Cleveland Clinic Journal of Medicine

Diabetes confers an increased risk of perioperative morbidity and mortality, mostly from infection and cardiovascular events. It is not unusual for surgical patients with diabetes to have a number of comorbidities or underlying chronic vascular complications that put them at risk for cardiovascular events or an infectious complication. Silent ischemia, coronary artery disease, and autonomic neuropathy are common among patients with diabetes, and each can contribute to perioperative morbidity and mortality. These are important considerations since nearly one-fifth of surgical patients have diabetes and since a person with diabetes has a 50% risk of undergoing surgery at some point in his or her lifetime.¹

This article reviews the preoperative evaluation of patients with diabetes, discusses the relation between glycemic control and perioperative outcomes, and examines targets and strategies for glycemic control in patients with type 1 and type 2 diabetes throughout the perioperative period.

PREOPERATIVE EVALUATION

The preoperative evaluation must consider first and foremost the status of the patient’s diabetes and his or her surgical risk factors. Also important are the characteristics of the procedure to be performed, the method of anesthesia to be used, and select laboratory values.

Diabetes status

The type of diabetes and its treatment must be considered. Type 1 diabetes requires continuous insulin therapy to prevent ketoacidosis; patients with type 2 diabetes are usually treated with oral medications with or without insulin. Baseline control of blood glucose is a predictor of morbidity following surgery. Hypoglycemia is associated with increased morbidity in the inpatient setting, so a history of severe hypoglycemic events or of difficulty recognizing hypoglycemia (hypoglycemia unawareness) should be elicited in the preoperative evaluation. Complications of diabetes and other comorbidities also must be evaluated, along with their treatments.

Surgical risk factors

Patients with diabetes have surgical risk factors specific to their health—namely, cardiovascular risk factors that may or may not have been previously diagnosed. Patients with diabetes may have silent ischemia, atypical manifestations of coronary ischemia, or underlying cardiomyopathy. Many patients with type 2 diabetes have hypertension, which may complicate perioperative management. Other common surgical risk factors in this population include obesity, chronic kidney disease, and undiagnosed autonomic dysfunction, which may compromise hemodynamic stability in the perioperative period. Additionally, patients with long-standing diabetes experience reductions in pulmonary function (eg, forced expiratory volume, peak expiratory flow, and diffusion capacity for carbon monoxide) related to disease duration and vascular injury,² which may complicate weaning from ventilatory support.

Characteristics of the procedure and anesthetic

Both surgery and anesthesia may induce an increase in levels of stress hormones (epinephrine, cortisol, growth hormone) and inflammatory cytokines (interleukin-6 and tumor necrosis factor–alpha), resulting in insulin resistance and impaired insulin secretion (even among patients who present with adequate insulin secretion). These in turn contribute to lipolysis and protein catabolism, leading to hyperglycemia and, if a patient is severely insulin deficient, ketoacidosis. Other factors that particularly affect insulin resistance and secretion include cardiovascular bypass surgery, sepsis, the need for total parenteral nutrition, and steroid therapy.

The characteristics of the surgical procedure, including the type of surgery as well as its urgency, duration, and timing (morning vs later in the day), are important in planning for perioperative glycemic management. For example, a short, minor procedure may require only observation, whereas more extensive procedures warrant periodic monitoring and active glycemic management with insulin infusions.

The type of anesthesia should also be considered. Compared with epidural anesthesia, general anesthesia is associated with greater stimulation of the sympathetic nervous system and increased catecholamine levels, resulting in more pronounced hyperglycemia.³

Preoperative tests

Preoperative testing and laboratory evaluation should include, at minimum, an electrocardiogram, a basic metabolic panel to assess renal function, electrolyte levels, and hemoglobin A_1c measurement. For low-risk procedures in patients with adequate exercise tolerance, no diagnostic tests might be needed. In any case, knowledge of the hemoglobin A_1c level may help not only to classify perioperative risk but also to determine postoperative care, including the choice of antiglycemic medications at discharge.

IMPORTANCE OF GLYCEMIC CONTROL

Preoperative glycemic control has a significant impact on the risk of infectious complications—including pneumonia, wound infection, urinary tract infection, and sepsis—in patients with diabetes across a variety of surgical procedures.⁴ Similarly, postoperative glycemic control—to a mean blood glucose level less than 200 mg/dL in the immediate postoperative period—significantly reduces the incidence of deep sternal wound infection after open heart surgery.⁵

Among patients undergoing cardiothoracic surgery, both cardiac-related and overall mortality are greater with increasing postoperative blood glucose levels, although a cause-and-effect relationship has not been established.⁶

Glycemic control matters regardless of diabetes status

Hyperglycemia affects mortality regardless of diabetes status. In a study of 779 consecutive patients admitted for acute myocardial infarction, mortality at 180 days was highly associated with hyperglycemia on admission independent of a history of diabetes; the highest mortality was among hyperglycemic patients without previously known diabetes.⁷ Similarly, a large study of glycemic control in intensive care unit (ICU) patients receiving insulin found that mortality in nondiabetic patients increased with median glucose level and was higher than mortality in diabetic patients.⁸ These findings suggest a need for vigilance in the perioperative and critical care management of all patients with hyperglycemia, regardless of preadmission diabetes diagnosis, as they carry significant morbidity and mortality risk.

GLYCEMIC CONTROL IN THE CRITICALLY ILL: SOME SUPPORT FOR A MODIFIED TARGET, BUT VIGILANCE FOR HYPOGLYCEMIA NEEDED

The landmark study by Van den Berghe et al of intensive insulin therapy in surgical ICU patients demonstrated significant reductions in morbidity and mortality when glucose levels were controlled aggressively (80 to 110 mg/dL; average, 103 mg/dL) compared with conventional control (180 to 200 mg/dL).⁹ The benefit of intensive glycemic control was evident on outcomes such as the occurrence of sepsis, need for dialysis, need for blood transfusion, and development of acute polyneuropathy. Intensive insulin therapy was also associated with cost savings compared with conventional insulin therapy in mechanically ventilated patients.¹⁰

However, a number of subsequent studies have clearly shown that as blood glucose levels approach normoglycemia, the risks of hypoglycemia, especially severe hypoglycemia, can offset the benefits of tight blood glucose control.

A follow-up study by Ven den Berghe et al in a medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation, and earlier discharge from the ICU and hospital.¹¹

The recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to a target blood glucose of 81 to 108 mg/dL (intensive group) or 180 mg/dL or less (control group).¹² At study’s end, the groups’ mean blood glucose levels were 115 mg/dL and 144 mg/dL, respectively, while rates of severe hypoglycemia (blood glucose < 40 mg/dL) were 6.8% and 0.5%, respectively. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), driven by severe hypoglycemic events. Notably, blood glucose monitoring in this and other studies was conducted at a frequency of anywhere between 1 and 4 hours.

The conclusions of the available data would support, for the time being, a modified glycemic target in critically ill patients, with strict avoidance of severe hypoglycemia. The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if blood glucose levels exceed 180 mg/dL, with target glucose levels less than 180 mg/dL in critically ill patients and less than 140 mg/dL in non–critically ill patients.¹³ Development and implementation of safer insulin infusion algorithms and more frequent and accurate blood glucose monitoring in this setting should enable us to achieve better glycemic targets with lower risk.

In hospitalized patients with hyperglycemia, three different components of insulin replacement require management¹:

Basal insulin replacement consists of a long-acting insulin preparation administered regardless of the patient’s oral intake status, with the premise of matching hepatic (endogenous) glucose production

Prandial insulin replacement requires a rapid-acting insulin preparation given to cover nutritional needs

Supplemental (or correction) insulin replacement requires a rapid-acting preparation (usually the same insulin type as for prandial coverage) to correct blood glucose values that exceed predetermined glycemic targets.

For most patients, basal insulin replacement might be appropriate preoperatively to control fasting glucose, whereas during surgery, especially if prolonged or high risk, an intravenous (IV) insulin drip is the most effective means of glucose control. The postoperative transition from the IV insulin drip usually involves basal insulin replacement plus supplemental rapid-acting insulin. Prandial or nutritional insulin should be started once the patient begins to receive nutrition (oral, enteral, or hyperalimentation).

GOALS OF PERIOPERATIVE GLYCEMIC CONTROL

Perioperative glycemic management has several key objectives:

• Avoidance of clinically significant hyper- or hypoglycemia
• Maintenance of electrolyte and fluid balance
• Prevention of ketoacidosis, which is imperative in patients with type 1 diabetes, who require insulin at all times
• Achievement of specific glycemic targets, as discussed above—ie, less than 180 mg/dL in critically ill patients and less than 140 mg/dL in stable patients.¹³

Strategies differ across the perioperative timeline

Strategies for perioperative glycemic control differ before, during, and after surgery, as summarized immediately below and detailed in the following sections.

Preoperatively, glycemia should be stabilized, typically with subcutaneous insulin, if there is enough time to do so. For patients who have not previously been on insulin, placing them on an insulin supplemental scale to correct glycemia to desired targets might be a first step. In the setting of hyperglycemia, these patients may also be started on a low dose of basal insulin, with preference given to basal insulin analogs, given their consistent and relatively peakless action profile and lower risk of hypoglycemia. A starting dose of 0.2 to 0.4 U/kg is appropriate and carries a low risk of hypoglycemia. For patients already using insulin on an outpatient basis, continuing their basal insulin dose, possibly at a reduced dosage (25% less), together with supplemental-scale insulin coverage, should stabilize blood glucose levels. For patients on combination insulin or premixed insulin types, the basal insulin dose for preoperative management can be estimated by taking the patient’s usual total daily dose and delivering 40% to 50% of that dose as a basal insulin analog injection. Clearly, a supplemental scale should be implemented along with basal insulin replacement.

Intraoperatively, switching to IV insulin may be appropriate for stabilizing glycemia, depending on the type of surgery. A number of IV insulin protocols have been proposed, although no consistent comparisons of efficacy or safety among these protocols have been published.

Postoperatively, patients eventually should be transitioned from IV to subcutaneous insulin when glycemic control stabilizes. This transition may be complicated for many reasons. Oral intake may be inconsistent. The surgery and surrounding environment can induce stressors, promote susceptibility to infection, and increase insulin resistance. Additionally, some patients may be on hyperalimentation. Specific instructions for the transition from IV to subcutaneous insulin are covered later in this article.

PREOPERATIVE GLYCEMIC MANAGEMENT

In patients with type 2 diabetes, oral agents pose certain safety risks and should be discontinued prior to surgery.

Sulfonylureas may induce hypoglycemia in patients who are placed on NPO (“nothing by mouth”) orders and should be held in patients who are fasting.

Metformin can induce lactic acidosis if kidney function declines and should be withheld 1 to 2 days before planned surgery if a need for IV contrast is anticipated or the procedure could potentially lead to hemodynamic instability and reduced renal perfusion.

Thiazolidinediones may cause fluid retention that can complicate the postoperative period; they can be discontinued several days prior to a planned surgery.

GLP-1 agonists, such as exenatide, can slow gastric motility and potentially delay gastrointestinal recovery after major surgery; they should be held the day of surgery.

DPP-4 inhibitors (incretin enhancers), such as sitagliptin, do not have significant side effects and, if need be, can be continued. Because incretin therapies act via a glucose-dependent mechanism, they are unlikely to cause hypoglycemia, even in a patient whose oral intake is held or delayed. On the other hand, since their effect is mostly in reducing postprandial glycemia, there may be little need to use them in a patient who is NPO.

Patients with type 1 diabetes must continue basal insulin replacement preoperatively (0.2 to 0.3 U/kg/day of a long-acting insulin). Patients with type 2 diabetes may benefit from basal insulin replacement, as previously noted.

Supplemental insulin scales are used to correct hyper­glycemia regardless of a patient’s oral intake status. They can be individualized based on the estimated total daily insulin dose and require glycemic targets to be established. Fingerstick glucose monitoring should be done every 4 to 6 hours in a patient who is NPO, and supplemental-scale insulin should be used to correct glucose values that exceed target. For supplemental-scale coverage, rapid-acting insulin analogs have a shorter duration of action than human regular insulin and may be given subcutaneously every 4 to 6 hours, whereas regular insulin should not be given more often than every 6 hours to correct hyperglycemia. These differences in action duration should be kept in mind to minimize the potential for insulin stacking.

INTRAOPERATIVE GLYCEMIC MANAGEMENT

Procedure length is an important determinant

Strategies for intraoperative glucose management vary according to the length of the procedure.

For minor, short procedures, the preoperative glucose management orders may be continued.

For longer, more complex procedures, a switch to an IV insulin drip is safe and allows rapid adjustments in dosing and plasma glucose levels. Ideally, IV insulin is started prior to the procedure so that the glucose level is stable once the patient arrives in the operating room. Given the logistics of IV insulin management, including the need for frequent monitoring (hourly) and dose adjustments, this type of treatment should be reserved for environments with adequate numbers of trained staff.

IV regular insulin is therapy of choice

Adapted, with permission, from Diabetes Care (Goldberg PA, et al. Diabetes Care 2004; 27:461–467), Copyright © 2004 by the American Diabetes Association.

Several different algorithms for IV regular insulin therapy are in use. Some are static, such as those of Markovitz et al¹⁴ and Stockton et al,¹⁵ while others are dynamic (ie, doses are self-adjusted based on changes in blood glucose level), such as the “Yale protocol” of Goldberg et al (Figure 1).¹⁶

Start subcutaneous transition before stopping IV drip

Transitioning from IV to subcutaneous insulin is often complicated. Nonoral nutrition options (ie, parenteral nutrition or enteral supplementation) must be considered. As noted, insulin must be replaced according to physiologic needs, which requires that a long-acting basal insulin be used regardless of oral intake status, a rapid-acting insulin be given to cover prandial or nutritional needs, and supplemental rapid-acting insulin be used to correct hyperglycemia.

In the transition from IV insulin, basal insulin replacement can begin at any time. I recommend starting the transition from IV to subcutaneous insulin about 12 to 24 hours before discontinuing the insulin drip. In type 1 diabetes, this transition ensures basal insulin coverage and minimizes the risk of developing ketones and ketoacidosis. In type 2 diabetes, it can ensure a more stable transition and better glycemic control.

Determining the basal insulin dose

Switching to subcutaneous supplemental insulin

Instructions must be given for switching to subcutaneous supplemental doses of insulin. Glycemic targets, generally from less than 130 to 150 mg/dL, must be established, as must the frequency of fingerstick testing:

• If the patient is being fed enterally or parenterally, fingerstick testing is recommended every 4 to 6 hours if a rapid-acting insulin analog is used and every 6 hours if regular insulin is used.
• If the patient is eating, fingerstick testing should be performed before meals and at bedtime.

Covering nutritional requirements

Nutrition-related insulin needs depend on the type of caloric intake prescribed:

In patients receiving total parenteral nutrition (TPN), start 1 U of regular insulin (placed in the bag) for every 10 to 15 g of dextrose in the TPN mixture.

In patients receiving enteral nutrition, use regular insulin every 6 hours or a rapid-acting insulin analog every 4 hours. Start 1 U of insulin subcutaneously for every 10 to 15 g of delivered carbohydrates. For example, if a patient is receiving 10 g of carbohydrates per hour, a rapid-acting analog given at a dose of 4 U every 4 hours (1 U per 10 g of carbohydrates) should adequately cover enteral feedings. For any bolus feedings, give the injection as a full bolus 15 to 20 minutes in advance, based on the carbohydrate content of the feeding.

In patients who are eating, use regular insulin or a rapid-acting insulin analog before meals. Again, start 1 U of insulin subcutaneously for every 10 to 15 g of carbohydrates, or use the prandial portion of the Miami 4/12 rule (Figure 2). For example, in a 60-kg patient one would start with 5 U (60 ÷ 12) of a rapid-acting insulin before each meal.

Basal/bolus replacement outperforms supplemental-scale regular insulin

Use of a basal/bolus insulin regimen appears to be more beneficial than supplemental-scale regular insulin in hospitalized patients with type 2 diabetes, according to a recent randomized trial comparing the two approaches in 130 such patients with blood glucose levels greater than 140 mg/dL.¹⁷ In the group randomized to basal/bolus insulin, the starting total daily dose was 0.4 to 0.5 U/kg/day, with half the dose given as basal insulin (insulin glargine) once daily and half given as a rapid-acting insulin analog (glulisine) in fixed doses before every meal. A rapid-acting analog was used for supplemental insulin in the basal/bolus regimen. By study’s end, patients in the basal/bolus group were receiving a higher total daily insulin dose than those in the supplemental-scale group (mean of 42 U/day vs 13 U/day).

Mean daily blood glucose levels were 27 mg/dL lower, on average, in patients who received basal/bolus therapy compared with the supplemental-scale group, yet there was no difference between groups in the risk of hypoglycemia. More patients randomized to basal/bolus therapy achieved the glycemic goal of less than 140 mg/dL (66% vs 38%). Fourteen percent of patients assigned to supplemental-scale insulin had values persistently greater than 240 mg/dL and had to be switched to the basal/bolus regimen.¹⁷

SUMMARY

Perioperative glycemic control can reduce morbidity, particularly the incidence of infectious complications, in surgical patients, even in those without diagnosed diabetes. Optimal management of glycemia in the perioperative period involves applying principles of physiologic insulin replacement. Postoperatively, the transition from IV to subcutaneous insulin can be achieved through the use of basal insulin for coverage of fasting insulin needs, regardless of the patient’s feeding status, and the use of rapid-acting insulin to cover hyperglycemia and nutritional needs. Management of hospitalized patients exclusively with supplemental-scale regular insulin should be abandoned.

Question from the audience: As an attending physician in a preoperative clinic I’m never sure what to do with NPH insulin the morning of surgery. What guidance can you give?

Dr. Meneghini: NPH is a peaking basal insulin, and the peak can induce hypoglycemia in a patient who is NPO. If we have the opportunity, we try to switch patients previously receiving insulin therapy to a long-acting basal insulin analog, which has a much flatter action profile and is safer in the fasting state. If there is no opportunity for switching, we instruct the patient to take two-thirds of his or her usual morning dose of insulin and we initiate a D5 drip when the patient arrives at the hospital.

Question from the audience: How do you handle perioperative insulin in patients on insulin pumps?

Dr. Meneghini: The pumps provide a subcutaneous basal insulin infusion, which should, if set correctly, maintain stable blood glucose levels when the patient is NPO. Supplemental doses of insulin to correct hyperglycemia can be delivered via the usual subcutaneous practice with a syringe or insulin pen. If you are uncomfortable with pump function, or if the pump insertion site interferes with the surgery site, simply replace the 24-hour basal amount delivered via pump with an injection of glargine or detemir divided into twice-daily injections. Correct hyperglycemia with supplemental-scale insulin as per usual protocol.

Question from the audience: The manufacturer of insulin glargine makes no recommendations for its use the night before or morning of surgery. What do you recommend?

Dr. Meneghini: It depends on whether the glargine is dosed appropriately. Most patients with type 2 diabetes require 0.4 to 0.6 U/kg/day of a long-acting insulin. If they’re on much more, they may be overdosed, and I would cut the basal dose by about half. Otherwise, 75% to 100% of the usual basal amount is appropriate. In type 1 diabetes, the usual replacement dose of basal insulin is 0.2 to 0.3 U/kg/day. If a patient is in this range, the basal insulin can be continued. Patients who experience hypoglycemia, or a substantial fall in blood glucose if meals are skipped or delayed, may be getting too much basal insulin and might benefit from a dose reduction when placed on NPO status.

Question from the audience: Metformin has a black-box warning advising that it be stopped at least 48 hours before surgery, but patients often come to surgery having taken metformin within the prior 12 to 24 hours. How should we manage such patients coming for elective surgery?

Dr. Meneghini: Metformin is cleared exclusively by the kidneys; its accumulation as a result of impaired kidney function (eg, due to hemodynamic instability or radiology studies using IV iodine) can result in increased lactic acid production by the liver and lactic acidosis. A patient who has taken metformin within the prior 48 hours but doesn’t have a risk of hemodynamic dysfunction is at low risk of lactic acidosis if hydrated appropriately. There’s not much choice if a patient needs urgent surgery and has recently taken metformin; in that case, just ensure maintenance of adequate glomerular filtration via fluid repletion to clear the drug.

Question from the audience: What’s the evidence for tight glycemic control or any type of glycemic control in patients undergoing outpatient surgery or “same-day” patients who will be admitted to a regular surgical floor? Also, what would you consider maximal glucose values for a patient going into elective surgery?

Dr. Meneghini: I haven’t seen any guidelines for glycemic control in patients undergoing outpatient surgery. If a patient has poor glycemic control coming into surgery, even for a minor procedure, the risk of an infectious complication may be increased. Keeping blood glucose below 180 mg/dL and avoiding electrolyte imbalances is likely sufficient in such patients. On the second question, if it’s an elective procedure and can be delayed a few hours, you can certainly institute IV insulin therapy to correct hyperglycemia rapidly—just ensure adequate replacement of fluids since the patient may have had volume depletion or dehydration as a result of the preceding osmotic diuresis. Once glycemic control is improved (blood glucose < 180–200 mg/dL), the patient can proceed to surgery.

Question from the audience: What are your recommendations for resuming oral diabetes medications after surgery?

Dr. Meneghini: Once patients are tolerating their meals and being considered for discharge, you may want to resume their oral medications, assuming their admission hemoglobin A_1c levels were near goal. If glycemic control was inadequate preoperatively, this may be a good opportunity to adjust their prior regimen to more appropriate therapy. In some cases, this might include some form of insulin, either basal therapy or basal and supplemental insulin.

Diabetes confers an increased risk of perioperative morbidity and mortality, mostly from infection and cardiovascular events. It is not unusual for surgical patients with diabetes to have a number of comorbidities or underlying chronic vascular complications that put them at risk for cardiovascular events or an infectious complication. Silent ischemia, coronary artery disease, and autonomic neuropathy are common among patients with diabetes, and each can contribute to perioperative morbidity and mortality. These are important considerations since nearly one-fifth of surgical patients have diabetes and since a person with diabetes has a 50% risk of undergoing surgery at some point in his or her lifetime.¹

This article reviews the preoperative evaluation of patients with diabetes, discusses the relation between glycemic control and perioperative outcomes, and examines targets and strategies for glycemic control in patients with type 1 and type 2 diabetes throughout the perioperative period.

PREOPERATIVE EVALUATION

The preoperative evaluation must consider first and foremost the status of the patient’s diabetes and his or her surgical risk factors. Also important are the characteristics of the procedure to be performed, the method of anesthesia to be used, and select laboratory values.

Diabetes status

The type of diabetes and its treatment must be considered. Type 1 diabetes requires continuous insulin therapy to prevent ketoacidosis; patients with type 2 diabetes are usually treated with oral medications with or without insulin. Baseline control of blood glucose is a predictor of morbidity following surgery. Hypoglycemia is associated with increased morbidity in the inpatient setting, so a history of severe hypoglycemic events or of difficulty recognizing hypoglycemia (hypoglycemia unawareness) should be elicited in the preoperative evaluation. Complications of diabetes and other comorbidities also must be evaluated, along with their treatments.

Surgical risk factors

Patients with diabetes have surgical risk factors specific to their health—namely, cardiovascular risk factors that may or may not have been previously diagnosed. Patients with diabetes may have silent ischemia, atypical manifestations of coronary ischemia, or underlying cardiomyopathy. Many patients with type 2 diabetes have hypertension, which may complicate perioperative management. Other common surgical risk factors in this population include obesity, chronic kidney disease, and undiagnosed autonomic dysfunction, which may compromise hemodynamic stability in the perioperative period. Additionally, patients with long-standing diabetes experience reductions in pulmonary function (eg, forced expiratory volume, peak expiratory flow, and diffusion capacity for carbon monoxide) related to disease duration and vascular injury,² which may complicate weaning from ventilatory support.

Characteristics of the procedure and anesthetic

Both surgery and anesthesia may induce an increase in levels of stress hormones (epinephrine, cortisol, growth hormone) and inflammatory cytokines (interleukin-6 and tumor necrosis factor–alpha), resulting in insulin resistance and impaired insulin secretion (even among patients who present with adequate insulin secretion). These in turn contribute to lipolysis and protein catabolism, leading to hyperglycemia and, if a patient is severely insulin deficient, ketoacidosis. Other factors that particularly affect insulin resistance and secretion include cardiovascular bypass surgery, sepsis, the need for total parenteral nutrition, and steroid therapy.

The characteristics of the surgical procedure, including the type of surgery as well as its urgency, duration, and timing (morning vs later in the day), are important in planning for perioperative glycemic management. For example, a short, minor procedure may require only observation, whereas more extensive procedures warrant periodic monitoring and active glycemic management with insulin infusions.

The type of anesthesia should also be considered. Compared with epidural anesthesia, general anesthesia is associated with greater stimulation of the sympathetic nervous system and increased catecholamine levels, resulting in more pronounced hyperglycemia.³

Preoperative tests

Preoperative testing and laboratory evaluation should include, at minimum, an electrocardiogram, a basic metabolic panel to assess renal function, electrolyte levels, and hemoglobin A_1c measurement. For low-risk procedures in patients with adequate exercise tolerance, no diagnostic tests might be needed. In any case, knowledge of the hemoglobin A_1c level may help not only to classify perioperative risk but also to determine postoperative care, including the choice of antiglycemic medications at discharge.

IMPORTANCE OF GLYCEMIC CONTROL

Preoperative glycemic control has a significant impact on the risk of infectious complications—including pneumonia, wound infection, urinary tract infection, and sepsis—in patients with diabetes across a variety of surgical procedures.⁴ Similarly, postoperative glycemic control—to a mean blood glucose level less than 200 mg/dL in the immediate postoperative period—significantly reduces the incidence of deep sternal wound infection after open heart surgery.⁵

Among patients undergoing cardiothoracic surgery, both cardiac-related and overall mortality are greater with increasing postoperative blood glucose levels, although a cause-and-effect relationship has not been established.⁶

Glycemic control matters regardless of diabetes status

Hyperglycemia affects mortality regardless of diabetes status. In a study of 779 consecutive patients admitted for acute myocardial infarction, mortality at 180 days was highly associated with hyperglycemia on admission independent of a history of diabetes; the highest mortality was among hyperglycemic patients without previously known diabetes.⁷ Similarly, a large study of glycemic control in intensive care unit (ICU) patients receiving insulin found that mortality in nondiabetic patients increased with median glucose level and was higher than mortality in diabetic patients.⁸ These findings suggest a need for vigilance in the perioperative and critical care management of all patients with hyperglycemia, regardless of preadmission diabetes diagnosis, as they carry significant morbidity and mortality risk.

GLYCEMIC CONTROL IN THE CRITICALLY ILL: SOME SUPPORT FOR A MODIFIED TARGET, BUT VIGILANCE FOR HYPOGLYCEMIA NEEDED

The landmark study by Van den Berghe et al of intensive insulin therapy in surgical ICU patients demonstrated significant reductions in morbidity and mortality when glucose levels were controlled aggressively (80 to 110 mg/dL; average, 103 mg/dL) compared with conventional control (180 to 200 mg/dL).⁹ The benefit of intensive glycemic control was evident on outcomes such as the occurrence of sepsis, need for dialysis, need for blood transfusion, and development of acute polyneuropathy. Intensive insulin therapy was also associated with cost savings compared with conventional insulin therapy in mechanically ventilated patients.¹⁰

However, a number of subsequent studies have clearly shown that as blood glucose levels approach normoglycemia, the risks of hypoglycemia, especially severe hypoglycemia, can offset the benefits of tight blood glucose control.

A follow-up study by Ven den Berghe et al in a medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation, and earlier discharge from the ICU and hospital.¹¹

The recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to a target blood glucose of 81 to 108 mg/dL (intensive group) or 180 mg/dL or less (control group).¹² At study’s end, the groups’ mean blood glucose levels were 115 mg/dL and 144 mg/dL, respectively, while rates of severe hypoglycemia (blood glucose < 40 mg/dL) were 6.8% and 0.5%, respectively. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), driven by severe hypoglycemic events. Notably, blood glucose monitoring in this and other studies was conducted at a frequency of anywhere between 1 and 4 hours.

The conclusions of the available data would support, for the time being, a modified glycemic target in critically ill patients, with strict avoidance of severe hypoglycemia. The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if blood glucose levels exceed 180 mg/dL, with target glucose levels less than 180 mg/dL in critically ill patients and less than 140 mg/dL in non–critically ill patients.¹³ Development and implementation of safer insulin infusion algorithms and more frequent and accurate blood glucose monitoring in this setting should enable us to achieve better glycemic targets with lower risk.

