Anesthesia & Analgesia:
Cardiovascular Anesthesia: Review Article
Intrathecal and Epidural Anesthesia and Analgesia for Cardiac Surgery
Chaney, Mark A. MD
Department of Anesthesia and Critical Care, University of Chicago, Illinois
Accepted for publication August 3, 2005.
Address correspondence and reprint requests to Mark A. Chaney, MD, Department of Anesthesia and Critical Care, University of Chicago, 5841 South Maryland Ave., MC-4028, Chicago, IL 60637. Address e-mail to email@example.com.
Adequate postoperative analgesia prevents unnecessary patient discomfort. It may also decrease morbidity, postoperative hospital length of stay and, thus, cost. Achieving optimal pain relief after cardiac surgery is often difficult. Many techniques are available, and all have specific advantages and disadvantages. Intrathecal and epidural techniques clearly produce reliable analgesia in patients undergoing cardiac surgery. Additional potential benefits include stress response attenuation and thoracic cardiac sympathectomy. The quality of analgesia obtained with thoracic epidural anesthetic techniques is sufficient to allow cardiac surgery to be performed in awake patients without general endotracheal anesthesia. However, applying regional anesthetic techniques to patients undergoing cardiac surgery is not without risk. Side effects of local anesthetics (hypotension) and opioids (pruritus, nausea/vomiting, urinary retention, and respiratory depression), when used in this manner, may complicate perioperative management. Increased risk of hematoma formation in this scenario has generated much of lively debate regarding the acceptable risk-benefit ratio of applying regional anesthetic techniques to patients undergoing cardiac surgery.
Adequate postoperative analgesia prevents unnecessary patient discomfort. It may also decrease morbidity, postoperative hospital length of stay and, thus, cost. Because postoperative pain management has been considered important, the American Society of Anesthesiologists has published practice guidelines regarding this topic (1). Furthermore, in recognition of the need for improved pain management, the Joint Commission on Accreditation of Healthcare Organizations has developed standards for the assessment and management of pain in accredited hospitals and other health care settings (2). Patient satisfaction (no doubt linked to adequacy of postoperative analgesia) has become an essential element that influences the clinical activity not only of anesthesiologists, but also of all health care professionals.
Achieving optimal pain relief after cardiac surgery is often difficult. Pain may be associated with many interventions, including sternotomy, thoracotomy, leg vein harvesting, pericardiotomy, or chest tube insertion, among others. Inadequate analgesia during the postoperative period may increase morbidity by causing adverse hemodynamic, metabolic, immunologic, and hemostatic alterations (3–5). Thus, aggressive control of postoperative pain may improve outcome in high-risk patients after noncardiac surgery (6,7), as well as in cardiac surgery (8,9). Postoperative analgesia may be attained via a wide variety of techniques (Table 1). Traditionally, analgesia after cardiac surgery has been obtained with IV opioids. However, IV opioid use is associated with definite detrimental side effects, and longer-acting opioids may delay tracheal extubation during the immediate postoperative period. In the current era of early extubation (fast-tracking) and minimally invasive surgical techniques (including off-pump surgery), cardiac anesthesiologists are exploring unique analgesic options other than traditional IV opioids for control of postoperative pain in patients after cardiac surgery (10,11). During the last decade, intrathecal and epidural techniques have been used more often in response to this changing surgical climate.
Pain and Cardiac Surgery
Surgical or traumatic injury initiates changes in the peripheral and central nervous system that must be addressed therapeutically to promote analgesia. The potential clinical benefits of attenuating the perioperative surgical stress response (above and beyond simply attaining adequate clinical analgesia) have received much attention, and it remains fairly controversial (12). However, it is clear that inadequate postoperative analgesia, or an uninhibited perioperative surgical stress response, has the potential to initiate pathophysiologic changes in all major organ systems, which may lead to substantial postoperative morbidity.
Pain after cardiac surgery may be intense. It may originate from many sources, including the incision, intraoperative tissue retraction and dissection, vascular cannulation sites, vein harvesting sites, and chest tubes, among others (13,14). Patients in whom an internal mammary artery is surgically exposed may have substantially more postoperative pain (15). One prospective clinical investigation, involving 200 consecutive patients undergoing cardiac surgery via median sternotomy, assessed the location, distribution, and intensity of postoperative pain (13). Pain location, distribution, and intensity were documented in the morning on the first, second, third, and seventh postoperative days using a standardized picture dividing the body into 32 anatomic areas. These investigators found that pain intensity was highest on the first postoperative day and least on the third postoperative day. Pain distribution did not vary throughout the postoperative period, yet location did. As time from operation increased, pain moved from primarily incisional/epigastric to osteoarticular. Another common source of postoperative pain in patients after cardiac surgery is thoracic cage rib fractures (16,17). Age also impacts pain intensity; patients younger than 60 years experience more intense pain than older patients. Whereas maximal pain intensity after cardiac surgery is usually only graded as “moderate,” there is ample room for clinical improvement in analgesic control to minimize pain intensity, especially during the first few postoperative days.
Persistent pain after cardiac surgery, while rare, can be problematic (18–20). The cause of persistent pain after sternotomy is multifactorial. Tissue destruction, intercostal nerve trauma, scar formation, rib fractures, sternal infection, stainless steel wire sutures, and costochondral separation may all play roles. Younger patients are thought to be at higher risk for developing chronic, long-lasting pain. The correlation of severity of acute postoperative pain and development of chronic pain syndromes has been suggested. Ho et al. (18) assessed, via survey, 244 patients after cardiac surgery and median sternotomy and found that persistent pain (defined as pain still present 2 or more months after surgery) was reported in almost 30% of patients. However, such persistent pain was usually reported as mild, with only 7% of patients reporting interference with daily living. The temporal nature of this pain was reported as being mostly brief/transient and periodic/intermittent. Twenty patients (8%) also described symptoms of numbness, burning pain, and tenderness over the internal mammary artery harvesting site, which are symptoms suggestive of internal mammary artery syndrome. Thus, mild persistent pain after cardiac surgery and median sternotomy is common yet only infrequently substantially interferes with daily life.
Whereas the most common source of pain in patients after cardiac surgery is the chest wall, leg pain from vein graft harvesting can be problematic as well. Such pain may not become apparent until the late postoperative period, which may be related to the progression of patient mobilization and the decreasing impact of incisional pain (unmasking leg incisional pain). The recent use of minimally invasive vein graft harvesting techniques (endoscopic vein graft harvesting) decreases postoperative leg pain intensity and duration when compared with conventional open techniques (21).
Patient satisfaction is as much related to the comparison between anticipated and experienced pain as it is to the actual level of pain experienced. Satisfaction is achieved when a situation is better than expected and dissatisfaction when one is worse than expected. Patients undergoing cardiac surgery are very concerned regarding postoperative pain and tend to preoperatively expect more intense postoperative pain than that actually experienced (14). Because of these unique preoperative expectations, patients after cardiac surgery who receive only moderate analgesia after surgery will likely still be satisfied with their pain control. Thus, patients may experience pain of moderate intensity after cardiac surgery yet still express very high satisfaction levels (14,15).
Potential Clinical Benefits of Adequate Postoperative Analgesia
Inadequate analgesia (linked to an uninhibited stress response) during the postoperative period may lead to many adverse hemodynamic (tachycardia, hypertension, and vasoconstriction), metabolic (increased catabolism), immunologic (impaired immune response), and hemostatic (platelet activation) alterations. In patients undergoing cardiac surgery, perioperative myocardial ischemia is most often observed during the immediate postoperative period and seems to be related to outcome (22,23). Intraoperatively, initiation of cardiopulmonary bypass (CPB) causes substantial increases in stress response hormones (norepinephrine, epinephrine, etc.) that persist into the immediate postoperative period and may contribute (along with inadequate analgesia) to myocardial ischemia during this time (24–26). Furthermore, postoperative myocardial ischemia may be aggravated by cardiac sympathetic nerve activation, which disrupts the balance between coronary blood flow and myocardial oxygen demand (27). Thus, during the pivotal immediate postoperative period after cardiac surgery, adequate analgesia (coupled with stress response attenuation) may potentially decrease morbidity and enhance health-related quality of life (27,28).
There is evidence indicating that aggressive control of postoperative pain in patients after noncardiac surgery may beneficially affect outcome (6,7). There is also evidence that aggressive control of postoperative pain in patients after cardiac surgery may beneficially affect outcome (8,9). Mangano et al. (8) prospectively randomized 106 adults undergoing elective coronary artery bypass grafting (CABG) to receive either standard postoperative analgesia or intensive analgesia during the immediate postoperative period. Standard care patients received small-dose intermittent IV morphine for the first 18 postoperative h, whereas intensive analgesia patients received a continuous IV sufentanil infusion during the same time period. Patients receiving sufentanil demonstrated less severe myocardial ischemia episodes (detected by continuous electrocardiographic monitoring) during the immediate postoperative period. The authors postulate that the administration of intensive analgesia during the immediate postoperative period may have suppressed the sympathetic nervous system activation more completely, thereby having numerous beneficial clinical effects, including beneficial alterations in sensitivity of platelets to epinephrine, beneficial alterations in fibrinolysis, enhanced regional left ventricular function, and decreased coronary artery vasoconstriction—all potentially leading to a reduced incidence and severity of myocardial ischemia. Anand and Hickey (9) prospectively randomized 45 neonates undergoing elective cardiac surgery (mixed procedures) to receive either standard perioperative care or deep-opioid anesthesia. Standard care patients received a halothane/ketamine/morphine anesthetic with intermittent IV morphine for the first 24 postoperative h, whereas deep-opioid patients received an IV sufentanil anesthetic with a continuous infusion of either IV fentanyl or IV sufentanil during the same postoperative time period. Neonates receiving continuous postoperative opioid infusions demonstrated a reduced perioperative stress response (assessed via multiple blood mediators), less perioperative morbidity (hyperglycemia, lactic acidemia, sepsis, metabolic acidosis, and disseminated intravascular coagulation), and had significantly fewer deaths than the control group. The accompanying editorial accurately summarizes this clinical investigation: “What Anand and Hickey have shown is that this reluctance to treat pain adequately is not a necessary evil. It markedly contributes to a bad outcome” (29).
Techniques Available for Postoperative Analgesia
Whereas the mechanisms of postoperative pain and the pharmacology of analgesic drugs are relatively well understood, the delivery of effective postoperative analgesia remains far from universal. Many techniques are available (Table 1). All of the techniques listed in Table 1 have advantages and disadvantages (risks and benefits). Postoperative local anesthetic infiltration via indwelling infusion catheters placed at the median sternotomy incision site at the end of surgery seems promising (enhanced analgesia, early ambulation, and reduced hospital length of stay), yet questions regarding safety persist (tissue necrosis and infection). Nerve blocks (intercostal, intrapleural, and paravertebral) offer simplicity, yet efficacy remains an issue (work best supplementing other analgesic techniques). IV opioids form the cornerstone of postcardiac surgery analgesia (used for many years with excellent results). However, IV opioids may cause pruritus, nausea and vomiting, urinary retention, and respiratory depression. Whereas patient-controlled analgesic techniques offer potential unique benefits (reliable analgesic effect, improved patient autonomy, flexible adjustment to individual needs, etc.), whether or not they truly offer significant clinical advantages (when compared with traditional nurse-administered analgesic techniques) to patients immediately after cardiac surgery remains to be determined. Nonsteroidal antiinflammatory drugs (NSAIDS) and cyclooxygenase (COX) inhibitors were initially promising, yet serious questions persist regarding safety (alterations in gastric mucosal barrier and renal tubular function, inhibition of platelet aggregation, sternal wound infection, and thromboembolic complications). Alpha-adrenergic-agonists may enhance postoperative analgesia and hemodynamic stability (potentially decreasing myocardial ischemia) yet may cause excessive postoperative sedation and aggravate postoperative hemodynamic instability via bradycardia or decreased systemic vascular resistance. The American Society of Anesthesiologists Task Force on Acute Pain Management in the Perioperative Setting reports that administration of two analgesic medications that act by different mechanisms (multimodal analgesia) provide superior analgesic efficacy with equivalent or reduced adverse effects. Two routes of administration, when compared with a single route, may be more effective in providing perioperative analgesia.
