By Eric C. Walter, MD, MSc
Pulmonary and Critical Care Medicine, Northwest Permanente and Kaiser Sunnyside Medical Center, Portland, OR
Dr. Walter reports no financial relationships relevant to this field of study.
SYNOPSIS: A pilot study suggests that a conservative oxygenation approach in patients on mechanical ventilation is feasible and may not have adverse consequences.
SOURCE: Panwar R, et al. Conservative versus liberal oxygenation targets for mechanically ventilated patients — a pilot multicenter randomized controlled trial. Am J Respir Crit Care Med 2015 Sept 3 [Epub ahead of print].
Supplemental oxygen is almost universally provided to patients requiring mechanical ventilation, usually to correct some degree of hypoxia. However, there are little data to guide clinicians in determining oxygen saturation goals and the amount of oxygen needed to achieve these goals. With too little oxygen, hypoxia and tissue ischemia are obvious concerns, but there are also increasing concerns about the risks of hyperoxia.
The primary goal of this multicenter, randomized, controlled trial was to determine if it was feasible to perform a randomized controlled study comparing a conservative oxygen therapy strategy (goal pulse oximeter measured saturation [SpO2] of 88-92%) and a liberal oxygen therapy strategy (goal SpO2 ≥ 96%). Secondary outcomes included hypoxia (defined as SpO2 < 88%), measures of organ dysfunction (duration of mechanical ventilation, vasopressor use, serum creatinine, etc.), length of stay, and mortality. Positive end-expiratory pressure (PEEP) was determined by the treating clinicians.
Results showed it was feasible to demonstrate a separation in SpO2 between the two groups. The mean SpO2 in the conservative group was 93% vs 97% in the liberal group (P < 0.001). Mean partial pressure of arterial oxygen (PaO2) also significantly differed: 70 mmHg in the conservative group vs 92 mmHg in the liberal group (P < 0.001). PEEP levels did not differ between groups. Hypoxia was quite rare (1% and 0.3% of time in the conservative and liberal groups, respectively). On the other hand, there was evidence that oxygen was used excessively. Despite having an SpO2 > 98%, patients were receiving supplemental oxygen (FiO2 > 0.21) 22% of the time. There were no other significant differences in any of the measures of organ dysfunction, length of stay, or mortality.
COMMENTARY
The optimal oxygenation target among mechanically ventilated patients is not known. Clearly, we wish to avoid hypoxia, but defining a safe cutoff for hypoxia is challenging. In the landmark acute respiratory distress syndrome network (ARDSNet) low tidal volume study, the goal SpO2 range was 88-95%.1 However, some are beginning to question whether this range is too low and whether mild hypoxemia could be related to the observed poor long-term neurocognitive outcomes of some ICU survivors. Conversely, hyperoxia has been associated with increased mortality in post-cardiac arrest, stroke, and traumatic brain injury patients.2
With these questions in mind, Panwar et al sought to determine if it would be feasible to conduct a study comparing conservative and liberal oxygenation strategies. The authors show this is possible. They were clearly able to show a difference in mean SpO2 between the two groups over the course of an entire ICU. The difference between a mean SpO2 of 93% and 97% is of uncertain clinical significance in any individual patient. However, that was not the objective of the study.
Beyond showing feasibility, the authors reported no evidence of harm with either the conservative or liberal strategy. This is reassuring, but the study was not powered for these outcomes, and this study does not rule out the potential for harm. The rarity of hypoxia was quite striking, especially in the conservative arm where the target SpO2 range was 88-92%. It should be noted that these patients were not overly sick. At the time of enrollment, only 33% of the conservative oxygen group and 20% of the liberal oxygen group had ARDS, and the mean PaO2/FiO2 was approximately 250 in both groups. It is doubtful that hypoxic episodes would have been so rare if patients had more significant ARDS.
A major limitation of this study was that nearly 20% of patients were excluded if their treating clinician felt there was not enough clinical equipoise to enroll a particular patient. This severely limits the generalizability of the study and likely introduced bias. Clinicians may have excluded patients they felt were too sick to be enrolled.
By design, this was a small pilot feasibility study. Given the small size and potential biases, clinicians should be strongly cautioned against using results from this trial to make widespread practice changes. Nevertheless, this study does remind us that oxygen is a treatment to be “prescribed” only when necessary. Frequently, patients receive more supplemental oxygen than needed, and many would do well on less oxygen or even room air.
REFERENCES
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The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301-1308.
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Damiani E, et al. Arterial hyperoxia and mortality in critically ill patients: A systematic review and meta-analysis. Crit Care 2014;18:711.
