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This year's crop of perioperative controversies
DVT prophylaxis just got more complicated

Keywords: Hospitalists deal with new DVT guidelines and biomarker recommendations for surgery patients


by Deborah Gesensway



Published in the July 2012 issue of Today's Hospitalist

IN THE PAST YEAR, several studies have muddied the waters surrounding perioperative medicine. A new set of guidelines, for instance, now clouds recommendations for DVT prophylaxis after hip and knee surgery.

At the same time, several longstanding controversies over using biomarkers in perioperative medicine may be settling down. A good example is the debate over whether to check a postoperative troponin level on vascular surgery patients. One of the nation's top experts in perioperative medicine says that while postop troponin levels have not been deemed useful in the past, mounting evidence is
"Recommend 'DVT prophylaxis as per the guidelines.' Let the surgeons decide what they want to use."

–Steven L. Cohn, MD
University of Miami Hospital

starting to make a strong case for the biomarker's utility.

At the Society of Hospital Medicine meeting in San Diego this spring, Steven L. Cohn, MD, director of the University of Miami Hospital's medical consultation service and professor of clinical medicine at the University of Miami Miller School of Medicine, said he "typically" gets a postop troponin level for major vascular surgery patients. "I think screening high-risk patients will be cost-effective," he explained.

And Dr. Cohn noted that other strategies based on biomarkers might become part of upcoming guidelines. Chief among them is checking preoperative B-type natriuretic peptide (BNP) concentrations. Research indicates, he said, that BNP elevations can help hospitalists predict which patients about to undergo vascular surgery have a higher risk for cardiac complications.

The growing body of evidence surrounding BNP levels is getting so strong, said Dr. Cohn, that his group may start using BNP to modify commonly used cardiac risk prediction tools.

DVT prophylaxis
The really big perioperative news, according to Dr. Cohn, concerns DVT prophylaxis for patients undergoing a total hip or knee replacement. In February, the American College of Chest Physicians (ACCP) published new VTE prevention guidelines with important changes that may come as a surprise to hospitalists.

The guidelines now say that any anticoagulant can be used for "a minimum of 10 to 14 days and up to 35 days" following major orthopedic surgery. The recommendation gives a thumbs-up to low-molecular weight heparin (LMWH), fondaparinux, apixaban, dabigatran, rivaroxaban, unfractionated heparin, warfarin and aspirin. The previous guidelines, which were last updated in 2008, had recommended only LMWH, fondaparinux or warfarin for pharmacologic prophylaxis.

While the new guidelines have expanded the pool of anticoagulants, they do so with less authority. The 2008 guidelines' recommendation to use one of three anticoagulants was based on the strongest possible evidence (grade 1a). The current guidelines' recommendation to use any anticoagulant is based on weaker evidence (grade 1b.)

And while the updated guidelines say that LMWH should be used "in preference to the other agents we have recommended as alternatives," the evidence behind that recommendation is even weaker (grades 2b and 2c).

The new guidelines also give a green light to mechanical prophylaxis as an alternative to pharmacologic anticoagulation. But Dr. Cohn pointed out that the only mechanical devices that the guidelines recommend are "portable, battery-powered intermittent pneumatic compression devices capable of recording and reporting proper wear time—18 hours—on a daily basis." Few hospitals have that equipment available, he added.

New guideline goals
"Why did they suddenly change everything we had been doing?" Dr. Cohn asked. In part, it's because orthopedic surgeons criticized the previous guidelines, which focused on all VTE, and the new guideline-writing committee had different goals.

"The focus this time was on symptomatic VTE as opposed to all VTE," he explained. The new guidelines also give more weight to the bleeding risks of the various therapies.

Dr. Cohn's advice to hospitalists? "Recommend 'DVT prophylaxis as per the guidelines,' " he said. "Put that in your note, and then let the surgeons decide what they want to use." He admitted that he personally prefers the drugs recommended in the 2008 guidelines over aspirin.