Intrathecal and Epidural Techniques
It is clear that intrathecal and epidural techniques produce reliable postoperative analgesia in patients after cardiac surgery (30). Additional potential advantages of using these techniques in this scenario include stress response attenuation and thoracic cardiac sympathectomy.
Intrathecal or epidural techniques may inhibit the stress response associated with surgical procedures (27). Local anesthetics are more effective than opioids in stress response attenuation, perhaps because of their unique mechanism of action. Although still a matter of debate, perioperative stress response attenuation with epidural local anesthetics or opioids in high-risk patients after major noncardiac surgery may potentially improve outcome (6,7,27). In patients undergoing cardiac surgery, initiation of CPB causes significant increases in stress response hormones that persist into the immediate postoperative period (24–26). Attenuation of this component of the stress response with postoperative continuous IV infusion of opioids may also decrease morbidity and mortality in these patients (8,9). Intrathecal and epidural techniques (particularly with local anesthetics) are attractive alternatives to IV opioids in cardiac surgery patients for 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 T1-5 and profoundly influence total coronary blood flow and distribution (31). Cardiac sympathetic nerve activation initiates coronary artery vasoconstriction (32) and paradoxical coronary vasoconstriction in response to intrinsic vasodilators (33). In patients with coronary artery disease, cardiac sympathetic nerve activation disrupts the normal matching of coronary blood flow and myocardial oxygen demand (34,35). 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 (36,37). Furthermore, myocardial ischemia initiates a cardio-cardiac reflex mediated by sympathetic nerve fibers, which augments the ischemic process (38). Cardiac sympathetic nerve activation likely plays a central role in initiating postoperative myocardial ischemia by decreasing myocardial oxygen supply via the mechanisms listed previously (27,39). Thoracic epidural anesthesia with local anesthetics effectively blocks cardiac sympathetic nerve afferent and efferent fibers (27). Opioids, administered similarly, are unable to effectively block such cardiac sympathetic nerve activity (27). Patients with symptomatic coronary artery disease benefit clinically from cardiac sympathectomy, and the application of thoracic sympathetic blockade in the management of angina pectoris was described as early as 1965 (40). Thoracic epidural anesthesia with local anesthetics increases the diameter of stenotic epicardial coronary artery segments without causing dilation of coronary arterioles (34), decreases determinants of myocardial oxygen demand (35), improves left ventricular function (41), and decreases anginal symptoms (35,42). Furthermore, cardiac sympathectomy increases the endocardial-to-epicardial blood flow ratio (43,44), beneficially affects collateral blood flow during myocardial ischemia (44), decreases poststenotic coronary vasoconstriction (37), and attenuates the myocardial ischemia-induced cardio-cardiac reflex (37). In an animal model, thoracic epidural anesthesia with local anesthetics actually decreased myocardial infarct size after coronary artery occlusion (43). Thus, thoracic epidural techniques 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 (45) in 1980. Other investigators have subsequently applied intrathecal techniques to patients undergoing cardiac surgery (46–66). Most investigators have used intrathecal morphine in hopes of providing prolonged postoperative analgesia. Some investigators have used intrathecal fentanyl, sufentanil, or local anesthetics for intraoperative anesthesia (with stress response attenuation) or thoracic cardiac sympathectomy. 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 (67).
Two early randomized, blind, placebo-controlled clinical studies reveal the ability of intrathecal morphine to induce significant postoperative analgesia after cardiac surgery (55,61). Vanstrum et al. (61) prospectively randomized 30 patients to receive either intrathecal morphine (0.5 mg) or intrathecal placebo before the induction of anesthesia. Patients who received intrathecal morphine required significantly less IV morphine than placebo controls during the initial 30 h after intrathecal injection. Associated with this enhanced analgesia was a substantially decreased need for antihypertensive medications during the immediate postoperative period. Time to tracheal extubation (approximately 20 h) and postoperative arterial blood gas tensions were not significantly affected. Chaney et al. (55) prospectively randomized 60 patients to receive either intrathecal morphine (4.0 mg) or intrathecal placebo before the induction of anesthesia for elective CABG. The mean time from intensive care unit (ICU) arrival to tracheal extubation was similar in all patients (approximately 20 h). However, patients who received intrathecal morphine required significantly less IV morphine than placebo controls during the initial postoperative period. Despite enhanced analgesia, there were no clinical differences between groups regarding postoperative morbidity, mortality, or duration of postoperative hospital stay.
The mid-1990s saw the emergence of fast-track cardiac surgery, with the goal being tracheal extubation in the immediate postoperative period. Chaney et al. (54), 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. They prospectively randomized 40 patients to receive either intrathecal morphine (10 mcg/kg) or intrathecal placebo before the induction of anesthesia for elective CABG. Of the patients who were tracheally extubated during the immediate postoperative period, the mean time from ICU arrival to tracheal extubation was significantly prolonged in patients who received intrathecal morphine (10.9 h) when compared with placebo controls (7.6 h). Three patients who received intrathecal morphine had tracheal extubation substantially delayed (12–24 h) because of prolonged ventilatory depression. Although the mean postoperative IV morphine use for 48 h was less in patients who received intrathecal morphine when compared with patients who received intrathecal placebo, the difference between groups was not statistically significant. There were no clinical differences between groups regarding postoperative morbidity, mortality, or duration of postoperative hospital stay.
These somewhat discouraging findings stimulated the same group of investigators to try again, this time decreasing the amount of intraoperative IV fentanyl patients received (52). Forty patients were prospectively randomized to receive either intrathecal morphine (10 mcg/kg) or intrathecal placebo before the induction of anesthesia for elective CABG. 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 h) when compared with intrathecal placebo patients (6.5 h). However, four patients who received intrathecal morphine had tracheal extubation substantially delayed because of prolonged respiratory depression. The mean postoperative IV morphine use during the immediate postoperative period was actually larger in patients receiving intrathecal morphine when compared with patients receiving intrathecal placebo, yet the difference between groups was not statistically significant. There were no clinical differences between groups regarding postoperative morbidity, mortality, or duration of postoperative hospital stay. Thus, Chaney et al. (54) concluded from their 3 prospective, randomized, double-blind, placebo-controlled clinical investigations in the late 1990s involving 140 healthy adults undergoing elective CABG that although intrathecal morphine can produce reliable postoperative analgesia (yet no additional benefits), 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. Additional clinical studies performed by other investigators have also suggested the potential of intrathecal morphine to hinder early tracheal extubation (68).
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 after cardiac surgery within the immediate postoperative period along with enhanced analgesia. Alhashemi et al. (47) prospectively randomized 50 adults undergoing elective CABG to receive either 1 of 2 doses of intrathecal morphine (250 mcg or 500 mcg) or intrathecal placebo. Tracheal extubation times were similar in the placebo group, 250 mcg intrathecal morphine group, and 500 mcg intrathecal morphine group (approximately 6 h). However, postoperative morphine requirements in the placebo group (21.3 mg), 250 mcg intrathecal morphine group (13.6 mg), and 500 mcg intrathecal morphine group (11.7 mg) were substantially different. However, despite enhanced analgesia, there were no differences among the study groups in regards to midazolam, nitroglycerin, and sodium nitroprusside requirements in the postoperative period. Nonetheless, postextubation blood gas tension analysis, use of supplemental inspired oxygen, and ICU length of stay were similar among the three groups. These investigators reveal that the use of intrathecal morphine in patients undergoing fast-track cardiac surgery and early tracheal extubation may (if used appropriately) provide enhanced postoperative analgesia without delaying tracheal extubation. However, no additional clinical benefits, beyond analgesia, are obtained.
One group of investigators has recently examined the use of intrathecal morphine in patients after off-pump CABG (69). In this retrospective chart review, 112 patients received preinduction intrathecal morphine (range, 5–24 mcg/kg) as part of routine anesthetic care for off-pump CABG. Seventy-eight percent were tracheally extubated in the operating room (one patient required immediate reintubation secondary to agitation). Whereas no patient was reintubated during the immediate postoperative period for hypoventilation, 4% (5 patients) required naloxone to treat respiratory depression or somnolence (2 required continuous infusions in the ICU). Furthermore, 30% experienced minor opioid-related sequelae (pruritus, nausea, and vomiting). The investigators recommend that when using intrathecal morphine in this setting, continuous respiratory monitoring should be available during the immediate postoperative period to detect delayed respiratory depression.
Many other suboptimally designed clinical investigations (retrospective, observational, etc.) attest to the ability of intrathecal morphine to produce substantial postoperative analgesia in patients after cardiac surgery (Table 2), the quality of which depends not only on the intrathecal dose administered, but also on the type and amount of IV drugs used for the intraoperative baseline anesthetic. However, no additional clinical benefits, beyond analgesia, have been reliably obtained. 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 produced at the expense of more undesirable drug effects.
Intrathecal clonidine has been shown to provide profound analgesia in patients after noncardiac surgery. Clonidine also reduces sympathetic activity and arterial blood pressure, making it an attractive single drug that potentially provides analgesia and blunts the hypertensive response. Lena et al. (70) were the first to examine the use of intrathecal clonidine in patients undergoing cardiac surgery. They prospectively randomized 45 patients into 3 groups. One group received intrathecal morphine (4 mcg/kg), and one group received intrathecal morphine (4 mcg/kg) and intrathecal clonidine (1 mcg/kg) before the anesthesia induction. The third group received no intrathecal injection and served as the control group. Postoperative analgesia was significantly better in patients receiving intrathecal morphine and clonidine when compared with the other two groups. Mean time to tracheal extubation was also shorter in the intrathecal morphine and clonidine group when compared with the intrathecal morphine group and control group (225 min, 293 min, and 330 min, respectively). None of these patients experienced postoperative hypotension or excessive sedation. These findings indicate that combining intrathecal clonidine and morphine may provide better postoperative analgesia than intrathecal morphine alone and allows early tracheal extubation after cardiac surgery.
Because of morphine’s low lipid solubility, analgesic effects after intrathecal injection are delayed. Only an extremely large dose of intrathecal morphine (10.0 mg) may initiate reliable intraoperative analgesia in this setting (71). Only a few investigations have examined the ability of intrathecal morphine to potentially attenuate the intraoperative stress response associated with CPB as measured by blood catecholamine levels. Chaney et al. (55) prospectively randomized patients to receive either intrathecal morphine (4.0 mg) or intrathecal placebo before the induction of anesthesia for elective cardiac surgery with CPB. Multiple arterial blood samples were perioperatively obtained 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. Another small investigation revealed that intrathecal morphine (1.0 mg or 1.5 mg) was unable to attenuate the stress response associated with cardiac surgery, as assessed via perioperative plasma levels of cortisol, epinephrine, norepinephrine, and dopamine (72). Thus, it seems that intrathecal morphine (even in relatively large doses) is unable to reliably attenuate the perioperative stress response associated with cardiac surgery and CPB.
