Physiology and Predictors of Impaired Gas Exchange in Infants with Bronchopulmonary Dysplasia.

Rationale: A sensitive outcome measure for infants with bronchopulmonary dysplasia would facilitate clinical benchmarking and enhance epidemiologic understanding, evaluation of clinical interventions, and outcome prediction.Objectives: Noninvasive assessment of pulmonary gas exchange in preterm infants with and without bronchopulmonary dysplasia to grade disease severity and to identify determinants of impaired gas exchange.Methods: This is a prospective observational study in very preterm infants. Inspired oxygen partial pressure (PiO2) was decreased stepwise to achieve oxygen saturation as measured by pulse oximetry (SpO2) that decreased from 95% to 86%. Right shift, V⋅a/Q⋅, and right-left shunt were derived from the resulting SpO2 versus PiO2 curve and compared with current disease severity classification. Potential determinants of shift, V⋅a/Q⋅, and shunt were identified using principal components analysis and multiple linear regression.Measurements and Main Results: A total of 219 infants with median (interquartile range) gestation of 28 weeks and 0 days (26 weeks and 0 days to 29 weeks and 0 days) had a valid study at 35 weeks and 4 days (34 weeks and 1 day to 39 weeks and 3 days) of postmenstrual age. Shift increased and V⋅a/Q⋅ decreased as severity of bronchopulmonary dysplasia increased. Infants with moderate-severe disease also had increased shunt. Extent of impaired gas exchange overlapped between severity groups. Infants requiring mechanical support but no supplemental oxygen at 36 weeks' postmenstrual age had similar values of shift, V⋅a/Q⋅, and shunt to preterm infants without bronchopulmonary dysplasia. Lower gestation and increased duration of invasive ventilation independently predicted increased shift, decreased V⋅a/Q⋅, and increased shunt. Shift was the most sensitive and specific index of the severity of bronchopulmonary dysplasia.Conclusions: Most infants with bronchopulmonary dysplasia have impaired oxygenation quantified by a simple, sensitive bedside test. Shift of the SpO2/PiO2 curve may be useful for prediction and measurement of preterm infant respiratory outcomes.

Evaluation of a computer program for non-invasive determination of pulmonary shunt and ventilation-perfusion mismatch.

We describe a three-compartment model (shunt and two perfused compartments) to analyse the relationship between inspired oxygen (FIO2) and arterial oxygen saturation (SaO2) in terms of pulmonary shunt and ventilation-perfusion ratio (VA/Q). The program was tested using 24 exact datasets, each with six pairs of FIO2 and SaO2 data points with known VA/Q and shunt, generated by a complex calculator of gas exchange. Additional datasets were created by adding noise and rounding the exact sets, and by reducing the number of data points per dataset. The importance of the oxyhaemoglobin dissociation curve and the arterio-venous difference in oxygen content (avDO2) were also tested. Analysis using the three compartment model was more accurate than the two compartment model and less affected by data degradation. The absolute error in shunt estimation was never more than 2.2 % for the exact and rounded datasets, but the error in VA/Q estimation was -29 to 19 % of the true value (10th-90th centiles). The characteristics of the well-ventilated compartment were not determined accurately. At extremes of cardiac output, an assumed value of avDO2 resulted in significant errors. It is probably advantageous to correct for foetal haemoglobin in neonatal datasets. Analysis of FIO2 versus SaO2 datasets using a three compartment model provides accurate estimates of shunt and VA/Q when arterio-venous difference in oxygen content is known. The estimates may have value as objective measures of gas exchange, and as a visual guide for oxygen therapy.

Pathophysiology of gas exchange impairment in extreme prematurity: Insights from combining volumetric capnography and measurements of ventilation/perfusion ratio.

Background: Infants born extremely preterm often suffer from respiratory disease and are invasively ventilated. We aimed to test the hypothesis that gas exchange in ventilated extremely preterm infants occurs both at the level of the alveoli and via mixing of fresh deadspace gas in the airways. Methods: We measured the normalised slopes of phase II and phase III of volumetric capnography and related them with non-invasive measurements of ventilation to perfusion ratio (VA/Q) and right-to-left shunt in ventilated extremely preterm infants studied at one week of life. Cardiac right-to-left shunt was excluded by concurrent echocardiography. Results: We studied 25 infants (15 male) with a median (range) gestational age of 26.0 (22.9-27.9) weeks and birth weight of 795 (515-1,165) grams. The median (IQR) VA/Q was 0.52 (0.46-0.56) and shunt was 8 (2-13) %. The median (IQR) normalised slope of phase II was 99.6 (82.7-116.1) mmHg and of phase III was 24.6 (16.9-35.0) mmHg. The VA/Q was significantly related to the normalised slope of phase III (ρ = -0.573, p = 0.016) but not to the slope of phase II (ρ = 0.045, p = 0.770). The right-to-left shunt was not independently associated with either the slope of phase II or the slope of phase III after adjusting for confounding parameters. Conclusions: Abnormal gas exchange in ventilated extremely preterm infants was associated with lung disease at the alveolar level. Abnormal gas exchange at the level of the airways was not associated with quantified indices of gas exchange impairment.

