RENEW OR SUBSCRIBE TO PPM
Subscription is FREE for qualified healthcare professionals in the US.
12 Articles in Volume 7, Issue #8
A Clinical Guide to Weaning Off Intrathecal Opioids
Avoiding the Pitfalls of Opioid Reversal with Naloxone
Central Role of Dopamine in Fibromyalgia
CES in the Treatment of Insomnia: A Review and Meta-analysis
Combined Phrenic Nerve Palsy and Cervical Facet Joint Pain
Dextrose Prolotherapy for Unresolved Neck Pain
Low Level Laser Therapy - Part 1
Mistakes Made by Chronic Pain Patients
Near-infrared Therapeutic Laser and Pain Relief
Patulous Eustachian Tube: Part 2
The “Promise” of Pain Medicine: Profession, Oaths, and the Probity of Practice
Three Dimensional Imaging of the Foot

A Clinical Guide to Weaning Off Intrathecal Opioids

This clinical guide was developed to help clinicians wean patients from intrathecal opioid therapy

Some patients find IT opioid therapy not effective despite a successful trial. I wrote a column on the failure of IT trials to predict success in the March 2007 issue of this journal (Vol 7: Issue 2). Fortunately, physicians have options to opioid IT therapy but need to know how to rotate from opioid IT therapy to an alternative IT therapy without causing the patient discomfort or side effects. This article by Rosenblum et al provides the readers an example of how this rotation can occur with minimal side effects and adequate analgesia throughout the rotation. Other physicians may have an equally effective method, but for these authors, the process described in this article seems to be safe and effective for them. It may provide the reader an option as well.

Weaning a patient with chronic pain from intrathecal opioids may be considered in a number of circumstances. During the course of intrathecal opioid therapy, patients sometimes experience intolerable adverse events or develop tolerance to the opioid.1 Some patients may have an inadequate response.

Weaning of patients with chronic pain from intrathecal opioid therapy can seem a challenging prospect. Many clinicians mistakenly adhere strictly to the belief that any decreases in intrathecal opioid doses should be replaced with equianalgesic doses of systemic opioids. Various equianalgesic oral to intrathecal dosing ratios have been suggested, ranging from 12-to-1 to 300-to-1.2,3 Such ratios are used for conversion from systemic dosing to intrathecal dosing, and one cannot assume that the ratios would be equivalent for conversion from intrathecal to systemic opioid dosing.3 Additionally, the ratios may be more suitably applied to acute pain patients. These equianalgesic doses are typically inappropriate for weaning from chronic intrathecal opioid therapy. Such patients can be weaned without strict adherence to equianalgesic conversion ratios.

In addition to the dosing concerns that clinicians may have about weaning patients from intrathecal opioids, other issues exist regarding the weaning process. Patients may have a component of psychological dependence and may be anxious at the prospect of weaning. Also, some patients may experience opioid withdrawal effects during the weaning process. Signs and symptoms of opioid withdrawal include lacrimation, rhinorrhea, yawning, insomnia, restlessness, mydriasis, nausea, vomiting, diarrhea, piloerection, abdominal cramps, anxiety, agitation, muscle twitching, diaphoresis, a feeling of “heart pounding,” flu-like feelings, hypertonia, and increased pain.4,5 Hypertension and hyperthermia may also occur in rare cases.4 Withdrawal symptoms vary widely in type and severity among patients and may be affected by the type of opioid, dose, duration of use, frequency of dosing, degree of dependence, rate of weaning, and psychological factors (e.g., depression, distress, mental state at the time of withdrawal).5-9 Opioid withdrawal is generally not life threatening, but it can be very unpleasant for patients.4 This article will focus on the weaning off intrathecal opioids, but clinicians should also be aware of issues that they may encounter when discontinuing other intrathecal medications. Clonidine and baclofen may be associated with dangerous, sometimes life-threatening withdrawal syndromes upon abrupt discontinuation,10-16 whereas other intrathecal drugs (e.g., ziconotide, local anesthetics) can be discontinued abruptly without issue.17

Guidelines for Weaning

Risk Assessment. Before the intrathecal opioid weaning process begins, patients should undergo a risk assessment to help determine if weaning is appropriate and how aggressive the weaning schedule should be. In cases of serious infection, immediate removal of the intrathecal pump without weaning off intrathecal opioids may be warranted. In less serious cases—or when pump explantation is elective—ultra-rapid weaning may be appropriate. This ultra-rapid weaning can be accomplished in a few days but should occur only in an inpatient setting.

