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Burns inhalation injury increases the attributable mortality of burns related trauma. However, diagnostic uncertainties around bronchoscopically graded severity, and its effect on outcomes, remain. This study evaluated the impact of different bronchoscopic burns inhalation injury grades on outcomes.A single-centre cohort study of all patients admitted to the London Burns centre intensive care unit (BICU) over 12 years. Demographic data, burn and burns inhalation injury characteristics, and ICU-related parameters were collected retrospectively. The primary outcome was mortality. Secondary outcomes were hospital and ICU lengths of stay. The impact of pneumonia was determined. Univariate and multivariable Cox's proportional hazards regression analyses informed factors predicting mortality.Burns inhalation injury was diagnosed in 84 of 231 (36%) critically ill burns patients; 20 mild (grade 1), 41 severe (grades 2/3) and 23 unclassified bronchoscopically. Median (IQR) total body surface area burned (TBSA) was 20% (10-40). Mortality was significantly higher in patients with burns inhalation injury vs those without burns inhalation injury (38/84 [45%] vs 35/147 [24%], p 0.001). Patients with pneumonia had a higher mortality than those without (34/125 [27%] vs 8/71 [11%], p = 0.009). In multivariable analysis, severe burns inhalation injury significantly increased mortality (adjusted HR=2.14, 95%CI: 1.12-4.09, p = 0.022), compared with mild injury (adjusted HR=0.58, 95% CI: 0.18-1.86, p = 0.363). Facial burns (adjusted HR=3.13, 95%CI: 1.69-5.79, p 0.001), higher TBSA (adjusted HR=1.05, 95%CI: 1.04-1.06, p 0.001) and older age (adjusted HR=1.04, 95%CI: 1.02-1.07, p 0.001) also independently predicted mortality, though pneumonia did not.Severe burns inhalation injury is a significant risk factor for mortality in critically ill burns patients. However, pneumonia did not increase mortality from burns inhalation injury. This work confirms prior implications of bronchoscopically graded burns inhalation injury. Further study is suggested, through registries, into the diagnostic accuracy and reliability of bronchoscopy in burns related lung injury.

AIMS: Comprehensive echocardiography assessment of right ventricular (RV) impairment has not been reported in critically ill patients with COVID-19. We detail the specific phenotype and clinical associations of RV impairment in COVID-19 acute respiratory distress syndrome (ARDS). METHODS: Transthoracic echocardiography (TTE) measures of RV function were collected in critically unwell patients for associations with clinical, ventilatory and laboratory data. RESULTS: Ninety patients (25.6% female), mean age 52.0 ± 10.8 years, veno-venous extracorporeal membrane oxygenation (VVECMO) (42.2%) were studied. A significantly higher proportion of patients were identified as having RV dysfunction by RV fractional area change (FAC) (72.0%,95% confidence interval (CI) 61.0-81.0) and RV velocity time integral (VTI) (86.4%, 95 CI 77.3-93.2) than by tricuspid annular plane systolic excursion (TAPSE) (23.8%, 95 CI 16.0-33.9), RVS' (11.9%, 95% CI 6.6-20.5) or RV free wall strain (FWS) (35.3%, 95% CI 23.6-49.0). RV VTI correlated strongly with RV FAC (p ≤ 0.01). Multivariate regression demonstrated independent associations of RV FAC with NTpro-BNP and PVR. RV-PA coupling correlated with PVR (univariate p

OBJECTIVES: Severe coronavirus disease 2019 is associated with an extensive pneumonitis and frequent coagulopathy. We sought the true prevalence of thrombotic complications in critically ill patients with severe coronavirus disease 2019 on the ICU, with or without extracorporeal membrane oxygenation. DESIGN: We undertook a single-center, retrospective analysis of 72 critically ill patients with coronavirus disease 2019-associated acute respiratory distress syndrome admitted to ICU. CT angiography of the thorax, abdomen, and pelvis were performed at admission as per routine institution protocols, with further imaging as clinically indicated. The prevalence of thrombotic complications and the relationship with coagulation parameters, other biomarkers, and survival were evaluated. SETTING: Coronavirus disease 2019 ICUs at a specialist cardiorespiratory center. PATIENTS: Seventy-two consecutive patients with coronavirus disease 2019 admitted to ICU during the study period (March 19, 2020, to June 23, 2020). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All but one patient received thromboprophylaxis or therapeutic anticoagulation. Among 72 patients (male:female = 74%; mean age: 52 ± 10; 35 on extracorporeal membrane oxygenation), there were 54 thrombotic complications in 42 patients (58%), comprising 34 pulmonary arterial (47%), 15 peripheral venous (21%), and five (7%) systemic arterial thromboses/end-organ embolic complications. In those with pulmonary arterial thromboses, 93% were identified incidentally on first screening CT with only 7% suspected clinically. Biomarkers of coagulation (e.g., D-dimer, fibrinogen level, and activated partial thromboplastin time) or inflammation (WBC count, C-reactive protein) did not discriminate between patients with or without thrombotic complications. Fifty-one patients (76%) survived to discharge; 17 (24%) patients died. Mortality was significantly greater in patients with detectable thrombus (33% vs 10%; p = 0.022). CONCLUSIONS: There is a high prevalence of thrombotic complications, mainly pulmonary, among coronavirus disease 2019 patients admitted to ICU, despite anticoagulation. Detection of thrombus was usually incidental, not predicted by coagulation or inflammatory biomarkers, and associated with increased risk of death. Systematic CT imaging at admission should be considered in all coronavirus disease 2019 patients requiring ICU.

Rationale: Clinical and epidemiologic data in coronavirus disease (COVID-19) have accrued rapidly since the outbreak, but few address the underlying pathophysiology. Objectives: To ascertain the physiologic, hematologic, and imaging basis of lung injury in severe COVID-19 pneumonia. Methods: Clinical, physiologic, and laboratory data were collated. Radiologic (computed tomography (CT) pulmonary angiography [n = 39] and dual-energy CT [DECT, n = 20]) studies were evaluated: observers quantified CT patterns (including the extent of abnormal lung and the presence and extent of dilated peripheral vessels) and perfusion defects on DECT. Coagulation status was assessed using thromboelastography. Measurements and Results: In 39 consecutive patients (male:female, 32:7; mean age, 53 ± 10 yr [range, 29–79 yr]; Black and minority ethnic, n = 25 [64%]), there was a significant vascular perfusion abnormality and increased physiologic dead space (dynamic compliance, 33.7 ± 14.7 ml/cm H2O; Murray lung injury score, 3.14 ± 0.53; mean ventilatory ratios, 2.6 ± 0.8) with evidence of hypercoagulability and fibrinolytic “shutdown”. The mean CT extent (±SD) of normally aerated lung, ground-glass opacification, and dense parenchymal opacification were 23.5 ± 16.7%, 36.3 ± 24.7%, and 42.7 ± 27.1%, respectively. Dilated peripheral vessels were present in 21/33 (63.6%) patients with at least two assessable lobes (including 10/21 [47.6%] with no evidence of acute pulmonary emboli). Perfusion defects on DECT (assessable in 18/20 [90%]) were present in all patients (wedge-shaped, n = 3; mottled, n = 9; mixed pattern, n = 6). Conclusions: Physiologic, hematologic, and imaging data show not only the presence of a hypercoagulable phenotype in severe COVID-19 pneumonia but also markedly impaired pulmonary perfusion likely caused by pulmonary angiopathy and thrombosis.

