Intrathecal Opioid Dose Research Articles

Intrathecal Opioids for Non-Emergent Cesarian Section In Latin American Women: A Retrospective Cohort Study (Re-Mice Study)

Background: Common use of intrathecal opioids for cesarean sections has been limited due to reported adverse events, despite their significant role in postoperative analgesia. It has been suggested that a dose reduction could potentially reduce adverse effects without affecting efficacy of postoperative analgesia. Objectives: The aim of this study was to identify the most frequently used intrathecal opioid doses by Latin-American women who underwent non-emergent cesarean sections at a reference center and reported adverse events during the first 6, 12, and 24 hours after administration. Methods: We retrospectively analyzed a cohort of women that underwent non-emergent cesarean sections under spinal anesthesia during the period of January 2011 to June 2014. The associations between different doses of intrathecal morphine (≤50; 51-75; 76-100 and 101-150 mcg) with and without intrathecal fentanyl (20-25 mcg) and pruritus, postoperative nausea/vomiting, and respiratory depression probabilities were assessed using a uni-bivariate proportional hazards model and a multivariate logistic model. Results: Out of 1,405 patients treated with any type of intrathecal opioid for cesarean section, 1,314 (93.5%) received intrathecal morphine. We detected a significant association between pruritus probability and intrathecal morphine dose during the first 6 postoperative hours. There was no correlation between postoperative nausea/vomiting occurrence and increasing intrathecal morphine doses. Conclusions: Intrathecal morphine 50 to 150 mcg and intrathecal fentanyl 20 to 25 mcg are effective and safe. During the first 6 postoperative hours, pruritus, but not postoperative nausea/vomiting, shows a significant correlation with intrathecal morphine doses of 75 to 100 mcg.

Lower, Variable Intrathecal Opioid Doses, and the Incidence of Prolonged Fetal Heart Rate Decelerations After Combined Spinal Epidural Analgesia for Labor: A Quality Improvement Analysis.

BackgroundCombined spinal-epidurals with low-dose intrathecal opioids and local anesthetics are commonly used to initiate labor analgesia due to the fast onset of analgesia and good patient satisfaction. Intrathecal fentanyl has been associated with fetal bradycardia, and the rate may be higher at doses of 25 mcg and above. As such, our institution limits intrathecal fentanyl doses to less than 15 mcg for labor. Prompted by a few incidents of prolonged fetal bradycardia at even these low doses, we sought to audit the side effects associated with varying low doses of intrathecal fentanyl.MethodsAfter IRB approval, a retrospective review was performed on 555 labor records from May–December, 2016. All the patients received combined spinal epidurals for labor analgesia. Intrathecal medication consisted of 1 mL of 0.25% bupivacaine, and varying fentanyl doses: 2.5, 5, 10, and 15 mcg. The incidences of prolonged fetal heart rate decelerations, emergent cesarean delivery, magnitude of pain reduction, pruritus requiring treatment, and hypotension were compared.ResultsDemographic variables were equivalent between the groups. There were no differences in the rates of prolonged fetal decelerations (in order of increasing fentanyl dose: 4.4%, 2.3%, 7.6%, 3.0%, p-value = 0.11), emergent cesarean delivery, magnitude of pain reduction, pruritus, or maternal hypotension.ConclusionsIn conclusion, the rates of prolonged fetal heart rate decelerations after combined spinal epidural with intrathecal bupivacaine and fentanyl does not differ for fentanyl doses of 15 mcg and below.

Association Between Oral Pain Medications and Intrathecal Opioid Dose Escalation: A Retrospective Analysis

