Multimodal intrathecal analgesia in refractory cancer pain
Authors: Mastenbroek Thierry C. , Kramp-Hendriks Bianca J. , Kallewaard Jan Willem , Vonk Johanna M. 
Published: November 2016

Abstract

Background and aims
Cancer pain treatment has improved over the last decades. The majority of this population can be treated effectively with analgesics following the Guidelines of the original World Health Organisation (WHO). Unfortunately 10–15% of these patients still suffer from severe and refractory cancer pain, especially in the terminal phases of disease and require additional pain management modalities. Therefore, end-stage clinical interventions are particularly needed to minimize the perception of pain. With intrathecal therapy (ITT), drugs are delivered close to their site of action in the central nervous system avoiding first-pass metabolism and blood–brain barrier. It may improve analgesia with a smaller dose and possibly achieve a reduction in systemic or cerebral side effects compared to oral supplied medication alone. Multimodal analgesia enables further dose reduction with improved analgesia and fewer side effects.

Methods
In this retrospective research we investigated the effectiveness and side-effect profile of intrathecal morphine, bupivacaine and clonidine. Patients were followed until death occurred. Pain scores and side effects were recorded before initiating ITT (T0), just after initiating ITT (T1), at hospital discharge (T2), in the ambulant setting (T3) and the last obtained scores before death occurred (T4).

Results
Nine patients were included who suffered from severe and refractory cancer pain, not reacting to conventional pain management or had intolerable side effects. Primary tumour location was pancreatic (4), urothelial (3) and prostate (2). Primary pain was considered neuropathic or mixed neuropathic-nociceptive. The treatment team consisted of an anaesthetist, specialized nurse in coordination with primary physician, treating oncologist and specialized home care.
All patients were free of pain after initiation of the intrathecal therapy. The average follow-up period was 11 weeks in which there was a slight increase in NRS-score. In the last days before death occurred, half the patients were still free of pain. There were no problems during insertion of the catheter, device malfunction or infection. No severe adverse events defined as hypotension requiring inotropes, respiratory depression or neurological deficits were observed. Three patients experienced mild hypotension which gradually decreased after clonidine dose adjustment. Lower extremity weakness occurred in three patients as well. After bupivacaine dose adjustment the weakness disappeared in two patients and in one patient the lower extremity weakness persisted as a result of conus compression by tumour.

Conclusion and implications
Multimodal IT treatment with morphine, bupivacaine and clonidine is effective and safe for treating refractory cancer pain in the terminal phase of disease.
The study offers an important contribution to literature where there is still lack of convincing evidence about the benefits and harms of this type of pain management in patients with otherwise refractory cancer pain.