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Journal of Pain & Palliative Care... Jun 2024Myoclonus is a relatively rare involuntary movement that is often observed in palliative care settings and that can cause patient distress. The purpose of this study is...
Myoclonus is a relatively rare involuntary movement that is often observed in palliative care settings and that can cause patient distress. The purpose of this study is to investigate the occurrence of myoclonus and countermeasures against it in terminally ill patients with cancer diagnosed by palliative care specialists at Komaki City Hospital, Japan. We retrospectively reviewed patients with terminal cancer who received palliative care consultations between January 2018 and May 2019 and who were diagnosed with myoclonus by palliative care specialists, using electronic medical records. Patient demographics, time from onset of myoclonus to death, daily opioid use, countermeasures, and outcome of myoclonus were assessed. Of 360 patients examined during this period, 45 (12.5%) were diagnosed with myoclonus. Median age was 71 (range, 43-88) years; median time from onset of myoclonus to death was 8 days (range, 0-56); opioid usage was present in 39 patients (morphine, oxycodone, and fentanyl: = 6, 21, and 12, respectively); and median oral morphine equivalent at onset of myoclonus was 60 mg (range, 12-336 mg). Myoclonus treatment was administered to 21 patients (opioid dose reduction, opioid switching, and others: = 14, 3, and 4, respectively). Myoclonus is a common complication in patients with terminal cancer.
Topics: Humans; Myoclonus; Retrospective Studies; Aged; Male; Female; Middle Aged; Aged, 80 and over; Neoplasms; Adult; Terminally Ill; Palliative Care; Analgesics, Opioid; Japan
PubMed: 38722682
DOI: 10.1080/15360288.2024.2345326 -
Frontiers in Surgery 2024We aimed to compare the anesthesia induction effects of oxycodone and sufentanil on postoperative pain in patients undergoing laparoscopic gallbladder-preserving...
Comparison of the analgesic effects of oxycodone vs. sufentanil on postoperative pain after laparoscopic gallbladder-preserving cholecystolithotomy: a prospective randomized controlled trial.
BACKGROUND
We aimed to compare the anesthesia induction effects of oxycodone and sufentanil on postoperative pain in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy, as well as changes in serum levels of inflammatory factors (TNF-α, IL-6, and IL-10) in the perioperative period.
METHODS
Sixty patients who underwent laparoscopic gallbladder-preserving cholecystolithotomy were evenly divided into oxycodone (O) and sufentanil (S) groups. In groups O and S, oxycodone (0.3 mg/kg) and sufentanil (0.3 ug/kg) were administered, respectively, followed by propofol (2 mg/kg) and rocuronium (0.6 mg/kg). In both groups, the intraoperative electroencephalography double-frequency index was used to guide the use of sedative and analgesic drugs, assessing the follow-up analgesic effect (VAS), degree of sedation (Ramsey), and postoperative complications at seven different time points (0, 0.5, 2, 4, 6, 8, and 24 h postoperatively).
RESULTS
Compared with the S group, patients in the O group exhibited lower VAS scores within 24 h postoperatively ( < 0.001), but there was no statistical difference between wound and shoulder pain scores (> 0.05). Regarding postoperative awakening and extubation duration, O group patients experienced shorter times and better remedial analgesia ( < 0.05). In terms of the degree of sedation, the Ramsay score decreased at 0 h postoperatively compared with the S group ( < 0.001).
CONCLUSION
Compared with sufentanil, oxycodone anesthesia induced better postoperative analgesia and less inflammatory responses in patients undergoing laparoscopic gallbladder-preserving cholecystolithotomy.
CLINICAL TRIAL REGISTRATION
This study has been approved by the Ethics Committee of Peking University Shougang Hospital, with ethical approval (No. IRBK-2020-009), and has completed registration in the Chinese Clinical Trials Register (http://www.chictr.org.cn/) (ChiCTR2000031230).
