Computer simulation clarifies mechanisms of carbon dioxide clearance during apnoea.

BACKGROUND: Apnoeic oxygenation can come close to matching the oxygen demands of the apnoeic patient but does not facilitate carbon dioxide (CO2) elimination, potentially resulting in dangerous hypercapnia. Numerous studies have shown that high-flow nasal oxygen administration prevents hypoxaemia, and appears to reduce the rate of increase of arterial CO2 partial pressure (PaCO2), but evidence is lacking to explain these effects. METHODS: We extended a high-fidelity computational simulation of cardiopulmonary physiology to include modules allowing variable effects of: (a) cardiogenic oscillations affecting intrathoracic gas spaces, (b) gas mixing within the anatomical dead space, (c) insufflation into the trachea or above the glottis, and (d) pharyngeal pressure oscillation. We validated this model by reproducing the methods and results of five clinical studies on apnoeic oxygenation. RESULTS: Simulated outputs best matched clinical data for model selection of parameters reflecting: (a) significant effects of cardiogenic oscillations on alveoli, both in terms of strength of the effect (4.5 cm H2O) and percentage of alveoli affected (60%), (b) augmented gas mixing within the anatomical dead space, and (c) pharyngeal pressure oscillations between 0 and 2 cm H2O at 70 Hz. CONCLUSIONS: Cardiogenic oscillations, dead space gas mixing, and micro-ventilation induced by pharyngeal pressure variations appear to be important mechanisms that combine to facilitate the clearance of CO2 during apnoea. Evolution of high-flow oxygen insufflation devices should take advantage of these insights, potentially improving apnoeic gas exchange.

High PEEP in acute respiratory distress syndrome: quantitative evaluation between improved arterial oxygenation and decreased oxygen delivery.

BACKGROUND: Positive end-expiratory pressure (PEEP) is widely used to improve oxygenation and prevent alveolar collapse in mechanically ventilated patients with the acute respiratory distress syndrome (ARDS). Although PEEP improves arterial oxygenation predictably, high-PEEP strategies have demonstrated equivocal improvements in ARDS-related mortality. The effect of PEEP on tissue oxygen delivery is poorly understood and is difficult to quantify or investigate in the clinical environment. METHODS: We investigated the effects of PEEP on tissue oxygen delivery in ARDS using a new, high-fidelity, computational model with highly integrated respiratory and cardiovascular systems. The model was configured to replicate published clinical trial data on the responses of 12 individual ARDS patients to changes in PEEP. These virtual patients were subjected to increasing PEEP levels during a lung-protective ventilation strategy (0-20 cm H2O). Measured variables included arterial oxygenation, cardiac output, peripheral oxygen delivery, and alveolar strain. RESULTS: As PEEP increased, tissue oxygen delivery decreased in all subjects (mean reduction of 25% at 20 cm H2O PEEP), despite an increase in arterial oxygen tension (mean increase 6.7 kPa at 20 cm H2O PEEP). Changes in arterial oxygenation and tissue oxygen delivery differed between subjects but showed a consistent pattern. Static and dynamic alveolar strain decreased in all patients as PEEP increased. CONCLUSIONS: Incremental PEEP in ARDS appears to protect alveoli and improve arterial oxygenation, but also appears to impair tissue oxygen delivery significantly because of reduced cardiac output. We propose that this trade-off may explain the poor improvements in mortality associated with high-PEEP ventilation strategies.

Apnoeic oxygenation in pregnancy: a modelling investigation.

Recent studies have shown that nasal oxygen delivery can prolong the time to desaturation during apnoea in the non-pregnant population. We investigated the benefits of apnoeic oxygenation during rapid sequence induction in the obstetric population using computational modelling. We used the Nottingham Physiology Simulator, and pre-oxygenated seven models of pregnancy for 3 min using Fi O2 1.0, before inducing apnoea. We found that increasing Fi O2 at the open glottis increased the time to desaturation, extending the time taken for Sa O2 to reach 40% from 4.5 min to 58 min in the average parturient model (not in labour). Our study suggests that a small increase in time to desaturation could be achieved at Fi O2 0.4-0.6, which could be delivered by standard nasal cannulae. The greatest increases in time to desaturation were seen at Fi O2 1.0, which could be delivered by high-flow nasal cannulae under ideal conditions.

The effect of prone positioning with surgical bolsters on liver blood flow in healthy volunteers.

This study sought to identify changes in hepatic flood flow and cardiac output during prone positioning on surgical bolsters in awake volunteers, and was prompted by a local incident of significant hepatic dysfunction following surgery in the prone position. Cardiac output was determined using the non-invasive Peñáz technique, and plasma disappearance rate of indocyanine green (ICG-PDR) was measured as a surrogate maker for hepatic blood flow along with serum hepatic enzyme assays. Measurements were made after one hour in supine, prone and returned supine positions. Ten volunteers completed the study. There were significant changes in the disappearance rate of indocyanine green, which decreased this from mean (SD) 31.1 (9.70) supine to 19.6 (4.37)%.min prone, respectively (p = 0.02), increasing on return to the supine position to 24.6 (5.54)%.min (p = 0.019). Cardiac output was also significantly reduced when changing from the supine to the prone position, from mean (SD) 4.7 (1.0 to 3.5 (1.1) (l.min(-1) ), respectively (p = 0.002). We demonstrated an acute and reversible change in both hepatocellular function and cardiac output associated with the prone position.