Pain following cardiac surgery is often related to median sternotomy (peaking during the first 2 postoperative days). Because of problems associated with traditional IV opioid analgesia (nausea and vomiting, pruritus, urinary retention, respiratory depression) and the more recently introduced nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase (COX) inhibitors (gastrointestinal bleeding, renal dysfunction), alternative methods of achieving postoperative analgesia in cardiac surgical patients have been sought. One alternative method is continuous infusion of local anesthetic in the sternotomy incision. In a prospective, randomized, placebo-controlled, double-blind clinical trial, White and associates studied 36 patients undergoing cardiac surgery (30). Intraoperative management was standardized. All patients had two indwelling infusion catheters placed at the median sternotomy incision site at the end of surgery (one in the subfascial plane above the sternum, one above the fascia in the subcutaneous tissue). Patients received either 0.25% bupivacaine (n = 12), 0.5% bupivacaine (n = 12), or normal saline (n = 12) via a constant rate infusion through the catheter (4 mL/hr) for 48 hours following surgery. Average times to tracheal extubation were similar in the three groups (approximately 5–6 hours). Compared with the control group (normal saline), there was a statistically significant reduction in verbal rating scale pain scores and IV patient-controlled morphine analgesia use in the 0.5% bupivacaine group. Patient satisfaction with their pain management was also improved in the 0.5% bupivacaine group versus saline control. However, there were no significant differences in patient-controlled morphine analgesia use between the 0.25% bupivacaine and control groups. Although tracheal extubation time and the duration of the intensive care unit stay (30 hours versus 34 hours, respectively) were not significantly altered, time to ambulation (1 day versus 2 days, respectively) and duration of hospital stay (4.2 days versus 5.7 days, respectively) were lower in the 0.5% bupivacaine group than in the control group. Serum bupivacaine concentrations in patients were reasonable. One complication related to the local anesthetic delivery system was encountered when a catheter tip was inadvertently broken off during its removal from the incision site, which required surgical reexploration of the wound under local anesthesia. The authors conclude that continuous infusion of 0.5% bupivacaine at 4 mL/hour is effective for decreasing postoperative pain and the need for postoperative supplemental opioid analgesic medication, as well as for improving patient satisfaction (earlier ambulation, reduced length of hospital stay) with pain management after cardiac surgery.

Another published clinical investigation reveals the potential benefits of using a continuous infusion of local anesthetic combined with intercostal nerve blocks in patients following cardiac surgery (31). In this prospective, randomized, placebo-controlled, double-blind clinical trial, Dowling and associates studied 35 healthy patients undergoing cardiac surgery (31). Patients undergoing elective CABG via median sternotomy were randomized to either ropivacaine or placebo groups. At the end of the operation, prior to wound closure, bilateral intercostal nerve injections from T1 to T12 were performed using 20 mL of either 0.2% ropivacaine or normal saline. After sternal reapproximation with wires, two catheters with multiple side openings were placed anterior to the sternum (Fig. 22-1). Infusions of 0.2% ropivacaine or normal saline at approximately 4 mL/hour for 48 hours were delivered through these catheters. Both groups exhibited similar postoperative extubation times (approximately 8 hours). Total mean patient-controlled morphine analgesia consumption during the immediate postoperative period (72 hours) was significantly decreased in the ropivacaine group when compared with the placebo group (47.3 mg versus 78.7 mg, respectively, p = 0.038). Mean overall pain scores (0–10 scale) were also significantly decreased in the ropivacaine group when compared with the placebo group (1.6 versus 2.6, respectively, p = 0.005). Most interestingly, patients receiving ropivacaine had a significantly shorter length of stay of 5.2 days ± 1.3 days compared with 8.2 days ± 7.9 days for patients receiving normal saline (p = 0.001). One patient in the placebo group had an extremely long postoperative hospitalization (39 days). However, the difference between the two groups regarding length of hospital stay remained statistically significant even if this outlier was removed (5.2 days ± 1.3 days versus 6.3 days ± 2.8 days, respectively, p <0.01). Despite differences in postoperative analgesia, postoperative pulmonary function (assessed via forced expiratory volume in 1 second and peak expiratory flow) was similar between the two groups. There was no difference in wound infections or wound healing between the two groups during hospitalization or after hospital discharge. No complications related to placement of the sternal wound catheters or performance of the intercostal nerve blocks were encountered. The significant decrease in hospital length of stay observed by the investigators is intriguing, may result in substantial cost reductions, and deserves further study.

