Episode 13- “Clot Busters:” Part 2: Cardiac arrest
Black Hills, South Dakota
In Part 2 of 2 of our “Mini Grand Rounds” series, we discuss the use of thrombolytics in the setting of cardiac arrest and wrap it up with our final recommendations.
“Clot Busters: Cardiac arrest:
– Coronary artery disease is the most common cause of cardiac arrest (56-88%), and massive pulmonary embolism (PE) may account for 10% of unexplained cardiac arrests
– Multiple studies have researched thrombolytics such as alteplase (t-PA) in cardiac arrest. These studies used different doses and agents in a wide array of patient populations with varying results
– However, there is some data and expert opinion stating that t-PA may be most useful in patients who have a high likelihood PE as the cause of their cardiac arrest
– This includes patients who: are critically ill and have a history of or symptoms of PE, patients with PEA as the initial rhythm, and those with point-of-care ultrasound showing right ventricular dilation in the absence of left ventricular distention
– Also, a “triad” of: witnessed cardiac arrest, age < 65-70 years, and PEA as the initial rhythm has been shown to be associated with cardiac arrest secondary to PE. 50% of patients that fulfilled this triad had PE proven on autopsy
– The 2010 ACLS guidelines recommend not routinely administering t-PA in cardiac arrest, unless PE is presumed or known to be the cause
– A reasonable dosing strategy is to administer a flat 50 mg bolus dose for patients weighing >/= 70 kg, and to use a dose of 0.6 mg/kg (with a max of 50 mg), for patients weighing < 70 kg. This can be repeated in 15-30 minutes. Remember to continue CPR for at least 15 minutes if t-PA is given
Lederer W, Lichtenberger C, Pechlaner C, et al. Recombinant tissue plasminogen activator during cardiopulmonary resuscitation in 108 patients with out‐of‐hospital cardiac arrest. Resuscitation. 2001; 50(1): 71-76
Abu-Laban RB, Christenson JM, Innes GD, et al. Tissue plasminogen activator in cardiac arrest with pulseless electrical activity. N Engl J Med. 2002; 346: 1522-8
Comess KA, DeRook FA, Russell ML, et al. The incidence of pulmonary embolism in unexplained sudden cardiac arrest with pulseless electrical activity. Am J Med. 2000; 109: 351-6
Courtney DM, Kline JA. Prospective use of a clinical decision rule to identify pulmonary embolism as likely cause of outpatient cardiac arrest. Resuscitation. 2005; 65: 57-64
Neumar RW, Otto CWL MS, Kronik SI, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010; 122: S729-67
Welcome to part 2 of 2 of our “Clot Busters” Mini Grand Rounds series. In this episode, we discuss the use of thrombolytics in the setting of cardiac arrest. Last week, we discussed the mechanisms of action of thrombolytics and discussed their use in the setting of massive and submassive pulmonary embolism (PE). If you missed the first episode, I highly encourage you to go back and listen to that episode prior to joining us for this week’s discussion.
Coronary artery disease is the most common cause of cardiac arrest, typically due to massive MI or ischemia-related arrhythmias (56-88% of cases). Massive PE may account for 10% of unexplained cardiac arrests. Think H’s and T’s during cardiac arrest: two of the T’s are cardiac or pulmonary thrombosis.
Per the package insert, alteplase is approved for acute MI. However, cardiac arrest due to suspected PE or MI is not an approved indication, and going along with that we have no dosing regimens listed for this indication. Alteplase has numerous absolute contraindications, including active bleeding, recent intracranial or intraspinal surgery, serious head trauma, intracranial conditions, severe hypertension, stroke within the previous 3 months, and bleeding diathesis (such as vitamin K deficiency, hemophilia, and DIC). Remember, although we have to be aware of these contraindications, sometimes we will not know many of these criteria during a cardiac arrest situation. There are also a number of relative contraindications that you should know, but these are not usually considered heavily in life or death situations such as cardiac arrest (and for that matter massive PE).
There are a multitude of studies that have attempted to determine if thrombolytics are effective in cardiac arrest. The studies looked at a wide array of cardiac arrest scenarios. Some looked at cardiac arrests thought to be due to MI or PE, others looked at out-of-hospital cardiac arrests, and yet others looked at all cardiac arrest cases unresponsive to initial therapy. Most of the studies used alteplase or tenecteplase and not surprisingly, the studies came to different conclusions.
For example, in 2001, Lederer et al. published a retrospective review in cardiac arrest patients with suspected cardiac origin. Alteplase was given as a 15 mg bolus followed by 85 mg over 90 minutes in 108 patients compared to 216 controls. ROSC rates were significantly better in the alteplase group compared to the control group, at 70 % vs 51%. That’s really cool. But,
In 2002, Abu-Laban et al. published a prospective, randomized, placebo-controlled trial looking at alteplase administration in 117 patients with PEA arrest unresponsive to initial therapy. The dose of alteplase in this study was a 100 mg bolus. Contrary to the first study, there was no difference in rates of ROSC, at ~ 20% each.
