Poststernotomy Pain: A Clinical Review

REVIEW ARTICLE

Poststernotomy Pain: A Clinical Review Michael Mazzeffi, MD, MPH, and Yury Khelemsky, MD

P

OORLY CONTROLLED PAIN is associated with sympathetic nervous system activation and an increased hormonal stress response. This response may contribute to multiple adverse postoperative events, including myocardial ischemia, cardiac arrhythmias, hypercoagulability, pulmonary complications, and increased rates of delirium and wound infection. In a systematic review of trials that examined postoperative pain and patient outcomes, better pain control was associated with lower rates of cardiovascular complications, pneumonia, and postoperative hypercoagulability.1 According to the American Heart Association, between 1996 and 2006, the total number of cardiovascular operations and procedures performed in the United States increased 33% annually from 5,444,000 to 7,235,000.2 In 2006, an estimated 448,000 coronary artery bypass graft (CABG) operations were performed. Most cardiac surgery is performed through a median sternotomy. Because of the large number of cardiac operations performed annually and the link between optimal postoperative pain management and improved clinical outcome, anesthesiologists must champion the current best practice. Therefore, an evidence-based review of the epidemiology, pathophysiology, and prevention and treatment of both acute and chronic poststernotomy pain is presented. METHODOLOGY FOR THE LITERATURE REVIEW

To identify relevant articles for the review, the web site http://www.pubmed.gov was used to query the following phrases: sternotomy pain, acute sternotomy pain, chronic sternotomy pain, thoracic epidural and sternotomy pain, thoracic epidural and cardiac surgery, spinal anesthesia and sternotomy pain, spinal anesthesia and cardiac surgery, regional anesthesia and sternotomy, regional anesthesia and cardiac surgery, local anesthesia and cardiac surgery, and pain and cardiac surgery. The authors also identified studies of interest from the reference lists in studies that were reviewed. All articles identified were obtained in full text. Both authors agreed on the relevant studies to include in the review.

communicate verbally (eg, tracheostomy or ventilated patients). Pain comparisons among the multiple scales are fraught with difficulty because the scales have various magnitudes or units of measurement. A number of studies have suggested that cardiac surgery patients have significant pain after surgery in both the intensive care unit and after their transfer to the floor.3-5 Recent prospective studies have described the incidence, severity, and risk factors for acute sternotomy pain. In a prospective cohort study of 213 CABG surgery patients, subjects were assessed 4 days after surgery using the VAS.6 In this study, patients experienced more postoperative pain than they anticipated. Forty-nine percent had severe6 pain at rest, 78% had severe pain during coughing, and 62% had severe pain during movement. In another prospective study of 705 cardiac surgery patients, pain related to activity was assessed daily on postoperative days 1 through 6 using the VAS.7 Patients experienced their most severe pain while coughing, followed by moving, turning in bed, getting out of bed, and, finally, during deep breathing. Although pain scores were highest during the immediate postoperative period, patients still reported a mean pain score of 4.33 while coughing and a mean pain score of 3.09 with deep breathing on the sixth postoperative day. In a third prospective study of 200 consecutive patients who had cardiac surgery through a median sternotomy, pain was assessed using VAS on postoperative days 1, 2, 3, and 7.8 In this study, the highest pain scores were recorded on days 1 and 2 (mean of 3.7 and 3.9, respectively) with a significant decrease on day 3 (mean of 3.2) and day 7 (mean of 2.6). It also was noted that the location of the most intense pain changed over time to shoulder pain on postoperative day 7. An Australian study of 102 patients in the intensive care unit after cardiac surgery specifically studied patients’ perceptions about postoperative pain and their overall satisfaction.9 In this

EPIDEMIOLOGY OF ACUTE STERNOTOMY PAIN

The assessment and quantification of acute pain can be highly variable and dependent on the interval of assessment as well as the instrument used for quantification. A number of scales are used in clinical practice to quantify pain. These include the facial expressions scale, the visual analog scale (VAS), numeric rating scales, and verbal rating scales, among others. Certain scales are better suited than others for particular patient populations. For example, the facial expressions scale can be used in patients who are unable to

From the Department of Anesthesiology, Mt Sinai School of Medicine, New York, NY. Address reprint requests to Michael Mazzeffi, MD, MPH, Department of Anesthesiology, One Gustave L Levy Place, Box 1010, New York, NY. E-mail: [email protected] © 2011 Elsevier Inc. All rights reserved. 1053-0770/2506-0045$36.00/0 doi:10.1053/j.jvca.2011.08.001 Key words: sternotomy, pain, cardiac surgery

Journal of Cardiothoracic and Vascular Anesthesia, Vol 25, No 6 (December), 2011: pp 1163-1178

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Fig 1. Simplified pain pathway depicting site(s) of action of common analgesic medications. (Color version of figure is available online.)

study, most patients were satisfied with their pain control. This study showed that females had worse pain after sternotomy, patients who had internal mammary artery harvesting had more intense pain, and elderly patients were denied analgesia more often than young patients. In summary, it appears that many patients experience significantly greater pain than expected after sternotomy. Typically, acute pain is worst on the first postoperative day at the site of surgical incision. Usually, the worst pain is experienced during movement or coughing. Significant pain often continues for up to a week after surgery, and the location of pain may shift during this time period away from the site of surgical incision and to the shoulders. PATHOPHYSIOLOGY OF ACUTE STERNOTOMY PAIN

The mechanisms of postsurgery pain are complex, but generally speaking, in addition to nociceptive input from direct tissue trauma, an inflammatory response leads to the sensitization of peripheral and central pathways resulting in the experience of pain. Most sternotomy pain occurs because of tissue injury in the skin, subcutaneous tissues, bone, and cartilage. Intercostal nerves arising from thoracic nerve roots innervate the sternum, ribs, and surrounding subcutaneous tissue. The principal thoracic nerves supplying the sternum are T2 to T6. The parietal pleura also is innervated densely with pain fibers that can be activated by either mechanical or chemical stimuli.10 In contrast, the visceral pleura does not have significant sensory innervation. The pericardium is innervated with pain fibers that arise from the vagus nerve, phrenic nerve, and sympathetic trunks.11 When tissue injury occurs from surgery, numerous inflammatory mediators are released, including ions (eg, sodium, potassium, and calcium) bradykinin, substance P, histamine,

