Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.     

Epidural fentanyl markedly improves thoracic epidural analgesia in a low-dose infusion of bupivacaine, adrenaline and fentanyl. A randomized, double-blind crossover study with and without fentanyl

BACKGROUND: The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief, and side effects when removing fentanyl from an optimally titrated epidural infusion consisting of bupivacaine, fentanyl and adrenaline. METHODS: A prospective, randomized, double-blind, crossover study was carried out in 20 patients after major upper abdominal surgery requiring a large longitudinal incision. Patients with only mild pain when coughing during thoracic epidural infusion of about 10 ml per hour of bupivacaine 1 mg x ml(-1), fentanyl 2 microg x ml(-1), and adrenaline 2 microg x ml(-1) were included. On the 1st and 2nd postoperative days, each patient was given a double-blind epidural infusion, at the same rate, with or without fentanyl. The effects were observed for 6 h or until pain when coughing became unacceptable in spite of rescue analgesia. Rescue analgesia consisted of up to two patient-controlled epidural bolus injections (4 ml) per hour and intravenous morphine if necessary. RESULTS: Main outcome measures, i.e. pain intensity when coughing and at rest, increased (P<0.001) when fentanyl (19.2+/-5.2 microg x h(-1)) was omitted from the epidural infusion: after 6 h pain intensity when coughing had increased to unacceptable levels in spite of increased consumption of rescue bupivacaine and adrenaline (P<0.001). Within 15-20 min after restarting the triple epidural mixture with fentanyl, pain intensity was again reduced to mild pain when coughing. CONCLUSIONS: A low dose of epidural fentanyl (20 microg x h(-1)) markedly improved the pain-relieving effect of bupivacaine and adrenaline infused epidurally at a thoracic level after major upper abdominal surgery. This dose of fentanyl is much too small to relieve severe dynamic pain when given systemically. Therefore, this study indirectly supports the view that a low-dose thoracic epidural infusion of fentanyl has a spinal analgesic site of action.     

Epinephrine markedly improves thoracic epidural analgesia produced by a small-dose infusion of ropivacaine,fentanyl, and epinephrine after major thoracic or abdominal surgery: a randomized,double-blinded crossover study with and without epinephrine

We have shown that epinephrine markedly improves the analgesic effect of a thoracic epidural infusion of bupivacaine and fentanyl. Ropivacaine has an intrinsic vasoconstrictive effect, and epinephrine may therefore not have the same pharmacokinetic interaction in a ropivacaine-fentanyl infusion; but a possible spinal cord alpha(2)-agonist effect of epinephrine would give the same positive pharmacodynamic interaction with ropivacaine and fentanyl during epidural analgesia. In a prospective, randomized, crossover study, a thoracic epidural infusion of ropivacaine 1 mg/mL and fentanyl 2 microg/mL with or without epinephrine 2 microg/mL was given to 12 patients in a double-blinded manner after major thoracic or upper abdominal surgery. Main outcome measures were pain intensity at rest and when coughing, evaluated on a visual analog scale. Extent of sensory blockade was evaluated by determining dermatomal hypoesthesia to cold. Pain increased (P < 0.001) and hypoesthetic dermatomal segments decreased (P < 0.001) when epinephrine was omitted from the triple epidural infusion. After 3 h without epinephrine, pain intensity when coughing was unacceptable despite rescue analgesia. After restarting the triple epidural mixture with epinephrine, pain was again reduced to mild pain when coughing, and the sensory blockade was restored. The mixture with epinephrine caused less nausea and facilitated mobilization. We conclude that epinephrine improves the pain relief and reduces the side effects of a thoracic epidural infusion of ropivacaine and fentanyl after major thoracic or upper abdominal surgery. IMPLICATIONS: Epidural epinephrine markedly improves the pain relief and sensory blockade of a small-dose thoracic epidural infusion of ropivacaine and fentanyl. Nausea was reduced, and mobilization of the patients was facilitated.     

