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Purpose:Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFRT790M-negative resistance.Experimental Design:We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M+) and -negative (T790M−) disease.Results:Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M− tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M− tumors. Almost half of resistant tumors were further classified as immunehot, with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M− and T790M+ disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients.Conclusions:Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in EGFR-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential.

Supplementary Data from Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities

Background Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. Method and results This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). Conclusions Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.

Therapeutic plasma exchange (TPE) and continuous kidney replacement therapy (CKRT) are extracorporeal therapeutic procedures often implemented in management of patients. Critically ill patients may be afflicted with disease processes that require both TPE and CKRT. Performing TPE discontinuous with CKRT is technically easier, however, it disrupts CKRT and may compromise with CKRT efficiency or hemofilter life. Concurrent TPE with CKRT offers several advantages including simultaneous control of disease process and correction of electrolyte, fluid, and acid-base disturbances that may accompany TPE. Additionally, TPE may be performed by either centrifugation method or membrane plasma separation method. The technical specifications of these methods may influence the methodology of concurrent connections. This report describes and reviews two different approaches to circuit arrangements when establishing concurrent TPE and CKRT.

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a known sequela after acute pulmonary embolism (PE). It is a debilitating disease, and potentially fatal if left untreated. This review provides a clinically relevant overview of the disease and discusses the usefulness and limitations of the various investigational and treatment options. Methods: A PubMed search on articles relevant to pulmonary embolism, pulmonary hypertension, chronic thromboembolic pulmonary hypertension, pulmonary endarterectomy, and balloon pulmonary angioplasty were performed. A total of 68 articles were found to be relevant and were reviewed. Results: CTEPH occurs as a result of non-resolution of thrombotic material, with subsequent fibrosis and scarring of the pulmonary arteries. Risk factors have been identified, but the underlying mechanisms have yet to be fully elucidated. The cardinal symptom of CTEPH is dyspnoea on exertion, but the diagnosis is often challenging due to lack of awareness. The ventilation/perfusion scan is recommended for screening for CTEPH, with other modalities (eg. dual energy computed tomography pulmonary angiography) also being utilised in expert centres. Conventional pulmonary angiography with right heart catherisation is important in the final diagnosis of CTEPH. Conclusion: Operability assessment by a multidisciplinary team is crucial for the management of CTEPH, as pulmonary endarterectomy (PEA) remains the guideline recommended treatment and has the best chance of cure. For inoperable patients or those with residual disease post-PEA, medical therapy or balloon pulmonary angioplasty are potential treatment options. Keywords: Balloon pulmonary angioplasty, Chronic thromboembolic pulmonary hypertension, Pulmonary embolism, Pulmonary endarterectomy, Pulmonary hypertension

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in the city of Wuhan in Mainland China has spread across the globe with >100,000 infected individuals and 3000 deaths reported in 93 countries as of 7 March 2020. We report a case of COVID-19 infection in a 64-year-old man who developed rapidly worsening respiratory failure and acute respiratory distress syndrome (ARDS) that required intubation. As the clinical spectrum of COVID-19 infection ranges from mild illness to ARDS with high mortality risk, there is need for research that identifies early markers of disease severity. Current evidence suggests that patients with advanced age, dyspnoea or pre-existing comorbidities should be monitored closely, especially at 1–2 weeks after symptom onset. It remains to be seen whether laboratory findings such as lymphopaenia or elevated lactate dehydrogenase may serve as early surrogates for critical illness or markers of disease recovery. Management of ARDS in COVID-19 patients remains supportive while we await results of drug trials. More studies are needed to understand the incidence and outcomes of ARDS and critical illness from COVID-19 infection which are important for critical care management of patients and resource planning. Key words: Intensive Care, Mortality, Pneumonia, Risk factors

