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Integrating sepsis management recommendations into clinical care guidelines for district hospitals in resource-limited settings: the necessity to augment new guidelines with future research

  • Shevin T Jacob1Email author,
  • Matthew Lim2,
  • Patrick Banura3,
  • Satish Bhagwanjee4,
  • Julian Bion5,
  • Allen C Cheng6,
  • Hillary Cohen7,
  • Jeremy Farrar8,
  • Sandy Gove9,
  • Philip Hopewell10,
  • Christopher C Moore11,
  • Cathy Roth12 and
  • T Eoin West1
BMC Medicine201311:107

https://doi.org/10.1186/1741-7015-11-107

©  Jacob et al.; licensee BioMed Central Ltd. 2013

Received: 16 January 2013

Accepted: 18 March 2013

Published: 18 April 2013

Open Peer Review reports

Abstract

Several factors contribute to the high mortality attributed to severe infections in resource-limited settings. While improvements in survival and processes of care have been made in high-income settings among patients with severe conditions, such as sepsis, guidelines necessary for achieving these improvements may lack applicability or have not been tested in resource-limited settings. The World Health Organization’s recent publication of the Integrated Management of Adolescent and Adult Illness District Clinician Manual provides details on how to optimize management of severely ill, hospitalized patients in such settings, including specific guidance on the management of patients with septic shock and respiratory failure without shock. This manuscript provides the context, process and underpinnings of these sepsis guidelines. In light of the current deficits in care and the limitations associated with these guidelines, the authors propose implementing these standardized best practice guidelines while using them as a foundation for sepsis research undertaken in, and directly relevant to, resource-limited settings.

Keywords

SepsisResource-limited settingSevere illnessGuidelines

Background

To provide guidance on a comprehensive approach to the management of children and adult patients with common diseases and conditions in resource-limited settings, the World Health Organization (WHO) has coordinated the development of a set of integrated management tools. These tools, comprised of guidelines and health worker training modules, include the Integrated Management of Childhood Illness, the Integrated Management of Pregnancy and Childbirth, and the Integrated Management of Adolescent and Adult Illness (IMAI). Many of these tools have been widely disseminated globally [1]. In July 2011, the WHO approved the publication of the most recent addition to the integrated management series, the IMAI District Clinician Manual (DCM). This document, just released on-line and in print, is a two-volume publication providing guidance on the care of hospitalized adult patients in district hospitals from resource-limited settings [2].

In resource-limited settings, management of severely ill patients is particularly challenging due to a difficult balance between a high caseload of patients and the correspondingly low supply of necessary medical equipment and human resources [3, 4]. Public health crises such as the 2009 H1N1 influenza pandemic have reinforced concerns about the potential for a rapid overwhelming of the global health system’s capacity to manage patients with severe acute illness, particularly in settings with limited resources [5]. To address this challenge, the DCM emphasizes a practical and systematic approach to triage and management of all patients presenting to the hospital in resource-limited settings with an acute illness, including those who are critically ill.

Infectious diseases have a disproportionate impact on populations in low and middle income countries and cause correspondingly high mortality rates [6, 7]. Regardless of the etiology, one of the most common pathways contributing to this mortality is the ‘sepsis syndrome’, defined by the presence of both infection and a systemic inflammatory response. Further along the severity spectrum of this syndrome, severe sepsis and septic shock can occur with increasing lethality resulting from progression to end-organ damage and refractory hypotension [8]. While it is poorly quantified, the global burden of sepsis is undoubtedly massive. Extrapolating from North American data, some 15 to 20 million cases of severe sepsis among adults occur worldwide each year, half of which may be fatal [9]. Available data on sepsis management of adults in resource-limited settings suggest that this high mortality is associated with ineffective management including delayed and improper empiric antimicrobial therapy as well as sub-optimal fluid resuscitation [10, 11]. Thus, attention to reducing the mortality from sepsis by focusing on improved management in these settings is urgently needed.

Given the importance of this condition, in 2009 the WHO convened an international group of experts to review the current management of sepsis and to identify an evidence-based strategy and approach for sepsis management in resource-limited settings. These guidelines were subsequently included in the IMAI DCM as a framework for the management of severe acute illness in adults. The purpose of this article is to delineate the barriers to optimal sepsis management in resource-limited settings, describe the approach used to develop the IMAI DCM sepsis guidelines and their inherent limitations, identify the knowledge gaps and highlight key questions that must be answered to further inform and refine best practice for the management of sepsis in these settings.

