C HAPTER 19
V O L U M E T H I R T Y -F I V
E A CUTE P AIN M ANAGEMENT :
D OES I T A LTER
P ERIOPERATIVE O UTCOME ?
C HRISTOPHER L. W U , M.D.
A SSOCIATE P ROFESSOR
D EPARTMENT OF A NESTHESIOLOGY AND C RITICAL C AR
E M EDICINE
T HE J OHNS H OPKINS U NIVERSITY
B ALTIMORE , M ARYLAND
The American Society of Anesthesiologists, Inc.E DITOR :A LAN J AY S CHWARTZ , M.D., M.S. E D .
A SSOCIATE E DITORS :J OHN F.
B UTTERWORTH IV, M.D.
J EFFREY B. G ROSS , M.D.
?2007
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Acute Pain Management: Does It Alter
Perioperative Outcome?
Christopher L. Wu, M.D.
Associate Professor
Department of Anesthesiology and Critical Care Medicine
The Johns Hopkins University
Baltimore, Maryland
There has been an increasing awareness of the importance of acute pain manage-ment, particularly with multiple studies revealing the frequent undertreatment of acute pain. There have been attempts to establish pain management standards. There are many options (e.g.,techniques, drugs) for the treatment of acute postoperative pain and it is possible that acute pain management may in?uence perioperative outcomes.
Perioperative Pathophysiology
The systemic response to surgical incision may contribute to perioperative morbidity and mortality. There are several systematic responses to surgery, including sympathetic nervous system activation, the neuroendocrine stress response, and inflammatory–immunologic changes (Table 1). These may result in a number of adverse responses within many organ systems, such as an increase in heart rate and blood pressure, decrease in gastrointestinal (GI) motility, and decrease in pulmonary functional residual capacity/ vital capacity. Through afferent neural stimuli, activation of the autonomic nervous sys-tem and of spinal re?exes, pain per se may be an important trigger of the surgical stress response.1In addition, acute postoperative pain may contribute to peripheral and central sensitization and the development of chronic pain syndromes. Attenuation of adverse responses to surgical incision might lead to improved perioperative outcomes, particularly in patients with decreased physiological reserve. Analgesic agents differ in their ability to attenuate the adverse pathophysiological responses to surgery. For instance, analgesic agents differ in their ability to attenuate the stress response, attenu-ate adverse spinal re?exes, and to provide analgesia. Because different analgesic agents may confer different physiological bene?ts, it is possible that there may be differences in outcomes with use of different analgesic regimens.
Outcomes
In studying the effects of acute pain management on perioperative outcomes, we have traditionally focused on the outcomes of mortality and major morbidity, including cardiovascular (e.g.,myocardial infarction), pulmonary (e.g.,pneumonia, atelectasis), and GI (e.g.,recovery of bowel function) end points. More recently, patient-oriented (“nontraditional”) end points such as patient satisfaction, health-related quality of life, and quality of recovery have become more prominent (Table 2).
Copyright ?2007 American Society of Anesthesiologists, Inc.227
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T ABLE1.Perioperative Pathophysiology
Systematic responses to surgery
Sympathetic nervous system activation
Neuroendocrine stress response
Immunologic–in?ammatory changes
Physiological disturbances
Cardiovascular: increased heart rate, blood pressure
Gastrointestinal: ileus
Pulmonary: decreased lung volumes
Renal: decreased renal blood ?ow
Mortality
The overall bene?ts of perioperative acute pain management on mortality remain controversial, attributed in part to methodological and study design issues present in smaller underpowered clinical trials. The results of several randomized, controlled tri-als (RCTs)2,3and recent meta-analyses,4–7showing no difference in mortality with use of epidural analgesia, are at odds with the largest available meta-analysis of 141 RCTs8 that showed a reduction in mortality with perioperative use of neuraxial anesthesia and analgesia. Despite the uncertainty of the effect of acute pain management on peri-operative mortality, there are some data suggesting that the presence of postoperative epidural analgesia may be associated with a lower risk of death for certain procedures.9 A 5% random sample of the Medicare claims database examined patients under-going a variety of surgical procedures and stratified them according to the presence (n =12,780 subjects) or absence (n =55,943) of a bill for postoperative epidural anal-gesia.Regression analysis revealed that presence of postoperative epidural analgesia was associated with a signi?cantly reduced odds ratio for both 7- and 30-day mortal-ity.9When examining mortality by speci?c procedures, the bene?t in lower mortality for epidural analgesia was only seen in patients who underwent higher-risk procedures (e.g.,lung resection, colectomy) but not lower-risk procedures (e.g.,total knee replace-ment, hysterectomy).
