Chapter 75. Effects of Regional Anesthesia & Analgesia on Perioperative Outcome

Patients with severe medical conditions who undergo surgery are at a higher risk for perioperative morbidity and mortality. These patients have limited physiologic reserves, which may be overwhelmed by the perioperative stress from the trauma of surgery. The use of perioperative regional anesthesia and analgesia may attenuate detrimental perioperative pathophysiology and potentially diminish the incidence of adverse patient outcomes including mortality and major morbidity.1–4 Because only limited data are available on the effect of perioperative peripheral anesthesia and analgesia, this discussion, like much of the available data, focuses on the perioperative use of neuraxial, particularly epidural, anesthesia and analgesia. Nevertheless, the general concepts behind the benefits of perioperative neuraxial anesthesia and analgesia may ultimately be applicable to peripheral anesthesia and analgesia.

In general, perioperative regional anesthesia and analgesia (as opposed to general anesthesia followed by systemic opioids for postoperative pain control), especially that using a local anesthetic-based solution, can provide superior analgesia and attenuate adverse perioperative pathophysiology, particularly the neuroendocrine stress response. These benefits potentially can translate into decreased incidence of morbidity and mortality and to improved convalescence. Curiously, however, trials did not consistently document an improvement in these outcomes with the perioperative use of regional anesthesia and analgesia. Although some data support the use of perioperative epidural anesthesia and analgesia to decrease postoperative pulmonary, gastrointestinal, and cardiovascular complications,2–6 whether regional anesthesia is superior to general anesthesia in decreasing mortality is still controversial. Recent trials provide both supporting1 and refuting2,7 evidence. The various methodologic differences and problems present in available trial results influence both the interpretation and applicability of the trial results.8

A wide range of detrimental physiologic effects, such as the neuroendocrine stress response, hypercoagulation, immunosuppression, and impaired gastrointestinal and pulmonary function, occur as a result of surgical trauma. These effects contribute to the development of postoperative mortality and morbidity. Many of these adverse pathophysiologic responses begin in the intraoperative period and continue into the postoperative period, although the precise overall contribution of each period (intraoperative vs postoperative) to postoperative morbidity and mortality has not been fully evaluated. In a sense, these divisions (intraoperative vs postoperative) are artificial because most of these pathophysiologies follow a continuum from the intraoperative to postoperative period. However, elucidating the exact pathophysiology and differential contribution to postoperative morbidity and mortality would allow optimization of perioperative regional anesthesia and analgesia since different pathophysiologies will exhibit different peaks for the development of complications. For instance, the perioperative hypercoagulable state begins in the intraoperative period,9 but the majority of thromboembolic events occur well into the postoperative period. Likewise, the incidence of other complications, such as myocardial infarction and delirium, often peak in the postoperative period (eg, second or third postoperative day).10–12

Although many of the smaller randomized controlled trials failed to show a decrease in mortality rates with use of intraoperative regional anesthesia,2,7,13,14 all of these trials were underpowered to assess a rare outcome, such as death. A meta-analysis of randomized data (up to 1997) examining the effect of intraoperative neuraxial vs general anesthesia on mortality included a total of 141 trials with 9559 subjects. Results demonstrated that the use of perioperative neuraxial anesthesia reduced the overall mortality rate (primarily in orthopedic patients) by approximately 30%.1 Subgroup analysis showed that perioperative neuraxial anesthesia and analgesia decreased the odds of the development of deep venous thrombosis by 44%, pulmonary embolism by 55%, pneumonia by 39%, and respiratory depression by 59%, and reduced the need for transfusion by 55%. The majority of trials used in the meta-analysis compared intraoperative neuraxial anesthesia with general anesthesia, with only a few studies examining intraoperative epidural anesthesia followed by postoperative epidural analgesia.1

