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Background: Optimal respiratory support in early COVID-19 pneumonia is controversial and remains unclear. Using computational modelling, we examined whether lung injury might be exacerbated in early COVID-19 by assessing the impact of conventional oxygen therapy (COT), high-flow nasal oxygen therapy (HFNOT), continuous positive airway pressure (CPAP), and noninvasive ventilation (NIV).Methods: Using an established multi-compartmental cardiopulmonary simulator, we first modelled COT at a fixed FiO2 (0.6) with elevated respiratory effort for 30 min in 120 spontaneously breathing patients, before initiating HFNOT, CPAP, or NIV. Respiratory effort was then reduced progressively over 30-min intervals. Oxygenation, respiratory effort, and lung stress/strain were quantified. Lung-protective mechanical ventilation was also simulated in the same cohort.Results: HFNOT, CPAP, and NIV improved oxygenation compared with conventional therapy, but also initially increased total lung stress and strain. Improved oxygenation with CPAP reduced respiratory effort but lung stress/strain remained elevated for CPAP >5 cm H2O. With reduced respiratory effort, HFNOT maintained better oxygenation and reduced total lung stress, with no increase in total lung strain. Compared with 10 cm H2O PEEP, 4 cm H2O PEEP in NIV reduced total lung stress, but high total lung strain persisted even with less respiratory effort. Lung-protective mechanical ventilation improved oxygenation while minimising lung injury.Conclusions: The failure of noninvasive ventilatory support to reduce respiratory effort may exacerbate pulmonary injury in patients with early COVID-19 pneumonia. HFNOT reduces lung strain and achieves similar oxygenation to CPAP/NIV. Invasive mechanical ventilation may be less injurious than noninvasive support in patients with high respiratory effort. [ABSTRACT FROM AUTHOR]

Background: In non-traumatic respiratory failure, pre-hospital application of CPAP reduces the need for intubation. Primary blast lung injury (PBLI) accompanied by haemorrhagic shock is common after mass casualty incidents. We hypothesised that pre-hospital CPAP is also beneficial after PBLI accompanied by haemorrhagic shock.Methods: We performed a computer-based simulation of the cardiopulmonary response to PBLI followed by haemorrhage, calibrated from published controlled porcine experiments exploring blast injury and haemorrhagic shock. The effect of different CPAP levels was simulated in three in silico patients who had sustained mild, moderate, or severe PBLI (10%, 25%, 50% contusion of the total lung) plus haemorrhagic shock. The primary outcome was arterial partial pressure of oxygen (Pao2) at the end of each simulation.Results: In mild blast lung injury, 5 cm H2O ambient-air CPAP increased Pao2 from 10.6 to 12.6 kPa. Higher CPAP did not further improve Pao2. In moderate blast lung injury, 10 cm H2O CPAP produced a larger increase in Pao2 (from 8.5 to 11.1 kPa), but 15 cm H2O CPAP produced no further benefit. In severe blast lung injury, 5 cm H2O CPAP inceased Pao2 from 4.06 to 8.39 kPa. Further increasing CPAP to 10-15 cm H2O reduced Pao2 (7.99 and 7.90 kPa, respectively) as a result of haemodynamic impairment resulting from increased intrathoracic pressures.Conclusions: Our modelling study suggests that ambient air 5 cm H2O CPAP may benefit casualties suffering from blast lung injury, even with severe haemorrhagic shock. However, higher CPAP levels beyond 10 cm H2O after severe lung injury reduced oxygen delivery as a result of haemodynamic impairment. [ABSTRACT FROM AUTHOR]

Background: During induction of general anaesthesia a 'cannot intubate, cannot oxygenate' (CICO) situation can arise, leading to severe hypoxaemia. Evidence is scarce to guide ventilation strategies for small-bore emergency front of neck airways that ensure effective oxygenation without risking lung damage and cardiovascular depression.Methods: Fifty virtual subjects were configured using a high-fidelity computational model of the cardiovascular and pulmonary systems. Each subject breathed 100% oxygen for 3 min and then became apnoeic, with an obstructed upper airway. When arterial haemoglobin oxygen saturation reached 40%, front of neck airway access was simulated with various configurations. We examined the effect of several ventilation strategies on re-oxygenation, pulmonary pressures, cardiovascular function, and oxygen delivery.Results: Re-oxygenation was achieved in all ventilation strategies. Smaller airway configurations led to dynamic hyperinflation for a wide range of ventilation strategies. This effect was absent in airways with larger internal diameter (≥3 mm). Intrapulmonary pressures increased quickly to supra-physiological values with the smallest airways, resulting in pronounced cardio-circulatory depression (cardiac output <3 L min-1 and mean arterial pressure <60 mm Hg), impeding oxygen delivery (<600 ml min-1). Limiting tidal volume (≤200 ml) and ventilatory frequency (≤8 bpm) for smaller diameter cannulas reduced dynamic hyperinflation and gas trapping, preventing cardiovascular depression.Conclusions: Dynamic hyperinflation can be demonstrated for a wide range of front of neck airway cannulae when the upper airway is obstructed. When using small-bore cannulae in a CICO situation, ventilation strategies should be chosen that prevent gas trapping to prevent severe adverse events including cardio-circulatory depression. [ABSTRACT FROM AUTHOR]

Background: During induction of general anaesthesia, patients frequently experience apnoea, which can lead to dangerous hypoxaemia. An obstructed upper airway can impede attempts to provide ventilation. Although unrelieved apnoea is rare, it continues to cause deaths. Clinical investigation of management strategies for such scenarios is effectively impossible because of ethical and practical considerations.Methods: A population-representative cohort of 100 virtual (in silico) subjects was configured using a high-fidelity computational model of the pulmonary and cardiovascular systems. Each subject breathed 100% oxygen for 3 min and then became apnoeic, with an obstructed upper airway, during induction of general anaesthesia. Apnoea continued throughout the protocol. When arterial oxygen saturation (Sao2) reached 20%, 40%, or 60%, airway obstruction was relieved. We examined the effect of varying supraglottic oxygen fraction (Fo2) on the degree of passive re-oxygenation occurring without tidal ventilation.Results: Relief of airway obstruction during apnoea produced a single, passive inhalation (caused by intrathoracic hypobaric pressure) in all cases. The degree of re-oxygenation after airway opening was markedly influenced by the supraglottic Fo2, with a supraglottic Fo2 of 100% providing significant and sustained re-oxygenation (post-rescue Pao2 42.3 [4.4] kPa, when the airway rescue occurred after desaturation to Sao2 60%).Conclusions: Supraglottic oxygen supplementation before relieving upper airway obstruction improves the effectiveness of simulated airway rescue. Management strategies should be implemented to assure a substantially increased pharyngeal Fo2 during difficult airway management. [ABSTRACT FROM AUTHOR]