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In 2021 NHS England commissioned regional Adult Critical Care Transfer Services. These services will replace a historically predominant ad hoc approach to adult critical care transfers nationally. It is anticipated that these new formal services will provide a system of robust regional & national governance previously acknowledged to be deficient. As part of this process, it is important that an agreed set of transfer service quality indicators are developed to drive equitable improvement in patient care. We used a Delphi technique to develop a set of key performance indicators through consensus for a recently established London critical care transfer service. We believe this may be the first-time key performance indicators have been developed for adult critical care transfer services using a consensus method. We hope services will consider tracking similar measures to enable benchmarking and drive improvements in patient care.

Introduction Designated cross-specialty shock teams have been proposed as a mechanism to manage the complexity of decision-making and facilitate collaborative, patient-centred care-planning in cardiogenic shock. Observational data support the notion that shock protocols and teams may improve survival, but there is an absence of data interrogating how clinicians engage with and value the shock team paradigm. This study sought to explore clinician perceptions of the value of the shock call system on decision making and the management of CGS. Materials & methods A descriptive qualitative approach was used. A focus group, semi-structured interview was conducted with twelve cross-specialty members of a shock team at a single tertiary cardiac centre in the UK. The focus group was audio-recorded, transcribed, and thematically analysed to capture and describe the clinicians' experience and perceptions of shock team discussions. Results Eight cardiac intensivists, two heart failure cardiologists, one cardiothoracic surgeon and one interventional cardiologist participated in the focus group. Four key themes were identified from the discussions: supportive decision making; team communication; governance and learning; and future directions. Conclusion This study supports the notion that cross-specialty, real-time patient discussion may provide added value beyond protocolised decision making and account for the complexities of managing patients in a field where definitive, high-quality evidence to guide practice is currently limited.

In 2013, a group of clinicians on behalf of the National Institute for Health Research, collaborated with ICU Steps to produce guidance about people being enrolled in more than one critical care trial. This is referred to as “co-enrolment” and can be where a person takes part in one study at the same time as another study (or one after the other in a short time-frame). For instance, being part of a study looking at sepsis drugs and a mechanical ventilation weaning study. The drivers for developing this guidance were a lack of any existing guidance, nationally and internationally, at that time, and a desire to ensure high quality research is conducted. The emphasis was on making trials as safe as possible for patients and ensuring robust trial outcomes. Critical care was seen to lead in this, with our exemplar guidance used across all health research. We wish to revisit this guidance now that there is more experience of coenrolment in critical care trials. There is also more awareness of different consent models, such as deferred consent (taking consent when a person is awake and able to give consent) and consultee consent (asking families or independent professionals to consent). Consenting to coenrolment is an important ethical consideration for the revision of this guidance.

Introduction The probability of surviving a cardiac arrest remains low. International resuscitation guidelines state that extracorporeal cardiopulmonary resuscitation (ECPR) may have a role in selected patients suffering refractory cardiac arrest. Identifying these patients is challenging. This project systematically reviewed the evidence comparing the outcomes of ECPR over conventional-CPR (CCPR), before examining resuscitation-specific parameters to assess which patients might benefit from ECPR. Method Literature searches of studies comparing ECPR to CCPR and the clinical parameters of survivors of ECPR were performed. The primary outcome examined was survival at hospital discharge or 30 days. A secondary analysis examined the resuscitation parameters that may be associated with survival in patients who receive ECPR (no-flow and low-flow intervals, bystander-CPR, initial shockable cardiac rhythm, and witnessed cardiac arrest). Results Seventeen of 948 examined studies were included. ECPR demonstrated improved survival (OR 0.40 (0.27–0.60)) and a better neurological outcome (OR 0.10 (0.04–0.27)) over CCPR during literature review and meta-analysis. Characteristics that were associated with improved survival in patients receiving ECPR included an initial shockable rhythm and a shorter low-flow time. Shorter no-flow, the presence of bystander-CPR and witnessed arrests were not characteristics that were associated with improved survival following meta-analysis, although the quality of input data was low. All data were non-randomised, and hence the potential for bias is high. Conclusion ECPR is a sophisticated treatment option which may improve outcomes in a selected patient population in refractory cardiac arrest. Further comparative research is needed clarify the role of this potential resuscitative therapy.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary support primarily used in cardiothoracic and intensive care unit (ICU) settings. The purpose of this review is to familiarise radiologists with the imaging features of ECMO devices, their associated complications and appropriate imaging protocols for contrast-enhanced CT imaging of ECMO patients. This paper will provide a brief introduction to ECMO and the imaging modalities utilised in ECMO patients, followed by a description of the types of ECMO available and cannula positioning. Indications and contraindications for ECMO will be outlined followed by a description of the complications associated with ECMO, which radiologists should recognise. Finally, the imaging protocol and interpretation of contrast-enhanced CT imaging in ECMO patients will be discussed. In the current clinical climate with millions of COVID-19 cases around the world and tens of thousands of critically ill patients, many requiring cardiopulmonary support in intensive care units, the use of ECMO in adults has increased, and thus so has the volume of imaging. Radiologists need to be familiar with the types of ECMO available, the correct positioning of the catheters depending on the type of ECMO being utilised, and the associated complications and imaging artefacts.

