A 17‐year‐old female patient presented to the emergency department reporting having fever, sore throat, and pain with swallowing for several days. The result of her rapid strep screen was negative. She had an elevated white blood cell count, mildly elevated AST and ALT levels, and a positive result from a heterophile antibody test (BBL Monoslide). She was diagnosed with infectious mononucleosis. Given her inability to tolerate oral fluids, she was admitted to the hospital for intravenous hydration. After 3 days of receiving methylprednisolone intravenously, she had worsening throat pain, progressive neck swelling, difficulty handling her secretions, and new respiratory symptoms. During the examination, she was sitting upright in bed in moderate respiratory distress. She had kissing, exudative tonsils with palatal and uvular edema. Examination of her neck showed significantly enlarged anterior and posterior cervical lymph nodes without fluctuance. Her lung exam revealed subcostal retractions with transmitted upper airway sounds but good aeration. The edge of her liver and spleen tip were palpable.

Because of the rapid progression of symptoms while on medical therapy, computed tomography (CT) of the neck was performed. Sagittal reconstructions showed adenoidal hypertrophy compromising her nasopharynx, and massive tonsillar enlargement causing nearly complete obstruction of her oropharyngeal airway (Fig. 1), with airway narrowing to less than 2.5 mm in axial images. Bilateral low‐density lesions within the paratonsillar regions were suggestive of abscesses and retropharyngeal soft‐tissue swelling was consistent with phlegmon (Fig. 2). The patient was taken to the operating room for an emergent tonsillectomy. Bilateral peritonsillar abscesses were drained, pus was sent for culture, and her tonsils were excised. Cultures from the abscesses grew Streptococcus milleri. The patient was discharged home 2 days later to complete a 2‐week course of oral clindamycin.

Figure 1

Figure 2

Most patients with infectious mononucleosis (IM) have a benign, self‐limited course. However, a wide range of severe complications have been described including airway obstruction, splenic rupture, meningoencephalitis, Guillain‐Barr syndrome, peritonsillar abscess, and hemolytic anemia.1, 2 Upper‐airway obstruction results from lymphoid hyperplasia throughout Waldeyer's ring, with associated soft‐tissue edema. As many as 25% of patients hospitalized for IM will have some degree of airway obstruction.2, 3 Peritonsillar abscesses (PTAs) occur in approximately 1% of hospitalized patients with IM and may further obstruct the airway.4 Most commonly, peritonsillar abscesses are polymicrobial, having both aerobic and anaerobic bacteria. In a study of young adults with peritonsillar abscesses from all causes, Streptococcus pyogenes was the most common aerobe, found in nearly half of isolates; Streptococcus milleri, the bacterium isolated from our patient, was the second most common organism, found in approximately 25% of these abscesses.5 One prior case of airway obstruction from IM complicated by bilateral peritonsillar abscesses has been reported6; however, this patient was not reported to have concomitant retropharyngeal infection, as was noted in our patient.

Guidelines suggest that patients with mild, uncomplicated IM should be managed with supportive care alone; current recommendations are that steroids be prescribed only for specific complications of IM, including upper‐airway obstruction.7 Protocols for steroid regimens include initial prednisone doses ranging from 20 to 80 mg/day, with most advocating that they be tapered off over 1‐2 weeks.7, 8

Some of the controversy about the routine use of steroids in IM is related to concern for potential infectious complications associated with immunosuppression. In a small case series, Handler et al. proposed that there is an association between steroid therapy and the development of peritonsillar abscesses.9 However, this has not been tested in controlled trials, and the results of more recent studies do not support an increased likelihood of PTA in patients with infectious mononucleosis treated with corticosteroids.10, 11 Therefore, given that it has documented benefits and no proven adverse consequences, steroid therapy is uniformly recommended for patients with upper‐airway obstruction secondary to infectious mononucleosis. However, use of steroids also mandates careful monitoring for signs or symptoms suggestive of secondary bacterial infection.

For patients whose symptoms progress despite medical management including steroid therapy, surgical intervention may be required. Both tracheostomy and tonsillectomy during acute infection, sometimes referred to as hot tonsillectomy, have been reported as surgical options for airway obstruction in IM, the latter having emerged as the preferred treatment.3 Such treatment allows for drainage of any infectious collections, as well as removal of obstructing lymphoid tissue as indicated.

In conclusion, enlargement of tonsils and adenoids with associated edema in infectious mononucleosis can lead to upper‐airway obstruction. Patients with evidence of such obstruction should be treated with a tapering course of corticosteroids. Peritonsillar abscesses and deep neck infections are also severe complications of IM and can cause further respiratory compromise. In cases where medical therapy is not effective, such as with our patient, evaluation for peritonsillar abscess and need for possible acute tonsillectomy may be required.

A 17‐year‐old female patient presented to the emergency department reporting having fever, sore throat, and pain with swallowing for several days. The result of her rapid strep screen was negative. She had an elevated white blood cell count, mildly elevated AST and ALT levels, and a positive result from a heterophile antibody test (BBL Monoslide). She was diagnosed with infectious mononucleosis. Given her inability to tolerate oral fluids, she was admitted to the hospital for intravenous hydration. After 3 days of receiving methylprednisolone intravenously, she had worsening throat pain, progressive neck swelling, difficulty handling her secretions, and new respiratory symptoms. During the examination, she was sitting upright in bed in moderate respiratory distress. She had kissing, exudative tonsils with palatal and uvular edema. Examination of her neck showed significantly enlarged anterior and posterior cervical lymph nodes without fluctuance. Her lung exam revealed subcostal retractions with transmitted upper airway sounds but good aeration. The edge of her liver and spleen tip were palpable.

Because of the rapid progression of symptoms while on medical therapy, computed tomography (CT) of the neck was performed. Sagittal reconstructions showed adenoidal hypertrophy compromising her nasopharynx, and massive tonsillar enlargement causing nearly complete obstruction of her oropharyngeal airway (Fig. 1), with airway narrowing to less than 2.5 mm in axial images. Bilateral low‐density lesions within the paratonsillar regions were suggestive of abscesses and retropharyngeal soft‐tissue swelling was consistent with phlegmon (Fig. 2). The patient was taken to the operating room for an emergent tonsillectomy. Bilateral peritonsillar abscesses were drained, pus was sent for culture, and her tonsils were excised. Cultures from the abscesses grew Streptococcus milleri. The patient was discharged home 2 days later to complete a 2‐week course of oral clindamycin.

Figure 1

Figure 2

Most patients with infectious mononucleosis (IM) have a benign, self‐limited course. However, a wide range of severe complications have been described including airway obstruction, splenic rupture, meningoencephalitis, Guillain‐Barr syndrome, peritonsillar abscess, and hemolytic anemia.1, 2 Upper‐airway obstruction results from lymphoid hyperplasia throughout Waldeyer's ring, with associated soft‐tissue edema. As many as 25% of patients hospitalized for IM will have some degree of airway obstruction.2, 3 Peritonsillar abscesses (PTAs) occur in approximately 1% of hospitalized patients with IM and may further obstruct the airway.4 Most commonly, peritonsillar abscesses are polymicrobial, having both aerobic and anaerobic bacteria. In a study of young adults with peritonsillar abscesses from all causes, Streptococcus pyogenes was the most common aerobe, found in nearly half of isolates; Streptococcus milleri, the bacterium isolated from our patient, was the second most common organism, found in approximately 25% of these abscesses.5 One prior case of airway obstruction from IM complicated by bilateral peritonsillar abscesses has been reported6; however, this patient was not reported to have concomitant retropharyngeal infection, as was noted in our patient.

