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PloS One 2024In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences...
BACKGROUND
In 2017, a university-based academic healthcare system changed the opioid default pill count from 30 to 12 pills. Modifying the electronic default pill count influences short-term clinician prescribing practices. We sought to understand the long-term impact on postoperative opioid prescribing habits after an opioid default pill count reduction.
MATERIALS AND METHODS
A retrospective electronic medical record system (EMRS) review was conducted in a healthcare system comprised of seven affiliated hospitals. Patients who underwent a surgical procedure and were prescribed an opioid on discharge between 2017-2021 were evaluated. All prescriptions were converted into morphine equivalents (MME). Analyses were performed with the chi-square test and Bonferonni adjusted t-test.
RESULTS
191,379 surgical procedures were studied. The average quantity of opioids prescribed decreased from 32 oxycodone 5 mg tablets in 2017 to 21 oxycodone 5 mg tablets in 2021 (236 MME to 154 MME, p<0.001). The percentage of patients obtaining a refill within 90 days of surgery varied between 18.3% and 19.9% (p<0.001). Patients with a pre-existing opioid prescription and opioid-naïve patients both had significant reductions in prescription quantities above the default MME (79.7% to 60.6% vs. 65.3% to 36.9%, p<0.001). There was no significant change in refills for both groups (pre-existing 36.7% to 38.3% (p = 0.1) vs naïve 15.0% to 15.3% (p = 0.29)).
CONCLUSIONS
The benefits of decreasing the default opioid pill count continue to accumulate long after the original change. Physician uptake of small changes to default EMRS practices represents a sustainable and effective intervention to reduce the quantities of postoperative opioids prescribed without deleterious effects on outpatient opiate requirements.
Topics: Humans; Male; Female; Analgesics, Opioid; Middle Aged; Retrospective Studies; Pain, Postoperative; Drug Prescriptions; Practice Patterns, Physicians'; Adult; Aged; Electronic Health Records; Oxycodone
PubMed: 38833500
DOI: 10.1371/journal.pone.0304100 -
South African Family Practice :... May 2024Pharmacy professionals working in community pharmacies frequently provide pharmacist-initiated therapy, including codeine-containing medicines. Codeine is an opioid...
BACKGROUND
Pharmacy professionals working in community pharmacies frequently provide pharmacist-initiated therapy, including codeine-containing medicines. Codeine is an opioid with great potential for misuse, adding to the global opioid epidemic burden. Professional pharmacy personnel are the first intervention point in relation to management of codeine use. This study highlights the importance of pharmacy professionals' perceptions and behaviours in combatting the opioid epidemic.
METHODS
A descriptive cross-sectional study was conducted. Simple random sampling included pharmacy professionals in the metropolitan city of Johannesburg. An electronic questionnaire was distributed via e-mail and data analysed descriptively.
RESULTS
Findings indicate that pharmacy personnel routinely ask patients about codeine use (n = 48; 53.9%), avoid dispensing over-the-counter (OTC) codeine as an initial treatment (n = 61; 69%) and express confidence to identify and manage codeine misuse (n = 69; 77.5%). Despite this, increased patient demands for OTC codeine (n = 69; 77.5%) were concerning, highlighting the ease of availability from internet sources (n = 76; 85.4%) and multiple pharmacies (n = 84; 94.4%). Apprehension about the lack of patient awareness on adverse health consequences (n = 66; 74.2%) and the risk of codeine dependence (n = 79; 88.8%) was expressed.
CONCLUSION
Growing concern regarding availability and accessibility of codeine-containing medicines within the community pharmacy sector is highlighted. Adverse health consequences of codeine misuse and dependence are not understood by customers and the ineffective information provided by pharmacy personnel was highlighted as a concern.Contribution: The results of this study give insight to the influence of dispensing personnel's attitude towards the growing challenges with respect to codeine containing medication abuse.
