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Anesth Analg 2000;91:44-50
© 2000 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

Interpleural Analgesia Does Not Influence Postthoracotomy Pain

Malte Silomon, MD*, Thorsten Claus, MD*, Hanno Huwer, MD{dagger}, Andreas Biedler, MD*, Reinhard Larsen, MD*, and Gerd Molter, MD*

Departments of *Anesthesiology and Critical Care Medicine and {dagger}Thoracic and Cardiovascular Surgery, University of Saarland, Homburg/Saar, Germany

Address correspondence and reprint requests to Malte Silomon, MD, Department of Anesthesiology and Critical Care Medicine, University of Saarland, 66421 Homburg/Saar, Germany. Address e-mail to aimsil{at}med-rz.uni-sb.de


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
The management of postthoracotomy pain is a problem and may contribute to atelectasis, leading to hypoxemia, pulmonary infection, and permanent alveolar damage. We sought to determine the efficacy of interpleural analgesia for pain control and to evaluate independent predictors for postoperative pain intensity. Eighty-three patients undergoing elective anterolateral (n = 37) and posterolateral (n = 46) thoracotomy were included in a prospective, randomized, double-blinded trial. Patients were assigned to receive either 0.5% bupivacaine or saline solution interpleurally every 4 h for 10 doses postoperatively. All patients also received patient-controlled analgesics (PCA) with piritramide as the opioid for additional pain control. Pain was assessed on the basis of PCA requirements and by using a visual analog scale. Visual analog scale scores and PCA requirements were not different between groups. Both interpleural bupivacaine and saline significantly reduced pain scores 30 min after the administration. We concluded that pain reduction by interpleural instillation of bupivacaine reflects a placebo-like effect; however, interpleural analgesia is not effective in patients undergoing lateral thoracotomy. Sex and surgical approach were shown to influence postoperative pain intensity at rest, but not during coughing. The female patients, and those undergoing posterolateral thoracotomy, exhibited higher pain scores. This observation appears to be of only marginal clinical significance. The efficacy of interpleural analgesia to reduce postoperative pain intensity in patients after lateral thoracotomy is controversial. In this study we demonstrated a lack of efficacy of interpleural analgesia.

Implications: The efficacy of interpleural analgesia to reduce postoperative pain intensity in patients after lateral thoracotomy is controversial. In this study, we demonstrated a lack of efficacy of interpleural analgesia.


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Pain is the most important factor responsible for ineffective ventilation, ineffective cough, and impaired ability to sigh and breathe deeply, in patients after thoracic surgery. This may contribute to pulmonary atelectasis leading to ventilation/perfusion abnormalities and hypoxemia, as well as infection, after thoracotomy. Although analgesia has the potential to reduce pulmonary morbidity, most analgesic techniques carry the risk of concomitant complications associated with systemic drug administration or placement of catheters (e.g., epidural catheterization). Therefore, the choice of pain therapy in thoracotomized patients is complex and controversial (1).

Interpleural (IP) analgesia is induced by placing local anesthetic into the IP space which lies between the parietal and visceral pleurae. The previous terminology of intrapleural analgesia, which may have been generated to oppose the extrapleural analgesia, is used synonymously (2); however, it is anatomically incorrect, because local anesthetic is not placed into the pleura parietalis or visceralis. Interpleural analgesia produces regional analgesia of the chest wall and is used for pain therapy of different indications which include breast, renal, gall bladder and thoracic surgery, and chronic pain (3). In patients undergoing lateral thoracotomy, this technique has the advantage of intraoperative catheter placement under direct vision with a low risk for complications caused by catheterization. However, there is a controversy about its efficacy for pain relief after thoracotomy for pulmonary surgery (2,4).

We compared IP bupivacaine for postoperative pain treatment with placebo in a prospective, controlled, randomized, and double-blinded trial. Our objective was to determine whether IP bupivacaine affects postoperative pain relief, morbidity, and hospital stay. Furthermore, we analyzed the effects of sex and anterolateral or posterolateral approaches on postoperative pain.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
This study was approved by the institutional review board of the University of Saarland. Written, informed consent for participation was obtained from 93 patients who were admitted for lateral thoracotomy. Patients with an allergy to local anesthetics or piritramide, with postoperative air leak through the chest tubes, undergoing pleurectomy, having repeat thoracotomy, having full rib resection, or unable to cooperate were excluded from the study.