Patients treated with intrathecal therapy frequently require opioid dose increases to maintain analgesia. The kinetics of intrathecal opioid dose escalation are poorly understood. We hypothesized that antidepressant use, antiepileptic use, and lower baseline oral opioid intake prior to intrathecal pump implantation will be protective against intrathecal opioid dose escalation. Targeted drug delivery medication doses were collected from patients who had an intrathecal pump implanted between 2007 and 2016. From a sample size of 136 patients, the association between antidepressant, antiepileptic, and oral opioid use with intrathecal dose escalation was assessed using statistical models. Individuals using an antiepileptic had an estimated ratio of means (97.5% CI) of opioid consumption of 0.91 (97.5% CI: [0.48, 1.73], p = 0.74) at six months, 0.83 ([0.43, 1.58], p = 0.51) at 12 months, and 0.77 ([0.40, 1.45], p = 0.36) at 24 months. Patients prescribed antidepressants had an estimated ratio of means (97.5% CI) of 1.43 ([0.77, 2.65], p = 0.19) at six months, 1.41 ([0.76, 2.63], p = 0.22) at 12 months, and 1.33 ([0.70, 2.51], p = 0.31) at 24 months. In our secondary analysis of pre-implant oral opioid use, patients treated with high oral opioid doses had a similar pattern of intrathecal dose escalation when compared to patients using low doses of oral opioids. Use of antiepileptics, antidepressants, or low oral opioid doses was not associated with attenuation of intrathecal dose escalation. Intrathecal opioid dose escalation was observed to occur similarly, regardless of baseline oral analgesics concomitantly employed.

Comparative Effectiveness of Targeted Intrathecal Drug Delivery Using a Combination of Bupivacaine with Either Low-Dose Fentanyl or Hydromorphone in Chronic Back Pain Patients with Lumbar Postlaminectomy Syndrome.

Targeted intrathecal drug delivery (TIDD) is an effective interventional pain management modality often used in postlaminectomy patients with refractory chronic low back pain. A combination of intrathecal bupivacaine with an opioid is often used. However, intrathecal catheter tip granulomas have occurred with use of morphine or hydromorphone but generally not with fentanyl. The objective of this study was to compare the efficacy of TIDD using bupivacaine/fentanyl vs bupivacaine/hydromorphone in patients with chronic intractable low back pain postlaminectomy. A retrospective comparative analysis of consecutive patients with lumbar postlaminectomy syndrome who were trialed and later received TIDD with a combination of bupivacaine/hydromorphone or bupivacaine/fentanyl between June 2009 and May 2016 at a single tertiary medical center. We identified a cohort of 58 lumbar postlaminectomy patients receiving a TIDD admixture of either hydromorphone/bupivacaine (30 patients) or low-dose fentanyl/bupivacaine (28 patients) with at least two years of follow-up. The fentanyl group had significantly lower baseline opioid consumption and a lower rate of intrathecal opioid dose escalation. Both groups had similar and significant reductions in pain scores over the two-year follow-up period. No granulomas were observed. TIDD using a low-dose fentanyl admixture with bupivacaine in patients with postlaminectomy syndrome and refractory chronic low back pain results in similar pain relief to TIDD with hydromorphone and bupivacaine. Low-dose intrathecal fentanyl leads to a lower rate of opioid escalation and may be safer than hydromorphone.

Management of oral medication in patients with swallowing difficulties: a joint effort for pharmacists and nurses.

Patients treated with intrathecal therapy frequently require opioid dose increases to maintain analgesia. The kinetics of intrathecal opioid dose escalation are poorly understood. We hypothesized that antidepressant use, antiepileptic use, and lower baseline oral opioid intake prior to intrathecal pump implantation will be protective against intrathecal opioid dose escalation.Targeted drug delivery medication doses were collected from patients who had an intrathecal pump implanted between 2007 and 2016. From a sample size of 136 patients, the association between antidepressant, antiepileptic, and oral opioid use with intrathecal dose escalation was assessed using statistical models.Individuals using an antiepileptic had an estimated ratio of means (97.5% CI) of opioid consumption of 0.91 (97.5% CI: [0.48, 1.73], p = 0.74) at six months, 0.83 ([0.43, 1.58], p = 0.51) at 12 months, and 0.77 ([0.40, 1.45], p = 0.36) at 24 months. Patients prescribed antidepressants had an estimated ratio of means (97.5% CI) of 1.43 ([0.77, 2.65], p = 0.19) at six months, 1.41 ([0.76, 2.63], p = 0.22) at 12 months, and 1.33 ([0.70, 2.51], p = 0.31) at 24 months. In our secondary analysis of pre-implant oral opioid use, patients treated with high oral opioid doses had a similar pattern of intrathecal dose escalation when compared to patients using low doses of oral opioids.Use of antiepileptics, antidepressants, or low oral opioid doses was not associated with attenuation of intrathecal dose escalation. Intrathecal opioid dose escalation was observed to occur similarly, regardless of baseline oral analgesics concomitantly employed.

