Epidural Anesthesia and Analgesia


Based on Hadzic’s Textbook of RAPM 2nd Ed 2017
Artwork by Vali Lancea


Clinical indications for epidural anesthesia and analgesia have expanded significantly over the past several decades. Epidural analgesia is often used to supplement general anesthesia (GA) for surgical procedures in patients of all ages with moderate-to- severe comorbid disease; provide analgesia in the intraoperative, postoperative, peripartum, and end-of-life settings; and can be used as the primary anesthetic for surgeries from the mediastinum to the lower extremities. In addition, epidural techniques are used increasingly for diagnostic procedures, acute pain therapy, and management of chronic pain. Epidural blockade may also reduce the surgical stress response, the risk of cancer recurrence, the incidence of perioperative thromboembolic events, and, possibly, the morbidity and mortality associated with major surgery.

This chapter covers the essentials of epidural anesthesia and analgesia. After a brief history of the transformation from single-shot to continuous epidural catheter techniques, it review (1) indications for and contraindications to epidural blockade; (2) basic anatomic considerations for epidural placement; (3) physiologic effects of epidural blockade; (4) pharmacology of drugs used for epidural anesthesia and analgesia; (5) techniques for successful epidural placement; and (6) major and minor complications associated with epidural blockade. This chapter also addresses several areas of controversy concerning epidural techniques. These include controversies about epidural space anatomy, the traditional epinephrine test dose, methods used to identify the epidural space, and whether particular clinical out- comes may be improved with epidural techniques when com- pared to GA. More detailed information about local anesthetics (LAs), the mechanism of neuraxial blockade, the combined spinal-epidural (CSE) technique, obstetric anesthesia, and complications of central neuraxial blockade is provided else- where in this textbook.

Brief History

The neurologist J. Leonard Corning proposed injecting an anesthetic solution into the epidural space in the 1880s, but devoted his research primarily to subarachnoid blocks. Despite coining the term spinal anesthesia, he may unknowingly have been investigating the epidural space. The French physicians Jean Sicard and Fernand Cathelin are credited with the first intentional administration of epidural anesthesia. At the turn of the 20th century, they independently introduced single-shot caudal blocks with cocaine for neurologic and genitourinary procedures, respectively.1Nineteen years later, the Spanish surgeon Fidel Pagés Miravé described a single-shot thoracolumbar approach to “peridural” anesthesia, identifying the epidural space through subtle tactile distinctions in the ligaments.2Within a decade and seemingly without the knowledge of Pagés’s work, the Italian surgeon Achille Dogliotti popularized a reproducible loss-of-resistance (LOR) technique to identify the epidural space.3Contemporaneously, the Argentine surgeon Alberto Gutiérrez described the “sign of the drop” for identification of the epidural space.

A number of innovations by Eugene Aburel, Robert Hingson, Waldo Edwards, and James Southworth, among others, attempted to prolong the single-shot epidural technique. However, Cuban anesthesiologist Manual Martinez Curbelo is credited with adapting Edward Tuohy’s continuous subarachnoid technique for the epidural space in 1947. His efforts were facilitated by an extensive knowledge of anatomy, a first-hand experience observing Tuohy at the Mayo Clinic, and the avail- ability of 16-gauge Tuohy needles and small, gradated 3.5-French ureteral catheters, which curved as they exited the tip of the needle.4 Several modifications of the Tuohy needle, itself a modification of the Huber needle, have since emerged.

The epidural catheter has also evolved from its origins as a modified ureteral catheter. Several manufacturers currently use nylon blends to produce thin, kink-resistant catheters of appropriate tensile strength and stiffness. The wire-reinforced catheter represents the most recent technological advance in epidural catheter design. The addition of a circumferential stainless steel coil within a nylon or polyurethane catheter confers greater flexibility compared to standard nylon catheters and may decrease the incidence of venous cannulation, intrathecal placement, catheter migration, and paresthesias.


This section presents common and controversial indications for the use of lumbar and thoracic epidural blockade in lower extremity, genitourinary, vascular, gynecologic, colorectal, and cardiothoracic surgery. It also reviews less common and novel indications for epidural anesthesia and analgesia, including for the treatment of patients with sepsis and uncommon medical disorders (Table 1). The use of neuraxial blockade for obstetric patients, pediatric surgery, and chronic pain and in the ambulatory setting is covered in greater detail elsewhere in this textbook.

TABLE 1. Examples of applications for epidural blockade.


Surgical Procedure

Orthopedic surgery

Major hip and knee surgery, pelvic fractures

Obstetric surgery

Cesarean delivery, labor analgesia

Gynecologic surgery

Hysterectomy, pelvic floor procedures

General surgery

Breast, hepatic, gastric, colonic surgery

Pediatric surgery

Inguinal hernia repair, orthopedic surgery

Ambulatory surgery

Foot, knee, hip, anorectal surgery

Cardiothoracic surgery

Thoracotomy, esophagectomy, thymectomy, coronary artery bypass grafting (on and off pump)

Urologic surgery

Prostatectomy, cystectomy, lithotripsy, nephrectomy

Vascular surgery

Amputation of lower extremity, revascularization procedures

Medical conditions

Autonomic hyperreflexia, myasthenia gravis, pheochromocytoma, known or suspected malignant hyperthermia

Lumbar Epidural Blockade

Epidural anesthesia has been administered most commonly for procedures involving the lower limbs, pelvis, perineum, and lower abdomen but is increasingly being used as the sole anesthetic or as a complement to GA for a greater diversity of procedures. This section examines several common indications for lumbar epidural blockade, including lower extremity orthopedic surgery, infrainguinal vascular procedures, and genitourinary and vaginal gynecologic surgeries. When applicable, it reviews the benefits and drawbacks of the use of neuraxial techniques versus GA for specific procedures.

Lower Extremity Major Orthopedic Surgery

Both perioperative anticoagulant thromboprophylaxis and the increasing reliance on peripheral nerve blocks have influenced the current use of continuous lumbar epidural blockade for lower extremity surgery. Nonetheless, neuraxial blockade as a sole anesthetic or as a supplement to either GA or peripheral techniques is still widely used for major orthopedic surgeries of the lower extremities. The effective postoperative pain control provided by either peripheral or neuraxial blocks, or a combination of the two techniques, improves patient satisfaction, permits early ambulation, accelerates functional recuperation, and may shorten hospital stay, particularly after major knee surgery. Other potential benefits of the use of neuraxial blockade in lieu of GA include the reduced incidence of deep vein thrombosis (DVT) in patients undergoing total hip5 and knee6 replacement surgery, improved postoperative cognitive function, and decreased intraoperative blood loss and transfusion requirements.7 A recent meta-analysis also demonstrated a statistically significant reduction in operative time when neuraxial blockade was used in patients undergoing elective total hip replacement, although the authors did not distinguish between spinal and epidural techniques.8

Major orthopedic procedures that can be performed under epidural, CSE, or integrated epidural and GA include primary hip or knee arthroplasty, surgery for hip fracture, revision arthroplasty, bilateral total knee arthroplasty, acetabular bone grafting, and insertion of long-stem femoral prostheses (Table 2). Spinal anesthesia may be the preferred technique in some of these cases, particularly if anticipated postoperative pain is slight or negligible (eg, total hip arthroplasty) or if a supplemental peripheral nerve block is planned. Anesthesia to T10 with needle placement at L3 to L4 is adequate for most of these procedures.

The use of neuraxial anesthesia for major orthopedic surgery is not without risks and challenges. Elderly patients, trauma victims, and individuals with hemophilia who develop complications from recurrent bleeding into their joints may not be appropriate candidates for regional blockade. In general, epidural procedures are well tolerated in patients with age-related comorbidities, such as restrictive pulmonary disease, prolonged hepatic clearance of drugs, hypertension (HTN), coronary artery disease (CAD), and renal insufficiency. Elderly patients may benefit from the decreased postoperative confusion and delirium associated with regional anesthesia, provided intraop- erative hypotension is kept to a minimum.9 However, prevention of excessive sympathectomy-induced hemodynamic changes can be challenging, as these patients are both less capable of responding to hypotension and more prone to cardiac decompensation and pulmonary edema in response to rapid fluid administration. An epidural technique with a sensory level below T10, as appropriate for many orthopedic surgeries, and judicious administration of fluids and vasopressors may minimize these risks.

Elderly patients commonly present for surgery on anticoagulant or antiplatelet medications and may pose a risk for neurologic injury related to central neuraxial blockade. If an epidural technique is selected for these or other high-risk patients, appropriate timing of both blockade initiation and catheter removal relative to the timing of anticoagulant drug administration must be taken into account. For trauma patients, attaining proper positioning for administration of epidural anesthesia may present a challenge. Initiation of neuraxial blockade in the lateral position may improve chances of success.

Intraoperatively, tourniquet pain can be anticipated with either spinal or epidural blockade, but occurs more frequently with the latter. While the mechanism remains poorly understood, it commonly presents within an hour of tourniquet inflation, increases in intensity over time, and is accompanied by tachycardia and elevated blood pressure. The administration of intrathecal or epidural preservative-free morphine may delay the onset of tourniquet pain.10

TABLE 2. Orthopedic surgeries suitable for epidural, combined spinal-epidural, or integrated epidural–general anesthesia.


Sensory Level Required

Closed reduction and external fixation of pelvis

Neuraxial technique seldom adequate for surgery; epidural useful for postoperative analgesia

Hip arthroplasty, arthrodesis, synovectomy


Open reduction internal fixation of acetabular fracture


Open reduction internal fixation of femur, tibia, ankle, or foot


Closed reduction and external fixation of femur and tibia


Above- and below-knee amputation

T12 (T8 with tourniquet)

Knee arthrotomy

T12 (T8 with tourniquet)

Arthroscopy of knee


Repair/reconstruction of knee ligaments


Total knee replacement

T12 (T8 with tourniquet)

Distal tibia, ankle, and foot procedures


Ankle arthroscopy, arthrotomy, arthrodesis


Transmetatarsal amputation


Lower Limb Vascular Surgery

There are several potential benefits of the use of neuraxial anesthesia and analgesia for lower extremity vascular procedures. Patients undergoing vascular surgery commonly have multiple major systemic diseases, such as CAD, cerebrovascular disease (CVD), diabetes mellitus (DM), chronic renal insufficiency, chronic HTN, and chronic obstructive pulmonary disease (COPD). Patients who present for arterial embolectomy may also have conditions that predispose them to intracardiac thrombus formation, such as mitral stenosis or atrial fibrillation. Avoiding GA in this high-risk patient population possibly enhances graft patency, reducing the need for reexploration and reducing the risk of thromboembolic complications; these are some of the advantages of using regional anesthesia. However, management of these individuals is often complicated by the high probability that they are taking presurgical antiplatelet or anticoagulant medications and will require additional systemic anticoagulation intraoperatively and postoperatively. Thus, these patients are considered at an increased risk for epidural hematoma; a careful risk-benefit analysis is necessary prior to initiating epidural blockade. Consideration must also be given to the type of vascular procedure to be performed, the anticipated length of the procedure, the possible need for invasive monitoring, and the timely removal of the epidural catheter before transitioning to oral anticoagulation therapy. Maintaining normothermia, ensuring that motor strength can be promptly assessed postoperatively, and providing appropriate sedation during lengthy procedures are additional challenges.

Infrainguinal vascular procedures that are suitable for epidural blockade include arterial bypass surgeries, arterial embolectomy, and venous thrombectomy or vein excision(Table 3). Slow titration of LAs to attain a T8–T10 level, while maintaining hemodynamic stability, is optimal. The addition of epinephrine to LAs is controversial due to concerns that its vasoconstrictive effect may jeopardize an already-tenuous blood supply to the spinal cord. Studies to date have failed to demonstrate a difference in cardiovascular and pulmonary morbidity and mortality with the use of epidural anesthesia as com- pared with GA for these procedures,11 although epidural techniques may be superior for promoting graft survival.

TABLE 3. Examples of vascular procedures performed with epidural blockade.

Abdominal aortic aneurysm repair (neuraxial technique seldom adequate as sole anesthetic)

Aortofemoral bypass

Renal artery bypass

Mesenteric artery bypass

Infrainguinal arterial bypass with saphenous vein or synthetic graft



Endovascular procedures (intraluminal balloon dilation with stent placement; aneurysm repair)

Lower Genitourinary Procedures

Lumbar epidural blockade as either a primary anesthetic or as an adjunct to GA is an appropriate option for a variety of genitourinary procedures. Epidural anesthesia with a T9–T10 sensory level can be used for transurethral resection of the prostate (TURP), although spinal anesthesia may be preferred due to its improved sacral coverage, denser sensory blockade, and shorter duration. Both techniques are considered superior to GA for several reasons, including earlier detection of mental status changes associated with TURP syndrome; the ability of the patient to communicate breakthrough pain if an untoward complication such as perforation of the prostatic capsule or bladder occurs; the potential for decreased bleeding; and the decreased risks of perioperative thromboembolic events and fluid overload (Table 4).12 In addition, patients presenting for this and other prostate surgeries are generally elderly, with multiple comorbidities, and have a low risk for certain complications of neuraxial blockade, such as postdural puncture headache (PDPH).

TABLE 4. Benefits of central neuraxial blockade versus general anesthesia for transurethral resection of the prostate.

Early detection of mental status changes

Early detection of breakthrough pain (indicative of capsular/bladder perforation)

Reduced blood loss

Decreased incidence of deep vein thrombosis

Decreased incidence of circulatory overload

Improved postoperative pain control

Other transurethral procedures, such as cystoscopy and ureteral stone extraction, can be performed under GA, topical anesthesia, or neuraxial blockade, depending on the extent and complexity of the procedure, patient comorbidities, and patient, anesthesiologist, and surgeon preference. Of note, paraplegic and quadriplegic patients comprise a subset of patients who present for repeated cystoscopies and stone extraction procedures; neuraxial anesthesia is often preferred in these patientsbecause of the risk of autonomic hyperreflexia (AH) (see seprate section on this topic). Because these procedures are done on an outpatient basis, lengthy residual epidural blockade should be avoided. Although there is some interindividual variability, a sensory level as high as T8 is required for procedures involving the ureters, while a T9–T10 sensory level is appropriate for procedures involving the bladder(Table 5).

TABLE 5. Sensory level required for genitourinary procedures.


Sensory Level Required


Consider combined general-epidural anesthesia



Extracorporeal shock wave lithotripsy


Open prostatectomy


Ureteral stone extraction




Transurethral resection of prostate


Surgery involving testes


Surgery involving penis


Urethral procedures

Sacral block

Vaginal Gynecologic Surgeries

Several vaginal gynecologic surgeries can be performed with epidural blockade, although single-shot spinal or GA and, in some cases, paracervical block or topical anesthesia may be more appropriate(Table 6). A dilation and curettage (D&C) can be performed under paracervical block, GA, or neuraxial blockade. If neuraxial anesthesia is selected, a T10 sensory level is appropriate. While outpatient diagnostic hysteroscopy can be performed under LA,13 hysteroscopy with distention media typically requires general or neuraxial anesthesia. Epidural anesthesia may have the disadvantage of increased glycine absorption compared to GA.14 However, mental status changes related to absorption of the hypotonic irrigation solution are more easily detected in awake patients. For urinary incontinence procedures, epidural anesthesia offers the advantage of permitting the patient to participate in the intraoperative cough test, which theoretically decreases the risk of postoperative voiding dysfunction, although the incidence of this untoward outcome does not appear to be increased under GA.15A T10 sensory level provides sufficient anesthesia for bladder procedures, but the level should be extended to T4 if the peritoneum is opened. Vaginal hysterectomy can be performed under general or neuraxial (most commonly spinal) anesthesia. A T4–T6 sensory level is appropriate for uterine procedures.

TABLE 6. Vaginal gynecologic procedures suitable for epidural blockade.

Dilation and curettage

Hysteroscopy (with or without distention media)

Urinary incontinence procedures


Thoracic Epidural Anesthesia and Analgesia

The benefits of and indications for thoracic epidural anesthesia (TEA) are expanding (Table 7). TEA offers superior peri-operative analgesia compared with systemic opioids,16 decreases postoperative pulmonary complications,17 decreases the duration of postoperative ileus,18 and decreases mortality in patients with multiple rib fractures, among other things.19 This section explores the role of TEA as either a primary anesthetic or as an adjuvant to GA for cardiac, thoracic, abdominal, colorectal, genitourinary, and gynecologic surgery (Figure 1). It also reviews the expanding role of TEA for video-assisted thoracic surgery (VATS) and laparoscopic surgery.

TABLE 7. Benefits of thoracic epidural anesthesia and analgesia.

Improved perioperative analgesia compared with other modalities

Decreased postoperative pulmonary complications

Decreased duration of postoperative ileus

Decreased duration of mechanical ventilation

Decreased mortality in patients with rib fractures

Cardiac Surgery

High TEA (blockade of the upper five thoracic segments) as an adjuvant to GA in cardiac surgery with cardiopulmonary bypass (CPB) has gained interest over the past several decades. Purported benefits include improved distribution of coronary blood flow,20 reduced oxygen demand, improved regional left ventricular function, a reduction in the incidence of supraventricular arrhythmias,21 attenuation of the surgical stress response,22 improved intraoperative hemodynamic stability, faster recovery of awareness, improved postoperative analgesia, and a reduction of postoperative renal and pulmonary complications. Several of these potential benefits can be attributed to selective blockade of cardiac sympathetic innervation (the T1–T4 spinal segments). However, the insertion of an epidural catheter in patients requiring full heparinization for CPB carries the risk of epidural hematoma.

The evidence in support of high TEA for cardiac surgery is not conclusive. A study by Liu and colleagues comparing TEA with traditional opioid-based GA for coronary artery bypass grafting (CABG) with CPB found no difference in the rates of mortality or myocardial infarction, but demonstrated a statistically significant reduction in the risk of postoperative cardiac arrhythmias and pulmonary complications, improved pain scores, and earlier tracheal extubation in the TEA group.23 In contrast, a recent randomized control trial comparing the clinical effects of fast-track GA with TEA versus fast-track GA alone in over 600 patients undergoing elective cardiac surgery (both on pump and off pump) found no statistically significant difference in 30-day survival free from myocardial infarction, pulmonary complications, renal failure, or stroke.24The duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, and quality of life at 30-day follow- up were also similar for the two groups. Overall, the role of TEA as an adjuvant to GA for cardiac surgery with CPB remains controversial.

The role of high TEA in off-pump coronary artery bypass (OPCAB) surgery is also debated in the literature. TEA offers the advantages of avoiding intubation of the trachea in selected CABG cases, earlier extubation in patients receiving GA, and reduced postoperative pain and morbidity. But, concerns remain about compromised ventilation with a high sensory blockade, hypotension due to sympathicolysis, and epidural hematoma, despite the vastly reduced heparin dose compared with CPB cases. A recent prospective, randomized controlled trial of more than 200 patients undergoing OPCAB surgery found that the addition of high TEA to GA significantly reduced the incidence of postoperative arrhythmias, improved pain control, and improved the quality of recovery.25 Until more definitive outcome data are available, the role of neuraxial techniques in OPCAB surgery remains uncertain.


FIGURE 1:Level of placement in surgeries performed with thoracic epidural anesthesia and analgesia.

Thoracic and Upper Abdominal Surgical Procedures

Epidural anesthesia and analgesia are commonly used for upper abdominal and thoracic surgery, including gastrectomy, esophagectomy, lobectomy, and descending thoracic aorta procedures (Table 8). It is less commonly used for VATS, unless conversion to an open procedure is highly anticipated or if the patient is at high risk for complications from GA. Epidural blockade for many of these procedures commonly serves as an adjuvant to GA and as an essential component of postoperative pain management. Concurrent administration of high TEA with GA, however, carries risks of intraoperative bradycardia, hypotension, and changes in airway resistance. There is some debate regarding whether intraoperative activation of epidural blockade is required to appreciate the analgesic benefits of TEA or if postoperative activation produces equivalent benefits. A systematic review by Møiniche and colleagues found that the timing of several types of analgesia, including epidurals, intravenous opioids, and peripheral LAs, did not influence the quality of postoperative pain control.26

TABLE 8. Indications for thoracic epidural anesthesia and analgesia

Anatomic Region



Thoracotomy Pectus repair

Thoracic aneurysm repair Thymectomy

Video-assisted thoracic surgery

Upper abdomen

Esophagectomy Gastrectomy Pancreatectomy Cholecystecomy Hepatic resection

Lower abdomen

Abdominal aortic aneurysm repair Colectomy

Bowel resection

Abdominal perineal resection

Urogenital/ gynecologic

Cystectomy Nephrectomy Ureteral repair

Radical abdominal prostatectomy Ovarian tumor debulking

Pelvic exenteration

Total abdominal hysterectomy

Thoracic epidural anesthesia initiated at the mid- to upper thoracic region can also be used for breast procedures. Benefits may include superior postoperative analgesia, decreased incidence of postoperative nausea and vomiting (PONV), improved patient satisfaction, and avoiding tracheal intubation in patients with moderate-to-severe comorbidities.27The sensory level required depends on the procedure: A level extending from T1–T7 is adequate for breast augmentation; C5–T7 is required for modified radical mastectomy; and C5–L1 is required for mastectomy with transverse rectus abdominis myocutaneous (TRAM) flap reconstruction (Table 9).28 The epidural catheter can be introduced at T2–T4 to achieve segmental blockade of the thoracic dermatomes for most breast proce- dures; placement at T8–T10 is appropriate for TRAM flap reconstruction.

TABLE 9. Sensory level required for breast procedures.


Segmental Blockade

Modified radical mastectomy


Mastectomy with transverse rectus abdominus flap


Partial mastectomy; breast augmentation


Epidural blockade provides a useful adjuvant to GA for procedures within the thoracic cavity, such as lung and esophageal surgery. The benefits of TEA for these procedures include enhanced postoperative analgesia; reduced pulmonary morbidity (eg, atelectasis, pneumonia, and hypoxemia); swift resolution of postoperative ileus; and decreased postoperative catabolism, which may spare muscle mass. Segmental epidural blockade of T1–T10 provides sensory blockade of the thoracotomy incision and the chest tube insertion site.

