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Perioperative Management

Kirsten Bass Wilkins, M.D.
Clinical Assistant Professor of Surgery
UMDNJ-Robert Wood Johnson
New Brunswick, New Jersey

Introduction

The colorectal surgical patient often has comorbid medical conditions other than the one (e.g. diverticulitis, malignancy, inflammatory bowel disease, etc.) that has brought the patient to the attention of the colorectal surgeon. To this end, careful preoperative assessment and utilization of risk stratification strategies are an important part of the initial evaluation of the patient. This approach is necessary in order to accurately obtain informed consent from the patient, but, more importantly, to implement perioperative management strategies to reduce perioperative risks and length of stay. This review focuses on developments in this arena since it was last presented as a Core Subject in 2000.

Preoperative Risk Assessment

Elective abdominal colorectal operations are often performed for conditions such as malignancy in which the decision to operate may be made regardless of the risks that may be associated with the procedure. Despite this, assessment of perioperative risk is important for several reasons. First, assessment of risk is necessary so that the surgeon can discuss with the patient the likelihood of potential morbidity and mortality such that proper informed consent may be obtained. More importantly, an understanding of an individual patient’s particular risks should allow for the implementation of periopertive strategies to help reduce the chances of morbidity and mortality. Serious cardiac and pulmonary complications are responsible for significant morbidity and mortality in association with major abdominal surgery, therefore much of the literature focuses on cardiac and pulmonary risk assessment.

Before utilizing any specific risk assessment tools, a careful history, review of systems, and physical examination should be obtained. Care should be taken to also assess the patient’s functional capacity (e.g. ability to perform activities of daily living, exercise tolerance, etc.) After this is accomplished, appropriate preoperative laboratory, radiologic, and cardiac testing can be ordered. In the world of cost containment, it should be noted that very little knowledge will be obtained through the routine acquisition of complete blood counts, metabolic panels, and coagulation profiles in patients in whom the history and physical do not warrant such testing. Obviously, there are patients in whom directed laboratory testing will be of use (e.g. hematocrit in patients with history of bleeding, electrolytes in patients with renal disease or on diuretics, coagulation profile in patients with a history of a bleeding disorder). In reality, however, many hospitals have instituted preoperative admission testing algorithms that require the acquisition of a panel of laboratory tests, a baseline chest x-ray, and an electrocardiogram in men over the age of 40 and women over the age of 50, leaving the surgeon very little choice in which testing he/she would like to obtain.

Once a patient has been identified following routine history and physical to possibly be at risk for cardiac complications, a multitude of indexes may be utilized to assess cardiac risk in noncardiac surgical patients. In 1977, Goldman et al, published a multifactorial risk index of cardiac risk in noncardiac surgical procedures that identified nine independent correlates of life-threatening and fatal cardiac complications. (1) Since then, a significant amount of literature has focused on cardiac risk stratification. Two recent strategies worth noting include the Revised Cardiac Risk Index (2) as proposed by Lee et al and the ACC/AHA guidelines (3) published in 2002. The Revised Cardiac Risk Index published in 1999, evaluated 4315 patients ³ the age of 50 undergoing major noncardiac procedures. Six independent predictors of major cardiac complications were identified including high-risk surgery (abdominal surgery is high risk), history of ischemic heart disease, history of congestive heart failure, history of cerebrovascular disease, preoperative treatment with insulin, and preoperative serum creatinine greater or equal to 2.0 mg/dl. Rates of major cardiac complications in patients with 0, 1, 2, or ³ 3 or more of these risk factors were 0.4%, 0.9%, 7%, and 11%, respectively. (2) The 2002 ACC/AHA guidelines represent an update of guidelines which were first published in 1996. These guidelines were developed after careful review of all relevant literature relating to preoperative cardiac evaluation in noncardiac surgery. The ACC/AHA guidelines propose an eight step algorithm to assess which patients may benefit from further cardiac testing based on a combination of factors including whether or not the patient has undergone coronary revascularization within the last five years, recent cardiac signs and symptoms, clinical predictors, the functional capacity of the patient, and the risk of the surgical procedure (abdominal surgery is high-risk). In the ACC/AHA guidelines major clinical predictors include unstable coronary syndromes, decompensated congestive heart failure, significant arrythmias, and severe valvular disease. Intermediate clinical predictors include mild angina pectoris, prior myocardial infarction, compensated or prior congestive heart failure, diabetes mellitus, and renal insufficiency. Minor clinical predictors include advanced age, abnormal electrocardiogram, rhythm other than sinus, low functional capacity, history of stroke, and uncontrolled systemic hypertension. Following the algorithm will allow for decisions regarding whether or not further noninvasive cardiac testing (e.g exercise stress test, dobutamine echocardiography, or dipyridamole thallium nuclear imaging) or invasive cardiac testing (coronary angiography) is required. Patients identified with significant ischemic heart disease are then preoperatively managed in one of three ways: revascularization by surgery, revascularization by percutaneous coronary intervention (e.g. angioplasty or stents), or medical management alone. One overriding theme of the ACC/AHA guidelines is that preoperative intervention is rarely necessary simply to lower the risk of surgery. Rather, such an intervention should be indicated irrespective of the preoperative context to improve short- and long-term cardiac outcomes. The Coronary Artery Surgery Study (CASS) database revealed that patients who had coronary artery bypass graft (CABG) before high risk surgery did better than those patients who did not undergo CABG preoperatively. (4) However, patients had to survive CABG before they could undergo the elective noncardiac surgery. In general, patients who should undergo preoperative surgical revascularization are those whose long-term outcomes would be improved by CABG. CABG should not be done just to get the patient through the noncardiac surgery. Percutaneous coronary intervention may also be utilized preoperatively, however, careful consideration must be given before this strategy is undertaken. Currently, angioplasty is frequently accompanied by coronary stent placement. After stent placement, postprocedure antiplatelet therapy is instituted to prevent acute coronary thrombosis and maintain long-term stent patency. It is strongly suggested that elective surgery be delayed 4-6 weeks in such patients to allow complete endothelialization of the stent and to complete the suggested course of antiplatelet therapy. Surgery before this time period risks bleeding if the patient is still on antiplatelet therapy and stent thrombosis if the antiplatelet therapy is stopped prematurely.(5)