Current standard of care of sepsis in high-resource settings

Studies conducted in high-income countries have suggested a benefit from early sepsis identification coupled with targeted interventions in the management of patients with severe sepsis. These interventions include rapid administration of appropriate antimicrobial therapy, additional source control of infection as needed, and optimization of tissue perfusion using fluids, vasopressors and inotropes, and red blood cell transfusions. These initial actions are accompanied by support of failing organs and appropriate efforts to minimize complications. Protocol-driven strategies are the basis for the best practice guidelines for sepsis care promulgated by the International Surviving Sepsis Campaign [12]. Several independent, multi-site studies from middle and high income countries have demonstrated improved survival in parallel with improvements in compliance with aggregate best practice guidance (‘sepsis bundles’) [12–22]. Importantly, the results of studies re-evaluating the efficacy of certain sepsis bundle components (for example, activated protein C, tight glucose control and low-dose steroids) has led to revision, and sometimes removal, of these components in more recent iterations of the guidelines [23]. Thus, in an effort to independently evaluate goal-directed resuscitation in adults with septic shock, three parallel randomized-controlled multicenter trials in Australia, the USA and the UK are underway [24–26].

Applicability of existing sepsis guidelines to resource-limited settings

While there is some evidence to support the feasibility of implementing modified sepsis management guidelines in resource-limited settings [27], substantial health system and resource challenges impede the translation of current best practice guidelines in these environments [28–31]. For example, variable access and long distances to hospitals contribute to severely ill patients presenting to the health system. In addition, triage capacity is often absent in district hospitals, leading to further delays in recognizing ill patients and initiating treatment. Once recognized, a lack of effective antimicrobials, oxygen and intravenous fluids may further impair provision of optimal sepsis care. Moreover, human resources are often scarce with respect to both quantity and expertise, thus precluding the labor-intensive iterative approach that characterizes sepsis management in high resource settings.

Identifying which should be the priority interventions for sepsis management in a resource-limited setting is a further challenge. While evidence exists for the benefit of prompt and appropriate antimicrobial therapy, answering questions regarding the utility of other therapies commonly available in high-resource settings is difficult. For example, are intravenous fluid boluses safe in the absence of close patient monitoring and respiratory support equipment? Are central venous catheters beneficial for guiding volume resuscitation in a resource-limited setting when weighed against the attendant risks of mechanical complications and infection? Given global efforts to improve oxygen monitoring capacity and supply, what level of oxygen should be targeted in septic patients? Furthermore, it is not known if (or which) isolated interventions in sepsis, unbundled from the packages of sepsis care that have been adopted in high resource hospitals, may still result in net benefit.

The etiologies of sepsis in many resource-limited environments differ from high resource settings or have not been well described. Bacteraemia studies implicate a wide range of pathogens [10, 32–34]. Many other organisms including Plasmodium falciparum, dengue virus, influenza, Mycobacterium tuberculosis, Cryptococcus neoformans and Rickettsia species may cause severe clinical illness that cannot be easily distinguished from typical bacterial sepsis [10, 35–39]. In addition, immune suppression from HIV is an important risk factor for adult sepsis in places where HIV prevalence is high [10]. Thus, clinical trials of sepsis therapies conducted in high-resource settings and targeting mostly bacterial infection may not be generalizable to resource-limited settings. This issue is further compounded by the dearth of diagnostic capacity to identify the specific etiologies of sepsis and to determine antimicrobial susceptibility in most district hospitals. Consequently, there is little empirically-derived local or regional data to guide hospital procurement and clinician selection of appropriate antimicrobial treatment.

Finally, populations in resource-limited settings are likely to differ from those in high-resource settings in a variety of ways. Nutritional status, co-morbidities, health seeking behaviors, access to health care, and use of over-the-counter and sub-standard or counterfeit antimicrobials may all influence the mode of presentation that can impact clinical outcome. Thus, management strategies developed in high-resource populations may not be directly applicable in resource-limited populations.

