Regional techniques and outcome: what is the evidence? Marie N. Hanna, Jamie D. Murphy, Kanupriya Kumar and Christopher L. Wu

Transcription

1 Regional techniques and outcome: what is the evidence? Marie N. Hanna, Jamie D. Murphy, Kanupriya Kumar and Christopher L. Wu Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, Maryland, USA Correspondence to Christopher L. Wu, MD, The Johns Hopkins Hospital, Carnegie 280, 600 North Wolfe Street, Baltimore, MD 21287, USA Tel: ; fax: ; Current Opinion in Anaesthesiology 2009, 22: Purpose of review Despite some controversy regarding the strength of the available data, the use of regional anesthesia and analgesia does provide improvement in patient outcomes. Although the majority of available data have examined the effect of epidural anesthesia and analgesia on patient outcomes, an increasing number of studies recently have investigated the effect of peripheral regional techniques on patient outcomes. Recent findings Data generally indicate that the perioperative use of regional anesthesia and analgesia may be associated with improvement in both major (e.g. mortality, major morbidity) outcomes and rehabilitation. The majority of evidence favors an ability of epidural analgesia to reduce postoperative cardiovascular and pulmonary complications and there is also consistent evidence that epidural analgesia with local anesthetics is associated with faster resolution of postoperative ileus after major abdominal surgery. Overall, regional analgesic techniques provide statistically superior analgesia compared with systemic opioids. Summary Perioperative use of regional analgesic techniques may provide improvement in conventional outcomes, although the benefit appears to be limited to high-risk patients and those undergoing high-risk procedures. The benefits conferred by perioperative regional anesthetic techniques need to be weighed against any potential risks and this should be assessed on an individual basis. Keywords epidural, outcomes, peripheral nerve block Curr Opin Anaesthesiol 22: ß 2009 Wolters Kluwer Health Lippincott Williams & Wilkins Introduction Perioperative use of regional anesthesia and analgesia may attenuate adverse perioperative pathophysiology and improve patient outcomes. Overall, the data suggest that the perioperative use of regional anesthesia and analgesia may improve both conventional (i.e. mortality and morbidity) and patient-centered outcomes. Although the majority of available data have examined the effect of epidural anesthesia and analgesia on patient outcomes, an increasing number of studies recently have investigated the effect of peripheral regional techniques on outcomes. We will review the recent data on the effect of perioperative regional anesthesia and analgesia on both conventional and patient-centered outcomes. Beneficial outcomes associated with regional anesthesia and analgesia Through the attenuation of perioperative pathophysiology and provision of superior analgesia, regional anesthesia analgesia may improve patient outcomes; however, the benefits of perioperative regional anesthesia analgesia are most apparent in patients with decreased physiologic reserves or who are undergoing higher risk procedures (e.g. thoracotomy). Mortality Prior meta-analyses and database analyses have examined the association of perioperative epidural anesthesia analgesia and patient mortality; however, the overall effect of epidural analgesia and patient mortality has been uncertain. The largest meta-analysis of randomized controlled trials (RCTs) comparing intraoperative neuraxial to general anesthesia (141 RCTs, 9559 patients) indicated a decrease in mortality [1.9 vs. 2.8%; odds ratio (OR) ¼ 0.7, 95% confidence interval (CI) ] [1]; however, other smaller, procedure-specific meta-analyses (e.g. open abdominal aortic surgery, coronary artery bypass grafting, hip and knee replacement surgery) have not shown any difference in mortality [2 5]. A 5% random sample of the Medicare claims database found that the presence of postoperative epidural analgesia was associated with a significantly lower incidence for both 7-day mortality ß 2009 Wolters Kluwer Health Lippincott Williams & Wilkins DOI: /ACO.0b013e32832f330a

