RESUMEN
Background: Opioid analgesics continue to be prescribed after ambulatory surgery despite untoward adverse effects, risk of overdose, and association with substance use disorder. Purpose/Hypothesis: The purpose was to investigate the use of a novel system to provide scheduled and simultaneous dosing of acetaminophen, celecoxib, and pregabalin after anterior cruciate ligament reconstruction (ACLR). It was hypothesized that this system would markedly reduce pain and opioid use compared with existing best practice. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Included were 100 patients scheduled for elective, primary ACLR using allograft or hamstring tendon autograft. Selection criteria included age between 18 and 65 years and weight between 65 and 120 kg. Exclusion criteria were a known allergy to any drug used in the study or the use of opioid analgesics before surgery. Patients in the intervention group received a blister pack with scheduled, simultaneous doses of acetaminophen, celecoxib, and pregabalin; patients were also given oxycodone 5 mg as needed for breakthrough pain. Patients in the control group were prescribed ibuprofen and oxycodone 5 mg/acetaminophen 325 mg as needed for pain. The primary outcome measure was pain. Secondary outcomes were nausea, itching, and daily oxycodone use. Patients were asked to quantify their average pain at rest, nausea, and itching on an 11-point verbal scale (from 0 to 10). These data were recorded for 6 days during daily telephone contacts with patients after hospital discharge. Results: Cumulative results for 6 days showed significantly lower values in the intervention group compared with the control group for pain (median [interquartile range], 28 [14-35] vs 35 [28-41], respectively; P = .009) and oxycodone use (median [interquartile range] number of tablets, 0 [0-2] vs 8 [1.25-16], respectively; P < .001). Based on these data, the upper tolerance limits for the number of oxycodone tablets required by 90% of patients in the intervention and control groups were 8 tablets and 30 tablets, respectively. Cumulative results for nausea and itching were also significantly lower for the intervention group. Most patients in the intervention group used no opioids during recovery. Conclusion: Simultaneous dosing of 3 nonopioid analgesics resulted in reduced postoperative pain and markedly lower opioid use. Registration: NCT04015908 (ClinicalTrials.gov identifier).
RESUMEN
The designer stimulant 4-methylmethcathinone (mephedrone) is among the most popular of the derivatives of the naturally occurring psychostimulant cathinone. Mephedrone has been readily available for legal purchase both online and in some stores and has been promoted by aggressive Web-based marketing. Its abuse in many countries, including the United States, is a serious public health concern. Owing largely to its recent emergence, there are no formal pharmacodynamic or pharmacokinetic studies of mephedrone. Accordingly, the purpose of this study was to evaluate effects of this agent in a rat model. Results revealed that, similar to methylenedioxymethamphetamine, methamphetamine, and methcathinone, repeated mephedrone injections (4× 10 or 25 mg/kg s.c. per injection, 2-h intervals, administered in a pattern used frequently to mimic psychostimulant "binge" treatment) cause a rapid decrease in striatal dopamine (DA) and hippocampal serotonin (5-hydroxytryptamine; 5HT) transporter function. Mephedrone also inhibited both synaptosomal DA and 5HT uptake. Like methylenedioxymethamphetamine, but unlike methamphetamine or methcathinone, repeated mephedrone administrations also caused persistent serotonergic, but not dopaminergic, deficits. However, mephedrone caused DA release from a striatal suspension approaching that of methamphetamine and was self-administered by rodents. A method was developed to assess mephedrone concentrations in rat brain and plasma, and mephedrone levels were determined 1 h after a binge treatment. These data demonstrate that mephedrone has a unique pharmacological profile with both abuse liability and neurotoxic potential.