Multiple Inert Gas Elimination Technique Research Articles

Ultra-low tidal volume ventilation during cardiopulmonary resuscitation shows no mitigating effect on pulmonary end-organ damage compared to standard ventilation: insights from a porcine model

ObjectiveThis study aimed to determine whether ultra-low tidal volume ventilation (ULTVV) applied during cardiopulmonary resuscitation (CPR) compared with standard ventilation (intermittent positive pressure ventilation, IPPV) can reduce pulmonary end-organ damage in the post-resuscitation period.MethodsA prospective, randomized trial was conducted using a porcine model (n = 45). The animals were divided into three groups: IPPV, ULTVV, and a sham control group. Juvenile male pigs underwent CPR after inducing ventricular fibrillation and received the designated ventilation intervention [IPPV: tidal volume 6–8 ml per kilogram body weight (ml/kg BW), respiratory rate 10/min, FiO2 1.0; ULTVV: tidal volume 2–3 ml/kg BW, respiratory rate 50/min, FiO2 1.0]. A 20-h observation period followed if return of spontaneous circulation was achieved. Histopathological examination using the diffuse alveolar damage scoring system was performed on postmortem lung tissue samples. Arterial and venous blood gas analyses and ventilation/perfusion measurements via multiple inert gas elimination technique (MIGET) were repeatedly recorded during the experiment.ResultsOut of the 45 experiments conducted, 28 animals were excluded based on predefined criteria. Histopathological analysis showed no significant differences in lung damage between the ULTVV and IPPV groups. ULTVV demonstrated adequate oxygenation and decarboxylation. MIGET measurements during and after resuscitation revealed no significant differences between the intervention groups.ConclusionIn the short-term follow-up phase, ULTVV demonstrated similar histopathological changes and functional pulmonary parameters compared to standard ventilation. Further research is needed to investigate the long-term effects and clinical implications of ULTVV in resuscitation settings.

Causes of Hypoxemia in COVID-19 Acute Respiratory Distress Syndrome: A Combined Multiple Inert Gas Elimination Technique and Dual-energy Computed Tomography Study.

Despite the fervent scientific effort, a state-of-the art assessment of the different causes of hypoxemia (shunt, ventilation-perfusion mismatch, and diffusion limitation) in COVID-19 acute respiratory distress syndrome (ARDS) is currently lacking. In this study, the authors hypothesized a multifactorial genesis of hypoxemia and aimed to measure the relative contribution of each of the different mechanism and their relationship with the distribution of tissue and blood within the lung. In this cross-sectional study, the authors prospectively enrolled 10 patients with COVID-19 ARDS who had been intubated for less than 7 days. The multiple inert gas elimination technique (MIGET) and a dual-energy computed tomography (DECT) were performed and quantitatively analyzed for both tissue and blood volume. Variables related to the respiratory mechanics and invasive hemodynamics (PiCCO [Getinge, Sweden]) were also recorded. The sample (51 ± 15 yr; Pao2/Fio2, 172 ± 86 mmHg) had a mortality of 50%. The MIGET showed a shunt of 25 ± 16% and a dead space of 53 ± 11%. Ventilation and perfusion were mismatched (LogSD, Q, 0.86 ± 0.33). Unexpectedly, evidence of diffusion limitation or postpulmonary shunting was also found. In the well aerated regions, the blood volume was in excess compared to the tissue, while the opposite happened in the atelectasis. Shunt was proportional to the blood volume of the atelectasis (R2 = 0.70, P = 0.003). V˙A/Q˙T mismatch was correlated with the blood volume of the poorly aerated tissue (R2 = 0.54, P = 0.016). The overperfusion coefficient was related to Pao2/Fio2 (R2 = 0.66, P = 0.002), excess tissue mass (R2 = 0.84, P < 0.001), and Etco2/Paco2 (R2 = 0.63, P = 0.004). These data support the hypothesis of a highly multifactorial genesis of hypoxemia. Moreover, recent evidence from post-mortem studies (i.e., opening of intrapulmonary bronchopulmonary anastomosis) may explain the findings regarding the postpulmonary shunting. The hyperperfusion might be related to the disease severity.

