Oxycodone Group Research Articles

Preemptive Ketorolac is as Effective as Oxycodone Decreasing Plasma Cortisol Levels in Patients Undergoing Spinal Anesthesia

Introduction: Post-surgical pain is a complex problem, if not treated properly it can have multisystem negative effects. Hormone cortisol can be increased in stressful situations. A study on the effectiveness of ketorolac and another opioid on cortisol levels has been shown. However, a study about the effect of oxycodone on cortisol levels and its comparison with Ketorolac has never been done before. This study aimed to compare the effect of preemptive administration of 30 mg ketorolac and 5 mg oxycodone on plasma cortisol levels in patients undergoing spinal anesthesia.
 Methods: A double-blind randomized clinical trial was carried out between October and December 2020 in the central operating room of dr. Mohammad Hoesin Palembang. Surgical patients according to the inclusion criteria who received spinal anesthesia were randomly given 5 mg oxycodone and 30 mg ketorolac intravenously shortly after spinal anesthesia. Cortisol levels were measured before and after the intervention. Data analysis using SPSS ver. 20 Windows with a 95% confidence interval.
 Result: In total, 56 subjects were included. 29 samples in the ketorolac group and 27 samples in the oxycodone group. There were no significant differences in age, sex, nutritional status, blood sugar, and VAS score. There was no significant difference in the mean of cortisol levels before the intervention in the ketorolac group 12.9421 + 6.096 m/dL and the oxycodone group 14.033 + 4.315 m/dL (p = 0.446). The mean value of cortisol levels after intervention in the ketorolac group was 12.979 + 6.280 m/dL and oxycodone 15.353 + 11.704 m/dL, there was no significant difference in changes in cortisol before and after intervention in the Ketorolac group (p = 0.692) and Oxycodone (p = 0.552). The comparison level of cortisol changes between the two groups was not significantly different (p = 0.267).
 Conclusion: There was no difference in the comparison of the effect of preemptive administration of 30 mg IV ketorolac and 5 mg IV oxycodone on plasma cortisol levels in patients undergoing spinal anesthesia.

127 Impact of CYP2D6, CYP3A4, and CYP2C9 pharmacogenomic profile on pain relief and adverse events in Canadian children treated with oxycodone and ibuprofen

Abstract Primary Subject area Clinical Pharmacology and Toxicology Background Genomic variation impacts drug pharmacokinetics for commonly used children’s pain medications such as oxycodone and ibuprofen. In order to personalize and best treat children’s pain, how cytochrome enzyme polymorphisms for CYP2D6, CYP3A4, and CYP2C9 impact clinical effectiveness and safety for oxycodone and ibuprofen were studied. Objectives Primary objectives were to evaluate if allelic variations of CYP2D6, CYP2C9, and CYP3A4 would a) alter clinical effectiveness of ibuprofen and oxycodone for pain relief, and b) impact the occurrence of adverse events. Secondary objectives were to determine the degree to which these genetic and other clinical factors influence analgesic effectiveness and safety. Design/Methods This prospective, observational cohort included children aged 4-16 years who were seen in a pediatric emergency department (between June 2010 - July 2014) with an acute fracture and used ibuprofen OR oxycodone for at-home pain management. Saliva samples were obtained prior to discharge, and daily telephone follow-up collected self-reported pain scores, medication use, adverse events, and functional limitations for 3 days. Genotyping identified allelic variants of CYP2D6, CYP3A4, and CYP2C9. Pain was measured using the Faces Pain Scale-Revised. CYP2D6 metabolic phenotypes were determined based on identified variants. Regression analyses were employed to determine relationships between clinical and genomic patient characteristics, pain relief, and adverse events. Results We included 210 children (n=140 ibuprofen, n=70 oxycodone); mean age was 11.1 (±3.5) years, 66.2% were male, and 79.5% self-identified as Caucasian. The median pain reduction in the ibuprofen group was 4 (±2.0) and 4 (±3.5) in the oxycodone group on Day 1 (p = 0.69). Adverse events were experienced by 53.2% of the ibuprofen group and 78.3% of the oxycodone group (p < 0.001). CYP2D6 Intermediate Metabolizers had significantly less pain relief using oxycodone than Extensive Metabolizers (p = 0.04). CYP3A4 variants did not significantly impact pain relief or adverse events. Those with the decreased functioning CYP2C9*2 allele experienced less adverse events compared to the normal functioning allele CYP2C9*1 (p = 0.003) when using ibuprofen. Males (p = 0.035) and all children using non-pharmacological pain strategies (p = 0.02) experienced less pain relief with oxycodone. Conclusion A better understanding of pharmacogenomic variation could help personalize medication choice. Sex and non-pharmacologic pain management impact pain relief with oxycodone, warranting further study to better understand their relationship with opioid pain relief in children.

Efficacy of Different Preemptive Analgesia on Postoperative Analgesia, Oxidative Stress, and Inflammatory Response after Gynecological Laparoscopic Surgery.

