Liver dysfunction after lung recruitment manoeuvres during pressure-controlled ventilation in experimental acute respiratory distress

Abstract

Introduction: Consequences of lung recruitment with prolonged high positive end-expiratory pressure (PEEP) ventilation for liver function are unclear. We therefore investigated liver dysfunction during two different ventilation treatment regimens of experimental acute respiratory distress syndrome.

Methods: Sixteen anaesthetised juvenile pietrain pigs were ventilated in the pressure-controlled mode (PCV) with an inspiratory fraction of oxygen (FiO2) of 1.0, a respiratory frequency of 30 per minute, a tidal volume of 6 ml/kg, and a PEEP of 5 cm H2O. After lung injury was induced by repeated pulmonary lavage with normal saline, animals were randomly assigned into two groups (n = 8 each) for a 24-hour trial: PCV (unchanged ventilation) and PCV with recruitment (PCV+R) (starting with a sustained inflation of 50 cm H2O for 1 minute, the ventilation was continued while increasing PEEP in increments of 3 cm H2O every 15 minutes as long as arterial oxygen tension [PaO2] improved). After recruitment, FiO2 was reduced to 0.4 and the PEEP was lowered every 15 minutes until PaO2 decreased to 12.0 to 14.7 kPa (90 to 110 torr). Serum levels of hyaluronic acid (HA), routine liver serum markers, and plasma disappearance rate of indocyanine green (ICG) were tested before and after lung injury, and 6 and 18 hours after randomisation. Liver serum markers were also tested at 24 hours. Paraffin sections of liver tissue stained by haematoxylin and eosin were made after euthanisation.

Results: The PCV+R group exhibited more polymorphonuclear neutrophils and lymphocytes in the liver sinusoids: median score (interquartile range) of 1.5 (1.4 to 1.5) compared to 0.9 (0.7 to 1.1) (p = 0.01). Elevation of bilirubin, aspartate aminotransferase, and lactate dehydrogenase was more prominent in the PCV+R group. Plasma disappearance rate of ICG indicated no liver dysfunction. HA levels in the PCV+R group gradually increased and were significantly higher (p < 0.001) at 6 and 18 hours with 59 (57 to 64) and 75 (66 to 84) ng/ml, respectively, than in the PCV group with 34 (32 to 48) and 41 (38 to 42) ng/ml, respectively.

Conclusion: The PCV+R group showed a more prominent inflammatory reaction in their liver sinusoids accompanied by increased serum levels of liver enzymes and HA. Therefore, recruitment with higher PEEP levels for treatment of respiratory failure might lead to liver dysfunction.

Figure 1

Mean airway pressure during the trial. After the induction of acute lung injury (ALI), a recruitment manoeuvre was performed in the PCV+R group by sustained inflation and stepwise increase of positive end-expiratory pressure (PEEP) by 3 cm H₂O every 15 minutes. Recruitment was followed by stepwise reduction of PEEP according to target arterial oxygen tension. In the PCV group, level of PEEP remained at 5 cm H₂O. Median values of the groups are shown. PCV, pressure-controlled ventilation; PCV+R, pressure-controlled ventilation with recruitment manoeuvre.

Figure 2

Hyaluronic acid serum concentration. Data are presented as the median with 25% to 75% interquartile range. Mann-Whitney rank sum test: #, p < 0.05 versus PCV+R. Friedman repeated measures analysis of variance on ranks with all pairwise multiple comparison procedures (Student-Newman-Keuls method): §, versus T_baseline; *, versus T_ALI; &, versus six hours (p < 0.05). PCV, pressure-controlled ventilation; PCV+R, pressure-controlled ventilation with recruitment manoeuvre; T_{6 h}, time point 6 hours after randomisation; T_{18 h}, time point 18 hours after randomisation; T_ALI, time point after lung injury; T_baseline, baseline time point.

Figure 3

Histologic injury score of liver tissue. Scores were calculated as follows: injury not present (grade 0), less than or equal to 20% of the lobulus (grade 1), more than 20% to less than or equal to 50% (grade 2), or more than 50% (grade 3). The mean score for every animal was calculated out of 10 evaluations. Data are presented as the median with 25% to 75% interquartile range. Mann-Whitney rank sum test: #, p < 0.05 versus PCV+R (p < 0.05). H, haemorrhage; N, necrosis; PCV, pressure-controlled ventilation; PCV+R, pressure-controlled ventilation with recruitment manoeuvre; Sept. I., septal inflammation; Sinus. I., sinusoidal inflammation.

Figure 4

Accumulation of inflammatory cells in liver sinusoids. Representative centrolobular parts of liver tissue sections stained with haematoxylin and eosin are shown as low-power fields (a,b) and high-power fields (c,d) of the same area (optical magnification of microscope × 10 and × 40). (a,c) Animal from the PCV group. Few inflammatory cells are shown. (b,d) Animal from the PCV+R group. Infiltration of polymorphonuclear neutrophils and lymphocytes in the sinusoidal area of the liver is shown. PCV, pressure-controlled ventilation; PCV+R, pressure-controlled ventilation with recruitment manoeuvre.