In this chapter we discuss the following classes of medications that are commonly used in the cardiac catheterization laboratory:
- 1.
Sedatives and analgesics
- 2.
Vasodilators
- 3.
Contrast media
- 4.
Anticoagulants
- 5.
Antiplatelet agents
- 6.
Vasopressors and inotropes
- 7.
Antiarrhythmics
3.1
Sedatives and analgesics
3.1.1
Goals
- •
Improve patient comfort.
3.1.2
How?
- •
Midazolam (Versed): 0.5–1 mg intravenous (IV)—can be repeated. Duration of action: 15–80 minutes.
- •
Fentanyl: 25–100 mcg IV—can be repeated. Duration of action: 30–60 minutes. Other opioids, such as morphine can also be used.
3.1.3
What can go wrong?
3.1.3.1
Respiratory failure—hypopnea
Causes:
- •
Excessive sedation may suppress respiratory drive.
Prevention:
- •
Avoid excessive sedation.
- •
Monitor oxygen saturation throughout the procedure.
Treatment:
- •
Stop administering sedation.
- •
Flumazenil (Romazicon) for reversing midazolam: 0.2 mg IV over 15 seconds. If there is no response after 45 seconds, administer 0.2 mg again over 1 minute. Can repeat at 1-minute intervals up to a total of 1 mg.
- •
Naloxone (Narcan) for reversing opioids (Fentanyl, morphine, etc.): 0.1–0.2 mg intravenously; can repeat at 2- to 3-minute intervals until the desired degree of reversal is achieved.
- •
Intubation may be required for severe respiratory depression.
3.1.3.2
Delayed response to oral P2Y12 inhibitors which may lead to thrombotic complications
Causes:
- •
Opioids delay gastric empting and slow-down drug adsorption, such as P2Y12 inhibitor absorption.
Prevention:
- •
Avoid opioids use in STEMI if not deemed necessary.
Treatment:
- •
Use intravenous antiplatelet agents (e.g., cangrelor or GP IIb/IIIa inhibitors).
3.2
Vasodilators
Medications that cause vasodilation can be categorized into those causing mainly large vessel vasodilation (nitroglycerin) and those causing mainly small vessel vasodilation (nicardipine, nitroprusside, adenosine).
3.2.1
Nitroglycerin
3.2.1.1
Goals
- •
Dilate coronary arteries (intracoronary nitroglycerin should be routinely administered before coronary angiography, to prevent coronary spasm and allow accurate interpretation of coronary anatomy).
- •
Treat hypertension.
- •
Treat pulmonary edema.
3.2.1.2
How?
- •
Intracoronary/intragraft: 100–300 mcg.
- •
Intravenous: nitroglycerin drip is usually started at 10 mcg/min and increased by 10 mcg/min at 5-minute intervals until the desired effect is achieved and systolic blood pressure remains above 100 mmHg. Maximum dose is 200 mcg/min.
- •
Sublingual: 0.4 mg.
3.2.1.3
What can go wrong?
3.2.1.3.1
Hypotension
Causes:
- •
Excessive dilatation of peripheral veins, reducing blood return to the heart (decreased preload). Also excessive dilatation of peripheral arteries (decreased afterload).
- •
Coadministration of nitroglycerin and phosphodiesterase type 5 (PDE-5) inhibitors, such as avanafil, sildenafil, vardenafil, and tadalafil.
- •
Hypertrophic obstructive cardiomyopathy (HOCM): nitroglycerin worsens left ventricular outflow obstruction by decreasing both preload and afterload.
Prevention:
- •
Avoid high and multiple doses of nitroglycerin.
- •
Do not administer in patients with hypotension or patients with right ventricular infarction.
- •
Do not administer in patients who have recently received a PDE-5 inhibitor, such as avanafil (Stendra, within prior 24 hours), sildenafil (Viagra, within prior 24 hours), vardenafil (Levitra, within prior 24 hours), and tadalafil (Cialis, within prior 48 hours).
- •
Do not administer to patients with hypertrophic obstructive cardiomyopathy (HOCM).
Treatment:
- •
Do not administer additional doses of nitroglycerin. Nitroglycerin’s half-life ranges from 1.5 to 7.5 minutes.
- •
Administer normal saline.
- •
Waiting (hypotension often resolves after a few minutes).
- •
Administer vasopressors (such as norepinephrine or phenylephrine) in cases of extreme or persistent hypotension. If hypotension persists, also assess for other potential causes, such as bleeding.
3.2.1.3.2
Headache, flushing, dizziness
Headache may occur after nitroglycerin administration due to dilation of intracranial arteries. Dizziness can occur due to the hypotensive effect of nitroglycerin.