In hospitalized patients with hyperglycemia, three different components of insulin replacement require management¹:

Basal insulin replacement consists of a long-acting insulin preparation administered regardless of the patient’s oral intake status, with the premise of matching hepatic (endogenous) glucose production

Prandial insulin replacement requires a rapid-acting insulin preparation given to cover nutritional needs

Supplemental (or correction) insulin replacement requires a rapid-acting preparation (usually the same insulin type as for prandial coverage) to correct blood glucose values that exceed predetermined glycemic targets.

For most patients, basal insulin replacement might be appropriate preoperatively to control fasting glucose, whereas during surgery, especially if prolonged or high risk, an intravenous (IV) insulin drip is the most effective means of glucose control. The postoperative transition from the IV insulin drip usually involves basal insulin replacement plus supplemental rapid-acting insulin. Prandial or nutritional insulin should be started once the patient begins to receive nutrition (oral, enteral, or hyperalimentation).

GOALS OF PERIOPERATIVE GLYCEMIC CONTROL

Perioperative glycemic management has several key objectives:

• Avoidance of clinically significant hyper- or hypoglycemia
• Maintenance of electrolyte and fluid balance
• Prevention of ketoacidosis, which is imperative in patients with type 1 diabetes, who require insulin at all times
• Achievement of specific glycemic targets, as discussed above—ie, less than 180 mg/dL in critically ill patients and less than 140 mg/dL in stable patients.¹³

Strategies differ across the perioperative timeline

Strategies for perioperative glycemic control differ before, during, and after surgery, as summarized immediately below and detailed in the following sections.

Preoperatively, glycemia should be stabilized, typically with subcutaneous insulin, if there is enough time to do so. For patients who have not previously been on insulin, placing them on an insulin supplemental scale to correct glycemia to desired targets might be a first step. In the setting of hyperglycemia, these patients may also be started on a low dose of basal insulin, with preference given to basal insulin analogs, given their consistent and relatively peakless action profile and lower risk of hypoglycemia. A starting dose of 0.2 to 0.4 U/kg is appropriate and carries a low risk of hypoglycemia. For patients already using insulin on an outpatient basis, continuing their basal insulin dose, possibly at a reduced dosage (25% less), together with supplemental-scale insulin coverage, should stabilize blood glucose levels. For patients on combination insulin or premixed insulin types, the basal insulin dose for preoperative management can be estimated by taking the patient’s usual total daily dose and delivering 40% to 50% of that dose as a basal insulin analog injection. Clearly, a supplemental scale should be implemented along with basal insulin replacement.

Intraoperatively, switching to IV insulin may be appropriate for stabilizing glycemia, depending on the type of surgery. A number of IV insulin protocols have been proposed, although no consistent comparisons of efficacy or safety among these protocols have been published.

Postoperatively, patients eventually should be transitioned from IV to subcutaneous insulin when glycemic control stabilizes. This transition may be complicated for many reasons. Oral intake may be inconsistent. The surgery and surrounding environment can induce stressors, promote susceptibility to infection, and increase insulin resistance. Additionally, some patients may be on hyperalimentation. Specific instructions for the transition from IV to subcutaneous insulin are covered later in this article.

PREOPERATIVE GLYCEMIC MANAGEMENT

In patients with type 2 diabetes, oral agents pose certain safety risks and should be discontinued prior to surgery.

Sulfonylureas may induce hypoglycemia in patients who are placed on NPO (“nothing by mouth”) orders and should be held in patients who are fasting.

Metformin can induce lactic acidosis if kidney function declines and should be withheld 1 to 2 days before planned surgery if a need for IV contrast is anticipated or the procedure could potentially lead to hemodynamic instability and reduced renal perfusion.

Thiazolidinediones may cause fluid retention that can complicate the postoperative period; they can be discontinued several days prior to a planned surgery.

GLP-1 agonists, such as exenatide, can slow gastric motility and potentially delay gastrointestinal recovery after major surgery; they should be held the day of surgery.

DPP-4 inhibitors (incretin enhancers), such as sitagliptin, do not have significant side effects and, if need be, can be continued. Because incretin therapies act via a glucose-dependent mechanism, they are unlikely to cause hypoglycemia, even in a patient whose oral intake is held or delayed. On the other hand, since their effect is mostly in reducing postprandial glycemia, there may be little need to use them in a patient who is NPO.

Patients with type 1 diabetes must continue basal insulin replacement preoperatively (0.2 to 0.3 U/kg/day of a long-acting insulin). Patients with type 2 diabetes may benefit from basal insulin replacement, as previously noted.

Supplemental insulin scales are used to correct hyper­glycemia regardless of a patient’s oral intake status. They can be individualized based on the estimated total daily insulin dose and require glycemic targets to be established. Fingerstick glucose monitoring should be done every 4 to 6 hours in a patient who is NPO, and supplemental-scale insulin should be used to correct glucose values that exceed target. For supplemental-scale coverage, rapid-acting insulin analogs have a shorter duration of action than human regular insulin and may be given subcutaneously every 4 to 6 hours, whereas regular insulin should not be given more often than every 6 hours to correct hyperglycemia. These differences in action duration should be kept in mind to minimize the potential for insulin stacking.

INTRAOPERATIVE GLYCEMIC MANAGEMENT

Procedure length is an important determinant

Strategies for intraoperative glucose management vary according to the length of the procedure.

For minor, short procedures, the preoperative glucose management orders may be continued.

For longer, more complex procedures, a switch to an IV insulin drip is safe and allows rapid adjustments in dosing and plasma glucose levels. Ideally, IV insulin is started prior to the procedure so that the glucose level is stable once the patient arrives in the operating room. Given the logistics of IV insulin management, including the need for frequent monitoring (hourly) and dose adjustments, this type of treatment should be reserved for environments with adequate numbers of trained staff.

IV regular insulin is therapy of choice

Adapted, with permission, from Diabetes Care (Goldberg PA, et al. Diabetes Care 2004; 27:461–467), Copyright © 2004 by the American Diabetes Association.

Several different algorithms for IV regular insulin therapy are in use. Some are static, such as those of Markovitz et al¹⁴ and Stockton et al,¹⁵ while others are dynamic (ie, doses are self-adjusted based on changes in blood glucose level), such as the “Yale protocol” of Goldberg et al (Figure 1).¹⁶

Start subcutaneous transition before stopping IV drip

Transitioning from IV to subcutaneous insulin is often complicated. Nonoral nutrition options (ie, parenteral nutrition or enteral supplementation) must be considered. As noted, insulin must be replaced according to physiologic needs, which requires that a long-acting basal insulin be used regardless of oral intake status, a rapid-acting insulin be given to cover prandial or nutritional needs, and supplemental rapid-acting insulin be used to correct hyperglycemia.

In the transition from IV insulin, basal insulin replacement can begin at any time. I recommend starting the transition from IV to subcutaneous insulin about 12 to 24 hours before discontinuing the insulin drip. In type 1 diabetes, this transition ensures basal insulin coverage and minimizes the risk of developing ketones and ketoacidosis. In type 2 diabetes, it can ensure a more stable transition and better glycemic control.

Determining the basal insulin dose

Switching to subcutaneous supplemental insulin

Instructions must be given for switching to subcutaneous supplemental doses of insulin. Glycemic targets, generally from less than 130 to 150 mg/dL, must be established, as must the frequency of fingerstick testing:

• If the patient is being fed enterally or parenterally, fingerstick testing is recommended every 4 to 6 hours if a rapid-acting insulin analog is used and every 6 hours if regular insulin is used.
• If the patient is eating, fingerstick testing should be performed before meals and at bedtime.

Covering nutritional requirements

Nutrition-related insulin needs depend on the type of caloric intake prescribed:

In patients receiving total parenteral nutrition (TPN), start 1 U of regular insulin (placed in the bag) for every 10 to 15 g of dextrose in the TPN mixture.

In patients receiving enteral nutrition, use regular insulin every 6 hours or a rapid-acting insulin analog every 4 hours. Start 1 U of insulin subcutaneously for every 10 to 15 g of delivered carbohydrates. For example, if a patient is receiving 10 g of carbohydrates per hour, a rapid-acting analog given at a dose of 4 U every 4 hours (1 U per 10 g of carbohydrates) should adequately cover enteral feedings. For any bolus feedings, give the injection as a full bolus 15 to 20 minutes in advance, based on the carbohydrate content of the feeding.

In patients who are eating, use regular insulin or a rapid-acting insulin analog before meals. Again, start 1 U of insulin subcutaneously for every 10 to 15 g of carbohydrates, or use the prandial portion of the Miami 4/12 rule (Figure 2). For example, in a 60-kg patient one would start with 5 U (60 ÷ 12) of a rapid-acting insulin before each meal.

Basal/bolus replacement outperforms supplemental-scale regular insulin

Use of a basal/bolus insulin regimen appears to be more beneficial than supplemental-scale regular insulin in hospitalized patients with type 2 diabetes, according to a recent randomized trial comparing the two approaches in 130 such patients with blood glucose levels greater than 140 mg/dL.¹⁷ In the group randomized to basal/bolus insulin, the starting total daily dose was 0.4 to 0.5 U/kg/day, with half the dose given as basal insulin (insulin glargine) once daily and half given as a rapid-acting insulin analog (glulisine) in fixed doses before every meal. A rapid-acting analog was used for supplemental insulin in the basal/bolus regimen. By study’s end, patients in the basal/bolus group were receiving a higher total daily insulin dose than those in the supplemental-scale group (mean of 42 U/day vs 13 U/day).

Mean daily blood glucose levels were 27 mg/dL lower, on average, in patients who received basal/bolus therapy compared with the supplemental-scale group, yet there was no difference between groups in the risk of hypoglycemia. More patients randomized to basal/bolus therapy achieved the glycemic goal of less than 140 mg/dL (66% vs 38%). Fourteen percent of patients assigned to supplemental-scale insulin had values persistently greater than 240 mg/dL and had to be switched to the basal/bolus regimen.¹⁷

SUMMARY

Perioperative glycemic control can reduce morbidity, particularly the incidence of infectious complications, in surgical patients, even in those without diagnosed diabetes. Optimal management of glycemia in the perioperative period involves applying principles of physiologic insulin replacement. Postoperatively, the transition from IV to subcutaneous insulin can be achieved through the use of basal insulin for coverage of fasting insulin needs, regardless of the patient’s feeding status, and the use of rapid-acting insulin to cover hyperglycemia and nutritional needs. Management of hospitalized patients exclusively with supplemental-scale regular insulin should be abandoned.

Question from the audience: As an attending physician in a preoperative clinic I’m never sure what to do with NPH insulin the morning of surgery. What guidance can you give?

Dr. Meneghini: NPH is a peaking basal insulin, and the peak can induce hypoglycemia in a patient who is NPO. If we have the opportunity, we try to switch patients previously receiving insulin therapy to a long-acting basal insulin analog, which has a much flatter action profile and is safer in the fasting state. If there is no opportunity for switching, we instruct the patient to take two-thirds of his or her usual morning dose of insulin and we initiate a D5 drip when the patient arrives at the hospital.

Question from the audience: How do you handle perioperative insulin in patients on insulin pumps?

Dr. Meneghini: The pumps provide a subcutaneous basal insulin infusion, which should, if set correctly, maintain stable blood glucose levels when the patient is NPO. Supplemental doses of insulin to correct hyperglycemia can be delivered via the usual subcutaneous practice with a syringe or insulin pen. If you are uncomfortable with pump function, or if the pump insertion site interferes with the surgery site, simply replace the 24-hour basal amount delivered via pump with an injection of glargine or detemir divided into twice-daily injections. Correct hyperglycemia with supplemental-scale insulin as per usual protocol.

Question from the audience: The manufacturer of insulin glargine makes no recommendations for its use the night before or morning of surgery. What do you recommend?

Dr. Meneghini: It depends on whether the glargine is dosed appropriately. Most patients with type 2 diabetes require 0.4 to 0.6 U/kg/day of a long-acting insulin. If they’re on much more, they may be overdosed, and I would cut the basal dose by about half. Otherwise, 75% to 100% of the usual basal amount is appropriate. In type 1 diabetes, the usual replacement dose of basal insulin is 0.2 to 0.3 U/kg/day. If a patient is in this range, the basal insulin can be continued. Patients who experience hypoglycemia, or a substantial fall in blood glucose if meals are skipped or delayed, may be getting too much basal insulin and might benefit from a dose reduction when placed on NPO status.

Question from the audience: Metformin has a black-box warning advising that it be stopped at least 48 hours before surgery, but patients often come to surgery having taken metformin within the prior 12 to 24 hours. How should we manage such patients coming for elective surgery?

Dr. Meneghini: Metformin is cleared exclusively by the kidneys; its accumulation as a result of impaired kidney function (eg, due to hemodynamic instability or radiology studies using IV iodine) can result in increased lactic acid production by the liver and lactic acidosis. A patient who has taken metformin within the prior 48 hours but doesn’t have a risk of hemodynamic dysfunction is at low risk of lactic acidosis if hydrated appropriately. There’s not much choice if a patient needs urgent surgery and has recently taken metformin; in that case, just ensure maintenance of adequate glomerular filtration via fluid repletion to clear the drug.

Question from the audience: What’s the evidence for tight glycemic control or any type of glycemic control in patients undergoing outpatient surgery or “same-day” patients who will be admitted to a regular surgical floor? Also, what would you consider maximal glucose values for a patient going into elective surgery?

Dr. Meneghini: I haven’t seen any guidelines for glycemic control in patients undergoing outpatient surgery. If a patient has poor glycemic control coming into surgery, even for a minor procedure, the risk of an infectious complication may be increased. Keeping blood glucose below 180 mg/dL and avoiding electrolyte imbalances is likely sufficient in such patients. On the second question, if it’s an elective procedure and can be delayed a few hours, you can certainly institute IV insulin therapy to correct hyperglycemia rapidly—just ensure adequate replacement of fluids since the patient may have had volume depletion or dehydration as a result of the preceding osmotic diuresis. Once glycemic control is improved (blood glucose < 180–200 mg/dL), the patient can proceed to surgery.

Question from the audience: What are your recommendations for resuming oral diabetes medications after surgery?

Dr. Meneghini: Once patients are tolerating their meals and being considered for discharge, you may want to resume their oral medications, assuming their admission hemoglobin A_1c levels were near goal. If glycemic control was inadequate preoperatively, this may be a good opportunity to adjust their prior regimen to more appropriate therapy. In some cases, this might include some form of insulin, either basal therapy or basal and supplemental insulin.

Diabetes confers an increased risk of perioperative morbidity and mortality, mostly from infection and cardiovascular events. It is not unusual for surgical patients with diabetes to have a number of comorbidities or underlying chronic vascular complications that put them at risk for cardiovascular events or an infectious complication. Silent ischemia, coronary artery disease, and autonomic neuropathy are common among patients with diabetes, and each can contribute to perioperative morbidity and mortality. These are important considerations since nearly one-fifth of surgical patients have diabetes and since a person with diabetes has a 50% risk of undergoing surgery at some point in his or her lifetime.¹

This article reviews the preoperative evaluation of patients with diabetes, discusses the relation between glycemic control and perioperative outcomes, and examines targets and strategies for glycemic control in patients with type 1 and type 2 diabetes throughout the perioperative period.

PREOPERATIVE EVALUATION

The preoperative evaluation must consider first and foremost the status of the patient’s diabetes and his or her surgical risk factors. Also important are the characteristics of the procedure to be performed, the method of anesthesia to be used, and select laboratory values.

Diabetes status

The type of diabetes and its treatment must be considered. Type 1 diabetes requires continuous insulin therapy to prevent ketoacidosis; patients with type 2 diabetes are usually treated with oral medications with or without insulin. Baseline control of blood glucose is a predictor of morbidity following surgery. Hypoglycemia is associated with increased morbidity in the inpatient setting, so a history of severe hypoglycemic events or of difficulty recognizing hypoglycemia (hypoglycemia unawareness) should be elicited in the preoperative evaluation. Complications of diabetes and other comorbidities also must be evaluated, along with their treatments.

Surgical risk factors

Patients with diabetes have surgical risk factors specific to their health—namely, cardiovascular risk factors that may or may not have been previously diagnosed. Patients with diabetes may have silent ischemia, atypical manifestations of coronary ischemia, or underlying cardiomyopathy. Many patients with type 2 diabetes have hypertension, which may complicate perioperative management. Other common surgical risk factors in this population include obesity, chronic kidney disease, and undiagnosed autonomic dysfunction, which may compromise hemodynamic stability in the perioperative period. Additionally, patients with long-standing diabetes experience reductions in pulmonary function (eg, forced expiratory volume, peak expiratory flow, and diffusion capacity for carbon monoxide) related to disease duration and vascular injury,² which may complicate weaning from ventilatory support.

Characteristics of the procedure and anesthetic

Both surgery and anesthesia may induce an increase in levels of stress hormones (epinephrine, cortisol, growth hormone) and inflammatory cytokines (interleukin-6 and tumor necrosis factor–alpha), resulting in insulin resistance and impaired insulin secretion (even among patients who present with adequate insulin secretion). These in turn contribute to lipolysis and protein catabolism, leading to hyperglycemia and, if a patient is severely insulin deficient, ketoacidosis. Other factors that particularly affect insulin resistance and secretion include cardiovascular bypass surgery, sepsis, the need for total parenteral nutrition, and steroid therapy.

The characteristics of the surgical procedure, including the type of surgery as well as its urgency, duration, and timing (morning vs later in the day), are important in planning for perioperative glycemic management. For example, a short, minor procedure may require only observation, whereas more extensive procedures warrant periodic monitoring and active glycemic management with insulin infusions.

The type of anesthesia should also be considered. Compared with epidural anesthesia, general anesthesia is associated with greater stimulation of the sympathetic nervous system and increased catecholamine levels, resulting in more pronounced hyperglycemia.³

Preoperative tests

Preoperative testing and laboratory evaluation should include, at minimum, an electrocardiogram, a basic metabolic panel to assess renal function, electrolyte levels, and hemoglobin A_1c measurement. For low-risk procedures in patients with adequate exercise tolerance, no diagnostic tests might be needed. In any case, knowledge of the hemoglobin A_1c level may help not only to classify perioperative risk but also to determine postoperative care, including the choice of antiglycemic medications at discharge.

IMPORTANCE OF GLYCEMIC CONTROL

Preoperative glycemic control has a significant impact on the risk of infectious complications—including pneumonia, wound infection, urinary tract infection, and sepsis—in patients with diabetes across a variety of surgical procedures.⁴ Similarly, postoperative glycemic control—to a mean blood glucose level less than 200 mg/dL in the immediate postoperative period—significantly reduces the incidence of deep sternal wound infection after open heart surgery.⁵

Among patients undergoing cardiothoracic surgery, both cardiac-related and overall mortality are greater with increasing postoperative blood glucose levels, although a cause-and-effect relationship has not been established.⁶

Glycemic control matters regardless of diabetes status

Hyperglycemia affects mortality regardless of diabetes status. In a study of 779 consecutive patients admitted for acute myocardial infarction, mortality at 180 days was highly associated with hyperglycemia on admission independent of a history of diabetes; the highest mortality was among hyperglycemic patients without previously known diabetes.⁷ Similarly, a large study of glycemic control in intensive care unit (ICU) patients receiving insulin found that mortality in nondiabetic patients increased with median glucose level and was higher than mortality in diabetic patients.⁸ These findings suggest a need for vigilance in the perioperative and critical care management of all patients with hyperglycemia, regardless of preadmission diabetes diagnosis, as they carry significant morbidity and mortality risk.

GLYCEMIC CONTROL IN THE CRITICALLY ILL: SOME SUPPORT FOR A MODIFIED TARGET, BUT VIGILANCE FOR HYPOGLYCEMIA NEEDED

The landmark study by Van den Berghe et al of intensive insulin therapy in surgical ICU patients demonstrated significant reductions in morbidity and mortality when glucose levels were controlled aggressively (80 to 110 mg/dL; average, 103 mg/dL) compared with conventional control (180 to 200 mg/dL).⁹ The benefit of intensive glycemic control was evident on outcomes such as the occurrence of sepsis, need for dialysis, need for blood transfusion, and development of acute polyneuropathy. Intensive insulin therapy was also associated with cost savings compared with conventional insulin therapy in mechanically ventilated patients.¹⁰

However, a number of subsequent studies have clearly shown that as blood glucose levels approach normoglycemia, the risks of hypoglycemia, especially severe hypoglycemia, can offset the benefits of tight blood glucose control.

A follow-up study by Ven den Berghe et al in a medical ICU failed to show a mortality benefit from tight glycemic control, though patients in the intensive control arm experienced less renal injury, faster weaning from ventilation, and earlier discharge from the ICU and hospital.¹¹

The recent NICE-SUGAR study of aggressive glucose control in the ICU randomized patients to a target blood glucose of 81 to 108 mg/dL (intensive group) or 180 mg/dL or less (control group).¹² At study’s end, the groups’ mean blood glucose levels were 115 mg/dL and 144 mg/dL, respectively, while rates of severe hypoglycemia (blood glucose < 40 mg/dL) were 6.8% and 0.5%, respectively. Mortality rates were higher in the intensive therapy group (27.5%) than in the control group (24.9%), driven by severe hypoglycemic events. Notably, blood glucose monitoring in this and other studies was conducted at a frequency of anywhere between 1 and 4 hours.

The conclusions of the available data would support, for the time being, a modified glycemic target in critically ill patients, with strict avoidance of severe hypoglycemia. The recent consensus statement from the American Association of Clinical Endocrinologists and the American Diabetes Association recommends using insulin therapy if blood glucose levels exceed 180 mg/dL, with target glucose levels less than 180 mg/dL in critically ill patients and less than 140 mg/dL in non–critically ill patients.¹³ Development and implementation of safer insulin infusion algorithms and more frequent and accurate blood glucose monitoring in this setting should enable us to achieve better glycemic targets with lower risk.

In hospitalized patients with hyperglycemia, three different components of insulin replacement require management¹:

Basal insulin replacement consists of a long-acting insulin preparation administered regardless of the patient’s oral intake status, with the premise of matching hepatic (endogenous) glucose production

Prandial insulin replacement requires a rapid-acting insulin preparation given to cover nutritional needs

Supplemental (or correction) insulin replacement requires a rapid-acting preparation (usually the same insulin type as for prandial coverage) to correct blood glucose values that exceed predetermined glycemic targets.

For most patients, basal insulin replacement might be appropriate preoperatively to control fasting glucose, whereas during surgery, especially if prolonged or high risk, an intravenous (IV) insulin drip is the most effective means of glucose control. The postoperative transition from the IV insulin drip usually involves basal insulin replacement plus supplemental rapid-acting insulin. Prandial or nutritional insulin should be started once the patient begins to receive nutrition (oral, enteral, or hyperalimentation).

GOALS OF PERIOPERATIVE GLYCEMIC CONTROL

Perioperative glycemic management has several key objectives:

• Avoidance of clinically significant hyper- or hypoglycemia
• Maintenance of electrolyte and fluid balance
• Prevention of ketoacidosis, which is imperative in patients with type 1 diabetes, who require insulin at all times
• Achievement of specific glycemic targets, as discussed above—ie, less than 180 mg/dL in critically ill patients and less than 140 mg/dL in stable patients.¹³

Strategies differ across the perioperative timeline

Strategies for perioperative glycemic control differ before, during, and after surgery, as summarized immediately below and detailed in the following sections.

Preoperatively, glycemia should be stabilized, typically with subcutaneous insulin, if there is enough time to do so. For patients who have not previously been on insulin, placing them on an insulin supplemental scale to correct glycemia to desired targets might be a first step. In the setting of hyperglycemia, these patients may also be started on a low dose of basal insulin, with preference given to basal insulin analogs, given their consistent and relatively peakless action profile and lower risk of hypoglycemia. A starting dose of 0.2 to 0.4 U/kg is appropriate and carries a low risk of hypoglycemia. For patients already using insulin on an outpatient basis, continuing their basal insulin dose, possibly at a reduced dosage (25% less), together with supplemental-scale insulin coverage, should stabilize blood glucose levels. For patients on combination insulin or premixed insulin types, the basal insulin dose for preoperative management can be estimated by taking the patient’s usual total daily dose and delivering 40% to 50% of that dose as a basal insulin analog injection. Clearly, a supplemental scale should be implemented along with basal insulin replacement.

Intraoperatively, switching to IV insulin may be appropriate for stabilizing glycemia, depending on the type of surgery. A number of IV insulin protocols have been proposed, although no consistent comparisons of efficacy or safety among these protocols have been published.

Postoperatively, patients eventually should be transitioned from IV to subcutaneous insulin when glycemic control stabilizes. This transition may be complicated for many reasons. Oral intake may be inconsistent. The surgery and surrounding environment can induce stressors, promote susceptibility to infection, and increase insulin resistance. Additionally, some patients may be on hyperalimentation. Specific instructions for the transition from IV to subcutaneous insulin are covered later in this article.

PREOPERATIVE GLYCEMIC MANAGEMENT

In patients with type 2 diabetes, oral agents pose certain safety risks and should be discontinued prior to surgery.

Sulfonylureas may induce hypoglycemia in patients who are placed on NPO (“nothing by mouth”) orders and should be held in patients who are fasting.

Metformin can induce lactic acidosis if kidney function declines and should be withheld 1 to 2 days before planned surgery if a need for IV contrast is anticipated or the procedure could potentially lead to hemodynamic instability and reduced renal perfusion.

Thiazolidinediones may cause fluid retention that can complicate the postoperative period; they can be discontinued several days prior to a planned surgery.

GLP-1 agonists, such as exenatide, can slow gastric motility and potentially delay gastrointestinal recovery after major surgery; they should be held the day of surgery.

DPP-4 inhibitors (incretin enhancers), such as sitagliptin, do not have significant side effects and, if need be, can be continued. Because incretin therapies act via a glucose-dependent mechanism, they are unlikely to cause hypoglycemia, even in a patient whose oral intake is held or delayed. On the other hand, since their effect is mostly in reducing postprandial glycemia, there may be little need to use them in a patient who is NPO.

Patients with type 1 diabetes must continue basal insulin replacement preoperatively (0.2 to 0.3 U/kg/day of a long-acting insulin). Patients with type 2 diabetes may benefit from basal insulin replacement, as previously noted.

Supplemental insulin scales are used to correct hyper­glycemia regardless of a patient’s oral intake status. They can be individualized based on the estimated total daily insulin dose and require glycemic targets to be established. Fingerstick glucose monitoring should be done every 4 to 6 hours in a patient who is NPO, and supplemental-scale insulin should be used to correct glucose values that exceed target. For supplemental-scale coverage, rapid-acting insulin analogs have a shorter duration of action than human regular insulin and may be given subcutaneously every 4 to 6 hours, whereas regular insulin should not be given more often than every 6 hours to correct hyperglycemia. These differences in action duration should be kept in mind to minimize the potential for insulin stacking.

INTRAOPERATIVE GLYCEMIC MANAGEMENT

Procedure length is an important determinant

Strategies for intraoperative glucose management vary according to the length of the procedure.

For minor, short procedures, the preoperative glucose management orders may be continued.

For longer, more complex procedures, a switch to an IV insulin drip is safe and allows rapid adjustments in dosing and plasma glucose levels. Ideally, IV insulin is started prior to the procedure so that the glucose level is stable once the patient arrives in the operating room. Given the logistics of IV insulin management, including the need for frequent monitoring (hourly) and dose adjustments, this type of treatment should be reserved for environments with adequate numbers of trained staff.

IV regular insulin is therapy of choice

Adapted, with permission, from Diabetes Care (Goldberg PA, et al. Diabetes Care 2004; 27:461–467), Copyright © 2004 by the American Diabetes Association.

Several different algorithms for IV regular insulin therapy are in use. Some are static, such as those of Markovitz et al¹⁴ and Stockton et al,¹⁵ while others are dynamic (ie, doses are self-adjusted based on changes in blood glucose level), such as the “Yale protocol” of Goldberg et al (Figure 1).¹⁶

Start subcutaneous transition before stopping IV drip

Transitioning from IV to subcutaneous insulin is often complicated. Nonoral nutrition options (ie, parenteral nutrition or enteral supplementation) must be considered. As noted, insulin must be replaced according to physiologic needs, which requires that a long-acting basal insulin be used regardless of oral intake status, a rapid-acting insulin be given to cover prandial or nutritional needs, and supplemental rapid-acting insulin be used to correct hyperglycemia.

