Analgesic effects of interpleural bupivacaine with fentanyl for post-thoracotomy pain

Analgesic Effects of Interpleural Bupivacaine With Fentanyl for Post-thoracotomy Pain ¨ zkan, MD,* Sedat Demircan, MD,† Umut Go¨k, MD,* Deniz Karakaya, MD,* Sibel Baris, MD,* Fatih O ¨ Emre Ustu¨n, MD,* and Ayla Tu¨r, MD* Objective: The analgesic effect of bupivacaine/fentanyl with epinephrine given interpleurally after thoracotomy was investigated in a randomized placebo and intravenous controlled study. Design: Prospective clinical study. Setting: University teaching hospital. Participants: Sixty American Society of Anesthesiologists physical status II and III patients scheduled for posterolateral thoracotomy with general anesthesia. Interventions: Patients were randomly divided into 4 groups to receive either 0.5% bupivacaine/1.5 ␮g/kg of fentanyl with 5 ␮g/mL of epinephrine (n ⴝ 15, group IPBF), 0.5 % bupivacaine with 5 ␮g/mL of epinephrine (n ⴝ 15, group IPB), or saline (n ⴝ 15, group IPS) in a total volume of 15 to 20 mL in 60 seconds by an interpleural catheter placed at the end of surgery by direct vision. The same volume of bupivacaine 0.25% and 1.5 ␮g/kg of fentanyl with 5 ␮g/mL of epinephrine to group IPBF, bupivacaine 0.25% with 5 ␮g/mL of epinephrine to group IPB or saline to group IPS was injected through the interpleural catheter every 6 hours for 48 hours postoperatively. Intravenous fentanyl (n ⴝ 15, group IVF) and interpleural saline groups received 1.5 ␮g/kg of fentanyl intravenously at the first complaint of pain. All patients also received patient-controlled analgesia (PCA)

with fentanyl for 48 hours postoperatively. Metamizol sodium was used as a rescue analgesic. Measurements and Main Results: Adequacy of pain relief was evaluated with the “Prince Henry Pain Scale” and visual analog pain scale. Fentanyl consumption via PCA and complications were evaluated for 48 hours. Visual analog scale scores were significantly higher in the interpleural saline group at 4 and 12 hours (6.6 ⴞ 1.2 and 5.0 ⴞ 2.1, respectively) postoperatively. Significantly more patients in the IPBF group had lower pain scores during coughing and deep breathing. Fentanyl consumption via PCA device was significantly higher in the intravenous fentanyl group (1,069 ⴞ 96.9 ␮g) than the interpleural groups (577.3 ⴞ 72.2 ␮g, 651.1 ⴞ 61.9 ␮g, and 601.0 ⴞ 22.6 ␮g in IPBF, IPB, and IPS groups, respectively). Conclusion: It is concluded that total fentanyl consumption via PCA decreased in all interpleural groups, but pain during coughing and deep breathing was significantly reduced in only the interpleural bupivacaine/fentanyl with epinephrine group. © 2004 Elsevier Inc. All rights reserved.

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caine and fentanyl combination for post-thoracotomy pain management was determined.

OST-THORACOTOMY PAIN IS very severe, and the intensity of pain is exacerbated by ventilation. Limited ventilation may cause atelectasis, hypoxia, and pulmonary infection.1 Effective analgesia provides early mobilization after surgery and reduces morbidity. A variety of agents and techniques have been shown to be effective for post-thoracotomy pain.1 These include systemic opioids, non-steroidal anti-inflammatory drugs (NSAID), and regional analgesia including epidural, spinal, intercostals, and interpleural techniques. Systemic opioids are the most commonly used techniques to prevent post-thoracotomy pain, but it results in adverse effects such as respiratory depression, somnolence, nausea, and vomiting. The combination of opioids and local anesthetics through a thoracic epidural catheter is the most effective method for post-thoracotomy pain.2 However, considerable experience is required for thoracic epidural analgesia, and it is not suitable in patients with coagulation disorders, receiving anticoagulant therapy, spinal deformities, neurologic disorders, or patients converted from thoracoscopy to open thoracotomy. Several studies with local anesthetics alone have shown that interpleural analgesia improved analgesic efficacy for post-thoracotomy pain,3-5 whereas others have not demonstrated any improvement.6-8 Since the demonstration of opioid receptors in the peripheral nervous system,9 numerous studies have been performed. It was shown that a fentanyl and bupivacaine combination provided superior analgesia to bupivacaine alone for axillary brachial plexus block.10 In addition, 20 mg of interpleural morphine achieved better analgesia than the same dose of morphine administered intravenously for post-thoracotomy pain, and this effect was attributed to peripheral effects of morphine.11 In the present study, the analgesic efficacy of an interpleural bupiva-

