Sepsis Guidelines Revisited
SPECIAL FEATURE
By James E. 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 a revised International Guidelines for the Management of Severe Sepsis and Septic Shock, updating its 2008 guidelines.1 A consensus committee of 68 experts, representing 30 international organizations, participated. Committee proceedings were conducted independently with no industry funding and were regulated by a formal conflict of interest policy. The 58-page document makes recommendations in three large categories: treatment of severe sepsis, general care of critically ill patients, and pediatric considerations. The authors follow the principles of Grading of Recommendations of Assessment Development Evaluation (GRADE)2 to determine quality of evidence from high (A) to very low (D) and strength of recommendation as strong (1) or weak (2).
In accordance with the GRADE system, the guidelines place greater emphasis on strength of recommendation than quality of evidence. Strong recommendations are described as "we recommend" and weak recommendations as "we suggest." The authors include literature available through the fall of 2012. Specific recommendations mentioned in this special feature are followed by their GRADE recommendation in parenthesis. The definitions of suspected sepsis, severe sepsis, and septic shock are based on consensus conference recommendations.3
INITIAL RESUSCITATION
Initial resuscitation of severe sepsis continues to follow the early goal-directed therapy (EGDT) guidelines, including a central venous pressure (CVP) of 8-12 mmHg, mean arterial pressure (MAP) of ≥ 65 mmHg, urinary output > 0.5 mL/kg/hr, and either superior vena cava oxygenation saturation (ScvO2) or mixed venous oxygen saturation (SvO2) of 70% or 65%, respectively (see Table 1).4 When sepsis is suspected, a new 3-hour bundle is recommended, including checking serum lactate level, obtaining blood cultures, administrating antibiotics, and giving 30 mL/kg crystalloid (increased from 20 mL/kg in the 2008 guidelines) for hypotension or lactate > 4 mmol/L. The 6-hour EGDT window includes administering vasopressors for hypotension not responding to fluids and measuring CVP and SvO2 in the event of persistent arterial hypotension despite volume resuscitation or a lactate > 4 mmol/L. Lactic acid levels should be followed.
| Table 1. Surviving Sepsis Campaign Bundles |
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Timing
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Measures to be completed
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In first 3 hours
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Crystalloid infusion, 30 mL/kg
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Measurement of serum lactate
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Appropriate cultures obtained, followed by administration of antibiotics
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In first 6 hours
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Vasopressors to keep mean arterial pressure > 65 mmHg
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If lactate > 4 mmol/L, or pressors needed:
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• Measurement of central venous pressure
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• Measurement of central venous oxygen saturation (SvO2)
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Monitoring of serum lactate if initial value abnormal
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Adapted from Dellinger RP, et al1 and Rivers E, et al.4
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HEMODYNAMIC SUPPORT
Crystalloids are the recommended fluid for the initial resuscitation of severe sepsis and septic shock (1B). Hydroxyethyl starches are not recommended (1B).5 Albumin is suggested for fluid resuscitation when patients require substantial amounts of crystalloid (2C).
Vasopressors (see Table 2) should be initiated to maintain a mean arterial pressure of 65 (1C). Norepinephrine is the first choice of vasopressor (1B).6 Epinephrine, added to and potentially substituted for norepinephrine, is the second agent recommended for use as needed to maintain an adequate MAP (2B). Vasopressin may be added to epinephrine either to raise MAP or to decrease norepinephrine dosage. Dopamine is not recommended except in highly selected patients who may have a low risk of tachyarrhythmia and/or have significant bradycardia. Phenylephrine is also not recommended except where norepinephrine has caused arrhythmias, when cardiac output is high, or as salvage therapy when combined with low-dose vasopressin (1C).
| Table 2. Vasopressors |
- Target mean arterial pressure (MAP)
at least 65 mmHg (1C)
- Norepinephrine (NE) first choice as agent (1B)
- Epinephrine second choice pressor (2B)
- Vasopressin (0.03 u/min) may be added to NE to decrease NE dose or raise MAP (ungraded)
- Phenylephrine not recommended except as salvage, when NE causes arrhythmias, or known high cardiac output state (1C)
- Dobutamine trial if myocardial dysfunction suggested, or ongoing hypotension after volume resuscitation (1C)
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Dobutamine may be administered or added to vasopressors in the presence of myocardial dysfunction as suggested by high cardiac filling pressures and low cardiac output or ongoing signs of hypoperfusion, despite adequate intravascular volume and mean arterial pressure (1C).