Guidelines suggest that patients with mild, uncomplicated IM should be managed with supportive care alone; current recommendations are that steroids be prescribed only for specific complications of IM, including upper‐airway obstruction.7 Protocols for steroid regimens include initial prednisone doses ranging from 20 to 80 mg/day, with most advocating that they be tapered off over 1‐2 weeks.7, 8

Some of the controversy about the routine use of steroids in IM is related to concern for potential infectious complications associated with immunosuppression. In a small case series, Handler et al. proposed that there is an association between steroid therapy and the development of peritonsillar abscesses.9 However, this has not been tested in controlled trials, and the results of more recent studies do not support an increased likelihood of PTA in patients with infectious mononucleosis treated with corticosteroids.10, 11 Therefore, given that it has documented benefits and no proven adverse consequences, steroid therapy is uniformly recommended for patients with upper‐airway obstruction secondary to infectious mononucleosis. However, use of steroids also mandates careful monitoring for signs or symptoms suggestive of secondary bacterial infection.

For patients whose symptoms progress despite medical management including steroid therapy, surgical intervention may be required. Both tracheostomy and tonsillectomy during acute infection, sometimes referred to as hot tonsillectomy, have been reported as surgical options for airway obstruction in IM, the latter having emerged as the preferred treatment.3 Such treatment allows for drainage of any infectious collections, as well as removal of obstructing lymphoid tissue as indicated.

In conclusion, enlargement of tonsils and adenoids with associated edema in infectious mononucleosis can lead to upper‐airway obstruction. Patients with evidence of such obstruction should be treated with a tapering course of corticosteroids. Peritonsillar abscesses and deep neck infections are also severe complications of IM and can cause further respiratory compromise. In cases where medical therapy is not effective, such as with our patient, evaluation for peritonsillar abscess and need for possible acute tonsillectomy may be required.

A 17‐year‐old female patient presented to the emergency department reporting having fever, sore throat, and pain with swallowing for several days. The result of her rapid strep screen was negative. She had an elevated white blood cell count, mildly elevated AST and ALT levels, and a positive result from a heterophile antibody test (BBL Monoslide). She was diagnosed with infectious mononucleosis. Given her inability to tolerate oral fluids, she was admitted to the hospital for intravenous hydration. After 3 days of receiving methylprednisolone intravenously, she had worsening throat pain, progressive neck swelling, difficulty handling her secretions, and new respiratory symptoms. During the examination, she was sitting upright in bed in moderate respiratory distress. She had kissing, exudative tonsils with palatal and uvular edema. Examination of her neck showed significantly enlarged anterior and posterior cervical lymph nodes without fluctuance. Her lung exam revealed subcostal retractions with transmitted upper airway sounds but good aeration. The edge of her liver and spleen tip were palpable.

Because of the rapid progression of symptoms while on medical therapy, computed tomography (CT) of the neck was performed. Sagittal reconstructions showed adenoidal hypertrophy compromising her nasopharynx, and massive tonsillar enlargement causing nearly complete obstruction of her oropharyngeal airway (Fig. 1), with airway narrowing to less than 2.5 mm in axial images. Bilateral low‐density lesions within the paratonsillar regions were suggestive of abscesses and retropharyngeal soft‐tissue swelling was consistent with phlegmon (Fig. 2). The patient was taken to the operating room for an emergent tonsillectomy. Bilateral peritonsillar abscesses were drained, pus was sent for culture, and her tonsils were excised. Cultures from the abscesses grew Streptococcus milleri. The patient was discharged home 2 days later to complete a 2‐week course of oral clindamycin.

Figure 1

Figure 2

Most patients with infectious mononucleosis (IM) have a benign, self‐limited course. However, a wide range of severe complications have been described including airway obstruction, splenic rupture, meningoencephalitis, Guillain‐Barr syndrome, peritonsillar abscess, and hemolytic anemia.1, 2 Upper‐airway obstruction results from lymphoid hyperplasia throughout Waldeyer's ring, with associated soft‐tissue edema. As many as 25% of patients hospitalized for IM will have some degree of airway obstruction.2, 3 Peritonsillar abscesses (PTAs) occur in approximately 1% of hospitalized patients with IM and may further obstruct the airway.4 Most commonly, peritonsillar abscesses are polymicrobial, having both aerobic and anaerobic bacteria. In a study of young adults with peritonsillar abscesses from all causes, Streptococcus pyogenes was the most common aerobe, found in nearly half of isolates; Streptococcus milleri, the bacterium isolated from our patient, was the second most common organism, found in approximately 25% of these abscesses.5 One prior case of airway obstruction from IM complicated by bilateral peritonsillar abscesses has been reported6; however, this patient was not reported to have concomitant retropharyngeal infection, as was noted in our patient.

Guidelines suggest that patients with mild, uncomplicated IM should be managed with supportive care alone; current recommendations are that steroids be prescribed only for specific complications of IM, including upper‐airway obstruction.7 Protocols for steroid regimens include initial prednisone doses ranging from 20 to 80 mg/day, with most advocating that they be tapered off over 1‐2 weeks.7, 8

Some of the controversy about the routine use of steroids in IM is related to concern for potential infectious complications associated with immunosuppression. In a small case series, Handler et al. proposed that there is an association between steroid therapy and the development of peritonsillar abscesses.9 However, this has not been tested in controlled trials, and the results of more recent studies do not support an increased likelihood of PTA in patients with infectious mononucleosis treated with corticosteroids.10, 11 Therefore, given that it has documented benefits and no proven adverse consequences, steroid therapy is uniformly recommended for patients with upper‐airway obstruction secondary to infectious mononucleosis. However, use of steroids also mandates careful monitoring for signs or symptoms suggestive of secondary bacterial infection.

For patients whose symptoms progress despite medical management including steroid therapy, surgical intervention may be required. Both tracheostomy and tonsillectomy during acute infection, sometimes referred to as hot tonsillectomy, have been reported as surgical options for airway obstruction in IM, the latter having emerged as the preferred treatment.3 Such treatment allows for drainage of any infectious collections, as well as removal of obstructing lymphoid tissue as indicated.

In conclusion, enlargement of tonsils and adenoids with associated edema in infectious mononucleosis can lead to upper‐airway obstruction. Patients with evidence of such obstruction should be treated with a tapering course of corticosteroids. Peritonsillar abscesses and deep neck infections are also severe complications of IM and can cause further respiratory compromise. In cases where medical therapy is not effective, such as with our patient, evaluation for peritonsillar abscess and need for possible acute tonsillectomy may be required.

Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

Glycemic control in hospitalized patients is receiving greater attention. The American Diabetes Association and the American College of Endocrinology recently issued a joint consensus statement on the need to implement tight blood glucose (BG) control in hospitalized patients.1, 2 The Joint Commission on Accreditation of Healthcare Organizations (JACHO) has developed an Advanced Inpatient Diabetes Care Certification Program for hospitals. However, despite all these efforts, it has been difficult to change how well glucose is controlled.3 A major hurdle in implementing glycemic control strategies is the prevalent fear of hypoglycemia among hospital staff. Although there are multiple protocols for insulin treatment,47 guidelines for the prevention and treatment of hypoglycemia are lacking. Once a hypoglycemic episode has occurred, reducing the dosage of diabetes medications may reduce subsequent episodes. This study was conducted to assess whether diabetes medications were decreased following an episode of hypoglycemia that led to treatment with intravenous (IV) dextrose.

