ATS REPORTS Global Health Series Editor: Gustavo Matute-Bello, M.D.
Global Health Care of the Critically Ill in Low-Resource Settings Srinivas Murthy1,2 and Neill K. Adhikari1,3 1 Inderdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada; 2Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; and 3Department of Critical Care Medicine and Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Abstract The care of the critically ill patient in low-resource settings is challenging because of many factors, including limitations in the existing infrastructure, lack of disposables, and low numbers of trained healthcare workers. Although cost constraints in lowresource settings have traditionally caused critical care to be relegated to a low priority, ethical issues and the potential for mitigation of the lethal effects of often reversible acute conditions, such as sepsis and traumatic hemorrhage, argue for prudent deployment of critical care resources. Given these challenges, issues that require prioritization include timely and reliable delivery of evidence-based or generally
accepted interventions to acutely ill patients before the development of organ failure, context-specific adaptation and evaluation of clinical evidence, and sustained investments in quality improvement and health systems strengthening. Specific examples include fluid resuscitation algorithms for patients with sepsis and reliable, low-cost, high-flow oxygen concentrators for patients with pneumonia. The lessons from new research on clinical management and sustainable education and quality improvement approaches will likely improve the care of critically ill patients worldwide. Keywords: global health; critical care; sepsis; developing countries
(Received in original form July 28, 2013; accepted in final form July 30, 2013 ) Correspondence and requests for reprints should be addressed to Neill Adhikari, M.D., M.Sc., Sunnybrook Health Sciences Center, 2075 Bayview Ave., Toronto, ON, M4N 3M5 Canada. E-mail: [email protected] Ann Am Thorac Soc Vol 10, No 5, pp 509–513, Oct 2013 Copyright © 2013 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201307-246OT Internet address: www.atsjournals.org
The care of the critically ill patient is a global enterprise. Throughout the world and regardless of geographic location or associated capabilities of the healthcare system, patients present to hospitals with life-threatening illnesses. Although the capacity of modern critical care has grown tremendously over recent decades, much of the world lacks the resources to implement its high-cost and resourceintensive management strategies, despite the globally asymmetric distribution of critically ill patients (Figure 1) (1–3). Therefore, strategies to prevent and manage critical illness must be extrapolated to regions where diagnostic, monitoring and therapeutic technologies widely available in high-income countries are lacking. ATS Reports
However, this approach is fraught with challenges, given variation in disease burden, patient demographics, and infrastructure of the healthcare system. Meeting these challenges requires contextspecific clinical evidence, qualityimprovement activities, and the ongoing development of a robust health system, including approaches to prevent critical illness in at-risk hospitalized patients. In this paper, we discuss the challenges of providing critical care in low-resource settings as well as low-cost adaptations of critical care–specific strategies and areas of research. We also discuss the care of selected critical illness syndromes in lowresource settings, including management strategies and current guidelines.
The Difficulties of Critical Care in Under-Resourced Regions The provision of critical care is complex, regardless of location. Interdisciplinary team-based care with high-technology monitoring and interventions will invariably generate high costs, including costs associated with capital equipment and consumables; salaries for nurses, other allied health personnel, and physicians; and health system costs for long-term survivors. Although intensive care units (ICUs) can choose which technologies and drugs to provide, none of these costs are entirely avoidable, and some are comparable globally. For example, daily ICU costs in Indian private hospitals are similar to North 509
ATS REPORTS
Figure 1. Deaths potentially preventable with critical care, by country income. Data are from Global Burden of Disease (56) and are based on official national data, disease modeling, or family recollection of the cause of death. We assume that all acute conditions, including trauma, ischemic heart disease, pneumonia, and other acute infections that could lead to a fatal outcome, are relevant for determining the global burden of critical illness. The burden of critical illness is seen to be primarily in low- and middle-income settings.
