Use Of Morphine Research Articles

The Effect of Memantine on the Expression of Dopamine Receptors in the Striatum of Male Rats With Morphine Addiction

Background and Objectives: Studies have indicated that the chronic use of morphine can result in physical and psychological dependence. Morphine dependence is associated with several cellular and molecular alterations in the mesocorticolimbic system, and striatal dopamine signaling is involved in this process. In the present study, we aim to investigate possible alterations in the level of dopamine receptors DRD2 and DRD4 in the striatum of male rats following chronic oral administration of morphine and assess the effect of subcutaneous injection of memantine on morphine-induced effects. Methods: In this experimental study, 16 male Wistar rats were randomly divided into four groups: Control, morphine, memantine, and morphine+memantine. The morphine group received increasing doses of morphine (0.1-0.4 mg/kg) via their drinking water for 21 consecutive days. The memantine groups, after receiving distilled water without morphine for 21 days, received a subcutaneous injection of 5 mg memantine. The morphine memantine group received 5 mg of memantine subcutaneously on day 21 and 30 minutes after the last oral administration of morphine. After collecting striatum tissue, dopamine receptor levels were evaluated by the western blotting method. Results: The chronic use of morphine increased the levels of DRD2 and DRD4 compared to the controls. Memantine administration also increased the level of these receptors compared to the controls. In addition, the expression of DRD2 and DRD4 increased in the morphine+ memantine group compared to the memantine group. Conclusion: Morphine affects the expression of dopamine receptors in the striatum. Treatment with memantine can increases dopamine receptors’ expression.

Short-term effects of laparoscopic sleeve gastrectomy combined with reconstruction of the acute His angle on postoperative gastroesophageal reflux disease

Objective: To compare the short-term efficacy of laparoscopic sleeve gastrectomy (LSG) combined with sharp His angle reconstruction (LSG-His) versus traditional LSG. Methods: In this retrospective cohort study we collected clinical data of patients with obesity who had undergone LSG or LSG-His in the Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, from January to June 2022. After excluding patients with incomplete follow-up data and those with hiatal hernia, 83 obese patients, of which 39 who had undergone LSG (LSG group) and 44 who had undergone LSG-His (LSG-His group), were included in the study. The basic steps in LSG-His are the same as in conventional LSG. After continuous suturing of the gastric staple line, one stitch is placed between the proximal side of the gastric greater curvature staple line and the proximal side of the gastric fundus posterior wall with the left diaphragm, and another stitch between the right side of the gastric fundus and the esophagus, reconstructing the sharp His angle. Clinical data, postoperative complications, and follow-up data on weight loss and gastroesophageal reflux disease (GERD) symptoms 1-, 3-, 6-, and 12-months post-discharge were compared between the two groups. GERD symptoms were assessed using the Gastroesophageal Reflux Disease Questionnaire and Reflux Diagnostic Questionnaire. Results: There were no significant differences between the two groups in baseline characteristics, length of hospital stay, hospitalization costs, intraoperative bleeding, postoperative nausea and vomiting, dysphagia, or postoperative complications (all P>0.05). Compared with the LSG group, the LSG-His group had significantly longer operative times (92 [80, 100] minutes vs. 80 [70, 100] minutes, U=2.227, P=0.026), higher postoperative 24-hour pain scores (5.2±1.8 vs. 4.3±1.9, t=-2.065, P=0.041), and higher rates of morphine use (70.5% [31/44] vs. 46.2% [18/39], χ²=4.519, P=0.025). The incidence of new-onset GERD 12 months postoperatively was significantly lower in the LSG-His than the LSG group (10.7% [3/28] vs. 61.3% [19/31], χ²=14.00, P<0.001). According to changes in Gastroesophageal Reflux Disease Questionnaire and Reflux Diagnostic Questionnaire scores, the LSG-His group also had significantly lower rates of exacerbation of GERD (2/16 vs. 5/8, χ²=4.27, P=0.021) and higher rates of GERD remission (12/16 vs. 2/8, χ²=3.62, P=0.032) than did the LSG group. Additionally, excess weight loss rates were significantly higher in the LSG-His group at 3 months [(54.7± 18.7)% vs. (46.5±15.0)% , t=-2.166, P=0.033], 6 months [(73.8±24.7)% vs. (64.0±19.1)% , t=-2.018, P=0.047], and 12 months [(82.9±26.7)% vs. (72.2±19.3)%, t=-2.063, P=0.042] than in the LSG group. Conclusion: Compared with LSG, LSG-His is safe and feasible and achieves better short-term control of postoperative GERD and more effective weight loss. Further large-scale, long-term, prospective studies are needed to confirm the long-term efficacy of LSG-His.

