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A common opioid analgesic for cancer pain and, to a lesser extent, non-cancer pain, is hydromorphone (HM). Oral formulations as well as subcutaneous, intravenous, and other routes are frequently used for its administration. Its pharmacokinetics and pharmacodynamics have also been extensively researched. This article examines the pharmacological properties of hydromorphone and the development of its use both domestically and internationally with the goal of serving as a reference for the sensible clinical use of this medication.

The potential synergistic effects of combining cannabinoids and opioids for analgesia has received considerable attention. No studies to date have evaluated this combination in patients with chronic pain. The present study aimed to evaluate the combined analgesic and drug effects of oral opioid (hydromorphone) and delta-9-tetrahydrocannabinol (dronabinol), as well as their effects on physical and cognitive functioning, and human abuse potential (HAP) outcomes among individuals with knee osteoarthritis (KOA). This was a within-subject, double-blind, randomized, placebo-controlled study. Participants (N = 37; 65% women; mean age = 62) diagnosed with knee osteoarthritis of ≥3/10 average pain intensity were included. Participants received (1) placebo-placebo, (2) hydromorphone (4 mg)-placebo; (3) dronabinol (10 mg)-placebo, and (4) hydromorphone (4 mg)-dronabinol (10 mg). Clinical and experimentally-induced pain, physical and cognitive function, subjective drug effects, HAP, adverse events, and pharmacokinetics were evaluated. No significant analgesic effects were observed for clinical pain severity or physical functioning across all drug conditions. Little enhancement of hydromorphone analgesia by dronabinol was observed on evoked pain indices. While subjective drug effects and some HAP ratings were increased in the combined drug condition, these were not significantly increased over the dronabinol alone condition. No serious adverse events were reported; hydromorphone produced more mild adverse events than placebo, but hydromorphone + dronabinol produced more moderate adverse events than both placebo and hydromorphone alone. Only hydromorphone impaired cognitive performance. Consistent with laboratory studies on healthy adults, the present study shows minimal benefit of combining dronabinol (10 mg) and hydromorphone (4 mg) for analgesia and improving physical functioning in adults with KOA.

Purpose Although a single-injection interscalene block provides effective early postoperative analgesia following shoulder surgery, patients may experience “rebound pain” when the block resolves. Our objective was to determine if oral hydromorphone (2 mg) given six hours after a single-injection interscalene block for arthroscopic shoulder surgery leads to a clinically significant reduction in the severity of rebound pain. Methods After approval from research ethics boards, we conducted a two-centre, parallel-group, double-blind, randomized, placebo-controlled superiority trial. Patients received preoperative interscalene block, general anesthesia, and either hydromorphone or placebo six hours after the block. The primary outcome was the worst pain score in the first 24 hr postoperatively, measured on an 11-point (0–10) numerical rating scale. Results A total of 73 participants were randomly assigned to either the hydromorphone or placebo group. There was no statistically significant difference in the mean (standard deviation) worst pain score within 24 hr between the hydromorphone and placebo groups (6.5 [2.4] vs 5.9 [2.3]; mean difference, 0.6; 95% confidence interval, −0.5 to 1.8). Similarly, we did not find any significant difference in the pain trajectory, opioid use, or incidence of nausea and vomiting between the groups. The mean time to worst pain was 14.6 hr, and the mean time to first rescue analgesia was 11.3 hr after interscalene block. Conclusion Hydromorphone 2 mg given six hours after interscalene block did not reduce the severity of rebound pain postoperatively compared with placebo in patients undergoing arthroscopic shoulder surgery. Study registration ClinicalTrials.gov (NCT02939209); registered 19 October 2016.

In this 12-month randomized trial involving 251 long-term heroin users, injectable diacetylmorphine (the active ingredient in heroin) was more effective than oral methadone in achieving retention in treatment for addiction and in reducing illicit-drug use and other illegal activity. As compared with methadone, injectable diacetylmorphine was associated with more serious adverse events, including seizures and drug overdoses. In long-term heroin users, injectable diacetylmorphine (the active ingredient in heroin) was more effective than oral methadone in achieving retention in treatment for addiction and in reducing illicit-drug use and other illegal activity. Opioid dependence, most commonly manifested as heroin dependence, is a chronic relapsing condition 1 that is estimated to affect more than 1 million persons in North America. 2 , 3 The risks of opioid dependence include fatal overdoses, infections (including endocarditis, human immunodeficiency virus infection, and hepatitis C virus infection), social disintegration, violence, and crime. The associated burdens on communities include medical, public health, and criminal-justice costs as well as public disorder and crimes against property. Methadone, the standard opioid-substitution treatment, has been shown to reduce major risks associated with untreated opioid dependence in patients who are willing to undergo and are successfully . . .

