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Part 2 book “Hadzic’s textbook of regional anesthesia and acute pain management” has contents: Epidural anesthesia, caudal anesthesia, combined spinal and epidural anesthesia, postdural puncture headache, ultrasound-guided head and neck nerve blocks,… and other contents.
380 SECTION Epidural Anesthesia CHAPTER 24 Epidural Anesthesia and Analgesia Roulhac D Toledano and Marc Van de Velde* INTRODUCTION 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-tosevere 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 reviews (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 * The authors would like to thank Michael A Maloney, MB, BAO, ChB, for his help with the tables and figures Hadzic_Ch24_p380-445.indd 380 anatomy, the traditional epinephrine test dose, methods used to identify the epidural space, and whether particular clinical outcomes may be improved with epidural techniques when compared 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 elsewhere 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.1 Nineteen 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.2 Within 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.3 Contemporaneously, the Argentine surgeon Alberto Gutiérrez described the “sign of the drop” for identification of the epidural space 23/02/17 4:32 PM Epidural Anesthesia and Analgesia INDICATIONS 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 24–1) 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 ■■ 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 Hadzic_Ch24_p380-445.indd 381 TABLE 24–1. Examples of applications for epidural blockade Specialty Orthopedic surgery Surgical Procedure 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 CHAPTER CHAPTER 24 X 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 availability 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 381 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 24–2) 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 23/02/17 4:32 PM 382 CLINICAL PRACTICE OF REGIONAL ANESTHESIA TABLE 24–2. Orthopedic surgeries suitable for epidural, combined spinal-epidural, or integrated epidural–general anesthesia PART Procedure Closed reduction and external fixation of pelvis Sensory Level Required Neuraxial technique seldom adequate for surgery; epidural useful for postoperative analgesia Hip arthroplasty, arthrodesis, synovectomy T10 Open reduction internal fixation of acetabular fracture T10 Open reduction internal fixation of femur, tibia, ankle, or foot T12 Closed reduction and external fixation of femur and tibia T12 Above- and below-knee amputation T12 (T8 with tourniquet) Knee arthrotomy T12 (T8 with tourniquet) Arthroscopy of knee T12 Repair/reconstruction of knee ligaments T12 Total knee replacement T12 (T8 with tourniquet) Distal tibia, ankle, and foot procedures T12 Ankle arthroscopy, arthrotomy, arthrodesis T12 Transmetatarsal amputation T12 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 intraoperative hypotension is kept to a minimum.9 However, Hadzic_Ch24_p380-445.indd 382 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 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 23/02/17 4:32 PM Epidural Anesthesia and Analgesia TABLE 24–3. Examples of vascular procedures performed with epidural blockade Aortofemoral bypass Renal artery bypass Mesenteric artery bypass Infrainguinal arterial bypass with saphenous vein or synthetic graft Embolectomy Early detection of mental status changes Early detection of breakthrough pain (indicative of capsular/bladder perforation) Reduced blood loss CHAPTER CHAPTER 24 X Abdominal aortic aneurysm repair (neuraxial technique seldom adequate as sole anesthetic) TABLE 24–4. Benefits of central neuraxial blockade versus general anesthesia for transurethral resection of the prostate 383 Decreased incidence of deep vein thrombosis Decreased incidence of circulatory overload Improved postoperative pain control Thrombectomy Endovascular procedures (intraluminal balloon dilation with stent placement; aneurysm repair) (Table 24–3) 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 compared with GA for these procedures,11 although epidural techniques may be superior for promoting graft survival 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 24–4).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) 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 patients Hadzic_Ch24_p380-445.indd 383 because of the risk of autonomic hyperreflexia (AH) (see separate 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 24–5) 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 24–6) A dilation and curettage (D&C) can be performed under paracervical block, GA, or TABLE 24–5. Sensory level required for genitourinary procedures Procedure Nephrectomy Sensory Level Required Consider combined general-epidural anesthesia Cystectomy T4 Extracorporeal shock wave lithotripsy T6 Open prostatectomy T8 Ureteral stone extraction T8 Cystoscopy T9 Transurethral resection of prostate T9 Surgery involving testes T10 Surgery involving penis L1 Urethral procedures Sacral block 23/02/17 4:32 PM 384 CLINICAL PRACTICE OF REGIONAL ANESTHESIA TABLE 24–6. Vaginal gynecologic procedures suitable for epidural blockade Dilation and curettage PART Hysteroscopy (with or without distention media) Urinary incontinence procedures Hysterectomy 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.15 A 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 ■■ Thoracic Epidural Anesthesia and Analgesia The benefits of and indications for thoracic epidural anesthesia (TEA) are expanding (Table 24–7) TEA offers superior perioperative 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 24–1) It also reviews the expanding role of TEA for video-assisted thoracic surgery (VATS) and laparoscopic surgery TABLE 24–7. 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 Hadzic_Ch24_p380-445.indd 384 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.24 The 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 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 23/02/17 4:32 PM Epidural Anesthesia and Analgesia 385 CHAPTER CHAPTER 24 X Cervical Thoracic Lumbar Thoracic surgery - Thoracotomy - Pectus repair - Thoracic aortic aneurysm repair Upper abdominal surgery - Esophagectomy - Gastrectomy - Pancreatectomy - Hepatic resection Lower abdominal surgery - Abdominal aortic aneurysm repair - Colectomy - Abdominal perineal resection Sacral Hadzic - Lanceeaa// NYS Ha YSO OR RA FIGURE 24–1. Level of placement in surgeries performed with thoracic epidural anesthesia and analgesia (Table 24–8) 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 Hadzic_Ch24_p380-445.indd 385 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 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 23/02/17 4:32 PM 386 CLINICAL PRACTICE OF REGIONAL ANESTHESIA TABLE 24–8. Indications for thoracic epidural anesthesia and analgesia PART Anatomic Region Thorax Procedure 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 Suprainguinal Vascular Procedures with moderate-to-severe comorbidities.27 The 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 24–9).28 The epidural catheter can be introduced at T2–T4 to achieve segmental TABLE 24–9. Sensory level required for breast procedures Surgery Modified radical mastectomy Segmental Blockade C5–T7 Mastectomy with transverse rectus abdominus flap C5–L1 Partial mastectomy; breast augmentation T1–T7 Hadzic_Ch24_p380-445.indd 386 blockade of the thoracic dermatomes for most breast procedures; placement at T8–T10 is appropriate for TRAM flap reconstruction 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,29 and 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 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 23/02/17 4:32 PM Epidural Anesthesia and Analgesia 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, Hadzic_Ch24_p380-445.indd 387 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 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) CHAPTER CHAPTER 24 X 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.36 387 ■■ 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 23/02/17 4:32 PM 388 CLINICAL PRACTICE OF REGIONAL ANESTHESIA PART 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.47 Both 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 Hadzic_Ch24_p380-445.indd 388 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 Miscellaneous 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 23/02/17 4:32 PM Epidural Anesthesia and Analgesia TABLE 24–10. Contraindications to epidural blockade Absolute Patient refusal Severe coagulation abnormalities (eg, frank disseminated intravascular