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Caring for patients with opioid use disorder in the hospital.

Tue, 04/04/2017 - 7:08am
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Caring for patients with opioid use disorder in the hospital.

CMAJ. 2016 Dec 06;188(17-18):1232-1239

Authors: Donroe JH, Holt SR, Tetrault JM

PMID: 27647616 [PubMed - indexed for MEDLINE]

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Buprenorphine physician supply: Relationship with state-level prescription opioid mortality.

Sun, 04/02/2017 - 7:56am
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Buprenorphine physician supply: Relationship with state-level prescription opioid mortality.

Drug Alcohol Depend. 2017 Apr 01;173 Suppl 1:S55-S64

Authors: Knudsen HK, Havens JR, Lofwall MR, Studts JL, Walsh SL

Abstract
BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder but the supply of buprenorphine physicians is currently inadequate to address the nation's prescription opioid crisis. Perception of need due to rising opioid overdose rates is one possible reason for physicians to adopt buprenorphine. This study examined associations between rates of growth in buprenorphine physicians and prescription opioid overdose mortality rates in US states.
METHODS: The total buprenorphine physician supply and number of physicians approved to treat 100 patients (per 100,000 population) were measured from June 2013 to January 2016. States were divided into two groups: those with rates of prescription opioid overdose mortality in 2013 at or above the median (>5.5 deaths per 100,000 population) and those with rates below the median. State-level growth curves were estimated using mixed-effects regression to compare rates of growth between high and low overdose states.
RESULTS: The total supply and the supply of 100-patient buprenorphine physicians grew significantly (total supply from 7.7 to 9.9 per 100,000 population, p<0.001; 100-patient supply from 2.2 to 3.4 per 100,000 population, p<0.001). Rates of growth were significantly greater in high overdose states when compared to low overdose states (total supply b=0.033, p<0.01; 100-patient b=0.022, p<0.01).
CONCLUSIONS: The magnitude of the US prescription opioid crisis, as measured by the rate of prescription opioid overdose mortality, is associated with growth in the number of buprenorphine physicians. Because this observational design cannot establish causality, further research is needed to elucidate the factors influencing physicians' decisions to begin prescribing buprenorphine.

PMID: 28363321 [PubMed - in process]

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The Prescription Opioid Addiction Treatment Study: What have we learned.

Sun, 04/02/2017 - 7:56am
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The Prescription Opioid Addiction Treatment Study: What have we learned.

Drug Alcohol Depend. 2017 Apr 01;173 Suppl 1:S48-S54

Authors: Weiss RD, Rao V

Abstract
BACKGROUND: The multi-site Prescription Opioid Addiction Treatment Study (POATS), conducted by the National Drug Abuse Treatment Clinical Trials Network, was the largest clinical trial yet conducted with patients dependent upon prescription opioids (N=653). In addition to main trial results, the study yielded numerous secondary analyses, and included a 3.5-year follow-up study, the first of its kind with this population. This paper reviews key findings from POATS and its follow-up study.
METHODS: The paper summarizes the POATS design, main outcomes, predictors of outcome, subgroup analyses, the predictive power of early treatment response, and the long-term follow-up study.
RESULTS: POATS examined combinations of buprenorphine-naloxone of varying duration and counseling of varying intensity. The primary outcome analysis showed no overall benefit to adding drug counseling to buprenorphine-naloxone and weekly medical management. Only 7% of patients achieved a successful outcome (abstinence or near-abstinence from opioids) during a 4-week taper and 8-week follow-up; by comparison, 49% of patients achieved success while subsequently stabilized on buprenorphine-naloxone. Long-term follow-up results were more encouraging, with higher abstinence rates than in the main trial. Patients receiving opioid agonist treatment at the time of follow-up were more likely to have better outcomes, though a sizeable number of patients succeeded without agonist treatment. Some patients initiated risky use patterns, including heroin use and drug injection. A limitation of the long-term follow-up study was the low follow-up rate.
CONCLUSIONS: POATS was the first large-scale study of the treatment of prescription opioid dependence; its findings can influence both treatment guidelines and future studies.

