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To determine the pharmacokinetic profile of hydromorphone 0.2 mg kg–1 administered by the intravenous (IV) and subcutaneous (SC) route in ferrets. Randomized, crossover study. A group of eight adult ferrets weighting (mean ± standard deviation) 1.02 ± 0.22 kg. 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. The hydromorphone effective half-life was (t 1/2) 45 min–1. Systemic clearance (Cl s) and the volume of distribution (Vd ss) 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%. 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. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to compare the efficacy of midazolam/meperidine (M/M) vs midazolam/hydromorphone (M/H) for enteral moderate sedation along with inhalational sedation in pediatric dental patients. Methods: This retrospective chart review analyzed the charts of pediatric patients who received dental treatment under enteral moderate sedation with either M/M or M/H in combination with inhalational sedation (nitrous oxide/oxygen) at El Rio Community Health Centers (affiliated with NYU Langone) in Tucson, Arizona, from July 2014 to December 2020. Included subjects were between 2 and 5 years of age, less than 20 kg, and otherwise healthy. In addition to demographic and drug-dosing data, treatment completion, sedation level, behavioral score, overall effectiveness, and sedation duration data were collected and analyzed from each patient's chart. Results: No statistically significant differences were observed when comparing the 2 drug regimens in treatment completion (P =.89), sedation level (P =.74), and overall effectiveness (P =.70). There was a statistically significant difference in behavior scoring, with the M/H group demonstrating higher scores (P =.04) than the M/M group. Conclusion: The combination of midazolam and hydromorphone may provide an effective alternative to midazolam and meperidine when used with inhalational sedation (nitrous oxide/oxygen) for the moderate sedation of pediatric dental patients. [ABSTRACT FROM AUTHOR]

Context: Equianalgesic tools are commonly utilized to guide dose of analgesic therapy, but there is no national consensus on equianalgesic calculations in the United States. Objectives: To propose a summary of current opioid equianalgesic data that include variations and trends among national institutions. Methods: Opioid equianalgesic tools were obtained between May and September 2021. For meperidine, tramadol, codeine, hydrocodone, morphine, oxycodone, oxymorphone, hydromorphone, levorphanol, fentanyl, and tapentadol, details of adjustment for incomplete tolerance, opioid equianalgesic ratios, and formulation types were collected and analyzed. Baseline opioid pharmaco kinetic data were obtained through manufacturer labels on FDA databases, including half-life (T1/2), volume of distribution (Vd), clearance (Cl), area under the curve (AUC), max concentration (Cmax), and time to max concentration (Tmax). Results: Thirty-two institutions equianalgesic tools were included with each study opioid appearing on an average of 23 institutions tools. Few tools contained guidance on levorphanol or tapentadol; or included minimum and maximum recommended doses. All tools included guidance on fentanyl, hydromorphone, oxycodone, morphine, and hydrocodone. A minority of tools included guidance on cross-tolerance considerations (n = 12, 37.5%). Oral-tramadol-to-oral-morphine and oral-hydromorphone-to-intravenous (IV)-hydromorphone had the largest variances across equianalgesic tools (6.7 ± 2.8 and 4.06 ± 1.2 mg, respectively). Conclusion: Opioid equianalgesia tools from across the United States demonstrated significant variation in their inclusion of guidance on adjustment for incomplete cross-tolerance, oral-to-IV, and oral-to-oral opioid equianalgesic ratios, and which opioids and formulations were listed. Tramadol and hydromorphone had the most variation in their equianalgesic guidance among the opioids.

Abstract 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.