3.2.1.3.3
Tachycardia
Reflex tachycardia may result from the hypotensive effect of nitroglycerin.
3.2.2
Nicardipine
3.2.2.1
Goals
- •
Prevent and treat no reflow. Nicardipine is a calcium channel blocker that can be used intracoronary to achieve vasodilation of small arteries. Nicardipine is the preferred agent for treating or preventing no reflow ( Section 25.2.3.2 ), for example, during atherectomy ( Section 19.3 ) and during saphenous vein graft PCI ( Section 18.9.2 ), as it has less hypotensive effect compared with nitroprusside and verapamil and also has shorter duration of action.
3.2.2.2
How?
- •
Intracoronary: 100–300 mcg.
3.2.2.3
What can go wrong?
3.2.2.3.1
Hypotension
This is treated as described in Section 3.2.1.3.1 .
3.2.3
Nitroprusside
3.2.3.1
Goals
- •
Prevent and treat no reflow.
3.2.3.2
How?
- •
Intracoronary: 100–300 mcg.
3.2.3.3
What can go wrong?
3.2.3.3.1
Hypotension
This is treated as described in Section 3.2.1.3.1 .
3.2.4
Verapamil
3.2.4.1
Goals
- •
Prevent radial spasm.
- •
Prevent and treat no reflow.
3.2.4.2
How?
- •
Radial artery: 2–3 mg.
- •
Intracoronary: 1 mg intracoronary over 2 minutes.
3.2.4.3
What can go wrong?
3.2.4.3.1
Hypotension
This is treated as described in Section 3.2.1.3.1 .
3.2.5
Adenosine
3.2.5.1
Goals
- •
Prevent and treat no reflow.
- •
Cause vasodilation during physiologic testing ( Section 12.2.6 ).
3.2.5.2
How?
- •
Intracoronary: RCA: 50–100 mcg.
- •
Intracoronary left main: 100–200 mcg—several thousand mcg could be administered (slowly) in case of no reflow.
- •
Intragraft: 100–200 mcg.
- •
Intravenous: 140 mcg/kg/min, administered through a central vein or a large peripheral vein.
- •
Regadenoson or papaverine (papaverine is not available in the United States) can also be administered for inducing vasodilation. Regadenoson is costly and papaverine may cause ventricular fibrillation.
3.2.5.3
What can go wrong?
3.2.5.3.1
Heart block
Causes:
- •
Adenosine’s effect on atrioventricular node.
- •
This is most likely to occur with injection in the right coronary artery.
Prevention:
- •
Avoid high doses of adenosine in the right coronary artery.
- •
Slow adenosine administration.
- •
Aminophylline administration (250–300 mg intravenously over 10 minutes) may be used to prevent bradycardia during atherectomy of the right coronary artery. Aminophylline is an A1 adenosine receptor antagonist ( Section 19.3 ).
Treatment:
- •
Watchful waiting (adenosine has short half-life).
3.2.5.3.2
Atrial fibrillation
Atrial fibrillation is the most commonly documented adenosine-induced arrhythmia (2.7% after intravenous administration) and is usually well-tolerated except in patients with accessory pathways .
Causes:
- •
Premature ventricular beats occurring during adenosine administration, sometimes during periods of AV block ( Figs. 3.1 and 3.2 ) .
Figure 3.1
Atrial fibrillation occurring after adenosine administration. Adenosine caused ST-segment depression ( arrowheads ). A premature ventricular beat ( arrow ) subsequently triggered atrial fibrillation.
Figure 3.2
Coronary angiography demonstrating an in-stent restenotic lesion of the mid right coronary artery (A). Intracoronary adenosine administration through the right coronary artery (40 mcg) resulted in complete heart block (B), followed by development of atrial fibrillation (C). After stenting the right coronary artery lesion resolved. Sinus rhythm was restored with cardioversion at the end of the procedure.
Reproduced with permission from Mahmood A, Papayannis AC, Brilakis ES. Pro-arrhythmic effects of intracoronary adenosine administration. Hellenic J Cardiol 2011;52:352–3 (Figure 2). Copyright Elsevier.
Prevention:
- •
Same as for heart block above.
Treatment:
- •
DC cardioversion. If cardioversion is not desired, antiarrhythmics, such as amiodarone, and AV nodal blocking agents, such as beta blockers or calcium channel blockers could be used.
3.2.5.3.3
Ventricular fibrillation
Causes:
- •
Torsades des pointes or ventricular fibrillation can be triggered by adenosine administration, usually after a ventricular pause due to the R on T phenomenon ( Fig. 3.3 ), but may also occur without a pause .
