Pulmonary Embolism During Resuscitation: Thrombolysis Under CPR

Pulmonary embolism is one of the potentially reversible causes of cardiac arrest and thus holds a special position within the ACLS algorithm. While most causes of cardiac arrest are managed under standardized CPR, fulminant pulmonary embolism requires specific causal therapy: systemic thrombolysis. The decision to administer thrombolysis during ongoing resuscitation is complex – it demands rapid clinical assessment, weighing the benefits against bleeding risk, and the willingness to significantly extend the resuscitation period. This article examines the indications, practical implementation, dosing regimens, and the available evidence for this life-saving yet high-risk intervention.

Pulmonary Embolism as a Reversible Cause in Cardiac Arrest

The AHA guidelines structure the search for causes of cardiac arrest according to the so-called H's and T's. Thromboembolism – both coronary and pulmonary – is one of the classic T-causes. Fulminant pulmonary embolism leads to acute right ventricular obstruction, resulting in reduced pulmonary blood flow, decreased left ventricular preload, and ultimately obstructive shock progressing to pulseless electrical activity (PEA) or asystole.

Epidemiologically, pulmonary embolism is estimated to be the cause in approximately 2–10% of all out-of-hospital cardiac arrests and in up to 5–13% of in-hospital resuscitations. The true incidence is likely higher, as diagnosis under resuscitation conditions is difficult and many cases are only identified at autopsy.

Why Is Pulmonary Embolism a Particular Challenge?

Unlike other reversible causes such as hypoxia or hyperkalemia, standard therapy alone (epinephrine, defibrillation for shockable rhythms) is insufficient for hemodynamically significant pulmonary embolism. The mechanical occlusion of the pulmonary arteries can only be resolved through causal therapy – thrombolysis, surgical embolectomy, or interventional catheter-based procedures. Since the latter two options are not immediately available in most settings during ongoing CPR, systemic thrombolysis remains the most important and most rapidly deployable therapeutic option.

Diagnosis Under Resuscitation Conditions

Diagnosing pulmonary embolism during ongoing CPR is inherently challenging. The gold standard imaging modality (CT angiography) is rarely available in this situation. The decision to administer thrombolysis is therefore frequently based on a clinical suspicion.

Clinical Indicators of Pulmonary Embolism as the Cause

The following factors should raise suspicion for pulmonary embolism as the cause of cardiac arrest:

• History: known deep vein thrombosis, recent immobilization, long-haul flight, postoperative state, malignancy, pregnancy/postpartum period, oral contraception, known thrombophilia
• Clinical course prior to arrest: acute dyspnea, chest pain, tachycardia, hypotension, syncope – followed by rapid circulatory collapse
• Initial rhythm: PEA is the most common initial rhythm in pulmonary embolism-associated cardiac arrest; asystole or VF/pVT are less common
• Capnography: persistently low end-tidal CO₂ values (etCO₂) despite adequate CPR may indicate reduced pulmonary blood flow

Point-of-Care Echocardiography

Transthoracic echocardiography (TTE) during CPR can provide valuable clues:

• Right ventricular dilation (RV/LV ratio > 1)
• Paradoxical septal motion (D-sign)
• Reduced or absent RV contractility
• Direct thrombus visualization in the right atrium, right ventricle, or proximal pulmonary artery trunk
• Collapsed left ventricle with reduced filling

Important: Echocardiography during CPR should be integrated in a standardized manner during rhythm check pauses to minimize interruptions to chest compressions. A negative echocardiography does not rule out pulmonary embolism.

Indications for Thrombolysis Under CPR

The decision to administer systemic thrombolysis during ongoing resuscitation is one of the most demanding clinical decisions in the emergency setting. It is a therapy with significant bleeding risk, but in cases of confirmed or highly probable pulmonary embolism as the cause of cardiac arrest, it may offer the only realistic chance of ROSC (Return of Spontaneous Circulation).

When Is Thrombolysis Indicated?

According to AHA and ERC recommendations, systemic thrombolysis under CPR should be considered in the following situations:

• Confirmed pulmonary embolism as the cause of cardiac arrest (e.g., known thrombosis with acute decompensation, thrombus detected on echocardiography)
• High clinical suspicion of pulmonary embolism (typical history + PEA arrest + echocardiographic signs of right heart strain)
• Differential diagnostic consideration: When other reversible causes have been excluded or are unlikely and the overall clinical picture is consistent with pulmonary embolism

When Is Thrombolysis Under CPR Contraindicated or Not Recommended?