Evaluation and clinical significance of gas exchange in patients with acute respiratory distress syndrome

Gas exchange abnormalities is the pathophysiology characteristic of acute respiratory distress syndrome (ARDS). The severity of gas exchange abnormalities not only reflect the severity and outcome of the disease, but could also be an important index to guide individual mechanical ventilation settings and evaluate the therapeutic effects of inhaled vasodilator. The common techniques to measure gas exchange include multiple inert gas elimination technique, automatic lung parameter estimator, electrical impedance tomography, and single-photon emission CT. Nowadays, bedside techniques and measurements for improving gas exchange function in ARDS patients are still limited. Therefore, the improvement and promotion of bedside real-time gas exchange monitoring technology may achieve the goal of personalized medicine in ARDS. This article reviewed the common evaluation methods of gas exchange function in ARDS and their significance, in order to pay more attention to the evaluation of gas exchange function and further improve the prognosis of patients with ARDS.

The Multiple Inert Gas Elimination Technique 50 years later: Lessons Learned

The Multiple Inert Gas Elimination Technique 50 years later: Lessons Learned

The effect of acute ventilation-perfusion mismatch on respiratory heat exchange in a porcine model.

BackgroundRespiratory heat exchange is an important physiological process occurring in the upper and lower respiratory tract and is usually completed when inspired gases reach the alveoli. Animal and human studies demonstrated that heat exchange can be modulated by altering pulmonary ventilation and perfusion. The purpose of this study was to examine the effect of acute ventilation-perfusion (V/Q) mismatch on respiratory heat exchange. In clinical practice, monitoring respiratory heat exchange might offer the possibility of real-time tracking of acute V/Q-mismatch.MethodsIn 11 anesthetized, mechanically ventilated pigs, V/Q-mismatch was established by means of four interventions: single lung ventilation, high cardiac output, occlusion of the left pulmonary artery and repeated whole-lung lavage. V/Q-distributions were determined by the multiple inert gas elimination technique (MIGET). Respiratory heat exchange was measured as respiratory enthalpy using the novel, pre-commercial VQm™ monitor (development stage, Rostrum Medical Innovations, Vancouver, CA). According to MIGET, shunt perfusion of low V/Q compartments increased during single lung ventilation, high cardiac output and whole-lung lavage, whereas dead space and ventilation of high V/Q compartments increased during occlusion of the left pulmonary artery and whole-lung lavage.ResultsBohr dead space increased after pulmonary artery occlusion and whole-lung lavage, venous admixture increased during single lung ventilation and whole-lung lavage, PaO2/FiO2 was decreased during all interventions. MIGET confirmed acute V/Q-mismatch. Respiratory enthalpy did not change significantly despite significant acute V/Q-mismatch.ConclusionClinically relevant V/Q-mismatch does not impair respiratory heat exchange in the absence of additional thermal stressors and may not have clinical utility in the detection of acute changes.

Ventilation-perfusion heterogeneity measured by the multiple inert gas elimination technique is minimally affected by intermittent breathing of 100% O2.

Proton magnetic resonance (MR) imaging to quantify regional ventilation–perfusion ( V˙A/Q˙) ratios combines specific ventilation imaging (SVI) and separate proton density and perfusion measures into a composite map. Specific ventilation imaging exploits the paramagnetic properties of O2, which alters the local MR signal intensity, in an FIO2‐dependent manner. Specific ventilation imaging data are acquired during five wash‐in/wash‐out cycles of breathing 21% O2 alternating with 100% O2 over ~20 min. This technique assumes that alternating FIO2 does not affect V˙A/Q˙ heterogeneity, but this is unproven. We tested the hypothesis that alternating FIO2 exposure increases V˙A/Q˙ mismatch in nine patients with abnormal pulmonary gas exchange and increased V˙A/Q˙ mismatch using the multiple inert gas elimination technique (MIGET).The following data were acquired (a) breathing air (baseline), (b) breathing alternating air/100% O2 during an emulated‐SVI protocol (eSVI), and (c) 20 min after ambient air breathing (recovery). MIGET heterogeneity indices of shunt, deadspace, ventilation versus V˙A/Q˙ ratio, LogSD V˙, and perfusion versus V˙A/Q˙ ratio, LogSD Q˙ were calculated. LogSD V˙ was not different between eSVI and baseline (1.04 ± 0.39 baseline, 1.05 ± 0.38 eSVI, p = .84); but was reduced compared to baseline during recovery (0.97 ± 0.39, p = .04). There was no significant difference in LogSD Q˙ across conditions (0.81 ± 0.30 baseline, 0.79 ± 0.15 eSVI, 0.79 ± 0.20 recovery; p = .54); Deadspace was not significantly different (p = .54) but shunt showed a borderline increase during eSVI (1.0% ± 1.0 baseline, 2.6% ± 2.9 eSVI; p = .052) likely from altered hypoxic pulmonary vasoconstriction and/or absorption atelectasis. Intermittent breathing of 100% O2 does not substantially alter V˙A/Q˙ matching and if SVI measurements are made after perfusion measurements, any potential effects will be minimized.

