Computed tomography assessment of exogenous surfactant-induced lung reaeration in patients with acute lung injury

Abstract

Introduction: Previous randomized trials failed to demonstrate a decrease in mortality of patients with acute lung injury treated by exogenous surfactant. The aim of this prospective randomized study was to evaluate the effects of exogenous porcine-derived surfactant on pulmonary reaeration and lung tissue in patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS).

Methods: Twenty patients with ALI/ARDS were studied (10 treated by surfactant and 10 controls) in whom a spiral thoracic computed tomography scan was acquired before (baseline), 39 hours and 7 days after the first surfactant administration. In the surfactant group, 3 doses of porcine-derived lung surfactant (200 mg/kg/dose) were instilled in both lungs at 0, 12 and 36 hours. Each instillation was followed by recruitment maneuvers. Gas and tissue volumes were measured separately in poorly/nonaerated and normally aerated lung areas before and seven days after the first surfactant administration. Surfactant-induced lung reaeration was defined as an increase in gas volume in poorly/non-aerated lung areas between day seven and baseline compared to the control group.

Results: At day seven, surfactant induced a significant increase in volume of gas in poorly/non-aerated lung areas (320 ± 125 ml versus 135 ± 161 ml in controls, P = 0.01) and a significant increase in volume of tissue in normally aerated lung areas (189 ± 179 ml versus -15 ± 105 ml in controls, P < 0.01). PaO2/FiO2 ratio was not different between the surfactant treated group and control group after surfactant replacement.

Conclusions: Intratracheal surfactant replacement induces a significant and prolonged lung reaeration. It also induces a significant increase in lung tissue in normally aerated lung areas, whose mechanisms remain to be elucidated.

Trial registration: NCT00742482.

Figures

Figure 1

Representative CT sections of upper and lower lobes obtained at baseline and day 7 in a patient with acute respiratory distress syndrome. Computed tomography (CT) sections at baseline and day 7 are at the same lung region as attested by the anatomical landmarks present on the rough images at baseline and day 7 (aortic arch and vascular divisions for upper lobe CT sections and vascular divisions for the lower lobe CT sections). As previously described [18], poorly and nonaerated lung areas of right and left upper and lower lobes are manually delineated (dashed line) at baseline (before HL-10 administration) with the aid of the software Lungview) that identifies poorly and nonaerated lung areas in light gray and red, respectively. Delineation performed at baseline is manually 'transposed' to the CT section corresponding to the same anatomical level obtained at day 7. Surfactant-induced lung reaeration is defined as the increase in gas volume within the delineated zone between day 7 and baseline. The same process is repeated on each CT section in order to assess overall surfactant-induced lung reaeration.

Figure 2

PaO2/FiO2 ratio at baseline, 39 hours after baseline (H39) and day 7 in control (open circles) and surfactant groups (closed circles) of patients with acute lung injury/acute respiratory distress syndrome. FiO2, fraction of inspired oxygen; PaO2, partial pressure of arterial oxygen.

Figure 3

Volumes of gas and tissue at baseline before HL-10 instillation (upper part of the figure) and changes in volume of gas and tissue between H39 (within three hours following the third bolus of HL-10) and baseline (lower part of the figure). Results shown in right upper and middle lobes (RUL), left upper lobe (LUL), right lower lobe (RLL) and left lower lobe (LLL) in patients with acute lung injury/acute respiratory distress syndrome instilled with 200 mg/kg of HL-10. Comparisons were performed by Friedman repeated measures analysis of variance on ranks followed by a Tukey test. P values above the horizontal brackets indicate significant difference between RUL, LUL, RLL and LLL using Friedman repeated measures analysis of variance.* P < 0.05 versus RUL, § P < 0.05 versus LUL.

Figure 4

Computerized tomography assessment of total gas and tissue volumes at baseline, 39 hours after baseline (H39) and day 7, in control (open circles) and surfactant groups of patients (closed circles).

Figure 5

Individual and mean changes in volume of gas and tissue in poorly/nonaerated lung regions (upper part of the figure) and normally aerated lung regions (lower part of the figure). Volume changes were measured on computed tomography scans acquired at baseline and seven days in patients who received either usual care (control, open circles) or usual care plus intratracheal porcine-derived surfactant (HL-10, closed circles). In the surfactant group, each patient is identified by a specific symbol.