PubMed: 38721023
DOI: 10.3389/fsurg.2024.1382759 -
The Journal of Innovations in Cardiac... Apr 2024Providing adequate analgesia perioperatively during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation can be a challenge. The objective of our...
Providing adequate analgesia perioperatively during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation can be a challenge. The objective of our study was to assess the efficacy and safety of the erector spinae plane (ESP) block technique in providing analgesia and minimizing the risk of opioid use in high-risk patient populations. We enrolled consecutive patients >18 years of age undergoing S-ICD implantation from February 2020 to February 2022 at our center prospectively. Patients were randomly assigned to receive the ESP block or traditional wound infiltration. A total of 24 patients were enrolled, including 13 patients randomized to ESP block and 11 patients as controls who received only wound infiltration. The primary outcome assessed was the overall use of perioperative analgesic medications in the ESP block group versus the surgical wound infiltration group. A significant reduction in intraoperative fentanyl use was observed [median ([interquartile range]) in the ESP block group (0 [0-50] μg) compared to the wound infiltration block group (75 [50-100] μg) ( = .001). The overall postoperative day (POD) 0 fentanyl use was also significantly decreased (75 [50-100] μg) in the ESP block group compared to the surgical wound infiltration group (100 [87.5-150] μg) ( = .049). There was also a trend of decreased POD 0 oxycodone-acetaminophen use. Finally, the number of days to discharge was less in the ESP block group. These results indicate that ESP block is an innovative, safe, and effective technique that decreases intraoperative and postoperative opioid consumption and may be a useful adjunct pain-management technique in these high-risk patients. Larger studies are needed to further validate its use.
PubMed: 38715552
DOI: 10.19102/icrm.2024.15043 -
The Cleft Palate-craniofacial Journal :... May 2024To evaluate the safety of same-day discharge for patients undergoing primary cleft palate repair.
OBJECTIVE
To evaluate the safety of same-day discharge for patients undergoing primary cleft palate repair.
DESIGN
Single-surgeon retrospective review.
SETTING
Tertiary care institution.
PATIENTS/PARTICIPANTS
40 consecutive patients that underwent primary cleft palate repair by a single surgeon from September 2018 to June 2023.
INTERVENTIONS
Same-day discharge versus overnight admission after primary palatoplasty.
MAIN OUTCOME MEASURES
30-day readmission, reoperation, wound and all-cause complication rate and 1-year fistula incidence.
RESULTS
Of 40 total cases, 20 patients were discharged on the same calendar day and 20 patients were admitted for overnight stay following primary cleft palate repair. In the same-day discharge group, readmission incidence was 10%(n = 2), wound complication incidence was 5%(n = 1), and postoperative complication incidence was 15%(n = 3). In comparison, patients admitted overnight had a readmission incidence of 5%(n = 1, = 1.00), wound complication incidence of 10%(n = 2, = 1.00), and postoperative complications of 20%(n = 4, = 1.00) No patients had 30-day reoperations or fistulas at 1 year. A higher proportion of admitted patients held a preoperative diagnosis of unilateral cleft palate and alveolus (Veau 3) as compared to patients discharged on the same day ( = .019). During the postoperative hospital course, admitted patients received significantly more oxycodone at median of 2 doses (IQR 1.00-3.75) and acetaminophen at a median of 4 doses (IQR 3.00-5.00) than patients with same-day discharge with a median of 1 dose (IQR 0.00 -1.00, < .001).
CONCLUSIONS
In a low-risk patient population, same-day discharge following primary cleft palate repair may be safely undertaken and result in similar short-term outcomes and 1-year fistula incidence as patients admitted for overnight stay.
PubMed: 38715425
DOI: 10.1177/10556656241251932 -
Knee Surgery, Sports Traumatology,... May 2024The purpose of the study was to identify prognostic risk factors for prolonged opioid use at 2 and 6 weeks after hip arthroscopy using data from the Femoroacetabular...
