O.15 mg Intrathecal buprenorphine applied for postoperative analgesia. A clinical double-blind study

In a double-blind, randomized study of 29 patients who underwent orthopedic procedures we studied the additional effect of intrathecal buprenorphine on isobaricpinal anesthesia and postoperative analgesia. The injections were 20 mg tetracaine (19 patients) or 20 mg tetracaine plus 0.15 mg buprenorphine (10 patients). In both groups the drugs were contained within a total volume of 4 ml cerebrospinal fluid. Progression and regression of the sensory blockade of spinal anesthesia were estimated with pinprick; the motor blockade was judged by the Bromage scheme. Postoperative pain was evaluated by the patients using an analogue scale after Scott and Huskisson. Arterial blood gases, respiratory rate, blood pressure, and heart rate were measured and other side-effects determined. Both groups were comparable in age, body weight, height and duration of operation (Table 1). The addition of buprenorphine elevated the sensory blockade by three segments both during spread and regression of anesthesia (Figs. 1, 2). Postoperative analgesia was better up to 8 h after injection (p less than 0.05), after 8 h pain levels were equal in test and control groups (Fig. 3). After buprenorphine patients became aware of pain sensation 13 h after injection; in the control group the pain-free interval lasted only 9 h (p greater than 0.05). There were no differences in the need for postoperative analgesics between both groups. The respiratory rate was lower during the whole period of observation (p less than 0.05). The mean values for PaCO2, pH and BE were similar in both groups (Fig. 4). PaO2 was elevated in the buprenorphine group. There was no essential alteration of blood pressure after buprenorphine. The pulse rate, however, was slightly diminished.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative analgesia in hip surgery A controlled comparison of epidural buprenorphine with intramuscular morphine

In a randomised controlled trial, epidural buprenorphine was compared with intramuscular morphine for postoperative analgesia in patients after hip surgery. Analgesia was given on demand and consisted of epidural boluses of 60 micrograms of buprenorphine in 10 ml of normal saline or intramuscular morphine 0.15 mg/kg. Both forms of analgesia produced excellent pain relief as assessed by the linear analogue scoring system. In both quality and duration of pain relief, no significant difference was found between the two forms of analgesia, but the total dose of epidural buprenorphine required was five times less than the equivalent dose of intramuscular morphine. No side effects attributable to epidural buprenorphine administration were found. The authors conclude that low dose epidural buprenorphine provides an excellent alternative to intramuscular opiates for pain relief after hip surgery.     

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.     

Periodic sublingual buprenorphine for pain relief after upper abdominal surgery

Analgesic effects were evaluated in patients who received sublingual administration of buprenorphine (0.2mg ampule for injection) as programmed every 8 hours for 3 days following upper abdominal surgery. Patients who received periodic sublingual buprenorphine obtained satisfactory postoperative analgesia and also required less analgesics than those who never received periodic administration of analgesics. Approximately one half of patients who received periodic sublingual buprenorphine required no additional analgesics. Arterial blood-gas analysis showed a significant increase in carbon dioxide tension after sublingual buprenorphine. One patient revealed marked respiratory acidosis after sublingual buprenorphine. These results suggest that periodic sublingual buprenorphine makes up for slow onset in sublingual administration and that it is also effective, convenient, and safe for pain relief after upper abdominal surgery. We, however, should pay attention to the respiratory depression caused by sublingual buprenorphine.     

Analgésie par la buprénorphine sublinguale dans la lithotritie extracorporelle rénale

The efficacy of sublingual buprenorphine given for premedication was assessed in 287 consecutive patients scheduled for extracorporeal shock wave lithotripsy (ESWL). The patients were randomly assigned to three groups. They were given 45 min before starting ESWL 5 mg midazolam orally in group 1 (n = 97), and 5 mg midazolam orally and 0.2 mg sublingual buprenorphine in group 2 (n = 97), and 5 mg midazolam orally and 0.4 mg sublingual buprenorphine in group 3 (n = 93). Analgesia was assessed with a simple three step verbal scale : no pain, moderate pain treated with simple analgesies (Spasfon®, Viscéralgine®), and exquisite pain requiring general anaesthesia. Sublingual buprenorphine provided good analgesia in 87 % of group 2 patients, and 88 % of group 3 patients (NS) whereas 70 % of group 1 patients experienced no pain (p < 0.05). The incidence of side-effects during the 12 h following ESWL, such as nausea, vomiting and drowsiness, was higher in group 3 (31 patients) than in group 2 (13 patients) (p > 0.01). No clinical respiratory depression occurred, although 11 patients in group 3 complained of drowsiness. It is concluded that premedication with 0.2 mg of sublingual buprenorphine provides efficient analgesia for ESWL and few side-effects.     

