Intercostal nerve blocks with bupivacaine significantly reduced postoperative pain scores compared with intercostal saline or no intercostal LA, when administered as single blocks (three43–45 of four46 studies), or repeat blocks (two22,47 of three46 studies) or as a continuous infusion (one study48) (Table 1). Intercostal nerve blocks were also associated with significantly reduced supplementary analgesic requirements when administered as repeat blocks (two22,47 of three46 studies) and continuous infusion (one study48), but not as a single intraoperative block (four43–46 of four studies) (Table 1).
Ten studies compared interpleural LA (bupivacaine or lidocaine) with systemic opioid analgesia,22,49–57 and two studies compared interpleural morphine with IV morphine,58,59 and these showed inconsistent results for postoperative pain scores and analgesic use (Table 1).
Quantitative analyses demonstrated that paravertebral bupivacaine reduced the incidence of hypotension compared with thoracic epidural bupivacaine (Fig. 6).
The only study that compared thoracic paravertebral block with bupivacaine versus intercostal nerve block with bupivacaine showed no significant difference between groups for pain scores or supplementary morphine use62 (Table 2).
There were no significant differences in pain scores or rescue morphine use in the only study that compared patients receiving repeated boluses of intrathecal morphine and those receiving thoracic epidural bupivacaine plus fentanyl, as a bolus and then infusion68 (Table 2).
Comparisons of single intercostal nerve block with bupivacaine versus thoracic epidural analgesia with bupivacaine or morphine in four studies showed mixed results for pain scores, and three69–71 of the four62 studies showed an increase in opioid requirements with intercostal nerve block (Table 2). Three studies22,69,70 comparing repeat intercostal nerve blocks using bupivacaine versus thoracic epidural analgesia using bupivacaine or morphine found no difference between groups in pain scores for 24 h after surgery, or in supplementary analgesic use (Table 2). However, one study found that pain scores were higher with a continuous infusion intercostal nerve block with bupivacaine compared with thoracic epidural bupivacaine72 (Table 2).
No meta-analyses of pain scores could be performed for the comparison of intercostal nerve blocks with thoracic epidural analgesia because of heterogeneity in the reporting of data (i.e., different times of measurement of pain scores; reporting of median and range, rather than mean and sd). However, a scatter plot shows that pain scores tended to be marginally higher at day 1 or 24 h after intercostal nerve blocks (Fig. 7).
Although thoracic epidural analgesia is commonly cited as the gold standard for postthoracotomy pain treatment,5,88,89 a review of other available regional techniques was warranted because epidural techniques may not always be possible and are associated with complications, including hypotension, and a risk of epidural hematoma and nerve injury.90 In a recent meta-analysis, paravertebral block provided comparable pain relief to epidural analgesia, with a superior side effect profile.6 Alternative regional techniques also require evaluation, since systemic analgesia has often proven to be insufficient for pain relief when used alone.88
Many alternative protocols have been studied in regional analgesic techniques, and therefore it is sometimes difficult to draw definite conclusions. Epidural analgesia, for example, can be performed with LA, opioid or both. Intercostal blocks can be performed as single, repeated or continuous injections with short- or long-acting LA. This limits the studies with homogeneous design from which data can be pooled. Nevertheless, the analyses performed allow us to put forward recommendations for pain treatment after thoracotomy that consider both analgesic efficacy and side effects (Fig. 8).
Evidence from this review supported the efficacy of thoracic epidural combining LA plus opioid, as well as thoracic epidural LA alone and thoracic epidural lipophilic opioid (e.g., fentanyl) alone for thoracotomy. In agreement with another systematic review comparing epidural with systemic analgesia in various procedures,91 thoracic epidural hydrophilic opioid (e.g., morphine or nicomorphine) did not show overall benefit over systemic opioids. Further well designed studies are needed to determine the most effective components of epidural solution. Overall, however, the most consistently effective analgesia was provided by continuous infusion of thoracic epidural combining LA plus opioid (Table 1).14–21 This combination is believed to provide synergistic analgesia, requiring smaller doses and thus fewer side effects.92 Thoracic epidural infusion of LA plus opioid is recommended, and may be started in the pre-/ intraoperative period and continued for 2–3 days after surgery, since this was the duration of epidural analgesia in the majority of positive studies. Addition of epinephrine to low-dose thoracic epidural LA improved analgesia in several studies,93–95 but further investigation is necessary to confirm this point, particularly in thoracic surgery. Lumbar epidural analgesia has also been studied in thoracotomy, but thoracic epidural LA plus opioid is recommended due to the consistency of evidence supporting its use; a comparison of the efficacy of epidural analgesia via the different sites of administration is beyond the scope of this review.
