Intravenous Oxycodone Research Articles

Alternative Reinforcers Enhance the Effects of Opioid Antagonists, but Not Agonists, on Oxycodone Choice Self-Administration in Nonhuman Primates.

Clinical reports suggest that the most effective strategies for managing opioid use disorder comprise a comprehensive treatment program of both pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective are not well characterized. This study examined whether the presence of an alternative reinforcer could alter the efficacy of Food and Drug Administration-approved opioid antagonist or agonist medications, as well as the nonopioid flumazenil, in decreasing oxycodone choice self-administration in nonhuman primates. Adult squirrel monkeys (n = 7; four females) responded under concurrent second-order fixed-ratio (FR)-3(FR5:S);TO45s schedules of reinforcement for intravenous oxycodone (0.1 mg/kg) or saline on one lever and 30% sweetened condensed milk or water on the other. Doses of naltrexone (0.00032-1.0 mg/kg), nalbuphine (0.32-10 mg/kg), buprenorphine (0.0032-0.032 mg/kg), methadone (0.32-1.0 mg/kg), or flumazenil (1-3.2 mg/kg) were administered intramuscularly prior to oxycodone self-administration sessions that occurred with either milk or water as the alternative. Naltrexone, a μ-opioid receptor antagonist, was >30-fold more potent when milk was available compared with water and abolished oxycodone intake (injections/session) while concomitantly increasing milk deliveries at the highest dose tested. Pretreatment with the low-efficacy μ-agonist nalbuphine was most effective in the presence of milk compared with water, decreasing oxycodone preference to <50% of control values. The higher efficacy μ-agonists, methadone and buprenorphine, and the benzodiazepine antagonist flumazenil did not appreciably alter the reinforcing potency of oxycodone under either condition. These results suggest that antagonist medications used in combination with alternative reinforcers may be an effective strategy to curtail opioid abuse-related behaviors. SIGNIFICANCE STATEMENT: Clinical treatment programs for opioid use disorder use a combination of pharmacological and nonpharmacological approaches. However, the conditions under which these combinations are most effective have not been fully characterized. This study examined whether the effectiveness of μ-opioid medications to decrease oxycodone self-administration is altered in the presence of an alternative reinforcer. The results suggest that alternative reinforcers enhance the effects of antagonist or low-efficacy partial agonists, suggesting they may be a more effective strategy to curtail opioid use.

Neuropathic pain has sex-specific effects on oxycodone-seeking and non-drug-seeking ensemble neurons in the dorsomedial prefrontal cortex of mice.

Approximately 50 million Americans suffer from chronic pain, and nearly a quarter of chronic pain patients have reported misusing opioid prescriptions. Repeated drug seeking is associated with reactivation of an ensemble of neurons sparsely scattered throughout the dorsomedial prefrontal cortex (dmPFC). Prior research has demonstrated that chronic pain increases intrinsic excitability of dmPFC neurons, which may increase the likelihood of reactivation during drug seeking. We tested the hypothesis that chronic pain would increase oxycodone-seeking behaviour and that the pain state would differentially increase intrinsic excitability in dmPFC drug-seeking ensemble neurons. TetTag mice self-administered intravenous oxycodone. After 7days of forced abstinence, a drug-seeking session was performed, and the ensemble was tagged. Mice received spared nerve injury (SNI) to induce chronic pain during the period between the first and second seeking session. Following the second seeking session, we performed electrophysiology on individual neurons within the dmPFC to assess intrinsic excitability of the drug-seeking ensemble and non-ensemble neurons. SNI had no impact on sucrose seeking or intrinsic excitability of dmPFC neurons from these mice. In females, SNI increased oxycodone seeking and intrinsic excitability of non-ensemble neurons. In males, SNI had no impact on oxycodone seeking or neuron excitability. Data from females are consistent with clinical reports that chronic pain can promote drug craving and relapse and support the hypothesis that chronic pain itself may lead to neuroadaptations which promote opioid seeking.

Effects of popliteal plexus block after total knee arthroplasty: a randomized clinical trial

Background and objectivesMotor-sparing peripheral nerve blocks enhance multimodal opioid-sparing strategies after total knee arthroplasty. We hypothesized that adding a popliteal plexus block to a femoral triangle block could reduce 24-hour...

