Dose Of Hydromorphone Research Articles

Impact of Intrathecal Fentanyl on Hospital Outcomes for Patients Undergoing Primary Total Hip Arthroplasty With Neuraxial Anesthesia.

BackgroundIntrathecal opioids have been used to reduce pain after total joint arthroplasty; however, the utility of these drugs is disputed. We examined the impact of eliminating intrathecal fentanyl on outcomes for patients undergoing direct anterior approach total hip arthroplasty (THA).MethodsRetrospective review of 376 THA patients from a single institution was conducted. Univariate analysis was used to compare intraoperative medication usage and postoperative outcomes for THA patients receiving intrathecal fentanyl compared with those who did not receive intrathecal fentanyl.ResultsRecovery room pain scores were significantly lower for patients who received intrathecal fentanyl (intrathecal fentanyl 1.4 vs no 2.2, P = .001), but no difference in opioid consumption was observed (intrathecal fentanyl 9.3 milligram morphine equivalent vs no 10.5 milligram morphine equivalent, P = .200). Intraoperative use and dose of intravenous morphine, hydromorphone, and dexamethasone did not differ significantly between groups. There were no significant differences in length of stay between the groups (intrathecal fentanyl 1.1 days vs 1.1 days, P = .973), 90-day readmission, or recatherization rates between groups (readmission, intrathecal fentanyl 4.8% vs no 5.8%, P = .709; recatherization, intrathecal fentanyl 0% vs no 0.7%, P = 1.00).ConclusionThe administration of intrathecal fentanyl does not have a significant effect on early postoperative narcotic consumption, length of stay, 90-day readmissions, or recatheterization after THA with neuraxial anesthesia. Intrathecal fentanyl does not appear to improve outcomes and should not be included as a standard element of THA rapid recovery protocols.

Patients with Renal Failure Who Received a Small Dose of Hydromorphone and Presented with Neurotoxicity

Patients with Renal Failure Who Received a Small Dose of Hydromorphone and Presented with Neurotoxicity

Pharmacokinetics of hydromorphone hydrochloride after intramuscular and intravenous administration of a single dose to orange-winged Amazon parrots (Amazona amazonica).

To evaluate the pharmacokinetics of hydromorphone hydrochloride after IM and IV administration to orange-winged Amazon parrots (Amazona amazonica). 8 orange-winged Amazon parrots (4 males and 4 females). Hydromorphone (1 mg/kg) was administered once IM. Blood samples were collected 5 minutes and 0.5, 1.5, 2, 3, 6, and 9 hours after drug administration. Plasma hydromorphone concentrations were determined with liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated with a compartmental model. The experiment was repeated 1 month later with the same dose of hydromorphone administered IV. Plasma hydromorphone concentrations were > 1 ng/mL for 6 hours in 8 of 8 and 6 of 7 parrots after IM and IV injection, respectively. After IM administration, mean bioavailability was 97.6%, and mean maximum plasma concentration was 179.1 ng/mL 17 minutes after injection. Mean volume of distribution and plasma drug clearance were 4.24 L/kg and 64.2 mL/min/kg, respectively, after IV administration. Mean elimination half-lives were 1.74 and 1.45 hours after IM and IV administration, respectively. Hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with rapid plasma clearance and a large volume of distribution after IV administration in orange-winged Amazon parrots. Drug elimination half-lives were short. Further pharmacokinetic studies of hydromorphone and its metabolites, including investigation of multiple doses, different routes of administration, and sustained-release formulations, are recommended.

Evaluation of the thermal antinociceptive effects of hydromorphone hydrochloride after intramuscular administration to orange-winged Amazon parrots (Amazona amazonica).

To evaluate the thermal antinociceptive effects of hydromorphone hydrochloride after IM administration to orange-winged Amazon parrots (Amazona amazonica). 8 healthy adult parrots (4 males and 4 females). In a randomized crossover study, each bird received hydromorphone (0.1, 1, and 2 mg/kg) and saline (0.9% NaCl) solution (1 mL/kg; control) IM, with a 7-day interval between treatments. Each bird was assigned an agitation-sedation score, and the thermal foot withdrawal threshold (TFWT) was measured at predetermined times before and after treatment administration. Adverse effects were also monitored. The TFWT, agitation-sedation score, and proportion of birds that developed adverse effects were compared among treatments over time. Compared with the mean TFWT for the control treatment, the mean TFWT was significantly increased at 0.5, 1.5, and 3 hours and 1.5, 3, and 6 hours after administration of the 1- and 2-mg/kg hydromorphone doses, respectively. Significant agitation was observed at 0.5, 1.5, and 3 hours after administration of the 1 - and 2-mg/kg hydromorphone doses. Other adverse effects observed after administration of the 1- and 2-mg/kg doses included miosis, ataxia, and nausea-like behavior (opening the beak and moving the tongue back and forth). Although the 1- and 2-mg/kg hydromorphone doses appeared to have antinociceptive effects, they also caused agitation, signs of nausea, and ataxia. Further research is necessary to evaluate administration of lower doses of hydromorphone and other types of stimulation to better elucidate the analgesic and adverse effects of the drug in psittacine species.

