Erector spinae plane block did not improve postoperative pain-related outcomes and recovery after video-assisted thoracoscopic surgery : a randomised controlled double-blinded multi-center trial.

INTRODUCTION: There is a sizable niche for a minimally invasive analgesic technique that could facilitate ambulatory video-assisted thoracoscopic surgery (VATS). Our study aimed to determine the analgesic potential of a single-shot erector spinae plane (ESP) block for VATS. The primary objective was the total hydromorphone consumption with patient-controlled analgesia (PCA) 24 h after surgery. METHODS: We conducted a randomized, controlled, double-blind study with patients scheduled for VATS in two major university-affiliated hospital centres. We randomized 52 patients into two groups: a single-shot ESP block using bupivacaine or an ESP block with normal saline (control). We administered a preoperative and postoperative (24 h) quality of recovery (QoR-15) questionnaire and assessed postoperative pain using a verbal numerical rating scale (VNRS) score. We evaluated the total standardized intraoperative fentanyl administration, total postoperative hydromorphone consumption (PCA; primary endpoint), and the incidence of adverse effects. RESULTS: There was no difference in the primary objective, hydromorphone consumption at 24 h (7.6 (4.4) mg for the Bupivacaine group versus 8.1 (4.2) mg for the Control group). Secondary objectives and incidence of adverse events were not different between the two groups at any time during the first 24 h following surgery. CONCLUSION: Our multi-centre randomized, controlled, double-blinded study found no advantage of an ESP block over placebo for VATS for opioid consumption, pain, or QoR-15 scores. Further studies are ongoing to establish the benefits of using a denser block (single-shot paravertebral with a continuous ESP block), which may provide a better quality of analgesia.

Efficacy of bilateral catheter superficial parasternal intercostal plane blocks using programmed intermittent bolus for opioid-sparing postoperative analgesia in cardiac surgery with sternotomy: A randomized, double-blind, placebo-controlled trial.

STUDY OBJECTIVE: This study investigated whether catheter superficial parasternal intercostal plane (SPIP) blocks, using a programmed intermittent bolus (PIB) with ropivacaine, could reduce opioid consumption while delivering enhanced analgesia for a period exceeding 48 h following cardiac surgery involving sternotomy. DESIGN: A double-blind, prospective, randomized, placebo-controlled trial. SETTING: University-affiliated tertiary care hospital. PATIENTS: 60 patients aged 18 or older, scheduled for cardiac surgery via sternotomy. INTERVENTIONS: The patients were randomly assigned in a 1:1 ratio to either the ropivacaine or saline group. After surgery, patients received bilateral SPIP blocks for 48 h with 0.4% ropivacaine (20 mL per side) for induction, followed by bilateral SPIP catheters using PIB with 0.2% ropivacaine (8 mL/side, interspersed with a 2-h interval) or 0.9% normal saline following the same administration schedule. All patients were administered patient-controlled analgesia with hydromorphone. MEASUREMENTS: The primary outcome was the cumulative morphine equivalent consumption during the initial 48 h after the surgery. Secondary outcomes included postoperative pain assessment using the Numeric Rating Scale (NRS) at rest and during coughing at designated intervals for three days post-extubation. Furthermore, recovery indicators and ropivacaine plasma levels were diligently documented. MAIN RESULTS: Cumulative morphine consumption within 48 h in ropivacaine group decreased significantly compared to saline group (25.34 ± 31.1 mg vs 76.28 ± 77.2 mg, respectively; 95% CI, -81.9 to -20.0, P = 0.002). The ropivacaine group also reported lower NRS scores at all recorded time points (P < 0.05) and a lower incidence of nausea and vomiting than the saline group (3/29 vs 12/29, respectively; P = 0.007). Additionally, the ropivacaine group showed significant improvements in ambulation (P = 0.018), respiratory exercises (P = 0.006), and self-reported analgesia satisfaction compared to the saline group (P = 0.016). CONCLUSIONS: Bilateral catheter SPIP blocks using PIB with ropivacaine reduced opioid consumption over 48 h, concurrently delivering superior postoperative analgesia in adult cardiac surgery with sternotomy.

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.

Relationship between opioid cross-tolerance during buprenorphine stabilization and return to opioid use during buprenorphine dose tapering.