The management of postoperative pain with continuous direct infusion of local anesthetic into the surgical wound has
been described following a wide variety of surgeries other than cardiac (inguinal hernia repair, upper abdominal surgery, laparoscopic nephrectomy, cholecystectomy, knee arthroplasty, shoulder surgery, and gynecologic operative laparoscopy) (32). The infusion pump systems used for anesthetic wound perfusion are regulated by the U.S. Food and Drug Administration (FDA) as medical devices. Thus, adverse events reported to the FDA include tissue necrosis, surgical wound infection, and cellulitis following orthopedic, gastrointestinal, podiatric, and other surgeries. None of these reported adverse events as of yet have involved patients undergoing cardiac surgery. The most commonly reported complication is tissue necrosis, an adverse event almost never seen following normal surgical procedures. Furthermore, consequences of these reported adverse events were typically severe and required intervention and additional medical and/or surgical treatment. Although these initial reports may be isolated incidents, they may also represent an early warning that is representative of a widespread problem. Nevertheless, these reports provide a potentially important signal, suggesting the need for further investigation into the relationship between use of these infusion pumps for direct continuous infusion of local anesthetics and other drugs into surgical wounds and the effect on tissue necrosis, serious infections, or cellulitis. Neither of the two clinical investigations involving local anesthetic infusion in patients following cardiac surgery with median sternotomy report such wound complications (30,31). Regardless, these safety issues merit careful consideration because of the importance of sternal wound complications in this setting.

With the increasing popularity of minimally invasive cardiac surgery, which utilizes non sternotomy incisions (minithoracotomy), the use of nerve blocks in cardiac surgical patients has increased as well (33,34,35,36,37,38). Thoracotomy incisions (transverse anterolateral minithoracotomy, vertical anterolateral minithoracotomy), owing to trauma of the costal cartilage tissue, damage to ribs, tissue damage to muscles, and tissue damage to peripheral nerves, may induce more intense postoperative pain than median sternotomy. Adequate analgesia following thoracotomy is important because pain is a key component in alteration of lung function following thoracic surgery. Uncontrolled pain causes a reduction in respiratory mechanics, reduced mobility, and increases in hormonal and metabolic activity. Perioperative deterioration in respiratory mechanics may lead to pulmonary complications and hypoxemia, which may in turn lead to myocardial ischemia/infarction, cerebrovascular accidents, thromboembolism, and/or delayed wound healing, further leading to increased morbidity and prolonged hospital stay. Various analgesic techniques have been developed to treat postoperative thoracotomy pain. The most commonly utilized techniques include intercostal nerve blocks, intrapleural administration of local anesthetics, and thoracic paravertebral blocks.

Intercostal nerve block has been used extensively for analgesia following thoracic surgery (33,35). Intercostal nerve blocks can be performed either intraoperatively or postoperatively and usually provide sufficient analgesia lasting approximately 6 to 12 hours (depending on amount and type of local anesthetic utilized); these blocks may need to be repeated if additional analgesia is required. Local anesthetics may be administered as a single treatment under direction vision, before chest closure; as a single preoperative percutaneous injection; as multiple percutaneous serial injections; or via an indwelling intercostal catheter. Blockade of intercostal nerves interrupts C-fiber afferent transmission of impulses to the spinal cord. A single intercostal injection of a long-acting local anesthetic can provide pain relief and improve pulmonary function in patients following thoracic surgery for up to 6 hours. To achieve longer duration of analgesia, a continuous extrapleural intercostal nerve block technique may be used in which a catheter is placed percutaneously into an extrapleural pocket by the surgeon. A continuous intercostal catheter allows frequent dosing or infusions of local anesthetic agents and avoids multiple needle injections. Various clinical studies have confirmed the analgesic efficacy of this technique, and the technique compares favorably with thoracic epidural analgesic techniques (33). A major concern associated with intercostal nerve block is the potentially high amount of local anesthetic systemic absorption, yet multiple clinical studies involving patients undergoing thoracic surgery have documented safe blood levels with standard techniques. Clinical investigations involving patients undergoing thoracic surgery indicate that intercostal nerve blockade by intermittent or continuous infusion of 0.25% to 0.5% bupivacaine with epinephrine is an effective method for supplementing systemic IV opioid analgesia for postthoracotomy pain. The value of single preclosure injections remains doubtful.

