A novel needle-free method of lidocaine administration during standing castration of Holstein bulls

Graphical Abstract

Summary Administration of the drug lidocaine can make castration less painful for bulls. Usually, it is injected into the animal using a needle and syringe before the procedure. This process can be time consuming and dangerous for veterinarians and animals alike. One alternative route of administration relies on pneumatic needle-free injection (NFI). This process may offer benefits over traditional injection, but it is unclear if it is as effective at delivering lidocaine and minimizing pain as traditional methods. Our group conducted an experiment to determine this and found that both techniques offer comparable benefits.

Highlights

• •Standing bovine castration is a painful procedure that is part of routine herd management.
• •The present study sought to compare the pain-relieving benefits of 2 methods of lidocaine administration.
• •Both traditional (through-the-needle) and NFI methods showed comparable responses after castration.

Abstract:

The American Veterinary Medical Association recognizes castration to be important for both human and animal safety. Lidocaine delivered through-the-needle has been shown to be effective at reducing cortisol response to castration, but this method has drawbacks for both animals and caretakers. As such, a study was conducted to examine the potential benefits of lidocaine delivery using a pneumatic needle-free device immediately before standing bovine castration. Twelve Holstein bulls weighing 400.7 ± 39.5 kg (mean ± standard deviation) were enrolled. Bulls were allocated to receive a local anesthetic block of 2% lidocaine for surgical castration by traditional needle injection or by needle-free injection. Outcomes were collected out to 48 h postcastration. Outcome variables included plasma cortisol concentrations, visual analog scale scores for pain, medial canthus temperatures as measured using infrared thermography, pressure mat changes, and chute defense scores. A time effect was observed for cortisol, visual analog scale scores, infrared thermography temperatures, and some pressure mat outcomes. No statistically significant differences between lidocaine delivery methods were observed, but further research is needed to build upon this small dataset.

Castration of male cattle (bulls) is part of routine herd maintenance in many parts of the globe. In the United States, approximately 88% of male beef cattle are ultimately castrated (Rault et al., 2011), which translates to 15 to 17 million individual procedures per year. Reasons for castration are myriad but include reduced aggressiveness (Goodrich and Stricklin, 1997) and mounting behavior as a result of decreased androgen production (Tarrant, 1981). Castration also controls unwanted breeding (Stafford and Mellor, 2005) and improves meat quality (Jones, 1995) in animals destined for human consumption. Physical castration, a method that is common in production settings (Coetzee, 2013), involves the infliction of irreparable damage to or surgical removal of testes. All physical means of castration have related side effects including the presentation of pain. Acute pain may most immediately manifest as agitated chute behavior (Thüer et al., 2007) with animals kicking, stamping feet, swishing tails (Fisher et al., 2001), or otherwise appearing restless and abnormally discomforted following physical castration (Ting et al., 2003). More chronic signs of pain can be protracted up to 120 h (Martin et al., 2022a) and include changes in ocular temperature, gait, and cortisol. In the case of surgical castration, wound healing can take more than 56 d (Marti et al., 2018). Despite the painful nature of castration, and the fact that veterinarians are oathbound to “[protect] … animal health and welfare” (https://www.avma.org/resources-tools/avma-policies/veterinarians-oath), only a small minority of surveyed US bovine veterinarians routinely administer local anesthesia (e.g., the amino amide lidocaine) during castration (Johnstone et al., 2021). This is in spite of evidence suggesting a tendency for preemptive lidocaine administration to lower peak plasma cortisol concentrations after castration (Webster et al., 2013). Suggested reasons for clinician hesitancy include excessive cost and time required to administer local anesthesia, which can add up to 10 min to each procedure (Coetzee et al., 2010). If a more efficient method of lidocaine administration with a faster onset of activity was identified, this may increase on-farm usage of local anesthetic protocols.

The premise of needle-free injection (NFI) has existed for decades (Lockhart, 1943) with billions of NFI having been given as part of widespread human vaccination campaigns (Voelker, 1999). Benefits of NFI may include increased safety for clinicians and patients from bloodborne illness during drug administration (Reinbold et al., 2010), and depending on the model, injectors are capable of delivering either liquid (du Châtelet et al., 1997) or powdered (Chen et al., 2000) drugs. Relevant to the present experiment is the potential for NFI to deliver drug quickly to many patients versus using traditional needles and syringes (Giudice and Campbell, 2006). This feature may make it particularly attractive to veterinarians and producers in large animal production settings.

In veterinary medicine, NFI technology has been shown to be capable of delivering vaccines to swine (Houser et al., 2004), cattle (Hollis et al., 2005), horses (Phillips et al., 2011), and chickens (Ogunremi et al., 2013). In pigs, the technology has shown promise as a means to deliver lidocaine immediately before castration (Sutherland et al., 2017), but this concept has not been tested in other species. Based on these studies, NFI technology may offer an alternative to traditional needle-based pain management techniques for cattle.