5-hydroxytryptamine, adenosine triphosphate, nitric oxide, prostanoids, and leukotrienes.12,13 Some of these molecules directly activate nociceptors, whereas others work through indirect mechanisms. These inflammatory molecules also play an important role in the sensitization of both peripheral and central neurons to subsequent stimuli. Primary afferent fibers (A-delta and C) conduct impulses from peripheral nociceptors to the dorsal horn of the spinal cord. From here, sensory information is relayed primarily via the spinothalamic tract to the supraspinal structures, including the brainstem, thalamus, and cortex, where the ultimate experience of pain takes place (Fig 1). It is believed that acute tissue injury occurs after sternotomy not only at the site of surgical incision but also at more distant sites because of prolonged sternal retraction, which may lead to rib fracture, costochondritis, rib joint dislocation, or nerve injury.14 The presence of chest tubes and mediastinal tubes, which irritate the parietal pleura and pericardium, are also a significant source of pain for patients. Finally, pericarditis can occur after pericardiotomy, leading to significant pain. In summary, acute sternotomy pain is mechanistically complex and occurs secondary to tissue injury and inflammation not only at the site of surgical incision but also at distant sites that are injured during prolonged sternal retraction and from the presence of chest and mediastinal tubes. PREVENTION AND TREATMENT OF ACUTE STERNOTOMY PAIN

As mentioned previously, optimal pain management mitigates the stress response to surgery and may improve clinical outcomes for patients although this has been difficult to definitively prove. Poorly controlled pain after surgery has been

POSTSTERNOTOMY PAIN

1165 Table 1. Acute Pain Management Techniques for Sternotomy

Technique

Advantages

Disadvantages and Risks

IV opioids (PCA)

Patient autonomy, rapid onset of effect with most, proven analgesia

TEA

Effectively mitigates stress response to surgery May improve pulmonary function postoperatively Allows for the infusion of local anesthetic, decreasing opioid dosing May improve pulmonary function postoperatively Less requirement for PRN opioids postoperatively Generally low risk Theoretically avoids risk of epidural hematoma or abscess Peripheral and central mechanism of action

Respiratory depression, pruritus, constipation, nausea/vomiting, ileus, urinary retention, sedation, delirium, dysphoria Caution with morphine and meperidine in patients with renal insufficiency Potential for epidural hematoma and abscess Hypotension because of sympathectomy Inadvertent intravascular or intrathecal administration of local anesthetic

Intrathecal anesthesia

Local infiltrative techniques Paravertebral blocks NSAIDs

Gabapentinoids

Acetaminophen Ketamine

TENS

Minimally invasive surgical techniques Preoperative patient education Hospital-wide pain program implementation

May prevent chronic sternotomy pain Addresses neuropathic pain component No respiratory depression Generally low risk NMDA antagonist property provides exceptional analgesia Does not cause respiratory depression Low risk

Potentially decreased postoperative pain Low risk for patients Empowers patients and makes expectations more reasonable Low risk for patients

associated with numerous adverse outcomes, including pulmonary complications, cardiac ischemic events, cardiac arrhythmias, hypercoagulability, and increased rates of wound infection.1 A number of studies have shown that poorly controlled pain is associated with compromised postoperative pulmonary function.15-17 Specifically, there is a restrictive deficit that occurs within the first three postoperative days, with a decrease in vital capacity and other spirometric values of approximately 33%.18-20 Also, there are increases in intrapulmonary shunting and the alveolar-arterial oxygen tension gradient and reductions in arterial oxygen tension.21-23 Few studies have examined the effects of optimal pain management, regardless of technique, on the rates of major complications after cardiac surgery. The difficulty in performing these types of studies is that the inci-

Potential for epidural hematoma and abscess All side effects of opioids as listed above Delayed respiratory depression Intravascular injection Risk of total spinal, epidural, or unintentional pneumothorax or hemothorax Selective COX-2 inhibitors and nonselective NSAIDs at higher doses associated with higher rates of cardiovascular events and thrombosis NSAIDs probably should be avoided in patients with history of myocardial infarction and renal disease Slow onset of analgesia Dizziness or sedation Contraindicated in patients with significant liver disease Dysphoria, hallucinations, excessive salivation, tachycardia Muscle twitching Can lead to electromagnetic interference in patients with pacemakers Surgeon-dependent, possibly associated with higher complication rates Potentially costly and difficult to reach all patients preoperatively Possible costs and resistance to change among hospital staff

dence of major adverse perioperative events is low, and large numbers of patients are required to show small differences in outcomes between groups.1 Regardless of whether optimal pain control improves the previously mentioned clinical outcomes, it remains important because it leads to greater patient satisfaction, which is a critical outcome measure in the era of value-based purchasing. Better pain control also may decrease the length of hospital stay, reducing costs.24-26 Finally, severe acute pain after sternotomy is predictive of chronic pain, which is associated with significant personal and financial costs.27 In the following subsections, individual acute pain management modalities and important considerations for their use in sternotomy patients are described. A summary of these modalities is available in Table 1.

Author (Year)

Patient Population

Study Design

Variables Studied

60

CABG

Randomized comparison between GA v GA ⫹ TEA

Postoperative pulmonary and cardiac function, biochemical markers of stress response, extubation time, and pain scores Pain scores, sedation scores, and time to extubation

Liem (1992)44

54

CABG

Randomized comparison between GA v GA ⫹ TEA

Loick (1999)45

70

CABG

Randomized comparison between GA v GA ⫹ TEA

Pain scores, comfort, sedation, and biomarkers of stress response

Tenling (2000)46

30

CABG

Randomized comparison between GA v GA ⫹ TEA

Preoperative and postoperative PFTs

Dhole (2001)47

41

Midcab

Randomized comparison of GA ⫹ continuous PVB v GA ⫹ TEA

Pain scores.

Scott (2001)48

420

CABG

Randomized comparison between GA v GA ⫹ HTEA

PFTs, respiratory tract infections, extubation time

Fillinger (2002)49

60

CABG

Randomized comparion between GA v GA ⫹ TEA

Time to extubation, ICU length of stay, pain scores, biochemical markers of stress response

Priestly (2002)50

100

CABG

Randomized comparison between GA v GA ⫹ HTEA

Pain scores, extubation time, and length of stay

0.1 mg/h epidural morphine

Insertion at T1-T2 interspace, infusion of 0.125% bupivacaine with sufentanil 1: 1 million @ 0.05 mL/ cm body length/h Insertion at C7-C8 or C8-T1 level, 8-12 mL bolus of 0.375% bupivacaine with 16-24 ␮g of sufentanil Infusion of 0.75% bupivacaine with or without sufentanil @ 3 mL/h T3-T4 or T4-T5 insertion. Bolus 8 to 12 mL of 0.5% bupivacaine on the morning of operation 4-8 mL/h until arrival in the ICU Insertion at T4-T5 level, 8-mL bolus of 0.5% bupivacaine 0.25% bupivacaine @ 6 mL/h in both groups Insertion at T2-T3 or T3-T4, bolus of 10 mL of 0.5% bupivacaine Infusion of 0.125% bupivacaine with 0.0006% clonidine @ 10 mL/h Discontinued after 96 h. 20 ␮g/kg of morphine and 25-35 mg of bupivacaine loading dose Continuous infusion of 0.5% bupivacaine with morphine, 25 ␮g/ mL @ 4-10 mL/h for 24 h postoperatively Insertion at T1-T2, T2-T3, or T3-T4. Bolus 4 mL of 1% ropivacaine and 100 ␮g of fentanyl before surgery Infusion 1% ropivacaine with 5 ␮g/mL of fentanyl @ 3-5 mL/h until POD 2

Major Findings

Lower pain scores in TEA group Earlier extubation in TEA group Lower levels of biochemical stress markers in TEA group No major complications TEA group had earlier extubation, lower pain scores, and less tachycardia No major complications TEA groups had lower pain scores and lower levels of stress biomarkers. No major complications

Greater expiratory force achieved in TEA group postoperatively, breathing at rest unaffected No complications No differences in pain scores No major complications

Faster extubation in TEA group Fewer respiratory infections and improved PFTs in TEA group No major complications No significant differences in study variables No major complications

TEA group had lower pain scores and faster extubation No difference in length of stay No major complications

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El-Baz (1987)43

TEA Details

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Table 2. Randomized, Controlled Trials Evaluating TEA and Postoperative Pain or Pulmonary Function in Cardiac Surgery Patients Number of Subjects

80

CABG

Randomized comparison between GA v GA ⫹ HTEA

Pain scores, psychologic morbidity, hemodynamics, pulmonary and cardiac function

Insertion at T1-T2 or T2-T3 level, bolus of 8 mL of 0.5% ropivacaine with 2 ␮g/mL of fentanyl at surgery start Infusion of 5-14 mL/h, ceased POD 3

Barrington (2005)52

120

CABG

Randomized comparison between GA v GA ⫹ TEA

Pain scores, extubation time

Hansdottir (2006)53

113

Mixed cardiac surgery population

Randomized comparison between GA v GA ⫹ HTEA

Length of stay, time to eligible discharge, pain scores, sedation scores, lung volumes

Tenenbein (2008)54

50

CABG

Randomized comparison between GA v GA ⫹ TEA

Pain scores, spirometry values, atelectasis on CXR

Mehta (2010)55

62

OPCAB

Randomized comparison between GA v. GA ⫹ HTEA

Preoperative and postoperative PFTs for 5 days. Pain scores.

Sharma (2010)56

60

OPCAB

Randomized comparison between GA v GA ⫹ TEA

Preoperative and postoperative PFTs for 5 days, pain scores

0.2% ropivacaine with 2 ␮g/mL of fentanyl infused 1 h after induction until POD 2 T2-T3, T3-T4, or T4-T5 insertion At start of surgery 0.1- mL/kg bolus of 0.5% bupivacaine 0.05-mL/kg/h infusion of 0.1% bupivacaine with 2 ␮g/mL of fentanyl T2-T3, T3-T4, T4-T5 insertion, 5-mL bolus of 0.75% ropivacaine preoperatively ⫹ 200 ␮g of hydromorphone Infusion of 0.75% ropivacaine @ 5 mL/ h during surgery Postoperative 0.2% ropivacaine with 15 ␮g/mL of hydromorphone until POD 2 Insertion C7-C8, C8-T1, or T1-T2; 8- to 10-mL bolus of 0.25% bupivacaine before surgery Infusion 0.125% bupivacaine with 1 ␮g/mL of fentanyl @ 5 mL/h until postoperative day 3 Insertion C7-C8, C8-T1, T1-T2; 8- to 10-mL bolus of 0.25% bupivacaine before surgery Infusion 0.125% bupivacaine with 1 ␮g/mL of fentanyl @ 5 mL/h until postoperative day 3

Lower pain scores, improved PFTs, and earlier extubation in HTEA group More positive psychological profile in HTEA group Lower MAP in HTEA group No major complications Faster extubation in TEA group Lower pain scores in TEA group No major complications Faster extubation in TEA group Pain scores, sedation, and lung volumes similar between groups, length of stay and time to eligible discharge similar Trend towards lower PNA in TEA group No major complications TEA group had lower pain scores, decreased atelectasis, and better PFTs No major complications

POSTSTERNOTOMY PAIN

Royse (2003)51

HTEA group had earlier extubation, lower pain scores at rest and during coughing; PFTs improved in HTEA faster No major complications TEA group had a shorter ICU stay and earlier extubation; also had lower pain scores and improved PFTs and PO2/ FIO2 ratio No major complications

NOTE. All trials have at least 30 subjects. Abbreviations: GA, general anesthesia; TEA, thoracic epidural anesthesia; HTEA, high thoracic epidural anesthesia; PFTs, pulmonary function tests; PVB, paravertebral block; OPCAB, off-pump coronary artery bypass.