PMID: 28363320 [PubMed - in process]

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Pressure sensitivity and phenotypic changes in patients with suspected opioid-induced hyperalgesia being withdrawn from full mu agonists.

Sat, 04/01/2017 - 7:07am
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Pressure sensitivity and phenotypic changes in patients with suspected opioid-induced hyperalgesia being withdrawn from full mu agonists.

J Nat Sci. 2017 Feb;3(2):

Authors: Wasserman RA, Hassett AL, Harte SE, Goesling J, Malinoff HL, Berland DW, Zollars J, Moser SE, Brummett CM

Abstract
OBJECTIVES: To assess changes in phenotype and pressure sensitivity in patients with suspected opioid-induced-hyperalgesia (OIH) after transitioning to buprenorphine.
METHODS: Twenty patients with suspected OIH were enrolled to transition to buprenorphine therapy. Patients completed validated self-report measures at baseline and at 1, 4, 8 weeks, and 6 months after initiation of buprenorphine along with quantitative sensory testing including measures of pressure pain threshold, pain tolerance and Pain 50 (a pain intensity rating).
RESULTS: 20 patients were enrolled, 17 were treated with buprenorphine and 11 completed all assessment points. We found that after transitioning to buprenorphine, patients on higher opioid doses (≥100mg oral morphine equivalents) had significant improvements for some measures including decreased pain severity and fibromyalgia survey scores, fewer neuropathic pain features, less catastrophizing, fewer depressive symptoms, and improved functioning 1-week after transitioning to buprenorphine with an eventual return back to baseline. Although not statistically significant, patients on high dose opioids (≥100mg OME) also showed a trend of decreased pressure sensitivity 1-week after transitioning to buprenorphine with a gradual return back to baseline.
CONCLUSIONS: Our study is the first to look at pressure pain sensitivity in patients who were taking opioids and transitioned to buprenorphine. These results suggest that the patients most likely to benefit from buprenorphine therapy are those on higher doses. In addition, the eventual return back to baseline on measures of pain phenotype and pressure sensitivity suggests that buprenorphine may over time result in a return of the hyperalgesic effects of a full mu agonist.

PMID: 28361126 [PubMed - in process]

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Definitive Drug and Metabolite Screening in Urine by UPLC-MS-MS Using a Novel Calibration Technique.

Sat, 04/01/2017 - 7:07am
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Definitive Drug and Metabolite Screening in Urine by UPLC-MS-MS Using a Novel Calibration Technique.

J Anal Toxicol. 2016 Oct;40(8):628-638

Authors: Rosano TG, Ohouo PY, LeQue JJ, Freeto SM, Wood M

Abstract
Drug screening is an essential analytical tool for detection of therapeutic, illicit and emerging drug use. Presumptive immunoassay screening is widely used, while initial definitive testing by chromatography-coupled mass spectrometry is hampered due to complex pre-analysis steps, long chromatography time and matrix effects. The aim of this study is to develop and validate a definitive test for rapid and threshold accurate screening of 33 drugs or metabolites (analytes) in urine. Sample preparation in a 96-well plate format involves rapid glucuronidase hydrolysis followed by dilution, filtration and ultra-performance liquid chromatography-MS-MS analysis. Chromatographic separation, on an ACQUITY UPLC(®) BEH phenyl column is optimized for a 3-min MS-MS ion acquisition. Matrix effect was normalized by an innovative technique called threshold accurate calibration employing an additional analysis with an analyte spike as an internal standard undergoing the same matrix effect as an analyte in a drug-positive donor specimen. Accuracy and precision, at above and below threshold concentrations, were determined by replicate analysis of control urine pools containing 50, 75, 125 and 150% of threshold concentrations. Accuracy and selectivity were further demonstrated by concordant findings in proficiency and confirmatory testing. The study shows the applicability of definitive testing as an alternative to immunoassay screening and demonstrates a new approach to normalization of matrix effect.