Disclaimer: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being deployed for selected patients in cardiac arrest who do not attain a native circulation with conventional CPR (ECPR). This ELSO guideline is intended to be a practical guide to implementing ECPR and the early management following establishment of ECMO support. Where a paucity of high-quality evidence exists, a consensus has been reached amongst the authors to provide guidance to the clinician. This guideline will be updated as further evidence in this field becomes available.

Background Out-of-hospital cardiac arrest carries a poor prognosis with survival less than 10% in many patient cohorts. Survival is inversely associated with duration of resuscitation as external chest compressions do not provide sufficient blood flow to prevent irreversible organ damage during a prolonged resuscitation. Extracorporeal membrane oxygenation (ECMO) instituted during cardiac arrest can provide normal physiological blood flows and is termed Extracorporeal Cardio-Pulmonary Resuscitation (ECPR). ECPR may improve survival when used with in-hospital cardiac arrests. This possible survival benefit has not been replicated in trials of out-of-hospital cardiac arrests, possibly because of the additional time it takes to transport the patient to hospital and initiate ECPR. Pre-hospital ECPR may shorten the time between cardiac arrest and physiological blood flows, potentially improving survival. It may also mitigate some of the neurological injury that many survivors suffer. Methods Sub30 is a prospective six patient feasibility study. The primary aim is to test whether it is possible to institute ECPR within 30 ​min of collapse in adult patients with refractory out of hospital cardiac arrest (OHCA). The secondary aims are to gather preliminary data on clinical outcomes, resource utilisation, and health economics associated with rapid ECPR delivery in order to plan any subsequent clinical investigation or clinical service. On study days a dedicated fast-response vehicle with ECPR capability will be tasked to out-of-hospital cardiac arrests in an area of London served by Barts Heart Centre. If patients suffer a cardiac arrest refractory to standard advanced resuscitation and meet eligibility criteria, ECPR will be started in the pre-hospital environment. Discussion Delivering pre-hospital ECPR within 30 ​min of an out-of-hospital cardiac arrest presents significant ethical, clinical, governance and logistical challenges. Prior to conducting an efficacy study of ECPR the feasibility of timely and safe application must be demonstrated first. Extensive planning, multiple high-fidelity multiagency simulations and a unique collaboration between pre-hospital and in-hospital institutions will allow us to test the feasibility of this intervention in London. The study has been reviewed, refined and endorsed by the International ECMO Network (ECMONet). Trial registration Clinicaltrials. gov NCT03700125 , prospectively registered October 9, 2018.

A 43-year-old man with Austrian syndrome, the triad of infective endocarditis (IE), pneumonia and meningitis caused by Streptococcus pneumoniae, underwent emergency aortic and mitral valve replacement and closure of an aortic root abscess. Postoperatively, he required mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation and an intra-aortic balloon pump. Several days after surgery, new mitral and aortic paraprosthetic leaks (PPLs) developed. These were managed conservatively, initially, but eventually required percutaneous closure 6 weeks after the initial operation. This has enabled the patient to recover to independent mobility, 20 weeks after the operation. This case illustrates a rare clinical syndrome and the devastating impact of IE. Moreover, it illustrates the successful application of extracorporeal membrane oxygenation in postcardiotomy cardiac failure and the successful treatment of PPL in a patient unfit for redo surgery.