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Opioid Analgesics Patient-controlled intravenous analgesia (PCA) has been used widely since the 1980s and generally is recognized as a safe and effective method of postoperative pain control.28,29 PCA has been compared specifically against nurse-controlled anesthesia in poststernotomy patients and was found to be superior.30 The use of PCA in postoperative cardiac surgery patients is viewed positively by nursing staff because it reduces their workload and increases patient confidence.31 Few studies have compared the efficacy of different postoperative PCA regimens in cardiac surgery patients having sternotomy. In one small, randomized trial, 50 patients in 5 drug groups were compared: morphine, fentanyl, meperidine, remifentanil, and tramadol.32 VAS was used to assess pain over a 24-hour period. In this study, there were no significant differences in pain scores among groups except for those patients receiving tramadol who had the highest pain scores. Meperidine required the least number of bolus doses. Patients who received fentanyl by PCA had significantly higher arterial oxygen tensions than those who received other drugs, implying less respiratory depression. Another randomized trial compared 3 intravenous opioid PCA regimens using remifentanil, morphine, and fentanyl.33 All 3 regimens had both a background infusion and bolus doses. Pain was assessed using VAS. In this study, total boluses were greater in the remifentanil group. There were no significant differences in pain scores; however, the morphine group had a higher incidence of nausea and vomiting, whereas the fentanyl group had the highest rate of pruritus. Alfentanil administered by target-controlled infusion has been evaluated as a postoperative analgesic and was compared with morphine given by PCA in a trial of 120 patients.34 Alfentanil is unique in that it has a high percentage of drug in the unionized form at a physiologic pH, which results in the rapid onset of analgesia. In this study, patients receiving alfentanil had significantly lower pain scores and were extubated more quickly than those receiving morphine. There were no significant differences between groups in the incidence of nausea and vomiting or sedation scores. It is unclear if basal opioid infusions are beneficial in this context. In a study of 60 adult patients receiving intravenous morphine for postoperative sternotomy pain, subjects received either morphine boluses alone or a background infusion with bolus doses.35 In this study, sedation scores did not differ between groups, there were no episodes of hypoxemia, and pain scores were lower in the background plus bolus group. In a similar randomized trial of 100 patients, intravenous morphine with a background infusion plus bolus doses was compared with only bolus-dose morphine.36 In this study, there were no differences in pain scores or side effects between groups. A third trial compared 35 adults after cardiac surgery and similarly found no benefit from a background infusion of morphine when compared with only bolus doses.37 Tramadol is a unique analgesic compound that imparts its action via a weak opioid-receptor agonism and serotonin/norepinephrine reuptake inhibition.38 It has been evaluated as both a primary analgesic and an adjunct to more potent opioids in patients undergoing sternotomy.39 When evaluated as an ad-

MAZZEFFI AND KHELEMSKY

junct to intravenous morphine, tramadol administration resulted in lower pain scores and morphine requirements.40 However, as previously mentioned, tramadol, when used alone, appeared to be inferior to other opioid drugs in treating poststernotomy pain. Opioids are associated with a number of adverse side effects, including respiratory depression, pruritus, nausea/vomiting, constipation, bronchospasm, and hypotension, among others. The avoidance of morphine may be prudent in patients with renal insufficiency because the accumulation of metabolites can result in oversedation and respiratory depression. In summary, intravenous opioids are most efficacious for treating poststernotomy pain when administered by PCA. There does not appear to be a clinically significant difference in efficacy among opioids, and current evidence does not support the use of basal infusions in addition to bolus doses. When selecting a particular opioid analgesic, the drug’s potential adverse effects should be considered first; but if multiple drugs are appropriate, cost should be a secondary consideration because there is a large variation in cost among drugs. Thoracic Epidural Anesthesia Thoracic epidural anesthesia (TEA) has been studied as an adjunct to general anesthesia in cardiac surgery and has a number of potential benefits; however, an anonymous survey indicated that it is used by only about 7% of anesthesiologists caring for cardiac surgery patients.41 The benefits include a reduced risk of postoperative cardiac arrhythmia, reduced pulmonary complications, shortened time to extubation, and reduced pain scores. However, TEA does not appear to reduce the risk of postoperative mortality or myocardial infarction in cardiac surgery patients.42 Over the last two decades, there have been a number of randomized trials that have suggested that TEA can decrease postoperative pain and improve postoperative pulmonary function (Table 2).43-56 Specifically, TEA decreases the amount of atelectasis and improves the forced expiratory volume and force. Other studies have shown that TEA effectively can mitigate the neuroendocrine response to surgery although the relationship between this reduction and morbidity and mortality remains unclear.57,58 The use of TEA also has been associated with a reduced risk of depression after cardiac surgery, which may be related to decreased pain levels.59 Two studies examined the hypothesis that TEA could prevent chronic sternotomy pain after surgery, and both found no protective effect.60,61 The risk-to-benefit ratio of TEA used for cardiac surgery procedures has been a matter of intense debate.62,63 The most feared and severe complication that can occur is the formation of an epidural hematoma leading to neurologic compromise. A recent review of published trials found that the risk of epidural hematoma in cardiac surgery is approximately 1 in 12,000.64 Nevertheless, because the consequences of an epidural hematoma are so severe, TEA in cardiac surgery remains an underused technique for postoperative pain management. Other potential complications are related to the choice of drug that is administered in the epidural space. If morphine is used, there is a risk of delayed respiratory depression. If local anesthetics are used, the risks include inadvertent intrathecal or intravascular