Although the majority of benefit trials focused on intraoperative neuraxial anesthesia vs general anesthesia, the role of postoperative regional analgesia on outcomes has not been evaluated extensively. As discussed previously, little data exist on the effect of postoperative peripheral analgesia on postoperative outcomes; the discussion here focuses primarily on postoperative epidural analgesia. Available data suggest that postoperative epidural analgesia may improve patient outcomes, including a decreased mortality rate.2–6,15 An analysis of the Medicare claims database from 1997 through 2001 noted that the use of postoperative epidural analgesia was associated with a significant decrease in 7-day [odds ratio = 0.52 (95% confidence interval: 0.38–0.73), p = 0.0001] and 30-day [odds ratio = 0.74 (95% confidence interval: 0.63–0.89), p = 0.0005] mortality rates after a variety of surgical procedures.15 Other benefits of perioperative epidural analgesia for decreasing morbidity are discussed later in this chapter; however, it must be kept in mind that some study design-related issues potentially limit the generalizability of these results to a broader surgical population.16–18

Cardiovascular Morbidity

Patients at risk for perioperative myocardial events have a higher incidence of myocardial ischemia and infarction. The stress of surgery or uncontrolled pain can activate the sympathetic nervous system, resulting in an imbalance between myocardial oxygen supply and demand and leading to myocardial ischemia and infarction.19 In addition, postoperative hypercoagulability can contribute to the myocardial oxygen imbalance and be an important factor in the development of perioperative myocardial ischemia and infarction.20 Perioperative myocardial infarction and other cardiovascular events, such as congestive heart failure, ventricular arrhythmias, and sudden death, occur with greater frequency within the first 2–3 days after surgery.12,21

Epidural analgesia may attenuate these adverse cardiovascular pathophysiologic events. Experimental studies demonstrate that thoracic epidural analgesia (TEA) will decrease cardiac sympathetic outflow; ease increases in heart rate, blood pressure, inotropy, and myocardial oxygen consumption; and result in a favorable myocardial supply and demand balance by improving coronary blood flow to subendocardial areas at risk for ischemia. These physiologic benefits were shown to reduce the anatomic extent of experimentally induced myocardial infarction and ischemia-induced malignant arrhythmias.22–24 Clinically, the effect of postoperative epidural analgesia on the incidence of myocardial ischemia or infarction in randomized trials is not known with certainty,13,25–29 although a meta-analysis revealed that the use of thoracic, but not lumbar, epidural analgesia significantly decreases the incidence of postoperative myocardial infarction.3 The benefits of thoracic but not lumbar epidural analgesia in decreasing adverse cardiovascular events, such as myocardial infarction, corroborates the findings of the physiologic benefits of TEA in experimental studies.

Coagulation-Related Morbidity

Coagulation-related complications, such as deep venous thrombosis and pulmonary embolism, are a major cause of morbidity and mortality following surgery.30,31 Patients are hypercoagulable postoperatively, in part, as a result of the neuroendocine stress response. Perioperative use of a local anesthetic-based neuraxial anesthetic and analgesic technique attenuate this hypercoagulable response by increasing peripheral blood flow, preserving fibrinolytic activity, easing increases in coagulation factors, and decreasing blood viscosity.32 A number of randomized trials and meta-analyses indicate that the use of perioperative regional anesthesia and analgesia (vs general anesthesia) will decrease the incidence of postoperative hypercoagulability-related events, such as deep venous thrombosis, pulmonary embolism, and vascular graft thrombosis.1,28,33,34 However, it is notable that many of these trial protocols did not use concurrent systemic thromboprophylaxis.

The effect of postoperative epidural analgesia per se on the development of hypercoagulability-related events is unclear. Some data demonstrate a lower incidence of deep venous thrombosis with use of postoperative epidural analgesia.35,36 Experimental data indicate a lack of physiologic benefits (eg, increased blood flow) when continuing epidural analgesia into the postoperative period.9 Similarly, Medicare claims analyses do not indicate that the presence of postoperative epidural analgesia will decrease the incidence of coagulation-related events.15,37 Further study is needed to determine if the addition of perioperative neuraxial anesthesia and analgesia to systemic thromboprophylaxis will lower the incidence of coagulation-related events.

