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BMC Anesthesiology May 2023Management of acute postoperative pain is one of the major challenges in pediatric patients. Oral oxycodone has shown good pain relief in postoperative pain relief in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Management of acute postoperative pain is one of the major challenges in pediatric patients. Oral oxycodone has shown good pain relief in postoperative pain relief in children, but no studies have investigated intravenous oxycodone in this context.
OBJECTIVE
whether oxycodone PCIA can provide adequate and safe postoperative pain relief, in comparison to tramadol as reference opioid drug.
DESIGN
a randomized, double-blind, parallel, multi-center clinical trial.
SETTING
five university medical centers and three teaching hospitals in China.
PARTICIPANTS
patients aged 3-month-old to 6-year-old undergoing elective surgery under general anesthesia.
INTERVENTION
patients were randomly allocated to either tramadol (n = 109) or oxycodone (n = 89) as main postoperative opioid analgesic. Tramadol or oxycodone were administered with a loading dose at the end of surgery (1 or 0.1 mg.kg, respectively), then with a parent-controlled intravenous device with fixed bolus doses only (0.5 or 0.05 mg.kg-1, respectively), and a 10-min lockout time.
OUTCOMES
the primary outcome was adequate postoperative pain relief, defined as a face, legs, activity, cry, and consolability (FLACC) score < 4/10 in the post-anesthesia care unit (PACU), with no need for an alternative rescue analgesia. FLACC was measured 10 min after extubation then every 10 min until discharge from PACU. Analgesia was currently conducted with the boluses of either tramadol or oxycodone if FLACC was ≥ 3, up to three bolus doses, after what rescue alternative analgesia was administered.
RESULTS
tramadol and oxycodone provided a similar level of adequate postoperative pain relief in PACU and in the wards. No significant differences were either noted for the raw FLACC scores, the bolus dose demand in PACU, the time between the first bolus dose and discharge from PACU, analgesic drug consumption, bolus times required in the wards, function activity score, or the parents' satisfaction. The main observed side effects in both groups were nausea and vomiting, with no difference between groups. However, patients in the oxycodone group showed less sedation levels and had a shorter stay in the PACU, compared with the tramadol group.
CONCLUSIONS
an adequate postoperative analgesia can be achieved with intravenous oxycodone, this with less side effects than tramadol. It can therefore be a choice for postoperative pain relief in pediatric patients.
TRIAL REGISTRATION
The study was registered at www.chictr.org.cn (Registration number: ChiCTR1800016372; date of first registration: 28/05/2018; updated date:06/01/2023).
Topics: Humans; Child; Infant; Tramadol; Oxycodone; Prospective Studies; Analgesia, Patient-Controlled; Analgesics, Opioid; Pain, Postoperative; Double-Blind Method
PubMed: 37138225
DOI: 10.1186/s12871-023-02054-8 -
Addiction (Abingdon, England) Sep 2021To establish and quantify the association between abuse-deterrent formulation (ADF) oxycodone and 1-year risk of opioid-related harm.
AIM
To establish and quantify the association between abuse-deterrent formulation (ADF) oxycodone and 1-year risk of opioid-related harm.
DESIGN
Propensity score-matched cohort study of electronic medical records for years 2014-18, with patients followed up for 1 year after their index health-care visit.
SETTING
More than 70 million patients from 56 US health-care organizations.
PARTICIPANTS
Patients aged 18-64 years at index health-care visit with any indication for an oral opioid analgesic, with no past 12-month history of oral oxycodone use or substance use disorder, and who were alive at the end of the 1-year follow-up (new episode of prescription oral ADF oxycodone [OxyContin], n = 45 045; new episode of non-ADF oxycodone opioid preparation, n = 1 377 359).
MEASUREMENTS
International Classification of Diseases diagnoses of any opioid-related disorder or non-fatal opioid poisoning within 1 year of the index health-care visit. Pooled odds ratios (OR) with 95% confidence intervals (95% CI).
