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.     

The minimally effective concentration of adrenaline in a low-concentration thoracic epidural analgesic infusion of bupivacaine,fentanyl and adrenaline after major surgery. A randomized,double-blind,dose-finding study

BACKGROUND: We have documented that adrenaline 2.0 micro g.ml- 1 markedly improves relief of dynamic pain when added to a thoracic epidural analgesic infusion of bupivacaine 1 mg.ml- 1 and fentanyl 2 micro g.ml- 1. Concern about possible adverse effects on spinal cord blood flow, expressed by others, prompted us to find the lowest concentration of adrenaline needed to produce effective and reliable pain relief after major surgery. METHODS: A prospective, randomized, double-blind, parallel group study was carried out in 36 patients after major thoracic or upper abdominal surgery. Patients with only mild pain when coughing during titrated thoracic epidural infusion of approximately 9 ml per hour of bupivacaine 1 mg.ml- 1, fentanyl 2 micro g.ml- 1, and adrenaline 2.0 micro g.ml- 1 were included. The study was conducted as a dose-finding study comparing three different adrenaline concentrations in the epidural mixture (0.5, 1.0, and 1.5 micro g.ml- 1) with each other and with adrenaline 2.0 micro g.ml- 1 in our standard epidural mixture. On the 1st postoperative day, the patients were randomly allocated into three equal groups of 12 patients each, and given a double-blind epidural infusion at the same rate, but with different adrenaline concentrations (0.5, 1.0, or 1.5 micro g.ml- 1). The effects were observed for 4 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 per hour (4 ml) and subsequent i.v. morphine, if necessary. All patients received rectal paracetamol 1 g, every 6th hour. Main outcome measures were pain intensity at rest and when coughing, evaluated by a visual analogue scale and an overall quality of pain relief score. The extent of sensory blockade was evaluated by determining dermatomal hypaesthesia to cold. RESULTS: Pain intensity when coughing increased (P < 0.001) and the number of hypaesthetic dermatomal segments decreased (P < 0.002) when the concentration of adrenaline was reduced below 1.5 micro g.ml- 1 in the triple epidural mixture. This change started within two hours after reducing the concentration of adrenaline below 1.5 micro g.ml- 1. The differences in pain intensities at rest were less pronounced. After 4 h with adrenaline 0.5 or 1.0 micro g.ml- 1 pain intensity when coughing was unacceptable in spite of rescue analgesia. After restarting the standard epidural mixture with adrenaline 2.0 micro g.ml- 1, pain intensity was again reduced to mild pain when coughing and the sensory blockade was restored. Occurrence of pruritus increased with a decreasing adrenaline concentration. CONCLUSIONS: Adrenaline in a dose-related manner improves the pain-relieving effect and sensory blockade and decreases the occurrence of pruritus of a low-concentration thoracic epidural analgesic infusion of bupivacaine 1 mg. ml- 1 and fentanyl 2 micro g.ml- 1 after major thoracic or upper abdominal surgery. The minimally effective concentration of adrenaline, when added to bupivacaine 1 mg.ml- 1 and fentanyl 2 micro g.ml- 1, to maintain relief of dynamic pain is approximately 1.5 micro g.ml- 1. The data clearly document that dynamic, cough-provoked pain is a more sensitive outcome measure for postoperative pain relief than pain at rest.     

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.     

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.     

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.