A New Global Definition of Acute Respiratory Distress Syndrome.

Background: Since publication of the 2012 Berlin definition of acute respiratory distress syndrome (ARDS), several developments have supported the need for an expansion of the definition, including the use of high-flow nasal oxygen, the expansion of the use of pulse oximetry in place of arterial blood gases, the use of ultrasound for chest imaging, and the need for applicability in resource-limited settings. Methods: A consensus conference of 32 critical care ARDS experts was convened, had six virtual meetings (June 2021 to March 2022), and subsequently obtained input from members of several critical care societies. The goal was to develop a definition that would 1) identify patients with the currently accepted conceptual framework for ARDS, 2) facilitate rapid ARDS diagnosis for clinical care and research, 3) be applicable in resource-limited settings, 4) be useful for testing specific therapies, and 5) be practical for communication to patients and caregivers. Results: The committee made four main recommendations: 1) include high-flow nasal oxygen with a minimum flow rate of ⩾30 L/min; 2) use PaO2:FiO2 ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry SpO2:FiO2 ⩽ 315 (if oxygen saturation as measured by pulse oximetry is ⩽97%) to identify hypoxemia; 3) retain bilateral opacities for imaging criteria but add ultrasound as an imaging modality, especially in resource-limited areas; and 4) in resource-limited settings, do not require positive end-expiratory pressure, oxygen flow rate, or specific respiratory support devices. Conclusions: We propose a new global definition of ARDS that builds on the Berlin definition. The recommendations also identify areas for future research, including the need for prospective assessments of the feasibility, reliability, and prognostic validity of the proposed global definition.

Promises and challenges of personalized medicine to guide ARDS therapy.

Identifying new effective treatments for the acute respiratory distress syndrome (ARDS), including COVID-19 ARDS, remains a challenge. The field of ARDS investigation is moving increasingly toward innovative approaches such as the personalization of therapy to biological and clinical sub-phenotypes. Additionally, there is growing recognition of the importance of the global context to identify effective ARDS treatments. This review highlights emerging opportunities and continued challenges for personalizing therapy for ARDS, from identifying treatable traits to innovative clinical trial design and recognition of patient-level factors as the field of critical care investigation moves forward into the twenty-first century.

Critical care outcomes in resource-limited settings.

PURPOSE OF REVIEW: The burden of critical illness in low-income and middle-income countries (LMICs) is substantial. A better understanding of critical care outcomes is essential for improving critical care delivery in resource-limited settings. In this review, we provide an overview of recent literature reporting on critical care outcomes in LMICs. We discuss several barriers and potential solutions for a better understanding of critical care outcomes in LMICs. RECENT FINDINGS: Epidemiologic studies show higher in-hospital mortality rates for critically ill patients in LMICs as compared with patients in high-income countries (HICs). Recent findings suggest that critical care interventions that are effective in HICs may not be effective and may even be harmful in LMICs. Little data on long-term and morbidity outcomes exist. Better outcomes measurement is beginning to emerge in LMICs through decision support tools that report process outcome measures, studies employing mobile health technologies with community health workers and the development of context-specific severity of illness scores. SUMMARY: Outcomes from HICs cannot be reliably extrapolated to LMICs, so it is important to study outcomes for critically ill patients in LMICs. Specific challenges to achieving meaningful outcomes studies in LMICs include defining the critically ill population when few ICU beds exist, the resource-intensiveness of long-term follow-up, and the need for reliable severity of illness scores to interpret outcomes. Although much work remains to be done, examples of studies overcoming these challenges are beginning to emerge.

Diagnosing acute respiratory distress syndrome in resource limited settings: the Kigali modification of the Berlin definition.

