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Patient-maintained propofol sedation (PMPS) is the delivery of procedural propofol sedation by target-controlled infusion with the patient exerting an element of control over their target-site propofol concentration. This scoping review aims to establish the extent and nature of current knowledge regarding PMPS from both a clinical and technological perspective, thereby identifying knowledge gaps to guide future research. We searched MEDLINE, EMBASE, and OpenGrey databases, identifying 17 clinical studies for analysis. PMPS is described in the context of healthy volunteers and in orthopaedic, general surgical, dental, and endoscopic clinical settings. All studies used modifications to existing commercially-available infusion devices to achieve prototype systems capable of PMPS. The current literature precludes rigorous generalisable conclusions regarding the safety or comparative clinical effectiveness of PMPS, however cautious acknowledgement of efficacy in specific clinical settings is appropriate. Based on the existing literature, together with new standardised outcome reporting recommendations for sedation research and frameworks designed to assess novel health technologies research, we have made recommendations for future pharmacological, clinical, behavioural, and health economic research on PMPS. We conclude that high-quality experimental clinical trials with relevant comparator groups assessing the impact of PMPS on standardised patient-orientated outcome measures are urgently required. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article looks at the types, incidence, causes, effects, management and avoidance of intraoperative awareness during anaesthesia. It describes the two types of intraoperative awareness, the explicit memory and implicit memory. The authors note that the psychological effects of intraoperative awareness are post-traumatic stress disorder (PTSD), insomnia, anxiety and depression. It explores the required dosage of anaesthetics based on age and effects of over- and under-dosage on awareness.

Joseph Priestley, a chemist and Presbyterian minister, discovered nitrous oxide in 1772.1 Its analgesic action was subsequently described in 1800 by Humphrey Davy. Towards the end of the nineteenth century, its anaesthetic properties were recorded under hyperbaric conditions by Paul Bert. Applications for the use of nitrous oxide have developed greatly since that time. It has widespread use in anaesthesia but has many other uses; examples include its use as an aerosol propellant in whipped cream dispensers and for enhancement of engine performance in drag-racing. [ABSTRACT FROM AUTHOR]

: BackgroundAlthough mesenteric angiography and embolization are established radiologic procedures, the evidence-base to aid decision making regarding selection of these procedures in the emergent situation in patients with hemorrhagic complications of pancreatitis is limited.: MethodsA retrospective analysis of 19 patients with hemorrhagic complications of pancreatic inflammatory disease (acute pancreatitis, chronic pancreatitis, and pseudocyst) referred over a 4-year period and identified at the point of mesenteric angiography in order to determine the influence of interventional radiologic maneuvers on outcome.: ResultsMesenteric angiography localized bleeding in 15 (79%), with 11 (58%) embolizations undertaken. There was one (9%) procedure-related complication and 3 (27%) rebleeds. Of 11 patients undergoing embolization, 8 (73%) required no further intervention for bleeding and 8 (73%) survived.: ConclusionsMesenteric angiography is valuable in localizing bleeding in patients with major vascular complications of pancreatic inflammatory disease. Angiographic embolization can achieve definitive hemostasis and stabilize a critically ill patient to permit disease reappraisal. [Copyright &y& Elsevier]

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]

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. [ABSTRACT FROM AUTHOR]

The authors raise issue on the urgent need to create guidelines for mechanical ventilation in paediatric acute respiratory distress syndrome (PARDS). They propose that analysis of a large PARDS data set using computational simulator would allow to determine the scope for safely implementing more protective ventilation. A description of four lung protective strategies that accurately reproduce patient data is provided.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The selection of mechanical ventilator settings that ensure adequate oxygenation and carbon dioxide clearance while minimizing the risk of ventilator-associated lung injury (VALI) is a significant challenge for intensive-care clinicians. Current guidelines are largely based on previous experience combined with recommendations from a limited number of in vivo studies whose data are typically more applicable to populations than to individuals suffering from particular diseases of the lung. By combining validated computational models of pulmonary pathophysiology with global optimization algorithms, we generate in silico experiments to examine current practice and uncover optimal combinations of ventilator settings for individual patient and disease states. Formulating the problem as a multiobjective, multivariable constrained optimization problem, we compute settings of tidal volume, ventilation rate, inspiratory/expiratory ratio, positive end-expiratory pressure and inspired fraction of oxygen that optimally manage the tradeoffs between ensuring adequate oxygenation and carbon dioxide clearance and minimizing the risk of VALI for different pulmonary disease scenarios. [ABSTRACT FROM PUBLISHER]

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. [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: 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. [ABSTRACT FROM AUTHOR]

Background: The effect of mental rotation training on ultrasound-guided regional anaesthesia (UGRA) skill acquisition is currently unknown. In this study we aimed to examine whether mental rotation skill training can improve UGRA task performance by novice operators.Methods: We enrolled 94 volunteers with no prior experience of UGRA in this randomised controlled study. After a baseline mental rotation test, their performance in a standardised UGRA needling task was independently assessed by two raters using the composite error score (CES) and global rating scale (GRS). Volunteers with low baseline mental rotation ability were randomised to a mental rotation training group or a no training group, and the UGRA needling task was repeated to determine the impact of the training intervention on task performance. The study primary outcome measure was UGRA needling task CES measured before and after the training intervention.Results: Multivariate analyses controlling for age, gender, and previous performance showed that participants exposed to the training intervention made significantly fewer errors (CES B=-0.66 [standard error, se=0.17]; P<0.001; 95% confidence interval [CI], -0.92 to -0.26) and displayed improved overall performance (GRS B=6.15 [se=2.99], P=0.048, 95% CI=0.06 to 12.13) when undertaking the UGRA needling task.Conclusions: A simple training intervention, based on the manipulation and rotation of three-dimensional models, results in improved technical performance of a UGRA needling task in operators with low baseline mental rotation skills. [ABSTRACT FROM AUTHOR]

Objectives: Mechanical power and driving pressure have been proposed as indicators, and possibly drivers, of ventilator-induced lung injury. We tested the utility of these different measures as targets to derive maximally protective ventilator settings.Design: A high-fidelity computational simulator was matched to individual patient data and used to identify strategies that minimize driving pressure, mechanical power, and a modified mechanical power that removes the direct linear, positive dependence between mechanical power and positive end-expiratory pressure.Setting: Interdisciplinary Collaboration in Systems Medicine Research Network.Subjects: Data were collected from a prospective observational cohort of pediatric acute respiratory distress syndrome from the Children's Hospital of Philadelphia (n = 77) and from the low tidal volume arm of the Acute Respiratory Distress Syndrome Network tidal volume trial (n = 100).Interventions: Global optimization algorithms evaluated more than 26.7 million changes to ventilator settings (approximately 150,000 per patient) to identify strategies that minimize driving pressure, mechanical power, or modified mechanical power.Measurements and Main Results: Large average reductions in driving pressure (pediatric: 23%, adult: 23%), mechanical power (pediatric: 44%, adult: 66%), and modified mechanical power (pediatric: 61%, adult: 67%) were achievable in both cohorts when oxygenation and ventilation were allowed to vary within prespecified ranges. Reductions in driving pressure (pediatric: 12%, adult: 2%), mechanical power (pediatric: 24%, adult: 46%), and modified mechanical power (pediatric: 44%, adult: 46%) were achievable even when no deterioration in gas exchange was allowed. Minimization of mechanical power and modified mechanical power was achieved by increasing tidal volume and decreasing respiratory rate. In the pediatric cohort, minimum driving pressure was achieved by reducing tidal volume and increasing respiratory rate and positive end-expiratory pressure. The Acute Respiratory Distress Syndrome Network dataset had limited scope for further reducing tidal volume, but driving pressure was still significantly reduced by increasing positive end-expiratory pressure.Conclusions: Our analysis identified different strategies that minimized driving pressure or mechanical power consistently across pediatric and adult datasets. Minimizing standard and alternative formulations of mechanical power led to significant increases in tidal volume. Targeting driving pressure for minimization resulted in ventilator settings that also reduced mechanical power and modified mechanical power, but not vice versa. [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]

