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Scientific Reports Aug 2023Anesthesia for laparoscopic sleeve gastrectomy and perioperative management remains a challenge. Several clinical studies indicate that opioid-free anesthesia (OFA) may... (Randomized Controlled Trial)
Randomized Controlled Trial
Anesthesia for laparoscopic sleeve gastrectomy and perioperative management remains a challenge. Several clinical studies indicate that opioid-free anesthesia (OFA) may be beneficial, but there is no consensus on the most optimal anesthesia technique in clinical practice. The aim of our study was to assess the potential benefits and risks of intraoperative OFA compared to multimodal analgesia (MMA) with remifentanil infusion. In a prospective, randomized study, we analyzed 59 patients' data. Primary outcome measures were oxycodone consumption and reported pain scores (numerical rating scale, NRS) at 1, 6, 12, and 24th hours after surgery. Postoperative sedation on the Ramsay scale, nausea and vomiting on the PONV impact scale, desaturation episodes, pruritus, hemodynamic parameters, and hospital stay duration were also documented and compared. There were no significant differences in NRS scores or total 24-h oxycodone requirements. In the first postoperative hour, OFA group patients needed an average of 4.6 mg of oxycodone while the MMA group 7.72 mg (p = 0.008, p < 0.05 statistically significant). The PONV impact scale was significantly lower in the OFA group only in the first hour after the operation (p = 0.006). Patients in the OFA group required higher doses of ephedrine 23.67 versus 15.69 mg (p = 0.039) and more intravenous fluids 1160 versus 925.86 ml (p = 0.007). The mode of anesthesia did not affect the pain scores or the total dose of oxycodone in the first 24 postoperative hours. Only in the first postoperative hour were an opioid-sparing effect and reduction of PONV incidence seen in the OFA group when compared with remifentanil-based anesthesia. However, patients in the OFA group showed significantly greater hemodynamic lability necessitating higher vasopressor doses and more fluid volume.
Topics: Humans; Analgesics, Opioid; Remifentanil; Oxycodone; Prospective Studies; Postoperative Nausea and Vomiting; Pain, Postoperative; Anesthesia; Laparoscopy; Gastrectomy
PubMed: 37542100
DOI: 10.1038/s41598-023-39856-2 -
World Journal of Urology Nov 2023The opioid epidemic in the United States is an ongoing public health crisis that is in part fueled by excessive prescribing by physicians. Percutaneous nephrolithotomy...
INTRODUCTION
The opioid epidemic in the United States is an ongoing public health crisis that is in part fueled by excessive prescribing by physicians. Percutaneous nephrolithotomy (PCNL) is a procedure that conventionally involves opioid prescriptions for adequate post-operative pain control. We aimed to evaluate the feasibility of a non-opioid pain regimen by evaluating post-operative outcomes in PCNL patients discharged without opioids.
MATERIALS AND METHODS
As a quality improvement measure to reduce opioid consumption our department began routinely prescribing oral ketorolac instead of oxycodone-acetaminophen for pain control after PCNL. We retrospectively compared patients undergoing PCNL who had received ketorolac prescriptions (NSAID) to those who received oxycodone-acetaminophen prescriptions (NARC). Demographic, operative, and post-operative factors were obtained and compared in both groups. Peri-operative factors and demographics were compared using either Chi-squared tests, Mann-Whitney U tests. Surgical outcomes were compared between the two groups using Chi-squared tests and Fisher's exact tests. Multivariate logistic regression analysis was performed to determine whether ketorolac use was an independent predictor of post-surgical pain-related encounters. Primary outcome was unplanned pain-related healthcare encounters inclusive of office phone calls, unscheduled office visits, and emergency department (ED) visits. Secondary outcome measures were non-pain-related healthcare encounters, hospital readmissions, pain-related rescue medications prescribed, and post-op complications.
RESULTS
There were similar demographics and peri-operative characteristics amongst patients in both cohorts. There was no significant difference identified between NSAID and NARC regarding unplanned pain-related encounters (8/70, 11.4% vs. 10/70, 14.3%, p = 0.614). However, NARC experienced more unplanned phone calls (42, 60% vs. 24, 34.3%, p = 0.004). Multivariate analysis revealed only prior stone surgery was predictive of pain-related encounters after PCNL (p = 0.035).
CONCLUSION
Our results show that there were no significant differences in pain-related encounters between those who received ketorolac and oxycodone-acetaminophen following PCNL. A non-opioid pathway may mitigate the potential risk associated with opioid prescription without compromising analgesia. Prospective comparative studies are warranted to confirm feasibility.
Topics: Humans; Analgesics, Opioid; Ketorolac; Nephrolithotomy, Percutaneous; Retrospective Studies; Prospective Studies; Anti-Inflammatory Agents, Non-Steroidal; Pain, Postoperative
PubMed: 37733089
DOI: 10.1007/s00345-023-04600-y -
JACS Au Mar 2024Opioids collectively cause over 80,000 deaths in the United States annually. The ability to rapidly identify these compounds in seized drug samples on-site will be...
