morphinans and Pain--Postoperative

Oxycodone is a widely used opioid analgesic, the global use of which has increased several-fold during the last decade. This study was designed to determine the effect of age on the pharmacokinetics of intravenous oxycodone, with special reference to renal function in elderly patients.. We compared the pharmacokinetics of 5 mg of intravenous oxycodone in four groups of 10-11 patients, aged 20-40, 60-70, 70-90 years, undergoing orthopaedic surgery. Plasma concentrations of oxycodone and its noroxycodone, oxymorphone and noroxymorphone metabolites were measured for 24 hours with a liquid chromatography-tandem mass spectrometric method. The cytochrome P450 (CYP) 2D6 genotype of the patients was determined. Glomerular filtration rate (GFR) was estimated on the basis of the age, sex and serum creatinine concentration of the patient.. The pharmacokinetics of oxycodone showed age dependency. In the oldest group, the mean area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) of oxycodone was 80% greater (p < 0.001) and the apparent total body clearance of the drug from plasma (CL) was 34% lower (p < 0.05) than in the youngest group. The mean AUC(∞) of oxycodone was also 30-41% greater in the oldest group than in the age groups of 60-70 and 70-80 years (p < 0.05). Oxycodone plasma concentrations from 8 hours post-dose were >2-fold higher (p < 0.01) in patients aged >80 years than in patients aged 20-40 years. Noroxycodone AUC(∞) was increased in the oldest group compared with patients aged 20-40 and 60-70 years (p < 0.05). There were no significant sex-related differences in any of the pharmacokinetic parameters. Because 37 of the 41 patients were extensive metabolizers through CYP2D6, the effect of the CYP2D6 genotype on oxycodone pharmacokinetics could not be properly assessed. There was a linear correlation between GFR and CL (p < 0.01, coefficient of determination [r(2)] = 0.26), volume of distribution at steady state (p < 0.05, r(2) = 0.19) and AUC(∞) (p < 0.01, r(2) = 0.29) of oxycodone.. Age is an important factor affecting the pharmacokinetics of oxycodone. Following intravenous administration of oxycodone, patients aged >70 years are expected to have, on average, 40-80% higher exposure to oxycodone than young adult patients. Because oxycodone pharmacokinetics are greatly dependent on the age of the patient, it is important to titrate the analgesic dose individually, particularly in the elderly.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Analgesics, Opioid; Area Under Curve; Chromatography, Liquid; Creatinine; Cytochrome P-450 CYP2D6; Female; Genotype; Glomerular Filtration Rate; Humans; Injections, Intravenous; Male; Middle Aged; Morphinans; Orthopedic Procedures; Oxycodone; Oxymorphone; Pain, Postoperative; Tandem Mass Spectrometry; Tissue Distribution; Young Adult

In a double-blind study the relative postoperative respiratory and analgesic effects of perioperatively administered nalbuphine and fentanyl were compared in 60 females undergoing gynecological surgery under i.v. anesthesia. One milliliter (10 mg) nalbuphine was considered equipotent to 1 ml (100 micrograms) fentanyl. In the recovery period pain was assessed by visual analog score (VAS) and recovery by Pegboard scoring. Respiratory function was evaluated by continuous monitoring of respiratory frequency and end-tidal CO2 (ETCO2) and by frequent arterial blood gas analyses. The total volume of analgesic required for surgical analgesia was similar in the two groups. Patients in the nalbuphine group showed mild to moderate increases in pulse rate during the intubation phase and in blood pressure during surgery. Fentanyl was more effective in suppressing these cardiovascular responses. Within the first 15 min following recovery, increasing PaCO2 and ETCO2 as well as respiratory rates below 10/min were noted in 8 patients, who all belonged to the fentanyl group; in 4 of these patients i.v. naloxone had to be administered to reverse respiratory depression. Prolonged sedation was a common feature in patients receiving nalbuphine. It was concluded that fentanyl was superior to nalbuphine in attenuating the pressor responses to intubation and surgery. However, fentanyl was associated with respiratory depression in a considerable number of patients. The quality and duration of postoperative analgesia were similar in the two groups.

Topics: Adolescent; Adult; Aged; Anesthesia Recovery Period; Anesthesia, Intravenous; Blood Pressure; Carbon Dioxide; Double-Blind Method; Female; Fentanyl; Humans; Intraoperative Care; Middle Aged; Morphinans; Nalbuphine; Pain Measurement; Pain, Postoperative; Pulse; Random Allocation; Respiration

Postoperative analgesia in infants and young children is a topic of growing interest in pediatric anesthesia. Two systems measuring postoperative pain in this group of patients have been offered recently: CHEOPS (Childrens Hospital of Eastern Ontario Pain Scale) by McGrath et al. and OPS (Objective Pain Scale) by Hannallah et al. and Broadman et al. [3, 7, 8]. Both systems are economical and not reactive, but their validity is not satisfying. The validity of CHEOPS is based on the statements of experienced nurses, using the method of convergent validation by an expert's assertion. Hannallah and Broadman et al. judged the validity of their objective pain scale for infants and young children by statements of juveniles between 13 and 18 years of age. McGrath et al. accepted the item of spontaneous verbal communication as useful in the CHEOPS, although no such verbal comment occurred in their study on interrater and inter-item correlations. The aim of the present study was to evaluate the statistical qualification of items for measurements of the intensity of postoperative pain in young children and to investigate some aspects of their validity. MATERIAL AND METHODS. The study was performed in 54 children of ASA groups I and II aged 29.2 +/- 10.7 months. They were included in the study if they were pain-free before the operation and had no signs and symptoms of neurologic disease. The following operations were accepted: herniorrhapy, orchidopexy, circumcision, and umbilical herniorrhaphy. Premedication and general anesthesia were standardized. The patients were premedicated with midazolam 0.5 mg/kg rectally and subsequent intramuscular injections of ketamine 2.0 mg/kg with atropine 0.01 mg/kg. Anesthesia was induced and maintained by inhalation of oxygen/nitrous oxide and halothane (FiO2 0.3). All children were intubated and ventilation was controlled during the operation. After the operation and under steady-state anesthesia with 0.5 vol.% halothane and spontaneous respiration, the children received either nalbuphine 0.1 mg/kg, piritramide 0.1 mg/kg, or placebo in a randomized and double-blind manner. Respiratory and circulatory parameters were recorded for 15 min before anesthesia was discontinued. Five minutes after halothane had been discontinued the first measurement of the childrens' behavior was started with four subsequent measurements at fixed time intervals of 15 min. The measuring system was based on the six items of CHEOPS complemented by five ite

Topics: Child, Preschool; Double-Blind Method; Humans; Infant; Isonipecotic Acids; Morphinans; Nalbuphine; Pain Measurement; Pain, Postoperative; Pirinitramide; Randomized Controlled Trials as Topic; Reproducibility of Results

As most patients undergoing pulmonary surgery by postero-lateral thoracotomy have decreased preoperative pulmonary function, efficient postoperative analgesia is mandatory. Nalbuphine, a new agonist-antagonist opioid analgesic, and nefopam were compared in a double blind trial involving 60 patients. Intravenous injections of 0.3 mg.kg-1 of either drug were started when the patient evaluated his pain as being above 60 mm on a visual scale graduated from 0 to 100 mm. Repeated injections were carried out at the same dose, at the patient's request, after a minimal interval of 3 h for nalbuphine, and 6 h for nefopam. Analgesia was assessed by the visual scale, and by the patient's verbal appraisal. The respiratory and cardiovascular repercussions were evaluated clinically, and by monitoring breathing rate, blood gases, systolic and diastolic blood pressures, heart rate, and consciousness. Nalbuphine provided a convenient analgesia to all patients whereas analgesia with nefopam was insufficient in 15 out of 30 patients. No significant respiratory depression with either drug occurred. Nefopam led to a 30% increase in heart rate for one hour (p less than 0.01). Whereas patients given nalbuphine were more drowsy, although easily aroused, (p less than 0.001), nefopam was responsible for adverse effects (sweating, nausea, tachycardia with pallor, vertigo, malaise) requiring the exclusion of 7 patients from the study. Nalbuphine, although not ideal, would therefore seem to be a better analgesic than nefopam in thoracotomy patients.

Topics: Aged; Clinical Trials as Topic; Double-Blind Method; Female; Hemodynamics; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Nefopam; Oxazocines; Pain Measurement; Pain, Postoperative; Postoperative Care; Respiration; Thoracotomy

The influence of piritramide and nalbuphine versus placebo on the postoperative comfort of 54 children of ASA-group I and II in the age between 1 and 4 years was tested in a randomized double blind trial using the comfort/discomfort scale according to Büttner et al. METHODS. Operations, premedication and anesthesia were standardized. The patients were premedicated with midazolam 0.5 mg/kg rectally and a subsequent i.m. injection of ketamine 2.0 mg/kg with atropine 0.01 mg/kg. Anesthesia was induced and maintained by inhalation of oxygen/nitrous oxide and halothane (FiO2 = 0.3). All children were intubated and ventilation was controlled during the operation. After the operation, while in steady-state anesthesia with 0.5 vol% halothane and during spontaneous respiration the children received either piritramide (n = 17) or nalbuphine (n = 20) at a dose of 0.1 mg/kg, or placebo (n = 17) i.v. Respiratory and circulatory parameters were recorded for 15 min before the end of anesthesia. At 5 min after halothane had been discontinued the first measurement of the children's behavior was started, with 4 subsequent measurements at fixed time intervals of 15 min. The measuring system included the following 6 scaled items: wake-up reaction, methodical defense against stimuli, crying, facial expression, posture of the torso, posture of the legs. In addition, the waking state was scored at the same time intervals as awake, arousable, or not arousable. During the 1-h observation period all children who seemed to feel uncomfortable received midazolam i.v. at a maximal dose of 2 mg. Up to 24 h the required supplemental analgesics were noted, as were episodes of psychomotor agitation and vomiting. Written consent was obtained from the ethical committee and the children's parents. The results were tested in a 2-factorial analysis of variance (treatment factor: drugs; within-subject factor; repeated measurements). RESULTS. The 3 groups were considered to be comparable in terms of age, body weight, kind and duration of operation and circulatory values. The use of supplementary analgesics showed a significant effect in the treatment factor and in the within-subject factor: during the 1-h observation period the placebo group received midazolam significantly more often (64.7%) than the piritramide group (5.9%) or the nalbuphine group (35%). During the following 7 h 29.4% of the children of the placebo group required supplementary analgesics (piritramide: 23.5%; nalbuphine: 20%).

Topics: Child, Preschool; Double-Blind Method; Humans; Infant; Isonipecotic Acids; Morphinans; Nalbuphine; Pain, Postoperative; Pirinitramide; Randomized Controlled Trials as Topic

Nalbuphine is a new partly agonistic antagonistic opioid, that may offer some advantages especially in postoperative pain relief. We compared meperidine (1 mg kg-1) in 100 patients and nalbuphine (0.3 mg kg-1) in 70 patients, administering both agents intravenously after gynaecological operations. Standardised halothane anaesthesia without any opioid was used. After arrival in the recovery room, vigilance (sedation), quality and duration of pain relief were measured by different methods at four different times (0, 15, 30, and 60 minutes). Sedation was significantly more pronounced in the nalbuphine group, but no difference could be found in pain relief and duration between both groups. 6 patients of the n-group showed a short lasting wake-up reaction due to receptor antagonism. 36 patients had to be reinjected at the end of the first hour. We consider nalbuphine to be a safe opioid, however, the marked sedation should be taken into account.

Topics: Adult; Female; Humans; Hysterectomy, Vaginal; Meperidine; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative

The efficacy of nalbuphine, an agonist/antagonist opioid, in preventing respiratory depression from epidural morphine analgesia after thoracotomy, was assessed in a randomized double-blind placebo controlled trial. After a standardized general anaesthetic and 0.15 mg.kg-1 of epidural morphine, patients received a bolus and then a 24 h infusion of nalbuphine (200 micrograms.kg-1 + 50 micrograms.kg-1.hr-1, 100 micrograms.kg-1 + 25 micrograms.kg-1.hr-1, or 50 micrograms.kg-1 + 12.5 micrograms.kg-1.hr-1) or placebo. Blood gases, analgesia, sedation, side effects, and blood nalbuphine concentrations were assessed every two hours for the next 24 h. Fifty-three per cent of placebo-treated patients had a PaCO2 greater than 50 mmHg and 89 per cent of these received naloxone. A 200 micrograms.kg-1 bolus of nalbuphine followed by a 50 micrograms.kg-1.hr-1 infusion achieved a mean steady state blood level of 38.2 ng.ml-1 and prevented CO2 retention greater than 50 mmHg in all but two patients, neither of whom required naloxone. There was no difference in the incidence of side effects among groups, and analgesia appeared to be unaffected by nalbuphine.

Topics: Adult; Aged; Analgesia, Epidural; Carbon Dioxide; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Morphinans; Morphine; Nalbuphine; Pain, Postoperative; Placebos; Respiratory Insufficiency; Thoracotomy

Two groups of 40 patients undergoing hip replacement received either nalbuphine 0.3 mg kg-1 or morphine 0.15 mg kg-1 i.m. on up to three occasions: 1 h before operation, as soon as requested after operation, and 3 h subsequently if required. Pain intensity was assessed by the patient as severe, moderate or none, and pain relief by a "blind" nurse observer as slight, moderate or complete. Assessments of pain and sedation were carried out at 30-min intervals for 2 h and at 1-h intervals thereafter for up to 6 h. Six patients who received nalbuphine and eight who received morphine before operation required no postoperative analgesia. Ten patients in the nalbuphine group and two in the morphine group failed to obtain adequate pain relief (P less than 0.05) and were given i.v. morphine.

Topics: Analgesia; Double-Blind Method; Hip Prosthesis; Humans; Injections, Intramuscular; Morphinans; Morphine; Nalbuphine; Pain, Postoperative; Random Allocation

The side-effects of two opioid agonist-antagonists, nalbuphine and pentazocine, were assessed when used for patient-controlled postoperative analgesia. Forty ASA I or II patients scheduled for upper abdominal surgery were randomly allocated to two equal groups. The anaesthetic technique was the same for all the patients: premedication with atropine and diazepam, induction with thiopentone and suxamethonium and maintenance with fentanyl, pancuronium, nitrous oxide and halothane. Patient-controlled computer assisted analgesia (On-Demand Analgesia Computer) was started in the recovery room at least 2 h after the last administration of fentanyl. The parameters used were: a routine hourly dose (the half of that received during the previous hour), with on demand delivery of nalbuphine (15 micrograms.kg-1) or pentazocine (45 micrograms.kg-1) aliquots respectively, with a refractory period between two demands of 4 min and a total hourly maximum dose of 16 mg and 48 mg respectively. The following parameters were measured before the start of self-administration, and every hour afterwards for 24 h: systolic (Pasys) and diastolic blood pressures, heart rate, pressure-rate product (PRP), respiratory rate, end-tidal CO2 and pain (by way of a three point scale). Analgesia was assessed on a four-point scale every 6 h. The total doses of nalbuphine and pentazocine administered were 94 +/- 43 mg and 251 +/- 150 mg respectively. The only parameters significantly different between the two groups were Pasys and PRP, being higher in the pentazocine group. There were no significant differences in the side-effects (drowsiness, nausea, vomiting, headache, amnesia, logorrhoea and urine retention). All patients in both groups were satisfied with this technique.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Pressure; Clinical Trials as Topic; Heart Rate; Humans; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Pentazocine; Self Administration

Pharmacokinetic data and analgetic potency of nalbuphine hydrochloride (Nubain) under conditions of postoperative respiratory treatment and repeated dosage was investigated in a multicenter study. Patients received 20 mg nalbuphine intravenously at intervals of 3 h. Blood samples for analysis of nalbuphine plasma concentration were taken after the first injection, immediately before further medication and after the last one. Data were fitted to 2-compartment model using non-linear fit procedures. The half-life time in plasma was slightly shorter than in other studies, while the peak plasma concentrations were comparable with other results in the literature. There was no cumulation of the substance found in this study. Clinically the antagonistic effect of nalbuphine was mainly observed after neuroleptic anaesthesia. In these cases additional injections of further analgetic and sedative drugs were necessary. The clinical effect was mostly considered to be good or satisfactory. Less satisfactory effects were due to the 3 h time distance between repeated dosage. Shorter intervals could be discussed and used because of the absence of cumulation of nalbuphine in this study.

