Case Report

A 52‐year‐old woman with chronic hepatitis C was admitted with complaints of dry cough, shortness of breath, and fever. Four days prior to admission, she had successfully finished a 44‐week course of pegylated interferon (IFN) alpha and ribavirin with undetectable viral load on completion of treatment. At 30 weeks, she had developed a dry cough, which she initially ignored. Three weeks later, as a result of a violent coughing episode, she sustained a spontaneous uncomplicated fracture of the left sixth rib. Chest x‐ray at that time did not show an infiltrate or opacity. She continued treatment, and over the next 6 weeks developed progressive dyspnea on exertion. Five days prior to admission, she had developed fever of 101F. Repeat chest x‐ray revealed a left lingular infiltrate and she was prescribed levofloxacin. Her symptoms failed to improve and she was admitted to the hospital.

On admission, she denied expectoration, sore throat, night sweats, or rashes. She also denied tobacco use, pets at home, or recent travel outside the Midwest. Examination revealed a temperature of 99.4F and decreased breath sounds over the left lower chest. Chest x‐ray revealed left‐sided pleural effusion. D‐dimer was negative. Computed tomography (CT) scan of the chest showed a left lingular infiltrate, right lower lobe ground‐glass opacity, and a moderately‐sized left pleural effusion. Azithromycin, piperacillin/tazobactam, and vancomycin were empirically started. Over the next 36 hours, she became increasingly tachypneic and short of breath. A diagnostic and therapeutic thoracentesis with aspiration of 800 mL of light‐yellow‐colored fluid brought symptomatic relief. Pleural fluid analysis revealed an exudative effusion with 3.8 gm/dL of protein (serum protein = 6.2 gm/dL), lactic dehydrogenase (LDH) of 998 IU/L (serum LDH = 293 IU/L), and normal adenosine deaminase. The cell count was 362 per mm³ with 37% lymphocytes, 32% macrophages, 26% neutrophils, and 1% eosinophils. There were no atypical or malignant cells. Bacterial, fungal, viral, acid‐fast stains and cultures, and polymerase chain reaction (PCR) for Mycobacterium tuberculosis were all negative. An echocardiogram and plasma B‐type natriuretic peptide were normal.

Serum antinuclear and antineutrophilic cytoplasmic antibodies, Bordetella pertussis PCR, serologies for Mycoplasma, Chlamydia, Coxiella, and urinary antigens for Legionella and Blastomyces were all negative. Bronchoscopy with bronchoalveolar lavage (BAL) was performed on hospital day 5. BAL stains and cultures for bacteria, fungi, acid‐fast organisms, Cytomegalovirus, Herpes simplex virus, Legionella, and Pneumocystis were negative. Cytology revealed mild acute inflammation with macrophage predominance and no malignant cells.

Repeat CT scan of the chest on day 6 showed bilateral ground‐glass infiltrates and persistent left pleural effusion (Figure 1). In the absence of an identifiable cause, the patient was diagnosed with interstitial pneumonitis and pleural effusion secondary to pegylated IFN alpha and ribavirin. Treatment with steroids was considered, but was not used due to recent successful suppression of hepatitis C. She was discharged with continued close follow‐up. Her fever gradually subsided over the next 2 weeks and her cough continued to improve over the next 6 weeks. Follow‐up CT scan of the chest 3 months after discharge showed complete resolution of the left pleural effusion and near‐resolution of the bilateral basal infiltrates.

Figure 1

Discussion

Use of IFN alpha has been associated with multiple forms of lung toxicity, of which interstitial pneumonitis and granulomatous inflammation resembling sarcoidosis are the most common. Unusual forms include isolated nonproductive cough, exacerbation of asthma, organizing pneumonia, pleural effusion, adult respiratory distress syndrome, and exacerbation of vasculitis.1 Reports of adverse pulmonary effects of ribavirin are sparse, and it has not been implicated as a sole etiologic agent in causing lung toxicity. It is therefore likely that pulmonary toxicity observed in patients with hepatitis C virus (HCV) infection undergoing IFN alpha and ribavirin therapy is due to the IFN.