PURPOSE OF REVIEW: The acute respiratory distress syndrome (ARDS) was re-defined by a panel of experts in Berlin in 2012. Although the Berlin criteria improved upon the validity and reliability of the definition, it did not make diagnosis of ARDS in resource limited settings possible. Mechanical ventilation, arterial blood gas measurements, and chest radiographs are not feasible in many regions of the world. In 2014, we proposed and applied the Kigali modification of the Berlin definition in a hospital in Rwanda. This review synthesizes literature from the last 18 months relevant to the Kigali modification. RECENT FINDINGS: In the last 18 months, the need for a universally applicable ARDS definition was reinforced by advances in supportive care that can be implemented in resource poor settings. Research demonstrating the variable impact of positive end expiratory pressure on hypoxemia, the validity of using pulse oximetry rather than arterial blood gas to categorize hypoxemia, and the accuracy of lung ultrasound support the use of the Kigali modification of the Berlin definition. SUMMARY: Studies directly comparing the Berlin definition to the Kigali modification are needed. Ongoing clinical research on ARDS needs to include low-income countries.

Hospital Incidence and Outcomes of the Acute Respiratory Distress Syndrome Using the Kigali Modification of the Berlin Definition.

RATIONALE: Estimates of the incidence of the acute respiratory distress syndrome (ARDS) in high- and middle-income countries vary from 10.1 to 86.2 per 100,000 person-years in the general population. The epidemiology of ARDS has not been reported for a low-income country at the level of the population, hospital, or intensive care unit (ICU). The Berlin definition may not allow identification of ARDS in resource-constrained settings. OBJECTIVES: To estimate the incidence and outcomes of ARDS at a Rwandan referral hospital using the Kigali modification of the Berlin definition: without requirement for positive end-expiratory pressure, hypoxia cutoff of SpO2/FiO2 less than or equal to 315, and bilateral opacities on lung ultrasound or chest radiograph. METHODS: We screened every adult patient for hypoxia at a public referral hospital in Rwanda for 6 weeks. For every patient with hypoxia, we collected data on demographics and ARDS risk factors, performed lung ultrasonography, and evaluated chest radiography when available. MEASUREMENTS AND MAIN RESULTS: Forty-two (4.0%) of 1,046 hospital admissions met criteria for ARDS. Using various prespecified cutoffs for the SpO2/FiO2 ratio resulted in almost identical hospital incidence values. Median age for patients with ARDS was 37 years, and infection was the most common risk factor (44.1%). Only 30.9% of patients with ARDS were admitted to an ICU, and hospital mortality was 50.0%. Using traditional Berlin criteria, no patients would have met criteria for ARDS. CONCLUSIONS: ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings.

Association of clinical prediction scores with hospital mortality in an adult medical and surgical intensive care unit in Kenya.

Importance: Mortality prediction among critically ill patients in resource limited settings is difficult. Identifying the best mortality prediction tool is important for counseling patients and families, benchmarking quality improvement efforts, and defining severity of illness for clinical research studies. Objective: Compare predictive capacity of the Modified Early Warning Score (MEWS), Universal Vital Assessment (UVA), Tropical Intensive Care Score (TropICS), Rwanda Mortality Probability Model (R-MPM), and quick Sequential Organ Failure Assessment (qSOFA) for hospital mortality among adults admitted to a medical-surgical intensive care unit (ICU) in rural Kenya. We performed a pre-planned subgroup analysis among ICU patients with suspected infection. Design setting and participants: Prospective single-center cohort study at a tertiary care, academic hospital in Kenya. All adults 18 years and older admitted to the ICU January 2018-June 2019 were included. Main outcomes and measures: The primary outcome was association of clinical prediction tool score with hospital mortality, as defined by area under the receiver operating characteristic curve (AUROC). Demographic, physiologic, laboratory, therapeutic, and mortality data were collected. 338 patients were included, none were excluded. Median age was 42 years (IQR 33-62) and 61% (n = 207) were male. Fifty-nine percent (n = 199) required mechanical ventilation and 35% (n = 118) received vasopressors upon ICU admission. Overall hospital mortality was 31% (n = 104). 323 patients had all component variables recorded for R-MPM, 261 for MEWS, and 253 for UVA. The AUROC was highest for MEWS (0.76), followed by R-MPM (0.75), qSOFA (0.70), and UVA (0.69) (p < 0.001). Predictive capacity was similar among patients with suspected infection. Conclusion and relevance: All tools had acceptable predictive capacity for hospital mortality, with variable observed availability of the component data. R-MPM and MEWS had high rates of variable availability as well as good AUROC, suggesting these tools may prove useful in low resource ICUs.