• No thrombolysis for unclear arrest etiology without evidence of pulmonary embolism: Routine empirical thrombolysis in cardiac arrest without suspicion of pulmonary embolism or myocardial infarction is not recommended based on current evidence. The TROICA trial (tenecteplase vs. placebo in undifferentiated cardiac arrest) showed no survival benefit with untargeted administration.
• Absolute contraindications (to be considered relative in a resuscitation situation): active intracranial hemorrhage, recent severe traumatic brain injury, recent neurosurgical procedures. In practice, when facing an otherwise non-survivable cardiac arrest with high suspicion of pulmonary embolism, the risk-benefit assessment will frequently favor thrombolysis – as the alternative is death.

Dosing and Practical Implementation

Alteplase (rt-PA) – The Standard Therapeutic Agent

Alteplase is the most commonly used and best-studied fibrinolytic agent under CPR for pulmonary embolism. The recommended dosing regimen:

• Total dose: 50 mg alteplase as an intravenous bolus
• Alternatively, some protocols recommend a split dose: 50 mg bolus, followed by an additional 50 mg over 60 minutes (total dose 100 mg)
• In the resuscitation setting, the 50 mg bolus is often preferred, as a controlled infusion is difficult to manage during CPR and rapid onset of action is critical

Tenecteplase as an Alternative

Tenecteplase offers the advantage of a weight-adjusted single bolus dose and is preferred in some centers:

• Weight-adjusted dosing:
  • < 60 kg: 30 mg (6,000 IU)
  • 60–69 kg: 35 mg (7,000 IU)
  • 70–79 kg: 40 mg (8,000 IU)
  • 80–89 kg: 45 mg (9,000 IU)
  • ≥ 90 kg: 50 mg (10,000 IU)
• Advantage: simple administration, no infusion required, rapid bolus

Accompanying Measures

• Heparin: Concomitant administration of unfractionated heparin (UFH) as a bolus (e.g., 5,000–10,000 IU i.v.) is recommended in many protocols to prevent rethrombosis. The exact timing (before, simultaneously, or after thrombolysis) is not uniformly standardized; pragmatic simultaneous administration is common practice.
• Epinephrine: Epinephrine administration as part of the ACLS algorithm is continued. Note that after successful thrombolysis, ROSC may occur with potentially significant hemodynamic instability.
• CPR quality: High-quality chest compressions are particularly critical during thrombolysis – they are the only mechanism that ensures transport of the thrombolytic agent to the thrombus.

Extended Resuscitation Duration After Thrombolysis

A central and often overlooked aspect of thrombolysis during CPR is the need for extended resuscitation duration after administration of the fibrinolytic agent.

Why Continue Resuscitation for an Extended Period?

• The effect of alteplase and tenecteplase does not occur immediately. The enzymatic dissolution of the thrombus requires time – the maximum fibrinolytic effect is not reached until 60–90 minutes.
• If resuscitation is terminated shortly after thrombolytic administration, the medication has no chance to take effect. The administration would then have been futile.
• Continued chest compressions maintain the minimal pulmonary blood flow necessary to transport the fibrinolytic agent to the thrombus.

Recommended Resuscitation Duration After Thrombolytic Administration

The AHA and ERC guidelines recommend:

• At least 60–90 minutes of CPR after administration of the thrombolytic agent before termination of resuscitation is considered
• This applies regardless of whether ROSC was achieved and subsequently lost in the interim
• Extended resuscitation places significant demands on the team: personnel resources, rotation of chest compressions, psychological burden

Practical Challenges

• Team communication: All team members must be informed that thrombolysis has been administered and that extended resuscitation is therefore planned. This must be clearly communicated and documented.
• Staffing: With an expected resuscitation duration of 60–90 minutes after thrombolytic administration, a sufficient number of providers must be planned for chest compressions (rotation every 2 minutes).
• Bleeding complications: Significant bleeding may occur during ongoing thrombolysis and CPR (access sites, thoracic trauma from compressions). Careful monitoring is necessary.

Evidence and Outcome Data

The evidence for thrombolysis during CPR for pulmonary embolism is derived predominantly from observational studies, case series, and registry data. Randomized controlled trials in this specific population are barely feasible for ethical and logistical reasons.

