Preventing Post-Thoracotomy Pain Syndrome

Authors


Abstract

This article provides a concise overview of post-thoracotomy pain syndrome, describes anesthetic and surgical factors that have been investigated to reduce the incidence of the syndrome, and explores the effectiveness of various treatments for this condition. Although some interventions (both procedural and pharmacologic) have been investigated in both preventing and treating post-thoracotomy pain syndrome, definitive studies are lacking and firm conclusions regarding the benefit of any intervention cannot be drawn. The problem is compounded further by our lack of understanding of the pathophysiologic mechanisms underlying the development of chronic pain after surgery. Going forward, it will be important to elucidate these mechanisms and conduct well-designed trials involving novel therapeutic agents for both prevention and treatment of post-thoracotomy pain syndrome. Mt Sinai J Med 79:133–139, 2012.© 2012 Mount Sinai School of Medicine

Thoracotomy is among the surgical procedures that have the greatest incidence of chronic postoperative pain and disability.1 Pain after thoracotomy may cause significant perioperative and long-term morbidity and is notable for its intensity and duration. In the immediate perioperative period, inadequately controlled pain can prevent patients from taking large-volume breaths, leading to pulmonary complications such as atelectasis and pneumonia.2,3 The International Association for the Study of Pain defines chronic post-thoracotomy pain as pain that recurs or persists along a thoracotomy scar >2 months after surgery.4 When such chronic pain occurs, it may be termed chronic post-thoracotomy pain (CPTP) or post-thoracotomy pain syndrome (PTPS). Post-thoracotomy pain syndrome is thought to be the result of injury to intercostal nerves, which transmit pain signals from the chest wall and costal pleura. These nerves may be injured during surgical incision, rib retraction, trocar placement, or suturing.5,6 Post-thoracotomy pain syndrome is typically described as aching or tenderness and is localized to the area of incision in approximately 82% of cases.7 Chronic post-thoracotomy pain remains a challenge for clinicians, as many treatment and prevention strategies have yielded disappointing results.

The International Association for the Study of Pain defines chronic post-thoracotomy pain as pain that recurs or persists along a thoracotomy scar >2 months after surgery. Such a post-thoracotomy pain syndrome is thought to be the result of injury to intercostal nerves, which transmit pain signals from the chest wall and costal pleura.

INCIDENCE

The incidence of chronic pain after thoracotomy is approximately 30%–50%.1,2,8 However, reported incidence varies widely, as investigators did not use a standardized set of criteria to classify subjects as having post-thoracotomy pain. For example, some studies considered subjects to have PTPS based upon whether pain was present or absent, whereas others required a certain level of pain intensity in order to designate a subject as having PTPS.9 Many of these investigations involved questionnaires and thus may have been significantly impacted by recall bias. Results from a fairly representative study indicated an overall incidence of 52% (32% mild, 16% moderate, and 3% severe chronic postoperative pain).10

The incidence of chronic pain after thoracotomy is approximately 30%–50%.

PREOPERATIVE FACTORS

Predicting which patients will develop PTPS is difficult. Risk factors for development of chronic pain after any type of surgery may include genetic susceptibility, age, sex, the presence of pain prior to surgery, and psychosocial factors.1 For example, older patients have reduced risk of chronic pain after hernia repair, whereas several studies have revealed that women have a higher risk of postoperative pain compared with men.11–14 However, no study has specifically investigated the impact of age and sex on the risk of development of PTPS. The degree to which genetics, preoperative pain, and psychosocial factors impact the risk of PTPS is unknown, and more studies are needed to clarify what role, if any, these factors play in the development of PTPS.9

INTRAOPERATIVE FACTORS

Surgical Factors

There are 4 basic types of surgical incisions that can be made during thoracotomy: (1) posterolateral, (2) muscle-sparing posterolateral (where the latissimus dorsi muscle is not divided), (3) axillary, or (4) anterior. It is unclear whether any approach is superior in preventing the development of PTPS. Two retrospective studies found no difference between the classic posterolateral approach and the muscle-sparing posterolateral approach.15,16 A subanalysis from a prospective study also found no difference in PTPS based on incision type.17 Finally, 2 additional retrospective studies found the anterior approach to result in less PTPS.18,19 However, because of a lack of prospective studies designed to specifically address the question of whether the type of surgical incision impacts the development of PTPS, no conclusions can be made about the potential benefit of one approach over others in reducing PTPS.9

Video-assisted thoracic surgery (VATS) was expected to reduce the incidence of PTPS; however, studies have yielded conflicting results. Two prospective trials found no differences in the incidence of PTPS when VATS was used compared with the classic posterolateral approach or the muscle-sparing posterolateral approach.20,21 One retrospective study concluded that VATS reduced PTPS when compared with a muscle-sparing incision.22