Gastrointestinal Morbidity

One of the most feared postoperative gastrointestinal complications is ileus, which results in increased postoperative pain, prolonged hospital stays, pulmonary complications, septic complications, and decreased wound healing.6,38–42 The cause of postoperative ileus is multifactorial and includes the postoperative use of opioids, increases in sympathetic output (from the neuroendocrine stress response and uncontrolled pain), inputs from the systemic inflammatory response, and spinally mediated reflex arcs involving afferent stimuli (from somatic and visceral inputs) into the spinal cord and efferent stimuli from the sympathetic nervous system.5,38,42 TEA using a local anesthetic-based analgesic regimen may assuage some of these detrimental pathophysiologic effects and increase gastrointestinal motility and intestinal blood flow.5 TEA has many physiologic benefits, including increased gut mucosal blood flow,28 with the possible reduction of ileus after bowel ischemia,43 attenuation of somatic and visceral nociceptive afferent fibers of the spinal reflex arcs,5 and exertion of a beneficial physiologic and analgesic effect after systemic absorption of local anesthetic.44,45 In addition, epidural analgesia using a local anesthetic-based analgesic regimen decreases the amount of opioids used, which may facilitate return of gastrointestinal function.

Randomized controlled trial results suggest that when compared with systemic or neuraxial opioid analgesia, use of postoperative thoracic epidural analgesia with a local anesthetic-based regimen results in earlier return of gastrointestinal function. A systematic review of all randomized trial results demonstrated that epidural administration of local anesthetics (compared with systemic or epidural opioids) in patients undergoing abdominal surgery facilitates return of gastrointestinal function.46 In addition, thoracic epidural analgesia with local anesthetics may provide earlier fulfillment of discharge criteria.47,48 By contrast, use of epidural opioids, whether alone or in combination with local anesthetics, delays return of gastrointestinal motility compared with that seen in patients who receive epidural local anesthetics alone.47,49–52

Pulmonary Morbidity

Pulmonary complications, such as pneumonia and respiratory failure, are important causes of postoperative morbidity and mortality and are an important contributor to prolonged hospital and intensive care unit stays.30,53 Altered pulmonary mechanics, inadequate analgesia, and systemic opioid analgesics contribute to perioperative respiratory complications, especially in patients receiving general anesthetic agents. These agents suppress the activation of respiratory muscles, resulting in uncoordination of respiratory muscle activity54 and possibly decreased functional residual capacity (FRC) and atelectasis. In addition, spinal reflex inhibition of the phrenic nerve (with a resultant decrease in diaphragmatic function) also decreases FRC and can result in atelectasis. Finally, poor pain control can result in shallow breathing and interfere with the patient's ability to participate with respiratory therapy such as incentive spirometry.

Use of a local anesthetic-based epidural regimen may reduce some of these adverse pathophysiologic changes by attenuating reflexive spinal inhibition of diaphragmatic activity, preserving hypoxic pulmonary vasoconstriction in poorly ventilated segments of lung, and decreasing the use of systemic opioids. The regimen provides superior analgesia and allows patients to fully participate in rehabilitative physiotherapy.55,56 Despite some controversy regarding the precise definition of pulmonary complications, randomized controlled trial results and meta-analyses demonstrated improved patient outcomes with the perioperative use of epidural techniques. Two meta-analyses demonstrated a decrease in the incidence of atelectasis, respiratory complications, and respiratory depression with perioperative use of regional anesthetic and analgesic techniques.1,4 Use of epidural anesthesia–analgesia was superior to intercostal blocks, wound infiltration, or intrapleural analgesia in decreasing the incidence of pulmonary complications.4 Recent findings of a large, randomized controlled trial corroborated the findings of these meta-analyses. In these trial results, high-risk patients undergoing abdominal surgery who had perioperative epidural anesthesia and analgesia (vs those without perioperative epidural analgesia) had a significantly lower incidence of respiratory failure.3 Perioperative use of epidural analgesia also was shown to decrease pulmonary complications, decrease the incidence of dysrythymias, and facilitate postoperative extubation, resulting in a shorter length of intensive care unit stay for thoracic and cardiac bypass surgical patients.57–59

