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Chronic
nonmalignant pain significantly reduces function and quality of life of
patients affected by it.
Subanesthetic,
subcutaneous ketamine infusion therapy was significantly effective,
well-tolerated and also reduced the use of opioids in patients with chronic
nonmalignant pain
Chronic nonmalignant
pain significantly reduces function and quality of life of patients affected by
it. The pain needs to be adequately managed to avoid further complications.
Neuropathic pain (NP) is one of the common occurrences in such patients and
patients fail to improve with traditional pain killers and opioids. NP is
caused due to nerve damage and patients usually experience spontaneous pain,
hyperalgesia and allodynia.
Ketamine is general
dissociative anaesthesia, mainly used in minor surgical and diagnostic
procedures. It acts centrally as well as peripherally. It is primarily an NMDA
receptor antagonist but also plays a role in the inhibition of Na+ and K+
channels and reuptake of dopamine and serotonin. It has also shown some effects
on α-amino-3-hydroxy-5-methyl-4- isoxazole propionic acid and kainate and γ
-aminobutyric acid receptors. Chronic noxious input to the dorsal horn cells
causes magnesium removal from the NMDA receptors and their activation by
glutamate. Hyperalgesia and allodynia are caused by the prolonged
depolarization of spinal neurons resulting in central sensitization. Ketamine
binds to NMDA receptor and reduces NMDA-mediated nociceptive responses in
dorsal horn neurons. Ketamine may reduce pain by antagonizing NMDA receptors,
reduces tolerance of opioids, improves the sensitivity of opioid receptors and
overcomes opioid-induced hyperalgesia.
Currently, oral or sublingual ketamine formulations are not available for commercial use, but compounding pharmacist may formulate it. Previous research has suggested the superior bioavailability of sublingual formulation (40%) as compared to the oral formulation of ketamine. In both the routes, the analgesic activity is attributed to its metabolite, norketamine. After oral and sublingual administration, the ratios of mean norketamine/ketamine area under the plasma concentration-time curve from baseline to 8 hours were 2.1 and 5.
Rationale behind research: Despite
of being in use for many years for pain management, the long term effectiveness
of ketamine has not been tested for the management of chronic nonmalignant
pain.
Objective: The
present prospective non-randomized non-blinded study was conducted to evaluate
the effectiveness, toxicity and reduction in opioid use after administration of
subanesthetic subcutaneous ketamine infusion therapy in chronic nonmalignant
pain management.
Study Outcomes:
Baseline: Patients’
demographic characteristics, pain site, pain duration, pain intensity, use of
opioids and other analgesics were assessed at the baseline.
Outcomes:
Time Points:
Outcomes:
Figure 1: Reduction in
pain intensity measured by the NRS before and after ketamine infusion
Figure 2: Reduction in
opioid dose before and after ketamine infusion
The patients who responded well to the inpatient
infusion therapy were given ongoing maintenance with sublingual ketamine
lozenges 100 mg (commencing dose: 25 mg three times a day). These subjects were
followed up by a telephone consultation questionnaire between 3 months and 2
years. Patients (31%) who used lozenges post ketamine infusion did not consume
opioids compared to 6% patients not on lozenges. 11% of the total patients who
declined lozenges had increased their dose of opioids.
The present study
demonstrated long term efficacy of subanesthetic subcutaneous ketamine infusion
therapy for treating chronic nonmalignant pain. The study also reported that
ketamine was well-tolerated and caused a significant reduction in the use of
opioids.
There is a lack of
published evidence supporting the long-term use of opioids in chronic
nonmalignant pain. Also, presently available medications are not sufficient
enough to manage pain in the context of central sensitization. Ketamine
infusion therapy could be valid for those patients who have failed numerous
pharmacological and cognitive-behavioural therapy options. Ketamine lozenges,
on the other hand, were able to reduce the use of opioids in this class of
patients. Overall, ketamine infusion therapy as well as ketamine lozenges, both
demonstrated effectiveness in treating chronic nonmalignant pain without
considerable adverse effects. However, to study the importance of treatment
effect shown by ketamine lozenges, blinded RCTs are required to be conducted.
Journal of pain & palliative care pharmacotherapy
Subanesthetic, Subcutaneous Ketamine Infusion Therapy in the Treatment of Chronic Nonmalignant Pain
Olfat Zekry et. al
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