Christian Jakobsen; Gisela Lilja; Hans Friberg; Pedro David Wendel-Garcia; Paul J Young; Glenn Eastwood; Michelle S Chew; Johan Unden; Matthew Thomas; Anders M Grejs; Matt P Wise; Andreas Lundin; Jacob Hollenberg; Naomi Hammond; Manoj Saxena; Annborn Martin; Robert Bánszky; Fabio Silvio Taccone; Josef Dankiewicz; Niklas Nielsen; Florian Ebner; Jan BeloholaveK; Matthias Hanggi; Luca Montagnani; Nicolo' Patroniti; Chiara Robba; TTM-2 investigators

doi:10.1016/j.resuscitation.2024.110460

Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest: A secondary analysis of the TTM-2 trial

Filippo Sanfilippo
, Agnieszka Uryga
, Cristina Santonocito
, Janus Christian Jakobsen
, Gisela Lilja
, Hans Friberg
, Pedro David Wendel-Garcia
, Paul J Young
, Glenn Eastwood
, Michelle S Chew
, Johan Unden
, Matthew Thomas
, Anders M Grejs
, Matt P Wise
, Andreas Lundin
, Jacob Hollenberg
, Naomi Hammond
, Manoj Saxena
, Annborn Martin
, Robert Bánszky

Fabio Silvio Taccone, Josef Dankiewicz, Niklas Nielsen, Florian Ebner, Jan BeloholaveK, Matthias Hanggi, Luca Montagnani, Nicolo' Patroniti, Chiara Robba^*, TTM-2 investigators

^*Corresponding author for this work

Copenhagen Trial Unit

11 Citations (Scopus)

Abstract

PURPOSE: Hyperoxemia is common in patients resuscitated after out-of-hospital cardiac arrest (OHCA) admitted to the intensive care unit (ICU) and may increase the risk of mortality. However, the effect of hyperoxemia on functional outcome, specifically related to the timing of exposure to hyperoxemia, remains unclear.

METHODS: The secondary analysis of the Target Temperature Management 2 (TTM-2) randomized trial. The primary aim was to identify the best cut-off of partial arterial pressure of oxygen (PaO2) to predict poor functional outcome within the first 24 h from admission, with this period further separated into 'very early' (0-4 h), 'early' (8-24 h), and 'late' (28-72 h) periods. Hyperoxemia was defined as the highest PaO2 recorded during each period. Poor functional outcome was defined as a 6 months modified Rankin Score (mRS) of 4 to 6.

RESULTS: A total of 1,631 patients were analysed for the 'very early' and 'early' periods, and 1,591 in the 'late period'. In a multivariate logistic regression model, a PaO2 above 245 mmHg during the very early phase was independently associated with a higher probability of poor functional outcome (Odds Ratio, OR = 1.63, 95 % Confidence Interval, CI 1.08-2.44, p = 0.019). No significant associations were found for the later periods.

CONCLUSIONS: Very early hyperoxemia after ICU admission is associated with higher risk of poor functional outcome after OHCA. Avoiding hyperoxia in the initial hours after resuscitation should be considered.

Original language	English
Article number	110460
Journal	Resuscitation
Volume	207
ISSN	0300-9572
DOIs	https://doi.org/10.1016/j.resuscitation.2024.110460
Publication status	Published - 2025

Keywords

Cardiac arrest
Functional outcome
Oxygen radicals
Oxygenation
Timing

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10.1016/j.resuscitation.2024.110460

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Sanfilippo, F., Uryga, A., Santonocito, C., Jakobsen, J. C., Lilja, G., Friberg, H., Wendel-Garcia, P. D., Young, P. J., Eastwood, G., Chew, M. S., Unden, J., Thomas, M., Grejs, A. M., Wise, M. P., Lundin, A., Hollenberg, J., Hammond, N., Saxena, M., Martin, A., ... TTM-2 investigators (2025). Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest: A secondary analysis of the TTM-2 trial. Resuscitation, 207, Article 110460. https://doi.org/10.1016/j.resuscitation.2024.110460