Epinephrine added to a lumbar epidural infusion of a small-dose ropivacaine-fentanyl mixture after arterial bypass surgery of the lower extremities

BACKGROUND: The addition of epinephrine (2 micro g.ml-1) to a thoracic epidural infusion of an opioid-local anesthetic mixture improves analgesia. Here, we studied whether epinephrine could improve analgesia also at lumbar level, when added to an epidural infusion of a low-dose ropivacaine-fentanyl mixture after arterial bypass surgery of the legs. METHODS: Patients in group RFE (n = 21) received a postoperative epidural infusion containing ropivacaine (1 mg.ml-1), fentanyl (2 micro g.ml-1), and epinephrine (2 micro g.ml-1). Patients in group RF (n = 25) received a similar infusion without epinephrine. The infusion speed was 1 ml.10 kg-1. h-1. The infusion was scheduled for 48 h. RESULTS: Epinephrine did not reduce the need for rescue pain medication. Visual analog scale scores (VAS) for pain at rest were low and similar in the groups. Pain intensity was stronger during leg movement [mean VAS 1.5-2.6 (range 0-9)], but it was not affected by the coadministration of epinephrine. The groups did not differ concerning frequency and severity of side-effects. Epinephrine did not reduce fentanyl plasma concentrations. Ropivacaine concentrations were slightly lower in group RFE only in the samples 6 h from the start of the infusion, but not anymore on the first and second postoperative day. CONCLUSION: In the dosage used here, epinephrine did not improve epidural lumbar analgesia. Different distances from the epidural application site to the alpha2-adrenergic receptors of the spinal cord, and differing epinephrine dose requirements may explain why epinephrine as an additive improves epidural analgesia at thoracic, but not at lumbar level.     

A randomized,double-blinded comparison of thoracic epidural ropivacaine,ropivacaine/fentanyl,or bupivacaine/fentanyl for postthoracotomy analgesia

Epidural ropivacaine has not been compared with bupivacaine for postthoracotomy analgesia. Eighty patients undergoing elective lung surgery were randomized in a double-blinded manner to receive one of three solutions for high thoracic epidural analgesia. A continuous epidural infusion of 0.1 mL. kg(-1). h(-1) of either 0.2% ropivacaine, 0.15% ropivacaine/fentanyl 5 micro g/mL, or 0.1% bupivacaine/fentanyl 5 micro g/mL was started at admission to the intensive care unit. We assessed pain scores (rest and spirometry), IV morphine consumption, spirometry, hand grip strength, PaCO(2), heart rate, blood pressure, respiratory rate, and side effects (sedation, nausea, vomiting, and pruritus) for 48 h. Thoracic epidural ropivacaine/fentanyl provided adequate pain relief similar to bupivacaine/fentanyl during the first 2 postoperative days after posterolateral thoracotomy. The use of plain 0.2% ropivacaine was associated with worse pain control during spirometry, larger consumption of IV morphine, and increased incidence of postoperative nausea and vomiting. Morphine requirements were larger in the ropivacaine group, with no differences between bupivacaine/fentanyl and ropivacaine/fentanyl groups. Patients in the ropivacaine group experienced more pain and performed worse in spirometry than patients who received epidural fentanyl. There was no significant difference in motor block. We conclude that epidural ropivacaine/fentanyl offers no clinical advantage compared with bupivacaine/fentanyl for postthoracotomy analgesia. IMPLICATIONS: Thoracic epidural ropivacaine/fentanyl provided adequate pain relief and similar analgesia to bupivacaine/fentanyl during the first 2 postoperative days after posterolateral thoracotomy. Plain 0.2% ropivacaine was associated with worse pain control and an increased incidence of postoperative nausea and vomiting. We conclude that epidural ropivacaine/fentanyl offers no clinical advantage compared with bupivacaine/fentanyl for postthoracotomy analgesia.     

Stability of an epidural analgesic solution containing adrenaline, bupivacaine and fentanyl