Topics: Humans; Codeine; Cross-Sectional Studies; Female; Male; Adult; Surveys and Questionnaires; Analgesics, Opioid; Pharmacists; Nonprescription Drugs; South Africa; Attitude of Health Personnel; Middle Aged; Opioid-Related Disorders; Community Pharmacy Services; Health Knowledge, Attitudes, Practice
PubMed: 38832385
DOI: 10.4102/safp.v66i1.5862 -
Molecular Pain 2024Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked...
Hyperalgesic priming is a preclinical model of the transition from acute to chronic pain characterized by a leftward shift in the dose-response curve for and marked prolongation of prostaglandin E (PGE)-induced mechanical hyperalgesia, in vivo. In vitro, priming in nociceptors is characterized by a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. In the present in vitro study we tested the hypothesis that a mu-opioid receptor (MOR) agonist opioid analgesic, morphine, can produce priming by its direct action on nociceptors. We report that treatment of nociceptors with morphine, in vitro, produces a leftward shift in the concentration dependence for PGE-induced nociceptor sensitization. Our findings support the suggestion that opioids act directly on nociceptors to induce priming.
Topics: Morphine; Animals; Nociceptors; Dinoprostone; Receptors, Opioid, mu; Analgesics, Opioid; Male; Rats; Ganglia, Spinal; Hyperalgesia; Rats, Sprague-Dawley; Dose-Response Relationship, Drug
PubMed: 38828868
DOI: 10.1177/17448069241260348 -
European Heart Journal. Case Reports Jun 2024Coronary artery bypass graft (CABG) surgery represents a major cardiovascular operation and may be associated with post-operative ST-elevation myocardial infarction...
BACKGROUND
Coronary artery bypass graft (CABG) surgery represents a major cardiovascular operation and may be associated with post-operative ST-elevation myocardial infarction (STEMI) due to graft failure. This is challenging to diagnose and treat as the implanted grafts may be prone to complications when treated percutaneously with drug-eluting stents.
CASE SUMMARY
A man in his 60 s underwent CABG and developed new persistent ST elevations of 2 mm in anterior leads with no significant chest pain, although, administered with intravenous opiates post-operatively. Transthoracic echocardiography was non-diagnostic. Invasive angiography performed emergently showed a thrombotic occlusion of the mid-left anterior descending artery at the site of the anastomosis with the left internal mammary artery (LIMA) graft. Intervention via the graft was considered high risk of complications, therefore, native coronary arteries were used to approach the occlusion, which was successfully cleared with a combination balloon angioplasty with a semi-compliant and then a drug-eluting balloon. The LIMA started working again with the resolution of ST elevation and no immediate complications.
DISCUSSION
Early post-operative ST elevations in continuous leads should not be ignored as they often may be the only feature of new-onset STEMI. Drug-eluting balloons represent a feasible and possibly safer option than drug-eluting stents to treat these conditions.
PubMed: 38828207
DOI: 10.1093/ehjcr/ytae245 -
International Journal of Nanomedicine 2024Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side...
BACKGROUND
Opioids are irreplaceable analgesics owing to the lack of alternative analgesics that offer opioid-like pain relief. However, opioids have many undesirable central side effects. Restricting opioids to peripheral opioid receptors could reduce those effects while maintaining analgesia.
METHODS
To achieve this goal, we developed Tet1-LNP (morphine), a neural-targeting lipid nanoparticle encapsulating morphine that could specifically activate the peripheral opioid receptor in the dorsal root ganglion (DRG) and significantly reduce the side effects caused by the activation of opioid receptors in the brain. Tet1-LNP (morphine) were successfully prepared using the thin-film hydration method. In vitro, Tet1-LNP (morphine) uptake was assessed in differentiated neuron-like PC-12 cells and dorsal root ganglion (DRG) primary cells. The uptake of Tet1-LNP (morphine) in the DRGs and the brain was assessed in vivo. Von Frey filament and Hargreaves tests were used to assess the antinociception of Tet1-LNP (morphine) in the chronic constriction injury (CCI) neuropathic pain model. Morphine concentration in blood and brain were evaluated using ELISA.