Most clinical attempts at inducing thoracic cardiac sympathectomy in patients undergoing cardiac surgery have used thoracic epidural anesthesia with local anesthetics. However, some have attempted cardiac sympathectomy in this setting with an intrathecal injection of local anesthetic. Reviewed retrospectively, 18 adult patients were administered lumbar intrathecal hyperbaric bupivacaine (23–30 mg), hyperbaric lidocaine (150 mg), or both, mixed with morphine (0.5–1.0 mg) after the induction of anesthesia (58). In an attempt to produce a “total spinal” and, thus, thoracic cardiac sympathectomy, the Trendelenburg position was maintained for at least 10 min after the intrathecal injection. Heart rate decreased significantly (baseline mean, 67 bpm, to postinjection mean, 52 bpm) after the intrathecal injection (indicating that cardiac sympathectomy was obtained). Seventeen of the 18 patients required IV phenylephrine at some time during surgery to increase arterial blood pressure. Whereas these investigators report that the patients experienced enhanced postoperative analgesia, definite conclusions cannot be reached regarding this technique because of study design (small retrospective review).
One small clinical investigation reveals that large doses of intrathecal bupivacaine (37.5 mg) administered to patients immediately before the induction of general anesthesia for elective CABG may potentially initiate intraoperative stress response attenuation (assessed via serum mediator levels, hemodynamics, and qualitative/quantitative alterations in myocardial β-receptors) (73). However, no real effect on clinical outcome variables (tracheal extubation times, respiratory function, perioperative spirometry, etc.) was observed. Postoperative pain scores and morphine use were not beneficially affected, and phenylephrine use was common in patients who received intrathecal bupivacaine.
In summary, the many clinical investigations involving intrathecal techniques in patients undergoing cardiac surgery indicate that the administration of intrathecal morphine to patients produces reliable postoperative analgesia after cardiac surgery. However, no additional clinical benefits, beyond analgesia, have been reliably obtained. Intrathecal techniques cannot reliably attenuate the perioperative stress response associated with cardiac surgery that persists during the immediate postoperative period. Although intrathecal local anesthetics may induce thoracic cardiac sympathectomy, the hemodynamic changes associated with a total spinal makes the technique unacceptable in patients with cardiac disease.
The initial description of thoracic epidural anesthesia and analgesia applied to cardiac surgical patients occurred in 1954 (74). Application of thoracic epidural techniques to patients undergoing cardiac surgery during the modern surgical era was initially reported by Hoar et al. (75) in 1976. They described the use of thoracic epidural catheters during the immediate postoperative period to promote analgesia and effectively control hypertension. The 1987 report by El-Baz and Goldin (76) was the first to describe the insertion of thoracic epidural catheters in patients before performance of cardiac surgery. Since this time, other clinical investigators have subsequently applied thoracic epidural techniques to patients undergoing cardiac surgery (77–109). Most investigators have used thoracic epidural local anesthetics in hopes of providing analgesia, stress response attenuation, or thoracic cardiac sympathectomy. Some investigators have used thoracic epidural opioids to provide intraoperative and postoperative analgesia. An 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 (67).
Thoracic epidural techniques with local anesthetics or opioids produce significant postoperative analgesia in patients after cardiac surgery. Patients randomized to receive a continuous thoracic epidural morphine infusion after cardiac surgery required significantly less postoperative supplemental IV morphine when compared with patients without thoracic epidural catheters (5 mg/d versus 18 mg/d per patient, respectively) during the initial 3 postoperative days (76). Children randomized to receive caudal epidural morphine during surgery after cardiac surgery required significantly less postoperative supplemental IV morphine when compared with patients who did not receive epidural morphine (0.32 mg/kg versus 0.71 mg/kg, respectively) during the initial 24 postoperative h (92). These are just two of the numerous clinical studies that attest to the ability of thoracic epidural techniques with local anesthetics and opioids to induce substantial postoperative analgesia in patients after cardiac surgery (Table 3).
One unique clinical investigation directly compared a thoracic epidural technique to IV clonidine in patients undergoing cardiac surgery (80). Loick et al. (80) prospectively randomized 70 patients undergoing elective CABG to receive either perioperative thoracic epidural supplementation (bupivacaine or sufentanil continuous infusion) to general anesthesia, to receive perioperative IV clonidine supplementation (continuous infusion) to general anesthesia, or to receive only general anesthesia (controls). Hemodynamics, plasma epinephrine and norepinephrine levels, plasma cortisol levels, troponin T levels, and other plasma cardiac enzymes were perioperatively assessed. Both the thoracic epidural and IV clonidine groups experienced postoperative decreases in heart rate compared with the control group. Effects on stress response mediators were unpredictable and variable. Electrocardiographic evidence of ischemia occurred in 70% of control patients, 50% of thoracic epidural patients, and 40% of IV clonidine patients. The release of troponin T was attenuated (when compared with controls) in the thoracic epidural group only (no effect in the IV clonidine group). Interestingly, the highest quality of postoperative analgesia was found in the patients receiving IV clonidine. Postoperative comfort scores (rated between excellent and good) did not differ among the three groups.
Many clinical investigations have proven that thoracic epidural techniques with local anesthetics significantly attenuate the stress response in patients undergoing cardiac surgery. However, it remains controversial whether or not such stress response attenuation truly affects outcome. Patients randomized to receive intermittent boluses of thoracic epidural bupivacaine during surgery followed by a continuous infusion after surgery exhibited significantly decreased blood levels of norepinephrine and epinephrine when compared with patients managed similarly without thoracic epidural catheters (87). Furthermore, increased blood catecholamine levels in these patients were associated with increased systemic vascular resistance (87). Patients randomized to receive continuous thoracic epidural bupivacaine infusion exhibit significantly decreased blood levels of norepinephrine and cortisol when compared with patients managed similarly without thoracic epidural catheters (84). Patients randomized to receive a continuous thoracic epidural bupivacaine and sufentanil infusion exhibited significantly decreased blood levels of norepinephrine after sternotomy when compared with patients managed similarly without thoracic epidural catheters (89). Numerous studies further attest to the ability of thoracic epidural techniques with local anesthetics to promote hemodynamic stability in patients undergoing cardiac surgery, which suggests perioperative stress response attenuation (75,86,87,89).
Two provocative studies demonstrate the ability of thoracic epidural techniques to produce thoracic cardiac sympathectomy in patients undergoing cardiac surgery (85,86). In the first study, patients undergoing CABG were evaluated with reverse thermodilution catheters inserted into the coronary sinus before the induction of anesthesia (85). Patients randomized to receive intermittent boluses of thoracic epidural bupivacaine during surgery followed by a continuous infusion after surgery exhibited significant decreases in coronary vascular resistance post-CPB when compared with pre-CPB values, whereas patients managed similarly without thoracic epidural catheters exhibited significant increases in coronary vascular resistance post-CPB. In the second study, patients undergoing CABG were evaluated with similar catheters that had been inserted into the coronary sinus before the induction of anesthesia (86). Patients randomized to receive a single bolus of thoracic epidural mepivacaine immediately after the induction of anesthesia exhibited significantly decreased cardiac norepinephrine spillover after sternotomy when compared with patients managed similarly without thoracic epidural catheters. Furthermore, 20% of patients managed without thoracic epidural catheters exhibited electrocardiographic evidence of myocardial ischemia after sternotomy, whereas no patient managed with a thoracic epidural catheter exhibited myocardial ischemia during this time.
Perioperative cardiac sympathectomy induced via thoracic epidural techniques with local anesthetics may clinically benefit patients undergoing cardiac surgery by increasing myocardial oxygen supply (34,43,44). Cardiac sympathectomy may also offer additional benefits to patients undergoing cardiac surgery. Clinical studies demonstrate that thoracic epidural techniques with local anesthetics significantly decrease heart rate before (89) and after (84,89) the initiation of CPB and significantly decrease the need to administer β-adrenergic blockers after CPB (87). Clinical studies also demonstrate that thoracic epidural techniques with local anesthetics significantly decrease systemic vascular resistance before (86,87) and after (89,93) the initiation of CPB. Patients undergoing cardiac surgery who receive thoracic epidural local anesthetics may also exhibit significant decreases in postoperative electrocardiographic evidence of myocardial ischemia (89). However, it remains controversial whether such cardiac sympathectomy truly affects outcome.
A relatively large clinical investigation highlights the potential clinical benefits of thoracic epidural techniques (along with difficulties determining clinical relevance of such studies) in cardiac surgical patients (78). Scott et al. (78) prospectively randomized (nonblinded) 420 patients undergoing elective CABG to receive either thoracic epidural bupivacaine/clonidine and general anesthesia or general anesthesia alone (control group). In thoracic epidural patients, the epidural infusion was continued for 96 h after surgery (titrated according to need). In the control patients, target-controlled infusion alfentanil was used for the first 24 postoperative h and then followed by patient-controlled analgesia with morphine for the next 48 h. After surgery, striking clinical differences were observed between the two groups. Postoperative supraventricular arrhythmia, respiratory tract infection, renal failure, and acute confusion were all significantly decreased in thoracic epidural patients when compared with control patients. However, data from this investigation must be viewed with caution. The clinical protocol dictated that β-adrenergic blocker therapy could not be used during or after surgery for the 5 days of the study period (except in those patients who developed a new arrhythmia requiring additional therapy). Because approximately 90% of this study’s patients were taking β-adrenergic blockers before surgery, this unique perioperative management clouds interpretation of postoperative supraventricular arrhythmia data. Also, despite prospective randomization, substantially fewer patients receiving thoracic epidural catheters were active smokers before surgery when compared with controls, which clouds interpretation of postoperative respiratory tract infection data. These investigators also found that postoperative preextubation maximal expiratory lung volumes were increased in thoracic epidural patients (when compared with controls), and postoperative tracheal extubation was facilitated in these patients, as well (yet thoracic epidural patients and control patients were managed somewhat differently during the immediate postoperative period). Postoperative analgesia was not definitively assessed in this clinical investigation. Although the results of this clinical investigation are certainly intriguing, definitive conclusions regarding the use of thoracic epidural techniques in patients undergoing cardiac surgery cannot be drawn because of the study’s substantial limitations, highlighted by an accompanying Editorial (109) and three subsequent Letters to the Editor (110–112).
