Liposomal bupivacaine was not associated with increased postoperative complications in dogs receiving closed anal sacculectomy: a retrospective study

Michelle M. Untch BluePearl Pet Hospital, Columbia, SC

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Steven W. Frederick BluePearl Science, Tampa, FL

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 LVT, VTS https://orcid.org/0000-0003-4606-3632
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Deborah Keys Kaleidoscope Statistics LLC, Athens, GA

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Michelle J. Waschak BluePearl Pet Hospital, Columbia, SC

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 DVM, DACVS

Abstract

OBJECTIVE

To compare the postoperative complication rates of anal sacculectomy procedures in dogs treated with or without liposomal bupivacaine (LB).

METHODS

Medical records of 397 client-owned dogs treated with closed anal sacculectomy between 2016 and 2023 were retrospectively identified and grouped on the basis of administration of LB (LB group) or not (non-LB group). Details of short-term (< 15 days) postoperative complications were recorded from physical examination and client communication notes as well as referral documents and compared between groups. Relative risks for complications were calculated. Univariable and multivariable logistic regressions were used to estimate ORs and test for the effects of LB use and other risk factors on complications.

RESULTS

267 dogs received LB and 173 did not. The overall short-term postoperative complication rate in the study was 24% (94 of 397; 95% CI, 20% to 28%), and the short-term postoperative complication rates for dogs in the LB and non-LB groups were 22% (95% CI, 17% to 27%) and 27% (95% CI, 20% to 35%), respectively. The relative risk for overall short-term postoperative complications was 0.80 (95% CI, 0.56 to 1.16), indicating that an association between LB and an increased risk of short-term postoperative complications was not found.

CONCLUSIONS

No significant association of LB with an increase in postoperative complications following anal sacculectomy in dogs was found. Although, LB’s efficacy in these cases was not evaluated.

CLINICAL RELEVANCE

Liposomal bupivacaine may be suitable as a local anesthetic following anal sacculectomy in dogs.

Abstract

OBJECTIVE

To compare the postoperative complication rates of anal sacculectomy procedures in dogs treated with or without liposomal bupivacaine (LB).

METHODS

Medical records of 397 client-owned dogs treated with closed anal sacculectomy between 2016 and 2023 were retrospectively identified and grouped on the basis of administration of LB (LB group) or not (non-LB group). Details of short-term (< 15 days) postoperative complications were recorded from physical examination and client communication notes as well as referral documents and compared between groups. Relative risks for complications were calculated. Univariable and multivariable logistic regressions were used to estimate ORs and test for the effects of LB use and other risk factors on complications.

RESULTS

267 dogs received LB and 173 did not. The overall short-term postoperative complication rate in the study was 24% (94 of 397; 95% CI, 20% to 28%), and the short-term postoperative complication rates for dogs in the LB and non-LB groups were 22% (95% CI, 17% to 27%) and 27% (95% CI, 20% to 35%), respectively. The relative risk for overall short-term postoperative complications was 0.80 (95% CI, 0.56 to 1.16), indicating that an association between LB and an increased risk of short-term postoperative complications was not found.

CONCLUSIONS

No significant association of LB with an increase in postoperative complications following anal sacculectomy in dogs was found. Although, LB’s efficacy in these cases was not evaluated.

CLINICAL RELEVANCE

Liposomal bupivacaine may be suitable as a local anesthetic following anal sacculectomy in dogs.

Introduction

Anal sacculectomy procedures are commonly performed to treat chronic anal sacculitis, tumors of the anal sac, recurrent impactions, anal sac abscesses, and anal sac sinuses.13 While anal sacculectomy generally results in good clinical outcomes, it is not a risk-free procedure. Postoperative complications associated with anal sacculectomy can include surgical site infection, wound dehiscence, fecal incontinence, tenesmus, rectocutaneous fistula formation, suture reaction, scooting, incisional discharge, seroma formation, and anal stenosis or stricture.37 Risk factors associated with postoperative anal sacculectomy complications include performing the standard open anal sacculectomy technique (vs modified open or closed techniques), presence of an intraoperative complication (particularly anorectal wall perforation), dogs weighing < 15 kg, and use of gel to distend the anal sac.35

Liposomal bupivacaine (LB) is a long-acting local anesthetic that is approved for use in dogs undergoing stifle surgery and may provide up to 72 hours of continuous local anesthesia.8 Additionally, extralabel uses following other veterinary surgical procedures, including anal sacculectomy, have been reported.1,911 Despite reports discussing off-label use in anal sacculectomy procedures, the administration technique and clinical outcomes as they relate to the use of LB as a postoperative pain control agent have not been reported. Thus, the impacts of LB on postoperative outcomes following anal sacculectomy are unknown.

