Thread by @CritCareReviews

Oxygen is the most abundant chemical element by mass in the Earth’s biosphere and is one of the most used drugs in medicine.
But what are the thresholds for its use in critical care?

A thread...
1/16

Today, oxygen is central to most life on planet earth.
But it wasn't always this way.
As little as 700 million years ago, there was little oxygen on planet earth and most species were anaerobic.

2/16

During the Great Oxidation Event, starting 4 billion years ago, cyanobacteria began to generate oxygen as a byproduct of energy production via photosynthesis.

3/16

Oxygen initially combined with metals in the seafloor, until a saturation point was reached & diatomic oxygen levels rose in the oceans.
This lead to an evolution of aquatic organisms capable of using dissolved oxygen during the Cambrian explosion 540 million years ago

4/16

During the late Devonian period, 420 - 360 million years ago, atmospheric oxygen levels rose and complex life moved from sea to land.
Plants and advanced organisms evolved to directly extract atmospheric oxygen

5/16

The reactivity of oxygen allowed far greater amounts of energy to be generated via oxidative phosphorylation in mitochondria than was previously metabolically possible

6/16

Oxygen's reactivity became an essential defense mechanism too, with invading microbes destroyed by oxidative bursts after being phagocytosed by neutrophils and other immune cells.

via @NIH

7/16

@NIH But the biological use of this element came with a cost, as host cells and tissues were also vulnerable to oxidative damage, requiring an entire redox system to protect against self injury

(10.1001/archsurg.136.10.1201)
8/16

@NIH Although life saving in states of extreme hypoxic respiratory failure, the thresholds for harm from supplemental oxygen have not been determined in critically ill patients

9/16

@NIH Hyperoxia has been associated with injurious mechanisms in many organs and pathologies, but clear harm from mild hyperoxaemia remains uncertain.

(10.1186/s13054-021-03815-y)
10/16

@NIH A fascinating trial in African children with pneumonia suggested possible benefit with mild permissive hypoxia, but was limited by an early termination and failure to achieve it's required sample size

(10.1007/s00134-021-06385-3)
11/16

@NIH Would a restrictive oxygenation approach avoid the potential harms of hyperoxia, or would it subject patients to a lower oxygen level, possibly causing subtle cognitive deficits, especially in older adults?

12/16

@NIH Last year the HOT-ICU trial results were presented at eCCR21 and simultaneously published in @NEJM.
This compared conservative (8kPa) with liberal oxygen (12 kPa) targets in patients with acute hypoxaemic respiratory failure

criticalcarereviews.com/meetings/eccr21
13/16

@NIH @NEJM Clear separation in oxygen exposure was achieved
There was no major difference in the primary outcome of 90 day mortality

(10.1056/NEJMoa2032510)
14/16

@NIH @NEJM But what of longer term outcomes, including cognitive and pulmonary functions?
What is the Goldilocks zone for oxygenation in the critically ill?

15/16

@NIH @NEJM It's time for the LONG-HOT results - the one year outcomes of the HOT-ICU trial.
Join us in June at #CCR22 to find out!

criticalcarereviews.com/meetings/ccr22
16/16

@BodilSRasmussen @AndersPerner @MortenHylander @CRIC_Int_Care @DASAIMdk

@NIH @NEJM @BodilSRasmussen @AndersPerner @MortenHylander @CRIC_Int_Care @DASAIMdk Images from wikipedia and shutterstock