Background UK data suggest 6% of COVID-19 hospital admissions are either currently pregnant or immediately post-partum. However, the current literature suggests that if COVID-19 occurs in pregnancy, or post-partum, symptoms are mostly mild. Methods All COVID-19 admissions to one acute London National Health Service Foundation trust were reviewed since the beginning of the COVID-19 pandemic to 1 May 2020 to establish whether there were any pregnant or immediately post-partum admissions. Data were extracted from hospital electronic records and anonymised. Any patients admitted to adult intensive care unit had their case notes reviewed in detail and comparison made to a local risk-assessment guideline identifying patients at-risk of thromboembolic events or cytokine storms. Local hospital guidelines were followed. Patients admitted to adult intensive care unit gave written consent. Results A total of 24 pregnant or immediately post-partum patients with COVID-19 were admitted. Three patients required long adult intensive care unit admissions for severe single-organ respiratory failure after emergency C-sections. Two of these patients required proning (three times and eight times, respectively). All were considered medium risk for thromboembolic events but had rising D-dimers following adult intensive care unit admission, resulting in increased dosing of pharmacological thromboprophylaxis throughout their admission. All were considered low risk for a cytokine storm, and none had any significant cardiovascular or renal involvement. One patient developed a super-imposed fungal lung infection. All three patients developed delirium following cessation of sedation. Conclusion Pregnant or immediately post-partum women can develop severe COVID-19 symptoms requiring prolonged adult intensive care unit admission. It is likely to be single-organ failure, but patients are at a high risk of a thromboembolic event and delirium.

The year 2016 marks the 200th anniversary of Laennec's invention of the stethoscope, with the subsequent publication of auscultatory sounds for clinical diagnosis in 1819. Today, history and examination remain pivotal to accurate diagnosis. The hypotheticodeductive method of diagnosis based on Bayes' theorem requires a detailed history and examination skills to elicit symptoms and signs. The key symptoms of respiratory disease are breathlessness, chest pain, wheeze, cough and associated sputum production. Non-respiratory conditions may also produce such symptoms. A systematic approach to history-taking should include all primary symptoms, their time-course, characteristics, severity and trajectory. A review of non-respiratory associations, pharmaceutical and historical aspects of respiratory symptoms should precede a thorough review of clinical signs. Further questioning or examination will lead to assimilation of information, synthesis with clinicopathophysiological knowledge of respiratory diseases, and formulation of a differential diagnosis. On examination, based on the model of inspection, palpation, percussion and auscultation, there are a few classical patterns of the most important focal abnormalities, although there may be an absence of clinical signs. This article reviews the key features of respiratory symptoms and signs, outlines tips on how best to elicit these, and discusses patterns of clinical features suggesting certain diagnoses.

PurposeTo describe the incidence of pulmonary artery thrombosis in COVID-19 versus influenza pneumonia using CT angiography and to assess whether it may increase the risk of pulmonary hypertension.Materials and MethodsSingle and dual energy CT pulmonary angiography of age- and gender-matched patients with influenza and COVID-19 pneumonia, referred for extra-corporeal membrane oxygenation (ECMO) and/or mechanical ventilation from January 2016 to January 2021, were retrospectively evaluated. Two independent observers qualitatively and quantitively assessed clot burden and Qanadli CT Obstruction Index. Two consensus observers calculated pulmonary artery volume and right to left ventricular diameter ratio (Terarecon, California, USA) to diagnose pulmonary hypertension. Pulmonary infarct volume and perfused blood volume relative enhancement were also calculated (Syngo via, Siemens Healthineers, Forchheim, Germany). All radiologic parameters were correlated with clinical data. To assess if in situ thrombosis could be visualised on CT, isolated segmental and subsegmental filling defects were used as an imaging surrogate. For statistical analyses, Graphpad Prism9 and IBM SPSS v27.0 software were used.ResultsThe incidence of either central PE or DVT was equal between patients with COVID-19 and influenza pneumonia (20%). The incidence of isolated segmental and subsegmental filling defects was higher in COVID-19 but without statistical significance (44% vs 32%;p=0.5607). Right to left ventricular diameter and pulmonary artery to aorta ratios were higher in COVID-19 compared to influenza (1.01 vs 0.866 and 1.04 vs 0.904;p=0.0071 and p=0.0023, respectively).ConclusionIn a comparable group of patients with severe COVID-19 and influenza pneumonia, CT features of pulmonary hypertension are more often present in patients with COVID-19 pneumonia despite an equal clot burden on CT. This is not attributable to pulmonary thrombosis visible on CT and supports the hypothesis that micro- rather than macrovascular obstruction is the cause of severe hypoxia in COVID-19 pneumonia.

A significant proportion of patients with COVID-19 develop acute respiratory distress syndrome (ARDS) with high risk of death. The efficacy of veno-venous extracorporeal membrane oxygenation (VV-ECMO) for COVID-19 on longer-term outcomes, unlike in other viral pneumonias, is unknown. In this study, we aimed to compare the 6 month mortality of patients receiving VV-ECMO support for COVID-19 with a historical viral ARDS cohort. Fifty-three consecutive patients with COVID-19 ARDS admitted for VV-ECMO to the Royal Brompton Hospital between March 17, 2020 and May 30, 2020 were identified. Mortality, patient characteristics, complications, and ECMO parameters were then compared to a historical cohort of patients with non-COVID-19 viral pneumonia. At 6 months survival was significantly higher in the COVID-19 than in the non-COVID-19 viral pneumonia cohort (84.9% vs. 66.0%, p = 0.040). Patients with COVID-19 had an increased Murray score (3.50 vs. 3.25, p = 0.005), a decreased burden of organ dysfunction (sequential organ failure score score [8.76 vs. 10.42, p = 0.004]), an increased incidence of pulmonary embolism (69.8% vs. 24.5%, p < 0.001) and in those who survived to decannulation longer ECMO runs (19 vs. 11 days, p = 0.001). Our results suggest that survival in patients supported with EMCO for COVID-19 are at least as good as those treated for non-COVID-19 viral ARDS.