Other intraoperative surgical techniques that have been associated with reduced incidence of PTPS are harvesting an intercostal muscle flap, free dissection of intercostal nerves, and the use of intracostal sutures for closing the incision.9 A study by Cerfolio et al. revealed that harvesting an intercostal muscle flap before rib spreading reduces PTPS.23 In a prior study, Cerfolio et al. also demonstrated that the use of intracostal sutures (made by drilling holes in the rib) was superior to pericostal sutures (placing sutures around the rib) in reducing PTPS.24

Anesthetic Factors

It is important to note that the concept of preemptive analgesia, treatment that is initiated before in contrast to after the surgical procedure, has been largely replaced by preventive analgesia—the assumption that the only way to prevent central sensitization might be to completely block any pain and afferent signals from the surgical wound from the time of incision until final wound healing.25 Numerous anesthetic approaches have been investigated with the hope that implementation would reduce the incidence of PTPS. These techniques include thoracic epidural analgesia (TEA), paravertebral block and intercostal nerve block, cryoanalgesia, and various pharmacologic treatments.9

Thoracic Epidural Analgesia

Thoracic epidural anesthesia catheters are frequently placed in patients undergoing thoracotomy or VATS for acute postoperative pain control. Detailed below are 2 randomized controlled trials that found that TEA reduces PTPS, and a prospective randomized trial that found that the timing of TEA (preoperative or postoperative) did not influence the incidence of PTPS.17.26,27

Senturk et al. conducted a randomized, prospective study involving 69 patients, which compared the effects of 3 different analgesia techniques on post-thoracotomy pain: (1) TEA initiated preoperatively (group pre-TEA), (2) TEA initiated postoperatively (group post-TEA), and (3) intravenous patient-controlled analgesia (group IV-PCA). In group pre-TEA (n = 28), a 10-mL bolus of a solution of bupivacaine 0.1% + 0.1 mg/mL morphine in saline was administered at least 30 minutes before anesthetic induction, followed by a 7-mL/hour infusion of the same solution during the operation. Postoperative analgesia was maintained with epidural PCA with a concentration of bupivacaine of 0.1% + 0.05 mg/mL morphine.

In group post-TEA (n = 29), no epidural medication was administered until the postoperative period. Postoperative analgesic treatment was similar to group pre-TEA, except that the initial dose of 10 mL of the same solution was administered after extubation. In group IV-PCA (n = 28), subjects received morphine with a 5-mg initial dose, no basal infusion, and a 2-mg bolus dose with a 15-minute lockout time via IV-PCA. During the first 48 hours postoperatively, group pre-TEA had significantly less pain associated with movement or cough compared with the other 2 groups. At rest, patients in group pre-TEA reported having significantly lower pain scores during the first 12 hours compared with those in group post-TEA and during the first 48 hours compared with those in group IV-PCA. There were statistically significant differences in pain levels during rest between group post-TEA and group IV-PCA from 8 hours after surgery until the end of 48 hours, but no difference during cough or movement was recorded. In this study, 62% of the patients reported having pain after 6 months. Importantly, the incidence of pain in group IV-PCA was significantly more frequent than in group pre-TEA (P = 0.0233), but the difference between group post-TEA versus group pre-TEA and group IV-PCA was not significant. The severity of pain lasting >2 months after surgery was significantly diminished in the pre-TEA group. The authors concluded that TEA initiated preoperatively is a preferable method in preventing acute and chronic post-thoracotomy pain.26

Obata et al. conducted a double-blinded study in which 70 patients were assigned to randomly receive continuous epidural block with mepivacaine 1.5% either 20 minutes prior to surgical incision (Pre group) or at the completion of surgery (Post group). Indomethacin suppositories (50 mg) were also given to patients upon request as supplemental analgesics. A visual analog scale at rest was used to assess pain levels 4 hours after surgery and subsequently every 24 hours after surgery on postoperative days 1 through 7 and days 14–30. At 3 and 6 months after surgery, all patients were interviewed by telephone. The most severe pain was assessed using a modified numerical rating score. By visual analog scale, postoperative pain was less in the Pre group than in the Post group at 4 hours, 2 days, and 3 days postoperatively (P < 0.05). By numerical rating score, pain was less in the Pre group than in the Post group (P = 0.015) at 6 months. Also, the percentage of pain-free patients was higher in the Pre group than in the Post group at 3 months (P = 0.035) and 6 months (P = 0.0086) after surgery. The authors concluded that epidural blockade initiated prior to surgery may reduce the incidence of post-thoracotomy pain.27

