Thermoresponsive Polymeric Hydromorphone Prodrug Provides Sustained Local Analgesia without Apparent Adverse Effects.

The extensive use of opioids for chronic pain management has contributed significantly to the current opioid epidemic. While many alternative nonopioid analgesics are available, opioids remain the most potent analgesics for moderate to severe pain management. In addition to the implementation of multimodal analgesia, there is a pressing need for the development of more effective and safer opioids. In this study, we developed a thermoresponsive N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based hydromorphone (HMP) prodrug (ProGel-HMP, HMP content = 16.2 wt %, in base form). The aqueous solution of ProGel-HMP was free-flowing at 4 °C but became a hydrogel when the temperature was raised to ≥37 °C, allowing sustained local retention when administered in vivo. When tested in the destabilization of the medial meniscus (DMM) mouse model of osteoarthritis (OA), ProGel-HMP was retained after intra-articular injection in the OA knee joint for at least 2 weeks postinjection, with low extra-articular distribution. ProGel-HMP was not detected in the central nervous system (CNS). A single dose of ProGel-HMP produced rapid and sustained joint pain resolution for greater than 14 days when compared to saline and dose-equivalent HMP controls, likely mediated through peripheral µ-opioid receptors in the knee joint. Systemic analgesia effect was absent in the DMM mice treated with ProGel-HMP, as evident in the lack of difference in tail flick response between the ProGel-HMP-treated mice and the controls (i.e., Healthy, Saline, and Sham). Repeated dosing of ProGel-HMP did not induce tolerance. Collectively, these data support the further development of ProGel-HMP as a potent, safe, long-acting and nonaddictive analgesic for better clinical pain management.

Polymorphisms in the A118G SNP of the OPRM1 gene produce different experiences of opioids: A human laboratory phenotype-genotype assessment.

Allelic variations in the A118G SNP of the OPRM1 gene change opioid signaling; however, evaluations of how allelic differences may influence opioid effects are lacking. This human laboratory paradigm examined whether the AA versus AG/GG genotypes determined opioid response profiles. Individuals with limited opioid exposure (N = 100) completed a five-day within-subject, double-blind, placebo-controlled, residential study. Participants were admitted (Day 1), received 4 mg hydromorphone (Day 2) and 0 mg, 2 mg and 8 mg hydromorphone in randomized order (Days 3-5) and completed self-reported visual analog scale (VAS) ratings and Likert scales, observed VAS, and physiological responses at baseline and for 6.5 h post-dose. Outcomes were analysed as peak/nadir effects over time as a function of genotype (available for N = 96 individuals; AG/GG = 13.5%, AA = 86.4%). Participants with AG/GG rated low and moderate doses of hydromorphone as significantly more positive (e.g., Good Effects VAS, coasting, drive, friendly, talkative, stimulation) with fewer negative effects (e.g., itchy skin, nausea, sleepiness), and were also observed as being more talkative and energetic relative to persons with AA. Persons with AG/GG were less physiologically reactive as determined by diastolic blood pressure and heart rate, but had more changes in core temperature compared with those with AA. Persons with AA also demonstrated more prototypic agonist effects across doses; persons with AG/GG showed limited response to 2 mg and 4 mg. Data suggest persons with AG/GG genotype experienced more pleasant and fewer unpleasant responses to hydromorphone relative to persons with AA. Future studies should replicate these laboratory findings in clinical populations to support a precision medicine approach to opioid prescribing.

Neuropsychiatric Effects Associated with Opioid-Based Management for Palliative Care Patients.

