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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.

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.

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.

BackgroundThere 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.ResultsSimulations 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 at VT/RR of 7 ml/kg/30 breaths/min, and to 26.9±0.3 cmH2O at 10 ml/kg/30 breaths/min.ConclusionsOur 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.

BackgroundThe novel coronavirus SARS-CoV-2 and associated multisystem disease COVID-19 originated in Wuhan, China in December 2019. The resultant pandemic has resulted in an unprecedented strain on healthcare services around the world, including the greatest challenge seen by critical care medicine in modern times. This narrative illustrates the response of Nottingham University Hospitals NHS Trust critical care department to the crisis, including resource allocation and clinical management strategies and illustrates patient outcome for those admitted to critical care during the first pandemic wave.MethodsPatients admitted to critical care whom tested positive for SARS-CoV-2 between March-May 2020 were identified for retrospective case review as part of service evaluation. Clinical, laboratory and radiological data was collected. This included patient level data on ventilation and fluid balance.ResultsDuring the three period March-May 2020, retrospective case review showed 109 patients admitted to critical care with COVID-19. 88 (80.7%) of the 109 patients received mechanical ventilation, 21 (19.3%) patients received renal replacement therapy. Critical care mortality was 26 (23.9%) patients and hospital mortality was 27 (24.8%) of the 109 patients.ConclusionThis mortality rate was an unexpected finding based on early literature and help to provide a baseline for comparison hereafter. Commentary is provided for several aspects of care that may account for the low mortality rate and warrant further investigation in the future.

Objectives To explore and describe current UK physiotherapy practice relating to airway clearance techniques and mucoactive agents in critically ill adult patients with acute respiratory failure in the intensive care unit. Design A descriptive, qualitative study using focus group interviews. Focus groups were audio-recorded, independently transcribed, and data analysed thematically. Participants Senior, experienced physiotherapists, clinically active in critical care. Results Fifteen physiotherapists participated in four interview sessions. Five themes emerged describing airway clearance techniques: 'Repertoire of airway clearance techniques', 'Staffing and skillset', 'Commencing respiratory physiotherapy', 'Technique selection', and 'Determining effectiveness' were themes related to airway clearance techniques. Five themes were also identified in relation to mucoactive agents: 'Use in clinical practice', 'Decision to commence', 'Selection of agent', 'Stopping mucoactive agents', and 'Determining effectiveness'. A summary of key features of standard practice was developed. Conclusions Standard UK physiotherapy practice of airway clearance techniques is variable, but patient-centred and targeted to individual need, with adjunctive use of mucoactive agents to enhance and optimise patient management if required. Based on this study, key features of airway clearance techniques have been summarised to help capture standard care, which could be used in future trials involving ACT as part of usual care.

Supplemental Digital Content is available in the text., Objectives: Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the “baby lung” (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management. Design: We adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings. Setting: Interdisciplinary Collaboration in Systems Medicine Research Network. Subjects: The simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. Interventions: None. Measurements and Main Results: An acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model. Conclusions: Our model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.

ObjectivesPatients with COVID-19 Acute Respiratory Distress Syndrome (CARDS) appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (Type 1) and a more conventional ARDS phenotype displaying the typical characteristics of the ‘baby lung’ (Type 2). We aimed to test plausible hypotheses regarding the pathophysiological mechanisms underlying CARDS, and to evaluate the resulting implications for ventilatory management.DesignWe adapted a high-fidelity computational simulator, previously validated in several studies of ARDS, to (a) develop quantitative insights into the key pathophysiologic differences between CARDS and conventional ARDS, and (b) assess the impact of different PEEP, FiO2 and tidal volume settings.SettingInterdisciplinary Collaboration in Systems Medicine Research Network.SubjectsThe simulator was calibrated to represent CARDS patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation.Measurements and Main ResultsAn ARDS model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on Type 1 CARDS patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis, and heightened vascular resistance due to the emergence of microthrombi, produced levels of V/Q mismatch and hypoxemia consistent with data from Type 1 CARDS patients, while preserving close to normal lung compliance and gas volumes. Atypical responses to PEEP increments between 5 and 15 cmH2O were observed for this Type 1 CARDS model across a range of measures: increasing PEEP resulted in reduced lung compliance and no improvement in oxygenation, while Mechanical Power, Driving Pressure and Plateau Pressure all increased. FiO2 settings based on ARDSnet protocols at different PEEP levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 ml/kg produced similar increases in multiple indicators of ventilator induced lung injury in the Type 1 CARDS model to those seen in a conventional ARDS model.ConclusionsOur model suggests that use of standard PEEP/ FiO2 tables, higher PEEP strategies, and higher tidal volumes, may all be potentially deleterious in Type 1 CARDS patients, and that a highly personalized approach to treatment is advisable.