Red Bull Increases Heart Rate at Near Sea Level and Pulmonary Shunt Fraction at High Altitude in a Porcine Model.

Red Bull energy drink is popular among athletes, students and drivers for stimulating effects or enhancing physical performance. In previous work, Red Bull has been shown to exert manifold cardiovascular effects at rest and during exercise. Red Bull with caffeine as the main ingredient increases blood pressure in resting individuals, probably due to an increased release of (nor)-epinephrine. Red Bull has been shown to alter heart rate or leaving it unchanged. Little is known about possible effects of caffeinated energy drinks on pulmonary ventilation/perfusion distribution at sea level or at altitude. Here, we hypothesized a possible alteration of pulmonary blood flow in ambient air and in hypoxia after Red Bull consumption. We subjected eight anesthetized piglets in normoxia (FiO2 = 0.21) and in hypoxia (FiO2 = 0.13), respectively, to 10 mL/kg Red Bull ingestion. Another eight animals served as controls receiving an equivalent amount of saline. In addition to cardiovascular data, ventilation/perfusion distribution of the lung was assessed by using the multiple inert gas elimination technique (MIGET). Heart rate increased in normoxic conditions but was not different from controls in acute short-term hypoxia after oral Red Bull ingestion in piglets. For the first time, we demonstrate an increased fraction of pulmonary shunt with unchanged distribution of pulmonary blood flow after Red Bull administration in acute short-term hypoxia. In summary, these findings do not oppose moderate consumption of caffeinated energy drinks even at altitude at rest and during exercise.

Bi-Level ventilation decreases pulmonary shunt and modulates neuroinflammation in a cardiopulmonary resuscitation model.

BackgroundOptimal ventilation strategies during cardiopulmonary resuscitation are still heavily debated and poorly understood. So far, no convincing evidence could be presented in favour of outcome relevance and necessity of specific ventilation patterns. In recent years, alternative models to the guideline-based intermittent positive pressure ventilation (IPPV) have been proposed. In this randomized controlled trial, we evaluated a bi-level ventilation approach in a porcine model to assess possible physiological advantages for the pulmonary system as well as resulting changes in neuroinflammation compared to standard measures.MethodsSixteen male German landrace pigs were anesthetized and instrumented with arterial and venous catheters. Ventricular fibrillation was induced and the animals were left untreated and without ventilation for 4 minutes. After randomization, the animals were assigned to either the guideline-based group (IPPV, tidal volume 8–10 ml/kg, respiratory rate 10/min, FiO21.0) or the bi-level group (inspiratory pressure levels 15–17 cmH2O/5cmH2O, respiratory rate 10/min, FiO21.0). Mechanical chest compressions and interventional ventilation were initiated and after 5 minutes, blood samples, including ventilation/perfusion measurements via multiple inert gas elimination technique, were taken. After 8 minutes, advanced life support including adrenaline administration and defibrillations were started for up to 4 cycles. Animals achieving ROSC were monitored for 6 hours and lungs and brain tissue were harvested for further analyses.ResultsFive of the IPPV and four of the bi-level animals achieved ROSC. While there were no significant differences in gas exchange or hemodynamic values, bi-level treated animals showed less pulmonary shunt directly after ROSC and a tendency to lower inspiratory pressures during CPR. Additionally, cytokine expression of tumour necrosis factor alpha was significantly reduced in hippocampal tissue compared to IPPV animals.ConclusionBi-level ventilation with a constant positive end expiratory pressure and pressure-controlled ventilation is not inferior in terms of oxygenation and decarboxylation when compared to guideline-based IPPV ventilation. Additionally, bi-level ventilation showed signs for a potentially ameliorated neurological outcome as well as less pulmonary shunt following experimental resuscitation. Given the restrictions of the animal model, these advantages should be further examined.

Intra-pulmonary arteriovenous anastomoses and pulmonary gas exchange: evaluation by microspheres, contrast echocardiography and inert gas elimination.