PURPOSE OF REVIEW: The abundance of opioids administered in the palliative care setting that was once considered a standard of care is at present necessitating that providers evaluate patients for unintentional and deleterious symptomology related to aberrant opioid use and addiction. Polypharmacy with opioids is dynamic in affecting patients neurologically, and increased amounts of prescriptions have had inimical effects, not only for the individual, but also for their families and healthcare providers. The purpose of this review is to widen the perspective of opioid consequences and bring awareness to the numerous neuropsychiatric effects associated with the most commonly prescribed opioids for patients receiving palliative care. RECENT FINDINGS: Numerous clinical and research studies have found evidence in support for increased incidence of opioid usage and abuse as well as undesirable neurological outcomes. The most common and concerning effects of opioid usage in this setting are delirium and problematic drug-related behavioral changes such as deceitful behavior towards family and physicians, anger outbursts, overtaking of medications, and early prescription refill requests. Other neuropsychiatric effects detailed by recent studies include drug-seeking behavior, tolerance, dependence, addictive disorder, anxiety, substance use disorder, emotional distress, continuation of opioids to avoid opioid withdrawal syndrome, depression, and suicidal ideation. Opioid usage has detrimental and confounding effects that have been overlooked for many years by palliative care providers and patients receiving palliative care. It is necessary, even lifesaving, to be cognizant of potential neuropsychiatric effects that opioids can have on an individual, especially for those under palliative care. By having an increased understanding and awareness of potential opioid neuropsychiatric effects, patient quality of life can be improved, healthcare system costs can be decreased, and patient outcomes can be met and exceeded.

Efficacy and safety of hydromorphone for cancer pain: a systematic review and meta-analysis.

BACKGROUND: Cancer pain significantly impacts individuals' quality of life, with opioids being employed as the primary means for pain relief. Nevertheless, concerns persist regarding the adverse reactions and effectiveness of opioids such as morphine. Hydromorphone, recognized as a potent opioid, is a viable alternative for managing cancer-related pain. The goal of this systematic review and meta-analysis was to determine the effectiveness and safety characteristics of hydromorphone in comparison to other opioids, as well as different methods of administering this medication within the scope of cancer pain treatment. METHODS: The PubMed, Embase, Cochrane Library, Scopus, and Web of Science databases were searched on December 25th, 2023. Following the PRISMA guidelines, a systematic investigation of databases was carried out, and suitable studies were chosen according to predetermined criteria (PICO framework). The meta-analyses were performed using a random-effects model. RESULTS: This review included 18 RCTs with 2271 patients who compared hydromorphone with morphine, oxycodone, or fentanyl, as well as other types of hydromorphone. Hydromorphone demonstrated efficacy similar to that of morphine and oxycodone in reducing cancer pain intensity, decreasing additional analgesic consumption, and improving quality of life. However, morphine showed slight superiority over hydromorphone in reducing breakthrough pain. Adverse events were comparable between hydromorphone and morphine or oxycodone. Patient-controlled and clinician-controlled hydromorphone administration routes yielded similar outcomes. CONCLUSIONS: The outcomes of this study substantiate the efficacy of hydromorphone in the management of cancer-related pain, demonstrating similar levels of effectiveness and safety as morphine and oxycodone. These findings are consistent with prior comprehensive analyses, suggesting that hydromorphone is a feasible choice for alleviating cancer-associated pain. Additional investigations are warranted to determine its efficacy in distinct patient cohorts and for different modes of administration. TRIAL REGISTRATION: Prospero registration ID: CRD42024517513. Link: https://www.crd.york.ac.uk/PROSPERO/#recordDetails .

The 50% effective dose of hydromorphone and morphine for epidural analgesia in the hemorrhoidectomy: a double-blind, sequential dose-finding study.

