Epidemiology, Management, and Outcomes of Sepsis in ICUs among Countries of Differing National Wealth across Asia.

Rationale: Directly comparative data on sepsis epidemiology and sepsis bundle implementation in countries of differing national wealth remain sparse. Objectives: To evaluate across countries/regions of differing income status in Asia 1) the prevalence, causes, and outcomes of sepsis as a reason for ICU admission and 2) sepsis bundle (antibiotic administration, blood culture, and lactate measurement) compliance and its association with hospital mortality. Methods: A prospective point prevalence study was conducted among 386 adult ICUs from 22 Asian countries/regions. Adult ICU participants admitted for sepsis on four separate days (representing the seasons of 2019) were recruited. Measurements and Main Results: The overall prevalence of sepsis in ICUs was 22.4% (20.9%, 24.5%, and 21.3% in low-income countries/regions [LICs]/lower middle-income countries/regions [LMICs], upper middle-income countries/regions, and high-income countries/regions [HICs], respectively; P < 0.001). Patients were younger and had lower severity of illness in LICs/LMICs. Hospital mortality was 32.6% and marginally significantly higher in LICs/LMICs than HICs on multivariable generalized mixed model analysis (adjusted odds ratio, 1.84; 95% confidence interval, 1.00-3.37; P = 0.049). Sepsis bundle compliance was 21.5% at 1 hour (26.0%, 22.1%, and 16.2% in LICs/LMICs, upper middle-income countries/regions, and HICs, respectively; P < 0.001) and 36.6% at 3 hours (39.3%, 32.8%, and 38.5%, respectively; P = 0.001). Delaying antibiotic administration beyond 3 hours was the only element independently associated with increased mortality (adjusted odds ratio, 2.53; 95% confidence interval, 2.07-3.08; P < 0.001). Conclusions: Sepsis is a common cause of admission to Asian ICUs. Mortality remains high and is higher in LICs/LMICs after controlling for confounders. Sepsis bundle compliance remains low. Delaying antibiotic administration beyond 3 hours from diagnosis is associated with increased mortality. Clinical trial registered with www.ctri.nic.in (CTRI/2019/01/016898).

The story of critical care in Asia: a narrative review.

BACKGROUND: Asia has more critically ill people than any other part of our planet. The aim of this article is to review the development of critical care as a specialty, critical care societies and education and research, the epidemiology of critical illness as well as epidemics and pandemics, accessibility and cost and quality of critical care, culture and end-of-life care, and future directions for critical care in Asia. MAIN BODY: Although the first Asian intensive care units (ICUs) surfaced in the 1960s and the 1970s and specialisation started in the 1990s, multiple challenges still exist, including the lack of intensivists, critical care nurses, and respiratory therapists in many countries. This is aggravated by the brain drain of skilled ICU staff to high-income countries. Critical care societies have been integral to the development of the discipline and have increasingly contributed to critical care education, although critical care research is only just starting to take off through collaboration across groups. Sepsis, increasingly aggravated by multidrug resistance, contributes to a significant burden of critical illness, while epidemics and pandemics continue to haunt the continent intermittently. In particular, the coronavirus disease 2019 (COVID-19) has highlighted the central role of critical care in pandemic response. Accessibility to critical care is affected by lack of ICU beds and high costs, and quality of critical care is affected by limited capability for investigations and treatment in low- and middle-income countries. Meanwhile, there are clear cultural differences across countries, with considerable variations in end-of-life care. Demand for critical care will rise across the continent due to ageing populations and rising comorbidity burdens. Even as countries respond by increasing critical care capacity, the critical care community must continue to focus on training for ICU healthcare workers, processes anchored on evidence-based medicine, technology guided by feasibility and impact, research applicable to Asian and local settings, and rallying of governments for support for the specialty. CONCLUSIONS: Critical care in Asia has progressed through the years, but multiple challenges remain. These challenges should be addressed through a collaborative approach across disciplines, ICUs, hospitals, societies, governments, and countries.