Long-term Outcomes Using Intrathecal Drug Delivery Systems in Complex Regional Pain Syndrome.

Providing durable long-term pain control for patients with complex regional pain syndrome (CRPS) is challenging. A multidisciplinary approach focused on physical therapy is frequently prescribed, with opioids and invasive procedures reserved for those challenged by functional progression. In this study, we examined the long-term efficacy of intrathecal drug delivery systems (IDDS) in patients with CRPS at our institution. Patients with CRPS implanted with an IDDS between 2000 and 2013 who had four or more years of continuous follow-up were included in the analysis. The outcome variables of interest were pain intensity and oral opioid intake. The primary predictor of interest was dose of intrathecal opioids, with ziconotide, bupivacaine, and clonidine characterized as binary secondary predictors. Of the 1,653 IDDS identified, 62 were implanted primarily for CRPS-related pain. Of these, 26 had four or more years of complete follow-up data. Pain scores did not significantly decrease over time, and we observed no correlation between pain intensity and use of any intrathecal medication. Although oral opioid intake decreased over time, intrathecal opioid dose did not affect oral opioid consumption. Ziconotide was associated with a hastening of the decrease in oral opioid intake, whereas the presence of bupivacaine paradoxically increased oral opioid intake. Our study demonstrates that intrathecal opioid dose was not associated with long-term decreases in oral opioid intake. Additionally, ziconotide was associated with a decrease in oral opioid intake over the four-year follow-up, and bupivacaine was associated with an increase in oral opioid intake. Our study examines the long-term effectiveness of intrathecal medications in managing pain in patients with complex regional pain syndrome. We present a detailed follow-up over four years for 26 patients, tracking oral opiate intake, pain scores, and intrathecal pump settings. Our findings suggest that intrathecal opiates may not be effective in reducing oral opiate intake, ziconotide may hasten a decrease in intake, and bupivacaine may lead to an increase in intake.

Trialing and Maintenance Dosing Using a Low-Dose Intrathecal Opioid Method for Chronic Nonmalignant Pain: A Prospective 36-Month Study.

To evaluate low-dose intrathecal opioid trialing and maintenance with regard to analgesia and psychometric functional capacity. Prospective cohort of subjects offered, trialed and maintained using low-dose opioid therapy via an intrathecal drug delivery system. Analgesia, measured by visual analog scale and the Global Pain Scale, and function, measured by Multidimensional Pain Inventory and Global Pain Scale, are evaluated. Population analysis by age, gender, oral opioid dose, diagnosis, and pain type is reported. Fifty-eight subjects enrolled in the 36-month evaluation period with mean opioid intrathecal opioid dose less than 350 μg per day of morphine equivalent utilized. Primary nociceptive pain type were associated with lower intrathecal opioid doses and improved visual analog scale pain rating and improved pain severity and interference on the Multidimensional Pain Inventory. This study adds to the growing body of literature suggesting that low-dose intrathecal analgesia without oral opioid supplementation can be efficacious. It appears that this approach may achieve analgesia with lower doses in those with primary nociceptive pain type.

Randomised, double-blind controlled trial by dose reduction of implanted intrathecal morphine delivery in chronic non-cancer pain

ObjectiveThis study aimed to investigate the efficacy of intrathecal morphine in the long term by hypothesising that a reduction of the intrathecal opioid dose following long-term administration would increase the...

Intrathecal “Microdosing”: Reality or Artifact?