BACKGROUND: Although previous studies have showed that epidural morphine can be used as a complement to local anesthetics for analgesia after postcesarean delivery under spinal anesthesia, there is little known about the analgesic dosage of epidural morphine and hydromorphone for hemorrhoidectomy. Therefore, we conducted this study to examine the potency ratio of hydromorphone to epidural morphine as well as effective analgesic dose for 50% patients (ED50) undergoing elective hemorrhoidectomy. METHODS: 80 patients under elective hemorrhoidectomy with combined spinal and epidural anesthesia(CSEA) in department of anesthesia, Dongguan Tungwah hospital. To assess the ED50, patients were treated with epidural morphine or epidural hydromorphone randomly using a biased coin method-determined dose with a sequential allocation procedure. Following surgery, standardized multimodal analgesia was administered to all patients. A pain response score of ≤ 3 (on a scale of 0-10) was determined to be the effective dose after 24 h following CSEA. The ED50 in both groups were determined using the probit regression and isotonic regression method. We also measured pain intensity by patient interview using a 10 point verbal numeric rating scale prospectively at 6, 12 and 24 h after CSEA, and adverse effects were also noted. RESULTS: The ED50 was 0.350 mg (95% CI, 0.259-0.376 mg) in hydromorphone group and 1.129 mg (95% CI, 0.903-1.187 mg) in morphine group, respectively, estimated by isotonic regression method. Regression analysis with the probit, the ED50 of epidural hydromorphone was 0.366 mg (95% CI, 0.276-0.388 mg) and epidural morphine was 1.138 mg (95% CI, 0.910-1.201 mg). Exploratory findings showed that there was no difference between the most frequent dosages of epidural hydromorphone or epidural morphine in the occurrence of nausea, vomiting and pruritus. When administered with epidural opioids at ED50 doses or higher, 97.5% (39/40) of epidural morphine patients and 97.5% (39/40) epidural hydromorphone of patients were satisfied with their analgesia. CONCLUSION: Effective hemorrhoidectomy analgesia requires a 3:1 ratio of epidural morphine to epidural hydromorphone. Both drugs provide excellent patient satisfaction.

Different doses of nalmefene combined with hydromorphone hydrochloride for postoperative analgesia after colorectal surgery: a randomized controlled study.

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).

Frequency of Persistent Opioid Use 6 Months After Exposure to IV Opioids in the Emergency Department: A Prospective Cohort Study.

BACKGROUND: As rates of opioid use disorder in the general population have increased, some have questioned whether IV opioids should be used routinely for treatment of acute severe pain in the emergency department (ED). OBJECTIVES: We determined the incidence of persistent opioid use among opioid-naïve patients exposed to IV opioids in the ED. METHODS: This was a prospective observational cohort study conducted in two EDs in the Bronx, NY. Opioid-naïve adults with severe pain who received IV opioids in the ED were followed-up 6 months later by telephone interview and review of the state opioid prescription database. We defined persistent opioid use as filling 6 or more prescriptions for opioids in the 6 months following the ED visit or an average of one prescription per month. RESULTS: We screened 1555 patients. Of these, 506 patients met entry criteria and provided analyzable data. Morphine was the IV opioid most frequently administered in the ED (478, 94%), followed by hydromorphone (20, 4%). Of the 506, 8 (2%) received both IV morphine and hydromorphone and 63 (12%) participants were prescribed an opioid for use after the ED visit. One patient/506 (0%) met our apriori criteria for persistent opioid use within 6 months. CONCLUSION: Among 506 opioid naïve ED patients administered IV opioids for acute severe pain, only one used opioids persistently during the subsequent 6 months.

[Use of strongly acting sustained-release opioids in pediatrics : Pitfalls and solutions for morphine and hydromorphone]. / Anwendung stark wirksamer retardierter Opioide in der Pädiatrie : Fallstricke und Lösungen für Morphin und Hydromorphon.

BACKGROUND: In pediatrics, adequate treatment with potent opioids requires the administration of sustained-release preparations for many patients; however, the dosing and administration of sustained-release morphine and hydromorphone preparations via gastrointestinal tubes confronts providers with a major hurdle, especially as the company Mundipharma GmbH has discontinued the production and distribution of the preparation MST retard granules in 2019, which has been proven for these purposes in pediatrics. The aim of this study was to establish a production technique for available sustained-release opioid preparations, which are particularly suitable for use in the low-dose range required in pediatrics and which can also be administered via gastrointestinal tubes. METHOD: Low-dose preparations were produced by opening of morphine and hydromorphone capsules and weighing of the sustained-release pellets. To evaluate the partition, an analysis of the drug content via high performance liquid chromatography (HPLC) was conducted. Moreover, the administration via gastrointestinal tubes (charrière, Ch 8-Ch 10) was examined by an ex vivo experiment. RESULTS: The examination showed a practicable method to produce low dosages of sustained-release morphine and hydromorphone. The preparations are in accordance with the test for content uniformity of the European Pharmacopoeia (Ph. Eur.). Furthermore, the pellets were administered to gastrointestinal tubes Ch 8 (morphine) and Ch 10 (hydromorphone) by a syringe application technique and passed the tubes completely. CONCLUSION: The production technique can be considered as safe and enables the off-label oral application or application via gastrointestinal tubes of sustained-release opioids in pediatrics.