Unstable SpO2 in preterm infants: The key role of reduced ventilation to perfusion ratio.

Introduction: Instability of peripheral oxyhemoglobin saturation (SpO2) in preterm infants is correlated with late disability and is poorly understood. We hypothesised that a reduced ventilation to perfusion ratio (VA/Q) is the key predisposing factor for SpO2 instability. Methods: We first used a mathematical model to compare the effects of reduced VA/Q or shunt on SaO2 stability (SaO2 and SpO2 are used for model and clinical studies respectively). Stability was inferred from the slope of the SaO2 vs. inspired oxygen pressure (P IO2) curve as it intersects the 21 kPa P IO2 line (breathing air). Then, in a tertiary neonatal intensive care unit, paired hourly readings of SpO2 and P IO2 were recorded over a 24 h period in week old extremely preterm infants. We noted SpO2 variability and used an algorithm to derive VA/Q and shunt from the paired SpO2 and P IO2 measurements. Results: Our model predicted that when VA/Q < 0.4, a 1% change in P IO2 results in >8% fluctuation in SaO2 at 21 kPa P IO2. In contrast, when a 20% intrapulmonary shunt was included in the model, a 1% change in P IO2 results in <1% fluctuation in the SaO2. Moreover, further reducing the VA/Q from 0.4 to 0.3 at 21 kPa P IO2 resulted in a 24% fall in SaO2. All 31 preterm infants [mean gestation (±standard deviation) 26.2 (±1) week] had VA/Q < 0.74 (normal >0.85) but only two infants had increased shunt at 1.1 (±0.5) weeks' postnatal age. Median (IQR) SpO2 fluctuation was 8 (7)%. The greatest SpO2 fluctuations were seen in infants with VA/Q < 0.52 (n = 10): SpO2 fluctuations ranged from 11%-17% at a constant P IO2 when VA/Q < 0.52. Two infants had reduced VA/Q and increased shunt (21% and 27%) which resolved into low VA/Q after 3-6 h. Discussion: Routine monitoring of P IO2 and SpO2 can be used to derive a hitherto elusive measure of VA/Q. Predisposition to SpO2 instability results from reduced VA/Q rather than increased intrapulmonary shunt in preterm infants with cardiorespiratory disease. SpO2 instability can be prevented by a small increase in P IO2.

Profound hypoxemia in pulmonary patients in airline-equivalent hypoxia: roles of VA/Q and shunt.

BACKGROUND: Airliners at cruise altitudes have cabin pressures of 84.3-75.2 kPa, equivalent to 5000-8000 ft. Supplementary oxygen in flight is generally advised for patients whose ground-level arterial oxygen saturation by pulse oximetry (SpO2) is < 92%. However, some pulmonary patients with values above that threshold nevertheless develop profound in-flight hypoxemia (SpO2 < or = 82%) as cabin pressure falls. This experiment measured the contributions of ventilation-perfusion ratio (VA/Q) and pulmonary shunt to that phenomenon. METHODS: Air/nitrogen mixtures were used to expose 18 patients with pulmonary dysfunction to PIO2 = 15 kPa. VA/Q was estimated from right shift of the steep phase of the PIO2 vs. SpO2 curve along the PO2 axis. Shunt was estimated from change of shape and downward shift of the same curve. RESULTS: During hypoxia, the lowest observed SpO2 was correlated with reduced VA/Q (R2 = 0.89). Of 10 patients with VA/Q < or = 0.69, 9 developed profound hypoxia even though 5 of those had SpO2 > or = 92% at ground level; patients with VA/Q > 0.75 maintained SpO2% > or = 84%. Hypoxemia did not correlate with shunt for the group as a whole, but eight patients with VA/Q > or = 0.73 and shunts in the range 6.6-20.8% showed such a correlation (R2 = 0.8). CONCLUSION: In patients with similar ground-level SpO2, profound hypoxemia was more likely to develop in those with reduced VA/Q (< or = 0.69) as opposed to those with shunts of 20%. Measurement of VA/Q and shunt during hypoxic hypoxia improves prediction of patient need for supplementary oxygen on airline flights.