In the transition from IV insulin, basal insulin replacement can begin at any time. I recommend starting the transition from IV to subcutaneous insulin about 12 to 24 hours before discontinuing the insulin drip. In type 1 diabetes, this transition ensures basal insulin coverage and minimizes the risk of developing ketones and ketoacidosis. In type 2 diabetes, it can ensure a more stable transition and better glycemic control.

Determining the basal insulin dose

Switching to subcutaneous supplemental insulin

Instructions must be given for switching to subcutaneous supplemental doses of insulin. Glycemic targets, generally from less than 130 to 150 mg/dL, must be established, as must the frequency of fingerstick testing:

• If the patient is being fed enterally or parenterally, fingerstick testing is recommended every 4 to 6 hours if a rapid-acting insulin analog is used and every 6 hours if regular insulin is used.
• If the patient is eating, fingerstick testing should be performed before meals and at bedtime.

Covering nutritional requirements

Nutrition-related insulin needs depend on the type of caloric intake prescribed:

In patients receiving total parenteral nutrition (TPN), start 1 U of regular insulin (placed in the bag) for every 10 to 15 g of dextrose in the TPN mixture.

In patients receiving enteral nutrition, use regular insulin every 6 hours or a rapid-acting insulin analog every 4 hours. Start 1 U of insulin subcutaneously for every 10 to 15 g of delivered carbohydrates. For example, if a patient is receiving 10 g of carbohydrates per hour, a rapid-acting analog given at a dose of 4 U every 4 hours (1 U per 10 g of carbohydrates) should adequately cover enteral feedings. For any bolus feedings, give the injection as a full bolus 15 to 20 minutes in advance, based on the carbohydrate content of the feeding.

In patients who are eating, use regular insulin or a rapid-acting insulin analog before meals. Again, start 1 U of insulin subcutaneously for every 10 to 15 g of carbohydrates, or use the prandial portion of the Miami 4/12 rule (Figure 2). For example, in a 60-kg patient one would start with 5 U (60 ÷ 12) of a rapid-acting insulin before each meal.

Basal/bolus replacement outperforms supplemental-scale regular insulin

Use of a basal/bolus insulin regimen appears to be more beneficial than supplemental-scale regular insulin in hospitalized patients with type 2 diabetes, according to a recent randomized trial comparing the two approaches in 130 such patients with blood glucose levels greater than 140 mg/dL.¹⁷ In the group randomized to basal/bolus insulin, the starting total daily dose was 0.4 to 0.5 U/kg/day, with half the dose given as basal insulin (insulin glargine) once daily and half given as a rapid-acting insulin analog (glulisine) in fixed doses before every meal. A rapid-acting analog was used for supplemental insulin in the basal/bolus regimen. By study’s end, patients in the basal/bolus group were receiving a higher total daily insulin dose than those in the supplemental-scale group (mean of 42 U/day vs 13 U/day).

Mean daily blood glucose levels were 27 mg/dL lower, on average, in patients who received basal/bolus therapy compared with the supplemental-scale group, yet there was no difference between groups in the risk of hypoglycemia. More patients randomized to basal/bolus therapy achieved the glycemic goal of less than 140 mg/dL (66% vs 38%). Fourteen percent of patients assigned to supplemental-scale insulin had values persistently greater than 240 mg/dL and had to be switched to the basal/bolus regimen.¹⁷

SUMMARY

Perioperative glycemic control can reduce morbidity, particularly the incidence of infectious complications, in surgical patients, even in those without diagnosed diabetes. Optimal management of glycemia in the perioperative period involves applying principles of physiologic insulin replacement. Postoperatively, the transition from IV to subcutaneous insulin can be achieved through the use of basal insulin for coverage of fasting insulin needs, regardless of the patient’s feeding status, and the use of rapid-acting insulin to cover hyperglycemia and nutritional needs. Management of hospitalized patients exclusively with supplemental-scale regular insulin should be abandoned.

Question from the audience: As an attending physician in a preoperative clinic I’m never sure what to do with NPH insulin the morning of surgery. What guidance can you give?

Dr. Meneghini: NPH is a peaking basal insulin, and the peak can induce hypoglycemia in a patient who is NPO. If we have the opportunity, we try to switch patients previously receiving insulin therapy to a long-acting basal insulin analog, which has a much flatter action profile and is safer in the fasting state. If there is no opportunity for switching, we instruct the patient to take two-thirds of his or her usual morning dose of insulin and we initiate a D5 drip when the patient arrives at the hospital.

Question from the audience: How do you handle perioperative insulin in patients on insulin pumps?

Dr. Meneghini: The pumps provide a subcutaneous basal insulin infusion, which should, if set correctly, maintain stable blood glucose levels when the patient is NPO. Supplemental doses of insulin to correct hyperglycemia can be delivered via the usual subcutaneous practice with a syringe or insulin pen. If you are uncomfortable with pump function, or if the pump insertion site interferes with the surgery site, simply replace the 24-hour basal amount delivered via pump with an injection of glargine or detemir divided into twice-daily injections. Correct hyperglycemia with supplemental-scale insulin as per usual protocol.

Question from the audience: The manufacturer of insulin glargine makes no recommendations for its use the night before or morning of surgery. What do you recommend?

Dr. Meneghini: It depends on whether the glargine is dosed appropriately. Most patients with type 2 diabetes require 0.4 to 0.6 U/kg/day of a long-acting insulin. If they’re on much more, they may be overdosed, and I would cut the basal dose by about half. Otherwise, 75% to 100% of the usual basal amount is appropriate. In type 1 diabetes, the usual replacement dose of basal insulin is 0.2 to 0.3 U/kg/day. If a patient is in this range, the basal insulin can be continued. Patients who experience hypoglycemia, or a substantial fall in blood glucose if meals are skipped or delayed, may be getting too much basal insulin and might benefit from a dose reduction when placed on NPO status.

Question from the audience: Metformin has a black-box warning advising that it be stopped at least 48 hours before surgery, but patients often come to surgery having taken metformin within the prior 12 to 24 hours. How should we manage such patients coming for elective surgery?

Dr. Meneghini: Metformin is cleared exclusively by the kidneys; its accumulation as a result of impaired kidney function (eg, due to hemodynamic instability or radiology studies using IV iodine) can result in increased lactic acid production by the liver and lactic acidosis. A patient who has taken metformin within the prior 48 hours but doesn’t have a risk of hemodynamic dysfunction is at low risk of lactic acidosis if hydrated appropriately. There’s not much choice if a patient needs urgent surgery and has recently taken metformin; in that case, just ensure maintenance of adequate glomerular filtration via fluid repletion to clear the drug.

Question from the audience: What’s the evidence for tight glycemic control or any type of glycemic control in patients undergoing outpatient surgery or “same-day” patients who will be admitted to a regular surgical floor? Also, what would you consider maximal glucose values for a patient going into elective surgery?

Dr. Meneghini: I haven’t seen any guidelines for glycemic control in patients undergoing outpatient surgery. If a patient has poor glycemic control coming into surgery, even for a minor procedure, the risk of an infectious complication may be increased. Keeping blood glucose below 180 mg/dL and avoiding electrolyte imbalances is likely sufficient in such patients. On the second question, if it’s an elective procedure and can be delayed a few hours, you can certainly institute IV insulin therapy to correct hyperglycemia rapidly—just ensure adequate replacement of fluids since the patient may have had volume depletion or dehydration as a result of the preceding osmotic diuresis. Once glycemic control is improved (blood glucose < 180–200 mg/dL), the patient can proceed to surgery.

Question from the audience: What are your recommendations for resuming oral diabetes medications after surgery?

Dr. Meneghini: Once patients are tolerating their meals and being considered for discharge, you may want to resume their oral medications, assuming their admission hemoglobin A_1c levels were near goal. If glycemic control was inadequate preoperatively, this may be a good opportunity to adjust their prior regimen to more appropriate therapy. In some cases, this might include some form of insulin, either basal therapy or basal and supplemental insulin.

Although pulmonary complications are not as well studied as cardiac complications in the postoperative setting, they are just as common following noncardiac surgery and are even more costly. It is worthwhile to identify surgical patients most at risk of postoperative pulmonary complications and take measures known to mitigate risk. This paper discusses important risk factors to identify during a preoperative pulmonary evaluation and then focuses on recent advances in strategies for reducing postoperative pulmonary complications. Teaching questions are included throughout, along with the rationale behind their answers.

POSTOPERATIVE PULMONARY COMPLICATIONS: WHAT ARE WE TRYING TO PREVENT AND WHY?

The definition of postoperative pulmonary complications is more variable and less intuitive than that of cardiac complications. Cardiac complications—postoperative myocardial infarction, cardiac death, and pulmonary edema—are more consistently defined and measured in clinical trials. Studies of postoperative pulmonary complications often group together pneumonia, respiratory failure, atelectasis, bronchospasm, and exacerbation of chronic obstructive pulmonary disease (COPD), making it more difficult to individually evaluate risk factors for different outcomes.

There are several reasons why it is important to consider pulmonary risk when evaluating patients preoperatively:

Pulmonary complications are as common as cardiac complications following noncardiac surgery. For example, in a secondary analysis of the cohort of noncardiac surgical patients used to validate the Revised Cardiac Risk Index,¹ Fleischmann et al found that the incidence of pulmonary complications (2.7%) was highly comparable to that of cardiac complications (2.5%).²

Respiratory failure is a marker of ill health and predicts further complications. Postoperative respiratory failure (often defined as the need for ventilation for more than 48 hours after surgery) is an extremely morbid event. Johnson et al compared the outcomes of patients with and without respiratory failure as a complication of surgery.³ Among patients with respiratory failure, 26% died within 30 days, 6% had a myocardial infarction, 35% developed pneumonia, 10% developed acute renal failure, and 3% developed a deep vein thrombosis or pulmonary embolism; in contrast, rates of each of these events were lower than 2% among patients without respiratory failure.

Pulmonary complications are expensive and require lengthy hospitalization. The National Surgical Quality Improvement Program (NSQIP) compared hospitalization costs and length of stay among patients with various postoperative complications.⁴ Among infectious, cardiovascular, venous thromboembolic, and pulmonary complications, pulmonary complications were by far the most costly and, along with venous thromboembolic complications, required the longest mean hospital stay.

For these reasons, identifying patients at risk for pulmonary complications and developing a strategy to reduce the risk is clearly worthwhile.

IDENTIFYING RISK FOR PULMONARY COMPLICATIONS

Question: Which of the following is the most important risk factor for postoperative pulmonary complications?

A. High-risk surgical site

B. General anesthesia

C. COPD

D. Obesity

The correct answer is A. Pulmonary complications differ from cardiac complications in an important way: procedure-related factors are more predictive of pulmonary complications than are patient-related factors. Even healthy patients undergoing high-risk surgery are at risk for pulmonary complications. As for the other answer choices, general anesthesia and COPD are risk factors but are not as important as surgical site, and obesity has not been shown to be a risk factor at all.

Take-home points from the 2006 ACP guideline

Patient-related risk factors. As noted in Table 1, the most important patient-related risk factors identified in the ACP guideline are increasing age and increasing American Society of Anesthesiologists (ASA) classification of comorbidity.

The effect of advanced age becomes particularly notable around age 60 years and escalates from there. This effect of age differs from that for cardiac complications, for which age drops out as a risk factor after adjustment for other diseases and risk factors. For pulmonary complications, in contrast, even older patients who are healthy are at increased risk.

The ASA classification is a general index of overall morbidity that ranges from class 1 (normal healthy patient) to class 5 (moribund patient who is not expected to survive without the operation).

Notably, COPD and smoking were only minor risk factors in the ACP analysis.

Procedure-related risk factors. Surgical site was found to be the most important of any of the patient- or procedure-related risk factors. The closer the incision is to the diaphragm, the greater the risk for pulmonary complications. Aortic, thoracic, and abdominal procedures carry the highest risk (Table 1), and among abdominal procedures, upper abdominal surgery (eg, cholecystectomy) is riskier than lower abdominal surgery (eg, gynecologic).

Other procedure-related risk factors identified were emergency surgery, surgery lasting more than 3 hours, use of general anesthesia, and multiple transfusions (Table 1).

Question: Which of the following has recently been identified as a risk factor for postoperative pulmonary complications?

A. Epidural anesthesia

B. Insulin-treated diabetes

C. Obstructive sleep apnea

D. Immobility

The correct answer is C. There is no evidence that epidural anesthesia or insulin-treated diabetes are risk factors. Immobility seems intuitively correct but has not emerged as a risk factor among high-quality studies in the literature.

Obstructive sleep apnea. The role of obstructive sleep apnea was unclear prior to publication of new data in the last couple of years. Hwang et al enrolled 172 patients who were soon to have elective surgery and had at least two of four clinical features of obstructive sleep apnea (snoring, daytime somnolence, witnessed apnea event, or crowded oropharynx).⁸ Patients underwent nocturnal oximetry before surgery and were divided into two groups based on number of desaturation episodes per hour. Patients with five or more desaturations had markedly higher rates of postoperative respiratory complications (8 complications among 98 patients) than did patients with fewer than five desaturations (1 complication among 74 patients). The presence of five or more desaturations was also associated with higher rates of cardiac, gastrointestinal, and bleeding complications. Though this was a small study, its results suggest a significant association between obstructive sleep apnea and pulmonary complications.

The issue of whether to screen patients for obstructive sleep apnea before major noncardiac surgery is still unresolved.

Pulmonary hypertension has also been identified as a risk factor in recent years with the publication of two studies that estimated its impact on morbidity and mortality after major noncardiac surgery.^9,10 One of the studies, a retrospective database review, found a 28% incidence of respiratory failure among 145 surgical patients with pulmonary hypertension.⁹ In the other study, a prospective case-control trial, respiratory failure occurred in 21% of patients with pulmonary hypertension compared with only 3% of matched controls.¹⁰ In the case-control study, pulmonary hypertension was also associated with significantly elevated rates of heart failure and in-hospital death.

The results of these studies do not support preoperative screening for undiagnosed pulmonary hypertension, but they do underscore the need to recognize established pulmonary hypertension as an important risk factor for postoperative complications.

AN UPDATED INDEX FOR RESPIRATORY FAILURE

Several years ago, investigators from the Veterans Affairs Medical Centers developed a respiratory failure index using a design similar to those of well-established indices for cardiac risk.¹¹ The same group also developed a separate risk index for pneumonia.¹²

This respiratory failure index was recently updated³ to reflect experience from private and academic hospitals, making the results more generally applicable. The researchers evaluated data from 180,000 patients undergoing major general or vascular surgery (defined according to the NSQIP) over a 3-year period. Respiratory failure was defined as requiring at least 48 hours of ventilation or unplanned reintubation.

Comparison and contrast with the ACP guideline

Question: How does the updated respiratory failure index differ most significantly from the 2006 ACP guideline?

A. New index places greater emphasis on ASA class

B. New index offers a simplified weighted point scheme

C. New index ranks low albumin as a less important risk factor

D. New index attributes low risk to cigarette use

The correct answer is C: low albumin is a minor risk factor in the respiratory failure index, whereas it was one of the single most important predictors in the ACP guideline. As for the other answer choices, the new index places about the same emphasis on ASA class and cigarette use as does the ACP guideline, and it does not offer a simplified approach, as it incorporates 28 different factors.

Overall, most risk factors were similar in the updated respiratory failure index and the ACP guideline, but the index differs in several important ways:

• The index assigns less risk to low albumin, functional dependence, and congestive heart failure
• The index assigns greater risk to orofacial surgery
• The index identifies several new risk factors—high-complexity surgery, preoperative sepsis, ascites, and hypernatremia (serum sodium > 145 mmol/L).

Postoperative CPAP: Good option when exercise ability is limited

Among the postoperative lung expansion modalities, continuous positive airway pressure (CPAP) is particularly useful for patients who are unable to perform deep breathing or incentive spirometry exercises. A recent systematic literature review identified nine randomized controlled trials of CPAP vs standard therapy in a total of 654 patients undergoing abdominal surgery.¹³ Meta-analysis of these studies showed that CPAP was associated with significant reductions in the risk of overall postoperative pulmonary complications (odds ratio [OR] = 0.66; 95% CI, 0.52–0.85), atelectasis (OR = 0.75; 95% CI, 0.58–0.97), and pneumonia (OR = 0.33; 95% CI, 0.14–0.75) relative to standard therapy.

Use nasogastric tubes selectively

Nasogastric tubes can be used either routinely following abdominal surgery or only in select patients—eg, those who have symptomatic abdominal distention or nausea. The difference is important since nasogastric tubes may potentially increase the risk of aspiration and thus lead to a pulmonary complication. Nelson et al conducted a meta-analysis of 24 studies that compared routine nasogastric tube use in abdominal surgery with selective use based on symptoms or abdominal distention.¹⁴ They found that routine use was associated with a significant increase in postoperative pulmonary complications (OR = 1.45; 95% CI, 1.08–1.93) relative to selective use, without achieving any of its intended goals.

Laparoscopic vs open surgery: Evidence begins to follow intuition

Intuitively, it seems that laparoscopic procedures should reduce risk for postoperative pulmonary complications compared with open surgical procedures, as they are associated with less postoperative pain, which should facilitate deep breathing and improve postoperative lung volumes. Nevertheless, evidence for whether laparoscopic surgery reduces the risk of pulmonary complications has been mixed until recently.

In 2008, however, Weller and Rosati published an analysis of a nationally representative database of 19,156 patients who underwent bariatric surgery in 2005.¹⁵ After adjusting for comorbidities, they found that the rate of postoperative pulmonary complications was nearly double if patients underwent open surgery as opposed to laparoscopic surgery (OR = 1.92; 95% CI, 1.54–2.38). Open surgery was also associated with significantly higher rates of sepsis, cardiovascular events, and reoperation compared with laparoscopic procedures. This study suggests that choosing laparoscopic procedures is another strategy that may reduce pulmonary complication rates, at least in the setting of bariatric surgery.

Postoperative thoracic epidural analgesia

Question: Thoracic epidural analgesia reduces rates of which of the following?

A. Pneumonia following abdominal aortic aneurysm repair

B. Pulmonary complications following coronary bypass surgery

C. Respiratory failure following abdominal surgery

D. All of the above

The correct answer is D. Thoracic epidural analgesia is another important strategy for reducing postoperative pulmonary complications, as demonstrated by a 2007 systematic literature review by Liu and Wu.¹⁶ Their analysis showed that rates of pneumonia, respiratory failure, and pulmonary complications overall were reduced by approximately one-third to more than one-half with the use of postoperative thoracic epidural analgesia in patients undergoing aortic aneurysm repair, coronary bypass surgery, and abdominal surgery.

Smoking cessation: The jury is still out

Whether preoperative cigarette cessation reduces pulmonary complication rates has been controversial over the past decade. Early reports showed that among patients who smoke, those who quit shortly before surgery actually had higher complication rates than patients who continued to smoke. The most reasonable explanation seems to be that many patients who stop smoking report increased coughing and sputum production for the first month or two. Selection bias also may have played a role in these findings.

More recently, two randomized trials studied the impact of perioperative smoking intervention programs involving counseling and nicotine replacement.^17,18 Unfortunately, both studies primarily studied patients undergoing low-risk procedures and were insufficiently powered to show a difference in  pulmonary complication rates. The question of whether smoking cessation is an effective strategy to reduce postoperative pulmonary risk remains unanswered.

Preoperative intensive lung expansion: A promising new intervention

While the effectiveness of postoperative lung expansion techniques is undisputed,⁷preoperative lung expansion—also known as inspiratory muscle training—has only recently been investigated. Hulzebos et al randomized 279 patients undergoing coronary artery bypass graft surgery who were at high risk for developing pulmonary complications to either usual care or inspiratory muscle training.¹⁹ The latter intervention involved 20 minutes per day of incentive spirometry, active breathing, and forced expiration techniques for at least 2 weeks prior to surgery. Rates of high-grade postoperative pulmonary complications were cut in half (OR = 0.52; 95% CI, 0.30–0.92) and rates of pneumonia were reduced by 60% (OR = 0.40; 95% CI, 0.19–0.84) in patients who received inspiratory muscle training relative to the usual-care group.

In clinical practice, preoperative inspiratory muscle training can be done in a chest physical therapy outpatient setting or a pulmonary rehabilitation clinic in the hospital.

There have been a number of significant recent developments in the perioperative management of pulmonary complications:

• Obstructive sleep apnea has been confirmed as a risk factor, and pulmonary hypertension has emerged as a novel risk factor.
• An updated respiratory failure index has emerged as a useful research tool to identify high-risk patients and to ensure uniform risk stratification in future research.
• Evidence has mounted for the effectiveness of several risk-reduction strategies, including the use of laparoscopic procedures for bariatric surgery; selective use of nasogastric tubes; postoperative thoracic epidural analgesia; and intensive preoperative inspiratory muscle training.

DISCUSSION

Question from the audience: I do preoperative evaluations in an orthopedic ambulatory surgery center. Our surgeons often tell me, “Just order preoperative pulmonary function tests,” or, “Get a blood gas.” How should I respond?

Dr. Smetana: This is an area of some controversy, but in general, spirometry does not add much to a preoperative risk assessment that is based on a history and physical exam. Usually if the spirometry is abnormal, it will not be a surprise after careful clinical assessment. Arterial blood gases have no role in routine preoperative assessment.

Question from the audience: A chest x-ray is often requested preoperatively, but is it a necessary study?

Dr. Smetana: The data for preoperative chest x-rays are fairly poor and don’t allow us to assess whether they accurately predict complication rates. Most studies on chest x-rays have looked at how they affect preoperative management—eg, whether they change the anesthesia or even the surgery—and have shown that preoperative management changes in only about 1% to 2% of cases. So the chest x-ray is a fairly low-yield test in this setting.

One could argue that a preoperative chest x-ray might provide a baseline for postoperative comparison, but actually it is not usually helpful in this regard. Having a baseline does not make it easier to correctly diagnose pneumonia postoperatively, for example. Abnormal chest x-rays correlate with higher risk, but most patients with abnormal films would be suspected of being at higher risk anyway based on findings from the clinical assessment.

Question from the audience: Many primary care doctors in my hospital screen patients for pulmonary hypertension, but this raises the question of what to do with any information gained. What do you tell patients? Anesthesiologists?

Dr. Smetana: I don’t recommend preoperative screening for pulmonary hypertension unless there is some specific clinical reason to look for it. We don’t know if the perioperative risks that I described for patients with diagnosed or symptomatic pulmonary hypertension would also apply to patients with unrecognized, asymptomatic pulmonary hypertension that happened to be identified by screening.

Patients with pulmonary hypertension are at very high risk, especially for respiratory failure. But we don’t have any risk-reduction strategies specific to these patients, although I would recommend applying the general risk-reduction strategies that I discussed.

Question from the audience: I saw a man at my high-risk preoperative clinic who scored normally on a 6-minute walk test but then was found sound asleep when I was ready to see him a little while later. I suspected he had undiagnosed sleep apnea, and therefore had an increased risk of postoperative pulmonary complications, but what evidence would I have to delay his surgery to diagnose the sleep apnea and stabilize him on CPAP?

Dr. Smetana: For a patient with clinically suspected but undiagnosed sleep apnea, we have some evidence that the diagnosis should be pursued before surgery is performed.⁸ If the surgery were elective, it would be appropriate to have the patient evaluated and, if obstructive sleep apnea were diagnosed, treated in the customary way with CPAP. For patients who are hospitalized after surgery, CPAP can be continued as soon as possible in the hospital.

I would not have made this recommendation a few years ago, but now the evidence is more compelling. However, at this point I would not recommend routine preoperative screening of all patients for sleep apnea. Ongoing research is looking at this question.

Follow-up question: How long should surgery be delayed to optimize the patient on CPAP?

Dr. Smetana: Risk for postoperative respiratory failure is reduced very quickly after initiating CPAP therapy. A week would probably be sufficient, but there are no good data to specifically address that question.

Question from the audience: What about patients with asthma who are undergoing surgery—which ones benefit from stress-level steroids and preoperative nebulizer therapy?

Dr. Smetana: Surprisingly, asthma—if well controlled—is not a risk factor for postoperative pulmonary complications. Patients within 80% of their predicted or personal best peak flow appear to have a risk similar to that of patients without asthma. For patients with uncontrolled or poorly controlled asthma, the general rule is the same as for patients with COPD: treat them the same as if they weren’t having surgery. If a patient with asthma has a clinical indication for cortico­steroids based on his or her condition, give cortico­steroids whether or not surgery is planned. Corticosteroids are safe and do not raise the risk of postoperative wound complications. But we have no evidence to support routine use of steroids for all patients with asthma simply because elective surgery is planned.

Follow-up question: Do you optimize poorly controlled patients with oral prednisone for several days preoperatively, or do you use a stress protocol?

Dr. Smetana: For a patient whom you would normally treat with an outpatient course of prednisone, you should do just that. For a patient with an exacerbation severe enough to require admission for intravenous steroids and inhaled nebulizer therapy, then you should use that strategy. If the surgery is elective, it should be delayed until the patient is at his or her personal best.

Although pulmonary complications are not as well studied as cardiac complications in the postoperative setting, they are just as common following noncardiac surgery and are even more costly. It is worthwhile to identify surgical patients most at risk of postoperative pulmonary complications and take measures known to mitigate risk. This paper discusses important risk factors to identify during a preoperative pulmonary evaluation and then focuses on recent advances in strategies for reducing postoperative pulmonary complications. Teaching questions are included throughout, along with the rationale behind their answers.

POSTOPERATIVE PULMONARY COMPLICATIONS: WHAT ARE WE TRYING TO PREVENT AND WHY?

The definition of postoperative pulmonary complications is more variable and less intuitive than that of cardiac complications. Cardiac complications—postoperative myocardial infarction, cardiac death, and pulmonary edema—are more consistently defined and measured in clinical trials. Studies of postoperative pulmonary complications often group together pneumonia, respiratory failure, atelectasis, bronchospasm, and exacerbation of chronic obstructive pulmonary disease (COPD), making it more difficult to individually evaluate risk factors for different outcomes.

There are several reasons why it is important to consider pulmonary risk when evaluating patients preoperatively:

Pulmonary complications are as common as cardiac complications following noncardiac surgery. For example, in a secondary analysis of the cohort of noncardiac surgical patients used to validate the Revised Cardiac Risk Index,¹ Fleischmann et al found that the incidence of pulmonary complications (2.7%) was highly comparable to that of cardiac complications (2.5%).²

Respiratory failure is a marker of ill health and predicts further complications. Postoperative respiratory failure (often defined as the need for ventilation for more than 48 hours after surgery) is an extremely morbid event. Johnson et al compared the outcomes of patients with and without respiratory failure as a complication of surgery.³ Among patients with respiratory failure, 26% died within 30 days, 6% had a myocardial infarction, 35% developed pneumonia, 10% developed acute renal failure, and 3% developed a deep vein thrombosis or pulmonary embolism; in contrast, rates of each of these events were lower than 2% among patients without respiratory failure.

Pulmonary complications are expensive and require lengthy hospitalization. The National Surgical Quality Improvement Program (NSQIP) compared hospitalization costs and length of stay among patients with various postoperative complications.⁴ Among infectious, cardiovascular, venous thromboembolic, and pulmonary complications, pulmonary complications were by far the most costly and, along with venous thromboembolic complications, required the longest mean hospital stay.

For these reasons, identifying patients at risk for pulmonary complications and developing a strategy to reduce the risk is clearly worthwhile.

IDENTIFYING RISK FOR PULMONARY COMPLICATIONS

Question: Which of the following is the most important risk factor for postoperative pulmonary complications?

A. High-risk surgical site

B. General anesthesia

C. COPD

D. Obesity

The correct answer is A. Pulmonary complications differ from cardiac complications in an important way: procedure-related factors are more predictive of pulmonary complications than are patient-related factors. Even healthy patients undergoing high-risk surgery are at risk for pulmonary complications. As for the other answer choices, general anesthesia and COPD are risk factors but are not as important as surgical site, and obesity has not been shown to be a risk factor at all.

Take-home points from the 2006 ACP guideline

Patient-related risk factors. As noted in Table 1, the most important patient-related risk factors identified in the ACP guideline are increasing age and increasing American Society of Anesthesiologists (ASA) classification of comorbidity.

The effect of advanced age becomes particularly notable around age 60 years and escalates from there. This effect of age differs from that for cardiac complications, for which age drops out as a risk factor after adjustment for other diseases and risk factors. For pulmonary complications, in contrast, even older patients who are healthy are at increased risk.

The ASA classification is a general index of overall morbidity that ranges from class 1 (normal healthy patient) to class 5 (moribund patient who is not expected to survive without the operation).