The objectives of this study were to describe the administration of LB at the anal sacculectomy surgical site and to compare the postoperative complication rates of anal sacculectomy procedures in dogs treated with or without LB. We hypothesized that there would be no difference in the rate of postoperative complications following anal sacculectomy in cases that received LB compared to those that did not.

Methods

Case selection criteria

Electronic medical records at 2 veterinary referral hospitals (BluePearl Pet Hospital, Columbia, South Carolina, and BluePearl Pet Hospital, Sandy Springs, Georgia) were searched to identify all dogs treated with closed anal sacculectomy procedures between January 2016 and December 2023. The identified medical records were further evaluated, and dogs were sorted on the basis of inclusion and exclusion criteria. Dogs were included if they had undergone a closed anal sacculectomy (unilateral or bilateral), with at least 1 postoperative recheck (≤ 15 postoperative days) with complete medical records (surgical report, postoperative care instructions, and postoperative communication and recheck evaluation notes) available for review. Dogs treated with open anal sacculectomy and/or dogs with incomplete medical records were excluded. Dogs undergoing multiple surgical procedures (ie, anal sacculectomy and abdominal lymph node extirpation) were not excluded from the study.

Medical records review

Dogs were categorized on the basis of use or nonuse of LB (LB group or non-LB group) at the incision site, and relevant case data including signalment, patient weight, clinical signs, diagnosis, laterality, tumor size, and short-term (≤ 15 postoperative days) complications were recorded. None of the dogs in this study received an epidural at the time of surgery. Tumors were categorized as either < 2.5 or > 2.5 cm according to the clinical staging system for apocrine gland anal sac adenocarcinoma (AGASACA) described by Polton et al.12 Clinical signs and complications were documented on the basis of notation in the medical record, and the complications were categorized according to the Clavien-Dindo classification system, which is commonly used to report adverse events following surgical procedures in human medicine (Table 1).13 Additionally, complications were sorted into groups reflecting whether they could be reasonably associated with the administration of LB at the surgical site. Examples of LB-associated complications included surgical site infection, short- and long-term fecal incontinence, self-mutilation of the surgical site, and surgical site dehiscence. Examples of negative outcomes during the postoperative period that could not be reasonably attributed to the use of LB at the surgical site included gastric dilatation and volvulus, systemic metastasis, and aspiration pneumonia.

Table 1

Clavien-Dindo classification of surgical complications.13

Clavien-Dindo classification Definition
Grade 1 Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Allowed therapeutic regimens include antiemetics, antipyretics, analgesics, diuretics and electrolytes, and physiotherapy.
Grade 2 Requiring pharmacological treatment with drugs other than those allowed for grade 1 complications. Blood transfusions, antibiotics, and total parenteral nutrition are also included.
Grade 3* Requiring surgical, endoscopic, or radiological intervention.
Grade 4* Life-threatening complications requiring ICU management.
Grade 5 Death of a patient (including humane euthanasia).

*Categories 3 and 4 were not divided into subgroups.

Liposomal bupivacaine administration

Liposomal bupivacaine (0.4 mL/kg [5.3 mg/kg]) was aseptically withdrawn from the vial into an appropriately sized syringe with a 20-gauge needle immediately prior to use; however, due to the anatomical restrictions of the perineum, the full volume was not used in all cases. The needle was replaced with an unused, sterile 22-gauge needle prior to administration.

Two methods of LB administration were used, depending on surgeon preference. In both methods, the LB was administered into the soft tissues circumferentially around the incision site, providing local wound infiltration anesthesia (Figure 1). However, administration of the LB occurred prior to wound closure in some cases and was performed percutaneously after wound closure in other cases (Figure 2).

Figure 1
Figure 1

Illustration of local wound infiltration with liposomal bupivacaine (LB). A sterile, unused 22-gauge needle was inserted 0.5 to 1 cm into the subcutaneous tissue plane dorsal to the incision and guided circumferentially around the surgical site. The syringe was aspirated to ensure negative pressure and avoidance of intravascular administration prior to injection. The needle was then slowly withdrawn, administering LB into the subcutaneous tissue. The process was repeated until circumferential administration was achieved.

Citation: Journal of the American Veterinary Medical Association 263, 3; 10.2460/javma.24.09.0632

Figure 2
Figure 2

Local wound infiltration of LB into the subcutaneous perianal tissue was performed circumferentially around the incision site following closed anal sacculectomy in dogs. The local wound infiltration was performed either immediately before wound closure (A) or immediately after wound closure (B).