RATIONALE: Opioid injection drug use (IDU) has been linked to a more severe pattern of use (e.g. tolerance, overdose risk) and shorter retention in treatment, which may undermine abstinence attempts. OBJECTIVES: This secondary data analysis of four human laboratory studies investigated whether current opioid IDU modulates subjective abuse liability responses to high-dose hydromorphone during intermediate-dose buprenorphine stabilization (designed to suppress withdrawal but allow surmountable agonist effects), and whether hydromorphone response magnitude predicts latency of return to opioid use during buprenorphine dose-tapering. METHODS: Regular heroin users not currently seeking treatment (n = 54; 29 current injectors, 25 non-injectors) were stabilized on 8-mg/day sublingual buprenorphine and assessed for subjective responses (e.g. 'liking', craving) to hydromorphone 24-mg intramuscular challenge (administered 16-hr post-buprenorphine) under randomized, double-blinded, controlled conditions. A subgroup (n = 35) subsequently completed a standardized 3-week outpatient buprenorphine dose-taper, paired with opioid-abstinent contingent reinforcement, and were assessed for return to opioid use based on thrice-weekly urinalysis and self-report. RESULTS: During buprenorphine stabilization, IDU reported lower 'liking' of buprenorphine and post-hydromorphone peak 'liking', 'good effect' and 'high' compared to non-IDU. Less hydromorphone peak increase-from-baseline in 'liking' (which correlated with less hydromorphone-induced craving suppression) predicted significantly faster return to opioid use during buprenorphine dose-tapering. CONCLUSIONS: In these buprenorphine-stabilized regular heroin users, IDU is associated with attenuated 'liking' response (more cross-tolerance) to buprenorphine and to high-dose hydromorphone challenge and, in turn, this cross-tolerance (but not IDU) predicts faster return to opioid use. Further research should examine mechanisms that link cross-tolerance to treatment response.

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.

Effectiveness of perioperative low-dose esketamine infusion for postoperative pain management in pediatric urological surgery: a prospective clinical trial.

BACKGROUND: Postoperative pain is common in pediatric urological surgery. The study assess the impact of perioperative intravenous infusion of low-dose esketamine on postoperative pain in pediatric urological surgery. METHODS: Pediatric patients (n = 80) undergoing urological surgery were randomized into four groups. Patients in the control group were administered an analgesic pump containing only hydromorphone at a dose of 0.1 mg/kg (Hydromorphone Group 1, H1) or 0.15 mg/kg (Hydromorphone Group 2, H2). Patients in the experimental group were injected intravenously with 0.3 mg/kg of esketamine (Esketamine group 1, ES1) or equal volume of saline (Esketamine Group 2, ES2) during anesthesia induction. Esketamine 1.0 mg/kg and hydromorphone 0.1 mg/kg were added to the analgesic pump. Face, Leg, Activity, Crying, and Comfort (FLACC) scale or the Numerical Rating Scale (NRS) and adverse effects were recorded at 2, 6, 24, and 48 h postoperatively. Additionally, total and effective PCA button presses were recorded. RESULTS: In comparison to the H1 group, the pain scores were notably reduced at all postoperative time points in both the ES1 and H2 groups. The ES2 group exhibited lower pain scores only at 24 and 48 h postoperatively. When compared to the H2 group, there were no significant differences in pain scores at various postoperative time points in the ES2 group. However, the ES1 group demonstrated significantly lower pain scores at 6, 24 and 48 h postoperatively, and these scores were also significantly lower than those observed in the ES2 group. The total and effective number of PCA button presses in the ES1, ES2 and H2 group were lower than that in the H1 group (P < 0.001). The incidence of adverse effects within 48 h after surgery was 15% in ES1, 22% in ES2, 58% in H1, and 42% in H2, respectively (P = 0.021). CONCLUSIONS: The use of low-dose esketamine infusion in analgesia pump can effectively alleviates postoperative pain in pediatric urological patients, leading to a significant reduction in the number of analgesic pump button press. The combined approach of perioperative anesthesia induction and analgesia pump administration is recommended for optimal pain management in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry- ChiCTR2300073879 (24/07/2023).

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.

Cancer-related breathlessness: opioids other than morphine - comprehensive literature review.