Patient-Oriented Outcomes

Assessment of patient-oriented outcomes, unlike that seen with “traditional” outcome studies, which focus on major morbidity and mortality, incorporates many different domains, including physiologic endpoints, adverse events, and psychosocial status. These “nontraditional” outcomes are recognized as valid and important outcome measurements in clinical care and research and reflect the global increased interest in patient-focused assessments. The perioperative use of regional anesthesia–analgesia (vs general anesthesia followed by systemic opioids) offers many advantages that may translate into improvements in many patient-oriented outcomes, including satisfaction, quality of recovery, and quality of life.60 Compared with systemic opioids, epidural analgesia provides superior postoperative pain control. A systematic review, including nonrandomized trial results, revealed that intramuscular (IM) analgesia and intravenous patient-controlled analgesia (IVPCA) resulted in a higher incidence of moderate-to-severe and severe pain vs epidural analgesia (moderate-to-severe pain: 67.2% for IM, 35.8% for IVPCA, and 20.9% for epidural analgesia; severe pain: 29.1% for IM, 10.4% for IVPCA, and 7.8% for epidural analgesia).61

These results were similar to meta-analysis findings in a review of randomized trials comparing epidural analgesia with systemic opioids. These trails found that epidural analgesia provided better overall postoperative analgesia than systemic opioids on each postoperative day up to 4 days after surgery.56 When analyzed by types of surgery and pain assessments, all forms of epidural analgesia provided significantly better postoperative analgesia than systemic opioids, with the exception of thoracic epidural analgesia vs opioids for rest pain after thoracic surgery. Thus, it appears that epidural analgesia, regardless of analgesic agent, location of catheter placement, and type and time of pain assessment, provides superior postoperative analgesia to systemic opioids.56

The superior analgesia conferred by epidural (and presumably peripheral) analgesia may result in an improvement in patient-oriented outcomes. A systemic review examining the issue of patient satisfaction indicated that the use of both neuraxial and peripheral regional analgesic techniques resulted in higher patient satisfaction compared with those for systemic opioids.62 In addition, when compared with systemic opioids, use of epidural analgesia is associated with an improved health-related quality of life (HRQL) in the postoperative period.63,64 Despite the fact that patient satisfaction and quality of life are complex and difficult to measure properly, it appears that perioperative regional analgesia, in part because of the superior analgesia provided, improves patient-oriented outcomes such as patient satisfaction62 and HCQL.63,64

“Epidural Analgesia” as a Generic Entity: Implications for Interpreting Its Effect on Patient Outcomes

Despite the affirmative data on improved patient outcomes with use of postoperative regional analgesia,2–6 one of the major issues in the overall interpretation of results from these and other trials is the fact that “epidural analgesia” is commonly viewed as a generic entity. This is unfortunate because different parameters in the regional analgesic technique (ie, location of catheter placement, analgesic agents used, and duration of epidural analgesia) influence the efficacy of these techniques on patient outcomes. For example, the effect of postoperative epidural analgesia on outcomes is optimized with the use of a “catheter incision-congruent” technique, which implies placement of the epidural catheter in a location corresponding to the dermatomes of the surgical incision. Catheter incision-congruent (vs catheter incision-incongruent) catheter placement confers superior physiologic and analgesic benefits.65,66