coagulation) Relative and controversial Sepsis 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 CHAPTER CHAPTER 24 X 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 prostate55 cancer These protective effects may reflect both the decreased opioid requirements and the reduced neurohumoral stress response associated with epidural blockade.56 389 CONTRAINDICATIONS 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 24–10) 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 Hadzic_Ch24_p380-445.indd 389 ■■ 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 concurrent antibiotic, intravenous fluid, and vasopressor administration may be feasible Increased Intracranial Pressure Accidental dural puncture (ADP) in the setting of elevated intracranial 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 23/02/17 4:32 PM 848 CHAPTER 45 Acute and Chronic Pain Management in Children Rishi M Diwan ACUTE PAIN MANAGEMENT INTRODUCTION The treatment and alleviation of pain constitute a basic human right that exists regardless of age.1,2 Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage.3 Previous experience and management of pain, even from very early stages in life, alter the responses and behavior toward further “painful” experiences and events Hence, no two people experience pain the same way, which adds to the complexity of the management of pain Unfortunately, even when pain is obvious, children frequently receive no or inadequate treatment for pain and painful procedures The newborn and critically ill child are especially vulnerable to receiving no treatment or undertreatment.4,5 The conventional notion that children neither respond to nor remember painful experiences to the same degree that adults is inaccurate Many of the nerve pathways essential for the transmission and perception of pain are present and functioning by 24–29 weeks of gestation.6,7 Research in newborn animals has revealed that failure to provide analgesia for pain results in “rewiring” of the nerve pathways responsible for pain transmission in the dorsal horn of the spinal cord, resulting in increased pain perception of future painful insults This confirms human newborn research that found that the failure to provide anesthesia or analgesia for newborn circumcision resulted not only in short-term physiologic perturbations but also in longer-term behavioral changes.8,9 Hadzic_Ch45_p848-862.indd 848 Nurses are traditionally taught or cautioned to be wary of physicians’ orders and patients’ requests for pain management, as well The most common prescription order for potent analgesics, “to give as needed” (pro re nata, PRN), in reality means “to give as infrequently as possible.” The PRN order also means that either the patient must know or remember to ask for pain medication or the nurse must be able to identify when a patient is in pain Neither requirement may be met by children in pain Children less than years of age and critically ill children may be unable to adequately verbalize when they are in pain or where they hurt Moreover, they may be afraid to report their pain Several studies have documented the inability of nurses, physicians, and parents/guardians to correctly identify and treat pain, even in postoperative pediatric patients Societal fears of opioid addiction and lack of advocacy are also causal factors in the undertreatment of pediatric pain Unlike adult patients, pain management in children is often dependent on the ability of parents/guardians to recognize and assess pain and on their decision whether to treat or not Parental misconceptions concerning pain assessment and pain management may therefore also result in inadequate pain treatment Even in hospitalized patients, most of the pain that children experience is managed by their parents/guardians Parents/guardians may fail to report pain either because they are unable to assess it or are afraid of the consequences of pain therapy In one study, false beliefs about addiction and the proper use of acetaminophen and other analgesics resulted in the failure to provide analgesia to children.10 In another, the belief that pain was useful or that repeated doses of analgesics lead to medication underperformance resulted in the failure of the parents/guardians to provide or ask for prescribed 24/02/17 5:26 PM Acute and Chronic Pain Management in Children PAIN ASSESSMENT The perception of pain is a subjective, conscious experience; operationally, it can be defined as “what the patient says hurts” and existing “when the patient says it does.” Infants, preverbal children, and children between the ages of and years may be unable to describe their pain or their subjective experiences This has led many to conclude incorrectly that children not experience pain in the same way that adults Clearly, children not have to know (or be able to express) the meaning of an experience to have an experience Therefore, because pain is essentially a subjective experience, it is becoming increasingly clear that the child’s perspective of pain is an indispensable facet of pediatric pain management and an essential element in the specialized study of childhood pain Sometimes there is an overreliance on objective assessments of pain, whether from a healthcare professional or parental/guardian assessment This objective assessment, though sometimes important, should remain only a minor partner in the assessment and management of pain, as objective assessments are also subject to bias and preconceived notions Indeed, pain assessment and management are interdependent, and one is essentially useless without the other The goal of pain assessment is to provide accurate data about the location and intensity of pain, as well as the effectiveness of measures used to alleviate or eradicate it Instruments currently exist to assess pain in children of all ages.8,12–18 Indeed, the sensitivity and specificity of these instruments have been widely debated and have resulted in a plethora of studies to validate their reliability and validity The most commonly used instruments measure the quality and intensity of pain and are “self-report measures” that make use of pictures or word descriptors to describe pain Pain intensity or severity can be measured in children as young as years of age by using either the Oucher scale (developed by Judith E Beyer, RN, PhD; Antonia M Villarreal, RN, PhD; and Mary J Denyes, RN, PhD)—a two-part scale including both a numeric scale (from to 100) and a photographic scale of six photographs of a young child’s face expressing increasing degrees of discomfort—or a visual analog scale—a 10-cm line with a distraught, crying face at one end and a smiling face at the other The visual analog scale has been validated by both sex and race In our practice, we use the six-face Wong-Baker FACES Pain Rating Scale (developed by Dr Donna Wong and Connie M Baker), primarily because of its simplicity (Figure 45–1).16 This scale is attached to the vital sign record, and nurses are instructed to use it or a more ageappropriate self-report measure whenever vital signs are taken Chapter CHAPTER 45 X analgesics to treat their children’s pain.11 Parental/guardian education is therefore essential if children are to be adequately treated for pain All of these factors make children an extremely vulnerable group Fortunately, the past 25 years have seen substantial advances in research and interest in pediatric pain management and in the development of pediatric pain services, primarily under the direction of pediatric anesthesiologists Pain service teams provide pain management for acute, postoperative, terminal, neuropathic, and chronic pain Nevertheless, the assessment and treatment of pain in children are important aspects of pediatric care, regardless of who provides it Failure to provide adequate control of pain amounts to substandard and unethical medical practice 849 Clinical Pearl • Regular assessment using appropriate pain assessment tools, involving the patient and carers in decision making, and being as flexible as possible to the patient’s needs all play a vital role in achieving a successful outcome Pain assessment in preverbal children poses challenges as they are unable to self-report There are many pain assessment tools available in this age group, but none are ideal The CRIES19 FIGURE 45–1. The six-face Wong-Baker FACES Pain Rating Scale (Wong-Baker FACES Foundation (2015) Wong-Baker FACES® Pain Rating Scale Retrieved January 28, 2017 with permission from http://www.WongBakerFACES.or.) Hadzic_Ch45_p848-862.indd 849 24/02/17 5:26 PM 850 PEDIATRIC ANESTHESIA TABLE 45–1. CRIES pain scale for babies from 32 weeks’ gestational age PART Crying Characteristic cry of pain is high pitched No cry or cry that is not high pitched High-pitched cry but infant is consolable High-pitched cry and infant is inconsolable Requires O2 to maintain SaO2 > 95 Consider other changes in oxygenation No Requires O2 < 30% Requires O2 > 30% Increased vital signs Take BP last as this may cause difficulty with other assessments HR and BP +/– 10% of baseline 10%–20% increase in BP or HR > 20% increase in HR or BP Expression Grimace characterized by brow bulge, eyes shut, open mouth, deepening nasolabial furrow Neutral Grimace Grimace/grunt Sleeplessness Based on state during the hour preceding the assessment No Wakes frequently Constantly awake Instructions: Each of the five categories is scored 0, 1, or 2, resulting in total score between and 10 pain score is frequently used to score pain in neonates (Table 45–1) Children with developmental delay, complex needs, and or in intensive care need special pain assessment tools to monitor pain Most such tools incorporate physiological parameters for stress (cardiac, respiratory, and endocrine) with behavioral changes associated with pain (facial expressions, crying, body and limb movements).20 A separate pain assessment scale called the Paediatric Pain Profile (PPP)21 is available at our institution for use in children with complex needs It is used primarily by parents/guardians to measure their child’s pain and incorporates scoring of the aforementioned behavioral changes Irrespective of the pain assessment tool used in these patient groups, it is important that healthcare professionals understand what causes pain, appreciate that pediatric patients perceive pain, and have a variety of assessment methods and treatments in their armamentarium to achieve effective pain control PAIN MANAGEMENT Acute pediatric pain management is increasingly characterized by a multimodal or “balanced” approach in which smaller doses of opioid and nonopioid analgesics, such as nonsteroidal antiinflammatory drugs (NSAIDs), local anesthetics, N-methyl-Daspartate (NMDA) antagonists, and α2-adrenergic agonists, are combined to maximize pain control and minimize druginduced adverse side effects Pain management also includes management of both patient and parental/guardian expectations and being knowledgeable, open, and frank about what to expect during the course of the postoperative and rehabilitation periods It should be recognized that certain procedures “hurt” more than others and that, in spite of our best efforts, it is not always possible to achieve “no pain,” although that should always be the aim At the same time, preoperative discussion of the various analgesic strategies available and reassurance that Hadzic_Ch45_p848-862.indd 850 the patient “will be looked after” go a long way to achieving a satisfactory outcome for all concerned In addition, a multimodal approach utilizes nonpharmacological, complementary, and alternative medicine therapies, as well These techniques include distraction, guided imagery, transcutaneous nerve stimulation, acupuncture, therapeutic massage, among others.22 Clinical Pearls • The aim of acute pain management is providing a comfortable/pain-free perioperative period in order to facilitate early ambulation and rehabilitation • Preoperative discussions with the patient and his or her parents/guardians detailing the achievable outcome, expected course, and various available pain management modalities play an important role in achieving a satisfactory outcome for all concerned • A multimodal approach to pain management achieves the best results • If possible, regional anesthesia/analgesia should be part and parcel of any multimodal analgesia regime Clinical Pearl Alternative medicine pain therapy: • Distraction • Guided imagery • Transcutaneous nerve stimulation • Acupuncture • Therapeutic massage 24/02/17 5:26 PM Acute and Chronic Pain Management in Children Clinical Pearl They provide pain relief primarily by blocking peripheral and central prostaglandin production by inhibiting cyclooxygenase types I and II These analgesic agents are primarily administered enterally via the oral or rectal route and are particularly useful for inflammatory, bone, and rheumatic pain Parenterally administered acetaminophen and NSAIDs, such as ketorolac, are available for use in children in whom the oral or rectal routes of administration are not possible.26 Unfortunately, regardless of dose, the nonopioid analgesics reach a “ceiling effect,” above which pain cannot be relieved by these drugs alone Because of this, these weaker analgesics are considered the basic building blocks in a multimodal therapeutic approach and are often administered in combination forms with opioids such as codeine, oxycodone, hydrocodone, or tramadol Aspirin has been largely abandoned in pediatric practice because of its possible role in Reye syndrome, its effects on platelet function, and its gastric irritant properties Chapter CHAPTER 45 X Procedural pain is often a forgotten and ignored aspect of pain management in children admitted to hospital Various interventions and procedures, some of which are done repeatedly, may inflict pain or are perceived as painful by an anxious child (eg, cannulation, phlebotomy, lumbar puncture, and wound dressing and cleaning) It is essential to practice how to explain procedures and how to prepare and reassure the child and parents/guardians Simple techniques such as local anesthetic creams and play/distraction therapy can help in many situations Some patients may also need formal psychological intervention and support or pharmacological aids such as sedation or nitrous oxide (N2O), all of which require time and planning Lastly, if conscious sedation or N2O is required, adequate monitoring and emergency equipment, including oxygen, suction, and appropriate personnel, should be immediately available Pain management strategies for day case surgery should include local anesthetic infiltration, regional blocks, simple analgesics (eg, acetominophen/paracetamol, NSAIDS, and “milder” opioids such as codeine or tramadol, if necessary) “Strong” opioids should be avoided, although they are not contraindicated Ultrasound-guided regional anesthesia is increasing in popularity, providing safer and more effective regional anesthesia 851 Clinical Pearls • The nonopioid analgesics have a “ceiling effect,” above which pain cannot be relieved by these drugs alone, regardless of dose • Nonopioid analgesics are considered the basic building blocks in a multimodal therapeutic approach and are often administered in combination forms with opioids such as codeine, oxycodone, hydrocodone, or tramadol Pain management strategies for day case surgery: • Local anesthetic infiltration • Regional anesthesia • Nonopioid analgesics (acetaminophen, NSAIDs) • Mild opioids (codeine, tramadol) when necessary • More potent opioids should be avoided when possible but are not contraindicated Anesthesiologists must work closely with surgical colleagues to identify appropriate day case surgeries and develop patient care pathways with standard analgesia management plans for specific procedures For major surgery, in addition to all the above mentioned analgesics, opioid and/or local anesthetic infusions may be necessary These can be complemented by other treatment modalities including ketamine, clonidine, or diazepam for muscle spasm after orthopedic surgeries; gabapentin for acute pain; intraoperative magnesium; and the addition of dexamethasone systemically or to a local anesthetic for nerve blocks ■■ Analgesics with Antipyretic Activity or Nonopioid (“Weaker”) Analgesics The “weaker” or milder analgesics with antipyretic activity, of which acetaminophen, ibuprofen, naproxen, and diclofenac are the classic examples, make up a heterogeneous group of NSAIDs that are nonopioid analgesics (Table 45–2).23–25 Hadzic_Ch45_p848-862.indd 851 The most commonly used nonopioid analgesic in pediatric practice remains acetaminophen Unlike NSAIDs, acetaminophen works primarily centrally and has minimal, if any, anti-inflammatory activity When administered in normal doses (10–15 mg · kg–1, PO), acetaminophen is extremely safe and has very few serious side effects It is an antipyretic and, like all enterally administered NSAIDs, takes about 30 minutes to provide effective analgesia Several investigators have reported that when administered rectally, acetaminophen should be given in significantly higher doses than previous recommendations had suggested.27,28 However this author does not use acetaminophen loading doses when the drug is administered rectally Regardless of route of delivery, to prevent hepatotoxicity, the daily maximum acetaminophen dose in the preterm neonate, term neonate, and older child is 30, 60, and 80 mg/kg, respectively (Table 45–3) The maximum adult dose is g/day The discovery of at least two cyclooxygenase (COX) isoenzymes, referred to as COX-1 and COX-2, has increased our knowledge of NSAIDs.29–32 These two COX isoenzymes share structural and enzymatic similarities but are uniquely regulated at the molecular level and may be distinguished by their functions Protective prostaglandins, which preserve the integrity of the stomach lining and maintain normal renal function in a compromised kidney, are synthesized by COX-1.29,30,33 COX-2 is an inducible isoform The inducing stimuli include proinflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and control of cell growth In 24/02/17 5:26 PM 852 PEDIATRIC ANESTHESIA TABLE 45–2. Dosing guidelines for commonly used nonopioid analgesics (Institutional or national guidelines may vary.) PART Premature Neonates (32–36 weeks Postmenstrual Agea) Acetaminophen (Paracetamol) Term Neonates (> 36–44 weeks Postmenstrual Agea) Infants and Children (> 44 weeks Postmenstrual Agea and up to 50 kg) > 12 Years (and Weight > 50 kgb) Acetaminophen (Paracetamol) 15 mg/kg PO/PR every hours (max 60 mg/kg/day) 15 mg/kg PO/PR every hours (max 60 mg/kg/day) 15–20 mg/kg PO/PRbc every 4–6 hours (max 90 mg/kg/day) 1g PO/PR every 4–6 hours (max g/day) IV acetaminophen 7.5 mg/kg IV every hours (max 25 mg/kg/day) 7.5 mg/kg IV every hours (max 30 mg/kg/day) 15 mg/kg IVb every hours (max 60mg/kg/day) 15 mg/kg IV (maximum g) every hours Nonsteroidal anti-inflammatory drugs (NSAIDs) Prescribe one drug only Ibuprofen Not recommended Not recommended Less than months of age: mg/kg PO every hours 400 mg PO every hours From months of age: 10 mg/kg PO (maximum 400 mg) every hours (max 30 mg/kg/day) Diclofenac Not recommended Not recommended From months of age: mg/kg PO/PR every hours 50 mg PO/PR every hours Naproxen Not recommended Not recommended mg/kg every 12 hours 5mg/kg every 12 hours (max 1g/day) Postmenstrual age in weeks is the gestational age plus the postnatal age (time elapsed after birth) Doses based on weight in obese patients or based on age in underweight patients may need to be reduced to avoid overdosage c A higher dose of acetaminophen 20 mg/kg PO/PR every hours may be used when pain is not controlled with the standard dose (15 mg/kg) when no contraindications exist This dose should be reviewed every 24 hours Loading doses are not recommended in order to minimize the potential for error a b addition to the induction of COX-2 in inflammatory lesions, COX-2 is present constitutively in the brain and spinal cord, where it may be involved in nerve transmission, particularly for pain and fever Prostaglandins made by COX-2 are also important in ovulation and in the birth process.28,29,31 The discovery of COX-2 has made possible the design of drugs that reduce inflammation without removing the protective prostaglandins in the stomach and kidney made by COX-1 In fact, developing a more specific COX-2 inhibitor has been an important goal of much drug research because this class of drug has all of the antiinflammatory and analgesic properties that one desires in a Hadzic_Ch45_p848-862.indd 852 drug with none of the gastrointestinal and antiplatelet side effects Unfortunately, the growing controversy regarding the potential adverse cardiovascular risks of the prolonged use of COX-2 inhibitors has dampened much of the enthusiasm for these drugs and has led to the removal of rofecoxib from the market by its manufacturer.34,35 Other NSAIDs, especially diclofenac, are now facing similar scrutiny Many orthopedic surgeons are also concerned about the negative effect of all NSAIDs on bone growth and healing.36–38 While some pediatric orthopedic surgeons have recommended that these drugs not be used in their patients in the postoperative period, it is this 24/02/17 5:26 PM Hadzic_Ch45_p848-862.indd 853 TABLE 45–3. Opioid analgesic initial dosage guidelines (institutional or national guidelines may vary.) Drug Codeine Equianalgesic Dose (mg) IV, IM, SC Oral 120 200 Usual Starting IV Dose and Interval < 50 kg > 50 kg NR NR Usual Starting Oral Dose and Interval < 50 kg > 50 kg a 0.5–1 mg/kg 0.5–1a every mg/kg every 4-6 hours 4–6 hours Fentanyl 0.1 NAb Bolus: 0.5–1 mcg/kg, 0.5–2 h (max 50 mcg) NCA/PCA (drug concentration: mcg/kg/mL, max 50 mcg/mL) NCA: Bolus: 0.5–1 mcg/kg, 30 min–1 h; infusion: 0.5–1 mcg/kg/h PCA: Bolus: 0.5 mcg/kg, 10 min–1 h; infusion: 0.5–1 mcg/kg/h NA NA NA Hydrocodone NA 10–20 NA NA NA 0.1 mg/kg every 3–4 hours 5–10 mg every 3–4 hours Hydromorphone 1.5–2 3–5c Bolus: 0.02 mg/kg, 0.5–2 h; infusion: 0.004 mg/kg/h Bolus: mg, 0.5–2 h; infusion: 0.3 mg/h 1:2 0.03–0.08 mg/kg every hours 2–4 mg every hours Methadone 10 10–20 0.1 mg/kg every 4–8 hours 5–10 mg every 4–8 hours 1:2 0.2 mg/kg every 4–8 hours 10 mg every 4–8 hours Morphine 10 30–50 Bolus: 0.03–0.1 mg/kg, 0.5–2 h (max 10 mg) NCA/PCA(drug concentration 20mcg/kg/mL, max 1mg/mL)d NCA: Bolus: 20 mcg/kg, 15 min–1 h; infusion: 20 mcg/kg/h PCA: Bolus: 20 mcg/kg (max mg), 5min; infusion: mcg/kg/h 1:2–3 0.2–0.3 mg/kg every 4–6 hours Sustained release: 0.4–0.5 mg/kg every 8–12 hours 15 mg/kg every 4–6 hours Sustained release: 30 mg every 8–12 hours Oxycodone NA 10–20 NA NA 0.1 mg/kg every 3–4 hours 5–10 mg every 3–4 hourse NA Due to the highlighted problem with “ultra-rapid metabolizers,” it is best to start with a dose of 0.5 mg/kg Oral transmucosal route available: dose 10–15 mcg/kg c The equianalgesic oral dose and parenteral/oral dose ratio are not well established d For neonates and infants younger than 13 weeks, the drug concentration is to be halved: bolus mcg/kg,1 h; infusion 5–10 mcg/kg/h e A sustained-release preparation is available a b Acute and Chronic Pain Management in Children IV/Oral Ratio 1:2 853 Chapter CHAPTER 45 X 24/02/17 5:26 PM 854 PEDIATRIC ANESTHESIA author’s view that in spite of the controversies, NSAIDs remain effective and useful drugs in pediatric acute pain management when used wisely and for short duration PART ■■ Opioid Drug Selection Many factors are considered when deciding which is the appropriate opioid analgesic to administer to a pediatric patient in pain These include pain intensity, patient age, coexisting disease, potential drug interactions, treatment history, physician preference, patient preference, and route of administration Some opioids are preferred over others, and some may be unavailable depending on institution, country, or continent, for reasons not entirely understood The idea that some opioids are “weak” (eg, codeine) and others “strong” (eg, morphine) is outdated All are capable of treating pain regardless of intensity if the dose is adjusted appropriately (Table 45–4) At equipotent doses, most opioids have similar effects and side effects Meperidine (pethidine) at an equianalgesic dose has the same side effect profile as morphine;39 however, it is no longer commonly prescribed ■■ Commonly Used Oral Opioids: Codeine, Oxycodone, Hydrocodone, Morphine, and Tramadol Codeine, oxycodone, and hydrocodone are opioids that are frequently used to treat pain in children and adults, particularly less severe pain and when patients are being converted from parenteral to enteral opioids (see Table 45–3) Morphine is commonly used in regimens for chronic pain (eg, cancer) Codeine, oxycodone, and hydrocodone are most commonly administered in oral form, usually in combination with acetaminophen or aspirin.40 Unfortunately, very few, if any, pharmacokinetic or dynamic studies have been performed in children, and most dosing guidelines are anecdotally based In equipotent doses, codeine, oxycodone, hydrocodone, and morphine are equal both as analgesics and respiratory depressants (see Table 45–3) In addition, these drugs share common effects on the central nervous system with other opioids, including sedation, respiratory depression, and stimulation of the chemoreceptor trigger zone in the brain stem, the latter particularly the case for codeine There are fewer nausea and vomiting side effects with oxycodone and hydrocodone Codeine, hydrocodone, and oxycodone have a bioavailability of approximately 60% after oral ingestion The analgesic effects occur as early as 20 minutes after ingestion and reach a maximum after 60–120 minutes The plasma half-life of elimination is 2.5–4 hours Codeine undergoes nearly complete metabolism in the liver before its final excretion in urine Approximately 10% of codeine is metabolized into morphine (CYP2D6), and it is this 10% that is responsible for codeine’s analgesic effect Interestingly, approximately 10% of the population and most newborn infants cannot metabolize codeine into morphine, and in these patients, codeine produces little, if any, analgesia Codeine needs special mention, as its use has come under increased