2 Regional techniques and outcome Hanna et al. 673 (0.5 vs. 0.8%, OR ¼ 0.52, 95% CI ) and 30-day mortality (2.1 vs. 2.5%, OR ¼ 0.74, 95% CI ), with the benefit for decreased mortality apparent in patients undergoing higher risk procedures (e.g. lung resection, colectomy) but not in lower risk procedures (e.g. total knee replacement, hysterectomy) [6]. More recently, another database analysis also found that epidural anesthesia was associated with a reduction in 30- day mortality [1.7 vs. 2.0%; relative risk (RR) ¼ 0.89, 95% CI , P ¼ 0.02] [7 ]. The authors used a population-based linked administrative database to analyze a retrospective cohort study of patients (aged 40 years) who underwent elective intermediate-to-high risk noncardiac surgical procedures over a 10-year period. Although this most recent study does provide additional evidence that epidural analgesia may be associated with a decrease in perioperative mortality, these results should be interpreted cautiously as the overall evidence for reduction of mortality with epidural analgesia is inconsistent and there are methodologic issues with both metaanalysis and database analyses [6,8]. Cardiovascular At least three prior meta-analyses have indicated that the use of thoracic epidural anesthesia and analgesia (TEA) primarily utilizing a local anesthetic-based regimen may be associated with a reduction in perioperative cardiovascular events in high-risk patients or those undergoing high-risk procedures [1,3,9]. For instance, a meta-analysis examining RCTs in which epidural analgesia was used for a period of at least 24 h postoperatively, use of TEA (but not lumbar epidural analgesia) was associated with a significant reduction in the rate of myocardial infarction (OR ¼ 0.43, 95% CI , P ¼ 0.04) [9]. Use of TEA compared with systemic analgesia was associated with a significant reduction in risk of cardiovascular complications (RR ¼ 0.74, 95% CI ), myocardial infarction (RR ¼ 0.52, 95% CI ) (open abdominal aortic surgery) [2], and incidence of dysrhythmias (17.8 vs. 30%, OR ¼ 0.52, 95% CI ) (coronary artery bypass surgery) [3]. More recent studies continue to suggest a benefit for regional anesthesia and analgesia in reducing cardiovascular events, although whether there is greater hemodynamic stability is uncertain [10 ]. In patients undergoing off-pump coronary bypass graft surgery, patients who were randomized to receive a combined thoracic epidural general anesthesia regimen had a significant reduction in epinephrine serum levels and lower incidence of perioperative dysrhythmias (3 vs. 23.7% for general anesthesia only, P < 0.01) [11]. Although the mechanisms for these benefits are uncertain, recent data suggest that TEA may preserve cardiac/hemodynamic function and decrease arrhythmias after aortic cross clamp release through increased expression of vascular endothelial growth factor and inducible nitric oxide synthase [12]. Thus, there is consistent evidence that use of TEA may reduce the risk of cardiovascular morbidity in higher risk patients or those undergoing higher risk surgical procedures, although these benefits should be weighed against the risks of epidural hematoma on an individual basis [8,13]. Pulmonary Several older meta-analyses indicate that use of epidural anesthesia analgesia may significantly decrease the risk of perioperative pulmonary morbidity including postoperative pulmonary complications, pulmonary infections [3,14], and respiratory failure [2]. Some large RCTs also suggest some benefit for epidural analgesia in decreasing postoperative pulmonary complications with TEA [15,16]. These benefits may be related in part to the superior analgesia [17,18] provided by regional techniques, which may result in improved pulmonary function and decreased atelectasis, particularly in patients undergoing thoracic surgery [19,20]. More recent systematic reviews continue to indicate that the use of perioperative regional analgesia (including both epidural and paravertebral catheters) is associated with a decrease in pulmonary complications in patients undergoing abdominal and thoracic surgery. A metaanalysis examining the effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery noted that the odds of pneumonia were decreased with epidural analgesia (OR ¼ 0.54; 95% CI ), independent of site of surgery or catheter insertion, duration of analgesia, or regimen [21 ]. Although epidural analgesia reduced the need for prolonged ventilation or reintubation and improved lung function/blood oxygenation, it was also associated with an increased risk of hypotension, urinary retention, and pruritus [21 ]. Another systematic review noted that paravertebral analgesia was associated with a significant reduction in the incidence of pulmonary complications compared with systemic analgesia and continuous paravertebral block was as effective as TEA with local anesthetic but with a reduced incidence of hypotension [22 ]. Thus, meta-analyses and large RCTs suggest that use of TEA analgesia may decrease the risk of perioperative postoperative pulmonary complications; however, these benefits may be limited to patients with decreased physiologic reserves or those undergoing high-risk surgery such as abdominal aortic or thoracic surgery. Nevertheless, these benefits are not definitive, as quantitative meta-analyses are limited by heterogeneity in study design and the relative small sample size [22 ]. In