BACKGROUND: A low dose solution of adrenaline 2 microg x ml(-1), fentanyl 2 microg x ml(-1) and bupivacaine 1 mg x ml(-1) has been reported to give superior pain control when used for epidural analgesia after major surgery. The present paper describes the compounding and chemical stability of this triple-component solution during storage and use. METHODS: Sterile triple-component concentrates (11X) were diluted by the use of gas isolator technology to give ready-to-use infusion solutions. Eight solutions were analysed by reverse phase high-performance liquid chromatography (HPLC) methods, and assays were performed on 1, 45, 90 and 180 days after storage at 2-8 degrees C. After 180 days the solutions were subsequently stored at 22 degrees C for four days before they were reanalysed. HPLC quantification of adrenaline was also performed on samples from solutions given to 28 different patients. RESULTS: The concentration of adrenaline and fentanyl decreased approximately 3.5% from 1 to 180 days at 4 degrees C and four days at 22 degrees C. The corresponding figure for bupivacaine was an apparent increase by 2.4% in concentration. No absorption to the polypropylene plastic bags of fentanyl and bupivacaine was detected. None of the 28 samples derived from used infusion bags contained less than 95% of the declared content of adrenaline. CONCLUSIONS: The triple-component epidural analgesic solution remained stable during six months of cold storage, followed by four days of storage at room temperature. No significant degradation of adrenaline was observed in infusion solutions returned from the wards.     

Bupivacaine 0.1% does not improve postoperative epidural fentanyl analgesia after abdominal or thoracic surgery

Epidural infusions of fentanyl, in a 10 micrograms.ml-1 concentration, combined with bupivacaine 0.1% were compared with epidural infusions of fentanyl alone for postoperative analgesia following abdominal or thoracic surgery. There were no detectable differences between the two groups in analgesia (mean visual analogue scale pain scores ranging between 15-35 mm), average infusion rates of 7-9 ml.hr-1, and serum fentanyl concentrations which reached 1-2 ng.ml-1. There was no difference in postoperative pulmonary function (pH, PaCO2, SaO2), or bowel function (time to flatus or po fluids). The incidence of side-effects including somnolence, nausea and vomiting, pruritus and postural hypotension was also similar. Of the patients receiving fentanyl and bupivacaine 0.1%, three developed a transient unilateral sensory loss to pinprick and ice, and two of these patients had unilateral leg weakness equal to a Bromage 1 score. The addition of bupivacaine 0.1% does not improve epidural infusions of fentanyl using a 10 micrograms.ml-1 concentration following abdominal or thoracic surgery.     

Does adrenaline improve epidural bupivacaine and fentanyl analgesia after abdominal surgery?

The alpha-adrenergic agonists have been demonstrated to have synergistic effects with opioids and local anesthetics in animal research. The present study was performed to determine whether the addition of adrenaline improves the analgesic effects of an epidural infusion of a combination of fentanyl and bupivacaine after abdominal surgery. We studied 90 ASA 1 or 2 patients scheduled for abdominal surgery under epidural anaesthesia, with or without general anaesthesia. Patients were randomly divided into two groups to receive a postoperative epidural infusion of fentanyl 5 micrograms/ml in bupivacaine 0.2%, with or without adrenaline 5 micrograms/ml, at a rate of 2 ml/h for more than 48 hours. Postoperative pain relief was assessed using visual analog scales (VAS), both at rest and during coughing, at 2, 24, and 48 hours after surgery. The number of rescue analgesics and side-effects such as nausea, vomiting, pruritus, respiratory depression, headache, muscle weakness, and hypotension were recorded. Patients who received adrenaline (n = 40) reported significantly lower mean VAS scores than those who received no adrenaline (n = 37), both at rest at 24 hours postoperatively and during coughing at 24 and 48 hours. The number of additional analgesics and incidence of side-effects did not differ between groups. In conclusion, the results of the present study demonstrate that the addition of adrenaline to a combination of fentanyl and bupivacaine improves the quality of epidural analgesia after abdominal surgery. Under the conditions of the study, we did not detect any disadvantage from the addition of adrenaline.     

Postoperative analgesia after radical retropubic prostatectomy: a double-blind comparison between low thoracic epidural and patient-controlled intravenous analgesia

BACKGROUND: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study. METHODS: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 microg/ml fentanyl, and 2 microg/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl. RESULTS: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group x time interaction was found in the Short Form-36. CONCLUSIONS: The authors found evidence for better pain relief and improved expiratory muscle function in patients receiving low thoracic epidural analgesia compared with patient-controlled analgesia for radical retropubic prostatectomy. Low thoracic epidural analgesia can be recommended as a good method for postoperative analgesia after abdominal surgery.     