FINDINGS
After propensity score matching, 89 802 patients with a mean age of 44 [standard deviation (SD) = 11] years (62% women, 68% white) were included. During 1-year follow-up, 1445 diagnoses of opioid use disorder or opioid poisoning occurred in the ADF oxycodone cohort (34.8/1000 person-years) and 765 occurred in the non-ADF oxycodone cohort (18.2/1000 person-years). The odds of opioid-related adverse outcomes were increased in the ADF oxycodone cohort compared with the non-ADF oxycodone opioid cohort, including for opioid use disorders (OR = 2.02; 95% CI = 1.83, 2.23) and opioid poisoning (OR = 1.64 95% CI = 1.35, 1.99).
CONCLUSIONS
Patients with a new prescription of abuse-deterrent formulation oxycodone may be at increased risk of opioid-related harm.
Topics: Analgesics, Opioid; Child; Cohort Studies; Delayed-Action Preparations; Electronic Health Records; Female; Humans; Male; Opioid-Related Disorders; Oxycodone
PubMed: 33394528
DOI: 10.1111/add.15392 -
Psychopharmacology Dec 2022Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like...
RATIONALE
Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like decoctions, and commercial extracts are taken orally, primarily for health and well-being by millions of people globally. Others take kratom to eliminate opioid use for analgesia and manage opioid withdrawal and use disorder. There is debate over the possible respiratory depressant overdose risk of the primary active alkaloid, mitragynine, a partial μ-opioid receptor agonist, that does not signal through ß-arrestin, the primary opioid respiratory depressant pathway.
OBJECTIVES
Compare the respiratory effects of oral mitragynine to oral oxycodone in rats with the study design previously published by US Food and Drug Administration (FDA) scientists for evaluating the respiratory effects of opioids (Xu et al., Toxicol Rep 7:188-197, 2020).
METHODS
Blood gases, observable signs, and mitragynine pharmacokinetics were assessed for 12 h after 20, 40, 80, 240, and 400 mg/kg oral mitragynine isolate and 6.75, 60, and 150 mg/kg oral oxycodone hydrochloride.
FINDINGS
Oxycodone administration produced significant dose-related respiratory depressant effects and pronounced sedation with one death each at 60 and 150 mg/kg. Mitragynine did not yield significant dose-related respiratory depressant or life-threatening effects. Sedative-like effects, milder than produced by oxycodone, were evident at the highest mitragynine dose. Maximum oxycodone and mitragynine plasma concentrations were dose related.
CONCLUSIONS
Consistent with mitragynine's pharmacology that includes partial µ-opioid receptor agonism with little recruitment of the respiratory depressant activating β-arrestin pathway, mitragynine produced no evidence of respiratory depression at doses many times higher than known to be taken by humans.
Topics: Animals; Rats; Analgesics, Opioid; Mitragyna; Oxycodone; Plant Extracts; Receptors, Opioid; Secologanin Tryptamine Alkaloids
PubMed: 36308562
DOI: 10.1007/s00213-022-06244-z -
Journal of Neuroimaging : Official... Sep 2021The changes in functional brain connectivity induced by treatment with analgesics are poorly investigated. Unfortunately, results from clinical studies investigating... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND PURPOSE
The changes in functional brain connectivity induced by treatment with analgesics are poorly investigated. Unfortunately, results from clinical studies investigating treatments in patients with pain are often confounded by co-medication and comorbidity. Thalamus is central in sensory processing, and we hypothesized that functional connectivity between thalamus and other brain areas in healthy volunteers was different in treatment with oxycodone, representing a pure opioid, compared to treatment with tapentadol, which has a dual effect on the opioidergic and adrenergic systems.
METHODS
Twenty-one healthy male volunteers were included in a randomized, double-blind, three-armed, placebo-controlled, cross-over study. All received tapentadol (50 mg extended release), oxycodone (10 mg extended release), or placebo twice daily for 14 days. Resting-state functional magnetic resonance imaging data were obtained before and after treatment. Seed-based functional connectivity analyses were performed between thalamus and other brain regions.
RESULTS
Compared to placebo, tapentadol increased functional connectivity between left thalamus and precentral cortex (P = .048), whereas oxycodone decreased functional connectivity between bilateral thalamus and the anterior cingulate cortex (P ≤ .005).