Liang B, Li C, Zhou Z, Xie Y. Drug Des Devel Ther. 2023;17:1037–1045. We, the Editor and Publisher of the journal Drug Design, Development and Therapy have retracted the published article. Following publication of the article, concerns were raised about the duplication of images from Figure 4. Specifically, Images for Figure 4A, Migration, 0 and 200; 400 and 800; and Invasion, 0 and 400 have been duplicated. The corresponding author did not respond to our queries and was unable to provide a satisfactory explanation for how the images came to be duplicated or provide satisfactory original data for the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Purpose Opioid conversion calculators (OCCs) are used to convert between opioids. The purpose of this study was to describe the variability in OCC results in critically ill children transitioned from fentanyl to hydromorphone infusions. Methods This was a descriptive, retrospective study. Seventeen OCCs were identified and grouped into 6 groups (groups 1-6) based on the equianalgesic conversions. The OCCs were used to calculate the hydromorphone rate in critically ill children (<18 years) converted from fentanyl to hydromorphone. Information from a previous study on children stabilized on hydromorphone (defined as the first 24-hour period with no change in the hydromorphone rates, <3 hydromorphone boluses administered, and 80% of State Behavior Scale scores between 0 and –1) were utilized. The primary objective was to compare the median hydromorphone rates calculated using the 17 OCCs. The secondary objective was to compare the percent variability of the OCC-calculated hydromorphone rates to the stabilization rate. Results Seventeen OCCs were applied to data on 28 children with a median age and hydromorphone rate of 2.4 years and 0.08 mg/kg/h, respectively. The median hydromorphone rate calculated using the 17 OCCs ranged from 0.06 to 0.12 mg/kg/h. Group 3 and group 6 OCCs resulted in a calculated hydromorphone rate that was higher than the stabilization rate in 96% and 75% of patients, respectively. Use of group 4 and group 5 OCCs resulted in a calculated hydromorphone rate that was lower than the stabilization rate in 64% and 75% of patients, respectively. Conclusion Given the considerable variability of OCCs, caution should be used when applying OCCs to critically ill children. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hydromorphone and morphine are the common drugs used for the treatment of moderate to severe cancer pain. Patient controlled subcutaneous analgesia (PCSA) is an effective technique to manage cancer pain. However, few studies have been conducted to show the efficacy and safety of PCSA of hydromorphone for the relief of cancer pain. To explore the short-term efficacy and safety of PCSA elicited by hydromorphone for moderate to severe cancer pain. This was a single-center, randomized, active-controlled, double-blind trial (from April 2019 to August 2021). Sixty patients with moderate to severe cancer pain were randomized (1:1) to hydromorphone or morphine groups according to drug delivery by PCSA. The primary outcome was the pain intensity measured by a numerical rating scale (NRS) at 72 hours. Secondary outcomes included pain intensity measured by NRS at baseline, 15 minutes, 30 minutes, two hours, eight hours, 24 hours and 48 hours. The daily occurrence of breakthrough pain (BTP), impact of pain on quality of life measured by the brief pain inventory (BPI), the daily additional consumption of opioids and the incidence of adverse events were also recorded. Adverse events included nausea, vomiting, dizziness, constipation and respiratory depression. A total of 57 patients (28 patients in the hydromorphone group and 29 patients in the morphine group) in the West China Hospital of Sichuan University were investigated. The mean (standard deviation [SD]) NRS in the two groups at baseline was 7.8 (1.7) in the hydromorphone group and 7.6 (1.7) in the morphine group, and at 72 hours were 3.4 (1.8) and 3.2 (1.5), respectively. The postoperative NRS in both groups was decreased significantly compared to baseline. The mean (SD) NRS at 30 minutes in the hydromorphone group was significantly lower than in the morphine group (3.9 [2.6] vs. 5.3 [2.1], P = 0.035). The daily occurrence of BTP in both groups at 48 hours and 72 hours decreased significantly compared to the corresponding baseline (P < 0.05), and there was no significant difference between the two groups. The total scores and sub-item scores of BPI at 24 hours and 72 hours after PCSA in both groups decreased significantly from baseline. A comparison of daily additional consumption of opioids between the two groups revealed no statistically significant difference. There were no significant differences in the incidences of nausea, vomiting, dizziness or constipation between the two groups (P > 0.05). This study found that the PCSA of both hydromorphone and morphine could effectively and safely relieve short-term moderate to severe cancer pain. Of note, the PCSA of hydromorphone took effect more quickly than that of morphine. [ABSTRACT FROM AUTHOR]