Thoracic paravertebral block with LA, as a bolus and continuous infusion for 2–3 days, is also recommended, based on evidence that the technique provides comparable analgesia to thoracic epidural with LA alone, and may be associated with fewer adverse effects, including hypotension, nausea and urinary retention.60–64 Quantitative analyses found that thoracic paravertebral block reduced the incidence of pulmonary complications compared with systemic analgesia, whereas thoracic epidural analgesia did not. These findings support the results of the meta-analysis of Davies et al., which showed reduced pulmonary morbidity with thoracic paravertebral block compared with epidural analgesia.6 In another systematic review, epidural analgesia did reduce pulmonary morbidity in high-risk patients compared with systemic analgesia, but this analysis was not procedure-specific.96 Due to the limited thoracotomy-specific data on pulmonary morbidity from studies using different regimens of epidural analgesia, and since transferable evidence shows advantageous effects of epidural analgesia, the choice between epidural and paravertebral techniques should not depend on the currently limited evidence for a reduction of pulmonary morbidity. Three studies directly compared thoracic paravertebral block with the thoracic epidural combination of LA plus opioid (rather than LA alone), and showed mixed results for analgesia.65–67 Further evaluation of the risks and benefits of these techniques is warranted.
If thoracic epidural analgesia or paravertebral block are not feasible for any reason, including failure of the technique (although this is unusual), other regional techniques may be used. In this situation, intercostal nerve block with LA is recommended based on reduced pain and analgesic use compared with systemic analgesia in most procedure-specific studies. Comparisons with other regional analgesic techniques are limited, with especially few data concerning continuous intercostal nerve blocks,72 whereas this approach would appear logical considering the duration of postoperative pain after thoracotomy. Studies show a tendency towards greater pain and opioid consumption for intercostal nerve blocks compared with thoracic epidural analgesia.
Alternatively, if epidural analgesia or paravertebral block techniques cannot be used, a single, preoperative bolus of intrathecal opioid is recommended as part of a multi-analgesic regimen, in preference to IV patient-controlled analgesia opioids, based on a greater reduction in pain for up to 24 h. However, it is important to note that intrathecal administration of opioid as a single shot does not provide analgesia for more than 24 h, which is insufficient for most thoracotomy patients.
Interpleural LA is not recommended due to lack of efficacy compared with other regional techniques, and potential toxicity associated with high absorption of LA. Interpleural opioid is also not recommended because the only two studies show inconsistent results.
Methodological quality of the randomized trials in this systematic review varied. Allocation concealment, an important source of bias,97–99 was commonly unclear, while many studies were not double-blind. Quantitative analyses were limited as a result of heterogeneity in study design and outcome measures, and the number of subjects in the analyses was small. Although postoperative pain was the primary outcome of interest and a criterion for inclusion in the systematic review, it was not always the primary outcome of included studies, and measurements were often reported at limited time points, using different scales, and without statistical analyses. Not every study reported all outcomes of interest, such as pulmonary complications or pain on coughing/movement. Therefore, certain questions about the relative benefits of the different regional techniques remain unanswered until further large, well conducted trials are performed.
In conclusion, evidence supported the use of thoracic paravertebral block as an effective alternative to thoracic epidural LA alone, and showed that paravertebral block reduced the incidence of postoperative pulmonary complications compared with systemic analgesia. However, further studies are required to determine whether thoracic paravertebral block is equivalent to thoracic epidural combining LA plus opioid in terms of pain relief and morbidity. Apart from thoracic paravertebral block, all other regional analgesic techniques were inferior to thoracic epidural analgesia; in particular, interpleural techniques do not provide adequate analgesia. However, where thoracic epidural or paravertebral techniques are not possible or are contraindicated, then intercostal nerve block or preoperative intrathecal opioid are recommended.
The authors would like to thank Iradj Reza (PhD, Biomedical Information Scientist, Pfizer, Sandwich, UK) for his help and expertise in performing literature searches in Embase and Medline; and Caroline Sharp (MSc, Medical Projects Coordinator, Choice Pharma, Hitchin, UK), Christine Drewienkiewicz (BSc, Scientific Services Director, Choice Pharma) and James Pickford (BSc, Editorial Director, Choice Pharma) for editorial assistance.
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*Further details of treatment regimens, qualitative analyses, and figures showing additional quantitative analyses for pain scores, supplementary analgesic use and adverse effects are presented at www.postoppain.org.