By James McFeely, MD

Medical Director, Critical Care Units, Alta Bates Summit Medical Center, Berkeley, CA

Dr. McFeely reports no financial relationships relevant to this field of study.

The Surviving Sepsis Campaign recently published an update to the 2012 guidelines for management of sepsis and septic shock.1,2 The document incorporates literature published through July 2016. Pediatric guidelines, included in previous documents, have been removed from this version. Although the length of the paper is somewhat intimidating (74 pages, with 93 statements or recommendations regarding sepsis management and 655 references), fortunately for the bedside clinician, recommendations have been enumerated in table form. In addition, there is an accompanying article with recommendations on how this guideline may be approached.3

The panel of experts was divided into five different study sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Professional librarians performed independent literature searches. There was no industry input into guideline development, and no industry representatives were present during any of the deliberations. The 2012 guidelines were reassessed for relevance, and new questions were submitted for inclusion based on research since the last revision.

The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to assess the quality of the information and to determine the strength of recommendations.4 Three levels of statements or recommendations were made: strong (“most patients would accept that intervention and most clinicians should use it in most situations”), weak (“desirable effects of adherence to a recommendation probably will outweigh undesirable effects but with less confidence in these trade-offs”), and best practice statements, which are strong recommendations with unequivocal benefit but where evidence is hard to summarize or access using GRADE methodology.5 Examples of best practice statements include: Treat sepsis as a medical emergency, minimize level of sedation in ventilated patients, and discuss goals of care and prognosis with patients and families.

The campaign goes so far as to state that strong recommendations could be used as quality criteria or performance metric indicators. Several strong recommendations list therapies that are not appropriate for the septic patient. Table 1 lists those interventions not recommended by the current guidelines.

Table 1: Strongly NOT Recommended by 2016 Guidelines

  • Routine combination antibiotic therapy for neutropenic sepsis/bacteremia
  • Hydroxyethyl starches for volume repletion
  • Renal dose dopamine
  • Erythropoietin for sepsis-associated anemia
  • Anti-thrombin III
  • High-frequency oscillatory ventilation for sepsis-induced ARDS
  • Beta-agonists without evidence of bronchospasm
  • Routine use of pulmonary artery catheters with sepsis-induced ARDS
  • Total parenteral nutrition in the first seven days
  • Omega-3 fatty acids as an immune supplement
  • Selenium
  • Glutamine

Any references to the three- and six-hour bundles of care have been removed; these are replaced with strong recommendations for rapid administration of fluids (within three hours) and antibiotics (within one hour) and flexible options for dynamic reassessment of adequacy of resuscitation.

One striking recommendation is the strong recommendation for using prone positioning in acute respiratory distress syndrome (ARDS) patients. Tables 2 and 3 list the strong recommendations sorted by section. The bedside clinician would be well-served to review all the tables included in the article, paying particular attention to the strong recommendations in each subsection.

Table 2: Strong POSITIVE Recommendations (Hemodynamics, Infection)

  • 30 mL/kg crystalloid within the first three hours
  • Initial target mean arterial pressure of 65 mmHg in septic shock requiring vasopressors
  • Norepinephrine as first-line vasopressor
  • Administer antibiotics as soon as possible, preferably within one hour of recognition
  • Empiric broad-spectrum therapy to cover all likely pathogens
  • Conservative fluid strategy in ARDS in patients without hypoperfusion

Table 3: Strong POSITIVE Recommendations (Adjunctive Therapies, Metabolic, and Ventilation)

  • Transfuse packed red blood cells when Hgb < 7 unless extenuating circumstances (bleeding, myocardial infarction, severe hypoxemia)
  • Target tidal volume 6 mL/kg for ARDS, plateau pressure upper limit 30 cm H2O
  • Prone positioning for ARDS where PaO2/FiO2 < 150
  • Raise head of bed 30-45 degrees in mechanically ventilated patients, spontaneous breathing trials, and a weaning protocol
  • Blood glucose control via protocol targeting blood glucose < 180
  • Pharmacologic venous thromboembolism prophylaxis where able, low molecular weight heparin preferred
  • Stress ulcer prophylaxis for patients with risk factors
  • Incorporate goals of care into treatment planning including palliative care principles where appropriate

The weak recommendations also are very important, but require more risk/benefit analysis before implementation in any given case. The best practice statements, by and large, appear to be non-controversial, common sense recommendations that most clinicians already should be following.

With this update, the Surviving Sepsis Campaign has done a remarkably good job summarizing the current state of the sepsis literature. It will serve as a reliable reference for bedside providers, administrators, and third-party payers as they develop their performance metrics.

In addition, its robust reference section is a valuable resource for researchers or others who wish to conduct a thorough investigation on any of the specifics recommended in the article.

All ICU clinicians need to review these guidelines, compare them with their current practices, and develop plans for implementation in the near future.

REFERENCES

  1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Crit Care Med 2017;45:486-552.
  2. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Intensive Care Med 2017;43:304-377.
  3. Dellinger RP, Schorr CA, Levy MM. A users’ guide to the 2016 Surviving Sepsis Guidelines. Intensive Care Med 2017;43:299-303.
  4. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-926.
  5. Guyatt GH, Schünemann HJ, Djulbegovic B, Akl EA. Guidelines panels should not GRADE good practice statements. J Clin Epidemiol 2015;68:597-600.