New Findings: What is the topic of this review? This review presents the fundamental concepts of respiratory physiology and pathophysiology, with particular reference to lung mechanics and the pulmonary phenotype associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and subsequent coronavirus disease 2019 (COVID‐19) pneumonia. What advances does it highlight? The review provides a critical summary of the main physiological aspects to be considered for safe and effective mechanical ventilation in patients with severe COVID‐19 in the intensive care unit. Severe respiratory failure from coronavirus disease 2019 (COVID‐19) pneumonia not responding to non‐invasive respiratory support requires mechanical ventilation. Although ventilation can be a life‐saving therapy, it can cause further lung injury if airway pressure and flow and their timing are not tailored to the respiratory system mechanics of the individual patient. The pathophysiology of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection can lead to a pattern of lung injury in patients with severe COVID‐19 pneumonia typically associated with two distinct phenotypes, along a temporal and pathophysiological continuum, characterized by different levels of elastance, ventilation‐to‐perfusion ratio, right‐to‐left shunt, lung weight and recruitability. Understanding the underlying pathophysiology, duration of symptoms, radiological characteristics and lung mechanics at the individual patient level is crucial for the appropriate choice of mechanical ventilation settings to optimize gas exchange and prevent further lung injury. By critical analysis of the literature, we propose fundamental physiological and mechanical criteria for the selection of ventilation settings for COVID‐19 patients in intensive care units. In particular, the choice of tidal volume should be based on obtaining a driving pressure < 14 cmH₂O, ensuring the avoidance of hypoventilation in patients with preserved compliance and of excessive strain in patients with smaller lung volumes and lower lung compliance. The level of positive end‐expiratory pressure (PEEP) should be informed by the measurement of the potential for lung recruitability, where patients with greater recruitability potential may benefit from higher PEEP levels. Prone positioning is often beneficial and should be considered early. The rationale for the proposed mechanical ventilation settings criteria is presented and discussed.

Inhibitory mechanisms are essential in suppressing the development of allodynia and hyperalgesia in the normal animal and there is evidence that loss of inhibition can lead to the development of neuropathic pain. We used Fos expression to map the distribution of tonically inhibited cells in the healthy rat lumbar spinal cord. In a control group, Fos-like immunoreactive (Fos-LI) cells were rare, averaging 7.5+/-2.2 cells (mean+/-SEM; N=13 sections) per 20 microm thick section of dorsal horn. This rose to 103+/-11 (mean+/-SEM; N=20) in picrotoxin-treated rats and to 88+/-11 (mean+/-SEM; N=18) in strychnine-treated rats. These changes were significant (ANOVA; P<0.001). There were marked regional variations in the distribution of Fos-LI cells between picrotoxin- and strychnine-treated animals. Picrotoxin induced a significant increase in the number of Fos-LI cells throughout the dorsal horn (lamina I-VI) while strychnine significantly elevated Fos-like immunoreactivity only in deep laminae (III-VI). For both picrotoxin and strychnine, the increase in Fos-like immunoreactivity peaked in lamina V (at 3579+/-319 and 3649+/-375% of control, respectively; mean+/-SEM) but for picrotoxin an additional peak was observed in the outer part of lamina II (1959+/-196%). Intrathecal administration of both GABAA and glycine receptor antagonists has been shown elsewhere to induce tactile allodynia. The present data suggest that this allodynia could arise due to blockade of tonic GABAA and glycine-receptor mediated inhibition in the deep dorsal horn. GABAA antagonists also induce hypersensitivity to noxious inputs. The blockade of tonic inhibition in the superficial dorsal horn shown here may underlie this hyperalgesia.

Arterial oxygen partial pressure can increase during inspiration and decrease during expiration in the presence of a variable shunt fraction, such as with cyclical atelectasis, but it is generally presumed to remain constant within a respiratory cycle in the healthy lung. We measured arterial oxygen partial pressure continuously with a fast intra-vascular sensor in the carotid artery of anaesthetized, mechanically ventilated pigs, without lung injury. Here we demonstrate that arterial oxygen partial pressure shows respiratory oscillations in the uninjured pig lung, in the absence of cyclical atelectasis (as determined with dynamic computed tomography), with oscillation amplitudes that exceeded 50 mmHg, depending on the conditions of mechanical ventilation. These arterial oxygen partial pressure respiratory oscillations can be modelled from a single alveolar compartment and a constant oxygen uptake, without the requirement for an increased shunt fraction during expiration. Our results are likely to contribute to the interpretation of arterial oxygen respiratory oscillations observed during mechanical ventilation in the acute respiratory distress syndrome.

Background: Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (V_T) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs.Methods: One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injuredgroup). Four ventilated piglets served as thecontrolgroup. A randomized sequence of any possible combination of threeV_T(7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH₂O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group:interventionorcontrol), and two within-subjects factors (PEEP andV_T) was used, with a three-way mixed analysis of variance (ANOVA).Results: Two-way interactions between PEEP and group, andV_Tand group, were observed for the dependent ROI (p= 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and V_Tin the injured group than in the control group. A two-way interaction between PEEP andV_Twas observed for perfusion distribution in each ROI: nondependent (p= 0.030), middle (p= 0.006), and dependent (p= 0.001); no interaction was observed between injured and control groups.Conclusions: Large PEEP andV_Tlevels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.

Summary: The perceived risk of transmission of aerosolised viral particles from patients to airway practitioners during the COVID‐19 pandemic led to the widespread use of aerosol precautions, including personal protective equipment and modifications to anaesthetic technique. The risk of these aerosol precautions on peri‐operative airway complications has not been assessed outside of simulation studies. This prospective, national, multicentre cohort study aimed to quantify this risk. Adult patients undergoing general anaesthesia for elective or emergency procedures over a 96‐hour period were included. Data collected included use of aerosol precautions by the airway practitioner, airway complications and potential confounding variables. Mixed‐effects logistic regression was used to assess the risk of individual aerosol precautions on overall and specific airway complications. Data from 5905 patients from 70 hospital sites were included. The rate of airway complications was 10.0% (95%CI 9.2–10.8%). Use of filtering facepiece class 2 or class 3 respirators was associated with an increased risk of airway complications (odds ratio 1.38, 95%CI 1.04–1.83), predominantly due to an association with difficult facemask ventilation (odds ratio 1.68, 95%CI 1.09–2.61) and desaturation on pulse oximetry (odds ratio 2.39, 95%CI 1.26–4.54). Use of goggles, powered air‐purifying respirators, long‐sleeved gowns, double gloves and videolaryngoscopy were not associated with any alteration in the risk of airway complications. Overall, the use of filtering facepiece class 2 or class 3 respirators was associated with an increased risk of airway complications, but most aerosol precautions used during the COVID‐19 pandemic were not.