In contrast to the above studies, which indicate a beneficial effect from TEA initiated preoperatively, one study concluded that preoperative initiation of TEA did not impact acute postoperative pain or chronic post-thoracotomy pain.17 Ochroch et al. randomized 157 patients undergoing elective major open thoracotomy (either classic posterolateral or a muscle-sparing incision) to receive thoracic epidural analgesia initiated prior to incision or at the time of rib approximation. Pain and activity scores were obtained at 4, 8, 12, 24, 36, and 48 weeks after surgery. Overall, there were no differences in pain scores between the control and treatment groups during hospitalization (P > 0.165) or after discharge (P > 0.098). The number of patients reporting pain 1 year after surgery (21.2%) was not significantly different from the number reporting preoperative pain (12.5%) (P = 0.122). During hospitalization, women reported greater pain than men. This is consistent with other studies indicating that women experience greater pain than men after surgery.12,13 Women continued to report greater discomfort than men after discharge (P < 0.016) but did not differ from men in their level of physical activity. The authors concluded that initiation of thoracic epidural analgesia prior to incision did not significantly impact pain or physical activity.17

Overall, it appears that TEA may be effective at reducing post-thoracotomy pain syndrome; however, the timing of initiation of TEA may not be of clinical significance.

Overall, it appears that thoracic epidural anesthesia may be effective at reducing post-thoracotomy pain syndrome; however, the timing of initiation of thoracic epidural anesthesia may not be of clinical significance.

Paravertebral Block

Paravertebral block is an alternative to TEA for controlling acute postoperative pain after thoracotomy. Although paravertebral blocks and TEA provide comparable pain relief, paravertebral blocks are associated with better postoperative respiratory function and less adverse effects on hemodynamics. Furthermore, paravertebral blocks are not associated with serious neurologic complications and may be particularly useful when epidural placement is contraindicated, as in patients with a preexisting coagulopathy.28,29 There is some evidence that use of paravertebral blocks may decrease the incidence of chronic pain after breast surgery, which is similar to PTPS due to the predominance of neuropathic features. However, the role of paravertebral blocks in preventing PTPS has not been investigated, but should be considered as a topic for future research.30,31

Intercostal Nerve Block

Neither intercostal nerve block nor injection of local anesthetics at the incision site has been shown to be effective in reducing PTPS.9 In one study, 30 subjects undergoing posterolateral thoracotomy were allocated randomly to receive 1 of 2 analgesic regimens: group Pre received IV morphine, diclofenac (intramuscular), and intercostal nerve blocks from T2 to T11 20 minutes before the operation and placebo injections after operation. Group Post received placebo injections before operation, and morphine IV, diclofenac (intramuscular), and intercostal nerve blocks from T2 to T11 at the end of surgery, before discontinuation of anesthesia. Visual analog pain scores, extent and duration of intercostal nerve block, analgesic consumption, and complications were assessed during the postoperative period by a single blinded observer. Subjects were followed up for a minimum of 12 months to determine the incidence of PTPS. During the first 48 hours after operation, there were lower pain scores in group Pre when taking a vital capacity breath, but there were no significant differences between the groups in any other measure. The authors concluded that the effects of preemptive analgesia given before surgery appeared to be relatively modest in terms of analgesia, analgesic consumption, and long-term outcome, and were of limited clinical significance.32

Cryoanalgesia

Cryoanalgesia has been shown in studies to be ineffective in preventing PTPS. Indeed, one study found that allodynia (perception of a nonpainful stimulus as being painful) increased with cryoanalgesia. Ju et al. studied 107 adult patients, allocated randomly to thoracic epidural bupivacaine and morphine or intercostal nerve cryoanalgesia. Acute pain scores and opioid-related side effects were evaluated for 3 postoperative days. Data including the incidence and severity of pain symptoms, and the presence of allodynia, were acquired on the first, third, sixth and 12 months postoperatively. There was no significant difference on numeric rating scales at rest or with movement between the 2 groups during the 3 postoperative days. The patient-satisfaction results were also similar between the groups. Both groups showed high incidence of chronic pain (42.1%–72.1%), without significance between the groups. More patients rated their chronic pain intensity as moderate or severe in the cryoanalgesia group and stated their pain interfered with daily life (P < 0.05). The authors concluded that cryoanalgesia may increase the incidence of neuropathic pain.33

