Progressive changes in pulmonary gas exchange during invasive respiratory support for COVID-19 associated acute respiratory failure: A retrospective study of the association with 90-day mortality.

BACKGROUND: Ratio of arterial pressure of oxygen and fraction of inspired oxygen (P/F ratio) together with the fractional dead space (Vd/Vt) provides a global assessment of pulmonary gas exchange. The aim of this study was to assess the potential value of these variables to prognosticate 90-day survival in patients with COVID-19 associated ARDS admitted to the Intensive Care Unit (ICU) for invasive ventilatory support. METHODS: In this single-center observational, retrospective study, P/F ratios and Vd/Vt were assessed up to 4 weeks after ICU-admission. Measurements from the first 2 weeks were used to evaluate the predictive value of P/F ratio and Vd/Vt for 90-day mortality and reported by the adjusted hazard ratio (HR) and 95% confidence intervals [95%CI] by Cox proportional hazard regression. RESULTS: Almost 20,000 blood gases in 130 patients were analyzed. The overall 90-day mortality was 30% and using the data from the first ICU week, the HR was 0.85 [0.77-0.94] for every 10 mmHg increase in P/F ratio and 1.61 [1.20-2.16] for every 0.1 increase in Vd/Vt. In the second week, the HR for 90-day mortality was 0.82 [0.75-0.89] for every 10 mmHg increase in P/F ratio and 1.97 [1.42-2.73] for every 0.1 increase in Vd/Vt. CONCLUSION: The progressive changes in P/F ratio and Vd/Vt in the first 2 weeks of invasive ventilatory support for COVID-19 ARDS were significant predictors for 90-day mortality.

Arterial to end-tidal CO2 gradients during isocapnic hyperventilation.

Isocapnic hyperventilation (ICHV) is occasionally used to maintain the end-expired CO2 partial pressure (PETCO2) when the inspired CO2 (PICO2) rises. Whether maintaining PETCO2 with ICHV during an increase of the PICO2 also maintains arterial PCO2 (PaCO2) remains poorly documented. 12 ASA PS I-II subjects undergoing a robot-assisted radical prostatectomy (RARP) (n = 11) or cystectomy (n = 1) under general endotracheal anesthesia with sevoflurane in O2/air (40% inspired O2) were enrolled. PICO2 was sequentially increased from 0 to 0.5, 1.0, 1.5 and 2% by adding CO2 to the inspiratory limb of the circle system, while increasing ventilation to a target PETCO2 of 4.7-4.9% by adjusting respiratory rate during controlled mechanical ventilation. Pa-ETCO2 gradients were determined after a 15 min equilibration period at each PICO2 level and compared using ANOVA. Mean (standard deviation) age, height, and weight were 66 (6) years, 171 (6) cm, and 75 (8) kg, respectively. Capnograms were normal and hemodynamic parameters remained stable. PETCO2 could be maintained within 4.7-4.9% in all subjects at all times except in 1 subject with 1.5% PICO2 and 5 subjects with 2.0% PICO2; data from the one subject in whom both 1.5 and 2.0% PICO2 resulted in PETCO2 > 5.1% were excluded from analysis. Pa-ETCO2 gradients did not change when PICO2 increased. The effect of a modest rise of PICO2 up to 1.5% on PETCO2 during RARP can be readily overcome by increasing ventilation without altering the Pa-ETCO2 gradients. At higher PICO2, airway pressures may become a limiting factor, which requires further study.

Thrombomodulin is associated with increased mortality and organ failure in mechanically ventilated children with acute respiratory failure: biomarker analysis from a multicenter randomized controlled trial.

