Relative analgesic potencies of morphine and hydromorphone in postoperative pain. Patient-controlled analgesia: a comparison of intravenous versus subcutaneous hydromorphone. Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain. Epidural hydromorphone: a double-blind comparison with intramuscular hydromorphone for postcesarean section analgesia. Intravenous versus epidural administration of hydromorphone. Effects on analgesia and recovery after radical retropubic prostatectomy. Spinal narcotics for postoperative analgesia in total joint arthroplasty. A prospective study. A multidimensional comparison of morphine and hydromorphone patient-controlled analgesia. Morphine and hydromorphone epidural analgesia. A prospective, randomized comparison. Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation. [Postoperative pain therapy with hydromorphone and metamizole. A prospective randomized study in intravenous patient-controlled analgesia (PCA)]. Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer pain. Postoperative analgesia with hydromorphone and meperidine: a double-blind comparison. Epidural morphine vs hydromorphone in post-caesarean section patients. Safety and efficacy of hydromorphone as an analgesic alternative to morphine in acute pain: a randomized clinical trial. Clinical analgesic assay of repeated and single doses of heroin and hydromorphone. Comparison of hydromorphone and meperidine for ureteral colic. Hydromorphone patient-controlled analgesia (PCA) after coronary artery bypass surgery. Comparison of epidural morphine, hydromorphone and fentanyl for postoperative pain control in children undergoing orthopaedic surgery. A randomized, placebo-controlled study of outpatient premedication for bone marrow biopsy in adults with lymphoma. Patient-controlled analgesia for mucositis pain in children: a three-period crossover study comparing morphine and hydromorphone. Epidural hydromorphone with and without epinephrine for post-operative analgesia after cesarean delivery. Dental evaluation of hydromorphone (Dilaudid) for oral and maxillo-facial surgery. Epidural patient-controlled analgesia: influence of bupivacaine and hydromorphone basal infusion on pain control after cesarean delivery. Epidural patient-controlled analgesia: an alternative to intravenous patient-controlled analgesia for pain relief after cesarean delivery. Effect of pre-emptive hydromorphone administration on postoperative pain relief--a randomized controlled trial. Epidural hydromorphone for postcesarean analgesia. Patient-controlled subcutaneous hydromorphone versus continuous subcutaneous infusion for the treatment of cancer pain. Continuous subcutaneous infusion of morphine vs. hydromorphone: a controlled trial. ORAL HYDROMORPHONE IN TRAUMA. Comparison of hydromorphone continuous subcutaneous infusion and basal rate subcutaneous infusion plus PCA in cancer pain: a pilot study. Comparative efficacy of oral extended-release hydromorphone and immediate-release hydromorphone in patients with persistent moderate to severe pain: two randomized controlled trials. A comparison of oral transmucosal fentanyl citrate and oral hydromorphone for inpatient pediatric burn wound care analgesia. Comparative clinical efficacy and safety of immediate release and controlled release hydromorphone for chronic severe cancer pain. Pain outcomes after thoracotomy: lumbar epidural hydromorphone versus intrapleural bupivacaine. A randomized, double-blind, double-dummy, crossover trial comparing the safety and efficacy of oral sustained-release hydromorphone with immediate-release hydromorphone in patients with cancer pain. Canadian Palliative Care Clinical Trials Group.
Because of discrepancies in the estimates of the relative analgesic potencies of hydromorphone and morphine, the drugs were compared in two four-point, double-blind bioassays. In the first study, hydromorphone, 1 and 2 mg, was compared with morphine, 5 and 10 mg, in 31 postoperative patients; in the second, hydromorphone, 0.5 and 1 mg, was compared with morphine, 5 and 10 mg, in 112 postoperative patients. Subjective responses to nurse-observer questions were used to quantitate analgesia for postoperative pain. Hydromorphone is more potent than commonly believed: approximately 0.9 to 1.2 mg is equianalgesic with 10 mg of morphine, with a similar incidence of side effects. nan To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned. nan It remains unclear whether epidural administration of hydromorphone results in spinal analgesia or clinical benefit when compared with intravenous administration. Therefore, we undertook this study to determine whether epidural administration of hydromorphone resulted in decreased opioid requirement, improved analgesia, reduced side effects, more rapid return of gastrointestinal function, or shorter duration of hospital stay than intravenous administration.
                Sixteen patients undergoing radical retropubic prostatectomy were randomized in a double-blind manner to receive either intravenous or epidural hydromorphone via patient-controlled analgesia (PCA) for postoperative analgesia. All patients underwent a standardized combined epidural and general anesthetic and all received ketorolac for 72 h postoperatively. To decrease variability, patients were cared for according to a standardized protocol and were deemed ready for discharge according to prospectively defined criteria.
                Patients in the intravenous PCA group required approximately twice as much opioid than the epidural PCA group (P < 0.008), but there were no differences between groups in pain scores or patient satisfaction. Epidural administration resulted in a greater incidence of pruritus (P = 0.02). Gastrointestinal function recovered quickly in all patients with little variation, and there were no differences between groups. All patients were deemed ready for discharge by the third postoperative day, and removal of surgical drains was the last discharge criterion reached in all patients.