To the Editor, Hamza and colleagues merit commendation for conducting a prospective study on non-cancer-pain patients receiving intrathecal (IT) therapy ⇓ using the concept of “microdosing”—the practice of weaning patients off systemic opioids prior to implanting an IT drug delivery system (IDDS) using very low opioid dosage. A number of elements, however, remain unresolved and unexplained in relation to hypothesis, design, and execution of the current study. The unproven theory of “microdosing” deserves a close look. The premise of placing an IDDS traditionally centered on providing better analgesia with lesser side effects compared with systemic opioids ⇓. However, patients who require higher IT opioid doses at the trial stage receive significantly higher IT opioid amounts after implant than patients needing lower IT trial opioid doses ⇓ and report worse pain scores ⇓. A small retrospective study suggested that “microdosing” results in sustained pain relief without the need for supplemental oral opioid dosages ⇓. Similar findings were encountered in the current study by Hamza and colleagues ⇓. While these findings are significant, it remains unclear why patients who could tolerate being weaned off systemic opioids would need to have an implanted IDDS infusing low-dose IT morphine. Weaned patients may just be managed off …

A Predictive Model for Intrathecal Opioid Dose Escalation for Chronic Non-Cancer Pain

Background: Tolerance is defined as a phenomenon in which exposure to a drug results in a decrease of an effect or the requirement of a higher dose to maintain an effect. The fear of a patient developing opioid tolerance contributes regularly to the stigmatization and withholding of intrathecal opioid therapy for chronic pain of non-cancer origin. Objectives: The aim of this study was to describe the intrathecal opioid dose escalation throughout the years in chronic non-cancer pain patients. A secondary objective was the development of an intrathecal opioid dose predictive model. Study Design: Retrospective assessment of medical records. Setting: Department of Pain Management, Russells Hall Hospital, Dudley, United Kingdom. Methods: Medical records were reviewed and pump refill notes screened from the date of implant through November 2010 for 31 patients undertaking continuous intrathecal opioid therapy. All the patients included had undertaken a minimum of 6 years of intrathecal therapy when the data were collected. Results: Significant increases in the intrathecal morphine dose were verified between follow-up at one year and all subsequent observations, F (2.075, 62.238) = 13.858, 0 < 0.001, but ceased to be significant from year 3 onwards, indicating stability of the morphine dose, F (3, 90) = 2.516, P = 0.63. A model that accounts for 76% of the variability of morphine doses at year 6 based on year 2 assessment combined with duration of pain prior to initiation of intrathecal therapy was developed: year 6 dose = -0.509 + (1.296 x [year 2 dose]) + (0.061 x [duration of pain]). Limitations: Retrospective study. Conclusion: The opioid dose escalation observed throughout the years was modest and not significant following year 3 of therapy. The model developed has the potential to assist the physician in the identification of a need for alternative treatment strategies. Furthermore, since many of the pump replacements are performed prior to year 6, it can also assist in the informed decision of the benefits and risks of the maintenance of this therapy. Key words: Chronic pain, non-cancer pain, intrathecal opioid therapy, opioid dose escalation, predictive mode

Intentional Intrathecal Opioid Detoxification in 3 Patients: Characterization of the Intrathecal Opioid Withdrawal Syndrome

Intrathecal (IT) drug delivery systems for patients with chronic non-malignant pain are intended to improve pain and quality of life and reduce side effects of systemic use. A subset of patients may have escalating pain, functional decline, and/or intolerable side effects even as IT opioid doses are increased. Discontinuation of IT medications may represent a viable treatment option but strategies to accomplish this are needed. Three patients with intrathecal drug delivery systems (IDDS), inadequate pain control, and declining functionality underwent abrupt IT opioid cessation. This was accomplished through a standardized protocol with symptom-triggered administration of clonidine and buprenorphine, monitored using the clinical opiate withdrawal scale. Symptoms of IT withdrawal were similar in all patients and included diuresis, agitation, hyperalgesia, mild diarrhea, yawning, and taste and smell aversion. Hypertension and tachycardia were effectively controlled by clonidine administration. Classic symptoms of withdrawal, such as piloerection, chills, severe diarrhea, nausea, vomiting, diaphoresis, myoclonus, and mydriasis, were not noted. At 2 to 3 months follow-up, patients reported decreased, but ongoing pain, with improvements in functional capacity and quality of life. This preliminary work demonstrates the safety of abrupt IT opioid cessation utilizing standardized inpatient withdrawal protocols. To our knowledge, these are among the first reported cases of intentional, controlled IT opioid cessation without initiation of an opioid bridge: self-reported pain scores, functional capacity, and quality of life improved. The IT opioid withdrawal syndrome is characterized based upon our observations and a review of the literature.