Upper abdominal surgeries that can be performed with epidural anesthesia and analgesia include esophagectomy, gastrectomy, pancreatectomy, hepatic resection,29and cholecystectomy. Laparoscopic cholecystectomy with epidural blockade30 and distal gastrectomy with a combined general-epidural anesthetic have also been reported.31 Midthoracic epidural catheter placement with segmental blockade extending from T5 (T4 for laparoscopic surgery) to T8 is appropriate for most upper abdominal procedures and, due to lumbar and sacral nerve root sparing, has minimal risk of lower extremity motor deficits, urinary retention, hypotension, and other sequelae of lumbar epidural anesthesia.

Suprainguinal Vascular Procedures

An upper midthoracic epidural can be used as an adjuvant to GA for surgeries of the abdominal aorta and its major branches. Epidural blockade for aortofemoral bypass, renal artery bypass, and repair of abdominal aortic aneurysms may provide superior postoperative pain control, facilitate early extubation of the trachea, permit early ambulation, and decrease the risk of thromboembolic events in patients who are at particularly high risk for this untoward complication. However, intraoperative epidural blockade may complicate management of hemodynamic changes associated with aortic cross-clamping and unclamping, as well as compromise early assessment of motor function in the immediate postoperative period. A sensory level from T6 to T12 is necessary for an extensive abdominal incision; a level extending from T4–T12 is required to attain denervation of the viscera.

Extracorporeal Shock Wave Lithotripsy, Prostatectomy, Cystectomy, Nephrectomy

Extracorporeal shock wave lithotripsy (ESWL) with or without water immersion can be performed under general or neuraxial anesthesia. A T6–T12 sensory level is necessary when neuraxial techniques are selected. Epidural blockade is associated with less intraoperative hypotension than a single-shot spinal, although both techniques serve to avoid GA in potentially high-risk patients.

Open prostate surgery, radical cystectomy and urinary diversion, and simple, partial, and radical nephrectomy can be performed under neuraxial blockade, either alone or in combination with GA, depending on the procedure. Some potential advantages of neuraxial compared with GA for radical retropubic prostatectomy include decreased intraoperative blood loss and transfusions,32 a decreased incidence of postoperative thromboembolic events, improved analgesia and level of activity up to 9 weeks postoperatively,33 faster return of bowel function,34 and several other still-disputed advantages of neuraxial anesthesia, such as faster time to hospital discharge and reduced hospital costs. For the open procedure, patients may require generous sedation in the absence of a combined general-neuraxial technique. A T6 sensory level is required, with catheter placement in the midthoracic region. Radical cystectomy is performed on patients with invasive bladder cancer and may have improved outcomes with a combined general-epidural anesthetic compared to GA alone. Epidural blockade can provide controlled hypotension intraoperatively, contributing to decreased blood loss, and optimize postoperative pain relief.35 A midthoracic epidural with a T6 sensory level is appropriate. Although GA is often required for radical nephrectomy due to concerns for patient positioning, intraoperative hypotension, and the potential for significant intraoperative blood loss, epidural analgesia provides more effective postoperative pain relief than systemic opioids while avoiding the adverse effects of the latter.

Several other urologic-related surgeries can be performed with neuraxial blockade as the sole anesthetic or as an adjuvant to GA. The use of a combined GA-epidural technique in patients with functional adrenal tumors undergoing laparoscopic adrenalectomy is safe and effective and may have the added benefit of minimizing fluctuations in hormone levels. Of note, however, epidural blockade may not diminish the pressor effects of direct tumor stimulation. The use of epidural anesthesia for retroperitoneal laparoscopic biopsy for patients who are not candidates for percutaneous biopsy has also been reported.36

Lower Abdominal and Gynecologic Surgeries

Total abdominal hysterectomy is often performed under GA, a combined general-epidural anesthetic, or neuraxial anesthesia with or without sedation. Although still not routine, gynecologic laparoscopy is increasingly being performed under neuraxial anesthesia, commonly with decreased Trendelenburg tilt, reduced CO2 insufflation pressures (below 15 mm Hg), and supplemental opioids or nonsteroidal anti-inflammatory drugs (NSAIDs) to minimize referred shoulder pain. Epidural blockade for open procedures has the advantages of providing prolonged postoperative analgesia, decreasing the incidence of PONV and perioperative thromboembolic events, and potentially influencing perioperative immune function and, relatedly, the recurrence of cancer in patients undergoing hysterectomy for ovarian or related cancer. The proposed preemptive analgesia effect provided by neuraxial blockade during abdominal hysterectomy requires further investigation.37 A sensory level extending to T4 or T6 provides sufficient anesthesia for procedures involving the uterus. Either epidural catheter insertion in the lumbar region with high volumes of LAs to raise the sensory level or low- to midthoracic placement is appropriate. The visceral pain associated with bowel and peritoneal manipulation decreases as the level of the blockade is increased; a T3–T4 level may be optimal.38

Open and laparoscopic colectomy, sigmoidectomy, and appendectomy are among other lower abdominal surgeries that can be performed under neuraxial anesthesia, with or without GA. Of particular interest in patients undergoing bowel surgery, thoracic epidural blockade decreases the duration of postoperative ileus, possibly without affecting anastomotic healing and leakage.39 The superior postoperative analgesia associated with continuous epidural infusions, with or without opioids, most likely improves postoperative lung function in patients undergoing gastrointestinal (GI) surgery, although specific randomized controlled trials have not been conducted. In combination with early feeding and ambulation, TEA plays a role in early hospital discharge after certain GI surgeries.40 A similar outcome has been demonstrated after laparoscopic colonic resection, followed by epidural analgesia for 2 days and early oral nutrition and mobilization (ie, multimodal rehabilitation).41 Epidural catheter placement between T9 and T11 is usually appropriate for lower abdominal procedures; a sensory blockade extending to T7 or T9 is required for most colonic surgeries (sigmoid resection, ileotransversostomy, hemicolectomy).

Uncommon Medical Disorders and Clinical Scenarios


Epidural anesthesia and analgesia may also be indicated in the perioperative management of patients with specific medical conditions or coexisting disease, such as myasthenia gravis (MG), AH, malignant hyperthermia (MH), COPD, pheochromocytoma (see previous discussion), and sepsis. Several other subsets of patients may benefit from continuous epidural catheter techniques, including palliative care patients, parturients with comorbidities, and patients at risk for recurrent malignancy.

Myasthenia Gravis

Patients with MG pose particular challenges to anesthesiologists, including abnormal responses to depolarizing and nondepolarizing neuromuscular blocking agents; potential difficulty reversing residual neuromuscular blockade in patients taking cholinesterase inhibitors; prolonged postoperative mechanical ventilation requirements; risk of postsurgical respiratory failure; and postoperative pain management concerns.42 Epidural blockade eliminates the need for intraoperative muscle relaxants in myasthenic patients and provides superior postoperative pain relief compared with opioids, while minimizing the risk of opioid-induced respiratory depression and pulmonary dysfunction.43 Due to the possibility that ester LA metabolism may be prolonged in patients taking cholinesterase inhibitors, amide LAs may be preferred for the management of myasthenic patients. Reduced doses of LAs may also be appropriate. Concerns for compromising a myasthenic patient’s respiratory function with a high epidural appear to be unfounded.44

Autonomic Hyperreflexia

Epidural techniques are appropriate for the perioperative management of patients with AH. AH occurs in up to 85% of patients with spinal cord injuries at or above T4–T7 as a result of uninhibited sympathetic activity. In response to visceral or cutaneous stimulation below the level of the lesion and in the absence of descending central inhibition, patients may develop acute, extreme sympathetic hyperactivity. Generally, intense vasoconstriction occurs below the level of the spinal cord lesion, with vasodilation above. Patients may experience sweating, nausea, flushing, pallor, shivering, nasal obstruction, blurred vision, headache, difficulty breathing, seizures, and cardiac arrhythmias. Reflex bradycardia is seen in the majority of cases. Severe life-threatening HTN can result in intracranial hemorrhage, myocardial ischemia, pulmonary edema, and death. Epidural blockade as the sole anesthetic, as a supplement to GA, or for labor analgesia attenuates the physiologic perturbations associated with AH, although incomplete block of sacral segments or missed segments may contribute to a high failure rate.45 Spinal anesthesia, which blocks the afferent limb of this potentially lethal reflex, and deep GA more reliably prevent AH.46

Malignant Hyperthermia

The anesthetic management of MH presents a challenge to the anesthesiologist. MH is a clinical syndrome of markedly accelerated metabolism triggered primarily by volatile agents and the depolarizing agent succinylcholine. Susceptible patients may develop fever, tachycardia, hypercarbia, tachypnea, arrhythmias, hypoxemia, profuse sweating, HTN, myoglobinuria, mixed acidosis, and muscle rigidity in response to exposure to volatile agents or succinylcholine, although cases have been reported in which there is no evident triggering agent. Late complications may include consumptive coagulopathy, acute renal failure, muscle necrosis, pulmonary edema, and neurologic sequelae. Avoiding exposure to triggering agents is a cornerstone in the management of MH- susceptible patients. Whenever suitable, local, peripheral, or central neuraxial blocks are recommended, as these techniques are reported to be safer than the use of GA.47Both ester and amide LAs are considered safe in MH-susceptible patients, as is epinephrine, although controversy remains in the literature.

Chronic Obstructive Pulmonary Disease

Epidural blockade is a reasonable anesthetic option for patients with COPD undergoing major surgery due to concerns for prolonged mechanical ventilation. However, whether epidural techniques reduce pulmonary complications in patients with COPD is not known. In a recent propensity-controlled analysis of more than 500 patients with COPD undergoing abdominal surgery, epidural analgesia as an adjuvant to GA was associated with a statistically significant reduction in the risk of postoperative pneumonia.48 Patients with the most severe type of COPD benefited disproportionately. The study also found a nonsignificant beneficial effect of epidural analgesia on 30-day mortality, a trend that has been demonstrated in other studies.7

Pediatric Surgery

There is a considerable body of literature dedicated to the use of regional anesthesia for pediatric surgery in both the inpatient and the ambulatory settings. Advantages of neuraxial blockade for the pediatric population include optimal postoperative analgesia, which is particularly important in extensive scoliosis repair, repair of pectus excavatum, and major abdominal and thoracic procedures; decreased GA requirements; earlier awakening; and earlier discharge in the ambulatory setting. Certain subsets of pediatric patients, such as those with cystic fibrosis, a family history of MH, or a history of prematurity, also benefit from the use of neuraxial anesthesia in lieu of GA. However, parental refusal, concerns about performing regional blocks in anesthetized patients, and airway concerns in patients with limited oxygen reserves pose challenges to the routine use of neuraxial blockade in this patient population.

The single-shot caudal approach to the epidural space, with or without sedation, is commonly used in pediatric patients for a variety of surgeries, including circumcision, hypospadias repair, inguinal herniorrhaphy, and orchidopexy. Continuous caudal catheters may be advanced cephalad to higher vertebral levels and used as the sole anesthetic or as an adjuvant to GA. Lumbar anesthesia and TEA provide a more reliable sensory blockade at higher segmental levels in older children. See Chapter 42 on pediatric regional anesthesia for a more detailed discussion of caudal blocks.

Ambulatory Surgery

Spinal anesthesia or peripheral nerve blocks are preferred over epidural techniques for most clinical scenarios in the ambulatory setting due to concerns for the relatively slow onset of epidural blockade, urinary retention, prolonged immobility, PDPH, and delayed discharge. The use of short-acting LAs, when appropriate, may obviate these concerns. Epidural techniques have the advantages of permitting slow titration of LAs, the ability to tailor block height and duration to the surgical procedure, and a decreased risk of transient neurologic symptoms (TNS) when compared with spinal anesthesia. Total hip arthroplasty, knee arthroscopy, foot surgery, inguinal herniorrhaphy, pelvic laparoscopy, and anorectal procedures are among the many outpatient surgeries that can be performed with neuraxial blockade as the primary anesthetic.49 Regional blockade in the ambulatory setting is discussed in greater detail elsewhere in this volume.

Labor Analgesia and Anesthesia

Parturients comprise the single largest group to receive epidural analgesia. For adequate pain relief during the first stage of labor, coverage of the dermatomes from T10 to L1 is necessary; analgesia should extend caudally to S2–S4 (to include the pudendal nerve) during the second stage of labor. Epidural placement at the L3–L4 interspace is most common in laboring patients. However, surface anatomic landmarks may be difficult to appreciate in obstetric patients and may not reliably identify the intended interspace in this subset of patients due to both the anterior rotation of the pelvis and exaggerated lumbar lordosis. Several other factors may affect the ease of epidural placement and spread of epidurally administered LAs in parturients, including engorgement of epidural veins, elevated hormonal levels, and excessive weight gain. Refer to Chapter 41 for additional information on epidural techniques in laboring patients.


Several nonanesthetic applications for epidural procedures have emerged. Epidural catheter infusion techniques are being used increasingly for pain control at the end of life in both children and adults, including those with cancer-related pain.50 There is also an evolving interest in whether epidural anesthesia and analgesia may have a protective role in sepsis. Of particular interest is whether critically ill patients may benefit from the increased splanchnic organ perfusion and oxygenation, as well as immunomodulation, seen in healthy patients who have received epidural anesthesia. However, additional studies are needed to evaluate the risk and benefits of epidural techniques in sepsis.51 Another novel application for epidural LAs proposes that continuous infusions may improve placental blood flow in parturients with chronically compromised uterine perfusion and intrauterine growth restriction.52 There is a growing body of literature devoted to the potential beneficial effects of epidural analgesia in patients with cancer, although the data are preliminary and at times contradictory. Surgical stress and certain anesthetic agents suppress the host’s immune function, including its ability to eliminate circulating tumor cells, and can predispose patients with cancer to postoperative infection, tumor growth, and metastasis. Recent studies have demonstrated improved perioperative immune function with the use of TEA in patients undergoing elective laparoscopic radical hysterectomy for cervical cancer.53 Regional adjuncts to anesthesia have also been shown to have beneficial effects against recurrence of breast54 and prostate55cancer. These protective effects may reflect both the decreased opioid requirements and the reduced neurohumoral stress response associated with epidural blockade.56


Serious complications of epidural techniques are rare. However, epidural hematomas, epidural abscesses, permanent nerve injury, infection, and cardiovascular collapse, among other adverse events, have been attributed to neuraxial blockade. As a result, an understanding of the conditions that may predispose certain patient populations to these and other complications is essential. This section reviews the absolute, relative, and controversial contraindications to epidural placement (Table 10). Ultimately, a risk-benefit analysis with particular emphasis on patient comorbidities, airway anatomy, patient preferences, and type and duration of surgery is recommended prior to initiation of epidural blockade.

Absolute Contraindications


Although the contraindications to epidural blockade have been classified historically as absolute, relative, and controversial, opinions regarding absolute contraindications have evolved with advances in equipment, techniques, and practitioner experience. Currently, patient refusal may be considered the only absolute contraindication to epidural blockade. Although coagulopathy is considered a relative contraindication, initiating neuraxial blockade in the presence of severe coagulation abnormalities, such as frank disseminated intravascular coagulation (DIC), is contraindicated. Most other pathologic conditions comprise relative or controversial contraindications and require careful risk-benefit analysis prior to initiation of epidural blockade.

TABLE 10. Contraindications to epidural blockade.


Patient refusal

Severe coagulation abnormalities (eg, frank disseminated intravascular coagulation)

Relative and controversial


Elevated intracranial pressure Anticoagulants Thrombocytopenia

Other bleeding diatheses

Preexisting central nervous system disorders (eg, multiple sclerosis)

Fever/infection (eg, varicella zoster virus) Preload dependent states (eg, aortic stenosis)

Previous back surgery, preexisting neurologic injury, back pain

Placement in anesthetized adults Needle placement through tattoo


Relative and Controversial Contraindications Sepsis

There is growing interest in using epidural anesthesia and analgesia to modulate inflammatory responses and to prevent or treat myocardial ischemia, respiratory dysfunction, and splanchnic ischemia in septic patients. However, there is insufficient evidence to determine whether epidural blockade is harmful or protective in sepsis.57 Despite the potential benefits of regional techniques in this setting, many anesthesiologists may be reluctant to initiate epidural blockade in septic patients due to concerns for relative hypovolemia, refractory hypotension, coagulopathy, and the introduction of blood-borne pathogens into the epidural or subarachnoid space. If regional anesthesia is selected, a slow-onset dosing technique after or with concur- rent antibiotic, intravenous fluid, and vasopressor administration may be feasible.

Increased Intracranial Pressure

Accidental dural puncture (ADP) in the setting of elevated intra- cranial pressure (ICP) with radiologic evidence of obstructed cerebrospinal fluid (CSF) flow or mass effect with or without midline shift can place patients at risk of cerebral herniation and other neurological deterioration.58 Patients with increased ICP at baseline may also experience an additional increase in pressure on epidural drug injection.59 Consultation with a neurologic expert is strongly recommended, and localizing neurologic signs and symptoms should be ruled out by history and physical examination prior to initiation of neuraxial blockade in patients with new neurologic symptoms or known intracranial lesions60 (Table 11).

A decision tree may aid in assessing whether it is safe to proceed with neuraxial techniques in the presence of intracranial space-occupying lesions (Figure 2).

TABLE 11. Signs and symptoms of elevated intracranial pressure.

Headache Drowsiness

Nausea and vomiting New-onset seizures

Decreases level of consciousness Papilledema

Pupillary changes

Focal neurologic signs


Coagulopathy is a relative contraindication to epidural placement, although thorough consideration of the etiology and severity of the coagulopathy is warranted on a case-by-case basis. Anticoagulants increase the risk of epidural hematoma and should be withheld in a timely fashion before initiation of epidural blockade. Precautions should also be taken before epidural catheter removal, as catheter removal may be as traumatic as catheter placement.61


Epidural needle and catheter placement both carry a risk of epidural hematoma in patients on anticoagulants. Similar precautions should be observed during placement and removal of epidural catheters.


FIGURE 2:Safety algorithm for neuroaxial blockade in patients with intracranial space-occupying lesions. CSF = cerebrospinal fluid. (Reproduced with permission from Leffert LR, Schwamm LH: Neuraxial anesthesia in parturients with intracranial pathology: a comprehensive review and reassessment of risk. Anesthesiology.2013 Sep;119(3):703-718.)

The American Society of Regional Anesthesia and Pain Medicine periodically updates its guidelines for the initiation of regional anesthesia in patients receiving antithrombotic or thrombolytic therapy.62

Briefly, neuraxial techniques in patients receiving subcutaneous unfractionated heparin (UFH) with dosing regimens of 5000 U every 12 hours are considered safe (Table 12). The risks and benefits of thrice-daily UFH or more than 10,000 U daily should be assessed on an individual basis; vigilance should be maintained to detect new or worsening neurodeficits in this setting. For patients receiving heparin for more than 4 days, a platelet count should be assessed before neuraxial block or catheter removal due to concerns for heparin-induced thrombocytopenia (HIT). In patients who receive systemic heparinization, it is recommended to assess the activated plasma thromboplastin time (aPTT) and discontinue heparin for 2 to 4 hours prior to catheter manipulation or removal. Administration of intravenous heparin intraoperatively should be delayed for at least 1 hour after epidural placement; a delay before administration of subcutaneous heparin is not required. In cases of full heparinization for CPB, additional precautions include delaying surgery for 24 hours in the event of a traumatic tap, tightly controlling the heparin effect and reversal, and removing catheters when normal coagulation is restored.

Epidural blockade in patients taking aspirin and nonaspirin NSAIDs is considered safe, as the risk of epidural hematoma is low. Needle placement should be delayed for 12 hours in patients receiving low molecular weight heparin (LMWH) thromboprophylaxis and for 24 hours in those receiving therapeutic doses. It is recommended that warfarin be discontinued for several days prior to surgery and that the international normalized ratio (INR) return to baseline prior to initiation of epidural techniques. An INR below 1.5 is considered sufficient for catheter removal, although many clinicians may be comfortable manipulating catheters with higher INR values. Refer to Chapter 52 for more detailed information on these and newer agents. Neuraxial techniques are contraindicated in the setting of DIC, which may complicate sepsis, trauma, liver failure, placental abruption, amniotic fluid embolism, and massive transfusion, among other disease processes (Table 13). If DIC develops after epidural placement, the catheter should be removed once normal clotting parameters have been restored.

TABLE 12. Epidural blockade in patients receiving antithrombotic therapy.

NSAIDs (aspirin)

No contraindication


Wait 7 days before epidural placement

5000 U subcutaneous UFH every 12 hours

No contraindication

>10,000 U subcutaneous UFH daily

Safety not established

Intravenous heparin

Wait at least 60 minutes after instrumentation before administration of heparin; consider aPTT and wait 2–4 hours prior to catheter removal

LMWH thromboprophylactic dose

Wait 12 hours before epidural placement

LMWH therapeutic dose

Wait 24 hours before epidural placement


Wait for INR to normalize before neuraxial block; remove neuraxial catheter when INR < 1.5

INR = international normalized ratio; LMWH = low molecular weight heparin; NSAIDs = nonsteroidal anti-inflammatory drugs; UFH = unfractionated heparin.

TABLE 13. Conditions associated with disseminated intravascular coagulation.


Trauma (head injury, extensive soft tissue injury, fat embolism, massive hemorrhage)

Massive transfusion

Malignancy (pancreatic carcinoma, myeloproliferative disease)

Peripartum (amniotic fluid embolism, placental abruption, HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome, abnormal placentation)

Vascular disorders (aortic aneurysm, giant hemangioma)

Immunologic disorders (hemolytic transfusion reaction, transplant rejection, severe allergic reaction)

Liver failure

Thrombocytopenia and Other Common Bleeding Disorders

Thrombocytopenia, which may be caused by several pathologic conditions, is a relative contraindication to neuraxial anesthesia. While there is currently no universally accepted platelet count below which epidural placement should be avoided, many clinicians are comfortable with a platelet count above 70,000 mm 3 in the absence of clinical bleeding.63 The cutoff may be higher or lower, however, depending on the etiology of the thrombocytopenia, the bleeding history, the trend in platelet number, individual patient characteristics (eg, a known or suspected difficult airway), and provider expertise and comfort level. In general, platelet function is normal in conditions such as gestational thrombocytopenia and immune thrombocytopenic purpura (ITP).


The etiology of thrombocytopenia, the patient’s bleeding history, and the trend in platelet count must be taken into account when determining the safety of initiation of epidural blockade in thrombocytopenic patients. Certain conditions, such as ITP and gestational thrombocytopenia, are associated with functioning platelets despite a low platelet count.