BACKGROUND: Acute respiratory failure (ARF) can progress to acute respiratory distress syndrome and death. Biomarkers may allow for risk stratification and prognostic enrichment in ARF. Thrombomodulin (TM) is a transmembrane antithrombotic mediator expressed in endothelial cells. It is cleaved into its soluble form (sTM) during inflammation and vascular injury. Levels of sTM correlate with inflammation and end organ dysfunction. METHODS: This was a prospective observational study of 432 patients aged 2 weeks-17 years requiring invasive mechanical ventilation. It was ancillary to the multicenter clinical trial, Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE). After consent, patients had up to 3 plasma samples collected at 24-h intervals within 5 days after intubation. sTM was assayed by ELISA. The Hazard ratio (HR) for 90-day mortality was determined by Cox regression. Mixed effect models (MEM) were used to test for association with extrapulmonary multiorgan failure (MOF) and oxygenation index (OI). Age, race, sex and PRISM-III scores were used as confounding variables for multivariable analyses. RESULTS: sTM values ranged from 16.6 to 670.9 ng/ml within 5 days after intubation. Higher sTM was associated with increased 90-day mortality (n = 432, adjusted HR = 1.003, p = 0.02) and worse OI in the first 5 days after intubation (n = 252, Estimate = 0.02, p < 0.01). Both initial and slope of sTM were associated with increased extrapulmonary MOF in unadjusted and adjusted analyses (Intercept, Estimate = 0.003, p < 0.0001; and slope, Estimate = 0.01, p = 0.0009, n = 386). CONCLUSIONS: Plasma sTM is associated with mortality, severity of hypoxic respiratory failure and worsening extrapulmonary MOF in children with ARF. This suggests a role of vascular injury in the pathogenesis of ARF and provides potential applicability towards targeted therapies. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00814099 . In healthy lung endothelium, thrombomodulin (TM) recruits thrombin to activate Protein-C (PC/APC), that inhibits plasminogen activator-1 (PAI-1) and thrombosis. In inflamed and damaged endothelium, TM is cleaved into its soluble form (sTM), precluding its usual regulation of thrombosis. In this study, we measured plasma sTM levels in pediatric patients with respiratory failure and found that sTM correlated with mortality and other clinical markers of poor outcomes.

Increased physiological dead space in mechanically ventilated COVID-19 patients recovering from severe acute respiratory distress syndrome: a case report.

BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) is spreading globally. Recently, several articles have mentioned that the early acute respiratory distress syndrome (ARDS) caused by COVID-19 significantly differ from those of ARDS due to other causes. Actually, we newly observed that some mechanically ventilated COVID-19 patients recovering from severe ARDS (more than 14 days after invasive ventilation) often experienced evidently gradual increases in CO2 retention and minute ventilation. However, the underlying mechanics remain unclear. CASE PRESENTATION: To explain these pathophysiological features and discuss the ventilatory strategy during the late phase of severe ARDS in COVID-19 patients, we first used a metabolic module on a General Electric R860 ventilator (Engstrom Carestation; GE Healthcare, USA) to monitor parameters related to gas metabolism, lung mechanics and physiological dead space in two COVID-19 patients. We found that remarkably decreased ventilatory efficiency (e.g., the ratio of dead space to tidal volume 70-80%, arterial to end-tidal CO2 difference 18-23 mmHg and ventilatory ratio 3-4) and hypermetabolism (oxygen consumption 300-400 ml/min, CO2 elimination 200-300 ml/min) may explain why these patients experienced more severe respiratory distress and CO2 retention in the late phase of ARDS caused by COVID-19. CONCLUSION: During the recovery period of ARDS among mechanically-ventilated COVID-19 patients, attention should be paid to the monitoring of physiological dead space and metabolism. Tidal volume (8-9 ml/kg) could be increased appropriately under the limited plateau pressure; however, barotrauma should still be kept in mind.

Respiratory muscle weakness increases dead-space ventilation ratio aggravating ventilation-perfusion mismatch during exercise in patients with chronic heart failure.

BACKGROUND AND OBJECTIVE: Respiratory muscle weakness causes fatigue in these muscles during exercise and thereby increases dead-space ventilation ratio with decreased tidal volume. However, it remains unclear whether respiratory muscle weakness aggravates ventilation-perfusion mismatch through the increased dead-space ventilation ratio. In ventilation-perfusion mismatch during exercise, minute ventilation versus carbon dioxide production (VE/VCO2 ) slope > 34 is an indicator of poor prognosis in patients with chronic heart failure (CHF). We examined the relationship of respiratory muscle weakness with dead-space ventilation ratio and ventilation-perfusion mismatch during exercise and clarified whether respiratory muscle weakness was a clinical predictor of VE/VCO2 slope > 34 in patients with CHF. METHODS: Maximal inspiratory pressure (PImax ) was measured as respiratory muscle strength 2 months after hospital discharge in 256 compensated patients with CHF. During cardiopulmonary exercise test, we assessed minute dead-space ventilation versus VE (VD/VE ratio) as dead-space ventilation ratio and VE/VCO2 slope as ventilation-perfusion mismatch. Patients were divided into low, moderate and high PImax groups based on the PImax tertile. We investigated determinants of VE/VCO2 slope > 34 among these groups. RESULTS: The low PImax group showed significantly higher VD/VE ratios at 50% of peak workload and at peak workload and higher VE/VCO2 slope than the other two groups (P < 0.001, respectively). PImax was a significant independent determinant of VE/VCO2 slope > 34 (odds ratio (OR): 0.67, 95% CI: 0.54-0.82) with area under the receiver operating characteristic curve of 0.812 (95% CI: 0.750-0.874). CONCLUSION: Respiratory muscle weakness was associated with an increased dead-space ventilation ratio aggravating ventilation-perfusion mismatch during exercise in patients with CHF.

