- Email: [email protected]
Interpleural analgesia with bupivacaine following thoracotomy: Ineffective results of a controlled study and pharmacokinetics
Interpleural Analgesia with Bupivacaine following Thoracotomy: Ineffective Results of a-Controlled Study and Pharmacokinetics Annie Elman, MD,* Bertrand Debaene, MD,* Chantal Magny-Metrot, MD,? Guy Murciano, MD$ Departments France.
*Assistant Professor of Anesthesiology tStaff Anesthesiologist $Assistant Professor of Vascular Surgery Address reprint requests to Dr. Elman at the Department of Anesthesiology, Hopital Beaujon, 92100 Clichy, France. Supported by a grant from Roger Bellon,
of Anesthesiology and Vascular Surgery, Hopital Beaujon, Clichy,
Study Objective: To evaluate intrapleural analgesia with bupivacaine jollowingpartial pulmonary resection and to determine pharmacokinetic parameters of bupivacaine with epinephrine. Design: Prospective, randomized study. Setting: Thoracic surgical clinic of a university-affiliated general hospital. Patients: Eighteen consecutive patients (13 men, 5 women) scheduled for pulmonary surgery by posterolateral thoracotomy. Interventions: Bupivacaine was administered through an intrapleural catheter as o bolus dose of either 40 ml of 0.25% bupivacaine with epinephrine (0.5 mg per 100 ml of solution) (n = 10) or 20 ml of 0.5% bupivacaine with epinephrine (0.5 mg per 100 ml of solution) (n = 8) up to three times daily for a maximum time of 4 days. Measurements and Main Results: Subjective evaluation of pain was performed using the visual analog scale (VAS) before and after each injection by response to spontaneous pain, coughing, deep breathing, and incision palpation. Maximum peak concentration (C Max) and maximum time to reach the peak concentration (T Max) were assessed after the first and last injections. Although VAS pain score decreased signaficantly, pain relief was not sufficient. C Max and T Max after the first and last injections were not signzficantly dafferent between the two groups. In each group, C Max after the last injection was significantly higher than after the first injection, Conclusions: Intrapleural analgesia conducted with 40 ml of 0.25% bupivacaine with epinephrine or 20 ml of 0.5% bup ivacaine with epinephrine was insufficient for pain, despite high plasma bupivacaine concentration.
Inc., Neuilly, France. Presented at the Annual Meeting of the American Society of Anesthesiologists, Las Vegas, October 19-23, 1990. Received for publication December 4, 1991; revised manuscript accepted for publication October 23, 1992. 0 1993 Butter-worth-Heinemann J. Clin. Anesth. 5:118-121, 1993.
118
J. Clin. Anesth.,
vol. 5, March/April
Keywords: Analgesia, postoperative; anesthetics, local; bupivacaine; anesthetic technique, interpleural; pain, postoperative.
Introduction A new postoperative analgesia technique, intrapleural analgesia, has recently become popular. 1,2 However, its efficacy in relieving pain following thoracotomy is a much-debated question.“-5 This could be related to the fact that 1993
Interpleural
the patients in previous studies were undergoing various surgical procedures-anterior and lateral or posterior and lateral thoracotomy, pneumonectomy, partial resection of the lung, or nonpulmonary surgery-and were receiving other medications, such as opioids, for postoperative pain relief. Moreover, until recently, no controlled study had been conducted in the field, and the appropriate volumes and concentrations of solutions to provide a long duration of analgesia following thoracotomy had not been investigated. Therefore, this prospective, controlled study was undertaken to assess whether intrapleural anesthesia is effective in providing pain relief after thoracotomy for lung surgery and to study the pharmacokinetics of bupivacaine with epinephrine.
