Intrapleural Bupivacaine in the Control of Postthoracotomy Pain Lynnette J. Mann, MB, BS, Gretel R. Young, BAppSc(Phty), Jay K. Williams, BAppSc(Phty), Owen F. Dent, PhD, and Brian C. McCaughan, MB, BS, FRACS Departments of Surgery and Physiotherapy, Repatriation General Hospital, Concord, New South Wales, and National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia
A randomized, double-blind trial was conducted to determine the effectiveness of intrapleural bupivacaine hydrochloride in the management of pain after thoracotomy. Thirty-three men and 7 women with a mean age of 62 years (range, 21 to 76 years) undergoing elective posterolateral thoracotomy were randomly allocated preoperatively to either a study group receiving 20 mL of 0.25% bupivacaine or a control group receiving 20 mL of 0.9% saline solution through a pleural catheter every 4 hours. Patients received supplementary doses of intramuscular papaveretum as required. Assessment of pain, somnolence, and breathing capacity was performed after the intrapleural injections at 4, 24, 48, and 72 hours postoperatively. Pain assessment, as measured by a lin-
ear analog scale, was lower in the bupivacaine group at all times, reaching significance at 4,24, and 72 hours ( p < 0.05). The forced vital capacity and forced expiratory volume in 1 second at 6 weeks postoperatively remained significantly lower than preoperatively (p < 0.05). The fall in forced vital capacity from this postoperative level was significantly less in the bupivacaine group at 4, 24, and 48 hours, and the fall in forced expiratory volume in 1 second was significantly less at 4 and 48 hours in the treated group. When used in conjunction with doses of parenteral narcotic, intrapleural bupivacaine gives better pain control with less respiratory depression than intermittent doses of narcotic alone. (Ann Thorac Surg 1992;53:44954)
S
were entered into the study. Written informed consent was obtained from each patient preoperatively. Patients were excluded from entry into the trial if they underwent pneumonectomy or esophagectomy or had any contraindications to the administration of papavereturn or bupivacaine. In all patients, a posterolateral thoracotomy was performed in the fifth intercostal space by or under the supervision of one of us (B.C.M.). Before closure of the thoracotomy, a clear nylon epidural catheter was inserted into the pleural space through a small incision above the thoracotomy using a Tuohy needle and positioned, under direct vision, to lie in the paravertebral gutter. The catheter was sutured to the skin. As is our usual practice, 36F intercostal catheters were placed anteriorly and posteriorly, and the thorax was closed in layers. The two intercostal catheters were connected by an underwaterseal drain to 20 cm H,O suction. Identical vials of 20 mL of 0.25%bupivacaine and 20 mL of 0.9% saline solution, randomized in blocks of four, were supplied by Astra Pharmaceuticals Pty Ltd. Each patient was allocated to one trial solution, identified only by a number, and a sealed copy of the treatment code was made available for emergency use if required. At the conclusion of the operative procedure, 20 mL of “trial solution” was injected into the pleural cavity through the pleural catheter. Every 4 hours, regardless of degree of pain, patients were given further doses of trial solution through the
ince the initial description by Reiestad and Strermskag [l], in 1986 the use of intrapleural anesthetic medication in the control of postoperative pain has become increasingly widespread. The effectiveness of this technique in upper abdominal surgery is well documented [l-61. More controversial is the degree of analgesia provided by this method in patients after a posterolateral thoracotomy [2, 7-11]. At Repatriation General Hospital, Concord, Australia, we commenced using intrapleural injections of 0.25% bupivacaine hydrochloride in patients after posterolateral thoracotomy. The narcotic requirements of 8 patients receiving intrapleural bupivacaine were retrospectively compared with those of 8 patients receiving intramuscular narcotics alone. A 50% reduction in both the total dose and the number of doses of papaveretum over 72 hours was found in the group receiving bupivacaine. On the basis of this observation and in the absence in the literature of adequate randomized, double-blind studies, the following prospective randomized, double-blind trial was undertaken.
Material and Methods With the approval of the hospital ethics committee, 40 patients undergoing elective posterolateral thoracotomy Accepted for publication Aug 23, 1991. Address reprint requests to Dr Mann, Department of Surgery, Clinical Sciences Building, Repatriation General Hospital, Concord, NSW 2139, Australia.