Because of the limitations associated with CABG and percutaneous coronary intervention, medical therapy is the most likely intervention to be recommended in the colorectal surgery patient with cardiac risk factors. These are medications that will not only be used perioperatively but also in the long-term management of the patient. In general, patients with angina should receive aspirin, nitrates, beta-blockers, and calcium channel blockers. Following a myocardial infarction, the patient should be on aspirin, beta-blockers, and usually a statin. Hypertensive patients are frequently optimized on beta-blocker therapy. An angiotensin-converting enzyme inhibitor is frequently utilized in addition to beta-blockers in patients with congestive heart failure or diabetes. (5,6,7) One overriding theme that should be obvious is that beta-blockers are almost always indicated in the medical management of the above patients. Importantly, several randomized trials have demonstrated that the perioperative administration of beta-blockers is associated with decreased perioperative cardiac events and mortality (8) as well as improved six month survival due to a reduction in cardiac events (9) in patients undergoing noncardiac surgery. ACC/AHA guidelines suggest that beta-blockers should be started as soon as possible before surgery and titrated to a dose to achieve a resting heart rate between 50 and 60 beats per minute. The beta-blocker is then continued intraoperatively and postoperatively. Again, in the postoperative period care must be taken to ensure that the target heart rate is achieved. (3) In patients in whom beta-blockers are contraindicated there may be a role for alpha-2 adrenergic agonists (e.g. mivazerol) which by virtue of their central action have analgesic, sedative, and sympatholytic effects. (3,5,10)

Intraoperative management strategies that may be implemented to decrease cardiac risk are delegated by the anesthesiologist, but surgeons and anesthesiologists should always work as a team aiming for the best possible outcome for the patient. All anesthetic techniques and agents have known cardiac effects. The prevalence of postoperative cardiac morbidity and mortality does not seem to be significantly different whether regional or general anesthesia is utilized. Maintenance of normothermia is of paramount importance and has been associated with a reduced incidence of perioperative cardiac events. Controversy still exists regarding the use of intraoperative pulmonary artery catheters (PAC). Factors that should be considered when deciding whether or not to use a PAC are the severity of the patient’s cardiac disease, the risk of severe fluid shifts associated with the proposed surgery, complications associated with PAC use, and the experience of the team in utilizing this technique of monitoring. (3,5)

Postoperatively, care should be taken to ensure that all patients have adequate pain control whether by patient controlled analgesia, epidural analgesia, or other means. Inadequate pain control can lead to catecholamine surges and possible cardiac complications. It should be noted that formerly most perioperative myocardial infarctions were felt to occur on postoperative day three, but more recent data suggests that they are more likely to occur within the first forty-eight hours following surgery. (5) In addition, as many as 95% of postoperative ischemic events may be silent and without chest pain. In patients with known or suspected coronary disease, electrocardiograms should be obtained at baseline, immediately after surgery, and on the first two days after surgery. (3,7,11) Routine measurement of postoperative creatine kinase-MB and troponin is best used in high-risk patients or in those with clinical, electrocardiographic, or hemodynamic indicators of cardiovascular dysfunction.