Opioids collectively cause over 80,000 deaths in the United States annually. The ability to rapidly identify these compounds in seized drug samples on-site will be essential for curtailing trafficking and distribution. Chemical reagent-based tests are fast and simple but also notorious for giving false results due to poor specificity, whereas portable Raman spectrometers have excellent selectivity but often face interference challenges with impure drug samples. In this work, we develop on-site sensors for morphine and structurally related opioid compounds based on in vitro-selected oligonucleotide affinity reagents known as aptamers. We employ a parallel-and-serial selection strategy to isolate aptamers that recognize heroin, morphine, codeine, hydrocodone, and hydromorphone, along with a toggle-selection approach to isolate aptamers that bind oxycodone and oxymorphone. We then utilize a new high-throughput sequencing-based approach to examine aptamer growth patterns over the course of selection and a high-throughput exonuclease-based screening assay to identify optimal aptamer candidates. Finally, we use two high-performance aptamers with of ∼1 μM to develop colorimetric dye-displacement assays that can specifically detect opioids like heroin and oxycodone at concentrations as low as 0.5 μM with a linear range of 0-16 μM. Importantly, our assays can detect opioids in complex chemical matrices, including pharmaceutical tablets and drug mixtures; in contrast, the conventional Marquis test completely fails in this context. These aptamer-based colorimetric assays enable the naked-eye identification of specific opioids within seconds and will play an important role in combatting opioid abuse.
PubMed: 38559723
DOI: 10.1021/jacsau.3c00801 -
Archives of Orthopaedic and Trauma... Nov 2023Oxycodone-acetaminophen is a synergic combination of semisynthetic opioid agonis and analgesic/antipyretic agent, which improves analgesic efficacy. This randomized,... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Oxycodone-acetaminophen is a synergic combination of semisynthetic opioid agonis and analgesic/antipyretic agent, which improves analgesic efficacy. This randomized, controlled study intended to evaluate the analgesic efficacy and tolerance of oxycodone-acetaminophen compared to celecoxib alone in post-total knee arthroplasty (TKA) knee osteoarthritis patients.
METHODS
One hundred and six knee osteoarthritis patients were randomized into oxycodone-acetaminophen group (N = 54) and celecoxib group (N = 52) at a 1:1 ratio. Each patient orally received oxycodone-acetaminophen (5 mg/325 mg, four times per day) or celecoxib (200 mg, twice per day) from 2 h to day (D) 3 after TKA; meanwhile, each patient received 2-day patient-controlled analgesia (PCA). The primary outcome was pain visual analog scale (VAS) score at rest; other assessments were the secondary outcomes.
RESULTS
Pain VAS scores at rest at D1, D2, D3, and pain VAS scores at flexion at D0.5, D1, D2, D3 were lower in oxycodone-acetaminophen group compared to celecoxib group (all P < 0.050). Besides, extra (P < 0.001) and total (P < 0.001) PCA consumption were declined in oxycodone-acetaminophen group compared with celecoxib group. Furthermore, patients' satisfaction score at D3 (P = 0.012) and D7 (P = 0.043) was higher in oxycodone-acetaminophen group versus celecoxib group. Hospital for special surgery knee score (HSS) at preoperation, M1, and M3 did not differ between the two groups (all P > 0.050). The incidences of all adverse events were not varied between oxycodone-acetaminophen and celecoxib groups (all P > 0.050).
CONCLUSION
Oxycodone-acetaminophen exerts superior analgesic efficacy, patients' satisfaction, and similar tolerance compared to celecoxib in post-TKA knee osteoarthritis patients.
Topics: Humans; Celecoxib; Arthroplasty, Replacement, Knee; Osteoarthritis, Knee; Pain, Postoperative; Analgesics; Analgesics, Opioid; Double-Blind Method
PubMed: 37344688
DOI: 10.1007/s00402-023-04943-6 -
Critical Care Medicine Dec 2023The objective of this study was to compare pain control and opioid consumption in critically ill patients who were treated with buprenorphine sublingual or oxycodone...
OBJECTIVES
The objective of this study was to compare pain control and opioid consumption in critically ill patients who were treated with buprenorphine sublingual or oxycodone oral/enteral during ICU admission.
DESIGN
This was a retrospective, parallel, cohort study.
SETTING
General medical or surgical ICUs of a quaternary, urban hospital in Sydney, NSW, Australia.