Notably, COPD and smoking were only minor risk factors in the ACP analysis.

Procedure-related risk factors. Surgical site was found to be the most important of any of the patient- or procedure-related risk factors. The closer the incision is to the diaphragm, the greater the risk for pulmonary complications. Aortic, thoracic, and abdominal procedures carry the highest risk (Table 1), and among abdominal procedures, upper abdominal surgery (eg, cholecystectomy) is riskier than lower abdominal surgery (eg, gynecologic).

Other procedure-related risk factors identified were emergency surgery, surgery lasting more than 3 hours, use of general anesthesia, and multiple transfusions (Table 1).

Question: Which of the following has recently been identified as a risk factor for postoperative pulmonary complications?

A. Epidural anesthesia

B. Insulin-treated diabetes

C. Obstructive sleep apnea

D. Immobility

The correct answer is C. There is no evidence that epidural anesthesia or insulin-treated diabetes are risk factors. Immobility seems intuitively correct but has not emerged as a risk factor among high-quality studies in the literature.

Obstructive sleep apnea. The role of obstructive sleep apnea was unclear prior to publication of new data in the last couple of years. Hwang et al enrolled 172 patients who were soon to have elective surgery and had at least two of four clinical features of obstructive sleep apnea (snoring, daytime somnolence, witnessed apnea event, or crowded oropharynx).⁸ Patients underwent nocturnal oximetry before surgery and were divided into two groups based on number of desaturation episodes per hour. Patients with five or more desaturations had markedly higher rates of postoperative respiratory complications (8 complications among 98 patients) than did patients with fewer than five desaturations (1 complication among 74 patients). The presence of five or more desaturations was also associated with higher rates of cardiac, gastrointestinal, and bleeding complications. Though this was a small study, its results suggest a significant association between obstructive sleep apnea and pulmonary complications.

The issue of whether to screen patients for obstructive sleep apnea before major noncardiac surgery is still unresolved.

Pulmonary hypertension has also been identified as a risk factor in recent years with the publication of two studies that estimated its impact on morbidity and mortality after major noncardiac surgery.^9,10 One of the studies, a retrospective database review, found a 28% incidence of respiratory failure among 145 surgical patients with pulmonary hypertension.⁹ In the other study, a prospective case-control trial, respiratory failure occurred in 21% of patients with pulmonary hypertension compared with only 3% of matched controls.¹⁰ In the case-control study, pulmonary hypertension was also associated with significantly elevated rates of heart failure and in-hospital death.

The results of these studies do not support preoperative screening for undiagnosed pulmonary hypertension, but they do underscore the need to recognize established pulmonary hypertension as an important risk factor for postoperative complications.

AN UPDATED INDEX FOR RESPIRATORY FAILURE

Several years ago, investigators from the Veterans Affairs Medical Centers developed a respiratory failure index using a design similar to those of well-established indices for cardiac risk.¹¹ The same group also developed a separate risk index for pneumonia.¹²

This respiratory failure index was recently updated³ to reflect experience from private and academic hospitals, making the results more generally applicable. The researchers evaluated data from 180,000 patients undergoing major general or vascular surgery (defined according to the NSQIP) over a 3-year period. Respiratory failure was defined as requiring at least 48 hours of ventilation or unplanned reintubation.

Comparison and contrast with the ACP guideline

Question: How does the updated respiratory failure index differ most significantly from the 2006 ACP guideline?

A. New index places greater emphasis on ASA class

B. New index offers a simplified weighted point scheme

C. New index ranks low albumin as a less important risk factor

D. New index attributes low risk to cigarette use

The correct answer is C: low albumin is a minor risk factor in the respiratory failure index, whereas it was one of the single most important predictors in the ACP guideline. As for the other answer choices, the new index places about the same emphasis on ASA class and cigarette use as does the ACP guideline, and it does not offer a simplified approach, as it incorporates 28 different factors.

Overall, most risk factors were similar in the updated respiratory failure index and the ACP guideline, but the index differs in several important ways:

• The index assigns less risk to low albumin, functional dependence, and congestive heart failure
• The index assigns greater risk to orofacial surgery
• The index identifies several new risk factors—high-complexity surgery, preoperative sepsis, ascites, and hypernatremia (serum sodium > 145 mmol/L).

Postoperative CPAP: Good option when exercise ability is limited

Among the postoperative lung expansion modalities, continuous positive airway pressure (CPAP) is particularly useful for patients who are unable to perform deep breathing or incentive spirometry exercises. A recent systematic literature review identified nine randomized controlled trials of CPAP vs standard therapy in a total of 654 patients undergoing abdominal surgery.¹³ Meta-analysis of these studies showed that CPAP was associated with significant reductions in the risk of overall postoperative pulmonary complications (odds ratio [OR] = 0.66; 95% CI, 0.52–0.85), atelectasis (OR = 0.75; 95% CI, 0.58–0.97), and pneumonia (OR = 0.33; 95% CI, 0.14–0.75) relative to standard therapy.

Use nasogastric tubes selectively

Nasogastric tubes can be used either routinely following abdominal surgery or only in select patients—eg, those who have symptomatic abdominal distention or nausea. The difference is important since nasogastric tubes may potentially increase the risk of aspiration and thus lead to a pulmonary complication. Nelson et al conducted a meta-analysis of 24 studies that compared routine nasogastric tube use in abdominal surgery with selective use based on symptoms or abdominal distention.¹⁴ They found that routine use was associated with a significant increase in postoperative pulmonary complications (OR = 1.45; 95% CI, 1.08–1.93) relative to selective use, without achieving any of its intended goals.

Laparoscopic vs open surgery: Evidence begins to follow intuition

Intuitively, it seems that laparoscopic procedures should reduce risk for postoperative pulmonary complications compared with open surgical procedures, as they are associated with less postoperative pain, which should facilitate deep breathing and improve postoperative lung volumes. Nevertheless, evidence for whether laparoscopic surgery reduces the risk of pulmonary complications has been mixed until recently.

In 2008, however, Weller and Rosati published an analysis of a nationally representative database of 19,156 patients who underwent bariatric surgery in 2005.¹⁵ After adjusting for comorbidities, they found that the rate of postoperative pulmonary complications was nearly double if patients underwent open surgery as opposed to laparoscopic surgery (OR = 1.92; 95% CI, 1.54–2.38). Open surgery was also associated with significantly higher rates of sepsis, cardiovascular events, and reoperation compared with laparoscopic procedures. This study suggests that choosing laparoscopic procedures is another strategy that may reduce pulmonary complication rates, at least in the setting of bariatric surgery.

Postoperative thoracic epidural analgesia

Question: Thoracic epidural analgesia reduces rates of which of the following?

A. Pneumonia following abdominal aortic aneurysm repair

B. Pulmonary complications following coronary bypass surgery

C. Respiratory failure following abdominal surgery

D. All of the above

The correct answer is D. Thoracic epidural analgesia is another important strategy for reducing postoperative pulmonary complications, as demonstrated by a 2007 systematic literature review by Liu and Wu.¹⁶ Their analysis showed that rates of pneumonia, respiratory failure, and pulmonary complications overall were reduced by approximately one-third to more than one-half with the use of postoperative thoracic epidural analgesia in patients undergoing aortic aneurysm repair, coronary bypass surgery, and abdominal surgery.

Smoking cessation: The jury is still out

Whether preoperative cigarette cessation reduces pulmonary complication rates has been controversial over the past decade. Early reports showed that among patients who smoke, those who quit shortly before surgery actually had higher complication rates than patients who continued to smoke. The most reasonable explanation seems to be that many patients who stop smoking report increased coughing and sputum production for the first month or two. Selection bias also may have played a role in these findings.

More recently, two randomized trials studied the impact of perioperative smoking intervention programs involving counseling and nicotine replacement.^17,18 Unfortunately, both studies primarily studied patients undergoing low-risk procedures and were insufficiently powered to show a difference in  pulmonary complication rates. The question of whether smoking cessation is an effective strategy to reduce postoperative pulmonary risk remains unanswered.

Preoperative intensive lung expansion: A promising new intervention

While the effectiveness of postoperative lung expansion techniques is undisputed,⁷preoperative lung expansion—also known as inspiratory muscle training—has only recently been investigated. Hulzebos et al randomized 279 patients undergoing coronary artery bypass graft surgery who were at high risk for developing pulmonary complications to either usual care or inspiratory muscle training.¹⁹ The latter intervention involved 20 minutes per day of incentive spirometry, active breathing, and forced expiration techniques for at least 2 weeks prior to surgery. Rates of high-grade postoperative pulmonary complications were cut in half (OR = 0.52; 95% CI, 0.30–0.92) and rates of pneumonia were reduced by 60% (OR = 0.40; 95% CI, 0.19–0.84) in patients who received inspiratory muscle training relative to the usual-care group.

In clinical practice, preoperative inspiratory muscle training can be done in a chest physical therapy outpatient setting or a pulmonary rehabilitation clinic in the hospital.

There have been a number of significant recent developments in the perioperative management of pulmonary complications:

• Obstructive sleep apnea has been confirmed as a risk factor, and pulmonary hypertension has emerged as a novel risk factor.
• An updated respiratory failure index has emerged as a useful research tool to identify high-risk patients and to ensure uniform risk stratification in future research.
• Evidence has mounted for the effectiveness of several risk-reduction strategies, including the use of laparoscopic procedures for bariatric surgery; selective use of nasogastric tubes; postoperative thoracic epidural analgesia; and intensive preoperative inspiratory muscle training.

DISCUSSION

Question from the audience: I do preoperative evaluations in an orthopedic ambulatory surgery center. Our surgeons often tell me, “Just order preoperative pulmonary function tests,” or, “Get a blood gas.” How should I respond?

Dr. Smetana: This is an area of some controversy, but in general, spirometry does not add much to a preoperative risk assessment that is based on a history and physical exam. Usually if the spirometry is abnormal, it will not be a surprise after careful clinical assessment. Arterial blood gases have no role in routine preoperative assessment.

Question from the audience: A chest x-ray is often requested preoperatively, but is it a necessary study?

Dr. Smetana: The data for preoperative chest x-rays are fairly poor and don’t allow us to assess whether they accurately predict complication rates. Most studies on chest x-rays have looked at how they affect preoperative management—eg, whether they change the anesthesia or even the surgery—and have shown that preoperative management changes in only about 1% to 2% of cases. So the chest x-ray is a fairly low-yield test in this setting.

One could argue that a preoperative chest x-ray might provide a baseline for postoperative comparison, but actually it is not usually helpful in this regard. Having a baseline does not make it easier to correctly diagnose pneumonia postoperatively, for example. Abnormal chest x-rays correlate with higher risk, but most patients with abnormal films would be suspected of being at higher risk anyway based on findings from the clinical assessment.

Question from the audience: Many primary care doctors in my hospital screen patients for pulmonary hypertension, but this raises the question of what to do with any information gained. What do you tell patients? Anesthesiologists?

Dr. Smetana: I don’t recommend preoperative screening for pulmonary hypertension unless there is some specific clinical reason to look for it. We don’t know if the perioperative risks that I described for patients with diagnosed or symptomatic pulmonary hypertension would also apply to patients with unrecognized, asymptomatic pulmonary hypertension that happened to be identified by screening.

Patients with pulmonary hypertension are at very high risk, especially for respiratory failure. But we don’t have any risk-reduction strategies specific to these patients, although I would recommend applying the general risk-reduction strategies that I discussed.

Question from the audience: I saw a man at my high-risk preoperative clinic who scored normally on a 6-minute walk test but then was found sound asleep when I was ready to see him a little while later. I suspected he had undiagnosed sleep apnea, and therefore had an increased risk of postoperative pulmonary complications, but what evidence would I have to delay his surgery to diagnose the sleep apnea and stabilize him on CPAP?

Dr. Smetana: For a patient with clinically suspected but undiagnosed sleep apnea, we have some evidence that the diagnosis should be pursued before surgery is performed.⁸ If the surgery were elective, it would be appropriate to have the patient evaluated and, if obstructive sleep apnea were diagnosed, treated in the customary way with CPAP. For patients who are hospitalized after surgery, CPAP can be continued as soon as possible in the hospital.

I would not have made this recommendation a few years ago, but now the evidence is more compelling. However, at this point I would not recommend routine preoperative screening of all patients for sleep apnea. Ongoing research is looking at this question.

Follow-up question: How long should surgery be delayed to optimize the patient on CPAP?

Dr. Smetana: Risk for postoperative respiratory failure is reduced very quickly after initiating CPAP therapy. A week would probably be sufficient, but there are no good data to specifically address that question.

Question from the audience: What about patients with asthma who are undergoing surgery—which ones benefit from stress-level steroids and preoperative nebulizer therapy?

Dr. Smetana: Surprisingly, asthma—if well controlled—is not a risk factor for postoperative pulmonary complications. Patients within 80% of their predicted or personal best peak flow appear to have a risk similar to that of patients without asthma. For patients with uncontrolled or poorly controlled asthma, the general rule is the same as for patients with COPD: treat them the same as if they weren’t having surgery. If a patient with asthma has a clinical indication for cortico­steroids based on his or her condition, give cortico­steroids whether or not surgery is planned. Corticosteroids are safe and do not raise the risk of postoperative wound complications. But we have no evidence to support routine use of steroids for all patients with asthma simply because elective surgery is planned.

Follow-up question: Do you optimize poorly controlled patients with oral prednisone for several days preoperatively, or do you use a stress protocol?

Dr. Smetana: For a patient whom you would normally treat with an outpatient course of prednisone, you should do just that. For a patient with an exacerbation severe enough to require admission for intravenous steroids and inhaled nebulizer therapy, then you should use that strategy. If the surgery is elective, it should be delayed until the patient is at his or her personal best.

Although pulmonary complications are not as well studied as cardiac complications in the postoperative setting, they are just as common following noncardiac surgery and are even more costly. It is worthwhile to identify surgical patients most at risk of postoperative pulmonary complications and take measures known to mitigate risk. This paper discusses important risk factors to identify during a preoperative pulmonary evaluation and then focuses on recent advances in strategies for reducing postoperative pulmonary complications. Teaching questions are included throughout, along with the rationale behind their answers.

POSTOPERATIVE PULMONARY COMPLICATIONS: WHAT ARE WE TRYING TO PREVENT AND WHY?

The definition of postoperative pulmonary complications is more variable and less intuitive than that of cardiac complications. Cardiac complications—postoperative myocardial infarction, cardiac death, and pulmonary edema—are more consistently defined and measured in clinical trials. Studies of postoperative pulmonary complications often group together pneumonia, respiratory failure, atelectasis, bronchospasm, and exacerbation of chronic obstructive pulmonary disease (COPD), making it more difficult to individually evaluate risk factors for different outcomes.

There are several reasons why it is important to consider pulmonary risk when evaluating patients preoperatively:

Pulmonary complications are as common as cardiac complications following noncardiac surgery. For example, in a secondary analysis of the cohort of noncardiac surgical patients used to validate the Revised Cardiac Risk Index,¹ Fleischmann et al found that the incidence of pulmonary complications (2.7%) was highly comparable to that of cardiac complications (2.5%).²

Respiratory failure is a marker of ill health and predicts further complications. Postoperative respiratory failure (often defined as the need for ventilation for more than 48 hours after surgery) is an extremely morbid event. Johnson et al compared the outcomes of patients with and without respiratory failure as a complication of surgery.³ Among patients with respiratory failure, 26% died within 30 days, 6% had a myocardial infarction, 35% developed pneumonia, 10% developed acute renal failure, and 3% developed a deep vein thrombosis or pulmonary embolism; in contrast, rates of each of these events were lower than 2% among patients without respiratory failure.

Pulmonary complications are expensive and require lengthy hospitalization. The National Surgical Quality Improvement Program (NSQIP) compared hospitalization costs and length of stay among patients with various postoperative complications.⁴ Among infectious, cardiovascular, venous thromboembolic, and pulmonary complications, pulmonary complications were by far the most costly and, along with venous thromboembolic complications, required the longest mean hospital stay.

For these reasons, identifying patients at risk for pulmonary complications and developing a strategy to reduce the risk is clearly worthwhile.

IDENTIFYING RISK FOR PULMONARY COMPLICATIONS

Question: Which of the following is the most important risk factor for postoperative pulmonary complications?

A. High-risk surgical site

B. General anesthesia

C. COPD

D. Obesity

The correct answer is A. Pulmonary complications differ from cardiac complications in an important way: procedure-related factors are more predictive of pulmonary complications than are patient-related factors. Even healthy patients undergoing high-risk surgery are at risk for pulmonary complications. As for the other answer choices, general anesthesia and COPD are risk factors but are not as important as surgical site, and obesity has not been shown to be a risk factor at all.

Take-home points from the 2006 ACP guideline

Patient-related risk factors. As noted in Table 1, the most important patient-related risk factors identified in the ACP guideline are increasing age and increasing American Society of Anesthesiologists (ASA) classification of comorbidity.

The effect of advanced age becomes particularly notable around age 60 years and escalates from there. This effect of age differs from that for cardiac complications, for which age drops out as a risk factor after adjustment for other diseases and risk factors. For pulmonary complications, in contrast, even older patients who are healthy are at increased risk.

The ASA classification is a general index of overall morbidity that ranges from class 1 (normal healthy patient) to class 5 (moribund patient who is not expected to survive without the operation).

Notably, COPD and smoking were only minor risk factors in the ACP analysis.

Procedure-related risk factors. Surgical site was found to be the most important of any of the patient- or procedure-related risk factors. The closer the incision is to the diaphragm, the greater the risk for pulmonary complications. Aortic, thoracic, and abdominal procedures carry the highest risk (Table 1), and among abdominal procedures, upper abdominal surgery (eg, cholecystectomy) is riskier than lower abdominal surgery (eg, gynecologic).

Other procedure-related risk factors identified were emergency surgery, surgery lasting more than 3 hours, use of general anesthesia, and multiple transfusions (Table 1).

Question: Which of the following has recently been identified as a risk factor for postoperative pulmonary complications?

A. Epidural anesthesia

B. Insulin-treated diabetes

C. Obstructive sleep apnea

D. Immobility

The correct answer is C. There is no evidence that epidural anesthesia or insulin-treated diabetes are risk factors. Immobility seems intuitively correct but has not emerged as a risk factor among high-quality studies in the literature.

Obstructive sleep apnea. The role of obstructive sleep apnea was unclear prior to publication of new data in the last couple of years. Hwang et al enrolled 172 patients who were soon to have elective surgery and had at least two of four clinical features of obstructive sleep apnea (snoring, daytime somnolence, witnessed apnea event, or crowded oropharynx).⁸ Patients underwent nocturnal oximetry before surgery and were divided into two groups based on number of desaturation episodes per hour. Patients with five or more desaturations had markedly higher rates of postoperative respiratory complications (8 complications among 98 patients) than did patients with fewer than five desaturations (1 complication among 74 patients). The presence of five or more desaturations was also associated with higher rates of cardiac, gastrointestinal, and bleeding complications. Though this was a small study, its results suggest a significant association between obstructive sleep apnea and pulmonary complications.

The issue of whether to screen patients for obstructive sleep apnea before major noncardiac surgery is still unresolved.

Pulmonary hypertension has also been identified as a risk factor in recent years with the publication of two studies that estimated its impact on morbidity and mortality after major noncardiac surgery.^9,10 One of the studies, a retrospective database review, found a 28% incidence of respiratory failure among 145 surgical patients with pulmonary hypertension.⁹ In the other study, a prospective case-control trial, respiratory failure occurred in 21% of patients with pulmonary hypertension compared with only 3% of matched controls.¹⁰ In the case-control study, pulmonary hypertension was also associated with significantly elevated rates of heart failure and in-hospital death.

The results of these studies do not support preoperative screening for undiagnosed pulmonary hypertension, but they do underscore the need to recognize established pulmonary hypertension as an important risk factor for postoperative complications.

AN UPDATED INDEX FOR RESPIRATORY FAILURE

Several years ago, investigators from the Veterans Affairs Medical Centers developed a respiratory failure index using a design similar to those of well-established indices for cardiac risk.¹¹ The same group also developed a separate risk index for pneumonia.¹²

This respiratory failure index was recently updated³ to reflect experience from private and academic hospitals, making the results more generally applicable. The researchers evaluated data from 180,000 patients undergoing major general or vascular surgery (defined according to the NSQIP) over a 3-year period. Respiratory failure was defined as requiring at least 48 hours of ventilation or unplanned reintubation.

Comparison and contrast with the ACP guideline

Question: How does the updated respiratory failure index differ most significantly from the 2006 ACP guideline?

A. New index places greater emphasis on ASA class

B. New index offers a simplified weighted point scheme

C. New index ranks low albumin as a less important risk factor

D. New index attributes low risk to cigarette use

The correct answer is C: low albumin is a minor risk factor in the respiratory failure index, whereas it was one of the single most important predictors in the ACP guideline. As for the other answer choices, the new index places about the same emphasis on ASA class and cigarette use as does the ACP guideline, and it does not offer a simplified approach, as it incorporates 28 different factors.

Overall, most risk factors were similar in the updated respiratory failure index and the ACP guideline, but the index differs in several important ways:

• The index assigns less risk to low albumin, functional dependence, and congestive heart failure
• The index assigns greater risk to orofacial surgery
• The index identifies several new risk factors—high-complexity surgery, preoperative sepsis, ascites, and hypernatremia (serum sodium > 145 mmol/L).

Postoperative CPAP: Good option when exercise ability is limited

Among the postoperative lung expansion modalities, continuous positive airway pressure (CPAP) is particularly useful for patients who are unable to perform deep breathing or incentive spirometry exercises. A recent systematic literature review identified nine randomized controlled trials of CPAP vs standard therapy in a total of 654 patients undergoing abdominal surgery.¹³ Meta-analysis of these studies showed that CPAP was associated with significant reductions in the risk of overall postoperative pulmonary complications (odds ratio [OR] = 0.66; 95% CI, 0.52–0.85), atelectasis (OR = 0.75; 95% CI, 0.58–0.97), and pneumonia (OR = 0.33; 95% CI, 0.14–0.75) relative to standard therapy.

Use nasogastric tubes selectively

Nasogastric tubes can be used either routinely following abdominal surgery or only in select patients—eg, those who have symptomatic abdominal distention or nausea. The difference is important since nasogastric tubes may potentially increase the risk of aspiration and thus lead to a pulmonary complication. Nelson et al conducted a meta-analysis of 24 studies that compared routine nasogastric tube use in abdominal surgery with selective use based on symptoms or abdominal distention.¹⁴ They found that routine use was associated with a significant increase in postoperative pulmonary complications (OR = 1.45; 95% CI, 1.08–1.93) relative to selective use, without achieving any of its intended goals.

Laparoscopic vs open surgery: Evidence begins to follow intuition

Intuitively, it seems that laparoscopic procedures should reduce risk for postoperative pulmonary complications compared with open surgical procedures, as they are associated with less postoperative pain, which should facilitate deep breathing and improve postoperative lung volumes. Nevertheless, evidence for whether laparoscopic surgery reduces the risk of pulmonary complications has been mixed until recently.

In 2008, however, Weller and Rosati published an analysis of a nationally representative database of 19,156 patients who underwent bariatric surgery in 2005.¹⁵ After adjusting for comorbidities, they found that the rate of postoperative pulmonary complications was nearly double if patients underwent open surgery as opposed to laparoscopic surgery (OR = 1.92; 95% CI, 1.54–2.38). Open surgery was also associated with significantly higher rates of sepsis, cardiovascular events, and reoperation compared with laparoscopic procedures. This study suggests that choosing laparoscopic procedures is another strategy that may reduce pulmonary complication rates, at least in the setting of bariatric surgery.

Postoperative thoracic epidural analgesia

Question: Thoracic epidural analgesia reduces rates of which of the following?

A. Pneumonia following abdominal aortic aneurysm repair

B. Pulmonary complications following coronary bypass surgery

C. Respiratory failure following abdominal surgery

D. All of the above

The correct answer is D. Thoracic epidural analgesia is another important strategy for reducing postoperative pulmonary complications, as demonstrated by a 2007 systematic literature review by Liu and Wu.¹⁶ Their analysis showed that rates of pneumonia, respiratory failure, and pulmonary complications overall were reduced by approximately one-third to more than one-half with the use of postoperative thoracic epidural analgesia in patients undergoing aortic aneurysm repair, coronary bypass surgery, and abdominal surgery.

Smoking cessation: The jury is still out

Whether preoperative cigarette cessation reduces pulmonary complication rates has been controversial over the past decade. Early reports showed that among patients who smoke, those who quit shortly before surgery actually had higher complication rates than patients who continued to smoke. The most reasonable explanation seems to be that many patients who stop smoking report increased coughing and sputum production for the first month or two. Selection bias also may have played a role in these findings.

More recently, two randomized trials studied the impact of perioperative smoking intervention programs involving counseling and nicotine replacement.^17,18 Unfortunately, both studies primarily studied patients undergoing low-risk procedures and were insufficiently powered to show a difference in  pulmonary complication rates. The question of whether smoking cessation is an effective strategy to reduce postoperative pulmonary risk remains unanswered.

Preoperative intensive lung expansion: A promising new intervention

While the effectiveness of postoperative lung expansion techniques is undisputed,⁷preoperative lung expansion—also known as inspiratory muscle training—has only recently been investigated. Hulzebos et al randomized 279 patients undergoing coronary artery bypass graft surgery who were at high risk for developing pulmonary complications to either usual care or inspiratory muscle training.¹⁹ The latter intervention involved 20 minutes per day of incentive spirometry, active breathing, and forced expiration techniques for at least 2 weeks prior to surgery. Rates of high-grade postoperative pulmonary complications were cut in half (OR = 0.52; 95% CI, 0.30–0.92) and rates of pneumonia were reduced by 60% (OR = 0.40; 95% CI, 0.19–0.84) in patients who received inspiratory muscle training relative to the usual-care group.

In clinical practice, preoperative inspiratory muscle training can be done in a chest physical therapy outpatient setting or a pulmonary rehabilitation clinic in the hospital.

There have been a number of significant recent developments in the perioperative management of pulmonary complications:

• Obstructive sleep apnea has been confirmed as a risk factor, and pulmonary hypertension has emerged as a novel risk factor.
• An updated respiratory failure index has emerged as a useful research tool to identify high-risk patients and to ensure uniform risk stratification in future research.
• Evidence has mounted for the effectiveness of several risk-reduction strategies, including the use of laparoscopic procedures for bariatric surgery; selective use of nasogastric tubes; postoperative thoracic epidural analgesia; and intensive preoperative inspiratory muscle training.

DISCUSSION

Question from the audience: I do preoperative evaluations in an orthopedic ambulatory surgery center. Our surgeons often tell me, “Just order preoperative pulmonary function tests,” or, “Get a blood gas.” How should I respond?

Dr. Smetana: This is an area of some controversy, but in general, spirometry does not add much to a preoperative risk assessment that is based on a history and physical exam. Usually if the spirometry is abnormal, it will not be a surprise after careful clinical assessment. Arterial blood gases have no role in routine preoperative assessment.

Question from the audience: A chest x-ray is often requested preoperatively, but is it a necessary study?

Dr. Smetana: The data for preoperative chest x-rays are fairly poor and don’t allow us to assess whether they accurately predict complication rates. Most studies on chest x-rays have looked at how they affect preoperative management—eg, whether they change the anesthesia or even the surgery—and have shown that preoperative management changes in only about 1% to 2% of cases. So the chest x-ray is a fairly low-yield test in this setting.

One could argue that a preoperative chest x-ray might provide a baseline for postoperative comparison, but actually it is not usually helpful in this regard. Having a baseline does not make it easier to correctly diagnose pneumonia postoperatively, for example. Abnormal chest x-rays correlate with higher risk, but most patients with abnormal films would be suspected of being at higher risk anyway based on findings from the clinical assessment.

Question from the audience: Many primary care doctors in my hospital screen patients for pulmonary hypertension, but this raises the question of what to do with any information gained. What do you tell patients? Anesthesiologists?

Dr. Smetana: I don’t recommend preoperative screening for pulmonary hypertension unless there is some specific clinical reason to look for it. We don’t know if the perioperative risks that I described for patients with diagnosed or symptomatic pulmonary hypertension would also apply to patients with unrecognized, asymptomatic pulmonary hypertension that happened to be identified by screening.

Patients with pulmonary hypertension are at very high risk, especially for respiratory failure. But we don’t have any risk-reduction strategies specific to these patients, although I would recommend applying the general risk-reduction strategies that I discussed.