Postoperative pain therapy with hydromorphone; comparison of patient-controlled analgesia with target-controlled infusion and standard patient-controlled analgesia: A randomised controlled trial.

The challenge of managing acute postoperative pain is the well tolerated and effective administration of analgesics with a minimum of side effects. The standard therapeutic approach is patient-controlled analgesia (PCA) with systemic opioids. To overcome problems of oscillating opioid concentrations, we studied patient-controlled analgesia by target-controlled infusion (TCI-PCA) as an alternative. To compare efficacy, safety and side effects of standard PCA with TCI-PCA for postoperative pain therapy with hydromorphone. Single-blinded, randomised trial. University Hospital, Germany from December 2013 to April 2015. Fifty adults undergoing cardiac surgery. Postoperative pain therapy on the ICU was managed with intravenous (i.v.) hydromorphone and patients randomised to TCI-PCA with target plasma concentrations between 0.8 and 10 ng ml, or PCA with bolus doses of 0.2 mg. Pain was regularly assessed using the 11-point numerical rating scale (NRS). Blood pressure, heart rate, oxygen saturation and cardiac output were continuously monitored, and adverse events were registered throughout the study. NRS pain ratings, hydromorphone doses, haemodynamic effects and side effects. NRS pain ratings, total doses of hydromorphone and haemodynamic data did not differ significantly between TCI-PCA and PCA. The number of bolus doses during PCA was significantly higher than the number of target increases during TCI-PCA (P = 0.006). The number of negative requests was also significantly higher during PCA than during TCI-PCA (P = 0.02). The respiratory rate on the first postoperative morning was 25 ± 6 min during TCI-PCA, compared with 19 ± 4 min during PCA (P = 0.022). Nausea occurred in 30% after TCI-PCA and 24% after PCA (P = 0.46). TCI-PCA was effective and well tolerated in acute postoperative pain management after cardiac surgery. Further studies are needed to evaluate this approach in clinical practice. EudraCT Number: 2013-002875-16, and ClinicalTrials.gov Identifier: NCT02035709.

Hospital Initiated Injectable Opioid Agonist Therapy for the Treatment of Severe Opioid Use Disorder: A Case Series.

Across North America, there is an unprecedented opioid overdose epidemic. Approximately 15% of individuals with severe opioid use disorder (OUD) do not benefit from opioid agonist therapy (OAT) such as buprenorphine/naloxone or methadone and are considered treatment refractory. Of those who inject, injectable OAT (iOAT), with hydromorphone or diacetylmorphine, offered in community settings has demonstrated improved retention to treatment and decreased nonprescription opioid use. This case series seeks to describe iOAT initiation and titration in a hospital setting for treatment refractory individuals with OUD and examine impacts of iOAT on leaving hospital against medical advice (AMA). A retrospective chart review of 4 patients initiated on iOAT during hospitalization at St. Paul's Hospital in Vancouver, BC was completed between July 2017 to May 2018. Outcomes of interest included: (1) dose titration schedules of hydromorphone; and (2) reports of leaving hospital AMA; and (3) continuation of iOAT in community postdischarge. Of the 4 participants, 2 were female and the mean age was 42 years. Despite a history of AMA, all participants stayed until the recommended the discharge after iOAT initiation. The average total doses of intravenous hydromorphone used during titration were: day 1: 100 mg and days 2 to 3: 200 mg. All continued iOAT in the community and one participant was readmitted within 30 days postdischarge. This case series describes a novel approach to the management of treatment refractory individuals with severe OUD during hospitalization. Prescribing iOAT in acute care settings is feasible and may reduce rates of leaving hospital AMA.

Patient controlled analgesia (PCA) vs non-PCA intravenous hydromorphone titration for severe cancer pain: A multi-center, phase III trial, HMORCT09-1.