INTRODUCTION: Although there is low-quality evidence, there has been an increase in publications on the experience of evaluating and managing cancer-related breathlessness using opioids other than morphine. METHODS: The author conducted a non-systematic literature review in the PubMed/Medline and Embase until 4 October 2022. Eligible studies have evaluated the efficacy of opioids other than morphine for cancer-related breathlessness. Studies focused on sedation, anaesthesia, paediatric patients, opioid toxicity or basic research were excluded. Reviews/meta-analyses and non-English language publications were also excluded. RESULTS: A total of 1556 records were identified, of which 23 studies including 469 patients who were treated with fentanyl (n=223), oxycodone (n=171) and hydromorphone (n=75) were considered eligible. Six phase II randomised clinical trials (RCTs), four observational studies and four case reports of fentanyl were found. For breathlessness on exertion, fentanyl yielded promising results, but no RCT showed significant superiority of fentanyl to placebo or morphine. For terminal breathlessness, three RCTs, five non-randomised or observational studies and one case report on oxycodone or hydromorphone were found. Although the results of the observational studies suggested that oxycodone and hydromorphone might be effective alternatives to morphine, the superiority over placebo or non-inferiority to morphine had not been demonstrated in the RCTs. CONCLUSION: As an alternative to morphine, the author recommends fentanyl for breathless crisis or breathlessness on exertion, and oxycodone or hydromorphone for terminal breathlessness in advanced cancer. Larger and well-designed studies based on firm research policies are needed to confirm this current knowledge.

Opioid Switch Dosing in Chronic Cancer Pain: A Prospective Longitudinal Study.

Background: Opioid switching is common, however, conversion tables have limitations. Guidelines suggest postswitch dose reduction, yet, observations show opioid doses may increase postswitch. Objectives: To document the opioid conversion factor postswitch in cancer, and whether pain and adverse effect outcomes differ between switched opioid groups. Design/Setting: This multicenter prospective longitudinal study included people with advanced cancer in Australia. Clinical data (demographics, opioids) and validated instruments (pain, adverse effects) were collected twice, seven days apart. Results: Opioid switch resulted in dose increase (median oral morphine equivalent daily dose 90 mg [interquartile range {IQR} 45-184] to 150 mg [IQR 79-270]), reduced average pain (5.1 [standard deviation {SD} 1.7] to 3.8 [SD 1.6]), and reduced adverse effects. Hydromorphone dose increased 2.5 times (IQR 1.0-3.6) above the original conversion factor used. Conclusions: Opioid switching resulted in overall dose increase, particularly when switching to hydromorphone. Higher preswitch dosing may require higher dose conversion ratios. Dose reduction postswitch risks undertreatment and may not be always appropriate.

Comparison of the Effects of OPRM1 A118G Polymorphism Using Different Opioids: A Prospective Study.

CONTEXT: µ-opioid receptor gene (OPRM1) A118G polymorphism (rs1799971) causes loss of N-glycosylation sites at the extracellular domain of µ-opioid receptors. G-allele carriers show a limited response to morphine; however, studies investigating the impact of A118G polymorphism on the efficacy of opioids other than morphine are limited. OBJECTIVE: To compare the impact of A118G polymorphism on the efficacy of various opioids. METHODS: This prospective cohort study enrolled 222 in-patients administered one of the following opioid therapies for cancer pain as part of an opioid introduction or rotation strategy: tapentadol extended-release tablets, methadone tablets, hydromorphone controlled-release tablets, oxycodone controlled-release tablets, or transdermal fentanyl patches. The impact of A118G polymorphism on the difference in the Brief Pain Inventory-Short Form score on days three, seven, and 14 from baseline was compared among the groups. RESULTS: Overall, 81, 74, and 67 patients had the AA, AG, and GG genotypes, respectively, with an OPRM1 A118G G-allele variant frequency of 0.47. The reduction in the Brief Pain Inventory-Short Form score after opioid therapy initiation did not differ significantly among the patients with the three A118G genotypes treated with tapentadol (p = 0.84) or methadone (p = 0.97), whereas it was significantly smaller in G-allele carriers than that in AA homozygous patients treated with hydromorphone (p < 0.001), oxycodone (p = 0.031), or fentanyl (p < 0.001). CONCLUSION: Tapentadol and methadone may be more suitable than hydromorphone, oxycodone, and fentanyl for G-allele carriers due to their dual mechanism of action and low susceptibility to OPRM1 A118G polymorphism.

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.

Effects of S-ketamine added to patient-controlled analgesia on early postoperative pain and recovery in patients undergoing thoracoscopic lung surgery: A randomized double-blinded controlled trial.