He also pointed out that if the new guidelines have one overall message, it's that prophylaxis against thromboembolism in general—including for orthopedic surgery patients—should be individualized. Therapy should be based on each patient's risks and benefits, not ordered for every patient as a default.

Dr. Cohn acknowledged that the guidelines have "weakened what we thought of as the bible of antithrombotic therapy." But they are nonetheless the new guidelines, he said, and hospitalists need to "be aware of the recommendations."

Postop troponins
Myocardial infarction (MI) is the most common major perioperative vascular complication. It also comes at a steep cost because postop MIs typically result in higher mortality than those occurring in a non-surgical setting. As a result, Dr. Cohn said, any tool to reduce mortality from postop MIs is most welcome.

Hospitalists may have one such tool at their disposal in the form of troponin elevations. Dr. Cohn said that several recent studies have all concluded that postop troponin elevation predicts not only short-term but long-term major adverse cardiac outcomes as well.

"If two-thirds of postop MIs are asymptomatic," he said, "if most MIs occur in the first 48 hours after surgery, and if most deaths occur within 48 hours of the time when the MI was diagnosed, we don't have much time to intervene."

Complicating matters is the fact that mortality is similar whether patients have symptoms or not. "If you just wait for symptoms of ischemia," he said, "you are going to miss a lot of MIs."

He noted that an upcoming study may provide more information; that study was just published in the June 6, 2012, Journal of the American Medical Association. Researchers working on the international VISION study (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study) found that a peak troponin (fourth generation TnT assay) measurement that was more than or equal to 0.02 ng/mL in the first three days postop was significantly associated with higher 30-day mortality.

The study did not, however, answer several key questions about troponin: How can you distinguish between a true MI and a troponin leak? Which asymptomatic patients should be tested? And what should doctors do with the results?

The bottom line is figuring out whether having this information will change patient management and actually affect outcomes. While these questions remain unanswered, Dr. Cohn said the evidence is tipping toward ordering postop troponins on many vascular surgery patients. "At SUNY Downstate and Kings County Hospital where I practiced for many years before coming to Miami, we had already been doing it for postoperative patients in the ICU," he noted.

In his view, abnormal troponin levels are similar to abnormal results of a stress test—and similar interventions can be used in both situations. "We can monitor vital signs more frequently," Dr. Cohn said, "transfer patients to a monitored setting if they aren't there, and look for and treat potential contributing factors to silent ischemia like hypoxia or anemia."

Hospitalists can also "better manage volume status, start patients on aspirin, and give them beta-blockers, statins and ACE inhibitors," he said. And if patients do have a postop MI, he added, "we could pick it up earlier and possibly send the patient for cardiac catheterization and PCI." Physicians might also recommend outpatient stress testing for patients with troponin leaks. "It's probably better than not knowing anything in the absence of symptoms."

Preop BNP and CRP
Dr. Cohn addressed another longstanding question in perioperative medicine: how to predict which patients about to undergo vascular surgery are more likely to develop a cardiac complication.

This is where the debate over checking preoperative levels of BNP, N-terminal pro b-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) comes up. "This is a hot topic where some evidence may make us change our minds in terms of what we are doing," said Dr. Cohn.

He pointed out that it is well-known that ventricular cardiomyoctes secrete BNP (a prohormone) and NTproBNP (its cleavage product) in response to atrial and ventricular wall stretch, and that preoperative elevations of both are associated with adverse cardiovascular events during non-cardiac vascular surgery. What's unclear is what test to order, when to get it, what levels are abnormal and what to do when levels are elevated.

Several studies and meta-analyses illustrate many of the problems hospitalists have had with the idea of routine BNP testing. Because researchers have looked at different testing methods and timing, as well as different cutoff levels, it's difficult to interpret results.

