Home Feature The search for a therapy to prevent and treat postoperative ileus

The search for a therapy to prevent and treat postoperative ileus

October 2005

Published in the October 2005 issue of Today’s Hospitalist

An emerging drug class that is generating a buzz among surgeons may also help hospitalists address a common condition among the surgical patients they are co-managing.

That condition, postoperative ileus, may be far from life-threatening, but it affects up to 20 percent of certain types of surgical patients. Research estimates that postoperative ileus lengthens affected patients’ stay by two to three days, costing the U.S. health care system up to a billion dollars a year.

While postoperative ileus is most common after major abdominal surgery, affecting 15 percent to 20 percent of patients, about 10 percent of patients undergoing cardiac or orthopedic procedures develop an ileus.

For years, the condition has been viewed as an unpleasant ” but inevitable “side effect of surgery. Now, however, health care economics have physicians and researchers taking a closer look at the condition “and searching for ways to minimize its impact on patients.

A lack of therapy

The major challenge of treating postoperative ileus is simple: There is no therapy that has been proven to prevent or treat the problem. It’s one reason that surgeons often take a passive view of the condition.

“As surgeons, we learned to deal with postoperative ileus as something that was thought to be normal postoperatively,” explains Conor Delaney, MD, PhD, professor and chief of colorectal surgery at University Hospitals of Cleveland and Case Western Reserve University. “It used to be that you wouldn’t let people eat and drink until their bowels worked, and when they vomited you inserted a nasogastric tube.”

Over the last few years, however, the surgical community has begun to better understand the pathogenesis of postoperative ileus. That has led to some improvements in managing the condition.

In patients undergoing colorectal surgery, postoperative ileus is caused by multiple factors. The condition is thought to be initially triggered by manipulation of the bowel, but it is then exacerbated by the use of opioids, which inhibit gastric motility, delaying the body’s recovery from postoperative ileus. In patients who undergo nonabdominal surgery, by contrast, postoperative ileus is caused almost exclusively by the use of opioids.

Research has shown that patients who have a history of narcotic intolerance or GI problems are particularly prone to postoperative ileus.

Double-edged sword

The pathophysiology of postoperative ileus puts physicians in a bind. Patients need opioids to control significant pain, but the cure may lead to even longer term discomfort. Ileus-like symptoms may be less acute than postoperative pain, but they will keep patients in the hospital for longer periods of time.

“Opiates are a double-edged sword,” Dr. Delaney explains. “You need them to control postoperative pain, but we know that one of their side effects is to slow down gastrointestinal function and recovery.”

An obvious strategy is to minimize the amount of opioids these patients receive, in part by taking them off morphine-based PCAs in one to two days. Most experts talk about switching patients to oral analgesics or NSAIDs as soon as possible, as long as there are no bleeding or renal issues.

But in an era in which physicians are being urged to do more to control patient pain, that strategy gives physicians pause. Amir Jaffer, MD, medical director of the internal medicine preoperative assessment and consultation and treatment (IMPACT) center at the Cleveland Clinic Foundation, says that among the orthopedic surgery patients his service co-manages, one out of 10 typically develops postoperative ileus.

“You have to be careful in terms of balancing the patient’s pain with the ongoing symptoms of postoperative ileus,” Dr. Jaffer says. “People talk about using Toradol intravenously or using other types of COX 1 and COX 2 inhibitors for pain relief. My own view is that postoperative pain is often very severe and that these medications themselves don’t take care of the pain.”

Clinical pathways

Because minimizing opioids in postoperative patients raises questions about pain control, the surgical community has embraced clinical pathways that both manage pain and try to minimize the incidence of postoperative ileus. That approach has become popular in the last year or two.

In addition to minimizing the use of opiates, clinical pathways typically encourage clinicians to get patients up and moving as soon as possible after surgery, encourage feeding patients sooner rather than later, removing nasogastric tubes when they are used, and using other pain medications such as NSAIDs.

“This offers a very integrated package of care where you get people up and moving after surgery,” Dr. Delaney says of clinical pathways. “You don’t use nasogastric tubes, you get them eating and drinking after surgery, and you change them over to oral medications after surgery.”

The key to clinical pathways for postoperative patients is that they combine strategies that by themselves may offer small benefits, but when combined can really make a difference.

“Each strategy may have a small value and lead to a 5 percent or 10 percent improvement,” explains John B. Leslie, MD, professor of anesthesiology at the Mayo Clinic College of Medicine and a consultant in anesthesiology at the Mayo Clinic in Scottsdale, Ariz. “Our best shot is to put them all together so that we have good pain management, good oral management, good nutritional management and good anesthesia management.”

A new drug?

Despite their growing popularity, clinical pathways offer only limited help in preventing and treating postoperative ileus. Dr. Delaney says that about 10 percent of patients who undergo major abdominal surgery, for example, will still experience nausea, vomiting and other ileus-like symptoms.