Assessment of feasibility of opioid-free anesthesia combined with preoperative thoracic paravertebral block and postoperative intravenous patient-controlled analgesia oxycodone with non-opioid analgesics in the perioperative anesthetic management for video-assisted thoracic surgery.

This study, conducted between December 2015 and March 2018 at a single university hospital, explored the feasibility and safety of opioid-free anesthesia combined with preoperative thoracic paravertebral block (ThPVB) for patients undergoing elective video-assisted thoracoscopic surgery (VATS). The aim was to assess the impact of this approach on postoperative pain levels and opioid consumption. Sixty-four patients scheduled for elective VATS were randomly assigned to either the intervention group, receiving opioid-free anesthesia with ThPVB, or the control group, managed with standard general anesthesia. Postoperatively, both groups received oxycodone patient-controlled analgesia along with non-opioid analgesics. Pain intensity was measured using the Numeric Pain Rating Scale (NRS) and Prince Henry Hospital Pain Score (PHHPS). The total dose of postoperative oxycodone and the occurrence of opioid-related adverse events were recorded during the 24-hour follow-up period. Patients in the intervention group showed significantly lower pain levels at 20 and 24 hours post-procedure ( P = 0.015, P = 0.021, respectively) compared to the control group. Notably, oxycodone consumption at 24 hours was significantly higher in the control group ( p < 0.0001). No serious adverse events were observed during the study period. This study demonstrates the feasibility and safety of opioid-free anesthesia combined with ThPVB for elective VATS. The approach significantly reduces postoperative pain and the need for opioids, supporting its potential as an effective and balanced perioperative anesthetic strategy.

Voluntary alcohol intake alters the motivation to seek intravenous oxycodone and neuronal activation during the reinstatement of oxycodone and sucrose seeking

Opioid-alcohol polysubstance use is prevalent and worsens treatment outcomes. Here we assessed whether co-consumption of oxycodone and alcohol influence the intake of one another, demand for oxycodone, and the neurocircuitry underlying cue-primed reinstatement of oxycodone-seeking. Male and female rats underwent oxycodone intravenous self-administration (IVSA) with homecage access to alcohol (20% v/v) and/or water immediately after the IVSA session. Next, economic demand for intravenous oxycodone was assessed while access to alcohol and/or water continued. Control rats self-administered sucrose followed by access to alcohol and/or water. Rats underwent a cue-primed reinstatement test and brains were processed for c-fos mRNA expression. While both sexes decreased oxycodone intake if they had access to alcohol, and decreased alcohol intake if they had access to oxycodone, only female oxycodone + alcohol rats exhibited decreased demand elasticity and increased cue-primed reinstatement. Alcohol consumption increased the number of basolateral and central amygdala neurons activated during sucrose and oxycodone reinstatement and the number of ventral and dorsal striatum neurons engaged by sucrose reinstatement. Nucleus accumbens shell dopamine 1 receptor expressing neurons displayed activation patterns consistent with oxycodone reinstatement. Thus, alcohol alters the motivation to seek oxycodone in a sex-dependent manner and the neural circuitry engaged by cue-primed reinstatement of sucrose and oxycodone-seeking.

A new formulation of dezocine, Cyc-dezocine, reduces oxycodone self-administration in female and male rats

Dezocine is a partial mu opioid receptor agonist previously used as an analgesic for perioperative acute pain in the US and is now the most used perioperative analgesic in China. In general, dezocine is well-tolerated, with relatively minimal risk of fatal respiratory depression. To our knowledge, there are no reports of dezocine addiction, which suggests that the abuse liability of dezocine is low. The overarching goal of this study was to determine the efficacy of a novel formulation of dezocine (Cyc-dezocine), developed for intraperitoneal or intranasal administration, to reduce voluntary opioid taking in rats. One cohort of male rats self-administered intravenous oxycodone on a fixed-ratio 5 schedule of reinforcement. Once oxycodone taking stabilized, rats were pretreated with systemic injections of vehicle or Cyc-dezocine. Cyc-dezocine dose-dependently reduced intravenous oxycodone self-administration. A second cohort of male and female rats self-administered oral oxycodone from drinking water. Once oxycodone taking stabilized, rats were pretreated with intra-nasal Cyc-dezocine. Consistent with the effects of i.p. Cyc-dezocine in our intravenous oxycodone studies, intra-nasal Cyc-dezocine attenuated oral oxycodone self-administration. Together, these findings support the need for further studies investigating the therapeutic potential of Cyc-dezocine for treating opioid use disorder.