Citation: Journal of the American Veterinary Medical Association 263, 3; 10.2460/javma.24.09.0632

Statistical analysis

All analyses were performed by a biostatistician using SAS (version 9.4; SAS Institute Inc). A significance level of .05 was used. The assumption of normality for age and weight was evaluated via inspection of QQ- and PP-plots, histograms, and skewness. Both were normally distributed and summarized descriptively with mean, SD, and range. Wilson CIs were calculated for binomial proportions. Sex distributions were compared between dogs that received and did not receive LB by a Fisher exact test due to expected cell counts < 5, and laterality and hospital distributions were compared with χ2 tests. Continuous factors were compared between dogs that received and did not receive LB by Welch t tests. Univariable and multivariable logistic regressions were used to estimate ORs and test for the effects of risk factors on complications. Five risk factors were analyzed in univariable analyses, and all were included in the multivariable analysis, namely group, tumor size (categorized as > 2.5 or < 2.5 cm), laterality, body weight, and age. Additionally, unilateral and bilateral surgeries were analyzed separately for group effects. Log-likelihood P values and ORs and relative risks with profile-likelihood OR confidence limits were reported.

Results

Medical records of 405 dogs at 2 veterinary referral practices were retrospectively reviewed, and 397 dogs were enrolled in this study. Eight dogs were excluded from the study for the following reasons: anal sacculectomy performed to achieve a margin for a perianal mass (n = 4), revision surgeries (2), incomplete medical records (1), and anal sacculectomy performed during bilateral perineal hernia repair (1). There were 5 intact females (1%), 150 spayed females (38%), 23 intact males (6%), and 219 neutered males (55%). The most represented dog breeds included the following: mixed breed (n = 148), Labrador Retriever (23), Golden Retriever (18), Cavalier King Charles Spaniel (15), Beagle (15), German Shepherd Dog (14), and Dachshund (13). Sixty-four other breeds were represented, with < 10 dogs per breed. The mean (SD) body weight was 21.4 kg (12.8 kg), and the mean (SD) age was 9.3 years (2.8 years).

Two hundred sixty-one of the 397 dogs (65.7%) received LB (LB group) and 136 of 397 (34.3%) did not receive LB (non-LB group). There were no significant differences in distribution of dogs by sex (P = .890), laterality (P = .092), age (P = .552), weight (P = .793), or hospital (P = .711) between the groups.

Unilateral closed anal sacculectomy was performed in 292 of 397 dogs (74%). Bilateral closed anal sacculectomy was performed in 105 of 397 dogs (26%). The most common diagnoses prompting anal sacculectomy were AGASACA (266 of 397 [67%]) and anal sacculitis (103 of 397 [26%]; Table 2).

Table 2

Diagnoses leading to unilateral or bilateral closed anal sacculectomy in dogs. Different diagnoses were made in each anal sac in 6 bilateral cases.

Diagnosis No. (%) of unilateral cases No. (%) of bilateral cases
AGASACA 236/397 (59.4) 30/397 (7.6)
Anal sacculitis 37/397 (9.3) 66/397 (16.6)
Anal sac abscess 6/397 (1.5) 1/397 (0.25)
Melanoma 5/397 (1.3) 0/397 (0)
Perianal fistula 1/397 (0.25) 3/397 (0.76)
Squamous cell carcinoma 3/397 (0.76) 0/397 (0)
Trichoepithelioma 1/397 (0.25) 0/397 (0)
Leiomyoma 1/397 (0.25) 0/397 (0)
Perianal adenoma 1/397 (0.25) 0/397 (0)
Anal sacculitis + AGASACA 0/397 (0) 4/397 (1)
Anal sacculitis + leiomyoma 0/397 (0) 1/397 (0.25)
Anal sacculitis + perianal adenoma 0/397 (0) 1/397 (0.25)

AGASACA = Apocrine gland anal sac adenocarcinoma.

The overall short-term postoperative complication rate in the study was 24% (94 of 397; 95% CI, 20% to 28%), and the short-term postoperative complication rates for dogs in the LB and non-LB groups were 22% (57 of 261; 95% CI, 17% to 27%) and 27% (37 of 136; 95% CI, 17% to 27%), respectively (P = .236). The relative risk for overall short-term postoperative complications was 0.80 (95% CI, 0.56 to 1.16), indicating that, on the basis of these data, LB was not found to be associated with an increased risk of short-term postoperative complications, with the 95% CI ranging from a 44% decrease to a 16% increase in risk (eg, 24% would increase to 28% if a 16% increase were realized; Table 3).

