Bupivacaine

Intrapleural bupivacaine has been reported to be effective for analgesia following cholecystectomy and thoracic surgery. Twenty patients who had a posterolateral thoracotomy were studied in a randomized, double-blind, placebocontrolled fashion. Patients were assigned to receive intrapleural administration of either 0.5 percent bupivacaine or saline solution every 4 h for 12 doses postoperatively, as well as narcotic analgesics as needed for additional pain control. Pain was assessed using a visual analogue scale. Narcotic analgesic use, duration of hospitalization, and the development of complications were recorded. There were nine evaluable patients who received bupivacaine, and ten patients who received placebo. The age, sex, and type of operation were similar in the two groups, and the procedures were performed by the same two surgeons. The mean pain score at 24 h postoperatively was 5.8 [+ or -] 0.8 in the bupivacaine group and 6.0 [+ or -] 0.6 in the placebo group. At 48 h, the scores were 4.6 [+ or -] 0.8 in the bupivacaine group and 5.1 [+ or -] 0.9 in the placebo group. The mean dose of morphine sulfate or equianalgesic dose of meperidine during the first 24 h was 13.9 [+ or -] 3.7 mg in the bupivacaine group and 12.6 [+ or -] 1.8 mg in the placebo group, and during the next 24 h it was 40.0 [+ or -] 13.4 mg in the bupivacaine group and 38.0 [+ or -] 9.2 mg in the placebo group. The mean duration of hospitalization was 12.8 [+ or -] 3.2 days in the bupivacaine group and 12.1 [+ or -] 2.9 days in the placebo group. Two patients who received bupivacaine and three patients who received placebo had development of pneumonia or atelectasis postoperatively. There was no statistically significant difference in any parameter between those who received bupivacaine and those who received placebo. Thus, there was no subjective or objective clinical benefit of this method of postoperative analgesia compared with placebo following posterolateral thoracotomy.

Pain relief reduces postoperative complications, especially following thoracotomy or upper abdominal surgery. Inability to breathe deeply or to cough due to pain after surgery can lead to atelectasis, retention of secretions, pneumonia, and inability to sustain unassisted ventilation.[1] Intramuscular or intravenous narcotic analgesics are usually used to control pain, and the benefits of pain control may be offset by adverse effects, including depression of ventilation, altered state of consciousness, decreased effectiveness of cough, and hypotension. For these reasons, alternative methods of pain control following surgery have been sought for many years.

In 1984, Kvalheim and Reistad[2] first described a technique of intrapleural injection of the local anesthetic agent bupivacaine for postoperative analgesia. Since that time, several studies have reported its effectiveness, and only one failed to demonstrate efficacy in postoperative patients.[2-11] Two of these studies had a randomized, controlled, and double-blinded design, and demonstrated the benefit of using intrapleural bupivacaine in patients following cholecystectomy (thoracotomy patients were not included)[10] and in thoracotomy patients in a very recently published study.[12]

In this study, intrapleural bupivacaine for postoperative analgesia was compared with placebo following thoracotomy in a randomized, double-blind trial.

METHODS

This study was approved by the Institutional Review Board of Beth Israel Medical Center, New York. Informed consent for participation was obtained from 20 patients who were admitted for thoracotomy to the Thoracic Surgery Service between January and November, 1991. They were randomly assigned to receive 30 ml of 0.5 percent intrapleural bupivacaine or 30 ml of intrapleural saline solution placebo through an additional intrapleural catheter placed during surgery, every 4 h for 12 doses, distributed by the pharmacy, identified by a code known only to the pharmacy. All patients received narcotic analgesia with morphine sulfate or meperidine at their request. Following injection of the study drug, chest tube suction was discontinued for 30 min, and then restarted. Patients with evidence of active infection of the pleural surface were excluded to avoid the possibility of enhanced systemic absorption of bupivacaine thought to be responsible for a seizure noted in one patient in the literature.[7] Pain scores were recorded in both groups at 24 and 48 h following surgery using a visual analogue pain scale described previously.[8,9] The scale consists of a 10-cm line demarcated at 1-cm intervals from 0 to 10 and anchored at each end with the words "no pain" and "most severe pain," respectively. A difference of three points on the visual analogue scale in either direction was considered clinically significant. The use of additional pain medication recorded as milligrams of morphine sulfate or equianalgesic dose of meperidine (75 mg of meperidine = 10 mg of morphine sulfate[13]) was noted, as well as complications such as pneumonia and atelectasis and the length of hospital stay. Results are presented as the mean [+ or -] SEM and compared using Student's t tests and Fisher's Exact Test. [TABULAR DATA OMITTED]

RESULTS

There were ten patients in the bupivacaine group and ten patients in the placebo group (Table 1). Of these 20 patients, one was excluded from the bupivacaine group after refusing the drug following three doses due to her belief that the medication was responsible for her dry mouth. Two more patients in the bupivacaine group and one patient in the placebo group received only six doses of the study drug; their results are not included in the analysis at 48 h. There were five male and four female patients in the bupivacaine group and five male and five female patients in the placebo group. The mean age was 58.3 [+ or -] 4.7 years in the bupivacaine group and 63.2 [+ or -] 3.0 years in the placebo group, which was not significantly different. All patients underwent posterolateral thoracotomy performed by the same two surgeons.