Major Morbidity
The systemic neuroendocrine and in?ammatory response to injury that follows surgery affects all organ systems; however, not all patients will develop postoperative complications. It is well recognized that certain subgroups (e.g.,older patients, those
T ABLE2.Types of Outcomes
“Traditional” outcomes
Mortality
Major morbidity (cardiovascular, gastrointestinal, pulmonary)
“Nontraditional” or patient-oriented outcomes
Analgesia
Quality of life
Quality of recovery
Satisfaction
ACUTE PAIN MANAGEMENT229 T ABLE3.Effect of Epidural Analgesia on Major Morbidity Cardiovascular: decreased myocardial infarction, dysrhythmias
Coagulation: no difference
Gastrointestinal: decreased ileus
Pulmonary: decreased pulmonary complications
with decreased physiological reserve, procedure-speci?c [lung resection, coronary artery bypass]) may be at higher risk for developing postoperative complications. The differing physiological and analgesic bene?ts of different analgesic agents and tech-niques may result in differences in perioperative morbidity (Table 3).
Pulmonary
Postoperative pulmonary complications (PPCs) affect approximately 10% of patients undergoing elective abdominal surgery.10The pathophysiology of PPCs is multifactorial and includes disruption of normal respiratory muscle activity (either from surgery or anesthesia), re?ex inhibition of diaphragmatic function, and pain, which may cause voluntary inhibition of respiratory activity.10All of these factors may contribute to a decrease in lung volumes, which in turn may contribute to the development of atelec-tasis and PPC.
There are four meta-analyses (three epidural, one intravenous patient-controlled analgesia [PCA] opioids), which suggest that intensive postoperative pain management may reduce the likelihood of PPC.4,7,11A meta-analysis of 48 RCTs found that the use of epidural analgesia with local anesthetic (but not epidural opioids, intercostals block, or intrapleural analgesia) was associated with a signi?cant decrease in the relative risk of developing PPC.11Another meta-analysis examining patients undergoing coronary artery bypass found that the perioperative use of thoracic epidural analgesia (TEA) was associated with a signi?cantly decreased risk of PPC.7Another meta-analysis examined patients undergoing open abdominal aortic surgery and noted that epidural analgesia decreased the risk of respiratory failure.4Finally, one systematic review suggested that intravenous PCA with opioids (versus as-needed systemic opioids) was associated with a slight but statistically signi?cant decrease in PPCs12; however, two other meta-analyses comparing intravenous PCA to as-needed opioids did not ?nd any decrease in PPCs with intravenous PCA13,14and as such, the clinical meaningfulness of these data is uncertain. One of the methodological issues in examining the effect of postoperative pain management on PPCs is that there are widely varying de?nitions of what actually constitutes a “PPC.”
