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The State of the Art in Preventing Postthoracotomy Pain
STATE OF THE ART
The State of the Art in Preventing Postthoracotomy Pain Alan Romero, MD, Jose Enrique L. Garcia, MD, and Girish P. Joshi, MBBS, MD, FFARCSI Pain after thoracic surgery can be intense and prolonged. Inadequate pain management can have several detrimental effects, including increased postoperative morbidity and delayed recovery as well as occurrence of postthoracotomy syndrome. Therefore, establishing an adequate analgesic regimen for thoracic surgery is critical. Thoracic paravertebral block or thoracic epidural analgesia is recommended as the first-choice therapies for postthoracotomy analgesia. When these techniques are either contraindicated or not possible, intercostal analgesia or intrathecal opioids are recommended. These techniques should be combined with nonopioid analgesics, such as acetaminophen, nonsteroidal anti-inflammatory drugs, or cyclooxygenase-2-specific inhibitors, administered on a regular “round-the-clock” basis, with opioids used as “rescue” analgesics. Finally, the integration of multimodal analgesia techniques with multidisciplinary rehabilitation program can enhance recovery, reduce hospital stay, and facilitate early convalescence. Semin Thoracic Surg 25:116–124 I 2013 Elsevier Inc. All rights reserved. Keywords: thoracotomy, postoperative pain, regional analgesia, opioids, NSAIDs, COX-2 inhibitors INTRODUCTION Pain after thoracic surgery can be intense and prolonged.1,2 Inadequately treated postthoracotomy pain can have several negative consequences (Table 1). In recent years, persistent pain after surgery, also referred to as chronic postsurgical pain syndrome, has been recognized as a major factor delaying recovery and return to normal daily living.3,4 The reported incidence of persistent pain after thoracic surgery (postthoracotomy pain syndrome) has been reported in 20%-70% of patients.2,4,5 However, it is often underrecognized or undertreated. One of the factors that has been thought to influence postthoracotomy pain is the severity of pain in the immediate postoperative period. Thus, inadequately controlled pain can increase postoperative morbidity as well as reduce quality of life and
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas. Dr Joshi reports receiving consulting fees from Mallinkrodt and lecture fees from Pfizer, Cadence, and Pacira. Drs Garcia and Romero have no financial interests to disclose. Address reprint requests to Girish P. Joshi, MBBS, MD, FFARCSI, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9068. E-mail: [email protected]
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patient satisfaction.4 Nevertheless, inadequate postoperative pain relief remains a significant clinical problem. One of the reasons for suboptimal pain management may be related to inadequate or improper application of available analgesic therapies, possibly due to the significant amount of new and conflicting information that is increasingly available. A systematic review of published literature suggested that an optimal pain regimen would include regional anesthesia techniques such as thoracic epidural analgesia (TEA) or paravertebral block.1,6 If these techniques are contraindicated or not possible, a multimodal analgesia technique that uses a combination of analgesic therapies, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX)-2 selective inhibitors, and other analgesic adjuncts was recommended. The present review examines the current literature and provides an update regarding optimal approach for the management of postthoracotomy pain. Although there is a suggestion that the surgical approach may influence the incidence of postthoracotomy syndrome,2,4 it is not reviewed in this article. MULTIMODAL AND PREEMPTIVE ANALGESIA Multimodal analgesia involves the use of analgesics with different mechanisms of action to provide superior dynamic pain relief with reduced analgesic1043-0679/$-see front matter ª 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.semtcvs.2013.04.002
THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Table 1. Consequences of Inadequate Pain Management After Thoracic Surgery
Increased pulmonary complications Prolonged need for tracheal intubation and ventilation Prolonged intensive care unit stay Increased need for reintubation Prolonged hospital stay Chronic persistent postsurgical pain (postthoracotomy syndrome) Decreased social or emotional or mental health functioning Delayed return to activities of daily living Decreased patient satisfaction
related adverse effects. A rational combination of nonopioid analgesics has been shown to reduce opioid requirements as well as opioid-related adverse effects. The analgesic modalities available for postoperative pain management after thoracic surgery include regional or local analgesia techniques, such as epidural analgesia, paravertebral analgesia, intercostal nerve blocks (ICNB), and wound infiltration (Tables 2 and 3). In addition, acetaminophen, NSAIDs or COX-2-specific inhibitors, and analgesic adjuncts, such as steroids, ketamine, and gabapentinoids (eg, gabapentin and pregabalin), have been evaluated (Table 4).2,7 An ideal analgesic combination would reduce the intensity of movement-evoked pain (eg, during coughing and ambulation), while avoiding analgesic-related adverse effects, and improve postoperative outcome. The choice of analgesic combination is generally based on the type, efficacy, and side effect profile of the analgesic modality for a specific surgical procedure.8 For example, patients undergoing thoracotomy require more aggressive approach (eg, neuraxial analgesia) as compared to those undergoing thoracoscopic surgery. The concept of preemptive analgesia (ie, analgesic intervention made before surgical insult) to prevent establishment of peripheral and central sensitization and thus amplification and prolongation of pain has been overwhelmingly demonstrated in animal models. However, clinical studies have provided conflicting results. The reasons for the failure of clinical studies to show benefits may be due to the use of unimodal, rather than multimodal, analgesia techniques and short duration of analgesia. While we wait for further evidence, analgesics could be administered either preoperatively or intraoperatively such that their peak effect occurs just prior to emergence from anesthesia. REGIONAL ANALGESIA TECHNIQUES TEA TEA has been shown to provide excellent dynamic pain relief, as well as prevent postoperative
Table 2. Analgesic Options for Prevention of Postthoracotomy Pain Regional Analgesia Techniques
Thoracic epidural Paravertebral block Intrathecal opioids Intercostal nerve blocks Intrapleural analgesia Wound infiltration Systemic Analgesia
Acetaminophen Nonsteroidal anti-inflammatory drugs Cyclooxygenase (COX)-2-specific inhibitors Opioids Analgesic Adjuncts
Steroids (dexamethasone) Ketamine Gabapentinoids (gabapentin and pregabalin)
pulmonary complications after thoracic surgery, and enhance rehabilitation. Therefore, it has long been considered the “gold standard” for pain control in patients undergoing thoracic procedures. Although the optimal timing for initiation of TEA (ie, intraoperative vs postoperative) remains controversial, its use for a minimum of 48 hours is required to demonstrate improved outcomes postthoracotomy.1 A recent randomized trial found improved pain scores at all measured time points as well as better mean physical and mental quality of life measures with TEA compared with intravenous (IV) patientcontrolled analgesia with morphine.9 The authors hypothesized that the differences in quality of life measures between the 2 groups were not only secondary to superior postoperative pain relief but also due to reduced opioid-related adverse effects such as nausea, vomiting, and sleep disturbances.9 A recent study comparing the analgesic efficacy of combining celecoxib with TEA alone found that
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Table 3. Regional Analgesia Techniques for Thoracic Surgery Regional Anesthesia Techniques Thoracic paravertebral analgesia
Benefits
Risks
Superior dynamic analgesia during coughing and physical therapy
Epidural spread of local anesthetic with associated risks, vascular injury, and pleural injury Potential for catastrophic neurologic complications is remote
