Nerve blocks applied to the distal aspect of a limb (distal to the carpus or tarsocrural joint) of horses usually cause desensitization of the area of innervation within 5 minutes. However, it takes at least 20 minutes for nerve blocks that are performed more proximally in a limb to provide desensitization sufficient to cause observable improvement in the gait.2–5 A decrease in the time required to perform some lameness examinations might be achieved by increasing the rapidity of onset of regional nerve blocks.
Chloroprocaine is an ester local anesthetic that is quickly metabolized to para-aminobenzoic acid, which has the potential to cause allergic reactions. For this reason, clinical use of ester local anesthetics has largely been replaced by the use of amide local anesthetics, which have low potential to cause allergic reactions. However, the ester local anesthetics procaine and chloroprocaine are still commonly used in human medicine, primarily for obstetric purposes. Because chloroprocaine has a rapid onset, its use in diagnostic analgesia might be advantageous when performing median or ulnar regional nerve blocks in horses. To our knowledge, no reports exist of the use of chloroprocaine for diagnostic analgesia in horses. The objective of the study reported here was to evaluate onset of analgesia with 3% chloroprocaine hydrochloride and 2% mepivacaine hydrochloride when performing median and ulnar nerve blocks in horses with naturally occurring lameness. We hypothesized that use of 3% chloroprocaine for median and ulnar nerve blocks would result in a more rapid onset but shorter duration of analgesia than when these nerve blocks were performed with 2% mepivacaine.
Materials and Methods
Horses
Six horses with naturally occurring lameness were obtained from the teaching herd of the Auburn University College of Veterinary Medicine for the study. The horses were all geldings and consisted of 5 Quarter Horses and 1 Thoroughbred. Mean ± SD body weight was 532.95 ± 42 kg (range, 506.8 to 613.6 kg), and mean age was 13.5 ± 3.8 years (range, 9 to 19 years). All horses were lame in both forelimbs as determined by results of previous diagnostic analgesia, but they consistently had a subjectively more observable lameness in 1 forelimb when trotting on a hard surface in a straight line before application of a nerve block. The study was approved by the Animal Care and Use Committee of Auburn University (No. 2018-3247).
Experimental procedures
Horses were randomly assigned by coin toss to initially receive 1 of 2 treatments first in a crossover design. For 1 treatment, median and ulnar nerve blocks were performed by administration of 2% mepivacaine hydrochloride.a For the other treatment, median and ulnar nerve blocks were performed by administration of 3% chloroprocaine hydrochloride.b Three horses initially received 2% mepivacaine, and the other 3 horses initially received 3% chloroprocaine. For both treatments, lameness was objectively evaluated immediately before application of the regional nerve block (time 0) and 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 75, 90, 105, and 120 minutes after treatment administration. A 7-day washout period was then provided, after which horses received the alternate treatment and lameness evaluations were repeated.
Nerve block technique
Median and ulnar nerve blocks were performed together because blocking these nerves individually for assessment of gait is of little benefit for determining the location of pain.6,7 The ulnar nerve was anesthetized first by inserting a 23-gauge, 1-inch needle to its hub in the groove between the ulnaris lateralis and flexor carpi ulnaris muscles at a site 10 cm proximal to the accessory carpal bone. An aliquot (10 mL) of the local anesthetic was administered during retraction of the needle to a subfascial position. Next, the median nerve was anesthetized on the caudomedial aspect of the radius just distal to the cubital (elbow) joint at the site where the ventral edge of the posterior superficial pectoral muscle inserted on the radius. At this site, a 23-gauge, 1-inch needle was inserted and directed caudolaterally through the fascia close to the caudomedial surface of the radius to a depth of 1 to 2.5 cm. An aliquot (25 mL) of the local anesthetic was administered.
