Hyperoxemia in the ICU
Hyperoxemia can be defined as an increase in arterial oxygen partial pressure (PaO2) to a level greater than 120 mmHg (16 kPa) (1, 2). It is considered to be moderate for levels ranging between 120 and 200 mmHg, and severe if PaO2 exceeds 200 mmHg (27 kPa) (3). Hyperoxemia is caused by hyperoxia (an increase in oxygen) and occurs in 22% to 50% of mechanically ventilated patients in the ICU (1, 3-6).
- Hyperoxemia can be defined as an increase in arterial oxygen partial pressure (PaO2) to a level greater than 120 mmHg (16 kPa) and may occur in up to 50% of mechanically ventilated patients.
- Retrospective studies have reported hyperoxemia to be associated with the duration of mechanical ventilation, the ICU stay and the hospital stay, as well as with VAP.
- Avoiding hyperoxemia and targeting physiological ranges of SpO2 and PaO2 in ICU patients may be associated with improved outcomes.
- A closed loop oxygenation controller may support this strategy in mechanically ventilated patients, and also reduce the workload for healthcare staff.
Retrospective studies have reported hyperoxemia to be associated with the duration of mechanical ventilation, of the ICU stay and the hospital stay, as well as with ventilator-associated pneumonia (7, 8). Evidence indicates that conservative management of oxygen using pulse oximetry to target an oxygen saturation (SpO2) of between 90% and 92% is associated with decreased radiological evidence of atelectasis (9). Severe hyperoxemia and the time spent in hyperoxemia are associated with a higher mortality rate and fewer ventilator-free days (3). In a study focusing primarily on oxygenation during the first 24 hours of ICU admission for mechanically ventilated patients, results showed hospital mortality to have a U-shaped relationship with PaO2, whereby both the lower and higher PaO2 values were associated with higher mortality (10).
In 2016, results were published from the first large, prospective randomized controlled trial to test whether a conservative protocol for oxygen supplementation to maintain PaO2 within physiological limits could improve outcomes in ICU patients (11). This single-center, open-label, randomized clinical trial included adult ICU patients with an expected length of stay of at least 72 hours. Exclusion criteria included pregnancy, readmission to the ICU, a decision to withhold life-sustaining treatment, immunosuppression or neutropenia, an exacerbation of COPD, and ARDS with a PaO2/FiO2 ratio below 150 mmHg. Patients were randomized into two groups, one for controlled normoxia (targeting PaO2 of 70-100 mmHg or SpO2 of 94%-98%) and one for usual care (FiO2 of 0.4 or higher as needed, targeting SpO2 of 97%-100% accepting PaO2 values of up to 150 mmHg). The primary outcome was ICU mortality, and secondary outcomes included new-onset organ failure, and bloodstream, respiratory, and surgical-site infections. The study was stopped prematurely after inclusion of 480 patients. The modified intention-to-treat population included 218 patients in the usual-care group and 216 patients in the controlled normoxia group. Sixty percent were surgical ICU patients, mostly admitted with respiratory failure (55%), and 65% of these patients were mechanically ventilated. The daily, time-weighted FiO2 and PaO2 averaged during the ICU stay were higher in the usual-care group than in the controlled normoxia group (median FiO2: 39% (35-42) versus 36% (30-40); median PaO2: 102 mmHg (88-116) versus 87 mmHg (79-97); p<0.001). ICU and hospital mortality were significantly higher in the usual-care group than in the controlled normoxia group (ICU mortality: 20% versus 12%, p=0.01; hospital mortality: 34% versus 24%, p=0.03), as was the occurrence of new shock episodes and liver failure during the ICU stay. The risk of bloodstream infections was also higher in the usual-care group than in the controlled normoxia group, and the number of hours free from mechanical ventilation was lower. There was no difference between the two groups in terms of the length of ICU and hospital stay.
This study shows that avoidance of hyperoxemia is associated with better outcomes, and suggests that clinicians should target physiological ranges of SpO2 and PaO2 in ICU patients. In a pilot, multicenter, randomized controlled trial, a more conservative SpO2 target (88%-92%) was not associated with better outcomes when compared to a normoxia group (12).