METHODS

Data were collected by the Diabetes Subcommittee of the Pharmacy and Therapeutics Committee as part of a quality improvement initiative. Hypoglycemic episodes were identified by computerized orders for 50% dextrose solution. All orders in a 1‐month period (June 2006) were collected. Characteristics of patients experiencing these episodes were identified from the electronic medical records (EMR). The following data were collected: age, sex, history of diabetes, serum creatinine, diabetes medications at time of hypoglycemia, blood glucose at time of hypoglycemia, and all BG values in the 24 hours before hypoglycemia. BG values included those obtained in the laboratory as well as those obtained by bedside blood glucose testing. Treatment changes made right when the hypoglycemic episode occurred (immediate) and within 24 hours of the hypoglycemic episode (subsequent) were evaluated by 2 diabetes specialists, a board‐certified endocrinologist and a nurse‐practitioner working on the diabetes management service. The 2 practitioners regularly work together, but the data were evaluated independently. Because there are no specific guidelines, the appropriateness of change in treatment was based on general guidelines and experience. For example, if hypoglycemia developed while a patient was on insulin infusion therapy, it was appropriate to stop the drip when the episode of hypoglycemia occurred and to restart it at a lower rate according to the insulin infusion protocol. No subsequent changes would have been made in a situation such as this, and it was deemed appropriate. However, if a patient developed hypoglycemia while on subcutaneous (SC) insulin and then insulin was either completely discontinued or no change was made in subsequent orders, it was deemed inappropriate. The 2 diabetes specialists agreed in 87% of cases (kappa = 0.68, 95% CI 0.53‐0.84). In the 13% of cases in which the diabetes specialists had different opinions, they conferred to reach agreement. In patients with more than 1 episode, data related to the first episode were evaluated. Data are presented as means with SDs.

RESULTS

The EMR contained information on time of episode of hypoglycemia and medication changes for 52 patients, all of whom were in the study. Patient characteristics and mean blood glucose level are shown in Table 1. All patients were being treated with insulin when the episode of hypoglycemia occurred: 9 were on intravenous (IV) insulin alone, 3 on IV and subcutaneous (SC) insulin, 30 on scheduled SC insulin, and 10 on sliding‐scale SC insulin alone. Three patients were prescribed sulfonylurea drugs in addition to insulin. Insulin dosage of all 52 patients was held at the time of the hypoglycemic episode. Diabetes specialists agreed with this decision 100% of the time. Only 21 patients (40%) subsequently had reductions made in their treatment dosage, and diabetes specialists agreed with the changes made for 11 of these patients (52%). Thirty‐one patients (60%) had no changes made to their treatment, and diabetes specialists agreed with that decision for 10 of these patients (32%). When diabetes specialists disagreed with a decision, they would have decreased the insulin dose or changed the regimen in a different way. Details on the changes in treatment and whether diabetes specialists agreed with the changes are shown in Table 2. Twenty‐four hours after an episode of hypoglycemia, mean blood glucose of patients whose providers had made changes was 190.7 87.9 mg/dL and that of patients whose providers had not made changes was 122.6 43.2 mg/dL (P = NS). The mean BG of patients for whom the diabetologists agreed with the decision was 110.7 90.3 mg/dL, and that of patients for whom they disagreed with the decision was 139.7 42.8 mg/dL (P = NS).

DISCUSSION

These results suggest that treatment modification following an episode of hypoglycemia may be suboptimal. These data provide no information about the clinical circumstances leading to the choice of treatment with IV dextrose, as opposed to oral glucose or glucagon. Presumably, dextrose was chosen for many patients whom the physician considered to require the most urgent treatment. Appropriately, immediate treatment with insulin was held for all patients. On the other hand, 60% of the patients continued to receive the same insulin dose 24 hours after the hypoglycemic episode. Diabetes specialists judged continuation of the same dose as inappropriate in two thirds of the cases. Even when changes in treatment were made, those changes were judged suboptimal in half the cases. Blood glucose level 24 hours after an episode of hypoglycemia reflects these problems. These findings suggest that opportunities to prevent hypoglycemic episodes in the future are frequently missed. Lack of knowledge and/or guidelines for adjusting insulin dose following an episode of hypoglycemia seemed to have led to suboptimal changes for most patients.

Overall incidence of hypoglycemia (<60 mg/dL) among patients with diabetes admitted to a hospital has been reported to be 23%.8 In patients receiving continuous intravenous insulin infusion, the incidence of hypoglycemia has been variously reported as from 1.2% to 18.7%.9, 10 All insulin infusion protocols have guidelines for the immediate treatment of hypoglycemia and recommend steps to prevent further episodes. Although many hospitals have protocols for immediate action when hypoglycemia occurs (eg, hold insulin, give juice or dextrose), to our knowledge, no specific guidelines exist for adjustment of subcutaneous insulin following an episode of hypoglycemia. The vast majority of patients in a hospital are treated with SC insulin as opposed to IV insulin, and fear of hypoglycemia is a major barrier to intensified therapy. If widely applied, standardized protocols have the potential to be effective in preventing hypoglycemia.9

A limitation of our study was that it was a retrospective data analysis. We did not look at changes in clinical condition, in nutrition, and in other medications that might have led to the episode of hypoglycemia and affected the decision about which antidiabetic medications to treat with. Data on further episodes of hypoglycemia were also not available.

In conclusion, we have shown that treatment changes after an episode of hypoglycemia are chaotic and may be suboptimal. Standardized protocols may be helpful for making effective changes and potentially can reduce the risk of further episodes of hypoglycemia.

Approximately 10 million patients present to emergency departments each year with symptoms raising concern of thromboembolism (VTE).1 The current gold standard for diagnosis of VTE is pulmonary angiography.2 As this study is invasive, alternative imaging protocols have been sought. CTPA, when combined with measures of pretest probability, equals or surpasses the ability of pulmonary angiography to detect VTE and can improve the ability of clinicians to rule out VTE.38 In a study of 930 patients, application of clinical rules in addition to _D‐dimer testing decreased the number of CTPAs ordered by 50%.9 One of the most common clinical rule sets is the Wells Score, which relies on historical features related to the risk of DVT/VTE and physical examination findings.10, 11

Other institutions have demonstrated an increase in the number of CTPAs ordered and VTE diagnoses since the study became widely available.13 Based on the observation of an increasing number of CTPAs ordered at our institution without an increase in the number of VTEs diagnosed, we aimed to ascertain the physician ordering practices for CTPA. We hypothesized that CTPAs were ordered at a greater frequency in a low‐risk population because an institutional clinical algorithm was lacking.

METHODS

Charts of all patients aged 18‐100 with CTPA ordered to rule out acute VTE were retrospectively examined. A Simplified Wells Score was applied using only the information available to the ordering physician at the time the CTPA was performed. Patients were stratified by their Simplified Wells Score to low (0‐1 points), intermediate (2‐6 points), or high (>6 points) pretest clinical probability. A _D‐dimer value, if ordered, was used to further stratify patients based on a positive or negative result. The official radiologic report of the CTPA was used to determine the rate of VTE diagnosis for the study population.

RESULTS

Three hundred and ninety‐four patients were referred for CTPA (Fig. 1). Two hundred and seventy‐nine had adequate clinical data to calculate a Simplified Wells Score and were included in the study. Of the 279 studies included, 75% were ordered through the emergency department and 25% from inpatient services (Table 1). The study patients were stratified according to the Simplified Wells criteria: 184 patients (66%) had low clinical probability, 91 (33%) had intermediate clinical probability, and 4 (1%) had high clinical probability. Nineteen (7%) patients had a history of DVT or VTE, and 28 (10%) had a history of active cancer at the time of their CTPA. One hundred and twenty‐five of the 279 patients had a _D‐dimer performed (Fig. 2). One hundred and eight were positive, and 17 were negative. Of the 17 patients who had a negative _D‐dimer and underwent CTPA testing, none were diagnosed with VTE. Eighty‐three low‐clinical‐probability patients underwent CTPA without _D‐dimer testing, 4 of whom were diagnosed with VTE.

