Up to 60% of patients with advanced cancer experience pain from progressive illness, with prevalence increasing to 80% at terminal stages of disease. While distress associated with cancer pain may be alleviated with the analgesic ladder, some patients continue to suffer unrelieved pain or adverse effects of treatments prescribed. Their pain is described as intractable or refractory, and is frequently unresponsive to escalating opioids. Change in routes of administration, opioid rotations, adjuvants such as antidepressants and anticonvulsants, steroids, and ketamine may have been tried, with unsatisfactory outcomes. Also nerve blocks and intrathecal infusions were most likely considered or have failed.
Lidocaine either intravenously (IV) or subcutaneously (SC) appears as a promising approach for the control of complex cancer pain.
It is an amide local anesthetic and class 1B antiarrhythmic agent; its pharmacological effects are achieved through nonselective blockage of voltage and frequency-dependent sodium channels on nerve membranes. Apart from direct sodium channel blockade, findings indicate additional antihyperalgesic and anti-inflammatory actions.
Pain and palliative physicians have administered lidocaine in multiple ways, including slow bolus (single or repeated), continuous infusion (over varying periods), or a combination of both (the initial bolus often determines if an infusion follows).
Acknowledging a steep dose-response curve, observation has shown both a minimum threshold drug level before benefits and a narrow therapeutic index with risks of neuromuscular and cardiac toxicity. Practically all initiations of parenteral lidocaine are performed in the institutional setting under close monitoring.
This may include a baseline electrocardiogram, laboratory tests, and continuous nursing observation throughout drug administration.
These requirements excluded patients from being treated outside the hospital, until recently.
Observational studies show parenteral lidocaine has been used successfully without severe adverse events within the community, whether in an inpatient hospice or home, and was recommended as second- or third-line intervention to manage different types of complex cancer pain in patients of all ages. Patients were able to achieve symptom control and eventually died outside the acute hospital setting. These are encouraging findings for pain patients with conventional therapies (e.g., opioids and adjuvants) that fail–in these cases systemic lidocaine appears to be a feasible, effective, and safe option.
Systemic lidocaine, whether administered IV or SC through slow bolus or continuous infusion, has characteristic benefits in cancer pain insufficiently controlled with opioids or adjuvants. With a half-life of 90 to 120 minutes, it is rapidly distributed systemically before hepatic metabolism and renal excretion. While half-life can increase with infusion beyond 24 hours, drug levels decrease equally rapidly after administration is stopped (less than an hour after continuous infusion for 3 days). Efficacy is noted precipitously once the drug level reaches a “break point,” with adverse effects noticed soon after—characteristic of its narrow therapeutic index. Rapid onset of action not only brings prompt relief in a pain crisis, but it is also critical when a patient's prognosis is short. Lidocaine demonstrates a potential for durable analgesia after “bursts” of systemic drug administration beyond its limited half-life. This implies drug-free periods without round the clock medications, or minimally opioid or adjuvant drug sparing, with adverse effects lessened while comfort is preserved. Without tolerance encountered or anticipated, infusions may be repeated as needed.
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Adapted from Chong PH, Yeo ZZ. Parenteral Lidocaine for Complex Cancer Pain in the Home or Inpatient Hospice Setting: A review and synthesis of the evidence. J Palliat Med 2021; 24(8): 1154-1160.