Recommended
Improved postoperative outcome Equally effective as TEA Trend toward lower incidence of major complications compared with TEA and lower block failure rate Limited value with singleshot injection
Recommendations
Thoracic epidural analgesia (TEA)
Superior analgesia during coughing and physical therapy, and improved postoperative outcome
High (15%) failure rate, complicates postoperative anticoagulation, hypotension, nausea, urinary retention, pruritus, accidental intrathecal spread, epidural hematoma, and epidural abscess
Recommended
Intrathecal opioid analgesia
Better static and dynamic pain scores compared with systemic opioid analgesia specifically in first 24 h postoperatively
Risk of respiratory depression, pruritus, urinary retention, nausea, and vomiting
Recommended, if paravertebral block or TEA is contraindicated or not possible
Intercostal analgesia
Simple and easy to perform, superior pain scores, reduced opioid requirements, and improved postoperative outcome
Systemic local toxicity, better pain scores with continuous catheter, or multiple injections
Recommended in combination with nonopioid analgesics, such as acetaminophen and NSAIDs or COX-2specific inhibitors, if paravertebral block or TEA is contraindicated or not possible
Interpleural analgesia
Easy to perform but not efficacious
Potential of local anesthetic toxicity
Not Recommended
Intercostal nerve cryoanalgesia
Effective in perioperative period in improving pain scores compared with placebo
Implicated in increasing incidence of chronic pain
Not Recommended
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Table 4. Nonopioid Analgesics Systemic Analgesics
Benefits
Risks
Recommendations
Acetaminophen
Safe, effective analgesic and antipyretic Reduces pain scores and opioid requirements No increased incidence in hemorrhage, gastric ulceration, cardiovascular, and renal adverse effects Has “ceiling effect”
Liver toxicity
Recommended in combination with other analgesics
Nonsteroidal antiinflammatory drugs (NSAIDs)
Improves pain relief Reduces opioid consumption by 30% and decreases opioidrelated adverse effects
Impaired coagulation, gastric irritation, renal dysfunction, and cardiovascular adverse effects
Recommended in combination with other analgesics
Cyclooxygenase (COX)-2 Inhibitors
Improves pain scores, decreases opioid consumption, and reduces opioid-related adverse effects Similar efficacy as NSAIDs No effects on platelet function and perioperative bleeding
Potential gastric irritation, renal dysfunction, and cardiovascular adverse effects
Recommended in combination with other analgesics
Glucocorticoids (dexamethasone)
Reduces inflammation, improves pain relief, prolongs time to first analgesic, and modest reduction in opioid requirements
Increase blood glucose levels up to 24 h, but may not be clinically relevant
Recommended as an adjunct
Ketamine
Analgesic properties without respiratory depressive effects, reduces pain scores, and opioid consumption, and prolongs time to first analgesic Optimal dose and duration of administration remain controversial
Sympathomimetic and neurocognitive side effects
Not recommended for routine use
Gabapentinoids (gabapentin and pregabalin)
Reduced pain scores and opioid requirements Optimal dose and duration of administration remain controversial
Sedation, dizziness, and visual disturbances
Not recommended for routine use
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN the combination resulted in lower pain scores at rest, coughing, and mobilization during the first 48 hours postoperative period without increasing perioperative bleeding.10 They also noted that the patient satisfaction scores were greater in the combination group.10 Interestingly, it appears that the relative benefits of TEA in reducing postoperative pulmonary complications have decreased over the last few decades, which is probably due to improved surgical techniques, prophylactic antibiotics, improved postoperative care (eg, avoidance of nasogastric tubes), improved pulmonary physiotherapy, and early mobilization.11 Thus, although the analgesic benefits of TEA have been reported to be favorable in patients with chronic obstructive pulmonary disease,12 its routine use is being increasingly questioned.13-15 Of note, TEA is associated with several potential adverse effects; however, their overall incidence is low (Table 3).
Paravertebral Analgesia Paravertebral block can be performed by administration of local anesthetic in the paravertebral space through a percutaneous posterior approach using either a loss of resistance or ultrasound-guided technique. Alternatively, it can be placed under direct visualization by the surgeon, at the end of surgery.1 Several recent systematic reviews and metaanalysis have found no difference in analgesic efficacy and the need for supplemental opioid requirements between paravertebral analgesia and TEA in patients undergoing thoracic surgery.1,16 In addition, postoperative pulmonary function and incidence of pulmonary complications were also similar between the 2 techniques. Use of paravertebral analgesia avoids the potential complications associated with TEA.1,16,17 A recent observational trial in patients undergoing pneumonectomy explored the effects of paravertebral block and TEA on major postoperative complications, including hypotension requiring inotrope therapy, arrhythmias requiring antiarrhythmic therapy, respiratory complications requiring ventilator support, and the need for further surgery.17 This study found that patients who received TEA had a higher incidence of major complications compared with those patients who received thoracic paravertebral analgesia. Also, occurrence of accidental dural puncture and postdural puncture headache is unlikely with paravertebral block. Furthermore, the potential for catastrophic neurologic injuries resulting from epidural hematoma and abscess is remote with paravertebral analgesia.
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One of the concerns with paravertebral analgesia is that the local anesthetic may spread from the paravertebral space to the epidural space, thus causing the potential complications of epidural analgesia. There appears to be an epidural spread in up to 70% of patients receiving paravertebral analgesia, which is influenced by the technique (eg, ultrasound technique appears to increase the risk of epidural spread) and volume of local anesthetic (eg, single large-volume injection technique is associated with higher spread as opposed to multiple small volumes or continuous infusion) as well as practitioner experience and anatomical deformity, which can influence the local anesthetic spread.18 Nevertheless, most injections resulting in epidural spread have limited side effects, such as transient hypotension and lower limb weakness. However, if the local anesthetic is misplaced in the intrathecal space, total spinal anesthesia requiring tracheal intubation and hemodynamic support may result.18 Other potential complications associated with paravertebral block include vascular and pleural injury, which can increase up to 8-fold with bilateral paravertebral blocks.18 Although the paravertebral space is highly vascular, the likelihood of hematoma formation resulting in significant morbidity is very rare. The block failure rate with thoracic paravertebral blocks is reported to be lower than that with TEA. Because of equivalent analgesic efficacy and superior side effect profile compared with TEA, paravertebral analgesia has recently had a resurgence and is currently recommended over TEA.1 Of note, the use of continuous local anesthetic infusion is preferred, because of superiority over a single injection technique. There appears to be no difference in the choice of local anesthetics, as continuous infusion of bupivacaine, ropivacaine, and lidocaine is equally efficacious. However, longer-acting local anesthetics are recommended for single injection techniques. The addition of fentanyl in combination with local anesthetic in the infusion has been shown to provide similar pain relief compared with local anesthetic alone. Also, the addition of clonidine to local anesthetic has provided contradictory evidence with respect to analgesia and has been reported to increase sedation. Thus, the addition of adjuncts, such as fentanyl and clonidine, to local anesthetic solution is not recommended.
