Noninvasive Assessment of Impaired Gas Exchange with the Alveolar Gas Monitor Predicts Clinical Deterioration in COVID-19 Patients.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic magnified the importance of gas exchange abnormalities in early respiratory failure. Pulse oximetry (SpO2) has not been universally effective for clinical decision-making, possibly because of limitations. The alveolar gas monitor (AGM100) adds exhaled gas tensions to SpO2 to calculate the oxygen deficit (OD). The OD parallels the alveolar-to-arterial oxygen difference (AaDO2) in outpatients with cardiopulmonary disease. We hypothesized that the OD would discriminate between COVID-19 patients who require hospital admission and those who are discharged home, as well as predict need for supplemental oxygen during the index hospitalization. METHODS: Patients presenting with dyspnea and COVID-19 were enrolled with informed consent and had OD measured using the AGM100. The OD was then compared between admitted and discharged patients and between patients who required supplemental oxygen and those who did not. The OD was also compared to SpO2 for each of these outcomes using receiver operating characteristic (ROC) curves. RESULTS: Thirty patients were COVID-19 positive and had complete AGM100 data. The mean OD was significantly (p = 0.025) higher among those admitted 50.0 ± 20.6 (mean ± SD) vs. discharged 27.0 ± 14.3 (mean ± SD). The OD was also significantly (p < 0.0001) higher among those requiring supplemental oxygen 60.1 ± 12.9 (mean ± SD) vs. those remaining on room air 25.2 ± 11.9 (mean ± SD). ROC curves for the OD demonstrated very good and excellent sensitivity for predicting hospital admission and supplemental oxygen administration, respectively. The OD performed better than an SpO2 threshold of <94%. CONCLUSIONS: The AGM100 is a novel, noninvasive way of measuring impaired gas exchange for clinically important endpoints in COVID-19.

Development and Validation of an ICU Delirium Playbook for Provider Education.

Although delirium detection and prevention practices are recommended in critical care guidelines, there remains a persistent lack of effective delirium education for ICU providers. To address this knowledge-practice gap, we developed an "ICU Delirium Playbook" to educate providers on delirium detection (using the Confusion Assessment Method for the ICU) and prevention. DESIGN: Building on our previous ICU Delirium Video Series, our interdisciplinary team developed a corresponding quiz to form a digital "ICU Delirium Playbook." Playbook content validity was evaluated by delirium experts, and face validity by an ICU nurse focus group. Additionally, focus group participants completed the quiz before and after video viewing. Remaining focus group concerns were evaluated in semi-structured follow-up interviews. SETTING: Online validation survey, virtual focus group, and virtual interviews. SUBJECTS: The validation group included six delirium experts in the fields of critical care, geriatrics, nursing, and ICU education. The face validation group included nine ICU nurses, three of whom participated in the semi-structured feedback interviews. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The 44-question quiz had excellent content validity (average scale-level content validity index [S-CVI] of individual items = 0.99, universal agreement S-CVI = 0.93, agreement κ ≥ 0.75, and clarity p ≥ 0.8). The focus group participants completed the Playbook in an average (sd) time of 53 (14) minutes, demonstrating significant improvements in pre-post quiz scores (74% vs 86%; p = 0.0009). Verbal feedback highlighted the conciseness, utility, and relevance of the Playbook, with all participants agreeing to deploy the digital education module in their ICUs. CONCLUSIONS: The ICU Delirium Playbook is a novel, first-of-its-kind asynchronous digital education tool aimed to standardize delirium detection and prevention practices. After a rigorous content and face validation process, the Playbook is now available for widespread use.

Nitrogen-based lung clearance index: a valid physiological biomarker for the clinic.