                Our results indicate that epidural administration of hydromorphone results in spinally mediated analgesia. However, epidural administration did not provide significant benefits in terms of postoperative analgesia, recovery of gastrointestinal function, or duration of hospitalization. Furthermore, we suggest that radical retropubic prostatectomy no longer be used as a model to assess the effects of analgesic technique on postoperative recovery, because control of discharge criteria revealed that hospital discharge was primarily dependent on removal of surgical drains. Sixty patients who were scheduled to have an elective total hip or knee arthroplasty were randomly assigned to one of three groups of twenty patients each before operation with spinal anesthesia. A double-blind technique was used throughout the study. The patients in Group I (control group) received hyperbaric 1 per cent tetracaine with epinephrine as the subarachnoid spinal anesthetic; the patients in Group II (morphine group), hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Duramorph (morphine sulphate), 0.5 milligram; and those in Group III (Dilaudid group), hyperbaric 1 per cent tetracaine with epinephrine and a single subarachnoid dose of Dilaudid (hydromorphone hydrochloride), 0.002 milligram per kilogram of body weight. During the first twenty-four hours after the operation, the patients in Group II and Group III had significantly less pain compared with those in Group I. This was shown by the use of a visual linear-analog pain scale (p less than 0.05), the patients' ratings of the quality of relief of pain (p less than 0.02), and comparative measurements of the pain-altering medications that were used (p less than 0.05). The patients in Group II and Group III did not have any more complications or side effects than those in Group I. There was no significant difference in the quality and duration of analgesia between Group II and Group III. Although patient-controlled analgesia (PCA) pumps have been in use for more than a decade, the optimal PCA analgesic has yet to be identified. Many drugs are used; however, morphine remains the "gold standard" of opioid analgesics worldwide. The present study evaluated morphine and hydromorphone (Dilaudid) PCA with respect to analgesic efficacy, side effects, mood, and cognitive function. Sixty-one opioid naive patients undergoing lower abdominal surgery participated in the double-blind protocol. Verbal rating scores, use of medication, and side effects for the two medications were recorded. Cognitive functioning was assessed by computation of Digit Symbol and Trails Making B Tests. Self-reported affective state (mood) was measured by Profile of Mood States (POMS) inventory. Both medications provided adequate analgesia without a difference in side effects. Cognitive performance was poorer in the hydromorphone group (P < 0.05). Patients receiving hydromorphone reported less anger/hostility (P < 0.01) and generally better mood elevations on the other subscales than those receiving morphine. A similar incidence of side effects and dose medication can be anticipated with morphine and hydromorphone. When considering cognitive effects, morphine had less adverse consequences, while hydromorphone appeared to result in improved mood. We conclude that hydromorphone may provide a suitable alternative to morphine. Because evidence from uncontrolled, unblinded studies suggested fewer side effects from epidural hydromorphone than from epidural morphine, we employed a randomized, blinded study design to compare the side effects of lumbar epidural morphine and hydromorphone in 55 adult, non-obstetric patients undergoing major surgical procedures. A bolus dose of epidural study drug was given at least 1 h prior to the conclusion of surgery, followed by a continuous infusion of the same drug for two postoperative days. Infusions were titrated to patient comfort. Visual analog scale (VAS) pain scores, VAS sedation scores, and subjective ratings of nausea and pruritus were assessed twice daily. The two treatments provided equivalent analgesia. Sedation scores and prevalence of nausea did not differ significantly between groups. Prevalence of pruritus, however, differed significantly on postoperative day 1, with moderate to severe pruritus reported by 44.4% of patients in the morphine group versus 11.5% in the hydromorphone group (P < .01). On post-operative day 2, reports of pruritus by patients receiving morphine remained higher than those among the hydromorphone-treated subjects, although this difference was no longer statistically significant (32% vs. 16.7%, P = .18). We conclude that lumbar epidural morphine and hydromorphone afford comparable analgesia, but the occurrence of moderate to severe pruritus on the first postoperative day is reduced by the use of hydromorphone. A total of 119 bone marrow transplant patients suffering from oral mucositis pain were enrolled in a randomized, double-blind, parallel-group trial comparing the efficacy of patient-controlled analgesia with morphine, hydromorphone and sufentanil. Patient ratings of pain and side-effects on visual analog scales were gathered daily from the start of patient-controlled analgesia (PCA) therapy until the discontinuation of opioid treatment either because of resolution of oral mucositis pain, intolerable side-effects, inadequate pain control, or complications related to transplantation. Of the 119 enrolled subjects, 100 met the evaluable criteria of developing oral mucositis and remaining on the study for at least 2 days. Multivariate analysis of the outcome measures indicated that the analgesia achieved in all three opioid groups was nearly equivalent, while measures of side-effects, especially for the combination of sedation, sleep and mood disturbances, were statistically lower in the morphine group than in hydromorphone or sufentanil groups. Patients in the hydromorphone group exhibited the most variability in pain control. Event analysis also indicated significant differences in time to treatment failure between the three groups, with the morphine arm exhibiting clear superiority. The proportion of patients discontinued because of inadequate pain relief was much higher in the sufentanil group (7/36) as compared to the hydromorphone (0/34) or the morphine group (1/30). The daily opioid consumption pattern showed a continual dose escalation during the first week of therapy for all