America, with an additional burden imposed by the need to obtain and maintain functional equipment and ensure reliable electricity and oxygen supply (4, 5). The high fixed costs of critical care, in addition to a traditional view that acute care lies outside public health mandates, likely explain the severe limitations of critical care infrastructure in lowresource settings (1) and at least partially explain the limited ability to implement recommended management strategies for sepsis—even those that are relatively inexpensive—across Africa and parts of Asia (6, 7). Setting aside salary costs, the paucity of appropriately trained personnel to provide advanced-level care in much of the world remains a major challenge. For example, Nigeria has only 380 critical care nurses for a population of 140 million, compared with more than 500,000 critical care nurses in the United States for a population of 314 million (8, 9). Training opportunities remain sparse, given the geographic inequalities in critical care unit distribution. Existing ICUs are often staffed by providers who have partially trained in high-income regions and are thus more likely to emigrate, further depleting personnel. Finally, reimbursement mechanisms for intensive care physicians are typically disorganized and relatively underfunded, as the specialty is not formally recognized in many jurisdictions (10). Another challenge to providing critical care to acutely ill patients in much of the world is the requirement for direct payment by the patient or family members (11). Even 510
if potentially life-saving interventions are available at moderate cost, the financial penalty to the family may be substantial. Given the long-term costs of critical care survivors, especially with high rates of readmission (12, 13), families may not be able to cope, complicating medical decision-making; by contrast, in highincome countries financial considerations are often not part of the healthcare decision-making process (14).
Low-Cost, High-Yield, Preventive Critical Care The definition and implementation of effective critical care in cost-constrained settings, therefore, remain to be fully elucidated. Although critical care in lowresource settings may be viewed as contrary to good public health policy, arguments favoring the provision of critical care stem from ethical obligations to rescue acutely ill patients and to meet population expectations for health care (15). Additionally, there is the potential for selected relatively inexpensive critical care interventions and systems to reverse potentially lethal conditions, such as sepsis and hemorrhage from trauma or obstetric catastrophes. Given the challenges endemic in limited-resource areas, issues that require prioritization include timely and reliable delivery of evidence-based or generally accepted interventions to acutely ill patients before the development of organ failure, context-specific adaptation and evaluation of clinical evidence, and sustained
investments in efforts directed at improving quality and strengthening existing health systems. Excluded from this list is the isolated introduction of new and expensive equipment into ICUs. Meeting these challenges extends beyond the ICU. Outside the hospital, effective and safe patient transportation systems are required to transfer critically ill patients between hospitals. Within hospitals, the emergency department, operating theaters, and wards must be well-structured to recognize and initially manage acutely ill patients, for example, by implementation of guidelines for sepsis management and stabilization of trauma patients (16). Triage and critical care admission standards must be locally adapted to ensure that there is optimal flow of patients through the ICU and that limited critical care resources are distributed effectively (17, 18). Scoring systems for triage have considerable theoretical appeal as tools to identify deteriorating patients but require further refinement, as currently available scores may not have adequate predictive power in low-resource settings (19). Similarly, currently available ICU mortality prediction tools, useful for risk adjustment for benchmarking and quality improvement activities, need to be revalidated in region-specific contexts (20, 21). Within the ICU, the lack of trained staff and practice-support tools, such as protocols, checklists, standard order sets, and guidelines, speaks to the substantial opportunities to develop and provide lowcost, high-yield intensive care in costconstrained regions (22). Implementing these improvements in a scalable, feasible, sustainable, and successful manner will require governmental, professional, and institutional endorsement.
