Everest to intensive care: using oxygen safely and well
Low oxygen (hypoxia) is harmful and ultimately fatal. Giving oxygen has been fundamental to surgical and critical care for decades.
Despite this, and oxygen’s toxicity at high levels, little evidence underpins its use. Our hypoxia research is changing this, driving better targeted oxygen therapy for patients.
It is important to deliver just the right amount of oxygen to critical care patients – either too much or too little can be harmful. Yet little evidence underpins its use.
We explored how the body responds to too little oxygen through Xtreme Everest. Two expeditions climbed through the oxygen-depleted air of Everest.
We went on to apply this knowledge to treat critical illness with targeted oxygen therapy.
Just the right amount
Hypoxia in critical illness injures organs like the brain and heart, stopping them functioning.
Yet too much oxygen (hyperoxia) results in toxic molecules being produced (reactive oxygen species, ROS). These ROS molecules damage organs, most commonly the lungs ('oxidative stress').
People’s response to hypoxia varies, which may impact their survival and recovery from illness. Understanding these differences and their causes is key to giving individuals just the right amount of oxygen.
Scaling Mount Everest for research
We explored this through the Xtreme Everest hypoxia research programme. That saw two expeditions climbing through the increasingly oxygen-depleted air of Everest.
Blood and muscle samples were taken from team members at points up to the summit. These were analysed for changes in mitochondria, the cells’ powerhouses.
We also looked at which genes were switched on or off and levels of different proteins. Finally, we looked for the toxic ROS molecules.
How our bodies respond to low oxygen
The results showed reduced mitochondrial activity in response to hypoxia (published here).
Further studies confirmed lower protein production and higher breakdown of mitochondria (autophagy) in hypoxia (published here).
We also compared the mitochondria of mountain-living Sherpa people and lowlanders. Sherpas’ mitochondria were found to use oxygen more efficiently.
Together, these studies show our tissues switch to more efficient ways of using oxygen and working during hypoxia.
Helping treat critical care patients
We went on to apply this knowledge to treat critical illness.
We reported changes in mitochondrial structure and efficiency in intensive care patients associated with survival (published here). We linked changes in mitochondrial function with reduced fitness after chemotherapy, and went on to reverse these by exercise.
By identifying oxygen levels that support cells without causing harm in common clinical scenarios, we could pilot and trial targeted oxygen therapy in adults.
We also contributed to an equivalent study in children, and have started to explore targeted oxygen therapy during major surgery.
What do we plan to do next?
Over the next five years, we will build on this knowledge to explore the relation between oxidative stress, mitochondrial function and targeted oxygen therapy.
We will study this in resuscitation and critical illness, heart and major general surgery, and acute COVID-19 care and recovery.