Expert gives advice on perioperative medication management

Much confusion remains about perioperative management of anticoagulants, even though the drugs have been available for several years. And they are only going to become more prevalent, an expert said.

When Steven L. Cohn, MD, FACP, quizzed Internal Medicine 2014 attendees on perioperative management of oral anticoagulants, the audience-response system showed even numbers of doctors choosing 3 different answers.

Although there was only 1 correct response, Dr. Cohn, a professor of medicine and medical director of the UHealth Preoperative Assessment Center at the University of Miami, was not surprised by the results. “Everybody seems to be confused,” he said, despite the fact that the newer oral anticoagulants have been on the market for several years.

Dr Cohn Photo by Kevin Berne
Dr. Cohn. Photo by Kevin Berne

“This is something you need to come to grips with. You're going to see them more and more,” he said. In addition to giving attendees a quick primer on newer oral anticoagulants, Dr. Cohn's session “Perioperative Medicine” reviewed warfarin management (including bridging) and considerations with steroid, cardiac, diabetic, and pulmonary drugs.

“There are 2 schools of thought on how to manage these medications. The first is continue everything, with as minimal disruption as possible to the patient's usual regimen ... The opposite school of thought is ‘Let's not give them anything if they don't need it.’ ... Either one is acceptable. It's up to you,” said Dr. Cohn.

Undoing anticoagulation

In addition to one's philosophy, the bleeding risk of the surgery and the pharmacokinetics of the newer oral anticoagulants should be considered in perioperative management.

Dabigatran, rivaroxaban, and apixaban are all quick-acting drugs. “Within a couple of hours after taking the pill, the patient is anticoagulated,” said Dr. Cohn. “The half-lives are similar, maybe a little bit shorter for rivaroxaban, but there's a difference in their metabolism and renal clearance.”

Of the 3, dabigatran is the most affected by kidney function, and apixaban is the least. Dabigatran, unlike the others, is dialyzable. But “There's really no true reversal agent or antidote. They're studying 4-factor PCC [prothrombin complex concentrate] and working on specific antibodies, but for the most part, you're not going to reverse these drugs quickly,” said Dr. Cohn.

Despite the drugs' differences, their perioperative management is similar. “In general ... you stop them at least one day before for low bleeding-risk [surgeries] and normal renal function, add an extra day for impaired renal function, add an extra day if you want less bleeding effect or no bleeding effect,” said Dr. Cohn.

If bleeding is a particularly big concern, the drugs could be stopped another day earlier, he said. So, for example, in a patient with creatinine clearance below 50 mL/min undergoing a neurosurgical procedure, the oral anticoagulant could be stopped 3 to 4 days before surgery.

Even with that much time off the drug, there's no need for heparin bridging. “I don't believe that anybody should ever be bridged on these drugs,” said Dr. Cohn. “If you're stopping it that extra day or 2 before, it's because you're concerned that drug is still going to be around, so there's no reason to bridge the patient.”


If, on the other hand, a surgical patient is on warfarin and at high risk of a clot, bridging is recommended, according to the American College of Chest Physicians guidelines that Dr. Cohn discussed. High risk includes mechanical valve patients with mitral valves, older aortic valves, or a stroke in the past 6 months; atrial fibrillation patients with a stroke in the past 3 months or a CHADS2 score of 5 or 6; and patients whose venous thromboembolism is either recent (within 3 months) or resulting from severe thrombophilia.

Patients with moderate risk should be bridged or not “on a case-by-case basis,” according to Dr. Cohn and the guidelines. If you do bridge, “low-molecular-weight heparin is preferred over unfractionated heparin for cost-effective reasons—the patient doesn't need to be in the hospital,” he said.

After surgery, you can often put the patient right back on warfarin. “We've backed off on the postop side, as far as bridging with full-dose anticoagulation is concerned in these patients. You start warfarin either the night they have the surgery or the next night. There's no reason to wait several days, as it's going to take at least 3 days or more for a patient to get to a therapeutic level,” said Dr. Cohn. The patient's international normalized ratio (INR) should be checked daily until it's back up to 2.

If, however, a warfarin patient needs urgent surgery, fresh frozen plasma and intravenous vitamin K are options. Alternatively, “you can use either 3- or 4-factor PCC, and in rare cases, only if life-threatening bleeding, would you consider using activated factor 7,” said Dr. Cohn.

Urgent cases, for example, hip fracture patients, may have a little more time for reversing anticoagulation before surgery. “Here what you can do is give a low dose of oral vitamin K, usually 1 to 2 mg. For most patients, at least patients without liver disease, you should be able to drop their INR from the therapeutic range (2 to 2.5) down to less than 1.5 in 24 hours,” he said.

Whether a patient is on warfarin or a novel anticoagulant, whether his surgery urgent or elective, communication is crucial to perioperative medication management. “You need to tell the surgeon and the anesthesiologist: This is what I plan to do, this is how I plan to do it, this is what the time frame will be,” said Dr. Cohn.

Blood pressure and glucose

Anesthesiologists may have strong opinions about some of the other medications that you're debating whether to stop before surgery, for example, angiotensin-converting enzyme (ACE) inhibitors.