Introduction: A second-tier rapid response team (RRT) is activated for patients who do not respond to first-tier measures. The premise of a tiered response is that first-tier responses by a ward team may identify and correct early states of deterioration or establish goals of care, thereby reducing unnecessary escalation of care to the RRT. Currently, utilisation and outcomes of tiered RRTs remain poorly described. Methods: A prospective observational study of adult patients (age ≥18 years) who required RRT activations was conducted from February 2018 to December 2019. Results: There were 951 consecutive RRT activations from 869 patients and 76.0% patients had a National Early Warning Score (NEWS) ≥5 at the time of RRT activation. The majority (79.8%) of patients required RRT interventions that included endotracheal intubation (12.7%), point-of-care ultrasound (17.0%), discussing goals of care (14.7%) and intensive care unit (ICU) admission (24.2%). Approximately 1 in 3 (36.6%) patients died during hospitalisation or within 30 days of RRT activation. In multivariate analysis, age ≥65 years, NEWS ≥7, ICU admission, longer hospitalisation days at RRT activation, Eastern Cooperative Oncology Group performance scores ≥3 (OR [odds ratio] 2.24, 95% CI [confidence interval] 1.45–3.46), metastatic cancer (OR 2.64, 95% CI 1.71–4.08) and haematological cancer (OR 2.78, 95% CI 1.84–4.19) were independently associated with mortality. Conclusion: Critical care interventions and escalation of care are common with second-tier RRTs. This supports the need for dedicated teams with specialised critical care services. Poor functional status, metastatic and haematological cancer are significantly associated with mortality, independent of age, NEWS and ICU admission. These factors should be considered during triage and goals of care discussion. Keywords: Clinical deterioration, critical care, intensive care, mortality, rapid response system, rapid response team

Background: There is an increasing frequency of oncology and hematopoietic stem cell transplant (HSCT) patients seen in the intensive care unit and requiring extracorporeal membrane oxygenation (ECMO), however, prognosis of this population over time is unclear. Methods: MEDLINE, EMBASE, Cochrane and Web of Science were searched from earliest publication until April 10, 2020 for studies to determine the mortality trend over time in oncology and HSCT patients requiring ECMO. Primary outcome was hospital mortality. Random-effects meta-analysis model was used to obtain pooled estimates of mortality and 95% confidence intervals. A priori subgroup metanalysis compared adult versus pediatric, oncology versus HSCT, hematological malignancy versus solid tumor, allogeneic versus autologous HSCT, and veno-arterial versus veno-venous ECMO populations. Multivariable meta-regression was also performed for hospital mortality to account for year of study and HSCT population. Results: 17 eligible observational studies (n = 1109 patients) were included. Overall pooled hospital mortality was 72% (95% CI: 65, 78). In the subgroup analysis, only HSCT was associated with a higher hospital mortality compared to oncology subgroup [84% (95% CI: 70, 93) vs. 66% (95% CI: 56, 74); P = 0.021]. Meta-regression showed that HSCT was associated with increased mortality [adjusted odds ratio (aOR) 3.84 (95% CI 1.77, 8.31)], however, mortality improved with time [aOR 0.92 (95% CI: 0.85, 0.99) with each advancing year]. Conclusion: This study reports a high overall hospital mortality in oncology and HSCT patients on ECMO which improved over time. The presence of HSCT portends almost a 4-fold increased risk of mortality and this finding may need to be taken into consideration during patient selection for ECMO.

Patients with COVID-19 infection have an increased risk of cardiovascular complications and thrombotic events. Statins are known for their pleiotropic anti-inflammatory, antithrombotic and immunomodulatory effects. They may have a potential role as adjunctive therapy to mitigate endothelial dysfunction and dysregulated inflammation in patients with COVID-19 infection.

BACKGROUND In solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients, coronavirus disease 2019 (COVID-19) can contribute to a severe clinical course and an increased risk of death. Thus, patients awaiting a SOT or HSCT face the dilemma of choosing between a life-saving treatment that presents a significant threat of COVID-19 and the risk of waitlist dropout, progression of disease, or mortality. The lack of established literature on COVID-19 complicates the issue as patients, particularly those with inadequate health literacy, may not have the resources needed to navigate these decisions. MATERIAL AND METHODS We conducted a standardized phone survey of patients awaiting SOT or HSCT to assess the prevalence of inadequate health literacy and attitudes toward transplant during the COVID-19 pandemic. RESULTS Seventy-one patients completed the survey, with a response rate of 84.5%. Regardless of health literacy, most waitlisted candidates recognized that the current pandemic is a serious situation affecting their care and that COVID-19 poses a significant risk to their health. Despite the increased risks, most patients reported they would choose immediate transplantation if there was no foreseeable end to the pandemic, and especially if the medical urgency did not permit further delay. There were no differences in responses across the patient waitlist groups for heart, kidney, liver, and stem cell transplant. CONCLUSIONS These findings can help transplant centers decide how transplantation services should proceed during this pandemic and can be used to educate patients and guide discussions about informed consent for transplant during the COVID-19 pandemic.