Further information on the ACC/AHA guidelines is available at the ACC website: http://www.acc.org.

Although postoperative pulmonary complications are common and up to one quarter of deaths occurring within one week of surgery are related to these complications, few studies have been conducted to validate pulmonary risk indexes in the noncardiac surgery patient. Important postoperative pulmonary complications include pneumonia, respiratory failure with prolonged mechanical ventilation, bronchospasm, atelectasis, and exacerbation of underlying chronic lung disease. Patient related risk factors that are known to contribute to postoperative pulmonary complications include smoking, overall health status and functional capacity, and the presence of chronic obstructive pulmonary disease. Obesity, despite common assumption, is not a significant risk factor for pulmonary complications. Procedure-related risk factors also contribute to pulmonary complications, and the surgical site is the most important predictor of pulmonary complications with upper abdominal and thoracic surgery carrying the highest risk of 10 to 40%. Duration of surgery of longer than three hours also increases the risk of postoperative pulmonary complications. Most studies have shown lower rates of pulmonary complications when epidural or spinal anesthesia is utilized compared to general anesthesia.(12) In 2001, Arozullah et al developed and validated a multifactorial risk index for predicting postoperative pneumonia after noncardiac surgery which takes many of the above mentioned factors into account. (13) In this study, 1.5% of patients developed postoperative pneumonia, however, the 30-day mortality was 21% in patients with pneumonia versus 2% in those without postoperative pneumonia.

Preoperative pulmonary assessment is best completed by a careful history focused on exercise tolerance and a physical examination to detect decreased breath sounds, wheezes, rhonchi, and a prolonged respiratory phase. This directed history and physical is more useful than obtaining routine preoperative pulmonary function tests except in patients undergoing thoracic surgery. Pulmonary function tests, however, may be useful in patients with chronic obstructive pulmonary disease to assess whether they have achieved maximum benefit from medical therapy.

Pulmonary risk reduction strategies may be divided into preoperative, intraoperative, and postoperative interventions. All patients should be encouraged to stop cigarette smoking for as long as possible before surgery. Patients should also be educated preoperatively in lung-expansion maneuvers including deep-breathing exercises and incentive spirometry. These exercises have consistently been shown to reduce postoperative pulmonary complications by 50%.(12) Patients with chronic obstructive pulmonary disease should be treated with inhaled ipatropium with the addition of inhaled beta-adrenergic-receptor agonists as needed. A preoperative course of corticosteroids is occasionally indicated in patients who have not been optimized with bronchodilator therapy. Asthmatic patients are also treated with bronchodilators and should be free of wheezing before surgery. Again, corticosteroids may be necessary to optimize the patient for surgery. Intraoperative strategies to reduce pulmonary complications include limitation of surgery to less than three hours if possible and the use of laparoscopy to avoid upper abdominal incisions if possible. It must be remembered, however, that certain patients with severe pulmonary disease may be unable to tolerate the pneumoperitoneum needed for laparoscopy due to carbon dioxide retention and elevated pulmonary pressures. Avoiding general anesthesia will decrease risk, but may not be practical. Postoperatively, assuring adequate pain control is paramount and may be best achieved with the use of epidural analgesia which in most studies has been associated with decreased pulmonary complications. (12) Continuation of incentive spirometry and deep-breathing exercises is also encouraged. Interventions that may be useful to decrease the incidence of ventilator-associated pneumonia include elevation of the head of the bed to at least 45 degrees in order to reduce gastroesophageal reflux and aspiration and the avoidance of H2-antagonists in patients at low to moderate risk of gastrointestinal bleeding as gastric colonization by potentially pathogenic organisms increases with decreasing gastric acidity. It is commonly assumed that small intestinal versus gastric feeding is safer in intubated patients, but this has not been supported by recent studies. (14)

Mechanical Bowel Preparation

One of the most controversial topics in colon and rectal surgery today is whether or not there is any benefit of the preoperative utilization of a mechanical bowel preparation. Over the years, many different authors have attempted to address this issue, but it is difficult to make meaningful comparisons between these different studies for several reasons. There is wide variation in these studies concerning the additional use of oral antibiotic preparations and the use of intravenous antibiotics. There is also variation in the antibiotics of choice and the duration of perioperative antibiotics. While most of these studies show no added benefit of a mechanical bowel preparation, most of these studies include only a small number of patients.

