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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 Pa O 2 :Fi O 2  ⩽ 300 mm Hg or oxygen saturation as measured by pulse oximetry Sp O 2 :Fi O 2  ⩽ 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.

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., Competing Interests: KR reports consulting fees from Janssen Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Brotherton, Joshi, Otieno, Wandia, Gitura, Mueller, Nguyen, Letchford, Riviello, Karanja and Rudd.)

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., Competing Interests: Disclosure Department of Veterans Affairs Tennessee Valley Health Care System Geriatric Research, Education and Clinical Center (GRECC) and VA-MERIT, the National Institutes of Health under awards (R01AG027472, R01AG035117, R01HL111111, R01GM120484, and R01AG058639)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.

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., (© 2021. The Author(s).)

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 (β) 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 (β = 0.30, p < 0.001), 1 cm for A- and B1-patterns (β = 0.10, p < 0.001), 6 cm for B1- and B2-patterns (β = 0.11, p < 0.001) and 4 cm for B2- and C-patterns (β = 0.07, p = 0.001). The B-line percentage score was associated with CT (β = 0.46, p = 0.001), while the B-line count score was not (β = 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., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Covidprotocols.org has been financially supported by USAID, USAID’s Sustaining Technical and Analytic Resources (STAR) project, and the John Doerr Family Foundation. The remaining authors have no disclosures or conflicts of interest relevant to this work. E.Y.K. is a co-investigator in NCT04389671 (Windtree Therapeutics) testing lucinactant (surfactant-like treatment) in COVID-19 patients. E.Y.K. has received unrelated research funding from Bayer, the U.S. National Institutes of Health, the American Heart Association, the American Lung Association, and the American Thoracic Society., (© 2021 The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: Dr. Ely has received research grants and/or honoraria from Hospira, Orion, Pfizer and Abbott. Dr. Heimburger has received honoraria from Danone Institute North America. The remaining authors report no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Dr. Ely has received research grants and/or honoraria from Hospira, Orion, Pfizer and Abbott. The remaining authors report no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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.

Competing Interests: Competing Interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest.

Rationale: Despite oxygen's classification as an essential medication by the World Health Organization, it is inconsistently available in many resource-constrained settings. Hypoxemia is associated with increased mortality, and mounting evidence suggests that hyperoxia may also be associated with adverse outcomes. Objectives: To determine if overuse of oxygen for some patients in a Rwandan tertiary care hospital emergency department might coexist with oxygen shortages and underuse of oxygen for other patients, and whether an educational intervention coupled with provision of pulse oximeters could improve the distribution of limited oxygen resources. Methods: We screened all patients in the adult emergency department (ED) of the University Teaching Hospital of Kigali for hypoxemia and receipt of oxygen therapy for 5 weeks. After completing baseline data collection, we provided pulse oximeters and conducted a didactic training with pre- and posttests on oxygen titration, with a chosen target oxygen saturation (Sp O 2 ) of 90% to 95%. Four and 12 weeks after the intervention, we evaluated all patients in the ED again for Sp O 2 and receipt of oxygen therapy for 4 weeks each period. We also recorded ED oxygen use and availability of reserve oxygen for the hospital during the three study periods. Results: During all data collection periods, 214 of 1,765 (12.1%) unique patients screened were hypoxemic. The proportion of patient-days with appropriately titrated oxygen therapy (Sp O 2 , 90-95%) increased from 18.7% at baseline to 38.5% and 42.0% at 4 and 12 weeks postintervention ( P  < 0.001). On a multiple-choice examination testing knowledge of appropriate oxygen titration, clinicians' scores improved from average 60% (interquartile range [IQR], 40-80%) correct to 80% (IQR, 60-80%) correct immediately after the educational intervention ( P  < 0.001). Oxygen use in the ED decreased from a median of 32.0 (IQR, 28.0-35.0) tanks per day to 25.5 (IQR, 24.0-29.0) and 16.0 (IQR, 12.5-21.0) tanks per day at Weeks 4 and 12, respectively ( P  < 0.001), and the median daily number of tanks in reserve for the hospital appeared to increase, although this did not reach statistical significance (30.0 [IQR, 9.0-46.0], 86.5 [IQR, 74.0-92.0], and 75.5 [IQR, 8.5-88.5], respectively; P  = 0.07). Conclusions: Among patients in a Rwandan adult ED, 12.1% of patients were hypoxemic and 81.3% of patient-days were either under- or overtreated with oxygen during baseline data collection on the basis of our defined target of Sp O 2 90% to 95%. Follow-up results at 4 and 12 weeks postintervention demonstrated sustained improvement in oxygen titration and likely increased availability of oxygen resources.

