Long-term mortality and health-related quality of life of lower versus higher oxygenation targets in ICU patients with severe hypoxaemia

Elena Crescioli, Thomas Lass Klitgaard, Lone Musaeus Poulsen, Bjørn Anders Brand, Martin Siegemund, Thorbjørn Grøfte, Frederik Keus, Ulf Gøttrup Pedersen, Minna Bäcklund, Johanna Karttunen, Matthew Morgan, Andrei Ciubotariu, Anne-Marie Gellert Bunzel, Stine Rom Vestergaard, Nicolaj Munch Jensen, Thomas Steen Jensen, Maj-Brit Nørregaard Kjær, Aksel Karl Georg Jensen, Theis Lange, Jørn Wetterslev, Anders Perner, Olav Lilleholt Schjørring, Bodil Steen Rasmussen, Elena Crescioli, Thomas Lass Klitgaard, Lone Musaeus Poulsen, Bjørn Anders Brand, Martin Siegemund, Thorbjørn Grøfte, Frederik Keus, Ulf Gøttrup Pedersen, Minna Bäcklund, Johanna Karttunen, Matthew Morgan, Andrei Ciubotariu, Anne-Marie Gellert Bunzel, Stine Rom Vestergaard, Nicolaj Munch Jensen, Thomas Steen Jensen, Maj-Brit Nørregaard Kjær, Aksel Karl Georg Jensen, Theis Lange, Jørn Wetterslev, Anders Perner, Olav Lilleholt Schjørring, Bodil Steen Rasmussen

Abstract

Purpose: We assessed outcomes after 1 year of lower versus higher oxygenation targets in intensive care unit (ICU) patients with severe hypoxaemia.

Methods: Pre-planned analyses evaluating 1-year mortality and health-related quality-of-life (HRQoL) outcomes in the previously published Handling Oxygenation Targets in the ICU trial which randomised 2928 adults with acute hypoxaemia to targets of arterial oxygen of 8 kPa or 12 kPa throughout the ICU stay up to 90 days. One-year all-cause mortality was assessed in the intention-to-treat population. HRQoL was assessed using EuroQol 5 dimensions 5 levels (EQ-5D-5L) questionnaire and EQ visual analogue scale score (EQ-VAS), and analyses were conducted in both survivors only and the intention-to-treat population with assignment of the worst scores to deceased patients.

Results: We obtained 1-year vital status for 2887/2928 (98.6%), and HRQoL for 2600/2928 (88.8%) of the trial population. One year after randomisation, 707/1442 patients (49%) in the lower oxygenation group vs. 704/1445 (48.7%) in the higher oxygenation group had died (adjusted risk ratio 1.00; 95% confidence interval 0.93-1.08, p = 0.92). In total, 1189/1476 (80.4%) 1-year survivors participated in HRQoL interviews: median EQ-VAS scores were 65 (interquartile range 50-80) in the lower oxygenation group versus 67 (50-80) in the higher oxygenation group (p = 0.98). None of the five EQ-5D-5L dimensions differed between groups.

Conclusion: Among adult ICU patients with severe hypoxaemia, a lower oxygenation target (8 kPa) did not improve survival or HRQoL at 1 year as compared to a higher oxygenation target (12 kPa).

Trial registration: ClinicalTrials.gov NCT03174002.

Keywords: Intensive care units; Mortality; Oxygen inhalation therapy; Quality of life; Randomized controlled trial.

Conflict of interest statement

The Dept. of Anaesthesia and Intensive Care, Aalborg University Hospital (EC, BSR, OLS, TLK, AMGB, SRV) receives support for research from the Novo Nordisk Foundation, the Danish Ministry of Higher Education and Science, and AK Pharma. The Dept. of Intensive Care, Rigshospitalet (BB, MNK, AP) receives support for research from the Novo Nordisk Foundation, Sygeforsikringen ‘Danmark’, Pfizer, Fresenius Kabi, and AK Pharma. The Dept. of Anaesthesiology, Zealand University Hospital (LMP, UGP) receives support for research from AK Pharma.

© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.