12078 Background: The titration of opioid dosage is necessary for adequate pain relief with acceptable side effects among individuals with cancer pain. The titration process can be achieved by non-patient administration or PCA pump. The aim of this study was to evaluate the efficacy of PCA versus non-PAC titration for severe cancer pain. Methods: Patients with severe cancer pain (NRS ≥ 7/10 at rest) were randomized into PCA or non-PCA titration and stratified by opioid tolerance or intolerance. For PCA, the pump was set as no continuous dose, hydromorphone bolus dose was 10%-20% of the total equianalgesic of past 24h for opioid tolerance, or 0.5 mg for opioid intolerance. The lockout time was 15 min. For non-PCA, initial hydromorphone bolus was the same with PCA. Reassess pain at 15 min. The dose of hydromorphone was increased by 50%-100% if pain unchanged or increased, or repeated if NRS was 4-6, or continue at current dose as needed if NRS≤3. The primary endpoint was the time to successful titration (TST) - time from start to the time of pain controlled at NRS ≤ 3 in two consecutive evaluation with 15-min intervals, which was tested by K-M curve. Results: A total of 214 patients were randomized (106 in PCA, 108 in non-PCA) in 17 study sites. The most common sites of primary cancer were lung (21.03%), stomach (15.89%), colorectal (14.49%) etc. Median TSTs were 0.50h in PCA, 0.79h in non-PCA, HR 1.64 (95% CI 1.23, 2.17, P = 0.00127). In opioid tolerance, 0.50h in PCA, 1.00h in non-PCA (HR 1.92, 95% CI 1.32, 2.78, P = 0.0025). while in opioid intolerance, 0.50h in PCA and 0.50 in non-PCA (HR 1.35, 95% CI 0.88, 2.04, P = 0.162). The median dosage of hydromorphone for TST was 1.00mg (P25, P75 0.50, 2.00) in PCA, 1.50mg (P25, P75 1.00, 2.50) in non-PCA (P = 0.086). In opioid tolerance, 1.00mg (P25, P75 1.00, 2.00) in PCA, 2.00mg (P25, P75 1.00, 4.00) in non-PCA (P = 0.009). In opioid intolerance, 1.00mg (P25, P75 0.50, 2.00) in PCA and 1.00 mg (P25, P75 0.50, 2.00) non-PCA (P = 0.793). Mean patient satisfaction assessed by ESAS score was significantly superior in PCA to non-PCA (0.62±0.67 vs 1.27±0.98 for ITT, 0.66±0.66 vs 1.39±1.00 for opioid tolerance, and 0.56±0.69 vs 1.13±0.95 for opioid intolerance). Adverse events were similar in both PCA/non-PCA groups. Conclusions: PCA IV hydromorphone titration provided quicker analgesic effect, higher patients satisfaction, and a similar tolerability as compared to non-PCA administration in patients with severe cancer pain. Clinical trial information: NCT03375515 .

Single dose epidural hydromorphone in labour pain: maternal pharmacokinetics and neonatal exposure

IntroductionEpidural hydromorphone could be useful in obstetric analgesia as there is a need for a more water-soluble opioid than sufentanil or fentanyl with prolonged analgesic effect. To our knowledge, the pharmacokinetics of epidural hydromorphone has not been evaluated in parturients.Materials and methodsIn this pilot study, seven healthy parturients were given a single epidural dose of hydromorphone for labour pain. One parturient received 1.5 mg, two 0.75 mg and four 0.5 mg of hydromorphone hydrochloride. Dose was decreased due to nausea and pruritus. Hydromorphone’s effect, adverse effects and plasma concentrations were evaluated. Neonatal drug exposure was evaluated by umbilical vein and artery opioid concentration at birth. Neonatal outcomes were assessed using Apgar and the Neurologic Adaptive Capacity Score (NACS).ResultsAll patients received additional levobupivacaine doses on parturients’ requests. The first dose was requested at a median of 163 min (range 19–303 min) after hydromorphone administration. A total of 12 opioid related expected adverse events were reported by seven parturients. All newborn outcomes were uneventful. Hydromorphone’s distribution and elimination after single epidural dose seem similar to that reported for non-pregnant subjects after intravenous hydromorphone administration, but further research is required to confirm this observation.ConclusionsThe optimal dose of hydromorphone in labour pain warrants further evaluation.

