Listen in to Dr. Kern and Dr. Lloyd Klein as they discuss this article in a 30-minute Clinical Editor's Corner Live presentation.
Dr. Mike Ragosta from the University of Virginia asked our expert cath lab group an interesting question: “One of my colleagues learned that a patient in whom he was about to perform an elective cath had taken Cialis (phosphodiesterase type 5 [PDE5] inhibitor) the night before and he was concerned about proceeding in case he had to give nitroglycerin (NTG). It has not been part of our screening process or patient instructions to either inquire specifically about use of sildenafil and related drugs, or to hold them for some period of time prior to the catheterization.
While sublingual or long-acting nitrates should be avoided if they have taken Cialis the night before, is there concern that intracoronary (IC) NTG is also a problem? What is the practice regarding this medication in other cath labs? Should we cancel the case?”
Before checking with our experts, I thought this question raised bigger issues as to when we should consider canceling a planned elective cardiac catheterization. While uncommon, we do encounter patients whose pre-cath workup is incomplete. In our lab’s experience, the most common delaying factor is missing recent lab data like the BUN/creatinine, potassium, hemoglobin and platelets or INR (see relative contraindications, Table 1). These critical pieces of information should be known before every cath. However, if you have data from 1 month before the procedure, should we accept that information? Often we do, particularly if the patient has had a completely stable course. But any intervening illness might have changed things and then an update is needed. For example, was there a hospitalization for congestive heart failure or sepsis? Did the patient take too much or too little of a potassium supplement? Was the patient started on oral anticoagulation, but forgot to tell the screening nurse? And lastly, did the patient take sildenafil and not mention it until just before the procedure?
Should You Cancel the Case?
Strictly speaking, any situation that increases procedural risk that cannot be ameliorated or corrected before an elective cath should prompt us to reschedule until that situation is corrected. However, the need to reschedule is balanced against the safety risk. The reality of patients making arrangements to come to the hospital, canceling work, and having someone ready to drive them home makes the patient-centric teams among us consider those relative risk situations. For the patient with missing lab data, we use point-of-care testing or defer the procedure for a couple hours while the blood work is being finished. For the required Covid-19 screening that was missed or is not up to date, we repeat a rapid screen the same day (again, delaying but not canceling the case).
What Should We Do in a Patient Who Took a PDE5 Inhibitor? Let’s See What Our Experts Said.
Mort Kern, Long Beach, California: Mike, I had not given this issue much thought before you asked. The patient’s medications are listed on the pre-procedure form and are reviewed before scheduling. The medications and critical lab values are confirmed with the patient and read aloud to the operating team at the ‘time-out’ immediately before starting the procedure with the patient on the cath table. We don’t routinely screen specifically for sildenafil or other PDE5 inhibitor, beyond asking about all the medications the patient takes.
In some practices, asking about PD5i is a standard policy. All cardiologists know NTG and sildenafil do not mix, and avoid the combination at all costs (if possible) to prevent severe hypotension.
A bigger problem might be that a patient would not tell anyone about using a PDE5 inhibitor. I would guess we’ve had such patients and never known about it. But what do we do if we find out after starting the procedure that the patient was using it? If that’s the case, then we’d have to manage the clinical situation as best we can. If we found out 1 hour before the case, then it’s likely we’d proceed, giving special attention to avoiding using NTG for this patient. While I have no firsthand experience in a patient who took Viagra and then received NTG, I’m sure our some of our colleagues would find great fault if we knew about Viagra use and someone gave him NTG, even accidentally.
Should we cancel (or stop) the diagnostic angiogram because we can’t give NTG to this patient? We probably wouldn’t. However, we might cancel an ad hoc PCI until the drug effect is gone and reschedule it in 2-4 days.
