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.

Attitudes, beliefs, and practices toward end-of-life care among physicians in sub-Saharan Africa.

Introduction: as the opportunity to receive life-sustaining treatments expands in sub-Saharan Africa (SSA), so do potential ethical dilemmas. Little is known regarding the attitudes, beliefs, and practices of physicians in SSA regarding end-of-life care ethics. Methods: we used validated survey items addressing physician end-of-life care views and added SSA-context specific items. We identified a convenience sample using the authors' existing African professional contacts and snowball recruitment. Participants were invited via email to an anonymous online survey. Results: we contacted 78 physicians who practice critical care in Africa, and 68% (n=53) completed the survey. Of those, 66% were male, 55% were aged 36-45, 75% were Christian. They were from Kenya (30%), Zambia (28%), Rwanda (25%), Botswana (11%), and other countries (6%). Most (75%) agreed that competent patients can refuse even life-saving care. Only 32% agreed that their hospital had clear policies regarding withdrawing and withholding care, 11% agreed that their country had legal precedent for end-of-life care, and 43% believed that doctors could face legal or financial consequences for allowing patients to die by forgoing treatment. Pain control at the end of life, even if it may hasten death, was supported by 83%. However, 75% felt that clinicians undertreat pain due to fear of hastening death. Conclusion: participants strongly supported patient autonomy and end-of-life pain control but expressed concern that inadequate policy and legal frameworks exist to guide care and that pain is undertreated. Humane and actionable end-of-life care frameworks are needed to guide decisions in SSA.

Oxygen saturation targets for adults with acute hypoxemia in low and lower-middle income countries: a scoping review with analysis of contextual factors.

Knowing the target oxygen saturation (SpO2) range that results in the best outcomes for acutely hypoxemic adults is important for clinical care, training, and research in low-income and lower-middle income countries (collectively LMICs). The evidence we have for SpO2 targets emanates from high-income countries (HICs), and therefore may miss important contextual factors for LMIC settings. Furthermore, the evidence from HICs is mixed, amplifying the importance of specific circumstances. For this literature review and analysis, we considered SpO2 targets used in previous trials, international and national society guidelines, and direct trial evidence comparing outcomes using different SpO2 ranges (all from HICs). We also considered contextual factors, including emerging data on pulse oximetry performance in different skin pigmentation ranges, the risk of depleting oxygen resources in LMIC settings, the lack of access to arterial blood gases that necessitates consideration of the subpopulation of hypoxemic patients who are also hypercapnic, and the impact of altitude on median SpO2 values. This process of integrating prior study protocols, society guidelines, available evidence, and contextual factors is potentially useful for the development of other clinical guidelines for LMIC settings. We suggest that a goal SpO2 range of 90-94% is reasonable, using high-performing pulse oximeters. Answering context-specific research questions, such as an optimal SpO2 target range in LMIC contexts, is critical for advancing equity in clinical outcomes globally.

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.

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.

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.

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.

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.

Predicting mortality in adults with suspected infection in a Rwandan hospital: an evaluation of the adapted MEWS, qSOFA and UVA scores.

RATIONALE: Mortality prediction scores are increasingly being evaluated in low and middle income countries (LMICs) for research comparisons, quality improvement and clinical decision-making. The modified early warning score (MEWS), quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), and Universal Vital Assessment (UVA) score use variables that are feasible to obtain, and have demonstrated potential to predict mortality in LMIC cohorts. OBJECTIVE: To determine the predictive capacity of adapted MEWS, qSOFA and UVA in a Rwandan hospital. DESIGN, SETTING, PARTICIPANTS AND OUTCOME MEASURES: We prospectively collected data on all adult patients admitted to a tertiary hospital in Rwanda with suspected infection over 7 months. We calculated an adapted MEWS, qSOFA and UVA score for each participant. The predictive capacity of each score was assessed including sensitivity, specificity, positive and negative predictive value, OR, area under the receiver operating curve (AUROC) and performance by underlying risk quartile. RESULTS: We screened 19 178 patient days, and enrolled 647 unique patients. Median age was 35 years, and in-hospital mortality was 18.1%. The proportion of data missing for each variable ranged from 0% to 11.7%. The sensitivities and specificities of the scores were: adapted MEWS >4, 50.4% and 74.9%, respectively; qSOFA >2, 24.8% and 90.4%, respectively; and UVA >4, 28.2% and 91.1%, respectively. The scores as continuous variables demonstrated the following AUROCs: adapted MEWS 0.69 (95% CI 0.64 to 0.74), qSOFA 0.65 (95% CI 0.60 to 0.70), and UVA 0.71 (95% CI 0.66 to 0.76); there was no statistically significant difference between the discriminative capacities of the scores. CONCLUSION: Three scores demonstrated a modest ability to predict mortality in a prospective study of inpatients with suspected infection at a Rwandan tertiary hospital. Careful consideration must be given to their adequacy before using them in research comparisons, quality improvement or clinical decision-making.

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.

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.

Widespread antimicrobial resistance among bacterial infections in a Rwandan referral hospital.

BACKGROUND: Resistance among bacterial infections is increasingly well-documented in high-income countries; however, relatively little is known about bacterial antimicrobial resistance in low-income countries, where the burden of infections is high. METHODS: We prospectively screened all adult inpatients at a referral hospital in Rwanda for suspected infection for seven months. Blood, urine, wound and sputum samples were cultured and tested for antibiotic susceptibility. We examined factors associated with resistance and compared hospital outcomes for participants with and without resistant isolates. RESULTS: We screened 19,178 patient-days, and enrolled 647 unique participants with suspected infection. We obtained 942 culture specimens, of which 357 were culture-positive specimens. Of these positive specimens, 155 (43.4%) were wound, 83 (23.2%) urine, 64 (17.9%) blood, and 55 (15.4%) sputum. Gram-negative bacteria comprised 323 (88.7%) of all isolates. Of 241 Gram-negative isolates tested for ceftriaxone, 183 (75.9%) were resistant. Of 92 Gram-negative isolates tested for the extended spectrum beta-lactamase (ESBL) positive phenotype, 66 (71.7%) were ESBL positive phenotype. Transfer from another facility, recent surgery or antibiotic exposure, and hospital-acquired infection were each associated with resistance. Mortality was 19.6% for all enrolled participants. CONCLUSIONS: This is the first published prospective hospital-wide antibiogram of multiple specimen types from East Africa with ESBL testing. Our study suggests that low-resource settings with limited and inconsistent access to the full range of antibiotic classes may bear the highest burden of resistant infections. Hospital-acquired infections and recent antibiotic exposure are associated with a high proportion of resistant infections. Efforts to slow the development of resistance and supply effective antibiotics are urgently needed.