Topics: Adolescent; Adult; Female; Humans; Male; Morphinans; Multicenter Studies as Topic; Nalbuphine; Pain, Postoperative; Postoperative Period

Topics: Aged; Cardiovascular Diseases; Digestive System Diseases; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Pentazocine; Randomized Controlled Trials as Topic

A group of 40 women having undergone abdominal gynecological operations were studied for the comparative evaluation of nalbuphine and morphine. The analgetics were used to relieve postoperative pain in the technique of double blind trial. 20 women were administered 20 mg of nalbuphine and 20 women were administered 10 mg of morphine. Within 6 hours following the administered of each of the drugs, the authors evaluated the analgetic effectiveness, haemodynamic, ventilatory and gasometric parameters. Most of the women showed satisfactory and comparable analgetic effectiveness of the two drugs for six hours. No influence was found of any of the analgetics on the physiological parameters examined. The frequency and intensification of side-effects were the same both after administering nalbuphine and morphine. In the authors' opinion, in a proper dose, nalbuphine is an analgetic equal to morphine with respect to analgetic effectiveness and time of pharmacological action.

Topics: Adult; Double-Blind Method; Female; Genitalia, Female; Humans; Middle Aged; Morphinans; Morphine; Nalbuphine; Pain, Postoperative

The aim of the study was a comparison of the side-effects and efficacy of nalbuphine, piritramide, and placebo in patients during recovery from halothane anesthesia.. Neurosurgical (vertebral surgery) and otolaryngological patients (surgery of face and neck) were operated under halothane anesthesia. Postoperatively 20 patients received 20 mg nalbuphine, 21 patients 15 mg piritramide, and 19 patients 0.9% NaCl for pain therapy in a randomized and double-blind manner. Respiratory function was monitored by blood gas analysis, hemodynamic function by noninvasive measurements. The analgetic and sedative effects were estimated by the patients (visual analog scale) and the investigator (4-point scale). If the treatment was ineffective, the study was interrupted and a known analgesic was prescribed.. The noninvasively measured hemodynamic parameters were unchanged. On the other hand, in the nalbuphine group mean arterial pCO2 increased significantly (max. 55.4 mmHg after 20 min), over the piritramide group (max. 51.2 mmHg before treatment) and the placebo group (max. 55.1 mmHg before treatment). Drowsiness, in 8 patients in each of the treatment groups and 3 patients in the placebo group, was the most frequent side-effect. After nalbuphine the pain threshold was significantly higher than after treatment with piritramide and placebo. The study was interrupted because of inefficacy in no patients from the nalbuphine group, 2 patients from the piritramide group, and 6 patients from the placebo group. There were no differences in the sedative effects.. Nalbuphine seems to have better analgesic effects then piritramide. Both cause no hemodynamic alterations.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anesthesia, Endotracheal; Blood Pressure; Cervical Vertebrae; Clinical Trials as Topic; Halothane; Humans; Intervertebral Disc Displacement; Isonipecotic Acids; Lumbar Vertebrae; Morphinans; Nalbuphine; Otorhinolaryngologic Diseases; Oxygen; Pain Measurement; Pain, Postoperative; Pirinitramide; Random Allocation

Little is known about the effects of mixed opioid analgesics on gastrointestinal propulsion. In 20 patients, nalbuphine (0.1 mg/kg) was given after routine neuroleptanesthesia consisting of 70 micrograms/kg droperidol, 7 micrograms/kg fentanyl, and N2O/O2 (3:1) ventilation, to study its effect on gastrointestinal motility in the postoperative period. For comparison, another group of patients (n = 20) undergoing similar interventions received placebo (0.9% NaCl) at the end of the procedure. Gastrointestinal transit time was determined by measuring the exhaled H2 concentration following gastric lactulose administration. As lactulose is degraded only in the cecum, resulting in the release of hydrogen, the arrival of the polysaccharide at the terminal ileum could thus be determined. Compared to placebo, gastrointestinal transit was significantly longer in patients after nalbuphine (mean transit time 270 min vs 380 min). Pain estimation by visual analogue scale (VAS 0-10) suggested an antagonistic effect at the 10th and 20th min postoperatively, as pain scores in the nalbuphine group were higher when compared to placebo (3.5 vs 1.8 and 2.5 vs 1.4). There was a similar pain score in both groups (1.3 vs 1.4) 30 min after drug administration. However, there was significantly better pain relief after nalbuphine (0.7 vs 1.4 and 0.7 vs 1.1) in the late postoperative period (120th and 240th min). When given after potent opioids, it must be borne in mind that the antagonistic effect of nalbuphine is initially apparent. The agonistic potency of the compound will come into effect around the 30th min post-injection. Delayed gastrointestinal transit after nalbuphine is explained by agonist-like effects on peripheral opioid receptors in the gut.

Topics: Adult; Clinical Trials as Topic; Female; Fentanyl; Gastrointestinal Transit; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Neuroleptanalgesia; Pain, Postoperative; Placebos; Prospective Studies; Random Allocation; Time Factors

A randomized, double-blind comparison of nalbuphine 30 mg or 60 mg by mouth and dihydrocodeine 30 mg by mouth was conducted in 75 patients with moderate to severe pain after surgery for dental extractions under general anaesthesia. A significant reduction in pain intensity followed each treatment and persisted throughout the 4-h observation period after nalbuphine, but only for 3 h after dihydrocodeine was given. Reduction in pain intensity was significantly greater 2, 3 and 4 h after the use of nalbuphine 60 mg than following dihydrocodeine 30 mg, and the mean total pain intensity difference was greater following nalbuphine 60 mg than following dihydrocodeine. Nalbuphine 60 mg effectively provided complete or good pain relief in more than 50% of the patients and only three patients in this group required additional analgesia during the period of observation, compared with nine patients in each of the other groups. However, the patients who received nalbuphine 30 mg had a significantly higher mean pain intensity before treatment than those in the other groups. The side-effects encountered were those typical of opioid medication; there were no statistically significant differences between the groups.

Topics: Administration, Oral; Adolescent; Adult; Anesthesia, Dental; Anesthesia, General; Clinical Trials as Topic; Codeine; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Random Allocation; Time Factors; Tooth Extraction

The effect of nalbuphine on the respiratory depression, pruritus and analgesia induced by epidural morphine was determined in a randomized, prospective, double-blind, placebo-controlled fashion. Twenty ASA physical status I women received 0.1 mg.kg-1 epidural morphine at induction of general anaesthesia for elective total abdominal hysterectomy. Group 1 (n = 14) received 0.3 mg.kg-1 nalbuphine intravenously six hours after the epidural morphine administration. Group 2 (n = 6) received saline. Prior to agent administration, six patients from the nalbuphine group and four patients from the saline group had respiratory depression indicated by a PaCO2 greater than 45 mmHg. After nalbuphine administration the PaCO2 (mean +/- SE) decreased from 49.5 +/- 1.2 mmHg to 42.5 +/- 0.7 mmHg (p less than 0.005) while there was no significant change after saline administration. Nine of the 14 patients receiving nalbuphine appeared to become more sedated, despite an improvement in ventilation. Pruritus was antagonized by 0.1 mg.kg-1 nalbuphine (p less than 0.006). There was no reversal of analgesia after administration of 0.3 mg.kg-1 nalbuphine.

Topics: Adult; Analgesia, Epidural; Carbon Dioxide; Depression, Chemical; Double-Blind Method; Female; Humans; Hysterectomy; Morphinans; Morphine; Nalbuphine; Pain Measurement; Pain, Postoperative; Prospective Studies; Pruritus; Random Allocation; Respiration

A randomised, double blind study was conducted to compare the efficacy and safety of nalbuphine or pentazocine with midazolam in patients undergoing minor oral surgery under local analgesia. Forty patients, aged between 17 and 48 years and in American Society of Anesthesiologists A.S.A. Class I participated. The results confirmed that the use of either nalbuphine (0.2 mg/kg) or pentazocine (0.5 mg/kg) allowed for a significant reduction in the mean dosage of midazolam required to produce satisfactory sedation when compared with trials where midazolam was used alone. Thus a mean midazolam, 0.087 mg/kg (nalbuphine group) or 0.081 mg/kg (pentazocine group) was required compared with 0.17 mg/kg (Aun et al., 1984) and 0.19 mg/kg (Skelley et al., 1984). Inadvertent overdosage with midazolam is prevented as the onset of sedation and its end-point are more obvious. No adverse cardiovascular or respiratory side effects were noted. The recovery rate for both groups was similar. Ninety-five per cent (39 of 40) of patients were able to walk unaided at 2 h post operation. At this time significantly more patients in the nalbuphine group were pain free (p less than 0.001). Both combinations provided excellent operating conditions with a high degree of safety and high patient acceptability. As the nalbuphine group enjoyed a more comfortable post-operative period this combination is favoured.

Topics: Adolescent; Adult; Anesthesia Recovery Period; Anesthesia, Dental; Double-Blind Method; Female; Humans; Hypnotics and Sedatives; Injections, Intravenous; Male; Midazolam; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Pentazocine; Preanesthetic Medication

Nalbuphine and fentanyl were compared as analgesic components of intravenous conscious sedation with diazepam in a double-blind, prospective trial of 50 patients undergoing elective oral surgery. Subjects were evaluated for intensity of pain, pain relief, sedation, anxiety, recall, and vital signs at systematic observation points intraoperatively and postoperatively. At the conclusion of surgery, 88% who received nalbuphine and 87% treated with fentanyl indicated complete pain relief. One observed adverse reaction was attributed to the combination of fentanyl and the sedative component diazepam. No statistically significant differences were observed between nalbuphine and fentanyl treatments.

Topics: Adult; Anesthesia, Dental; Diazepam; Double-Blind Method; Drug Therapy, Combination; Evaluation Studies as Topic; Female; Fentanyl; Humans; Infusions, Intravenous; Male; Middle Aged; Morphinans; Nalbuphine; Pain Measurement; Pain, Postoperative; Preanesthetic Medication; Prospective Studies

A double blind randomized study was done to compare Nalbuphine 20 mg I.M. to pentazocine 30 mg I.M. for postoperative pain relief after orthopedic surgery. This dose of pentazocine was choosen according to reports in the literature and to our standard practice. Sixty patients entered the study and were observed regularly till up 6 h post injection. The test drug was given when a pain score of 6 was shown on a VAS from 0 to 10. Onset, duration and quality of pain relief were significantly superior for nalbuphine with 50% of the patients still having no or only moderate pain at the end of the observation period. Cardiovascular and side effect were in both groups minor.

Topics: Adult; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Orthopedics; Pain, Postoperative; Pentazocine; Random Allocation

The analgesic efficacy and safety of butorphanol tartrate are discussed in 2 groups of patients who underwent urological procedures. The first group of 83 patients is presented as a retrospective review of the postoperative use of butorphanol. The second group of patients was involved in a double-blind, randomized comparative trial of butorphanol (2 or 4 mg) and meperidine (80 mg) for the relief of moderate to severe pain due to renal colic. Eighty-three patients with documented upper urinary tract calculi were evaluated for efficacy; 120 patients were evaluated for safety. Butorphanol 4 mg (i.m.) was more effective than butorphanol 2 mg (i.m.) and equivalent to meperidine 80 mg (i.m.). There were no statistically significant differences among the three treatment groups in regard to side effects. Overall, in the urology patients studied, butorphanol was found to be an effective and well tolerated agent that possesses important safety advantages when compared with the narcotic analgesics.

Topics: Adolescent; Adult; Aged; Butorphanol; Colic; Double-Blind Method; Female; Humans; Kidney Diseases; Male; Meperidine; Middle Aged; Morphinans; Pain Measurement; Pain, Postoperative; Prostatic Diseases; Random Allocation; Retrospective Studies; Urinary Calculi

In this study, the patient-controlled analgesia (PCA) technique was used to compare the suitability of butorphanol with that of morphine in relieving postoperative pain. Twelve patients, 19-77 years old, who had abdominal surgery, used the PCA device through the first 24-hour postoperative period. Results showed that all patients expressed satisfaction with the PCA technique. Analysis of the degree of discomfort according to the verbal description scale, recordings of respiratory rate, and assessment of sedation status showed no significant differences between patients who received butorphanol and those who received morphine. Patients were able to maintain acceptable analgesia with minimal sedation. There were no adverse side effects reported with butorphanol.

Topics: Adult; Aged; Butorphanol; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Random Allocation; Self Administration

A double-blind investigation was undertaken to compare the efficacy of nalbuphine and fentanyl in the prevention of pain after day case termination of pregnancy. Forty patients were allocated randomly to receive nalbuphine 0.25 mg/kg or fentanyl 1.5 micrograms/kg immediately before induction of anaesthesia. The patients completed scores for pain and nausea, and performed a reaction time test to assess recovery. An observer assessed patient appearance at 1, 2 and 4 hours postoperatively. Patients who received nalbuphine had significantly lower pain scores at 1 hour (p less than 0.01) and 2 hours (p less than 0.05) and required significantly (p less than 0.05) less postoperative analgesia. No significant differences were found between the groups for incidence of nausea or for observer assessment of appearance. There was some evidence of psychomotor impairment at 2 hours in the nalbuphine group. Freedom from Controlled Drug Act regulations and improved analgesia with nalbuphine, render it more satisfactory for day case surgery than the more commonly used fentanyl.

Topics: Abortion, Induced; Adolescent; Adult; Ambulatory Surgical Procedures; Anesthesia Recovery Period; Anesthesia, General; Anesthesia, Obstetrical; Double-Blind Method; Female; Fentanyl; Humans; Morphinans; Nalbuphine; Pain, Postoperative; Pregnancy

A double-blind investigation was conducted to compare nalbuphine with morphine for the control of pain after unilateral orchidopexy. Fifty boys under 11 years of age were allocated randomly to receive intramuscular nalbuphine 0.2 mgkg-1 or morphine 0.2 mgkg-1 immediately after induction of anaesthesia. Pain was assessed on a three-point scale, 1, 2 and 4 h after injection and on the morning following operation. Side-effects were also recorded. There were no significant differences between the two drugs in either the provision of analgesia, or the incidence of the principal side-effects of vomiting and sweating. There was a high incidence of vomiting in both groups. Nalbuphine is a satisfactory alternative to morphine for post-orchidopexy pain and may offer the advantages of greater safety and convenience.

Topics: Child; Clinical Trials as Topic; Cryptorchidism; Double-Blind Method; Humans; Male; Morphinans; Morphine; Nalbuphine; Pain, Postoperative; Random Allocation

To determine the safety, efficacy, and the ventilatory responses to carbon dioxide (CO2) of epidurally administered butorphanol or morphine, 122 healthy women who underwent cesarean section with epidural anesthesia were studied. Patients were randomly assigned to receive one of four epidural regimens for the relief of postoperative pain: 5 mg morphine (n = 32), 4 mg butorphanol (n = 30), 2 mg butorphanol (n = 29), or 1 mg butorphanol (n = 31). Epidural morphine provided satisfactory analgesia with slow onset and long duration of approximately 21 hr. When butorphanol was administered, analgesia of rapid onset was seen with increasing duration and effectiveness observed with increasing dose; approximately 8 hr when using 4 mg. Sixty-two percent of the patients who received morphine had pruritus. Somnolence was the main side effect encountered in patients who received epidural butorphanol. The ventilatory response to CO2 was depressed after morphine and after 2 and 4 mg butorphanol, but the duration of depression was more prolonged after morphine. It is concluded that epidural butorphanol is effective in providing pain relief after cesarean section with minor side effects. However, patients must be observed closely because of possible respiratory depression.

