Treatment of neuropathic cancer pain with continuous intrathecal administration of S (+)‐ketamine

Abstract

The effective treatment of patients suffering from neuropathic cancer pain remains a clinical challenge. When patients experience either insufficient analgesia or problematic side-effects after opioid administration, intrathecal administration of morphine and other medications such as bupivacaine and clonidine may offer significant advantages. Additionally, ketamine, a non-competitive N-methyl-D-Aspartate-receptor antagonist is able to alter pain perception at the spinal level. Because of the potential neurotoxicity after neuraxial use of racemic ketamine, intrathecal administration of the preservative-free active compound, S (+)-ketamine may be a valuable alternative. In this paper, we present a patient with severe neuropathic cancer pain successfully treated by continuous intrathecal infusion of morphine, bupivacaine, clonidine and S (+)-ketamine. Moreover, quality of life measurements before and 3 weeks after the start of spinal treatment revealed an improvement in pain relief and a higher overall quality of life. No clinical signs of neurologic deficit were observed during spinal treatment with S (+)-ketamine. However, the continuous intrathecal administration of S (+)-ketamine should be considered as the last resort because there are no preclinical safety data with relevant concentrations on intrathecal use of S (+)-ketamine.

Polyanalgesic Consensus Conference 2007: Recommendations for the Management of Pain by Intrathecal (Intraspinal) Drug Delivery: Report of an Interdisciplinary Expert Panel

“…Clinical data suggest that ketamine may be advantageous in treating postoperative and severe intractable pain syndromes that are not alleviated by increasing IT opioid dose escalation (87,88). Continuous IT administration of S(+)‐ketamine in addition to morphine reduced cancer‐related neuropathic pain in a single patient case report (83).…”

Intrathecal Drug Delivery (ITDD) systems for cancer pain

“…In comparison to more conservative delivery methods such as drugs administered orally or intravenously, ITDD is more effective because the medication is directly introduced into the subarachnoid space 8 . The spinal cord is a key anatomical site for pain processing and more specifically the dorsal horn of the spinal cord within the intrathecal space 5, 8 . The advantage of delivering the medication directly into the CSF in smaller dosages is that it may reduce the systemic side effects and the direct delivery to the site of action allows a more rapid and effective response.…”

“…Furthermore, advancement of the disease process can lead to pain or make the existing pain worse. It is difficult to estimate the prevalence of cancer pain because of a lack of standardization in definitions of pain and in the measures used to assess it 5 . The other factor that makes it challenging in estimating the prevalence is the heterogeneity of nociceptive and neuropathic pain conditions 6 .…”

Intrathecal analgesia for refractory cancer pain

“…No serious side effects were seen with this combination, and the total treatment dose of intrathecal morphine was less in the ketamine-treated patients. Vranken et al [ 37 ] described a patient with adenocarcinoma of the cecum who had severe neuropathic pain that was unresponsive to three intrathecal agents over time. The patient fi nally obtained adequate longer-lasting pain relief after continuous intrathecal preservative-free ketamine was added to the regimen.…”