Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns.

Understanding the intricate relationship between cancer clinicopathological features and anesthetics dosage is crucial for optimizing patient outcomes and safety during surgery. This retrospective study investigates this relationship in patients with non-small cell lung cancer (NSCLC) undergoing video-assisted thoracic surgery (VATS). A comprehensive analysis of medical records was undertaken for NSCLC patients who underwent VATS with intravenous compound inhalation general anesthesia. Patients were categorized based on histological, chemotherapy, radiotherapy, and epidural anesthesia factors. Statistical analysis was performed to compare the differences between the groups. The results revealed compelling insights. Specifically, patients with lung adenocarcinoma (LUAD) undergoing VATS exhibited higher dosages of rocuronium bromide and midazolam during general anesthesia, coupled with a shorter post-anesthesia care unit (PACU) stay compared to those with squamous cell carcinoma (sqCL). Furthermore, chemotherapy patients undergoing VATS demonstrated diminished requirements for phenylephrine and remifentanil in contrast to their non-chemotherapy counterparts. Similarly, radiotherapy patients undergoing VATS demonstrated a decreased necessity for rocuronium bromide compared to non-radiotherapy patients. Notably, patients who received epidural anesthesia in combination with general anesthesia manifested reduced hydromorphone requirements and prolonged hospital stays compared to those subjected to general anesthesia alone. In conclusion, the findings from this study indicate several important observations in diverse patient groups undergoing VATS. The higher dosages of rocuronium bromide and midazolam in LUAD patients point to potential differences in drug requirements among varying lung cancer types. Additionally, the observed shorter PACU stay in LUAD patients suggests a potentially expedited recovery process. The reduced anesthetic requirements of phenylephrine and remifentanilin chemotherapy patients indicate distinct responses to anesthesia and pain management. Radiotherapy patients requiring lower doses of rocuronium bromide imply a potential impact of prior radiotherapy on muscle relaxation. Finally, the combination of epidural anesthesia with general anesthesia resulted in reduced hydromorphone requirements and longer hospital stays, suggesting the potential benefits of this combined approach in terms of pain management and postoperative recovery. These findings highlight the importance of tailoring anesthesia strategies for specific patient populations to optimize outcomes in VATS procedures.

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.

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.

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.

Patient-Controlled Subcutaneous Analgesia with Hydromorphone versus Oral Oxycontin for Opioid Titration of Cancer Pain: A Prospective Multicenter Randomized Trial.

Background: Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain. Patients and Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST). Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5-11.5] hours vs.16.0 [95% CI:11.5-22.5] hours; p<0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0-3.5) than in the oxycontin group.(3.0; 2.5-4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5-3.0) vs 4.5;3.0-6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32). Conclusion: Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p<0.001), without significantly increasing adverse events (p=0.32).

Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs.

Introduction: Dosing 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. Methods: A 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. Results: A 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. Conclusion: Hydromorphone (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.

Gastrointestinal adverse effects associated with the use of intravenous oliceridine compared with intravenous hydromorphone or fentanyl in acute pain management utilizing adjusted indirect treatment comparison methods.

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 opioid-induced 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 compared with 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 compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.

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.

Subcutaneous hydromorphone hydrochloride provides antinociception with transient adverse effects in four-toed hedgehogs (Atelerix albiventris).

