Impact of spinal or epidural anaesthesia on perioperative outcomes in adult noncardiac surgery: a narrative review of recent evidence.

Spinal and epidural anaesthesia and analgesia are important anaesthetic techniques, familiar to all anaesthetists and applied to patients undergoing a range of surgical procedures. Although the immediate effects of a well-conducted neuraxial technique on nociceptive and sympathetic pathways are readily observable in clinical practice, the impact of such techniques on patient-centred perioperative outcomes remains an area of uncertainty and active research. The aim of this review is to present a narrative synthesis of contemporary clinical science on this topic from the most recent 5-year period and summarise the foundational scholarship upon which this research was based. We searched electronic databases for primary research, secondary research, opinion pieces, and guidelines reporting the relationship between neuraxial procedures and standardised perioperative outcomes over the period 2018-2023. Returned citation lists were examined seeking additional studies to contextualise our narrative synthesis of results. Articles were retrieved encompassing the following outcome domains: patient comfort, renal, sepsis and infection, postoperative cancer, cardiovascular, and pulmonary and mortality outcomes. Convincing evidence of the beneficial effect of epidural analgesia on patient comfort after major open thoracoabdominal surgery outcomes was identified. Recent evidence of benefit in the prevention of pulmonary complications and mortality was identified. Despite mechanistic plausibility and supportive observational evidence, there is less certain experimental evidence to support a role for neuraxial techniques impacting on other outcome domains. Evidence of positive impact of neuraxial techniques is best established for the domains of patient comfort, pulmonary complications, and mortality, particularly in the setting of major open thoracoabdominal surgery. Recent evidence does not strongly support a significant impact of neuraxial techniques on cancer, renal, infection, or cardiovascular outcomes after noncardiac surgery in most patient groups.

The Making of Corporate Legal Concession Theory.

Professor Watson's The Making of the Modern Company traces the development of the modern corporate form back to the East India Company, disproving a common notion that company law originated solely with small, private companies. This review article argues three key implications of this excellent book. First, Watson focuses on the duality of the modern company-with state-provided and private features. This cuts through, and goes a long way to resolving, the ongoing historic debate as to the nature of the company. Second, the primary unit of study chosen-the modern company-reminds corporate lawyers of our role in studying this duality in a very crowded field. Third, despite eschewing 'concession theories' of company law (which hold that the company is merely a concession from the state), Watson demonstrates a role for the state in the modern company that is often overlooked.

Developing an Artificial Intelligence-Based Representation of a Virtual Patient Model for Real-Time Diagnosis of Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) is a condition that endangers the lives of many Intensive Care Unit patients through gradual reduction of lung function. Due to its heterogeneity, this condition has been difficult to diagnose and treat, although it has been the subject of continuous research, leading to the development of several tools for modeling disease progression on the one hand, and guidelines for diagnosis on the other, mainly the "Berlin Definition". This paper describes the development of a deep learning-based surrogate model of one such tool for modeling ARDS onset in a virtual patient: the Nottingham Physiology Simulator. The model-development process takes advantage of current machine learning and data-analysis techniques, as well as efficient hyperparameter-tuning methods, within a high-performance computing-enabled data science platform. The lightweight models developed through this process present comparable accuracy to the original simulator (per-parameter R2 > 0.90). The experimental process described herein serves as a proof of concept for the rapid development and dissemination of specialised diagnosis support systems based on pre-existing generalised mechanistic models, making use of supercomputing infrastructure for the development and testing processes and supported by open-source software for streamlined implementation in clinical routines.

Postoperative ulnar neuropathy: a systematic review of evidence with narrative synthesis.