Pulmonary Perfusion Using Intrabronchial Capnography in Pulmonary Artery Stenosis.

Stenting at the flow-limiting segment can improve the ventilation-perfusion ratio in patients with central airway stenosis. However, there is no quantitative examination for assessing the perfusion status during interventional bronchoscopy. Intrabronchial capnography can estimate regional gas exchange by measuring carbon dioxide concentration. We herein report a case of bilateral bronchial stenosis where stenting was able to improve ventilation-perfusion ratio using intrabronchial capnography. A 44-year-old man was admitted to our institution with orthopnea. Chest computed tomography showed an extrinsic compression at the bilateral main bronchus and right pulmonary artery due to a mediastinal mass. After introduction of general anesthesia, arterial oxygen tension suddenly decreased in the supine position. After initial stenting, an increase was seen in ventilation at the right lung; however, a ventilation-perfusion mismatch occurred due to an increase in dead-space ventilation at the right pulmonary artery stenosis. Intrabronchial capnography was an effective modality to confirm the regional perfusion status during interventional bronchoscopy in real time.

Incidence of Severe Hypoxemia in Anesthetized Horses Undergoing Emergency Exploratory Laparotomy.

Prevalence and risk factors of severe hypoxemia in anesthetized horses undergoing emergency exploratory laparotomy are sparsely documented. The aim of this study was to report incidence of severe hypoxemia ( PaO2 < 60 mmHg) in horses undergoing emergency exploratory laparotomy and identify potential risk factors for this complication. A single center retrospective cross sectional designed was used. Clinical data of 714 horses undergoing general anesthesia for emergency explorative laparotomy were reviewed. A backward stepwise elimination procedure was used to determine the final multivariable logistic regression model; all covariables with univariable P-values <.25 were incorporated, with retention of covariables with Wald P-values <.05 at each step, in order to determine which explanatory variables would be included in the final model. The overall incidence of severe hypoxemia in our population was 15.3%. Multivariable logistic regression analysis showed that increasing body weight (odds ratio [OR] 1.01, 95% confidence interval [CI] 1.0-1.01, P = .002), colon torsion (OR 3.0, 95% CI 1.3-6.8, P = .006), increased dead space ventilation (OR 1.06, 95% CI 1.04-1.09, P ≤ .001), shorter time between induction of anesthesia and collection of arterial blood gas samples (OR 0.98, 95% CI 0.98-0.99, P ≤ .001) and intratracheal aerosolized salbutamol (OR 13.5, 95% CI 7.6-24, P ≤ .001) were associated with the outcome. The incidence of hypoxemia found in our study was in line with previous literature. Increasing body weight, colon torsion and shorter time between the time of induction of anesthesia and collection of arterial blood gas samples represented risk factors for hypoxemia.

Microcirculatory dysfunction and dead-space ventilation in early ARDS: a hypothesis-generating observational study.