Background Hydromorphone hydrochloride has a satisfactory postoperative analgesic effect for patients with colorectal cancer but is accompanied by a relatively high incidence of adverse events. Low-doses of naloxone combined with opioids for patient-controlled analgesia can reduce the incidence of drug-related adverse events. Nalmefene is a more selective opioid receptor antagonist than naloxone. The aim of this study was to determine the impact of low-doses of nalmefene on the analgesic effect and incidence of adverse events of patients with hydromorphone patient-controlled analgesia (PCA) undergoing colorectal radical surgery. Methods Ninety-nine patients undergoing elective laparoscopic or hand-assisted laparoscopic radical surgery under general anaesthesia were randomly divided into three groups. Group N1 received hydromorphone hydrochloride 0.15 mg/kg + nalmefene 2 µg/kg; Group N2 received hydromorphone hydrochloride 0.15 mg/kg + nalmefene 0.5 µg/kg; and the control group (Group C) received hydromorphone hydrochloride 0.15 mg/kg. All medications were diluted to 100 ml with normal saline. The primary outcome was pain intensity at 12 h after surgery; the secondary outcomes were the occurrence of nausea, vomiting and pruritus and the total analgesic consumption of the PCA pump at 1 h, 6 h, 12 h, 24 and 48 h after surgery. Results The NRS scores of Group N1 (2 µg/kg) were significantly lower than those of Group C (P = 0.025), and no difference was found between group N2 and group C (P > 0.05). Among the three groups, the NRS scores of Group N1 (2 µg/kg) were significantly lower than those of Group C at 12 h (P = 0.01) and 48 h (P = 0.01) postoperatively. Compared with 12 h postoperatively, the NRS scores were lower at 24 h postoperatively in Group N1 and Group C (P < 0.05) and significantly lower at 48 h postoperatively in all three groups (P < 0.001). There was a significant difference in the incidence of pruritus among the three groups (P = 0.036). Conclusions Nalmefene at a dosage of 2 µg/kg enhances the postoperative analgesic effect of hydromorphone hydrochloride and reduces the occurrence of postoperative pruritus. Trial Registration The trial was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR2000033520, date: 03/06/2020).

Background Radical surgery for colorectal cancer, associated with moderate to severe postoperative pain, needs multimodal analgesia with opioid for analgesia. Despite considerable advancements, the psychological implications and other side effects with opioid remain substantially unresolved. This study aimed to investigate the impact on mood, side effects relative to opioid, and recovery of the patients with hydromorphone or sufentanil intravenous patient-controlled analgesia (IV-PCA) in a multimodal perioperative analgesia regimen undergoing radical surgery for colorectal cancer. Methods Eighty patients undergoing elective laparoscopic or open radical surgery for colorectal cancer under general anesthesia were randomized to receive postoperative IV-PCA with either sufentanil (group S) or hydromorphone (group H). All patients received additionally flurbiprofen axetil 50 mg 30 min before the end of surgery and wound infiltration with 10 ml of 0.75% ropivacaine at the end of surgery. The primary endpoint was mood changes at 48 and 96 h after surgery. The secondary endpoints were the incidence of opioid-related adverse effects, recovery results and patient satisfaction after surgery. Results Seventy-two patients completed the study finally. There were no significant differences between the two groups with respect to preoperative parameters, surgical and anesthetic characteristics ( P  > 0.05). No obvious significant differences were observed in VAS score (at rest and during mobilization) and rescue analgesics use ( P  > 0.05). Compared with group S, the anger scores in the group H at 48 h and 96 h after surgery were significantly lower ( P  = 0.012 and 0.005; respectively), but the incidences of pruritus and nausea were higher ( P  = 0.028 and 0.008; respectively). There were no significant differences in the incidences of vomiting, respiratory depression, dizziness, Ramsay score, and hemodynamic changes between the two groups ( P  > 0.05). Moreover, there were no significant differences in the time to gastrointestinal recovery, time to drainage tube removal, time to walk, hospital stay after surgery and patient satisfaction between the two groups ( P  > 0.05). Conclusions Under the similar analgesia effect with different opoiods postoperatively, hydromorphone IV-PCA resulted in an improved mood, however, a higher occurrence of pruritus and nausea while compared to sufentanil IV-PCA in a multimodal perioperative analgesia regimen. Both regimens of opioid with IV-PCA may serve as promising candidates for good postoperative pain management, and provide with similar postoperative recovery for the patients undergoing radical surgery for colorectal cancer. Trial registration This study was registered with the Chinese Clinical Trial Registry on September 20, 2015 (URL: http://www.chictr.org.cn . Registry number: ChiCTR-IPR-15007112).

