ABSTRACT
BACKGROUND: Acute respiratory distress syndrome causes a heterogeneous lung injury with normal and acutely injured lung tissue in the same lung. Improperly adjusted mechanical ventilation can exacerbate ARDS causing a secondary ventilator-induced lung injury (VILI). We hypothesized that a peak airway pressure of 40 cmH2O (static strain) alone would not cause additional injury in either the normal or acutely injured lung tissue unless combined with high tidal volume (dynamic strain). METHODS: Pigs were anesthetized, and heterogeneous acute lung injury (ALI) was created by Tween instillation via a bronchoscope to both diaphragmatic lung lobes. Tissue in all other lobes was normal. Airway pressure release ventilation was used to precisely regulate time and pressure at both inspiration and expiration. Animals were separated into two groups: (1) over-distension + high dynamic strain (OD + HDS, n = 6) and (2) over-distension + low dynamic strain (OD + LDS, n = 6). OD was caused by setting the inspiratory pressure at 40 cmH2O and dynamic strain was modified by changing the expiratory duration, which varied the tidal volume. Animals were ventilated for 6 h recording hemodynamics, lung function, and inflammatory mediators followed by an extensive necropsy. RESULTS: In normal tissue (NT), OD + LDS caused minimal histologic damage and a significant reduction in BALF total protein (p < 0.05) and MMP-9 activity (p < 0.05), as compared with OD + HDS. In acutely injured tissue (ALIT), OD + LDS resulted in reduced histologic injury and pulmonary edema (p < 0.05), as compared with OD + HDS. CONCLUSIONS: Both NT and ALIT are resistant to VILI caused by OD alone, but when combined with a HDS, significant tissue injury develops.
ABSTRACT
PURPOSE: Preterm infants are prone to respiratory distress syndrome (RDS), with severe cases requiring mechanical ventilation for support. However, there are no clear guidelines regarding the optimal ventilation strategy. We hypothesized that airway pressure release ventilation (APRV) would mitigate lung injury in a preterm porcine neonatal model. METHODS: Preterm piglets were delivered on gestational day 98 (85% of 115day term), instrumented, and randomized to volume guarantee (VG; n=10) with low tidal volumes (5.5cm3kg-1) and PEEP 4cmH2O or APRV (n=10) with initial ventilator settings: PHigh 18cmH2O, PLow 0cmH2O, THigh 1.30s, TLow 0.15s. Ventilator setting changes were made in response to clinical parameters in both groups. Animals were monitored continuously for 24hours. RESULTS: The mortality rates between the two groups were not significantly different (p>0.05). The VG group had relatively increased oxygen requirements (FiO2 50%±9%) compared with the APRV group (FiO2 28%±5%; p>0.05) and a decrease in PaO2/FiO2 ratio (VG 162±33mmHg; APRV 251±45mmHg; p<0.05). The compliance of the VG group (0.51±0.07L·cmH2O-1) was significantly less than the APRV group (0.90±0.06L·cmH2O-1; p<0.05). CONCLUSION: This study demonstrates that APRV improves oxygenation and compliance as compared with VG. This preliminary work suggests further study into the clinical uses of APRV in the neonate is warranted. LEVEL OF EVIDENCE: Not Applicable (Basic Science Animal Study).