Introduction: Comprehensive clinical examination can be compromised in patients on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Adjunctive diagnostic imaging strategies range from bedside imaging only to routine computed tomography (CT). The risk-benefit of either approach remains to be evaluated. Patients retrieved to the Royal Brompton Hospital (RBH) on VV-ECMO routinely undergo admission CT imaging of head, chest, abdomen and pelvis. This study aimed to identify how frequently changes in therapy or adverse events could be attributed to routine CT scanning. Methods: Demographic and clinical data were gathered retrospectively from patients retrieved to RBH on VV-ECMO (January 2014-2016). Scans were categorized as ‘routine’ or requested to clarify a specific clinical uncertainty. Clinical records were reviewed to identify attributable management changes and CT- related adverse events. Seventy-two patients were retrieved on VV-ECMO (median age 44 years) and 65 scanned on admission (mean radiation dose 2344mGy-cm). Routine head CT head yielded novel clinical information in 11 patients, 10 of whom had unexpected intracranial haemorrhage and, subsequently, had their anticoagulation withheld. Routine thoracic CT identified unexpected positive findings in three patients (early fibrosis, pulmonary vasculitis, pneumomediastinum), eliciting management variation in one (steroid administration). Routine abdomen/pelvis CT identified new information in three patients (adrenal haemorrhage, hepatosteatosis, splenic infarction), changing the management in one (withholding anticoagulation). Results: CT scanning was not associated with consequential adverse events (e.g. accidental decannulation, gas entrainment into the circuit, hypoxia, hypotension). Median transfer/scan time was 78 minutes, requiring five ITU staff-members. In our cohort, a policy of routine head CT changed the management in 17% of patients; the yield from routine chest, abdomen and pelvis CT was modest. CT transfer was safe, but resource intensive. Conclusion: Prospective studies should evaluate whether routine CT impacts outcome.

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO2R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO2R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

Around 2% of adults have heart failure, and the prevalence increases with advancing ages. This may manifest chronically but also acutely. Cardiogenic shock is the most extreme manifestation of acute heart failure, manifesting as the rapid development of life-threatening tissue hypoperfusion and organ dysfunction. The causes and management of these heart failure syndromes are considered in this set of mini reviews with a focus on management of the precipitating etiology, specifically coronary artery disease. The importance of risk stratification and risk-based management strategies in pulmonary embolism as a cause of acute right ventricular failure is discussed. Mechanical support of the failing heart is possible with intra-aortic balloon pumps and ventricular assist devices. These can be used in acutely or chronically and their indications are reviewed herein. Finally, advances in cardiopulmonary resuscitation are considered. This review contains 3 figures, 3 tables, and 57 references. Key Words: cardiovascular system, cardiac tamponade, cardiogenic shock, cardiomyopathy, cardiopulmonary resuscitation, circulatory support, heart failure, mechanical pulmonary embolism

There is increasing interest in the potential use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in the prehospital setting to stabilise patients in refractory cardiac arrest.1 VA-ECMO involves draining blood through a cannula sited in a large vein and passing it through a pump and a membrane oxygenator before returning it under pressure through another cannula sited in a large artery. It can therefore be used to temporarily replace the function of the heart and lungs. When VA-ECMO is used to manage refractory cardiac arrest, it is termed extracorporeal cardiopulmonary resuscitation (ECPR). Out-of-hospital cardiac arrest patients have poor outcomes,2 3 not least because it takes time to package and transport them to heart attack centres. By bringing VA-ECMO into the prehospital environment, it is hoped that vital organ perfusion can be re-established more quickly in a refractory cardiac arrest, preventing irreversible hypoxic organ damage and potentially improving out-of-hospital cardiac arrest survival rates that remain very low. Prehospital ECPR is fraught with difficulties and potential complications,4 many of which can be prepared for by simulation. Unfortunately, there are no cost-effective, commercially available manikins designed for ECPR. Previous attempts at simulating prehospital ECPR have used separate manikins for the dichotomous elements of cardiopulmonary resuscitation (CPR) and extracorporeal membrane oxygenation (ECMO); however, this significantly reduces the fidelity of the exercise. In-hospital ECMO manikins often have to forego the use of …

In the intensive care unit (ICU), satisfaction with the care of their loved one impacts upon family members' psychological morbidity and maybe the health of patients afterwards. Enhancing family satisfaction is holistic and may impact on health throughout the hospital and beyond.