Objective To observe and compare the analgesic effects of oxycodone, pentazocine, and ketorolac tromethamine pre-emptive analgesia on gynecological laparoscopic patients after operation and the effects on oxidative stress and inflammatory reaction. Methods A total of 64 patients who underwent elective gynecological laparoscopic surgery in Yiwu Central Hospital from June 2019 to December 2020 were randomly divided into four groups (n = 16). Before anesthesia induction, oxycodone (group A), pentazocine (group B), ketorolac tromethamine (group C), and normal saline (group D) were, respectively, administered. Patients' mean arterial pressure (MAP) and heart rate (HR) changes, visual analogue scale (VAS), Bruggemann comfort scale (BCS), serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), blood glucose (CLU), serum cortisol level, postoperative adverse reactions, and additional analgesia were recorded at each time point. Results The MAP levels of T2 (immediate intubation), T3 (immediate catheter removal), and T4 (5 min after catheter removal) in the four groups were higher than those of T1 (quiescent state), and the HR levels T2, T3, and T4 were lower than those of T1 (P < 0.05). The MAP and HR levels of T2, T3, and T4 in patients of groups A, B, and C were lower than those of group D in the same period (P < 0.05). The VAS and BCS scores of groups A, B, and C at 1, 6, 12, and 24 h after operation were better than those of group D at the same time, and the scores of group A at 1 h and 6 h after operation were better than those of groups B and C at the same time (P < 0.05). The levels of serum TNF-α, IL-6, and CRP in the four groups of patients at 6, 12, and 24 h after operation were higher than those before operation, but those in groups A, B, and C were lower than those in group D, and those in group A were higher than those in groups B and C at 12 h and 24 h after operation (P < 0.05). The CLU and serum cortisol levels in the four groups were significantly higher at 6, 12, and 24 h after operation, but those in groups A, B, and C were lower than those in group D, and those in group A were lower than those in groups B and C at 6 and 12 h after operation (P < 0.05). There was no significant difference in the incidence of adverse reactions within 24 h between the four groups (P > 0.05). The incidence of additional analgesia in groups A, B, and C was lower than that in group D (P < 0.05). Conclusion Oxycodone, pentazocine, and ketorolac tromethamine are effective and safe in inhibiting postoperative pain and the generation of inflammatory factors and relieving inflammatory state in gynecological laparoscopic pre-emptive analgesia. Oxycodone has better postoperative analgesic effect because it can effectively alleviate stress reaction.

Pain Control Following Photorefractive Keratectomy: A Prospective Clinical Trial Comparing Codeine Versus Oxycodone for the Management of Postoperative Pain.

To compare the efficacy of oral codeine plus acetaminophen versus oxycodone plus acetaminophen for severe pain control following photorefractive keratectomy (PRK). This single-center trial randomized 200 patients to receive codeine 30 mg/acetaminophen 325 mg (codeine group) or oxycodone 5 mg/acetaminophen 325 mg (oxycodone group)every 4 hours as needed for severe pain for 4 days following PRK. Patients recorded postoperative pain, tablet consumption, and tetracaine use. Patients were monitored at postoperative 1 day, 1 week, and 1, 3, and 6 months for visual acuity and follow-up. Study outcomes were mean postoperative pain, treatment and tetracaine use, and visual acuity. Analysis of 197 patients who completed the trial (97 codeine group and 100 oxycodone group) showed mean pain scores were lower in the codeine group throughout the intervention period. Mean pain scores were higher in the oxycodone group than the codeine group on postoperative days 2 and 4 (P = .017 and P = .034, respectively). The oxycodone group consumed more tablets than the codeine group, with a difference on postoperative day 2 (P = .019), and used a greater number of tetracaine drops (P = .015). Repeated measures analysis of variance showed significant improvement in visual acuity in both groups with no difference in visual outcomes (P = .81). Codeine/acetaminophen is as effective and safe as oxycodone/acetaminophen for pain control following PRK, with no clinical difference in overall pain control and long-term visual outcomes. This implies that treating postoperative pain after PRK with a Schedule III opioid (codeine) is effective and potentially decreases the risk of misuse by a higher regulated Schedule II opioid (oxycodone), lowering the potential for abuse and dependence. [J Refract Surg. 2021;37(9):582-589.].

The Effect of Oxycodone on Post-operative Pain and Inflammatory Cytokine Release in Elderly Patients Undergoing Laparoscopic Gastrectomy.

Background: To evaluate the effect of oxycodone on post-operative pain and inflammation in elderly patients undergoing laparoscopic gastrectomy.Methods: Sixty patients who were of both sexes, American Society of Anesthesiologists Physical Status (ASA-PS) Class I or II, over 65 years of age and undergoing an elective laparoscopic radical gastrectomy were randomly divided into two groups: an oxycodone group (Group O) including 20 males and 10 females and a sufentanil group (Group S) including 21 males and 9 females. The post-operative analgesia regimen was as follows: 40 mg of parecoxib sodium and 0.1 mg/kg of oxycodone was intravenously injected into Group O before the abdomen closure, while 40 mg of parecoxib sodium and 0.1 μg/kg of sufentanil was injected intravenously into Group S. Both groups were infiltrated with 20 ml of 1% ropivacaine at the end of the operation. The level of serum IL-6 and IL-10 were assayed immediately at the following timepoints: at the conclusion of surgery (T1), 1 h (T2), 6 h (T3), and 24 h (T4) after the completion of the surgery. The numerical rating scale (NRS), the Ramsay sedation score, analgesic-related adverse events, post-operative pulmonary inflammation events and the post-operative stay were recorded.Results: Compared with Group S, the serum IL-6 concentrations of Group O decreased at T3 and T4, while the serum IL-10 concentrations increased (P < 0.05). In Group O, the serum IL-6 concentrations at T3 and T4 were lower than those at T1 (P < 0.05). The incidence of post-operative nausea and vomiting (PONV) and pulmonary inflammation in Group O was lower than that in Group S (P < 0.05). At each time point, the NRS of visceral pain in Group O was lower than that in Group S. At 6 and 24 h after extubation, the NRS of incision pain in Group O was lower than that in Group S (P < 0.05).Conclusion: Oxycodone can regulate the level of inflammatory cytokines and reduce post-operative inflammatory response.