0 1992 by The Society of Thoracic Surgeons
0003-4975/92/$5.00
450
Ann Thorac Surg 1992;53:449-54
MANNETAL INTRAPLEURAL BUPIVACAINE
pleural catheter. The solution was administered by the ward nursing staff with the patient supine and remaining so for 15 minutes after the injection. Drainage of the intercostal catheters was not altered at the time of injection; the suction was not disconnected, nor were the catheters clamped. Supplementary doses of intramuscular papaveretum were given every 4 hours as deemed necessary by the nursing staff to maintain adequate pain relief. The number of doses and the total dose of narcotic were documented. Assessment was performed 20 to 30 minutes after the intrapleural injections at 4, 24, 48, and 72 hours. Patients who had received intramuscular papaveretum less than 2 hours before assessment at 4 hours were excluded from that analysis. At all other assessment times, at least 3 hours had elapsed since the last dose of papaveretum. Patients were asked to assess their current resting pain level using a 10-cm linear analog scale [12] and part 2 of the McGill pain questionnaire [13]. Patients were assigned a rank pain score [3] by the medical officer: 1 = No pain 2 = Pain on deep breathing, coughing, or movement only 3 = Pain present: no narcotic required 4 = Pain present: narcotic required Assessment of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV,), and peak expiratory flow rate (PEFR) was performed by the physical therapist with the patient sitting. The FVC and FEV, were measured using a single Vitalograph bellows spirometer series R in the first 28 patients and a Vitalograph electronicscreen pneumotachograph spirometer (standard program issue 5) in the last 12 patients. The PEFR was measured using a Clement-Clarke miniwright peak flow minimeter. Assessment of pulse rate, blood pressure, respiratory rate, and somnolence was made by the medical officer. Somnolence was ranked on a five-point scale [14]: 1 = Oriented and initiates conversation 2 = Responds to all forms of stimulation and is well oriented, but feels sleepy and does not initiate conversation 3 = Responds to verbal commands and painful stimulation, but is disoriented and does not initiate conversation 4 = Responds to painful stimuli but not to verbal commands 5 = Unresponsive to verbal commands or painful stimuli Removal of the pleural catheter was performed at the time of removal of the intercostal catheters or after 96 hours. Assessment was discontinued at the time of intercostal and pleural catheter removal or after 72 hours. At 6 to 12 weeks postoperatively, the patients were reassessed with respect to pulse rate, blood pressure, respiratory rate, FVC, FEV,, and PEFR.
Table 1 . Patient Characteristics" Variable
Bupivacaine Group
Control Group
15:5
18:2
65.5 41-76 66.3
58.6 21-73 74.8
12 (60) 0 5 (25) 3 (15)
11 (55) 1 (5) 7 (35) 1 (5)
12 (60) 1 (5) 6 (30) 0 1 (5)
9 (45)
Sex (male:female) Age (Y) Mean Range Mean weight (kg)b Diagnosis Non-small cell lung cancer Mesothelioma Benign pathology Secondary malignancy Operation performedb Single lobectomy Two or more lobes resected Wedge resection Open biopsy Pleurodesis f pleurectomy a
Numbers in parentheses are percentages.
0 4 (20) 4 (20) 3 (15)
Significance: p < 0.05.
The data were analyzed by computer using a standard statistical package [15]. The x 2 test was used to assess differences in contingency tables with the significance level set at 0.05. Differences between means were assessed from the relevant 95% confidence intervals (CI). Where patients were excluded from analysis, either because narcotics had been administered within the preceding 2 hours (4-hour assessment) or because the intercostal catheters had been removed, the total group size for analysis was taken as the remaining number of patients.
