RE: Tramadol

Neil Wheadon — Thu, 30 Jul 2020 18:52:26 GMT

Thankyou both

The acute verses chronic is interesting, maybe I'll use it in chronic cases but as you say which ones?

As a locum I see it used regularly in caesarian sections which is an interesting choice as mainstream ones have contraindications so Tramadol is used. I'll have to have a look at the data sheets now that licensed

Neil

RE: Tramadol

Carl Bradbrook — Thu, 30 Jul 2020 08:00:03 GMT

Hi Neil,

I would echo very much Dan's comments on tramadol. We published a review of acute pain management in dogs and cats in 2018 and our conclusion was that there is no evidence currently to support the use of tramadol in dogs for treatment of acute pain (there are many other effective options), but it could have a place in cats, although generally palatability is a problem I have noted.

In the chronic pain setting I agree completely with Dan, I have had good success with tramadol use in dogs, but it is very much down to good client communication and patient assessment. It will not suit every case, or every owner. I always follow up to make sure the client assess it to be effective, using a CMI/QOL tool and as Dan mentions it may not be until it is withdrawn that an owner realises it was beneficial. There are clinicians supporting the use of tramadol in the chronic setting for its non-opioid effects, where it may have a benefit on behavioural aspects of pain, particularly as it is a weak opioid and the opioid effects are so variable depending on its metabolism in the individual.

Carl

RE: Tramadol

Dan Holden — Wed, 29 Jul 2020 19:54:30 GMT

Hi Neil

Tramadol is very much a drug that seems to polarise some clinicians when discussing its efficacy. This is not helped by the relative paucity of well-designed and sufficiently robust studies exploring its use in the clinical setting, and variable findings in those studies that are in the literature.

Briefly, tramadol itself is a weak mu-receptor agonist with active metabolites that probably have effects at many (if not all) opioid receptors. It also inhibits re-uptake of 5-HT & noradrenaline and enhances presynaptic release of 5-HT, which may explain some of its analgesic benefits. The major metabolite (O-desmethytramadol or ODT) is apparently produced more rapidly and to a greater degree in dogs than in humans, but is cleared more rapidly. Cats produce ODT but (unsurprisingly) clear it less rapidly. In humans "slow" and "fast"metabolisers have been identified; there is some evidence that this is the case in dogs.

Clinically, there are studies that demonstrate some benefit, and those that don't. This is a very small selection:

Pharmacokinetics and antinociceptive effects of oral tramadol hydrochloride administration in Greyhounds.

Am J Vet Res. February 2011;72(2):256-62.

Article Abstract

OBJECTIVE: To determine the pharmacokinetics of tramadol, the active metabolite O-desmethyltrcamadol, and the metabolites N-desmethyltramadol and N,O-didesmethyltramadol after oral tramadol administration and to determine the antinociceptive effects of the drug in Greyhounds.

ANIMALS: 6 healthy 2- to 3-year-old Greyhounds (3 male and 3 female), weighing 25.5 to 41.1 kg.

PROCEDURES: A mean dose of 9.9 mg of tramadol HCl/kg was administered PO as whole tablets. Blood samples were obtained prior to and at various points after administration to measure plasma concentrations of tramadol and its metabolites via liquid chromatography with mass spectrometry. Antinociceptive effects were determined by measurement of pain-pressure thresholds with a von Frey device.

RESULTS: Tramadol was well tolerated, and a significant increase in pain-pressure thresholds was evident 5 and 6 hours after administration. The mean maximum plasma concentrations of tramadol, O-desmethyltramadol, N-desmethyltramadol, and N,O-didesmethyltramadol were 215.7, 5.7, 379.1, and 2372 ng/mL, respectively. The mean area-under-the-curve values for the compounds were 592, 16, 1,536, and 1,013 h·ng/mL, respectively. The terminal half-lives of the compounds were 1.1, 1.4, 2.3, and 3.6 hours, respectively. Tramadol was detected in urine 5 days, but not 7 days, after administration.

CONCLUSIONS AND CLINICAL RELEVANCE: Oral tramadol administration yielded antinociceptive effects in Greyhounds, but plasma concentrations of tramadol and O-desmethyltramadol were lower than expected. Compared with the approved dose (100 mg, PO) in humans, a mean dose of 9.9 mg/kg, PO resulted in similar tramadol but lower O-desmethyltramadol plasma concentrations in Greyhounds.

Comparison of carprofen and tramadol for postoperative analgesia in dogs undergoing enucleation.

J Am Vet Med Assoc. December 2014;245(12):1375-81.

Article Abstract

OBJECTIVE: To compare analgesia provided by carprofen and tramadol in dogs after enucleation.

