Nov
26
2008

New research could change the way post-operative analgesia is administered in dogs, enabling patients to go home sooner and spend less time in the hospital. A study led by the University of Wisconsin-Madison’s School of Veterinary Medicine looked at the effectiveness of injecting dogs with extended-release opioids to provide long-term pain relief. 

The group of scientists, headed by UW veterinary anesthesiologist Lesley Smith, DVM, DACVA, used liposome-encapsulated hydromorphone made with dipalmitoylphosphatidylcholine and cholesterol (DPPC-C hydromorphone) for the study. Different concentrations of the formulation, created at the university, were subcutaneously injected into healthy beagles. The concentration of hydromorphone in the dog’s blood serum was then measured at various intervals to determine whether the drug was working.

“We extrapolated that certain serum levels (as shown in human studies) are correlated with surgical analgesia,” Smith said.

The liposome encapsulation allowed the drug to be released into the dog’s bloodstream more slowly than conventional formulations of the same drug, the study found. Therefore the pain relief lasted longer, eliminating the need for repeated injections or constant rate infusions (CRI) of pain medications after surgery.

“Theoretically, if the animal did not need to be closely monitored for reasons other than pain, it could go home sooner,” she said.

In order to achieve an effective level of analgesia in dogs using conventional hydromorphone formulations, doses must be administered every two hours. However, with the liposome-encapsulated formula, the team found that one subcutaneous injection provided serum concentrations associated with adequate analgesia for 72-96 hours.

The dogs did experience some side effects that were typical of opioids, Smith said, such as panting, mild bradycardia and nausea. But, Smith said the dogs “tolerated these side effects with no untoward outcomes.”

PROMISING IMPLICATIONS

Pain specialists said they thought the study was a “promising” addition in the study of pain relief.

“Pain guidelines are an evolving practice,” said James E. Hagedorn, DVM, DABVP, a member of AAHA’s pain management guidelines task force. “Any addition to the tools we have to manage pain is welcomed.”

Patrice M. Mich DVM, MS, DABVP (canine/feline) is a post-doctoral fellow in Integrative Pain Medicine at Colorado State University’s College of Veterinary Medicine and Biomedical Sciences, and a member of Peak Performance Veterinary Group, an anesthesia and analgesia specialty practice in Longmont, Colo.. She said the method used in the study is “potentially very useful.”

“Since transdermal opioids have proven erratic in their absorption profile, the use of an injected, sustained-release product holds promise,” she said.

However, Mich noted that there are also potential downsides to the protocol, including possible adverse response to opioids. Such a reaction could be very problematic with a drug that stays in the dog’s system for days. 

“With this formulation you cannot ‘get the drug back’ and reversal would likely require hospitalization on a CRI of a reversal agent such as naloxone, as there is no liposome-encapsulated opioid antagonist,” Mich said.  

Other possible dangers could include opioid tolerance; opioid-induced hyperalgesia; improper dosing; and other factors that could alter liposome integrity, thereby delaying or accelerating drug absorption.

But overall, Mich said the study was well-done by a group of researchers that is highly respected in the field.

“This is a welcome development in the area of veterinary pain management,” Mich said.

NEXT STEPS

Smith said clinical trials began in August to test the post-operative analgesic efficacy of liposome-encapsulated hydromorphone in dogs who are undergoing limb amputation. She said if the clinical trials of the DPPC-C hydromorphone formulation show that it is as effective as other methods of post-amputation pain-relief (such as intravenous fentanyl), then the injection could revolutionize pain management for such patients. 

“A single dose of DPPC-C hydromorphone is convenient and does not require special equipment, intensive monitoring, or expertise, making it an accessible analgesic option for many practicing veterinarians,” Smith said.

Smith’s lab is also working on another formula that could provide even longer-lasting pain relief.

“We have a second formulation of liposome-encapsulated opioid that looks like it persists in the serum for 21 days,” she said. “We have not started analgesic testing for that formulation yet, but if it proved analgesic for 21 days, then a dog would only need an injection every three weeks.”

The researchers published their findings in the October edition of the Journal of Veterinary Pharmacology and Therapeutics. The study is titled “Pharmacokinetics of a controlled-release liposome-encapsulated hydromorphone administered to healthy dogs.”

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