After premedication with diazepam, anesthesia was induced IV with 3 µg/kg fentanyl, 0.3 mg/kg etomidate and muscle relaxation with 0.5 mg/kg atracurium. The tracheas of all patients were intubated with a double-lumen endobronchial tube. Anesthesia was maintained with 50% nitrous oxide in oxygen and isoflurane supplementation as required. During one-lung ventilation, inspired oxygen concentration was increased to 100%. Intraoperative systemic analgesia was limited to fentanyl in unrestricted doses. Pulmonary operations were performed at the fourth or fifth intercostal space through a standard anterolateral or posterolateral thoracotomy, respectively. Anterolateral thoracotomy was performed through a curved submammary incision extending from the sternum anteriorly to the midaxillary line. Posterolateral thoracotomy extended from the anterior axillary line to a point midway between the vertebral spines and the vertebral border of the scapula (5). At the end of the surgical procedure, just before chest closure, the surgeon inserted an IP catheter percutaneously in the seventh intercostal space. The tip of the catheter was visually directed toward the fourth intercostal space on the paravertebral line.

After surgery, patients were ventilated with pressure support, all patients were tracheally extubated after rewarming, during the first 4 h after admission to the intensive care unit (ICU). After admission to the ICU, patients were randomly assigned into two groups. Just after, arrival patients in the bupivacaine group (Group B) received 20 mL (100 mg) bupivacaine 0.5%, whereas patients in the placebo group (Group P) received 20 mL saline 0.9%. Every 4 h thereafter, each group received the same medication for 10 repetitions. The contents of the syringes were prepared immediately before injection by a nurse who was not further involved in this investigation. Patients were kept in a supine position and chest tubes were clamped before injection of the study solution into the IP catheter. After 30 min, chest tubes were unclamped. When the patients were awake, they were encouraged to take supplementary doses of piritramide, an opioid analgesic with actions and uses similar to those of morphine. This was administered IV via a patient-controlled analgesia (PCA) device (Injectomat-CP PACOM; Fresenius, Bad Homburg, Germany). The PCA device was programmed to provide a bolus of 3 mg piritramide; the lockout time was 5 min. During the 30-min chest tube clamping, the PCA device was removed from the patient. Data collection was commenced with the second IP injection, when all patients were tracheally extubated and conversant. They were asked to assess the intensity of the chest pain, at rest and when coughing, using a visual analog scale (VAS) (0–100 mm; 0 = complete pain relief and 100 = unbearable pain) immediately before clamping the chest tubes and just after unclamping. At the same time, the piritramide demand within the elapsed 4 h was recorded. During the study period, patients were evaluated for systemic adverse effects (i.e., drowsiness, confusion, dizziness, and hallucinations). We further recorded length of ICU and hospital stay, complications, such as pneumonia and atelectasis, and demand for therapeutic bronchoscopy or reintubation.

The VAS scores of each patient were summarized as four VAS mean scores: Mean VAS at rest before injection (VAS r0), 30 min after injection of the study solution (VAS r30), when coughing before injection (VAS c0), and 30 min after injection of the study solution (VAS c30). The dose of analgesics administered was compared between Group B and Group P, anterolateral and posterolateral approaches, and male and female patients using the Mann-Whitney U-test. Differences in the mean VAS scores within the groups before and after the administration of bupivacaine and saline solution, respectively, were evaluated by using the Wilcoxon’s signed rank test. Differences between the groups for sex and postoperative complications were calculated by using the Fisher’s exact test. Differences in numeric demographic data (e.g., age, and body weight), ICU and hospital stay were analyzed by using the Mann-Whitney U-test. Three-way analysis of variance, followed by a multiple classification analysis, was performed to evaluate an influence of the surgical approach (anterolateral versus posterolateral), type of IP analgesic (bupivacaine versus placebo), and sex (male/female) on postoperative pain intensity (mean VAS scores) and supplemental opioid demand. To evaluate a possible role of dilution of the local anesthetic by pleural exudation, chest tube fluid loss and opioid consumption, and chest tube fluid loss and mean pain scores were correlated by using Pearson product moment correlation, respectively. A P < 0.05 was considered significant. All statistics were performed by using SPSS for Windows 8.0 (SPSS, Chicago, IL).