The mean pain score of the patients at 24 h postoperatively was 5.8 [+ or -] 0.8 in the bupivacaine-treated group and 6.0 [+ or -] 0.6 in the placebo-treated group. The mean pain score of the patients at 48 h postoperatively was 4.6 [+ or -] 0.8 in the bupivacaine-treated group and 5.1 [+ or -] 0.9 in the placebo-treated group. There was no statistically significant difference at 24 or 48 h.

The mean use of morphine sulfate or equianalgesic dose of meperidine during the first 24 h was 13.9 [+ or -] 3.7 mg in the bupivacaine-treated group and 12.6 [+ or -] 1.8 mg in the placebo-treated group. The mean use of morphine sulfate or equianalgesic dose of meperidine during the next 24 h postoperatively was 40.0 [+ or -] 13.4 mg in the bupivacaine-treated group and 38.0 [+ or -] 9.2 mg in the placebo-treated group. There was no statistically significant difference for the first or second 24-h period.

The mean duration of hospitalization was 12.8 [+ or -] 3.2 days in the bupivacaine-treated group and 12.1 [+ or -] 2.9 days in the placebo-treated group, which was not statistically significant.

The patients had similar indications for surgery and similar operative procedures in both groups. Two patients in the bupivacaine group and three patients in the placebo group had pneumonia or atelectasis (Table 1). This was not statistically significant using Fisher's exact test.

DISCUSSION

Compared with placebo, intrapleural injection of 30 ml of 0.5 percent bupivacaine at 4-h intervals following lateral or posterior thoracotomy was no different with regard to subjective assessment of pain by the patients, use of additional opiate analgesics, postoperative atelectasis or pneumonia, or duration of hospitalization. Other than in one patient who attributed a "dry mouth" to bupivacaine, there were no untoward effects related to the drug or placement of the additional catheter.

In 1984, Kvalheim and Reistad[2] described a technique of introducing bupivacaine into the pleural space with a catheter in 30 patients who underwent renal, breast, or gallbladder surgery. None of these patients requested supplemental narcotics for pain relief, and there were no untoward effects of the procedure noted.[2]

El-Naggar et al[6] studied 50 patients undergoing cholecystectomy who were treated postoperatively with intrapleural bupivacaine with adequate pain relief and no adverse effects of the technique or the drug.

Seltzer et al[7] treated 11 patients undergoing cholecystectomy with intrapleural bupivacaine postoperatively for pain control, which was achieved in 10 of 11 patients. Focal seizure activity within 1 min of injection of bupivacaine was noted in a patient under general anesthesia with presumed pleural inflammation, believed to cause an excessively high serum concentration of bupivacaine.[7]

In a randomized, double-blind comparison of the effects of intrapleural bupivacaine versus placebo in cholecystectomy patients, VadeBoncouer et al[10] demonstrated reduced patient-controlled morphine analgesia requirements, as well as a favorable effect on [FEV.sub.1] and FVC. Kambam et al[3] studied 24 patients undergoing thoracic surgery who received postoperative intrapleural bupivacaine for pain relief, which was effective in patients undergoing lateral and posterior thoracotomy, but not anterior thoracotomy.

In two separate studies, McIlvaine et al[4,5] treated 38 children undergoing thoracotomy with postoperative intrapleural bupivacaine. Adequate pain relief was achieved without complications or toxic reactions. In two patients who were placed in a supine position, 15[degrees] head down to reestablish anesthesia following a 1-h period of sitting up, reversible miosis and ptosis suggestive of a Horner's syndrome and blockade of the stellate ganglion developed along with return of analgesia.[4,5]

A study by Rosenberg et al[11] produced contrary results, where intrapleural administration of bupivacaine was not satisfactory to manage postoperative pain after thoractomy in 14 patients.

