Mechanical Ventilation Redistributes Blood to Poorly Ventilated Areas in Experimental Lung Injury

Abstract

Objectives: Determine the intra-tidal regional gas and blood volume distributions at different levels of atelectasis in experimental lung injury. Test the hypotheses that pulmonary aeration and blood volume matching is reduced during inspiration in the setting of minimal tidal recruitment/derecruitment and that this mismatching is an important determinant of hypoxemia.

Design: Preclinical study.

Setting: Research laboratory.

Subjects: Seven anesthetized pigs 28.7 kg (SD, 2.1 kg).

Interventions: All animals received a saline-lavage surfactant depletion lung injury model. Positive end-expiratory pressure was varied between 0 and 20 cm H2O to induce different levels of atelectasis.

Measurements and main results: Dynamic dual-energy CT images of a juxtadiaphragmatic slice were obtained, gas and blood volume fractions within three gravitational regions calculated and normalized to lung tissue mass (normalized gas volume and normalized blood volume, respectively). Ventilatory conditions were grouped based upon the fractional atelectatic mass in expiration (< 20%, 20-40%, and ≥ 40%). Tidal recruitment/derecruitment with fractional atelectatic mass in expiration greater than or equal to 40% was less than 7% of lung mass. In this group, inspiration-related increase in normalized gas volume was greater in the nondependent (818 µL/g [95% CI, 729-908 µL/g]) than the dependent region (149 µL/g [120-178 µL/g]). Normalized blood volume decreased in inspiration in the nondependent region (29 µL/g [12-46 µL/g]) and increased in the dependent region (39 µL/g [30-48 µL/g]). Inspiration-related changes in normalized gas volume and normalized blood volume were negatively correlated in fractional atelectatic mass in expiration greater than or equal to 40% and 20-40% groups (r = 0.56 and 0.40), but not in fractional atelectatic mass in expiration less than 20% group (r = 0.01). Both the increase in normalized blood volume in the dependent region and fractional atelectatic mass in expiration negatively correlated with PaO2/FIO2 ratio (ρ = -0.77 and -0.93, respectively).

Conclusions: In experimental atelectasis with minimal tidal recruitment/derecruitment, mechanical inspiratory breaths redistributed blood volume away from well-ventilated areas, worsening PaO2/FIO2.

Figure 1.

Methodology. A, Schematic of dual-source CT scanner gantry showing two separate x-ray sources at 90 degree offsets with example photon energies density distributions demonstrating minimal overlap between the two (140 kVp spectrum has low-energy photons attenuated by a 0.4 mm tin filter). Points A–D represent examples of imaged objects with distinct compositions. Point A is 100% gas and is reliably interpreted as –1,000 Hounsfield units (HU) at both energy levels. Point B, however, is composed of three different materials but is interpreted as 58 HU at 140 kVp, the same as a voxel comprising 100% soft tissue (point D). When points B and D are imaged at 80 kVp, they have different CT densities (78 and 62 HU), thus the materials can be differentiated. A similar argument exists for point C. B, In general, after plotting the CT densities of all voxels in an image (here one of the volume scans used for this paper), various distributions can be seen. Point E—100% gas; F—100% soft tissue; G—100% iodinated blood; H—CT scanner table; I—bone. All voxels containing a mix of purely gas and soft tissue fall along the identity line; however, if iodine is added, they are displaced from this line, thus allowing the composition of the voxel to be identified. C, Normalization of dynamic dual-energy CT (DECT) gas and iodinated blood volumes to lung tissue mass. Individual frames were scaled up to the size of the whole lung using a scale factor defined as the ratio of the entire thorax to the slice and then divided by the mass of soft tissue in the whole lung. Whole lung gas volumes were used to calculate fractional atelectatic mass in expiration, cyclical recruitment/derecruitment (R/D), and overdistended volume.

Figure 2.

Example source and post-processed images of a single juxtadiaphragmatic slice at positive end-expiratory pressure 5 cm H₂O of pig’s thorax during iodine infusion using the dual-energy CT (DECT) algorithm. A, Composite source images representing a 30:70 merge of 80 kVp and 140 kVp images displayed using standard CT lung windows. B, Results of the DECT three-material differentiation algorithm for gas (blue), soft tissue (green), and iodinated blood (red) volume fractions. C, The DECT images following segmentation to include only lung parenchyma with the three gravitational regions of interest displayed. Typical expiration and inspiration images are shown in each case. A gravitational effect was seen within the slice with soft tissue and iodinated blood concentrated toward the dependent regions, with a reduction in volume fractions of these materials in inspiration.

Figure 3.

Effects of inspiration on the volume fractions and normalized volumes of gas and iodinated blood within the juxtadiaphragmatic slice over the course of two respiratory cycles. Results are presented for the three different gravitational regions of the studied slice and grouped by fractional atelectatic mass of the lung in expiration (FAM_exp). Airway pressure traces are provided for comparison, and gray background denotes inspiration. In all regions and all FAM_exp groups gas volume fraction and normalized gas volume increased (p ≤ 0.01) and blood volume fraction decreased (p < 0.005) during inspiration. The effects of inspiration on normalized blood volume were most pronounced in the FAM_exp greater than or equal to 40% group, with normalized blood volume decreasing in the middle and nondependent regions and increasing in the dependent region. Points represent mean and sd.

Figure 4.

Absolute and relative changes in expiratory normalized gas (V_N) and blood volumes (QN). V_N (A) and Q_N (B) within each region, and fractional expiratory mass of the lung in expiration (FAM_exp) grouping. C, Effects of an inspiratory breath upon V_N. In the higher FAM_exp groups there is relatively less ventilation occurring in the dependent regions. D, Effects of an inspiratory breath upon Q_N. Minimal change was seen in normalized blood volume in the FAM_exp less than 20% group, however, in the other conditions the normalized blood volume in the dependent region increased and those in the others decreased with inspiration. Points represent mean and either sd (A and B) or 95% CI of change (C and D).

Figure 5.

Relationship between the inspiratory change in normalized gas and blood volumes dependent upon fraction of the mass of the entire lung that was atelectatic in expiration (FAM_exp). For FAM_exp less than 20% minimal relationship was seen; however, within the other two groups there was a clear negative relationship: those regions with the least ventilation received an increase in blood volume and those with the most ventilation a decrease, suggestive of an inspiration-related redistribution that worsened ventilation-perfusion matching.

Figure 6.

Pao₂/Fio₂ (P/F) values associated with atelectasis and blood volume redistribution. Effect of atelectasis (A) and intra-tidal normalized blood volume redistribution toward the dependent region (B) upon P/F ratio. P/F ratio was negatively correlated with both measures in a nonlinear fashion (Spearman ρ = –0.93 and –0.77, respectively) and the log-transform of P/F ratio was linearly related to atelectasis (r² = 0.87). Box-and-whisker plots represent median, interquartile range and range for the three different fractional atelectatic mass in expiration (FAM_exp) groups studied (A) and between those conditions that demonstrated either an inspiration-related reduction or increase in blood volume in the dependent region (B).