Background & Aims
Patients with head and neck cancers experience significant pain. (1) Previous studies suggest pain may arise secondary to tissue damage multiple sources such as mucosal injury, invasion of the tumor into somatic tissue (skin, muscle, bone) with inflammation or ischemia, and nerve infiltration or compression, resulting in both neuropathic and nociceptive pain. (2,3) Ketamine is a dissociative anesthetic that works as a N-methyl-D-aspartate (NMDA)-antagonist. The NMDA receptor has a broad role in the activation and maintenance of pain states. (4) Literature recognizes the administration of ketamine at subanesthetic doses provides analgesic benefits in patients with chronic pain and cancer-associated pain with limited side effects. (5,6) Ketamine can reduce opioid burden in oncological settings, but limited research exists specifically for head and neck cancers (HNCs).
Methods
We explored the use of ketamine in end-of-life care for a patient cared for by the palliative care department at an urban, academic medical center in Boston, MA, USA. Ms. R was a 62-year-old, retired pharmacist with HNC requiring radiation and multiple surgical resections. She was referred to palliative care following cancer recurrence. Initial pain management included oral lidocaine and oxycodone. When meeting palliative care, she discussed goals-of-care and symptom management, noting medication sensitivities including intolerance and history of psychosis with opioids, even at small doses. Thus, she underwent rotation to low-dose methadone with symptom improvement but was resistant to dose increases. Palliative care introduced potential of ketamine for pain, and the decision was made to undergo outpatient trial of ketamine with close observation.
Results
Oral administration of 40mg of ketamine allowed for better pain control lasting 3 to 4 days, and changed her overall pain experience. Shortly after the trial with ketamine, she started oral ketamine at home to control pain secondary to growing oral tumor. Over two months, her ketamine requirement increased from 10mg twice weekly to 100mg every four hours in combination with increasing methadone doses. Her family was committed to take care of her at home. In her final weeks of life, she experienced a pain crisis secondary to a pathological jaw fracture which was managed using subcutaneous, intermittent ketamine. This adjustment of ketamine stabilized her comfort level again. In her final days, she achieved her goal of being preset with her family, which included playing cards, and she died peacefully at home.
Conclusions
Ketamine is effective in managing treatment-resistant pain in HNCs. The oral cavity is a richly innervated area in the body. Thus, it is likely that that ketamine, a strong NMDA receptor antagonist with opioid receptor activity, has high nerve penetration within the oral cavity. Side effects may be more tolerable than those observed when relying solely on high-dose opioids. Limited data exists on ketamine use for HNC-related pain at the end of life.
References
1.Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics. CACancer J Clin. 2008;58:71–96
2.Woolf CJ, Mannion RJ. Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet. 1999;353:1959–64.
3.Epstein JB, Wilkie DJ, Fischer DJ, Kim YO, Villines D. Neuropathic and nociceptive pain in head and neck cancer patients receiving radiation therapy. Head Neck Oncol. 2009 Jul 14;1:26.
4.Fisher K, Coderre TJ, Hagen NA: Targeting the N-methyl- D-aspartate receptor for chronic pain management. Pre- clinical animal studies, recent clinical experience and future research directions. J Pain Symptom Manage 2000;23: 358–373.
5.Kronenberg, R. H. (2002). Ketamine as an analgesic: parenteral, oral, rectal, subcutaneous, transdermal and intranasal administration. J. Pain Palliat. Care Pharmacother. 16 (3), 27–35. doi:10.1080/J354v16n03_03
6.Bell, R. F., Eccleston, C., and Kalso, E. A. (2017). “Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database Syst. Rev. 2017 (Issue 6), CD003351. doi:10.1002/14651858.CD003351.pub3
Presenting Author
Tamara Vesel
Poster Authors
Topics
- Specific Pain Conditions/Pain in Specific Populations: Orofacial Pain