An excellent example of the risk of extrapolating principles of sepsis care across settings was demonstrated by the recent FEAST trial [40]. This large trial involving more than 3,000 African children with severe acute infections showed that children receiving fluid boluses had a higher mortality than children receiving no fluid bolus. This unexpected finding, which arguably may be more generalizable to adults in the same setting than findings from studies performed in developed countries, suggests that validation studies are required to establish the benefit of the IMAI approach which is largely based on lower level evidence. Furthermore, mortality among all patients enrolled in the FEAST trial was strikingly lower (9.4%) than in severely ill children enrolled in previous studies from similar settings (28.2%) [41]. This effect may be attributable to targeted training of all health staff on triage and monitoring prior to commencement of the study and supports the importance of emergency care training of health workers.

A sepsis management pathway in resource-limited settings

Starting in April 2009, a working group was convened by the WHO to develop sepsis management guidelines in resource-limited settings. The group comprised 18 international experts from five continents trained in internal medicine, emergency medicine, anesthetics, critical care, infectious disease and pulmonology. Three face-to-face meetings (one co-incident with the IMAI DCM pulmonary and emergency expert groups meeting), evidence review and numerous email consultations were held. Development of the guidelines occurred by consensus and recommendations were not necessarily restricted by the lack of a high quality evidence base. These efforts eventually dovetailed with the IMAI DCM development process (in development since 2006) and in November 2009, the sepsis guidelines were adapted for management of severely ill patients during the H1N1 influenza pandemic [42]. In July 2011, prior to its final approval for publication, the WHO held a three-day external review of the IMAI DCM which includes the sepsis guidelines for resource-limited settings.

The guidelines take into consideration potential resource constraints, acknowledging that much of the world does not have access to advanced diagnostics or resuscitative techniques. They provide instruction on sepsis management in resource-limited environments throughout a patient’s hospitalization course with emphasis on the first 2 hours (Figure 1a), 2 to 6 hours (Figure 1b), 6 to 24 hours (Figure 1c) and post-resuscitation periods (Figure 1d) [2]. The guidelines call for the early recognition of two of the most important indicators of organ dysfunction in sepsis: hypotension and acute respiratory distress. Key management principles reiterated through the guidelines include early recognition, treating infection early and broadly while establishing source control and fixing physiologic aberrations by optimizing tissue perfusion with judicious fluids and oxygen. In addition, the guidelines emphasize regular and frequent monitoring of the patient's response to treatment and a plan for appropriate action based on changes in clinical status. In light of the risk of volume overloading patients with possible acute lung injury/acute respiratory distress syndrome, the guidelines specify more conservative fluids for such patients (1 ml/kg/hour intravenously or orally) and other appropriate modifications in the resuscitation strategy. Further guidance on the management of conditions which may deviate from these guidelines is provided in the DCM, including a more conservative fluid management strategy for dengue; careful attention to possible development of fluid overload/pulmonary edema in severe malaria; specific antimicrobial recommendations for malaria, tuberculosis, maternal sepsis-related conditions (for example, amnionitis, post-partum sepsis and septic abortion) and certain viral hemorrhagic fevers (such as Lassa fever).
Figure 1

Guidelines for the management of septic shock and severe respiratory distress without shock in resource-limited settings. (a) Algorithm for the first 2 hours of hospitalization. (b) Algorithm for hours 2 to 6 after hospitalization. (c) Algorithm for hours 6 to 24 after hospitalization. (d) Algorithm for the post-resuscitation period. (Permission granted by the World Health Organization for reproducing the contents of this figure from the IMAI District Clinician Manual [2].)

Most importantly, these guidelines do not exist within a vacuum. They are situated within a larger context of expedited assessment, triage and immediate intervention, using algorithms that rapidly differentiate life threatening emergency conditions from those that require less urgent care. Thus, all patients are similarly triaged by assessing whether they exhibit emergency signs related to the airway and breathing (obstruction, central cyanosis, severe respiratory distress), circulation (weak or fast pulse, capillary refill longer than three seconds, heavy bleeding or severe trauma), altered level of consciousness or convulsions or pain from a life-threatening cause [43]. The sepsis management algorithm is only triggered once underlying infection is suspected and other causes of circulatory impairment have been excluded. To avoid inappropriate guideline implementation, emphasis is placed on supporting clinical reasoning and use of differential diagnosis tables. Ultimately, patients are treated for the most likely and urgent disease syndromes without premature exclusion of alternative diagnoses, using methods and resources available even in resource-limited settings.