3 674 Regional anaesthesia addition, over the past 35 years, the incidence of pneumonia with epidural analgesia remained about 8% but has decreased from 34 to 12% with systemic analgesia, and, as a result, the relative benefit of epidural analgesia has diminished [21 ]. Gastrointestinal Prior data suggest that use of TEA with local anestheticbased solutions, compared with systemic and neuraxial opioids, is associated with faster recovery of bowel function after open abdominal surgery [23 25]. An earlier meta-analysis (22 RCTs, n ¼ 1023 patients) suggested that TEA with local anesthetics was associated with reduced time in return of gastrointestinal function (vs. systemic opioids 37 h, 95% CI 55 to 19 h; vs. epidural opioids 24 h, 95% CI 38 to 10 h) [23]. A subsequent meta-analysis noted that presence of epidural analgesia significantly reduced pain and duration of ileus but was associated with a significant increase in the incidence of pruritus, urinary retention, and hypotension [24]. More recent data also indicate that epidural analgesia is associated with reduced pain [26,27 ]. Unlike that seen for open abdominal procedures, the benefit of epidural analgesia in facilitating return of gastrointestinal function after laparoscopic procedures is equivocal [26,27 ]. Thus, the available meta-analyses suggest that TEA with local anesthetics (compared with both systemic and epidural opioids) facilitates return of postoperative gastrointestinal function after open abdominal surgery by h; however, the overall effect of TEA on gastrointestinal function after laparoscopic procedures and on other outcomes, such as length of stay, is unclear. The benefits of TEA are maximized when combined as part of a multimodal approach to postoperative rehabilitation (i.e. fasttrack surgery [28 ]). Rehabilitation Use of regional anesthesia analgesia may facilitate patient rehabilitation particularly after orthopedic procedures despite the potential for complications such as falls associated with peripheral nerve blocks [29]. Earlier RCTs have suggested that use of either continuous peripheral nerve catheters or epidural analgesia may improve early rehabilitation and decrease the time until readiness for discharge [30,31]. Recent studies confirm earlier findings in that use of continuous peripheral nerve analgesia can be used in an outpatient setting and results in decreases in the time to reach important predefined discharge criteria [32,33 ]. Compared with systemic opioids, regional analgesic techniques result in superior postoperative analgesia (vs. systemic opioids) and fewer opioid-related side effects [17,18,33,34,35,36], which may contribute to the earlier rehabilitation in these patients. Some other recent data also suggest that use of perioperative regional analgesic techniques may be associated with shorter hospital stays and reduction in overall costs, although additional studies are needed to confirm these findings [37,38,39]. Other outcomes Some data suggest that surgery induces suppression of antimetastatic cell-mediated immunity (CMI) at this critical period, which is suggested to worsen patients prognosis [40]. It is clear that perioperative regional anesthesia analgesia may attenuate adverse metabolic, inflammatory, and immunologic responses [41,42,43, 44 ] such that regional anesthesia analgesia may diminish perioperative immunosuppression [45,46 ]. Theoretically, patients undergoing cancer surgery might benefit from attenuation of perioperative immunosuppression (i.e. longer survival) by regional anesthesia analgesia. Two retrospective analyses suggest that use of perioperative regional anesthesia analgesia is associated with a lower risk of recurrence/metastasis and substantially less risk of biochemical cancer recurrence [47,48]. Risks associated with regional anesthesia and analgesia