groups, coincident with worsening mucositis. Morphine consumption reached a plateau by day 5, whereas hydromorphone and sufentanil consumption continued to rise until days 7 and 9, respectively. Sufentanil dose requirement increased by approximately 10-fold compared to morphine and hydromorphone, whose requirements increased only 5-fold, suggesting the possibility of development of acute pharmacological tolerance in some patients with this phenylpiperidine opioid. This study provides support for the recommendation that morphine is the opioid of first choice when patient-controlled analgesia is employed for the treatment of severe oropharyngeal pain in bone marrow transplantation (BMT) patients. Most potent opioid analgesics available in Germany have been investigated for use in postoperative patient-controlled analgesia (PCA). To conclude an older comparative series, it was the aim of the present study to define analgesic potency, side effects and patient acceptance of hydromorphone and its interaction with the non-opioid analgesic metamizole. A total of 120 patients recovering from elective abdominal or orthopaedic surgery, performed under standardised general anaesthesia, were randomised into 3 double-blind treatment groups to receive intravenous PCA demand doses of hydromorphone 283 micrograms (low dose, LD), 566 micrograms (high dose, HD) or a combination of hydromorphone 283 micrograms and metamizole 50 mg (low dose hydromorphone + metamizole, LM). Demand-independent low-dose background infusions were added to deliver hydromorphone at 67.9 micrograms/h in all groups, with additional metamizole at 12 mg/h in group LM. Lockout times were set to 2 min. After an average observation time of 24.5 +/- 2.6 h (mean, SD) since start of PCA, cumulative PCA hydromorphone doses in groups LD, HD and LM were 7.8 +/- 3.3, 12.1 +/- 4.8 and 7.5 +/- 2.0 mg, respectively, with the well known large inter-individual variability in all groups. Although hydromorphone consumption was significantly higher in group HD, self-reported pain intensities (VAS, retrospective pain scores) were quite comparable between the groups. Low dose, PCA bolus-linked metamizole did not significantly reduce hydromorphone consumption nor improve patient acceptance. Side-effects were typical for potent postoperative opioids, but never required special treatment; haemodynamic or respiratory complications were not observed in any patient. It can be concluded by comparison with other PCA opioid investigations performed under the same study protocol that hydromorphone is about 3-4 times as potent an analgesic as morphine under the conditions of intravenous postoperative PCA. Due to a favourable patient acceptance, hydromorphone can be recommended as a suitable alternative to other opioids for the treatment of postoperative pain. The use of oxycodone to treat chronic cancer pain has been hampered by its short elimination half-life, which necessitates administration every 4 hours. This study compared the clinical efficacy and safety of a novel oxycodone formulation with that of hydromorphone in the treatment of cancer pain.
                In a double-blind crossover study, 44 patients with stable cancer pain were randomized to controlled-release oxycodone or controlled-release hydromorphone, each given every 12 hours for 7 days. Pain intensity, nausea, and sedation were assessed by patients four times daily, and breakthrough analgesia was recorded.
                Thirty-one patients completed the study (18 women, 13 men; mean age, 56 +/- 3 years) and received a final controlled-release oxycodone dose of 124 +/- 22 mg per day and a final controlled-release hydromorphone dose of 30 +/- 6 mg per day. There were no significant differences between treatments in overall Visual Analogue Scale (VAS) pain intensity (VAS 28 +/- 4 mm vs. 31 +/- 4 mm), categorical pain intensity (1.4 +/- 0.1 vs. 1.5 +/- 0.1), daily rescue analgesic consumption (1.4 +/- 0.3 vs. 1.6 +/- 0.3), sedation scores (24 +/- 4 mm vs. 18 +/- 3 mm), nausea scores (15 +/- 3 mm vs. 13 +/- 3 mm), or patient preference. Two patients experienced hallucinations on controlled-release hydromorphone, but none did while receiving controlled-release oxycodone.
                Controlled-release oxycodone demonstrated excellent pharmacodynamic characteristics, analgesic efficacy, and safety as compared with controlled-release hydromorphone and represents an important new therapeutic option for cancer pain management. nan The purpose of this randomized controlled double blind study was to compare the efficacy of pain relief and the side effects of epidural hydromorphone and morphine in post-Caesarean patients.
                In all patients, epidural anaesthesia was induced using carbonated lidocaine 2% with 1:200,000 epinephrine and 50 micrograms fentanyl, given in incremental doses. Patients in Group 1 (n = 24) received 0.6 mg hydromorphone and patients in Group 2 (n = 22) received 3 mg morphine after delivery of the infant. Pain, pruritus and nausea were measured using a visual analog scale (at times: baseline, on admission to the recovery room, 3, 6, 12, 18 and 24 hr postoperatively), by the number of requests for additional medications and by an overall satisfaction score.
                There was no difference between the groups in pain relief of in the incidence and severity of side effects. Pruritus was more pronounced within the first six hours in Group 1 and at 18 hr in Group 2.
                Hydromorphone provides no clinical benefit over epidural morphine for post operative analgesia following Caesarean section. We compare a standard weight-based dose of intravenous hydromorphone (Dilaudid) to a standard weight-based dose of intravenous morphine in adults presenting to the ED with acute severe pain.
                This was a prospective, randomized, double-blind, clinical trial conducted in an academic medical center. Of the 198 adult patients presenting to the ED with acute severe pain who were randomized to receive either intravenous hydromorphone at 0.015 mg/kg or intravenous morphine at 0.1 mg/kg, 191 patients had sufficient data for analysis. The main outcome measure was the difference between the 2 groups in pain reduction at 30 minutes as measured on a validated numeric rating scale. Adverse effects, pain reduction at 5 minutes and 2 hours postbaseline, and additional analgesics and antiemetics were tracked as secondary outcome measures.