For example, high-risk cardiovascular patients undergoing upper abdominal or thoracic procedures may benefit from the use of TEA (catheter incision-congruent), which results in increases in coronary flow to subendocardial and ischemic areas and attenuation of sympathetically mediated coronary vasoconstriction,23,67–69 both of which can contribute to decreased incidence of myocardial infarction.3 In addition, for patients undergoing abdominal surgery, catheter incision-congruent (thoracic) catheter placement can result in the physiologic benefits of splanchnic sympathetic nervous system blockade, reduced inhibitory gastrointestinal tone, and increased intestinal blood flow,5 all of which facilitate return of gastrointestinal function. Trial results consistently demonstrate a benefit from catheter incision-congruent epidural analgesia (vs systemic opioids) in the return of gastrointestinal function; however, these benefits do not appear in those studies that used catheter incision-incongruent epidural analgesia.5 Thus, the differential physiologic and analgesic benefits of catheter incision-congruent analgesia improve patient outcomes.

In addition to the location of catheter placement, the specific analgesic agents (eg, opioids vs local anesthetics) influence patient outcomes. Despite the fact that neuraxial opioids are effective in controlling postoperative pain,70 only epidural local anesthetics, through blockade of afferent and efferent signals to and from the spinal cord, suppression of the surgical stress response,71 and prevention of spinal reflex inhibition of diaphragmatic and gastrointestinal function, have the ability to attenuate the adverse pathophysiologic responses that contribute to morbidity following surgery. Compared with neuraxial opioids, epidural local anesthetics may improve patient outcomes by allowing an earlier recovery of gastrointestinal motility after abdominal surgery47,49–51 and reduced incidence of pulmonary complications.4

The duration of epidural analgesia may be another important factor in improving patient outcomes. Because many of the perioperative pathophysiologic responses that begin intraoperatively continue into the postoperative period, patients may not receive the full physiologic and analgesic benefits from epidural catheters that are prematurely removed or dislodged. For instance, facilitated return of gastrointestinal function was documented only in subjects that retained epidural analgesia for longer than 24 h compared with those who received epidural analgesia for less time.5,72–75 In addition, postoperative but not intraoperative epidural analgesia appears to decrease the incidence of myocardial infarction, which correlated to the peak incidence of myocardial infarction between 24 and 48 h after surgery.3,21

Finally, the incorporation of perioperative regional analgesia into a multimodal approach to patient convalescence appears to maximize the analgesic and physiologic benefits of the regional technique. By controlling perioperative pathophysiologic responses through attenuation of the neuroendocrine stress response, effective pain control, earlier mobilizing of patients, and facilitated return of gastrointestinal function to allow early enteral feeding, perioperative regional anesthetic and analgesic techniques are an important and integral part of a multimodal approach to patient convalescence.76 A decrease in hormonal and metabolic stress and improvement in convalescence was demonstrated in patients undergoing other major procedures and participating in a perioperative multimodal pathway.77 Study results indicate that postoperative regional analgesia as part of a multimodal approach to patient convalescence can result in a shorter time to extubation, superior analgesia, earlier return of bowel function, and earlier fulfillment of intensive care unit discharge criteria in patients undergoing abdominothoracic esophagectomy.78 In addition, patients undergoing colon resection and receiving a multimodal approach to patient convalescence incorporating epidural analgesia had a reduced the length of hospitalization (from 6 to 10 days to a median of 2 days).79 Thus, it appears that utilizing a multimodal approach to patient convalescence that incorporates perioperative regional anesthetic and analgesic techniques may control perioperative pathophysiologic responses and result in accelerated patient recovery and decreased length of hospitalization.80