The objective of the present study was to evaluate a needle-free route of lidocaine administration during standing castration of Holstein bulls. Our group hypothesized that this novel protocol would deliver the pain-limiting benefits of local anesthesia as effectively as traditional methods of delivery. Data generated may help inform future studies of NFI technology as well as management decisions related to pain mitigation. The experiment was not designed to evaluate effects of lidocaine administration itself. Rather, the goal was to compare a relatively new route of administration (NFI) to current methods of lidocaine injection using a needle and syringe.

The experimental protocol for this project was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at Kansas State University (IACUC #4394.18). A rescue analgesia protocol was in place, in accordance with IACUC guidance and attending veterinarian consult, for calves deemed to be experiencing severe pain. Indicators of severe pain included excessive swelling, inappetence, dull appearance, and reluctance to move from a standstill or recumbency. In the event that an animal met the criteria for rescue analgesia, it was provided in the form of oral meloxicam (Zydus, Pennington, NJ) at a dose of 1 mg/kg or transdermal flunixin (Banamine Transdermal, Merck Animal Health, Madison, NJ) at a dose of 3.3 mg/kg.

Twelve postpubertal Holstein bulls of 400.7 ± 39.5 kg (mean ± SD) BW were enrolled in the study, which took place at the College of Veterinary Medicine at Kansas State University in October 2021. Castration of these animals was scheduled as part of an unrelated experiment and was not conducted exclusively for the present study. Each experimental group (NFI and traditional) was allocated 6 (n = 6) animals for this trial. Bulls were kept in group housing with access to shelter and ad libitum hay and water. A grain-based diet was formulated at 3.5% BW and divided into 2 daily feedings as per normal procedures at the study site. All animals were approximately 54 wk of age and had fully descended testicles and scrotums of normal gross morphology. Scrotal circumference averaged 334.4 ± 20.5 mm at study outset, and no animals were excluded for failure to present descended testicles.

Study bulls were randomly divided into treatment groups using the RAND function in Microsoft Excel (Microsoft Excel 2016, Microsoft Corporation, Redmond, WA). Bulls were restrained in a squeeze chute during lidocaine administration and castration. Six bulls were allocated to receive 2% lidocaine via traditional needle injection by injecting 4 mL into each spermatic cord and 2 mL into the median raphe of the scrotum. The remaining 6 bulls received 2% lidocaine via a NFI device calibrated to 586 kPa per the manufacturer's recommendation (Pulse NeedleFree Systems, model 250, Lenexa, KS). For the NFI, two 2-mL injections were administered into each spermatic cord followed by a 2-mL injection into the median raphe of the scrotum. Regardless of treatment group, a total of 10 min elapsed between lidocaine administration and the castration incision. Scrotums were cleaned using a mix of sterile water and chlorhexidine surgical scrub (Chlorhexidine 4%, VetOne, Boise, ID) with cotton gauze soaked in 70% isopropyl alcohol (Vedco, St. Joseph, MO). Insensitivity was confirmed by pinching the scrotum with hemostats before incising. The distal half of the scrotum was then incised using a disposable scalpel blade (Kendall Scalpel 11, Covidien LLC, Mansfield, MA). Testes and spermatic cord were exteriorized by blunt dissection, and testicles were removed by stripping and twisting the spermatic cord. All animals also received meloxicam at 1 mg/kg BW orally before the lidocaine injections to control inflammatory pain (Coetzee et al., 2012). Postprocedural care was provided as per an IACUC-approved animal monitoring plan.

To quantify changes in serum cortisol concentrations, blood was harvested from the external jugular veins into vacuum tubes (Vacutainer, BD Diagnostics, Franklin Lakes, NJ). Animals were restrained in a squeeze chute with a rope halter and between 10 and 15 mL of whole blood was drawn by venipuncture at each time point. Time points for blood collection were 24 h before, 10 min before, and 0.5, 1, 2, 4, 8, 24, and 48 h after castration. Tubes were inverted 3 times and then placed on ice for transport to the laboratory. Tubes were then centrifuged (CL2 Centrifuge, Thermo Electron Corp., Waltham, MA) for 10 min at 1,500 × g and 4°C to facilitate plasma collection via transfer pipette. Plasma was stored in cryovials (T310 Self Standing, Simport Scientific, Saint-Mathieu-de-Beloeil, QC, Canada) at −80°C until analysis.