Intrathecal Opioid Analgesia Intrathecal opioid analgesia is an established pain treatment modality in postthoracotomy pain.19 A
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN recent meta-analysis ascertained the efficacy of intrathecal opioids in major surgery, which included cardiothoracic and major abdominal surgery.19 A single dose of intrathecal morphine was able to decrease 24-hour static and movement-related pain intensity scores.19 The risk of respiratory depression from intrathecal morphine ranges from 1.2%-6.7% and can result from even a small dosage such as 200300 mg of morphine.19 Other side effects include pruritus, urinary retention, nausea, and vomiting. The addition of clonidine to intrathecal morphine is not recommended because of minimal benefits and high incidence of hypotension.20 A recent study comparing TEA with paravertebral block combined with intrathecal morphine found that both the techniques provided similar pain relief and thus could be used alternatively.21 However, the need for adding intrathecal morphine with paravertebral block is questionable. Nevertheless, intrathecal opioids can be considered as a part of a multimodal analgesic regimen when regional alternatives such as TEA or paravertebral analgesia are not possible or contraindicated.1
Intercostal Analgesia ICNB have long been used as an analgesic technique for thoracic surgery. These blocks are easier and faster to perform. They can be accomplished by placement of a catheter in the intercostal space at the end of the surgery under direct visualization by the surgeon. A systematic review found reduced postoperative pain scores with ICNB, compared with placebo,1 particularly administered as repeat blocks or continuous infusion. Studies comparing ICNB with TEA have reported conflicting results with respect to pain relief and opioid requirements as well as postoperative pulmonary function.22 However, TEA was associated with a higher incidence of pruritus and need for a urinary catheter.22 Overall, ICNB are an alternative to TEA or paravertebral blocks,1 particularly when those techniques are contraindicated or not possible. Interpleural Analgesia Interpleural analgesia is performed by injecting local anesthetic in the pleural space between the parietal and visceral pleura with the proposed mechanism of action appearing to be diffusion of local anesthetic across the parietal pleura.1 However, this technique is not recommended because of the lack of efficacy compared with other regional techniques, as well as potential toxicity associated with absorption of local anesthetic.1
Intercostal Nerve Cryoanalgesia Cryoanalgesia involves freezing the intercostal nerves resulting in axonal disintegration and degeneration of the myelin sheaths which leads to long-lasting neurolysis and postoperative pain relief.23 Previous studies have reported beneficial analgesic effects of intercostal nerve cryoanalgesia. However, several more recent studies have implicated cryoanalgesia in increasing the incidence of chronic pain and paresthesia.23,24 Thus, intercostal nerve cryoanalgesia is not considered a suitable technique for pain management after thoracic surgery.1 SYSTEMIC ANALGESIC TECHNIQUES Opioid Analgesia Systemic opioids have long been a major component of perioperative pain management. However, there is increased emphasis in reducing the opioid dose owing to concerns of opioid-related adverse events, including hypoventilation, sedation, constipation, nausea, vomiting, pruritus, and interrupted sleep patterns, all of which may contribute to a delayed recovery.1 Thus, it is recommended that nonopioid analgesic techniques should be the first line of therapy with opioids reserved for more severe pain that is not adequately controlled with nonopioids. Acetaminophen Acetaminophen has established itself as a safe and effective analgesic and antipyretic. Although the mechanism of action of acetaminophen remains unclear, its site of action is thought be central in origin (ie, the spinal cord and brain). Acetaminophen is devoid of some of the adverse effects of NSAIDs, such as gastrointestinal ulceration and hemorrhage, cardiorenal adverse effects, and impaired platelet aggregation. However, there is a concern of liver toxicity, particularly in patients with compromised hepatic function, severe alcoholism, cirrhosis, or hepatitis. Importantly, these patients should be warned that commonly used opioid combinations might contain acetaminophen. The Food and Drug Administration in the United States recently approved an intravenous formulation of acetaminophen, although it has been available in Europe for over a decade. Intraoperative administration of IV acetaminophen has been shown to reduce postoperative pain scores and opioid requirements, and has been advocated as a part of a multimodal analgesia technique.25 In intensive care unit patients, IV acetaminophen significantly reduced the time to tracheal extubation with
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Thoracic Paravertebral Analgesia (continued for 48-72 h) Or Thoracic Epidural Analgesia (continued for 48-72 h)
If contraindicated or not possible
Intercostal Nerve Block (continuous infusion for 48-72 h) + Wound infiltration Or Intrathecal Morphine
Combined with
Acetaminophen + NSAIDs or COX-2 specific inhibitors + Opioid (IV-PCA) for “rescue” Consider adding
Dexamethasone as analgesic adjunct
Figure 1. Recommendations for prevention of postthoracotomy pain. IV-PCA, intravenous patient-controlled analgesia. (Color version of figure is available online at http://www.seminthorcardiovascsurg.com.)
superior pain scores compared with placebo.26 Similar to NSAIDs and COX-2-specific inhibitors, acetaminophen also exhibits an analgesic “ceiling” effect.27 The combination of acetaminophen with NSAIDs or COX-2-specific inhibitors has been shown to provide superior analgesia compared with either drug alone.28,29
NSAIDs The mechanism of analgesic effects of NSAIDs is through inhibition of the COX-2 enzyme. The NSAIDs have been shown to reduce postoperative pain as well as opioid requirements and are recommended as an important component of the multimodal analgesia technique. In patients undergoing thoracic surgery, NSAIDs have been shown to reduce opioid consumption by approximately 30%.1,28,29 With the introduction of parenteral preparations of NSAIDs (eg, ketorolac and ibuprofen), this class of drugs has become more popular in the management of postoperative pain. Potential side effects of NSAIDs include impaired coagulation (and increased perioperative bleeding), gastric irritation (particularly when these drugs are administered in fasting patients), and renal dysfunction. Thus, NSAIDs should not be used in patients with preexisting coagulation defects or those undergoing surgical procedures with potential for
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significant bleeding. In addition, NSAIDs should be avoided in patients with preexisting renal dysfunction, hypovolemia, cardiac failure, sepsis, or endstage liver disease.
COX-2-Specific Inhibitors COX-2-specific inhibitors selectively inhibit the COX-2 enzyme and spare the COX-1 enzyme. Thus, COX-2-specific inhibitors lack the antiplatelet effects of the traditional NSAIDs. However, in the perioperative period, the cardiovascular and renal side effect profile of COX-2-specific inhibitors seems to be equivalent to that of nonselective NSAIDs. The analgesic efficacy of COX-2-specific inhibitors is similar to that of the traditional NSAIDs. Thus, the COX-2-specific inhibitors improve pain scores, decrease opioid consumption, and reduce opioidrelated side effects. Because the COX-2-specific inhibitors do not have any antiplatelet effects, there is no concern of increased perioperative bleeding with this group of drugs, and they can be administered preoperatively.1 ANALGESIC ADJUNCTS Glucocorticoids Glucocorticoids have been used to reduce inflammation and tissue damage, which can reduce pain.
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Multiple studies have noted that single dose of dexamethasone reduced postoperative pain and prolonged time to first analgesic request.30,31 Interestingly, the reduction in opioid consumption at 2 and 24 hours was modest. Although the optimal dosage remains debatable, most studies have used doses of 4-8 mg, IV given either preoperatively or intraoperatively. A single dose of dexamethasone has not been shown to increase the incidence of surgical site infections, but it may increase blood glucose levels lasting for up to 24 hours postoperatively. The clinical significance of this increase in blood glucose levels is not known. Ketamine Ketamine is an N-methyl-D-aspartate antagonist that has analgesic properties without respiratory depressive effects. Several systematic reviews have found that low-dose ketamine reduces postoperative pain scores and opioid consumption as well as delayed time to first opioid administration. A recent systematic review revealed that ketamine provided significant analgesic benefits in painful procedures, including thoracic, upper abdominal, and major orthopedic surgeries.32 Interestingly, the analgesic effects of ketamine were independent of the type of intraoperative opioid administered, timing of ketamine administration, and the ketamine dose. The authors also concluded that the opioid-sparing effects of ketamine reduced the incidence of nausea and vomiting and was associated with an increase in the incidence of neuropsychiatric disturbances.32 Thus, intravenous ketamine may play a role as an adjunct to other nonopioid analgesics, but the optimal dose and duration of administration remain controversial. Similarly, the role of ketamine in reducing postthoracotomy syndrome remains controversial. A recent study found that although ketamine reduced pain in the immediate postoperative period, it did not reduce the incidence of pain at 3 and 6 months after surgery.33 Gabapentoids Both gabapentin and pregabalin are structural analogs of gamma-aminobutyric acid and have the same mechanism of action. They are thought to work through modulating the α-2-δ subunit of voltagegated calcium channels in the dorsal horns of the spinal cord. These drugs are commonly used for the management of neuropathic pain. However, they have also been extensively studied in the perioperative setting. Because persistent postsurgical pain is thought to be neuropathic in nature, theoretically gabapentinoids may be of benefit in its prevention.