Figure 1

Figure 2

There were 20 positive CTPAs in the study group (Fig. 3). Review of the records for 3 months after the study of patients whose CTPA was negative disclosed no diagnoses of VTE by other modalities. VTE was diagnosed in 4% of patients in the low‐clinical‐probability group, 12% in the intermediate‐clinical‐probability group, and 25% in the high‐clinical‐probability group. The overall positive CTPA rate was 7.2%.

Figure 3

DISCUSSION

Many studies have examined the application of clinical rule sets in addition to D‐dimer testing and CTPA to exclude acute VTE.39 Most of these studies have shown that the use of an algorithm is safe and frequently reduces referral for CTPA in low‐clinical‐probability patients. However, others have noted that some physicians do not routinely use validated algorithms when making decisions related to patient evaluation.13 Our rate of positive CTPA was low compared with rates reported in the literature.3, 14 We believe the most likely explanation is the large number of low‐clinical‐probability patients who underwent CTPA, possibly because providers do not routinely use a validated clinical algorithm.

When our patient population was risk stratified by Simplified Wells criteria and compared with similar data from published studies, we had a much higher proportion of patients classified as low clinical probability.7, 8, 15 The low‐clinical‐probability group's mean Simplified Wells Score was 0.71; one‐third had a Simplified Wells Score of 0. This reflects a low‐risk population for VTE, supported by the low prevalence of prior DVT/VTE and active cancer in our population.4, 10 The rationale for referring patients with so few risk factors for CTPA is unclear. It is possible that providers used CTPA to evaluate symptoms not clearly explained and obtained the study to look for other diagnoses in addition to VTE. By not applying a clinical algorithm, very‐low‐risk patients underwent CTPA, increasing the number of negative studies and decreasing the overall positive rate.

Not using a clinical algorithm also resulted in indiscriminate _D‐dimer testing. There were 83 patients risk‐stratified as low clinical probability who did not have a _D‐dimer prior to undergoing CTPA. Some of these patients may well have had a negative _D‐dimer, requiring no further workup to rule out VTE. Seventeen patients had a negative _D‐dimer and still underwent CTPA; all these patients were negative for VTE. These aberrations likely occurred from unfamiliarity with use of the _D‐dimer test or doubts about its ability to reliably exclude VTE. Appropriate application of _D‐dimer testing could have decreased the number of CTPAs ordered and increased our overall rate of positive VTE diagnosis.

Perrier et al., Brown et al., and Kelly and Wells all describe different methods of introducing clinical algorithms to aid the diagnosis of VTE.46, 9 All agree that patients should be risk stratified by pretest clinical probability, and low‐probability patients should undergo intermediate testing with _D‐dimer prior to CTPA. Implementation of a similar clinical algorithm at our facility would likely decrease the number of CTPAs ordered. If all patients presenting at our facility with signs and symptoms raising concern for VTE were first risk‐stratified by pretest clinical probability, and all low‐probability patients underwent highly‐sensitive _D‐dimer testing as an initial step, fewer CTPAs would be performed on low‐probability patients. The largest group of patients in our study were low probability; therefore, decreasing CTPA in this group could have a significant effect on our institution.

The retrospective nature of our study resulted in the following limitations. It is impossible to determine how the ordering provider viewed the patient's pretest probability. In most of the medical records, a pretest clinical probability was not documented. We attempted to validate the ordering provider's decision by being as generous as possible in applying points to the Wells Score. For example, if a patient had a remote history of cancer and the ordering provider documented this as a risk factor for VTE, the point value for cancer was given even though the Wells Score has a much narrower definition of this category.10 This practice favors assigning patients a potentially higher clinical probability and may have increased the number of patients designated as intermediate and high clinical probability in our study.

Our hospital primarily relies on CTPA with lower extremity venogram as the diagnostic test for VTE. Indeterminate tests may have occurred and thus falsely lowered the number of VTEs diagnosed. However, no patient with a negative CTPA was diagnosed with VTE by any modality in the 3 months after their initial study at our institution; a diagnosis of VTE could have been made at another hospital. The Simplified Wells Score uses both objective and subjective components to arrive at a point total. Our results might be different if newer algorithms, such as the Revised Geneva Score,16 which relies only on objective measurements, had been used.

CONCLUSIONS

The reliance on CTPA alone to exclude a potentially life‐threatening illness without additional risk stratification or clinical information leads to overuse of this test in patients with very low to no clinical risk for VTE and a low rate of diagnosed VTE. Implementation of a clinical algorithm for the diagnosis of suspected VTE may eliminate the need for many CTPAs, improving the yield of this test without compromising patient safety, especially at institutions with a low prevalence of PE.

Approximately 10 million patients present to emergency departments each year with symptoms raising concern of thromboembolism (VTE).1 The current gold standard for diagnosis of VTE is pulmonary angiography.2 As this study is invasive, alternative imaging protocols have been sought. CTPA, when combined with measures of pretest probability, equals or surpasses the ability of pulmonary angiography to detect VTE and can improve the ability of clinicians to rule out VTE.38 In a study of 930 patients, application of clinical rules in addition to _D‐dimer testing decreased the number of CTPAs ordered by 50%.9 One of the most common clinical rule sets is the Wells Score, which relies on historical features related to the risk of DVT/VTE and physical examination findings.10, 11

Other institutions have demonstrated an increase in the number of CTPAs ordered and VTE diagnoses since the study became widely available.13 Based on the observation of an increasing number of CTPAs ordered at our institution without an increase in the number of VTEs diagnosed, we aimed to ascertain the physician ordering practices for CTPA. We hypothesized that CTPAs were ordered at a greater frequency in a low‐risk population because an institutional clinical algorithm was lacking.

METHODS

Charts of all patients aged 18‐100 with CTPA ordered to rule out acute VTE were retrospectively examined. A Simplified Wells Score was applied using only the information available to the ordering physician at the time the CTPA was performed. Patients were stratified by their Simplified Wells Score to low (0‐1 points), intermediate (2‐6 points), or high (>6 points) pretest clinical probability. A _D‐dimer value, if ordered, was used to further stratify patients based on a positive or negative result. The official radiologic report of the CTPA was used to determine the rate of VTE diagnosis for the study population.

RESULTS

Three hundred and ninety‐four patients were referred for CTPA (Fig. 1). Two hundred and seventy‐nine had adequate clinical data to calculate a Simplified Wells Score and were included in the study. Of the 279 studies included, 75% were ordered through the emergency department and 25% from inpatient services (Table 1). The study patients were stratified according to the Simplified Wells criteria: 184 patients (66%) had low clinical probability, 91 (33%) had intermediate clinical probability, and 4 (1%) had high clinical probability. Nineteen (7%) patients had a history of DVT or VTE, and 28 (10%) had a history of active cancer at the time of their CTPA. One hundred and twenty‐five of the 279 patients had a _D‐dimer performed (Fig. 2). One hundred and eight were positive, and 17 were negative. Of the 17 patients who had a negative _D‐dimer and underwent CTPA testing, none were diagnosed with VTE. Eighty‐three low‐clinical‐probability patients underwent CTPA without _D‐dimer testing, 4 of whom were diagnosed with VTE.

Figure 1

Figure 2

There were 20 positive CTPAs in the study group (Fig. 3). Review of the records for 3 months after the study of patients whose CTPA was negative disclosed no diagnoses of VTE by other modalities. VTE was diagnosed in 4% of patients in the low‐clinical‐probability group, 12% in the intermediate‐clinical‐probability group, and 25% in the high‐clinical‐probability group. The overall positive CTPA rate was 7.2%.

