Our evolving understanding of the physiologic processes that lead to sepsis has led to updated consensus guidelines outlining priorities in the recognition and treatment of septic patients. However, an enormous question remains when considering how to best implement these guidelines in settings with limited resources, which include rural US emergency departments and low- and middle-income countries. The core principles of sepsis management should be a priority in community emergency departments. Similarly, cost-effective interventions are key priorities in low- and middle-income countries; however, consideration must be given to the unique challenges associated with such settings.
Key points
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Protocols may aid identification and initial treatment of patients presenting with sepsis to community emergency departments.
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Aggressive fluid resuscitation and early administration of antimicrobials are key to effective care.
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Major differences, including patient characteristics and resource availability, limit the generalizability of current sepsis guidelines to low- and middle-income countries.
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Further research, specific to low-resource settings, is necessary to set priorities for expanding sepsis care globally.
Introduction
As we have seen throughout this issue, the approach to identifying and treating sepsis can be complicated. Additionally, most research investigating the best practices in identifying and treating sepsis has been done in large academic centers in high-income countries (HICs). Despite the recommendations, studies show that the current sepsis guidelines can be difficult to carry out in both large academic emergency departments (EDs) and low- and middle-income countries (LMICs). Limiting factors such as equipment availability and staffing issues can be found not only in low-resource settings but also in HICs. Additionally, the failure of sepsis protocols in some LMICs leads to questions about how we classify sepsis in these settings. How do providers in community EDs (CED) translate the results of these studies into daily practice? Which are the most cost-effective strategies in delivering quality sepsis care with limited resources? This article focuses on sepsis in low-resource settings, ranging from a CED in the United States to hospitals in LMICs. This article identifies the most common barriers to providing quality sepsis care, recommendations for maximizing current resources, and priorities for future directions of care.
Introduction
As we have seen throughout this issue, the approach to identifying and treating sepsis can be complicated. Additionally, most research investigating the best practices in identifying and treating sepsis has been done in large academic centers in high-income countries (HICs). Despite the recommendations, studies show that the current sepsis guidelines can be difficult to carry out in both large academic emergency departments (EDs) and low- and middle-income countries (LMICs). Limiting factors such as equipment availability and staffing issues can be found not only in low-resource settings but also in HICs. Additionally, the failure of sepsis protocols in some LMICs leads to questions about how we classify sepsis in these settings. How do providers in community EDs (CED) translate the results of these studies into daily practice? Which are the most cost-effective strategies in delivering quality sepsis care with limited resources? This article focuses on sepsis in low-resource settings, ranging from a CED in the United States to hospitals in LMICs. This article identifies the most common barriers to providing quality sepsis care, recommendations for maximizing current resources, and priorities for future directions of care.
Surviving sepsis in the community
Guidelines and Sepsis Bundles
The 2012 Surviving Sepsis Campaign (SSC) Guidelines, although generally based on research in large academic centers, are designed to allow initiation of sepsis care in any setting, including CEDs. The current guidelines represent a modified version of the original guidelines released in 2004. In the years after the publication of the original guidelines, several studies looked at complete and component specific compliance with the guidelines. The 2 largest of these, conducted in academic centers around the world, found that compliance with the complete bundle overall was less than 30%. The individual components with the highest compliance were measurement of lactate (61%–78%), obtaining blood cultures (64%–84%), fluid/vasopressor initiation (60%–77%), and ventilator plateau-pressure control (80%–85%). A study of implementation in a CED had similar results, finding that although patients often received antimicrobials (78%) and vasopressors (79%), few received central venous pressure measurement (27%) or central venous oxygen saturation measurement (15%). Despite the overall low compliance, it was believed that increased compliance led to improved mortality outcomes.
It was, therefore, generally accepted that overall, protocol-based care was beneficial, even if there was debate on which components should be included. The revised 2012 SSC guidelines continued to promote protocol-based care, but the individual components were streamlined to include only those that had solid supporting evidence.