Risk of dispersion or aerosol generation and infection transmission with nasopharyngeal and oropharyngeal swabs for detection of COVID-19: a systematic review.

OBJECTIVES: SARS-CoV-2-related disease, referred to as COVID-19, has emerged as a global pandemic since December 2019. While there is growing recognition regarding possible airborne transmission, particularly in the setting of aerosol-generating procedures and treatments, whether nasopharyngeal and oropharyngeal swabs for SARS-CoV-2 generate aerosols remains unclear. DESIGN: Systematic review. DATA SOURCES: We searched Ovid MEDLINE and EMBASE up to 3 November 2020. We also searched the China National Knowledge Infrastructure, Chinese Medical Journal Network, medRxiv and ClinicalTrials.gov up to 29 March 2020. ELIGIBILITY CRITERIA: All comparative and non-comparative studies that evaluated dispersion or aerosolisation of viable airborne organisms, or transmission of infection associated with nasopharyngeal or oropharyngeal swab testing. RESULTS: Of 7702 citations, only one study was deemed eligible. Using a dedicated sampling room with negative pressure isolation room, personal protective equipment including N95 or higher masks, strict sterilisation protocols, structured training with standardised collection methods and a structured collection and delivery system, a tertiary care hospital proved a 0% healthcare worker infection rate among eight nurses conducting over 11 000 nasopharyngeal swabs. No studies examining transmissibility with other safety protocols, nor any studies quantifying the risk of aerosol generation with nasopharyngeal or oropharyngeal swabs for detection of SARS-CoV-2, were identified. CONCLUSIONS: There is limited to no published data regarding aerosol generation and risk of transmission with nasopharyngeal and oropharyngeal swabs for the detection of SARS-CoV-2. Field experiments to quantify this risk are warranted. Vigilance in adhering to current standards for infection control is suggested.

How the COVID-19 pandemic will change the future of critical care.

Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.

Mechanical Ventilation Discontinuation Practices in Asia: A Multinational Survey.

Rationale: There are limited data on mechanical discontinuation practices in Asia. Objectives: To document self-reported mechanical discontinuation practices and determine whether there is clinical equipoise regarding protocolized weaning among Asian Intensive Care specialists. Methods: A survey using a validated questionnaire, distributed using a snowball method to Asian Intensive Care specialists. Results: Of the 2,967 invited specialists from 20 territories, 2,074 (69.9%) took part. The majority of respondents (60.5%) were from China. Of the respondents, 42% worked in intensive care units (ICUs) where respiratory therapists were present; 78.9% used a spontaneous breathing trial as the initial weaning step; 44.3% frequently/always used pressure support (PS) alone, 53.4% intermittent spontaneous breathing trials with PS in between, and 19.8% synchronized intermittent mandatory ventilation with PS as a weaning mode. Of the respondents, 56.3% routinely stopped feeds before extubation, 71.5% generally followed a sedation protocol or guideline, and 61.8% worked in an ICU with a weaning protocol. Of these, 78.2% frequently always followed the protocol. A multivariate analysis involving a modified Poisson regression analysis showed that working in an ICU with a weaning protocol and frequently/always following it was positively associated with an upper-middle-income territory, a university-affiliated hospital, or in an ICU that employed respiratory therapists; and negatively with a low-income or lower-middle-income territory or a public hospital. There was no significant association with "in-house" intensivist at night, multidisciplinary ICU, closed ICU, or nurse-patient ratio. There was heterogeneity in agreement/disagreement with the statement, "evidence clearly supports protocolized weaning over nonprotocolized weaning." Conclusions: A substantial minority of Asian Intensive Care specialists do not wean patients in accordance with the best available evidence or current guidelines. There is clinical equipoise regarding the benefit of protocolized weaning.

Intensive care management of coronavirus disease 2019 (COVID-19): challenges and recommendations.