Imaging techniques such as contrast echocardiography suggest that anatomical intra-pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung. To evaluate this discrepancy, we compared anatomical shunt with 25-µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET). Intra-pulmonary shunt measured by 25-µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt. A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange. The echocardiographic visualization of transpulmonary agitated saline microbubbles suggests that anatomical intra-pulmonary arteriovenous anastomoses are recruited during exercise, in hypoxia, and when cardiac output is increased pharmacologically. However, the multiple inert gas elimination technique (MIGET) shows insignificant right-to-left gas exchange shunt in normal humans and canines. To evaluate this discrepancy, we measured anatomical shunt with 25-µm microspheres and compared the results to contrast echocardiography and MIGET-determined gas exchange shunt in nine anaesthetized, ventilated canines. Data were acquired under the following conditions: (1) at baseline, (2) 2µgkg-1 min-1 i.v. dopamine, (3) 10µgkg-1 min-1 i.v. dobutamine, and (4) following creation of an intra-atrial shunt (in four animals). Right to left anatomical shunt was quantified by the number of 25-µm microspheres recovered in systemic arterial blood. Ventilation-perfusion mismatch and gas exchange shunt were quantified by MIGET and cardiac output by direct Fick. Left ventricular contrast scores were assessed by agitated saline bubble counts, and separately by appearance of 25-µm microspheres. Across all conditions, anatomical shunt measured by 25-µm microspheres was not different from gas exchange shunt measured by MIGET (microspheres: 2.3±7.4%; MIGET: 2.6±6.1%, P=0.64). Saline contrast bubble score was associated with microsphere shunt (ρ=0.60, P<0.001). Agitated saline contrast score had high sensitivity (100%) to detect a ≥1% shunt, but low specificity (22-48%). Gas exchange shunt by MIGET does not underestimate anatomical shunt measured using 25-µm microspheres. Contrast echocardiography is extremely sensitive, but not specific, often detecting small anatomical shunts which are inconsequential for gas exchange.

Precapillary pulmonary gas exchange is similar for oxygen and inert gases.

Precapillary gas exchange for oxygen has been documented in both humans and animals. It has been suggested that, if precapillary gas exchange occurs to a greater extent for inert gases than for oxygen, shunt and its effects on arterial oxygenation may be underestimated by the multiple inert gas elimination technique (MIGET). We evaluated fractional precapillary gas exchange in canines for O2 and two inert gases, sulphur hexafluoride and ethane, by measuring these gases in the proximal pulmonary artery, distal pulmonary artery (1cm proximal to the wedge position) and systemic artery. Some 12-19% of pulmonary gas exchange occurred within small (1.7mm in diameter or larger) pulmonary arteries and this was quantitatively similar for oxygen, sulphur hexafluoride and ethane. Under these experimental conditions, this suggests only minor effects of precapillary gas exchange on the magnitude of calculated shunt and the associated effect on pulmonary gas exchange estimated by MIGET. Some pulmonary gas exchange is known to occur proximal to the pulmonary capillary, although the magnitude of this gas exchange is uncertain, and it is unclear whether oxygen and inert gases are similarly affected. This has implications for measuring shunt and associated gas exchange consequences. By measuring respiratory and inert gas levels in the proximal pulmonary artery (P), a distal pulmonary artery 1cm proximal to the wedge position (using a 5-F catheter) (D) and a systemic artery (A), we evaluated precapillary gas exchange in 27 paired samples from seven anaesthetized, ventilated canines. Fractional precapillary gas exchange (F) was quantified for each gas as F=(P-D)/(P-A). The lowest solubility inert gases, sulphur hexafluoride (SF6 ) and ethane were used because, with higher solubility gases, the P-A difference is sufficiently small that experimental error prevents accurate assessment of F. Distal samples (n=12) with oxygen (O2 ) saturation values that were (within experimental error) equal to or above systemic arterial values, suggestive of retrograde capillary blood aspiration, were discarded, leaving 15 for analysis. D was significantly lower than P for SF6 (D/P=88.6±18.1%; P=0.03) and ethane (D/P=90.6±16.0%; P=0.04), indicating partial excretion of inert gas across small pulmonary arteries. Distal pulmonary arterial O2 saturation was significantly higher than proximal (74.1±6.8% vs. 69.0±4.9%; P=0.03). Fractional precapillary gas exchange was similar for SF6 , ethane and O2 (0.12±0.19, 0.12±0.20 and 0.19±0.26, respectively; P=0.54). Under these experimental conditions, 12-19% of pulmonary gas exchange occurs within the small pulmonary arteries and the extent is similar between oxygen and inert gases.