Oxygen as an Essential Medicine.

Supplemental oxygen is an essential medication in critical care. The optimal oxygen dose delivery system remains unclear, however. The "dose" and "delivery" of oxygen carry significant importance for resource-limited settings, such as low- and middle-income countries (LMICs). Regrettably, LMICS often experience significant inequities in oxygen supply and demand, with major impacts on preventable mortality. These inequities have become particularly prominent during the global COVID-19 pandemic, highlighting the need for additional investment and research into the best methods to utilize supplemental oxygen and ensure stable access to medical oxygen.

Assessment of a Crisis Standards of Care Scoring System for Resource Prioritization and Estimated Excess Mortality by Race, Ethnicity, and Socially Vulnerable Area During a Regional Surge in COVID-19.

Importance: Crisis standards of care (CSOC) scores designed to allocate scarce resources during the COVID-19 pandemic could exacerbate racial disparities in health care. Objective: To analyze the association of a CSOC scoring system with resource prioritization and estimated excess mortality by race, ethnicity, and residence in a socially vulnerable area. Design, Setting, and Participants: This retrospective cohort analysis included adult patients in the intensive care unit during a regional COVID-19 surge from April 13 to May 22, 2020, at 6 hospitals in a health care network in greater Boston, Massachusetts. Participants were scored by acute severity of illness using the Sequential Organ Failure Assessment score and chronic severity of illness using comorbidity and life expectancy scores, and only participants with complete scores were included. The score was ordinal, with cutoff points suggested by the Massachusetts guidelines. Exposures: Race, ethnicity, Social Vulnerability Index. Main Outcomes and Measures: The primary outcome was proportion of patients in the lowest priority score category stratified by self-reported race. Secondary outcomes were discrimination and calibration of the score overall and by race, ethnicity, and neighborhood Social Vulnerability Index. Projected excess deaths were modeled by race, using the priority scoring system and a random lottery. Results: Of 608 patients in the intensive care unit during the study period, 498 had complete data and were included in the analysis; this population had a median (IQR) age of 67 (56-75) years, 191 (38.4%) female participants, 79 (15.9%) Black participants, and 225 patients (45.7%) with COVID-19. The area under the receiver operating characteristic curve for the priority score was 0.79 and was similar across racial groups. Black patients were more likely than others to be in the lowest priority group (12 [15.2%] vs 34 [8.1%]; P = .046). In an exploratory simulation model using the score for ventilator allocation, with only those in the highest priority group receiving ventilators, there were 43.9% excess deaths among Black patients (18 of 41 patients) and 28.6% (58 of 203 patients among all others (P = .05); when the highest and intermediate priority groups received ventilators, there were 4.9% (2 of 41 patients) excess deaths among Black patients and 3.0% (6 of 203) among all others (P = .53). A random lottery resulted in more excess deaths than the score. Conclusions and Relevance: In this study, a CSOC priority score resulted in lower prioritization of Black patients to receive scarce resources. A model using a random lottery resulted in more estimated excess deaths overall without improving equity by race. CSOC policies must be evaluated for their potential association with racial disparities in health care.

Critical care in resource-poor settings: lessons learned and future directions.