William Fearon, Stanford University, Palo Alto, California: For elective cases, we don’t specifically ask about timing of Cialis or sildenafil use unless it is on the patient’s med list. Acute coronary syndrome (ACS) patients are asked about this in the emergency department (ED) regardless, before getting any NTG. My sense is that we probably use IC NTG in the cath lab in patients on these meds without ever knowing about it and get away with it. Parker et al1 is somewhat reassuring about NTG use in patients who recently received sildenafil.
Lloyd Klein, Sonoma, California: Every outpatient I see scheduled for an elective procedure receives a pre-printed list of information and one of the things it lists is not to use such agents for 24 hours prior to the procedure, and to tell someone on the day of the procedure if a PDE5 inhibitor agent was taken the night or day before. It is standard protocol to ask this question. The ED asks everyone with chest pain as well. That said, I cannot recall a single time when someone said they had used it and I am not exactly sure what we would do if they did. I suppose we would cancel an elective procedure. The fear, of course, is a hypotensive episode with NTG, and this would raise the possibility of a medical as well as a legal risk if it occurred. I am sure Bill is right that we have done so without knowing.
Sam Butman, Cottonwood, Arizona: I think that since intra-arterial NTG used in the cath lab is so short acting, it has not been an issue. It does make one wonder if our occasional need to quickly hydrate a patient who gets hypotensive after we give NTG took sildenafil or the like recently. The hypotension in the cath lab after NTG always seems to correlate with being ‘dry’ (mild hypovolemic) before the procedure.
David J. Cohen, Kansas City, Missouri: I suspect an important factor in mitigating the hemodynamic effect of NTG with sildenafil has to do with the fact that our patients are supine in the cath lab. If we performed the procedure with them upright, we might see a lot more severe hypotensive reaction.
Dawn J. Abbott, Providence, Rhode Island: I want to add that I would not cancel the cath or percutaneous coronary intervention for a patient on a PDE5 inhibitor. We are a pulmonary hypertension center, and we have many patients chronically on these drugs for indications other than erectile dysfunction. We also do procedures on other patients where NTG is relatively contraindicated such as right ventricular infarct, severe aortic stenosis, intramyocardial bridge, etc., so generally we ask and use an alternative vasodilator.
NTG With PDE5 Inhibitors
For a quick review, how does NTG interact with type 5 phosphodiesterase (PDE5) inhibitors (avanafil, sildenafil, tadalafil, vardenafil) to cause hypotension?
PDE5 inhibitors interact with nitrates by decreasing the metabolism of nitric oxide-induced activation of cyclic guanosine monophosphate (cGMP), thereby allowing more cGMP-mediated smooth muscle relaxation or vasodilation (Figures 1-2). When nitrates are given to patients who have taken a PDE5 inhibitor — within the past 24 hours for sildenafil and vardenafil, and up to 36 hours for tadalafil — a significant drop in blood pressure has been observed.2
The Bottom Line
Elective procedures are not emergencies that must be performed just because the patient is scheduled and arrives at the hospital. Patient safety always comes first. It is impossible to justify a complication or adverse reaction in a patient who was electively cathed with a remedial risk of arrhythmia from low potassium or hypoxia from untreated anemia, or acute kidney injury who had a high but untreated creatinine. The same might be said for patients taking a PDE5 inhibitor. Two things are always true: (1) timing is everything (e.g., how long after the drug?) and (2) if you’re really concerned about safety, reschedule.
Disclosures: Dr. Morton Kern reports he is a consultant for Abiomed, Abbott Vascular, Philips Volcano, ACIST Medical, and Opsens Inc.
Dr. Kern can be contacted at email@example.com.
On Twitter @drmortkern
- Parker JD, Bart BA, Webb DJ, et al. Safety of intravenous nitroglycerin after administration of sildenafil citrate to men with coronary artery disease: a double-blind, placebo-controlled, randomized, crossover trial. Crit Care Med. 2007; 35: 1863-1868.
- Webb DJ, Muirhead GJ, Wulff M, et al. Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina. J Am Coll Cardiol. 2000; 36(1): 25-31.