Cardiovascular
Approximately 5% of the worldwide surgical population (approximately 5 million annually) will develop some type of perioperative cardiac morbidity.15Traditionally, it is thought that an imbalance of myocardial oxygen supply and demand (increase in demand from increase in heart rate or blood pressure or decrease in supply particu-larly to the subendocardial areas) may contribute to perioperative cardiac morbidity. Although individual RCTs might seem equivocal on whether postoperative pain man-agement affects perioperative cardiac outcomes, three meta-analyses suggest that TEA (but not consistently lumbar epidural analgesia) might be associated with an improve-ment in perioperative cardiac outcomes.4,7,16The ?rst meta-analysis noted that TEA but not lumbar epidural analgesia was associated with a signi?cant decrease in the risk of
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postoperative myocardial infarction.16The second meta-analysis in patients undergoing coronary artery bypass found a signi?cant decrease in the risk of dysrhythmias with TEA.7 The last meta-analysis examined patients undergoing open abdominal aortic surgery and noted that epidural analgesia decreased the risk of overall cardiovascular complications and myocardial infarction.4The fact that TEA consistently is associated with a decrease in perioperative cardiac events is consistent with experimental data demonstrating a bene?t with TEA.
Gastrointestinal
The pathophysiology of decreased GI motility and postoperative ileus is multi-factorial and includes neurogenic (spinal, supraspinal adrenergic pathways), in?am-matory (i.e.,local in?ammatory responses initiate neurogenic inhibitory pathways), and pharmacologic (e.g.,opioids) mechanisms.17Analgesic agents differ in their effects on GI motility and as such, it is reasonable to expect a difference in rate of return of GI func-tion with different analgesic regimens. A systematic review from the Cochrane database indicated that when compared with either systemic or epidural opioids, epidural analgesia using a local anesthetic-based regimen will provide an earlier postoperative return of GI function.18Furthermore, the proper placement of the epidural catheter (i.e.,“catheter-incision congruent analgesia”: catheter insertion site is congruent to the incisional dermatome) may in?uence the ef?cacy of epidural analgesia with regard to return of GI function.19When limiting the comparison to epidural regimens using a local anesthetic-based regimen, a catheter-incision congruent analgesia (i.e.,TEA for abdom-inal surgery) technique provides earlier return of GI function than a catheter-incision in congruent analgesia technique.19Finally, a meta-analysis suggests that the addition, of nonsteroidal antiin?ammatory drugs had no impact on bowel dysfunction despite reduced opioid use with nonsteroidal antiin?ammatory drugs.20
Coagulation
Perioperative coagulation-related complications may be an important cause of mor-bidity. In the absence of thromboembolic prophylaxis, the incidence of fatal pulmonary embolism ranges from 0.1% to 0.8% after general surgery, 0.3% to 1.7% after elective hip surgery, and 4% to 7% after emergency hip surgery.21The pathophysiology of coagulation-related events (e.g.,deep venous thrombosis) has essentially been unchanged since Virchow’s initial description of his triad of stasis, blood vessel injury, and hyper-coagulability.21It is widely recognized that hypercoagulability occurs with surgical incision.
We also recognize that intra operative neuraxial anesthesia may attenuate peri-operative hypercoagulability and increase extremity blood ?ow, both of which may contribute to a decrease in perioperative coagulation-related complications. A meta-analysis of RCTs indicated that use of intraoperative neuraxial anesthesia was associated with a decrease in odds of developing deep vein thrombosis by 44% and pulmonary embolism by 55%.8Nevertheless, it is unclear if post operative epidural analgesia might continue the physiological bene?ts conferred by intraoperative neuraxial anesthesia and contribute to a decrease in perioperative coagulation-related complications. Some of the available data suggest that postoperative epidural analgesia using common local analgesic concentrations (≤0.125% bupivacaine) does not provide the physiological bene?ts seen with intraoperative neuraxial anesthesia. Postoperative epidural analgesia does not appear to provide any signi?cant increase in whole limb, venous, or cutaneous blood ?ow nor a decrease in postoperative hypercoagulability.22,23Further complicat-ing the issue of whether postoperative epidural analgesia might in?uence the incidence
ACUTE PAIN MANAGEMENT231 of perioperative coagulation-related complications is the fact that few studies in this area have used concurrent prophylactic anticoagulation.