Table 3

Short-term postoperative complication rates associated with use and nonuse of liposomal bupivacaine (LB) in closed anal sacculectomy cases in dogs.

Overall complications Fecal incontinence
LB group 57/261 (22%); 95% CI, 17%–27% 16/261 (6%); 95% CI, 4%–10%
Non-LB group 37/136 (27%); 95% CI, 20%–35% 15/136 (11%); 95% CI, 7%–17%
Relative risk 0.80 (95% CI, 0.56–1.16) 0.56 (95% CI, 0.28–1.10)
P value .236 .091

One hundred six postoperative complications potentially attributable to use of LB were diagnosed in 94 dogs and classified according to the Clavien-Dindo classification system.13 Twelve dogs each had 2 complications reported, and the remaining 82 dogs each had 1 complication reported. Forty-four complications were classified as grade 1, 22 complications as grade 2, 38 complications as grade 3, and 2 complications as grade 5. No complications were classified as grade 4. Complications that could not be reasonably attributed to LB usage were documented but excluded from statistical analysis. These complications included hypocalcemia in 5 of 397 dogs (1.3%), local recurrence in 3 of 397 dogs (0.76%), metastasis to sublumbar (medial iliac, sacral, and iliosacral) lymph nodes in 1 of 397 dogs (0.25%), rectal wall avulsion (a defect in approx 50% of the circumference between the colon and anus was reported) in 1 of 397 dogs (0.25%), Addisonian crisis in 1 of 397 dogs (0.25%), gastric dilatation and volvulus in 1 of 397 dogs (0.25%), aspiration pneumonia in 1 of 397 dogs (0.25%), hypoglycemia in 1 of 397 dogs (0.25%), acute kidney injury in 1 of 397 dogs (0.25%), and urethral tear in 1 of 397 dogs (0.25%). These complications were all classified as either grade 3 or 4 in the Clavien-Dindo classification system. The 2 dogs classified as grade 5 were euthanized because the clients elected not to proceed with treatment in the face of the postoperative complications. One dog (AGASACA) developed a surgical site infection, and the other dog (anal sac melanoma) developed spontaneous hemorrhage from the surgical site that required additional surgical intervention.

The overall short-term postoperative fecal incontinence rate was 8% (31 of 397; 95% CI, 6% to 11%), and the fecal incontinence rate in the LB and non-LB groups was 6% (16 of 261; 95% CI, 4% to 10%) and 11% (15 of 136; 95% CI, 4% to 10%), respectively (P = .091). The relative risk for fecal incontinence was 0.56 (95% CI, 0.28 to 1.10), indicating that LB was not associated with an increased risk of fecal incontinence following anal sacculectomy (Table 3), and the 95% CI ranged from a 72% decrease to a 10% increase in risk. The risk of complications was 1.9 times higher when the tumor size was > 2.5 cm compared to < 2.5 cm (univariable OR, 1.9; 95% CI, 1.0 to 3.6; P = .041 univariable; P = .038 multivariable; Table 4). The short-term postoperative complication rate for unilateral anal sacculectomies was 22% (63 of 292) compared to 30% (31 of 105) for bilateral anal sacculectomies (P = .116). When the LB and non-LB groups were compared for bilateral and unilateral anal sacculectomies separately, short-term postoperative complication rates for the LB versus non-LB group were 22% (43 of 199) versus 22% (20 of 93) for unilateral surgeries (P = .984) and 23% (14 of 62) versus 40% (17 of 43) for bilateral surgeries (P = .062).

Table 4

The impact of risk factors on postoperative complications in dogs treated with anal sacculectomy.

Factor Effect Univariable Multivariable
OR (95% CI) P value OR (95% CI) P value
Tumor size (mm) > 2.5 vs < 2.5 1.93 (1.03–3.61) .04 1.99 (1.04–3.78) .04
LB Yes vs no 0.75 (0.47–1.21) .24 0.81 (0.42–1.56) .51
Laterality Bilateral vs unilateral 1.52 (0.91–2.51) .11 1.48 (0.57–3.54) .41
Body weight Per kg 0.99 (0.97–1.01) .24 0.99 (0.86–1.14) .87
Age Per year 0.96 (0.89–1.04) .34 1 (0.97–1.03) 1.00

Discussion

Postoperative complications associated with closed canine anal sacculectomy have been reported in 17% to 20% of cases,4,5 although analysis of complications potentially associated with LB use were not performed in those studies. In the present study, the overall postoperative complication rate was 24% (95% CI, 20% to 27%), and infusion of LB during closure of closed anal sacculectomy wounds was not significantly associated with an increase in perioperative or short-term surgical site complications when compared to anal sacculectomy without LB, allowing us to accept our hypothesis.