Maintaining SpO2 within target ranges for mechanically ventilated patients requires a number of daily manual adjustments. INTELLiVENT-ASV* offers an oxygenation controller that adjusts oxygen and PEEP according to a PEEP/FiO2 table to reach the target SpO2 set by the user. In a pilot randomized controlled trial comparing INTELLiVENT-ASV with conventional ventilation modes (volume control and pressure support) for the full duration of mechanical ventilation in 60 ICU patients, INTELLiVENT-ASV was associated with significantly fewer episodes of hyperoxemia, without increasing the risk of hypoxemia (13). The number of manual oxygen settings was dramatically reduced using INTELLiVENT-ASV when compared to conventional modes (median number of daily manual adjustments: 0 (0-0) versus 3 (1-8), p<0.001) (14).
In conclusion, avoiding hyperoxemia and targeting physiological ranges for PaO2 and SpO2 in ICU patients is associated with improved outcomes. A closed loop oxygenation controller may help clinicians to apply this strategy in mechanically ventilated patients, and also reduce the workload for healthcare staff.
* Not available in the US and some other markets
- De Graaff AE, Dongelmans DA, Binnekade JM, de Jonge E. Clinicians' response to hyperoxia in ventilated patients in a Dutch ICU depends on the level of FiO2. Intensive Care Med 2011 ;37(1):46-51.
- Hafner S, Beloncle F, Koch A, Radermacher P, Asfar P. Hyperoxia in intensive care, emergency, and peri-operative medicine: Dr. Jekyll or Mr. Hyde? A 2015 update. Ann Intensive Care 2015;5:42.
- Helmerhorst HJ, Arts DL, Schultz MJ, van der Voort PH, Abu-Hanna A, de Jonge E, et al. Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care. Crit Care Med 2017;45:187-195. (Abstract only)
- Itagaki T, Nakano Y, Okuda N, Izawa M, Onodera M, Imanaka H, et al. Hyperoxemia in mechanically ventilated, critically ill subjects: incidence and related factors. Respir Care 2015 ;60:335-40.
- Eastwood G, Bellomo R, Bailey M, Taori G, Pilcher D, Young P, et al. Arterial oxygen tension and mortality in mechanically ventilated patients. Intensive Care Med 2012;38:91-8. (Abstract only)
- Suzuki S, Eastwood GM, Peck L, Glassford NJ, Bellomo R. Current oxygen management in mechanically ventilated patients: a prospective observational cohort study. J Crit Care 2013;28:647-54. (Abstract only)
- Rachmale S, Li G, Wilson G, Malinchoc M, Gajic O. Practice of excessive FiO2 and effect on pulmonary outcomes in mechanically ventilated patients with acute lung injury. Respir Care 2012;57:1887-93.
- Six S, Jaffal K, Ledoux G, Jaillette E, Wallet F, Nseir S. Hyperoxemia as a risk factor for ventilator-associated pneumonia. Crit Care 2016;20:195.
- Suzuki S, Eastwood GM, Goodwin MD, Noë GD, Smith PE, Glassford N, et al. Atelectasis and mechanical ventilation mode during conservative oxygen therapy: A before-and-after study. J Crit Care 2015 ;30:1232-7. (Abstract only)
- De Jonge E, Peelen L, Keijzers PJ, Joore H, de Lange D, van der Voort PH, et al. Association between administered oxygen, arterial partial oxygen pressure and mortality in mechanically ventilated intensive care unit patients. Crit Care 2008;12:R156.
- Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi Aet 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;316:1583-1589.
- Panwar R, Hardie M, Bellomo R, Barrot L, Eastwood GM, Young PJ, et al. Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med 2016;193:43-51. (Abstract only)
- A. Garnero, D. Novotni, J. Arnal. Manual versus closed loop control of oxygenation parameters during invasive ventilation: effects on hyperoxemia. Critical Care 2017, 21(Suppl 1):57. (Abstract only)
- Arnal JM, Garnero A, Novotni D, Corno G, Donati SY, Demory D, Quintana G, Ducros L, Laubscher T, Durand-Gasselin J. Closed loop ventilation mode in intensive care unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes. Minerva Anestesiol. 2017 Jul 5. [Epub ahead of print] (Abstract only)
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