In an outpatient setting, rapid, aggressive weaning can be completed in approximately 16 days, whereas slower, less aggressive weaning can take up to two months (but may be accelerated as tolerated). Patients with significant cardiac disease or poorly controlled hypertension may require a longer and more conservative weaning schedule. Results from animal studies have indicated that cardiovascular changes—such as increased heart rate and/or blood pressure—may be associated with morphine withdrawal.18-20Case reports21,22 exist that describe cardiovascular events such as “broken heart” syndrome and myocardial ischemia associated with opioid withdrawal (opioid and benzodiazepine withdrawal in the latter case). A history of sensitivity to opioid withdrawal may also warrant a less aggressive weaning schedule. Additionally, less aggressive weaning may be advisable for patients with a minimal social support structure; patients who live alone may have more difficulty contacting their clinic or physician if problems arise during the weaning process. Finally, less aggressive weaning may be appropriate for patients who have a history of requiring high doses of opioids and/or who have had frequent dose increases. There is evidence to suggest that patients receiving higher opioid doses may be more prone to experience withdrawal syndrome than are patients receiving lower doses.23 High doses and frequent dose increases may also reflect a patient’s psychological dependence on opioids, and the patient’s anxiety and fears should be addressed before beginning the weaning process. In such patients, inadequate pain relief may serve as a motivator for change, and the patient should be a partner in the decision to begin weaning from intrathecal opioids. If none of the conditions discussed above are present, an aggressive weaning schedule may be considered

Intrathecal Opioid Weaning Protocol. Figure 1 provides a brief summary of the suggested intrathecal opioid weaning protocol. The patient’s intrathecal opioid dose should be decreased by an amount that is in the range of 10 percent to 25 percent of the current dose. Decrements of 10 percent are appropriate for slow weaning, whereas 25-percent decrements can be used for aggressive weaning.

The initial dose reduction should be followed by a four- to seven-day stabilization period. During this period, patients should be assessed for symptoms of opioid withdrawal. Scales, such as the Clinical Opiate Withdrawal Scale, can be used to document and assess the severity of signs and symptoms of withdrawal.24 The frequency and severity of withdrawal symptoms can be related to the rate of opioid weaning6; therefore, assessments of withdrawal symptoms are useful in determining the magnitude of further intrathecal opioid dose decreases.

After the stabilization period, the intrathecal opioid dose should again be decreased in the range of 10 percent to 25 percent of the patient’s initial intrathecal opioid dose (based on the frequency and severity of withdrawal symptoms), followed by another four- to seven-day stabilization period. Dose decreases (10 percent to 25 percent of the patient’s initial intrathecal opioid dose), followed by four- to seven-day stabilization periods, should continue as tolerated. The magnitude of the dose decrement (as a percentage of the patient’s initial intrathecal opioid dose) should decrease as the patient nears the end of the weaning process. For example, if a patient has undergone three dose reductions (each being 25 percent of the original dose) and is receiving a dose that is 25 percent of his or her original dose, the remaining decreases should be performed in smaller decrements (e.g., three decreases, each being one-third of the patient’s current intrathecal opioid dose, or approximately 8 percent to 10 percent of the original dose).

Dose decreases should be individualized for each patient. Patients should be assessed for symptoms of withdrawal at the end of each stabilization period to guide the next dose decrease. Patients may be less anxious if they know they will be evaluated by their physician before a further decrease in dose.

Initial dose decreases can be achieved through reductions in the flow rate of the intrathecal pump. However, as the weaning process progresses, the pump may be operating at or near the slowest possible flow rate, making a desired dose reduction impossible to achieve through a decrease in flow rate. In such a case, a more dilute solution is required, but the drug concentration in the catheter and the pump tubing will remain at the previous (higher) concentration. Therefore, overdosing of the patient could occur if the pump flow rate is increased. Bridge bolusing should be used to deliver the drug remaining in the tubing and catheter at the appropriate flow rate to ensure proper dosing. The volume of the catheter and pump tubing should be calculated to determine the bolus amount, and the pump should be programmed for the proper bolus duration. Refer to guidelines from the manufacturer of the patient’s particular intrathecal pump for specific bridge bolusing instructions.

Figure 1. Summary of intrathecal opioid weaning protocol.

The final step in conversion to intrathecal therapy with a nonopioid drug is to fill the intrathecal pump reservoir with normal saline. This action allows for an interim period during which catheter patency is maintained until treatment with the nonopioid drug begins.

Facilitation of the Weaning Process

A number of steps can be taken to facilitate the weaning process and make it as smooth as possible. An information sheet given to patients before weaning begins may be helpful. This sheet should explain the weaning process and include information about intrathecal drugs and about symptoms that patients may experience. Since patients who are more anxious about the withdrawal process appear to report more intense discomfort during weaning,7 information about weaning may help dispel patients’ fears.