Despite the benefits associated with using perioperative regional anesthesia analgesia, the potential risks from each regional technique should be considered on an individual basis. Although a comprehensive review of risks from regional analgesic techniques are beyond the scope of this review, the recent controversial topics regarding complications and safety with regional techniques will be discussed. Neurologic complications of regional techniques Both neuraxial and peripheral regional techniques may be associated with perioperative neurologic injury [49,50,51 ]. Although the mechanisms of neurologic injury are often unclear or multifactoral, nerve injury may occur when local anesthetics are injected intrafascicularly into peripheral nerves (particularly if the concentration is high or duration of exposure is prolonged), needle penetration of a nerve is combined with local anesthetic administration within the nerve fascicle, or there is direct compression by a pronged tourniquet application [52]. Despite the wide range of risks that may occur from regional techniques, the risks of regional anesthesia most commonly disclosed to patients are benign in nature and occur frequently, whereas severe complications associated with these techniques are far less commonly disclosed [53]. In addition, recent data

4 Regional techniques and outcome Hanna et al. 675 suggest that there is little agreement among regional anesthesiologists regarding their perceived incidence of complications following regional techniques [54]. There are recent societal practice advisories on neurologic complications in regional anesthesia and pain medicine which include an evidence-based and expert opinion-based section on performing procedures on anesthetized or heavily sedated patients [55,56]. Finally, the clinician should be aware of the early treatment with 10% intravenous fat emulsion (i.e. Intralipid), which may help prevent cardiac arrest and speed successful resuscitation efforts due to local anesthetic toxicity [57 ]. Improvement of safety of regional techniques with use of ultrasound? The utilization of ultrasound to guide needle placement and monitor the injection of local anesthetics has been associated with an improvement in the success rate of various peripheral nerve blocks [58,59 ]. In addition, ultrasound has been used to facilitate neuraxial blocks particularly in neonates and children [60,61]. Ultrasound-guided nerve blocks may result in not only higher success but also in faster onset and progression of sensorimotor block without an increase in block procedure time [62 ]. One of the important and unanswered questions regarding the use of ultrasound to guide nerve blocks is whether this technique will actually result in a lower incidence or severity of neurologic complications compared with other currently used techniques such as nerve stimulation [63]. As with any newer technique, there will be a learning curve when introducing ultrasound into a clinician s practice and as such clinicians will need to be familiar with the anatomical landmarks for their blocks and be cognizant of the potential artifacts and pitfall errors associated with ultrasound-guided regional anesthesia [64 67]. Conclusion The use of regional anesthesia and analgesia may improve perioperative patient outcomes. Although the use of perioperative epidural anesthesia and analgesia may improve cardiac, pulmonary, and gastrointestinal outcomes, any benefits are limited to higher risk patient and higher risk procedures. Use of continuous peripheral regional analgesia may be associated with improvement in patient rehabilitation. Although use of ultrasound may be associated with an increase in success rate, whether this technique may be associated with a decreased rate of neurologic injury is uncertain. Future research should be directed at emerging technologies [68 ] and the effect of regional analgesic techniques on patient-reported outcomes [69,70]. Acknowledgement The present study was supported by the Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD, USA. References and recommended reading Papers of particular interest, published within the annual period of review, have been highlighted as: of special interest of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (pp ). 