                The mean change of pain from baseline to 30 minutes postbaseline in patients allocated to intravenous hydromorphone was -5.5 numeric rating scale units versus -4.1 in patients allocated to intravenous morphine (difference -1.3; 95% confidence interval -2.2 to -0.5). Adverse effects were similar in both groups, with the exception of pruritus, which did not occur in patients receiving hydromorphone (0% versus 6% [difference -6%; 95% confidence interval -11% to -1%]). No patient required naloxone.
                For the treatment of acute, severe pain in the emergency department, intravenous hydromorphone at 0.015 mg/kg represents a feasible alternative to intravenous morphine at 0.1 mg/kg. A direct comparison of the analgesic activities of heroin and hydromorphone was carried out in cancer patients with postsurgical pain. Intramuscular doses of 5 and 10 mg of heroin were compared with 1 and 2 mg of hydromorphone in a randomized, double-blind, 4-point parallel group assay. Design innovations in the study provided that about half the patients would receive prior repeated doses of the same drug as the test medication, and half would receive the alternate medication. Both test drugs were found to be potent, relatively short acting analgesics with similar profiles of action. Hydromorphone was about 5 times as potent as heroin on a milligram basis. The comparison of those patients who had repeated doses of the same treatment prior to the test dose and those who had repeated doses of the alternate drug demonstrated no significant effect on the relative potency estimates. Side effect occurrence was similar for both drugs, with sleepiness the most prominent effect. The study supports the view that hydromorphone and heroin produce similar clinical effects, and that either drug may adequately substitute for the other. Covariate analysis indicated that time since last analgesic was positively related to analgesia, and amount of prior opioid had a negative relationship. To a lesser extent, increase in patient age was associated with an increase in analgesic scores. Taking these covariates into account served to increase the sensitivity of the analysis. To compare the efficacies of meperidine and hydromorphone in the treatment for ureteral colic in the emergency department (ED).
                A prospective, double-blind, randomized clinical trial was conducted over six months at a tertiary referral center with 93,000 annual ED visits. Seventy-three patients completed the study. The patients received either 1 mg of hydromorphone or 50 mg of meperidine IV at t = 0. Pain intensity was determined using a 10-cm visual analog scale at t = 0, 15, 30, 60, and 120 minutes. A second dose of the study drug could be given between t = 15 and t = 120 minutes when the clinician believed the initial dose was ineffective. Patients requiring more than one additional dose of analgesia were treated as nonresponders and were removed from the study.
                Thirty-six patients received hydromorphone and 37 received meperidine. The initial pain intensities (hydromorphone group = 8.4 +/- 1.5; meperidine group = 8.5 +/- 2.1), age distributions, sex distributions, and side effects of the two groups were comparable. Pain relief was better (p < 0.05) with hydromorphone at t = 15, 30, 60, and 120 minutes. The hydromorphone group required rescue analgesia less often (31% vs 68%, p < 0.01), had fewer IV pyelographies (IVPs) (28% vs 54%, p < 0.05), and had a lower proportion of hospital admissions (25% vs 49%, p = 0.08).
                For the fixed doses used in this study, the adult ureteral colic patients receiving hydromorphone achieved more pain relief, required less rescue medication, underwent fewer IVPs, and avoided hospital admission more frequently than did those receiving meperidine. We conducted a study to compare the effectiveness of patient-controlled analgesia (PCA) technique to conventional analgesic therapy (CAT) after coronary artery bypass graft (CABG). The PCA group received hydromorphone 0.1 mg.hr-1 basal infusion and bolus doses of 0.2 mg Q 5 min (maximum 1.2 mg.hr-1) while the CAT group received morphine 2.5 mg iv Q 30 min prn until extubation followed by prn meperidine 1 mg.kg-1 im Q 4 hr or acetaminophen 325 mg with codeine 30 mg po (1 or 2 tablets) when oral intake was possible. The degree of pain was assessed using a Visual Analogue Scale (VAS) starting after extubation and every 6-8 hr for the next 60 hr. Holter monitoring was initiated one hour after patient arrival in the Intensive Care Unit (ICU) and continued for 72 hr. Other measured variables were pulmonary function, sedation, side effects and total opioid requirements. Results show that the day-to-day VAS pain score decreased in the PCA group (P < 0.001) while it remained unchanged in CAT patients. The PCA patients had lower VAS pain scores at extubation (P < 0.05). During the third postoperative day, the PCA group had a lower VAS pain score, a lower incidence of severe pain defined as a score > 5 on the VAS scale, and a reduced incidence of myocardial ischaemia (P < 0.01). However, there was no difference in the duration, severity, area under the curve (AUC), or heart rate during ischaemic events. Postoperative pulmonary function was abnormal in both groups (NS) with minimal recovery by the fourth day.