Sanfilippo, F, Uryga, A, Santonocito, C, Jakobsen, JC, Lilja, G, Friberg, H, Wendel-Garcia, PD, Young, PJ, Eastwood, G, Chew, MS, Unden, J, Thomas, M, Grejs, AM, Wise, MP, Lundin, A, Hollenberg, J, Hammond, N, Saxena, M, Martin, A, Bánszky, R, Taccone, FS, Dankiewicz, J, Nielsen, N, Ebner, F, BeloholaveK, J, Hanggi, M, Montagnani, L, Patroniti, N, Robba, C & TTM-2 investigators 2025, 'Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest: A secondary analysis of the TTM-2 trial', Resuscitation, vol. 207, 110460. https://doi.org/10.1016/j.resuscitation.2024.110460

@article{8a5e6e880a754d4cb4acdc5559103920,

title = "Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest: A secondary analysis of the TTM-2 trial",

abstract = "PURPOSE: Hyperoxemia is common in patients resuscitated after out-of-hospital cardiac arrest (OHCA) admitted to the intensive care unit (ICU) and may increase the risk of mortality. However, the effect of hyperoxemia on functional outcome, specifically related to the timing of exposure to hyperoxemia, remains unclear.METHODS: The secondary analysis of the Target Temperature Management 2 (TTM-2) randomized trial. The primary aim was to identify the best cut-off of partial arterial pressure of oxygen (PaO2) to predict poor functional outcome within the first 24 h from admission, with this period further separated into 'very early' (0-4 h), 'early' (8-24 h), and 'late' (28-72 h) periods. Hyperoxemia was defined as the highest PaO2 recorded during each period. Poor functional outcome was defined as a 6 months modified Rankin Score (mRS) of 4 to 6.RESULTS: A total of 1,631 patients were analysed for the 'very early' and 'early' periods, and 1,591 in the 'late period'. In a multivariate logistic regression model, a PaO2 above 245 mmHg during the very early phase was independently associated with a higher probability of poor functional outcome (Odds Ratio, OR = 1.63, 95 \% Confidence Interval, CI 1.08-2.44, p = 0.019). No significant associations were found for the later periods.CONCLUSIONS: Very early hyperoxemia after ICU admission is associated with higher risk of poor functional outcome after OHCA. Avoiding hyperoxia in the initial hours after resuscitation should be considered.",

keywords = "Cardiac arrest, Functional outcome, Oxygen radicals, Oxygenation, Timing",

author = "Filippo Sanfilippo and Agnieszka Uryga and Cristina Santonocito and Jakobsen, \{Janus Christian\} and Gisela Lilja and Hans Friberg and Wendel-Garcia, \{Pedro David\} and Young, \{Paul J\} and Glenn Eastwood and Chew, \{Michelle S\} and Johan Unden and Matthew Thomas and Grejs, \{Anders M\} and Wise, \{Matt P\} and Andreas Lundin and Jacob Hollenberg and Naomi Hammond and Manoj Saxena and Annborn Martin and Robert B{\'a}nszky and Taccone, \{Fabio Silvio\} and Josef Dankiewicz and Niklas Nielsen and Florian Ebner and Jan BeloholaveK and Matthias Hanggi and Luca Montagnani and Nicolo' Patroniti and Chiara Robba and \{TTM-2 investigators\}",

note = "Copyright {\textcopyright} 2024. Published by Elsevier B.V.",

year = "2025",

doi = "10.1016/j.resuscitation.2024.110460",

language = "English",

volume = "207",

journal = "Resuscitation",

issn = "0300-9572",

publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest

T2 - A secondary analysis of the TTM-2 trial

AU - Sanfilippo, Filippo

AU - Uryga, Agnieszka

AU - Santonocito, Cristina

AU - Jakobsen, Janus Christian

AU - Lilja, Gisela

AU - Friberg, Hans

AU - Wendel-Garcia, Pedro David

AU - Young, Paul J

AU - Eastwood, Glenn

AU - Chew, Michelle S

AU - Unden, Johan

AU - Thomas, Matthew

AU - Grejs, Anders M

AU - Wise, Matt P

AU - Lundin, Andreas

AU - Hollenberg, Jacob

AU - Hammond, Naomi

AU - Saxena, Manoj

AU - Martin, Annborn

AU - Bánszky, Robert

AU - Taccone, Fabio Silvio

AU - Dankiewicz, Josef

AU - Nielsen, Niklas

AU - Ebner, Florian

AU - BeloholaveK, Jan

AU - Hanggi, Matthias

AU - Montagnani, Luca

AU - Patroniti, Nicolo'

