Anemia is a potent risk factor for mortality and morbidity in surgical patients, and its management has begun to shift away from allogeneic blood transfusion in recent years. This article reviews the clinical importance of perioperative anemia, the role and shortcomings of blood transfusion, and the pros and cons of alternative approaches to managing perioperative anemia. I conclude with an overview of a program for perioperative blood product use at my institution, Cleveland Clinic.

SIGNIFICANCE OF PERIOPERATIVE ANEMIA

Prevalence depends on many factors

The reported prevalence of anemia in surgical patients varies widely—from 5% to 76%¹—and depends on the patient’s disease and comorbidities, the surgical procedure and associated blood loss, and the definition of anemia used. The prevalence of preoperative anemia increases with patient age and is higher in women than in men.²

A multiplier of risk

Anemia is an important multiplier of mortality risk. For example, the presence of anemia raises the relative risk of 2-year mortality from 2.05 to 3.37 in patients with chronic kidney disease, from 2.86 to 3.78 in patients with heart failure, and from 4.86 to 6.07 in patients with concomitant heart failure and chronic kidney disease.³

Adverse effects of anemia have been demonstrated specifically in the perioperative setting as well. A large retrospective cohort study showed that a preoperative hemoglobin concentration of less than 6 g/dL increases the risk of death 30 days after surgery by a factor of 26 relative to a concentration of 12 g/dL or greater in surgical patients who declined blood transfusion for religious reasons.⁴ The anemia-associated mortality risk was especially pronounced among patients with cardiovascular disease.⁴ Other studies have demonstrated perioperative anemia to be associated with increases in the risk of death,⁵ cardiac events,⁶ pneumonia,⁷ and postoperative delirium.⁸

IS BLOOD TRANSFUSION THE ANSWER

The use of allogeneic blood transfusion to manage anemia and blood loss is a concept that originated several centuries ago and has changed little over the years.

Blood supply challenges

Blood collection has historically lagged demand, resulting in a blood supply insufficient to meet transfusion needs. According to the federal government’s 2007 National Blood Collection and Utilization Survey Report, 6.89% of US hospitals reported that they cancelled elective surgery on 1 or more days in the prior year because of a lack of blood availability, and 13.5% experienced at least 1 day in which nonsurgical blood needs could not be met.⁹ Unless practices are changed to increase blood donation, these unmet tranfusion needs may grow.

Joint Commission set to measure blood management

In response to this challenge, an advisory panel formed by the Joint Commission has identified 17 performance measures related to blood conservation and appropriate transfusion.¹⁰ These measures are currently in development, and we expect to see some types of metrics in the near future. Such metrics are likely to further prioritize blood management for US hospitals.

Safety of the blood supply: Viral transmission down, TRALI risk persists

The safety of the blood supply has improved markedly. Sophisticated testing and public demand have led to a dramatic decline in the risk of transfusion-related transmission of HIV, hepatitis C virus, and hepatitis B virus.¹¹

Despite this progress, the risk of transfusion-related acute lung injury (TRALI) has persisted in recent years. TRALI is characterized by acute onset of noncardiogenic pulmonary edema within 6 hours of blood product transfusion. Believed to be immune-mediated, TRALI is thought to occur as antibodies to human leukocyte antigens develop, inducing capillary leak syndrome.¹² The patients most commonly affected are those who receive plasma from multiparous female donors. A recent evaluation of transfusion-related fatalities reported to the US Food and Drug Administration (FDA) revealed a continual rise in fatal TRALI cases in the United States from 2001 to 2006.^13–15 TRALI was implicated in more than half of all transfusion-related fatalities reported to the FDA in 2006, a higher number than for any other single cause.¹³

At the same time, there is evidence that hemovigilance can reduce TRALI risk. In the United Kingdom, the Serious Hazards of Transfusion Steering Group introduced in late 2003 a policy of using plasma from male donors as much as possible, in view of the association of TRALI with plasma from multiparous female donors. The effort appeared to pay off: whereas TRALI accounted for 6.8% of all transfusion-related adverse events reported in the United Kingdom during the period 1996–2003,¹⁶ this proportion declined to just 1.9% in 2006.¹⁷

Finally, despite the progress in screening blood for more established infections like HIV and the hepatitis viruses, some additional infections now must be considered when assessing blood supply safety. These include diseases newly recognized as being transmissible by blood, or for which blood donor screening is not currently available, or that are newly emergent infections for which the potential for spread by transfusion is unknown. For such diseases—which include malaria and West Nile virus—the risk of transmission through transfusion is low, as they are much more likely to be acquired by other means.

Transfusion and outcomes: Not a strong record

Transfusion has never undergone safety and efficacy evaluation by the FDA. Given the challenges of conducting a randomized study of transfusion in the peri­operative setting, we may never have high-quality data to assess transfusion in this setting.

A few studies merit mention, however. The Transfusion Requirement in Critical Care (TRICC) trial was conducted in 838 critically ill patients in the intensive care setting.¹⁸ Patients were randomized to a strategy of either liberal transfusion (begun when hemoglobin fell below 10 g/dL) or restrictive transfusion (begun when hemoglobin fell below 7 g/dL). Thirty-day mortality was similar between patients in the two strategy groups, but the restrictive strategy was associated with significantly lower mortality in at least two subgroups: patients with myocardial infarction and patients with pulmonary edema. Further subgroup analysis found no benefit of early or aggressive transfusion in patients with coronary artery disease or in those requiring mechanical ventilation.

Rao et al performed a meta-analysis of three large international trials of patients with acute coronary syndromes to determine whether blood transfusion to correct anemia in this setting was associated with improved survival.¹⁹ They found significantly higher mortality among patients who underwent transfusion compared with those who did not, prompting them to urge caution in the use of transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease.

Similarly, a risk-adjusted, propensity-matched analysis of 6,301 patients undergoing noncardiac surgery found that receipt of 4 U of blood or more was a predictor of greater mortality, higher risk of infection, and longer hospital stay.²⁰ Moreover, in an observational cohort study of 11,963 patients who underwent isolated coronary artery bypass graft surgery, each unit of red blood cells transfused was associated with an incrementally increased risk of adverse outcome (eg, mortality, renal injury, need for ventilator support, lengthened hospital stay, infection).²¹ The latter study found that transfusion was the single factor most reliably associated with increased risk of postoperative morbidity.

Additional studies have echoed these findings—ie, that perioperative blood transfusion has been associated with a host of adverse outcomes, including increased morbidity and length of stay, increased rates of post­operative infection, as well as immunosuppression, viral transmission, and acute transfusion reactions.^5,22,23

An interesting factor in the relation between transfusion and outcomes is the shelf life of the blood being transfused. The FDA currently allows storage of blood for a maximum of 42 days, but a recent study of patients who received red blood cell transfusions during cardiac surgery found that those who received “older blood” (stored for > 14 days) had significantly higher rates of sepsis, prolonged intubation, renal failure, in-hospital mortality, and 1-year mortality compared with those who received “newer blood” (stored for ≤ 14 days).²⁴

These differing outcomes are generally attributed to the so-called storage defect: as blood gets older, it loses components such as 2,3-DPG and adenosine disphosphate, its red cells lose deformability, and it undergoes buildup of cytokines and free hemoglobin. Increased demand for newer blood in light of the storage defect could further intensify pressures on the blood supply.

MANAGEMENT OF PERIOPERATIVE ANEMIA

In light of these shortcomings of blood transfusion, how should anemia be managed perioperatively to reduce or avoid the need for transfusion?

Preoperative evaluation

Vigilance for anemia and related issues in the preoperative evaluation is fundamental. The evaluation should elicit a history of bleeding tendencies, previous transfusions, and symptoms of anemia. Medications should be reviewed with an eye toward any that may predispose to perioperative bleeding and anemia, such as aspirin, clopidogrel, and anticoagulants. During the physical examination, alertness for pallor and petechiae is key, as is attentiveness to symptoms of anemia such as shortness of breath and fatigue.

Overview of management options

Once the cause of anemia is identified, the choice for optimal medical management can be made. Choices broadly consist of pharmacologic and technological options. The former include iron supplements and erythropoiesis-stimulating agents. Among other pharmacologic options are thrombin, collagen, fibrin glue, tranexamic acid, and aminocaproic acid, but these agents are less well studied and will not be discussed here. Technological options include preoperative autologous blood donation, cell salvage, and acute normovolemic hemodilution.

In addition to these options, careful management of anticoagulant and antiplatelet medications should be provided, including discontinuation or substitution of drugs that could hamper clotting perioperatively.

PHARMACOLOGIC OPTIONS

Iron supplementation

Oral iron is available in four preparations: ferrous sulfate, ferrous gluconate, ferrous fumarate, and iron polysaccharide. Gastrointestinal side effects may limit these preparations’ tolerability. Iron supplements with a high elemental value will require fewer pills and fewer doses, reducing the risk or frequency of side effects.

Intravenous (IV) iron preparations are much safer now than they were years ago, when anaphylactic reactions were a concern. The ones generally used in the perioperative setting are iron sucrose and iron gluconate. Unlike the older IV preparations, the use of iron sucrose and iron gluconate often requires a second dose. The effect on hemoglobin levels usually occurs starting at 1 week, with the maximum effect achieved at 2 weeks. Hypotension, arthralgia, abdominal discomfort, and back pain are potential side effects of IV iron.

Efficacy and safety of iron supplementation. Evidence of the efficacy of preoperative iron supplementation is mounting. A study of 569 patients undergoing colorectal cancer surgery found that among the 116 patients who were anemic, intraoperative transfusion was needed in a significantly lower proportion of those who received 2 weeks of preoperative oral iron supplementation (200 mg) compared with those who received no iron therapy (9.4% vs 27.4%; P < .05).²⁶ Similarly, in an uncontrolled study, 10 days of IV iron sucrose starting 4 weeks preoperatively significantly increased hemoglobin levels in 20 patients with iron-deficiency anemia prior to elective orthopedic surgery.²⁷

Risks of infection and cancer progression have been concerns with IV iron therapy. However, no significant association between IV iron therapy and bacteremia was identified in a prospective study of 985 patients receiving chronic hemodialysis.²⁸ The effect of IV iron administration on tumor progression has not been prospectively studied.

In general, IV iron, especially the newer forms, is a safer alternative to blood transfusion. Death occurs at a much lower rate with iron than with blood transfusion (0.4 per million vs 4 per million, respectively), as do life-threatening adverse events (4 per million vs 10 per million, respectively), according to a systematic review by the Network for Advancement of Transfusion Alternatives.²⁹

Erythropoiesis-stimulating agents

Erythropoiesis-stimulating agents (ESAs) include epoetin alfa (erythropoietin), first approved by the FDA in 1989, and the more recently introduced darbe­poetin alfa. They are approved to treat anemia in several patient populations, but only epoetin alfa is approved by the FDA explicitly for use in patients undergoing major surgery (to reduce the need for blood transfusions). The ESAs have come under intense scrutiny in recent years over their risk-to-benefit ratio, as detailed below.

The preoperative dosing schedule for epoetin alfa is usually three weekly doses (plus a fourth dose on the day of surgery) if the surgery is scheduled 3 or more weeks in advance. However, daily dosing can be used effectively if the preoperative period is less than 3 weeks, provided that it is continued until 4 days after surgery. Oral iron is necessary throughout the course of epoetin alfa therapy.

Efficacy in reducing transfusions. In a systematic review published in 1998, epoetin alfa was shown to minimize perioperative exposure to allogeneic blood transfusion in patients undergoing orthopedic or cardiac surgery.³⁰ Its benefit was greatest in patients at the highest risk of requiring transfusion. It was effective whether given daily or weekly, and did not significantly increase the risk of thrombotic events when used in surgical patients, although some studies did find an excess of thrombotic events with its use.

In three randomized trials conducted in patients undergoing joint arthroplasty (hip or knee), epoetin alfa was associated with substantial and significant reductions in perioperative blood transfusion compared with placebo or preoperative autologous blood donation.^31–33 Rates of deep vein thrombosis (DVT) did not differ significantly between the epoetin alfa and placebo groups.

Concerns over perioperative thromboembolic risk. In early 2007, the FDA was made aware of preliminary results of an open-label study in which 681 patients undergoing elective spinal surgery who did not receive prophylactic anticoagulation were randomized to epoetin alfa plus standard-of-care therapy (pneumatic compression) or standard-of-care therapy alone.^34,35 The incidence of DVT was 4.7% in patients treated with epoetin alfa compared with 2.1% in those not receiving epoetin alfa. It is important to note that the available ESAs are prothrombotic and increase thrombotic risk significantly, especially in populations like this one in which pharmacologic DVT prophylaxis is not routinely used.

Based in part on this study, the FDA in 2007 required a boxed warning to be added to the ESAs’ package inserts to specify the increased risk of DVT with their use in surgical patients not receiving prophylactic anticoagulation. The warning urges consideration of the use of DVT prophylaxis in surgical patients receiving an ESA.^34,35

Autologous blood donation: A practice in decline

In cases of elective surgery, autologous blood donation can be used to protect against disease transmission and overcome the challenge of blood type compatibility. Preoperative autologous donation of blood has been a prevalent practice, but its use is declining. One reason is that waste is high (approximately 50% at Cleveland Clinic), which makes this practice more costly than is often realized. Also, autologous blood donation increases the likelihood that the patient will be anemic on the day of surgery, so that he or she may still need allogeneic blood after all, defeating the initial purpose. Despite these limitations, preoperative autologous blood donation remains a useful option for a subset of patients with multiple antibodies for whom donor blood may be difficult to obtain.

Cell salvage

Cell salvage is an innovative technology that recovers the patient’s own blood (after being shed from the surgical incision) for transfusion after filtering and washing. It is particularly well suited to procedures that involve massive blood loss. Cell savage requires technical expertise, however, and involves costs associated with both the machine and disposables.

Restricted postoperative phlebotomy

Phlebotomy accounts for a significant amount of blood loss, especially in intensive care patients with arterial lines. The equivalent of 30% of total blood transfused has been reported to be lost to phlebotomy during an intensive care unit stay.³⁶ Triggers for transfusion cannot be assigned universally based on blood loss from phlebotomy but must consider the patient’s hemodynamic status, cardiac reserve, and other clinical characteristics.

PROMOTING RESPONSIBLE BLOOD PRODUCT USE

Blood is expensive, and in recent years hospitals have experienced increases in the cost of blood and blood products. To promote responsible blood use, we have developed a multipronged approach to blood management at Cleveland Clinic. The program’s cornerstone is increased awareness of the risks associated with blood transfusions. The emphasis is on educating staff physicians and other caregivers about the appropriate use of blood products. We also have implemented a new policy requiring staff authorization for all blood requested in nonemergency situations. Additionally, requests for blood components require adherence to an indication-based ordering process. Finally, data about blood use are shared transparently among physicians, encouraging good clinical practice.

In the first 7 months of the program, we observed decreased utilization of blood products in the inpatient setting. Notably, the reduction in blood use was significantly greater in the surgical population than in the medical population.

CONCULSIONS

Anemia is associated with increased morbidity and mortality in the perioperative setting. Perioperative blood transfusion is one method of raising hemoglobin levels in anemic surgical patients, but it increases perioperative morbidity in the form of acute transfusion reactions, immunosuppression, postoperative infection, and longer hospital stays. Moreover, blood collection continues to lag blood demand. For these reasons, most relevant major medical organizations—including the Association of Blood Banks, the American Red Cross, and the FDA—advise that red blood cell–containing components should not be used to treat anemias that can be corrected with medications. These medical alternatives—all of which can be used in the perioperative setting—include iron supplementation, vitamin B₁₂, and ESAs in select patient groups.

DISCUSSION

Question from the audience: Are there risks involved with autologous blood donation? Are different hemoglobin thresholds used when a patient’s own blood is used?

Dr. Kumar: As I mentioned, preoperative autologous donation is a technique that is less frequently used in our hospital. Autologous transfusion is considered safe only for patients who come to the clinic with normal hemoglobin values. Some patients may not have recovered from their blood loss by the time they come to surgery, so you end up needing to give them more blood because they started out anemic.

Question from the audience: Is there risk to giving patients back their own blood? Do you have to worry about transfusion-induced lung injury, sepsis, or other complications?

Dr. Kumar: As with allogeneic blood, the risk of clerical or clinical error exists with autologous blood: it too needs to be kept on the shelf, taken out, and infused, and the risk of sepsis remains the same.

Anemia is a potent risk factor for mortality and morbidity in surgical patients, and its management has begun to shift away from allogeneic blood transfusion in recent years. This article reviews the clinical importance of perioperative anemia, the role and shortcomings of blood transfusion, and the pros and cons of alternative approaches to managing perioperative anemia. I conclude with an overview of a program for perioperative blood product use at my institution, Cleveland Clinic.

SIGNIFICANCE OF PERIOPERATIVE ANEMIA

Prevalence depends on many factors

The reported prevalence of anemia in surgical patients varies widely—from 5% to 76%¹—and depends on the patient’s disease and comorbidities, the surgical procedure and associated blood loss, and the definition of anemia used. The prevalence of preoperative anemia increases with patient age and is higher in women than in men.²

A multiplier of risk

Anemia is an important multiplier of mortality risk. For example, the presence of anemia raises the relative risk of 2-year mortality from 2.05 to 3.37 in patients with chronic kidney disease, from 2.86 to 3.78 in patients with heart failure, and from 4.86 to 6.07 in patients with concomitant heart failure and chronic kidney disease.³

Adverse effects of anemia have been demonstrated specifically in the perioperative setting as well. A large retrospective cohort study showed that a preoperative hemoglobin concentration of less than 6 g/dL increases the risk of death 30 days after surgery by a factor of 26 relative to a concentration of 12 g/dL or greater in surgical patients who declined blood transfusion for religious reasons.⁴ The anemia-associated mortality risk was especially pronounced among patients with cardiovascular disease.⁴ Other studies have demonstrated perioperative anemia to be associated with increases in the risk of death,⁵ cardiac events,⁶ pneumonia,⁷ and postoperative delirium.⁸

IS BLOOD TRANSFUSION THE ANSWER

The use of allogeneic blood transfusion to manage anemia and blood loss is a concept that originated several centuries ago and has changed little over the years.

Blood supply challenges

Blood collection has historically lagged demand, resulting in a blood supply insufficient to meet transfusion needs. According to the federal government’s 2007 National Blood Collection and Utilization Survey Report, 6.89% of US hospitals reported that they cancelled elective surgery on 1 or more days in the prior year because of a lack of blood availability, and 13.5% experienced at least 1 day in which nonsurgical blood needs could not be met.⁹ Unless practices are changed to increase blood donation, these unmet tranfusion needs may grow.

Joint Commission set to measure blood management

In response to this challenge, an advisory panel formed by the Joint Commission has identified 17 performance measures related to blood conservation and appropriate transfusion.¹⁰ These measures are currently in development, and we expect to see some types of metrics in the near future. Such metrics are likely to further prioritize blood management for US hospitals.

Safety of the blood supply: Viral transmission down, TRALI risk persists

The safety of the blood supply has improved markedly. Sophisticated testing and public demand have led to a dramatic decline in the risk of transfusion-related transmission of HIV, hepatitis C virus, and hepatitis B virus.¹¹

Despite this progress, the risk of transfusion-related acute lung injury (TRALI) has persisted in recent years. TRALI is characterized by acute onset of noncardiogenic pulmonary edema within 6 hours of blood product transfusion. Believed to be immune-mediated, TRALI is thought to occur as antibodies to human leukocyte antigens develop, inducing capillary leak syndrome.¹² The patients most commonly affected are those who receive plasma from multiparous female donors. A recent evaluation of transfusion-related fatalities reported to the US Food and Drug Administration (FDA) revealed a continual rise in fatal TRALI cases in the United States from 2001 to 2006.^13–15 TRALI was implicated in more than half of all transfusion-related fatalities reported to the FDA in 2006, a higher number than for any other single cause.¹³

At the same time, there is evidence that hemovigilance can reduce TRALI risk. In the United Kingdom, the Serious Hazards of Transfusion Steering Group introduced in late 2003 a policy of using plasma from male donors as much as possible, in view of the association of TRALI with plasma from multiparous female donors. The effort appeared to pay off: whereas TRALI accounted for 6.8% of all transfusion-related adverse events reported in the United Kingdom during the period 1996–2003,¹⁶ this proportion declined to just 1.9% in 2006.¹⁷

Finally, despite the progress in screening blood for more established infections like HIV and the hepatitis viruses, some additional infections now must be considered when assessing blood supply safety. These include diseases newly recognized as being transmissible by blood, or for which blood donor screening is not currently available, or that are newly emergent infections for which the potential for spread by transfusion is unknown. For such diseases—which include malaria and West Nile virus—the risk of transmission through transfusion is low, as they are much more likely to be acquired by other means.

Transfusion and outcomes: Not a strong record

Transfusion has never undergone safety and efficacy evaluation by the FDA. Given the challenges of conducting a randomized study of transfusion in the peri­operative setting, we may never have high-quality data to assess transfusion in this setting.

A few studies merit mention, however. The Transfusion Requirement in Critical Care (TRICC) trial was conducted in 838 critically ill patients in the intensive care setting.¹⁸ Patients were randomized to a strategy of either liberal transfusion (begun when hemoglobin fell below 10 g/dL) or restrictive transfusion (begun when hemoglobin fell below 7 g/dL). Thirty-day mortality was similar between patients in the two strategy groups, but the restrictive strategy was associated with significantly lower mortality in at least two subgroups: patients with myocardial infarction and patients with pulmonary edema. Further subgroup analysis found no benefit of early or aggressive transfusion in patients with coronary artery disease or in those requiring mechanical ventilation.

Rao et al performed a meta-analysis of three large international trials of patients with acute coronary syndromes to determine whether blood transfusion to correct anemia in this setting was associated with improved survival.¹⁹ They found significantly higher mortality among patients who underwent transfusion compared with those who did not, prompting them to urge caution in the use of transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease.

Similarly, a risk-adjusted, propensity-matched analysis of 6,301 patients undergoing noncardiac surgery found that receipt of 4 U of blood or more was a predictor of greater mortality, higher risk of infection, and longer hospital stay.²⁰ Moreover, in an observational cohort study of 11,963 patients who underwent isolated coronary artery bypass graft surgery, each unit of red blood cells transfused was associated with an incrementally increased risk of adverse outcome (eg, mortality, renal injury, need for ventilator support, lengthened hospital stay, infection).²¹ The latter study found that transfusion was the single factor most reliably associated with increased risk of postoperative morbidity.

Additional studies have echoed these findings—ie, that perioperative blood transfusion has been associated with a host of adverse outcomes, including increased morbidity and length of stay, increased rates of post­operative infection, as well as immunosuppression, viral transmission, and acute transfusion reactions.^5,22,23

An interesting factor in the relation between transfusion and outcomes is the shelf life of the blood being transfused. The FDA currently allows storage of blood for a maximum of 42 days, but a recent study of patients who received red blood cell transfusions during cardiac surgery found that those who received “older blood” (stored for > 14 days) had significantly higher rates of sepsis, prolonged intubation, renal failure, in-hospital mortality, and 1-year mortality compared with those who received “newer blood” (stored for ≤ 14 days).²⁴

These differing outcomes are generally attributed to the so-called storage defect: as blood gets older, it loses components such as 2,3-DPG and adenosine disphosphate, its red cells lose deformability, and it undergoes buildup of cytokines and free hemoglobin. Increased demand for newer blood in light of the storage defect could further intensify pressures on the blood supply.

MANAGEMENT OF PERIOPERATIVE ANEMIA

In light of these shortcomings of blood transfusion, how should anemia be managed perioperatively to reduce or avoid the need for transfusion?

Preoperative evaluation

Vigilance for anemia and related issues in the preoperative evaluation is fundamental. The evaluation should elicit a history of bleeding tendencies, previous transfusions, and symptoms of anemia. Medications should be reviewed with an eye toward any that may predispose to perioperative bleeding and anemia, such as aspirin, clopidogrel, and anticoagulants. During the physical examination, alertness for pallor and petechiae is key, as is attentiveness to symptoms of anemia such as shortness of breath and fatigue.

Overview of management options

Once the cause of anemia is identified, the choice for optimal medical management can be made. Choices broadly consist of pharmacologic and technological options. The former include iron supplements and erythropoiesis-stimulating agents. Among other pharmacologic options are thrombin, collagen, fibrin glue, tranexamic acid, and aminocaproic acid, but these agents are less well studied and will not be discussed here. Technological options include preoperative autologous blood donation, cell salvage, and acute normovolemic hemodilution.

In addition to these options, careful management of anticoagulant and antiplatelet medications should be provided, including discontinuation or substitution of drugs that could hamper clotting perioperatively.

PHARMACOLOGIC OPTIONS

Iron supplementation

Oral iron is available in four preparations: ferrous sulfate, ferrous gluconate, ferrous fumarate, and iron polysaccharide. Gastrointestinal side effects may limit these preparations’ tolerability. Iron supplements with a high elemental value will require fewer pills and fewer doses, reducing the risk or frequency of side effects.

Intravenous (IV) iron preparations are much safer now than they were years ago, when anaphylactic reactions were a concern. The ones generally used in the perioperative setting are iron sucrose and iron gluconate. Unlike the older IV preparations, the use of iron sucrose and iron gluconate often requires a second dose. The effect on hemoglobin levels usually occurs starting at 1 week, with the maximum effect achieved at 2 weeks. Hypotension, arthralgia, abdominal discomfort, and back pain are potential side effects of IV iron.

Efficacy and safety of iron supplementation. Evidence of the efficacy of preoperative iron supplementation is mounting. A study of 569 patients undergoing colorectal cancer surgery found that among the 116 patients who were anemic, intraoperative transfusion was needed in a significantly lower proportion of those who received 2 weeks of preoperative oral iron supplementation (200 mg) compared with those who received no iron therapy (9.4% vs 27.4%; P < .05).²⁶ Similarly, in an uncontrolled study, 10 days of IV iron sucrose starting 4 weeks preoperatively significantly increased hemoglobin levels in 20 patients with iron-deficiency anemia prior to elective orthopedic surgery.²⁷

Risks of infection and cancer progression have been concerns with IV iron therapy. However, no significant association between IV iron therapy and bacteremia was identified in a prospective study of 985 patients receiving chronic hemodialysis.²⁸ The effect of IV iron administration on tumor progression has not been prospectively studied.

In general, IV iron, especially the newer forms, is a safer alternative to blood transfusion. Death occurs at a much lower rate with iron than with blood transfusion (0.4 per million vs 4 per million, respectively), as do life-threatening adverse events (4 per million vs 10 per million, respectively), according to a systematic review by the Network for Advancement of Transfusion Alternatives.²⁹

Erythropoiesis-stimulating agents

Erythropoiesis-stimulating agents (ESAs) include epoetin alfa (erythropoietin), first approved by the FDA in 1989, and the more recently introduced darbe­poetin alfa. They are approved to treat anemia in several patient populations, but only epoetin alfa is approved by the FDA explicitly for use in patients undergoing major surgery (to reduce the need for blood transfusions). The ESAs have come under intense scrutiny in recent years over their risk-to-benefit ratio, as detailed below.

