Shock Syndromes I

ii.

Participants treated had more arrhythmias with dopamine than with norepinephrine. The

authors concluded that major changes to clinical practice are not needed but that selection of

vasopressors could be better individualized and could be based on clinical variables reflecting

hypoperfusion. This systematic review is limited by the small number of patients enrolled in

randomized studies of some agents (e.g., phenylephrine) and few studies with combination

therapy.

In a phase III study of patients with shock (the Angiotensin II for the Treatment of High-Output

Shock [ATHOS-3] study) (n=321) without evidence of a low CO (about 90% with sepsis), use

of angiotensin II, compared with placebo, more often led to a MAP response (MAP of 75 mm

Hg or greater or MAP increase of 10 mm Hg or greater, without an increase in open-label

vasopressor dose) at hour 3 (69.9% vs. 23.4%, p<0.001). Angiotensin II significantly reduced

the cardiovascular Sequential Organ Failure Assessment (SOFA) subscore at hour 48, but not

the total SOFA score. Patients in the angiotensin II group more often developed a thrombotic

event (12.9% vs. 5.1%, p=0.02), a new infection (30.1% vs. 19.0%, p=0.029), and delirium

(5.5% vs. 0.6%, p=0.036).

ii.

A post hoc analysis of patients from the ATHOS-3 study with acute kidney injury requiring

renal replacement therapy found that patients treated with angiotensin II had longer survival

(adjusted hazard ratio [HR] 0.44; 95% CI, 0.24–0.80) and were more likely to discontinue

renal replacement therapy within 7 days (adjusted HR 2.90; 95% CI, 1.29–6.52) than those

who received placebo.

iii.

One retrospective study evaluating angiotensin II use found that of the 270 included patients,

67% had a positive hemodynamic response 3 hours after its initiation. Of note, 92% of patients

were also receiving vasopressin at the time of angiotensin II initiation.

iv.

These evaluations suggest that angiotensin II is an effective vasopressor for patients with

vasodilatory shock, particularly in those with acute kidney injury, but outcomes-based studies

are needed before this agent is implemented into routine clinical practice.

Because of the increased risk of thrombosis associated with angiotensin II, concurrent venous

thromboembolism prophylaxis is recommended.

Levosimendan

In a study of patients with sepsis, adding blinded levosimendan for 24 hours compared with

placebo did not lead to a significant difference in the mean SOFA score (6.68 ± 3.89 vs. 6.06 ±

3.89, respectively, p=0.053). Mortality at 28 days also did not differ between the levosimendan

and placebo groups (34.5% vs. 30.9%, p=0.43). Patients in the levosimendan group more often

developed a supraventricular tachyarrhythmia (3.1% vs. 0.4%, p=0.04).

ii.

A study of levosimendan compared with placebo for 48 hours in patients with circulatory

shock after cardiac surgery was terminated early for futility. Thirty-day mortality did not

differ between the levosimendan and placebo groups (12.9% vs. 12.8%, p=0.97), nor did the

groups differ in duration of mechanical ventilation or incidence of cardiac arrhythmias.

iii.

These data suggest that levosimendan does not improve outcomes in patients with sepsis or

circulatory shock after cardiac surgery and should not be used in these patients.