Intrapleural administration of local anesthetics initiates analgesia via mechanisms that remain incompletely understood (33,35). However, the mechanism of action of extrapleural regional anesthesia seems to depend primarily on diffusion of the local anesthetic into the paravertebral region. Local anesthetic agents then affect not only the ventral nerve root but also afferent fibers of the posterior primary ramus. Posterior ligaments of the posterior primary ramus innervate posterior spinal muscles and skin and are traumatized during posterolateral thoracotomy. Intrapleural administration of local anesthetic agent to this region through a catheter inserted in the extrapleural space thus creates an anesthetic region in the skin. The depth and width of the anesthetic region depends on diffusion of the local anesthetic agent in the extrapleural space. With this technique, local anesthetics may be administered via an indwelling intrapleural catheter placed between the parietal and visceral pleura by intermittent or continuous infusion regimens. Systemic absorption of local anesthetic and toxicity are always a concern with this technique, but have not been substantiated in clinical studies that assayed plasma levels (33,35). A handful of clinical investigations involving patients undergoing thoracic surgery via thoracotomy incision suggest that 0.25% to 0.5% bupivacaine may improve analgesia in patients following thoracic surgery, yet its true efficacy as a postoperative analgesic in this patient population remains somewhat controversial (36). The analgesic benefits are of short duration, and there does not appear to be a significant overall opioid-sparing effect. Furthermore, the optimum concentration and duration remains to be defined. However, a recently published prospective, randomized clinical study involving 50 patients undergoing minimally invasive direct CABG (via minithoracotomy) reported that an intrapleural analgesic technique (using 0.25% bupivacaine) is safe and effective and compares favorably to a conventional thoracic epidural technique (37). However, careful catheter positioning, chest tube clamping, and anchoring of the catheter are mandatory for postoperative intrapleural analgesia to be effective. A major factor implicated in lack of efficacy regarding intrapleural techniques is loss of local anesthetic solution through intercostal chest drainage tubes. Although clamping the chest tubes during the postoperative period will increase analgesic efficacy, it may not be safe to clamp chest tubes, as they provide important drainage of hemorrhage and air and allow for enhanced lung patency and expansion.
Apart from proper catheter positioning (insertion of catheter under direct vision and anchoring catheter to skin is essential), effective analgesia with this technique also appears to depend on whether surgery to the lung was performed or whether the pleural anatomy and physiology are relatively intact.

Thoracic paravertebral block involves injection of local anesthetic adjacent to the thoracic vertebrae, close to where the spinal nerves emerge from the intervertebral foramina (Fig. 22-2 and see Figs. 16-4, and 16-15,16-16,16-17). Thoracic paravertebral block, when compared to thoracic epidural analgesic techniques, provides equivalent analgesia, is technically easier, and may harbor less risk. Several different techniques exist for successful thoracic paravertebral block, and have recently been extensively reviewed (34) (Chapter 16). These blocks may be effective in alleviating acute and chronic pain of unilateral origin from the chest and/or abdomen. Unilateral paravertebral block is useful for attaining postthoracotomy analgesia, because pain following lateral thoracotomy is essentially always unilateral. The benefits of unilateral paravertebral blockade are a lesser incidence of adverse events (hypotension, urinary retention) and a decreased risk of systemic local anesthetic toxicity because less local anesthetic is used. The clinical investigations involving unilateral paravertebral block in patients undergoing thoracic surgery are few (33,35). Therefore, it is not possible to determine from the available literature whether the technique of paravertebral blockade (single injection) is truly useful in the postoperative analgesic management of patients following thoracotomy. Continuous thoracic paravertebral infusion of local anesthetic, placed under direct vision at thoracotomy or using a loss-of-resistance technique, is an effective method of providing analgesia following thoracotomy. Indeed, continuous thoracic paravertebral block, as part of a balanced analgesic regimen, may provide effective pain relief with very few side effects following thoracotomy and appears to be comparable to thoracic epidural analgesia (34). Bilateral use of thoracic paravertebral block has been described.

