Double-blind evaluation of buprenorphine hydrochloride for post-operative pain.

In a double-blind, random assignment study of four groups of 40 patients, relief of severe pain with buprenorphine hydrochloride 0.2 mg or 0.4 mg was evaluated and compared with morphine sulphate 5 or 10 mg. Evaluations included pain intensity, pain relief, sedation and other effects for up to 12 hours after drug administration, following recovery of wakefulness from anaesthesia for major abdominal surgery. Analyses of five parameters showed that the four groups were statistically comparable and that buprenorphine hydrochloride is at least 50 times more potent than morphine sulphate and has a substantially longer duration of analgesic action. Further clinical evaluation is, therefore, recommended.     

Double-blind, Multiple-dose Comparison of Buprenorphine and Morphine in Postoperative Pain

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 anaesthesia 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 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 < 0.01). Significantly ( P < 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.     

Postoperative pain relief with naloxone, Severe respiratory depression and pain after high dose buprenorphine

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).     

Non-parenteral postoperative analgesia

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.     

Buprenorphine as premedication and as analgesic during and after light isoflurane-N2O-O2 anaesthesia. A comparison with oxycodone plus fentanyl

Sixty patients undergoing gynaecological laparotomies under isoflurane anaesthesia received 0.4 mg of buprenorphine sublingually or 0.12 mg/kg of oxycodone intramuscularly in random order for preanaesthetic medication. Patients premedicated with buprenorphine were given buprenorphine before, during and after anaesthesia and patients premedicated with oxycodone received fentanyl before and during anaesthesia and oxycodone after anaesthesia. Buprenorphine premedication produced less drowsiness and sedation and alleviated patients' apprehension significantly (P less than 0.05) less than oxycodone. Systolic and diastolic blood pressure and heart rate were significantly (P less than 0.05 to P less than 0.01) higher after intubation in the buprenorphine group when compared with the oxycodone plus fentanyl group. After anaesthesia, spontaneous respiration started rapidly; the return of consciousness and immediate recovery occurred at the same rate in both groups. In the recovery room moderate to severe pain was more common (P less than 0.05) in the oxycodone plus fentanyl group than in the buprenorphine group. The respiratory rate in the recovery room was lower among patients given buprenorphine, and two patients given buprenorphine developed severe respiratory depression. In the ward (2 to 24 h after operation) sublingual buprenorphine provided pain relief as good as intramuscularly administered oxycodone. No differences were noted in the incidence or severity of emetic symptoms between the groups. It is concluded that buprenorphine can provide good postoperative pain relief for gynaecological laparotomies performed under light isoflurane anaesthesia, but patients need to be monitored carefully after operation because of the possibility of respiratory depression.     

Pain relief after major abdominal surgery: a double-blind controlled comparison of sublingual buprenorphine, intramuscular buprenorphine, and intramuscular meperidine

In a double-blind randomized study of three groups of 18 patients scheduled for major abdominal surgery the efficacy and side effects of sublingual buprenorphine were tested and compared to intramuscular meperidine and buprenorphine. Single doses of either 75 mg of meperidine, 0.4 mg of sublingual buprenorphine, or 0.3 mg of intramuscular buprenorphine were used. Patients given buprenorphine as sublingual tablets were significantly more conscious in the immediate postoperative period (Glasgow Coma Scale) than when given buprenorphine or meperidine intramuscularly. Median pain intensity differences (PID) showed equal pain relief, whereas the summarized pain intensity differences (SPID) were significantly higher in the intramuscular buprenorphine group compared to the meperidine group. Three cases of respiratory acidosis in the meperidine group required IPPV treatment, and one case in the intramuscular buprenorphine group required treatment. Sedation and nausea were the most common side effects in all three groups. We conclude that sublingual buprenorphine is useful for relief of postoperative pain and exhibited administrative advantages, when the patients were able to cooperate.     

The respiratory depressive effects of intravenous buprenorphine in patients in an intensive care unit.

Buprenorphine hydrochloride, a new, potent, long-acting synthetic opiate analgesic, with partial agonist-antagonist activity, was administered intravenously to two groups of patients in an intensive care unit. Arterial blood was drawn for blood gas analysis before (control) and at regular intervals after drug administration, to determine the effects of intravenous buprenorphine on respiration in critically ill patients, each acting as his or her own control. Intravenous buprenorphine 0,4 mg (group I -- 10 patients) caused a significant reduction in mean respiration rate and an increase in mean PaCO2, but did not alter heart rate, PaO2 or base excess values. Intravenous buprenorphine 0,2 mg (group II -- 10 patients) was associated with a less significant reduction in the rate of breathing and elevation of PaCO2. Both 0,4 mg and 0,2 mg buprenorphine produced effective relief of pain, sedation, and reduction in restlessness, and allayed anxiety. Our results suggest that intravenous buprenorphine 0,2 mg can be safely recommended for the prolonged relief of postoperative pain in adults.     

A comparison of buprenorphine and pentazocine for the relief of postoperative pain

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.     

Epidural buprenorphine for postoperative analgesia. A controlled comparison with epidural morphine.

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.     

Evaluation of buprenorphine hydrochloride suppositories for postoperative pain relief]

An analgesic is often administered upon the occurrence of pain following surgery. Buprenorphine hydrochloride suppository (0.2 mg) was given immediately postoperatively to patients who had undergone surgery under general anesthesia. Post-operative pain has been observed after 782 +/- 41 minutes (n = 148, mean +/- SE) in the patients with suppository and 127 +/- 18 minutes (n = 57) in the control group (P less than 0.01). Analgesics were given to 68% of the control group within 2 hours, while it was given to 14% of the study group. Further 57% of the latter did not complain of any pain after 20 hours. The pharmacokinetics of buprenorphine was studied in 7 patients. Intrarectal administration of 0.2 mg buprenorphine suppository just after surgery had a sufficient analgesic action and did not induce any adverse reactions of any clinical importance.     