Key Study Data

• Registry data and meta-analyses show that systemic thrombolysis in pulmonary embolism-associated cardiac arrest can significantly improve ROSC rates and hospital survival. Some analyses have reported ROSC rates exceeding 50% and survival-to-hospital-discharge rates of 15–20% – significantly higher than in comparable patients without thrombolysis.
• Systematic reviews show a consistent trend favoring thrombolysis when there is a well-founded suspicion of pulmonary embolism as the arrest etiology, with a relative survival advantage over standard CPR alone.
• TROICA trial: This prospective, randomized trial evaluated tenecteplase vs. placebo in undifferentiated cardiac arrest (without targeted suspicion of pulmonary embolism). No significant survival benefit was demonstrated in the overall population – a finding that underscores the importance of targeted indication. However, the subgroup analysis of patients with suspected pulmonary embolism showed a trend favoring thrombolysis.
• Neurological outcome: The available data suggest that survivors of pulmonary embolism-associated resuscitation with thrombolysis frequently have acceptable neurological outcomes (CPC 1–2), which is remarkable given the prolonged resuscitation duration.

Limitations of the Evidence

• Selection bias in observational studies (patients who received thrombolysis may have had more favorable baseline conditions)
• Heterogeneous protocols (dosing, timing, concomitant therapies)
• Lack of large randomized trials specifically for the population "pulmonary embolism + cardiac arrest"
• Difficulty of definitive diagnosis during CPR

Algorithm: Approach When Pulmonary Embolism Is Suspected During CPR

In summary, the following structured approach can be recommended:

1. Initiate standard ACLS algorithm (high-quality CPR, airway management, rhythm analysis, epinephrine)
2. Evaluate reversible causes (H's and T's) – specifically search for indicators of pulmonary embolism
3. Formulate clinical suspicion: history, risk factors, initial rhythm (PEA?), low etCO₂
4. Point-of-care echocardiography during rhythm check pauses: signs of right heart strain?
5. Decision to administer thrombolysis when there is high suspicion or confirmed pulmonary embolism:
   • Alteplase 50 mg i.v. bolus (optionally followed by 50 mg over 60 min) or tenecteplase weight-adjusted as bolus
   • Consider concomitant UFH bolus
6. Continue CPR for at least 60–90 minutes after thrombolytic administration
7. Team communication: Clear announcement to the entire team, documentation of thrombolysis timing
8. Upon ROSC: close hemodynamic monitoring, continue anticoagulation, aim for CT angiography for confirmation, transfer to intensive care unit
9. After ROSC: Evaluate further therapeutic options (interventional catheter-based therapy, surgical embolectomy) depending on residual thrombus burden and clinical course

Special Situations

Pregnancy

Pulmonary embolism is one of the most common causes of maternal mortality. Systemic thrombolysis is also indicated during pregnancy under resuscitation conditions when fulminant pulmonary embolism is suspected as the cause. Fetal risk is secondary to maternal survival. Alteplase does not cross the placenta to a clinically relevant extent.

Prehospital Thrombolysis

The decision to administer thrombolysis can also be made in the prehospital setting when there is a well-founded suspicion of pulmonary embolism as the arrest etiology. The availability of fibrinolytic agents on emergency physician response vehicles varies by EMS system. The decision should ideally be made by experienced emergency physicians and clearly documented.

eCPR and Interventional Options

In specialized centers, extracorporeal CPR (eCPR) using VA-ECMO is increasingly available as a bridging option. This enables hemodynamic stabilization and provides time for interventional catheter-based thrombus removal. However, these options are limited to select centers and require appropriate infrastructure.

Key Messages

• Pulmonary embolism is a reversible cause of cardiac arrest – it must be actively sought
• Systemic thrombolysis under CPR is indicated when there is high suspicion or confirmed pulmonary embolism as the arrest etiology
• Alteplase 50 mg bolus or weight-adjusted tenecteplase are the standard options
• After thrombolytic administration, CPR must be continued for at least 60–90 minutes
• The evidence shows a consistent survival benefit with targeted indication
• Routine empirical thrombolysis in undifferentiated cardiac arrest is not recommended
• Point-of-care echocardiography is a valuable diagnostic tool during CPR

Practical Training

The decision to administer thrombolysis during ongoing resuscitation is a situation that rarely occurs in clinical practice but demands the highest level of decision-making confidence and structured teamwork when it does. In the ACLS courses offered by Simulation Tirol, precisely these complex scenarios are simulated in a hands-on manner – including cause identification, integration of point-of-care ultrasound, thrombolysis decision-making, and extended team-based resuscitation. The opportunity to practice this rare but life-saving therapy in a safe learning environment and internalize the workflows can make the decisive difference in a real emergency.