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Cureus Mar 2024Orthopedic surgeons are the third highest prescribers of narcotics. Previous work demonstrated that surgeons prescribe three times the narcotics required, and most...
INTRODUCTION
Orthopedic surgeons are the third highest prescribers of narcotics. Previous work demonstrated that surgeons prescribe three times the narcotics required, and most patients do not properly dispose of leftover medication following surgery. This has prompted the creation of multimodal pain regimens to reduce reliance on narcotics. It is unknown if these pathways can effectively eliminate opioids following total knee arthroplasty (TKA). Our purpose was to evaluate a multimodal regimen without schedule II narcotics following TKA, in a randomized, blinded fashion. We hypothesized that there would be no difference in pain scores between groups.
METHODS
A total of 43 narcotic-naïve patients participated in a randomized, double-blinded, placebo-controlled trial. Postoperative protocols were identical between cohorts, except for the study medication. The narcotic group received an encapsulated 5 mg oxycodone, whereas the control group received an encapsulated placebo. Perioperative outcomes were compared with routine statistical analysis.
RESULTS
Four patients withdrew early secondary to pain: three in the placebo group and one in the narcotic group (p=1.00). We found no difference in hospital length of stay (p=0.09) or pain scores at all time points between cohorts (all p>0.05). There was a higher proportion of patients using a narcotic in the opioid treatment arm at day 30 (40% vs. 21.4%, p=0.29) and day 60 (20% vs. 7.1%, p=0.32), although this was not statistically significant.
CONCLUSION
A multimodal regimen without schedule II narcotics demonstrates equivalent pain scores and may reduce the risk of long-term opioid dependence following TKA.
PubMed: 38618342
DOI: 10.7759/cureus.56150 -
Journal of Chromatography. B,... May 2024Oxycodone, an opioid commonly used to treat pain in humans, has the potential to be abused in racehorses to enhance their performance. To understand the pharmacokinetics...
Oxycodone, an opioid commonly used to treat pain in humans, has the potential to be abused in racehorses to enhance their performance. To understand the pharmacokinetics of oxycodone and its metabolites in horses, as well as to detect the illegal use of oxycodone in racehorses, a method for quantification and confirmation of oxycodone and its metabolites is needed. In this study, we developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method that can simultaneously quantify and confirm oxycodone and eight metabolites in equine urine. Samples were subjected to enzymatic hydrolysis and then liquid-liquid extraction using ethyl acetate. The analyte separation was achieved on a Hypersil Gold C18 sub-2 µm column and analytes were detected on a triple quadrupole mass spectrometer. The limit of detection (LOD) and lower limit of quantification (LLOQ) were 25-50 pg/mL and 100 pg/mL, respectively. Excellent linearity of the calibration curves was observed over a range of 100-10000 pg/mL for all nine analytes. Retention time, signal-to-noise ratio, and product ion ratios were utilized as confirmation criteria, with the limits of confirmation (LOC) ranging from 100 to 250 pg/mL. The data from a pilot pharmacokinetic (PK) study suggested that oxycodone metabolites have longer detection periods in equine urine compared to oxycodone itself; thus, the detection of metabolites in equine urine extends the ability to detect oxycodone exposure in racehorses.
Topics: Animals; Horses; Tandem Mass Spectrometry; Oxycodone; Chromatography, High Pressure Liquid; Limit of Detection; Reproducibility of Results; Linear Models
PubMed: 38615430
DOI: 10.1016/j.jchromb.2024.124125 -
International Journal of Molecular... Mar 2024Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children....
Bile has emerged as an alternative matrix for toxicological investigation of drugs in suspected forensic cases of overdose in adults and intoxications in children. Toxicological investigation consists in screening and, subsequently, confirming the result with specific techniques, such as liquid chromatography with tandem mass spectrometry (LC-MS/MS). As there is no screening test on the market to test postmortem bile specimens, the novelty of this study was in investigating the applicability of a chemiluminescence immunoassay, designed for other matrices and available on the market, on bile and validate its use, testing the agreement with LC-MS/MS analysis. Bile specimens were obtained from 25 forensic cases of suspected death from overdose and intoxication. Sample preparation for bile screening consists simply in centrifugation and dilution. Confirmation analysis allows simultaneous identification of 108 drugs and was validated on bile. Kappa analysis assessed a perfect agreement (0.81-1) between the assays for benzodiazepines, methadone, opiates, cocaine, oxycodone, cannabinoids, buprenorphine and pregabalin; a substantial agreement (0.41-0.6) was reported for barbiturates. No agreement was assessed for amphetamines, due to an abundance of putrefactive amines in postmortem specimens. In conclusion, this fast and easy immunoassay could be used for initial screening of bile specimens, identifying presence of drugs, except amphetamines, with reliability.
Topics: Adult; Child; Humans; Bile; Chromatography, Liquid; Luminescence; Reproducibility of Results; Tandem Mass Spectrometry; Drug Overdose; Amphetamines
PubMed: 38612632
DOI: 10.3390/ijms25073825 -
Genes, Brain, and Behavior Apr 2024Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD....
Opioid use disorder (OUD) is an ongoing public health concern in the United States, and relatively little work has addressed how genetic background contributes to OUD. Understanding the genetic contributions to oxycodone-induced analgesia could provide insight into the early stages of OUD development. Here, we present findings from a behavioral phenotyping protocol using several inbred strains from the Hybrid Rat Diversity Panel. Our behavioral protocol included a modified "up-down" von Frey procedure to measure inherent strain differences in the sensitivity to a mechanical stimulus on the hindpaw. We also performed the tail immersion assay, which measures the latency to display tail withdrawal in response to a hot water bath. Initial withdrawal thresholds were taken in drug-naïve animals to record baseline thermal sensitivity across the strains. Oxycodone-induced analgesia was measured after administration of oxycodone over the course of 2 h. Both mechanical and thermal sensitivity are shaped by genetic factors and display moderate heritability (h = 0.23-0.40). All strains displayed oxycodone-induced analgesia that peaked at 15-30 min and returned to baseline by 2 h. There were significant differences between the strains in the magnitude and duration of their analgesic response to oxycodone, although the heritability estimates were quite modest (h = 0.10-0.15). These data demonstrate that genetic background confers differences in mechanical sensitivity, thermal sensitivity, and oxycodone-induced analgesia.
Topics: Rats; Animals; Oxycodone; Analgesics, Opioid; Analgesia; Opioid-Related Disorders
PubMed: 38597363
DOI: 10.1111/gbb.12894 -
Archives of Plastic Surgery Mar 2024Perioperative management in autologous breast reconstruction has gained focus in recent years. This study compares two pain management protocols in patients...
Comparison of Pain Management Strategies to Reduce Opioid Use Postoperatively in Free Flap Breast Reconstruction: Pain Catheter versus Nerve Block in Addition to Refinements in the Oral Pain Management Regime.
Perioperative management in autologous breast reconstruction has gained focus in recent years. This study compares two pain management protocols in patients undergoing abdominal-based free flap breast reconstruction: a past protocol (PP) and a current protocol (CP)-both intended to reduce opioid consumption postoperatively. The PP entails use of a pain catheter in the abdominal wound and the CP consists of an intraoperative nerve block in addition to refinements in the oral pain management. We hypothesize that the CP reduces opioid consumption compared to PP. From December 2017 to January 2020, 102 patients underwent breast reconstruction with an abdominal-based free flap. Two postoperative pain management strategies were used during the period; from December 2017 to September 2018, the PP was used which entailed the use of a pain catheter with ropivacaine applied in the abdominal wound with continuous distribution postoperatively in addition to paracetamol orally and oxycodone orally pro re nata (PRN). From October 2018 to January 2020, the CP was used. This protocol included a combination of intraoperative subfascial nerve block and a postoperative oral pain management regime that consisted of paracetamol, celecoxib, and gabapentin as well as oxycodone PRN. The CP group ( = 63) had lower opioid consumption compared to the PP group ( = 39) when examining all aspects of opioid consumption, including daily opioid usage in morphine milligram equivalents and total opioid usage during the stay ( < 0.001). The CP group had shorter length of hospital stay (LOS). Introduction of the CP reduced opioid use and LOS was shorter.
PubMed: 38596158
DOI: 10.1055/s-0043-1777673 -
Biomedical Chromatography : BMC Jul 2024A sensitive and reliable LC-MS/MS method was developed and validated for the quantification of oxycodone and metabolites in human plasma. The method has a runtime of...
A rapid and sensitive LC-MS/MS method for quantifying oxycodone, noroxycodone, oxymorphone and noroxymorphone in human plasma to support pharmacokinetic drug interaction studies of oxycodone.