CONTEXT: Critical care faces the same challenges as other aspects of healthcare in the developing world. However, critical care faces an additional challenge in that it has often been deemed too costly or complicated for resource-poor settings. This lack of prioritization is not justified. Hospital care for the sickest patients affects overall mortality, and public health interventions depend on community confidence in healthcare to ensure participation and adherence. Some of the most effective critical care interventions, including rapid fluid resuscitation, early antibiotics, and patient monitoring, are relatively inexpensive. Although cost-effectiveness studies on critical care in resource-poor settings have not been done, evidence from the surgical literature suggests that even resource-intensive interventions can be cost effective in comparison to immunizations and human immunodeficiency virus care. In the developing world, where many critically ill patients are younger and have fewer comorbidities, critical care presents a remarkable opportunity to provide significant incremental benefit, arguably much more so than in the developed world. ESSENTIAL CONSIDERATIONS: Key areas of consideration in developing critical care in resource-poor settings include: Personnel and training, equipment and support services, ethics, and research. Strategies for training and retaining skilled labor include tying education to service commitment and developing protocols for even complex processes. Equipment and support services need to focus on technologies that are affordable and sustainable. Ethical decision making must be based on data when possible and on transparent articulated policies always. Research should be performed in resource-poor settings and focus on needs assessment, prognostication, and cost effectiveness. FUTURE DIRECTIONS: The development of critical care in resource-poor settings will rely on the stepwise introduction of service improvements, leveraging human resources through training, a focus on sustainable technology, ongoing analysis of cost effectiveness, and the sharing of context-specific best practices. Although prevention, public health, and disease-specific agendas dominate many current conversations in global health, this is nonetheless a time ripe for the development of critical care. Leaders in global health funding hope to improve quality and length of life. Critical care is an integral part of the continuum of care necessary to make that possible.

Delirium as a predictor of mortality and disability among hospitalized patients in Zambia.

OBJECTIVE: To study the epidemiology and outcomes of delirium among hospitalized patients in Zambia. METHODS: We conducted a prospective cohort study at the University Teaching Hospital in Lusaka, Zambia, from October 2017 to April 2018. The primary exposure was delirium duration over the initial 3 days of hospitalization, assessed daily using the Brief Confusion Assessment Method. The primary outcome was 6-month mortality. Secondary outcomes included 6-month disability, evaluated using the World Health Organization Disability Assessment Schedule 2.0. FINDINGS: 711 adults were included (median age, 39 years; 461 men; 459 medical, 252 surgical; 323 with HIV). Delirium prevalence was 48.5% (95% CI, 44.8%-52.3%). 6-month mortality was higher for delirious participants (44.6% [39.3%-50.1%]) versus non-delirious participants (20.0% [15.4%-25.2%]; P < .001). After adjusting for covariates, delirium duration independently predicted 6-month mortality and disability with a significant dose-response association between number of days with delirium and odds of worse clinical outcome. Compared to no delirium, presence of 1, 2 or 3 days of delirium resulted in odds ratios for 6-month mortality of 1.43 (95% CI, 0.73-2.80), 2.20 (1.07-4.51), and 3.92 (2.24-6.87), respectively (P < .001). Odds of 6-month disability were 1.20 (0.70-2.05), 1.73 (0.95-3.17), and 2.80 (1.78-4.43), respectively (P < .001). CONCLUSION: Among hospitalized medical and surgical patients in Zambia, delirium prevalence was high and delirium duration independently predicted mortality and disability at 6 months. This work lays the foundation for prevention, detection, and management of delirium in low-income countries. Long-term follow up of outcomes of critical illness in resource-limited settings appears feasible using the WHO Disability Assessment Schedule.

Combating information chaos: a case for collaborative clinical guidelines in a pandemic.

The speed and scale of new information during the COVID-19 pandemic required a new approach toward developing best practices and evidence-based clinical guidance. To address this need, we produced COVIDProtocols.org, a collaborative, evidence-based, digital platform for the development and dissemination of COVID-19 clinical guidelines that has been used by over 500,000 people from 196 countries. We use a Collaborative Writing Application (CWA) to facilitate an expedited expert review process and a web platform that deploys content directly from the CWA to minimize any delays. Over 200 contributors have volunteered to create open creative-commons content that spans over 30 specialties and medical disciplines. Multiple local and national governments, hospitals, and clinics have used the site as a key resource for their own clinical guideline development. COVIDprotocols.org represents a model for efficiently launching open-access clinical guidelines during crisis situations to share expertise and combat misinformation.