Background Mechanical ventilation for acute respiratory failure is one of the most common indications for admission to intensive care units (ICUs). Airway mucus clearance is impaired in these patients medication, impaired mucociliary motility, increased mucus production etc. and mucoactive agents have the potential to improve outcomes. However, studies to date have provided inconclusive results. Despite this uncertainty, mucoactives are used in adult ICUs, although the extent of use and perceptions about place in therapy are not known. Aims and Objectives We aim to describe the use of mucoactive agents in mechanically ventilated patients in UK adult critical care units. Specifically, our objectives are to describe clinicians perceptions about the use of mucoactive agents, understand the indications and anticipated benefits, and describe the prevalence and type of mucoactive agents in use. Methods We conducted three surveys. Firstly, a practitioner-level survey aimed at nurses, physiotherapists and doctors to elucidate individual practitioners perceptions about the use of mucoactive agents. Secondly, a critical care unit-level survey aimed at pharmacists to understand how these perceptions translate into practice. Thirdly, a point prevalence survey to describe the extent of prescribing and range of products in use. The practitioner-level survey was disseminated through the UK Intensive Care Society for completion by a multi-professional membership. The unit-level and point prevalence surveys were disseminated cthrough the UK Clinical Pharmacy Association for completion by pharmacists. Results The individual practitioners survey ranked ‘thick secretions’ as the main reason for commencing mucoactive agents determined using clinical assessment. The highest ranked perceived benefit for patient centred outcomes was the duration of ventilation. Of these respondents, 79% stated that further research was important and 87% expressed support for a clinical trial. The unit-level survey found that mucoactive agents were used in 83% of units. The most highly ranked indication was again ‘thick secretions’ and the most highly ranked expected patient centred clinical benefit being improved gas exchange and reduced ventilation time. Only five critical care units provided guidelines to direct the use of mucoactive agents (4%). In the point prevalence survey, 411/993 (41%) of mechanically ventilated patients received at least one mucoactive agent. The most commonly administered mucoactives were inhaled sodium chloride 0.9% (235/993, 24%), systemic carbocisteine (161/993, 16%) and inhaled hypertonic sodium cloride (127/993, 13%). Conclusions Mucoactive agents are used extensively in mechanically ventilated adult patients in UK ICUs to manage ‘thick secretions’, with a key aim to reduce the duration of ventilation. There is widespread support for clinical trials to determine the optimal use of mucoactive agent therapy in this patient population.

Summary 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 FiO2 1.0, before inducing apnoea. We found that increasing FiO2 at the open glottis increased the time to desaturation, extending the time taken for SaO2 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 FiO2 0.4–0.6, which could be delivered by standard nasal cannulae. The greatest increases in time to desaturation were seen at FiO2 1.0, which could be delivered by high-flow nasal cannulae under ideal conditions.

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.

Background Sepsis represents a significant public health burden, costing the NHS £2.5 billion annually, with 35% mortality in 2006. The aim of this exploratory study was to investigate risk factors predictive of 30-day mortality amongst patients with sepsis in Nottingham. Methods Data were collected prospectively from adult patients with sepsis in Nottingham University Hospitals NHS Trust as part of an on-going quality improvement project between November 2011 and March 2014. Patients admitted to critical care with the diagnosis of sepsis were included in the study. In all, 97 separate variables were investigated for their association with 30-day mortality. Variables included patient demographics, symptoms of systemic inflammatory response syndrome, organ dysfunction or tissue hypoperfusion, locations of early care, source of sepsis and time to interventions. Results A total of 455 patients were included in the study. Increased age (adjOR = 1.05 95%CI = 1.03–1.07 p Conclusion Several important predictors of 30-day mortality were found by this research. Retrospective analysis of our sepsis data has revealed mortality predictors that appear to be more patient-related than intervention-specific. With this information, care can be improved for those identified most at risk of death.