The preoperative dosing schedule for epoetin alfa is usually three weekly doses (plus a fourth dose on the day of surgery) if the surgery is scheduled 3 or more weeks in advance. However, daily dosing can be used effectively if the preoperative period is less than 3 weeks, provided that it is continued until 4 days after surgery. Oral iron is necessary throughout the course of epoetin alfa therapy.

Efficacy in reducing transfusions. In a systematic review published in 1998, epoetin alfa was shown to minimize perioperative exposure to allogeneic blood transfusion in patients undergoing orthopedic or cardiac surgery.³⁰ Its benefit was greatest in patients at the highest risk of requiring transfusion. It was effective whether given daily or weekly, and did not significantly increase the risk of thrombotic events when used in surgical patients, although some studies did find an excess of thrombotic events with its use.

In three randomized trials conducted in patients undergoing joint arthroplasty (hip or knee), epoetin alfa was associated with substantial and significant reductions in perioperative blood transfusion compared with placebo or preoperative autologous blood donation.^31–33 Rates of deep vein thrombosis (DVT) did not differ significantly between the epoetin alfa and placebo groups.

Concerns over perioperative thromboembolic risk. In early 2007, the FDA was made aware of preliminary results of an open-label study in which 681 patients undergoing elective spinal surgery who did not receive prophylactic anticoagulation were randomized to epoetin alfa plus standard-of-care therapy (pneumatic compression) or standard-of-care therapy alone.^34,35 The incidence of DVT was 4.7% in patients treated with epoetin alfa compared with 2.1% in those not receiving epoetin alfa. It is important to note that the available ESAs are prothrombotic and increase thrombotic risk significantly, especially in populations like this one in which pharmacologic DVT prophylaxis is not routinely used.

Based in part on this study, the FDA in 2007 required a boxed warning to be added to the ESAs’ package inserts to specify the increased risk of DVT with their use in surgical patients not receiving prophylactic anticoagulation. The warning urges consideration of the use of DVT prophylaxis in surgical patients receiving an ESA.^34,35

Autologous blood donation: A practice in decline

In cases of elective surgery, autologous blood donation can be used to protect against disease transmission and overcome the challenge of blood type compatibility. Preoperative autologous donation of blood has been a prevalent practice, but its use is declining. One reason is that waste is high (approximately 50% at Cleveland Clinic), which makes this practice more costly than is often realized. Also, autologous blood donation increases the likelihood that the patient will be anemic on the day of surgery, so that he or she may still need allogeneic blood after all, defeating the initial purpose. Despite these limitations, preoperative autologous blood donation remains a useful option for a subset of patients with multiple antibodies for whom donor blood may be difficult to obtain.

Cell salvage

Cell salvage is an innovative technology that recovers the patient’s own blood (after being shed from the surgical incision) for transfusion after filtering and washing. It is particularly well suited to procedures that involve massive blood loss. Cell savage requires technical expertise, however, and involves costs associated with both the machine and disposables.

Restricted postoperative phlebotomy

Phlebotomy accounts for a significant amount of blood loss, especially in intensive care patients with arterial lines. The equivalent of 30% of total blood transfused has been reported to be lost to phlebotomy during an intensive care unit stay.³⁶ Triggers for transfusion cannot be assigned universally based on blood loss from phlebotomy but must consider the patient’s hemodynamic status, cardiac reserve, and other clinical characteristics.

PROMOTING RESPONSIBLE BLOOD PRODUCT USE

Blood is expensive, and in recent years hospitals have experienced increases in the cost of blood and blood products. To promote responsible blood use, we have developed a multipronged approach to blood management at Cleveland Clinic. The program’s cornerstone is increased awareness of the risks associated with blood transfusions. The emphasis is on educating staff physicians and other caregivers about the appropriate use of blood products. We also have implemented a new policy requiring staff authorization for all blood requested in nonemergency situations. Additionally, requests for blood components require adherence to an indication-based ordering process. Finally, data about blood use are shared transparently among physicians, encouraging good clinical practice.

In the first 7 months of the program, we observed decreased utilization of blood products in the inpatient setting. Notably, the reduction in blood use was significantly greater in the surgical population than in the medical population.

CONCULSIONS

Anemia is associated with increased morbidity and mortality in the perioperative setting. Perioperative blood transfusion is one method of raising hemoglobin levels in anemic surgical patients, but it increases perioperative morbidity in the form of acute transfusion reactions, immunosuppression, postoperative infection, and longer hospital stays. Moreover, blood collection continues to lag blood demand. For these reasons, most relevant major medical organizations—including the Association of Blood Banks, the American Red Cross, and the FDA—advise that red blood cell–containing components should not be used to treat anemias that can be corrected with medications. These medical alternatives—all of which can be used in the perioperative setting—include iron supplementation, vitamin B₁₂, and ESAs in select patient groups.

DISCUSSION

Question from the audience: Are there risks involved with autologous blood donation? Are different hemoglobin thresholds used when a patient’s own blood is used?

Dr. Kumar: As I mentioned, preoperative autologous donation is a technique that is less frequently used in our hospital. Autologous transfusion is considered safe only for patients who come to the clinic with normal hemoglobin values. Some patients may not have recovered from their blood loss by the time they come to surgery, so you end up needing to give them more blood because they started out anemic.

Question from the audience: Is there risk to giving patients back their own blood? Do you have to worry about transfusion-induced lung injury, sepsis, or other complications?

Dr. Kumar: As with allogeneic blood, the risk of clerical or clinical error exists with autologous blood: it too needs to be kept on the shelf, taken out, and infused, and the risk of sepsis remains the same.

Anemia is a potent risk factor for mortality and morbidity in surgical patients, and its management has begun to shift away from allogeneic blood transfusion in recent years. This article reviews the clinical importance of perioperative anemia, the role and shortcomings of blood transfusion, and the pros and cons of alternative approaches to managing perioperative anemia. I conclude with an overview of a program for perioperative blood product use at my institution, Cleveland Clinic.

SIGNIFICANCE OF PERIOPERATIVE ANEMIA

Prevalence depends on many factors

The reported prevalence of anemia in surgical patients varies widely—from 5% to 76%¹—and depends on the patient’s disease and comorbidities, the surgical procedure and associated blood loss, and the definition of anemia used. The prevalence of preoperative anemia increases with patient age and is higher in women than in men.²

A multiplier of risk

Anemia is an important multiplier of mortality risk. For example, the presence of anemia raises the relative risk of 2-year mortality from 2.05 to 3.37 in patients with chronic kidney disease, from 2.86 to 3.78 in patients with heart failure, and from 4.86 to 6.07 in patients with concomitant heart failure and chronic kidney disease.³

Adverse effects of anemia have been demonstrated specifically in the perioperative setting as well. A large retrospective cohort study showed that a preoperative hemoglobin concentration of less than 6 g/dL increases the risk of death 30 days after surgery by a factor of 26 relative to a concentration of 12 g/dL or greater in surgical patients who declined blood transfusion for religious reasons.⁴ The anemia-associated mortality risk was especially pronounced among patients with cardiovascular disease.⁴ Other studies have demonstrated perioperative anemia to be associated with increases in the risk of death,⁵ cardiac events,⁶ pneumonia,⁷ and postoperative delirium.⁸

IS BLOOD TRANSFUSION THE ANSWER

The use of allogeneic blood transfusion to manage anemia and blood loss is a concept that originated several centuries ago and has changed little over the years.

Blood supply challenges

Blood collection has historically lagged demand, resulting in a blood supply insufficient to meet transfusion needs. According to the federal government’s 2007 National Blood Collection and Utilization Survey Report, 6.89% of US hospitals reported that they cancelled elective surgery on 1 or more days in the prior year because of a lack of blood availability, and 13.5% experienced at least 1 day in which nonsurgical blood needs could not be met.⁹ Unless practices are changed to increase blood donation, these unmet tranfusion needs may grow.

Joint Commission set to measure blood management

In response to this challenge, an advisory panel formed by the Joint Commission has identified 17 performance measures related to blood conservation and appropriate transfusion.¹⁰ These measures are currently in development, and we expect to see some types of metrics in the near future. Such metrics are likely to further prioritize blood management for US hospitals.

Safety of the blood supply: Viral transmission down, TRALI risk persists

The safety of the blood supply has improved markedly. Sophisticated testing and public demand have led to a dramatic decline in the risk of transfusion-related transmission of HIV, hepatitis C virus, and hepatitis B virus.¹¹

Despite this progress, the risk of transfusion-related acute lung injury (TRALI) has persisted in recent years. TRALI is characterized by acute onset of noncardiogenic pulmonary edema within 6 hours of blood product transfusion. Believed to be immune-mediated, TRALI is thought to occur as antibodies to human leukocyte antigens develop, inducing capillary leak syndrome.¹² The patients most commonly affected are those who receive plasma from multiparous female donors. A recent evaluation of transfusion-related fatalities reported to the US Food and Drug Administration (FDA) revealed a continual rise in fatal TRALI cases in the United States from 2001 to 2006.^13–15 TRALI was implicated in more than half of all transfusion-related fatalities reported to the FDA in 2006, a higher number than for any other single cause.¹³

At the same time, there is evidence that hemovigilance can reduce TRALI risk. In the United Kingdom, the Serious Hazards of Transfusion Steering Group introduced in late 2003 a policy of using plasma from male donors as much as possible, in view of the association of TRALI with plasma from multiparous female donors. The effort appeared to pay off: whereas TRALI accounted for 6.8% of all transfusion-related adverse events reported in the United Kingdom during the period 1996–2003,¹⁶ this proportion declined to just 1.9% in 2006.¹⁷

Finally, despite the progress in screening blood for more established infections like HIV and the hepatitis viruses, some additional infections now must be considered when assessing blood supply safety. These include diseases newly recognized as being transmissible by blood, or for which blood donor screening is not currently available, or that are newly emergent infections for which the potential for spread by transfusion is unknown. For such diseases—which include malaria and West Nile virus—the risk of transmission through transfusion is low, as they are much more likely to be acquired by other means.

Transfusion and outcomes: Not a strong record

Transfusion has never undergone safety and efficacy evaluation by the FDA. Given the challenges of conducting a randomized study of transfusion in the peri­operative setting, we may never have high-quality data to assess transfusion in this setting.

A few studies merit mention, however. The Transfusion Requirement in Critical Care (TRICC) trial was conducted in 838 critically ill patients in the intensive care setting.¹⁸ Patients were randomized to a strategy of either liberal transfusion (begun when hemoglobin fell below 10 g/dL) or restrictive transfusion (begun when hemoglobin fell below 7 g/dL). Thirty-day mortality was similar between patients in the two strategy groups, but the restrictive strategy was associated with significantly lower mortality in at least two subgroups: patients with myocardial infarction and patients with pulmonary edema. Further subgroup analysis found no benefit of early or aggressive transfusion in patients with coronary artery disease or in those requiring mechanical ventilation.

Rao et al performed a meta-analysis of three large international trials of patients with acute coronary syndromes to determine whether blood transfusion to correct anemia in this setting was associated with improved survival.¹⁹ They found significantly higher mortality among patients who underwent transfusion compared with those who did not, prompting them to urge caution in the use of transfusion to maintain arbitrary hematocrit levels in stable patients with ischemic heart disease.

Similarly, a risk-adjusted, propensity-matched analysis of 6,301 patients undergoing noncardiac surgery found that receipt of 4 U of blood or more was a predictor of greater mortality, higher risk of infection, and longer hospital stay.²⁰ Moreover, in an observational cohort study of 11,963 patients who underwent isolated coronary artery bypass graft surgery, each unit of red blood cells transfused was associated with an incrementally increased risk of adverse outcome (eg, mortality, renal injury, need for ventilator support, lengthened hospital stay, infection).²¹ The latter study found that transfusion was the single factor most reliably associated with increased risk of postoperative morbidity.

Additional studies have echoed these findings—ie, that perioperative blood transfusion has been associated with a host of adverse outcomes, including increased morbidity and length of stay, increased rates of post­operative infection, as well as immunosuppression, viral transmission, and acute transfusion reactions.^5,22,23

An interesting factor in the relation between transfusion and outcomes is the shelf life of the blood being transfused. The FDA currently allows storage of blood for a maximum of 42 days, but a recent study of patients who received red blood cell transfusions during cardiac surgery found that those who received “older blood” (stored for > 14 days) had significantly higher rates of sepsis, prolonged intubation, renal failure, in-hospital mortality, and 1-year mortality compared with those who received “newer blood” (stored for ≤ 14 days).²⁴

These differing outcomes are generally attributed to the so-called storage defect: as blood gets older, it loses components such as 2,3-DPG and adenosine disphosphate, its red cells lose deformability, and it undergoes buildup of cytokines and free hemoglobin. Increased demand for newer blood in light of the storage defect could further intensify pressures on the blood supply.

MANAGEMENT OF PERIOPERATIVE ANEMIA

In light of these shortcomings of blood transfusion, how should anemia be managed perioperatively to reduce or avoid the need for transfusion?

Preoperative evaluation

Vigilance for anemia and related issues in the preoperative evaluation is fundamental. The evaluation should elicit a history of bleeding tendencies, previous transfusions, and symptoms of anemia. Medications should be reviewed with an eye toward any that may predispose to perioperative bleeding and anemia, such as aspirin, clopidogrel, and anticoagulants. During the physical examination, alertness for pallor and petechiae is key, as is attentiveness to symptoms of anemia such as shortness of breath and fatigue.

Overview of management options

Once the cause of anemia is identified, the choice for optimal medical management can be made. Choices broadly consist of pharmacologic and technological options. The former include iron supplements and erythropoiesis-stimulating agents. Among other pharmacologic options are thrombin, collagen, fibrin glue, tranexamic acid, and aminocaproic acid, but these agents are less well studied and will not be discussed here. Technological options include preoperative autologous blood donation, cell salvage, and acute normovolemic hemodilution.

In addition to these options, careful management of anticoagulant and antiplatelet medications should be provided, including discontinuation or substitution of drugs that could hamper clotting perioperatively.

PHARMACOLOGIC OPTIONS

Iron supplementation

Oral iron is available in four preparations: ferrous sulfate, ferrous gluconate, ferrous fumarate, and iron polysaccharide. Gastrointestinal side effects may limit these preparations’ tolerability. Iron supplements with a high elemental value will require fewer pills and fewer doses, reducing the risk or frequency of side effects.

Intravenous (IV) iron preparations are much safer now than they were years ago, when anaphylactic reactions were a concern. The ones generally used in the perioperative setting are iron sucrose and iron gluconate. Unlike the older IV preparations, the use of iron sucrose and iron gluconate often requires a second dose. The effect on hemoglobin levels usually occurs starting at 1 week, with the maximum effect achieved at 2 weeks. Hypotension, arthralgia, abdominal discomfort, and back pain are potential side effects of IV iron.

Efficacy and safety of iron supplementation. Evidence of the efficacy of preoperative iron supplementation is mounting. A study of 569 patients undergoing colorectal cancer surgery found that among the 116 patients who were anemic, intraoperative transfusion was needed in a significantly lower proportion of those who received 2 weeks of preoperative oral iron supplementation (200 mg) compared with those who received no iron therapy (9.4% vs 27.4%; P < .05).²⁶ Similarly, in an uncontrolled study, 10 days of IV iron sucrose starting 4 weeks preoperatively significantly increased hemoglobin levels in 20 patients with iron-deficiency anemia prior to elective orthopedic surgery.²⁷

Risks of infection and cancer progression have been concerns with IV iron therapy. However, no significant association between IV iron therapy and bacteremia was identified in a prospective study of 985 patients receiving chronic hemodialysis.²⁸ The effect of IV iron administration on tumor progression has not been prospectively studied.

In general, IV iron, especially the newer forms, is a safer alternative to blood transfusion. Death occurs at a much lower rate with iron than with blood transfusion (0.4 per million vs 4 per million, respectively), as do life-threatening adverse events (4 per million vs 10 per million, respectively), according to a systematic review by the Network for Advancement of Transfusion Alternatives.²⁹

Erythropoiesis-stimulating agents

Erythropoiesis-stimulating agents (ESAs) include epoetin alfa (erythropoietin), first approved by the FDA in 1989, and the more recently introduced darbe­poetin alfa. They are approved to treat anemia in several patient populations, but only epoetin alfa is approved by the FDA explicitly for use in patients undergoing major surgery (to reduce the need for blood transfusions). The ESAs have come under intense scrutiny in recent years over their risk-to-benefit ratio, as detailed below.

The preoperative dosing schedule for epoetin alfa is usually three weekly doses (plus a fourth dose on the day of surgery) if the surgery is scheduled 3 or more weeks in advance. However, daily dosing can be used effectively if the preoperative period is less than 3 weeks, provided that it is continued until 4 days after surgery. Oral iron is necessary throughout the course of epoetin alfa therapy.

Efficacy in reducing transfusions. In a systematic review published in 1998, epoetin alfa was shown to minimize perioperative exposure to allogeneic blood transfusion in patients undergoing orthopedic or cardiac surgery.³⁰ Its benefit was greatest in patients at the highest risk of requiring transfusion. It was effective whether given daily or weekly, and did not significantly increase the risk of thrombotic events when used in surgical patients, although some studies did find an excess of thrombotic events with its use.

In three randomized trials conducted in patients undergoing joint arthroplasty (hip or knee), epoetin alfa was associated with substantial and significant reductions in perioperative blood transfusion compared with placebo or preoperative autologous blood donation.^31–33 Rates of deep vein thrombosis (DVT) did not differ significantly between the epoetin alfa and placebo groups.

Concerns over perioperative thromboembolic risk. In early 2007, the FDA was made aware of preliminary results of an open-label study in which 681 patients undergoing elective spinal surgery who did not receive prophylactic anticoagulation were randomized to epoetin alfa plus standard-of-care therapy (pneumatic compression) or standard-of-care therapy alone.^34,35 The incidence of DVT was 4.7% in patients treated with epoetin alfa compared with 2.1% in those not receiving epoetin alfa. It is important to note that the available ESAs are prothrombotic and increase thrombotic risk significantly, especially in populations like this one in which pharmacologic DVT prophylaxis is not routinely used.

Based in part on this study, the FDA in 2007 required a boxed warning to be added to the ESAs’ package inserts to specify the increased risk of DVT with their use in surgical patients not receiving prophylactic anticoagulation. The warning urges consideration of the use of DVT prophylaxis in surgical patients receiving an ESA.^34,35

Autologous blood donation: A practice in decline

In cases of elective surgery, autologous blood donation can be used to protect against disease transmission and overcome the challenge of blood type compatibility. Preoperative autologous donation of blood has been a prevalent practice, but its use is declining. One reason is that waste is high (approximately 50% at Cleveland Clinic), which makes this practice more costly than is often realized. Also, autologous blood donation increases the likelihood that the patient will be anemic on the day of surgery, so that he or she may still need allogeneic blood after all, defeating the initial purpose. Despite these limitations, preoperative autologous blood donation remains a useful option for a subset of patients with multiple antibodies for whom donor blood may be difficult to obtain.

Cell salvage

Cell salvage is an innovative technology that recovers the patient’s own blood (after being shed from the surgical incision) for transfusion after filtering and washing. It is particularly well suited to procedures that involve massive blood loss. Cell savage requires technical expertise, however, and involves costs associated with both the machine and disposables.

Restricted postoperative phlebotomy

Phlebotomy accounts for a significant amount of blood loss, especially in intensive care patients with arterial lines. The equivalent of 30% of total blood transfused has been reported to be lost to phlebotomy during an intensive care unit stay.³⁶ Triggers for transfusion cannot be assigned universally based on blood loss from phlebotomy but must consider the patient’s hemodynamic status, cardiac reserve, and other clinical characteristics.

PROMOTING RESPONSIBLE BLOOD PRODUCT USE

Blood is expensive, and in recent years hospitals have experienced increases in the cost of blood and blood products. To promote responsible blood use, we have developed a multipronged approach to blood management at Cleveland Clinic. The program’s cornerstone is increased awareness of the risks associated with blood transfusions. The emphasis is on educating staff physicians and other caregivers about the appropriate use of blood products. We also have implemented a new policy requiring staff authorization for all blood requested in nonemergency situations. Additionally, requests for blood components require adherence to an indication-based ordering process. Finally, data about blood use are shared transparently among physicians, encouraging good clinical practice.

In the first 7 months of the program, we observed decreased utilization of blood products in the inpatient setting. Notably, the reduction in blood use was significantly greater in the surgical population than in the medical population.

CONCULSIONS

Anemia is associated with increased morbidity and mortality in the perioperative setting. Perioperative blood transfusion is one method of raising hemoglobin levels in anemic surgical patients, but it increases perioperative morbidity in the form of acute transfusion reactions, immunosuppression, postoperative infection, and longer hospital stays. Moreover, blood collection continues to lag blood demand. For these reasons, most relevant major medical organizations—including the Association of Blood Banks, the American Red Cross, and the FDA—advise that red blood cell–containing components should not be used to treat anemias that can be corrected with medications. These medical alternatives—all of which can be used in the perioperative setting—include iron supplementation, vitamin B₁₂, and ESAs in select patient groups.

DISCUSSION

Question from the audience: Are there risks involved with autologous blood donation? Are different hemoglobin thresholds used when a patient’s own blood is used?

Dr. Kumar: As I mentioned, preoperative autologous donation is a technique that is less frequently used in our hospital. Autologous transfusion is considered safe only for patients who come to the clinic with normal hemoglobin values. Some patients may not have recovered from their blood loss by the time they come to surgery, so you end up needing to give them more blood because they started out anemic.

Question from the audience: Is there risk to giving patients back their own blood? Do you have to worry about transfusion-induced lung injury, sepsis, or other complications?

Dr. Kumar: As with allogeneic blood, the risk of clerical or clinical error exists with autologous blood: it too needs to be kept on the shelf, taken out, and infused, and the risk of sepsis remains the same.

If this is a typical audience of physicians involved in perioperative care, about 35% to 40% of you have been sued for malpractice and have learned the hard way some of the lessons we will discuss today. This session will begin with an overview of malpractice law and medicolegal principles, after which we will review three real-life malpractice cases and open the floor to the audience for discussion of the lessons these cases can offer.

MALPRACTICE LAWSUITS ARE COMMON, EXPENSIVE, DAMAGING

If a physician practices long enough, lawsuits are nearly inevitable, especially in certain specialties. Surgeons and anesthesiologists are sued about once every 4 to 5 years; internists generally are sued less, averaging once every 7 to 10 years,¹ but hospitalists and others who practice a good deal of perioperative care probably constitute a higher risk pool among internists.

At the same time, it is estimated that only one in eight preventable medical errors committed in hospitals results in a malpractice claim.² From 1995 to 2000, the number of new malpractice claims actually declined by approximately 4%.³

Jury awards can be huge

Fewer than half (42%) of verdicts in malpractice cases are won by plaintiffs.⁴ But when plaintiffs succeed, the awards can be costly: the mean amount of physician malpractice payments in the United States in 2006 (the most recent data available) was $311,965, according to the National Practitioner Data Bank.⁵ Cases that involve a death result in substantially higher payments, averaging $1.4 million.⁴

Lawsuits are traumatic

Even if a physician is covered by good malpractice insurance, a malpractice lawsuit typically changes his or her life. It causes major disruption to the physician’s practice and may damage his or her reputation. Lawsuits cause considerable emotional distress, including a loss of self-esteem, particularly if the physician feels that a mistake was made in the delivery of care.

CATEGORIES OF CLAIMS IN MALPRACTICE LAW

Malpractice law involves torts, which are civil wrongs causing injury to a person or property for which the plaintiff may seek redress through the courts. In general, the plaintiff seeks financial compensation. Practitioners do not go to jail for committing malpractice unless a district attorney decides that the harm was committed intentionally, in which case criminal charges may be brought.

There are many different categories of claims in malpractice law. The most common pertaining to perioperative medicine involve issues surrounding informed consent and medical negligence (the worst form being wrongful death).

Informed consent

Although everyone is familiar with informed consent, details of the process are called into question when something goes wrong. Informed consent is based on the right of patient autonomy: each person has a right to determine what will be done to his or her body, which includes the right to consent to or refuse treatment.

For any procedure, treatment, or medication, patients should be informed about the following:

• The nature of the intervention
• The benefits of the intervention (why it is being recommended)
• Significant risks reasonably expected to exist
• Available alternatives (including “no treatment”).

If possible, it is important that the patient’s family understand the risks involved, because if the patient dies or becomes incapacitated, a family that is surprised by the outcome is more likely to sue.

The standard to which physicians are held in malpractice suits is that of a “reasonable physician” dealing with a “reasonable patient.” Often, a plaintiff claims that he or she did not know that a specific risk was involved, and the doctor claims that he or she spent a “typical” amount of time explaining all the risks. If that amount of time was only a few seconds, that may not pass the “reasonable physician” test, as a jury might conclude that more time may have been necessary.

Negligence and wrongful death

Negligence, including wrongful death, is a very common category of claim. The plaintiff generally must demonstrate four elements in negligence claims:

• The provider had a duty to the patient
• The duty was breached
• An injury occurred
• The breach of duty was a “proximate cause” of the injury.

Duty arises from the physician-patient relationship: any person whose name is on the medical chart essentially has a duty to the patient and can be brought into the case, even if the involvement was only peripheral.

Breach of duty. Determining whether a breach of duty occurred often involves a battle of medical experts. The standard of care is defined as what a reasonable practitioner would do under the same or similar circumstances, assuming similar training and background. The jury decides whether the physician met the standard of care based on testimony from experts.

The Latin phrase res ipsa loquitur means “the thing speaks for itself.” In surgery, the classic example is if an instrument or a towel were accidentally left in a patient. In such a situation, the breach of duty is obvious, so the strategy of the defense generally must be to show that the patient was not harmed by the breach.

Injury. The concept of injury can be broad and often depends on distinguishing bad practice from a bad or unfortunate outcome. For instance, a patient who suffered multisystem trauma but whose life was saved by medical intervention could sue if he ended up with paresthesia in the foot afterwards. An expert may be called to help determine whether or not the complication is reasonable for the particular medical situation. Patient expectations usually factor prominently into questions of injury.

Proximate cause often enters into situations involving wrongful death. A clear understanding of the cause of death or evidence from an autopsy is not necessarily required for a plaintiff to argue that malpractice was a proximate cause of death. A plaintiff’s attorney will often speculate why a patient died, and because the plaintiff’s burden of proof is so low (see next paragraph), it may not help the defense to argue that it is pure speculation that a particular event was related to the death. 

A low burden of proof

In a civil tort, the burden of proof is established by a “preponderance of the evidence,” meaning that the allegation is “more likely than not.” This is a much lower standard than the “beyond a reasonable doubt” threshold used for criminal proceedings. In other words, the plaintiff has to show only that the chance that malpractice occurred was greater than 50%. 