KEY WORDS: posterolateral thoracotomy, interpleural analgesia, bupivacaine, fentanyl, intravenous analgesia

PATIENTS AND METHODS After obtaining local medical ethics committee approval and informed patient consent, 60 patients, American Society of Anesthesiologists physical status II to III, aged 19 to 76 years, undergoing elective lobectomy through a posterolateral thoracotomy were studied. Exclusion criteria included patients who have shown allergic reactions to local anesthetics, drug abuse, obesity (weight greater than 100 kg), significant central nervous system, hepatic, or renal disease; who are undergoing pleurectomy; and who have pneumonia, empyema, or known pleuritis. Patients were randomized according to their participation to the study and divided equally into four groups with 15 patients in each group. Because of the presence of an intravenous opioid group (no interpleural catheter), it was impossible to double blind the study. However, study design was blinded between interpleural groups. All interpleural solutions were prepared by an anesthesiologist blinded to the group allocation. Patients received 40 mg of famotidine and 10 mg of diazepam orally 1 hour before surgery for premedication. Anesthesia was induced with 2.5 mg/kg of propofol and 1.5 ␮g/kg of fentanyl. Rocuronium, 0.6 mg/kg, was given for neuromuscular relaxation, and the trachea was intubated and the lungs ventilated mechanically. Anesthesia was main-

From the Departments of *Anesthesiology and †Thoracic Surgery, Ondokuz Mayis University, Samsun, Turkey. ¨ niAddress reprint requests to Deniz Karakaya, Ondokuz Mayıs U versitesi, Tıp Faku¨ltesi, Anesteziyoloji ve Reanimasyon, Anabilim Dali, 55139, Kurupelit, Samsun, Turkey. E-mail: [email protected] © 2004 Elsevier Inc. All rights reserved. 1053-0770/04/1804-0013$30.00/0 doi:10.1053/j.jvca.2004.05.026

Journal of Cardiothoracic and Vascular Anesthesia, Vol 18, No 4 (August), 2004: pp 461-465

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Table 1. Prince Henry Pain Scale Score

Definition

0 1 2 3 4

No pain on coughing Pain on coughing but not on deep breathing Pain on deep breathing but not at rest Slight pain at rest Severe pain at rest

tained with isoflurane and nitrous oxide in oxygen. If analgesia was inadequate (if blood pressure and heart rate exceeded 20% of the preoperative values), 1.5 ␮g/kg of fentanyl was given intravenously during the intraoperative period. Surgery was performed via a standard posterolateral thoracotomy; all incisions were made in the posterior fifth intercostal space. A radial artery was cannulated for blood gases sampling. At the end of the surgery, just before chest closure, the surgeon inserted a 16-G interpleural catheter by direct visual observation in group 1 (group IPBF), 2 (group IPB), and 3 (group IPS). The tip of the catheter was placed toward the fourth or fifth intercostal space, and all catheter tips were sutured loosely to the posterior parietal pleura. The IPBF group patients were given 0.5% bupivacaine and 1.5 ␮g/kg of fentanyl with 5 ␮g/mL of epinephrine (EPI); and group IPB patients received 0.5% bupivacaine with 5 ␮g/mL of EPI in a total volume of 15 to 20 mL (15 mL for 50-55 kg, 16 mL for 56-60 kg, 17 mL for 61-65 kg, 18 mL for 66-70 kg, 19 mL for 71-75 kg, and 20 mL for greater than 75 kg) in 60 seconds at the first complaint of pain. The group IPS patients received 1.5 ␮g/kg of fentanyl intravenously and then the same volume of saline through the interpleural catheter at first complaint of pain. Thereafter, the same volume of 0.25% bupivacaine and 1.5 ␮g/kg of fentanyl with 5 ␮g/mL of EPI to group IPBF, 0.25% bupivacaine with 5 ␮g/mL of EPI to group IPB, and saline to group IPS were injected through the interpleural catheter every 6 hours for 48 hours postoperatively. The chest tubes were clamped for 20 minutes after instillation of the solutions. Group IVF patients received 1.5 ␮g/kg of fentanyl intravenously at first complaint of pain. Before the injection of interpleural drugs, the patients were positioned supine and placed in this position during the chest tube closure period. All groups received intravenous patient-controlled analgesia (PCA) with fentanyl (10-␮g bolus dose, lockout 10 minutes, maximum of 200 ␮g in 4 hours, no loading, and background infusion) with a PCA device (Abbott Pain Management Provider; Abbott Laboratories, North Chicago, IL) for 48 hours postoperatively. If analgesia was inadequate and visual analog score (VAS) remained greater than 5 for 30 minutes, 1 g of metamizol sodium was given intramuscularly. Recorded parameters were mean arterial pressure, heart rate, arterial blood gases, respiratory rate, peripheral oxygen saturation (SpO2) preoperatively, in the recovery room, at 4, 12, 24, and 48 hours after