Safety and efficacy of oxycodone for refractory dyspnea in end-stage heart failure patients with chronic kidney disease: a case series of eight patients

BackgroundMorphine is effective in palliative care for patients with end-stage heart failure; however, its use is avoided in patients with impaired renal function because it tends to induce adverse effects. Although oxycodone has been reported to be a useful alternative, the evidence is insufficient. Therefore, we investigated the safety and efficacy of oxycodone in eight patients with end-stage heart failure complicated by chronic kidney disease. MethodsThis single-center retrospective study reviewed patients with end-stage heart failure who were referred to the heart failure multidisciplinary team at our institution and administered oxycodone for refractory dyspnea during hospitalization between January 2011 and December 2018. We examined the details of oxycodone usage, vital signs, and the Modified Borg Scale (MBS), which quantifies the symptoms of dyspnea and adverse events.ResultsOxycodone was administered for refractory dyspnea in eight patients with end-stage heart failure [mean age: 81 years, men: 4, New York Heart Association functional class IV: 8, median left ventricular ejection fraction: < 40% (n = 6) and ≥ 50% (n = 2)]. Renal function was reduced in all patients; the estimated glomerular filtration rate (eGFR) in seven patients was < 30 mL/min/1.73 m2. The median initial intravenous dose of oxycodone was 7.05 mg/day (range: 5–10 mg/day), and the average duration of administration was 15.8 days. Significant decreases in MBS (before: median 9, range 7–10 vs. after: median 2.5, range 1–8; p < 0.01) were observed at a median of 2.0 days (range: 2 h to 7 days) after beginning oxycodone administration. Systolic blood pressure, heart rate, and respiratory rate were not significantly altered after treatment. Adverse events, including constipation, nausea, and tremors, were observed in three patients. However, no lethal adverse events related to oxycodone treatment occurred during treatment.ConclusionsThis study revealed the clinical practice of oxycodone treatment and suggested that it is an alternative therapy as a viable palliative for refractory dyspnea in patients with end-stage heart failure who should avoid the use of morphine.

Central control of opioid-induced mechanical hypersensitivity and tolerance in mice.

Repetitive use of morphine (MF) and other opioids can trigger two major pain-related side effects: opioid-induced hypersensitivity (OIH) and analgesic tolerance, which can be subclassified as mechanical and thermal. The central mechanisms underlying mechanical OIH/tolerance remain unresolved. Here, we report that a brain-to-spinal opioid pathway, starting from μ-opioid receptor (MOR)-expressing neuron in the lateralparabrachial nucleus (lPBNMOR+) via dynorphin (Dyn) neuron in the paraventricular hypothalamic nucleus (PVHDyn+) to κ-opioid receptor (KOR)-expressing GABAergic neuron in the spinal dorsal horn (SDHKOR-GABA), controls repeated systemic administration of MF-induced mechanical OIH and tolerance in mice. The above effect is likely mediated by disruption of dorsal horn gate control for MF-resistant mechanical pain via silencing of the Dyn-positive GABAergic neurons in the SDH (lPBNMOR+ → PVHDyn+ → SDHKOR-GABA → SDHDyn-GABA). Repetitive binding of MF to MORs during repeated MF administration disrupted the above circuits. Targeting the above brain-to-spinal opioid pathways rescued repetitive MF-induced mechanical OIH and tolerance.