Obstetric epidural analgesia with mixtures of bupivacaine, adrenaline and fentanyl

We performed a double-blind comparison of six solutions for epidural analgesia in 90 healthy Chinese women with uncomplicated pregnancies. Patients were randomly allocated to receive 10 ml bupivacaine 0.125% or 0.25% plain, bupivacaine 0.125% with adrenaline 1.25 micrograms/ml, bupivacaine 0.25% with adrenaline 2.5 micrograms/ml or the latter two solutions with added fentanyl 50 micrograms. Analgesia was unsatisfactory in 30% of the bupivacaine 0.125% groups without fentanyl. The addition of adrenaline, compared with bupivacaine 0.25% plain, gave faster onset and longer duration of analgesia (p less than 0.05) which was similar to that found in both fentanyl groups. There were no differences in method of delivery or neonatal Apgar scores among groups. The least concentrated mixture that gave the best analgesia was the combination of bupivacaine 0.125% with adrenaline 1.25 micrograms/ml and fentanyl 50 micrograms.     

Postoperative epidural analgesia after upper abdominal surgery: the effects of low concentrations of bupivacaine combined with a low dose of opioid]

The efficacy and safety of postoperative analgesia with continuous epidural infusion of either morphine or fentanyl in combination with a low dose of bupivacaine were evaluated in 205 patients after upper abdominal surgery. Each patient was given bupivacaine alone (0.125% or 0.25%) or one of six combinations; 0.25%, 0.125%, or 0.0625% bupivacaine with morphine (M: 10 micrograms.ml-1) or fentanyl (F: 1 microgram.ml-1). After injection of 6 ml of each solution at the end of surgery, continuous epidural infusion was started at a rate of 4.2 ml.hr-1 for 48 hr. The degree of pain relief was assessed by the necessity of supplementary analgesics, the visual analogue pain scale and the Prince Henry pain scale. The most effective analgesic situation was obtained with the 0.25% M and the 0.25% F groups. The 0.125% M and 0.125% F groups showed adequate analgesia for elderly patients with few side effects. Regarding the plasma catecholamines measured 24 hr after the surgery, there was no significant change in fentanyl groups as well as in the group given 0.125% bupivacaine alone. Although the incidence of hypotension and pruritus was slightly higher in morphine groups, no patient developed respiratory depression. It is suggested, therefore, that a small dose of opioid should be added when continuous epidural infusion is required.     

Postoperative epidural analgesia in children after major orthopaedic surgery. A randomised study of the effect on PONV of two anaesthetic techniques: low and high dose i.v. fentanyl and epidural infusions with and without fentanyl

BACKGROUND: The study was performed in order to improve postoperative pain management in children after major orthopaedic surgery. Two different anaesthetic techniques (sevoflurane-low fentanyl and propofol-higher fentanyl) and two different epidural mixtures (bupivacaine 1.5 mg ml(-1) and adrenaline 2 microg ml(-1) compared with bupivacaine 1 mg ml(-1), adrenaline 2 microg ml(-1) and fentanyl 2 microg ml(-1)) were investigated with regard to postoperative analgesia and side effects, primarily postoperative nausea and vomiting (PONV). METHODS: Forty-two children were randomised into one of three groups: sevoflurane anaesthesia and epidural solution with fentanyl (SBAF); sevoflurane anaesthesia and epidural solution without fentanyl (SBA); propofol anaesthesia and epidural solution without fentanyl (PBA). RESULTS: Including fentanyl in the epidural mixture resulted in excellent postoperative analgesia without any need of i.v. opioids. However, 7 out of 16 children were nauseated and needed antiemetic drugs. On average, a 55-75% higher dose of bupivacaine was necessary to assure adequate analgesia when an epidural mixture without fentanyl was used. In addition, significantly more children needed i.v. opioids. Under these conditions there was no significant difference in pain scoring between the groups. There was significantly less nausea and less use of antiemetic drugs in children having epidurals without fentanyl in the sevoflurane groups. The same tendency, although not significant, was observed in the whole material. Sevoflurane anaesthesia resulted in less PONV than propofol anaesthesia, probably due to the higher amount of intravenous fentanyl used with the latter. This difference was not significant due to the small number of children included. Incidence of pruritus related significantly to epidural fentanyl. CONCLUSION: A satisfactory postoperative analgesia can be achieved with both epidural mixtures used in the study. Epidural fentanyl results in better analgesia, but significantly more PONV and greater use of antiemetic drugs. Omitting epidural fentanyl results in less PONV, but significantly less profound analgesia and a need for additional treatment with i.v. opioids, in addition to a 55-75% higher epidural bupivacaine infusion. Both epidural treatments result in high and similar patient satisfaction and no serious complications. The study could not show any significant difference between the effect of sevoflurane and propofol anaesthesia on PONV.     