Proponents of the elimination of mechanical bowel preparation point to the trauma literature where it has been shown to be safe to repair and resect colonic injuries where, obviously, no mechanical bowel preparation has been performed. It is also felt that a mechanical bowel preparation just converts solid stool to liquid stool with no effect on bacterial counts. This claim is actually supported by the findings of Nichols et al in 1973 and was part of the rationale for administering the preoperative oral antibiotic bowel preparation. (15) Proponents also state that liquid stool is more difficult to control than solid stool which may lead to easier leakage of stool during intraoperative bowel manipulation during anastomosis. Note is also made of patient discomfort associated with mechanical bowel preparation (e.g. nausea, vomiting, etc.) and possible electrolyte abnormalities and dehydration with certain preparations.

Those who favor mechanical bowel preparation claim that the absence of solid stool makes it easier to palpate lesions during an open operation. Some surgeons point out that a colon full of solid stool is more difficult to manipulate in the laparoscopic setting. Obviously, a mechanical bowel preparation must be used if there is a chance that intraoperative colonoscopy may be necessary.

One recent prospectively, randomized controlled trial compared the use of a mechanical bowel preparation of polyethylene glycol with no mechanical bowel preparation in patients undergoing elective colon and rectal resections with primary anastomosis. All patients did receive oral antibiotic bowel preparation with neomycin and erythromycin as well as perioperative intravenous antibiotics that were continued for at least twenty-fours hours postoperatively. In this 2003 study of 380 patients, Zmora et al reported no difference in the rate of wound infection, anastomotic leak, and intra-abdominal abscesses. (16)

Despite the fact that the surgical literature does not clearly show a benefit of the utilization of preoperative mechanical bowel preparation, a recent survey shows that 99% of members of the American Society of Colon and Rectal Surgeons use it, although 10% of these surgeons questioned its importance. (17)

Several options are available for mechanical bowel preparation if one is to be utilized. The most commonly used preparations are polyethylene glycol and sodium phosphate preparations. Polyethylene glycol is an osmotically balanced, electrolyte solution which while it requires the ingestion of a large volume (4 liters) to be effective, no significant electrolyte or metabolic abnormalities result from its use. Reduced-volume lavage solutions which incorporate bisacodyl as part of the preparation are also available. Oral sodium phosphate solutions are commonly used as well, but they contain 48g of monobasic sodium phosphate and 18g of dibasic sodium phosphate per 100 ml, thus making it a very hypertonic solution. Because of this, adequate oral fluids must be taken with the preparation to avoid the development of dehydration and hypovolemia which can occur, especially in elderly patients. Furthermore, electrolyte abnormalities, most notably hyperphosphatemia, may occur. Transient hypernatremia, hypokalemia, and hypocalcemia may also occur. While most patients are not affected by these electrolyte abnormalities, sodium phosphate preparation should be avoided in patients with renal disease, congestive heart failure, ascites, and in those who cannot adequately hydrate themselves. It should also be used with caution in patients taking diuretics and in the elderly. (18,19, 20, 21)