RETRACTED ARTICLE: Oxycodone versus morphine for analgesia after laparoscopic endometriosis resection

BackgroundThe objective of this study was to compare the analgesic potency of oxycodone versus morphine after laparoscopic deep infiltrating endometriosis resection.MethodsFifty patients undergoing laparoscopic deep infiltrating endometriosis resection were randomized to receive oxycodone or morphine intravenous-PCA after surgery. The primary outcome was opioid consumption during the 24 h after surgery. Secondary outcomes included time to first request for analgesia, the number of bolus, pain, sedation, nausea, vomiting, respiratory depression, and bradycardia. The prominent pain that caused patients to press the analgesic device was also recorded.ResultsOxycodone consumption (14.42 ± 2.83) was less than morphine consumption (20.14 ± 3.83). Compared with the morphine group, the total number of bolus (78 vs 123) was less and the average time to first request for analgesia (97.27 ± 59.79 vs 142.17 ± 51) was longer in the oxycodone group. The incidence of nausea was higher in the morphine group than in the oxycodone group at 0–2 h (45.45% vs 17.19%), 2–4 h (50% vs 17.19%),12–24 h (40.91% vs 13.04%) and 0–24 h (39.17% vs 19.13%). The overall incidence of vomiting was higher in the morphine group (27.27% vs 13.92%). There was no difference in visual analogue scale score, the incidence of respiratory depression, and bradycardia between groups. Of the three types of pain that prompted patients to request analgesia, the incidence of visceral pain was highest (59.9%, P < 0.01).ConclusionOxycodone was more potent than morphine for analgesia after laparoscopic endometriosis resection, and oxycodone has fewer side effects than morphine.Name of the registry: Chinese Clinical Trial RegistryTrial registration number: ChiCTR1900021870URL of trial registry record:http://www.chictr.org.cn/edit.aspx?pid=35799&htm=4Date of registration: 2019/3/13 0:00:00

Comparison of opioid prescribing upon hospital discharge in patients receiving tapentadol versus oxycodone following orthopaedic surgery.

Background The changing of opioids during the transition of care from hospital to home may be associated with harm. Objective To compare patients receiving tapentadol IR versus oxycodone IR following orthopaedic surgery during hospitalisation with regard to the changing of opioids at hospital discharge. Setting A major metropolitan tertiary referral hospital in Australia. Methods This is a retrospective cohort study. Participants included adult orthopaedic surgery patients receiving postoperative tapentadol IR or oxycodone IR during hospitalisation between 1 January 2018 and 30 June 2019. Main outcome measure The proportion of patients for whom the opioid prescribed was changed at hospital discharge. Results The study cohort included 199 patients. Of these, 100 patients received oxycodone and 99 patients received tapentadol post-operatively during hospitalisation. The mean age was 66years (SD, 12years) and 111 (56%) were female. The most common surgeries were total knee arthroplasty (91, 46%), total hip arthroplasty (63, 32%) and shoulder surgery (26, 13%). Patients in the tapentadol group were more likely to be changed to a different opioid upon hospital discharge than the oxycodone group (57% versus 9%, difference 48% [95% CI 36-59%, p < 0.01). After adjusting for confounders, post-operative tapentadol use was more likely to be associated with opioid changing upon discharge (OR 16.5, 95% CI 6.7 to 40.8, p < 0.01). Conclusions The post-operative use of tapentadol IR during hospitalisation was associated with an increased likelihood of opioid changing at hospital discharge. This practice could have patient safety implications.

Gastrointestinal Adverse Events in Hospitalized Patients Following Orthopedic Surgery: Tapentadol Immediate Release Versus Oxycodone Immediate Release

Tapentadol has relatively less effect on mu-opioid receptors compared with other opioids. This has the potential to reduce the occurrence of gastrointestinal (GI) adverse drug events (ADEs). To compare the GI ADEs during hospitalization between tapentadol immediate release (IR) and oxycodone IR following orthopedic surgeries. Retrospective cohort study. A major metropolitan tertiary referral hospital in Australia. Data for adult orthopedic surgery patients receiving postoperative tapentadol IR or oxycodone IR during hospitalization between January 1, 2018 and June 30, 2019, were collected from electronic medical records. The primary outcome was the occurrence of postoperative GI ADEs occurring during hospitalization. This was defined as a composite of nausea, vomiting, or constipation. The study cohort included 199 patients. Of these, 99 patients received tapentadol IR and 100 patients received oxycodone IR for postoperative pain during hospitalization. The mean age was 66 ± 12 years, and 111 patients (56%) were women. There was no significant difference between groups on the occurrence of GI ADEs (53% in oxycodone group and 51% in tapentadol group, difference 2%, 95% confidence interval [CI], -11% to 16%; P = 0.777). After adjusting for potential confounders, the use of tapentadol IR was not associated with a significant reduction of GI ADEs (odds ratio, 0.62; 95% CI, 0.32-1.20; P = 0.154). This was a single-center study and should be extrapolated with caution. As this was a retrospective study, the accuracy and availability of data were dependent on documentation in electronic medical records. Tapentadol IR is associated with similar GI ADE occurrence compared with oxycodone IR in patients with orthopedic postoperative pain during hospitalization.