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., Competing Interests: The authors have declared that no competing interests exist.

Background: Semi-quantification of lung aeration by ultrasound helps to assess presence and extent of pulmonary pathologies, including the acute respiratory distress syndrome (ARDS). It is uncertain which lung regions add most to the diagnostic accuracy for ARDS of the frequently used global lung ultrasound (LUS) score. We aimed to compare the diagnostic accuracy of the global versus those of regional LUS scores in invasively ventilated intensive care unit patients., Methods: This was a post-hoc analysis of a single-center observational study in the mixed medical-surgical intensive care unit of a university-affiliated hospital in the Netherlands. Consecutive patients, aged ≥ 18 years, and are expected to receive invasive ventilation for > 24 h underwent a LUS examination within the first 2 days of ventilation. The Berlin Definition was used to diagnose ARDS, and to classify ARDS severity. From the 12-region LUS examinations, the global score (minimum 0 to maximum 36) and 3 regional scores (the 'anterior,' 'lateral,' and 'posterior' score, minimum 0 to maximum 12) were computed. The area under the receiver operating characteristic (AUROC) curve was calculated and the best cutoff for ARDS discrimination was determined for all scores., Results: The study enrolled 152 patients; 35 patients had ARDS. The global score was higher in patients with ARDS compared to patients without ARDS (median 19 [15-23] vs. 5 [3-9]; P < 0.001). The posterior score was the main contributor to the global score, and was the only score that increased significantly with ARDS severity. However, the posterior score performed worse than the global score in diagnosing ARDS, and it had a positive predictive value of only 50 (41-59)% when using the optimal cutoff. The combined anterolateral score performed as good as the global score (AUROC of 0.91 [0.85-0.97] vs. 0.91 [0.86-0.95])., Conclusions: While the posterior score increases with ARDS severity, its diagnostic accuracy for ARDS is hampered due to an unfavorable signal-to-noise ratio. An 8-region 'anterolateral' score performs as well as the global score and may prove useful to exclude ARDS in invasively ventilated ICU patients.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Background: This systematic review and meta-analysis summarizes the safety and efficacy of high flow nasal cannula (HFNC) in patients with acute hypoxemic respiratory failure., Methods: We performed a comprehensive search of MEDLINE, EMBASE, and Web of Science. We identified randomized controlled trials that compared HFNC to conventional oxygen therapy. We pooled data and report summary estimates of effect using relative risk for dichotomous outcomes and mean difference or standardized mean difference for continuous outcomes, with 95% confidence intervals. We assessed risk of bias of included studies using the Cochrane tool and certainty in pooled effect estimates using GRADE methods., Results: We included 9 RCTs (n = 2093 patients). We found no difference in mortality in patients treated with HFNC (relative risk [RR] 0.94, 95% confidence interval [CI] 0.67-1.31, moderate certainty) compared to conventional oxygen therapy. We found a decreased risk of requiring intubation (RR 0.85, 95% CI 0.74-0.99) or escalation of oxygen therapy (defined as crossover to HFNC in the control group, or initiation of non-invasive ventilation or invasive mechanical ventilation in either group) favouring HFNC-treated patients (RR 0.71, 95% CI 0.51-0.98), although certainty in both outcomes was low due to imprecision and issues related to risk of bias. HFNC had no effect on intensive care unit length of stay (mean difference [MD] 1.38 days more, 95% CI 0.90 days fewer to 3.66 days more, low certainty), hospital length of stay (MD 0.85 days fewer, 95% CI 2.07 days fewer to 0.37 days more, moderate certainty), patient reported comfort (SMD 0.12 lower, 95% CI 0.61 lower to 0.37 higher, very low certainty) or patient reported dyspnea (standardized mean difference [SMD] 0.16 lower, 95% CI 1.10 lower to 1.42 higher, low certainty). Complications of treatment were variably reported amongst included studies, but little harm was associated with HFNC use., Conclusion: In patients with acute hypoxemic respiratory failure, HFNC may decrease the need for tracheal intubation without impacting mortality.

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., Competing Interests: The authors have no competing interests to declare., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/.)