Background Debate remains regarding whether the systemic inflammatory response syndrome (SIRS) identifies patients with clinically important inflammation. Defining criteria may be disproportionately sensitive and lack specificity. We investigated the incidence and evolution of SIRS in a homogenous population (following cardiac surgery) over 7 days to establish the relationship between SIRS and outcome, modeling alternative permutations of the criteria to increase their discriminatory power for mortality, length of stay, and organ dysfunction. Methods We conducted a retrospective analysis of prospectively collected data from a cardiothoracic ICU. Consecutive patients requiring ICU admission for the first time after cardiac surgery (N = 2, 764) admitted over a 41-month period were studied. Results Concurrently, 96.2% of patients met the standard two criterion definition for SIRS within 24 h of ICU admission. Their mortality was 2.78%. By contrast, three or four criteria were more discriminatory of patients with higher mortality (4.21% and 10.2%, respectively). A test dataset suggested that meeting two criteria for at least 6 consecutive h may be the best model. This had a positive and negative predictive value of 7% and 99.5%, respectively, in a validation dataset. It performed well at predicting organ dysfunction and prolonged ICU admission. Conclusions The concept of SIRS remains valid following cardiac surgery. With suitable modification, its specificity can be improved significantly. We propose that meeting two or more defining criteria for 6 h could be used to define better populations with more difficult clinical courses following cardiac surgery. This group may merit a different clinical approach.

Purpose The epidemiology of acute kidney injury (AKI) after cardiac surgery depends on the definition used. Our aims were to evaluate the Risk/Injury/Failure/Loss/End-stage (RIFLE) criteria, the AKI Network (AKIN) classification, and the Kidney Disease: Improving Global Outcomes (KDIGO) classification for AKI post–cardiac surgery and to compare the outcome of patients on renal replacement therapy (RRT) with historical data. Methods Retrospective analysis of 1881 adults who had cardiac surgery between May 2006 and April 2008 and determination of the maximum AKI stage according to the AKIN, RIFLE, and KDIGO classifications. Results The incidence of AKI using the AKIN and RIFLE criteria was 25.9% and 24.9%, respectively, but individual patients were classified differently. The area under the receiver operating characteristic curve for hospital mortality was significantly higher using the AKIN compared with the RIFLE criteria (0.86 vs 0.78, P = .0009). Incidence and outcome of AKI according to the AKIN and KDIGO classification were identical. The percentage of patients who received RRT was 6.2% compared with 2.7% in 1989 to 1990. The associated hospital mortality fell from 82.9% in 1989 to 1990 to 15.6% in 2006 to 2008. Conclusions The AKIN classification correlated better with mortality than did the RIFLE criteria. Mortality of patients needing RRT after cardiac surgery has improved significantly during the last 20 years.

Background and objective Acute severe clinical deterioration of patients with cystic fibrosis (CF) may mandate endotracheal intubation. The benefits of intubation were evaluated by examining which pre-admission parameters were associated with intensive care unit (ICU) outcome and assessing the potential benefits of intubation for survivors in terms of time from ICU discharge to death. Methods A retrospective analysis of data from a single centre was undertaken. Results Thirty patients required intubation on 34 occasions (8 per 1000 admissions). Eleven patients died in ICU and 7 after ICU but not hospital discharge. Fifty-nine per cent of 22 patients intubated for pneumothorax and/or haemoptysis survived to hospital discharge. Of the twelve intubated for infective exacerbations, 33% survived to hospital discharge. Those who died after hospital discharge survived 447 days. There were no significant differences for survivors in reasons for intubation, colonizing organism, frequency of infective exacerbations, severity of illness or pulmonary physiology. Osteoporosis and a greater fall in body mass index over the 24 months prior were more frequent in non-survivors. Conclusions Patients with CF developing haemoptysis and/or pneumothorax should be admitted to ICU and intubated promptly, should this be required. Chronic disease markers may be more relevant prognostically than rates of hospitalization or forced expiratory volume in 1 s decline which should not be bars to invasive ventilation.