That’s why there is so much excitement, particularly among colorectal surgeons, about an emerging class of drugs that may help treat postoperative ileus that is currently being reviewed by the FDA. The drug, alvimopan, is a mu-opioid receptor antagonist that has shown promise in several clinical trials.

A study in a 2001 issue of the New England Journal of Medicine found that alvimopan given before and shortly after surgery helped accelerate the return of bowel function in patients and reduced their length of stay by nearly one day. The trials seemed to indicate that alvimopan does not interfere with the effects of opioids and that it is well tolerated by patients.

Subsequent studies, including one that was led by Dr. Delaney, have produced similar results. “What you notice from looking at the reports is that you significantly reduce the number of patients who take 10 or 12 days to recover from surgery,” Dr. Delaney explains. “There appear to be fewer patients with really prolonged ileuses.”

He adds that the drug also seems to reduce the number of patients who need to be readmitted for surgery, as happens when patients return to the hospital a day or two later with nausea and vomiting.

Dr. Delaney is quick to add that not every patient recovers that much more quickly. While some patients see little to no benefit, he explains, others appear to see a large benefit.

Questions remain

While alvimopan has yet to receive FDA approval, it is already generating a buzz among physicians. Dr. Leslie from the Mayo Clinic, who published a review this summer in the Annals of Pharmacotherapy examining trials on the drug, says he has already been receiving calls from orthopedic and gynecologic surgeons asking when they can begin to prescribe the drug.

While he shares their enthusiasm, Dr. Leslie says he hopes his colleagues won’t simply prescribe the drug to all surgical patients if it indeed is approved. “This is not for all colon resections,” he explains, “but it certainly is for patients who the surgeon would list as high risk. It’s certainly good for people who have a previous history of bowel dysfunction.”

He also notes that if it is approved, alvimopan will be only one part of the approach to prevent and treat postoperative ileus. “It does not solve the problem completely,” he says.

Dr. Jaffer from the Cleveland Clinic says that research on alvimopan has piqued his interest, but he adds that he would like to see future studies focus on how the drug can help patients undergoing orthopedic surgery, major spinal reconstructive surgery and urologic surgery.

Based on the research he has seen, Dr. Jaffer also wonders how the drug might help medical patients who are taking opiates and experiencing GI problems. “A lot of our patients who are taking opiates for chronic pain sometimes come in with ileus,” he says. “I wonder if the drug might have a role in our medical patients.”

What constitutes ileus?

While physicians are wondering how a new drug to treat postoperative ileus might affect them, Dr. Leslie has high hopes about how alvimopan may change the way physicians view the condition.

Currently, he explains, many surgeons think it’s normal for colorectal patients to experience some discomfort. Only after symptoms last more than three days, he says, do many physicians consider the condition serious enough to warrant some kind of action. He hopes that if a drug is approved to prevent and treat postoperative ileus, physicians will treat GI symptoms after surgery earlier.

“I remember when we introduced some of the drugs for postoperative nausea and vomiting,” Dr. Leslie says. “People used to say it’s normal for patients to vomit for a while. Today we have a completely different philosophy, which is that we have drugs to prevent all nausea and vomiting, so most patients should get the medication if they’re at risk.”

“This is something that we really don’t understand at this point, and that is how much normal dysfunction is in fact abnormal dysfunction,” Dr. Leslie says. “If we did things correctly, could people actually be eating within one to two days as opposed to four to five days? Currently, if patients don’t eat in four to five days, that’s considered an ileus. Maybe our definition will change to one to two days.”

Edward Doyle is Editor of Today’s Hospitalist.

How one hospital reduced postoperative ileus

If you’re looking for ways to reduce the incidence of postoperative ileus in patients who have undergone nonabdominal surgery, you might consider the example set by North Country Regional Hospital.

The community hospital in Bemidji, Minn., noticed that its rate of postoperative ileus was above average among patients who had undergone five procedures: knee and hip arthroplasty, C-section, hysterectomy and laparoscopic cholecystectomy. When researchers compared the care and outcomes of patients who did and didn’t develop the condition, they found several common themes.

Researchers found that patients who went on to develop postoperative ileus often had a history of GI problems and that they also had low albumins, indicating nutritional problems. They also found that patients who developed an ileus tended to consume far greater amounts of opioids than other patients.

Orthopedic surgical patients who didn’t develop postoperative ileus used about 40 mg of the drug in the first 24 hours after surgery. Patients who went on to develop an ileus, by comparison, used an average of 118 mg of morphine, or almost three times as much of the drug.

Patients taking meperidine after C-sections and hysterectomies showed similar trends, although the timing was different. While patients who did not develop postoperative ileus used 200 mg to 300 mg of the drug in the second 24 hour period after surgery, patients who developed an ileus used 600 mg to 700 mg, or almost twice as much.

The chicken or the egg?