Introduction: Patients with severe malaria or sepsis are at risk of developing life-threatening acute respiratory distress syndrome (ARDS). The objective of this study was to evaluate point-of-care lung ultrasound as a novel tool to determine the prevalence and early signs of ARDS in a resource-limited setting among patients with severe malaria or sepsis., Materials and Methods: Serial point-of-care lung ultrasound studies were performed on four consecutive days in a planned sub study of an observational cohort of patients with malaria or sepsis in Bangladesh. We quantified aeration patterns across 12 lung regions. ARDS was defined according to the Kigali Modification of the Berlin Definition., Results: Of 102 patients enrolled, 71 had sepsis and 31 had malaria. Normal lung ultrasound findings were observed in 44 patients on enrolment and associated with 7% case fatality. ARDS was detected in 10 patients on enrolment and associated with 90% case fatality. All patients with ARDS had sepsis, 4 had underlying pneumonia. Two patients developing ARDS during hospitalisation already had reduced aeration patterns on enrolment. The SpO2/FiO2 ratio combined with the number of regions with reduced aeration was a strong prognosticator for mortality in patients with sepsis (AUROC 91.5% (95% Confidence Interval: 84.6%-98.4%))., Conclusions: This study demonstrates the potential usefulness of point-of-care lung ultrasound to detect lung abnormalities in patients with malaria or sepsis in a resource-constrained hospital setting. LUS was highly feasible and allowed to accurately identify patients at risk of death in a resource limited setting., Competing Interests: The authors have declared that no competing interests exist.

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.

In Table 1 of this article, the numerical data were correct but the graphic part was imprecise.

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.

Introduction: Intensive Care Unit (ICU) risk prediction models are used to compare outcomes for quality improvement initiatives, benchmarking, and research. While such models provide robust tools in high-income countries, an ICU risk prediction model has not been validated in a low-income country where ICU population characteristics are different from those in high-income countries, and where laboratory-based patient data are often unavailable. We sought to validate the Mortality Probability Admission Model, version III (MPM0-III) in two public ICUs in Rwanda and to develop a new Rwanda Mortality Probability Model (R-MPM) for use in low-income countries., Methods: We prospectively collected data on all adult patients admitted to Rwanda's two public ICUs between August 19, 2013 and October 6, 2014. We described demographic and presenting characteristics and outcomes. We assessed the discrimination and calibration of the MPM0-III model. Using stepwise selection, we developed a new logistic model for risk prediction, the R-MPM, and used bootstrapping techniques to test for optimism in the model., Results: Among 427 consecutive adults, the median age was 34 (IQR 25-47) years and mortality was 48.7%. Mechanical ventilation was initiated for 85.3%, and 41.9% received vasopressors. The MPM0-III predicted mortality with area under the receiver operating characteristic curve of 0.72 and Hosmer-Lemeshow chi-square statistic p = 0.024. We developed a new model using five variables: age, suspected or confirmed infection within 24 hours of ICU admission, hypotension or shock as a reason for ICU admission, Glasgow Coma Scale score at ICU admission, and heart rate at ICU admission. Using these five variables, the R-MPM predicted outcomes with area under the ROC curve of 0.81 with 95% confidence interval of (0.77, 0.86), and Hosmer-Lemeshow chi-square statistic p = 0.154., Conclusions: The MPM0-III has modest ability to predict mortality in a population of Rwandan ICU patients. The R-MPM is an alternative risk prediction model with fewer variables and better predictive power. If validated in other critically ill patients in a broad range of settings, the model has the potential to improve the reliability of comparisons used for critical care research and quality improvement initiatives in low-income countries.

A 61-year-old man living in rural Rwanda presented with a 2-month history of fevers, headaches, dry cough, weight loss and confusion. A cerebrospinal fluid analysis revealed neutrophilic pleocytosis, yeast and a positive cryptococcal antigen (CrAg). An HIV antibody test was negative. The patient's cough worsened while on antifungal induction therapy with intravenous conventional amphotericin B and high-dose oral fluconazole. Computerised tomography (CT) scan of the chest showed extensive miliary infiltrates. Bronchoalveolar lavage revealed acid-fast bacilli on smear and a positive GeneXpert test without rifampicin resistance. The patient improved with the addition of antitubercular therapy. In this case report, we describe an unusual presentation of two opportunistic infections occurring together in an HIV-negative man with no other known immunocompromising conditions. The case highlights the fact that, in disease endemic areas, multiple disseminated infections can occur in individuals without obvious immunocompromise., (2016 BMJ Publishing Group Ltd.)

