Odin is a 6-year-old, neutered, male Great Dane who presents for ongoing management of a presumed osteosarcoma of the left distal tibia. He is systemically healthy and the primary complaint is related to pain, swelling, and lameness in this limb. At this time, his owners are interested in pursuing alternatives to amputation for controlling Odin’s pain. Five months ago he received a single fraction of Cyberknife therapy to this lesion and has since been treated with chemotherapy and pamidronate. He initially did well with a special brace for support of this limb, but recently has become too painful to tolerate the brace and his mobility has significantly decreased. The limb remains intact with no evidence of fracture on radiographs. Current pain therapy includes Rimadyl, tramadol, and acupuncture which he has tolerated well but is becoming less effective.
On examination, there is an enlarged area just above the left tarsus. This is significantly painful to palpation with hyperesthesia/allodynia of the upper thigh and lumbar epaxial musculature. He refuses to stand without significant aid and will not place weight on or lie on his left side. No other areas of pain are identified.
Amputation was discussed but declined in favor of palliative care. Goals for pain management are multifactorial but center around the ability to improve mobility in this large dog to enable the owner to care for him and allow fitting and use of the brace in order to help avoid fracture.
Partly due to the severity of his presentation, but also due to the need to rapidly restore some mobility due to his large size, a hospitalized “pain vacation” was elected for Odin in addition to adjustments to his long-term analgesic protocol. A “pain vacation” consists of an aggressive and multimodal injectable treatment for 12-24 hrs. Medications are designed to treat pain related to the direct lesion while also dramatically calming central hypersensitivity to pain. The goal is to achieve a rapid and potentially long lasting “reset” of central pain centers while also achieving more rapid control of hypersensitivity surrounding the lesion itself.
Odin was hospitalized and treated with lidocaine, ketamine, and dexmedetomidine as IV constant rate infusions. No loading doses were used. Lidocaine and ketamine were titrated to their desired doses over the first hour. Dexmedetomidine was titrated to achieve a relaxed, conscious, non-anxious patient. A single dose of methadone was given initially to offset the pain of hospital manipulations and IV catheter placement. Infusions of lidocaine, ketamine, and dexmedetomidine were continued for 12 hours.
Odin became rapidly more comfortable during treatment. By the end of the infusion period, he was able to lie comfortably on and have the affected limb palpated. He was able to stand with aid. He tolerated all medications well and was discharged without incident. At 4 weeks follow-up Odin continued to be significantly more comfortable. He is able to toe touch and balance on the affected limb and comfort continues to be maintained with oral medications.
Lidocaine blocks sodium channels in central and peripheral nerve cell membranes that play roles in acute and persistent pain hypersensitivity. It may also inhibit calcium channels involved in chronic pain conditions. IV dosing in dogs is generally well tolerated with common adverse effects including loss of appetite, nausea, and vomiting.
Ketamine is a non-competitive antagonist at excitatory NMDA receptors. Activation and upregulation of NMDA-R occur with ongoing neuronal depolarization, as in this case of an ongoing painful lesion, and leads to increased excitatory neurotransmission and hypersensitivity. Decreasing these responses can produce sustained increases in comfort and response to more traditional medications. Adverse effects may include tachyarrhythmias, agitation, and nausea.
Dexmedetomidine is an alpha-2 adrenoceptor agonist which produces analgesia via changes in calcium ion communication through sensory pathways in the peripheral and central nervous systems. It is a useful adjunct when titrated to low doses producing mild sedation and anxiolysis and may have a role in reducing central pain hypersensitivity. Adverse effects may include bradyarrhythmias, nausea, and vomiting.
While not a substitute for traditional palliative options in painful cancer, a multimodal “pain vacation” can be an effective adjunct in extending quality of life and achieving rapid improvement in painful states while allowing traditional therapies to resume or maintain effectiveness.
Submitted by Jeff Wilson, DVM, DACVAA, CVMA