Postoperative cognitive disorders (PCD) include a broad spectrum of impairments in cognitive function and memory or of consciousness with a common denominator of deficits in cognition and memory.81 PCD can occur after surgery, with mental function typically reaching a nadir in the early postoperative period and returning to preoperative levels in the majority of patients at 1 week following surgery.82,83 Certain patients are at higher risk for the development of PCD or long-term PCD. These populations include those undergoing certain types of surgery or those with coexisting medical diseases, preoperative cognitive dysfunction, and advanced age.10,84 Recent data indicate that PCD in high-risk patients may occur more commonly than previously thought. A trial enrolling approximately 1200 patients older than age 60 years showed that PCD was present in 25.8% of patients 1 week postoperatively and 9.9% of patients 3 months after surgery, compared with 3.4% at 1 week and 2.8% at 3 months, respectively, for nonsurgical control patients.84 Furthermore, postoperative delirium, a particularly problematic form of PCD, may occur in 9% to 11% of elderly patients undergoing elective noncardiac surgery.85,86 For instance, up to 37% of elderly patients undergoing hip fracture repair may experience PCD.10

The reason that PCD is especially significant is that its presence is an independent predictor of short- and long-term outcomes (eg, increased mortality, higher rates of major complications, longer lengths of stay, and higher rates of discharge to rehabilitative facilities), even after adjusting for age, comorbidities, and functional status.87–90 Delirium in hospitalized patients contributes to an additional 17.5 million inpatient days and $4 billion in health care expenditures annually.89 Decreased neurocognitive function results in a significant decrease in health-related quality of life, with an equally adverse social and financial effect for patients and their caregivers.91 In addition, the presence of PCD may be a surrogate for the quality of the hospital care.89 Finally, the incidence of PCD will continue to increase because the percentage of elderly people in the United States is estimated to increase to approximately 17% by 2020, with approximately 40% of all health care dollars spent on this population (≈5% of the US gross domestic product).92

Although the precise cause of PCD is unknown, a multifactorial cause without a final common pathway appears to be the most reasonable explanation based on available studies.93,94 In general, the most common hypotheses focus on a perioperative imbalance of neurotransmitters, especially of acetylcholine and serotonin, in the presence of a decreased neurophysiologic reserve, which is seen in elderly patients.95–98 Others hypotheses revolve around the presence of inflammatory mediators, such as cytokines, in the development of PCD.99 Thus, the trauma of surgery may disrupt normal neurotransmitter activity, release inflammatory mediators, and result in hormonal imbalances that contribute to the development of PCD, especially in vulnerable populations with decreased neurophysiologic reserves.97

Because PCD has a multifactorial cause, many risks factors may contribute to its development. Preoperatively, patients who are elderly10,85,94 or those who have poor preoperative cognitive10,85,94,100 or functional status94,101 are at higher risk for developing PCD. The presence of a history of alcohol abuse or marked abnormalities in preoperative sodium, potassium, or glucose levels may also be predictors for the development of PCD.94,102–104 Intraoperatively, certain types of surgical procedures (eg, cardiac surgery with cardiopulmonary bypass,105 aortic aneurysm repair,94 and orthopedic procedures in elderly patients101,106,107) are associated with higher rates of PCD. Cerebral hypoperfusion or abnormalities in intraoperative glucose and hematocrit levels do not appear to correlate with PCD.108,109 The correlation of sustained and profound hypotension, hypoglycemia, anemia, or hypoxia to the development of PCD is unclear. A longer duration of surgery and anesthesia is associated with an increase in the incidence of PCD.84,110 Postoperatively, the use of anticholinergic drugs, meperidine, and benzodiazepines, is associated with the development of PCD.10,86,111 Complications, such as postoperative infections and respiratory complications, are also associated with the development of PCD.84 Finally, increased levels of postoperative pain are associated with a higher incidence of PCD.11,112,113

Although the use of perioperative regional anesthesia and postoperative analgesia may be associated with a decrease in perioperative mortality and morbidity1–4 in high-risk patients, the effect of perioperative regional anesthesia on PCD is unclear. Data from examination of the effect of peripheral nerve anesthesia and analgesia on PCD are limited, and the remainder of this discussion focuses on neuraxial techniques. Although a large number of randomized trials comparing intraoperative neuraxial with general anesthesia showed that the use of perioperative neuraxial anesthesia does not decrease the incidence of PCD, methodologic issues present in the study designs preclude a definitive answer about whether perioperative regional anesthesia influences the development of PCD.