Perioperative Antibiotics

Perioperative antibiotic use by colon and rectal surgeons can be divided into oral and intravenous antibiotic prophylaxis. Since most colorectal infectious complications are caused by endogenous colonic bacteria, appropriate antibiotic regimens must cover aerobic coliforms (e.g. E. coli, Klebsiella, Proteus, etc.) as well as anaerobes (B. fragilis and Clostridia). Since Nichols et al revealed the importance of oral antibiotic bowel preparation with neomycin and erythromycin (without intravenous antibiotics) in the reduction of postoperative infections (15), many studies have been conducted looking at the effects of oral and intravenous antibiotic prophylaxis in colorectal surgery. Just as in the mechanical bowel preparation literature, it is difficult to compare many of the studies looking at the value of oral and intravenous antibiotics. Different antibiotics are used (both oral and intravenous), some studies do not utilize oral antibiotics while others do not use intravenous antibiotics, and the duration of intravenous antibiotics varies considerably. While controversy exists regarding the additive benefit of oral antibiotics when used in combination with intravenous antibiotics, most studies reveal that intravenous antibiotics are useful to reduce the rate of postoperative infections. (22,23) Today, the preoperative administration of intravenous antibiotics is considered the standard of care in most institutions. To be effective, the intravenous antibiotics must be administered within 1 hour of the incision, thus care should be taken to avoid ordering antibiotics "on call to OR" as time spent in preoperative holding areas may be prolonged. I have found it helpful to have intravenous antibiotics administered as the patient is being physically taken into the operating room. While it has been shown in a randomized trial that one preoperative dose is just as effective as three doses of prophylactic intravenous antibiotics (23), many surgeons do not comply with this recommendation. Clearly, intravenous antibiotics should not be continued for more than twenty-four hours postoperatively when being used prophylactically. Unnecessary antibiotic use is not without adverse consequence such as the development of bacterial resistance and the complication of Clostridium difficile infection. The reader is referred to an excellent review of mechanical bowel preparation and the use of oral and intravenous antibiotics in colorectal surgery by Zmora et al.(24)

Perioperative Blood Transfusion

Colorectal surgery patients are frequently anemic preoperatively secondary to chronic colonic blood loss (e.g. malignancy or inflammatory bowel disease) or other medical conditions (e.g. renal insufficiency, malnutrition, etc). Because of this, the colorectal surgeon is frequently faced with the question of when to transfuse a patient before surgery as well as in the intraoperative and postoperative periods. The risks of infectious disease transmission (e.g hepatitis and HIV) and possible transfusion reactions are often well appreciated. What is not as widely appreciated is the risk of immunosuppression associated with blood transfusion. Several studies have noted a markedly increased risk of postoperative infection in colorectal surgery patients who have required blood transfusion. (23, 25) More recently, several studies have examined the effect of transfusion in critically ill patients. In the TRICC trial (26), 838 critically ill patients were randomized to two groups: a restrictive group where transfusions were given only if the hemoglobin concentration fell below 7.0 g/dl and the hemoglobin level maintained between 7.0 and 9.0 g/dl and a liberal group where transfusions were given if the hemoglobin concentration fell below 10.0 g/dl and the hemoglobin level maintained between 10.0 and 12.0 g/dl. Overall, the 30-day mortality was the same between each group. However, subset analysis revealed that among less critically ill patients (APACHE score £ 20) and in patients less then 55 years of age, the mortality rate was much lower in the restrictive group. In patients with clinically significant cardiac disease, there was no difference in 30-day mortality between the restrictive and liberal groups. The mortality during hospitalization was significantly lower in the restrictive group. The authors concluded that a restrictive strategy of blood transfusion in critically ill patients is at least as effective and possibly superior to the liberal strategy of transfusion, with the possible exception of those with acute myocardial infarction or unstable angina. An additional prospective study in critically ill patients also demonstrated significantly higher mortality rates in matched patients receiving blood transfusions compared to those who had not been transfused. (27) All of these studies speculate that immunosuppression is responsible for the worse mortality associated with blood transfusion.

There is no specific hemoglobin level at which the colorectal surgeon should automatically transfuse a patient in the perioperative period. Each patient must be individually evaluated and the potential risks and benefits of transfusion or no transfusion weighed independently. However, in the stable patient without significant cardiac disease and no clinical symptoms from anemia (e.g. tachycardia, hypotension, dyspnea, etc), it is probably reasonable to accept a hemoglobin in the 7.0 g/dl range before considering blood transfusion. On the other hand, a patient with significant cardiac disease, with symptoms of anemia, or with expected significant blood loss in the planned operation should be transfused preoperatively up to a hemoglobin of 10.0 g/dl. The benefits of blood transfusion in elderly patients with acute myocardial infarction was observed in a large, retrospective study of transfusion and mortality in this group of patients. (28) The authors concluded that blood transfusion is associated with a reduction in 30-day mortality in elderly patients with acute myocardial infarction if the admission hematocrit is 30% or lower. Autologous blood donation and transfusion is rarely an option in the anemic patient, and likely will not alleviate the immunosuppressive consequences of transfusion. On the other hand, preoperative administration of recombinant human erythropoietin has been shown to reduce the need for postoperative blood transfusion in anemic patients undergoing colorectal surgery. (29)