Sepsis in two hospitals in Rwanda: A retrospective cohort study of presentation, management, outcomes, and predictors of mortality.

PURPOSE: Few studies have assessed the presentation, management, and outcomes of sepsis in low-income countries (LICs). We sought to characterize these aspects of sepsis and to assess mortality predictors in sepsis in two referral hospitals in Rwanda. MATERIALS AND METHODS: This was a retrospective cohort study in two public academic referral hospitals in Rwanda. Data was abstracted from paper medical records of adult patients who met our criteria for sepsis. RESULTS: Of the 181 subjects who met eligibility criteria, 111 (61.3%) met our criteria for sepsis without shock and 70 (38.7%) met our criteria for septic shock. Thirty-five subjects (19.3%) were known to be HIV positive. The vast majority of septic patients (92.7%) received intravenous fluid therapy (median = 1.0 L within 8 hours), and 94.0% received antimicrobials. Vasopressors were administered to 32.0% of the cohort and 46.4% received mechanical ventilation. In-hospital mortality for all patients with sepsis was 51.4%, and it was 82.9% for those with septic shock. Baseline characteristic mortality predictors were respiratory rate, Glasgow Coma Scale score, and known HIV seropositivity. CONCLUSIONS: Septic patients in two public tertiary referral hospitals in Rwanda are young (median age = 40, IQR = 29, 59) and experience high rates of mortality. Predictors of mortality included baseline clinical characteristics and HIV seropositivity status. The majority of subjects were treated with intravenous fluids and antimicrobials. Further work is needed to understand clinical and management factors that may help improve mortality in septic patients in LICs.

Risk factors for delirium among hospitalized patients in Zambia.

OBJECTIVE: To identify risk factors for delirium among hospitalized patients in Zambia. METHODS: We conducted a prospective cohort study at the University Teaching Hospital in Lusaka, Zambia, from October 2017 to April 2018. We report associations of exposures including sociodemographic and clinical factors with delirium over the first three days of hospital admission, assessed using a modified Brief Confusion Assessment Method (bCAM). FINDINGS: 749 patients were included for analysis (mean age, 42.9 years; 64.8% men; 47.3% with HIV). In individual regression analyses of potential delirium risk factors adjusted for age, sex and education, factors significantly associated with delirium included being divorced/widowed (OR 1.64, 95% CI 1.09-2.47), lowest tercile income (OR 1.58, 95% CI 1.04-2.40), informal employment (OR 1.97, 95% CI 1.25-3.15), untreated HIV infection (OR 2.18, 95% CI 1.21-4.06), unknown HIV status (OR 2.90, 95% CI 1.47-6.16), history of stroke (OR 2.70, 95% CI 1.15-7.19), depression/anxiety (OR 1.52, 95% CI 1.08-2.14), alcohol overuse (OR 1.96, 95% CI 1.39-2.79), sedatives ordered on admission (OR 3.77, 95% CI 1.70-9.54), severity of illness (OR 2.00, 95% CI 1.82-2.22), neurological (OR 7.66, 95% CI 4.90-12.24) and pulmonary-system admission diagnoses (OR 1.91, 95% CI 1.29-2.85), and sepsis (OR 2.44, 95% CI 1.51-4.08). After combining significant risk factors into a multivariable regression analysis, severity of illness, history of stroke, and being divorced/widowed remained predictive of delirium (p<0.05). CONCLUSION: Among hospitalized adults at a national referral hospital in Zambia, severity of illness, history of stroke, and being divorced/widowed were independently predictive of delirium. Extension of this work will inform future efforts to prevent, detect, and manage delirium in low- and middle-income countries.

Ultrasound versus Computed Tomography Assessment of Focal Lung Aeration in Invasively Ventilated ICU Patients.