Epidural buprenorphine for postoperative analgesia after hip operations

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.     

Comparison of intravenous buprenorphine or fentanyl and epidural buprenorphine for pain relief after upper abdominal surgery

In three groups [(1) intravenous buprenorphine (0.1mg) or (2) fentanyl (100 micrograms.hr-1) and (3) epidural injection of buprenorphine (0.1mg diluted with 10ml normal saline)], we determined the effects of postoperative pain relief in patients after upper abdominal surgery. There are no differences in postoperative analgesia in the three groups, but respiratory depression was seen in some patients who had intravenous buprenorphine or fentanyl. We conclude that epidural injection of buprenorphine is a useful method for postoperative analgesia because of little adverse effect. As respiratory depression caused by buprenorphine was reversed with naloxone, it is not necessary to employ fentanyl instead of buprenorphine.     

COMPARISON OF MORPHINE AND SUBLINGUAL BUPRENORPHINE FOLLOEING ABDOMINAL SURGERY

In a prospective Study, patients undergoing abdominal surgerywere allocated randomly to receive intermittent morphine lOmgi.m.(n —41) or a lingle injection of buprenorphine 0.3 mgi.m.followed by sublingual buprenorphine 0.4 mg every 6h (n=39)for 3 days following operation. Patients receiving buprenorphinewere allowed additional morphine, if required. Pain (cores (linearanalogue scale) in those patients receiving regular sublinguftlbuprenorphine were consistently less than in those receivingintermittent morphine i.m. Half the patients receiving buprenorphinerequired no additional analgesia; only 15% required additionalarmigi-nin after the first day following operation. Arterialblood-gas analyses showed m'gnrfirant hypozaemU and significantlygreater carbon dioxide tensions in those receiving buprenorphine.These results suggest that a regimen based on the use of sublingualbuprenorphine provides pain relief comparable to that providedby intermittent opiates     

Lumbar epidural buprenorphine for postoperative pain relief following hepatectomy

The induction of postoperative pain relief with lumbar epidural or intramuscular buprenorphine was studied in 30 patients undergoing hepatectomy. When patients first complained of pain after surgery, 0.06 mg or 0.12 mg of buprenorphine in 10 ml or 20 ml of saline was administered through an epidural catheter inserted at the L3-4 interspace, or 0.12 mg was administered intramuscularly. Two of seven patients receiving epidural buprenorphine 0.12 mg in 10 ml saline were completely pain-free, and the other five patients in this group had only slight pain. Four of eight patients receiving epidural buprenorphine 0.12 mg in 20 ml saline were completely pain-free, and the other four patients in this group had only slight pain. Epidural buprenorphine 0.06 mg in 20 ml saline and intramuscular buprenorphine 0.12 mg each yielded only incomplete analgesia. The duration of analgesia of epidural buprenorphine 0.12 mg administered at the lumbar level was about 8 h. There were no significant changes over time in circulatory or respiratory variables induced by buprenorphine. No patient had serious adverse effects. Lumbar epidural administration of buprenorphine 0.12 mg diluted to 10 or 20 ml (20 ml might be preferable) with saline is recommended for induction of postoperative analgesia following hepatectomy.     

Analgesic effects of epidurally administered fentanyl for postoperative pain relief--comparison with buprenorphine]

We did a retrospective study on 177 patients after upper and lower abdominal surgery, and compared the efficacy of epidural administration of fentanyl and that of buprenorphine for postoperative pain relief. In fentanyl (F) group, 73 patients received fentanyl 0.1 mg with saline 8 ml epidurally after operation, followed by a constant rate infusion of 0.025 mg.hr-1 for 18-24 hrs. In buprenorphine (B) group, 104 patients, received buprenorphine 0.2 mg with saline 9 ml epidurally. After upper abdominal surgery, 33 patients (76.7%) in F group and 27 patients (52.9%) in B group obtained satisfactory analgesia (P < 0.05). The difference of the degree of analgesia after lower abdominal surgery was not significantly different in both groups. Respiratory depression occurred in 19 patients in B group and 5 patients in F group (P < 0.05). It is concluded that epidural fentanyl delivered by continuous infusion offers a significant advantage compared with epidural buprenorphine for postoperative pain relief following upper abdominal surgery.     

