Dipyridamole

Jean Lette M.D., F.C.C.P.; Michel Cerino M.D.; Michel Laverdiere M.D.; Jacques Tremblay M.D.; and Julie Prenovault M.D.

We describe the occurrence of sudden severe bronchospasm and respiratory arrest following dipyridamole infusion in a patient with chronic obstructive pulmonary disease predominantly of the emphysematous type. The severe reaction was unexpected because the patient had tolerated well withdrawal of aminophylline derivatives for 48 hours and was receiving chronic prednisone 20 mg qd. Although the diagnostic and prognostic gains from dipyridamole imaging far outweight the small risk associated with the test, patients with chronic pulmonary obstructive disease must be closely monitored during thallium-dipyridamole imaging.

(Chest 1989;95:1345-49)

Exercise thallium-201 myocardial scintigraphy is widely used clinically both to diagnose coronary artery disease and to evaluate the prognosis of known coronary patients.[1] In patients unable to exercise, similar scintigraphic images can be obtained following pharmacologic coronary vasodilation with dipyridamole.[2] Occasional minor side effects of dipyridamole such as headache, dizziness, noncoronary chest pain, angina (20 to 30 percent) and rarely significant hypotension, are rapidly reversed by intravenous aminophylline.[2] Considering the number of "high risk" patients who undergo such studies, surprisingly few cases of severe and irreversible side effects have been reported. Serious complications reported include severe bronchospasm, myocardial infarction, ventricular arrhythmia and cardiac arrest. In this report, we describe a patient with severe chronic obstructive pulmonary disease (COPD) predominantly of the emphysematous type, who developed acute bronchospasm and respiratory arrest following dipyridamole infusion.

CASE REPORT

A 67-year-old retired bus driver was referred for pulmonary evaluation for possible bullectomy. There was a 40-year history of chronic obstructive pulmonary disease which had deteriorated in the preceeding five years, and a six-month history of atypical chest pain considered to be angina pectoris. The patient was treated with long-acting aminophylline derivatives and salbutamol PO, ipratropium bromide (Atrovent) aerosols qid, prednisone 20 mg qd, and sublingual nitroglycerin prn. On physical examination, he was dyspneic at rest, the pulse rate was 80 and regular, the blood pressure 130/80 mm Hg, and the respiratory rate was 24. Auscultation revealed decreased air entry and a few rhonchi bilaterally. Resting ECG was normal. Chest x-ray film (Fig 1) and thoracic computed tomography (Fig 2) revealed bilateral emphysema with upper lobe predominance, a calcified granuloma in the right lower lobe, and small, calcified lymph nodes in the right hilar area. Pulmonary function tests (Table 1) showed severe COPD with low diffusion and normal blood gases as seen in emphysema. He was referred for thallium-dipyridamole imaging to clarify the nature of the chest pain. All aminophylline derivatives, coffee and tea were discontinued 48 hours prior to the test without consequent clinical deterioration of his respiratory status. The patient was stable and the auscultation unchanged prior to dipyridamole infusion. He remained asymptomatic throughout the infusion, during which he performed a handgrip exercise, with a 10 beat per minute increment in heart rate and stable blood pressure. Five minutes after the infusion of 0.56 mg/kg of dipyridamole, he rapidly developed severe dyspnea, bronchospasm which faded in intensity as air entry diminished, and central and peripheral cyanosis. Respiratory arrest followed within two minutes, despite the prompt administration of two intravenous doses of 125 mg aminophylline. The ECG monitor showed sinus rhythm with no ST-T change throughout the entire episode. The patient was immediately intubated, ventilated and transferred to the intensive care unit on hydrocortisone 2-sodium succinate (Solu-Cortef) and an aminophylline drip. The bronchospasm gradually resolved and he was extubated three hours later. Results of chest x-ray examination, serial ECGs and cardiac enzyme determinations were unremarkable. Unfortunately, this incident only confirmed the patient's mistrust of doctors, and he discharged himself from the hospital against medical advice the following day.