Three types of damages

Potential damages (financial compensation) in malpractice suits fall into three categories:

• Economic, or the monetary costs of an injury (eg, medical bills or loss of income)
• Noneconomic (eg, pain and suffering, loss of ability to have sex)
• Punitive, or damages to punish a defendant for willful and wanton conduct.

Punitive damages are generally not covered by malpractice insurance policies and are only rarely involved in cases against an individual physician. They are more often awarded when deep pockets are perceived to be involved, such as in a case against a hospital system or an insurance company, and when the jury wants to punish the entity for doing something that was believed to be willful.

Regardless of the circumstances, communication is probably the most important factor determining whether a physician will be sued. Sometimes a doctor does everything right medically but gets sued because of lack of communication with the patient. Conversely, many of us know of veteran physicians who still practice medicine as they did 35 years ago but are never sued because they have a great rapport with their patients and their patients love them for it.

The importance of careful charting also cannot be overemphasized. In malpractice cases, experts for the plaintiff will comb through the medical records and be sure to notice if something is missing. The plaintiff also benefits enormously if, for instance, nurses documented that they paged the doctor many times over a 3-day period and got no response.

CASE 1: PATIENT DIES DURING PREOPERATIVE STRESS TEST FOR KNEE SURGERY

A 65-year-old man with New York Heart Association class III cardiac disease (marked limitation of physical activity) is scheduled for a total knee arthroplasty and is seen at the preoperative testing center. His past medical history includes coronary artery disease, chronic obstructive pulmonary disease, hypertension, and prior repair of an abdominal aortic aneurysm. He is referred for a preoperative stress test.

Dobutamine stress echocardiography is performed. His target heart rate is reached at 132 beats per minute with sporadic premature ventricular contractions. Toward the end of the test, he complains of shortness of breath and chest pain. The test is terminated, and the patient goes into ventricular tachycardia and then ventricular fibrillation. Despite resuscitative efforts, he dies.

Dr. Michota: From the family’s perspective, this patient had come for quality-of-life–enhancing surgery. They were looking forward to him getting a new knee so he could play golf again when he retired. The doctor convinced them that he needed a stress test first, which ends up killing him. Mr. Donnelly, as a lawyer, would you want to be the plaintiff’s attorney in this case?

Mr. Donnelly: Very much so. The family never contemplated that their loved one would die from this procedure. The first issue would be whether or not the possibility of complications or death from the stress test had been discussed with the patient or his family.

Consent must be truly ‘informed’ and documented

Dr. Michota: How many of our audience members who do preoperative assessments and refer patients for stress testing can recall a conversation with a patient that included the comment, “You may die from getting this test”? Before this case occurred, I never brought up this possibility, but I do now. This case illustrates how important expectations are.

Comment from the audience: I think you have to be careful of your own bias about risks. You might say to the patient, “There’s a risk that you’ll have an arrhythmia and die,” but if you also tell him, “I’ve never seen that happen during a stress test in my 10 years of practice,” you’ve biased the informed consent. The family can say, “Well, he basically told us that it wasn’t going to happen; he’d never seen a case of it.”

Dr. Michota: Are there certain things we shouldn’t say? Surely you should never promise somebody a good outcome by saying that certain rare events never happen.

Mr. Donnelly: That’s true. You can give percentages. You might say, “I’m letting you know there’s a possibility that you could die from this, but it’s a low percentage risk.” That way, you are informing the patient. This relates to the “reasonable physician” and “reasonable patient” standard. You are expected to do what is reasonable.

Is a signed consent form adequate defense?

Dr. Michota: What should the defense team do now? Let’s say informed consent was obtained and documented at the stress lab. The patient signed a form that listed death as a risk, but no family members were present. Is this an adequate defense?

Mr. Donnelly: It depends on whether the patient understood what was on the form and had the opportunity to ask questions.

Dr. Michota: So the form means nothing?

Mr. Donnelly: If he didn’t understand it, that is correct.

Dr. Michota: We thought he understood it. Can’t we just say, “Of course he understood it—he signed it.”

Mr. Donnelly: No. Keep in mind that most jurors have been patients at one time or another. There may be a perception that physicians are rushed or don’t have time to answer questions. Communication is really important here.

Dr. Michota: But surely there’s a physician on the jury who can help talk to the other jurors about how it really works.

Mr. Donnelly: No, a “jury of peers” is not a jury box of physicians. The plaintiff’s attorneys tend to exclude scientists and other educated professionals from the jury; they don’t want jurors who are accustomed to holding people to certain standards. They prefer young, impressionable people who wouldn’t think twice about awarding somebody $20 million.

Question from the audience: Who should have obtained informed consent for this patient—the doctor who referred him for the stress test or the cardiologist who conducted the test? Sometimes I have to get informed consent for specialty procedures that I myself do not understand very well. Could I be considered culpable even though I’m not the one doing the procedure? I can imagine an attorney asking, “Doctor, are you a cardiologist? How many of these tests do you do? Why are you the one doing the informed consent? Did the patient really understand the effects of the test? Do you really understand them?”

Dr. Michota: That question is even more pertinent if the patient is referred to another institution covered under different malpractice insurance. You can bet the other provider will try to blame you if something goes wrong.

Mr. Donnelly: In an ideal world, both the referring physician and the physician who does the test discuss the risks, benefits, and alternatives, and answer all questions that the patient and family have. The discussion is properly documented in the medical record.

Question from the audience: Can you address the issue of supervision? What is the liability of a resident or intern in doing the informed consent?

Mr. Donnelly: The attending physician is usually responsible for everything that a resident does. I would prefer that the attending obtain the informed consent.

Dr. Michota: But our fellows and second-year postgraduate residents are independent licensed practitioners in Ohio. Does letting them handle informed consent pose a danger to a defense team’s legal case?

Mr. Donnelly: It’s not necessarily a danger medically, but it gives the plaintiff something to talk about. They will ignore the fact that an independent licensed practitioner obtained the informed consent. They will simply focus on the fact that the physician was a resident or fellow. They will claim, “They had this young, inexperienced doctor give the informed consent when there were staff physicians with 20 years of experience who should have done it.” Plaintiffs will attempt to get a lot of mileage out of these minor issues.

Question from the audience: At our institution, the physician is present with the technician, so that when the physician obtains consent, the technician signs as a witness. The bottom of the long form basically says, “By signing this form, I attest that the physician performing the test has informed me of the benefits and risks of this test, and I agree to go ahead. I fully understand the implications of the test.” Does that have value in the eyes of the law?

Mr. Donnelly: That’s a great informed consent process and will have great value. That said, you can still get sued, because you can get sued for anything. But the jury ultimately decides, and odds are that with a process like yours they will conclude that the patient knew all the risks and benefits and alternatives because he or she signed the form and the doctor documented that everything was discussed.

Confidentiality vs family involvement

Comment from the audience: I’m struck by the comments that informed consent is supposed to be with the family so that there will be living witnesses in case the patient dies. According to Health Insurance Portability and Accountability Act (HIPAA) regulations, we have to be very careful to maintain confidentiality. For a competent patient, medical discussions are private unless specific permission has been obtained to involve the family.

Mr. Donnelly: Yes, we’ve assumed that the patient gave permission to discuss these issues with his family. If the patient does not want that, obviously you can’t include the family because of HIPAA regulations.

Question from the audience: Should we routinely ask a patient to involve the family in an informed consent in case something goes wrong?

Mr. Donnelly: No. In general, it’s appropriate only if the family is already present.

Dr. Michota: Keep in mind that there’s nothing you can do to completely prevent being sued. You can do everything right and still get sued. If you’re following good clinical practice and a patient doesn’t want to involve the family, all you can do is document your discussion and that you believed the patient understood the risks of the procedure.

Question from the audience: Do you consider a patient’s decision-making capacity for informed consent? Should physicians document it prior to obtaining consent? A plaintiff can always claim that an elderly patient did not understand.

Mr. Donnelly: I have never seen specific documentation that a patient had capacity to consent, but it’s a good idea for a borderline case. For such a case, it’s especially important to involve the family and document, “I discussed the matter with this elderly patient and her husband and three daughters.” You could also get a psychiatric consult or a social worker to help determine whether a patient has the capacity to make legal and medical decisions.

CASE 2: FATAL POSTSURGICAL MI RAISES QUESTIONS ABOUT THE PREOP EVALUATION

A 75-year-old man with rectal cancer presents for colorectal surgery. He has a remote cardiac history but exercises regularly and has a good functional classification without symptoms. The surgery is uneventful, but the patient develops hypotension in the postanesthesia care unit. He improves the next morning and goes to the colorectal surgery ward. Internal bleeding occurs but initially goes unrecognized; on postoperative day 2, his hemoglobin is found to be 2 g/dL and he is transferred to the intensive care unit, then back to the operating room, where he suffers cardiac arrest. He is revived but dies 2 weeks later. Autopsy reveals that he died of a myocardial infarction (MI).

Dr. Michota: The complaint in this case is that the patient did not receive a proper preoperative evaluation because no cardiac workup was done. As the hypothetical defense attorney, do you feel this case has merit? The patient most likely had an MI from demand ischemia due to hemorrhage, but does this have anything to do with not having a cardiac workup?

Mr. Donnelly: You as the physician are saying that even if he had an electrocardiogram (ECG), it is likely that nothing would have been determined. The cardiac problems he had prior to the surgery in question were well controlled, occurred in the distant past, and may not have affected the outcome. Maybe his remote cardiac problems were irrelevant and something else caused the MI that killed him. Nevertheless, the fact that the ECG wasn’t done still could be a major issue for the plaintiff’s attorney. After the fact, it seems like a no-brainer that an ECG should have been done in a case like this, and it’s easy for the plaintiff to argue that it might have detected something. The defense has to keep reminding the jury that the case cannot be looked at retrospectively, and that’s a tall order.

Dr. Michota: This case shows that even in the context of high-quality care, such things can happen. We have spent a lot of time at this summit talking about guidelines. But at the end of the day, if somebody dies perioperatively of an MI, the family may start looking for blame and any plaintiff’s attorney will go through the record to see if a preoperative ECG was done. If it wasn’t, a suit will get filed.

Question from the audience: Even if the physician had done the ECG, how do you know the plaintiff’s attorney wouldn’t attack him for not ordering a stress test? And if he had done a stress test, then they’d ask why he didn’t order a catheterization. Where is it going to end?

Dr. Michota: You make a good point. The best way for physicians to protect themselves is to follow the four Cs mentioned earlier: competent care, communication, compassion, and charting. After I learned about this case, the next time I was in the clinic and didn’t order an ECG, I asked the patient, “Did you expect that we would do an ECG here today?” When he responded that he did, I talked to him about how it wasn’t indicated and probably would not change management. So that level of communication can sometimes prevent a lawsuit that might stem from a patient not feeling informed. I’m not suggesting that you spend hours explaining details with each patient, but it’s good to be aware that cases like this happen and how you can reduce their likelihood.

Battles of the experts

Question from the audience: Exactly what standard is applied when the “standard of care” is determined in a court? For instance, my hospital may routinely order stress tests, whereas the American College of Cardiology and American Heart Association (ACC/AHA) guidelines are more restrictive in recommending when a stress test is indicated. Which standard would apply in court?

Dr. Michota: It’s easy to find a plaintiff’s expert who will say just about anything. If you claim that everybody gets a stress test at your community hospital and a patient dies during the stress test, the plaintiff’s team will find an expert to say, “That was an unnecessary test and posed an unnecessary risk.” If you’re in a setting where stress tests are rarely done for preoperative evaluation, they’ll find an expert to say, “Stress testing was available; it should have been done.”

This is when the battles of the experts occur. If you have a superstar physician on your defense team, the plaintiff will have to find someone of equal pedigree who can argue against him or her. Sometimes cases go away because the defense lines up amazing experts and the plaintiffs lose their stomach for the money it would take to bring the case forward. But usually cases do not involve that caliber of experts; most notables in the field are academic physicians who don’t do this type of work. Usually you get busy physicians who spend 75% of their time in clinical practice and seem smart enough to impress the jury. Although they can say things that aren’t even factual, they can sway the jury. 

Question from the audience: I would not have ordered a preoperative ECG on this healthy 75-year-old, but one of the experts at this summit said that he would get a baseline ECG for such a case. How are differences like these reconciled in the legal context?

Dr. Michota: The standard to which we are held is that of a reasonable physician. Can you show that your approach was a reasonable one? Can you say, “I didn’t order the ECG for the following reasons, and I discussed the issue with the patient”? Or alternately, “An ECG was ordered for the following reasons, and I discussed it with the patient”? The jury will want to know whether the care that was provided was reasonable.

Costs and consequences of being sued

Question from the audience: What does it cost to mount a defense in a malpractice trial?

Mr. Donnelly: You can easily spend more than $100,000 to go through a trial. Plaintiffs typically have three or four experts in various cities across the country, and you have to pay your lawyers to travel to those cities and take the depositions. And delays often occur. Cases get filed, dismissed, and refiled. A lot of the work that the lawyers did to prepare for the trial will have to be redone for a second, third, or fourth time as new dates for the trial are set. There are many unforeseen costs.

Dr. Michota: Let’s say the physician who did the preoperative evaluation in this case was not affiliated with the hospital and wasn’t involved in the surgery or any of the postoperative monitoring and management, which we see may have been questionable. This physician might get pulled into the case anyway because he didn’t order an ECG in the preoperative evaluation. Although an ECG wasn’t recommended in this case by the ACC/AHA guidelines, this doctor is looking at spending considerable time, energy, and money to defend himself. What if his attorney recommends that he settle for a nominal amount—say, $25,000—because it’s cheaper and easier? Are there repercussions for him as a physician when he pays out a settlement under his name?

Mr. Donnelly: Absolutely. He will be reported to the National Practitioner Data Bank, and when he renews his license or applies for a license to practice in another state, he must disclose that he has been sued and paid a settlement. The new consumer-targeted public reporting Web sites will also publicize this information. It is like a black mark against this doctor even though he never admitted any liability.

CASE 3: A CLEAR CASE OF NEGLIGENCE―WHO IS RESPONSIBLE

A 67-year-old man undergoes a laminectomy in the hospital. He develops shortness of breath postoperatively and is seen by the hospitalist team. He is started on full-dose weight-adjusted low-molecular-weight heparin (LMWH) for possible pulmonary embolism or acute coronary syndrome. His symptoms resolve and his workup is negative. It is a holiday weekend. The consultants sign off but do not stop the full-dose LMWH. The patient is discharged to the rehabilitation unit by the surgeon and the surgeon’s assistant, who include all the medications at discharge, including the full-dose LMWH. The patient is admitted to a subacute nursing facility, where the physiatrist transfers to the chart all the medications on which the patient was discharged.

The patient does well until postoperative day 7, when he develops urinary retention and can’t move his legs. At this point, someone finally questions why he is on the LMWH, and it is stopped. The patient undergoes emergency surgery to evacuate a huge spinal hematoma, but his neurologic function never recovers.

Dr. Michota: I think most of us would agree that there was negligence here. I bet a plaintiff’s attorney would love to have this case.

Mr. Donnelly: Absolutely. The patient can no longer walk, so it’s already a high-value case. It would be even more so if we supposed that the patient were only 45 years old and a corporate executive. That would make it a really high-value case.

Dr. Michota: What do you mean? Does a patient’s age or economic means matter to a plaintiff’s attorney?

Mr. Donnelly: Of course. For a plaintiff’s attorney, it’s always nice to have a case like this where there’s negligence, but the high-dollar cases typically involve a likable plaintiff who is a high wage earner with a good family. A plaintiff’s lawyer will take a case that may not be so strong on evidence of negligence if it’s likely that a jury will like the plaintiff and his or her family. Kids always help to sway a jury—jurors will feel sorry for them and want to help them. This case even has two surgeries, so the family’s medical bills will be especially high. It’s a great case for a plaintiff’s attorney.

Who’s at fault?

Dr. Michota: Let’s look at a few more case details. Once the various doctors involved in this case realized what happened, they got nervous and engaged in finger-pointing. The surgeons felt that the hospitalists should have stopped the LMWH. The hospitalists claimed that since they had signed off, the surgeons should have stopped it. The physiatrist said, “Who am I to decide to stop medications? I assumed that the hospital physicians checked the medications before sending the patient to the rehab facility.”

Interestingly, a hospitalist went back and made a chart entry after the second surgery. He wrote, “Late chart entry. Discussion with surgeon regarding LMWH. I told him to stop it.” Does that make him free and clear?

Mr. Donnelly: Actually, the hospitalist just shot his credibility, and now the jury is really angry. The dollar value of the case has just gone up.

Dr. Michota: Okay, suppose the hospitalist wouldn’t do something that obvious. Instead, he goes back to the chart after the fact, finds the same color pen as the entry at the time, and writes, “Patient is okay. Please stop LMWH,” and signs his name. Is there any way anyone is going to be able to figure that out?

Mr. Donnelly: All the other doctors and nurses will testify that the note was not in the chart before. The plaintiff will hire a handwriting expert and look at the different impressions on the paper, the inks, and the style of writing. Now the hospitalist has really escalated the situation and is liable for punitive damages, which will come out of his own pocket, since malpractice insurance doesn’t cover punitive damages. His license may be threatened. The jury will really be angered, and the plaintiff’s lawyer will love stoking the situation.

If this is a typical audience of physicians involved in perioperative care, about 35% to 40% of you have been sued for malpractice and have learned the hard way some of the lessons we will discuss today. This session will begin with an overview of malpractice law and medicolegal principles, after which we will review three real-life malpractice cases and open the floor to the audience for discussion of the lessons these cases can offer.

MALPRACTICE LAWSUITS ARE COMMON, EXPENSIVE, DAMAGING

If a physician practices long enough, lawsuits are nearly inevitable, especially in certain specialties. Surgeons and anesthesiologists are sued about once every 4 to 5 years; internists generally are sued less, averaging once every 7 to 10 years,¹ but hospitalists and others who practice a good deal of perioperative care probably constitute a higher risk pool among internists.

At the same time, it is estimated that only one in eight preventable medical errors committed in hospitals results in a malpractice claim.² From 1995 to 2000, the number of new malpractice claims actually declined by approximately 4%.³

Jury awards can be huge

Fewer than half (42%) of verdicts in malpractice cases are won by plaintiffs.⁴ But when plaintiffs succeed, the awards can be costly: the mean amount of physician malpractice payments in the United States in 2006 (the most recent data available) was $311,965, according to the National Practitioner Data Bank.⁵ Cases that involve a death result in substantially higher payments, averaging $1.4 million.⁴

Lawsuits are traumatic

Even if a physician is covered by good malpractice insurance, a malpractice lawsuit typically changes his or her life. It causes major disruption to the physician’s practice and may damage his or her reputation. Lawsuits cause considerable emotional distress, including a loss of self-esteem, particularly if the physician feels that a mistake was made in the delivery of care.

CATEGORIES OF CLAIMS IN MALPRACTICE LAW

Malpractice law involves torts, which are civil wrongs causing injury to a person or property for which the plaintiff may seek redress through the courts. In general, the plaintiff seeks financial compensation. Practitioners do not go to jail for committing malpractice unless a district attorney decides that the harm was committed intentionally, in which case criminal charges may be brought.

There are many different categories of claims in malpractice law. The most common pertaining to perioperative medicine involve issues surrounding informed consent and medical negligence (the worst form being wrongful death).

Informed consent

Although everyone is familiar with informed consent, details of the process are called into question when something goes wrong. Informed consent is based on the right of patient autonomy: each person has a right to determine what will be done to his or her body, which includes the right to consent to or refuse treatment.

For any procedure, treatment, or medication, patients should be informed about the following:

• The nature of the intervention
• The benefits of the intervention (why it is being recommended)
• Significant risks reasonably expected to exist
• Available alternatives (including “no treatment”).

If possible, it is important that the patient’s family understand the risks involved, because if the patient dies or becomes incapacitated, a family that is surprised by the outcome is more likely to sue.

The standard to which physicians are held in malpractice suits is that of a “reasonable physician” dealing with a “reasonable patient.” Often, a plaintiff claims that he or she did not know that a specific risk was involved, and the doctor claims that he or she spent a “typical” amount of time explaining all the risks. If that amount of time was only a few seconds, that may not pass the “reasonable physician” test, as a jury might conclude that more time may have been necessary.

Negligence and wrongful death

Negligence, including wrongful death, is a very common category of claim. The plaintiff generally must demonstrate four elements in negligence claims:

• The provider had a duty to the patient
• The duty was breached
• An injury occurred
• The breach of duty was a “proximate cause” of the injury.

Duty arises from the physician-patient relationship: any person whose name is on the medical chart essentially has a duty to the patient and can be brought into the case, even if the involvement was only peripheral.

Breach of duty. Determining whether a breach of duty occurred often involves a battle of medical experts. The standard of care is defined as what a reasonable practitioner would do under the same or similar circumstances, assuming similar training and background. The jury decides whether the physician met the standard of care based on testimony from experts.

The Latin phrase res ipsa loquitur means “the thing speaks for itself.” In surgery, the classic example is if an instrument or a towel were accidentally left in a patient. In such a situation, the breach of duty is obvious, so the strategy of the defense generally must be to show that the patient was not harmed by the breach.

Injury. The concept of injury can be broad and often depends on distinguishing bad practice from a bad or unfortunate outcome. For instance, a patient who suffered multisystem trauma but whose life was saved by medical intervention could sue if he ended up with paresthesia in the foot afterwards. An expert may be called to help determine whether or not the complication is reasonable for the particular medical situation. Patient expectations usually factor prominently into questions of injury.

Proximate cause often enters into situations involving wrongful death. A clear understanding of the cause of death or evidence from an autopsy is not necessarily required for a plaintiff to argue that malpractice was a proximate cause of death. A plaintiff’s attorney will often speculate why a patient died, and because the plaintiff’s burden of proof is so low (see next paragraph), it may not help the defense to argue that it is pure speculation that a particular event was related to the death. 

A low burden of proof

In a civil tort, the burden of proof is established by a “preponderance of the evidence,” meaning that the allegation is “more likely than not.” This is a much lower standard than the “beyond a reasonable doubt” threshold used for criminal proceedings. In other words, the plaintiff has to show only that the chance that malpractice occurred was greater than 50%. 

Three types of damages

Potential damages (financial compensation) in malpractice suits fall into three categories:

• Economic, or the monetary costs of an injury (eg, medical bills or loss of income)
• Noneconomic (eg, pain and suffering, loss of ability to have sex)
• Punitive, or damages to punish a defendant for willful and wanton conduct.

Punitive damages are generally not covered by malpractice insurance policies and are only rarely involved in cases against an individual physician. They are more often awarded when deep pockets are perceived to be involved, such as in a case against a hospital system or an insurance company, and when the jury wants to punish the entity for doing something that was believed to be willful.

Regardless of the circumstances, communication is probably the most important factor determining whether a physician will be sued. Sometimes a doctor does everything right medically but gets sued because of lack of communication with the patient. Conversely, many of us know of veteran physicians who still practice medicine as they did 35 years ago but are never sued because they have a great rapport with their patients and their patients love them for it.

The importance of careful charting also cannot be overemphasized. In malpractice cases, experts for the plaintiff will comb through the medical records and be sure to notice if something is missing. The plaintiff also benefits enormously if, for instance, nurses documented that they paged the doctor many times over a 3-day period and got no response.

CASE 1: PATIENT DIES DURING PREOPERATIVE STRESS TEST FOR KNEE SURGERY

A 65-year-old man with New York Heart Association class III cardiac disease (marked limitation of physical activity) is scheduled for a total knee arthroplasty and is seen at the preoperative testing center. His past medical history includes coronary artery disease, chronic obstructive pulmonary disease, hypertension, and prior repair of an abdominal aortic aneurysm. He is referred for a preoperative stress test.

Dobutamine stress echocardiography is performed. His target heart rate is reached at 132 beats per minute with sporadic premature ventricular contractions. Toward the end of the test, he complains of shortness of breath and chest pain. The test is terminated, and the patient goes into ventricular tachycardia and then ventricular fibrillation. Despite resuscitative efforts, he dies.

Dr. Michota: From the family’s perspective, this patient had come for quality-of-life–enhancing surgery. They were looking forward to him getting a new knee so he could play golf again when he retired. The doctor convinced them that he needed a stress test first, which ends up killing him. Mr. Donnelly, as a lawyer, would you want to be the plaintiff’s attorney in this case?

Mr. Donnelly: Very much so. The family never contemplated that their loved one would die from this procedure. The first issue would be whether or not the possibility of complications or death from the stress test had been discussed with the patient or his family.

Consent must be truly ‘informed’ and documented

Dr. Michota: How many of our audience members who do preoperative assessments and refer patients for stress testing can recall a conversation with a patient that included the comment, “You may die from getting this test”? Before this case occurred, I never brought up this possibility, but I do now. This case illustrates how important expectations are.

Comment from the audience: I think you have to be careful of your own bias about risks. You might say to the patient, “There’s a risk that you’ll have an arrhythmia and die,” but if you also tell him, “I’ve never seen that happen during a stress test in my 10 years of practice,” you’ve biased the informed consent. The family can say, “Well, he basically told us that it wasn’t going to happen; he’d never seen a case of it.”

Dr. Michota: Are there certain things we shouldn’t say? Surely you should never promise somebody a good outcome by saying that certain rare events never happen.

Mr. Donnelly: That’s true. You can give percentages. You might say, “I’m letting you know there’s a possibility that you could die from this, but it’s a low percentage risk.” That way, you are informing the patient. This relates to the “reasonable physician” and “reasonable patient” standard. You are expected to do what is reasonable.

Is a signed consent form adequate defense?

Dr. Michota: What should the defense team do now? Let’s say informed consent was obtained and documented at the stress lab. The patient signed a form that listed death as a risk, but no family members were present. Is this an adequate defense?

Mr. Donnelly: It depends on whether the patient understood what was on the form and had the opportunity to ask questions.

Dr. Michota: So the form means nothing?

Mr. Donnelly: If he didn’t understand it, that is correct.

Dr. Michota: We thought he understood it. Can’t we just say, “Of course he understood it—he signed it.”

Mr. Donnelly: No. Keep in mind that most jurors have been patients at one time or another. There may be a perception that physicians are rushed or don’t have time to answer questions. Communication is really important here.

Dr. Michota: But surely there’s a physician on the jury who can help talk to the other jurors about how it really works.

Mr. Donnelly: No, a “jury of peers” is not a jury box of physicians. The plaintiff’s attorneys tend to exclude scientists and other educated professionals from the jury; they don’t want jurors who are accustomed to holding people to certain standards. They prefer young, impressionable people who wouldn’t think twice about awarding somebody $20 million.

Question from the audience: Who should have obtained informed consent for this patient—the doctor who referred him for the stress test or the cardiologist who conducted the test? Sometimes I have to get informed consent for specialty procedures that I myself do not understand very well. Could I be considered culpable even though I’m not the one doing the procedure? I can imagine an attorney asking, “Doctor, are you a cardiologist? How many of these tests do you do? Why are you the one doing the informed consent? Did the patient really understand the effects of the test? Do you really understand them?”