Background The ROX index (ratio of pulse oximetry/FIO2 to respiratory rate) has been validated to predict high flow nasal cannula therapy (HFNC) outcomes in patients with pneumonia. We evaluated a modified ROX index incorporating heart rate (HR) in patients initiated on HFNC for acute hypoxemic respiratory failure and as a preventative treatment following planned extubation. Methods We performed a prospective observational cohort study of 145 patients treated with HFNC. ROX-HR index was defined as the ratio of ROX index over HR (beats/min), multiplied by a factor of 100. Evaluation was performed using area under the receiving operating characteristic curve (AUROC) and cutoffs assessed for prediction of HFNC failure: defined as the need for mechanical ventilation. Results Ninety-nine (68.3%) and 46 (31.7%) patients were initiated on HFNC for acute hypoxemic respiratory failure and following a planned extubation, respectively. The majority (86.9%) of patients had pneumonia as a primary diagnosis, and 85 (56.6%) patients were immunocompromised. Sixty-one (42.1%) patients required intubation (HFNC failure). Amongst patients on HFNC for acute respiratory failure, HFNC failure was associated with a lower ROX and ROX-HR index recorded at time points between 1 and 48 h. Within the first 12 h, both indices performed with the highest AUROC at 10 h as follows: 0.723 (95% CI 0.605–0.840) and 0.739 (95% CI 0.626–0.853) for the ROX and ROX-HR index respectively. A ROX-HR index of > 6.80 was significantly associated with a lower risk of HFNC failure (hazard ratio 0.301 (95% CI 0.143–0.663)) at 10 h. This association was also observed at 2, 6, 18, and 24h, even with correction for potential confounding factors. For HFNC initiated post-extubation, only the ROX-HR index remained significantly associated with HFNC failure at all recorded time points between 1 and 24 h. A ROX-HR > 8.00 at 10 h was significantly associated with a lower risk of HFNC failure (hazard ratio 0.176 (95% CI 0.051–0.604)). Conclusion While validation studies are required, the ROX-HR index appears to be a promising tool for early identification of treatment failure in patients initiated on HFNC for acute hypoxemic respiratory failure or as a preventative treatment after a planned extubation.

The current coronavirus disease 2019 (COVID-19) pandemic has not only caused global social disruptions but has also put tremendous strain on healthcare systems worldwide. With all attention and significant effort diverted to containing and managing the COVID-19 outbreak (and understandably so), essential medical services such as transplant services are likely to be affected. Closure of transplant programs in an outbreak caused by a highly transmissible novel pathogen may be inevitable owing to patient safety. Yet program closure is not without harm; patients on the transplant waitlist may die before the program reopens. By adopting a tiered approach based on outbreak disease alert levels, and having hospital guidelines based on the best available evidence, life-saving transplants can still be safely performed. We performed a lung transplant and a liver transplant successfully during the COVID-19 era. We present our guidelines and experience on managing the transplant service as well as the selection and management of donors and recipients. We also discuss clinical dilemmas in the management COVID-19 in the posttransplant recipient.

The coronavirus disease 2019 (COVID-19) has rapidly evolved into a worldwide pandemic. Preparing intensive care units (ICU) is an integral part of any pandemic response. In this review, we discuss the key principles and strategies for ICU preparedness. We also describe our initial outbreak measures and share some of the challenges faced. To achieve sustainable ICU services, we propose the need to 1) prepare and implement rapid identification and isolation protocols, and a surge in ICU bed capacity; (2) provide a sustainable workforce with a focus on infection control; (3) ensure adequate supplies to equip ICUs and protect healthcare workers; and (4) maintain quality clinical management, as well as effective communication.

Objectives:Patients with COVID-19 may present with respiratory syndromes indistinguishable from those caused by common viruses. Early isolation and containment is challenging. Although screening all patients with respiratory symptoms for COVID-19 has been recommended, the practicality of such an effort has yet to be assessed.Methods:Over a 6-week period during a SARS-CoV-2 outbreak, our institution introduced a “respiratory surveillance ward” (RSW) to segregate all patients with respiratory symptoms in designated areas, where appropriate personal protective equipment (PPE) could be utilized until SARS-CoV-2 testing was done. Patients could be transferred when SARS-CoV-2 tests were negative on 2 consecutive occasions, 24 hours apart.Results:Over the study period, 1,178 patients were admitted to the RSWs. The mean length-of-stay (LOS) was 1.89 days (SD, 1.23). Among confirmed cases of pneumonia admitted to the RSW, 5 of 310 patients (1.61%) tested positive for SARS-CoV-2. This finding was comparable to the pickup rate from our isolation ward. In total, 126 HCWs were potentially exposed to these cases; however, only 3 (2.38%) required quarantine because most used appropriate PPE. In addition, 13 inpatients overlapped with the index cases during their stay in the RSW; of these 13 exposed inpatients, 1 patient subsequently developed COVID-19 after exposure. No patient–HCW transmission was detected despite intensive surveillance.Conclusions:Our institution successfully utilized the strategy of an RSW over a 6-week period to contain a cluster of COVID-19 cases and to prevent patient–HCW transmission. However, this method was resource-intensive in terms of testing and bed capacity.

