Ann Thorac Surg 2004;77:284-288
© 2004 The Society of Thoracic Surgeons
Original article: general thoracic
Intermittent infusion of 0.25% bupivacaine through an intrapleural catheter for post-thoracotomy pain relief
Ömer Tet
k, MDa,
Fatih 
slamo
lu, MDa*,
Erhan Ayan, MDa,
Mehmet Duran, MDa,
Suat Buket, MDa,
Ahmet Çekrdekç, MDa
a Department of Cardiovascular Surgery, Atatürk Medical Research Hospital, 
zmir, Turkey
b Department of Cardiovascular Surgery, Ege University Medical Faculty, zmir, Turkey
c Department of Cardiovascular Surgery, Frat University Medical Faculty, Elaz
, Turkey
d Department of Cardiovascular Surgery, Frat University Medical Faculty, Elaz, Turkey
e Department of Thoracic and Cardiovascular Surgery, Kocatepe University Medical Faculty, Afyon, Turkey
Accepted for publication July 17, 2003.
* Address reprint requests to Dr Islamoglu, Ege Üniversitesi Tp Fakültesi, Kalp ve Damar Cerrahisi Anabilim Dal 35100 zmir, Turkey
e-mail: fislamoglu{at}hotmail.com
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Abstract
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BACKGROUND: The present study was designed to evaluate the effectiveness of intrapleural 0.25% bupivacaine delivered by intermittent infusions for post-thoracotomy pain relief.
METHODS: Forty patients undergoing elective lobectomy were randomly, but equally, placed into two groups. An intrapleural catheter was inserted under direct vision during surgery. Group I received intrapleural 40 mL of 0.25% bupivacaine, group II was administered 40 mL of saline solution as a control group. Diclofenac sodium was administered as an additional analgesic, if required. Postoperative pain was evaluated using a visual analog scale (VAS), and Prince Henry pain scale. Arterial oxygen saturation, heart rate, and systemic arterial pressures were monitored. All observations were recorded 5, 10, 15, 20, 25, and 30 minutes after the injection, and thereafter at hourly intervals through the postoperative 24 hours.
RESULTS: The mean analgesia times were 5 hours and 2 hours in group I and group II, respectively. Therefore, bupivacaine administrations were repeated every 6 hours in group I, and saline with additional analgesic were administered every 4 hours in group II. The heart rate and arterial pressures did not show a significant difference. While the additional analgesic requirement was 180 ± 10 mg/d in group II, there was no need for additional analgesic administration in the group I patients. Arterial oxygen was significantly higher in group I than in group II. Arterial carbon dioxide tension of group II was significantly higher than that of group I. While the postoperative atelectasis and pneumonia developed in four patients and one, respectively, in group II, no such complication was observed in group I.
CONCLUSIONS: The easy placement of an intrapleural catheter and better pain relief observed in the present study suggest that intermittent pleural infusion of 0.25% bupivacaine has proven to be a safe and effective method for relief of post-thoracotomy pain.
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Introduction
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Insufficient relief of post-thoracotomy pain is a major cause of increased rate of postoperative complications including inadequate coughing, mucous plugging, hypoxia, compromised ventilation, or even worse, if followed by bacterial colonization, parenchymal lung infection [1–4]. Various treatment modalities have been introduced for the management of post-thoracotomy pain. These include epidural analgesia, intercostal nerve blockade, cryoanalgesia, systemic use of opioids or nonsteroidal antiinflammatory drugs, and subarachnoid opioid administration [1, 2, 5]. Although parenteral use of opioids for pain management after thoracic surgery is an effective and reliable method, these agents are sometimes associated with respiratory depression, nausea, and bowel dysfunction. Intraoperative temporary or continuous intercostal nerve blockade through a subcostal incision provides a sufficient pain control, however it necessitates frequently addition of other analgesic drugs [1, 2]. Thoracic epidural administration of opioids is also effective in pain management, but carries a considerable risk for delayed respiratory depression. Nonsteroidal antiinflammatory drugs may cause gastrointestinal problems, acute renal failure, or platelet dysfunction [1, 2, 6]. The present study was designed to evaluate the effectiveness of administration of 0.25% bupivacaine which is a longer acting local anesthetic, through an intrapleural catheter placed easily without serious complication risk before the closure of the thoracotomy.