Combination of Intrathecal Opioids with Bupivacaine Attenuates Opioid Dose Escalation in Chronic Noncancer Pain Patients

The purpose of this study was to examine the effect of intrathecal (IT) coadministration of bupivacaine with opioids during the initial phase of opioid titration and up to 1 year after implantation of an IT drug delivery system (IDDS). The study was designed as a retrospective study. OUTCOMES ANALYZED: The outcomes analyzed for this study were pain relief, oral opioid consumption, IT opioid, and bupivacaine dosage. METHODS AND PATIENT POPULATION: The patient population for this study were consecutively implanted patients over a period of 6 years in a tertiary single center with multiple practitioners. In this retrospective study, 126 consecutive noncancer intractable pain patients were implanted with IDDS and initiated with an IT opioid (O) as a single medication or an IT opioid and bupivacaine (O + B). Pain intensity, amount of oral opioids, dose, rate, and concentration of IT opioids and bupivacaine, and number and type of IT medication used were recorded at preimplant, implant, and at 3, 6, and 12 months postimplant. The intervention used for the study was the IT delivery device implant. Significant reduction in pain intensity was observed in both groups at 12 months postimplant (O group: baseline 7.42 ± 2.1 to 5.85 ± 2.8 [n = 72, P < 0.001]; O + B group 7.35 ± 2 to 5.03 ± 2.4 (n = 54; P < 0.001]). The combination of opioids with bupivacaine from the start of IT infusion treatment resulted in a reduced progression of opioid dose escalation in comparison to patients started with opioids (O group). The rate of increase of IT opioids in the O group at 12 months was 535 ± 180%, whereas in the O + B, the dose increase was significantly lower at 185 ± 85% (P < 0.004). In both groups, there was a statistically significant decrease in oral opioid consumption compared with preimplant doses. Concomitant initial coadministration of IT bupivacaine with opioids blunts the rate of IT opioid dose escalation during the first year after implant of an IDDS. More studies are necessary to thoroughly examine IT opioid dose escalation and the effects of addition of bupivacaine to IT opioids. Blunting IT opioid dose escalation may be a beneficial long-term effect of IT bupivacaine.

Age-dependent Intrathecal Opioid Escalation in Chronic Noncancer Pain Patients

Age and gender may exert important influences on opioid responsiveness and chronic pain. These effects have not been explored in the setting of chronic intrathecal (IT) opioid therapy. The objective of this study was to evaluate the effect of age and sex on IT opioid requirements during the first year after implantation of an intrathecal drug delivery system (IDDS) in chronic noncancer pain patients. Retrospective study. METHODS AND PATIENT POPULATION: In this retrospective study, 135 chronic noncancer pain patients consecutively implanted with IDDSs for opioid therapy had their first year postimplant records examined. Similar pain relief was achieved at 12 months after implant in both age groups. Relative to the dose at implant, younger patients had significantly higher rates of IT opioid dose escalation compared with older patients at 12 months (750 ± 450% in patients ≤50 years old vs 195 ± 120% in patients >50 years old, P < 0.001). Oral opioid consumption was significantly decreased at 12 months in the older patient population (140 ± 89 to 62 ± 35 mg/day at 12 months, P < 0.001, n = 85), while in the younger patient group, there was no change in oral opioid consumption (128 ± 81 mg/day to 105 ± 140 mg/day at 12 months, P = 0.65, n = 50). Gender-based analysis (55% males and 45% females) revealed similar reductions in pain scores during the first year postimplant. Oral opioid consumption was significantly higher in females (126 ± 138 mg) vs males (79 ± 89 mg) at 12 months postimplant; however, IT opioid dose escalation at 12 months postimplant was not statistically different between males and females. IT opioid dose escalation occurs more steeply in the younger (under 50 years old) IDDS patient population without a concomitant significant decrease in oral consumption of opioids. Age-dependent changes may have important clinical implications on the effectiveness of IT opioid therapy in noncancer pain and its potential complications.