Figure 3

DISCUSSION

Many studies have examined the application of clinical rule sets in addition to D‐dimer testing and CTPA to exclude acute VTE.39 Most of these studies have shown that the use of an algorithm is safe and frequently reduces referral for CTPA in low‐clinical‐probability patients. However, others have noted that some physicians do not routinely use validated algorithms when making decisions related to patient evaluation.13 Our rate of positive CTPA was low compared with rates reported in the literature.3, 14 We believe the most likely explanation is the large number of low‐clinical‐probability patients who underwent CTPA, possibly because providers do not routinely use a validated clinical algorithm.

When our patient population was risk stratified by Simplified Wells criteria and compared with similar data from published studies, we had a much higher proportion of patients classified as low clinical probability.7, 8, 15 The low‐clinical‐probability group's mean Simplified Wells Score was 0.71; one‐third had a Simplified Wells Score of 0. This reflects a low‐risk population for VTE, supported by the low prevalence of prior DVT/VTE and active cancer in our population.4, 10 The rationale for referring patients with so few risk factors for CTPA is unclear. It is possible that providers used CTPA to evaluate symptoms not clearly explained and obtained the study to look for other diagnoses in addition to VTE. By not applying a clinical algorithm, very‐low‐risk patients underwent CTPA, increasing the number of negative studies and decreasing the overall positive rate.

Not using a clinical algorithm also resulted in indiscriminate _D‐dimer testing. There were 83 patients risk‐stratified as low clinical probability who did not have a _D‐dimer prior to undergoing CTPA. Some of these patients may well have had a negative _D‐dimer, requiring no further workup to rule out VTE. Seventeen patients had a negative _D‐dimer and still underwent CTPA; all these patients were negative for VTE. These aberrations likely occurred from unfamiliarity with use of the _D‐dimer test or doubts about its ability to reliably exclude VTE. Appropriate application of _D‐dimer testing could have decreased the number of CTPAs ordered and increased our overall rate of positive VTE diagnosis.

Perrier et al., Brown et al., and Kelly and Wells all describe different methods of introducing clinical algorithms to aid the diagnosis of VTE.46, 9 All agree that patients should be risk stratified by pretest clinical probability, and low‐probability patients should undergo intermediate testing with _D‐dimer prior to CTPA. Implementation of a similar clinical algorithm at our facility would likely decrease the number of CTPAs ordered. If all patients presenting at our facility with signs and symptoms raising concern for VTE were first risk‐stratified by pretest clinical probability, and all low‐probability patients underwent highly‐sensitive _D‐dimer testing as an initial step, fewer CTPAs would be performed on low‐probability patients. The largest group of patients in our study were low probability; therefore, decreasing CTPA in this group could have a significant effect on our institution.

The retrospective nature of our study resulted in the following limitations. It is impossible to determine how the ordering provider viewed the patient's pretest probability. In most of the medical records, a pretest clinical probability was not documented. We attempted to validate the ordering provider's decision by being as generous as possible in applying points to the Wells Score. For example, if a patient had a remote history of cancer and the ordering provider documented this as a risk factor for VTE, the point value for cancer was given even though the Wells Score has a much narrower definition of this category.10 This practice favors assigning patients a potentially higher clinical probability and may have increased the number of patients designated as intermediate and high clinical probability in our study.

Our hospital primarily relies on CTPA with lower extremity venogram as the diagnostic test for VTE. Indeterminate tests may have occurred and thus falsely lowered the number of VTEs diagnosed. However, no patient with a negative CTPA was diagnosed with VTE by any modality in the 3 months after their initial study at our institution; a diagnosis of VTE could have been made at another hospital. The Simplified Wells Score uses both objective and subjective components to arrive at a point total. Our results might be different if newer algorithms, such as the Revised Geneva Score,16 which relies only on objective measurements, had been used.

CONCLUSIONS

The reliance on CTPA alone to exclude a potentially life‐threatening illness without additional risk stratification or clinical information leads to overuse of this test in patients with very low to no clinical risk for VTE and a low rate of diagnosed VTE. Implementation of a clinical algorithm for the diagnosis of suspected VTE may eliminate the need for many CTPAs, improving the yield of this test without compromising patient safety, especially at institutions with a low prevalence of PE.

Approximately 10 million patients present to emergency departments each year with symptoms raising concern of thromboembolism (VTE).1 The current gold standard for diagnosis of VTE is pulmonary angiography.2 As this study is invasive, alternative imaging protocols have been sought. CTPA, when combined with measures of pretest probability, equals or surpasses the ability of pulmonary angiography to detect VTE and can improve the ability of clinicians to rule out VTE.38 In a study of 930 patients, application of clinical rules in addition to _D‐dimer testing decreased the number of CTPAs ordered by 50%.9 One of the most common clinical rule sets is the Wells Score, which relies on historical features related to the risk of DVT/VTE and physical examination findings.10, 11

Other institutions have demonstrated an increase in the number of CTPAs ordered and VTE diagnoses since the study became widely available.13 Based on the observation of an increasing number of CTPAs ordered at our institution without an increase in the number of VTEs diagnosed, we aimed to ascertain the physician ordering practices for CTPA. We hypothesized that CTPAs were ordered at a greater frequency in a low‐risk population because an institutional clinical algorithm was lacking.

METHODS

Charts of all patients aged 18‐100 with CTPA ordered to rule out acute VTE were retrospectively examined. A Simplified Wells Score was applied using only the information available to the ordering physician at the time the CTPA was performed. Patients were stratified by their Simplified Wells Score to low (0‐1 points), intermediate (2‐6 points), or high (>6 points) pretest clinical probability. A _D‐dimer value, if ordered, was used to further stratify patients based on a positive or negative result. The official radiologic report of the CTPA was used to determine the rate of VTE diagnosis for the study population.

RESULTS

Three hundred and ninety‐four patients were referred for CTPA (Fig. 1). Two hundred and seventy‐nine had adequate clinical data to calculate a Simplified Wells Score and were included in the study. Of the 279 studies included, 75% were ordered through the emergency department and 25% from inpatient services (Table 1). The study patients were stratified according to the Simplified Wells criteria: 184 patients (66%) had low clinical probability, 91 (33%) had intermediate clinical probability, and 4 (1%) had high clinical probability. Nineteen (7%) patients had a history of DVT or VTE, and 28 (10%) had a history of active cancer at the time of their CTPA. One hundred and twenty‐five of the 279 patients had a _D‐dimer performed (Fig. 2). One hundred and eight were positive, and 17 were negative. Of the 17 patients who had a negative _D‐dimer and underwent CTPA testing, none were diagnosed with VTE. Eighty‐three low‐clinical‐probability patients underwent CTPA without _D‐dimer testing, 4 of whom were diagnosed with VTE.

Figure 1

Figure 2

There were 20 positive CTPAs in the study group (Fig. 3). Review of the records for 3 months after the study of patients whose CTPA was negative disclosed no diagnoses of VTE by other modalities. VTE was diagnosed in 4% of patients in the low‐clinical‐probability group, 12% in the intermediate‐clinical‐probability group, and 25% in the high‐clinical‐probability group. The overall positive CTPA rate was 7.2%.

Figure 3

DISCUSSION

Many studies have examined the application of clinical rule sets in addition to D‐dimer testing and CTPA to exclude acute VTE.39 Most of these studies have shown that the use of an algorithm is safe and frequently reduces referral for CTPA in low‐clinical‐probability patients. However, others have noted that some physicians do not routinely use validated algorithms when making decisions related to patient evaluation.13 Our rate of positive CTPA was low compared with rates reported in the literature.3, 14 We believe the most likely explanation is the large number of low‐clinical‐probability patients who underwent CTPA, possibly because providers do not routinely use a validated clinical algorithm.