In summary, intercostal nerve blocks, intrapleural administration of local anesthetics, and thoracic paravertebral block offer the advantages of simplicity and efficacy in controlling postoperative pain in patients undergoing thoracic incisions for cardiac surgery. However, although the analgesic efficacy of these techniques sometimes is comparable to intrathecal techniques and epidural techniques, these techniques appear to work best as a part of a multimodal analgesic regimen. The patient must be observed for complications associated with infiltrations of large quantities of local anesthetic when utilizing these analgesic techniques.

Intrathecal and/or epidural techniques, utilizing opioids and/or local anesthetics, initiate reliable postoperative analgesia in patients following cardiac surgery (39). Additional potential advantages of using intrathecal and/or epidural techniques in patients undergoing cardiac surgery include stress response attenuation and thoracic cardiac sympathectomy. Intrathecal or epidural anesthesia and analgesia (with local anesthetics or opioids) can effectively inhibit the stress response associated with surgical procedures (27). Local anesthetics appear to possess greater efficacy than opioids in perioperative stress response attenuation, perhaps because of their unique mechanism of action. Although still a matter of some debate, perioperative stress response attenuation with epidural local anesthetics and/or opioids in high-risk patients after major noncardiac surgery may potentially decrease morbidity and mortality (7,8,27). Unfortunately, to achieve perioperative stress response attenuation in patients undergoing cardiac surgery using IV opioids in this manner does not allow tracheal extubation to occur in the immediate postoperative period. Intrathecal or epidural anesthesia and analgesia techniques (particularly with local anesthetics) are attractive alternatives because of their potential to attenuate the perioperative stress response yet still allow tracheal extubation to occur in the immediate postoperative period.

The myocardium and coronary vasculature are densely innervated by sympathetic nerve fibers that arise from T1 to T5 and profoundly influence total coronary blood flow and distribution (40). Cardiac sympathetic nerve activation initiates coronary artery vasoconstriction (41) and paradoxical coronary vasoconstriction in response to intrinsic vasodilators (42). In patients with coronary artery disease, cardiac sympathetic
nerve activation disrupts the normal matching of coronary blood flow and myocardial oxygen demand (43,44). Animal models have revealed an intense poststenotic coronary vasoconstrictive mechanism mediated by cardiac sympathetic nerve activation that attenuates local metabolic coronary vasodilation in response to myocardial ischemia (45,46). Furthermore, myocardial ischemia initiates a cardiocardiac reflex mediated by sympathetic nerve fibers, which augments the ischemic process (47). Cardiac sympathetic nerve activation likely plays a central role in initiating postoperative myocardial ischemia by decreasing myocardial oxygen supply via these mechanisms (27,48).

Thoracic epidural anesthesia with local anesthetics effectively blocks cardiac sympathetic nerve afferent and efferent fibers, whereas epidural opioids are unable to effectively block such cardiac sympathetic nerve activity (27). Patients with symptomatic coronary artery disease benefit clinically from cardiac sympathectomy; the application of thoracic sympathetic blockade in the management of angina pectoris was described as early as 1965 (49). Thoracic epidural anesthesia with local anesthetics increases the diameter of stenotic epicardial coronary artery segments without causing dilation of coronary arterioles (43), decreases determinants of myocardial oxygen demand (44), improves left ventricular function (50), and decreases anginal symptoms (44,51). Furthermore, cardiac sympathectomy increases the endocardial-to-epicardial blood flow ratio (52,53), beneficially affects collateral blood flow during myocardial ischemia (53), decreases poststenotic coronary vasoconstriction (46), and attenuates the myocardial ischemia-induced cardiocardiac reflex (46). In an animal model, thoracic epidural anesthesia with local anesthetics actually decreased myocardial infarct size following coronary artery occlusion (52). Of note, these beneficial effects are not caused by systemic absorption of the local anesthetic (52). In short, thoracic epidural anesthesia with local anesthetics may benefit patients undergoing cardiac surgery by effectively blocking cardiac sympathetic nerve activity and improving the myocardial oxygen supply-demand balance.