A platelet count below 50,000 mm 3 in the setting of ITP may respond to corticosteroids or intravenous immunoglobulin (IVIG), when necessary. Functional platelet defects may be present in several less- common conditions, such as HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count); thrombotic thrombocytopenic purpura (TTP); and hemolytic uremic syndrome (HUS). Other conditions such as systemic lupus erythematous (SLE), antiphospholipid syndrome, type 2B von Willebrand disease (vWD), HIT, and DIC are associated with thrombocytopenia of varying degrees (Table 14).

A standard platelet count has not been established for catheter removal. While some sources suggest 60,000 mm3 is appropriate, catheter removal without adverse sequelae has been reported at counts below that cutoff.64 If platelet number or function is impaired after an epidural catheter has been placed, such as in the case of intraoperative DIC, the catheter should remain in situ until the coagulopathy has resolved.

Other common bleeding diatheses that comprise relative contraindications to the initiation of epidural blockade include hemophilia, vWD, and disorders related to lupus anticoagulants and anticardiolipin antibodies. Hemophilia A and B are X-linked diseases characterized by deficiencies in factors VIII and IX, respectively. Although specific guidelines are lacking, neuraxial procedures are considered safe in carriers of the dis- ease with normal factor levels and no bleeding complications. Neuraxial techniques have been performed without adverse sequelae in homozygous patients after factor replacement therapy once factor levels and the aPTT have normalized. Patients with lupus anticoagulants and anticardiolipin antibodies are predisposed to platelet aggregation, thrombocytopenia, and, because of interactions between antibodies and platelet membranes, thrombosis. As a result, many of these patients are anticoagulated with heparin in the peripartum or perioperative period. Heparin levels should be monitored with a blood heparin assay, thrombin time, or activated clotting test prior to performing neuraxial blockade. Of note, the aPTT is elevated at baseline in these patients and is likely to remain elevated after discontinuation of heparin due to interactions between the circulating antibodies and the coagulation tests.

Von Willebrand disease is the most common inherited bleeding disorder. It is characterized by either a quantitative (type 1 and type 3) or qualitative (type 2) deficiency in von Willebrand factor (vWF), a plasma glycoprotein that binds to and stabilizes factor VIII and mediates platelet adhesion at sites of vascular injury. The clinical presentation of vWD varies: Patients with type 1, the most common type, experience mucocutaneous bleeding, easy bruising, and menorrhagia; patients with type 2 vWD may experience moderate-to-severe bleeding and, in the case of type 2B, thrombocytopenia; type 3, which is rare, presents with severe bleeding, including hemarthroses (Table 15). Both treatment options and the decision to proceed with neuraxial blockade also vary with the different disease presentations. Type I responds to desmopressin (DDAVP), which promotes secretion of stored vWF from endothelial cells and results in a rapid rise in both plasma vWF and factor VIII. Factor VIII concentrates and cryoprecipitate are treatment options for type 2 and type 3 vWD. Specialized laboratory tests may help confirm the diagnosis and type of vWD but are not widely available; standard coagulation tests may serve to rule out other bleeding disorders. In addition to a thorough history and physical examination, collaboration with a hematologist and other team members, and a review of any pertinent laboratory results, a risk-benefit analysis should be performed prior to initiation of epidural procedures in patients with vWD.

TABLE 14. Causes of thrombocytopenia.


Idiopathic thrombocytopenic


Thrombotic thrombocytopenic purpura

Antiphospholipid syndrome Systemic lupus erythematosus


Gestational thrombocytopenia

Preeclampsia (HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome)

von Willebrand disease

Type 2B

Drug related

Heparin-induced thrombocytopenia

Methyldopa Sulfamethoxazole

Lymphoproliferative disorders

Hemolytic uremic syndrome

TABLE 15. Classification of von Willebrand disease.


Underlying disorder

Clinical Presentation/Characteristics


Deficient quantity of vWF

Mucocutaneous bleeding, epistaxis, easy bruising, menorrhagia


Defect in quality of vWF

Moderate bleeding


Abnormal vWF

Moderate bleeding; thrombocytopenia; risk of thrombosis


Abnormal vWF binding

Rare; significant bleeding


Inactive vWF binding sites

May see low factor VIII and normal vWF levels


Severe deficiency of vWF

Severe bleeding, hemarthroses, muscle hematomas

Preexisting Central Nervous System Disorders

Historically, the administration of neuraxial blockade has been contraindicated in patients with preexisting central nervous system (CNS) disease, including multiple sclerosis (MS), post-polio syndrome (PPS), and Guillain-Barré syndrome (GBS). In the case of MS, demyelinated nerves were thought to be more vulnerable to LA-induced neurotoxicity. An early study by Bader and colleagues suggested an association between MS relapse and higher concentrations of epidural LA among parturients,65 although a subsequent study in the same patient population failed to demonstrate an adverse effect of epidural anesthesia on either the rate of relapse or the progression of disease.66 A more recent retrospective study by Hebl and colleagues found no evidence of MS relapse after spinal or epidural anesthesia in 35 patients, 18 of whom received epidural blockade.67 While it is unlikely that epidural anesthesia and analgesia cause MS exacerbations, definitive studies on pharmacological properties of LAs in MS, optimal dosing regimens, and whether LAs interact directly with MS lesions are lacking.68 Until further data are available, it is reasonable to use low-concentration LAs and perform a thorough assessment and documentation of disease severity and neurologic status prior to initiation of central neuraxial blockade in patients with MS. These patients should also be informed of possible aggravation of symptoms, irrespective of anesthetic technique.

The decision to perform epidural anesthesia in patients with PPS, the most prevalent motor neuron disease in North America, requires careful analysis of the potential risks and benefits on a case-by- case basis. PPS is a late-onset manifestation of acute poliomyelitis infection that presents with fatigue, joint pain, and muscle atrophy in previously affected muscle groups. Epidural techniques in this patient population can be complicated by difficult puncture related to abnormal spinal anatomy, potential worsening of symptoms, and transient respiratory weakness. Alternatively, GA presents challenges related to sensitivity to muscle relaxants and sedatives and risks of respiratory compromise and aspiration. Although data are limited, there is no evidence that epidural techniques contribute to worsening of neurologic symptoms in patients with PPS.

Evidence linking epidural techniques to either activation or recurrence of GBS is also lacking. GBS presents with progressive motor weakness, ascending paralysis, and areflexia, most likely attributable to a postinfection inflammatory response. Older age at onset and severe initial disease are among the risk factors for prolonged neurologic dysfunction. Epidural anesthesia has been used successfully in patients with GBS, most commonly in obstetric patients, although exaggerated hemodynamic responses (hypotension and bradycardia), higher- than-normal spread of LAs, and worsening of neurologic symptoms have been reported.69 As always, a risk-benefit analysis is warranted prior to performance of epidural blockade in patients with GBS, as are assessment and documentation of neurologic examination of the patient and a thorough discussion of the risks of anesthesia. It is reasonable to avoid regional techniques during periods of acute neuronal inflammation.

Patients with spina bifida may also present a unique challenge to anesthesiologists. Spina bifida occulta occurs when the neural arch fails to close without herniation of the meninges or neural tissues. It is most commonly limited to one vertebra, although a small percentage of affected individuals have involvement of two or more vertebrae with associated neurologic abnormalities, underlying cord abnormalities, and scoliosis. In general, the use of epidural techniques is not contraindicated in patients with spina bifida occulta, although placement at the level of the occulta lesion, most commonly at L5 to S1, may have an increased risk of dural puncture and patchy or higher-than-normal response to LAs. In contrast, epidural placement in patients with spina bifida cystica has several potential risks, including risk of direct injury to the cord due to a low-lying conus medullaris, unpredictable or higher-than-expected spread of LAs, and increased risk of dural puncture.

Fever or Infection

Controversy exists regarding the administration of neuraxial anesthesia in febrile patients and in individuals infected with human immunodeficiency virus (HIV), herpes simplex virus type 2 (HSV-2), and varicella zoster virus (VZV). The use of regional anesthesia in the presence of a low-grade fever of infectious origin is controversial due to concerns of spreading the infectious agent to the epidural or subarachnoid space, with subsequent meningitis or epidural abscess formation. Fortunately, infectious complications of regional anesthesia are rare, and studies to date have failed to demonstrate a causal relationship between neuraxial procedures, with or without dural puncture, and subsequent neurologic complications. While no universal guidelines exist, available data suggest that fever does not preclude the safe administration of epidural anesthesia and analgesia. The anesthetic management of febrile patients should be based on an individual risk-benefit analysis. Whether general or regional anesthesia is chosen, antibiotic therapy should be either completed prior to or underway during initiation of the anesthetic. Adherence to strict aseptic techniques and postprocedure monitoring to detect and treat any complications are essential.

Historically, there have been concerns about the safety of neuraxial procedures in individuals infected with HIV due to both the theoretical risk of inoculation of the virus into the CNS and the possibility that neurologic manifestations of HIV may be attributed to the anesthetic technique.70 However, the CNS is infected early in the course of HIV infection, and there is no evidence that neuraxial instrumentation, including an epidural blood patch (EBP) for the treatment of PDPH, confers additional risk of viral spread to the CNS. There also is no evidence that the introduction of HIV- infected blood into the CSF might exacerbate a preexisting CNS infection, such as meningitis. Concerns that neurologic sequelae of HIV might be attributed to the neuraxial technique also appear to be unsubstantiated, as a temporal relationship between the epidural placement and the onset of neurologic deficits is unlikely. Nonetheless, thorough documentation of any preexisting neurologic deficit is recommended, given that neurologic complications of HIV are not uncommon and that HIV- positive individuals are at high risk for other sexually transmitted diseases that affect the CNS. Potential risks should be discussed in advance, and, as always, strict aseptic technique to protect both the patient and the anesthesiology provider must be maintained.

Areas of concern regarding the use of regional anesthesia in patients with HSV-2 include the risk of introducing the virus into the CNS during administration of neuraxial anesthesia; the possibility that a disseminated infection that develops after a regional anesthetic might be ascribed to the anesthetic itself, despite the lack of a causal relationship; and the safety of neuraxial techniques in primary HSV-2 outbreaks, which may be silent and difficult to distinguish from secondary outbreaks, but more commonly present with viremia, constitutional symptoms, genital lesions, and, in a small percentage of patients, aseptic meningitis. There are no documented cases of septic or neurologic complications following neuraxial procedures in patients with secondary (ie, recurrent) HSV infection; however, the safety of regional anesthesia in patients with primary infection has not been established. Crosby and colleagues conducted a 6-year retrospective analysis of 89 patients with secondary HSV infection who received epidural anesthesia for cesarean delivery and reported that no patients suffered septic or neurologic complications.71 Similarly, in their retrospective survey of 64 parturients with secondary HSV infection who received spinal, epidural, or GA for cesarean delivery, Bader et al reported no adverse outcomes related to the anesthetic.72 Based on the findings in these and other reported series, it appears safe to use spinal or epidural anesthesia in patients with secondary HSV infection. Pending more conclusive data, however, it seems prudent to avoid neur- axial blockade in patients with HSV-2 viremia.

Concerns also exist regarding the use of regional anesthesia in adults with either primary or recurrent VZV infections, such as herpes zoster (ie, shingles) and postherpetic neuralgia (PHN). However, neuraxial procedures, including epidural steroid injections, are not uncommonly used to treat acute herpes zoster, prevent PHN, and treat the pain associated with PHN, often in conjunction with antiviral therapy. The presence of active lesions at the site of injection is considered a contraindication to these and other neuraxial techniques. For the small subset of patients who are infected with primary VZV as adults, severe complications such as aseptic meningitis, encephalitis, and varicella pneumonia may result. The performance of regional anesthesia in this setting is more controversial but may be preferable to GA in some cases, primarily due to concerns for pneumonia.73 Ultimately, a careful risk-benefit analysis, in addition to assessment and documentation of any preexisting neurologic deficits, is recommended prior to initiation of neuraxial blockade in these patients.

Localized skin infection at the site of intended needle puncture is another relative contraindication to neuraxial blockade, primarily due to concerns that spinal epidural abscess (SEA) or meningitis may result. Hematogenous spread of a localized infection has been implicated in SEA, although a causal relationship is not clearly established in the reported cases. Maintenance of strict sterile precautions and a low index of suspicion in the presence of neurologic signs may minimize the risk. Needle insertion should be attempted after appropriate antibiotic administration, and a site remote from the localized infection is recommended.

Previous Back Surgery, Preexisting Neurologic Injury, and Back Pain

Traditionally, a history of previous back surgery was considered a relative contraindication to neuraxial blockade due to concerns for infection, exacerbation of preexisting neurologic deficits, and an increased likelihood of difficult or unsuccessful block. Technical difficulties may be related to degenerative changes above or below the level of fusion, adhesions in the epidural space, epidural space obliteration, dense scar tissue at the point of intended needle entry on the skin surface, the presence of graft material, and the presence of extensive rods that preclude identification of or access to midline. Despite these concerns, one large retrospective study of patients with a history of spinal stenosis, peripheral neuropathy, or lumbar radiculopathy found that previous spinal surgery did not affect the success rate or frequency of technical complications.74 In patients with metal rods (eg Harrington rods), anteroposterior and lateral radiographs or a copy of the operative report may help to identify the extent of instrumentation, as well as the presence of additional anatomic abnormalities. Ultrasound may aid in the identification of midline in challenging epidural cases. Potential complications, such as irregular, limited, or excessive cranial spread of LAs and an increased risk of PDPH if multiple attempts at placement are required, should be discussed with the patient during the informed consent process. Of note, similar technical difficulties encountered during the original technique can be expected during an EBP procedure. Because of these and other concerns, spinal anesthesia may be preferred, when appropriate, over epidural blockade.

Back pain is a ubiquitous problem that should not be considered a contraindication to neuraxial blockade and, rather, is a relatively common indication for epidural steroid and LA injections. One recent study found a higher than previously reported rate of new neurologic deficits and worsening of preexisting symptoms in patients with compressive radiculopathy or multiple neurologic disorders (spinal stenosis or lumbar disk disease) who received neuraxial anesthesia.74 However, a causal relation- ship was not clearly established. Many of the concerns regarding neuraxial procedures in patients with back pain can be addressed prior to initiation of neuraxial anesthesia with a thorough his- tory and physical examination; not uncommonly, the cause of back pain is not neurologic in origin. In these cases, regional techniques are not associated with new-onset back pain and are unlikely to exacerbate the pre-existing condition. Because patients with pre-existing neurologic conditions may be at increased risk of postoperative neurologic complications after neuraxial techniques, a careful risk-benefit analysis is warranted on a case-by-case basis. Pre-existing neurologic deficits or symptoms and their severity should be documented.

Preload-Dependent States

Traditionally, neuraxial blockade has been considered contraindicated in patients with severe aortic stenosis (AS) and other preload-dependent conditions, such as hypertrophic obstructive cardiomyopathy (asymmetric septal hypertrophy, ASH), due to the risk of acute decompensation in response to decreased systemic vascular resistance (SVR). The later stages of AS are associated with decreased diastolic compliance, impaired relaxation, increased myocardial oxygen demand, and decreased perfusion of the endocardium.75 Decreased SVR in the setting of either GA or neuraxial blockade leads to decreased coronary perfusion and contractility, with a further reduction in cardiac output (CO) and worsening hypotension. Bradycardia, tachycardia, and other dysrhythmias are also poorly tolerated. The current evidence regarding regional anesthesia in patients with AS is based on case reports and lacks the scientific validity provided by randomized controlled trials. However, it appears that carefully titrated CSE and continuous epidural and spinal techniques, most commonly with invasive monitoring, may be acceptable options for patients with AS. Single-shot spinal anesthetics are generally contraindicated, as gradual onset of sympathetic blockade is essential.

Anesthetic goals for patients with ASH are similar, with emphasis on maintaining preload, afterload, euvolemia, and vascular resistance, while avoiding tachycardia and enhanced contractility. Invasive monitoring and, if necessary, intermittent transthoracic echocardiography may help guide fluid and vasopressor requirements, as well as guide management in the event of acute decompensation.76

Epidural Placement in Anesthetized Patients

Initiation of epidural blockade in adults under GA is controversial due to concerns that these patients cannot respond to pain and may therefore be at increased risk for neurologic complications. Indeed, paresthesias during block performance and pain on LA injection have been identified as risk factors for serious neurologic deficits after regional techniques. Consequently, some experts consider close communication with the patient an essential component of safe epidural performance.77 Current data support the practice of epidural insertion in awake or minimally sedated patients, but needle and catheter placement in anesthetized adults may be an acceptable alternative in selected cases. Studies of lumbar epidural insertion while patients are undergoing GA have demonstrated that the risk of neurologic complications is small.78 Overall, the relative risk of administration of epidural blockade in anesthetized patients, compared with epidural placement in awake patients, is unknown due to the low overall incidence of serious neurologic complications associated with regional anesthesia.

Needle Insertion Through a Tattoo

Concerns that puncturing a tattoo during epidural placement may have adverse sequelae appear unsubstantiated in the literature. Theoretical risks are related primarily to the introduction of a potentially toxic or carcinogenic pigment into the epidural, subdural, or subarachnoid space. However, to date no significant complications related to inserting a needle through a tattoo have been reported in the literature, although potential long-term consequences cannot be dismissed.


An understanding of the anatomy of the vertebral column, spinal canal, epidural space and its contents, and commonly encountered anatomic variations among individuals is essential for the safe and effective initiation of epidural blockade. A three-dimensional mental image of vertebral column anatomy also aids in troubleshooting when identification of the epidural space is equivocal or when complications of epidural catheterization, such as unilateral blockade, intravascular cannulation, or catheter migration, occur. This section presents the basic anatomic considerations for successful epidural anesthesia and analgesia and reviews several controversies in the field of applied anatomy, including the accuracy of anatomic landmarks to estimate the spinous process level, the existence (or lack thereof ) of a subdural compartment, and the contents of the epidural space.


Vertebral Column General Appearance

Seven cervical, 12 thoracic, 5 lumbar, 5 fused sacral, and 3 to 5 (most commonly 4) fused coccygeal vertebrae comprise the vertebral column. The vertebral column is straight when viewed dorsally or ventrally. When viewed from the side, the cervical and lumbar regions are concave posteriorly (lordosis), and the thoracic and sacral regions are concave anteriorly (kyphosis) (Figure 3). The four physiologic spinal curves are fully developed by 10 years of age and become more pronounced during pregnancy and with aging. In the supine position, C5 and L3 are positioned at the highest points of the lordosis; the peaks of kyphosis occur at T5 to T7 and at S2.


C5 and L3 comprise the highest points of lordosis in the supine position; the highest points of kyphosis are T5 to T7 and S2.


FIGURE 3:Physiologic spinal curves: anterior, posterior and lateral views (left to right).

Structure of Vertebrae

With the exceptions of C1 and C2 and the fused sacral and coccygeal regions, the general structure of each vertebra consists of an anterior vertebral body (corpus, centrum) and a posterior bony arch. The arch is formed by the laminae; the pedicles, which extend from the posterolateral margins of the vertebral body; and the posterior surface of the vertebral body itself. In addition to the spinous processes, which are formed by the fusion of the laminae at midline, the vertebral arch supports three pairs of processes that emerge from the point where the laminae and pedicles join: two transverse processes, two superior articular processes, and two inferior articular processes. Adjacent vertebral arches enclose the vertebral canal and surround portions of the longitudinal spinal cord. The spinal canal communicates with the paravertebral space by way of gaps between the pedicles of successive vertebrae. These intervertebral foramina serve as passageways for the segmental nerves, arteries, and veins.

There is substantial variation in the size and shape of the vertebral bodies, the spinous processes, and the spinal canal at different levels of the vertebral column (Figure 4). C3 through C7 have the smallest vertebral bodies, while the spinal canal at this level is wide, measuring 25 mm. These cervical vertebrae, with the exception of C7, have short, bifurcated spinous processes. C7, the vertebra prominens, has a long, slender, and easily palpable horizontal spinous process protruding at the base of the neck that often serves as a surface landmark during epidural procedures. However, the first thoracic spinous process may be equally or more prominent than C7 in up to one-third of male individuals, as well as in thin patients and in patients with scoliosis and degenerative diseases.79 The vertebra prominens may also be difficult to distinguish from C6 in up to half of individuals, most commonly females.80

The thoracic vertebral bodies are larger than the cervical vertebral bodies and are wider in the posterior than anterior dimension, contributing to the characteristic thoracic curvature. The long and slender thoracic spinous processes, with tips that point caudally, are most sharply angled between T4 and T9, making insertion of the epidural needle in the midline more difficult in the midthoracic region. Beyond T10, they increasingly resemble those in the lumbar region. Each thoracic vertebra articulates with ribs along the dorsolateral border of its body, a feature that may help distinguish the lower thoracic and upper lumbar regions. The inferior angle of the scapula and the 12th rib are widely used in clinical practice to estimate the level of the spinous processes of T7 and T12, respectively. The imaginary line connecting the caudal-most margin of the 12th ribs is often presumed to cross the L1 spinous process (Table 16).

The lumbar vertebrae are the largest movable segments, with thicker anterior than posterior dimensions that contribute to the characteristic lumbar curvature. The spinous processes in this region are blunt and large, with tips that point posteriorly. Anatomic variations in the lumbosacral region that may have clinical implications are not uncommon. Sacralization of the last lumbar vertebra, marked by fusion of L5 to the sacral bone, and lumbarization of S1 and S2, in which fusion is incomplete, may make numbering and identification of the correct lumbar level difficult.81 Although probably not of clinical significance, patients with sacralization have also been found to have a higher position of the conus medullaris, which demarcates the cone-shaped terminus of the spinal cord, than those with lumbarization or without lumbosacral transitional vertebrae.82 In the absence of these transitional vertebrae, the largest and most easily palpable interspace corresponds to L5 to S1.

TABLE 16. Anatomic landmarks to identify vertebral levels.

Vertebra prominens


Root of spine of scapula


Inferior angle of scapula


Rib margin


Superior aspect of iliac crest


Posterior superior iliac spine



FIGURE 4: Size and shape of the vertebral bodies at different spinal levels.

Surface Anatomic Landmarks to Identify the Spinal Level

Surface landmarks are often used to identify the intended spinal level during initiation of epidural anesthesia (Figure 5). However, palpation and inspection of surface anatomical landmarks may fail to help localize the correct intervertebral space, particularly when considering individual variations in the vertebral level of these landmarks, the varying termination of the conus medullaris between the middle third of T12 and the upper third of L3,83 and anesthesiologists’ poor record of identifying the correct interspace.