Epidural Analgesia Is Not a Generic Intervention
A methodological issue in some trials evaluating the ef?cacy of epidural analgesia in decreasing morbidity or mortality is that the effect of postoperative epidural analgesia is dependent in part on the speci?c management of this technique. Speci?c factors in epidural management that might in?uence outcomes include: (1) the type of analgesic regimen (i.e.,opioids may provide analgesia but do not have the physiological bene-?ts of local anesthetics), (2) congruency of catheter tip to surgical incision dermatome, (3) duration of epidural analgesia (i.e.,premature removal may negate any potential physiological or analgesic bene?ts), and (4)whether epidural analgesia is used as part of a multimodal technique. Any one or all of these factors might in?uence outcomes.
“Nontraditional”/Patient-Oriented End Points There has been an increasing interest in using patient-oriented outcomes in assessment of the ef?cacy of different postoperative analgesic regimens. These “nontraditional”outcomes include end points such as patient satisfaction, quality of life, and quality of recovery, all of which are important and valid outcomes. Despite the uncommon use of these end points in anesthesiology trials, such patient-oriented end points have been widely used in other areas of medicine and may become more important in light of the decreasing incidence of anesthetic-related morbidity and mortality. There are many aspects of perioperative care (e.g.,degree of analgesia, presence of side effects) that might affect patient-oriented outcomes.
Analgesia
Different analgesic regimens provide different qualities of postoperative analgesia (Table 4). In general, postoperative regional analgesic techniques (e.g.,continuous epidural and peripheral catheter) provide superior analgesia compared with systemic opioid techniques.24–26A meta-analysis of RCTs indicates that continuous epidural analgesia provides superior analgesia versus patient-controlled epidural analgesia, although at a cost of increased side effects (e.g.,motor block).24Intravenous PCA opioids in general appear to provide superior analgesia compared with as-needed sys-temic opioids.12–14The side effect pro?le (which may also be an important in?uence on patient-oriented outcomes) may differ among analgesic techniques. Patient-controlled epidural analgesia is associated with a lower incidence of postoperative nausea or T ABLE4.Postoperative Analgesia Among Various Techniques
Epidural analgesia provides superior postoperative analgesia versus:
Parenteral opioids
Intravenous patient-controlled analgesia with opioids
Continuous peripheral analgesia provides superior postoperative analgesia versus:
Systemic opioids
Continuous epidural infusions provides superior postoperative analgesia versus:
Patient-controlled epidural analgesia
Epidural analgesia with a local anesthetic-based solution provides superior postoperative analgesia versus:
Epidural analgesia with opioids
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vomiting and sedation but carries a greater risk of pruritus or motor block.25Continu-ous peripheral (local anesthetic) analgesia is associated with a lower incidence of postoperative nausea or vomiting, sedation, and pruritus but a higher incidence of motor block.26
Quality of Life, Quality of Recovery, Satisfaction
Health-related quality of life, quality of recovery, and satisfaction are related con-ceptually and can be assessed using validated survey instruments. The timeframe for assessment of Health-related quality of life is typically months, not days like quality of recovery. Factors other than degree of analgesia and presence of analgesic agent-related side effects (e.g.,fatigue, physical functioning, mental health) may potentially in?uence Health-related quality of life or quality of life. There are few studies examining the effect of postoperative analgesic regimens on these outcomes. An RCT in patients undergoing colectomy compared intravenous PCA opioid with epidural analgesia. Patients who received epidural analgesia had lower pain and fatigue scores, increased mobilization, and signi?cantly better Health-related quality of life scores.27A systematic review exam-ining the effect of regional anesthesia and analgesia on satisfaction noted that seven of 10 RCTs noted improvement of satisfaction with regional analgesic techniques com-pared with opioids; however, no study in this review used a validated instrument to assess satisfaction.28
Future Directions
Prevention of Chronic Postsurgical Pain
The incidence of chronic pain after surgery varies but may be quite high: 30% to 81% after limb amputation, 22% to 67% after thoracotomy, 17% to 57% after breast surgery, 6% to 56% after cholecystectomy, and 4% to 37% after hernia repair.29Both peripheral and central sensitization occur after surgery and may result in hyperalgesia and allodynia. It appears that the intensity of acute postoperative pain is a predictor of chronic postsurgical pain.29Although there is a lack of RCTs to examine this issue, a few RCTs have demonstrated a decrease in chronic postsurgical pain with use of pre-operative epidural analgesia.30,31
Obstructive Sleep Apnea
Obstructive sleep apnea presents multiple problems for the perioperative physician. There continues to be an increase in the number of obese patients (“at-risk” popula-tion) with 27% of adults having a body mass index greater than 30 kg/m.32Obstructive sleep apnea may contribute to perioperative complications, particularly cardiac and pulmonary events. Sedatives and opioids may increase the risk of airway obstruction and the use of regional anesthesia–analgesia with a local anesthetic-only regimen might reduce this risk33; however, there are no adequate RCTs to guide our decisions for pain management and analgesia for patients with obstructive sleep apnea.
