-
Surgery in Practice and Science Dec 2023Surgeon-prescribed opioids contribute to 11% of prescription drug overdoses in the United States (US). With prescription opioids involved in 24% of all opioid-related...
BACKGROUND
Surgeon-prescribed opioids contribute to 11% of prescription drug overdoses in the United States (US). With prescription opioids involved in 24% of all opioid-related overdose deaths in 2020, the US Centers for Disease Control and Prevention (CDC) recommends naloxone co-prescribing to patients at high-risk of overdose and death as a harm reduction strategy. We sought to 1) examine naloxone co-prescribing rates to surgical patients (using common post-surgical prescribing amounts) and those with potential risk factors for opioid-related overdoses or adverse events, and 2) identify the factors associated with patients receiving naloxone co-prescriptions.
METHODS
We conducted a single-institution, retrospective study using the electronic medical records of all patients undergoing surgery at an academic institution between August 2020 and May 2021. We included post-surgical adults prescribed opioids that were sent to a pharmacy in our health system. The primary outcome was the percentage of co-prescribed naloxone in patients prescribed opioids.
RESULTS
The overall naloxone co-prescription rate was low (1.7%). Only 14.6% of patients prescribed ≥350 morphine milligram equivalents (MME, equivalent to 46.7 oxycodone 5 mg tablets) and 8.6% of patients using illicit drugs were co-prescribed naloxone. On multivariable analysis, patients who were prescribed >350 MME, used illicit drugs or tobacco, underwent an elective or emergent general surgery procedure, self-identified as Hispanic, or had ASA scores of 2-4 were more likely to receive a naloxone co-prescription.
CONCLUSIONS
Naloxone co-prescribing after surgery remains low, even for high-risk patients. Harm reduction strategies such as naloxone, safe storage, and disposal of leftover opioids could reduce surgeons' iatrogenic contributions to the worsening US opioid crisis.
PubMed: 38222465
DOI: 10.1016/j.sipas.2023.100217 -
European Journal of Clinical... Mar 2024Oxycodone is known to have numerous drug-drug interactions (DDIs) that can potentially decrease efficacy or lead to adverse drug reactions (ADRs). However, there is...
AIM
Oxycodone is known to have numerous drug-drug interactions (DDIs) that can potentially decrease efficacy or lead to adverse drug reactions (ADRs). However, there is limited research on the frequency of DDIs associated with oxycodone, which is important in optimising pharmacovigilance and the need for additional research on certain DDIs. In this study, the frequency of pharmacologically and clinically relevant DDI perpetrators was studied in patients with cancer.
METHODS
This was a cross-sectional study using hospital pharmacy records of patients with cancer who were prescribed oxycodone between September 2021 and September 2022. Medication records of patients prescribed oxycodone during a period of ≥ 5 consecutive days (= oxycodone treatment episodes) were reviewed to identify the concomitant use of pharmacologically relevant perpetrators, based on reference sources (Lexicomp®, Micromedex®, the Dutch Kennisbank and the Dutch Commentaren Medicatiebewaking). The clinical relevance was examined by a clinical pharmacologist and a medical oncologist. Additionally, the frequency of double interactions-concomitant oxycodone use with two CYP3A4 and / or CYP2D6 perpetrators-was studied.
RESULTS
Overall, 254 oxycodone treatment episodes were included, of which 227 (89.4%) were found to contain at least one pharmacologically relevant DDI perpetrator. Of these, 210 (82.7%) were considered to be clinically relevant. A total of 80 different pharmacologically relevant perpetrators were identified, with 65 (81.3%) being considered clinically relevant. Double interactions were observed in 21 (8.3%) oxycodone treatment episodes.
CONCLUSION
A high frequency of pharmacologically and clinically relevant perpetrators of oxycodone was observed in our cohort. Moreover, a high number of double interactions involving oxycodone was registered. More intense monitoring of DDIs may be needed to improve medication safety of patients with cancer taking oxycodone.