Cortisol concentrations were measured using a commercially available assay (125 RIA Kit, MP Biomedicals, Solon, OH) as per the manufacturer's directions. A gamma-counter (Wizard2, PerkinElmer, Waltham, MA) was used to measure samples in duplicate for 60 s each. Raw data were then uploaded to the appropriate software (MyAssays, v7.0.211.1238, Brighton, UK). Samples found to have a coefficient of variation greater than 18% were reanalyzed. The assay had a detection range of 0.10 to 30 ng/mL. The coefficient of variation for the intraassay variability was 21.0% and the interassay variability was calculated to be 14.0%.

Infrared thermography (IRT) data were collected using a Fluke imager (Fluke TiX580, Fluke Corporation, Everett, WA). Images of the medial canthus of the left eye were taken from a distance of 50 cm using methods modified from a previous experiment (Kleinhenz et al., 2017). Time points for imagery were the same as for blood collection. Subsequent analysis used appropriate software (SmartView 4.3, Fluke Thermography, Plymouth, MN) to generate descriptive statistics of the imagery. This software was used to quantify the maximum, mean, and minimum temperature recorded within each image.

To measure changes in gait, a commercially available pressure mat system was used (Walkway, Tekscan Inc., Norwood, MA). Before use, the pressure mat was calibrated as per manufacturer's instructions using an object of known mass (20.4 kg). Strides were synchronized among calves using appropriate software (Walkway 7.7, Tekscan Inc.) and outcome measures included gait distance (cm), gait velocity (cm/s), stance time (s), individual limb stride length (cm), individual limb force (kg), and individual limb force time interval (FTI, kg·s). Pressure mat time points were 24 h before, and 2, 4, 8, 24, and 48 h after castration. Changes in these outcomes relative to their baseline (precastration) values were analyzed.

A visual analog scale (VAS) served as a real-time indicator of pain. Methods were adapted from those used previously (Martin et al., 2020). Briefly, the scale used a 100-mm line spanning the descriptors “no pain” and “severe pain” at opposite ends. According to the VAS, painful animals were expected to exhibit dull demeanors, frequent tail swishes (>3/min), reluctance to move, thoracic and pelvic limb abduction, spinal kyphosis, and ventrally angled pinnae (Rault et al., 2011). Conversely, a lack of pain was expected to be characterized by alertness, motionless tails, a relatively straight spine, and head carriage above spine level. Two trained and blinded evaluators examined animals and placed a mark on the line to indicate the severity of pain observed. These marks were later measured by third parties blinded to treatment. Mean VAS scores of the evaluators were combined for analysis. Scoring time points were 30 min before, and 2, 4, 8, 24, and 48 h after castration.

Chute defense behavior was video recorded (Sony Handycam HDR-CX405, Sony USA Inc., New York, NY) as animals were castrated while restrained in a squeeze chute. A blinded, trained evaluator used an adapted 5-point scale (Grandin, 1993) to assess behavior and is summarized as (1) calm with no movement, (2) restless or shifting or both, (3) squirming and occasionally shaking chute, (4) continuous vigorous movement and chute shaking, and (5) rearing, body twisting, and violent struggling.

Analysis relied on statistical software (JMP Pro 15.1.0, SAS Institute Inc., Cary, NC) to test for significant differences between treatments. Response outcomes included plasma cortisol concentrations, VAS scores, ocular IRT measurements, pressure mat analysis outcomes, and chute defense behavior. Responses were analyzed using a mixed model with the individual animal considered the experimental unit. Treatment was assigned as the random effect. Time and treatment by time interaction were considered fixed effects. Concentrations of serum cortisol were log-transformed for normality before analysis. Post hoc tests were conducted using Tukey-Kramer adjustment. Significance was set a priori at P ≤ 0.05. Results are summarized in Table 1.

Table 1.

Summary table of overall mean response variables for calves (n = 6 per treatment) receiving lidocaine in either a traditional way or using a needle-free injection (NFI) device

Response1	Overall treatment mean (95% CI)		P-value
	NFI	Traditional	Treatment	Time	Treatment × time
Cortisol (ng/mL)	1.66 (1.31–2.01)	1.83 (1.49–2.17)	0.4547	<0.0001	0.518
VAS (mm)	25.90 (20.53–31.28)	24.07 (18.70–29.44)	0.6027	<0.0001	0.7247
Mean IRT (°C)	33.44 (32.97–33.90)	33.57 (33.10–34.04)	0.6679	<0.0001	0.3832
Maximum IRT (°C)	37.14 (36.81–37.47)	37.16 (36.83–37.49)	0.9245	<0.0001	0.9665
Minimum IRT (°C)	26.75 (25.86–27.64)	27.03 (26.14–27.92)	0.6324	<0.0001	0.2804
Gait distance (cm)	168.21 (159.44–176.97)	159.19 (150.42–167.95)	0.136	0.3649	0.0541
Gait velocity (cm/s)	91.8 (82.69–100.9)	102.58 (93.47–111.68)	0.0917	0.0048	0.2923
Stance time (s)	1.11 (0.99–1.24)	1 (0.87–1.12)	0.1686	0.5583	0.4147
Stride length (cm)	137.32 (133.15–141.50)	141.88 (137.7–146.05)	0.1162	0.021	0.85
Limb force (kg)	165.66 (153.17–178.15)	161.54 (149.05–174.03)	0.615	0.00051	0.2614
FTI (kg·s)	109.49 (96.23–122.75)	101.84 (88.58–115.1)	0.3849	0.0316	0.8779
Chute defense	2 (1.33–2.67)	1.67 (1–2.33)	0.4379	—	—

¹VAS = visual analog scale; IRT = infrared thermography; FTI = force time interval.