“These drugs have been around since the 1980s, and in 25 years when I was in New York, I almost never stopped ACE inhibitors on anybody, never knew of anybody who had refractory hypotension, and the anesthesiologists weren't concerned,” said Dr. Cohn. “But since coming to Miami, the current feeling among anesthesiologists is that they don't want to take a chance and they don't want the patients on them, unless they have heart failure or coronary artery disease, or unless their blood pressure is uncontrolled.”

There isn't any evidence that continuing ACE inhibitors adversely affects rates of heart attack or death, but many clinicians are stopping them, and angiotensin receptor blockers, the day of surgery to be safe, Dr. Cohn said.

Diuretics can go either way as well, with limited evidence showing it makes no difference if you continue or stop the day of surgery. “If the patient's been on it chronically for at least several weeks or more, they've achieved a steady state, and if they take one more dose, they're not going to suddenly dry up and become hypovolemic and hypokalemic,” he said.

Perioperative management of diabetes treatments varies, too. Although many physicians decrease basal insulin on the day of surgery, that may not be necessary. “If the patient is on the appropriate dose of basal insulin, whether they eat or they don't eat, they shouldn't become hypoglycemic the next morning. Only if they're not going to eat for a long time, if they're going to have surgery in the afternoon, if they have severe renal disease or are on dialysis, or if they've had episodes of hypoglycemia would I decrease that insulin dose,” Dr. Cohn said.

Metformin had traditionally been halted 48 hours before surgery, but it should be fine to stop it, as well as other oral diabetes medications, the morning of surgery, advised Dr. Cohn.

Essential meds

Amid all this uncertainty, there are some medications with definite recommendations. “There are certain medications that are considered to be essential and need to always be continued. These include the cardiac medications, pulmonary medications, and steroids,” said Dr. Cohn.

Steroids should not only be continued, but potentially increased, if the patient has suppression of the hypothalamic-pituitary-adrenal axis. This can often be judged by the current dose of prednisone. “If you've been on less than 5 mg per day, if you take alternate-day therapy [of] 10 mg or less, or any dose for less than 3 weeks, there's probably no suppression at all. If you're on 20 mg or more [for] 3 weeks or more, the axis is probably suppressed,” said Dr. Cohn.

Patients in the former category don't need a stress-dose steroid for minor surgery, while those in the latter probably do. The problem is the in-between patients. “You can either give them empiric steroids, or do an ACTH [adrenocorticotropic hormone] stimulation test,” said Dr. Cohn. But there's no definitive evidence on how to act on the test results. “It's all theoretical, which is why I haven't done the test since 1984. I just give empiric steroids,” he said.

Cardiac medications

As for cardiac medications, research shows that beta-blocker therapy should be continued during surgery. “There's evidence of a rebound ischemia and rebound hypertension if it's stopped abruptly,” Dr. Cohn said. Recommendations also call for continuing statins, but there's currently debate about whether to start beta blockers or statins prophylactically before surgery.

Whether and when to stop aspirin is another tricky issue. “This depends on the indication. Why is the patient on the aspirin? What type of surgery are they going for?” said Dr. Cohn. Patients who have had a recent cardiac event, and those undergoing procedures with little bleeding risk, such as cataract surgery, should continue their aspirin.

“In the absence of a recent event or a coronary stent, I would say it can be stopped,” he said. “It probably should be stopped, because the POISE 2 trial showed that there was no benefit in continuing aspirin in terms of reducing perioperative myocardial infarction or death, but there was an increased risk of major bleeding.”

But you might not need to stop aspirin as far in advance as you think, Dr. Cohn said. “The recommendations are to stop it 5 to 7 or even 5 to 10 days before, because aspirin is an irreversible platelet inhibitor, and that's the time frame you would need to replenish your entire pool of platelets,” he said. However, a patient doesn't usually need that many platelets for surgery. Within 3 days, he or she would have at least 50,000 platelets, which should be sufficient for most operations.

“If you're going to stop it, 3 days before is probably OK, especially in somebody that you think is higher risk,” said Dr. Cohn. “If you stop it too far in advance, more than 2 weeks before, there is some evidence of a hypercoagulable state being caused by that withdrawal, so don't do that.”

Patients with drug-eluting stents should be kept on antiplatelet therapy for at least the first 12 months, according to most recommendations. If you have to take them off, continue aspirin, and stop clopidogrel or ticagrelor 5 days before surgery. “Even though clopidogrel is an irreversible platelet inhibitor and ticagrelor is reversible, these are the recommendations,” noted Dr. Cohn. Prasugrel should be stopped 7 days before.

At least a week before surgery is also the recommended time to stop any herbal medications, if you have the chance. “Sometimes you don't even ask, sometimes the patient doesn't volunteer it, sometimes they don't even think about it as a medication,” said Dr. Cohn.

On this issue and generally, perioperative medication management relies on good communication. “You need to give explicit instructions to the patient as to what to take. Ideally it should be written down—a list of their medications, like a medication reconciliation, and then, ‘Take’ [or] ‘Don't take.’”

If the patient is hospitalized, those clear instructions should go to the nurse. “It should be ‘NPO after midnight except for ...’ the medications you want to give. Otherwise, the nurses may say the patient is NPO, and the patient won't get their necessary medications before they go to the OR,” said Dr. Cohn. “And if the surgery is scheduled before the morning medications are due, they should receive them on call to the OR.”