Background 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 RMs on the cardiovascular system remain poorly understood. Methods A 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. Results The 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. Conclusions Our 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. Electronic supplementary material The online version of this article (doi:10.1186/s12890-017-0369-7) contains supplementary material, which is available to authorized users.

Gaseous mixing in the anatomical deadspace with stimulation of respiratory ventilation through cardiogenic oscillations is an important physiological mechanism at the onset of apnea, which has been credited with various beneficial effects, e.g. reduction of hypercapnia during the use of low flow ventilation techniques. In this paper, a novel method is proposed to investigate the effect of these mechanisms in silico. An existing computational model of cardio-pulmonary physiology is extended to include the apneic state, gas mixing within the anatomical deadspace, insufflation into the trachea and cardiogenic oscillations. The new model is validated against data published in an experimental animal (dog) study that reported an increase in arterial partial pressure of carbon dioxide (PaCO 2 ) during apnea. Computational simulations confirm that the model outputs accurately reproduce the available experimental data. This new model can be used to investigate the physiological mechanisms underlying clearance of carbon dioxide during apnea, and hence to develop more effective ventilation strategies for apneic patients.

This paper presents the methodology used in patient-specific calibration of a novel highly integrated model of the cardiovascular and pulmonary pathophysiology associated with Acute Respiratory Distress Syndrome (ARDS). We focus on data from previously published clinical trials on the static and dynamic cardio-pulmonary responses of three ARDS patients to changes in ventilator settings. From this data, the parameters of the integrated model were identified using an optimization-based methodology in multiple stages. Computational simulations confirm that the resulting model outputs accurately reproduce the available clinical data. Our results open up the possibility of creating in silico a biobank of virtual ARDS patients that could be used to evaluate current, and investigate novel, therapeutic strategies.

The early recognition and goal-directed management of severely septic patients has been shown to reduce mortality. This study aimed to determine compliance with the ‘Surviving Sepsis' guidelines and to analyse the systems involved in delivering care in a UK teaching hospital. Patients from any hospital department with clinically significant positive blood cultures (n=229) were identified. Adults who met criteria for severe sepsis and who were deemed suitable for active management were included (n=46). None of the patients received all bundle elements within the advised time limits. Only 52% had received broad-spectrum antibiotics within three hours of presentation and only 57% had adequate fluid resuscitation within six hours. The median time from presentation to doctor involvement was 1.1 hours, with a delay of 3.9 hours to see a senior clinician. The median time from presentation to admission to the high dependency unit (HDU) or intensive care unit (ICU) was 12.9 hours. This study has shown that the early recognition and resuscitation of septic patients is unreliable and the capacity to provide early antimicrobial and goal-directed therapy for septic patients is limited in a UK teaching hospital.

We describe the development of an integrated cardiovascular and pulmonary model for use in the investigation of novel mechanical ventilation strategies in the intensive care unit. The cardiac model includes the cardiac chambers, the pulmonary circulation and the systemic circulation. The modeling of complex mechanisms for vascular segments, time varying elastance functions of cardiovascular components and the effect of vascular resistances, in health and disease under the influence of mechanical ventilation is investigated. The resulting biomedical simulator can aid in understanding the underlying pathophysiology of critically-ill patients and facilitate the development of more effective therapeutic strategies for evaluation in clinical trials.

Summary 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 FiO2 1.0, before inducing apnoea. We found that increasing FiO2 at the open glottis increased the time to desaturation, extending the time taken for SaO2 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 FiO2 0.4–0.6, which could be delivered by standard nasal cannulae. The greatest increases in time to desaturation were seen at FiO2 1.0, which could be delivered by high-flow nasal cannulae under ideal conditions.