BACKGROUND: Postoperative ulnar neuropathy (PUN) is an injury manifesting in the sensory or motor distribution of the ulnar nerve after anaesthesia or surgery. The condition frequently features in cases of alleged clinical negligence by anaesthetists. We performed a systematic review and applied narrative synthesis with the aim of summarising current understanding of the condition and deriving implications for practice and research. METHODS: Electronic databases were searched up to October 2022 for primary research, secondary research, or opinion pieces defining PUN and describing its incidence, predisposing factors, mechanism of injury, clinical presentation, diagnosis, management, and prevention. RESULTS: We included 83 articles in the thematic analysis. PUN occurs after approximately 1 in 14 733 anaesthetics. Men aged 50-75 yr with pre-existing ulnar neuropathy are at highest risk. Preventative measures, based on consensus and expert opinion, are summarised, and an algorithm of suspected PUN management is proposed, based upon the identified literature. CONCLUSIONS: Postoperative ulnar neuropathy is rare and the incidence is probably decreasing over time with general improvements in perioperative care. Recommendations to reduce the risk of postoperative ulnar neuropathy are based on low-quality evidence but include anatomically neutral arm positioning and padding intraoperatively. In selected high-risk patients, further documentation of repositioning, intermittent checks, and neurological examination in the recovery room can be helpful.

Evaluating current guidelines for cardiopulmonary resuscitation using an integrated computational model of the cardiopulmonary system.

OBJECTIVE: We aimed to use a high-fidelity computational model that captures key interactions between the cardiovascular and pulmonary systems to investigate whether current CPR protocols could potentially be improved. METHODS: We developed and validated the computational model against available human data. We used a global optimisation algorithm to find CPR protocol parameters that optimise the outputs associated with return of spontaneous circulation in a cohort of 10 virtual subjects. RESULTS: Compared with current protocols, myocardial tissue oxygen volume was more than 5 times higher, and cerebral tissue oxygen volume was nearly doubled, during optimised CPR. While the optimal maximal sternal displacement (5.5 cm) and compression ratio (51%) found using our model agreed with the current American Heart Association guidelines, the optimal chest compression rate was lower (67 compressions min-1). Similarly, the optimal ventilation strategy was more conservative than current guidelines, with an optimal minute ventilation of 1500 ml min-1 and inspired fraction of oxygen of 80%. The end compression force was the parameter with the largest impact on CO, followed by PEEP, the compression ratio and the CC rate. CONCLUSIONS: Our results indicate that current CPR protocols could potentially be improved. Excessive ventilation could be detrimental to organ oxygenation during CPR, due to the negative haemodynamic effect of increased pulmonary vascular resistance. Particular attention should be given to the chest compression force to achieve satisfactory CO. Future clinical trials aimed at developing improved CPR protocols should explicitly consider interactions between chest compression and ventilation parameters.

Clinical hypnosis: implications in anaesthesia and perioperative care.

A randomised trial published in the British Journal of Anaesthesia describes hypnosis compared with general anaesthesia in 60 children undergoing superficial surgery. We describe a definition of clinical hypnosis; the goals and conduct of hypnotic communication; and its potential as both an adjunct and, in suitable cases, alternative to traditional pharmacological anaesthesia.

Why Reduced Inspiratory Pressure Could Determine Success of Non-Invasive Ventilation in Acute Hypoxic Respiratory Failure.

The magnitude of inspiratory effort relief within the first 2 hours of non-invasive ventilation for hypoxic respiratory failure was shown in a recent exploratory clinical study to be an early and accurate predictor of outcome at 24 hours. We simulated the application of non-invasive ventilation to three patients whose physiological and clinical characteristics match the data in that study. Reductions in inspiratory effort corresponding to reductions of esophageal pressure swing greater than 10 cmH2O more than halved the values of total lung stress, driving pressure, power and transpulmonary pressure swing. In the absence of significant reductions in inspiratory pressure, multiple indicators of lung injury increased after application of non-invasive ventilation. Clinical Relevance- We show using computer simulation that reduced inspiratory pressure after application of noninvasive ventilation translates directly into large reductions in multiple well-established indicators of lung injury, providing a potential physiological explanation for recent clinical findings.

A computational cardiopulmonary physiology simulator accurately predicts individual patient responses to changes in mechanical ventilator settings.

We present new results validating the capability of a high-fidelity computational simulator to accurately predict the responses of individual patients with acute respiratory distress syndrome to changes in mechanical ventilator settings. 26 pairs of data-points comprising arterial blood gasses collected before and after changes in inspiratory pressure, PEEP, FiO2, and I:E ratio from six mechanically ventilated patients were used for this study. Parallelized global optimization algorithms running on a high-performance computing cluster were used to match the simulator to each initial data point. Mean absolute percentage errors between the simulator predicted values of PaO2 and PaCO2 and the patient data after changing ventilator parameters were 10.3% and 12.6%, respectively. Decreasing the complexity of the simulator by reducing the number of independent alveolar compartments reduced the accuracy of its predictions. Clinical Relevance- These results provide further evidence that our computational simulator can accurately reproduce patient responses to mechanical ventilation, highlighting its usefulness as a clinical research tool.