Comparison of 2 mcg/kg of fentanyl and 150 mcg/kg oxycodone during induction on post-intubation hemodynamics: a randomized clinical trial

Context: Endotracheal intubation may cause increased blood pressure and heart rate. The use of fentanyl as pre-intubation medication blunts the hemodynamic changes. However, fentanyl has side effects of sedation and respiratory depression. Oxycodone is an opioid similar to fentanyl that can be used as pre-intubation medication with less effects on sedation and respiratory depression.&#x0D; Aims: This study compared the effect of 150 mcg/kg oxycodone and 2 mcg/kg fentanyl during induction on post-intubation blood pressure and heart rate changes.&#x0D; Methodology: The study was a double-blind, randomized clinical trial in 40 patients ASA I-II aged between 19 and 65-years old undergoing elective surgery under general anesthesia.&#x0D; The patients were divided into 2 groups, one receiving 150 mcg/kg oxycodone and one receiving 2 mcg/kg fentanyl during induction. Blood pressure and heart rate were recorded before induction (T0), before intubation (T1), just after intubation (T2), 3 min after intubation (T3) and 5 min after intubation (T4).&#x0D; Statistical data were analyzed using the unpaired t-test and Mann-Whitney test, where p &lt; 0.05 was considered significant.&#x0D; Results: The results showed significant differences (p &lt; 0.05) in MAP (and #61508;MAP) in every time point assessed (12.15 ± 6.753, 13.40 ± 6.143, and 17.59 ± 7.715 in the oxycodone group versus 3.65 ± 3.746, 6.05 ± 4.186, and 9.40 ± 6.484 in the fentanyl group, consecutively). This study also showed significant differences (p &lt; 0.05) in heart rate in every time point assessed (3,40 ± 4.212, 8.35 ± 4,891 and 10.45 ± 6.253 in the oxycodone group versus -4.80 ± 6.477, -2.15 ± 4.671, and -1.20 ± 6.978 in the fentanyl group, consecutively).&#x0D; Conclusions: Administration of 150 mcg/kg oxycodone during induction causes a smaller increase in post-endotracheal intubation blood pressure and heart rate compared to 2 mcg/kg fentanyl.&#x0D; Key words: Blood pressure; Fentanyl; Heart rate; Intubation; Oxycodone; Post-intubation hemodynamic&#x0D; Citation: Suwarman, Rismawan B, Rizky Heiry R. Comparison of 2 mcg/kg of fentanyl and 150 mcg/kg oxycodone during induction on post-intubation hemodynamics: a randomized clinical trial. Anaesth. pain intensive care 2021;25(2):138-142. DOI: 10.35975/apic.v25i2.1461&#x0D; Received: 25 September 2020, Reviewed: 4 January 2021, Accepted: 10 January 2021

Comparison of 2 µg/kg of fentanyl and 150 µg/kg oxycodone during induction on post-intubation hemodynamics: a randomized clinical trial

Context: Endotracheal intubation may cause increased blood pressure and heart rate. The use of fentanyl as pre-intubation medication may blunt the hemodynamic changes. However, fentanyl has side effects of sedation and respiratory depression. Oxycodone is an opioid similar to fentanyl that may be used as preintubation medication with less effects on sedation and respiratory depression.&#x0D; Aims: This study aimed to compare the effect of 150 µg/kg oxycodone and 2 µg/kg fentanyl during induction on post-intubation blood pressure and heart rate changes.&#x0D; Methodology: The study was a double-blind, randomized clinical trial in 40 patients ASA I-II aged between 19-65 years old undergoing elective surgery under general anesthesia.&#x0D; The patients were divided into 2 groups, one receiving 150 µg/kg oxycodone and one receiving 2 µg/kg fentanyl during induction. Blood pressure and heart rate were recorded before induction (T0), before intubation (T1), just after intubation (T2), 3 min after intubation (T3) and 5 min after intubation (T4).&#x0D; Statistical data was analyzed using unpaired t-test and Mann-Whitney test, where p &lt; 0.05 was considered significant.&#x0D; Results: The results showed significant differences (p &lt; 0.05) in MAP ( and #61508;MAP) in every time points assessed (12.15 ± 6.753, 13.40 ± 6.143, and 17.59 ± 7.715 in oxycodone group versus 3.65 ± 3.746, 6.05 ± 4.186, and 9.40 ± 6.484 in fentanyl group, consecutively). This study also showed significant differences (p &lt; 0.05) in heart rate in every time points assessed (3,40 ± 4.212, 8.35 ± 4,891 and 10.45 ± 6.253 in oxycodone group versus -4.80 ± 6.477, -2.15 ± 4.671, and -1.20 ± 6.978 in fentanyl group, consecutively).&#x0D; Conclusions: Administration of 150 µg/kg oxycodone during induction causes smaller increase in post-endotracheal intubation blood pressure and heart rate compared to 2 µg/kg fentanyl.&#x0D; Key words: Blood pressure; Fentanyl; Heart rate; Intubation; Oxycodone; Post-intubation hemodynamic&#x0D; Citation: Suwarman, Rismawan B, Rizky Heiry R. Comparison of 2 µg/kg of fentanyl and 150 µg/kg oxycodone during induction on post-intubation hemodynamics: a randomized clinical trial. Anaesth. pain intensive care 2021;25(1):71–75;&#x0D; DOI: 10.35975/apic.v25i1.1443&#x0D; Received: 25 September 2020, Reviewed: 4 January 2021, Accepted: 10 January 2021