When our patient population was risk stratified by Simplified Wells criteria and compared with similar data from published studies, we had a much higher proportion of patients classified as low clinical probability.7, 8, 15 The low‐clinical‐probability group's mean Simplified Wells Score was 0.71; one‐third had a Simplified Wells Score of 0. This reflects a low‐risk population for VTE, supported by the low prevalence of prior DVT/VTE and active cancer in our population.4, 10 The rationale for referring patients with so few risk factors for CTPA is unclear. It is possible that providers used CTPA to evaluate symptoms not clearly explained and obtained the study to look for other diagnoses in addition to VTE. By not applying a clinical algorithm, very‐low‐risk patients underwent CTPA, increasing the number of negative studies and decreasing the overall positive rate.

Not using a clinical algorithm also resulted in indiscriminate _D‐dimer testing. There were 83 patients risk‐stratified as low clinical probability who did not have a _D‐dimer prior to undergoing CTPA. Some of these patients may well have had a negative _D‐dimer, requiring no further workup to rule out VTE. Seventeen patients had a negative _D‐dimer and still underwent CTPA; all these patients were negative for VTE. These aberrations likely occurred from unfamiliarity with use of the _D‐dimer test or doubts about its ability to reliably exclude VTE. Appropriate application of _D‐dimer testing could have decreased the number of CTPAs ordered and increased our overall rate of positive VTE diagnosis.

Perrier et al., Brown et al., and Kelly and Wells all describe different methods of introducing clinical algorithms to aid the diagnosis of VTE.46, 9 All agree that patients should be risk stratified by pretest clinical probability, and low‐probability patients should undergo intermediate testing with _D‐dimer prior to CTPA. Implementation of a similar clinical algorithm at our facility would likely decrease the number of CTPAs ordered. If all patients presenting at our facility with signs and symptoms raising concern for VTE were first risk‐stratified by pretest clinical probability, and all low‐probability patients underwent highly‐sensitive _D‐dimer testing as an initial step, fewer CTPAs would be performed on low‐probability patients. The largest group of patients in our study were low probability; therefore, decreasing CTPA in this group could have a significant effect on our institution.

The retrospective nature of our study resulted in the following limitations. It is impossible to determine how the ordering provider viewed the patient's pretest probability. In most of the medical records, a pretest clinical probability was not documented. We attempted to validate the ordering provider's decision by being as generous as possible in applying points to the Wells Score. For example, if a patient had a remote history of cancer and the ordering provider documented this as a risk factor for VTE, the point value for cancer was given even though the Wells Score has a much narrower definition of this category.10 This practice favors assigning patients a potentially higher clinical probability and may have increased the number of patients designated as intermediate and high clinical probability in our study.

Our hospital primarily relies on CTPA with lower extremity venogram as the diagnostic test for VTE. Indeterminate tests may have occurred and thus falsely lowered the number of VTEs diagnosed. However, no patient with a negative CTPA was diagnosed with VTE by any modality in the 3 months after their initial study at our institution; a diagnosis of VTE could have been made at another hospital. The Simplified Wells Score uses both objective and subjective components to arrive at a point total. Our results might be different if newer algorithms, such as the Revised Geneva Score,16 which relies only on objective measurements, had been used.

CONCLUSIONS

The reliance on CTPA alone to exclude a potentially life‐threatening illness without additional risk stratification or clinical information leads to overuse of this test in patients with very low to no clinical risk for VTE and a low rate of diagnosed VTE. Implementation of a clinical algorithm for the diagnosis of suspected VTE may eliminate the need for many CTPAs, improving the yield of this test without compromising patient safety, especially at institutions with a low prevalence of PE.

Vascular surgery has higher morbidity and mortality than other noncardiac surgeries. Despite the identification of vascular surgery as higher risk, 30‐day mortality for this surgery has remained at 3%10%. Few studies have examined longer‐term outcomes, but higher mortality rates have been reported, for example, 10%30% 6 months after surgery, 20%40% 1 year after surgery, and 30%50% 5 years after surgery.15 Postoperative adverse events have been found to be highly correlated with perioperative ischemia and infarction.68 Perioperative beta‐blockers have been widely studied and have been shown to benefit patients undergoing noncardiac surgery generally and vascular surgery specifically.9, 10 However, 2 recent trials of perioperative beta‐blockers in noncardiac and vascular surgery patients failed to show an association with 18‐month and 30‐day postoperative morbidity and mortality, respectively.11, 12 In addition, the authors of a recent meta‐analysis of perioperative beta‐blockers suggested more studies were needed.13 Furthermore, there have been promising new data on the use of perioperative statins.1418 Finally, as a recent clinical trial of revascularization before vascular surgery did not demonstrate an advantage over medical management, the identification of which perioperative medicines improve postoperative outcomes and in what combinations becomes even more important.19 We sought to ascertain if the ambulatory use of statins and/or beta‐blockers within 30 days of surgery was associated with a reduction in long‐term mortality.

METHODS

RESULTS

Univariate Survival Analysis

Univariate Cox regression analysis revealed a strong effect of the composite RCRI, which was predictive of mortality in a linear fashion over the course of the study compared with an RCRI of 0 (Table 1). Univariate analysis showed significant associations with decreased mortality for statins (hazard ratio [HR] = 0.66 [95% CI 0.580.75], P < .0001) and beta‐blockers (HR = 0.74 [95% CI 0.660.84], P = .0001); see Table 1. Of note, compared with that in 1998, mortality did not change for all the years for which data were complete. In addition, compared with taking neither study drug, taking a statin only, a beta‐blocker only, or both was associated with decreased mortality (P = .0002, P = .0079, and P < .0001, respectively; Fig. 1).

Figure 1

Propensity Score Analysis for Single Study Drug

There were significant differences in demographic and clinical characteristics between statin‐users versus statin nonusers, and between beta‐blocker users versus beta‐blocker nonusers. These differences became insignificant after the propensity score adjustment, with the exception of hyperlipidemia for statins, P = .02, which was added to the model as a confounder (Table 2). The distribution of the propensity scores was similar for study drug users and nonusers within each stratum. The association with decreased mortality remained significant after adjusting for propensity score (for statins, HR = 0.78 [95% CI 0.670.92, P = .0050], number needed to treat [NNT] = 22; for beta‐blockers HR = 0.84 [95% CI 0.730.96, P = .0103], NNT = 30; Fig. 2).

Figure 2

DISCUSSION

In this retrospective observational study we found that after vascular surgery the use of propensity‐adjusted statins compared with no use of statins reduced long‐term mortality over the study period by 22%, with a number needed to treat of 22, and the use of propensity‐adjusted beta‐blockers compared with no use also reduced long‐term mortality, by 16%, with a number needed to treat of 30. There were no statistically significant differences between outcomes of statin users and beta‐blocker users. In addition, using a propensity‐adjusted combination of statin and beta‐blockers compared with using neither decreased mortality overall by 44%, with a number needed to treat of 9. We focused on the use of outpatient drugs 30 days before or after surgery, as the timing of potentially beneficial medications has not been clearly established. Over time, more patients originally categorized as not taking a study drug began taking one, so that by 2 years after surgery, 58% of the patients were taking a statin, and 67% were taking a beta‐blocker, compared with 44% and 53%, respectively, of the study cohort initially. This would have made it more difficult to demonstrate a difference between these 2 groups. As more patients ended up taking the study drugs over time than the originally identified study drug users, and a mortality difference was still demonstrated, there may be an increased advantage in taking the study drugs around the time of surgery. As our focus was on long‐term postoperative mortality, which has not commonly been studied according to the literature, we preferred to also focus on long‐term, chronic ambulatory use of the study drugs. We did perform a subcohort analysis of the timing of study drug use. This confirmed that this cohort predominately comprised long‐term users of the study drugs who took the drug both before and after surgery. This study was not powered to comment on 30‐day mortality.