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Of the 93 patients, 10 were withdrawn, nine because of postoperative air leak and one because of reproducible dizziness after bupivacaine instillation. The remaining 83 patients participated in the study. There were no differences in sex, age, weight, surgical approach, surgery, intraoperative analgesics, and duration of one-lung ventilation between Groups P and B (Table 1).


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  		Table 1. Patient Characteristics, Operation Data, and Postoperative Complications
 
Mean pain scores were significantly reduced 30 min after IP instillation of bupivacaine 0.5% or normal saline, respectively. However, there was no difference between the groups when comparing mean pain scores at rest and when coughing either before or after the administration of the corresponding solution (Figure 1). When VAS scores were analyzed at each time point recorded, there were also no differences between the groups at any time of measurement (data not shown).



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  		Figure 1. Visual analog scale (VAS) mean scores before (open bars) and 30 min after (black bars) interpleural administration of normal saline (Group P) or bupivacaine (Group B), respectively. Treatment significantly reduced mean pain scores in both groups, however, no differences in pain scores were observed between Groups P and B. VAS mean scores are calculated from all occasions of VAS measurements after admission to ICU. *P < 0.01 versus before interpleural injection. Values are mean ± SD.

 
Three-way analysis of variance and multiple classification analysis showed a significant influence of sex and surgical approach on postoperative pain intensity at rest (VAS r0 and VAS r30), with the female patients and those undergoing the posterolateral approach exhibiting the higher pain scores. When coughing (VAS c0 and VAS c30) sex and surgical approach did not affect VAS scores, and the type of the solution given IP (bupivacaine or saline) did not modify the mean pain scores at any occasion of measurement (Figure 2). Supplemental opioid demand was not statistically significant, considering the route of surgical approach, kind of IP analgesic, or sex. However, when data were analyzed for the different sex and surgical approach groups, subgroups of sex were distributed unequally for body weight, resulting in a significantly larger piritramide consumption by the female patients when related to body weight (Table 2). There were no significant differences between the different IP-treatment groups in cumulative opioid consumption (Figure 3) and no correlation between pleural drain loss and opioid consumption (Figure 4) or pain scores (data not shown).



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  		Figure 2. Data present mean VAS ± SD and statistically expected mean VAS scores (exp. mean). Sex (f = female, m = male) and surgical approach (p = posterolateral, a = anterolateral) significantly influence the VAS scores at rest, but not during coughing. The treatment given interpleurally (p = placebo, b = bupivacaine) has no statistically significant effects on pain intensity. VAS r0 = at rest before injection; VAS r30 = at rest and 30 min after injection of the study solution; VAS c0 = during coughing, but before injection; VAS c30 = during coughing and 30 min after injection of the study solution. *P < 0.01, #P < 0.05.

 

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  		Table 2. Demographic Data and Piritramid Consumption for Different Sex and Approach Groups
 


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  		Figure 3. Cumulated piritramide consumption every 4 h during 36 h postoperatively. There were no differences between the groups. Values are mean ± SD; {square} = placebo group; {blacksquare} = bupivacaine group.

 


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  		Figure 4. Correlation analysis of chest tube fluid loss and opioid consumption during 36 h after admission to ICU. Dilution of the local anesthetic from pleural exudation or intrathoracic bleeding does not influence pain intensity as reflected by overall opioid demand. {square} = placebo group; {blacksquare} = bupivacaine group.

 
With regard to the outcome data, there were no significant differences between the IP-treatment groups comparing the incidence of adverse effects, such as pneumonia, atelectasis, bronchoscopic interventions, reintubations, and postoperative ICU and hospital stay (Table 1), although data were analyzed for sex and surgical approach subgroups (data not shown). Reintubation of five patients (Table 1) was necessary after the study was terminated. Four patients were reintubated in the bupivacaine group, two with impaired gas exchange, one with suspected pulmonary embolism, and one with chylothorax requiring repeat thoracotomy. One patient with pneumonia was reintubated in the placebo group.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
The aim of postoperative pain management is to provide good subjective comfort and to contribute to early recovery and a good outcome after surgery. After pulmonary resection, pain therapy with systemic opioids has the potential for a good pain relief at rest with a lack of effective pain reduction when coughing or breathing deeply. However, effective coughing is necessary for a sufficient bronchial clearance to prevent atelectasis and bronchopulmonary infection. Therefore, many attempts have been made to combine systemic drug administration with different kinds of regional anesthesia to improve postthoracotomy pain control (6).