Multiple breath washout (MBW) testing is increasingly used as a physiological measurement in the clinic, due in part to the availability of commercial equipment and reference values for MBW indices. Commercial N2 washout devices are usually based on indirect measurement of N2 concentration (CN2), by directly measuring either molar mass and O2 and CO2, or molar mass and CO2. We aim to elucidate the role of two potential pitfalls associated with N2-MBW testing that could override its physiological content: indirect N2 measurement and blood-solubility of N2. We performed MBW in 12 healthy adult subjects using a commercial device (MBWindirect) with simultaneous direct gas concentration measurements by mass spectrometry (MBWdirect) and compared CN2 between MBWdirect and MBWindirect. We also measured argon concentration during the same washouts to verify the maximal effect gas solubility can have on N2-based functional residual capacity (FRC) and lung clearance index (LCI). Continuous N2 concentration traces were very similar for MBWindirect and MBWdirect, resulting in comparable breath-by-breath washout plots of expired concentration and in no significant differences in FRCN2, LCIN2, Scond, and Sacin between the two methods. Argon washouts were slightly slower than N2 washouts, as expected for a less diffusive and more soluble gas. Finally, comparison between LCIN2 and LCIAr indicates that the maximum impact from blood-tissue represents less than half a LCI unit in normal subjects. In conclusion, we have demonstrated by direct measurement of N2 and twice as soluble argon, that indirect N2 measurement can be safely used as a meaningful physiological measurement.NEW & NOTEWORTHY The physiological content of N2 multibreath washout testing has been questioned due to N2 indirect measurement accuracy and N2 blood solubility. With direct measurement of N2 and twice as soluble argon, we show that these effects are largely outweighed by ease of use.

Noninvasive measurement of pulmonary gas exchange: comparison with data from arterial blood gases.

A new noninvasive method was used to measure the impairment of pulmonary gas exchange in 34 patients with lung disease, and the results were compared with the traditional ideal alveolar-arterial Po2 difference (AaDO2) calculated from arterial blood gases. The end-tidal Po2 was measured from the expired gas during steady-state breathing, the arterial Po2 was derived from a pulse oximeter if the SpO2 was 95% or less, which was the case for 23 patients. The difference between the end-tidal and the calculated Po2 was defined as the oxygen deficit. Oxygen deficit was 42.7 mmHg (SE 4.0) in this group of patients, much higher than the means previously found in 20 young normal subjects measured under hypoxic conditions (2.0 mmHg, SE 0.8) and 11 older normal subjects (7.5 mmHg, SE 1.6) and emphasizes the sensitivity of the new method for detecting the presence of abnormal gas exchange. The oxygen deficit was correlated with AaDO2 ( R2 0.72). The arterial Po2 that was calculated from the noninvasive technique was correlated with the results from the arterial blood gases ( R2 0.76) and with a mean bias of +2.7 mmHg. The Pco2 was correlated with the results from the arterial blood gases (R2 0.67) with a mean bias of -3.6 mmHg. We conclude that the oxygen deficit as obtained from the noninvasive method is a very sensitive indicator of impaired pulmonary gas exchange. It has the advantage that it can be obtained within a few minutes by having the patient simply breathe through a tube.

A New, Noninvasive Method of Measuring Impaired Pulmonary Gas Exchange in Lung Disease: An Outpatient Study.

BACKGROUND: It would be valuable to have a noninvasive method of measuring impaired pulmonary gas exchange in patients with lung disease and thus reduce the need for repeated arterial punctures. This study reports the results of using a new test in a group of outpatients attending a pulmonary clinic. METHODS: Inspired and expired partial pressure of oxygen (PO2) and Pco2 are continually measured by small, rapidly responding analyzers. The arterial PO2 is calculated from the oximeter blood oxygen saturation level and the oxygen dissociation curve. The PO2 difference between the end-tidal gas and the calculated arterial value is called the oxygen deficit. RESULTS: Studies on 17 patients with a variety of pulmonary diseases are reported. The mean ± SE oxygen deficit was 48.7 ± 3.1 mm Hg. This finding can be contrasted with a mean oxygen deficit of 4.0 ± 0.88 mm Hg in a group of 31 normal subjects who were previously studied (P < .0001). The analysis emphasizes the value of measuring the composition of alveolar gas in determining ventilation-perfusion ratio inequality. This factor is largely ignored in the classic index of impaired pulmonary gas exchange using the ideal alveolar PO2 to calculate the alveolar-arterial oxygen gradient. CONCLUSIONS: The results previously reported in normal subjects and the present studies suggest that this new noninvasive test will be valuable in assessing abnormal gas exchange in the clinical setting.

Carbon Dioxide Exposure Resulting From Hood Protective Equipment Used in Joint Arthroplasty Surgery.