Figures

Fig. 1
Fig. 1
Patient flow in the HOT-ICU trial. a1 patient in the lower oxygenation group with missing data at 90-day follow-up was included in the -year follow-up. *45/598 (7.5%) were completed by-proxy in the lower oxygenation group and 39/591 (6.6%) in the higher oxygenation group
Fig. 2
Fig. 2
Kaplan–Meier estimates of survival. Shown are the results of Kaplan–Meier analysis of data regarding survival, which was administratively censored at 365 days (adjusted hazard ratio 1.03; 95% confidence interval 0.92–1.14). The Cox proportional-hazards model was adjusted for the trial site, and for the presence or absence of chronic obstructive pulmonary disease and of active haematological malignancy
Fig. 3
Fig. 3
Distribution of EQ-5D-5L among survivors at 1 year from randomisation. EQ-5D-5L denotes EuroQol five dimensions five-level questionnaire [23, 24]. Values are from the responding survivors (n = 598 in the lower oxygenation group; n = 591 in the higher oxygenation group). The corresponding numeric data are presented in Table 2

References

    1. Hypoxemia in the ICU Prevalence, treatment, and outcome. Ann Intensive Care. 2018;8(1):82. doi: 10.1186/s13613-018-0424-4.
    1. Bellani G, 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(8):788–800. doi: 10.1001/jama.2016.0291.
    1. Suzuki S, et al. Current oxygen management in mechanically ventilated patients: a prospective observational cohort study. J Crit Care. 2013;28(5):647–654. doi: 10.1016/j.jcrc.2013.03.010.
    1. Young PJ, et al. Oxygenation targets, monitoring in the critically ill: a point prevalence study of clinical practice in Australia and New Zealand. Crit Care Resusc. 2015;17(3):202–207.
    1. Girardis M, Alhazzani W, Rasmussen BS. What's new in oxygen therapy? Intensive Care Med. 2019;45(7):1009–1011. doi: 10.1007/s00134-019-05619-9.
    1. Helmerhorst HJ, et al. Bench-to-bedside review: the effects of hyperoxia during critical illness. Crit Care. 2015;19(1):284. doi: 10.1186/s13054-015-0996-4.
    1. Chow CW, et al. Oxidative stress and acute lung injury. Am J Respir Cell Mol Biol. 2003;29(4):427–431. doi: 10.1165/rcmb.F278.
    1. Petersson J, Glenny RW. Gas exchange and ventilation–perfusion relationships in the lung. Eur Respir J. 2014;44(4):1023–1041. doi: 10.1183/09031936.00037014.
    1. Roussos C, Koutsoukou A. Respiratory failure. Eur Respir J. 2003;22(Suppl. 47):3s–14s. doi: 10.1183/09031936.03.00038503.
    1. Thomson AJ, et al. Oxygen therapy in acute medical care. BMJ. 2002;324(7351):1406–1407. doi: 10.1136/bmj.324.7351.1406.
    1. Girardis M, et al. Effect of conservative vs conventional oxygen therapy on mortality among patients in an intensive care unit: the oxygen-ICU randomized clinical trial. JAMA. 2016;316(15):1583–1589. doi: 10.1001/jama.2016.11993.
    1. Asfar P, et al. Hyperoxia and hypertonic saline in patients with septic shock (HYPERS2S): a two-by-two factorial, multicentre, randomised, clinical trial. Lancet Respir Med. 2017;5(3):180–190. doi: 10.1016/S2213-2600(17)30046-2.
    1. Mackle D, et al. Conservative oxygen therapy during mechanical ventilation in the ICU. N Engl J Med. 2020;382(11):989–998. doi: 10.1056/NEJMoa1903297.
    1. Barrot L, et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Engl J Med. 2020;382(11):999–1008. doi: 10.1056/NEJMoa1916431.
    1. Schjørring OL, et al. Lower or higher oxygenation targets for acute hypoxemic respiratory failure. N Engl J Med. 2021;384(14):1301–1311. doi: 10.1056/NEJMoa2032510.
    1. Gelissen H, et al. Effect of low-normal vs high-normal oxygenation targets on organ dysfunction in critically ill patients: a randomized clinical trial. JAMA. 2021;326:940. doi: 10.1001/jama.2021.13011.