Interpleural analgesia use has increased since publication of the investigation of Rosenberg et al. (7). The mechanism of action appears to be diffusion or bulk flow of local anesthetic into the subpleural space with a concomitant multiple segmental intercostal nerve block (8,9). If the catheter is placed intraoperatively under direct vision, this technique is safe and easy. Despite its wide use, systemic absorption and toxicity from local anesthetics have not been substantiated in clinical studies that assayed plasma levels, even when using larger amounts of bupivacaine than we administered (10). A disadvantage of this method for postthoracotomy patients is the inability to clamp the chest drains, because of risk of pneumothorax in patients with an air leak. Furthermore, Richardson et al. (11) showed a large chest tube loss of bupivacaine after IP administration, and there is evidence that IP local anesthetics may actively impair respiratory function through diaphragmatic and abdominal muscle weakness (11,12).

The current study indicated a significant pain reduction 30 min after IP injection of bupivacaine 0.5% and normal saline, respectively. Furthermore, we could not demonstrate any difference in mean VAS scores and PCA demand, at any time of measurement, for either solution given IP. Because VAS scoring was shown to be a valid measure of pain in the early postoperative period (13) these data appear to reflect a placebo effect of the IP injection. Our data are consistent with the work of Schneider et al. (10) who compared bupivacaine 0.5% (n = 9) with IP saline (n = 9) administered in 30 mL bolus every 4 h for a total of 12 doses after surgery. They also reported no differences in VAS pain scores and analgesic requirements between the groups. However, VAS pain scores were recorded on only two occasions during the study period raising the possibility that transient benefits 30 min after the administration may have been missed. Furthermore, supplemental analgesia was not standardized; patients received morphine sulfate or meperidine at their request. In contrast, Mann et al. (14) demonstrated reduced postoperative pain at 4, 24, and 72 h after 20 mL bupivacaine 0.25% IP every 4 h for 48–72 h compared with IP saline in patients undergoing posterolateral thoracotomy (n = 40). This study also exhibited no differences in opioid consumption between the groups and the difference in pain scores was not significant at 48 h.

In the current literature there are publications (2,4,10,14) providing evidence both supporting and opposing the effectiveness of the postoperative pain management via IP analgesia after thoracotomy. An explanation for insufficient pain reduction may be the loss of local anesthetics in the chest tubes (11) and altered diffusion within the parietal pleura after mechanical irritation by the surgical procedure. A dilution of the local anesthetics by pleural exudation appears to play a subordinate role because we could not demonstrate a relationship between chest tube fluid loss and analgesic requirement or pain scores. Because IP analgesia is reproducibly effective in patients with chronic pain (15), open cholecystectomy (16), or renal surgery (17) this technique should perhaps be reserved for these indications.

In the current study the posterolateral thoracotomy was shown to be the more painful approach at rest, before and after injection of the study solution. However, during coughing there was no influence of the surgical approach on postoperative pain scores. Because all surgical procedures were done by the same two surgeons, the increased pain may be explained by greater damage to the latissimus dorsi muscle (18) and more stress on the costovertebral joints, with wide rib retraction near the spinal column. These anatomical factors may contribute to the pain intensity at rest; however, they appear to have less influence during the dynamic process of coughing. When VAS scores on coughing are supposed to reflect the ability to cough, a clinical role of the surgical approach appears to be of only marginal significance. This conclusion is supported by our data, showing no differences in postoperative pulmonary complications based on insufficient bronchoalveolar clearance (e.g., pneumonia and atelectasis) dependent on the surgical approach.

The influence of sex on postoperative pain intensity and opioid demand when related to body weight is in accordance with recent studies showing sex to be an important variable in recovery from general anesthesia (19) and in remifentanil demand during surgery (20). The possible mechanisms leading to a higher opioid demand during surgery (20) and higher pain scores after surgery in women as shown in the current study are not fully understood (21). Because pain during coughing and therefore, the ability to cough, was not influenced by sex, a clinical relevance of sex differences appears to be questionable. This conclusion is supported by the outcome data showing no differences between male and female patients. However, further studies dealing with postoperative pain measurement should pay special attention to the distribution of sex within subsamples. When distributed unequally, sex should be incorporated into analysis of the dependent variables.

In conclusion, this study confirms the findings of prior investigators (4,10) that IP analgesia did not produce sufficient pain relief and cannot be recommended for sufficient pain control after lateral thoracotomy.