CONCLUSIONS
This study has shown that the functional connectivity between thalamus and other brain areas central in pain processing was different for the tapentadol and oxycodone treatments compared to placebo. This supports that the two treatments exert different mechanism of action. Further studies with larger sample sizes need to be carried out in order to validate this.
Topics: Analgesics, Opioid; Brain; Cross-Over Studies; Double-Blind Method; Humans; Male; Oxycodone; Phenols; Tapentadol
PubMed: 34196442
DOI: 10.1111/jon.12902 -
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 -
BMC Anesthesiology Oct 2021Angiogenesis, the formation of blood vessel from pre-existing ones, plays an important role in many pathophysiological diseases, such as cancer. Opioids are often used... (Comparative Study)
Comparative Study
BACKGROUND
Angiogenesis, the formation of blood vessel from pre-existing ones, plays an important role in many pathophysiological diseases, such as cancer. Opioids are often used in clinic for the management of chronic pain in cancer patients at terminal phases. Here, we investigated and compared the effects and mechanisms of four opioids on angiogenesis.
METHODS
We performed angiogenesis assays on human umbilical vein endothelial cells (HUVEC) that represent an in vitro model to assess the toxicity of drugs to endothelium.
RESULTS
Morphine and oxycodone at 0.1 μM to 100 μM dose-dependently increased endothelial cell tube formation and proliferation. We observed the same in endothelial cells exposed to fentanyl at 0.1 μM to 10 μM but there was a gradual loss of stimulation by fentanyl at 100 μM and 1000 μM. Morphine and fentanyl reduced endothelial cell apoptosis-induced by serum withdrawal whereas oxycodone did not display anti-apoptotic effect, via decreasing Bax level. Oxycodone at the same concentrations was less potent than morphine and fentanyl. Different from other three opioids, codeine at all tested concentrations did not affect endothelial cell tube formation, proliferation and survival. Mechanism studies demonstrated that opioids acted on endothelial cells via μ-opioid receptor-independent pathway. Although we observed the increased phosphorylation of mitogen-activated protein kinase (MAPK) in cells exposed to morphine, fentanyl and oxycodone, the rescue studies demonstrated that the stimulatory effects of morphine but not fentanyl nor oxycodone were reversed by a specific MAPK inhibitor.
CONCLUSION
Our work demonstrates the differential effects and mechanisms of opioids on angiogenesis.
Topics: Analgesics, Opioid; Cell Proliferation; Cells, Cultured; Endothelial Cells; Fentanyl; Humans; Mitogen-Activated Protein Kinases; Morphine; Neovascularization, Physiologic; Oxycodone; Phosphorylation; Umbilical Veins
PubMed: 34702181
DOI: 10.1186/s12871-021-01475-7 -
Psychopharmacology Oct 2022Although polysubstance use is highly prevalent, preclinical studies that assess voluntary consumption of multiple substances at the same time are rather uncommon....
RATIONALE
Although polysubstance use is highly prevalent, preclinical studies that assess voluntary consumption of multiple substances at the same time are rather uncommon. Overlooking drug taking patterns commonly observed in humans may limit the translational value of preclinical models.
OBJECTIVES
Here, we aimed to develop a model of polysubstance use that could be used to assess oral operant self-administration patterns under concurrent access to alcohol and the prescription opioid oxycodone.
METHODS
After a training period where animals associated specific cues and levers with each drug, rats self-administered alcohol and oxycodone solutions concurrently in daily sessions. Oxycodone was then removed to assess potential changes in alcohol consumption. The role of cues and stress on alcohol consumption and oxycodone seeking was also examined under reinstatement conditions.
RESULTS
We found that females consumed more alcohol and oxycodone than males when given access to both drugs, and this effect on alcohol intake persisted when oxycodone was removed. Additionally, re-exposure to oxycodone cues in combination with the administration of the pharmacological stressor yohimbine drove reinstatement of oxycodone seeking in females but did not have a strong effect in males, possibly due to low levels of oxycodone intake during active self-administration in male rats. Additionally, yohimbine drove increased alcohol consumption, in line with prior findings from our group and others.