Disease-Specific Considerations Sepsis
The burden of sepsis in developing countries is very high, given that it is the final common pathway toward death for a variety of acute infections (23). Global guidelines for sepsis have been published by the Surviving Sepsis Campaign, highlighting the importance of early recognition, fluid
AnnalsATS Volume 10 Number 5 | October 2013
ATS REPORTS resuscitation, source-control measures, and antibiotic therapy (24). Many of the recommended interventions, however, require tools and monitoring capabilities that are inaccessible for many district and regional hospitals globally (6, 7, 25). Additionally, blind adoption of established interventions in high-income settings may prove to be ineffective in lower-income settings; this has been shown with aggressive fluid boluses for children with sepsis (26). Hence, much of the current evidence base for sepsis management may require significant adaptation for the majority of the world’s patients with sepsis. As a first step, consensus-based guidelines have recently been published to assist care providers in these resource-limited settings (27, 28). Given the diagnostic challenges of severe sepsis, there has been high interest in biomarkers for the early recognition and triage of the patient with sepsis among those presenting with vital sign abnormalities and a presumed infection. Point-of-care tests for serum lactic acid, glucose, and hemoglobin levels are currently available and can be used to triage and monitor selected patients with and without sepsis (29–31), although none has currently been demonstrated to improve outcomes across a range of settings. The general themes of management in the Surviving Sepsis Guidelines, notably fluid resuscitation and antibiotics, can be adapted to resource-limited settings (32). For example, intensive fluid resuscitation to target normalization of vital signs and restoration of urine output has been the traditional mainstay of management and can be feasibly administered in the absence of advanced hemodynamic monitoring (33). In anemic African children with severe sepsis, however, fluid boluses should be minimized, given the risk for increased mortality (26). Evidence from clinical trials does not support the choice of colloid over crystalloid solutions, and hence crystalloids are recommended due to their availability and cost (34). Earlier blood transfusions may be beneficial, especially in children with sepsis, although this intervention requires further specific study in resource-limited settings (26). Delivery of recommended vasopressors for septic shock may be challenging, given the need for infusion pumps and preference for central venous access. Source control through removal or debridement of known ATS Reports
infected tissues should be performed at the earliest possible opportunity (35). Prompt therapy with broad-spectrum antibiotics tailored toward the presumed source of infection and local epidemiology is crucial. Finally, organizational quality improvement interventions, such as standardized center- and region-specific protocols that incorporate local epidemiology and resources, are promising tools to improve outcomes (25, 33, 36).
freely available from the World Health Organization (WHO) and include management protocols adapted to lowresource settings (28, 44). Although selected aspects of the pediatric and adult guidelines have been studied, they are largely based on expert opinion, and rigorous evaluations of their implementation are required.
Trauma Severe Acute Respiratory Infection
Pneumonia (in the absence of septic shock) is another major source of mortality globally (23). Physiological support for patients with pneumonia is contingent on the availability of oxygen and mechanical ventilation, without which treatment is limited to antibiotics and source control in patients with concomitant empyema. The availability of pulse oximetry, alongside oxygen systems, has been shown to improve clinical outcomes (37). The consistent availability of oxygen cylinders, however, is limited in many centers due to significant storage and transport costs (4, 37, 38). Novel and cost-effective technology, such as oxygen concentrators that are capable of flow rates between 5 and 10 L/min and of supplying multiple patients simultaneously, may improve availability of oxygen (39, 40). Mechanical ventilators and anesthesia machines designed to meet the challenges of resource-limited settings (i.e., those that are easy to service, have prolonged battery life, and are affordable) are available and becoming less expensive (41–43). However, their dissemination has been slow, due to a lack of trained clinicians and institutional reticence. As in high-resource settings, mechanical ventilation strategies for low-resource regions will depend on patient factors including the etiology of respiratory failure and lung mechanics. Challenges to the safe delivery of mechanical ventilation in these settings include maintaining a reliable supply of important disposables (filters, circuits), training and retaining biomedical engineers for ventilator maintenance, and ensuring patient safety when arterial blood gas analyzers are not available. Similar to sepsis, integrated management guidelines for children and adults with severe respiratory distress are