PMID: 27562968 [PubMed - indexed for MEDLINE]

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Safety of a Rapidly Dissolving Buprenorphine/Naloxone Sublingual Tablet (BNX-RDT) for Treatment of Opioid Dependence: A Multicenter, Open-label Extension Study.

Thu, 03/30/2017 - 6:43am

Safety of a Rapidly Dissolving Buprenorphine/Naloxone Sublingual Tablet (BNX-RDT) for Treatment of Opioid Dependence: A Multicenter, Open-label Extension Study.

J Addict Med. 2017 Mar 28;:

Authors: Hoffman K, Peyton ML, Sumner M

Abstract
OBJECTIVE: To assess the safety of rapidly dissolving buprenorphine/naloxone sublingual tablets (BNX-RDT) in opioid-dependent patients.
METHODS: This open-label, 24-week extension study enrolled patients who completed primary trials of BNX-RDT. Daily tablet doses ranged from 5.7 to 17.1 mg. The primary endpoint was safety; secondary assessments included opioid cravings, addiction severity, health-related quality of life (QOL), and workplace productivity at screening (final day of the primary trials) through study end, with changes measured from baseline of the primary trials.
RESULTS: In all, 665 patients received treatment; 292 (43.9%) completed the study. A total of 258 patients (38.8%) reported 557 treatment-emergent adverse events, most commonly headache (3.2%) and constipation (3.0%). Craving scores showed continued improvement on 100-mm visual analog scale (mean change from primary trial baseline, -52.8 at screening; mean change from extension trial baseline, -60.5 at week 24). Reductions in addiction severity from baseline of both the primary and extension trial were maintained through week 24 on multiple assessments, as were improvements in QOL on Short Form 36. Employment increased by 15% and mean (SD) hours worked per week increased by 4.6 (20.1) from baseline to study end. Mean (SD) scores for impact of opioid dependence on work productivity improved from 4.7 (3.0) at baseline to 0.9 (1.8) at study end (11-point scale).
CONCLUSIONS: Extended treatment with BNX-RDT demonstrated a safety profile similar to other BNX formulations, reduced opioid cravings, and improved both QOL and work productivity. Continued treatment may enable patients to advance in recovery and return to normal functioning.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.

PMID: 28353467 [PubMed - as supplied by publisher]

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Commercial Health Plan Coverage of Selected Treatments for Opioid Use Disorders from 2003 to 2014.

Thu, 03/30/2017 - 6:43am
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Commercial Health Plan Coverage of Selected Treatments for Opioid Use Disorders from 2003 to 2014.

J Psychoactive Drugs. 2017 Mar 28;:1-9

Authors: Reif S, Creedon TB, Horgan CM, Stewart MT, Garnick DW

Abstract
Opioid use disorders (OUDs) are receiving significant attention in the U.S. as a public health crisis. Access to treatment for OUDs is essential and was expected to improve following implementation of the federal parity law and the Affordable Care Act. This study examines changes in coverage and management of treatments for OUDs (opioid treatment programs (OTPs) as a covered service benefit, buprenorphine as a pharmacy benefit) before, during, and after parity and ACA implementation. Data are from three rounds of a nationally representative survey conducted with commercial health plans regarding behavioral health services in benefit years 2003, 2010, and 2014. Data were weighted to be representative of health plans' commercial products in the continental United States (2003 weighted N = 7,469, 83% response rate; 2010 N = 8,431, 89% response rate; and 2014 N = 6,974, 80% response rate). Results showed treatment for OUDs was covered by nearly all health plan products in each year of the survey, but the types and patterns varied by year. Prior authorization requirements for OTPs have decreased over time. Despite the promise of expanded access to OUD treatment suggested by parity and the ACA, improved health plan coverage for treatment of OUDs, while essential, is not sufficient to address the opioid crisis.

PMID: 28350229 [PubMed - as supplied by publisher]

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Probuphine® (buprenorphine implant): a promising candidate in opioid dependence.

Thu, 03/30/2017 - 6:43am
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Probuphine® (buprenorphine implant): a promising candidate in opioid dependence.