Several placebo-controlled randomized trials have reported improved pain scores and reduced opioid requirements with both gabapentin and pregabalin.34,35 A recent systematic review found that perioperative pregabalin reduced opioid consumption and opioid-related adverse effects after surgery.35 However, the incidence of visual disturbances was high. Other side effects of this group of drugs include dizziness and drowsiness. The optimal dose and duration of administration of these drugs remain unknown. These drugs have also been shown to be effective in the treatment of postthoracotomy pain syndrome; however, it remains unclear whether they can prevent this syndrome.
SUMMARY The benefits of optimal pain management are well recognized. These include enhanced recovery and reduced intensive care unit and hospital length of stay. Thus, adequate pain control would improve health care resource utilization and reduce health care costs.2 Based on the current evidence, thoracic paravertebral block and TEA are recommended as the first-choice therapies for postthoracotomy analgesia (Fig. 1). Given the lack of superiority of TEA over paravertebral analgesic and the potential risk of adverse effects of TEA, paravertebral analgesia may offer some advantages. One issue that remains unresolved is the efficacy of neuraxial analgesia techniques (ie, epidural and paravertebral analgesic) in reducing postthoracotomy pain syndrome. When either TEA or paravertebral analgesia is contraindicated or not possible, intercostal analgesia or intrathecal opioids are recommended. These techniques should be combined with nonopioid analgesics, such as acetaminophen, NSAIDs or COX-2-specific inhibitors, and dexamethasone, assuming there are no contraindications, with IV patient-controlled analgesia opioids for rescue. Furthermore, it is imperative that these nonopioid analgesics are administered on a regular “roundthe-clock” basis with opioids used as “rescue” analgesics. The role of ketamine and gabapentinoids remains controversial, and further studies are necessary before these drugs can be recommended for routine use. Nevertheless, these drugs may be beneficial for the patient who is opioid tolerant and those at high risk of persistent postsurgical pain. Finally, the integration of multimodal analgesia techniques with multidisciplinary rehabilitation program can enhance recovery, reduce hospital stay, and facilitate early convalescence.2
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN 1. Joshi GP, Bonnet F, Shah R, et al: A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia. Anesth Analg 107:1026–1040, 2008 2. Jones NL, Edmonds L, Ghosh S, et al: A review of enhanced recovery for thoracic anaesthesia and surgery. Anaesthesia 68: 179–189, 2013 3. Joshi GP, Ogunnaike B: Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin N Am 23:21–36, 2005 4. Kinney MA, Hooten WM, Cassivi SD, et al: Chronic postthoracotomy pain and healthrelated quality of life. Ann Thorac Surg 93: 1242–1247, 2012 5. Kehlet H, Hensen TS, Woolf CJ: Persistent postsurgical pain: Risk factors and prevention. Lancet 367:1618–1625, 2006 6. PROSPECT: Procedure-specific postoperative pain management Available at: www.postop pain.org. 7. Joshi GP: Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin N Am 23:185–202, 2005 8. Kehlet H, Wilkinson RC, Fischer HB, et al: PROSPECT: Evidence-based, procedurespecific postoperative pain management. Best Prac Res Clin Anesthesiol 21:149–159, 2007 9. Ali M, Winter DC, Hanly AM, et al: Prospective, randomized, controlled trial of thoracic epidural or patient-controlled opiate analgesia on perioperative quality of life. Br J Anaesth 104:292–297, 2010 10. Senard M, Deflandre EP, Ledoux D, et al: Effect of celecoxib combined with thoracic epidural analgesia on pain after thoracotomy. Br J Anaesth 105:196–200, 2010 11. Popping DM, Elia N, Marret E, et al: Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: A meta-analysis. Arch Surg 143: 990–999, 2008 12. Van Lier F, Van Der Geest PJ, Hoeks SE, et al: Epidural analgesia is associated with improved health outcomes of surgical patients with chronic obstructive pulmonary disease. Anesthesiology 115:315–321, 2011 13. Low J, Johnston N, Morris C: Epidural analgesia: First do no harm. Anaesthesia 63:1–3, 2008
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14. Freise H, Van Aken HK: Risks and benefits of thoracic epidural anaesthesia. Br J Anaesth 107: 859–868, 2011 15. Rawal N: Epidural technique for postoperative pain gold standard no more? Reg Anesth Pain Med 37:310–317, 2012 16. Kotze A, Scally A, Howell S: Efficacy and safety of different techniques of paravertebral block for analgesia after thoracotomy: A systematic review and metaregression. Br J Anaesth 103: 626–636, 2009 17. Powell ES, Cook D, Pearce AC, et al: A prospective, multicenter, observational cohort study of analgesia and outcome after pneumonectomy. Br J Anaesth 106:364–370, 2011 18. Chelly JE: Paravertebral blocks. Anesthesiol Clin 30:75–90, 2012 19. Meylan N, Elia N, Lysakowski C, et al: Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: Meta-analysis of randomized trials. Br J Anaesth 102:156–167, 2009 20. Engelman E, Marsala C: Efficacy of adding clonidine to intrathecal morphine in acute postoperative pain: Meta-analysis. Br J Anaesth 110:21–27, 2013 21. Dango S, Harris S, Offner K, et al: Combined paravertebral and intrathecal vs thoracic epidural analgesia for post-thoracotomy pain relief. Br J Anaesth 110:443–449, 2013 22. Meierhenrich R, Hock D, Kuhn S, et al: Analgesia and pulmonary function after lung surgery: Is a single intercostal nerve block plus patient-controlled intravenous morphine as effective as patient-controlled epidural anesthesia? A randomized non-inferiority clinical trial. Br J Anaesth 106:580–589, 2011 23. Ju H, Feng Y, Yang B, et al: Comparison of epidural analgesia and intercostal nerve cryoanalgesia for post-thoracotomy pain control. Eur J Pain 12:378–384, 2008 24. Mustola ST, Lempinen J, Saimanen E, et al: Efficacy of thoracic epidural analgesia with or without intercostal nerve cryoanalgesia for postthoracotomy pain. Ann Thorac Surg 91: 869–873, 2011 25. McNicol ED, Tzortzopoulou A, Cepeda MS, et al: Single-dose intravenous paracetamol or propacetamol for prevention or treatment of
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postoperative pain: A systematic review and meta-analysis. Br J Anaesth 106:764–775, 2011 Memis D, Inal MT, Kavalci G, et al: Intravenous paracetamol reduced the use of opioids, extubation time, and opioid-related adverse effects after major surgery in intensive care unit. J Crit Care 25:458–462, 2010 Hahn TW, Mogensen T, Lund LS, et al: Analgesic effect of i.v. paracetamol: Possible ceiling effect of paracetamol in postoperative pain. Acta Anaesthesiol Scand 47:138–145, 2003 Ong CK, Seymour RA, Lirk P, et al: Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: A qualitative systematic review of analgesic efficacy for acute postoperative pain. Anesth Analg 110: 1170–1179, 2010 Maund E, McDaid C, Rice S, et al: Paracetamol and selective and non-selective non-steroidal anti-inflammatory drugs for the reduction in morphine-related side-effects after major surgery: A systematic review. Br J Anaesth 106: 292–297, 2011 De Oliveira GS, Almeida MD, Benzon HT, et al: Perioperative single dose systemic dexamethasone for postoperative pain: A meta-analysis of randomized controlled trials. Anesthesiology 115:575–588, 2011 Waldron NH, Jones CA, Gan TJ, et al: Impact of perioperative dexamethasone on postoperative analgesia and side-effects: Systematic review and meta-analysis. Br J Anaesth 110:191–200, 2013 Laskowski K, Stirling A, McKay WP, et al: A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth 58: 911–923, 2011 Mendola C, Cammaroto G, Netto R, et al: S (þ)-ketamine for control of perioperative pain and prevention of post thoracotomy pain syndrome: A randomized, double-blind study. Minerva Anestesiol 78:757–766, 2012 Ho KY, Gan TJ, Habib AS: Gabapentin and postoperative pain—A systematic review of randomized controlled trials. Pain 126: 91–101, 2006 Zhang J, Ho KY, Wang Y: Efficacy of pregabalin in acute postoperative pain: A meta-analysis. Br J Anaesth 106:454–462, 2011
