Functional Improvement with Continuous Intrathecal Morphine Infusion in Chronic Non-Cancer Pain

Special Article – Chronic Pain Rehabilitation

Phys Med Rehabil Int. 2018; 5(2): 1141.

Functional Improvement with Continuous Intrathecal Morphine Infusion in Chronic Non-Cancer Pain

Genni Duse* and Giulia Demo

1Pain Therapy Unit, Department of Emergency, S. Antonio Hospital, Padua, Italy

*Corresponding author: Genni Duse, Pain Therapy Unit, Department of Emergency, S. Antonio Hospital,Padua, Italy

Received: February 19, 2018; Accepted: March 16, 2018; Published: March 23, 2018


Aim of the Study: To investigate the long-term (24 months FU) results of continuous intrathecal morphine infusion on functional abilities and quality of life in patients suffering from chronic low back and leg non-cancer pain.

Materials and Methods: 44 patients, at with chronic non-cancer pain, unresponsive to multimodal analgesic therapy, were selected after a three week trial period with epidural infusion of morphine*. The sample size as been defined by ethics committee because of a prospectical and observational study. After informed consent and positive trial period, patients underwent to implantation of an intrathecal morphine infusion programmable pump. Pain intensity (VAS: 0-100), functional abilities (Oswestry Disability Index, ODI), and quality of life (Short Form 36 Health Survey, SF-36) were assessed at baseline, 12 and 24 months after the implantation. Adverse side effects and complications were also recorded in order to investigate the safety of the therapy.

Results: 43 patients reached the 12 months follow up (FU) and 39 of them reached the 24 months FU. Back and leg pain significantly decreased from baseline to 12 months FU visits (p<0.001). Performance Functional Status, evaluated with ODI, significantly improved from baseline to each FU visit (p<0.001). For what concerns Quality of Life analysed with SF-36 questionnaire, at 12 months a significant improvement was obtained in Physical Component and Mental Component Scores (p<0.001), we had significant scores also at 24 months (p<0.001).

Conclusions: continuous intrathecal morphine infusion, using implantable programmable pumps, is helpful for pain control, and shows functional activity, patients’ health status and quality of life could also be improved.

Keywords: Intrathecal morphine; Chronic pain; Spinal cord; Pain intensity; Functional status; Quality of life


Chronic back and/or lower limbs pain are common in patients suffering from failed back surgery syndrome (FBSS), osteoarthritis and spinal stenosis. This kind of patients is generally difficult to treat, because the severe nociceptive and neuropathic pain presented is often untreatable with conventional therapies [1]. Since these syndromes affect the vertebral column, pain usually increases with the movements and is associated with severe disability, seriously compromising functional abilities and quality of life [2]. For this reasons a multidisciplinary approach is usually required that include, in addition to drugs, physical and psychological therapies.

Furthermore, pharmacological treatment may lead to tolerance, addiction or side effects due to prolonged and high doses administration [3,4].

Intrathecal drug delivery (IDD) by means of an implanted programmable pump may be an effective option for chronic pain, allowing a dramatic reduction of the administered doses and side effects [3-7]. However, in literature, only few studies consider the outcomes in terms of functional abilities and quality of life in patients treated with IDD. Probably this is due to different selection criteria and to different methodological approaches as well as poor use of standardized questionnaires, such as Oswestry Disability Index and SF-36 for functional improvement and quality of life assessment [8].

In our study 44 patients with chronic non-cancer pain, unresponsive to multimodal analgesic therapy, were selected after a three weeks trial period of epidural infusion with morphine. In our previous study we evaluated the impact of the emotional and psychosocial aspects affecting pain perception in 30 patients suffered chronic pain. We observed that the use of a continuous IT morphine infusion reduced intractable chronic pain modifying its perception in terms of intensity and quality. In addition, we found that 87% of patients were able to restore, totally or partially, their daily activities and 92% of patients employed were able to return to full-time employment [9].

However, we didn’t quantify patients’ functional improvement from the pre-treatment baseline state to the follow up. The aim of this data collection is to evaluate functional status and quality of life in patients with FBSS treated with intrathecal morphine in the normal clinical practice.

Material and Methods

This study was performed by means of a clinical data collection approved by S. Antonio Hospital Institutional Review Board and conforms to the principles outlined in the Declaration of Helsinki. Outpatients from the Pain Unit at S. Antonio Hospital (Padua, Italy) were assessed according to the common clinical practice by multiple pain specialists. All patients had severe predominant nociceptive non-cancer chronic back and/or legs pain, not successfully treated by means of conventional therapies.

All patients had a long history of pain and tried different kinds of systemic drugs (analgesics and opioids rotation) with poor results in pain management or with intolerable side effects due to the prolonged and high doses undertaken. Nobody was eligible to further surgical procedures useful to reduce pain.

In our centre the IT morphine infusion is commonly used when conventional therapies failed.

