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 Table of Contents  
Year : 2021  |  Volume : 23  |  Issue : 2  |  Page : 225-227

Oxygen therapy: How much is too much

1 Department of Anaesthesiology and Critical Care, Armed Forces Medical College, Pune, Maharashtra, India
2 Commandant, BH, Barrackpore (Brig Rangraj Setlur), Base Hospital, Barrackpore, West Bengal, India

Date of Submission25-Sep-2021
Date of Acceptance25-Sep-2021
Date of Web Publication13-Oct-2021

Correspondence Address:
Col (Dr) Nikahat Jahan
Department of Anaesthesiology and critical Care Armed Forces Medical College, Wanowrie Road, Pune - 411 040, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jmms.jmms_123_21

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How to cite this article:
Jahan N, Setlur R. Oxygen therapy: How much is too much. J Mar Med Soc 2021;23:225-7

How to cite this URL:
Jahan N, Setlur R. Oxygen therapy: How much is too much. J Mar Med Soc [serial online] 2021 [cited 2021 Nov 28];23:225-7. Available from: https://www.marinemedicalsociety.in/text.asp?2021/23/2/225/328151

Oxygen therapy is one of the most common interventions in critically ill patients and has been the focus of increased attention since the coronavirus disease (COVID) pandemic began. Oxygen should be treated like a drug and must be prescribed with a proper dose, that is, flowrate, duration, and the technique and targets should be specified clearly, for example, “Give Oxygen by NRBM @ 6 l/min, titrate to target a SpO2 of 92%–94% or a PaO2 of 60 mmHg or greater.” This is because giving either too much or too little oxygen may be harmful.

While oxygen is essential for life, too much oxygen is toxic. Excess oxygen causes formation of free radicals which cause tissue damage in the form of acute lung injury as well as causing coronary and cerebral vasoconstriction and absorption atelectasis.

It is extremely important to understand the importance of the sigmoid shape of the oxygen dissociation curve [Figure 1]. The saturation of Haemoglobin is 90% at a PaO2 of 60 mmHg. Beyond this point the curve plateaus, requiring a large increase in PaO2 to achieve marginal increases in SpO2. The excess oxygen required to make marginal improvements in SpO2 could lead to harmful effects without corresponding benefits. Whether these concerns are real in regular clinical practice or largely of theoretical concern is a question which has been studied in various subgroups.
Figure 1: The oxygen dissociation curve[15]

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Barrot et al. conducted a multicenter randomized control trial (RCT) to compare liberal versus conservative oxygen therapy for ARDS (LOCO study). They tested the acute respiratory distress syndrome (ARDS) net studies recommendation of targeting a PaO2 55–80 mmHg (SpO2 88%–92%) for patients with ARDS against a liberal oxygen therapy target PaO2 of 90–105 mmHg (Spo2 ≥96%) for 7 days. Mechanical ventilation strategies used in both groups were similar. The primary outcome was death from any cause at 28 days. The study was stopped prematurely by the data and safety monitoring board because of safety concerns and a low likelihood of a significant difference between the two groups. Five cases of mesenteric ischemia occurred in the conservative group. They concluded that in ARDS patients, early exposure to conservative oxygen therapy did not increase survival at 28 days, although the mortality was higher at 90 days in the conservative oxygen group.[1]

A European multinational study, Handling Oxygen Targets in Intensive Care Units (HOT-ICU trial) which included 2928 patients, published in 2021, considered whether lower (PaO2 60 mmHg) versus Higher Oxygenation (PaO2 90 mmHg) targets reduce mortality in patients of hypoxemic respiratory failure. They found no difference in the primary outcome of all-cause mortality at 90 days. They concluded that “among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days.”[2] This study also did not show any adverse events in the conservative oxygen group, in contrast to the LOCO study

Another randomized control trial, ICU-ROX conducted in Australia and New Zealand, published in 2019, studied whether a conservative use of oxygen therapy compared to usual oxygen therapy affected the number of ventilator-free days in mechanically ventilated ICU patients. They found no difference in ventilator-free days between the two groups at the end of 28 days in the ICU.[3]