Cortisol values were found to elevate immediately after castration and remain above baseline for several hours (Figure 1). The effect of time on cortisol concentration was significant (P < 0.0001). Cortisol appeared to peak approximately 1 h after the castration procedure, whereas the nadir was measured 24 h beforehand. After approximately 8 h after castration cortisol values returned to near-original levels, but at no point during the sampling regimen (up to 48 h postcastration) did treatment appear to have a significant effect on cortisol concentrations (P > 0.05).

Figure 1.

Cortisol concentration over time for calves (n = 6 per treatment) receiving lidocaine in either a traditional way or using a needle-free injection (NFI) device. Error bars are SE.

The VAS scores followed a pattern similar to that noted in cortisol response. Again, the effect of time on outcomes was significant (P < 0.0001). The lowest mean VAS scores were measured 30 min before castration. Mean VAS scores increased until approximately 4 h after castration and then decreased through the remaining 48-h sampling period. There was no significant effect of treatment on VAS scores over the course of the experiment (P > 0.05).

Ocular IRT data showed that only time had a significant (P < 0.0001) effect on medial canthus temperatures. When plotted over time, ocular temperatures peaked 24 h before castration, exhibited a nadir at the time of and immediately following the procedure, and rebounded at 8 h postcastration. Treatment did not have a significant effect on these values over time (P > 0.05).

Treatment in general was not found to have a significant effect on gait outcomes during postcastration sampling. Specifically, treatment had no significant effect on changes in gait distance over time when compared with baseline values (P > 0.05). In addition, the effect of time on gait distance was not found to be significant. Likewise, when changes in gait velocity relative to baseline were considered, treatment was not found to have a significant effect. Time, however, had a significant effect (P = 0.0048) with animals in both treatment groups exhibiting lower velocities following castration. Treatment was not found to affect gait velocity over time. Neither treatment nor time had significant effects on limb stance times. Similarly, no significant treatment effect was measured for stride length, limb force, or FTI during the sampling regimen.

Finally, treatment did not appear to have a significant effect (P > 0.05) on chute defense behavior scores. The mean chute defense behavior score for traditional anesthesia delivery was 1.67 ± 0.30 with a 95% confidence interval of 1.00 to 2.33. For NFI, the mean chute defense behavior score was 2.00 ± 0.30 with a 95% confidence interval of 1.33 to 2.67. These values indicate that in neither treatment group did animals exhibit squirming or shaking of the chute. Additionally, animals did not exhibit continuous vigorous movement or rearing, twisting, or violent struggling in the chute.

By comparing NFI to traditional anesthesia delivery, this experiment sought to answer an important question pertaining to animal welfare in cattle. Specifically, data suggest that the way by which NFI delivers local anesthesia to the scrotum of bulls before castration was not different to traditional methods. Data presented here suggest analogous behavioral responses between NFI and traditional groups, as quantified by VAS scores, and are in line with what was previously shown in pigs (Sutherland et al., 2017). Likewise, IRT data presented here are in agreement with past work that showed low medial canthus temperatures immediately after a painful procedure (cautery dehorning) followed by temperature rebound (Kleinhenz et al., 2017). Across both groups, measured cortisol concentration displayed a trend of quick elevation followed by a slow escalation, which is also supported by published literature (Earley and Crowe, 2002). Previous work has shown a decreased stride length in response to castration (Currah et al., 2009), which was also noted in the present study. Similarly, previous research has shown an increase in force applied to the front feet in cattle castrated (Kleinhenz et al., 2018; Martin et al., 2022b) and these changes were also observed in this study. In general, evidence from the present work suggests that NFI is just as effective at delivering the benefits of local anesthesia as traditional methods.

The present study is the first of its kind and can be further elucidated. Future work should build on these findings by incorporating a treatment group of bulls that receive no local anesthetic before castration to better quantify the magnitude of pain relief provided by NFI-delivered anesthesia. Additionally, future experiments should be designed to compare the time required for NFI versus traditional anesthesia injection to take effect. If time savings are found to be meaningful, subsequent adoption of NFI technology could result in higher rates of anesthesia compliance and corresponding animal welfare improvements.