Stress Agents and Nuclear Lab Emergencies

By Guest Blogger Brett W. Sperry, MD
Understanding the stress agents used in the nuclear lab as well as potential emergencies and supply shortages is essential for providers who are involved in nuclear cardiology. While these concepts are some of the first that we learn when studying for a career in nuclear medicine, they can easily be forgotten in day-to-day practice. In this blog, I review some of these basic concepts for nuclear cardiologists, trainees, technologists, and others involved in the nuclear cardiology lab.

Brett W. Sperry, MD

Stress agents and imaging modalities1,2 are described below in Figure 1. Most commonly, vasodilators are used to increase blood flow to normally perfused areas of the myocardium, uncovering potential areas of decreased perfusion caused by fixed coronary stenoses. All vasodilators act through the adenosine pathway leading to vascular smooth muscle vasorelaxation.

Figure 1. Stress agents and imaging modalities. 

Adenosine directly activates the A2a receptor causing coronary vasodilation, but also activates other adenosine receptors.
  • Half-life is 2-10 seconds.
  • Off-target effects:
♦  A1 receptor: AV block, chest pain and tachypnea.
♦  A2b receptor: peripheral vasodilation (headache, diarrhea).
♦  A2b/A3 receptor: bronchospasm.
  • Protocol: continuous infusion of 140 ug/kg/min for 6 minutes, inject radiotracer at 3 minutes.
  • Contraindications: bronchospasm, hypotension, heart block. 

Regadenoson (Lexiscan): Directly activates A2a receptors with high affinity and low off-target effects causing coronary vasodilation.
  • Half-life for hyperemia is 3-5 minutes. Triphasic half-life so may have side effects of headache, chest pain, diarrhea for 15-20 minutes.
  • Off-target effects: less than adenosine.
  • Protocol: rapid injection over 10 seconds followed by saline flush. Radionuclide is injected 10-20 seconds after saline.
  • Caution: seizures, LBBB, pacemaker.

Dipyridamole (Persantine): Phosphodiesterase inhibitor that prevents intracellular reuptake of adenosine.
  • Maximal hyperemia in 15 minutes. Alpha half-life is 30-60 minutes, beta half-life 10 hours.
  • Off-target effects: Similar potential to adenosine. May have late symptoms after aminophylline reversal agents have worn off.
  • Protocol: Infusion over 4 minutes, then inject radiotracer 3-5 min after dipyridamole infusion is complete.
  • Consider using preferentially if history of seizure, pacemaker, LBBB.
The rate of side effects for vasodilator agents are seen below in Table 1.3

Table 1. Rates of Side Effects for Vasodilator Agents 

From Abidov, et al. J Nucl Cardiol. 2019.3

Reversal of vasodilators can be considered for side effects, though most are self-limiting.4 Indications for reversal include severe hypotension, 2nd- or 3rd-degree heart block, ST depression with angina, wheezing, or intolerable symptoms. Adenosine almost never requires reversal due to the short half-life. For mild symptoms, ask patient to consume coffee or diet soda after completing the test.

Options for reversal:
  • Aminophylline 50-250mg IV over 1 minute (do not give if having a seizure as this lowers the seizure threshold).
  • IV theophylline 50mg slow injection over 1 minute.
  • IV caffeine 60mg in 25mL of D5W over 3-5 minutes.
  • PO caffeine 60-160mg.


1) Bradyarrhythmia, complete heart block, asystole

Figure 2. From Derbas, et al. JACC Imaging, 2019.5

Treatment: CPR if pulseless, immediate IV aminophylline, atropine 0.5mg IV.
Important points: Bradyarrhythmias are uncommon, but are seen most often with adenosine and rarely with dipyridamole. There were no cases of high-degree AV block in the ADVANCE trial6 using regadenoson, though patients received adenosine first and were excluded if they did not tolerate it. Bradyarrhythmias with regadenoson are thought to be secondary to vagal stimulation via the A2a receptor in the hypothalamus and nucleus solitarius.

2) Wheezing, dyspnea, respiratory failure: Caused by bronchoconstriction.
Treatment: IV aminophylline, bronchodilators, airway management as needed.
Important points: Vasodilators are safe in patients with a history of COPD or asthma, but do not give vasodilators in a patient with a recent exacerbation or active wheezing. Be prepared with aminophylline and emergency equipment readily accessible.7

3) Seizure: Seen in post-marketing reports of vasodilators (predominantly regadenoson). A2a receptors in the central nervous system are implicated.
Treatment: IV benzodiazepine. Avoid reversal agents like aminophylline.

4) Sustained tachyarrhythmias: Seen in about 1% of dobutamine stress tests.8
Treatment: AV nodal blocking agents, cardioversion
Important points: About two-thirds of patients in atrial fibrillation due to dobutamine will convert to sinus rhythm within an hour.

1.  Henzlova MJ, Duvall WL, Einstein AJ, Travin MI, Verberne HJ. ASNC imaging guidelines for SPECT nuclear cardiology procedures: Stress, protocols, and tracers. J Nucl Cardiol. 2016 Jun;23(3):606-39.
2.  Dilsizian V, Bacharach SL, Beanlands RS, Bergmann SR, Delbeke D, Dorbala S, Gropler RJ, Knuuti J, Schelbert HR, Travin MI. ASNC imaging guidelines/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol. 2016 Oct;23(5):1187-226.
3.  Abidov A, Dilsizian V, Doukky R, Duvall WL, Dyke C, Elliott MD, Hage FG, Henzlova MJ, Johnson NP, Schwartz RG, Thomas GS, Einstein AJ. Aminophylline shortage and current recommendations for reversal of vasodilator stress: An ASNC information statement endorsed by SCMR. J Nucl Cardiol. 2019 Jun;26(3):1007-14.
4.  Doran JA, Sajjad W, Schneider MD, Gupta R, Mackin ML, Schwartz RG. Aminophylline and caffeine for reversal of adverse symptoms associated with regadenoson SPECT MPI. J Nucl Cardiol. 2017 Jun;24(3):1062-70.
5.  Derbas LA, Thomas GS, Medina CA, Abdel-Karim AA, Saeed IM, Bateman TM. Severe bradycardia and asystole following regadenoson in pharmacological myocardial perfusion imaging: Cases and treatment recommendations. JACC Cardiovasc Imaging. 2019 Jul;12(7 Pt 1):1288-90.
6. I skandrian AE, Bateman TM, Belardinelli L, Blackburn B, Cerqueira MD, Hendel RC, Lieu H, Mahmarian JJ, Olmsted A, Underwood SR, Vitola J, Wang W; ADVANCE MPI Investigators. Adenosine versus regadenoson comparative evaluation in myocardial perfusion imaging: results of the ADVANCE phase 3 multicenter international trial. J Nucl Cardiol. 2007 Sep-Oct;14(5):645-58.
7.  Thompson RC. Regadenoson stress in patients with asthma and COPD: A breath of fresh air. J Nucl Cardiol. 2012; 19:647-8.
8.  Sheldon SH, Askew JW, Klarich KW, Scott CG, Pellikka PA, McCully RB. Occurrence of atrial fibrillation during dobutamine stress echocardiography: Incidence, risk factors, and outcomes. J Am Soc Echocardiogr. 2011 Jan;24(1):86-90.

DISCLOSURES: Dr. Sperry has received research grants from Pfizer and consulting/speaking fees from Pfizer, Alnylam, and Novartis.

BLOGGER BIO: Dr. Brett Sperry (@BrettSperryMD) is an advanced heart failure, transplant and nuclear cardiologist at Saint Luke's Mid America Heart Institute and the Director of the Cardiac Amyloidosis Program.

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