Dr. Michota: That question is even more pertinent if the patient is referred to another institution covered under different malpractice insurance. You can bet the other provider will try to blame you if something goes wrong.

Mr. Donnelly: In an ideal world, both the referring physician and the physician who does the test discuss the risks, benefits, and alternatives, and answer all questions that the patient and family have. The discussion is properly documented in the medical record.

Question from the audience: Can you address the issue of supervision? What is the liability of a resident or intern in doing the informed consent?

Mr. Donnelly: The attending physician is usually responsible for everything that a resident does. I would prefer that the attending obtain the informed consent.

Dr. Michota: But our fellows and second-year postgraduate residents are independent licensed practitioners in Ohio. Does letting them handle informed consent pose a danger to a defense team’s legal case?

Mr. Donnelly: It’s not necessarily a danger medically, but it gives the plaintiff something to talk about. They will ignore the fact that an independent licensed practitioner obtained the informed consent. They will simply focus on the fact that the physician was a resident or fellow. They will claim, “They had this young, inexperienced doctor give the informed consent when there were staff physicians with 20 years of experience who should have done it.” Plaintiffs will attempt to get a lot of mileage out of these minor issues.

Question from the audience: At our institution, the physician is present with the technician, so that when the physician obtains consent, the technician signs as a witness. The bottom of the long form basically says, “By signing this form, I attest that the physician performing the test has informed me of the benefits and risks of this test, and I agree to go ahead. I fully understand the implications of the test.” Does that have value in the eyes of the law?

Mr. Donnelly: That’s a great informed consent process and will have great value. That said, you can still get sued, because you can get sued for anything. But the jury ultimately decides, and odds are that with a process like yours they will conclude that the patient knew all the risks and benefits and alternatives because he or she signed the form and the doctor documented that everything was discussed.

Confidentiality vs family involvement

Comment from the audience: I’m struck by the comments that informed consent is supposed to be with the family so that there will be living witnesses in case the patient dies. According to Health Insurance Portability and Accountability Act (HIPAA) regulations, we have to be very careful to maintain confidentiality. For a competent patient, medical discussions are private unless specific permission has been obtained to involve the family.

Mr. Donnelly: Yes, we’ve assumed that the patient gave permission to discuss these issues with his family. If the patient does not want that, obviously you can’t include the family because of HIPAA regulations.

Question from the audience: Should we routinely ask a patient to involve the family in an informed consent in case something goes wrong?

Mr. Donnelly: No. In general, it’s appropriate only if the family is already present.

Dr. Michota: Keep in mind that there’s nothing you can do to completely prevent being sued. You can do everything right and still get sued. If you’re following good clinical practice and a patient doesn’t want to involve the family, all you can do is document your discussion and that you believed the patient understood the risks of the procedure.

Question from the audience: Do you consider a patient’s decision-making capacity for informed consent? Should physicians document it prior to obtaining consent? A plaintiff can always claim that an elderly patient did not understand.

Mr. Donnelly: I have never seen specific documentation that a patient had capacity to consent, but it’s a good idea for a borderline case. For such a case, it’s especially important to involve the family and document, “I discussed the matter with this elderly patient and her husband and three daughters.” You could also get a psychiatric consult or a social worker to help determine whether a patient has the capacity to make legal and medical decisions.

CASE 2: FATAL POSTSURGICAL MI RAISES QUESTIONS ABOUT THE PREOP EVALUATION

A 75-year-old man with rectal cancer presents for colorectal surgery. He has a remote cardiac history but exercises regularly and has a good functional classification without symptoms. The surgery is uneventful, but the patient develops hypotension in the postanesthesia care unit. He improves the next morning and goes to the colorectal surgery ward. Internal bleeding occurs but initially goes unrecognized; on postoperative day 2, his hemoglobin is found to be 2 g/dL and he is transferred to the intensive care unit, then back to the operating room, where he suffers cardiac arrest. He is revived but dies 2 weeks later. Autopsy reveals that he died of a myocardial infarction (MI).

Dr. Michota: The complaint in this case is that the patient did not receive a proper preoperative evaluation because no cardiac workup was done. As the hypothetical defense attorney, do you feel this case has merit? The patient most likely had an MI from demand ischemia due to hemorrhage, but does this have anything to do with not having a cardiac workup?

Mr. Donnelly: You as the physician are saying that even if he had an electrocardiogram (ECG), it is likely that nothing would have been determined. The cardiac problems he had prior to the surgery in question were well controlled, occurred in the distant past, and may not have affected the outcome. Maybe his remote cardiac problems were irrelevant and something else caused the MI that killed him. Nevertheless, the fact that the ECG wasn’t done still could be a major issue for the plaintiff’s attorney. After the fact, it seems like a no-brainer that an ECG should have been done in a case like this, and it’s easy for the plaintiff to argue that it might have detected something. The defense has to keep reminding the jury that the case cannot be looked at retrospectively, and that’s a tall order.

Dr. Michota: This case shows that even in the context of high-quality care, such things can happen. We have spent a lot of time at this summit talking about guidelines. But at the end of the day, if somebody dies perioperatively of an MI, the family may start looking for blame and any plaintiff’s attorney will go through the record to see if a preoperative ECG was done. If it wasn’t, a suit will get filed.

Question from the audience: Even if the physician had done the ECG, how do you know the plaintiff’s attorney wouldn’t attack him for not ordering a stress test? And if he had done a stress test, then they’d ask why he didn’t order a catheterization. Where is it going to end?

Dr. Michota: You make a good point. The best way for physicians to protect themselves is to follow the four Cs mentioned earlier: competent care, communication, compassion, and charting. After I learned about this case, the next time I was in the clinic and didn’t order an ECG, I asked the patient, “Did you expect that we would do an ECG here today?” When he responded that he did, I talked to him about how it wasn’t indicated and probably would not change management. So that level of communication can sometimes prevent a lawsuit that might stem from a patient not feeling informed. I’m not suggesting that you spend hours explaining details with each patient, but it’s good to be aware that cases like this happen and how you can reduce their likelihood.

Battles of the experts

Question from the audience: Exactly what standard is applied when the “standard of care” is determined in a court? For instance, my hospital may routinely order stress tests, whereas the American College of Cardiology and American Heart Association (ACC/AHA) guidelines are more restrictive in recommending when a stress test is indicated. Which standard would apply in court?

Dr. Michota: It’s easy to find a plaintiff’s expert who will say just about anything. If you claim that everybody gets a stress test at your community hospital and a patient dies during the stress test, the plaintiff’s team will find an expert to say, “That was an unnecessary test and posed an unnecessary risk.” If you’re in a setting where stress tests are rarely done for preoperative evaluation, they’ll find an expert to say, “Stress testing was available; it should have been done.”

This is when the battles of the experts occur. If you have a superstar physician on your defense team, the plaintiff will have to find someone of equal pedigree who can argue against him or her. Sometimes cases go away because the defense lines up amazing experts and the plaintiffs lose their stomach for the money it would take to bring the case forward. But usually cases do not involve that caliber of experts; most notables in the field are academic physicians who don’t do this type of work. Usually you get busy physicians who spend 75% of their time in clinical practice and seem smart enough to impress the jury. Although they can say things that aren’t even factual, they can sway the jury. 

Question from the audience: I would not have ordered a preoperative ECG on this healthy 75-year-old, but one of the experts at this summit said that he would get a baseline ECG for such a case. How are differences like these reconciled in the legal context?

Dr. Michota: The standard to which we are held is that of a reasonable physician. Can you show that your approach was a reasonable one? Can you say, “I didn’t order the ECG for the following reasons, and I discussed the issue with the patient”? Or alternately, “An ECG was ordered for the following reasons, and I discussed it with the patient”? The jury will want to know whether the care that was provided was reasonable.

Costs and consequences of being sued

Question from the audience: What does it cost to mount a defense in a malpractice trial?

Mr. Donnelly: You can easily spend more than $100,000 to go through a trial. Plaintiffs typically have three or four experts in various cities across the country, and you have to pay your lawyers to travel to those cities and take the depositions. And delays often occur. Cases get filed, dismissed, and refiled. A lot of the work that the lawyers did to prepare for the trial will have to be redone for a second, third, or fourth time as new dates for the trial are set. There are many unforeseen costs.

Dr. Michota: Let’s say the physician who did the preoperative evaluation in this case was not affiliated with the hospital and wasn’t involved in the surgery or any of the postoperative monitoring and management, which we see may have been questionable. This physician might get pulled into the case anyway because he didn’t order an ECG in the preoperative evaluation. Although an ECG wasn’t recommended in this case by the ACC/AHA guidelines, this doctor is looking at spending considerable time, energy, and money to defend himself. What if his attorney recommends that he settle for a nominal amount—say, $25,000—because it’s cheaper and easier? Are there repercussions for him as a physician when he pays out a settlement under his name?

Mr. Donnelly: Absolutely. He will be reported to the National Practitioner Data Bank, and when he renews his license or applies for a license to practice in another state, he must disclose that he has been sued and paid a settlement. The new consumer-targeted public reporting Web sites will also publicize this information. It is like a black mark against this doctor even though he never admitted any liability.

CASE 3: A CLEAR CASE OF NEGLIGENCE―WHO IS RESPONSIBLE

A 67-year-old man undergoes a laminectomy in the hospital. He develops shortness of breath postoperatively and is seen by the hospitalist team. He is started on full-dose weight-adjusted low-molecular-weight heparin (LMWH) for possible pulmonary embolism or acute coronary syndrome. His symptoms resolve and his workup is negative. It is a holiday weekend. The consultants sign off but do not stop the full-dose LMWH. The patient is discharged to the rehabilitation unit by the surgeon and the surgeon’s assistant, who include all the medications at discharge, including the full-dose LMWH. The patient is admitted to a subacute nursing facility, where the physiatrist transfers to the chart all the medications on which the patient was discharged.

The patient does well until postoperative day 7, when he develops urinary retention and can’t move his legs. At this point, someone finally questions why he is on the LMWH, and it is stopped. The patient undergoes emergency surgery to evacuate a huge spinal hematoma, but his neurologic function never recovers.

Dr. Michota: I think most of us would agree that there was negligence here. I bet a plaintiff’s attorney would love to have this case.

Mr. Donnelly: Absolutely. The patient can no longer walk, so it’s already a high-value case. It would be even more so if we supposed that the patient were only 45 years old and a corporate executive. That would make it a really high-value case.

Dr. Michota: What do you mean? Does a patient’s age or economic means matter to a plaintiff’s attorney?

Mr. Donnelly: Of course. For a plaintiff’s attorney, it’s always nice to have a case like this where there’s negligence, but the high-dollar cases typically involve a likable plaintiff who is a high wage earner with a good family. A plaintiff’s lawyer will take a case that may not be so strong on evidence of negligence if it’s likely that a jury will like the plaintiff and his or her family. Kids always help to sway a jury—jurors will feel sorry for them and want to help them. This case even has two surgeries, so the family’s medical bills will be especially high. It’s a great case for a plaintiff’s attorney.

Who’s at fault?

Dr. Michota: Let’s look at a few more case details. Once the various doctors involved in this case realized what happened, they got nervous and engaged in finger-pointing. The surgeons felt that the hospitalists should have stopped the LMWH. The hospitalists claimed that since they had signed off, the surgeons should have stopped it. The physiatrist said, “Who am I to decide to stop medications? I assumed that the hospital physicians checked the medications before sending the patient to the rehab facility.”

Interestingly, a hospitalist went back and made a chart entry after the second surgery. He wrote, “Late chart entry. Discussion with surgeon regarding LMWH. I told him to stop it.” Does that make him free and clear?

Mr. Donnelly: Actually, the hospitalist just shot his credibility, and now the jury is really angry. The dollar value of the case has just gone up.

Dr. Michota: Okay, suppose the hospitalist wouldn’t do something that obvious. Instead, he goes back to the chart after the fact, finds the same color pen as the entry at the time, and writes, “Patient is okay. Please stop LMWH,” and signs his name. Is there any way anyone is going to be able to figure that out?

Mr. Donnelly: All the other doctors and nurses will testify that the note was not in the chart before. The plaintiff will hire a handwriting expert and look at the different impressions on the paper, the inks, and the style of writing. Now the hospitalist has really escalated the situation and is liable for punitive damages, which will come out of his own pocket, since malpractice insurance doesn’t cover punitive damages. His license may be threatened. The jury will really be angered, and the plaintiff’s lawyer will love stoking the situation.

If this is a typical audience of physicians involved in perioperative care, about 35% to 40% of you have been sued for malpractice and have learned the hard way some of the lessons we will discuss today. This session will begin with an overview of malpractice law and medicolegal principles, after which we will review three real-life malpractice cases and open the floor to the audience for discussion of the lessons these cases can offer.

MALPRACTICE LAWSUITS ARE COMMON, EXPENSIVE, DAMAGING

If a physician practices long enough, lawsuits are nearly inevitable, especially in certain specialties. Surgeons and anesthesiologists are sued about once every 4 to 5 years; internists generally are sued less, averaging once every 7 to 10 years,¹ but hospitalists and others who practice a good deal of perioperative care probably constitute a higher risk pool among internists.

At the same time, it is estimated that only one in eight preventable medical errors committed in hospitals results in a malpractice claim.² From 1995 to 2000, the number of new malpractice claims actually declined by approximately 4%.³

Jury awards can be huge

Fewer than half (42%) of verdicts in malpractice cases are won by plaintiffs.⁴ But when plaintiffs succeed, the awards can be costly: the mean amount of physician malpractice payments in the United States in 2006 (the most recent data available) was $311,965, according to the National Practitioner Data Bank.⁵ Cases that involve a death result in substantially higher payments, averaging $1.4 million.⁴

Lawsuits are traumatic

Even if a physician is covered by good malpractice insurance, a malpractice lawsuit typically changes his or her life. It causes major disruption to the physician’s practice and may damage his or her reputation. Lawsuits cause considerable emotional distress, including a loss of self-esteem, particularly if the physician feels that a mistake was made in the delivery of care.

CATEGORIES OF CLAIMS IN MALPRACTICE LAW

Malpractice law involves torts, which are civil wrongs causing injury to a person or property for which the plaintiff may seek redress through the courts. In general, the plaintiff seeks financial compensation. Practitioners do not go to jail for committing malpractice unless a district attorney decides that the harm was committed intentionally, in which case criminal charges may be brought.

There are many different categories of claims in malpractice law. The most common pertaining to perioperative medicine involve issues surrounding informed consent and medical negligence (the worst form being wrongful death).

Informed consent

Although everyone is familiar with informed consent, details of the process are called into question when something goes wrong. Informed consent is based on the right of patient autonomy: each person has a right to determine what will be done to his or her body, which includes the right to consent to or refuse treatment.

For any procedure, treatment, or medication, patients should be informed about the following:

• The nature of the intervention
• The benefits of the intervention (why it is being recommended)
• Significant risks reasonably expected to exist
• Available alternatives (including “no treatment”).

If possible, it is important that the patient’s family understand the risks involved, because if the patient dies or becomes incapacitated, a family that is surprised by the outcome is more likely to sue.

The standard to which physicians are held in malpractice suits is that of a “reasonable physician” dealing with a “reasonable patient.” Often, a plaintiff claims that he or she did not know that a specific risk was involved, and the doctor claims that he or she spent a “typical” amount of time explaining all the risks. If that amount of time was only a few seconds, that may not pass the “reasonable physician” test, as a jury might conclude that more time may have been necessary.

Negligence and wrongful death

Negligence, including wrongful death, is a very common category of claim. The plaintiff generally must demonstrate four elements in negligence claims:

• The provider had a duty to the patient
• The duty was breached
• An injury occurred
• The breach of duty was a “proximate cause” of the injury.

Duty arises from the physician-patient relationship: any person whose name is on the medical chart essentially has a duty to the patient and can be brought into the case, even if the involvement was only peripheral.

Breach of duty. Determining whether a breach of duty occurred often involves a battle of medical experts. The standard of care is defined as what a reasonable practitioner would do under the same or similar circumstances, assuming similar training and background. The jury decides whether the physician met the standard of care based on testimony from experts.

The Latin phrase res ipsa loquitur means “the thing speaks for itself.” In surgery, the classic example is if an instrument or a towel were accidentally left in a patient. In such a situation, the breach of duty is obvious, so the strategy of the defense generally must be to show that the patient was not harmed by the breach.

Injury. The concept of injury can be broad and often depends on distinguishing bad practice from a bad or unfortunate outcome. For instance, a patient who suffered multisystem trauma but whose life was saved by medical intervention could sue if he ended up with paresthesia in the foot afterwards. An expert may be called to help determine whether or not the complication is reasonable for the particular medical situation. Patient expectations usually factor prominently into questions of injury.

Proximate cause often enters into situations involving wrongful death. A clear understanding of the cause of death or evidence from an autopsy is not necessarily required for a plaintiff to argue that malpractice was a proximate cause of death. A plaintiff’s attorney will often speculate why a patient died, and because the plaintiff’s burden of proof is so low (see next paragraph), it may not help the defense to argue that it is pure speculation that a particular event was related to the death. 

A low burden of proof

In a civil tort, the burden of proof is established by a “preponderance of the evidence,” meaning that the allegation is “more likely than not.” This is a much lower standard than the “beyond a reasonable doubt” threshold used for criminal proceedings. In other words, the plaintiff has to show only that the chance that malpractice occurred was greater than 50%. 

Three types of damages

Potential damages (financial compensation) in malpractice suits fall into three categories:

• Economic, or the monetary costs of an injury (eg, medical bills or loss of income)
• Noneconomic (eg, pain and suffering, loss of ability to have sex)
• Punitive, or damages to punish a defendant for willful and wanton conduct.

Punitive damages are generally not covered by malpractice insurance policies and are only rarely involved in cases against an individual physician. They are more often awarded when deep pockets are perceived to be involved, such as in a case against a hospital system or an insurance company, and when the jury wants to punish the entity for doing something that was believed to be willful.

Regardless of the circumstances, communication is probably the most important factor determining whether a physician will be sued. Sometimes a doctor does everything right medically but gets sued because of lack of communication with the patient. Conversely, many of us know of veteran physicians who still practice medicine as they did 35 years ago but are never sued because they have a great rapport with their patients and their patients love them for it.

The importance of careful charting also cannot be overemphasized. In malpractice cases, experts for the plaintiff will comb through the medical records and be sure to notice if something is missing. The plaintiff also benefits enormously if, for instance, nurses documented that they paged the doctor many times over a 3-day period and got no response.

CASE 1: PATIENT DIES DURING PREOPERATIVE STRESS TEST FOR KNEE SURGERY

A 65-year-old man with New York Heart Association class III cardiac disease (marked limitation of physical activity) is scheduled for a total knee arthroplasty and is seen at the preoperative testing center. His past medical history includes coronary artery disease, chronic obstructive pulmonary disease, hypertension, and prior repair of an abdominal aortic aneurysm. He is referred for a preoperative stress test.

Dobutamine stress echocardiography is performed. His target heart rate is reached at 132 beats per minute with sporadic premature ventricular contractions. Toward the end of the test, he complains of shortness of breath and chest pain. The test is terminated, and the patient goes into ventricular tachycardia and then ventricular fibrillation. Despite resuscitative efforts, he dies.

Dr. Michota: From the family’s perspective, this patient had come for quality-of-life–enhancing surgery. They were looking forward to him getting a new knee so he could play golf again when he retired. The doctor convinced them that he needed a stress test first, which ends up killing him. Mr. Donnelly, as a lawyer, would you want to be the plaintiff’s attorney in this case?

Mr. Donnelly: Very much so. The family never contemplated that their loved one would die from this procedure. The first issue would be whether or not the possibility of complications or death from the stress test had been discussed with the patient or his family.

Consent must be truly ‘informed’ and documented

Dr. Michota: How many of our audience members who do preoperative assessments and refer patients for stress testing can recall a conversation with a patient that included the comment, “You may die from getting this test”? Before this case occurred, I never brought up this possibility, but I do now. This case illustrates how important expectations are.

Comment from the audience: I think you have to be careful of your own bias about risks. You might say to the patient, “There’s a risk that you’ll have an arrhythmia and die,” but if you also tell him, “I’ve never seen that happen during a stress test in my 10 years of practice,” you’ve biased the informed consent. The family can say, “Well, he basically told us that it wasn’t going to happen; he’d never seen a case of it.”

Dr. Michota: Are there certain things we shouldn’t say? Surely you should never promise somebody a good outcome by saying that certain rare events never happen.

Mr. Donnelly: That’s true. You can give percentages. You might say, “I’m letting you know there’s a possibility that you could die from this, but it’s a low percentage risk.” That way, you are informing the patient. This relates to the “reasonable physician” and “reasonable patient” standard. You are expected to do what is reasonable.

Is a signed consent form adequate defense?

Dr. Michota: What should the defense team do now? Let’s say informed consent was obtained and documented at the stress lab. The patient signed a form that listed death as a risk, but no family members were present. Is this an adequate defense?

Mr. Donnelly: It depends on whether the patient understood what was on the form and had the opportunity to ask questions.

Dr. Michota: So the form means nothing?

Mr. Donnelly: If he didn’t understand it, that is correct.

Dr. Michota: We thought he understood it. Can’t we just say, “Of course he understood it—he signed it.”

Mr. Donnelly: No. Keep in mind that most jurors have been patients at one time or another. There may be a perception that physicians are rushed or don’t have time to answer questions. Communication is really important here.

Dr. Michota: But surely there’s a physician on the jury who can help talk to the other jurors about how it really works.

Mr. Donnelly: No, a “jury of peers” is not a jury box of physicians. The plaintiff’s attorneys tend to exclude scientists and other educated professionals from the jury; they don’t want jurors who are accustomed to holding people to certain standards. They prefer young, impressionable people who wouldn’t think twice about awarding somebody $20 million.

Question from the audience: Who should have obtained informed consent for this patient—the doctor who referred him for the stress test or the cardiologist who conducted the test? Sometimes I have to get informed consent for specialty procedures that I myself do not understand very well. Could I be considered culpable even though I’m not the one doing the procedure? I can imagine an attorney asking, “Doctor, are you a cardiologist? How many of these tests do you do? Why are you the one doing the informed consent? Did the patient really understand the effects of the test? Do you really understand them?”

Dr. Michota: That question is even more pertinent if the patient is referred to another institution covered under different malpractice insurance. You can bet the other provider will try to blame you if something goes wrong.

Mr. Donnelly: In an ideal world, both the referring physician and the physician who does the test discuss the risks, benefits, and alternatives, and answer all questions that the patient and family have. The discussion is properly documented in the medical record.

Question from the audience: Can you address the issue of supervision? What is the liability of a resident or intern in doing the informed consent?

Mr. Donnelly: The attending physician is usually responsible for everything that a resident does. I would prefer that the attending obtain the informed consent.

Dr. Michota: But our fellows and second-year postgraduate residents are independent licensed practitioners in Ohio. Does letting them handle informed consent pose a danger to a defense team’s legal case?

Mr. Donnelly: It’s not necessarily a danger medically, but it gives the plaintiff something to talk about. They will ignore the fact that an independent licensed practitioner obtained the informed consent. They will simply focus on the fact that the physician was a resident or fellow. They will claim, “They had this young, inexperienced doctor give the informed consent when there were staff physicians with 20 years of experience who should have done it.” Plaintiffs will attempt to get a lot of mileage out of these minor issues.

Question from the audience: At our institution, the physician is present with the technician, so that when the physician obtains consent, the technician signs as a witness. The bottom of the long form basically says, “By signing this form, I attest that the physician performing the test has informed me of the benefits and risks of this test, and I agree to go ahead. I fully understand the implications of the test.” Does that have value in the eyes of the law?

Mr. Donnelly: That’s a great informed consent process and will have great value. That said, you can still get sued, because you can get sued for anything. But the jury ultimately decides, and odds are that with a process like yours they will conclude that the patient knew all the risks and benefits and alternatives because he or she signed the form and the doctor documented that everything was discussed.

Confidentiality vs family involvement

Comment from the audience: I’m struck by the comments that informed consent is supposed to be with the family so that there will be living witnesses in case the patient dies. According to Health Insurance Portability and Accountability Act (HIPAA) regulations, we have to be very careful to maintain confidentiality. For a competent patient, medical discussions are private unless specific permission has been obtained to involve the family.

Mr. Donnelly: Yes, we’ve assumed that the patient gave permission to discuss these issues with his family. If the patient does not want that, obviously you can’t include the family because of HIPAA regulations.

Question from the audience: Should we routinely ask a patient to involve the family in an informed consent in case something goes wrong?

Mr. Donnelly: No. In general, it’s appropriate only if the family is already present.

Dr. Michota: Keep in mind that there’s nothing you can do to completely prevent being sued. You can do everything right and still get sued. If you’re following good clinical practice and a patient doesn’t want to involve the family, all you can do is document your discussion and that you believed the patient understood the risks of the procedure.

Question from the audience: Do you consider a patient’s decision-making capacity for informed consent? Should physicians document it prior to obtaining consent? A plaintiff can always claim that an elderly patient did not understand.

Mr. Donnelly: I have never seen specific documentation that a patient had capacity to consent, but it’s a good idea for a borderline case. For such a case, it’s especially important to involve the family and document, “I discussed the matter with this elderly patient and her husband and three daughters.” You could also get a psychiatric consult or a social worker to help determine whether a patient has the capacity to make legal and medical decisions.

CASE 2: FATAL POSTSURGICAL MI RAISES QUESTIONS ABOUT THE PREOP EVALUATION

A 75-year-old man with rectal cancer presents for colorectal surgery. He has a remote cardiac history but exercises regularly and has a good functional classification without symptoms. The surgery is uneventful, but the patient develops hypotension in the postanesthesia care unit. He improves the next morning and goes to the colorectal surgery ward. Internal bleeding occurs but initially goes unrecognized; on postoperative day 2, his hemoglobin is found to be 2 g/dL and he is transferred to the intensive care unit, then back to the operating room, where he suffers cardiac arrest. He is revived but dies 2 weeks later. Autopsy reveals that he died of a myocardial infarction (MI).

Dr. Michota: The complaint in this case is that the patient did not receive a proper preoperative evaluation because no cardiac workup was done. As the hypothetical defense attorney, do you feel this case has merit? The patient most likely had an MI from demand ischemia due to hemorrhage, but does this have anything to do with not having a cardiac workup?

Mr. Donnelly: You as the physician are saying that even if he had an electrocardiogram (ECG), it is likely that nothing would have been determined. The cardiac problems he had prior to the surgery in question were well controlled, occurred in the distant past, and may not have affected the outcome. Maybe his remote cardiac problems were irrelevant and something else caused the MI that killed him. Nevertheless, the fact that the ECG wasn’t done still could be a major issue for the plaintiff’s attorney. After the fact, it seems like a no-brainer that an ECG should have been done in a case like this, and it’s easy for the plaintiff to argue that it might have detected something. The defense has to keep reminding the jury that the case cannot be looked at retrospectively, and that’s a tall order.