Topics: Butorphanol; Carbon Dioxide; Cesarean Section; Dose-Response Relationship, Drug; Double-Blind Method; Drug Evaluation; Female; Humans; Injections, Epidural; Morphinans; Morphine; Pain Measurement; Pain, Postoperative; Pregnancy; Random Allocation; Respiration; Time Factors

It has been suggested in various studies that the opiate agonist/antagonist nalbuphine (Nubain) provides for effective reversal of the respiratory depression after fentanyl while maintaining postoperative analgesia. We tested this hypothesis in a relatively large number of patients. The study consisted of two parts: one randomized open, the other randomized double-blind, each with 150 ASA I or II patients aged 18 to 65 years. After premedication with atropine 0.5 mg and flunitrazepam 0.5 mg, anaesthesia was induced with flunitrazepam 0.5 mg, fentanyl 0.1 mg, and etomidate 10 mg and maintained with N2O/O2, 2/1, and additional increments of 0.1 mg fentanyl as required. Relaxation for intubation and surgery was obtained with vecuronium, atracurium, or pancuronium depending on the expected duration of anesthesia. After the operation the patients were extubated and the residual effects of fentanyl antagonized with naloxone 0.05 mg or nalbuphine 10 mg or 20 mg i.v. (randomized open or double-blind). The patient data and fentanyl dosages are given in Table 1. Postoperative pain was assessed by the time interval between administration of the opiate antagonist and the requirement for the first analgesic medication. Figures 1a and b and Table 2 indicate that after nalbuphine 20 mg the first analgesic was required significantly later than after naloxone 0.05 mg (median 115 or 123 min after nalbuphine 20 mg vs 56 or 52 min after naloxone 0.05 mg; P less than 0.02). There was no significant difference between nalbuphine 10 mg and naloxone 0.05 mg. The open and double-blind studies gave virtually identical results. Sixty minutes after administration of 20 mg nalbuphine, vigilance was significantly reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adolescent; Adult; Aged; Anesthesia, Inhalation; Arousal; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Fentanyl; Humans; Middle Aged; Morphinans; Nalbuphine; Naloxone; Pain, Postoperative

A double-blind, sex-stratified, study compared the analgesic efficacy and side effects of nalbuphine 10 mg ml-1 (group N) and buprenorphine 0.15 mg ml-1 (group B) administered as a continuous infusion (0.2 ml kg-1/24 h), after abdominal surgery. Patients could request additional i.m. analgesic for pain. The study groups were well matched. The trial was stopped after 55 patients had been studied (nalbuphine 29, buprenorphine 26), because nine patients in the nalbuphine group had inadequate pain relief (P less than 0.01) shortly after surgery (mean 2.5 h). Analysis of the results on an "intention to treat" basis showed that the patients who received buprenorphine had significantly greater pain relief at 1, 3, 6 and 20 h after surgery. Patients who received buprenorphine were assessed by the physiotherapist to have less pain and better chest expansion. More additional analgesic was given to the patients receiving nalbuphine. In the patients receiving buprenorphine, the mean ventilatory rate was less (N = 19 b.p.m., B = 14 b.p.m.) (P less than 0.001) and the increase in PaCO2 was greater (N = 0.5 kPa, B = 1.1 kPa) (P less than 0.001), compared with the value before operation. Side effects were equal, and no serious adverse effects were observed in either group.

Topics: Abdomen; Adolescent; Adult; Aged; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Physical Therapy Modalities; Respiration

The analgesic efficacy and side effect profile of nalbuphine 20 mg IV and of nalbuphine 40 mg IV were compared to those of meperidine 75 mg IM in the immediate postoperative period. Pain intensity, pain relief, additional analgesic requirements and the overall acceptability of the treatment were recorded for 150 patients. No significant differences were found between the groups for any of the efficacy variables. Peak analgesic effects occurred at 15 minutes in both nalbuphine groups and at 30 minutes in the meperidine group. The mean time to additional analgesic medication was approximately 207 minutes in each group. The incidence of nausea and vomiting with meperidine was 22 per cent (95 per cent confidence interval 10 to 34 per cent) and with nalbuphine 20 mg the incidence was two per cent (95%CI -2 to 6 per cent). This difference was significant (p less than 0.01). The difference between nalbuphine 40 mg (10 per cent, 95%CI 1 to 19 per cent) and meperidine, was not considered statistically significant (p = 0.17). The analgesic efficacy of nalbuphine 20 mg was indistinguishable from that of nalbuphine 40 mg and from that of meperidine 75 mg. The significantly lower incidence of nausea and vomiting with nalbuphine is a major advantage for a recovery room analgesic.

Topics: Abdomen; Adult; Bone and Bones; Double-Blind Method; Female; Humans; Male; Meperidine; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative

The safety and efficacy of intravenous doses of dezocine (5 or 10 mg), butorphanol (1 mg), and placebo were compared in a double-blind study in 160 patients with moderate to severe postoperative pain. Analgesic efficacy was assessed for 6 hours after each dose. Mean pain relief scores were consistently higher, indicating greater pain relief, for the three active treatment groups than for the placebo group. The 10-mg dezocine dose was the most effective treatment, and 5 mg of dezocine was comparable to 1 mg of butorphanol. In the 2 hours after the first dose, 32% of the 10-mg dezocine group, 53% of the 5-mg dezocine group, 65% of the butorphanol group, and 88% of the placebo group withdrew from the study because of unsatisfactory pain relief. The differences in these percentages were statistically significant (P less than 0.05) between each active therapy group and the placebo group, and between the 10-mg dezocine group and the butorphanol group. Changes in degree of sedation were similar in the three active therapy groups. Adverse reactions were rare, mild, and equally distributed among the four treatment groups. We conclude that 10 mg of dezocine is superior to 1 mg of butorphanol, and that 5 mg of dezocine is as effective as 1 mg of butorphanol for the relief of moderate to severe postoperative pain.

Topics: Adolescent; Adult; Aged; Analgesics, Opioid; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Clinical Trials as Topic; Cycloparaffins; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphinans; Pain, Postoperative; Placebos; Tetrahydronaphthalenes

The postoperative treatment of pain in children is often inadequate: Periphal acting analgetics are not sufficient, opioids are believed to be dangerous because of their respiratory depression. Nalbuphine and tramadol are two narcotics with only a few side effects. The aim of this trial was to investigate the efficacy and safety of these drugs in postoperative pain therapy in children aged 1-9 years. 30 children in each group received in a double-blind and randomized manner either 0.15-0.2 mg/kg nalbuphine or 0.75-1.0 mg/kg tramadol im. Pain intensity and sleep-awake behaviour were documented by a visual analogue scale for 24 h. After 1 h 70% of the patients in both groups had no pain and were sleeping. There was no change in heart rate and systolic blood pressure. Only the diastolic blood pressure decreased as did the respiratory rate, while the tcpCO2 estimated in some patients remained constant. Narcotic reinjections were necessary three times in the nalbuphine group and four times in the tramadol group. Typical opioid side effects were found to be equal in both groups.

Topics: Blood Pressure; Body Temperature; Carbon Dioxide; Child; Child, Preschool; Clinical Trials as Topic; Cyclohexanols; Double-Blind Method; Female; Heart Rate; Humans; Infant; Male; Morphinans; Nalbuphine; Pain, Postoperative; Random Allocation; Respiration; Tramadol

The analgesic potency, efficacy, duration of action and side-effects of buprenorphine (Temgesic) 0.3 mg and 0.6 mg were compared with those of pentazocine (Sosegon) 30 mg and 60 mg in 100 male patients who had undergone orthopaedic surgical procedures. The drugs were given by intramuscular injection 30 minutes before completion of the surgical procedure, and the quality of pain relief and incidence of side-effects were assessed at 30-minute intervals for at least 6 hours. Buprenorphine was shown to be safe, to be more potent and to have a longer duration of action than pentazocine, and to result in less nausea, vomiting and euphoria, but it was associated with a higher incidence of postoperative sedation than pentazocine.

Topics: Adolescent; Adult; Buprenorphine; Clinical Trials as Topic; Humans; Male; Morphinans; Pain, Postoperative; Pentazocine; Random Allocation; Time Factors

In a double-blind controlled study, epidural buprenorphine 0.3 mg was compared with 4 mg of epidural morphine for postoperative pain relief the first 24 hours after major orthopaedic surgery. The degree of analgesia was equal and satisfactory in both groups. Duration of action was 620 minutes with buprenorphine and 580 minutes with morphine, which was not significantly different. The only serious side effects were recorded in the morphine group, with two patients complaining of pruritus and five of urinary retention. In conclusion, epidural buprenorphine did not offer any advantages in preference to morphine for postoperative pain relief following orthopaedic surgery.

Topics: Adolescent; Adult; Aged; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Epidural Space; Female; Humans; Injections; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative

This double-blind, randomized, parallel, placebo-controlled study evaluated the analgesic effects of single oral doses of 30 mg nalbuphine, 650 mg acetaminophen, and the contribution of each to the efficacy of their combination in 128 hospitalized patients with postoperative pain. Subjective reports of patients evaluated each hour for 6 hours were used as indices of analgesic response. Both nalbuphine and acetaminophen were significantly superior to placebo for most measures of total and peak analgesia. The interaction contrast between nalbuphine and acetaminophen was not significant for any analgesic measurements, indicating an additive effect of the components. The combination was the most effective treatment, followed by nalbuphine, acetaminophen, and placebo. Effects of the combination were significantly different from those of acetaminophen at 4, 5, and 6 hours and from those of placebo at 1 to 6 hours. There was no significant difference in the frequency or intensity of side effects among the groups. The combination of nalbuphine and acetaminophen appears to be a therapeutically useful combination.

Topics: Acetaminophen; Administration, Oral; Adolescent; Adult; Aged; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Random Allocation

Topics: Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Humans; Morphinans; Pain; Pain, Postoperative

The safety and efficacy of single intramuscular doses of dezocine (10 or 15 mg) were compared with butorphanol (2 mg) and placebo in 157 patients with moderate to severe postoperative pain. A verbal pain intensity scale, an analog pain intensity scale, and a verbal pain relief scale were used to record the patients' subjective assessments. The results of this study indicate that a single 10 or 15 mg intramuscular injection of dezocine is safe and more effective than placebo for four to six hours, respectively, in the treatment of moderate to severe postoperative pain (P less than .05). During the first hour of treatment the pain relief afforded by 2 mg of butorphanol was significantly greater than that afforded by 10 mg of dezocine (P less than .05), but both doses of dezocine provided long-lasting relief. The scores on all three efficacy scales were highest with the 15 mg dose of dezocine after the first hour, while the 10 mg dose of dezocine and butorphanol were compared during this period. Nausea and vomiting were the most commonly reported side effects; injection site reactions were reported more frequently in the butorphanol group.

Topics: Acute Disease; Adolescent; Adult; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Clinical Trials as Topic; Consumer Behavior; Cycloparaffins; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Nausea; Pain, Postoperative; Placebos; Tetrahydronaphthalenes; Time Factors; Vomiting

A double-blind comparison of some analgesic and gastrointestinal effects of nalbuphine and pethidine was performed in 28 women undergoing laparoscopic sterilisation. The opioid was given as an initial loading dose prior to the induction of general anaesthesia and further doses were given on demand in the postoperative period to achieve and maintain adequate pain relief. Gastric emptying in the immediate postoperative period was also assessed in each patient by measuring the rate of absorption of orally administered paracetamol. Nalbuphine was equally effective as pethidine as a postoperative analgesic, but may have been a less effective supplement to anaesthesia in the doses used in this study. Gastric emptying was profoundly depressed in all patients irrespective of which analgesic was used.

Topics: Absorption; Acetaminophen; Adult; Animals; Double-Blind Method; Drug Evaluation; Female; Gastric Emptying; Humans; Meperidine; Morphinans; Nalbuphine; Pain, Postoperative; Random Allocation; Vomiting

A randomized, double-blind, placebo-controlled study of buprenorphine was carried out in 20 patients after cholecystectomy. The drug was given on "patient demand" either i.m. (0.15 mg) or sublingually (0.2 mg) with a minimum dose interval of 30 min. Over the 24-h study period the mean demand by the sublingual route was 0.8 mg (range 0.6-1.2 mg) and by the i.m. route 0.66 mg (range 0.45-0.9 mg). Pain relief, by visual analogue scales and grading, was similar. Plasma buprenorphine concentrations varied more after sublingual administration. Either route was effective for the treatment of pain when administered by "patient demand".

Topics: Administration, Oral; Adolescent; Adult; Aged; Buprenorphine; Cholecystectomy; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Pain, Postoperative; Tongue

Eighty otherwise healthy women, aged 22-64 years, admitted for elective hysterectomy were studied in a prospective randomized trial. The aim was to compare two different postoperative pain relief schedules--one with the analgesic given at regular intervals and the other with the analgesic given on demand. All the patients had a neuroleptanaesthesia with fentanyl. Forty patients received an initial dose of buprenorphine 0.3 mg intravenously before termination of anaesthesia and continued with sublingual buprenorphine 0.4 mg 6 hourly postoperatively (regular interval (RI) group). Forty patients received the standard postoperative medication, meperidine 1 mg/kg on demand in the recovery room, followed by ketobemidone 5 mg subcutaneously on demand in the surgical ward (on demand (OD) group). There was no difference between groups concerning pain relief following a single dose of analgesic (P greater than 0.05, type II error 1-5%). In the recovery room 17.5% of the patients in the RI group received an analgesic compared to 87.5% in the OD group (P less than 0.05). Among patients in the RI group who had previously got injections for postoperative pain relief on demand 95% preferred regular interval sublingual buprenorphine for future treatment. The nurses found that 90% of the patients in the RI group were treated adequately compared to 62.5% of the patients in the OD group (P less than 0.05). It is concluded, that regular interval preventive pain relief is superior to conventional on demand analgesic therapy in postoperative pain.

Topics: Adult; Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Drug Administration Schedule; Female; Humans; Hysterectomy; Meperidine; Middle Aged; Morphinans; Pain, Postoperative

Sixty postoperative orthopaedic patients were randomly assigned to three equal groups to study, in a double-blind fashion, the analgesic effects, durations of action and side effects of the extradural administration of lofentanil 5 micrograms, buprenorphine 0.3 mg or physiological saline. No systemic analgesics were given before, during or after surgery, and all the patients had operations on the lower extremities under extradural analgesia (lignocaine and bupivacaine). Eleven millilitre of the test drug was injected at T12-L1 as soon as pain occurred in the postoperative period. We observed a long duration of action and a marked analgesic effect with lofentanil, a shorter duration of action and less pain suppression with buprenorphine and a rather marked placebo effect after saline. The only side effect noticed in this study was drowsiness in three patients in the lofentanil group and in two patients in the buprenorphine group.

Topics: Adult; Aged; Analgesics, Opioid; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Epidural Space; Female; Fentanyl; Humans; Injections; Male; Middle Aged; Morphinans; Pain, Postoperative

The relative performance of three analgesic rating scales--visual pain analog, verbal pain intensity, and verbal pain relief--was assessed in clinical trials with 1,497 patients and a variety of pain models. The scales correlated strongly with one another, with inconsistent and generally minimal differences in sensitivity. Overall, the verbal relief scale tended to be slightly more sensitive than the pain analog rating, which in turn showed a small advantage over the verbal pain intensity assessment. When the scores derived from the categorized ratings 1 hour after drug dosing (generally the time of peak effect) were analyzed, there was little difference whether a parametric or nonparametric approach was taken. When the cumulative measures of overall effect over 6 hours were considered, however, the nonparametric approach was decidedly more powerful. There was a similar pattern when the analog scores were analyzed. This unanticipated finding appears to be due to the cumulative measures (from all three scales) being more skewed toward the lower end of their respective ranges than are the 1-hour scores. A composite efficacy variable was defined, incorporating data from the three primary scales; this measure was found to be generally comparable in sensitivity to the individual scales and may be useful as a global summary of response. While our investigation provides evidence that any of the ratings considered will accurately reflect analgesic response, the verbal relief scale was the most sensitive and might be the best choice if a single measure is desired.

Topics: Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Clinical Trials as Topic; Cycloparaffins; Double-Blind Method; Humans; Morphinans; Morphine; Pain; Pain, Postoperative; Tetrahydronaphthalenes

Topics: Administration, Oral; Adult; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Humans; Injections, Intramuscular; Meperidine; Morphinans; Mouth Floor; Pain, Postoperative

In a double-blind clinical trial of 48 patients, nalbuphine, morphine, and pethidine were compared by on-demand intravenous analgesia during the first 24 hours after cholecystectomy. Overall pain relief (visual analogue score) was recorded by the patients as 50 (SEM 4) for nalbuphine, 44 (SEM 4) for morphine and 53 (SEM 5) for pethidine. These scores were not significantly different. The mean demand for each drug over the 24-hour period was 70 (SEM 12) mg for nalbuphine, 46 (SEM 6) mg for morphine and 614 (SEM 49) mg for pethidine. Pain on movement, either during deep breathing or turning, was found to be less well controlled after nalbuphine (70, SEM 2), and pethidine (67 SEM 7) than after morphine (52, SEM 5; p less than 0.01). The incidence of side effects was similar with each drug. Nalbuphine is a useful postoperative analgesic, as effective as pethidine. Nalbuphine 15 mg is apparently equipotent with morphine 10 mg or pethidine 120 mg by this mode of administration.