As coronavirus disease 2019 (COVID-19) spreads across the world, the intensive care unit (ICU) community must prepare for the challenges associated with this pandemic. Streamlining of workflows for rapid diagnosis and isolation, clinical management, and infection prevention will matter not only to patients with COVID-19, but also to health-care workers and other patients who are at risk from nosocomial transmission. Management of acute respiratory failure and haemodynamics is key. ICU practitioners, hospital administrators, governments, and policy makers must prepare for a substantial increase in critical care bed capacity, with a focus not just on infrastructure and supplies, but also on staff management. Critical care triage to allow the rationing of scarce ICU resources might be needed. Researchers must address unanswered questions, including the role of repurposed and experimental therapies. Collaboration at the local, regional, national, and international level offers the best chance of survival for the critically ill.

Critically ill patients with COVID-19 in Hong Kong: a multicentre retrospective observational cohort study

Objective: To report the first eight cases of critically ill patients with coronavirus disease 2019 (COVID-19) in Hong Kong, describing the treatments and supportive care they received and their 28-day outcomes. Design: Multicentre retrospective observational cohort study. Setting: Three multidisciplinary intensive care units (ICUs) in Hong Kong. Participants: All adult critically ill patients with confirmed COVID-19 admitted to ICUs in Hong Kong between 22 January and 11 February 2020. Main outcome measure: 28-day mortality. Results: Eight out of 49 patients with COVID-19 (16%) were admitted to Hong Kong ICUs during the study period. The median age was 64.5 years (range, 42­70) with a median admission Sequential Organ Failure Assessment (SOFA) score of 6 (IQR, 4­7). Six patients (75%) required mechanical ventilation, six patients (75%) required vasopressors and two (25%) required renal replacement therapy. None of the patients required prone ventilation, nitric oxide or extracorporeal membrane oxygenation. The median times to shock reversal and extubation were 9 and 11 days respectively. At 28 days, one patient (12%) had died and the remaining seven (88%) all survived to ICU discharge. Only one of the survivors (14%) still required oxygen at 28 days. Conclusion: Critically ill patients with COVID-19 often require a moderate duration of mechanical ventilation and vasopressor support. Most of these patients recover and survive to ICU discharge with supportive care using lung protective ventilation strategies, avoiding excess fluids, screening and treating bacterial co-infection, and timely intubation. Lower rather than upper respiratory tract viral burden correlates with clinical severity of illness.

In-vitro adsorption and sieving coefficient of ticarcillin-clavulanate during continuous haemofiltration.

There are very limited data on ticarcillin-clavulanate elimination by haemofiltration. We measured in vitro ticarcillin-clavulanate adsorption to polyacrylonitrile (PAN) filters and the sieving coefficient using a well-described bench model of haemofiltration. The dose of ticarcillin-clavulanate was 60/2 mg or 180/3 mg, and 0 or 12 g albumin was added to the 1 L of circulating blood-crystalloid mixture to produce four different experimental conditions. The experiment was repeated four times under each condition. Median (interquartile range [IQR] ) ticarcillin adsorption varied from 28 (27-30) mg to 85 (78-90) mg. Adsorption was increased when the dose of ticarcillin was higher (P<0.001), but was not affected by the addition of albumin. Median (IQR) adsorption of clavulanate ranged from 0.67 (0.55-0.75) mg to 1.8 (0.33-3.5) mg and was neither dose dependent (P = 0.505) nor significantly affected by the addition of albumin. Median (IQR) ticarcillin sieving coefficient ranged from 0.73 (0.67-0.75) to 0.99 (0.97-1.03). It was significantly higher with a higher dose of ticarcillin (P = 0.021) and without addition of albumin (P = 0.015). Median (IQR) clavulanate sieving coefficient ranged from 1.03 (1.00-2.24) to 2.0 (1.98-2.47). Clavulanate sieving coefficient was not significantly affected by dose or the addition of albumin. These data indicate that significant adsorption of both ticarcillin and clavulanate occurs in vitro; however, this requires confirmation by clinical pharmacokinetic studies. The sieving coefficient data may help guide appropriate dosing of critically ill patients receiving haemofiltration until more extensive clinical pharmacokinetic data are available.