Extracorporeal carbon dioxide removal (ECCO2R) device technologies have enhanced the management of acute respiratory distress syndrome (ARDS) and other lung pathologies necessitating low tidal volume protective ventilation. We report the novel use of the interventional Lung Assist Membrane Ventilator® (iLA, Novalung GmbH) in a multi-trauma patient with pulmonary contusion and pre-existing cyanotic congenital heart disease and in a patient with raised intracranial pressure in the context of acute liver failure and primary graft non-function. In both cases, heart-lung interactions were complex, but AV-ECCO2R brought about significant improvements in respiratory indices and left/right ventricular function. The device facilitated restoration of homeostasis where other therapeutic options were limited or had failed.

Purpose The aim of the present study was to correlate computed tomography appearances with clinical severity and outcome using a total lung disease (TLD) score in patients with acute respiratory distress syndrome (ARDS) related to influenza A H1N1 infection. Materials and Methods Chest computed tomographic scans of 33 patients admitted in the intensive care unit with ARDS related to influenza A H1N1 were retrospectively reviewed. Total lung disease was calculated from the combined extent of consolidation (TLC) and ground glass (TLGG) in the anterior, middle, and posterior segments of the lungs at 3 different levels (apex, hila, and base) using the method described by Goodman et al ( Radiology . 213:545-552;1999). Total lung disease, TLC, and TLGG were statistically correlated with demographic characteristics, requirement for extracorporeal membrane oxygenation (ECMO) treatment, and patient outcome. Results Total lung disease is higher in patients who require ECMO treatment ( P = .016). It is significantly higher ( P = .003) in the posterior segments and significantly lower ( P = .0001) in the anterior segments compared with TLGG. Total consolidation significantly increases ( P = .0001), whereas TLGG significantly decreases ( P = .0001) from the anterior toward the posterior segments. There is also a significant increase in TLD ( P = .0001), TLC ( P = .0001), and TLGG ( P = .004) from the apices to the lung bases. There is a negative correlation between TLD and age ( P = .01), and TLGG and body mass index ( P = .014). Total consolidation is higher ( P = .013) and TLGG is lower ( P = .012) in patients with a body mass index greater than 30 kg/m 2 . Conclusion A greater extent of air-space disease in ARDS related to influenza A H1N1 infection is associated with progression to ECMO treatment and, therefore, clinical severity. The extent of total air-space disease is greater in younger patients, and obesity is related to a more extensive consolidation.

BACKGROUND Intensive insulin therapy (IIT) has been shown to reduce mortality and morbidity in longer stay, critically ill patients. However, this has been demonstrated in a single site, whereas two multicentric studies have been terminated prematurely mainly due to hypoglycemia. Other difficulties with IIT include efficacy of glycemic control. This report describes how IIT can be improved by protocol simplification and removal of glucose supplementation. METHODS A clinical information system established at each bedspace guided staff through the IIT algorithms. Time spent within predefined glycemic ranges was calculated assuming a linear trend between successive measurements. Three groups were investigated retrospectively: IIT1 protocol,(1) an updated IIT2 version, and intuitive nurse dosing of conventional insulin therapy (CIT). RESULTS Fifty consecutive, critically ill patients were included in each study group. Patient characteristics were similar in each group. The frequency of CIT and IIT2 blood glucose measurements were 11.6 and 11.5 measurements per day, respectively, while the IIT1 measurements were more frequent (14.5 measurements per day). The mean proportion of time spent in the target glycemic range (4.4-6.1 mmol/liter) was highest in the IIT2 group (34.9%), as compared to the IIT1 (22.9%) and CIT groups (20.3%) (p

Objective: Sepsis and its sequelae are the leading cause of death in critically ill patients. Discovery in the late 1990s of Toll-like receptors as primary sensors of microbial infection led to significant advances in understanding the pathogenesis of sepsis, including emerging differences between Gram-positive and Gram-negative infection and the potential for the manipulation of Toll-like receptors for the treatment of sepsis. This review describes these advances. Methods: Bibliographic search of the literature since 1999, with particular emphasis on the conceptual and therapeutic implications of Toll-like receptors for patients with systemic sepsis. Results and Conclusions: Toll-like receptors initiate the inflammatory processes that underlie the clinical response to infection and therefore represent an important putative target for therapeutic intervention.