The concept of strict protocol-based care, however, has since been called into question, as several large studies found no mortality difference compared with standard care. However, a more recent study seems to confirm the benefits of protocol-based care. There are several proposed reasons for the variation in these results largely involving a change in usual care provided in sepsis management and the complex infrastructure and resources required for protocol implementation.
Early Recognition of Sepsis
Early recognition of sepsis is critical and yet provides potentially the greatest obstacle in achieving further improvements in decreased mortality. Recognition ideally begins in the prehospital setting and in triage where increased education and improved screening protocols for suspected sepsis reduce time to diagnosis and treatment. However, a subjective component remains involved in the diagnosis of sepsis such that the provider has to attribute systemic dysfunction to an underlying infectious process. Early recognition is challenging in first-world large academic EDs let alone in CEDs or LMICS.
Measuring Lactate
Serum lactate is classically thought to result from anaerobic metabolism, either systemic or regional, and it is used as a surrogate marker for tissue hypoperfusion. An elevated serum lactate level is associated with worse outcomes in septic patients. In recent sepsis trials, an elevated lactate was found in 30% to 50% of patients without hypotension and was found to be associated with increased mortality independent of blood pressure. For this reason, early measurement of serum lactate is necessary to avoid the missing patients with so-called “cryptic shock”(ie, lactate ≥4 mmol/L and normotension).
Consequently, early lactate testing in patients suspected of having sepsis should be part of standard practice. In most cases, the costs associated with testing can be offset by the costs associated with earlier recognition and treatment. Point-of-care lactate correlates well with laboratory lactate and is preferred, as it leads to expedited diagnosis and treatment. The costs of point-of-care compared with laboratory lactates vary depending on institution.
Antimicrobials
Numerous studies have shown that early administration of appropriate antibiotics improves outcomes in septic patients, other studies have shown mixed results, and still others have shown no benefit. So does time to antibiotics matter? The answer of course is, it depends. Most studies that show mortality benefits for early antibiotics were done in patients with septic shock. There is some evidence that this also extends to the elevated lactate (≥4 mmol/L) group (regardless of blood pressure). When looking at less-severe septic patients or grouping all sepsis patients together, the results are less impressive. What is perhaps most notable is that no study has ever used the 3-hour rule that the guidelines use as a benchmark.
How does this translate to the CED or LMIC? In general, the goal should be to strive for early and appropriate antimicrobial administration. In patients with severe sepsis and septic shock, earlier is better. However, appropriate antibiotic therapy is also important. Inappropriate antibiotics (ie, antibiotic did not cover isolated pathogen) can lead to increased mortality. Thus, any ED protocol for septic patients should include triggers for empiric antibiotics for patients with severe sepsis and septic shock. These broad-spectrum antibiotics should be immediately available in the ED and based on the ED antibiogram.
Fluid Resuscitation
The complex physiologic processes of sepsis that lead to tissue hypoperfusion are still being elucidated. As of now, it is thought that this is caused by some combination of decreased circulating volume, increased insensible losses, and vasodilation, which is compounded in certain cases by cardiac, renal, and other end-organ dysfunction. The guidelines recommend a 30-mL/kg crystalloid fluid bolus for patients with hypotension or elevated lactate. The actual practice of fluid resuscitation, however, is much more complex than this and is covered in (See Rob Loflin and Michael E. Winters’ article, “ Fluid Resuscitation in Severe Sepsis ”, in this issue).
The choice of which fluids to use for resuscitation in sepsis is an ongoing debate. The current general consensus is that we should choose crystalloids over colloids, and lactated Ringer’s is preferable to normal saline. The amount of fluids required for resuscitation is patient specific. At the time of recognition of severe sepsis or septic shock, a 30-mL/kg bolus is recommended. Then, reassessment of the patient’s fluid status is recommended before any additional fluid administration ( Fig. 1 ).