    1. Gaudry S, et al. Patient-important outcomes in randomized controlled trials in critically ill patients: a systematic review. Ann Intensive Care. 2017;7(1):28. doi: 10.1186/s13613-017-0243-z.
    1. Hammond NE, et al. Health-related quality of life in survivors of septic shock: 6-month follow-up from the ADRENAL trial. Intensive Care Med. 2020;46(9):1696–1706. doi: 10.1007/s00134-020-06169-1.
    1. Schjørring OL, et al. The handling oxygenation targets in the intensive care unit (HOT-ICU) trial: detailed statistical analysis plan. Acta Anaesthesiol Scand. 2020;64(6):847–856. doi: 10.1111/aas.13569.
    1. Schjørring OL, et al. Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU)—protocol for a randomised clinical trial comparing a lower vs a higher oxygenation target in adults with acute hypoxaemic respiratory failure. Acta Anaesthesiol Scand. 2019;63(7):956–965.
    1. Schulz KF, Altman DG, Moher D. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials. BMC Med. 2010;8:18. doi: 10.1186/1741-7015-8-18.
    1. Schmidt M, Pedersen L, Sørensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014;29(8):541–549. doi: 10.1007/s10654-014-9930-3.
    1. Janssen MF, Bonsel GJ, Luo N. Is EQ-5D-5L better than EQ-5D-3L? A head-to-head comparison of descriptive systems and value sets from seven countries. Pharmacoeconomics. 2018;36(6):675–697. doi: 10.1007/s40273-018-0623-8.
    1. Herdman M, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L) Qual Life Res. 2011;20(10):1727–1736. doi: 10.1007/s11136-011-9903-x.
    1. van Hout B, et al. Interim scoring for the EQ-5D-5L: mapping the EQ-5D-5L to EQ-5D-3L value sets. Value Health. 2012;15(5):708–715. doi: 10.1016/j.jval.2012.02.008.
    1. Vincent JL, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707–710. doi: 10.1007/BF01709751.
    1. Jakobsen JC, et al. Thresholds for statistical and clinical significance in systematic reviews with meta-analytic methods. BMC Med Res Methodol. 2014;14:120. doi: 10.1186/1471-2288-14-120.
    1. Klitgaard TL, et al. Lower versus higher oxygenation targets in critically ill patients with severe hypoxaemia: secondary Bayesian analysis to explore heterogeneous treatment effects in the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial. Br J Anaesth. 2022;128(1):55–64. doi: 10.1016/j.bja.2021.09.010.
    1. Young P, et al. Conservative oxygen therapy for mechanically ventilated adults with sepsis: a post hoc analysis of data from the intensive care unit randomized trial comparing two approaches to oxygen therapy (ICU-ROX) Intensive Care Med. 2020;46(1):17–26. doi: 10.1007/s00134-019-05857-x.
    1. Suran M. Preparing hospitals' medical oxygen delivery systems for a respiratory "Twindemic". JAMA. 2022;327(5):411–413. doi: 10.1001/jama.2021.23392.
    1. Rasmussen BS, et al. Oxygenation targets in ICU patients with COVID-19: a post hoc subgroup analysis of the HOT-ICU trial. Acta Anaesthesiol Scand. 2022;66(1):76–84. doi: 10.1111/aas.13977.
    1. Jensen MB, et al. Danish population health measured by the EQ-5D-5L. Scand J Public Health. 2021 doi: 10.1177/14034948211058060.
    1. Dowdy DW, et al. Quality of life after acute respiratory distress syndrome: a meta-analysis. Intensive Care Med. 2006;32(8):1115–1124. doi: 10.1007/s00134-006-0217-3.
    1. Herridge MS, et al. Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med. 2011;364(14):1293–1304. doi: 10.1056/NEJMoa1011802.
    1. Mikkelsen ME, et al. The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med. 2012;185(12):1307–1315. doi: 10.1164/rccm.201111-2025OC.
    1. Angus DC, Carlet J. Surviving intensive care: a report from the 2002 Brussels Roundtable. Intensive Care Med. 2003;29(3):368–377. doi: 10.1007/s00134-002-1624-8.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren