Combatting pain after orthopedic/trauma surgery- perioperative oral extended-release tapentadol vs. extended-release oxycodone/naloxone

Abstract

BackgroundHigh post-operative pain scores after “minor” orthopedic/trauma surgery are in part attributed to inadequate prescription of opioid analgesics. Novel concepts aiming to achieve sufficient analgesia while minimizing opioid-related side effects by avoiding fluctuating plasma levels are based on perioperative oral administration of extended-release opioids beginning with the first dose pre-operatively. This is the first study to evaluate analgesic efficacy and side effect rates of extended-release tapentadol compared to oxycodone/naloxone following orthopedic/trauma surgery.MethodsThis randomized, observer-blinded, active-controlled prospective clinical trial had 2 co-primary endpoints: (1) Analgesic efficacy: Mean pain level on a numeric rating scale (NRS) from 0 to 10 during exercise over 5 days. (2) Safety: Side effect sum score of the following events: Nausea, vomiting, constipation, sedation, vertigo, somnolence. The study was powered to detect superiority of tapentadol for at least one endpoint pending statistical proof of non-inferiority for both endpoints in a first step.ResultsTwo hundred sixty-six trauma patients were randomized to receive either tapentadol (n = 133) or oxycodone/naloxone (n = 133). Analgesic efficacy: Mean (±SD) daily pain levels in the first five post-operative days were 2.8 ± 1.3 in both groups. Mean maximum pain intensity during exercise in the first 24 h after surgery was 3.8 ± 1.9 (tapentadol) and 3.8 ± 2.1 (oxycodone/naloxone). Statistically tapentadol was non-inferior but not superior to oxycodone/naloxone. Safety: Vomiting on day 1 occurred in 11%, constipation in 35% of the tapentadol patients and in 16% and 30% of the oxycodone/naloxone patients (p = 0.60 and 0.33), respectively. The incidence of sedation/ vertigo was <10%, that of somnolence <2% in both groups (p > 0.3, respectively). The sum score of side effect events was 51% in the tapentadol vs. 49% in the oxycodone/naloxone group; risk difference 3% [95% CI, −8 to 14%]; p = 0.6). Non-inferiority of tapentadol could not be concluded as the pre-defined non-inferiority margin was exceeded.ConclusionsWith both concepts, mean maximum pain intensity during exercise within the first 24 h after orthopedic/trauma surgery was reduced to a score of <4. This analgesic efficacy came at the cost of mainly gastro-intestinal side effects. Thus, we now use a prophylaxis against nausea and vomiting and pre-emptive laxatives as part of these concepts.Trial registrationhttps://eudract.ema.europa.eu (EudraCT- Nr. 2011–003238-15); October 24th, 2012.

Orthopedic Professionals’ Recognition and Knowledge of Pain and Perceived Barriers to Optimal Pain Management at Five Hospitals

“…Optimal and effective pain management necessitates knowledgeable and trained healthcare practitioners, and appropriate attitudes and assessment skills [ 14 , 20 ]. For instance, high post-operative pain scores after “minor” orthopedic/trauma surgeries were partly attributed to inadequate prescription of opioid analgesics [ 21 ]. Elderly patients comprise a special concern, as the aging process affects the doses of opioid analgesics and contributes to failure of organs [ 22 ], and among older patients, postoperative pain management is a key element related to delirium [ 23 ].…”

<p>Tapentadol: an overview of the safety profile</p>

“…Tapentadol PR and oxycodone/naloxone PR were recently compared also in the field of postoperative pain treatment in orthopedic trauma surgery by Haeseler et al34 In this randomized, observer-blinded, active-controlled prospective clinical trial, gastrointestinal AEs showed no statistically difference between the two drugs. In particularly, constipation occurred during observation in 35% of the tapentadol PR patients and in 30% of the oxycodone/naloxone PR patients while vomiting occurred in 3% of the tapentadol PR patients and in 8% of the oxycodone/naloxone PR patients.…”

<p>Tapentadol in the treatment of osteoarthritis: pharmacological rationale and clinical evidence</p>

“…The PR formulation of tapentadol in this setting has been evaluated by Haeseler et al, who conducted a randomized, observer-blinded, active-controlled (oxycodone/naloxone) trial in patients following orthopedic/trauma surgery 38. In total, 133 patients received tapentadol and an equal number oxycodone.…”