Topics: Humans; Oxycodone; Cross-Sectional Studies; Clinical Relevance; Drug Interactions; Neoplasms
PubMed: 38217692
DOI: 10.1007/s00228-023-03612-2 -
Journal of Clinical Medicine Dec 2023Opioids are used in pharmacotherapy for chronic pain. The phenomenon of their influence on the oxidative-antioxidant balance is poorly understood. Additionally, little...
BACKGROUND
Opioids are used in pharmacotherapy for chronic pain. The phenomenon of their influence on the oxidative-antioxidant balance is poorly understood. Additionally, little is known about the oxidative status in patients receiving chronic opioid noncancer pain therapy.
METHODS
The primary goal was to explore oxidative status using the total oxidative capacity (TOC) and total antioxidative capacity (TAC) in patients with chronic lower back pain (LBP) treated with opioids. The secondary task was to present the risk factors connected with the duration of therapy or anthropometric parameters. Plasma TOC and TAC were analyzed in the study group (n = 28), i.e., patients with chronic LBP treated with opioids, and in the control group (n = 11), i.e., healthy volunteers.
RESULTS
The TAC was significantly lower in the study group compared to the control group ( < 0.05), while the TOC did not differ significantly. A statistically lower TOC for buprenorphine compared to oxycodone ( = 0.019) and tramadol ( = 0.036) was observed. The TOC did not differ between tramadol and oxycodone. The highest TAC was described for oxycodone, while the TAC for buprenorphine and tramadol was significantly lower in comparison with oxycodone ( = 0.007 and = 0.016). The TOC/TAC ratio was higher in patients with nicotinism in both groups.
CONCLUSIONS
Patients receiving chronic opioid therapy presented a lower antioxidative capacity. There were differences in opioid-induced oxidative imbalance, which is very important clinically. Nicotinism increases the oxidative-antioxidative imbalance. The least oxidative capacity was associated with buprenorphine, while oxycodone showed the greatest antioxidant activity. The most favorable TOC/TAC ratio was observed for buprenorphine. It is suggested that buprenorphine or oxycodone has the best profile, and there is no correlation with the duration of opioid therapy or the opioid dose. However, all opioid substances can potentially enhance the oxidative-antioxidative status.
PubMed: 38202088
DOI: 10.3390/jcm13010082 -
BMC Chemistry Jan 2024A green, efficient, sensitive and accurate detection method by HPLC-DAD and LC-MS/MS was developed and validated for the quantification of morphine, hydromorphone,...
A green, efficient, sensitive and accurate detection method by HPLC-DAD and LC-MS/MS was developed and validated for the quantification of morphine, hydromorphone, oxycodone, ketamine tramadol, dezocine, ropivacaine, remifentanil, butorphanol, bupivacaine, droperidol, fentanyl, lornoxicam and sufentanil. The 14 mixtures were chromatographed via HPLC-DAD method which employed 0.05 mol/L potassium dihydrogen phosphate solution-acetonitrile as the mobile phase, the analytes were gradient elution on a SinoChrom ODS-BP C column with a total separation time of 35 min, and 14 mixtures showed a good linear relationship in the linear range. The Limit of Quantitation (LOQ) ranged from 0.10 to 20.0 µg/mL, the inter-day and intra-day precision of each analyte is within 1.1-2.0% and 0.4-1.3%, and the average absolute recovery of all compounds was above 98%. The LC-MS/MS method was used to successfully separate the 14 mixtures within 10 min which employed 0.1% formic acid-acetonitrile as the mobile phase, the analytes were gradient elution on a ACQUITY UPLC-BEH C column with a total separation time of 13 min, and 14 mixtures showed a good linear relationship in the linear range. The LOQ ranged from 0.005 to 0.2 ng/mL, the inter-day and intra-day precision of each analyte is within 1.2-4.1% and 0.6-3.3%, and the average absolute recovery of all compounds was above 93%. The proposed method has been successfully applied in the clinic and provides a strong technical basis for the quantitative detection of these 14 mixtures for detecting drug abuse, and for studying the stability and compatibility of analgesic solutions. The proposed methods were validated against ICH guidelines.