STEROIDS
Corticosteroids are not recommended to treat adult septic shock if fluids and vasopressor therapy alone are able to restore hemodynamic stability. If this is not achievable, then intravenous hydrocortisone at a dose of 200 mg per day is suggested (2C). Adrenocorticotropin stimulation tests are discouraged. Steroids should be tapered when pressors are no longer required and should not be administered for the treatment of sepsis in the absence of shock (1D). It is further suggested that hydrocortisone be given as a continuous infusion (2D).
SUPPORTIVE THERAPIES
Supportive therapies for severe sepsis are also discussed. As before, transfusion of packed red blood cells is recommended as part of EGDT. Once tissue hypoperfusion has resolved, the transfusion trigger decreases to a hemoglobin level of < 7 gm/dL (1B). Erythropoietin is not recommended as treatment for anemia associated with sepsis (1B). The guidelines suggest that fresh frozen plasma not be used to correct clotting abnormalities in the absence of bleeding or invasive procedures (2D). Antithrombin is not recommended (1B); and neither intravenous immunoglobulin (2B) nor intravenous selenium (2C) is suggested. The use of recombinant activated protein C (drotrecogin alpha; Xigris®) has been removed from the guidelines.
Tight gylcemic control has also been removed, in favor of a targeted upper blood glucose < 180 mg/dL(1A).7 Renal replacement therapy and management of ventilator bundles, nutrition, and goals of care are also discussed, with recommendations consistent with guidelines published elsewhere for those specific components of overall critical care.8,9 A large section of the guidelines focuses on the treatment of pediatric sepsis. These guidelines follow recommendations from the American College of Critical Care Medicine (see Table 3).10,11
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Table 3. Pediatric Resuscitation
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Similar definitions of sepsis and organ dysfunction to adult recommendations
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0 min
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Recognize altered level of consciousness and/or hypoperfusion
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5 min
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Start intravenous or intraosseous crystalloid bolus up to 60 mL/kg unless dyspnea or liver distention present
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15 min
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Fluid refractory shock: begin pressors (intravenous or intraosseous)
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• Dopamine for "cold shock"
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• Norepinephrine for "warm shock"
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60 min
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Admission to pediatric ICU
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If refractory shock:
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• Hydrocortisone
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• Monitor CVP and SVO2 (same goals as for adults)
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Persistent shock
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• Rule out pneumothorax, pericardial disease, and/or abdominal compartment syndrome
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• Consider extracorporeal membrane oxygenation
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Per new guidelines,1 based on recommendations of the American College of Critical Care Medicine (1C)10,11
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CONCLUSION
This publication is a timely and unbiased update in an important clinical area. The authors point out that the guidelines are not standards of care: Specific recommendations for individual patients must be individualized based on clinical criteria. The guidelines do an excellent job of collating all relevant recommendations and synthesizing the literature related to each point of discussion. Every hospital should adopt this document as its starting point for reassessing local management of sepsis.
REFERENCES
- Dellinger RP, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock, 2012. Crit Care Med 2013;41:580-637.
- Guyatt GH, et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008; 336:924-926.
- Levy MM, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003; 31:1250-1256.
- Rivers E, et al; Early Goal-Directed Therapy Collaborative Group. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-1377.
- Zarychanski R, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: A systematic review and meta-analysis. JAMA 2013;309:678-688. Erratum in JAMA 2013;309:1229.
- De Backer D, et al. Dopamine versus norepinephrine in the treatment of septic shock: A meta-analysis. Crit Care Med 2012;40:725-730.
- NICE-SUGAR Study Investigators. Intensive versus conventional glucose control in critically ill patients. N Engl J Med 2009;360:1283-1297.
- Vinsonneau C, et al. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: A multicentre randomised trial. Lancet 2006;368:379-385.
- Eichacker PQ, et al. Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes. Am J Respir Crit Care Med 2002;166:1510-1514.
- Brierley J, et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 2009;37:666-688. Erratum in Crit Care Med 2009;37:1536.
- Skinner SC, et al. Improved survival in venovenous vs venoarterial extracorporeal membrane oxygenation for pediatric noncardiac sepsis patients: A study of the Extracorporeal Life Support Organization registry. J Pediatr Surg 2012;47:63-67.