Topics: Adult; Cholecystectomy; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Infusions, Parenteral; Male; Meperidine; Middle Aged; Morphinans; Morphine; Nalbuphine; Pain, Postoperative; Self Administration; Therapeutic Equivalency; Time Factors

Nalbuphine hydrochloride (Nubain; Du Pont Pharmaceuticals), a synthetic agonist-antagonist analgesic, in a dose of 20 mg was compared with pethidine 100 mg in 60 patients after elective surgery in a random double-blind study. Both drugs were given intramuscularly on the first day after surgery. The pain intensity and visual analogue scales would seem to indicate that nalbuphine has a longer duration of action than pethidine (P less than 0,05). The respiration rates in the pethidine group were significantly more depressed 30 minutes after the injection than in the nalbuphine group (P less than 0,05). Nalbuphine caused less depression of both systolic and diastolic blood pressure at both 30 and 60 minutes (P less than 0,001). The results of the study show that nalbuphine, in the dose used here, may prove to be a useful substitute for pethidine.

Topics: Adolescent; Adult; Aged; Blood Pressure; Clinical Trials as Topic; Double-Blind Method; Humans; Meperidine; Middle Aged; Morphinans; Nalbuphine; Orthopedics; Pain, Postoperative; Random Allocation; Respiration

Topics: Adolescent; Adult; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Molar, Third; Morphinans; Nalbuphine; Pain, Postoperative; Pentazocine; Prospective Studies; Random Allocation; Tooth Extraction

A controlled investigation was conducted to compare the effectiveness of morphine and nalbuphine in the prevention of pain and restlessness after tonsillectomy in children. Sixty children between 4 and 12 years old were randomly allocated to receive intramuscular morphine 0.2 mg/kg, nalbuphine 0.3 mg/kg or no medication approximately 5 minutes before the conclusion of surgery. Pain and restlessness were assessed 1 and 2 hours after injection, and side effects were recorded. The assessments were made double-blind. Both nalbuphine and morphine decreased restlessness and pain 1 hour (p less than 0.01) and 2 hours (p less than 0.05) after surgery. No significant differences were found between the two groups of patients who received opioids. Both nalbuphine and morphine caused more drowsiness than placebo 2 hours after surgery (p less than 0.001). Other side effects were uncommon. Nalbuphine may offer advantages compared with morphine in regard to safety and convenience of use for the treatment of post-tonsillectomy pain in children.

Topics: Child; Child, Preschool; Clinical Trials as Topic; Female; Humans; Male; Morphinans; Morphine; Nalbuphine; Pain, Postoperative; Psychomotor Agitation; Tonsillectomy

Fifty-one patients undergoing cholecystectomy received a single dose of buprenorphine 4.5-12 micrograms kg-1 at induction. Median duration of analgesia after surgery was 6 h. Multiple regression analysis showed the duration of analgesia to be slightly dependent on the age of the patient. No relationship was found between the duration of analgesia and the weight-related dose of buprenorphine, the age, sex or body weight of the patient, the duration of anaesthesia, or the dose of droperidol or thiopentone administered.

Topics: Adjuvants, Anesthesia; Adult; Aged; Anesthesia, General; Buprenorphine; Cholecystectomy; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Regression Analysis; Time Factors

Topics: Adult; Aged; Anesthesia, Epidural; Buprenorphine; Cholecystectomy; Clinical Trials as Topic; Humans; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Vagotomy

Epidural buprenorphine was investigated as a postoperative analgesic in a randomized double-blind study of 158 patients given epidural analgesia with mepivacaine or bupivacaine for orthopedic surgery of the lower extremity. At the end of surgery, patients were given either 0.15 mg of epidural buprenorphine (n = 38), 0.3 mg (n = 37) in 15-ml saline, or no further epidural injections (n = 47, control group) after 2% mepivacaine for intraoperative anesthesia. A fourth group (n = 36) received 0.3 mg of buprenorphine in 15-ml saline, after the intraoperative use of 0.5% bupivacaine. The patients rated postoperative pain. The need for additional analgesics as well as side effects were recorded. Analgesia after 0.15 mg buprenorphine was superior to that after no reinjection for 6 hr after surgery (P less than 0.05). Buprenorphine (0.3 mg) was superior both to no reinjection and to 0.15 mg of buprenorphine until the twelfth hour (P less than 0.05). Analgesia after bupivacaine followed by 0.3 mg of buprenorphine was not significantly different than analgesia seen after mepivacaine followed by 0.3 mg of buprenorphine. There was an increase of PaCO2 of 2-5 mm Hg between 1.5-3.5 hr after 0.3 mg of buprenorphine without any evidence for late respiratory depression. Other side effects, e.g., disturbances of micturition, pruritus, nausea, vomiting, fatigue, and headache, were comparably common in all groups. The epidural administration of 0.3 mg buprenorphine may be recommended for postoperative analgesia following orthopedic surgery of the lower extremity.

Topics: Adult; Anesthesia, Epidural; Buprenorphine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Leg; Male; Mepivacaine; Middle Aged; Morphinans; Pain, Postoperative; Random Allocation

Topics: Adult; Aged; Buprenorphine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative

In a randomized double-blind-study nalbuphine 20 mg i.m. was compared with morphine 10 mg i.m. in 49 patients over the first 48 postoperative hours after hysterectomy. Nalbuphine proved to be a good analgetic, not statistically different from morphine but having statistically significantly fewer side effects.

Topics: Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hysterectomy; Middle Aged; Morphinans; Morphine; Nalbuphine; Pain, Postoperative; Random Allocation

Topics: Anesthesia, Epidural; Anesthesia, Intravenous; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Morphinans; Pain, Postoperative

Eighty fit adults having elective abdominal hysterectomy or cholecystectomy received buprenorphine or morphine intravenously at the start of peritoneal closure, in a randomised double-blind trial. The anaesthetic sequence precluded the use of other narcotic analgesics. Pain scores were lower in patients who received buprenorphine, as were the cumulative numbers of patients withdrawn from the trial at each interval because of pain, statistical significance being achieved at all intervals from one to seven hours after administration. Unexpectedly, patients having the upper abdominal procedure were more likely to receive satisfactory analgesia than those having abdominal hysterectomy. Vomiting occurred more commonly after buprenorphine, and mean respiratory rates were slightly lower. However, the differences were not statistically significant. One patient with protracted drowsiness and slow respiratory rate after buprenorphine received naloxone. No serious side-effects were noted. Buprenorphine 4-6 micrograms/kg provided adequate postoperative analgesia of greater duration than could be achieved with morphine, and the potency of buprenorphine when administered in this way was at least 33 times that of morphine.

Topics: Adolescent; Adult; Aged; Buprenorphine; Cholecystectomy; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hysterectomy; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Random Allocation; Respiration; Time Factors

In a prospective study, patients undergoing abdominal surgery were allocated randomly to receive intermittent morphine 10 mg i.m. (n = 41) or a single injection of buprenorphine 0.3 mg i.m. followed by sublingual buprenorphine 0.4 mg every 6 h (n = 39) for 3 days following operation. Patients receiving buprenorphine were allowed additional morphine, if required. Pain scores (linear analogue scale) in those patients receiving regular sublingual buprenorphine were consistently less than in those receiving intermittent morphine i.m. Half the patients receiving buprenorphine required no additional analgesia; only 15% required additional analgesia after the first day following operation. Arterial blood-gas analyses showed significant hypoxaemia and significantly greater carbon dioxide tensions in those receiving buprenorphine. These results suggest that a regimen based on the use of sublingual buprenorphine provides pain relief comparable to that provided by intermittent opiates i.m.

Topics: Abdomen; Administration, Oral; Buprenorphine; Carbon Dioxide; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Oxygen; Pain, Postoperative; Prospective Studies; Random Allocation; Tongue

40 Patients undergoing elective orthopaedic surgery of the lower limb randomly received either Buprenorphin sublingual (0,4 mg.) (Bsl) or Pentazocin i.m. (30 mg.) (Pim) for postoperative pain therapy. They were neither premedicated nor sedated. Analgesia was measured with a Visual Analogue Scale (VAS) and assessments by the anaesthetist and patient. Physiological measures were: Blood pressure, heart rate, arterial blood gases and serum cortisol. Side effects were registered. After Pim well known data were obtained: onset (10-30 min.) and duration (2 hours) of action and a significant pain reduction 20, 30 and 60 minutes after injection, whereas with Bsl onset was 60-120 min. and duration 6-7 hours of action and significant pain reduction was seen 120 and 180 min. after administration. 8 dropouts after Bsl up to 120 min. post applications are interpreted as a result of late onset or lack of analgesic action whereas the 13 drop outs 3 hours after Pim can be explained with the short lasting analgesic action of Pentazocin. Serum cortisol levels were better after Bsl, but did not correlate with the VAS. In Blood gas analyses, there were no group differences, especially no hypoxic or hypercapnic periods. There were no severe cardiocirculatory side effects, but significantly more hypertonic reactions and tachycardia after Pim. Other side effects were rare in both groups. The methods are discussed. Bsl has late onset but long duration of action with a higher efficacy than Pim. Bsl is strong and long acting. After an initial intravenous injection Bsl (0,4 mg.) should be administered at 6-hourly intervals.

Topics: Administration, Oral; Adolescent; Adult; Aged; Blood Pressure; Buprenorphine; Heart Rate; Humans; Hydrocortisone; Leg; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine

Sixty-nine patients undergoing upper and lower abdominal surgery were studied after operation to compare the analgesic effects of sublingual buprenorphine (0.4 mg) and slow release morphine sulphate tablets (MST, 20 mg) given 6 hourly in a double-blind, double-dummy trial. Both MST and buprenorphine produced satisfactory postoperative analgesia but the linear analogue pain scores were significantly lower on the second post operative day with MST.

Topics: Abdomen; Administration, Oral; Adult; Aged; Buprenorphine; Delayed-Action Preparations; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative

This study examined the analgesic effect, vital signs and side effects when 0.4 mg doses of buprenorphine were given pre-emptively for the treatment of postoperative pain after elective total hip replacement. Pain intensity, pain relief, retrospective peak pain intensity and pain relief, sedation, vital signs and side effects were measured 1 hour after surgery and then in the morning and evening of the first 2 postoperative days. There was a significant improvement in pain measured over the 3 days, with concomitant reduction in side effects and sedation. However, there was a significant increase in the number of patients with a pulse rate greater than 100 beats per minute. No particular benefit for postoperative pain relief was observed in patients receiving buprenorphine premedication in comparison with those who had received morphine or placebo.

Topics: Administration, Oral; Adult; Aged; Buprenorphine; Female; Hip Prosthesis; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Preanesthetic Medication; Time Factors

A double-blind comparison between buprenorphine and pentazocine was performed in 20 patients using an on demand analgesic system to provide analgesia after operation. The quality of analgesia, assessed subjectively, was good with both drugs and drug consumptions were compatible with previous potency estimates. The mean doses demanded in 24 h of buprenorphine (1.68 mg) and of pentazocine (382 mg) are consistent with those found in other trials although the between-patient variation was five- or six-fold. There was no significant difference in side-effects between the two groups. Buprenorphine and pentazocine may be used successfully in an on demand system to provide relief of severe pain after operation.

Topics: Adolescent; Adult; Aged; Buprenorphine; Cholecystectomy; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Infusions, Parenteral; Male; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine; Self Administration

In a controlled trial epidural buprenorphine was compared with epidural morphine as the sole means of analgesia after major abdominal surgery. Bolus injections of buprenorphine 60 micrograms in 10 ml or morphine 2 mg in 10 ml of normal saline were given on demand for the first 48 hours postoperatively. Both drugs produced significant reduction in pain scores as assessed by the linear visual analogue scale and both produced prolonged analgesia at this dosage, which could be extended by further 'top-ups'. The authors conclude that, for postoperative epidural analgesia, buprenorphine may be the opiate of choice and the reasons for this are discussed.

Topics: Adult; Buprenorphine; Clinical Trials as Topic; Epidural Space; Female; Humans; Injections; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Time Factors

Mr 1268 (alpha-5,9-dimethyl-2(3-methyl-3-methylfuryl)-2-hydroxy-6, 7-benzomorphan) was tested in two dosages (15 mg and 30 mg) at random on a total of 200 patients with severe postoperative pain in a double blind study against pentazocine and placebo. The analgesic effect of 30 mg Mr 1268 and 30 mg pentazocine compared with placebo was statistically significant 15 min after intramuscular injection. At the dosage applied no major respiratory or circulatory effects were observed in the patients. The minimal changes in the systolic blood pressure were of no statistical significance. Side-effects observed in many patients in the verum group were miosis and transpiration. For all other side-effects there was no statistically significant difference between placebo and the verum group or among the various verum groups.

Topics: Adult; Aged; Analgesics; Benzomorphans; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine; Placebos; Time Factors

A double-blind study was undertaken to compare nalbuphine, a synthetic partial agonist opiate, with meperidine in providing analgesia in patients following abdominal surgery, using the patient controlled analgesic technique. Both drugs showed a wide variation in demand requirements, but they were equally effective in relieving pain as assessed by the linear analogue technique. Neither drug caused a reduction of respiratory rate. The patient-controlled analgesic technique gave analgesia of good quality and it aided the comparison of the two drugs. However, some of the patients found the technique difficult to manage, and it is expensive and time-consuming. Until further experience is gained with this device its use should be confined to a constant care unit.

Topics: Adult; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Meperidine; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Self Administration

A randomized double-blind study was done to test the two opiates buprenorphine (0.3 mg i.v.) and pentazocine (30 mg i.v.) with regard to their applicability for the postoperative phase. These substances were chosen because they are not subject to drug prescription regulations. 60 patients who had undergone epigastric and hypogastric interventions under thiopental-sodium-induced halothane anesthesia received i.v. injections of one of the two analgetics as soon as they requested a pain-killer postoperatively. The subjective pain intensity registered by means of a visual analogue scale shows a gradual decrease after buprenorphine with maximal effects 1-3 h post injectionem (7.3 leads to 1.5). The duration of action is 8.2 +/- 0.7 h on the average (median 8 h; range 4-22 h). The maximal analgetic effect of pentazocine is already attained after 10 min (6.3 leads to 3.2). Thereafter the pain-intensity curve rises again. Pentazocine has a mean duration of action of 2.35 +/- 0.24 h (median 2 h; range 0.5-5 h). The inadequate analgetic effect of pentazocine manifests itself in an only slight initial reduction of the respiratory rate (19.5 leads to 17.5 min-1), which, on the other hand, decreases significantly and continuously under buprenorphine (20.8 leads to 13.5 min-1). Both substances cause increases of PaCO2 (buprenorphine 37.3 leads to 46.8 mmHg; pentazocine 36.3 leads to 43.0 mmHg), values greater than 50 mmHg being attained in individual cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adult; Aged; Buprenorphine; Carbon Dioxide; Clinical Trials as Topic; Double-Blind Method; Female; Hemodynamics; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine; Respiration; Time Factors

Two groups of 20 patients each were given immediately after hip-operation an epidural injection of 0,15 or 0,3 mg buprenorphine. Effects and side effects are compared with those observed in two groups of patients having the same type of operation, and given either 4 mg of morphine or saline (placebo) by epidural injection. Buprenorphine in both doses produced a shorter duration of analgesia than 4 mg of morphine. In no case did respiratory depression occur. Urinary retention after buprenorphine was barely more frequent than in the placebo group. Nausea and vomiting occurred in 35-45% of patients. We do not see an advantage in replacing morphine by buprenorphine for epidural opiate-analgesia, because the same high rate of nausea/vomiting is associated with a significantly shorter duration of analgesia after buprenorphine. We are convinced that epidural opiate-analgesia is most valuable for postoperative pain relief but should be reserved for selected cases.

