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Question Posted May 3, 2006
I am posting this for someone else, looking for suggestions for
analgesia/treatment of this horse... if there are specific questions I can
find the answer, but hopefully this covers the important bits
4 wk ago, a 11 y standardbred stallion was kicked during breeding, sustaining an injury to the right stifle. He was kept at the farm for the next 3 weeks, non-weight bearing lame, with stall rest and phenylbutazone.
1 wk ago, he was referred to a surgeon for evaluation, as the condition was not improving. He was taken to surgery for evaluation of the joint, and it was discovered that the medial femoral condyle had an irreparable comminuted fracture, and the pieces of the bone were removed. The meniscus was also torn and damaged, and the loose bits were removed at surgery. Evaluation of the tibia at this point demonstrated a marked lack of cartilage on the articular surface. Also, the joint was septic.
He was recovered in a pool, but when fully awake, would not tolerate the sling well. Post operative analgesia was provided with an epidural catheter, through which 50 mg morphine (15 mg/mL) and 80 mg xylazine were infused q. 6 h. the morphine was increased to 100 mg 2 days later due to perceived pain. He also received phenylbutazone, and was started on lidocaine (50 ug/kg/min) and ketamine (0.4 mg/kg/h increasing to 0.8) constant rate infusions.
He is also receiving k-penicillin and gentocin systemically, and amikacin 3 g/day via an intra-articular catheter. Cultures are still pending from the initial joint.
5 days after arrival, the epidural catheter stopped flushing well, and was removed. At that point, the horse was started on a morphine CRI after IM morphine loading dose (sorry, not sure of the rate). ketamine CRI was increased to 1.2 mg/kg/h, and other medications were continued as above.
When the joint is blocked (carbocaine), the pain is moderately better, but he is still reluctant to bear any weight on that stifle; lifting the contralateral limb will cause him to stand on tiptoe in the affected leg.
The horse still seems to be in a fair amount of pain, perhaps more so, since the d/c of the epidural catheter. my suggestions were to consider adding lidocaine in with the amikacin for a continuous intraarticular block and to reculture the joint and replace the epidural catheter.
They are reluctant to place the horse in a sling for support, because he tolerated the last sling so poorly (wouldn't bear weight on any limb).
Questions for the list, in addition to 'anything else you can think of' are:
What is an optimal total epidural volume to inject for analgesia of the hind limb, using a caudally placed epidural catheter, threaded up to the caudal sacrum?
Could intra-articular administration of amikacin cause inflammation/pain?
Benjamin M. Brainard
Response 1
About the volume of the epidural I think the important question is what drugs will you be giving. When I give only morphine I use 0.04ml/kg for total volume (around 20mls for a 500kg horse). I don't think volume makes such a big difference when it comes to morphine as it does for local anesthetics. I use that volume for caudal epidural with morphine, I'm not sure how much to reduce if you feed the catheter.
Have you considered morphine intra-articular?
I don't know about the amikacin sorry.
Manuel Martin Flores
Response 2
I recently treated a horse with intractable pain (even with epidural morphine, CRI's of butorphanol, lidocaine, detomidine, etc) with gabapentin. We used ~2.5 mg/kg PO BID/TID
Within 8 hours the horse was much more comfortable. This is an n=1, but didn't seem to cause any harm and in my opinion made the horse much more comfortable. It is reasonable that after 4 weeks, you might have a neuropathic component to the problem??? Weaned off with decreasing frequency when underlying problem resolved.
Lysa Pam Posner
Response 3
If intra-articular local anesthetics are not an option, it might be worth trying a lidoderm patch over the affected joint.
Pete Hellyer
Response 4
I think epidural volume is very important. Sufficient dura must be exposed to the drug for effective diffusion. My clinical experience suggests that at least 30 ml (when administered from caudal injection site) is needed to get reasonable control.
If the sufficient force was applied to result in meniscal injury, sufficient force may have been applied to seriously injury extraarticular soft tissue supporting structures such as collateral ligaments, patellar ligaments. Moreover, cruciate (cranial and/or caudal ligaments may have also been affected. If the area of trauma is large enough it is plausible that some nerve injury (either directly or indirectly) has occurred.
I often include lidocaine or bupivacaine with amikacin for single injections of joints, and have seen no untoward effects. The local anesthetics are mild to moderate antiinflammatory (and potentially immune suppressant) agents.
