Today we're going to take a look at BIOENERGETICS in ICU in this quick Tweetorial :-) #ESICMphysio #FOAMed #FOAMcc
Bioenergetics = biochemistry concerned with the energy involved in making and breaking of chemical bonds in the molecules found in biological organisms. It can also be defined as the study of energy relationships and energy transformations and transductions. #ESICMphysio
Mitochondrial functions incl production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. ncbi.nlm.nih.gov/pmc/articles/P…
As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. #ESICMphysio
We've known about bioenergetics and 'failure' for quite some time. We looked into this in ICU back in 1992: journal.chestnet.org/article/S0012-… #FOAMed #FOAMcc #ESICMphysio
Mitochondrial damage occurs in the acute phase of critical illness, followed by activation of mitochondrial biogenesis in survivors. Hypothesized that bioenergetics failure of skeletal muscle may contribute to the development of ICU-acquired weakness. #ESICMphysio #FOAMed
VS healthy controls, in ICU patients =~50% reduction of the ability of skeletal muscle to synthetize ATP in mitochondria. #ESICMphysio #FOAMed
We also know that mitochondrial respiration in vitro is inhibited in severe illness. The mitochondria are one of the major targets for NO. ncbi.nlm.nih.gov/pmc/articles/P…
Following on from this, early onset hypometabolism and bioenergetic failure characterize critical illness and are related to intracellular HSP72 repression, severity of illness and OUTCOME. We think much of this can be related to NO metabolism. #ESICMphysio #FOAMcc #FOAMed
Within ICU - we also know that citrate can contribute to bioenergetics! icurevisited.com/citrate/ Have a look at this link for more info on CRRT and citrate chemistry. It can be quite high... ncbi.nlm.nih.gov/pubmed/22951019 So we should account for this in our nutrition Rx... #ESICMphysio
There are many mechanisms in the body that lead to neuromuscular INexcitability.... #FOAMed #FOAMcc #ESICMphysio ccforum.biomedcentral.com/articles/10.11… 
Well.. Several clinical studies have shown an assoc of EPS alterations with clinical severity, most notably studies on intensive insulin treatment in surgical and medical ICU patients as well as an association with morbidity and with hospital and 1-year mortality... #ESICMphysio
Interestingly - some scientists also hypothesized that in situations of energy failure the cells may revert to a low energy state, a “hibernation” of the cell, to avoid cell death. Which makes sense (bioplausible) in extremely sick patients #ESICMphysio
All of this - if we were able to identify bioenergetic failure - might provide targets for therapy and interventions to prevent, lessen or reverse such cell failure = ?better outcomes for the patient? #ESICMphysio #FOAMed #FOAMcc
Over the years such hypotheses have driven us to look at the reasons for ATP-depletion and 'nasty chemical' release - and targeting interventions against them such as Vitamin C, E, Uniquinone and statins.... #FOAMed #FOAMcc #ESICMphysio
Interestingly - whilst supplementation of ubiquinone and vitamin E in low concs is rather harmless, high concentrations and long-lasting application have been shown to increase the risk of bleeding in patients due to their anticoagulant effects. #ESICMphysio #FOAMed #FOAMcc
So... 1. Mitochondria play an important role in the development of malfunction of various organs, such as heart, liver, and kidney, in a mode that involves changes in turnovers of ATP, ROS, Ca2+, and release of proapoptotic proteins. #ESICMphysio #FOAMed
2. Cell stress occurring under ischemia or/and inflammation always present in ICU patients compromise mitochondrial function, which contributes greatly to the metabolic changes, resulting in cell dysfunction and death, which in turn cause organ failure. #ESICMphysio #FOAMed
3. We know they contribute to cellular dysfunction and death causing organ failure contributing to fatal outcome of ICU patients. #ESICMphysio
Are we close to having circulating mitochondrial DNA as a biomarker in ICU? journals.plos.org/plosmedicine/a… #ESICMphysio #FOAMed #FOAMcc
In 2011, a paper summarised that "Current therapeutic options include antioxidant therapy, nitric oxide donors, and low-level laser therapy, but further studies are necessary to clarify possible benefits for ICU patients."... did they show anything? ncbi.nlm.nih.gov/pmc/articles/P…
Well... DIETARY nitrates were looked at... alas... no difference... (failed to improve mitochondrial metabolic efficiency, rendering this mechanism implausible for the purported exercise benefits of dietary nitrate supplementation.) #ESICMphysio academic.oup.com/ajcn/article/1…
Interestingly - we are also studying nitrates and mitochondrial changes in Metabolic Syndrome -ncbi.nlm.nih.gov/pmc/articles/P…
Some may not be able to see this content behind its paywall - but it's a good overview of mitrochondria in critical illness: sciencedirect.com/science/articl… #OpenAccess #FOAMed #FOAMcc #ESICMphysio
From this, we know that there are mitochondrial roles in... Sepsis, Lung Disease, Skeletal Muscle Dysfunction, Immune Function, Toxic 'DAMP' release (ncbi.nlm.nih.gov/pubmed/28164521) and beyond. #ESICMphysio
RELEASE of Mitochondrial DNA is known as a trigger of systemic inflammation, damaging multiple organs and determining mortality in the critically ill. #ESICMphysio
Work has been done on looking at vitamin supplemention on the bioenergetic index: ncbi.nlm.nih.gov/pubmed/18158690 #ESICMphysio
How can we FEED mitochondria to improve ICU outcomes? We need to look at the easiest interventions first... primarily diet. clinicalnutritionjournal.com/article/S0261-… #ESICMphysio #FOAMed #FOAMcc
It's also important to consider vitamin C's role... but as of yet no good evidence shows it is effective at changing ICU outcomes... BUT - we're in a position where we may soon have more systematic reviews and meta-analyses than trials on the topic! journals.lww.com/ccmjournal/Cit…
This paper looks at the role of nutrition in bioenergetics WRT critical illness and neurological trauma. ncbi.nlm.nih.gov/pubmed/28004327 Brain= heavily dependent on nutrients for optimal performance, and brain injury=an increase in metabolism and catabolism= caloric and protein deficits.
More developments on investigating bioenergetic failure will include 'lactate kinetics'... #ESICMphysio openarchive.ki.se/xmlui/handle/1… #ESICMphysio
Electrophysiological studies and predicting ominous prognoses has been touted as a viable strategy in ICU.... ccforum.biomedcentral.com/articles/10.11… #ESICMphysio
Final thoughts... 1. Is this important = Yes. There's a lot to unpack over the decades of research. Nothing obvious has come forward as a panacea or major treatment in this area and there's still a lot to study on the mater. #ESICMphysio
2. What can I do clinically? --> Likely involves improving nutritional support to ICU patients and utilising methods to minimise cell stress... this is difficult though with little evidence to support using 'anti-oxidants' - but research is still ongoing! pulmonarychronicles.com/index.php/pulm…
3. It's likely that reduced duration of illness = less cell stress. This is a Captain Obvious statement - but optimisation of ICU treatment may benefit your patient on at a mitochondrial level ;) #ESICMphysio