(ABSTRACT TRUNCATED AT 250 WORDS) The safety and side-effects profile of epidural administration of a hydrophilic (morphine), highly lipophilic (fentanyl) and a drug with intermediate hydrophilic and lipophilic activity (hydromorphone) were compared in 90 children undergoing orthopaedic procedures. Ninety patients were randomly assigned (30 in each group) to receive epidural morphine, hydromorphone, or fentanyl for postoperative analgesia. Respiratory effects, nausea, somnolence, urinary retention, pruritus and visual pain scales were evaluated and compared during a 30-h period following surgery. In the morphine group, 25% showed respiratory depression with oxygen saturation below 90% but there was no incidence of respiratory depression in the fentanyl or hydromorphone groups. Somnolence was prominent in some of the patients in all the groups, but was more prolonged in the morphine group. Statistically, there was no significant difference in nausea between the groups, but pruritus was more severe and frequent in the morphine group. The incidence of urinary retention in the morphine group was higher compared with the fentanyl and hydromorphone groups. In conclusion, epidural hydromorphone, demonstrating less side-effects, is preferable to morphine and fentanyl for epidural analgesia in children. The outpatient bone marrow biopsy and aspiration (BMBA) procedure performed with local anesthetic is often poorly tolerated in adults. This prospective, randomized, placebo-controlled, double-blind trial was designed to determine whether oral (p.o.) lorazepam and hydromorphone reduces pain and anxiety during BMBA. Eligible patients had lymphoma, had no prior BMBA, and were > or = 18 years old. Since patients had bilateral BMBA, each served as their own control. Patients were stratified by anxiety level using the Spielberger Trait Anxiety Scale and randomized to: A) placebo for the first BMBA and 2 mg lorazepam and 2 mg hydromorphone p.o. for the contralateral BMBA, or B) placebo for both BMBAS. Changes in pain and anxiety experienced between the first and second BMBA were measured by the Visual Analogue Scale (VAS) and the Spielberger State Anxiety Scale at the time of the BMBA and 24 hours later. Twenty-seven patients were enrolled and 25 were evaluable; there were 17 males and eight females. The median age was 57 years (range, 28-79 years). Overall, BMBA was reported as painful in both arms, with a median VAS pain score after the second BMBA of 3.9 (scale, 0-10) for arm A and 5.8 for arm B (P = 0.21). There was no difference in the change in pain, anxiety, or recalled anxiety between treatment arms (all P values > 0.05). The difference in the change in recalled pain was of borderline significance (P = 0.07) and consistent with benzodiazepine-induced anterograde amnesia. (1) To test the safety and efficacy of a clinical protocol for administering opioid by using patient-controlled analgesia (PCA) for the management of mucositis pain in children after bone marrow transplantation, (2) to compare the efficacy, side-effect profile, and potency ratio of morphine with those of hydromorphone by using PCA as the method of opioid administration, and (3) to obtain pharmacokinetic data on hydromorphone and morphine in this population of children.
                In this double-blind, three-period crossover study, patients were randomly assigned to receive either morphine (group 1) or hydromorphone (group 2) initially by means of PCA on days 1, 2, and 3 (period 1), to be followed on days 4, 5, and 6 (period 2) with the alternative opioid, followed by the opioid used at the commencement of the study on days 7, 8, and 9 (period 3). A clinical protocol for calculating the PCA commencement opioid dose and subsequent opioid-dose escalation was tested by measures of safety and efficacy. Measures of pain intensity and opioid side effects were made during the three periods. On the last study day (day 10), patients received a continuous infusion of opioid derived from the previous 24-hour PCA opioid requirement, and blood specimens were collected and stored for subsequent opioid analysis.
                Ten patients were enrolled in this study. Rapid escalation in opioid requirement commonly occurred at the commencement of PCA, followed by a variable plateau phase and then deescalation of opioid requirement after mucositis resolution. The measures demonstrated the safety and efficacy of the clinical protocol. In the concentrations used, there was no statistical difference between the mean daily pain, sedation, nausea and vomiting, and pruritus scores for both opioids (Friedman test). The analysis of variance of the log-total opioid doses per patient during periods 1, 2, and 3 indicated that patients used 27% more hydromorphone than expected from its presumed 7:1 ratio relative to morphine potency used in the PCA infusions. The mean plasma hydromorphone concentration was 4.7 ng/ml (range, 1.9 to 8.9 ng/ml), and the mean clearance was 51.7 ml/min per kilogram of body weight (range, 28.6 to 98.2 ml/min per kilogram). The mean plasma morphine, morphine-6-glucuronide, and morphine-3-glucuronide concentrations were 40.0 ng/ml (range, 15 to 62.5), 168.2 ng/ml (range, 54.4 to 231.9), and 391.0 ng/ml (range, 149.4 to 921.7), respectively. The mean morphine clearance was 34.3 ml/min per kilogram of body weight (range, 19.3 to 58.3). The mean molar ratios of morphine-6-glucuronide/morphine, morphine-3-glucoronide/morphine, and morphine-3-glucuronide/morphine-6-glucuronide were 2.48 (range, 1.4 to 3.3), 5.82 (range, 3.4 to 9.1), and 2.46 (range, 1.1 to 3.3), respectively.
