Table 4.

Hemodynamic Support and Adjunctive Therapy

Fluid therapy

Strength of recommendation and quality of evidence have been assessed using the GRADE criteria, presented in brackets after each guideline. For added clarity: • Indicates a strong recommendation or “we recommend”; ○ indicates a weak recommendation or “we suggest”

• Fluid-resuscitate using crystalloids or colloids.(1B)

• Target a CVP of ≥ 8 mm Hg (≥ 12 mm Hg if mechanically ventilated).(1C)

• Use a fluid challenge technique while associated with a haemodynamic improvement.(1D)

• Give fluid challenges of 1000 ml of crystalloids or 300–500 ml of colloids over 30 min. More rapid and larger volumes may be required in sepsis-induced tissue hypoperfusion.(1D)

• Rate of fluid administration should be reduced if cardiac filling pressures increase without concurrent hemodynamic improvement.(1D)

Vasopressors

• Maintain MAP ≥ 65 mm Hg.(1C)

• Norepinephrine or dopamine centrally administered are the initial vasopressors of choice.(1C)

○ Epinephrine, phenylephrine or vasopressin should not be administered as the initial vasopressor in septic shock.(2C)

– Vasopressin 0.03 units/min maybe subsequently added to norepinephrine with anticipation of an effect equivalent to norepinephrine alone.

○ Use epinephrine as the first alternative agent in septic shock when blood pressure is poorly responsive to norepinephrine or dopamine.(2B)

• Do not use low-dose dopamine for renal protection.(1A)

• In patients requiring vasopressors, insert an arterial catheter as soon as practical.(1D)

Inotropic therapy

• Use dobutamine in patients with myocardial dysfunction as supported by elevated cardiac filling pressures and low cardiac output.(1C)

• Do not increase cardiac index to predetermined supranormal levels.(1B)

Steroids

○ Consider intravenous hydrocortisone for adult septic shock when hypotension remains poorly responsive to adequate fluid resuscitation and vasopressors.(2C)

○ ACTH stimulation test is not recommended to identify the subset of adults with septic shock who should receive hydrocortisone.(2B)

○ Hydrocortisone is preferred to dexamethasone.(2B)

○ Fludrocortisone (50 μg orally once a day) may be included if an alternative to hydrocortisone is being used which lacks significant mineralocorticoid activity. Fludrocortisone is optional if hydrocortisone is used.(2C)

○ Steroid therapy may be weaned once vasopressors are no longer required.(2D)

• Hydrocortisone dose should be < 300 mg/day.(1A)

• Do not use corticosteroids to treat sepsis in the absence of shock unless the patient's endocrine or corticosteroid history warrants it.(1D)

Recombinant human activated protein C (rhAPC)

○ Consider rhAPC in adult patients with sepsis-induced organ dysfunction with clinical assessment of high risk of death (typically APACHE II ≥ 25 or multiple organ failure) if there are no contraindications.(2B,2Cforpost-operativepatients)

• Adult patients with severe sepsis and low risk of death (eg: APACHE II<20 or one organ failure) should not receive rhAPC.(1A)