Application of intrathecal analgesia to patients undergoing cardiac surgery was initially reported by Mathews and Abrams in 1980 (54). They described the administration of intrathecal morphine (1.5–4.0 mg) to 40 adults after the induction of general anesthesia for cardiac surgery. Somewhat remarkably, all 40 patients awakened pain-free at the end of surgery (prior to leaving the operating room) and 36 patients were tracheally extubated prior to transfer to the intensive are unit. Postoperatively, all 40 patients were entirely pain-free for the first 27.5 postoperative hours, and 17 did not require any supplemental analgesics prior to discharge from the hospital. Mathews and Abrams summarize: “The benefits of recovering from surgery free from pain have been impressive. This has been particularly appreciated by patients who have had previous operations with conventional anaesthesia and postoperative analgesic drugs. The patients have been remarkably comfortable, able to move more easily in bed, and more cooperative, thus greatly helping their nursing care” (54). After this impressive clinical display, other investigators have subsequently applied intrathecal anesthesia and analgesia techniques to patients undergoing cardiac surgery (55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83). Most clinical investigators have used intrathecal morphine to provide prolonged postoperative analgesia, although some clinical investigators have used intrathecal fentanyl, sufentanil, and/or local anesthetics. A recently published anonymous survey of members of the Society of Cardiovascular Anesthesiologists indicates that almost 8% of practicing anesthesiologists incorporate intrathecal techniques into their anesthetic management of adults undergoing cardiac surgery (83). Of these anesthesiologists, 75% practice in the United States, 72% perform the intrathecal injection prior to induction of anesthesia, 97% utilize morphine, 13% utilize fentanyl, 2% utilize sufentanil, 10% utilize lidocaine, and 3% utilize tetracaine (83).

Two randomized, blinded, placebo-controlled clinical studies revealed the ability of intrathecal morphine to induce significant postoperative analgesia following cardiac surgery (69,76). In 1988, Vanstrum and associates prospectively randomized 30 patients to receive either intrathecal morphine (0.5 mg) or intrathecal placebo prior to induction of anesthesia (76). Intraoperative anesthetic management was standardized, and all patients postoperatively received exclusively IV morphine administered by a nurse who attempted to keep the linear analog pain score at less than four (1–10 scale). Although pain scores between groups were not significantly different at any postoperative time interval tested, patients who received intrathecal morphine required significantly less IV morphine than placebo controls (2.4 mg versus 8.3 mg, respectively, p <0.02) during the initial 30 hours following intrathecal injection. Associated with this enhanced analgesia in patients receiving intrathecal morphine was a substantially decreased need for antihypertensive medications (sodium nitroprusside, nitroglycerine, hydralazine) during the immediate postoperative period. Time to tracheal extubation (approximately 20 hours) and postoperative arterial blood gas tensions following anesthesia were not significantly affected by the use of intrathecal morphine. In 1996, Chaney and associates prospectively randomized 60 patients to receive either intrathecal morphine (4.0 mg) or intrathecal placebo prior to induction of anesthesia for elective CABG (69). Intraoperative anesthetic management was standardized and, after tracheal extubation, all patients received exclusively IV morphine via patient-controlled analgesia (PCA). The mean time from intensive care unit arrival to tracheal extubation was similar in all patients (approximately 20 hours). However, patients who received intrathecal morphine required significantly less IV morphine than placebo controls (33.2 mg versus 51.1 mg, respectively, p <0.05) during the initial postoperative period. Despite enhanced analgesia, no clinical differences between groups existed regarding postoperative morbidity (pruritus, nausea, vomiting, urinary retention, prolonged somnolence, atrial fibrillation, ventricular tachycardia, myocardial infarction, cerebral infarction), mortality, nor duration of postoperative hospital stay (approximately 9 days in each group).