It is unknown whether and to what extent the penetration depth of lung ultrasound (LUS) influences the accuracy of LUS findings. The current study evaluated and compared the LUS aeration score and two frequently used B-line scores with focal lung aeration assessed by chest computed tomography (CT) at different levels of depth in invasively ventilated intensive care unit (ICU) patients. In this prospective observational study, patients with a clinical indication for chest CT underwent a 12-region LUS examination shortly before CT scanning. LUS images were compared with corresponding regions on the chest CT scan at different subpleural depths. For each LUS image, the LUS aeration score was calculated. LUS images with B-lines were scored as the number of separately spaced B-lines (B-line count score) and the percentage of the screen covered by B-lines divided by 10 (B-line percentage score). The fixed-effect correlation coefficient (ß) was presented per 100 Hounsfield units. A total of 40 patients were included, and 372 regions were analyzed. The best association between the LUS aeration score and CT was found at a subpleural depth of 5 cm for all LUS patterns (ß = 0.30, p < 0.001), 1 cm for A- and B1-patterns (ß = 0.10, p < 0.001), 6 cm for B1- and B2-patterns (ß = 0.11, p < 0.001) and 4 cm for B2- and C-patterns (ß = 0.07, p = 0.001). The B-line percentage score was associated with CT (ß = 0.46, p = 0.001), while the B-line count score was not (ß = 0.07, p = 0.305). In conclusion, the subpleural penetration depth of ultrasound increased with decreased aeration reflected by the LUS pattern. The LUS aeration score and the B-line percentage score accurately reflect lung aeration in ICU patients, but should be interpreted while accounting for the subpleural penetration depth of ultrasound.

The role for high flow nasal cannula as a respiratory support strategy in adults: a clinical practice guideline.

PURPOSE: High flow nasal cannula (HFNC) is a relatively recent respiratory support technique which delivers high flow, heated and humidified controlled concentration of oxygen via the nasal route. Recently, its use has increased for a variety of clinical indications. To guide clinical practice, we developed evidence-based recommendations regarding use of HFNC in various clinical settings. METHODS: We formed a guideline panel composed of clinicians, methodologists and experts in respiratory medicine. Using GRADE, the panel developed recommendations for four actionable questions. RESULTS: The guideline panel made a strong recommendation for HFNC in hypoxemic respiratory failure compared to conventional oxygen therapy (COT) (moderate certainty), a conditional recommendation for HFNC following extubation (moderate certainty), no recommendation regarding HFNC in the peri-intubation period (moderate certainty), and a conditional recommendation for postoperative HFNC in high risk and/or obese patients following cardiac or thoracic surgery (moderate certainty). CONCLUSIONS: This clinical practice guideline synthesizes current best-evidence into four recommendations for HFNC use in patients with hypoxemic respiratory failure, following extubation, in the peri-intubation period, and postoperatively for bedside clinicians.

Global Critical Care: Moving Forward in Resource-Limited Settings.

Caring for critically ill patients is challenging in resource-limited settings, where the burden of disease and mortality from potentially treatable illnesses is higher than in resource-rich areas. Barriers to delivering quality critical care in these settings include lack of epidemiologic data and context-specific evidence for medical decision-making, deficiencies in health systems organization and resources, and institutional obstacles to implementation of life-saving interventions. Potential solutions include the development of common definitions for intensive care unit (ICU), intensivist, and intensive care to create a universal ICU organization framework; development of educational programs for capacity building of health care professionals working in resource-limited settings; global prioritization of epidemiologic and clinical research in resource-limited settings to conduct timely and ethical studies in response to emerging threats; adaptation of international guidelines to promote implementation of evidence-based care; and strengthening of health systems that integrates these interventions. This manuscript reviews the field of global critical care, barriers to safe high-quality care, and potential solutions to existing challenges. We also suggest a roadmap for improving the treatment of critically ill patients in resource-limited settings.