Is there a place for pressure-support ventilation and high positive end-expiratory pressure combined to alpha-2 agonists early in severe diffuse acute respiratory distress syndrome?  C. Pichot, F. Petitjeans, M. Ghignone, L. Quintin  Medical Hypotheses  Volume 80, Issue 6, Pages 732-737 (June 2013) DOI: 10.1016/j.mehy.2013.02.023 Copyright © 2013 Elsevier Ltd Terms and Conditions

Fig. 1 Pressure–volume (P–V) curve of a moderately diseased ARDS lung. Note on the incremental limb of the P–V curve, a lower (LIP=Pflex) and an upper inflection (UIP) point. In sea mammals, Vt is close to 90% of vital capacity, to withstand prolonged apneas. By contrast, in humans, a transpulmonary pressure=15cm H2O subjects the lung to two-thirds of its total lung capacity and generates a Vt≈2500ml [27]. Human Vt is close to 10–20% of vital capacity, which fits with the poor tolerance to overdistension. In healthy lung, the closing volume is lower than FRC. Airway closure occurs during expiration. The closing volume increases above FRC in the supine position, pregnancy, obesity, ageing, following abdominal surgery, upon heart failure. Upon ARDS, hypoxia is explained by airway closure leading to intrapulmonary shunt. A correlation is observed between PaO2 and FRC (Rouby, 2000). The FRC is reduced by −58% upon early ARDS (−84% in the lower lobes) (Puybasset, 2000): the lung functionally “shrinks” (“baby lung”). In the zone of derecruitment-atelectasis, lung injury develops through the direct trauma of repeated closure-reexpansion of airways and alveoli (inflammation), inhibition of surfactant, effects of local hypoxemia. Atelectrauma is secondary to the repetitive opening upon inspiration and closing of alveoli at end-expiration when PEEP levels are inadequate to prevent end-expiratory derecruitment. Lung recruitment is an inspiratory phenomenon (opening pressure at LIP-Pflex) e.g. upon recruitment maneuvers/high Ppeak/Pplat. By contrast, PEEP increases FRC, prevents expiratory derecruitment (closing pressure on the expiratory limb of the P–V curve), translocates edema from alveoli to the interstitial perivascular space and improves the VA/Q ratio. By maintaining open alveoli, which were previously closed (PEEP>closing pressure), tidal volume is distributed to more alveoli: compliance increases. Ppeak and Pplat decrease. Above UIP, over-distention occurs from mechanical disruption (volu- and baro-trauma: pneumothorax/, pulmonary overinflation). With the equation of motion of the respiratory system: Paw+Pmuscles=PEEPtot+Pres+Pel (Paw: airway pressure generated by the respirator; Pmuscles: pressure generated by the respiratory muscles of the patient; Pres: pressure linked to resistance of the airway=R×V with R: resistance of the airway, V: airflow rate; Pel: pressure linked to the elastance of the lung=E×Vt with EL: elastance (1/static compliance)) then, Vt=Pel/EL. With PS=10, Palv=8, Pres=2, Ppl=−15 and EL=30 then Pel=23 and Vt=23/30=766ml. Then, above closing volume, low level of PS (5–10cm H2O) are needed to generate a Vt (below 400–500ml) compatible with permissive hypercapnia on the one hand, and little or no volu-trauma on the other hand. This explains the low PS observed with our technique, which in turn allows one to use high PEEP. Schematically, the lung may be viewed as a kid’s balloon to be inflated above a given volume (opening volume at opening pressure) for once with large sheer forces (e.g. recruitment maneuvers or at Ppeak). Once inflated, the balloon is to be kept inflated (high PEEP above closing volume) at all times (i.e. end-expiration) to suppress repetitive opening-closing. Lastly the balloon is to be oxygenated with minimal sheer forces (here preferably low PS under permissive hypercapnia), to suppress overdistension (volutrauma). The right ventricle should be closely monitored. Modified from Froese, Crit Care Med 1997, 25, 906-8. Medical Hypotheses 2013 80, 732-737DOI: (10.1016/j.mehy.2013.02.023) Copyright © 2013 Elsevier Ltd Terms and Conditions