Perioperative beta‐blockers have been shown in retrospective cohort studies, case‐control studies, randomized clinical trials, meta‐analyses, and systematic reviews to decrease mortality and morbidity after noncardiac surgery. Although recent studies have not shown a benefit for more moderate‐ to low‐risk subjects,11, 12 perioperative beta‐blockers are still considered an indicator of health care quality in the United States.25 At present, perioperative beta‐blockers have an ACC/AHA class I indication (should be administered; Evidence level C) for patients undergoing vascular surgery with a positive stress test, and class IIa indication (reasonable to administer; Evidence level B) for vascular surgery patients with coronary heart disease or multiple clinical risk factors.26 A recent observational study in noncardiac surgery patients demonstrated perioperative beta‐blockers may be most helpful to prevent in‐hospital death after surgery of patients with an RCRI 2 and may be unhelpful or harmful for patients with an RCRI 1.27 Our univariate RCRI findings did not agree, as we found all patients whatever their level of risk benefited from perioperative use of beta‐blockers, alone or in combination. Our study population was older, had a higher RCRI, and underwent comparatively higher‐risk surgery, we were investigating longer‐term outcome, and we concentrated on ambulatory use of beta‐blockers, which may have contributed to the divergence in findings. Our propensity‐adjusted RCRI analysis did not show beta‐blockers associated with any change in mortality at any patient risk level. This may be, in part, because of the reduced number of patients in the RCRI strata. RCRI stratum‐specific analysis is limited by the number of patients and deaths in each RCRI stratum. For example, the power to detect a 2‐year difference of 10% (or 5%) between statin users and nonusers is approximately 99% (66%), 99% (59%), 92% (42%), and 61% (23%) for RCRI = 0, 1, 2, and 3, respectively.

Case‐control and retrospective cohort studies and one randomized clinical trial have shown perioperative statins to decrease either short‐term cardiovascular morbidity or mortality up to 30 days after surgery, and a limited number of retrospective cohort studies have shown reduced mortality for longer‐term follow‐up.1418, 28 There was one previous preliminary study of vascular surgery patients that demonstrated an additive benefit of using statins and beta‐blockers up to 30 days after surgery. This additive effect was only observed in patients with an RCRI 3.29 The results of our longer‐term follow‐up study of a larger cohort did not agree. Compared with patients who did not take a statin or a beta‐blocker, those patients who took both study drugs decreased their relative risk of mortality by approximately 36% in propensity‐ adjusted analysis and by about 50% in univariate analysis, regardless of patient‐specific risk level. For example, in the propensity‐adjusted analysis, the healthiest patients with an RCRI of 0 who took both study drugs had lower mortality than patients who took neither study drug, 8% versus 14%, a 38% relative reduction in mortality, with a number needed to treat of 20 (P = .0184).

In addition, the use of the RCRI for the first time highlighted the divergent long‐term mortality rates for patient‐specific risk levels and the striking long‐term associations of the perioperative use of ambulatory statins, beta‐blockers, and both drugs in combination with improved long‐term mortality. The long‐term use of the study drugs may indeed help all patients with atherosclerotic vascular disease, regardless of surgery. However, vascular surgery presents an opportunity for medical intervention, and our results are most applicable for these patients. In addition, the perioperative state has a unique physiology of acute and intense inflammation and thrombosis. Beta‐blockers and statins have antiadrenergic, anti‐inflammatory, and antithrombotic properties that may be beneficial during this high‐risk state.

Our findings should be viewed with some caution. The use of ICD‐9 codes and demographic data is dependent on the documentation and coding of comorbidities in the medical record and database. The use of statins and beta‐blockers was not random, and patients who took statins and beta‐blockers were different than those who did not. We used rigorous propensity and multivariate analysis, including controlling for clonidine, which has been shown to decrease death after vascular surgery.30 We also controlled for serum albumin level, which has been shown to be a leading predictor of postoperative death.31 We further separately stratified patients by RCRI, as this was a powerful predictor of death in the univariate analysis, but because of the retrospective nature of the study, unmeasured confounders may exist. Only 1% of the study patients were women, which is a limitation of the study. This administrative database is also limited by not having information on tobacco use for 47% of the patients and by not knowing ethnicity for 80% of the patients.

The use of perioperative statins and beta‐blockers used alone or in combination was associated with a reduction in long‐term mortality for vascular surgery patients, and combination use benefited patients at all levels of risk. Higher‐risk patients benefited most by taking both study drugs. These findings extend prior data, add to the natural history of long‐term postoperative outcomes, and also support clinical trials that would evaluate the prospective use of both these medications in vascular surgery patients with attention to patient‐specific risk level. Until the results of 2 randomized controlled trials become available, which may further clarify the use of perioperative statins and beta‐blockers in noncardiac, and noncardiac vascular surgery,13, 32 the use of statins and beta‐blockers should be considered for all patients undergoing vascular surgery. In addition, long‐term use of statins and beta‐blockers for all patients with atherosclerotic vascular disease should be considered.33

Vascular surgery has higher morbidity and mortality than other noncardiac surgeries. Despite the identification of vascular surgery as higher risk, 30‐day mortality for this surgery has remained at 3%10%. Few studies have examined longer‐term outcomes, but higher mortality rates have been reported, for example, 10%30% 6 months after surgery, 20%40% 1 year after surgery, and 30%50% 5 years after surgery.15 Postoperative adverse events have been found to be highly correlated with perioperative ischemia and infarction.68 Perioperative beta‐blockers have been widely studied and have been shown to benefit patients undergoing noncardiac surgery generally and vascular surgery specifically.9, 10 However, 2 recent trials of perioperative beta‐blockers in noncardiac and vascular surgery patients failed to show an association with 18‐month and 30‐day postoperative morbidity and mortality, respectively.11, 12 In addition, the authors of a recent meta‐analysis of perioperative beta‐blockers suggested more studies were needed.13 Furthermore, there have been promising new data on the use of perioperative statins.1418 Finally, as a recent clinical trial of revascularization before vascular surgery did not demonstrate an advantage over medical management, the identification of which perioperative medicines improve postoperative outcomes and in what combinations becomes even more important.19 We sought to ascertain if the ambulatory use of statins and/or beta‐blockers within 30 days of surgery was associated with a reduction in long‐term mortality.

METHODS

RESULTS

Univariate Survival Analysis

Univariate Cox regression analysis revealed a strong effect of the composite RCRI, which was predictive of mortality in a linear fashion over the course of the study compared with an RCRI of 0 (Table 1). Univariate analysis showed significant associations with decreased mortality for statins (hazard ratio [HR] = 0.66 [95% CI 0.580.75], P < .0001) and beta‐blockers (HR = 0.74 [95% CI 0.660.84], P = .0001); see Table 1. Of note, compared with that in 1998, mortality did not change for all the years for which data were complete. In addition, compared with taking neither study drug, taking a statin only, a beta‐blocker only, or both was associated with decreased mortality (P = .0002, P = .0079, and P < .0001, respectively; Fig. 1).

Figure 1

Propensity Score Analysis for Single Study Drug

There were significant differences in demographic and clinical characteristics between statin‐users versus statin nonusers, and between beta‐blocker users versus beta‐blocker nonusers. These differences became insignificant after the propensity score adjustment, with the exception of hyperlipidemia for statins, P = .02, which was added to the model as a confounder (Table 2). The distribution of the propensity scores was similar for study drug users and nonusers within each stratum. The association with decreased mortality remained significant after adjusting for propensity score (for statins, HR = 0.78 [95% CI 0.670.92, P = .0050], number needed to treat [NNT] = 22; for beta‐blockers HR = 0.84 [95% CI 0.730.96, P = .0103], NNT = 30; Fig. 2).