BACKGROUND: Ventilation/perfusion inequalities impair gas exchange in acute respiratory distress syndrome (ARDS). Although increased dead-space ventilation (VD/VT) has been described in ARDS, its mechanism is not clearly understood. We sought to evaluate the relationships between dynamic variations in VD/VT and extra-pulmonary microcirculatory blood flow detected at sublingual mucosa hypothesizing that an altered microcirculation, which is a generalized phenomenon during severe inflammatory conditions, could influence ventilation/perfusion mismatching manifested by increases in VD/VT fraction during early stages of ARDS. METHODS: Forty-two consecutive patients with early moderate and severe ARDS were included. PEEP was set targeting the best respiratory-system compliance after a PEEP-decremental recruitment maneuver. After 60 min of stabilization, hemodynamics and respiratory mechanics were recorded and blood gases collected. VD/VT was calculated from the CO2 production ([Formula: see text]) and CO2 exhaled fraction ([Formula: see text]) measurements by volumetric capnography. Sublingual microcirculatory images were simultaneously acquired using a sidestream dark-field device for an ulterior blinded semi-quantitative analysis. All measurements were repeated 24 h after. RESULTS: Percentage of small vessels perfused (PPV) and microcirculatory flow index (MFI) were inverse and significantly related to VD/VT at baseline (Spearman's rho = - 0.76 and - 0.63, p < 0.001; R2 = 0.63, and 0.48, p < 0.001, respectively) and 24 h after (Spearman's rho = - 0.71, and - 0.65; p < 0.001; R2 = 0.66 and 0.60, p < 0.001, respectively). Other respiratory, macro-hemodynamic and oxygenation parameters did not correlate with VD/VT. Variations in PPV between baseline and 24 h were inverse and significantly related to simultaneous changes in VD/VT (Spearman's rho = - 0.66, p < 0.001; R2 = 0.67, p < 0.001). CONCLUSION: Increased heterogeneity of microcirculatory blood flow evaluated at sublingual mucosa seems to be related to increases in VD/VT, while respiratory mechanics and oxygenation parameters do not. Whether there is a cause-effect relationship between microcirculatory dysfunction and dead-space ventilation in ARDS should be addressed in future research.

Empirical Probability of Positive Response to PEEP Changes and Mechanical Ventilation Factors Associated With Improved Oxygenation During Pediatric Ventilation.

BACKGROUND: PEEP is titrated to improve oxygenation during mechanical ventilation. It is clinically desirable to identify factors that are associated with a clinical improvement or deterioration following a PEEP change. However, these factors have not been adequately described in the literature. Therefore, we aimed to quantify the empirical probability of PEEP changes having a positive effect upon oxygenation, compliance of the respiratory system (CRS), and the ratio of dead space to tidal volume (VD/VT). Further, clinical factors associated with positive response during pediatric mechanical ventilation are described. METHODS: Mechanically ventilated pediatric subjects in the ICU were eligible for inclusion in the study. During PEEP increases (PEEPincrease), a responder was defined as having an improved SpO2 /FIO2 ratio; non-responders demonstrated a worsening SpO2 /FIO2 ratio in the following hour. When PEEP was decreased (PEEPdecrease), a responder was anyone who maintained or increased the SpO2 /FIO2 ratio; non-responders demonstrated a worsening SpO2 /FIO2 ratio. Features from continuous mechanical ventilation variables were extracted, and differences between responders and non-responders were identified. RESULTS: 286 PEEP change cases were eligible for analysis in 76 subjects. For PEEPincrease cases, the empirical probability of positive response was 56%, 67%, and 54% for oxygenation, CRS, and VD/VT, respectively. The median SpO2 /FIO2 increase was 13. For PEEPdecrease, the empirical probability of response was 46%, 53%, and 46% for oxygenation, CRS, and VD/VT, respectively. PEEPincrease responders had higher FIO2 requirements (70.8 vs 52.5%, P < .001), mean airway pressure (14.0 vs 12.9 cm H2O, P = .03), and oxygen saturation index (9.9 vs 7.5, P = .002) versus non-responders. For PEEPdecrease, VD/VT was lower in responders (0.46 vs 0.50, P = .031). CONCLUSIONS: In children requiring mechanical ventilation, the responder rate was modest for both PEEPincrease and PEEPdecrease cases. These data suggest that PEEP titration often does not have the desired clinical effect, and predicting which patients will manifest a positive response is complex, requiring more sophisticated means of assessing individual subjects.