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The State of the Art in Preventing Postthoracotomy Pain Alan Romero, MD, Jose Enrique L. Garcia, MD, and Girish P. Joshi, MBBS, MD, FFARCSI Pain after thoracic surgery can be intense and prolonged. Inadequate pain management can have several detrimental effects, including increased postoperative morbidity and delayed recovery as well as occurrence of postthoracotomy syndrome. Therefore, establishing an adequate analgesic regimen for thoracic surgery is critical. Thoracic paravertebral block or thoracic epidural analgesia is recommended as the first-choice therapies for postthoracotomy analgesia. When these techniques are either contraindicated or not possible, intercostal analgesia or intrathecal opioids are recommended. These techniques should be combined with nonopioid analgesics, such as acetaminophen, nonsteroidal anti-inflammatory drugs, or cyclooxygenase-2-specific inhibitors, administered on a regular “round-the-clock” basis, with opioids used as “rescue” analgesics. Finally, the integration of multimodal analgesia techniques with multidisciplinary rehabilitation program can enhance recovery, reduce hospital stay, and facilitate early convalescence. Semin Thoracic Surg 25:116–124 I 2013 Elsevier Inc. All rights reserved. Keywords: thoracotomy, postoperative pain, regional analgesia, opioids, NSAIDs, COX-2 inhibitors INTRODUCTION Pain after thoracic surgery can be intense and prolonged.1,2 Inadequately treated postthoracotomy pain can have several negative consequences (Table 1). In recent years, persistent pain after surgery, also referred to as chronic postsurgical pain syndrome, has been recognized as a major factor delaying recovery and return to normal daily living.3,4 The reported incidence of persistent pain after thoracic surgery (postthoracotomy pain syndrome) has been reported in 20%-70% of patients.2,4,5 However, it is often underrecognized or undertreated. One of the factors that has been thought to influence postthoracotomy pain is the severity of pain in the immediate postoperative period. Thus, inadequately controlled pain can increase postoperative morbidity as well as reduce quality of life and
Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas. Dr Joshi reports receiving consulting fees from Mallinkrodt and lecture fees from Pfizer, Cadence, and Pacira. Drs Garcia and Romero have no financial interests to disclose. Address reprint requests to Girish P. Joshi, MBBS, MD, FFARCSI, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-9068. E-mail: [email protected]
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patient satisfaction.4 Nevertheless, inadequate postoperative pain relief remains a significant clinical problem. One of the reasons for suboptimal pain management may be related to inadequate or improper application of available analgesic therapies, possibly due to the significant amount of new and conflicting information that is increasingly available. A systematic review of published literature suggested that an optimal pain regimen would include regional anesthesia techniques such as thoracic epidural analgesia (TEA) or paravertebral block.1,6 If these techniques are contraindicated or not possible, a multimodal analgesia technique that uses a combination of analgesic therapies, such as acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase (COX)-2 selective inhibitors, and other analgesic adjuncts was recommended. The present review examines the current literature and provides an update regarding optimal approach for the management of postthoracotomy pain. Although there is a suggestion that the surgical approach may influence the incidence of postthoracotomy syndrome,2,4 it is not reviewed in this article. MULTIMODAL AND PREEMPTIVE ANALGESIA Multimodal analgesia involves the use of analgesics with different mechanisms of action to provide superior dynamic pain relief with reduced analgesic1043-0679/$-see front matter ª 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1053/j.semtcvs.2013.04.002
THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Table 1. Consequences of Inadequate Pain Management After Thoracic Surgery
Increased pulmonary complications Prolonged need for tracheal intubation and ventilation Prolonged intensive care unit stay Increased need for reintubation Prolonged hospital stay Chronic persistent postsurgical pain (postthoracotomy syndrome) Decreased social or emotional or mental health functioning Delayed return to activities of daily living Decreased patient satisfaction
related adverse effects. A rational combination of nonopioid analgesics has been shown to reduce opioid requirements as well as opioid-related adverse effects. The analgesic modalities available for postoperative pain management after thoracic surgery include regional or local analgesia techniques, such as epidural analgesia, paravertebral analgesia, intercostal nerve blocks (ICNB), and wound infiltration (Tables 2 and 3). In addition, acetaminophen, NSAIDs or COX-2-specific inhibitors, and analgesic adjuncts, such as steroids, ketamine, and gabapentinoids (eg, gabapentin and pregabalin), have been evaluated (Table 4).2,7 An ideal analgesic combination would reduce the intensity of movement-evoked pain (eg, during coughing and ambulation), while avoiding analgesic-related adverse effects, and improve postoperative outcome. The choice of analgesic combination is generally based on the type, efficacy, and side effect profile of the analgesic modality for a specific surgical procedure.8 For example, patients undergoing thoracotomy require more aggressive approach (eg, neuraxial analgesia) as compared to those undergoing thoracoscopic surgery. The concept of preemptive analgesia (ie, analgesic intervention made before surgical insult) to prevent establishment of peripheral and central sensitization and thus amplification and prolongation of pain has been overwhelmingly demonstrated in animal models. However, clinical studies have provided conflicting results. The reasons for the failure of clinical studies to show benefits may be due to the use of unimodal, rather than multimodal, analgesia techniques and short duration of analgesia. While we wait for further evidence, analgesics could be administered either preoperatively or intraoperatively such that their peak effect occurs just prior to emergence from anesthesia. REGIONAL ANALGESIA TECHNIQUES TEA TEA has been shown to provide excellent dynamic pain relief, as well as prevent postoperative
Table 2. Analgesic Options for Prevention of Postthoracotomy Pain Regional Analgesia Techniques
Thoracic epidural Paravertebral block Intrathecal opioids Intercostal nerve blocks Intrapleural analgesia Wound infiltration Systemic Analgesia
Acetaminophen Nonsteroidal anti-inflammatory drugs Cyclooxygenase (COX)-2-specific inhibitors Opioids Analgesic Adjuncts
Steroids (dexamethasone) Ketamine Gabapentinoids (gabapentin and pregabalin)
pulmonary complications after thoracic surgery, and enhance rehabilitation. Therefore, it has long been considered the “gold standard” for pain control in patients undergoing thoracic procedures. Although the optimal timing for initiation of TEA (ie, intraoperative vs postoperative) remains controversial, its use for a minimum of 48 hours is required to demonstrate improved outcomes postthoracotomy.1 A recent randomized trial found improved pain scores at all measured time points as well as better mean physical and mental quality of life measures with TEA compared with intravenous (IV) patientcontrolled analgesia with morphine.9 The authors hypothesized that the differences in quality of life measures between the 2 groups were not only secondary to superior postoperative pain relief but also due to reduced opioid-related adverse effects such as nausea, vomiting, and sleep disturbances.9 A recent study comparing the analgesic efficacy of combining celecoxib with TEA alone found that
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Table 3. Regional Analgesia Techniques for Thoracic Surgery Regional Anesthesia Techniques Thoracic paravertebral analgesia
Benefits
Risks
Superior dynamic analgesia during coughing and physical therapy
Epidural spread of local anesthetic with associated risks, vascular injury, and pleural injury Potential for catastrophic neurologic complications is remote
Recommended
Improved postoperative outcome Equally effective as TEA Trend toward lower incidence of major complications compared with TEA and lower block failure rate Limited value with singleshot injection
Recommendations
Thoracic epidural analgesia (TEA)
Superior analgesia during coughing and physical therapy, and improved postoperative outcome
High (15%) failure rate, complicates postoperative anticoagulation, hypotension, nausea, urinary retention, pruritus, accidental intrathecal spread, epidural hematoma, and epidural abscess
Recommended
Intrathecal opioid analgesia
Better static and dynamic pain scores compared with systemic opioid analgesia specifically in first 24 h postoperatively
Risk of respiratory depression, pruritus, urinary retention, nausea, and vomiting
Recommended, if paravertebral block or TEA is contraindicated or not possible
Intercostal analgesia
Simple and easy to perform, superior pain scores, reduced opioid requirements, and improved postoperative outcome
Systemic local toxicity, better pain scores with continuous catheter, or multiple injections
Recommended in combination with nonopioid analgesics, such as acetaminophen and NSAIDs or COX-2specific inhibitors, if paravertebral block or TEA is contraindicated or not possible
Interpleural analgesia
Easy to perform but not efficacious
Potential of local anesthetic toxicity
Not Recommended
Intercostal nerve cryoanalgesia
Effective in perioperative period in improving pain scores compared with placebo
Implicated in increasing incidence of chronic pain
Not Recommended
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Table 4. Nonopioid Analgesics Systemic Analgesics
Benefits
Risks
Recommendations
Acetaminophen
Safe, effective analgesic and antipyretic Reduces pain scores and opioid requirements No increased incidence in hemorrhage, gastric ulceration, cardiovascular, and renal adverse effects Has “ceiling effect”
Liver toxicity
Recommended in combination with other analgesics
Nonsteroidal antiinflammatory drugs (NSAIDs)
Improves pain relief Reduces opioid consumption by 30% and decreases opioidrelated adverse effects
Impaired coagulation, gastric irritation, renal dysfunction, and cardiovascular adverse effects
Recommended in combination with other analgesics
Cyclooxygenase (COX)-2 Inhibitors
Improves pain scores, decreases opioid consumption, and reduces opioid-related adverse effects Similar efficacy as NSAIDs No effects on platelet function and perioperative bleeding
Potential gastric irritation, renal dysfunction, and cardiovascular adverse effects
Recommended in combination with other analgesics
Glucocorticoids (dexamethasone)
Reduces inflammation, improves pain relief, prolongs time to first analgesic, and modest reduction in opioid requirements
Increase blood glucose levels up to 24 h, but may not be clinically relevant
Recommended as an adjunct
Ketamine
Analgesic properties without respiratory depressive effects, reduces pain scores, and opioid consumption, and prolongs time to first analgesic Optimal dose and duration of administration remain controversial
Sympathomimetic and neurocognitive side effects
Not recommended for routine use
Gabapentinoids (gabapentin and pregabalin)
Reduced pain scores and opioid requirements Optimal dose and duration of administration remain controversial
Sedation, dizziness, and visual disturbances
Not recommended for routine use
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN the combination resulted in lower pain scores at rest, coughing, and mobilization during the first 48 hours postoperative period without increasing perioperative bleeding.10 They also noted that the patient satisfaction scores were greater in the combination group.10 Interestingly, it appears that the relative benefits of TEA in reducing postoperative pulmonary complications have decreased over the last few decades, which is probably due to improved surgical techniques, prophylactic antibiotics, improved postoperative care (eg, avoidance of nasogastric tubes), improved pulmonary physiotherapy, and early mobilization.11 Thus, although the analgesic benefits of TEA have been reported to be favorable in patients with chronic obstructive pulmonary disease,12 its routine use is being increasingly questioned.13-15 Of note, TEA is associated with several potential adverse effects; however, their overall incidence is low (Table 3).
Paravertebral Analgesia Paravertebral block can be performed by administration of local anesthetic in the paravertebral space through a percutaneous posterior approach using either a loss of resistance or ultrasound-guided technique. Alternatively, it can be placed under direct visualization by the surgeon, at the end of surgery.1 Several recent systematic reviews and metaanalysis have found no difference in analgesic efficacy and the need for supplemental opioid requirements between paravertebral analgesia and TEA in patients undergoing thoracic surgery.1,16 In addition, postoperative pulmonary function and incidence of pulmonary complications were also similar between the 2 techniques. Use of paravertebral analgesia avoids the potential complications associated with TEA.1,16,17 A recent observational trial in patients undergoing pneumonectomy explored the effects of paravertebral block and TEA on major postoperative complications, including hypotension requiring inotrope therapy, arrhythmias requiring antiarrhythmic therapy, respiratory complications requiring ventilator support, and the need for further surgery.17 This study found that patients who received TEA had a higher incidence of major complications compared with those patients who received thoracic paravertebral analgesia. Also, occurrence of accidental dural puncture and postdural puncture headache is unlikely with paravertebral block. Furthermore, the potential for catastrophic neurologic injuries resulting from epidural hematoma and abscess is remote with paravertebral analgesia.
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One of the concerns with paravertebral analgesia is that the local anesthetic may spread from the paravertebral space to the epidural space, thus causing the potential complications of epidural analgesia. There appears to be an epidural spread in up to 70% of patients receiving paravertebral analgesia, which is influenced by the technique (eg, ultrasound technique appears to increase the risk of epidural spread) and volume of local anesthetic (eg, single large-volume injection technique is associated with higher spread as opposed to multiple small volumes or continuous infusion) as well as practitioner experience and anatomical deformity, which can influence the local anesthetic spread.18 Nevertheless, most injections resulting in epidural spread have limited side effects, such as transient hypotension and lower limb weakness. However, if the local anesthetic is misplaced in the intrathecal space, total spinal anesthesia requiring tracheal intubation and hemodynamic support may result.18 Other potential complications associated with paravertebral block include vascular and pleural injury, which can increase up to 8-fold with bilateral paravertebral blocks.18 Although the paravertebral space is highly vascular, the likelihood of hematoma formation resulting in significant morbidity is very rare. The block failure rate with thoracic paravertebral blocks is reported to be lower than that with TEA. Because of equivalent analgesic efficacy and superior side effect profile compared with TEA, paravertebral analgesia has recently had a resurgence and is currently recommended over TEA.1 Of note, the use of continuous local anesthetic infusion is preferred, because of superiority over a single injection technique. There appears to be no difference in the choice of local anesthetics, as continuous infusion of bupivacaine, ropivacaine, and lidocaine is equally efficacious. However, longer-acting local anesthetics are recommended for single injection techniques. The addition of fentanyl in combination with local anesthetic in the infusion has been shown to provide similar pain relief compared with local anesthetic alone. Also, the addition of clonidine to local anesthetic has provided contradictory evidence with respect to analgesia and has been reported to increase sedation. Thus, the addition of adjuncts, such as fentanyl and clonidine, to local anesthetic solution is not recommended.
Intrathecal Opioid Analgesia Intrathecal opioid analgesia is an established pain treatment modality in postthoracotomy pain.19 A
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN recent meta-analysis ascertained the efficacy of intrathecal opioids in major surgery, which included cardiothoracic and major abdominal surgery.19 A single dose of intrathecal morphine was able to decrease 24-hour static and movement-related pain intensity scores.19 The risk of respiratory depression from intrathecal morphine ranges from 1.2%-6.7% and can result from even a small dosage such as 200300 mg of morphine.19 Other side effects include pruritus, urinary retention, nausea, and vomiting. The addition of clonidine to intrathecal morphine is not recommended because of minimal benefits and high incidence of hypotension.20 A recent study comparing TEA with paravertebral block combined with intrathecal morphine found that both the techniques provided similar pain relief and thus could be used alternatively.21 However, the need for adding intrathecal morphine with paravertebral block is questionable. Nevertheless, intrathecal opioids can be considered as a part of a multimodal analgesic regimen when regional alternatives such as TEA or paravertebral analgesia are not possible or contraindicated.1
Intercostal Analgesia ICNB have long been used as an analgesic technique for thoracic surgery. These blocks are easier and faster to perform. They can be accomplished by placement of a catheter in the intercostal space at the end of the surgery under direct visualization by the surgeon. A systematic review found reduced postoperative pain scores with ICNB, compared with placebo,1 particularly administered as repeat blocks or continuous infusion. Studies comparing ICNB with TEA have reported conflicting results with respect to pain relief and opioid requirements as well as postoperative pulmonary function.22 However, TEA was associated with a higher incidence of pruritus and need for a urinary catheter.22 Overall, ICNB are an alternative to TEA or paravertebral blocks,1 particularly when those techniques are contraindicated or not possible. Interpleural Analgesia Interpleural analgesia is performed by injecting local anesthetic in the pleural space between the parietal and visceral pleura with the proposed mechanism of action appearing to be diffusion of local anesthetic across the parietal pleura.1 However, this technique is not recommended because of the lack of efficacy compared with other regional techniques, as well as potential toxicity associated with absorption of local anesthetic.1
Intercostal Nerve Cryoanalgesia Cryoanalgesia involves freezing the intercostal nerves resulting in axonal disintegration and degeneration of the myelin sheaths which leads to long-lasting neurolysis and postoperative pain relief.23 Previous studies have reported beneficial analgesic effects of intercostal nerve cryoanalgesia. However, several more recent studies have implicated cryoanalgesia in increasing the incidence of chronic pain and paresthesia.23,24 Thus, intercostal nerve cryoanalgesia is not considered a suitable technique for pain management after thoracic surgery.1 SYSTEMIC ANALGESIC TECHNIQUES Opioid Analgesia Systemic opioids have long been a major component of perioperative pain management. However, there is increased emphasis in reducing the opioid dose owing to concerns of opioid-related adverse events, including hypoventilation, sedation, constipation, nausea, vomiting, pruritus, and interrupted sleep patterns, all of which may contribute to a delayed recovery.1 Thus, it is recommended that nonopioid analgesic techniques should be the first line of therapy with opioids reserved for more severe pain that is not adequately controlled with nonopioids. Acetaminophen Acetaminophen has established itself as a safe and effective analgesic and antipyretic. Although the mechanism of action of acetaminophen remains unclear, its site of action is thought be central in origin (ie, the spinal cord and brain). Acetaminophen is devoid of some of the adverse effects of NSAIDs, such as gastrointestinal ulceration and hemorrhage, cardiorenal adverse effects, and impaired platelet aggregation. However, there is a concern of liver toxicity, particularly in patients with compromised hepatic function, severe alcoholism, cirrhosis, or hepatitis. Importantly, these patients should be warned that commonly used opioid combinations might contain acetaminophen. The Food and Drug Administration in the United States recently approved an intravenous formulation of acetaminophen, although it has been available in Europe for over a decade. Intraoperative administration of IV acetaminophen has been shown to reduce postoperative pain scores and opioid requirements, and has been advocated as a part of a multimodal analgesia technique.25 In intensive care unit patients, IV acetaminophen significantly reduced the time to tracheal extubation with
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Thoracic Paravertebral Analgesia (continued for 48-72 h) Or Thoracic Epidural Analgesia (continued for 48-72 h)
If contraindicated or not possible
Intercostal Nerve Block (continuous infusion for 48-72 h) + Wound infiltration Or Intrathecal Morphine
Combined with
Acetaminophen + NSAIDs or COX-2 specific inhibitors + Opioid (IV-PCA) for “rescue” Consider adding
Dexamethasone as analgesic adjunct
Figure 1. Recommendations for prevention of postthoracotomy pain. IV-PCA, intravenous patient-controlled analgesia. (Color version of figure is available online at http://www.seminthorcardiovascsurg.com.)
superior pain scores compared with placebo.26 Similar to NSAIDs and COX-2-specific inhibitors, acetaminophen also exhibits an analgesic “ceiling” effect.27 The combination of acetaminophen with NSAIDs or COX-2-specific inhibitors has been shown to provide superior analgesia compared with either drug alone.28,29
NSAIDs The mechanism of analgesic effects of NSAIDs is through inhibition of the COX-2 enzyme. The NSAIDs have been shown to reduce postoperative pain as well as opioid requirements and are recommended as an important component of the multimodal analgesia technique. In patients undergoing thoracic surgery, NSAIDs have been shown to reduce opioid consumption by approximately 30%.1,28,29 With the introduction of parenteral preparations of NSAIDs (eg, ketorolac and ibuprofen), this class of drugs has become more popular in the management of postoperative pain. Potential side effects of NSAIDs include impaired coagulation (and increased perioperative bleeding), gastric irritation (particularly when these drugs are administered in fasting patients), and renal dysfunction. Thus, NSAIDs should not be used in patients with preexisting coagulation defects or those undergoing surgical procedures with potential for
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significant bleeding. In addition, NSAIDs should be avoided in patients with preexisting renal dysfunction, hypovolemia, cardiac failure, sepsis, or endstage liver disease.
COX-2-Specific Inhibitors COX-2-specific inhibitors selectively inhibit the COX-2 enzyme and spare the COX-1 enzyme. Thus, COX-2-specific inhibitors lack the antiplatelet effects of the traditional NSAIDs. However, in the perioperative period, the cardiovascular and renal side effect profile of COX-2-specific inhibitors seems to be equivalent to that of nonselective NSAIDs. The analgesic efficacy of COX-2-specific inhibitors is similar to that of the traditional NSAIDs. Thus, the COX-2-specific inhibitors improve pain scores, decrease opioid consumption, and reduce opioidrelated side effects. Because the COX-2-specific inhibitors do not have any antiplatelet effects, there is no concern of increased perioperative bleeding with this group of drugs, and they can be administered preoperatively.1 ANALGESIC ADJUNCTS Glucocorticoids Glucocorticoids have been used to reduce inflammation and tissue damage, which can reduce pain.