Topics: Aged; Buprenorphine; Epidural Space; Hip Prosthesis; Humans; Injections; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative

Sixty patients undergoing day-case dental surgery were either given sublingual buprenorphine 0.2 mg or 0.4 mg or a buffered placebo 1 hour prior to general anaesthesia. Pre-operative anxiety was not allayed and there was no significant analgesia afforded by buprenorphine in the immediate postoperative period. The synthetic opiate depressed psychomotor function and both 0.2 mg and 0.4 mg buprenorphine yielded a significantly higher incidence of postoperative nausea and vomiting.

Topics: Adolescent; Adult; Ambulatory Surgical Procedures; Anesthesia, Dental; Anxiety; Blood Pressure; Buprenorphine; Drug Evaluation; Female; Heart Rate; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Preanesthetic Medication; Psychomotor Performance; Time Factors

Topics: Adult; Aged; Butorphanol; Clinical Trials as Topic; Double-Blind Method; Humans; Injections, Intramuscular; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine

Topics: Adult; Buprenorphine; Clinical Trials as Topic; Female; Genital Diseases, Female; Humans; Meperidine; Morphinans; Morphine; Pain, Postoperative

In a double-blind randomized non-crossover trial 47 patients received either morphine or buprenorphine by regular i.m. injection for 24 h after abdominal surgery. The two drugs were equally effective as analgesics at the doses used. Five in the buprenorphine group and none in the morphine group were excluded because of respiratory depression. Four of these had received opiates during operation. The remainder of the buprenorphine group developed progressively slower respiration rates after 12 h. The results indicate that buprenorphine has a synergistic respiratory depressant effect with fentanyl and phenoperidine and may have a cumulative effect when given regularly on a 6-hourly regimen.

Topics: Adolescent; Adult; Aged; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Random Allocation; Respiration

The analgesic activity of buprenorphine was monitored versus that of morphine in a double-blind, randomized, multiple-dose, parallel-design study involving 97 postsurgical patients. Patients could receive intramuscular injections of either buprenorphine (0.3, o.45, or 0.6 mg) or morphine (10, 15, or 20 mg) every 3 or more hours. Pain intensity, degree of sedation, vital signs, pain relief, and side effects were assessed prior to and at regular intervals after each drug injection. No statistically significant differences were found between the two drugs in total pain relief, sum of pain intensity difference by patient and over time, time to peak pain intensity difference, duration of pain, and side effects. It has been suggested that the addictive potential of buprenorphine may be less than that of morphine. Since both drugs seem to be effective analgesics, buprenorphine appears to offer an effective and safe alternative to morphine for patients with acute pain.

Topics: Adolescent; Adult; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Time Factors

The plasma concentrations and clinical effects of a single i.v. dose of buprenorphine 0.3 or 0.6 mg were studied in patients recovering from surgery. Analgesic and hormonal effects were greater with the greater dose without a parallel increase in respiratory depression. A comparison with previous work suggests that increased efficacy results either from the use of the larger dose or equivalently if the first required postoperative dose of 0.3 mg has been preceded by a similar loading dose.

Topics: Aged; Blood Glucose; Buprenorphine; Female; Humans; Hydrocortisone; Injections, Intravenous; Male; Middle Aged; Morphinans; Pain, Postoperative; Respiration

In 51 patients undergoing elective abdominal surgery, analgesia was provided for the first 24 h after surgery by bolus injections of buprenorphine 0.1 or 0.2 mg given i.v. on patient demand using a patient-operated syringe driver (the "Cardiff" palliator). Excellent analgesia was reported by 47 patients. Four elderly patients had difficulty in operating the demand apparatus. In two other patients, clinically significant ventilatory depression necessitated abandoning the trial. Although there was a high degree of patient and staff acceptance of the method, the potential for ventilatory depression emphasizes the need for close observation of patients receiving i.v. opioids by this technique.

Topics: Adult; Aged; Buprenorphine; Hemodynamics; Humans; Injections, Intravenous; Middle Aged; Morphinans; Pain, Postoperative; Respiration; Self Administration; Time Factors

One hundred and twenty-six patients undergoing upper and lower abdominal surgery were studied after operation to compare the analgesic effects of i.m. morphine, sublingual buprenorphine and self-administered i.v. pethidine by Cardiff Palliator. There were no significant differences between analgesic regimens in respect of subjective linear analogue pain scores or static and dynamic lung volumes assessed at 24 and 48 h after operation and 5 days after operation in patients who underwent upper abdominal surgery. Sublingual buprenorphine produced more nausea and sedation than the other two treatments, but the differences were not clinically important. However, it offered considerable advantages in terms of ease of administration.

Topics: Administration, Oral; Adolescent; Adult; Aged; Buprenorphine; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Male; Meperidine; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Respiratory Function Tests; Self Administration; Tongue

1 A 10 h study of plasma drug concentrations of the opiate buprenorphine after use was designed because a previous 3 h study had shown that peak plasma drug concentrations in some patients had not occurred by 3 h after the sublingual dose. 2 Fifteen postoperative patients were studied: at 3 h after a 0.3 mg intravenous dose five patients received a sublingual preparation of 0.4 mg of buprenorphine, five 0.8 mg of buprenorphine and five placebo. Plasma drug concentrations of buprenorphine were measured by specific radioimmuno-assay. 3 Plasma drug concentrations after sublingual buprenorphine were significantly higher than those in the placebo group by 1 h. They remained significantly higher over the succeeding nine hours. The mean time to peak plasma drug concentration was about 200 min in both the 0.4 mg and 0.8 mg groups (range 90-360 min). The plasma drug concentrations in the 0.8 mg group were approximately twice those in the 0.4 mg group; the ratio of the relative systemic availabilities was similarly 1.8:1. The absolute systemic availability was estimated at about 55% for both groups. Uptake of buprenorphine from the sublingual site was essentially complete by 5 h after the dose was given. 4 The implications for the timing of sublingual doses in clinical use are discussed.

Topics: Aged; Biological Availability; Buprenorphine; Female; Humans; Kinetics; Male; Middle Aged; Models, Biological; Morphinans; Pain, Postoperative; Time Factors; Tongue

In a double-blind study using patients' subjective reports as indices of analgesia, the relative analgesic potency of intramuscular and oral nalbuphine was determined in 104 postoperative patients. Effects of single doses of 3 and 9 mg of intramuscular nalbuphine were compared with those of 15- and 45-mg oral doses of nalbuphine by means of a parallel study design (26 patients per treatment group). When both intensity and duration of analgesia are considered (i.e., total analgesic effect), oral nalbuphine is 1/4 to 1/5 as potent as intramuscular nalbuphine. In terms of peak effect, however, oral nalbuphine is only 1/10 as potent. The oral/parenteral potency ratio for total effect is close to those obtained by Houde et al. in studies of morphine (1/6), metopon (1/5), hydromorphone (1/5), and oxymorphone (1/6) and suggests that oral nalbuphine undergoes substantial biotransformation on first pass through gut mucosa and liver. Since intramuscular nalbuphine is approximately equipotent to morphine, it should be feasible to equal the analgesia induced by the usual intramuscular doses of morphine with reasonable oral doses of nalbuphine. Although nalbuphine is a mixed agonist/antagonist analgesic, no psychotomimetic reactions were observed.

Topics: Administration, Oral; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Injections, Intramuscular; Morphinans; Nalbuphine; Pain, Postoperative; Time Factors

Morphine (5 mg) and buprenorphine (0.15 mg) given by the epidural route were compared in 50 patients recovering from abdominal surgery. Pain relief score, sedation score and clinical measures were evaluated in a double-blind study. Both substances produced thorough analgesia with short latency (2-6 min) of long duration (8-9 h). Side effects were encountered in some morphine cases only, but never therapy had to be discontinued. Total lack of side effects with buprenorphine favours its application in epidural pain relief.

Topics: Anesthesia, Epidural; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Female; Hemodynamics; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Random Allocation

1 An oral combination of buprenorphine and paracetamol was compared with paracetamol alone in a single dose, double-blind postoperative study. One hundred and twenty patients undergoing elective minor orthopaedic operations were allocated to four groups of 30 patients. The four treatments were 1,1.5 or 2 mg of buprenorphine with paracetamol 1,000 mg or paracetamol 1,000 mg alone. 2 There were no significant differences between the groups in analgesia measured by the observer over the 6 h period of direct observations. The oral opiate produced a significant increase in duration of analgesia beyond the 6 h study period. A significant increase in side-effects was seen only at the highest buprenorphine dose compared with paracetamol. 3 The problems of trial design for analgesic combinations are considered. Drug mixtures create additional complexities which decrease the certainty of the conclusion that no real benefits result from such mixtures.

Topics: Acetaminophen; Adult; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Female; Humans; Male; Morphinans; Pain, Postoperative

Ninety-eight patients completed a double-blind, multidose, randomized parallel study in which buprenorphine (Temgesic) was compared to morphine. Drugs were administered at approximately equipotent intramuscular doses for a maximum of three days for the relief of moderate to severe postoperative pain. The two drugs exhibited similar profiles with pain relief evident at 1/2 hour, peaking at 1 hour, and decreasing to slight relief at 4-5 hours, with no significant differences for time to remedication. The most frequent side effect was somnolence. One patient suffered sudden chest pain shortly after an injection of morphine, and one patient had moderate hypoventilation after buprenorphine; both patients recovered uneventfully. Overall, both drugs provided good or excellent analgesia in 80 per cent of the patients in this unique multidose/observational study. Thus, these data and the reported lack of withdrawal symptoms and the absence of physical dependence liability suggest that buprenorphine may have a role in the management of chronic pain.

Topics: Adult; Buprenorphine; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Morphinans; Morphine; Pain, Postoperative; Random Allocation

Topics: Adolescent; Adult; Aged; Buprenorphine; Female; Humans; Male; Meperidine; Middle Aged; Morphinans; Pain, Postoperative; Tramadol

The effect of sublingual buprenorphine (0.4 mg) was compared with that of oral dihydrocodeine (60 mg) in patients experiencing post-operative pain following general surgery. Pain relief was significantly greater for buprenorphine than for dihydrocodeine, based on both peak effect and total effect. Both treatments were effective from 30 minutes. There was evidence that buprenorphine and a slightly slower onset of action, but a distinctly longer duration of action, than dihydrocodeine. Unwanted effects were similar for both treatments.

Topics: Administration, Oral; Buprenorphine; Codeine; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Random Allocation

Analgesic effects as well as side effects, circulatory and respiratory parameters of 0.3 mg Buprenorphine (Temgesic) were compared to 10 mg Nicomorphine (Vilan) intramuscularly injected in a double-blind, randomized study for the relief of postoperative pain. Buprenorphine produced an equally potent but longer acting analgesic effect compared to Nicomorphine, although slight delayed. There were only few and slight side effects and no influence on the circulation and the respiration. In the search for a new long-acting and strong analgesic Buprenorphine proved to be superior to Nicomorphine in the control of postoperative pain.

Topics: Adult; Buprenorphine; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Morphinans; Morphine Derivatives; Nicotinic Acids; Pain, Postoperative

Analgesic effects as well as side effects, circulatory and respiratory parameters of 50 mg tramadol (Tramal) were compared with 0.3 mg buprenorphine (Temgesic) in a doubleblind, randomized study for the relief of postoperative pain. Buprenorphine produced a more potent and longer acting analgesic effect compared to tramadol, although slightly delayed. There were only few and slight side effects and no influence on the circulation and respiration. In the search for a new long-acting and strong analgesic Tramadol proved to be unable to replace buprenorphine in the control of postoperative pain.

Topics: Adult; Blood Pressure; Buprenorphine; Cyclohexanols; Double-Blind Method; Humans; Middle Aged; Morphinans; Pain, Postoperative; Postoperative Period; Pulse; Respiration; Time Factors; Tramadol

Topics: Adult; Aged; Butorphanol; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative

Topics: Adult; Butorphanol; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hysterectomy; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine

Twenty-five women were investigated on the day after lower abdominal surgery in a single-blind non-cross-over trial to assess and compare the haemodynamic effects of intravenous injections of buprenorphine 0.3 mg and morphine 7.5 mg. Arterial blood pressure was measured by sphygmomanometry and cardiac output by thoracic impedance cardiography. Arterial blood pressure was significantly reduced following both drugs (p < 0.05), although the mean decrease in systolic arterial pressure was less than 8 mmHg. However, in one patient in each group the decrease was more than 20 mmHg. Cardiac output decreased but the mean reduction was less than 5%. The greatest individual decreases were 21% after buprenorphine and 30% after morphine. Myocardial contractility, assessed by systolic time indices, did not appear to change. There were no consistent differences in the haemodynamic effects of the two drugs.

Topics: Abdomen; Adult; Buprenorphine; Clinical Trials as Topic; Female; Hemodynamics; Humans; Injections, Intravenous; Middle Aged; Morphinans; Morphine; Pain, Postoperative

The analgesic profile and side-effects of buprenorphine 0.3 mg and morphine 10 mg intramuscularly were compared postoperatively in a double-blind, non-crossover, multiple-dose study. When the patient complained of moderate to severe postoperative pain after halothane-relaxant anesthesia for upper abdominal surgery, the first test dose of either drug was given. Subsequent similar doses of buprenorphine 0.3 mg or morphine 10 mg were given when required (maximum ten doses). The first dose of both drugs gave an equal decrease in pain intensity, suggesting a relative potency of 33:1 for both buprenorphine/morphine. A mean of 0.51 mg buprenorphine or 17 mg morphine had to be administered for satisfactory initial analgesia. Thereafter, the next analgesic dose was required a mean of 10.3 h after buprenorphine compared to 5.9 h after morphine (P less than 0.01). Significantly (P less than 0.01) fewer analgesic doses (mean 5.6) were needed in the buprenorphine group within the first 48 h postoperatively as compared to the morphine group (mean 7.3). A more pronounced mean decrease in the respiratory rate was observed after buprenorphine, but the mean minimum respiratory rates did not differ significantly from each other. Other effects of the two drugs on vital signs were similar. The incidence of other side-effects was fairly similar after both analgesics. The patients' subjective appraisal favoured buprenorphine.

Topics: Adolescent; Adult; Aged; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Random Allocation; Time Factors

One hundred four patients with moderate to severe postoperative pain participated in a double-blind study comparing butorphanol/acetaminophen with oxycodone/acetaminophen and placebo with respect to analgesic effectiveness and incidence of side effects. Pain was rated by the patients and an observer; sums of these data were calculated. Side effects, their severity and their relationship to the drug were recorded. Both active medications provided statistically significant levels of analgesia as compared with placebo. Analgesia produced by both combinations of drugs was statistically similar until 4 hours postdrug. From 4 to 6 hours postdrug, butorphanol/acetaminophen was significantly more analgesic. Both active medications produced analgesia within 0.5 hours, showing a peak effect at 1 to 2 hours and lasting for 6 hours. The incidence of side effects was minimal and statistically equivalent for each treatment group.

Topics: Acetaminophen; Administration, Oral; Adult; Aged; Analgesics; Butorphanol; Codeine; Double-Blind Method; Drug Combinations; Drug Evaluation; Female; Hospitalization; Humans; Male; Middle Aged; Morphinans; Oxycodone; Pain, Postoperative

Sixty patients with moderate or severe postsurgical pain were randomly divided into three equal groups for a double-blind comparison of the analgesic effectiveness of intramuscular butorphanol (2 and 4 mg) and pentazocine (60 mg). The groups were demographically similar. Pain intensity and pain relief were scored at 10, 20, 30, 60, 120, 180, and 240 minutes after administration of the drug. All treatments provided significant analgesic activity (P less than .05) within ten minutes. However, both doses of butorphanol reached their peak effect at 30 minutes, in contrast to 60 minutes for pentazocine. The duration of effect appeared somewhat longer for butorphanol, though this did not achieve statistical significance. Butorphanol (4 mg) had a significantly greater (P less than .05) analgesic effect at ten minutes than pentazocine (60 mg), and both butorphanol treatments (2 and 4 mg) were significantly better than pentazocine, according to many parameters at 20 and 30 minutes. Side effects, chiefly sleepiness and dizziness, were seen in 15% of the patients, with no significant difference between the treatment groups.