Materials and Methods Eighteen consecutive patients (13 men, 5 women) were included in the study after we obtained informed consent and approval of the Hopital Beaujon Local Ethical Committee. Patient exclusion criteria were anterior thoracotomy, total pneumonectomy, pleural abrasion, pleural or pulmonary biopsy, pleural infection and effusion, mechanical ventilation more than 4 hours postoperatively, intraventricular conduction defects, and seizure. Premeditation consisted of atropine and hydroxyzine 1.5 mg/kg intramuscularly 90 minutes before surgery. Anesthesia was induced with thiopental sodium 5 mgl kg, fentany13 *g/kg, and pancuronium bromide 0.1 mgl kg; it was maintained with repeated injections of fentanyl 1 p,g/kg and isoflurane 1 minimum alveolar concentration in oxygen. All patients were intubated using a selective endobronchial tube and ventilated with a Siemens ventilator (Siemens, Solna, Sweden). The surgical procedure, which consisted of a lobectomy or wedge resection, was performed through a posterolateral thoracotomy. Following lung resection, patients were included in the study. Before chest closure, the surgeon inserted an epidural catheter posteriorly into the pleural space through the intercostal space adjacent to the incision site, according to the technique described by Kambam et ~1.~Then the patient was randomly assigned to one of two groups. The first group (n = 10) received 0.25% bupivacaine with epinephrine 1:200,000 in a 40 ml solution. The second group (n = 8) received 0.5% bupivacaine with epinephrine in a 20 ml solution. Each patient in both groups received a total dose of 100 mg of bupivacaine in each injection. Concentrations and volumes of the solutions were different in each group. The first injection was given as soon as the patient was alert, 1 to 2 hours following the surgical procedure. Subsequent doses were given up to three times a day for a maximum duration of 4 days. During and after injection, the patients were maintained in a semirecumbent position. The chest catheter was clamped for 10 minutes following injection. On request, patients could receive other analgesic medications (i.e., either paracetamol and dextropropoxyphene or salicy-
analgesia with bupiuacaine
after thoracotomy:
Elman
et al.
lates) except morphine. Subjective evaluation of pain was determined using a 0 to 10 visual analog scale (VAS) just before and 30 minutes after each injection for the following criteria: spontaneous pain, deep breathing, coughing, palpation of the incision site. Simultaneously, heart rate (HR), mean arterial pressure (MAP), respiratory rate, and forced vital capacity (FVC) were recorded. Blood gases were measured daily. Following the first and last injections, maximum peak concentration (C Max) of bupivacaine and maximum time to reach the peak (T Max) were estimat.ed. Venous samples were withdrawn at 0, 5, 10, 15,20,30, and 40 minutes after the first injection and 10,20,30, and 40 minutes after the last injection. The samples were immediately centrifuged at 4,000 rpm for 10 minutes. The serum was decanted and stored at - 18°C until the time of analysis. Bupivacaine plasma concentration was measured using a model 3400 Varian gas chromatograph (Varian France, Les Ulis, France) with a nitrogen specific detector. Etidocaine was used as the internal standard, and a single extraction in toluene was performed. The limit of detection of bupivacaine was 0.01 p.g/ml. The coefficient of variation was less than 12% at 0.03 kg/ml and less than 5% at 0.2 pg/ml. Statistical analysis of clinical data and pharmacologic parameters were calculated using the Mann-Whitney U test and the Wilcoxon test. A value of p < 0.05 was considered significant. Results are expressed as means 2 SD.
Results Eighteen patients from 32 to 73 years of age received a total of 97 injections for a maximum time of 4 days. The two groups were comparable in height, weight, number of injections, and preoperative values for ventilatory function and hemodynamic function (Table 1). Patients in Group 1 were significantly younger than patients in Group 2 (p < 0.03). Although the VAS pain score decreased significantly after injection in both groups (p < O.OOl), the level remained high: 4 by spontaneous pain on the VAS and 5 following deep breathing, coughing, and palpation of Table 1. Clinical Data in the Two Patient Groups Group
Patients (n) Injections (n) Age (yr) Weight (kg) Height (cm) FEV, (I) MAP (mmHg) HR @pm)
50 68 165 1.9 95 80
10 53 + t + 2 + +
1
Group
2
13 15 9 8.9 9 7
8 44 k + + r + +
7* 9 8 1.5 8 5
61 67 164 1.8 94 78
*Significantly different from Group 1; p < 0.03. Note: Data are means f SD. FEV, = forced expiratory volume in 1 second; MAP = mean arterial pressure; HR = heart rate; bpm = beats per minute.
