Hydromorphone Research Articles

Efficacy of patient-controlled intravenous analgesia with hydromorphone hydrochloride plus flurbiprofen axetil after endoscopic sinus surgery

Objective: To evaluate the efficacy of patient-controlled intravenous analgesia (PCIA)with hydromorphone hydrochloride plusflurbiprofen axetil after endoscopic sinus surgery(ESS). Methods: One hundred patients of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, scheduled for ESS under total intraveous anesthesia with postoperative PCIA in Beijing Tongren Hospital from October 2015 to April 2016 were randomly divided into 3 groups according to the different formula of PCIA pumpin each group: Group A (hydromorphone hydrochloride 1 μg·kg(-1)·h(-1)+ flurbiprofen axetil 200 mg), Group B(hydromorphone hydrochloride 2 μg·kg(-1)·h(-1)), Group C( hydromorphone hydrochloride 1 μg·kg(-1)·h(-1)). The dosage of PCIA in each group was calculated for 50 h, and was diluted in 100 ml normal saline. All the pump was set up background infusion at a rate of 2 ml/h with a 2 ml bolus dose and a 15 min lock-time.Visual analogue scale (VAS) and Ramsay sedation scores at time points of postoperative 1, 4, 8, 12, 24, 48 h, the number of attempts to press bolus and rate of adverse effects within 48 h were recorded. The differences were compared among the groups. Results: VAS at postoperative 1, 4, 8, 12 h in Group A was (1.9±0.6), (1.8±0.6), (1.6±0.6), and (1.2±0.4) respectively, in Group B was (1.8±0.4), (1.7±0.7), (1.6±0.6), and (1.3±0.5) respectively, in Group C was (2.5±0.9), (1.7±0.7), (1.6±0.6), and (1.3±0.5) respectively. The difference among each group were statistically significant (F=8.661, 3.105, 4.903, 13.846, P<0.05). VAS in Group A was similar to that in Group B(P>0.05), but was lower than that in Group C(P<0.05). The number of attempts to press bolus within 48 h in group A was 1.4±1.0, which was less than in Group C(2.2±1.8 , P<0.05). Ramsay sedation score at postoperative 1, 4, 8 h in Group A was (2.4±0.6), (2.2±0.6), and (2.2±0.4) respectively, in Group B was (2.8±0.7), (2.6±0.7), and (2.4±0.6) respectively, in Group C was (2.3±0.6), (2.1±0.4), and (2.1±0.2) respectively. The difference among each group were statistically significant (F=5.660, 6.782, 7.141, P<0.05). Ramsay sedation score in group A was similar to that in Group C(P>0.05), but was lower than that in Group B(P<0.05). The total rate of adverse effects in Group A was 8.8%, which was similar to that in Group C (9.1%, χ(2)=0.001, P>0.05), but was significantly lower than that in Group B (42.5%, χ(2)=9.99, P<0.05). Conclusion: 1 μg·kg(-1)·h(-1) hydromorphone hydrochloride plus 200 mg flurbiprofen axetil is effective on PCIA for patients after ESS and can reduce the dosage of hydromorphone hydrochloride and the rate of adverse effects as well.

A randomized, double-blind study of hydromorphone hydrochloride extended-release tablets versus oxycodone hydrochloride extended-release tablets for cancer pain: efficacy and safety in Japanese cancer patients (EXHEAL: a Phase III study of EXtended-release HydromorphonE for cAncer pain reLief).