Pharmacokinetics of hydrorphone hydrochloride after intravenous and subcutaneous administration in ferrets (Mustela putorius furo).

OBJECTIVE: To determine the pharmacokinetic profile of hydromorphone 0.2 mg kg-1 administered by the intravenous (IV) and subcutaneous (SC) route in ferrets. STUDY DESIGN: Randomized, crossover study. ANIMALS: A group of eight adult ferrets weighting (mean ± standard deviation) 1.02 ± 0.22 kg. METHODS: Hydromorphone hydrochloride 0.2 mg kg-1 was administered IV or SC with a washout period of 7 days. Blood samples were collected from a jugular catheter before administration of hydromorphone and at 5, 10, 15, 20, 30, 45, 60, 90, 120, 240, 360, 480 and 720 minutes after hydromorphone administration. Plasma hydromorphone concentrations were determined by liquid chromatography/tandem mass spectrometry. Data were analyzed using a non-linear mixed effects model. RESULTS: The hydromorphone effective half-life was (t1/2) 45 min-1. Systemic clearance (Cls) and the volume of distribution (Vdss) following IV administration were 84.8 mL kg-1 min-1 and 5.59 L kg-1, respectively. The maximum observed plasma concentration was 59.53 ± 14.02 ng mL-1 within 10 minutes following SC administration. The SC bioavailability was 102.0%. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of IV and SC hydromorphone (0.2 mg kg-1) was characterized by a high clearance, short terminal half-life and large volume of distribution. Hydromorphone plasma concentrations remained greater than 2 ng mL-1 for 2 hours in most ferrets, a threshold reported to provide antinociceptive effects in other species. Hydromorphone was well absorbed following SC injection, providing an alternative administration route for clinical use in ferrets.

[Challenges in the treatment of opioid dependence]. / Aktuelle Herausforderungen in der Behandlung der Opioidabhängigkeit.

BACKGROUND: The number of persons using opioids has increased worldwide in the last decade, particularly the use of opioid analgesics in North America and Africa. In Germany, the prevalence of heroin addiction has remained relatively stable. METHOD: Narrative review of the literature. RESULTS: Opioid-assisted maintenance treatment (OMT) with the established substances methadone, levomethadone, slow-release morphine and buprenorphine is recommended as the first-line treatment for heroin dependence. The OMT reduces the use of heroin, mortality and individual suffering and improves the quality of life and physical health. A diamorphine and heroine-assisted treatment is an option for people who do not benefit from conventional OMT. An alternative to the use of diamorphine could be treatment with hydromorphone hydrochloride. The regulations on carrying out maintenance treatment in the Controlled Substances Prescription Act and the guidelines of the Federal Medical Association in Germany have been loosened based on the experiences of the COVID-19 pandemic, for example with respect to take-home prescriptions. There is an ongoing intensive discussion on how to deal with the decreasing number of outpatient clinics offering OMT. CONCLUSION: The first-line treatment for opioid addiction is opioid-assisted substitution treatment, including diamorphine and heroin-assisted treatment. Long-acting depot medications and implants still play a subordinate role.

Comparison of Analgesic Effects and Adverse Events of Hydromorphone PCIA Versus Sufentanil PCIA: A Retrospective Analysis.