Breathing Life into Pulmonary Physiology: How Age and Body Weight Impair Oxygenation.

Breathing Life into Pulmonary Physiology: How Age and Body Weight Impair Oxygenation.

Oxygenation Impairment during Anesthesia: Influence of Age and Body Weight.

During anesthesia oxygenation is impaired, especially in the elderly or obese, but the mechanisms are uncertain. Pooled data were examined from 80 patients studied with multiple inert gas elimination technique and computed tomography. Oxygenation was impaired by anesthesia, more so with greater age or body mass index. The key contributors were low ventilation/perfusion ratio (likely airway closure) in the elderly and shunt (atelectasis) in the obese. Anesthesia is increasingly common in elderly and overweight patients and prompted the current study to explore mechanisms of age- and weight-dependent worsening of arterial oxygen tension (PaO2). This is a primary analysis of pooled data in patients with (1) American Society of Anesthesiologists (ASA) classification of 1; (2) normal forced vital capacity; (3) preoxygenation with an inspired oxygen fraction (FIO2) more than 0.8 and ventilated with FIO2 0.3 to 0.4; (4) measurements done during anesthesia before surgery. Eighty patients (21 women and 59 men, aged 19 to 69 yr, body mass index up to 30 kg/m2) were studied with multiple inert gas elimination technique to assess shunt and perfusion of poorly ventilated regions (low ventilation/perfusion ratio [(Equation is included in full-text article.)]) and computed tomography to assess atelectasis. PaO2/FIO2 was lower during anesthesia than awake (368; 291 to 470 [median; quartiles] vs. 441; 397 to 462 mm Hg; P = 0.003) and fell with increasing age and body mass index. Log shunt was best related to a quadratic function of age with largest shunt at 45 yr (r2 =0.17, P = 0.001). Log shunt was linearly related to body mass index (r2 = 0.15, P < 0.001). A multiple regression analysis including age, age2, and body mass index strengthened the association further (r2 = 0.27). Shunt was highly associated to atelectasis (r2 = 0.58, P < 0.001). Log low (Equation is included in full-text article.)showed a linear relation to age (r2 = 0.14, P = 0.001). PaO2/FIO2 ratio was impaired during anesthesia, and the impairment increased with age and body mass index. Shunt was related to atelectasis and was a more important cause of oxygenation impairment in middle-aged patients, whereas low(Equation is included in full-text article.), likely caused by airway closure, was more important in elderly patients. Shunt but not low(Equation is included in full-text article.)increased with increasing body mass index. Thus, increasing age and body mass index impaired gas exchange by different mechanisms during anesthesia.

Intravenous versus inhalational anaesthesia and lung ventilation-perfusion matching.

Lung gas exchange efficiency deteriorates during general anaesthesia due to ventilation–perfusion ( V/Q) scatter. Propofol total intravenous anaesthesia (TIVA) may preserve V/Q matching better than inhalational agents. We compared V/Q matching in patients randomized to either TIVA or sevoflurane anaesthesia, using deadspace and shunt measurements and the MIGET (Multiple Inert Gas Elimination Technique). Baseline arterial blood and mixed expired gas sampling was done before induction and repeated after one to two hours of relaxant general anaesthesia in 20 patients, supine with controlled ventilation at an FiO2of 0.3 and a target end-tidal PCO2of 30–35 mmHg. Blood samples for MIGET were processed after headspace equilibration by gas chromatography. The primary endpoint was a comparison of the two groups in the change from baseline of absolute difference between log standard deviation of ventilation and blood flow distributions (∂(σV−σQ)). Deadspace fraction increased and PaO2/FiO2ratio decreased across both groups overall with anaesthesia, but change in deadspace was not different between groups (mean (standard deviation, SD) sevoflurane 21.8% (11.7%) versus TIVA 20.5% (10.6%), P = 0.601). Change in PaO2/FiO2ratio was also similar between groups (mean (SD) sevoflurane −51.9 (69.1) mmHg versus TIVA −78.3 (76.9) mmHg, P = 0.43), as was change in shunt fraction (δQs/Qt mean (SD) sevoflurane −5.1% (12.6%) versus TIVA 0.4% (7.7%), P = 0.174). The primary endpoint ∂(σV−σQ) was not different between sevoflurane and propofol TIVA groups (mean (SD) 0.17 (0.81) versus 0.17 (0.29), P = 0.94). TIVA did not better preserve V/Q matching in patients undergoing anaesthesia with controlled ventilation compared with sevoflurane.