PubMed: 38200560
DOI: 10.1186/s13065-024-01113-6 -
European Journal of Pharmaceutical... Mar 2024The concomitant administration of ritonavir and oxycodone may significantly increase the plasma concentrations of oxycodone. This study was aimed to simulate DDI between...
The concomitant administration of ritonavir and oxycodone may significantly increase the plasma concentrations of oxycodone. This study was aimed to simulate DDI between ritonavir and oxycodone, a widely used opioid, and to formulate dosing protocols for oxycodone by using physiologically based pharmacokinetic (PBPK) modeling. We developed a ritonavir PBPK model incorporating induction and competitive and time-dependent inhibition of CYP3A4 and competitive inhibition of CYP2D6. The ritonavir model was evaluated with observed clinical pharmacokinetic data and validated for its CYP3A4 inhibition potency. We then used the model to simulate drug interactions between oxycodone and ritonavir under various dosing scenarios. The developed model captured the pharmacokinetic characteristics of ritonavir from clinical studies. The model also accurately predicts exposure changes of midazolam, triazolam, and oxycodone in the presence of ritonavir. According to model simulations, the steady-state maximum, minimum and average concentrations of oxycodone increased by up to 166% after co-administration with ritonavir, and the total exposure increased by approximately 120%. To achieve similar steady-state concentrations, halving the dose with an unchanged dosing interval or doubling the dosing interval with an unaltered single dose should be practical for oxycodone, whether formulated in uncoated or controlled-release tablets during long-term co-medication with ritonavir. The results revealed exposure-related risks of oxycodone-ritonavir interactions that have not been studied clinically and emphasized PBPK as a workable method to direct judicious dosage.
Topics: Ritonavir; Oxycodone; Cytochrome P-450 CYP3A; Midazolam; Drug Interactions; Models, Biological
PubMed: 38199444
DOI: 10.1016/j.ejps.2024.106697 -
Pain Medicine (Malden, Mass.) Apr 2024To identify common opioid tapering trajectories among patients commencing opioid taper from long-term opioid therapy for chronic non-cancer pain and to examine...
OBJECTIVE
To identify common opioid tapering trajectories among patients commencing opioid taper from long-term opioid therapy for chronic non-cancer pain and to examine patient-level characteristics associated with these different trajectories.
DESIGN
A retrospective cohort study.
SETTING
Australian primary care.
SUBJECTS
Patients prescribed opioid analgesics between 2015 and 2020.
METHODS
Group-based trajectory modeling and multinomial logistic regression analysis were conducted to determine tapering trajectories and to examine demographic and clinical factors associated with the different trajectories.
RESULTS
A total of 3369 patients commenced a taper from long-term opioid therapy. Six distinct opioid tapering trajectories were identified: low dose / completed taper (12.9%), medium dose / faster taper (12.2%), medium dose / gradual taper (6.5%), low dose / noncompleted taper (21.3%), medium dose / noncompleted taper (30.4%), and high dose / noncompleted taper (16.7%). A completed tapering trajectory from a high opioid dose was not identified. Among patients prescribed medium opioid doses, those who completed their taper were more likely to have higher geographically derived socioeconomic status (relative risk ratio [RRR], 1.067; 95% confidence interval [CI], 1.001-1.137) and less likely to have sleep disorders (RRR, 0.661; 95% CI, 0.463-0.945) than were those who didn't complete their taper. Patients who didn't complete their taper were more likely to be prescribed strong opioids (eg, morphine, oxycodone), regardless of whether they were tapered from low (RRR, 1.444; 95% CI, 1.138-1.831) or high (RRR, 1.344; 95% CI, 1.027-1.760) doses.
CONCLUSIONS
Those prescribed strong opioids and high doses appear to be less likely to complete tapering. Further studies are needed to evaluate the clinical outcomes associated with the identified trajectories.
Topics: Humans; Analgesics, Opioid; Chronic Pain; Retrospective Studies; Australia; Prescriptions
PubMed: 38191211
DOI: 10.1093/pm/pnae002 -
Cureus Sep 2023In the United States, the rate of opioid use increases each year. With this, users are engaging in more non-traditional methods of usage. "Chasing the dragon" is a term...
