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.

Table 1 Recommendations for core elements of general support for septic patients in resource-limited ICUs
Full size table

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.