Successful sepsis algorithm implementation depends, above all, on improving health worker capacity to manage severely ill patients through effective training to use the algorithm as well as constant revision through new research. Accordingly, a district hospital training program based on the DCM to improve the capacity for triage and management of severe acute illness focused on septic shock and respiratory distress has been piloted by the WHO in Uganda, Malawi, Ethiopia and Rwanda. In addition to the principles of triage and management, the training also emphasizes the importance of achieving clinical management benchmarks using targeted clinical performance measures based on reasonable standards of care in resource-limited settings. Also, simplified data collection instruments that allow bedside clinical and laboratory documentation are introduced to inform therapeutic adjustments when necessary and facilitate long-term quality improvement and clinical research efforts. A similar training program has already been shown to reduce mortality in pediatric patients in a resource-limited setting [44].

Limitations, knowledge gaps and future directions

The proposed sepsis pathway is based on a sound physiological rationale and is derived from the best evidence currently available pertinent to the care of adults with sepsis, most of which was developed in high resource settings. A subsequent independent evidence-based review of sepsis management in resource-limited settings arrived at very similar recommendations and confirmed that evidence from resource-limited settings is deplorably scarce [45]. Despite the lack of empirically derived data in resource-limited settings, we propose that it is ethically acceptable to provide guidelines to health care providers that are based on the application of sound physiological principles and the best available current evidence. It is also essential, however, that research be undertaken to evaluate areas of uncertainty in the guidelines (for example, determining the safest and most efficacious volume of fluid resuscitation for improving sepsis survival) and to validate the effectiveness of the guidelines’ performance in appropriate settings with modification of the guidelines based on these findings. This process of validating and revising guidelines mirrors the approach used in high resource settings by the Surviving Sepsis Campaign [46]. Given the unique challenges of infrastructure and human capacity limitations and the substantial knowledge gaps specific to resource-limited settings, key issues for further investigation include:
  1. 1.

    Evaluating the efficacy and effectiveness of training in the proposed management pathway for improving patient outcomes and health care worker performance, particularly in patient populations and settings where invasive monitoring and extensive laboratory investigations are absent.

     
  2. 2.

    Improving the recognition and defining the natural history of sepsis caused by organisms endemic in developing countries, while refining management of those clinical syndromes where a pathogen-specific guideline may be superior. Further clinical research is necessary to determine where and how the proposed guidelines can complement existing disease-specific recommendations and whether specific components require further evaluation.

     
  3. 3.

    Through the evaluation of severity scoring systems and differing clinical definitions, defining groups for which early intervention may be either particularly beneficial or futile.

     
  4. 4.

    Determining the potential benefit of adjunctive treatments (such as non-invasive ventilation) and interventions that may augment current care (for example, the use of oral fluids, the use of ultrasound to guide amount of fluid resuscitation, the role of early feeding and micronutrient supplementation and the training of patient relatives as clinical care attendants).

     
  5. 5.

    Conducting relative cost-benefit analyses addressing supply issues and resource utilization for basic treatments, such as oxygen, intravenous fluids and antimicrobials can aid health facilities in determining how to prioritize resources required for sepsis management.

     
  6. 6.

    Tailoring treatment more effectively by enhancing on-site diagnosis, through either improved basic microbiology services, expanded sentinel surveillance microbiologic laboratory sites or the use of novel rapid diagnostic tests comprising assays which can identify sepsis etiology and/or provide prognostic information at the point of care.

     

Conclusion

Current evidence suggests that the mortality and morbidity of severe sepsis can be improved by effective clinical interventions applied in a timely and systematic manner. In resource-limited settings where the burden of disease is highest but least well studied, there remain many barriers to the adoption of such practices. The essential elements of care of critically ill patients in resource-limited settings are a triage system that identifies critical illness quickly, appropriate protocols for managing common medical emergencies, the availability of requisite interventions, targeted training of providers in critical care principles, and a data collection and quality management system to monitor implementation and impact. This sepsis management pathway for resource-limited settings, a subset of the larger severe illness recognition and management algorithms within the IMAI District Clinician Manual, adheres to these principles and provides an essential first step in improving outcomes. It should be feasible to design and implement a package comprising these elements adapted for any setting but in order to ensure that such guidelines fulfill their potential for saving lives, a robust global effort championing training and research in the management of acute severe illnesses, such as sepsis, in resource-limited settings is essential.

