Personalised treatment of acute respiratory distress syndrome

This thesis describes personalised treatment of acute respiratory distress syndrome based on biomarkers and recruitability. In part 1, biomarkers, we aim to titrate the use of corticosteroids. In part 2, recruitability, we titrate PEEP using electrical impedance tomography

Personalised treatment of acute respiratory distress syndrome

This thesis describes personalised treatment of acute respiratory distress syndrome based on biomarkers and recruitability. In part 1, biomarkers, we aim to titrate the use of corticosteroids. In part 2, recruitability, we titrate PEEP using electrical impedance tomography

Model based PEEP titration versus standard practice in mechanical ventilation: A randomised controlled trial

Background: Positive end-expiratory pressure (PEEP) at minimum respiratory elastance during mechanical ventilation (MV) in patients with acute respiratory distress syndrome (ARDS) may improve patient care and outcome. The Clinical utilisation of respiratory elastance (CURE) trial is a two-arm, randomised controlled trial (RCT) investigating the performance of PEEP selected at an objective, model-based minimal respiratory system elastance in patients with ARDS. Methods and design: The CURE RCT compares two groups of patients requiring invasive MV with a partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio ≤ 200; one criterion of the Berlin consensus definition of moderate (≤ 200) or severe (≤ 100) ARDS. All patients are ventilated using pressure controlled (bi-level) ventilation with tidal volume = 6-8 ml/kg. Patients randomised to the control group will have PEEP selected per standard practice (SPV). Patients randomised to the intervention will have PEEP selected based on a minimal elastance using a model-based computerised method. The CURE RCT is a single-centre trial in the intensive care unit (ICU) of Christchurch hospital, New Zealand, with a target sample size of 320 patients over a maximum of 3 years. The primary outcome is the area under the curve (AUC) ratio of arterial blood oxygenation to the fraction of inspired oxygen over time. Secondary outcomes include length of time of MV, ventilator-free days (VFD) up to 28 days, ICU and hospital length of stay, AUC of oxygen saturation (SpO )/FiO during MV, number of desaturation events (SpO < 88%), changes in respiratory mechanics and chest x-ray index scores, rescue therapies (prone positioning, nitric oxide use, extracorporeal membrane oxygenation) and hospital and 90-day mortality. Discussion: The CURE RCT is the first trial comparing significant clinical outcomes in patients with ARDS in whom PEEP is selected at minimum elastance using an objective model-based method able to quantify and consider both inter-patient and intra-patient variability. CURE aims to demonstrate the hypothesized benefit of patient-specific PEEP and attest to the significance of real-time monitoring and decision-support for MV in the critical care environment. Trial registration: Australian New Zealand Clinical Trial Registry, ACTRN12614001069640. Registered on 22 September 2014. (https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366838&isReview=true) The CURE RCT clinical protocol and data usage has been granted by the New Zealand South Regional Ethics Committee (Reference number: 14/STH/132). 2 2

Towards respiratory muscle-protective mechanical ventilation in the critically ill: technology to monitor and assist physiology

Inadequate delivery of ventilatory assist and unphysiological respiratory drive may severely worsen respiratory muscle function in mechanically ventilated critically ill patients. Diaphragm weakness in these patients is exceedingly common (>60% of patients) and associated with poor clinical outcomes, including difficult ventilator liberation, increased risks of intensive care unit (ICU) and hospital readmission, and mortality. The underlying mechanisms of diaphragm dysfunction were extensively discussed in this thesis. Pathways primarily include the development of diaphragm disuse atrophy due to muscle inactivity or low respiratory drive (strong clinical evidence), and diaphragm injury as a result of excessive breathing effort due to insufficient ventilator assist or excessive respiratory drive (moderate evidence, mostly from experimental work). Excessive breathing effort may also worsen lung injury through pathways that include high lung stress and strain, pendelluft, increased lung perfusion, and patient-ventilator dyssynchrony. Relatively little attention has been paid to the effects of critical illness and mechanical ventilation on the expiratory muscles; however, dysfunction of these muscles has been linked to inadequate central airway clearance and extubation failure. The motivation for performing the work presented in this thesis was the hypothesis that maintaining physiological levels of respiratory muscle activity under mechanical ventilation could prevent or attenuate the development respiratory muscle weakness, and hence, improve patient outcomes. This strategy, integrated with lung-protective ventilation, was recently proposed by international experts from different professional societies (this thesis), and is referred to as a combined lung and diaphragm-protective ventilation approach. Today, an important barrier for implementing and evaluating such an approach is the lack of feasible, reliable and well-understood modalities to assess breathing effort at the bedside, as well as strategies for assisting and restoring respiratory muscle function during mechanical ventilation. Furthermore, monitoring breathing effort is crucial to identify potential relationships between patient management and detrimental respiratory (muscle) function that can be targeted to improve clinical outcomes. In this thesis we identified and improved monitoring modalities for the diaphragm (Part I), we investigated the impact of mechanical ventilation on the respiratory pump, especially the diaphragm (Part II), and we evaluated a novel strategy for maintaining expiratory muscle activity under mechanical ventilation (Part III)