In the United States, the rate of opioid use increases each year. With this, users are engaging in more non-traditional methods of usage. "Chasing the dragon" is a term used to describe opioid inhalation, where the user heats the opioid and then inhales the smoke. While this method of usage is typically associated with a quicker high and fewer adverse effects, it can also lead to toxic leukoencephalopathy (TLE). TLE is defined as a structural alteration of the brain's white matter due to toxic exposure, such as heroin. A 57-year-old woman with a history of polysubstance abuse was admitted to the hospital after weeks of erratic behavior. At presentation, her urine drug screen was found to be positive for oxycodone (which was prescribed to her) and fentanyl. A brain MRI was eventually done, which showed a periventricular leukoencephalopathy characteristic of opioid inhalation. Traditionally, opioid-related TLE is due to heroin, and patients are found to have very dramatic motor issues. As this patient did not report a history of heroin use and did not present with significant motor deficits, this report highlights the need to maintain a level of suspicion for TLE. As levels of opioid use continue to rise, it is likely that many presentations like that of the patient outlined in this report will be seen.
PubMed: 38188695
DOI: 10.7759/cureus.45774 -
Frontiers in Surgery 2023Postoperative pulmonary complications (PPCs) are common in gastric cancer patients after gastrectomy. The aim of our study was to investigate the perioperative risk...
BACKGROUND
Postoperative pulmonary complications (PPCs) are common in gastric cancer patients after gastrectomy. The aim of our study was to investigate the perioperative risk factors and to develop a nomogram to identify patients who are at significant risk of PPCs.
METHODS
The clinical data of gastric cancer patients who underwent elective gastrectomy in the First Affiliated Hospital of Nanjing Medical University from 2017 to 2021 were retrospectively collected. All patients were randomly divided into a training and a validation cohort at a ratio of 7:3. Univariate and multivariate analysis were applied to identify the independent risk factors that might predict PPCs, and a nomogram was constructed. Both discrimination and calibration abilities were estimated by the area under a receiver operating characteristic curve (AUC) and calibration curves. The clinical effectiveness of the nomogram was further quantified with the decision curve analysis (DCA).
RESULTS
Of 2,124 included patients, one hundred and fifty patients (7.1%) developed PPCs. Binary logistic analysis showed that age > 65 years, higher total cholesterol level, longer duration of surgery, total gastrectomy, and the dose of oxycodone > 5.5 mg were independent risk factors for the occurrence of PPCs, which were contained in the nomogram. The predictive nomogram showed good discrimination and calibration [an AUC of 0.735 (95% CI: 0.687-0.783) in a training cohort and 0.781 (95% CI: 0.715-0.847) in a validation cohort]. The calibration curve and decision curve analysis showed a good agreement between nomogram predictions and actual observations.
CONCLUSION
We developed a nomogram model based on age, total cholesterol, extent of resection, duration of surgery, and the dose of oxycodone to predict the risk of PPCs in gastric cancer patients after elective gastrectomy.
PubMed: 38186389
DOI: 10.3389/fsurg.2023.1308591 -
Substance Abuse Treatment, Prevention,... Jan 2024The 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in...
Comparing the effects of decreasing prescription opioid shipments and the release of an abuse deterrent OxyContin formulation on opioid overdose fatalities in WV: an interrupted time series study.
INTRODUCTION
The 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in prescription drug misuse and the associated increasing illicit opioid use and overdose rates. However, studies of this topic often do not account for changes in supplies of other prescription opioids that were widely prescribed before and after the ADF OxyContin release, including generic oxycodone formulations and hydrocodone. We therefore sought to compare the impact of the ADF OxyContin release to that of decreasing prescription opioid supplies in West Virginia (WV).
METHODS
Opioid tablet shipment and overdose data were extracted from The Washington Post ARCOS (2006-2014) and the WV Forensic Drug Database (2005-2020), respectively. Locally estimated scatterplot smoothing (LOESS) was used to estimate the point when shipments of prescription opioids to WV began decreasing, measured via dosage units and morphine milligram equivalents (MMEs). Interrupted time series analysis (ITSA) was used to compare the impact LOESS-identified prescription supply changes and the ADF OxyContin release had on prescription (oxycodone and hydrocodone) and illicit (heroin, fentanyl, and fentanyl analogues) opioid overdose deaths in WV. Model fit was compared using Akaike Information Criteria (AIC).