Hydromorphone Unit Dose Affects Intraoperative Dosing

Although clinical factors related to intraoperative opioid administration have been described, there is little research evaluating whether administration is influenced by drug formulation and, specifically, the unit dose of the drug. The authors hypothesized that the unit dose of hydromorphone is an independent determinant of the quantity of hydromorphone administered to patients intraoperatively. This observational cohort study included 15,010 patients who received intraoperative hydromorphone as part of an anesthetic at the University of California, Los Angeles hospitals from February 2016 to March 2018. 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. On November 21, 2017, hydromorphone was reintroduced in the 2-mg unit dose. An interrupted time series analysis was performed using segmented Poisson regression with two change-points, the first representing the switch from a 2-mg to 1-mg unit dose, and the second representing the reintroduction of the 2-mg dose. The 2-mg to 1-mg unit dose change was associated with a 49% relative decrease in the probability of receiving a hydromorphone dose greater than 1 mg (risk ratio, 0.51; 95% CI, 0.40-0.66; P < 0.0001). The reintroduction of a 2-mg unit dose was associated with a 48% relative increase in the probability of administering a dose greater than 1 mg (risk ratio, 1.48; 95% CI, 1.11-1.98; P = 0.008). This observational study using an interrupted time series analysis demonstrates that unit dose of hydromorphone (2 mg vs. 1 mg) is an independent determinant of the quantity of hydromorphone administered to patients in the intraoperative period.

Prospective Association of Serum Opioid Levels and Clinical Outcomes in Patients With Cancer Pain Treated With Intrathecal Opioid Therapy.

Opioids remain the mainstay of cancer pain management but are associated with systemic toxicity. In refractory cancer pain, intrathecal therapy (ITT) is associated with improved pain control, reduced systemic side effects, and improved survival. It has been assumed that ITT decreases systemic serum opioid levels and their associated toxicity, but there are limited data to support this assumption. This study hypothesizes that serum opioid levels decrease with ITT. Secondary objectives include comparative measures of pain, bowel function, and other cancer-related symptoms. Fifty-one cancer patients undergoing ITT for cancer pain were recruited in a prospective observational study. Daily oral morphine equivalency (OME) dose, serum opioid levels, Brief Pain Inventory (BPI), MD Anderson Symptom Inventory (MDASI), and a constipation questionnaire were obtained at the time of implant, and 4 and 8 weeks postoperatively. Average baseline daily OME was 375 mg (median, 240; interquartile range, 150-405; range, 0-3160), mean serum morphine concentration was 53.7 ng/mL (n = 17), and mean oxycodone concentration was 73.7 ng/mL (n = 20). At 4 weeks, 87.5% of patients had discontinued non-IT opioids, and 53% had undetectable (<2 ng/mL) serum opioid concentrations. At 8 weeks, 92% remained off all non-IT opioids and 59% had undetectable serum opioid levels. IT morphine doses >4.2 mg/d were invariably associated with detectable serum levels; with doses <4.2 mg, morphine was undetectable in 80% of subjects. IT hydromorphone doses >6.8 mg/d were detectable in the serum. Using linear mixed model analyses, there were statistically significant decreases in the mean "worst pain," "average pain," and MD Anderson symptom severity and interference scores at 4 and 8 weeks. This change was independent of serum opioid levels; when analyzed separately, there was no difference in the pain scores of subjects with detectable serum opioid levels compared to those with undetectable levels at 4 and 8 weeks. Constipation ranked as "quite a bit" or "very much" decreased from 58.7% to 19.2% of subjects at week 4 (P < .001) and to 37.5% at 8 weeks (P = .23). A very low complication rate was observed. ITT for cancer pain was associated with a marked reduction in serum opioid concentrations, with the majority of patients having undetectable serum levels. Reducing serum opioid concentrations in cancer patients may have implications with respect to restoring bowel function, improving fatigue, and promoting the integrity of antitumor immune function and warrants further study.

Prescription Opioids induce Gut Dysbiosis and Exacerbate Colitis in a Murine Model of Inflammatory Bowel Disease.