The burden of hospitalization and death due to trauma continues to increase, especially among working-age adolescents and adults, with worse outcomes in low-income regions (23, 45). WHO recommendations for trauma care are common to all settings and include a rapid assessment to ascertain the extent and nature of the injuries using a systematic and team-based approach, including management of airway emergencies, hemorrhage control and resuscitation, and cervical spine stabilization (46). Based on a large global clinical trial, tranexamic acid to decrease bleeding is recommended in any trauma patient with significant hemorrhage (47). Similarly, a coordinated hospital team-based approach has been shown to improve provider expertise and clinical outcomes in a variety of settings (48, 49), and further refinements based on integration into trauma protocols of point-of-care testing such as hemoglobin assays and ultrasound may expedite definitive management and improve outcomes (50). Definitive management of the trauma patient typically involves surgical repair and often requires timely referral to a higher level of care, given variable accessibility of operating theaters and trained personnel (51). Recent data demonstrate the high burden of surgical illness globally (51–53) as well as opportunities for improving outcomes using educational and qualityimprovement programs (54). Protocols for triage and early management of specific injuries are available from the WHO Integrated Management of Adolescent and Adult Illness (IMAI) district clinician manual and the Surgical Care at the District Hospital manual (28, 46). Similar to protocols for sepsis and severe acute respiratory infection, however, these require adaptation to specific regions followed by evaluation to ensure their applicability (54, 55). 511
ATS REPORTS Conclusions In high-income and some high-middle– income countries, the survival benefits from critical care depend primarily on the availability of skilled professionals, the existing infrastructure, and technological solutions that are inaccessible to the nearly
half of the global population living in other regions. However, as new research on clinical management, sustainable education, and quality improvement is conducted and disseminated (26, 56), it will likely become possible to more effectively, cheaply, sustainably, and successfully manage severely ill patients in
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ATS REPORTS 33 Jacob ST, Banura P, Baeten JM, Moore CC, Meya D, Nakiyingi L, Burke R, Horton CL, Iga B, Wald A, et al.; Promoting ResourceLimited Interventions for Sepsis Management in Uganda Study Group. The impact of early monitored management on survival in hospitalized adult Ugandan patients with severe sepsis: a prospective intervention study. Crit Care Med 2012;40: 2050–2058. 34 Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247–2256. 35 Marshall JC, al Naqbi A. Principles of source control in the management of sepsis. Crit Care Clin 2009;25:753–768. (viii–ix.). 36 Pollach G, Namboya F. Preventing Intensive Care Admissions for Sepsis in Tropical Africa (PICASTA): an extension of the International Pediatric Global Sepsis Initiative: an African Perspective. Pediatr Crit Care Med 2013;14:561–570. 37 Duke T, Graham SM, Cherian MN, Ginsburg AS, English M, Howie S, Peel D, Enarson PM, Wilson IH, Were W; Union Oxygen Systems Working Group. Oxygen is an essential medicine: a call for international action. Int J Tuberc Lung Dis 2010;14:1362–1368. 38 Hill SE, Njie O, Sanneh M, Jallow M, Peel D, Njie M, Weber M, Hill PC, Adegbola RA, Howie SR. Oxygen for treatment of severe pneumonia in The Gambia, West Africa: a situational analysis. Int J Tuberc Lung Dis 2009;13:587–593. 39 Duke T, Peel D, Graham S, Howie S, Enarson PM, Jacobson R. Oxygen concentrators: a practical guide for clinicians and technicians in developing countries. Ann Trop Paediatr 2010;30: 87–101. 40 Duke T, Peel D, Wandi F, Subhi R, Sa’avu M, Matai S. Oxygen supplies for hospitals in Papua New Guinea: a comparison of the feasibility and cost-effectiveness of methods for different settings. P N G Med J 2010;53:126–138. 41 Beringer RM, Eltringham RJ. The Glostavent: evolution of an anaesthetic machine for developing countries. Anaesth Intensive Care 2008;36:442–448. 42 Khambatta HJ, Westheimer DN, Power RW, Kim Y, Flood T. Safe, lowtechnology anesthesia system for medical missions to remote locations. Anesthesiology 2006;104:1354–1356. 43 Rana R, Manik L, Manandar ML, Raj S. The universal anesthesia machine towards achieving MDG5 in Nepal. Br J Anesth 2012;108: ii109–ii144.
