Use of Negative Pressure Wound Therapy in the Treatment of Limb Wounds: A Case Series of 42 Horses.

Traumatic limb injuries are common in horses. Negative pressure wound therapy (NPWT) has been proven to promote wound healing in human medicine. It has also been described for the treatment of wounds in horses. In this retrospective study, clinical records of 42 (n = 42) animals were assessed. Categories of wounds, duration of NPWT application, frequency of resetting the NPWT device, technical complications, and tolerance to the procedure were recorded. 42 wounds were classified as bony (n = 15; 36 %), articular (n = 14; 33 %), tenosynovial (n = 9; 21%), muscular (n = 2; 5%) and cutaneous (n = 2; 5 %). NPWT was used to help (1) first intention healing by preoperative (n = 3; 7 %) or postoperative (n = 7; 17%) application, (2) second intention healing (n = 31; 74%), and (3) delayed primary closure (n = 1; 2%). Duration of NPWT application ranged from 2 to 36 days (mean 11.5), with the system staying in place for periods ranging from 1 to 7 days (mean 4.5). In 69% (n = 29) of the cases, healing was considered satisfactory at discharge. 26 % (n = 11) of horses were discharged whilst ideally NPWT should have been continued. 2 animals (n = 2; 5%) were euthanized after surgery due to unrelenting pain. The procedure was well tolerated except in 1 horse who showed signs of discomfort at the first application. This study demonstrated that NPWT with long periods of application can be used successfully to manage various types of limb wounds.

Efficacy of extended-release tramadol for treatment of prescription opioid withdrawal: a two-phase randomized controlled trial.

BACKGROUND: Tramadol is an atypical analgesic with monoamine and modest mu opioid agonist activity. The purpose of this study was to evaluate: (1) the efficacy of extended-release (ER) tramadol in treating prescription opioid withdrawal and (2) whether cessation of ER tramadol produces opioid withdrawal. METHODS: Prescription opioid users with current opioid dependence and observed withdrawal participated in this inpatient, two-phase double blind, randomized placebo-controlled trial. In Phase 1 (days 1-7), participants were randomly assigned to matched oral placebo or ER tramadol (200 or 600 mg daily). In Phase 2 (days 8-13), all participants underwent double blind crossover to placebo. Breakthrough withdrawal medications were available for all subjects. Enrollment continued until 12 completers/group was achieved. RESULTS: Use of breakthrough withdrawal medication differed significantly (p<0.05) among groups in both phases; the 200mg group received the least amount in Phase 1, and the 600 mg group received the most in both phases. In Phase 1, tramadol 200mg produced significantly lower peak ratings than placebo on ratings of insomnia, lacrimation, muscular tension, and sneezing. Only tramadol 600 mg produced miosis in Phase 1. In Phase 2, tramadol 600 mg produced higher peak ratings of rhinorrhea, irritable, depressed, heavy/sluggish, and hot/cold flashes than placebo. There were no serious adverse events and no signal of abuse liability for tramadol. CONCLUSIONS: ER tramadol 200mg modestly attenuated opioid withdrawal. Mild opioid withdrawal occurred after cessation of treatment with 600 mg tramadol. These data support the continued investigation of tramadol as a treatment for opioid withdrawal.

Abuse liability and reinforcing efficacy of oral tramadol in humans.

