Evaluation of Continuous Intraspinal Narcotic Analgesia for Chronic Pain From Benign Causes

Despite long-standing experience with implantable opioid analgesic drug delivery systems,¹ there are surprisingly few data regarding the effect of this invasive therapy on psychosocial outcomes in patients with intractable, nonmalignant pain syndromes.² The primary factors that have been alleged to influence the response to intrathecal (IT) opioid therapy include depression, malaise, and physical and psychological addiction.³

Because chronic pain is a subjective and multidimensional experience resulting from the interaction of physiological, emotional, and cognitive factors,⁴ there is a high probability that psychological factors will significantly influence the patient's response to the pain experience. Interestingly, the presence of a normal psychological profile (i.e., the Minnesota Multiphasic Personality Inventory) does not necessarily correlate with better clinical outcomes with respect to pain control after implantation of an IT morphine pump.

The peer-reviewed literature regarding spinal cord stimulation suggests that psychological testing of patients with chronic pain before this invasive procedure improves the clinical outcome. However, there are minimal data regarding the psychosocial effects of IT opioid delivery systems in chronic pain populations.⁵ Therefore, we designed a prospective study to evaluate the impact of IT morphine on emotional factors affecting pain perception and psychosocial functionality. Our secondary objectives were to assess changes in morphine consumption during the 24-mo study period and the patient's ability to resume normal activities (e.g., return to work, and ability to live independently).

METHODS

This prospective, IRB-approved study initially included 10 men and 32 women (average age of 69 ± 13 yr) who were experiencing severe chronic pain (pain score ≥7) involving the back and lower extremities for more than 2 yr (average of 5.5 ± 3.3 yr) (Table 1). The patients were all evaluated by multiple pain specialists and none of the patients was deemed to be a candidate for a surgical procedure to alleviate the pain symptoms. After obtaining written, informed consent, a pain therapist interviewed each patient to collect his/her clinical history and use of analgesic medications.

Table 1:

Etiology and Duration of Chronic Pain Symptoms in the 30 Patients Receiving an Implantable Morphine Infusion Pump

All of the study patients were taking opioid and nonopioid analgesic medications at the time they enrolled in the study. Before enrolling in this study, 17 of the patients were receiving oral opioid analgesics, specifically, morphine (5 patients), 480–600 mg/day; oxycodone (5 patients), 240–300 mg/day; transdermal therapeutic system (TTS) fentanyl (4 patients), 150–200 μg/h; or buprenorphine (3 patients) 105–140 μg/h. The remaining 25 patients had experienced opioid-related side effects with low doses of opioids (e.g., oral morphine [<120 mg/day], oral oxycodone [60 mg/day], fentanyl TTS [50 μg/h], and buprenorphine TTS [35 μg/h]). These patients were not receiving any opioid analgesic therapy when they enrolled in this study. All patients were receiving maximally tolerated dosages of anticonvulsants (e.g., gabapentin, pregabalin) and nonsteroidal antiinflammatory drugs. Despite evaluations by multiple specialists and use of maximally tolerated doses of conventional multimodal analgesic drugs, these 42 patients continued to experience unacceptable levels of pain.

The criteria used to determine candidates for implantation of the IT infusion system were as follows: 1) 50% pain relief during a prestudy trial period with a percutaneous epidural catheter system for infusing morphine, 2) absence of intolerable opioid-related side effects (e.g., pruritus, nausea, and vomiting) with the trial of spinal opioid therapy, and 3) absence of personality disorders or preexisting psychiatric conditions. A sequential group of 42 patients took part in a pretest with a continuous epidural infusion (morphine 0.5–1.0 mg/day) using an elastomeric pump that delivered the opioid infusion at a rate of 0.5 mL/h for 3 wk. Thirty of the initial 42 patients enrolled qualified for the implantation of the morphine infusion pump. Of the 12 patients who failed to receive a permanent pump, 8 failed to satisfy all of the above criteria and 4 decided against having an implantable pump for personal reasons.