Summary
The pathophysiological changes attendant to surgery, anesthesia, and recovery may contribute to adverse outcomes in the postoperative period. Although certain peri-operative analgesic techniques may improve outcomes, analgesic agents provide dif-
ACUTE PAIN MANAGEMENT233 ferent physiological and analgesic bene?ts and as a result, there may be differences in outcomes with different analgesic regimens. Available data have shown that post-operative epidural analgesia may be associated with a decrease in perioperative mor-tality and cardiovascular, GI, and pulmonary complications. Use of perioperative regional analgesia will provide superior analgesia and may also be associated with an improvement in patient-oriented outcomes. However, there are many methodological and study design-related issues that may obscure the interpretation of available data, and a de?nitive answer to whether one technique is “superior” to another is lacking.
References
1.Kehlet H, Holte K: Effect of postoperative analgesia on surgical outcome. Br J Anaesth 2001;
87:62–72.
2.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;
234:560–9.
3.Rigg JR, Jamrozik K, Myles PS, et al.;MASTER Anaesthesia Trial Study Group: Epidural anaes-
thesia and analgesia and outcome of major surgery: A randomised trial. Lancet 2002;
359:1276–82.
4.Nishimori M, Ballantyne JC, Low JH: Epidural pain relief versus systemic opioid-based pain
relief for abdominal aortic surgery. Cochrane Database Syst Rev 2006; 3:CD005059. 5.Werawatganon T, Charuluxanun S: Patient controlled intravenous opioid analgesia versus
continuous epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev 2005; 1:CD004088.
6.Choi PT, Bhandari M, Scott J, Douketis J: Epidural analgesia for pain relief following hip or
knee replacement. Cochrane Database Syst Rev 2003; 3:CD003071.
7.Liu SS, Block BM, Wu CL: Effects of perioperative central neuraxial analgesia on outcome
after coronary artery bypass surgery: a meta-analysis. Anesthesiology 2004; 101:153–61.
8.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;
321:1493.
9.Wu CL, Hurley RW, Anderson GF, et al.:Effect of postoperative epidural analgesia on mor-
bidity and mortality following surgery in Medicare patients. Reg Anesth Pain Med 2004;
29:525–33.
10.Warner DO: Preventing postoperative pulmonary complications: The role of the anesthesi-
ologist. Anesthesiology 2000; 92:1467–72.
11.Ballantyne JC, Carr DB, deFerranti S, et al.:The comparative effects of postoperative anal-
gesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, con-trolled trials. Anesth Analg 1998; 86:598–612.
12.Walder B, Schafer M, Henzi I, Tramer MR: Ef?cacy and safety of patient-controlled opioid
analgesia for acute postoperative pain. A quantitative systematic review. Acta Anaesthe-siol Scand 2001; 45:795–804.
13.Ballantyne JC, Carr DB, Chalmers TC, et al.:Postoperative patient-controlled analgesia: Meta-
analyses of initial randomized control trials. J Clin Anesth 1993; 5:182–93.
14.Hudcova J, McNicol E, Quah C, Lau J, Carr DB: Patient controlled intravenous opioid anal-
gesia versus conventional opioid analgesia for postoperative pain control: A quantitative systematic review. Acute Pain 2005; 7:115–32.