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44 Pocket Book of Hospital Care for Children. Geneva: World Health Organization; 2013. 45 Mock CN, Adzotor KE, Conklin E, Denno DM, Jurkovich GJ. Trauma outcomes in the rural developing world: comparison with an urban level I trauma center. J Trauma 1993;35:518–523. 46 Surgical Care at the District Hospital. Geneva: World Health Organization; 2003. 47 Roberts I, Shakur H, Afolabi A, Brohi K, Coats T, Dewan Y, Gando S, Guyatt G, Hunt BJ, Morales C, et al.; CRASH-2 Collaborators. The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial. Lancet 2011;377:1096–1101. 48 Bergman S, Deckelbaum D, Lett R, Haas B, Demyttenaere S, Munthali V, Mbembati N, Museru L, Razek T. Assessing the impact of the trauma team training program in Tanzania. J Trauma 2008;65: 879–883. 49 Meaney PA, Topjian AA, Chandler HK, Botha M, Soar J, Berg RA, Nadkarni VM. Resuscitation training in developing countries: a systematic review. Resuscitation 2010;81:1462–1472. 50 Smith ZA, Postma N, Wood D. FAST scanning in the developing world emergency department. S Afr Med J 2010;100:105–108. 51 Funk LM, Weiser TG, Berry WR, Lipsitz SR, Merry AF, Enright AC, Wilson IH, Dziekan G, Gawande AA. Global operating theatre distribution and pulse oximetry supply: an estimation from reported data. Lancet 2010;376:1055–1061. 52 Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, Gawande AA. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet 2008; 372:139–144. 53 Groen RS, Samai M, Kamara TB, Kushner AL. The unmet surgical disease burden in the developing world. Lancet 2012;379:616. 54 Maru DS, Schwarz R, Schwarz D, Andrews J, Panizales MT, Karelas G, Brady JS, Rogers S. Implementing surgical services in a rural, resource-limited setting: a study protocol. BMJ Open 2011;1: e000166. 55 Henry JA, Orgoi S, Govind S, Price RR, Lundeg G, Kehrer B. Strengthening surgical services at the soum (first-referral) hospital: the WHO emergency and essential surgical care (EESC) program in Mongolia. World J Surg 2012;36:2359–2370. 56 Mathers C, Fat DM, Boerma JT, World Health Organization. The global burden of disease: 2004 update. Geneva, Switzerland: World Health Organization; 2008.
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Global Health Care of the Critically Ill in Low-Resource Settings Srinivas Murthy1,2 and Neill K. Adhikari1,3 1 Inderdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada; 2Department of Critical Care Medicine, Hospital for Sick Children, Toronto, Ontario, Canada; and 3Department of Critical Care Medicine and Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
Abstract The care of the critically ill patient in low-resource settings is challenging because of many factors, including limitations in the existing infrastructure, lack of disposables, and low numbers of trained healthcare workers. Although cost constraints in lowresource settings have traditionally caused critical care to be relegated to a low priority, ethical issues and the potential for mitigation of the lethal effects of often reversible acute conditions, such as sepsis and traumatic hemorrhage, argue for prudent deployment of critical care resources. Given these challenges, issues that require prioritization include timely and reliable delivery of evidence-based or generally
accepted interventions to acutely ill patients before the development of organ failure, context-specific adaptation and evaluation of clinical evidence, and sustained investments in quality improvement and health systems strengthening. Specific examples include fluid resuscitation algorithms for patients with sepsis and reliable, low-cost, high-flow oxygen concentrators for patients with pneumonia. The lessons from new research on clinical management and sustainable education and quality improvement approaches will likely improve the care of critically ill patients worldwide. Keywords: global health; critical care; sepsis; developing countries
(Received in original form July 28, 2013; accepted in final form July 30, 2013 ) Correspondence and requests for reprints should be addressed to Neill Adhikari, M.D., M.Sc., Sunnybrook Health Sciences Center, 2075 Bayview Ave., Toronto, ON, M4N 3M5 Canada. E-mail: [email protected] Ann Am Thorac Soc Vol 10, No 5, pp 509–513, Oct 2013 Copyright © 2013 by the American Thoracic Society DOI: 10.1513/AnnalsATS.201307-246OT Internet address: www.atsjournals.org
