Oxidation-reduction potential in relation to vitamin C status in criticall ill patients

Intravenous vitamin C may improve the outcome of critically ill patients by
attacking the overwhelming oxidative stress which contributes to organ damage.
Critically illness-induced oxidative stress decreases plasma vitamin C levels
due to increased metabolic consumption in combination with reduced recycling of
dehydroascorbic acid (oxidized vitamin C) while intake is reduced. Acute
deficiency is the result.Up to now, there is no fast, reliable test to quantify
either oxidative stress or measure vitamin C levels. Oxidative stress is mainly
assessed by indirect biochemical parameters, utilizing assays assessing damage
to lipids, proteins and DNA.Their measurement is difficult, time-consuming and
unfeasible in clinical practice.Similarly, proper determination of vitamin C
levels requires an HPLC setting and is complex, laborious, costly and not
available for daily practice. Recently, a novel technology has been developed,
allowing point-of-care measurement of the oxidation-reduction potential (ORP)
and anti-oxidant capacity. ORP (also called the redox potential) is the net
balance in activity between oxidants and reductants. ORP could be a useful tool
in clinical practice as well to estimate the degree of oxidative stress. We
performed a pilot study to determine whether sORP and AOC could be useful to
estimate vitamin C status in critically ill patients. High sORP and low AOC
showed a good correlation with low vitamin C plasma levels.

Therefore, our hypothesis is that low vitamin C levels are related to severity
of oxidative stress, represented by high sORP and low AOC levels. As a result,
measurement of sORP and AOC could potentially identify critically ill patients
who are vitamin C deficient and are most likely to benefit from i.v. vitamin C
administration. This will be investigated in a multicenter randomised
controlled trial comparing 3 grams and 10 grams vitamin C with placebo.
However, it is important to investigate the different correlations between
vitamin C plasma levels, ORP and AOC at different laboratory processing
conditions in this validation study first (see page 13 and 14 of the protocol).
After this validation study, the most reliable way of processing the samples
can be chosen for implementation during the mentioned RCT which will enhance
its results. Furthermore, the validation of the RedoxSYS system will contribute
to its value as point-of-care measurement.

To investigate and validate the relation between vitamin C levels and severity
of oxidative stress, represented by sORP and AOC levels at different laboratory
processing conditions. Furthermore, to determine the relation between sORP,
AOC, vitamin C plasma concentrations and clinical outcome measures.

Single center, prospective, observational study

The study is a validation of a new point-of-care device and offers no risk for
the patient. The blood will be sampled from an arterial line, which is
routinely present in critically ill patient for monitoring blood pressure and
blood sampling. A puncture is not necessary and the patient will not even
notice the blood sampling. Clinical characteristics and outcomes of the study
are variables which are routinely registered in the patient data management
system of the unit. The included patients will not benefit from the study.
There may however be benefit for future patients. We will include patients in
which oxidative stress plays a major role (e.g. sepsis, trauma or
ischemia/reperfusion injury) and thus are most likely to have vitamin C
deficiency and benefit from high-dose intravenous (i.v.) vitamin C. A baseline
value (at day 1) is highly important and contributes to the decision making
regarding the timing of vitamin C administration. In addition, we will perform
measurements at day 3 as well because a previous study showed that vitamin C
concentrations decreased during the first 3 days of ICU-admission.