Michelle Bennett, RN, continuous quality improvement coordinator at the hospital and a co-author of a research paper on the topic, recalls that the results raised some important questions. (The paper was published in a 2000 issue of the Journal of Healthcare Quality.)

“Was the ileus already beginning so the patients hurt more and they were using more pain drugs,” she asks, “or did the ileus develop because they were using more drugs? Which came first?”

While it was difficult to answer those questions, the hospital was able to make some changes to address the problem.

For one, nurses began noting on the patient’s medication record exactly how many milligrams of a painkiller patients had used. While nurses had always tracked that information as they changed IV bags, they never entered the information onto patients’ charts.

“We now put that information in the medication administration record, so if the physician came around and wanted to know, he would look at it and see they’re using 120 milligrams. They’ll wonder what is going on,” Ms. Bennett says. “They start to get a clue that this patient can’t tolerate pain very well, and that we might be headed down the path of an ileus.”

Opening up pain conversations

In addition, awareness about the condition led to more detailed conversations about pain.

“Normally when you ask about postoperative pain, you assume that the patient has hip pain because of the new hip,” Ms. Bennett says. “Now we might hear that it wasn’t just the pain in the hip, but pain in the stomach because the patient was feeling bloated. Instead of simply asking ‘How is your pain today?’ the conversation would open up.”

Staff also began to more aggressively wean patients off of opioids. That could mean removing the PCA altogether for patients who could tolerate oral medications. If patients had already started to develop signs of an ileus and could not tolerate an oral medication, nurses might try weaning the patient to a half dose.

The changes, along with the greater awareness that the quality improvement effort created, helped the hospital drive down its rates of postoperative ileus among these patients.

Before the project began, Ms. Bennett notes, 4.8 percent of these patients developed postoperative ileus. Just six months after the project began, the rate of postoperative ileus had dropped to 1.9 percent.

The evidence behind three popular strategies

While physicians have tried many strategies to prevent and treat postoperative ileus “everything from prokinetics to laxatives ” experts say that few treatments have withstood the scrutiny of clinical trials.

“People have a lot of voodoo and will tell you that they’ve been doing something for 20 years,” explains John Leslie, MD, professor of anesthesiology at the Mayo Clinic College of Medicine and a consultant in anesthesiology at the Mayo Clinic in Scottsdale, Ariz. “The problem is that it’s not black and white, and clinicians can’t show you prospective randomized control trials that they really work.”

Here’s a review of what has “and has not “worked in preventing and treating postoperative ileus.

  • Epidurals. One increasingly popular approach is to administer painkillers epidurally both during and after surgery. A body of research has shown that the approach can reduce the amount of opiates that patients receive, as well as the GI side effects of narcotics.

    Dr. Leslie notes that there are concerns that some patients may experience muscle weakness and hypotension after receiving an epidural anesthetic. That’s why he sometimes adds opioids to the mix.

    “We kind of cheat and give them a half and half mixture” of anesthesia and opioids, Dr. Leslie says. “It still reduces the amount of opioids they receive, which improves the return of bowel function.”

    There is another issue with epidural painkillers: Catheters should ideally be removed within about 48 hours to reduce infection. That can limit how long patients receive epidural pain relief after their procedure.

  • Nasogastric tubes. While nasogastric tubes used to be a favorite of physicians to prevent and treat GI problems after surgery, primarily by decompressing the stomach, research has shown that they shouldn’t be used routinely.

    Randomized control trials and meta analyses, in fact, have shown that routinely using nasogastric tubes after surgery can increase complications like fever, atelectasis and aspiration. In addition, they can delay feeding of the patient. That’s why several of the physicians interviewed for this article say they don’t routinely use NG tubes in their postoperative patients.

    “We reserve it for those patients who are very distended and uncomfortable with postoperative ileus,” says Richard Steinbrook, MD, associate professor of anesthesia at Harvard Medical School and director of clinical research in the department of anesthesia at Beth Israel Deaconess Medical Center. “We can decompress the stomach, but nasogastric tubes ought to be used for as brief a time as possible.”

  • Prokinetics. Conor Delaney, MD, PhD, professor and chief of colorectal surgery at University Hospitals of Cleveland and Case Western Reserve University, says that researchers have studied a wide range of prokinetics for postoperative ileus. He notes that many of the studies have been small, and that none produced solid evidence that the drugs reduce the time it takes to recover from postoperative ileus.

    Perhaps the most promising research looked at a drug called cisapride. Despite some promising results, the drug was taken off of the market because of concerns about dysrhythmias. Several other agents, including erythromycin and metoclopramide, remain on the market, but some studies have shown that patients given these drugs actually take longer to recover from postoperative ileus.

    “Physicians have always wanted to have a drug to increase GI motility,” explains Dr. Steinbrook from Beth Israel Deaconess Medical Center, “but studies have not shown that prokinetics work very consistently, and in most patients it’s not clear that they work at all.”