A sensitive and reliable LC-MS/MS method was developed and validated for the quantification of oxycodone and metabolites in human plasma. The method has a runtime of 6 min and a sensitivity of 0.1 μg/L for all analytes. Sample preparation consisted of protein precipitation. Separation was performed on a Kinetix biphenyl column (2.1 × 100 mm, 1.7 μm), using ammonium formate 5 mm in 0.1% aqueous formic acid and methanol LC-MS grade 100% in gradient elution at a flow rate of 0.4 ml/min. Detection was performed in multiple reaction monitoring mode using positive electrospray ionization. The method was linear over the calibration range of 0.1-25.0 μg/L for oxycodone, noroxycodone and noroxymorphone and 0.1-5.0 μg/L for oxymorphone. The method demonstrated good performance in terms of intra- and interday accuracy (86.5-110.3%) and precision (CV 1.7-9.3%). The criteria for the matrix effect were met (CV < 15%) except for noroxymorphone, for which an additional method was applied to compensate for the matrix effect. Whole blood samples were stable for 4 h at room temperature. Plasma samples were stable for 24 h at room temperature and 3 months at -20°C. Furthermore, the method was successfully applied in a pharmacokinetic drug interaction study of oxycodone and enzalutamide in patients with prostate cancer.
Topics: Humans; Tandem Mass Spectrometry; Oxycodone; Reproducibility of Results; Chromatography, Liquid; Linear Models; Drug Interactions; Male; Morphinans; Limit of Detection; Oxymorphone; Sensitivity and Specificity; Drug Stability; Liquid Chromatography-Mass Spectrometry
PubMed: 38587098
DOI: 10.1002/bmc.5874 -
Annals of Palliative Medicine Mar 2024Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important...
BACKGROUND
Many of the drugs used for the treatment and alleviation of symptoms in cancer patients are known to inhibit or induce cytochrome P450 (CYP). Therefore, it is important to pay attention to the drug interactions of opioid analgesics that are metabolized by CYPs, because for example when using oxycodone metabolized by CYP3A4, it is possible that the effect will be attenuated or enhanced by the concomitant use of drugs that induce or inhibit CYP3A4. Aprepitant, an antiemetic drug used in many patients receiving anticancer drugs, is known as a moderate competitive inhibitor of CYP3A4. We experienced a case of respiratory depression caused by opioids, which was suspected to be caused by a drug interaction with antiemetics especially aprepitant.
CASE DESCRIPTION
The patient was a 72-year-old man. He had been treated with continuous oxycodone infusion for perianal pain associated with the rectal invasion of prostate cancer. No comorbidities other than renal dysfunction were observed. Oxycodone treatment was started at 48 mg/day, and was increased to 108 mg/day, and then the pain decreased. Once the pain was controlled, chemotherapy was planned. Antiemetics (dexamethasone, palonosetron, and aprepitant) were administered before anticancer drug administration. Approximately 3 hours after antiemetics administration and before the administration of the anticancer drugs, a ward nurse noticed that oversedation and respiratory depression had occurred. When the patient was called, he immediately woke up and was able to talk normally, so the anticancer drugs were administered as scheduled. About 2 hours after the nurse noticed oversedation, the attending physician reduced the dose of oxycodone infusion to 48 mg/day. After that, his drowsiness persisted, but his respiratory condition improved. Despite reducing the dose of oxycodone to less than half, the pain remained stable at numeric rating scale (NRS) 0-1, without the use of a rescue dose. The patient was discharged from the hospital 36 days after the administration of anticancer drugs, without any problems.
CONCLUSIONS
The cause of respiratory depression in this case was thought to be a combination of factors, including drug interactions between oxycodone and antiemetics, and oxycodone accumulation due to renal dysfunction.
Topics: Male; Humans; Aged; Antiemetics; Aprepitant; Analgesics, Opioid; Oxycodone; Cytochrome P-450 CYP3A; Morpholines; Antineoplastic Agents; Drug Interactions; Prostatic Neoplasms; Pain; Respiratory Insufficiency; Kidney Diseases
PubMed: 38584476
DOI: 10.21037/apm-23-581 -
European Journal of Pain (London,... Apr 2024Although opioids are a mainstay for perioperative pain management in hip fracture patients, no studies have described changes in opioid use over the last two decades....
BACKGROUND
Although opioids are a mainstay for perioperative pain management in hip fracture patients, no studies have described changes in opioid use over the last two decades. The aim of this study was to describe time trends in opioid use in a population-based cohort of patients undergoing a first-time hip fracture surgery during 1997-2018.
