In this episode I’ll:
1. Discuss an article comparing half-dose versus full-dose alteplase for the treatment of pulmonary embolism.
2. Answer the drug information question “Can enoxaparin be used as anticoagulation for PE following the administration of alteplase?”
3. Share a tip for responding to inpatient medical emergencies.
Half-Dose Versus Full-Dose Alteplase for Treatment of Pulmonary Embolism
Lead author: Tyree Kiser
Published in Critical Care Medicine July 2018
Direct comparative studies of 50 mg vs 100 mg alteplase for pulmonary embolism are lacking. Some clinicians prefer to use the lower dose of alteplase for pulmonary embolism with the hope that it may provide similar efficacy with reduced bleeding risk compared with 100mg. The authors sought to evaluate the effectiveness and safety of 50 mg versus 100 mg alteplase for treatment of pulmonary embolism.
The study was a retrospective cohort comparing outcomes in patients receiving half-dose (50 mg) versus full-dose (100 mg) alteplase for pulmonary embolism. The cohort of adult critically ill patients with acute pulmonary embolism was selected from data from 420 hospitals obtained from the Premier Healthcare Database.
This study included about 700 patients in the half-dose group and about 3000 patients in the full-dose group. At baseline, patients receiving half-dose alteplase required vasopressor therapy and invasive ventilation about half as frequently, compared with those receiveing full-dose alteplase. After propensity matching, half-dose alteplase was associated with increased treatment escalation, driven mostly by secondary thrombolysis (25.9% vs 7.3%; p < 0.01) and catheter thrombus fragmentation (14.2% vs 3.8%; p < 0.01). There was no statistical difference in in-hospital mortality, cerebral hemorrhage, gastrointestinal bleeding, acute blood loss anemia, use of blood products, or documented fibrinolytic adverse events.
The authors concluded:
Compared with full-dose alteplase, half-dose was associated with similar mortality and rates of major bleeding. Treatment escalation occurred more often in half-dose–treated patients. These results question whether half-dose alteplase provides similar efficacy with improved safety, and highlights the need for further study before use of half-dose alteplase therapy can be routinely recommended in patients with pulmonary embolism.
Because of the equivelant safety and higher rate of treatment escalation, I would not choose half-dose alteplase for PE. One extra benefit of this trial is that it quantified the rate of intracranial hemorrhage after alteplase for pulmonary embolism. This rate was less than 0.5% overall for the study group. This is very low compared to the roughly 6% expected rate of intracranial hemorrhage after alteplase is given for acute ischemic stroke. This implies that the intensity of neurologic monitoring after alteplase for PE may not need to be as intense as it is for ischemic stroke.
Drug information question
Q: Can enoxaparin be used as anticoagulation for PE following the administration of alteplase?
A: I prefer to use a heparin infusion in the immediate period after alteplase was administered.
My concern would be that the ability to shut off anticoagulation in the event of a bleed is easier with heparin than with enoxaparin. Heparin has a half-life of 1 to 2 hours. The half-life of enoxaparin is 2 to 4 times that of heparin, and the subcutaneous depot cannot be removed once administered. In addition, heparin can be completely reversed by protamine, whereas enoxaparin can only be partially reversed. Although the risk of bleeding from alteplase is much lower when given for PE compared with ischemic stroke, I prefer to be risk-averse and use heparin over enoxaparin immediately after alteplase.
Tip for responding to inpatient medical emergencies
When a patient needs vasopressor therapy, don’t worry about peripheral vs central venous access until after the vasopressor is started.
Any port in a storm.
If a patient who needs vasopressors remains hypotensive while waiting for a central line to be placed, they may develop organ damage from the prolonged hypotension. When using vasopressors in a peripheral line, choose a small bore IV in the largest vein possible. If the need for vasopressors persists, a central line can then be considered. In a Cochrane review the average infusion duration of peripheral vasopressors that resulted in complications was 55 hours, which should be more than enough time to decide if a central line is needed.
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