J. Clin. Anesth.,
vol. 5, March/April
1993
119
Original Contributions
Figure 1. Visual analog scale (VAS) pain score before and after injection * significantly different from values obtained before injection; p < 0.01.
the incision site (Figure 1). Pain relief was inadequate according to Dodson’s standards.6 The pain score before any injection was higher in Group 1 than in Group 2. The difference sustained after injections and during the follow-up, and the percentage of variation was the same in both groups (Figure I). There was no change in blood gases between the two groups, although a small but significant increase was recorded in FVC following injection: 627 + 31 ml versus 709 2 35 ml in Group 1; 705 + 47 ml ver~w 772 + 48 ml in Group 2 (p < 0.05). No variation in HR and no effect on MAP were recorded following pleural injection in either group. However, in Group 1, MAP was higher before injection compared with Group 2, and this difference was sustained after injection and during the follow-up (Table 2). Pharmacokinetic parameters are shown in Table 3. In the two groups, C Max increased significantly from the first to the last injection, suggesting a cumulative effect. The increase in T Max between the first and the last injection was not significant in either group. C Max and T Max also did not differ between the groups. No morphine was given to the patients. Ten patients received dextropropoxyphene and paracetamol and one received salicylates as analgesic medication. The patients receiving these drugs were equally allocated to each group. Discussion Despite the statistically significant increase in FVC and the decrease in the VAS pain score following interpleural injection of bupivacaine and epinephrine in thoracotomy patients, our study showed that intrapleural analgesia was inefficient. The VAS score following intrapleural analgesia decreased only to 4 or 5, which is the severity of pain usually required to include patients in clinical analgesia trials.7 Thus, pain relief was too poor to demonstrate the effectiveness of this technique. Only posterolateral thoracotomies were included in this study, since previous studies have shown that ante120
J. Clin. Anesth.,
vol. 5, March/April
1993
of bupivacaine
in both
groups
(means
it SD).
Table 2. Heart Rate (HR) and Mean Arterial Pressure (MAP) Variations following Injections in Groups 1 and 2 Group 1 HR &pm) Before After MAP (mmHg) Before After *Significantly different
Group 2
97 2 13 97 f 13
91 t 24 91 ? 24
104 * 12 101 f 12
94 -r- 12* 93 r to*
from Group 1; p < 0.01.
Note: Data are means 2 SD. Before = before injection; after = following injection.
Table 3. Pharmacokinetic Parameters of Bupivacaine 100 mg after the First and Last Injections in Both Groups Group 1
Group 2
0.75 Y?0.57 2.11 * 0.71*
0.42 + 0.29 1.53 t 0.60*
25 + 11 39 + 9
23 ? 14 33 t 8
C Max (kg/ml)
First injection Last injection T Max (min) First injection Last injection
*Significantly higher than after the first injection; p < 0.01. Note: Data are means t SD. C Max = maximum peak concentration; T Max = maximum time to reach peak concentration. rior thoracotomy pain is not relieved with intrapleural analgesia.4 Intrapleural bupivacaine produces an intercostal nerve block, and distribution of local anesthetic solution is determined by gravity in the dependent area of the pleural space.* To maintain the intrapleural distribution of bupivacaine, we did not include patients with total pneumonectomy in the study, and to favor a paravertebral block, we gave injections to patients in the semi-
Interpleural
recumbent position .g Loss of drug via chest tubes was prevented by clamping for 10 minutes following injection.s,6 We used bupivacaine with epinephrine to lower the maximum peak concentration.4 We selected a total dose of bupivacaine 100 mg for each injection based on the initial reports of interpleural analgesia for cholecystectomy: Seltzer et al.10 obtained a high plasma maximum peak concentration (2.07 kg/ml) with a dose of 150 mg, and Stramskag et al. I1 found a lower plasma concentration (1.20 pg/ml) with a dose of 100 mg. Groups 1 and 2 were comparable in height and weight. To administer the same total dose at each injection to both groups, we used 0.5% and 0.25% bupivacaine. No difference was observed in percentage of pain variation