Targeting exosomal double-stranded RNA-TLR3 signaling pathway attenuates morphine tolerance and hyperalgesia

Long-term morphine use leads to tolerance and hyperalgesia in patients with chronic pain, with neuroinflammation playing a key role, but its underlying mechanisms remain elusive. This study determines that repeated intrathecal morphine injections increase double-stranded RNA (dsRNA) production in spinal neurons, due to downregulated adenosine deaminase RNA specific 1 (ADAR1) expression. Lentivirus-induced ADAR1 elevation decreases the high levels of intracellular dsRNA and attenuates morphine tolerance and hyperalgesia. dsRNA is released into cerebrospinal fluid via exosomes (Exos) after repeated morphine injections and is taken up by microglia for TLR3-TRIF-IL-6 signaling activation. Blocking Exos release with GW4869 or inhibition of TLR3 signaling mitigates neuroinflammation, preventing the development of morphine tolerance and hyperalgesia. Intrathecal injection of TLR3 inhibitor alone shows analgesic effects in neuropathic pain, and co-administration with morphine amplifies the analgesic efficacy of morphine. These findings demonstrate that targeting dsRNA-TLR3 signaling to mitigate neuroinflammation could be a promising treatment for morphine tolerance.

Impact of opioids on hospital stay and mortality in patients undergoing abdominal surgeries

PurposePostoperative pain management is a critical aspect of surgical care, significantly influencing patient recovery and outcomes. This study aims to evaluate the impact of opioid use on hospital stay and mortality rates among patients undergoing abdominal surgeries in Brazil, where healthcare disparities may affect postoperative outcomes.MethodsThis observational cross-sectional study was conducted at the University Hospital Onofre Lopes in Natal, Brazil. We included 385 patients aged 18 years or older who underwent abdominal surgery in 2023. Data were collected from medical records, focusing on analgesic therapy, opioid types, dosages, and patient demographics. Statistical analyses were performed using JAMOVI software.ResultsOpioid consumption was prevalent among the cohort, with 89.6% of patients receiving opioids postoperatively. Tramadol was the most frequently administered opioid, followed by nalbuphine and morphine. Patients treated with morphine had a significantly extended median hospital stay (15.5 days) compared to those receiving tramadol or nalbuphine (2 days). Morphine use was also associated with a higher mortality rate, with these patients being 16 times more likely to die compared to those on weaker opioids. Older age and extended hospital stays were additional risk factors for increased mortality.ConclusionOpioids were used extensively in this cohort as the main analgesic drug for postoperative pain management after abdominal surgeries. Use was associated with prolonged hospital stay and higher probability of death.

Quantification of morphine in exhaled breath condensate using a double network polymeric hybrid hydrogel functionalized with AuNPs

BackgroundMorphine serves as a foundation for creating other opioid derivatives, such as hydro/oxymorphine and heroin, which possess enhanced pain-relieving properties but are also prone to addiction and abuse. In cases of morphine overdose, it not only affects multiple immune functions but can also cause severe health complications. Given these concerns and the widespread use of morphine, it is crucial to develop efficient, uncomplicated, and precise methods for accurately detecting morphine in various biological and pharmaceutical samples.ResultsIn this investigation, a novel gold nanoparticle (AuNPs)-based double network hydrogel (DNH) nanoprobe has been fabricated for sensitive quantification of morphine in exhaled breath condensate samples. For that, gelatin/agarose DNH was fabricated through a one-step heating-cooling method in the presence of AuNPs, providing not only chemical stability but also prevent the AuNPs aggregation during synthesis process. In this method, the absorbance intensity of the nanoprobe gradually decreased with increasing morphine concentration due to the interaction morphine with AuNPs surface plasmon. The aggregation of AuNPs by addition of morphine was verified by UV-Vis spectrophotometry. The sensor displayed high sensitivity with detection limit of 0.006 µg.mL-1 in the linear range from 0.01 to 1.0 µg.mL-1. A reliable performance was attained for the spectrophotometric method for determination of morphine in the real samples.

233. UTILITY OF SINGLE TRANSHIATAL CHEST DRAINAGE AFTER MINIMALLY INVASIVE OESOPHAGECTOMY: A PROPENSITY-SCORE MATCHED STUDY OF FEASIBILITY