Patients, after informed consent, are trialed a three weeks percutaneous epidural morphine infusion by an external infusion pump. During the trial period all analgesic systemic drugs were removed in order to detect the real effect of the therapy. Pain intensity was assessed before and after the test with Visual Analogic Scale (VAS, 0-100), where 0 means no pain and 100 worst pain imaginable. The starting morphine dose is 1mg/die and it is gradually increased to 5mg/die. Patients were considered responder to the treatment and eligible to the IT infusion system implantation if the test provided a pain relief =50%. Patients not responder were considered not eligible to permanent intrathecal morphine infusion with IDD.

Patients with a successful trial period underwent the implantation of a permanent IT morphine delivery system a month later.

All the surgical procedures were performed by the same physician (GD) using local anaesthesia with an intravenous sedation, with the patient in the right lateral position, and IT catheter was introduced at L3-L4 level and advanced under fluoroscopy with the tip at T8-T10. The catheter was sutured to the prevertebral fascia and subcutaneously tunnelized up to the left side of the abdomen, where a subcutaneous pocket was created for the pump (Synchromed II 20mL, Medtronic INS, Minneapolis, MN, USA). The initial IT morphine dose was set and scaled according to the effective trial dose for each patient, considering the ratio 1mg epidural: 0.1mg intrathecal, in order to avoid adverse effects secondary to morphine overdose. The administered dose was then modified during every visit in order to obtain a pain relief = 50% [10,11].

Patients were assessed at the baseline and at 6, 12 and 24 months (mo) follow-up visits (FU) with VAS score for pain intensity and with 3 different standardized questionnaires (Oswestry Disability Index, EQ-5D and SF-36) for functional abilities and quality of life.

The Oswestry Disability Index Questionnaire (ODI) evaluates the impact of pain on daily activities. The index has been shown to be sensible in patients’ functional status changes and it well differentiates improvement and non-improvement [12,13]. The Oswestry disability index is based on ten items, each followed by six alternatives [14]. Each question is scored from 0–5, and the sum of the scores is then expressed as a percentage.

The Short Form-36 Health Survey (SF-36) is an indicator of patients’ overall health status. It includes 36 questions that form 8 scales: AF-physical activity (10 items), RP-role limitations due to physical health (4 items) and RE-role limitations due to emotional problems (3 items), BP –bodily pain (2 items), GH-perception of general health (5 items), VT vitality (4 items), SF-social activities (2 items), MH-mental health (5 items) and a single question about changing in health status [15].

The EuroQol (EQ-5D) is a standardised instrument for use as a measure of health outcome that includes five dimensions: mobility, self-care, usual activities, pain, anxiety/depression. For each dimension, the questionnaire investigates whether the person suffers from serious, moderate or no disabilities. The questionnaire also includes a visual analogue scale from 0 to 100 on which the patients indicate the level of perceived health status. Adverse events were also recorded in order to investigate the safety of the therapy [16].

Patient’s satisfaction was evaluated with direct questions with multiple choice: very unsatisfied, little unsatisfied, little satisfied and very satisfied.

Statistical analysis

Collected data were analyzed to assess the baseline characteristics and changes from baseline to FU. The software used for statistical analysis was STATA/SE 12.1 (StataCorp, College Station, TX, USA). All new generated variables and descriptive and analytical procedures developed in STATA were saved in a file of code “Stata Do-file”. All statistical tests are to be considered 2-tailed and a p-value of 0.05 was considered significant. In case of Quality of Life missing data, the Last-Observation-Carried- Forward (LOCF) method was used.

Continuous data were expressed as mean and standard deviation, median with 1st-3rd quartile and range while categorical variables were expressed as absolute number and percentage. Percentages will refer to patients with available information (N).

Comparisons between baseline and follow-up data (12 or 24 months) and between the two follow-up data were evaluated with Student t-test for paired samples, if the distribution was Gaussian, or with Wilcoxon sign rank test otherwise.

Normality was assessed by a Shapiro–Wilk test. Homoscedasticity was evaluated by an F test for the homogeneity of variances. All 2-tailed p value <0.05 was considered statistically significant.


44 patients (33 females and 11 males) with nociceptive prevalent pain, mean age of 70.6 + 12 years (range: 40 – 87 years) with severe intractable chronic pain have been implanted after positive response to trial test and followed up to 24 mo FU.

Pain areas were back and legs in 46% of patients, back and one leg in 36% or legs in 18%. The primary etiology of pain was FBSS in 40.9% of cases, spondylodiscartrosis 20.5%, spinal stenosis in 18.2% and osteoarthritis in 13.6%. Time from pain onset to implant was 69.0 + 56.8 (range: 5 months – 25 years) and all patients had already made opioids rotation and at the baseline the pharmacological treatment was: morphine sulfate (55% of cases), buprenorphine (27%), oxycodone (27%) and fentanyl (9%).

Furthermore 36% were treated with anticonvulsants, 18% wit NSAIDs and 9% with antidepressants (Table 1) 64% of the patients also underwent previous treatments as: rehabilitation (20.5%), nerve blocks (6.8%), TENS (6.8 %), eperidurolysis (4.6%) and magnetic therapy (2.3%).