Background Rapid molecular diagnostic tests to investigate the microbial aetiology of pneumonias may improve treatment and antimicrobial stewardship in intensive care units (ICUs). Clinicians’ endorsement and uptake of these tests is crucial to maximise engagement; however, adoption may be impeded if users harbour unaddressed concerns or if device usage is incompatible with local practice. Accordingly, we strove to identify ICU clinicians’ beliefs about molecular diagnostic tests for pneumonias before implementation at the point-of-care. Methods We conducted semi-structured interviews with 35 critical care doctors working in four ICUs in the United Kingdom. A clinical vignette depicting a fictitious patient with signs of pneumonia was used to explore clinicians’ beliefs about the importance of molecular diagnostics and their concerns. Data were analysed thematically. Results Clinicians’ beliefs about molecular tests could be grouped into two categories: perceived potential of molecular diagnostics to improve antibiotic prescribing (Molecular Diagnostic Necessity) and concerns about how the test results could be implemented into practice (Molecular Diagnostic Concerns). Molecular Diagnostic Necessity stemmed from beliefs that positive results would facilitate targeted antimicrobial therapy; that negative results would signal the absence of a pathogen, and consequently that having the molecular diagnostic results would bolster clinicians’ prescribing confidence. Molecular Diagnostic Concerns included unfamiliarity with the device’s capabilities, worry that it would detect non-pathogenic bacteria, uncertainty whether it would fail to detect pathogens, and discomfort with withholding antibiotics until receiving molecular test results. Conclusions Clinicians believed rapid molecular diagnostics for pneumonias were potentially important and were open to using them; however, they harboured concerns about the tests’ capabilities and integration into clinical practice. Implementation strategies should bolster users’ necessity beliefs while reducing their concerns; this can be accomplished by publicising the tests’ purpose and benefits, identifying and addressing clinicians’ misconceptions, establishing a trial period for first-hand familiarisation, and emphasising that, with a swift (e.g., 60–90 min) test, antibiotics can be started and refined after molecular diagnostic results become available.

Rationale Upper limb dysfunction is well recognised in survivors of intensive care (Gustafson et al Crit Care Med 2018;46:1769-1774). A mainstay of respiratory support through the COVID-19 pandemic has been use of repeated patient prone positioning to improve ventilation. Potential complications reported with prone positioning of sedated patients include brachial plexopathy, shoulder subluxation and peripheral nerve injury. We hypothesised that there would be a high prevalence of upper limb dysfunction, disability and pain in survivors of COVID-19 requiring mechanical ventilation, particularly in those who were prone positioned. Methods Eligible patients were laboratory-confirmed swab positive for SARS-CoV-2, mechanically ventilated for a minimum of 72 hours on the Royal Brompton Hospital Adult Intensive Care Units. We measured handgrip strength (HGS), normalised for age and sex, the Disability of Arm Shoulder Hand (DASH) questionnaire (Beaton et al J Hand Ther 2001;14:128-146) and Upper limb Pain Numerical Rating Scale (from 0-10). Health related quality of life was measured using the EuroQol-5 dimensions 5-level (EQ5D5L Utility Index (UI) and Visual Analogue Score (VAS)). Patients were stratified according to whether they received prone positioning or not. Results Twenty-seven consecutive patients were assessed at mean 45 days after hospital discharge. Baseline demographics, admission characteristics, and follow-up upper limb assessment data are shown in Table 1. There was evidence of upper limb weakness (mean (SD) right HGS: 44.77(19.31) %predicted;left HGS 47.69 (18.41) %predicted), with 63% showing upper limb dysfunction (DASH ≥ 16) and 33% showing severe upper limb dysfunction (DASH ≥40). Median (IQR) pain scores were 4 (0.75-6.25) with 53% reporting severe pain (≥ 5). DASH correlated significantly with EQ5D5L UI and VAS (r=-0.69 and r=-0.73 respectively;both p

Background Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. Methods Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p Results Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16–24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. Conclusion Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. Trial registration: The study was registered with Clinical trials.gov Identifier: NCT04534569.

Introduction COVID-19 mortality rates are high, particularly in patients requiring invasive ventilatory support, developing a cytokine storm, or experiencing thromboembolic disease Our goal was to determine if traffic-light driven, personalised care was associated with improved survival in acute hospital settings Methods Outcomes were evaluated during two implementation phases of a real-time clinical decision support tool that had been developed as part of a Trust's COVID-19 response, using a reporting and bioinformatics team to support Clinical and Operational teams Following optimisation, the tool defined patients' clinical status in terms of risk of preventable complications based on blood test results (Ddimer, C reactive protein and ferritin) Feedback to wardbased clinicians enabled rapid modification of care pathways, in the first phase following a daily review, and in the second phase, in real-time (dashboard updated every 10 minutes) Results 1039 COVID-19 positive patients were admitted by 21/05/2020 Focusing on the first 939 completed encounters to death or home discharge (median age 69ys;60% [563/939] male), 568/939 (60 4%) received thromboembolism risk flags, and 212/939 (22 5%) cytokine storm flags The maximum thromboembolism flag discriminated completed encounter mortality between no flag (9 97% [37/371]);medium-risk (28 5% [68/239]);high-risk (51 2% [105/205]);and suspected thromboembolism (52 4% [65/124]), Kruskal Wallis p

Background Corona Virus Disease 2019 (COVID-19) pneumonitis associated with severe respiratory failure carries a high mortality. Coagulopathy has emerged as a significant contributor to thrombotic complications. Case summary We describe two cases of severe COVID-19 pneumonitis refractory to conventional mechanical ventilation and proning position, transferred to our specialist centre for cardiorespiratory failure. Cross-sectional imaging demonstrated concurrent venous and aortic thrombosis with end-organ ischaemic changes. One patient received thrombolysis with a partial response. This could not be offered to the other patient due to a recent haemorrhagic event. Both patients died of multi-organ failure in the hospital. Discussion Concurrent aortic and venous thromboses are rare. This finding in COVID-19 cases, who were both critically ill patients, likely reflects the strongly thrombogenic nature of this illness which ultimately contributed to poor outcomes. The absence of deep vein thrombosis or a potential systemic source of embolism suggests in situ thrombosis. Further, the management of anticoagulation and thrombolysis is challenging in patients where an attendant bleeding risk exists.

Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) provides a bridge to recovery in patients with acute respiratory failure due to the acute respiratory distress syndrome (ARDS). Survival in ARDS has improved over 15 years, and VV-ECMO may rescue even the most severe of these patients. Predictors of survival on ICU are based upon the principles of reversibility of the inciting aetiology, and premorbid 'reserve' - an imprecise term encompassing comorbidities and frailty. ECMO can support failing organs for prolonged periods, thus sometimes masking trajectories of decline, or unmasking irretrievable intrinsic conditions at a later time point in the critical illness. Clinicians are confronted with new on-treatment dilemmas: how long should we continue this high level of care? Will the patient's limited respiratory reserve manage off ECMO? Or are we hastening their demise? How long is it justifiable to keep someone on ECMO, if the predicted survival off is ultimately poor, but they are in a stable state whilst supported? The palliative withdrawal from ECMO is unchartered territory that requires further study. We describe two representative cases and discuss the wide ethical issues surrounding the initiation and withdrawal of ECMO. ispartof: ACTA CARDIOLOGICA vol:76 issue:5 pages:455-458 ispartof: location:England status: published