Postoperative analgesia in children who have genito-urinary surgery A comparison between caudal buprenorphine and bupivacaine

A study conducted on 40 children, aged 1-11 years, who had genito-urinary surgery compared the quality and duration of analgesia after caudal blocks in two groups of patients. Group 1 (n = 20) received caudal bupivacaine 0.25% and group 2 (n = 20) caudal buprenorphine 4 micrograms/kg; each received 0.5 ml/kg body weight. Patients were operated on under general anaesthesia. Postoperative behaviour and severity of pain were measured on a 3-point scale. The results indicate that caudal buprenorphine provides excellent postoperative analgesia in children comparable to caudal bupivacaine in the early postoperative period. Buprenorphine proved better in the late postoperative period. Analgesia lasted from 20 hours to more than 24 hours after caudal buprenorphine with fewer side effects.     

Analgesia for Circumcision in Children: A Comparison of Caudal Bupivacaine and Intramuscular Buprenorphine

In 44 boys undergoing day case circumcision, analgesia was provided with either buprenorphine 3 μg/kg intramuscularly or 0.25% bupivacaine 0.5 ml/kg by caudal injection. Both methods provided good analgesia; the frequency of side effects was less with caudal analgesia; and restoration to normal activity 24 h after operation was greater than with buprenorphine.     

COMPARISON OF EXTRADURAL BUPRENORPHINE AND EXTRADURAL MORPHINE AFTER CAESAREAN SECTION

Fifty-seven women received extradural morphine 3 mg, buprenorphine0.18 mg or buprenorphine 0.09 mg after elective Caesarean sectioncarried out under extradural bupivacaine. Supplementary sublingualbuprenorphine was available on demand. Ten-centimetre visualanalogue pain scores were completed regularly; emesis, pruritisand urinary retention were recorded for 24 h. Patients who receivedbuprenorphine 0.09 mg had more pain, and required more supplementaryanalgesia, than those who received morphine 3 mg. Pain scoresand analgesic requirements after buprenorphine 0.18 mg werenot significantly different from either of the other two groups.Emesis was not significantly different in the three groups.More itching occurred after morphine 3 mg and buprenorphine0.18 mg than after buprenorphine 0.09 mg; pruritis of the face,legs and perineum was more common after morphine than buprenorphine.Twenty-eight percent of patients without a urinary catheterdeveloped retention of urine. Seventy-five to 84% of patientswere satisfied with analgesia during the first day after operation.Analgesia and adverse effects were similar when morphine 3 mgor buprenorphine 0.18 mg was given extradurally after Caesareansection.     

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.     

Uso da buprenorfina transdérmica na dor aguda pós‐operatória: revisão sistemática

Background and objectivesPostoperative pain is still a major concern in several surgical procedures. Multimodal analgesia is best for postoperative pain management; however, opioid therapy is still the main treatment for pain after surgical procedures. Transdermal buprenorphine is a partial μ agonist opioid widely used for chronic pain syndromes, with limited evidence for acute postoperative pain. A systematic review of studies examining transdermal buprenorphine for acute pain management after surgery was conducted.ContentsData from PubMed, Embase, The Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL via EBSCOhost, and LILACS were reviewed, including randomized clinical trials that evaluated total postoperative pain, postoperative analgesic consumption, drug‐related side effects and patient satisfaction with analgesia regimen. Data from nine studies (615 patients) were included in this review. Most studies initiated transdermal buprenorphine use 6 to 48 hours before surgery, maintaining use from 1 to 8 days after the procedure. Most studies showed lower or similar postoperative pain scores, postoperative analgesic consumption and patient satisfaction comparing buprenorphine to placebo, tramadol, celecoxib, flurbiprofen and parecoxib. The incidence of side effects varied between studies, with most showing no increase in drug‐related side effects with buprenorphine use, except one study, which compared buprenorphine to oral tramadol, and one to transdermal fentanyl. However, most results were derived from evidence with an overall high or unclear risk of bias.ConclusionsAlthough more studies are necessary, initial results show that transdermal buprenorphine seems to be an effective and safe opioid choice for management of acute postoperative pain.     