To our knowledge, this is the only prospective, randomized, double-blind, placebo-controlled study other than a study published only in abstract form and a very recently published study, to assess the usefulness of this method of analgesia in patients following thoracotomy.[12,14] Most previous trials in patients following thoracotomy are limited by lack of placebo control. In the recent study by Mann et al,[12] the authors reported significantly lower pain scores recorded 20 min after each dose of bupivacaine or placebo and smaller total number of milligrams of narcotics used in the bupivacaine group. The total number of milligrams per kilogram of body weight, however, was not significantly different between the two groups. It is possible that this study recognized the short-term analgesic effect of bupivacaine that may not have been apparent at other times if pain scores were measured at intervals irrespective of the time of drug administration as in our study. We were also unable to demonstrate the benefit noted in the cholecystetomy trials.

It is possible that in this study, a significant amount of bupivacaine was removed by the chest tubes, which did not occur after cholecystectomy. Although the number of patients studied was large enough to detect a difference of 3 on the visual analogue pain scale, there may not have been enough subjects to detect changes in the complication rate or in the use of opiate analgesics. Due to the large standard deviations noted for the use of morphine sulfate, this study would have sulfate. To detect smaller differences in morphine sulfate use would have required a much larger sample size. It is possible that higher doses of bupivacaine may have been effective. However, the dose of bupivacaine used in this study is large compared with most previous trials.[2,3,6,7]

The effects of bupivacaine on preoperative and postoperative pulmonary function tests were not investigated since the alterations in pulmonary function following thoracotomy were most likely to be influenced by volume and location of lung resected.

Thus, although several studies suggest that intrapleural bupivacaine is useful for analgesia following thoracotomy, there are no objective data demonstrating any effectiveness in this prospective, controlled, randomized study. This method of analgesia necessitates the time and expense of placing an additional pleural catheter, injecting the drug, and maintaining the catheter. Unless other randomized, controlled studies verify its usefulness, the administration of intrapleural bupivacaine for postoperative analgesia following thoracotomy is unwarranted.

REFERENCES

[1] Craig D. Postoperative recovery of pulmonary function. Anesth Analg 1981; 60:46-52

[2] Kvalheim, L, Reistad F. Intrapleural catheter in the management of postoperative pain [abstract]. Anesthesiology 1984; 61:A231

[3] Kambam JR, Hammon J, Parris WCV, Lupinetti FM. Intrapleural analgesia for post-thoracotomy pain and blood levels of bupivacaine following intrapleural injection. Can J Anaesth 1989; 36:106-09

[4] McIlvaine WB, Knox RF, Fennessey PV, Goldstein M. Continuous infusion of bupivacaine via intrapleural catheter for analgesia after thoracotomy in children. Anesthesiology 1968; 69: 261-64

[5] McIlvaine WB, Chang JHT, Jones M. The effective use of intrapleural bupivacaine for analgesia after thoracic and subcostal incisions in children. J Pediatr Surg 1988; 23:1184-87

[6] El-Naggar MA, Schaberg FJ Jr, Phillips MR. Intrapleural regional analgesia for pain management in cholecystectomy. Arch Surg 1989; 124:568-70

[7] Seltzer JL, Larijani GE, Goldberg ME, Marr AT. Intrapleural bupivacaine -- a kinetic and dynamic evaluation. Anesthesiology 1987; 67:798-800

[8] Logas WG, El-Baz N, El-Ganzouri A, Cullen M, Staren E, Faber LP, Ivankovich AD. Continuous thoracic epidural analgesia for postoperative pain relief following thoracotomy: a randomized prospective study. Anesthesiology 1987; 67:787-91

[9] El-Baz NM, Faber LP, Jensik R. Continuous epidural infusion of morphine for treatment of pain after thoracic surgery: a new technique. Anesth Analg 1984; 63:757-64

[10] VadeBoncouer TR, Riegler FX, Gautt R, Weinberg L. A randomized, double-blind comparison of the effects of interpleural bupivacaine and saline on morphine requirements and pulmonary function after cholecystectomy. Anesthesiology 1989; 71:339-43

[11] Rosenberg PH, Barbro MAS, Scheinen MA, Lepantalo MA, Lindfors O. Continuous infusion of bupivacaine for analgesia after thoracotomy. Anesthesiology 1987; 67:811-13

[12] Mann LJ, Young GR, Williams JK, Dent OF, McCaughan BC. Intrapleural bupivacaine in the control of postthoracotomy pain. Ann Thorac Surg 1992; 53:449-54

[13] Foley K. The practical use of narcotic analgesics. Med Clin North Am 1982; 66:1091-1104

[14] Symreng T, Gomez MN, Johnson B, Rossi NP. Intrapleural bupivacaine vs saline after thoracotomy: effects on pain and lung function -- a double blind study [abstract]. Anesth Analg 1988; 67:S227

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