The care of the critically ill patient is a global enterprise. Throughout the world and regardless of geographic location or associated capabilities of the healthcare system, patients present to hospitals with life-threatening illnesses. Although the capacity of modern critical care has grown tremendously over recent decades, much of the world lacks the resources to implement its high-cost and resourceintensive management strategies, despite the globally asymmetric distribution of critically ill patients (Figure 1) (1–3). Therefore, strategies to prevent and manage critical illness must be extrapolated to regions where diagnostic, monitoring and therapeutic technologies widely available in high-income countries are lacking. ATS Reports
However, this approach is fraught with challenges, given variation in disease burden, patient demographics, and infrastructure of the healthcare system. Meeting these challenges requires contextspecific clinical evidence, qualityimprovement activities, and the ongoing development of a robust health system, including approaches to prevent critical illness in at-risk hospitalized patients. In this paper, we discuss the challenges of providing critical care in low-resource settings as well as low-cost adaptations of critical care–specific strategies and areas of research. We also discuss the care of selected critical illness syndromes in lowresource settings, including management strategies and current guidelines.
The Difficulties of Critical Care in Under-Resourced Regions The provision of critical care is complex, regardless of location. Interdisciplinary team-based care with high-technology monitoring and interventions will invariably generate high costs, including costs associated with capital equipment and consumables; salaries for nurses, other allied health personnel, and physicians; and health system costs for long-term survivors. Although intensive care units (ICUs) can choose which technologies and drugs to provide, none of these costs are entirely avoidable, and some are comparable globally. For example, daily ICU costs in Indian private hospitals are similar to North 509
ATS REPORTS
Figure 1. Deaths potentially preventable with critical care, by country income. Data are from Global Burden of Disease (56) and are based on official national data, disease modeling, or family recollection of the cause of death. We assume that all acute conditions, including trauma, ischemic heart disease, pneumonia, and other acute infections that could lead to a fatal outcome, are relevant for determining the global burden of critical illness. The burden of critical illness is seen to be primarily in low- and middle-income settings.
America, with an additional burden imposed by the need to obtain and maintain functional equipment and ensure reliable electricity and oxygen supply (4, 5). The high fixed costs of critical care, in addition to a traditional view that acute care lies outside public health mandates, likely explain the severe limitations of critical care infrastructure in lowresource settings (1) and at least partially explain the limited ability to implement recommended management strategies for sepsis—even those that are relatively inexpensive—across Africa and parts of Asia (6, 7). Setting aside salary costs, the paucity of appropriately trained personnel to provide advanced-level care in much of the world remains a major challenge. For example, Nigeria has only 380 critical care nurses for a population of 140 million, compared with more than 500,000 critical care nurses in the United States for a population of 314 million (8, 9). Training opportunities remain sparse, given the geographic inequalities in critical care unit distribution. Existing ICUs are often staffed by providers who have partially trained in high-income regions and are thus more likely to emigrate, further depleting personnel. Finally, reimbursement mechanisms for intensive care physicians are typically disorganized and relatively underfunded, as the specialty is not formally recognized in many jurisdictions (10). Another challenge to providing critical care to acutely ill patients in much of the world is the requirement for direct payment by the patient or family members (11). Even 510
if potentially life-saving interventions are available at moderate cost, the financial penalty to the family may be substantial. Given the long-term costs of critical care survivors, especially with high rates of readmission (12, 13), families may not be able to cope, complicating medical decision-making; by contrast, in highincome countries financial considerations are often not part of the healthcare decision-making process (14).