scrutiny at the time of writing this chapter A few instances of fatalities and life-threatening episodes of respiratory depression have been reported in children who are cytochrome P450 CYP2D6 “ultra-rapid metabolizers” and were given codeine after tonsillectomy or adenoidectomy in the treatment of obstructive sleep apnea.41,42 The CYP2D6 enzyme is subject to genetic polymorphism Having multiple gene copies, some patients metabolize codeine more rapidly (and are thus termed “ultra-rapid metabolizers”) and therefore have an increased risk of experiencing morphine toxicity, ie, respiratory depression The prevalence of this varies with ethnicity, from as low as 0%–2% in Asians to as high as 10%–16% in Ethiopians and Saudi Arabians.43 The current position on codeine use is as follows The U.S Federal Drug Administration (FDA),44 the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA),45 and the U.K Medicines and Healthcare Products Regulatory Agency (MHRA) have recommended restrictions on the use of codeine in children These include the following: • Restrict the use of codeine to children over 12 years of age (EMA and MHRA) • Avoid codeine use in patients under 18 years of age who are undergoing tonsillectomy or adenoidectomy, especially for obstructive sleep apnea (EMA and FDA) TABLE 45–4. Maximum local anesthetic dosing guidelines Drug Bupivacainea Dose mg/kg Without Epinephrine 2.5 Dose mg/kg with Epinephrine Duration in Hours 3–6 Chloroprocaineb 10 Lidocaine Ropivacainec Contra-Indications Comments Reduce dose by 50% in neonates Plasma cholinesterase deficiency Short-acting, rapid metabolism, useful in neonates and possibly patients with seizures or liver disease never mixed 3–6 Less cardiotoxicity than bupivacaine When given by epidural continuous infusion: 0.2–0.4 mg/kg/h In neonatal epidural continuous infusion: 10–15 mg/kg/h c Infusion rates is 0.5 mg/kg for pediatric patients older than 4-6 months of age a b Hadzic_Ch45_p848-862.indd 854 24/02/17 5:26 PM Acute and Chronic Pain Management in Children For many years codeine has been more or less universally used in pediatric practice for the relief of moderate pain, as a stepdown medication, and as a take-home medication on discharge Possible dilemmas include the following: • Due to its widespread use, various “child-friendly” preparations and formulations exist to provide versatile delivery systems for all ages However, recent developments may have led to discouraging the development of versatile formulations of other similar-“strength” opioids Thus, many countries are left with limited or no suitable alternatives to codeine • Licensing and use of alternative drugs is lagging in certain countries For instance, tramadol is not licensed in the U.K for patients below 12 years of age • There are few data to determine if any the available alternatives are as effective as codeine.46 • Although morphine is the most logical alternative to codeine, issues of concern include controlled drug regulations in certain countries, institutional and local practices, and the reluctance of some healthcare professionals to prescribe oral morphine due to social concerns and the perceived potential for abuse • For institutions and countries where other safe, effective, and versatile formulations of codeine alternatives, such as tramadol, oxycodone, and buprenorphine, are available, local interim guidelines may need to be agreed upon (with or without the continued use of codeine) in order to continue to provide safe and effective analgesia to the pediatric population • These issues may encourage pharmaceutical companies to develop more “child-friendly” analgesic products and encourage similar research of other opioids to validate their efficacy in children • These concerns may also lead to the development of commercially viable patient genotyping Like codeine and oxycodone, morphine is very effective when given orally, but only about 40% of an oral dose of morphine reaches the systemic circulation In the past, this led many to inappropriately conclude that morphine is ineffective when administered orally; instead, the lack of efficacy was simply the result of inadequate PO dosing Therefore, when converting a patient’s required intravenous morphine dose to an oral maintenance dose, one must multiply the intravenous dose by a factor of to Clinical Pearl • When converting a patient’s required intravenous morphine dose to an oral maintenance dose, multiply the intravenous dose by a factor of to Hadzic_Ch45_p848-862.indd 855 Whereas oral morphine is prescribed alone, oral codeine, hydrocodone, oxycodone, and tramadol are usually prescribed in combination with either acetaminophen or aspirin Acetaminophen potentiates the analgesia produced by codeine (and other opioids) and allows the use of a smaller dose of the opioid with satisfactory analgesia In all “combination preparations,” beware of inadvertently administering a hepatotoxic dose of acetaminophen when increasing opioid doses for uncontrolled pain.47 Because of this concern, it is preferred to prescribe the opioid and acetaminophen (or ibuprofen) separately Although it is an effective analgesic when administered parenterally, intramuscular codeine has no advantage over morphine or any other opioid; hence, its use is discouraged Similar to codeine, tramadol is used to treat moderate to severe pain Although tramadol is often categorized as a μ-receptor agonist, it has multiple proposed mechanisms of action It is also a serotonin releaser, a norepinephrine reuptake inhibitor, and an NMDA receptor antagonist The licensing age of tramadol varies by country, but it has been studied in children as young as year.48 Tramadol is prescribed in a dose of 1–2 mg/kg every hours to a maximum of 400 mg/day (in divided doses for patients over 50 kg) Hydrocodone is prescribed in a dose of 0.05–0.1 mg/kg An elixir is available as 2.5 mg/5 mL combined with acetaminophen 167 mg/5 mL As a tablet, it is available in hydrocodone doses between 2.5 mg and 10 mg, combined with 500–650 mg acetaminophen Oxycodone is prescribed in a dose of 0.05–0.1 mg/kg Unfortunately, an elixir is not available in most pharmacies When it is, it is prepared as either mg/mL or 20 mg/mL This can obviously result in catastrophic dispensing errors In tablet form, oxycodone is commonly available as a 5-mg tablet or as Tylox (500 mg acetaminophen and mg oxycodone) or Percocet (325 mg acetaminophen and mg oxycodone) Oxycodone is also available without acetaminophen in a sustained-release tablet for use in chronic pain Like many other timed-release tablets, it must not be crushed and therefore cannot be administered through a gastric tube Breaking the tablet results in the immediate release of a huge amount of oxycodone Like sustained-release morphine (see below), sustainedrelease oxycodone is only for use in opioid-tolerant patients with chronic pain, not for routine postoperative pain Also, note that in patients with rapid gastrointestinal transit, sustained-release preparations may not be absorbed at all (liquid methadone may be an alternative) Oral morphine is available as a liquid in various concentrations (as much as 20 mg/mL), a tablet (eg, MSIR [morphine sulfate immediate release], available in 15- and 30-mg tablets), and in a sustained-release preparation Because it is so concentrated, the liquid is particularly easy to administer to children and severely debilitated patients Indeed, in terminal patients who cannot swallow, liquid morphine provides analgesia when simply dropped into the patient’s mouth.40 Chapter CHAPTER 45 X • In all other cases, use codeine only if required It should be prescribed on an “as-needed basis” only, with the dose restricted to 0.5 mg/kg (maximum 30 mg) every hours, and limited in treatment duration • Patient receiving codeine should be closely monitored for respiratory depression; nurses and parents/guardians should be advised to watch for signs of morphine overdose 855 ■■ Patient- and Parent/ Nurse-Controlled Analgesia Among the many reasons for the undertreatment of pediatric pain is the lack of familiarity of physicians (and nurses) with 24/02/17 5:26 PM 856 PEDIATRIC ANESTHESIA PART appropriate drugs, drug dosing, and routes of administration When drugs are given on demand (PRN), there is a lag between the time of the patient’s request and the nurse’s response and the preparation and administration of analgesia In moderate to severe pain, around-the-clock administration interval administration (eg, q4h) is not always the answer either, however, because of the great individual variation in pain perception and opioid metabolism Indeed, fixed doses and time intervals make little sense Based on the pharmacokinetics of opioids, it should be clear that