operation. Patients received oxygen at 4 L/min with a face mask in the recovery room and for 12 hours postoperatively. Postoperative pain was assessed by a VAS using a 10-cm linear analog scale at rest and with “Prince Henry Pain Scale” (PHPS) (Table 1). 12 VAS and PHPS were evaluated at 4, 8, 12, 24, and 48 hours after surgery. Level of sedation was evaluated with a 5-point scale (1 ⫽ spontaneous communication, not sleepy; 2 ⫽ spontaneous communication, slightly asleep; 3 ⫽ no spontaneous communication, responds to verbal commands; 4 ⫽ only responds to physical contact; 5 ⫽ no response to even physical contact) at 1, 4, 8, 12, 24, and 48 hours postoperatively. The highest sedation scores during the study were included in the data analysis. SpO2 was continuously monitored during the postoperative period. Fentanyl consumption with the PCA device, additional analgesic requirements, side effects, hypotension, pruritis, sedation, nausea, emesis, and length of stay in the hospital were recorded. Demographic data were analyzed using analysis of variance or the chi-square test as appropriate. Mean arterial pressure, heart rate changes, blood gases, and drug requirements were compared by using analysis of variance with repeated measures. Categorical data were analyzed using the chi-square and Fisher exact test. Data are presented as mean ⫾ standard error of the mean and median (range) for parametric or nonparametric data. A p value ⬍0.05 was considered significant. RESULTS

Demographic data and duration of anesthesia were similar in all groups (Table 2). Duration of hospitalization was shorter in group IPB than groups IPBF and IVF (p ⬍ 0.05). Total fentanyl consumption during the intraoperative period was comparable in all groups. Mean arterial blood pressure and heart rate values were within normal limits in all groups during the study period. There were no significant differences in all groups with respect to arterial blood gases and SpO2 values. The IPS group had the highest VAS score at 4 hours postoperatively (p ⬍ 0.05). VAS scores were significantly higher in groups IPS and IVF than IPBF and IPB groups at 12 hours postoperatively (p ⬍ 0.05) (Fig 1). The number of patients who have PHPS ⱕ1 and ⱖ2 was shown in Table 3. Patients in group IPBF had lower PHPS scores than the other groups throughout the study period, reaching significance at 4, 8, 24, and 48 hours versus group IPS. In addition, the number of patients with PHPS ⱕ1 was higher in group IPBF than IPB and IVF groups at 8 hours postoperatively (p ⬍ 0.05). Also, more patients had lower PHPS scores at 12 hours in group IPBF.

Table 2. Demographic Data, Duration of Anesthesia (Mean ⴞ Standard Error of the Mean), and Length of Stay in Hospital (Median [Range]) of Groups

Age (y) Sex (F/M) Weight (kg) Height (cm) Duration of anesthesia (min) Intraoperative fentanyl (␮g) Length of stay in hospital (day) Abbreviations: F, female; M, male. *p ⬍ 0.05 in group IPB versus IPBF and IVF.

