Shock Syndromes II

Impaired systolic function (massive PE): Embolism dissolution (thrombolytic therapy) or removal

(surgical or catheter thrombectomy)

Thrombolytic agents (Table 9) bind to the plasminogen/plasmin complex, which may be either

circulating or bound to the clot surface.

ii.

This binding hydrolyzes a peptide bond to form free plasmin. Circulating plasmin is quickly

neutralized by α-antiplasmin, but fibrin-bound plasmin subsequently hydrolyzes bonds within

the clot matrix, leading to clot lysis.

iii.

As such, thrombolytic agents can lead to rapid PE dissolution and a subsequent decrease in RV

afterload (pulmonary vascular resistance), but they may also cause bleeding.

Drug

Dose

Pearl

Initial

Infusion

Alteplasea

Total dose: 100 mg infused over 2 hr

Fibrin selective half-life: 5 min

Dose in cardiac arrest may be

50 mg

Reteplaseb

Two doses of 10 units IV push over 2 min,

given 30 min apart

Fibrin selective half-life: 13–16

min

Tenecteplaseb

< 60 kg: 30-mg push over

5–10 s

61–70 kg: 35-mg push

71–80 kg: 40-mg push

81–90 kg: 45-mg push

> 91 kg: 50-mg push

N/A

Fibrin selective (14-fold com-

pared with alteplase) half-life:

90–130 min; only need bolus

dose

Less expensive than alteplase

Streptokinaseb

250,000 units over 30 min

100,000 units/hr over 24 hr

Nonselective

Antigenic

Urokinasea

4400 units/kg over 10 min

4400 units/kg/hr over 12 hr

Nonselective

aIndicates FDA approved for the treatment of PE.

bIndicates drug is not FDA approved for the treatment of PE.

PE = pulmonary embolism.

2012;32:158-72.

iv.

In a 2004 meta-analysis, thrombolytic agents were not shown to decrease mortality when

evaluated among all patients with a PE compared with heparin alone (6.7% vs. 9.6%; OR 0.67

[95% CI, 0.40–1.12]), but they may improve outcomes in patients with an increased risk of

death. As such, early PE-related mortality risk stratification is necessary to guide thrombolytic

therapy administration.

guidelines not by clot burden, but by acute PE causing hemodynamic changes: Hypotension

(SBP less than 90 mm Hg for at least 15 minutes or requiring vasoactive support not

from another cause), pulselessness, or bradycardia (heart rate less than 40 beats/minute

with signs of shock). The 2019 European Society of Cardiology (ESC) and European

Respiratory Society (ERS) guidelines for acute PE define hemodynamic instability as

including one of the following presentations:

of 90 mm Hg or greater despite adequate filling status AND end-organ hypoperfusion),

or