Investigations into the association of LB use at hemorrhoidectomy surgical sites in humans has yielded similar results.14,15 While human hemorrhoidectomy and canine anal sacculectomy cannot be directly compared, the procedures have similar postoperative complication profiles due to the locoregional perianal anatomic landmarks found in both species. Furthermore, Solis-Pazmino et al15 reported that LB usage was associated with a decreased pain score at 72 postoperative hours, longer time to first opioid use, and decreased overall opioid use postoperatively in human hemorrhoidectomy cases. This retrospective study, however, did not aim to and was not capable of assessing LB’s efficacy as a local anesthetic in these cases, and further prospective research is needed to assess the efficacy of LB as a short-term local anesthetic in anal sacculectomy cases.

The overall complication rate in our study was higher than in previous studies evaluating anal sacculectomy complication rates, although previously reported studies evaluated more narrow populations of anal sacculectomy.4,5 Charlesworth5 reported a postoperative complication rate of 20% following bilateral anal sacculectomy procedures performed to treat chronic anal sacculitis. Among those cases, only 13% of dogs with postoperative complications required pharmacological or surgical intervention for resolution. Exclusion of all anal sacculectomies performed as treatment for a tumor may have lowered the complication rate due to the likelihood of smaller and less locally invasive anal sac tissue. Sterman et al4 reported a 17% postoperative complication rate following anal sacculectomy performed for treatment of AGASACA, with 32% of the complications requiring surgical intervention for resolution. However, postoperative sequelae (14%), such as self-limiting diarrhea, tenesmus, transient fecal incontinence, and others, were reported separately from their postoperative complications. In our study, 58.5% (62 of 106) of the total complications required pharmacological or surgical intervention for resolution.

In the present study, the risk of complications was 1.9 times higher when the tumor size was > 2.5 cm compared to < 2.5 cm. While the veterinary literature clearly shows a survival advantage for primary AGASACA tumors < 2.5 cm compared to those > 2.5 cm, it does not support tumor size as a risk factor for postoperative complications.6,12 In a 2023 study6 of anal sacculectomy for massive AGASACA tumors (> 5 cm), tumor size did not increase the risk for intraoperative or postoperative complications. Furthermore, no dog in the study had long-term fecal incontinence, tenesmus, or anal stenosis or stricture.6 It is unclear why tumor size was associated with increased risk of complications in our study when that has not been previously reported.6,12 Potentially, the difference could be attributed to how complications were reported and analyzed in previous studies when compared to ours. Our study combined primary complications and likely sequelae as complications, while previous studies reported and analyzed sequelae separately. This difference in methodology may have resulted in sequelae associated with increased dissection or dead space in large tumor cases being included as complications in our study’s analyses. Additionally, our study included all causes of anal sacculectomy, while Griffin et al6 reported only AGASACA cases, which may have contributed to these differences.

The LB regional infiltration methodology used in this study was similar to the method described by Lascelles et al8 for use in dogs undergoing stifle stabilization procedures. However, in contrast to the described use in stifle surgery in which the tissues of the joint capsule, fascial plane, and subcuticular tissue were all infused,8 infusion of LB was limited to the subcutaneous tissue due to the limited amount of other soft tissue layers in that anatomical region.

There were various limitations to the current study inherent to its retrospective nature. The CDC recommendation in human medicine is to have a 30-day surveillance period for surgical site infections following rectal surgery.16 However, veterinary postoperative recheck examinations are routinely performed between 10 and 14 postoperative days to coincide with suture removal. It is possible that some surgical site infections were missed if they occurred between 15 and 30 postoperative days. Second, even though all the cases in this study were closed anal sacculectomies, variation can exist among surgeons regarding dissection technique (sharp dissection with Metzenbaum scissors vs monopolar electrocautery vs a bipolar vessel-sealing device). That information was not consistently reported in all medical records. The rate of surgical site complications therefore may have been impacted on the basis of which surgical dissection technique was utilized. To our knowledge, the impact of the dissection technique on postoperative complications following closed anal sacculectomy has not been reported.

In conclusion, these retrospective results suggest that administration of LB was not significantly associated with an increase in short-term postoperative complication rates following anal sacculectomy in dogs. Prospective studies investigating the efficacy of LB administration during closed anal sacculectomy procedures are indicated.

Acknowledgments

Brayden Routh, DVM, created the artwork in Figure 1.

Disclosures

The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.

Funding

The authors have nothing to disclose.

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