Question from the audience: I saw a man at my high-risk preoperative clinic who scored normally on a 6-minute walk test but then was found sound asleep when I was ready to see him a little while later. I suspected he had undiagnosed sleep apnea, and therefore had an increased risk of postoperative pulmonary complications, but what evidence would I have to delay his surgery to diagnose the sleep apnea and stabilize him on CPAP?

Dr. Smetana: For a patient with clinically suspected but undiagnosed sleep apnea, we have some evidence that the diagnosis should be pursued before surgery is performed.⁸ If the surgery were elective, it would be appropriate to have the patient evaluated and, if obstructive sleep apnea were diagnosed, treated in the customary way with CPAP. For patients who are hospitalized after surgery, CPAP can be continued as soon as possible in the hospital.

I would not have made this recommendation a few years ago, but now the evidence is more compelling. However, at this point I would not recommend routine preoperative screening of all patients for sleep apnea. Ongoing research is looking at this question.

Follow-up question: How long should surgery be delayed to optimize the patient on CPAP?

Dr. Smetana: Risk for postoperative respiratory failure is reduced very quickly after initiating CPAP therapy. A week would probably be sufficient, but there are no good data to specifically address that question.

Question from the audience: What about patients with asthma who are undergoing surgery—which ones benefit from stress-level steroids and preoperative nebulizer therapy?

Dr. Smetana: Surprisingly, asthma—if well controlled—is not a risk factor for postoperative pulmonary complications. Patients within 80% of their predicted or personal best peak flow appear to have a risk similar to that of patients without asthma. For patients with uncontrolled or poorly controlled asthma, the general rule is the same as for patients with COPD: treat them the same as if they weren’t having surgery. If a patient with asthma has a clinical indication for cortico­steroids based on his or her condition, give cortico­steroids whether or not surgery is planned. Corticosteroids are safe and do not raise the risk of postoperative wound complications. But we have no evidence to support routine use of steroids for all patients with asthma simply because elective surgery is planned.

Follow-up question: Do you optimize poorly controlled patients with oral prednisone for several days preoperatively, or do you use a stress protocol?

Dr. Smetana: For a patient whom you would normally treat with an outpatient course of prednisone, you should do just that. For a patient with an exacerbation severe enough to require admission for intravenous steroids and inhaled nebulizer therapy, then you should use that strategy. If the surgery is elective, it should be delayed until the patient is at his or her personal best.

Tolerance of an enteral diet is one of the fundamental components of postoperative wellness, along with the ability to mobilize freely without supplemental oxygen and a readiness to be discharged home as soon as possible. Accordingly, post­operative gastrointestinal (GI) tract dysfunction is best defined as intolerance of an enteral diet after having been tolerant of one preoperatively. I prefer the term postoperative GI tract dysfunction over postoperative ileus, as ileus is ill defined, covering a wide spectrum of clinical signs and having a range of published incidences so broad (5%–100%) that it defies useful discussion.

GI DYSFUNCTION: A COMMON POSTOPERATIVE MORBIDITY

Postoperative GI tract dysfunction is common, as illustrated by a large prospective cohort study at Duke University Medical Center³ that used the Postoperative Morbidity Survey (which has since been validated⁴) to document complications following major noncardiac surgery (ie, anticipated duration > 2 hours and anticipated blood loss > 500 mL). Hospital discharge was delayed in 27% of the study’s 438 patients as a result of a postoperative complication, and GI dysfunction was the most common type of complication overall and on postoperative days 5, 8, and 15. Episodes of GI dysfunction ranged from intolerance of an enteral diet to ischemic gut resulting in multiple organ failure.³

Adapted from a PowerPoint slide developed by Dr. M.P.W. Grocott.

A MULTIFACTORIAL PATHOGENESIS

The pathophysiology of postoperative GI tract dysfunction can be ischemic, metabolic, toxic, neurogenic, myogenic, pharmacologic, or mechanical.

It is important to recognize that in many cases no single factor explains the whole story behind postsurgical GI tract dysfunction, and none of these factors is an ipso facto cause of such dysfunction. For instance, a “mechanical” pathogenesis refers to any manipulation of the gut that causes an inflammatory response in the gut’s various layers, resulting in injury.^5,6 However, GI tract dysfunction commonly occurs after operations (including laparoscopic procedures) in which the gut was not handled at all. Similarly, in terms of a pharmacologic pathophysiology, while opioids can affect GI propulsion and cause constipation,^7,8 avoidance of opioid use does not ensure prevention of GI tract dysfunction. Moreover, opioid abusers do not generally exhibit intolerance of enteral nutrition.

A common mechanism that is often ignored is peri­operative gut ischemia resulting in low-grade injury. Low-grade hypovolemia can cause loss of perfusion to the tip of the microvillus, triggering apoptosis and potentially necrosis, which typically requires about 3 days for recovery. An experiment among 6 healthy volunteers who underwent elective hemorrhage (25% of blood volume removed) over 1 hour demonstrated that gastric tonometry was an earlier indicator of hypovolemia than were commonly measured hemodynamic variables such as invasive blood pressure, stroke volume, heart rate, and lactate and arterial blood gas measurements.⁹

FLUID LOADING AIDS GI RECOVERY

A targeted increase of intravascular volume and global blood flow perioperatively has been shown repeatedly to improve surgical outcome.^10–24 In clinical trials, the most common intervention to achieve the predetermined hemo­dynamic goal has been fluid loading. Overall, targeted increases in perioperative global blood flow have been associated with reduced mortality,²⁵ with the presumed mechanism being maintenance of end-organ perfusion.

The role of end-organ perfusion maintenance was confirmed in a controlled study of 60 patients under­going cardiac surgery in which perioperative fluid loading (with colloid) maintained gut perfusion as measured by gastric tonometry, whereas a control group had a reproducible reduction in gut perfusion.¹⁵ Fluid loading was associated with a significant reduction in the incidence of gut mucosal hypoperfusion—from 56% to 7%—and significant reductions in the incidence of minor and major complications, mean days in the hospital, and mean days in the intensive care unit.

Fluid type matters

The type of intraoperative fluid loading is a factor in postoperative recovery.

Colloid vs crystalloid. Moretti et al found that colloid (6% hetastarch in saline or 6% hetastarch in balanced salt) was superior to crystalloid (lactated Ringer’s solution) in preventing nausea, severe pain, vomiting, periorbital edema, and double vision postoperatively (P < .05 for all) despite comparable hemodynamic profiles.²⁶

Ringer’s vs normal saline. Williams et al compared intravenous lactated Ringer’s solution with normal saline (0.9% sodium chloride) in a randomized study of healthy volunteers.²⁷ The group that received normal saline demonstrated central nervous system changes and a much higher incidence of abdominal discomfort, a finding consistent with the toxic properties of chlorine to the gut.

Balanced electrolyte solutions vs saline-based fluids. Wilkes et al compared crystalloid and colloid solutions with physiologically balanced electrolyte formulations (Hextend) against saline-based fluids (Hespan) in elderly surgical patients.²⁸ They found that balanced electrolyte solutions were superior in improving gastric mucosal perfusion and preventing hyperchloremic metabolic acidosis. As a result of a reduction in GI tract perfusion, postoperative vomiting was more frequent in the group receiving saline-based fluids.

Evidence for Doppler-guided fluid management

Use of esophageal Doppler ultrasonography to guide fluid administration intraoperatively is fairly common in the United Kingdom and is based on randomized controlled trials showing that Doppler-guided colloid administration to maximize stroke volume reduces morbidity and length of hospital stay in surgical patients. In one government-supported study of 128 colorectal resection patients, Doppler-guided small boluses of colloid increased stroke volume, cardiac output, and oxygen delivery compared with conventional (central venous pressure–based) fluid management.²⁹ Gut function improved significantly faster with Doppler-guided fluid management as evidenced by a more rapid return of flatus, opening of bowels, and achievement of a full diet, and by faster discharge from the hospital. The incidence of GI complications was reduced from 45.3% in the conventional management group to 14.1% in the Doppler group. The relative risk of GI tract dysfunction was 5.3 times higher with conventional management.

In addition to fluid loading, a number of other methods have been studied in an attempt to reduce the incidence of postoperative GI tract dysfunction.

Epidural neostigmine: Improvement in some measures

Epidural neostigmine was compared with saline control in a randomized study of 45 patients scheduled for abdominal aortic surgery.³⁰ Time to first bowel sounds and time to first flatus were significantly shorter in the neostigmine group, but time to first defecation and the incidence of post­operative complications were similar between the groups.

Laxatives speed return of GI function

In a study of 53 women undergoing fast-track hysterectomy, recovery of GI tract function was faster in those randomized to receive laxatives (magnesium oxide and disodium phosphate) starting 6 hours postoperatively compared with those receiving placebo.³¹ Median time to first defecation was reduced from 69 hours in the placebo group to 45 hours in the laxative group (P < .0001), and postoperative hospitalization was shortened by a median of 1 day in the laxative group. There were no significant between-group differences in pain scores, postoperative nausea and vomiting, or the use of morphine or antiemetics.

Fentanyl reduces gastric myoelectrical activity

Intravenous administration of the opioid fentanyl significantly reduced gastric myoelectrical activity in an uncontrolled study of 20 patients undergoing elective surgery, but wide variation in effect was observed among patients.³² There was no correlation between the myoelectrical outcome and the presence of polymorphisms of the mu-opioid receptor gene.

Systemic lidocaine accelerates return of bowel function

Perioperative administration of systemic lidocaine, given as a 1.5-mg/kg bolus followed by continuous infusion at 2 mg/min, accelerated the return of bowel function and shortened the length of hospital stay compared with placebo in a randomized study of 60 colorectal surgery patients.³³

Early oral feeding cuts length of stay

A recent meta-analysis of randomized trials found that early oral intake of fluids and food after major abdominal gynecologic surgery was associated with an increased risk of nausea but a reduced length of hospital stay.³⁴ The authors recommended an individualized approach to early feeding, and called for cost-effectiveness and patient satisfaction studies.

Mosapride improves gastric emptying

Mosapride is a 5-HT₄ agonist that has been shown to improve gastric emptying in a randomized controlled study of 40 patients undergoing laparoscopic colectomy.³⁵ Time to first postoperative bowel movement, time to maximal gastric emptying rate, and postoperative hospital stay were all significantly shorter in patients receiving mosapride versus control. Mosapride is not currently approved for marketing in the United States.

Mu-opioid antagonists: Some show promise, others don’t

Mu-opioid receptor antagonists have been developed primarily to reverse opioid-induced bowel dysfunction. Commercially available drugs in this class include alvimopan, methylnaltrexone, nalbuphine, and naloxone. A recent meta-analysis of 23 randomized controlled studies of these agents for opioid-induced bowel dysfunction concluded that alvimopan and methylnaltrexone were superior to placebo but that evidence was insufficient for the safety or efficacy of naloxone and nalbuphine.³⁶

Nasogastric decompression: Usually more harm than benefit

Prophylactic nasogastric decompression is an intervention devoid of evidence. A meta-analysis of 33 studies encompassing 5,240 patients randomized to routine nasogastric tube placement, selective nasogastric tube use, or no nasogastric tube placement after abdominal surgery found no advantage to routine nasogastric tube use.³⁷ In fact, patients not receiving routine tube placement had a significantly earlier return of bowel function and a significant decrease in pulmonary complications. The incidence of anastomotic leak was not different among the groups. Routine tube use was associated with a lower incidence of vomiting but more patient discomfort. The clear conclusion is that, in most situations, elective placement of a nasogastric tube only causes harm.

Chewing gum: A simple intervention that works

In a recent meta-analysis of five randomized controlled trials, the simple intervention of gum chewing after colorectal surgery significantly accelerated the time to flatus and time to defecation, and was associated with a nonsignificant trend toward a shorter postoperative hospital stay.³⁸

CONCLUSIONS ON MANAGEMENT

Traditional measures intended to reduce the incidence of postoperative GI tract dysfunction—administration of prokinetic drugs, placement of nasogastric tubes, avoidance of food and fluids—are not beneficial and are often harmful. Administration of targeted amounts of fluid to optimize ventricular filling and end-organ perfusion has repeatedly been demonstrated to improve outcomes, particularly those related to GI tract perfusion and function. Administration of larger volumes of colloid, to achieve predetermined increases in stroke volume, improves gut perfusion and reduces the incidence of GI tract dysfunction.

Many simple, inexpensive, and readily available strategies for preventing or reversing postoperative GI tract dysfunction have some degree of evidence-based support and should be considered. I would recommend a multimodal approach that includes a limited surgical incision, regional local anesthesia without use of opioids, immediate postoperative mobilization, early enteral feeding, and postoperative gum chewing.¹ Such an approach promises to reduce GI tract dysfunction and other postoperative complications as well as to shorten hospital stay.

Question from the audience: You mentioned the selective use of nasogastric tubes. In which patients would you use them?

Dr. Mythen: For upper GI surgeries—esophagectomy, for example—a nasogastric tube is inevitable. Beyond that, the specific indications for tube placement are very limited. At our institution, we no longer place nasogastric tubes following the vast majority of GI tract operations, with esophagectomy being the exception.

Question from the audience: Would you comment on the selective contribution of thoracic epidural analgesia with respect to early feeding after abdominal or colon surgery?

Dr. Mythen: If you’re an enthusiast for thoracic epidurals, you can present the literature in a way that definitively demonstrates a huge advantage to thoracic epidurals. When they work well for the individual, they are fantastic, but you must have a very effective team and system to deliver success to the whole patient population. At our institution the failure rate 20 to 24 hours postoperatively is about 50%.

Question from the audience: I’m an internist and I’ve never heard of the esophageal Doppler-directed fluid bolus protocol—or of anyone using colloids at all. Is that something that is generally practiced in the United States?

Dr. Mythen: Some institutions are practicing goal-directed fluid management now. If you measure stroke volume and give small boluses of colloid, you need a lot less fluid to achieve a higher intravascular volume and goal. At our institution, we’ve repackaged it as “goal-directed fluid restriction” to gain acceptance among surgeons. Uptake has been slower in the United States, though studies here have reinforced the message and been supported by editorials. Guessing about fluids, which we’ve done historically, is not very smart. One thing that differentiates an anesthesiologist from an anesthetic technician is the ability to give goal-directed fluid therapy. The ability to act in a targeted fashion makes it possible to achieve an appropriate physiological goal, but it is more difficult.

Question from the audience: In terms of maintenance fluids and chloride toxicity, is there an alternative to D5 half-normal saline for maintenance fluid?

Dr. Mythen: We don’t have a very good postoperative maintenance fluid; D5 half-normal with some potassium is probably as good as it gets at present. I emphasize getting patients to drink as quickly as possible. If they’re not drinking (not using the GI tract), they need a very high level of physician input because fluid balance is rocket science. The GI tract is very clever. Once patients are drinking and eating, they’re fine, but if they still have an intravenous line in, close attention is required.

Question from the audience: Would you use lactated Ringer’s solution in a patient who is just not eating or drinking?

Dr. Mythen: I do, actually. I tend to mix it in with some D5 half-normal saline because lactated Ringer’s is a great solution. The body can use the lactate to make sugar if necessary. The brain is one of the few organs that will metabolize lactate.

Follow-up question: Would you use it at a lower rate to prevent volume overload?

Dr. Mythen: Yes, at 60 mL/hr. The important thing is that if intravenous fluids are still required, the patient needs to be in a fairly supervised, high-dependency environment. You must address the real issue: Why aren’t they drinking? If the patient is not drinking postoperatively, someone’s done a bad job or there is something that needs fixing.

Question from audience: In the operating room, do you have a preference between albumin and a high-molecular-weight hetastarch like Hextend?

Dr. Mythen: Europe is slightly different in its choice of colloids. We’ve pretty much abandoned the high-molecular-weight starches. We do not use albumin at our institution for cost reasons, and we can’t find any evidence to support its use. We would have to close one intensive care unit bed to be able to afford using albumin. We use low-molecular-weight hydroxyethyl starches, which I believe are now coming into the United States. They have no major coagulation effect.

Tolerance of an enteral diet is one of the fundamental components of postoperative wellness, along with the ability to mobilize freely without supplemental oxygen and a readiness to be discharged home as soon as possible. Accordingly, post­operative gastrointestinal (GI) tract dysfunction is best defined as intolerance of an enteral diet after having been tolerant of one preoperatively. I prefer the term postoperative GI tract dysfunction over postoperative ileus, as ileus is ill defined, covering a wide spectrum of clinical signs and having a range of published incidences so broad (5%–100%) that it defies useful discussion.

GI DYSFUNCTION: A COMMON POSTOPERATIVE MORBIDITY

Postoperative GI tract dysfunction is common, as illustrated by a large prospective cohort study at Duke University Medical Center³ that used the Postoperative Morbidity Survey (which has since been validated⁴) to document complications following major noncardiac surgery (ie, anticipated duration > 2 hours and anticipated blood loss > 500 mL). Hospital discharge was delayed in 27% of the study’s 438 patients as a result of a postoperative complication, and GI dysfunction was the most common type of complication overall and on postoperative days 5, 8, and 15. Episodes of GI dysfunction ranged from intolerance of an enteral diet to ischemic gut resulting in multiple organ failure.³

Adapted from a PowerPoint slide developed by Dr. M.P.W. Grocott.

A MULTIFACTORIAL PATHOGENESIS

The pathophysiology of postoperative GI tract dysfunction can be ischemic, metabolic, toxic, neurogenic, myogenic, pharmacologic, or mechanical.

It is important to recognize that in many cases no single factor explains the whole story behind postsurgical GI tract dysfunction, and none of these factors is an ipso facto cause of such dysfunction. For instance, a “mechanical” pathogenesis refers to any manipulation of the gut that causes an inflammatory response in the gut’s various layers, resulting in injury.^5,6 However, GI tract dysfunction commonly occurs after operations (including laparoscopic procedures) in which the gut was not handled at all. Similarly, in terms of a pharmacologic pathophysiology, while opioids can affect GI propulsion and cause constipation,^7,8 avoidance of opioid use does not ensure prevention of GI tract dysfunction. Moreover, opioid abusers do not generally exhibit intolerance of enteral nutrition.

A common mechanism that is often ignored is peri­operative gut ischemia resulting in low-grade injury. Low-grade hypovolemia can cause loss of perfusion to the tip of the microvillus, triggering apoptosis and potentially necrosis, which typically requires about 3 days for recovery. An experiment among 6 healthy volunteers who underwent elective hemorrhage (25% of blood volume removed) over 1 hour demonstrated that gastric tonometry was an earlier indicator of hypovolemia than were commonly measured hemodynamic variables such as invasive blood pressure, stroke volume, heart rate, and lactate and arterial blood gas measurements.⁹

FLUID LOADING AIDS GI RECOVERY

A targeted increase of intravascular volume and global blood flow perioperatively has been shown repeatedly to improve surgical outcome.^10–24 In clinical trials, the most common intervention to achieve the predetermined hemo­dynamic goal has been fluid loading. Overall, targeted increases in perioperative global blood flow have been associated with reduced mortality,²⁵ with the presumed mechanism being maintenance of end-organ perfusion.

The role of end-organ perfusion maintenance was confirmed in a controlled study of 60 patients under­going cardiac surgery in which perioperative fluid loading (with colloid) maintained gut perfusion as measured by gastric tonometry, whereas a control group had a reproducible reduction in gut perfusion.¹⁵ Fluid loading was associated with a significant reduction in the incidence of gut mucosal hypoperfusion—from 56% to 7%—and significant reductions in the incidence of minor and major complications, mean days in the hospital, and mean days in the intensive care unit.

Fluid type matters

The type of intraoperative fluid loading is a factor in postoperative recovery.

Colloid vs crystalloid. Moretti et al found that colloid (6% hetastarch in saline or 6% hetastarch in balanced salt) was superior to crystalloid (lactated Ringer’s solution) in preventing nausea, severe pain, vomiting, periorbital edema, and double vision postoperatively (P < .05 for all) despite comparable hemodynamic profiles.²⁶

Ringer’s vs normal saline. Williams et al compared intravenous lactated Ringer’s solution with normal saline (0.9% sodium chloride) in a randomized study of healthy volunteers.²⁷ The group that received normal saline demonstrated central nervous system changes and a much higher incidence of abdominal discomfort, a finding consistent with the toxic properties of chlorine to the gut.

Balanced electrolyte solutions vs saline-based fluids. Wilkes et al compared crystalloid and colloid solutions with physiologically balanced electrolyte formulations (Hextend) against saline-based fluids (Hespan) in elderly surgical patients.²⁸ They found that balanced electrolyte solutions were superior in improving gastric mucosal perfusion and preventing hyperchloremic metabolic acidosis. As a result of a reduction in GI tract perfusion, postoperative vomiting was more frequent in the group receiving saline-based fluids.

Evidence for Doppler-guided fluid management

Use of esophageal Doppler ultrasonography to guide fluid administration intraoperatively is fairly common in the United Kingdom and is based on randomized controlled trials showing that Doppler-guided colloid administration to maximize stroke volume reduces morbidity and length of hospital stay in surgical patients. In one government-supported study of 128 colorectal resection patients, Doppler-guided small boluses of colloid increased stroke volume, cardiac output, and oxygen delivery compared with conventional (central venous pressure–based) fluid management.²⁹ Gut function improved significantly faster with Doppler-guided fluid management as evidenced by a more rapid return of flatus, opening of bowels, and achievement of a full diet, and by faster discharge from the hospital. The incidence of GI complications was reduced from 45.3% in the conventional management group to 14.1% in the Doppler group. The relative risk of GI tract dysfunction was 5.3 times higher with conventional management.

In addition to fluid loading, a number of other methods have been studied in an attempt to reduce the incidence of postoperative GI tract dysfunction.

Epidural neostigmine: Improvement in some measures

Epidural neostigmine was compared with saline control in a randomized study of 45 patients scheduled for abdominal aortic surgery.³⁰ Time to first bowel sounds and time to first flatus were significantly shorter in the neostigmine group, but time to first defecation and the incidence of post­operative complications were similar between the groups.

Laxatives speed return of GI function

In a study of 53 women undergoing fast-track hysterectomy, recovery of GI tract function was faster in those randomized to receive laxatives (magnesium oxide and disodium phosphate) starting 6 hours postoperatively compared with those receiving placebo.³¹ Median time to first defecation was reduced from 69 hours in the placebo group to 45 hours in the laxative group (P < .0001), and postoperative hospitalization was shortened by a median of 1 day in the laxative group. There were no significant between-group differences in pain scores, postoperative nausea and vomiting, or the use of morphine or antiemetics.

Fentanyl reduces gastric myoelectrical activity

Intravenous administration of the opioid fentanyl significantly reduced gastric myoelectrical activity in an uncontrolled study of 20 patients undergoing elective surgery, but wide variation in effect was observed among patients.³² There was no correlation between the myoelectrical outcome and the presence of polymorphisms of the mu-opioid receptor gene.

Systemic lidocaine accelerates return of bowel function

Perioperative administration of systemic lidocaine, given as a 1.5-mg/kg bolus followed by continuous infusion at 2 mg/min, accelerated the return of bowel function and shortened the length of hospital stay compared with placebo in a randomized study of 60 colorectal surgery patients.³³

Early oral feeding cuts length of stay

A recent meta-analysis of randomized trials found that early oral intake of fluids and food after major abdominal gynecologic surgery was associated with an increased risk of nausea but a reduced length of hospital stay.³⁴ The authors recommended an individualized approach to early feeding, and called for cost-effectiveness and patient satisfaction studies.

Mosapride improves gastric emptying

Mosapride is a 5-HT₄ agonist that has been shown to improve gastric emptying in a randomized controlled study of 40 patients undergoing laparoscopic colectomy.³⁵ Time to first postoperative bowel movement, time to maximal gastric emptying rate, and postoperative hospital stay were all significantly shorter in patients receiving mosapride versus control. Mosapride is not currently approved for marketing in the United States.

Mu-opioid antagonists: Some show promise, others don’t

Mu-opioid receptor antagonists have been developed primarily to reverse opioid-induced bowel dysfunction. Commercially available drugs in this class include alvimopan, methylnaltrexone, nalbuphine, and naloxone. A recent meta-analysis of 23 randomized controlled studies of these agents for opioid-induced bowel dysfunction concluded that alvimopan and methylnaltrexone were superior to placebo but that evidence was insufficient for the safety or efficacy of naloxone and nalbuphine.³⁶

Nasogastric decompression: Usually more harm than benefit

Prophylactic nasogastric decompression is an intervention devoid of evidence. A meta-analysis of 33 studies encompassing 5,240 patients randomized to routine nasogastric tube placement, selective nasogastric tube use, or no nasogastric tube placement after abdominal surgery found no advantage to routine nasogastric tube use.³⁷ In fact, patients not receiving routine tube placement had a significantly earlier return of bowel function and a significant decrease in pulmonary complications. The incidence of anastomotic leak was not different among the groups. Routine tube use was associated with a lower incidence of vomiting but more patient discomfort. The clear conclusion is that, in most situations, elective placement of a nasogastric tube only causes harm.

Chewing gum: A simple intervention that works

In a recent meta-analysis of five randomized controlled trials, the simple intervention of gum chewing after colorectal surgery significantly accelerated the time to flatus and time to defecation, and was associated with a nonsignificant trend toward a shorter postoperative hospital stay.³⁸

CONCLUSIONS ON MANAGEMENT

Traditional measures intended to reduce the incidence of postoperative GI tract dysfunction—administration of prokinetic drugs, placement of nasogastric tubes, avoidance of food and fluids—are not beneficial and are often harmful. Administration of targeted amounts of fluid to optimize ventricular filling and end-organ perfusion has repeatedly been demonstrated to improve outcomes, particularly those related to GI tract perfusion and function. Administration of larger volumes of colloid, to achieve predetermined increases in stroke volume, improves gut perfusion and reduces the incidence of GI tract dysfunction.

Many simple, inexpensive, and readily available strategies for preventing or reversing postoperative GI tract dysfunction have some degree of evidence-based support and should be considered. I would recommend a multimodal approach that includes a limited surgical incision, regional local anesthesia without use of opioids, immediate postoperative mobilization, early enteral feeding, and postoperative gum chewing.¹ Such an approach promises to reduce GI tract dysfunction and other postoperative complications as well as to shorten hospital stay.

Question from the audience: You mentioned the selective use of nasogastric tubes. In which patients would you use them?

Dr. Mythen: For upper GI surgeries—esophagectomy, for example—a nasogastric tube is inevitable. Beyond that, the specific indications for tube placement are very limited. At our institution, we no longer place nasogastric tubes following the vast majority of GI tract operations, with esophagectomy being the exception.

Question from the audience: Would you comment on the selective contribution of thoracic epidural analgesia with respect to early feeding after abdominal or colon surgery?

Dr. Mythen: If you’re an enthusiast for thoracic epidurals, you can present the literature in a way that definitively demonstrates a huge advantage to thoracic epidurals. When they work well for the individual, they are fantastic, but you must have a very effective team and system to deliver success to the whole patient population. At our institution the failure rate 20 to 24 hours postoperatively is about 50%.

Question from the audience: I’m an internist and I’ve never heard of the esophageal Doppler-directed fluid bolus protocol—or of anyone using colloids at all. Is that something that is generally practiced in the United States?

Dr. Mythen: Some institutions are practicing goal-directed fluid management now. If you measure stroke volume and give small boluses of colloid, you need a lot less fluid to achieve a higher intravascular volume and goal. At our institution, we’ve repackaged it as “goal-directed fluid restriction” to gain acceptance among surgeons. Uptake has been slower in the United States, though studies here have reinforced the message and been supported by editorials. Guessing about fluids, which we’ve done historically, is not very smart. One thing that differentiates an anesthesiologist from an anesthetic technician is the ability to give goal-directed fluid therapy. The ability to act in a targeted fashion makes it possible to achieve an appropriate physiological goal, but it is more difficult.

Question from the audience: In terms of maintenance fluids and chloride toxicity, is there an alternative to D5 half-normal saline for maintenance fluid?

Dr. Mythen: We don’t have a very good postoperative maintenance fluid; D5 half-normal with some potassium is probably as good as it gets at present. I emphasize getting patients to drink as quickly as possible. If they’re not drinking (not using the GI tract), they need a very high level of physician input because fluid balance is rocket science. The GI tract is very clever. Once patients are drinking and eating, they’re fine, but if they still have an intravenous line in, close attention is required.

Question from the audience: Would you use lactated Ringer’s solution in a patient who is just not eating or drinking?

Dr. Mythen: I do, actually. I tend to mix it in with some D5 half-normal saline because lactated Ringer’s is a great solution. The body can use the lactate to make sugar if necessary. The brain is one of the few organs that will metabolize lactate.