Effects of sex and estrous cycle on intravenous oxycodone self-administration and the reinstatement of oxycodone-seeking behavior in rats.

The increasing misuse of both prescription and illicit opioids has culminated in a national healthcare crisis in the United States. Oxycodone is among the most widely prescribed and misused opioid pain relievers and has been associated with a high risk for transition to compulsive opioid use. Here, we sought to examine potential sex differences and estrous cycle-dependent effects on the reinforcing efficacy of oxycodone, as well as on stress-induced or cue-induced oxycodone-seeking behavior, using intravenous (IV) oxycodone self-administration and reinstatement procedures. In experiment 1, adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone according to a fixed-ratio 1 schedule of reinforcement in daily 2-h sessions, and a dose-response function was subsequently determined (0.003-0.03 mg/kg/inf). In experiment 2, a separate group of adult male and female Long-Evans rats were trained to self-administer 0.03 mg/kg/inf oxycodone for 8 sessions, followed by 0.01 mg/kg/inf oxycodone for 10 sessions. Responding was then extinguished, followed by sequential footshock-induced and cue-induced reinstatement tests. In the dose-response experiment, oxycodone produced a typical inverted U-shape function with 0.01 mg/kg/inf representing the maximally effective dose in both sexes. No sex differences were detected in the reinforcing efficacy of oxycodone. In the second experiment, the reinforcing effects of 0.01-0.03 mg//kg/inf oxycodone were significantly attenuated in females during proestrus/estrus as compared to metestrus/diestrus phases of the estrous cycle. Neither males nor females displayed significant footshock-induced reinstatement of oxycodone seeking, but both sexes exhibited significant cue-induced reinstatement of oxycodone seeking at magnitudes that did not differ either by sex or by estrous cycle phase. These results confirm and extend previous work suggesting that sex does not robustly influence the primary reinforcing effects of oxycodone nor the reinstatement of oxycodone-seeking behavior. However, our findings reveal for the first time that the reinforcing efficacy of IV oxycodone varies across the estrous cycle in female rats.

Oxycodone does not affect placental circulatory physiology during the early first stage of labor-A randomized trial.

Opioids are used for pain relief during the first stage of labor. Oxycodone can cause maternal hypotension that may modify utero- and fetoplacental circulatory physiology. We hypothesized that maternal intravenous (i.v.) oxycodone has no detrimental effect on utero- and fetoplacental hemodynamics during the early first stage of labor. Twenty-two parturients requiring pain relief during the first stage of labor were randomized in a double-blinded and placebo-controlled study. By Doppler ultrasonography, both uterine artery (Ut) and umbilical vein (UV) volume blood flows (Q), Ut pulsatility index (PI), and Ut vascular resistance (RUt) were calculated. Blood flow velocity waveforms were obtained between uterine contractions. After baseline measurements, women received oxycodone 0.05 mg/kg or a placebo intravenous. Doppler ultrasonography was repeated up to 120 min after the first drug administration. The second dose of oxycodone 0.05 mg/kg was allowed at 60 min to all parturients with contraction pain ≥5/10. Maternal plasma samples were collected at each study phase and after delivery with umbilical cord plasma samples, to measure oxycodone concentrations. gov identifier (NCT no. NCT02573831). At baseline, mean QUt and QUV did not differ significantly between the placebo-first (478 mL/min and 57 mL/min/kg) and the oxycodone-first (561 mL/min and 71 mL/min/kg) groups. In addition, RUt and Ut PI were comparable between the groups. Following oxycodone at 60 min, mean QUt and QUV (714 mL/min and 52 mL/min/kg) were similar to the placebo-first (520 mL/min and 55 mL/min/kg) group. Furthermore, all the measured parameters were comparable to the baseline values. At 60 min after the first study drug administration, all the parturients in the placebo-first group needed intravenous oxycodone 0.05 mg/kg. At 120 min, we found no statistically significant change in any of the measured parameters. No significant correlation was found between maternal oxycodone concentration and QUt or QUV. Furthermore, newborn oxycodone concentration did not correlate with QUV. Oxycodone did not have any detrimental effect on either utero- or fetoplacental circulatory physiology during the early first stage of labor. Maternal plasma oxycodone did not correlate with utero- and fetoplacental hemodynamics. No correlation was found between newborn oxycodone concentration and fetoplacental hemodynamics.