In contrast to the somewhat encouraging findings of Scott et al., two prospective, randomized, nonblinded investigations reveal that using thoracic epidural techniques in patients undergoing cardiac surgery may not offer substantial clinical benefits (113,114). Priestly et al. (114) prospectively randomized 100 patients undergoing elective CABG to receive either thoracic epidural ropivacaine/fentanyl and general anesthesia or general anesthesia alone (control group). Postoperatively, thoracic epidural patients received epidural ropivacaine/fentanyl for 48 h (supplemental analgesics available if required), whereas control patients received nurse-administered IV morphine, followed by patient-controlled analgesia morphine. Thoracic epidural patients were tracheally extubated sooner than controls (3.2 h versus 6.7 h, respectively), yet this difference may have been secondary to the different amounts of intraoperative IV opioid administered to the 2 groups. Postoperative pain scores at rest were significantly lower in thoracic epidural patients only on postoperative Days 0 and 1 (equivalent on Days 2 and 3). Postoperative pain scores during coughing were significantly lower in thoracic epidural patients only on postoperative Day 0 (equivalent on Days 1, 2, and 3). There were no significant differences between the two groups in postoperative oxygen saturation on room air, chest radiograph changes, or spirometry. Furthermore, no clinical differences were detected between the two groups regarding postoperative mobilization goals, atrial fibrillation, postoperative hospital discharge eligibility, or actual postoperative hospital discharge. In short, this investigation revealed that a thoracic epidural may provide enhanced postoperative analgesia (although brief) and enhance early postoperative tracheal extubation yet has no effect on important clinical variables (morbidity, hospital length of stay, etc.). Royse et al. (113) prospectively randomized 80 patients undergoing elective CABG to receive either thoracic epidural ropivacaine/fentanyl and general anesthesia or general anesthesia alone (control group). Postoperatively, thoracic epidural patients received epidural ropivacaine/fentanyl until the third postoperative day, whereas control patients received nurse-administered IV morphine, followed by patient-controlled analgesia morphine. Thoracic epidural patients were tracheally extubated earlier during the immediate postoperative period than controls (2.6 h versus 5.4 h, respectively), yet this difference may have been secondary to the different amount of intraoperative IV anesthetics administered. Postoperative pain scores at rest and with cough were significantly less in thoracic epidural patients on postoperative Days 1 and 2 only (equivalent on postoperative Day 3). Like the Priestley et al. investigation, there were no substantial differences between the two groups regarding important postoperative clinical variables (respiratory function, renal function, atrial fibrillation, ICU length of stay, and hospital length of stay).
Despite enhanced postoperative analgesia offered via thoracic epidural techniques, such analgesia does not seem to decrease the incidence of persistent pain after cardiac surgery. Ho et al. (18) assessed via survey 244 patients after cardiac surgery via median sternotomy. One-hundred-fifty patients received perioperative supplementation of general anesthesia with thoracic epidural ropivacaine/fentanyl infusion, and 94 patients received general anesthesia and routine postoperative nurse-controlled IV morphine (along with intraoperative wound infiltration with ropivacaine at chest wall closure). Persistent pain (defined as pain still present 2 or more mo after surgery) was similar in the two cohorts (reported in almost 30% of patients). However, persistent pain reported by these patients was mild in most cases, infrequently interfering with daily life.
The quality of analgesia obtained with thoracic epidural anesthetic techniques is sufficient to allow cardiac surgery to be performed in awake patients without general endotracheal anesthesia. The initial report of awake cardiac surgery was published in 2000 (115). Karagoz et al. (115) describe the perioperative course of five patients who underwent elective off-pump single-vessel CABG via minithoracotomy with only thoracic epidural techniques (spontaneous ventilation throughout). All five patients did well, and none had to be converted to general endotracheal anesthesia. Soon thereafter, a group of investigators described the perioperative course of 12 patients who underwent elective off-pump multivessel CABG via complete sternotomy with only thoracic epidural techniques (116). All patients did well, yet two required conversion to general endotracheal anesthesia (one for incomplete analgesia and one for pneumothorax). Soon, investigators revealed that outpatient CABG was possible (discharge to home within 24 h of hospital admission) in a small (n = 20) group of patients undergoing cardiac surgery solely via thoracic epidural techniques (117). Since these initial small clinical reports have appeared, larger series of patients have been published, proving that awake cardiac surgery (without CPB) is feasible and potentially safe (118–128). In 2003, the first case report of awake cardiac surgery requiring CPB was published (129). In this astonishing case report from Austria, a 70-year-old man with aortic stenosis underwent aortic valve replacement with assist of normothermic CPB (total time 123 min; cross-clamp time 82 min) solely via the thoracic epidural technique. Verbal communication with the patient was possible on demand throughout CPB. The patient did well and experienced an unremarkable postoperative course.
In summary, the many clinical investigations involving the use of epidural techniques in patients undergoing cardiac surgery indicate that administration of thoracic epidural opioids or local anesthetics to patients before and after CPB produce reliable postoperative analgesia after cardiac surgery. However, no additional clinical benefits, beyond analgesia, have been reliably obtained. Administration of thoracic epidural local anesthetics can both reliably attenuate the perioperative stress response associated with cardiac surgery and induce thoracic cardiac sympathectomy (yet it remains controversial whether or not they truly affect outcome). Enhanced postoperative analgesia has the potential to facilitate early tracheal extubation, yet one may safely reach this goal without assistance of thoracic epidural techniques (130).
A recently published meta-analysis by Liu et al. (131) assessed effects of perioperative central neuraxial techniques on outcome after coronary artery bypass surgery. These authors, via MEDLINE and other databases, searched for randomized controlled trials of patients undergoing coronary artery bypass surgery with CPB. Fifteen trials enrolling 1178 patients were included for thoracic epidural analysis, and 17 trials enrolling 668 patients were included for intrathecal analysis. Thoracic epidural techniques did not affect incidences of mortality or myocardial infarction yet seemed to reduce the risk of dysrhythmias (atrial fibrillation and tachycardia), pulmonary complications (pneumonia and atelectasis), the time to tracheal extubation, and analog pain scores. Intrathecal techniques did not affect incidences of mortality, myocardial infarction, dysrhythmias, or time to tracheal extubation and seemed only to modestly decrease systemic morphine use and pain scores (while increasing the incidence of pruritus). These authors conclude that central neuraxial techniques do not affect rates of mortality or myocardial infarction after CABG yet may be associated with improvements in faster time to tracheal extubation, decreased pulmonary complications and cardiac dysrhythmias, and reduced pain scores. However, the authors also note that most potential clinical benefits offered by these techniques (earlier extubation, decreased dysrhythmias, and enhanced analgesia) may be achieved in other ways, such as using fast-track protocols, use of β-adrenergic blockers or amiodarone, and use of NSAIDs or COX-2 inhibitors.
Whether intrathecal and epidural techniques truly affect morbidity and mortality in patients undergoing cardiac surgery remains to be determined. All clinical reports involving the use of intrathecal and thoracic epidural techniques for cardiac surgery involve small numbers of patients, and few (if any) are well designed (Tables 2 and 3). Only a handful of clinical studies involving intrathecal techniques are prospective, randomized, blinded, and placebo-controlled (Table 2). There are no blinded, placebo-controlled clinical studies involving thoracic epidural techniques in patients undergoing cardiac surgery (Table 3). Furthermore, none of these clinical studies use clinical outcome as a primary end-point. When critically reviewed, this body of literature suggests that these techniques reliably induce enhanced postoperative analgesia yet (at the current time) have no clinically important effect on morbidity and mortality.
Use of intrathecal and epidural techniques in patients undergoing thoracotomy incisions (sometimes used in cardiac surgery) deserves a brief mention (132). Pain after thoracotomy can be intense, which may produce pulmonary complications after surgery. Furthermore, up to half of all patients undergoing thoracotomy incision will develop chronic pain related to the surgical site. Somewhat surprisingly, patients undergoing a clamshell incision (transverse thoracosternotomy) do not experience more postoperative pain than patients undergoing a standard thoracotomy, and lung transplant recipients undergoing thoracotomy have less frequent adequate pain relief than patients undergoing thoracotomy for other indications (133). When compared with standard thoracotomy incisions, patients receiving minithoracotomy incisions experience less postoperative pain and consume less supplemental analgesics during the immediate postoperative period.
There is evidence that indicates that adequate postoperative pain control after thoracotomy may help prevent postoperative pulmonary morbidity and the development of chronic postoperative thoracotomy pain. Therefore, an effective postoperative analgesic plan must be developed for these patients. In contrast to median sternotomy incisions and minithoracotomy incisions, there seems to be clinical evidence that intrathecal and epidural techniques have the potential to decrease postoperative complications after thoracotomy incisions. Specifically, Ballantyne et al. (134) and Licker et al. (135) provide evidence that postoperative pain control with epidural techniques after thoracotomy incision may reduce pulmonary morbidity and overall patient mortality, respectively. However, whereas there is evidence suggesting that thoracic epidural techniques (superiority of thoracic over lumbar routes has been recently called into question) offer superior postoperative analgesia, not all clinical studies have shown that such techniques truly improve postoperative pulmonary function and reduce postoperative pulmonary complications.
Side Effects of Intrathecal and Epidural Local Anesthetics
The most troubling and undesirable drug effect of intrathecal and epidural local anesthetics is hypotension. Spinal anesthesia to upper thoracic dermatomes produces a decrease in mean arterial blood pressure that is accompanied by a parallel decrease in coronary blood flow (136,137). The percentage of arterial blood pressure decrease that is considered acceptable remains speculative, especially in patients with coronary artery disease (138). Furthermore, if α-adrenergic agonists are used to increase arterial blood pressure during this time, there may be detrimental effects (vasoconstriction) on the native coronary arteries and bypass grafts (139,140). Of the few patients who have received intrathecal local anesthetics to produce a total spinal for cardiac surgery, most required IV phenylephrine during surgery to increase arterial blood pressure, indicating that hypotension is a substantial problem with this technique (56,58,73). Hypotension also seems to be relatively common when thoracic epidural local anesthetics are used in this setting. Volume replacement, β-adrenergic agonists, and α-adrenergic agonists are required in a fair proportion of patients, and coronary perfusion pressure may decrease in susceptible patients after CPB.
After epidural administration, local anesthetics can produce blood concentrations of a drug that may initiate detrimental cardiac electrophysiologic effects and myocardial depression (141). In fact, myocardial depression has been detected in patients receiving thoracic epidural anesthesia with bupivacaine, a clinical effect at least partially caused by increased blood concentrations of the drug (142). Concomitant use of β-adrenergic blockers may further decrease myocardial contractility in this setting (143,144). Patients undergoing cardiac surgery who were randomized to receive intermittent boluses of thoracic epidural bupivacaine during surgery followed by a continuous infusion after surgery exhibited significantly increased pulmonary capillary wedge pressures after CPB when compared with patients managed similarly without epidural catheters, which suggests myocardial depression (87).
Thoracic epidural supplementation of general anesthesia in patients undergoing cardiac surgery may produce temporary neurologic deficits in the immediate postoperative period that can complicate management (145). Chakravarthy et al. (145) describe two patients in whom high thoracic epidural local anesthetic supplementation of general anesthesia for off-pump CABG was used. In both patients, focal upper extremity (unilateral) paresis was observed during the immediate postoperative period that resolved after epidural catheter repositioning. The deficits may have been caused by direct nerve irritation from the epidural catheter or unexpected spread of the local anesthetic to the brachial plexus. Whatever the cause, such focal neurologic deficits occurring in patients immediately after cardiac surgery certainly require extra clinical effort to determine the origin.