Tapentadol versus oxycodone analgesia and side effects after laparoscopic hysterectomy: A randomised controlled trial.

Tapentadol is an opioid, which acts as a μ-opioid receptor agonist and inhibits noradrenaline reuptake in the central nervous system. This dual mechanism of action results in synergistic analgesic effects and potentially less side effects. This has been shown in treatment of chronic pain but postoperative studies are sparse. The main aim was to compare the analgesic effect of tapentadol with oxycodone after laparoscopic hysterectomy. Opioid side effects were recorded as secondary outcomes. Randomised, blinded trial. Single-centre, Oslo University Hospital, Norway, December 2017 to February 2019. Eighty-six opioid-naïve American Society of Anesthesiologists physical status 1 to 3 women undergoing laparoscopic hysterectomy for nonmalignant conditions. The patients received either oral tapentadol (group T) or oxycodone (group O) as part of multimodal pain treatment. Extended-release study medicine was administered 1 h preoperatively and after 12 h. Immediate-release study medicine was used as rescue analgesia. Pain scores, opioid consumption and opioid-induced side effects were evaluated during the first 24 h after surgery. The groups scored similarly for pain at rest using a numerical rating scale (NRS) 1 h postoperatively (group T 4.4, 95% CI, 3.8 to 5.0, group O 4.6, 95% CI, 3.8 to 5.3). No statistically significant differences were found between the groups for NRS at rest or while coughing during the 24-h follow-up period (P = 0.857 and P = 0.973). Mean dose of oral rescue medicine was similar for the groups (P = 0.914). Group T had significantly lower odds for nausea at 2 and 3 h postoperatively (P = 0.040, P = 0.020) and less need for antiemetics than group O. No differences were found for respiratory depression, vomiting, dizziness, pruritus, headache or sedation. We found tapentadol to be similar in analgesic efficacy to oxycodone during the first 24 h after hysterectomy, but with significantly less nausea. ClinicalTrials.gov, NCT03314792.

A 12-hour rapid titration method for cancer pain: a randomized, controlled, open-label study.

Opioid titration is the best way to achieve a balance of pain relief and tolerable side effects for moderate-to-severe cancer pain. Rapid dose titration helps to achieve early analgesia. We explored the efficacy and safety of a 12-hour rapid dose titration in treating cancer pain. Opioid-naïve patients with moderate-to-severe cancer pain were randomly divided into oxycodone group and morphine group. The medicines were adjusted to oxycodone sustained-release tablets after 12 hours, and the dose of oxycodone sustained-release tablets was adjusted every 12 hours. The analgesic efficacy and adverse reactions during the treatment were observed until the 72nd hour. A total of 106 patients were included in the analysis, with 51 patients in the oxycodone group and 55 in the morphine group. The pain control rate of all patients reached 96.2% 24 hours after treatment, and it was not significantly different between two groups (P=0.619). The proportion of Numeric Rating Scale (NRS) score that decreased by ≥50% was significantly higher in the oxycodone group than in the morphine group (P=0.013). In the first 12 hours and 24 hours, significantly lower proportions of patients in the oxycodone group experienced multiple episodes of breakthrough pain (BTP) than in the morphine group (P=0.032, P=0.021, respectively). The quality of life of the patients in the oxycodone group was significantly higher than that in the morphine group at the 24th hour (P=0.047), as was the degree to which the quality of life had improved (P<0.001). Only grade 1 or 2 adverse reactions were observed during the study period, and no significant difference between two groups. The 12-hour rapid dose titration method can achieve early analgesia, with mild adverse reactions. In particular, the rapid titration method with background sustained-release oxycodone can reduce BTP episodes and achieve significant early pain relief.

Analgesic Effects of Different κ-Receptor Agonists Used in Daytime Laparoscopic Cholecystectomy.

Background Comparing the effect of two different κ-receptor agonists, nalbuphine and oxycodone, and regular morphine in patients for prophylactic analgesia of acute pain after daytime laparoscopic cholecystectomy. Methods One hundred and twenty-four patients undergoing laparoscopic cholecystectomy were randomly allocated to receive nalbuphine (group N), oxycodone (group O), and morphine (group M). The three groups were all given intravenous injection (iv.) of 0.15 mg/kg injection before incision and 0.05 mg/kg injection at the end of pneumoperitoneum. The Visual Analogue Scale (VAS) scores (incision, visceral, and shoulder) and Ramsay sedation scores at 1, 2, 4, 8, 12, 16, 20, and 24 hours after surgery, the time of extubation, the incidence of postoperative adverse events, the satisfaction of pain treatment, and the duration of stay after surgery were all recorded. Results Compared with group M, the VAS scores of visceral pain at rest decreased in group N and group O at 1-8 h after surgery (P < 0.05). The VAS scores of visceral pain at movement in group N decreased longer than those in group O (P < 0.05). Compared with that of group M, the postoperative time in Ramsay sedation score of group O increased longer than that of group N (P < 0.05). Compared with group N, patients had worse sleep quality in group O, longer length of stay in group M, and lower satisfaction in both groups. Conclusion Compared with morphine, prophylactic use of the κ-receptor agonists, nalbuphine and oxycodone, during laparoscopic cholecystectomy can reduce postoperative visceral pain. Furthermore, the nalbuphine group had fewer adverse reactions, better analgesia, and better satisfaction.