1 Rodgers A, Walker N, Schug S, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. BMJ 2000; 321: Nishimori M, Ballantyne JC, Low JH. Epidural pain relief versus systemic opioid based pain relief for abdominal aortic surgery. Cochrane Database Syst 2006:CD Liu SS, Block BM, Wu CL. Effects of perioperative central neuraxial analgesia on outcome after coronary artery bypass surgery: a meta-analysis. Anesthesiology 2004; 101: Werawatganon T, Charuluxanun S. Patient controlled intravenous opioid analgesia versus continuous epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev 2005:CD Choi PT, Bhandari M, Scott J, et al. Epidural analgesia for pain relief following hip or knee replacement. Cochrane Database Syst Rev 2003:CD Wu CL, Hurley RW, Anderson GF, et al. Effect of postoperative epidural analgesia on morbidity and mortality following surgery in Medicare patients. Reg Anesth Pain Med 2004; 29: Wijeysundera DN, Beattie WS, Austin PC, et al. Epidural anaesthesia and survival after intermediate-to-high risk noncardiac surgery: a population-based cohort study. Lancet 2008; 372: The results suggest that perioperative epidural anesthesia analgesia is associated with an improvement in 30-day survival and support the safety of perioperative epidural anesthesia. 8 Liu SS, Wu CL. Effect of postoperative analgesia on major postoperative complications: a systematic update of the evidence. Anesth Analg 2007; 104: Beattie WS, Badner NH, Choi P. Epidural analgesia reduces postoperative myocardial infarction: a meta-analysis. Anesth Analg 2001; 93: Luchetti M, Canella M, Zoppi M, et al. Comparison of regional anesthesia versus combined regional and general anesthesia for elective carotid endarterectomy: a small exploratory study. Reg Anesth Pain Med 2008; 33: This study suggests that combined regional/general anesthesia provides greater hemodynamic stability and patient comfort compared with regional anesthesia during carotid endarterectomy. 11 Bakhtiary F, Therapidis P, Dzemali O, et al. Impact of high thoracic epidural anesthesia on incidence of perioperative atrial fibrillation in off-pump coronary bypass grafting: a prospective randomized study. J Thorac Cardiovasc Surg 2007; 134: Gonca S, Kiliçkan L, Dalçik C, et al. The cardioprotective effects of thoracal epidural anesthesia are induced by the expression of vascular endothelial growth factor and inducible nitric oxide synthase in cardiopulmonary bypass surgery. J Cardiovasc Surg 2007; 48: Bergqvist D, Wu CL, Neal JM. Anticoagulation and neuraxial regional anesthesia: perspectives. Reg Anesth Pain Med 2003; 28: Ballantyne JC, Carr DB, deferranti S, et al. The comparative effects of postoperative analgesictherapiesonpulmonaryoutcome: cumulativemeta-analyses of randomized, controlled trials. Anesth Analg 1998; 86: Park WY, Thompson JS, Lee KK. Effect of epidural anesthesia and analgesia on perioperative outcome: a randomized, controlled Veterans Affairs cooperative study. Ann Surg 2001; 234: Rigg JR, Jamrozik K, Myles PS, et al. Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet 2002; 359: Block BM, Liu SS, Rowlingson AJ, et al. Efficacy of postoperative epidural analgesia: a meta-analysis. JAMA 2003; 290: Wu CL, Cohen SR, Richman JM, et al. Efficacy of postoperative patientcontrolled and continuous infusion epidural analgesia versus intravenous patient-controlled analgesia with opioids: a meta-analysis. Anesthesiology 2005; 103:

5 676 Regional anaesthesia 19 Tenenbein PK, Debrouwere R, Maguire D, et al. Thoracic epidural analgesia improves pulmonary function in patients undergoing cardiac surgery. Can J Anaesth 2008; 55: The results of this study suggest that thoracic epidural analgesia is associated with decreased postoperative pain and atelectasis and improvement in pulmonary function in patients undergoing coronary artery bypass surgery. 20 Behera BK, Puri GD, Ghai B. Patient-controlled epidural analgesia with fentanyl and bupivacaine provides better analgesia than intravenous morphine patient-controlled analgesia for early thoracotomy pain. J Postgrad Med 2008; 54: Pöpping DM, Elia N, Marret E, et al. Protective effects of epidural analgesia on pulmonary complications after abdominal and thoracic surgery: a meta-analysis. Arch Surg 2008; 143: This meta-analysis suggests that perioperative epidural analgesia may reduce the need for prolonged ventilation or reintubation, improve lung function and blood oxygenation, but may increase the risk of hypotension, urinary retention, and pruritus. The data corroborate earlier meta-analyses on this topic. 