Risk factors for prolonged opioid consumption following hip arthroscopy: A secondary analysis of the Femoroacetabular Impingement RandomiSed controlled Trial and embedded cohort study.
PURPOSE
The purpose of the study was to identify prognostic risk factors for prolonged opioid use at 2 and 6 weeks after hip arthroscopy using data from the Femoroacetabular Impingement RandomiSed controlled Trial and its external validation cohort study.
METHODS
Opioids were prescribed for postoperative pain management at the surgeon's discretion, with a majority being prescribed a combination of oxycodone and paracetamol (5/325 mg). Prolonged opioid use was defined as the ongoing use of any dosage of opioids reported at either 2 or 6 weeks after surgery to treat femoroacetabular impingement, as recorded in the patient's study medication log. Multivariable logistic regressions were performed to evaluate patient and surgical characteristics, such as preoperative opioid use, type of surgical procedure and intraoperative cartilage state that may be associated with prolonged opioid use at either 2 and 6 weeks postoperatively.
RESULTS
A total of 265 and 231 patients were included for analysis at 2 and 6 weeks postoperatively, respectively. The median age of participants was 35 years (interquartile range [IQR]: 27-42) and 33% were female. At 2 weeks postoperatively, female sex (odds ratio [OR]: 2.56; 95% confidence interval: [CI] 1.34-4.98, p = 0.005), higher body mass index (BMI) (OR: 1.10; 95% CI: 1.02-1.18, p = 0.009), active tobacco use (OR: 4.06; 95% CI: 1.90-8.97, p < 0.001), preoperative opioid use (OR: 10.1; 95% CI: 3.25-39.1, p < 0.001) and an Outerbridge classification of ≥3 (OR: 2.33; 95% CI: 1.25-4.43, p = 0.009) were significantly associated with prolonged opioid use. At 6 weeks postoperatively, only preoperative opioid use was significantly associated with prolonged opioid consumption (OR: 10.6; 95% CI: 3.60-32.6, p < 0.001).
CONCLUSION
Preoperative opioid use was significantly associated with continued opioid use at 2 and 6 weeks postoperatively. Specific patient factors including female sex, higher BMI, active tobacco use and more severe cartilage damage should be considered in developing targeted strategies to limit opioid use after surgery.
LEVEL OF EVIDENCE
Level III.
PubMed: 38713876
DOI: 10.1002/ksa.12204 -
Fluids and Barriers of the CNS May 2024Triptans are anti-migraine drugs with a potential central site of action. However, it is not known to what extent triptans cross the blood-brain barrier (BBB). The aim...
BACKGROUND
Triptans are anti-migraine drugs with a potential central site of action. However, it is not known to what extent triptans cross the blood-brain barrier (BBB). The aim of this study was therefore to determine if triptans pass the brain capillary endothelium and investigate the possible underlying mechanisms with focus on the involvement of the putative proton-coupled organic cation (H/OC) antiporter. Additionally, we evaluated whether triptans interacted with the efflux transporter, P-glycoprotein (P-gp).
METHODS
We investigated the cellular uptake characteristics of the prototypical H/OC antiporter substrates, pyrilamine and oxycodone, and seven different triptans in the human brain microvascular endothelial cell line, hCMEC/D3. Triptan interactions with P-gp were studied using the IPEC-J2 MDR1 cell line. Lastly, in vivo neuropharmacokinetic assessment of the unbound brain-to-plasma disposition of eletriptan was conducted in wild type and mdr1a/1b knockout mice.
RESULTS
We demonstrated that most triptans were able to inhibit uptake of the H/OC antiporter substrate, pyrilamine, with eletriptan emerging as the strongest inhibitor. Eletriptan, almotriptan, and sumatriptan exhibited a pH-dependent uptake into hCMEC/D3 cells. Eletriptan demonstrated saturable uptake kinetics with an apparent K of 89 ± 38 µM and a J of 2.2 ± 0.7 nmol·min·mg protein (n = 3). Bidirectional transport experiments across IPEC-J2 MDR1 monolayers showed that eletriptan is transported by P-gp, thus indicating that eletriptan is both a substrate of the H/OC antiporter and P-gp. This was further confirmed in vivo, where the unbound brain-to-unbound plasma concentration ratio (K) was 0.04 in wild type mice while the ratio rose to 1.32 in mdr1a/1b knockout mice.
