Effect of Thiamine on Oxygen Utilization (VO2) in Critical Illness

Extensive research has been done over the past two decades looking at the role of oxygen
delivery (DO2) and oxygen utilization (VO2) in critical illness. VO2 depends on cardiac
output, arterial oxygen content, and the body's ability to extract oxygen effectively from
the blood. Oxygen demand rises in critical illness as the body goes into a catabolic state,
and lower VO2 has been associated with higher lactate levels and with poorer outcomes.
Although increasing DO2 will often raise VO2, Hayes et al found that a subset of
critically-ill patients failed to demonstrate a rise in VO2 in spite of achieving supranormal
values of cardiac index (CI) and DO2. This group, in contrast to patients whose VO2 rose with
the increase in CI and DO2, had exceedingly poor outcomes, suggesting that an inability to
extract oxygen from the blood confers a poorer prognosis.(1)

Thiamine deficiency can manifest in several ways, but the syndrome of wet beriberi, caused by
thiamine deficiency, includes lactic acidosis, cardiac decompensation and vasodilatory shock,
similar to sepsis and other forms of critical illness. The mechanism by which thiamine
deficiency causes dysfunction rests upon the vitamin's essential role in the Krebs cycle and
Pentose Phosphate Pathway. Lack of adequate thiamine results in the failure of pyruvate to
enter the Krebs Cycle, thus preventing aerobic metabolism. The resulting decrease in aerobic
metabolism and increase in anaerobic metabolism leads to decreased oxygen consumption by the
tissues and increased lactic acid production. The investigators group has found previously
that upwards of 20% of critically ill patients with sepsis are thiamine deficient within 72
hours of presentation. In a dog model of septic shock, Lindenbaum et al have shown that,
regardless of thiamine levels, supplementation with thiamine improved not only lactate
clearance and mean arterial pressure, but increased VO2 as well. The effect of thiamine on
VO2 in critically ill humans has not yet been reported, but an increase in VO2 max after
administration of thiamine to healthy volunteers has been described. VO2 is known to rise in
inflammatory states, reflecting increased energy expenditure. Prior studies have shown that
VO2 will decrease with interventions such as fever control. In spite of VO2 being higher than
normal in critically-ill patients, however, the end-organ damage and lactic acidosis suggest
that it is not high enough to meet the metabolic demands of the critically-ill body. If the
investigators were able to increase VO2 further in critically-ill patients, the investigators
could potentially help maintain aerobic metabolism and decrease tissue hypoxia and the
resulting end-organ damage. The investigators hypothesis is that administering thiamine
intravenously to critically-ill patients will increase VO2.

Multiple methods of measuring VO2 have been used in the ICU, but in the current era where
invasive monitoring with routine use of PA catheters is no longer the norm, indirect
calorimetry became, for a time, the gold standard for measurement of gas exchange in
critically ill, mechanically ventilated patients.(2) The metabolic cart used for indirect
calorimetry is cumbersome and requires frequent calibration to maintain accuracy, however,
and a newer, more portable method has been designed. The Datex-Ohmeda M-COVX device has been
approved for the measurement of VO2 and VCO2 in mechanically ventilated patients. In studies,
it has been validated as a method that is as accurate as indirect calorimetry, and perhaps
even more accurate at higher FiO2.(3,4) The Datex-Ohmeda M-COVX connects to the Carescape
B650 monitor made by GE, and measures VO2 through a single-use spirometer that attaches to
the patient's ventilator tubing. In the following proposal, the investigators present a plan
to examine the effect of thiamine therapy on VO2 in 30 critically-ill, mechanically
ventilated patients, using the Datex-Ohmeda M-COVX module to measure VO2 before and after
thiamine administration.

Inclusion Criteria:

- Adult patients (age > 18 years) admitted to an ICU

- Mechanically ventilated

Exclusion Criteria:

- Unstable ventilator settings during measurement of VO2

- Temp > 100 at time of VO2 measurement

- FIO2 > 60%

- Endotracheal cuff leak, chest tube, or other evident source of air leak

- Thiamine supplementation within 24 hours prior to study enrollment