Patient Selection and Outcomes Using a LowDose Intrathecal Opioid Trialing Method for Chronic Nonmalignant Pain

Background: Various methods exist for trialing patients for intrathecal drug delivery. Currently no standards exist regarding “best practices” for trialing techniques. Objectives: The specific aim of the current study is to report results of patients trialed using a low-dose intrathecal morphine technique in the treatment of chronic noncancer pain. Setting: academic pain medicine practice Study Design: Retrospective Review Method: Visual analog pain scores (VAS) were obtained at the initial visit, after a 6 week opioid-free interval prior to trial, at intrathecal doses of 25, 50, 100, 200 and 400 µg of intrathecal morphine during the trial, at one month post-implant, and current VAS. Additionally, intrathecal opioid doses at implant and current state are reported. Results: VAS scores at the initial visit and after 6 weeks of opioid cessation were identical. There was a significant improvement in VAS after the trial, which was sustained over the course of therapy. Additionally, the use of the protocol described in this article suggests that the doseresponse relationship following opioid cessation is in the 50-400 µg/d range for intrathecal morphine and that tolerance may be reversed during the 6 week opioid-free period. Limitations: Small trialing study Conclusions: Opioid taper and a 6 week opioid-free period may 1) improve long-term analgesia versus a combination of oral/ intrathecal drug delivery system therapy 2) it may be possible to maintain analgesia at microgram doses and 3) opioid tolerance may be reversible in 6 weeks. Further it appears that a dose response relationship for effective analgesia may be less than 400 µg of intrathecal morphine. Key Words: Intrathecal opioids, intrathecal drug delivery, oral opioid therapy, chronic noncancer pain

Medical Practice Perspective: Identification and Mitigation of Risk Factors for Mortality Associated with Intrathecal Opioids for Non-Cancer Pain

The authors recently determined that early and longer term mortality after initiation or reinitiation of intrathecal opioid therapy is higher than previously appreciated: 0.088% within 3 days, 0.39% at 1 month, and 3.89% at 1 year. These rates were 7.5 (confidence interval, 5.7-9.8), 3.4 (confidence interval, 2.9-3.8), and 2.7 (confidence interval, 2.6-2.8) times higher, respectively, at each interval than expected based on the age- and gender-matched general U.S. population. A substantial portion of this excess mortality is probably therapy related and cannot be entirely accounted for by underlying demographic or patient-related factors, or by device malfunctions. We also analyzed multiple complementary internal, governmental, and insurance databases to quantify mortality and to identify medical practice patterns that appear to be associated with patient mortality risks, and to suggest measures for physicians and health care facilities to consider in order to reduce those risks. Both of those objectives involve judgments, which may be controversial and are subject to practical limitations. Multiple clinical and patient- or therapy-related factors appear to increase the risk for early post-implant mortality. Specific risk mitigation measures associated with each factor include: close attention to the starting intrathecal opioid dose (or restarting dose after therapy interruption); avoidance of outpatient implant or other device procedures that involve less than 24-hour monitoring for respiratory depression; supervision of concomitant opioid, respiratory depressant, or other central nervous system active drug intake early post-implant and chronically in the outpatient setting; and careful programming or dosage calculations and decisions in order to avoid the unintentional administration of high intrathecal opioid drug doses. Mortality after initiation of or device interventions in intrathecal drug delivery patients appears to occur as a result of multiple factors that present possible mitigation opportunities for physicians and health care facilities.

Intrathecal inflammatory masses: is the yearly opioid dose increase an early indicator?

