Randomized Controlled Trial

. 2019 Jan 28;23(1):30.

doi: 10.1186/s13054-019-2322-z.

Associations between partial pressure of oxygen and neurological outcome in out-of-hospital cardiac arrest patients: an explorative analysis of a randomized trial

Florian Ebner¹, Susann Ullén², Anders Åneman³, Tobias Cronberg⁴, Niklas Mattsson⁴, Hans Friberg⁵, Christian Hassager^{6

7}, Jesper Kjærgaard^{6

7}, Michael Kuiper⁸, Paolo Pelosi^{9

10}, Johan Undén¹¹, Matt P Wise¹², Jørn Wetterslev¹³, Niklas Nielsen¹⁴

Affiliations

¹ Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, S-251 87, Helsingborg, Sweden. florian.ebner@med.lu.se.
² Clinical Studies Sweden, Skane University Hospital, Remissgatan 4, S-221 85, Lund, Sweden.
³ Department of Intensive Care, Liverpool Hospital, Locked Bag 7103, Liverpool BC, Sydney, NSW, 1871, Australia.
⁴ Department of Clinical Sciences Lund, Neurology, Lund University, Skane University Hospital, Getingevägen 5, 221 85, Lund, Sweden.
⁵ Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Skane University Hospital, Getingevägen 5, 221 85, Lund, Sweden.
⁶ Department of Cardiology, Rigshospitalet, University of Copenhagen, DK 2100, Copenhagen, Denmark.
⁷ Department of Clinical Medicine, University of Copenhagen, DK 2100, Copenhagen, Denmark.
⁸ Intensive Care Unit, Leeuwarden Medical Centrum, Borniastraat 38, NL8934 AD, Leeuwarden, Netherlands.
⁹ Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.
¹⁰ Department of Anesthesia and Intensive Care, IRCCS San Martino Policlinico Hospital, Genoa, Italy.
¹¹ Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Hallands Hospital, S-30233, Halmstad, Sweden.
¹² Adult Critical Care, University Hospital of Wales, Heath Park, Cardiff, CF144XW, UK.
¹³ Copenhagen Trial Unit, Centre for Clinical Intervention Research, Dpt. 7812, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
¹⁴ Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, S-251 87, Helsingborg, Sweden.

PMID: 30691510
PMCID: PMC6348606
DOI: 10.1186/s13054-019-2322-z

Randomized Controlled Trial

Associations between partial pressure of oxygen and neurological outcome in out-of-hospital cardiac arrest patients: an explorative analysis of a randomized trial

Florian Ebner et al. Crit Care. 2019.

. 2019 Jan 28;23(1):30.

doi: 10.1186/s13054-019-2322-z.

Authors

Affiliations

¹ Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, S-251 87, Helsingborg, Sweden. florian.ebner@med.lu.se.
² Clinical Studies Sweden, Skane University Hospital, Remissgatan 4, S-221 85, Lund, Sweden.
³ Department of Intensive Care, Liverpool Hospital, Locked Bag 7103, Liverpool BC, Sydney, NSW, 1871, Australia.
⁴ Department of Clinical Sciences Lund, Neurology, Lund University, Skane University Hospital, Getingevägen 5, 221 85, Lund, Sweden.
⁵ Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Skane University Hospital, Getingevägen 5, 221 85, Lund, Sweden.
⁶ Department of Cardiology, Rigshospitalet, University of Copenhagen, DK 2100, Copenhagen, Denmark.
⁷ Department of Clinical Medicine, University of Copenhagen, DK 2100, Copenhagen, Denmark.
⁸ Intensive Care Unit, Leeuwarden Medical Centrum, Borniastraat 38, NL8934 AD, Leeuwarden, Netherlands.
⁹ Department of Surgical Sciences and Integrated Diagnostics, University of Genoa, Genoa, Italy.
¹⁰ Department of Anesthesia and Intensive Care, IRCCS San Martino Policlinico Hospital, Genoa, Italy.
¹¹ Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Hallands Hospital, S-30233, Halmstad, Sweden.
¹² Adult Critical Care, University Hospital of Wales, Heath Park, Cardiff, CF144XW, UK.
¹³ Copenhagen Trial Unit, Centre for Clinical Intervention Research, Dpt. 7812, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
¹⁴ Department of Clinical Sciences Lund, Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, S-251 87, Helsingborg, Sweden.

PMID: 30691510
PMCID: PMC6348606
DOI: 10.1186/s13054-019-2322-z

Abstract

Objective: Exposure to hyperoxemia and hypoxemia is common in out-of-hospital cardiac arrest (OHCA) patients following return of spontaneous circulation (ROSC), but its effects on neurological outcome are uncertain, and study results are inconsistent.