POSTSTERNOTOMY PAIN

injection and hypotension. The use of clonidine increases the risk of bradycardia.65 Intrathecal Analgesia In 1979, Wang et al66 described the first clinical use of intrathecal morphine in a group of 8 patients with genitourinary malignancies. Since that time, intrathecal opioids have been used extensively in clinical practice. Opioids enact profound spinal analgesia by binding to receptors in Rexed laminae I and II of the spinal cord. The physiochemical properties of an individual opioid determine its onset, duration, and potency.67 Drugs that are more hydrophilic have a slower onset and a longer duration of action. The potency of intrathecal opioids also increases with hydrophilicity.68 Morphine, in particular, has been studied in a variety of clinical settings and has been shown to have a long cord exposure time with a slow decline of cerebrospinal fluid concentrations. Intrathecal opioids are associated with significant side effects, including sedation, sweating, urinary retention, pruritus, nausea and vomiting, and respiratory depression. A number of randomized clinical trials have evaluated the use of intrathecal anesthesia as an adjunct to general anesthesia in cardiac surgery over the last two decades (Table 3).69-89 Most of these trials evaluated intrathecal morphine alone; however, a number of them evaluated intrathecal morphine in combination with clonidine. The dose ranges used have varied tremendously over the years with a trend toward using lower morphine doses over time. This is largely because the earliest trials performed found that high-dose intrathecal morphine produced significant and prolonged respiratory depression. Most of these trials showed improved postoperative pain control and reduced postoperative intravenous opioid requirements when intrathecal morphine was administered. Several trials also showed improved postoperative pulmonary function.69,72,82 However, intrathecal morphine does not appear to blunt the stress response to cardiac surgery as effectively as epidural anesthesia.73 In 4 randomized trials, intrathecal clonidine was shown to have significant analgesic properties after cardiac surgery.81,83,87,88 In 2 of these trials, the addition of clonidine to the intrathecal regimen resulted in earlier extubation.83,88 As with epidural anesthesia, intrathecal analgesia poses a risk of epidural hematoma, albeit a smaller one. Intrathecal opioids also may lead to high rates of pruritus, nausea, and urinary retention.90 In summary, intrathecal opioids appear to be effective in providing postoperative analgesia and improving postoperative pulmonary function after cardiac surgery. Spinal administration still carries a risk of epidural hematoma and results in relatively high rates of side effects, which may be mitigated by using lower drug doses.

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trial of bilateral parasternal intercostal nerve blocks (5 levels with a total of 40 mL of 0.75% ropivacaine) revealed significantly reduced pain scores and opioid use after sternotomy.91 Several small studies have evaluated the efficacy of either a single injection of local anesthetic along the sternotomy wound or a continuous infusion of local anesthetic along the sternotomy wound. These studies have yielded mixed results. A few studies showed beneficial effects with decreased postoperative opioid requirements, improved pain scores, and a decreased length of hospital stay.92-96 Another study showed no improvement in postoperative pain scores, extubation time, or arterial blood gas parameters when using 0.5% bupivacaine to infiltrate the wound site as compared with controls.97 No study to the authors’ knowledge directly compared single-shot blocks with continuous infiltration so no definitive statement can be made about the superiority of either technique. Paravertebral blocks have been used to provide analgesia after a variety of surgical procedures, including breast surgery, lung surgery via thoracotomy, minimally invasive cardiac surgery via thoracotomy, and abdominal surgery. The thoracic paravertebral space is a small triangular space containing the spinal nerves. It is bounded by the parietal pleura, transverse process of the vertebra, and paravertebral muscles. Both ultrasounded-guided and nonultrasound-guided techniques (eg, loss of resistance to saline or air and nerve stimulation) have been described for performing these blocks. Typically, 15 to 20 mL of local anesthetic are injected to provide ipsilateral anesthesia over the corresponding thoracic dermatomes. Bilateral blocks also may be performed safely.98 A single study in which bilateral blocks were performed with 0.2% ropivacaine showed excellent analgesia without reported complications for patients who had cardiac surgery via median sternotomy.99 Single-shot paravertebral blocks (or infusions via an indwelling catheter) may have an advantage over thoracic epidural anesthesia in that they may be performed in anticoagulated patients without the risk of epidural hematoma. However, these procedures may result in pneumothorax, intravascular injection, epidural spread of anesthetic, Horner syndrome, and pulmonary hemorrhage. Bilateral paravertebral block for sternotomy pain is an area that requires future investigation to clarify both efficacy and safety. In summary, there may be an advantage to local anesthetic infiltration for sternotomy pain (eg, opioid sparing, improved analgesia). Based on available evidence, it is unclear if continuous infusions of local anesthetic at the sternotomy site are superior to a single-shot injection. Bilateral paravertebral blocks or continuous paravertebral catheter infusions are techniques that may be beneficial for patients having sternotomy but have not been studied extensively. Adjunct Pharmacologic Therapies

Other Regional Anesthesia and Infiltrative Techniques In addition to the previously described neuraxial techniques, local anesthetic blocks have been described as an adjunctive therapy for managing poststernotomy pain. These techniques include intercostal nerve blocks, “single-shot” wound infiltration, continuous local anesthetic infusion at the wound site, and paravertebral blocks. A double-blind, randomized, controlled

A number of nonopioid analgesic drugs have been evaluated as adjuncts in managing poststernotomy pain. Intravenous paracetamol in a dose of 1 g every 6 hours was evaluated as an adjunct in a randomized controlled study of 113 patients. The study found that paracetamol decreased pain scores and tramadol requirements postoperatively.100 A second randomized controlled study evaluated intravenous propacetamol in a dose of 2 g every 6 hours as an adjunct to oxycodone. This study

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Table 3. Randomized, Controlled Trials Evaluating Intrathecal Anesthesia (ITA) and Postoperative Pain or Pulmonary Function in Cardiac Surgery Author (Year)

Number of Subjects

Patient Population

Study Design

60

Casey (1987)70

40

Mixed cardiac surgery CABG

Vanstrum (1988)71

30

CABG

Randomized comparison of GA v GA ⫹ ITA

Fitzpatrick (1988)72

40

CABG

Randomized comparison of GA v GA ⫹ ITA

Chaney (1996)73

60

CABG

Randomized comparison of GA v GA ⫹ ITA

Chaney (1997)74

40

CABG

Randomized comparison of GA v GA ⫹ ITA

Chaney (1999)75

40

CABG

Randomized comparison of GA v GA ⫹ ITA

Zarate (2000)76

40

CABG

Randomized comparison of GA v GA ⫹ ITA

Latham (2000)77

40

Randomized comparison of GA v GA ⫹ ITA

Allhashemi (2000)78

50

Mixed cardiac surgery CABG

Boulanger (2002)79

62

Mixed cardiac surgery

Variables Studied

Intrathecal Drug Used

Randomized comparison of GA v GA ⫹ ITA

Pain scores, PFTs

2 mg or 4 mg of morphine

Randomized comparison of GA v GA ⫹ ITA

Postoperative opioid requirements, hemodynamics, and PFTs Postoperative opioid consumption, postoperative hemodynamics Pain scores, PFTs, ABGs, and opioid consumption postoperatively