Measuring lung function in airways diseases: current and emerging techniques

Chronic airways diseases, including asthma, COPD and cystic fibrosis, cause significant morbidity and mortality and are associated with high healthcare expenditure, in the UK and worldwide. For patients with these...

Dynamics of acute respiratory distress syndrome development due to smoke inhalation injury: Implications for prolonged field care.

Smoke inhalation injury (SII) causes 30% to 40% mortality and will increase as a cause of death during prolonged field care. We used a combat relevant model of acute respiratory distress syndrome due to SII to study temporal changes in ventilation-perfusion (V/Q) matching, computed tomography (CT) scan data, and histopathology and hypothesized that SII leads to increase in shunt (Qshunt), V/Q mismatch, lung consolidation, and diffuse alveolar damage. Swine received severe SII and airway pressure release ventilation (APRV, n = 6), or conventional ARDSNet mechanical ventilation (MV) (CMV, n = 8). A control group without injury received volume controlled MV (CTRL, n = 6), The multiple inert gas elimination technique and CT were performed at baseline (BL), 0.5 hours, 1 hours, 2 hours, 24 hours, and 48 hours after injury. Diffuse alveolar damage scoring was performed post mortem. Significance at p less than 0.05: APRV versus CTRL; CMV versus CTRL; APRV versus CMV*; denotes changes versus BL. (1) SII caused increases in Qshunt more so in APRV than CMV group. Qshunt did not change in CTRL. (2) PaO2-to-FIO2 ratio (PFR) was lower in APRV versus CTRL at 2 hours (375 ± 62‡ vs. 549 ± 40) and 24 hours (126 ± 34‡* vs. 445 ± 5) and 48 hours (120 ± 41‡& vs. 430 ± 13). In CMV animals, PFR was lower versus CTRL and BL at 24 hours (238 ± 33) and 48 hours (98 ± 27). Qshunt correlated with PFR (r = 0.75, p < 0.0001, APRV and (r = 0.65, p < 0.0001, CMV). CT showed decrease in normally aerated lung, while poorly and nonaerated lung increased. Smoke inhalation injury leads to early development of shunt, V/Q mismatch, lung consolidation, and diffuse alveolar damage. These data substantiate the need for new point of injury interventions in the prolonged field care setting. Animal research.

Anatomical backgrounds on gas exchange parameters in the lung

Many problems regarding structure-function relationships have remained unsolved in the field of respiratory physiology. In the present review, we highlighted these uncertain issues from a variety of anatomical and physiological viewpoints. Model A of Weibel in which dichotomously branching airways are incorporated should be used for analyzing gas mixing in conducting and acinar airways. Acinus of Loeschcke is taken as an anatomical gas-exchange unit. Although it is difficult to define functional gas-exchange unit in a way entirely consistent with anatomical structures, acinus of Aschoff may serve as a functional gas-exchange unit in a first approximation. Based on anatomical and physiological perspectives, the multiple inert-gas elimination technique is thought to be highly effective for predicting ventilation-perfusion heterogeneity between acini of Aschoff under steady-state condition. Changes in effective alveolar PO2, the most important parameter in classical gas-exchange theory, are coherent with those in mixed alveolar PO2 decided from the multiple inert-gas elimination technique. Therefore, effective alveolar-arterial PO2 difference is considered useful for assessing gas-exchange abnormalities in lung periphery. However, one should be aware that although alveolar-arterial PO2 difference sensitively detects moderately low ventilation-perfusion regions causing hypoxemia, it is insensitive to abnormal gas exchange evoked by very low and high ventilation-perfusion regions. Pulmonary diffusing capacity for CO (DLCO) and the value corrected for alveolar volume (VAV), i.e. DLCO/VAV (KCO), are thought to be crucial for diagnosing alveolar-wall damages. DLCO-related parameters have higher sensitivity to detecting abnormalities in pulmonary microcirculation than those in the alveolocapillary membrane. We would like to recommend four categories derived from combining behaviors of DLCO with those of KCO for differential diagnosis on anatomically morbid states in alveolar walls: type-1 abnormality defined by decrease in both DLCO and KCO; type-2 abnormality by decrease in DLCO but increase in KCO; type-3 abnormality by decrease in DLCO but restricted rise in KCO; and type-4 abnormality by increase in both DLCO and KCO.