Follow-up question: Would you use it at a lower rate to prevent volume overload?

Dr. Mythen: Yes, at 60 mL/hr. The important thing is that if intravenous fluids are still required, the patient needs to be in a fairly supervised, high-dependency environment. You must address the real issue: Why aren’t they drinking? If the patient is not drinking postoperatively, someone’s done a bad job or there is something that needs fixing.

Question from audience: In the operating room, do you have a preference between albumin and a high-molecular-weight hetastarch like Hextend?

Dr. Mythen: Europe is slightly different in its choice of colloids. We’ve pretty much abandoned the high-molecular-weight starches. We do not use albumin at our institution for cost reasons, and we can’t find any evidence to support its use. We would have to close one intensive care unit bed to be able to afford using albumin. We use low-molecular-weight hydroxyethyl starches, which I believe are now coming into the United States. They have no major coagulation effect.

Tolerance of an enteral diet is one of the fundamental components of postoperative wellness, along with the ability to mobilize freely without supplemental oxygen and a readiness to be discharged home as soon as possible. Accordingly, post­operative gastrointestinal (GI) tract dysfunction is best defined as intolerance of an enteral diet after having been tolerant of one preoperatively. I prefer the term postoperative GI tract dysfunction over postoperative ileus, as ileus is ill defined, covering a wide spectrum of clinical signs and having a range of published incidences so broad (5%–100%) that it defies useful discussion.

GI DYSFUNCTION: A COMMON POSTOPERATIVE MORBIDITY

Postoperative GI tract dysfunction is common, as illustrated by a large prospective cohort study at Duke University Medical Center³ that used the Postoperative Morbidity Survey (which has since been validated⁴) to document complications following major noncardiac surgery (ie, anticipated duration > 2 hours and anticipated blood loss > 500 mL). Hospital discharge was delayed in 27% of the study’s 438 patients as a result of a postoperative complication, and GI dysfunction was the most common type of complication overall and on postoperative days 5, 8, and 15. Episodes of GI dysfunction ranged from intolerance of an enteral diet to ischemic gut resulting in multiple organ failure.³

Adapted from a PowerPoint slide developed by Dr. M.P.W. Grocott.

A MULTIFACTORIAL PATHOGENESIS

The pathophysiology of postoperative GI tract dysfunction can be ischemic, metabolic, toxic, neurogenic, myogenic, pharmacologic, or mechanical.

It is important to recognize that in many cases no single factor explains the whole story behind postsurgical GI tract dysfunction, and none of these factors is an ipso facto cause of such dysfunction. For instance, a “mechanical” pathogenesis refers to any manipulation of the gut that causes an inflammatory response in the gut’s various layers, resulting in injury.^5,6 However, GI tract dysfunction commonly occurs after operations (including laparoscopic procedures) in which the gut was not handled at all. Similarly, in terms of a pharmacologic pathophysiology, while opioids can affect GI propulsion and cause constipation,^7,8 avoidance of opioid use does not ensure prevention of GI tract dysfunction. Moreover, opioid abusers do not generally exhibit intolerance of enteral nutrition.

A common mechanism that is often ignored is peri­operative gut ischemia resulting in low-grade injury. Low-grade hypovolemia can cause loss of perfusion to the tip of the microvillus, triggering apoptosis and potentially necrosis, which typically requires about 3 days for recovery. An experiment among 6 healthy volunteers who underwent elective hemorrhage (25% of blood volume removed) over 1 hour demonstrated that gastric tonometry was an earlier indicator of hypovolemia than were commonly measured hemodynamic variables such as invasive blood pressure, stroke volume, heart rate, and lactate and arterial blood gas measurements.⁹

FLUID LOADING AIDS GI RECOVERY

A targeted increase of intravascular volume and global blood flow perioperatively has been shown repeatedly to improve surgical outcome.^10–24 In clinical trials, the most common intervention to achieve the predetermined hemo­dynamic goal has been fluid loading. Overall, targeted increases in perioperative global blood flow have been associated with reduced mortality,²⁵ with the presumed mechanism being maintenance of end-organ perfusion.

The role of end-organ perfusion maintenance was confirmed in a controlled study of 60 patients under­going cardiac surgery in which perioperative fluid loading (with colloid) maintained gut perfusion as measured by gastric tonometry, whereas a control group had a reproducible reduction in gut perfusion.¹⁵ Fluid loading was associated with a significant reduction in the incidence of gut mucosal hypoperfusion—from 56% to 7%—and significant reductions in the incidence of minor and major complications, mean days in the hospital, and mean days in the intensive care unit.

Fluid type matters

The type of intraoperative fluid loading is a factor in postoperative recovery.

Colloid vs crystalloid. Moretti et al found that colloid (6% hetastarch in saline or 6% hetastarch in balanced salt) was superior to crystalloid (lactated Ringer’s solution) in preventing nausea, severe pain, vomiting, periorbital edema, and double vision postoperatively (P < .05 for all) despite comparable hemodynamic profiles.²⁶

Ringer’s vs normal saline. Williams et al compared intravenous lactated Ringer’s solution with normal saline (0.9% sodium chloride) in a randomized study of healthy volunteers.²⁷ The group that received normal saline demonstrated central nervous system changes and a much higher incidence of abdominal discomfort, a finding consistent with the toxic properties of chlorine to the gut.

Balanced electrolyte solutions vs saline-based fluids. Wilkes et al compared crystalloid and colloid solutions with physiologically balanced electrolyte formulations (Hextend) against saline-based fluids (Hespan) in elderly surgical patients.²⁸ They found that balanced electrolyte solutions were superior in improving gastric mucosal perfusion and preventing hyperchloremic metabolic acidosis. As a result of a reduction in GI tract perfusion, postoperative vomiting was more frequent in the group receiving saline-based fluids.

Evidence for Doppler-guided fluid management

Use of esophageal Doppler ultrasonography to guide fluid administration intraoperatively is fairly common in the United Kingdom and is based on randomized controlled trials showing that Doppler-guided colloid administration to maximize stroke volume reduces morbidity and length of hospital stay in surgical patients. In one government-supported study of 128 colorectal resection patients, Doppler-guided small boluses of colloid increased stroke volume, cardiac output, and oxygen delivery compared with conventional (central venous pressure–based) fluid management.²⁹ Gut function improved significantly faster with Doppler-guided fluid management as evidenced by a more rapid return of flatus, opening of bowels, and achievement of a full diet, and by faster discharge from the hospital. The incidence of GI complications was reduced from 45.3% in the conventional management group to 14.1% in the Doppler group. The relative risk of GI tract dysfunction was 5.3 times higher with conventional management.

In addition to fluid loading, a number of other methods have been studied in an attempt to reduce the incidence of postoperative GI tract dysfunction.

Epidural neostigmine: Improvement in some measures

Epidural neostigmine was compared with saline control in a randomized study of 45 patients scheduled for abdominal aortic surgery.³⁰ Time to first bowel sounds and time to first flatus were significantly shorter in the neostigmine group, but time to first defecation and the incidence of post­operative complications were similar between the groups.

Laxatives speed return of GI function

In a study of 53 women undergoing fast-track hysterectomy, recovery of GI tract function was faster in those randomized to receive laxatives (magnesium oxide and disodium phosphate) starting 6 hours postoperatively compared with those receiving placebo.³¹ Median time to first defecation was reduced from 69 hours in the placebo group to 45 hours in the laxative group (P < .0001), and postoperative hospitalization was shortened by a median of 1 day in the laxative group. There were no significant between-group differences in pain scores, postoperative nausea and vomiting, or the use of morphine or antiemetics.

Fentanyl reduces gastric myoelectrical activity

Intravenous administration of the opioid fentanyl significantly reduced gastric myoelectrical activity in an uncontrolled study of 20 patients undergoing elective surgery, but wide variation in effect was observed among patients.³² There was no correlation between the myoelectrical outcome and the presence of polymorphisms of the mu-opioid receptor gene.

Systemic lidocaine accelerates return of bowel function

Perioperative administration of systemic lidocaine, given as a 1.5-mg/kg bolus followed by continuous infusion at 2 mg/min, accelerated the return of bowel function and shortened the length of hospital stay compared with placebo in a randomized study of 60 colorectal surgery patients.³³

Early oral feeding cuts length of stay

A recent meta-analysis of randomized trials found that early oral intake of fluids and food after major abdominal gynecologic surgery was associated with an increased risk of nausea but a reduced length of hospital stay.³⁴ The authors recommended an individualized approach to early feeding, and called for cost-effectiveness and patient satisfaction studies.

Mosapride improves gastric emptying

Mosapride is a 5-HT₄ agonist that has been shown to improve gastric emptying in a randomized controlled study of 40 patients undergoing laparoscopic colectomy.³⁵ Time to first postoperative bowel movement, time to maximal gastric emptying rate, and postoperative hospital stay were all significantly shorter in patients receiving mosapride versus control. Mosapride is not currently approved for marketing in the United States.

Mu-opioid antagonists: Some show promise, others don’t

Mu-opioid receptor antagonists have been developed primarily to reverse opioid-induced bowel dysfunction. Commercially available drugs in this class include alvimopan, methylnaltrexone, nalbuphine, and naloxone. A recent meta-analysis of 23 randomized controlled studies of these agents for opioid-induced bowel dysfunction concluded that alvimopan and methylnaltrexone were superior to placebo but that evidence was insufficient for the safety or efficacy of naloxone and nalbuphine.³⁶

Nasogastric decompression: Usually more harm than benefit

Prophylactic nasogastric decompression is an intervention devoid of evidence. A meta-analysis of 33 studies encompassing 5,240 patients randomized to routine nasogastric tube placement, selective nasogastric tube use, or no nasogastric tube placement after abdominal surgery found no advantage to routine nasogastric tube use.³⁷ In fact, patients not receiving routine tube placement had a significantly earlier return of bowel function and a significant decrease in pulmonary complications. The incidence of anastomotic leak was not different among the groups. Routine tube use was associated with a lower incidence of vomiting but more patient discomfort. The clear conclusion is that, in most situations, elective placement of a nasogastric tube only causes harm.

Chewing gum: A simple intervention that works

In a recent meta-analysis of five randomized controlled trials, the simple intervention of gum chewing after colorectal surgery significantly accelerated the time to flatus and time to defecation, and was associated with a nonsignificant trend toward a shorter postoperative hospital stay.³⁸

CONCLUSIONS ON MANAGEMENT

Traditional measures intended to reduce the incidence of postoperative GI tract dysfunction—administration of prokinetic drugs, placement of nasogastric tubes, avoidance of food and fluids—are not beneficial and are often harmful. Administration of targeted amounts of fluid to optimize ventricular filling and end-organ perfusion has repeatedly been demonstrated to improve outcomes, particularly those related to GI tract perfusion and function. Administration of larger volumes of colloid, to achieve predetermined increases in stroke volume, improves gut perfusion and reduces the incidence of GI tract dysfunction.

Many simple, inexpensive, and readily available strategies for preventing or reversing postoperative GI tract dysfunction have some degree of evidence-based support and should be considered. I would recommend a multimodal approach that includes a limited surgical incision, regional local anesthesia without use of opioids, immediate postoperative mobilization, early enteral feeding, and postoperative gum chewing.¹ Such an approach promises to reduce GI tract dysfunction and other postoperative complications as well as to shorten hospital stay.

Question from the audience: You mentioned the selective use of nasogastric tubes. In which patients would you use them?

Dr. Mythen: For upper GI surgeries—esophagectomy, for example—a nasogastric tube is inevitable. Beyond that, the specific indications for tube placement are very limited. At our institution, we no longer place nasogastric tubes following the vast majority of GI tract operations, with esophagectomy being the exception.

Question from the audience: Would you comment on the selective contribution of thoracic epidural analgesia with respect to early feeding after abdominal or colon surgery?

Dr. Mythen: If you’re an enthusiast for thoracic epidurals, you can present the literature in a way that definitively demonstrates a huge advantage to thoracic epidurals. When they work well for the individual, they are fantastic, but you must have a very effective team and system to deliver success to the whole patient population. At our institution the failure rate 20 to 24 hours postoperatively is about 50%.

Question from the audience: I’m an internist and I’ve never heard of the esophageal Doppler-directed fluid bolus protocol—or of anyone using colloids at all. Is that something that is generally practiced in the United States?

Dr. Mythen: Some institutions are practicing goal-directed fluid management now. If you measure stroke volume and give small boluses of colloid, you need a lot less fluid to achieve a higher intravascular volume and goal. At our institution, we’ve repackaged it as “goal-directed fluid restriction” to gain acceptance among surgeons. Uptake has been slower in the United States, though studies here have reinforced the message and been supported by editorials. Guessing about fluids, which we’ve done historically, is not very smart. One thing that differentiates an anesthesiologist from an anesthetic technician is the ability to give goal-directed fluid therapy. The ability to act in a targeted fashion makes it possible to achieve an appropriate physiological goal, but it is more difficult.

Question from the audience: In terms of maintenance fluids and chloride toxicity, is there an alternative to D5 half-normal saline for maintenance fluid?

Dr. Mythen: We don’t have a very good postoperative maintenance fluid; D5 half-normal with some potassium is probably as good as it gets at present. I emphasize getting patients to drink as quickly as possible. If they’re not drinking (not using the GI tract), they need a very high level of physician input because fluid balance is rocket science. The GI tract is very clever. Once patients are drinking and eating, they’re fine, but if they still have an intravenous line in, close attention is required.

Question from the audience: Would you use lactated Ringer’s solution in a patient who is just not eating or drinking?

Dr. Mythen: I do, actually. I tend to mix it in with some D5 half-normal saline because lactated Ringer’s is a great solution. The body can use the lactate to make sugar if necessary. The brain is one of the few organs that will metabolize lactate.

Follow-up question: Would you use it at a lower rate to prevent volume overload?

Dr. Mythen: Yes, at 60 mL/hr. The important thing is that if intravenous fluids are still required, the patient needs to be in a fairly supervised, high-dependency environment. You must address the real issue: Why aren’t they drinking? If the patient is not drinking postoperatively, someone’s done a bad job or there is something that needs fixing.

Question from audience: In the operating room, do you have a preference between albumin and a high-molecular-weight hetastarch like Hextend?

Dr. Mythen: Europe is slightly different in its choice of colloids. We’ve pretty much abandoned the high-molecular-weight starches. We do not use albumin at our institution for cost reasons, and we can’t find any evidence to support its use. We would have to close one intensive care unit bed to be able to afford using albumin. We use low-molecular-weight hydroxyethyl starches, which I believe are now coming into the United States. They have no major coagulation effect.

CASE 1: RADICAL PROSTATECTOMY IN A MAN WITH ACUTE DEEP VEIN THROMBOSIS

A 69-year-old man is seen in the preoperative clinic 1 week before a scheduled radical prostatectomy. He has been diagnosed with femoral deep vein thrombosis (DVT) following a complaint of calf soreness.

Question 1.1: How would you treat him for his DVT?

A. Intravenous (IV) unfractionated heparin (UFH)

B. Low-molecular-weight heparin (LMWH)

C. Inferior vena cava (IVC) filter

D. Combination of pharmacologic therapy and then an IVC filter

Dr. Steven L. Cohn: The latest edition of the American College of Chest Physicians (ACCP) evidence-based guidelines on antithrombotic therapy recommends the use of therapeutic-dose subcutaneous LMWH over IV UFH for initial treatment of acute DVT in the outpatient or inpatient setting.¹ Additionally, indications for an IVC filter include the prevention of pulmonary embolism (PE) in a patient with DVT who requires full-dose anticoagulation but cannot receive it, as would be the case here if the patient proceeds with surgery as scheduled. So if surgery will be postponed, the best option is LMWH; if surgery will not be postponed, the best answer is a combination of pharmacologic therapy with low-dose LMWH and an IVC filter, preferably a retrievable one.²

Question 1.2: You recommend postponing surgery, but the patient is worried about metastatic disease. For how long should surgery be postponed?

A. 2 weeks

B. 1 month

C. 2 months

D. 3 months

E. 6 months

Dr. Cohn: In the absence of anticoagulation therapy, the risk of venous thromboembolism (VTE) is approximately 40% (~1% per day) during the first month following an acute VTE and then declines markedly, to approximately 10%, during the second and third months following the acute event.³ Therefore, I would suggest that the patient wait at least 1 month after an acute DVT before undergoing surgery.

Dr. BobbieJean Sweitzer: This patient is in a hypercoagulable state, and the surgery itself will induce excess hypercoagulability. With a femoral DVT already present, his risk of VTE or PE is likely to be greater than 1% per day during the first month. If he does develop a PE, it may potentially be fatal.

Question 1.3: According to the patient, the surgeon and the internist discussed options, but the surgeon “doesn’t believe in filters” and the patient doesn’t want to postpone the procedure, despite your recommendation. Two weeks later he shows up for surgery having stopped his LMWH 3 days before. What would you do?

A. Cancel the surgery and restart full-dose LMWH

B. Proceed with prophylactic-dose LMWH

C. Proceed after giving a full therapeutic dose

D. Insert a filter and give DVT prophylaxis

Dr. Cohn: A bridging protocol should have been discussed with the surgeon and anesthesiologist before the procedure. Therapeutic levels of LMWH persist as long as 18 hours after discontinuation; therefore, the ACCP recommends interrupting LMWH 24 hours before surgery.⁴

Dr. Sweitzer: The lack of a bridging protocol in this case created a problem. The patient was afraid to continue anticoagulation after hearing the internist and surgeon disagree about the plan, and thus stopped it entirely, and he did not want to delay surgery because he was fearful of metastasis. The surgeon was adamant that IVC filters don’t work. The internist was concerned that the patient was at high risk for a PE. Even though the documented risk of postponing radical prostatectomy for a short time is inconsequential, I was convinced that the patient would not believe this if metastasis were to develop in the future.

Question 1.4: How would you have managed his anticoagulation perioperatively?

A. Stop LMWH 12 hours before surgery and restart at full dose 12 to 24 hours after surgery

B. Stop LMWH 24 hours before surgery and restart at full dose 24 hours after surgery

C. Stop LMWH 24 hours before surgery and restart prophylactic dosing 12 to 24 hours after surgery, and then full-dose LMWH in 48 to 72 hours

D. Stop LMWH 24 hours before surgery and restart at full dose 72 hours after surgery

Dr. Cohn: The correct timing for stopping LMWH is 24 hours before surgery. As for how to resume anticoagulation in patients at high risk for VTE or those undergoing major surgery, the latest ACCP guidelines recommend the following⁴:

• Reinitiation of anticoagulation 12 to 24 hours postoperatively, assuming adequate hemostasis in patients not at high risk for bleeding
• Use of a prophylactic dose or no anticoagulation for up to 72 hours if the patient is at high risk for bleeding.

These recommendations are a departure from previous practice, in which we routinely restarted anticoagulation 6 to 12 hours postoperatively.

Dr. Sweitzer: According to guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA),⁵ if twice-daily LMWH is stopped 24 hours ahead of time (as long as patients have normal renal function), it is safe to perform epidural or spinal anesthesia, if either is an option. If full-dose UFH is used, the partial thrombo­plastin time (PTT) is monitored and central neuraxial blockade may be done if the PTT is in the normal range, which typically is 2 to 6 hours after UFH is stopped.

Additionally, the platelet count should be checked every 3 days postoperatively while the patient is on UFH or LMWH. It may be just as important to monitor the platelet count preoperatively if the patient has been on UFH or LMWH for an extended duration, especially if a central neuraxial anesthetic technique is planned.

Dr. Cohn: The reason for monitoring the platelet count is the potential for heparin-induced thrombocytopenia in patients on UFH. I recently encountered a patient who developed postoperative heparin-induced thrombo­cytopenia with thrombosis while on LMWH, which is relatively uncommon compared with UFH.

Case resolution

After much discussion of the risk of a significant PE with the patient, family, urologist, and vascular surgeon, it is decided that a temporary IVC filter will be placed in the operating room immediately after induction of general anesthesia and before the prostatectomy. The operation is delayed about 1 hour to allow this option. The patient is successfully treated and has the IVC filter removed 1 month postoperatively.

A 78-year-old obese Russian-speaking man is seen in the preoperative clinic prior to a scheduled radical cystectomy for highly invasive bladder cancer. He is a poor historian and argues with the several family members accompanying him, but it is determined that his medical history includes hypertension, diabetes mellitus, a myocardial infarction (MI) 5 years previously (in Russia), and stable angina that is determined to be class II.

He had no previous work-up and no electrocardiogram (ECG). His medications are aspirin, metoprolol, and metformin. His blood pressure is 190/100 mm Hg, heart rate 90 beats per minute, and body mass index 32. On examination, there is no murmur, S3 gallop, or rales. His blood glucose is 220 mg/dL, and his creatinine is slightly elevated (1.4 mg/dL). ECG verifies a prior MI.

Question 2.1: Which of the following additional tests should be ordered preoperatively?

A. Hemoglobin (Hb) A_1c

B. Lipid profile

C. Both

D. Neither

Dr. Sweitzer: Because the surgery is not elective, no immediate benefit would be achieved by ordering either an HbA_1c or a lipid profile. However, if you view the preoperative evaluation as an opportunity to manage risk factors over the long term, then it may be a good idea to order the lipid profile because this patient has rarely engaged the health care system. Likewise, the HbA_1c can be ordered to set in place his long-term management. Sometimes we focus on the preoperative visit only in the context of the surgery, but if a test or intervention is appropriate and needed for long-term management, then it is appropriate to do now.

Dr. Cohn: There is no evidence to support using the preoperative HbA_1c to alter management decisions. I would not postpone surgery based on the HbA_1c value, as I would if his glucose level were 600 mg/dL. Most of the studies that have assessed postoperative complications based on preoperative HbA_1c did not control for postoperative glucose levels. The incidence of complications varies based on the type of complication and the type of surgery.

Similarly, I would not use lipid values to guide management of this patient. Studies suggest that perioperative statin therapy may reduce postoperative morbidity and mortality in patients undergoing vascular surgery (see article by Poldermans on page S79 of this supplement), but our patient already has indications for a statin—a remote MI and diabetes—independent of what his lipid values are.

Question 2.2: How would you manage his elevated blood pressure (190/100 mm Hg)?

A. Discontinue metoprolol and start a different antihypertensive drug

B. Increase the metoprolol dose

C. Continue metoprolol and add a second drug

D. Observe him on his current regimen

Dr. Cohn: I would increase the dose of metoprolol and consider adding another drug, in view of his heart rate (90 beats per minute) and his cardiac status. Beta-blocker therapy should not be discontinued because doing so in the perioperative period is associated with an increased risk of adverse events such as cardiac death and MI.

Dr. Sweitzer: I would push up the metoprolol a bit to reduce the heart rate, knowing that beta-blockers are probably not the most efficacious antihypertensive agents. I would caution against starting an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) because he is scheduled to undergo a fairly significant procedure with expected blood loss and fluid shifts, and either of those agents in combination with a beta-blocker would be challenging to manage on the day of surgery.

Question 2.3: How would you manage his metformin perioperatively?

A. Discontinue it 48 hours preoperatively

B. Discontinue it 24 hours preoperatively

C. Withhold it on the morning of surgery

D. Continue it on the morning of surgery

Dr. Sweitzer: We routinely advise patients to hold all their oral diabetes medications the morning of surgery, primarily because many anesthesiologists are uncertain about the differing risks of hypoglycemia associated with the various oral agents.

Most of us will never see a patient who has lactic acidosis from metformin use. A systematic literature review and analysis found no increase in the risk of lactic acidosis with metformin compared with other oral hypoglycemics,⁶ so fear of lactic acidosis is not a valid reason to discontinue metformin. In fact, I think it is inappropriate to ever postpone or cancel surgery simply because the patient inadvertently took metformin on the morning of surgery. Some may argue that patients with renal insufficiency are at higher risk of lactic acidosis from metformin use on the morning of surgery, but keep in mind that renal insufficiency is a relative contra­indication to metformin use in the first place. Unless the patient is scheduled for a bilateral nephrectomy, his or her renal function is not going to be acutely reduced enough to enable a morning dose of metformin to cause lactic acidosis.

Dr. Cohn: Additionally, in a recent study of patients undergoing coronary artery bypass graft surgery (CABG), there was no increased risk of in-hospital morbidity or mortality in patients who received metformin on the morning of surgery,⁷ although I typically stop it 24 hours before major surgery.

Question 2.4: With respect to statin therapy, which course would you choose preoperatively?

A. Start a statin at a low dose

B. Start a statin at an intermediate dose

C. Start a statin at a high dose

D. Do not start a statin

Dr. Cohn: The answer to this question is not clear cut. The reason not to start a prophylactic statin would be the lack of evidence of benefit in patients undergoing noncardiac, nonvascular surgery, although there is evidence of potential benefit in patients undergoing vascular surgery.* The arguments in favor of starting a statin are that this patient has independent indications for a statin and the planned surgery is a high-risk procedure.

(* Editor’s note: In the time since this summit, results of the DECREASE-IV trial were published [Dunkelgrun et al, Ann Surg 2009; 249:921–926], showing a statisically nonsignificant trend toward improved outcomes at 30 days with fluvastatin in intermediate-risk patients undergoing noncardiovascular surgery.)

In cohort studies, perioperative death rates have been lower in statin recipients than in those not taking a statin.⁸ In the Dutch Echographic Cardiac Risk Evaluation Applying Stress Echo III (DECREASE III), which randomized noncardiac vascular surgery patients to perioperative fluvastatin or placebo, rates of MI and the composite end point of nonfatal MI or cardiovascular death were significantly lower in the statin group than in the placebo group.⁹

Question 2.5: Which of the following cardiac tests would you order preoperatively?

A. Exercise ECG

B. Dobutamine stress echocardiogram

C. Dipyridamole nuclear imaging

D. Coronary angiography

E. No further cardiac testing

Dr. Cohn: I wouldn’t do any cardiac testing since this patient needs surgery for his malignancy and the results of any testing would be highly unlikely to change management, in terms of canceling the surgery. This approach is consistent with the 2007 guidelines on perioperative cardiovascular evaluation for noncardiac surgery issued by the American College of Cardiology (ACC) and the American Heart Association (AHA).¹⁰

Dr. Sweitzer: I would differ on this question. This patient has not been evaluated adequately for his coronary artery disease. He has poor functional capacity that complicates assessment of his symptoms. He also has diabetes, so he is more likely to have silent myocardial ischemia. At age 78, he is understandably concerned about his survival: radical cystectomy is a major operation associated with significant blood loss, fluid shifts, and a long-term recuperative state. In this case, a cardiac evaluation may change management, not in terms of considering coronary revascularization before the surgery, but in terms of affecting the assessment of his chance of surviving this major operation, his life span following the operation, and his quality of life. For example, a highly positive dobutamine stress echo­cardiogram or certain wall motion abnormalities would suggest that he might not be protected even by optimal perioperative medical management.

Question 2.6: Which of the following would you do pre­operatively to assess pulmonary risk?

A. Obtain pulmonary function tests

B. Order a sleep study

C. Both

D. Neither

Dr. Sweitzer: There is no evidence supporting routine pulmonary function tests for patients undergoing procedures other than lung resection. If obstructive sleep apnea were suspected, I would order a sleep study only if I had access to one quickly to avoid delaying the surgery. Cancer surgery should never be delayed to get a sleep study. However, if this patient were seen in the primary care clinic, I would order a sleep study and, if indicated, put him on continuous positive airway pressure (CPAP). Whether or not preoperative CPAP makes a difference hasn’t been shown. No randomized controlled trials have been conducted, but there are some suggestions that the risks of ischemia and atrial arrhythmias in patients with known coronary artery disease can be reduced with CPAP. It is not always easy to initiate CPAP postoperatively because the number of CPAP machines is limited and titration by a respiratory technician is required, which is typically done in a sleep lab.

How the case was actually managed

Neither an HbA_1c measurement nor a lipid profile was ordered preoperatively, for lack of supportive evidence. The patient was continued on his beta-blocker and the dosage was increased sufficiently to control his blood pressure and heart rate. Metformin was continued, and statin therapy was begun preoperatively in light of the patient’s independent indications for it and the high-risk nature of the procedure. Stress testing was not ordered, in light of the lack of indication, given the patient’s stable angina. The patient refused a sleep study. The operation was lengthy and involved significant blood loss. The patient had a complicated postoperative course and ultimately died from multiorgan failure.