BACKGROUND: To protect both the surgeon and patient during procedures, hooded protection shields are used during joint arthroplasty procedures. Headache, malaise, and dizziness, consistent with increased carbon dioxide (CO2) exposure, have been anecdotally reported by surgeons using hoods. We hypothesized that increased CO2 concentrations were causing reported symptoms. METHODS: Six healthy subjects (4 men) donned hooded protection, fan at the highest setting. Arm cycle ergometry at workloads of 12 and 25 watts (W) simulated workloads encountered during arthroplasty. Inspired O2 and CO2 concentrations at the nares were continuously measured at rest, 12 W, and 25 W. At each activity level, the fan was deactivated and the times for CO2 to reach 0.5% and 1.0% were measured. RESULTS: At rest, inspired CO2 was 0.14% ± 0.04%. Exercise had significant effect on CO2 compared with rest (0.26% ± 0.08% at 12 W, P = .04; 0.31% ± 0.05% at 25 W, P = .003). Inspired CO2 concentration increased rapidly with fan deactivation, with the time for CO2 to increase to 0.5% and 1.0% after fan deactivation being rapid but variable (0.5%, 12 ± 9 seconds; 1%, 26 ± 15 seconds). Time for CO2 to return below 0.5% after fan reactivation was 20 ± 37 seconds. CONCLUSION: During simulated joint arthroplasty, CO2 remained within Occupational Safety and Health Administration (OSHA) standards with the fan at the highest setting. With fan deactivation, CO2 concentration rapidly exceeds OSHA standards.

Total and regional deposition of inhaled aerosols in supine healthy subjects and subjects with mild-to-moderate COPD.

Despite substantial development of sophisticated subject-specific computational models of aerosol transport and deposition in human lungs, experimental validation of predictions from these new models is sparse. We collected aerosol retention and exhalation profiles in seven healthy volunteers and six subjects with mild-to-moderate COPD (FEV1 = 50-80%predicted) in the supine posture. Total deposition was measured during continuous breathing of 1 and 2.9 µm-diameter particles (tidal volume of 1 L, flow rate of 0.3 L/s and 0.75 L/s). Bolus inhalations of 1 µm particles were performed to penetration volumes of 200, 500 and 800 mL (flow rate of 0.5 L/s). Aerosol bolus dispersion (H), deposition, and mode shift (MS) were calculated from these data. There was no significant difference in total deposition between healthy subjects and those with COPD. Total deposition increased with increasing particle size and also with increasing flow rate. Similarly, there was no significant difference in aerosol bolus deposition between subject groups. Yet, the rate of increase in dispersion and of decrease in MS with increasing penetration volume was higher in subjects with COPD than in healthy volunteers (H: 0.798 ± 0.205 vs. 0.527 ± 0.122 mL/mL, p=0.01; MS: -0.271±0.129 vs. -0.145 ± 0.076 mL/mL, p=0.05) indicating larger ventilation inhomogeneities (based on H) and increased flow sequencing (based on MS) in the COPD than in the healthy group. In conclusion, in the supine posture, deposition appears to lack sensitivity for assessing the effect of lung morphology and/or ventilation distribution alteration induced by mild-to-moderate lung disease on the fate of inhaled aerosols. However, other parameters such as aerosol bolus dispersion and mode shift may be more sensitive parameters for evaluating models of lungs with moderate disease.

Lung function is unchanged in the 1 G environment following 6-months exposure to microgravity.

Many organ systems adapt in response to the removal of gravity, such as that occurring during spaceflight. Such adaptation occurs over varying time periods depending on the organ system being considered, but the effect is that upon a return to the normal 1 G environment, the organ system is ill-adapted to that environment. As a consequence, either countermeasures to the adaptive process in flight, or rehabilitation upon return to 1 G is required. To determine whether the lung changed in response to a long period without gravity, we studied numerous aspects of lung function on ten subjects (one female) before and after they were exposed to 4-6 months of microgravity (microG, weightlessness) in the normobaric normoxic environment of the International Space Station. With the exception of small (and likely physiologically inconsequential) changes in expiratory reserve volume, one index of peripheral gas mixing in the periphery of the lung, and a possible slight reduction in D(L)CO in the early postflight period despite an unchanged cardiac output, lung function was unaltered by 4-6 months in microG. These results suggest that unlike many other organ systems in the human body, lung function returns to normal after long term exposure to the removal of gravity. We conclude that that in a normoxic, normobaric environment, lung function is not a concern following long-duration future spaceflight exploration missions of up to 6 months.

