Thrombolytics for the Coding Patient

Managing a cardiac arrest is the paramount skill of an emergency medicine physician. The process is a furious loop of assessments, actions, and decisions. Choices are often made with minimal information to fall back on, and delays of mere seconds can define the outcome. When running the rapid mental checklist of Hs and Ts, the decision to give or withhold thrombolytics is one that is often made amidst a fog of uncertainty. And while the benefit may be a life saved, the risks are very real, and the consequences extend far past the point of return of spontaneous circulation (ROSC).

Guidelines and Gestalt

The evidence for the use of thrombolysis in cardiac arrest is thin and far from definitive.

A 2020 ILCOR systematic review confirmed that no large RCTs exist that have evaluated the use of thrombolytics in cardiac arrest due to a suspected PE. Some observational data and case series suggest a possible benefit, but they are marred by major biases. One case series reported ROSC in 20/23 patients given TPA, but there was no control group to compare.

According to current ACLS guidelines and the AHA, the use of thrombolytics may be considered in cardiac arrest when PE is presumed, though this is with a 2b recommendation, which is not exactly the strongest level of evidence.

While some case studies show possible benefits of other interventions, such as mechanical thrombectomy vs surgical embolectomy, the feasibility of these options will depend heavily on the availability of these services with very short notice and the need for buy-in from multiple departments. While these may not be realistic options for many hospital systems, it is at least worth a discussion with all stakeholders.

Ultimately, the decision comes down to the clinician looking at the patient in front of them, and weighing the risks and benefits of thrombolytics:

• Is the clinical suspicion for PE high?

• What is the risk of bleeding?

• How likely is it that thrombolytics will change the outcome?

• Is the patient young and healthy with a high likelihood of meaningful recovery?

• Is the patient elderly, or do they have significant comorbid conditions that would likely result in a poor prognostic outcome?

Dosing, CPR Duration, and Post-ROSC Care

You have made the decision to administer thrombolytics: how much do you give, and how long do you continue CPR to let the medication circulate?

• Alteplase - 50mg IV push, which can be given peripherally or through an IO. After administration, continue CPR for at least 15 minutes.

• Tenecteplase - Weight-based dose between 30-50 mg, and CPR should be continued for at least 30 minutes.

• Consider the use of a mechanical CPR device.

Patients who achieve ROSC following thrombolytics may initially appear stable, then quickly deteriorate. This can be due to a myriad of factors. They may be in obstructive or cardiogenic shock from their clot burden. They may be developing a critical bleeding issue such as abdominal/thoracic hemorrhage, cardiac tamponade, a mediastinal hematoma, or an intracranial hemorrhage. They may have an anoxic brain injury from their arrest.

Start by resuscitating the patient, getting a full set of labs, and then reach for your ultrasound. Perform a bedside RUSH to evaluate for any obvious signs of LV/RV dysfunction, tamponade, or bleeding in the chest, abdomen, or pelvis.

If there is no clear source of decompensation identified by POCUS, consider CT imaging to get a clearer picture of what might be going on. Obviously, these patients are going to be quite unstable, but at this point, there may not be another option besides CT to identify the cause of the instability.

Time to Throw it in Reverse

While thrombolytics have a fairly short half-life, the fibrinolytic effects can last for many hours. For post-lytic patients with a high suspicion of bleeding, consider starting reversal agents in the ED if the patient is showing signs of major bleeding. Most hospitals will have several options available for treatment:

• First, stop all anticoagulants and TPA infusion

• Cryoprecipitate: 10 units IV; aim for a fibrinogen level of >150 mg/dL

• TXA: Give 1–2 g IV to inhibit fibrinolysis

• Platelets: For thrombocytopenia; target a platelet level of>100k

• FFP: Contains coagulation factors but can be a high-volume infusion, so use cautiously in RV failure

• Kcentra (PCC): Preferred for rapid reversal — contains factors II, VII, IX, X

• Factor VII: Optional, used off-label in some scenarios

Keep Calm, and Carry On

The evidence is vague, and often the clinical picture is even cloudier at a time when clarity is needed most. The patient's story and your clinical gestalt will guide your decisions during these critical moments. If you decide to initiate thrombolytics, remember to commit to the proper amount of time for CPR and use a mechanical device if available. Post-ROSC instability should be aggressively investigated with ultrasound and/or CT imaging. The use of reversal agents should be targeted and timely when signs of massive bleeding are evident.

If you want to dig deeper, listen to this month’s ERcast podcast episode, “Thrombolytics for the Coding Patient,” as Tim Montrief, MD, sits down with Dr. Matt Delaney to unpack a real case of thrombolytics in cardiac arrest—and the complications that followed.