My Journey to Ketamine in Chronic Pain Management

Introduction

My journey into the use of intrathecal (IT) ketamine for chronic pain began in the late 1990s, driven by curiosity and clinical inquiry. This article explores the background, studies, and toxicity concerns related to IT ketamine, emphasizing its potential in chronic pain management, particularly for cancer-related pain.

Early Clinical Observations

I first encountered IT ketamine infusions being administered at doses of 50 to 200 micrograms per day for non-malignant chronic pain. Intrigued, I sought clinical justifications and consulted experts like Dr. Lisa Stearns, a notable advocate for IT ketamine in cancer pain management. Dr. Stearns frequently used IT ketamine in the last 90 days of life for her patients, considering it an essential option.

These early inquiries and subsequent clinical observations solidified my belief in ketamine's viability as a chronic pain reliever, especially in cancer patients. While IT ketamine for non-malignant chronic pain remains rare due to limited studies and toxicity concerns, low-dose infusions (<200 mcg/day) have shown effectiveness without significant side effects.

Ketamine Hydrochloride

Ketamine, approved by the FDA in 1970, acts as a noncompetitive antagonist of the NMDA receptor for glutamate, a key neurotransmitter in the central nervous system (CNS). Initially used as an anesthetic induction agent (1-4.5 mg/kg IV), ketamine exists in two enantiomers: S and R. The S enantiomer, with higher potency due to its affinity for PCP binding sites on the NMDA receptor, is favored. Structurally related to phencyclidine, ketamine has a lower incidence of hallucinations and minimal respiratory effects. It can desensitize excitatory receptor systems in the CNS, although it may produce dissociative sensations exploited for non-medical use. Other effects include elevated blood pressure and bronchodilation.

Existing Studies

The Polyanalgesic Consensus Guidelines (2017) reference IT ketamine for chronic pain. Key studies include:

• Sator-Katzenschlager et al.: Treated a patient with chronic pain using IT ketamine (31.5 mg/day initially, increased to 47.2 mg/day) alongside morphine. The patient experienced significant pain relief without psychotropic or neurological side effects .
• Bernath et al.: Treated neuropathic pain from urethral carcinoma with IT ketamine (22.5 mg/day), morphine, and clonidine. The patient reported satisfactory pain relief over 10 weeks without arterial hypertension or psychomimetic alterations .
• Vranken et al.: Used IT ketamine (40 mg/day) for a patient with neuropathic cancer pain, achieving significant pain relief in the last three weeks of life without observable toxicity .

These studies, though limited to end-of-life treatment, highlight ketamine's efficacy in cancer pain where other treatments fail. Additionally, low-dose IT ketamine for non-malignant chronic pain has shown great pain relief without side effects.

Intrathecal Ketamine and Toxicity

Toxicity concerns regarding IT ketamine are often cited but are not well-documented. Some case reports indicate histological changes, but the precise causes are unclear, often attributed to preservatives or other agents used in combination with ketamine:

• Stotz et al.: Reported histological changes in medullary tissues at 67.2 mg/day without necrosis or demyelination .
• Karpinski et al.: Observed subpial spinal cord vacuolation in a terminally ill patient at 5 mg/day, though the exact cause was uncertain .
• Malinovsky et al.: Noted spinal cord lesions in rabbits, but the role of ketamine versus its preservative remained undetermined .

These findings suggest a need for caution, but they also highlight the potential benefits of ketamine when used appropriately.

Conclusion

Engaging with physicians about their IT-prescribing habits reveals diverse approaches to chronic pain management. For suitable patients, ketamine is an effective option, often met with intrigue despite initial reluctance. Its intravenous counterpart is widely accepted in pain management, and we hope this article fosters curiosity about IT ketamine for chronic pain treatment, whether malignant or non-malignant.

For more insights and detailed studies, refer to the Polyanalgesic Consensus Guidelines and related case reports on IT ketamine use in chronic pain management.

References

1. Deer et al: The Polyanalgesic Consensus Conference (PACC): Recommendations on Intrathecal Drug Infusion Systems Best Practices and Guidelines. Neuromodulation 2017; 20: 96-132.
2. Sator-Katzenschlager, S et al: The Long Term Antinociceptive Effect of Intrathecal S (+) Ketamine in a Patient with Established Morphine. Anesth Analg 2001; 93: 1031-4.
3. Bernath, J et al: Long-term intrathecal S (+) ketamine in a patient with cancer-related neuropathic pain. BJA 2005; 95(2): 247-9.
4. Vranken JH: Treatment of neuropathic cancer pain with continuous intrathecal administration of S (+)-ketamine. ACTA Anaesthesiol Scand 2004; 48: 249-52.
5. Stotz, M, Oehen, H, Gerber, H: Histological Findings After Long-Term Infusion of Intrathecal Ketamine for Chronic Pain: A Case Report. J Pain and Symp Management. 1999; Vol 18 No. 3: 223-8.
6. Karpinski, N et al: Subpial vacuolar myelopathy after intrathecal ketamine: report of a case. Pain 1997, 73: 103-5.
7. Malinovsky, J: Is Ketamine or Its Preservative Responsible for Neurotoxicity in the Rabbit. Anesthesiology 1993; V 78 No. 1: 109-15.

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