Background: Sepsis is a major reason for intensive care unit (ICU) admission, also in resource-poor settings. ICUs in low-and middle-income countries (LMICs) face many challenges that could affect patient outcome. Aim: To describe differences between resource-poor and resource-rich settings regarding the epidemiology, pathophysiology, economics and research aspects of sepsis. We restricted this manuscript to the ICU setting even knowing that many sepsis patients in LMICs are treated outside an ICU. Findings: Although many bacterial pathogens causing sepsis in LMICs are similar to those in high-income countries, resistance patterns to antimicrobial drugs can be very different; in addition, causes of sepsis in LMICs often include tropical diseases in which direct damaging effects of pathogens and their products can sometimes be more important than the response of the host. There are substantial and persisting differences in ICU capacities around the world; not surprisingly the lowest capacities are found in LMICs, but with important heterogeneity within individual LMICs. Although many aspects of sepsis management developed in rich countries are applicable in LMICs, implementation requires strong consideration of cost implications and the important differences in resources. Conclusions: Addressing both disease-specific and setting-specific factors is important to improve performance of ICUs in LMICs. Although critical care for severe sepsis is likely cost-effective in LMIC setting, more detailed evaluation at both at a macro-and micro-economy level is necessary. Sepsis management in resource-limited settings is a largely unexplored frontier with important opportunities for research, training, and other initiatives for improvement.

PurposeUlinastatin, a serine protease inhibitor, inhibits several pro-inflammatory proteases and decreases inflammatory cytokine levels and mortality in experimental sepsis. We studied the effect of ulinastatin on 28-day all-cause mortality in a double-blind trial in patients with severe sepsis in seven Indian hospitals.MethodsPatients with sepsis were randomized within 48 h of onset of one or more organ failures to receive intravenous administration of ulinastatin (200,000 IU) or placebo 12 hourly for 5 days.ResultsOf 122 randomized subjects, 114 completed the study (55 receiving ulinastatin, 59 receiving placebo). At baseline, the mean APACHE II score was 13.4 (SD = 4.4), 48 (42 %) patients were receiving mechanical ventilation, 58 (51 %) were on vasopressors, and 35 % had multiple organ failure. In the modified intention-to-treat analysis (patients receiving six or more doses of study drugs), 28-day all-cause mortality was 7.3 % with ulinastatin (4 deaths) versus 20.3 % (12 deaths) with placebo (p = 0.045). On multivariate analysis too, treatment with ulinastatin (odds ratio 0.26, 95 % CI 0.07–0.95; p = 0.042) independently decreased 28-day all-cause mortality. However, the mortality difference did not reach statistical significance in the intention-to-treat analysis [10.2 % (6/59 deaths) with ulinastatin versus 20.6 % (13/63 deaths) in the placebo group; p = 0.11]. The ulinastatin group had lower incidence of new-onset organ failure (10 vs. 26 patients, p = 0.003), more ventilator-free days (mean ± SD 19.4 ± 10.6 days vs. 10.2 ± 12.5 days, p = 0.019), and shorter hospital stay (11.8 ± 7.1 days vs. 24.2 ± 7.2 days, p < 0.001).ConclusionsIn this pilot study, intravenous administration of ulinastatin reduced mortality in patients with severe sepsis in the modified intention-to-treat analysis, but not in the intention-to-treat analysis.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-014-3278-8) contains supplementary material, which is available to authorized users.

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Purpose:The purpose was to develop an end-of-life care (EOLC) policy for patients who are dying with an advanced life limiting illness and to develop practical procedural guidelines for limiting inappropriate therapeutic medical interventions and improve the quality of care of the dying within an ethical framework and through a professional and family/patient consensus process.Evidence:The Indian Society of Critical Care Medicine (ISCCM) published its first guidelines on EOLC in 2005 [1] which was later revised in 2012.[2] Since these publications, there has been an exponential increase in empirical information and discussion on the subject. The literature reviewed observational studies, surveys, randomized controlled studies, as well as guidelines and recommendations, for education and quality improvement published across the world. The search terms were: EOLC; do not resuscitate directives; withdrawal and withholding; intensive care; terminal care; medical futility; ethical issues; palliative care; EOLC in India; cultural variations. Indian Association of Palliative Care (IAPC) also recently published its consensus position statement on EOLC policy for the dying.[3]Method:An expert committee of members of the ISCCM and IAPC was formed to make a joint EOLC policy for the dying patients. Proposals from the chair were discussed, debated, and recommendations were formulated through a consensus process. The members extensively reviewed national and international established ethical principles and current procedural practices. This joint EOLC policy has incorporated the sociocultural, ethical, and legal perspectives, while taking into account the needs and situation unique to India.