METHODS
Opioid-naïve hip fracture patients >55 years old were identified in Danish medical databases (n = 115,962). By 2-year calendar periods, we calculated prevalence rates (PR) of opioid use in the four quarters after surgery (Q1-Q4). Corresponding prevalence rate ratios (PRR) with 1997-1998 as a reference were estimated with 95% confidence intervals. Further, we calculated the median morphine milligram equivalents (MME) for each quarter.
RESULTS
For Q1, the PR of opioid use increased from 29% in 1997-1998 to 78% in 2017-2018 corresponding to a PRR of 2.7 (2.6-2.8). For Q4, the PR was 15% in 1997-1998, peaked in 2003-2004 and then decreased, but stayed high at 13% in 2017-2018. The median MME did not increase when comparing 2017-2018 with 1997-1998, irrespective of the quarter. Tramadol was most frequently used in 1997-1998 shifting to oxycodone in 2017-2018.
CONCLUSION
The PRs of opioid use in Q1 after surgery increased substantially from 1997 to 2018, but this did not translate into increased opioid use up to 1 year after hip fracture surgery or higher dosage. Our findings underline the importance of sustained focus on opioid tapering, dosage and use of opioids with the lowest potential for addiction and other adverse events.
SIGNIFICANCE STATEMENT
Overall, opioid use in Q1 after hip fracture surgery increased 2.7 times from 1997 to 2018, but the doses and opioid use up to 1 year after surgery remained stable. Compared to elderly, younger patients were more likely to use opioid in Q1, while the tendency was opposite in Q2-Q4. The most used opioid type changed from tramadol to oxycodone. Our findings underline the importance of personalized opioid tapering and doses, and use of opioids with the lowest potential for addiction and other adverse events.
PubMed: 38581227
DOI: 10.1002/ejp.2271 -
BMC Geriatrics Apr 2024Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex...
BACKGROUND
Tramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA.
METHODS
This retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models.
RESULTS
The study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons.
CONCLUSIONS
Postoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.
Topics: Humans; Aged; United States; Analgesics, Opioid; Tramadol; Oxycodone; Arthroplasty, Replacement, Knee; Hydrocodone; Retrospective Studies; Arthroplasty, Replacement, Hip; Medicare
PubMed: 38580920
DOI: 10.1186/s12877-024-04933-2 -
British Journal of Clinical Pharmacology Jul 2024Oxycodone is the most commonly prescribed strong opioid in Australia. This study describes health service antecedents and sociodemographic factors associated with...
AIMS
Oxycodone is the most commonly prescribed strong opioid in Australia. This study describes health service antecedents and sociodemographic factors associated with oxycodone initiation.
METHODS
Population-based new user cohort study linking medicine dispensings, hospitalizations, emergency department visits, medical services and cancer notifications from New South Wales (NSW) for 2014-2018. New users had no dispensings of any opioid in the preceding year. We analysed health service use in the 5 days preceding initiation and proportion of people on treatment over 1 year and fitted an area-based, multivariable initiation model with sociodemographic covariates.
RESULTS
Oxycodone accounted for 30% of opioid initiations. Annually, 3% of the NSW population initiated oxycodone, and 5-6% were prevalent users; the new user cohort comprised 830 963 people. Discharge from hospital (39.3%), therapeutic procedures (21.4%) and emergency department visits (19.7%) were common; a hospital admission for injury (6.0%) or a past-year history of cancer (7.2%) were less common. At 1 year after initiation, 4.6% of people were using oxycodone. In the multivariable model, new use of oxycodone increased with age and was higher for people outside major cities, for example, an incidence rate ratio of 1.43 (95% confidence interval 1.36-1.51) for inner regional areas relative to major cities; there was no evidence of variation in rates of new use by social disadvantage.
CONCLUSION
About half of new oxycodone use in NSW was preceded by a recent episode of hospital care or a therapeutic procedure. Higher rates of oxycodone initiation in rural and regional areas were not explained by sociodemographic factors.
Topics: Humans; Oxycodone; Male; Female; Middle Aged; Adult; Analgesics, Opioid; New South Wales; Aged; Adolescent; Young Adult; Hospitalization; Emergency Service, Hospital; Sociodemographic Factors; Cohort Studies; Child; Aged, 80 and over; Child, Preschool; Infant
PubMed: 38571341
DOI: 10.1111/bcp.16063