Pleural effusion may accompany the IFN‐induced capillary leak syndrome.2

There have been only 2 other cases of pleural effusion during treatment with IFN alpha described to date.3, 4 Takeda et al.3 described a 54‐year‐old male who was accidentally detected to have a moderate‐sized right pleural effusion on magnetic resonance imaging (MRI) of the abdomen, 14 days after therapy with recombinant IFN alpha was initiated. The pleural fluid was a lymphocyte‐predominant exudate and resolved approximately 4 months after discontinuation of IFN treatment. Tsushima et al.4 reported bilateral pleural effusions and ground‐glass opacities in a patient treated with IFN for metastatic renal cell cancer that resolved following a course of steroids.

IFN‐related pulmonary toxicity has been reported to typically develop between 2 and 16 weeks of treatment. Our patient had a delayed onset of symptoms at 30 weeks and progressed on to develop left pleural effusion and pulmonary infiltrates by the time she finished 44 weeks of treatment. We ruled out infectious, malignant, cardiac, and autoimmune causes, which often present in a similar fashion.

BAL fluid cytology in our patient revealed predominant macrophages. Yamaguchi et al., in their analysis of BAL fluid in patients with hepatitis C, demonstrated increased macrophages (76% and 77.5%) and lymphocytes (19.8% and 18.8%) before and after treatment with IFN alpha, respectively.

The cornerstone of management of lung toxicity due to IFN is to diminish or stop use of the offending agent. Our patient demonstrated complete recovery of symptoms and radiological resolution within 3 months of completion of IFN therapy, without corticosteroid therapy. Although corticosteroid regimes of 6 to 12 months have been used to manage IFN related lung toxicity, most patients recover without them.6 Moreover, corticosteroids have been implicated in the recurrence of hepatitis C.

We believe that our patient's pathology is most consistent with lung and pleural toxicity temporally related to IFN treatment. Through our case report, we bring to attention this infrequent complication, and emphasize its self‐limited course upon withdrawal of the offending agent.

Case Report

A 52‐year‐old woman with chronic hepatitis C was admitted with complaints of dry cough, shortness of breath, and fever. Four days prior to admission, she had successfully finished a 44‐week course of pegylated interferon (IFN) alpha and ribavirin with undetectable viral load on completion of treatment. At 30 weeks, she had developed a dry cough, which she initially ignored. Three weeks later, as a result of a violent coughing episode, she sustained a spontaneous uncomplicated fracture of the left sixth rib. Chest x‐ray at that time did not show an infiltrate or opacity. She continued treatment, and over the next 6 weeks developed progressive dyspnea on exertion. Five days prior to admission, she had developed fever of 101F. Repeat chest x‐ray revealed a left lingular infiltrate and she was prescribed levofloxacin. Her symptoms failed to improve and she was admitted to the hospital.

On admission, she denied expectoration, sore throat, night sweats, or rashes. She also denied tobacco use, pets at home, or recent travel outside the Midwest. Examination revealed a temperature of 99.4F and decreased breath sounds over the left lower chest. Chest x‐ray revealed left‐sided pleural effusion. D‐dimer was negative. Computed tomography (CT) scan of the chest showed a left lingular infiltrate, right lower lobe ground‐glass opacity, and a moderately‐sized left pleural effusion. Azithromycin, piperacillin/tazobactam, and vancomycin were empirically started. Over the next 36 hours, she became increasingly tachypneic and short of breath. A diagnostic and therapeutic thoracentesis with aspiration of 800 mL of light‐yellow‐colored fluid brought symptomatic relief. Pleural fluid analysis revealed an exudative effusion with 3.8 gm/dL of protein (serum protein = 6.2 gm/dL), lactic dehydrogenase (LDH) of 998 IU/L (serum LDH = 293 IU/L), and normal adenosine deaminase. The cell count was 362 per mm³ with 37% lymphocytes, 32% macrophages, 26% neutrophils, and 1% eosinophils. There were no atypical or malignant cells. Bacterial, fungal, viral, acid‐fast stains and cultures, and polymerase chain reaction (PCR) for Mycobacterium tuberculosis were all negative. An echocardiogram and plasma B‐type natriuretic peptide were normal.