Near-real-time pulmonary shunt and dead space measurement with micropore membrane inlet mass spectrometry in pigs with induced pulmonary embolism or acute lung failure

The multiple inert gas elimination technique (MIGET) using gas chromatography (GC) is an established but time-consuming method of determining ventilation/perfusion (VA/Q) distributions. MIGET-when performed using Micropore Membrane Inlet Mass Spectrometry (MMIMS)-has been proven to correlate well with GC-MIGET and reduces analysis time substantially. We aimed at comparing shunt fractions and dead space derived from MMIMS-MIGET with Riley shunt and Bohr dead space, respectively. Thirty anesthetized pigs were randomly assigned to lavage or pulmonary embolism groups. Inert gas infusion (saline mixture of SF6, krypton, desflurane, enflurane, diethyl ether, acetone) was maintained, and after induction of lung damage, blood and breath samples were taken at 15-min intervals over 4h. The samples were injected into the MMIMS, and resultant retention and excretion data were translated to VA/Q distributions. We compared MMIMS-derived shunt (MM-S) to Riley shunt, and MMIMS-derived dead space (MM-VD) to Bohr dead space in 349 data pairs. MM-S was on average lower than Riley shunt (- 0.05 ± 0.10), with lower and upper limits of agreement of - 0.15 and 0.04, respectively. MM-VD was on average lower than Bohr dead space (- 0.09 ± 0.14), with lower and upper limits of agreement of - 0.24 and 0.05. MM-S and MM-VD correlated and agreed well with Riley shunt and with Bohr dead space. MM-S increased significantly after lung injury only in the lavage group, whereas MM-VD increased significantly in both groups. This is the first work evaluating and demonstrating the feasibility of near real-time VA/Q distribution measurements with the MIGET and the MMIMS methods.

A lifetime of pulmonary gas exchange.

Pulmonary gas exchange is the primary function of the lung, and during my lifetime, its measurement has passed through many stages. When I was born, many physiologists still believed that the lung secreted oxygen. When I was a medical student, the only way we had to recognize defective gas exchange was whether the patient was cyanosed. The advent of the oximeter soon showed that this sign could be very misleading. A breakthrough was the introduction of blood gas electrodes that could measure the PO 2, PCO 2, and pH of a small sample of arterial blood. It was soon recognized that the commonest cause of hypoxemia was ventilation‐perfusion inequality, and that this could also be responsible for CO 2 retention. In the early days, the understanding of the mechanisms of pulmonary gas exchange relied on graphical analysis because the oxygen and carbon dioxide dissociation curves are nonlinear and interdependent which precluded algebraic methods. However, with the introduction of digital computing, problems that had hitherto been impossible to tackle became amenable to study. A key advance was the development of the Multiple Inert Gas Elimination Technique. Now, noninvasive methods for measuring gas exchange show promise, and the whole subject continues to develop.

An in vitro lung model to assess true shunt fraction by multiple inert gas elimination.

The Multiple Inert Gas Elimination Technique, based on Micropore Membrane Inlet Mass Spectrometry, (MMIMS-MIGET) has been designed as a rapid and direct method to assess the full range of ventilation-to-perfusion (V/Q) ratios. MMIMS-MIGET distributions have not been assessed in an experimental setup with predefined V/Q-distributions. We aimed (I) to construct a novel in vitro lung model (IVLM) for the simulation of predefined V/Q distributions with five gas exchange compartments and (II) to correlate shunt fractions derived from MMIMS-MIGET with preset reference shunt values of the IVLM. Five hollow-fiber membrane oxygenators switched in parallel within a closed extracorporeal oxygenation circuit were ventilated with sweep gas (V) and perfused with human red cell suspension or saline (Q). Inert gas solution was infused into the perfusion circuit of the gas exchange assembly. Sweep gas flow (V) was kept constant and reference shunt fractions (IVLM-S) were established by bypassing one or more oxygenators with perfusate flow (Q). The derived shunt fractions (MM-S) were determined using MIGET by MMIMS from the retention data. Shunt derived by MMIMS-MIGET correlated well with preset reference shunt fractions. The in vitro lung model is a convenient system for the setup of predefined true shunt fractions in validation of MMIMS-MIGET.

Case Studies in Physiology: The Case of the Giant Giraffe.

N/A.