BackgroundIn Japan, there are limited options for switching opioid analgesics. Hydromorphone is an opioid analgesic that is routinely used instead of morphine for cancer pain; however, it is not yet available in Japan. The aim of this study was to assess the efficacy and safety of hydromorphone (DS-7113b) extended-release tablets in opioid-naïve patients with cancer pain not relieved by non-opioid analgesics.Subjects and methodsThis was a multicenter, randomized, double-blind, parallel-group trial. A double-dummy method was used for blinding. Each randomized subject received either hydromorphone extended-release tablets plus placebo oxycodone hydrochloride extended-release tablets 4 mg/day (n=88) or placebo hydromorphone extended-release tablets plus oxycodone hydrochloride extended-release tablets 10 mg/day (n=93) orally for 7 days (once-daily dosing for hydromorphone and twice-daily dosing for oxycodone). The doses were adjusted as necessary. Efficacy was evaluated by change in visual analog scale (VAS) score from baseline to completion of treatment.ResultsThe between-group difference in least squares mean changes in VAS score from baseline to completion or discontinuation of treatment was −0.4 mm (95% CI −5.9 to 5 mm) by analysis of covariance where the baseline VAS score was used as a covariate. The upper limit of the 95% CI was below 10 mm, which was predefined as the noninferiority limit. This verified the noninferiority of hydromorphone tablets relative to oxycodone tablets. The incidence of adverse events was 80.7% (71 of 88) in the hydromorphone group and 83.7% (77 of 93) in the oxycodone group. The most common adverse events were nausea, vomiting, somnolence, diarrhea, and constipation, most of which are commonly observed with opioid analgesics.ConclusionThe efficacy and safety of hydromorphone extended-release tablets were equivalent to those of the oxycodone extended-release formulation.

Hydromorphone

Hydromorphone

Effects of hydromorphone in prevention of shivering after spinal anesthesia

Eighty patients(American Society of AnesthesiologistsⅠ-Ⅱ)scheduled for elective unilateral inguinal hernia surgery with spinal anesthesia between January and June 2016 were randomized into two groups with 40 in each group. Patients were intravenously injected with normal saline (5 ml) in control group or hydromorphone 5 μg/kg (diluted to 5 ml) in intervention group after spinal anesthesia. Tympanic temperature and the incidence of shrivering were measured before and after spinal anesthesia at predetermined intervals. Side effects during surgery and the first 48 h after surgery were recorded. Rescue drug tramadol 0.5 mg/kg was given intravenously to patients with grade ≥2 shivering for more than 5 min duration. Tympanic temperature decreased significantly compared to the baseline from 20 min in control group and from 10 min in intervention group after spinal blocking(P 0.05). The incidence of shivering was significantly lower in intervention group [17.5%(7/40) ] than that in control group [47.5%(19/40), χ2=8.205, P=0.004]. The incidence of nausea and vomiting was 5.0%(2/40)in intervention group and 0.0% (0/40) in control group (χ2=2.051, P=0.494). The incidence of sedation was not significantly different between control group [0.0%(0/40)] and intervention group[10.0%(4/10) , χ2=4.211, P=0.116]. The use of rescue tramadol was more frequently in control group [32.5%(13/40)] than that in intervention group [7.5%(3/40), χ2=7.812, P=0.01]. The results indicate that intravenous hydromorphone can significantly attenuate the incidence of shivering after spinal anesthesia for inguinal herniorrhaphy repair surgery with minimum side effects. Key words: Hydromorphone; Shivering; Anesthesia, spinal; Hernia, inguinal

Hydromorphone withdrawal

Hydromorphone withdrawal

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Hydromorphone

Observation of clinical effect and adverse reaction of hydromorphone for continuous epidural analgesia after cesarean section

Objective To learn the clinical effect and adverse reaction of hydromorphone for continuous epidural analgesia after cesarean section, and to provide effective anesthesia method for clinical. Methods 116 cases of cesarean section were randomly divided into observation group(65 cases) and control group(51 cases), continuous epidural analgesia was used in the two groups after operation.Among them, hydromorphone + ropivacaine was used for the observation group, morphine + ropivacaine was used for the control group.The analgesic effect and sedation degree of the two groups were evaluated. The adverse drug reactions were observed, and satisfaction of the patients after the operation was investigated. Results 6, 9, 24 hours after operation, the VAS pain scores of the observation group were lower than those of the control group, the differences were statistically significant(t=3.236, 4.970, 2.547, all P 0.05). The difference of postoperative first exhaust time between the two groups was not statistically significant(t=0.730, P>0.05). The satisfaction degree of the observation group was significantly higher than that of the control group, the difference was statistically significant(t=2.301, P 0.05). Conclusion For continuous epidural analgesia after cesarean section, hydromorphone can effectively relieve the pain after operation, the safety of the process is high, and it has good clinical application value. Key words: Cesarean Section; Analgesia, Epidural; Hydromorphone; Morphine; Ropivacaine