Common causes of death in COVID-19 due to SARS-CoV-2 include thromboembolic disease, cytokine storm and adult respiratory distress syndrome (ARDS). Our aim was to develop a system for early detection of disease pattern in the emergency department (ED) that would enhance opportunities for personalised accelerated care to prevent disease progression. A single Trust’s COVID-19 response control command was established, and a reporting team with bioinformaticians was deployed to develop a real-time traffic light system to support clinical and operational teams. An attempt was made to identify predictive elements for thromboembolism, cytokine storm and ARDS based on physiological measurements and blood tests, and to communicate to clinicians managing the patient, initially via single consultants. The input variables were age, sex, and first recorded blood pressure, respiratory rate, temperature, heart rate, indices of oxygenation and C-reactive protein. Early admissions were used to refine the predictors used in the traffic lights. Of 923 consecutive patients who tested COVID-19 positive, 592 (64%) flagged at risk for thromboembolism, 241/923 (26%) for cytokine storm and 361/923 (39%) for ARDS. Thromboembolism and cytokine storm flags were met in the ED for 342 (37.1%) patients. Of the 318 (34.5%) patients receiving thromboembolism flags, 49 (5.3% of all patients) were for suspected thromboembolism, 103 (11.1%) were high-risk and 166 (18.0%) were medium-risk. Of the 89 (9.6%) who received a cytokine storm flag from the ED, 18 (2.0% of all patients) were for suspected cytokine storm, 13 (1.4%) were high-risk and 58 (6.3%) were medium-risk. Males were more likely to receive a specific traffic light flag. In conclusion, ED predictors were used to identify high proportions of COVID-19 admissions at risk of clinical deterioration due to severity of disease, enabling accelerated care targeted to those more likely to benefit. Larger prospective studies are encouraged.

Studies conducted in people living with HIV (PLHIV) report high rates of sleep disturbance, without a clear explanation as to cause or effect. Therefore, we proposed use of multiple validated questionnaires that would allow a more comprehensive evaluation of sleep quality in PLHIV. We administered eight validated sleep and wellbeing questionnaires, recording different aspects of sleep in order to provide a comprehensive description of sleep quality, quantity, daytime functioning, wakefulness, and general wellbeing. Associations with demographics and clinical data were analyzed by univariable/multivariable analyses. Of 254 subjects 99% were male (98% men who have sex with men), 88% white, mean age 41 (SD ± 9.9) years, HIV duration eight years (SD ± 6.3), 94% were on antiretroviral therapy, mean CD4 cell count was 724 cells/mm3, 81% had HIV RNA

IntroductionSeveral viral respiratory infections - notably influenza - are associated with secondary bacterial infection and additional pathology. The extent to which this applies for COVID-19 is unknown. Accordingly, we aimed to define the bacteria causing secondary pneumonias in COVID-19 ICU patients using the FilmArray Pneumonia Panel, and to determine this test’s potential in COVID-19 management.MethodsCOVID-19 ICU patients with clinically-suspected secondary infection at 5 UK hospitals were tested with the FilmArray at point of care. We collected patient demographic data and compared FilmArray results with routine culture.ResultsWe report results of 110 FilmArray tests on 94 patients (16 had 2 tests): 69 patients (73%) were male, the median age was 59 yrs; 92 were ventilated. Median hospital stay before testing was 14 days (range 1-38). Fifty-nine (54%) tests were positive, with 141 bacteria detected. Most were Enterobacterales (n=55, includingKlebsiellaspp. [n= 35]) orStaphylococcus aureus(n=13), as is typical of hospital and ventilator pneumonia. Community pathogens, includingHaemophilus influenzae(n=8) andStreptococcus pneumoniae(n=1), were rarer. FilmArray detected one additional virus (Rhinovirus/Enterovirus) and no atypical bacteria. Fewer samples (28 % vs. 54%) were positive by routine culture, and fewer species were reported per sample;Klebsiellaspecies remained the most prevalent pathogens.ConclusionFilmArray had a higher diagnostic yield than culture for ICU COVID-19 patients with suspected secondary pneumonias. The bacteria found mostly were Enterobacterales,S. aureusandP. aeruginosa, as in typical HAP/VAP, but withKlebsiellaspp. more prominent. We found almost no viral co-infection. Turnaround from sample to results is around 1h 15 min compared with the usual 72h for culture, giving prescribers earlier data to inform antimicrobial decisions.

Objective To determine whether the trajectories of survivors and non-survivors are different in patients admitted to intensive care in London. Design In this case series of 15 survivors and 16 non-survivors, data from admission to discharge was collected and aligned to lowest PaO2/FiO2 ratio where aggregation and trends were demonstrated. Setting Single centre case-series in London, Intensive Care. Participants All non-survivors were included (n=16). A biased set of survivors (n=15) who were demonstrated an unexpected and rapid recovery after a prolonged period of mechanical ventilatory support. Results Respiratory failure trajectories of survivors and non-survivors were similar once aligned indicating, from a respiratory function perspective, it is difficult to identify survivors from non-survivors with some survivors improving late in their disease (day 20 - 30 from symptom onset) Non-survivors are admitted earlier in their disease (p < 0.05) and had worse organ failure requirements prior to the nadir of their respiratory funciton (p < 0.05) compard to survivors. Conclusion Analysis of multiple factors fails to differentiate between survivors and non-survivors. Even when faced with multiorgan failure, perseverance until discharge must be advocated as late improvements do occur in survivors.

BackgroundCOVID-19 is a global health emergency. Recent data indicate a 50% mortality rate across UK intensive care units.MethodsA single institution, two-centre retrospective analysis following implementation of a Decision Support tool and real-time data dashboard for early detection of patients requiring personalised enhanced care, focussing on respiratory rate, diastolic blood pressure, oxygenation indices, C-reactive protein, D-dimer and ferritin. Protocols differing from conventional practice included high-dose prophylactic anticoagulation for all COVID-19 positive patients and prescription of antioxidants.ResultsBy 22/04/2020, 923 patients tested COVID-19 positive. 569 patients (61.7%) were male. The majority presented with advanced disease: interquartile ranges were C-reactive protein 44.9-179mg/L, D-dimer 1070-3802ng/mL, and ferritin 261-1208µg/L. Completed case fatality rates were 25.1% [95% CI 20.0, 30.0] in females, 40.5% [95% CI 35.9, 45.0] in males. 139 patients were admitted to intensive care where current death rates are 16.2% [95% CI 3.8, 28.7] in females, 38.2% [95% CI 28.6, 47.8] in males with no trends for differences based on ethnicity. A real-time traffic lights dashboard enabled rapid assessment of patients using critical parameters to accelerate adjustments to management protocols. In total 513 (55.6%) of patients were flagged as high risk for thromboembolic disease, exceeding the numbers flagged for respiratory deteriorations (N=391, 42.4%), or cytokine storm (N=68, 7.4%). There was minimal evidence that age was associated with disease severity, but males had higher levels of all dashboard indices, particularly C-reactive protein and ferritin (pConclusionsSurvival rates are encouraging. Protocols employed (traffic light-driven personalised care, protocolised early therapeutic anticoagulation based on D-dimer >1,000ng/mL and/or CRP>200 mg/L, personalised ventilatory strategies and antioxidants) are recommended to other units. Males are at greater risk of severe disease, most likely as the obligate SARS-CoV-2 receptor is encoded by the X-chromosome, and require especially close, and early attention.