Common pitfalls to using skeletal landmarks to identify the level of puncture include the following: The vertebra prominens is commonly confused with C6 and T1; the scapula may be difficult to identify during TEA placement in obese patients; tracing the vertebra attached to the 12th rib can be misleading, particularly in obese patients; and the line connecting the posterior superior iliac spines, often used to identify S2, commonly crosses the midline at variable levels between L5 and S1.84 Several studies have demonstrated that Tuffier’s line (also known as Jacoby’s line or the intercristal line), which joins the superior aspect of the iliac crests, may cross midline at least one, and perhaps two, levels higher than the predicted L4–L5 inter- space,85 particularly in pregnant,86 elderly, and obese patients.

Anesthesiologists have a poor record of estimating the correct interspace based on external landmarks. Van Gessel and colleagues found that the level of lumbar puncture is misidentified up to 59% of the time.87 In a more recent study, Broadbent and co-workers found that practitioners identify the correct lumbar level in only 29% of cases; the space is misidentified by two spinal levels, with the actual level higher than that predicted, in 14% of cases.88 Lirk et al confirmed the tendency of trained anesthetists to place the epidural needle more cranially than intended, most often within one interspace of the predicted level, also in the cervical and thoracic spinal column.89 Overall, given the importance of selecting the correct site of puncture, caution is advised when using surface anatomic landmarks to identify intervertebral spaces. The increasing reliance on ultrasound determination of the spinal level may decrease the incidence of complications related to misidentification of the intended interspace.


Joints and Ligaments of the Vertebral Column General

Adjacent vertebrae of the cervical, thoracic, and lumbar regions, excluding C1 and C2, are separated and cushioned by fibrocartilaginous intervertebral disks. The soft, elastic core of each disk, the nucleus pulposus, is composed primarily of water, as well as scattered elastic and reticular fibers. The fibrocartilaginous annulus fibrosis surrounds the nucleus pulposus and attaches the disks to the bodies of adjacent vertebrae. The disks, which account for up to one-quarter of the length of an adult vertebral column, lose their water content as we age, contributing to the shortening of the vertebral column, reducing their effectiveness as cushions, and rendering them more prone to injury, particularly in the lumbar region.

The articular processes arise at the junction between the pedicles and laminae. Superior and inferior articular processes project cranially and caudally, respectively, on both sides of each vertebra. The vertebral arches are connected by facet joints, which link the inferior articular processes of one vertebra with the superior articular processes of the more caudal vertebra. The facet joints are heavily innervated by the medial branch of the dorsal ramus of the spinal nerves. This innervation serves to direct contraction of muscle that moves the vertebral column.

The Longitudinal Ligaments

The anterior and posterior longitudinal ligaments support the vertebral column, binding the vertebral bodies and intervertebral disks together (Figure 6). The posterior longitudinal ligament, which forms the anterior wall of the vertebral canal, is less broad than its anterior counterpart and weakens with age and other degenerative processes. Clinically, disk herniation occurs primarily in the paramedian portion of the posterior disk, at weak points in the posterior longitudinal ligament. This area comprises the anterior epidural space, as opposed to the more clinically relevant posterior epidural space, and should not interfere with epidural needle placement.


Disk herniation occurs primarily at weak points in the posterior longitudinal ligament in an area that comprises the anterior epidural space, as opposed to the more clinically relevant posterior epidural space.

Nonetheless, thorough documentation of pre-existing pain and neurologic deficits in patients with known disk herniation is recommended prior to initiation of epidural anesthesia. Also of clinical relevance, a membranous lateral extension of the posterior longitudinal ligament may serve as a barrier to the spread of epidural solutions and appears to cordon the veins anterior to the dura away from the rest of the epidural space.90


A membranous lateral extension of the posterior longitudinal ligament appears to cordon off the veins in the anterolateral epidural space, where epidural vein puncture and catheter cannulation are more likely to occur.


FIGURE 5: Skeletal landmarks used to determine the level of epidural placement
FIGURE 6: Ligaments of the vertebral canal

The Supraspinous and Interspinous Ligaments

Several other ligaments that support the vertebral column serve as key anatomic landmarks during epidural needle placement. The supraspinous ligament connects the tips of the spinous processes from C7 to L5; above C7 and extending to the base of the skull, it is called the ligamentum nuchae. This relatively superficial, inextensible ligament is most prominent in the upper thoracic region and becomes thinner and less conspicuous toward the lower lumbar region.91 The interspinous ligament, directly anterior to the supraspinous ligament, traverses the space between adjacent spinous processes in a posterocranial direction. It is less developed in the cervical region, which may contribute to a false LOR during cervical epidural procedures.92 On histological examination, the interspinous ligament appears to have intermittent midline cavities filled with fat.

Both the supra- and interspinous ligaments are composed of collagenous fibers that make a characteristic “crunching” sound or distinct tactile sensation as the epidural needle advances. During initiation of epidural placement via the midline approach, these ligaments serve as appropriate sites to engage the needle, although some practitioners may engage the needle closer to the epidural space, in the ligamentum flavum. A “floppy” epidural needle that angles laterally prior to attach- ment of the LOR syringe may indicate an off-midline approach, away from the supra- or interspinous ligaments.

The Ligamentum Flavum

The ligamentum flavum connects the lamina of adjacent vertebrae from the inferior border of C2 to the superior border of S1. Laterally, it extends into the intervertebral foramina, where it joins the capsule of the articular process. Anteriorly, it limits the vertebral canal and forms the posterior border of the epidural space. At each spinal level, the right and left ligamentum flava join discontinuously in an acute angle with the opening oriented in the ventral direction, occasionally forming midline gaps filled with epidural fat.93 In contrast to the collagenous inter- and supraspinous ligaments, the ligamentum flavum comprises primarily thick, elastic fibers arranged longitudinally in a tight network. Areas of ossification of the ligamentum flavum occur at different levels of the vertebral canal and appear to be a normal variant. These bony spurs, which may contribute to pre-existing neurological symptoms and could potentially impede epidural needle advancement, are most commonly encountered in the lower thoracic region, between T9 and T11, and diminish in both frequency and size in the caudal and cranial directions.94

The ligamentum flavum has variable characteristics, many of which are disputed in the literature, at different vertebral levels. First, its thickness varies at different levels and, possibly, in different physiologic states, with a range of 1.5–3.0 mm in the cervical segment, 3.0–5.0 mm in the thoracic segment, 5.0–6.0 mm in the lumbar segment, and 2.0–6.0 mm in the caudal region (Table 17).95 In isolated pregnant patients, the ligamentum flavum has been reported to be as thick as 10 mm, presumably due to edema.96 Also of note, the flavum’s thickness varies within the interspace itself, with the caudal region being significantly thicker than the rostral.

TABLE 17. Thickness of the ligamentum avum at di erent vertebral levels.

Vertebral Level

Thickness (mm)










The ligamentum flavum varies in thickness at different spinal levels and is thickest in the lumbar region. Its thickness also varies within each interspace.

Clinically, these varying degrees of thickness may influence the risk of inadvertent dural puncture or determine whether injection of an anesthetic solution into the epidural space is possible with the skin infiltration needle.


FIGURE 7:Ligamentum flavum with different types of midline gaps

Another controversy concerns the incidence and location of gaps formed by the incomplete fusion of the right and left ligamentum flava. In their study of 52 human cadavers, Lirk and colleagues found that up to 74% of the flava in the cervical region are discontinuous at midline.97 These gaps vary in location, with some occupying the entire height of the ligamentum flavum between successive vertebral arches and others occupying the caudal third portion only (Figure 7). Veins connecting the posterior external and internal vertebral venous plexuses not uncommonly traverse the caudal portion of the gaps. In another cadaveric study, Lirk et al determined that thoracic midline gaps were less frequent than cervical gaps but more frequent than those in the lumbar region, with an incidence as high as 35.2% at T10 to T11.98 In cadaveric studies of the lumbar ligamentum flavum, gaps were found most commonly at L1 and L2 (22.2%) and decreased caudally (11.4% at L2 to L4; 9.3% at L4 to L5; 0% at L5 to S1).99 Clinically, these gaps may contribute to failure to identify the epidural space using the LOR technique at midline. The characteristic “pop” sound and tactile sensation conferred by penetration of the elastic fibers of the ligamentum flavum may be absent in the setting of a discontinuous ligamentous arch. The depth to the epidural space at midline may also be affected.


Ligamentum flavum midline gaps represent incomplete fusion of the right and left ligamentum flava. They are common in the cervical spine and decrease in frequency in the thoracic and lumbar regions. The variable thickness of the ligamentum flavum and the presence of midline gaps may contribute to failure to identify the epidural space.

The Spinal Canal General

The vertebrae serve primarily to support the weight of the head, neck, and trunk; transfer that weight to the lower limbs; and protect the contents of the spinal canal, including the spinal cord. An extension of the medulla oblongata, the spinal cord serves as the conduit between the CNS and the peripheral nerves via 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal) (Figure 8). The adult cord measures approximately 45 cm or 18 inches and has two regions of enlarged diameter at C2–T2 and at T9–L2, areas that correspond with the origin of the nerve supplies to the upper and lower extremities. However, its level of termination varies with age, as well as among individuals of similar age groups. As a result of a discrepancy in the pace of growth of the spinal cord and vertebral column during development, the spinal cord at birth ends at approximately L3. By 6–12 months of age, the level of termination parallels that of adults, most commonly at L1. Below the conus medullaris, the long dorsal and ventral roots of all the spinal nerves below L1 form a bundle known as the cauda equina, or horse’s tail. A collection of strands of neuron- free fibrous tissue enveloped in pia mater comprises the filum terminale and extends from the inferior tip of the conus medullaris to the second or third sacral vertebra.

Spinal Nerves

Spinal nerves are classified as mixed nerves because they contain both a sensory and a motor component and, in many cases, autonomic fibers. Each nerve forms from the fusion of dorsal (sensory) and ventral (somatic and visceral motor) nerve roots as they exit the vertebral canal distal to the dorsal root ganglia, which contain the cell bodies of sensory neurons on either side of the spinal cord and lie between the pedicles of adjacent vertebrae. In general, dorsal roots are larger and more easily blocked than ventral roots, a phenomenon that may be explained in part by the larger surface area for exposure to LAs provided by the bundled dorsal roots.

At the cervical level, the first pair of spinal nerves exits between the skull and C1. Subsequent cervical nerves continue to exit above the corresponding vertebra, assuming the name of the vertebra immediately following them. However, a transition occurs between the seventh cervical and first thoracic vertebrae, where an eighth pair of cervical nerves exits; thereafter, the spinal nerves exit below the corresponding vertebra and take the name of the vertebra immediately above. The spinal nerves divide into the anterior and posterior primary rami soon after they exit the intervertebral foramina. The anterior (ventral) rami supply the ventrolateral side of the trunk, structures of the body wall, and the limbs. The posterior (dorsal) primary rami innervate specific regions of the skin that resemble horizontal bands extending from the origin of each pair of spinal nerves, called dermatomes, and the muscles of the back.


FIGURE 8: Vertebral column with spinal nerves

Clinically, knowledge of dermatomes is essential when planning anesthetics to specific cutaneous regions (Figure 9), although anesthesia may not be conferred reliably to the underlying viscera due to a separate innervation, and there is significant overlap in spinal nerve innervation of adjacent dermatomes (Table 18).

An intricate relationship exists between the spinal nerves and the autonomic nervous system (Figure 10). Preganglionic sympathetic nerve fibers originate in the spinal cord from T1 to L2 and are blocked to varying degrees during epidural anesthesia. They exit the spinal cord with spinal nerves and form the sympathetic chain, which extends the entire length of the spinal column on the anterolateral aspects of the vertebral bodies. The chain gives rise to the stellate ganglion, splanchnic nerves, and the celiac plexus, among other things. There are potential benefits and marked drawbacks to epidural blockade of the sympathetic nervous system. TEA appears to increase GI mobility by blocking the sympathetic supply to the inferior mesenteric ganglia, thereby reducing the incidence of postoperative ileus. Epidural anesthesia may also block the systemic stress response to surgery, in part by blockade of the sympathetic nervous system. However, mid- to low-thoracic sympathetic blockade may be associated with dilation of the splanchnic vascular beds, a marked increase in venous capacitance, a decrease in preload to the right heart, and many of the other undesirable effects (see Physiologic Effects of Epidural Blockade).

Cranial and sacral components comprise the parasympathetic nervous system. The vagus nerve, in particular, provides parasympathetic innervation to a broad area, including the head, neck, the thoracic organs and parts of the digestive tract. Parasympathetic innervation of the bladder, the descending large intestine, and the rectum originate at spinal cord levels S2 to S4.


FIGURE 9: Distribution of dermatomes

TABLE 18. Surface landmark correlation to dermatomal level.

Level of Blockade

Anatomic Landmark




Fifth finger


Inner aspect of arm




Xiphoid process




Inguinal ligament


Lateral aspect of foot



Spinal Meninges

Spinal meninges cover the cord and nerve roots and are continuous with the cranial meninges that surround and protect the brain (Figure 11). The tough, predominantly collagenous outermost layer, the dura mater, encloses the CNS and provides localized points of attachment to the skull, sacrum, and vertebrae to anchor the spinal cord within the vertebral canal. Cranially, the spinal dura mater fuses with periosteum at the level of the foramen magnum; caudally, it fuses with elements of the filum terminale and contributes to formation of the coccygeal ligament; laterally, the dura mater surrounds nerve roots as they exit the intervertebral foramina. The dura mater touches the spinal canal in areas, but does not adhere to it except in pathologic conditions. It also confers both permeability and mechanical resistance to the dural sac, which terminates at S1 to S2 in adults and S3 to S4 in babies. The spinal nerve root cuffs, which have been postulated to play a role in the uptake of epidurally administered LAs, are lateral projections of both the dura mater and the underlying arachnoid lamina.100

The flexible arachnoid mater, the middle meningeal layer, is loosely attached to the inner aspect of the dura and encloses the spinal cord and surrounding CSF within the subarachnoid space. It is composed of layers of epithelial-like cells connected by tight and occluding junctions, which impart its low permeability. The cell layers of the arachnoid mater are oriented parallel to the long axis of the spinal cord (cephalocaudad), a finding that has led some investigators to claim that the architecture of the arachnoid mater, rather than the dura mater, accounts for the difference in headache rates between perpendicular and parallel insertions of beveled spinal needles.101 By virtue of its flexibility, the arachnoid mater may “tent” and resist puncture by an advancing needle during initiation of spinal or CSE anesthesia. A discontinuous subarachnoid septum (septum posticum) that stretches from the posterior spinal cord to the arachnoid may contribute to irregular spread of LAs in the subarachnoid space.

The innermost meningeal layer, the pia mater, closely invests the underlying spinal cord and its blood vessels, as well as nerve roots and blood vessels in the subarachnoid space, and appears to have fenestrated areas that may influence the transfer of LAs during subarachnoid blocks.102 Caudally, the pia mater continues from the inferior tip of the conus medullaris as the filum terminale and fuses into the sacrococcygeal ligament.

It is possible that a cavity can be created at the arachnoid-dura interface that may explain patchy or failed epidural blocks with higher-than-expected cephalad spread (so-called subdural blocks). Early research suggested that the subdural extra-arachnoid space comprised a true potential space, with serous fluid that permitted movement of the dura and arachnoid layers alongside each other. Blomberg used spinaloscopy in cadaver studies to demonstrate its existence in up to 66% of humans.103 However, recent evidence suggests that, unlike a potential space, this arachnoid-dura interface is an area prone to mechanical stress that shears open only after direct trauma, such as air or fluid injection.104 It is also possible that these clefts may actually occur between layers of arachnoid instead of between dural border cells at the arachnoid-dura interface. More information on spinal meninges and related structures are detailed in Chapter 6.


Clefts may form at the arachnoid-dura interface as a result of mechanical stress and direct trauma. Injection of a large volume of LA intended for the epidural space in this area may result in a subdural block.

Blood Supply

Vertebral and segmental arteries supply the spinal cord. A single anterior spinal artery and two posterior spinal arteries, and their offshoots, arise from the vertebral arteries and supply the anterior two-thirds of the spinal cord and the remainder of the cord, respectively (Figure 12). The anterior artery is thin at the midthoracic level of the spinal cord, an area that also has limited collateral blood supply. Segmental arteries, which emerge from branches of the cervical and iliac arteries, among others, spread along the entire length of the spinal cord and anastomose with the anterior and posterior arteries. The artery of Adamkiewicz is among the largest segmental arteries and is most commonly unilateral, arising from the left side of the aorta between T8 and L1. With regard to the venous system, anterior and posterior spinal veins, which anastomose with the internal vertebral plexus in the epidural space, drain into the azygos, the hemiazygos, and internal iliac veins, among other segmental veins, via intervertebral veins. The internal vertebral venous plexus consists of two anterior and two posterior longitudinal vessels with a variable distribution and is postulated to be involved in bloody or traumatic epidural needle and catheter placements.105

Epidural Space

The epidural space surrounds the dura mater circumferentially and extends from the foramen magnum to the sacrococcygeal ligament. The space is bound posteriorly by the ligamentum flavum, laterally by the pedicles and the intervertebral foramina, and anteriorly by the posterior longitudinal ligament. Of the three epidural space compartments (posterior, lateral, and anterior), the posterior epidural space is most relevant clinically. The epidural space in general contains adipose tissue, blood vessels, nerve roots, and loose connective tissue in a nonuniform distribution. The veins in the space are continuous with the iliac vessels in the pelvis and the azygos system in the abdominal and thoracic body walls. Because the plexus is valveless, blood from any of the connected systems can flow into the epidural vessels. In contrast to traditional dogma, these vessels are located primarily in the anterior epidural space, where they are largely confined by the membranous extension of the posterior longitudinal ligament 106 (Figure 13). This area is probably a common site of epidural catheter blood vessel puncture. Also of clinical significance, the subatmospheric pressure of the epidural space diminishes significantly in the lumbar region, potentially affecting both the hanging- drop and the epidural pressure waveform techniques of identification of the epidural space.

The contents of the epidural space and their clinical implications have been debated extensively in the literature. The amount of adipose tissue in the epidural space appears to affect the spread of LA, but it remains unclear whether epidural fat prolongs block duration by serving as a reservoir or decreases the amount of available drug, thereby slowing onset, or both.107 The reduction of adipose tissue with age is speculated to account in part for the higher levels and faster onset of epidural anesthesia in the elderly.108 Similarly, the increase in adipose tissue in the lower lumbar area where the dural sac tapers may contribute to the variable effects of LA injections below L4–L5. Finally, adipose tissue in the midline gap, where the ligamentum flava fuse, may alter the tactile sensation that is normally appreciated during the LOR technique. Another anatomic controversy of the epidural space concerns whether septae, alternately described as sparse strands and as a continuous membrane that attaches the dura to the ligamentum flavum,109 obstruct catheter advancement, affect the spread and onset of LAs, and contribute to unilateral blocks and unintentional dural punctures. However, these septae have more recently been identified as an artifact of the midline posterior epidural fat pad.110 These fatty midline attachments do not appear to have a clinically significant effect on the spread of LAs.106 Rather, Hogan has postulated that the distribution of solution is non- uniform and directed among paths between structures in the epidural space according to differential pressures.111


FIGURE 10: Sympathetic nervous system.


FIGURE 11: Spinal meninges.


FIGURE 12: Sympathetic nervous system.


FIGURE 13: Epidural vein distribution in the lumbar region.

Distance From Skin to Epidural Space

The distance from the skin to the epidural space varies at different levels of the vertebral column. In the cervical region, Han and colleagues found that the average skin-to-epidural space depth (via the midline approach) was shallowest at C5 and C6 and increased in the caudal direction.92 Fujinaka et al noted that it is difficult to predict the actual depth of the cervical epidural space based on clinical characteristics.112 In contrast, Aldrete and coworkers, using magnetic resonance imaging (MRI) to measure the depth from the skin to the inner ligamentum flavum, noted the greatest depth at the C6-to-T1 levels, with a mean of 5.7 cm, possibly due to the presence of fatty tissue (the so-called hump pad) in the area.113 The depth to space in the midthoracic region from midline is influenced primarily by the sharp caudal angle of the spinous processes. As a result of the steep angle and bony impediments in this region, the paramedian approach is often preferred for midthoracic epidural placement.

Several studies have sought to measure the depth to the epidural space at the lumbar level. Studies of parturients show a range of depth from skin to space of 2 to 9 cm, with 89% in the range of 3.5–7.5 cm.114 In their search for a multivariate model to predict the distance in an obstetric population, Segal and col- leagues confirmed previously reported associations between increased weight and increased depth, as well as between oriental race and shallower spaces, with no independent association between race and depth after controlling for weight.114 In an earlier study, Sutton and Linter recorded that the skin to extradural space in 3011 parturients was 4 to 6 cm in 76% of the study participants.115 Patients with a shallow depth of 2 to 4 cm, comprising 16% of the study population, were found to be at a threefold higher risk of unintentional dural puncture. Of note, the shallow depth falls within the range of length of the LA infiltration needle. Overall, estimates of the depth to epidural space cannot be applied to the population at large, as independent variables, such as degree of flexion, patient positioning, dimpling and edema at the skin and subcutaneous tissue, and the angle of needle insertion, among other things, are difficult to quantitate and control. In the near future, routine ultrasound determination of depth to space on an individual basis prior to or during epidural needle placement might provide the most reliable means of diminishing the risk of inadvertent dural puncture and other complications of epidural anesthesia. Fluoroscopy is most appropriate in the cervical region, where spinal cord injury, total spinal anesthesia, and intra-arterial injection are among the possible complications.