A double-blind comparison of the relative efficacy, side effects and cost of buprenorphine and morphine in patients after cardiac surgery

The analgesic efficacy, side effects and cost of administration of regimens of intravenous buprenorphine and intravenous morphine were compared in a randomized double-blind trial performed during the first 24 h after cardiac surgery. Seven patients received buprenorphine by intermittent intravenous injection and six received morphine by continuous infusion. Both these regimens provided good analgesia for the entire 24 h period, with only mild pain at rest and moderate pain on vigorous coughing. Both regimens also produced mild respiratory depression but this was not of clinical importance: the mean arterial PCO2 in both groups was less than 45 mmHg after extubation. The major difference between drugs in the clinical setting was the ease of administration. Buprenorphine had no narcotic code restriction and could be given by intermittent intravenous injection, whereas morphine required checking and handling as a restricted drug and administration by continuous intravenous infusion. When labour and material costs were computed, over the first 24 postoperative hours, it cost $19.76 per patient to administer morphine, but only $3.16 to administer buprenorphine. Thus the use of buprenorphine injections for the first 24 h after cardiac surgery produced pain relief and respiratory depression comparable to that produced by a morphine infusion, but with a significant cost saving in terms of labour and materials.     

Epidural buprenorphine for pain relief after major abdominal surgery. A controlled comparison with epidural morphine

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.     

Prolonged and biphasic respiratory depression following epidural buprenorphine

Ventilatory sensitivity to carbon dioxide was measured in six healthy volunteers before, and at various times up to 20 hours after, administration of epidural buprenorphine 0.15 mg with a modified Read rebreathing technique. The carbon dioxide response curves were depressed in a time-dependent, prolonged and biphasic manner. Significant depression was seen in the intercept values at an end tidal carbon dioxide of 7.2 kPa, for mouth occlusion pressure (p less than 0.01), tidal volume (p less than 0.05) and minute ventilation (p less than 0.05). A significant reduction of slope was obtained only for minute ventilation. Linear regression of respiratory rate changes during carbon dioxide stimulation, did not reach statistical significance. In conclusion, these data indicate that epidural buprenorphine, despite a high lipid solubility, causes respiratory depression to the same extent as epidural morphine. Surveillance of patients who receive epidural buprenorphine for postoperative pain relief is necessary.     

Postoperative pain relief by topical lidocaine in the surgical wound of hysterectomized patients

Background: To improve postoperative analgesia, local anesthetics have been administered perioperatively as infiltration or as aerosol in the surgical area. A previous study showed good analgesic effects by topical lidocaine in the wound in minor extraabdominal surgery (herniorraphy), while the same treatment in minor lower laparotomies did not improve postoperative analgesia. The present study investigated the effect of topical wound anesthesia using lidocaine aerosol on postoperative pain following major lower abdominal surgery.
Methods: Postoperative pain and analgesic requirements were studied in a double-blind randomized trial including 30 hysterectomized patients. Patients were randomized to receive single wound treatment either with lidocaine aerosol 500 mg (100 mg/ml; Xylocain® aerosol, ASTRA, Sweden) (n=15) or placebo aerosol (n=15). Postoperative pain was evaluated by visual analogue scale (VAS). Requirements of opiate analgesics (buprenorphine) after surgery were monitored.
Results: Lidocaine aerosol induced a significantly ( P <0.001) better analgesia at rest (VAS) and a significant ( P <0.001) reduction in postoperative requirements of buprenorphine during the first 24 hours after surgery compared to placebo aerosol. Differences between the groups in pain scores (VAS) and buprenorphine requirements during the second postoperative day were not significant. Mean pain scores upon mobilization 24 h after surgery were significantly lower in the group receiving lidocaine aerosol ( P <0.05). The plasma lidocaine concentration 4 h after the administration of lidocaine was well below toxic level and plasma lidocaine was detectable 48 h postoperatively. No drug-related side effects were reported.
Conclsuion: A single dose of lidocaine aerosol topically administered in the surgical wound of hysterectomy patients improved analgesia during the first postoperative day with minimal risk of side effects.     

Pain Relief with Epidural Buprenorphine After Spinal Fusion: A Comparison with Intramuscular Morphine

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.