Serum antinuclear and antineutrophilic cytoplasmic antibodies, Bordetella pertussis PCR, serologies for Mycoplasma, Chlamydia, Coxiella, and urinary antigens for Legionella and Blastomyces were all negative. Bronchoscopy with bronchoalveolar lavage (BAL) was performed on hospital day 5. BAL stains and cultures for bacteria, fungi, acid‐fast organisms, Cytomegalovirus, Herpes simplex virus, Legionella, and Pneumocystis were negative. Cytology revealed mild acute inflammation with macrophage predominance and no malignant cells.

Repeat CT scan of the chest on day 6 showed bilateral ground‐glass infiltrates and persistent left pleural effusion (Figure 1). In the absence of an identifiable cause, the patient was diagnosed with interstitial pneumonitis and pleural effusion secondary to pegylated IFN alpha and ribavirin. Treatment with steroids was considered, but was not used due to recent successful suppression of hepatitis C. She was discharged with continued close follow‐up. Her fever gradually subsided over the next 2 weeks and her cough continued to improve over the next 6 weeks. Follow‐up CT scan of the chest 3 months after discharge showed complete resolution of the left pleural effusion and near‐resolution of the bilateral basal infiltrates.

Figure 1

Discussion

Use of IFN alpha has been associated with multiple forms of lung toxicity, of which interstitial pneumonitis and granulomatous inflammation resembling sarcoidosis are the most common. Unusual forms include isolated nonproductive cough, exacerbation of asthma, organizing pneumonia, pleural effusion, adult respiratory distress syndrome, and exacerbation of vasculitis.1 Reports of adverse pulmonary effects of ribavirin are sparse, and it has not been implicated as a sole etiologic agent in causing lung toxicity. It is therefore likely that pulmonary toxicity observed in patients with hepatitis C virus (HCV) infection undergoing IFN alpha and ribavirin therapy is due to the IFN.

Pleural effusion may accompany the IFN‐induced capillary leak syndrome.2

There have been only 2 other cases of pleural effusion during treatment with IFN alpha described to date.3, 4 Takeda et al.3 described a 54‐year‐old male who was accidentally detected to have a moderate‐sized right pleural effusion on magnetic resonance imaging (MRI) of the abdomen, 14 days after therapy with recombinant IFN alpha was initiated. The pleural fluid was a lymphocyte‐predominant exudate and resolved approximately 4 months after discontinuation of IFN treatment. Tsushima et al.4 reported bilateral pleural effusions and ground‐glass opacities in a patient treated with IFN for metastatic renal cell cancer that resolved following a course of steroids.

IFN‐related pulmonary toxicity has been reported to typically develop between 2 and 16 weeks of treatment. Our patient had a delayed onset of symptoms at 30 weeks and progressed on to develop left pleural effusion and pulmonary infiltrates by the time she finished 44 weeks of treatment. We ruled out infectious, malignant, cardiac, and autoimmune causes, which often present in a similar fashion.

BAL fluid cytology in our patient revealed predominant macrophages. Yamaguchi et al., in their analysis of BAL fluid in patients with hepatitis C, demonstrated increased macrophages (76% and 77.5%) and lymphocytes (19.8% and 18.8%) before and after treatment with IFN alpha, respectively.

The cornerstone of management of lung toxicity due to IFN is to diminish or stop use of the offending agent. Our patient demonstrated complete recovery of symptoms and radiological resolution within 3 months of completion of IFN therapy, without corticosteroid therapy. Although corticosteroid regimes of 6 to 12 months have been used to manage IFN related lung toxicity, most patients recover without them.6 Moreover, corticosteroids have been implicated in the recurrence of hepatitis C.