Abstract Background The routine placement of intercostal chest drains remains common practice following minimally invasive oesophagectomy (MIO). Chest drains may contribute to increased post-operative pain and morbidity. The aim of this study was to compare the outcomes of transhiatal chest drain with intercostal chest drain. We analysed use of analgesia, length of hospital stay, and postoperative pulmonary morbidity following MIO. Methods This was a retrospective case-control study of patients undergoing elective MIO at a quaternary centre in Western Australia between September 2016 and September 2023. To reduce confounding, propensity score matching was performed. All patients were identified from a prospectively maintained database. In patients undergoing MIO with exclusive transhiatal drainage, a 19 French Blake’s drain was advanced through the hiatus into the right pleural cavity and positioned adjacent to the anastomosis. Results Thirty patients were included in the study, fifteen of whom had exclusively transhiatal drain placement. Mean total daily oral morphine dose equivalent was significantly lower in the transhiatal drain group (58mg+/-35.8) compared with intercostal drain group (100.8mg+/-64.0) on day 1 (p=0.04). There is no statistically significant difference between the total oral morphine use on days 3 (p=0.44) and 6 (p=0.97). No significant difference was observed in reintervention rate (p=1.00), length of stay (p=0.78) or postoperative pulmonary complications (p=1.00). Conclusion The results of this study suggest that transhiatal drain placement following MIO is associated with a reduction in post-operative pain and no increase in pulmonary complications or length of stay. Larger, prospective studies are needed to further evaluate the safety of single transhiatal chest drain placement following MIO.

Barriers and facilitators to early initiation of palliative care as perceived by nurses working on pneumology and nephrology, a descriptive qualitative study.

Initiation of palliative care early in the disease trajectory is beneficial for patients with a life-limiting disease. However, palliative care is still introduced rather late or not at all. Therefore, this study aims to explore barriers and facilitators to early initiation of palliative care as perceived by nurses working on pneumology and nephrology. A descriptive interview-based study was conducted from a critical realist perspective until data sufficiency was reached. Fifteen nurses presented and discussed a patient for whom palliative care was initiated too late. Template analysis was conducted to develop themes and subthemes. Five key themes were extracted: (1) communication, (2) fear, (3) personal beliefs about life and death, (4) ambiguity in terminology and (5) workload and time pressure. Barriers related to poor interdisciplinary communication were therapeutic obstinance, hierarchy, unawareness of the patient's wishes and fear of saying something inappropriate. Other barriers were patients' religious beliefs which often hindered the use of sedatives or morphine and led to discomfort and time restraints. A palliative support team in hospital and advance care planning (ACP) were enablers for early palliative care. This study started from a negative experience, leading to identification of a lot of barriers and only a few facilitators. The limited sample size and the restriction to two wards within one single hospital limit the diversity of perspectives and the generalisability of the findings. More attention is needed for ACP and interdisciplinary communication. Palliative care, including ACP, and interdisciplinary communication should be included in the basic curricula of all healthcare professional courses. Further research is needed to explore barriers and facilitators to early initiation of palliative care in other healthcare settings and patient populations. This is crucial in order to develop and implement sustainable interventions for specific groups of patients.

Influence of endomorphins-1, 2 on glucose uptake by T and B lymphocytes &lt;i&gt;in vivo&lt;/i&gt;

The main method of treating pain syndrome is the use of morphine and its analogues, which have a wide range of side effects. In this regard, many modern studies are aimed at finding safer analgesic compounds. Currently, among morphine analogues, much attention is paid to endogenous opioid peptides, which, along with an analgesic effect, have pronounced immunoregulatory properties. It is now known that the functional activity of immune cells is ensured by metabolism. This process supplies cells with the energy necessary for activation, differentiation, proliferation, apoptosis, etc. Glucose metabolism plays a key role in ensuring the functions of immune cells. The aim of this work is to evaluate the effect of endomorphins-1, 2 on the characteristics of glucose uptake by T and B lymphocytes in vivo. The subjects of the study were white male mice, peptides were administered to mice intraperitoneally at a dose of 100 ìg/kg, and glucose uptake by cells was assessed using fluorescent analogues of glucose (2-NBDG). It was found that endomorphin-1 did not affect at the intensity of glucose consumption in both T and B cells. Administration of endomorphin-2, on the contrary, led to a significant increase in glucose uptake in T lymphocytes. However, the level of glucose consumption in B cells after administration of endomorphin-2 did not change significantly. In a study of two subsets of T lymphocytes, it was noted that endomorphin-2 leads to an increase in glucose uptake in both CD4+ and CD4-T cells. Administration of endomorphin-1 had no significant effect on the level of uptake of this substrate in both subsets of T lymphocytes. Proliferating B lymphocytes increased glucose consumption in the presence of LPS after administration of endomorphin-2. Both endomorphins did not have a significant effect on glucose consumption in proliferating CD4+ and CD4-T cells. Thus, endomorphin-1, unlike endomorphin-2, does not have a significant effect on glucose metabolism in T and B cells. Taking into account the role of glycolysis in the functioning of immune cells and inflammation, it can be concluded that the use of endomorphin-1 may be associated with a lower risk of immune system-related side effects.