between the groups, suggesting that concentration does not influence pain relief when the volume is different. Although intrapleural injection of bupivacaine decreased the VAS score, the efficacy of this technique remains questionable. The score was still too high for the injection to be considered effective6 and was comparable to that in other studies where opioids were used with intrapleural bupivacaine.3,7 The difference in pain score before injection between the two groups was probably related to the difference in patient ages. As with the pain score, FVC improved, but the mean increase was only 82 -+ 14 ml in Group 1 and 67 2 17 ml in Group 2. This seemed very low compared with the large increase in FVC obtained after intrapleural analgesia for cholecystectomy.12,13 To compare the plasma concentration between the first and the last injection, we measured bupivacaine on venous blood samples, since the arterial catheter in these patients is usually removed 24 hours postoperatively. Thus, the plasma concentration was lower than in studies using arterial blood samples.14 In our study, clamping of the chest tube was long enough to keep most of the drug effective. In fact, our plasma concentration was comparable to the venous concentration found after cholecystectomy in which no drug was lost.12 Following the first injection, the plasma concentration was similar in both groups. With equal doses and different concentrations and volumes, there was no change in C Max between the two groups, although C Max did increase from the first to the last injection. This cumulative effect precluded the use of higher bupivacaine doses. In summary, intrapleural analgesia with bupivacaine in a 10 ml or 20 ml solution and epinephrine was inef-
analgesia
with bupivacaine
after thoracotomy:
Elman
et al.
fective in relieving pain following thoracotomy for lung resection. However, with repeated pleural injections for a maximum time of 4 days, a cumulative effect was obtained, preventing us from testing higher doses.
References I. Reiestad F, Strijmskag KE: Interpleural catheter in the management of postoperative pain. A preliminary report. Reg An&h 1986;11:89-91. 2. McIlvaine WB, Knox RF, Fennessey PV, Goldstein M: Continuous infusion of bupivacaine via intrapleural catheter for analgesia after thoracotomy in children. Anesthesiology 1988;69:261-4. 3. Rosenberg PH, Scheinin BM, LepPntalo MJ, Lindors 0: Continuous intrapleural infusion of bupivacaine for analgesia after thoracotomy. Anesthesiology 1987;67:81 l-3. 4. Kambam JR, Hammon J, Parris WC, Lupinetti FM: Intrapleural analgesia for postthoracotomy pain and blood levels of bupivacaine following intrapleural injection. Can J Anaesth 1989;36: 106-9. 5. Covino BG: Interpleural regional analgesia. Anesth Analg 1988;67:427-9. 6. Dodson ME: The methodology of studies of postoperative pain and analgesia. In: Feldman SA, Scurr CF, eds. Current Topics in Anaesthesia Serzes. Vol. 8: The Management of Postoperative Pain. London: Edward Arnold, 1985:31-49. 7. Ferrante FM, Chan VW, Arthur GR, Rocco AG: Interpleural analgesia after thoracotomy. Anesth Analg 1991;72:105-9. 8. Riegler FX, VadeBoncouer TR, Pelligrino DA: Interpleural anesthetics in the dog: differential somatic neural blockade. Anesthesioloa 1989;71:744-50. 9. Strijmskag KE, Hauge 0, Steen PA: Distribution of local anaesthetics injected into the interpleural space, studied by computerized tomography. Acta Anaesthesiol &and 1990;34:323-6. 10. Seltzer JL, Larijani GE, Goldberg ME, Marr AT: Intrapleural bupivacaine-a kinetic and dynamic evaluation. Anesthesiology 1987;67:798-800. 11. Striimskag KE, Reiestad F, Holmqvist EL, Ogenstad S: Intrapleural administration of 0.25%, 0.375%, and 0.5% bupivaCaine with epinephrine after cholecystectomy. Anesth Analg 1988;67:430-4. 12. Brismar B, Pettersson N, Tokics L, Strandberg A, Hedenstierna G: Postoperative analgesia with intrapleural administration of bupivacaine-adrenaline. Acta Anaesthesiol &and 1987;31:515-20. 13. Frenette L, Boudreault D, Guay J: Interpleural analgesia improves pulmonary function after cholecystectomy. Can J Anaesth 1991;38:71-4. PO, et al: Arterial and 14. Moore DC, Mather LE, Bridenbaugh venous plasma levels of bupivacaine following epidural and intercostal nerve blocks. Anesthesiology 1976;45:39-45.