Physiological insights of exercise hyperventilation in arterial and chronic thromboembolic pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) patients show, during exercise, an excessive increase in ventilation (VE) compared to carbon dioxide output (VCO2), determining a high VE/VCO2 slope. There are several possible causes, including an elevated dead space ventilation (VD), VE/perfusion (Q) mismatch and/or an enhanced peripheral or central chemoreceptor activity. We evaluated the causes of exercise hyperventilation in PH patients. METHODS: Eighteen group I and IV PH patients underwent cardiopulmonary exercise test with blood gas analysis at every minute. VE, alveolar ventilation (VA) and VD vs. VCO2 relationship were calculated. Resting chemoreceptor sensitivity was analyzed through hypoxia/hypercapnia tests. RESULTS: PeakVO2 and VE/VCO2 slopes were 1.06±0.24l/min and 39.1±9.0, respectively. Throughout the exercise, 30% of VE was due to VD. VE/VCO2 slope significantly correlated with VD/VCO2 slope (r=0.82, p<0.001) but not with VA/VCO2 slope (r=0.3, p=ns). Peak exercise end-tidal CO2 (PetCO2) correlated with VD/VCO2 slope (r=-0.79, p<0.001) and VE/VCO2 slope (r=-0.91, p<0.001). Dead space(DS)/Tidal volume and P(arterial-et)CO2 were elevated without arterial hypoxemia suggesting a high VE/Q mismatch. Chemoreceptor peripheral response to hypoxia and central CO2 response were both enhanced being peripheral responses to hypoxia and hypercapnia 0.416±0.402 (normal ref values=0.285±0.221) l/min/O2Sat and 0.076±0.047 (0.066±0.430) l/min/mmHg, respectively; central hypercapnic chemosensitivity was 4.475±3.99 (2.352±0.936) l/min/mmHg. CONCLUSIONS: Increased DS, VE/Q mismatch and chemorecptor response are among the main mechanisms involved in exercise hyperventilation in PH. ClinicalTrial.govNCT02892981.

Association of dead space ventilation and prolonged ventilation after repair of tetralogy of Fallot with pulmonary atresia.

BACKGROUND: We set out to determine whether patients with tetralogy of Fallot with pulmonary atresia and major aortopulmonary collateral arteries (TOF/PA/MAPCA) are at risk for elevated dead space ventilation fraction (VD/VT), and whether this is associated with prolonged mechanical ventilation. We hypothesized that elevated VD/VT (>20%) in the first 24 hours after unifocalization surgery is associated with increased risk for prolonged mechanical ventilation (>7 days). METHODS: All patients with TOF/PA/MAPCA undergoing unifocalization surgery between January 2003 and December 2015 were included in this study. Average VD/VT was calculated over the first 24 hours after surgery. Demographic and surgical data were collected. Outcome data included duration of mechanical ventilation. Patients were separated into 2 groups: elevated VD/VT and normal DVSF. Groups were compared using the Student t test, Wilcoxon rank-sum test, and χ2 test. Univariable and multivariable regression analyses were performed with VD/VT as a continuous variable to test for association. RESULTS: Of the 265 included patients, 127 (48%) had an elevated VD/VT. The 2 groups did not differ significantly in any demographic characteristic. Patients with an elevated VD/VT had longer cardiopulmonary bypass times (P = .03), were more likely to have delayed sternal closure, and more likely to have prolonged respiratory failure (odds ratio, 2.2; 95% confidence interval, 1.2-4.0; P = .007). The percent VD/VT was associated with duration of mechanical ventilation in univariable (P < .001) and multivariable (P < .001) regression analyses when controlled for age, weight and bypass time. CONCLUSIONS: Elevated postoperative VD/VT is associated with prolonged mechanical ventilation in patients with TOF/PA/MAPCA following unifocalization. Elevated postoperative VD/VT may be an early indicator of patients who will require prolonged duration of mechanical ventilation, allowing optimization of medical management to promote better outcomes.

Effects of low oxygen dead space ventilation and breath-holding test in evaluating cerebrovascular reactivity: A comparative observation.