Strain and sex-related behavioral variability of oxycodone dependence in rats

Over the past two decades, the escalating prescription of opioid medications for pain management has culminated in a widespread opioid epidemic, significantly impacting public health, social dynamics, and economic stability. The urgent need for improved treatments for opioid addiction necessitates a deeper understanding of its biological underpinnings, with genetic variations playing a crucial role in individual susceptibility to opioid use disorder (OUD) and influencing clinical practices.In this study, we leverage the genetic diversity of four rat strains (ACI/N, BN/NHsd, WKY/N, and F344/N) to examine the contribution of genetic factors to oxycodone metabolism and addiction-like behaviors. We used the extended access to intravenous oxycodone self-administration procedure (12 h/day, 0.15 mg/kg/injection) to comprehensively characterize oxycodone-related behaviors and pharmacokinetics. We measured escalation of oxycodone self-administration, motivation for drug consumption, tolerance to the analgesic effects of oxycodone, withdrawal-induced hyperalgesia, and oxycodone-induced respiratory depression. Additionally, we examined oxycodone-seeking behavior after four weeks of withdrawal by reintroducing the animals to environmental and cue stimuli previously associated with oxycodone self-administration.The findings revealed notable strain differences in several behavioral measures, including oxycodone metabolism. Intriguingly, BN/NHsd and WKY/N strains exhibited similar drug intake and escalation patterns but displayed significant disparities in oxycodone and oxymorphone metabolism. Minimal sex differences were observed within strains, primarily relating to oxycodone metabolism.In conclusion, this study identifies strain differences in the behavioral responses and pharmacokinetics associated with oxycodone self-administration in rats, providing a robust foundation for identifying genetic and molecular variants associated with various facets of the opioid addiction process.

Oxycodone vs. tramadol in postoperative parent-controlled intravenous analgesia in children: a prospective, randomized, double-blinded, multiple-center clinical trial

BackgroundManagement 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.Objectivewhether oxycodone PCIA can provide adequate and safe postoperative pain relief, in comparison to tramadol as reference opioid drug.Designa randomized, double-blind, parallel, multi-center clinical trial.Settingfive university medical centers and three teaching hospitals in China.Participantspatients aged 3-month-old to 6-year-old undergoing elective surgery under general anesthesia.Interventionpatients 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–1, 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.Outcomesthe 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.Resultstramadol 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.Conclusionsan 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 registrationThe study was registered at www.chictr.org.cn (Registration number: ChiCTR1800016372; date of first registration: 28/05/2018; updated date:06/01/2023).

Rapid Titration With Intravenous Oxycodone for Severe Cancer Pain and Oral Conversion Ratio.

to assess a dose titration with intravenous oxycodone to achieve rapid pain relief of cancer pain of severe intensity. The second objective was to provide a conversion ratio with the oral route. Cancer patients admitted for severe pain were prospectively assessed. At admission (T0) previous opioid doses were recorded. Edmonton symptom assessment scale (ESAS) was collected from T0 until the conclusion of the observation. Intravenous boluses of oxycodone were given until the initial signs of significant analgesia were detected. The effective dose was multiplied for six and given as intravenous continuous infusion. When the patient was considered stabilized the intravenous daily dose was converted to oral oxycodone using an initial ratio of 1:2. Subsequently, doses of oral oxycodone were changed according to the clinical situation. Twenty-nine patients were examined. A mean effective bolus dose of oxycodone was 9.5 mg (SD 8.0) allowed to achieve a meaningful pain relief in a mean of 10.4 minutes (SD 3.3). The mean initial and the final infusion doses were 51.0 mg/day (standard deviation 40.9) and 69.7 mg/day ( standard deviation76.6), respectively. A significant change in pain intensity was observed at the different time intervals (P<0.0005). Conversion to oral route occurred after a mean of 2.7 days (standard deviation1.2) of intravenous oxycodone. The final mean conversion ratio was 1:2,12 ( standard deviation0.36). Rapid intravenous oxycodone dose titration resulted in rapid pain relief. The intravenous-oral conversion ratio of 1:2 is reliable. Further studies are necessary to confirm this preliminary observation.