Postoperative Analgesia after Radical Retropubic Prostatectomy: A Double-blind Comparison between Low Thoracic Epidural and Patient-controlled Intravenous Analgesia

Background: Postoperative pain after radical retropubic prostatectomy can be severe unless adequately treated. Low thoracic epidural analgesia and patient-controlled intravenous analgesia were compared in this double-blind, randomized study.

Methods: Sixty patients were randomly assigned to receive either low thoracic epidural analgesia (group E) or patient-controlled intravenous analgesia (group P) for postoperative pain relief. All patients had general anesthesia combined with thoracic epidural analgesia during the operation. Postoperatively, patients in group E received an infusion of 1 mg/ml ropivacaine, 2 [mu]g/ml fentanyl, and 2 [mu]g/ml adrenaline, 10 ml/h during 48 h epidurally, and a placebo patient-controlled intravenous analgesia pump intravenously. Patients in group P received a patient-controlled intravenous analgesia pump with morphine intravenously and 10 ml/h placebo epidurally. Pain, the primary outcome variable, was measured using the numeric rating scale at rest (incision pain and "deep" visceral pain) and on coughing. Secondary outcome variables included gastrointestinal function, respiratory function, mobilization, and full recovery. Health-related quality of life was measured using the Short Form-36 questionnaire, and plasma concentration of fentanyl was measured in five patients to exclude a systemic effect of fentanyl.

Results: Incisional pain and pain on coughing were lower in group E compared with group P at 2-24 h, as was deep pain between 3 and 24 h postoperatively (P < 0.05). Maximum expiratory pressure was greater in group E at 4 and 24 h (P < 0.05) compared with group P. No difference in time to home discharge was found between the groups. The mean plasma fentanyl concentration varied from 0.2 to 0.3 ng/ml during 0-48 h postoperatively. At 1 month, the scores on emotional role, physical functioning, and general health of the Short Form-36 were higher in group E compared with group P. However, no group x time interaction was found in the Short Form-36.     

Thoracic epidural infusion for postoperative pain relief following abdominal aortic surgery: bupivacaine, fentanyl or a mixture of both?

Thirty patients who had undergone elective abdominal aortic surgery were studied in a prospective, randomised double-blind comparison of thoracic epidural 0.2% bupivacaine alone, thoracic epidural fentanyl alone and thoracic epidural 0.2% bupivacaine combined with fentanyl. Pain relief, pulmonary function, cardiovascular stability and side effects were assessed. Pain relief was excellent in the combined bupivacaine-fentanyl series, being significantly better than the other groups (p less than 0.05) during the entire study period and was not accompanied by hypotension. Forced expiratory parameters were reduced in all groups throughout the study to 50-60% of the pre-operative values, but there were no significant differences between groups. The incidence of side effects attributable to either epidural bupivacaine or fentanyl was low. This study supports the increasing use of epidural infusion analgesia for postoperative pain management after abdominal surgery.     

Combinations of Bupivacaine, Fentanyl, and Clonidine for Lumbar Epidural Postoperative Analgesia: A Novel Optimization Procedure

Background: The authors developed and applied a method to optimize the combination of bupivacaine, fentanyl, and clonidine for continuous postoperative lumbar epidural analgesia.

Methods: One hundred eighteen patients undergoing knee or hip surgery participated in the study. Postoperative epidural analgesia during 48 h after surgery was optimized under restrictions dictated by side effects. Initially, eight combinations of bupivacaine, fentanyl, and clonidine (expressed as drug concentration in the solution administered) were empirically chosen and investigated. To determine subsequent combinations, an optimization model was applied until three consecutive steps showed no decrease in pain score. For the first time in a clinical investigation, a regression model was applied when the optimization procedure led to combinations associated with unacceptable side effects.

