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

NCT ID: NCT01462279

Last Updated: 2018-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-10-31

Brief Summary

The objective of this study is to determine the effect of thiamine therapy on oxygen consumption in critically-ill patients. The investigators will evaluate this by measuring VO2 before and after thiamine administration in patients admitted to the ICU and requiring mechanical ventilation.

Detailed Description

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.

Conditions

Acute Respiratory Failure

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Thiamine

Open label - 200mg IV

Group Type: EXPERIMENTAL

Thiamine

Intervention Type: DRUG

200mg of intravenous thiamine in 50ml of D5W will be infused over 30 minutes once

Interventions

Thiamine

200mg of intravenous thiamine in 50ml of D5W will be infused over 30 minutes once

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Medical Association

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Michael Donnino

Associate Professor of Emergency Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Katherine M Berg, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Michael W Donnino, MD

Role: PRINCIPAL_INVESTIGATOR

Beth Israel Deaconess Medical Center

Locations

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, United States

Countries

United States

References

Berg KM, Gautam S, Salciccioli JD, Giberson T, Saindon B, Donnino MW. Intravenous thiamine is associated with increased oxygen consumption in critically ill patients with preserved cardiac index. Ann Am Thorac Soc. 2014 Dec;11(10):1597-601. doi: 10.1513/AnnalsATS.201406-259BC.

Reference Type: DERIVED

PMID: 25390455 (View on PubMed)

Other Identifiers

2010P000312

Identifier Type: -

Identifier Source: org_study_id