Louis Greeff, [16 Apr 2023 at 07:29:14]: Good morning I darted 9 zebra yesterday, using 3mg etorphine, 6mg medetomidine and 20mg azaperone and Hyalase. They went down in 3 to 4min. I gave 20mg water-based perphenazine (perphenazine hydrochloride/ WBP), 3ml V-Tech Atipamezole/ Yohimbine mixture im, and 40mg naltrexone im. They went from Groblersdal to Tosca. Everything was fine for 8h, all were standing and relaxed. Between 8 and 9 h after being loaded, two animals that were loaded in single compartments went down on their sides. They were just lying there, relaxed, but their eyes were a bit wild. Both died just before offloading. One male on offloading, climbed off and ran in circles until he hit a tree and broke his neck. The rest were all very relaxed. This is the first time I experienced something like this,. Might it be the perphenazine? Any experience with water-based perphenazine in zebra? Any other thoughts? Henry Labuschagne, [16 Apr 2023 at 09:38:47]: Sorry to hear Louis. Don't beat yourself up. Bad things happen to good guys. I think there was an issue with azaperone and water-based perphenazine (WBP). If I am going to use WBP for longer tranquilisation, I only use WBP and not azaperone. I then use WBP in dart. Neil Parsons, [16 Apr 2023 at 09:48:37]: Hi Louis, I routinely use 60-70mg of WBP in adult zebra with no issues. I have also used azaperone and WBP in them without issues. Anything of note on PM? Louis Greeff, [16 Apr 2023 at 11:09:25]: I spoke to the transporter at length now. Everything was fine for about 8h. They all stood and were relaxed, they looked like horses with medetomidine. When they opened the latches on top, they lifted their heads and turned around, which is normal behaviour. They checked in Pretoria, Koster, Sannieshof, and then in Vryburg, the one was down lying on its side. Normal breathing, no muscle rigidity - the eyes were just a bit bewildered. He went back into sternal recumbency. They left him like that. On offloading, he was dead. The other male in the other single compartment was also lying down. They pulled him out, he died a half an hour later. There was no excitement, just lying down and stopped breathing. The other one was beserk – it climbed out, ran into objects and eventually ran into a tree, and died. Any thoughts? They have opened the carcasses up, but nothing abnormal. Not one bruise to the head, no lung issues. The rest is normal. Louis Greeff, [16 Apr 2023 at 15:30:17]: Neil, how long do you transport them? Do you transport them always together? That is what I usually do, but the size of the compartments forced me to let the stallions stand alone. Henry, that was my first concern also, but I did a lot of them with the same protocol without any hassles. My first question to the transporter was didn’t they react abnormally such as head swinging, or head pressing. His answer was that they were perfectly calm for 8 hours, and reacted when latches were opened to inspect them. Then within 2 hours the wheels came off. My personal opinion is that it has to do with the water-based perphenazine, either in combination with the medetomidine or azaperone.By 8 hours post darting, all the other drugs shouldn’t have effect anymore, with only the perphenazine hydrochloride being active. I appreciate all your thoughts. Henry Labuschagne, [16 Apr 2023 at 18:15:11]: The WBP @ 20mg was low and should not cause issues even with the azaperone in the dart. I use 50mg minimum. I am also in the dark on this one. HO Reuter, [17 Apr 2023 at 07:40:18]: Very strange! What was the temperature/ ventilation in crates like? In the past I used 5-7 mg etorphine with 5 mg medetomidine and no atipamezole, only Trexonil reversal. Using 6 mg medetomidine, I cannot see that medetomidine can cause this after 8 hours. Even with low dose perphenazine, this makes no sense. Leith Meyer, [17 Apr 2023 at 08:50:58]: I would consider renarcotisation related to a low dose of naltrexone (13mg to 1 mg etorphine). Etorphine can cause severe sympathetic nervous system activation, especially in equids, and while the other drugs may have made the animals look calm on the outside, their physiology may have been “overloaded” on the inside. Neil Parsons, [17 Apr 2023 at 15:15:55]: Hi Louis. We often transport zebra for 24 hours or more, usually in groups though. We do have mortalities, but almost always due to inadequate tranquilisation (or sometimes mixing of groups), resulting in traumatic injuries. Our drivers are not scared to report issues to us, so they always tell us about individuals that are fighting/jumping. My first thought was traumatic injury when you mentioned those tranquilisation