Two case reports also indicate that epidural techniques may either mask or initiate myocardial ischemia (146,147). Oden and Karagianes (147) describe the perioperative course of a patient who had a history of exertional angina and underwent uneventful cholecystectomy. Postoperatively, analgesia was achieved with continuous lumbar epidural fentanyl. On the second postoperative day, with continuous lumbar epidural fentanyl being administered, ST segment depression was noted on the electrocardiogram. The patient was awake, alert, and did not experience angina. Initiation of IV nitroglycerin resulted in normalization of ischemic electrocardiographic changes. It is possible that epidural fentanyl-induced analgesia masked the patient’s typical anginal pain. Easley et al. (146) describe the perioperative course of a patient with only borderline hypertension who was scheduled for exploratory laparotomy. Before surgery, a low thoracic epidural catheter was inserted, and local anesthetic was administered (sensory level peaked by pinprick at T2). The patient began complaining of left-sided jaw pain, and substantial ST segment depression was noted on the electrocardiogram. Surgery was cancelled, and the patient was treated with aspirin and nitroglycerin. The electrocardiogram normalized yet, based on electrocardiographic changes, troponin levels, and creatine kinase-MB fractions, the patient was diagnosed with a non-Q-wave myocardial infarction. Coronary angiography on the following day was unremarkable, and a presumptive diagnosis of coronary artery spasm was made. It is possible that low thoracic epidural-induced sympathectomy led to alterations in sympathetic-parasympathetic balance (i.e., vasoconstriction above the level of block), leading to coronary artery spasm.
Side Effects of Intrathecal and Epidural Opioids
The four clinically relevant undesirable drug effects of intrathecal and epidural opioids are pruritus, nausea and vomiting, urinary retention, and respiratory depression (148). The most common side effect is pruritus. (Incidence varies widely and is often identified only after direct questioning of patients.) Severe pruritus is rare, occurring in only approximately 1% of patients. The incidence of nausea and vomiting is approximately 30%. Incidence of urinary retention varies widely and occurs most often in young male patients.
The most important undesirable drug effect of intrathecal and epidural opioids is respiratory depression. Only 4 mo after the initial use of intrathecal (149) and epidural (150) opioids in humans, life-threatening respiratory depression was reported (151–153). The incidence of respiratory depression that requires intervention after conventional doses of intrathecal and epidural opioids is approximately 1%, the same as that after conventional doses of IM and IV opioids. Early respiratory depression occurs within minutes of opioid injection and is only associated with administration of intrathecal or epidural fentanyl or sufentanil. Delayed respiratory depression occurs hours after opioid injection and is only associated with administration of intrathecal or epidural morphine. Delayed respiratory depression results from cephalad migration of morphine in cerebrospinal fluid and subsequent stimulation of opioid receptors located in the ventral medulla (154). Factors that increase the risk of respiratory depression include large or repeated doses of opioids, intrathecal use, advanced age, and concomitant use of IV sedatives (148). The magnitude of postoperative respiratory depression is profoundly influenced by the dose of intrathecal or epidural morphine administered and the type and amount of IV drugs used for the intraoperative baseline anesthetic. Prolonged postoperative respiratory depression may delay tracheal extubation, and naloxone may be required in some patients. The optimal dose of intrathecal or epidural morphine in this setting, along with the optimal intraoperative baseline anesthetic that will provide significant postoperative analgesia yet not delay tracheal extubation in the immediate postoperative period, remains to be elucidated.
Risk of Hematoma Formation
Intrathecal or epidural instrumentation entails risk, the most feared complication being hematoma formation. The estimated incidence of hematoma formation is approximately 1:220,000 after intrathecal instrumentation and approximately 1:150,000 after epidural instrumentation (155). Hematoma formation does not occur exclusively during epidural catheter insertion; almost half of all cases develop after catheter removal (155). Although spontaneous hematomas can occur in the absence of intrathecal or epidural instrumentation (156) or during routine instrumentation, most occur when instrumentation is performed in a patient with a coagulopathy (from any cause) or when instrumentation is difficult or traumatic (155). Paradoxically, intrathecal and epidural instrumentation have been performed safely in patients with known clinical coagulopathy (157,158). Risk is certainly increased when intrathecal or epidural instrumentation is performed before systemic heparinization, and hematoma formation has occurred in patients when diagnostic or therapeutic lumbar puncture has been followed by systemic heparinization (159–162). However, by observing certain precautions, intrathecal or epidural instrumentation can be performed safely in patients who will subsequently receive IV heparin (163,164). By delaying surgery 24 h in the event of a traumatic tap, by delaying heparinization 60 min after catheter insertion, and by maintaining tight perioperative control of anticoagulation, more than 4000 intrathecal or epidural catheterizations were performed safely in patients undergoing peripheral vascular surgery who received IV heparin after catheter insertion (164). A retrospective review involving 912 patients further indicates that epidural catheterization before systemic heparinization for peripheral vascular surgery is safe (163). However, the magnitude of anticoagulation in these two studies (activated partial thromboplastin time approximately 100 s) (163) and activated clotting time approximately twice the baseline value (164), involving patients undergoing peripheral vascular surgery, was substantially less than the degree of anticoagulation required in patients undergoing cardiac surgery.
Whereas most investigators agree that the risk of hematoma is increased when intrathecal or epidural instrumentation is performed in a patient before systemic heparinization required for cardiac surgery, the absolute degree of increased risk is somewhat controversial. An extensive mathematical analysis by Ho et al. (165) of the approximately 10,840 intrathecal injections in patients subjected to systemic heparinization required for CPB (without a single episode of hematoma formation) reported in the literature as of the year 2000 estimated that the minimum risk of hematoma formation was 1:220,000, and the maximum risk of hematoma formation was 1:3600 (95% confidence level), yet the maximum risk may be as frequent as 1:2400 (99% confidence level). Similarly, of the approximately 4583 epidural instrumentations in patients subjected to systemic heparinization required for CPB (without a single episode of hematoma formation) reported in the literature as of the year 2000 estimated that the minimum risk of hematoma formation was 1:150,000, and the maximum risk of hematoma formation was 1:1500 (95% confidence level), yet the maximum risk may be as frequent as 1:1000 (99% confidence level) (165). Certain precautions, however, likely decrease risk (155,159). Most clinical studies investigating the use of intrathecal or epidural techniques in patients undergoing cardiac surgery include precautions to decrease risk of hematoma formation. Some use the technique only after demonstration of laboratory evidence of normal coagulation variables, delay surgery 24 h in the event of a traumatic tap, or require that the time from instrumentation to systemic heparinization exceed 60 min. Whereas most studies investigating the use of epidural techniques in patients undergoing cardiac surgery insert catheters the day before scheduled surgery, recent investigators have performed instrumentation on the same day of surgery. The technique should not be used in a patient with known coagulopathy from any cause. Additionally, systemic heparin effect and reversal should be tightly controlled (smallest amount of heparin used for the shortest duration compatible with therapeutic objectives), and patients should be closely monitored after surgery for signs and symptoms of hematoma formation.
In 2004, the first case report was published of an epidural hematoma associated with a thoracic epidural catheter inserted in a patient before cardiac surgery (166). This 18-year-old man had a thoracic (T9-10) epidural catheter uneventfully inserted after the induction of general anesthesia (patient had intense fear of needles) and before the initiation of CPB for aortic valve replacement surgery. Three hours elapsed from instrumentation to systemic heparinization. The entire intraoperative course and immediate postoperative course were uneventful (tracheally extubated soon after surgery and ambulating without difficulty on the first postoperative day). Forty-nine hours after surgery, IV heparin therapy was initiated (prosthetic valve thromboprophylaxis). Fifty-three hours after surgery, alteplase (thrombolytic drug) was used to flush a dysfunctional IV catheter. Within 2 h of IV alteplase administration, the patient reported intense back pain while ambulating. At this point, the epidural catheter was removed. The activated partial thromboplastin time assessed during catheter removal was 87.4 s (normal range, 24.8–37.3 s). The patient was also thrombocytopenic at this time. Upon catheter removal, he experienced sudden onset of numbness and weakness distal to T9. IV heparin was discontinued, and a computed tomographic scan was inconclusive, requiring a magnetic resonance imaging scan, which revealed an epidural hematoma. Five hours from the onset of neurologic symptoms, the patient underwent surgical evacuation of the hematoma (which extended from T8-11). Intraoperatively, IV methylprednisolone was administered, followed by an infusion that was continued for 72 h. Twenty-four hours postlaminectomy, he demonstrated mild residual lower extremity motor and sensory deficits. Six weeks later, his neurological function had returned to normal. Whereas this represents the first published case report of an epidural hematoma associated with a thoracic epidural catheter inserted in a patient before cardiac surgery, this author is aware of at least three additional cases of catastrophic (permanent paralysis) epidural hematoma formation in patients who had thoracic epidural catheters inserted for elective cardiac surgery within the past 5 yr in the United States alone (none published).
Whereas hematoma formation is always a concern, thromboembolic complications may also occur during the postoperative period when normalization of coagulation variables (in a patient requiring anticoagulation) are achieved to safely remove the epidural catheter. Chaney and Labovsky (167) detail such a case. Their case report describes a patient who had a thoracic epidural catheter inserted before elective cardiac surgery. The intraoperative and immediate postoperative courses were uneventful. The patient required postoperative anticoagulation for a mechanical aortic valve and atrial fibrillation. On the seventh postoperative day, coagulation parameters were normalized to safely remove the epidural catheter. On that same day, the patient experienced a left temporal lobe stroke (verified by clinical examination and computed tomographic scan), which gradually resolved over the next 4 days. The increased risk of thromboembolic phenomena in patients requiring anticoagulation via iatrogenic alterations in levels of anticoagulation should thus be considered when applying thoracic epidural techniques in patients undergoing cardiac surgery.
Use of intrathecal and epidural techniques in patients undergoing cardiac surgery, while increasing in popularity, remains extremely controversial, prompting numerous editorials by recognized experts in the field of cardiac anesthesia (168–171). One of the main reasons for such controversy (which likely will continue for some time) is that the numerous clinical investigations regarding this topic are suboptimally designed and use a wide array of disparate techniques, preventing clinically useful conclusions with widespread agreement (172,173). When critically reviewed, the literature suggests that the only clear benefit of using intrathecal or epidural techniques in patients undergoing cardiac surgery is enhanced postoperative analgesia, and they have no clinically important effect on outcome.
Multiple factors are important during the perioperative period that substantially affect outcome and quality of life after cardiac surgery (Table 4) (174). This list of factors in Table 4 is not presented order of importance. Obviously, depending on specific clinical situations, certain factors will be more important than others. It is extremely difficult (if not impossible) to determine the exact importance of attaining adequate postoperative analgesia in relation to all of the factors affecting outcome and quality of life in a patient undergoing cardiac surgery. Furthermore, a clear link between “adequate” or “high-quality” postoperative analgesia and improved outcome in patients after cardiac surgery has yet to be established (175–177). Preemptive analgesia, while intriguing, requires further study to determine its role in affecting postoperative analgesia and outcome (178–181).
However, despite the absence of substantiating scientific evidence, most clinicians intuitively believe that attaining high-quality postoperative analgesia is important because it may prevent adverse physiologic effects that may potentially increase morbidity. Whereas many analgesic techniques are available, IV systemic opioids are the cornerstone of postcardiac surgery analgesia. The potential benefits offered by intrathecal and epidural techniques include intense postoperative analgesia, stress response attenuation, and thoracic cardiac sympathectomy. However, there are clear deficiencies in the literature that prohibit definitive analysis of the risk-benefit ratio of intrathecal and epidural techniques for cardiac surgery. The only clear benefit is enhanced postoperative analgesia, yet the risks associated with these techniques in this setting are real, potentially catastrophic, and beginning to emerge, prompting some to contemplate abandonment of these techniques in cardiac patients (182). Future directions for research should focus on development of well-designed studies with adequate numbers of patients that investigate the potential ability of these techniques to affect morbidity (especially cardiac and pulmonary) and mortality in patients after cardiac surgery. Only after such studies are performed will a definitive analysis of the risk-benefit ratio of intrathecal and epidural anesthesia for cardiac surgery be possible.