Miscellaneous Recommendations
Staff resources
Although emergency physicians are ultimately responsible for identifying and treating septic patients, sepsis is a resource intensive disease, and numerous ED health care personnel are involved. Nurse-driven protocols assist in earlier identification of septic patients and decreased time to obtaining blood cultures, lactate, and administering antibiotics. Conversely, insufficient nursing resources have been cited as a barrier to implementation of sepsis guidelines. Based on these findings, a nurse-driven protocol, including methods to allow temporary one-to-one nursing care, should be developed to facilitate compliance with sepsis guidelines. These methods can be further enhanced with the development of nurse or physician “champions” who promote sepsis education and provide feedback to foster a team-based culture for treating sepsis.
Transfer decisions
One of the most important decisions to consider for a septic patient presenting to a CED is their ultimate disposition. The decision to admit to the floor versus intensive care unit (ICU) is often simplified in community settings based on the lack of monitoring availability outside of the ICU. However, does the patient require transfer? This decision will vary widely by location based on transport times and resources in the community hospital. Often, patients with severe sepsis and septic shock will be transferred out of a CED. This can, however, delay time to appropriate resuscitation and antibiotic administration. The approach to sepsis transfers should be similar to that of trauma transfers. Consideration for transfer should begin immediately when recognizing that a patient may exceed institutional capabilities. The priority, however, should be initiation of aggressive fluid resuscitation and antibiotic administration while simultaneously arranging early transfer.
Summary of Goals of Sepsis Care in the Community Emergency Department or Low- and Middle-Income Country Emergency Department
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Nearly all sepsis management research has been done in large academic centers.
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Lack of benefit in the literature from sepsis protocols is likely a result of overall improvements in care and knowledge of guidelines.
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Protocols may benefit community hospitals by streamlining care and improving adherence to guidelines.
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Protocols should include prehospital or triage screening for sepsis.
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Point-of-care lactate measurement is easy to perform, can identify patients at risk for bad outcomes, and can be followed as a resuscitation endpoint.
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Blood cultures should be drawn early without impeding antibiotic delivery.
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Appropriate broad-spectrum antimicrobials should be given as early as possible and readily available to nurses.
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Septic patients should be aggressively resuscitated with hypotension (mean arterial pressure < 65 mm Hg) or an elevated lactate (>4 mmol/L) with a balanced crystalloid solution.
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Fluid resuscitation after the initial bolus should be guided by assessment of intravascular volume.
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Norepinephrine is the vasopressor of choice in septic shock.
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Septic patients are resource intensive; initial one-to-one nursing care improves adherence to guidelines.
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The ultimate disposition of septic patients in a CED (ICU vs transfer) should be considered early in their care so as not to delay definitive care.
Sepsis in low- and middle-income countries
Accurate sepsis incidence and mortality data are still lacking in LMICs. A Brazilian study showed an incidence of sepsis and septic shock of 61.4 and 30 per 1000 patient-days, respectively, with mortality rates from sepsis of 35% and 52% from septic shock. This finding was similar to that of a report from Zambia that showed a sepsis-related mortality rate of approximately 55%. Results can vary widely, however, as a study from Asian ICUs showed rates of sepsis ranging from 10% in Bangladesh to 54% in Nepal. The true incidence of sepsis in LMICs is unknown, as a recent review found no population-level estimates from LMICs.
In the coming sections, the great disparity in the ability to diagnose and treat sepsis between countries and within the borders of a single country is explored. An example of this disparity is the availability of ICU beds. In the United States there are 20 ICU beds per 100,000 population; this number decreases to 8.9 in South Africa, 3.9 in China, and 1.6 in Sri Lanka. Underlying pathologic and comorbid conditions can also vary widely. LMICs face an increased burden of disease from human immunodeficiency virus (HIV), malaria, and tuberculosis that complicate treatment. This variation in underlying conditions and comorbidity is believed to be partly responsible for the conflicting results of studies attempting to bring early, goal-directed therapy protocols to LMICs.
