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Airway pressure release ventilation (APRV) is a ventilatory mode which allows unrestrictedspontaneous breathing (SB) throughout the ventilatory cycle. If SB is insufficient, mechanicalventilatory support is achieved by brief periodic decreases of the airway pressure below the CPAPlevel. Thus, APRV is a combination of pressure-controlled inverse ratio ventilation (PC-IRV) andCPAP-breathing. However, lung collapse may be provoked during the short expiratory time intervals,and the desirable proportion of SB and mechanical ventilation is not known. The aim of the study wastherefore to systematically investigate the different components of APRV which are PC-IRV and SBin regard to gas exchange, haemodynamics and lung collapse. Gas exchange, hemodynamics and the time course of lung collapse and recruitment were comparedin oleic acid-, lavage- and endotoxin-induced lung injury in pigs. Oleic acid injection caused a severelung damage with the most unstable lungs. Thus, we choose the oleic acid model to investigate APRVin a worst case scenario. During expiration, lung collapse could only be avoided by very short expiration times ≤ 0.6 seconds or by high PEEP levels ≥ 20 cm H2O or more. Recruitment occurred mainly within 1.4 seconds of inspiration, but airway pressures up to 40 cm H2O did not open up the lungs completely.Gas exchange was better when the lungs were stabilised by PEEP compared to the use of shortexpiration times, and aeration was more homogenous with PEEP. CPAP was superior to partialventilatory support using APRV. This may be due to beneficial effects of spontaneous breathing ongas exchange breathing per se, but also that APRV may allow rapid lung collapse during the phases ofairway pressure release below the CPAP level. Therefore, the amount of mechanical ventilatorysupport using the APRV mode should be kept at the lowest possible level, that is sufficient for thepatient to cope with the work of breathing and to avoid respiratory muscle fatigue. In conclusion

Airway pressure release ventilation (APRV) is a promising, unconventional mode of ventilation for the treatment of various respiratory diseases, including acute respiratory distress syndrome (ARDS). However, despite increasing global use and reported advantages of APRV over other modes, definitive conclusions cannot be drawn due to several concerns. First, the major confusion between APRV and other, similar modes, such as bi-phasic positive airway pressure (BIPAP). Second, clinical and methodological heterogeneity among published studies of APRV are understandably extensive, which contributes to outcome variability. Third, the absence of consensus on a standard protocol with clear rationale for the settings. This thesis provides an overview of the spectrum of ventilator settings that may be designated as APRV, summarises the research and clinical use status of APRV, exemplifies the need to clarify the characteristics that comprise the mode, and to assure reports of APRV use, from case reports through RCTs, including adequate data for a proper assessment. It encourages continued publication of observational as well as experimental clinical trial data, and discusses the feasibility of analysis strategies that may expand the information available from small patient samples. It also presents an unpublished, comprehensive, multifaceted clinical practice protocol (Al-ahmad protocol) for the use of APRV. Using the Al-ahmad protocol, four studies were conducted on non-spontaneously breathing patients who had ARDS (arising from a variety of pathologies). One study used a validated physiological simulator called integrated cardiopulmonary models (ICPMs) while the other three, were prospective cohort observational studies on real patients. The first study evaluated patients’ responses to changes in inspiratory pressure during conventional ventilation (CV) and APRV modes, using ICPMs vs. a real patient. The second study compared partial pressure of carbon dioxide (PaCO2) at any