Pain Case of the Month: Brutus—Ketamine Infusion as Part of Multimodal Therapy for Relief of Acute Cervical Pain in a Dog

While ketamine dosages are not an exact science, this case documents the use of a ketamine infusion as a pain management tool for a dog with a neck injury.

Brutus before ketamine infusion. He would not raise his head, but would only move his eyes when his name was called.

by Tamara Grubb, DVM, PhD, DACVAA

Signalment and History

Brutus, a six-year-old, 27-kg male, neutered, mixed-breed dog, was presented for unwillingness to move his neck after jumping to catch a tennis ball.

Physical Exam and
Presenting Signs

On presentation, Brutus was alert and responsive with no abnormalities on the physical exam or neurologic exam other than posture of extended head and neck. On gentle palpation of the cervical muscles, the dog reacted by growling and snarling. The owner reported that this was an unusual behavior for this normally friendly dog. Based on posture, response to palpation, and change in behavior, a pain score of 3/4 on the Colorado State University (CSU) pain scale was assigned. Because of the apparent severe pain, no other examinations of the neck (turning, flexion, etc.) were made. The owner declined referral to a neurology service. The initial options were to begin analgesic therapy and monitor response to treatment or sedate the dog and radiograph the cervical region. The recommendation of imaging was declined and the owner opted for analgesic therapy, which was a reasonable option based on the lack of neurologic abnormalities.

Choice of Therapy

In order to initiate analgesia as rapidly as possible, a carprofen injection (4 mg/kg subcutaneously [SQ]) was administered in-hospital. Gabapentin (10 mg/kg) in a pill pocket was offered to the dog but was refused. The owner stated that the dog ate well at home, so rather than potentially aggravate the neck pain with manipulation for oral pill administration, gabapentin (10 mg/kg per os [PO] three times a day) was dispensed to the owner, along with carprofen (4 mg/kg PO twice a day). In addition to oral medications, the owner was instructed to heat pack the neck with moist heat (i.e., using moist, lightly heated towels) two to four times per day, restrict the dog’s movements and avoid jumping or ball chasing, elevate the food and water bowls, place nonslip rugs or yoga mats in areas where the dog walked, avoid leashes around the neck, and monitor for development of neurologic signs like ataxia or toe dragging.

Twenty-four hours later, the owner reported slight improvement (no pain score from the owner), but within three days, no further improvement occurred. The gabapentin was increased to 20 mg/kg for three days, but again with only mild improvement. Although switching to a different nonsteroidal anti-inflammatory drug (NSAID) could be considered, our experience indicated that expanded multimodal therapy was clearly required for pain resolution, and both pharmacologic and nonpharmacologic options were considered. The pharmacologic options included switching the NSAID to a corticosteroid, adding oral amantadine, applying a fentanyl patch, or adding a ketamine infusion. Because the pain was severe and not rapidly resolving to a tolerable level with standard therapy, a ketamine infusion was recommended to the owner and was accepted. The owner was also offered acupuncture and laser therapy but declined because of the need for frequent visits.

The dog was admitted to the hospital and an intravenous catheter was placed in the right cephalic vein. For the infusion, 25 mg ketamine was added to 110 mL PlasmaLyte in a BURETROL and was administered for four hours at roughly 4 μg/kg/min (1 mL ketamine/fluid per hour). No change was made in the carprofen or gabapentin dosing.

Outcome

The infusion caused no adverse effects. There was no apparent immediate pain relief, but the owner reported moderate improvement within 24 hours, as indicated by increased activity, bending of the neck to retrieve kibbles of food from the floor, and acceptance of gentle petting of the cervical area. However, there was no further improvement for the next 48 hours, so a second infusion was scheduled using the same protocol as the initial infusion. On hospital admission for the second infusion, the dog was a 2/4 on the CSU scale with more, but still limited, cervical mobility and tensing but no growling on cervical muscle palpation. Twenty-four hours after the second infusion, the owner reported that the dog was “almost normal.” Three days after the infusion, the gabapentin was weaned to 10 mg/kg BID and then to 5 mg/kg BID three days later and then was stopped. The carprofen was continued for 14 days because of continued mild muscle pain on palpation. No further neck pain has occurred in the year since the injury.

Conclusion and Discussion

Although no diagnosis was made in this case, because of the history of how the pain was initiated, the site of the pain, and the posture of the dog at presentation, a diagnosis of a cervical acceleration-deceleration, or “whiplash,” type of injury was suspected. These injuries cause damage to a variety of cervical structures and can cause neuropathic pain. Neuropathic pain includes opening of the N-methyl-D-aspartate (NMDA) receptors, and ketamine is an NMDA-receptor antagonist. Although ketamine as an analgesic has recently become mainstream, the drug has been used for decades to treat musculoskeletal pain and is effective in some patients with “whiplash” pain. However, even with more published studies in human medicine than veterinary medicine, a precise, globally effective dose is unknown. The dose used in this report was extrapolated from a 2002 paper by Wagner et al. in which dogs recovering from forelimb amputation received 2 μg/kg/min ketamine postoperatively. Based on the author’s experience, this dose may be ineffective in patients with the degree of pain reported here, so 4 μg/kg/min was chosen.