Case Studies
A limited amount of research suggests that utilization of sepsis bundles and protocols in LMICs is associated with improved outcomes. This section looks at a few specific studies that have promising results. Similar to related research in HICs, however, these success stories are mostly found in academic settings, limiting the generalizability of their results.
China
Wang and colleagues conducted a study looking at mortality before and after implementation of a protocol designed to identify and treat severe sepsis and septic shock. They included patients based on the more nuanced definitions of severe sepsis (eg, end-organ dysfunction) and septic shock (eg, persistent hypotension or lactate ≥4) and had a protocol based on the 2004 version of the SSC guidelines broken down into a resuscitation bundle and management bundle. The results are summarized in Table 1 . These results show that although full compliance with the protocol was not remarkably high (8.5%), even this modest adherence may have led to significantly better outcomes in mortality and various performance indicators. However, also notable was the large increase in early antibiotic delivery and aggressive fluid administration, which may explain the outcomes.
| Preprotocol | Postprotocol | |
|---|---|---|
| Patients | 78 | 117 |
| % Severe sepsis | 70.5% | 69.2% |
| % Septic shock | 29.5% | 30.8% |
| In-hospital mortality | 35 (44.8%) | 37 (31.6%) a |
| % ICU | 39% | 27% |
| % Boarders | 54% | 43% |
| % Compliance with bundle | 1.3% | 8.5% a |
| % Fluid bolus (20 mL/kg) | 27% | 82.9% a |
| % Antibiotics <3 h of triage | 25.6% | 69.2% a |
In addition to these findings, the investigators identified numerous barriers to completing the protocol. They found that there was often a delay in antibiotic administration, as a representative of the patient’s family had to go to the pharmacy to purchase antibiotics and bring them back to the patient. In addition, nurses would simply carry out orders in the order in which they were written; thus, if antibiotics were at the bottom of the orders, they would be given last. These types of delays are common in LMICs (and to a lesser extent in US CEDs) but are examples of barriers that could be overcome with increased awareness and education.
Brazil
A report in 2003 found that despite spending more than $8 billion on hospital care for patients, mortality from sepsis was 56% in Brazil. This rate was notably higher than the 45% figure for other developing nations surveyed in the study. The implementation of the SSC guidelines in Brazil is under the direction of the Latin American Sepsis Institute. The Latin American Sepsis Institute uses a combination of education campaigns, manuals, and data collection to coordinate care across Latin America and has resulted in widespread use of sepsis protocols at many hospitals in Brazil. Literature coming out of this work has shown that increased awareness toward diagnosing sepsis and early administration of fluids and antibiotics can lead to reduction in sepsis-related mortality.
A study by Westphal and colleagues looked at the difference in diagnosis of sepsis when applying the SSC guidelines diagnostic criteria to all patients rather than just those already with an infection. The study took place at 2 hospitals in southern Brazil with “average to advanced levels of care.” They used the expanded definition of severe sepsis (eg, end-organ dysfunction) and usual definition of septic shock (eg, hypotension, elevated lactate). The protocol consisted of nursing technicians screening patients for criteria that would qualify for either severe sepsis or septic shock. Then, a ward nurse would review the case and consult a physician for treatment if he or she thought the patient met criteria. This protocol took place in EDs, ICUs, and the wards. The initial phase only screened patients with infection, whereas the intervention phase screened all patients. Although overall compliance did not significantly change, the increased screening led to significant improvements in time to diagnosis and mortality. The relevant results are summarized in Table 2 .
Related posts:
Severe Sepsis Care in the Emergency Department
An Introduction to the Most Complex Disease in Emergency Medicine
End Points of Sepsis Resuscitation
The Past, Present, and Future of the Centers for Medicare and Medicaid Services Quality Measure SEP-1
Appropriate Antibiotic Therapy
Prehospital Sepsis Care
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