22 Joshi GP, Bonnet F, Shah R, et al. A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia. Anesth Analg 2008; 107: This systematic review indicates that paravertebral block reduces the incidence of pulmonary complications compared with systemic analgesia and either thoracic epidural analgesia with local anesthetics plus opioid or continuous paravertebral block with local anesthetics can be recommended. This review is slightly different from prior reviews in that it examines the data for only one procedure. 23 Jorgensen H, Wetterslev J, Moiniche S, et al. Epidural local anaesthetics versus opioid-based analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane Database Syst Rev 2000:CD Marret E, Remy C, Bonnet F, et al. Meta-analysis of epidural analgesia versus parenteral opioid analgesia after colorectal surgery. Br J Surg 2007; 94: Steinberg RB, Liu SS, Wu CL, et al. Comparison of ropivacaine-fentanyl patient-controlled epidural analgesia with morphine intravenous patient-controlled analgesia for perioperative analgesia and recovery after open colon surgery. J Clin Anesth 2002; 14: Zingg U, Miskovic D, Hamel CT, et al. Influence of thoracic epidural analgesia on postoperative pain relief and ileus after laparoscopic colorectal resection: benefit with epidural analgesia. Surg Endosc 2009; 23: Turunen P, Carpelan-Holmström M, Kairaluoma P, et al. Epidural analgesia diminished pain but did not otherwise improve enhanced recovery after laparoscopic sigmoidectomy: a prospective randomized study. Surg Endosc 2009; 23: This study suggests that epidural analgesia would be useful even for lapaoscopic procedures as this technique significantly decreases pain and opioids intake during the first 48 h after laparoscopic sigmoidectomy. 28 Kehlet H. Postoperative ileus: an update on preventive techniques. Nat Clin Pract Gastroenterol Hepatol 2008; 5: This article reviews techniques currently used to prevent or reduce the duration of postoperative ileus. With current techniques, the duration of postoperative ileus after open or laparoscopic abdominal surgery can be reduced to h for most patients; however, additional data on the effect of these techniques when applied to major upper abdominal surgeries and emergency abdominal operations are needed. 29 Muraskin SI, Conrad B, Zheng N, et al. Falls associated with lower-extremitynerve blocks: a pilot investigation of mechanisms. Reg Anesth Pain Med 2007; 32: Capdevila X, Barthelet Y, Biboulet P, et al. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery. Anesthesiology 1999; 91: Ilfeld BM, Vandenborne K, Duncan PW, et al. Ambulatory continuous interscalene nerve blocks decrease the time to discharge readiness after total shoulder arthroplasty: a randomized, triple-masked, placebo-controlled study. Anesthesiology 2006; 105: Ilfeld BM, Le LT, Meyer RS, et al. Ambulatory continuous femoral nerve blocks decrease time to discharge readiness after tricompartment total knee arthroplasty: a randomized, triple-masked, placebo-controlled study. Anesthesiology 2008; 108: Compared with an overnight continuous femoral nerve block, a 4-day ambulatory continuous femoral nerve block decreased the time to reach three important discharge criteria by approximately 53% after tricompartment total knee arthroplasty. This study provides additional evidence that an continuous regional analgesia may improve rehabilitation after orthopedic surgery. 33 Ilfeld BM, Ball ST, Gearen PF, et al. Ambulatory continuous posterior lumbar plexus nerve blocks after hip arthroplasty: a dual-center, randomized, triplemasked, placebo-controlled trial. Anesthesiology 2008; 109: Compared with an overnight continuous lumbar plexus block, a 4-day ambulatory continuous lumbar plexus block decreases the time to reach three predefined discharge criteria by approximately 38% after hip arthroplasty. This study provides additional evidence that continuous regional analgesia may improve rehabilitation after orthopedic surgery. 34 Fowler SJ, Symons J, Sabato S, et al. Epidural analgesia compared with peripheral nerve blockade after major knee surgery: a systematic review and meta-analysis of randomized trials. Br J Anaesth 2008; 100: This meta-analysis suggests that peripheral nerve blocks provide comparable levels of analgesia to epidural analgesia for major knee surgery; however, hypotension occurred more frequently in patients who received epidurals. 35 Siddiqui ZI, Cepeda MS, Denman W, et al. Continuous lumbar plexus block provides improved analgesia with fewer side effects compared with systemic opioids after hip arthroplasty: a randomized controlled trial. Reg Anesth Pain Med 2007; 32: Richman JM, Liu SS, Courpas G, et al. Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis. Anesth Analg 2006; 102: Ludot H, Berger J, Pichenot V, et al. Continuous peripheral nerve block for postoperative pain control at home: a prospective feasibility study in children. Reg Anesth Pain Med 2008; 33: This study demonstrates that ambulatory continuous peripheral analgesia may be used for children and decrease hospital stays (although with appropriate patient selection and parental supervision). 38 Ilfeld BM, Mariano ER, Williams BA, et al. Hospitalization costs of total knee arthroplasty with a continuous femoral nerve block provided only in the hospital versus on an ambulatory basis: a retrospective, case-control, costminimization analysis. Reg Anesth Pain Med 2007; 32: Bracco D, Noiseux N, Dubois MJ, et al. Epidural anesthesia improves outcome and resource use in cardiac surgery: a single-center study of a 1293-patient cohort. Heart Surg Forum 2007; 10:E449 E Goldfarb Y, Ben-Eliyahu S. Surgery as a risk factor for breast cancer recurrence and metastasis: mediating mechanisms and clinical prophylactic approaches. Breast Dis 2007; 26: Lugli AK, Donatelli F, Schricker T, et al. Epidural analgesia enhances the postoperative anabolic effect of amino acids in diabetes mellitus type 2 patients undergoing colon surgery. Anesthesiology 2008; 108: Lattermann R, Wykes L, Eberhart L, et al. A randomized controlled trial of the anticatabolic effect of epidural analgesia and hypocaloric glucose. Reg Anesth Pain Med 2007; 32: Bagry H, de la Cuadra Fontaine JC, Asenjo JF, et al. Effect of a continuous peripheral nerve block on the inflammatory response in knee arthroplasty. Reg Anesth Pain Med 2008; 33: This study provides evidence that continuous peripheral analgesia with local anesthetics may be associated with an attenuation of the postoperative inflammatory response. 44 Martin F, Martinez V, Mazoit JX, et al. Antiinflammatory effect of peripheral nerve blocks after knee surgery: clinical and biologic evaluation. Anesthesiology 2008; 109: The authors indicate that peripheral nerve blocks may inhibit clinical inflammation after total knee arthroplasty. 45 Hong JY, Lim KT. Effect of preemptive epidural analgesia on cytokine response and postoperative pain in laparoscopic radical hysterectomy for cervical cancer. Reg Anesth Pain Med 2008; 33: Ahlers O, Nachtigall I, Lenze J, et al. Intraoperative thoracic epidural anaesthesia attenuates stress-induced immunosuppression in patients undergoing major abdominal surgery. Br J Anaesth 2008; 101: This study provides additional evidence that an intraoperative thoracic epidural catheter with local anesthetic may attenuate the stress response and prevent stress-induced perioperative impairment of proinflammatory lymphocyte function. 47 Biki B, Mascha E, Moriarty DC, et al. Anesthetic technique for radical prostatectomy surgery affects cancer recurrence: a retrospective analysis. Anesthesiology 2008; 109: Compared with general anesthesia opioid analgesia, regional anesthesia analgesia was associated with a significantly less risk of biochemical cancer recurrence. This is one of the few clinical studies to suggest that attenuation of perioperative immunosuppression may result in improvement of cancer survival rates. 48 Exadaktylos AK, Buggy DJ, Moriarty DC, et al. Can anesthetic technique for primary breast cancer surgery affect recurrence or metastasis? Anesthesiology 2006; 105: Sorenson EJ. Neurological injuries associated with regional anesthesia. Reg Anesth Pain Med 2008; 33:

6 Regional techniques and outcome Hanna et al Neal JM. Anatomy and pathophysiology of spinal cord injury associated with regional anesthesia and pain medicine. Reg Anesth Pain Med 2008; 33: Lee LA, Posner KL, Cheney FW, et al. Complications associated with eye blocks and peripheral nerve blocks: an American Society of Anesthesiologists closed claims analysis. Reg Anesth Pain Med 2008; 33: This closed claims analysis suggests that the performance of eye blocks by anesthesiologists significantly increases the liability profile, primarily related to permanent eye damage from block needle trauma. The analysis also indicates that although most peripheral nerve block claims are associated with temporary injuries, local anesthetic toxicity is a major cause of death or brain damage in these claims. 