intravenous boluses of morphine may need to be given at intervals of 1–2 hours to avoid marked fluctuations in plasma drug levels Continuous intravenous infusions may provide steady analgesic levels, are preferable to intramuscular injections, and have been used with great safety and effectiveness in children However, they are not a panacea because the perception and intensity of pain are not constant For example, a postoperative patient may be very comfortable resting in bed and require little adjustment in pain management But this same patient may experience excruciating pain when coughing, voiding, or getting out of bed Thus, rational pain management requires some form of titration to effect whenever any opioid is administered To give patients (in some cases nurses and, rarely, parents/ guardians) some measure of control over pain therapy, demand analgesia, or patient-controlled analgesia (PCA), devices have been developed.49,50 These devices are microprocessor-driven pumps with a button that the patient presses to self-administer a small dose of opioid PCA devices allow patients to administer small amounts of an analgesic whenever they feel a need for more pain relief The opioid, usually morphine, hydromorphone, or fentanyl, is administered either intravenously or subcutaneously The dosage of opioid (with or without background infusion), number of boluses per hour, and the time interval between boluses (the “lockout period”) are programmed into the equipment by the pain service physician or nurse to allow maximum patient flexibility and a sense of control with minimal risk of overdosage Generally, when older patients know that if they have severe pain, they can obtain relief immediately, many prefer dosing regimens that result in mild to moderate pain in exchange for fewer side effects such as nausea or pruritus Typically, morphine is prescribed, 20 mcg/kg per bolus (or hydromorphone 3–4 mcg/kg/h or fentanyl 0.5 mcg/kg/h), with a 5- to 15-minute lockout interval between each bolus Variations include larger or smaller boluses, shorter or longer time intervals, and varying background infusion; these tend to be based on institutional practice and preferences The PCA pump computer stores within its memory the number of boluses the patient has received as well as the number of attempts the patient has made to receive boluses This allows the physician to evaluate how well the patient understands the use of the pump and provides information to program the pump more efficiently Most PCA units allow low “background” continuous infusions (eg, morphine 2–30 mcg/ kg/h, hydromorphone 3–4 mcg/kg/h, fentanyl 0.5-1 mcg/ kg/h) in addition to self-administered boluses A continuous background infusion is particularly useful at night and often Hadzic_Ch45_p848-862.indd 856 provides more restful sleep by preventing the patient from awakening in pain However, it also increases the potential for overdosage.49–51 Although the adult literature on pain does not support the use of continuous background infusions, our experience has been that continuous infusions are essential for good pain management in the pediatric patient Indeed, in our practice, we almost always use continuous background infusions when we prescribe PCAs or nurse-controlled analgesia (NCA) PCA requires a patient with enough intelligence, manual dexterity, and strength to operate the pump Thus, these devices were initially limited to adolescents, but the lower age limit in whom this treatment modality can be used continues to fall (currently around age 5–6 years) Contraindications to the use of PCA include inability to push the bolus button, inability to understand how to use the machine, and patient desire not to assume responsibility for his or her care In patients considered below “competent” age, neonates, toddlers, and patients with complex needs, the practice of allowing surrogates such as nurses to initiate a PCA bolus is called nurse-controlled analgesia (NCA) This is standard practice in our institution It has been demonstrated that nurses and, in rare cases, parents can be empowered to initiate PCA boluses and to use this technology safely in children, even in those younger than year of age, the incidence of common opioid-induced side effects being similar to that observed in older patients.51 NCAs tend to have a slightly higher background infusion rate and longer lockout period than PCAs For neonates and infants 1–3 months old, we use NCA morphine: a background infusion of or 10 mcg/kg/h, respectively, with a bolus of mcg/kg and a lockout of 60 minutes Interestingly, respiratory depression is very rare, but does occur, reinforcing the need for close monitoring and established nursing protocols Difficulties with PCA include its increased cost, patient age limitations, and the bureaucratic obstacles (protocols, nurse education, storage arrangements) that must be overcome before its implementation ■■ Transmucosal, Intranasal, and Transdermal Fentanyl Because fentanyl is extremely lipophilic, it can be readily absorbed across any biologic membrane, including the skin Thus, it can be given painlessly by new, nonintravenous routes of drug administration, including the transmucosal (nose and mouth) and transdermal routes The transmucosal route of fentanyl administration is extremely effective for acute pain relief When given intranasally (2 mcg/kg), it produces rapid analgesia that is equivalent to intravenously administered fentanyl.52 Alternatively, fentanyl has been manufactured in a candy matrix (Actiq) attached to a plastic applicator (it looks like a lollipop) for transoral/transmucosal absorption As the child sucks on the candy, fentanyl is absorbed across the buccal mucosa and is rapidly (over 10–20 minutes) absorbed into the systemic circulation.53–58 If excessive sedation occurs, the fentanyl is removed from the child’s mouth by the applicator This method is more efficient than ordinary oral–gastric intestinal administration because transmucosal absorption bypasses the 24/02/17 5:26 PM Acute and Chronic Pain Management in Children Hadzic_Ch45_p848-862.indd 857 (E-Trans, Alza Corporation).63 Transdermal PCA may offer logistic advantages for patients and nursing staff by eliminating the need for venous access, IV tubing, and specialized pumps ■■ Complications Regardless of method of administration, all opioids produce common unwanted side effects, such as pruritus, nausea and vomiting, constipation, urinary retention, cognitive impairment, tolerance, and dependence.64 Indeed, many patients suffer needlessly from agonizing pain because they would rather suffer pain than experience these opioid-induced side effects.65 In addition, physicians are often reluctant to prescribe opioids because of these side effects and because of their fear of other less common, but more serious, side effects such as respiratory depression Several clinical and laboratory studies have demonstrated that low-dose naloxone infusions (0.25–1 mcg/kg/h) can treat or prevent opioid-induced side effects without affecting the quality of analgesia or opioid requirements.66,67 Some opioids, when given concomitantly with selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs), or serotonin–norepinephrine reuptake inhibitors (SNRIs), have been associated with serotonin syndrome; these include fentanyl, oxycodone, hydrocodone, and tramadol Chapter CHAPTER 45 X efficient first-pass hepatic metabolism of fentanyl that occurs after enteral absorption into the portal circulation Actiq has been approved by the FDA for use in children for premedication before surgery and for procedure-related pain (eg, lumbar puncture, bone marrow aspiration).59 It is also useful in the treatment of cancer pain and as a supplement to transdermal fentanyl.60 When administered transmucosally, fentanyl is given in doses of 10–15 mcg/kg, is effective within 20 minutes, and lasts approximately hours Approximately 25%–33% of the given dose is absorbed Thus, when administered in doses of 10–15 mcg/kg, blood levels equivalent to 3–5 mcg/kg IV fentanyl are achieved The major side effect, nausea and vomiting, occurs in approximately 20%–33% of patients who receive it.61 The transdermal route is frequently used to administer chronically administered drugs, including scopolamine, clonidine, and nitroglycerin Many factors, such as body site, skin temperature, skin damage, ethnic group, and age, affect the absorption of transdermally administered drugs Placed in a selective semipermeable membrane patch, a reservoir of drug provides slow, steady-state absorption of drug across the skin The patch is attached to the skin by a contact adhesive, which often causes skin irritation The use of transdermal fentanyl has revolutionized adult