We believe that our patient's pathology is most consistent with lung and pleural toxicity temporally related to IFN treatment. Through our case report, we bring to attention this infrequent complication, and emphasize its self‐limited course upon withdrawal of the offending agent.

Case Report

A 52‐year‐old woman with chronic hepatitis C was admitted with complaints of dry cough, shortness of breath, and fever. Four days prior to admission, she had successfully finished a 44‐week course of pegylated interferon (IFN) alpha and ribavirin with undetectable viral load on completion of treatment. At 30 weeks, she had developed a dry cough, which she initially ignored. Three weeks later, as a result of a violent coughing episode, she sustained a spontaneous uncomplicated fracture of the left sixth rib. Chest x‐ray at that time did not show an infiltrate or opacity. She continued treatment, and over the next 6 weeks developed progressive dyspnea on exertion. Five days prior to admission, she had developed fever of 101F. Repeat chest x‐ray revealed a left lingular infiltrate and she was prescribed levofloxacin. Her symptoms failed to improve and she was admitted to the hospital.

On admission, she denied expectoration, sore throat, night sweats, or rashes. She also denied tobacco use, pets at home, or recent travel outside the Midwest. Examination revealed a temperature of 99.4F and decreased breath sounds over the left lower chest. Chest x‐ray revealed left‐sided pleural effusion. D‐dimer was negative. Computed tomography (CT) scan of the chest showed a left lingular infiltrate, right lower lobe ground‐glass opacity, and a moderately‐sized left pleural effusion. Azithromycin, piperacillin/tazobactam, and vancomycin were empirically started. Over the next 36 hours, she became increasingly tachypneic and short of breath. A diagnostic and therapeutic thoracentesis with aspiration of 800 mL of light‐yellow‐colored fluid brought symptomatic relief. Pleural fluid analysis revealed an exudative effusion with 3.8 gm/dL of protein (serum protein = 6.2 gm/dL), lactic dehydrogenase (LDH) of 998 IU/L (serum LDH = 293 IU/L), and normal adenosine deaminase. The cell count was 362 per mm³ with 37% lymphocytes, 32% macrophages, 26% neutrophils, and 1% eosinophils. There were no atypical or malignant cells. Bacterial, fungal, viral, acid‐fast stains and cultures, and polymerase chain reaction (PCR) for Mycobacterium tuberculosis were all negative. An echocardiogram and plasma B‐type natriuretic peptide were normal.

Serum antinuclear and antineutrophilic cytoplasmic antibodies, Bordetella pertussis PCR, serologies for Mycoplasma, Chlamydia, Coxiella, and urinary antigens for Legionella and Blastomyces were all negative. Bronchoscopy with bronchoalveolar lavage (BAL) was performed on hospital day 5. BAL stains and cultures for bacteria, fungi, acid‐fast organisms, Cytomegalovirus, Herpes simplex virus, Legionella, and Pneumocystis were negative. Cytology revealed mild acute inflammation with macrophage predominance and no malignant cells.

Repeat CT scan of the chest on day 6 showed bilateral ground‐glass infiltrates and persistent left pleural effusion (Figure 1). In the absence of an identifiable cause, the patient was diagnosed with interstitial pneumonitis and pleural effusion secondary to pegylated IFN alpha and ribavirin. Treatment with steroids was considered, but was not used due to recent successful suppression of hepatitis C. She was discharged with continued close follow‐up. Her fever gradually subsided over the next 2 weeks and her cough continued to improve over the next 6 weeks. Follow‐up CT scan of the chest 3 months after discharge showed complete resolution of the left pleural effusion and near‐resolution of the bilateral basal infiltrates.

Figure 1

Discussion

Use of IFN alpha has been associated with multiple forms of lung toxicity, of which interstitial pneumonitis and granulomatous inflammation resembling sarcoidosis are the most common. Unusual forms include isolated nonproductive cough, exacerbation of asthma, organizing pneumonia, pleural effusion, adult respiratory distress syndrome, and exacerbation of vasculitis.1 Reports of adverse pulmonary effects of ribavirin are sparse, and it has not been implicated as a sole etiologic agent in causing lung toxicity. It is therefore likely that pulmonary toxicity observed in patients with hepatitis C virus (HCV) infection undergoing IFN alpha and ribavirin therapy is due to the IFN.

Pleural effusion may accompany the IFN‐induced capillary leak syndrome.2

There have been only 2 other cases of pleural effusion during treatment with IFN alpha described to date.3, 4 Takeda et al.3 described a 54‐year‐old male who was accidentally detected to have a moderate‐sized right pleural effusion on magnetic resonance imaging (MRI) of the abdomen, 14 days after therapy with recombinant IFN alpha was initiated. The pleural fluid was a lymphocyte‐predominant exudate and resolved approximately 4 months after discontinuation of IFN treatment. Tsushima et al.4 reported bilateral pleural effusions and ground‐glass opacities in a patient treated with IFN for metastatic renal cell cancer that resolved following a course of steroids.

IFN‐related pulmonary toxicity has been reported to typically develop between 2 and 16 weeks of treatment. Our patient had a delayed onset of symptoms at 30 weeks and progressed on to develop left pleural effusion and pulmonary infiltrates by the time she finished 44 weeks of treatment. We ruled out infectious, malignant, cardiac, and autoimmune causes, which often present in a similar fashion.

BAL fluid cytology in our patient revealed predominant macrophages. Yamaguchi et al., in their analysis of BAL fluid in patients with hepatitis C, demonstrated increased macrophages (76% and 77.5%) and lymphocytes (19.8% and 18.8%) before and after treatment with IFN alpha, respectively.

The cornerstone of management of lung toxicity due to IFN is to diminish or stop use of the offending agent. Our patient demonstrated complete recovery of symptoms and radiological resolution within 3 months of completion of IFN therapy, without corticosteroid therapy. Although corticosteroid regimes of 6 to 12 months have been used to manage IFN related lung toxicity, most patients recover without them.6 Moreover, corticosteroids have been implicated in the recurrence of hepatitis C.

We believe that our patient's pathology is most consistent with lung and pleural toxicity temporally related to IFN treatment. Through our case report, we bring to attention this infrequent complication, and emphasize its self‐limited course upon withdrawal of the offending agent.

Atrial fibrillation (AF), the most common clinically significant cardiac arrhythmia, affects over 2.3 million people in the United States.1 AF is associated with an increased risk of stroke and heart failure and independently increases the risk of all cause mortality.26 As such, AF confers a staggering healthcare cost burden.7, 8 Pharmacologic treatments to restore sinus rhythm in patients with AF are associated with a considerable relapse rate911 and the development of nonpharmacologic treatments for AF, such as catheter ablation procedures,1214 may be significantly more successful in restoring and maintaining sinus rhythm.15, 16 Despite relatively poor results from early catheter ablation techniques, the practice has evolved and boasts short‐term success rates as high as 73% to 91% depending on the specific type of procedure.17

In light of the success of ablative therapy, this approach, which was once used primarily in younger patients with structurally intact hearts, has been expanded to include more medically complex patients, including elderly patients, those with cardiomyopathy, and those with implanted devices.16, 18 At the same time, catheter ablation is not without complications, with major complications observed in up to 6% of cases,19 and significant costs.20 Moreover, while the most optimistic randomized control data demonstrate the ability of catheter ablation to prevent the recurrence of AF at 1 year,12, 21, 22 long‐term outcome data are lacking, particularly in patients older than 65 years or those with heart failure.17, 23