52 Hogan QH. Pathophysiology of peripheral nerve injury during regional anesthesia. Reg Anesth Pain Med 2008; 33: Brull R, McCartney CJ, Chan VW, et al. Disclosure of risks associated with regional anesthesia: a survey of academic regional anesthesiologists. Reg Anesth Pain Med 2007; 32: Brull R, Wijayatilake DS, Perlas A, et al. Practice patterns related to block selection, nerve localization and risk disclosure: a survey of the American Society of Regional Anesthesia and Pain Medicine. Reg Anesth Pain Med 2008; 33: Neal JM, Bernards CM, Hadzic A, et al. ASRA Practice Advisory on Neurologic Complications in Regional Anesthesia and Pain Medicine. Reg Anesth Pain Med 2008; 33: This is one of the few available practice advisories on this topic and addresses the cause, differential diagnosis, prevention, and treatment of these complications. The practice advisory provides recommendations in attempt in part to potentially limit neurologic complications that may occur during the practice of regional anesthesia and pain medicine. 56 BernardsCM,HadzicA,SureshS,et al. Regional anesthesia in anesthetized or heavily sedated patients. Reg Anesth Pain Med 2008; 33: McCutchen T, Gerancher JC. Early intralipid therapy may have prevented bupivacaine-associated cardiac arrest. Reg Anesth Pain Med 2008; 33: Intralipid has become widely recognized as a treatment option for local anestheticinduced cardiac arrest. The authors suggest that early (rather than later) treatment with Intralipid may help prevent cardiac arrest and facilitate successful resuscitation efforts. 58 Kapral S, Greher M, Huber G, et al. Ultrasonographic guidance improves the success rate of interscalene brachial plexus blockade. Reg Anesth Pain Med 2008; 33: This study indicates that the use of ultrasound to guide needle placement and monitor the spread of local anesthetic may improve the success rate of interscalene brachial plexus block. 59 Macaire P, Singelyn F, Narchi P, et al. Ultrasound- or nerve stimulation-guided wrist blocks for carpal tunnel release: a randomized prospective comparative study. Reg Anesth Pain Med 2008; 33: This study suggests that ultrasound-guided wrist nerve blocks are as efficient as those performed with nerve stimulation. 60 Kil HK, Cho JE, Kim WO, et al. Prepuncture ultrasound-measured distance: an accurate reflection of epidural depth in infants and small children. Reg Anesth Pain Med 2007; 32: Willschke H, Bosenberg A, Marhofer P, et al. Epidural catheter placement in neonates: sonoanatomy and feasibility of ultrasonographic guidance in term and preterm neonates. Reg Anesth Pain Med 2007; 32: Perlas A, Brull R, Chan VW, et al. Ultrasound guidance improves the success of sciatic nerve block at the popliteal fossa. Reg Anesth Pain Med 2008; 33: The authors demonstrate that ultrasound guidance enhances the quality of popliteal sciatic nerve block compared with single injection, nerve stimulatorguided block. 63 Fredrickson MJ. The sensitivity of motor response to needle nerve stimulation during ultrasound guided interscalene catheter placement. Reg Anesth Pain Med 2008; 33: Sites BD, Spence BC, Gallagher JD, et al. Characterizing novice behavior associated with learning ultrasound-guided peripheral regional anesthesia. Reg Anesth Pain Med 2007; 32: Sites BD, Brull R, Chan VW, et al. Artifacts and pitfall errors associated with ultrasound-guided regional anesthesia. Part I: Understanding the basic principles of ultrasound physics and machine operations. Reg Anesth Pain Med 2007; 32: Sites BD, Brull R, Chan VW, et al. Artifacts and pitfall errors associated with ultrasound-guided regional anesthesia. Part II: A pictorial approach to understanding and avoidance. Reg Anesth Pain Med 2007; 32: Ajar A, Hoeft M, Alsofrom GF, et al. Review of brachial plexus anatomy as seen on diagnostic imaging: clinical correlation with computed tomography-guided brachial plexus block. Reg Anesth Pain Med 2007; 32: Viscusi ER. Patient-controlled drug delivery for acute postoperative pain management: a review of current and emerging technologies. Reg Anesth Pain Med 2008; 33: The author provides an update on the benefits and drawbacks of both existing and emerging patient-controlled analgesia modalities and provides a critical evaluation of their use in postoperative settings. 69 Wu CL, Rowlingson AJ, Partin AW, et al. Correlation of postoperative pain to quality of recovery in the immediate postoperative period. Reg Anesth Pain Med 2005; 30: Liu SS, Wu CL. The effect of analgesic technique on postoperative patientreported outcomes including analgesia: a systematic review. Anesth Analg 2007; 105: