New Surviving Sepsis Guidelines Released

The 2016 Surviving Sepsis guidelines produced by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine have been released. Many of the guideline recommendations remain unchanged from previous versions but include indepth rationales from studies published since the 2012 guidelines were released. The 2016 guidelines cover the treatment of sepsis and septic shock in depth and include recommendations including fluid rescitation, vasopressor selection, antimicrobial therapy, mechanical ventilation, blood and blood products, insulin adminstration, DVT and stress ulcer prophylaxis, and nutrition therapy. A small summary of many of the guideline's recommendations pertinent to pharmacy are summarized below.

Fluid Resuscitation

• Initial fluid resucitation should involve 30 ml/kg of a crystalloid fluid (i.e. normal saline, lactated ringers) within the first 3 hours of sepsis presentation. This recommendation includes a statement that clinicians should understand that many patients will require more fluid than that to acheive hemodynamic goals. The use of central venous pressure (CVP) alone to guide fluid resucitation is not recomended. When CVP is within a normal range (8-12 mmhg), it does not respond as noticably to a fluid challenge as is seen when the CVP is low. However the use of CVP can be integrated into the clinicians patient assessment and used along with other physiologic variables (vital signs, urine output, ect) to direct fluid administration. In patients with an elevated lactate (due to tissue hypoperfusion), fluid rescucitation should continue until the lactate is normal. In studies that evaluated fluid resucitation with and without the guidance of lactate, there was a significant decrease in mortality among patients where lactate had been used to direct fluid adminstration.

Goal Mean Arterial Pressure and Vasopressor Selection

• The target mean arterial pressure (MAP) for patients in septic shock requiring vasopressor therapy is 65 mmHg. This is not a new recommendation and reflects recommendations from previous guidelines. However, since the last guidelines were released in 2012, several studies have evaluated targeting a goal MAP of 65 mmHg vs.a MAP of 85 mmHg. These studies have not shown a difference in major outcomes including mortality. However, there is an increased risk of vasopressor side effects when using higher doses to achieve these higher MAPs.
• Norepinephrine continues to be the first line vasopressor that is recommended.
• Vasopressin and epinephrine are appropriate add-on therapies if patients do not respond to norepinephrine. Vasopressin may also be used to decrease norepinephrine doses and subsequently reduce the risk of untoward effects such as gut or limb ischemia.

Screening programs and Quality Improvement

• Hospitals and health systems should have a screening system for sepsis. In the United States, this has essentially required to meet the Joint Commissions sepsis goals required to maintain accreditation. The guidelines recommend that performance improvement programs associated with this recommendation include a multi-professional group, including pharmacists. These performance improvemenat programs have been shown not only to increase compliance with guideline recomendations, but to decrease morality.

Infection Management: Cultures and Antimicrobial Treatment

• Appropriate cultures should always be obtained prior to gving antibiotics unless it would present a substantial delay in antimicrobial therapy. "Appropriate" cultures should include cultures directed at the suspected source(s) of infection and 2 sets of blood cultures. The guidelines suggest a timeframe of 45 minutes as an acceptable period in which to wait to be able to obtain cultures. If cultures can not be obtained within this 45 minute period, then clincians should go ahead and adminster antimicrobials. The resolution of sepsis and septic shock relies in large part on receiving appropriate antibiotics. Parenteral antibiotics should be given as soon as possible after cultures have been obtained, and no longer than one hour after sepsis presentation. Empiric therapy should include antimicrobials directed at all likely pathogens (including bacteria, viruses, and fungi) and should be deescalated once susceptibilities are available or the patient has shown notable clinical improvement.
• For patients in septic shock, empiric therapy that includes at least 2 antimicrobials from different classes that will provide coverage against all likely organisms should be included.
• The concept of patient-specific pharmacokinetics and pharmacodynamics and drug-specific properties should be considered when dosing antibioitics.
• Vancomycin, when used, should be dosed to acheive a trough of 15-20 mg/L. A loading dose of 25-30 mg/kg is recommended.
• When beta-lactams such as pipercillin/tazobactam are given by extended infusions, the first dose should be given as a "bolus" over 30 minutes and the extended infusion should begin with the second dose. This "loading dose" strategy was recommended to achieve facter therapeutic levels of these agents.
• Aminoglycosides should be dosed using once-daily dosing unless the patient has severe renal impairment.
• Fluoroquinolones should be prescribed at their maximal non-toxic dose.
• The use of the laboratory value procalcitonin should be used to help guide the decision to discontinue antimicrobial therapy.
• An average duration of therapy of 7-10 days is recommended. Clinical judgement and patient evaluation should guide the decision to shorten or extend antimicrobial administration.

Steroids

• IV hydrocortisone (200 mg/day) is only recommended when fluid rescucitation and vasopressor therapy fails to achieve hemodynamic stability. It is recommended to taper steroids once vasopressors are discontinued.

Glucose Control

Insulin infusion protocols, once adopted with a goal blood glucose of less than 110 mg/dL but later discouraged due to hypoglycemia, are once again recommended. However, under the new recommendation, a goal blood glucose of 180 mg/dL is recommened.

These and more recommendations can be viewed in the most recent version of the journal Intensive Care Medicine.

References

1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Int Care Med. 2017;doi:10.1007/s00134-017-4683-6