The severe acute respiratory syndrome coronavirus 2 pandemic is to date affecting more than a million of patients and is challenging healthcare professionals around the world. Coronavirus disease 2019 may present with a wide range of clinical spectrum and severity, including severe interstitial pneumonia with high prevalence of hypoxic respiratory failure requiring intensive care admission. There has been increasing sharing experience regarding the patient's clinical features over the last weeks which has underlined the need for general guidance on treatment strategies. We summarise the evidence existing in the literature of oxygen and positive pressure treatments in patients at different stages of respiratory failure and over the course of the disease, including environment and ethical issues related to the ongoing coronavirus disease 2019 infection. Vranckx, P (corresponding author), Jessaziekenhuis Hasselt, Dept Cardiol & Intens Care, Stadsomvaart 11, B-3500 Hasselt, Belgium. pascal.vranckx@iccuhasselt.be

Background: COVID-19 syndrome is a world-wide pandemic with multiple international publications demonstrating mortality for those admitted to intensive care to be between 46 – 88%. The experience at Chelsea & Westminster’s hospital has been dramatically different from those reported with a mortality of 24·4%. We sought to analyse this difference retrospectively in a case-cohort study. Methods: Whole case of 16 non-survivors with 15 closely matched survivors (age and APACHE-II) were analysed and compared to UK national published data. Patients trajectories were aligned according to the lowest PaO2/FiO2 ratio. Lymphocyte count, ferritin and organ support data were also aligned to PaO2/FiO2 ratio to demonstrate trends in patient trajectories. Findings: Following alignment, patient trajectories were in opposition to aggregated population data suggesting Simpson’s paradox is present in COVID-19 mortality data; a form of confounding. Population based data suggests that patients’s respiratory function declines till death but following alignment, it is shown that respiratory function and lymphocytes recover prior to death. Importance: Data from this study suggests that the day 10 – 15 nadir in respiratory function will improve. Consideration of withdrawal of care should be based on individual cases as aggregated data is misleading and late recovery may occur. Funding Statement: None applicable. Declaration of Interests: None declared by all authors. Ethics Approval Statement: The study was approved by the Chelsea and Westminster NHS Foundation Trust clinical governance team. As the report involves routinely collected non-identifiable clinical audit data, no ethical approval was required under the UK policy framework for health and social care.

Background: Ventilator-associated pneumonia is the most common intensive care unit (ICU)-acquired infection, yet accurate diagnosis remains difficult, leading to overuse of antibiotics. Low concentrations of IL-1β and IL-8 in bronchoalveolar lavage fluid have been validated as effective markers for exclusion of ventilator-associated pneumonia. The VAPrapid2 trial aimed to determine whether measurement of bronchoalveolar lavage fluid IL-1β and IL-8 could effectively and safely improve antibiotic stewardship in patients with clinically suspected ventilator-associated pneumonia.Methods: VAPrapid2 was a multicentre, randomised controlled trial in patients admitted to 24 ICUs from 17 National Health Service hospital trusts across England, Scotland, and Northern Ireland. Patients were screened for eligibility and included if they were 18 years or older, intubated and mechanically ventilated for at least 48 h, and had suspected ventilator-associated pneumonia. Patients were randomly assigned (1:1) to biomarker-guided recommendation on antibiotics (intervention group) or routine use of antibiotics (control group) using a web-based randomisation service hosted by Newcastle Clinical Trials Unit. Patients were randomised using randomly permuted blocks of size four and six and stratified by site, with allocation concealment. Clinicians were masked to patient assignment for an initial period until biomarker results were reported. Bronchoalveolar lavage was done in all patients, with concentrations of IL-1β and IL-8 rapidly determined in bronchoalveolar lavage fluid from patients randomised to the biomarker-based antibiotic recommendation group. If concentrations were below a previously validated cutoff, clinicians were advised that ventilator-associated pneumonia was unlikely and to consider discontinuing antibiotics. Patients in the routine use of antibiotics group received antibiotics according to usual practice at sites. Microbiology was done on bronchoalveolar lavage fluid from all patients and ventilator-associated pneumonia was confirmed by at least 104 colony forming units per mL of bronchoalveolar lavage fluid. The primary outcome was the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage. Data were analysed on an intention-to-treat basis, with an additional per-protocol analysis that excluded patients randomly assigned to the intervention group who defaulted to routine use of antibiotics because of failure to return an adequate biomarker result. An embedded process evaluation assessed factors influencing trial adoption, recruitment, and decision making. This study is registered with ISRCTN, ISRCTN65937227, and ClinicalTrials.gov, NCT01972425.Findings: Between Nov 6, 2013, and Sept 13, 2016, 360 patients were screened for inclusion in the study. 146 patients were ineligible, leaving 214 who were recruited to the study. Four patients were excluded before randomisation, meaning that 210 patients were randomly assigned to biomarker-guided recommendation on antibiotics (n=104) or routine use of antibiotics (n=106). One patient in the biomarker-guided recommendation group was withdrawn by the clinical team before bronchoscopy and so was excluded from the intention-to-treat analysis. We found no significant difference in the primary outcome of the distribution of antibiotic-free days in the 7 days following bronchoalveolar lavage in the intention-to-treat analysis (p=0·58). Bronchoalveolar lavage was associated with a small and transient increase in oxygen requirements. Established prescribing practices, reluctance for bronchoalveolar lavage, and dependence on a chain of trial-related procedures emerged as factors that impaired trial processes.Interpretation: Antibiotic use remains high in patients with suspected ventilator-associated pneumonia. Antibiotic stewardship was not improved by a rapid, highly sensitive rule-out test. Prescribing culture, rather than poor test performance, might explain this absence of effect.Funding: UK Department of Health and the Wellcome Trust.

Inhaled medications are the cornerstone of therapy for chronic obstructive pulmonary disease (COPD) patients, yet ∼1/3 of patients make critical errors when using their inhaler devices that can impact on therapeutic benefit. The UK Inhaler Group (UKIG), surveyed their member organisations and identified 5 themes of concern potentially affecting patients’ use of inhalers: (1) patient training and knowledge of their inhalers, (2) inhalers in the acute emergency, (3) environmental issues, (4) spacer use and (5) inhalers in schools. The aims of this study were to assess patients’ knowledge regarding use of their inhaler devices and gauge their opinions on inhalers in order to examine patient-relevant factors that influence use of their inhaled medication. COPD patients (n=138) were individually interviewed before their clinic appointment at a tertiary care centre. A 47-item questionnaire was devised to explore patients’ knowledge and opinions related to their inhalers, and their understanding regarding inhaler themes (2 - 5). Patients’ knowledge on inhaler use was found lacking in themes (1 - 4). Of concern, 55/138 (40%) of patients had not had their inhaler technique reviewed by a healthcare professional (HCP) in the last 12 months, demonstrating a clear risk of deterioration in inhaler technique. 90/138 (65%) of patients had not been shown how to use their inhaler for when they had breathing difficulty in an acute emergency. 24/138 (17%) of patients demonstrated knowledge of environmental issues specific to inhalers. In terms of spacer use, interestingly 74/121 (61%) of patients were unable to explain why a spacer was useful. Understanding the accessibility of inhalers in schools was difficult to gauge as these were COPD rather than asthma patients; however universally high ratings of importance were given to the presence of inhalers in schools. Patients’ knowledge in inhaler use is inconsistent and lacking. Importantly, the lack of regular inhaler technique review by HCPs exposes a risk to patient health and contributes to the prevailing critical errors observed. Our data shows that deficiencies of patient knowledge in the main themes identified, particularly in the use of inhalers in an emergency, highlight significant concerns and the need for action to be taken.