Low-Cost, High-Yield, Preventive Critical Care The definition and implementation of effective critical care in cost-constrained settings, therefore, remain to be fully elucidated. Although critical care in lowresource settings may be viewed as contrary to good public health policy, arguments favoring the provision of critical care stem from ethical obligations to rescue acutely ill patients and to meet population expectations for health care (15). Additionally, there is the potential for selected relatively inexpensive critical care interventions and systems to reverse potentially lethal conditions, such as sepsis and hemorrhage from trauma or obstetric catastrophes. Given the challenges endemic in limited-resource areas, issues that require prioritization include timely and reliable delivery of evidence-based or generally accepted interventions to acutely ill patients before the development of organ failure, context-specific adaptation and evaluation of clinical evidence, and sustained
investments in efforts directed at improving quality and strengthening existing health systems. Excluded from this list is the isolated introduction of new and expensive equipment into ICUs. Meeting these challenges extends beyond the ICU. Outside the hospital, effective and safe patient transportation systems are required to transfer critically ill patients between hospitals. Within hospitals, the emergency department, operating theaters, and wards must be well-structured to recognize and initially manage acutely ill patients, for example, by implementation of guidelines for sepsis management and stabilization of trauma patients (16). Triage and critical care admission standards must be locally adapted to ensure that there is optimal flow of patients through the ICU and that limited critical care resources are distributed effectively (17, 18). Scoring systems for triage have considerable theoretical appeal as tools to identify deteriorating patients but require further refinement, as currently available scores may not have adequate predictive power in low-resource settings (19). Similarly, currently available ICU mortality prediction tools, useful for risk adjustment for benchmarking and quality improvement activities, need to be revalidated in region-specific contexts (20, 21). Within the ICU, the lack of trained staff and practice-support tools, such as protocols, checklists, standard order sets, and guidelines, speaks to the substantial opportunities to develop and provide lowcost, high-yield intensive care in costconstrained regions (22). Implementing these improvements in a scalable, feasible, sustainable, and successful manner will require governmental, professional, and institutional endorsement.
Disease-Specific Considerations Sepsis
The burden of sepsis in developing countries is very high, given that it is the final common pathway toward death for a variety of acute infections (23). Global guidelines for sepsis have been published by the Surviving Sepsis Campaign, highlighting the importance of early recognition, fluid
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ATS REPORTS resuscitation, source-control measures, and antibiotic therapy (24). Many of the recommended interventions, however, require tools and monitoring capabilities that are inaccessible for many district and regional hospitals globally (6, 7, 25). Additionally, blind adoption of established interventions in high-income settings may prove to be ineffective in lower-income settings; this has been shown with aggressive fluid boluses for children with sepsis (26). Hence, much of the current evidence base for sepsis management may require significant adaptation for the majority of the world’s patients with sepsis. As a first step, consensus-based guidelines have recently been published to assist care providers in these resource-limited settings (27, 28). Given the diagnostic challenges of severe sepsis, there has been high interest in biomarkers for the early recognition and triage of the patient with sepsis among those presenting with vital sign abnormalities and a presumed infection. Point-of-care tests for serum lactic acid, glucose, and hemoglobin levels are currently available and can be used to triage and monitor selected patients with and without sepsis (29–31), although none has currently been demonstrated to improve outcomes across a range of settings. The general themes of management in the Surviving Sepsis Guidelines, notably fluid resuscitation and antibiotics, can be adapted to resource-limited settings (32). For example, intensive fluid resuscitation to target normalization of vital signs and restoration of urine output has been the traditional mainstay of management and can be feasibly administered in the absence of advanced hemodynamic monitoring (33). In anemic African children with severe sepsis, however, fluid boluses should be minimized, given the risk for increased mortality (26). Evidence from clinical trials does not support the choice of colloid over crystalloid solutions, and hence crystalloids are recommended due to their availability and cost (34). Earlier blood transfusions may be beneficial, especially in children with sepsis, although this intervention requires further specific study in resource-limited settings (26). Delivery of recommended vasopressors for septic shock may be challenging, given the need for infusion pumps and preference for central venous access. Source control through removal or debridement of known ATS Reports
infected tissues should be performed at the earliest possible opportunity (35). Prompt therapy with broad-spectrum antibiotics tailored toward the presumed source of infection and local epidemiology is crucial. Finally, organizational quality improvement interventions, such as standardized center- and region-specific protocols that incorporate local epidemiology and resources, are promising tools to improve outcomes (25, 33, 36).
