Study Shows Intrathecal Bupivacaine Effective For Long-Term Cancer Pain Treatment

AUTHOR: Michael Vlessides

Anesthesiology News

Patients suffering from cancer pain refractory to systemic opioids may find relief in an unlikely source, according to a pilot study by Swedish researchers: intrathecal bupivacaine. They concluded that the therapy can be effectively used for long-term pain management in these individuals with little increase in dose and few of the side effects that often accompany opioid-related treatment.

“Treating cancer pain with morphine is often effective, but it’s not without its problems,” said Anders Wincent, MD, a senior consultant at the Karolinska University Hospital in Stockholm. “Previously we found there was no analgesic benefit to adding morphine to intrathecal bupivacaine in severe cancer-related pain [Int J Clin Pharmacol Ther 2017;55(6):525-532]. So in this study we wanted to see if we could address this pain only with intrathecal bupivacaine.”

Putting It to the Test

To help answer this question, Dr. Wincent and his co-investigator Karl-Fredrik Sjolund, MD, PhD, enrolled 30 adult patients (17 women; median age, 55 years) with cancer-related pain, who presented to the institution between November 2013 and June 2017, into the longitudinal case series; each was receiving systemic opioid therapy. All patients were started on an intrathecal bupivacaine infusion of 2 mg/mL; flow rates and subsequent bolus doses were titrated as necessary. The catheter tip was positioned cranially to the individual’s most painful dermatome; catheter tip position was verified with fluoroscopy. After subcutaneous tunneling, the catheter was attached to a subcutaneous port and connected to an external pump.

Before intrathecal bupivacaine therapy, the participants completed a pain-related questionnaire. Follow-up was performed by nurses via a structured telephone interview with the patients, their families or staff at a palliative care facility or hospital. Pain intensity at rest and during activity was measured using the numerical rating scale (NRS); other tools included the short form of the Brief Pain Inventory, the revised Edmonton Symptom Assessment Scale and ECOG Performance Status.

As Dr. Wincent reported at the 2018 World Congress on Pain (abstract PST328), the majority of patients saw their systemic opioid dose drop by half as soon as they received the bupivacaine infusion. The NRS pain scores at rest and with activity were well controlled with intrathecal bupivacaine for as long as two months in the 27 patients available for follow-up (Table).

The median last recorded dosage of bupivacaine was 45.0 mg per day (range, 24.0-138.2 mg per day) for the 22 patients who remained on bupivacaine alone. Six patients required the addition of intrathecal morphine (0.1-0.25 mg/mL) on days 12 to 47 of bupivacaine therapy, five of whom were available for follow-up. The median last recorded bupivacaine dosage among these individuals was 81.6 mg per day (range, 24.0-120.0 mg per day). The maximum recorded bupivacaine dosage was 206.2 mg per day; the highest recorded morphine dosage was 9.6 mg per day. One of the patients who received supplemental morphine also received clonidine, at an initial dose of 5 mcg/mL. The median modified Bromage score was 1 at days 1, 7 and 28.

Of note, the researchers found that all patients continued intrathecal therapy until death. The median treatment time for patients only taking bupivacaine was 40 days (range, eight to 334 days), compared with 72 days for those who received supplemental morphine (range, 22-105 days).

The investigators were encouraged by the findings, particularly the fact that the intrathecal bupivacaine dosage only increased modestly throughout the study period. “We also found motor side effects to be limited,” Dr. Wincent said in an interview.

Bupivacaine Alone

“Why start with morphine if you don’t have to?” Dr. Wincent continued. “I imagine there are some centers that use many different drugs right at the start. But why start with so many when you can just start with bupivacaine? Then you can add other agents as necessary later on.”

Although David Craig, PharmD, the lead pharmacist in supportive care medicine at Moffitt Cancer Center, in Tampa, Fla., did not find the results of the trial particularly surprising, he found the researchers’ strategy interesting. “We know that bupivacaine has proven benefits as an analgesic, so it’s not that surprising that they found that cancer patients given intrathecal bupivacaine had pain relief with this strategy,” he said.

“I guess the biggest hurdle with implementing this type of strategy would be availability and costs,” said Dr. Craig, who is a member of the Pain Medicine News editorial advisory board, a sister publication of Anesthesiology News. “In addition, for patients with prolonged life expectancy, this strategy might not be feasible given the necessary equipment needed if using an external pump.”

Yet as Dr. Craig added, it may be too soon for he and his colleagues to incorporate the technique into practice.

“I think we would consider using it, but would have to have some additional ‘comfort’ with using this type of strategy, as it is invasive, could carry additional risks, and requires close monitoring and follow-up, which may present additional hurdles in implementing such a strategy in a clinical setting,” he noted. “There are interventional pain providers that currently use intrathecal bupivacaine as part of a multidrug strategy for cancer and noncancer pain management; however, I’m not aware that they are using this as a single agent like these researchers have described.”