Opioids are the most prescribed analgesics for pain in inflammatory bowel diseases [IBD]; however, the consequences of opioid use on IBD severity are not well defined. This is the first study investigating consequences of hydromorphone in both dextran sodium sulphate [DSS]-induced colitis and spontaneous colitis (IL-10 knockout [IL-10-/-]) mouse models of IBD. To determine the consequences of opioids on IBD pathogenesis, wild-type [WT] mice were treated with clinically relevant doses of hydromorphone and colitis was induced via 3% DSS in drinking water for 5 days. In parallel we also determined the consequences of opioids in a spontaneous colitis model. Hydromorphone and DSS independently induced barrier dysfunction, bacterial translocation, disruption of tight junction organisation and increased intestinal and systemic inflammation, which were exacerbated in mice receiving hydromorphone in combination with DSS. Hydromorphone + DSS-treated mice exhibited significant microbial dysbiosis. Predictive metagenomic analysis of the gut microbiota revealed high abundance in the bacterial communities associated with virulence, antibiotic resistance, toxin production, and inflammatory properties. Hydromorphone modulates tight junction organisation in a myosin light chain kinase [MLCK]-dependent manner. Treatment with MLCK inhibitor ML-7 ameliorates the detrimental effects of hydromorphone on DSS-induced colitis and thus decreases severity of IBD. Similarly, we demonstrated that hydromorphone treatment in IL-10-/- mice resulted in accelerated clinical manifestations of colitis compared with control mice. Opioids used for pain management in IBD accelerate IBD progression by dysregulation of the gut microbiota, leading to expansion of pathogenic bacteria, translocation of bacteria, immune deregulation and sustained inflammation.

Opioid-related respiratory and gastrointestinal adverse events in patients with acute postoperative pain: prevalence, predictors, and burden

Opioid-induced respiratory depression (OIRD) and postoperative nausea and vomiting (PONV) are challenging, resource-intensive, and costly opioid-related adverse events (ORAEs). Utilizing the Premier Healthcare Database, we identified patients > 18 years old, who underwent at least one surgical procedure of interest (i.e., cardiothoracic/vascular, general/colorectal, obstetric/gynecologic, orthopedic, or urologic), and received at least one dose of intravenous morphine, hydromorphone, or fentanyl for acute postoperative pain. The incidence of OIRD and PONV using ICD-9 codes, factors influencing these AEs, length of stay (LOS) and related costs were analyzed. Among 592,127 inpatient stays, rates of respiratory depression ranged from 3% (obstetric/gynecologic) to 17% (cardiothoracic/vascular) and nausea/vomiting from 44% (obstetric/gynecologic) to 72% (general/colorectal). Increased odds of OIRD were associated with older age (cardiothoracic/vascular, general/colorectal, obstetric/gynecologic); obesity, respiratory conditions, and sleep apnea (all surgery groups); opioid dose (cardiothoracic/vascular, general/colorectal, orthopedic); and sedative use after day 1. Increased odds of PONV were associated with younger age, female sex, and major disease severity. When respiratory depression or nausea/vomiting was present versus absent, LOS was significantly longer, and hospital costs were higher. In this analysis, OIRD and PONV were more prevalent than previously reported, were associated with identifiable risk factors, and had substantial effects on resource utilization and costs.

Patient controlled analgesia (PCA) versus non-PCA intravenous hydromorphone titration for severe cancer pain: A randomized, controlled, multicenter, phase III trial, HMORCT09-1.

TPS11635 Background: The opioid dose for an individual with cancer pain to provide adequate relief of pain with an acceptable degree of side effects is variable. Opioid titration is a process to obtain the tailored dose. Conventional titration is administered by a clinician or nurse. PCA is that patients control cancer pain by self-administration of intravenous opioids using programmable pump. The aim of our study is to evaluate the efficacy of PCA titration versus conventional titration intravenously for severe cancer pain (10-point numerical rating scale, NRS ≥ 7). Injectable Hydromorphone was selected as pharmaceutical analgesics, which works as well as morphine and oxycodone and had similar side effects. Methods: This is currently enrolling patients (n=230) with severe cancer pain during previous 24 hours. Patients are randomized 1:1 and stratified by opioid intolerance or opioid tolerance into PCA or non-PCA titration. PCA titration using programmable pump: bolus hydromorphone at 0.5mg (for opioid intolerance) or hydromorphone dose equivalent to 10% to 20% of the total opioid taken in the previous 24 hours with a lockout time 15 minutes (for opioid tolerance) was administered by the patients educated. No basal infusion was set in the pump. Non-PCA titration administered by a nurse or clinician: Initial hydromorphone doses were same with PCA titration. Reassess pain at 15 minutes. Increased dose of hydromorphone by 50%-100% if pain unchanged or increased, or repeat same dose if pain decreased to NRS 4-6, or continue at current effective dose as needed over initial 24 hours. The primary endpoint is the time needed to successful titration was defined the time from the first dose of hydromorphone after randomization to achieve satisfied pain control. The satisfied pain control was defined NRS pain score ≤ 3 at rest in at least 2 consecutive assessment (15 minutes interval). The time needed to successful titration was extended to achieve satisfied pain control again if NRS pain score ≥ 7 after satisfied pain control within 24 hours. The failure of successful titration was defined that satisfied pain control does not achieve within 24 hours. Secondary endpoints include the percentage of patients titrated successfully, the mean NRS pain score of 24 hours, the total dose of hydromorphone titrated, and adverse events. Clinical trial information: NCT03375515.

