Considerations for Combining Therapeutic Hypothermia and PCI in STEMI Patients

There is a growing body of evidence that therapeutic hypothermia (TH) in patients who are comatose after cardiac arrest improves neurologic outcomes.^1,2 This is an exciting addition to traditional percutaneous coronary intervention (PCI) therapy for ST-elevation myocardial infarction (STEMI) patients, since brain injury is the ultimate cause of death in 68% of patients who are resuscitated out-of-hospital but die before discharge.³ Enloe Medical Center, a 298-bed hospital in northern California, had an existing hypothermia protocol, but concerns were raised when patients would present with an arrest that left them unconscious, and they needed a heart cath. Is combining these therapies safe and effective? In the first 90 minutes, which should take precedence? How do you make the staff comfortable and competent with using TH during a PCI? What additional considerations are there when these therapies are combined?

The literature does support the combination of PCI and TH.^5-10 With the addition of TH, it is possible to not only save patients’ lives but to have favorable neurologic outcomes as well. One study found patients who received TH before, during, or immediately after PCI did have a significant improvement in neurologic outcomes, compared to those who did not receive TH.¹¹ Another study treated patients with PCI and then TH if they were still comatose after the procedure, and found that 68% of these patients had a favorable neurologic outcome.⁷ In a third study, 56% of patients who underwent PCI and TH had favorable outcomes compared to 26% who were treated with neither.⁹ Yet another study found a trend towards improved neurologic outcomes, although this was not found to be statistically significant.¹⁰ It is also possible that adding TH may reduce infarct size if started before PCI.^5,6

But even though the evidence indicated this was a safe and effective therapy, there was still some reluctance to perform PCI on hypothermia patients, or hypothermia on STEMI patients. We had to get buy-in from the staff. We created separate training programs for different units. Emergency room staff and cath lab staff received in-services with hands-on training regarding which patients are appropriate for this therapy, how this therapy can change lives, how to set up equipment, and what to monitor in the initial stages. The ICU training was also hands on, but more focused on the physiologic changes of hypothermia, the importance of adequate sedation, and how to re-warm patients appropriately. The existing protocol was reviewed with both sets of staff. 

We found that the method of cooling needed to be compatible with performing a heart cath right away. This meant that the equipment needed to be portable, quick to set up, radiolucent, and provide access to the groin areas and to the chest in case defibrillation was needed. Enloe already had the Blanketrol (programmable body temperature regulation) (Cincinnati Sub Zero, CSZ Medical) for hypothermia patients, and we decided to use the Gelli-Roll (a reusable warming and cooling gel pad) (Cincinnati Sub Zero, CSZ Medical) whenever TH was initiated in the ER or cath lab. The Gelli-Roll can be set up ahead of time, can be transferred with the patient, and it leaves the chest and groin areas free. The drawback of this system is that the unit must be off or in standby while images are taken; however, it does stay cold for the time it takes to perform the procedure.

Our cooling protocol includes giving a 20ml/kg bolus of 4°C normal saline. During staff training, we realized that some of the staff had concerns with giving a large fluid bolus to patients who had a compromised heart. By reviewing the literature, we were able to reassure nurses that cold fluid boluses were used in many trials without adverse affect, and may improve hemodynamic stability by preventing hypovolemia.¹²

We also had to decide which method of temperature monitoring we would use. We considered esophageal monitoring, but it would have required extra training on inserting the esophageal probe, and there was the risk of dislodgement while transferring the patient. We decided to use bladder temperature monitoring, since it would require no extra training and the risk of dislodgement was lower. The staff was educated that the bladder temperature might not be as accurate if urine output is very low.¹³

Then there was a question of timing and prioritization. TH “should probably be initiated as soon as possible after return of spontaneous circulation but appears to be successful even if delayed (e.g. 4-6 hours)”.¹⁴ For patients with STEMI, the American College of Cardiology (ACC) and American Heart Association (AHA) recommend PCI within 90 minutes of presentation to a facility, and encourages even faster times.¹⁵ One study found that adding TH did not result in delays of PCI past 90 minutes.¹⁰

In practice, it is hard to say which therapy should be started first every time. If the cath lab team needs to be called in, it makes sense to start the TH while the team is arriving. Or, if the team is ready to go, it may make sense to do the procedure and then start TH afterwards. Either way, everything should be done to ensure the PCI is completed within 90 minutes and the TH is started as soon as possible, either before or after PCI.

Adding TH does increase the need for monitoring. Temperatures below the target temperature may result in increased complications, and above the target temperature may provide less neuroprotective benefits.¹⁶ In the initial stages, TH is associated with arrhythmias (particularly bradycardia), hyperglycemia, and fluid and electrolyte disturbances.¹⁷ If the cath lab did not have extra staff, such as in off hours, we decided the House Supervisor would provide an extra RN trained in TH. This RN would be responsible for setting up equipment, monitoring the temperature, ensuring adequate sedation, and checking and replacing electrolytes as necessary.
After the procedure, patients who have received both therapies are at increased risk for bleeding complications and infection.^18,10 However, there does not seem to be an increase in need for vasopressors and inotropes, intra-aortic balloon pump (IABP), or repeat cardioversion or defibrillation.¹¹ TH can decrease the effectiveness of clopidogrel¹⁹, so these patients should have routine 12-lead ECGs to monitor for subacute in-stent thrombosis.¹¹  

TH can seem daunting, especially since patients who have suffered cardiac arrest are so critically ill. But adding TH to an existing STEMI program is an opportunity to save lives and preserve brain function.