cancer pain management As fentanyl is painlessly absorbed across the skin, a substantial amount is stored in the upper skin layers, which then acts as a secondary reservoir The presence of a skin depot has several implications: it dampens the fluctuations of fentanyl effect, it needs to be reasonably filled before significant vascular absorption occurs, and it contributes to a prolonged residual fentanyl plasma concentration after patch removal Indeed, the amount of fentanyl remaining within the system and skin depot after patch removal is substantial At the end of a 24-hour period, approximately 30% of the total delivered dose from the patch remains in the skin depot Thus, removing the patch does not stop the continued absorption of fentanyl into the body.62 Because of the long onset time, inability to rapidly adjust drug delivery, and long elimination half-life, the use of transdermal fentanyl for acute pain management is controversial As stated above, the safety of this drug delivery system is compromised even further because fentanyl continues to be absorbed from the subcutaneous fat for almost 24 hours after the patch is removed In fact, the use of this drug delivery system for acute pain has resulted in the death of an otherwise healthy patient Transdermal fentanyl is generally reserved for patients with chronic pain (eg, cancer) and those who are opioid tolerant Even when transdermal fentanyl is appropriate, the vehicle imposes its own constraints The lowest-dose fentanyl “patch” delivers 25 mcg fentanyl per hour; the others deliver 50, 75, and 100 mcg of fentanyl per hour Patches cannot be physically cut into smaller pieces to deliver less fentanyl This often limits usefulness in patients with lower body weights, and, as with other opioids, this drug delivery system has neither been tested nor approved for use in children A new noninvasive method of transdermal PCA is on the horizon Using iontophoresis (electrotransport), small doses of fentanyl (40 mcg) can be self-administered across the skin 857 ■■ Transition to Oral Medication Successful transition from intravenous (or epidural) analgesics to oral medication depends on the clinician’s ability to provide alternative therapy that is palatable, acceptable, and above all, equally effective in treating pain There are many advantages in providing pain medication by the oral route Enteral therapy consists of a less invasive route of drug administration and enables children to more rapidly return to their normal lives Moreover, oral medications are easier and less expensive to deliver than IV and epidural drugs Certain criteria are essential for the successful transition to oral medication Normal gastrointestinal function must be present before attempting enteral therapy Thus, the child must be able to drink and/or eat (or have a functioning gastric tube) A child who is nauseated or vomits after eating will simply not tolerate oral analgesics Second, severe pain is difficult, if not impossible, to control with oral analgesics alone Therefore, oral analgesics should be reserved for the treatment of mild to moderate pain during the latter part of the recovery process Assessment of the degree of pain and existing treatment modalities are steps that aid the transition process Third, an oral formulation that is palatable and appropriate must be available Finally, one must convert the current parenteral opioid dosing to a roughly equianalgesic oral dose This conversion is fairly straightforward even when patients are receiving multiple forms and doses of parenteral opioids As a first step, convert the entire daily dose of administered opioids into IV morphine equivalents (Example 1) Then, convert that morphine dose to an equianalgesic dose of oral morphine (1:2) or other oral opioid, if desired This formula actually underestimates the bioequivalence of the drugs but is used to minimize the risk of overdose during the transition 24/02/17 5:26 PM 858 PEDIATRIC ANESTHESIA Example PART A 5-year-old, 20-kg boy was the victim of a motor vehicle accident and sustained a pelvic fracture He has been on IV PCA morphine for weeks and will be discharged home for further outpatient therapy and recovery He receives morphine mg/h and averages one bolus of 0.5 mg morphine every hour He cannot swallow pills Step 1: mg/h for 24 hours = 48 mg morphine/24 hours Step 2: 0.5 mg/bolus for 24 boluses/day = 12 mg morphine Step 3: Total 24-hour morphine = 48 mg + 12 mg = 60 mg Step 4: 60 mg IV morphine = 120 mg PO morphine (actually, this represents a 25%–40% decrease in bioequivalence) Step 5: Prescribe oral morphine 20 mg every hours and an analgesic with antipyretic activity (eg, acetaminophen or ibuprofen) Step 6: Stop the basal opioid infusion (PCA) immediately or concomitantly with oral dose; increase oral dose by 20%–25% if pain relief is deemed inadequate If the opioid requirement is high, PCA can be used to provide “rescue” boluses only for the period of transition or to wean the background infusion/PCA doses to more manageable oral doses with neuroaxial blockade To be used safely, a working knowledge of anatomy, limitations of technique, and differences in how local anesthetics are metabolized in infants and children is necessary All aspects of local anesthetics are discussed in detail in previous chapters ■■ Other Adjutants in a Multimodal Analgesia Regime Gabapentin Gabapentin is well established in chronic pain management A few studies have shown that perioperative gabapentin reduces acute postoperative opioid consumption73 in patients undergoing a variety of surgeries, including coronary artery bypass74 and knee arthroplasty.75 In one study, gabapentin was shown to reduce perioperative opioid use but not opioid-related side effects in pediatric patients undergoing posterior spinal fusion.76 Dosing varies from a single perioperative dose to treatment for 1–2 weeks At our institution, we use gabapentin for spinal fusion surgeries and selected surgeries where postoperative pain relief is deemed challenging We normally administer gabapentin at a dose of 5–10 mg/kg every hours for days For patients with complex needs, doses may need to be revised down, as in some cases, gabapentin can produce noticeable sedation or drowsiness ■■ Local Anesthetics Ketamine Over the past 25 years, the use of local anesthetics and regional anesthetic techniques in pediatric practice has undergone a dramatic change Unlike most drugs used in medical practice, local anesthetics must be physically deposited at their site of action by direct application This requires patient cooperation and the use of specialized needles and equipment; because of this, children were long considered poor candidates for regional anesthetic techniques because of their overwhelming fear of needles However, once it was recognized that regional anesthesia could be used as an adjunct, and not as a replacement for general anesthesia, its use has increased exponentially Regional anesthesia offers the anesthesiologist and pain specialist many benefits It modifies the neuroendocrine stress response, provides profound postoperative pain relief, ensures a more rapid recovery, and may shorten the hospital stay Furthermore, because catheters placed in the epidural, upper or lower extremity, or lumbar plexi can be used for days or months, local anesthetics are increasingly being used not only for postoperative pain relief but also for medical (eg, sickle cell vaso-occlusive crisis), neuropathic, and terminal pain relief.68–72 These techniques range from simple infiltration of local anesthetics to neuraxial blocks (eg, spinal and epidural analgesia) With the use of ultrasound guidance, regional anesthesia in the pediatric population has gained further popularity Peripheral nerve blocks can also provide significant pain relief following many common pediatric procedures and have the potential to replace or provide an alternative to “gold standard” epidural treatment This is particularly true in the neonatal population where paravertebral block for a thoracotomy or a transverse abdominis plane (TAP) block for a laparotomy can replace an epidural for effective pain relief and avoid the risks associated Ketamine is a well-known anesthetic that produces dissociative anesthesia but also provides a very good-quality analgesia at very low doses via its NMDA receptor antagonist activity Healthcare professionals remain wary of ketamine, however, due to its unpleasant side effect of hallucinations and its recent implication in neuroapoptosis in the developing brain.77,78 These concerns have now led to the avoidance of ketamine use in patients under year of age and has also decreased the popularity of ketamine as an additive in caudal and epidural blocks