Scenario A: A 75-year-old man with diabetes, class III angina, and Q waves in inferior leads on his ECG is scheduled for elective femoropopliteal bypass surgery. His medications include isosorbide mononitrate (120 mg), amlodipine (10 mg), metoprolol controlled release (100 mg), atorvastatin (80 mg), insulin, and aspirin (81 mg). His heart rate is 64 beats per minute, blood pressure is controlled at 120/80 mm Hg, low-density lipoprotein cholesterol is 80 mg/dL, and creatinine is 1.5 μmol/L.

Scenario B: Consider the same patient undergoing elective cholecystectomy instead of a femoropopliteal bypass.

Scenario C: Consider the same patient scheduled for a cystoscopy instead of the other procedures. He had one episode of gross hematuria 1 week ago that resolved. Work-up by his urologist included a urinalysis and culture that were normal, cytology that was negative for malignancy, and a sonogram and computed tomography scan that were both negative. He has had no further bleeding and is not anemic. The urologist wants to do the cystoscopy for the sake of completeness.

Question 3.1: What would be your preoperative course of action in the above scenarios?

A. Order a dobutamine stress echocardiogram

B. Order nuclear imaging with dipyridamole or adenosine

C. Order coronary angiography

D. Order a resting two-dimensional echocardiogram

E. Continue his current medications and send to surgery with no further testing

Dr. Cohn: This is a man with an active cardiac condition and class III angina, which is considered severe angina in the ACC/AHA 2007 guidelines on peri­operative cardiac evaluation and care.¹⁰ The guidelines’ recommendation is to delay surgery for further evaluation and treatment. He is already on maximal medical therapy, which has failed to control his symptoms. He has poor exercise capacity. The only difference among the case scenarios is a variation in surgical risk.

This patient has independent indications for coronary angiography regardless of whether or not he’s undergoing surgery. He deserves evaluation for possible revascularization to improve his quality of life and symptoms.

I would send the patient to the catheterization lab in every one of these instances, with the possible exception of the cystoscopy scenario, where one could argue that revascularization with stenting would require antiplatelet therapy that might increase the bleeding risk, and also that the antiplatelet therapy would have to be interrupted for the cystoscopy, potentially increasing thrombotic risk.

Dr. Sweitzer: I disagree. The ACC/AHA 2007 guidelines do not recommend going directly to catheterization but rather recommend delaying surgery for further evaluation and treatment.¹⁰ We must ask whether this patient is truly receiving optimal medical management. After all, he is not on an ACE inhibitor or an ARB.

We must also consider whether the surgery is truly elective. In the first scenario, if he has peripheral vascular disease, he is likely to develop gangrene and have a further decrease in exercise capacity, which reduces his functional ability and increases his risk of comorbid conditions. He is at significant risk of developing worsening renal insufficiency or renal failure if he undergoes angiography. Coronary revascularization will delay treatment of his peripheral vascular disease. The Coronary Artery Revascularization Prophylaxis (CARP) trial showed no benefit of coronary revascularization relative to medical management in patients undergoing vascular surgery,¹¹ as is planned for this patient. I believe one must balance two competing risks and have an in-depth discussion with the patient.

In the second scenario, not treating gallstones or preventing cholelithiasis poses more risk to the health of this diabetic patient than does elective surgery if he needs a cholecystectomy. Emergency surgery, especially for acute cholecystitis, also significantly increases the risk of a cardiac event.

In the third scenario, the cystoscopy may uncover bladder cancer, which may be adversely affected by a delay of surgery. Regardless, the patient had gross hematuria and would be at risk for further bleeding should he undergo stenting with the requisite antiplatelet therapy.

Catheterization is not normally recommended unless CABG or stenting is being considered, yet I have seen no data that either of these procedures prolongs life except in very limited circumstances such as left main disease treated with bypass grafting. Though it is true that CABG reduces the incidence and severity of angina, it does not modify the physiologic cause of angina but rather may result in symptom improvement by damaging somatic nerve fibers to the heart. Putting a stent in this patient would be like applying a bandage: his symptoms will likely recur if he does not receive optimal medical management.

In a 2007 science advisory, several major medical societies cautioned against percutaneous coronary intervention (PCI) with drug-eluting stent placement in patients expected to undergo noncardiac surgery that would require interruption of antiplatelet therapy in the following 12 months (and against PCI with bare metal stent placement in patients undergoing such surgery in the following 4 to 6 weeks).¹² Therefore, I would not recommend catheterization for a patient whose noncardiac disease is likely to require surgery in the very near future, as is the case in each of the surgical scenarios above. One could consider noninvasive stress testing, which would be a safer approach and would almost certainly identify either significant stenosis of the left main coronary artery or three-vessel disease, which would be the only possible reasons to recommend CABG. I don’t believe there is any role for PCI for this patient.

Dr. Cohn: I argue for symptom relief even if it doesn’t prolong life. This patient cannot walk across the room without having symptoms despite taking multiple medications. I think he deserves a chance at revascularization if the angiogram shows he has a stenosis amenable to it, but I agree that a drug-eluting stent should not be placed if we know that he will undergo surgery within a few months.

A 60-year-old woman is scheduled for ventral hernia repair. Her medical history is unremarkable, with the exception of hypertension. She denies any bleeding problems and had no complications after a laparoscopic cholecystectomy 10 years ago. She has no family history of bleeding disorders.

Question 4.1: Would you order a prothrombin time (PT)/partial thromboplastin time (PTT)?

A. Yes

B. No

Dr. Cohn: I would not.

Dr. Sweitzer: I agree.

Question 4.2: Although not requested, a PT/PTT was ordered anyway. The PT is normal (12.2 sec/12 sec) and the PTT is abnormal (40 sec/25 sec). What is the most likely cause of the PTT abnormality?

A. Laboratory error

B. Factor VII deficiency

C. Factor IX deficiency

D. Factor XI deficiency

E. Factor XII deficiency

Dr. Cohn: The most likely cause is a sample with insufficient blood in the tube. The test wasn’t indicated in the first place, but now it must be done again.

Question 4.3: The PTT is repeated and remains abnormal: 42 sec/25 sec. Mixing studies correct the abnormality to 29 sec/25 sec. Based on this information, what is the most likely cause of the PTT abnormality?

A. Laboratory error

B. Lupus anticoagulant

C. Prekallikrein factor deficiency

D. Factor XII deficiency

Dr. Cohn: This is not a case of lupus anticoagulant because the abnormal PTT was corrected by the mixing study. Causes of a prolonged PTT include deficiencies of factors XII, XI, and IX, so factor XII deficiency is the most likely explanation, though a deficiency higher up the coagulation cascade (ie, prekallikrein factor deficiency) is possible. In the absence of any personal or family bleeding history, it is unlikely to be a deficiency of factors VII or IX (the hemophiliac) or of factor XI, so a deficiency of factor XII or one of the prekallikrein factors is more likely.

Dr. Sweitzer: A mixing study is indeed the appropriate first step. It is ordered from the lab and involves mixing the patient’s blood with normal plasma and incubating the mixture. If the mixture corrects the PTT result, as was the case with this patient, it indicates a coagulation factor deficiency in the patient’s blood; if it doesn’t correct, that should prompt evaluation for lupus anticoagulant or the presence of some other protein or hormone that’s prolonging the PTT.

Question 4.4: How would you manage this patient perioperatively?

A. Fresh frozen plasma

B. Platelet transfusion

C. Cryoprecipitate

D. Factor VII

E. No treatment necessary

Dr. Cohn: No treatment is necessary. Factor XII deficiency does not cause bleeding, regardless of the PTT. Factor XI deficiency is associated with bleeding, but usually there is a family history or a personal history of bleeding with surgery.

Screening coagulation studies are not usually indicated in a patient without a personal or family history of bleeding, liver disease, alcohol or drug use, or current anticoagulant therapy. Such studies are usually normal in such patients, and when they are not, it’s usually because of a lab error or a disease (hypercoagulable state) or factor deficiency that does not cause bleeding

Dr. Sweitzer: However, if the PTT is prolonged, the cause should be identified, because if the patient is sent to the operating room without an explanation for the prolongation, the perioperative team might think the patient has a bleeding problem and use fresh frozen plasma too readily. Fresh frozen plasma is not appropriate for everyone and may actually make a potentially hypercoagulable state worse.

Question from the audience: It was said that use of ACE inhibitors and ARBs should be avoided around the time of surgery. I’ve done an extensive literature search and found minimal to no evidence to support this practice. To the contrary, I found fairly good evidence to indicate that heart failure can be exacerbated significantly and acutely, as early as within 24 hours, when patients are taken off their ACE inhibitor or ARB. I would like your viewpoint on this basic pathology in perioperative medicine.

Dr. Cohn: The literature on the use of ACE inhibitors or ARBs prior to noncardiac surgery consists of five studies with fewer than 500 patients in total, as recently reviewed by Rosenman et al.¹³ Although there was no excess of death or MI associated with taking these medications on the morning of surgery, they did increase the need for fluid and pressors.

Dr. Sweitzer: Patients with hypertension have bigger variations of blood pressure, both hypo- and hypertension, in the perioperative period. For this reason, it was standard of care 30 years ago to stop all antihypertensive drugs, including beta-blockers, preoperatively. We soon found that although this practice prevented many episodes of hypotension, it increased the occurrence of perioperative hypertension and the likelihood of cardiac events. It then became standard of care to always continue antihypertensive drugs on the morning of surgery. In the late 1980s and early 1990s, several studies showed that ACE inhibitors and ARBs were associated with a more profound drop in blood pressure upon induction of general anesthesia compared with other antihypertensives.

The usual ways we treat drops in blood pressure—with phenylephrine and ephedrine—are not very effective in treating hypotension associated with general anesthesia in patients taking ACE inhibitors or ARBs. Vasopressin is effective in treating refractory hypotension during surgery, but anesthesiologists don’t use it often. Reducing the doses of induction agents is another means of attenuating the hypotension induced by ACE inhibitors and ARBs.

We should not routinely stop ACE inhibitors and ARBs on the day of surgery, particularly in patients being treated for heart failure, angina, or a prior MI. My bias is to selectively hold ACE inhibitors and ARBs on the morning of surgery in patients who are undergoing a significant operation with a high likelihood of hypotension, have well-controlled preoperative blood pressure, are taking multiple antihypertensive agents, and do not have heart failure. Otherwise, patients should continue their ACE inhibitors and ARBs on the morning of surgery, and the anesthesiologist should be prepared for significant hypotension upon induction of anesthesia, alter anesthesia induction doses accordingly, have vasopressin handy, and avoid the temptation to treat hypotension with fluids or repeated doses of phenylephrine and ephedrine. The previous comment about concerns with ACE inhibitors and ARBs was in the context of initiating new therapies in the immediate preoperative period.

Question from the audience: Urinalysis is ordered for many patients undergoing orthopedic surgery, and invariably some bacteriuria is found. Can you comment on the value of urinalysis and subsequent treatment of abnormal results?

Dr. Cohn: I believe you should never order a urinalysis in an asymptomatic patient, with the exception of patients undergoing procedures that involve genitourinary or gynecologic instrumentation. Ordering a urinalysis before joint replacement has been promoted in the orthopedic literature on the theoretical grounds that bacteria might somehow seed and colonize the joint. Orthopedic surgeons like to do it, but I disregard their requests for it.

Dr. Sweitzer: One study showed that we’d need to spend $1.5 million on screening urinalysis for asymptomatic patients scheduled for joint replacement surgery in order to prevent one joint infection.¹⁴

Dr. Cohn: Also, patients are going to get their one dose of cephalosporin before surgery anyway, and that will probably knock out any bacteria that would be found on urinalysis.

Question from the audience: Can you clarify how the 2007 ACC/AHA perioperative guidelines define an active cardiac condition? The patient in your third case report had class III angina, or angina with less than usual activities, but nothing was presented to suggest that his symptoms were unstable. I would suggest that despite his class III symptoms, his angina was stable, and I would have continued down the algorithm rather than defining his cardiac condition as active and considering an intervention.

Dr. Cohn: An active cardiac condition is defined by the ACC as unstable coronary syndromes, which include acute (within the prior 7 days) or recent (within the prior 30 days) MI, unstable angina, and severe (class III or IV) angina.

CASE 1: RADICAL PROSTATECTOMY IN A MAN WITH ACUTE DEEP VEIN THROMBOSIS

A 69-year-old man is seen in the preoperative clinic 1 week before a scheduled radical prostatectomy. He has been diagnosed with femoral deep vein thrombosis (DVT) following a complaint of calf soreness.

Question 1.1: How would you treat him for his DVT?

A. Intravenous (IV) unfractionated heparin (UFH)

B. Low-molecular-weight heparin (LMWH)

C. Inferior vena cava (IVC) filter

D. Combination of pharmacologic therapy and then an IVC filter

Dr. Steven L. Cohn: The latest edition of the American College of Chest Physicians (ACCP) evidence-based guidelines on antithrombotic therapy recommends the use of therapeutic-dose subcutaneous LMWH over IV UFH for initial treatment of acute DVT in the outpatient or inpatient setting.¹ Additionally, indications for an IVC filter include the prevention of pulmonary embolism (PE) in a patient with DVT who requires full-dose anticoagulation but cannot receive it, as would be the case here if the patient proceeds with surgery as scheduled. So if surgery will be postponed, the best option is LMWH; if surgery will not be postponed, the best answer is a combination of pharmacologic therapy with low-dose LMWH and an IVC filter, preferably a retrievable one.²

Question 1.2: You recommend postponing surgery, but the patient is worried about metastatic disease. For how long should surgery be postponed?

A. 2 weeks

B. 1 month

C. 2 months

D. 3 months

E. 6 months

Dr. Cohn: In the absence of anticoagulation therapy, the risk of venous thromboembolism (VTE) is approximately 40% (~1% per day) during the first month following an acute VTE and then declines markedly, to approximately 10%, during the second and third months following the acute event.³ Therefore, I would suggest that the patient wait at least 1 month after an acute DVT before undergoing surgery.

Dr. BobbieJean Sweitzer: This patient is in a hypercoagulable state, and the surgery itself will induce excess hypercoagulability. With a femoral DVT already present, his risk of VTE or PE is likely to be greater than 1% per day during the first month. If he does develop a PE, it may potentially be fatal.

Question 1.3: According to the patient, the surgeon and the internist discussed options, but the surgeon “doesn’t believe in filters” and the patient doesn’t want to postpone the procedure, despite your recommendation. Two weeks later he shows up for surgery having stopped his LMWH 3 days before. What would you do?

A. Cancel the surgery and restart full-dose LMWH

B. Proceed with prophylactic-dose LMWH

C. Proceed after giving a full therapeutic dose

D. Insert a filter and give DVT prophylaxis

Dr. Cohn: A bridging protocol should have been discussed with the surgeon and anesthesiologist before the procedure. Therapeutic levels of LMWH persist as long as 18 hours after discontinuation; therefore, the ACCP recommends interrupting LMWH 24 hours before surgery.⁴

Dr. Sweitzer: The lack of a bridging protocol in this case created a problem. The patient was afraid to continue anticoagulation after hearing the internist and surgeon disagree about the plan, and thus stopped it entirely, and he did not want to delay surgery because he was fearful of metastasis. The surgeon was adamant that IVC filters don’t work. The internist was concerned that the patient was at high risk for a PE. Even though the documented risk of postponing radical prostatectomy for a short time is inconsequential, I was convinced that the patient would not believe this if metastasis were to develop in the future.

Question 1.4: How would you have managed his anticoagulation perioperatively?

A. Stop LMWH 12 hours before surgery and restart at full dose 12 to 24 hours after surgery

B. Stop LMWH 24 hours before surgery and restart at full dose 24 hours after surgery

C. Stop LMWH 24 hours before surgery and restart prophylactic dosing 12 to 24 hours after surgery, and then full-dose LMWH in 48 to 72 hours

D. Stop LMWH 24 hours before surgery and restart at full dose 72 hours after surgery

Dr. Cohn: The correct timing for stopping LMWH is 24 hours before surgery. As for how to resume anticoagulation in patients at high risk for VTE or those undergoing major surgery, the latest ACCP guidelines recommend the following⁴:

• Reinitiation of anticoagulation 12 to 24 hours postoperatively, assuming adequate hemostasis in patients not at high risk for bleeding
• Use of a prophylactic dose or no anticoagulation for up to 72 hours if the patient is at high risk for bleeding.

These recommendations are a departure from previous practice, in which we routinely restarted anticoagulation 6 to 12 hours postoperatively.

Dr. Sweitzer: According to guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA),⁵ if twice-daily LMWH is stopped 24 hours ahead of time (as long as patients have normal renal function), it is safe to perform epidural or spinal anesthesia, if either is an option. If full-dose UFH is used, the partial thrombo­plastin time (PTT) is monitored and central neuraxial blockade may be done if the PTT is in the normal range, which typically is 2 to 6 hours after UFH is stopped.

Additionally, the platelet count should be checked every 3 days postoperatively while the patient is on UFH or LMWH. It may be just as important to monitor the platelet count preoperatively if the patient has been on UFH or LMWH for an extended duration, especially if a central neuraxial anesthetic technique is planned.

Dr. Cohn: The reason for monitoring the platelet count is the potential for heparin-induced thrombocytopenia in patients on UFH. I recently encountered a patient who developed postoperative heparin-induced thrombo­cytopenia with thrombosis while on LMWH, which is relatively uncommon compared with UFH.

Case resolution

After much discussion of the risk of a significant PE with the patient, family, urologist, and vascular surgeon, it is decided that a temporary IVC filter will be placed in the operating room immediately after induction of general anesthesia and before the prostatectomy. The operation is delayed about 1 hour to allow this option. The patient is successfully treated and has the IVC filter removed 1 month postoperatively.

A 78-year-old obese Russian-speaking man is seen in the preoperative clinic prior to a scheduled radical cystectomy for highly invasive bladder cancer. He is a poor historian and argues with the several family members accompanying him, but it is determined that his medical history includes hypertension, diabetes mellitus, a myocardial infarction (MI) 5 years previously (in Russia), and stable angina that is determined to be class II.

He had no previous work-up and no electrocardiogram (ECG). His medications are aspirin, metoprolol, and metformin. His blood pressure is 190/100 mm Hg, heart rate 90 beats per minute, and body mass index 32. On examination, there is no murmur, S3 gallop, or rales. His blood glucose is 220 mg/dL, and his creatinine is slightly elevated (1.4 mg/dL). ECG verifies a prior MI.

Question 2.1: Which of the following additional tests should be ordered preoperatively?

A. Hemoglobin (Hb) A_1c

B. Lipid profile

C. Both

D. Neither

Dr. Sweitzer: Because the surgery is not elective, no immediate benefit would be achieved by ordering either an HbA_1c or a lipid profile. However, if you view the preoperative evaluation as an opportunity to manage risk factors over the long term, then it may be a good idea to order the lipid profile because this patient has rarely engaged the health care system. Likewise, the HbA_1c can be ordered to set in place his long-term management. Sometimes we focus on the preoperative visit only in the context of the surgery, but if a test or intervention is appropriate and needed for long-term management, then it is appropriate to do now.

Dr. Cohn: There is no evidence to support using the preoperative HbA_1c to alter management decisions. I would not postpone surgery based on the HbA_1c value, as I would if his glucose level were 600 mg/dL. Most of the studies that have assessed postoperative complications based on preoperative HbA_1c did not control for postoperative glucose levels. The incidence of complications varies based on the type of complication and the type of surgery.

Similarly, I would not use lipid values to guide management of this patient. Studies suggest that perioperative statin therapy may reduce postoperative morbidity and mortality in patients undergoing vascular surgery (see article by Poldermans on page S79 of this supplement), but our patient already has indications for a statin—a remote MI and diabetes—independent of what his lipid values are.

Question 2.2: How would you manage his elevated blood pressure (190/100 mm Hg)?

A. Discontinue metoprolol and start a different antihypertensive drug

B. Increase the metoprolol dose

C. Continue metoprolol and add a second drug

D. Observe him on his current regimen

Dr. Cohn: I would increase the dose of metoprolol and consider adding another drug, in view of his heart rate (90 beats per minute) and his cardiac status. Beta-blocker therapy should not be discontinued because doing so in the perioperative period is associated with an increased risk of adverse events such as cardiac death and MI.

Dr. Sweitzer: I would push up the metoprolol a bit to reduce the heart rate, knowing that beta-blockers are probably not the most efficacious antihypertensive agents. I would caution against starting an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) because he is scheduled to undergo a fairly significant procedure with expected blood loss and fluid shifts, and either of those agents in combination with a beta-blocker would be challenging to manage on the day of surgery.

Question 2.3: How would you manage his metformin perioperatively?

A. Discontinue it 48 hours preoperatively

B. Discontinue it 24 hours preoperatively

C. Withhold it on the morning of surgery

D. Continue it on the morning of surgery

Dr. Sweitzer: We routinely advise patients to hold all their oral diabetes medications the morning of surgery, primarily because many anesthesiologists are uncertain about the differing risks of hypoglycemia associated with the various oral agents.

Most of us will never see a patient who has lactic acidosis from metformin use. A systematic literature review and analysis found no increase in the risk of lactic acidosis with metformin compared with other oral hypoglycemics,⁶ so fear of lactic acidosis is not a valid reason to discontinue metformin. In fact, I think it is inappropriate to ever postpone or cancel surgery simply because the patient inadvertently took metformin on the morning of surgery. Some may argue that patients with renal insufficiency are at higher risk of lactic acidosis from metformin use on the morning of surgery, but keep in mind that renal insufficiency is a relative contra­indication to metformin use in the first place. Unless the patient is scheduled for a bilateral nephrectomy, his or her renal function is not going to be acutely reduced enough to enable a morning dose of metformin to cause lactic acidosis.

Dr. Cohn: Additionally, in a recent study of patients undergoing coronary artery bypass graft surgery (CABG), there was no increased risk of in-hospital morbidity or mortality in patients who received metformin on the morning of surgery,⁷ although I typically stop it 24 hours before major surgery.

Question 2.4: With respect to statin therapy, which course would you choose preoperatively?

A. Start a statin at a low dose

B. Start a statin at an intermediate dose

C. Start a statin at a high dose

D. Do not start a statin

Dr. Cohn: The answer to this question is not clear cut. The reason not to start a prophylactic statin would be the lack of evidence of benefit in patients undergoing noncardiac, nonvascular surgery, although there is evidence of potential benefit in patients undergoing vascular surgery.* The arguments in favor of starting a statin are that this patient has independent indications for a statin and the planned surgery is a high-risk procedure.

(* Editor’s note: In the time since this summit, results of the DECREASE-IV trial were published [Dunkelgrun et al, Ann Surg 2009; 249:921–926], showing a statisically nonsignificant trend toward improved outcomes at 30 days with fluvastatin in intermediate-risk patients undergoing noncardiovascular surgery.)

In cohort studies, perioperative death rates have been lower in statin recipients than in those not taking a statin.⁸ In the Dutch Echographic Cardiac Risk Evaluation Applying Stress Echo III (DECREASE III), which randomized noncardiac vascular surgery patients to perioperative fluvastatin or placebo, rates of MI and the composite end point of nonfatal MI or cardiovascular death were significantly lower in the statin group than in the placebo group.⁹

Question 2.5: Which of the following cardiac tests would you order preoperatively?

A. Exercise ECG

B. Dobutamine stress echocardiogram

C. Dipyridamole nuclear imaging

D. Coronary angiography

E. No further cardiac testing

Dr. Cohn: I wouldn’t do any cardiac testing since this patient needs surgery for his malignancy and the results of any testing would be highly unlikely to change management, in terms of canceling the surgery. This approach is consistent with the 2007 guidelines on perioperative cardiovascular evaluation for noncardiac surgery issued by the American College of Cardiology (ACC) and the American Heart Association (AHA).¹⁰

Dr. Sweitzer: I would differ on this question. This patient has not been evaluated adequately for his coronary artery disease. He has poor functional capacity that complicates assessment of his symptoms. He also has diabetes, so he is more likely to have silent myocardial ischemia. At age 78, he is understandably concerned about his survival: radical cystectomy is a major operation associated with significant blood loss, fluid shifts, and a long-term recuperative state. In this case, a cardiac evaluation may change management, not in terms of considering coronary revascularization before the surgery, but in terms of affecting the assessment of his chance of surviving this major operation, his life span following the operation, and his quality of life. For example, a highly positive dobutamine stress echo­cardiogram or certain wall motion abnormalities would suggest that he might not be protected even by optimal perioperative medical management.

Question 2.6: Which of the following would you do pre­operatively to assess pulmonary risk?

A. Obtain pulmonary function tests

B. Order a sleep study

C. Both

D. Neither

Dr. Sweitzer: There is no evidence supporting routine pulmonary function tests for patients undergoing procedures other than lung resection. If obstructive sleep apnea were suspected, I would order a sleep study only if I had access to one quickly to avoid delaying the surgery. Cancer surgery should never be delayed to get a sleep study. However, if this patient were seen in the primary care clinic, I would order a sleep study and, if indicated, put him on continuous positive airway pressure (CPAP). Whether or not preoperative CPAP makes a difference hasn’t been shown. No randomized controlled trials have been conducted, but there are some suggestions that the risks of ischemia and atrial arrhythmias in patients with known coronary artery disease can be reduced with CPAP. It is not always easy to initiate CPAP postoperatively because the number of CPAP machines is limited and titration by a respiratory technician is required, which is typically done in a sleep lab.

How the case was actually managed

Neither an HbA_1c measurement nor a lipid profile was ordered preoperatively, for lack of supportive evidence. The patient was continued on his beta-blocker and the dosage was increased sufficiently to control his blood pressure and heart rate. Metformin was continued, and statin therapy was begun preoperatively in light of the patient’s independent indications for it and the high-risk nature of the procedure. Stress testing was not ordered, in light of the lack of indication, given the patient’s stable angina. The patient refused a sleep study. The operation was lengthy and involved significant blood loss. The patient had a complicated postoperative course and ultimately died from multiorgan failure.

Scenario A: A 75-year-old man with diabetes, class III angina, and Q waves in inferior leads on his ECG is scheduled for elective femoropopliteal bypass surgery. His medications include isosorbide mononitrate (120 mg), amlodipine (10 mg), metoprolol controlled release (100 mg), atorvastatin (80 mg), insulin, and aspirin (81 mg). His heart rate is 64 beats per minute, blood pressure is controlled at 120/80 mm Hg, low-density lipoprotein cholesterol is 80 mg/dL, and creatinine is 1.5 μmol/L.

Scenario B: Consider the same patient undergoing elective cholecystectomy instead of a femoropopliteal bypass.

Scenario C: Consider the same patient scheduled for a cystoscopy instead of the other procedures. He had one episode of gross hematuria 1 week ago that resolved. Work-up by his urologist included a urinalysis and culture that were normal, cytology that was negative for malignancy, and a sonogram and computed tomography scan that were both negative. He has had no further bleeding and is not anemic. The urologist wants to do the cystoscopy for the sake of completeness.

Question 3.1: What would be your preoperative course of action in the above scenarios?

A. Order a dobutamine stress echocardiogram

B. Order nuclear imaging with dipyridamole or adenosine

C. Order coronary angiography

D. Order a resting two-dimensional echocardiogram

E. Continue his current medications and send to surgery with no further testing

Dr. Cohn: This is a man with an active cardiac condition and class III angina, which is considered severe angina in the ACC/AHA 2007 guidelines on peri­operative cardiac evaluation and care.¹⁰ The guidelines’ recommendation is to delay surgery for further evaluation and treatment. He is already on maximal medical therapy, which has failed to control his symptoms. He has poor exercise capacity. The only difference among the case scenarios is a variation in surgical risk.

This patient has independent indications for coronary angiography regardless of whether or not he’s undergoing surgery. He deserves evaluation for possible revascularization to improve his quality of life and symptoms.

I would send the patient to the catheterization lab in every one of these instances, with the possible exception of the cystoscopy scenario, where one could argue that revascularization with stenting would require antiplatelet therapy that might increase the bleeding risk, and also that the antiplatelet therapy would have to be interrupted for the cystoscopy, potentially increasing thrombotic risk.

Dr. Sweitzer: I disagree. The ACC/AHA 2007 guidelines do not recommend going directly to catheterization but rather recommend delaying surgery for further evaluation and treatment.¹⁰ We must ask whether this patient is truly receiving optimal medical management. After all, he is not on an ACE inhibitor or an ARB.

