Is too much oxygen a bad thing? A review of hyperoxia and its consequences

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Picture of Komal Parikh
Komal Parikh

I am a Pulmonary and Critical Care Physician with a love for teaching people from all walks of life through my instagram page @pulmcritdoc. I enjoy brunching, working out, pumpkin spice lattes and everything basic in between, all while nerding out over resuscitation, airway, and anything to do with lungs.

The Pre-brief

Have you ever walked by a patient’s room that is on 2 liters/min oxygen via nasal cannula, saturating 100% and thought, “why are they even on oxygen?” Or have you been in the intensive care unit and had a patient on 100% FiO2 on the ventilator saturating 100% and thought, “I’ll wean down the FiO2 when everything else gets better.” If you answered yes to the first question, you’re arriving at an important concept. If you answered yes to the second question, this review will help you understand the thought processes behind a theory that hyperoxia can potentially be damaging to our patients.

Intro:

Oxygen was introduced into anesthesiology practice in the 1930s, and it is now one of the most widely used “drugs” in hospitalized patients. Up to 86% of hospitalized patients receive some sort of oxygen therapy – whether it is via nasal cannula or mechanical ventilation. Providing supplemental oxygen increases oxygen delivery in HYPOXEMIC patients, but it can actually damage tissues in NON-HYPOXEMIC patients.

Hyperoxia is a state where the cells and tissues of the body are exposed to an excessive amount of oxygen, usually from oxygen supplementation via nasal cannula or mechanical ventilation. This increases the partial pressure of arterial oxygen (PaO2). There have been multiple studies and evidence that have adjusted guidelines based on hypoxemic states, but there are no guidelines that give recommendations on how to avoid or manage hyperoxia. We will review several studies and articles that have been published in the recent years outlining the data behind the effects of hyperoxia and how this affects patient mortality and outcomes. First, let’s get into the pathophysiology. 

Pathophysiology behind hyperoxia:

While the biochemistry and physiological pathways bring back nightmares from our science classes, it is important to review the role oxygen plays at a cellular level to further understand the damage it can potentially do in our patients.

  • Oxygen produces reactive oxygen species (ROS) that increases cell apoptosis, or cell death by directly damaging the mitochondria, which we know as the “powerhouse” of the cell.
  • Oxygen produces damage-associated molecular pattern molecules (DAMPs) that stimulate an inflammatory response in the lungs, which damages the alveolar epithelial cells and thus perpetuates a vicious cycle of producing more inflammatory cytokines.
  • Another important pathophysiologic process is that of nitric oxide (NO). It is produced by L-arginine and oxygen molecules and it is significantly increased in states of hyperoxia induced lung injury, but it is unclear how. Excessive NO from high amounts of oxygen can trigger the cell apoptotic pathway.

Evidence:

Below are studies that have been done examining hyperoxia and how this can affect our patients:

  • The most recent study was published in the New England Journal of Medicine in January 2021. It was a multicenter trial of 2928 patients who were admitted to the ICU and were receiving at least 10 liters/minute of oxygen or a fraction of inspired oxygen of at least 0.5. The patients were randomized to target a PaO2 of 60 mm Hg vs 90 mm Hg. The primary outcome was death within 90 days. What they found was that targeting a lower oxygen target (60 mm Hg) did not increase mortality compared to targeting an oxygen concentration at 90 mm Hg. Rather, they found that there was no difference, even after adjusting for baseline factors. 
  • An observational, retrospective, single center study in France in 2018 examined hyperoxia and mortality as well. They had a total of 130 patients and examined the number of hyperoxia events during their hospital stay, as defined by partial pressure of arterial oxygen greater than 100 mm Hg. They found that overall survival was lower in patients who had at least one episode of hyperoxia during their ICU stay (89% vs 52%).  
  • An observational study of 688 patients done in the emergency department and intensive care unit of an academic center in the United States in 2018 found that hyperoxia increased mortality.  The study organized patients into three oxygen exposure groups based on PaO2 values obtained in the ED after intubation: hypoxia (PaO2 <60 mmhg), normoxia (PaO2 60-120 mmhg), and hyperoxia (PaO2 > 120 mm Hg). ED normoxia occurred in 350 (50.9%) patients, and hyperoxia occurred in 300 (43.6%). Patients with ED hyperoxia had greater hospital mortality (29.7%), when compared to those with normoxia (19.4%) and hypoxia (13.2%) even after adjusting for covariates.  
  • A meta-analysis done in 2009 looked at hyperoxia (PaO2 between 273 – 425 mm Hg) and it’s effects on coronary blood flow. They discovered that there was a significant reduction in coronary blood flow with higher levels of PaO2. Hyperoxia caused a significant increase in coronary vascular resistance and a significant reduction in myocardial oxygen consumption  as well. 

Caveats:

While I will not cover the strengths and limitations of each of these studies in this review, I will say that most of the information that we have available showing hyperoxia is “bad” are observational or retrospective studies. I do urge our CCN readers to read these studies on their own. Every study has its own limitations, which is why it is important to understand the physiology behind oxygen therapy and how it can be harmful or beneficial in patients, depending on the physiological process that is happening.

The Debrief

As we try to minimize the medications and drips patients get in the intensive care unit, we should also work to minimize the amount of oxygen patients receive. Make titrating down the FiO2 a daily practice of yours and your team, and always remember that oxygen supplemental is a “drug” that is VERY commonly used in the ICU!

References

  1. Bellomo, R. et al. Arterial hyperoxia and in-hospital mortality after resuscitation from cardiac arrest. Crit Care 15, R90 (2011).
  2. Farquhar, H. et al. Systematic review of studies of the effect of hyperoxia on coronary blood flow. Am Heart J 158, 371–377 (2009).
  3. Ruggiu, M. et al. Hyperoxia effects on intensive care unit mortality: a retrospective pragmatic cohort study. Crit Care 22, 218 (2018).
  4. Schjorring, O. et al. Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure. N Engl J Med (2021). 
  5. Zou, D. et al. Reactive oxygen and nitrogen species induce cell apoptosis via a mitochondria‐dependent pathway in hyperoxia lung injury. J Cell Biochem 120, 4837–4850 (2019).

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