Department of Anaesthesiology and Intensive Care B, Medical University Vienna, Vienna, Austria. 1 Department of Anaesthesia and Intensive Care, Medical University Hanover, Hanover, Germany
* Corresponding author. E-mail: justus.benrath{at}meduniwien.ac.at
Accepted for publication April 25, 2005.
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Abstract |
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Keywords: anaesthetic administration, intrathecal ; anaesthetic administration, long-term ; anaesthetics i.v., S(+)-ketamine ; pain, cancer-related ; pain, neuropathic
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Introduction |
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We present the successful treatment of a patient with severe cancer-related neuropathic pain by continuous i.t. administration of S(+)-ketamine over 92 days.
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Case report |
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Discussion |
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The patient's pain may have been exacerbated by the development of tolerance to morphine. The dosage of morphine i.t. was increased up to 120 mg day1 and clonidine 360 µg day1 was added but, despite this, neuropathic pain remained. Based on our experience of a patient with opioid tolerance in non-tumour pain we decided to add S(+)-ketamine i.t. to the morphine.5 Continuous i.t. administration provided good analgesia and allowed the progressive reduction of the daily morphine dose without signs of opioid withdrawal.
I.T. ketamine was described 20 yr ago15 but there are only a few reports of continuous i.t. administration. An advantage of the i.t. route is the lower drug dose, which potentially reduces side-effects. In our case, a dose of 22.5 mg day1 was sufficient to treat the neuropathic element of the pain. Initially, doses of up to 50 mg day1 S(+)-ketamine were used, which is similar to that in our recent study where doses up to 47.2 mg day1 were used.5 A dose of 67.2 mg day1 has been shown to cause unwanted side-effects, such as acute psychotic alterations, 7 days after the start of treatment.7 In our case, there were no signs of side-effects, such as arterial hypertension, psychomimetic alterations, or neurological dysfunction, at any time.
There is no pharmacokinetic information on continuous i.t. administration S(+)-ketamine available. In our case, the ketamine dosage remained constant over 11 weeks. No loss of efficacy and no accumulation in the plasma were found (Table 3). The higher concentration seen 2 weeks after the start may be explained by the relatively high doses on days 912 (Tables 2 and 3).
Recent studies and reviews have raised concerns about the neurotoxicity of ketamine suggest that the neurological lesions reported may be caused by the preservatives benzethonium chloride or chlorobutanol used in racemic ketamine solutions.6 16 17 S(+)-Ketamine is a preservative-free formulation and therefore seems suitable for i.t. administration. However, there are no histological studies of the effect of S(+)-ketamine given intrathecally.
Ketamine can be given by a number of other routes including s.c., epidural, i.m., oral, nasal, rectal, and transdermally.18 These are all possible routes for ketamine administration and the treatment of neuropathic pain using i.v. and s.c. routes has been described.18 We used an implanted catheter to avoid the use of an additional long-term device.
In summary, the continuous i.t. administration of the S(+)-ketamine enantiomer proved to be effective in a patient with severe neuropathic cancer pain refractory to conventional pain therapy. The absence of side effects over 3 months together with low plasma concentration favours the i.t. administration of S(+)-ketamine as an option in severe neuropathic cancer-related pain. However, this route of administration should be considered as a last resort, because of the potential for neurotoxicity.
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References |
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