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Material and methods
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Forty patients undergoing elective lobectomy were included in this double-blind, randomized study, after written informed consent had been obtained and ethics committee approval had been given. Excluded were patients with a history of severe heart disease or hepatic or renal failure, patients undergoing resection of the pleura or chest wall, patients with hemorrhagic diathesis or medication of anticoagulants or acetylsalisilic acid, and patients with a known allergy to local anesthetic agents. Two randomized groups of 20 patients each were compared. One received intrapleural 40 mL of 0.25% bupivacaine (group I), the other was administered 40 mL of saline solution as control group (group II). The need for additional analgesic for any patient complaining of pain was fulfilled by administration of diclofenac sodium (intramuscular), and the time and frequency of these adminsitrations were recorded. Observations were made in the first 24 hours of the postoperative period. Preinduction of anesthesia was performed via intramuscular administration of 0.5 mg atropine and 5 mg droperidol, 30 minutes before the induction. Anesthesia was induced with IV 5 mg/kg thiopental and 1 mg/kg succinylcholine and was maintained with enflurane at 1% in oxygen-nitrogen protoxyde mixture (50:50) combined with vecuronium. At the time of rib approximation just before the chest closure, an 18 G intrapleural catheter was inserted through an intercostal space just beneath the one that thoracic incision was performed and was placed between parietal and visceral pleura under direct vision during surgery. First drug administration was performed after the verification of the patency of chest tubes following the chest closure. The catheter was removed 24 hours after the operation, before relocation of the patient from the intensive care unit to the surgical ward, provided there was no complaint of pain.
Postoperative pain was evaluated by a blinded anesthetist using a visual analog scale (VAS) graded from 0 (no pain) to -100 (worst pain imaginable), and a verbal rating scale (VRS-Prince Henry pain scale) (0 = no pain; 1 = mild; 2 = moderate; 3 = severe; 4 = unbearable) (Table 1,
Fig 3). Heart rate and systemic arterial pressures were monitored before the injection through the first 30 minutes after the injection. All observations were recorded whenever any patient complained of pain after the collecting of all data, 5, 10, 15, 20, 25, and 30 minutes after the injection, and thereafter at hourly intervals through the 24 hours after the operation. Patients were assessed as being in pain on the basis of either a VRS score of grade 3 or a VAS score greater than 60. Analgesia time defined the time interval between two consecutive recordings of the pain. The mean analgesia time defined the mean value of such recordings from the end of the operation to the postoperative 24th hour. Arterial oxygen saturation was continuously monitored by a pulse oxymeter. Moreover, arterial blood was sampled from the radial artery to measure blood gases at hourly intervals for postoperative 24 hours.
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Fig 3. Time course of Prince Henry pain scores. Scores on the Prince Henry pain scale were significantly higher in group II than in group I. * = p < 0.010; hatched bars = group I; white bars = group II.
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Statistical methods
Statistical analyses were performed by the SPSS/PC+ (ver 10.0) computer program. The probability (P) less than 0.05 was considered significant. Frequency and % values of categoric variables, and mean, average and standard deviation values of continuous variables were determined. Comparisons between groups for scoring data, beginning time, and duration of analgesia were conducted with Kruskal-Wallis analysis of variance (ANOVA). ANOVA for repeated measures was used to identify differences between groups in which the data were parametric and normally distributed. Within group changes were analyzed with ANOVA for repeated measures. Statistical analyses of parametric and demographic data were accomplished using the Student's t test for comparison of the two groups. Distributive data were tested with the 
-square analysis.
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Results
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There were 12 males and 8 females in group I (mean age: 71 ± 8 years), and 14 males and 6 females in group II (mean age: 68 ± 5 years). The characteristics of these patients are shown in Table 2.