Analgesic effects of sublingual buprenorphine

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.     

Postoperative pain relief with high-dose epidural buprenorphine: a double-blind study

Forty-five patients scheduled for major abdominal or intrathoracic surgery were assigned at random to two different groups. One group received 0.3 mg and the other 0.9 mg of buprenorphine epidurally to abolish postoperative pain. The first dose was given immediately upon arrival in the ICU, irrespective of pain. Subsequent medication was given on demand. The duration of action and side-effects were recorded. Both doses produced excellent and long-lasting pain relief, but no statistically significant difference was found between the groups, with regard to either the duration of action or the occurrence of side-effects.     

Epidural buprenorphine--a double-blind study of postoperative analgesia and side effects

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.     

Sublingual Buprenorphine for Premedication and Postoperative Pain Relief in Orthopaedic Surgery

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.     

Relief of pain after surgery

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.     

COMPARISON BETWEEN BUPRENORPHINE AND PENTAZOCINE GIVEN I.V. ON DEMAND IN THE CONTROL OF POSTOPERATIVE PAIN

A double-blind comparison between buprenorphine and pentazocinewas performed in 20 patients using an on demand analgesic systemto provide analgesia after operation. The quality of analgesia,assessed subjectively, was good with both drugs and drug consumptionswere compatible with previous potency estimates. The mean dosesdemanded in 24 h of buprenorphine (1.68 mg) and of pentazocine(382 mg) are consistent with those found in other trials althoughthe between-patient variation was five- or six-fold. There wasno significant difference in side-effects between the two groups.Buprenorphine and pentazocine may be used successfully in anon demand system to provide relief of severe pain after operation.     

Effect of epidural buprenorphine on postoperative respiratory function]

The effects of epidural buprenorphine on postoperative respiratory function were studied using respiratory inductive plethysmography (RIP) in two groups of patients [(1) 0.1 mg (2) 0.2 mg] after upper abdominal surgery. Buprenorphine 0.1 mg group showed decreased respiratory rate and increased tidal volume. Decreases in the respiratory rate and the tidal volume were seen in buprenorphine 0.2 mg group and continued for 3-4 hrs after the epidural administration. However, there was no severe respiratory depression in either group. It seems that 0.1 mg of epidural buprenorphine may give a satisfactory postoperative pain relief and less respiratory depression, and RIP is a useful method for the measurement of postoperative respiratory function.     

Clinical evaluation of buprenorphine suppositories in postoperative patients--plasma concentrations and effects on the respiratory and circulatory system

The plasma concentrations of buprenorphine were measured and blood gas analysis was done after administration of buprenorphine suppositories (0.2 and 0.4 mg) or its intramuscular injection (0.2mg) in postoperative patients. The C max for 0.4mg suppositories was comparable to that for 0.2mg injection, whereas the T max for suppositories was as large as about 2 hrs in contrast to 1.5 hrs for 0.2mg injection. The size of AUC was in the following order: 0.4mg suppositories greater than 0.2mg injection greater than 0.2mg suppositories. Neither notable increase in PaCO2 nor decrease in respiration rate was observed after administration of the suppositories, indicating that the formulation will not cause clinically significant respiratory depression. No significant changes were observed in blood pressure or pulse rate. Buprenorphine suppositories are considered to be safe for use in postoperative patients. Percent pain relief in the suppository group was smaller than that in the injection group. This appears to be due to a slower rate of increase in the plasma levels of buprenorphine after administration of suppositories than that after intramuscular injection. Therefore, it seems practical to give this drug to postoperative patients before the start of pain.     

A long-term open, clinical and pharmacokinetic assessment of sublingual buprenorphine in patients suffering from chronic pain

Buprenorphine was administered as sublingual tablets to 70 patients suffering from chronic pain of malignant or non-malignant origin. Daily doses ranging from 0.4 mg to 3.2 mg were administered and good analgesia was reported by the majority of patients. The most common unwanted effects were drowsiness/sleepiness, nausea and/or vomiting and sweating which appeared to be dose related but the incidence of dizziness was not related to daily dose. The incidence of all these unwanted effects except drowsiness/sleepiness decreased after the first week's treatment. No buprenorphine related changes in vital signs or laboratory values were observed and no signs of tolerance or physical dependence were seen in the short term period after discontinuation of treatment. A significant positive correlation between buprenorphine plasma concentration and daily dose was observed but there was no correlation between plasma levels and pain relief.     

Longterm treatment with epidural opioids

During a 2-year period, 150 patients were treated with epidural opioids for more than 7 days; 89 received morphine and 61 buprenorphine. In 16 cases, medication was changed from morphine to buprenorphine, and in 6 from buprenorphine to morphine. In 19 patients in each group, the disease process was benign. The median daily dose of morphine was 17 mg given by an average of 2.9 injections; the corresponding figures in the buprenorphine group were 1.3 mg and 2.6 injections. The mean duration of treatment was 49 days (7-397) in the morphine group and 53 days (7-262) in the buprenorphine group. Satisfactory pain relief was achieved in 40 (45%) patients who received morphine and 41 (67%) patients given buprenorphine. Altering medication from morphine to buprenorphine improved analgesia in 32% of patients, while the reverse improved pain relief in a further 46% of the patients. Side effects were reported in 46% of patients given morphine and 20% given buprenorphine. Seventy-one patients were treated on an outpatient basis. In these cases, buprenorphine was administered for 89% of the total duration of treatment and morphine chloride for 52%.