BACKGROUND: Tramadol, a monoaminergic reuptake inhibitor, is hepatically metabolized to an opioid agonist (M1). This atypical analgesic is generally considered to have limited abuse liability. Recent reports of its abuse have increased in the U.S., leading to more stringent regulation in some states, but not nationally. The purpose of this study was to examine the relative abuse liability and reinforcing efficacy of tramadol in comparison to a high (oxycodone) and low efficacy (codeine) opioid agonist. METHODS: Nine healthy, non-dependent prescription opioid abusers (6 male and 3 female) participated in this within-subject, randomized, double blind, placebo-controlled study. Participants completed 14 paired sessions (7 sample and 7 self-administration). During each sample session, an oral dose of tramadol (200 and 400 mg), oxycodone (20 and 40 mg), codeine (100 and 200 mg) or placebo was administered, and a full array of abuse liability measures was collected. During self-administration sessions, volunteers were given the opportunity to work (via progressive ratio) for the sample dose or money. RESULTS: All active doses were self-administered; placebo engendered no responding. The high doses of tramadol and oxycodone were readily self-administered (70%, 59% of available drug, respectively); lower doses and both codeine doses maintained intermediate levels of drug taking. All three drugs dose-dependently increased measures indicative of abuse liability, relative to placebo; however, the magnitude and time course of these and other pharmacodynamic effects varied qualitatively across drugs. CONCLUSIONS: This study demonstrates that, like other mu opioids, higher doses of tramadol function as reinforcers in opioid abusers, providing new empirical data for regulatory evaluation.

Intranasal oxycodone self-administration in non-dependent opioid abusers.

Oxycodone, an opioid with known abuse liability, is misused by the intranasal route. Our objective was to develop a model of intranasal oxycodone self-administration useful for assessing the relative reinforcing effects of opioids and potential pharmacotherapies for opioid use disorders. Healthy, sporadic intranasal opioid abusers (n = 8; 7 M, 1 F) completed this inpatient 2.5-week, randomized, double-blind, placebo-controlled, crossover study. Each intranasal oxycodone dose (0, 14 & 28 mg) was tested in a separate 3-day block of sessions. The first day of each block was a sample session in which the test dose was given. Two randomized progressive ratio sessions were conducted on the next 2 days: (1) subjects could work for the test dose over 7 trials (1/7th of total dose/trial), and (2) subjects could work for either a portion of the dose (1/7th) or money ($3) over 7 trials. Physiological and subjective measures were collected before and after drug administration for all sessions. Subjects never worked to self-administer placebo regardless of whether money was available. In both self-administration sessions, oxycodone self-administration was dose-dependent. Subjects worked less for drug (28 mg oxycodone) when money was available but only modestly so. Oxycodone dose-dependently increased VAS ratings of positive drug effects (e.g., "like") during sample sessions (p < .05). These reports were positively correlated with self-administration behavior (e.g., "like," r = .65). These data suggest that both procedures are sensitive for detecting the reinforcing properties of intranasal oxycodone and may be used to further explore the characteristics of opioid compounds and potential pharmacotherapies for treatment.

Pharmacodynamic profile of tramadol in humans: influence of naltrexone pretreatment.

RATIONALE: Tramadol is a prescription analgesic that activates mu opioid and monoamine receptor systems. Tramadol is thought to have limited abuse potential compared to mu opioid agonists, but laboratory data indicate that it shares some of their pharmacodynamic effects. OBJECTIVES: This study evaluated the effect of mu opioid receptor blockade with naltrexone on the pharmacodynamic action of tramadol in humans. METHODS: This inpatient, double-blind, randomized, within-subject study examined the effects of oral placebo, tramadol (87.5, 175, and 350 mg), and hydromorphone (4 and 16 mg; positive control) after 1 h pretreatment with oral naltrexone (0 and 50 mg). Ten recreational opioid users completed the study. Pharmacodynamic effects were measured before and for 7 h after initial drug administration. RESULTS: Lower doses of tramadol and hydromorphone were generally placebo-like. Hydromorphone (16 mg) produced prototypic mu opioid agonist-like effects that were blocked by naltrexone. Tramadol (350 mg) produced miosis and increased ratings of "Good Effects" and "Liking" but also increased ratings of "Bad Effects." Naltrexone reversed tramadol-induced physiological effects and mydriasis emerged, but unlike results with hydromorphone, naltrexone only partially attenuated tramadol's positive subjective effects and actually enhanced several unpleasant subjective ratings. CONCLUSIONS: Naltrexone can be used to disentangle the mixed neuropharmacological actions of tramadol. High-dose tramadol produces a mixed profile of effects. These data suggest that both mu and non-mu opioid actions play a role in tramadol's subjective profile of action.