CONCLUSIONS
We have demonstrated that the triptan family of compounds possesses affinity for the H/OC antiporter proposing that the putative H/OC antiporter plays a role in the BBB transport of triptans, particularly eletriptan. Our in vivo studies indicate that eletriptan is subjected to simultaneous brain uptake and efflux, possibly facilitated by the putative H/OC antiporter and P-gp, respectively. Our findings offer novel insights into the potential central site of action involved in migraine treatment with triptans and highlight the significance of potential transporter related drug-drug interactions.
Topics: Tryptamines; Animals; Endothelial Cells; Humans; Mice, Knockout; Blood-Brain Barrier; Brain; Cell Line; Mice; Mice, Inbred C57BL; Biological Transport; ATP Binding Cassette Transporter, Subfamily B, Member 1; Male; Antiporters; Pyrilamine; ATP Binding Cassette Transporter, Subfamily B; Pyrrolidines
PubMed: 38711118
DOI: 10.1186/s12987-024-00544-6 -
Psychopharmacology Jul 2024Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is...
RATIONALE
Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain.
OBJECTIVE
Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays.
METHODS
Cell-based assays were used to measure receptor binding and intrinsic efficacy of ITI-333; animal models were employed to assess effects on opioid reinstatement, precipitated oxycodone withdrawal, and drug abuse liability.
RESULTS
In vitro, ITI-333 is a potent 5-HT receptor antagonist (K = 8 nM) and a biased, partial agonist at μ-opioid (MOP) receptors (K = 11 nM; lacking β-arrestin agonism) with lesser antagonist activity at adrenergic α (K = 28 nM) and dopamine D (K = 50 nM) receptors. In vivo, ITI-333 blocks 5-HT receptor-mediated head twitch and MOP receptor-mediated effects on motor hyperactivity in mice. ITI-333 alone is a naloxone-sensitive analgesic (mice) which suppresses somatic signs of naloxone-precipitated oxycodone withdrawal (mice) and heroin cue-induced reinstatement responding without apparent tolerance or physical dependence after chronic dosing (rats). ITI-333 did not acutely impair gastrointestinal or pulmonary function (rats) and was not intravenously self-administered by heroin-maintained rats or rhesus monkeys.
CONCLUSIONS
ITI-333 acts as a potent 5-HT receptor antagonist, as well a biased MOP receptor partial agonist with low intrinsic efficacy. ITI-333 mitigates opioid withdrawal/reinstatement, supporting its potential utility as a treatment for OUD.
Topics: Animals; Mice; Male; Substance Withdrawal Syndrome; Rats; Humans; Rats, Sprague-Dawley; Receptors, Opioid, mu; Serotonin 5-HT2 Receptor Antagonists; Substance-Related Disorders; Opioid-Related Disorders; Dose-Response Relationship, Drug; Oxycodone; Analgesics, Opioid; Self Administration; Cricetulus; CHO Cells
PubMed: 38710856
DOI: 10.1007/s00213-024-06578-w -
Neuropharmacology Aug 2024Opioid use disorder (OUD) is a chronic condition associated with long-lasting molecular and behavioral changes. Animals with prolonged access to opioids develop...
