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5 Tips for Managing Opioid-Tolerant Patients
How to handle the special post-op analgesia needs of this growing patient population.
Yasmine Iqbal
Publish Date: October 10, 2007   |  Tags:   Anesthesia

The number of people taking opioids such as codeine, oxycodone and hydrocodone to manage chronic pain has skyrocketed in the past few years. Although these medications can make daily life bearable for people with cancer, traumatic injuries or other painful diseases and disorders, the tolerance that they develop as a result of taking them can make it much more difficult to get adequate pain relief after surgery. In this article, we'll discuss how to handle the special post-op analgesia needs of opioid-tolerant patients.

Understand tolerance
"Opioid tolerance is a natural physiologic consequence of taking these medications," says Christopher Wu, MD, associate professor of anesthesiology at the Johns Hopkins University Medical School in Baltimore. As the body adjusts to the medication, higher dosages are needed to get the desired effect. Almost everyone who takes opioids regularly will develop tolerance, adds Jeffrey Swenson, MD, associate professor of anesthesiology at the University of Utah School of Medicine in Salt Lake City. "While we can't say for sure that every patient who takes opioids is tolerant, I've never seen one who isn't," he notes.

Although tolerance isn't well understood, experts now realize that it doesn't take a lot of medication to cause it - more than four tablets of oxycodone/ acetaminophen daily or acetaminophen 300 mg/codeine 30 mg for several weeks can be enough, says Dr. Wu. It doesn't take very long to occur, either. "Some experts believe that tolerance can start building within minutes when large doses of short-acting drugs are used," says Dr. Swenson.

It's critical to identify patients who may be opioid-tolerant and recognize that they'll probably need greater and more frequent post-op doses of opioid and non-opioid agents than patients who've never taken these medications. They may also need to taper medication more gradually. "The amount of medication that these patients require is sometimes so off the scale that doctors are afraid of prescribing the correct amount because it is out of the usual standard of care," says Dr. Swenson. Withholding dosages or not administering enough will leave patients in distress and may exacerbate post-op pain. It's also important to remember that these patients are usually less affected by some effects of opioids, such as itching, nausea and vomiting, but aren't immune to dangerous effects such as respiratory depression.

Determining Baseline Opioid Requirements

Scenario: A 46-year-old man has just had ankle hardware removed on an outpatient basis. He was taking eight tablets of a combination medication containing 5mg of oxycodone and 325mg of acetaminophen every day for two months before surgery. He is tolerating clear liquids. What would be this patient's baseline opioid requirement, and how should it be replaced?

Answer: Eight tablets are equivalent to 40 mg/d of oxycodone. To replace the baseline dosage, a sustained-release formulation of oxycodone could be given at a dosage of 20mg PO bid.

- Courtesy Christopher Wu, MD

Develop a pre-op plan
Opioid-tolerant patients may be particularly concerned and even fearful about the post-op period, especially if they've experienced uncontrolled post-surgical pain before, says Dr. Swenson. So it's important to discuss pain-control options with them and develop a plan well in advance. Points to remember:

  • One clinician, usually the surgeon or anesthesiologist, should oversee the pain plan, but everyone who cares for the patient, particularly the PACU nurses, should be aware of the patient's special analgesia needs.
  • Determine exactly how much medication patients are taking before surgery, as they will need at least that amount plus additional dosages to combat their chronic and acute pain (see "Determining Baseline Opioid Requirements"). Determining the baseline dosage might require some investigation, because some patients may not know the exact amount they're taking offhand, and they may be taking more or less than prescribed.
  • Confirm any contraindications to non-opioid agents such as acetaminophen or NSAIDs. In most cases, they can provide valuable supplemental pain relief.
  • Because patients may not be able to take medications orally immediately after surgery, make sure you can administer them transdermally, rectally or intramuscularly.
  • As long as they comply with food- and liquid-intake guidelines, patients taking sustained-release opioids should continue their medications on the day of surgery to prevent a sudden drop in serum opioid level and a corresponding lapse in post-op analgesia.
  • Finally, for patients who are suspected to have very high levels of tolerance, it may be advisable to perform even minor surgical procedures on an inpatient basis.

