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Is the Tail Wagging the Dog in Sepsis?

Haniffa, Rashan, FRCA; Beane, Abi, MSc; Dondorp, Arjen M., PhD

doi: 10.1097/CCM.0000000000003160
Online Letters to the Editor

Network for Improving Critical Care Systems and Training, Colombo, Sri Lanka, and University College London, London, United Kingdom;

University of Amsterdam, Amsterdam, The Netherlands, and Network for Improving Critical Care Systems and Training, Colombo, Sri Lanka;

Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand, and University of Oxford, Oxford, United Kingdom

Dr. Dondorp received support for article research from Wellcome Trust/Charity Open Access Fund. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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To the Editor:

Machado and Azevedo (1), in their article published in a recent issue of Critical Care Medicine, highlight both the extensive global inequalities due to sepsis and the very limited data from low- and middle-income countries (LMICs). The authors correctly point out that the burden of sepsis—as defined currently and notwithstanding the scarcity of reliable data—is higher in LMICs, not least because nearly 85% of the global population lives outside high-income countries (HICs). While acknowledging that the consequences of infection to individuals and families are frequently catastrophic and often higher in LMIC when compared with HIC, this disparity is neither novel nor exclusive to sepsis (2).

Disease or syndrome definitions, especially when globally applicable, can help in public awareness, timely detection, protocolized management, and standardized evaluation (including in the testing of interventions and quality improvement measures). Such definitions can also assist in the transfer of knowledge between diverse settings and enable the evaluation of the effectiveness of any proposed interventions. However, the current conceptual sepsis definition aspires to include the consequences of diseases resulting from organisms as diverse as Escherichia, Mycobacterium, Staphylococcus, Burkholderia, Dengue virus, Leptospira, Trypanosoma, Plasmodium, Candida, and HIV (3). The feasibility of the diagnostic criteria and the effectiveness of interventions recommended by the Surviving Sepsis Campaign (SSC) have been questioned, especially for infections common in LMIC settings (4). Meanwhile, whether clinicians and researchers (and the wider public) in LMIC settings consider diseases resulting from specific infectious agents, for example, malaria, dengue, and melioidosis as sepsis either by diagnostic criteria or by instituting SSC treatment measures is not well known. Consequently, it is also not possible to ascertain to what extent the nonlabeling (or recognition) of these diseases as sepsis, the nonimplementation of SSC treatment measures, or the inability to rescue from the complications of such treatment (e.g., by instituting mechanical ventilation) are contributing to the reported high mortality and morbidity, work which is currently being undertaken by our group in LMIC.

Perhaps research should also ascertain whether there are systematic and relatively easily remediable themes for the poor outcomes in resource-limited settings due to acute illness, not only due to infection: the delayed recognition and rescue of the deteriorating patient due to unavailability of vital signs, the lack of repeated clinical examination, nontitration of inexpensive treatment interventions, and other barriers to clinical decision-making (5).

As the burden of infectious diseases in LMIC is greater than in HIC, should not the definition, diagnostic criteria and any treatment recommendations for sepsis, be fundamentally applicable to the major infectious causes of morbidity and mortality in such settings? The infeasibility of the diagnostic criteria is perhaps undermining its very purpose: clinician (and public) awareness, timely recognition, and protocolized management. Could the long overdue clamour for diagnostic criteria applicable to sepsis (for the many, not the few!), be an opportunity to better address therein the diversity of the infectious agents and the consequences of their infection?

Rashan Haniffa, FRCA

, Network for Improving Critical Care Systems and Training, Colombo, Sri Lanka, and University College London, London, United Kingdom;

Abi Beane, MSc

, University of Amsterdam, Amsterdam, The Netherlands, and Network for Improving Critical Care Systems and Training, Colombo, Sri Lanka;

Arjen M. Dondorp, PhD

, Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand, and University of Oxford, Oxford, United Kingdom

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REFERENCES

1. Machado FR, Azevedo LCPSepsis: A Threat That Needs a Global Solution. Crit Care Med 2018; 46:454–459
2. Samanamalee S, Sigera PC, De Silva AP, et alTraumatic brain injury (TBI) outcomes in an LMIC tertiary care centre and performance of trauma scores. BMC Anesthesiol 2018; 18:4. doi: 10.1186/s12871-017-0463-7
3. Singer M, Deutschman CS, Seymour CW, et alThe third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016; 315:801–810
4. Andrews B, Muchemwa L, Kelly P, et alSimplified severe sepsis protocol: A randomized controlled trial of modified early goal-directed therapy in Zambia. Crit Care Med 2014; 42:2315–2324
5. Beane A, De Silva AP, De Silva N, et alEvaluation of the feasibility and performance of existing Early Warning Score (EWS) to identify patients at risk of adverse outcomes in a low-middle income country (LMIC) setting: A longitudinal observational cohort study. BMJ Open 2018:e019387. doi: 10.1136/bmjopen-2017-019387
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