Antinociception by Spinal and Systemic Oxycodone: Why Does the Route Make a Difference?

Background The pharmacology of oxycodone is poorly understood despite its growing clinical use. The discrepancy between its good clinical effectiveness after systemic administration and the loss of potency after spinal administration led the authors to study the pharmacodynamic effects of oxycodone and its metabolites using in vivo and in vitro models in rats. Methods Male Sprague-Dawley rats were used in hot-plate, tail-flick, and paw-pressure tests to study the antinociceptive properties of morphine, oxycodone, and its metabolites oxymorphone and noroxycodone. Mu-opioid receptor agonist-stimulated GTPgamma[S] autoradiography was used to study G-protein activation induced by morphine, oxycodone, and oxymorphone in the rat brain and spinal cord. Spontaneous locomotor activity was measured to assess possible sedation or motor dysfunction. Naloxone and the selective kappa-opioid receptor antagonist nor-binaltorphimine were used to study the opioid receptor selectivity of the drugs. Results Oxycodone showed lower efficacy and potency to stimulate GTPgamma[S] binding in the spinal cord and periaqueductal gray compared with morphine and oxymorphone. This could relate to the fact that oxycodone produced only weak naloxone-reversible antinociception after intrathecal administration. It also suggests that the metabolites may have a role in oxycodone-induced analgesia in rats. Intrathecal oxymorphone produced strong long-lasting antinociception, whereas noroxycodone produced antinociception with very high doses only. Subcutaneous administration of oxycodone and oxymorphone produced thermal and mechanical antinociception that was reversed by naloxone but not by nor-binaltorphimine. Oxymorphone was more potent than oxycodone, particularly in the hot-plate and paw-pressure tests. Conclusions The low intrathecal potency of oxycodone in rats seems be related to its low efficacy and potency to stimulate mu-opioid receptor activation in the spinal cord

Outcome and patients' satisfaction after functional treatment of acute lateral ankle injuries at emergency departments versus family doctor offices

<p>Abstract</p> <p>Background</p> <p>In some Western countries, more and more patients seek initial treatment even for minor injuries at emergency units of hospitals. The initial evaluation and treatment as well as aftercare of these patients require large amounts of personnel and logistical resources, which are limited and costly, especially if compared to treatment by a general practitioner. In this study, we investigated whether outsourcing from our level 1 trauma center to a general practitioner has an influence on patient satisfaction and compliance.</p> <p>Methods</p> <p>This prospective, randomized study, included n = 100 patients who suffered from a lateral ankle ligament injury grade I-II (16, 17). After radiological exclusion of osseous lesions, the patients received early functional treatment and were shown physical therapy exercises to be done at home, without immobilization or the use of stabilizing ortheses. The patients were randomly assigned into two groups of 50 patients each: Group A (ER): Follow-up and final examination in the hospital's emergency unit. Group B (GP): Follow-up by general practitioner, final examination at hospital's emergency unit. The patients were surveyed regarding their satisfaction with the treatment and outcome of the treatment.</p> <p>Results</p> <p>Female and male patients were equally represented in both groups. The age of the patients ranged from 16 – 64 years, with a mean age of 34 years (ER) and 35 years (GP). 98% (n = 98) of all patients were satisfied with their treatment, and 93% (n = 93) were satisfied with the outcome. For these parameters no significant difference between the two groups could be noted (p = 0.7406 and 0.7631 respectively). 39% of all patients acquired stabilizing ortheses like ankle braces (Aircast, Malleoloc etc.) on their own initiative. There was a not significant tendency for more self-acquired ortheses in the group treated by general practicioners (p = 0,2669).</p> <p>Conclusion</p> <p>Patients who first present at the ER with a lateral ankle ligament injury grade I-II can be referred to a general practitioner for follow-up treatment without affecting patient satisfaction regarding treatment and treatment outcome.</p

Meta-analysis of randomised clinical trials comparing open and laparoscopic anti-reflux surgery

Objective: The aim was to conduct a meta-analysis of the randomised evidence to determine the relative merits of laparoscopic anti-reflux surgery (LARS) and open anti-reflux surgery (OARS) for proven gastro-oesophageal reflux disease. Methodology: A search of the Medline, Embase, Science Citation Index, Current Contents and PubMed databases identified all randomised clinical trials that compared LARS and OARS and were published in the English language between 1990 and 2007. The meta-analysis was prepared in accordance with the Quality of Reporting of Meta-analyses (QUOROM) statement. The six outcome variables analysed were operating time, hospital stay, return to normal activity, perioperative complications, treatment failure and requirement for further surgery. Random effects meta-analyses were performed using odds ratios and weighted mean differences. Results: Twelve trials were considered suitable for the meta-analysis. A total of 503 patients underwent OARS and 533 had LARS. For three of the six outcomes the summary point estimates favoured LARS over OARS. There was a significant reduction of 2.68 days in the duration of hospital stay for the LARS group compared with the OARS group (WMD -2.68, 95% confidence interval (CI) -3.54 to -1.81; P < 0.0001), a significant reduction of 7.75 days in return to normal activity for the LARS group compared with the OARS group (WMD -7.75, 95% CI -14.37 to -1.14; P = 0.0216) and lastly there was a statistically significant reduction of 65% in the relative odds of complication rates for the LARS group compared with the OARS group (OR 0.35, 95% CI 0.16 to 0.75; P = 0.0072). Duration of operating time was significantly longer (39.02 minutes) in the LARS group (WMD 39.02, 95% CI 17.99 to 60.05; P = 0.0003). Treatment failure rates were comparable between the two groups (OR 1.39, 95% CI 0.71 to 2.72; P = 0.3423). Despite this the requirement for further surgery was significantly higher in the LARS group (OR 1.79, 95% CI 1.00 to 3.22; P = 0.05). Conclusions: Based on this meta-analysis, the authors conclude that LARS is an effective and safe alternative to OARS for the treatment of proven gastro-oesophageal reflux disease. LARS enables a faster convalescence and return to productive activity, with a reduced risk of complications and a similar treatment outcome to that of an open approach. However, there is a significantly higher rate of re-operation (79%) in the LARS group

Population-based trend analysis of laparoscopic Nissen and Toupet fundoplications for gastroesophageal reflux disease

The Nissen and Toupet fundoplications are the most commonly used techniques for surgical treatment of gastroesophageal reflux disease. To date, no population-based trend analysis has been reported examining the choice of procedure and short-term outcomes. This study was designed to analyze trends in the use of Nissen versus Toupet fundoplications, and corresponding short-term outcomes during a 10-year period between 1995 and 2004