The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study

Edward Palmer; Benjamin Post; Roman Klapaukh; Giampiero Marra; Niall S. MacCallum; David Brealey; Ari Ercole; Andrew Jones; Simon Ashworth; Peter Watkinson; Richard Beale; Stephen J. Brett; J. Duncan Young; Claire Black; Aasiyah Rashan; Daniel Martin; Mervyn Singer; Steve Harris

doi:10.1164/rccm.201904-0849OC

The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study

Edward Palmer, Benjamin Post, Roman Klapaukh, Giampiero Marra, Niall S. MacCallum, David Brealey, Ari Ercole, Andrew Jones, Simon Ashworth, Peter Watkinson, Richard Beale, Stephen J. Brett, J. Duncan Young, Claire Black, Aasiyah Rashan, Daniel Martin, Mervyn Singer, Steve Harris

Inflammation Biology

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Abstract

Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients.Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals.Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95-1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04-1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07-2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11-2.72; P = 0.02). However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.

Original language	English
Pages (from-to)	1373-1380
Number of pages	8
Journal	American Journal of Respiratory and Critical Care Medicine
Volume	200
Issue number	11
DOIs	https://doi.org/10.1164/rccm.201904-0849OC
Publication status	Published - 1 Dec 2019

Keywords

critical care
hyperoxia
logistic models

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10.1164/rccm.201904-0849OC

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Palmer, E., Post, B., Klapaukh, R., Marra, G., MacCallum, N. S., Brealey, D., Ercole, A., Jones, A., Ashworth, S., Watkinson, P., Beale, R., Brett, S. J., Young, J. D., Black, C., Rashan, A., Martin, D., Singer, M., & Harris, S. (2019). The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study. American Journal of Respiratory and Critical Care Medicine, 200(11), 1373-1380. https://doi.org/10.1164/rccm.201904-0849OC

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title = "The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study",

abstract = "Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients.Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals.Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95-1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04-1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07-2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11-2.72; P = 0.02). However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.",

keywords = "critical care, hyperoxia, logistic models",

author = "Edward Palmer and Benjamin Post and Roman Klapaukh and Giampiero Marra and MacCallum, {Niall S.} and David Brealey and Ari Ercole and Andrew Jones and Simon Ashworth and Peter Watkinson and Richard Beale and Brett, {Stephen J.} and Young, {J. Duncan} and Claire Black and Aasiyah Rashan and Daniel Martin and Mervyn Singer and Steve Harris",

year = "2019",

month = dec,

day = "1",

doi = "10.1164/rccm.201904-0849OC",

language = "English",

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pages = "1373--1380",

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Palmer, E, Post, B, Klapaukh, R, Marra, G, MacCallum, NS, Brealey, D, Ercole, A, Jones, A, Ashworth, S, Watkinson, P, Beale, R, Brett, SJ, Young, JD, Black, C, Rashan, A, Martin, D, Singer, M & Harris, S 2019, 'The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study', American Journal of Respiratory and Critical Care Medicine, vol. 200, no. 11, pp. 1373-1380. https://doi.org/10.1164/rccm.201904-0849OC

The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study. / Palmer, Edward; Post, Benjamin; Klapaukh, Roman et al.
In: American Journal of Respiratory and Critical Care Medicine, Vol. 200, No. 11, 01.12.2019, p. 1373-1380.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study

AU - Palmer, Edward

AU - Post, Benjamin

AU - Klapaukh, Roman

AU - Marra, Giampiero

AU - MacCallum, Niall S.

AU - Brealey, David

AU - Ercole, Ari

AU - Jones, Andrew

AU - Ashworth, Simon

AU - Watkinson, Peter

AU - Beale, Richard

AU - Brett, Stephen J.

AU - Young, J. Duncan

AU - Black, Claire

AU - Rashan, Aasiyah

AU - Martin, Daniel

AU - Singer, Mervyn

AU - Harris, Steve

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients.Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals.Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95-1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04-1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07-2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11-2.72; P = 0.02). However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.

AB - Rationale: There is conflicting evidence on harm related to exposure to supraphysiologic PaO2 (hyperoxemia) in critically ill patients.Objectives: To examine the association between longitudinal exposure to hyperoxemia and mortality in patients admitted to ICUs in five United Kingdom university hospitals.Methods: A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.Measurements and Main Results: Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the PaO2 time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio [OR], 1.15; 95% compatibility interval [CI], 0.95-1.38; P = 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04-1.74; P = 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07-2.13; P = 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11-2.72; P = 0.02). However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.Conclusions: An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.

KW - critical care

KW - hyperoxia

KW - logistic models

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U2 - 10.1164/rccm.201904-0849OC

DO - 10.1164/rccm.201904-0849OC

M3 - Article

C2 - 31513754

AN - SCOPUS:85075813095

SN - 1073-449X

VL - 200

SP - 1373

EP - 1380

JO - American Journal of Respiratory and Critical Care Medicine

JF - American Journal of Respiratory and Critical Care Medicine

IS - 11

ER -

The Association between Supraphysiologic Arterial Oxygen Levels and Mortality in Critically Ill Patients. A Multicenter Observational Cohort Study

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