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Hydromorphone abuse

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Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats

ObjectiveTo determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. Study designRandomized crossover study. AnimalsSix healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. MethodsMorphine sulfate (0.2 mg kg−1 IV or 0.5 mg kg−1 buccal), methadone hydrochloride (0.3 mg kg−1 IV or 0.75 mg kg−1 buccal), hydromorphone hydrochloride (0.1 mg kg−1 IV or 0.25 mg kg−1 buccal) or oxymorphone hydrochloride (0.1 mg kg−1 IV or 0.25 mg kg−1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. ResultsAdministration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. Conclusion and clinical relevanceAt the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients.

The conversion ratio from intravenous (IV) hydromorphone to oral (PO) opioids in patients with cancer.

197 Background: Inpatients with cancer frequently undergo conversions from IV to PO hydromorphone (HM) or opioid rotation (OR) from IV HM to another PO opioid prior to discharge. Currently used conversion ratios (CR) between IV and PO HM range from 2-5 and opioid rotation ratios (ORR) between IV HM and oral morphine equivalent daily dose (MEDD) range from 10-20. This large variation in ratios may lead to uncontrolled pain or overdosing. Our aim was to determine the accurate CR from IV to PO HM and ORR from IV HM to PO morphine and oxycodone (measured as MEDD). Methods: We reviewed records of 4745 consecutive inpatient palliative care consults in our institute during 2010-14 for patients who underwent conversion from IV to PO HM or OR from IV HM to PO morphine or oxycodone. Patient characteristics, symptoms and opioid doses were determined in patients successfully discharged on oral opioids without readmission within 1 week. Linear regression analysis was used to estimate the CR or ORR between the 24 hour IV HM mg dose prior to conversion to PO and the oral opioid mg dose used in the 24 hours prior to discharge. Results: Among 394 eligible patients on IV HM, 147 underwent conversion to PO HM and 247 underwent OR to oral morphine (163) or oxycodone (84). Mean age was 54 years, 39% were male, and 95% had advanced cancer. Median time between conversion to PO and discharge was 2 days. In 147 patients the median CR (IQR) from IV to PO HM was 2.5 (2.1-2.7) and correlation of IV to PO dose of HM was .95 (P &lt; .0001). The median CR was 2.5 in patients receiving &lt; 30mg of IV HM/day and 2.1 in patients receiving ≥ 30mg of HM/day (P = .004). In 247 patients the median ORR (IQR) from IV HM to MEDD was 11.5 (10-13) and correlation of IV HM to MEDD was .93 (P &lt; .0001). The median ORR was 11.5 in patients receiving &lt; 30mg of IV HM/day and 9.9 in patients receiving ≥ 30mg of HM/day (P = .0004). ORR from IV HM to MEDDs obtained from morphine (11) and oxycodone (12.1) were significantly different (P = .0023). The CR and ORR were not significantly impacted by other variables. Conclusions: The median CR from IV to PO HM is 2.5 and ORR from IV HM to MEDD is 11.5. This implies that 1 mg IV HM is equivalent to 2.5 mg PO HM and 11.5 mg MEDD. HM may cause hyperalgesia at doses ≥ 30 mg/day and thereby requires a lower ORR to other opioids.

Hydromorphone

Hydromorphone

Prescription Opioids. VI. Metabolism and Excretion of Hydromorphone in Urine Following Controlled Single-Dose Administration.