Additional file 1: Figure S1. Example of the ROX-HR index calculation. Figure S2. Proportion of patients with successful HFNC initiated after a planned extubation, based ROX-HR index at 2 hours (top graph) and 10 hours (bottom graph). Table S1. Comparison of the changes in ROX-HR and ROX index over different time points during HFNC. Table S2. Prediction of HFNC failure based on a ROX and ROX-HR cut off of < 5.00 and < 6.00 for patients initiated on HFNC for acute respiratory failure and after a planned extubation, respectively. Table S3. Cox proportional regression analysis evaluating ROX ≥ 4.88 for the likelihood of HFNC failure in patients with acute respiratory failure. Table S4. Prediction of HFNC outcomes in patients with acute respiratory failure based on ROX-HR and previously established ROX cut offs at different time points.

Objective Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. This study aims to describe the thrombotic and bleeding rates in COVID-19 patients admitted to intensive care units (ICU) in Singapore. Design Retrospective observational study involving all consecutive adult COVID-19 patients who required ICU admission between 23 January 2020 and 30 April 2020. Setting National multicenter study involving all eight public hospitals in Singapore. Patients 111 consecutive COVID-19 patients who required ICU admission were included. Measurements and Main Results Primary outcome was any venous or arterial thrombotic events occurred in ICU. Other measures included (1) the overall, venous and arterial thrombotic events throughout the hospitalisation, (2) major and minor bleeding events. The overall thrombotic rate in ICU was 11.7% (n=13), with 1.8% (n=2) venous and 9.9% (n=11) arterial events. The overall thrombotic rates throughout hospitalisation, censored at 30 April 2020, increased to 18.0% (n=20) with 6.3% (n=7) venous and 11.7% (n=13) arterial events. Major and minor bleeding rates were 14.8% (n=16) and 3.7% (n=4), respectively. Two-third of the patients received pharmacological thromboprophylaxis in ICU. Conclusions Critically ill COVID-19 patients in Singapore have lower VTE but higher arterial thrombosis rates with higher bleeding manifestations than other reported cohorts. Standard thromboprophylaxis may be sufficient to prevent thrombotic complications in patients with similar demographics. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION: The educational environment (EE) reflects the quality of a residency programme and has an association with burnout. Studying the EE allows for interventions to target specific weaknesses. We aimed to measure the EE of an internal medicine residency programme in Singapore, compare the perceptions between genders, residency grades and levels of work experience, and identify specific areas of weaknesses for intervention in hopes of reducing residency burnout rates in Singapore. METHODS: This study took place between October and December 2017. We adopted a mixed methods approach, quantitatively using the Postgraduate Hospital Educational Environment Measure (PHEEM), and qualitative exploration using semi-structured focus group discussion. RESULTS: A total of 136 (88.9%) out of 153 residents responded. Our total PHEEM scores (112.23 ± 16.71), along with the scores for all three subscales, were higher than those of institutions in previous studies. There were no differences in overall PHEEM and subscale scores between genders, residency grades or levels of work experience. However, there were differences for individual questions, which were explored in the focus group discussion. Senior residents juggling heavier workloads, responsibilities and examinations appeared to be most prone to burnout. We identified three recurring themes that contributed to a poor EE in our programme: excessive workload, poor faculty relationships and differing unmet needs. CONCLUSION: Although our programme had a good EE, there were also areas of weaknesses revealed by specific questions, possibly contributing to burnout. We hope to implement interventions to these areas and subsequently assess for longitudinal changes in EE and burnout rates.