Results: The authors analyzed 12 combinations with an allowed bupivacaine concentration range of 0-2.5 mg/ml, a fentanyl concentration range of 0-5 [mu]g/ml, and a clonidine concentration range of 0-5 [mu]g/ml. The best combinations of bupivacaine, fentanyl, and clonidine concentrations were 1.0 mg/ml-1.4 [mu]g/ml-0.5 [mu]g/ml, 0.9 mg/ml-3.0 [mu]g/ml-0.3 [mu]g/ml, 0.6 mg/ml-2.5 [mu]g/ml-0.8 [mu]g/ml, and 1.0 mg/ml-2.4 [mu]g/ml-1.0 [mu]g/ml, respectively, all producing a similarly low pain score. The incidence of side effects was low. The application of the regression model to combinations associated with high incidence of motor block successfully directed the optimization procedure to combinations within the therapeutic range.     

A randomized double-blind comparison of epidural versus intravenous fentanyl infusion for analgesia after thoracotomy

This study compared epidural and intravenous fentanyl infusions for pain relief for the first 20 h after thoracotomy, in order to examine whether an thoracic epidural fentanyl infusion offers clinical advantage over an intravenous infusion. Forty patients were assigned randomly to receive either fentanyl epidurally and saline intravenously or fentanyl intravenously and saline epidurally in a double-blind fashion. For each patient the fentanyl infusion was titrated to a rate required for pain relief (pain score less than 3, maximum 10). Patients reported similar median pain scores, but in the epidural group the required mean fentanyl infusion rate was less (0.95 +/- 0.23 vs. 1.67 +/- 0.46 micrograms.kg-1.h-1, P = 0.0001) and plasma fentanyl concentrations were less at 4 and 18 h (4 h: 0.81 +/- 0.27 vs. 1.38 +/- 0.36 ng.ml-1, P = 0.0001; 18 h: 0.94 +/- 0.32 vs. 1.54 +/- 0.65 ng.ml-1, P = 0.0007) than those in the intravenous group. Respiratory function was better preserved and the incidence of nausea and sedation was less in the epidural group than in the intravenous group. In conclusion there appears to be a clinical advantage to the epidural infusion over the intravenous infusion of fentanyl for analgesia after thoracotomy.     

Paravertebral ropivacaine, 0.3%, and bupivacaine, 0.25%, provide similar pain relief after thoracotomy

OBJECTIVE: This study was designed to determine whether ropivacaine plus fentanyl was as effective as bupivacaine plus fentanyl in a continuous thoracic paravertebral block after posterolateral thoracotomy. DESIGN: Patients were randomly assigned in a blinded fashion to receive 1 of 2 solutions for paravertebral analgesia. SETTING: Multi-institutional university hospital. PARTICIPANTS: Sixty patients undergoing elective thoracotomy. Interventions: A continuous paravertebral infusion of 0.1 mL/kg/h of either 0.3% ropivacaine/fentanyl, 3 microg/mL, or 0.25% bupivacaine/fentanyl, 3 microg/mL, was started on admission to the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Pain scores (rest, deep breathing, and coughing), spirometry, subcutaneous opioids, or nonsteroidal anti-inflammatory drug consumption and adverse events were assessed for 48 hours. Both techniques provided adequate pain relief for the first 2 days after posterolateral thoracotomy. There were no differences between groups in pain scores at rest, coughing, or movement. There was an improvement of spirometry values between the first and second day in both groups. There were no differences in the requirements for rescue analgesia and side effects between groups. CONCLUSIONS: It is concluded that both bupivacaine, 0.25%, and ropivacaine, 0.3%, with fentanyl are equally effective for post-thoracotomy pain control when used via continuous paravertebral blockade.     

Comparison of continuous epidural bupivacaine infusion plus either continuous epidural infusion or patient-controlled epidural injection of fentanyl for postoperative analgesia.