20 ␮g/kg of morphine

Postoperative opioid requirements and postoperative catecholamine levels Time to extubation, postoperative opioid consumption Time to extubation and postoperative opioid consumption Time to extubation, pain scores, postoperative opioid consumption, and patient satisfaction Recovery time, hemodynamic stability, and extubation time

4 mg of morphine

Randomized comparison of GA v GA ⫹ ITA

Time to extubation, hemodynamics, and, postoperative opioid consumption

250 ␮g and 500 ␮g of morphine

Randomized comparison of GA v GA ⫹ ITA

Pain scores, extubation times, postoperative recovery, and patient satisfaction

20 ␮g/kg up to 1 mg max of morphine

500 ␮g of morphine 1 mg or 2 mg of morphine

10 ␮g/kg of morphine 10 ␮g/kg of morphine 8 ␮g/kg of morphine

8 ␮g/kg of morphine

Major Findings

ITA group had lower pain scores and better PFTs postoperatively, high rates of nausea and pruritus No difference in opioid requirements, PFTs, or hemodynamics ITA group received fewer opioids postoperatively and had less hypertension ITA had lower pain scores, less opioid requirement, and improved PFTs postoperatively, less respiratory depression in 1-mg group Lower postoperative opioid requirement in ITA group No differences in catecholamine levels No difference in postoperative opioid consumption, longer time to extubation in ITA group No difference in postoperative opioid consumption, no difference in extubaton time ITA group had lower pain scores, lower opioid consumption, and greater satisfaction; no difference in extubation time No difference between groups

No clinically relevant difference in extubation time, decreased postoperative opioid requirement in ITA group, no differences in hemodynamics No differences between groups

MAZZEFFI AND KHELEMSKY

Aun (1985)69

37

CABG

Randomized comparison of GA v GA ⫹ ITA Randomized comparison of GA v. GA ⫹ ITA (morphine only) v GA ⫹ ITA (morphine ⫹ clonidine)

Pain scores, extubation time

2 mg of morphine

45

CABG

Pain scores, opioid consumption

4 ␮g/kg of morphine, 1 ␮g/ kg of clonidine

Mehta (2004)82

100

OPCAB

Randomized comparison of GA v GA ⫹ ITA

Time to extubation, PFTs, and pain scores

8 ␮g/kg of morphine

Lena (2005)83

40

CABG

Randomized comparison of GA v GA ⫹ ITA

Pain scores, opioid consumption, and extubation time

Turker 200584

46

OPCAB

Randomized comparison of GA v GA ⫹ ITA

Hemodynamic profile, recovery time, and pain scores

4 ␮g/kg of morphine and 1 ␮g/kg of clonidine 10 ␮g/kg of morphine

Jacobsohn (2005)85

43

Randomized comparison of GA v GA ⫹ ITA

30

Pain scores, PFTs, Mini-Mental Status Examination, and patient satisfaction Postoperative analgesia, PFTs, stress response, and recovery profile

6 ␮g/kg of morphine

Roediger (2006)86

CABG or single valve CABG

Lena (2008)87

83

CABG or valve procedures

Randomized comparison of GA v GA ⫹ ITA

Pain scores, quality-of-life indicators, and recovery time

Nader (2009)88

85

CABG

Pain scores, extubation times, and opioid consumption

Dos Santos (2009)89

42

CABG

Randomized comparison of GA ⫹ ITA (morphine only) v GA ⫹ ITA (morphine ⫹ clonidine) Randomized comparison of GA v GA ⫹ ITA

4 ␮g/kg of morphine and 1 ␮g/kg of clonidine 500 ␮g of morphine and 100 ␮g of clonidine

Randomized comparison of GA v GA ⫹ ITA

PFTs, pain scores, and opioid consumption

500 ␮g of morphine

400 ␮g of morphine

Lower pain scores in ITA group and similar extubation times Opioid consumption less in ITA (morphine ⫹ clonidine) group, pain scores lower in ITA (morphine ⫹ clonidine) group, time to extubation less in ITA (morphine ⫹ clonidine) group Earlier extubation, improved PFTs, and lower pain scores in ITA group Lower opioid consumption, lower pain scores, and faster extubation in ITA group

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Lenkutis 200280 Lena (2003)81

Lower pain scores in ITA group; similar recovery profile, hemodynamics, and extubation time Improved pain control and better PFTs in ITA group, but no difference in extubation time Lower pain scores and improved PFTs in ITA group, lower catecholamine release in ITA group Lower pain scores and better quality of life indicators in ITA group Addition of clonidine to neuraxial intrathecal morphine improved analgesia and expedited extubation Lower pain scores and opioid consumption in ITA group No significant differences in PFTs between groups

NOTE. All trials have at least 30 subjects. Abbreviations: ABG, arterial blood gas; GA, general anesthesia; ITA, intrathecal anesthesia; PFTs, pulmonary function test. 1171