Topics: Adolescent; Adult; Aged; Butorphanol; Clinical Trials as Topic; Dizziness; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine; Sleep

In a double-blind study of on-demand intravenous analgesia buprenorphine was found to be about 600 times as potent as pethidine. The incidence of side effects was similar with both drugs. The quality of analgesia, subjectively assessed, was good with both drugs using this method of administration. Provided that its low potential for abuse is substantiated, buprenorphine appears to be a powerful analgesic that may successfully be given intravenously on demand.

Topics: Adolescent; Adult; Aged; Buprenorphine; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Humans; Injections, Intravenous; Meperidine; Middle Aged; Morphinans; Pain, Postoperative

Topics: Adult; Aged; Butorphanol; Clinical Trials as Topic; Codeine; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Time Factors

An oral butorphanol/acetaminophen (4 mg/650 mg) combination product was evaluated for analgesic activity in 120 postoperative patients employing a double-blind experimental design. The combination product was significantly (p less than 0.05) superior to either butorphanol (4 mg) or acetaminophen (650 mg) as well as placebo. Except for acetaminophen which was only significantly different (p less than 0.05) from placebo at 2 hours according to pain relief, all other treatments were superior to placebo over the entire 4 hour observation period. The data demonstrate that butorphanol and acetaminophen have at least additive analgesic activity with a suggestion of synergism. A single tablet dose of the combination product (butorphanol 2 mg/acetaminophen 325 mg) was evaluated in a second study involving 60 patients and was significantly (p less than 0.05) superior to placebo. Both studies demonstrate that the butorphanol/acetaminophen combination product has potent analgesic activity with a minimal side effect profile.

Topics: Acetaminophen; Administration, Oral; Adolescent; Adult; Aged; Analgesics; Butorphanol; Child; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Placebos

The analgesic effects of sublingually administered buprenorphine 0.4 mg have been compared with morphine 10 mg given intramuscularly in patients following operation. The results indicate a slower onset of action for buprenorphine but of much longer duration than morphine. There were no serious side effects or difference in their incidence between the two drugs.

Topics: Administration, Oral; Adult; Buprenorphine; Drug Evaluation; Humans; Morphinans; Morphine; Mouth Floor; Pain, Postoperative

In a double-study, using patients' subjective reports as indices of analgesia, the relative analgesic potency of intramuscular nalbuphine and morphine was determined in 56 postoperative patients. A total of 28 crossover comparisons (utilizing the twin passover, balanced four-point incomplete block design) were performed in two sequentially related experiments, each assay comparing 4 and 8 mg of morphine with either 3 and 6 or 6 and 12 mg of nalbuphine. When both intensity and duration of analgesia are considered (i.e., total analgesic effect), nalbuphine was 0.8 to 0.9 times as potent as morphine. In terms of peak analgesic effect, nalbuphine was 0.7 to 0.8 times as potent. Both the time-effect curves and the relative potency estimates suggest that nalbuphine has a slightly longer duration of action than morphine at doses that are equianalgesic in terms of peak effect. Side effects of the type usually noted after the administration of potent injectable analgesics to postoperative patients were observed after both morphine and nalbuphine. Although nalbuphine is a potent narcotic antagonist, no psychotomimetic reactions were observed.

Topics: Adult; Analgesics; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Morphine; Nalbuphine; Pain, Postoperative; Research Design; Time Factors

A double-blind, between-patient comparison has been made of the effects of morphine 10 mg i.v. and buprenorphine 0.3 mg i.v. on the prevention of pain after operation. The drugs were given by the anaesthetist at the end of the operation, and the onset and severity of pain were assessed by a trained nurse. Both drugs caused a significant delay in the appearance of severe pain when compared with the control group, but with buprenorphine the mean delay of 10.5 h was more than twice that of morphine. The only side-effect to occur more frequently after administration of the analgesics was drowsiness, the incidence being greater after buprenorphine than after morphine.

Topics: Adult; Aged; Analgesics; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Sleep Stages

Topics: Butorphanol; Clinical Trials as Topic; Double-Blind Method; Humans; Meperidine; Morphinans; Pain, Postoperative

A comparison was made of the relief of pain after operation, obtained following the i.v. administration of buprenophrine and pethidine in 60 patients with lower abdominal incisions. No difference could be detected between the maximum analgesia produced by eigher drug, but analgesia following buprenorphine appeared to last about four times as long as that following pethidine. When the drugs were compared on a "dose per body weight" basis the results supported a ratio of potency in the order of 1 : 200 in favour of buprenorphine. Vomiting, drowsiness and dizziness were less frequent following buprenorphine, but a similar frequency of nausea was observed with both agents. Marked miosis occurred 5--10 min after the i.v. injection of buprenorphine, but no serious side-effects were observed with either drug. The i.v. injection of buprenorphine, but no serious side-effects were observed with either drug. The i.v. administration of buprenorphine appeared to be effective in the management of pain after operation in patients with lower abdominal incisions.

Topics: Adult; Aged; Analgesics; Female; Humans; Injections, Intravenous; Meperidine; Middle Aged; Morphinans; Pain, Postoperative; Time Factors

Intravenous doses of butorphanol tartrate (0.5 mg, 1.0 mg and 2.0 mg) and meperidine hydrochloride (20 mg and 40 mg) were compared under controlled conditions employing a double blind study design. Informed consent was obtained from all post-operative patients suffering from moderate to severe pain who participated in this study. Approximately 25 patients were included in each group. The data from 125 patients were subjected to statistical analysis. The results indicated that butorphanol is approximately 40 to 50 times more potent than meperidine. In addition, at most of the time intervals, there were no statistically significant differences between the responses to butorphanol 0.5 mg and 1 mg and meperidine 20 mg and 40 mg; but the response to butorphanol 2 mg was significantly (p less than 0.05) better than the low dose of each agent. The low doses of butorphanol (0.5 mg) and meperidine (20 mg) appear to have an effective duration of action of less than two hours. The larger doses (butorphanol 1.0 mg and 2.0 mg and meperidine 40 mg) appeared to produce a two- to four-hour duration of action. The largest butorphanol dose (2.0 mg) appeared to produce the longest duration of action. A comparison of the test groups with respect to the incidence and type of side effects showed that butorphanol 2.0 mg produced a greater incidence of drowsiness (39 per cent). The overall incidence of drowsiness for patients receiving either the 0.5 mg or 1.0 mg dose of butorphanol was 12 per cent, as compared with an 8 per cent overall incidence in the meperidine group. The incidence of other side effects was relatively low in all test groups. No significant differences were noted among the groups with regard to the onset (usually less than or equal to 30 minutes post-therapy) or the duration (usually less than or equal to 2 hours) of side effects. Butorphanol appears to be a safe and effective analgesic for the relief of moderate to severe post-operative pain.

Topics: Adult; Aged; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Male; Meperidine; Middle Aged; Morphinans; Pain, Postoperative; Time Factors

One hundred patients, who were in pain during the immediate postoperative period after upper abdominal operations, were included in this double-blind, between-patient, two-dose study. During N2O-O2-halothane-relaxant anaesthesia no analgesics were given. The patients received 0.07 mg/kg or 0.14 mg/kg of nalbuphine or 0.3 mg/kg or 0.6 mg/kg of pentazocine by intravenous injection. Pain and side effects were assessed for 4 h after administration of the test drug, or until the pain returned to the pre-injection level, when a conventional analgesic was given. The onset of pain relief was similar and the peak effect occurred about half an hour after the injection after both drugs. On a milligram basis, nalbuphine seemed to be about three times as potent as pentazocine. The duration of action seemed to be slightly longer after nalbuphine, but 2 1/2 hrs. after the injection the pain had returned to preinjection level in 2/3 of the patients, even after the higher doses of both drugs. Except for sleepiness, there were few side effects and they were similar after both drugs. No psychotomimetic effects were observed.

Topics: Adult; Aged; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Pentazocine

A new thebaine derivative, buprenorphine, 0.6 mg, was compared with morphine 15 mg in a double-blind trial, in patients recovering from elective Caesarean section. Within 1 h of administration analgesia was obtained with both drugs and was sustained for 7-8 h with buprenorphine, and 3-4 h with morphine. Buprenorphine caused a greater decrease in diastolic arterial pressure than did morphine, but arterial systolic pressure and heart rate were not influenced by either drug. No serious side-effects were encountered in this study.

Topics: Cesarean Section; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Morphinans; Morphine; Pain, Postoperative; Pregnancy; Respiration

The analgesic effects of buprenorphine 2 microgram/kg--1 and 8 microgram. kg--1 were compared with those of pethidine 1 mg. kg--1 and pentazocine 0.6 mg.kg--1 in 172 patients recovering from surgery. The drugs were given by i.m. injection in the period immediately after operation and the quality of pain relief was assessed at intervals for at least 4h. Buprenorphine 4-8 microgram-kg-1 was shown to be an effective analgesic, superior in some cases to the other drugs in the doses employed in the study.

Topics: Adult; Aged; Analgesics; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Male; Meperidine; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine

In a comparative trial, buprenorphine 0-3 mg or morphine 10 mg was administered intramuscularly to patients post-operatively. The new drug buprenorphine produced more pain relief than morphine and appeared to have a longer duration of action. The side-effects produced by the two drugs were similar, as were the effect on respiratory and cardiovascular measurements.

Topics: Analgesics; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Humans; Morphinans; Morphine; Pain, Postoperative

A double-blind, randomized trial was conducted in 120 post-surgical patients to evaluate the oral analgesic activity of butorphanol tartrate (4 mg and 8 mg) and pentazocine HCl (50 mg) as compared to placebo. Both dose of butorphanol as well as pentazocine proved to be significantly (p less than 0-05) more effective than placebo. Butorphanol 4 mg and pentazocine 50 mg were never significantly different from each other, while butorphanol 8 mg was significantly beeter than both butorphanol 4 mg as well as pentazocine 50 mg in several instances, demonstrating a significant dose effect relationship for butorphanol. All of the active treatment provided maximum pain relief within 1 to 2 hours and were effective over 4 hours. In contrast to the other treatments, none of the 8 mg butorphanol patients required remedication during the 4-hour observation period. Generally, the incidence fo side-effects appeared low.

Topics: Adolescent; Adult; Aged; Analgesics; Clinical Trials as Topic; Double-Blind Method; Drug Evaluation; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine; Placebos

The analgesic effects of R & S 218-M, administered in doses of 0.56 mg/70 kg and 0.35 mg/70 kg, were compared with those of morphine sulphate 10.5 mg/70 kg for the relief of abdominal pain following surgery in healthy adults. The drugs were given as the first potent analgesic after operation and the subjects were interviewed at 30-min intervals until the pain became severe again. All the interviews were conducted by the one observer. R & S 218-M 0.56 mg/70 kg was as effective as morphine sulfate 10.5 mg/70 kg, while R & S 218-M 0.35 mg/70 kg was inferior. No evidence was found to support the claim that R & S 218-M causes less respiratory depression when compared with morphine sulphate.

Topics: Abdomen; Adolescent; Adult; Allyl Compounds; Blood Pressure; Clinical Trials as Topic; Etorphine; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Pulse; Respiration

Butorphanol, 1, 2, and 4 mg/70 kg, and meperidine, 40 and 80 mg/70 kg, were compared for analgesic activity and side effects in 104 hospitalized postoperative patients. Butorphanol proved to be 30 to 40 times as potent as meperidine on a weight basis. Both medications provided maximum pain relief approximately 1 hr after administration. The most common side effect in all groups was drowsiness.

Topics: Adult; Aged; Analgesics; Clinical Trials as Topic; Female; Humans; Injections, Intramuscular; Male; Meperidine; Middle Aged; Morphinans; Pain, Postoperative

A double-blind, randomized trial was conducted with 124 post-operative patients to compare the analgesic activity and possible side-effects of a new synthetic analgesic--butorphanol tartrate (1, 2, and 4 mg)--and pentazocine lactate (30 and 60 mg), adminstered intramuscularly. Butorphanol was determined to be 16 times more potent than pentazocine, on a weight basis. Both medications provided maximum pain relief within one hour after administration, and had comparable durations of action. Drowsiness was the most common side-effect, and it appeared to be dose related in all test groups.

Topics: Adult; Aged; Analgesics; Clinical Trials as Topic; Fatigue; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine

In 150 patients buprenorphine was given as postoperative analgesic in a dose of 4 microgram/kg. Pain suppression was judged very good (71%), fairly good (24%) and insufficient (5%). Analgesic activity lasted at least 325 +/- 15 min. Side effects were few.

Topics: Adult; Aged; Analgesics; Clinical Trials as Topic; Drug Evaluation; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative

Topics: Adolescent; Adult; Aged; Analgesics; Clinical Trials as Topic; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Time Factors

Either butorphanol tartrate (1, 2, or 4 mg) or pentazocine (30 or 60 mg) was given intramuscularly (5 dose groups) to 262 patients, who were scheduled for major operations, if they had severe pain after full awakening in the recovery room, postoperatively under double-blind conditions. There were at least 50 patients in each of the five dosage groups. Pain intensity and relief were scored numerically for each treated patient at 1/2 1, 2, 3 and 4 hr, while under direct surveillance, and the patients were seen again for follow-ups during the first 24 hr postoperatively. Appreciable pain relief developed within 30 min at all dose levels, with a peak analgesic effect apparent at about 1 hr. Satisfactory relief persisted for 4 hr in the majority of patients in each group. With the lowest dose of butorphanol tartrate (1 mg), which gave good pain relief for only 2 to 4 hr, approximately 60% of the patients had to be remedicated within 4 hr. Vital signs were not appreciably affected, but the patients who received the high dose of analgesics (butorphanol tartrate 4 mg or pentazocine lactate 60 mg) were often quite drowsy. The incidence of other side effects was negligible. The relative potency assay showed that butorphanol was approximately 20 times as potent as pentazocine for up to 4 hr.

Topics: Adolescent; Adult; Aged; Analgesics; Clinical Trials as Topic; Cyclobutanes; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine; Time Factors

Topics: Anesthesia, Inhalation; Atropine; Clinical Trials as Topic; Cyclobutanes; Diazepam; Dose-Response Relationship, Drug; Enflurane; Female; Halothane; Humans; Hydroxyzine; Injections, Intramuscular; Male; Morphinans; Morphine; Nitrous Oxide; Pain, Postoperative; Preanesthetic Medication; Time Factors

Sinomenine, a major bioactive ingredient isolated from traditional Chinese medicine Sinomenium acutum, has been reported to have analgesic effects in various pain animal models. N-demethylsinomenine, the N-demethylated product of sinomenine, has been identified to be the major metabolite of sinomenine and is also a natural component extracted from Sinomenium acutum. This study examined the anti-allodynic effects of N-demethylsinomenine in a mouse model of postoperative pain. A significant and sustained mechanical allodynia that lasted for 4 days was induced by making a surgical incision on the right hind paw in mice. Acute treatment with N-demethylsinomenine (10-40 mg/kg, s.c.) relieved the mechanical allodynia in a dose-dependent manner. Although there was no difference in maximal analgesic effect between N-demethylsinomenine (40 mg/kg, s.c.) and sinomenine (40 mg/kg, s.c.), the onset of action of N-demethylsinomenine was quicker than sinomenine. Repeated treatment with N-demethylsinomenine (10-40 mg/kg/day, s.c.) also dose-dependently exerted sustained antinociception against postoperative allodynia and did not produce analgesic tolerance and carry-over effect. The anti-allodynia induced by N-demethylsinomenine (40 mg/kg, s.c.) was attenuated by bicuculline, a selective γ-aminobutyric acid type A (GABA

Topics: Analgesics; Animals; Bicuculline; Disease Models, Animal; Dose-Response Relationship, Drug; GABA-A Receptor Antagonists; Hyperalgesia; Male; Mice; Mice, Inbred ICR; Morphinans; Pain, Postoperative; Receptors, GABA-A

This study examined the antinociceptive effects of sinomenine in a rat model of postoperative pain.. Male and female rats were subjected to a surgical incision in the right hind paw, and the von Frey filament test was used to measure mechanical hypersensitivity after drug or vehicle treatment (p.o. or i.p.). Rats were treated daily with sinomenine before or after the surgery and the AUCs of the antinociceptive effects measured during a 4 h period were calculated to determine the ED50 values of sinomenine. The anti-hyperalgesic effects of different doses of a combination of sinomenine and acetaminophen (paracetamol) were assessed in another group of rats. Dose combinations were determined by using a fixed ratio dose-addition analysis method.. Sinomenine (5-80 mg·kg(-1) ) produced dose-dependent antinociceptive effects in rats that had been subjected to surgery and this effect lasted for 4 h. The potency of sinomenine, given i.p. or p.o., did not differ between male and female rats. However, sinomenine was fourfold more potent when given i.p. than p.o. The GABAA receptor antagonist bicuculline blocked the antinociceptive effects of sinomenine. The antinociceptive effect of a daily treatment with sinomenine remained stable throughout the course of postoperative pain. Pretreatment with sinomenine did not alter the mechanical hypersensitivity post-surgery. The combination of sinomenine with acetaminophen produced an infra-additive interaction.. Sinomenine demonstrated significant antinociceptive activity against postoperative pain and may be a useful novel pharmacotherapy for the management of postoperative pain.