Intraoperatively, ketamine is often administered at 10 μg/kg/min or higher. However, the higher dose could be more likely to cause adverse effects in conscious patients. Potential ketamine-mediated adverse effects include tachycardia, dysphoria/agitation, and sedation. The loading dose chosen (0.5 mg/kg) was also chosen to avoid adverse effects; however, it is lower than the dose reported in some studies.

In addition, the effective duration of treatment is unknown. Ideally, the infusion would be administered until the patient stated resolution of pain, but that is not possible with animals. The duration chosen in this situation is commonly used in our hospital to accommodate the times of day that the owner can drop off and pick up their pet. Finally, the diluent type and volume were chosen for convenience, as there is no scientific evidence regarding the most effective type or volume.

The total dose of ketamine for the four hours was roughly 430 mg or 4 mL of ketamine. This volume is too small to efficiently administer via infusion pump without dilution. The diluent volume could be small (as the 110 mL chosen here) or large (500–1,000 mL is often used). Thus, although not uncommon, the somewhat slow resolution of pain and need for a second infusion could potentially have been avoided if we had used a higher bolus or infusion dose, a longer-duration infusion, or a different diluent volume or diluent type.

Concerning the other therapies considered as options for this dog, the NSAID was not changed since carprofen/gabapentin did provide some pain relief and since the degree of pain indicated need for multimodal analgesia, not NSAID failure. Steroids were avoided because of their adverse effects, especially increased urination, which would have required this dog to ambulate more. A fentanyl patch was a strong consideration, but dispensing a Drug Enforcement Administration Class II opioid can be concerning.

In retrospect, amantadine would have been a good addition to the protocol following the infusion. The infusion would likely have provided faster onset of pain relief (although no studies have been done to support this theory), but the amantadine would have prolonged the NMDA receptor blockade initiated by the ketamine. This could potentially have shortened the pain duration and may have decreased or eliminated the need for a second infusion.

Finally, the CSU pain scale is designed for surgical pain and is not validated as a pain scale. However, the scale is widely used clinically and has been used extensively by the author. What is more important than the absolute pain “number” at any given moment is change in that number with treatment, which was identifiable in this patient using the CSU scale. In retrospect, a pain scale or quality-of-life scale should have been sent with the owner to use at home.

In conclusion, ketamine infusions are valid additions to analgesic protocols in veterinary patients with difficult-to-manage pain. However, the precise dose of the loading dose and the infusion, as well as the optimal duration of the infusion, are unknown and are likely to be patient and pain level or source dependent, so the need for varied dosing regimens should be expected. The dose reported here may be too low, and the potential adverse effects may be overstated.

In one 2016 study by Kaka et al., conscious dogs subjected to a research model of pain received a
0.5 mg/kg ketamine bolus followed by a ketamine infusion of 30 or 50 μg/kg/min. All dogs exhibited some degree of ketamine-mediated adverse effects (disorientation, salivation, etc.), but the effects dissipated within 20 minutes of infusion cessation and were called “mild and harmless” by the authors. However, the author has not tried that dose.

Discussion by Mike Petty, DVM, CCRT, CVPP, DAAPM

The use of ketamine for the treatment of both acute and chronic pain syndromes is gaining in popularity. Most practitioners are already using it intraoperatively and in the immediate postoperative period as one component of a constant-rate infusion of pain medications that may contain other analgesics, such as an opioid, lidocaine, or dexmedetomidine. In this case, it was used to great effect in the treatment of a nonsurgical acute pain issue.

I first read about the use of ketamine infusions for the treatment of chronic pain in a human pain journal where a study described its being used to treat complex regional pain syndrome, a disease that is usually caused by an injury but with long-standing pain and neuropathic consequences, and that has been reported (rarely) in animals. In any patient with untreated chronic pain, it can be frustrating for the owner and the veterinarian as they wait for standard pain therapies to take effect. An animal who is hospitalized and put on a constant-rate infusion of ketamine by either an infusion pump or a syringe pump can potentially benefit from the “pain vacation” provided by the ketamine by allowing the animal to have a lower pain threshold and hence be more responsive to standard therapies like NSAIDs.

Mike Petty, DVM, CCRT, CVPP, DAAPM, is in private practice in Canton, Michigan. He is a frequent national and international lecturer on topics related to pain management. Petty offers commentary on each Pain Case of the Month.
Tamara Grubb, DVM, PhD, DACVAA, is a diplomate of the American College of Veterinary Anesthesia and Analgesia with a strong focus in pain management. She is an anesthesia/analgesia consultant in small- and large-animal practices, a certified acupuncturist, an International Veterinary Academy of Pain Management member, and an adjunct professor of veterinary anesthesia and analgesia at Washington State University. She is coauthor of two books, Anesthesia and Pain Management for Veterinary Nurses and Technicians (2018) and Analgesia and Anesthesia for the Ill or Injured Dog and Cat (2018). Grubb’s favorite achievement is winning the Carl J. Norden Distinguished Teaching Award.

 

Photo credits: Photo courtesy of Tamara Grubb

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