Results There were 33 men and 7 women with a mean age of 62 years (range, 21 to 76 years). Table 1 lists the patient characteristics. Despite randomization, the bupivacaine group had a significantly lower mean weight than the control group. Significantly more patients in the bupivacaine group had a wedge or more of lung resected than in the control group. At 4 hours postoperatively, 33 patients completed the linear analog scale; 29, the McGill questionnaire; and 36, respiratory function tests. Excluding those who had received papaveretum in the preceding 2 hours, results were available for 27 patients on the linear analog scale, for 24 on the McGill questionnaire, and for 30 on assessment of respiratory function. One patient in the control group was still too drowsy to complete the McGill questionnaire at 24 hours, but all other patients completed the full assessment. Four patients had the intercostal and pleural catheters removed before the 48-hour assessment, and another 10 had the catheters removed before the 72-hour assessment. Figure 1 shows the mean pain scores measured by the linear analog scale. The bupivacaine group had lower
MANNETAL INTRAPLEURAL BUPIVACAINE
Ann Thorac Surg 1992;53:44%54
scores at all times, reaching significance at 4 hours, 24 hours, and 72 hours. The bupivacaine group also had significantly lower rank pain scores at 4 hours and 72 hours (Fig 2). Two methods were used to calculate a pain score from the McGill questionnaire. The mean number of words chosen by the patient showed no significant differences between the two groups. However, the mean score of the words (ranked according to each word's position within its group) chosen by the experimental group was less than or equal to the control group at all times and significantly lower at 4 hours postoperatively (experimental group mean = 11.5, 95%CI = 4.8 to 18.2; control group mean = 20.5, 95% CI = 13.8 to 27.1). There was no significant difference between the groups at any time in the absolute values of FVC, FEV,, or PEFR or in the fall of these values from the preoperative levels. In the 31 patients whose respiratory function was assessed at 6 weeks postoperatively, all values remained significantly lower at that time compared with preoperative levels (Fig 3). These 6-week values were taken as the baseline, and all changes in breathing capacity were calculated from this level. The bupivacaine group had a significantly smaller fall in FVC at 4 hours, 24 hours, and 48 hours (Fig 4). The bupivacaine group had a smaller fall in FEV, at all times (Fig 5), reaching significance at 4 hours and 48 hours. There was no significant difference in the fall in PEFR between the two groups at any time. There was no difference in the somnolence scores of the two groups at any t'me. Likewise, there was no difference in pulse rate, respiratory rate, or diastolic blood pressure. There was a significant difference in mean systolic blood pressure at 4 hours (bupivacaine group mean = 123 mm Hg, 95%CI = 114 to 132; control group mean = 139 mm Hg, 95% CI = 129 to 149). The mean number of doses of papaveretum was the same for both groups. However, the mean total dose administered was significantly less in the bupivacaine group at 24 hours (bupivacaine group mean = 48.8 mg, 95%CI = 37.5 to 60.1; control group mean = 65.3 mg, 95%
Mean Score (mm) +I- 95% ci
QO1
100 80
en 701
A randomized, double-blind trial was conducted to determine the effectiveness of intrapleural bupivacaine hydrochloride in the management of pain after thoracotomy. Thirty-three men and 7 women with a mean age of 62 years (range, 21 to 76 years) undergoing elective posterolateral thoracotomy were randomly allocated preoperatively to either a study group receiving 20 mL of 0.25% bupivacaine or a control group receiving 20 mL of 0.9% saline solution through a pleural catheter every 4 hours. Patients received supplementary doses of intramuscular papaveretum as required. Assessment of pain, somnolence, and breathing capacity was performed after the intrapleural injections at 4, 24, 48, and 72 hours postoperatively. Pain assessment, as measured by a lin-
ear analog scale, was lower in the bupivacaine group at all times, reaching significance at 4,24, and 72 hours ( p < 0.05). The forced vital capacity and forced expiratory volume in 1 second at 6 weeks postoperatively remained significantly lower than preoperatively (p < 0.05). The fall in forced vital capacity from this postoperative level was significantly less in the bupivacaine group at 4, 24, and 48 hours, and the fall in forced expiratory volume in 1 second was significantly less at 4 and 48 hours in the treated group. When used in conjunction with doses of parenteral narcotic, intrapleural bupivacaine gives better pain control with less respiratory depression than intermittent doses of narcotic alone. (Ann Thorac Surg 1992;53:44954)
S