Topics: Acetaminophen; Analgesics; Animals; Dose-Response Relationship, Drug; Female; Male; Morphinans; Pain, Postoperative; Rats; Rats, Sprague-Dawley

To observe the clinical effect and experimental result of long-acting analgesic in the treatment of anorectal post-operational pain.. Analysing the pathological features of anorectal post-operational pain, and select the Radix Stephana Tetrandra, which could disperse pathogenic Wind and dampness, relieve spasm and pain, as the major component. The authors extracted Sinomenine from the Stephana and by mixing with methylene blue and bupivacaine hydrochloride, an injection was prepared. Three groups were in the clinical observation: Long-acting analgesic group (102 cases), routine treatment group (80 cases) and the control group treated by Tramal (30 cases). The curative effect was observed and animal experiment was conducted.. The total analgesic rate of the long-acting analgesia was 56.86%. The clinical effect was better than using Bupivacaini hydrochloride or Tramal alone (P < 0.05). It was shown in experiment that long-acting analgesic had obvious effects of topical analgesic and muscle relaxant.. Long-acting analgesic has significant effect in relieving the anorectal post-operational pain.

Topics: Adult; Aged; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Drugs, Chinese Herbal; Female; Fissure in Ano; Hemorrhoids; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative

The analgesic nalbuphine was tested in Czechoslovakia in three departments of anaesthesiology. On 94 patients during the first 24 postoperative hours 43.3% of the patients were sufficiently treated with one injection of 10 mg nalbuphine, 30% needed two injections, 20% three injections and 6.7% four injections. The average duration of the analgesic effect was about 4 hours. Repeated injections achieved prolonged action. Side-effects occurred less frequently with nalbuphine than with morphine. It was shown that it is important in the postoperative period to start with the analgetic therapy before pain occurs.

Topics: Female; Humans; Male; Morphinans; Nalbuphine; Pain, Postoperative

The optimum doses according to age of butorphanol tartrate as a supplemental drug during epidural and spinal anesthesia were investigated in 60 patients without complications. We classified patients into 4 groups by age as A, B, C and D-group. A-group consisting of patients between 20 to 40 years received 1.5mg of butorphanol. B-group 41-60, C-group 61-75 and D-group over 76 years received 1.0mg, 0.5mg and 0.25mg respectively. After operation was started without pain, and during the stable period, we determined by age, doses of butorphanol injected intravenously in one minute. HRs, mean BPs, respiratory rates (RRs) and so on were obtained at the preinjection point and 5 minutes after injection. In addition, in 15 patients, arterial blood gas analysis was performed at the same times. Butorphanol injections decreased HRs, mean BPs and RRs significantly. But there was no one whose PaCO2 increased more than 50 mmHg and no difference was found in degree of side effects between the groups. In conclusion, this study suggests that the decision to administer doses depending on the age is useful to decrease frequency of the grave side effects, especially respiratory depression which the elderly people frequently fall into.

Topics: Adult; Aged; Aged, 80 and over; Anesthesia, Conduction; Butorphanol; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphinans; Pain, Postoperative

Nalbuphine and nicomorphine were administered intramusculary in single doses for the relief of moderate to severe pain after abdominal surgery in a group of 40 patients to compare the analgesic effect and clinical tolerance during a 2 hour period. There was no statistically significant difference of the analgesic effect. In both groups SBP, DBP and RR decreased and HR increased significantly after injection but the tolerance of nalbuphine seems to be beter. Nalbuphine is a good choice for postoperative pain.

Topics: Adult; Aged; Blood Pressure; Female; Heart Rate; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Morphine Derivatives; Nalbuphine; Nicotinic Acids; Pain, Postoperative; Respiration

1. Activity of the mimetic muscles of the upper face were recorded from awake and anesthetized patients by surface electromyography (SEMG). 2. High amplitude SEMG accompanied ketamine anesthesia and/or the presentation of pain-provoking stimuli. 3. During periods of elevated facial muscle activity, fentanyl or butorphanol decreased SEMG amplitude. 4. The opioid-induced SEMG depression was not consistently associated with either lowered vigilance or analgesia but did provide an objective measure of drug effect.

Topics: Adult; Aged; Butorphanol; Electromyography; Evoked Potentials; Facial Muscles; Fentanyl; Humans; Middle Aged; Morphinans; Naloxone; Pain; Pain, Postoperative; Succinylcholine

Topics: Adult; Aged; Double-Blind Method; Drug Evaluation; Drug Therapy, Combination; Female; Humans; Injections, Spinal; Male; Middle Aged; Morphinans; Morphine; Nalbuphine; Pain, Postoperative

Patient-controlled analgesia (PCA) has been studied extensively for the treatment of postoperative pain using narcotic analgesics. Butorphanol, a nonnarcotic injectable analgesic, has not previously been investigated using this drug delivery mechanism. Twenty-five patients undergoing general abdominal surgery and general anesthesia used a PCA device with butorphanol as the analgesic agent. Most patients (84%) were able to obtain excellent postoperative pain relief. The role of butorphanol in the management of postoperative pain should be expanded to include patient-controlled drug delivery.

Topics: Adult; Aged; Butorphanol; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Morphinans; Pain Measurement; Pain, Postoperative; Self Administration

Topics: Butorphanol; Humans; Injections, Epidural; Morphinans; Pain, Postoperative

Topics: Child; Child, Preschool; Humans; Morphinans; Nalbuphine; Pain, Postoperative; Tonsillectomy

Endocrine and hemodynamic changes associated with the antagonism of fentanyl by nalbuphine have not been reported. Therefore, the authors studied ten patients after anesthetic induction with thiopental, fentanyl, tracheal intubation aided by succinylcholine and maintenance with diazepam, pancuronium, N2O, and further doses of fentanyl. Eight of the patients underwent cholecystectomy, one had a hysterectomy, and another had an abdominoplasty. After reversal of neuromuscular block at the conclusion of surgery, normal ventilation was restored by 0.22 +/- 0.02 mg/kg intravenous nalbuphine (mean +/- SEM). Plasma levels of free norepinephrine, histamine, and cortisol did not increase after antagonism of the fentanyl-induced respiratory depression, but plasma concentration of epinephrine increased significantly but without significant hemodynamic changes. Minute ventilation was 1.5 +/- 0.4 L/min before and 11 +/- 1, 10 +/- 1, 11 +/- 1, and 10 +/- 1 L/min at 15, 30, 45, and 60 min after antagonism; corresponding PaCO2 levels were 56 +/- 2, 44 +/- 1, 49 +/- 7, 49 +/- 1, 42 +/- 1 mm Hg. The mean analogue pain score remained below 1.5. We conclude that nalbuphine effectively antagonizes fentanyl-induced respiratory depression without adverse endocrine and circulatory changes or loss of analgesia.

Topics: Adult; Catecholamines; Drug Evaluation; Endocrine Glands; Female; Fentanyl; Hemodynamics; Histamine; Humans; Hydrocortisone; Morphinans; Nalbuphine; Pain Measurement; Pain, Postoperative; Respiration; Time Factors

A retrospective study was carried out to review the intra-operative use of nalbuphine at the average dose of 1.5 mg/kg as a supplement to isoflurane and enflurane in balanced anaesthesia in 108 surgical patients. Intra-operative cardiovascular stability and the quality of emergence were examined. The amount of halogenated anaesthetic used was compared to the theoretical amount that would have been needed in the absence of nalbuphine. In 90% to 95% of patients, blood pressures remained within 20% of baseline for the duration of anaesthesia. At emergence, 80% of patients had no pain. Nalbuphine appeared to reduce halogenated anaesthetic requirements by approximately 50%. These promising results for the intraoperative use of nalbuphine need to be confirmed by controlled prospective studies.

Topics: Adult; Aged; Anesthesia, General; Blood Pressure; Enflurane; Female; Humans; Isoflurane; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Retrospective Studies

Six male patients were studied on the morning following upper abdominal surgery for highly selective vagotomy. Nalbuphine hydrochloride was infused i.v. at different rates that increased progressively in each hour over a 4-h period. In the last 15 min of each hour, the plasma nalbuphine concentrations were almost steady (73-68, 71-82, 116-113 and 201-208 ng ml-1). Patients and an observer made hourly assessments of pain and sedation. Although the changes in the pain and sedation scores were not significant, the patients' mean pain scores increased when the mean plasma nalbuphine concentrations were greater (greater than 82 ng ml-1), which suggested that nalbuphine analgesia had been reversed. Nalbuphine caused sedation and possibly induced amnesia which could invalidate retrospective assessment, since the patients' assessment of analgesic efficacy at the end of the study was good. No cardiovascular depression or significant decrease in the ventilatory rate was recorded.

Topics: Adult; Dose-Response Relationship, Drug; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain Measurement; Pain, Postoperative; Patient Acceptance of Health Care; Vagotomy, Proximal Gastric

Topics: Abdomen; Aged; Butorphanol; Female; Humans; Injections, Epidural; Lung; Male; Middle Aged; Morphinans; Morphine; Nalbuphine; Pain, Postoperative

Topics: Analgesics, Opioid; Buprenorphine; Humans; Morphinans; Pain, Postoperative

Twenty-five patients with moderate to severe pain after major upper abdominal surgery chose to receive nalbuphine on demand from a Cardiff Palliator for pain relief. An initial i.v. injection of nalbuphine 20 mg was followed by 5 mg given over 90s in response to each successful demand. A maximum of 20 doses (100 mg) hr-1 of nalbuphine was available, plus additional bolus doses. Twelve patients obtained good pain relief and completed the 5 hour observation period. 13 patients withdrew from the study, 8 because of inadequate pain relief and 2 because of side-effects. At least half the patients who complained of inadequate pain relief at the time had no subsequent memory of the events. Despite high dosage in some cases (up to 200 mg in an hour) no clinically important cardiovascular or respiratory effects were observed.

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Receptors, Opioid; Receptors, Opioid, kappa; Respiration

Topics: Analgesia; Butorphanol; Hemodynamics; Humans; Morphinans; Morphine; Pain, Postoperative; Respiration; Shock, Surgical

Nalbuphine (Nubain; Du Pont) 0.2 mg/kg (a new semisynthetic agonist-antagonist opioid) was compared with pethidine 0.75 mg/kg intravenously for analgesia after caesarean section in 70 patients. Statistical analysis of data showed that there was equivalence for analgesia, respiratory rate, cardiovascular parameters, side-effects and patient acceptance between the two drugs.

Topics: Adult; Cesarean Section; Female; Humans; Meperidine; Morphinans; Nalbuphine; Pain, Postoperative

The analgesic efficacy and tolerance of a single intramuscular injection of either buprenorphine (0.3 mg) or a buprenorphine (0.3 mg)/naloxone (0.2 mg) combination was compared in 70 patients suffering from moderate to severe pain after abdominal surgery. Patients in both treatment groups experienced good analgesia which was apparent within 10 minutes of administration and lasted for approximately 12 hours. The most frequently reported unwanted effects were drowsiness and/or sleepiness and nausea and/or vomiting which were of mild or moderate severity in most cases. No significant differences were seen between the two treatment groups with regard to the overall assessments of efficacy and tolerance.

Topics: Adult; Aged; Buprenorphine; Drug Combinations; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Morphinans; Naloxone; Pain, Postoperative

The effect of nalbuphine on common bile duct (CBD) pressure was studied by measurements through T-tubes on the first and second postoperative days after cholecystectomy and choledochotomy. Nalbuphine in a dose of 0.25 mg X kg-1 was injected intramuscularly in 11 patients, and changes in biliary pressure, heart and respiratory rate, blood pressure, and arterial blood gases were recorded during the subsequent four hours. The patients were free of pain, had stable common bile duct pressures and did not have any statistically significant changes in their vital signs. These results are similar to our previous observations during perioperative intravenous injection of nalbuphine. It is suggested that nalbuphine does not significantly change, or even may relax, the sphincter of Oddi, and can therefore be recommended as a safe analgesic in the postoperative period after extrahepatic biliary surgery.

Topics: Adult; Aged; Biliary Tract Diseases; Cholecystectomy; Cholelithiasis; Common Bile Duct; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Pressure

Topics: Analgesics; Bridged Bicyclo Compounds, Heterocyclic; Butorphanol; Cycloparaffins; Humans; Morphinans; Pain, Postoperative; Tetrahydronaphthalenes

Patient-controlled analgesia (PCA, intravenous self-application of narcotics) has been studied during the early postoperative period in 40 ASA I-III patients recovering from elective major and minor surgery (20 abdominal and 20 orthopaedic operations). Doses of 3.7 mg of the new agonist-antagonist opioid analgesic nalbuphine were available on demand, whenever the patients felt that pain relief was necessary, delivered by a microprocessor-controlled injection pump (On-Demand Analgesia Computer, ODAC) in response to use of a patient-controlled manual switch. The maximum dose/h was set at 28.2 mg, with a refractory time of 1 minute between successful demands. A continuous nalbuphine infusion (0.44 mg X h-1) was administered in addition in order to prevent obstruction of the catheter. The duration of the PCA period was 17.9 (0.4-28.0) h (median, range). During that time, 13.3 (1-45) demands per patient were recorded, resulting in median individual nalbuphine consumptions of 51.3 (8.1-1050.5) micrograms X kg-1 X h-1. Self-administration was characterized by considerable intra- and inter-individual variability. Following abdominal surgery significantly more nalbuphine was needed compared to orthopaedic patients, but it resulted in poorer pain relief. There were no statistically significant differences in drug requirements or pain scores between the sexes. Overall efficacy and patient acceptance proved to be good. When compared with previous conventional postoperative analgesia, the effectiveness of PCA was judged superior by about 57% of patients. Side effects (nausea, sweating) occurred in about 10% of patients but were usually of minor intensity. No serious circulatory or respiratory problems were observed during the period of PCA. Patient-controlled analgesia is a promising technique for the treatment of acute pain and for clinical pain research.

Topics: Adult; Female; Humans; Infusion Pumps; Male; Microcomputers; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Patient Participation; Self Administration

Topics: Aged; Butorphanol; Humans; Injections, Spinal; Male; Middle Aged; Morphinans; Pain, Postoperative; Prostatectomy

Topics: Aged; Anesthesia, General; Carbon Dioxide; Female; Fentanyl; Hemodynamics; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Postoperative Period; Respiration; Respiration, Artificial; Time Factors

Buprenorphin, 0,3 mg i.v., was used in 20 patients in the age of 51 to 75 years for analgesia after surgery for aortic aneurysm. Haemodynamic parameters of peripheral and pulmonary circulation, cardiac output, as well as blood gases were determined during routine postoperative controlled ventilation. The main results were an initial vasodilation and a decrease in heart rate, both of which reduce myocardial oxygen consumption. This effect is beneficial in the presence of sufficient volume substitution and optimal oxygenation in high-risk patients.