PURPOSE: The aim of this study was to compare the analgesic effect and adverse events of hydromorphone patient-controlled intravenous analgesia (PCIA) without background dose versus sufentanil PCIA with background dose in patients after surgery. DESIGN: A retrospective analysis. METHODS: From June 2020 to May 2021, 1,594 eligible postoperative patients who received PCIA were included in this study. According to the types of opioids, patients were divided into two groups: the sufentanil group and the hydromorphone group. The Numerical Rating Scale, Functional Activity Scale, and Level of Sedation were used to evaluate the analgesic effects between the two groups. In addition, total patient-controlled analgesia (PCA) use, effective number of PCA compressions, and adverse effects of PCIA were compared between the two groups. FINDINGS: At 24 hours (h) after surgery, the Functional Activity Scale score in the sufentanil group was higher than that in the hydromorphone group (P < .05). Compared with the sufentanil group, total PCA use, total number of PCA compressions and effective number of PCA consumptions were significantly decreased in the hydromorphone group during a 48 hours period (P < .05). There were no statistical differences in Numerical Rating Scale score, Level of Sedation score, and adverse events between two groups at 24 hours and 48 hours after surgery. CONCLUSIONS: Compared with sufentanil PCIA with a background dose, under a similar analgesic effect, hydromorphone PCIA without a background dose provided lower PCA use. Our findings may provide useful evidence for more future studies related to postoperative analgesia.

Intraoperative hydromorphone decreases postoperative pain: an instrumental variable analysis.

BACKGROUND: Intraoperative administration of short-acting opioids might lead to increased postoperative pain and opioid requirements. There are few data describing the effects of intermediate-duration opioids such as hydromorphone on these outcomes. We have previously shown that a switch from a 2 mg to a 1 mg vial of hydromorphone was associated with decreased intraoperative dose administration. As presentation dose affected intraoperative hydromorphone administration and was unrelated to other policy changes, it could serve as an instrumental variable, assuming significant secular trends were not present during the study period. METHODS: In this observational cohort study of patients who received intraoperative hydromorphone (n=6750), an instrumental variable analysis was used to evaluate whether intraoperative hydromorphone administration affected postoperative pain scores and opioid administration. Before July 2017, hydromorphone was available as a 2-mg unit dose. From July 1, 2017 to November 20, 2017, hydromorphone was only available in a 1-mg unit dose. A two-stage least squares regression analysis was used to estimate causal effects. RESULTS: A 0.2-mg increase in intraoperative hydromorphone administration caused a decrease in admission PACU pain scores (mean difference, -0.8; 95% confidence interval, -1.2 to -0.4; P<0.001) and decreased maximum and time-weighted mean pain scores over 2 days postoperatively, without increased opioid administration. CONCLUSIONS: This study suggests that intraoperative administration of intermediate-duration opioids does not cause the same effects as short-acting opioids with respect to postoperative pain. Instrumental variables can be used to estimate causal effects using observation data when unmeasured confounding is present.

Clients' experiences on North America's first take-home injectable opioid agonist treatment (iOAT) program: a qualitative study.

BACKGROUND: To support public health measures during the COVID-19 pandemic, oral opioid agonist treatment (OAT) take-home doses were expanded in Western countries with positive results. Injectable OAT (iOAT) take-home doses were previously not an eligible option, and were made available for the first time in several sites to align with public health measures. Building upon these temporary risk-mitigating guidelines, a clinic in Vancouver, BC continued to offer two of a possible three daily doses of take-home injectable medications to eligible clients. The present study explores the processes through which take-home iOAT doses impacted clients' quality of life and continuity of care in real-life settings. METHODS: Three rounds of semi-structured qualitative interviews were conducted over a period of seventeen months beginning in July 2021 with eleven participants receiving iOAT take-home doses at a community clinic in Vancouver, British Columbia. Interviews followed a topic guide that evolved iteratively in response to emerging lines of inquiry. Interviews were recorded, transcribed, and then coded using NVivo 1.6 using an interpretive description approach. RESULTS: Participants reported that take-home doses granted them the freedom away from the clinic to have daily routines, form plans, and enjoy unstructured time. Participants appreciated the greater privacy, accessibility, and ability to engage in paid work. Furthermore, participants enjoyed greater autonomy to manage their medication and level of engagement with the clinic. These factors contributed to greater quality of life and continuity of care. Participants shared that their dose was too essential to divert and that they felt safe transporting and administering their medication off-site. In the future, all participants would like more accessible treatment such as access longer take-home prescriptions (e.g., one week), the ability to pick-up at different and convenient locations (e.g., community pharmacies), and a medication delivery service. CONCLUSIONS: Reducing the number of daily onsite injections from two or three to only one revealed the diversity of rich and nuanced needs that added flexibility and accessibility in iOAT can meet. Actions such as licencing diverse opioid medications/formulations, medication pick-up at community pharmacies, and a community of practice that supports clinical decisions are necessary to increase take-home iOAT accessibility.