Postoperative Pain Management Total Hysterectomy with Intravenous Patient-Controlled Analgesia Oxycodone: A Case Series

Introduction: Patient-controlled analgesia (PCA) with intravenous opioids is a more efficient method to achieve better postoperative analgesia. This study aims to describe the use of patient-control analgesia in post-hysterectomy patients.&#x0D; Case presentation: There were two total hysterectomy postoperative patients who used PCA as postoperative pain management. Postoperatively, the first patient has given paracetamol tablets 500 mg every 6 hours orally, a santagesic 1 gram every 8 hours intravenously, and oxycodone intravenously with PCA. The second patient was given paracetamol tab 1 gram every 8 hours intravenously, analgesics 1 gram every 8 hours intravenously, and PCA intravenous oxycodone. Both patients felt the effectiveness of PCA as postoperative pain management.&#x0D; Conclusion: Multimodal analgesia or balanced analgesia is one method of managing acute postoperative pain. The success of using PCA is very much determined by the knowledge of the patient and the pain management team on PCA tools. Oxycodone provides fairly good analgesia with minimal side effects.

Population Pharmacokinetics and Dosing Simulations of Intravenous Oxycodone for Perioperative Pain Relief in Adult Surgical Patients with Obesity.

Oxycodone, a semisynthetic thebaine derivative µ-opioid (MOP) receptor agonist, is effective for treating moderate and severe pain in different clinical conditions. The pharmacokinetics of intravenous oxycodone in the obese population has not been studied. This study aims to characterize the pharmacokinetic profile of oxycodone after intravenous administration and to simulate an appropriate dosage for analgesic efficacy in obese patients. We recruited 33 (age range from 21 to 72 years) adult patients with a body mass index of 30 kg/m2and above, who were scheduled for non-cardiac surgeries. Intravenous oxycodone was administered after induction of general anesthesia and blood samples were collected up to 24 h after oxycodone administration.Plasma concentrations of oxycodone were assayed using liquid chromatography-tandem mass spectrometry and 253 concentration-time points were used for pharmacokinetic analysis using nonlinear mixed-effects modeling. Intravenous oxycodone pharmacokinetics were well described by a two-compartment open model. The estimated total clearance and central volume of distribution of oxycodone are 28.5 l/h per 70 kg and 56.4 l per 70 kg, respectively. Total body weight was identified as a significant covariate of the clearance and central volume of distribution. Dosing simulations based on the final model demonstrate that a starting dose of 0.10 mg/kg of intravenous oxycodone is adequate to achieve a target plasma concentration and repeated doses of 0.02 mg/kg may be administered at 1.5-h intervals to maintain a plasma concentration within an effective analgesic range. A population pharmacokinetic model using total body weight as a covariate supports the administration of 0.10 mg/kg of intravenous oxycodone as a starting dose and repeated doses of 0.02 mg/kg at 1.5-h intervals to maintain targeted plasma concentrations for analgesia in the obese adult population.

The effect of opioid-sparing anesthesia regimen on short-term cognitive function after thoracoscopic surgery: a prospective cohort study