doses and animals in individual compartments. I don’t think the absence of bruising in the subcutaneous area/muscle around the head/neck area is enough to rule out deeper traumatic injury from head/neck twisting, excessive flexion/extension or impact. Unless the cranium was opened and cervical spinal cord examined, then it's hard to know for sure. If you really trust your transporter, then perhaps this isn’t a possibility. If it was an overdose reaction to the tranquiliser, then I’d expect the other healthy animals to at least show some abnormal signs? I do like the renarcotisation theory for this case too. Louis Greeff, [17 Apr 2023 at 20:52:37]: Thanks for all the thoughts. Leith, I always use 10mg naltrexone to 1mg opioid. What would you recommend then is the right dose? Wouldn’t renarcotisation cause animals to press or go down? I still wait for the pm videos. I will look myself and let you know Ventilation was fine and it was not a hot day at all Ben Muller, [17 Apr 2023 at 21:25:05]: Hi Louis. This might be off topic here, but I lost some zebra once due to “transport tetany”. Animals we in quite small compartments (poor ventilation) hot conditions, very poor dirt roads and lots of dust (800km, 33 hour delivery) that resulted in severe physiological derangements and their death. Your trip doesn’t sound half as bad but also worth considering our animals transport conditions. This could compound on other issues that HO and Leith mentioned. Rick Last confirmed on this on histopathology in this case Ulf Tubessing, [17 Apr 2023 at 21:34:25]: Hi Louis. I often move zebras for up to 5-6 days on truck with no problems. I use up to 70 mg of WBP in dart cocktail but no azaperone. Leith Meyer, [17 Apr 2023 at 21:43:57]: Hi Louis. Naltrexone 10:1 dose is fine for thiafentanil since it is shorter acting than etorphine. For etorphine, 20:1 is best. The lower the dose of naltrexone, the greater the risk of renarcotisation and the sooner after reversal it occurs. Louis Greeff, [17 Apr 2023 at 22:03:54]: Leith, you have definitely taught me something. Thank you. Thanks for all the other thoughts. HO Reuter, [17 Apr 2023 at 22:12:29]: Would renarcotisation occur so long after reversal? In my experience, zebra (and elephant) seem to metabolise etorphine quicker than most other species and need an opioid top-up if immobilised for long. Would a lot of the etorphine not be metabolised already 8 hours later? Leith, is diprenorphine a longer acting and preferred reversal agent for etorphine (even though a partial agonist)? Leith Meyer, [18 Apr 2023 at 05:53:21]: It may be, but there’s also entero-hepatic recycling and redistribution from fat that could cause a prolonged “tail” of the effect. There is obviously also individual variation between animals of the same species, especially when it comes to metabolism. I’m not 100% sure, but I think the duration of effect is fairly similar between diprenorphine and naltrexone. The key thing with these drugs is because they are competitive antagonists, the dose needs to be high enough to maintain an adequate antagonistic effect until etorphine is mostly eliminated from the body. Leith Meyer, [18 Apr 2023 at 08:26:38]: HO, maybe just to add, that it is believed that naltrexone has a longer duration of effect as it didn’t cause renarcotisation when used to antagonize carfentanil, but diprenorphine did. However, the dose of naltrexone used for carfentanil is very high 40:1. So I think the verdict is still out there as to the actual duration of effect of these two drugs, but as mentioned already, this duration can easily be manipulated by changing the dose of both of these drugs. For those interested in gaining more insights related to renarcotisation, see the publication by Jacques o'Dell : Pierre Nel, [28 Apr 2023 at 11:56:27]: I agree with Neil. They are very prone to cervical subluxation, and the fact that it happened some hours into the journey may indicate that sedation was wearing off slightly and they jumped against the roof. Running in circles after offloading might be from very slight spinal cord damage but then hitting the tree did the final damage. If very specific intentional dissection of the neck from skull to about C3 is not done, it can easily be missed. Henry Labuschagne, [28 Apr 2023 at 12:25:44]: Yes, I agree. I had a nyala bull with same history as the zebra. At offloading he was fine. Went down on day 2. PM # caudal c2 I suspected spinal trauma. On clinical manipulation I could not feel any crepitation or anything abnormal. This bull took off after being darted and tripped over a 4' fence but got up fine and ran for 100m without any symptoms.