Shock Syndromes I

iii.

During a shortage of norepinephrine in 2011, phenylephrine was used as an alternative for

patients with septic shock. Compared with normal use, in-hospital mortality was higher during

the norepinephrine shortage (absolute risk increase of 3.7%; 95% CI, 1.5%–6.0%; p=0.03).

Because phenylephrine was the most commonly used vasoactive agent during the shortage

period, phenylephrine should be used cautiously in patients with circulatory shock.

iv.

Because phenylephrine is a pure α1-adrenergic agent, it is attractive for patients who develop

a tachyarrhythmia while receiving norepinephrine. Although phenylephrine has been used in

clinical practice for many years for this indication, no clinical trial data support this practice.

Dopamine is best used in a select patient population, including those with a low risk of

tachyarrhythmias (which is difficult to predict) or those with bradycardia-induced hypotension.

Low-dose (“renal dose” 2 mcg/kg/minute) dopamine should not be used to improve renal blood

flow and urinary output (renal protection).

Preliminary data suggest that midodrine helps decrease vasopressor duration in patients in the

convalescent phase of septic shock.

MIDAS was a multicenter, randomized, double-blind, placebo-controlled trial of patients with

hypotension admitted to an ICU requiring a single-agent vasopressor who could not be liberated

from vasopressors for at least 24 hours. Patients were randomized to receive midodrine 20 mg

every 8 hours or placebo. There was no difference in time to vasopressor discontinuation in the

136 included patients (23.5 hours of midodrine vs. 22.5 hours of placebo). Of note, this study

was not specific for patients with septic shock.

ii.

Further, larger studies are needed before midodrine is used in routine practice.

iii.

When midodrine is used for this indication, care should be taken to ensure appropriate

discontinuation after resolution of shock. Reports have noted inappropriate continuation of

midodrine that may have been found in the outpatient setting.

Dobutamine may be indicated in patients with evidence or suggestion of myocardial dysfunction.

A low CO is common in early septic shock but is often corrected with fluid resuscitation alone.

ii.

Myocardial dysfunction may persist despite fluid resuscitation, with 39% of patients having

left ventricular hypokinesia on ICU admission and an additional 21% of patients developing

hypokinesia 24–48 hours after ICU admission in one series.

iii.

If myocardial dysfunction leads to significantly impaired Do2, an inotrope such as dobutamine

(up to 20 mcg/kg/minute) may be indicated to improve CO.

iv.

Dobutamine should not be used to achieve a predetermined supranormal cardiac index or

Scvo2.

As noted previously, levosimendan, compared with placebo, did not lead to a significant difference

in the mean SOFA score in patients with sepsis. In a meta-analysis performed by the SSC,

levosimendan and dobutamine did not differ with respect to mortality (RR 0.83; 95% CI, 0.66–

1.05). Given these data, dobutamine is recommended as the preferred inotrope in patients with

septic shock.

The 2021 SSC guidelines do not recommend angiotensin II as a first-line agent because of the low

quality of evidence and lack of clinical experience in sepsis; however, they note that it may play a

role as an adjunctive vasopressor therapy.