The encouraging results supporting catheter ablation continue to stimulate the utilization of catheter ablation practices and spur innovations in ablation techniques.24 The American College of Cardiology/American Heart Association/European Society of Cardiology consensus guidelines recommend consideration of ablative therapy in many instances of AF.17 AF is primarily a disease of older adults25 and although most studies have focused on younger individuals,26 it is possible that increasing numbers of older patients are receiving ablation therapy.16 Although single center studies are available,16 there are few data about the characteristics of patients undergoing ablative therapy on a national level. In order to better understand the current use of catheter ablation treatment for AF, we analyzed data from the National Hospital Discharge Survey (NHDS) to explore trends in patient characteristics and rates of ablation procedures in hospitalized patients with AF from the years 1990 to 2005.

Methods

The NHDS is a nationally representative study of hospitalized patients conducted annually by the National Center for Health Statistics,27 which collects data from approximately 270,000 inpatient records using a representative sample of about 500 short‐stay nonfederal hospitals in the United States. Data for each patient are obtained for age, sex, hospital geographic region (Northeast, Midwest, South, West), and hospital bed size, as well as up to 7 diagnostic codes and 4 procedural codes using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD‐9‐CM). Of note, data on race/ethnicity were not consistently coded in the NHDS and are therefore not included in this analysis.

We searched for all patients age 18 years or older who had an ICD‐9‐CM diagnosis of AF (427.31). Of these patients, we then identified those who had a procedure code for nonsurgical ablation of lesions or tissues of the heart via peripherally‐inserted catheter or an endovascular approach (37.34). We also searched for specific ICD‐9‐CM‐coded diagnoses corresponding to higher stroke risk according to the (CHADS₂) risk index,28 where 1 point is assigned for congestive heart failure, hypertension, age >75 years, or diabetes mellitus, and 2 points for prior stroke or transient ischemic attack. We calculated a CHADS₂ score for each patient.

Results

From 1990 to 2005, we identified 269,471 hospitalizations in the NHDS with a diagnosis of AF, of which 1,144 (0.42%) had a procedure code for catheter ablation. When extrapolated to national estimates, this corresponds to 32 million hospitalizations of patients with AF in the United States during the time period, of which 133,003 underwent ablation. The proportion of patients with AF who had ablation increased significantly over time, from 0.06% in 1990 to 0.79% in 2005 (P < 0.001 for trend; Figure 1).

Figure 1

On univariate analysis, people with AF undergoing ablation were on average younger and more likely to be male than those who did not have ablation (Table 1). The rate of catheter ablation was higher in patients younger than 50 years (1.75%) compared to 0.55% in patients aged 50 to 79 years, and 0.16% in patients aged 80 years or older. However, ablation rates increased significantly in all age groups over time, with no one age group increasing at a significantly faster rate than the others (P value for interaction between age categories and hospitalization year = 0.7; Figure 2). People undergoing ablation tended to have lower CHADS₂ stroke risk scores and fewer risk factors for stroke, including heart failure, coronary artery disease, and diabetes mellitus (Table 1).

Figure 2

People who underwent ablation were more likely to have private insurance as their primary source of payment and less likely to have Medicare (Table 1). Ablation rates were higher among patients with AF hospitalized in the Western and Southern regions of the United States (0.52% and 0.53%, respectively), compared to rates in the Midwest (0.30%) and Northeast (0.40%). Hospital bed‐size was significantly related to the frequency of ablation, with the overall rate of ablation in patients with AF being 0.04% in hospitals with 6 to 99 beds compared to 1.37% in hospitals with at least 500 beds (P < 0.001). Length of stay was shorter in patients with ablations compared to patients without ablation therapy, and patients with ablation were more likely to be discharged home (Table 1). The inpatient mortality rate in patients undergoing ablation was quite low (0.96%).