The objective of this study is to investigate the association between intrathecal drug, flow rate, drug concentration, and drug dose with the formation of intrathecal inflammatory masses. A retrospective longitudinal study of 56 consecutive patients receiving long-term intrathecal analgesic administration was undertaken through screening of medical records. Data regarding drug flow rate, dose per day, and concentration of drugs administered were recorded for morphine, diamorphine, bupivicaine, clonidine and baclofen and averages computed. The average follow-up time post-implant was 91 ± 55 months (range: 9-209). Four of the 56 patients were diagnosed with intrathecal granuloma indicating a rate of 7%, the equivalent to 0.009 events per patient year. Twenty-one of the patients had received morphine either alone or combined; 22 had received diamorphine either alone or mixed; and 13 crossed over from morphine to diamorphine or the inverse. None of the patients with granuloma crossed over before diagnosis. A significant correlation was found between opioid dose (r= 0.275, p < 0.05), yearly increase of the opioid dose (r= 0.433, p < 0.05), and granuloma formation. Clonidine appeared to have a protective effect for the non-granuloma patients. No association was found with flow rate (r= 0.056) or opioid concentration (r= 0.214). This is the first detailed study showing an association of diamorphine with granulomas. This study supports the previous finding of intrathecal opioid dose being a risk factor for intrathecal granulomas and clonidine being protective. In addition we have found that the yearly increase in opioid dose is a risk factor for granulomas and could serve as an indicator for closer surveillance.

Use of Intrathecal Bupivacaine in Refractory Chronic Nonmalignant Pain

To demonstrate the efficacy and safety of the addition of bupivacaine in restoring pain control and improving quality of life and activity level in patients with chronic nonmalignant pain refractory to intrathecal opioids. Retrospective study. Outpatient clinics. Seventeen patients with inadequate pain relief while receiving intrathecal opioids alone. Interventions. The intrathecal opioid dose was held constant at 14.19 mg/day following the addition of bupivacaine. The initial bupivacaine dose was 2.08 mg/day and 4.83 mg/day at final follow up. Pain relief, activity, depression, and quality of life were measured by the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), EuroQol 5D (EQ-5D), and Short Form 36 (SF-36), respectively. Reduction in oral medication use, return to employment, and device-related complications were also analyzed. Outcomes were evaluated prior to pump implantation, before the addition of bupivacaine (baseline), and every 6 months thereafter. Seventeen patients were followed for 29.60 +/- 19.01 months. The average pain reduction measured by the VAS was 32.2%. The ODI improved 19.1%; BDI improved 17.9%; EQ-5D improved by 0.56; and the SF-36 showed statistical improvement in six of eight domains. Mean oral/transdermal opioid use reduced from 49.01 mg/day to 23.02 mg/day and oral non-opioid medications reduced from 2.2 classes to 1.0 class after the addition of bupivacaine. Two additional patients returned to work. No neurological sequelae resulted from adding bupivacaine. The addition of intrathecal bupivacaine restores pain control, improves activity level, quality of life, and mental health in this patient group.

Intrathecal Opioid Infusions

Despite the lack of large epidemiologic studies to date, increased reporting of the inflammatory mass phenomenon as a consequence of scientific presentations and “Dear Doctor” letters to physicians, as well as the availability of new preclinical data, motivated the organization of a consensus panel. This panel’s goal was to formulate hypotheses about the etiology of catheter-tip masses and to provide recommendations for clinicians about the detection and treatment of this complication.1,2Together, these papers provide a comprehensive review of the preclinical and clinical data available regarding the incidence, etiology, and clinical features of inflammatory masses associated with intrathecal drug infusion and provide recommendations for screening, detection, diagnosis, treatment, and prevention of these masses. These recommendations emphasize the need for physician awareness, attentive patient follow-up, and maintaining intrathecal opioid dose and concentration as low as possible for as long as possible while still achieving adequate analgesia.It remains that inadequately treated chronic pain is a serious condition that is associated with its own risks and morbidity. In that context, the risk of catheter-tip mass development as a consequence should remain acceptable provided the treatment is effective. The authors thank Drs. McMillan and Aldrete for their interest and their comments. We share Dr. McMillan’s view on the importance of defining the true incidence and risk of inflammatory mass formation. It is clear that the incidence of granuloma formation is underestimated because of the voluntary nature of reporting and the unknown incidence in asymptomatic patients. The authors believe, however, that imaging of all patients on intrathecal therapy for chronic pain is not supported by the current literature. Given the serious adverse impact of this complication and the likely increase in its incidence with long-term intrathecal opioid administration in noncancer pain populations, the authors believe that the same goals can be reached if physicians maintain a low threshold for ordering imaging studies in patients perceived to be at risk. Even subjective or relatively minor symptoms in a patient receiving long-term or high-dose intrathecal opioid therapy may justify an imaging study to rule out the possibility of a catheter-tip mass. Contrast-enhanced magnetic resonance imaging is the imaging modality of choice, although computed tomography–myelography is less costly and also effective in confirming the diagnosis.* The University of Texas M.D. Anderson Cancer Center, Houston, Texas. samuel@neosoft.com

Management of intrathecal catheter-tip inflammatory masses: a consensus statement.