Figure 3.3
Coronary angiography demonstrating a bifurcation lesion in the mid circumflex artery ( arrow , A). Administration of intracoronary adenosine to treat no reflow in the circumflex coronary artery resulted in complete heart block, followed by torsades des pointes due to the R on T phenomenon (B). After defibrillation, sinus rhythm was restored (C). Bifurcation stenting using a “culotte” technique provided an excellent final angiographic result with TIMI 3 flow (D).
Reproduced with permission from Mahmood A, Papayannis AC, Brilakis ES. Pro-arrhythmic effects of intracoronary adenosine administration. Hellenic J Cardiol 2011;52:352–3 (Figure 1). Copyright Elsevier.
Prevention:
- •
Same as for heart block above.
Treatment:
- •
Ask patient to cough, as forceful coughing could generate sufficient blood flow to the brain to maintain consciousness until definitive treatment (defibrillation) can be administered.
- •
Defibrillation.
3.3
Contrast media
3.3.1
Goals
- •
Visualize coronary and peripheral arteries under X-ray.
- •
Clear blood from the coronary artery to perform OCT ( Section 13.3.5 ).
3.3.2
How?
- •
Contrast media are injected through the manifold as described in Chapter 6 : Coronary Angiography.
- •
The lowest possible volume of contrast should be administered, as described in Section 28.3.2 .
- •
Isoosmolar contrast media have been associated with lower risk of contrast nephropathy .
3.3.3
What can go wrong?
3.3.3.1
Contrast-induced acute kidney injury (discussed in Section 28.3 )
Contrast-induced acute kidney injury is a potentially serious complication after coronary angiography and PCI. Patients with advanced chronic kidney disease are at the highest risk of developing this complication. Prevention and treatment of contrast-induced acute kidney injury is discussed in Section 28.3 .
3.3.3.2
Allergic reactions
Allergic reaction to contrast agents can occur immediately after administration or be delayed (usually 6–12 hours after contrast administration) and can range in severity from mild (skin rash) to life-threatening (angioedema, anaphylactic shock).
Causes:
- •
IgE-mediated reactions or direct mast cell degranulation.
Prevention:
- •
Use of isoosmolar contrast media as compared with ionic, low-osmolar contrast media (ioxaglate) . However, isoosmolar contrast media have higher risk of delayed skin reactions .
- •
Pretreatment (for patients known to have allergic reactions to contrast administration):
- •
Steroids (usually prednisone 50 mg administered at 13, 7, and 1 hours before the procedure) or 32 mg of methylprednisolone administered 12 and 2 hours prior to the procedure.
- •
Diphenhydramine (Benadryl) 50 mg administered 1 hour prior to the procedure.
- •
Cimetidine 300 mg orally or ranitidine 150 mg administered orally 1 hour prior to the procedure.
- •
- •
If the patient needs emergency coronary angiography and/or PCI, hydrocortisone sodium succinate (Solu-Cortef) 100 mg should be administered intravenously as soon as possible before the procedure.
Treatment:
- •
Diphenhydramine (Benadryl) 25–50 mg intravenously.
- •
Cimetidine 300 mg IV or ranitidine 50 mg IV over 15 minutes.
- •
Steroids, such as hydrocortisone sodium succinate (Solu-Cortef) 100–400 mg administered intravenously over 1 minute.
- •
Epinephrine (for anaphylactic shock) (0.3 mg of 1:10,000 solution intravenously – can repeat to total dose of 1 mg).
- •
Intravenous normal saline.
3.3.3.3
Thyroid dysfunction
Causes:
- •
Contrast media contain high doses of iodine. Iodine administration to patients with underlying thyroid disease may lead to hypersecretion of thyroid hormones, a phenomenon known as the Jod–Basedow effect (usually occurs 2–12 weeks after iodine administration). Iodine administration can also lead to hypothyroidism.
Prevention:
- •
Avoid contrast administration in patients with hyperthyroidism or hypothyroidism.
Treatment:
- •
Referral to endocrinology.
3.4
Anticoagulants
Unfractionated heparin is the most commonly used anticoagulant for PCI . Bivalirudin provides similar outcomes with unfractionated heparin , hence it is currently used infrequently except in patients with heparin-induced thrombocytopenia (HIT) for whom it is the anticoagulant of choice.
3.4.1
Goals
- •
Prevent thrombus formation within the coronary artery or within equipment inserted into the body (sheaths, guide catheters, wires, balloon, stents, etc.).
- •
Reduce the risk of radial artery occlusion (for cases performed via radial access, Section 4.3 , step 9).