AU - Robba, Chiara

AU - TTM-2 investigators

PY - 2025

Y1 - 2025

N2 - PURPOSE: Hyperoxemia is common in patients resuscitated after out-of-hospital cardiac arrest (OHCA) admitted to the intensive care unit (ICU) and may increase the risk of mortality. However, the effect of hyperoxemia on functional outcome, specifically related to the timing of exposure to hyperoxemia, remains unclear.METHODS: The secondary analysis of the Target Temperature Management 2 (TTM-2) randomized trial. The primary aim was to identify the best cut-off of partial arterial pressure of oxygen (PaO2) to predict poor functional outcome within the first 24 h from admission, with this period further separated into 'very early' (0-4 h), 'early' (8-24 h), and 'late' (28-72 h) periods. Hyperoxemia was defined as the highest PaO2 recorded during each period. Poor functional outcome was defined as a 6 months modified Rankin Score (mRS) of 4 to 6.RESULTS: A total of 1,631 patients were analysed for the 'very early' and 'early' periods, and 1,591 in the 'late period'. In a multivariate logistic regression model, a PaO2 above 245 mmHg during the very early phase was independently associated with a higher probability of poor functional outcome (Odds Ratio, OR = 1.63, 95 % Confidence Interval, CI 1.08-2.44, p = 0.019). No significant associations were found for the later periods.CONCLUSIONS: Very early hyperoxemia after ICU admission is associated with higher risk of poor functional outcome after OHCA. Avoiding hyperoxia in the initial hours after resuscitation should be considered.

AB - PURPOSE: Hyperoxemia is common in patients resuscitated after out-of-hospital cardiac arrest (OHCA) admitted to the intensive care unit (ICU) and may increase the risk of mortality. However, the effect of hyperoxemia on functional outcome, specifically related to the timing of exposure to hyperoxemia, remains unclear.METHODS: The secondary analysis of the Target Temperature Management 2 (TTM-2) randomized trial. The primary aim was to identify the best cut-off of partial arterial pressure of oxygen (PaO2) to predict poor functional outcome within the first 24 h from admission, with this period further separated into 'very early' (0-4 h), 'early' (8-24 h), and 'late' (28-72 h) periods. Hyperoxemia was defined as the highest PaO2 recorded during each period. Poor functional outcome was defined as a 6 months modified Rankin Score (mRS) of 4 to 6.RESULTS: A total of 1,631 patients were analysed for the 'very early' and 'early' periods, and 1,591 in the 'late period'. In a multivariate logistic regression model, a PaO2 above 245 mmHg during the very early phase was independently associated with a higher probability of poor functional outcome (Odds Ratio, OR = 1.63, 95 % Confidence Interval, CI 1.08-2.44, p = 0.019). No significant associations were found for the later periods.CONCLUSIONS: Very early hyperoxemia after ICU admission is associated with higher risk of poor functional outcome after OHCA. Avoiding hyperoxia in the initial hours after resuscitation should be considered.

KW - Cardiac arrest

KW - Functional outcome

KW - Oxygen radicals

KW - Oxygenation

KW - Timing

UR - https://www.scopus.com/pages/publications/85212338674

U2 - 10.1016/j.resuscitation.2024.110460

DO - 10.1016/j.resuscitation.2024.110460

M3 - Journal article

C2 - 39653237

SN - 0300-9572

VL - 207

JO - Resuscitation

JF - Resuscitation

M1 - 110460

ER -

Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest: A secondary analysis of the TTM-2 trial

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