Group IPBF

Group IPB

Group IPS

Group IVF

57.9 ⫾ 3.0 5/10 68.3 ⫾ 2.3 163.0 ⫾ 1.9 222.0 ⫾ 26.3 263.3 ⫾ 80.3 10 (8-15)

41.1 ⫾ 5.2 4/11 68.0 ⫾ 3.9 167.0 ⫾ 2.3 180.5 ⫾ 14.6 256.6 ⫾ 71.8 8 (5-48)*

48.7 ⫾ 5.2 5/10 66.6 ⫾ 3.0 163.1 ⫾ 2.2 197.7 ⫾ 17.4 251.5 ⫾ 70.1 9 (5-27)

54.0 ⫾ 4.1 5/10 71.5 ⫾ 2.6 162.3 ⫾ 2.0 198.0 ⫾ 16.3 271.6 ⫾ 65.4 10 (7-35)

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Fig 1. VAS scores of all groups (mean ⴞ standard deviation); *p < 0.05 in group IPS versus groups IPBF, IPB, and IVF. **p < 0.05 in groups IPS and IVF versus groups IPBF and IPB.

Fentanyl consumption with the PCA device is shown in Figure 2. Fentanyl consumption during 12 to 24 hours, 24 to 48 hours, and cumulative PCA drug consumption at the end of the study were significantly higher in the group IVF than the interpleural groups. There was no statistically significant difference for fentanyl consumption via PCA between interpleural groups over any time. Additional analgesic requirement was recorded for 2 patients in group IPBF, 3 in IPB, 6 in IPS, and 5 in IVF. There were no significant differences between groups with respect to additional analgesic requirement. Peripheral oxygen saturation decreased ⬍94% only in 1 patient who experienced atelectasis in the postoperative period in group IPS. Patients were scored between 1 to 3 for sedation during the study period. There was no difference in sedation scores between the groups at any time postoperatively. Highest level of sedation scores and other complications were shown in Table 4. DISCUSSION

Interpleural injection of 15 to 20 mL of 0.5% bupivacaine with 1.5 ␮g/kg of fentanyl and 5 ␮g/mL of EPI (followed by Table 3. Number of Patients Having “Prince Henry Pain Scale” <1/>2

4.h 8.h 12.h 24.h 48.h

Group IPBF

Group IPB

Group IPS

Group IVF

6/9* 11/4† 10/5‡ 11/4* 12/3*

4/11 4/11 5/10 7/8 7/8

1/14 4/11 5/10 5/10 3/12

3/12 3/12 4/11 6/9 10/5

*p ⬍ 0.05 versus group IPS. †p ⬍ 0.05 versus groups IPB, IPS, and IVF. ‡p ⬍ 0.05 versus group IVF.

0.25% bupivacaine/1.5 ␮g/kg of fentanyl with 5 ␮g/mL of EPI at 6-hour intervals) significantly reduced pain during coughing and deep breathing after thoracotomy. Patients who received interpleural drug injection also had significantly reduced PCA fentanyl consumption. During posterolateral thoracotomy, many muscles are either cut or retracted. The intercostal nerves may be damaged by retraction of ribs, sutures, or wires passing around ribs. All these procedures with soft-tissue inflammation and visceral damage cause considerable pain. Pain is exacerbated by movement and by coughing. Because of shallow breathing and coughing inability after thoracotomy, and even after upper abdominal surgery, lung compliance is reduced, leading to atelectasis of some lung areas, ventilation/perfusion mismatches and hypoxemia. Effective analgesia allows the patient to take deep breaths, cough effectively to clear secretions, and prevent hypoxemia. In recent years, thoracic epidural analgesia has gained popularity for post-thoracotomy pain management, but it is not suitable in patients with coagulation disorders, spinal deformities, and neurologic disorders, or those receiving anticoagulant therapy.2 Interpleural analgesia is another technique for post-thoracotomy pain management, and an interpleural catheter can be easily placed by direct vision during thoracotomies without the inherent risk of thoracic epidural blockade. This technique is also suitable when a patient is scheduled for a thoracoscopic procedure, where no epidural catheter is used, and later the surgeon converts the thoracoscopic procedure into an open mini-thoracotomy or open thoracotomy. Local anesthetics have been used through interpleural catheters in several studies, but the results are controversial. Silomon et al6 and Schneider et al7 reported no difference in analgesic requirements between patients treated with interpleural bupivacaine or saline solutions.