Vital capacity, respiratory muscle strength, and pulmonary gas exchange during long-duration exposure to microgravity.

Extended exposure to microgravity (microG) is known to reduce strength in weight-bearing muscles and was also reported to reduce respiratory muscle strength. Short- duration exposure to microG reduces vital capacity (VC), a surrogate measure for respiratory muscle strength, for the first few days, with little change in O2 uptake, ventilation, or end-tidal partial pressures. Accordingly we measured VC, maximum inspiratory and expiratory pressures, and indexes of pulmonary gas exchange in 10 normal subjects (9 men, 1 woman, 39-52 yr) who lived on the International Space Station for 130-196 days in a normoxic, normobaric atmosphere. Subjects were studied four times in the standing and supine postures preflight at sea level at 1 G, approximately monthly in microG, and multiple times postflight. VC in microG was essentially unchanged compared with preflight standing [5.28 +/- 0.08 liters (mean +/- SE), n = 187; 5.24 +/- 0.09, n = 117, respectively; P = 0.03] and considerably greater than that measured supine in 1G (4.96 +/- 0.10, n = 114, P < 0.001). There was a trend for VC to decrease after the first 2 mo of microG, but there were no changes postflight. Maximum respiratory pressures in microG were generally intermediate to those standing and supine in 1G, and importantly they showed no decrease with time spent in microG. O2 uptake and CO2 production were reduced (approximately 12%) in extended microG, but inhomogeneity in the lung was not different compared with short-duration exposure to microG. The results show that VC is essentially unchanged and respiratory muscle strength is maintained during extended exposure to microG, and metabolic rate is reduced.

Pulmonary gas exchange is not impaired 24 h after extravehicular activity.

Extravehicular activity (EVA) during spaceflight involves a significant decompression stress. Previous studies have shown an increase in the inhomogeneity of ventilation-perfusion ratio (VA/Q) after some underwater dives, presumably through the embolic effects of venous gas microemboli in the lung. Ground-based chamber studies simulating EVA have shown that venous gas microemboli occur in a large percentage of the subjects undergoing decompression, despite the use of prebreathe protocols to reduce dissolved N(2) in the tissues. We studied eight crewmembers (7 male, 1 female) of the International Space Station who performed 15 EVAs (initial cabin pressure 748 mmHg, final suit pressure either approximately 295 or approximately 220 mmHg depending on the suit used) and who followed the denitrogenation procedures approved for EVA from the International Space Station. The intrabreath VA/Q slope was calculated from the alveolar Po(2) and Pco(2) in a prolonged exhalation maneuver on the day after EVA and compared with measurements made in microgravity on days well separated from the EVA. There were no significant changes in intrabreath VA/Q slope as a result of EVA, although there was a slight increase in metabolic rate and ventilation (approximately 9%) on the day after EVA. Vital capacity and other measures of pulmonary function were largely unaltered by EVA. Because measurements could only be performed on the day after EVA because of logistical constraints, we were unable to determine an acute effect of EVA on VA/Q inequality. The results suggest that current denitrogenation protocols do not result in any major lasting alteration to gas exchange in the lung.

Effect of 6 degrees head-down tilt on cardiopulmonary function: comparison with microgravity.

BACKGROUND: Head-down tilt (HDT) of 6 degrees is a commonly used model of weightlessness, but there are few comparisons with actual microgravity. HYPOTHESIS: Our study was designed to prove that the changes in cardiopulmonary function seen in HDT would be similar to those seen in microgravity. METHODS: We compared measurements of cardiovascular and pulmonary function from three separate spaceflights of 14 to 17 d duration, with data collected during a 17-d period of HDT. RESULTS: HDT proved a good model of the cardiovascular response to microgravity, resulting in increases in cardiac output and stroke volume of a similar magnitude to those seen in microgravity, with a concomitant reduction in heart rate. By contrast, HDT was a poor model of the effects of microgravity on pulmonary ventilation and gas exchange. CONCLUSION: Pulmonary function in HDT approximated the changes seen in the 1-G supine posture, while in microgravity this was much closer to that seen in the 1-G upright position. The differences probably reflect the fact that changes in cardiovascular function result primarily from fluid shifts within the entire body, whereas changes in pulmonary ventilation are primarily a result of mechanical influences on the lung and chest and abdominal wall.