Background Attributes of the clinical learning environment (CLE) are a measure of quality in postgraduate medical education, and assessing the CLE is a component of the New Accreditation System being introduced in Singapore by the Accreditation Council for Graduate Medical Education International. There is a dearth of published studies of CLE quality in Singapore. Objective Our study had 3 aims: (1) to measure the CLE in 1 Singaporean residency program; (2) to compare trainee perceptions by sex, training level, and experience; and (3) to identify areas for improvement. Methods Between October and December 2017, we conducted a mixed assessment of the CLE in an internal medicine program in Singapore, using the Postgraduate Hospital Educational Environment Measure (PHEEM) and qualitative exploration using a focus group. Results Of 153 IM residents, 136 (89%) provided PHEEM responses and 8 participated in the focus group. Total PHEEM scores and scores for the 3 subscales were higher than published data on the use of the PHEEM in international settings. Exploration of selected PHEEM responses via a focus group identified attributes associated with negative perceptions of the CLE: excessive workload, inadequate faculty presence in the CLE, and unmet trainee needs. It also suggested senior residents' clinical workloads, greater responsibilities, and pending examinations may contribute to their less positive perceptions of the CLE. Conclusions Our analysis using the PHEEM showed overall positive perceptions of the CLE, along with areas for improvement amenable to interventions. Our approach has relevance to an accreditation model with ongoing evaluation of the CLE.

Objectives Venovenous extracorporeal membrane oxygenation is increasingly being established as a treatment option for severe acute respiratory failure. We sought to evaluate the impact of a dedicated specialist team-based approach on patient outcomes. Design Retrospective cohort study. Setting Single-center medical ICU in an academic tertiary hospital. Patients Adult patients initiated on venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. Interventions Initiation of an extracorporeal membrane oxygenation intensivist-led multidisciplinary team; critical decisions on extracorporeal membrane oxygenation management were jointly made by a dedicated team of extracorporeal membrane oxygenation intensivists, together with the multidisciplinary team. Measurements and main results Eighty-one patients (75%) and 27 patients (35%) were initiated on venovenous extracorporeal membrane oxygenation in the preextracorporeal membrane oxygenation intensivist-led multidisciplinary team (before January 2018) and postextracorporeal membrane oxygenation intensivist-led multidisciplinary team period (after January 2018), respectively. Inhospital (14.8% vs 44.4%, p = 0.006) and ICU mortality (11.1% vs 40.7%, p = 0.005) were significantly lower in the postextracorporeal membrane oxygenation intensivist-led multidisciplinary team period. On multivariate analysis correcting for possible confounding factors (ICU severity and extracorporeal membrane oxygenation-specific mortality prediction scores, body mass index, preextracorporeal membrane oxygenation vasopressor support, preextracorporeal membrane oxygenation cardiac arrest, and days on mechanical ventilation before extracorporeal membrane oxygenation initiation), management by an extracorporeal membrane oxygenation intensivist-led multidisciplinary team remained associated with improved hospital survival (odds ratio, 5.06; 95% CI, 1.20-21.28). Patients in the postextracorporeal membrane oxygenation intensivist-led multidisciplinary team period had less nosocomial infections (18.5% vs 46.9%, p = 0.009), a shorter ICU stay (12 days [interquartile range, 6-16 d] vs 15 days [interquartile range, 10-24 d]; p = 0.049), and none suffered an intracranial hemorrhage or nonhemorrhagic stroke. Conclusions An extracorporeal membrane oxygenation intensivist-led multidisciplinary team approach is associated with improved outcomes in patients initiated on venovenous extracorporeal membrane oxygenation for severe acute respiratory failure.

INTRODUCTION Although research is widely considered to be a relevant and essential skill to resident development, the actual participation rate of residents in research remains low, and the factors associated with participation are unclear. METHODS We examined the participation rate of junior residents in research, and their attitudes and perceived barriers toward research, via an anonymised survey carried out from October to November 2013. The residents were from an established Accreditation Council for Graduate Medical Education-accredited internal medicine residency training programme in Singapore. RESULTS The overall response rate was 64.1% (82/128 residents). The most frequently cited barrier was lack of time. Only a third of the residents surveyed were actively participating in research. Those with postgraduate qualifications were more likely to be involved in research (odds ratio 4.71, p = 0.015). Among the 82 residents, 40.2% reported an interest in research as part of their career; these were mainly graduates from overseas universities or postgraduates. A belief that research is an intrinsically valuable activity distinguished residents who chose research as a career path from those who were undecided (p = 0.004). The belief that research is a means to better clinical practice also divided those who chose research from those who rejected it (p = 0.02). CONCLUSION Our findings suggest that specific beliefs determine the level of research activity and career interest among residents. Novel strategies may be incorporated in training programmes to improve the interest and participation of residents in research, and to facilitate the development of academic clinicians.