Background Computer simulation models could play a key role in developing novel therapeutic strategies for patients with chronic obstructive pulmonary disease (COPD) if they can be shown to accurately represent the pathophysiological characteristics of individual patients. Methods We evaluated the capability of a computational simulator to reproduce the heterogeneous effects of COPD on alveolar mechanics as captured in a number of different patient datasets. Results Our results show that accurately representing the pathophysiology of individual COPD patients necessitates the use of simulation models with large numbers (up to 200) of compartments for gas exchange. The tuning of such complex simulation models ‘by hand’ to match patient data is not feasible, and thus we present an automated approach based on the use of global optimization algorithms and high-performance computing. Using this approach, we are able to achieve extremely close matches between the simulator and a range of patient data including PaO2, PaCO2, pulmonary deadspace fraction, pulmonary shunt fraction, and ventilation/perfusion (V̇/Q) curves. Using the simulator, we computed combinations of ventilator settings that optimally manage the trade-off between ensuring adequate gas exchange and minimizing the risk of ventilator-associated lung injury for an individual COPD patient. Conclusions Our results significantly strengthen the credibility of computer simulation models as research tools for the development of novel management protocols in COPD and other pulmonary disease states.

Introduction Direct comparison of the relative efficacy of different recruitment maneuvers (RMs) for patients with acute respiratory distress syndrome (ARDS) via clinical trials is difficult, due to the heterogeneity of patient populations and disease states, as well as a variety of practical issues. There is also significant uncertainty regarding the minimum values of positive end-expiratory pressure (PEEP) required to ensure maintenance of effective lung recruitment using RMs. We used patient-specific computational simulation to analyze how three different RMs act to improve physiological responses, and investigate how different levels of PEEP contribute to maintaining effective lung recruitment. Methods We conducted experiments on five ‘virtual’ ARDS patients using a computational simulator that reproduces static and dynamic features of a multivariable clinical dataset on the responses of individual ARDS patients to a range of ventilator inputs. Three recruitment maneuvers (sustained inflation (SI), maximal recruitment strategy (MRS) followed by a titrated PEEP, and prolonged recruitment maneuver (PRM)) were implemented and evaluated for a range of different pressure settings. Results All maneuvers demonstrated improvements in gas exchange, but the extent and duration of improvement varied significantly, as did the observed mechanism of operation. Maintaining adequate post-RM levels of PEEP was seen to be crucial in avoiding cliff-edge type re-collapse of alveolar units for all maneuvers. For all five patients, the MRS exhibited the most prolonged improvement in oxygenation, and we found that a PEEP setting of 35 cm H2O with a fixed driving pressure of 15 cm H2O (above PEEP) was sufficient to achieve 95% recruitment. Subsequently, we found that PEEP titrated to a value of 16 cm H2O was able to maintain 95% recruitment in all five patients. Conclusions There appears to be significant scope for reducing the peak levels of PEEP originally specified in the MRS and hence to avoid exposing the lung to unnecessarily high pressures. More generally, our study highlights the huge potential of computer simulation to assist in evaluating the efficacy of different recruitment maneuvers, in understanding their modes of operation, in optimizing RMs for individual patients, and in supporting clinicians in the rational design of improved treatment strategies.

Background A recent prospective trial using porcine models of severe acute respiratory distress syndrome (ARDS) indicated that positive-pressure ventilation delivered by a conventional intensive care ventilator at a moderately high frequency allows safe reduction of tidal volume below 6 ml/kg, leading to more protective ventilation. We aimed to explore whether these results would be replicated when implementing similar ventilation strategies in a high-fidelity computational simulator, tuned to match data on the responses of a number of human ARDS patients to different ventilator inputs. Methods We evaluated three different strategies for managing the trade-off between increasing respiratory rate and reducing tidal volume while attempting to maintain the partial pressure of carbon dioxide in arterial blood (PaCO2) constant on a computational simulator configured with ARDS patient datasets. Results For a fixed sequence of stepwise increases in the respiratory rate, corresponding decreases in tidal volume to keep the alveolar minute ventilation and inspiratory flow constant were calculated according to standard formulae. When applied on the simulator, however, these sequences of ventilator settings failed to maintain PaCO2 adequately in the virtual patients considered. In contrast, an approach based on combining numerical optimisation methods with computational simulation allowed a sequence of tidal volume reductions to be computed for each virtual patient that maintained PaCO2 levels while significantly reducing peak airway pressures and dynamic alveolar strain in all patients. Conclusions Our study supports the proposition that moderately high-frequency respiratory rates can allow more protective ventilation of ARDS patients and highlights the potential role of high-fidelity simulators in computing optimised and personalised ventilator settings for individual patients using this approach. Electronic supplementary material The online version of this article (doi:10.1186/s40635-015-0068-8) contains supplementary material, which is available to authorized users.