Abstract

BackgroundSepsis guidelines are widely used in high-income countries and intravenous fluids are an important supportive treatment modality. However, fluids have been harmful in intervention trials in low-income countries, most notably in sub-Saharan Africa. We assessed the relevance, quality and applicability of available guidelines for the fluid management of adult patients with sepsis in this region.MethodsWe identified sepsis guidelines by systematic review with broad search terms, duplicate screening and data extraction. We included peer-reviewed publications with explicit relevance to sepsis and fluid therapy. We excluded those designed exclusively for specific aetiologies of sepsis, for limited geographic locations, or for non-adult populations. We used the AGREE II tool to assess the quality of guideline development, performed a narrative synthesis and used theoretical case scenarios to assess practical applicability to everyday clinical practice in resource-constrained settings.ResultsPublished sepsis guidelines are heterogeneous in sepsis definition and in quality: 8/10 guidelines had significant deficits in applicability, particularly with reference to resource considerations in low-income settings. Indications for intravenous fluid were hypotension (8/10), clinical markers of hypoperfusion (6/10) and lactataemia (3/10). Crystalloids were overwhelmingly recommended (9/10). Suggested volumes varied; 5/10 explicitly recommended “fluid challenges” with reassessment, totalling between 1 L and 4 L during initial resuscitation. Fluid balance, including later de-escalation of therapy, was not specifically described in any. Norepinephrine was the preferred initial vasopressor (5/10), specifically targeted to MAP > 65 mmHg (3/10), with higher values suggested in pre-existing hypertension (1/10). Recommendations for guidelines were almost universally derived from evidence in high-income countries. None of the guidelines suggested any refinement for patients with malnutrition.ConclusionsWidely used international guidelines contain disparate recommendations on intravenous fluid use, lack specificity and are largely unattainable in low-income countries given available resources. A relative lack of high-quality evidence from sub-Saharan Africa increases reliance on recommendations which may not be relevant or implementable.

Highlights

  • Sepsis guidelines are widely used in high-income countries and intravenous fluids are an important supportive treatment modality

  • These were screened for full manuscript review (n = 499), of which 486 were excluded (Fig. 1)

  • Two out of ten guidelines exceeded a score of 70% indicating highly rigorous and robust guideline development processes (NICE and Surviving Sepsis Campaign recommendations) which reflects the resources available to develop them [9, 16]

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Summary

Introduction

Sepsis guidelines are widely used in high-income countries and intravenous fluids are an important supportive treatment modality. In sub-Saharan Africa (SSA), where endemic tropical infections and advanced HIV are prevalent, models suggest the incidence of sepsis is higher (1527/100,000 cases per year compared with 678/100,000 globally) and represents 30–65% of overall mortality in the region, but primary sepsisspecific data are limited [3]. Strategies for improving sepsis survival in low-income countries (LIC) have been limited by lack of robust evidence, insufficient resources in emergency care and conflicting data from high- and low-income settings. High-income countries have widely adopted guidelines developed by the Surviving Sepsis Campaign (SSC). Adherence to these guidelines in observational studies is associated with improved survival [5,6,7]. Randomised controlled trials from Africa in adults and children have demonstrated the potential for harm using bolus fluids in LIC [10,11,12]

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