3.4.2
How?
3.4.2.1
Unfractionated heparin
3.4.2.1.1
Dose
- a.
Without concomitant glycoprotein IIb/IIIa inhibitor or cangrelor administration: 70–100 units/kg.
- b.
With concomitant glycoprotein IIb/IIIa inhibitor or cangrelor administration: 50–70 units/kg.
- •
Renal failure: no adjustment needed.
- •
Half-life: 1–2 hours—the half-life of unfractionated heparin increases with higher heparin doses (from 30 minutes after an intravenous bolus of 25 U/kg, to 60 minutes after a bolus of 100 U/kg, to 150 minutes after a bolus of 400 U/kg) .
- •
3.4.2.1.2
Monitoring
Monitoring is performed by checking the activated clotting time (ACT) every 20–30 minutes. Goal ACT:
- •
Without concomitant glycoprotein IIb/IIIa inhibitor or cangrelor administration:
- •
Hemochron device: 300–350 seconds (>350 seconds is often recommended for retrograde chronic total occlusion interventions) .
- •
HemoTec device: 250–300 seconds .
- •
- •
With concomitant glycoprotein IIb/IIIa inhibitor or cangrelor administration: 200–250 seconds .
3.4.2.1.3
Reversal
Reversal: heparin can be reversed with protamine: 1–1.5 mg of protamine per 100 units of heparin; not to exceed 50 mg. Protamine should be administered slowly to minimize the risk of hypersensitivity reactions or anaphylaxis. Prior NPH insulin or protamine zinc insulin administration , fish hypersensitivity, vasectomy, severe left ventricular dysfunction, and abnormal preoperative pulmonary hemodynamics increase the risk of such reactions.
Protamine can cause severe systemic hypotension and relative pulmonary hypertension (due to vasoconstriction of the pulmonary vasculature), usually 5–10 minutes after administration. Methylene blue may help recovery from a protamine reaction .
3.4.2.2
Bivalirudin
Bivalirudin is a direct thrombin inhibitor that carries no risk of HIT.
3.4.2.2.1
Dose
- a.
Normal renal function. Bolus: 0.75 mg/kg IV, followed by infusion of 1.75 mg/kg/h IV for up to 4 hours after the procedure .
- b.
Renal failure. Bolus: 0.75 mg/kg IV, followed by infusion. Infusion rate depends on creatinine clearance, as follows:
- •
Moderate (CrCl 30–59 mL/min): 1.75 mg/kg/h
- •
Severe (CrCl <30 mL/min): 1 mg/kg/h
- •
Hemodialysis: 0.25 mg/kg/h
- •
- •
Half-life: 25 minutes.
3.4.2.2.2
Monitoring
Monitoring is performed using the activated clotting time (ACT). Goal ACT:
- •
Without concomitant glycoprotein IIb/IIIa inhibitor or cangrelor administration: 300–350 seconds.
- •
With concomitant glycoprotein IIb/IIIa inhibitor or cangrelor administration: 200–250 seconds.
3.4.2.2.3
Reversal
There is no reversal agent available for bivalidurin. The bivalidurin infusion is discontinued.
3.4.3
Challenges
3.4.3.1
ACT is low after anticoagulant administration
Causes:
- •
Anticoagulant did not actually reach the circulation (e.g., because the intravenous line malfunctioned).
- •
Low anticoagulant dose.
- •
Decreased antithrombin III levels (familial or acquired) may reduce the effect of unfractionated heparin.
Prevention:
- •
Dose anticoagulants appropriately.
- •
Ensure intravenous lines are working properly.
Treatment:
- •
Administer additional anticoagulant doses (potentially through the arterial sheath if there are concerns about the IV line), followed by repeat ACT measurement before proceeding with PCI.
- •
Avoid inserting devices, such as guidewires, balloons or stents in the coronary arteries until after the ACT is in the therapeutic range to avoid coronary thrombotic complications.
3.4.4
What can go wrong?
3.4.4.1
Bleeding
Causes:
- •
Excessive anticoagulation.
- •
Vascular access complication.
- •
Hypertension.
Prevention:
- •
Avoid high doses of anticoagulants.
- •
Monitor anticoagulation level (ACT every 20–30 minutes).
- •
In patients receiving oral anticoagulation (e.g., for atrial fibrillation), oral anticoagulation should ideally be stopped prior to the procedure (as described in Chapter 1 : Planning, Table 1.2 ), unless the procedure is emergent.