Abstract 249: Understanding the Patient Experience of Pain and Discomfort During Cardiac Catheterization

Background: Patient centeredness is an essential component of high-quality care, yet little is published regarding the patient experience during procedures performed in the cardiac catheterization lab. Available literature focuses on the safe delivery of sedation, but does not address patient-reported satisfaction, comfort, or procedural experience. Further delineation of how procedural factors impact the patient experience is needed. Methods and Results: We conducted a retrospective, exploratory analysis of adult cardiac catheterization outpatients receiving nurse-administered, physician-prescribed procedural sedation (benzodiazepine and/or opioids) between April-June, 2017. Data were abstracted from the procedural database, EHR and Press Ganey© surveys. Patients (n=375) had a mean age of 63, were male 60% (226/375), White 73% (271/375), and overweight / obese (mean BMI = 29). Procedural sedation was given in 93% (348/375) of cases. Press Ganey© results showed good satisfaction with pain control (&gt;75 th percentile) and staff concern for comfort in all patients. There was no significant difference in pre- and post-procedural patient reported pain scores. The median patient received 1.63 doses of midazolam with either 1.48 doses of fentanyl or 1.33 doses of hydromorphone. Median time interval between administration of initial sedative dose and local anesthetic was 6.2 minutes. Patients with longer intervals had less frequent dosing (p&lt;0.001) and less total procedural sedation (p&lt;0.001). Adjusting for demographic and procedural characteristics, trainee involvement (p=0.001), older age (p=0.002) and longer time intervals (p=&lt;0.001) between dosing and local anesthetic were associated with decreased frequency and total dose. Conclusions: Extended duration of sedation intervals was associated with lower overall sedation administration with similar patient satisfaction. Optimizing processes for administering peri-procedural sedation may allow for less total medication without impacting patient experience.

(289) Conditioned Pain Modulation in Buprenorphine-Maintained Patients with Opioid Use Disorder

The number of persons on buprenorphine maintenance for opioid use disorder (OUD) is rising and these patients often have chronic pain. It is not clear whether the endogenous analgesic system, which is often dysregulated in chronic pain patients, is affected by buprenorphine maintenance. Conditioned pain modulation (CPM) can evaluate endogenous analgesia; CPM is tested by applying a primary noxious stimulus alone and then simultaneously with a conditioning noxious stimulus on a remote body part. An efficient CPM results in an increase in primary pain threshold in the presence of the conditioning stimulus. A less efficient CPM is pro-nociceptive and results in lower primary pain threshold in the presence of the conditioning stimulus. This study assessed CPM in persons without chronic pain maintained on buprenorphine. CPM was tested by measuring pressure pain threshold at baseline and while undergoing a cold pressor test. Further, this study examined whether adjunct hydromorphone and/or buprenorphine, compared to placebo, effected CPM. Participants (N=13) with OUD who were maintained on 12mg or 16mg buprenorphine performed three study sessions, at least one week apart, where they underwent CPM at baseline and after cumulative doses of 32mg IV hydromorphone, 32mg IV buprenorphine, or placebo. Thirty-one percent of participants displayed less efficient CPM in at least one session prior to drug administration based on lower pressure pain threshold during cold-pressor testing compared to baseline. There were no significant differences in the proportion of individuals with less efficient CPM following 32mg IV hydromorphone (69%), 32mg buprenorphine (54%), or placebo (62%) (p=0.779). Results suggest that some buprenorphine-maintained individuals experience less efficient CPM. High doses of hydromorphone or buprenorphine did not improve CPM compared to placebo. Non-opioid analgesic strategies should be developed to address chronic pain in persons maintained on buprenorphine. Study medications provided by Indivior, Inc.