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN Multiple studies have noted that single dose of dexamethasone reduced postoperative pain and prolonged time to first analgesic request.30,31 Interestingly, the reduction in opioid consumption at 2 and 24 hours was modest. Although the optimal dosage remains debatable, most studies have used doses of 4-8 mg, IV given either preoperatively or intraoperatively. A single dose of dexamethasone has not been shown to increase the incidence of surgical site infections, but it may increase blood glucose levels lasting for up to 24 hours postoperatively. The clinical significance of this increase in blood glucose levels is not known. Ketamine Ketamine is an N-methyl-D-aspartate antagonist that has analgesic properties without respiratory depressive effects. Several systematic reviews have found that low-dose ketamine reduces postoperative pain scores and opioid consumption as well as delayed time to first opioid administration. A recent systematic review revealed that ketamine provided significant analgesic benefits in painful procedures, including thoracic, upper abdominal, and major orthopedic surgeries.32 Interestingly, the analgesic effects of ketamine were independent of the type of intraoperative opioid administered, timing of ketamine administration, and the ketamine dose. The authors also concluded that the opioid-sparing effects of ketamine reduced the incidence of nausea and vomiting and was associated with an increase in the incidence of neuropsychiatric disturbances.32 Thus, intravenous ketamine may play a role as an adjunct to other nonopioid analgesics, but the optimal dose and duration of administration remain controversial. Similarly, the role of ketamine in reducing postthoracotomy syndrome remains controversial. A recent study found that although ketamine reduced pain in the immediate postoperative period, it did not reduce the incidence of pain at 3 and 6 months after surgery.33 Gabapentoids Both gabapentin and pregabalin are structural analogs of gamma-aminobutyric acid and have the same mechanism of action. They are thought to work through modulating the α-2-δ subunit of voltagegated calcium channels in the dorsal horns of the spinal cord. These drugs are commonly used for the management of neuropathic pain. However, they have also been extensively studied in the perioperative setting. Because persistent postsurgical pain is thought to be neuropathic in nature, theoretically gabapentinoids may be of benefit in its prevention.
Several placebo-controlled randomized trials have reported improved pain scores and reduced opioid requirements with both gabapentin and pregabalin.34,35 A recent systematic review found that perioperative pregabalin reduced opioid consumption and opioid-related adverse effects after surgery.35 However, the incidence of visual disturbances was high. Other side effects of this group of drugs include dizziness and drowsiness. The optimal dose and duration of administration of these drugs remain unknown. These drugs have also been shown to be effective in the treatment of postthoracotomy pain syndrome; however, it remains unclear whether they can prevent this syndrome.
SUMMARY The benefits of optimal pain management are well recognized. These include enhanced recovery and reduced intensive care unit and hospital length of stay. Thus, adequate pain control would improve health care resource utilization and reduce health care costs.2 Based on the current evidence, thoracic paravertebral block and TEA are recommended as the first-choice therapies for postthoracotomy analgesia (Fig. 1). Given the lack of superiority of TEA over paravertebral analgesic and the potential risk of adverse effects of TEA, paravertebral analgesia may offer some advantages. One issue that remains unresolved is the efficacy of neuraxial analgesia techniques (ie, epidural and paravertebral analgesic) in reducing postthoracotomy pain syndrome. When either TEA or paravertebral analgesia is contraindicated or not possible, intercostal analgesia or intrathecal opioids are recommended. These techniques should be combined with nonopioid analgesics, such as acetaminophen, NSAIDs or COX-2-specific inhibitors, and dexamethasone, assuming there are no contraindications, with IV patient-controlled analgesia opioids for rescue. Furthermore, it is imperative that these nonopioid analgesics are administered on a regular “roundthe-clock” basis with opioids used as “rescue” analgesics. The role of ketamine and gabapentinoids remains controversial, and further studies are necessary before these drugs can be recommended for routine use. Nevertheless, these drugs may be beneficial for the patient who is opioid tolerant and those at high risk of persistent postsurgical pain. Finally, the integration of multimodal analgesia techniques with multidisciplinary rehabilitation program can enhance recovery, reduce hospital stay, and facilitate early convalescence.2
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THE STATE OF THE ART IN PREVENTING POSTTHORACOTOMY PAIN 1. Joshi GP, Bonnet F, Shah R, et al: A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia. Anesth Analg 107:1026–1040, 2008 2. Jones NL, Edmonds L, Ghosh S, et al: A review of enhanced recovery for thoracic anaesthesia and surgery. Anaesthesia 68: 179–189, 2013 3. Joshi GP, Ogunnaike B: Consequences of inadequate postoperative pain relief and chronic persistent postoperative pain. Anesthesiol Clin N Am 23:21–36, 2005 4. Kinney MA, Hooten WM, Cassivi SD, et al: Chronic postthoracotomy pain and healthrelated quality of life. Ann Thorac Surg 93: 1242–1247, 2012 5. Kehlet H, Hensen TS, Woolf CJ: Persistent postsurgical pain: Risk factors and prevention. Lancet 367:1618–1625, 2006 6. PROSPECT: Procedure-specific postoperative pain management Available at: www.postop pain.org. 7. Joshi GP: Multimodal analgesia techniques and postoperative rehabilitation. Anesthesiol Clin N Am 23:185–202, 2005 8. Kehlet H, Wilkinson RC, Fischer HB, et al: PROSPECT: Evidence-based, procedurespecific postoperative pain management. Best Prac Res Clin Anesthesiol 21:149–159, 2007 9. Ali M, Winter DC, Hanly AM, et al: Prospective, randomized, controlled trial of thoracic epidural or patient-controlled opiate analgesia on perioperative quality of life. Br J Anaesth 104:292–297, 2010 10. Senard M, Deflandre EP, Ledoux D, et al: Effect of celecoxib combined with thoracic epidural analgesia on pain after thoracotomy. Br J Anaesth 105:196–200, 2010 11. Popping DM, Elia N, Marret E, et al: Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: A meta-analysis. Arch Surg 143: 990–999, 2008 12. Van Lier F, Van Der Geest PJ, Hoeks SE, et al: Epidural analgesia is associated with improved health outcomes of surgical patients with chronic obstructive pulmonary disease. Anesthesiology 115:315–321, 2011 13. Low J, Johnston N, Morris C: Epidural analgesia: First do no harm. Anaesthesia 63:1–3, 2008
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14. Freise H, Van Aken HK: Risks and benefits of thoracic epidural anaesthesia. Br J Anaesth 107: 859–868, 2011 15. Rawal N: Epidural technique for postoperative pain gold standard no more? Reg Anesth Pain Med 37:310–317, 2012 16. Kotze A, Scally A, Howell S: Efficacy and safety of different techniques of paravertebral block for analgesia after thoracotomy: A systematic review and metaregression. Br J Anaesth 103: 626–636, 2009 17. Powell ES, Cook D, Pearce AC, et al: A prospective, multicenter, observational cohort study of analgesia and outcome after pneumonectomy. Br J Anaesth 106:364–370, 2011 18. Chelly JE: Paravertebral blocks. Anesthesiol Clin 30:75–90, 2012 19. Meylan N, Elia N, Lysakowski C, et al: Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: Meta-analysis of randomized trials. Br J Anaesth 102:156–167, 2009 20. Engelman E, Marsala C: Efficacy of adding clonidine to intrathecal morphine in acute postoperative pain: Meta-analysis. Br J Anaesth 110:21–27, 2013 21. Dango S, Harris S, Offner K, et al: Combined paravertebral and intrathecal vs thoracic epidural analgesia for post-thoracotomy pain relief. Br J Anaesth 110:443–449, 2013 22. Meierhenrich R, Hock D, Kuhn S, et al: Analgesia and pulmonary function after lung surgery: Is a single intercostal nerve block plus patient-controlled intravenous morphine as effective as patient-controlled epidural anesthesia? A randomized non-inferiority clinical trial. Br J Anaesth 106:580–589, 2011 23. Ju H, Feng Y, Yang B, et al: Comparison of epidural analgesia and intercostal nerve cryoanalgesia for post-thoracotomy pain control. Eur J Pain 12:378–384, 2008 24. Mustola ST, Lempinen J, Saimanen E, et al: Efficacy of thoracic epidural analgesia with or without intercostal nerve cryoanalgesia for postthoracotomy pain. Ann Thorac Surg 91: 869–873, 2011 25. McNicol ED, Tzortzopoulou A, Cepeda MS, et al: Single-dose intravenous paracetamol or propacetamol for prevention or treatment of
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Seminars in Thoracic and Cardiovascular Surgery Volume 25, Number 2