Thursday, October 18, 2012

Long-Term Intrathecal Opioids Aid Chronic Pain

OpioidsThere has been considerable debate over benefits of the long-term administration of opioid analgesics for chronic pain, with some saying opioids are unhelpful or even harmful due to the development of tolerance, side effects, or paradoxically increased pain. New evidence suggests that intrathecal opioid administration, at low dose, not only ameliorates chronic, severe pain consistently over several years, but increases functionality, without side effects, and dramatically minimizes the need for oral opioids.

Maged Hamza, MD — at Virginia Commonwealth University Spine Center, Richmond — and colleagues conducted a prospective cohort study to examine long-term outcomes with the use of low-dose intrathecal opioids for the treatment of intractable, severe, chronic noncancer pain [Hamza et al. 2012]. Intrathecal drug delivery uses a small programmable pump, sometimes called a “pain pump,” that is surgically implanted and administers medication directly into the spinal cord.

A total of 61 consecutive patients (60% females, 40% males; mean age 59 years and mean duration of symptoms prior to implant of 6 years) underwent an initial test trial of intrathecal opioids to assess patient response to the therapy. As a part of the test and preimplantation protocol, all patients were gradually weaned from oral opioids they had been taking and later allowed to resume those medications as necessary after pump implantation.

Three of the patients did not respond as expected to intrathecal opioids during the test phase and 58 patients went on to be implanted with a pump. The total followup period was 3 years, with assessment intervals at 6, 12, 18, 24, and 36 months. The Brief Pain Inventory (BPI) was used for assessments at baseline prior to implant and during followup points throughout the study. Outcome measures included self-reported pain scores (worst and average), functional improvement, intrathecal opioid dose, and oral opioid consumption.

ITopioidsWriting in the October edition of Pain Medicine, the researchers report observing statistically significant reductions in both worst and average pain from baseline (8.91 and 7.47, respectively) consistently throughout the duration of the study (4.02 and 3.41, respectively, at 36 months; P = 0.012 and P < 0.001, respectively). See the figure with 95% CIs.

Similarly consistent patterns over time of statistically significant improvements in physical function and behavioral factors (mood, sleep, relationships) were observed. Furthermore, all subjects showed a large and significant reduction in oral opioid consumption.

The dose of intrathecal opioids remained low and virtually unchanged during 36 months of followup: for example, 1.4 mg morphine/day at 6 months and 1.48 mg/day at 36 months. At the same time, oral opioid consumption decreased notably on average from about 127 mg of morphine equivalent dose (MED)/day at baseline to roughly only 4.0 mg MED/day at 3 months — a 123 mg/day decrease in MED — and remained at that low level throughout the study.

The authors conclude that low-dose intrathecally administered opioids can provide sustained, significant improvements in pain and function during long-term therapy for severe chronic noncancer pain, while also markedly decreasing the need for oral opioid analgesics.

COMMENTARY: This was an observational trial in a relatively small group of select patients who had responded favorably to a test trial of intrathecal morphine, and there was no control group for comparison purposes. So, further research would be helpful in confirming the noteworthy results of this study.

All patients had previously failed multiple medical management approaches for their chronic severe pain. Approximately 88% of patients had been diagnosed with either failed back surgery syndrome or low back pain, and the remainder had CRPS (complex regional pain syndrome), abdominal pain, or pelvic pain.

Relatively few studies have examined the benefits and risks of long-term opioid therapy for chronic pain, and this lack of evidence has been cited as suggesting that such treatment may be unhelpful and/or inappropriate [eg, see discussions of the PROP petition here and here]. This current study by Hamza et al. [2012] presents a strategy that achieves long-term (at least 3 years) benefits for severe cases of intractable pain while greatly minimizing the need for oral opioid analgesia and potential adverse effects.

The authors note that, overall, about 73% of patients self-reported more than 50% improvement in pain and nearly 38% achieved more than 75% improvement. At the same time, the authors reported that adverse effects of therapy were mild, limited, medically manageable; including surgical site infection, peripheral edema, pruritus, or fluid pockets (seroma) in 2 to 3 patients each. The absence of usual adverse effects often attributable to opioid therapy — eg, tolerance (requiring increasing doses), constipation, nausea, etc. — was possibly due to the low intrathecal dosing and equally low need for oral opioids, the authors believe.

Perhaps of some consequence, after pump implantation all patients were encouraged to participate in physical therapy and at-home exercise activities, and were offered access to a support group that met quarterly. These interventions may have contributed to enhanced physical and behavioral functionality scores over time, as well as highly favorable global impressions of pain and functional improvement.

The researchers found their approach to be uniformly successful, and there were no differences in this regard between the type of pain, prior duration of pain symptoms, the dose of intrathecal opioid, and outcome results. Yet, this protocol may not be appropriate for all patients with intractable chronic pain since, even in this relatively small study, roughly 5% (3/61) of patients were found to be unresponsive (trial failure) during the test phase prior to pump implantation.

REFERENCE: Hamza M, Doleys D, Wells M, et al. Prospective Study of 3-Year Follow-Up of Low-Dose Intrathecal Opioids in the Management of Chronic Nonmalignant Pain. Pain Medicine. 2012;13:1304–1313 [abstract].

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