STUDY OBJECTIVE: To investigate whether the addition of S-ketamine to patient-controlled hydromorphone analgesia decreases postoperative moderate-to-severe pain and improves the quality of recovery (QoR) in patients undergoing thoracoscopic lung surgery. DESIGN: Single-center prospective randomized double-blinded controlled trial. SETTING: Tertiary university hospital. PATIENTS: 242 patients undergoing thoracoscopic lung surgery. INTERVENTIONS: Patients were randomized to receive intravenous patient-controlled analgesia (IV-PCA) with hydromorphone alone or hydromorphone combined with S-ketamine (0.5 mg/kg/48 h, 1 mg/kg/48 h, or 2 mg/kg/48 h). MEASUREMENTS: Primary outcome was proportion of patients with moderate-to-severe pain. (numerical rating scale [NRS] pain scores ≥4 when coughing) within 2 days after surgery. Postoperative QoR scores and other prespecified outcomes were also recorded. MAIN RESULTS: Of 242 enrolled patients, 220 were included in the final analysis. The results demonstrated that the incidence of postoperative moderate-to-severe pain was significantly different between the hydromorphone group and combined S-ketamine group (absolute difference, 27.9%; 95% confidence interval [CI], 11.7% to 42.1%; P < 0.001). Patients who received S-ketamine had lower NRS pain scores at rest and when coughing on postoperative day 1 (POD1; median difference 1 and 1, P < 0.001) and postoperative day 2 (POD2; median difference 1 and 1, P < 0.001). The QoR-15 scores were higher in the combined S-ketamine group on POD1 (mean difference 6, P < 0.001) and POD2 (mean difference 6, P < 0.001) than in the hydromorphone group. A higher dose of S-ketamine was associated with deeper sedation. No differences were detected in the other safety outcomes. CONCLUSIONS: Addition of S-ketamine to IV-PCA hydromorphone significantly reduced the incidence of postoperative moderate-to-severe pain and improved the QoR in patients undergoing thoracoscopic lung surgery. TRIAL REGISTRATION: Chinese Clinical Trail Register (identifier: ChiCTR2200058890).

Evaluation of Thermal Antinociceptive Effects of Intramuscular Hydromorphone Hydrochloride in Great Horned Owls (Bubo virginianus).

Across the Americas, great horned owls (Bubo virginianus) are often presented to veterinarians for conditions requiring pain management. Although recent studies have evaluated opioid drugs in raptor species, information in Strigiformes is lacking. The objective of this study was to evaluate the analgesic effect and duration of action of hydromorphone hydrochloride, a full µ-opioid receptor agonist, in great horned owls. In a randomized, blinded, balanced crossover study, 6 adult birds (5 females and 1 male) received hydromorphone (0.3 and 0.6 mg/kg) or saline (0.9% NaCl) solution (0.03 mL/kg; control) in the left pectoral muscle, with a 7-day washout interval between treatments. Each bird was assigned an agitation-sedation score, and the thermal foot withdrawal threshold (TFWT) was measured at predetermined times before (t = 0 hours) and after treatment administration (t = 0.5, 1.5, 3, and 6 hours). Measurements of the TFWT were obtained with a test box equipped with a thermal perch, which delivered a gradually increasing temperature 40-62°C (104-143.6°F) to the right plantar surface of the owl's foot. Compared with controls, hydromorphone at 0.3 mg/kg dose resulted in significantly higher mean TFWT at 0.5 hours (P < 0.001), 1.5 hours (P = 0.003), and 3 hours (P = 0.005), whereas the 0.6 mg/kg dose resulted in significantly higher mean TFWT from 0.5 hours (P = 0.035) to 1.5 hours (P = 0.001). Both hydromorphone doses were associated with a significant change in the agitation-sedation score (P = 0.001), consistent with mild to moderate sedation. Two owls were observed tremoring after administration of the 0.6 mg/kg dose, which was not noted after the 0.5-hour timepoint; no other adverse effects were identified. This study offers scientific evidence to support the use of a µ-opioid agonist in great horned owls for pain management. Pharmacokinetics and other pharmacodynamic studies of other pain models evaluating hydromorphone and other opioid drugs in this species are still needed.

Prevalence of opioid-induced adverse events across opioids commonly used for analgesic treatment in Japan: a multicenter prospective longitudinal study.