BackgroundAs type of surgery and opioids are suggested risk factors for the development of cognitive decline after surgery, we evaluated the effect of an opioid-sparing anesthesia regimen involving preoperative erector spinae block and continuous infusion of flurbiprofen on the incidence of cognitive decline after video-assisted thoracoscopic surgery.MethodsIn this observational study, patients over 18 years old presenting for elective video-assisted thoracoscopic surgery were divided into two groups, the erector spinae plane block group (ESPB group, who received preoperative single shot of bi-level ESPB at T4 and T6 levels) and the control group who received intercostal nerve blocks through T5 to T7 intercostal spaces along mid-axillary line after surgery. Continuous infusion of flurbiprofen (8 mg/h) and intravenous oxycodone rescue (1 mg/bolus, lockout time 10 minutes) were provided as postoperative analgesics. Cognitive function was measured one day before and 48 h after surgery with brief Cogstate computerized battery (CCB).ResultsThere were 60 patients included with 30 in each group. Perioperative sufentanil dose was significantly reduced in ESPB group. Nine (30%) and 15 (50%) patients had delayed neurocognitive recovery in the ESPB group and the control group respectively. Psychomotor speed and visual attention tests were the two tests that patients showed cognitive decline. The results of multivariate regression revealed that patients who were more than 53.5 years of age (OR 9.213, 95% CI 1.789, 47.437, P = 0.008) and low levels of education (less than 9 years of complimentary education) (OR 6.829, 95% CI 1.068, 43.677, P = 0.042) were independent risk factors for postoperative delayed neurocognitive recovery. For subgroup analysis, ESPB could reduce the occurrence of delayed neurocognitive recovery in patients with both risk factors (6/10 (60%) vs. 11/11 (100%), P = 0.004) compared to the control group.ConclusionsMiddle-aged people and low levels of education are independent risk factors for delayed neurocognitive recovery after thoracoscopic surgery. ESPB has the potential to prevent cognitive decline in high-risk patients.Trial registrationChiCTR1800014508 (www.chictr.org.cn, January 17, 2018; Hong Zhao, M.D.). URL: http://www.chictr.org.cn/showproj.aspx?proj=24778. The date of the enrolment of the first participant to the trial was January 22, 2018.

Comparison of a Small Dose of Oxycodone and Sufentanil for the Prevention of Sufentanil-Induced Cough during General Anesthesia Induction: A Prospective Randomized Controlled Trial.

Background Sufentanil is widely used during anesthesia induction. However, it can cause coughing via different mechanisms. This study is aimed at evaluating the effectiveness of a small dose of oxycodone and sufentanil in suppressing sufentanil-induced cough (SIC) during general anesthesia induction. Methods Of the 174 patients scheduled for elective surgery, 144 were eligible and randomly divided into 3 groups (n = 48). Five minutes before sufentanil bolus (0.4 μg/kg), patients in group O received 0.02 mg/kg oxycodone intravenously within 5 s, those in group S received 0.02 μg/kg sufentanil within 5 s, and those in group N received an equal volume of 0.9% normal saline within 5 s. Sufentanil was diluted to 5 μg/ml and administered within 5 s after pretreatment. The incidence and severity of cough in the three groups were evaluated within 1 minute after sufentanil injection during the anesthesia induction. Their mean arterial pressure (MAP) and heart rate (HR) were recorded at T0 (after entering the operation), T1 (3 minutes after pretreatment), T2 (before intubation), and T3 (1 minute after intubation). Results The incidences of cough in group N, group O, and group S were 20 (41.6%), 7 (14.5%), and 6 (12.5%), respectively. Compared with group N, patients from group O and group S exhibited significantly reduced incidence and severity of cough, and the severity of cough in group O and group S was significantly reduced compared with group N (P < 0.05). No significant differences in the rangeability of MAP and HR were noted at the four time points in the three groups (P > 0.05). Conclusion. Preconditioning using intravenous oxycodone (0.02 mg/kg) or sufentanil (0.02 μg/kg) could represent an effective approach to reducing SIC in anesthesia induction and was associated with relatively stable hemodynamic state during general anesthesia. This trial is registered at Chinese Clinical Trial Registry with registration number ChiCTR1900021087.

Ultrasound-guided posterior quadratus lumborum block for postoperative pain control after minimally invasive radical prostatectomy: a randomized, double-blind, placebo-controlled trial.

A minimally invasive approach to radical prostatectomy offers improved ambulation and discharge times. Postoperative pain control is one of the key factors that facilitates rapid recovery. With the aim to assure adequate analgesia and minimize the use of opioids, application of truncal nerve blocks has been proposed in a number of endoscopic procedures. The aim of this double-blind, placebo-controlled study was to evaluate the efficacy of bilateral posterior quadratus lumborum block (pQLB) in alleviating pain and reducing postoperative opioid demand in patients following endoscopic extraperitoneal and laparoscopic prostatectomy. We enrolled 50 patients who were diagnosed with prostate cancer and scheduled for prostatectomy. They were randomized to receive preoperative, ultrasound-guided pQLB with the use of either 30 ml of 0.375 % ropivacaine (ropivacaine group) or 30 ml of 0.9 % NaCl (placebo group). Our primary endpoint was opioid consumption in the first 24 hours after surgery. Secondary endpoints were pain intensity at predefined timepoints and the incidence of nausea and vomiting and pruritus. No differences were detected between the ropivacaine and placebo groups in intravenous oxycodone consumption during the first 24 hours after surgery. Similarly, there were no differences in pain intensity at any of the timepoints assessed. The rate of nausea and vomiting was equal in both groups and pruritus was not observed. Application of bilateral pQLB does not reduce opioid consumption after minimally invasive prostatectomy.