RESULTS
Tet1-LNP (morphine) had an average size of 131 nm. Tet1-LNP (morphine) showed high cellular uptake and targeted DRG in vitro. CCI mice treated with Tet1-LNP (morphine) experienced prolonged analgesia for nearly 32 h compared with 3 h with free morphine ( < 0.0001). Notably, the brain morphine concentration in the Tet1-LNP (morphine) group was eight-fold lower than that in the morphine group ( < 0.0001).
CONCLUSION
Our study presents a targeted lipid nanoparticle system for peripheral neural delivery of morphine. We anticipate Tet1-LNP (morphine) will offer a safe formulation for chronic neuropathic pain treatment, and promise further development for clinical applications.
Topics: Animals; Morphine; Ganglia, Spinal; Nanoparticles; Rats; PC12 Cells; Analgesics, Opioid; Male; Neuralgia; Mice; Lipids; Proto-Oncogene Proteins; Peripheral Nerves; Mixed Function Oxygenases; DNA-Binding Proteins; Liposomes
PubMed: 38828199
DOI: 10.2147/IJN.S453608 -
Drug Design, Development and Therapy 2024Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia... (Randomized Controlled Trial)
Randomized Controlled Trial Clinical Trial
PURPOSE
Oxycodone is a potent μ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery.
METHODS
In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1.
RESULTS
All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; =0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; =0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups.
CONCLUSION
For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner.
TRIAL REGISTRATION
Chinese Clinical Trial Registry (ChiCTR2100052085).
Topics: Humans; Oxycodone; Double-Blind Method; Middle Aged; Male; Female; Laparoscopy; Pain, Postoperative; Visceral Pain; Aged; Analgesics, Opioid; Adult; Digestive System Surgical Procedures; Dexmedetomidine; Sufentanil; Analgesia, Patient-Controlled; Flurbiprofen
PubMed: 38828025
DOI: 10.2147/DDDT.S464518 -
Drug Design, Development and Therapy 2024Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an...
PURPOSE
Mechanistic studies showed that morphine may impair the antiplatelet effect of P2Y12 inhibitors. However, Several clinical studies with cardiovascular events as an outcome are contradictory, and the broader impact of this drug interaction on additional organ systems remains uncertain. With multisource data, this study sought to determine the effects of morphine interaction with P2Y12 inhibitors on major adverse outcomes comprehensively, and identify the warning indicators.
PATIENTS AND METHODS
Interaction signals were sought in 187,919 safety reports from the FDA Adverse Event Reporting System (FAERS) database, utilizing reporting odds ratios (repOR). In a cohort of 5240 acute coronary syndrome patients, the analyses were validated, and the biological effects of warning indicators were further studied with Mendelian randomization and mediation analysis.
RESULTS
Potential risk of renal system adverse events in patients cotreated with morphine is significantly higher in FAERS (repOR 4.83, 95% CI 4.42-5.28, false discovery rate adjusted- =3.55*10). The analysis of in-house patient cohorts validated these results with an increased risk of acute kidney injury (adjusted OR: 1.65; 95% CI: 1.20 to 2.26), and we also found a risk of myocardial infarction in patients treated with morphine (adjusted OR: 1.55; 95% CI: 1.14 to 2.11). The Morphine group exhibited diminished Plateletcrit (PCT) levels post-surgery and lower PCT levels were associated with an increased risk of AKI.
CONCLUSION
The administration of morphine in patients treated with P2Y12 receptor inhibitors should be carefully evaluated. PCT may serve as a potential warning indicator for morphine-related renal injury.
Topics: Humans; Morphine; Purinergic P2Y Receptor Antagonists; Acute Coronary Syndrome; Male; Female; Middle Aged; Aged; Platelet Aggregation Inhibitors; Analgesics, Opioid
PubMed: 38828024
DOI: 10.2147/DDDT.S458299 -
Drug Design, Development and Therapy 2024This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of Preadministration of Nalmefene on Sufentanil-Induced Cough During Induction of General Anesthesia in Patients Undergoing Breast Surgery: A Double-Blind Randomized Controlled Trial.