Hydromorphone impurity 2,2-bishydromorphone does not exert mutagenic and clastogenic properties via in silico QSAR prediction and in vitro Ames and micronucleus test.

The opioid agonist hydromorphone is indicated for the management of severe acute and chronic pain given that alternate treatments are insufficient. While the genotoxicity profile of hydromorphone is well investigated, little is known about the genotoxic potential of its impurities. In this study, 2,2-bishydromorphone was tested in silico and in vitro for both its mutagenic potential in an Ames test performed with Salmonella typhimurium and Escherichia coli tester strains up to a maximum concentration of 5 mg per plate in the absence and presence of metabolic activation. Furthermore, it was tested for its ability to induce micronuclei in TK6 cells in a micronucleus test up to a maximum concentration of 500 µg/mL with or without an exogenous metabolic activation system. 2,2-Bishydromorphone did not reveal any potential for inducing mutagenicity or clastogenicity under the conditions of the respective tests and is therefore considered non-mutagenic and non-clastogenic/aneugenic in vitro. These results are in line with negative in silico quantitative structure-activity relationship (QSAR) prediction for 2,2-bishydromorphone mutagenicity and clastogenicity and provide evidence of good correlation of in silico and in vitro data. Conclusively, these studies add important new clinically relevant information on the safety of hydromorphone as the impurity of 2,2-bishydromorphone is proven to be non-mutagenic and non-clastogenic.

Controlled-release hydromorphone and risk of infection in adults: a systematic review.

BACKGROUND: Preliminary evidence suggests that people who inject drugs (PWID) may be at an increased risk of developing infective endocarditis (IE), hepatitis C virus (HCV) infection, and/or human immunodeficiency virus (HIV) infection from hydromorphone controlled-release formulation. The hypothesized mechanism is related to insolubility of the drug, which promotes reuse, leading to contamination of injecting equipment. However, this relationship has not been confirmed. We aimed to conduct a systematic review including adult PWID exposed to controlled-release hydromorphone and the risk of acquiring IE, HCV, and HIV. METHODS: We searched MEDLINE, EMBASE, and Evidence Based Medicine reviews from inception until September 2021. Following pilot testing, two reviewers conducted all screening of citations and full-text articles, as well as abstracted data, and appraised risk of bias using the Newcastle-Ottawa scale and Effective Practice and Organization of Care tool. Equity issues were examined using the PROGRESS-PLUS framework. Discrepancies were resolved consistently by a third reviewer. Meta-analysis was not feasible due to heterogeneity across the studies. RESULTS: After screening 3,231 citations from electronic databases, 722 citations from unpublished sources/reference scanning, and 626 full-text articles, five studies were included. Five were cohort studies, and one was a case-control study. The risk of bias varied across the studies. Two studies reported on gender, as well as other PROGRESS-PLUS criteria (race, housing, and employment). Three studies focused specifically on the controlled-release formulation of hydromorphone, whereas two studies focused on all formulations of hydromorphone. One retrospective cohort study found an association between controlled-release hydromorphone and IE, whereas a case-control study found no evidence of an association. One retrospective cohort study found an association between the number of hydromorphone controlled-release prescriptions and prevalence of HCV. None of the studies specifically reported on associations with HIV. DISCUSSION: Very few studies have examined the risk of IE, HCV, and HIV infection after exposure to controlled-release hydromorphone. Very low-quality and scant evidence suggests uncertainty around the risks of blood-borne infections, such as HCV and IE to PWID using this medication.