How Successful Is Parenteral Oxycodone for Relieving Terminal Cancer Dyspnea Compared With Morphine? A Multicenter Prospective Observational Study

ContextParenteral morphine is widely used for dyspnea of imminently dying cancer patients (terminal dyspnea). However, the efficacy of other opioids such as oxycodone remains largely unknown. ObjectivesTo explore the efficacy of parenteral oxycodone vs. morphine by continuous infusion over 24 hours in cancer patients with terminal dyspnea. MethodsThis was a pre-planned subgroup analysis of a multicenter prospective observational study. Inclusion criteria were advanced cancer patients admitted to palliative care units, Eastern Cooperative Oncology Group performance status = 3-4, and a dyspnea intensity ≥2 on the Integrated Palliative care Outcome Scale (IPOS) for which oxycodone or morphine was initiated by continuous infusion. We measured dyspnea IPOS scores over 24 hours. ResultsWe analyzed 164 patients who received oxycodone (n = 26) and morphine (n = 138) for dyspnea (median survival = 5 days). The mean age was 70 years, 58 patients (35%) had lung cancer, and 97 (59%) had lung metastases. Complete case analysis revealed that mean dyspnea IPOS scores decreased from 3.0 (standard deviation = 0.7) to 1.5 (0.7) in the oxycodone group (difference in means = 1.5; P < 0.001), and from 2.9 (0.7) to 1.6 (1.0) in the morphine group (difference in means = 1.3; P < 0.001). No significant between-group differences existed in the IPOS scores at 24 hours (P = 0.753). Adverse events were seen in no and 5 patients in the oxycodone and morphine groups, respectively. ConclusionParenteral oxycodone may be equally effective and safe as morphine in the treatment of terminal dyspnea in cancer patients. Future randomized controlled trials should confirm the efficacy and safety of opioids other than morphine for terminal dyspnea.

Real-World Data on Nonmedical Use of Tramadol from Patients Evaluated for Substance Abuse Treatment in the NAVIPPRO Addiction Severity Index-Multimedia Version (ASI-MV®) Network.

IntroductionDrug safety studies regarding comparative risk of different opioid compounds are important as providers and regulatory agencies in the United States continue to balance pain management with an ongoing opioid epidemic.ObjectiveThe aim of this study was to evaluate nonmedical use (NMU) and diversion of tramadol and comparator opioids using real-world data from the Addiction Severity Index—Multimedia Version (ASI-MV®).MethodsA cross-sectional study design was used to evaluate past 30-day tramadol and comparator opioid NMU among adults assessed for substance abuse treatment using the ASI-MV from 2010 to 2018. Population and drug utilization-adjusted rates were studied, as well as patient characteristics, route of administration, and diversion.ResultsPast 30-day NMU of one or more prescription opioid was reported in 125,048 (22.6%) of ASI-MV assessments (2010–2018); 46.5% reported oxycodone, 43.2% hydrocodone, 8.1% morphine, and 7.2% tramadol. Male respondents ranged from 43.2% in the tramadol group to 51.8% in the oxycodone group. Majority (~ 76%) were Caucasian in all groups, with 86.9% Caucasian in the morphine group. Prevalence of past 30-day tramadol NMU was significantly lower than that of morphine, oxycodone, and hydrocodone for both population and utilization-adjusted rates. Rate of snorting of tramadol was 4–7 times lower than comparator opioids and injection was 14–34 times lower than morphine and oxycodone. Tramadol was most likely to be obtained via the patient’s own prescription while the comparator opioids were more often obtained via dealers or family/friends.ConclusionTramadol had a significantly lower rate of NMU than comparator opioids and was less likely to be diverted or used via higher-risk non-oral routes. These findings support previous evaluations by WHO and the United States Drug Enforcement Agency that concluded that tramadol has a low potential for abuse.