Thromboembolic Prophylaxis

Patients undergoing colorectal surgery are often at an increased risk for venous thromboembolic complications. Risk factors for venous thromboembolism may be broadly divided into categories including venous stasis (e.g. age > 40, immobilization, varicose veins, anesthesia, etc.), endothelial damage (e.g. abdominal/pelvic surgery, prior deep venous thrombosis, trauma, etc.), and hypercoagulability (e.g. cancer, high estrogen states, positive family history, inflammatory bowel disease, sepsis, blood transfusions, elevated thrombophilia markers, etc.).(30) Patients at high risk are those undergoing major surgery who are older than 40 years of age or who have additional risk factors. The highest-risk patients are those undergoing major surgery who are older than 40 years old and have a history of prior venous thromboembolism, cancer, or other hypercoagulable state. Thus, the colorectal surgery patient undergoing an abdominal procedure is at least a high-risk patient and, often, considered to be the highest risk. The risk of thromboembolism in high-risk surgical patients who are not receiving prophylaxis is as follows: proximal deep venous thrombosis (DVT) (4-8%); clinical pulmonary embolism (PE) (2-4%); fatal PE (0.4-1.0%). In the highest-risk patient the risk is as follows: proximal DVT (10-20%); clinical PE (4-10%); fatal PE (0.2-5.0%). (31) In high-risk patients several methods of prophylaxis are available including low-dose unfractionated heparin (LDUH), low-molecular weight heparin (LMWH), or the use of intermittent pneumatic compression (IPC) devices (in patients considered to be at risk for bleeding). In the highest-risk patients, it has been recommended that pharmacologic anticoagulation (e.g. LDUH or LMWH) be combined with IPC devices and/or elastic graduated compression stockings (ES). (31, 32) IPC devices stimulate fibrinolytic activity. ES have been found to counteract venous stasis and augment venous return during abdominal insufflation during laparoscopic surgery. (31) Whatever method is chosen for prophylaxis, it is important that it be started before the induction of anesthesia and continued without interruption perioperatively. Accepted regimens are as follows: LDUH 5000 units SC starting 2 hours before surgery and continuing q8h; LMWH (enoxaparin) 40 mg SC starting 2 hours before surgery and continued daily; or IPC/ES started immediately before surgery and continued until the patient is fully ambulatory. (31) Several recent studies are worth discussion. In 2001, McLeod et al compared the use of subcutaneous heparin versus enoxaparin in patients undergoing colorectal surgery. Nine hundred thirty-six patients completed the randomized protocol and the rate of proximal DVT was the same in each group (2.6% in the heparin group versus 2.8% in the lovenox group). Only one patient in the enoxaparin group had a symptomatic, nonfatal PE. No deaths were attributable to thromboembolism. The rate of minor bleeding was significantly higher in the enoxaparin group, however, the rates of major bleeding and reoperation were low and not significantly different between the two groups. These authors concluded that because the cost of enoxaparin is higher than the cost of heparin with similar outcomes, heparin should remain the preferred method of prophylaxis. (33) However, patient and nursing acceptance of once daily dosing with enoxaparin should not be underestimated. The duration of prophylaxis is also controversial with some surgeons claiming that it should be continued after discharge from the hospital, especially since many patients are leaving the hospital in shorter periods of time. One recent study addressed this issue in which patients undergoing abdominal/pelvic surgery for cancer received enoxaparin daily for 6-10 days and then were randomized to receive either enoxaparin or placebo for an additional 21 days. The rates of venous thromboembolism at the conclusion of the trial were significantly different with a rate of 12.0% in the placebo group versus 4.8% in the enoxaparin group. This difference also persisted at 3 months. (34) Finally, in patients considered to be at the highest risk of thromboembolic complications, and in whom it is felt unsafe to proceed with pharmacologic prophylaxis for whatever reason, consideration may be given to the placement of an inferior vena cava filter preoperatively.

