In-airway molecular flow sensing: A new technology for continuous, noninvasive monitoring of oxygen consumption in critical care

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Science Advances  10 Aug 2016:
Vol. 2, no. 8, e1600560
DOI: 10.1126/sciadv.1600560
  • Fig. 1 MFS in use during surgery.

    MFS measurement head incorporated in a closed-loop anesthetic delivery system. A 5-m-long pair of cables connects the measurement head to the control unit located away from the operating table.

  • Fig. 2 Partial pressures for the airway gases during an O2 wash-in and wash-out experiment.

    A volunteer was initially asked to breathe laboratory air flowing pass the exhaust side of the MFS through a Y-piece connector. The gas mixture was delivered at approximately 100 liters/min to ensure that no rebreathing of expired gas would take place. After 10 min of stable breathing, the inspired gas was switched from air to medical-grade O2 (>99.5%). Approximately 15 min were allowed for the nitrogen to be fully washed out from the lungs, and then the gas supply was switched back to air. Right panels show expanded versions of the data at times indicated in the main panel to illustrate intrabreath morphology.

  • Fig. 3 Results from direct integration over time to calculate cumulative gas exchange during an O2 wash-in and wash-out experiment.

    Left panel shows the data over the whole time period, and expanded time scales are shown in the two panels to the right. The slopes give the rate of gas uptake (negative in the case of CO2 and H2O). Values are given in ml/min above the shaded regions. Right panels show the scaling of the ordinate axes that have been kept the same to illustrate the relative contributions of each gas species to tidal volume. Note that, apart from the periods of washing N2 out of or into the lung, the overall slope of the N2 volume plot is close to zero, illustrating the precision of the measurements. STPD, standard temperature and pressure, dry.

  • Fig. 4 Gas exchange measurements during repair of an abdominal aortic aneurysm.

    Breathing frequency, airway pressure, tidal volume, oxygen consumption, and carbon dioxide production during elective repair of an abdominal aortic aneurysm. Oxygen consumption and carbon dioxide production are shown breath-by-breath, rather than as the continuous integral of Fig. 3. Events are represented by points as follows: (A) knife to skin; (B) reduction in ventilator driving pressure; (C) aortic clamp applied; (D) fall in blood pressure; (E) metaraminol (fast-acting α-agonist) bolus, and infusion rate increased from 2 to 5 ml/hour; (F) and (G) sequential removal of iliac artery clamps; (H) increase in ventilator driving pressure; and (J) removal of superior retractor restricting rib cage movement.

  • Fig. 5 Design of the MFS measurement head.

    (A) Simplified diagram of the multichannel absorption spectrometer and the pneumotachograph contained within the measurement head. The bidirectional gas path (blue) is shown along with the two mesh screens (gray), across which the pressure drop related to the respiratory flow is measured. Radiation from the 764-nm diode laser (LD 1) used for probing oxygen is injected into an optical cavity constructed from a pair of highly reflective mirrors (red) and collected by a photodiode (PD 1) positioned along the optical axis (green). Two diode lasers, LD 2 and LD 3, located in the drive unit are used to probe for carbon dioxide and water vapor at 2004 and 1368 nm, respectively. Their outputs are spatially combined by a fiber-optic multiplexer located in the drive unit and are transmitted through a hybrid cable into the measurement cell. A fiber-optic collimator launches the radiation into the V path (yellow) and onto the photodiode (PD 2) via a concave mirror. (B) Three-dimensional CAD model of the measurement cell. The differential pressure ports located on the outer sides of the mesh screens are shown, together with the ports for the thermocouple probe and airway pressure sensor.

  • Fig. 6 Characterization of the multichannel laser spectrometer.

    (A to C) Examples of transmission spectra associated with the spectral transitions of oxygen (green), carbon dioxide (red), and water vapor (blue). The spectrum measured by each spectrometric channel (colored symbols) is fitted to a predicted model (black line) by multiple linear regression analysis to retrieve the molecular concentration. The overall acquisition and processing time is within 10 ms. Residuals from the fitted model are shown in the subplots. (D to F) Calibration curves for the three spectrometric channels generated by a constant flow (50 liters/min) of pure gases and various calibration gas mixtures. The experimentally measured gas fractions are shown as symbols, with error bars in the x and y axes representing the absolute uncertainty (±1σ) in the composition of the gravimetrically prepared mixtures and in the output of the gas analyzer, respectively. For most data points, the error bars are contained within the size of the symbols. The line of identity is shown for reference.

  • Table 1 Summary of MFS performance specifications.

    Comparison between MFS performance specifications and the guideline values recommended by the ATS and the ERS (2). NA, not available.

    Volume accuracy±3%±0.2%
    Sample flow<20 ml/min0 ml/min
    Gas analyzer accuracy*±1% FSO for O2±0.45% FSO for O2
    ±1% FSO for CO2±0.5% FSO for CO2
    NA±1.7% FSO for H2O
    Gas analyzer precisionNA for O2±0.18% at 100% O2
    ±0.39% at 21% O2
    NA for CO2±0.20% at 8% CO2
    NA for H2O±1.72% at 4.7% H2O
    Gas analyzer, 10 to 90% rise time<100 ms10 ms
    Data sampling frequency≥100 Hz100 Hz
    Synchronization of flow and gas analysis10 ms5 ms

    *Accuracy is defined as the maximum expected linearity error expressed as a percentage of full-scale output (FSO) range. We have taken the FSO as 0 to 100% for oxygen, 0 to 10% for carbon dioxide, and 0 to 6% for water vapor, with the upper limits chosen as the maximum percentage level of each gas expected in the respired mixture under the experimental conditions.

    †Precision is reported as coefficient of variation (CV), which is defined as the ratio of the SD (σ) to the mean (μ), expressed as a percentage. For each reference mixture, σ and μ are computed from 3 s worth of consecutive concentration values returned every 10 ms. For each channel, precision is reported at the highest concentration point of the calibration curve (see Fig. 2). For oxygen, the value estimated at 21% level is also stated.

    Supplementary Materials

    • Supplementary material for this article is available at

      Supplementary Methods

      Supplementary Results

      fig. S1. Calibration of the pneumotachograph.

      fig. S2. Effect of errors in the pneumotachograph calibration on gas exchange measurements.

      table S1. Summary of spectroscopic parameters.

    • Supplementary Materials

      This PDF file includes:

      • Supplementary Methods
      • Supplementary Results
      • fig. S1. Calibration of the pneumotachograph.
      • fig. S2. Effect of errors in the pneumotachograph calibration on gas exchange measurements.
      • table S1. Summary of spectroscopic parameters.

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