The 2025 American Heart Association (AHA) Guidelines reviewed the use of systemic thrombolysis for cardiac arrest caused by suspected or confirmed pulmonary embolism, drawing primarily from observational studies, registry data, case series, and limited randomized trials. Alteplase is most commonly administered as a 50 mg intravenous bolus during ongoing cardiopulmonary resuscitation, with some protocols permitting a second 50 mg bolus if return of spontaneous circulation (ROSC) is not achieved; alternative regimens include 100 mg infused over 2 hours. The guidelines emphasize the importance of prolonged CPR following thrombolytic administration, with supporting data and European Society of Cardiology guidance recommending resuscitation efforts continue for at least 60 to 90 minutes after fibrinolysis. Registry-based studies suggest improved short-term survival in PE-related cardiac arrest when thrombolysis is used, although randomized trials in unselected cardiac arrest populations have not demonstrated a mortality benefit. Based on these findings, alteplase may be a reasonable option in PE-induced cardiac arrest, particularly when used with rapid bolus dosing and extended resuscitation, although the overall quality of evidence remains low and further PE-specific studies are needed. [1]
The 2021 European Resuscitation Council Advanced Life Support guidelines do not specify an alteplase dose for pulmonary embolism–related cardiac arrest but recommend considering thrombolytic therapy when pulmonary embolism is suspected or confirmed and continuing cardiopulmonary resuscitation for 60-90 minutes after administration. This guidance is based on very low-certainty evidence summarized by the 2020 International Liaison Committee on Resuscitation, which showed no neurologic benefit, mixed survival outcomes, and inconsistent effects on return of spontaneous circulation. Consequently, thrombolytic use carries a weak recommendation, as potential benefit may outweigh bleeding risk despite limited and inconsistent data. [2]
The 2003 British Thoracic Society (BTS) guidelines recommend systemic thrombolysis as first-line therapy for massive pulmonary embolism, including cases where cardiac arrest is imminent or occurring, and state that a 50 mg intravenous bolus of alteplase may be administered during cardiopulmonary resuscitation. This dosing approach is supported by limited evidence, primarily consisting of case reports and small studies, as large randomized trials in patients with massive or arrest-related pulmonary embolism are not feasible. The guidelines cite reports of return of spontaneous circulation within minutes of alteplase administration during CPR and acknowledge that survival, while uncommon, has been documented in otherwise fatal presentations. Given the extremely high mortality associated with massive pulmonary embolism and circulatory collapse, the BTS concludes that empiric alteplase bolus dosing is reasonable despite low quality evidence, as the potential life-saving benefit is judged to outweigh the risk of bleeding in this setting. [3]
A 2021 publication evaluated the use of recombinant tissue plasminogen activator (rtPA), specifically alteplase, in the context of circulatory arrest induced by pulmonary embolism (PE). This study contended that while current guidelines recommend a 100 mg/2 h regimen of rtPA for hemodynamic instability, this approach is not suitable for circulatory arrest scenarios owing to altered pharmacokinetics during cardiopulmonary resuscitation (CPR). The authors argued in favor of an accelerated regimen cited in the 2019 ESC/ERS Guideline of 0.6 mg/kg over 15 minutes, with a maximum dose of 50 mg, based on the rationale that the low-flow state during CPR affects the metabolism and distribution of alteplase, extending its half-life. To support this perspective, the authors conducted a thorough review of the existing literature, identifying limited studies directly comparing the accelerated regimen to standard care in circulatory arrest scenarios. Retrospective analyses, such as the 2016 PEAPETT trial, demonstrated high rates of return of spontaneous circulation (ROSC) and survival using the accelerated regimen without significant bleeding complications. In patients with massive or submassive PE without circulatory arrest, the accelerated regimen showed a trend toward fewer bleeding events compared to the two-hour regimen, as noted in a meta-analysis including a 2010 study by Wang et al. These findings collectively provide a compelling argument for using the accelerated alteplase infusion in the unique setting of PE-induced circulatory arrest. [4]
The use of thrombolysis during cardiac arrest is typically performed when there is a known or highly suspected etiology of thrombosis causing the arrest. Yet there is great variability in the use and dose of thrombolytic agents. In a 2010 article, two controlled clinical studies were identified that used alteplase for resuscitation in cardiac arrest. However, neither cases strictly observed a 100 mg intravenous (IV) push dose. The first study used alteplase administered as 50 mg IV push followed by 5000 U of heparin in cardiac arrest patients who failed standard resuscitation, while the second study administered alteplase 100 mg over 15 minutes for out-of-hospital cardiac arrest patients. IV push is typically defined as administration over 5 minutes so while the 15 minute dose rate is shorter than usual, it may not be considered an IV push. Furthermore, neither studies were able to report a statistically significant mortality benefit. Although the first study reported more patients attaining return to spontaneous circulation in the alteplase plus heparin group (68% vs 44%, p= 0.026), patient survival 24 hours after the arrest was not significantly different compared to control (35% vs 22%; p= 0.171). Similarly, the second study only observed 1 of the 233 patients enrolled in the study surviving to discharge. Nevertheless, the authors of the review still suggest thrombolysis may be beneficial if pulmonary embolism-induced cardiac arrest is suspected, followed by 15 minutes of continued cardiac pulmonary resuscitation to allow time for the medication to act. [5], [6], [7]
In a 2019 retrospective cohort study, a small number of patients were enrolled to characterize the administration method of alteplase for presumed or confirmed pulmonary embolism during cardiac arrest. Patients received alteplase either by bolus only (mean bolus dose 53.3 mg; mean cumulative dose 62.5), infusion only (mean infusion dose 87.5 mg; mean cumulative dose 76.3 mg), or bolus with infusion administration (mean bolus dose 32.7 mg; mean infusion dose 64.5 mg; mean cumulative dose 99 mg). In the bolus-only group, the majority of patients received alteplase 50 mg (range 15-100 mg); limited details are available regarding the patients who received alteplase 100 mg bolus. The mean time from cardiac arrest to onset of alteplase administration was 15.1 minutes in the bolus-only group, 46.4 minutes in the infusion-only group, and 48 minutes in the bolus with infusion group (p= 0.006). Only 2 of 16 patients in the bolus group survived to hospital discharge compared to 1 of 8 patients in the infusion-only group and 8 of 11 patients in the bolus with infusion group. There was no indication that a 100 mg bolus dose was more effective than other regimens. However, cumulative doses of alteplase were found to be significantly higher in patients who returned to spontaneous circulation (ROSC), but the small patient population limits the reliability of the results. Within their discussion, the authors note the lack of specific guideline recommendations for thrombolytic dosing, while the literature reports various dosing strategies without a clear consensus for the best dosing strategy. [8]
A multicenter, retrospective study published in 2021 evaluated the use of thrombolysis in cardiac arrest secondary to suspected or confirmed pulmonary embolism (PE). Of 47 patients who were identified to have an order for alteplase or tenecteplase, 20 were excluded due to post-ROSC thrombolysis. Thrombolytic therapy was utilized in 27 patients for pericardiac arrest with a suspected or confirmed PE. Of 11 patients who achieved ROSC, the most common dosing strategy was alteplase 100 mg (5 of 11 patients) and alteplase 50 mg (5 of 11 patients); the remaining patient received tenecteplase. It was specified that no patients received sequential boluses following the initial bolus. The authors discuss a previous international survey of thrombolytic use in cardiac arrest secondary to PE in which the most common regimen was alteplase 50 mg IV push, with the ability to repeat in 10 to 30 minutes if ROSC was not achieved. However, the survey does not describe whether an additional bolus was given following the achievement of RSOC. [9], [10]