                The safety and efficacy of a clinical protocol for the administration of opioids by means of PCA for mucositis pain after bone marrow transplantation was demonstrated. In this small study, hydromorphone was not superior to morphine in terms of analgesia or the side-effect profile: a larger study would be needed to show a difference. The clearances of hydromorphone and morphine in the children studied were generally greater than those previously recorded, but this finding may be related to disease or treatment variables. Apart from clearance, the morphine pharmacokinetics in the study population were similar to those previously recorded. Hydromorphone may be less potent in this population of children than indicated by adult equipotency tables. The efficacy of epidural hydromorphone alone or in combination with epinephrine for postoperative analgesia was evaluated in 30 healthy women who underwent cesarean delivery with epidural anesthesia. They were assigned randomly to receive either 1.5 mg hydromorphone alone (N = 15) or 1.5 mg hydromorphone with 1/200,000 epinephrine (N = 15). Duration of analgesia (mean +/- SD) was 24.3 +/- 9.4 hours after the epidural injection of hydromorphone plus epinephrine. This was significantly greater (p less than 0.01) than the duration of 18.2 +/- 5.9 hours after the same dose of plain hydromorphone. Analgesia was more rapid in onset and significantly better at the 0.5, 1, 3, and 12 hours postoperatively in the hydromorphone-epinephrine group. Side effects including pruritus (73%), nausea (20%), and vomiting (15%) were of similar frequency with and without epinephrine. Although mean venous PCO2 (PvCO2) levels three and six hours after the hydromorphone-epinephrine dose were elevated significantly over the pre-drug PvCO2 levels, no respiratory depression was detected by an apnea monitor to which all patients were connected. The addition of epinephrine to epidural hydromorphone hastened onset and prolonged the duration of analgesia after cesarean section. nan Epidural administration of hydromorphone was evaluated using a patient-controlled analgesia (PCA) delivery system in 170 healthy women undergoing elective cesarean delivery with epidural bupivacaine who were randomly assigned to one of four epidural PCA treatment groups: group I, hydromorphone alone by bolus administration; group II, hydromorphone, with a continuous (basal) infusion; group III, hydromorphone in combination with 0.08% bupivacaine by bolus administration; or group IV, hydromorphone and bupivacaine, with a concurrent infusion of both drugs. Patients in group I required significantly less opioid medication (2.1 +/- 1.1 mg [mean +/- SD]) during the first 24 h than patients in group II (3.3 +/- 1.3 mg). Similarly, patients in group III self-administered significantly less hydromorphone (2.0 +/- 1.0 mg) and bupivacaine (23.3 +/- 11.4 mg) during the first 24 h of PCA therapy, compared with patients in group IV (hydromorphone [2.7 +/- 1.1 mg] and bupivacaine [31.5 +/- 11.6 mg]). The concomitant use of a local anesthetic or basal opioid infusion with hydromorphone via epidural PCA did not decrease the number of PCA demands or delivered doses. In addition, patients in all four groups had similar pain, sedation, discomfort, fatigue, and anxiety scores. The frequency of awakening at night to self-administer analgesic medication was not decreased when a basal infusion was used.(ABSTRACT TRUNCATED AT 250 WORDS) Epidural administration of an opioid analgesic by means of a patient-controlled analgesia (PCA) system was compared with conventional intravenous PCA for pain relief after cesarean delivery. One hundred seventeen healthy women were randomly assigned to receive hydromorphone either intravenously (IV-PCA) or epidurally (EPI-PCA) after cesarean delivery with epidural bupivacaine for operative anesthesia. The hydromorphone requirements were 3.4 and 4.2 times more in the IV-PCA group on the first (P less than 0.01) and second (P less than 0.01) postoperative days, respectively. The mean number (+/- SD) of PCA demands during the first 24 h after the operation was 105 (+/- 88) for the IV-PCA group and 33 (+/- 48) for the EPI-PCA group (P less than 0.01). This difference was also significant 24-48 h after surgery. Although the EPI-PCA group utilized significantly less opioid medication, pain and sedation scores were similar in the two treatment groups; however, a significantly larger percentage of patients in the IV-PCA group (46% vs 22%) stated that they felt drowsy during the first postoperative day. Pruritus was reported more frequently in the EPI-PCA (67%) than in the IV-PCA (33%) group. Nausea was experienced by only 10% of patients in the IV-PCA and 6% in the EPI-PCA group. There was no evidence of postoperative respiratory depression, with minimal oxygen saturation values of 93% (+/- 3%) and 94% (+/- 1%) in the IV-PCA and EPI-PCA groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) Pre-emptive analgesia represents a treatment strategy which tries to prevent the development of pain by inhibiting central reactions to peripheral sensory stimuli. In a prospective randomized double-blind placebo-controlled study, the effect of oral premedication with 4 mg of a slow-release hydromorphone preparation on postoperative piritramide consumption and subjective pain perception is being evaluated.
                96 women undergoing hysterectomy were randomly assigned to four study groups. Patients from groups 1 and 2 received hydromorphone and placebo respectively two hours before surgery, while those from groups 3 and 4 were given the same substances one hour after the end of the operation. Postoperative pain relief was provided by a patient-controlled infusion pump with piritramide. The intensity of postoperative pain as perceived by the patients was quantified on a visual analogue scale. Piritramide consumption and pain scores were recorded at 1 and 24 hours after surgery. Approval of the local Ethics Committee had been obtained beforehand as well as written informed consent from the patients.
                No significant differences in piritramide consumption were observed in between the four study groups. Visual analogue scale (VAS) ratings at 1 and 24 hours after surgery did not show any significant differences either--irrespective of whether the patients had received hydromorphone or placebo preoperatively or postoperatively.