Exploring the scope of communication content of mechanically ventilated patients.

PURPOSE: Ineffective communication during mechanical ventilation (MV) and critical illness is distressing to many patients. This study aimed to describe the scope of communication content of ventilated critically ill patients. MATERIALS AND METHODS: We performed a prospective qualitative interview study in a multidisciplinary intensive care unit. Ten alert, orientated adult patients who previously underwent MV for at least 24h and were able to speak at the time of interview were recruited. Semi-structured interviews with stimulated recall technique were conducted. A descriptive thematic analysis was performed of the patient-generated content using a free coding technique, where recurrent themes and subthemes were noted, coded and analyzed. RESULTS: Patients' communication content included medical discussions with clinicians; communication with family to provide advice or comfort, make requests and plans, express feelings and convey personal perspectives on medical care; and expression of their own psychoemotional needs. CONCLUSIONS: The scope of communication content of ventilated ICU patients was broad, extending far beyond task-focused subject matter. Content ranged from conveying symptom-related messages to active participation in medical discussions, to conversing with family about a range of complex multi-dimensional issues, to sharing their own psychoemotional experiences. These patient-centered needs should be recognized and addressed in communication strategies.

Is inhaled prophylactic heparin useful for prevention and Management of Pneumonia in ventilated ICU patients?: The IPHIVAP investigators of the Australian and New Zealand Intensive Care Society Clinical Trials Group.

PURPOSE: To determine whether prophylactic inhaled heparin is effective for the prevention and treatment of pneumonia patients receiving mechanical ventilation (MV) in the intensive care unit. METHODS: A phase 2, double blind randomized controlled trial stratified for study center and patient type (non-operative, post-operative) was conducted in three university-affiliated intensive care units. Patients aged ≥18years and requiring invasive MV for more than 48hours were randomized to usual care, nebulization of unfractionated sodium heparin (5000 units in 2mL) or placebo nebulization with 0.9% sodium chloride (2mL) four times daily with the main outcome measures of the development of ventilator associated pneumonia (VAP), ventilator associated complication (VAC) and sequential organ failure assessment scores in patients with pneumonia on admission or who developed VAP. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12612000038897. RESULTS: Two hundred and fourteen patients were enrolled (72 usual care, 71 inhaled sodium heparin, 71 inhaled sodium chloride). There were no differences between treatment groups in terms of the development of VAP, using either Klompas criteria (6-7%, P=1.00) or clinical diagnosis (24-26%, P=0.85). There was no difference in the clinical consistency (P=0.70), number (P=0.28) or the total volume of secretions per day (P=.54). The presence of blood in secretions was significantly less in the usual care group (P=0.005). CONCLUSION: Nebulized heparin cannot be recommended for prophylaxis against VAP or to hasten recovery from pneumonia in patients receiving MV.

To increase or decrease dosage of antimicrobials in septic patients during continuous renal replacement therapy: the eternal doubt.

Critical illness, acute renal failure and continuous renal replacement therapy (CRRT) are associated with changes in pharmacokinetics. Initial antibiotic dose should be based on published volume of distribution and generally be at least the standard dose, as volume of distribution is usually unchanged or increased. Subsequent doses should be based on total clearance. Total clearance varies with the CRRT clearance which mainly depends on effluent flow rate, sieving coefficient/saturation coefficient. As antibiotic clearance by healthy kidneys is usually higher than clearance by CRRT, except for colistin, subsequent doses should generally be lower than given to patients without renal dysfunction. In the future therapeutic drug monitoring, together with sophisticated pharmacokinetic models taking into account the pharmacokinetic variability, may enable more appropriate individualized dosing.

Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study.

PURPOSE: Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients. METHODS: The Acute Kidney Injury-Epidemiologic Prospective Investigation (AKI-EPI) study was an international cross-sectional study performed in 97 centers on patients during the first week of ICU admission. We measured AKI by Kidney Disease: Improving Global Outcomes (KDIGO) criteria, and outcomes at hospital discharge. RESULTS: A total of 1032 ICU patients out of 1802 [57.3%; 95% confidence interval (CI) 55.0-59.6] had AKI. Increasing AKI severity was associated with hospital mortality when adjusted for other variables; odds ratio of stage 1 = 1.679 (95% CI 0.890-3.169; p = 0.109), stage 2 = 2.945 (95% CI 1.382-6.276; p = 0.005), and stage 3 = 6.884 (95% CI 3.876-12.228; p < 0.001). Risk-adjusted rates of AKI and mortality were similar across the world. Patients developing AKI had worse kidney function at hospital discharge with estimated glomerular filtration rate less than 60 mL/min/1.73 m(2) in 47.7% (95% CI 43.6-51.7) versus 14.8% (95% CI 11.9-18.2) in those without AKI, p < 0.001. CONCLUSIONS: This is the first multinational cross-sectional study on the epidemiology of AKI in ICU patients using the complete KDIGO criteria. We found that AKI occurred in more than half of ICU patients. Increasing AKI severity was associated with increased mortality, and AKI patients had worse renal function at the time of hospital discharge. Adjusted risks for AKI and mortality were similar across different continents and regions.

A randomized controlled trial of adaptive support ventilation mode to wean patients after fast-track cardiac valvular surgery.

BACKGROUND: Adaptive support ventilation can speed weaning after coronary artery surgery compared with protocolized weaning using other modes. There are no data to support this mode of weaning after cardiac valvular surgery. Furthermore, control group weaning times have been long, suggesting that the results may reflect control group protocols that delay weaning rather than a real advantage of adaptive support ventilation. METHODS: Randomized (computer-generated sequence and sealed opaque envelopes), parallel-arm, unblinded trial of adaptive support ventilation versus physician-directed weaning after adult fast-track cardiac valvular surgery. The primary outcome was duration of mechanical ventilation. Patients aged 18 to 80 yr without significant renal, liver, or lung disease or severe impairment of left ventricular function undergoing uncomplicated elective valve surgery were eligible. Care was standardized, except postoperative ventilation. In the adaptive support ventilation group, target minute ventilation and inspired oxygen concentration were adjusted according to blood gases. A spontaneous breathing trial was carried out when the total inspiratory pressure of 15 cm H2O or less with positive end-expiratory pressure of 5 cm H2O. In the control group, the duty physician made all ventilatory decisions. RESULTS: Median duration of ventilation was statistically significantly shorter (P = 0.013) in the adaptive support ventilation group (205 [141 to 295] min, n = 30) than that in controls (342 [214 to 491] min, n = 31). Manual ventilator changes and alarms were less common in the adaptive support ventilation group, and arterial blood gas estimations were more common. CONCLUSION: Adaptive support ventilation reduces ventilation time by more than 2 h in patients who have undergone fast-track cardiac valvular surgery while reducing the number of manual ventilator changes and alarms.

Resource-poor settings: infrastructure and capacity building: care of the critically ill and injured during pandemics and disasters: CHEST consensus statement.

