Asian Cardiovasc Thorac Ann 2008;16:370-374
© 2008 Asia Publishing EXchange Ltd
Interpleural Morphine vs Bupivacaine for Postthoracotomy Pain Relief
Shideh Dabir, MD,
Tahereh Parsa, MD,
Badiozaman Radpay, MD,
Mojgan Padyab, BS1
Department of Anesthesiology
1 Department of Biostatistics, National Research Institute of Tuberculosis and Lung Disease, Dr. Masih Daneshvari Hospital, Shahid Beheshti University, MC, Tehran, Iran
For reprint information contact: Shideh Dabir, MD Tel: 98 21 2010 9644 Fax: 98 21 2010 9644 Email: shdabir{at}yahoo.com, Department of Anesthesiology, National Research Institute of Tuberculosis and Lung Disease, Dr. Masih Daneshvari Hospital, Darabad, Niavaran, Tehran 1955841452, Iran.
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ABSTRACT
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This prospective randomized double-blind trial was designed to compare the analgesic effects of interpleural bupivacaine and interpleural morphine for postthoracotomy pain management. Thirty-six American Society of Anesthesiologists class I and II patients undergoing an elective posterolateral thoracotomy were randomly divided into 2 groups of 18 each. Before chest closure, an interpleural catheter was inserted under direct vision. At the end of the operation and every 4 hours thereafter, they received either 0.25% bupivacaine with epinephrine or 0.2 mg·kg–1 morphine sulfate interpleurally for 24 hours. The chest tubes were clamped during injection and for 15 min afterwards. Supplementary doses of intravenous morphine were given on request. The pain severity was evaluated at rest and on coughing before and 30 min after each interpleural injection, using an 11-point visual analog scale. Supplemental analgesic consumption and side effects were recorded. Both interpleural morphine and bupivacaine significantly reduced pain scores 30 min after each injection. However, pain scores and supplementary analgesic requirements were significantly lower in the interpleural morphine group. No serious side effects were detected in either group. Interpleural morphine provides better pain control than interpleural bupivacaine after a posterolateral thoracotomy.
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INTRODUCTION
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Thoracotomy causes severe pain in the postoperative period, which is intensified by respiration and coughing. Postthoracotomy pain can impair a patient’s ability to breathe deeply and cough effectively, leading to atelectasia and pulmonary complications. Epidural analgesia is the most effective of the various techniques to control postthoracotomy pain, but peripheral nerve block methods, such as interpleural analgesia, have been applied when epidural analgesia is contraindicated or presents a technical challenge. Interpleural regional analgesia is induced by injecting a drug into the interpleural space through a catheter placed between the parietal and visceral pleura. The mechanism of action appears to be diffusion of the drug through the parietal pleura and intercostal muscle to the intercostal space, with ipsilateral blockade of multiple intercostal nerves.1,2 Bupivacaine has been studied most often for relieving pain after thoracic operations. Little has been reported about its side effects or technique-related complications.1 However, with the discovery of local opioid receptors in peripheral tissues, attention has focused on the peripheral effects of opioids through the interpleural route.3,4 These appear to be caused via opioid receptors located on the intercostal nerves, producing unilateral analgesia.5,6 This may have the advantage of fewer opioid-related side effects. The goal of this study was to compare the efficacy of intermittent administration of interpleural morphine 0.2 mg·kg–1 and 30 mL of 0.25% bupivacaine for postthoracotomy pain treatment. The dosages of morphine and bupivacaine were chosen on the basis of previous observations.2,6,7
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PATIENTS AND METHODS
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This prospective randomized double-blind study was approved by the hospital ethics committee, and informed consent was obtained from each participating patient. Thirty-six American Society of Anesthesiologists class I and II patients undergoing an elective posterolateral thoracotomy were assigned to a bupivacaine or morphine group of 18 each, using a preoperative random allocation list (closed-envelope technique) generated from a random number table. An envelope was blindly drawn each time an eligible participant entered the trial. Exclusion criteria were age < 14 years, empyema, severe pleural adhesions and fibrosis, bullous emphysema and postoperative air leak through the chest tubes. Those unable to cooperate, opium addicts, and patients allergic to local anesthetics were also excluded. There were 25 men and 11 women, their mean age was 41 ± 15 years (range, 17–74 years), weight 68 ± 13 kg, and height 166 ± 9 cm. With the exception of weight, there were no significant differences in demographic characteristics between groups (Table 1
).