The variable depth of the posterior epidural space is another clinically relevant measure that may influence the incidence of inadvertent dural puncture. The posterior epidural space viewed in the midline sagittal plane has been described as sawtoothed, characterizing its segmented shape.116 While studies are conflicting, at each segmental level, the depth of the posterior epidural space appears shallower at the caudal end. These variations notwithstanding, the distance between the ligamentum flavum and the dura is typically estimated as 7 mm, with a broad range from 2 mm to cm.106 This anterior-posterior distance is largest in the lumbar region, at L3–L4, decreases in the thoracic region, and is absent in the cervical region.117

Physiologic effects of epidural blockade

Epidural blockade provides surgical anesthesia, intraoperative muscle relaxation, and intrapartum and postoperative pain relief with widespread direct and indirect effects on several physiologic systems. The extent of these physiologic effects depends on the level of placement and the number of spinal segments blocked. In general, high thoracic epidural blocks (ie, above T5) and extensive epidural blocks are associated with more profound physiologic changes than blocks with low sensory levels (ie, below T10). This section reviews the physiologic alterations related to epidural anesthesia and analgesia.

Differential Blockade


Differential blockade occurs when sensory, motor, and sympathetic nerve functions are obtunded at different rates and to different degrees. It may be observed at both onset and regression of the block. In general, sympathetic blockade, which is not uncommonly incomplete, extends two to six dermatomes higher than sensory blockade, which in turn is higher than the motor blockade. Sensory blockade also occurs with a lower concentration or total dose of LA and develops faster than motor blockade. Among sensory functions, temperature is blocked first, followed by pinprick and, finally, touch. Although the mechanism of differential blockade has not been fully elucidated, it may be attributed to anatomic features of blocked nerves (eg, diameter and presence or absence of myelin), the length of blocked nervous tissue (a minimal length of blocked nerve is required for effective neuronal blockade), differences in nerve lipid membrane and ion channel composition, concurrent axonal activity during block onset, and LA type and concentration. These and several other mechanisms may collectively contribute to differential blockade.

Central Nervous System Effects


Cerebral blood flow (CBF) is autoregulated and is not affected by epidural blockade unless the patient experiences pronounced hypotension. However, neuraxial anesthesia does appear to have a sedative effect and to reduce anesthetic requirements for several agents, including midazolam, propofol, thiopental, fentanyl, and volatile agents. The degree of sedation and minimum alveolar concentration (MAC) sparing effect appear to correlate with the height and level of the sensory block; blockade of the middle thoracic dermatomes is associated with greater sedative effects than blockade of the lower lumbar segments.118 Although data are conflicting, higher-concentration LAs may contribute to a greater MAC-sparing effect.119 The addition of opioid adjuvants, such as morphine, to the epidural LA solution does not appear to reduce volatile agent requirements any further, although it does contribute to better postoperative pain scores.120 Overall, decreased anesthetic requirements have most commonly been attributed to decreased afferent input induced by the neuraxial block rather than to systemic effects of LAs, altered pharmacokinetics, or direct action of LAs on the brain.121

Several studies have demonstrated reduced hypnotic and anesthetic requirements after central neuraxial blockade. In an early study of 53 American Society of Anesthesiologists (ASA) physical status I and II adult males, Tverskoy and colleagues determined that subarachnoid bupivacaine blockade decreased hypnotic requirements for both midazolam and thiopental.122 A study that followed, also in ASA physical status I and II patients, determined that epidural bupivacaine profoundly decreased midazolam hypnotic requirements.123 Similarly, in a small prospective, randomized, double-blind, placebo-controlled trial, Hodgson and colleagues found that lidocaine epidural anesthesia reduced the MAC of sevoflurane by up to 50%.124 More recently, epidural bupivacaine administered via the caudal route has been shown to have a sparing effect on both intravenous fentanyl and sevoflurane requirements during orthopedic surgery in children.125

Cardiovascular and Hemodynamic Effects


Cardiovascular changes associated with epidural anesthesia and analgesia result primarily from blockade of sympathetic nerve fiber conduction. These changes include venous and arterial vasodilation, reduced SVR, changes in chronotropy and inotropy, and associated alterations in blood pressure and CO. The type and intensity of these changes are related to the level of block, the total number of dermatomes blocked, and, relatedly, the type and dose of LA administered. In general, lumbar epidural or low thoracic blocks are not associated with significant hemodynamic changes, while higher thoracic blocks (particularly those involving the T1–T4 sympathetic fibers) can cause more marked changes, not all of which are detrimental. However, factors such as pregnancy, age, comorbidities, patient positioning, and hypovolemia can complicate the clinical scenario and the anticipated cardiovascular effects.


Hypotension associated with neuraxial blockade results primarily from vasodilation and increased vascular bed capacitance.126 Both direct inhibition of the sympathetic outflow to the nerves innervating the blood vessels and a decrease in endogenous catecholamine release from the adrenal glands contribute to arterial and venous vasodilation. In general, arteriolar smooth muscle maintains autonomous tone, even in the setting of complete sympathectomy, while veins and venules dilate maximally. However, a degree of arteriolar vasodilation does occur. The venodilatory effect also predominates because of the large amount of blood in the venous system compared to the arterial system.

The degree of hypotension associated with epidural blockade correlates with the sensory level. For example, a more marked increase in venous capacitance occurs with blockade of the sympathetic outflow to the splanchnic veins (T6 to L1) due to dilation of the extensive splanchnic bed. With low epidural blocks, vasoconstriction of unblocked areas and release of catecholamines from the adrenal medullary system partially compensate for venous and arteriolar pooling and reductions in mean arterial pressure.127 Overall, healthy, normovolemic patients experience a nominal decrease in peripheral resistance and blood pressure during initiation and maintenance of epidural blockade.

Risk factors for appreciable hypotension during neuraxial anesthesia include sensory level above T5, low baseline pressure, increasing age, and combined general-neuraxial anesthesia. Severely hypovolemic patients and cardiac-compromised patients are also more likely to experience significant hypotension requiring vasopressor and inotropic support. Hypotension occurs more commonly with spinals than with epidurals, despite equivalent degrees of sympathetic blockade.

Heart Rate and Cardiac Function

In general, changes in heart rate and ventricular function vary with level of blockade, with more pronounced changes as the level increases. When the cardiac sympathetic fibers from T1 to T4 are blocked, decreased cardiac contractility and bradycardia ensue, resulting in decreased CO. Bradycardia also results from the decreased atrial stretch receptor activity attributed to decreased right atrial pressure. Venous pooling also contributes to the reduction in CO, particularly with higher blocks. Missant et al studied the effects of epidural anesthesia on left and right ventricular function in a pig model and found that lumbar epidural anesthesia reduced SVR without affecting left or right ventricular function.128 However, TEA reduced left ventricular contractility and minimally reduced SVR, while pre- serving right ventricular function.

Neuraxial blockade appears to have certain beneficial effects on the cardiovascular system, such as improved myocardial blood flow and myocardial oxygen balance. Tissue oxygenation has been observed to improve with high TEA under certain circumstances, particularly with intravenous fluid administration.129,130 TEA also appears to have antianginal effects,131,132 improve coronary perfusion,20 and improve recovery from reversible myocardial ischemia.133,134 Whether this results in improved perioperative cardiac outcome following major cardiac or thoracic surgery, however, is the subject of ongoing debate.135 Several authors have hypothesized that TEA may also protect against postoperative arrhythmias and atrial fibrillation after major cardiac and thoracic surgeries. However, data are conflicting. Svircevic et al performed a meta-analysis comparing GA and TEA for cardiac surgery and noted fewer postoperative supraventricular arrhythmias.136 However, Gu et al, in another recent meta-analysis, could not support such an effect.137

Pulmonary Effects


The motor and sympathetic changes associated with epidural anesthesia may affect lung function, depending on the level of blockade. In general, tidal volume remains unchanged even during high neuraxial blocks, while vital capacity may be reduced due to the decrease in expiratory reserve volume that occurs as accessory muscles involved in expiration are blocked. The ability to cough and clear respiratory secretions may also be impaired, particularly in patients with severely compromised respiratory function at baseline. However, inspiratory muscle function is unaffected and should remain sufficient to provide adequate ventilatory function.

Higher sensory levels may result in more marked changes in lung function. In a sentinel study, Freund et al inserted a lumbar epidural catheter and administered a mean volume of 20 mL of 2% lidocaine.138 An extensive block to T4 was achieved, but the decrease in vital capacity was minimal. However, catheter insertion at higher levels, with concomitant higher spread of LA, results in more pronounced pulmonary derangement.139 In contrast, when TEA is used postoperatively, a net positive effect on lung function can be observed, most likely because the enhanced pain relief prevents splinting. In a recent review article, Lirk and Hollmann determined the role of TEA and con- firmed the benefits in major abdominal and thoracic surgery.140

The rare occurrence of respiratory arrest after high epidural or spinal blockade can be attributed to hypoperfusion of the respiratory center in the brainstem rather than to direct LA effects on either the phrenic nerve or the CNS.

Gastrointestinal Effects


The sympathetic outflow to the GI tract arises from T5 to T12, while parasympathetic innervation is supplied by the vagus nerve. Sympathectomy associated with epidural blockade in the mid- to low- thoracic levels results in unopposed vagal tone, which manifests clinically with increased peristalsis, relaxed sphincters, an increase in GI secretions, and, likely, more rapid restoration of GI motility in the postoperative phase. Nausea and vomiting commonly accompany hyperperistalsis and can be treated effectively with intravenous atropine. Theoretically, increased intestinal motility could contribute to breakdown of surgical anastomoses, but this has not been demonstrated in the literature. Rather, TEA may decrease the risk of anastomotic leakage and improve perioperative intestinal perfusion, although the data are somewhat conflicting. Numerous experimental and clinical studies have demonstrated that TEA protects against splanchnic hypoperfusion and reduces postoperative ileus.141 However, similar benefits are not seen with lumbar epidural anesthesia.141

Renal/Genitourinary Effects


Because renal blood flow (RBF) is maintained through autoregulation, epidural anesthesia has little effect on renal function in healthy individuals. Compensatory and feedback mechanisms (afferent arteriolar dilation and efferent arteriolar vasoconstriction) ensure constant RBF over a broad range of pressures (50–150 mm Hg). During transient periods of hypotension below 50 mm Hg, oxygen delivery to the kidneys is adequately maintained.

Neuraxial blockade at the lumbar level has been postulated to impair control of bladder function secondary to blockade of the S2–S4 nerve roots, which carry the sympathetic and parasympathetic nerves that innervate the bladder. Urinary retention may occur until the block wears off. The clinician should avoid administering an excessive volume of intravenous fluids if a urinary catheter is not in place.

Neuroendocrine Effects


Surgical stress produces a variety of changes in the host’s humoral and immune response. Increased protein catabolism and oxygen consumption are common. Increased plasma concentrations of catecholamines, vasopressin, growth hormone, renin, angiotensin, cortisol, glucose, antidiuretic hormone, and thyroid-stimulating hormone have been documented after sympathetic stimulation associated with both minimally invasive and major open surgery. Perioperative manifestations of the surgical stress response may include HTN, tachycardia, hyperglycemia, suppressed immune function, and altered renal function. Increased catecholamine levels can also cause increased left ventricular afterload and, in combination with other pathologic responses to stress (eg, proinflammatory responses that may lead to plaque instability via activation of matrix metalloproteinase; raised corticotropin-releasing hormone levels that reduce cardiac nitric oxide release, increase endothelin production, and aggravate coronary endothelial dysfunction), trigger acute coronary syndromes and myocardial infarctions in patients with coexisting cardiac disease. Afferent sensory information from the surgical site is thought to play a pivotal role in this response.

The surgical stress response can be influenced by sympathetic blockade during epidural anesthesia and analgesia. The mechanisms involved are unresolved but most likely include both direct blockade of afferent and efferent signals during surgical stress and direct effects of LA agents. Brodner et al demonstrated that TEA combined with GA resulted in a reduced surgical stress response when compared to GA alone.142

The most critical effect of neuroendocrine activation in the perioperative period is the increase in plasma norepinephrine, which peaks roughly 18 hours after the surgical stimulus is initiated. The increase in plasma norepinephrine is associated with activation of nitric oxide in the endothelium of patients with atherosclerotic disease, producing paradoxical vasospasm. Thus, in patients with significant atherosclerotic disease, the combination of vasospasm and a hypercoagulable state may be the factors modulated by the cardioprotective effects of TEA. Indeed, studies indicated that coronary artery blood flow is improved with TEA.20



Hypothermia has significant side effects, such as increased cardiac morbidity, impaired coagulation, increased blood loss, and increased risk for infection. The rate and severity of hypothermia associated with epidural anesthesia is similar to that observed during cases under GA.143 Hypothermia associated with neuraxial anesthesia is primarily due to peripheral vasodilation resulting in heat redistribution from the core to the periphery.144 In addition, reduced heat production (due to reduced metabolic activity) results in a negative heat balance due to unchanged heat loss. Finally, thermoregulatory control is impaired. Of note, rewarming with forced air warming devices occurs more rapidly with neuraxial anesthesia as compared to GA due to peripheral vasodilation.145

Coagulation System


The postoperative period is a marked hypercoagulable state. Neuraxial blockade is associated with a decreased risk of DVT Epidural Anesthesia and Analgesia and pulmonary embolism, as well as a decreased risk of arterial and venous thrombosis.

Pharmacology of Epidural Blockade

An understanding of the physiology of nerve conduction and the pharmacology of LAs is essential for successful epidural blockade. Potency and duration of LAs, preferential blockade of sensory and motor fibers, and the anticipated duration of surgery or need for postoperative analgesia are factors that should be considered before initiating epidural blockade. This section covers several practical aspects of attaining effective epidural anesthesia and analgesia.

Epidural solutions may contain an LA with or without an adjuvant drug. Dose, volume, and concentration, as well as site of injection, of the LA solution vary, resulting in different pharmacodynamic effects. A, B, and C nerve fibers vary in size and in the presence of a myelin sheath. A-delta and C fibers are responsible for temperature and pain transmission. B fibers are autonomic fibers. The larger A fibers (especially A-alpha fibers) are motor fibers. C fibers are unmyelinated and smallest in size. Because they lack a protective myelin sheath and diffusion barrier, they are blocked rapidly. A and B fibers are myelinated and larger in size than C fibers. B fibers are responsible for autonomic nervous system transmission. They are smaller in size than A-delta fibers, but larger than C fibers. It is widely accepted that autonomic fibers are more susceptible to LA block than sensory fibers. Epidurally administered LA preferentially blocks sympathetic neural function; this explains the more extensive sympathetic dermatomal blockade when compared with sensory and motor blocks.146,147,148,149 However, Ginosar et al recently suggested that sensory function was more susceptible to blockade than sympathetic function.150 Several other studies concurred.151,152 The dose and concentration of LA used may account for the different findings in these studies. Because of their thick myelin sheath, motor fibers require much more LA and much more time before an adequate block is achieved.

Local anesthetics produce reversible nerve blockade by blocking sodium passage through the nerve membrane. When LA is injected into the epidural space, several things occur. Most of the injected LA is absorbed into the venous blood, and a large part is retained in epidural fatty tissue. The primary sites of action of an epidurally administered LA are the ventral and dorsal nerve roots that pass through the epidural space. However, based on studies using labeled LAs, LAs can cross the dura and penetrate the spinal cord, but to a lesser extent than their penetration into the spinal nerve roots.153 The segmental nerve roots are mixed sensory, motor, and sympathetic nerve fibers. Hence, all three types of fibers will be affected (to varying degrees).

Choice of Local Anesthetics


Drugs used for epidural blockade can be categorized into short-, intermediate-, and long-acting LAs. Onset of epidural blockade in the dermatomes immediately surrounding the site of injection can usually be detected within 5 or 10 minutes, if not sooner. The time to peak effect varies with the type of LA and the dose/volume administered (Table 19).

TABLE 19. Commonly used local anesthetics for epidural anesthesia and analgesia.


Concentration (%)

Onset Time (min)

Duration (min)





















The shortest-acting LA for neuraxial blockade is chloroprocaine, an ester. In the past, chloroprocaine was associated with adhesive arachnoiditis when large volumes were accidentally administered into the subarachnoid space.154 In addition, severe back pain was not uncommonly reported when large volumes were administered in the epidural space, most likely due to the ethylenediaminetetraacetic acid (EDTA) and bisulfite preservatives in the solution. Since 1996, preservative-free chloroprocaine has been available and has not been associated with either neurotoxic effects or back pain. In ambulatory settings and for emergency cesarean deliveries with in situ epidurals, chloroprocaine can provide excellent surgical anesthesia quickly, without delaying recovery room discharge. Delivered via the epidural route, 2% lidocaine is an intermediate-acting LA commonly used for surgical anesthesia. When epinephrine is added to the solution (1:200,000), it prolongs the duration of action by up to 60%.

Long-acting LAs used for epidural blockade are bupivacaine, levobupivacaine (no longer available in the United States), and ropivacaine. Dilute concentrations (eg, 0.1% to 0.25%) can be used for analgesia, while higher concentrations (eg, 0.5%) may be more appropriate for surgical anesthesia. The addition of epinephrine to these solutions can prolong the duration of action, although this effect is less reliable with long- versus intermediate-acting agents. Severe cardiotoxic reactions (hypotension, atrioventricular block, ventricular fibrillation, and torsades de pointes) refractory to usual resuscitation methods can result from accidental intravascular injection of bupivacaine. The rationale for the resistance to resuscitative measures lies in its high degree of protein binding and more pronounced effect on cardiac sodium channel blockade.155,156 Levobupivacaine, the S-enantiomer of bupivacaine, has a similar profile to bupivacaine but with less-pronounced cardiotoxic effects. Ropivacaine, a mepivacaine analogue, has a similar profile of action to bupivacaine. In most studies, Ropivacaine has demonstrated a slightly shorter duration of action than bupivacaine, potentially with a less-dense motor block at equipotent doses. A deterrent to the broader use of ropivacaine in clinical practice is its higher cost.157,158

Onset and Duration of Local Anesthetics


Alkalinization of the LAs, which are marketed in a water-soluble, ionized state, hastens onset. By increasing the concentration of the nonionized form, more lipid-soluble LA is available to penetrate the neural sheath and nerve membrane. Adding sodium bicarbonate immediately before injection of lidocaine, mepivacaine, or chloroprocaine produces a clinically significant faster onset of anesthesia and may also contribute to a denser block.159 However, ropivacaine and bupivacaine will precipitate with the addition of bicarbonate unless a very low concentration is used. Combining short- and long- acting drugs for rapid onset and a prolonged sensory block has not been proven to be effective. For example, mixing 2-chloroprocaine with bupivacaine for the rapid onset of the former and long duration of the latter results in shortening the duration and effectiveness of the bupivacaine.160 Continuous drug administration and the use of additives obviate the need for mixing LAs.


Combining short- and intermediate- or long-acting LAs for rapid onset with prolonged duration of action has not been proven to be effective. Continuous drug administration and the use of additives obviate the need for mixing LAs.

Adding epinephrine to certain LAs can increase the duration of action, most likely by decreasing vascular absorption. The effect is greatest with 2-chloroprocaine, lidocaine, and mepivacaine and is less effective with the longer-acting agents. Other vasoconstrictors, such as phenylephrine, have not been proven to be as effective in reducing the peak blood levels of LAs as epinephrine.161

Adjuvants to Local Anesthetics in the Epidural Space


A variety of other classes of drugs have been studied more recently to try to improve the quality of neuraxial blockade. In addition to several opioids (eg, fentanyl, sufentanil, and preparations of morphine); α-adrenergic agonists; cholinesterase inhibitors; semisynthetic opioid agonist- antagonists; ketamine; and midazolam have been studied, with mixed results.

The administration of clonidine in the epidural space has been studied extensively. An α2-adrenergic agonist, clonidine appears to prolong the duration of action of LAs, although the mechanism remains unclear. Animal studies have shown that clonidine reduces regional spinal cord blood flow, therefore slowing the rate of drug elimination.162 Kroin and colleagues demonstrated that the mechanism by which clonidine prolongs the duration of a block when mixed with LAs is not mediated by α-adrenoreceptors; rather, it is more likely related to the hyperpolarization-activated cation current Ih.163 Some of the potential benefits of the administration of clonidine in the epidural space may include the following:

  1. Prolongation and enhancement of the effects of epidural LAs without an additional risk of hypotension

  2. Reduction in LA dose requirements for labor epidural analgesia164,165

  3. Effective analgesia without motor impairment162

  4. Synergistic effect with opioids and opioid

  5. Modulation of the stress response to thoracic surgery166

  6. Preservation of lung function after thoracotomy167

  7. Possible reduction in cytokine response, further reducing
    pain sensitivity168

Side effects that are commonly associated with epidural
clonidine include dose-independent hypotension, bradycardia, sedation, and dry mouth. Combining clonidine with other agents, such as opioids, anticholinergics, opioid agonist-antagonists, and ketamine, may enhance the beneficial effects of these drugs while minimizing adverse side effects.169,170

Neostigmine, a cholinesterase inhibitor, is a more recent addition to the list of epidural additives for selective analgesia. The mechanism of action for its analgesic effect appears to be the inhibition of the breakdown of acetylcholine and the indirect stimulation of muscarinic and nicotinic receptors in the spinal cord. Although experience with epidural neostigmine is limited, it has been reported to provide postoperative pain relief without inducing respiratory depression, motor impairment, or hypotension.169 When combined with other opioids, clonidine, and LAs, it may provide benefits similar to clonidine without the side-effect profile of any of these drugs given alone.171,172,173 Observations in patients with cancer pain showed promise that its use might be associated with less nausea and vomiting than the intrathecal application.174 In an investigation randomizing 48 patients to receive 0, 1, 2, or 4 µg/kg of epidural neostigmine in addition to a bupivacaine spinal anesthetic for minor knee surgery, no case of intraoperative nausea or vomiting was observed, and postoperative nausea scores did not differ between groups.175 These results need to be corroborated by further studies before epidural neostigmine can be recommended for daily practice.

Other agents, such as ketamine, tramadol, droperidol, and midazolam, have been considered for epidural administration, with mixed results. Considerable controversy surrounds the use of midazolam intrathecally. Despite multiple publications recommending its use,176,177,178 recent studies have demonstrated that even a single dose of intrathecal midazolam may have neurotoxic effects. 179Until its safety profile can be ensured in human subjects, it is not recommended for neuraxial use at this time.180

One agent that shows promise is the extended-release formulation of one of the oldest opioids, morphine. DepoDurc, the brand name for extended-release epidural morphine, uses a drug-release delivery system called DepoFoamc. DepoFoamc is composed of microscopic lipid-based particles with internal vesicles that contain the active drug and slowly release it. Recent studies have demonstrated effective pain relief with relatively minor side effects for up to 48 hours when appropriately dosed.181,182,183 However, concerns about delayed respiratory depression have limited its clinical use in this early stage of its clinical use.