Comparison of apnoeic oxygen techniques in term pregnant subjects: a computational modelling study.

BACKGROUND: Hypoxaemia during general anaesthesia can cause harm. Apnoeic oxygenation extends safe apnoea time, reducing risk during airway management. We hypothesised that low-flow nasal oxygenation (LFNO) would extend safe apnoea time similarly to high-flow nasal oxygenation (HFNO), whilst allowing face-mask preoxygenation and rescue. METHODS: A high-fidelity, computational, physiological model was used to examine the progression of hypoxaemia during apnoea in virtual models of pregnant women in and out of labour, with BMI of 24-50 kg m-2. Subjects were preoxygenated with oxygen 100% to reach end-tidal oxygen fraction (FE'O2) of 60%, 70%, 80%, or 90%. When apnoea started, HFNO or LFNO was commenced. To simulate varying degrees of effectiveness of LFNO, periglottic oxygen fraction (FgO2) of 21%, 60%, or 100% was configured. HFNO provided FgO2 100% and oscillating positive pharyngeal pressure. RESULTS: Application of LFNO (FgO2 100%) after optimal preoxygenation (FE'O2 90%) resulted in similar or longer safe apnoea times than HFNO FE'O2 80% in all subjects in labour. For BMI of 24, the time to reach SaO2 90% with LFNO was 25.4 min (FE'O2 90%/FgO2 100%) vs 25.4 min with HFNO (FE'O2 80%). For BMI of 50, the time was 9.9 min with LFNO (FE'O2 90%/FgO2 100%) vs 4.3 min with HFNO (FE'O2 80%). A similar finding was seen in subjects with BMI ≥40 kg m-2 not in labour. CONCLUSIONS: There is likely to be clinical benefit to using LFNO, given that LFNO and HFNO extend safe apnoea time similarly, particularly when BMI ≥40 kg m-2. Additional benefits to LFNO include the facilitation of rescue face-mask ventilation and ability to monitor FE'O2 during preoxygenation.

Modeling Mechanical Ventilation In Silico-Potential and Pitfalls.

Computer simulation offers a fresh approach to traditional medical research that is particularly well suited to investigating issues related to mechanical ventilation. Patients receiving mechanical ventilation are routinely monitored in great detail, providing extensive high-quality data-streams for model design and configuration. Models based on such data can incorporate very complex system dynamics that can be validated against patient responses for use as investigational surrogates. Crucially, simulation offers the potential to "look inside" the patient, allowing unimpeded access to all variables of interest. In contrast to trials on both animal models and human patients, in silico models are completely configurable and reproducible; for example, different ventilator settings can be applied to an identical virtual patient, or the same settings applied to different patients, to understand their mode of action and quantitatively compare their effectiveness. Here, we review progress on the mathematical modeling and computer simulation of human anatomy, physiology, and pathophysiology in the context of mechanical ventilation, with an emphasis on the clinical applications of this approach in various disease states. We present new results highlighting the link between model complexity and predictive capability, using data on the responses of individual patients with acute respiratory distress syndrome to changes in multiple ventilator settings. The current limitations and potential of in silico modeling are discussed from a clinical perspective, and future challenges and research directions highlighted.

Validation of at-the-bedside formulae for estimating ventilator driving pressure during airway pressure release ventilation using computer simulation.