PATIENTS
Data were obtained for all patients admitted to two general medical or surgical ICU from January 2019 to January 2023. Patients were grouped as those who received buprenorphine sublingual versus oxycodone oral/enteral.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Pain control was compared between a propensity score matched cohort of patients who received buprenorphine versus oxycodone. The primary outcome was the probability of significant pain. A significant pain score was defined as greater than or equal to 4 on the 0-10 Numeric Rating Scale or greater than or equal to 6 on the Behavioral Pain Scale. The study cohort included 1,070 patients (288 buprenorphine and 782 oxycodone). After propensity score matching, there were 288 patients in each group. The mean age of the matched cohort was 64 ± 16 years, 295 (51%) were male, and 359 (62%) had a surgical admission. The median probability of significant pain was 0.16 with buprenorphine and 0.17 with oxycodone (median difference, 0.01; 95% CI, -0.02 to 0.04; p = 0.50). Median opioid consumption in oral morphine milligram equivalents (MMEs) was 65 with buprenorphine and 70 with oxycodone (median difference, -1 mg; 95% CI, -10 to 10 mg; p = 0.73). Median MME per ICU day was 22 with buprenorphine and 22 with oxycodone (median difference, 1 mg; 95% CI, -2 to 5 mg; p = 0.38).
CONCLUSIONS
Buprenorphine sublingual is as effective as oxycodone oral/enteral with regard to pain control and opioid consumption in the ICU. Buprenorphine sublingual is an appropriate option for patients in the ICU who are unable to take oral/enteral medications.
Topics: Humans; Male; Middle Aged; Aged; Aged, 80 and over; Female; Buprenorphine; Analgesics, Opioid; Oxycodone; Retrospective Studies; Cohort Studies; Pain
PubMed: 37642505
DOI: 10.1097/CCM.0000000000006031 -
Drug and Alcohol Dependence Dec 2023Despite the thousands of lives lost during the ongoing opioid crisis, a scarcity of new and effective clinical treatments for opioid use disorder (OUD) remains. To...
Despite the thousands of lives lost during the ongoing opioid crisis, a scarcity of new and effective clinical treatments for opioid use disorder (OUD) remains. To address this unmet need, some researchers have turned to dissociative and psychedelic drugs to treat multiple psychiatric conditions. In particular, low doses of ketamine have been shown to attenuate opioid withdrawal and drug use in clinical and preclinical studies. However, ketamine has misuse liability and dissociative side effects that may limit its widespread application as a treatment for OUD. More recently, (2R,6R)-hydroxynorketamine (HNK), a ketamine metabolite that lacks misuse potential, has gained attention for its effectiveness in depression and stress models. To uncover its role in OUD, we tested the time-dependent effects of (2R,6R)-HNK on oxycodone withdrawal and reinstatement of oxycodone conditioned place preference (CPP). In male and female oxycodone-dependent mice, we found that 24h pretreatment with (2R,6R)-HNK (10 or 30mg/kg, s.c.) reduced the frequency of withdrawal-like behaviors and global withdrawal scores during naloxone-precipitated withdrawal, whereas 1h pretreatment with (2R,6R)-HNK only reduced paw tremors and the sum of global withdrawal scores but not GWS Z-scores. In other experiments, both 1h and 24h pretreatment with (2R,6R)-HNK (30mg/kg, s.c.) blocked drug-induced reinstatement of oxycodone CPP. Finally, we found (2R,6R)-HNK (30mg/kg, sc) had no effect on locomotor activity and thigmotaxis. Together, these results indicate that acute (2R,6R)-HNK has efficacy in some preclinical models of OUD without producing locomotor or anxiety-like side effects.
Topics: Humans; Mice; Male; Female; Animals; Ketamine; Antidepressive Agents; Oxycodone; Hallucinogens
PubMed: 37864957
DOI: 10.1016/j.drugalcdep.2023.110987 -
British Journal of Pain Oct 2023The prescription of opioids in emergency care has been associated with harm, including overdose and dependence. The aim of this trial was to assess restriction of access...
BACKGROUND
The prescription of opioids in emergency care has been associated with harm, including overdose and dependence. The aim of this trial was to assess restriction of access to oxycodone (ROXY), in combination with education and guideline modifications, versus education and guideline modifications alone (standard care) to reduce oxycodone administration in the Emergency Department (ED).
METHODS
An unblinded, active control, randomised controlled trial was conducted in an adult tertiary ED. Participants were patients aged 18-75 years who had analgesics administered in the ED. The primary intervention was ROXY, through removal of all oxycodone immediate release tablets from the ED imprest, with availability of a small supply after senior clinician approval. The intervention did not restrict prescription of discharge medications. The primary outcome measure was oxycodone administration rates. Secondary outcomes were administration rates of other analgesic medications, time to initial analgesics and oxycodone prescription on discharge.