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showed no differences in pain scores and no major differences in opioid requirements between groups.101 Nonsteroidal anti-inflammatory drugs (NSAIDs) also have been evaluated as an adjunct to opioid analgesics. Diclofenac is an NSAID drug with approximately 10-to-1 specificity for the cyclooxygenase (COX)-2 isoenzyme as compared with COX-1. In a trial of 60 patients, a dose of 100 mg of rectal diclofenac given every 18 hours showed a significant improvement in postoperative pain scores, earlier extubation times, and decreased opioid consumption.102 There was no increase in bleeding attributed to the drug. Other NSAID drugs that have high COX-2 selectivity, including parecoxib and valdecoxib, have been evaluated as adjuncts to opioid analgesics in managing poststernotomy pain. In a large randomized trial, which evaluated COX-2–inhibiting drugs in cardiac surgery, both parecoxib and valdecoxib decreased postoperative pain scores and postoperative opioid requirements.103 However, they were associated with a significantly higher rate of sternal wound infection. They also are associated with higher rates of thrombotic and cardiovascular events after CABG surgery.104 At the present time, neither drug is available in the United States because of serious safety concerns related to cardiovascular events. Although celecoxib, a COX-2 inhibitor, is available in the United States, it is not used for poststernotomy pain given the unfavorable risk-to-benefit ratio. However, all NSAIDs should be used with caution in this patient population because a recent study found that even short-term treatment with most NSAIDs was associated with an increased risk of death and recurrent myocardial infarction in patients with prior myocardial infarction.105 Gabapentin is a GABA analog drug that was developed for the treatment of seizures but now is used commonly in the management of both acute and chronic pain. It appears to function through interaction with voltage-dependent calcium channels in the central nervous system.106 Its efficacy in alleviating acute poststernotomy pain has been evaluated in several small clinical trials. In one trial of 40 patients undergoing CABG surgery, it lowered pain scores and decreased opioid consumption. It also lowered the incidence of chronic poststernotomy pain at 3 months. The dose evaluated was 1,200 mg/d for one day preoperatively and 2 days postoperatively.107 In another small trial that included 60 CABG patients, a single dose of 600 mg decreased postoperative morphine consumption and decreased pain scores.108 In a randomized trial that included 60 CABG surgery patients, gabapentin was given preoperatively as a 1,200-mg dose and postoperatively as a daily dose of 600 mg for 2 days. In this study, however, there was no significant effect on pain scores or quality of recovery when compared with placebo.109 Other drugs that have shown some efficacy as adjuncts in reducing pain scores and opioid consumption include intravenous magnesium (likely via NMDA antagonism) and intravenous ketamine in a bolus dose of 75 ␮g/kg followed by a continuous infusion of 1.25 ␮g/kg/min.110,111 Adjunct Nonpharmacologic Therapies Transcutaneous Electrical Nerve Stimulation Transcutaneous electrical nerve stimulation (TENS) has been used since the early 1970s as an adjunctive therapy for pain management. TENS works by applying a mild electrical

MAZZEFFI AND KHELEMSKY

impulse to the skin, which modifies the body’s perception of pain. It is based on the “gate-control” theory of pain first described by by Melzack and Wall. The sensation of pain is carried into the central nervous system by unmyelinated C fibers and small myelinated A-delta fibers. According to the gate theory, when there is simultaneous input from large myelinated nerve fibers, it can antagonize the input from pain fibers into the central nervous system. Several studies have evaluated TENS as an adjunctive therapy in poststernotomy pain management and found some benefit.112 In one randomized study of 45 patients, TENS improved postoperative pain management and pulmonary function.113 Another large randomized study of 100 patients found decreased pain scores as compared with placebo with no difference between intermittent and continuous TENS.114 PREOPERATIVE PATIENT EDUCATION

In a randomized trial at a large cardiovascular center in Canada, patients were randomized to receive preoperative education on pain management or standard hospital care.115 Those patients who received preoperative pain education received significantly more pain medicine during their hospital stay and had fewer concerns about requesting or taking pain medications. The implication of this study is that patients may require education about postoperative pain control to achieve maximum benefit. PROGRAM IMPLEMENTATION

The implementation of departmental or hospital-wide programs can have a significant impact on outcomes. Several studies have shown improved pain scores and patient satisfaction with the implementation of specific programs or algorithms for managing postoperative pain.116-118 ELECTROACUPUNCTURE

Electroacupuncture was used as an adjunct in managing poststernotomy pain as far back as the 1970s.119 Electroacupuncture is performed by inserting small needles into the skin at specific acupuncture points and stimulating them with electrical current. The mechanism by which this treatment alleviates pain is not understood fully but may involve the release of endogenous opioids. One small, randomized trial of 30 patients showed a benefit of electroacupuncture in reducing poststernotomy pain and improving pulmonary function.120 SURGICAL TECHNIQUE

Several studies have evaluated surgical variables and their impact on postoperative pain after sternotomy. In particular, recent studies have examined the impact of performing surgery through a “mini” sternotomy as compared with a standard or “full-length” sternotomy. Results have varied, with some studies showing a decrease in postoperative pain and others showing no benefit.121-124 Alternative minimally invasive techniques for surgery also may provide a pain benefit. These techniques include but are not limited to minimally invasive mitral valve surgery125 and minimally invasive CABG surgery.126,127 The force applied to the sternum by retractors may be an important factor in sternotomy pain that commonly is over-

POSTSTERNOTOMY PAIN

looked and relatively controllable. In a small animal study, a novel instrumented retractor was tested.128 This retractor gave real-time feedback to the surgeon as the sternum was spread. Essentially, this allowed for the same exposure as a traditional retractor, but it occurred at a slower rate because the device provided information on how much force was being applied. A less forceful retraction theoretically could lead to less poststernotomy pain, but to the authors’ knowledge, this has not been shown clinically. The early removal of chest tubes, on the first postoperative day as compared with the third postoperative day, also has been shown to decrease poststernotomy pain without any adverse side effects. In a randomized study of 80 patients, the group with early removal had less pain in the epigastrum, thorax, and shoulder on the third postoperative day.129 A final surgical variable that has been shown to decrease poststernotomy pain is preservation of the pleura, which both decreases postoperative pain and improves postoperative pulmonary function.130 EPIDEMIOLOGY OF CHRONIC POSTSTERNOTOMY PAIN