DISCUSSION

Thallium-dipyridamole imaging is widely used in clinical practice. Angina pectoris and noncoronary chest pain occur in 20-25 percent of patients, but are rapidly reversed with administration of aminophylline.[3,4] Severe and irreversible cardiac side effects are uncommon: there were no complications of myocardial infarction, sustained arrhythmia or death in 293 consecutive studies by Homma et al,[5] in 337 consecutive patients (including 101 over the age of 70) reported by Lam et al,[6] and 93 consecutive patients reported by Gerson et al.[7] Homma et al report one case of severe bronchospasm requiring intubation in an asthmatic patient.[5] The series of Lam et al includes one case of prolonged myocardial ischemia requiring coronary angioplasty and seven other cases of "severe ischemic response" defined as severe, recurrent or persistent chest pain lasting 15 minutes or more, all of which responded to intravenous aminophylline and sublingual nitroglycerin.[6] Isolated cases of ventricular fibrillation[8] and cardiac arrest with subsequent myocardial infarction[9] have been reported. Over 10,000 patients have undergone thallium-dipyridamole imaging as of June, 1988. Very few coronary deaths (approximately three) have been reported to date (personal communication, Dr Alan Rohansky, Boeringher Ingelheim, June, 1988). We describe the occurrence of acute bronchospasm followed by respiratory arrest in a patient with chronic obstructive pulmonary disease. Experiments on isolated rat lung suggest that such episodes may be caused by dipyridamole inhibition of pulmonary uptake of prostaglandin [E.sub.2], a bronchodilator.[10] The sudden deterioration of our patient after dipyridamole infusion seems somewhat surprising, as both the clinical examination and pulmonary function tests supported the diagnosis of chronic obstructive pulmonary disease predominantly of the emphysematous type rather than reversible small airways disease. This case demonstrates that severe bronchospasm and the need for intubation during thallium-dipyridamole imaging can occur not only in true asthmatics, but also in the whole spectrum of chronic obstructive pulmonary disease. Many centers "protect" such patients with steroids during the 48-hour aminophylline withdrawal period, but as illustrated in our case, this does not offer any guarantee that no such complication will occur. Despite these reservations, one must emphasize that thallium-dipyridamole imaging is widely used and reports of serious and irreversible cardiac and pulmonary side effects are distinctly scarce. We believe that if there is any clinical suspicion of coronary artery disease, the diagnostic and prognostic gains from thallium-dipyridamole imaging (with close monitoring) outweigh the small risk attached to the test.

REFERENCES

1 Ladenheim ML, Pollock BH, Rozanski A, Berman DS, Staniloff HM, Forrester JS, et al. Extent and severity of myocardial hypoperfusion as predictors of prognosis in patients with coronary artery disease. J Am Coll Cardiol 1986; 7:464-71

2 Taillefer R, Lette J, Phaneuf DC, Leveille J, Lemire F, Essiambre R. Thallium-201 myocardial imaging during pharmacologic coronary vasodilation: comparison of oral and intravenous dipyridamole. J Am Coll Cardiol 1986; 8:76-83

3 Homma S, Gilliland Y, Guiney TE, Strauss HW, Boucher A. Safety of intravenous dipyridamole for stress testing with thallium imaging. Am J Cardiol 1987; 59:152-54

4 Gerson M, Moore EN, Ellis K. Systemic effects and safety of intravenous dipyridamole in elderly patients with suspected coronary artery disease. Am J Cardiol 1987; 60:1399-1401

5 Homma S, Gilliland Y, Guiney TE, Strauss HW, Boucher A. Safety of intravenous dipyridamole for stress testing with thallium imaging. Am J Cardiol 1987; 59:152-54

6 Lam JYT, Chaitman BR, Glaenzer M, Byers S, Fite J, Shah Y, et al. Safety and diagnostic accuracy of dipyridamole-thallium imaging in the elderly. J Am Coll Cardiol 1988; 11:585-89

7 Gerson M, Moore EN, Ellis K. Systemic effects and safety of intravenous dipyridamole in elderly patients with suspected coronary artery disease. Am J Cardiol 1987; 60:1399-1401

8 Bayliss J, Pearson M, Sutton GC. Ventricular dysrythmias following intravenous dipyridamole during "stress" myocardial imaging. Br J Radiology 1983; 56:686

9 Blumenthal MS, McCauley CS. Cardiac arrest during dipyridamole imaging. Chest 1988; 93:1103-04

10 Heikela A, Haavisto M, Grannas R. Pulmonary uptake of PGE2 is inhibited by dipyridamole in rat isolated lungs. Prostaglandins 1982; 23:147-56

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