CONCLUSIONS
Taken together, this study demonstrates that rats will concurrently self-administer both oxycodone and alcohol in operant chambers, and this procedure can serve as a platform for future investigations in polysubstance use and relapse-like behavior.
Topics: Analgesics, Opioid; Animals; Conditioning, Operant; Ethanol; Extinction, Psychological; Female; Humans; Male; Oxycodone; Rats; Self Administration; Yohimbine
PubMed: 35972517
DOI: 10.1007/s00213-022-06210-9 -
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 -
Chemico-biological Interactions Sep 2022Cancer patients experience pain during medical treatment. Therefore, anticancer drugs and painkillers are often prescribed together. This study aims to determine the...
PURPOSE
Cancer patients experience pain during medical treatment. Therefore, anticancer drugs and painkillers are often prescribed together. This study aims to determine the interaction between anlotinib and oxycodone and reveal the underlying mechanism.
METHODS
UPLC-MS/MS, an efficient and sensitive method, was used for the simultaneous determination of oxycodone and oxycodone metabolites. Sprague-Dawley rats were given oxycodone with or without anlotinib. Then, UPLC-MS/MS was used to determine the blood concentration of oxycodone. To study the interaction mechanism, rat and human liver microsomes (HLMs) were used for determining enzyme kinetics.
RESULTS
Long-term administration of oxycodone combined with anlotinib resulted in significantly increased pharmacokinetic parameters AUC, AUC, and C for oxycodone, indicating that anlotinib inhibited oxycodone. In vitro kinetic measurements indicated that anlotinib inhibited the metabolism of oxycodone through a mixed mechanism. Further studies indicated that in HLMs, anlotinib strongly inhibited the metabolism of oxycodone.
CONCLUSION
This study showed that anlotinib inhibited the metabolism of oxycodone both in vitro and in vivo. It is recommended that the dose of oxycodone should be reconsidered when oxycodone is combined with anlotinib in clinical practice.
Topics: Animals; Chromatography, Liquid; Humans; Indoles; Oxycodone; Quinolines; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry
PubMed: 35853539
DOI: 10.1016/j.cbi.2022.110044 -
Journal of the Chinese Medical... May 2022Opioids are effective for severe pain; however, the safety issue is also a primary concern. To better understand the opioid use in Taiwan, we conducted this study.
BACKGROUND
Opioids are effective for severe pain; however, the safety issue is also a primary concern. To better understand the opioid use in Taiwan, we conducted this study.
METHODS
Data on patients with opioid prescriptions, including morphine, fentanyl, pethidine, codeine, oxycodone, hydromorphone, and buprenorphine were collected using the Taiwan National Health Insurance Database (NHID).
RESULTS
Our analysis of opioid prescriptions from 2008 to 2018 in Taiwan indicated that (1) A slow increase in prevalence of opioid prescription was found during the study period. Among the drugs studied, morphine accounted for the majority of the prescriptions written, with a gradual increase annually. Pethidine prescriptions showed a significant and rapid decline over the years; (2) medical centers prescribed the largest number of opioids, followed by regional hospitals, local hospitals, and clinics; (3) the number of prescriptions per year per capita in cancer group was much higher than that in noncancer group. In noncancer group, most of the prescriptions were used in acute pain service (98.7%); and (4) use of opioids increased with age in both cancer and noncancer patients.
CONCLUSION
The total number of opioid prescriptions in Taiwan gradually increased annually, among which morphine was the most commonly used opioid. Cancer patients consumed more opioid prescriptions than noncancer patients and most of the prescriptions in noncancer patients were used in acute pain service. The number of prescriptions increased with the age of the patients in both cancer and noncancer patients. The low prescription rate of opioids in chronic pain in Taiwan is not similar as those in high opioid-consuming countries, such as United States.
Topics: Analgesics, Opioid; Chronic Pain; Drug Prescriptions; Humans; Meperidine; Morphine; Neoplasms; Oxycodone; Prevalence; Taiwan; United States
PubMed: 35353736
DOI: 10.1097/JCMA.0000000000000720