Kratom is a plant originating in Southeast Asia that has been used for its dose‐dependent stimulant and opioid effects. The main active compound in kratom is mitragynine, an alkaloid with affinity for the mu‐opioid receptor. Toxicity and fatalities related to kratom use have increased substantially in recent years. In this case report, we describe a 44‐year‐old man who was found deceased in bed. The only significant finding at autopsy was abdominal distension with >4 L of ascites. Toxicology testing was performed on femoral blood which showed 79 ng/mL of hydromorphone, 560 ng/mL of mitragynine, and 240 ng/mL of olanzapine. In addition, creatinine and urea in vitreous humor were significantly elevated, consistent with renal impairment. Death was attributed to hydromorphone toxicity with mitragynine being a contributing factor. [ABSTRACT FROM AUTHOR]

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This retrospective cohort study aimed to compare post-surgical opioid consumption before and after a PCA (patient-controlled analgesia) shortage. The study evaluated patients who received PCA vs. nurse-administered opioid analgesia (non-PCA). Two hundred and twenty-four patients =18 years who were initiated on analgesia within 24 h of surgery were included. The primary outcome was opioid consumption in average daily oral morphine milliequivalents (MME). The results showed that patients in the PCA group had increased MME consumption (162 ± 100.4 vs. 70.7 ± 52.8, p < 0.01), increased length of hospital stay (4.2 vs. 3.2 days, p < 0.01), and increased frequency of nausea (33 vs. 17.9%, p < 0.01). After controlling for confounding factors, the PCA group utilized significantly more opioids (84.6 MME/day, p < 0.01) than the non-PCA group. There was no difference in pain AUC/T (0.19 ± 0.07 vs. 0.21 ± 0.08, p = 0.07) and average opioid prescribing upon discharge (150 [77.5-360] vs. 90 [77.5-400], p = 0.64) between the PCA group and non-PCA group, respectively. These results question the routine use of PCA in post-operative patients due to the increased risk of opioid consumption, longer length of hospital stay, and higher incidence of nausea. [ABSTRACT FROM AUTHOR]

IntroductionDosing recommendations for hydromorphone intravenous constant rate infusion (IV CRI) are derived from simulations following IV bolus administration. While this extrapolated dose regimen has been described clinically, pharmacokinetics (PK) of hydromorphone infusions in dogs are not yet described. The study objective was to describe the PK of hydromorphone in healthy dogs receiving an IV bolus followed by an IV CRI for 48 h.MethodsA prospective, experimental study was performed involving the administration of hydromorphone (0.1 mg/kg IV bolus then IV CRI 0.01 mg/kg/h over a 48 h period) to 6 healthy Beagle dogs. Blood samples were collected at 16 time points between 0 and 58 h relative to the initial bolus. Plasma hydromorphone concentrations were analyzed by high pressure liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameter estimates were obtained with compartmental methods using commercially available software.ResultsA two-compartment model with first order elimination was used. At the end of the infusion, median (range) plasma hydromorphone concentrations were 6.8 (5.5–19.6) ng/mL. The median total body clearance was 30.4 (19.8–36.7) mL/min/kg; volume of distribution at steady state was 4.5 (3.2–7.8) L/kg; and terminal elimination half-life was 11.2 (7.6–24.3) h.ConclusionHydromorphone (0.1 mg/kg IV bolus then IV CRI of 0.01 mg/kg/h) maintained steady-state plasma concentrations above the minimum human analgesic target in healthy Beagle dogs with minimal side effects. Further studies are needed to determine the effective plasma concentrations of hydromorphone in painful dogs.

Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioidinduced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine – 2; hydromorphone – 3; fentanyl – 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was comparedwith hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery comparedwith hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

Sophia Dobischok,1,2 Daphne Guh,2 Kirsten Marchand,2 Scott MacDonald,3 Kurt Lock,2,4 Scott Harrison,3 Julie Lajeunesse,3 Martin T Schechter,2,5 Eugenia Oviedo-Joekes2,5 1Department of Education and Counselling Psychology, McGill University, Montreal, QC, Canada; 2Centre for Advancing Health Outcomes, Providence Health Care, Vancouver, BC, Canada; 3Providence Health Care, Providence Crosstown Clinic, Vancouver, BC, Canada; 4BC Centre for Disease Control, Provincial Health Services Authority, Vancouver, BC, Canada; 5School of Population and Public Health, University of British Columbia, Vancouver, BC, CanadaCorrespondence: Eugenia Oviedo-Joekes, Centre for Advancing Health Outcomes, St. Paul’s Hospital, 575-1081 Burrard St, Vancouver, BC, V6Z 1Y6, Canada, Tel +1 604-682-2344 Ext. 62973, Fax +1-604-806-8210, Email eugenia.joekes@ubc.caPurpose: A significant portion of the economic consequences of untreated Opioid Use Disorder (OUD) relate to individuals’ involvement in the criminal justice system. The present study uncovers if treatment with iOAT is related to the number of criminal charges amongst participants, what type of crime participants were involved in, and the frequency with which participants were victims of crime. This study contributes to the body of research on the effectiveness of iOAT reducing criminal involvement.Patients and Methods: This is a secondary analysis of police record data obtained from the Vancouver Police Department over a three-year period during the Study to Assess Longer-term Opioid Medication Effectiveness clinical trial. The data was obtained from participants (N = 192) enrolled in the trial through a release of information form.Results: During the three-year period, most charges (45.6%) were property offences, and 25.5% of participants were victims of crime. Participants with no treatment prior to randomization into the SALOME trial were 2.61 (95% CI = 1.64– 4.14) more likely to have been charged with a crime than during the iOAT state.Conclusion: IOAT can reduce individuals’ involvement with the criminal justice system and is thus a crucial part of the continuum of care. Addiction should be conceptualized as a healthcare rather than criminal issue.Keywords: heroin assisted treatment, diacetylmorphine, hydromorphone, crime, charges, police

Objective Individual experience with opioids is highly variable. Some patients with acute pain do not experience pain relief with opioids, and many report no euphoria or dysphoric reactions. In this study, we describe the clinical phenotypes of patients who receive intravenous opioids. Methods This was an emergency department-based study in which we enrolled patients who received an intravenous opioid. We collected 0 to 10 pain scores prior to opioid administration and 15 minutes after. We also used 0 to 10 instruments to determine how high and how much euphoria the patient felt after receipt of the opioid. Using a cutoff point of ≥50% improvement in pain and the median score on the high and euphoria scales, we assigned each participant to one of the following clinical phenotypes: pain relief with feeling high or euphoria, pain relief without feeling high or euphoria, inadequate relief with feeling high or euphoria, and inadequate relief without feeling high or euphoria. Results A total of 713 patients were enrolled, 409 (57%) of whom reported not feeling high, and 465 (65%) reported no feeling of euphoria. Median percent improvement in pain was 37.5% (interquartile range, 12.5%–60.0%). One hundred seventy-eight participants (25%) were classified as experiencing pain relief with euphoria or feeling high, 190 (27%) experienced inadequate relief with euphoria or feeling high, 101 (14%) experienced pain relief without euphoria or feeling high, and 244 (34%) reported inadequate relief without euphoria or feeling high. Conclusion Among patients who receive intravenous opioids in the emergency department, the experiences of pain relief and euphoria are highly variable. For many, pain relief is independent of feeling high.