Dr. Michota: This case shows that even in the context of high-quality care, such things can happen. We have spent a lot of time at this summit talking about guidelines. But at the end of the day, if somebody dies perioperatively of an MI, the family may start looking for blame and any plaintiff’s attorney will go through the record to see if a preoperative ECG was done. If it wasn’t, a suit will get filed.

Question from the audience: Even if the physician had done the ECG, how do you know the plaintiff’s attorney wouldn’t attack him for not ordering a stress test? And if he had done a stress test, then they’d ask why he didn’t order a catheterization. Where is it going to end?

Dr. Michota: You make a good point. The best way for physicians to protect themselves is to follow the four Cs mentioned earlier: competent care, communication, compassion, and charting. After I learned about this case, the next time I was in the clinic and didn’t order an ECG, I asked the patient, “Did you expect that we would do an ECG here today?” When he responded that he did, I talked to him about how it wasn’t indicated and probably would not change management. So that level of communication can sometimes prevent a lawsuit that might stem from a patient not feeling informed. I’m not suggesting that you spend hours explaining details with each patient, but it’s good to be aware that cases like this happen and how you can reduce their likelihood.

Battles of the experts

Question from the audience: Exactly what standard is applied when the “standard of care” is determined in a court? For instance, my hospital may routinely order stress tests, whereas the American College of Cardiology and American Heart Association (ACC/AHA) guidelines are more restrictive in recommending when a stress test is indicated. Which standard would apply in court?

Dr. Michota: It’s easy to find a plaintiff’s expert who will say just about anything. If you claim that everybody gets a stress test at your community hospital and a patient dies during the stress test, the plaintiff’s team will find an expert to say, “That was an unnecessary test and posed an unnecessary risk.” If you’re in a setting where stress tests are rarely done for preoperative evaluation, they’ll find an expert to say, “Stress testing was available; it should have been done.”

This is when the battles of the experts occur. If you have a superstar physician on your defense team, the plaintiff will have to find someone of equal pedigree who can argue against him or her. Sometimes cases go away because the defense lines up amazing experts and the plaintiffs lose their stomach for the money it would take to bring the case forward. But usually cases do not involve that caliber of experts; most notables in the field are academic physicians who don’t do this type of work. Usually you get busy physicians who spend 75% of their time in clinical practice and seem smart enough to impress the jury. Although they can say things that aren’t even factual, they can sway the jury. 

Question from the audience: I would not have ordered a preoperative ECG on this healthy 75-year-old, but one of the experts at this summit said that he would get a baseline ECG for such a case. How are differences like these reconciled in the legal context?

Dr. Michota: The standard to which we are held is that of a reasonable physician. Can you show that your approach was a reasonable one? Can you say, “I didn’t order the ECG for the following reasons, and I discussed the issue with the patient”? Or alternately, “An ECG was ordered for the following reasons, and I discussed it with the patient”? The jury will want to know whether the care that was provided was reasonable.

Costs and consequences of being sued

Question from the audience: What does it cost to mount a defense in a malpractice trial?

Mr. Donnelly: You can easily spend more than $100,000 to go through a trial. Plaintiffs typically have three or four experts in various cities across the country, and you have to pay your lawyers to travel to those cities and take the depositions. And delays often occur. Cases get filed, dismissed, and refiled. A lot of the work that the lawyers did to prepare for the trial will have to be redone for a second, third, or fourth time as new dates for the trial are set. There are many unforeseen costs.

Dr. Michota: Let’s say the physician who did the preoperative evaluation in this case was not affiliated with the hospital and wasn’t involved in the surgery or any of the postoperative monitoring and management, which we see may have been questionable. This physician might get pulled into the case anyway because he didn’t order an ECG in the preoperative evaluation. Although an ECG wasn’t recommended in this case by the ACC/AHA guidelines, this doctor is looking at spending considerable time, energy, and money to defend himself. What if his attorney recommends that he settle for a nominal amount—say, $25,000—because it’s cheaper and easier? Are there repercussions for him as a physician when he pays out a settlement under his name?

Mr. Donnelly: Absolutely. He will be reported to the National Practitioner Data Bank, and when he renews his license or applies for a license to practice in another state, he must disclose that he has been sued and paid a settlement. The new consumer-targeted public reporting Web sites will also publicize this information. It is like a black mark against this doctor even though he never admitted any liability.

CASE 3: A CLEAR CASE OF NEGLIGENCE―WHO IS RESPONSIBLE

A 67-year-old man undergoes a laminectomy in the hospital. He develops shortness of breath postoperatively and is seen by the hospitalist team. He is started on full-dose weight-adjusted low-molecular-weight heparin (LMWH) for possible pulmonary embolism or acute coronary syndrome. His symptoms resolve and his workup is negative. It is a holiday weekend. The consultants sign off but do not stop the full-dose LMWH. The patient is discharged to the rehabilitation unit by the surgeon and the surgeon’s assistant, who include all the medications at discharge, including the full-dose LMWH. The patient is admitted to a subacute nursing facility, where the physiatrist transfers to the chart all the medications on which the patient was discharged.

The patient does well until postoperative day 7, when he develops urinary retention and can’t move his legs. At this point, someone finally questions why he is on the LMWH, and it is stopped. The patient undergoes emergency surgery to evacuate a huge spinal hematoma, but his neurologic function never recovers.

Dr. Michota: I think most of us would agree that there was negligence here. I bet a plaintiff’s attorney would love to have this case.

Mr. Donnelly: Absolutely. The patient can no longer walk, so it’s already a high-value case. It would be even more so if we supposed that the patient were only 45 years old and a corporate executive. That would make it a really high-value case.

Dr. Michota: What do you mean? Does a patient’s age or economic means matter to a plaintiff’s attorney?

Mr. Donnelly: Of course. For a plaintiff’s attorney, it’s always nice to have a case like this where there’s negligence, but the high-dollar cases typically involve a likable plaintiff who is a high wage earner with a good family. A plaintiff’s lawyer will take a case that may not be so strong on evidence of negligence if it’s likely that a jury will like the plaintiff and his or her family. Kids always help to sway a jury—jurors will feel sorry for them and want to help them. This case even has two surgeries, so the family’s medical bills will be especially high. It’s a great case for a plaintiff’s attorney.

Who’s at fault?

Dr. Michota: Let’s look at a few more case details. Once the various doctors involved in this case realized what happened, they got nervous and engaged in finger-pointing. The surgeons felt that the hospitalists should have stopped the LMWH. The hospitalists claimed that since they had signed off, the surgeons should have stopped it. The physiatrist said, “Who am I to decide to stop medications? I assumed that the hospital physicians checked the medications before sending the patient to the rehab facility.”

Interestingly, a hospitalist went back and made a chart entry after the second surgery. He wrote, “Late chart entry. Discussion with surgeon regarding LMWH. I told him to stop it.” Does that make him free and clear?

Mr. Donnelly: Actually, the hospitalist just shot his credibility, and now the jury is really angry. The dollar value of the case has just gone up.

Dr. Michota: Okay, suppose the hospitalist wouldn’t do something that obvious. Instead, he goes back to the chart after the fact, finds the same color pen as the entry at the time, and writes, “Patient is okay. Please stop LMWH,” and signs his name. Is there any way anyone is going to be able to figure that out?

Mr. Donnelly: All the other doctors and nurses will testify that the note was not in the chart before. The plaintiff will hire a handwriting expert and look at the different impressions on the paper, the inks, and the style of writing. Now the hospitalist has really escalated the situation and is liable for punitive damages, which will come out of his own pocket, since malpractice insurance doesn’t cover punitive damages. His license may be threatened. The jury will really be angered, and the plaintiff’s lawyer will love stoking the situation.

As a hospitalist who practices in a perioperative clinic, I probably spend more of my time with patients reviewing and discussing the medications they are taking than on any other single subject. Surgical patients—many of whom are elderly—commonly are on multiple medications, have renal or hepatic disease that can alter drug metabolism, and may not be adequately educated about their medication regimens.

Patient safety is the overriding concern behind perioperative medication management, consistent with the medication-related objectives in the Joint Commission’s 2009 National Patient Safety Goals.¹ The increasing surgical burden that comes with an aging population, along with rising expectations for functional recovery, has likewise elevated the importance of perioperative medication management.

Despite these demands, there is scant evidence from randomized controlled trials to directly guide perioperative medication management. For this reason, recommendations in this area rely largely on other forms of evidence, including expert consensus, case reports, in vitro studies, recommendations from pharmaceutical companies, and other known data (pharmacokinetics, drug interactions with anesthetic agents, and effects of the agent on the primary disease and on perioperative risk).

This article reviews general principles of perioperative medication management and then presents four case vignettes to explore perioperative recommendations for a number of common medication classes. It is not intended as a comprehensive review of the perioperative management of all medications, as numerous classes (antiplatelets, beta-blockers, oral hypogycemic agents, insulin, statins) are discussed in detail elsewhere in this proceedings supplement.

GENERAL CONSIDERATIONS IN MEDICATION MANAGEMENT

A comprehensive medication history is fundamental

Effective perioperative management of medications requires an understanding of the patient and his or her comorbidities so that the risk of perioperative decompensation can be gauged. This understanding stems from a thorough medical history that includes a comprehensive medication history to provide a complete inventory of the following:

• All prescription medications
• All over-the-counter (OTC) agents (including nonsteroidal anti-inflammatory drugs [NSAIDs])
• All vitamins
• All herbal medications.

When to stop, when to resume?

Guidance on stopping and resuming medications in the perioperative period is relatively absent from the literature. General considerations include the following:

• The potential for withdrawal when stopping a medication
• The progression of disease with interruption of drug therapy
• The potential for interactions with anesthetic agents if the medication is continued.

Withdrawal potential

Abrupt discontinuation of some drugs may lead to unnecessary complications due to the potential for withdrawal. Common medications that have been associated with withdrawal symptoms are selective serotonin reuptake inhibitors (SSRIs), beta-blockers, clonidine, statins, and corticosteroids.² A recent systematic literature review concluded that continuation of chronic corticosteroid therapy without supplemental (stress) doses of corticosteroids is appropriate unless patients have primary disease of the hypothalamic-pituitary-adrenal axis, in which case perioperative stress dosing is recommended to avoid acute adrenal insufficiency (addisonian crisis).³

Patients on chronic drugs are more likely to have complications

In a medication survey of 1,025 patients admitted to a general surgery unit, Kennedy et al reported that 49% of the patients were taking medications (other than vitamins) unrelated to their surgical procedure.⁴ Even while this percentage is considerably lower than what I observe in my practice, this study showed that medication use has important perioperative consequences⁴:

• The odds ratio for a postoperative complication was 2.7 (95% CI, 1.76–4.04) if patients were taking a drug unrelated to their surgery.
• The risk of a complication was particularly elevated if patients were taking cardiovascular drugs or agents that act on the central nervous system; if patients were on NPO (“nothing by mouth”) orders for more than 24 hours before surgery; and if the operation was more than 1 hour in duration. These findings could reflect destabilization of the disease processes for which the patients were taking chronic medications that required interruption.

Unintended discontinuation of chronic drugs

Stopping a chronic medication for a surgical procedure raises the possibility that its resumption could be overlooked, especially since medical errors are particularly common in the transition between health care settings following hospital discharge. A population-based cohort study among all elderly patients discharged from Ontario, Canada, hospitals over a 5½-year period found that 11.4% of patients undergoing elective surgery did not resume their indicated chronic warfarin therapy within 6 months after its presurgical discontinuation.⁵ Although 6-month rates of unintended failure to resume therapy were lower for statins (4%) and ophthalmic beta-blocker drops (8%),⁵ these findings underscore that drug discontinuation always carries a risk that therapy might not be resumed as indicated.

Additional considerations

Stress response to surgery. Decisions about perioperative drug therapy should always take into account the stress response to surgery and the challenge it presents to homeostasis in the face of increased sympathetic tone and release of pituitary hormones.

Unreliable absorption of oral medications. Surgery and the postoperative state can lead to unreliable absorption of oral drugs for any of a number of reasons: villous atrophy, diminished blood flow to the gut, edema, mucosal ischemia, diminished motility from postoperative ileus, and use of narcotics.⁶

Take-away general principles

The following principles can be applied to guide peri­operative medication management in a general sense⁷:

• Continue medications with withdrawal potential
• Discontinue medications that increase surgical risk and are not essential for short-term quality of life
• Use clinical judgment when neither of the above two principles applies, but be mindful that many other medications are given in the narrow perioperative time window and that metabolism and elimination of chronic drugs may be altered.

A 55-year-old man with severe osteoarthritis is scheduled for total hip arthroplasy in 2 days. He stopped his aspirin (325 mg/day) 1 week ago but continued taking ibuprofen 600 three times daily with food, explaining that “no one told me to stop.” His last dose was yesterday evening.

Question: What should you do?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop the ibuprofen now

C. Check his bleeding time and proceed if normal

D. Just tell the patient to stop the ibuprofen now

E. Proceed to the operating room regardless of the ibuprofen dose

The best approach would be to notify the surgeon and tell the patient to stop the ibuprofen now. NSAIDs such as ibuprofen reversibly inhibit platelet cyclooxygenase (COX), diminish thromboxane A₂ production, diminish platelet aggregation, and can increase bleeding time measurement and overall bleeding risk. They can induce renal failure in combination with other drugs, especially in the setting of hypotension.^8,9 COX-2 inhibitors have less effect on platelet function but retain the potential for renal toxicity and also confer well-known cardio­vascular risks.

In the past, NSAIDs were typically held for 7 days before surgery, but this practice was not supported with much evidence. In vitro assessment indicates that platelet function normalizes within 24 hours after cessation of regular ibuprofen or dexibuprofen in healthy individuals.^10,11

Since NSAIDs vary in their effect on bleeding time, which does not correlate well with elimination half-life, a general recommendation is to stop most NSAIDs at least 3 days before surgery.

CASE 2: A PATIENT ON MULTIPLE CARDIOVASCULAR DRUGS

A 67-year-old man with dilated cardiomyopathy and an ejection fraction of 25% (well compensated) is scheduled for a laparoscopic cholecystectomy tomorrow. He is taking lisinopril (40 mg/day), irbesartan (150 mg/day), and furosemide (80 mg/day).

Question: What is your advice?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop his medications now

C. Hold all of the above medications on the morning of surgery

D. Proceed to the operating room with the usual doses of his medications on the morning of surgery

The best approach is to withhold these medications on the morning of surgery.

Diuretics are typically held on the morning of surgery because of the potential for hypovolemia and electrolyte depletion.

Angiotensin-converting enzyme (ACE) inhibitors intensify the hypotensive effects of anesthesia induction. Because angiotensin II plays a key role in maintaining circulating volume in response to stressors, volume deficits can occur in ACE inhibitor-treated patients as angiotensin II cannot compensate for venous pooling of blood, resulting in diminished cardiac output and arterial hypotension. However, continued renin-angiotensin system suppression may protect regional circulation, as has been demonstrated by reduced release of cardiac enzymes with ACE inhibitor continuation (compared with interruption) in cardiac surgery patients. ACE inhibitors also have a renal protective effect, preserving glomerular filtration rate in patients undergoing aortic abdominal aneurysm repair or coronary artery bypass graft surgery. Hypotension with ACE inhibition is treatable with sympathomimetics, alpha-agonists, and intravenous fluids.^12–15

If a patient’s ACE inhibitor is stopped, be prepared for rebound postoperative hypertension. The probability of postoperative atrial fibrillation is also increased with ACE inhibitor interruption.¹⁴ In patients with left ventricular dysfunction undergoing noncardiac vascular surgery, continued ACE inhibition is associated with reduced mortality.¹⁶ These data argue, at the very least, for prompt resumption of ACE inhibitors after surgery.

Angiotensin receptor blockers (ARBs) have largely the same clinical benefits as do ACE inhibitors. These agents also increase the risk of hypotension upon induction of anesthesia, and this hypotension is not as responsive to conventional vasopressors such as ephedrine and phenylephrine; a better response is achieved with vasopressin.¹⁵ In light of the long half-life of ARBs, current thinking is to withhold them 24 hours before surgery.

Rosenman et al recently published a meta-analysis of five studies assessing the effects of continuing or withholding ACE inhibitors and ARBs in the preoperative period.¹⁷ They found a statistically significant increase in the incidence of perioperative hypotension in patients in whom the drugs were continued compared with those in whom the drugs were withheld (relative risk = 1.50; 95% CI, 1.15–1.96), but there was no significant difference in the rate of perioperative MI between the two groups. Notably, the indication for ACE inhibitor or ARB use in all of the studies was hypertension, not heart failure.

My approach to the perioperative management of ACE inhibitors and ARBs is to withhold them on the morning of surgery (in the case of ARBs, 24 hours prior to surgery) if their only indication is for hypertension and if the patient’s blood pressure is well controlled. If the patient has another indication for these agents or has hypertension that is not well controlled, I am inclined to continue these agents but will first discuss the decision with the anesthesiologist.

A 68-year-old woman with a history of hypertension, osteoarthritis, and osteoporosis is scheduled for total hip replacement in 7 days. Her medications include atenolol, hydrochlorothiazide, and alendronate. She also reports taking some natural herbal medications. She does not recall their names initially but calls back with the names: ginkgo biloba for her memory and echinacea for her immune system.

Question: What are your recommendations?

A. Stop all medications now except atenolol and proceed to surgery

B. Stop the herbals now but take all other medications on the morning of surgery

C. Stop the herbals now and take only atenolol on the morning of surgery

D. Continue all medications now and take atenolol and the herbals on the morning of surgery

E. Cancel the surgery and call an herbalist for guidance

The best strategy is to stop the herbals now and tell her to take only atenolol (a beta-blocker) on the morning of surgery.

Because the US Food and Drug Administration (FDA) does not regulate herbal products, the contents of these products can vary widely. For example, an analysis using mass spectrometry of 50 commercial ginseng products from 11 countries found that the ginseng content varied from 0% (six preparations) to 9%.¹⁹ Catecholamine-type compounds were found in some of the products.¹⁹

Because of the uncertainty over their actual contents, herbal medications should be stopped at least 7 days prior to surgery. If a patient is still taking herbal supplements on the day before surgery, I typically alert the anesthesiologist and surgeon.

CASE 4: A PATIENT ON MULTIPLE PSYCHOTROPICS

A 38-year-old woman with a history of severe major depression is scheduled for a mastectomy for breast cancer the next day. Her medications include fluoxetine, lorazepam, and phenelzine, all of which she has been taking for many years.

Question: What is your course of action?

A. Call the surgeon and cancel the surgery

B. Call the surgeon and notify the day-of-surgery anesthesiologist that the patient is taking these agents

C. Stop all the medications now and proceed to the operating room

D. Request a psychiatric consult for an alternative drug regimen

E. Proceed and advise the patient to take all of these agents on the morning of surgery

My approach would be to notify the day-of-surgery anesthesiologist, specifically about the phenelzine, which is a monoamine oxidase (MAO) inhibitor (see below). The other two agents can be taken on the morning of surgery, although fluoxetine has a long half-life, so missing a dose should not be problematic, and lorazepam can be given intravenously if needed.

SSRIs, including fluoxetine, are generally safe peri­operatively. Serotonin depletion from platelets, however, increases the risk of bleeding, especially gastrointestinal bleeding, when SSRIs are used with NSAIDs.^20–22 A neurosurgical procedure may therefore be especially risky in patients who have not stopped their SSRI if they are also taking an NSAID or an herbal medication that may increase the risk of bleeding. The caveat to stopping SSRIs is the potential for a minor withdrawal syndrome.

Tricyclic antidepressants inhibit the reuptake of norepinephrine and serotonin and may increase the action of sympathomimetics. Although arrhythmias are thought to be a concern with tricyclics, there are no reported cases of association in the literature. In general, I advise continuing triclyclics perioperatively, especially in patients who are on high doses.

Benzodiazepines, including lorazepam, are safe to use perioperatively, and a potential for withdrawal symptoms (hypertension, agitation, delirium, seizures) argues against their discontinuation. Chronic benzodiazepine use may increase anesthetic requirements.

Antipsychotic agents, which include haloperidol, olanzapine, risperidone, and ziprasidone, have multiple routes of administration—intramuscular, oral, sublingual, and intravenous. These agents are generally safe to use in the perioperative period.

MAO inhibitors, including phenelzine, are no longer commonly used and are typically reserved for the treatment of refractory depression. But they merit attention, as their use can cause accumulation of biogenic amines in the central and autonomic nervous systems. There are two types of MAO reactions—excitatory and depressive. Excitatory reactions lead to serotonin syndrome. Depressive reactions induce inhibition of hepatic microsomal enzymes, leading to narcotic accumulation and increased sedation.²³

MAO inhibitors are also of concern because of their many drug interactions. When used with indirect sympathomimetics such as ephedrine, they promote a massive release of stored norepinephrine, leading to severe hypertension. When used with opioids like meperidine and dextromethorphan, MAO inhibitors are associated with a serotonin syndrome characterized by agitation, headache, fever, seizures, coma, and death.

Discontinuing MAO inhibitors before the day of surgery is no longer universally recommended, due to the risk of precipitating an exacerbation of major depression. Safe anesthetic regimens in the setting of MAO inhibitors involve avoidance of meperidine (morphine and fentanyl are safe) and use of only direct-acting sympathomimetics.

A good medication history that includes herbal and OTC products is essential for safe induction of anesthesia and optimization of outcomes during and following surgery. In general, medications with the potential to induce withdrawal symptoms should be continued. The use of nonessential medications that can increase surgical risk should be discontinued. If neither of these conditions applies, consider the patient’s risk profile and the risk of the procedure when making perioperative management decisions. Be mindful of withdrawal syndromes and resume medications with the potential for such syndromes as soon as possible.

DISCUSSION

Comment from the audience: In regard to your comment that diuretics are typically held on the morning of surgery, my institution recently completed a randomized placebo-controlled trial (publication is pending) in which we studied the effect of continuing or not continuing furosemide preoperatively. We found no difference in the occurrence of intraoperative hypotension between the two groups. It will be interesting to see if these findings change practice over time.

Dr. Whinney: It’s good to know that hypotension is not a concern with furosemide, but the issue here is not just blood pressure but electrolyte abnormalities that could predispose to arrhythmias. The patients who concern me are those who haven’t been seen by a physician for a while and may be on high doses of furosemide. I would scrutinize such patients closely.

Question from the audience: We see a number of patients on methotrexate and other disease-modifying rheumatologic drugs. Can you comment on the peri­operative management of these medications?

Dr. Whinney: Methotrexate has caused some anxiety over the risk of infection, but the literature does not support such concern.²⁴ In fact, it appears that continuing methotrexate is probably advisable because the risk of decompensation of the disease may be worse than the potential infectious risks. The only caveat is the patient with renal insufficiency, in whom the recommendation is to withhold methotrexate for 2 weeks before surgery. While most rheumatologists favor withholding disease-modifying drugs perioperatively, a recent systematic review showed no increased risk of either total or infectious complications with use of immunomodulators including infliximab, azathioprine, and cyclosporine.²⁵ It is still reasonable and prudent to discuss this issue with the patient’s rheumatologist. Hydroxychloroquine is safe to continue.

Comment from the audience: First, I would like to urge everyone to be mindful of medication-related indications for preoperative testing. There are many psychotropic drugs that prolong the QT interval and thus constitute an indication for a baseline electrocardiogram prior to surgery. Second, I believe there is a mythology in the perioperative community about the bleeding risk associated with omega-3 fatty acids and vitamin E. Can you comment on the bleeding risks associated with each?

Dr. Whinney: There are few data; the fear is based purely on the potential of these compounds to cause bleeding. Neither is beneficial for short-term quality of life or for chronic prevention, and there’s no withdrawal syndrome from either. So I generally withhold them, but if the patient is still taking them up to the day of surgery, it doesn’t merit postponing surgery. I generally let the surgeon or the nurse know, and it tends not to be a big deal.

Question from the audience: Do you stop herbal teas, energy drinks, and diet medications such as phentermine prior to surgery?

Dr. Whinney: You need to know which diet medications the patient is taking. The problem with many of the OTC products is that they may or may not be considered drugs, so they may not be approved by the FDA and thus you don’t know what the patient is actually taking. For the most part, a diet medication does not contribute to short-term quality of life. My aim is to get the patient through surgery as safely as possible, so if a patient is taking an agent with ingredients, known or unknown, with an interaction potential, then I will stop it.

The two types of diet agents are those that block the absorption of fat, which could interact with other oral agents given at the same time, and those that act via the gastrointestinal tract. I generally withhold the fat-absorption blockers the day before surgery. Phentermine has the potential for catecholinergic reactions or sympathomimetic actions. I would put it in the category of herbal-type medicines and withhold it for at least 7 days.

Question from the audience: Can you comment on combination drugs such as losartan/hydrochlorothiazide on the morning of surgery?

Dr. Whinney: The ARB losartan may have more physiologic benefit than the diuretic, so I would prescribe a single dose of losartan the morning of surgery if I had decided to continue this class of medication for uncontrolled hypertension or concern over heart failure decompensation. The same is true for a beta-blocker/diuretic combination product; I will prescribe the beta-blocker component individually and tell the patient to take it the morning of surgery.

Question from the audience: I’m confused by the recommendation to stop hydrochlorothiazide. It’s a far less potent diuretic than furosemide. Does the risk of stopping it, with resulting blood pressure elevation, outweigh the risk of a mild hypotensive response because of a mild diuretic effect? I’m aware of no data on the risk of stopping hydrochlorothiazide—are you?

Dr. Whinney: There are no data. Again, the recommendation is based on the physiology of the drug, as well as on expert consensus and opinion. Since anesthesia has a vasodilatory effect with a hypotensive response, it’s probably reasonable to hold hydrochlorothiazide if its only indication is for hypertension. That’s the logic behind the recommendation. If you continue it the day of surgery, it may not necessarily hurt, but we’re not certain.

Question from the audience: The implication from your third case study was that alendronate should be held. What’s the basis of that recommendation?

Dr. Whinney: First, the patient has to be upright for 30 minutes after taking alendronate, which could be a problem on the morning of surgery. Also, withholding it will not impair short-term quality of life; it’s a weekly medication, so the patient can take her next dose once she’s up and ambulatory.

Question from the audience: What do you for young women on oral contraceptives? I’m lucky if I see them within 7 days of surgery.

Dr. Whinney: You’re bringing up the concern with exogenous hormones and the risk of venous thrombo­embolism (VTE), a risk that clearly is increased with the hypercoagulable milieu of surgery. The recommendation is to stop hormone therapy 30 to 45 days prior to surgery in these patients. As you note, however, we don’t get the chance to see patients during that window of opportunity. So the question is whether stopping hormones within a shorter time period results in an incremental benefit. And that is not necessarily the case. These patients should be seen as being at risk for VTE and be given appropriate VTE prophylaxis. In fact, in the similar context of menopausal hormone therapy, a study among women undergoing orthopedic surgery showed that as long as they received appropriate VTE prophylaxis, there was no significant difference in VTE rates between the women whose hormone therapy was withheld versus those who continued it.²⁶

Question from the audience: Are there concerns about withdrawal in patients with peripheral vascular disease treated with cilostazol or pentoxifylline?