J. Clin.
Anesth.,
vol. 5, March/April
1993
121
*Assistant Professor of Anesthesiology tStaff Anesthesiologist $Assistant Professor of Vascular Surgery Address reprint requests to Dr. Elman at the Department of Anesthesiology, Hopital Beaujon, 92100 Clichy, France. Supported by a grant from Roger Bellon,
of Anesthesiology and Vascular Surgery, Hopital Beaujon, Clichy,
Study Objective: To evaluate intrapleural analgesia with bupivacaine jollowingpartial pulmonary resection and to determine pharmacokinetic parameters of bupivacaine with epinephrine. Design: Prospective, randomized study. Setting: Thoracic surgical clinic of a university-affiliated general hospital. Patients: Eighteen consecutive patients (13 men, 5 women) scheduled for pulmonary surgery by posterolateral thoracotomy. Interventions: Bupivacaine was administered through an intrapleural catheter as o bolus dose of either 40 ml of 0.25% bupivacaine with epinephrine (0.5 mg per 100 ml of solution) (n = 10) or 20 ml of 0.5% bupivacaine with epinephrine (0.5 mg per 100 ml of solution) (n = 8) up to three times daily for a maximum time of 4 days. Measurements and Main Results: Subjective evaluation of pain was performed using the visual analog scale (VAS) before and after each injection by response to spontaneous pain, coughing, deep breathing, and incision palpation. Maximum peak concentration (C Max) and maximum time to reach the peak concentration (T Max) were assessed after the first and last injections. Although VAS pain score decreased signaficantly, pain relief was not sufficient. C Max and T Max after the first and last injections were not signzficantly dafferent between the two groups. In each group, C Max after the last injection was significantly higher than after the first injection, Conclusions: Intrapleural analgesia conducted with 40 ml of 0.25% bupivacaine with epinephrine or 20 ml of 0.5% bup ivacaine with epinephrine was insufficient for pain, despite high plasma bupivacaine concentration.
Inc., Neuilly, France. Presented at the Annual Meeting of the American Society of Anesthesiologists, Las Vegas, October 19-23, 1990. Received for publication December 4, 1991; revised manuscript accepted for publication October 23, 1992. 0 1993 Butter-worth-Heinemann J. Clin. Anesth. 5:118-121, 1993.
118
J. Clin. Anesth.,
vol. 5, March/April
Keywords: Analgesia, postoperative; anesthetics, local; bupivacaine; anesthetic technique, interpleural; pain, postoperative.
Introduction A new postoperative analgesia technique, intrapleural analgesia, has recently become popular. 1,2 However, its efficacy in relieving pain following thoracotomy is a much-debated question.“-5 This could be related to the fact that 1993
Interpleural
the patients in previous studies were undergoing various surgical procedures-anterior and lateral or posterior and lateral thoracotomy, pneumonectomy, partial resection of the lung, or nonpulmonary surgery-and were receiving other medications, such as opioids, for postoperative pain relief. Moreover, until recently, no controlled study had been conducted in the field, and the appropriate volumes and concentrations of solutions to provide a long duration of analgesia following thoracotomy had not been investigated. Therefore, this prospective, controlled study was undertaken to assess whether intrapleural anesthesia is effective in providing pain relief after thoracotomy for lung surgery and to study the pharmacokinetics of bupivacaine with epinephrine.