Topics: Aged; Aortic Aneurysm; Blood Pressure; Buprenorphine; Carbon Dioxide; Cardiac Output; Female; Hemodynamics; Humans; Male; Middle Aged; Morphinans; Oxygen; Pain, Postoperative

The effect of sublingual buprenorphine (Temgesic) as a premedicant and for postoperative pain relief compared with morphine/pethidine was studied in 50 patients scheduled for elective surgery of the knee joint. Twenty-five patients received buprenorphine 0.4 mg sublingually 1 h before surgery and the same dose on demand postoperatively. Twenty-five patients were given morphine intramuscularly (7.5 mg or 10 mg to females and males respectively) 1 h preoperatively. This group received pethidine (75 mg) intramuscularly on demand postoperatively. All the patients were anaesthetized with halothane N2O/O2 after induction with thiopentone. No significant differences were found with regard to sedation, dizziness, nausea and vomiting during the study period. Emergence shivering, confusion and restlessness just after termination of the operation were equal in the two groups. In the recovery room, however, there was a higher frequency of shivering (P less than 0.05) in the morphine group. During the first 24 h postoperatively the buprenorphine group was given an average of 3.8 doses compared with 2.3 in the pethidine group (P greater than 0.05). It is concluded, that buprenorphine sublingually is as good as morphine intramuscularly for premedication and therefore should be recommended to patients who wish to avoid injections. For postoperative pain relief the initial dose of buprenorphine should be given intravenously. Only minor and unimportant side effects were seen.

Topics: Administration, Oral; Adult; Buprenorphine; Female; Humans; Hypnotics and Sedatives; Male; Meperidine; Morphinans; Morphine; Orthopedics; Pain, Postoperative; Preanesthetic Medication

Buprenorphine 30 and 40 micrograms/kg was given as the sole intravenous analgesic in balanced anaesthesia to 12 patients undergoing cholecystectomy. Significant and severe respiratory depression was found 15 minutes after preoperative loading with buprenorphine. In the immediate postoperative period six patients were in pain. They were treated with naloxone 0.08-0.4 mg leading to a long lasting period of pain relief (median 22 hours).

Topics: Adult; Anesthesia, Intravenous; Buprenorphine; Depression, Chemical; Humans; Middle Aged; Morphinans; Naloxone; Pain, Postoperative; Prospective Studies; Respiration

Topics: Adult; Buprenorphine; Drug Interactions; Female; Humans; Morphinans; Naloxone; Pain, Postoperative

Topics: Adult; Aged; Clinical Trials as Topic; Ethics, Medical; Female; Humans; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative

Topics: Analgesics, Opioid; Humans; Morphinans; Nalbuphine; Pain, Postoperative; Self Administration

In 60 ASA class I or II patients given intravenous fentanyl for elective operations in doses large enough to produce postoperative respiratory depression, the intravenous administration of 20 mg nalbuphine resulted in prompt reversal of respiratory depression without loss of analgesia.

Topics: Adult; Blood Gas Analysis; Blood Pressure; Female; Fentanyl; Heart Rate; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Postoperative Period; Respiration; Tidal Volume

Since buprenorphine has been reported to be effectively analgesic yet free of addiction potential, two single-dose, double-blind, parallel studies were conducted to compare its analgesic activity and safety with those of morphine. The patients in each study consisted of patients experiencing moderate to severe postoperative pain. They were treated with an intramuscular injection of either 0.2 or 0.4 milligram of buprenorphine (Study I) or 0.15 or 0.30 milligram of buprenorphine (Study II) compared with 5.0 or 10.0 milligrams of morphine in both instances. Patients were interviewed prior to drug treatment and at 10, 20 and 30 minutes, and one, two, three, four, five and six hours postdose to determine pain intensity and relief. The degree of sedation, vital signs and side effects were evaluated. Buprenorphine generally appeared comparable to morphine in the onset and duration of action and in side effect liability.

Topics: Adolescent; Adult; Aged; Buprenorphine; Double-Blind Method; Drug Evaluation; Female; Humans; Injections, Intramuscular; Male; Middle Aged; Models, Biological; Morphinans; Morphine; Pain, Postoperative; Random Allocation; Time Factors

Topics: Anesthesia, Epidural; Buprenorphine; Humans; Morphinans; Pain, Postoperative

Topics: Adolescent; Adult; Aged; Buprenorphine; Female; Humans; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative

Topics: Adolescent; Adult; Aged; Buprenorphine; Humans; Infusions, Parenteral; Male; Middle Aged; Morphinans; Pain, Postoperative; Time Factors

Topics: Adult; Aged; Buprenorphine; Drug Evaluation; Female; Humans; Hysterectomy; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine; Time Factors

Topics: Adult; Buprenorphine; Epidural Space; Female; Humans; Injections; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative

In a prospective randomized trial, epidural buprenorphine was compared with intramuscular morphine for pain relief after spinal corrective surgery. Both forms of analgesia were given on demand and both produced excellent reduction of pain as assessed with visual linear analogue. The quality and duration of analgesia were similar for both groups of patients. Since the correct placement of epidural catheters could be done intraoperatively in difficult cases and since many patients for spinal corrective surgery have limited respiratory reserve, the authors feel that epidural buprenorphine provides an excellent alternative to conventional opiate analgesia after this type of surgery.

Topics: Adult; Buprenorphine; Epidural Space; Female; Humans; Injections; Injections, Intramuscular; Male; Middle Aged; Morphinans; Morphine; Pain, Postoperative; Prospective Studies; Random Allocation; Spinal Fusion

In a double-blind study with the use of subjective reports of patients as indices of analgesia, we compared the analgesic effect of oral nalbuphine and acetaminophen and determined the contribution of each to the efficacy of their combination. In this parallel 2 X 2 factorial study, 129 inpatients after surgery were randomly assigned to treatment with a single oral dose of nalbuphine hydrochloride (30 mg), acetaminophen (650 mg), the combination of nalbuphine (30 mg) and acetaminophen (650 mg), or placebo. In the factorial analysis, both the nalbuphine and acetaminophen effects were significant for virtually every measure of total and peak analgesia, whereas the interaction contrast was not significant for any measure of analgesic effect. This indicates that the analgesic effect of the combination represents the additive effect of its constituents and is consistent with the results of studies of combinations of codeine and other opioids with aspirin or acetaminophen. There were few adverse effects other than sedation, which occurred twice as frequently in patients treated with nalbuphine as in those receiving acetaminophen or placebo. Our data suggest that this combination should prove at least as effective as any currently marketed narcotic-containing combination. Since nalbuphine has less dependence liability than narcotics and exhibits a ceiling on respiratory depression, its combination with acetaminophen should also be safer than comparable narcotic combinations.

Topics: Acetaminophen; Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative; Random Allocation; Sleep Stages; Time Factors

Topics: Adult; Analgesics; Anesthesia, Epidural; Anesthesia, Local; Butorphanol; Female; Humans; Intraoperative Complications; Morphinans; Pain; Pain, Postoperative; Pregnancy; Sterilization, Tubal

Topics: Buprenorphine; Humans; Morphinans; Pain, Postoperative

In 10 healthy patients, buprenorphine was given as the postoperative analgesic (dosage: peripheral venous injection of 5 microgram/kg BW) after traumatological interventions in the lower extremities, which had been performed under barbiturate-induced halothane anaesthesia. The haemodynamic investigations revealed that buprenorphine has only a minor effect on the high pressure system. In the area of the pulmonary circulation, there was a significant increase in mean pulmonary artery pressure from 15.9 mm Hg to 17.8 mm Hg (+12%), as well as an increase in pulmonary vascular resistance by 16.5%. These changes were most marked 30 to 60 min after the administration of buprenorphine. When 2-3 1 O2/min were administered, none of the patients had PaO2 values of less than 100 mm Hg. 60 min after the injection, the PaCO2 value increased from 33.7 mm Hg to a maximum of 43.9 mm Hg. In 3 patients, PaCO2 increased to more than 45 mm Hg. All patients with greater increases of PaCO2 also evidenced greater increases in the pulmonary vascular resistance. Altogether the haemodynamic changes after buprenorphine administration following halothane anesthesia were not very distinct. In individual cases, however, there were greater increases in PaCO2. The cause of this could involve the additive effects of premedication and anaesthesia medication, and possibly the pain level as well. Both the increase in pulmonary artery pressure and the increase in total pulmonary vascular resistance in these patients were due to hypercapnia (von Euler-Liljestrand mechanism).

Topics: Adolescent; Adult; Anesthesia; Blood Gas Analysis; Buprenorphine; Female; Halothane; Hemodynamics; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Respiration

A six-point, incomplete block assay of sublingual buprenorphine and intramuscular morphine has been carried out, providing valid relative potency estimates of the two drugs in terms of total relief on both categorical and visual analog scales. Sublingual buprenorphine was about 15.5 times as potent as intramuscular morphine in terms of these total relief estimates. Similar relative potency estimates were obtained using first-dose-only data. There was no evidence of interaction by day in the crossover data, and the crossover study proved more efficient and provided tighter confidence limits. Sublingual buprenorphine produced a lower peak effect than intramuscular morphine. At equivalent peak effects, it produced longer-lasting analgesia. Side effect occurrence was roughly comparable for the two drugs, and no evidence of narcotic antagonist activity was seen after buprenorphine. The six-point assay proved to be effective in defining the dose-effect curves and relative potencies of the two drugs.

Topics: Administration, Oral; Buprenorphine; Dose-Response Relationship, Drug; Female; Humans; Injections, Intravenous; Male; Morphinans; Morphine; Pain, Postoperative

Efficacy and safety of oral nalbuphine in doses of 15 and 45 mg were compared with those of the standard oral analgesic codeine in single doses of 30 and 90 mg in 153 patients with acute postoperative pain; data on 20 more patients were excluded because they received potentially interfering medications. All patients had pain ranging from moderate to severe in intensity and most had severe pain related to orthopedic procedures or trauma. Estimates of relative potency showed that nalbuphine was three times as potent as codeine. The most common side effect was sedation, which was greatest in patients who received the higher doses of codeine and nalbuphine. The effects of oral nalbuphine are much like those of oral codeine in patients with acute postoperative pain.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Codeine; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Middle Aged; Morphinans; Nalbuphine; Pain, Postoperative

Topics: Adult; Aged; Anesthesia; Butorphanol; Enflurane; Female; Fentanyl; Humans; Meperidine; Middle Aged; Morphinans; Pain, Postoperative; Pelvis

Topics: Buprenorphine; Humans; Morphinans; Pain, Postoperative

Topics: Analgesics; Buprenorphine; Drug Evaluation; Humans; Morphinans; Morphine; Pain, Postoperative

Topics: Aged; Analgesics; Buprenorphine; Drug Evaluation; Female; Humans; Hypnotics and Sedatives; Infusions, Parenteral; Male; Middle Aged; Morphinans; Pain, Postoperative; Pentazocine; Postoperative Period

Topics: Adult; Analgesics; Blood Gas Analysis; Buprenorphine; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Postoperative Period

Buprenorphine was given intravenously to produce analgesia in the immediate postoperative period, the dose being titrated against the response of each patient in order to obtain complete freedom from pain. In 50 patients following lower segment Caesarean section under general anaesthesia, buprenorphine in the dose range 0.4-7.0 mg was found to be a potent, long lasting and safe analgesic. Serial blood gas estimations performed on ten of the patients confirmed the clinically observed lack of respiratory depression.

Topics: Adult; Buprenorphine; Cesarean Section; Dose-Response Relationship, Drug; Female; Humans; Morphinans; Pain, Postoperative; Pregnancy; Respiratory Insufficiency; Time Factors

1 Buprenorphine is a long-acting opiate analgesic. This study was designed to investigate the pharmacokinetics of this drug when given by the sublingual route to ten postoperative patients. Plasma levels of buprenorphine were measured by a specific radioimmunoassay. 2 Plasma levels of the drug following sublingual administration of 0.4 mg showed an apparent delay in absorption and then rose slowly to reach low but significant levels by 3 h. There was considerable variation in the time at which peak levels were achieved. The average systemic availability of the drug by this route was estimated to be 30% by 3 h. 3 Analgesic efficacy and duration of sublingual buprenorphine were assessed using demand analgesia. The analgesia was of about 9 h duration, similar to that achieved by parenteral administration of 0.3 mg of the drug to an equivalent group of patients. The sublingual dose caused a significant fall in the postoperatively elevated group of patients. The sublingual dose caused a significant fall in the postoperatively elevated plasma glucose, and prevented any further rise in plasma cortisol. 4 Reasons for the efficacy of the sublingual route are discussed and it is suggested that this route may be particularly appropriate for highly lipophilic drugs like buprenorphine.

Topics: Analgesia; Blood Glucose; Buprenorphine; Female; Humans; Hydrocortisone; Kinetics; Male; Middle Aged; Morphinans; Pain, Postoperative; Sex Factors; Tongue

Topics: Buprenorphine; Hemodynamics; Humans; Morphinans; Morphine; Pain, Postoperative

Topics: Butorphanol; Hemodynamics; Humans; Morphinans; Neoplasms; Pain, Postoperative; Respiration; Substance-Related Disorders

Temgesic Injection (buprenorphine), a potent analgesic agent, was given to 240 patients under 18 years of age during a year of monitored release. All but four had the product for the management of moderate or severe pain in the immediate post-operative period. Analgesia was reported as adequate or good in 90% of these young patients when it was assessed 2 and 4 hours after infection. There were no reports of side-effects commonly associated with strong analgesics and particularly antagonist-analgesics such as confusion, hallucination, blurred vision, dry mouth and lightheadedness. There were no serious respiratory or cardiovascular effects. The incidences of other events did not differ from those recorded in the much larger adult population of almost 8,000 patients. Buprenorphine is an effective analgesic suitable for use in the young post-operative patient.

Topics: Adolescent; Adult; Age Factors; Analgesia; Buprenorphine; Child; Child, Preschool; Drug Evaluation; Female; Humans; Injections, Intravenous; Male; Morphinans; Pain, Postoperative

Buprenorphine, a partial opiate-receptor agonist with potent analgesic properties, was given to 7548 patients in the immediate postoperative period. Ninety per cent of patients had good or adequate pain relief for at least 4 hours; there were few adverse effects and the incidence of drug-associated respiratory depression was estimated at less than 1%. There were no other side-effects of clinical note.

Topics: Adolescent; Adult; Aged; Buprenorphine; Child; Child, Preschool; Drug Evaluation; Female; Humans; Male; Middle Aged; Morphinans; Nausea; Pain, Postoperative; Respiratory Insufficiency; Time Factors; Vomiting

Topics: Buprenorphine; Humans; Injections; Morphinans; Pain; Pain, Postoperative

Topics: Buprenorphine; Humans; Infusions, Parenteral; Morphinans; Pain, Postoperative

Sublingual buprenorphine (0.4 mg) and intramuscular papaveretum (20 mg) were compared in sixty patients after abdominal hysterectomy. Though slower in onset of effect the sublingual tablets proved effective for pain relief and appeared to have a longer duration of action. The only side-effects of note were nausea and vomiting which occurred after both treatments. Haloperidol was tried as a long acting antiemetic and appeared successful.

Topics: Adult; Buprenorphine; Double-Blind Method; Evaluation Studies as Topic; Female; Humans; Kinetics; Morphinans; Pain, Postoperative; Papaverine; Random Allocation

The effect of buprenorphine on the cardiovascular system was examined in 11 patients during the period of reduced cardiac reserve after open-heart surgery. Within 10 minutes of giving the full analgesic dose (5 microgram/kg) intravenously the mean heart rate had fallen significantly by six beats/min. Although in two patients the mean arterial pressure fell by 24 mm Hg, there was no overall change in mean arterial pressure, cardiac output, or peripheral resistance. In a further six patients buprenorphine was used successfully as the sole analgesic after open-heart surgery. Buprenorphine appears to be safer than morphine for use in patients with reduced cardiac reserve and is of similar analgesic efficacy.

Topics: Adult; Aged; Blood Pressure; Buprenorphine; Cardiac Surgical Procedures; Heart Rate; Hemodynamics; Humans; Middle Aged; Morphinans; Pain, Postoperative

Topics: Butorphanol; Humans; Injections, Intramuscular; Injections, Intravenous; Morphinans; Pain; Pain, Postoperative

Buprenorphine, a new analgesic drug, was used for treatment of immediate postoperative pain in a group of 30 patients. A standard dose of 4 mug/kg was given IM. Onset of action occurred 10 to 20 min. later; pain relief was very good to good in 73%, fairly good in 23% and insufficient in 3%. Duration of action was very long (Mean + SEM: 360 +/- 32 min.) Side effects were few.

Topics: Aged; Analgesics; Chemical Phenomena; Chemistry; Female; Humans; Male; Middle Aged; Morphinans; Pain, Postoperative; Time Factors

Topics: Analgesics; Morphinans; Morphine; Morphine Derivatives; Pain; Pain, Postoperative