                In our study, oral administration of 4 mg of slow-release hydromorphone did not show any greater pre-emptive analgesic effect than placebo. The efficacy of epidurally administered hydromorphone for postcesarean analgesia was evaluated in a prospective, randomized, double-blind study. Patients in group H (N = 26) received 1.0 mg of hydromorphone in preservative-free saline (total volume = 10 mL), administered epidurally. Patients in group B (N = 26) received 10 mL of 0.25% bupivacaine, administered epidurally. Both groups subsequently received intramuscular injections of hydromorphone as needed. There were significant differences between the two groups in pain score, patient assessment of analgesia quality, time to first analgesic intervention, and total dosage of hydromorphone during the first 24 hours. Nausea/vomiting and pruritus occurred more frequently in group H. No patient had a respiratory rate less than or equal to 10. There were no statistically significant differences between groups in mean times to first ambulation, first void, first passage of flatus, or hospital discharge. Twenty-five patients with pain due to advanced cancer were randomized to receive patient-controlled sc injections (PCIs) of hydromorphone (HM) versus continuous sc infusion (CSCI) of HM by means of a Pharmacia 5200 pump. Each self-injection of HM during PCI was equivalent to 4 hours of CSCI. After 3 days, a crossover occurred, and patients received the alternate treatment for 3 days. During both phases of the study, patients could request extra doses of HM from their nurses. In 22 patients able to be evaluated, pain intensity (visual analogue, 0-100 mm) at 9:00 a.m. and 4:00 p.m. was 31 +/- 23 and 28 +/- 18 mm, respectively, on PCI versus 28 +/- 18 and 27 +/- 17 mm, respectively, on CSCI [P = not significant (NS)]. The total dose of HM was 168 +/- 197 and 181 +/- 234 mg on PCI and CSCI, respectively (P = NS). No significant difference was found in nausea, drowsiness, or number of hours of sleep. The total number of extra doses of HM was 6 +/- 7 on CSCI versus 2 +/- 3 on PCI (P = .007). At the end of the study, patients chose PCI and CSCI in seven and 10 cases, respectively (P = NS; 5 patients expressed no preference). We conclude that both methods were similar in regard to effectiveness and toxic effects in short-term hospital use. Seventy-four patients were included in a double-blind, randomized, controlled trial comparing the analgesic efficacy and adverse effects of hydromorphone and morphine delivered by continuous subcutaneous infusion. Patients completed the Memorial Pain Assessment Card and a checklist of opioid-related adverse effects immediately before commencing subcutaneous infusion and 24, 48, and 72 hours later. An assessment tool was developed for the 60 patients who were too ill to complete their own questionnaire. The tool demonstrated excellent inter-rater reliability. Thirty-four percent of patients in the hydromorphone group and 27% of those in the morphine group died before completion of the study (P = 0.66). The hydromorphone group required more analgesia for breakthrough pain in the first 24 hours of the study (P = 0.03) and had a greater improvement in the behavior of frowning on movement and the comfort visual analogue scale (P = 0.08) over the course of the study. Adverse effects were rare and similar in both groups. This study found hydromorphone to be at least as effective as morphine when delivered by continuous subcutaneous infusion. nan In this pilot randomized, double-blind, cross-over study, the effectiveness and safety of hydromorphone administration by continuous subcutaneous (s.c.) infusion (mode A) and by continuous basal rate s.c. infusion + PCA (mode B) were compared in 8 cancer patients. Patients experimented with each infusion mode during 48 h. Statistical analysis was performed on data collected in 7 patients during 36 h from 22:00 h on day 1 to 10:00 h on day 3 and from 22:00 h on day 3 to 10:00 h on day 5. Mean hydromorphone dose +/- S.D. was 56.6 +/- 30.1 and 40.4 +/- 24.5 mg/36 h for modes A and B, respectively. There was no statistically significant difference observed in mean pain intensity, but the absence of significant difference may be related to the small sample size and high individual variability. Both methods provided adequate overall pain control in most patients. However, a large interindividual variation was detected. Indeed, some patients reported in the subjective questionnaire that they felt marked discomfort during hydromorphone administration with mode B. Only 2 patients chose mode B at the end of the study, but it was interesting to note that those 2 patients were the youngest of the group. This study demonstrated the effectiveness and safety of both modes of hydromorphone administration. The data suggest that it may be possible to identify particular cancer patients which can really benefit from an association of a basal rate infusion and PCA for opiate administration. Two multicenter, randomized, double-blind, crossover studies with identical designs evaluated the efficacy of oral extended-release hydromorphone (HHER) administered q24h compared with immediate-release hydromorphone (HHIR) dosed four times daily in patients with persistent moderate to severe pain. Patients titrated to a stable HHER dose were randomized to individualized doses of HHER or HHIR for 3 to 7 days before crossover to the second treatment. Primary efficacy end point was the mean of average pain intensity (API) scores, rated on a 0- to 10-point numeric scale, over the last 2 days before the pharmacokinetics/pharmacodynamics day of each double-blind period. Difference between treatments (HHER - HHIR) in study 1 was 0.17 with a 90% confidence interval (CI) (-0.01, 0.34); in study 2, difference was 0.07 with a 90% CI (-0.12, 0.26). There were no significant differences between treatments in API scores or amount of rescue medication used at any time interval within the 24-hour dosing period. No reduction in pain control occurred in patients administered HHER at the end of the 24-hour dosing period. Most treatment-emergent adverse events were opioid-related. In these studies, HHER administered q24h and HHIR dosed four times daily provided comparable analgesia at an equivalent total daily dose. The ideal oral wound care analgesic for children should be palatable, provide potent analgesia of rapid onset and short duration, and require minimal, yet appropriate, monitoring. With use of a double-blinded crossover design, we compared the efficacy and safety of oral transmucosal fentanyl citrate (OTFC) (approximately 10 micrograms/kg) with the efficacy and safety of oral hydromorphone (60 micrograms/kg) in 14 pediatric inpatients (ages 4 to 17 years) undergoing daily burn wound care in a ward setting. Pulse oximetry, vital signs, side effects, patient pain scores, and observer scores for cooperation, anxiety, and sedation were recorded. Pulse oximetry, vital signs, cooperation, sedation, incidence of nausea or vomiting, and the amount of time it took to resume normal activities were similar in both treatment groups. OTFC resulted in improved pain scores before wound care and improved anxiolysis during wound care, but at other points it was similar in effect to hydromorphone. We conclude that OTFC is a safe and effective analgesic, that it may provide minor improvements in analgesia and anxiolysis compared with hydromorphone, and that it offers a palatable alternative route of opioid administration without intravenous access for wound care procedures in children. The short elimination half-life of hydromorphone necessitates 4-hourly dosing to maintain optimal levels of analgesia in patients with chronic cancer pain. The purpose of this study was to compare the clinical efficacy and safety of controlled release hydromorphone administered every 12 hours and immediate release hydromorphone administered every 4 hours in patients with chronic severe cancer pain.
