Elisabeth D. Riviello

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.

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.

A Survey on Critical Care Resources and Practices in Low- and Middle-Income Countries

BACKGROUND Timely and appropriate care is the key to achieving good outcomes in acutely ill patients, but the effectiveness of critical care may be limited in resource-limited settings. OBJECTIVES This study sought to understand how to implement best practices in intensive care units (ICU) in low- and middle-income countries (LMIC) and to develop a point-of-care training and decision-support tool. METHODS An internationally representative group of clinicians performed a 22-item capacity-and-needs assessment survey in a convenience sample of 13 ICU in Eastern Europe (4), Asia (4), Latin America (3), and Africa (2), between April and July 2012. Two ICU were from low-income, 2 from low-middle-income, and 9 from upper-middle-income countries. Clinician respondents were asked about bed capacity, patient characteristics, human resources, available medications and equipment, access to education, and processes of care. RESULTS Thirteen clinicians from each of 13 hospitals (1 per ICU) responded. Surveyed hospitals had median of 560 (interquartile range [IQR]: 232, 1,200) beds. ICU had a median of 9 (IQR: 7, 12) beds and treated 40 (IQR: 20, 67) patients per month. Many ICU had ≥ 1 staff member with some formal critical care training (n = 9, 69%) or who completed Fundamental Critical Care Support (n = 7, 54%) or Advanced Cardiac Life Support (n = 9, 69%) courses. Only 2 ICU (15%) used any kind of checklists for acute resuscitation. Ten (77%) ICU listed lack of trained staff as the most important barrier to improving the care and outcomes of critically ill patients. CONCLUSIONS In a convenience sample of 13 ICU from LMIC, specialty-trained staff and standardized processes of care such as checklists are frequently lacking. ICU needs-assessment evaluations should be expanded in LMIC as a global priority, with the goal of creating and evaluating context-appropriate checklists for ICU best practices.

Acute respiratory distress syndrome in the global context.

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 ARDSs 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.

Sepsis research and the poorest of the poor

www.thelancet.com/infection Vol 15 May 2015 501 8 Cohen J, Vincent J-L, Adhikari NKJ, et al. Sepsis: a roadmap for future research. Lancet Infect Dis 2015; 15: 581–614. 9 Miller RR 3rd, Dong L, Nelson NC, Brown SM, Kuttler KG, Probst DR, Allen TL, Clemmer TP, for the Intermountain Healthcare Intensive Medicine Clinical Program. Multicenter implementation of a severe sepsis and septic shock treatment bundle. Am J Respir Crit Care Med 2013; 188: 77–82. 10 Yealy DM, Kellum JA, Huang DT, et al, for the PROCESS investigators. A randomized trial of protocol-based care for early septic shock. N Engl J Med 2014, 370: 1683–93. 11 Shankar-Hari M, Deutschman CS, Singer M. Do we need a new defi nition of sepsis? Int Care Med 2015; published online Feb 3. DOI:10.1007/s00134015-3680-x. 12 NHS England. Patient safety alert—resources to support the prompt recognition of sepsis and the rapid initiation of treatment. Sept 2, 2014. https://www.england.nhs.uk/2014/09/02/psa-sepsis/0 (accessed April 1, 2015). 13 Parliamentary and Health Service Ombudsman. Time to act. Severe sepsis: rapid diagnosis and treatment saves lives. http://www.ombudsman.org. uk/__data/assets/pdf_fi le/0004/22666/FINAL_Sepsis_Report_web.pdf (accessed April 1, 2015). 1 Kissoon N, Carcillo JA, Espinosa V, et al, for the Global Sepsis Initiative Vanguard Center Contributors. World Federation of Pediatric Intensive Care and Critical Care Societies: global sepsis initiative. Pediatr Crit Care Med 2011; 12: 494–503. 2 Hall MJ, Williams SN, DeFrances CJ, Golosinskiy A. Inpatient care for septicemia or sepsis: a challenge for patients and hospitals. NCHS data brief. Hyattsville, MD: National Center for Health Statistics, 2011. http:// www.cdc.gov/nchs/data/databriefs/db62.htm (accessed April 1, 2015). 3 Seymour CW, Rea TD, Kahn JM, Walkey AJ, Yealy DM, Angus DC. Severe sepsis in pre-hospital emergency care: analysis of incidence, care, and outcome. Am J Respir Crit Care Med 2012; 186: 1264–71. 4 Davydow DS, Giff ord JM, Desai SV, Needham DM, Bienvenu OJ. Posttraumatic stress disorder in general intensive care unit survivors: a systematic review. Gen Hosp Psychiatry 2008; 30: 421–34. 5 Iwashyna TJ, Ely EW, Smith DM, Langa KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010, 304: 1787–94. 6 WHO. WHO global report: mortality attributable to tobacco. Geneva: World Health Organization, 2012. http://www.who.int/tobacco/publications/ surveillance/rep_mortality_attributable/en/ (accessed April 1, 2015). 7 Zilberberg MD, Shorr AF, Micek ST, Vazquez-Guillamet C, Kollef MH. Multi-drug resistance, inappropriate initial antibiotic therapy and mortality in Gram-negative severe sepsis and septic shock: a retrospective cohort study. Critical Care 2014; 18: 596.