While the benefits of pharmacologic prophylaxis are clear, it is also important to be aware of certain complications that can be associated with their utilization. Obviously, major bleeding is a risk, but that risk seems to be low. Heparin-induced thrombocytopenia (HIT) also may occur (with both LDUH and LMWH), but the incidence is less than 1% when the prophylaxis is given for no more than 5-7 days. Any precipitous fall in the platelet count or if the platelet count drops to less than 100,000/m L, the prophylaxis should be stopped as HIT can lead to profound venous and arterial thromboembolism. (35) Care must also be taken when prophylaxis is administered in a patient with an epidural catheter as there have been reports of epidural hematoma and paralysis in such patients, although rare. In general, no epidural catheter should be placed or removed until the anticoagulant effect is minimal (usually 8-12 h after a prophylactic dose of LDUH or LMWH). Furthermore, administration of prophylactic anticoagulant should be held for at least 2 hours after catheter insertion or removal. If there is a bloody tap with catheter insertion, prophylaxis should be avoided or delayed further. (31)

Ileus

Postoperative ileus is defined as a temporary impairment of gastrointestinal mobility that occurs almost universally after major abdominal surgery. Ileus is characterized by abdominal distention, absence of bowel sounds, accumulation of gas and fluids in the bowel, and delayed passage of flatus and stool. Postoperative ileus affects all portions of the gastrointestinal tract, however, each section recovers from ileus at a different rate. The small intestine recovers first, typically within hours of surgery. The stomach usually has return of function within 24 to 48 hours. The colon takes the longest time to recover, and it may take 3 to 5 days for the colon to function normally. (36,37,38) While the majority of patients recover bowel function within 3 to 5 days, up to 25% of patients suffer from prolonged postoperative ileus. Thus, prolonged postoperative ileus contributes significantly to prolonged length of stay in the hospital following surgery as well as increased morbidity. Because of this, there is significant interest in understanding the etiologies of ileus as well as preventive and therapeutic measures to reduce its occurrence and longevity.

The pathophysiology of postoperative ileus is multifactorial. Inhibitory neural reflexes are believed to be amongst the primary causes of postoperative ileus. The parasympathetic nervous system increases intestinal motility while the sympathetic nervous system inhibits bowel function. During periods of surgical stress, sympathetic tone is significantly increased, and this results in inhibition of intestinal motility. Various studies have shown that thoracic epidural anesthesia and analgesia utilizing local anesthetics blocks these sympathetic inhibitory reflexes with a resultant decrease in the duration of postoperative ileus. (39,40,41,42) Some studies have not shown a benefit of epidural analgesia in terms of ileus, however, many of these studies utilized lumbar epidurals as well as opioid epidurals which do provide analgesia, but do not block sympathetic reflexes. In clinical practice, a combination of epidural local anesthetics in combination with an opioid is commonly utilized. This allows a lower dose of each drug to be used, thus reducing potential side effects of the local anesthetic including hypotension and motor deficits.(41) Besides benefits in terms of postoperative pain control and decreased duration of ileus, epidural analgesia is also associated with improved pulmonary function after surgery. (41)

Local bowel inflammatory responses induced by surgical trauma also contribute to the development of postoperative ileus. One recent study has demonstrated a local inflammatory response within the human muscularis propria associated with laparotomy. Specifically, there is macrophage migration to the muscularis as well as upregulation of inflammatory mediators including interleukin 6, tumor necrosis factor, inducible nitric oxide synthase, and cyclooxygenase-2.(43) Minimally invasive (i.e. laparoscopic) surgery has been demonstrated to decrease systemic inflammatory responses, and has also been associated with decreased postoperative ileus. However, the observed decreases in postoperative ileus associated with laparoscopy is likely due to a multitude of factors including decreased bowel manipulation, decreased local and systemic inflammatory responses, as well as possible bias in patient treatment such as early feeding, avoidance of nasogastric tubes, and early mobilization. (38)

For many years surgeons have utilized pharmacologic agents with known effects on bowel motility hoping to reduce the length of postoperative ileus. Two of the most commonly used agents, metoclopramide (dopamine antagonist) (44) and erythromycin (motilin receptor agonist) (45), have never been shown to reduce the length of postoperative ileus. Cisapride is the only prokinetic agent to date that has been shown to reduce the length of postoperative ileus, however, it was removed from the market due to untoward cardiovascular side effects.