There was no significant difference in the comparison of demographic characteristics between the two groups. The complete pain relief was achieved within 15 to 30 minutes in both groups and VAS scores significantly reduced within the first 30 minutes of the postoperative period (Fig 1). The mean analgesia times were 5 hours ± 1.51 hours (3 hours to 8 hours) and 2 hours ± 1.42 hours (1 hour to 6 hours) in group I and group II, respectively (p < 0.001) (Fig 2).
Therefore, bupivacaine administrations were repeated every 6 hours in group I, and saline with additional analgesic (diclofenac sodium) were administered every 4 hours in group II. The similarity between the time courses of VAS scores of the two groups over the first 2 hours indicated the recovery period from anesthetic management. While the heart rate and arterial pressures of group I showed 20% and 10% reductions, respectively, the reductions in the heart rate and arterial pressures of group II were 17% and 8%, respectively, without a significant difference, through the first 30 minutes after the injection. While the additional analgesic requirement was 180 ± 10 mg/d in group II, there was no need for additional analgesic administration in group I. Arterial oxygen was significantly higher in group I (95.05 ± 5.44 mm Hg) than in group II (79.50 ± 5.85 mm Hg), and carbon dioxide tension of group II (46.70 ± 2.01 mm Hg) was significantly higher than that of group I (42.30 ± 2.56 mm Hg) in the blood gas analyses, especially at 4 hours (p < 0.001). Moreover, the oral food and water intake of patients in group I was significantly better than that in group II. Postoperative atelectasis and pneumonia developed in the four patients and one patient, respectively, in group II. All four patients with atelectasis completely recovered by respiratory rehabilitation and continuous positive airway pressure (CPAP) ventilatory support. Pneumonia in one patient was also treated without any sequela by an effective antibiotic management. There was no systemic complication or mortality in both groups. Although the mean duration of the stay in the hospital of group II was longer than that of group I, the difference did not achieve statistical significance.
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Fig 1. Time course of visual analog pain scores. Scores on the visual analog pain scale were significantly higher in group II than in group I, especially at 4 hours. * = p < 0.010; open box = group I; closed box = group II.
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Fig 2. Distribution of patients in both groups according to analgesia times. The mean analgesia times were significantly longer in group I than in group II (p < 0.001).
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Comment
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Effective pain management is one of the most important components of the treatment of patients undergoing thoracic surgery [2]. Post-thoracotomy pain is one of the most severe types of postoperative pain during the first 24 hours of the postoperative period and is responsible for postoperative morbidity and mortality by compromising respiratory functions [1, 2]. Because of the limitations of former analgesic techniques, including respiratory depression with epidural opioid analgesia, short duration of action, or lack of efficacy with other additional analgesic administrations which was also seen in our study, interest in the administration of long-acting anesthetic agents through an intrapleural catheter has recently moved center [7, 8]. Although thoracic epidural analgesia has been shown as the gold standard method for providing highly effective control of postoperative pain, it may not be suitable especially in patients suffering from a coagulation disorder. Furthermore, this technique requires considerable experience [9]. Potential serious complications, such as dural puncture, bleeding, hematoma, and infection at the catheter implantation site need to be taken into consideration with this technique [10, 11]. Some serious complications which can lead to a fatal outcome, such as delayed respiratory depression, and a number of uncomfortable side effects, such as urinary retention, bradycardia, hypotension, and opioid induced pruritus may be observed after the administration of epidural opioids [2, 12].
Intercostal nerve blockade has recently come into practice as an alternative technique for management of post-thoracotomy pain. However, the uncomfortable status of a patient because of serial injections and long-term intercostal neuralgia have been reported as disadvantages of this technique [13]. Parenteral opioids or nonsteroidal antiinflammatory drugs are also currently used for pain management after thoracic surgery. Although opioids have an effective potential for reliable pain relief, these agents can cause some serious pulmonary complications, such as respiratory depression [1]. Systemic use of nonsteroidal antiinflammatory drugs is another proposed method, however, it often does not provide satisfactory pain relief. Inadequacy of these drugs in pain management was also observed in the present study. Moreover, potential complications of nonsteroidal antiinflammatory drugs, such as gastrointestinal bleeding and acute renal failure, need to be taken into consideration [2].