Figure 2

DISCUSSION

In this retrospective observational study we found that after vascular surgery the use of propensity‐adjusted statins compared with no use of statins reduced long‐term mortality over the study period by 22%, with a number needed to treat of 22, and the use of propensity‐adjusted beta‐blockers compared with no use also reduced long‐term mortality, by 16%, with a number needed to treat of 30. There were no statistically significant differences between outcomes of statin users and beta‐blocker users. In addition, using a propensity‐adjusted combination of statin and beta‐blockers compared with using neither decreased mortality overall by 44%, with a number needed to treat of 9. We focused on the use of outpatient drugs 30 days before or after surgery, as the timing of potentially beneficial medications has not been clearly established. Over time, more patients originally categorized as not taking a study drug began taking one, so that by 2 years after surgery, 58% of the patients were taking a statin, and 67% were taking a beta‐blocker, compared with 44% and 53%, respectively, of the study cohort initially. This would have made it more difficult to demonstrate a difference between these 2 groups. As more patients ended up taking the study drugs over time than the originally identified study drug users, and a mortality difference was still demonstrated, there may be an increased advantage in taking the study drugs around the time of surgery. As our focus was on long‐term postoperative mortality, which has not commonly been studied according to the literature, we preferred to also focus on long‐term, chronic ambulatory use of the study drugs. We did perform a subcohort analysis of the timing of study drug use. This confirmed that this cohort predominately comprised long‐term users of the study drugs who took the drug both before and after surgery. This study was not powered to comment on 30‐day mortality.

Perioperative beta‐blockers have been shown in retrospective cohort studies, case‐control studies, randomized clinical trials, meta‐analyses, and systematic reviews to decrease mortality and morbidity after noncardiac surgery. Although recent studies have not shown a benefit for more moderate‐ to low‐risk subjects,11, 12 perioperative beta‐blockers are still considered an indicator of health care quality in the United States.25 At present, perioperative beta‐blockers have an ACC/AHA class I indication (should be administered; Evidence level C) for patients undergoing vascular surgery with a positive stress test, and class IIa indication (reasonable to administer; Evidence level B) for vascular surgery patients with coronary heart disease or multiple clinical risk factors.26 A recent observational study in noncardiac surgery patients demonstrated perioperative beta‐blockers may be most helpful to prevent in‐hospital death after surgery of patients with an RCRI 2 and may be unhelpful or harmful for patients with an RCRI 1.27 Our univariate RCRI findings did not agree, as we found all patients whatever their level of risk benefited from perioperative use of beta‐blockers, alone or in combination. Our study population was older, had a higher RCRI, and underwent comparatively higher‐risk surgery, we were investigating longer‐term outcome, and we concentrated on ambulatory use of beta‐blockers, which may have contributed to the divergence in findings. Our propensity‐adjusted RCRI analysis did not show beta‐blockers associated with any change in mortality at any patient risk level. This may be, in part, because of the reduced number of patients in the RCRI strata. RCRI stratum‐specific analysis is limited by the number of patients and deaths in each RCRI stratum. For example, the power to detect a 2‐year difference of 10% (or 5%) between statin users and nonusers is approximately 99% (66%), 99% (59%), 92% (42%), and 61% (23%) for RCRI = 0, 1, 2, and 3, respectively.

Case‐control and retrospective cohort studies and one randomized clinical trial have shown perioperative statins to decrease either short‐term cardiovascular morbidity or mortality up to 30 days after surgery, and a limited number of retrospective cohort studies have shown reduced mortality for longer‐term follow‐up.1418, 28 There was one previous preliminary study of vascular surgery patients that demonstrated an additive benefit of using statins and beta‐blockers up to 30 days after surgery. This additive effect was only observed in patients with an RCRI 3.29 The results of our longer‐term follow‐up study of a larger cohort did not agree. Compared with patients who did not take a statin or a beta‐blocker, those patients who took both study drugs decreased their relative risk of mortality by approximately 36% in propensity‐ adjusted analysis and by about 50% in univariate analysis, regardless of patient‐specific risk level. For example, in the propensity‐adjusted analysis, the healthiest patients with an RCRI of 0 who took both study drugs had lower mortality than patients who took neither study drug, 8% versus 14%, a 38% relative reduction in mortality, with a number needed to treat of 20 (P = .0184).

In addition, the use of the RCRI for the first time highlighted the divergent long‐term mortality rates for patient‐specific risk levels and the striking long‐term associations of the perioperative use of ambulatory statins, beta‐blockers, and both drugs in combination with improved long‐term mortality. The long‐term use of the study drugs may indeed help all patients with atherosclerotic vascular disease, regardless of surgery. However, vascular surgery presents an opportunity for medical intervention, and our results are most applicable for these patients. In addition, the perioperative state has a unique physiology of acute and intense inflammation and thrombosis. Beta‐blockers and statins have antiadrenergic, anti‐inflammatory, and antithrombotic properties that may be beneficial during this high‐risk state.

Our findings should be viewed with some caution. The use of ICD‐9 codes and demographic data is dependent on the documentation and coding of comorbidities in the medical record and database. The use of statins and beta‐blockers was not random, and patients who took statins and beta‐blockers were different than those who did not. We used rigorous propensity and multivariate analysis, including controlling for clonidine, which has been shown to decrease death after vascular surgery.30 We also controlled for serum albumin level, which has been shown to be a leading predictor of postoperative death.31 We further separately stratified patients by RCRI, as this was a powerful predictor of death in the univariate analysis, but because of the retrospective nature of the study, unmeasured confounders may exist. Only 1% of the study patients were women, which is a limitation of the study. This administrative database is also limited by not having information on tobacco use for 47% of the patients and by not knowing ethnicity for 80% of the patients.

The use of perioperative statins and beta‐blockers used alone or in combination was associated with a reduction in long‐term mortality for vascular surgery patients, and combination use benefited patients at all levels of risk. Higher‐risk patients benefited most by taking both study drugs. These findings extend prior data, add to the natural history of long‐term postoperative outcomes, and also support clinical trials that would evaluate the prospective use of both these medications in vascular surgery patients with attention to patient‐specific risk level. Until the results of 2 randomized controlled trials become available, which may further clarify the use of perioperative statins and beta‐blockers in noncardiac, and noncardiac vascular surgery,13, 32 the use of statins and beta‐blockers should be considered for all patients undergoing vascular surgery. In addition, long‐term use of statins and beta‐blockers for all patients with atherosclerotic vascular disease should be considered.33

Vascular surgery has higher morbidity and mortality than other noncardiac surgeries. Despite the identification of vascular surgery as higher risk, 30‐day mortality for this surgery has remained at 3%10%. Few studies have examined longer‐term outcomes, but higher mortality rates have been reported, for example, 10%30% 6 months after surgery, 20%40% 1 year after surgery, and 30%50% 5 years after surgery.15 Postoperative adverse events have been found to be highly correlated with perioperative ischemia and infarction.68 Perioperative beta‐blockers have been widely studied and have been shown to benefit patients undergoing noncardiac surgery generally and vascular surgery specifically.9, 10 However, 2 recent trials of perioperative beta‐blockers in noncardiac and vascular surgery patients failed to show an association with 18‐month and 30‐day postoperative morbidity and mortality, respectively.11, 12 In addition, the authors of a recent meta‐analysis of perioperative beta‐blockers suggested more studies were needed.13 Furthermore, there have been promising new data on the use of perioperative statins.1418 Finally, as a recent clinical trial of revascularization before vascular surgery did not demonstrate an advantage over medical management, the identification of which perioperative medicines improve postoperative outcomes and in what combinations becomes even more important.19 We sought to ascertain if the ambulatory use of statins and/or beta‐blockers within 30 days of surgery was associated with a reduction in long‐term mortality.

METHODS

RESULTS