Abstract
BackgroundClinical trials have, so far, failed to establish clear beneficial outcomes of recruitment maneuvers (RMs) on patient mortality in acute respiratory distress syndrome (ARDS), and the effects of RMs on the cardiovascular system remain poorly understood.MethodsA computational model with highly integrated pulmonary and cardiovascular systems was configured to replicate static and dynamic cardio-pulmonary data from clinical trials. Recruitment maneuvers (RMs) were executed in 23 individual in-silico patients with varying levels of ARDS severity and initial cardiac output. Multiple clinical variables were recorded and analyzed, including arterial oxygenation, cardiac output, peripheral oxygen delivery and alveolar strain.ResultsThe maximal recruitment strategy (MRS) maneuver, which implements gradual increments of positive end expiratory pressure (PEEP) followed by PEEP titration, produced improvements in PF ratio, carbon dioxide elimination and dynamic strain in all 23 in-silico patients considered. Reduced cardiac output in the moderate and mild in silico ARDS patients produced significant drops in oxygen delivery during the RM (average decrease of 423 ml min−1 and 526 ml min−1, respectively). In the in-silico patients with severe ARDS, however, significantly improved gas-exchange led to an average increase of 89 ml min−1 in oxygen delivery during the RM, despite a simultaneous fall in cardiac output of more than 3 l min−1 on average. Post RM increases in oxygen delivery were observed only for the in silico patients with severe ARDS. In patients with high baseline cardiac outputs (>6.5 l min−1), oxygen delivery never fell below 700 ml min−1.ConclusionsOur results support the hypothesis that patients with severe ARDS and significant numbers of alveolar units available for recruitment may benefit more from RMs. Our results also indicate that a higher than normal initial cardiac output may provide protection against the potentially negative effects of high intrathoracic pressures associated with RMs on cardiac function. Results from in silico patients with mild or moderate ARDS suggest that the detrimental effects of RMs on cardiac output can potentially outweigh the positive effects of alveolar recruitment on oxygenation, resulting in overall reductions in tissue oxygen delivery.
Highlights
Clinical trials have, so far, failed to establish clear beneficial outcomes of recruitment maneuvers (RMs) on patient mortality in acute respiratory distress syndrome (ARDS), and the effects of Recruitment maneuver (RM) on the cardiovascular system remain poorly understood
List of Abbreviations CO cardiac output, FiO2 fraction of O2 in inspired gas, Vt tidal volume, VR ventilator rate, positive end-expiratory pressure (PEEP) positive end expiratory pressure, Inspiratory to expiratory ratio (IE) inspiratory to expiratory ratio, Respiratory quotient (RQ) respiratory quotient, Oxygen consumption [ml min−1] (VO2) oxygen consumption, TOP threshold opening pressure, S alveolar stiffness factor, Pext extrinsic pressure, Haemoglobin content in blood [gm l−1] (Hb) hemoglobin in blood, PaO2 arterial oxygen tension, PaCO2 arterial carbon dioxide tension, Partial pressure of mixed venous oxygen [kpa] (PvO2) mixed venous oxygen tension, shunt fraction aOptimization methodology and parameter ranges given in Additional file 1
Model outputs accurately reproduce clinical datasets The results of matching the model to data from [25,26,27] on 3 ARDS patients of varying ARDS severity and varying cardiac output are given in Table 1 and Fig. 2, and the results of the model matching to the dataset from [5] on 20 patients stratified by ARDS severity are shown in Table 2 and Fig. 3
Summary
Failed to establish clear beneficial outcomes of recruitment maneuvers (RMs) on patient mortality in acute respiratory distress syndrome (ARDS), and the effects of RMs on the cardiovascular system remain poorly understood. Increase in PIT reduces the pressure gradient between the systemic venous pressure and the RV diastolic pressure, reducing venous return, decreasing RV filling and decreasing stroke volume (SV) and decreasing inflow to the left ventricle [10]. This passive relationship between RV and LV is compounded by the direct effects of raised PIT [9] on the ventricular walls (splinting) as well as the potential for intraventricular septum shift (ventricular interdependence) [11]. Evaluating the relative effectiveness of different RMs in clinical studies is extremely challenging, since it is difficult to isolate the effects of ventilatory strategies, and because different RMs cannot be applied to the same patient simultaneously
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