The use of a short-acting systemic opioid analgesic (e.g., oxycodone, hydrocodone) at appropriate dosing intervals may assist in the weaning process and minimize withdrawal symptoms. The prescription should be small and limited (e.g., seven-day expiration date), and patients should be allowed to judiciously regulate their own use of this drug. Assessment of patients for symptoms of opioid withdrawal (e.g., with the Clinical Opiate Withdrawal Scale) is helpful in determining the appropriate dose. The dosing for this short-acting opioid should not be equianalgesic to the decrease in the intrathecal opioid dose. Equianalgesic oral to intrathecal dosing ratios as high as 300-to-1 have been proposed2; however, as Sylvester et al3 pointed out, such ratios are for conversion from systemic dosing to intrathecal delivery, and one should not assume that ratios would be the same for conversion from intrathecal to systemic opioid dosing. Practitioners should be sensitive to the possibility that oral medication doses may vary during the weaning process. Additionally, communication with the patient’s pharmacy and insurance carrier can minimize the potential for mishaps with oral medication use during the weaning period.

Providing prescriptions to patients for additional nonopioid medications to treat withdrawal symptoms may help allay anxieties about the weaning process. Clonidine (oral or transdermal, 0.1 mg as needed)—a central a2-adrenergic agonist that has long been used in the treatment of opioid withdrawal symptoms25-28—is one medication option. Use of oral (rather than transdermal) clonidine may facilitate rapid titration to an effective dose. Another option is oral hydroxyzine (25-50 mg, three times daily as needed), a piperazine derivative antihistamine that has been used in the treatment of opioid withdrawal symptoms for more than 20 years. However, oral hydroxyzine is still considered a fairly novel treatment.29

“The overall goal is not equianalgesic conversion, but rather the prevention or minimization of opioid withdrawal symptoms. A short-acting opioid can be made available to the patient via a small, limited prescription in order to minimize the symptoms of opioid withdrawal.”

Discussion

Successful weaning of patients from intrathecal opioids may not be as difficult as it is commonly perceived to be. A recent study of intrathecal ziconotide included a three-week period during which patients were weaned from all intrathecal medications.30 There was no specific weaning protocol for this study, so the weaning schedule was at the discretion of each investigator. One hundred ninety-eight patients required weaning from intrathecal morphine and/or other intrathecal drugs, and the weaning process was successful in 93 percent of these patients. Only 14 patients were discontinued from the study during the weaning period.

Thompson et al31 described three cases in which patients receiving intrathecal opioid therapy were converted to intrathecal ziconotide monotherapy. The intrathecal opioid weaning process lasted 4 weeks, with weekly dose decreases in decrements equal to 25 percent of the original opioid dose. Conversion to ziconotide monotherapy was considered successful in two of the patients. The third patient experienced emotional distress and was not responsive to educational and psychological interventions or to adjunctive anxiety medications. The authors suggested that screening for psychiatric disorders and susceptibility to anxiety or stress should be considered for patients who may undergo weaning off intrathecal opioids and conversion to monotherapy with a nonopioid intrathecal drug such as ziconotide.

Several situations may warrant the weaning of a patient from intrathecal opioids. Regardless of the reason for weaning, a schedule can be tailored to meet the needs of the patient while minimizing the symptoms of withdrawal. The aggressiveness of the weaning schedule will vary between patients and will depend on the medical and psychological condition of the patient before weaning, as well as the patient’s reaction to dose decreases.

A common misconception regarding intrathecal opioid weaning is that any reduction in the dose of intrathecal opioids must be replaced with equianalgesic doses of systemic opioids. This task would be quite daunting, since equianalgesic oral to intrathecal dosing ratios suggested in the literature vary widely.2,3 The overall goal is not equianalgesic conversion, but rather the prevention or minimization of opioid withdrawal symptoms. A short-acting opioid can be made available to the patient via a small, limited prescription in order to minimize the symptoms of opioid withdrawal. Also, keeping the patient well informed regarding the weaning process and providing a prescription for additional nonopioid medications (e.g., clonidine, hydroxyzine) to treat withdrawal symptoms may help allay the patient’s anxieties about weaning and make the process easier.

Summary

Not all pain is responsive to treatment with opioids. If a patient’s pain is found to be refractory to intrathecal opioid therapy, opioid rotation and/or combination therapy, weaning off intrathecal opioids, and pursuit of other treatment options (e.g., nonopioid intrathecal drugs such as ziconotide and clonidine) should be considered. With the guidelines provided here, weaning off intrathecal opioids while also minimizing patient anxiety and avoiding the symptoms of withdrawal can be successfully accomplished. n

Disclosure and Acknowledgments

Financial support for this article was provided by Elan Pharmaceuticals, Inc. The authors would like to thank MedLogix Communications, LLC, for contributions to the development of this article.

Last updated on: December 20, 2011
close X
SHOW MAIN MENU
SHOW SUB MENU