Coadministration of Curcumin and Hydromorphone Hydrochloride Alleviates Postoperative Pain in Rats.

This study aimed to explore the effect of curcumin and hydromorphone hydrochloride (HH) cotreatment on postoperative pain in rats. An incision + formaldehyde-induced pain rat model was established. Rats were treated with vehicle, curcumin, HH, or curcumin + HH. Paw mechanical withdrawal threshold and thermal withdrawal latency were measured at 1 d before surgery as well as 1 , 2 h, 1 , 3 , and 7 d after surgery to assess pain sensitivity. The L4-6 region of the spinal cord was collected from each rat at 2 h, 1 , 3 , and 7 d after surgery. Western blot analysis and immunohistochemical staining were carried out to detect the protein expression of pain-related genes. Quantitative real-time PCR and enzyme-linked immunosorbent assay were conducted to measure the expression and production of proinflammatory mediators. Compared with other groups, Curcumin + HH significantly reduced pain sensitivity in the model rats. Mechanistically, curcumin + HH suppressed protein expression of stromal cell-derived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), p-Akt, and c-fos while enhancing protein expression of nerve growth factor (NGF) in the dorsal root ganglia (DRG) of model rats. Curcumin + HH inhibited the expression and production of interleukin 1ß (IL-1ß), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), and p65 nuclear factor kappa B (NF-κB) in the DRG. Coadministration of curcumin and HH alleviates incision + formaldehyde-induced pain in rats, possibly by suppressing the SDF-1/CXCR4 pathway and the production of proinflammatory mediators. Our results provide curcumin and HH cotreatment as a promising therapeutic strategy in the management of postoperative pain.

Opioid and sedative requirements in extracorporeal membrane oxygenation patients on hydromorphone versus fentanyl.

BACKGROUND: The extracorporeal membrane oxygenation (ECMO) circuit causes pharmacokinetic alterations of medications which impact drug selection and dosing. Although hydromorphone has a favorable pharmacokinetic profile, it is unclear whether hydromorphone provides better patient-centered benefits compared to fentanyl. The objective of this study is to compare opioid and sedative requirements in ECMO patients started on a fentanyl- versus hydromorphone-based analgesia regimen. METHODS: This was a non-interventional retrospective cohort study. It was conducted at a single center in the cardiovascular intensive care units and cardiac intensive care units. We included venovenous (VV) or venoarterial ECMO patients. Patients who were started on a fentanyl continuous infusion within 24 h of cannulation were compared to patients started on a hydromorphone continuous infusion. RESULTS: A linear mixed effects model was performed to compare doses of opioid, sedative, and propofol between groups over time. We included 28 hydromorphone patients and 53 fentanyl patients, with 85% on VV ECMO. There were no differences between hydromorphone and fentanyl groups in opioid or sedative (including propofol and benzodiazepine) doses for any ECMO day (p value for interaction .63 and .83, respectively). Propofol doses alone, however, were significantly higher in the fentanyl group on ECMO days three, four, and five. CONCLUSIONS: There appear to be no major differences in opioid or sedative requirements whether ECMO patients are initiated on a hydromorphone- or fentanyl-based regimen.

Patient-Controlled Analgesia After Cardiac Surgery With Median Sternotomy: No Advantages of Hydromorphone When Compared to Morphine.