Opioid prescription for pain after osmotic dilator placement in abortion care: A randomized controlled trial

ObjectiveTo compare the overnight maximum pain scores after osmotic dilator placement prior to a dilation and evacuation (D&E) procedure in participants assigned to a prescription for ibuprofen alone or to ibuprofen plus oxycodone. Study designWe conducted a nonblinded pragmatic, randomized controlled trial to evaluate pain management among women undergoing osmotic dilator placement prior to D&E. We randomly assigned 70 participants at 12 weeks 6 days to 23 weeks 6 days gestation to receive a prescription for ibuprofen alone, or ibuprofen plus oxycodone. We assessed pain using a numeric rating scale (NRS; scale 0–10) at the following time points: Baseline, dilator placement, 2 and 6 hours, and preoperatively, where we also asked participants their maximum pain score. The primary outcome was mean individual NRS pain score change from baseline to maximum pain score. ResultsMaximum mean pain score (change from baseline) was 4.7 ± 2.9 in the ibuprofen group, and 6.5 ± 2.5 in the ibuprofen plus oxycodone group (p < 0.01). Participants in both groups reported highest NRS pain scores 2 hours after dilator placement, 3.9 ± 2.5 and 5.3 ± 2.6 respectively (p = 0.02). Average ibuprofen use in both arms was similar, and 81% of participants used at least 1 dose of ibuprofen after dilator placement. Of those randomized to prescription to ibuprofen plus oxycodone, only 51% used a dose of oxycodone. ConclusionsCompared to participants randomized to receive a prescription for ibuprofen, those randomized to receive a prescription for ibuprofen plus oxycodone reported higher maximum overnight pain scores. ImplicationsParticipants receiving a prescription for ibuprofen alone had lower maximum overnight pain scores following osmotic dilator placement. Given that opioid prescriptions did not appear to reduce overnight pain, minimizing these prescriptions would avoid opioid exposure for patients undergoing D&E.

Post-operative opioid-related adverse events with intravenous oxycodone compared to morphine: A randomized controlled trial.

The value of intravenous oxycodone compared to morphine remains controversial. The purpose of this trial was to compare opioid-related adverse events (ORAES) of intravenous oxycodone and morphine after total hip arthroplasty. Patients scheduled for total hip arthroplasty were enrolled in this study of post-operative pain treatment with intravenous oxycodone or intravenous morphine (ratio 1:1). After surgery, patients received similar drug regimens for titration in the post-operative care unit followed by intravenous patient-controlled analgesia (PCA). The primary outcome was the number of patients with ≥1 ORAEs within the first 24hours defined as either nausea, vomiting, respiratory depression, pruritus, urinary retention requiring evacuation, allergy, hallucinations. Secondary outcomes included pain scores and opioid consumption. The analysis included 238 patients with similar characteristics. There were 55 patients with at least one ORAEs in the oxycodone group vs 46 in the morphine group: 48% vs 40%, P=.19; relative risk=1.22 (0.91:1.63). Intravenous oxycodone vs intravenous morphine requirements were respectively (median, IQR): 6 (0-11) vs 8 (0-12) mg (P=.06) for titration, 15 (8-26) vs 8 (5-16) mg (P=.001) for PCA, and 22 (12-37) mg vs 19 (11-28) mg for cumulated intravenous consumption (P=.048). During the first 24hours, there was no difference in secondary outcomes (oxycodone vs morphine, respectively, in %): nausea (15 vs 13), vomiting (5 vs 5), urinary retention (20 vs 12) or pain scores. This study demonstrates that IV oxycodone did not significantly reduce ORAEs within the first 24hours compared to similar ratio of IV morphine.

Comparison of Analgesic and Adverse Effects of Oxycodone- and Fentanyl-Based Patient-Controlled Analgesia in Patients Undergoing Robot-Assisted Laparoscopic Gastrectomy Using a 55:1 Potency Ratio of Oxycodone to Fentanyl: A Retrospective Study.

PurposeOxycodone has affinities for both kappa- and mu-opioid receptors. Therefore, it has been used for postoperative analgesia of surgeries in which visceral pain is expected to be the main cause of pain. However, there are few studies of the 55:1 potency ratio of oxycodone to fentanyl when using it as intravenous patient-controlled analgesia (IV-PCA). Thus, we compared the analgesic and adverse effects of IV-PCA using the 55:1 potency ratio of oxycodone to fentanyl in patients who underwent robot-assisted laparoscopic gastrectomy.Patients and MethodsThis retrospective study included 100 patients using an automatic PCA pump with oxycodone or fentanyl who underwent robot-assisted laparoscopic gastrectomy between January and November 2017. All patients were provided with an IV-PCA consisting of 20 μg/kg of fentanyl or 1.1 mg/kg of oxycodone mixed with 0.9% normal saline solution to a total volume of 250 mL, which was infused basally at a rate of 0.1 mL/h with a bolus dose of 1 mL and lockout time of 6 min. The primary and secondary endpoints were to evaluate the efficacies of IV-PCA using the 55:1 potency ratio of oxycodone to fentanyl on analgesic and adverse effects.ResultsPain intensity on arrival at the post-anesthesia care unit (PACU; 3.6±1.4 vs 4.4±2.0, P=0.031) and additional analgesic requirement within an hour after surgery (including the PACU period) (12% vs 37%; P=0.005) were significantly lower in the oxycodone group (n=49) than in the fentanyl group (n=51). Regarding adverse effects, the rate of postoperative nausea within 1 h after surgery (2% vs 16%; P=0.031) was also significantly lower in the oxycodone group than that in the fentanyl group.ConclusionOxycodone-based IV-PCA by dose calculations with a 55:1 potency ratio may achieve better analgesia without any significant adverse effects, when using IV-PCA in patients undergoing robot-assisted laparoscopic gastrectomy.

Oxycodone inhibits myocardial cell apoptosis after myocardial ischemia-reperfusion injury in rats via RhoA/ROCK1 signaling pathway.