Measurement of forelimb lameness
Forelimb lameness was measured by use of a wireless inertial sensor-based motion analysis systemc as horses trotted on an asphalt surface in a straight line for a minimum of 25 strides. The lameness measurement system detected and quantified forelimb lameness by recording vertical head acceleration. Vertical head acceleration was converted to relative vertical position, and mean and SD values for MaxHDiff and MinHDiff were determined for all strides. The MaxHDiff was calculated as the maximum head height after left forelimb pushoff minus the maximum head height after right forelimb pushoff, and MinHDiff was calculated as the minimum head height during right forelimb stance minus the minimum head height during left forelimb stance. Localization of lameness to the right or left thoracic limb within the stride was determined by the association of head movement with the angular velocity signal of a gyroscope placed on the right thoracic limb, which was used as a stride-timing index marker.8,9 Positive values for MinHDiff indicated lameness of the right forelimb, and negative values indicated lameness of the left forelimb. Total vertical head movement asymmetry, which indicated the amplitude of forelimb lameness, was assessed as VS. The VS was defined as the square root of the sum of MaxHDiff2 and MinHDiff2. The approximate threshold for evidence of forelimb lameness as determined by use of VS was 8.5 mm.
Statistical analysis
Data are reported as mean ± SD. Values for VS were determined for all lameness evaluations. When lameness changed from one forelimb to the contralateral forelimb (MinHDiff changed from positive to negative or vice versa), VS was converted to a negative value. Residual plots of the VS data were evaluated to confirm a normal distribution. The VS data were modeled by use of repeated-measures analysis.d Correlated data were accounted for by use of the following linear equation10–12:
where y represents the vector of observations, x represents the treatment design matrix (treatment with 2% mepivacaine or 3% chloroprocaine and lameness evaluations at the various time points), β represents the vector of fixed treatment effects, z represents the random effects design matrix (horse),10–12 μ represents the vector of random block effects, and e represents the vector of experimental error. To account for nonindependence of observations within horses, 5 correlation structures were tested (compound symmetric, first-order autoregressive, Toeplitz, unstructured, and variance components).10,11 Models were compared by use of Akaike information criterion values.10–12 The autoregressive correlation structure was the model that provided the best fit for the VS data, as determined on the basis of Akaike information criterion values. The Kenward-Roger correction was used for all models.10–12 The P values for multiple comparisons were calculated by use of contrast statements; values of P ≤ 0.05 were considered significant.
Results
All horses had a change in the side of forelimb lameness at some point after the nerve block, which indicated resolution of lameness in the treated forelimb and a change in lameness in the contralateral forelimb. This resolution in lameness occurred more rapidly with 3% chloroprocaine than with 2% mepivacaine (Figure 1). Mean ± SD time to at least a 70% reduction of initial VS was 11 ± 6 minutes and 28 ± 27 minutes for 3% chloroprocaine and 2% mepivacaine, respectively. Mean time for VS to decrease to < 8.5 mm was 9 ± 6 minutes and 28 ± 26 minutes for 3% chloroprocaine and 2% mepivacaine, respectively. Duration of lameness resolution (at least a 70% reduction in VS) was not significantly different between nerve blocks with 3% chloroprocaine (99 ± 23 minutes) and 2% mepivacaine (90 ± 23 minutes). Mean duration of lameness reduction with a VS < 8.5 mm was 99 ± 23 minutes and 86 ± 23 minutes for 3% chloroprocaine and 2% mepivacaine, respectively. Also, nerve blocks performed with 3% chloroprocaine induced a significantly greater reduction in forelimb lameness, compared with that induced with 2% mepivacaine, at 20 (P < 0.001), 25 (P = 0.016), 30 (P = 0.005), and 40 (P = 0.011) minutes after injection.
Mean ± SD values for VS of 6 horses with naturally occurring lameness of a forelimb before (time 0) and at various points after simultaneous performance of median and ulnar nerve blocks with 3% chloroprocaine hydrochloride (solid line) or 2% mepivacaine hydrochloride (dotted line). There was a 7-day washout period between treatments. Lameness was recorded with a wireless inertial sensor-based motion analysis system. Negative values indicate that the lameness changed from the forelimb that received the nerve block to the contralateral forelimb. *Within a time point, value differs significantly (P ≤ 0.05) from the value for 3% chloroprocaine.
Citation: American Journal of Veterinary Research 81, 1; 10.2460/ajvr.81.1.13
Reduction in VS did not differ significantly (P = 0.741) between 3% chloroprocaine and 2% mepivacaine from 75 to 120 minutes after injection. The VS of vertical head movement differed significantly (P = 0.043) over time because of the decline of anesthetic effects during lameness evaluations from 75 to 120 minutes after injection (Figure 1).