Dr. Whinney: It’s not particularly well studied. Guidelines from the American College of Physicians suggest to hold these agents for elective surgeries.²⁷ With respect to antiplatelet therapies, O’Riordan et al did a systematic review of 99 articles pertaining to antiplatelet agents in the perioperative period and concluded that aspirin should not be stopped in patients going for surgery.²⁸ In vascular surgery, antiplatelet agents may help promote graft patency.

As a hospitalist who practices in a perioperative clinic, I probably spend more of my time with patients reviewing and discussing the medications they are taking than on any other single subject. Surgical patients—many of whom are elderly—commonly are on multiple medications, have renal or hepatic disease that can alter drug metabolism, and may not be adequately educated about their medication regimens.

Patient safety is the overriding concern behind perioperative medication management, consistent with the medication-related objectives in the Joint Commission’s 2009 National Patient Safety Goals.¹ The increasing surgical burden that comes with an aging population, along with rising expectations for functional recovery, has likewise elevated the importance of perioperative medication management.

Despite these demands, there is scant evidence from randomized controlled trials to directly guide perioperative medication management. For this reason, recommendations in this area rely largely on other forms of evidence, including expert consensus, case reports, in vitro studies, recommendations from pharmaceutical companies, and other known data (pharmacokinetics, drug interactions with anesthetic agents, and effects of the agent on the primary disease and on perioperative risk).

This article reviews general principles of perioperative medication management and then presents four case vignettes to explore perioperative recommendations for a number of common medication classes. It is not intended as a comprehensive review of the perioperative management of all medications, as numerous classes (antiplatelets, beta-blockers, oral hypogycemic agents, insulin, statins) are discussed in detail elsewhere in this proceedings supplement.

GENERAL CONSIDERATIONS IN MEDICATION MANAGEMENT

A comprehensive medication history is fundamental

Effective perioperative management of medications requires an understanding of the patient and his or her comorbidities so that the risk of perioperative decompensation can be gauged. This understanding stems from a thorough medical history that includes a comprehensive medication history to provide a complete inventory of the following:

• All prescription medications
• All over-the-counter (OTC) agents (including nonsteroidal anti-inflammatory drugs [NSAIDs])
• All vitamins
• All herbal medications.

When to stop, when to resume?

Guidance on stopping and resuming medications in the perioperative period is relatively absent from the literature. General considerations include the following:

• The potential for withdrawal when stopping a medication
• The progression of disease with interruption of drug therapy
• The potential for interactions with anesthetic agents if the medication is continued.

Withdrawal potential

Abrupt discontinuation of some drugs may lead to unnecessary complications due to the potential for withdrawal. Common medications that have been associated with withdrawal symptoms are selective serotonin reuptake inhibitors (SSRIs), beta-blockers, clonidine, statins, and corticosteroids.² A recent systematic literature review concluded that continuation of chronic corticosteroid therapy without supplemental (stress) doses of corticosteroids is appropriate unless patients have primary disease of the hypothalamic-pituitary-adrenal axis, in which case perioperative stress dosing is recommended to avoid acute adrenal insufficiency (addisonian crisis).³

Patients on chronic drugs are more likely to have complications

In a medication survey of 1,025 patients admitted to a general surgery unit, Kennedy et al reported that 49% of the patients were taking medications (other than vitamins) unrelated to their surgical procedure.⁴ Even while this percentage is considerably lower than what I observe in my practice, this study showed that medication use has important perioperative consequences⁴:

• The odds ratio for a postoperative complication was 2.7 (95% CI, 1.76–4.04) if patients were taking a drug unrelated to their surgery.
• The risk of a complication was particularly elevated if patients were taking cardiovascular drugs or agents that act on the central nervous system; if patients were on NPO (“nothing by mouth”) orders for more than 24 hours before surgery; and if the operation was more than 1 hour in duration. These findings could reflect destabilization of the disease processes for which the patients were taking chronic medications that required interruption.

Unintended discontinuation of chronic drugs

Stopping a chronic medication for a surgical procedure raises the possibility that its resumption could be overlooked, especially since medical errors are particularly common in the transition between health care settings following hospital discharge. A population-based cohort study among all elderly patients discharged from Ontario, Canada, hospitals over a 5½-year period found that 11.4% of patients undergoing elective surgery did not resume their indicated chronic warfarin therapy within 6 months after its presurgical discontinuation.⁵ Although 6-month rates of unintended failure to resume therapy were lower for statins (4%) and ophthalmic beta-blocker drops (8%),⁵ these findings underscore that drug discontinuation always carries a risk that therapy might not be resumed as indicated.

Additional considerations

Stress response to surgery. Decisions about perioperative drug therapy should always take into account the stress response to surgery and the challenge it presents to homeostasis in the face of increased sympathetic tone and release of pituitary hormones.

Unreliable absorption of oral medications. Surgery and the postoperative state can lead to unreliable absorption of oral drugs for any of a number of reasons: villous atrophy, diminished blood flow to the gut, edema, mucosal ischemia, diminished motility from postoperative ileus, and use of narcotics.⁶

Take-away general principles

The following principles can be applied to guide peri­operative medication management in a general sense⁷:

• Continue medications with withdrawal potential
• Discontinue medications that increase surgical risk and are not essential for short-term quality of life
• Use clinical judgment when neither of the above two principles applies, but be mindful that many other medications are given in the narrow perioperative time window and that metabolism and elimination of chronic drugs may be altered.

A 55-year-old man with severe osteoarthritis is scheduled for total hip arthroplasy in 2 days. He stopped his aspirin (325 mg/day) 1 week ago but continued taking ibuprofen 600 three times daily with food, explaining that “no one told me to stop.” His last dose was yesterday evening.

Question: What should you do?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop the ibuprofen now

C. Check his bleeding time and proceed if normal

D. Just tell the patient to stop the ibuprofen now

E. Proceed to the operating room regardless of the ibuprofen dose

The best approach would be to notify the surgeon and tell the patient to stop the ibuprofen now. NSAIDs such as ibuprofen reversibly inhibit platelet cyclooxygenase (COX), diminish thromboxane A₂ production, diminish platelet aggregation, and can increase bleeding time measurement and overall bleeding risk. They can induce renal failure in combination with other drugs, especially in the setting of hypotension.^8,9 COX-2 inhibitors have less effect on platelet function but retain the potential for renal toxicity and also confer well-known cardio­vascular risks.

In the past, NSAIDs were typically held for 7 days before surgery, but this practice was not supported with much evidence. In vitro assessment indicates that platelet function normalizes within 24 hours after cessation of regular ibuprofen or dexibuprofen in healthy individuals.^10,11

Since NSAIDs vary in their effect on bleeding time, which does not correlate well with elimination half-life, a general recommendation is to stop most NSAIDs at least 3 days before surgery.

CASE 2: A PATIENT ON MULTIPLE CARDIOVASCULAR DRUGS

A 67-year-old man with dilated cardiomyopathy and an ejection fraction of 25% (well compensated) is scheduled for a laparoscopic cholecystectomy tomorrow. He is taking lisinopril (40 mg/day), irbesartan (150 mg/day), and furosemide (80 mg/day).

Question: What is your advice?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop his medications now

C. Hold all of the above medications on the morning of surgery

D. Proceed to the operating room with the usual doses of his medications on the morning of surgery

The best approach is to withhold these medications on the morning of surgery.

Diuretics are typically held on the morning of surgery because of the potential for hypovolemia and electrolyte depletion.

Angiotensin-converting enzyme (ACE) inhibitors intensify the hypotensive effects of anesthesia induction. Because angiotensin II plays a key role in maintaining circulating volume in response to stressors, volume deficits can occur in ACE inhibitor-treated patients as angiotensin II cannot compensate for venous pooling of blood, resulting in diminished cardiac output and arterial hypotension. However, continued renin-angiotensin system suppression may protect regional circulation, as has been demonstrated by reduced release of cardiac enzymes with ACE inhibitor continuation (compared with interruption) in cardiac surgery patients. ACE inhibitors also have a renal protective effect, preserving glomerular filtration rate in patients undergoing aortic abdominal aneurysm repair or coronary artery bypass graft surgery. Hypotension with ACE inhibition is treatable with sympathomimetics, alpha-agonists, and intravenous fluids.^12–15

If a patient’s ACE inhibitor is stopped, be prepared for rebound postoperative hypertension. The probability of postoperative atrial fibrillation is also increased with ACE inhibitor interruption.¹⁴ In patients with left ventricular dysfunction undergoing noncardiac vascular surgery, continued ACE inhibition is associated with reduced mortality.¹⁶ These data argue, at the very least, for prompt resumption of ACE inhibitors after surgery.

Angiotensin receptor blockers (ARBs) have largely the same clinical benefits as do ACE inhibitors. These agents also increase the risk of hypotension upon induction of anesthesia, and this hypotension is not as responsive to conventional vasopressors such as ephedrine and phenylephrine; a better response is achieved with vasopressin.¹⁵ In light of the long half-life of ARBs, current thinking is to withhold them 24 hours before surgery.

Rosenman et al recently published a meta-analysis of five studies assessing the effects of continuing or withholding ACE inhibitors and ARBs in the preoperative period.¹⁷ They found a statistically significant increase in the incidence of perioperative hypotension in patients in whom the drugs were continued compared with those in whom the drugs were withheld (relative risk = 1.50; 95% CI, 1.15–1.96), but there was no significant difference in the rate of perioperative MI between the two groups. Notably, the indication for ACE inhibitor or ARB use in all of the studies was hypertension, not heart failure.

My approach to the perioperative management of ACE inhibitors and ARBs is to withhold them on the morning of surgery (in the case of ARBs, 24 hours prior to surgery) if their only indication is for hypertension and if the patient’s blood pressure is well controlled. If the patient has another indication for these agents or has hypertension that is not well controlled, I am inclined to continue these agents but will first discuss the decision with the anesthesiologist.

A 68-year-old woman with a history of hypertension, osteoarthritis, and osteoporosis is scheduled for total hip replacement in 7 days. Her medications include atenolol, hydrochlorothiazide, and alendronate. She also reports taking some natural herbal medications. She does not recall their names initially but calls back with the names: ginkgo biloba for her memory and echinacea for her immune system.

Question: What are your recommendations?

A. Stop all medications now except atenolol and proceed to surgery

B. Stop the herbals now but take all other medications on the morning of surgery

C. Stop the herbals now and take only atenolol on the morning of surgery

D. Continue all medications now and take atenolol and the herbals on the morning of surgery

E. Cancel the surgery and call an herbalist for guidance

The best strategy is to stop the herbals now and tell her to take only atenolol (a beta-blocker) on the morning of surgery.

Because the US Food and Drug Administration (FDA) does not regulate herbal products, the contents of these products can vary widely. For example, an analysis using mass spectrometry of 50 commercial ginseng products from 11 countries found that the ginseng content varied from 0% (six preparations) to 9%.¹⁹ Catecholamine-type compounds were found in some of the products.¹⁹

Because of the uncertainty over their actual contents, herbal medications should be stopped at least 7 days prior to surgery. If a patient is still taking herbal supplements on the day before surgery, I typically alert the anesthesiologist and surgeon.

CASE 4: A PATIENT ON MULTIPLE PSYCHOTROPICS

A 38-year-old woman with a history of severe major depression is scheduled for a mastectomy for breast cancer the next day. Her medications include fluoxetine, lorazepam, and phenelzine, all of which she has been taking for many years.

Question: What is your course of action?

A. Call the surgeon and cancel the surgery

B. Call the surgeon and notify the day-of-surgery anesthesiologist that the patient is taking these agents

C. Stop all the medications now and proceed to the operating room

D. Request a psychiatric consult for an alternative drug regimen

E. Proceed and advise the patient to take all of these agents on the morning of surgery

My approach would be to notify the day-of-surgery anesthesiologist, specifically about the phenelzine, which is a monoamine oxidase (MAO) inhibitor (see below). The other two agents can be taken on the morning of surgery, although fluoxetine has a long half-life, so missing a dose should not be problematic, and lorazepam can be given intravenously if needed.

SSRIs, including fluoxetine, are generally safe peri­operatively. Serotonin depletion from platelets, however, increases the risk of bleeding, especially gastrointestinal bleeding, when SSRIs are used with NSAIDs.^20–22 A neurosurgical procedure may therefore be especially risky in patients who have not stopped their SSRI if they are also taking an NSAID or an herbal medication that may increase the risk of bleeding. The caveat to stopping SSRIs is the potential for a minor withdrawal syndrome.

Tricyclic antidepressants inhibit the reuptake of norepinephrine and serotonin and may increase the action of sympathomimetics. Although arrhythmias are thought to be a concern with tricyclics, there are no reported cases of association in the literature. In general, I advise continuing triclyclics perioperatively, especially in patients who are on high doses.

Benzodiazepines, including lorazepam, are safe to use perioperatively, and a potential for withdrawal symptoms (hypertension, agitation, delirium, seizures) argues against their discontinuation. Chronic benzodiazepine use may increase anesthetic requirements.

Antipsychotic agents, which include haloperidol, olanzapine, risperidone, and ziprasidone, have multiple routes of administration—intramuscular, oral, sublingual, and intravenous. These agents are generally safe to use in the perioperative period.

MAO inhibitors, including phenelzine, are no longer commonly used and are typically reserved for the treatment of refractory depression. But they merit attention, as their use can cause accumulation of biogenic amines in the central and autonomic nervous systems. There are two types of MAO reactions—excitatory and depressive. Excitatory reactions lead to serotonin syndrome. Depressive reactions induce inhibition of hepatic microsomal enzymes, leading to narcotic accumulation and increased sedation.²³

MAO inhibitors are also of concern because of their many drug interactions. When used with indirect sympathomimetics such as ephedrine, they promote a massive release of stored norepinephrine, leading to severe hypertension. When used with opioids like meperidine and dextromethorphan, MAO inhibitors are associated with a serotonin syndrome characterized by agitation, headache, fever, seizures, coma, and death.

Discontinuing MAO inhibitors before the day of surgery is no longer universally recommended, due to the risk of precipitating an exacerbation of major depression. Safe anesthetic regimens in the setting of MAO inhibitors involve avoidance of meperidine (morphine and fentanyl are safe) and use of only direct-acting sympathomimetics.

A good medication history that includes herbal and OTC products is essential for safe induction of anesthesia and optimization of outcomes during and following surgery. In general, medications with the potential to induce withdrawal symptoms should be continued. The use of nonessential medications that can increase surgical risk should be discontinued. If neither of these conditions applies, consider the patient’s risk profile and the risk of the procedure when making perioperative management decisions. Be mindful of withdrawal syndromes and resume medications with the potential for such syndromes as soon as possible.

DISCUSSION

Comment from the audience: In regard to your comment that diuretics are typically held on the morning of surgery, my institution recently completed a randomized placebo-controlled trial (publication is pending) in which we studied the effect of continuing or not continuing furosemide preoperatively. We found no difference in the occurrence of intraoperative hypotension between the two groups. It will be interesting to see if these findings change practice over time.

Dr. Whinney: It’s good to know that hypotension is not a concern with furosemide, but the issue here is not just blood pressure but electrolyte abnormalities that could predispose to arrhythmias. The patients who concern me are those who haven’t been seen by a physician for a while and may be on high doses of furosemide. I would scrutinize such patients closely.

Question from the audience: We see a number of patients on methotrexate and other disease-modifying rheumatologic drugs. Can you comment on the peri­operative management of these medications?

Dr. Whinney: Methotrexate has caused some anxiety over the risk of infection, but the literature does not support such concern.²⁴ In fact, it appears that continuing methotrexate is probably advisable because the risk of decompensation of the disease may be worse than the potential infectious risks. The only caveat is the patient with renal insufficiency, in whom the recommendation is to withhold methotrexate for 2 weeks before surgery. While most rheumatologists favor withholding disease-modifying drugs perioperatively, a recent systematic review showed no increased risk of either total or infectious complications with use of immunomodulators including infliximab, azathioprine, and cyclosporine.²⁵ It is still reasonable and prudent to discuss this issue with the patient’s rheumatologist. Hydroxychloroquine is safe to continue.

Comment from the audience: First, I would like to urge everyone to be mindful of medication-related indications for preoperative testing. There are many psychotropic drugs that prolong the QT interval and thus constitute an indication for a baseline electrocardiogram prior to surgery. Second, I believe there is a mythology in the perioperative community about the bleeding risk associated with omega-3 fatty acids and vitamin E. Can you comment on the bleeding risks associated with each?

Dr. Whinney: There are few data; the fear is based purely on the potential of these compounds to cause bleeding. Neither is beneficial for short-term quality of life or for chronic prevention, and there’s no withdrawal syndrome from either. So I generally withhold them, but if the patient is still taking them up to the day of surgery, it doesn’t merit postponing surgery. I generally let the surgeon or the nurse know, and it tends not to be a big deal.

Question from the audience: Do you stop herbal teas, energy drinks, and diet medications such as phentermine prior to surgery?

Dr. Whinney: You need to know which diet medications the patient is taking. The problem with many of the OTC products is that they may or may not be considered drugs, so they may not be approved by the FDA and thus you don’t know what the patient is actually taking. For the most part, a diet medication does not contribute to short-term quality of life. My aim is to get the patient through surgery as safely as possible, so if a patient is taking an agent with ingredients, known or unknown, with an interaction potential, then I will stop it.

The two types of diet agents are those that block the absorption of fat, which could interact with other oral agents given at the same time, and those that act via the gastrointestinal tract. I generally withhold the fat-absorption blockers the day before surgery. Phentermine has the potential for catecholinergic reactions or sympathomimetic actions. I would put it in the category of herbal-type medicines and withhold it for at least 7 days.

Question from the audience: Can you comment on combination drugs such as losartan/hydrochlorothiazide on the morning of surgery?

Dr. Whinney: The ARB losartan may have more physiologic benefit than the diuretic, so I would prescribe a single dose of losartan the morning of surgery if I had decided to continue this class of medication for uncontrolled hypertension or concern over heart failure decompensation. The same is true for a beta-blocker/diuretic combination product; I will prescribe the beta-blocker component individually and tell the patient to take it the morning of surgery.

Question from the audience: I’m confused by the recommendation to stop hydrochlorothiazide. It’s a far less potent diuretic than furosemide. Does the risk of stopping it, with resulting blood pressure elevation, outweigh the risk of a mild hypotensive response because of a mild diuretic effect? I’m aware of no data on the risk of stopping hydrochlorothiazide—are you?

Dr. Whinney: There are no data. Again, the recommendation is based on the physiology of the drug, as well as on expert consensus and opinion. Since anesthesia has a vasodilatory effect with a hypotensive response, it’s probably reasonable to hold hydrochlorothiazide if its only indication is for hypertension. That’s the logic behind the recommendation. If you continue it the day of surgery, it may not necessarily hurt, but we’re not certain.

Question from the audience: The implication from your third case study was that alendronate should be held. What’s the basis of that recommendation?

Dr. Whinney: First, the patient has to be upright for 30 minutes after taking alendronate, which could be a problem on the morning of surgery. Also, withholding it will not impair short-term quality of life; it’s a weekly medication, so the patient can take her next dose once she’s up and ambulatory.

Question from the audience: What do you for young women on oral contraceptives? I’m lucky if I see them within 7 days of surgery.

Dr. Whinney: You’re bringing up the concern with exogenous hormones and the risk of venous thrombo­embolism (VTE), a risk that clearly is increased with the hypercoagulable milieu of surgery. The recommendation is to stop hormone therapy 30 to 45 days prior to surgery in these patients. As you note, however, we don’t get the chance to see patients during that window of opportunity. So the question is whether stopping hormones within a shorter time period results in an incremental benefit. And that is not necessarily the case. These patients should be seen as being at risk for VTE and be given appropriate VTE prophylaxis. In fact, in the similar context of menopausal hormone therapy, a study among women undergoing orthopedic surgery showed that as long as they received appropriate VTE prophylaxis, there was no significant difference in VTE rates between the women whose hormone therapy was withheld versus those who continued it.²⁶

Question from the audience: Are there concerns about withdrawal in patients with peripheral vascular disease treated with cilostazol or pentoxifylline?

Dr. Whinney: It’s not particularly well studied. Guidelines from the American College of Physicians suggest to hold these agents for elective surgeries.²⁷ With respect to antiplatelet therapies, O’Riordan et al did a systematic review of 99 articles pertaining to antiplatelet agents in the perioperative period and concluded that aspirin should not be stopped in patients going for surgery.²⁸ In vascular surgery, antiplatelet agents may help promote graft patency.

As a hospitalist who practices in a perioperative clinic, I probably spend more of my time with patients reviewing and discussing the medications they are taking than on any other single subject. Surgical patients—many of whom are elderly—commonly are on multiple medications, have renal or hepatic disease that can alter drug metabolism, and may not be adequately educated about their medication regimens.

Patient safety is the overriding concern behind perioperative medication management, consistent with the medication-related objectives in the Joint Commission’s 2009 National Patient Safety Goals.¹ The increasing surgical burden that comes with an aging population, along with rising expectations for functional recovery, has likewise elevated the importance of perioperative medication management.

Despite these demands, there is scant evidence from randomized controlled trials to directly guide perioperative medication management. For this reason, recommendations in this area rely largely on other forms of evidence, including expert consensus, case reports, in vitro studies, recommendations from pharmaceutical companies, and other known data (pharmacokinetics, drug interactions with anesthetic agents, and effects of the agent on the primary disease and on perioperative risk).

This article reviews general principles of perioperative medication management and then presents four case vignettes to explore perioperative recommendations for a number of common medication classes. It is not intended as a comprehensive review of the perioperative management of all medications, as numerous classes (antiplatelets, beta-blockers, oral hypogycemic agents, insulin, statins) are discussed in detail elsewhere in this proceedings supplement.

GENERAL CONSIDERATIONS IN MEDICATION MANAGEMENT

A comprehensive medication history is fundamental

Effective perioperative management of medications requires an understanding of the patient and his or her comorbidities so that the risk of perioperative decompensation can be gauged. This understanding stems from a thorough medical history that includes a comprehensive medication history to provide a complete inventory of the following:

• All prescription medications
• All over-the-counter (OTC) agents (including nonsteroidal anti-inflammatory drugs [NSAIDs])
• All vitamins
• All herbal medications.

When to stop, when to resume?

Guidance on stopping and resuming medications in the perioperative period is relatively absent from the literature. General considerations include the following:

• The potential for withdrawal when stopping a medication
• The progression of disease with interruption of drug therapy
• The potential for interactions with anesthetic agents if the medication is continued.

Withdrawal potential

Abrupt discontinuation of some drugs may lead to unnecessary complications due to the potential for withdrawal. Common medications that have been associated with withdrawal symptoms are selective serotonin reuptake inhibitors (SSRIs), beta-blockers, clonidine, statins, and corticosteroids.² A recent systematic literature review concluded that continuation of chronic corticosteroid therapy without supplemental (stress) doses of corticosteroids is appropriate unless patients have primary disease of the hypothalamic-pituitary-adrenal axis, in which case perioperative stress dosing is recommended to avoid acute adrenal insufficiency (addisonian crisis).³

Patients on chronic drugs are more likely to have complications

In a medication survey of 1,025 patients admitted to a general surgery unit, Kennedy et al reported that 49% of the patients were taking medications (other than vitamins) unrelated to their surgical procedure.⁴ Even while this percentage is considerably lower than what I observe in my practice, this study showed that medication use has important perioperative consequences⁴:

• The odds ratio for a postoperative complication was 2.7 (95% CI, 1.76–4.04) if patients were taking a drug unrelated to their surgery.
• The risk of a complication was particularly elevated if patients were taking cardiovascular drugs or agents that act on the central nervous system; if patients were on NPO (“nothing by mouth”) orders for more than 24 hours before surgery; and if the operation was more than 1 hour in duration. These findings could reflect destabilization of the disease processes for which the patients were taking chronic medications that required interruption.

Unintended discontinuation of chronic drugs

Stopping a chronic medication for a surgical procedure raises the possibility that its resumption could be overlooked, especially since medical errors are particularly common in the transition between health care settings following hospital discharge. A population-based cohort study among all elderly patients discharged from Ontario, Canada, hospitals over a 5½-year period found that 11.4% of patients undergoing elective surgery did not resume their indicated chronic warfarin therapy within 6 months after its presurgical discontinuation.⁵ Although 6-month rates of unintended failure to resume therapy were lower for statins (4%) and ophthalmic beta-blocker drops (8%),⁵ these findings underscore that drug discontinuation always carries a risk that therapy might not be resumed as indicated.

Additional considerations

Stress response to surgery. Decisions about perioperative drug therapy should always take into account the stress response to surgery and the challenge it presents to homeostasis in the face of increased sympathetic tone and release of pituitary hormones.

Unreliable absorption of oral medications. Surgery and the postoperative state can lead to unreliable absorption of oral drugs for any of a number of reasons: villous atrophy, diminished blood flow to the gut, edema, mucosal ischemia, diminished motility from postoperative ileus, and use of narcotics.⁶

Take-away general principles

The following principles can be applied to guide peri­operative medication management in a general sense⁷:

• Continue medications with withdrawal potential
• Discontinue medications that increase surgical risk and are not essential for short-term quality of life
• Use clinical judgment when neither of the above two principles applies, but be mindful that many other medications are given in the narrow perioperative time window and that metabolism and elimination of chronic drugs may be altered.

A 55-year-old man with severe osteoarthritis is scheduled for total hip arthroplasy in 2 days. He stopped his aspirin (325 mg/day) 1 week ago but continued taking ibuprofen 600 three times daily with food, explaining that “no one told me to stop.” His last dose was yesterday evening.

Question: What should you do?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop the ibuprofen now

C. Check his bleeding time and proceed if normal

D. Just tell the patient to stop the ibuprofen now

E. Proceed to the operating room regardless of the ibuprofen dose

The best approach would be to notify the surgeon and tell the patient to stop the ibuprofen now. NSAIDs such as ibuprofen reversibly inhibit platelet cyclooxygenase (COX), diminish thromboxane A₂ production, diminish platelet aggregation, and can increase bleeding time measurement and overall bleeding risk. They can induce renal failure in combination with other drugs, especially in the setting of hypotension.^8,9 COX-2 inhibitors have less effect on platelet function but retain the potential for renal toxicity and also confer well-known cardio­vascular risks.

In the past, NSAIDs were typically held for 7 days before surgery, but this practice was not supported with much evidence. In vitro assessment indicates that platelet function normalizes within 24 hours after cessation of regular ibuprofen or dexibuprofen in healthy individuals.^10,11

Since NSAIDs vary in their effect on bleeding time, which does not correlate well with elimination half-life, a general recommendation is to stop most NSAIDs at least 3 days before surgery.