1. American Society of Anesthesiologists Task Force on Acute Pain Management. Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management. Anesthesiology 2004;100:1573–81.
2. Joint Commission on Accreditation of Healthcare Organization. Pain assessment and management: an organizational approach. 2000. Available at: http://www.jcaho.org
3. Weissman C. The metabolic response to stress: an overview and update. Anesthesiology 1990;73:308–27.
4. Kehlet H. Surgical stress: the role of pain and analgesia. Br J Anaesth 1989;63:189–95.
5. Roizen MF. Should we all have a sympathectomy at birth or at least preoperatively? Anesthesiology 1988;68:482–4.
6. Tuman KJ, McCarthy RJ, March RJ, et al. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 1991;73:696–704.
7. Yeager MP, Glass DD, Neff RK, Brinck-Johnsen T. Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 1987;66:729–36.
8. Mangano DT, Siliciano D, Hollenberg M, et al. Postoperative myocardial ischemia: therapeutic trials using intensive analgesia following surgery. Anesthesiology 1992;76:342–53.
9. Anand KJS, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med 1992;326:1–9.
10. Wallace AW. Is it time to get on the fast track or stay on the slow track? Anesthesiology 2003;99:774.
11. Myles PS, Daly DJ, Djaiani G, et al. A systematic review of the safety and effectiveness of fast-track cardiac anesthesia. Anesthesiology 2003;99:982–7.
12. Royston D, Kovesi T, Marczin N. The unwanted response to cardiac surgery: time for a reappraisal? J Thorac Cardiovasc Surg 2003:125:32–5.
13. Mueller XM, Tinguely F, Tevaearai HT, et al. Pain location, distribution, and intensity after cardiac surgery. Chest 2000;118:391–6.
14. Nay PG, Elliott SM, Harrop-Griffiths AW. Postoperative pain. expectation and experience after coronary artery bypass grafting. Anaesthesia 1996;51:741–3.
15. Meehan DA, McRae ME, Rourke DA, et al. Analgesic administration, pain intensity, and patient satisfaction in cardiac surgical patients. Am J Crit Care 1995;4:435–42.
16. Moore R, Follette DM, Berkoff HA. Poststernotomy fractures and pain management in open cardiac surgery. Chest 1994;106:1339–42.
17. Greenwald LV, Baisden CE, Symbas PN. Rib fractures in coronary bypass patients: radionuclide detection. Radiology 1983;148:553–4.
18. Ho SC, Royse CF, Royse AG, et al. Persistent pain after cardiac surgery: an audit of high thoracic epidural and primary opioid analgesia therapies. Anesth Analg 2002;95:820–3.
19. Kalso E, Mennander S, Tasmuth T, Nilsson E. Chronic post-sternotomy pain. Acta Anaesthesiol Scand 2001;45:935–9.
20. Chaney MA, Morales M, Bakhos M. Severe incisional pain and long thoracic nerve injury after port-access minimally invasive mitral valve surgery. Anesth Analg 2000;91:288–90.
21. Davis Z, Jacobs HK, Zhang M, Castellanos Y. Endoscopic vein harvest for coronary artery bypass grafting: technique and outcomes. J Thorac Cardiovasc Surg 1998;116:228–35.
22. Smith RC, Leung JM, Mangano DT, SPI Research Group. Postoperative myocardial ischemia in patients undergoing coronary artery bypass graft surgery. Anesthesiology 1991;74:464–73.
23. Leung JM, O’Kelly B, Browner WS, et al. Prognostic importance of postbypass regional wall-motion abnormalities in patients undergoing coronary artery bypass graft surgery. Anesthesiology 1989;71:16–25.
24. Philbin DM, Rosow CE, Schneider RC, et al. Fentanyl and sufentanil anesthesia revisited: how much is enough? Anesthesiology 1990;73:5–11.
25. Reves JG, Karp RB, Buttner EE, et al. Neuronal and adrenomedullary catecholamine release in response to cardiopulmonary bypass in man. Circulation 1982;66:49–55.
26. Roberts AJ, Niarchos AP, Subramanian VA, et al. Systemic hypertension associated with coronary artery bypass surgery: predisposing factors, hemodynamic characteristics, humoral profile, and treatment. J Thorac Cardiovasc Surg 1977;74:846–59.
27. Liu S, Carpenter RL, Neal MJ. Epidural anesthesia and analgesia: their role in postoperative outcome. Anesthesiology 1995;82:1474–506.
28. Wu CL, Naqibuddin M, Rowlingson AJ, et al. The effect of pain on health-related quality of life in the immediate postoperative period. Anesth Analg 2003;97:1078–85.
29. Rogers MC. Do the right thing: pain relief in infants and children. N Engl J Med 1992;326:55–6.
30. Chaney MA. Intrathecal and epidural anesthesia and analgesia for cardiac surgery. Anesth Analg 1997;84:1211–21.
31. Feigl E. Coronary physiology. Physiol Rev 1983;63:1–205.
32. Lee DDP, Kimura S, DeQuattro V. Noradrenergic activity and silent ischaemia in hypertensive patients with stable angina: effect of metoprolol. Lancet 1989;1:403–6.
33. Vanhoutte PM, Shimokawa H. Endothelium-derived relaxing factor and coronary vasospasm. Circulation 1989;80:1–9.
34. Blomberg S, Emanuelsson H, Kvist H, et al. Effects of thoracic epidural anesthesia on coronary arteries and arterioles in patients with coronary artery disease. Anesthesiology 1990;73:840–7.
35. Blomberg S, Curelaru I, Emanuelsson H, et al. Thoracic epidural anaesthesia in patients with unstable angina pectoris. Eur Heart J 1989;10:437–44.
36. Heusch G, Deussen A, Thamer V. Cardiac sympathetic nerve activity and progressive vasoconstriction distal to coronary stenosis: feed-back aggravation of myocardial ischemia. J Auton Nerv Syst 1985;13:311–26.
37. Heusch G, Deussen A. The effects of cardiac sympathetic nerve stimulation on perfusion of stenotic coronary arteries in the dog. Circ Res 1983;53:8–15.
38. Uchida Y, Murao S. Excitation of afferent cardiac sympathetic nerve fibers during coronary occlusion. Am J Physiol 1974;226:1094–9.
39. Mangano DT. Perioperative cardiac morbidity. Anesthesiology 1990;72:153–84.
40. Birkett DA, Apthorp GH, Chamberlain DA, et al. Bilateral upper thoracic sympathectomy in angina pectoris: results in 52 cases. BMJ 1965;2:187–90.
41. Kock M, Blomberg S, Emanuelsson H, et al. Thoracic epidural anesthesia improves global and regional left ventricular function during stress-induced myocardial ischemia in patients with coronary artery disease. Anesth Analg 1990;71:625–30.
42. Blomberg SG. Long-term home self-treatment with high thoracic epidural anesthesia in patients with severe coronary artery disease. Anesth Analg 1994;79:413–21.
43. Davis RF, DeBoer LWV, Maroko PR. Thoracic epidural anesthesia reduces myocardial infarct size after coronary artery occlusion in dogs. Anesth Analg 1986;65:711–7.
44. Klassen GA, Bramwell RS, Bromage PR, Zborowska-Sluis DT. Effect of acute sympathectomy by epidural anesthesia on the canine coronary circulation. Anesthesiology 1980;52:8–15.
45. Mathews ET, Abrams LD. Intrathecal morphine in open heart surgery. Lancet 1980;2:543.
46. Bowler I, Djaiani G, Abel R, et al. A combination of intrathecal morphine and remifentanil anesthesia for fast-track cardiac anesthesia and surgery. J Cardiothorac Vasc Anesth 2002;16:709–14.
47. Alhashemi JA, Sharpe MD, Harris CL, et al. Effect of subarachnoid morphine administration on extubation time after coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2000;14:639–44.
48. Latham P, Zarate E, White PF, et al. Fast-track cardiac anesthesia: a comparison of remifentanil plus intrathecal morphine with sufentanil in a desflurane-based anesthetic. J Cardiothorac Vasc Anesth 2000;14:645–51.
49. Zarate E, Latham P, White PF, et al. Fast-track cardiac anesthesia: use of remifentanil combined with intrathecal morphine as an alternative to sufentanil during desflurane anesthesia. Anesth Analg 2000;91:283–7.
50. Peterson KL, DeCampli WM, Pike NA, et al. A report of two hundred twenty cases of regional anesthesia in pediatric cardiac surgery. Anesth Analg 2000;90:1014–9.
51. Hammer GB, Ngo K, Macario A. A retrospective examination of regional plus general anesthesia in children undergoing open heart surgery. Anesth Analg 2000;90:1020–4.
52. Chaney MA, Nikolov MP, Blakeman BP, Bakhos M. Intrathecal morphine for coronary artery bypass graft procedure and early extubation revisited. J Cardiothorac Vasc Anesth 1999;13:574–8.
53. Shroff A, Rooke GA, Bishop MJ. Effects of intrathecal opioid on extubation time, analgesia, and intensive care unit stay following coronary artery bypass grafting. J Clin Anesth 1997;9:415–9.
54. Chaney MA, Furry PA, Fluder EM, Slogoff S. Intrathecal morphine for coronary artery bypass grafting and early extubation. Anesth Analg 1997;84:241–8.
55. Chaney MA, Smith KR, Barclay JC, Slogoff S. Large-dose intrathecal morphine for coronary artery bypass grafting. Anesth Analg 1996;83:215–22.
56. Kowalewski R, MacAdams C, Froelich J, et al. Anesthesia supplemented with subarachnoid bupivacaine and morphine for coronary artery bypass surgery in a child with Kawasaki disease. J Cardiothorac Vasc Anesth 1996;10:243–6.
57. Taylor A, Healy M, McCarroll M, Moriarty DC. Intrathecal morphine: one year’s experience in cardiac surgical patients. J Cardiothorac Vasc Anesth 1996;10:225–8.
58. Kowalewski RJ, MacAdams CL, Eagle CJ, et al. Anaesthesia for coronary artery bypass surgery supplemented with subarachnoid bupivacaine and morphine: a report of 18 cases. Can J Anaesth 1994;41:1189–95.
59. Swenson JD, Hullander RM, Wingler K, Leivers D. Early extubation after cardiac surgery using combined intrathecal sufentanil and morphine. J Cardiothorac Vasc Anesth 1994;8:509–14.
60. Fitzpatrick GJ, Moriarty DC. Intrathecal morphine in the management of pain following cardiac surgery. a comparison with morphine i.v. Br J Anaesth 1988;60:639–44.
61. Vanstrum GS, Bjornson KM, Ilko R. Postoperative effects of intrathecal morphine in coronary artery bypass surgery. Anesth Analg 1988;67:261–7.
62. Casey WF, Wynands JE, Ralley FE, et al. The role of intrathecal morphine in the anesthetic management of patients undergoing coronary artery bypass surgery. J Cardiothorac Vasc Anesth 1987;1:510–6.
