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).

Study Overview

• Status: Withdrawn
• Conditions: Anesthetized Healthy Patients (ASA 1 or 2) in the Supine Position, Excluding Head, Neck and Head Surgeries; Anesthetized Patient With Severe Systemic Disease (ASA 3 or 4)
• Intervention / Treatment: Device: connection of measuring device to anesthesia circuit; Procedure: placement of esophageal Doppler for cardiac output measurements; Device: Humidity sensor; Device: A mixing chamber (bymixer); Device: Pneumotachometer cuvette; Procedure: drawing of blood sample through an arterial line, placed according to clinical criteria by primary anesthesia team; Device: Mass spectrometer sampling port; Procedure: adding PEEP during anesthesia; Procedure: changing operating room bed position (head down and up position)

Detailed Description

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Adult patients in the supine position excluding surgeries around the head and neck area

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
metabolic gas exchange and cardiac output	Device: connection of measuring device to anesthesia circuit; same as name; Procedure: placement of esophageal Doppler for cardiac output measurements; same; Device: Humidity sensor; Small conventional anesthesia T piece including tiny 2 thermometer inside; Device: A mixing chamber (bymixer); 2 mixing chambers (bymixers) composed of 2 arms where one arm serves as a mixing (passive) arm for the measurement of mixed gas fraction. The bymixer is made of conventional anesthesia supplies and does not influence dead space nor circuit resistance.; Device: Pneumotachometer cuvette; The pneumotachometer cuvette is used by many anesthesia monitors to measure gas flow.
mass spectrometer and anaerobic metabolism	Device: connection of measuring device to anesthesia circuit; same as name; Device: Humidity sensor; Small conventional anesthesia T piece including tiny 2 thermometer inside; Device: A mixing chamber (bymixer); 2 mixing chambers (bymixers) composed of 2 arms where one arm serves as a mixing (passive) arm for the measurement of mixed gas fraction. The bymixer is made of conventional anesthesia supplies and does not influence dead space nor circuit resistance.; Device: Pneumotachometer cuvette; The pneumotachometer cuvette is used by many anesthesia monitors to measure gas flow.; Procedure: drawing of blood sample through an arterial line, placed according to clinical criteria by primary anesthesia team; same; Device: Mass spectrometer sampling port; Designed for the anesthesia tubing and connected at the airway opening. it has small volume (3 mL) and do not influence circuit resistance.; Other Names: V&F Instruments, Airsense (www.vandf.com)
metaboic gas exchange and type of anesthesia induction	Device: connection of measuring device to anesthesia circuit; same as name; Device: Humidity sensor; Small conventional anesthesia T piece including tiny 2 thermometer inside; Device: A mixing chamber (bymixer); 2 mixing chambers (bymixers) composed of 2 arms where one arm serves as a mixing (passive) arm for the measurement of mixed gas fraction. The bymixer is made of conventional anesthesia supplies and does not influence dead space nor circuit resistance.; Device: Pneumotachometer cuvette; The pneumotachometer cuvette is used by many anesthesia monitors to measure gas flow.
metabolic gas exchange and PEEP	Device: connection of measuring device to anesthesia circuit; same as name; Device: Humidity sensor; Small conventional anesthesia T piece including tiny 2 thermometer inside; Device: A mixing chamber (bymixer); 2 mixing chambers (bymixers) composed of 2 arms where one arm serves as a mixing (passive) arm for the measurement of mixed gas fraction. The bymixer is made of conventional anesthesia supplies and does not influence dead space nor circuit resistance.; Device: Pneumotachometer cuvette; The pneumotachometer cuvette is used by many anesthesia monitors to measure gas flow.; Procedure: adding PEEP during anesthesia; same
metabolic gas exchange and trendelenburg position	Device: connection of measuring device to anesthesia circuit; same as name; Device: Humidity sensor; Small conventional anesthesia T piece including tiny 2 thermometer inside; Device: A mixing chamber (bymixer); 2 mixing chambers (bymixers) composed of 2 arms where one arm serves as a mixing (passive) arm for the measurement of mixed gas fraction. The bymixer is made of conventional anesthesia supplies and does not influence dead space nor circuit resistance.; Device: Pneumotachometer cuvette; The pneumotachometer cuvette is used by many anesthesia monitors to measure gas flow.; Procedure: changing operating room bed position (head down and up position); same
Patients requiring tourniquet during surgery; Patients undergoing orthopaedic surgeries requiring tourniquet intervention. Oxygen consumption and CO2 production were measured before, during and after tourniquet release.
Patients prone to metabolic acidosis; Oxygen consumption and CO2 measurements taken during long surgeries prone to metabolic acidosis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Correlation between VO2 to type of anesthesia maintenance	45 minutes
Correlation between acid base balance and indirect calorimetry	2 hours
Detection of volatile organic compound during anaerobic metabolism	3 hours
Influence of anesthesia induction on metabolic gas exchange	45 minutes