Nalbuphine versus morphine: an adjuvant to spinal anesthesia for controlling pain after total knee arthroplasty: a propensity score-matched analysis.

Nalbuphine, a synthetic k-agonist and µ-antagonist, provides efficient pain relief while reducing opioid-related adverse effects. This study aims to compare the efficacy of intrathecal nalbuphine (ITN) with intrathecal morphine (ITM) for post-TKA pain. A retrospective cohort analysis of 131 patients who underwent TKA with spinal anesthesia (SA), a single shot of adductor canal block, and periarticular injections was conducted. The patients were divided into 2 groups, Group N received 0.8mg nalbuphine, and Group M received 0.2mg morphine as an adjuvant to SA. Propensity-score matching was employed to compare the visual analog scales (VAS) of postoperative pain intensity, cumulative morphine use (CMU), maximum knee flexion angle, straight leg raise (SLR) ability, incidence of postoperative nausea and vomiting (PONV), and length of hospital stay (LHS). The mean VAS of group M were significantly lower than group N at 6, 12, 18, and 24h (P < 0.01). Group M had lower CMU than group N at 24h (P < 0.01) and 48h (P < 0.01), while there was no significant difference between groups in terms of knee flexion angle and SLR at any time point. Additionally, 29.3 and 57.9% of patients in group N and M experienced PONV, respectively (p = 0.04), and group N had significantly shorter LHS compared to group M (P < 0.001). Although, intrathecal morphine (ITM) still provides better pain control particularly in the first 24h, patients who received intrathecal nalbuphine (ITN) had significantly fewer incidence of PONV, and shorter LHS.

Comparison of low-dose ketamine to methadone for postoperative pain in opioid addicts: a randomized clinical trial.

Postoperative pain can lead to several complications. The effectiveness of different opioids in relieving pain after surgery has been widely studied. However, managing pain in patients with opioid addiction is still challenging. This study aimed to examine the impact of ketamine and methadone on postoperative pain in patients with addiction. This was a non-inferiority randomized clinical trial. All included patients were monitored for morphine use, pain scores, and vital signs every 3 h. The intervention group received 0.5 mg/kg ketamine administered intravenously every 6 h. The control group received 5 mg of methadone intramuscularly every 8 h. The patient received intravenous morphine if their visual analog scale was above 3. All side effects in each group were recorded. Two hundred and twenty patients were included in this study. There were 127 men (57.7%) with an average age of 57.1 ± 19.5 and 93 women (42.3%) with an average age of 57.1 ± 21.0. There were no significant differences in demographic characteristics between the groups. There was no significant difference in the dose or frequency of morphine administration between groups. There was no significant difference between the groups in pain scores and vital signs at different time points. Drug side effects, including delirium and gastrointestinal symptoms, did not differ significantly between the methadone and ketamine groups. Our clinical data support the hypothesis that ketamine is not inferior to methadone in patients with addiction. Future randomize clinical trials are needed to confirm these observations.

Fracture pain in children in the emergency department: the impact of a new pain management procedure

PurposeTo compare compliance with the French national guidelines before and after the implementation (in 2018) of a new protocol on acute fracture pain management in the pediatric emergency department of a French university medical center.MethodsWe conducted a retrospective, before-after study in patients aged below 16 years presenting at the pediatric emergency department with a fracture. We compared pain management before (in 2017) and after (in 2019 and 2020) implementation of the new procedure. The primary endpoint was appropriate pain management, defined as (i) an appropriate initial assessment of pain, (ii) appropriate treatment with analgesic drugs (acetaminophen for mild pain, acetaminophen and ibuprofen for moderate pain, ibuprofen and morphine for severe pain) and (iii) reassessment of the pain intensity.Results572 patients were included (mean age: 6.5 years; male: 60%). 190 in 2017 and 382 in 2019–2020. Pain management was appropriate for 40% of the patients in 2017 and 52% in 2019–2020 (p = 0.004). Pain was rated for 98% of patients in 2017 vs. 100% in 2019–2020 (p = 0.04). The frequency of appropriate treatment for mild pain and moderate pain increased significantly from 52 to 76% and from 0 to 44%, respectively. The administration of ibuprofen increased by 26% points (from 3 to 20 patients treated) and the administration of morphine increased by 29% points (from 1 to 17 patients treated). Pain reassessment rose significantly from 21 to 43%. Levels of compliance with the guidelines were similar in 2019 and 2020. Analgesia was significantly more effective in 2019–2020 than in 2017 (in 20% vs. 14% of the patients, respectively; p = 0.005).ConclusionAfter the implementation of a new protocol for the management of acute fracture pain, we observed an increase in compliance with the guidelines. Although the use of ibuprofen and morphine rose significantly as did the frequency of pain reassessment, further improvements are required.

