• Brian A. Williams, MD

       INTRODUCTION

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 methodologie differences and problems present in available trial results influence both the interpretation and applicability of the trial results.⁸

       INTRAOPERATIVE BENEFITS OF REGIONAL ANESTHESIA

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

Clinical Pearls

  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

       POSTOPERATIVE BENEFITS OF REGIONAL ANALGESIA

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

Clinical Pearls

        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.

Clinical Pearls

        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.

Clinical Pearls

        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.

Clinical Pearls

        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 patientcontrolled 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

Clinical Pearls

Related posts:

Regional Anesthesia in the Patient with Preexisting Neurologic Disease. The History of Local Anesthesia. Stimulating Catheters. Ultrasound-Assisted Nerve Blocks in Adults. Histology of Peripheral Nerves. Supraclavicular Brachial Plexus Block.