Other Factors Affecting Epidural Blockade Injection Site

The epidural blockade is most effective when the block or the catheter is inserted in a location that corresponds to the dermatomes covered by the surgical incision. The most rapid onset and the densest block occur at the site of injection. By inserting the catheter closer to the dermatomal distribution of the surgical site, a lower dose of drug can be given, thereby reducing side effects.184,185 This concept is especially important when thoracic epidural analgesia is used for postoperative analgesia.

After lumbar epidural injection, the analgesic and anesthetic effects spread to a greater degree cranially then caudally. Of note, there is a delay in onset of anesthesia at the L5–S1 segments secondary to the larger size of these nerve roots.186 With thoracic injection, the LA spreads evenly from the site of injection, but meets resistance to blockade in the lumbar region because of the larger nerve roots. By controlling the dose in the thoracic region, a true segmental blockade affecting only the thoracic region can be established. Lumbar and sacral regions will be spared, thereby avoiding more extensive sympathetic blockade and subsequent associated hypotension and bladder dysfunction, as well as lower limb motor blockade.

Dose, Volume, and Concentration

The dose of LAs necessary for epidural anesthesia or analgesia is a function of the concentration of the solution and the volume injected. Concentration of the drug affects the density of the block; the higher the concentration, the more profound the motor and sensory block. Lower concentrations can selectively produce a sensory block.187

Volume and total LA dose are the variables that affect the degree of spread of the block. A larger volume of the same concentration of LA will block a greater number of segments. However, if the total dose of LA is unchanged but the concentration is doubled, the volume can be halved to achieve similar spread of LA.188 A generally accepted guideline for dosing epidural anesthesia in adults is 1–2 mL per segment to be blocked. This guideline should be adjusted for shorter patients and for very tall patients. For example, to achieve a T10 sensory level from an L3–L4 injection, approximately 8 mL of LA should be administered. Below concentrations of the equivalent of 1% lidocaine, motor block is minimal, regardless of the volume of the LA injected, unless doses are given at repeating intervals.

Time to repeat a dose of LAs depends on the duration of the drug. Doses should be administered before the block regresses to the point the patient experiences pain, commonly referred to as “time to two-segment regression.” This is defined as the time it takes for the sensory block to regress by two dermatome levels. When two-segment regression has occurred, one-third to one-half of the initial loading dose can safely be administered to maintain the block. For example, the time to two- segment regression of lidocaine is 60–140 minutes (Table 20).

TABLE 20. Redosing local anesthetics.


Concentration (%)

Time to Two-Segment Regression (min)

Recommended Time for “Top-Up” Dose From Initial Dose (min)

















Patient Positioning

Patient positioning during initiation of epidural blockade does not appear to affect the resultant spread of analgesia or anesthesia. The patient may be placed in either the lateral or sitting position. The midline of the spine is easier to palpate when the patient is sitting, especially in the obese patient, therefore making the block technically easier. Whether the patient is in the sitting or the lateral position, there is no significant difference in block height.189 It has been suggested in a study by Seow and associates that there is slightly faster onset time, duration, and density of motor block on the dependent side when the epidural is placed with the patient in the lateral position.190

Patient Characteristics: Age, Weight, Height, and Pregnancy

With advancing age, the LA dose required to attain a specific block is reduced. Some studies have observed a nonclinically significant difference in block height (between one and four segments higher) with a fixed volume and concentration of LA in patients older than age 50.191,192,193 Greater spread in the elderly may be related to the reduced size of the intervertebral foramina, which theoretically limits the egress of LAs from the epidural space. Decreased epidural fat, which allows more of the drug to bathe the nerves, and changes in the compliance of the epidural space, which may lead to enhanced cephalad spread, have also been proposed.194 There is little correlation between the spread of analgesia and the weight of the patient. However, in morbidly obese patients, there may be compression of the epidural space related to increased intra- abdominal pressure; a higher block may be attained with a given dose of LA.

Height appears to play little role in LA requirements. For short patients (≤5 ft 2 in.), the common practice has been to reduce the dose to 1 mL per segment to be blocked (instead of 2 mL per segment). Bromage suggested a more precise dosing regimen of increasing the dose of LA by 0.1 mL per segment for every 2 in. above 5 ft of height.195 The safest practice is to use incremental dosing and monitor the effect to avoid excessively high anesthetic levels.

Pregnancy causes an increased sensitivity to both LAs and general anesthetics, although the studies regarding the causes are conflicting. Elevated levels of progesterone and endogenous endorphins may contribute. Conflicting evidence regarding the spread of LA in pregnant versus nonpregnant individuals has been published.196,197

Intermittent Versus Continuous Epidural Block

The decision whether to use intermittent dosing after the initial loading dose, a continuous infusion, or patient-controlled or programmed intermittent bolus dosing may be influenced by the nature of the surgery or procedure, staffing, and equipment. All of these options can provide safe and effective epidural analgesia or anesthesia. Advantages of continuous infusion include greater cardiovascular stability, fewer labor requirements, decreased incidence of tachyphylaxis, decreased frequency and severity of side effects related to bolus injections, less rostral spread, decreased risk of the potential for contamination, and the ability to achieve a steady state of anesthesia. Intermittent manual bolus dosing, on the other hand, is simple and does not require additional equipment (eg, infusion devices).


Several factors influence the success of epidural blockade, including the clinician’s experience and knowledge of anatomy, patient preparation and positioning, the level of epidural catheter insertion, and the technique used to initiate the procedure. This section reviews factors that contribute to successful epidural placement, starting with patient selection and preparation, equipment requirements, and current recommendations for the prevention of infectious complications associated with neuraxial techniques. It then presents technical aspects of cervical, thoracic, and lumbar epidural placement and addresses various controversies related to the technique of neuraxial blockade, such as the optimal method to identify the epidural space and the efficacy of the epidural test dose.

Patient Evaluation


As in the case with any anesthetic, the risks and benefits of epidural placement should be discussed with the patient in a manner consistent with informed consent. Any concerns and questions should be addressed prior to the administration of premedication. When a language barrier exists, trained interpreters or telephone translation services should be utilized.

The patient’s medical history and active medication list should be reviewed prior to the initiation of epidural blockade, with particular emphasis on the presence of conditions that may predispose the patient to serious complications. Drug therapy that influences the patient’s clotting function or physiologic response to blockade of the sympathetic preganglionic fibers should be taken into consideration, including when the last dose was administered. The patient’s last oral intake should also be documented. For those patients receiving epidural blockade as the sole anesthetic or as an adjuvant to GA for elective surgical procedures, the ASA guidelines for nothing by mouth should be enforced. Patients with medical conditions that worsen with reduced afterload or preload (eg, severe AS, mitral stenosis, hypertrophic cardiomyopathy) and patients who may experience worsening shortness of breath, such as those with restrictive lung disease or severe COPD, may require additional testing. Clinical conditions that predispose patients to neuraxial infections, such as immunosuppression, DM, pancreatitis, and alcohol or drug abuse, may require further evaluation or laboratory studies. Pre-existing neurologic deficits or CNS disorders should be assessed and documented. History of sensitivity or adverse reaction to opioids or LAs and complications related to prior epidural procedures require further investigation. Physical examination should include an evaluation of the spine for evidence of scoliosis or prior back surgery, focal infection, severely limited range of motion, or other findings that may make epidural placement more challenging or impossible. Obesity, especially central obesity, may obscure surface landmarks.

Routine laboratory studies are not required for epidural placement in healthy patients for routine procedures. Many clinicians may choose to obtain a complete blood cell count (CBC), particularly when appreciable blood loss is expected or when the patient is known to be anemic. Baseline assessment of the patient’s coagulation status or platelet count should be obtained in patients with known or suspected coagulation dis- orders, bleeding diatheses, and thrombocytopenia, as well as in patients receiving antithrombotic or thrombolytic therapy or any medications known to affect platelet quality or function (besides routine NSAIDs).


  • Routine laboratory studies are not required for initiation of epidural blockade in healthy patients for routine procedures.
  • Patients with known or suspected bleeding disorders and those receiving antithrombotic or thrombolytic therapy require assessment of baseline coagulation status or platelet count (and possibly platelet function).
  • Patients undergoing surgeries with anticipated blood loss or hemodynamic changes may require additional workup, including a CBC.



A large-bore intravenous catheter for fluid or emergency drug administration must be secured prior to initiation of epidural blockade. Fluid preloading is not required and may be harmful in certain subsets of patients with decreased serum colloid oncotic pressure (eg, those with burns, preeclamptic patients).198 However, reversible conditions, such as severe hypovolemia, should be managed prior to block placement and dosing.

Appropriate monitoring during performance of epidural blockade depends on the purpose of the epidural block and when and where the epidural is to be dosed. Epidural blocks for analgesia, such as for labor analgesia, require intermittent blood pressure monitoring during placement and for the duration of the epidural infusion, as well as continuous pulse oximetry with heart rate monitoring during placement and block initiation. Electro- cardiogram (ECG) monitoring should be available. In laboring patients, fetal heart rate monitoring before and after placement is recommended if continuous monitoring is not feasible.

Sedatives or analgesics are not uncommonly administered to alleviate patient stress and discomfort during epidural placement and may require additional monitors and equipment, such as a nasal cannula. If premedications are administered, medical personnel who can provide continuous monitoring should be present. Of note, excessive sedation should be avoided to ensure patient cooperation during positioning, to detect the presence of paresthesias during placement, and to evaluate the level of sensory blockade and the effect of the test dose (if administered). Standard ASA monitors are required for initiation and intraoperative management of epidural anesthesia. Emergency drugs and equipment must be readily available during initiation of all central neuraxial procedures (Table 21).

Communication With Surgical Staff


A discussion with the surgical staff regarding the operative approach, the desired positioning of the patient, the estimated length of the surgical procedure, the anesthetic or analgesic goals of the blockade, and postoperative analgesic requirements can help to determine whether a continuous epidural, a single-shot epidural, or a CSE is preferable. The surgical staff can also share information about the patient that is not readily available in the chart or immediately apparent during the preoperative interview. When feasible, to minimize unnecessary delays the block can be initiated in the preoperative area or in the operating room while the nursing staff is setting up the surgical equipment. Wherever the block is performed, sufficient space for the anesthesiologist and, optimally, an assistant, as well as adequate lighting, monitoring, and resuscitation equipment are essential.

TABLE 21. Emergency equipment and drugs for initiation of neuraxial


Airway equipment

Ambu bag with mask Oxygen source

Oral and nasal airways Laryngoscope handles and blades Endotracheal tubes

Eschmann stylet/bougie Syringes and needles

Emergency drugs

Ephedrine Phenylephrine Epinephrine Atropine Sedative/hypnotic 20% lipid emulsion Succinylcholine



Commercially prepared, sterile, disposable epidural trays are available from several manufacturers. A standard kit typically includes the following: a sterile drape; prep swabs; 4 × 4 gauze sponges; a paper towel; povidone-iodine solution; an ampoule of 0.9% preservative-free sodium chloride; a 5- mL ampoule of 1.5% lidocaine with epinephrine 1:200,000; a 5-mL ampoule of 1% lidocaine for skin infiltration; a filtering device (needle or straw); a bacterial filter; needles and syringes of various sizes; a styletted epidural needle with cm markings; a 5- or 10-mL glass or plastic LOR syringe (either Luer lock or Luer slip); a catheter connector securing device; an epidural catheter with centimeter gradations and a connector/adapter; a thread assist device (TAD); a needle guard for sharps disposal; and labels.

In an adult epidural kit, the epidural needle is typically 17 or 18 gauge and 9 cm (roughly 3.5 in.) in length, with surface markings at 1-cm intervals. Longer needles up to 15 cm (6 in.) in length are available for obese patients. The Tuohy needle, which is commonly supplied in non-custom kits, has a curved tip with a blunt bevel designed to permit easier identification of tissue as the needle advances and facilitate passage of the epidural catheter. Wings at the junction of the needle shaft and hub may allow for better control as the needle is passed through tissue, particularly when using the “hanging drop” technique for epidural space identification, although some practitioners may prefer epidural needles without wings or with attachable wings (Figure 14). Epidural needles with a back-eye opening for exit of a spinal needle (for CSEs) and double-lumen needles with separate openings for the spinal needle and catheter are also available.

Epidural catheters vary in diameter, materials, and tip design. In commercially prepared kits, 19- gauge catheters are usually paired with 17-gauge epidural needles; 20-gauge catheters are paired with 18-gauge needles. Many currently available epidural catheters are nylon blends with varying degrees of stiffness to facilitate threading. Some stiff nylon catheters have specially designed flexible tips intended to veer away from veins, nerves, and other obstacles encountered in the epidural space. Wire-reinforced catheters embedded in either a polyurethane or nylon-blend catheter represent a more recent technological advance and are becoming increasingly popular (Figure 15). Adult versions are 19 gauge in diameter and designed for use with a 17-gauge epidural needle; pediatric versions are available from some manufacturers.

Many commercially available nylon and wire-reinforced catheters are manufactured in both single end-hole and multi-orifice versions (Figure 16). A lack of robust data precludes a full assessment of whether clinical outcomes, such as the incidence of paresthesias, epidural vein cannulation, intrathecal migration, and adequate analgesia, are improved with the uniport or multiport design. However, a 2009 prospective, single-blind, randomized controlled trial by Spiegel et al investigated the success of labor analgesia, the number of episodes of breakthrough pain requiring supplemental medicine, and the occurrence of complications, such as paresthesias and intravascular and intrathecal catheter placement, in 493 parturients who received either a single end-hole, wire-reinforced polyurethane catheter or a multiorifice, wire-reinforced nylon catheter.199 The authors found no statistically significant difference in outcomes between the two groups and postulated that the flexibility afforded by the wire coil may eliminate any of the potential advantages of the multiport design.


  • The use of wire-reinforced epidural catheters appears to reduce the incidence of complications associated with epidural techniques, including epidural vein cannulation, paresthesias, and inadequate analgesia.
  • Current data suggest that clinical outcomes are similar with the use of uniport and multiport spring-wound catheters; the flexibility afforded by the stainless steel coil appears to negate any potential benefits of a multiport design.

Additional equipment that may be needed for initiation of epidural procedures includes 0.5% chlorhexidine with ethanol (Hydrex®) or 2% chlorhexidine with 70% isopropyl alcohol (ChloraPrep®), which is not supplied in epidural trays; a transparent sterile, occlusive dressing for the puncture site; and tape to secure the catheter. To minimize the remote risk of chemical arachnoiditis, the skin disinfection solution should not make contact with the epidural drugs or equipment and should be given adequate time to dry. Usually a large clear dressing (eg, Tegaderm”) and adhesive tape are sufficient to prevent catheter dislodgement and to keep the epidural insertion site visible and clean. A sterile pen to label medications and a 25- or 27-gauge spinal needle (for CSEs) can be dropped onto the sterile field.


  • A clear sterile occlusive dressing is recommended to prevent catheter dislodgement.
  • The catheter and its centimeter markings should be vis- ible to the anesthesia provider to ensure that the catheter remains at the original insertion site and that CSF and heme return are absent prior to dosing.


FIGURE 14: Epidural needles: bevel and wing configuration.


FIGURE 15:Single end-hole wire-reinforced catheter.
(Used with permission from Epimed International.)


FIGURE 16: Multiorifice wire-reinforced catheter.
(Used with permission from Epimed International.)

Analgesia and Sedation During Block Initiation

Analgesia or sedation can be provided to improve patient comfort during neuraxial blockade. However, there is emerging evidence that intravenous sedatives may increase pain perception in an agent-type- and pain-type-specific manner.200 \ Light sedation with a benzodiazepine (most commonly midazolam) or a short-acting opioid prior to epidural placement is usually sufficient. This may also be appropriate for obstetric patients. In a small, double-blind randomized study, Frölich and col- leagues found that maternal analgesia and sedation with fentanyl and midazolam prior to spinal placement was not associated with adverse neonatal effects.201 Importantly, mothers in both the group that received premedication and the control group showed no difference in their ability to recall the births of their babies. For those who prefer to be “asleep” during epidural placement, a propofol infusion can be titrated to maintain sedation without respiratory impairment in selected clinical settings.

However, it is preferable to have adult patients awake and cooperative enough to alert the anesthesia provider to the presence of paresthesias during initiation of neuraxial blockade and to participate in assessment of the sensory level. In clinical scenarios in which the administration of premedication prior to epidural placement may not be appropriate, there appears to be a placebo effect from the use of gentler, more reassuring words during lidocaine skin wheal administration, which is often considered the most painful part of the procedure.202 Studies suggest that the following tips may also serve to reduce pain on injection of LA: Chloroprocaine (with or without sodium bicarbonate) may be less painful than lidocaine for skin infiltration203; adjusting the pH of lidocaine to approximate physiologic pH reduces pain on injection204; and cryoanalgesia (skin cooling) may be as effective as buffering the LA solution with sodium bicarbonate.205


The following tips may serve to reduce pain on injection of LA for skin infiltration:

  • Communication with the patient during the procedure and verbal reassurance
  • Adjusting the pH of lidocaine with the addition of sodium bicarbonate to more closely approximate physiologic pH
  • Skin cooling (cryoanalgesia) or topical anesthetic before skin puncture



1 Frölich MA, Caton D: Pioneers in epidural needle design. Anesth Analg 2001;93:215–220.

2 Cortés RC: Lumbar epidural anesthesia, 1931–1936: A second debut. Rev Esp Anestesiol Reanim 2005;52:159–168.

3 Dogliotti AM: Segmental peridural spinal anesthesia: A new method of block. Am J Surg 1933;20:107– 118.

4 Curbelo MM: Continuous peridural segmental anesthesia by means of a ureteral catheter. Curr Res Anesth Analg 1949;28:13–23.

5 Modig J, Borg T, Karlström G, et al: Thromboembolism after total hip replacement: Role of epidural and general anesthesia. Anesth Analg 1983;62:174–180.

6 Jørgensen LN, Rasmussen LS, Nielsen P, et al: Antithrombotic efficacy of continuous extradural analgesia after knee replacement. Br J Anaesth 1991;66:8–12.

7 Rodgers A, Walker N, Schug S, et al: Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: Results from overview of randomised trials. BMJ 2000;321:1–12.

8 Mauermann WJ, Shilling AM, Zuo Z: A comparison of neuraxial block versus general anesthesia for elective total hip replacement: A meta- analysis. Anesth Analg 2006;103:1018–1025.

9 Schindler I: Regional anesthesia in the elderly: Indications and contraindications. Acta Anaesthesiol Scand Suppl 1997;111:209–211.

10 Cherng CH, Wong CS, Chang FL, et al: Epidural morphine delays the onset of tourniquet pain during epidural lidocaine anesthesia. Anesth Analg 2002;94:1614–1616.

11 Christopherson R, Beattie C, Frank SM, et al: Perioperative morbidity in patients randomized to epidural

or general anesthesia for lower extremity vascular surgery. Anesthesiology 1993;79:422–434.

12 Sproviero M: Neuraxial anesthesia for adult genitourinary procedures. In Wong CA (ed): Spinal and Epidural Anesthesia. McGraw-Hill, 2007, pp 229–236.

13 Soriano D, Ajaj S, Chuong T, et al: Lidocaine spray and outpatient hysteroscopy: Randomized placebo-

controlled trial. Obstet Gynecol 2000;96:661–664.

14 Goldenberg M, Cohen SB, Etchin A, et al: A randomized prospective comparative study of general versus epidural anesthesia for transcervical hysteroscopic endometrial resection. Am J Obstet Gynecol 2001;184: 273–276.

15 Murphy M, Heit MH, Fouts L, et al. Effect of anesthesia on voiding function after tension-free vaginal

tape procedure. Obstet Gynecol 2003; 101:666–670.

16 Block BM, Liu SS, Rowlingson AJ, et al: Efficacy of postoperative epidural analgesia: A meta-analysis. JAMA 2003;290:2455–2463.

17 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.

18 Liu SS, Wu CL: Effect of postoperative analgesia on major postoperative complications: A systemic

update of the evidence. Anesth Analg 2007; 104:689–702.

19 Manion SC, Brennan TJ: Thoracic epidural analgesia and acute pain management. Anesthesiology 2011;115:181–188.

20 Nygård E, Kofoed KF, Freiburg J, et al: Effects of high thoracic epidural analgesia on myocardial blood

flow in patients with ischemic heart disease. Circulation 2005;111:2165–2170.

21 Scott NB, Turfrey DJ, Ray DA, 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: 528–535.

22 Loick HM, Schmidt C, Van Aken, 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;88:701–709.

23 Liu SS, Block BM, Wu CL: Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: A meta- analysis. Anesthesiology 2004;101:153–161.

24 Svircevic V, Nierich AP, Moons KG, et al: Thoracic epidural anesthesia for cardiac surgery: A


randomized trial. Anesthesiology 2011;114: 262–270.

25 Caputo M, Alwair H, Rogers CA, et al: Thoracic epidural anesthesia improves early outcomes in patients undergoing off-pump coronary artery bypass surgery: A prospective, randomized, controlled trial.

Anesthesiology 2011;114:380–390.

26 Møiniche 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;96:725–741.

27 Groeben H, Schäfer B, Pavlakovic G, et al: Lung function under high thoracic segmental epidural

anesthesia with ropivacaine or bupivacaine in patients with severe obstructive pulmonary disease undergoing breast surgery. Anesthesiology 2002;96:536–541.

28 Diaz N, Wong CA: Neuraxial anesthesia for general surgery. In Wong CA (ed): Spinal and Epidural Anesthesia. McGraw-Hill, 2007, pp 221–227.

29 Matot I, Scheinin O, Eid A, et al: Epidural anesthesia and analgesia in liver resection. Anesth Analg 2002;95:1179–1181.

30 Zhang HW, Chen YJ, Cao MH, et al: Laparoscopic cholecystectomy under epidural anesthesia: A

retrospective comparison of 100 patients. Am Surg 2012;78:107–110.

31 Asakura K, Nakazawa K, Tanaka N, et al. Case of cardiac arrest due to coronary spasm during laparoscopic distal gastrectomy. Masui 2011; 60:75–79.

32 Shir Y, Raja SN, Frank SM, et al: Intraoperative blood loss during radical retropubic prostatectomy.

Epidural versus general anesthesia. Urology 1995;45:993–999.