Background: Primary blast lung injury (PBLI) presents as a syndrome of respiratory distress and haemoptysis resulting from explosive shock wave exposure and is a frequent cause of mortality and morbidity in both military conflicts and terrorist attacks. The optimal mode of mechanical ventilation for managing PBLI is not currently known, and clinical trials in humans are impossible due to the sporadic and violent nature of the disease. Methods: A high-fidelity multi-organ computational simulator of PBLI pathophysiology was configured to replicate data from 14 PBLI casualties from the conflict in Afghanistan. Adaptive and responsive ventilatory protocols implementing low tidal volume (LTV) ventilation and airway pressure release ventilation (APRV) were applied to each simulated patient for 24 h, allowing direct quantitative comparison of their effects on gas exchange, ventilatory parameters, haemodynamics, extravascular lung water and indices of ventilator-induced lung injury. Results: The simulated patients responded well to both ventilation strategies. Post 24-h investigation period, the APRV arm had similar PF ratios (137 mmHg vs 157 mmHg), lower sub-injury threshold levels of mechanical power (11.9 J/min vs 20.7 J/min) and lower levels of extravascular lung water (501 ml vs 600 ml) compared to conventional LTV. Driving pressure was higher in the APRV group (11.9 cmH2O vs 8.6 cmH2O), but still significantly less than levels associated with increased mortality. Conclusions: Appropriate use of APRV may offer casualties with PBLI important mortality-related benefits and should be considered for management of this challenging patient group. [ABSTRACT FROM AUTHOR]

Background: Recent data suggest that beta blockers are associated with increased perioperative risk in hypertensive patients. We investigated whether beta blockers were associated with an increased risk in elderly patients with raised preoperative arterial blood pressure.Methods: We conducted a propensity-score-matched cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13), including 84 633 patients aged 65 yr or over. Conditional logistic regression models, including factors that were significantly associated with the outcome, were constructed for 30-day mortality after elective noncardiac surgery. The effects of beta blockers (primary outcome), renin-angiotensin system (RAS) inhibitors, calcium-channel blockers, thiazides, loop diuretics, and statins were investigated at systolic and diastolic arterial pressure thresholds.Results: Beta blockers were associated with increased odds of postoperative 30-day mortality in patients with systolic hypertension (defined as systolic BP >140 mm Hg; adjusted odds ratio [aOR]: 1.92; 95% confidence interval [CI]: 1.05-3.51). After excluding patients for whom prior data suggest benefit from perioperative beta blockade (patients with prior myocardial infarction or heart failure), rather than adjusting for them, the point estimate shifted slightly (aOR: 2.06; 95% CI: 1.09-3.89). Compared with no use, statins (aOR: 0.35; 95% CI: 0.17-0.75) and thiazides (aOR: 0.28; 95% CI: 0.10-0.78) were associated with lower mortality in patients with systolic hypertension.Conclusions: These data suggest that the safety of perioperative beta blockers may be influenced by preoperative blood pressure thresholds. A randomised controlled trial of beta-blocker withdrawal, in select populations, is required to identify a causal relationship. [ABSTRACT FROM AUTHOR]

Background: Recent analyses of patient data in acute respiratory distress syndrome (ARDS) showed that a lower ventilator driving pressure was associated with reduced relative risk of mortality. These findings await full validation in prospective clinical trials.Methods: To investigate the association between driving pressures and ventilator induced lung injury (VILI), we calibrated a high fidelity computational simulator of cardiopulmonary pathophysiology against a clinical dataset, capturing the responses to changes in mechanical ventilation of 25 adult ARDS patients. Each of these in silico patients was subjected to the same range of values of driving pressure and positive end expiratory pressure (PEEP) used in the previous analyses of clinical trial data. The resulting effects on several physiological variables and proposed indices of VILI were computed and compared with data relating ventilator settings with relative risk of death.Results: Three VILI indices: dynamic strain, mechanical power and tidal recruitment, showed a strong correlation with the reported relative risk of death across all ranges of driving pressures and PEEP. Other variables, such as alveolar pressure, oxygen delivery and lung compliance, correlated poorly with the data on relative risk of death.Conclusions: Our results suggest a credible mechanistic explanation for the proposed association between driving pressure and relative risk of death. While dynamic strain and tidal recruitment are difficult to measure routinely in patients, the easily computed VILI indicator known as mechanical power also showed a strong correlation with mortality risk, highlighting its potential usefulness in designing more protective ventilation strategies for this patient group. [ABSTRACT FROM AUTHOR]

