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Introduction
Evidence informing the management of patients with sepsis and septic shock mainly derives from research in resource-rich settings. Knowledge translation to intensive care units (ICUs) in resource-limited settings is limited by restricted availability of skilled staff, equipment, and laboratory support, compounded by infrastructure and logistical challenges. Consequently, we developed recommendations relating to core elements of general supportive care for patients with sepsis and septic shock in resource-limited settings. Our recommendations are built on guidelines from the Surviving Sepsis Campaign [1] and the Global Intensive Care Working Group of the European Society of Intensive Care Medicine [2], as well as on a search for additional recent evidence from resource-limited ICUs.
Clinicians with direct experience in resource-limited ICUs developed recommendations by adapting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tools [3]. Similar to our group’s previous publications (e.g., see [4]), quality of evidence was assessed as high to very low. Recommendations were stated as strong or weak on the basis additionally of indirectness of evidence, magnitude of effects, and availability, feasibility, and safety in resource-limited ICUs. We consulted the World Health Organization Essential Medicines List when considering availability of medications (available at http://www.who.int/medicines/publications/essentialmedicines/en/). When necessary, evidence from resource-rich ICUs was adopted after pragmatic experience-based appraisal (see online supplement). We also made several good practice statements [5].
Results and recommendations
The literature search for additional evidence from resource-limited ICUs identified several guidelines [6,7,8]; the only randomized trials were of metformin for the treatment of hyperglycemia [9,10,11]. Key recommendations are provided in Table 1. Considerations informing each recommendation are described below; more detailed information on the literature search and grading of recommendations is included in the online supplement.
Corticosteroids
Low-dose corticosteroids are readily available and inexpensive; current evidence supports their use in septic patients with refractory shock, pending completion of additional trials (NCT00625209, NCT01448109). Data from recent systematic reviews suggest no increased risk of gastrointestinal bleeding, superinfection, or neuromuscular weakness, but a possible increased risk of hyperglycemia and hypernatremia. We did not locate trials or relevant observational studies from low-resource ICUs.
Sedation for ventilated patients
Relevant considerations include availability of selected opiates and benzodiazepines (although available in principle, actual availability may vary); the requirement for nursing and medical expertise in the administration and monitoring of sedation to care for mechanically ventilated patients with sepsis; and the potential for delayed recognition of and physician response to a self-extubated patient requiring reintubation, particularly outside of weekday daytime hours. Existing literature largely derives from ICUs with high-intensity nurse staffing, reinforcing the need for caution with lighter sedation strategies in ICUs with fewer nurses.
Neuromuscular blockade for ventilated patients
Selected neuromuscular blocking agents are available in principle in resource-limited settings, although actual availability may vary. Unresolved issues include method of administration (bolus vs. continuous, which may increase complexity and costs) and monitoring via nerve stimulator vs. clinical judgment. Attentive nursing is required to care for patients receiving neuromuscular blockade. We did not locate trials or relevant observational studies from low-resource ICUs but expect additional data (NCT02509078) to inform this question.
Venous thromboembolism prophylaxis
Pharmacological prophylaxis is generally available in resource-limited ICUs and can be delivered feasibly and safely. Less available mechanical modalities may further decrease thromboembolism risk in combination with pharmacological prophylaxis and are potentially reusable. We identified one relevant guideline [8].
Stress ulcer prophylaxis
Proton pump inhibitors and histamine-2 receptor antagonists are generally available in resource-limited ICUs and can be delivered feasibly and safely. Increased risks of ventilator-associated pneumonia and Clostridium difficile infection are not definitively established. We did not locate trials or relevant observational studies from low-resource ICUs; risks and benefits will be informed by additional trials (NCT02467621; NCT02290327).