PURPOSE: Although opioids have been shown to be effective for cancer pain, opioid-induced adverse events (AEs) are common. To date, little is known about the differences in risks of AEs by opioid type. This study was performed to compare the prevalence of AEs across opioids commonly used for analgesic treatment in Japan. METHODS: This study was conducted as a preplanned secondary analysis of a multicenter prospective longitudinal study of inpatients with cancer pain who received specialized palliative care for cancer pain relief. We assessed daily AEs until termination of follow-up. We rated the severity of AEs based on the Common Terminology Criteria for Adverse Events version 5.0. We computed adjusted odds ratios for each AE (constipation, nausea and vomiting, delirium, and drowsiness) with the following variables: opioid, age, sex, renal dysfunction, and primary cancer site. RESULTS: In total, 465 patients were analyzed. Based on the descriptive analysis, the top four most commonly used opioids were included in the analysis: oxycodone, hydromorphone, fentanyl, and tramadol. With respect to the prevalence of AEs among all analyzed patients, delirium (n = 25, 6.3%) was the most frequent, followed by drowsiness (n = 21, 5.3%), nausea and vomiting (n = 19, 4.8%), and constipation (n = 28, 4.6%). The multivariate logistic analysis showed that no single opioid was identified as a statistically significant independent predictor of any AE. CONCLUSION: There was no significant difference in the prevalence of AEs among oxycodone, fentanyl, hydromorphone, and tramadol, which are commonly used for analgesic treatment in Japan.

Dexamethasone and dexmedetomidine as adjuvants to ropivacaine do not prolong analgesia in wound infiltration for lumbar spinal fusion: a prospective randomized controlled study.

BACKGROUND AND OBJECTIVES: Local anesthetics (LAs) are widely used to infiltrate into surgical wounds for postoperative analgesia. Different adjuvants like dexamethasone and dexmedetomidine, when added to LA agents, could improve and prolong analgesia. The aim of this trial was to evaluate the analgesic efficacy and opioid-sparing properties of dexamethasone and dexmedetomidine when added to ropivacaine for wound infiltration in transforaminal lumbar interbody fusion (TLIF). METHODS: We conducted a controlled study among 68 adult patients undergoing TLIF, which was prospective, randomized and double-blind in nature. The participants were divided into four equal groups at random. Group R was given 150 mg of 1% ropivacaine (15 mL) and 15 mL of normal saline. Group R + DXM received 150 mg of 1% ropivacaine (15 mL) and 10 mg of dexamethasone (15 mL). Group R + DEX received 150 mg of 1% ropivacaine (15 mL) and 1 µg/kg of dexmedetomidine (15 mL). Lastly, group R + DXM + DEX was given 150 mg of 1% ropivacaine (15 mL), 10 mg of dexamethasone and 1 µg/kg of dexmedetomidine (15 mL). The primary focus was on the length of pain relief provided. Additionally, secondary evaluations included the amount of hydromorphone taken after surgery, the numerical rating scale and safety assessments within 48 h after the operation. RESULTS: Based on the p value (P > 0.05), there was no significant variance in the duration of pain relief or the total usage of hydromorphone after surgery across the four groups. Similarly, the numerical rating scale scores at rest and during activity at 6-, 12-, 24- and 48-h post-surgery for all four groups showed no difference (P > 0.05). However, the incidence of delayed anesthesia recovery was slightly higher in group R + DEX and group R + DXM + DEX when compared to group R or group R + DXM. Furthermore, there were no significant differences between the four groups in terms of vomiting, nausea, dizziness or delayed anesthesia recovery. CONCLUSION: For wound infiltration in TLIF, the addition of dexamethasone and dexmedetomidine to ropivacaine did not result in any clinically significant reduction in pain or opioid consumption and could prompt some side effects.

Retrospective Review of Intrathecal Hydromorphone Dose Range and Complications.