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Investigators: Principal Investigator: Peter H Breen, MD, FRCPC, UCI Medical Center; Study Director: Abraham Rosenbaum, MD, UCI Medical Center

Publications and helpful links

General Publications

• Rosenbaum A, Kirby C, Breen PH. Measurement of oxygen uptake and carbon dioxide elimination using the bymixer: validation in a metabolic lung simulator. Anesthesiology. 2004 Jun;100(6):1427-37. doi: 10.1097/00000542-200406000-00015.
• Rosenbaum A, Breen PH. Novel, adjustable, clinical bymixer measures mixed expired gas concentrations in anesthesia circle circuit. Anesth Analg. 2003 Nov;97(5):1414-1420. doi: 10.1213/01.ANE.0000083420.15268.3A.
• Breen PH, Isserles SA, Taitelman UZ. Non-steady state monitoring by respiratory gas exchange. J Clin Monit Comput. 2000;16(5-6):351-60. doi: 10.1023/a:1011447500984.
• Breen PH. Importance of temperature and humidity in the measurement of pulmonary oxygen uptake per breath during anesthesia. Ann Biomed Eng. 2000 Sep;28(9):1159-64. doi: 10.1114/1.1312184.
• Breen PH, Serina ER. Bymixer provides on-line calibration of measurement of CO2 volume exhaled per breath. Ann Biomed Eng. 1997 Jan-Feb;25(1):164-71. doi: 10.1007/BF02738547.
• Breen PH, Serina ER, Barker SJ. Measurement of pulmonary CO2 elimination must exclude inspired CO2 measured at the capnometer sampling site. J Clin Monit. 1996 May;12(3):231-6. doi: 10.1007/BF00857644.
• Breen PH, Mazumdar B, Skinner SC. Capnometer transport delay: measurement and clinical implications. Anesth Analg. 1994 Mar;78(3):584-6. doi: 10.1213/00000539-199403000-00027.
• Breen PH, Isserles SA, Harrison BA, Roizen MF. Simple computer measurement of pulmonary VCO2 per breath. J Appl Physiol (1985). 1992 May;72(5):2029-35. doi: 10.1152/jappl.1992.72.5.2029.
• Isserles SA, Breen PH. Can changes in end-tidal PCO2 measure changes in cardiac output? Anesth Analg. 1991 Dec;73(6):808-14. doi: 10.1213/00000539-199112000-00023.
• Rosenbaum A, Breen PH. Importance and interpretation of fast-response airway hygrometry during ventilation of anesthetized patients. J Clin Monit Comput. 2007 Jun;21(3):137-46. doi: 10.1007/s10877-006-9065-5. Epub 2007 Mar 16.
• Rosenbaum A, Kirby C, Breen PH. New metabolic lung simulator: development, description, and validation. J Clin Monit Comput. 2007 Apr;21(2):71-82. doi: 10.1007/s10877-006-9058-4. Epub 2007 Mar 1.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2005
• Primary Completion (Actual): January 13, 2012
• Study Completion (Actual): January 13, 2012

Study Registration Dates

• First Submitted: September 21, 2005
• First Submitted That Met QC Criteria: September 21, 2005
• First Posted (Estimate): September 23, 2005

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: March 19, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Oxygen consumption; Indirect calorimetry; CO2 production; Non steady state; Anesthesia monitoring; Critical events during anesthesia; Acid base balance; Metabolism during anesthesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: R01 HL 42637 [HS# 2005-4256]; (UCI IRB ID)2005-4256 (Other Identifier: UC Irvine Institutional Review Board)