In this prospective study, the 30 patients who qualified for the permanent pump were evaluated using the McGill Pain Questionnaire (MPQ) before ("baseline") and at 3-, 12-, and 24-mo intervals after implantation of the morphine infusion pump. The same clinical psychologist performed all the MPQ evaluations.⁶ The MPQ is a qualitative multidimensional evaluation instrument consisting of 78 adjectives.⁷ In the Italian version, 20 subclasses of descriptors are grouped to give the measurement of 3 primary pain components named sensorial, affective, and evaluative and of 2 mixed sensorial and affective/evaluative components. Patients were instructed to identify only those adjectives that described their pain in each of these subclasses. The score ranges from a minimum of 0 to a maximum of 5. For example, in the subclass 16, there are 5 descriptors: 1 = annoying, whereas 5 = intolerable. The number chosen is then divided by the total number of specific pain (component) descriptors. Therefore, if the descriptor is scored a 5 and the adjective has a score of 5, the score for the subclass would be 1.⁸ The reliability and validity of the MPQ measurement has been demonstrated in the peer-reviewed literature.⁹

Each patient was asked a few specific questions (Table 2) to assess their level of physical activity and ability to live independently at baseline, 3-, 12-, and 24-mo intervals after implantation. The baseline functional status for the 30 patients receiving the implantable pumps is described in Table 3.

Table 2:

Questionnaire Used to Assess Patient Functionality

Table 3:

Baseline Functional Status for the 30 Patients Receiving the Implantable Morphine Infusion Pump and Status at the End of the 24-mo Study Period

All of the pumps were implanted by the same physician (GD) using local anesthesia with sedation provided by a propofol infusion. With the patient in the right lateral decubitus position, an IT catheter was introduced at L3-4 and advanced under fluoroscopy to T9-10. The catheter was sutured to the prevertebral band and subcutaneously tunneled up to the left iliac hollow just below the iliac crest, where a subcutaneous pocket was created for the pump (ISOMED 20 mL, Medtronic, Minneapolis, MN). The initial morphine dosages varied between 0.09 and 0.75 mg/day at the end of the epidural pretest period.^10,11 At follow-up visits, the morphine infusion rate was varied to maintain a pain relief score at least 50% lower than the initial value when the patient entered the study (baseline). During the first month, pain scores were measured at weekly intervals using a visual analog scale (VAS), with 0 = no pain to 100 = worst pain imaginable. Subsequently, pain measurements and dosage adjustments were made at each refill visit. The follow-up MPQ qualitative evaluations were performed at 3-, 12-, and 24-mo intervals after implantation of the IT morphine pump.

Statistical Analysis

Data are expressed as mean standard deviation, percentages (%), and numbers (n). The statistical analysis was performed using a standard SPSS software package (Chicago, IL). For continuous variables, 1-way analysis of variance and repeated measures of analysis of variance were used to evaluate changes over time. Student's t-test was used to analyze the parametric data, and discrete (categorical) variables were analyzed using the χ² test, with a P value <0.05 considered statistically significant. A Bonferroni correction was performed on outcome variables with multiple comparisons over time.

RESULTS

The serial MPQ evaluations performed on the 30 patients enrolled in this study revealed a progressive improvement in all the qualitative components of their pain assessment (Fig. 1).

Figure 1.:

McGill component improvement rate. For every component, the percentage represents the improvement between each follow-up (3, 6, and 12 mo) and the baseline evaluation. Significant changes between the various components at follow-up evaluations compared with baseline values are indicated with an asterisk (P < 0.05).

Of the 30 patients studied, 29 reported good to excellent satisfaction with the IT opioid therapy. In addition, the coefficients of the various components of pain were significantly reduced over time (Fig. 2). Although the VAS pain scores were significantly lower at the 3-mo assessment period (Fig. 3), the affective component of pain was significantly changed only when compared with the baseline value despite the fact that the morphine infusion rate increased significantly throughout the study period (Fig. 4). The evaluative component of the pain response displayed the greatest improvement and was statistically improved at each testing interval compared with baseline (P < 0.005). There were no clinically significant complications or opioid-related side effects requiring discontinuation of the IT morphine infusion.

Figure 2.:

Mean value for all components measured at each time interval. Every component tended to decrease at each time interval. The values at follow-up visit compared with baseline changed significantly (P < 0.05). Significant changes are indicated with an asterisk.

Figure 3.:

Mean visual analog scale pain scores (and standard errors of the means) and percentage improvement in mean pain scores over time. There was a significant difference from baseline values (P < 0.05). Significant changes are indicated with an asterisk.

Figure 4.:

Average morphine infusion at initial (baseline), 3-, 12-, and 24-mo follow-up evaluation periods. The values at follow-up visit compared with baseline changed significantly (P < 0.05). Significant changes are indicated with an asterisk.

An unexpected secondary benefit of the IT opioid therapy was that 26 of the 30 patients were able to improve their activities of daily living, and 12 of these patients actually were able to return to full-time employment. Among 17 retired patients, 14 improved their functional status and 8 of them no longer required live-in assistance.