Mechanical Ventilation

Mechanical ventilation, ventilator management, and weaning from mechanical ventilation vary based on location within the hospital, type of lung injury, and medical condition of the patient. Understanding the types of lung injury and various methods of achieving ventilation expand the armamentarium of the practitioner and allow for the best management decisions. This book begins with the use of a high-flow nasal cannula (HFNC) and a detailed description of the advanced modes of ventilation. The information on the types of ventilation can then be applied to the ventilation approaches in different populations of patients: the trauma patients, the obese patients, and the patients under neurocritical care. The conclusion contains a discussion of the mechanisms on how to wean from mechanical ventilation and how certain medical conditions affect the weaning process

Next-generation, personalised, model-based critical care medicine : a state-of-the art review of in silico virtual patient models, methods, and cohorts, and how to validation them

© 2018 The Author(s). Critical care, like many healthcare areas, is under a dual assault from significantly increasing demographic and economic pressures. Intensive care unit (ICU) patients are highly variable in response to treatment, and increasingly aging populations mean ICUs are under increasing demand and their cohorts are increasingly ill. Equally, patient expectations are growing, while the economic ability to deliver care to all is declining. Better, more productive care is thus the big challenge. One means to that end is personalised care designed to manage the significant inter- and intra-patient variability that makes the ICU patient difficult. Thus, moving from current "one size fits all" protocolised care to adaptive, model-based "one method fits all" personalised care could deliver the required step change in the quality, and simultaneously the productivity and cost, of care. Computer models of human physiology are a unique tool to personalise care, as they can couple clinical data with mathematical methods to create subject-specific models and virtual patients to design new, personalised and more optimal protocols, as well as to guide care in real-time. They rely on identifying time varying patient-specific parameters in the model that capture inter- and intra-patient variability, the difference between patients and the evolution of patient condition. Properly validated, virtual patients represent the real patients, and can be used in silico to test different protocols or interventions, or in real-time to guide care. Hence, the underlying models and methods create the foundation for next generation care, as well as a tool for safely and rapidly developing personalised treatment protocols over large virtual cohorts using virtual trials. This review examines the models and methods used to create virtual patients. Specifically, it presents the models types and structures used and the data required. It then covers how to validate the resulting virtual patients and trials, and how these virtual trials can help design and optimise clinical trial. Links between these models and higher order, more complex physiome models are also discussed. In each section, it explores the progress reported up to date, especially on core ICU therapies in glycemic, circulatory and mechanical ventilation management, where high cost and frequency of occurrence provide a significant opportunity for model-based methods to have measurable clinical and economic impact. The outcomes are readily generalised to other areas of medical care

Effect of individualized positive end-expiratory pressure based on electrical impedance tomography guidance on pulmonary ventilation distribution in patients who receive abdominal thermal perfusion chemotherapy

BackgroundElectrical impedance tomography (EIT) has been shown to be useful in guiding individual positive end-expiratory pressure titration for patients with mechanical ventilation. However, the appropriate positive end-expiratory pressure (PEEP) level and whether the individualized PEEP needs to be adjusted during long-term surgery (&gt;6 h) were unknown. Meanwhile, the effect of individualized PEEP on the distribution of pulmonary ventilation in patients who receive abdominal thermoperfusion chemotherapy is unknown. The primary aim of this study was to observe the effect of EIT-guided PEEP on the distribution of pulmonary ventilation in patients undergoing cytoreductive surgery (CRS) combined with hot intraperitoneal chemotherapy (HIPEC). The secondary aim was to analyze their effect on postoperative pulmonary complications.MethodsA total of 48 patients were recruited and randomly divided into two groups, with 24 patients in each group. For the control group (group A), PEEP was set at 5 cm H2O, while in the EIT group (group B), individual PEEP was titrated and adjusted every 2 h with EIT guidance. Ventilation distribution, respiratory/circulation parameters, and PPC incidence were compared between the two groups.ResultsThe average individualized PEEP was 10.3 ± 1.5 cm H2O, 10.2 ± 1.6 cm H2O, 10.1 ± 1.8 cm H2O, and 9.7 ± 2.1 cm H2O at 5 min, 2 h, 4 h, and 6 h after tracheal intubation during CRS + HIPEC. Individualized PEEP was correlated with ventilation distribution in the regions of interest (ROI) 1 and ROI 3 at 4 h mechanical ventilation and ROI 1 at 6 h mechanical ventilation. The ventilation distribution under individualized PEEP was back-shifted for 6 h but moved to the control group’s ventral side under PEEP 5 cm H2O. The respiratory and circulatory function indicators were both acceptable either under individualized PEEP or PEEP 5 cm H2O. The incidence of total PPCs was significantly lower under individualized PEEP (66.7%) than PEEP 5 cm H2O (37.5%) for patients with CRS + HIPEC.ConclusionThe appropriate individualized PEEP was stable at approximately 10 cm H2O during 6 h for patients with CRS + HIPEC, along with better ventilation distribution and a lower total PPC incidence than the fixed PEEP of 5 cm H2O.Clinical trial registration: identifier ChiCTR1900023897