Discussion
In the present study, median and ulnar nerve blocks performed with 3% chloroprocaine induced a more rapid and consistent amelioration of naturally occurring lameness in horses, compared with results for 2% mepivacaine. However, there was a similar duration of effect for both treatments. Chloroprocaine is the fastest-acting local anesthetic used in people.13 The rapid onset of effects for chloroprocaine is not related to its pKa (approx 9), which indicates that little of the compound's nonionized (fat-soluble) form is available for uptake by the neurilemma when injected into tissues with a pH of 7.4. Chloroprocaine most likely has a more rapid onset because it can be used in a higher concentration owing to its low systemic toxic effects, compared with those of other local anesthetics.14 A higher concentration of chloroprocaine deposited in the perineural space means that there is a greater number of molecules available for diffusion across the neurilemma for more rapid onset of action than achieved with local anesthetics administered at a lower concentration.14 It is possible that 3% mepivacaine would have had the same rapid onset of effects as 3% chloroprocaine, but that concentration of mepivacaine was not readily available for veterinary use. It is primarily used for human dentistry and is packaged in cartridges rather than multiple-dose vials; we could find no reports of alternative concentrations or packaging.
A study15 conducted to examine the physiochemical properties of commonly administered local anesthetics showed that the ester-linked local anesthetics are more potent than their amide-linked counterparts, in particular that 2% chloroprocaine is more potent than 2% mepivacaine. The total dose (volume X concentration) of local anesthetic determines the onset, quality, and duration of a nerve block.13 In the study reported here, we compared the analgesic effects of 2% mepivacaine with those of 3% chloroprocaine; therefore, our results cannot be interpreted to indicate that chloroprocaine was a more potent local anesthetic than mepivacaine in horses. Rapidity of onset is dependent on several factors in addition to dose, including the innate properties of the local anesthetic, proximity of local anesthetic to the nerve, size of the nerve, pKa of the local anesthetic, and characteristics of the tissues surrounding the nerve. Because onset of action of a local anesthetic is related to its concentration as well as its physiochemical properties,14 results of the present study also cannot be interpreted to indicate that onset of action for mepivacaine was slower than that of chloroprocaine. However, our results indicated that 3% chloroprocaine was more potent and had a more predictable onset than did 2% mepivacaine for median and ulnar nerve blocks.
The objective of the study reported here was to identify a local anesthetic that would provide a more rapid onset of analgesia than others for ulnar nerve blocks when used during an examination to localize lameness in horses. In this respect, 3% chloroprocaine appeared to be superior to 2% mepivacaine. An unexpected finding was that the duration of effect with 3% chloroprocaine was longer than anticipated, although it was not significantly different from the duration of effect with 2% mepivacaine. For humans, chloroprocaine is listed as a short-duration local anesthetic with a duration of analgesia of approximately 30 minutes, whereas mepivacaine is listed as an intermediate-duration local anesthetic with a duration of analgesia of approximately 120 minutes.14 Duration of desensitization caused by a local anesthetic is markedly influenced by vascular effects of the drug. Most local anesthetics, when administered at clinically effective doses, cause some degree of vasodilation. In general, the greater the degree of vasodilation is, the shorter the duration of analgesia.14 The vasculature near the site of administration therefore likely plays a role in the duration of effect of a local anesthetic.14 The nature of the vasculature at the site of injection in combination with the vascular effects of chloroprocaine could have been a possible explanation for the unexpected prolonged duration of lameness resolution in horses treated with 3% chloroprocaine in the present study.
Chloroprocaine, similar to other amino-ester local anesthetics, has a short shelf-life16 and is approximately twice the price of 2% mepivacaine. Economics may preclude use or chloroprocaine by some equine practitioners.
Acknowledgments
No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.
The authors thank Taylor Gwynn, Cassie Claunch, and Jessica Brown for technical assistance with lameness evaluation of study subjects.
ABBREVIATIONS
| MaxHDiff | Maximum difference in relative vertical height of the head between right and left halves of the stride |
| MinHDiff | Minimum difference in relative vertical height of the head between right and left halves of the stride |
| VS | Vector sum |
Footnotes
Carbocaine-V, Pfizer Inc, New York, NY.
Nesacaine-MPF, Fresenius Kabi LLC, Lake Zurich, Ill.
The Q, with lameness locator, Equinosis LLC, Columbia, Mo.
PROC MIXED, SAS, version 9.1, SAS Institue Inc, Cary, NC.
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