Researchers Develop Guidelines for Opioid-Tolerant Patients

Anesthesiologists at the University of Utah School of Medicine, led by associate professor Jeffrey Swenson, MD, and assistant professor Jennifer Davis, MD, have developed a method to determine the level of opioid needed to provide pain control in opioid-tolerant patients. The researchers studied 20 opioid-tolerant patients undergoing inpatient back surgery. They gave each patient an infusion of fentanyl until the patient showed signs of respiratory depression. Once respiratory depression occurred, the patient underwent general anesthesia. The researchers then used pharmacokinetic simulation software to determine the effect site concentration of fentanyl that caused the respiratory depression to occur. They knew that for most opioid-na've patients, the minimum effective fentanyl concentration needed to provide post-op pain relief is about 30 percent of the concentration that causes respiratory depression.

The researchers found that the concentration of fentanyl needed to cause respiratory depression in opioid-tolerant patients (a mean of 20.74 ng/ml) was significantly higher than that reported in opioid-na've patients (2 ng/ml). Immediately post-op, they let the opioid-tolerant patients titrate their own doses of post-op fentanyl using an IV PCA (initial PCA settings provided doses that would achieve 30 percent of those levels causing respiratory depression). They found that the amount needed for adequate pain relief averaged 7.07 ng/ml, a significantly higher dose than that required in opioid-na've patients. Furthermore, the fentanyl dose required for pain relief among the individual patients varied from 2.1 ng/ml to 22.3 ng/ml - in other words, some patients required 10 times as much fentanyl for pain relief.

University of Utah anesthesiologists now regularly use this protocol to safely and accurately predict the level of post-op opioid their patients will need. The study won an award at the International Anesthesia Research Society earlier this year and will appear in a future issue of Anesthesia and Analgesia.

- Yasmine Iqbal

Consider regional anesthesia
Regional anesthetic techniques, such as epidural catheter placement, might be particularly useful for opioid-tolerant patients because they cut down on the need for post-op opioids and may provide better long-term pain relief, notes Dr. Wu. Epidural anesthesia might have other benefits, as well, such as an earlier return of GI function. (See "6 Tips for Better Blocks" on page 35.)

Be aggressive in the PACU
Ideally, pre-op and intraoperative measures will create a steady-state level of opioids in the patient that will prevent pain altogether, or at least keep it at an acceptable level. However, if patients wake up in pain despite all precautions, it's important to treat them aggressively. Some tips:

  • Pain assessment. Make sure you can assess pain quickly and accurately. The Joint Commission on Accreditation of Healthcare Organizations (www.jcaho.org), the American Pain Society (www.ampainsoc.org) and the American Society of Anesthesiologists (www.asahq.org) have all developed guidelines and tools for assessing pain. If you have the patient use a pain scale to rate pain intensity, make sure the one you choose is developmentally, physically, emotionally and cognitively appropriate.
  • Pain pumps. Consider using pain pumps that let patients safely self-medicate (when possible, discuss this option with the patient and incorporate it into the pain plan beforehand).
  • Adjuvant agents. As long as they aren't contraindicated, use adjuvant agents such as acetaminophen, NSAIDs and COX-2 inhibitors to supplement post-op pain control. These agents don't provide adequate analgesia on their own, but they can reduce the need for high dosages of any one medication. It's most effective to administer these agents on a round-the-clock rather than a PRN basis, says Dr. Wu.

Monitor patients closely
Don't release patients until they and their caregivers know exactly how to combat pain at home, experts say. Dr. Wu's patients, for example, usually take a sustained-release preparation of opioid or transdermal fentanyl to provide basal analgesia, as well as a short-acting PRN dose, such as morphine immediate-release, oxycodone or hydromorphone, for additional or breakthrough pain. Dr. Swenson notes that it may be advisable to make more than one follow-up call to ensure that patients are getting adequate pain relief at home and are following post-op instructions.

Tolerance vs. addiction
Finally, don't confuse tolerance with addiction, which is a psychological craving for opioids. Some healthcare providers are reluctant to administer high dosages for fear of creating or fostering an addiction. But most experts agree that if patients have no history of addiction, the chances of developing one in the healthcare setting is very low.

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