Ther Adv Psychopharmacol. 2017 Mar;7(3):119-134

Authors: Barnwal P, Das S, Mondal S, Ramasamy A, Maiti T, Saha A

Abstract
Opioid dependence leads to physical dependence and addiction which finally results in profound medical, psychological and social dysfunction. One of the useful medications for opioid dependence is buprenorphine, the partial opioid agonist, which is used alone or in combination with naloxone. However, buprenorphine is the victim of its own success due to its illicit use and accidental poisoning in children. Also, buprenorphine typically requires daily self-administration and its effectiveness heavily depends on patient adherence. So, poor treatment adherence results in ineffective treatment manifesting as craving and withdrawal symptoms. Short-term use of buprenorphine in opioid dependence is also often followed by relapse. Buprenorphine when used sublingually often results in inadequate or fluctuating blood concentrations and poorer treatment retention compared with methadone. All of these led to the development of Probuphine®, a polymeric matrix composed of ethylene vinyl acetate and buprenorphine in the form of implants, that are implanted subdermally in office practice and deliver the active drug over 6 months. Buprenorphine release from such implant is fairly consistent, avoiding plasma peaks and troughs, and the implant is also reported to be safe. In this review article, we have highlighted these aspects of treatment of opioid addiction, stressing on the pharmacology of buprenorphine and Probuphine®, and relevant clinical trials addressing the efficacy and safety of Probuphine®. This sustained-release implantable formulation of buprenorphine has the potential to be a suitable alternative to daily or alternate day sublingual buprenorphine which can thereby eliminate the need for daily supervision, minimizing fluctuations in plasma concentrations, and allowing these patients to reduce clinic or pharmacy visits.

PMID: 28348732 [PubMed - in process]

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Bifunctional opioid/nociceptin hybrid KGNOP1 effectively attenuates pain-related behaviour in a rat model of neuropathy.

Thu, 03/30/2017 - 6:43am
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Bifunctional opioid/nociceptin hybrid KGNOP1 effectively attenuates pain-related behaviour in a rat model of neuropathy.

Eur J Pharm Sci. 2017 Mar 24;:

Authors: Starnowska J, Guillemyn K, Makuch W, Mika J, Ballet S, Przewlocka B

Abstract
A bifunctional peptide containing an opioid and nociceptin receptor-binding pharmacophore, H-Dmt-D-Arg-Aba-β-Ala-Arg-Tyr-Tyr-Arg-Ile-Lys-NH2 (KGNOP1), was tested for its analgesic properties when administered intrathecally in naïve and chronic constriction injury (CCI)-exposed rats with neuropathy-like symptoms. KGNOP1 significantly increased the acute pain threshold, as measured by the tail-flick test, and also increased the threshold of a painful reaction to mechanical and thermal stimuli in CCI-exposed rats. Both of the effects could be blocked by pre-administration of [Nphe1]-Nociceptin (1-13)-NH2 (NPhe) or naloxone, antagonists for nociceptin and opioid receptors, respectively. This led us to conclude that KGNOP1 acts as a dual opioid and nociceptin receptor agonist in vivo. The analgesic effect of KGNOP1 proved to be more powerful than clinical drugs such as morphine and buprenorphine. Repeated daily intrathecal injections of KGNOP1 led to the development of analgesic tolerance, with the antiallodynic action being completely abolished on day 6. Nevertheless, the development of tolerance to the antihyperalgesic effect was delayed in comparison to morphine, which lost its efficacy as measured by the cold plate test after 3days of daily intrathecal administration, whereas KGNOP1 was efficient up to day 6. A single intrathecal injection of morphine to KGNOP1-tolerant rats did not raise the pain threshold in any of the behavioural tests; in contrast, a single intrathecal dose of KGNOP1 significantly suppressed allodynia and hyperalgesia in morphine-tolerant rats.

PMID: 28347772 [PubMed - as supplied by publisher]

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Treatment with direct-acting antiviral agents of hepatitis C virus infection in injecting drug users: a prospective study.