Volume resuscitation is clinically beneficial in patients with sepsis, but few data exist concerning the effects of fluid administration on early events in the inflammatory process. Vascular permeability, leukocyte rolling and leukocyte adhesion in the rodent mesenteric microcirculation were assessed in vivo using intravital microscopy, and the effect of fluid administration on lipopolysaccharide (LPS)-induced changes recorded. Prospective, repeated measures study. University hospital laboratory. Male Wistar rats in six groups. All animals underwent intravital microscopic examination of mesenteric post-capillary venules. LPS or vehicle was applied topically. Animals received either no additional fluids, 0.9% saline (16 ml/kg per h) or 5% human albumin (16 ml/kg per h) commencing 30 min prior to LPS/vehicle administration. Leukocyte rolling, firm adhesion and blood velocity were observed directly. Vascular permeability was assessed using the flux of fluorescently labelled albumin into the interstitium. LPS significantly increased the median (IQR) number of leukocytes rolling and firmly adherent relative to baseline (at 60 min rolling increased from 12.0 (10.3–13.8) to 40.3 (36.0–47.5) cells/min; adhesion increased from 1 (1–2) to 17 (12–26) cells/100 μm; n=5, p

The acute respiratory distress syndrome occurs commonly in critical care. There is an increasing volume of clinical and experimental evidence that poor ventilatory technique that is injurious to the lungs can propagate the systemic inflammatory response and adversely affect mortality. Many ventilatory techniques have been hypothesized to 'protect' the lungs during mechanical ventilation, including tidal volume limitation, high positive end-expiratory pressure, pressure-controlled inverse ratio ventilation, and prone positioning. Experimental techniques include liquid ventilation, surfactant administration and extracorporeal gas exchange. Despite excellent rationale for their use, few techniques, apart from tidal volume limitation, have been shown to improve survival in randomized controlled trials.

Acute severe clinical deterioration of patients with cystic fibrosis (CF) may mandate endotracheal intubation. The benefits of intubation were evaluated by examining which pre-admission parameters were associated with intensive care unit (ICU) outcome and assessing the potential benefits of intubation for survivors in terms of time from ICU discharge to death.A retrospective analysis of data from a single centre was undertaken.Thirty patients required intubation on 34 occasions (8 per 1000 admissions). Eleven patients died in ICU and 7 after ICU but not hospital discharge. Fifty-nine per cent of 22 patients intubated for pneumothorax and/or haemoptysis survived to hospital discharge. Of the twelve intubated for infective exacerbations, 33% survived to hospital discharge. Those who died after hospital discharge survived 447 days. There were no significant differences for survivors in reasons for intubation, colonizing organism, frequency of infective exacerbations, severity of illness or pulmonary physiology. Osteoporosis and a greater fall in body mass index over the 24 months prior were more frequent in non-survivors.Patients with CF developing haemoptysis and/or pneumothorax should be admitted to ICU and intubated promptly, should this be required. Chronic disease markers may be more relevant prognostically than rates of hospitalization or forced expiratory volume in 1 s decline which should not be bars to invasive ventilation.

Optimal management of the acute respiratory distress syndrome (ARDS) requires prompt recognition, treatment of the underlying cause and the prevention of secondary injury. Ventilator-associated lung injury (VALI) is one of the several iatrogenic factors that can exacerbate lung injury and ARDS. Reduction of VALI by protective low tidal volume ventilation is one of the only interventions with a proven survival benefit in ARDS. There are, however, several factors inhibiting the widespread use of this technique in patients with established lung injury. Prevention of ARDS and VALI by detecting at-risk patients and implementing protective ventilation early is a feasible strategy. Detection of injurious ventilation itself is possible, and potential biological markers of VALI have been investigated. Finally, facilitation of protective ventilation, including techniques such as extracorporeal support, can mitigate VALI.