Opioid analgesics are the most commonly utilized pain medications in the perioperative period. Unfortunately, these agents also contribute significantly to the duration of postoperative ileus. Endogenous opioids may also be induced as part of the stress response to surgery. Opioids have multiple adverse side effects on the gastrointestinal tract including decreased gastric motility, inhibition of small intestinal and colonic propulsive contractions, delayed oral-cecal transit, and increased fluid absorption from the bowel contents. (46) There are three main classes of opioid receptors: kappa (k ), delta (d ), and mu (m ). Central m -opioid receptors are responsible for the desired analgesic effect of opioids. These central receptors are also responsible for adverse side effects including sedation, respiratory depression, and addiction. Peripheral m -opioid receptors are responsible for the above-mentioned side effects on the gastrointestinal tract. Alvimopan (ADL 8-2698) is a peripherally acting, m -opioid receptor antagonist which has limited oral absorption and does not readily cross the blood-brain barrier due to its high molecular weight and zwitterionic structure. Thus, it is effective at blocking the adverse gastrointestinal effects of opiates without reversing analgesia or inducing withdrawal. In 2001, Taguchi et al reported a significantly earlier return of bowel function (time to passage of flatus and first bowel movement) without any adverse effects on pain control in patients randomly assigned to receive 6 mg of alvimopan beginning 2 hours before surgery and then twice daily until the first bowel movement or hospital discharge. The time to discharge was also significantly reduced from 91 to 68 hours in patients receiving 6 mg of alvimopan. (47) More recently Wolff et al, reported the results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of alvimopan (6 or 12 mg) in the management of patients undergoing surgery. A total of 510 patients were randomized to receive 6 mg alvimopan, 12 mg alvimopan, or placebo 2 hours before surgery and then twice a day until discharge or for up to 7 days. More than 95% of the patients underwent bowel surgery and the remainder underwent radical hysterectomy. In this study, patients taking alvimopan experienced a significantly decreased length of postoperative ileus as defined as return of bowel function as well as intake of solid food. In the 12 mg alvimopan group, length of hospital stay was also significantly decreased. All of the groups required similar overall doses of opioids for pain control. Patients in the placebo group experienced more nausea and vomiting while patients in the 12 mg alvimopan group required nasogastric tube insertion significantly less than the patients in the placebo group (4.8% vs 14.8%). (48)

It has been realized for quite some time that the routine use of nasogastric tubes after abdominal surgery has no effect on the duration of postoperative ileus and that the majority of patients will not require the insertion of a nasogastric tube for nausea and vomiting in the perioperative period. Certainly, there are patients who will benefit from decompression, but this can rarely be predicted at the time surgery. Therefore, the routine use of prophylactic nasogastric tubes is no longer recommended. With the advent of laparoscopic colon surgery and the faster recovery associated with these operations, surgeons have also been more aggressive in terms of pushing for early mobilization of the patient, early feeding of the patient before the return of bowel function, expeditious removal of Foley catheters, etc. and patients tolerate these interventions very well. These same principles are also being applied to patients undergoing open colorectal surgery with similar encouraging results in terms of patient tolerance, resolution of postoperative ileus, and decreased length of stay without an increase in postoperative complications or readmissions to the hospital. (49, 50, 51, 52) Utilizing these accelerated care plans, many patients undergoing open colonic surgery are having lengths of stay that match laparoscopic lengths of stay. (53) Other novel interventions that have been shown to reduce the duration of postoperative ileus include gum chewing (54) and mechanical massage of the abdominal wall (55).

Conclusion

The perioperative management of the colorectal surgical patient requires thoughtful consideration of associated comorbidities that may contribute to perioperative morbidity and mortality. Utilization of risk management strategies allows the surgeon to adequately assess risks as well as to implement treatments that will decrease morbidity both perioperatively and in the long term. Perioperative beta-blockade should be considered in all patients at risk for cardiac complications. Thromboembolic prophylaxis must be utilized in all colorectal surgical patients undergoing abdominal and pelvic surgery as this population of patients is at a minimum at high risk for such complications. Strategies should also be utilized to attempt to decrease the duration of postoperative ileus. Thoracic epidural anesthesia/analgesia with local anesthetics has been associated with earlier return of bowel function and should be considered in these patients. Laparoscopic approaches should be utilized whenever possible as patients have less pain, decreased duration of ileus, and earlier return to normal activities. Lessons learned from laparoscopic surgery should also be used in our postoperative management. Namely, early mobilization and early feeding protocols should be considered in all patients, including those undergoing open surgery. All of these strategies should be utilized together with the goals of reducing perioperative morbidity, duration of ileus, length of hospital stay, and overall costs.

References

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