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Bupivacaine as an injectable suspension for pain control

Gordon-Evans, W. J., Suh, H. Y., & Guedes, A. G. (2019). Controlled, non-inferiority trial of bupivacaine liposome injectable suspension. J Feline Med Surg. 1098612X19892355. 

Careful attention to pain control is an important part of veterinary medicine and surgery. Ovariohysterectomy (OHE; spaying) is amount the most commonly performed procedures in veterinary medicine. Despite the need for pain control post surgically, many barriers to this are in place, including difficulty in owners or veterinary staff in administering medications, systemic side effects of pain medications, or inaccessibility of patients in trap-neuter-return programs. Other barriers to analgesia include access to controlled drugs, and hesitancy to use NSAIDs in some regions and situations. Local anesthetics provide excellent pain control with minimal systemic side effects, but are hampered in efficacy by short durations of action and need for direct application to the site of pain.

Liposomal bupivacaine is a recently developed formulation that slowly releases bupivacaine from the site of administration over a 72h period. The purpose of this study was to determine if a bupivacaine liposomal injectable suspension (BLIS) would be non-inferior and cost effective compared to a standard bupivacaine-robenacoxib protocol in a high volume spay situation.

The study was designed as a prospective, randomized, double-blinded, non-inferiority trial using the Glasgow Copositive Measure Pain Scale as the primary outcome. Patients were shelter cats being spayed as part of a veterinary surgery course. Due to scheduling, patients were only pain assessed for two days post surgically. All cats were G-CMPS assessed by a single blinded investigator the morning after surgery and every 12 hours until 48h post surgically.

All cats were premedicated with buprenorphine 0.24mg/kg SQ, dexmedetomidine 0.005mg/kg IM, and ketamine 5mg/kg IM, induced with propofol, maintained on isoflurane, and had robenacoxib given prior to recovery. An incisional block was performed with either bupivacaine or BLIS, with half the drug administered under the rectus sheath on both sides of the incision after linea alba closure, and the other half after SQ closure.  Control cats received robenacoxib daily, while treatment cats received saline.

Forty-seven cats were enrolled in the trial, 23 treatment and 24 control. There was no difference between groups in age and weight. Several technical issues occurred regarding timing of administration of drugs and pain scoring. No drug related complications occurred.

Surgical and anesthesia times were not different between groups. G-CMPS scores were low for both groups; median pain score was zero at all times.  There was no significant difference in pain score between groups at any time point. The cost of BLIS was $ 2.80-3.7 USD more than the control group.

The data in this study suggests that there is no difference in efficacy of pain control between a standard bupivacaine-robenacoxib protocol and a liposomal bupivacaine protocol. It may be worthwhile to consider this protocol in high volume or TNR situations where repeated dosing in impractical.

A limitation to this pain control strategy is the lack of analgesia to all potential sites of pain. While the abdominal incision is a potential source of post operative pain, the ovarian pedicles and uterine stump are as well, and this pain would not be addressed by this protocol. Other studies have described the direct application of bupivacaine within the abdomen or to these internal sites with good success. Future work to determine if liposomal bupivacaine is effective by this route is warranted.

The use of veterinary students may also have altered the outcome, as presumably time, incision quality, and surgical technique would be less refined than experiences vets, however this should have been equivalent across groups. There is significant evidence to suggest post surgical pain persists for much longer than 2 days post surgically, and so a longer follow-up would be beneficial. It would also be useful to score pain sooner than the morning after surgery.

Finally, the administration of 0.24mg/kg bupivacaine SQ is known to last for at least 24h, and some studies have indicated the analgesic duration may be longer. As such, this may interfere with the assessment of bupivacaine efficacy. (MRK)

See also:

Vicente D, Bergström A. Evaluation of intraoperative analgesia provided by incisional lidocaine and bupivacaine in cats undergoing ovariohysterectomy. J Feline Med Surg 2018; 20: 922–927.