DESIGN: Randomized, masked clinical trial.

ANIMALS: 43 dogs.

PROCEDURES: Client-owned dogs admitted for routine enucleation were randomly assigned to receive either carprofen or tramadol orally 2 hours prior to surgery and 12 hours after the first dose. Dogs were scored for signs of pain at baseline (ie, before carprofen or tramadol administration) and at 0.25, 0.5, 1, 2, 4, 6, 8, 24, and 30 hours after extubation. Dogs received identical premedication and inhalation anesthesia regimens, including premedication with hydromorphone. If the total pain score was ≥ 9 (maximum possible score of 20), there was a score ≥ 3 in any of 5 behavioral categories (highest score possible per category was 3 or 4), or the visual analog scale (VAS) score was ≥ 35 (maximum possible score of 100) combined with a palpation score > 0, rescue analgesia (hydromorphone) was administered and treatment failure was recorded.

RESULTS: No differences were found in age, sex, or baseline pain scores between groups. Significantly more dogs receiving tramadol required rescue analgesia (6/21), compared with dogs receiving carprofen (1/22). Pain and VAS scores decreased linearly over time. No significant differences were found in pain or VAS scores between groups at any time point (dogs were excluded from analysis after rescue).

CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that carprofen, with opioid premedication, may provide more effective postoperative analgesia than tramadol in dogs undergoing enucleation.

Effects of tramadol alone, in combination with meloxicam or dipyrone, on postoperative pain and the analgesic requirement in dogs undergoing unilateral mastectomy with or without ovariohysterectomy.

Vet Anaesth Analg. November 2013;40(6):641-9.

Article Abstract

OBJECTIVE:To compare the effects of tramadol alone, or in combination with dipyrone or meloxicam, on postoperative pain and analgesia requirement after unilateral mastectomy with or without ovariohysterectomy in dogs.

STUDY DESIGN:Prospective, randomized, clinical study.

ANIMALS:Twenty seven bitches undergoing unilateral mastectomy with or without ovariohysterectomy.

METHODS:Anesthesia was induced with propofol and maintained with isoflurane and a constant rate infusion of morphine. Before the end of surgery, dogs were randomly assigned to receive intravenous tramadol alone (3 mg kg(-1), group T), combined with dipyrone (30 mg kg(-1), group TD) or meloxicam (0.2 mg kg(-1), group TM). Dogs received additional doses of tramadol (groups T and TM) or tramadol with dipyrone (group TD) at 8 and 16 hours after extubation. Postoperative pain was assessed by a blinded observer before anesthesia (baseline) and at 1, 2, 3, 4, 6, 8, 12, 16 and 24 hours after extubation using a visual analog scale (VAS) and a modified Glasgow scale. Rescue analgesia (morphine, 0.5 mg kg(-1)) was administered if the Glasgow pain score was >3.5.

RESULTS:There were no significant differences among groups in pain scores evaluated by the VAS or the Glasgow scale. In groups T, TD and TM, pain scores were significantly higher than at baseline for 6, 8 and 2 hours, respectively. Rescue analgesia was administered to 3/9, 2/9 and 1/9 dogs in groups T, TD and TM, respectively (p > 0.05) [Correction added on 15 August 2013, after first online publication: 'T, TM and TD' was changed to 'T, TD and TM'.].

CONCLUSIONS AND CLINICAL RELEVANCE:Under the conditions of this study, tramadol alone or in combination with dypyrone or meloxicam provided effective analgesia for 24 hours in most dogs after unilateral mastectomy with or without ovariohysterectomy. Further evaluation of combination therapies is needed in larger groups of dogs.

There are several studies which suggest no or little benefit, but no really large-scale well-designed studies. It's been given by most routes (including intra-abdominal, epidural, intra-articular) but oral is most common.

My take-home thoughts would probably be:

1. Dose three times daily (dogs: 5mg/kg po, cast 2-4mg/kg po; some clinicans use much higher doses)

2. Use it as an adjunct analgesic, commonly with NSAIDs, not on its own

3. Monitor the efficacy (and side-effects) and be prepared to alter the dose. Cats appear very variable in their response to tramadol and may be difficult to medicate as the drug in all forms is extremely bitter.

4. In my hands tramadol seems more useful for chronic pain rather that acute perioperative pain. There is the inherent issue of confusing "sedation" with analgesia; scoring systems may prove helpful in this regard.

5. It will work well in some patients and appear to not work at all in others. To many clients its effects on their animals are sometimes only apparent when they stop giving it due to lack of perceived benefit.....

Not sure how much help this is to you!

Cheers

Dan