Postoperative Analgesic Effects of Different Doses of Epidural Hydromorphone Coadministered with Ropivacaine after Cesarean Section: A Randomized Controlled Trial

Purpose Single dose of epidural hydromorphone has been introduced to serve as an alternative method for postcesarean section analgesia. However, optimal dose of epidural hydromorphone remains unknown. Hence, we evaluated and compared the analgesic and adverse effects of postoperative different doses of epidural hydromorphone coadministered with ropivacaine after cesarean section. Methods Eighty term parturients with elective cesarean section under epidural anesthesia were allocated into four groups. Epidural analgesia was administered with an epidural bolus of either 0 mg (group H0), or 0.2 mg (group H1), or 0.4 mg (group H2), or 0.6 mg (group H3) hydromorphone coadministered with ropivacaine. The primary outcome was the visual analogue pain scores (VAPSs) and rescue opioid consumption (PCIA with sulfentanil) in 24 hours. Adverse effects such as respiratory depression, pruritus, nausea, and vomiting were recorded. Results The VAPSs of group H1 at 2, 4, 6, 12 h and 24 h after surgery was similar to group H0. The VAPSs of group H2 at 4 and 6 h postoperatively were significantly decreased when compared to group H0. But, the VAPSs of group H2 at 2, 12, and 24 h postoperatively were similar to those of group H0. The VAPSs of group H3 at 4, 6, 12 h, and 24 h after surgery were significantly decreased when compared to those of group H0. The total sulfentanil consumption in 24 hours was 90 ± 26 μg in group H0, 75 ± 29 μg in group H1, 54 ± 32 μg in group H2, and 15 ± 16 μg in group H0. Adverse effects were comparable in the four groups. Conclusions Epidural administration of 0.6 mg hydromorphone coadministered with ropivacaine after cesarean section provided satisfactory pain relief with less sulfentanil consumption. This trial is registered with ChiCTR-IPR-16010026.

Adverse Events During Treatment Induction With Injectable Diacetylmorphine and Hydromorphone for Opioid Use Disorder.

The present study aims to describe a 3-day induction protocol for injectable hydromorphone (HDM) and diacetylmorphine (DAM) used in 3 Canadian studies and examine rates of opioid-related overdose and somnolence during this induction phase. The induction protocol and associated data on opioid-related overdose and somnolence are derived from 2 clinical trials and one cohort study conducted in Vancouver and Montreal (2005-2008; 2011-2014; 2014-2018). In this analysis, using the Medical Dictionary for Regulatory Activities coding system we report somnolence (ie, drowsiness, sleepiness, grogginess) and opioid overdose as adverse events. Overdoses requiring intervention with naloxone are coded as severe adverse events. Data from the 3 studies provides a total of 1175 induction injections days, with 700 induction injection days for DAM, and 475 induction injection days for HDM. There were 34 related somnolence and adverse event (AE) overdoses (4.899 per 100 injection days) in DAM and 6 (1.467 per 100 days) in HDM. Four opioid overdoses requiring naloxone (0.571 per 100 injection days) were registered in DAM and 1 in HDM (0.211 per 100 injection days), all safely mitigated onsite. The first week maximum daily dose patients received were on average 433.62 mg [standard deviation (SD) = 137.92] and 223.26 mg (SD = 68.06) for DAM and HDM, respectively. A 3-day induction protocol allowed patients to safely reach high doses of injectable hydromorphone and diacetylmorphine in a timely manner. These findings suggest that safety is not an evidence-based barrier to the implementation of treatment with injectable hydromorphone and diacetylmorphine.

Pharmacokinetics of subcutaneously administered hydromorphone in bearded dragons (Pogona vitticeps) and red-eared slider turtles (Trachemys scripta elegans)

ObjectiveTo determine pharmacokinetic dosing strategy in bearded dragons (Pogona vitticeps) and red-eared sliders (Trachemys scripta elegans) based on two subcutaneously (SC) administered doses of hydromorphone (0.5 and 1.0 mg kg−1). Study designRandomized crossover study. AnimalsSix healthy adult bearded dragons, seven healthy adult red-eared slider turtles. MethodsHydromorphone (0.5 and 1.0 mg kg−1; 2 mg mL−1) was administered SC dorsolateral to the scapulae in the bearded dragons and between the head and thoracic limb of the red-eared slider turtles. Blood was collected for hydromorphone plasma concentration analysis from the ventral tail vein in bearded dragons and subcarapacial sinus in turtles before (time 0) hydromorphone administration and at 0.5, 1, 6, 12 and 24 hours. ResultsThe half-life of hydromorphone administered at 0.5 and 1.0 mg kg−1 was 2.54 and 3.05 hours in bearded dragons and 2.67 and 2.01 hours in red-eared sliders, respectively. The maximum plasma concentrations for 0.5 and 1.0 mg kg−1 were 142 and 369 ng mL−1 in bearded dragons and 1610 and 5142 ng mL−1 in red-eared sliders, respectively. Peak plasma concentrations were detected at 30 minutes for both species. Hydromorphone administered at both dosages provided plasma concentrations of 13–14 ng mL−1 for at least 24 hours in bearded dragons and of 5–6 ng mL−1 for at least 12 hours in red-eared sliders. Clinical sedation was observed for up to 1 hour posthydromorphone (1.0 mg kg−1) administration for five of six bearded dragons characterized by low body carriage and decreased response to stimuli. No evidence of clinical sedation was observed in red-eared sliders at either dose. Conclusions and clinical relevanceRecommended dosing strategy for hydromorphone is 0.5 mg kg−1 administered SC every 24 hours in bearded dragons and every 12–24 hours in red-eared sliders.