This study uses a highly fidelity computational simulator of pulmonary physiology to evaluate the impact of a soluble guanylate cyclase (sGC) modulator on gas exchange in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) as a complication. Three virtual patients with COPD were configured in the simulator based on clinical data. In agreement with previous clinical studies, modeling systemic application of an sGC modulator results in reduced partial pressure of oxygen (PaO2) and increased partial pressure of carbon dioxide (PaCO2) in arterial blood, if a drug‐induced reduction of pulmonary vascular resistance (PVR) equal to that observed experimentally is assumed. In contrast, for administration via dry powder inhalation (DPI), our simulations suggest that the treatment results in no deterioration in oxygenation. For patients under exercise, DPI administration lowers PH, whereas oxygenation is improved with respect to baseline values. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: Visuospatial ability correlates positively with novice performance of simple laparoscopic tasks. The aims of this study were to identify whether visuospatial ability could predict technical performance of an ultrasound-guided needle task by novice operators and to describe how emotional state, intelligence, and fear of failure impact on this.Methods: Sixty medical student volunteers enrolled in this observational study. The authors used an instructional video to standardize training for ultrasound-guided needle advancement in a turkey breast model and assessed volunteers' performance independently by two assessors using composite error score (CES) and global rating scale (GRS). The authors assessed their "visuospatial ability" with mental rotation test (MRT), group embedded figures test, and Alice Heim group ability test. Emotional state was judged with UWIST Mood Adjective Checklist (UMACL), and fear of failure and general cognitive ability were judged with numerical reasoning test.Results: High CES scores (high error rate) were associated with low MRT scores (ρ = -0.54; P < 0.001). Better GRS scores were associated with better MRT scores (ρ = 0.47; P < 0.001). Regarding emotions, GRS scores were low when anxiety levels were high (ρ = -0.35; P = 0.005) and CES scores (errors) were low when individuals reported feeling vigorous and active (ρ = -0.30; P = 0.01).Conclusions: An MRT predicts novice performance of an ultrasound-guided needling task on a turkey model and as a trait measure could be used as a tool to focus training resources on less-able individuals. Anxiety adversely affects performance. Therefore, both may prove useful in directing targeted training in ultrasound-guided regional anesthesia. [ABSTRACT FROM AUTHOR]

Background: Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. Methods: We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline. Results: Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p=0.33) or any secondary end point of organ dysfunction or patient outcome. Conclusions: This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study. [ABSTRACT FROM AUTHOR]

Background: The clinical efficacy of effect-site targeted patient-maintained propofol sedation (PMPS) compared to anaesthetist-controlled propofol sedation (ACPS) for patients undergoing awake joint replacement surgery is currently unknown. There is no commercially available medical device capable of delivering PMPS so we have designed and built such a device. We plan a clinical trial to compare PMPS to ACPS and to collect data relating to the safety of our prototype device in delivering sedation.Methods: The trial is an open-label, randomised, controlled superiority trial recruiting adults who are undergoing elective primary lower-limb arthroplasty with sedation by propofol infusion by effect-site targeting into two equal-sized parallel arms: PMPS and ACPS. The primary research objective is to compare the body-weight-normalised rate of propofol consumption when sedation for surgery on adults undergoing elective primary lower-limb arthroplasty under spinal anaesthesia is patient-maintained versus when it is anaesthetist-controlled. The study primary null hypothesis is that there is no difference in the rate of propofol consumption when sedation is patient-maintained versus anaesthetist-controlled.Discussion: This is the first trial to test the superiority of effect-site-targeted patient-maintained propofol sedation versus anaesthetist-controlled propofol sedation in terms of total propofol consumption during the sedation period. The results of this trial will help inform clinicians and device manufacturers of the clinical efficacy and safety of patient-maintained propofol sedation applied to a common operative setting.Trial Registration: International Standard Randomised Controlled Trial Number Registry, ISRCTN29129799 . Prospectively registered on 12 June 2018. [ABSTRACT FROM AUTHOR]