63. Cheun JK. Intraspinal narcotic anesthesia in open heart surgery. J Korean Med Sci 1987;2:225–9.
64. Aun C, Thomas D, St. John-Jones L, et al. Intrathecal morphine in cardiac surgery. Eur J Anaesthesiol 1985;2:419–26.
65. Jones SEF, Beasley JM, Macfarlane DWR, et al. Intrathecal morphine for postoperative pain relief in children. Br J Anaesth 1984;56:137–40.
66. Bettex DA, Schmidlin D, Chassot PG, Schmid ER. Intrathecal sufentanil-morphine shortens the duration of intubation and improves analgesia in fast-track cardiac surgery. Can J Anaesth 2002;49:711–7.
67. Goldstein S, Dean D, Kim SJ, et al. A survey of spinal and epidural techniques in adult cardiac surgery. J Cardiothorac Vasc Anesth 2001;15:158–68.
68. Boulanger A, Perreault S, Choiniere M, et al. Intrathecal morphine after cardiac surgery. Ann Pharm Fr 2002;36:1337–43.
69. Metz S, Schwann NM, Hassanein W, et al. Intrathecal morphine for off-pump coronary artery bypass grafting. J Cardiothorac Vasc Anesth 2004;18:451–3.
70. Lena P, Balarac N, Arnulf JJ, et al. Intrathecal morphine and clonidine for coronary artery bypass grafting. Br J Anaesth 2003;90:300–3.
71. Vincenty C, Malone B, Mathru M, et al. Comparison of intrathecal and intravenous morphine in post coronary bypass surgery. Crit Care Med 1985;13:308.
72. Hall R, Adderley N, MacLaren C, et al. Does intrathecal morphine alter the stress response following coronary artery bypass grafting surgery? Can J Anaesth 2000;47:463–6.
73. Lee TWR, Grocott HP, Schwinn D, et al. High spinal anesthesia for cardiac surgery: effects on β-adrenergic receptor function, stress response, and hemodynamics. Anesthesiology 2003;98:499–510.
74. Clowes GHA, Neville WE, Hopkins A, et al. Factors contributing to success or failure in the use of a pump oxygenator for complete by-pass of the heart and lung, experimental and clinical. Surgery 1954;36:557–79.
75. Hoar PF, Hickey RF, Ullyot DJ. Systemic hypertension following myocardial revascularization: a method of treatment using epidural anesthesia. J Thorac Cardiovasc Surg 1976;71:859–64.
76. El-Baz N, Goldin M. Continuous epidural infusion of morphine for pain relief after cardiac operations. J Thorac Cardiovasc Surg 1987;93:878–83.
77. Jideus L, Joachimsson PO, Stridsberg M, et al. Thoracic epidural anesthesia does not influence the occurrence of postoperative sustained atrial fibrillation. Ann Thorac Surg 2001;72:65–71.
78. Scott NB, Turfrey DJ, Ray DAA, et al. A prospective randomized study of the potential benefits of thoracic epidural anesthesia and analgesia in patients undergoing coronary artery bypass grafting. Anesth Analg 2001;93:528–35.
79. Warters D, Knight W, Koch SM, Luehr S. Thoracic epidurals in coronary artery bypass surgery. Anesth Analg 2000;90:767.
80. Loick HM, Schmidt C, Van Aken H, et al. High thoracic epidural anesthesia, but not clonidine, attenuates the perioperative stress response via sympatholysis and reduces the release of troponin T in patients undergoing coronary artery bypass grafting. Anesth Analg 1999;88:701–9.
81. Tenling A, Joachimsson PO, Tyden H, et al. Thoracic epidural anesthesia as an adjunct to general anesthesia for cardiac surgery: effects on ventilation-perfusion relationships. J Cardiothorac Vasc Anesth 1999;13:258–64.
82. Sanchez R, Nygard E. Epidural anesthesia in cardiac surgery: is there an increased risk? J Cardiothorac Vasc Anesth 1998;12:170–3.
83. Shayevitz JR, Merkel S, O’Kelly SW, et al. Lumbar epidural morphine infusions for children undergoing cardiac surgery. J Cardiothorac Vasc Anesth 1996;10:217–24.
84. Moore CM, Cross MH, Desborough JP, et al. Hormonal effects of thoracic extradural analgesia for cardiac surgery. Br J Anaesth 1995;75:387–93.
85. Stenseth R, Berg EM, Bjella L, et al. Effects of thoracic epidural analgesia on coronary hemodynamics and myocardial metabolism in coronary artery bypass surgery. J Cardiothorac Vasc Anesth 1995;9:503–9.
86. Kirno K, Friberg P, Grzegorczyk A, et al. Thoracic epidural anesthesia during coronary artery bypass surgery: effects on cardiac sympathetic activity, myocardial blood flow and metabolism, and central hemodynamics. Anesth Analg 1994;79:1075–81.
87. Stenseth R, Bjella L, Berg EM, et al. Thoracic epidural analgesia in aortocoronary bypass surgery. I: haemodynamic effects. Acta Anaesthesiol Scand 1994;38:826–33.
88. Stenseth R, Bjella L, Berg EM, et al. Thoracic epidural analgesia in aortocoronary bypass surgery. II: effects on the endocrine metabolic response. Acta Anaesthesiol Scand 1994;38:834–9.
89. Liem TH, Booij LHDJ, Hasenbos MAWM, Gielen MJM. Coronary artery bypass grafting using two different anesthetic techniques. I: hemodynamic results. J Cardiothorac Vasc Anesth 1992;6:148–55.
90. Liem TH, Hasenbos MAWM, Booij LHDJ, Gielen, MJM. Coronary artery bypass grafting using two different anesthetic techniques. I: postoperative outcome. J Cardiothorac Vasc Anesth 1992;6:156–61.
91. Liem TH, Booij LHDJ, Gielen MJM, et al. Coronary artery bypass grafting using two different anesthetic techniques. III: adrenergic responses. J Cardiothorac Vasc Anesth 1992;6:162–7.
92. Rosen KR, Rosen DA. Caudal epidural morphine for control of pain following open heart surgery in children. Anesthesiology 1989;70:418–21.
93. Joachimsson PO, Nystrom SO, Tyden H. Early extubation after coronary artery surgery in efficiently rewarmed patients: a postoperative comparison of opioid anesthesia versus inhalational anesthesia and thoracic epidural analgesia. J Cardiothorac Vasc Anesth 1989;3:444–54.
94. Robinson RJS, Brister S, Jones E, Quigly M. Epidural meperidine analgesia after cardiac surgery. Can Anaesth Soc J 1986;33:550–5.
95. Pastor MC, Sanchez MJ, Casas MA, et al. Thoracic epidural analgesia in coronary artery bypass graft surgery: seven years’ experience. J Cardiothorac Vasc Anesth 2003;17:154–9.
96. Vlachtsis H, Vohra A. High thoracic epidural with general anesthesia for combined off-pump coronary artery and aortic aneurysm surgery. J Cardiothorac Vasc Anesth 2003;17:226–9.
97. Sisillo E, Salvi L, Juliano G, et al. Thoracic epidural anesthesia as a bridge to redo coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2003;17:629–31.
98. Varadarajan B, Whitaker DK, Vohra A, Stafford SM. Thoracic epidural anesthesia in patients with ankylosing spondylitis undergoing coronary artery surgery. J Cardiothorac Vasc Anesth 2002;16:240–5.
99. de Vries AJ, Mariani MA, van der Maaten JMAA, et al. To ventilate or not after minimally invasive direct coronary artery bypass surgery: the role of epidural anesthesia. J Cardiothorac Vasc Anesth 2002;16:21–6.
100. Canto M, Casas A, Sanchez MJ, et al. Thoracic epidurals in heart valve surgery: neurologic risk evaluation. J Cardiothorac Vasc Anesth 2002;16:723–6.
101. Fillinger MP, Yeager MP, Dodds TM, et al. Epidural anesthesia and analgesia: effects on recovery from cardiac surgery. J Cardiothorac Vasc Anesth 2002;16:15–20.
102. Dhole S, Mehta Y, Saxena H, et al. Comparison of continuous thoracic epidural and paravertebral blocks for postoperative analgesia after minimally invasive direct coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2001;15:288–92.
103. Djaiani GN, Ali M, Heinrich L, et al. Ultra-fast-track anesthetic technique facilitates operating room extubation in patients undergoing off-pump coronary revascularization surgery. J Cardiothorac Vasc Anesth 2001;15:152–7.
104. Visser WA, Liem TH, Brouwer RMHJ. High thoracic epidural anesthesia for coronary artery bypass graft surgery in a patient with severe obstructive lung disease. J Cardiothorac Vasc Anesth 2001;15:758–60.
105. Liem TH, Williams JP, Hensens AG, Singh SK. Minimally invasive direct coronary artery bypass procedure using a high thoracic epidural plus general anesthetic technique. J Cardiothorac Vasc Anesth 1998;12:668–72.
106. Fawcett WJ, Edwards RE, Quinn AC, et al. Thoracic epidural analgesia started after cardiopulmonary bypass: adrenergic, cardiovascular and respiratory sequelae. Anaesthesia 1997;52:294–9.
107. Turfrey DJ, Ray DAA, Sutcliffe NP, et al. Thoracic epidural anaesthesia for coronary artery bypass graft surgery: effects on postoperative complications. Anaesthesia 1997;52:1090–5.
108. Stenseth R, Bjella L, Berg EM, et al. Effects of thoracic epidural analgesia on pulmonary function after coronary artery bypass surgery. Eur J Cardiothorac Surg 1996;10:859–65.
109. O’Connor CJ, Tuman KJ. Epidural anesthesia and analgesia for coronary artery bypass graft surgery: still forbidden territory? Anesth Analg 2001;93:523–5.
110. Amar D. Beta-adrenergic blocker withdrawal confounds the benefits of epidural analgesia with sympathectomy on supraventricular arrhythmias after cardiac surgery. Anesth Analg 2002;95:1119.
111. Riedel BJ, Shaw AD. Thoracic epidural anesthesia and analgesia in patients undergoing coronary artery bypass surgery. Anesth Analg 2002;94:1365.
112. Alston RP. Thoracic epidurals and coronary artery bypass grafting surgery. Anesth Analg 2002;94:1365.
113. Royse C, Royse A, Soeding P, et al. Prospective randomized trial of high thoracic epidural analgesia for coronary artery bypass surgery. Ann Thorac Surg 2003;75:93–100.
114. Priestley MC, Cope L, Halliwell R, et al. Thoracic epidural anesthesia for cardiac surgery: the effects on tracheal intubation time and length of hospital stay. Anesth Analg 2002;94:275–82.
115. Karagoz HY, Sonmez B, Bakkaloglu B, et al. Coronary artery bypass grafting in the conscious patient without endotracheal general anesthesia. Ann Thorac Surg 2000;70:91–6.
116. Aybek T, Dogan S, Neidhart G, et al. Coronary artery bypass grafting through complete sternotomy in conscious patients. Heart Surg Forum 2002;5:17–21.
117. Souto GLL, Junior CSC, de Souza JBS, et al. Coronary artery bypass in the ambulatory patient. J Thorac Cardiovasc Surg 2002;123:1008–9.
118. Aybek T, Kessler P, Dogan S, et al. Awake coronary artery bypass grafting: utopia or reality? Ann Thorac Surg 2003;75:1165–70.
119. Aybek T, Kessler P, Khan MF, et al. Operative techniques in awake coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;125:1394–400.