Methods: Exploratory post hoc substudy of the Target Temperature Management (TTM) trial, including 939 patients after OHCA with return of spontaneous circulation (ROSC). The association between serial arterial partial pressures of oxygen (PaO₂) during 37 h following ROSC and neurological outcome at 6 months, evaluated by Cerebral Performance Category (CPC), dichotomized to good (CPC 1-2) and poor (CPC 3-5), was investigated. In our analyses, we tested the association of hyperoxemia and hypoxemia, time-weighted mean PaO₂, maximum PaO₂ difference, and gradually increasing PaO₂ levels (13.3-53.3 kPa) with poor neurological outcome. A subsequent analysis investigated the association between PaO₂ and a biomarker of brain injury, peak serum Tau levels.

Results: Eight hundred sixty-nine patients were eligible for analysis. Three hundred patients (35%) were exposed to hyperoxemia or hypoxemia at some time point after ROSC. Our analyses did not reveal a significant association between hyperoxemia, hypoxemia, time-weighted mean PaO₂ exposure or maximum PaO₂ difference and poor neurological outcome at 6-month follow-up after correction for co-variates (all analyses p = 0.146-0.847). We were not able to define a PaO₂ level significantly associated with the onset of poor neurological outcome. Peak serum Tau levels at either 48 or 72 h after ROSC were not associated with PaO₂.

Conclusion: Hyperoxemia or hypoxemia exposure occurred in one third of the patients during the first 37 h of hospitalization and was not significantly associated with poor neurological outcome after 6 months or with the peak s-Tau levels at either 48 or 72 h after ROSC.

Keywords: Biomarker; Cerebral performance; Out of hospital cardiac arrest; Partial pressure of oxygen; Serum tau.

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Conflict of interest statement

Ethics approval and consent to participate

The TTM trial protocol was approved by ethics committees in the following institutions: St George Hospital, Sydney. North Shore Hospital, Sydney. Liverpool Hospital, Sydney. The George Institute of Global Health, Sydney. General University Hospital in Prague, Prague. The Heart Center, Copenhagen University Hospital Rigshospitalet, Copenhagen. Ospedale Universitario di Cattinara, Trieste. Santa Maria degli Angeli Hospital, Pordenone. San Martino, Genoa. Medical Centre, Luxembourg. Amsterdam Medical Centre, Amsterdam. Leeuwarden Hospital, Leeuwarden. Rijnstaate Hospital, Arnhem. Onze Lieuwe Vrouwe Gasthuis, Amsterdam. Oslo University Hospital, Oslo. Haukeland University Hospital, Bergen. Helsingborg Hospital, Helsingborg. Karlstad Hospital, Karlstad. Kungälv Hospital, Kungälv: Linköping University Hospital, Linköping. Skåne University Hospital, Lund. Skåne University Hospital, Malmö. Norra Älvsborgs Län Hospital. Vrinnevi Hospital, Norrköping.

Sahlgrenska University Hospital, Gothenburg. Örebro University Hospital, Örebro. Geneva University Hospital, Geneva. Hospital St Gallen, St Gallen. Hospital La Chaux de Fonds. University Hospital of Wales, Cardiff. Royal Berkshire Hospital, Reading. Royal Bournemouth Hospital, Bournemouth. Guy’s and St Thomas’ NHS Trust, London. St George’s Hospital, London. Informed consent was waived or was obtained according to national legislation, in line with the Helsinki declaration.

Consent for publication

Not applicable.

Competing interests

H.F. has received lecture fees from Bard Medical and is scientific advisor at QuickCool.

M.P.W. has done an advisory board and educational meeting for Bard Medical, N.N. has received lecture fees from Bard Medical. The remaining authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
Patient selection pathway. TTM, targeted temperature management. TTM group, 33 or 36 °C core body temperature derived from the TTM trial [24]. n, number of patients. The diagram does not display the selection pathway for the s-Tau analysis

**Fig. 2**
Boxplots depicting the distributional characteristics of PaO₂ at 8 measurement points from admission to hospital to the end of intervention time for the TTM 33 and TTM 36 groups (a) and the investigated combined cohort dichotomized into good and poor outcome (b). Boxplot values are displayed as median, 25% quartiles from median and range. TTM, target temperature management. PaO₂, partial arterial oxygen pressure. kPa, kilopascal. Core body temperature, 33 °C or 36 °C. White circle denotes the outliers. Asterisk denotes extreme outliers

**Fig. 3**
Forrest plot showing the adjusted OR’s (bullet points) with 95% CI’s (horizontal lines) for poor neurological outcome according to Cerebral Performance Category (CPC) for different PaO₂ threshold values. OR, odds ratio. CI, confidence interval. PaO_2, partial pressure of oxygen. kPa, kilopascal. CPC, cerebral performance category. CPC 1-2, good outcome, CPC 3-5, poor outcome. ORs and CIs are presented on a logarithmic scale. OR above 1.0 indicates worse outcome above the PaO₂ threshold and OR below 1.0 indicates better outcome above the PaO₂ threshold

See this image and copyright information in PMC

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Associations between partial pressure of oxygen and neurological outcome in out-of-hospital cardiac arrest patients: an explorative analysis of a randomized trial

Affiliations

Associations between partial pressure of oxygen and neurological outcome in out-of-hospital cardiac arrest patients: an explorative analysis of a randomized trial

Authors

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

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