Materials and Methods Eighteen consecutive patients (13 men, 5 women) were included in the study after we obtained informed consent and approval of the Hopital Beaujon Local Ethical Committee. Patient exclusion criteria were anterior thoracotomy, total pneumonectomy, pleural abrasion, pleural or pulmonary biopsy, pleural infection and effusion, mechanical ventilation more than 4 hours postoperatively, intraventricular conduction defects, and seizure. Premeditation consisted of atropine and hydroxyzine 1.5 mg/kg intramuscularly 90 minutes before surgery. Anesthesia was induced with thiopental sodium 5 mgl kg, fentany13 *g/kg, and pancuronium bromide 0.1 mgl kg; it was maintained with repeated injections of fentanyl 1 p,g/kg and isoflurane 1 minimum alveolar concentration in oxygen. All patients were intubated using a selective endobronchial tube and ventilated with a Siemens ventilator (Siemens, Solna, Sweden). The surgical procedure, which consisted of a lobectomy or wedge resection, was performed through a posterolateral thoracotomy. Following lung resection, patients were included in the study. Before chest closure, the surgeon inserted an epidural catheter posteriorly into the pleural space through the intercostal space adjacent to the incision site, according to the technique described by Kambam et ~1.~Then the patient was randomly assigned to one of two groups. The first group (n = 10) received 0.25% bupivacaine with epinephrine 1:200,000 in a 40 ml solution. The second group (n = 8) received 0.5% bupivacaine with epinephrine in a 20 ml solution. Each patient in both groups received a total dose of 100 mg of bupivacaine in each injection. Concentrations and volumes of the solutions were different in each group. The first injection was given as soon as the patient was alert, 1 to 2 hours following the surgical procedure. Subsequent doses were given up to three times a day for a maximum duration of 4 days. During and after injection, the patients were maintained in a semirecumbent position. The chest catheter was clamped for 10 minutes following injection. On request, patients could receive other analgesic medications (i.e., either paracetamol and dextropropoxyphene or salicy-
analgesia with bupiuacaine
after thoracotomy:
Elman
et al.
lates) except morphine. Subjective evaluation of pain was determined using a 0 to 10 visual analog scale (VAS) just before and 30 minutes after each injection for the following criteria: spontaneous pain, deep breathing, coughing, palpation of the incision site. Simultaneously, heart rate (HR), mean arterial pressure (MAP), respiratory rate, and forced vital capacity (FVC) were recorded. Blood gases were measured daily. Following the first and last injections, maximum peak concentration (C Max) of bupivacaine and maximum time to reach the peak (T Max) were estimat.ed. Venous samples were withdrawn at 0, 5, 10, 15,20,30, and 40 minutes after the first injection and 10,20,30, and 40 minutes after the last injection. The samples were immediately centrifuged at 4,000 rpm for 10 minutes. The serum was decanted and stored at - 18°C until the time of analysis. Bupivacaine plasma concentration was measured using a model 3400 Varian gas chromatograph (Varian France, Les Ulis, France) with a nitrogen specific detector. Etidocaine was used as the internal standard, and a single extraction in toluene was performed. The limit of detection of bupivacaine was 0.01 p.g/ml. The coefficient of variation was less than 12% at 0.03 kg/ml and less than 5% at 0.2 pg/ml. Statistical analysis of clinical data and pharmacologic parameters were calculated using the Mann-Whitney U test and the Wilcoxon test. A value of p < 0.05 was considered significant. Results are expressed as means 2 SD.
Results Eighteen patients from 32 to 73 years of age received a total of 97 injections for a maximum time of 4 days. The two groups were comparable in height, weight, number of injections, and preoperative values for ventilatory function and hemodynamic function (Table 1). Patients in Group 1 were significantly younger than patients in Group 2 (p < 0.03). Although the VAS pain score decreased significantly after injection in both groups (p < O.OOl), the level remained high: 4 by spontaneous pain on the VAS and 5 following deep breathing, coughing, and palpation of Table 1. Clinical Data in the Two Patient Groups Group
Patients (n) Injections (n) Age (yr) Weight (kg) Height (cm) FEV, (I) MAP (mmHg) HR @pm)
50 68 165 1.9 95 80
10 53 + t + 2 + +
1
Group
2
13 15 9 8.9 9 7
8 44 k + + r + +
7* 9 8 1.5 8 5
61 67 164 1.8 94 78
*Significantly different from Group 1; p < 0.03. Note: Data are means f SD. FEV, = forced expiratory volume in 1 second; MAP = mean arterial pressure; HR = heart rate; bpm = beats per minute.