Tue, 03/28/2017 - 9:07am
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Treatment with direct-acting antiviral agents of hepatitis C virus infection in injecting drug users: a prospective study.

J Viral Hepat. 2017 Mar 26;:

Authors: Boglione L, Mornese Pinna S, De Nicolò A, Cusato J, Cariti G, Di Perri G, D'Avolio A

Abstract
In this prospective study, we evaluated the effectiveness and tolerability of novel therapies against hepatitis C virus (HCV) in a cohort of PWID enrolled at our centre from April 2015 to July 2016. In this analysis, a total of 174 patients were included: 11 (6.3%) were treated with pegylated-interferon (PEG-IFN) and ribavirin (RBV) containing regimens, 163 (93.7%) with IFN-free treatments. RBV has been used in 70 patients (40.2%); 59 (33.9%) patients were in opioid substitution therapy (OST) with methadone or buprenorphine. Overall, sustained virological response (SVR) has been observed in 162 subject (93.1%), breakthrough (BT) in 3 (1.7%), relapse in 1 (0.6%), drop-out in 8 (4.6%). Treatment was interrupted for clinical conditions in 7 patients: 6 (3.4%) had hepatic decompensation and 1 died for hepatocellular carcinoma (HCC). In multivariate analysis, predictive factors of treatment failure were: albumin level below 3 g/dL (OR=7.190; 95%IC=1.236-41.837; p<0.001), MELD score >10 (OR=5.886; 95%IC=1.411-35.994; p<0.001) and years of HCV infection >20 (OR=1.286; 95%IC=0.556-9.455; p=0.016). In conclusion, treatment with DAAs was effective and well tolerated in PWID; cirrhotic subjects with MELD >10 and albumin low level showed a higher risk of developing serious adverse events and treatment failure. This article is protected by copyright. All rights reserved.

PMID: 28345206 [PubMed - as supplied by publisher]

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[Surveillance system on drug abuse: Interest of the French national OPPIDUM program of French addictovigilance network].

Tue, 03/28/2017 - 9:07am
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[Surveillance system on drug abuse: Interest of the French national OPPIDUM program of French addictovigilance network].

Therapie. 2017 Feb 22;:

Authors: Frauger E, Pochard L, Boucherie Q, Giocanti A, Chevallier C, Daveluy A, Gibaja V, Caous AS, Eiden C, Authier N, Le Boisselier R, Guerlais M, Jouanjus É, Lepelley M, Pizzoglio V, Pain S, Richard N, Micallef J, le Réseau français d’addictovigilance

Abstract
It is important to assess drug abuse liability in 'real life' using different surveillance systems. OPPIDUM ('Observation of illegal drugs and misuse of psychotropic medications') surveillance system anonymously collects information on drug abuse and dependence observed in patients recruited in specialized care centers dedicated to drug dependence. The aim of this article is to demonstrate the utility of OPPIDUM system using 2015 data. OPPIDUM is a cross-sectional survey repeated each year since 1995. In 2015, 5003 patients described the modality of use of 10,159 psychoactive drugs. Among them, 77% received an opiate maintenance treatment: 68% methadone (half of them consumed capsule form) and 27% buprenorphine (39% consumed generic form). Brand-name buprenorphine is more often injected than generic buprenorphine (10% vs. 2%) and among methadone consumers 7% of methadone capsule consumers have illegally obtained methadone (vs. 9% for syrup form). The proportion of medications among psychoactive drugs injected is important (42%), with morphine representing 21% of the total psychoactive drugs injected and buprenorphine, 16%. OPPIDUM highlighted emergent behaviors of abuse with some analgesic opioids (like tramadol, oxycodone or fentanyl), pregabalin, or quetiapine. OPPIDUM highlighted variations of drugs use regarding geographic approaches or by drug dependence care centers (like in harm reduction centers). OPPIDUM clearly demonstrated that collection of valid and useful data on drug abuse is possible, these data have an interest at regional, national and international levels.

PMID: 28343650 [PubMed - as supplied by publisher]

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Infants Born to Opioid-Dependent Women in Ontario, 2002-2014.