Authors’ information

All authors were part of World Health Organization working groups to develop guidelines for the management of severe sepsis in resource-limited settings. In their previous roles at the World Health Organization, CR and ML led the activities of this working group. During the development of these sepsis guidelines and the District Clinician Manual, SG was the team leader for the IMAI program in the HIV department at the World Health Organization. STJ, HC and SG were overall technical editors for the IMAI District Clinician Manual.

STJ and ML are co-first authors.

Abbreviations

IMAI: 

Integrated management of adolescent and adult illness

DCM: 

District Clinician Manual

WHO: 

World health organization.

Declarations

Acknowledgements

We would like to thank all members of the World Health Organization Sepsis Working Group for their contributions to the development of the sepsis guidelines and all contributors to the larger two-volume IMAI DCM. This work was funded by the World Health Organization and by USAID contributions for IMAI through the WHO HIV Department.

Authors’ Affiliations

(1)
International Respiratory and Severe Illness Center (INTERSECT), Department of Medicine, University of Washington, Seattle, USA
(2)
Department of Health and Human Services, Office of Global Affairs, Washington, USA
(3)
Community Health Department, Masaka Regional Referral Hospital, Masaka, Uganda
(4)
Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, USA
(5)
University Department Anaesthesia & Intensive Care Medicine, N5, Queen Elizabeth Hospital (old site), Edgbaston, UK
(6)
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
(7)
Department of Emergency Medicine, Maimonides Medical Center, Brooklyn, USA
(8)
Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
(9)
IMAI-IMCI Alliance, San Francisco, USA
(10)
Division of Pulmonary and Critical Care Medicine, Department of Medicine, San Francisco General Hospital, University of California, San Francisco, USA
(11)
Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, USA
(12)
Health Security and Environment Department, World Health Organization, Geneva, 27, Switzerland

