Shock Syndromes I

high-dose norepinephrine (greater than 0.6 mcg/kg/minute) randomized patients to AVP

0.033 units/minute versus AVP 0.067 units/minute. The study was designed to evaluate

hemodynamic changes, not mortality. Patients randomized to the higher dose had a greater

reduction in norepinephrine requirements than did those allocated to the lower dose

(p=0.006). High-dose AVP did not lead to a significantly lower cardiac index than low-

dose AVP (as might be expected with this pure vasoconstrictor), but this finding is difficult

to interpret because most patients were receiving concomitant inotropes, and the study was

likely underpowered to assess this outcome.

norepinephrine doses (greater than 0.6 mcg/kg/minute) with a high CO.

ix.

Despite the unclear benefits of AVP on mortality, it offers an alternative mechanism to

catecholamines for vasoconstriction, and low-dose AVP is commonly used in practice (often as

the second vasoactive medication).

norepinephrine and vasopressin.

A randomized trial of patients with septic shock compared epinephrine with norepinephrine

with or without dobutamine. The groups did not differ in 28-day mortality (40% vs. 34%,

p=0.31), but patients allocated to epinephrine had significantly higher lactate concentrations on

day 1 (p=0.003) and lower arterial pH values on each of the first 4 study days. Caution should

be used in concluding that mortality does not differ between epinephrine and norepinephrine

because the study was powered to detect a 20% absolute difference in mortality rates, and a

smaller difference between agents cannot be ruled out.

ii.

The benefit of adding epinephrine to norepinephrine (whether this approach has a

norepinephrine-sparing effect or whether it is best used in norepinephrine failure) is unclear.

iii.

Because norepinephrine may cause tachycardia or tachyarrhythmias (often the impetus to

limit doses), alternative vasopressors may be added. If catecholamine vasopressors with β1-

adrenergic properties (e.g., epinephrine) are added to augment MAP in patients receiving

norepinephrine, they are unlikely to prevent tachyarrhythmias and will likely increase the risk

of this adverse effect.

iv.

In addition, epinephrine may preclude the use of lactate clearance as an initial resuscitation

goal because it increases lactate concentrations through increased production by aerobic

glycolysis (by stimulating skeletal muscle β2-adrenergic receptors), an effect that likely wanes

with continued epinephrine administration.

It seems most prudent to use epinephrine in patients receiving norepinephrine with a low MAP

who require CO augmentation.

Phenylephrine is no longer recommended by the SSC guidelines for use in patients with septic

shock because of limited clinical trial data.

Because of its afterload augmentation effects without β1-adrenergic properties, phenylephrine

may theoretically decrease SV and CO. As such, it is not recommended as a first-line vasopressor

in patients with septic shock who have decreased CO because of inadequate preload.

ii.

A small study (n=32) that randomized patients with septic shock to phenylephrine or

norepinephrine as first-line therapy found no difference in hemodynamic measures (including

CO) between agents in the first 12 hours of therapy. This finding is likely because of the

inotropic effect of myocardial α1-adrenergic receptor augmentation by phenylephrine. These

data are in contrast to the theoretical concerns with phenylephrine and warrant further study.