BACKGROUND: Airway pressure release ventilation (APRV) is widely available on mechanical ventilators and has been proposed as an early intervention to prevent lung injury or as a rescue therapy in the management of refractory hypoxemia. Driving pressure ([Formula: see text]) has been identified in numerous studies as a key indicator of ventilator-induced-lung-injury that needs to be carefully controlled. [Formula: see text] delivered by the ventilator in APRV is not directly measurable in dynamic conditions, and there is no "gold standard" method for its estimation. METHODS: We used a computational simulator matched to data from 90 patients with acute respiratory distress syndrome (ARDS) to evaluate the accuracy of three "at-the-bedside" methods for estimating ventilator [Formula: see text] during APRV. RESULTS: Levels of [Formula: see text] delivered by the ventilator in APRV were generally within safe limits, but in some cases exceeded levels specified by protective ventilation strategies. A formula based on estimating the intrinsic positive end expiratory pressure present at the end of the APRV release provided the most accurate estimates of [Formula: see text]. A second formula based on assuming that expiratory flow, volume and pressure decay mono-exponentially, and a third method that requires temporarily switching to volume-controlled ventilation, also provided accurate estimates of true [Formula: see text]. CONCLUSIONS: Levels of [Formula: see text] delivered by the ventilator during APRV can potentially exceed levels specified by standard protective ventilation strategies, highlighting the need for careful monitoring. Our results show that [Formula: see text] delivered by the ventilator during APRV can be accurately estimated at the bedside using simple formulae that are based on readily available measurements.

Optimising respiratory support for early COVID-19 pneumonia: a computational modelling study.

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.

Intra-tracheal multiplexed sensing of contact pressure and perfusion.

Incorrect endotracheal tube (ETT) cuff inflation pressure causes significant problems for intubated patients. The technical development and first in vivo use of a smart ETT for measurements at the cuff-trachea interface during mechanical ventilation are described. The intra-tracheal multiplexed sensing (iTraXS) ETT contains integrated optical fibre sensors to measure contact pressure and blood perfusion. The device is tested during mechanical ventilation in a porcine model (N=6). For contact pressure, signals were obtained in all 30 measurements. For perfusion, data could be obtained in all 33 measurements. In the 3 cases where the cuff was inflated to an artificially high-level, blood occlusion is observed.

Pre-hospital continuous positive airway pressure after blast lung injury and hypovolaemic shock: a modelling study.

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.

Patient-maintained versus anaesthetist-controlled propofol sedation during elective primary lower-limb arthroplasty performed under spinal anaesthesia: a randomised controlled trial.

BACKGROUND: Patient-maintained propofol TCI sedation (PMPS) allows patients to titrate their own target-controlled infusion (TCI) delivery of propofol sedation using a handheld button. The aim of this RCT was to compare PMPS with anaesthetist-controlled propofol TCI sedation (ACPS) in patients undergoing elective primary lower-limb arthroplasty surgery under spinal anaesthesia. METHODS: In this single-centre open-label investigator-led study, adult patients were randomly assigned to either PMPS or ACPS during their surgery. Both sedation regimes used Schnider effect-site TCI modelling. The primary outcome measure was infusion rate adjusted for weight (expressed as mg kg-1 h-1). Secondary outcomes measures included depth of sedation, occurrence of sedation-related adverse events and time to medical readiness for discharge from the postanaesthsia care unit (PACU). RESULTS: Eighty patients (48 female) were randomised. Subjects using PMPS used 39.3% less propofol during the sedation period compared with subjects in group ACPS (1.56 [0.57] vs 2.57 [1.33] mg kg-1 h-1; P<0.001), experienced fewer discrete episodes of deep sedation (0 vs 6; P=0.0256), fewer airway/breathing adverse events (odds ratio [95% confidence interval]: 2.94 [1.31-6.64]; P=0.009) and were ready for discharge from PACU more quickly (8.94 [5.5] vs 13.51 [7.2] min; P=0.0027). CONCLUSIONS: Patient-maintained propofol sedation during lower-limb arthroplasty under spinal anaesthesia results in reduced drug exposure and fewer episodes of sedation-related adverse events compared with anaesthetist-controlled propofol TCI sedation. To facilitate further investigation of this procedural sedation technique, PMPS-capable TCI infusion devices should be submitted for regulatory approval for clinical use. CLINICAL TRIAL REGISTRATION: ISRCTN29129799.

High risk of patient self-inflicted lung injury in COVID-19 with frequently encountered spontaneous breathing patterns: a computational modelling study.