RESULTS
There were 2258 patients eligible for analysis. Oxycodone was administered to 80 (6.1%) patients in the ROXY group and 221 (23.3%) patients in the standard care group (relative risk (RR) 0.26; 95% CI: 0.21 to 0.33; < .001). Tapentadol was prescribed more frequently in the ROXY group (RR 2.17; 95% CI: 1.71-2.74), while there were no differences in prescription of other analgesic medications. On discharge, significantly fewer patients were prescribed oxycodone (RR 0.51; 95% CI: 0.39-0.66) and no differences were observed in prescription rates of other analgesic medications. There was no difference in time to first analgesic (HR 0.94; 95% CI: 0.86-1.02).
CONCLUSIONS
Restricted access to oxycodone was superior to education and guideline modifications alone for reducing oxycodone use in the ED and reducing discharge prescriptions of oxycodone from the ED. The addition of simple restrictive interventions is recommended to enable rapid changes to clinician behaviour to reduce the potential harm associated with the prescribing of oxycodone in the ED.
PubMed: 38107754
DOI: 10.1177/20494637231189031 -
BMJ Supportive & Palliative Care Jan 2024Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using... (Review)
Review
INTRODUCTION
Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using opioids other than morphine.
METHODS
The author conducted a non-systematic literature review in the PubMed/Medline and Embase until 4 October 2022. Eligible studies have evaluated the efficacy of opioids other than morphine for cancer-related breathlessness. Studies focused on sedation, anaesthesia, paediatric patients, opioid toxicity or basic research were excluded. Reviews/meta-analyses and non-English language publications were also excluded.
RESULTS
A total of 1556 records were identified, of which 23 studies including 469 patients who were treated with fentanyl (n=223), oxycodone (n=171) and hydromorphone (n=75) were considered eligible. Six phase II randomised clinical trials (RCTs), four observational studies and four case reports of fentanyl were found. For breathlessness on exertion, fentanyl yielded promising results, but no RCT showed significant superiority of fentanyl to placebo or morphine. For terminal breathlessness, three RCTs, five non-randomised or observational studies and one case report on oxycodone or hydromorphone were found. Although the results of the observational studies suggested that oxycodone and hydromorphone might be effective alternatives to morphine, the superiority over placebo or non-inferiority to morphine had not been demonstrated in the RCTs.
CONCLUSION
As an alternative to morphine, the author recommends fentanyl for breathless crisis or breathlessness on exertion, and oxycodone or hydromorphone for terminal breathlessness in advanced cancer. Larger and well-designed studies based on firm research policies are needed to confirm this current knowledge.
Topics: Child; Humans; Analgesics, Opioid; Dyspnea; Fentanyl; Hydromorphone; Morphine; Neoplasms; Oxycodone
PubMed: 37468224
DOI: 10.1136/spcare-2022-004115 -
Supportive Care in Cancer : Official... Oct 2023Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks...
PURPOSE
Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan.
METHODS
This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE (constipation, nausea and vomiting, delirium, and drowsiness) with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site.
RESULTS
In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (n = 25, 6.3%) was the most frequent, followed by drowsiness (n = 21, 5.3%), nausea and vomiting (n = 19, 4.8%), and constipation (n = 28, 4.6%). The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE.
CONCLUSION
There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.
Topics: Humans; Analgesics, Opioid; Oxycodone; Hydromorphone; Cancer Pain; Tramadol; Prospective Studies; Japan; Prevalence; Longitudinal Studies; Fentanyl; Constipation; Nausea; Vomiting; Delirium
PubMed: 37843639
DOI: 10.1007/s00520-023-08099-2 -
Nature Communications Dec 2023The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new...
The opioid crisis in the United States is primarily driven by the highly potent synthetic opioid fentanyl leading to >70,000 overdose deaths annually; thus, new therapies for fentanyl overdose are urgently needed. Here, we present the first clinic-ready, fully human monoclonal antibody CSX-1004 with picomolar affinity for fentanyl and related analogs. In mice CSX-1004 reverses fentanyl antinociception and the intractable respiratory depression caused by the ultrapotent opioid carfentanil. Moreover, toxicokinetic evaluation in a repeat-dose rat study and human tissue cross-reactivity study reveals a favorable pharmacokinetic profile of CSX-1004 with no safety-related issues. Using a highly translational non-human primate (NHP) model of respiratory depression, we demonstrate CSX-1004-mediated protection from repeated fentanyl challenges for 3-4 weeks. Furthermore, treatment with CSX-1004 produces up to a 15-fold potency reduction of fentanyl in NHP respiration, antinociception and operant responding assays without affecting non-fentanyl opioids like oxycodone. Taken together, our data establish the feasibility of CSX-1004 as a promising candidate medication for preventing and reversing fentanyl-induced overdose.
Topics: Humans; Rats; Mice; Animals; United States; Analgesics, Opioid; Antibodies, Monoclonal; Fentanyl; Drug Overdose; Respiratory Insufficiency
PubMed: 38052779
DOI: 10.1038/s41467-023-43126-0