were entered into the study. Written informed consent was obtained from each patient preoperatively. Patients were excluded from entry into the trial if they underwent pneumonectomy or esophagectomy or had any contraindications to the administration of papavereturn or bupivacaine. In all patients, a posterolateral thoracotomy was performed in the fifth intercostal space by or under the supervision of one of us (B.C.M.). Before closure of the thoracotomy, a clear nylon epidural catheter was inserted into the pleural space through a small incision above the thoracotomy using a Tuohy needle and positioned, under direct vision, to lie in the paravertebral gutter. The catheter was sutured to the skin. As is our usual practice, 36F intercostal catheters were placed anteriorly and posteriorly, and the thorax was closed in layers. The two intercostal catheters were connected by an underwaterseal drain to 20 cm H,O suction. Identical vials of 20 mL of 0.25%bupivacaine and 20 mL of 0.9% saline solution, randomized in blocks of four, were supplied by Astra Pharmaceuticals Pty Ltd. Each patient was allocated to one trial solution, identified only by a number, and a sealed copy of the treatment code was made available for emergency use if required. At the conclusion of the operative procedure, 20 mL of “trial solution” was injected into the pleural cavity through the pleural catheter. Every 4 hours, regardless of degree of pain, patients were given further doses of trial solution through the
ince the initial description by Reiestad and Strermskag [l], in 1986 the use of intrapleural anesthetic medication in the control of postoperative pain has become increasingly widespread. The effectiveness of this technique in upper abdominal surgery is well documented [l-61. More controversial is the degree of analgesia provided by this method in patients after a posterolateral thoracotomy [2, 7-11]. At Repatriation General Hospital, Concord, Australia, we commenced using intrapleural injections of 0.25% bupivacaine hydrochloride in patients after posterolateral thoracotomy. The narcotic requirements of 8 patients receiving intrapleural bupivacaine were retrospectively compared with those of 8 patients receiving intramuscular narcotics alone. A 50% reduction in both the total dose and the number of doses of papaveretum over 72 hours was found in the group receiving bupivacaine. On the basis of this observation and in the absence in the literature of adequate randomized, double-blind studies, the following prospective randomized, double-blind trial was undertaken.
Material and Methods With the approval of the hospital ethics committee, 40 patients undergoing elective posterolateral thoracotomy Accepted for publication Aug 23, 1991. Address reprint requests to Dr Mann, Department of Surgery, Clinical Sciences Building, Repatriation General Hospital, Concord, NSW 2139, Australia.
0 1992 by The Society of Thoracic Surgeons
0003-4975/92/$5.00
450
Ann Thorac Surg 1992;53:449-54
MANNETAL INTRAPLEURAL BUPIVACAINE
pleural catheter. The solution was administered by the ward nursing staff with the patient supine and remaining so for 15 minutes after the injection. Drainage of the intercostal catheters was not altered at the time of injection; the suction was not disconnected, nor were the catheters clamped. Supplementary doses of intramuscular papaveretum were given every 4 hours as deemed necessary by the nursing staff to maintain adequate pain relief. The number of doses and the total dose of narcotic were documented. Assessment was performed 20 to 30 minutes after the intrapleural injections at 4, 24, 48, and 72 hours. Patients who had received intramuscular papaveretum less than 2 hours before assessment at 4 hours were excluded from that analysis. At all other assessment times, at least 3 hours had elapsed since the last dose of papaveretum. Patients were asked to assess their current resting pain level using a 10-cm linear analog scale [12] and part 2 of the McGill pain questionnaire [13]. Patients were assigned a rank pain score [3] by the medical officer: 1 = No pain 2 = Pain on deep breathing, coughing, or movement only 3 = Pain present: no narcotic required 4 = Pain present: narcotic required Assessment of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV,), and peak expiratory flow rate (PEFR) was performed by the physical therapist with the patient sitting. The FVC and FEV, were measured using a single Vitalograph bellows spirometer series R in the first 28 patients and a Vitalograph electronicscreen pneumotachograph spirometer (standard program issue 5) in the last 12 patients. The PEFR was measured using a Clement-Clarke miniwright peak flow minimeter. Assessment of pulse rate, blood pressure, respiratory rate, and somnolence was made by the medical officer. Somnolence was ranked on a five-point scale [14]: 1 = Oriented and initiates conversation 2 = Responds to all forms of stimulation and is well oriented, but feels sleepy and does not initiate conversation 3 = Responds to verbal commands and painful stimulation, but is disoriented and does not initiate conversation 4 = Responds to painful stimuli but not to verbal commands 5 = Unresponsive to verbal commands or painful stimuli Removal of the pleural catheter was performed at the time of removal of the intercostal catheters or after 96 hours. Assessment was discontinued at the time of intercostal and pleural catheter removal or after 72 hours. At 6 to 12 weeks postoperatively, the patients were reassessed with respect to pulse rate, blood pressure, respiratory rate, FVC, FEV,, and PEFR.