The purpose of this study was to investigate the effect of oxycodone on myocardial ischemia-reperfusion injury in rats through the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) signaling pathway. A total of 48 Sprague-Dawley (SD) rats were randomly divided into sham operation group, model group, oxycodone group, and inhibitor group, with 12 rats in each group. The rats in the sham operation group only underwent thoracotomy without ischemia-reperfusion injury, those in the model group were used to prepare the myocardial ischemia-reperfusion model with normal saline intervention, those in the oxycodone group were used to prepare the myocardial ischemia-reperfusion model with oxycodone intervention, and those in the inhibitor group were utilized to prepare the myocardial ischemia-reperfusion model with AG490 intervention. Then, the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (BAX) were detected by immunohistochemistry, the relative protein expressions of RhoA and ROCK1 were examined via Western blotting, and the messenger ribonucleic acid (mRNA) expressions of Bcl-2 and BAX were measured by quantitative Polymerase Chain Reaction (qPCR). Thereafter, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was adopted for apoptosis detection, and the levels of creatine kinase-muscle/brain (CK-MB), and cardiac Troponin I (cTnI) in serum were detected using an automatic biochemical analyzer. Immunohistochemistry results showed that compared with those in the sham operation group, the positive expression of BAX was remarkably increased (p<0.05), while that of Bcl-2 was significantly decreased (p<0.05) in the model group, oxycodone group, and inhibitor group. Compared with the model group, oxycodone group and inhibitor group had an evidently reduced positive expression of BAX (p<0.05) and an evidently raised positive expression of Bcl-2 (p<0.05). No differences were found in the positive expressions of BAX and Bcl-2 between oxycodone group and inhibitor group (p>0.05). According to Western blotting results, the relative protein expressions of RhoA and ROCK1 in the model group, oxycodone group, and inhibitor group were notably increased compared with those in the sham operation group (p<0.05). In comparison with those in the model group, the relative protein expressions of RhoA and ROCK1 in the oxycodone group and inhibitor group were predominantly reduced (p<0.05). There were no differences in the relative protein expressions of RhoA and ROCK1 between oxycodone group and inhibitor group (p>0.05). Moreover, it was discovered from qRT-PCR results that compared with those in the sham operation group, the mRNA expression of BAX was markedly raised (p<0.05), whereas that of Bcl-2 was decreased predominantly (p<0.05) in the model group, oxycodone group, and inhibitor group. Compared with the model group, oxycodone group, and inhibitor group had an evidently reduced mRNA expression of BAX (p<0.05) and a significantly raised mRNA expression of Bcl-2 (p<0.05). No differences were found in the mRNA expressions of BAX and Bcl-2 between oxycodone group and inhibitor group (p>0.05). In addition, TUNEL assay results manifested that compared with sham operation group, model group, oxycodone group, and inhibitor group had a markedly elevated apoptosis rate (p<0.05). In comparison with the model group, the apoptosis rate in oxycodone group and inhibitor group was remarkably reduced (p<0.05). There was no difference in the apoptosis rate between oxycodone group and inhibitor group (p>0.05). According to biochemical analysis results, the serum levels of CK-MB and cTnI in model group, oxycodone group, and inhibitor group were significantly increased compared with those in the sham operation group, with statistically significant differences (p<0.05). The levels of serum CK-MB and cTnI in the oxycodone group and inhibitor group were substantially lowered in comparison with those in the model group, displaying statistically significant differences (p<0.05). Besides, the levels of serum CK-MB and cTnI in the oxycodone group were not different from those in the inhibitor group (p>0.05). Oxycodone inhibits myocardial cell apoptosis after myocardial ischemia-reperfusion injury by suppressing the RhoA/ROCK1 signaling pathway.

Narcotic Use After Cesarean: Separate Versus Combined Regimens of Oxycodone and Acetaminophen [22E

INTRODUCTION: In the management of post-cesarean analgesia narcotic medications remain a mainstay of treatment. It is well documented that NSAIDS and acetaminophen help reduce the amount of narcotic needed to control post-operative pain, however there is still no consensus on which multimodal regimen is superior. In our study we investigate the impact of different analgesic regimens on narcotic use during post-cesarean hospitalization. METHODS: This study is a part of a larger IRB approved study examining the impact of an Enhanced Recovery After Surgery (ERAS) protocol for cesarean deliveries. Data collected from 2/1/19–5/31/19 were part of the retrospective chart review of patients who underwent cesarean section. The study was powered to detect a 30% reduction in narcotic use between groups with of 86 per group. Statistical analysis was completed using SAS. RESULTS: The primary outcome was intravenous morphine mg equivalents (mEq) per 12-hour period while hospitalized. Analysis was performed on two dosing regimens: oxycodone (ordered separately from acetaminophen) (N=67), and combined oxycodone-acetaminophen (N=83). Ninety-five percent of patients additionally received NSAIDS in the form of ketorolac and/or ibuprofen. After controlling for potential confounders, patients in the oxycodone group received an average of 4.6 mEq/12 hours compared to the combination oxycodone-acetaminophen group who averaged 5.7 mEq/12 hours, P=.01. Over an average length of stay of 80.8 hours this equaled a difference of 7.41 mEq or 14.82 mg oxycodone, a 19.3% reduction. CONCLUSION: Our findings suggest that for patients undergoing cesarean section a regimen of oxycodone and acetaminophen ordered separately may lead to a clinically significant decrease in narcotic use during admission.