ObjectivesAcute pain management in patients with opioid use disorder who are maintained on methadone presents unique challenges due to high levels of opioid tolerance in this population. This randomized controlled study assessed the analgesic and abuse liability effects of escalating doses of acute intravenous (IV) hydromorphone versus placebo utilizing a validated experimental pain paradigm, quantitative sensory testing (QST).MethodsIndividuals (N = 8) without chronic pain were maintained on 80-100 mg/day of oral methadone. Participants received four IV, escalating/incremental doses of hydromorphone over 270 min (32 mg total) or four placebo doses within a session test day. Test sessions were scheduled at least one week apart. QST and abuse liability measures were administered at baseline and after each injection.ResultsNo significant differences between the hydromorphone and placebo control conditions on analgesic indices for any QST outcomes were detected. Similarly, no differences on safety or abuse liability indices were detected despite the high doses of hydromorphone utilized. Few adverse events were detected, and those reported were mild in severity.ConclusionsThe findings demonstrate that methadone-maintained individuals are highly insensitive to the analgesic effects of high-dose IV hydromorphone and may require very high doses of opioids, more efficacious opioids, or combined non-opioid analgesic strategies to achieve adequate analgesia.

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. [ABSTRACT FROM AUTHOR]

The emergency department (ED) is a frequent utilizer of alternative routes of medication administration (e.g., intranasal) for a variety of indications. Over the last several years, investigations into the use of medications via the nebulization route have greatly increased, with varying degrees of efficacy identified. This route has multiple theoretical advantages. Medications affecting bronchopulmonary function or secretions can be administered directly to the site of action, possibly utilizing a lower dose and hence minimizing side effects. It is also possible to have a faster onset of action compared with other routes, given the enhanced surface area for absorption. One group of medications that has been explored via this route of administration, and is frequently administered in EDs across the nation, is opioids, most notably fentanyl, hydromorphone, and morphine. However multiple questions exist regarding the implementation of these therapies via this route, including efficacy, dosing, and the functional aspects of medication administration that are more complex than that of more traditional routes. The intent of this review is to explore the supporting literature behind the use of nebulized opioids, most specifically fentanyl, hydromorphone, and morphine, in the ED for the treatment of acute pain presentations and provide the most up-to-date guidance for practitioners. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate antinociceptive efficacy of SC administration of hydromorphone hydrochloride and buprenorphine hydrochloride in ferrets (Mustela putorius furo). ANIMALS: 14 healthy adult ferrets (6 neutered males, 8 spayed females). METHODS: In a randomized, blind, controlled, complete crossover design, all 14 ferrets received a single, SC injection of hydromorphone low dose (0.1 mg/kg), hydromorphone high dose (0.2 mg/kg), buprenorphine low dose (0.02 mg/kg), buprenorphine high dose (0.04 mg/kg), or saline solution (0.2 mL/kg). Sedation and forelimb withdrawal latency from a noxious thermal stimulation were evaluated, and behavior was recorded for a total of 8 hours postinjection. RESULTS: Compared to saline, administration of hydromorphone at 0.2 mg/kg resulted in an estimated increase of withdrawal latencies of 7.4 seconds (95% CI, 3.2 to 11.6) at 60 minutes, of 6.6 seconds (2.4 to 10.8) at 90 minutes, of 6.0 seconds (1.8 to 10.2) at 120 minutes, of 7.0 seconds (2.9 to 11.1) at 180 minutes, and of 4.5 seconds (0.5 to 8.6) at 240 minutes. These differences were statistically significant. Hydromorphone administered at a lower dose and buprenorphine at either dose did not increase withdrawal latencies compared to saline. Based on the sedation score used in this study, signs of sedation increased over time in a similar fashion with all treatments, including saline. Erratic dysphoric-like behaviors occurred in all groups except for saline. CLINICAL RELEVANCE: SC administration of hydromorphone at a dose of 0.2 mg/kg provided antinociception from 1 to 4 hours postinjection. Further validation of sedation scores in ferrets is warranted. [ABSTRACT FROM AUTHOR]