Background Restrictions on respiratory trainee time and access to procedures reduce the opportunities to acquire necessary skills in bronchoscopy. Simulation, not subject to such impediments, is a useful supplementary aid to teaching bronchoscopic techniques in a safe environment but there is a limited choice of simulators that are sufficiently realistic and not prohibitively expensive. This study evaluated a low-cost device that simulates an intubated and ventilated patient, employing re-useable, inflatable, BioFlex-preserved, porcine lungs. Methods 26 bronchoscopists, trainee and experienced, after using the bronchoscopy biosimulator, completed a questionnaire using a five-point Likert scale comparing its performance with that of the computerised CAE AccuTouch. Results Participants were largely positive about their experience (mean score of 4.76). The bronchoscopy biosimulator was found to be realistic (mean score 4.64), easy to use (mean score 4.88), and helpful in learning to perform a variety of diagnostic and therapeutic procedures (mean score 4.85). Importantly, the bronchoscopy biosimulator compared favourably to the computer simulator (mean score 4.84). Conclusions These data support the concept of the bronchoscopy biosimulator as an acceptable model with which to supplement the experience of bronchoscopic procedures., A re-useable bronchoscopy biosimulator with ventilated lungs hones skills in an environment that is realistic, is free of patient safety issues and time constraints, and provides a complementary training tool to commercially available simulation models http://ow.ly/AkWM30octSd

Comprehensive echocardiography assessment of right ventricular (RV) impairment has not been reported in critically ill patients with COVID-19. We detail the specific phenotype and clinical associations of RV impairment in COVID-19 acute respiratory distress syndrome (ARDS).Transthoracic echocardiography (TTE) measures of RV function were collected in critically unwell patients for associations with clinical, ventilatory and laboratory data.Ninety patients (25.6% female), mean age 52.0 ± 10.8 years, veno-venous extracorporeal membrane oxygenation (VVECMO) (42.2%) were studied. A significantly higher proportion of patients were identified as having RV dysfunction by RV fractional area change (FAC) (72.0%,95% confidence interval (CI) 61.0-81.0) and RV velocity time integral (VTI) (86.4%, 95 CI 77.3-93.2) than by tricuspid annular plane systolic excursion (TAPSE) (23.8%, 95 CI 16.0-33.9), RVS' (11.9%, 95% CI 6.6-20.5) or RV free wall strain (FWS) (35.3%, 95% CI 23.6-49.0). RV VTI correlated strongly with RV FAC (p ≤ 0.01). Multivariate regression demonstrated independent associations of RV FAC with NTpro-BNP and PVR. RV-PA coupling correlated with PVR (univariate p 0.01), as well as RVEDAi (p 0.01), and RVESAi (p 0.01), and was associated with P/F ratio (p 0.026), PEEP (p 0.025), and ALT (p 0.028).Severe COVID-19 ARDS is associated with a specific phenotype of RV radial impairment with sparing of longitudinal function. Clinicians should avoid interpretation of RV health purely on long-axis parameters in these patients. RV-PA coupling potentially provides important additional information above standard measures of RV performance in this cohort.

BackgroundDemographic data show an increasingly aging human immunodeficiency virus (HIV) population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older people living with HIV (PLWH). We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50 mg once daily in PLWH aged 60 and older. Additionally, to address calls for prospective neuropsychiatric toxicodynamic data, we evaluated changes in sleep quality and cognitive functioning in this population after switching to abacavir (ABC)/lamivudine (3TC)/DTG over 6 months.MethodsPLWH ≥60 years with HIV-viral load ResultsIn total, 43 participants enrolled, and 40 completed the PK phase. Overall, 5 discontinued (2 due to sleep-related adverse events, 4.6%). DTG maximum concentration (Cmax) was significantly higher in patients ≥60 years old versus controls (geometric mean 4246 ng/mL versus 3402 ng/mL, P = .005). In those who completed day 180 (n = 38), sleep impairment (Pittsburgh Sleep Quality Index) was marginally higher at day 28 (P = .02), but not at days 90 or 180. Insomnia, daytime functioning, and fatigue test scores did not change statistically over time.ConclusionsDTG Cmax was significantly higher in older PLWH. Our data provides clinicians with key information on the safety of prescribing DTG in older PLWH.

Tracheobronchopathia osteochondroplastica (TO) is a large airway disorder, characterised by bony nodule growth on the anterior and lateral walls of the trachea and bronchi. Its diagnosis is based on the ‘rock garden’ appearance on bronchoscopy.[1–3][1] However, as an uncommon condition with

Antibiotic use in intensive care units (ICUs) can promote antimicrobial resistance. Outbreaks of multi-resistant bacteria significantly affect patient outcomes and delivery of care. Antibiotic stewardship programmes (ASPs), combining root-cause analyses and multi-faceted prevention strategies, are necessary, often at significant cost and time. Which elements of such strategies have the largest impact on antibiotic usage following an outbreak is unclear. The aim of this study was to investigate how antibiotic usage in a university hospital ICU changed with a non-protocolised ASP following a disruptive outbreak of multi-resistant Acinetobacter baumannii (MRAB). This was a three time-period observational cohort study. The primary endpoint was the change in overall antibiotic usage (daily defined dose, DDD, antibiotic-days, antibiotic-courses) for consecutive ICU patients staying >48 h, over three 6-month study time periods pre-MRAB (2008, n = 84) and post-MRAB (2010, n = 88; 2012, n = 122). Secondary endpoints were changes in antibiotic usage and patient demographics, in predefined admission categories (Medical Emergency, ME; Surgical Elective, SEL; and Surgical Emergency, SE). The mean age (54.6 ± 17.7, 58.1 ± 17.9, 62.8 ± 19.1 years*) and severity of illness (APACHE 14.8 ± 8.0, 16.7 ± 6.8, 18.3 ± 6.1*) increased, particularly medical admissions. There was a sustained reduction in DDD antibiotic usage [1895.1 (2008), 1224.2 (2010), 1236.6 (2012) per 1000 patient-days] but no overall change in antibiotic-days or antibiotic-courses. Antibiotic usage (antibiotic-days) fell significantly in surgical emergency admissions [20.2 ± 32.1, 4.6 ± 7.4*, 5.9 ± 7.3]. There was a sustained drop in beta-lactam, quinolone, glycopeptide and macrolide usage. Following an MRAB outbreak, and subsequent operational changes including enhanced ASPs (non-protocolised), there was a sustained overall fall in antibiotic usage in spite of an increase in disease severity over 5 years.

Purpose This survey investigated current practice in intensive care unit radiology reporting using a survey tool. We ascertained physician attitudes regarding best practice. Methods A national survey was sent by email to a sample of intensive care units throughout UK between March and October 2014. The questionnaire determined current practice in reporting chest X-ray in intensive care units. It also identified differences between ‘routine’ and emergency and out-of-hours service. Further, it investigated how reports were documented and physician preferences for perceived best practice. Results Of 146 intensive care units contacted, 55% completed the survey. Of the sample, radiologists were solely responsible for chest X-ray reporting in 43.7%, intensive care unit clinicians in 33.7% and joint reporting in 25% of intensive care units. The reporting clinician on intensive care unit was a consultant in 67% of the centres. Written reports by radiologists were provided in 71.7% of cases. This was only 54.5% when intensive care unit clinicians reported chest X-rays. For all routine and emergency films, written reports by radiologists occurred in 63.1% of responders. Out-of-hours, 54.9% of clinicians described different reporting practice to normal hours. Regarding perceived best practice, 64.8% of clinicians preferred joint daily reporting, whilst 27% preferred a radiologist’s formal report. For emergencies, 55.2% of the survey recipients preferred a joint report. Conclusion Based on this cohort of UK intensive care units, at present, there appears to be a lack of a standardised system for image reporting. There are discrepancies in who reports chest X-rays, written documentation and the timing of reports, more so out-of-hours. Clinicians suggest that joint reporting should be the standard.

Diagnostic error has implications for both clinical outcome and resource utilisation, and may often be traced to impaired data gathering, processing or synthesis because of the influence of cognitive bias. Factors inherent to the intensive/acute care environment afford multiple additional opportunities for such errors to occur. This article illustrates many of these with reference to a case encountered on our intensive care unit. Strategies to improve completeness of data gathering, processing and synthesis in the acute care environment are critically appraised in the context of early detection and amelioration of cognitive bias. These include reflection, targeted simulation training and the integration of social media and IT based aids in complex diagnostic processes. A framework which can be quickly and easily employed in a variety of clinical environments is then presented.

According to the British Thoracic Society (BTS) guidelines,[1][1] extracorporeal membrane oxygenation (ECMO) may be considered in near-fatal asthma exacerbations refractory to conventional ventilator treatment. However, there is currently no clear criteria for accepting such patients for ECMO

Owing to complexities of measuring dead space, ventilatory failure is difficult to quantify in critical care. A simple, novel index called ventilatory ratio (VR) can quantify ventilatory efficiency at the bedside. The study objectives were to evaluate physiological properties of VR and examine its clinical applicability in acute respiratory distress syndrome (ARDS) patients.A validated computational model of cardiopulmonary physiology [Nottingham Physiology Simulator (NPS)] was used to evaluate VR ex vivo in three virtual patients with varying degrees of gas exchange defects. Arterial P(CO₂) and mixed expired P(CO₂) were obtained from the simulator while either dead space or CO₂ production was altered in isolation. VR and deadspace fraction was calculated using these values. A retrospective analysis of a previously presented prospective ARDS database was then used to evaluate the clinical utility of VR. Basic characteristics of VR and its association with mortality were examined.The NPS showed that VR behaved in an intuitive manner as would be predicted by its physiological properties. When CO₂ production was constant, there was strong positive correlation between dead space and VR (modified Pearson's r 0.98, P0.01). The ARDS database had a mean VR of 1.47 (standard deviation 0.58). Non-survivors had a significantly higher VR compared with survivors [1.70 vs 1.34, mean difference 0.35, 95% confidence interval (CI) 0.16-0.56, P0.01]. VR was an independent predictor of mortality (odds ratio 3.05, CI 1.35-6.91, P0.01).VR is influenced by dead space and CO₂ production. In ARDS, high VR was associated with increased mortality.

Tracheal rupture is an infrequent, severe complication of endotracheal intubation, which can be difficult to diagnose. Post-intubation tracheal rupture (PiTR) is distinct from non-iatrogenic causes of tracheobronchial trauma and often requires different treatment. The increasing adoption of pre-hospital emergency services increases the likelihood of such complications from emergency intubations. Effective management strategies for PiTR outside specialist cardiothoracic units are possible. Two cases of severe PiTR, successfully managed non-operatively on a general medical-surgical intensive care unit, illustrate a modified approach to current standards. The evidence base for PiTR is reviewed and a pragmatic management algorithm presented.

Ventilator-acquired pneumonia (VAP) is a common reason for antimicrobial therapy in the intensive care unit (ICU). Biomarker-based diagnostics could improve antimicrobial stewardship through rapid exclusion of VAP. Bronchoalveloar lavage (BAL) fluid biomarkers have previously been shown to allow the exclusion of VAP with high confidence. This is a prospective, multi-centre, randomised, controlled trial to determine whether a rapid biomarker-based exclusion of VAP results in fewer antibiotics and improved antimicrobial management. Patients with clinically suspected VAP undergo BAL, and VAP is confirmed by growth of a potential pathogen at > 104 colony-forming units per millilitre (CFU/ml). Patients are randomised 1:1, to either a ‘biomarker-guided recommendation on antibiotics’ in which BAL fluid is tested for IL-1β and IL-8 in addition to routine microbiology testing, or to ‘routine use of antibiotics’ in which BAL undergoes routine microbiology testing only. Clinical teams are blinded to intervention until 6 hours after randomisation, when biomarker results are reported to the clinician. The primary outcome is a change in the frequency distribution of antibiotic-free days (AFD) in the 7 days following BAL. Secondary outcome measures include antibiotic use at 14 and 28 days; ventilator-free days; 28-day mortality and ICU mortality; sequential organ failure assessment (SOFA) at days 3, 7 and 14; duration of stay in critical care and the hospital; antibiotic-associated infections; and antibiotic-resistant pathogen cultures up to hospital discharge, death or 56 days. A healthcare-resource-utilisation analysis will be calculated from the duration of critical care and hospital stay. In addition, safety data will be collected with respect to performing BAL. A sample size of 210 will be required to detect a clinically significant shift in the distribution of AFD towards more patients having fewer antibiotics and therefore more AFD. This trial will test whether a rapid biomarker-based exclusion of VAP results in rapid discontinuation of antibiotics and therefore improves antibiotic management in patients with suspected VAP. ISRCTN65937227 . Registered on 22 August 2013. ClinicalTrials.gov, NCT01972425 . Registered on 24 October 2013.