BACKGROUND: There is on-going controversy regarding the potential for increased respiratory effort to generate patient self-inflicted lung injury (P-SILI) in spontaneously breathing patients with COVID-19 acute hypoxaemic respiratory failure. However, direct clinical evidence linking increased inspiratory effort to lung injury is scarce. We adapted a computational simulator of cardiopulmonary pathophysiology to quantify the mechanical forces that could lead to P-SILI at different levels of respiratory effort. In accordance with recent data, the simulator parameters were manually adjusted to generate a population of 10 patients that recapitulate clinical features exhibited by certain COVID-19 patients, i.e., severe hypoxaemia combined with relatively well-preserved lung mechanics, being treated with supplemental oxygen. RESULTS: Simulations were conducted at tidal volumes (VT) and respiratory rates (RR) of 7 ml/kg and 14 breaths/min (representing normal respiratory effort) and at VT/RR of 7/20, 7/30, 10/14, 10/20 and 10/30 ml/kg / breaths/min. While oxygenation improved with higher respiratory efforts, significant increases in multiple indicators of the potential for lung injury were observed at all higher VT/RR combinations tested. Pleural pressure swing increased from 12.0 ± 0.3 cmH2O at baseline to 33.8 ± 0.4 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 46.2 ± 0.5 cmH2O at 10 ml/kg/30 breaths/min. Transpulmonary pressure swing increased from 4.7 ± 0.1 cmH2O at baseline to 17.9 ± 0.3 cmH2O at VT/RR of 7 ml/kg/30 breaths/min and to 24.2 ± 0.3 cmH2O at 10 ml/kg/30 breaths/min. Total lung strain increased from 0.29 ± 0.006 at baseline to 0.65 ± 0.016 at 10 ml/kg/30 breaths/min. Mechanical power increased from 1.6 ± 0.1 J/min at baseline to 12.9 ± 0.2 J/min at VT/RR of 7 ml/kg/30 breaths/min, and to 24.9 ± 0.3 J/min at 10 ml/kg/30 breaths/min. Driving pressure increased from 7.7 ± 0.2 cmH2O at baseline to 19.6 ± 0.2 cmH2O at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9 ± 0.3 cmH2O at 10 ml/kg/30 breaths/min. CONCLUSIONS: Our results suggest that the forces generated by increased inspiratory effort commonly seen in COVID-19 acute hypoxaemic respiratory failure are comparable with those that have been associated with ventilator-induced lung injury during mechanical ventilation. Respiratory efforts in these patients should be carefully monitored and controlled to minimise the risk of lung injury.

Ventilation strategies for front of neck airway rescue: an in silico study.

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.

Effect of variable pre-oxygenation endpoints on safe apnoea time using high flow nasal oxygen for women in labour: a modelling investigation.

BACKGROUND: Studies of pulmonary denitrogenation (pre-oxygenation) in obstetric populations have shown high flow nasal oxygen therapy (HFNO) is inferior to facemask techniques. HFNO achieves median end-tidal oxygen fraction (FE'O2) of 0.87 after 3 min. As HFNO prolongs safe apnoea times through apnoeic oxygenation, we postulated that HFNO would still extend safe apnoeic times despite the lower FE'O2 after pre-oxygenation. METHODS: The Interdisciplinary Collaboration in Systems Medicine simulation suite, a highly integrated, high-fidelity model of the human respiratory and cardiovascular systems, was used to study the effect of varying FE'O2 (60%, 70%, 80%, and 90%) on the duration of safe apnoea times using HFNO and facemask techniques (with the airway open and obstructed). The study population consisted of validated models of pregnant women in active labour and not in labour with BMI of 24, 35, 40, 45, and 50 kg m-2. RESULTS: HFNO provided longer safe apnoeic times in all models, with all FE'O2 values. Labour and increased BMI reduced this effect, in particular a BMI of 50 kg m-2 reduced the improvement in apnoea time to 1.8-8.5 min (depending on the FE'O2), compared with an improvement of more than 60 min in the subject with BMI 24 kg m-2. CONCLUSIONS: Despite generating lower FE'O2, HFNO provides longer safe apnoea times in pregnant subjects in labour. Care should be taken when used in patients with BMI ≥50 kg m-2 as the extension of the safe apnoea time is limited.