Table 1 . Patient Characteristics" Variable
Bupivacaine Group
Control Group
15:5
18:2
65.5 41-76 66.3
58.6 21-73 74.8
12 (60) 0 5 (25) 3 (15)
11 (55) 1 (5) 7 (35) 1 (5)
12 (60) 1 (5) 6 (30) 0 1 (5)
9 (45)
Sex (male:female) Age (Y) Mean Range Mean weight (kg)b Diagnosis Non-small cell lung cancer Mesothelioma Benign pathology Secondary malignancy Operation performedb Single lobectomy Two or more lobes resected Wedge resection Open biopsy Pleurodesis f pleurectomy a
Numbers in parentheses are percentages.
0 4 (20) 4 (20) 3 (15)
Significance: p < 0.05.
The data were analyzed by computer using a standard statistical package [15]. The x 2 test was used to assess differences in contingency tables with the significance level set at 0.05. Differences between means were assessed from the relevant 95% confidence intervals (CI). Where patients were excluded from analysis, either because narcotics had been administered within the preceding 2 hours (4-hour assessment) or because the intercostal catheters had been removed, the total group size for analysis was taken as the remaining number of patients.
Results There were 33 men and 7 women with a mean age of 62 years (range, 21 to 76 years). Table 1 lists the patient characteristics. Despite randomization, the bupivacaine group had a significantly lower mean weight than the control group. Significantly more patients in the bupivacaine group had a wedge or more of lung resected than in the control group. At 4 hours postoperatively, 33 patients completed the linear analog scale; 29, the McGill questionnaire; and 36, respiratory function tests. Excluding those who had received papaveretum in the preceding 2 hours, results were available for 27 patients on the linear analog scale, for 24 on the McGill questionnaire, and for 30 on assessment of respiratory function. One patient in the control group was still too drowsy to complete the McGill questionnaire at 24 hours, but all other patients completed the full assessment. Four patients had the intercostal and pleural catheters removed before the 48-hour assessment, and another 10 had the catheters removed before the 72-hour assessment. Figure 1 shows the mean pain scores measured by the linear analog scale. The bupivacaine group had lower
MANNETAL INTRAPLEURAL BUPIVACAINE
Ann Thorac Surg 1992;53:44%54
scores at all times, reaching significance at 4 hours, 24 hours, and 72 hours. The bupivacaine group also had significantly lower rank pain scores at 4 hours and 72 hours (Fig 2). Two methods were used to calculate a pain score from the McGill questionnaire. The mean number of words chosen by the patient showed no significant differences between the two groups. However, the mean score of the words (ranked according to each word's position within its group) chosen by the experimental group was less than or equal to the control group at all times and significantly lower at 4 hours postoperatively (experimental group mean = 11.5, 95%CI = 4.8 to 18.2; control group mean = 20.5, 95% CI = 13.8 to 27.1). There was no significant difference between the groups at any time in the absolute values of FVC, FEV,, or PEFR or in the fall of these values from the preoperative levels. In the 31 patients whose respiratory function was assessed at 6 weeks postoperatively, all values remained significantly lower at that time compared with preoperative levels (Fig 3). These 6-week values were taken as the baseline, and all changes in breathing capacity were calculated from this level. The bupivacaine group had a significantly smaller fall in FVC at 4 hours, 24 hours, and 48 hours (Fig 4). The bupivacaine group had a smaller fall in FEV, at all times (Fig 5), reaching significance at 4 hours and 48 hours. There was no significant difference in the fall in PEFR between the two groups at any time. There was no difference in the somnolence scores of the two groups at any t'me. Likewise, there was no difference in pulse rate, respiratory rate, or diastolic blood pressure. There was a significant difference in mean systolic blood pressure at 4 hours (bupivacaine group mean = 123 mm Hg, 95%CI = 114 to 132; control group mean = 139 mm Hg, 95% CI = 129 to 149). The mean number of doses of papaveretum was the same for both groups. However, the mean total dose administered was significantly less in the bupivacaine group at 24 hours (bupivacaine group mean = 48.8 mg, 95%CI = 37.5 to 60.1; control group mean = 65.3 mg, 95%
Mean Score (mm) +I- 95% ci
QO1
100 80
en 701
