2.1 Introduction

In 2014, the “Global Intensive Care Working Group” of the “European Society of Intensive Care Medicine” (ESICM) and the “Mahidol Oxford Tropical Medicine Research Unit” (MORU) in Bangkok, Thailand, decided to refine and rewrite the guidelines for sepsis treatment in resource-limited settings as published in 2012 [1]. This chapter describes the development of eight sets of recommendations for care of septic patients in resource-limited settings as published in Intensive Care Medicine [2,3,4,5,6,7,8] and the Transactions of Royal Society of Tropical Medicine and Hygiene [9] in 2016 and 2017.

2.2 Heads and Subheads

The chairmen of the newly formed “Sepsis in Resource-Limited Settings” guidelines group, Marcus J. Schultz, Martin W. Dünser, and Arjen M. Dondorp, contacted potential subgroup chairs (Table 2.1) for the development of eight sets of recommendations focusing on (1) intensive care unit (ICU) organization and structure, (2) sepsis recognition, (3) infection management, (4) tropical sepsis, (5) hemodynamic monitoring and support, (6) ventilatory support, (7) general supportive care, and (8) pediatric sepsis. The selection of subgroup chairs was based on interest in specific aspects of sepsis and hands-on experience in ICUs in resource-limited settings. In total, three subgroup chairs per set of recommendations were contacted. Marcus J. Schultz, Martin W. Dünser, and Arjen M. Dondorp set out a protocol for the appraisal of various aspects within each set of recommendations and discussed this with the subgroup chairs.

Table 2.1 Group chairs, subgroup chairs, and subgroup members
Full size table

2.3 Other Subgroup Members

The chairs of each subgroup recruited additional members for each set of recommendations (Table 2.1). Alike selection of subgroup chairs, recruitment of group members was based on interest in specific aspects of sepsis and hands-on experience in ICUs in resource-limited settings. Additional group members were appointed by the group heads to address content needs for the development process. Several group members had experience in “Grading of Recommendations, Assessment, Development and Evaluation” (GRADE) process and the use of the GRADEpro Guideline Development Tool [10].

2.4 Meetings

Initial Internet subgroup chair meetings established the procedures for literature review and drafting of tables for evidence analysis. Subgroup chairs continued work remotely via the Internet. Several meetings occurred at major international meetings, teleconferences, and electronic-based discussions among subgroup chairs and members from other subgroups.

In the first meetings, up to 10 clearly defined questions regarding specific aspects of care for sepsis patients were formulated, using the GRADEpro Guideline Development Tool [10]. These were reviewed for content and clarity by all subgroup members. After the approval by the subgroup members, the subgroup chairs split up, each one to seek for evidence for recommendations regarding three or four of the specific questions posed, seeking help from the subgroup members in identifying relevant publications where necessary. During this process, questions could be combined or adjusted—in some cases extra questions were added. The subgroup chairs summarized the evidence and formulated the recommendations after interactive telephone conferences. These were communicated among subgroup members. After their approval, the subgroup chairs summarized the evidence in a report, which was then sent for approval to all members of all eight subgroups.

2.5 Search Process

The search for literature followed the same methods as described for the development of the Surviving Sepsis Campaign guidelines [11]. In case a question was identical to one in those guidelines, the subgroup chairs searched for additional articles, specifically (new) investigations or meta-analyses related to the questions, in a minimum of one general database (i.e., MEDLINE, EMBASE) and the Cochrane Libraries. Furthermore, subgroup members paid specific attention to identify publication originating in low- and middle-income countries.

2.6 Grading of Recommendations

The subgroup chairs followed the principles of the GRADE process as described for the development of the Surviving Sepsis Campaign guidelines [11]. In short, GRADE classifies the quality of evidence as high (grade A), moderate (grade B), low (grade C), or very low (grade D) and recommendations as strong (grade 1) or weak (grade 2). The factors influencing this classification are presented in Table 2.2.

Table 2.2 Quality of evidence
Full size table

Different from the grading of recommendations in the Surviving Sepsis Campaign guidelines [11], the subgroup chairs paid extensive attention to several other factors as used before, but now focusing on resource-limited settings, i.e., availability and feasibility in resource-limited ICUs, affordability for low-resource ICUs, and last but not the least its safety in resource-limited ICUs (Table 2.3).

Table 2.3 Strong versus weak recommendationsa
Full size table

A strong recommendation was worded as “we recommend” and a weak recommendation as “we suggest.” Some recommendations remained as ungraded best practice statements, when in the opinion of the subgroup members, such recommendations were clear, clinically relevant, likely to result in benefit, supported by indirect evidence, and unsuitable for a formal evidence generation and review process (opportunity cost) [12].

2.7 Reporting

Each report was edited for style and form, with final approval by subgroup heads and then by the entire “Sepsis in Resource-Limited Settings” guidelines group.