                Forty-eight patients with stable chronic severe cancer pain were randomized, in a double-masked crossover study, to controlled release hydromorphone every 12 hours or immediate release hydromorphone every 4 hours for 7 days each. Pain intensity was assessed using a visual analog scale (VAS) and the Present Pain Intensity Index of the McGill Pain Questionnaire. Nausea and sedation were also assessed using a VAS. Assessments were made by the patient four times a day at 7:00 a.m., 11:00 a.m., 3:00 p.m., and 7:00 p.m. Use of rescue hydromorphone also was recorded by the patient.
                Forty-five patients completed the study (26 women, 19 men; mean age, 57.1 +/- 13.6 years) and received a mean daily dose of 76 +/- 133 mg (range, 6-768 mg). There were no significant differences between controlled release hydromorphone and immediate release hydromorphone in overall VAS pain intensity scores (19 +/- 14 vs. 20 +/- 14 mm), ordinal pain intensity scores (1.2 +/- 0.8 vs. 1.2 +/- 0.8) and pain scores by day of treatment or time of day. The daily rescue analgesic consumption during controlled release hydromorphone and immediate release hydromorphone did not differ significantly overall (1.1 +/- 1.1 vs. 1.0 +/- 1.1 doses per day) or with respect to time of day. There were no significant differences in overall VAS sedation scores (18 +/- 18 mm vs. 19 +/- 18 mm) and in overall mean VAS nausea scores (12 +/- 15 mm vs. 11 +/- 14 mm) between controlled release hydromorphone and immediate release hydromorphone.
                Controlled release hydromorphone administered every 12 hours is as effective as immediate release hydromorphone administered every 4 hours in the management of patients with chronic severe cancer pain. The benefits of controlled release hydromorphone lie in the convenience of its capsule formulation, which can be sprinkled on soft food, and its 12-hour duration of action, which allows patients uninterrupted sleep and improved compliance. To evaluate postthoractomy analgesia in patients receiving lumbar epidural hydromorphone versus intrapleural bupivacaine.
                A randomized, prospective, double-blind study.
                A university-affiliated medical center.
                Twenty patients undergoing lateral thoracotomy for either pulmonary wedge resection, lobectomy, or pneumonectomy.
                Nine patients received epidural hydromorphone, and 11 patients received intrapleural bupivacaine in the postoperative period.
                Severity of pain was assessed using a visual analog pain scale (VAPS) (0 to 100 mm) at 1, 3, and 5 hours. Patients receiving epidural hydromorphone had a statistically significant improvement in VAPS scores. Patients who received intrapleural bupivacaine did not achieve a significant reduction in pain scores. Nine of 11 patients in the intrapleural bupivacaine group had "failed" postoperative analgesia as defined by a VAPS greater than 30. Only 3 of 9 patients in the continuous epidural hydromorphone group had "failed" analgesia.
                Epidural hydromorphone is superior to intrapleural bupivacaine in achieving satisfactory pain outcomes during the first 5 hours after thoracotomy. To evaluate the safety and efficacy of a new slow-release preparation of hydromorphone (SRH) in the treatment of cancer pain.
                Ninety-five adult patients from three Canadian Palliative Care Centers with no evidence of mental impairment received treatment for cancer pain with an oral opioid analgesic. After informed consent was obtained, patients underwent titration to a stable dose of immediate-release hydromorphone (IRH) for 48 hours, and were then randomized to receive IRH or SRH for 5 days in a double-blind basis. During day 6, a crossover took place, and patients received the alternate drug for 5 days. Pain intensity was assessed using a visual analog scale (VAS) and ordinal scale (OS). Side effects were assessed using VAS. Patients and investigators made a blinded global rating of efficacy a blinded final choice between SRH and IRH.
                In 75 assessable patients, pain intensity of the VAS and OS were (mean +/- SD) 27 +/- 21 and 1.3 +/- 0.6 on IRH, versus 29 +/- 21 (P = .13) and 1.3 +/- 0.6 (P = .19) on SRH, respectively. The total number of extra doses of opioids, global rating, and final blinded choice by both patients and investigators were not significantly different between IRH and SRH. Differences in side effects were not significant.
                Our findings suggest that SRH is as safe and effective as IRH in the treatment of cancer pain.
The studies were varied in terms of quality and methodology. However, the majority demonstrated that hydromorphone is a potent analgesic, that the effects of hydromorphone appear to be dose-related, and that adverse effects are similar to those of other mu opioid receptor agonists. Since the last version of this review, none of the new relevant studies have provided significant additional information.