BACKGROUND: Optimal intrathecal dosing regimens for hydromorphone are not well established for analgesia after abdominal surgery. OBJECTIVES: We reviewed intrathecal hydromorphone doses and complications because dosing variability has been observed among anesthesiologists. We hypothesized that increasing doses of intrathecal hydromorphone would be associated with improved postoperative analgesia, but with increased rates of opioid-related adverse events. STUDY DESIGN: Retrospective analysis. SETTING: A high-volume academic referral center in the United States. METHODS: A retrospective study was conducted of adults undergoing abdominal surgery under general anesthesia supplemented preoperatively with intrathecal hydromorphone for postoperative analgesia from May 5, 2018, through May 31, 2021. Patients were categorized into 3 hydromorphone dosing groups: low-dose (50-100 µg), middle-dose (101-199 µg), and high-dose (200-300 µg). Multivariable logistic regression models were used to assess rates of severe postoperative pain, severe opioid-related adverse events, oversedation, and pruritus in the postanesthesia care unit (PACU) and within 24 hours after PACU discharge. RESULTS: Of 1,846 patients identified, 1,235 (66.9%) were in the low-dose group; 321 (17.3%), middle-dose group; and 290 (15.7%), high-dose group. Patients receiving the 2 higher doses had more extensive procedures. An unadjusted analysis showed differing rates of severe pain in the PACU by group: 306 (24.8%) in the low-dose, 73 (22.7%) middle-dose, and 45 (15.5%) in the high-dose group (P = 0.003); these differences, however, were no longer significant after an adjusted analysis (P = 0.34). Ten severe opioid-related events occurred; all were recognized in the PACU. Five events each occurred in the low-dose and high-dose groups versus none in the middle-dose group (P = 0.02). No other differences were identified with adjusted analyses. LIMITATIONS: Limitations of our study include its retrospective design and its conduct at a single center, along with the apparent, but difficult to characterize, treatment biases in hydromorphone dosing. CONCLUSIONS: No dose response was observed between intrathecal hydromorphone dose and postoperative analgesia, a finding that may reflect treatment bias. Higher rates of severe opioid-related events were detected for patients receiving high-dose hydromorphone in the PACU, but all other safety outcomes were similar between dosing regimens. KEY WORDS: Drug-related side effects, opioid analgesics, outcome assessment, postoperative pain, spinal injections.

Postoperative Catatonia After Fentanyl, Hydromorphone, and Ketamine Administration in a Patient Taking Sertraline: A Case Report.

Opioid-induced catatonia is underrecognized and poorly understood in the literature. An 81-year-old woman with chronic kidney disease stage III taking sertraline underwent surgery with general anesthesia, receiving fentanyl, hydromorphone, and ketamine. Postoperatively, she was unresponsive, rigid, and cataleptic with pinpoint pupils. Symptoms resolved with a naloxone infusion suggesting opioid-induced catatonia as the leading diagnosis. Differential diagnoses and etiologies discussed reveal a possible multifactorial catatonia mechanism involving opioids, ketamine, and serotonin. Anesthesiologists should consider these potential interactions when using opioids for management of vulnerable patients.

Association of Intraoperative Opioid Administration With Postoperative Pain and Opioid Use.

Importance: Opioids administered to treat postsurgical pain are a major contributor to the opioid crisis, leading to chronic use in a considerable proportion of patients. Initiatives promoting opioid-free or opioid-sparing modalities of perioperative pain management have led to reduced opioid administration in the operating room, but this reduction could have unforeseen detrimental effects in terms of postoperative pain outcomes, as the relationship between intraoperative opioid usage and later opioid requirements is not well understood. Objective: To characterize the association between intraoperative opioid usage and postoperative pain and opioid requirements. Design, Setting, and Participants: This retrospective cohort study evaluated electronic health record data from a quaternary care academic medical center (Massachusetts General Hospital) for adult patients who underwent noncardiac surgery with general anesthesia from April 2016 to March 2020. Patients who underwent cesarean surgery, received regional anesthesia, received opioids other than fentanyl or hydromorphone, were admitted to the intensive care unit, or who died intraoperatively were excluded. Statistical models were fitted on the propensity weighted data set to characterize the effect of intraoperative opioid exposures on primary and secondary outcomes. Data were analyzed from December 2021 to October 2022. Exposures: Intraoperative fentanyl and intraoperative hydromorphone average effect site concentration estimated using pharmacokinetic/pharmacodynamic models. Main Outcomes and Measures: The primary study outcomes were the maximal pain score during the postanesthesia care unit (PACU) stay and the cumulative opioid dose, quantified in morphine milligram equivalents (MME), administered during the PACU stay. Medium- and long-term outcomes associated with pain and opioid dependence were also evaluated. Results: The study cohort included a total of 61 249 individuals undergoing surgery (mean [SD] age, 55.44 [17.08] years; 32 778 [53.5%] female). Increased intraoperative fentanyl and intraoperative hydromorphone were both associated with reduced maximum pain scores in the PACU. Both exposures were also associated with a reduced probability and reduced total dosage of opioid administration in the PACU. In particular, increased fentanyl administration was associated with lower frequency of uncontrolled pain; a decrease in new chronic pain diagnoses reported at 3 months; fewer opioid prescriptions at 30, 90, and 180 days; and decreased new persistent opioid use, without significant increases in adverse effects. Conclusions and Relevance: Contrary to prevailing trends, reduced opioid administration during surgery may have the unintended outcome of increasing postoperative pain and opioid consumption. Conversely, improvements in long-term outcomes might be achieved by optimizing opioid administration during surgery.