   Acknowledgments
 
We thank Vytas and Joanne Rupinskas for critically reading the manuscript and Olaf Lange for the help in statistical analysis.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Kruger M, Sandler AM. Post-thoracotomy pain control. Curr Opin Anaesthesiol 1999;12:55–8.
  2. McIlvaine WB. Intrapleural anesthesia is useful for thoracic analgesia. Pro: intrapleural anesthesia is useful for thoracic analgesia. J Cardiothorac Vasc Anesth 1996;10:425–8.[Web of Science][Medline]
  3. Murphy DF. Interpleural analgesia. Br J Anaesth 1993;71:426–34.[Free Full Text]
  4. Riegler FX. Intrapleural anesthesia is useful for thoracic analgesia. Con: unreliable benefit after thoracotomy-epidural is a better choice. J Cardiothorac Vasc Anesth 1996;10:429–31.[Web of Science][Medline]
  5. Moores DWO, Foster ED, McKneally MF. Incisions. In: Pearson FG, Deslauriers J, Ginsberg RJ, et al., eds. Thoracic surgery. New York:Churchill Livingston, 1995:113–29.
  6. Brodner G. Pain management in patients undergoing thoracic surgery. Curr Opin Anaesthesiol 1997;10:54–9.
  7. Rosenberg PH, Scheinin BMA, Lepantalo MJA, Lindfors O. Continuous intrapleural infusion of bupivacaine for analgesia after thoracotomy. Anesthesiology 1987;67:811–3.[Web of Science][Medline]
  8. McKenzie AG, Mathe S. Interpleural local anaesthesia: anatomical basis for mechanism of action. Br J Anaesth 1996;76:297–9.[Abstract/Free Full Text]
  9. Furuki I. Diffusion of bupivacaine into the intercostal muscle following interpleural analgesia. Masui 1997;46:1299–304.[Medline]
  10. Schneider RF, Villamena PC, Harvey J, et al. Lack of efficacy of intrapleural bupivacaine for postoperative analgesia following thoracotomy. Chest 1993;103:414–6.[Abstract/Free Full Text]
  11. Richardson J, Sabanathan S, Shah RD, et al. Pleural bupivacaine placement for optimal postthoracotomy pulmonary function: a prospective, randomized study. J Cardiothorac Vasc Anesth 1998;12:166–9.[Web of Science][Medline]
  12. Gallart L, Gea J, Aguar MC, et al. Effects of interpleural bupivacaine on respiratory muscle strength and pulmonary function. Anesthesiology 1995;83:48–55.[Medline]
  13. DeLoach LJ, Higgins MS, Caplan AB, Stiff JL. The visual analog scale in the immediate postoperative period: intrasubject variability and correlation with a numeric scale. Anesth Analg 1998;86:102–6.[Abstract]
  14. Mann LJ, Young GR, Williams JK, et al. Intrapleural bupivacaine in the control of postthoracotomy pain. Ann Thorac Surg 1992;53:449–54.[Abstract]
  15. Ramajoli F, DeAmici D. Is there a bilateral block of the thoracic sympathetic chain after unilateral intrapleural analgesia? Anesth Analg 1998;87:360–7.[Abstract/Free Full Text]
  16. Pettersson N, Perbeck L, Brismar B, Hahn RG. Sensory and sympathetic block during interpleural analgesia. Reg Anesth 1997;22:313–7.[Medline]
  17. Kaukinen S, Kaukinen L, Kataja J, et al. Interpleural analgesia for postoperative pain relief in renal surgery patients. Scand J Urol Nephrol 1994;28:39–43.[Medline]
  18. Hazelrigg SR, Landreneau MD, Boley TM. The effect of muscle sparing versus standard posterolateral thoracotomy on pulmonary function muscle strength and postoperative pain. J Thorac Cardiovasc Surg 1991;101:394–401.[Abstract]
  19. Gan TJ, Glass PS, Sigl J, et al. Women emerge from general anesthesia with propofol/alfentanil/nitrous oxide faster than men. Anesthesiology 1999;90:1283–7.[Web of Science][Medline]
  20. Drover DR, Lemmens HJM. Do women require higher remifentanil plasma concentrations than men [abstract]? Anesthesiology 1997;87:A306
  21. Giles BE, Walker JS. Gender differences in pain. Curr Opin Anaesthesiol 1999;12:591–5.[Medline]
Accepted for publication March 29, 2000.




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Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press