Tue, 03/28/2017 - 9:07am
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Infants Born to Opioid-Dependent Women in Ontario, 2002-2014.

J Obstet Gynaecol Can. 2017 Mar;39(3):157-165

Authors: Brogly SB, Turner S, Lajkosz K, Davies G, Newman A, Johnson A, Dow K

Abstract
BACKGROUND: There is a paucity of data characterizing mother-infant pairs with prenatal opioid dependence in Canada. We therefore conducted a study of relevant births in Ontario from 2002 to 2014.
METHODS: We used data from the Institute for Clinical Evaluative Sciences, the linked databases of coded population-based Ontario health services records. Differences in characteristics of opioid-dependent mother-neonate pairs and infant hospital costs by year were assessed using linear regression, and we calculated rates of preterm birth, low birth weight, birth defects, mortality, and neonatal abstinence syndrome.
RESULTS: The number of infants born to opioid-dependent women in Ontario rose from 46 in 2002 to almost 800 in 2014. Methadone was most frequently used for prenatal opioid dependence; there was little buprenorphine or buprenorphine + naloxone use. Rates of preterm birth and low birth weight were high. The proportion of neonates with neonatal abstinence syndrome (58%) was stable over the study period. The mean length of neonatal hospital stay was 13.96 days. Infant hospital costs increased from $724 774 in 2003 to $10 539 988 in 2013, and the mean cost per infant grew from $9928 to $12 917. Birth defect prevalence was 75.84/1000 live births (95% CI 68.12/1000 to 84.10/1000). The stillbirth rate was 11.39/1000 births (95% CI 8.47/1000 to 14.99/1000), and the infant mortality rate was 12.21/1000 live births (95% CI 9.16/1000 to 15.95/1000).
CONCLUSION: We observed a 16-fold increase in the number of mother-infant pairs affected by opioid dependence in Ontario over the past decade. Adverse birth outcome rates were high. Expanded services for opioid-dependent women and their children are needed.

PMID: 28343557 [PubMed - in process]

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Sciatic and femoral nerve blockade using bupivacaine alone, or in combination with dexmedetomidine or buprenorphine in cats.

Tue, 03/28/2017 - 9:07am
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Sciatic and femoral nerve blockade using bupivacaine alone, or in combination with dexmedetomidine or buprenorphine in cats.

Vet Rec. 2017 Mar 24;:

Authors: Evangelista MC, Doodnaught GM, Fantoni DT, Steagall PV

Abstract
The aim of this study was to determine the onset and offset of antinociception after sciatic (ScN) and femoral (FN) nerve blocks. Six healthy adult cats (4.8±1.3years; 4.3±0.4 kg) were included in a randomised, crossover, blinded and controlled study. Following sedation with dexmedetomidine (25 µg/kg, intramuscular), each ScN and FN injection was performed using 0.1 ml/kg of saline (CONTROL), bupivacaine (0.46 per cent, 0.46 mg/kg; BUPI), bupivacaine and dexmedetomidine (1 µg/kg; BUPI-DEX) or bupivacaine and buprenorphine (2.5 µg/kg; BUPI-BUPRE). Atipamezole (250 µg/kg) was administered after injections. Paw withdrawal thresholds (PWT) and motor blockade were evaluated before sedation and up to 24 hours. The PWT were significantly increased at half an hour in CONTROL, from two to four hours in BUPI and BUPI-DEX when compared with baseline. Motor blockade was observed between one and three hours in treatments using bupivacaine. Ability to walk was significantly impaired in BUPI at half an hour to two hours, BUPI-DEX at one to two hours and BUPI-BUPRE at two hours. Antinociception was observed in BUPI between one and eight hours, and in BUPI-DEX and BUPI-BUPRE between one and four hours. This study could not demonstrate a benefit of administering bupivacaine with dexmedetomidine or buprenorphine in cats. Results in BUPI-DEX may have been biased by the administration of atipamezole.

PMID: 28341722 [PubMed - as supplied by publisher]

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