Critically ill patients often require admission to the intensive care unit (ICU). When patients develop organ failures and end up on a ventilator, there are changes in the body's cell function that can increase the risk of poor outcomes. All cells, in order to function normally, have mitochondria, which help them generate energy and transfer vital messages between cells. However, during critical illness, the mitochondria in the cells can function less effectively and die prematurely, or their new synthesis and regeneration can be severely affected. This can result in continuous multi-organ failure with a lack of recovery and muscle wasting, causing severe weakness and an inability to function normally.
In this study, the investigators aim to assess mitochondrial capacity using three methods with varying levels of invasiveness. The investigators are planning to recruit 20 patients in the ICU who are on a ventilator for breathing support. The investigators plan to measure mitochondrial capacity from a breath test, blood cells, and muscle cells.
The investigators will collect breath samples after consuming an amino acid, which is a component of protein in our body and is commonly found in food. This amino acid is only broken down by the mitochondria. This safe test allows us to measure how much mitochondrial capacity remains in the body after the modified amino acid is broken down by the mitochondria. In comparison, the investigators will use standard methods which includes blood tests and muscle biopsy to examine the mitochondrial function of platelets (blood cells) and muscle cells. The investigators will also use non-invasive techniques (ultrasound and 'MyotonPRO') to assess muscle.
This study will help us determine the best way to assess mitochondrial function and capacity in critically ill patients and to understand strengths and weaknesses of different approaches.
When patients' mitochondrial function or capacity is impaired, the investigators can provide them with particular nutrition to improve mitochondrial activity. Because evaluating this at the bedside is challenging, it is impossible to tell which patients may benefit from specific therapies that improve mitochondrial function. If this breath test provides an assessment similar to the standard, sophisticated mitochondrial testing, the investigators could use it at the bedside in the future, which may improve patient outcomes and help design large clinical trials.
Adults ≥ 18 years
Mechanically ventilated at time of recruitment
Defined as critically ill by the responsible clinician
Recruited within 48-hours of intubation
Patients < 18 years
Patient is being treated on an end-of-life pathway or active treatment is likely to be withdrawn within 24-hours
Patient has significant liver dysfunction (Child-Pugh ≥ class 3)
Patient is not absorbing enterally (defined as 2 x NG aspirates of > 500ml)