BACKGROUND: Planning for mass critical care (MCC) in resource-poor or constrained settings has been largely ignored, despite their large populations that are prone to suffer disproportionately from natural disasters. Addressing MCC in these settings has the potential to help vast numbers of people and also to inform planning for better-resourced areas. METHODS: The Resource-Poor Settings panel developed five key question domains; defining the term resource poor and using the traditional phases of disaster (mitigation/preparedness/response/recovery), literature searches were conducted to identify evidence on which to answer the key questions in these areas. Given a lack of data upon which to develop evidence-based recommendations, expert-opinion suggestions were developed, and consensus was achieved using a modified Delphi process. RESULTS: The five key questions were then separated as follows: definition, infrastructure and capacity building, resources, response, and reconstitution/recovery of host nation critical care capabilities and research. Addressing these questions led the panel to offer 33 suggestions. Because of the large number of suggestions, the results have been separated into two sections: part 1, Infrastructure/Capacity in this article, and part 2, Response/Recovery/Research in the accompanying article. CONCLUSIONS: Lack of, or presence of, rudimentary ICU resources and limited capacity to enhance services further challenge resource-poor and constrained settings. Hence, capacity building entails preventative strategies and strengthening of primary health services. Assistance from other countries and organizations is needed to mount a surge response. Moreover, planning should include when to disengage and how the host nation can provide capacity beyond the mass casualty care event.

Resource-poor settings: response, recovery, and research: care of the critically ill and injured during pandemics and disasters: CHEST consensus statement.

BACKGROUND: Planning for mass critical care in resource-poor and constrained settings has been largely ignored, despite large, densely crowded populations who are prone to suffer disproportionately from natural disasters. As a result, disaster response has been suboptimal and in many instances hampered by lack of planning, education and training, information, and communication. METHODS: The Resource-Poor Settings panel developed five key question domains; defining the term resource poor and using the traditional phases of the disaster cycle (mitigation/preparedness/response/recovery). Literature searches were conducted to identify evidence to answer the key questions in these areas. Given a lack of data on which to develop evidence-based recommendations, expert-opinion suggestions were developed, and consensus was achieved using a modified Delphi process. RESULTS: The five key questions were as follows: definition, capacity building and mitigation, what resources can we bring to bear to assist/surge, response, and reconstitution and recovery of host nation critical care capabilities. Addressing these led the panel to offer 33 suggestions. Because of the large number of suggestions, the results have been separated into two sections: part I, Infrastructure/Capacity in the accompanying article, and part II, Response/Recovery/Research in this article. CONCLUSIONS: A lack of rudimentary ICU resources and capacity to enhance services plagues resource-poor or constrained settings. Capacity building therefore entails preventative strategies and strengthening of primary health services. Assistance from other countries and organizations is often needed to mount a surge response. Moreover, the disengagement of these responding groups and host country recovery require active planning. Future improvements in all phases require active research activities.

Triage: care of the critically ill and injured during pandemics and disasters: CHEST consensus statement.

BACKGROUND: Pandemics and disasters can result in large numbers of critically ill or injured patients who may overwhelm available resources despite implementing surge-response strategies. If this occurs, critical care triage, which includes both prioritizing patients for care and rationing scarce resources, will be required. The suggestions in this chapter are important for all who are involved in large-scale pandemics or disasters with multiple critically ill or injured patients, including front-line clinicians, hospital administrators, and public health or government officials. METHODS: The Triage topic panel reviewed previous task force suggestions and the literature to identify 17 key questions for which specific literature searches were then conducted to identify studies upon which evidence-based recommendations could be made. No studies of sufficient quality were identified. Therefore, the panel developed expert opinion-based suggestions using a modified Delphi process. Suggestions from the previous task force that were not being updated were also included for validation by the expert panel. RESULTS: The suggestions from the task force outline the key principles upon which critical care triage should be based as well as a path for the development of the plans, processes, and infrastructure required. This article provides 11 suggestions regarding the principles upon which critical care triage should be based and policies to guide critical care triage. CONCLUSIONS: Ethical and efficient critical care triage is a complex process that requires significant planning and preparation. At present, the prognostic tools required to produce an effective decision support system (triage protocol) as well as the infrastructure, processes, legal protections, and training are largely lacking in most jurisdictions. Therefore, critical care triage should be a last resort after mass critical care surge strategies.