But a newer, individual patient meta-analysis published in the July 26, 2011, issue of the Journal of the American College of Cardiology indicated that adding BNP levels to the results of another risk stratification calculator (the revised cardiac risk index) improved prediction accuracy.

Dr. Cohn said that the study found that preop BNP testing faces the same problem as other diagnostic tests and stress testing: "The positive predictive value is low. It is about 15%, which means that only one in six patients with a positive result is going to have a complication or die. But the majority of the patients with an abnormal result are still going to do fine."

He noted, however, that BNP may be better in terms of its negative predictive value. "That is above 95%," he said, "which is similar to a negative stress test. That may give you a little more reassurance."

Which to choose?
Studies have also found that an elevated preop CRP correlates with increased postop complications, particularly when you compare pre- and postop levels.

"But it is not as good as the BNP," Dr. Cohn said, "so if you are going to pick one, I would pick the BNP over the CRP." If you add the CRP on top of the BNP, however, "you may get an even better result in terms of predictive ability." What to do with the results and whether management changes will improve outcomes, he added, have not been investigated.

Given all the unanswered questions, Dr. Cohn believes it is premature to recommend getting a routine preop BNP. But the day may be coming when physicians will order the test more frequently.

"Our anesthesiologists in Miami want us to consider using this before vascular surgery," he said. His group is looking into it, Dr. Cohn noted, particularly for patients going for elective vascular surgery if a preoperative exam can take place well in advance of the scheduled surgery.

If BNP elevations can identify high-risk patients at least a week before surgery, hospitalists may be able to lower that risk by starting beta-blockers, statins or ACE inhibitors and by recommending that patients be monitored closely for postop cardiac complications.

Antiplatelet therapy
Here's another longstanding perioperative controversy: how to manage a patient who needs dual antiplatelet therapy because of a drug-eluting stent and urgent surgery. Should you delay surgery to repair a hip fracture, for instance, in order to stop clopidogrel and aspirin to reduce bleeding risk? Or should you continue the drugs to minimize the chance of a postop MI and stent thrombosis?

Dr. Cohn reminded hospitalists that at least one of those questions has largely been resolved in recent years: Early surgery for hip fractures—meaning within 24 to 72 hours of the fracture—can lower the incidence of complications and death.

After receiving a drug-eluting stent, however, a patient needs to be on dual antiplatelet therapy for at least 12 months, according to the most recent guidance from the American Heart Association and American College of Cardiology. (Previous recommendations were for between three to six months after the stent was placed, depending on the type of stent.) The new ACCP guidelines also call for 12 months of dual antiplatelet therapy with low-dose aspirin and a thienopyridine, rather than a single agent alone.

But the ACCP recommendation is weak, Dr. Cohn said, and based on evidence graded as 2c. That means that the risks and benefits are either balanced or uncertain. "We don't know if there is a significant difference in treating for more than a year vs. six to 12 months," he explained.

In addition, he said, nearly a dozen published studies have looked at hip fracture surgery for patients on clopidogrel and aspirin. Taken as a whole, the studies show that stopping clopidogrel temporarily does increase patients' chances of cardiac complications. But those chances seem to peak when patients are off antiplatelet medications for four to eight days. Shortening the time between stopping clopidogrel and surgery results in more bleeds, but Dr. Cohn pointed out that the bleeding incidents reported were usually not life-threatening.

What are the takeaway messages from these studies? The first is to keep patients on dual antiplatelet therapy as much as possible as per the guidelines. The second is that the benefit of going "early to surgery for hip fracture with the effects of the drugs still on board probably overrides the risks." For Dr. Cohn, the risk of a stent thrombosis—which isn't common, but carries a mortality rate up to 40% —outweighs the risk of potential bleeding.

"It seems OK to me to take the patient to surgery within the first couple of days," Dr. Cohn noted. He pointed out, however, that the controversy still isn't over. "Some orthopedic surgeons will say flat out that they will not do it."

Deborah Gesensway is a freelance writer who covers U.S. health care from Toronto.

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