In multivariate analysis, the likelihood of ablation therapy in a hospitalized patient with AF increased by 15% per year (95% confidence interval [CI], 13%‐16%) over the time period, adjusted for clinical and hospital characteristics. The likelihood of ablation decreased with older age (adjusted odds ratio [aOR], 0.7 [95% CI, 0.6‐0.7] for each decade of age over 50 years) and for each 1‐point increase in CHADS₂ score (aOR, 0.7 [95% CI, 0.7‐0.8]). Ablation was significantly more likely to be performed in hospitals with larger bed‐sizes (aOR, 27.4 [95% CI, 16.1‐46.6] comparing bed‐size of 500+ to bed‐size of 6 to 99) and in patients with private insurance (aOR, 1.4 [95% CI, 1.2‐1.6]; Table 2). The goodness‐of‐fit of the model was appropriate, with a nonsignificant Hosmer‐Lemeshow test P value of 0.13.

To account for the possibility that the ablation procedure was not specifically for AF, we performed a subgroup analysis that excluded all patients who also had diagnostic codes for supraventricular or ventricular tachycardias (427.0, 427.1, 427.2, and 427.4), or atrial flutter (427.32). Of the 269,471 hospitalizations with AF, 23,069 (8.6%) had a code for an arrhythmia in addition to AF. When we excluded patients with other arrhythmias, we identified 691 patients who underwent ablation and who only had a diagnosis of AF. An analysis of this subset yielded results similar to the full analysis (Table 2). The likelihood of ablation therapy in this subset of patients with only AF increased by 14% per year (95% CI, 11%‐16%), adjusting for patient age, sex, insurance status, CHADS₂ score, hospital region, and hospital bed‐size.

Discussion

The proportion of hospitalized patients with AF who undergo ablation therapy in the United States has been increasing by approximately 15% per year over the last 15 years. Patients receiving ablation therapy are more likely to be younger, have private insurance, and have fewer stroke risk factors. These demographics likely reflect the fact that these ablations are elective procedures that are preferentially performed in healthier, lower‐risk patients. Despite these preferences, the rate of ablation therapy has been increasing significantly across all age groups, even in the oldest patients.

Though limited by relatively short follow‐up data, published studies of ablation therapies for AF show promising results,17, 26 and initial cost analyses suggest possible fiscal benefits of ablation for AF.20 Despite a paucity of randomized clinical trials comparing ablation to pharmacologic rhythm and rate control, studies suggest that quality of life may be significantly improved with ablation as compared to antiarrhythmic drugs.21 This may be because ablation may reduce AF‐related symptoms.12 As ablation becomes more widespread and recommended, physicians, including hospitalists, may be increasingly likely to refer their patients for ablation, even for patient subgroups who were not well‐represented in clinical trial settings.

The inpatient mortality rate in patients undergoing ablation therapy was quite low in our study, although ablation is not without some risk of procedure‐related stroke and other complications.19 An analysis of the compiled studies on ablation for AF estimates that major complication such as cardiac tamponade or thromboembolism occur in as many as 7% of patients.26 Patients are at highest risk for embolic events, such as transient ischemic attacks or ischemic strokes, in the immediate hours to weeks after ablation. An estimated 5% to 25% of patients will develop a new arrhythmia at some point in the postablation period and other complications, including esophageal injury, phrenic nerve injury, groin hematoma, and retroperitoneal bleed, have been observed.26 Increasing comanagement of postablation patients will necessitate that hospitalists understand the potential complications of ablation as well as current strategies for bridging anticoagulation therapy.

Few data are available about the safety and efficacy of catheter ablation for patients over the age of 65 years. In fact, the mean age of patients enrolled in most clinical trials of catheter ablation was younger than 60 years.26, 29 There are also limited data about the long‐term efficacy of ablation therapy in patients with structural heart disease30; despite this, our study shows that a quarter of patients with AF undergoing ablation therapy in the United States have diagnosed heart failure. As always, the optimistic introduction of new technologies to unstudied patient populations carries the risk of unintended harm. Hospitalists are well situated to collect and analyze outcome data for older patients with multiple comorbidities and to provide real‐time monitoring of potential complications.