Of the other studies, some concluded that using thrombolytics during cardiac arrest unresponsive to standard ACLS measures was associated with increased rates of ROSC, short term survival, and neurologically intact survival to hospital discharge. Others concluded that there was no evidence that alteplase given during CPR improved ROSC or survival to hospital discharge. Interestingly, a few of these studies did conclude that their negative results cannot be generalized to highly-selected patients with cardiac arrest, particularly those with suspected or known PE, as these patients could potentially benefit most from thrombolytics.
And this is the biggest point I want to drive home during this episode: How about we give thrombolytics to patients that are most likely to benefit, in other words, patients who have a higher likelihood of PE as a cause of the cardiac arrest? This makes sense as we already know thrombolytics work in the setting of massive PE (which if you remember includes pulselessness). So, which patients are the most likely to have a PE?
Firstly, PE should be suspected in critically ill patients who have a history of or symptoms associated with PE. This includes tachypnea, chest pain, sweating, and shortness of breath. Factors with the highest association with PE include unilateral leg swelling, O2 sats < 95%, active cancer, recent immobilization or orthopedic surgery, and recent prolonged airline travel.
Secondly, patients with PEA arrest have a higher incidence of PE than do patients who present with other rhythms. So seeing this rhythm in particular should immediately have us thinking about a possible PE.
Thirdly, using point of care ultrasound to appreciate right ventricular dilation in the absence of left ventricular distention, especially in the setting of PEA, can be a sign of a PE. In one study, 64% of patients who presented with PEA and right ventricular enlargement without left ventricular distension had a PE.
In 2004, a few authors took this a step further. They wanted to create some kind of decision-making rule to try to find out which patients in cardiac arrest were likely to have PE as the cause, and might therefore benefit most from thrombolytic therapy. They found the following triad to be associated with cardiac arrest secondary to PE; a witnessed cardiac arrest, age < 65-70 years, and PEA as the initial rhythm. But even using this triad, only ~ 50% of patients had a PE on autopsy. This is still pretty much a coin flip, but without this decision tool all we know is that ~ 10% of patients with cardiac arrest have a PE, so it is better than nothing.
What do the guidelines say? The 2010 ACLS guidelines say that thrombolytics should not routinely be used in cardiac arrest. However, when PE is presumed or known to be the cause of the cardiac arrest, thrombolytic therapy can be considered both during cardiac arrest and post-ROSC. Unfortunately in 2015, thrombolytic therapy was not reviewed.
If you do choose to give alteplase during cardiac arrest, which dose should you use? Studies used a 50 mg bolus, a 100 mg bolus, a 15 mg bolus followed by and 85 mg infusion over 90 minutes, or weight-based dosing with a max of 100 mg. So, we can conclude that the effective dose of alteplase is somewhere between 50-100 mg given as an infusion or a bolus. As a matter of fact, the 2019 European Society of Cardiology does list a dose of 0.6 mg/kg (with a max of 50 mg) over 15 minutes in the setting of cardiac arrest or massive PE. Therefore at my site, we recommend a dose of 50 mg as an IV push in patients weighing >/= 70 kg, and a weight-based dose of 0.6 mg/kg (with a max of 50 mg) in patients weighing < 70 kg. This dose can be repeated in 15-30 minutes. If you recall from Part 1, we use the same dose in the setting of massive PE. Also remember that if you do give alteplase, you should continue CPR for at least 15 minutes to ensure it has enough time to circulate and bring about ROSC prior to terminating efforts.
In conclusion of this Grand Round series, we have learned that administering thrombolytics in the setting of massive PE is highly recommended. However, in the setting of submassive PE or cardiac arrest, the use of these agents is more controversial and we have to weigh risks vs benefits on a case by case basis. We have also learned that, as is often the case, less drug is more. Thrombolytics have a dose-dependent risk of bleeding, so why not use the lowest-effective dose? We know that in the setting of massive and submassive PE, lower doses of alteplase are safe and effective with less bleeding rates, especially in low-weight patients. Less drug also means less cost, to both the facility and the patient. A 100 mg vial of alteplase costs around $10,000, and the 50 mg vial is half of that at $5,000. Remember that this is the wholesale price. The patient is usually charged more in the hospital to account for pharmacy and nursing times as well as other fees. We have also learned that less time is more. By that I mean in the extremely high stress situations of massive PE and cardiac arrest, we can simply push the alteplase versus giving it as an IV infusion lasting up to 2 hours.
As always, thank you for your time. I hope you found this series useful. If you have any comments or any differences in your own practice, please leave a comment on errxpodcast.com