Hydromorphone (HM), a prescription opioid and metabolite of morphine and hydrocodone, has been included in proposed revisions to the Mandatory Guidelines for Federal Workplace Drug Testing Programs. This study characterized the time course of HM in hydrolyzed and non-hydrolyzed urine specimens. Twelve healthy subjects were administered a single 8 mg controlled-release HM dose, followed by periodic collection of pooled urine specimens for 54 h following administration. Analysis of total and free HM was conducted by liquid chromatography tandem mass spectrometry at a 50 ng/mL limit of quantitation. Detection periods were determined over a range of thresholds from 50 to 2,000 ng/mL. HM was detected in 85.3% and 47.6% of hydrolyzed and non-hydrolyzed post-dose specimens, respectively. Initial detection of total HM was frequently observed in the first 4-6 h following dosing. The period of detection at the 50 ng/mL threshold averaged 52.3 h for total HM and 38.0 h for free HM. These data support that HM detection is optimized by using low thresholds (50-100 ng/mL) and including conjugated HM in the analysis.

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Hydromorphone Compared With Diacetylmorphine for Long-term Opioid Dependence

Diacetylmorphine hydrochloride (the active ingredient in heroin), delivered under supervision, is effective for the treatment of severe opioid use disorder. However, owing to political and regulatory barriers, it is not available in many settings around the world, which limits the options for many long-term street opioid injectors not attracted into or retained in available treatments. To test if injectable hydromorphone hydrochloride is noninferior to injectable diacetylmorphine in reducing illicit heroin use for chronic injection opioid users after 6 months of intervention. The Study to Assess Longer-term Opioid Medication Effectiveness (SALOME) was a phase 3, double-blind, noninferiority trial. The study randomized 202 long-term street opioid injectors in Vancouver, British Columbia, Canada. Eligible participants were recruited between December 19, 2011, and December 18, 2013. Both intent-to-treat (ITT) and per-protocol (PP) analyses were conducted. Participants were randomly assigned to receive injectable diacetylmorphine or hydromorphone (up to 3 times daily) for 6 months under supervision. Primary and coprimary efficacy outcomes were self-reported days of street heroin use (primary), days of any street-acquired opioids in the prior 30 days (noninferiority margin, 4 days), and the proportion of urinalyses positive for street heroin markers (margin, 10% of the observed rate in the diacetylmorphine group). The mean differences between diacetylmorphine and hydromorphone for the ITT and PP analyses were reported. The study included 202 participants; 100 randomized to receive hydromorphone and 102 to diacetylmorphine. Their mean (SD) age was 44.33 (9.63) years, and 30.7% (62 of 202) were women. Noninferiority of hydromorphone was confirmed in the PP analysis (-1.44; 90% CI, -3.22 to 0.27) for street heroin use, although the margin of 4 days was not excluded in the ITT analysis (-2.34; 90% CI, -4.14 to -0.52). Noninferiority was confirmed for any street opioids in the ITT analysis (-0.85; 90% CI, -2.97 to 1.25) and the PP analysis (-0.15; 90% CI, -2.09 to 1.76), as well as for the urinalyses (0.09; 90% CI, -0.02 to 0.19 for the ITT analysis and 0.13; 90% CI, 0.02-0.24 for the PP analysis). There were 29 SAEs considered to have some relationship with the injection medication, 5 in the hydromorphone group and 24 in the diacetylmorphine group (rate ratio, 0.21; 95% CI, 0.06-0.69). Seizures and overdoses accounted for 25 of the 29 related SAEs. This study provides evidence to suggest noninferiority of injectable hydromorphone relative to diacetylmorphine for long-term opioid dependence. In jurisdictions where diacetylmorphine is currently not available or for patients in whom it is contraindicated or unsuccessful, hydromorphone could be offered as an alternative. clinicaltrials.gov Identifier: NCT01447212.

Hydromorphone

Hydromorphone