Laura Schiff can be contacted at lauragaap@hotmail.com.

References

1. Hypothermia After Cardiac Arrest Study Group (HACA). Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002 Feb 21; 346(8): 549-556.
2. Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002 Feb 21; 346(8): 557-563.
3. Deaken CD, Nolan JP, Soar J, Sunde K, Koster RW, Smith GB, Perkins GD. European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. Resuscitation 2010; 81: 1305-1352. doi:10.1016/j.resuscitation.2010.08.017.
4. Batista LM, Lima FO, Januzzi JL, Donahue V, Snydeman C, Greer DM. Feasibility and safety of combined percutaneous coronary intervention and therapeutic hypothermia following cardiac arrest. Resuscitation 2010; 81: 398-403. doi:10.1016/j.resuscitation.2009.12.016
5. Dixon SR, Whitbourn RJ, Dae MW, Grube E, Sherman W, et al. Induction of mild systemic hypothermia with endovascular cooling during primary percutaneous coronary intervention for acute myocardial infarction. J Am Coll Cardiol 2002 Dec 4; 40(11): 1928-1934. 
6. Götberg M, Olivecrona GK, Koul S, Carlsson M, Engblom H, et al. A pilot study of rapid cooling by cold saline and endovascular cooling before reperfusion in patients with ST-elevation myocardial infarction. Circ Cardiovasc Interv 2010 Oct; 3(5): 400-407.
7. Hovdenes J, Laake JH, Aaberge L, Haugaa H, Bugge JF. Therapeutic hypothermia after out-of-hospital cardiac arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock. Acta Anaesthesiol Scand 2007 Feb; 51(2): 137-142.
8. Kandzari DE, Chu A, Brodie BR, Stuckey TA, Hermiller JB, Vetrovec GW, et al. Feasibility of endovascular cooling as an adjunct to primary percutaneous coronary intervention (results of the LOWTEMP pilot study). Am J Cardiol 2004 Mar 1; 93(5): 636-639.
9. Sunde K, Pytte M, Jacobsen D, Mangschau A, Jensen LP, Smedsrud C, Draegni T, Steen PA. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 2007 Apr; 73(1): 29-39.
10. Wolfrum S, Pierau C, Radke PW, Schunkert H, Kurowski V. Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute ST-segment elevation myocardial infarction undergoing immediate percutaneous coronary intervention. Crit Care Med 2008; 36(6): 1780-1786. 
11. Knafelj R, Radsel P, Ploj T, Noc M. Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction. Resuscitation 2007; 74: 227-234. doi:10.1016/j.resuscitation.2007.01.016
12. Polderman K, Herold I. Therapeutic hypothermia and controlled normothermia in the intensive care unit: practical considerations, side effects, and cooling methods. Crit Care Med 2009; 37(3): 1101-1120.
13. Knapik P, Rychlik W, Duda D, Golyszny R, Borowik D, Ciesla D. Relationship between blood, nasopharyngeal and urinary bladder temperature during intravascular cooling for therapeutic hypothermia after cardiac arrest. Resuscitation 2012 Feb; 83(2): 208-212. doi:10.1016/j.resuscitation.2011.09.001
14. Nolan JP, Morley PT, Vanden Hoek TL, Hickey RW, et al; International Liaison Committee on Resuscitation. Therapeutic hypothermia after cardiac arrest: an advisory statement by the advanced life support task force of the International Liaison Committee on Resuscitation. Circulation 2003 Jul 8; 108(1): 118-121.
15. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol 2004 Aug 4; 44(3): E1-E211.
16. Finley Caulfield A, Rachabattula S, Eyngorn I, Hamilton SA, et al. A comparison of cooling techniques to treat cardiac arrest patients with hypothermia. Stroke Res Treat Article ID 690506, 6 pages, 2011. doi:10.4061/2011/690506.
17. Lee R, Asare K. Therapeutic hypothermia for out-of-hospital cardiac arrest. Am J Health Syst Pharm 2010 Aug; 67(15): 1229-1237.
18. Nielsen N, Sunde K, Hovdenes J, Riker RR, Rubertsson S, Stammet P, et al. Adverse events and their relation to mortality in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia. Crit Care Med 2011 Jan; 39(1): 57-64.
19. Bjelland TW, Hjertner Ø, Klepstad P, Kaisen K, Dale O, Haugen BO. Antiplatelet effect of clopidogrel is reduced in patients treated with therapeutic hypothermia after cardiac arrest. Resuscitation 2010 Dec; 81(12): 1627-1631.