OBJECTIVE: To evaluate the efficacy and safety of hydromorphone administered SC in four-toed hedgehogs (Atelerix albiventris). ANIMALS: 12 healthy adult hedgehogs. METHODS: Hedgehogs underwent 2 randomized, blinded, placebo-controlled, complete crossover studies. Hind limb withdrawal latencies in response to an acute thermal noxious stimulus were measured to evaluate the antinociceptive efficacy of hydromorphone. Baseline latencies were obtained prior to injection and collected again at 0.5, 1, 2, 4, and 6 hours following injection. Based on pilot studies, single doses of SC hydromorphone at 0.15 and 0.3 mg/kg were evaluated for efficacy in crossover trials. Safety of single (0.15 and 0.3 mg/kg) and multiple doses of hydromorphone (0.3 mg/kg, SC, q 4 h, for 3 doses) was also assessed. In addition to monitoring behavior during latency measurements, animals were evaluated for overt sedation and daily changes in food intake, body weight, and running wheel activity for 6 days after injection to evaluate for adverse effects. RESULTS: Hydromorphone at 0.15 mg/kg provided antinociception lasting < 4 hours, and 0.3 mg/kg provided antinociception lasting < 6 hours. Hydromorphone produced transient abnormal behaviors at both doses, including vocalization, chewing motions of the jaw, and paw raising. There were no statistically significant differences in body weight or running wheel activity between treatments for single or multiple doses of hydromorphone. Three doses of 0.3 mg/kg hydromorphone (q 4 h) produced a statistically significant decrease (median, -9.7%; range, -64% to 10%) in 6-day total food intake. CLINICAL RELEVANCE: Subcutaneous hydromorphone (0.15 to 0.3 mg/kg) can be used for short-term antinociception with transient adverse effects in hedgehogs.

Hydromorphone hydrochloride preconditioning combined with postconditioning attenuates myocardial ischemia/reperfusion injury in rats by improving mitochondrial function and activating the PI3K/Akt signaling pathway.

Thrombolytic therapy or percutaneous coronary intervention for myocardial infarction often cause myocardial ischemia/reperfusion injury (MIRI) and poor prognosis of patients. This study aimed to explore the protective effect and potential mechanism of hydromorphone hydrochloride (HH) on MIRI. Fifty Sprague-Dawley male rats were randomly divided into Sham group, I/R group, HH-pre group, HH-post group, and HH-pre + post group. Except Sham group, MIRI models were established by ligating and relaxing the left anterior descending coronary artery, followed by tail vein injection of HH (0.3 µmol/L) 10 min before ligation (HH-pre group), 10 min after reperfusion (HH-post group), and twice at the above two time points (HH-pre + post group). After intervention, the cardiac function of rats was evaluated by echocardiography, and the levels of myocardial injury markers, oxidative stress indicators, and mitochondrial function indicators were detected. Next, the myocardial infarction area was evaluated by 2,3,5-triphenyltetrazolium chloride staining, mitochondrial biogenesis, and phosphoinositide 3 kinase (PI3K)/protein kinase B (Akt) signaling pathway by western blot. Compared with the I/R group, HH intervention improved cardiac function, decreased myocardial infarction area, reduced serum myocardial injury markers, alleviated oxidative stress, improved mitochondrial function, up-regulated mitochondrial biogenesis, and activated PI3K/Akt signaling pathway. Moreover, the HH-pre + post group was superior to the HH-pre and HH-post groups in the above aspects. Collectively, HH had protective effect on MIRI rats, and HH preconditioning combined with postconditioning showed optimal efficacy. Such efficacy may be achieved by promoting mitochondrial biogenesis to improve mitochondrial function and reduce oxidative stress, and activating the PI3K/Akt signaling pathway.

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).

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.

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.

[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.

Variability in opioid conversion calculators in critically ill children transitioned from fentanyl to hydromorphone.

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.

Patient Controlled Subcutaneous Analgesia of Hydromorphone Versus Morphine to Treat Moderate and Severe Cancer Pain: A Randomized Double-Blind Controlled Trial.

CONTEXT: 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. OBJECTIVES: To explore the short-term efficacy and safety of PCSA elicited by hydromorphone for moderate to severe cancer pain. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

A case of fatal overdose involving both hydromorphone and kratom.

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.

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.

The Impact of Injectable Opioid Agonist Treatment (iOAT) on Involvement in Criminalized Activities: A Secondary Analysis from a Clinical Trial in Vancouver, BC.

Purpose: 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.

Comparing Post-operative Opioid Consumption before and after a Patient-Controlled Analgesia Shortage: A Re-evaluation of Safety and Effectiveness.

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.