Positive end-expiratory pressure and tidal volume during initial ventilation of preterm lambs

Abstract

Positive end-expiratory pressure (PEEP) protects the lung from injury during sustained ventilation, but its role in protecting the lung from injury during the initiation of ventilation in the delivery room is not established. We aimed to evaluate whether PEEP and/or tidal volume (VT) within the first 15-min of ventilation are protective against lung injury. Operatively delivered preterm lambs (133 +/- 1 d gestation) were randomly assigned to unventilated controls or to one of four 15 min ventilation interventions: 1) VT15 mL/kg, PEEP 0 cm H2O; 2) VT15 mL/kg, PEEP 5 cm H2O; 3) VT8 mL/kg, PEEP 0 cm H2O; and 4) VT8 mL/kg, PEEP 5 cm H2O. Each group was subsequently ventilated with VT 10 mL/kg, PEEP 5 cm H2O for 1 h 45 min. Lung function was assessed and measurements of lung injury were evaluated postmortem. After the 15 min ventilation maneuver, the VT15 groups were hypocarbic, had higher oxygenation, and required lower pressures than the VT8 groups; no consistent effect of PEEP was found. Markers of lung injury were significantly elevated in all ventilation groups compared with unventilated controls; no effect of PEEP was found. Ventilation resulted in localization of IL-6 to the small airways. Initial ventilation of preterm lambs with PEEP and/or VT of 8 mL/kg did not prevent an inflammatory injury to the lung.

Figure 1

PaCO₂ (A) and Oxygenation Index (OI), B) in ventilation groups following the 15 min initial ventilation period up to 90 min. Values at 120 min are not included because the lambs were ventilated with 100% oxygen to facilitate lung collapse. ▼; V_T 8 PEEP 0, △: V_T 8 PEEP 5, ●: V_T 15 PEEP 5, ○: V_T 15 PEEP 0. Groups receiving V_T of 15 mL/kg during initial ventilation had lower PaCO₂ prior to normalization after 30 min, and a lower oxygenation index throughout subsequent ventilation, compared to groups that received V_T of 8 mL/kg. Group means ± SEM shown. * p<0.05 V_T15 mL/kg vs. V_T8 mL/kg. ^¶ p = 0.067 V_T15 mL/kg vs. V_T8 mL/kg.

Figure 2

Tidal volume V_T (A) and Peak inspiratory pressure (B) in ventilatory groups after the initial ventilation period. ▼: V_T 8 PEEP 0, △: V_T 8 PEEP 5, ●: V_T 15 PEEP 5, ○: V_T 15 PEEP 0. * p<0.05 V_T 15 mL/kg vs. V_T 8 mL/kg. Groups receiving high V_T during the initial 15 min ventilation period required lower ventilatory pressures to maintain a V_T of 8 mL/kg during subsequent ventilation.

Figure 3

Deflation pressure-volume curves. ▼: V_T 8 PEEP 0, △: V_T 8 PEEP 5, ●: V_T 15 PEEP 5, ○: V_T 15 PEEP 0. Volumes at 15, 20 and 40 cmH₂O were similar between ventilation groups. Group means ± SEM shown.

Figure 4

Total protein (A), IL-1β (B) IL-6 (C) and IL-8 (D) mRNA from lung tissue in lambs receiving V_T 15 mL/kg (□) or V_T 8 mL/kg () receiving either 0 cmH₂O or 5 cmH₂O PEEP during the initial resuscitation period; expressed as fold increase relative to control (non-ventilated) lambs (■). Group means ± SEM shown. *p<0.05 vs. controls.

Figure 5

Localisation of IL-6 mRNA expression in control (A-B), a lamb ventilated with V_T 15 mL/kg, PEEP 0 cmH₂O (C), and a lamb ventilated with V_T 8 mL/kg, PEEP 5 cmH₂O (D). IL-6 expression is depicted in black silver grains. No IL-6 expression was detected in control lambs (n=2-3/group). Mechanical ventilation robustly induced IL-6 expression in the terminal bronchiolar/alveolar duct epithelium (bold arrows; see panel C), inflammatory cells (open arrowhead) (panels C&D) and bronchial smooth muscle (dark arrowhead; see panel D). Note the absence of IL-6 expression in the large bronchial epithelium (open arrow in panel D). (Bar denotes 50μm, Br=Bronchus). F) Qualitative assessment of mean score of intensity of IL-6 expression. * p<0.05; 5 cmH₂O PEEP vs 0 cmH₂O PEEP. All ventilation groups have significantly more IL-6 staining than unventilated controls.