Oral diazepam 10 mg was administered to all patients the night before surgery. General anesthesia was induced with midazolam 1–2 mg, fentanyl 100–150 µg, sodium thiopental 5 mg·kg–1 and atracurium 0.6 mg·kg–1. The patients were intubated with a double-lumen endobronchial tube. Anesthesia was maintained with halothane in oxygen and atracurium. Bolus doses of fentanyl were given intraoperatively as an analgesic supplement when signs of sympathetic stimulation occurred despite sufficient depth of anesthesia. The last fentanyl dose was injected 30 min before the end of surgery, if needed. Before chest closure, the surgeon inserted a 20-gauge epidural catheter (Epidural minipack system 2; Portex Ltd, Hythe, UK) percutaneously via a Tuohy needle in one intercostal space above the incision site. The catheter tip was placed in the bullous pleural space on emphysema and the paravertebral groove, under direct vision, and loosely sutured to the parietal pleura and skin. With the patient supine, after closure of the chest and prior to tracheal extubation, the chest tubes were clamped and 1 of 2 identical syringes of the trial solutions was injected into the pleural cavity via the interpleural catheter. Patients in the bupivacaine group received 30 mL of 0.25% bupivacaine hydrochloride with 1:200,000 epinephrine in 10 mL of saline, while those in the morphine group received 0.2 mg·kg–1 morphine sulfate in 40 mL saline. The chest tubes were kept clamped for 15 min after interpleural injection while the patients remained in the supine position. All patients were extubated in the operating room and transferred to the intensive care unit. Similar interpleural bolus injections were repeated every 4 hours during the 1st 24 hours postoperatively. Upon the patient’s spontaneous request, supplementary doses of intravenous morphine were also given in increments of 1 mg until they expressed satisfaction.
Patients were asked to evaluate the severity of thoracotomy pain at rest and when coughing, using an 11-point (0 = no pain, 10 = the worst possible pain) visual analog scale (VAS) before and 30 min after interpleural injections at 4, 8, 12, 16, 20 and 24 hours postoperatively. Additional analgesia was not given during the first 30 min after each interpleural injection. Analgesia was considered effective if the VAS score obtained 30 min after interpleural injection was 
3. Side effects of interpleural drugs (i.e. toxic reactions to bupivacaine, sedation degree, nausea, vomiting, respiratory depression, pruritus and rash) were recorded during the 24-hour study period. Sedation was assessed using a 5-point scale: 1 = fully awake, 2 = drowsy, 3 = eyes closed but could be roused on command, 4 = eyes closed but could be roused by mild physical stimulation, 5 = eyes closed and could not be roused by mild physical stimulation. Total supplemental morphine dose, sedation score and chest tube drainage were calculated for each patient. The drug syringes were prepared by anesthesia technicians who did not participate in the study.
The sample size of 18 patients per group was calculated with a power of 80% to detect a VAS score point difference of 1.5 between the 2 study groups, with a significance level of 5%. Data analyses were performed using SPSS version 11.50 for Windows (SPSS, Chicago, IL, USA) and Microsoft Excel 2002. The independent-samples Student t test was used for continuous data, and the chi-squared test was applied to categorical data. Differences in mean VAS scores between groups before and after administration of interpleural drugs were evaluated using Wilcoxon’s signed-rank test. Comparisons of mean VAS and sedation scores were performed with the Mann-Whitney U test. Repeated-measures analysis of variance was carried out to analyze the effect of time on VAS scores. Covariance analysis was used to adjust the effect of weight on total supplemental morphine dosage. Data are given as mean ± standard deviation. A value of p < 0.05 was considered significant.
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RESULTS
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Surgical data and intraoperative fentanyl use were similar in both groups (Table 1
). No patient received supplemental analgesia in the hour prior to interpleural administration. Visual analog scale scores were significantly reduced 30 min after injection of both drugs. Intergroup comparison revealed that VAS scores were significantly lower in the morphine group at 4, 8, 12, 16, 20, and 24 hours postoperatively (Figure 1). Analgesia was effective (VAS 3) in more patients in the morphine group than the bupivacaine group at most time points. Visual analog scale scores over the 7 time points showed that pain intensity decreased over time in both groups. Supplemental morphine use was significantly less often in the morphine group than the bupivacaine group (Table 1). This difference was also noted when the supplemental dose of morphine was calculated per kilogram of body weight. The number of patients who received intravenous morphine supplementation was significantly less in the morphine group than the bupivacaine group (9 vs 16). There were no serious side effects. Two patients in the morphine group developed transient pruritus without any need for treatment. No significant difference in sedation scores was found between the groups at any time after surgery (Table 1). No catheter-related complications were noted.