Transbronchial needle aspiration (TBNA) is a bronchoscopic technique that provides access to masses within the mediastinum. It is operator dependent, and factors such as needle type, lymph node site, and endobronchial ultrasosonography (EBUS) have been implicated as having an impact on its accuracy. This study aimed to develop a strategy for TBNA and specimen preparation techniques as the first step toward improving TBNA yield, and to determine whether EBUS can augment its application. Intervention included standardizing the use of the histology needle and the direct smear method. As competency improved, radial probe (RP) and linear EBUS were incorporated into TBNA. The study assessed 35 conventional TBNA procedures before and 45 of these procedures after intervention as well as 45 RP-EBUS and 50 linear EBUS-guided TBNA procedures. Frequently sampled lymph node stations were 7, 4R, and 4L in the American Thoracic Society classification. The preintervention conventional TBNA yield was 43%, which improved to 82% after intervention. Although EBUS did not have an impact on TBNA yield (p = 0.44) compared with the intervention (p = 0.001), EBUS was useful for lymph nodes smaller than 2 cm (p

Intensive Care Unit (ICU) patients often require urgent, high-risk diagnostic and therapeutic procedures. However, they are particularly vulnerable to procedural complications due to the severity and instability of their illnesses. We discuss the complications associated with bronchoscopy, percutaneous dilatational tracheostomy, pleural interventions for example thoracentesis and chest tube placement, central venous catheterization and pulmonary artery catheterization. Invasive procedures are frequently performed in critically ill patients. It is important for the operator to be familiar with the specific complications of each procedure, as well as steps to take in order to enhance safety and reduce adverse events. High standards of training and credentialing are crucial to ensure that the ICU physicians are proficient in performing these procedures.

Introduction: Haemodynamic monitoring is an essential element in the management of critically ill patients in the intensive care unit (ICU). However, there have been increasing concerns about the clinical utility and safety profile of the invasive pulmonary artery catheter (PAC). Oesophageal Doppler (ED) monitoring has emerged recently as a safer and less invasive tool which can be used by the intensivist to estimate cardiac output in the critically ill patient. Validation studies have thus far only been performed in surgical patients perioperatively and in mixed surgical/medical ICU patients. Currently, minimal data are available in any sizeable Asian population or in patients with severe sepsis. The assumption that these normograms and data hold true for our local medical ICU patients may not be valid due to differences in body habitus. Materials and Methods: Our primary aim is to validate the oesophageal Doppler as a reliable measure of cardiac index, systemic vascular resistance (SVR) and preload in our local Asian population of patients with severe sepsis and septic shock in the medical ICU. This was a prospective pilot study on 12 consecutive mechanically ventilated patients in our medical ICU with the diagnosis of septic shock as defined by SCCM/ESICM/ACCP/ATS/SIS International Sepsis definitions Conference – Critical Care Medicine 2003 and required PAC haemodynamic monitoring as indicated by Medical Intensive Care Unit attending. Results: Ninety-seven paired cardiac output measurements were made. Cardiac output ranged from 2.87 to 11.0 L/ min (calculated cardiac index ranging from 1.73 to 6.36 L/min/m2) when measured using the PAC with thermodilution technique and from 2.0 to 12.1 L/min (calculated cardiac index of 1.2 to 7.2 L/min/m2) using the trans-oesophageal Doppler. There was moderately good correlation between CIpac and CIed (correlation coefficient, r = 0.762 with PCA = 58%). The mean bias was 0.26 L/min/m2 (P

With the increasing threat of pandemic influenza and catastrophic bioterrorism, it is important for intensive care providers to be prepared to meet the challenge of large-scale airborne epidemics causing mass casualty respiratory failure. The severe acute respiratory syndrome outbreak exposed the vulnerability of health care workers and highlighted the importance of establishing stringent infection control and crisis management protocols. Patients who have acute lung injury and acute respiratory distress syndrome who require mechanical ventilation should receive a lung protective, low tidal volume strategy. Controversy remains regarding the use of high-frequency oscillatory ventilation and noninvasive positive pressure ventilation. Standard, contact, and airborne precautions should be instituted in intensive care units, with special care taken when aerosol-generating procedures are performed.