We must also consider whether the surgery is truly elective. In the first scenario, if he has peripheral vascular disease, he is likely to develop gangrene and have a further decrease in exercise capacity, which reduces his functional ability and increases his risk of comorbid conditions. He is at significant risk of developing worsening renal insufficiency or renal failure if he undergoes angiography. Coronary revascularization will delay treatment of his peripheral vascular disease. The Coronary Artery Revascularization Prophylaxis (CARP) trial showed no benefit of coronary revascularization relative to medical management in patients undergoing vascular surgery,¹¹ as is planned for this patient. I believe one must balance two competing risks and have an in-depth discussion with the patient.

In the second scenario, not treating gallstones or preventing cholelithiasis poses more risk to the health of this diabetic patient than does elective surgery if he needs a cholecystectomy. Emergency surgery, especially for acute cholecystitis, also significantly increases the risk of a cardiac event.

In the third scenario, the cystoscopy may uncover bladder cancer, which may be adversely affected by a delay of surgery. Regardless, the patient had gross hematuria and would be at risk for further bleeding should he undergo stenting with the requisite antiplatelet therapy.

Catheterization is not normally recommended unless CABG or stenting is being considered, yet I have seen no data that either of these procedures prolongs life except in very limited circumstances such as left main disease treated with bypass grafting. Though it is true that CABG reduces the incidence and severity of angina, it does not modify the physiologic cause of angina but rather may result in symptom improvement by damaging somatic nerve fibers to the heart. Putting a stent in this patient would be like applying a bandage: his symptoms will likely recur if he does not receive optimal medical management.

In a 2007 science advisory, several major medical societies cautioned against percutaneous coronary intervention (PCI) with drug-eluting stent placement in patients expected to undergo noncardiac surgery that would require interruption of antiplatelet therapy in the following 12 months (and against PCI with bare metal stent placement in patients undergoing such surgery in the following 4 to 6 weeks).¹² Therefore, I would not recommend catheterization for a patient whose noncardiac disease is likely to require surgery in the very near future, as is the case in each of the surgical scenarios above. One could consider noninvasive stress testing, which would be a safer approach and would almost certainly identify either significant stenosis of the left main coronary artery or three-vessel disease, which would be the only possible reasons to recommend CABG. I don’t believe there is any role for PCI for this patient.

Dr. Cohn: I argue for symptom relief even if it doesn’t prolong life. This patient cannot walk across the room without having symptoms despite taking multiple medications. I think he deserves a chance at revascularization if the angiogram shows he has a stenosis amenable to it, but I agree that a drug-eluting stent should not be placed if we know that he will undergo surgery within a few months.

A 60-year-old woman is scheduled for ventral hernia repair. Her medical history is unremarkable, with the exception of hypertension. She denies any bleeding problems and had no complications after a laparoscopic cholecystectomy 10 years ago. She has no family history of bleeding disorders.

Question 4.1: Would you order a prothrombin time (PT)/partial thromboplastin time (PTT)?

A. Yes

B. No

Dr. Cohn: I would not.

Dr. Sweitzer: I agree.

Question 4.2: Although not requested, a PT/PTT was ordered anyway. The PT is normal (12.2 sec/12 sec) and the PTT is abnormal (40 sec/25 sec). What is the most likely cause of the PTT abnormality?

A. Laboratory error

B. Factor VII deficiency

C. Factor IX deficiency

D. Factor XI deficiency

E. Factor XII deficiency

Dr. Cohn: The most likely cause is a sample with insufficient blood in the tube. The test wasn’t indicated in the first place, but now it must be done again.

Question 4.3: The PTT is repeated and remains abnormal: 42 sec/25 sec. Mixing studies correct the abnormality to 29 sec/25 sec. Based on this information, what is the most likely cause of the PTT abnormality?

A. Laboratory error

B. Lupus anticoagulant

C. Prekallikrein factor deficiency

D. Factor XII deficiency

Dr. Cohn: This is not a case of lupus anticoagulant because the abnormal PTT was corrected by the mixing study. Causes of a prolonged PTT include deficiencies of factors XII, XI, and IX, so factor XII deficiency is the most likely explanation, though a deficiency higher up the coagulation cascade (ie, prekallikrein factor deficiency) is possible. In the absence of any personal or family bleeding history, it is unlikely to be a deficiency of factors VII or IX (the hemophiliac) or of factor XI, so a deficiency of factor XII or one of the prekallikrein factors is more likely.

Dr. Sweitzer: A mixing study is indeed the appropriate first step. It is ordered from the lab and involves mixing the patient’s blood with normal plasma and incubating the mixture. If the mixture corrects the PTT result, as was the case with this patient, it indicates a coagulation factor deficiency in the patient’s blood; if it doesn’t correct, that should prompt evaluation for lupus anticoagulant or the presence of some other protein or hormone that’s prolonging the PTT.

Question 4.4: How would you manage this patient perioperatively?

A. Fresh frozen plasma

B. Platelet transfusion

C. Cryoprecipitate

D. Factor VII

E. No treatment necessary

Dr. Cohn: No treatment is necessary. Factor XII deficiency does not cause bleeding, regardless of the PTT. Factor XI deficiency is associated with bleeding, but usually there is a family history or a personal history of bleeding with surgery.

Screening coagulation studies are not usually indicated in a patient without a personal or family history of bleeding, liver disease, alcohol or drug use, or current anticoagulant therapy. Such studies are usually normal in such patients, and when they are not, it’s usually because of a lab error or a disease (hypercoagulable state) or factor deficiency that does not cause bleeding

Dr. Sweitzer: However, if the PTT is prolonged, the cause should be identified, because if the patient is sent to the operating room without an explanation for the prolongation, the perioperative team might think the patient has a bleeding problem and use fresh frozen plasma too readily. Fresh frozen plasma is not appropriate for everyone and may actually make a potentially hypercoagulable state worse.

Question from the audience: It was said that use of ACE inhibitors and ARBs should be avoided around the time of surgery. I’ve done an extensive literature search and found minimal to no evidence to support this practice. To the contrary, I found fairly good evidence to indicate that heart failure can be exacerbated significantly and acutely, as early as within 24 hours, when patients are taken off their ACE inhibitor or ARB. I would like your viewpoint on this basic pathology in perioperative medicine.

Dr. Cohn: The literature on the use of ACE inhibitors or ARBs prior to noncardiac surgery consists of five studies with fewer than 500 patients in total, as recently reviewed by Rosenman et al.¹³ Although there was no excess of death or MI associated with taking these medications on the morning of surgery, they did increase the need for fluid and pressors.

Dr. Sweitzer: Patients with hypertension have bigger variations of blood pressure, both hypo- and hypertension, in the perioperative period. For this reason, it was standard of care 30 years ago to stop all antihypertensive drugs, including beta-blockers, preoperatively. We soon found that although this practice prevented many episodes of hypotension, it increased the occurrence of perioperative hypertension and the likelihood of cardiac events. It then became standard of care to always continue antihypertensive drugs on the morning of surgery. In the late 1980s and early 1990s, several studies showed that ACE inhibitors and ARBs were associated with a more profound drop in blood pressure upon induction of general anesthesia compared with other antihypertensives.

The usual ways we treat drops in blood pressure—with phenylephrine and ephedrine—are not very effective in treating hypotension associated with general anesthesia in patients taking ACE inhibitors or ARBs. Vasopressin is effective in treating refractory hypotension during surgery, but anesthesiologists don’t use it often. Reducing the doses of induction agents is another means of attenuating the hypotension induced by ACE inhibitors and ARBs.

We should not routinely stop ACE inhibitors and ARBs on the day of surgery, particularly in patients being treated for heart failure, angina, or a prior MI. My bias is to selectively hold ACE inhibitors and ARBs on the morning of surgery in patients who are undergoing a significant operation with a high likelihood of hypotension, have well-controlled preoperative blood pressure, are taking multiple antihypertensive agents, and do not have heart failure. Otherwise, patients should continue their ACE inhibitors and ARBs on the morning of surgery, and the anesthesiologist should be prepared for significant hypotension upon induction of anesthesia, alter anesthesia induction doses accordingly, have vasopressin handy, and avoid the temptation to treat hypotension with fluids or repeated doses of phenylephrine and ephedrine. The previous comment about concerns with ACE inhibitors and ARBs was in the context of initiating new therapies in the immediate preoperative period.

Question from the audience: Urinalysis is ordered for many patients undergoing orthopedic surgery, and invariably some bacteriuria is found. Can you comment on the value of urinalysis and subsequent treatment of abnormal results?

Dr. Cohn: I believe you should never order a urinalysis in an asymptomatic patient, with the exception of patients undergoing procedures that involve genitourinary or gynecologic instrumentation. Ordering a urinalysis before joint replacement has been promoted in the orthopedic literature on the theoretical grounds that bacteria might somehow seed and colonize the joint. Orthopedic surgeons like to do it, but I disregard their requests for it.

Dr. Sweitzer: One study showed that we’d need to spend $1.5 million on screening urinalysis for asymptomatic patients scheduled for joint replacement surgery in order to prevent one joint infection.¹⁴

Dr. Cohn: Also, patients are going to get their one dose of cephalosporin before surgery anyway, and that will probably knock out any bacteria that would be found on urinalysis.

Question from the audience: Can you clarify how the 2007 ACC/AHA perioperative guidelines define an active cardiac condition? The patient in your third case report had class III angina, or angina with less than usual activities, but nothing was presented to suggest that his symptoms were unstable. I would suggest that despite his class III symptoms, his angina was stable, and I would have continued down the algorithm rather than defining his cardiac condition as active and considering an intervention.

Dr. Cohn: An active cardiac condition is defined by the ACC as unstable coronary syndromes, which include acute (within the prior 7 days) or recent (within the prior 30 days) MI, unstable angina, and severe (class III or IV) angina.

CASE 1: RADICAL PROSTATECTOMY IN A MAN WITH ACUTE DEEP VEIN THROMBOSIS

A 69-year-old man is seen in the preoperative clinic 1 week before a scheduled radical prostatectomy. He has been diagnosed with femoral deep vein thrombosis (DVT) following a complaint of calf soreness.

Question 1.1: How would you treat him for his DVT?

A. Intravenous (IV) unfractionated heparin (UFH)

B. Low-molecular-weight heparin (LMWH)

C. Inferior vena cava (IVC) filter

D. Combination of pharmacologic therapy and then an IVC filter

Dr. Steven L. Cohn: The latest edition of the American College of Chest Physicians (ACCP) evidence-based guidelines on antithrombotic therapy recommends the use of therapeutic-dose subcutaneous LMWH over IV UFH for initial treatment of acute DVT in the outpatient or inpatient setting.¹ Additionally, indications for an IVC filter include the prevention of pulmonary embolism (PE) in a patient with DVT who requires full-dose anticoagulation but cannot receive it, as would be the case here if the patient proceeds with surgery as scheduled. So if surgery will be postponed, the best option is LMWH; if surgery will not be postponed, the best answer is a combination of pharmacologic therapy with low-dose LMWH and an IVC filter, preferably a retrievable one.²

Question 1.2: You recommend postponing surgery, but the patient is worried about metastatic disease. For how long should surgery be postponed?

A. 2 weeks

B. 1 month

C. 2 months

D. 3 months

E. 6 months

Dr. Cohn: In the absence of anticoagulation therapy, the risk of venous thromboembolism (VTE) is approximately 40% (~1% per day) during the first month following an acute VTE and then declines markedly, to approximately 10%, during the second and third months following the acute event.³ Therefore, I would suggest that the patient wait at least 1 month after an acute DVT before undergoing surgery.

Dr. BobbieJean Sweitzer: This patient is in a hypercoagulable state, and the surgery itself will induce excess hypercoagulability. With a femoral DVT already present, his risk of VTE or PE is likely to be greater than 1% per day during the first month. If he does develop a PE, it may potentially be fatal.

Question 1.3: According to the patient, the surgeon and the internist discussed options, but the surgeon “doesn’t believe in filters” and the patient doesn’t want to postpone the procedure, despite your recommendation. Two weeks later he shows up for surgery having stopped his LMWH 3 days before. What would you do?

A. Cancel the surgery and restart full-dose LMWH

B. Proceed with prophylactic-dose LMWH

C. Proceed after giving a full therapeutic dose

D. Insert a filter and give DVT prophylaxis

Dr. Cohn: A bridging protocol should have been discussed with the surgeon and anesthesiologist before the procedure. Therapeutic levels of LMWH persist as long as 18 hours after discontinuation; therefore, the ACCP recommends interrupting LMWH 24 hours before surgery.⁴

Dr. Sweitzer: The lack of a bridging protocol in this case created a problem. The patient was afraid to continue anticoagulation after hearing the internist and surgeon disagree about the plan, and thus stopped it entirely, and he did not want to delay surgery because he was fearful of metastasis. The surgeon was adamant that IVC filters don’t work. The internist was concerned that the patient was at high risk for a PE. Even though the documented risk of postponing radical prostatectomy for a short time is inconsequential, I was convinced that the patient would not believe this if metastasis were to develop in the future.

Question 1.4: How would you have managed his anticoagulation perioperatively?

A. Stop LMWH 12 hours before surgery and restart at full dose 12 to 24 hours after surgery

B. Stop LMWH 24 hours before surgery and restart at full dose 24 hours after surgery

C. Stop LMWH 24 hours before surgery and restart prophylactic dosing 12 to 24 hours after surgery, and then full-dose LMWH in 48 to 72 hours

D. Stop LMWH 24 hours before surgery and restart at full dose 72 hours after surgery

Dr. Cohn: The correct timing for stopping LMWH is 24 hours before surgery. As for how to resume anticoagulation in patients at high risk for VTE or those undergoing major surgery, the latest ACCP guidelines recommend the following⁴:

• Reinitiation of anticoagulation 12 to 24 hours postoperatively, assuming adequate hemostasis in patients not at high risk for bleeding
• Use of a prophylactic dose or no anticoagulation for up to 72 hours if the patient is at high risk for bleeding.

These recommendations are a departure from previous practice, in which we routinely restarted anticoagulation 6 to 12 hours postoperatively.

Dr. Sweitzer: According to guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA),⁵ if twice-daily LMWH is stopped 24 hours ahead of time (as long as patients have normal renal function), it is safe to perform epidural or spinal anesthesia, if either is an option. If full-dose UFH is used, the partial thrombo­plastin time (PTT) is monitored and central neuraxial blockade may be done if the PTT is in the normal range, which typically is 2 to 6 hours after UFH is stopped.

Additionally, the platelet count should be checked every 3 days postoperatively while the patient is on UFH or LMWH. It may be just as important to monitor the platelet count preoperatively if the patient has been on UFH or LMWH for an extended duration, especially if a central neuraxial anesthetic technique is planned.

Dr. Cohn: The reason for monitoring the platelet count is the potential for heparin-induced thrombocytopenia in patients on UFH. I recently encountered a patient who developed postoperative heparin-induced thrombo­cytopenia with thrombosis while on LMWH, which is relatively uncommon compared with UFH.

Case resolution

After much discussion of the risk of a significant PE with the patient, family, urologist, and vascular surgeon, it is decided that a temporary IVC filter will be placed in the operating room immediately after induction of general anesthesia and before the prostatectomy. The operation is delayed about 1 hour to allow this option. The patient is successfully treated and has the IVC filter removed 1 month postoperatively.

A 78-year-old obese Russian-speaking man is seen in the preoperative clinic prior to a scheduled radical cystectomy for highly invasive bladder cancer. He is a poor historian and argues with the several family members accompanying him, but it is determined that his medical history includes hypertension, diabetes mellitus, a myocardial infarction (MI) 5 years previously (in Russia), and stable angina that is determined to be class II.

He had no previous work-up and no electrocardiogram (ECG). His medications are aspirin, metoprolol, and metformin. His blood pressure is 190/100 mm Hg, heart rate 90 beats per minute, and body mass index 32. On examination, there is no murmur, S3 gallop, or rales. His blood glucose is 220 mg/dL, and his creatinine is slightly elevated (1.4 mg/dL). ECG verifies a prior MI.

Question 2.1: Which of the following additional tests should be ordered preoperatively?

A. Hemoglobin (Hb) A_1c

B. Lipid profile

C. Both

D. Neither

Dr. Sweitzer: Because the surgery is not elective, no immediate benefit would be achieved by ordering either an HbA_1c or a lipid profile. However, if you view the preoperative evaluation as an opportunity to manage risk factors over the long term, then it may be a good idea to order the lipid profile because this patient has rarely engaged the health care system. Likewise, the HbA_1c can be ordered to set in place his long-term management. Sometimes we focus on the preoperative visit only in the context of the surgery, but if a test or intervention is appropriate and needed for long-term management, then it is appropriate to do now.

Dr. Cohn: There is no evidence to support using the preoperative HbA_1c to alter management decisions. I would not postpone surgery based on the HbA_1c value, as I would if his glucose level were 600 mg/dL. Most of the studies that have assessed postoperative complications based on preoperative HbA_1c did not control for postoperative glucose levels. The incidence of complications varies based on the type of complication and the type of surgery.

Similarly, I would not use lipid values to guide management of this patient. Studies suggest that perioperative statin therapy may reduce postoperative morbidity and mortality in patients undergoing vascular surgery (see article by Poldermans on page S79 of this supplement), but our patient already has indications for a statin—a remote MI and diabetes—independent of what his lipid values are.

Question 2.2: How would you manage his elevated blood pressure (190/100 mm Hg)?

A. Discontinue metoprolol and start a different antihypertensive drug

B. Increase the metoprolol dose

C. Continue metoprolol and add a second drug

D. Observe him on his current regimen

Dr. Cohn: I would increase the dose of metoprolol and consider adding another drug, in view of his heart rate (90 beats per minute) and his cardiac status. Beta-blocker therapy should not be discontinued because doing so in the perioperative period is associated with an increased risk of adverse events such as cardiac death and MI.

Dr. Sweitzer: I would push up the metoprolol a bit to reduce the heart rate, knowing that beta-blockers are probably not the most efficacious antihypertensive agents. I would caution against starting an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) because he is scheduled to undergo a fairly significant procedure with expected blood loss and fluid shifts, and either of those agents in combination with a beta-blocker would be challenging to manage on the day of surgery.

Question 2.3: How would you manage his metformin perioperatively?

A. Discontinue it 48 hours preoperatively

B. Discontinue it 24 hours preoperatively

C. Withhold it on the morning of surgery

D. Continue it on the morning of surgery

Dr. Sweitzer: We routinely advise patients to hold all their oral diabetes medications the morning of surgery, primarily because many anesthesiologists are uncertain about the differing risks of hypoglycemia associated with the various oral agents.

Most of us will never see a patient who has lactic acidosis from metformin use. A systematic literature review and analysis found no increase in the risk of lactic acidosis with metformin compared with other oral hypoglycemics,⁶ so fear of lactic acidosis is not a valid reason to discontinue metformin. In fact, I think it is inappropriate to ever postpone or cancel surgery simply because the patient inadvertently took metformin on the morning of surgery. Some may argue that patients with renal insufficiency are at higher risk of lactic acidosis from metformin use on the morning of surgery, but keep in mind that renal insufficiency is a relative contra­indication to metformin use in the first place. Unless the patient is scheduled for a bilateral nephrectomy, his or her renal function is not going to be acutely reduced enough to enable a morning dose of metformin to cause lactic acidosis.

Dr. Cohn: Additionally, in a recent study of patients undergoing coronary artery bypass graft surgery (CABG), there was no increased risk of in-hospital morbidity or mortality in patients who received metformin on the morning of surgery,⁷ although I typically stop it 24 hours before major surgery.

Question 2.4: With respect to statin therapy, which course would you choose preoperatively?

A. Start a statin at a low dose

B. Start a statin at an intermediate dose

C. Start a statin at a high dose

D. Do not start a statin

Dr. Cohn: The answer to this question is not clear cut. The reason not to start a prophylactic statin would be the lack of evidence of benefit in patients undergoing noncardiac, nonvascular surgery, although there is evidence of potential benefit in patients undergoing vascular surgery.* The arguments in favor of starting a statin are that this patient has independent indications for a statin and the planned surgery is a high-risk procedure.

(* Editor’s note: In the time since this summit, results of the DECREASE-IV trial were published [Dunkelgrun et al, Ann Surg 2009; 249:921–926], showing a statisically nonsignificant trend toward improved outcomes at 30 days with fluvastatin in intermediate-risk patients undergoing noncardiovascular surgery.)

In cohort studies, perioperative death rates have been lower in statin recipients than in those not taking a statin.⁸ In the Dutch Echographic Cardiac Risk Evaluation Applying Stress Echo III (DECREASE III), which randomized noncardiac vascular surgery patients to perioperative fluvastatin or placebo, rates of MI and the composite end point of nonfatal MI or cardiovascular death were significantly lower in the statin group than in the placebo group.⁹

Question 2.5: Which of the following cardiac tests would you order preoperatively?

A. Exercise ECG

B. Dobutamine stress echocardiogram

C. Dipyridamole nuclear imaging

D. Coronary angiography

E. No further cardiac testing

Dr. Cohn: I wouldn’t do any cardiac testing since this patient needs surgery for his malignancy and the results of any testing would be highly unlikely to change management, in terms of canceling the surgery. This approach is consistent with the 2007 guidelines on perioperative cardiovascular evaluation for noncardiac surgery issued by the American College of Cardiology (ACC) and the American Heart Association (AHA).¹⁰

Dr. Sweitzer: I would differ on this question. This patient has not been evaluated adequately for his coronary artery disease. He has poor functional capacity that complicates assessment of his symptoms. He also has diabetes, so he is more likely to have silent myocardial ischemia. At age 78, he is understandably concerned about his survival: radical cystectomy is a major operation associated with significant blood loss, fluid shifts, and a long-term recuperative state. In this case, a cardiac evaluation may change management, not in terms of considering coronary revascularization before the surgery, but in terms of affecting the assessment of his chance of surviving this major operation, his life span following the operation, and his quality of life. For example, a highly positive dobutamine stress echo­cardiogram or certain wall motion abnormalities would suggest that he might not be protected even by optimal perioperative medical management.

Question 2.6: Which of the following would you do pre­operatively to assess pulmonary risk?

A. Obtain pulmonary function tests

B. Order a sleep study

C. Both

D. Neither

Dr. Sweitzer: There is no evidence supporting routine pulmonary function tests for patients undergoing procedures other than lung resection. If obstructive sleep apnea were suspected, I would order a sleep study only if I had access to one quickly to avoid delaying the surgery. Cancer surgery should never be delayed to get a sleep study. However, if this patient were seen in the primary care clinic, I would order a sleep study and, if indicated, put him on continuous positive airway pressure (CPAP). Whether or not preoperative CPAP makes a difference hasn’t been shown. No randomized controlled trials have been conducted, but there are some suggestions that the risks of ischemia and atrial arrhythmias in patients with known coronary artery disease can be reduced with CPAP. It is not always easy to initiate CPAP postoperatively because the number of CPAP machines is limited and titration by a respiratory technician is required, which is typically done in a sleep lab.

How the case was actually managed

Neither an HbA_1c measurement nor a lipid profile was ordered preoperatively, for lack of supportive evidence. The patient was continued on his beta-blocker and the dosage was increased sufficiently to control his blood pressure and heart rate. Metformin was continued, and statin therapy was begun preoperatively in light of the patient’s independent indications for it and the high-risk nature of the procedure. Stress testing was not ordered, in light of the lack of indication, given the patient’s stable angina. The patient refused a sleep study. The operation was lengthy and involved significant blood loss. The patient had a complicated postoperative course and ultimately died from multiorgan failure.

Scenario A: A 75-year-old man with diabetes, class III angina, and Q waves in inferior leads on his ECG is scheduled for elective femoropopliteal bypass surgery. His medications include isosorbide mononitrate (120 mg), amlodipine (10 mg), metoprolol controlled release (100 mg), atorvastatin (80 mg), insulin, and aspirin (81 mg). His heart rate is 64 beats per minute, blood pressure is controlled at 120/80 mm Hg, low-density lipoprotein cholesterol is 80 mg/dL, and creatinine is 1.5 μmol/L.

Scenario B: Consider the same patient undergoing elective cholecystectomy instead of a femoropopliteal bypass.

Scenario C: Consider the same patient scheduled for a cystoscopy instead of the other procedures. He had one episode of gross hematuria 1 week ago that resolved. Work-up by his urologist included a urinalysis and culture that were normal, cytology that was negative for malignancy, and a sonogram and computed tomography scan that were both negative. He has had no further bleeding and is not anemic. The urologist wants to do the cystoscopy for the sake of completeness.

Question 3.1: What would be your preoperative course of action in the above scenarios?

A. Order a dobutamine stress echocardiogram

B. Order nuclear imaging with dipyridamole or adenosine

C. Order coronary angiography

D. Order a resting two-dimensional echocardiogram

E. Continue his current medications and send to surgery with no further testing

Dr. Cohn: This is a man with an active cardiac condition and class III angina, which is considered severe angina in the ACC/AHA 2007 guidelines on peri­operative cardiac evaluation and care.¹⁰ The guidelines’ recommendation is to delay surgery for further evaluation and treatment. He is already on maximal medical therapy, which has failed to control his symptoms. He has poor exercise capacity. The only difference among the case scenarios is a variation in surgical risk.

This patient has independent indications for coronary angiography regardless of whether or not he’s undergoing surgery. He deserves evaluation for possible revascularization to improve his quality of life and symptoms.

I would send the patient to the catheterization lab in every one of these instances, with the possible exception of the cystoscopy scenario, where one could argue that revascularization with stenting would require antiplatelet therapy that might increase the bleeding risk, and also that the antiplatelet therapy would have to be interrupted for the cystoscopy, potentially increasing thrombotic risk.

Dr. Sweitzer: I disagree. The ACC/AHA 2007 guidelines do not recommend going directly to catheterization but rather recommend delaying surgery for further evaluation and treatment.¹⁰ We must ask whether this patient is truly receiving optimal medical management. After all, he is not on an ACE inhibitor or an ARB.

We must also consider whether the surgery is truly elective. In the first scenario, if he has peripheral vascular disease, he is likely to develop gangrene and have a further decrease in exercise capacity, which reduces his functional ability and increases his risk of comorbid conditions. He is at significant risk of developing worsening renal insufficiency or renal failure if he undergoes angiography. Coronary revascularization will delay treatment of his peripheral vascular disease. The Coronary Artery Revascularization Prophylaxis (CARP) trial showed no benefit of coronary revascularization relative to medical management in patients undergoing vascular surgery,¹¹ as is planned for this patient. I believe one must balance two competing risks and have an in-depth discussion with the patient.

In the second scenario, not treating gallstones or preventing cholelithiasis poses more risk to the health of this diabetic patient than does elective surgery if he needs a cholecystectomy. Emergency surgery, especially for acute cholecystitis, also significantly increases the risk of a cardiac event.

In the third scenario, the cystoscopy may uncover bladder cancer, which may be adversely affected by a delay of surgery. Regardless, the patient had gross hematuria and would be at risk for further bleeding should he undergo stenting with the requisite antiplatelet therapy.

Catheterization is not normally recommended unless CABG or stenting is being considered, yet I have seen no data that either of these procedures prolongs life except in very limited circumstances such as left main disease treated with bypass grafting. Though it is true that CABG reduces the incidence and severity of angina, it does not modify the physiologic cause of angina but rather may result in symptom improvement by damaging somatic nerve fibers to the heart. Putting a stent in this patient would be like applying a bandage: his symptoms will likely recur if he does not receive optimal medical management.

In a 2007 science advisory, several major medical societies cautioned against percutaneous coronary intervention (PCI) with drug-eluting stent placement in patients expected to undergo noncardiac surgery that would require interruption of antiplatelet therapy in the following 12 months (and against PCI with bare metal stent placement in patients undergoing such surgery in the following 4 to 6 weeks).¹² Therefore, I would not recommend catheterization for a patient whose noncardiac disease is likely to require surgery in the very near future, as is the case in each of the surgical scenarios above. One could consider noninvasive stress testing, which would be a safer approach and would almost certainly identify either significant stenosis of the left main coronary artery or three-vessel disease, which would be the only possible reasons to recommend CABG. I don’t believe there is any role for PCI for this patient.

Dr. Cohn: I argue for symptom relief even if it doesn’t prolong life. This patient cannot walk across the room without having symptoms despite taking multiple medications. I think he deserves a chance at revascularization if the angiogram shows he has a stenosis amenable to it, but I agree that a drug-eluting stent should not be placed if we know that he will undergo surgery within a few months.

A 60-year-old woman is scheduled for ventral hernia repair. Her medical history is unremarkable, with the exception of hypertension. She denies any bleeding problems and had no complications after a laparoscopic cholecystectomy 10 years ago. She has no family history of bleeding disorders.

Question 4.1: Would you order a prothrombin time (PT)/partial thromboplastin time (PTT)?

A. Yes