We compared the postoperative epidural analgesia provided by the continuous epidural infusion of bupivacaine supplemented with patient-controlled injection (PCA) of epidural fentanyl with that provided by a continuous infusion of bupivacaine supplemented with a continuous epidural infusion of fentanyl. Our patient population comprised 16 ASA physical status I or II patients undergoing laparotomy with a midline incision under general anesthesia combined with bupivacaine epidural analgesia. Post-operatively, a continuous epidural infusion of bupivacaine (0.1 mg.kg-1.h-1) was combined with epidural fentanyl given by either (a) PCA (15-micrograms bolus with a lockout interval of 12 min, n = 8) or (b) continuous infusion (1 microgram.kg-1.h-1, n = 8). In the case of inadequate pain relief in the latter group, the fentanyl infusion rate was increased by 10 micrograms/h. Analgesia evaluated by a visual analogue pain score and by a verbal pain score was similarly effective in both groups. The sedation score was also similar in both groups. The total dose of epidural fentanyl administered during the first 24 h was significantly lower in the PCA group than in the continuous infusion group (405 +/- 110 micrograms vs 1600 +/- 245 micrograms, P less than 0.001). The dose of fentanyl given during each 4-h interval ranged between 40 and 160 micrograms in the PCA group and 251 and 292 micrograms in the continuous infusion group. Clinically detectable respiratory depression was not observed in either group. In conclusion, epidural administration of 0.1 mg.kg-1.h-1 bupivacaine combined with fentanyl provides effective postoperative analgesia with a total dose of fentanyl required that is lower when fentanyl is administered by epidural PCA rather than by continuous epidural infusion.     

Postoperative analgesia with epidural bupivacaine and low-dose fentanyl - a comparison of two concentrations

Background : The purpose of the study was to compare the analgesic and side effects of two epidurally administered mixtures of bupivacaine and fentanyl with the same drug ratios.
Methods : One hundred patients scheduled for colorectal surgery were randomized to receive a thoracic epidural infusion of either bupivacaine 0.12% with fentanyl 2 μg/ml or bupivacaine 0.24% with fentanyl 4 μg/ml during 48 h postoperatively. The pumps were adjusted to keep the visual analogue scale (VAS) pain score at 3 or less (on a scale of 0–10) with a minimum of adverse effects.
Results : There were no statistically significantly differences between the two groups in VAS pain scores. The average VAS pain score resting varied between 0.5 and 1, and coughing between 1.9 and 3.4. One case of respiratory depression with breathing frequency 7 occurred in each group, but none of the patients required naloxone. One patient in the low concentration group developed partial motor weakness in both legs 36 h postoperatively. Equal drug amounts - bupivacaine 10.8–11 mg/h and fentanyl 18-18.4 μg/h - were given in both groups throughout the study.
Conclusions : Both groups had low pain scores with few and comparable adverse effects. It thus seems that the volume is not important when mixtures of bupivacaine and fentanyl in the studied concentrations are infused epidurally at a low thoracic level. Practical reasons favour the higher concentration mixture.     

Patient supplemented epidural analgesia after major abdominal surgery with bupivacaine/fentanyl or ropivacaine/fentanyl

PURPOSE: To compare analgesic efficacy and occurrence of motor block and other side effects during patient supplemented epidural analgesia (PSEA) with either ropivacaine/fentanyl or bupivacaine/fentanyl mixtures. METHODS: In a prospective, randomized, double-blind study, 32 ASAI-III patients undergoing major abdominal surgery received an epidural catheter at the T8- T10, followed by integrated general epidural anesthesia. Postoperative epidural analgesia was provided using a patient controlled pump with either ropivacaine 0.2%/2 microg x ml(-1) fentanyl (group Ropivacaine, n = 16) or bupivacaine 0.125%/2 microg x ml(-1) fentanyl (group Bupivacaine, n = 16) [background infusion 4-6 ml x hr(-1), 1.5 ml Incremental Doses and 20 min lock out]. Verbal pain rating score, number of incremental doses, consumption of epidural analgesic solution and rescue analgesics, sedation (four-point scale), and pulse oximetry were recorded by a blind observer for 48 hr after surgery. RESULTS: No differences in pain relief, motor block, degree of sedation, pulse oximetry and other side effects were observed between the two groups. The number of incremental doses and the volume of analgesic solution infused epidurally were higher in patients receiving the bupivacaine/fentanyl mixture (10 [0-52] I.D. and 236 [204-340] ml) than in patients receiving the ropivacaine/fentanyl solution (5 [0-50] I.D. and 208 [148-260] ml) (P = 0.03 and P = 0.05, respectively). CONCLUSION: Using a ropivacaine 0.2%/2 microg x ml(-1) fentanyl mixture for patient supplemented epidural analgesia after major abdominal surgery provided similar successful pain relief as bupivacaine 0.125%/2 microg x ml(-1) fentanyl, but patients receiving bupivacaine/fentanyl requested more supplemental.