Mercadante, S., Intravaia, G., Villari, P., Ferrera, P., Riina, S., David, F., & Mangione, S. (2007). Intrathecal treatment in cancer patients unresponsive to multiple trials of systemic opioids. The Clinical Journal of Pain, 23(9), 793–798.

To evaluate patient response to a combination of opioids and local anesthetics administered intrathecally to patients with advanced cancer and to evaluate treating patients with an oral-to-intrathecal-morphine ratio of 100:1, along with required changes in dosage

A cohort of patients with the indicated inclusion criteria received an intrathecal catheter in the operating room under aseptic conditions. The catheter was tunneled subcutaneously to the anterior abdominal wall and connected to a subcutaneous port. Morphine and levobupivacaine initially were started via a syringe pump to provide an infusion rate of 2 mL/h. Levobupivacaine was started at 12.5 mg/d, and morphine rate was calculated from the patient’s daily systemic dose using an oral-intrathecal ratio of 100:1. Doses of each drug were modified as needed to acceptably control pain (about 4 out of 10 on a numeric pain scale), and patients were monitored for adverse effects. Adjuvants, including clonidine and ketamine, were administered intrathecally as necessary. Patients were discharged seven days after the port implantation and converted to a balloon-type device instead of  syringe pump. The balloon-type device was changed every five days. Frequent follow-ups were completed over the phone or in person if possible. Pain and related symptoms were recorded prior to intervention; at hospital discharge; and at one-, three-, and six-month intervals, as well as at least one week prior to death.

• The study reported on 55 patients with advanced cancer. Complete data was available for 45 patients.
• The mean age was 60 years with a range of 33–82 years.
• The sample was 42% female (n = 23) and 58% male (n = 32).
• Patients had undergone previous pain management trials with at least three opioids and two routes of administration (including IV).
• Oral morphine equivalents at baseline averaged 466 mg/d.

This was a single-site study conducted at La Maddalena Cancer Center in Palermo, Italy.

This was a prospective trial.

• Pain intensity was measured using 0–10 numerical scale.
• Opioid-related symptoms, such as nausea and vomiting, drowsiness, confusion, constipation, and dry mouth, were measured using a numerical scale of 0–3 (not at all, slight, a lot, and awful).

• Statistical differences in pain intensity were found with daily dose escalation of intrathecal morphine doses. At the time of hospital discharge and by six months, pain intensity had gone from a mean of 7.98 to 3.0 (p < 0.0002).
• Systemic use of opioids significantly decreased along all measured points of time, up until death, following intrathecal catheter placement for pain control (p < 0.029).
• Symptoms of confusion (p < 0.0001) and constipation (p < 0.008) declined with intrathecal pain management. Early complications, occurring during the hospitalization period, included mild bleeding, headache, and urinary retention requiring bladder catheterization.
• One patient died unexpectedly during admission, and a second patient died after suffering a stroke. No relationship with the use of spinal analgesia was found.
• Two patients developed late complications of local infection. One of these patients required removal and replacement of the catheter.
• One patient developed spinal cord compression and did not proceed with intrathecal treatment.
• Overall, treatment was discontinued in 10 patients for different reasons, but these were not all described.

In patients who have received multiple trials and routes of opioids, intrathecal treatment may provide rapid and long-term relief. An oral-intrathecal morphine conversion ratio of 100:1 and use of local anesthetics may be effective for pain control in highly opioid-tolerant patients with advanced cancer.

• The sample size was small, with fewer than 100 patients.
• Patient and caregiver education was not documented.
• No comparison or control group was included.
• The authors did not discuss breakthrough pain, explain the reasons for all of the discontinuations, or describe the methods of measurement and analysis of complications.

This study was able to demonstrate an effective method and ratio for administration of intrathecal opioids for pain relief in patients with advanced disease. This may provide nursing with additional knowledge regarding appropriate dosages for medication administration, opportunities to develop staff educational sessions on the use of intrathecal catheter maintenance, and educational materials for patients and caregivers. This study suggests that this approach has promise; however, shortcomings in reporting all of the reasons for discontinuation in 18% of the initial sample are problematic. Intrathecal treatment is associated with some complications and caregiving needs for monitoring complications.