In a companion article, we synthesized current clinical and preclinical data to formulate hypotheses about the etiology of drug administration catheter-tip inflammatory masses. In this article, we communicate our recommendations for the detection, treatment, mitigation, and prevention of such masses. We reviewed published and unpublished case reports and our own experiences to find methods to diagnose and treat catheter-tip inflammatory masses in a manner that minimized adverse neurological sequelae. We also formulated hypotheses about theoretical ways to mitigate, and possibly, prevent the formation of such masses. Human cases have occurred only in patients with chronic pain who received intrathecal opioid drugs, alone or mixed with other drugs, or in patients who received agents that were not labeled for long-term intrathecal use. Most patients had noncancer pain owing to their large representation among the population with implanted pumps. Such patients also had a longer life expectancy and exposure to intrathecal drugs, and they received higher daily doses than patients with cancer pain. Clues to diagnosis included the loss of analgesic drug effects accompanied by new, gradually progressive neurological symptoms and signs. When a mass was diagnosed before it filled the spinal canal or before it caused severe neurological symptoms, open surgery to remove the mass often was not required. Anecdotal reports and the authors' experiences suggest that cessation of drug administration through the affected catheter was followed by shrinkage or disappearance of the mass over a period of 2-5 months. Attentive follow-up and maintenance of an index of suspicion should permit timely diagnosis, minimally invasive treatment, and avoidance of neurological injury from catheter-tip inflammatory masses. Whenever it is feasible, positioning the catheter in the lumbar thecal sac and/or keeping the daily intrathecal opioid dose as low as possible for as long possible may mitigate the seriousness, and perhaps, reduce the incidence of such inflammatory masses.

Long-term Efficacy of Continuous Intrathecal Opioid Treatment for Malignant and Nonmalignant Pain

Continuous intrathecal opioid administration via an implantable pump is an effective method of treatment for chronic pain. This retrospective study examines the long-term effectiveness of continuous intrathecal opioid treatment in patients with malignant and nonmalignant chronic pain syndromes. We reviewed charts from 81 patients with a history of permanent pump implantation between 1989 and 2000 for treatment of chronic pain due to malignant or nonmalignant causes. We conducted follow-up using telephone interviews. Of the 81 patients, 31 had placement of the pump for malignant pain and 50 had placement for nonmalignant pain. Of those with malignant pain, 30 were no longer living at the time of the study. We were unable to locate 21 of those with nonmalignant pain. Of the 30 patients who participated in the study, 24 patients continued to use the pump, and six patients had the pump removed. Follow-up ranged from 2.2 years to 7.3 years, with an average follow-up of 4.5 years. Patient age ranged from 42 years to 84 years with an average age of 64 years. Twenty-two of the 24 patients still using the pump considered it effective at relieving their pain, with an average pain relief of 62.92% ± 16.81%. Eighteen of the 24 patients required oral pain medications for breakthrough pain. All patients had had their intrathecal opioid dose increased since the original time of pump placement. Complications occurred in eight patients, including eight fractured catheters, two coiled catheters, one displaced catheter, three pump malfunctions, two displaced pumps, and two infections, one of which was meningitis. Nine pumps were replaced due to battery depletion. Eighteen of the 24 patients reported no side effects. Those reporting adverse effects named constipation, urinary retention, nausea, anorexia, light-headedness, fatigue, increased hunger, facial flushing, dry mouth, pruritus, and edema as their complaints. This study, along with previous studies of long-term continuous intrathecal opioid administration, demonstrate that it is an effective treatment modality for chronic pain of both malignant and nonmalignant origin.