Ketamine

Two trials concluded that ketamine is ineffective in preventing the development of PTPS.34,35 One study involved 86 patients who were randomized to receive intravenous ketamine, 1 mg/kg at induction followed by 1 mg/kg/hour during surgery, and finally 1 mg/kg as an infusion during the first 24 hours postoperatively. The patient's chest was examined 1–2 weeks, 6 weeks, and 4 months after surgery. At the last 2 observations, spontaneous pain score over a 1-week period (visual analog scale), neuropathic pain score, and intake of analgesics were assessed. Although ketamine improved immediate postsurgical pain, it failed to prevent the development of chronic pain measured in the long-term follow-up.36 Another trial investigated whether epidural ketamine would prevent development of PTPS. One hundred and thirty-three patients were randomized to preemptive TEA either with or without ketamine (group K: levobupivacaine, fentanyl, and ketamine, versus group KF: levobupivacaine and fentanyl). Pain at the thoracotomy scar site during rest and movement (coughing) was assessed at 2 weeks and 3 months after surgery using a visual analog scale. The incidence of allodynia and numbness was also evaluated. There was no difference in the incidence of chronic post-thoracotomy pain at 3 months between the 2 groups (67.7% in group K versus 75% in group KF). The incidences of allodynia or numbness were not different between the 2 groups. The authors found that the addition of preemptive low-dose epidural ketamine (1.2 mg/hour) to preemptive thoracic epidural analgesia did not have any beneficial effects in preventing chronic post-thoracotomy pain.35

Thus, although low-dose ketamine appears to be effective in decreasing postoperative pain, based on the above studies it lacks a more sustained benefit.

Cyclooxygenase-2 Inhibitors

Senard et al. conducted a prospective, randomized, double-blind, placebo-controlled study involving 40 patients undergoing thoracotomy to investigate the effect of oral celecoxib on postoperative analgesia combined with TEA. Epidural PCA (T4–T5) was used during the 48 hours after surgery. Patients were allocated to receive oral celecoxib or placebo from the evening before surgery until 48 hours after operation. Postoperative pain scores, respiratory function, and morbidity were compared between the 2 groups. Postoperative pain scores at rest (P = 0.026) and during coughing (P = 0.021) were lower and patient satisfaction was greater (P = 0.0033) in the celecoxib group. Consumption of the local anesthetic solution was comparable between groups. Postoperative restrictive pulmonary syndrome and morbidity were comparable between groups. The authors concluded celecoxib improves postoperative analgesia provided by TEA after thoracotomy.36 As there is no literature on the effect of nonsteroidal anti-inflammatory drugs or selective cyclooxygenase-2 inhibitors on CPTP, future studies on the subject are warranted.

Acetaminophen

Acetaminophen has been found to decrease post-thoracotomy ipsilateral shoulder pain when given preemptively and regularly during the first 48 hours postoperatively in patients who received TEA.37 Its ability to prevent chronic pain syndromes has not been studied and thus may be a topic of future research.

TREATMENT OF CHRONIC POST-THORACOTOMY PAIN

Because CPTP has a significant neuropathic component, systemic opioid therapy may not be effective for pain relief.38 Gabapentinoids, however, show promise as a therapy of CPTP. Solak et al. aimed to determine the safety and efficacy of gabapentin in comparison with naproxen sodium in patients with CPTP. The authors concluded that gabapentin is safe and effective in the treatment of CPTP with minimal side effects and a high patient compliance and suggested that the results be substantiated with multidisciplinary studies with larger sample sizes and longer follow-ups.39 Other medications such as pregabalin, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, lidocaine patches, and tramadol may be generally employed in the treatment of neuropathic pain.40 Use of ketamine for chronic neuropathic pain is largely anecdotal and requires further study.41

When medical therapy fails to provide relief, minimally invasive interventional techniques, such as intercostal nerve blocks and pulsed radiofrequency of the dorsal root ganglion, may be useful, but definitive studies are lacking.42,43 Although epidural injections may be helpful in alleviating certain types of thoracic pain, there are no studies assessing their role in the treatment of CPTP.44 Spinal cord and peripheral nerve stimulation may provide effective alternative options.45,46 Initially, trial leads are inserted and the patient is sent home with an external generator for a period of several days. During this time a range of complex stimulation programs is trialed, and if the patient reports significant pain relief, more permanent leads and a small implantable externally programmable generator are placed. This procedure is reversible; both the leads and the generator may be removed if pain relief becomes inadequate.

When medical therapy fails to provide relief, minimally invasive interventional techniques, such as intercostal nerve blocks and pulsed radiofrequency of the dorsal root ganglion, may be useful, but definitive studies are lacking.

CONCLUSION

Post-thoracotomy pain syndrome remains a poorly understood complication of thoracotomy. Although many studies have investigated methods to prevent PTPS, each one suffers from a variety of methodological flaws.9 Moreover, like other neuropathic pain syndromes, PTPS is difficult to manage with currently available pharmacologic agents, which further underscores the need to develop new pharmacologic agents and novel interventional approaches for treatment of neuropathic pain.

DISCLOSURES

Potential conflict of interest: Nothing to report.

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