Gas Kinetics and Metabolism in Anesthesia During Non Steady State

During clinical anesthesia, it is astonishing that CO2 monitoring consists mainly of
end-tidal PCO2 to confirm endotracheal intubation and to estimate ventilation, and O2
monitoring consists of a single PO2 measurement to detect a hypoxic gas mixture. Better
understanding of how O2 and CO2 kinetics monitoring can define systems pathophysiology will
greatly enhance safety in anesthesia by detecting critical events such as abrupt decrease in
cardiac output (Q.T) by vena-caval compression during abdominal surgery, occurrence of CO2
pulmonary embolism during laparoscopy, rising tissue O2 consumption (V.O2) during light
anesthesia, and onset of anaerobic metabolism (V.CO2 is disproportionately higher than
V.O2).

In the previous grant period, discoveries of CO2 kinetics during non-steady state revealed
significant gaps in understanding of O2 kinetics. To this end, a 5-compartment lung model of
gas kinetics in the body during non-steady state has been developed, that incorporates
complex interactions between O2 and CO2 in the lung, blood, and tissues. This computer model
was used to formulate the following hypotheses, and will elucidate mechanisms underlying the
subsequent measured data in anesthetized patients.

The investigators have already developed two innovative devices that are essential for the
V.O2 measurement: A fast response temperature and humidity sensor, and a mixing device (a
bymixer) for the measurement of mixed gas fraction, especially designed for anesthesia
systems. The investigators have also designed a sophisticated bench system for the
validation of both devices, which showed the high accuracy and performance of our
measurements.

Hypotheses that will be tested in our overall research theme include:

- That pulmonary O2 uptake (V.O2) in anesthetized patients is much lower than the value
quoted in the literature.

- That inhalation anesthesia influences V.O2 differently than total intravenous
anesthesia (TIVA).

- That an acute decrease in cardiac output (Q.T) (by patient position change) will
transiently decrease V.O2 but the decrease in CO2 elimination (V.CO2) is sustained
because tissue CO2 stores are a hundred fold greater than O2 (please see previously
approved IRB protocol, HS# 2000-1325).

- That positive end-expiratory pressure (PEEP) decreases V.O2 and V.CO2 due to decreases
in Q.T and alveolar ventilation (V.A), and appearance of high ventilation-to-perfusion
(V.A/Q.) units (please see previously approved IRB protocol, HS# 2000-1325).

- That Trendelenburg (head down) position increases V.O2 and V.CO2 due to increase in
Q.T.

- That V.O2 can help to determine the necessity of blood transfusion.

- That the continuous measurement of the respiratory quotient (RQ=V.CO2/V.O2) can detect
transition to anaerobic metabolism.

- That the continuous measurement of the respiratory RQ can be a good alternative to
arterial blood gas sampling.

- That the continuous measurement of the respiratory RQ can determine the necessity of
nutritional support during long operations.

In this protocol, the investigators will study the clinical implications of these
measurements, believing that they are the missing links in anesthesia monitoring.
Elucidating the mechanisms underlying this acute pathophysiology will advance the
understanding of O2 and CO2 kinetics during non-steady state, and allow the non-invasive
diagnosis of critical events during clinical anesthesia conferring increased safety,
especially for the majority of healthy patients who receive only non-invasive monitoring.

A separate section of the study, which compliments the metabolic gas exchange study with the
bymixer flow system is the examination of respiratory gas with a portable mass-spectrometer
to detect volatile organic compounds during anaerobic metabolism. The experimental anaerobic
model is adult patients undergoing a surgery that requires tourniquet. Anaerobic metabolism
will be detected by acid base balance blood test, the bymixer flow measurement and the mass
spectrometer. Anesthesia will be maintained by total intravenous anesthesia (TIVA) and each
patient will have an arterial line. No other intervention would be taken. It is an
observational type study.

Inclusion Criteria:

- All adult patients at UCIMC who are undergoing anesthesia and surgery are eligible
for the studies

- Patients must be American Society of Anesthesiologists (ASA) Class 1 or 2 (generally
healthy patients). We plan on studying 100 patients, divided into 5 equally numbered
groups. A power analysis of the sample size shows the need for minimum of 20
patients. High risk 3 subgroups (ASA 3), approximately 20 adult patients (included
within the 100 planned patients), will be investigated for the (1) RQ correlation
with arterial blood gas, (2) for the exercise study and (3) for the esophageal
Doppler studies. These study groups include patients that are categorized as ASA 1, 2
or 3, (total of 60 patients) however; the total number of ASA 3 patients will not
exceed 20. Subjects having surgeries around the head and neck, as well as surgeries
that require the patient to lie face down will be excluded from the study

- Gender and minority status will not be an exclusion factor for any potential study
patient

Exclusion Criteria:

Cardiovascular:

- Significant vascular disease, especially cardiac and cerebral vascular disease

- Patients will be excluded if they have a history of having a myocardial infarction or
cerebral vascular attack

- Significant hypertension (> 170 systolic, > 90 diastolic) (except for the high risk
subgroup mentioned before)

Pulmonary:

- Significant asthma (mild persistent or greater according to the National Asthma
Education and Prevention Program classification system) chronic obstructive pulmonary
disease (COPD) (Stage II: Moderate COPD according to the Global Initiative for
Chronic Obstructive Lung Disease classification

- Worsening airflow limitation, (FEV1 ≤30% ), and usually the progression of symptoms,
with shortness of breath typically developing on exertion), bullous lung disease, or
raised intra-cranial pressure (except for the high risk subgroup mentioned before)

Esophageal Doppler:

- If localized pathology is present, including pharyngeal tumor or significant
esophageal varices, then the esophageal probe will not be used.

Emergency cases:

- Excluded from the study. Only elective patients will be enrolled.

Short surgeries:

- Surgeries that are expected to last 45 minutes or less will be excluded.