In any long standing pain state, central sensitization can exacerbate the patient's pain experience. NSAID and opiates are important tools, here, as are the adjunct anticonvulsant antihyperalgesics such as gabapentin, phenytoin. More than one NMDA receptor sub-type may be in play in this situation, and ketamine may not be the best blocker. Amantadine may be a possibility (I have no experience with this drug in horses) as may methadone.
Each patient's pain experience is unique. Finding the right effective combination of drugs and other therapeutic modalities and may require some experimentation, luck, expertise and innovativeness.
What is the long term outlook for sufficient joint stability in this animal for survival?
Michael Tomasic
Response 5
I agree that sufficient dura needs to be exposed to the administered agent, but there's also evidence that the cranial dispersion of hydrosoluble drugs such as morphine are more dependent on dose than volume. Since absorption is very low hydrosoluble drugs will progress cranially due to a concentration gradient. The opposite happens with liposoluble agents (such as fentanyl for example) in which cranial dispersion can be limited by absorption making volume a more important factor Natalini et al had shown thoracic increases in electrical threshold stimulation in horses hours after epidurally administered morphine at 0.04ml/kg if my memory doesn't fail (sorry I don't have the reference handy)
Manuel Martin Flores
Response 6
Thank you everyone for your suggestions. I agree with Dr. Tomasic, in that I think long-term prognosis for this joint and horse is poor. They decided to place him in the Anderson sling, to give a little more support, as he was beginning to develop a varus deformity in the opposite leg. I think they are also replacing the epidural catheter-- i wonder if they might consider methadone by that route-- and are going to start him on gabapentin as well. Apparently, it takes a long time to give 3 g. of amikacin into a joint (they have a specific closed-circuit pump), and so the additional volume of lidocaine or morphine would affect the dose; but we might find some 20% lidocaine and the 5% morphine, which may make that appropriate.
Thanks for your input, and I will let you know the outcome.
Benjamin M. Brainard
Response 7
I understand the dogma. I also have my clinical experience. Experience tells me I have a better chance of desired effect with sufficient volume.
Michael Tomasic
Response 8
I read Dr Hellyer's post about the Lidoderm patch. Is there research going on to the effectiveness on this product over joints? I am in the small animal field and have not found any solid information about using the patches for arthritic dogs. Most anesthesiologist that I have asked about this seem to believe it does not penetrate deeper than the skin. Does anyone have good clinical or research info on this?
Douglas Stramel
Response 9
Dr Lori Bidwell when at Michigan State did some research in horses looking at efficacy and also drug excretion in urine and plasma levels - she presented an abstract but I haven't seen the full paper yet. Hopefully she or one of her colleagues will chip in
Sheilah Robertson
Response 10
In response to Dr. Tramels's question there does not appear to be much literature out there yet specific to lidocaine patches in animals. The following abstract refers to the use of the patches in dogs.
Pete Hellyer
Title: Pharmacokinetics of a lidocaine patch 5% in dogs
Author(s): Weiland L, Croubels S, Baert K, Polis I, De Backer P, Gasthuys F
Source: JOURNAL OF VETERINARY MEDICINE SERIES A-PHYSIOLOGY
PATHOLOGY CLINICAL MEDICINE 53 (1): 34-39 FEB 2006
Document Type: Article
Language: English
Cited References: 34 Times Cited: 0
Abstract: Lidocaine is increasingly used in transdermal drug delivery systems for different pain conditions in human medicine whereby several pharmacokinetic studies have demonstrated minimal systemic absorption in men. In the present study, the pharmacokinetics of a lidocaine patch 5% was studied in six dogs. In the first experiment, one single lidocaine patch was applied for 12 h to the lateral side of the thorax after removing the hair either by clipping or by the application of a depilatory agent, according to a two-way crossover design. No potential adverse effects induced by the patches were observed in either group. In dogs with clipped hair, a mean peak plasma lidocaine concentration of 62.94 ng/ml was obtained after 10.67 h. In the depilatory group, a mean peak plasma concentration of 103.55 ng/ml was reached after 9.27 h. Significant differences in the AUC(0 ->infinity) C-max, k(a) and T-1/2a were noticed between the two groups. No significant differences were found for the elimination parameters and for T-max. In the second experiment, the patches were applied for 60 h to the clipped skin in order to study the absorption kinetics after a prolonged application period. There, the mean peak lidocame plasma concentration was 45.18 ng/ml achieved after 24 h and a final concentration of 29.37 ng/ml was obtained at 60h. In conclusion, all dogs tolerated the transdermal lidocaine patch well. The results of this study suggest that there is an overall minimal absorption from the lidocaine patch. However, the application of a depilatory agent leads to a more rapid and increased absorption of lidocame.