Glycemic control
We identified a recent Indian consensus guideline on blood glucose management [7] and three small Iranian trials of metformin [9,10,11]. Critical illness-associated hyperglycemia is common, and short-acting insulin is widely available and inexpensive. However, blood glucose control with continuous intravenous insulin is a complex intervention, with an increased risk for hypoglycemia when monitoring is insufficient. Frequent blood glucose measurements may only be feasible with capillary blood testing, a method that is less accurate than venous or arterial sampling. We make no recommendations regarding metformin in the absence of adequate randomized trial evidence and concern over the risk of lactic acidosis.
Enteral nutrition
Enteral feeding is feasible and readily available. Where commercial feeds are not available or expensive, hospital-prepared foods may be administered. Parenteral nutrition is not routinely available. One small trial of early vs. later nasogastric nutrition in ward patients with malaria and depressed consciousness found an increased aspiration risk, but no trials or observational studies from low-resource ICUs were identified. We note some controversy among published guidelines regarding the timing and amount of enteral feeding.
Renal replacement therapy
Current guidelines do not address the choice of renal replacement modality. Recent observational literature has emphasized the high potential for feasible and cost-effective widespread deployment of peritoneal dialysis (PD) to very low resource settings, notwithstanding challenges of patient selection, ongoing training, and program sustainability [12].
Restrictive fluid management in patients no longer in shock
Current guidelines make recommendations for initial fluid resuscitation, but not for fluid management in patients who are no longer in shock. We did not find trials of conservative fluid strategies from resource-limited ICUs. Challenges in designing such trials include managing trade-offs between complex protocols that consider individual patient physiology and practical limitations of monitoring technologies and frequency of clinical reassessments.
Conclusion
We present recommendations for core elements of general supportive care of patients with sepsis or septic shock in resource-limited ICUs, incorporating considerations of availability, feasibility, affordability, and safety. The paucity of evidence from resource-limited settings underscores the urgent need for rigorous trials, since treatment effects may differ from trials conducted in high-income settings [13]. Given the immense variability in healthcare worker and technical capacity within resource-limited ICUs, we recognize that clinicians may have to further adapt this set of recommendations on the basis of site-specific circumstances.
References
Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, Kumar A, Sevransky JE, Sprung CL, Nunnally ME, Rochwerg B, Rubenfeld GD, Angus DC, Annane D, Beale RJ, Bellinghan GJ, Bernard GR, Chiche JD, Coopersmith C, De Backer DP, French CJ, Fujishima S, Gerlach H, Hidalgo JL, Hollenberg SM, Jones AE, Karnad DR, Kleinpell RM, Koh Y, Lisboa TC, Machado FR, Marini JJ, Marshall JC, Mazuski JE, McIntyre LA, McLean AS, Mehta S, Moreno RP, Myburgh J, Navalesi P, Nishida O, Osborn TM, Perner A, Plunkett CM, Ranieri M, Schorr CA, Seckel MA, Seymour CW, Shieh L, Shukri KA, Simpson SQ, Singer M, Thompson BT, Townsend SR, Van der Poll T, Vincent JL, Wiersinga WJ, Zimmerman JL, Dellinger RP (2017) Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 43(3):304–377
Dunser MW, Festic E, Dondorp A, Kissoon N, Ganbat T, Kwizera A, Haniffa R, Baker T, Schultz MJ, Global Intensive Care Working Group of European Society of Intensive Care Medicine (2012) Recommendations for sepsis management in resource-limited settings. Intensive Care Med 38:557–574
Schünemann H, Brożek J, Guyatt G, Oxman A (eds) (2013) GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group. www.guidelinedevelopment.org/handbook. Accessed 6 Jan 2017
Serpa Neto A, Schultz MJ, Festic E (2016) Ventilatory support of patients with sepsis or septic shock in resource-limited settings. Intensive Care Med 42:100–103