33 Gottschalk A, Smith DS, Jobes DR, et al: Preemptive epidural analgesia and recovery from radical prostatectomy: A randomized controlled trial. JAMA 1998;279:1076–1082.

34 Stevens RA, Mikat-Stevens M, Flanigan R, et al: Does the choice of anesthetic technique affect the recovery of bowel function after radical prostatectomy? Urology 1998;52:213–218.

35 Ozyuvaci E, Altan A, Karadeniz T, et al: General anesthesia versus epidural and general anesthesia in radical cystectomy. Urol Int 2005;74: 62–67.

36 Micali S, Jarrett TW, Pappa P, et al: Efficacy of epidural anesthesia for retroperitoneoscopic renal biopsy. Urology 2000;55:590.

37 Richards JT, Read JR, Chambers WA. Epidural anaesthesia as a method of pre-emptive analgesia for abdominal hysterectomy. Anaesthesia 1998;53:296–298.

38 Mihic DN, Abram SE: Optimal regional anaesthesia for abdominal hysterectomy: Combined subarachnoid and epidural block compared with other regional techniques. Eur J Anaesthesiol 1993;10: 297–301.

39 Holte K, Kehlet H: Epidural analgesia and risk of anastomotic leakage. Reg Anesth Pain Med 2001;26:111.

40 Kehlet H, Mogensen T: Hospital stay of 2 days after open sigmoidectomy with a multimodal rehabilitation programme. Br J Surg 1999;86: 227–230.

41 BardramL,Funch-JensenP,KehletH:Rapid rehabilitation in elderly patients after laparoscopic colonic resection. Br J Surg 2000;87: 1540–1545.

42 Blichfeldt-Lauridsen L, Hansen BD: Anesthesia and myasthenia gravis. Acta Anaesthesiol Scand 2012;56:17–22.

43 Kirsh JR, Diringer MN, Borel CO, et al: Preoperative lumbar epidural morphine improves postoperative analgesia and ventilatory function after transsternal thymectomy in patients with myasthenia gravis. Crit Care Med 1991;19:1474–1479.

44 Bagshaw O: A combination of total intravenous anesthesia and thoracic epidural for thymectomy in juvenile myasthenia gravis. Paediatr Anaesth 2007;17:370–374.

45 Hambly PR, Martin B: Anaesthesia for chronic spinal cord lesions. Anaesthesia 1998;53:273–289.
46 Lambert DH, Deane RS, Mazuzan JE: Anesthesia and the control of blood pressure in patients with spinal cord injury. Anesth Analg 1982;61: 344–348.

47 Ording H: Incidence of malignant hyperthermia in Denmark. Anesth Analg 1985;64:700–704.

48 van Lier F, van der Geest PJ, Hoeks SE, et al: Epidural analgesia is associated with improved health outcomes of surgical patients with chronic obstructive pulmonary disease. Anesthesiology 2011;115:315–



49 Mulroy MF, Salinas FV: Neuraxial techniques for ambulatory anesthesia. Int Anesthesiol Clin 2005;43:129–141.

50 Anghelescu DL, Faughnan LG, Baker JN, et al: Use of epidural and peripheral nerve blocks at the end of life in children and young adults with cancer: The collaboration between a pain service and a palliative care service. Paediatr Anaesth 2010;20:1070–1077.

51 Sielenkämper AW, Van Aken H: Epidural analgesia in sepsis: Too early to judge a new concept. Intensive Care Med 2004;30:1987–1989.

52 Strümper D, Louwen F, Durieux ME, et al: Epidural local anesthetics: A novel treatment for fetal growth retardation? Fetal Diagn Ther 2005; 20:208–213.

53 Hong JY, Lim KT: Effect of preemptive epidural analgesia on cytokine response and postoperative pain in laparoscopic radical hysterectomy for cervical cancer. Reg Anesth Pain Med 2008;33:44–51.

54 Exadaktylos AK, Buggy DJ, Moriarty DC, et al: Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology 2006;105:660–664.

55 Biki B, Mascha E, Moriarty DC, et al. Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: A retrospective analysis. Anesthesiology 2008;109:180–187.

56 Freise H, Van Aken H: Risks and benefits of thoracic epidural anaesthesia. Br J Anaesth 2011;107:859– 868.

57 Mutz C, Vagts DA: Thoracic epidural anesthesia in sepsis—is it harmful or protective? Crit Care 2009;13:182.

58 Su TM, Lan CM, Yang LC, et al: Brain tumor presenting with fatal herniation following delivery under epidural anesthesia. Anesthesiology 2002;96:508–509.

59 Grocott HP, Mutch WA: Epidural anesthesia and acutely increased intracranial pressure: Lumbar epidural space hydrodynamics in a porcine model. Anesthesiology 1996;85:1086–1091.

60 Leffert LR, Schwamm LH: Neuraxial anesthesia in parturients with intracranial pathology: A comprehensive review and reassessment of risk. Anesthesiology 2013;119:703–718.

61 Vandermeulen EP, Van Aken H, Vermylen J: Anticoagulants and spinal- epidural anesthesia. Anesth Analg 1994;79:1165–1177.

62 Horlocker TT, Wedel DJ, Rowlingson JC, et al: Regional anesthesia in the patient receiving

antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine evidence-based guidelines (third edition). Reg Anesth Pain Med 2010;35:64–101.

63 O’Rourke, N, Khan K, Hepner DL: Contraindications to neuraxial anesthesia. In Wong CA (ed): Spinal and Epidural Anesthesia. McGraw- Hill, 2007, pp 127–149.

64 Choi S, Brull R: Neuraxial techniques in obstetric and non-obstetric patients with common bleeding

diatheses. Anesth Analg 2009;109: 648–660.

65 Bader AM, Hunt CO, Datta S, et al: Anesthesia for the obstetric patient with multiple sclerosis. J Clin Anesth 1988;1:21–24.

66 Confavreux C, Hutchinson M, Hours MM, et al: Rate of pregnancy- related relapse in multiple sclerosis.

Pregnancy in Multiple Sclerosis Group. N Engl J Med 1998;339:285–291.

67 Hebl JR, Horlocker TT, Schroeder DR: Neuraxial anesthesia and analgesia in patients with preexisting central nervous system disorders. Anesth Analg 2006;103:223–228.

68 Lirk P, Birmingham B, Hogan Q: Regional anesthesia in patients with preexisting neuropathy. Int Anesthesiol Clin 2011;49:144–165.

69 Wiertlewski S, Magot A, Drapier S, et al: Worsening of neurologic symptoms after epidural anesthesia

for labor in a Guillain-Barré patient. Anesth Analg 2004;98:825–827.

70 Toledano RD, Pian-Smith MC: Human immunodeficiency virus: Maternal and fetal considerations and management. In Suresh MS, Segal BS, Preston RL, et al (eds): Shnider and Levinson’s Anesthesia for Obstetrics, 5th ed. Lippincott Williams & Wilkins, 2013, pp 595–605.

71 Crosby ET, Halpern SH, Rolbin SH: Epidural anaesthesia for caesarean section in patients with active

recurrent genital herpes simplex infections: A retrospective review. Can J Anaesth 1989;36:701–704.

72 Bader AM, Camann WR, Datta S: Anesthesia for cesarean delivery in patients with herpes simplex virus type-2 infections. Reg Anesth 1990; 15:261–263.


73 Brown NW, Parsons APR, Kam PCA: Anaesthetic considerations in a parturient with varicella presenting for caesarean section. Anaesthesia 2003;58:1092–1095.

74 Hebl JR, Horlocker TT, Kopp SL, et al: Neuraxial blockade in patients with preexisting spinal stenosis,

lumbar disk disease, or prior spine surgery: Efficacy and neurologic complications. Anesth Analg 2010;111: 1511–1519.

75 McDonald SB: Is neuraxial blockade contraindicated in the patient with aortic stenosis? Reg Anesth Pain Med 2004;29:496–502.

76 Ferguson EA, Paech MJ, Veltman MG: Hypertrophic cardiomyopathy and caesarean section: Intraoperative use of transthoracic echocardiography. Int J Obstet Anesth 2006;15:311–316.

77 Rosenquist RW, Birnbach DJ: Epidural insertion in anesthetized adults: Will your patients thank you?

Anesth Analg 2003;96:1545–1546.

78 Horlocker TT, Abel MD, Messick JM, et al: Small risk of serious neurologic complications related to lumbar epidural catheter placement in anesthetized patients. Anesth Analg 2003;96:1547–1552.

79 Han KR, Kim C, Park SK, et al: Distance to the adult cervical epidural space. Reg Anesth Pain Med


80 Stonelake PS, Burwell RG, Webb JK: Variation in vertebral levels of the vertebra prominens and sacral dimples in subjects with scoliosis. J Anat 1988;159:165–172.

81 Hughes RJ, Saifuddin A: Imaging of lumbosacral transitional vertebrae. Clin Radiol 2004;59:984–991.
82 Kim JT, Bahk JH, Sung J: Influence of age and sex on the position of the conus medullaris and Tuffier’s line in adults. Anesthesiology 2003;99: 1359–1363.

83 Saifuddin A, Burnett SJ, White J: The variation of position of the conus medullaris in an adult

population. A magnetic resonance imaging study. Spine 1998;23:1452–1456.

84 Vandermeersch E, Kick O, Mollmann M, et al: CSE—The combination of spinal and epidural anesthesia. Reg Anaesth 1991;14:108–112.

85 Lirk P, Hogan Q: Spinal and epidural anatomy. In Wong CA (ed): Spinal and Epidural Anesthesia. McGraw-Hill, 2007, 1–25.

86 Lee AJ, Ranasinghe JS, Chehade JM, et al: Ultrasound assessment of the vertebral level of the intercristal line in pregnancy. Anesth Analg 2011;113:559–564.

87 Van Gessel EF, Forster A, Gamulin Z: Continuous spinal anesthesia: Where do spinal catheters go?

Anesth Analg 1993;76:1004–1007.

88 Broadbent CR, Maxwell WB, Ferrie R, et al: Ability of anaesthetists to
identify a marked lumbar interspace. Anaesthesia 2000;55: 1122–1126.

89 Lirk P, Messner H, Deibl M, et al: Accuracy in estimating the correct intervertebral space level during lumbar, thoracic and cervical anaesthesia.
Acta Anaesthesiol Scand 2004;48:347–349.

90 Hogan QH: Lumbar epidural anatomy. A new look by cryomicrotome
section. Anesthesiology 1991;75:767–775.

91 Heylings DJ: Supraspinous and interspinous ligaments of the human
lumbar spine. J Anat 1978;125:127–131.

92 Han KR, Kim C, Park SK, et al: Distance to the adult cervical epidural
space. Reg Anesth Pain Med 2003;28:95–97.

93 Zarzur E: Anatomic studies of the human ligamentum flavum. Anesth
Analg 1984;63:499–502.
94 Williams DM, Gabrielsen TO, Latack JT, et al: Ossification in the
cephalic attachment of the ligamentum flavum. An anatomical and CT
study. Radiology 1984;150:423–426.

95 Brown DL: Spinal, epidural, and caudal anesthesia. In Miller RD,
Fleisher LE, Johns RA, et al (eds):

Miller’s Anesthesia, 6th ed. Elsevier,
2005, pp 1653–1683

96 Westbrook JL, Renowden SA, Carrie LE: Study of the anatomy of the
extradural region using magnetic resonance imaging. Br J Anaesth 1993;

97 Lirk P, Kolbitsch C, Putz G, et al: Cervical and high thoracic ligamentum
flavum frequently fails to fuse in the midline. Anesthesiology 2003;99:

98 Lirk P, Colvin J, Steger B, et al: Incidence of lower thoracic ligamentum
flavum midline gaps. Br J Anaesth 2005;94:852–855.


99 Lirk P, Moriggl B, Colvin J, et al: The incidence of lumbar ligamentum
flavum midline gaps. Anesth Analg 2004;98:1178–1180.

100 Reina MA, Villanueva MC, Machés F, et al: The ultrastructure of the human spinal nerve root cuff in the lumbar spine. Anesth Analg 2008;

101 Bernards CM: Sophistry in medicine: Lessons from the epidural space.
Reg Anesth Pain Med 2005;30:56–66.

102 Reina MA, De León Casasola O, Villanueva MC, et al: Ultrastructural
findings in human spinal pia mater in relation to subarachnoid
anesthesia. Anesth Analg 2004;98:1479–1485.

103 Blomberg RG: The lumbar subdural extraarchnoid space of humans: An
anatomical study using spinaloscopy in autopsy cases. Anesth Analg

104 Haines DE: On the question of a subdural space. Anat Rec 1991;230:

105 Boon JM, Abrahams PH, Meiring JH, et al: Lumbar puncture:
Anatomical review of a clinical skill. Clin Anat 2004;17:544–553.

106 Hogan QH: Epidural anatomy: New observations. Can J Anaesth

107 Bernards CM: Epidural anesthesia. In Mulroy MF, Bernards CM,
McDonald SB, et al (eds): A Practical Approach to Regional Anesthesia, 4th
ed. Lippincott Williams & Wilkins, 2009, p 104.

108 Igarashi T, Hirabayashi Y, Shimizu R, et al: The lumbar extradural
structure changes with increasing age. Br J Anaesth 1997;78:149–152.

109 Blomberg R: The dorsomedian connective tissue band in the lumbar epidural space of humans: An anatomical study using epiduroscopy in
autopsy cases. Anesth Analg 1986;65;747–752.

110 Hogan QH, Toth J: Anatomy of soft tissues of the spinal canal. Reg
Anesth Pain Med 1999;24;303–


111 Hogan QH: Distribution of solution in the epidural space: Examination
by cryomicrotome section. Reg Anesth Pain Med 2002;27:150–156.

112 Fujinaka MK, Lawson EF, Schukteis G, Wallace MS: Cervical epidural depth: correlation between

needle angle, cervical anatomy, and body
surface area. Pain Med 2012;13:665–669.

113 Aldrete JA, Mushin AU, Zapata JC, et al: Skin to cervical epidural space
distances as read from magnetic resonance imaging films: Consideration
of the “hump pad.” J Clin Anesth 1998;10:309–313.
114 Segal S, Beach M, Eappen S: A multivariate model to predict the distance from the skin to the epidural space in an obstetric population.
Reg Anesth 1996;21:451–455.

115 Sutton DN, Linter SP: Depth of extradural space and dural puncture.
Anaesthesia 1991;46:97–98.
116 Reynolds AF, Roberts PA, Pollay M, et al: Quantitative anatomy of the
thoracolumbar epidural space. Neurosurgery 1986;17:905–907.

117 Hogan QH: Epidural anatomy examined by cryomicrotome section. Influence of age, vertebral level, and disease. Reg Anesth 1996;21:

118 Toprak HI, Ozpolat Z, Ozturk E, et al: Hyperbaric bupivacaine affects
the doses of midazolam required for sedation after spinal anaesthesia. Eur J Anaesthesiol 2005;22:904–906.

119 Shono A, Sakura S, Saito Y, et al: Comparison of 1% and 2% lidocaine epidural anaesthesia combined with sevoflurane general anaesthesia utilizing a constant bispectral index. Br J Anaesth 2003;91:825–829. 120 Koo M, Sabaté A, Dalmau A, et al: Sevoflurane requirements during coloproctologic surgery: Difference between two different epidural regimens. J Clin Anesth 2003;15:97–102.

121 Eappen S, Kissin I: Effect of subarachnoid bupivacaine block on anesthetic requirements for thiopental

in rats. Anesthesiology 1998;88: 1036–1042.

122 Tverskoy M, Shagal M, Finger J, et al: Subarachnoid bupivacaine blockade decreases midazolam and thiopental hypnotic requirements. J Clin Anesth 1994;6:487–490.

123 Tverskoy M, Shifrin V, Finger J, et al: Effect of epidural bupivacaine block on midazolam hypnotic

requirements. Reg Anesth 1996;21: 209–213.

124 Hodgson PS, Liu SS, Gras TW: Does epidural anesthesia have general anesthetic effects? A prospective, randomized, double-blind, placebo- controlled trial. Anesthesiology 1999;91:1687–1692.


125 Reinoso-Barbero F, Martínez-García E, Hernández-Gancedo MC, et al: The effect of epidural bupivacaine on maintenance requirements of sevoflurane evaluated by bispectral index in children. Eur J Anaesthesiol 2006;23:460–464.

126 Holte K, Foss NB, Svensén C, et al: Epidural anesthesia, hypotension, and changes in intravascular volume. Anesthesiology 2004;100:281–286.

127 Meisner A, Rolf A, Van Aken H: Thoracic epidural anesthesia and the patient with heart disease:

Benefits, risks, and controversies. Anesth Analg 1997;85, 517–528.

128 Missant C, Claus P, Rex S, Wouters PF: Differential effects of lumbar and thoracic epidural anaesthesia on the haemodynamic response to acute right ventricular pressure overload. Br J Anaesth 2010;104:143– 149.

129 uggy DJ, Doherty WL, Hart EM, Pallet EJ: Postoperative wound oxygen tension with epidural or intravenous analgesia: A prospective, randomized, single-blind clinical trial. Anesthesiology 2002;97:952– 958.

130 Kabon B, Fleischmann E, Treschan T, et al: Thoracic epidural anesthesia increases tissue oxygenation

during major abdominal surgery. Anesth Analg 2003;97:1812–1817.

131 Olausson K, Magnusdottir H, Lurje L, et al: Anti-ischemic and anti- anginal effects of thoracic epidural anesthesia versus those of conventional medical therapy in the treatment of severe refractory unstable angina pectoris. Circulation 1997;96:2178–2182.

132 Richter A, Cederholm I, Fredrikson M, et al: Effect of long-term thoracic epidural analgesia on

refractory angina pectoris: A 10 year experience. J Cardiothorac Vasc Anesth 2012;26:822–828.

133 Rolf N, Van de Velde M, Wouters PF, et al: Thoracic epidural anesthesia improves functional recovery from myocardial stunning in conscious dogs. Anesth Analg 1996;83:935–940.

134 Rolf N, Meissner A, Van Aken H, et al: The effects of thoracic epidural anesthesia on functional

recovery from myocardial stunning in propofol anesthetized dogs. Anesth Analg 1997;84:723–729.
135 Freise H, Van Aken HK: Risks and benefits of thoracic epidural anaesthesia. Br J Anaesth 2011;107:859–868.

136 Svircevic V, van Dijk D, Nierich AP, et al: Meta-analysis of thoracic epidural anesthesia versus general anesthesia for cardiac surgery. Anesthesiology 2011;114:271–282.

137 Gu WJ, Wei CY, Huang DQ, et al: Meta-analysis of randomized controlled trials on the efficacy of thoracic epidural anesthesia in preventing atrial fibrillation after coronary artery bypass grafting. BMC Cardiovasc Disord 2012;12:1–7.

138 Freund FG, Bonica JJ, Ward RJ, et al: Ventilatory reserve and level of motor block during high spinal

and epidural anesthesia. Anesthesiology 1967;28:834–837.

139 Groeben H: Epidural anesthesia and pulmonary function. J Anesth 2006;20:290–299.

140 Lirk P, Hollmann MW: Outcome after regional anesthesia: Weighing risks and benefits. Minerva Anestesiol 2014;80:610–618.

141 Sielenkämper AW, Van Aken H: Thoracic epidural anesthesia: More than just anesthesia/analgesia. Anesthesiology 2003;99:523–525.

142 Brodner G, Van Aken H, Hertle L, et al: Multimodal perioperative management—combining thoracic

epidural analgesia, forced mobilization, and oral nutrition—reduces hormonal and metabolic stress and improves convalescence after major urologic surgery. Anesth Analg 2001;92:1594–1600.

143 Frank SM, Beattie C, Christopherson R, et al: Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia. Anesthesiology 1992;77: 252– 257.

144 Matsukawa T, Sessler DI, Christensen R, et al: Heat flow and distribution during epidural anesthesia.

Anesthesiology 1995;83: 961–967.

145 Szmuk P, Ezri T, Sessler D, et al: Spinal anesthesia speeds active postoperative rewarming. Anesthesiology 1997;87:1050–1054.

146 Backman SB: Regional anesthesia: sympathectomy-mediated vasodilation. Can J Anaesth 2009;56:702– 703.

147 Greene NM: Area of differential block in spinal anesthesia with hyperbaric tetracaine. Anesthesiology



148 Brull SJ, Greene NM: Zones of differential sensory block during extradural anaesthesia. Br J Anaesth 1991;66:651–655.

149 Valley MA, Bourke DL, Hamil MP, et al: Time course of sympathetic blockade during epidural anesthesia: Laser Doppler flowmetry studies or regional skin perfusion. Anesth Analg 1993;76:289–294.
150 Ginosar Y, Weiniger CF, Kurz V, et al: Sympathectomy mediated vasodilation: A randomized concentration ranging study of epidural bupivacaine. Can J Anaesth 2009;56:213–221.

151 Bengsston M: Changes in skin blood flow and temperature during spinal analgesia evaluated by laser Doppler flowmetry and infrared thermography. Acta Anaesthesiol Scand 1984;28:625–630.

152 Kimura T, Goda Y, Kemmotsu O, et al: Regional differences in skin blood flow and temperature during total spinal anaesthesia. Can J Anaesth 1992;39:123–127.

153 Bromage PR, Joyal AC, Binney JC: Local anesthetic drugs: penetration from the spinal extradural space into the neuraxis. Science 1963; 140: 392–394.

154 Moore D, Spierdijk J, VanKleef J, et al: Chloroprocaine neurotoxicity: Four additional cases. Anesth Analg 1982;61:155–159.

155 Lynch C 3rd: Depression of myocardial contractility in vitro by bupivacaine, etidocainem, and lidocaine. Anesth Analg 1986;65: 551–559.

156 Graf B, Martin E, Bosnjak Z: Stereospecific effect of bupivacaine isomers on atrioventricular conduction in the isolated perfused guinea pig heart. Anesthesiology 1997;86:410–419.

157 McClure JH: Ropivacaine. Br J Anaesth 1996;76:300–307.

158 Bader AM, Datta A, Flanagan H, et al: Comparison of bupivacaine- and ropivacaine-induced conduction blockade in isolated rabbit vagus nerve.
Anesth Analg 1989;68:724–727.

159 Curatolo M, Petersen-Felix S, Arendt-Nielsen L, et al: Adding sodium
bicarbonate to lidocaine enhances the depth of epidural blockade.
Anesth Analg 1998;86:341–347.