120. Karagoz HY, Kurtoglu M, Bakkaloglu B, et al. Coronary artery bypass grafting in the awake patient: three years’ experience in 137 patients. J Thorac Cardiovasc Surg 2003;125:1401–4.
121. Chakravarthy M, Jawali V, Patil TA, et al. High thoracic epidural anesthesia as the sole anesthetic for redo off-pump coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2003;17:84–6.
122. Chakravarthy MR, Jawali V, Patil TA, et al. High thoracic epidural anaesthesia as the sole anaesthetic technique for minimally invasive direct coronary artery bypass in a high-risk patient. Ann Cardiac Anaesth 2003;6:62–4.
123. Kessler P, Neidhart G, Bremerich DH, et al. High thoracic epidural anesthesia for coronary artery bypass grafting using two different surgical approaches in conscious patients. Anesth Analg 2002;95:791–7.
124. Vanek T, Straka Z, Brucek P, Widimsky P. Thoracic epidural anesthesia for off-pump coronary artery bypass without intubation. Eur J Cardiothorac Surg 2001;20:858–60.
125. Anderson MB, Kwong KF, Furst AJ, Salerno TA. Thoracic epidural anesthesia for coronary bypass via left anterior thoracotomy in the conscious patient. Eur J Cardiothorac Surg 2001;20:415–7.
126. Paiste J, Bjerke RJ, Williams JP, et al. Minimally invasive direct coronary artery bypass surgery under high thoracic epidural. Anesth Analg 2001;93:1486–8.
127. Zenati MA, Paiste J, Williams JP, et al. Minimally invasive coronary bypass without general endotracheal anesthesia. Ann Thorac Surg 2001;72:1380–2.
128. Chakravarthy M, Jawali V, Patil TA, et al. High thoracic epidural anesthesia as the sole anesthetic for performing multiple grafts in off-pump coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2003;17:160–4.
129. Schachner T, Bonatti J, Balogh D, et al. Aortic valve replacement in the conscious patient under regional anesthesia without endotracheal intubation. J Thorac Cardiovasc Surg 2003;125:1526–7.
130. Straka Z, Brucek P, Vanek T, et al. Routine immediate extubation for off-pump coronary artery bypass grafting without thoracic epidural analgesia. Ann Thorac Surg 2002;74:1544–7.
131. Liu SS, Block BM, Wu CL. Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: a meta-analysis. Anesthesiology 2004;101:153–61.
132. Ochroch EA, Gottschalk A, Augostides J, et al. Long-term pain and activity during recovery from major thoracotomy using thoracic epidural analgesia. Anesthesiology 2002;97:1234–44.
133. Richard C, Girard F, Ferraro P, et al. Acute postoperative pain in lung transplant recipients. Ann Thorac Surg 2004;77:1951–5.
134. Ballantyne JC, Carr DB, deFerranti S, et al. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials. Anesth Analg 1998;86:598–612.
135. Licker M, de Perrot M, Hohn L, et al. Perioperative mortality and major cardio-pulmonary complications after lung surgery for non-small cell carcinoma. Eur J Cardiothorac Surg 1999;15:314–9.
136. Sivarajan M, Amory DW, Lindbloom LE, Schuettmann RS. Systemic and regional blood-flow changes during spinal anesthesia in the rhesus monkey. Anesthesiology 1975;43:78–88.
137. Hackel DB, Sancetta SM, Kleinerman J. Effect of hypotension due to spinal anesthesia on coronary blood flow and myocardial metabolism in man. Circulation 1956;13:92–7.
138. Reiz S, Nath S, Rais O. Effects of thoracic epidural block and prenalterol on coronary vascular resistance and myocardial metabolism in patients with coronary artery disease. Acta Anaesthesiol Scand 1980;24:11–6.
139. DiNardo JA, Bert A, Schwartz MJ, et al. Effects of vasoactive drugs on flows through left internal mammary artery and saphenous vein grafts in man. J Thorac Cardiovasc Surg 1991;102:730–5.
140. Heusch G. α-adrenergic mechanisms in myocardial ischemia. Circulation 1990;81:1–13.
141. Reiz S, Nath S. Cardiotoxicity of local anaesthetic agents. Br J Anaesth 1986;58:736–46.
142. Wattwil M, Sundberg A, Arvill A, Lennquist C. Circulatory changes during high thoracic epidural anaesthesia: influence of sympathetic block and of systemic effect of the local anaesthetic. Acta Anaesthesiol Scand 1985;29:849–55.
143. Blomberg S, Ricksten SE. Effects of thoracic epidural anaesthesia on central haemodynamics compared to cardiac beta adrenoceptor blockade in conscious rats with acute myocardial infarction. Acta Anaesthesiol Scand 1990;34:1–7.
144. Hotvedt R, Refsum H, Platou ES. Cardiac electrophysiological and hemodynamic effects of β-adrenoceptor blockade and thoracic epidural analgesia in the dog. Anesth Analg 1984;63:817–24.
145. Chakravarthy M, Nadiminto S, Krishnamuthy J, et al. Temporary neurologic deficits in patients undergoing cardiac surgery with thoracic epidural supplementation. J Cardiothorac Vasc Anesth 2004;18:512–20.
146. Easley RB, Rosen RE, Lindeman KS. Coronary artery spasm during initiation of epidural anesthesia. Anesthesiology 2003;99:1015–7.
147. Oden RV, Karagianes TG. Postoperative myocardial ischemia possibly masked by epidural fentanyl analgesia. Anesthesiology 1991;74:941–3.
148. Chaney MA. Side effects of intrathecal and epidural opioids. Can J Anaesth 1995;42:891–903.
149. Wang JK, Nauss LA, Thomas JE. Pain relief by intrathecally applied morphine in man. Anesthesiology 1979;50:149–51.
150. Behar M, Magora F, Olshwang D, Davidson JT. Epidural morphine in treatment of pain. Lancet 1979;1:527–9.
151. Glynn CJ, Mather LE, Cousins MJ, et al. Spinal narcotics and respiratory depression. Lancet 1979;2:356–7.
152. Liolios A, Andersen FH. Selective spinal analgesia. Lancet 1979;2:357.
153. Scott DB, McClure J. Selective epidural analgesia. Lancet 1979;1:1410–1.
154. Shook JE, Watkins WD, Camporesi EM. Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression. Am Rev Respir Dis 1990;142:895–909.
155. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth Analg 1994;79:1165–77.
156. Markham JW, Lynge HN, Stahlman EB. The syndrome of spontaneous spinal epidural hematoma report of three cases. J Neurosurg 1967;26:334–42.
157. Waldman SD, Feldstein GS, Waldman HJ, et al. Caudal administration of morphine sulfate in anticoagulated and thrombocytopenic patients. Anesth Analg 1987;66:267–8.
158. Odoom JA, Sih IL. Epidural analgesia and anticoagulant therapy: experience with one thousand cases of continuous epidurals. Anaesthesia 1983;38:254–9.
159. Owens EL, Kasten GW, Hessel EA. Spinal subarachnoid hematoma after lumbar puncture and heparinization: a case report, review of the literature, and discussion of anesthetic implications. Anesth Analg 1986;65:1201–7.
160. Brem SS, Hafler DA, Van Uitert RL, et al. Spinal subarachnoid hematoma: a hazard of lumbar puncture resulting in reversible paraplegia. N Engl J Med 1981;303:1020–1.
161. Ruff RL, Dougherty JH. Complications of lumbar puncture followed by anticoagulation. Stroke 1981;12:879–81.
162. Varkey GP, Brindle GF. Peridural anaesthesia and anti-coagulant therapy. Can Anaesth Soc J 1974;21:106–9.
163. Baron HC, LaRaja RD, Rossi G, Atkinson D. Continuous epidural analgesia in the heparinized vascular surgical patient: a retrospective review of 912 patients. J Vasc Surg 1987;6:144–6.
164. Rao TLK, El-Etr AA. Anticoagulation following placement of epidural and subarachnoid catheters: an evaluation of neurologic sequelae. Anesthesiology 1981;55:618–20.
165. Ho AMH, Chung DC, Joynt GM. Neuraxial blockade and hematoma in cardiac surgery: estimating the risk of a rare adverse event that has not (yet) occurred. Chest 2000;117:551–5.
166. Rosen DA, Hawkinberry DW, Rosen KR, et al. An epidural hematoma in an adolescent patient after cardiac surgery. Anesth Analg 2004;98:966–9.
167. Chaney M, Labovsky J. Case report of thoracic epidural anesthesia and cardiac surgery balancing postoperative risks associated with hematoma formation and thromboembolic phenomenon. J Cardiothorac Vasc Anesth. In press.
168. Mora Mangano CT. Risky business. J Thorac Cardiovasc Surg 2003;125:1204–7.
169. Castellano JM, Durbin CG. Epidural analgesia and cardiac surgery: worth the risk? Chest 2003;117:305–7.
170. Schwann NM, Chaney MA. No pain, much gain? J Thorac Cardiovasc Surg 2003;126:1261–4.
171. Gravlee GP. Epidural analgesia and coronary artery bypass grafting: the controversy continues. J Cardiothorac Vasc Anesth 2003;17:151–3.
172. de Leon-Casasola OA. When it comes to outcome, we need to define what a perioperative epidural technique is. Anesth Analg 2003;96:315–8.
173. Rosenquist RW, Birnbach DJ. Epidural insertion in anesthetized adults: will your patients thank you? Anesth Analg 2003;96:1545–6.
174. Myles PS, Hunt JO, Fletcher H, et al. Relation between quality of recovery in hospital and quality of life at 3 months after cardiac surgery. Anesthesiology 2001;95:862–7.
175. Fleron MH, Weiskopf RB, Bertrand M, et al. A comparison of intrathecal opioid and intravenous analgesia for the incidence of cardiovascular, respiratory, and renal complications after abdominal aortic surgery. Anesth Analg 2003;97:2–12.
176. Beattie WS, Badner NH, Choi P. Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis. Anesth Analg 2001;93:853–8.
177. Wu CL, Raja SN. Optimizing postoperative analgesia: the use of global outcome measures. Anesthesiology 2002;97:533–4.
178. Gottschalk A, Ochroch EA. Preemptive analgesia: what do we do now? Anesthesiology 2003;98:280–1.
179. Hogan QH. No preemptive analgesia: is that so bad? Anesthesiology 2002;96:526–7.
180. Moiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia. Anesthesiology 2002;96:725–41.
181. Katz J, Cohen L, Schmid R, et al. Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization. Anesthesiology 2003;98:1449–60.
182. Chaney M. Cardiac surgery and intrathecal/epidural techniques: at the crossroads? Can Anaesth Soc J. In press.
This article has been cited 4 time(s).
Cochrane Database of Systematic ReviewsEpidural analgesia for cardiac surgeryCochrane Database of Systematic Reviews
Journal of Cardiothoracic and Vascular AnesthesiaThoracic Epidural Anesthesia Improves Early Outcome in Patients Undergoing Cardiac Surgery for Mitral Regurgitation: A Propensity-Matched StudyJournal of Cardiothoracic and Vascular Anesthesia
Journal of Thoracic and Cardiovascular SurgeryIs there any benefit in using awake anesthesia with thoracic epidural in thoracoscopic talc pleurodesis?Journal of Thoracic and Cardiovascular Surgery
Vojnosanitetski PregledBlood transfusion in cardiac surgery - Does the choice of anesthesia or type of surgery matter?Vojnosanitetski Pregled
© 2006 International Anesthesia Research Society