CASE 2: A PATIENT ON MULTIPLE CARDIOVASCULAR DRUGS

A 67-year-old man with dilated cardiomyopathy and an ejection fraction of 25% (well compensated) is scheduled for a laparoscopic cholecystectomy tomorrow. He is taking lisinopril (40 mg/day), irbesartan (150 mg/day), and furosemide (80 mg/day).

Question: What is your advice?

A. Call the surgeon and cancel the surgery

B. Call the surgeon to notify, and tell the patient to stop his medications now

C. Hold all of the above medications on the morning of surgery

D. Proceed to the operating room with the usual doses of his medications on the morning of surgery

The best approach is to withhold these medications on the morning of surgery.

Diuretics are typically held on the morning of surgery because of the potential for hypovolemia and electrolyte depletion.

Angiotensin-converting enzyme (ACE) inhibitors intensify the hypotensive effects of anesthesia induction. Because angiotensin II plays a key role in maintaining circulating volume in response to stressors, volume deficits can occur in ACE inhibitor-treated patients as angiotensin II cannot compensate for venous pooling of blood, resulting in diminished cardiac output and arterial hypotension. However, continued renin-angiotensin system suppression may protect regional circulation, as has been demonstrated by reduced release of cardiac enzymes with ACE inhibitor continuation (compared with interruption) in cardiac surgery patients. ACE inhibitors also have a renal protective effect, preserving glomerular filtration rate in patients undergoing aortic abdominal aneurysm repair or coronary artery bypass graft surgery. Hypotension with ACE inhibition is treatable with sympathomimetics, alpha-agonists, and intravenous fluids.^12–15

If a patient’s ACE inhibitor is stopped, be prepared for rebound postoperative hypertension. The probability of postoperative atrial fibrillation is also increased with ACE inhibitor interruption.¹⁴ In patients with left ventricular dysfunction undergoing noncardiac vascular surgery, continued ACE inhibition is associated with reduced mortality.¹⁶ These data argue, at the very least, for prompt resumption of ACE inhibitors after surgery.

Angiotensin receptor blockers (ARBs) have largely the same clinical benefits as do ACE inhibitors. These agents also increase the risk of hypotension upon induction of anesthesia, and this hypotension is not as responsive to conventional vasopressors such as ephedrine and phenylephrine; a better response is achieved with vasopressin.¹⁵ In light of the long half-life of ARBs, current thinking is to withhold them 24 hours before surgery.

Rosenman et al recently published a meta-analysis of five studies assessing the effects of continuing or withholding ACE inhibitors and ARBs in the preoperative period.¹⁷ They found a statistically significant increase in the incidence of perioperative hypotension in patients in whom the drugs were continued compared with those in whom the drugs were withheld (relative risk = 1.50; 95% CI, 1.15–1.96), but there was no significant difference in the rate of perioperative MI between the two groups. Notably, the indication for ACE inhibitor or ARB use in all of the studies was hypertension, not heart failure.

My approach to the perioperative management of ACE inhibitors and ARBs is to withhold them on the morning of surgery (in the case of ARBs, 24 hours prior to surgery) if their only indication is for hypertension and if the patient’s blood pressure is well controlled. If the patient has another indication for these agents or has hypertension that is not well controlled, I am inclined to continue these agents but will first discuss the decision with the anesthesiologist.

A 68-year-old woman with a history of hypertension, osteoarthritis, and osteoporosis is scheduled for total hip replacement in 7 days. Her medications include atenolol, hydrochlorothiazide, and alendronate. She also reports taking some natural herbal medications. She does not recall their names initially but calls back with the names: ginkgo biloba for her memory and echinacea for her immune system.

Question: What are your recommendations?

A. Stop all medications now except atenolol and proceed to surgery

B. Stop the herbals now but take all other medications on the morning of surgery

C. Stop the herbals now and take only atenolol on the morning of surgery

D. Continue all medications now and take atenolol and the herbals on the morning of surgery

E. Cancel the surgery and call an herbalist for guidance

The best strategy is to stop the herbals now and tell her to take only atenolol (a beta-blocker) on the morning of surgery.

Because the US Food and Drug Administration (FDA) does not regulate herbal products, the contents of these products can vary widely. For example, an analysis using mass spectrometry of 50 commercial ginseng products from 11 countries found that the ginseng content varied from 0% (six preparations) to 9%.¹⁹ Catecholamine-type compounds were found in some of the products.¹⁹

Because of the uncertainty over their actual contents, herbal medications should be stopped at least 7 days prior to surgery. If a patient is still taking herbal supplements on the day before surgery, I typically alert the anesthesiologist and surgeon.

CASE 4: A PATIENT ON MULTIPLE PSYCHOTROPICS

A 38-year-old woman with a history of severe major depression is scheduled for a mastectomy for breast cancer the next day. Her medications include fluoxetine, lorazepam, and phenelzine, all of which she has been taking for many years.

Question: What is your course of action?

A. Call the surgeon and cancel the surgery

B. Call the surgeon and notify the day-of-surgery anesthesiologist that the patient is taking these agents

C. Stop all the medications now and proceed to the operating room

D. Request a psychiatric consult for an alternative drug regimen

E. Proceed and advise the patient to take all of these agents on the morning of surgery

My approach would be to notify the day-of-surgery anesthesiologist, specifically about the phenelzine, which is a monoamine oxidase (MAO) inhibitor (see below). The other two agents can be taken on the morning of surgery, although fluoxetine has a long half-life, so missing a dose should not be problematic, and lorazepam can be given intravenously if needed.

SSRIs, including fluoxetine, are generally safe peri­operatively. Serotonin depletion from platelets, however, increases the risk of bleeding, especially gastrointestinal bleeding, when SSRIs are used with NSAIDs.^20–22 A neurosurgical procedure may therefore be especially risky in patients who have not stopped their SSRI if they are also taking an NSAID or an herbal medication that may increase the risk of bleeding. The caveat to stopping SSRIs is the potential for a minor withdrawal syndrome.

Tricyclic antidepressants inhibit the reuptake of norepinephrine and serotonin and may increase the action of sympathomimetics. Although arrhythmias are thought to be a concern with tricyclics, there are no reported cases of association in the literature. In general, I advise continuing triclyclics perioperatively, especially in patients who are on high doses.

Benzodiazepines, including lorazepam, are safe to use perioperatively, and a potential for withdrawal symptoms (hypertension, agitation, delirium, seizures) argues against their discontinuation. Chronic benzodiazepine use may increase anesthetic requirements.

Antipsychotic agents, which include haloperidol, olanzapine, risperidone, and ziprasidone, have multiple routes of administration—intramuscular, oral, sublingual, and intravenous. These agents are generally safe to use in the perioperative period.

MAO inhibitors, including phenelzine, are no longer commonly used and are typically reserved for the treatment of refractory depression. But they merit attention, as their use can cause accumulation of biogenic amines in the central and autonomic nervous systems. There are two types of MAO reactions—excitatory and depressive. Excitatory reactions lead to serotonin syndrome. Depressive reactions induce inhibition of hepatic microsomal enzymes, leading to narcotic accumulation and increased sedation.²³

MAO inhibitors are also of concern because of their many drug interactions. When used with indirect sympathomimetics such as ephedrine, they promote a massive release of stored norepinephrine, leading to severe hypertension. When used with opioids like meperidine and dextromethorphan, MAO inhibitors are associated with a serotonin syndrome characterized by agitation, headache, fever, seizures, coma, and death.

Discontinuing MAO inhibitors before the day of surgery is no longer universally recommended, due to the risk of precipitating an exacerbation of major depression. Safe anesthetic regimens in the setting of MAO inhibitors involve avoidance of meperidine (morphine and fentanyl are safe) and use of only direct-acting sympathomimetics.

A good medication history that includes herbal and OTC products is essential for safe induction of anesthesia and optimization of outcomes during and following surgery. In general, medications with the potential to induce withdrawal symptoms should be continued. The use of nonessential medications that can increase surgical risk should be discontinued. If neither of these conditions applies, consider the patient’s risk profile and the risk of the procedure when making perioperative management decisions. Be mindful of withdrawal syndromes and resume medications with the potential for such syndromes as soon as possible.

DISCUSSION

Comment from the audience: In regard to your comment that diuretics are typically held on the morning of surgery, my institution recently completed a randomized placebo-controlled trial (publication is pending) in which we studied the effect of continuing or not continuing furosemide preoperatively. We found no difference in the occurrence of intraoperative hypotension between the two groups. It will be interesting to see if these findings change practice over time.

Dr. Whinney: It’s good to know that hypotension is not a concern with furosemide, but the issue here is not just blood pressure but electrolyte abnormalities that could predispose to arrhythmias. The patients who concern me are those who haven’t been seen by a physician for a while and may be on high doses of furosemide. I would scrutinize such patients closely.

Question from the audience: We see a number of patients on methotrexate and other disease-modifying rheumatologic drugs. Can you comment on the peri­operative management of these medications?

Dr. Whinney: Methotrexate has caused some anxiety over the risk of infection, but the literature does not support such concern.²⁴ In fact, it appears that continuing methotrexate is probably advisable because the risk of decompensation of the disease may be worse than the potential infectious risks. The only caveat is the patient with renal insufficiency, in whom the recommendation is to withhold methotrexate for 2 weeks before surgery. While most rheumatologists favor withholding disease-modifying drugs perioperatively, a recent systematic review showed no increased risk of either total or infectious complications with use of immunomodulators including infliximab, azathioprine, and cyclosporine.²⁵ It is still reasonable and prudent to discuss this issue with the patient’s rheumatologist. Hydroxychloroquine is safe to continue.

Comment from the audience: First, I would like to urge everyone to be mindful of medication-related indications for preoperative testing. There are many psychotropic drugs that prolong the QT interval and thus constitute an indication for a baseline electrocardiogram prior to surgery. Second, I believe there is a mythology in the perioperative community about the bleeding risk associated with omega-3 fatty acids and vitamin E. Can you comment on the bleeding risks associated with each?

Dr. Whinney: There are few data; the fear is based purely on the potential of these compounds to cause bleeding. Neither is beneficial for short-term quality of life or for chronic prevention, and there’s no withdrawal syndrome from either. So I generally withhold them, but if the patient is still taking them up to the day of surgery, it doesn’t merit postponing surgery. I generally let the surgeon or the nurse know, and it tends not to be a big deal.

Question from the audience: Do you stop herbal teas, energy drinks, and diet medications such as phentermine prior to surgery?

Dr. Whinney: You need to know which diet medications the patient is taking. The problem with many of the OTC products is that they may or may not be considered drugs, so they may not be approved by the FDA and thus you don’t know what the patient is actually taking. For the most part, a diet medication does not contribute to short-term quality of life. My aim is to get the patient through surgery as safely as possible, so if a patient is taking an agent with ingredients, known or unknown, with an interaction potential, then I will stop it.

The two types of diet agents are those that block the absorption of fat, which could interact with other oral agents given at the same time, and those that act via the gastrointestinal tract. I generally withhold the fat-absorption blockers the day before surgery. Phentermine has the potential for catecholinergic reactions or sympathomimetic actions. I would put it in the category of herbal-type medicines and withhold it for at least 7 days.

Question from the audience: Can you comment on combination drugs such as losartan/hydrochlorothiazide on the morning of surgery?

Dr. Whinney: The ARB losartan may have more physiologic benefit than the diuretic, so I would prescribe a single dose of losartan the morning of surgery if I had decided to continue this class of medication for uncontrolled hypertension or concern over heart failure decompensation. The same is true for a beta-blocker/diuretic combination product; I will prescribe the beta-blocker component individually and tell the patient to take it the morning of surgery.

Question from the audience: I’m confused by the recommendation to stop hydrochlorothiazide. It’s a far less potent diuretic than furosemide. Does the risk of stopping it, with resulting blood pressure elevation, outweigh the risk of a mild hypotensive response because of a mild diuretic effect? I’m aware of no data on the risk of stopping hydrochlorothiazide—are you?

Dr. Whinney: There are no data. Again, the recommendation is based on the physiology of the drug, as well as on expert consensus and opinion. Since anesthesia has a vasodilatory effect with a hypotensive response, it’s probably reasonable to hold hydrochlorothiazide if its only indication is for hypertension. That’s the logic behind the recommendation. If you continue it the day of surgery, it may not necessarily hurt, but we’re not certain.

Question from the audience: The implication from your third case study was that alendronate should be held. What’s the basis of that recommendation?

Dr. Whinney: First, the patient has to be upright for 30 minutes after taking alendronate, which could be a problem on the morning of surgery. Also, withholding it will not impair short-term quality of life; it’s a weekly medication, so the patient can take her next dose once she’s up and ambulatory.

Question from the audience: What do you for young women on oral contraceptives? I’m lucky if I see them within 7 days of surgery.

Dr. Whinney: You’re bringing up the concern with exogenous hormones and the risk of venous thrombo­embolism (VTE), a risk that clearly is increased with the hypercoagulable milieu of surgery. The recommendation is to stop hormone therapy 30 to 45 days prior to surgery in these patients. As you note, however, we don’t get the chance to see patients during that window of opportunity. So the question is whether stopping hormones within a shorter time period results in an incremental benefit. And that is not necessarily the case. These patients should be seen as being at risk for VTE and be given appropriate VTE prophylaxis. In fact, in the similar context of menopausal hormone therapy, a study among women undergoing orthopedic surgery showed that as long as they received appropriate VTE prophylaxis, there was no significant difference in VTE rates between the women whose hormone therapy was withheld versus those who continued it.²⁶

Question from the audience: Are there concerns about withdrawal in patients with peripheral vascular disease treated with cilostazol or pentoxifylline?

Dr. Whinney: It’s not particularly well studied. Guidelines from the American College of Physicians suggest to hold these agents for elective surgeries.²⁷ With respect to antiplatelet therapies, O’Riordan et al did a systematic review of 99 articles pertaining to antiplatelet agents in the perioperative period and concluded that aspirin should not be stopped in patients going for surgery.²⁸ In vascular surgery, antiplatelet agents may help promote graft patency.

Supplement Editor:
Amir K. Jaffer, MD, FHM

Associate Editors:
David L. Hepner, MD, and Franklin A. Michota, MD, FHM

Contents

Public reporting and pay-for-performance programs in perioperative medicine
Peter Lindenauer, MD MSc

Cardiac risk stratification for noncardiac surgery: Update from the American College of Cardiology/American Heart Association 2007 guidelines
Lee A. Fleisher, MD

Perioperative care of the elderly patient: An update
Robert M. Palmer, MD, MPH

The role of testing in the preoperative evaluation
David L. Hepner, MD

Perioperative fluid management: Progress despite lingering controversies
Mark A. Hamilton, MBBS, MRCP, FRCA

Giving anesthesiologists what they want: How to write a useful preoperative consult
David Lubarsky, MD, MBA, and Keith Candiotti, MD

Perioperative management of warfarin and antiplatelet therapy
Amir K. Jaffer, MD, FHM

Prevention of venous thromboembolism after surgery
Franklin A. Michota, MD, FHM

Perioperative management of diabetes: Translating evidence into practice
Luigi F. Meneghini, MD, MBA

Postoperative pulmonary complications: An update on risk assessment and reduction
Gerald W. Smetana, MD

Postoperative gastrointestinal tract dysfunction: An overview of causes and management strategies
Michael G. (Monty) Mythen, MD

Case studies in perioperative management: Challenges, controversies, and common ground
Steven L. Cohn, MD, and BobbieJean Sweitzer, MD

Statins and noncardiac surgery: Current evidence and practical considerations
Don Poldermans, MD, PhD

The experts debate: perioperative beta-blockade for noncardiac surgery patients—proven safe or not?
Don Poldermans, MD, PhD, and P.J. Devereaux, MD, PhD

Perioperative considerations for patients with liver disease
Paul Martin, MD

Perioperative management of obstructive sleep apnea: Ready for prime time?
Shirin Shafazand, MD, MS

Nuts and bolts of preoperative clinics: The view from three institutions
Angela M. Bader, MD, MPH; BobbieJean Sweitzer, MD; and Ajay Kumar, MD

Perioperative management of anemia: Limits of blood transfusion and alternatives to it
Ajay Kumar, MD

Medicolegal issues in perioperative medicine: Lessons from real cases
Franklin A. Michota, MD, FHM, and Matthew J. Donnelly, Esq

Perioperative medication management: General principles and practical applications
Christopher Whinney, MD

Supplement Editor:
Amir K. Jaffer, MD, FHM

Associate Editors:
David L. Hepner, MD, and Franklin A. Michota, MD, FHM

Contents

Public reporting and pay-for-performance programs in perioperative medicine
Peter Lindenauer, MD MSc

Cardiac risk stratification for noncardiac surgery: Update from the American College of Cardiology/American Heart Association 2007 guidelines
Lee A. Fleisher, MD

Perioperative care of the elderly patient: An update
Robert M. Palmer, MD, MPH

The role of testing in the preoperative evaluation
David L. Hepner, MD

Perioperative fluid management: Progress despite lingering controversies
Mark A. Hamilton, MBBS, MRCP, FRCA

Giving anesthesiologists what they want: How to write a useful preoperative consult
David Lubarsky, MD, MBA, and Keith Candiotti, MD

Perioperative management of warfarin and antiplatelet therapy
Amir K. Jaffer, MD, FHM

Prevention of venous thromboembolism after surgery
Franklin A. Michota, MD, FHM

Perioperative management of diabetes: Translating evidence into practice
Luigi F. Meneghini, MD, MBA

Postoperative pulmonary complications: An update on risk assessment and reduction
Gerald W. Smetana, MD

Postoperative gastrointestinal tract dysfunction: An overview of causes and management strategies
Michael G. (Monty) Mythen, MD

Case studies in perioperative management: Challenges, controversies, and common ground
Steven L. Cohn, MD, and BobbieJean Sweitzer, MD

Statins and noncardiac surgery: Current evidence and practical considerations
Don Poldermans, MD, PhD

The experts debate: perioperative beta-blockade for noncardiac surgery patients—proven safe or not?
Don Poldermans, MD, PhD, and P.J. Devereaux, MD, PhD

Perioperative considerations for patients with liver disease
Paul Martin, MD

Perioperative management of obstructive sleep apnea: Ready for prime time?
Shirin Shafazand, MD, MS

Nuts and bolts of preoperative clinics: The view from three institutions
Angela M. Bader, MD, MPH; BobbieJean Sweitzer, MD; and Ajay Kumar, MD

Perioperative management of anemia: Limits of blood transfusion and alternatives to it
Ajay Kumar, MD

Medicolegal issues in perioperative medicine: Lessons from real cases
Franklin A. Michota, MD, FHM, and Matthew J. Donnelly, Esq

Perioperative medication management: General principles and practical applications
Christopher Whinney, MD

Supplement Editor:
Amir K. Jaffer, MD, FHM

Associate Editors:
David L. Hepner, MD, and Franklin A. Michota, MD, FHM

Contents

Public reporting and pay-for-performance programs in perioperative medicine
Peter Lindenauer, MD MSc

Cardiac risk stratification for noncardiac surgery: Update from the American College of Cardiology/American Heart Association 2007 guidelines
Lee A. Fleisher, MD

Perioperative care of the elderly patient: An update
Robert M. Palmer, MD, MPH

The role of testing in the preoperative evaluation
David L. Hepner, MD

Perioperative fluid management: Progress despite lingering controversies
Mark A. Hamilton, MBBS, MRCP, FRCA

Giving anesthesiologists what they want: How to write a useful preoperative consult
David Lubarsky, MD, MBA, and Keith Candiotti, MD

Perioperative management of warfarin and antiplatelet therapy
Amir K. Jaffer, MD, FHM

Prevention of venous thromboembolism after surgery
Franklin A. Michota, MD, FHM

Perioperative management of diabetes: Translating evidence into practice
Luigi F. Meneghini, MD, MBA

Postoperative pulmonary complications: An update on risk assessment and reduction
Gerald W. Smetana, MD

Postoperative gastrointestinal tract dysfunction: An overview of causes and management strategies
Michael G. (Monty) Mythen, MD

Case studies in perioperative management: Challenges, controversies, and common ground
Steven L. Cohn, MD, and BobbieJean Sweitzer, MD

Statins and noncardiac surgery: Current evidence and practical considerations
Don Poldermans, MD, PhD

The experts debate: perioperative beta-blockade for noncardiac surgery patients—proven safe or not?
Don Poldermans, MD, PhD, and P.J. Devereaux, MD, PhD

Perioperative considerations for patients with liver disease
Paul Martin, MD

Perioperative management of obstructive sleep apnea: Ready for prime time?
Shirin Shafazand, MD, MS

Nuts and bolts of preoperative clinics: The view from three institutions
Angela M. Bader, MD, MPH; BobbieJean Sweitzer, MD; and Ajay Kumar, MD

Perioperative management of anemia: Limits of blood transfusion and alternatives to it
Ajay Kumar, MD

Medicolegal issues in perioperative medicine: Lessons from real cases
Franklin A. Michota, MD, FHM, and Matthew J. Donnelly, Esq

Perioperative medication management: General principles and practical applications
Christopher Whinney, MD

Hypertension is difficult to diagnose, and its treatment is difficult to monitor optimally on the basis of traditional office blood pressure measurements. To better protect our patients from the effects of undiagnosed or poorly controlled hypertension, we need to consider other options, such as ambulatory 24-hour blood pressure monitoring, automated measurement in the office, measurement in the patient’s home, and devices that analyze the peripheral pulse wave to estimate the central blood pressure and other indices of arterial stiffness.

MANUAL OFFICE MEASUREMENT HAS INHERENT LIMITATIONS

Office blood pressure measurements do provide enormous information about cardiovascular risk and the risk of death, as shown in epidemiologic studies. A meta-analysis¹ of 61 prospective observational studies that included more than 1 million patients showed that office blood pressure levels clearly correlate with increased risk of death from cardiovascular disease and stroke.

But blood pressure is a dynamic measure with inherent minute-to-minute variability, and measurement will not be accurate if the correct technique is not followed. Traditional office sphygmomanometry is a snapshot and does not accurately reflect a patient’s blood pressure in the real world and in real time.

Recently, unique patterns of blood pressure have been identified that may not be detected in the physician’s office. It is clear from several clinical trials that some patients’ blood pressure is transiently elevated in the first few minutes during office measurements (the “white coat effect”). In addition, when office measurements are compared with out-of-office measurements, several patterns of hypertension emerge that have prognostic value. These patterns are white coat hypertension, masked hypertension, nocturnal hypertension, and failure of the blood pressure to dip during sleep.

WHITE COAT EFFECT

The white coat effect is described as a transient elevation in office blood pressure caused by an alerting reaction when the pressure is measured by a physician or a nurse. It may last for several minutes. The magnitude of blood pressure elevation has been noted to be higher when measured by a physician than when measured by a nurse. Multiple blood pressure measurements taken over 5 to 10 minutes help eliminate the white coat effect. In a recent study,² 36% of patients with hypertension demonstrated the white coat effect.

In a study by Mancia et al,³ 46 patients underwent intra-arterial blood pressure monitoring for 2 days, during which time a physician or a nurse would check their blood pressure repeatedly over 10 minutes. This study found that most patients demonstrated the white coat effect: the blood pressure was higher in the first few measurements, but came down after 5 minutes. The white coat effect was as much as 22.6 ± 1.8 mm Hg when blood pressure was measured by a physician and was lower when measured by a nurse.

WHITE COAT HYPERTENSION

In contrast to the white coat effect, which is transient, white coat hypertension is defined as persistent elevation of office blood pressure measurements with normal blood pressure levels when measured outside the physician’s office. Depending on the population sampled, the prevalence of white coat hypertension ranges from 12% to 20%, but this is understandably difficult or almost impossible to detect with traditional office blood pressure measurements alone.^4–7

MASKED HYPERTENSION

Patients with normal blood pressure in the physician’s office but high blood pressure during daily life were found to have a higher risk of cardiovascular events. This condition is called masked hypertension.⁸ For clinicians, the danger lies in underestimating the patient’s risk of cardiovascular events and, thus, undertreating the hypertension. Preliminary data on masked hypertension show that the rates of end-organ damage and cardiovascular events are slightly higher in patients with masked hypertension than in patients with sustained hypertension.

NOCTURNAL HYPERTENSION

Elevated nighttime blood pressure (>125/75 mm Hg) is considered nocturnal hypertension and is generally considered a subgroup of masked hypertension.⁹

In the African American Study of Kidney Disease and Hypertension (AASK),^10,11 although most patients achieved their blood pressure goal during the trial, they were noted to have relentless progression of renal disease. On ambulatory 24-hour blood pressure monitoring during the cohort phase of the study,¹⁰ a high prevalence of elevated nighttime blood pressure (66%) was found. Further analysis showed that the elevated nighttime blood pressure was associated with worse hypertension-related end-organ damage. It is still unclear if lowering nighttime blood pressure improves clinical outcomes in this high-risk population.

DIPPING VS NONDIPPING

The mean blood pressure during sleep should normally decrease by 10% to 20% compared with daytime readings. “Nondipping,” ie, the lack of this nocturnal dip in blood pressure, carries a higher risk of death from cardiovascular causes, even if the person is otherwise normotensive.^12,13 Nondipping is commonly noted in African Americans, patients with diabetes, and those with chronic kidney disease.

A study by Lurbe et al¹⁴ of patients with type 1 diabetes mellitus who underwent ambulatory 24-hour blood pressure monitoring found that the onset of the nondipping phenomenon preceded microalbuminuria (a risk factor for kidney disease). Data from our institution¹⁵ showed that nondipping was associated with a greater decline in glomerular filtration rate when compared with dipping.

The lack of reproducibility of a person’s dipping status has been a barrier in relying on this as a prognostic measure. White and Larocca¹⁶ found that only about half of the patients who appeared to be nondippers on one 24-hour recording still were nondippers on a second recording 4 to 8 weeks later. Compared with nondipping, nocturnal hypertension is a more stable blood pressure pattern that is being increasingly recognized in patients undergoing 24-hour blood pressure monitoring.

AUTOMATIC BLOOD PRESSURE DEVICES

An automated in-office blood pressure measurement device is one way to minimize the white coat effect and obtain a more accurate blood pressure assessment. Devices such as BpTRU (BpTRU Medical Devices Ltd, Coquitlam, BC, Canada) are programmed to take a series of automatic, oscillometric readings at regular intervals while the patient is left alone in a quiet room. BpTRU has been validated in several clinical trials and has been shown to overcome the white coat effect to some extent. Myers et al¹⁷ compared 24-hour blood pressure readings with those obtained by a family physician, by a research technician, and by the BpTRU device and found that the BpTRU readings were much closer to the average of awake blood pressure readings on 24-hour blood pressure monitoring.

AMBULATORY 24-HOUR BLOOD PRESSURE MONITORING

• Presence or absence of the nocturnal dip (the normal 10% to 20% drop in blood pressure at night during sleep)
• Morning surge (which in some studies was associated with higher incidence of stroke)
• Supine hypertension and sudden fluctuations in blood pressure seen in patients with autonomic failure.