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Fig 2. Total fentanyl consumption via PCA in all groups (mean ⴞ standard deviation). *p < 0.05 versus IPBF and IPS. **p < 0.001 versus IPBF and IPS; ***p < 0.05 versus IPBF, IPB, and IPS; ␦p < 0.01 versus IPB, #p < 0.05 versus IPB.

In contrast, Mann et al5 reported no difference in opioid consumption but reduced VAS pain scores with interpleural 0.25 % bupivacaine. Similarly, Ohlmer et al4 found that patients who had interpleural analgesia with 0.25% bupivacaine and intercostal blocks had significantly reduced opioid demand after thoracotomy than those who had intravenous opioid. The reason for the variable results may be because of different study design (retrospective v prospective), different concentrations and volumes of the solutions, differences in chest tube clamping protocols, different catheter tip position, the use of different pain evaluation scores, and surgery type. Opioids are the mainstay of analgesic regimen for postthoracotomy pain, but which route is the most suitable is controversial. Respiratory depression is the most severe complication of systemic opioid use. Additionally, pruritis and prolonged nausea/vomiting are the other complications of systemic opioids. Since the demonstration of opioid receptors in the peripheral nerves,9 there has been a great deal of interest in the combination of local anesthetics and opioids to improve the quality of nerve blocks. Aykac et al11 showed better analgesia with 20 mg of interpleural morphine than the same dose of intravenous morphine. This effect may be attributable to pe-

Table 4. Complications (Number of Patients) and Sedation Scores (Median [Range]) of All Groups

Incisional infection Air leak from chest tube Atelectasis Pleural effusion Problems in blood glucose regulation Pruritis (mild) Sedation

Group IPBF

Group IPB

Group IPS

Group IVF

0 0 0 1

1 0 0 0

2 1 1 0

4 1 0 0

1 1 1 (1-3)

0 0 1 (1-2)

0 0 1 (1-3)

0 0 1 (1-3)

ripheral effects of morphine. In contrast to this study, Welte et al13 showed that 2.5 mg of interpleural morphine did not reduce post-thoracotomy pain intensity. However, the dose of morphine was quite low in that study for sufficient analgesia. The present study suggested that addition of fentanyl to bupivacaine will improve analgesia after thoracotomy. To the best of the authors’ knowledge, interpleural opioid and local anesthetic combinations have not been used for post-thoracotomy pain. In this study, addition of fentanyl to bupivacaine interpleurally did not reduce total fentanyl consumption via PCA with respect to the other interpleural groups. However, the quality of analgesia during coughing or deep breathing was significantly better with the interpleural bupivacaine and fentanyl combination than interpleural bupivacaine, saline, and systemic opioid alone. Fentanyl consumption via PCA was higher in the intravenous fentanyl group than all the interpleural groups, reaching significance after 12 hours postoperatively. Increasing analgesic consumption 12 hours after operation may be the result of patient mobilization and encouragement for coughing. A disadvantage of thoracostomy tube clamping is the risk of pneumothorax in patients with a large air leak. However, unclamping of the chest tube results in more rapid removal of the injected solution from the pleural cavity.14 It was reported in several studies that interpleural bupivacaine provided sufficient analgesia after cholecystectomy when loss of local anesthetics did not occur.1,15,16 The authors clamped the chest tube for 20 minutes after local anesthetic injection in the supine position under strict observation and did not observe any complication during the clamping period. The surgical procedures (lung resection, lobectomy, and so on) performed during thoracotomy decrease total lung capacity related to the amount of lung tissue resected. Interpleural local anesthetics also have effects on phrenic nerve and diaphragmatic function.17 Therefore, postoperative pulmonary function

