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Vasopressors are provided for septic shock that does not respond to fluid
resuscitation. Norepinephrine (Levophed), epinephrine, vasopressin, phenylephrine (Neo-
Synephrine), and dopamine are the most commonly used vasopressors for septic shock.
To achieve adequate fluid resuscitation, the Surviving Sepsis Guidelines advise at least 30 ml/kg
of crystalloids (1.5-3 liters) be infused for most patients (Grade 1C) in septic shock. Some
patients will require more IV fluids; fluid should be aggressively infused for as long as the
patient continues to improve hemodynamically (ungraded recommendation). A portion of infused
resuscitation fluid can be given as albumin-equivalent (Grade 1C).
Vasopressors should be promptly begun in patients in persistent septic shock despite fluid
resuscitation; vasopressors can be begun and continued simultaneously with fluid resuscitation,
especially in patients with severe hypotension. The Surviving Sepsis Guidelines advise the
following:
Epinephrine is considered the next-line agent for septic shock after norepinephrine in the
Surviving Sepsis Guidelines. When norepinephrine is insufficient to maintain MAP 65
mm Hg, epinephrine should be added to or substituted for norepinephrine (Grade 2B).
Vasopressin is not recommended for use as a single vasopressor for septic shock
(ungraded recommendation).
Vasopressin doses higher than 0.03 0.04 units/min are recommended to be reserved
only for dire situations of septic shock refractory to standard doses of multiple
vasopressors (ungraded recommendation).
Dobutamine should be tried for patients in septic shock who have low cardiac output
with high filling pressures while on vasopressors, or who have persistent evidence of
hypoperfusion after attaining an adequate mean arterial pressure and intravascular
volume (with or without vasopressors) (Grade 1C).
The goal of attaining a mean arterial pressure (MAP) of 65 mm Hg for patients receiving
vasopressors for septic shock is based on very limited evidence. The single research study cited
in the Surviving Sepsis Guidelines to support the goal of MAP 65 mm Hg enrolled only 10
patients. Accordingly, the Surviving Sepsis Guidelines advise that the optimal MAP should be
individualized during treatment of septic shock perhaps higher than 65 mm Hg in a patient
with hypertension and known atherosclerosis; perhaps lower than 65 mm Hg in a young healthy
patient with a baseline normal blood pressure and that other markers of perfusion such as
serum lactate, skin appearance and temperature, urine output, and mental status should
supplement the use of mean arterial pressure in all patients.
Why Norepinephrine (Levophed) for Septic Shock Instead of Other Vasopressors?
Norepinephrine (Levophed) is favored as the first-line vasopressor for septic shock in the
Surviving Sepsis Guidelines (Grade 1B). Norepinephrine increases mean arterial pressure
primarily through vasoconstriction, with little effect on heart rate, stroke volume, and cardiac
output; dopamine increases MAP primarily through an increase in cardiac output (by increasing
both heart rate and stroke volume). These characteristics make dopamine more likely than
norepinephrine to cause potentially harmful tachyarrhythmias.
Norepinephrine and dopamine have been compared directly in at least 6 randomized trials, and
less directly in meta-analyses. The Surviving Sepsis Campaigns own (unpublished) pooled
analysis of these trials showed a relative risk for death of 0.91 (0.83-0.99) with the use of
norepinephrine compared to dopamine as vasopressor therapy for septic shock. A 2012 meta-
analysis including randomized and observational trials also concluded dopamine brings an
increased risk for death compared with Levophed as a first-line vasopressor for septic shock.
Epinephrine is suggested as the next-line vasopressor after norepinephrine for septic shock, to
be added or substituted if norepinephrine is inadequate (Grade 2B). Epinephrine has been
compared to norepinephrine in at least 4 randomized trials, with no increase in the risk for death.
Epinephrine may increase lactate concentrations by stimulating skeletal muscles aerobic
metabolism, thereby interfering with the use of lactate as a marker of perfusion during treatment
of septic shock.
Phenylephrine can decrease stroke volume and is recommended to not be used except as
salvage therapy, in known high cardiac output states, or if norepinephrine has caused
tachyarrhythmias (Grade 1C).
Vasopressin (or its analogue terlipressin) has been compared to norepinephrine as a vasopressor
for septic shock in 9 randomized trials (n=963); vasopressin / terlipressin carried a (non-
significant) increased risk of death (albeit a lower risk of tachyarrhythmias) compared to
norepinephrine.
1 = strong recommendation;