Studies have shown that basing antihypertensive therapy on ambulatory 24-hour blood pressure monitoring results in better control of hypertension and lowers the rate of cardiovascular events.^18,19

Perloff et al¹⁸ found that in patients whose hypertension was considered well controlled on the basis of office blood pressure measurements, those with higher blood pressures on ambulatory 24-hour monitoring had higher cardiovascular morbidity and mortality rates.

More recently, Clement et al¹⁹ showed that patients being treated for hypertension who have higher average ambulatory 24-hour blood pressures had a higher risk of cardiovascular events and cardiovascular death.

After following 790 patients for 3.7 years, Verdecchia et al²⁰ concluded that controlling hypertension on the basis of ambulatory 24-hour blood pressure readings rather than traditional office measurements lowered the risk of cardiovascular disease.

‘Normal’ blood pressure on ambulatory 24-hour monitoring

It should be noted that the normal average blood pressure on ambulatory 24-hour monitoring tends to be lower than that on traditional office readings. According to the 2007 European guidelines,²¹ an average 24-hour blood pressure above the range of 125/80 to 130/80 mm Hg is considered diagnostic of hypertension.

The bottom line on ambulatory 24-hour monitoring: Not perfect, but helpful

Ambulatory 24-hour blood pressure monitoring is not perfect. It interferes with the patient’s activities and with sleep, and this can affect the readings. It is also expensive, and Medicare and Medicaid cover it only if the patient is diagnosed with white coat hypertension, based on stringent criteria that include three elevated clinic blood pressure measurements and two normal out-of-clinic blood pressure measurements and no evidence of end-organ damage. Despite these issues, almost all national guidelines for the management of hypertension recommend ambulatory 24-hour blood pressure monitoring to improve cardiovascular risk prediction and to measure the variability in blood pressure levels.

USING THE INTERNET IN MANAGING HYPERTENSION

Green et al²² studied a new model of care using home blood pressure monitoring via the Internet, and provided feedback and intervention to the patient via a pharmacist to achieve blood pressure goals. Patients measured their blood pressure at home on at least 2 days a week (two measurements each time), using an automatic oscillometric monitor (Omron Hem-705-CP, Kyoto, Japan), and entered the results in an electronic medical record on the Internet. In the intervention group, a pharmacist communicated with each patient by either phone or e-mail every 2 weeks, making changes to their antihypertensive regimens as needed.

Patients in the intervention group had an average reduction in blood pressure of 14 mm Hg from baseline, and their blood pressure was much better controlled compared with the control groups, who were being passively monitored or were receiving usual care based on office blood pressure readings.

MEASURING ARTERIAL STIFFNESS TO ASSES RISK OF END-ORGAN DAMAGE

Mean arterial blood pressure, derived from the extremes of systolic and diastolic pressure as measured with a traditional sphygmomanometer, is a product of cardiac output and total peripheral vascular resistance. In contrast, central aortic blood pressure, the central augmentation index, and pulse wave velocity are measures derived from brachial blood pressure as well as arterial pulse wave tracings. They provide additional information on arterial stiffness and help stratify patients at increased cardiovascular risk.

The art of evaluating the arterial pulse wave with the fingertips while examining a patient and diagnosing various ailments was well known and practiced by ancient Greek and Chinese physicians. Although this was less recognized in Western medicine, it was the pulse wave recording on a sphygmograph that was used to measure human blood pressure in the 19th century.²³ In the early 20th century, this art was lost with the invention of the mercury sphygmomanometer.

Arterial stiffness indices—ie, central aortic blood pressure, the central augmentation index, and pulse wave velocity—can now be measured noninvasively and have been shown to correlate very well with measurements obtained via a central arterial catheter. In the past, the only way to measure central blood pressure was directly via a central arterial catheter. New devices now measure arterial stiffness indices indirectly by applanation tonometry and pulse wave analysis (reviewed by O’Rourke et al²⁵).

Several trials have shown that these arterial indices have a better prognostic value than the mean arterial pressure or the brachial pulse pressure. For example, the Baltimore Longitudinal Study of Aging²⁶ followed 100 normotensive individuals for 5 years and found that those with a higher pulse wave velocity had a greater chance of developing incident hypertension. Other studies showed that pulse wave velocity and other indices of arterial stiffness are associated with dysfunction of the microvasculature in the brain, with higher cardiovascular risk, and a higher risk of death.

A major limitation in measuring these arterial stiffness indices is that they are derived values and require measurement of brachial blood pressure in addition to the pulse wave tracing.

Recent hypertension guidelines^21,27,28 released during the past 2 years in Europe, Latin America, and Japan have recommended measurement of arterial stiffness as part of a comprehensive evaluation of patients with hypertension.

EXCITING TIMES IN HYPERTENSION

These are exciting times in the field of hypertension. With advances in technology, we have new devices and techniques that provide a closer view of the hemodynamic changes and blood pressures experienced by vital organs. In addition, we can now go beyond the physician’s office and evaluate blood pressure changes that occur during the course of a usual day in a patient’s life. This enables us to make better decisions in the management of their hypertension, embodying Dr. Harvey Cushing’s teaching that the physician’s obligation is to “view the man in his world.”²⁹

Hypertension is difficult to diagnose, and its treatment is difficult to monitor optimally on the basis of traditional office blood pressure measurements. To better protect our patients from the effects of undiagnosed or poorly controlled hypertension, we need to consider other options, such as ambulatory 24-hour blood pressure monitoring, automated measurement in the office, measurement in the patient’s home, and devices that analyze the peripheral pulse wave to estimate the central blood pressure and other indices of arterial stiffness.

MANUAL OFFICE MEASUREMENT HAS INHERENT LIMITATIONS

Office blood pressure measurements do provide enormous information about cardiovascular risk and the risk of death, as shown in epidemiologic studies. A meta-analysis¹ of 61 prospective observational studies that included more than 1 million patients showed that office blood pressure levels clearly correlate with increased risk of death from cardiovascular disease and stroke.

But blood pressure is a dynamic measure with inherent minute-to-minute variability, and measurement will not be accurate if the correct technique is not followed. Traditional office sphygmomanometry is a snapshot and does not accurately reflect a patient’s blood pressure in the real world and in real time.

Recently, unique patterns of blood pressure have been identified that may not be detected in the physician’s office. It is clear from several clinical trials that some patients’ blood pressure is transiently elevated in the first few minutes during office measurements (the “white coat effect”). In addition, when office measurements are compared with out-of-office measurements, several patterns of hypertension emerge that have prognostic value. These patterns are white coat hypertension, masked hypertension, nocturnal hypertension, and failure of the blood pressure to dip during sleep.

WHITE COAT EFFECT

The white coat effect is described as a transient elevation in office blood pressure caused by an alerting reaction when the pressure is measured by a physician or a nurse. It may last for several minutes. The magnitude of blood pressure elevation has been noted to be higher when measured by a physician than when measured by a nurse. Multiple blood pressure measurements taken over 5 to 10 minutes help eliminate the white coat effect. In a recent study,² 36% of patients with hypertension demonstrated the white coat effect.

In a study by Mancia et al,³ 46 patients underwent intra-arterial blood pressure monitoring for 2 days, during which time a physician or a nurse would check their blood pressure repeatedly over 10 minutes. This study found that most patients demonstrated the white coat effect: the blood pressure was higher in the first few measurements, but came down after 5 minutes. The white coat effect was as much as 22.6 ± 1.8 mm Hg when blood pressure was measured by a physician and was lower when measured by a nurse.

WHITE COAT HYPERTENSION

In contrast to the white coat effect, which is transient, white coat hypertension is defined as persistent elevation of office blood pressure measurements with normal blood pressure levels when measured outside the physician’s office. Depending on the population sampled, the prevalence of white coat hypertension ranges from 12% to 20%, but this is understandably difficult or almost impossible to detect with traditional office blood pressure measurements alone.^4–7

MASKED HYPERTENSION

Patients with normal blood pressure in the physician’s office but high blood pressure during daily life were found to have a higher risk of cardiovascular events. This condition is called masked hypertension.⁸ For clinicians, the danger lies in underestimating the patient’s risk of cardiovascular events and, thus, undertreating the hypertension. Preliminary data on masked hypertension show that the rates of end-organ damage and cardiovascular events are slightly higher in patients with masked hypertension than in patients with sustained hypertension.

NOCTURNAL HYPERTENSION

Elevated nighttime blood pressure (>125/75 mm Hg) is considered nocturnal hypertension and is generally considered a subgroup of masked hypertension.⁹

In the African American Study of Kidney Disease and Hypertension (AASK),^10,11 although most patients achieved their blood pressure goal during the trial, they were noted to have relentless progression of renal disease. On ambulatory 24-hour blood pressure monitoring during the cohort phase of the study,¹⁰ a high prevalence of elevated nighttime blood pressure (66%) was found. Further analysis showed that the elevated nighttime blood pressure was associated with worse hypertension-related end-organ damage. It is still unclear if lowering nighttime blood pressure improves clinical outcomes in this high-risk population.

DIPPING VS NONDIPPING

The mean blood pressure during sleep should normally decrease by 10% to 20% compared with daytime readings. “Nondipping,” ie, the lack of this nocturnal dip in blood pressure, carries a higher risk of death from cardiovascular causes, even if the person is otherwise normotensive.^12,13 Nondipping is commonly noted in African Americans, patients with diabetes, and those with chronic kidney disease.

A study by Lurbe et al¹⁴ of patients with type 1 diabetes mellitus who underwent ambulatory 24-hour blood pressure monitoring found that the onset of the nondipping phenomenon preceded microalbuminuria (a risk factor for kidney disease). Data from our institution¹⁵ showed that nondipping was associated with a greater decline in glomerular filtration rate when compared with dipping.

The lack of reproducibility of a person’s dipping status has been a barrier in relying on this as a prognostic measure. White and Larocca¹⁶ found that only about half of the patients who appeared to be nondippers on one 24-hour recording still were nondippers on a second recording 4 to 8 weeks later. Compared with nondipping, nocturnal hypertension is a more stable blood pressure pattern that is being increasingly recognized in patients undergoing 24-hour blood pressure monitoring.

AUTOMATIC BLOOD PRESSURE DEVICES

An automated in-office blood pressure measurement device is one way to minimize the white coat effect and obtain a more accurate blood pressure assessment. Devices such as BpTRU (BpTRU Medical Devices Ltd, Coquitlam, BC, Canada) are programmed to take a series of automatic, oscillometric readings at regular intervals while the patient is left alone in a quiet room. BpTRU has been validated in several clinical trials and has been shown to overcome the white coat effect to some extent. Myers et al¹⁷ compared 24-hour blood pressure readings with those obtained by a family physician, by a research technician, and by the BpTRU device and found that the BpTRU readings were much closer to the average of awake blood pressure readings on 24-hour blood pressure monitoring.

AMBULATORY 24-HOUR BLOOD PRESSURE MONITORING

• Presence or absence of the nocturnal dip (the normal 10% to 20% drop in blood pressure at night during sleep)
• Morning surge (which in some studies was associated with higher incidence of stroke)
• Supine hypertension and sudden fluctuations in blood pressure seen in patients with autonomic failure.

Studies have shown that basing antihypertensive therapy on ambulatory 24-hour blood pressure monitoring results in better control of hypertension and lowers the rate of cardiovascular events.^18,19

Perloff et al¹⁸ found that in patients whose hypertension was considered well controlled on the basis of office blood pressure measurements, those with higher blood pressures on ambulatory 24-hour monitoring had higher cardiovascular morbidity and mortality rates.

More recently, Clement et al¹⁹ showed that patients being treated for hypertension who have higher average ambulatory 24-hour blood pressures had a higher risk of cardiovascular events and cardiovascular death.

After following 790 patients for 3.7 years, Verdecchia et al²⁰ concluded that controlling hypertension on the basis of ambulatory 24-hour blood pressure readings rather than traditional office measurements lowered the risk of cardiovascular disease.

‘Normal’ blood pressure on ambulatory 24-hour monitoring

It should be noted that the normal average blood pressure on ambulatory 24-hour monitoring tends to be lower than that on traditional office readings. According to the 2007 European guidelines,²¹ an average 24-hour blood pressure above the range of 125/80 to 130/80 mm Hg is considered diagnostic of hypertension.

The bottom line on ambulatory 24-hour monitoring: Not perfect, but helpful

Ambulatory 24-hour blood pressure monitoring is not perfect. It interferes with the patient’s activities and with sleep, and this can affect the readings. It is also expensive, and Medicare and Medicaid cover it only if the patient is diagnosed with white coat hypertension, based on stringent criteria that include three elevated clinic blood pressure measurements and two normal out-of-clinic blood pressure measurements and no evidence of end-organ damage. Despite these issues, almost all national guidelines for the management of hypertension recommend ambulatory 24-hour blood pressure monitoring to improve cardiovascular risk prediction and to measure the variability in blood pressure levels.

USING THE INTERNET IN MANAGING HYPERTENSION

Green et al²² studied a new model of care using home blood pressure monitoring via the Internet, and provided feedback and intervention to the patient via a pharmacist to achieve blood pressure goals. Patients measured their blood pressure at home on at least 2 days a week (two measurements each time), using an automatic oscillometric monitor (Omron Hem-705-CP, Kyoto, Japan), and entered the results in an electronic medical record on the Internet. In the intervention group, a pharmacist communicated with each patient by either phone or e-mail every 2 weeks, making changes to their antihypertensive regimens as needed.

Patients in the intervention group had an average reduction in blood pressure of 14 mm Hg from baseline, and their blood pressure was much better controlled compared with the control groups, who were being passively monitored or were receiving usual care based on office blood pressure readings.

MEASURING ARTERIAL STIFFNESS TO ASSES RISK OF END-ORGAN DAMAGE

Mean arterial blood pressure, derived from the extremes of systolic and diastolic pressure as measured with a traditional sphygmomanometer, is a product of cardiac output and total peripheral vascular resistance. In contrast, central aortic blood pressure, the central augmentation index, and pulse wave velocity are measures derived from brachial blood pressure as well as arterial pulse wave tracings. They provide additional information on arterial stiffness and help stratify patients at increased cardiovascular risk.

The art of evaluating the arterial pulse wave with the fingertips while examining a patient and diagnosing various ailments was well known and practiced by ancient Greek and Chinese physicians. Although this was less recognized in Western medicine, it was the pulse wave recording on a sphygmograph that was used to measure human blood pressure in the 19th century.²³ In the early 20th century, this art was lost with the invention of the mercury sphygmomanometer.

Arterial stiffness indices—ie, central aortic blood pressure, the central augmentation index, and pulse wave velocity—can now be measured noninvasively and have been shown to correlate very well with measurements obtained via a central arterial catheter. In the past, the only way to measure central blood pressure was directly via a central arterial catheter. New devices now measure arterial stiffness indices indirectly by applanation tonometry and pulse wave analysis (reviewed by O’Rourke et al²⁵).

Several trials have shown that these arterial indices have a better prognostic value than the mean arterial pressure or the brachial pulse pressure. For example, the Baltimore Longitudinal Study of Aging²⁶ followed 100 normotensive individuals for 5 years and found that those with a higher pulse wave velocity had a greater chance of developing incident hypertension. Other studies showed that pulse wave velocity and other indices of arterial stiffness are associated with dysfunction of the microvasculature in the brain, with higher cardiovascular risk, and a higher risk of death.

A major limitation in measuring these arterial stiffness indices is that they are derived values and require measurement of brachial blood pressure in addition to the pulse wave tracing.

Recent hypertension guidelines^21,27,28 released during the past 2 years in Europe, Latin America, and Japan have recommended measurement of arterial stiffness as part of a comprehensive evaluation of patients with hypertension.

EXCITING TIMES IN HYPERTENSION

These are exciting times in the field of hypertension. With advances in technology, we have new devices and techniques that provide a closer view of the hemodynamic changes and blood pressures experienced by vital organs. In addition, we can now go beyond the physician’s office and evaluate blood pressure changes that occur during the course of a usual day in a patient’s life. This enables us to make better decisions in the management of their hypertension, embodying Dr. Harvey Cushing’s teaching that the physician’s obligation is to “view the man in his world.”²⁹

Hypertension is difficult to diagnose, and its treatment is difficult to monitor optimally on the basis of traditional office blood pressure measurements. To better protect our patients from the effects of undiagnosed or poorly controlled hypertension, we need to consider other options, such as ambulatory 24-hour blood pressure monitoring, automated measurement in the office, measurement in the patient’s home, and devices that analyze the peripheral pulse wave to estimate the central blood pressure and other indices of arterial stiffness.

MANUAL OFFICE MEASUREMENT HAS INHERENT LIMITATIONS

Office blood pressure measurements do provide enormous information about cardiovascular risk and the risk of death, as shown in epidemiologic studies. A meta-analysis¹ of 61 prospective observational studies that included more than 1 million patients showed that office blood pressure levels clearly correlate with increased risk of death from cardiovascular disease and stroke.

But blood pressure is a dynamic measure with inherent minute-to-minute variability, and measurement will not be accurate if the correct technique is not followed. Traditional office sphygmomanometry is a snapshot and does not accurately reflect a patient’s blood pressure in the real world and in real time.

Recently, unique patterns of blood pressure have been identified that may not be detected in the physician’s office. It is clear from several clinical trials that some patients’ blood pressure is transiently elevated in the first few minutes during office measurements (the “white coat effect”). In addition, when office measurements are compared with out-of-office measurements, several patterns of hypertension emerge that have prognostic value. These patterns are white coat hypertension, masked hypertension, nocturnal hypertension, and failure of the blood pressure to dip during sleep.

WHITE COAT EFFECT

The white coat effect is described as a transient elevation in office blood pressure caused by an alerting reaction when the pressure is measured by a physician or a nurse. It may last for several minutes. The magnitude of blood pressure elevation has been noted to be higher when measured by a physician than when measured by a nurse. Multiple blood pressure measurements taken over 5 to 10 minutes help eliminate the white coat effect. In a recent study,² 36% of patients with hypertension demonstrated the white coat effect.

In a study by Mancia et al,³ 46 patients underwent intra-arterial blood pressure monitoring for 2 days, during which time a physician or a nurse would check their blood pressure repeatedly over 10 minutes. This study found that most patients demonstrated the white coat effect: the blood pressure was higher in the first few measurements, but came down after 5 minutes. The white coat effect was as much as 22.6 ± 1.8 mm Hg when blood pressure was measured by a physician and was lower when measured by a nurse.

WHITE COAT HYPERTENSION

In contrast to the white coat effect, which is transient, white coat hypertension is defined as persistent elevation of office blood pressure measurements with normal blood pressure levels when measured outside the physician’s office. Depending on the population sampled, the prevalence of white coat hypertension ranges from 12% to 20%, but this is understandably difficult or almost impossible to detect with traditional office blood pressure measurements alone.^4–7

MASKED HYPERTENSION

Patients with normal blood pressure in the physician’s office but high blood pressure during daily life were found to have a higher risk of cardiovascular events. This condition is called masked hypertension.⁸ For clinicians, the danger lies in underestimating the patient’s risk of cardiovascular events and, thus, undertreating the hypertension. Preliminary data on masked hypertension show that the rates of end-organ damage and cardiovascular events are slightly higher in patients with masked hypertension than in patients with sustained hypertension.

NOCTURNAL HYPERTENSION

Elevated nighttime blood pressure (>125/75 mm Hg) is considered nocturnal hypertension and is generally considered a subgroup of masked hypertension.⁹

In the African American Study of Kidney Disease and Hypertension (AASK),^10,11 although most patients achieved their blood pressure goal during the trial, they were noted to have relentless progression of renal disease. On ambulatory 24-hour blood pressure monitoring during the cohort phase of the study,¹⁰ a high prevalence of elevated nighttime blood pressure (66%) was found. Further analysis showed that the elevated nighttime blood pressure was associated with worse hypertension-related end-organ damage. It is still unclear if lowering nighttime blood pressure improves clinical outcomes in this high-risk population.

DIPPING VS NONDIPPING

The mean blood pressure during sleep should normally decrease by 10% to 20% compared with daytime readings. “Nondipping,” ie, the lack of this nocturnal dip in blood pressure, carries a higher risk of death from cardiovascular causes, even if the person is otherwise normotensive.^12,13 Nondipping is commonly noted in African Americans, patients with diabetes, and those with chronic kidney disease.

A study by Lurbe et al¹⁴ of patients with type 1 diabetes mellitus who underwent ambulatory 24-hour blood pressure monitoring found that the onset of the nondipping phenomenon preceded microalbuminuria (a risk factor for kidney disease). Data from our institution¹⁵ showed that nondipping was associated with a greater decline in glomerular filtration rate when compared with dipping.

The lack of reproducibility of a person’s dipping status has been a barrier in relying on this as a prognostic measure. White and Larocca¹⁶ found that only about half of the patients who appeared to be nondippers on one 24-hour recording still were nondippers on a second recording 4 to 8 weeks later. Compared with nondipping, nocturnal hypertension is a more stable blood pressure pattern that is being increasingly recognized in patients undergoing 24-hour blood pressure monitoring.

AUTOMATIC BLOOD PRESSURE DEVICES

An automated in-office blood pressure measurement device is one way to minimize the white coat effect and obtain a more accurate blood pressure assessment. Devices such as BpTRU (BpTRU Medical Devices Ltd, Coquitlam, BC, Canada) are programmed to take a series of automatic, oscillometric readings at regular intervals while the patient is left alone in a quiet room. BpTRU has been validated in several clinical trials and has been shown to overcome the white coat effect to some extent. Myers et al¹⁷ compared 24-hour blood pressure readings with those obtained by a family physician, by a research technician, and by the BpTRU device and found that the BpTRU readings were much closer to the average of awake blood pressure readings on 24-hour blood pressure monitoring.

AMBULATORY 24-HOUR BLOOD PRESSURE MONITORING

• Presence or absence of the nocturnal dip (the normal 10% to 20% drop in blood pressure at night during sleep)
• Morning surge (which in some studies was associated with higher incidence of stroke)
• Supine hypertension and sudden fluctuations in blood pressure seen in patients with autonomic failure.

Studies have shown that basing antihypertensive therapy on ambulatory 24-hour blood pressure monitoring results in better control of hypertension and lowers the rate of cardiovascular events.^18,19

Perloff et al¹⁸ found that in patients whose hypertension was considered well controlled on the basis of office blood pressure measurements, those with higher blood pressures on ambulatory 24-hour monitoring had higher cardiovascular morbidity and mortality rates.

More recently, Clement et al¹⁹ showed that patients being treated for hypertension who have higher average ambulatory 24-hour blood pressures had a higher risk of cardiovascular events and cardiovascular death.

After following 790 patients for 3.7 years, Verdecchia et al²⁰ concluded that controlling hypertension on the basis of ambulatory 24-hour blood pressure readings rather than traditional office measurements lowered the risk of cardiovascular disease.

‘Normal’ blood pressure on ambulatory 24-hour monitoring

It should be noted that the normal average blood pressure on ambulatory 24-hour monitoring tends to be lower than that on traditional office readings. According to the 2007 European guidelines,²¹ an average 24-hour blood pressure above the range of 125/80 to 130/80 mm Hg is considered diagnostic of hypertension.

The bottom line on ambulatory 24-hour monitoring: Not perfect, but helpful

Ambulatory 24-hour blood pressure monitoring is not perfect. It interferes with the patient’s activities and with sleep, and this can affect the readings. It is also expensive, and Medicare and Medicaid cover it only if the patient is diagnosed with white coat hypertension, based on stringent criteria that include three elevated clinic blood pressure measurements and two normal out-of-clinic blood pressure measurements and no evidence of end-organ damage. Despite these issues, almost all national guidelines for the management of hypertension recommend ambulatory 24-hour blood pressure monitoring to improve cardiovascular risk prediction and to measure the variability in blood pressure levels.

USING THE INTERNET IN MANAGING HYPERTENSION

Green et al²² studied a new model of care using home blood pressure monitoring via the Internet, and provided feedback and intervention to the patient via a pharmacist to achieve blood pressure goals. Patients measured their blood pressure at home on at least 2 days a week (two measurements each time), using an automatic oscillometric monitor (Omron Hem-705-CP, Kyoto, Japan), and entered the results in an electronic medical record on the Internet. In the intervention group, a pharmacist communicated with each patient by either phone or e-mail every 2 weeks, making changes to their antihypertensive regimens as needed.

Patients in the intervention group had an average reduction in blood pressure of 14 mm Hg from baseline, and their blood pressure was much better controlled compared with the control groups, who were being passively monitored or were receiving usual care based on office blood pressure readings.

MEASURING ARTERIAL STIFFNESS TO ASSES RISK OF END-ORGAN DAMAGE

Mean arterial blood pressure, derived from the extremes of systolic and diastolic pressure as measured with a traditional sphygmomanometer, is a product of cardiac output and total peripheral vascular resistance. In contrast, central aortic blood pressure, the central augmentation index, and pulse wave velocity are measures derived from brachial blood pressure as well as arterial pulse wave tracings. They provide additional information on arterial stiffness and help stratify patients at increased cardiovascular risk.

The art of evaluating the arterial pulse wave with the fingertips while examining a patient and diagnosing various ailments was well known and practiced by ancient Greek and Chinese physicians. Although this was less recognized in Western medicine, it was the pulse wave recording on a sphygmograph that was used to measure human blood pressure in the 19th century.²³ In the early 20th century, this art was lost with the invention of the mercury sphygmomanometer.

Arterial stiffness indices—ie, central aortic blood pressure, the central augmentation index, and pulse wave velocity—can now be measured noninvasively and have been shown to correlate very well with measurements obtained via a central arterial catheter. In the past, the only way to measure central blood pressure was directly via a central arterial catheter. New devices now measure arterial stiffness indices indirectly by applanation tonometry and pulse wave analysis (reviewed by O’Rourke et al²⁵).

Several trials have shown that these arterial indices have a better prognostic value than the mean arterial pressure or the brachial pulse pressure. For example, the Baltimore Longitudinal Study of Aging²⁶ followed 100 normotensive individuals for 5 years and found that those with a higher pulse wave velocity had a greater chance of developing incident hypertension. Other studies showed that pulse wave velocity and other indices of arterial stiffness are associated with dysfunction of the microvasculature in the brain, with higher cardiovascular risk, and a higher risk of death.

A major limitation in measuring these arterial stiffness indices is that they are derived values and require measurement of brachial blood pressure in addition to the pulse wave tracing.

Recent hypertension guidelines^21,27,28 released during the past 2 years in Europe, Latin America, and Japan have recommended measurement of arterial stiffness as part of a comprehensive evaluation of patients with hypertension.

EXCITING TIMES IN HYPERTENSION

These are exciting times in the field of hypertension. With advances in technology, we have new devices and techniques that provide a closer view of the hemodynamic changes and blood pressures experienced by vital organs. In addition, we can now go beyond the physician’s office and evaluate blood pressure changes that occur during the course of a usual day in a patient’s life. This enables us to make better decisions in the management of their hypertension, embodying Dr. Harvey Cushing’s teaching that the physician’s obligation is to “view the man in his world.”²⁹