A systematic review of the available published study results examining the effect of perioperative neuraxial anesthesia on cognitive function noted that of the 24 studies examined, 19 were randomized and 4 were nonrandomized trials.114 Of the 19 randomized trials, 18 did not demonstrate a difference in cognitive function between intraoperative general anesthesia and neuraxial anesthesia. None of the five nonrandomized trials demonstrated a difference between in cognitive function as a result of intraoperative general anesthesia and those after neuraxial anesthesia. Based on this review, it appears that intraoperative neuraxial anesthesia alone does not have an effect on PCD; however, the presence of methodologic issues and the lack of examination of the effect of postoperative regional analgesia on the development of PCD are issues for future study.

All available studies have some degree of methodologic and study design issues, revolving around the definition of cognitive dysfunction, properties of the specific neuropsychological tests used, statistical considerations, and lack of control for postoperative pain, which may be confounding factors in interpreting these trial results.115–117 The precise definition of cognitive dysfunction and the determination of how it is measured are important because cognitive function is an abstract concept consisting of domains of memory, attention, language, visual–spatial ability, abstraction, and psychomotor performance.116 The definition of a postoperative cognitive deficit is not standardized and may be arbitrarily chosen based on a change in test performance (eg, 1 standard deviation).115 The presence of a cognitive deficit may be based on just the presence of a change in one or two domains, which can easily occur when a large number of tests are used to assess PCD.115,118 Using a large number of tests increases the chance of patient withdrawal and fatigue, which in itself may affect test results. Thus, the wide range in incidence of PCD may be due, in part, to the definition and criteria of cognitive deficit chosen by the investigator. In addition, the neuropsychological tests used to assess PCD in the study may not be ideal in this setting because the majority of tests were designed for long-term cognitive performance in broader population-based studies or in subjects with dementing illnesses (eg, Alzheimer's disease).117,119 Finally, the significance of the statistical analysis is limited because the accurate interpretation of large numbers of neuropsychological tests must be done with caution.115,118

Probably the area of most concern is the lack of control for postoperative analgesia in currently available trial results. In general, studies indicate that higher levels of postoperative pain are associated with a higher incidence of PCD (especially delirium).11,113 Based on these results, it would seem that control of postoperative pain might theoretically decrease the incidence of PCD, which typically peaks within the first 3 postoperative days.10 The implication here is that different analgesic regimens, which provide different levels of postoperative analgesia with varying side effects, may potentially result in a different incidence of PCD or level of postoperative cognitive function. This implication is especially important for postoperative regional (both neuraxial and peripheral) techniques because these analgesic regimens (especially the use of a local anesthetic-based solution) were shown to not only provide superior pain control versus systemic opioids56,61 but also minimize the systemic effects of opioids, which may be associated with development of postoperative cognitive dysfunction.94 In addition, epidural analgesia may decrease the incidence of postoperative respiratory complications,1,4 which were shown to be associated with a higher incidence of PCD.84 Thus, future evaluation of postoperative regional analgesia on PCD may be at least as important as the effects of intraoperative neuraxial anesthesia, particularly because the postoperative delirium peaks in the second or third postoperative day.

In summary, PCD includes a broad assortment of disorders with many diverse clinical presentations and a multifactorial cause. PCD is an important marker for short- and long-term outcomes. The development of PCD has many risk factors, and certain surgical populations are at higher risk. Although the available data suggest that intraoperative neuraxial anesthesia does not decrease the incidence of PCD compared with general anesthesia, many methodologic and design issues affect the interpretation of some of these studies. Future work in this area should focus on the effect of various postoperative analgesia regimens and techniques on the development of PCD.