References

  1. HIV/AIDS: Programmes and projects: http://www.who.int/hiv/topics/capacity/en/index.html.
  2. IMAI District Clinician Manual: Hospital Care for Adolescents and Adults. Guidelines for the Management of Illnesses with Limited Resources. 2011, Geneva: World Health OrganizationGoogle Scholar
  3. Dunser MW, Baelani I, Ganbold L: A review and analysis of intensive care medicine in the least developed countries. Crit Care Med. 2006, 34: 1234-1242. 10.1097/01.CCM.0000208360.70835.87.View ArticlePubMedGoogle Scholar
  4. Riviello ED, Letchford S, Achieng L, Newton MW: Critical care in resource-poor settings: lessons learned and future directions. Crit Care Med. 2011, 39: 860-867. 10.1097/CCM.0b013e318206d6d5.View ArticlePubMedGoogle Scholar
  5. Fisher D, Hui DS, Gao Z, Lee C, Oh MD, Cao B, Hien TT, Patlovich K, Farrar J: Pandemic response lessons from influenza H1N1 2009 in Asia. Respirology. 2011, 16: 876-882. 10.1111/j.1440-1843.2011.02003.x.View ArticlePubMedGoogle Scholar
  6. Cheng AC, West TE, Limmathurotsakul D, Peacock SJ: Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLoS Med. 2008, 5: e175-10.1371/journal.pmed.0050175.View ArticlePubMedPubMed CentralGoogle Scholar
  7. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M: Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2013, 380: 2095-2128.View ArticleGoogle Scholar
  8. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Ramsay G: SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Crit Care Med. 2001, 2003 (31): 1250-1256.Google Scholar
  9. Adhikari NK, Fowler RA, Bhagwanjee S, Rubenfeld GD: Critical care and the global burden of critical illness in adults. Lancet. 2010, 376: 1339-1346. 10.1016/S0140-6736(10)60446-1.View ArticlePubMedGoogle Scholar
  10. Jacob ST, Moore CC, Banura P, Pinkerton R, Meya D, Opendi P, Reynolds SJ, Kenya-Mugisha N, Mayanja-Kizza H, Scheld WM: Severe sepsis in two Ugandan hospitals: a prospective observational study of management and outcomes in a predominantly HIV-1 infected population. PLoS One. 2009, 4: e7782-10.1371/journal.pone.0007782.View ArticlePubMedPubMed CentralGoogle Scholar
  11. Jacob ST, Banura P, Baeten JM, Moore CC, Meya D, Nakiyingi L, Burke R, Horton CL, Iga B, Wald A, Reynolds SJ, Mayanja-Kizza H, Scheld WM, Promoting Resource-Limited 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. 10.1097/CCM.0b013e31824e65d7.View ArticlePubMedPubMed CentralGoogle Scholar
  12. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K, Angus DC, Brun-Buisson C, Beale R, Calandra T, Dhainaut JF, Gerlach H, Harvey M, Marini JJ, Marshall J, Ranieri M, Ramsay G, Sevransky J, Thompson BT, Townsend S, Vender JS, Zimmerman JL, Vincent JL: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008, 36: 296-327. 10.1097/01.CCM.0000298158.12101.41.View ArticlePubMedGoogle Scholar
  13. Daniels R, Nutbeam T, McNamara G, Galvin C: The sepsis six and the severe sepsis resuscitation bundle: a prospective observational cohort study. Emerg Med J. 2011, 28: 507-512. 10.1136/emj.2010.095067.View ArticlePubMedGoogle Scholar
  14. Ferrer R, Artigas A, Levy MM, Blanco J, Gonzalez-Diaz G, Garnacho-Montero J, Ibanez J, Palencia E, Quintana M, de la Torre-Prados MV: Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008, 299: 2294-2303. 10.1001/jama.299.19.2294.View ArticlePubMedGoogle Scholar
  15. Lefrant JY, Muller L, Raillard A, Jung B, Beaudroit L, Favier L, Masson B, Dingemans G, Thevenot F, Selcer D, Jonquet O, Capdevila X, Fabbro-Peray P, Jaber S, Sepsi d'Oc study Group in the AzuRéa Group: Reduction of the severe sepsis or septic shock associated mortality by reinforcement of the recommendations bundle: a multicenter study. Ann Fr Anesth Reanim. 2010, 29: 621-628. 10.1016/j.annfar.2010.04.007.View ArticlePubMedGoogle Scholar
  16. Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, Schorr C, Artigas A, Ramsay G, Beale R, Parker MM, Gerlach H, Reinhart K, Silva E, Harvey M, Regan S, Angus DC, Surviving Sepsis Campaign: The surviving sepsis campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Crit Care Med. 2010, 38: 367-374. 10.1097/CCM.0b013e3181cb0cdc.View ArticlePubMedGoogle Scholar
