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Initial Volume Resuscitation and EGDT for Severe Sepsis/Septic Shock
*PulmCCM is not affiliated with the Surviving Sepsis Campaign.
An approach including early goal directed therapy with aggressive initial fluid resuscitation has been considered a cornerstone of initial therapy for severe sepsis and septic shock, since a single-center randomized trial showed such a strategy initiated in the emergency department improved survival from septic shock.
Early Goal-Directed Therapy for Severe Sepsis/Septic Shock
For patients with tissue hypoperfusion from sepsis* the Surviving Sepsis Guidelines advise volume resuscitation should start immediately and follow an institutional protocol. The goals during the first 6 hours of resuscitation should be (Grade 1C):
- Mean arterial pressure (MAP) ≥ 65 mm Hg;
- Central venous pressure (CVP) 8-12 mm Hg (12-15 mm Hg in patients receiving mechanical ventilation or with known preexisting decreased ventricular compliance);
- Urine output ≥ 0.5 mL/kg/hr (35 mL/hr for someone weighing 70 kg or 154 lbs);
- Central venous oxygen saturation (from the superior vena cava) ≥ 70%, or mixed venous oxygen saturation (from a pulmonary artery catheter) ≥ 65%.
Crystalloid is recommended for initial fluid resuscitation for severe sepsis and septic shock (Grade 1B). Hydroxyethyl starch (hetastarch) should not be used as therapy for sepsis, according to U.S. and European regulatory authorities (Grade 1B).
A minimum of 30 ml/kg of crystalloids (1.5-3 liters) is advised for most patients to qualify as adequate fluid resuscitation (Grade 1C), but fluid should be aggressively infused for as long as the patient continues to improve hemodynamically (ungraded recommendation). A portion of resuscitation fluids may be given as "albumin-equivalent" (Grade 1C).
Vasopressors should be begun within 6 hours for patients with hypotension despite aggressive initial fluid resuscitation (i.e., septic shock), to maintain a mean arterial pressure ≥ 65 mm Hg (Grade 1C).
* Hypoperfusion is most often defined as hypotension after a challenge with IV fluid (2 liters crystalloid has been suggested for volume-replete patients), and/or blood lactate ≥ 4 mmol/L. Severe sepsis can also be defined by sepsis-induced organ dysfunction in the presence of a preserved blood pressure.
Blood Transfusions and Dobutamine for Severe Sepsis / Septic Shock
Transfusion of packed red blood cells to a hematocrit of 30% and/or dobutamine infusion (to maximum 20 μg/kg/min) are considered optional therapies in the Surviving Sepsis Guidelines, for patients with low central / mixed venous oxygen saturations despite volume resuscitation and vasopressor administration. (Strength: not graded)
Neither blood transfusion nor dobutamine have been well-studied in isolation as treatments for severe sepsis or septic shock. Dobutamine and blood transfusions are commonly included as elements of "care bundles" for early goal directed therapy for severe sepsis / septic shock, but their contribution (if any) to the observed improved outcomes with use of these bundles is unknown.
Packed red blood cell transfusions are considered particularly controversial as a routine element of care for patients with severe sepsis. Red blood cell transfusions may improve oxygen delivery to underperfused tissues, but blood transfusions are potentially harmful in critical illness, including in patients with severe sepsis and septic shock.
Targeting Lactate in Severe Sepsis May Help
The Surviving Sepsis Guidelines also suggest that for patients with severe sepsis with high lactate levels, physicians serially measure lactate levels and seek to normalize the lactate level as an additional goal/target of therapy for severe sepsis / septic shock. The rationale is that some patients with severe sepsis and elevated lactate are at increased risk for mortality, despite a normal ScVO2. Randomized trials have examined targeted reductions of lactate (lactate clearance) as a distinct or complementary goal in early therapy for severe sepsis/septic shock, with one showing a suggestion of additional benefit from targeting lactate reductions in addition to the usual sepsis treatment goals. (Grade 2C)
In patients whose blood pressure can be restored to normal after fluid resuscitation, but still have lactate elevations ≥ 4 mmol/L (without hypotension), goal-directed therapy with serial measurements of CVP, ScVO2 and lactate should continue until these parameters improve. (Strength: Not graded)
"Late" Goal-Directed Therapy for Severe Sepsis/Septic Shock?
Early goal-directed therapy with initial aggressive fluid resuscitation should begin as soon as possible after sepsis is recognized or suspected. Most patients with severe sepsis and septic shock present in the emergency department, and the original EGDT trial protocol initiated treatment in the ED. However, adherence with EGDT is low in emergency departments, even those with formal sepsis protocols in place. There are many potential barriers to rapid initiation of goal directed therapy for sepsis in the ED, including the need to place a central venous catheter. Here's a great podcast from Scott Weingart's EMCrit on why the diagnosis and aggressive treatment of severe sepsis and septic shock doesn't always start in the emergency department.
Guide to Recommendations’ Strengths and Supporting Evidence in the Surviving Sepsis Guidelines:
- 1 = strong recommendation;
- 2 = weak recommendation or suggestion;
- A = good evidence from randomized trials;
- B = moderate strength evidence from small randomized trial(s) or upgraded observational trials;
- C = low strength evidence, well-done observational trials with control randomized controlled trials
- D = very low strength evidence, downgraded controlled studies or expert opinion.
PulmCCM is not affiliated with the Surviving Sepsis Guidelines or the Surviving Sepsis Campaign.