RESULTS
The majority of opioid tablets shipped to WV from 2006 to 2014 were generic oxycodone or hydrocodone, not OxyContin. After accounting for a 6-month lag from ITSA models using the LOESS-identified change in prescription opioid shipments measured via dosage units (2011 Q3) resulted in the lowest AIC for both prescription (AIC = -188.6) and illicit opioid-involved overdoses (AIC = -189.4), indicating this intervention start date resulted in the preferred model. The second lowest AIC was for models using the ADF OxyContin release as an intervention start date.
DISCUSSION
We found that illicit opioid overdoses in WV began increasing closer to when prescription opioid shipments to the state began decreasing, not when the ADF OxyContin release occurred. Similarly, the majority of opioid tablets shipped to the state for 2006-2014 were generic oxycodone or hydrocodone. This may indicate that diminishing prescription supplies had a larger impact on opioid overdose patterns than the ADF OxyContin release in WV.
Topics: Humans; Analgesics, Opioid; Oxycodone; Opiate Overdose; Interrupted Time Series Analysis; Hydrocodone; West Virginia; Drug Overdose; Prescriptions; Fentanyl
PubMed: 38178238
DOI: 10.1186/s13011-023-00587-2 -
BMC Anesthesiology Jan 2024Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain.... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy of postoperative analgesia with intravenous paracetamol and mannitol injection, combined with thoracic paravertebral nerve block in post video-assisted thoracoscopic surgery pain: a prospective, randomized, double-blind controlled trial.
BACKGROUND
Although video-assisted thoracoscopic surgery (VATS) has advantages of reduced injury and faster healing, patients still endure moderate and severe postoperative pain. Paracetamol and mannitol injection, the first acetaminophen injection in China, has the advantages of convenient administration, rapid onset of action, and no first-pass effect. This aim of this study was to investigate the efficacy of postoperative analgesia with paracetamol and mannitol injection, combined with thoracic paravertebral nerve block (TPVB) in post VATS pain.
METHODS
This study was a single-center, prospective, randomized, double-blind controlled clinical trial. Patients scheduled for VATS were randomly divided into three groups, general anesthesia group (Group C), TPVB group (Group T) and TPVB + paracetamol and mannitol injection group (Group TP). In this study, the primary outcome was determined as visual analog scale (VAS) scores at rest and coughing, the secondary observation outcomes were the first time to use analgesic pump, the total consumption of oxycodone in the analgesic pump, number of effective and total analgesic pump compressions at first 48 h postoperatively, the perioperative consumption of sufentanil, time to extubation, hospital length of stay, urine volume, and the incidence of adverse events.
RESULTS
In a state of rest and cough, patients in the Group TP showed significantly lower VAS pain scores at 1, 12, 24, and 48 postoperative-hour compared with Group C and Group T. Intraoperative sufentanil and postoperative oxycodone consumption, the first time to press analgesic pump, the times of effective and total compressions of patient- controlled analgesia (PCA) were lower than those of the Group C and Group T. Interestingly, urine output was higher in Group TP. There were no differences between the three groups in terms of extubation time, length of hospital stay and adverse effects, indicating that intravenous paracetamol and mannitol injection is an effective and safe perioperative analgesia method.
CONCLUSIONS
Paracetamol and mannitol injection, combined with TPVB may provide important beneficial effects on acute pain control and reduce the consumption of opioid in patients undergoing VATS.
TRIAL REGISTRATION
The trial was registered on Jun 19, 2023 in the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=199315 ), registration number ChiCTR2300072623 (19/06/2023).
Topics: Humans; Acetaminophen; Thoracic Surgery, Video-Assisted; Sufentanil; Oxycodone; Prospective Studies; Nerve Block; Pain, Postoperative; Analgesics; Analgesia, Patient-Controlled; Cough; Mannitol
PubMed: 38172686
DOI: 10.1186/s12871-023-02386-5