Low dose of morphine to relieve dyspnea in acute respiratory failure: the OpiDys double-blind randomized controlled trial

BackgroundMorphine relieves dyspnea in various clinical circumstances. Whether or not this applies to patients admitted to intensive care units (ICUs) for acute respiratory failure (ARF) is unknown. We evaluated the efficacy and safety of low-dose morphine on dyspnea in patients admitted to the ICU for ARF.MethodsIn this single-center, double-blind, phase 2, randomized, controlled trial, we assigned non-intubated adults admitted to the ICU for ARF with severe dyspnea, defined by a visual analog scale for dyspnea (dyspnea-VAS) from zero (no dyspnea) to 100 mm (worst imaginable dyspnea) ≥40 mm, to receive a low dose of Morphine Hydrochloride (intravenous titration followed by subcutaneous relay) or Placebo. All patients received standard therapy, including etiological treatment and non-invasive respiratory support.ResultsTwenty-two patients were randomized, 11 in each group. The average dyspnea (median [interquartile range]) over 24 hours did not significantly differ between the two groups (40 [25 – 43] mm in the Morphine group vs. 40 [36 – 49] mm in the Placebo group, p=0.411). Dyspnea-VAS was lower in the Morphine group than in the Placebo group at the end of intravenous titration (30 [11 – 30] vs. 35 [30 – 44], p=0.044) and four hours later (18 [10 – 29] vs. 50 [30 – 60], p=0.043). The cumulative probability of intubation was higher in the Morphine group than in the Placebo group (p=0.046)ConclusionIn this phase 2 pilot trial, morphine did not improve 24-hour average dyspnea in adult patients with ARF, even though it had a statistically significant immediate effect. Of concern, Morphine use was associated with a higher intubation rate.Trial registrationThe protocol was declared on the ClinicalTrial.gov database (no. NCT04358133) and was published in September 2022.

Implementing the eat, sleep, console method into a tertiary care delivery center

BackgroundInfants experiencing Neonatal Opioid Withdrawal Syndrome (NOWS) after birth has been a significant public health issue since the opioid crisis began in the U.S. Traditional assessment tools for symptom management have historically resulted in prolonged hospitalization and continued exposure to opioids after birth to treat them. PurposeEat, Sleep, Console (ESC) was implemented to replace a popular NOWS assessment tool in a neonatal intensive care unit at a large urban children's hospital's maternity center. The aim was to determine whether using ESC would decrease length of hospitalization, use of morphine for treatment, as well as increase the number of direct discharges from the postpartum unit. ResultsALOS decreased from 9.2 days to 6.2 days, a 33% reduction. Morphine treatment initiation decreased from 21.7% to 3.8%, an 82.4% reduction. Neither group included infants treated with a second line medication. Finally, the discharge rate improved by 47% directly from the postpartum unit. ConclusionsUsing ESC, all identified outcomes regarding management of infants with NOWS improved. Wide-scale use of ESC could have multiple benefits for this patient population including a reduction in healthcare costs and prolonged exposure to opioids after birth, as well as preservation of the mother-infant dyad in the immediate postpartum period. Further research is needed to study the long-term impact of the ESC method.