Oxycodone 5 Miligram is More Effective Than Ketorolac 30 Miligram in Suppressing Cortisol Levels During General Anesthesia

Background: Preemptive analgesia is a developing clinical concept, which involves administering analgesics before pain stimulation occurs, to prevent the sensitization of the nervous system to further stimuli that can cause pain. Ketorolac has strong analgesic properties oxycodone is a semisynthetic opioid that is synthesized from the alkaloid thebaine opiate. Pain could induce stress hormone such as cortisol. Study to compare ketorolac and oxycodone with cortisol has not been investigated. This study aimed to assess intravenous administration of ketorolac 30 mg compared with intravenous 5 mg oxycodone for pain as measured by cortisol levels post-intervention in surgery performed under general anesthesia.&#x0D; Method: A study randomized controlled trial in double-blind form for patients at dr. Mohammad Hoesin Palembang, who will undergo elective surgery with general anesthesia at the Central Surgical Installation building, with the period September-October 2020. There are 24 study samples, to anticipate dropouts, an added sample size is 10%, so the sample size is 26 for each treatment group. The selection of subjects according to the purpose of the study was carried out by simple random. Data analysis using SPSS ver 22.0 software. Data were analyzed using Independent T-Test, Mann Whitney, and Chi-Square Test.&#x0D; Result: The results showed, there was a significant difference in the effectiveness of intravenous administration of ketorolac 30 mg and intravenous oxycodone 5 mg on pain as measured by cortisol levels in patients undergoing general anesthesia at dr. Mohammad Hoesin Palembang (p = 0.013). The value of cortisol levels in pre- operative patients who will be given general anesthesia at dr. There was no statistically significant difference between Mohammad Hoesin in the two groups (p = 0.107). The value of cortisol levels in preoperative patients who were given ketorolac 30 mg intravenously at dr. Mohammad Hoesin was 9.90 ± 4.2. The value of cortisol levels in postoperative patients who were given ketorolac 30 mg intravenously at dr. Mohammad Hoesin was 17.75 ± 6.08. The value of preoperative cortisol levels for patients who were given oxycodone 5 mg intravenously at dr. Mohammad Hoesin was 12.03 ± 5.10. The value of postoperative cortisol levels for patients who were given oxycodone 5 mg intravenously at dr. Mohammad Hoesin is 14.50 ± 4.75.&#x0D; Conclusion: There was a significant difference in the effectiveness of intravenous administration of ketorolac 30 mg and oxycodone 5 mg intravenously on BSS levels (p = 0.005) and VAS scores (p = 0.001) who underwent general anesthesia at dr. Mohammad Hoesin Palembang.

Orbitofrontal cortex and dorsal striatum functional connectivity predicts incubation of opioid craving after voluntary abstinence

We recently introduced a rat model of incubation of opioid craving after voluntary abstinence induced by negative consequences of drug seeking. Here, we used resting-state functional MRI to determine whether longitudinal functional connectivity changes in orbitofrontal cortex (OFC) circuits predict incubation of opioid craving after voluntary abstinence. We trained rats to self-administer for 14 d either intravenous oxycodone or palatable food. After 3 d, we introduced an electric barrier for 12 d that caused cessation of reward self-administration. We tested the rats for oxycodone or food seeking under extinction conditions immediately after self-administration training (early abstinence) and after electric barrier exposure (late abstinence). We imaged their brains before self-administration and during early and late abstinence. We analyzed changes in OFC functional connectivity induced by reward self-administration and electric barrier-induced abstinence. Oxycodone seeking was greater during late than early abstinence (incubation of oxycodone craving). Oxycodone self-administration experience increased OFC functional connectivity with dorsal striatum and related circuits that was positively correlated with incubated oxycodone seeking. In contrast, electric barrier-induced abstinence decreased OFC functional connectivity with dorsal striatum and related circuits that was negatively correlated with incubated oxycodone seeking. Food seeking was greater during early than late abstinence (abatement of food craving). Food self-administration experience and electric barrier-induced abstinence decreased or maintained functional connectivity in these circuits that were not correlated with abated food seeking. Opposing functional connectivity changes in OFC with dorsal striatum and related circuits induced by opioid self-administration versus voluntary abstinence predicted individual differences in incubation of opioid craving.