160 Corke BC, Carlson CG, Dettbarn WD: The influence of 2-chloroprocaine
on the subsequent analgesic potency of bupivacaine. Anesthesiology

161 Stanton-Hicks M, Berges PU, Bonica JJ: Circulatory effects of peridural
block. IV. Comparison of the effects of epinephrine and phenylephrine.
Anesthesiology 1973;39:308–314.

162 Bouguet D: Caudal clonidine added to local anesthetics enhances post-
operative analgesia after anal surgery in adults. Anesthesiology 1994;

163 Kroin JS, Buvanendran A, Beck DR, et al: Clonidine prolongation of
lidocaine analgesia after sciatic nerve block in rats is mediated via the hyperpolarization-activated cation current, not by alpha- adrenoreceptors. Anesthesiology 2004;101:488–494.

164 Landau R, Schiffer E, Morales M, et al: The dose-sparing effect of clonidine added to ropivacaine for labor epidural analgesia. Anesth Analg 2002;95:728–734.

165 Kayacan N, Arici G, Karsli B, et al: Patient-controlled epidural analgesia in labour: The addition of fentanyl or clonidine to bupivacaine. Agri 2004;16:59–66.

166 Novak-Jankovic V, Paver-Eržen V, Bovill JG, et al: Effect of epidural and intravenous clonidine on the neuro-endocrine and immune stress response in patients undergoing lung surgery. Eur J Anaesthesiol 2000; 17:50–56.

167 Matot I, Drenger B, Weissman C, et al: Epidural clonidine, bupivacaine and methadone as the sole analgesic agent after thoracotomy for lung resection. Anaesthesia 2004;59:861–866.

168 Wu CT, Jao SW, Borel CO: The effect of epidural clonidine on perioperative cytokine response, postoperative pain, and bowel function in patients undergoing colorectal surgery. Anesth Analg 2004;99: 502–509.

169 Roelants F, Lavand’homme PM, Mercier-Fuzier V: Epidural administration of neostigmine and clonidine to induce labor analgesia: Evaluation of efficacy and local anesthetic-sparing effect.

Anesthesiology 2005;102:1205–1210.

170 Boogmans T, Vertommen J, Valkenborgh T, et al: Epidural neostigmine and clonidine improves the quality of combined spinal epidural analgesia in labour: A randomised, double-blind controlled trial. Eur J Anaesthesiol 2014;31:190–196.


171 Roelants F, Lavand’homme PM: Epidural neostigmine combined with sufentanil provides balanced and selective analgesia in early labor. Anesthesiology 2004;101:439–444.

172 Omais M, Lauretti G, Paccola CA: Epidural morphine and neostigmine for postoperative analgesia after orthopedic surgery. Anesth Analg 2002;95:1698–1701.

173 Habib AS, Gan TJ. Use of neostigmine in the management of acute postoperative pain and labour pain: A review. CNS Drugs 2006;20: 821–839.

174 Lauretti GR, Gomes JM, Reis MP, Pereira NL:. Low doses of epidural ketamine or neostigmine, but not

midazolam, improve morphine analgesia in epidural terminal cancer pain therapy. J Clin Anesth 1999; 11(8):663–668.

175 Lauretti GR, de Oliveira R, Perez MV, et al: Postoperative analgesia by intraarticular and epidural neostigmine following knee surgery. J Clin Anesth 2000;12:444–448.

176 Johansen MJ, Gradert TL, Sattefield WC, et al: Safety of continuous intrathecal midazolam infusion in the sheep model. Anesth Analg 2004;98:1528–1535.

177 Bharti N, Madan R, Mohanty PR, et al: Intrathecal midazolam added to bupivacaine improves the

duration and quality of spinal anaesthesia. Acta Anaesthesiol Scand 2003;47:1101–1105.

178 Tucker AP, Mezzatesta J, Nadeson R, et al: Intrathecal midazolam II: Combination with intrathecal fentanyl for labor pain. Anesth Analg 2004;98:1521–1527.

179 Ugur B, Basaloglu K, Yurtseven T, et al: Neurotoxicity with single dose intrathecal midazolam

administration. Eur J Anaesthesiol 2005;22: 907–912.

180 Yaksh TL, Allen JW: Preclinical insights into the implementation of intrathecal midazolam: a cautionary tale. Anesth Analg 2004;98: 1509–1511.

181 Gambling D, Hughes T, Martin G, et al: A comparison of Depodur, a novel, single-dose extended- release epidural morphine, with standard epidural morphine for pain relief after lower abdominal surgery. Anesth Analg 2005;100:1065–1074.

182 Viscusi ER, Martin G, Hartrick CT, et al: Forty-eight hours of postoperative pain relief after total hip

arthroplasty with a novel, extended-release epidural morphine formulation. Anesthesiology 2005;102:1014–1022.

183 Carvalho B, Riley E, Cohen SE, et al: Single-dose, sustained release epidural morphine in the management of postoperative pain after elective cesarean delivery: Results of a multicenter randomized controlled study. Anesth Analg 2005;100:1150–1158.

184 Magnusdottir H, Kimo K, Ricksten S: High thoracic epidural analgesia does not inhibit sympathetic

nerve activity in the lower extremities. Anesthesiology 1999;91:1299–1304.

185 Basse L, Werner M, Kehlet H: Is urinary drainage necessary during continuous epidural anesthesia after colonic resection. Reg Anesth Pain Med 2000;25:498–501.

186 Galindo A, Hernandez J, Benavides O, et al: Quality of spinal extradural anesthesia: The influence of

spinal nerve root diameter. Br J Anaesth 1975;47:41–47.

187 uggan J, Bowler GM, McClure JH, et al: Extradural block with bupivacaine: Influence of dose, volume, concentration and patient characteristics. Br J Anaesth 1998;61:324–331.

188 Sakura S, Sumi M, Kushizaki H, et al: Concentration of lidocaine affects intensity of sensory block

during lumbar epidural anesthesia. Anesth Analg 1999;88:123–127.

189 Hodgkinson R, Husain FJ: Obesity, gravity, and spread of epidural anesthesia. Anesth Analg 1981;60:421–424.

190 Seow LT, Lips FJ, Cousins MJ: Effect of lateral position on epidural blockade for surgery. Anaesth

Intensive Care 1983;11:97–102.

191 Park WY, Hagins FM, Rivat EL, et al: Age and epidural dose response in adult men. Anesthesiology 1982;56:318–320.

192 Park WY, Massengale M, Kim SI, et al: Age and spread of local anesthetic solutions in the epidural

space. Anesth Analg 1980;59:768–771.

193 Veering BT, Burm AG, van Kleef JW, et al: Epidural anesthesia with bupivacaine: Effects of age on neural blockade and pharmacokinetics. Anesth Analg 1987;66:589–593.

194 Hirabayashi Y, Shimizu R, Matsuda I, et al: Effect of extradural compliance and resistance on spread of


extradural analgesia. Br J Anaesth 1990;65:508–513.

195 Bromage PR, Bufoot MF, Crowell DE, et al: Quality of epidural blockade. I. Influence of physical factors. Br J Anaesth 1964;36: 342–352.

196 Grundy EM, Zamora AM, Winnie AP: Comparison of spread of epidural anesthesia in pregnant and

nonpregnant women. Anesth Analg 1978;57:544–546.

197 Arakawa M: Does pregnancy increase the efficacy of lumbar epidural anesthesia? Int J Obstet Anesth 2004;13:86–90.

198 Henke VG, Bateman BT, Leffert LR: Spinal anesthesia in severe preeclampsia. Anaesth Analg


199 Spiegel JE, Vasudevan A, Li Y, et al: A randomized prospective study
comparing two flexible epidural catheters for labour analgesia. Br J
Anaesth 2009;103:400–405.

200 Frölich MA, Zhang K, Ness TJ: Effect of sedation on pain perception.
Anesthesiology 2013;118:611– 621.

201 Frölich MA, Burchfield DJ, Euliano TY, et al: A single dose of fentanyl
and midazolam prior to Cesarean section have no adverse neonatal
effects. Can J Anaesth 2006;53:79–85.

202 Varelmann D, Pancaro C, Cappiello EC, et al: Nocebo-induced
hyperalgesia during local anesthetic injection. Anesth Analg 2010;110:

203 Marica LS, O’Day T, Janosky J, et al: Chloroprocaine is less painful than
lidocaine for skin infiltration anesthesia. Anesth Analg 2002;94:

204 Cepeda MS, Tzortzopoulou A, Thackrey M, et al: Adjusting the pH of
lidocaine for reducing pain on injection. Cochrane Database Syst Rev

205 Al Shahwan MA: Prospective comparison between buffered 1%
lidocaine-epinephrine and skin cooling in reducing the pain of local
anesthetic infiltration. Dermatol Surg 2012;38:1654–1659.

206 Hamilton CL, Riley ET, Cohen SE: Changes in the position of epidural catheters associated with patient movement. Anesthesiology 1997;86:

207 Richardson MG, Thakur R, Abramowicz JS, et al: Maternal posture
influences the extent of sensory block produced by intrathecal dextrose- free bupivacaine with fentanyl for labor analgesia. Anesth Analg 1996;83:1229–1233.

208 Tsen LC: Neuraxial techniques for labor analgesia should be placed in the lateral position. Int J Obstet Anesth 2008;17:146–149.

209 American Society of Anesthesiologists Task Force on Infectious Complications Associated With Neuraxial Techniques: Practice advisory for the prevention, diagnosis, and management of infectious complications associated with neuraxial techniques. Anesthesiology 2010;112:530–545.

210 Malhotra S, Dharmadasa A, Yentis SM: One vs two applications of chlorhexidine/ethanol for disinfecting the skin: Implications for regional anaesthesia. Anaesthesia 2011;66:574–578.

211 Bogod DS: The sting in the tail: Antisepsis and the neuraxis revisited. Anaesthesia 2012;67:1305–1309. 212 Segal S, Arendt KW: A retrospective effectiveness study of loss of resistance to air or saline for identification of the epidural space. Anesth Analg 2010;110:558–563.

213 Laviola S, Kirvelä M, Spoto M: Pneumocephalus with intense headache and unilateral pupillary dilatation after accidental dural puncture during epidural anesthesia for cesarean section. Anesth Analg 1999;88: 582–583.

214 Van de Velde M: Identification of the epidural space: Stop using the loss of resistance to air technique! Acta Anaesthiol Belg 2006;57: 51–54.

215 Dalens B, Bazin JE, Haberer JP: Epidural bubbles as a cause of incomplete analgesia during epidural anesthesia. Anesth Analg 1987;66: 679–683.

216 Naulty JS, Ostheimer GW, Datta S, et al: Incidence of venous air embolism during epidural catheter insertion. Anesthesiology 1982;57: 410–412.

217 Evron S, Sessler D, Sadan O, et al: Identification of the epidural space: Loss of resistance with air, lidocaine, or the combination of air and lidocaine. Anesth Analg 2004;99:245–250.

218 Balki M, Lee Y, Halpern S, et al: Ultrasound imaging of the lumbar spine in the transverse plane: The correlation between estimated and actual depth to the epidural space in obese parturients. Anesth Analg


2009;108: 1876–1881.

219 Mhyre JM: Why do pharmacologic test doses fail to identify the unintended intrathecal catheter in obstetrics? Anesth Analg 2013; 116:4–7.

220 Tsui B, Gupta S, Finucane B: Confirmation of epidural catheter placement using nerve stimulation. Can J Anaesth 1998;45: 640–644,1998.

221 Lyons GR, Kocarev MG, Wilson RC, et al: A comparison of minimum local anesthetic volumes and doses of epidural bupivacaine (0.125% w/v and 0.25% w/v) for analgesia in labor. Anesth Analg 2007;104: 412–415.

222 Wong CA, Ratliff JT, Sullivan JT, et al: A randomized comparison of programmed intermittent epidural bolus with continuous epidural infusion for labor analgesia. Anesth Analg 2006;102:904–909.

223 Heesen M, Klohr S, Rossaint R, et al: Can the incidence of accidental dural puncture in laboring women be reduced? A systematic review and meta-analysis. Minerva Anestesiol 2013;79:1187–1197.

224 Van de Velde M, Schepers R, Berends N, et al: Ten years of experience with accidental dural puncture and post-dural puncture headache in a tertiary obstetric anaesthesia department. Int J Obstet Anesth 2008;17: 329–335.

225 Agerson AN, Scavone BM: Prophylactic epidural blood patch after unintentional dural puncture for the

prevention of postdural puncture headache in parturients. Anesth Analg 2012;115:133–136.

226 Bauer ME, Kountanis JA, Tsen LC, et al: Risk factors for failed conversion of labor epidural analgesia to cesarean delivery anesthesia: A systematic review and meta-analysis of observational trials. Int J Obstet Anesth 2012;21:294–309.

227 Toledano RD, Kodali BS, Camann WR: Anesthesia drugs in the obstetric and gynecologic practice. Rev

Obstet Gynecol 2009;2: 93–100.

228 Mhyre JM, Greenfield ML, Tsen LC, et al: A systematic review of randomized controlled trials that evaluate strategies to avoid epidural vein cannulation during obstetric epidural catheter placement. Anesth Analg 2009;108:1232–1242.

229 Neal JM, Mulroy MF, Weinberg GL: American Society of Regional Anesthesia and Pain Medicine

checklist for managing local anesthetic systemic toxicity: 2012 version. Reg Anesth Pain Med 2012;37:16– 18.

230 Bhole MV, Manson AL, Seneviratne SL, et al: IgE-mediated allergy to local anaesthetics: Separating fact from perception: A UK perspective. Br J Anaesth 2012;108:903–911.

231 Rice I, Wee MY, Thomson K: Obstetric epidurals and chronic adhesive arachnoiditis. Br J Anaesth


232 Taniguchi M, Bollen AW, Drasner K: Sodium bisulfite: Scapegoat for chloroprocaine neurotoxicity? Anesthesiology 2004;100:85–91.

233 Checketts MR: Wash & go—but with what? Skin antiseptic solutions for central neuraxial block.

Anaesthesia 2012;67:819–822.

234 Na EH, Han SJ, Kim MH: Delayed occurrence of spinal arachnoiditis following a caudal block. J Spinal Cord Med 2011;34:616–619.

235 Ross JS, Masaryk T, Modic M, et al: MR imaging of lumbar arachnoiditis. Am J Roentgenol 1987;149:1025–1032.

236 Wang YL, Hsieh JR, Chung HS, et al: The local addition of tenoxicam reduces the incidence of low

back pain after lumbar epidural anesthesia. Anesthesiology 1998;89:1414–1417.

237 Stevens RA, Urmey WF, Urquhart, et al: Back pain after epidural anesthesia with chloroprocaine. Anesthesiology 1993;78:492–497.

238 Hakim SH, Narouze S, Shaker NN, et al: Risk factors for new-onset persistent low-back pain following nonobstetric surgery performed with epidural anesthesia. Reg Anesth Pain Med 2012;37:175–182.

239 Wilkinson HA: Field block anesthesia for lumbar puncture. JAMA 1983;249:2177.

240 Wang YL, Tan PP, Yang CH, et al: Epidural dexamethasone reduces the incidence of backache after lumbar epidural anesthesia. Anesth Analg 1997;84:376–378.

241 Breen TW: Epidural analgesia and back pain. In Halpern Sh, Douglas MJ (eds): Evidence-Based Obstetric Anesthesia. BMJ Books, 2005, pp 208–216.

242 Arendt K, Demaerschalk BM, Wingerchuck DM, et al: Atraumatic lumbar puncture needles: After all


these years, are we still missing the point? Neurologist 2009;15:17–20.

243 Brownridge P: The management of headache following accidental dural puncture in obstetric patients. Anaesth Intensive Care 1983;11:4–15.

244 Headache Classification Committee of the International Headache Society: The international

classification of headache disorders, third edition. Cephalalgia 2013;33:629–808.

245 Webb CA, Weyker PD, Zhang L, et al: Unintentional dural puncture with a Tuohy needle increases risk of chronic headache. Anesth Analg 2012;115:124–132.

246 Apfel CC, Saxena A, Cakmakkaya OS, et al: Prevention of postdural puncture headache after accidental dural puncture: A quantitative systematic review. Br J Anaesth 2010;105:255–263.

247 Oedit R, van Kooten F, Bakker SL, et al: Efficacy of the epidural blood patch for the treatment of post

lumbar puncture headache BLOPP: A randomised, observer-blind, controlled clinical trial. BMC Neurol 2005; 5:12.

248 van Kooten F, Oedit R, Bakker SL, et al: Epidural blood patch in post dural puncture heachache: A randomized, observed-blind, controlled clinical trial. J Neurol Neurosurg Psychiatry 2008;79:553–559.
249 Angle P, Tang SL, Thompson D, et al: Expectant management of postdural puncture headache increases hospital length of stay and emergency room visits. Can J Anaesth 2005;52:397–402.

250 Paech MJ, Doherty DA, Christmas T, et al: The volume of blood for epidural blood patch in obstetrics:

A randomized, blinded clinical trial. Anesth Analg 2011;113:126–133.

251 Haines DE: On the question of a subdural space. Anat Rec 1991; 230:3–21.

252 Lubenow T, Keh-Wong E, Kristof K, et al: Inadvertent subdural injection: A complication of epidural block. Anesth Analg 1988;67: 175–179.

253 Paech MJ, Godkin R, Webster S: Complications of obstetric epidural analgesia and anaesthesia: A prospective analysis of 10,995 cases. Int J Obstet Anesth 1998;7:5–11.

254 Cappiello E, Tsen LC: Complications and side effects of central neuraxial techniques. In Wong CA (ed):

Spinal and Epidural Anesthesia. McGraw- Hill, 2007, pp 152–182.

255 Grewal S, Hocking G, Wildsmith JA: Epidural abscesses. Br J Anaesth 2006;96:292–302.

256 Darouiche R, Spinal epidural abscess: N Engl J Med 2006;355: 2012–2020.

257 Connor DE, Chittiboina P, Caldito G, et al: Comparison of operative and nonoperative management of spinal epidural abscess: A retrospective review of clinical and laboratory predictors of neurologic outcome. J Neurosurg Spine 2013;19:119–127.

258 Curry WT, Hoh BL, Amin-Hanjani S, et al: Spinal epidural abscess: Clinical presentation, management, and outcome. Surg Neurol 2005;63:364–371.

259 Okano K, Kondo H, Tsuchiya R, et al: Spinal epidural abscess associated with epidural catheterization: Report of a case and a review of the literature. Jpn J Clin Oncol 1999;29:49–52.

260 Danner RL, Hartman BJ: Update on spinal epidural abscess: 35 cases and review of the literature. Rev Infect Dis 1987;9:265–274.

261 Huang PY, Chen SF, Chang WN, et al: Spinal epidural abscess in adults caused by Staphylococcus aureus: Clinical characteristics and prognostic factors. Clin Neurol Neurosurg 2012;114:572–576.
262 Baer ET: Post-dural puncture bacterial meningitis. Anesthesiology 2006; 105:381–393.

263 Reynolds F: Neurological infections after neuraxial anesthesia. Anesthesiol Clin 2008;26:23–52.

264 Usubiaga JE: Neurological complications following epidural anesthesia. Int Anaesthesiol 1975;13:1–


265 Kane RE: Neurologic deficits following epidural or spinal anesthesia. Anesth Analg 1981;60:150–161.
266 Kao M, Tsai S, Tsou M, et al: Paraplegia after delayed detection of inadvertent spinal cord injury during thoracic epidural catheterization in an anesthetized elderly patient. Anesth Analg 2004;99:580–583.

267 Loo CC, Irestedt L: Cauda equina syndrome after spinal anaesthesia with hyperbaric 5% lignocaine: A review of six cases of cauda equina syndrome reported to the Swedish Pharmaceutical Insurance 1993– 1997. Acta Anaesthesiol Scand 1999;43:371–379.

268 Lambert DH, Hurley RJ: Cauda equina syndrome and continuous spinal anesthesia. Anesth Analg 1991;72:817–819.

269 Gerancher JC: Cauda equina syndrome following a single spinal administration of 5% hyperbaric lidocaine through a 25-gauge Whitacre needle. Anesthesiology 1997;87:687–689.


270 Benson JS: US Food and Drug Administration safety alert: Cauda equine syndrome associated with the use of small-bore catheters in continuous spinal anesthesia. AANA J 1992;60:223.

271 Rigler ML, Drasner K, Krejcie, TC, et al: Cauda equina syndrome after continuous spinal anesthesia.

Anesth Analg 1991;72:275–281.

272 Gaiser RR: Should intrathecal lidocaine be used in the 21st century? J Clin Anesth 2000;12:476–481. 273 Walters MA, Van de Velde M, Wilms G: Acute intrathecal haematoma following neuraxial anaesthesia: Diagnostic delay after apparently normal radiological imaging. Int J Obstet Anesth 2012;21:181–185.

274 Auroy Y, Narchi P, Messiah A, et al: Serious complications related to regional anesthesia: Results of a prospective survey in France. Anesthesiology 1997;87:479–486.

275 Pollard JB: Common mechanisms and strategies for prevention and treatment of cardiac arrest during

epidural anesthesia. J Clin Anesth 2002;14:52–56.

276 Pollard JB: Cardiac arrest during spinal anesthesia: Common mechanisms and strategies for prevention. Anesth Analg 2001;92:252–256.

277 Pollard JB: Cardiac arrest during spinal anesthesia: Common mechanisms and strategies for prevention.

Anesth Analg 2001;92:252–256.

278 Curatolo M, Scaramozzino P, Venuti FS, et al: Factors associated with hypotension and bradycardia after epidural blockade. Anesth Analg 1996;83:1033–1040.

279 Liguori GA, Sharrock NE: Asystole and severe bradycardia during epidural anesthesia in orthopedic patients. Anesthesiology 1997;86: 250–257.

280 Camann WR, Hortvet LA, Hughes N, et al: Maternal temperature regulation during extradural analgesia for labour. Br J Anaesth 1991;67: 565–568.

281 Borgeat A, Ekatodramis G, Schenker CA: Postoperative nausea and vomiting in regional anesthesia: A

review. Anesthesiology 2003;98: 530–547.

282 Allen TK, Jones CA, Habib AS: Dexamethasone for the prophylaxis of postoperative nausea and vomiting associated with neuraxial morphine administration: A systematic review and meta-analysis. Anesth Analg 2012;114:813–822.