Girardis et al. from Italy published the OXYGEN ICU trial in 2016 where they studied the effect of conservative versus conventional oxygen therapy on mortality among patients in an ICU. The conservative group targeted a PaO2 between 70 and 100 mmHg or arterial oxyhemoglobin saturation (SpO2) between 94% and 98%, while the conventional group targeted PaO2 values up to 150 mmHg or SpO2 values between 97% and 100%. The study was terminated early due to difficulties in enrolment after inclusion of 480 patients. The researchers concluded that with the available data, among critically ill patients with an ICU length of stay of 72 h or longer, a conservative protocol for oxygen therapy versus conventional therapy was associated with lower ICU mortality.[4]

Recently, Gelissen et al. published their findings in JAMA where they found that among critically ill patients with two or more SIRS criteria, treatment with a low-normal PaO2 target compared with a high-normal PaO2 target did not result in a statistically significant reduction in organ dysfunction.[5]

Panwar et al. studied 103 patients likely to require intermittent mandatory ventilation for greater than or equal to 24 h and randomly allocated them to either a conservative oxygenation strategy with target oxygen saturation as measured by pulse oximetry (SpO2) of 88%–92% or a liberal oxygenation strategy with target SpO2 of greater than or equal to 96%. There were no significant between-group differences in any measures of new organ dysfunction, or ICU or 90-day mortality.[6]

In an editorial in AJRCCM, Paul and Bellomo have discussed the rational use of oxygen therapy in different clinical situations and emphasize the point that while hypoxia is detrimental universally, hyperoxemia may be detrimental in a large number but not all clinical conditions.[7]

In the Improving Oxygenation Therapy in Acute Illness (IOTA study), which included 25 randomized controlled trials that enrolled a total of 16,037 patients with sepsis, critical illness, stroke, trauma, myocardial infarction (MI), or cardiac arrest, and patients who had emergency surgery, the conclusion was that in acutely ill adults, high-quality evidence shows that liberal oxygen therapy increases mortality without improving other patient-important outcomes. They concluded that supplemental oxygen might become unfavorable above a SpO2 range of 94%–96% and supported the conservative administration of oxygen therapy.[8]

AVOID study demonstrated no benefit of giving oxygen to normoxic patients with ST-segment elevation MI (STEMI) undergoing percutaneous coronary intervention.[9] DETO2X study showed no difference in 1-year mortality between room air and oxygen therapy groups in normoxic patients with suspected MI.[10]

In the past few years, we have seen that trends in critical care have moved toward a philosophy of “restrictive rather than liberal.” The results of this philosophy have been mixed; the evidence for a restrictive strategy has been fairly strong in hemoglobin levels, mixed in the speed of fluid restriction, and negative in blood glucose control.[11],[12],[13] It is partly because of this that the 2021 European Resuscitation Council and European Society of Intensive Care Medicine guidelines on postcardiac arrest care after ROSC= Return Of Spontaneous Circulation recommend that once SpO2 can be measured reliably or arterial blood gas values are obtained, the inspired oxygen should be titrated to achieve an arterial oxygen saturation of and 94-98% or arterial partial pressure of oxygen (PaO2) of 75–100 mmHg.[14],[15] However, although it is also the bias of the authors of this article that a conservative strategy should be used for oxygen therapy, the brief review above shows that hard evidence that moderate hyperoxia consistently causes harm in critically ill adult patients has been sparse.

Is hyperoxemia always bad? The answer is No. There are situations where we need an excess of oxygen to treat patients. We use hyperbaric oxygen for the treatment of necrotizing fasciitis, high-altitude pulmonary edema in mountaineers and soldiers, and decompression sickness in divers. We also use high-flow oxygen in the treatment of pneumocephalus and small pneumothoraces. The danger of being too conservative or restrictive in giving oxygen is that there may be episodes of hypoxemia which may be associated with adverse events such as the five cases of mesenteric ischemia in the LOCO study where the restrictive strategy targeted a PaO2 of 55–70 mmHg in the restrictive group.