PURPOSE
This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery.
PATIENTS AND METHODS
A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 μg·kg (Group LN), and high-dose nalmefene 0.25 μg·kg (Group HN). Sufentanil 0.5 μg·kg was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery.
RESULTS
Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; < 0.001), but no significant difference was observed between the two groups (=0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181-0.735, =0.008) in Group LN and by 75.9% (95% CI=0.432-0.898, =0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C ( < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups.
CONCLUSION
Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity.
Topics: Humans; Sufentanil; Anesthesia, General; Cough; Female; Naltrexone; Double-Blind Method; Middle Aged; Adult; Breast; Analgesics, Opioid; Dose-Response Relationship, Drug
PubMed: 38828019
DOI: 10.2147/DDDT.S462710 -
Cureus May 2024Perioperative neurocognitive disorders (PNDs) affect a large percentage of people who undergo surgeries that need general anesthesia. There is an increased risk of... (Review)
Review
Perioperative neurocognitive disorders (PNDs) affect a large percentage of people who undergo surgeries that need general anesthesia. There is an increased risk of death and a major disruption to postoperative self-care as a result of this. This study compiles all the relevant materials that the authors have found to investigate postnatal depression and its causes, as well as the methods used to determine the probability and severity of PNDs and how to reduce their risk before surgery. Postnatal depression can have many causes, and this text explores some of them. These include a history of alcohol or opiate use, immunological dysregulation, advanced age, educational background, infections, neurocognitive impairment, and pre-existing chronic inflammatory disorders. It also delves into various methods used to gauge the likelihood and severity of postpartum depression. The following assessment tools were covered: the Clock Drawing Test, Domain-Specific Tests, the Mini-Mental State Examination, and the Montreal Cognitive Assessment. In addition to biochemical markers, neuroimaging techniques play an important role in diagnosis. The Frailty Fried assessment, which measures inertia, sluggishness, lack of physical activity, fatigue, and unintentional weight loss, is a key prognostic sign that is highlighted. There is strong evidence that the index, which is derived from these five characteristics, may accurately predict the likelihood of PNDs. Risk mitigation strategies are also covered in this research. Preoperative brain plasticity-based therapies, such as physical exercise and intensive cognitive training, can significantly reduce the incidence and severity of postoperative neurocognitive disorders. A peripheral nerve block, monitoring cerebral oxygen saturation, dexmedetomidine, and a reduction in anesthesia depth are all ways to improve anesthetic procedures. Methods that lower blood pressure should be avoided, the body temperature should be kept down during surgery, or the time without liquids should be lengthened; all of these raise the risk of postoperative nausea and vomiting and make it worse. Potential approaches include a Mediterranean diet, physical activity, cognitive stimulation, smoking cessation, alcohol reduction, avoidance of anticholinergic medications, and non-steroidal anti-inflammatory drug stewardship, although there is no definitive evidence for successful postoperative neurocognitive rehabilitation procedures. More standardized diagnostic criteria, evaluation methods, and PND classification are urgently needed, according to this study. Different cases of PNDs are characterized by different combinations of tests, cutoff values, and methods because there is a broad variety of diagnostic tests used to make the diagnosis. Until now, PNDs and pre-existing neurocognitive disorders have been diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). With an aging population comes an increase in the occurrence and prevalence of PNDs, which calls for a specific way to classify and describe the condition.
PubMed: 38826940
DOI: 10.7759/cureus.59436 -
The Journal of Toxicological Sciences 2024Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited....
Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through I inhibition in vivo, but its potential to develop torsade de pointes will be small.
Topics: Animals; Dogs; Halothane; Morphine; Heart Rate; Anesthetics, Inhalation; Male; Toxicokinetics; Dose-Response Relationship, Drug; Analgesics, Opioid; Blood Pressure; Electrocardiography; Female; Infusions, Intravenous; Vasodilation; Electrophysiological Phenomena
PubMed: 38825486
DOI: 10.2131/jts.49.269