OBJECTIVE: This study aims to explore the application prospect of low oxygen dead space ventilation (LODSV) in evaluating vasomotor reactivity (VMR) by comparison between LODSV and breath-holding test (BHT). METHODS: Outpatient or inpatient patients who underwent transcranial Doppler sonography (TCD) were enrolled into this study. These patients successively underwent BHT and LODSV. The cooperation degree, tolerance conditions and adverse reactions in patients were recorded, and VMR was calculated, compared and analyzed. RESULTS: Patients had poor cooperation during BHT. Except for compensatory tachypnea after BHT, patients basically had no adverse reaction. The main manifestations of patients undergoing LODSV were deepened breathing and accelerated frequency in the end of the ventilation, and increased heart rate and a slight decline in pulse oxygen that rapidly recovered after ventilation. The increase rate of blood flow velocity in patients undergoing LODSV was significantly higher than in BHT (P<0.001), and its calculated VMR value was approximately 15% higher than BHT (P<0.001). BHT revealed a monophasic curve that slightly descends and rapidly increases, and LODSV revealed a curve that descends for a short time and slowly increases with a platform. CONCLUSION: LODSV can effectively eliminate the affect of poor cooperation in patients, and avoid intolerance caused by hypoxia. Hence, VMR value is more accurate than that determined by BHT; and this can reflect the maximum reaction ability of the blood vessels. Therefore, this method has higher clinical application value.

Nasal high flow reduces hypercapnia by clearance of anatomical dead space in a COPD patient.

Chronic obstructive pulmonary disease (COPD) with hypercapnia is associated with increased mortality. Non-invasive ventilation (NIV) can lower hypercapnia and ventilator loads but is hampered by a low adherence rate leaving a majority of patients insufficiently treated. Recently, nasal high flow (NHF) has been introduced in the acute setting in adults, too. It is an open nasal cannula system for delivering warm and humidified air or oxygen at high flow rates (2-50 L/min) assisting ventilation. It was shown that this treatment can improve hypercapnia. The mechanism of reducing arterial carbon dioxide (CO2) is proposed through a reduction in nasal dead space ventilation, but there are no studies in which dead space volume was measured in spontaneously breathing subjects. In our case report we measured in a tracheostomized COPD patient CO2 and pressure via sealed ports in the tracheostomy cap and monitored transcutaneous CO2 and tidal volumes. NHF (30 L/min mixed with 3 L/min oxygen) was administered repeatedly at 15-minutes intervals. Inspired CO2 decreased instantly with onset of NHF, followed by a reduction in transcutaneous/arterial CO2. Minute ventilation on nasal high flow was also reduced by 700 ml, indicating that nasal high flow led to a reduction of dead space ventilation thereby improving alveolar ventilation. In conclusion, NHF assist ventilation through clearance of anatomical dead space, which improves alveolar ventilation. Since the reduction in hypercapnia was similar to that reported with effective NIV treatment NHF may become an alternative to NIV in hypercapnic respiratory failure.

Cardiovascular and respiratory dysfunction in chronic obstructive pulmonary disease complicated by impaired peripheral oxygenation.

BACKGROUND: Impaired peripheral oxygenation (IPO)-related variables readily achieved with cardiopulmonary exercise testing (CPET) represent cardiovascular dysfunction. These variables include peak oxygen uptake ( [Formula: see text] predicted, anaerobic threshold [Formula: see text] predicted, [Formula: see text] rate slope <8.6 mL/watt, oxygen pulse <80% predicted, and ventilatory equivalents for O2 and CO2 at nadir of >31 and >34, respectively. Some of these six variables may be normal while the others are abnormal in patients with chronic obstructive pulmonary disease (COPD). This may result in confusion when using the interpretation algorithm for diagnostic purposes. We therefore hypothesized that patients found to have abnormal values for all six variables would have worse cardiovascular function than patients with abnormal values for none or some of these variables. METHODS: In this cross-sectional comparative study, 58 COPD patients attending a university teaching hospital underwent symptom-limited CPET with multiple lactate measurements. Patients with abnormal values in all six IPO-related variables were assigned to an IPO group while those who did not meet the requirements for the IPO group were assigned to a non-IPO group. Cardiovascular function was measured by two-dimensional echocardiography and [Formula: see text], and respiratory dynamics were compared between the two groups. RESULTS: Fourteen IPO and 43 non-IPO patients were entered into the study. Both groups were similar with regard to left ventricular ejection fraction and right ventricular morphology (P>0.05 for both). At peak exercise, both groups reached a similar heart rate level and [Formula: see text]. The IPO patients had an unfavorable dead space to tidal volume ratio, mean inspiratory tidal flow, and shallow breathing (P<0.05-P<0.001). CONCLUSION: Our IPO and non-IPO patients with COPD had similar cardiovascular performance at rest and at peak exercise, indicating that IPO variables are non-specific for cardiovascular function in these patients. COPD patients with full IPO variables have more deranged ventilatory function.