DISCUSSION

The most important outcome measures for patients with intractable chronic pain are symptom reduction and improvement in level of activity. The ultimate goal of this IT morphine therapy was to improve the patients' quality of life and allow them to resume their normal activities of daily living. This study demonstrated that the use of a continuous IT morphine infusion reduced intractable chronic pain by modifying its quality and perception. In addition, an unexpected benefit was that 26 of the study patients were able to resume their normal activities of daily living, and 12 of the 13 patients with jobs were able to return to full-time employment. In addition, 14 of the 17 retired patients improved their functional status and 8 of them no longer required live-in assistance. A deficiency of this preliminary study was the failure to quantify the functional improvement in the patients' level of activity from their pretreatment baseline state. In future studies, specific functional testing should be performed before and after initiation of the IT infusion therapy.

Despite the time-related increase in the average morphine infusion rate, the efficacy of the therapy was maintained during the 24-mo study period as evidenced by the maintenance of a >50% decrease in the VAS pain (versus baseline) score throughout the study period. Although the progressive increase in the IT morphine infusion rate was likely related, in part, to development of tolerance to the central effects of the opioid analgesic, other factors that may have contributed to the increase in the morphine infusion dosage during the study period were the fact that some of these patients were tapered off their oral or TTS opioid analgesic medications and most of the patients were able to increase their level of physical activity and functionality during the 24-mo study period.

The observed improvement in the evaluative and affective components of the MPQ suggests that this invasive pain therapy had a positive impact on the lives of this group of patients who had failed to achieve acceptable pain relief with an aggressive multimodal analgesic regimen. In fact, every one of the study patients had been receiving maximally tolerated doses of oral and/or TTS opioids without achieving a satisfactory reduction in their level of chronic pain. The fact that more than 80% of these patients were able to resume their normal activities of daily living (and 12 were able to return to full-time employment) was an unexpected positive outcome in this chronic pain population. The 5 patients who continued to require assisted living care despite significant improvement in their pain symptoms had other debilitating medical conditions (e.g., parkinsonism, paraplegia, and neurologic deficits due to a previous cerebrovascular accident).

In contrast to other studies in the pain literature in which patients with "nociceptive" pain experienced a dramatic reduction of the affective dimension of their pain in response to an IT morphine infusion,¹² we observed only small changes in the affective component of their chronic pain. In fact, the value recorded at the 24-mo follow-up visit was not significantly different from that recorded at the 3-mo follow-up assessment visit. We would speculate that this finding may be related to the fact that only a few of our patients were experiencing pure nociceptive pain. Other authors¹³ have reported that long-term administration of an IT morphine infusion improved the sensorial component more than the affective component of pain in patients with neuropathic pain symptoms.

In this study, the evaluative component of pain displayed the greatest improvement over the 24-mo evaluation period. These data further suggested that, during the course of IT morphine therapy, the impact of the pain on the patients' functionality changed. For example, before treatment with IT morphine, patients were more focused on their pain symptoms. However, after receiving IT morphine, patients were more attentive to other life-related issues. Although long-term use of opioid analgesics in patients with chronic, nonmalignant pain remains controversial,¹⁴ it would seem that the IT morphine infusion can be beneficial in a subset of patients with diverse chronic pain syndromes.

The functional improvements we observed were most marked in the chronic pain patients who were relatively less disabled at the time they entered the study. From a societal point of view, patients who either returned to work or no longer required assistance with activities of daily living would seem to experience the greatest benefit from this therapy. Even in a resource-limited health care environment, IT morphine therapy can be cost-beneficial if it is used in appropriately selected patients with intractable chronic pain. However, expensive pain therapies such as IT morphine infusions should be directed to those patient populations who are likely to experience the greatest improvement. Therefore, future studies should be designed to identify patients who would be most likely to achieve a significant benefit from this invasive therapy.

In conclusion, these preliminary data suggest that, in patients with persistent severe pain despite receiving maximally tolerated doses of multimodal analgesic therapies, use of an IT morphine infusion via an implantable pump should be considered if the patient responds favorably (>50% decrease in their baseline VAS pain score without experiencing opioid-related side effects) to a trial of the therapy using a percutaneous epidural catheter system.

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© 2009 International Anesthesia Research Society

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Source: https://journals.lww.com/anesthesia-analgesia/Fulltext/2009/12000/Improvement_in_Psychosocial_Outcomes_in_Chronic.39.aspx

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