Predicting mortality in low-income country icus: The Rwanda mortality probability model (R-MPM)

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.

Concurrent cryptococcal meningitis and disseminated tuberculosis occurring in an immunocompetent male

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 patients 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.

Insuficiencia renal aguda en la unidad de cuidados intensivos

A pesar de los avances técnicos en los últimos años en el tratamiento de la insuficiencia renal aguda (IRA), los pacientes críticos con esta complicación presentan una mortalidad muy elevada. Así, desde 1970 hasta 2004, los pacientes ingresados en unidades de cuidados intensivos (UCI) con IRA presentan una mortalidad que poco ha variado y que se sitúa alrededor del 50%1. Un estudio prospectivo y observacional, realizado en unos 30.000 pacientes de UCI, halló una incidencia de IRA del 5,7%, de los que en casi la mitad la causa más probable era el shock séptico2. Lo más llamativo era que los pacientes que desarrollaban IRA o que precisaban tratamiento sustitutivo renal (TSR) presentaban una mortalidad hospitalaria del 60,3%. Se ha observado que, en la IRA, un retraso en la consulta a nefrología se asocia con mayor morbilidad y mortalidad, independientemente de la necesidad o no de TSR3. La IRA es un proceso habitualmente multifactorial, lo que explica el hecho que la mayoría de estudios hayan sido poco concluyentes y que no se haya podido progresar demasiado en mejorar el pronóstico de esta entidad4. Recientemente, se han realizado esfuerzos para definir y clasificar de modo preciso la IRA5. Si bien se han ensayado muchos métodos para prevenir la IRA, actualmente el control de la volemia y de la circulación, junto con la precaución en el uso de nefrotóxicos, siguen siendo los pilares de la prevención primaria6. De la misma manera, mientras que se han ensayado múltiples intervenciones farmacológicas para el tratamiento temprano de la IRA7, el TSR sigue siendo el tratamiento principal de la IRA en la UCI6. Nuestro conocimiento de las posibilidades del TSR se ha expandido en los últimos años, de manera que en la actualidad se emplea en indicaciones no estrictamente nefrológicas8. En este artículo, se revisan algunos aspectos prácticos del cuidado nefrológico en las UCI, como es la definición de IRA, las indicaciones de TSR, los parámetros de TSR, incluidos el momento de inicio, la modalidad, la dosis y la anticoagulación, así como 2 aspectos nuevos que pueden cambiar la atención nefrológica en las UCI, como es la hemofiltración de alto volumen (HFAV) y la emergencia de nuevos marcadores urinarios de lesión renal.

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.

Development and internal validation of the Simplified Mortality Score for the Intensive Care Unit (SMS-ICU)

Dear Sir We congratulate the authors on the development and validation of a simplified critical care prognostic model using a combined (predominantly) European clinical trial data set and the adherence to the TRIPOD statement. Work undertaken by our groups in resourcelimited settings has demonstrated challenges in the development and application of relatively simple prognostic models such as APACHE II. Missing predictor variables, lack of post-ICU outcome measures, poor clinical uptake of scores due to perceived complexity and poor adherence to guidelines such as TRIPOD transcend healthcare settings. As data missingness is widespread in resource-limited settings, we support the a priori decision to exclude variables with missingness > 25% and to utilise multiple imputation to address lesser proportions of missingness. Indeed, the traditional strategy of normal imputation for missing data is inappropriate. Recognising the need for using ‘real-life’ pragmatic data sets when developing and validating prognostic models, we suggest wider applicability of the methods described in their paper, in particular including Low-and-Middle Income Countries (LMICs). We also suggest cross-validation of simplified prognostic models developed in both High Income Countries and LMICs. This will also provide insights into generalisability of the models across diverse settings, with regard to differences in casemix, available healthcare facilities and variations in presentation. In addition to efforts to refine statistical methodology to improve model performance, the development of prognostic tools should be in the context of ‘real world’ performance and impact on patient outcomes. This highlights additional aspects for the successful operationalisation of these models. For settings where electronic health information settings are rare, implementation of clinician-led, settingadapted contemporaneous electronic tools aiding frontline care, but enabling medical registry and research functionality can provide an alternative. Active engagement with healthcare workers, both doctors and nursing staff, is essential to ensure uptake of the information provided by a scoring system: collaborative projects initiated by our groups are ongoing in both lowand middle-income countries. We invite the authors to share their thoughts on the opinion that research is warranted to better understand the priorities of clinicians, researchers and administrators, when developing or advocating any prognostic model.