Another alternative which has been introduced recently, with very promising results, is the method of diffuse intrapleural analgesia performed by infusion of a local anesthetic through a catheter positioned inside the pleural cavity [14]. The mechanism of action appears to be diffusion across the parietal pleura [15]. Although interpleural analgesia is the more correct terminology to describe this anesthetic technique, since the catheter lies between the parietal and visceral pleura [16], the term "intrapleural analgesia" has been used synonymously. Some previous studies have shown limited or no improvement in analgesia with this technique [16–19]. Scheinin and colleagues compared patients who received interpleural analgesia plus oxycodone supplementation with a control group of patients who received systemic oxycodone alone; a decrease in opiate consumption which was seen in the interpleural group during the first postoperative day, but not over a 48-hour period [17]. Schneider and colleagues observed no subjective or objective clinical benefit of interpleural analgesia [18]. Silimon and colleagues also found no analgesic efficacy in patients undergoing anterolateral and posterolateral thoracotomies when comparing patients receiving either interpleural bupivacaine or saline [16]. Kambam and colleagues reported that interpleural analgesia was effective in patients receiving posterior and lateral thoracotomy but not in ones receiving anterior thoracotomy [19]. Some possible mechanisms were included in the limitation of the efficacy of interpleural analgesia, such as loss of local anesthetic through the chest tube; dilution of local anesthetic with blood and exudative fluid accumulated in the pleural cavity; altered diffusion across the parietal pleural following surgical manipulation and inflammation; and binding of local anesthetic with proteins [16, 20].
On the contrary to these discouraging results, Semsroth and colleagues reported that continuous intrapleural infusion of 0.25% bupivacaine provided an effective analgesia as a safe and suitable method for pain relief in infants and children following thoracotomy [21]. The present study was also designed to evaluate the effectiveness of intrapleural 0.25% bupivacaine delivered by intermittent infusions instead of continuous infusion as a different administration method from that of a former study for post-thoracotomy pain relief. Easy management without a need for considerable experience, comfort of the patient without any serious complication risk, are advantages of intrapleural analgesia [21]. The results of our study showed that intrapleural analgesia provided more effective and longer active pain control in group I than nonsteroidal antiinflammatory drugs administered in group II, on the VAS and Prince Henry pain scale scores (Figs 1 and 3) . In addition to nonsteroidal antiinflammatory drugs (Diclofenac sodium), patients in group II had received only saline solution to make a control group. However, an effective and reliable pain control provided by 0.25% bupivacaine in group I could not be observed in control group. Not once was any additional analgesic required for patients in group I. Semsroth and colleagues also reported that only one child who was treated with bupivacaine required a supplementary dose of an opioid. In the present study, duration of analgesia and intervals between drug administrations were significantly longer in group I than those in control group (Fig 2). Postoperative pulmonary functions and arterial oxygen tensions of group I were also significantly superior than those of control group. While the postoperative atelectasis and pneumonia developed in four patients and one in control group, no complication was observed in group I.
In comparison with other methods including epidural analgesia, intercostal nerve blockade, and parenteral use of opioids or nonsteroidal antiinflammatory drugs, besides better pain control, the most important superiority of intrapleural bupivacaine administration seems the lack of any recognizable side effect or complication which could be seen in other techniques. In the present study, bupivacaine was administered in a dosage about twice as much as that in former studies, in an attempt to replace the loss of agent through chest tubes during the postoperative period.
In conclusion, the lack of any technical challenge or complication related to intrapleural catheter insertion and better pain relief observed in the present study suggest that intermittent pleural infusion of 0.25% bupivacaine has proven to be a safe and effective method for relief of post-thoracotomy pain.
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Abstract
Introduction