J. Clin. Anesth.,
vol. 5, March/April
1993
119
Original Contributions
Figure 1. Visual analog scale (VAS) pain score before and after injection * significantly different from values obtained before injection; p < 0.01.
the incision site (Figure 1). Pain relief was inadequate according to Dodson’s standards.6 The pain score before any injection was higher in Group 1 than in Group 2. The difference sustained after injections and during the follow-up, and the percentage of variation was the same in both groups (Figure I). There was no change in blood gases between the two groups, although a small but significant increase was recorded in FVC following injection: 627 + 31 ml versus 709 2 35 ml in Group 1; 705 + 47 ml ver~w 772 + 48 ml in Group 2 (p < 0.05). No variation in HR and no effect on MAP were recorded following pleural injection in either group. However, in Group 1, MAP was higher before injection compared with Group 2, and this difference was sustained after injection and during the follow-up (Table 2). Pharmacokinetic parameters are shown in Table 3. In the two groups, C Max increased significantly from the first to the last injection, suggesting a cumulative effect. The increase in T Max between the first and the last injection was not significant in either group. C Max and T Max also did not differ between the groups. No morphine was given to the patients. Ten patients received dextropropoxyphene and paracetamol and one received salicylates as analgesic medication. The patients receiving these drugs were equally allocated to each group. Discussion Despite the statistically significant increase in FVC and the decrease in the VAS pain score following interpleural injection of bupivacaine and epinephrine in thoracotomy patients, our study showed that intrapleural analgesia was inefficient. The VAS score following intrapleural analgesia decreased only to 4 or 5, which is the severity of pain usually required to include patients in clinical analgesia trials.7 Thus, pain relief was too poor to demonstrate the effectiveness of this technique. Only posterolateral thoracotomies were included in this study, since previous studies have shown that ante120
J. Clin. Anesth.,
vol. 5, March/April
1993
of bupivacaine
in both
groups
(means
it SD).
Table 2. Heart Rate (HR) and Mean Arterial Pressure (MAP) Variations following Injections in Groups 1 and 2 Group 1 HR &pm) Before After MAP (mmHg) Before After *Significantly different
Group 2
97 2 13 97 f 13
91 t 24 91 ? 24
104 * 12 101 f 12
94 -r- 12* 93 r to*
from Group 1; p < 0.01.
Note: Data are means 2 SD. Before = before injection; after = following injection.
Table 3. Pharmacokinetic Parameters of Bupivacaine 100 mg after the First and Last Injections in Both Groups Group 1
Group 2
0.75 Y?0.57 2.11 * 0.71*
0.42 + 0.29 1.53 t 0.60*
25 + 11 39 + 9
23 ? 14 33 t 8
C Max (kg/ml)
First injection Last injection T Max (min) First injection Last injection
*Significantly higher than after the first injection; p < 0.01. Note: Data are means t SD. C Max = maximum peak concentration; T Max = maximum time to reach peak concentration. rior thoracotomy pain is not relieved with intrapleural analgesia.4 Intrapleural bupivacaine produces an intercostal nerve block, and distribution of local anesthetic solution is determined by gravity in the dependent area of the pleural space.* To maintain the intrapleural distribution of bupivacaine, we did not include patients with total pneumonectomy in the study, and to favor a paravertebral block, we gave injections to patients in the semi-
Interpleural
recumbent position .g Loss of drug via chest tubes was prevented by clamping for 10 minutes following injection.s,6 We used bupivacaine with epinephrine to lower the maximum peak concentration.4 We selected a total dose of bupivacaine 100 mg for each injection based on the initial reports of interpleural analgesia for cholecystectomy: Seltzer et al.10 obtained a high plasma maximum peak concentration (2.07 kg/ml) with a dose of 150 mg, and Stramskag et al. I1 found a lower plasma concentration (1.20 pg/ml) with a dose of 100 mg. Groups 1 and 2 were comparable in height and weight. To administer the same total dose at each injection to both groups, we used 0.5% and 0.25% bupivacaine. No difference was observed in percentage of pain variation between the groups, suggesting that concentration does not influence pain relief when the volume is different. Although intrapleural injection of bupivacaine decreased the VAS score, the efficacy of this technique remains questionable. The score was still too high for the injection to be considered effective6 and was comparable to that in other studies where opioids were used with intrapleural bupivacaine.3,7 The difference in pain score before injection between the two groups was probably related to the difference in patient ages. As with the pain score, FVC improved, but the mean increase was only 82 -+ 14 ml in Group 1 and 67 2 17 ml in Group 2. This seemed very low compared with the large increase in FVC obtained after intrapleural analgesia for cholecystectomy.12,13 To compare the plasma concentration between the first and the last injection, we measured bupivacaine on venous blood samples, since the arterial catheter in these patients is usually removed 24 hours postoperatively. Thus, the plasma concentration was lower than in studies using arterial blood samples.14 In our study, clamping of the chest tube was long enough to keep most of the drug effective. In fact, our plasma concentration was comparable to the venous concentration found after cholecystectomy in which no drug was lost.12 Following the first injection, the plasma concentration was similar in both groups. With equal doses and different concentrations and volumes, there was no change in C Max between the two groups, although C Max did increase from the first to the last injection. This cumulative effect precluded the use of higher bupivacaine doses. In summary, intrapleural analgesia with bupivacaine in a 10 ml or 20 ml solution and epinephrine was inef-
analgesia
with bupivacaine
after thoracotomy:
Elman
et al.