Guyatt GH, Alonso-Coello P, Schunemann HJ, Djulbegovic B, Nothacker M, Lange S, Murad MH, Akl EA (2016) Guideline panels should seldom make good practice statements: guidance from the GRADE Working Group. J Clin Epidemiol 80:3–7
Hashmi M, Khan FH, bin Sarwar Zubairi A, Sultan ST, Haider S, Aftab S, Husain J, ul Haq A, Rao ZA, Khuwaja A, Sultan SF, Rais Z, Baloch R, Salahuddin N, Khan A, Sultan F, Chima K, Ali A, Ali G (2015) Developing local guidelines for management of sepsis in adults: sepsis guidelines for Pakistan (SGP). Anaesth Pain Intensive Care 19(2):196–208
Mukherjee JJ, Chatterjee PS, Saikia M, Muruganathan A, Das AK, Diabetes Consensus Group (2014) Consensus recommendations for the management of hyperglycaemia in critically ill patients in the Indian setting. J Assoc Physicians India 62:16–25
Jacobson BF, Louw S, Buller H, Mer M, de Jong PR, Rowji P, Schapkaitz E, Adler D, Beeton A, Hsu HC, Wessels P, Haas S, South African Society of Thrombosis and Haemostasis (2013) Venous thromboembolism: prophylactic and therapeutic practice guideline. S Afr Med J 103:261–267
Panahi Y, Mojtahedzadeh M, Zekeri N, Beiraghdar F, Khajavi MR, Ahmadi A (2011) Metformin treatment in hyperglycemic critically ill patients: another challenge on the control of adverse outcomes. Iran J Pharm Res 10:913–919
Mojtahedzadeh M, Jafarieh A, Najafi A, Khajavi MR, Khalili N (2012) Comparison of metformin and insulin in the control of hyperglycaemia in non-diabetic critically ill patients. Endokrynol Pol 63:206–211
Ansari G, Mojtahedzadeh M, Kajbaf F, Najafi A, Khajavi MR, Khalili H, Rouini MR, Ahmadi H, Abdollahi M (2008) How does blood glucose control with metformin influence intensive insulin protocols? Evidence for involvement of oxidative stress and inflammatory cytokines. Adv Ther 25:681–702
Smoyer WE, Finkelstein FO, McCulloch MI, Carter M, Brusselmans A, Feehally J (2016) “Saving Young Lives” with acute kidney injury: the challenge of acute dialysis in low-resource settings. Kidney Int 89:254–256
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 (2011) Mortality after fluid bolus in African children with severe infection. N Engl J Med 364:2483–2495
Murray MJ, DeBlock H, Erstad B, Gray A, Jacobi J, Jordan C, McGee W, McManus C, Meade M, Nix S, Patterson A, Sands MK, Pino R, Tescher A, Arbour R, Rochwerg B, Murray CF, Mehta S (2016) Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient. Crit Care Med 44:2079–2103
Critical Care Nutrition at the Clinical Evaluation Research Unit (CERU) (2015) Clinical practice guideline for nutrition support in the mechanically ventilated, critically ill adult patient. CERU, Kingston General Hospital/Queen’s University. http://www.criticalcarenutrition.com/. Accessed 6 Jan 2017
Acknowledgements
Group members of the Core Elements of General Supportive Care Subgroup: Mervyn Mer (Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa), Marcus J. Schultz (Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands & Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand), Neill K.J. Adhikari (Sunnybrook Health Sciences Centre & University of Toronto, Toronto, ON, Canada), Arthur Kwizera (Mulago National Referral Hospital, Kampala, Uganda), David Misango (Aga Khan University Hospital, Nairobi, Kenya), Sanjib Mohanti (Ispat General Hospital, Rourkela, Sundargarh, Odisha, India), Arjen Dondorp (Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand & Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands), Ary Serpa Neto (Hospital Israelita Albert Einstein, São Paulo, Brazil), and Jacobus Preller (Addenbrooke’s Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK).
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Members of the Sepsis in Resource-Limited Settings Group are listed in the online supplement.
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Mer, M., Schultz, M.J., Adhikari, N.K. et al. Core elements of general supportive care for patients with sepsis and septic shock in resource-limited settings. Intensive Care Med 43, 1690–1694 (2017). https://doi.org/10.1007/s00134-017-4831-z
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DOI: https://doi.org/10.1007/s00134-017-4831-z