Background

In the last few decades, there has been a growing number of patients diagnosed with some form of chronic pain. The treatment of chronic pain has historically been based on a trial and error approach using antidepressants, anti-epileptics and opioids. Irrespective of treatment, effectiveness of treatment was usually limited to 30-40% of chronic pain patients showing adequate to good pain relief. The remaining population either showed no effect or responded poorly to standard treatment.

Ketamine is an agent which has historically been used in anaesthesia and analgesia. It was synthesised in the early 1960’s as a safer alternative to the drug phencyclidine (PCP or Angel dust) to which it is structurally related. Over the last decade, it has been increasingly used to treat patients with chronic pain, especially those with neuropathic pain, i.e. neural in origin as we know it causes profound analgesia and anaesthesia at low to high doses.

Pharmacology

Ketamine is a NMDA receptor antagonist which is its primary action. It is also thought to modulate opioid and muscarinic receptor activity.

Route of administration: may be administered intravenously (major route of administration, subcutaneously, intramuscularly or orally (though limited by poor effect when administered orally as a large proportion is metabolised by the liver).

Onset of effect: Ketamine had a rapid onset of action when administered intravenously, though the duration of effect is only 10 minutes after administration is ceased.

Half-life: Ketamine has a short half life of 10 minutes which is usually due to redistribution from the brain to peripheral tissues.

Side Effects:

• CVS: Hypertension, Tachycardia
• GIT: Nausea and Vomiting, increased salivation
• Liver: Hepatotoxicty (rare)
• CNS: Hallucinations, Amnesia, Anxiety
• Cutaneous: rash in 15% of patients; pain on injection.

Ketamine and Chronic Pain

Current interest on ketamine focuses on it’s ability to alleviate chronic pain, especially when the chronic pain has a neuropathic component. Table 1 illustrates some of the conditions for which ketamine has been shown to be effective. There is no consensus on the administration protocol and the one I have incorporated at Waverley is one that has been utilised successfully at Beleura and Frankston Hospital by Dr Murray Taverner and shown to be quite effective. While most studies show that short term ketamine infusion is indeed associated with pain relief during infusion only a few studies examined the prolonged effect of ketamine following infusion. Given its side-effects and the high cost of inpatient treatment, I believe that it is imperative to induce sustained analgesia and not just induce analgesia during infusion or for a few hours following treatment. In the included protocol, ketamine is slowly titrated every 15 minutes for an 8 hour infusion or every 2 hours in a 5 day infusion till pain is completely ceased as is effectively tolerated by the patient from a side effect profile. As such, it is imperative that clonidine and diazepam be given strictly as charted as these drugs help minimize the incidence of side effects and enable a smother tolerance of the infusion. If side effects do occur, these are usually short lasting because of the rapid half life of ketamine and usually cease soon after cessation of infusion. In these circumstances, it is advisable to administer the Seroquel charted and to recommence the infusion slowly at the lower dose as the primary aim of treatment is long term pain control. I am always happy to be contacted should you have any questions.

List of chronic pain syndromes for which ketamine has been shown to be effective:

• Syndrome Number of studies
• Acute and chronic migraine
• Breakthrough (non)-cancer pain
• Central neuropathic pain
• Chemotherapy-induced neuropathy
• Chronic neuropathic pain (various causes)
• Complex regional pain syndrome
• Fibromyalgia
• Painful limb ischaemia
• Peripheral nerve injury (traumatic)
• Phantom limb pain
• Post-herpetic neuralgia
• Spinal cord injury
• Temporomandibular pain
• Trigeminal neuropathic pain
• Whiplash