The mid 1990s saw the emergence of fast-track cardiac surgery, with the goal being tracheal extubation in the immediate postoperative period. Chaney and associates, in 1997, were the first to study the potential clinical benefits of intrathecal morphine when used in patients undergoing cardiac surgery and early tracheal extubation (68). They prospectively randomized 40 patients to receive either intrathecal morphine (10 μg/kg) or intrathecal placebo prior to induction of anesthesia for elective CABG. Intraoperative anesthetic management was standardized (IV fentanyl, 20 μg/kg, and IV midazolam, 10 mg) and all patients postoperatively received exclusively IV morphine via PCA. Of the patients who were tracheally extubated during the immediate postoperative period, the mean
time from intensive care unit arrival to tracheal extubation was significantly prolonged in those who received intrathecal morphine (10.9 hours ± 4.4 hours; p = 0.02) when compared to placebo controls (7.6 hours ± 2.5 hours). Three patients who received intrathecal morphine had tracheal extubation substantially delayed (12–24 hours) because of prolonged ventilatory depression, likely secondary to intrathecal morphine. No clinical differences existed between groups regarding IV morphine use for 48 hours, postoperative morbidity, mortality, nor duration of postoperative hospital stay (approximately 9 days in each group).

These somewhat discouraging findings (absence of enhanced analgesia, prolongation of tracheal extubation time) stimulated the same group of investigators, in 1999, to repeat the study, but decrease intraoperative IV fentanyl administration to 10 μg/kg (66). Of the patients tracheally extubated during the immediate postoperative period, mean time to tracheal extubation was similar in patients who received intrathecal morphine (6.8 hours ± 2.8 hours) when compared to intrathecal placebo patients (6.5 hours ± 3.2 hours). However, once again, four (10%) patients who received intrathecal morphine had tracheal extubation substantially delayed (14 hours, 14 hours, 18 hours, 19 hours) because of prolonged respiratory depression (likely secondary to intrathecal morphine). No clinical differences existed between groups regarding postoperative morbidity, mortality, nor duration of postoperative hospital stay (approximately 6 days in each group). Based on these three prospective, randomized, double-blind, placebo-controlled clinical investigations, the authors concluded that, although intrathecal morphine certainly can initiate reliable postoperative analgesia, its use in the setting of fast-track cardiac surgery and early tracheal extubation may be detrimental by potentially delaying tracheal extubation in the immediate postoperative period.

Since this time, however, other clinical investigators have revealed that certain combinations of intraoperative anesthetic technique, coupled with appropriate doses of intrathecal morphine, will allow both tracheal extubation following cardiac surgery within the immediate postoperative period along with enhanced analgesia (58). Importantly, limiting the amounts of intraoperative IV opioids and IV sedatives and the application of a postoperative tracheal extubation protocol may be more important in achieving the goal of early tracheal extubation following cardiac surgery than adequate pain control during the immediate postoperative period.

Many other suboptimally designed clinical investigations attest to the ability of intrathecal morphine to induce substantial postoperative analgesia in patients following cardiac surgery (Table 22-2). Intrathecal doses of 0.5 to 10.0 mg administered prior to cardiopulmonary bypass initiate reliable postoperative analgesia, the quality of which depends not only on the intrathecal dose administered but also on the type and amount of IV analgesics and sedatives used for the intraoperative baseline anesthetic. The optimal dose of intrathecal morphine for achieving the maximum postoperative analgesia with minimum undesirable drug effects is uncertain. Naturally, when larger doses of intrathecal morphine are used, more intense and prolonged postoperative analgesia is purchased at the expense of more undesirable side effects, including nausea and vomiting, pruritus, urinary retention, and respiratory depression.

Because of morphine’s low lipid solubility, analgesic effects following intrathecal injection are delayed. Thus, even large doses of intrathecal morphine administered to patients prior to cardiac surgery will not initiate reliable intraoperative analgesia (76,77,78,81) and therefore would not be expected to potentially attenuate the intraoperative stress response associated with cardiopulmonary bypass. Only an extremely large dose of intrathecal morphine (10.0 mg) may initiate reliable intraoperative analgesia (80). A single clinical investigation has examined the ability of intrathecal morphine to potentially attenuate the intraoperative stress response associated with cardiopulmonary bypass as measured by blood catecholamine levels (69). In this clinical investigation by Chaney and associates, patients were prospectively randomized to receive either intrathecal morphine (4.0 mg) or intrathecal placebo prior to induction of anesthesia for elective CABG with cardiopulmonary bypass. Intraoperative anesthetic management was standardized, and multiple arterial blood samples were obtained perioperatively to ascertain norepinephrine and epinephrine levels. Patients who were administered intrathecal morphine experienced similar perioperative increases in blood catecholamine levels when compared with placebo controls. Thus, it appears that intrathecal morphine (even in relatively large doses) is unable to reliably attenuate the perioperative stress response associated with cardiac surgery and cardiopulmonary bypass.