  17. Nguyen HB, Kuan WS, Batech M, Shrikhande P, Mahadevan M, Li CH, Ray S, Dengel A: Outcome effectiveness of the severe sepsis resuscitation bundle with addition of lactate clearance as a bundle item: a multi-national evaluation. Crit Care. 2011, 15: R229-10.1186/cc10469.View ArticlePubMedPubMed CentralGoogle Scholar
  18. Patel GW, Roderman N, Gehring H, Saad J, Bartek W: Assessing the effect of the surviving sepsis campaign treatment guidelines on clinical outcomes in a community hospital. Ann Pharmacother. 2010, 44: 1733-1738. 10.1345/aph.1P251.View ArticlePubMedGoogle Scholar
  19. Shiramizo SC, Marra AR, Durao MS, Paes AT, Edmond MB, Pavao dos Santos OF: Decreasing mortality in severe sepsis and septic shock patients by implementing a sepsis bundle in a hospital setting. PloS one. 2011, 6: e26790-10.1371/journal.pone.0026790.View ArticlePubMedPubMed CentralGoogle Scholar
  20. Tromp M, Tjan DH, van Zanten AR, Gielen-Wijffels SE, Goekoop GJ, van den Boogaard M, Wallenborg CM, Biemond-Moeniralam HS, Pickkers P: The effects of implementation of the surviving sepsis campaign in the Netherlands. Neth J Med. 2011, 69: 292-298.PubMedGoogle Scholar
  21. Westphal GA, Koenig A, Caldeira Filho M, Feijo J, de Oliveira LT, Nunes F, Fujiwara K, Martins SF, Roman Goncalves AR: Reduced mortality after the implementation of a protocol for the early detection of severe sepsis. J Crit Care. 2011, 26: 76-81. 10.1016/j.jcrc.2010.08.001.View ArticlePubMedGoogle Scholar
  22. Phua J, Koh Y, Du B, Tang YQ, Divatia JV, Tan CC, Gomersall CD, Faruq MO, Shrestha BR, Gia Binh N, Arabi YM, Salahuddin N, Wahyuprajitno B, Tu ML, Wahab AY, Hameed AA, Nishimura M, Procyshyn M, Chan YH, MOSAICS Study Group: Management of severe sepsis in patients admitted to Asian intensive care units: prospective cohort study. BMJ. 2011, 342: d3245-10.1136/bmj.d3245.View ArticlePubMedPubMed CentralGoogle Scholar
  23. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R, Osborn TM, Nunnally ME, Townsend SR, Reinhart K, Kleinpell RM, Angus DC, Deutschman CS, Machado FR, Rubenfeld GD, Webb SA, Beale RJ, Vincent JL, Moreno R, Surviving Sepsis Campaign Guidelines Committee including the Pediatric Subgroup: Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013, 41: 580-637. 10.1097/CCM.0b013e31827e83af.View ArticlePubMedGoogle Scholar
  24. Protocolized Care for Early Septic Shock (ProCESS): http://clinicaltrials.gov/ct2/show/NCT00510835.
  25. Australasian Resuscitation in Sepsis Evaluation (ARISE-RCT): http://www.anzics.com.au/ctg/current-research/67-arise.
  26. Protocolised Management in Sepsis (ProMISe): http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=9820.
  27. Mahavanakul W, Nickerson EK, Srisomang P, Teparrukkul P, Lorvinitnun P, Wongyingsinn M, Chierakul W, Hongsuwan M, West TE, Day NP, Limmathurotsakul D, Peacock SJ: Feasibility of modified surviving sepsis campaign guidelines in a resource-restricted setting based on a cohort study of severe S. aureus sepsis. PLoS One. 2012, 7: e29858-10.1371/journal.pone.0029858.View ArticlePubMedPubMed CentralGoogle Scholar
  28. Baelani I, Jochberger S, Laimer T, Otieno D, Kabutu J, Wilson I, Baker T, Dunser MW: Availability of critical care resources to treat patients with severe sepsis or septic shock in Africa: a self-reported, continent-wide survey of anaesthesia providers. Crit Care. 2011, 15: R10-10.1186/cc9410.View ArticlePubMedPubMed CentralGoogle Scholar
  29. Baker T: Critical care in low-income countries. Trop Med Int Health. 2009, 14: 143-148. 10.1111/j.1365-3156.2008.02202.x.View ArticlePubMedGoogle Scholar
  30. Bataar O, Lundeg G, Tsenddorj G, Jochberger S, Grander W, Baelani I, Wilson I, Baker T, Dunser MW: Nationwide survey on resource availability for implementing current sepsis guidelines in Mongolia. Bull World Health Organ. 2010, 88: 839-846. 10.2471/BLT.10.077073.View ArticlePubMedPubMed CentralGoogle Scholar
  31. Jacob ST, West TE, Banura P: Fitting a square peg into a round hole: are the current surviving sepsis campaign guidelines feasible for Africa?. Crit Care. 2011, 15: 117-10.1186/cc9981.View ArticlePubMedPubMed CentralGoogle Scholar
  32. Reddy EA, Shaw AV, Crump JA: Community-acquired bloodstream infections in Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2010, 10: 417-432. 10.1016/S1473-3099(10)70072-4.View ArticlePubMedPubMed CentralGoogle Scholar