Wastewater-based epidemiology to monitor 68 NPS/conventional drug use in Taipei metropolitan area in Taiwan during and after COVID-19 pandemic

Amidst far-reaching COVID-19 effects and social constraints, this study leveraged wastewater-based epidemiology to track 38 conventional drugs and 30 new psychoactive substances (NPS) in northern Taiwan. Analyzing daily samples from four Taipei wastewater plants between September 2021 and January 2024—encompassing club reopenings, holidays, Lunar New Year, an outbreak, and regular periods—thirty-one drugs were detected, including 5 NPS. Tramadol, zolpidem tartrate, CMA, and MDPV were newly detected in Taiwanese sewage with frequency of 1.4 %− 89.0 %. Conventional drug use typically increased post-pandemic, aside from benzodiazepines and methadone. Methamphetamine showed 100 % frequency, indicating ongoing daily consumption despite COVID-19 measures. Methamphetamine and morphine's consumption dipped then rose around club reopening, hinting at limited access. The consumption trend of methadone appeared to compensate for the use of morphine. Ketamine and NPS demonstrated similar patterns throughout the entire period. NPS as party drugs seemed influenced by an unstable supply chain and complexities in implementation. Benzodiazepines, commonly abused alongside synthetic cathinones in Taiwan exhibited an opposing trend to NPS while aligned with acetaminophen, suggesting elevated stress and anxiety levels during the pandemic. No significant differences were observed in drug consumption between weekdays and weekends, potentially indicating that COVID-19 measures blurred the traditional distinctions between these timeframes. Environmental ImplicationNew psychoactive substances refer to chemically modified variants of controlled drugs designed to mimic the effects of the original drugs while evading modern detection methods, categorizing them as hazardous materials. The study presents a sewage monitoring project conducted from 2021 to 2024, collecting samples from four WWTPs to analyze NPS and conventional drug trends during and after the COVID-19 pandemic. The findings uncovered connections between drug consumption patterns and pandemic-related policies. In light of the persistent drug abuse and their environmental presence, the results bear critical importance for both environmental and public health. We provide a thorough assessment of these relationships and prioritize areas for future research.

Preoperative Gabapentin for Pain Control: A Randomized, Placebo-controlled Clinical Trial in Patients Undergoing Inguinal Hernioplasty

PurposeThe perioperative use of gabapentin has been suggested to reduce postoperative pain and opioid consumption. However, there is a variation in clinical practice, the type of surgery and the administration time seem to be distinct between the available studies. We assess whether gabapentin administered before surgery reduces postoperative pain in patients who have undergone inguinal hernioplasty. DesignThis is a double-blind, randomized, and placebo-controlled trial. MethodsSeventy-seven patients scheduled for inguinal hernioplasty were randomized in two groups to receive gabapentin (900 mg) or placebo in the perioperative period. The primary outcome was analgesia measured by visual analog scale up to 30 days after surgery. The secondary outcomes such as morphine consumption, nausea, headache, and sedation have been also described. FindingsPatients who received gabapentin had lower postoperative pain scores compared to the control group, P < .001. The postoperative morphine use was significantly lower in the gabapentin (5.3%) versus placebo group (74.4%), P < .001. No significant difference between groups was observed for the occurrence of adverse events. ConclusionsThe perioperative administration of gabapentin was effective in reducing postoperative pain and had an important effect in decreasing morphine use. Together, our data reveal a long-lasting opioid-sparing effect of gabapentin in patients who underwent inguinal hernioplasty.

Effect of Morphine Used to Relieve Dyspnea Due to Heart Failure on Delirium.

Background: Delirium management is crucial in palliative care. Morphine effectively relieves dyspnea due to heart failure. However, the effect of morphine, which is used to relieve dyspnea due to heart failure, on the incidence of delirium has not been examined to date. Objective: To evaluate the effect of morphine, which is used to relieve dyspnea due to heart failure, on delirium. Design: Retrospective observational study. Setting/Subjects: Subjects were identified from Osaka University Hospital records, located in Japan, from January 1, 2010, to September 30, 2021. The case group consisted of admissions for heart failure or cardiomyopathy registered in electronic medical records. Morphine was administered to relieve dyspnea due to heart failure, and no surgeries or procedures were performed. The control group consisted of admissions for heart failure or cardiomyopathy in the Diagnosis Procedure Combination (DPC) database, which did not include administration of morphine, oxycodone, or fentanyl during the hospitalization period and patients did not undergo surgery or any other procedure. Measurements: The incidence of delirium was assessed. Results: The odds ratios for morphine in the multivariate logistic regression analysis with propensity score and univariate logistic regression analysis after propensity score matching were 1.406 (95% confidence interval (CI) [0.249-7.957]) and 1.034 (95% CI [0.902-1.185]), respectively. Conclusions: Morphine, which is used to relieve dyspnea due to heart failure, had minimal effect on the incidence of delirium. This information is likely to be beneficial for the future use of morphine in the management of dyspnea in patients with heart failure.