15.Mangano DT: Assessment of the patient with cardiac disease: An anesthesiologist’s para-
digm. Anesthesiology 1999; 91:1521–6.
16.Beattie WS, Badner NH, Choi P: Epidural analgesia reduces postoperative myocardial infarc-
tion: A meta-analysis. Anesth Analg 2001; 93:853–8.
17.Bauer AJ, Boeckxstaens GE: Mechanisms of postoperative ileus. Neurogastroenterol Motil
2004; 16(Suppl 2):54–60.
18.Jorgensen H, Wetterslev J, Moiniche S, Dahl JB: Epidural local anaesthetics versus opioid-
based analgesic regimens on postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane Database Syst Rev 2000; 4:CD001893.
234WU
19.Hodgson PS, Liu SS: Thoracic epidural anaesthesia and analgesia for abdominal surgery: Effects
on gastrointestinal function and perfusion. Ballieres Clin Anaesthesiol 1999; 13:9–22. 20.Elia N, Lysakowski C, Tramer MR: Does multimodal analgesia with acetaminophen, non-
steroidal antiin?ammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials. Anesthesiology 2005; 103:1296–304.
21.Hirsh J, Hoak J: Management of deep vein thrombosis and pulmonary embolism. A state-
ment for healthcare professionals. Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology), American Heart Association. Circulation 1996;
93:2212–45.
22.Bew SA, Bryant AE, Desborough JP, Hall GM: Epidural analgesia and arterial reconstructive
surgery to the leg: Effects on ?brinolysis and platelet degranulation. Br J Anesth 2001;
86:230–5.
23.Markel DC, Urquhart B, Derkowska I, Salvati EA, Sharrock NE: Effect of epidural analgesia
on venous blood ?ow after hip arthroplasty. Clin Orthop Relat Res 1997; 334:168–74.
24.Block BM, Liu SS, Rowlingson AJ, et al.:Ef?cacy of postoperative epidural analgesia: A meta-
analysis. JAMA 2003; 290:2455–63.
25.Wu CL, Cohen SR, Richman JM, et al.:Ef?cacy of postoperative patient-controlled and con-
tinuous infusion epidural analgesia versus intravenous patient-controlled analgesia with opioids: A meta-analysis. Anesthesiology 2005; 103:1079–88.
26.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; 102:248–57. 27.Carli F, Mayo N, Klubien K, et al.:Epidural analgesia enhances functional exercise capacity
and health-related quality of life after colonic surgery: Results of a randomized trial. Anes-thesiology 2002; 97:540–9.
28.Wu CL, Naqibuddin M, Fleisher LA: Measurement of patient satisfaction as an outcome of
regional anesthesia and analgesia: A systematic review. Reg Anesth Pain Med 2001; 26: 196–208.
29.Perkins FM, Kehlet H: Chronic pain as an outcome of surgery. A review of predictive factors.
Anesthesiology 2000; 93:1123–33.
30.Senturk M, Ozcan PE, Talu GK, et al.:The effects of three different analgesia techniques on
long-term postthoracotomy pain. Anesth Analg 2002; 94:11–5.
https://www.doczj.com/doc/533714271.html,vand’homme P, De Kock M, Waterloos H: Intraoperative epidural analgesia combined
with ketamine provides effective preventive analgesia in patients undergoing major diges-tive surgery. Anesthesiology 2005; 103:813–20.
32.O’Brien PE, Dixon JB: The extent of the problem of obesity. Am J Surg 2002; 184:4–8S.
33.Gross JB, Bachenberg KL, Benumof JL, et al.;American Society of Anesthesiologists Task Force
on Perioperative Management: Practice guidelines for the perioperative management of patients with obstructive sleep apnea: A report by the American Society of Anesthesiolo-gists Task Force on Perioperative Management of patients with obstructive sleep apnea.
Anesthesiology 2006; 104:1081–93.
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