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Supplemental Digital Content is available in the text., OBJECTIVES: Several studies have reported prone positioning of nonintubated patients with coronavirus diseases 2019–related hypoxemic respiratory failure. This systematic review and meta-analysis evaluated the impact of prone positioning on oxygenation and clinical outcomes. DESIGN AND SETTING: We searched PubMed, Embase, and the coronavirus diseases 2019 living systematic review from December 1, 2019, to November 9, 2020. SUBJECTS AND INTERVENTION: Studies reporting prone positioning in hypoxemic, nonintubated adult patients with coronavirus diseases 2019 were included. MEASUREMENTS AND MAIN RESULTS: Data on prone positioning location (ICU vs non-ICU), prone positioning dose (total minutes/d), frequency (sessions/d), respiratory supports during prone positioning, relative changes in oxygenation variables (peripheral oxygen saturation, Pao2, and ratio of Pao2 to the Fio2), respiratory rate pre and post prone positioning, intubation rate, and mortality were extracted. Twenty-five observational studies reporting prone positioning in 758 patients were included. There was substantial heterogeneity in prone positioning location, dose and frequency, and respiratory supports provided. Significant improvements were seen in ratio of Pao2 to the Fio2 (mean difference, 39; 95% CI, 25–54), Pao2 (mean difference, 20 mm Hg; 95% CI, 14–25), and peripheral oxygen saturation (mean difference, 4.74%; 95% CI, 3–6%). Respiratory rate decreased post prone positioning (mean difference, –3.2 breaths/min; 95% CI, –4.6 to –1.9). Intubation and mortality rates were 24% (95% CI, 17–32%) and 13% (95% CI, 6–19%), respectively. There was no difference in intubation rate in those receiving prone positioning within and outside ICU (32% [69/214] vs 33% [107/320]; p = 0.84). No major adverse events were recorded in small subset of studies that reported them. CONCLUSIONS: Despite the significant variability in frequency and duration of prone positioning and respiratory supports applied, prone positioning was associated with improvement in oxygenation variables without any reported serious adverse events. The results are limited by a lack of controls and adjustments for confounders. Whether this improvement in oxygenation results in meaningful patient-centered outcomes such as reduced intubation or mortality rates requires testing in well-designed randomized clinical trials.

A combination of pregabalin and tapentadol may be associated with prolonged encephalopathy., A combination of rregabalin and tapentadol may be associated with prolonged encephalopathy.

Background Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. Method This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH Results We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. Conclusions Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Objectives: To compare the characteristics and outcomes of patients presenting to hospital with alcohol-induced and gallstone-induced acute pancreatitis. Methods: Retrospective study of all patients with alcohol-induced or gallstone-induced pancreatitis during the period 1 June 2012 to 31 May 2016. The primary outcome measure was hospital mortality. Secondary outcome measures included hospital length of stay, requirements for intensive care unit admission, intensive care unit mortality, mechanical ventilation, renal replacement therapy, requirement of inotropes and total parenteral nutrition. Results: A total of 642 consecutive patients (49% alcohol; 51% gallstone) were included. No statistically significant differences were found between alcohol-induced and gallstone-induced acute pancreatitis with respect to hospital mortality, requirement for intensive care unit admission, intensive care unit mortality and requirement for mechanical ventilation, renal replacement therapy, inotropes or total parenteral nutrition. There was significant difference in hospital length of stay (3.07 versus 4.84; p Conclusion: Hospital mortality did not differ between patients with alcohol-induced and gallstone-induced acute pancreatitis. The duration of hospital stay was longer with gallstone-induced pancreatitis. Bedside Index of Severity in Acute Pancreatitis score and admission haematocrit were independently associated with hospital length of stay.

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.

Good quality sleep is considered to be essential for healthy living and recovering from illness. It would be logical to think that good quality sleep is most required when a patient is critically ill in an intensive care unit (ICU). Several studies have demonstrated poor quality of sleep while the patients are in ICU. Subjective tools such as questionnaires while simple are unreliable to accurately assess sleep quality. Relatively few studies have used standardized polysomnography. The use of novel biological markers of sleep such as serum brain-derived neurotrophic factor concentrations may help in conjunction with polysomnography to assess sleep quality in critically ill patients. Attempts to improve sleep included nonpharmacological interventions including the use of earplugs, eye sleep masks, and pharmacological agents including ketamine, propofol, dexmedetomidine, and benzodiazepines. The evidence for these interventions remains unclear. Further research is needed to assess quality of sleep and improve the sleep quality in intensive care settings.

The use of lower tidal volume ventilation was shown to improve survival in mechanically ventilated patients with acute lung injury. In some patients this strategy may cause hypercapnic acidosis. A significant body of recent clinical data suggest that hypercapnic acidosis is associated with adverse clinical outcomes including increased hospital mortality. We aimed to review the available treatment options that may be used to manage acute hypercapnic acidosis that may be seen with low tidal volume ventilation. The databases of MEDLINE and EMBASE were searched. Studies including animals or tissues were excluded. We also searched bibliographic references of relevant studies, irrespective of study design with the intention of finding relevant studies to be included in this review. The possible options to treat hypercapnia included optimising the use of low tidal volume mechanical ventilation to enhance carbon dioxide elimination. These include techniques to reduce dead space ventilation, and physiological dead space, use of buffers, airway pressure release ventilation and prone positon ventilation. In patients where hypercapnic acidosis could not be managed with lung protective mechanical ventilation, extracorporeal techniques may be used. Newer, minimally invasive low volume venovenous extracorporeal devices are currently being investigated for managing hypercapnia associated with low and ultra-low volume mechanical ventilation.

Bleomycin is an antibiotic chemotherapy agent with low myelosuppressive properties that is still frequently used for management of Hodgkin's lymphoma and testicular cancer 1, 2, 3, 4. Bleomycin clearance is dependent on bleomycin hydroxylase and the lack of this enzyme in lungs and skin predisposes patients to significant pulmonary toxicity 1, 2, 4. Pulmonary adverse events from bleomycin are some of the most common lung toxicities studied and frequently present as bronchiolitis obliterans with organizing pneumonia (BOOP), eosinophilic hypersensitivity, as well as interstitial pneumonitis with fibrosis 1, 2, 3, 4. Bleomycin interstitial pneumonitis (BIP) has been thought to be caused by direct endothelial damage of the pulmonary vasculature with severe inflammation and stimulation of the immune system, causing acute and chronic inflammation with progression to fibrosis 1, 4. Bleomycin pulmonary toxicity has been associated with significant mortality, particularly in patients receiving concomitant radiation therapy 1, 2, 3, 4. Many risk factors for development of BIP have been proposed and include oxygen therapy, high cumulative doses of bleomycin, renal impairment, smoking, mediastinal radiation therapy, patient age (>40 years), use of colony‐stimulating agents, and the administration method 1, 2, 3, 4. Several agents have been recommended for the management of BIP based on animal study results including interleukin (IL)‐1‐receptor antagonists, anti‐tumor necrosis factor (TNF)‐α antibodies, and inhibitors of transforming growth factor (TGF)‐β 1, 4. Corticosteroids at high doses are frequently used, but are thought to benefit BOOP and eosinophilic hypersensitivity rather than BIP, with the diagnosis of these conditions frequently confused 1. Arsenic trioxide has been trialed in management of BIP as it reduces TGF‐β and its downstream effects on differentiation of fibroblasts as well as type‐1 collagen deposition in pulmonary tissues 5. Similarly, imatinib suppresses the transformation of fibroblasts into myofibroblasts and reduces collagen deposition via inhibition of platelet‐derived growth factor and TGF‐β signaling 6. Arsenic studies have been confined to animal models, while imatinib has not improved outcomes in human studies of idiopathic pulmonary fibrosis (IPF), a condition that shares many biochemical and histological features with BIP 5, 6. A very small number of case studies have been published examining the use of imatinib in BIP and other forms of pulmonary fibrosis, with variable effects on outcome 7, 8, 9, 10, 11. These data were the rationale for using imatinib therapy in our patient.

Hamish Brown,1,* Stefan Dodic,1,* Sheen Sern Goh,2 Cameron Green,3 Wei C Wang,1 Sameer Kaul,4 Ravindranath Tiruvoipati1,3 1Faculty of Medicine, Nursing, and Health Sciences, Monash University, Melbourne, VIC, Australia; 2Department of Medicine, Frankston Hospital, Melbourne, VIC, Australia; 3Department of Intensive Care Medicine, Frankston Hospital, Melbourne, VIC, Australia; 4Department of Respiratory Medicine, Frankston Hospital, Melbourne, VIC, Australia *These authors contributed equally to this work Introduction: COPD is a leading cause of morbidity and mortality worldwide. Patients with COPD often require admission to intensive care units (ICU) during an acute exacerbation. Objective: This study aimed to identify the factors independently associated with hospital mortality in patients requiring ICU admission for acute exacerbation of COPD. Methods: Patients admitted to the ICU of Frankston Hospital between January 2005 and June 2016 with an admission diagnosis of COPD were retrospectively identified from ICU databases. Patients’ comorbidities, arterial blood gas results, and in-patient interventions were retrieved from their medical records. Outcomes analyzed included hospital and ICU length of stay (LOS) and mortality. Results: A total of 305 patients were included. Mean age was 67.4 years. A total of 77% of patients required non-invasive ventilation; and 38.7% required invasive mechanical ventilation (IMV) for a median of 127.2 hours (SD =179.5). Mean ICU LOS was 4.5 days (SD =5.96), and hospital LOS was 11.6 days (SD =13). In-hospital mortality was 18.7%. Multivariate analysis revealed that patient age (odds ratio [OR] =1.06; 95% CI: 1.031–1.096), ICU LOS (OR =1.26; 95% CI: 1.017–1.571), Acute Physiology and Chronic Health Evaluation-II score (OR =1.07; 95% CI: 1.012–1.123), and requirement for IMV (OR =4.09; 95% CI: 1.791–9.324) to be significantly associated with in-hospital mortality. Conclusion: Patient age, requirement for IMV, and illness severity were associated with poor patient outcomes. Keywords: COPD, intensive care, mechanical ventilation, mortality, outcome, critically ill

Background Some patients experience a delayed discharge from the intensive care unit (ICU) where the intended and actual discharge times do not coincide. The clinical implications of this remain unclear. Objective To determine the incidence and duration of delayed ICU discharge, identify the reasons for delay and evaluate the clinical consequences. Methods Prospective multi-centre observational study involving five ICUs over a 3-month period. Delay in discharge was defined as >6 hours from the planned discharge time. The primary outcome measure was hospital length stay after ICU discharge decision. Secondary outcome measures included ICU discharge after-hours, incidence of delirium, survival to hospital discharge, discharge destination, the incidence of ICU acquired infections, revocation of ICU discharge decision, unplanned readmissions to ICU within 72 hours, review of patients admitting team after ICU discharge decision. Results A total of 955 out of 1118 patients discharged were included in analysis. 49.9% of the patients discharge was delayed. The most common reason (74%) for delay in discharge was non-availability of ward bed. The median duration of the delay was 24 hours. On univariable analysis, the duration of hospital stay from the time of ICU discharge decision was significantly higher in patients who had ICU discharge delay (Median days-5 vs 6; p = 0.003). After-hours discharge was higher in patients whose discharge was delayed (34% Vs 10%; p

Background Advanced age is one of the factors that increase mortality in intensive care. Sepsis and multi-organ failure are likely to further increase mortality in elderly patients. We compared the characteristics and outcomes of septic elderly patients (> 65 years) with younger patients (≤ 65 years) and identified factors during the first 24 hours of presentation that could predict mortality in elderly patients. Methods This study was conducted in a Level III intensive care unit with a case mix of medical and surgical patients excluding cardiac and neurosurgical patients. We performed a retrospective review of all septic patients admitted to our ICU between July 2004 and May 2007. In addition to demographics and co-morbidities, physiological and laboratory variables were analysed to identify early predictors of mortality in elderly patients with sepsis. Results Of 175 patients admitted with sepsis, 108 were older than 65 years. Elderly patients differed from younger patients with regard to sex, temperature (37.2°C VS 37.8°C p < 0.01), heart rate, systolic blood pressure, pH, HCO3, potassium, urea, creatinine, APACHE III and SAPS II. The ICU and hospital mortality was significantly higher in elderly patients (10.6% Vs 23.14% (p = 0.04) and 19.4 Vs 35.1 (p = 0.02) respectively). Elderly patients who died in hospital had a significant difference in pH, HCO3, mean blood pressure, potassium, albumin, organs failed, lactate, APACHE III and SAPS II compared to the elderly patients who survived while the mean age and co-morbidities were comparable. Logistic regression analysis identified temperature (OR [per degree centigrade decrease] 0.51; 95% CI 0.306- 0.854; p = 0.010) and SAPS II (OR [per point increase]: 1.12; 95% CI 1.016-1.235; p = 0.02) during the first 24 hours of admission to independently predict increased hospital mortality in elderly patients. Conclusions The mortality in elderly patients with sepsis is higher than the younger patients. Temperature (hypothermia) and SAPS II scores during the first 24 hours of presentation independently predict hospital mortality.

There is a paucity of data about whether our treatment philosophy is different for our patients as compared with what we would have wanted for ourselves, or while acting as surrogate decision-makers for our loved ones.

INTRODUCTION Acinetobacter baumannii is usually associated with respiratory tract, urinary tract and bloodstream infections. Recent reports suggest that it is increasingly causing skin and soft tissue infections. It is also evolving as a multidrug resistant organism that can be difficult to treat. We present a fatal case of multidrug resistant A. baumannii soft tissue infection and review of relevant literature. PRESENTATION OF CASE A 41 year old morbidly obese man, with history of alcoholic liver disease presented with left superficial pre-tibial abrasions and cellulitis caused by multidrug resistant (MDR) A. baumannii . In spite of early antibiotic administration he developed extensive myositis and fat necrosis requiring extensive and multiple surgical debridements. He deteriorated despite appropriate antibiotic therapy and multiple surgical interventions with development of multi-organ failure and died. DISCUSSION Managing Acinetobacter infections remains difficult due to the array of resistance and the pathogens ability to develop new and ongoing resistance. The early diagnosis of necrotizing soft tissue infection may be challenging, but the key to successful management of patients with necrotizing soft tissue infection are early recognition and complete surgical debridement. CONCLUSION A. baumannii is emerging as an important cause of severe, life-threatening soft tissue infections. Multidrug resistant A. baumannii soft tissue infections may carry a high mortality in spite of early and aggressive treatment. Clinicians need to consider appropriate early empirical antibiotic coverage or the use of combination therapy to include MDR A. baumannii as a cause of skin and soft tissue infections.

Background Veno-arterial extracorporeal membrane oxygenation (ECMO) is a common modality of circulatory assist device used in children. We assessed the outcome of children who had ECMO following repair of congenital cardiac defects (CCD) and identified the risk factors associated with hospital mortality. Methods From April 1990 to December 2003, 53 patients required ECMO following surgical correction of CCD. Retrospectively collected data was analyzed with univariate and multivariate logistic regression analysis. Results Median age and weight of the patients were 150 days and 5.4 kgs respectively. The indications for ECMO were low cardiac output in 16, failure to wean cardiopulmonary bypass in 13, cardiac arrest in 10 and cardio-respiratory failure in 14 patients. The mean duration of ECMO was 143 hours. Weaning off from ECMO was successful in 66% and of these 83% were survival to hospital-discharge. 37.7% of patients were alive for the mean follow-up period of 75 months. On univariate analysis, arrhythmias, ECMO duration >168 hours, bleeding complications, renal replacement therapy on ECMO, arrhythmias and cardiac arrest after ECMO were associated with hospital mortality. On multivariate analysis, abnormal neurology, bleeding complications and arrhythmias after ECMO were associated with hospital mortality. Extra and intra-thoracic cannulations were used in 79% and 21% of patients respectively and extra-thoracic cannulation had significantly less bleeding complications (p = 0.031). Conclusion ECMO provides an effective circulatory support following surgical repair of CCD in children. Extra-thoracic cannulation is associated with less bleeding complications. Abnormal neurology, bleeding complications on ECMO and arrhythmias after ECMO are poor prognostic indicators for hospital survival.

Background Extracorporeal Membrane Oxygenation (ECMO) is a technology used in treatment of patients with severe but potentially reversible respiratory failure. A multi-centre randomised controlled trial (CESAR) was funded in the UK to compare care including ECMO with conventional intensive care management. The protocol and funding for the CESAR trial included plans for economic data collection and analysis. Given the high cost of treatment, ECMO is considered an expensive technology for many funding systems. However, conventional treatment for severe respiratory failure is also one of the more costly forms of care in any health system. Methods/Design The objectives of the economic evaluation are to compare the costs of a policy of referral for ECMO with those of conventional treatment; to assess cost-effectiveness and the cost-utility at 6 months follow-up; and to assess the cost-utility over a predicted lifetime. Resources used by patients in the trial are identified. Resource use data are collected from clinical report forms and through follow up interviews with patients. Unit costs of hospital intensive care resources are based on parallel research on cost functions in UK NHS intensive care units. Other unit costs are based on published NHS tariffs. Cost effectiveness analysis uses the outcome: survival without severe disability. Cost utility analysis is based on quality adjusted life years gained based on the Euroqol EQ-5D at 6 months. Sensitivity analysis is planned to vary assumptions about transport costs and method of costing intensive care. Uncertainty will also be expressed in analysis of individual patient data. Probabilities of cost effectiveness given different funding thresholds will be estimated. Discussion In our view it is important to record our methods in detail and present them before publication of the results of the trial so that a record of detail not normally found in the final trial reports can be made available in the public domain. Trial Registrations The CESAR trial registration number is ISRCTN47279827.