Systemic lidocaine versus erector spinae plane block for improving quality of recovery after laparoscopic cholecystectomy: A randomized controlled trial

Study objectiveTo compare intravenous lidocaine, ultrasound-guided erector spinae plane block (ESPB), and placebo on the quality of recovery and analgesia after laparoscopic cholecystectomy. DesignA prospective, triple-arm, double-blind, randomized, placebo-controlled non-inferiority trial. SettingA single tertiary academic medical center. Patients126 adults aged 18–65 years undergoing elective laparoscopic cholecystectomy. InterventionsPatients were randomly allocated to one of three groups: intravenous lidocaine infusion (1.5 mg/kg bolus followed by 2 mg/kg/h) plus bilateral ESPB with saline (25 mL per side); bilateral ESPB with 0.25% ropivacaine (25 ml per side) plus placebo infusion; or bilateral ESPB with saline (25 ml per side) plus placebo infusion. MeasurementsThe primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. The non-inferiority of lidocaine versus ESPB was assessed with a margin of −6 points and 97.5% confidence interval (CI). Secondary outcomes included 24-h area under the curve (AUC) for pain scores, morphine consumption, and adverse events. Main results124 patients completed the study. Median (IQR) 24-h QoR-15 scores were 123 (117–127) for lidocaine, 124 (119–126) for ESPB, and 112 (108–117) for placebo. Lidocaine was non-inferior to ESPB (median difference –1, 97.5% CI: −4 to ∞). Both lidocaine (median difference 9, 95% CI: 6–12, P < 0.001) and ESPB (median difference 10, 95% CI: 7–13, P < 0.001) were superior to placebo. AUC for pain scores and morphine use were lower with lidocaine and ESPB versus placebo (P < 0.001 for all), with no significant differences between lidocaine and ESPB. One ESPB patient reported a transient metallic taste; no other block-related complications occurred. ConclusionsFor patients undergoing laparoscopic cholecystectomy, intravenous lidocaine provides a non-inferior quality of recovery compared to ESPB without requiring specialized regional anesthesia procedures. Lidocaine may offer a practical and accessible alternative within multimodal analgesia pathways.

Tsc22d3 promotes morphine tolerance in mice through the GPX4 ferroptosis pathway.

Morphine tolerance refers to gradual reduction in response to drug with continuous or repeated use of morphine, requiring higher doses to achieve same effect. The morphine tolerance dataset GSE7762 profiles, obtained from gene expression omnibus (GEO) database, were used to identify differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) was applied to explore core modules of DEGs related to morphine tolerance. Core genes were input into Comparative Toxicogenomics Database (CTD). Animal experiments were performed to validate role of Tsc22d3 in morphine tolerance and its relationship with ferroptosis-related pathway. 500 DEGs were identified. DEGs were primarily enriched in negative regulation of brain development, neuronal apoptosis processes, and neurosystem development. Core gene was identified as Tsc22d3. Tsc22d3 gene-associated miRNAs were mmu-miR-196b-5p and mmu-miR-196a-5p. Compared to Non-morphine tolerant group, Tsc22d3 expression was significantly upregulated in Morphine tolerant group. Tsc22d3 expression was upregulated in Morphine tolerant+Tsc22d3_OE, expression of HIF-1alpha, GSH, GPX4 in GPX4 ferroptosis-related pathway showed a more pronounced decrease. As Tsc22d3 expression was downregulated in Morphine tolerant+Tsc22d3_KO, expression of HIF-1alpha, GSH, GPX4 in GPX4 ferroptosis-related pathway exhibited a more pronounced increase. Upregulation of Tsc22d3 in Morphine tolerant+Tsc22d3_OE led to a more pronounced increase in expression of apoptosis proteins (P53, Caspase-3, Bax, SMAC, FAS). The expression of inflammatory factors (IL6, TNF-alpha, CXCL1, CXCL2) showed a more pronounced increase with upregulated Tsc22d3 expression in Morphine tolerant+Tsc22d3_OE. Tsc22d3 is highly expressed in brain tissue of morphine-tolerant mice, activating ferroptosis pathway, enhancing apoptosis, promoting inflammatory responses in brain cells.