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465

tests are influenced by the type of the surgery and by the effects of interpleural local anesthetics. For these reasons, postoperative pulmonary function tests were not investigated in the present study. In this study, PHPS score was used for determining pain during coughing and deep breathing. The more common postoperative complications after thoracotomy are because of limited ventilation and inadequate coughing. The combination of scale “0” and “1” in PHPS evaluates minimal discomfort for postoperative thoracotomy patients. On the other hand, postoperative complications may occur more commonly in patients with higher PHPS scores (scores 2, 3, and 4). In the IPBF group, more patients had lower PHPS scores throughout the study. Although VAS pain scores were high for the first 12 hours postoperatively in interpleural saline and intravenous fentanyl groups, PCA fentanyl consumption was low during this period in these groups. This may be because of ineffective use of PCA devices by patients as a consequence of postoperative residual

effects of anesthesia. It may be expected that fentanyl consumption via PCA should be similar in IPS and IVF groups, but it was lower in the IPS group. Infusion of any kind of solution into the interpleural space may reduce rubbing between parietal and visceral pleura, and this effect may reduce pain during patient movement. The rate of postoperative complications was low in the interpleural bupivacaine group; therefore, the hospital length of stay was shorter in this group. Most of these complications were consequences of surgery. Only pruritis, which was seen only in 1 patient in the IPBF group, may be related to PCA fentanyl infusion. In conclusion, this study shows that fentanyl consumption via PCA was reduced with interpleural catheters regardless of the injected solution. However, administration of bupivacaine/ fentanyl with EPI combination through the interpleural catheter provides much better analgesia during coughing or deep breathing.

REFERENCES 1. Vade Boncouer TR: Interpleural regional analgesia, in Ferrante FM, Vade Boncouer TR (eds): Postoperative Pain Management. New York, NY, Churchill Livingstone, 1993, pp 383-402 2. Savage C, McQuitty C, Wang D, et al: Postthoracotomy pain management. Chest Surg Clin North Am 12:251-263, 2002 3. Inderbitzi R, Flueckiger K, Ris HB: Pain relief and respiratory mechanics during continuous intrapleural bupivacaine administration after thoracotomy. Thorac Cardiovasc Surg 40:87-89, 1992 4. Ohlmer A, Leger R, Scheiderer U, et al: Pain therapy after thoracotomies—Systemic patient-controlled analgesia (PCA) with opioid versus intercostal block and interpleural analgesia. Anaesthesiol Reanim 22:159-163, 1997 5. Mann LJ, Young GR, Williams JK, et al: Intrapleural bupivacaine in the control of postthoracotomy pain. Ann Thorac Surg 53:449-454, 1992 6. Silomon M, Claus T, Huwer H, et al: Interpleural analgesia does not influence postthoracotomy pain. Anesth Analg 91:44-50, 2000 7. Schneider RF, Villamena PC, Harvey J, et al: Lack of efficacy of interpleural bupivacaine for postoperative analgesia following thoracotomy. Chest 103:414-416, 1993 8. Rosenberg PH, Scheinin BM, Lepantalo MJ, et al: Continuous intrapleural infusion of bupivacaine for analgesia after thoracotomy. Anesthesiology 67:811-813, 1987

9. Stein C: Peripheral mechanisms of opioid analgesia. Anesth Analg 76:182-191, 1993 10. Karakaya D, Buyukgoz F, Baris S, et al: Addition of fentanyl to bupivacaine prolongs anesthesia and analgesia in axillary brachial plexus block. Reg Anesth Pain Med 26:434-438, 2001 11. Aykac B, Erolcay H, Dikmen Y, et al: Comparison of intrapleural versus intravenous morphine for postthoracotomy pain management. J Cardiothorac Vasc Anesth 9:538-540, 1995 12. Torda TA, Pybus DA: Extradural administration of morphine and bupivacaine. A controlled comparison. Br J Anaesth 56:141-146, 1984 13. Welte M, Haimerl E, Groh J, et al: Effect of interpleural morphine on postoperative pain and pulmonary function after thoracotomy. Br J Anaesth 69:637-639, 1992 14. Ferrante FM, Chan VW, Arthur GR, et al: Interpleural analgesia after thoracotomy. Anesth Analg 72:105-109, 1991 15. Laurito CE, Kirz LI, Vade Bancouer TR, et al: Continuous infusion of interpleural bupivacaine maintains effective analgesia after cholecystectomy. Anesth Analg 72:516-521, 1991 16. Stromskag KE, Reiestad F, Holmqvist EL, et al: Intrapleural administration of 0.25%, 0.375%, and 0.5% bupivacaine with epinephrine after cholecystectomy. Anesth Analg 67:430-434, 1988 17. Covino BG: Interpleural regional analgesia. Anesth Analg 67: 427-429, 1988