Opioid use disorder (OUD) is a chronic condition associated with long-lasting molecular and behavioral changes. Animals with prolonged access to opioids develop behaviors similar to human OUD. Identifying associated molecular changes can provide insight to underpinnings that lead to or maintain OUD. In pilot studies, we identified several miRNA targets that are altered by the administration of oxycodone. We selected mir182 for follow up as it was recently shown to be dysregulated in plasma of men administered oxycodone. In addition, mir182 is increased in reward-related brain regions of male rats following exposure to various addictive substances. The present study utilizes a long-access oxycodone self-administration paradigm to examine changes in mir182 and its mRNA targets associated with neuroplasticity, which may be involved in the maintenance of OUD-like phenotype in rats. Male rats were trained to self-administer oxycodone (0.1 mg/kg/infusion, i. v.) for 6 h daily sessions for 12 days. Each animal had a yoked saline control that received matched saline infusions. Animals were then tested on a progressive ratio schedule to measure motivation to obtain a single infusion of oxycodone. Drug seeking was measured following 28 days of forced abstinence using a 90-min cued/test. RTqPCR was utilized to measure mir182 and mRNA targets related to neuroplasticity (wnt3, plppr4, pou3f3, tle4, cacna2d, and bdnf) from the nucleus accumbens. Data revealed that animals responded on a continuum for oxycodone. When divided into two groups termed high- and low responders, animals diverged during self-administration acquisition and maintained differences in behavior and gene expression throughout the study. mir182 was upregulated in the nucleus accumbens of both high and low responders and negatively correlated with tle4, which showed a strong negative correlation with reinstatement behavior. mRNA target levels were correlated with behaviors associated with increased severity of OUD behavior in male rats.
Topics: Animals; Male; Oxycodone; Self Administration; Neuronal Plasticity; Rats; MicroRNAs; Individuality; Rats, Sprague-Dawley; Analgesics, Opioid; Opioid-Related Disorders; Nucleus Accumbens; Brain-Derived Neurotrophic Factor
PubMed: 38710443
DOI: 10.1016/j.neuropharm.2024.109972 -
Psychopharmacology May 2024
PubMed: 38709276
DOI: 10.1007/s00213-024-06605-w -
Scandinavian Journal of Pain Jan 2024Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Multimodal pain management is one component in enhanced recovery after surgery protocol. Here we evaluate the efficacy of tramadol-paracetamol in acute postoperative pain and pain outcome at 12 months after spine surgery in randomized, double-blind, placebo-controlled trial.
METHODS
We randomized 120 patients undergoing spine surgery to receive, for add-on pain management, two tramadol-paracetamol 37.5 mg/325 mg ( = 61) or placebo tablets ( = 59) twice a day for 5 postoperative days. In the hospital, multimodal pain management consisted of dexketoprofen and oxycodone. After discharge, patients were prescribed ibuprofen 200 mg, maximum 1,200 mg/day. Pain, analgesic use, and satisfaction with pain medication were followed up with the Brief Pain Inventory questionnaire before surgery and at 1 and 52 weeks after surgery. The primary outcome was patients' satisfaction with pain medication 1 week after surgery.
RESULTS
At 1 week after surgery, patients' satisfaction with pain medication was similarly high in the two groups, 75% [interquartile range, 30%] in the placebo group and 70% [40%] in the tramadol-paracetamol group ( = 0.949) on a scale: 0% = not satisfied, 100% = totally satisfied. At 1 week, ibuprofen dose was lower in the placebo group 200 mg [1,000] compared to the tramadol-paracetamol group, 800 mg [1,600] ( = 0.016). There was no difference in the need for rescue oxycodone. Patients in the tramadol-paracetamol group had more adverse events associated with analgesics during the first postoperative week (relative risk = 1.8, 95% confidence interval, 1.2-2.6).
CONCLUSION
Add-on pain treatment with tramadol-paracetamol did not enhance patients' satisfaction with early pain management after back surgery.
Topics: Humans; Pain, Postoperative; Tramadol; Double-Blind Method; Acetaminophen; Male; Female; Middle Aged; Analgesics, Opioid; Patient Satisfaction; Oxycodone; Analgesics, Non-Narcotic; Adult; Spine; Treatment Outcome; Ibuprofen; Pain Measurement; Aged
PubMed: 38708610
DOI: 10.1515/sjpain-2023-0105