  33. Vray M, Germani Y, Chan S, Duc NH, Sar B, Sarr FD, Bercion R, Rahalison L, Maynard M, L'Her P, Chartier L, Mayaud C: Clinical features and etiology of pneumonia in acid-fast bacillus sputum smear-negative HIV-infected patients hospitalized in Asia and Africa. AIDS. 2008, 22: 1323-1332. 10.1097/QAD.0b013e3282fdf8bf.View ArticlePubMedGoogle Scholar
  34. Watanabe H, Asoh N, Kobayashi S, Watanabe K, Oishi K, Kositsakulchai W, Sanchai T, Khantawa B, Tharavichitkul P, Sirisanthana T, Sirisanthana T, Nagatake T: Clinical and microbiological characteristics of community-acquired pneumonia among human immunodeficiency virus-infected patients in northern Thailand. J Infect Chemother. 2008, 14: 105-109. 10.1007/s10156-007-0577-9.View ArticlePubMedGoogle Scholar
  35. Bruneel F, Gachot B, Timsit JF, Wolff M, Bedos JP, Regnier B, Vachon F: Shock complicating severe falciparum malaria in European adults. Intensive Care Med. 1997, 23: 698-701. 10.1007/s001340050396.View ArticlePubMedGoogle Scholar
  36. Chipp E, Digby S: Rickettsia: an unusual cause of sepsis in the emergency department. Emerg Med J. 2006, 23: e60-10.1136/emj.2006.040113.View ArticlePubMedPubMed CentralGoogle Scholar
  37. Ho YC, Wang JL, Wang JT, Wu UI, Chang CW, Wu HS, Chen CH, Chuang YM, Chang SC: Prognostic factors for fatal adult influenza pneumonia. J Infect. 2009, 58: 439-445. 10.1016/j.jinf.2009.03.007.View ArticlePubMedGoogle Scholar
  38. Lewis DK, Peters RP, Schijffelen MJ, Joaki GR, Walsh AL, Kublin JG, Kumwenda J, Kampondeni S, Molyneux ME, Zijlstra EE: Clinical indicators of mycobacteraemia in adults admitted to hospital in Blantyre, Malawi. Int J Tuberc Lung Dis. 2002, 6: 1067-1074.PubMedGoogle Scholar
  39. Rigau-Perez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV: Dengue and dengue haemorrhagic fever. Lancet. 1998, 352: 971-977. 10.1016/S0140-6736(97)12483-7.View ArticlePubMedGoogle Scholar
  40. Maitland K, Kiguli S, Opoka RO, Engoru C, Olupot-Olupot P, Akech SO, Nyeko R, Mtove G, Reyburn H, Lang T, Brent B, Evans JA, Tibenderana JK, Crawley J, Russell EC, Levin M, Babiker AG, Gibb DM, FEAST Trial Group: Mortality after fluid bolus in African children with severe infection. N Engl J Med. 2011, 364: 2483-2495. 10.1056/NEJMoa1101549.View ArticlePubMedGoogle Scholar
  41. Berkley JA, Lowe BS, Mwangi I, Williams T, Bauni E, Mwarumba S, Ngetsa C, Slack MP, Njenga S, Hart CA, Maitland K, English M, Marsh K, Scott JA: Bacteremia among children admitted to a rural hospital in Kenya. N Engl J Med. 2005, 352: 39-47. 10.1056/NEJMoa040275.View ArticlePubMedGoogle Scholar
  42. World Health Organization: Clinical management of adult patients with complications of pandemic influenza A (H1N1). 2009, http://whqlibdoc.who.int/publications/2010/9789241599610_eng.pdf, : emergency guidelines for the management of patients with severe respiratory distress and shock in district hospitals in limited-resource settings.
  43. World Health Organization: Influenza: Programmes and projects-Clinical management. http://www.who.int/influenza/patient_care/clinical/en/.
  44. Molyneux E, Ahmad S, Robertson A: Improved triage and emergency care for children reduces inpatient mortality in a resource-constrained setting. Bull World Health Organ. 2006, 84: 314-319.View ArticlePubMedPubMed CentralGoogle Scholar
  45. Dunser MW, Festic E, Dondorp A, Kissoon N, Ganbat T, Kwizera A, Haniffa R, Baker T, Schultz MJ: Recommendations for sepsis management in resource-limited settings. Intensive Care Med. 2012, 38: 557-574. 10.1007/s00134-012-2468-5.View ArticlePubMedPubMed CentralGoogle Scholar
  46. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerman JL, Vincent JL, Levy MM: Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med. 2004, 30: 536-555. 10.1007/s00134-004-2210-z.View ArticlePubMedGoogle Scholar

    47. Pre-publication history

    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1741-7015/11/107/prepub

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© Jacob et al.; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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