Impact of Bilateral Subcostal Plus Lateral Transversus Abdominis Plane Block on Quality of Recovery After Laparoscopic Cholecystectomy: A Randomized Placebo-Controlled Trial.

Previous research has not evaluated the potential effect of transversus abdominis plane (TAP) block on quality of recovery following laparoscopic cholecystectomy. Therefore, we investigated whether addition of the bilateral subcostal and lateral TAP (bilateral dual TAP [BD-TAP]) blocks to multimodal analgesia would improve the quality of recovery as assessed with the Quality of Recovery-40 (QoR-40). Patients age 18 to 60 years who were scheduled to undergo elective laparoscopic cholecystectomy were randomized to the BD-TAP or control group. The BD-TAP group received the BD-TAP block with multimodal analgesia under general anesthesia, using 0.25% ropivacaine, and the control group was treated with the same method, except that they received the sham block using 0.9% normal saline. Both groups had the same multimodal analgesia regimen, consisting of intravenous dexamethasone, propacetamol, ibuprofen, and oxycodone. The primary outcome was the QoR-40 score at 24 hours after surgery. Data were analyzed using the independent t test, Mann-Whitney U test, χ2 test, and Fisher exact test. Thirty-eight patients in each group were recruited. The mean QoR-40 score decreased by 13.6 (95% confidence interval [CI], 8.3-18.8) in the BD-TAP group and 15.6 (95% CI, 6.7-24.5) in the control group. The postoperative QoR-40 score at 24 hours after surgery did not differ between the 2 groups (BD-TAP group, median [interquartile range], 170.5 [152-178]; control group, 161 [148-175]; median difference, 3 [95% CI, -5 to 13]; P = .427). There were no differences between the 2 groups in the pain dimension of the QoR-40: 30.5 (95% CI, 27-33) in the BD-TAP group and 31 (95% CI, 26-32) in the control group; median difference was 0 (95% CI, -2 to 2); P = .77. Our results indicate that the BD-TAP block does not improve the quality of recovery or analgesic outcomes following laparoscopic cholecystectomy. Our results do not support the routine use of the BD-TAP block for this surgery.

Oxycodone target concentration dosing for acute pain in children.

Oxycodone pharmacokinetics have been described in premature neonates through to obese adults. Covariate influences have been accounted for using allometry (size) and maturation of oxycodone clearance with age. The target concentration is dependent on pain intensity that may differ over pain duration or between individuals. We assumed a target concentration of 35mcg.L-1 (acceptable range ±20%) to be associated with adequate analgesia without increased risk of adverse effects from respiratory depression. Pharmacokinetic simulation was used to estimate dose in neonates through to obese adults given intravenous or parenteral oxycodone. There were 84% of simulated oxycodone concentrations within the acceptable range during maintenance dosing. Variability around the simulated target concentration decreased with age. The maturation of oxycodone clearance is reflected in changes to context-sensitive halftime where clearance is immature in neonates compared with older children and adults. The intravenous loading and maintenance doses for a typical 5-year-old child are 100mcg.kg-1 and 33mcg.kg-1 .h-1 . In a typical adult, the loading dose is 100mcg.kg-1 and maintenance dose 23mcg.kg-1 .h-1 . Simulation was used to suggest loading and maintenance doses to attain an oxycodone concentration of 35mcg.L-1 predicted in adults. Although the covariates age and weight contribute 92% variability for clearance, there remains variability accounting for 16% of concentrations outside the target range. Duration of analgesic effect after ceasing infusion is anticipated to be longer in neonates where context-sensitive halftime is greater than older children and adults.