The aim of history and examination is to facilitate clinical diagnosis. Using the hypothetico-deductive method of diagnosis based upon Bayes' theorem, a detailed history and competent examination skills are essential for accurate diagnosis. The key symptoms of respiratory disease are breathlessness, chest pain, wheeze, cough and associated sputum production. However, non-respiratory conditions may produce such symptoms. Furthermore, the lungs can also produce non-respiratory symptoms (e.g. paraneoplastic syndromes). A systematic approach to history-taking should include all primary symptoms, with their time-course, characteristics and severity. A review of non-respiratory associations, drug exposure and historical aspects of respiratory symptoms is followed by a thorough examination. Further clarification of clinical features, and assimilation of information allows formulation of a differential diagnosis. On examination, there are a few classical patterns of the most important focal abnormalities, yet there may be an absence of clinical signs.

Diagnosis of mediastinal/hilar lymph nodes and peribronchial masses | || | Conventional transbronchial fine needle aspiration (TBNA) | | B | | | √ | | | Endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-TBNA) | | B | | | D | | | √ | | | Therapeutic procedures for malignant disease | | Malignant airway obstruction | | 1. Endobronchial debulking of tumours | | D | | | √ | | | 2. Endobronchial electrocautery or diathermy | | D | | | √ |

Summary Inhalation injury may result from numerous noxious triggers and in association with other injuries, the most common being cutaneous burns. While patients with severe burns often require transfer to a regional unit for specialist management, this is not the case for those with inhalation injury associated with minor burns or occurring in isolation. These latter patients may require management in a general intensive care unit and yet they present some unique challenges to the clinician that may otherwise go unnoticed. The aim of this review is to provide an overview of the pathophysiology, presentation and management of patients with inhalation injury by way of a guide to those who manage such patients on an infrequent basis.

BackgroundThere is a clinical need for therapeutic options to reduce hyperinflation associated with severe emphysema. Endobronchial Coils (coils) are nitinol devices implanted bronchoscopically under fluoroscopic guidance to re-tension the lung. We report the medium term effectiveness and safety of coils in a study of patients with emphysema.MethodsForty five subjects with severe airflow obstruction and hyperinflation received bilateral sequential treatment with coils (30 day interval between treatments) as part of a randomised controlled trial with a primary endpoint 90 days after the final treatment (Clinicaltrials.gov NCT01334307). Further assessments were made at 180 and 360 days and in this study the primary outcome was the effect of coil treatment on the St. George's Respiratory Questionnaire (SGRQ) 360 days following treatment.ResultsAt 360 days following treatment, there was an improvement in the SGRQ score of -6.1±14.0 points (p = 0.01) compared to baseline. Improvements in secondary outcomes were seen with increases in forced expiratory volume in the first second of 8.9 ±22.2% (p = 0.002) and 6-minute walking distance of 34.1±52.4m (p = 0.003). The safety profile was acceptable out to 360 days post-treatment.ConclusionsStatistically and clinically meaningful benefits in quality of life, exercise capacity and pulmonary function in patients treated with coils are sustained twelve months after treatment.Trial registration informationClinicaltrials.gov NCT01334307.

Transbronchial fine needle aspiration (TBNA) is a simple technique for sampling mediastinal lymph nodes and may provide additional information in patients with suspected lung cancer. However, the technique is still under-utilized, and the objective of this study was to evaluate the value of TBNA as part of an integrated pathway for the assessment of patients with suspected lung cancer. All patients referred to the lung cancer services of our institutions were prospectively evaluated. TBNA was performed in all patients with evidence of mediastinal lymphadenopathy. TBNA of one or more lymph node sites were performed in 129 of these patients. TBNA was the sole diagnostic modality in 23% of patients and provided positive staging information for 49% of patients, with adequate sampling in 71% of patients. Among patients with mediastinal adenopathy, the number of patients who required a TBNA performed to diagnose one patient with malignancy in patients suspected with lung cancer (number needed to diagnose) was 1.47 (95% confidence interval, 1.47–1.76). No complications were observed in patients who underwent TBNA. TBNA improves the diagnostic yield and staging of patients with lung cancer. Moreover, it is a simple, low-cost, and safe test, which should be incorporated into the diagnostic pathway of patients with suspected lung cancer.

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

Background: Excessive use of empirical antibiotics is common in critically ill patients. Rapid biomarker-based exclusion of infection may improve antibiotic stewardship in ventilator-acquired pneumonia (VAP). However, successful validation of the usefulness of potential markers in this setting is exceptionally rare.Objectives: We sought to validate the capacity for specific host inflammatory mediators to exclude pneumonia in patients with suspected VAP. Methods: A prospective, multicentre, validation study of patients with suspected VAP was conducted in 12 intensive care units. VAP was confirmed following bronchoscopy by culture of a potential pathogen in bronchoalveolar lavage fluid (BALF) at >104 colony forming units per millilitre (cfu/mL). Interleukin-1 beta (IL-1β), IL-8, matrix metalloproteinase-8 (MMP-8), MMP-9 and human neutrophil elastase (HNE) were quantified in BALF. Diagnostic utility was determined for biomarkers individually and in combination. Results: Paired BALF culture and biomarker results were available for 150 patients. 53 patients (35%) had VAP and 97 (65%) patients formed the non-VAP group. All biomarkers were significantly higher in the VAP group (pConclusions: Low BALF IL-1β in combination with IL-8 confidently excludes VAP and could form a rapid biomarker-based rule-out test, with the potential to improve antibiotic stewardship.

Background and Objectives: The bronchoscopic microsample (BMS) probe allows direct epithelial lining fluid (ELF) level measurement without saline lavage. We investigated whether cytokine levels in ELF from a BMS differed from those obtained by bronchoalveolar lavage (BAL) in stable and acute lung disease. Methods: In a single-centre, prospective observational cohort study of 45 patients, a sequential BMS probe procedure and BAL were performed on patients with stable chronic obstructive lung disease, interstitial lung disease, acute lung injury (ALI), burns-related inhalational injury or controls. ELF samples were assayed for IL-1β, IL-6, IL-8, TNF-α and G-CSF. Results: Both bronchoscopic microsampling and BAL showed significantly higher cytokine levels in the ELF from patients with ALI and burns-related inhalational injury than from those with chronic stable lung disease. The BMS method detected cytokine levels approximately 20- to 80-fold higher than the corresponding BAL (uncorrected for dilution). The ratio of BMS and BAL cytokine levels was as follows: the ratio for IL-1β [mean 55, 95% confidence interval (CI) 34-88] was higher than that for IL-6 (mean 16, 95% CI 10-23, p = 0.015) and IL-8 (mean 13, 95% CI -5 to 36, p = 0.03). The ratio for G-CSF (mean 43, 95% CI 24-75) was higher than that for IL-6 (mean 16, 95% CI 10-23, p = 0.008). Conclusions: The BMS probe safely collects ELF with higher equivalent inflammatory cytokine concentrations than via BAL from patients with both acute and chronic lung disease and can be an alternative to saline BAL. Variations in cytokine concentrations between BMS and BAL and sampling-site differences warrant further study.