Mercadante, S., Arcuri, E., Ferrera, P., Villari, P., & Mangione, S. (2005). Alternative treatments of breakthrough pain in patients receiving spinal analgesics for cancer pain. Journal of Pain and Symptom Management, 30, 485–491.

Patients with advanced cancer and pain were selected for intrathecal pain management after receiving different trials of systemic opioids. All consecutive patients with cancer pain receiving spinal analgesics were surveyed. They had unsuccessfully received different opioid trials (at least two routes—oral and IV—and two drugs, including fentanyl, morphine, or methadone) resulting in poor analgesia and adverse effects. They were selected for intrathecal treatment versus SL ketamine after receiving different trials with systemic opioids.

Patients received spinal treatment and presented with breakthrough pain, requiring alternative methods, including SL ketamine or intrathecal boluses of local anesthetics. Patients were able to choose between SL ketamine or intrathecal boluses of local anesthetic. Nine patients received intrathecal levobupivacaine boluses. Three patients received ketamine SL.

• N = 12
• KEY DISEASE CHARACTERISTICS: Consecutive patients with advanced cancer and pain

• LOCATION: Acute pain relief and palliative care unit in Italy

• Open clinical trial

• Pain intensity on a numerical scale from 0–10 and symptoms commonly associated with spinal local anesthetic injection (e.g., hypotension, sensory and motor block, bladder dysfunction) were recorded using a scale of 0--3 (absent, light, moderate, severe) at the time of injection, and then followed at one-minute intervals until pain level was less than 50% of the initial value.
• Assessed for adverse effects of ketamine (e.g., confusion, agitation, drowsiness) graded from 0–3 until pain decreased to 50% of the previous level.

Nineteen patients who experienced a mean of 2.4 breakthrough pain episodes per day responded to a mean of 27 mg of morphine IV per episode. Twelve subjects required an alternative treatment. No specific differences were found between these two groups in terms of previous systemic opioid doses or pain mechanisms. In the spinal anesthetic group, the median Karnofsky status at the time of admission was 40. The median breakthrough pain intensity was 9 (range 7--10). All patients received an adequate pain relief (less than 50% of initial pain) within five minutes. In the ketamine SL group, pain was controlled in almost all patients within five minutes. Adverse effects were of low intensity (0–1 of scale used).

• Data on the treatment of breakthrough pain in patients receiving a spinal treatment are lacking, and the use of spinal route for episodic (breakthrough) pain has never been reported.
• This was an open clinical trial with a very selective population.
• Small sample size
• Further studies need to be performed using a controlled trial with appropriate design.
• Patients were able to choose which treatment they wanted.
• Variability in availability of transmucosal drugs
• Tolerance to ketamine could be an issue long-term.

The administration of these drugs may pose some problems associated with sympathetic block and motor or urinary impairment. Local anesthetics typically have an individualized dose-effect relationship with a narrow therapeutic window. These intensive treatments should be reserved for a very select population and initiated in an appropriate setting with frequent monitoring facilities and skilled nursing. Spinal anesthesia should be reserved for a select number of patients with the best methods to prevent infection (increased manipulation of catheter).