KeyWords Plus: PLASMA FENTANYL CONCENTRATIONS; MINIMUM ALVEOLAR CONCENTRATION; NEUROPATHIC PAIN; INTRAVENOUS LIDOCAINE; TRANSDERMAL PATCHES; ACTIVE METABOLITES; TOLERABILITY; INFUSION; CATS; PENETRATION
Addresses: Weiland L (reprint author), Univ Ghent, Fac Vet Med, Dept Surg & Anaesthesiol Domest Anim, Salisburylaan 133, Merelbeke, B-9820 Belgium Univ Ghent, Fac Vet Med, Dept Surg & Anaesthesiol Domest Anim, Merelbeke, B-9820 Belgium Univ Ghent, Fac Vet Med, Dept Pharmacol Pharm & Toxicol, Merelbeke, B-9820 Belgium Univ Ghent, Fac Vet Med, Dept Med & Clin Biol Small Anim, Merelbeke, B-9820 Belgium E-mail Addresses: lindaweil@hotmail.com Publisher: BLACKWELL PUBLISHING, 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND
Response 10
I have done a project involving the Lidoderm patch and horses. My primary project involved looking for systemic concentrations of lidocaine after two patches were placed on horses (which we found none) - this paper is still in review. Prior to the primary project, I tried the patch on people with arthritis, joint pain, (on myself after a particularly nasty rope burn accident involving a horse and my arm) and many different equine cases and some canine cases. These are some of the findings and facts: (I apologize for a disorganized summary)
1. The patch is unusual in that the lidocaine is suspended in a gel on a felt backing, therefore the patch can be cut to any size desired. Each 10x14cm patch contains 700mg lidocaine and the larger the surface area covered, the more lidocaine will be absorbed. Still, only 3% of what is in contact with the skin will get across the skin.
2. The patch does not appear to be effective at the A-beta fibers but instead at A-delta. Therefore, normal sensation is maintained but the pain fibers are affected (but only 3-4mm deep in people).
3. The patch was designed for post-herpetic neuralgia in humans by Endo Pharmaceuticals and has also been shown to be effective in all sorts of neuropathic pain, arthritis, back pain (in humans). The human recommendation is 12 hours on with 12 hours off before another patch is placed. In horses, we found that detected systemic therapeutic concentrations are not achieved, even with 2 patches continuously replaced every 12 hours for two weeks. It appears that the effects are localized and not due to sytemic concentrations.
4. The patch needs to be placed only once on clean, dry skin. Part of the mechanism is the binding of the gel with skin. It is not as effective if removed and replaced. A bandage over the area helps when placed on limbs.
5. As part of my preliminary study I looked at the patch on people with joint arthritis, back pain (the volunteers were very happy with the results) and also tried it as a palmar digital nerve block in horses. The horse trial involved a force plate and the patch did not work as a local block, but it did show a measurable effect in a horse with carpal arthritis. I also tried the patch on a horse with what was suspected as unilateral fetlock arthritis but he would not block out prior to trying the patch. It appeared that this horse had some tendon pathology but I tried the patch regardless and over the force plate there was no change after one day. The interesting thing was that the owners reported that the horse was more sound than ever for one month after (not sure if it was due to the patch but would like to think so).
6. We tried the patch on an obese (175 lb) Labarador Retriever after a pelvic fracture. Systemic analgesics were not adequate and placement of two to three patches appeared to help.
7. We tried the patch on a foal with septic arthritis of a stifle. After a single patch was placed (using tissue glue on the edges) over the stifle, the foal's lameness was 90% improved within 30 minutes of placement, this lasted 11 hours. We also tried the patch on a laminitis horse and it seemed to help for up to 11 hours before the effect wained.
8. There were no adverse effects noticed in any of the animals except mild-moderate erythema at the location of patch placement, this resolved when the patch was removed.
I have not tried the patch on cats and wonder if anyone has? It is easy to cut the patches to an appropriate size for any location or patient. I hope this helps! Please feel free to contact me if you have any further questions.
Lori Bidwell