Peri-incisional subcutaneous (SC) injection of 4% bupivacaine appeared to reduce incisional pain and had no evidence of local toxicity, according to results of an animal model study published in Pain Medicine.
The analgesic efficacy of an injectable hydrogel carrier (poly[N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide]) containing 4% bupivacaine (SBG004) was evaluated in 18 Yorkshire-Landrace hybrid pigs in 2 separate studies. The pigs underwent 4 longitudinal incisions measuring 4 cm in length that were treated with active or comparator interventions. The active and comparator analgesics were delivered via peri-incisional SC injection or wound filling (WF) methods. Efficacy was determined by incision site mechanical sensitivity with withdrawal from noxious stimuli using an ascending stimulus method up to 168 hours after surgery. Pharmacokinetics of SBG004 was evaluated in 4 rabbits.
Mechanical allodynia at sites treated with SC SBG004 was found to be significantly reduced at all time points through hour 96 compared with treatment with saline, from hours 8 to 96 compared with WF SBG004, between hours 24 and 96 compared with liposomal bupivacaine, between hours 8 and 48 compared with bupivacaine-meloxicam polyorthoester, and from 8 to 72 hours compared with bupivacaine collagen sponge or bupivacaine HCl solution.
Compared with treatment with saline, treatment with WF SBG004 was associated with decreased mechanical allodynia between hours 4 and 8.
After 96 hours, no group differences were observed.
At day 14, SBG004 gel was macroscopically present with tissue-free regions observed in subcutaneous fat. At day 49, the areas with intact gel were no longer observed and had been replaced with granulation tissue and inflammatory infiltrates.
In rabbits administered SBG004 16.5 mg/kg, the average maximum concentration of SBG004 was 41.6±9.7 ng/mL occurring at 18.0±6.9 hours, with a half-life of 82.0±35.8 hours.
A major limitation of this research was the slight variance in dosing of SC SBG004 between studies.
These data indicate that peri-incisional SC SBG004 may be sufficient to provide local analgesia up to 96 hours postoperatively. This administration method had no evidence of histopathologic toxicity up to 49 days after the procedure. In addition, the study authors state that “[t]here was no difference in analgesia provided by any commercially available extended-release local anesthetic compared to plain bupivacaine HCl at any postoperative time point.”
Disclosure: Some study authors are employed by or declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Heffernan JM, McLaren AC, Glass CM, Overstreet DJ. Extended release of bupivacaine from temperature-responsive hydrogels provides multi-day analgesia for postoperative pain. Pain Med. Published online August 30, 2022. doi:10.1093/pm/pnac119