Postpartum pain significantly affects maternal recovery and overall health, underscoring the need for effective analgesic strategies. In this randomized controlled trial, 460 term parturients who underwent vaginal delivery were assigned to receive either a single epidural bolus of hydromorphone (HY group, n = 230) or an equivalent volume of normal saline (NS group, n = 230). Within 48 h postpartum, pain scores were significantly lower in the HY group than in the NS group ( p  < 0.001), with a greater proportion of women achieving pain scores ≤ 3 (76.47% vs. 27.93%; OR = 8.39, 97.5% CI 5.15–13.67). The HY group required fewer supplemental analgesics (6.79% vs. 24.77%; OR = 0.22, 97.5% CI 0.11–0.44), and the time to first rescue analgesia was prolonged (15.63 ± 5.98 vs. 12.01 ± 5.01 h). Although the incidence of adverse effects, including nausea, vomiting, dizziness, pruritus, and urinary retention, was greater in the HY group ( p  < 0.05), sleep disturbances were less common (5.43% vs. 30.18%; RR = 0.13). Furthermore, the HY Group exhibited superior maternal satisfaction ( p  < 0.001) and enhanced post-partum autonomy ( p  = 0.009), whereas no between-group differences in inflammatory markers were observed. Low-dose epidural hydromorphone provides effective postpartum pain management and represents a viable approach for acute postpartum analgesia, contingent on a favorable risk–benefit profile. Trial registration number : ChiCTR2200064687 (registration date: October 14, 2022; https://www.chictr.org.cn/ )

Buprenorphine is used to treat opioid use disorder (OUD). Weekly and monthly subcutaneous long-acting buprenorphine injections (CAM2038) provide more stable buprenorphine plasma levels and reduce the treatment burden, misuse, and diversion associated with sublingual transmucosal buprenorphine formulations. To characterize the pharmacokinetic/pharmacodynamic (PK/PD) relationship, a maximum inhibition (I max ) model was developed relating CAM2038 buprenorphine plasma concentration to drug liking maximum effect (E max ) visual analog scale (VAS; bipolar) score after intramuscular hydromorphone administration. Data included time-matched observations of buprenorphine plasma concentration and drug liking E max VAS score after hydromorphone 18 mg administration in 47 non-treatment-seeking adults with moderate to severe OUD in a phase 2 study. Analysis used non-‍linear mixed-effects modeling (NONMEM ® ). The final I max model adequately described the PK/PD relationship between buprenorphine plasma concentration and drug liking E max VAS score. Simulations showed drug liking was effectively blocked at low buprenorphine plasma concentrations (0.4 ng/mL) where the upper 95% confidence interval of the drug liking E max VAS score was below the pre-defined 11-point complete blockade threshold. The buprenorphine plasma concentration required to achieve 90% of the maximal effect (IC 90 ) of drug liking was 0.675 ng/mL. Interindividual variability in responses to buprenorphine was observed; some participants experienced fluctuating responses, and a few did not achieve drug liking blockade even with higher buprenorphine plasma concentrations. This affirms the need to individualize treatment and titrate doses for optimal treatment outcomes. PK/PD models were also developed for desire to use VAS and Clinical Opiate Withdrawal Scale (COWS) scores, with results aligned to those for drug liking.

In 2018, at least 4460 Canadians died from an opioid overdose, of which 94% were determined to be unintentional (accidental) overdoses. This represents a 9% increase in overdose deaths from 2017 and a 48% increase from 2016. The recent emergence of street fentanyl, carfentanil and other highly potent synthetic opioids increasingly cut into heroin and other street drugs is a pressing public health concern that has contributed substantially to the overdose emergency. Fentanyl and other synthetic analogs were implicated in 73% of opioid-related deaths in Canada in 2018, compared with 67% in 2017 and 50% in 2016. Individuals with severe opioid use disorder who inject opioids may not adequately benefit from oral opioid agonist treatment medications, for a variety of reasons. This guideline provides a framework for how to build a clinical practice of injectable opioid agonist treatment and recommends that this treatment should be considered for individuals with severe, treatment-refractory opioid use disorder and ongoing illicit injection opioid use.

Postoperative delirium (POD) significantly increases mortality and medical burden, however, evidence regarding the best opioid options after cardiac surgery remains limited.Using the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, we identified 8246 adult patients receiving > 70% of postoperative 24-h morphine milligram equivalents (MMEs) during the ICU length of stay as fentanyl, morphine, or hydromorphone. After 1:1:1 propensity score matching (PSM) ( n  = 701 per group), we compared POD incidence, mortality, length of stay, vasopressor- and ventilator-free days within 28 days.The matched cohort of 2103 patients showed balanced baseline characteristics (all SMD < 0.1). POD incidence was significantly lower in the morphine (10.6%) and hydromorphone (9.7%) groups than in the fentanyl group (22.1%). The hydromorphone group was associated with significantly lower rates of ICU (OR 0.07, 95% CI 0.01–0.53) and hospital mortality (OR 0.25,95% CI 0.08–0.74), as well as shorter ICU and hospital length of stay, and more vasopressor- and ventilator-free days within 28 days. Hydromorphone was associated with a significantly lower incidence of POD, lower mortality, shorter length of stay, and more vasopressor- and ventilator-free days within 28 days. Whereas morphine was also associated with a reduced risk of delirium and shorter length of stay, it was not significantly associated with a reduction in mortality.