Treatment:
- •
Reverse anticoagulation with protamine if unfractionated heparin was administered. Reversal should be performed only after all intracoronary equipment has been removed. There is a risk of stent thrombosis if stents were implanted. Protamine can in itself cause hypersensitivity reactions, as described above.
- •
Further treatment is specific to the site of bleeding.
3.4.4.2
Thrombosis
Causes:
- •
Low dose of heparin or bivalirudin.
- •
Administered anticoagulant did not reach circulation (e.g., due to IV line infiltration).
- •
Defective heparin or bivalirudin batch.
- •
Heparin-induced thrombocytopenia.
- •
Resistance to heparin (e.g., in patients with antithrombin III deficiency).
Prevention:
- •
Assess platelet count prior to the procedure (to ensure that platelet count has not been decreasing, which could be due to HIT).
- •
Administer correct dose of anticoagulants.
- •
Ensure that the IV line is working properly.
- •
Check ACT 5 minutes after anticoagulant administration to ensure that adequate anticoagulation has been achieved before proceeding with PCI.
Treatment:
- •
Thrombus is managed as described in Chapter 20 : Acute Coronary Syndromes—Thrombus, Section 20.9 .
- •
Additional anticoagulant is administered to ensure that the ACT is therapeutic.
3.4.4.3
Heparin-induced thrombocytopenia (HIT)
Heparin administration can cause HIT. There are two types of HIT. Type 1 HIT develops within the first 2 days after heparin administration, and the platelet count normalizes with continued heparin therapy. Type 2 usually develops after 4–10 days from heparin administration and can lead to life-threatening venous and arterial thromboembolism.
Causes:
- •
Type 1: direct effect of heparin on platelet activation.
- •
Type 2: immune-mediated disorder.
Prevention:
- •
Avoid administration of unfractionated heparin, however, as described above, unfractionated heparin is the anticoagulant of choice during PCI.
Treatment:
- •
Type 1: no specific treatment needed.
- •
Type 2: discontinuation of all heparin administration and anticoagulation with non-heparin agents (such as bivalirudin or argatroban).
3.5
Antiplatelet agents
Both oral (aspirin and P2Y 12 inhibitors) and intravenous (glycoprotein IIb/IIIa inhibitors and cangrelor) antiplatelet agents are currently available for use during PCI.
Dual antiplatelet therapy (DAPT) with aspirin and a P2Y 12 inhibitor is the current standard of care for PCI, except in patients on oral anticoagulants (warfarin or direct oral anticoagulants) in whom aspirin is usually discontinued after the procedure and they only receive clopidogrel in addition to the oral anticoagulant.
3.5.1
Dual antiplatelet therapy
3.5.1.1
Goals
- •
Prevent stent thrombosis.
- •
Prevent future acute coronary syndromes.
3.5.1.2
How?
3.5.1.2.1
Medication type
Medication type: all patients (except for those receiving warfarin or direct oral anticoagulants or those who have allergic reactions) should receive aspirin (although recent studies, such as the TWILIGHT study, have suggested that aspirin can often be discontinued after 3 months with the patients only continuing ticagrelor). Clopidogrel is the P2Y 12 inhibitor of choice for stable CAD patients and prasugrel or ticagrelor for ACS patients, unless contraindicated.
3.5.1.2.2
Dose
- •
Aspirin : 325 mg loading dose, then 81–100 mg daily. Aspirin is commonly stopped in patients who receive oral anticoagulants after an initial periprocedural or longer treatment period (from 1–4 weeks to 6 months after PCI). Patients continue treatment with oral anticoagulant and a P2Y 12 inhibitor.
- •
Clopidogrel : 600 mg load, ideally given at least 6 hours prior to PCI for stable patients, followed by 75 mg daily thereafter.
- •
Ticagrelor : 180 mg load, followed by 90 mg bid . Ticagrelor is contraindicated in patients with prior intracranial hemorrhage and should be avoided in patients receiving strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin), strong CYP3A inducers (e.g., rifampin, phenytoin, carbamazepine, and phenobarbital), and simvastatin and lovastatin at doses greater than 40 mg daily.
- •
Prasugrel : 60 mg loading dose, followed by 10 mg daily maintenance dose (5 mg daily dose for patients with body weight <60 kg or patients aged >75 years). Prasugrel is contraindicated in patients with prior transient ischemic attack or stroke .
3.5.1.2.3
Pretreatment
Stable CAD patients : not done before diagnostic angiography, but should be given if the patients have planned PCI.
Non-ST-segment elevation ACS : no .
STEMI : yes, either before or at the latest at the time of PCI , with either ticagrelor 180 mg or prasugrel 60 mg .
3.5.1.2.4
Switching between oral P2Y12 inhibitors