Postprocedure Intravenous Patient-Controlled Analgesia Compared to Epidural Patient-Controlled Analgesia Use after Uterine Fibroid Embolization: A Clinical Audit.

Purpose:Postprocedure epidural analgesia has a proven benefit over intravenous (i.v.) analgesia for pain management, but has not yet been demonstrated for uterine fibroid embolization (UFE). The objectives of this clinical audit were to determine if epidural patient-controlled analgesia (PCA) was beneficial to patient outcome as compared to i.v. PCA in decreasing parenteral opioid requirements and its associated side effects and determine if there is a difference in required oral opioids after the PCA is stopped.Materials and Methods:This manuscript audited postprocedural pain management of 51 patients after UFE was performed. 20 patients received an i.v. PCA for post-UFE pain control and 31 received an epidural PCA for post-UFE pain control. Total hydromorphone dose, the frequency of anti-nausea medication use, the frequency of anti-pruritus medication use, and patient pain satisfaction data was collected.Results:Total hydromorphone dose administered to patients post-UFE using epidural PCA was significantly less than patients using an i.v. PCA (P = 0.001). However, the frequency of nausea and pruritus between the two groups did not achieve statistical significance with (P = 0.663) and (P = 0.639) respectively.Conclusion:Our clinical audit found that parenteral opioid requirements administered after UFE can be significantly reduced by using epidural PCA instead of i.v. PCA. However, we found no statistically significant difference in medication related side effects or oral opioid use thereafter.

Analgesic Effects of Hydromorphone versus Buprenorphine in Buprenorphine-maintained Individuals

Managing acute pain in buprenorphine-maintained individuals in emergency or perioperative settings is a significant challenge. This study compared analgesic and abuse liability effects of adjunct hydromorphone and buprenorphine using quantitative sensory testing, a model of acute clinical pain, in persons maintained on 12 to 16 mg sublingual buprenorphine/naloxone. Participants (N = 13) were enrolled in a randomized within-subject, double-blind, placebo-controlled three-session experiment. Each session used a cumulative dosing design with four IV injections (4, 4, 8, and 16 mg of hydromorphone or 4, 4, 8, and 16 mg of buprenorphine); quantitative sensory testing and abuse liability assessments were measured at baseline and after each injection. The primary analgesia outcome was change from baseline cold pressor testing; secondary outcomes included thermal and pressure pain testing, as well as subjective drug effects and adverse events. A significant two-way interaction between study drug condition and dose was exhibited in cold pressor threshold (F10,110 = 2.14, P = 0.027) and tolerance (F10,110 = 2.69, P = 0.006). Compared to after placebo, participants displayed increased cold pressor threshold from baseline after cumulative doses of 32 mg of IV hydromorphone (means ± SD) (10 ± 14 s, P = 0.035) and 32 mg of buprenorphine (3 ± 5 s, P = 0.0.39) and in cold pressor tolerance after cumulative doses of 16 mg (18 ± 24 s, P = 0.018) and 32 mg (48 ± 73 s, P = 0.041) IV hydromorphone; cold pressor tolerance scores were not significant for 16 mg (1 ± 15 s, P = 0.619) or 32 mg (7 ± 16 s, P = 0.066) buprenorphine. Hydromorphone and buprenorphine compared with placebo showed greater ratings on subjective measures of high, any drug effects, good effects, and drug liking. Adverse events were more frequent during the hydromorphone compared with buprenorphine and placebo conditions for nausea, pruritus, sedation, and vomiting. In this acute clinical pain model, high doses of IV hydromorphone (16 to 32 mg) were most effective in achieving analgesia but also displayed higher abuse liability and more frequent adverse events. Cold pressor testing was the most consistent measure of opioid-related analgesia.