However, although unable to reliably attenuate the perioperative stress response associated with cardiopulmonary bypass, intrathecal morphine (by initiating postoperative analgesia) may potentially attenuate the stress response during the immediate postoperative period (76). Vanstrum and associates revealed that patients who were administered 0.5 mg of intrathecal morphine prior to the induction of anesthesia not only required significantly less IV morphine postoperatively when compared to placebo controls but also required significantly less IV nitroprusside (58.1 mg versus 89.1 mg, respectively, p <0.05) during the initial 24 postoperative hours to control hypertension, suggesting partial postoperative stress response attenuation.

Intrathecal fentanyl, sufentanil, and/or local anesthetics have been used in patients undergoing cardiac surgery, hoping to provide intraoperative anesthesia and analgesia (and stress response attenuation), with mixed results (Table 22-2). Intrathecal sufentanil (50 μg), administered prior to the induction of anesthesia for cardiac surgery can reduce volatile anesthetic requirements during mediastinal dissection but is unable to reliably block intraoperative hemodynamic responses to laryngoscopy and intubation (73).

Administration of intrathecal local anesthetics to patients after the induction of anesthesia for cardiac surgery may help promote intraoperative hemodynamic stability (70,72).

In 1994, in a retrospective review, 18 adult patients were administered lumbar intrathecal hyperbaric bupivacaine (23–30 mg) and/or hyperbaric lidocaine (150 mg) mixed with morphine (0.5–1.0 mg) following the induction of anesthesia (72). In an attempt to produce a “total spinal” and, thus, thoracic cardiac sympathectomy, the Trendelenburg position was maintained for at least 10 minutes following intrathecal injection. Heart rate decreased significantly (baseline mean 67 bpm to postinjection mean 52 bpm) after the intrathecal injection (indicating cardiac sympathectomy was obtained) and not a single patient exhibited ECG evidence of myocardial ischemia prior to cardiopulmonary bypass. Although these authors report that

the technique provided stable perioperative hemodynamics, 17 of 18 patients required IV phenylephrine at some time intraoperatively to increase blood pressure. In 1996, the same group of investigators reported similar hemodynamic changes in a case report involving a 10-year-old child with Kawasaki disease who underwent CABG and receiving intrathecal hyperbaric bupivacaine mixed with morphine via a lumbar puncture following induction of anesthesia (70).

A recently published, small (n = 38 patients), prospective, randomized, blinded clinical investigation reveals that large doses of intrathecal bupivacaine (37.5 mg) administered to patients immediately prior to induction of general anesthesia (19 patients received intrathecal bupivacaine, 19 patients served as controls) for elective CABG may potentially initiate intraoperative stress response attenuation (assessed via serum mediator levels, hemodynamics, and qualitative/quantitative alterations in myocardial β-receptors) (84). However, no effect on real clinical outcome parameters (i.e., tracheal extubation times, respiratory function, perioperative spirometry) was observed. Mean tracheal extubation times (measured from the time of sternotomy dressing application) were extremely short in both groups (11–19 minutes). Postoperative pain scores and morphine use via PCA did not differ between the two groups. Not surprisingly, phenylephrine use was more common in patients who received intrathecal bupivacaine when compared to control patients.

In summary, the many clinical investigations involving the use of intrathecal analgesic techniques in patients undergoing cardiac surgery indicate that the administration of intrathecal morphine to patients prior to cardiopulmonary bypass initiates reliable postoperative analgesia following cardiac surgery. Intrathecal opioids or local anesthetics cannot reliably attenuate the perioperative stress response associated with cardiopulmonary bypass that persists during the immediate postoperative period. Although intrathecal local anesthetics (not opioids) may induce perioperative thoracic cardiac sympathectomy, the hemodynamic changes associated with a “total spinal” makes the technique unsuitable for patients with cardiac disease.