Introduction and objectives Patients with pulmonary hypertension (PH) represent an extremely high-risk surgical group, with previous reported mortality 7–18%, and predicting perioperative risk is difficult. The aim of this study was to characterise a current cohort of patients with pulmonary hypertension undergoing surgery in a National UK Designated PH centre and to determine predictors of adverse events. Methods Consecutive patients with PH undergoing non-cardiac, non-obstetric surgery were identified by matching theatre and PH databases between 1st April 2008 and 1st April 2015. Demographics, recent echocardiogram, right heart catheterisation, B-natriuretic peptide (BNP), six-minute walk test (6MWT) and World Health Organisation functional class (WHO-FC) on last clinic visit was recorded. Anaesthetic and perioperative details; post-operative management, short-term morbidity and 28-day outcome were recorded. Data are mean±SD or median (range). Results 37 procedures requiring anaesthesia were identified in 32 patients with PAH (7 idiopathic PAH, 1 PVOD, 24 CHD-PAH, 4 CTD-PAH) and 1 CTEPH. Average age was 44.4 ± 13 years, 27(84%) were female. Baseline preoperative WHO-FC was II (3, 9%), III (28, 88%), IV (1, 3%). Baseline 6MWT distance was 317 ± 68 m; BNP 200 (12–2027) ng/L; RV systolic pressure (RVSP) 85 ± 16 mmHg, tricuspid annular planar systolic excursion (TAPSE) 18 ± 7 mm. Cases including oesophagogastroscopy (n = 4), dental extraction (n = 8) under general anaesthesia (GA) were classified as minor; 6 (16%) including mastectomy, laparotomy and fasciotomy as major surgical procedures. Almost all (95%) were performed under GA; most were elective procedures and were monitored on the high dependency or intensive care unit post-operatively. Cardiovascular perioperative complications occurred in 6 cases (16%) including death in 2 patients (5.4%) in the days following surgery, in both cases related to PH crises, resulting in right ventricular (RV) failure. Baseline parameters of RV function including RVSP, TAPSE and the presence of a pericardial effusion were associated with adverse events. Conclusion Perioperative mortality in patients with PH remains high, even in the current era. If surgery is deemed essential, PH centres with experts in cardiothoracic anaesthesia and ICU should be involved in preoperative planning with the PH multidisciplinary team guiding appropriate selection of patients, considering pulmonary haemodynamics and indices of RV function, as well as surgical factors.

The case histories are presented of three adults who had severe hypercapnic acidosis despite mechanical ventilation with what were considered to be injurious tidal volumes and airway pressures. The use of a percutaneously inserted arteriovenous extracorporeal carbon dioxide removal (AV-ECCO(2)R) device facilitated a dramatic reduction in the amount of ventilatory support required, achieving a "lung-protective" level. Two patients survived to hospital discharge. One patient died after it became apparent that her late-stage interstitial lung disease was unresponsive to immunosuppression. AV-ECCO(2)R may be a useful strategy in facilitating lung-protective ventilation.

Carbon dioxide is excreted by the lungs. Carbon dioxide production is based on metabolic rate and the substrates that are being utilized to drive the Kreb's cycle. Factors that influence pulmonary elimination of carbon dioxide include the volume of dead space, tidal volume, respiratory frequency and positive end-expiratory pressure (PEEP). The balance between arterial and venous carbon dioxide is based upon cardiac output. Hypocapnia can be controlled relatively through adjustment of ventilator settings to reduce minute ventilation in the sedated patient. The effects of hypercapnia and the associated acidaemia may be mitigated through the use of buffering agents. Traditionally, extracorporeal gas exchange (ECGE) has been utilized in patients only as a rescue therapy. In practice, clinicians adopt a technique somewhere between optimal carbon dioxide clearance and more liberal clearance targets, based on assessment of the severity of lung disease and the risks and benefits of ventilatory manipulations or associated interventions.

The systemic inflammatory response syndrome (SIRS) is the leading cause of morbidity & mortality in the critically ill. It is associated with a 50% reduction in 5 year life expectancy. SIRS is defined as 2 of the following criteria: heart rate >90, respiratory rate >20 or pCO 2 38°C, white cell count 12 x10 9 /l. These criteria are used to stratify patients for specific therapies & in research to define interventional groups. Cardiac surgery is associated with systemic inflammation. The validity of the SIRS criteria have never been formally evaluated post cardiac surgery. We undertook to describe the incidence of SIRS post cardiac surgery & relate this to outcome. Methods: We retrospectively analysed prospectively collected data from 2764 consecutive admissions following cardiac surgery (coronary bypass grafting 1425, valve surgery 763, combined procedure 252, other 324). The number of criteria met simultaneously within 1 hour epochs was recorded for the entire admissions. Results: 96.4%, 57.9% & 12.2% of patients met at least 2, 3 or 4 criteria respectively within 24hrs of admission. The temperature criterion was least often fulfilled. ICU mortality was 2.67%. Length of stay exceeded 3 days in 18.5% of patients. The capacity of the criteria to predict mortality & prolonged ICU stay is presented in the table . Discussion: Nearly all patients fulfilled the standard 2 criteria definition of SIRS within 24hrs of admission. This definition does not adequately define the subgroup of patients with greater systemic inflammation, mortality or length of stay. Thus, some clinical manifestations of inflammation are very common following cardiac surgery, although not necessarily prognostic. By contrast, the presence of 3 or more criteria was more discriminatory of death & prolonged ICU stay. We propose that 3 or more SIRS criteria is a more appropriate threshold that defines those patients with clinically significant inflammation post cardiac surgery.

