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Disease and treatment

Danish research will set the direction for oxygen therapy

The oxygen therapy given to acutely ill patients internationally is quite inconsistent, with few guidelines and little evidence about what works best. Danish researchers and doctors will now put an end to this.

Although many patients with various diseases receive oxygen therapy, there is no scientific evidence about the optimal method for critically ill patients in intensive care units.

How much should patients get? Which patients will benefit the most, and will any be directly harmed?

Researchers and doctors from Denmark will now answer these questions in the largest study to date on oxygen therapy for critically ill patients with acute respiratory failure.

The answers the Danish researchers and doctors find will set the direction for using oxygen therapy in all intensive care units globally.

“Both the Danish and international guidelines will be set based on our results. They will set a precedent and can hopefully help to save lives and ensure that acutely ill people who are hospitalized have optimal opportunities to recover from their illness with fewer adverse physical and cognitive effects,” explains a researcher behind the new study, Bodil Steen Rasmussen, Clinical Professor and Consultant at Aalborg University Hospital.

The researchers have just recruited the last of almost 3,000 participants into their randomized clinical trial and have published the protocol in Acta Anaesthesiologica Scandinavia.

Oxygen is a drug that can cause adverse effects

Many people do not think of oxygen as a drug.

But like other drugs, oxygen can help patients if given in the right amounts, but it can also cause serious adverse effects if patients get too much.

Nevertheless, there are no clear international guidelines on oxygen therapy, and doctors have some leeway on the amount of oxygen they find most appropriate to treat patients.

This is true even though doctors cannot find evidence in the scientific literature that the amount of oxygen they choose to use is optimal.

There are also great international differences in how much oxygen is given, with the United States and southern Europe especially being very liberal in using oxygen for their patients in intensive care units.

Doctors in Denmark’s intensive care units usually use significantly lower oxygen concentrations.

“But virtually no evidence indicates whether clinicians in Denmark or the United States are doing the right thing,” says Bodil Steen Rasmussen.

Both too little and too much oxygen can be dangerous

The problem with giving too much or too little oxygen is that it can harm the patient.

Oxygen can save the lives of critically ill patients with acute respiratory failure: without oxygen, they will die within minutes. If doctors give too little oxygen so that the oxygen saturation in the blood remains low over a long period of time, this can result in multiorgan failure and for those who survive the low oxygen saturation can harm the patient’s brain and cognitive ability, and the patient may have memory problems or difficulty concentrating – a type of mild brain damage.

Conversely, if a patient gets too much oxygen and, for example, has severe pneumonia, the extra oxygen in the lungs can be like blowing on embers, and the infection can then get out of control with further destruction of lung tissue and can even be fatal.

“The international guidelines say that clinicians should target oxygen saturation at the lower end of the normal range for severe acute respiratory failure, but no evidence indicates this, nor does any evidence indicate whether this is better than targeting oxygen saturation at the high end of the normal range to reduce the long-term effects of low oxygen saturation. This is why determining this correctly is so important,” explains Bodil Steen Rasmussen.

Almost 3,000 participants

The study involves 2,928 critically ill patients with acute respiratory failure in 36 intensive care units in Denmark, Norway, Finland, Iceland, the Netherlands, Switzerland and the United Kingdom.

The trial participants, who are acutely hospitalized for such diseases as pneumonia, COVID-19, trauma or chronic obstructive pulmonary disease, are affected such that they need to receive at least 10 litres of oxygen through a nasal catheter or 50% oxygen if they are in a ventilator.

The participants will be randomized to receive oxygen inhalation therapy targeting oxygen saturation in the blood either at the high end or at the low end of the normal spectrum.

The researchers and doctors will then examine survival 90 days after hospitalization in the two groups.

About 25–30% of such patients in an intensive care unit die, and Bodil Steen Rasmussen expects that this percentage could be reduced by doing things right.

“We could perhaps save the lives of up to 5% of patients,” she says.

Doctors have changed their attitudes in the past 5 years

In addition to determining whether the patients survive or die, the researchers will also investigate whether oxygen inhalation therapy harms the patients.

There may be a risk that some patients being treated with too little oxygen develop cognitive dysfunction even if they survive.

Some patients may also survive but have received so much oxygen that their lung infection causes lasting damage.

Bodil Steen Rasmussen says that doctors are focusing on this and that guidelines are clearly needed that have been established based on the type of trial the researchers from Aalborg University Hospital are carrying out.

“Regardless of specialty, clinicians have become more aware of this in recent years. In the old days, all patients received oxygen in the ambulance and after surgery. Now we have become aware that not giving oxygen is often better if this can be avoided, because oxygen can also harm the patient. Now we just have to figure out how much we then need to give,” adds Bodil Steen Rasmussen.

COVID-19 Examining patients with COVID-19

The doctors will also examine subgroups of patients in their trial.

This may include examining how high or low oxygen saturation affects patients with chronic obstructive pulmonary disease or in relation to the severity of the disease.

Finally, the doctors are also launching a separate trial to investigate how oxygen therapy affects patients with COVID-19.

The current study involves 100 patients with COVID-19, but the researchers would like to include more in a larger study so that they can determine for this specific patient group how much oxygen the patients need to optimally survive the disease with the fewest possible adverse effects.

“We will also follow up this patient group for a long period and see how oxygen therapy affects their cognitive and lung functioning in the long term,” explains Bodil Steen Rasmussen.

Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) – protocol for a randomised clinical trial comparing a lower vs a higher oxygenation target in adults with acute hypoxaemic respiratory failure” has been published in Acta Anaesthesiologica Scandinavica. In 2018, the Novo Nordisk Foundation awarded a grant to Bodil Steen Rasmussen for the project Long-term Cognitive and Pulmonary Effects of Different Handling of Oxygenation in ICU Patients-the LONG-HOT trial.

Bodil Steen Rasmussen
Clinical Professor and Consultant
The Department of Clinical Medicine was established on January 1st, 2013. The department has its physical location at Aalborg University Hospital where research, education and clinic are in direct correlation with each other. The department houses the medical degree program. The Department of Clinical Medicine is affiliated with about 40 research units, each with their own specialty. Many of the research units are organized in a number of interdisciplinary research collaborations within the major research areas such as cardiovascular disease, cancer and neurological conditions