Thoracic epidural anesthesia and analgesia with local anesthetics and/or opioids induces significant postoperative analgesia in patients undergoing cardiac procedures. A recently published anonymous survey of members of the Society of Cardiovascular Anesthesiologists indicates that 7% of practicing anesthesiologists incorporate thoracic epidural techniques into their anesthetic management of adults undergoing cardiac surgery (83). Of these anesthesiologists, 58% practice in the United States. Regarding the timing of epidural instrumentation, 40% perform instrumentation before induction of general anesthesia, 12% perform instrumentation following induction of general anesthesia, 33% perform instrumentation at the end of surgery, and 15% perform instrumentation on the first postoperative day (83).

The initial description of thoracic epidural anesthesia and analgesia applied to a cardiac surgical patient occurred in 1954 (85). Clowes and associates describe their presurgical anesthetic technique in a 55-year-old man with severe cardiac failure: “An endotracheal tube was passed with topical anesthesia. Under extradural block of the upper thorax, hypotension developed but responded to the administration of a vasopressor drug. At this time the patient became comatose” (Fig. 22-3) (85). The patient eventually expired. Application of thoracic epidural anesthesia and analgesia to patients undergoing cardiac surgery during the modern surgical era was initially reported by Hoar and associates in 1976 (86). They described the intraoperative insertion of thoracic epidural catheters in 12 patients following CABG (after IV protamine, prior to transfer to intensive care unit). The epidural catheters were injected with lidocaine and bupivacaine during the immediate postoperative period to promote analgesia and effectively control hypertension. Administration of epidural local anesthetics to these patients significantly decreased postoperative blood pressure in hypertensive and normotensive patients; not a single patient required cardiac or peripheral vascular stimulants during the immediate postoperative study period.

The 1987 report by El-Baz and Goldin was the first to describe the insertion of thoracic epidural catheters in patients prior to cardiac surgery and also involved epidural opioids, rather than local anesthetics (87). In prospective, randomized fashion, patients undergoing elective CABG received either routine treatment for postoperative pain (n = 30 patients, IV morphine) or a continuous infusion of morphine (0.1 mg/hr) via a thoracic epidural catheter (n = 30 patients). Thoracic epidural catheters were inserted at T3–T4 immediately prior to induction of anesthesia on the day of surgery. Intraoperative anesthetic technique was standardized; mean postoperative tracheal extubation time was significantly shorter in patients receiving thoracic epidural anesthesia when compared to control patients (9 ± 3 hours versus 18 ± 5 hours, respectively, p <0.01). Continuous thoracic epidural infusion of morphine also achieved better postoperative pain relief in patients than IV morphine (significantly better pain scores, significantly less supplemental IV morphine). Furthermore, in a subgroup of 20 patients (10 per group), postoperative “stress” was assessed via serum cortisol and β-endorphin levels. Patients receiving thoracic epidural anesthesia had significantly lower postoperative levels of these mediators when compared to control patients, indicating potential postoperative stress response attenuation. Continuous thoracic epidural infusion of morphine (when compared to controls) was also associated with a lower incidence of opioid-related side effects during the immediate postoperative period. The insertion of the thoracic epidural catheter immediately prior to systemic heparin administration was not associated with any neurologic problems.

Since this initial report of potential benefits (reliable postoperative analgesia, stress response attenuation, facilitation of early tracheal extubation), others clinical investigators have subsequently applied thoracic epidural anesthesia and analgesia to patients undergoing cardiac surgery (88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109,110,111,112,113,114,115,116,117,118,119,120,121,122,123) (Table 22-3). For example, patients randomized to receive intermittent boluses of thoracic epidural infusion intraoperatively, followed by continuous infusion postoperatively, exhibited significantly decreased blood levels of norepinephrine and epinephrine (98,101) and cortisol (98) perioperatively when compared with patients managed similarly without thoracic epidural catheters (101). Furthermore, increased blood catecholamine levels in these patients were associated with increased systemic vascular resistance (101). Continuous thoracic epidural bupivacaine and sufentanil infusion administered perioperatively significantly decreased blood levels of norepinephrine following sternotomy when compared to conventional analgesic methods (104). Other clinical studies further attest to the ability of thoracic epidural anesthesia with


local anesthetics to promote perioperative hemodynamic stability in patients undergoing cardiac surgery, which suggests perioperative stress response attenuation (86,100,101,104).