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Figure 1. (a) Visual analogue scores (VAS) at rest and (b) with coughing before and 30 min after interpleural injection of morphine and bupivacaine; in both groups, there was a significant decrease in VAS scores 30 min after interpleural injection at 4, 8, 12, 16, 20, and 24 hours after thoracotomy. *No significant differences between groups. VASr0 = VAS at rest before injection, VASr30 = VAS at rest 30 min after injection. VASc0 = VAS on coughing before injection, VASc30 = VAS on coughing 30 min after injection.
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DISCUSSION
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These data show a superior analgesic effect of interpleural morphine compared to interpleural bupivacaine. Because of this and the lack of serious side effects, we consider that morphine can be recommended in preference to interpleural bupivacaine for pain relief after thoracotomy. Aykaç and colleagues6 found patients receiving intravenous morphine had higher plasma morphine levels as well as a higher rate of serious adverse effects than those receiving interpleural morphine. Our previous studies found a low and clinically insignificant incidence of side effects related to interpleural opioids.7,8
After thoracotomy, effective pain relief reduces the risk of atelectasis and pulmonary infection. However, many analgesic techniques carry the risk of major systemic side effects or complications associated with invasive procedures (e.g. epidural analgesia). Interpleural analgesia has gained popularity because of its low rate of complications. Local anesthetics as well as opioid agents administered via a catheter placed inside the pleural cavity have been used to anesthetize intercostal nerves to relieve pain after thoracotomy. If the interpleural catheter is placed intraoperatively under direct vision, this technique is safe and easy without the technical difficulties that may present during epidural catheter placement. Interpleural bupivacaine has become widely used after thoracic surgery; however, controversy still exists concerning its efficacy, although most studies have shown good results.9–14 Tetik and colleagues13 observed better pain relief with intermittent pleural infusion of 0.25% bupivacaine compared to interpleural saline. In contrast, several studies have shown limited efficacy of this analgesic method.15–17 Elman and colleagues15 found insufficient pain relief with interpleural bupivacaine after posterolateral thoracotomy, despite high plasma bupivacaine levels. Negative results may be related to loss of anesthetic through thoracic tubes, dilution of local anesthetic by pleural blood and secretions, altered diffusion across the parietal pleura because of surgical manipulation and inflammation, and failure to clamp the chest tube before administration of anesthetic.9,18
Opioids administered by various routes are still the mainstay of analgesia for postthoracotomy pain management. However, systemic opioids have the potential for good pain relief at rest with a lack of effective pain reduction when coughing or breathing deeply. In addition, opioids may cause adverse effects such as respiratory depression, somnolence, prolonged nausea or vomiting and pruritus, when administered via a systemic or epidural route. Patients receiving epidural narcotics may also need care in a setting that monitors their respiration. Adverse effects seen with systemic and epidural opioids may be avoided when using opioids interpleurally.
The results of our study support other positive results with interpleural administration of opioids in patients undergoing a thoracotomy.6–8,19 Karakaya and colleagues19 found that interpleural bupivacaine and fentanyl combined with epinephrine improved pain relief more than interpleural bupivacaine alone. Aykaç and colleagues6 observed interpleural morphine 20 mg to be more effective than the same dose given intravenously. Similarly, our previous studies found significant pain reduction following interpleural administration of opioids after posterolateral thoracotomy.7,8 On the other hand, Welte and colleagues5 noted that 2.5 mg of interpleural morphine did not reduce postthoracotomy pain intensity, but this dose of morphine was too low. Dilution of morphine in the pleural space and drainage of the drug from the chest tubes may lead to a lower concentration of drug at the receptor sites and insufficient pain relief. Furthermore, our results indicate that interpleural morphine may offer satisfactory analgesia for thoracic surgery in patients who are not suitable candidates for epidural analgesia, and it avoids complications associated with systemic opioids. However, it will be more valuable to compare the efficacy of interpleural morphine with a standard analgesic method likely to have higher efficacy (e.g. epidural analgesia), which will be significant if similar efficacy can be achieved with this much less invasive technique.
It was concluded that interpleural morphine gives better pain relief than interpleural bupivacaine after a posterolateral thoracotomy. The safety and effectiveness of interpleurally administered morphine makes it a suitable alternative to interpleural bupivacaine for analgesia after thoracotomy.
Presented as the poster at the International Anesthesia Research Society 80th Clinical and Scientific Congress, San Francisco, California, USA, March 24–28, 2006.
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REFERENCES
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ABSTRACT
INTRODUCTION