OBJECTIVES: To compare the efficacy, safety, and side effects of hydromorphone and morphine administered as patient-controlled analgesia (PCA) for postoperative pain therapy after cardiac surgery with median sternotomy. DESIGN: A retrospective analysis of data from 2 prospective, single-blinded, randomized trials. SETTING: A single-center intensive care unit at a university hospital. PARTICIPANTS: Forty-one adult patients undergoing cardiac surgery with median sternotomy. INTERVENTIONS: Postoperative pain therapy at the intensive care unit was performed by PCA with intravenously administered bolus doses of 0.2 mg of hydromorphone (n = 21) or 2 mg of morphine (n = 20). MEASUREMENTS AND MAIN RESULTS: Pain at rest and under deep inspiration regularly was assessed using the 11-point numerical rating scale (NRS). Blood pressure, heart rate, cardiac output, oxygen saturation, and respiratory rate were monitored, and adverse events were registered. The median (range) NRS rating at rest was 1.5 (0-5) after hydromorphone and 0.5 (0-5) after morphine, respectively (p = 0.41). The median NRS rating under deep inspiration was 3 (0-6) after hydromorphone and 4 (0-7) after morphine, respectively (p = 0.074). The dose ratio of morphine to hydromorphone during PCA was 5.7 (95% confidence interval: 2.9-7.6). Hemodynamics and respiration were stable and did not differ significantly. Postoperative nausea and vomiting were the most frequent adverse events, which were observed in 29% of the patients after hydromorphone and in 35% after morphine, respectively (p = 0.74). CONCLUSIONS: There were no significant differences in analgesic efficacy and safety between hydromorphone and morphine when used for postoperative pain therapy with PCA after cardiac surgery with median sternotomy.

Comparison of hydromorphone and butorphanol for management of pain in equine patients undergoing elective arthroscopy: a randomized clinical trial.

OBJECTIVE: To compare the effects of hydromorphone and butorphanol in horses undergoing arthroscopy and describe the pharmacokinetics of hydromorphone in anesthetized horses. STUDY DESIGN: Randomized controlled clinical trial. ANIMALS: A total of 40 adult horses admitted for elective arthroscopy. METHODS: Horses were randomly assigned to be administered intravenous hydromorphone (0.04 mg kg-1; group TxH; n = 19) or butorphanol (0.02 mg kg-1; group TxB; n = 21) prior to surgery as part of a standardized anesthetic protocol. Pain was scored by two observers unaware of group assignment using the Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) and a composite pain scale (CPS) prior to surgery (baseline), 2 hours (P2) and 4 hours (P4) following recovery from anesthesia. Blood samples were collected at various time points for determination of plasma hydromorphone concentration using liquid chromatography-tandem mass spectrometry. Data were analyzed with a mixed-effect model. RESULTS: Median (range) baseline EQUUS-FAP was 1.2 (0.0-4.0) with no effect of group, time points or interaction. Baseline CPS was similar between groups. Group TxH baseline CPS was 2.5 (0.0-10.0), increased at P2 [4.5 (0-10.0); p = 0.046] and returned to baseline values at P4 [3.0 (0.0-11.0)]. Group TxB baseline CPS was 2.0 (0.0-8.0), increased at P2 [3.5 (0.0-11.0); p = 0.009] and P4 [5.0 (0.0-11.0); p < 0.001]. Pharmacokinetic terminal half-life was 774 ± 82.3 minutes, area under the curve was 1362 ± 314 ng minutes mL-1, clearance was 30.7 ± 7.23 mL minute-1 kg-1 and volume of distribution at steady state was 884 ± 740 mL kg-1. CONCLUSIONS: Hydromorphone, but not butorphanol, decreased CPS back to baseline at P4 after recovery. CLINICAL RELEVANCE: Hydromorphone may provide superior postoperative analgesia compared with butorphanol in horses undergoing arthroscopy.

Application of Hydromorphone and Ropivacaine in Ultrasound-Guided Brachial Plexus Block of Children.

PURPOSE: This research was designed to investigate the effects of hydromorphone combined with ropivacaine anesthesia on brachial plexus block of upper limbs in children. DESIGN: This was a randomized prospective study. METHODS: A total of 120 children with upper limb fractures were included in this study and treated wtih open reduction and internal fixation (ORIF). The children were randomized into control group and research group. All of them were given a brachial plexus block and anesthetics (control group: 0.2% ropivacaine; research group: additional 5 µg/kg hydromorphone. FINDINGS: The time of onset and exercise recovery of the research group increased, and the use times of analgesic drugs decreased, which were significantly different from those of the control group (all P<.05). CONCLUSIONS: Hydromorphone can enhance the effectiveness of ropivacaine in blocking the brachial plexus and reduce postoperative pain and the demand for analgesics. Strong postoperative sedation can improve sleep quality and nursing satisfaction.