It is also important to note that in certain groups, hyperoxemia has been associated with harm in RCTs in subgroups of patients with hypoxemic ischemic encephalopathy, STEMI, suspected MI, ARDS, and stroke.

What does all this mean to our daily practice in the ICU, ED, and OT? It means that hypoxia is definitely harmful but hyperoxemia (defined for the purposes of this article as a SpO2 >94%–96% or PaO2 >60–90 mmHg) could probably also be harmful in certain groups of patients. Therefore, oxygen should be given in titrated amounts and the flowmeters or set FiO2 on the ventilators should be turned down as and when the SpO2 is greater than 94%–96%. However, when using conservative oxygen strategies, close monitoring is required to avoid inadvertent episodes of hypoxemia which would be harmful to the patient. Judicious use of oxygen will also go a long way in avoiding oxygen shortages in times of respiratory illness pandemics such as the COVID-19.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Barrot L, Asfar P, Mauny F, Winiszewski H, Montini F, Badie J, et al. Liberal or conservative oxygen therapy for acute respiratory distress syndrome. N Engl J Med 2020;382:999-1008.  Back to cited text no. 1
Schjørring OL, Klitgaard TL, Perner A, Wetterslev J, Lange T, Siegemund M, et al. HOT-ICU Investigators. Lower or higher oxygenation targets for acute hypoxemic respiratory failure. N Engl J Med 2021;384:1301-11.  Back to cited text no. 2
ICU-ROX Investigators and the Australian and New Zealand Intensive Care Society Clinical Trials Group, Mackle D, Bellomo R, Bailey M, Beasley R, Deane A, Eastwood G, et al. Conservative oxygen therapy during mechanical ventilation in the ICU. N Engl J Med 2020;382:989-98.  Back to cited text no. 3
Girardis M, Busani S, Damiani E, Donati A, Rinaldi L, Marudi A, 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;316:1583-9.  Back to cited text no. 4
Gelissen H, de Grooth HJ, Smulders Y, Wils EJ, de Ruijter W, Vink R, et al. Normal vs. high-normal oxygenation targets on organ dysfunction in critically Ill patients: A randomized clinical trial. JAMA 2021;326:940-8.  Back to cited text no. 5
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.  Back to cited text no. 6
Young PJ, Bellomo R. The risk of hyperoxemia in ICU patients. Much Ado About O2. Am J Respir Crit Care Med 2019;200:1333-5.  Back to cited text no. 7
Chu DK, Kim LH, Young PJ, Zamiri N, Almenawer SA, Jaeschke R, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): A systematic review and meta-analysis. Lancet 2018;391:1693-705.  Back to cited text no. 8
Stub D, Smith K, Bernard S, Nehme Z, Stephenson M, Bray JE, et al. Air versus oxygen in ST-Segment–Elevation Myocardial Infarction. Circulation 2015;131:2143-50.  Back to cited text no. 9
Hofmann R, James SK, Svensson L, Witt N, Frick M, Lindahl B, et al. DETermination of the role of oxygen in suspected Acute Myocardial Infarction trial. Am Heart J 2014;167:322-8.  Back to cited text no. 10
Hébert PC. Transfusion requirements in critical care (TRICC): A multicentre, randomized, controlled clinical study. Transfusion Requirements in Critical Care Investigators and the Canadian Critical care Trials Group. Br J Anaesth 1998;81 Suppl 1:25-33.  Back to cited text no. 11
Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, et al. Mortality after fluid bolus in African children with severe infection. N Engl J Med 2011;364:2483-95.  Back to cited text no. 12
Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, et al. Intensive insulin therapy and mortality among critically ill patients: A meta-analysis including NICE-SUGAR study data. CMAJ 2009;180:821-7.  Back to cited text no. 13
Nolan JP, Sandroni C, Böttiger BW, Cariou A, Cronberg T, Friberg H, et al. European Resuscitation Council and European Society of Intensive Care Medicine guidelines 2021: Post-resuscitation care. Intensive Care Med 2021;47:369-421.  Back to cited text no. 14


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