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Effectiveness and Clinical Outcomes of a Two-Step Implementation of Conservative Oxygenation Targets in Critically Ill Patients

A Before and After Trial*

Helmerhorst, Hendrik J. F. MD; Schultz, Marcus J. MD, PhD; van der Voort, Peter H. J. MD, PhD; Bosman, Robert J. MD; Juffermans, Nicole P. MD, PhD; de Wilde, Rob B. P. PhD; van den Akker-van Marle, M. Elske PhD; van Bodegom-Vos, Leti , PhD; de Vries, Marieke PhD; Eslami, Saeid PhD; de Keizer, Nicolette F. PhD; Abu-Hanna, Ameen PhD; van Westerloo, David J. , MD, PhD; de Jonge, Evert MD, PhD

doi: 10.1097/CCM.0000000000001461
Clinical Investigations

Objectives: Conservative oxygen therapy is aimed at the prevention of harm by iatrogenic hyperoxia while preserving adequate tissue oxygenation. Our aim was to study the effectiveness and clinical outcomes of a two-step implementation of conservative oxygenation targets in the ICU.

Design: This was a before and after stepwise implementation study of conservative oxygenation targets, between July 2011 and July 2014. The primary endpoint was the proportion of PaO2 values within the target range. Secondary outcomes included ventilator-free days at day 28, length of stay, and mortality.

Setting: Three closed-format ICUs in the Netherlands.

Patients: We analyzed data on 15,045 eligible admissions.

Interventions: The first implementation phase consisted of providing training and feedback on new guidelines instructing for explicit targets for arterial oxygen tension (PaO2, 55–86 mm Hg) and oxyhemoglobin saturation (SpO2, 92–95%). In the second phase, bedside clinicians were additionally assisted in guideline adherence by a computerized decision-support system.

Measurements and Main Results: The proportion of PaO2 in the target range increased from 47% at baseline to 63% in phase 1 and to 68% in phase 2 (p < 0.0001). Episodes of hyperoxia decreased (p < 0.0001), whereas hypoxic episodes remained unchanged (p = 0.06) during the study. Mechanical ventilation time was significantly lower (p < 0.01) during both study phases. After adjustment for potential confounders, ventilator-free days in phase 1 and phase 2 were higher than baseline: adjusted mean difference, 0.55 (95% CI, 0.25–0.84) and 0.48 (95% CI, 0.11–0.86), respectively. Adjusted ICU mortality and ICU-free days did not significantly differ between study phases. Hospital mortality decreased in reference to baseline: adjusted odds ratio, 0.84 (95% CI, 0.74–0.96) for phase 1 and 0.82 (95% CI, 0.69–0.96) for phase 2.

Conclusions: Stepwise implementation of conservative oxygenation targets was feasible, effective, and seemed safe in critically ill patients. The implementation was associated with several changes in clinical outcomes, but the causal impact of conservative oxygenation is still to be determined.

1Department of Intensive Care Medicine, Leiden University Medical Center, Leiden, The Netherlands.

2Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center, Amsterdam, The Netherlands.

3Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands.

4Department of Intensive Care Medicine, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands.

5TIAS School for Business and Society, Tilburg University, Tilburg, The Netherlands.

6Department of Medical Decision Making, Leiden University Medical Center, Leiden, The Netherlands.

7Department of Social Psychology, Tilburg University, Tilburg, The Netherlands.

8Department of Medical Informatics, Academic Medical Center, Amsterdam, The Netherlands.

9Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

*See also p. 641.

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Trial Registration: Netherlands Trial Register, number NTR3424.

Drs. Helmerhorst, de Wilde, van den Akker-van Marle, van Bodegom-Vos, Abu-Hanna, van Westerloo, and de Jonge’s institutions received grant support from the Netherlands Organization for Health Research and Development (ZonMw). Dr. Bosman consulted for IteMedical, Dutch supplier of the patient data management system (not related to this project). The remaining authors have disclosed that they do not have any potential conflicts of interest.

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