Lipoteichoic acid (LTA), an immunostimulatory component of the cell walls of gram positive bacteria, has pro-inflammatory effects in vitro and in vivo. However, one in vivo study concluded that LTA had no noticeable effects on leukocyte recruitment. In this study we investigated the effects of highly purified LTA, prepared by butanol extraction (Bu-LTA) at room temperature, on in vivo leukocyte adhesion. Using intravital microscopy we measured adhesion of leukocytes in mesenteric post-capillary venules of rats and mice. Topical superfusion of Bu-LTA (1 microg/ml) in rats significantly (p0.05) increased adhesion within 30 min. By contrast, hot phenol-extracted LTA did not increase adhesion. Alkaline hydrolysis of Bu-LTA removed alanine residues and prevented adhesion. Also, pre-administration of anti-rat beta2-integrin antibody abolished Bu-LTA-induced adhesion. Finally, intraperitoneal injection of Bu-LTA (100 microg/ml) into mice also significantly (p0.01) increased leukocyte adhesion measured at 60 min. In conclusion, Bu-LTA with intact alanine residues promotes beta2-integrin-dependent leukocyte adhesion in vivo.

Objective: Arterial carboxyhemoglobin is elevated in patients with critical illness. It is an indicator of the endogenous production of carbon monoxide by the enzyme heme oxygenase, which modulates the response to oxidant stress. The objective was to explore the hypothesis that arterial carboxyhemoglobin level is associated with inflammation and survival in patients requiring cardiothoracic intensive care. Design: Prospective, observational study. Setting: A cardiothoracic intensive care unit. Patients: All patients admitted over a 15-month period. Interventions: None. Measurements and Main Results: Arterial carboxyhemoglobin, bilirubin, and standard biochemical, hematologic, and physiologic markers of inflammation were measured in 1,267 patients. Associations were sought between levels of arterial carboxyhemoglobin, markers of the inflammatory response, and clinical outcome. Intensive care unit mortality was associated with lower minimum and greater maximal carboxyhemoglobin levels (p

Use of inhaled nitric oxide for treatment of pulmonary hypertension in adult critical illness is limited by its mode of delivery and high costs, prompting evaluation of alternative therapies. We report the use of oral sildenafil in a patient with severe secondary pulmonary hypertension and right ventricular dysfunction. Following reduction in mean pulmonary artery pressure and pulmonary vascular resistance with inhaled nitric oxide, crossover to sildenafil therapy maintained control of pulmonary hypertension, facilitating discontinuation of respiratory and cardiovascular organ support. The relative pulmonary vascular specificity of oral sildenafil, and its low cost, makes it an attractive therapeutic alternative to inhaled nitric oxide, and warrants further study.

Lethal necrotizing fasciitis caused by Streptococcus pyogenes is characterized by a paucity of neutrophils at the site of infection. Interleukin (IL)-8, which is important for neutrophil transmigration and activation, can be degraded by S. pyogenes. Blood isolates of S. pyogenes were better able to degrade human IL-8 than throat isolates. Degradation of IL-8 was the result of a single specific cleavage between 59glutamine and 60arginine within the IL-8 C-terminal alpha helix. Cleaved IL-8 reduced neutrophil activation and migration. IL-8-cleaving activity was found in partially purified supernatant of a necrotizing fasciitis isolate, and this activity was associated with an approximately 150-kDa fraction containing S. pyogenes cell envelope proteinase (SpyCEP). IL-8-cleaving activity corresponded with the presence of SpyCEP in the supernatant. Cleavage of IL-8 by S. pyogenes represents an unprecedented mechanism of immune evasion, effectively preventing IL-8 C-terminus-mediated endothelial translocation and subsequent recruitment of neutrophils.