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.

Background: The reality of finite resources has a real-world impact on a patient's ability to receive life-saving care in resource-poor settings. Blood for transfusion is an example of a scarce resource. Very few studies have looked at predictors of survival in patients requiring massive transfusion. We used data from a rural hospital in Kenya to develop a prediction model of survival among patients receiving massive transfusion., Methods: Patients who received five or more units of whole blood within 48 hours between 2004 and 2010 were identified from a blood registry in a rural hospital in Kenya. Presenting characteristics and in-hospital survival were collected from charts. Using stepwise selection, a logistic model was developed to predict who would survive with massive transfusion versus those who would die despite transfusion. An ROC curve was created from this model to quantify its predictive power., Results: Ninety-five patients with data available met inclusion criteria, and 74% survived to discharge. The number of units transfused was not a predictor of mortality, and no threshold for futility could be identified. Preliminary results suggest that initial blood pressure, lack of comorbidities, and indication for transfusion are the most important predictors of survival. The ROC curve derived from our model demonstrates an area under the curve (AUC) equal to 0.757, with optimism of 0.023 based on a bootstrap validation., Conclusions: This study provides a framework for making prioritization decisions for the use of whole blood in the setting of massive bleeding. Our analysis demonstrated an overall survival rate for patients receiving massive transfusion that was higher than clinical perception. Our analysis also produced a preliminary model to predict survival in patients with massive bleeding. Prediction analyses can contribute to more efficient prioritization decisions; these decisions must also include other considerations such as equity, acceptability, affordability and sustainability.

Acute respiratory distress syndrome (ARDS) is a clinically defined syndrome of hypoxia and bilateral pulmonary infiltrates due to inflammatory pathways triggered by pulmonary and nonpulmonary insults, and ARDS is pathologically correlated with diffuse alveolar damage. Estimates of ARDS's impact in the developed world vary widely, with some of the discrepancies attributed to marked differences in the availability of intensive care beds and mechanical ventilation. Almost nothing is known about the epidemiology of ARDS in the developing world, in part due to a clinical definition requiring positive pressure ventilation, arterial blood gases, and chest radiography. Current frameworks for comparing the epidemiology of death and disability across the world including the GBD (Global Burden of Disease Study) 2010 are ill-suited to quantifying critical illness syndromes including ARDS. Modifications to the definition of ARDS to allow a provision for environments without the capacity for positive pressure ventilation, and to allow for alternate diagnostic techniques including pulse oximetry and ultrasound, may make it possible to quantify and describe the impact of ARDS in the global context., (Copyright © 2014 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

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.

While gadolinium was initially thought to be a safe alternative to iodinated contrast agents for patients with chronic renal insufficiency, many reports of gadolinium-associated acute renal failure have now been recorded, particularly in patients with underlying renal insufficiency. In addition, animal models have demonstrated tubule vacuolization with experimental gadolinium administration that is similar to vacuolization seen with other contrast agents. We present a case of a patient with nephrotic-range proteinuria and chronic renal insufficiency, who developed acute renal failure following gadolinium administration undergoing furosemide stimulated diuresis. This case is the first report of pathologic tubule vacuolization in gadolinium-associated nephropathy in a human kidney biopsy. This case suggests a relationship between the pathogenesis of CIN with standard contrast media and CIN with gadolinium. Research is needed to better understand the pathologic findings and pathogenesis of gadolinium-associated nephrotoxicity.

Few detailed epidemiologic data exist regarding the impact of HIV infection on the workplace in the developing world. In addition, most HIV surveys examine only prevalence, without data on incidence or disease severity. In June 2003, we conducted a voluntary anonymous HIV serosurvey among employees of the Debswana Mining Company, the largest nongovernmental employer in Botswana. Among the 3558 participants, annual HIV incidence was estimated to be 3.4%, and HIV prevalence was 23.8%. HIV-infected participants had a median CD4(+) lymphocyte count of 427 cells/mm(3) (interquartile range 269-642), with 13.3% of samples <200 cells/mm(3). The high incidence and prevalence of HIV, and the proportion of workers with <200 CD4(+) lymphocytes/mm(3), demonstrate the impact of HIV infection in this workplace and the potential negative impact on productivity. These results highlight the need for routine HIV testing and access to antiretro-viral treatment for workers in countries such as Botswana.