freely available from the World Health Organization (WHO) and include management protocols adapted to lowresource settings (28, 44). Although selected aspects of the pediatric and adult guidelines have been studied, they are largely based on expert opinion, and rigorous evaluations of their implementation are required.
Trauma Severe Acute Respiratory Infection
Pneumonia (in the absence of septic shock) is another major source of mortality globally (23). Physiological support for patients with pneumonia is contingent on the availability of oxygen and mechanical ventilation, without which treatment is limited to antibiotics and source control in patients with concomitant empyema. The availability of pulse oximetry, alongside oxygen systems, has been shown to improve clinical outcomes (37). The consistent availability of oxygen cylinders, however, is limited in many centers due to significant storage and transport costs (4, 37, 38). Novel and cost-effective technology, such as oxygen concentrators that are capable of flow rates between 5 and 10 L/min and of supplying multiple patients simultaneously, may improve availability of oxygen (39, 40). Mechanical ventilators and anesthesia machines designed to meet the challenges of resource-limited settings (i.e., those that are easy to service, have prolonged battery life, and are affordable) are available and becoming less expensive (41–43). However, their dissemination has been slow, due to a lack of trained clinicians and institutional reticence. As in high-resource settings, mechanical ventilation strategies for low-resource regions will depend on patient factors including the etiology of respiratory failure and lung mechanics. Challenges to the safe delivery of mechanical ventilation in these settings include maintaining a reliable supply of important disposables (filters, circuits), training and retaining biomedical engineers for ventilator maintenance, and ensuring patient safety when arterial blood gas analyzers are not available. Similar to sepsis, integrated management guidelines for children and adults with severe respiratory distress are
The burden of hospitalization and death due to trauma continues to increase, especially among working-age adolescents and adults, with worse outcomes in low-income regions (23, 45). WHO recommendations for trauma care are common to all settings and include a rapid assessment to ascertain the extent and nature of the injuries using a systematic and team-based approach, including management of airway emergencies, hemorrhage control and resuscitation, and cervical spine stabilization (46). Based on a large global clinical trial, tranexamic acid to decrease bleeding is recommended in any trauma patient with significant hemorrhage (47). Similarly, a coordinated hospital team-based approach has been shown to improve provider expertise and clinical outcomes in a variety of settings (48, 49), and further refinements based on integration into trauma protocols of point-of-care testing such as hemoglobin assays and ultrasound may expedite definitive management and improve outcomes (50). Definitive management of the trauma patient typically involves surgical repair and often requires timely referral to a higher level of care, given variable accessibility of operating theaters and trained personnel (51). Recent data demonstrate the high burden of surgical illness globally (51–53) as well as opportunities for improving outcomes using educational and qualityimprovement programs (54). Protocols for triage and early management of specific injuries are available from the WHO Integrated Management of Adolescent and Adult Illness (IMAI) district clinician manual and the Surgical Care at the District Hospital manual (28, 46). Similar to protocols for sepsis and severe acute respiratory infection, however, these require adaptation to specific regions followed by evaluation to ensure their applicability (54, 55). 511
ATS REPORTS Conclusions In high-income and some high-middle– income countries, the survival benefits from critical care depend primarily on the availability of skilled professionals, the existing infrastructure, and technological solutions that are inaccessible to the nearly
half of the global population living in other regions. However, as new research on clinical management, sustainable education, and quality improvement is conducted and disseminated (26, 56), it will likely become possible to more effectively, cheaply, sustainably, and successfully manage severely ill patients in
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