fective in relieving pain following thoracotomy for lung resection. However, with repeated pleural injections for a maximum time of 4 days, a cumulative effect was obtained, preventing us from testing higher doses.
References I. Reiestad F, Strijmskag KE: Interpleural catheter in the management of postoperative pain. A preliminary report. Reg An&h 1986;11:89-91. 2. McIlvaine WB, Knox RF, Fennessey PV, Goldstein M: Continuous infusion of bupivacaine via intrapleural catheter for analgesia after thoracotomy in children. Anesthesiology 1988;69:261-4. 3. Rosenberg PH, Scheinin BM, LepPntalo MJ, Lindors 0: Continuous intrapleural infusion of bupivacaine for analgesia after thoracotomy. Anesthesiology 1987;67:81 l-3. 4. Kambam JR, Hammon J, Parris WC, Lupinetti FM: Intrapleural analgesia for postthoracotomy pain and blood levels of bupivacaine following intrapleural injection. Can J Anaesth 1989;36: 106-9. 5. Covino BG: Interpleural regional analgesia. Anesth Analg 1988;67:427-9. 6. Dodson ME: The methodology of studies of postoperative pain and analgesia. In: Feldman SA, Scurr CF, eds. Current Topics in Anaesthesia Serzes. Vol. 8: The Management of Postoperative Pain. London: Edward Arnold, 1985:31-49. 7. Ferrante FM, Chan VW, Arthur GR, Rocco AG: Interpleural analgesia after thoracotomy. Anesth Analg 1991;72:105-9. 8. Riegler FX, VadeBoncouer TR, Pelligrino DA: Interpleural anesthetics in the dog: differential somatic neural blockade. Anesthesioloa 1989;71:744-50. 9. Strijmskag KE, Hauge 0, Steen PA: Distribution of local anaesthetics injected into the interpleural space, studied by computerized tomography. Acta Anaesthesiol &and 1990;34:323-6. 10. Seltzer JL, Larijani GE, Goldberg ME, Marr AT: Intrapleural bupivacaine-a kinetic and dynamic evaluation. Anesthesiology 1987;67:798-800. 11. Striimskag KE, Reiestad F, Holmqvist EL, Ogenstad S: Intrapleural administration of 0.25%, 0.375%, and 0.5% bupivaCaine with epinephrine after cholecystectomy. Anesth Analg 1988;67:430-4. 12. Brismar B, Pettersson N, Tokics L, Strandberg A, Hedenstierna G: Postoperative analgesia with intrapleural administration of bupivacaine-adrenaline. Acta Anaesthesiol &and 1987;31:515-20. 13. Frenette L, Boudreault D, Guay J: Interpleural analgesia improves pulmonary function after cholecystectomy. Can J Anaesth 1991;38:71-4. PO, et al: Arterial and 14. Moore DC, Mather LE, Bridenbaugh venous plasma levels of bupivacaine following epidural and intercostal nerve blocks. Anesthesiology 1976;45:39-45.
J. Clin.
Anesth.,
vol. 5, March/April
1993
121