Chronic chest wall pain after sternotomy is common, with an estimated prevalence between 11% and 56%.131-140 Most studies evaluating chronic poststernotomy pain focused on CABG surgery patients between 2 months and 3 years after surgery. Factors that appear to be associated with persistent pain include a large chest circumference, obesity, internal mammary artery harvesting, young age, and an increased requirement for postoperative analgesics during the immediate postoperative period. The quality of poststernotomy pain is highly variable, but many patients have at least moderate pain, which commonly affects their quality of life. Midline and left-sided pain appear to be more common than right-sided pain. Although it is well established that chronic pain is more common in patients who have internal mammary artery grafting, it is not clear if a unique clinical syndrome exists separate from other chronic poststernotomy pain. A specific syndrome of chronic pain after internal mammary artery grafting was first described in a case series of 11 Canadian patients in 1989.141 All patients had pain at the site of artery harvesting that was relieved by sympathetic ganglia block. The authors concluded that this syndrome might be caused by damage to the intercostal nerves. In a large CABG surgery cohort, the estimated prevalence of internal mammary artery syndrome (using specific criteria) was 8% compared with an overall incidence of chronic poststernotomy pain of 25%.135 Myofascial pain also is common after sternotomy and may contribute to chronic poststernotomy pain. In a 2008 study, 1,226 patients were evaluated for myofascial pain after sternotomy.142 Trigger points in both the upper trapezius and pectoralis major muscles were tested according to Simons and Gerwin diagnostic criteria. Overall, the incidence of myofascial pain was 15.8%, but among patients who had internal mammary artery harvesting, the rate was 75.5%. Trigger points were found more commonly on the left side in this group of patients. PATHOPHYSIOLOGY OF CHRONIC POSTSTERNOTOMY PAIN

The pathophysiology of chronic pain after sternotomy is complex, and its mechanisms are described poorly in the liter-

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ature. Possible etiologies include sternal malunion, retained pacing wire fragments, and chronic inflammation caused by the presence of sternal wires. Additionally, an allergic reaction to nickel in sternal wires has been implicated as a possible etiology.143 Neuropathic pain from intercostal nerve damage likely plays an important role in chronic poststernotomy pain as well. Intercostal nerves can be damaged either by direct surgical trauma (eg, incision and electrocautery) or indirect damage (eg, ischemia and stretching during retraction). Intercostal nerves may be particularly susceptible to injury during harvesting of the internal mammary artery, which may account for the higher prevalence of chronic pain in patients who require it. Neuropathic pain has both peripheral and central mechanisms. The regeneration of damaged nerves can result in the formation of neuromas and the generation of new nerve endings in neighboring nerves.144,145 This can result in an altered sensorium in the affected area. Additionally, there can be uncontrolled neuronal firing in the injured area because of an increased expression of sodium channels, calcium channels, and demyelination.146 Repeated painful peripheral stimuli result in central nervous system alterations. When neurons in the dorsal root are repeatedly stimulated, a progressive increase in the number of action potentials generated by interneurons occurs.147 This phenomenon commonly is referred to as “wind-up.” It can result in an increased response to painful stimuli or a painful response to a normally innocuous stimulus. The NDMA receptor appears to have an important role in central sensitization and may be a useful target in preventing it.148,149 NMDA activation leads to calcium entry into neurons in the dorsal horn.150 This results in an activation of nitric oxide synthase and an increase in the synthesis of nitric oxide.151 It appears that nitric oxide can enhance the release of substance P, contributing to central sensitization and the development of chronic pain.152 PREVENTION AND TREATMENT OF CHRONIC PAIN

Limited evidence suggests that the development of chronic pain may be reduced by the implementation of specific anesthetic techniques.153-155 In particular, pain thresholds and the area of hyperalgesia after surgery may be altered depending on the anesthetic technique.156-160 The rationale for this is that certain anesthetic drugs or techniques may limit central and peripheral sensitization, which may lower the incidence or decrease the severity of chronic pain.161 It seems that the anesthetic technique carries more significance than its timing because systematic reviews of “pre-emptive” analgesia have found no clinical benefit.162,163 Hence, the term “protective analgesia” has been used to describe techniques that may limit the development of pathologic chronic pain by altering neuronal plasticity and sensitization. At present, there is extremely limited evidence to support any protective analgesic regimen in cardiac surgery that requires sternotomy. Gabapentin was studied in a small trial of 40 patients, and no benefit was shown.102 Thoracic epidural also has shown limited benefit in preventing chronic sternotomy pain.164,165 Both gabapentin and diclofenac appear to be effective in treating chronic sternotomy pain once it has developed; however, gabapentin provides superior analgesia with a more sus-

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tained effect after discontinuation.166 Other medications, such as pregabalin, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, lidocaine patches, and tramadol, also might be effective because they generally are used in the treatment of neuropathic pain syndromes.167 High-quality evidence does not exist for the use of chronic opioids in noncancer pain. One prominent pain society’s recent comprehensive review of the literature found very limited weak evidence for chronic opioid use, urging practitioners to use these medications with “great restraint and caution.”168,169 When medical therapy does not confer pain relief, minimally invasive interventional techniques, such as intercostal nerve blocks and pulsed radiofrequency of the dorsal root ganglion may be attempted.170,171 Epidural injections also may be helpful in alleviating certain types of thoracic pain; however, there are no studies that assess their role in the treatment of chronic poststernotomy pain.172 Spinal cord and peripheral nerve stimulation are alternative minimally invasive options that may be attempted in refractory cases.173-175 CONCLUSIONS

Cardiac surgery most commonly is performed via median sternotomy, which results in significant postoperative pain and

a noninsignificant incidence of chronic pain. Effective pain management after surgery leads to improved patient satisfaction and, possibly, improved clinical outcomes. A number of approaches may be used in the treatment of acute poststernotomy pain, including TEA, spinal anesthesia, intercostal and paravertebral blocks, opioids delivered via intravenous PCA, adjuncts, TENS, patient education, and institution of pain management protocols. It is reasonable to conjecture that an individually tailored multimodal, multidisciplinary approach would yield most desirable outcomes. The use of neuraxial techniques for cardiac surgery remains controversial because of the possibility, albeit rare, of epidural hematoma in the setting of anticoagulation for cardiopulmonary bypass. The pathophysiology of chronic sternotomy pain is poorly understood, but risk factors for its development include poorly controlled postoperative pain and mammary artery graft harvesting. Chronic poststernotomy pain may be treated with medications used in other chronic pain syndromes and with interventional pain procedures, but the evidence for these practices is limited. Future research is needed to elucidate whether chronic sternotomy pain can be prevented by specific intraoperative anesthetic techniques and to discover more effective treatments if it occurs.

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