However, in older children and adolescents, ketamine is still widely used with good effect Ketamine can also be added to morphine PCA in a 1:1 ratio At our institution, a single low dose of ketamine (0.1–0.25 mg/kg) forms part of a balanced intraoperative analgesic regime for adenotonsillectomy and major surgeries Ketamine infusion is also used as a second-line IV analgesic for complex and painful conditions and in cases of acute or chronic pain where other treatments have failed to produce effective analgesia The infusion dose of ketamine used is 0.05–0.2 mg/kg/h (using a drug concentration of 0.1 mg/kg/mL, up to a maximum of 250 mg in 50 mL) Hadzic_Ch45_p848-862.indd 858 Magnesium Magnesium is used in variety of medical emergencies and treatments The intravenous use of magnesium has been reported to improve postoperative analgesia Though the mechanism of action is not yet fully understood, the analgesic properties of magnesium are believed be due to the regulation of calcium influx into the cell and NMDA receptor antagonist activity.79,80 Evidence has been equivocal, however, and although relatively safe, magnesium is not without side effects A recent meta-analysis concluded that perioperative 24/02/17 5:26 PM Acute and Chronic Pain Management in Children CHRONIC PAIN MANAGEMENT THE TRANSITION FROM ACUTE TO CHRONIC PAIN Acute pain has evolved as a vital defense mechanism, alerting the animal to injury and physical harm in order to stop the exposure to injury, such as with the pain reflex or to signal the need for rest to allow healing to occur Chronic pain, however, serves no protective function Chronic pain is considered to be pain that extends beyond the expected period of healing.82 There are increasing studies in the adult literature demonstrating the development of postoperative chronic pain, which is then associated with significant negative consequences for the individual, in terms of both physical and mental health, and for the wider society, in terms of both economic and healthcare resource burdens The incidence of chronic postoperative pain varies depending on surgery type, with estimates between 5% and 50% in the most common surgical procedures,83 including hernia repair, hip replacement, and cholecystectomy, versus up to 85% in amputations Although the literature for the development of chronic pain postoperatively is sparse in pediatric age ranges, studies are beginning to indicate that it does occur, although its incidence may be lower than in the adult population Fortier83 studied 113 children between the ages of and 17 years who had undergone general urological or orthopedic surgery and found that 13.3% reported chronic pain resulting from surgery The surgeries most related to the development of chronic pain were orthopedic Over one-quarter reported interference in sleep patterns and extracurricular activities, and in reported interference in school activities Chronic pain in adults after inguinal surgery has a reported incidence of 5%–35%; however, in children, studies suggest the incidence may be lower One particular surgery in adolescents associated with a high incidence of persistent pain is scoliosis, where estimates of 50% are reported.84 A study by Wong demonstrated a trend for those who experienced more severe postoperative pain to have a greater tendency toward developing persistent pain; only 39% of those with mild postoperative pain developed persistent pain compared with 74% of those with severe postoperative pain Studies have indicated that persistent pain can be a complication for as long as 12 months after surgery; however, thoracotomy in childhood has been associated with pain persisting into adulthood up to 30 years later This risk appears less when surgery takes place at a younger age and increases with the age at which surgery is Hadzic_Ch45_p848-862.indd 859 performed Although the mechanisms for the transition from acute to chronic pain are complex, some risk factors identified in the adult literature (in the absence of many studies in children) may also be relevant to the pediatric population These include the presence of preoperative pain, the severity of acute postoperative pain, and open versus laparoscopic surgery Good postoperative multimodal pain management therefore plays an important role in efforts to prevent the subsequent development of persistent pain in children Chapter CHAPTER 45 X intravenous magnesium reduces opioid consumption, and to a lesser extent pain scores, in the first 24 hours postoperatively without any reported serious adverse effects.81 The use of magnesium, either as a bolus or infusion (at a dose of 30–50 mg/kg), for major surgeries, particularly spinal fusions, and for other major orthopedic and general surgeries, is standard practice at our institution 859 Clinical Pearls • Chronic pain can be a postoperative complication in the pediatric population • Chronic pain has a negative impact on sleep, activities, school attendance, and school achievement • Risks for the development of chronic pain include preoperative pain, the severity of acute postoperative pain, and open versus laparoscopic surgery THE MANAGEMENT OF ACUTE-ON-CHRONIC PAIN The management of patients undergoing surgery with preoperative chronic pain can be problematic, and the presence of preoperative pain increases pain perception postoperatively Good preoperative preparation and planning are important, incorporating education for both the child and parents/guardians and involving them in decision making Psychological interventions, such as cognitive behavioral therapy and decatastrophization can be beneficial preparation Patients experiencing preoperative pain may be taking adjuvant analgesia medications, some of which should not be stopped abruptly, such as anticonvulsants (eg, gabapentin) Other medications may have significant interactions with commonly used analgesic medications; for example, the combination of amitriptyline and tramadol has resulted in serotonin syndrome There are a small number of pediatric patients who present for surgery on long-term opioids, and not all of these patients will be palliative The prolonged administrations of opioids may occur in children in intensive care units, those requiring frequent and repeated surgery (eg, for burns), those with frequent disease exacerbations (eg, sickle cell), adolescents using opioids illicitly, and in a small number of children with medically unexplained pain Recommendations for the management of such patients are primarily extrapolated from the adult literature due to a lack of evidence in children (Table 45–5) SUMMARY The past 25 years have seen an explosion in research and interest in pediatric pain management In this brief review, we have tried to consolidate in a comprehensive manner some of the most commonly used agents and techniques in current practice 24/02/17 5:26 PM 860 PEDIATRIC ANESTHESIA TABLE 45–5. Considerations for the perioperative management of children on long-term opioids PART Educate and involve the child and his or her parents/ guardians in preoperative planning Continue maintenance opioids or consider conversion to parenteral opioids Supplementation with systemic opioid (oral or intravenous) may be necessary if a neuroaxial technique is used Titrate opioids postoperatively The dose may need to be 30%–100% higher than for opioid-naïve patients Use multimodal therapy, including adjuvant medications (eg, ketamine) and nonpharmacologic techniques Use regional anesthesia techniques where possible When transitioning from parenteral opioids to oral delivery calculate total dose requirement over 24 hours Deliver 50% of the estimated oral dose as long-acting and the remainder as breakthrough Taper oral opioids to preoperative doses slowly, over a period of 2-4 weeks In the first 24 postoperative hours, reduce the dose by 20–40% Following the first 24 postoperative hours, reduce the dose by 5–20% (use a slower rate in the presence of withdrawal signs) Ensure chronic pain service is involved in the transition to long-term pain management Source: Reproduced with permissions from Geary T, Negus A, Anderson BJ, et al: Perioperative management of the child on long-term opioids Paediatr Anaesth 2012 Mar;22(3):189-202 REFERENCES Schechter NL, Berde CB, Yaster M: Pain in Infants, Children, and Adolescents, 2nd ed Philadelphia: Lippincott Williams & Wilkins; 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Orthopedic surgeries suitable for epidural, combined spinal-epidural, or integrated epidural–general anesthesia PART. .. the level of the 23 / 02/ 17 4:33 PM 398 CLINICAL PRACTICE OF REGIONAL ANESTHESIA TABLE 24 –16. Anatomic landmarks to identify vertebral levels PART Vertebra prominens C7 Root of spine of scapula