Few studies have focused on the demographic and comorbid characteristics of patients undergoing ablation for AF on a national level. One study examined characteristics of patients referred to a single academic center for AF ablation from 1999 to 2005 and found that referred patients have, over time, been older (mean age 47 years in 1999 versus 56 years in 2005), have more persistent AF, larger atria, and were more likely to have had a history of cardiomyopathy (0% in 1999 versus 16% in 2006).16 This study also reported that men were consistently more likely to be referred for ablation than women. These results are generally consistent with our findings.

Our study has several limitations. The exact indication and specific type of ablation were not available in the NHDS, and it is possible that the ablation procedure was for an arrhythmia other than AF. However, our analysis of the subset of patients who only had AF as a diagnosis yielded results similar to the full analysis. We were unable to assess specific efficacy or complication data, but mortality was low and patients tended to have short hospital stays. Because the NHDS samples random hospitalizations, it is possible that some patients were overrepresented in the database if they were repeatedly hospitalized in a single year. This could potentially bias our results toward an overestimate of the number of patients who receive ablation.

It remains unclear what proportion of AF ablation procedures occur in the outpatient versus inpatient setting. Inpatient versus outpatient status is not specified in the few single‐center ablation experiences reported in the literature,16 and the few trials reported are not reliable for determining practice in a nonstudy setting. The most recent (2006) Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society Expert Consensus Statement on Catheter and Surgical Ablation of AF recommends aggressive anticoagulation in the periprocedure period with either heparin or low‐molecular‐weight heparins, followed by a bridge to warfarin.17 It makes intuitive sense that patients undergoing ablation for AF would be admitted at least overnight to bridge anticoagulation therapy and monitor for complications, but widespread use of low‐molecular‐weight heparin may make hospitalization less necessary. The observation that patients undergoing ablation had shorter hospital stays does not necessarily imply that ablation procedures shorten hospital stays. Rather, the data almost certainly reflect the fact that ablations are mostly elective procedures performed in the setting of planned short‐term admissions.

Our study provides important epidemiologic data about national trends in the use of ablation therapy in hospitalized patients with AF. We find that the rate of catheter ablation in patients with AF has been increasing significantly over time and across all age groups, including the oldest patients. As the proportion of patients with AF who receive ablation therapy continues to increase over time, comprehensive long‐term outcome data and cost‐effectiveness analyses will be important.

Atrial fibrillation (AF), the most common clinically significant cardiac arrhythmia, affects over 2.3 million people in the United States.1 AF is associated with an increased risk of stroke and heart failure and independently increases the risk of all cause mortality.26 As such, AF confers a staggering healthcare cost burden.7, 8 Pharmacologic treatments to restore sinus rhythm in patients with AF are associated with a considerable relapse rate911 and the development of nonpharmacologic treatments for AF, such as catheter ablation procedures,1214 may be significantly more successful in restoring and maintaining sinus rhythm.15, 16 Despite relatively poor results from early catheter ablation techniques, the practice has evolved and boasts short‐term success rates as high as 73% to 91% depending on the specific type of procedure.17

In light of the success of ablative therapy, this approach, which was once used primarily in younger patients with structurally intact hearts, has been expanded to include more medically complex patients, including elderly patients, those with cardiomyopathy, and those with implanted devices.16, 18 At the same time, catheter ablation is not without complications, with major complications observed in up to 6% of cases,19 and significant costs.20 Moreover, while the most optimistic randomized control data demonstrate the ability of catheter ablation to prevent the recurrence of AF at 1 year,12, 21, 22 long‐term outcome data are lacking, particularly in patients older than 65 years or those with heart failure.17, 23

The encouraging results supporting catheter ablation continue to stimulate the utilization of catheter ablation practices and spur innovations in ablation techniques.24 The American College of Cardiology/American Heart Association/European Society of Cardiology consensus guidelines recommend consideration of ablative therapy in many instances of AF.17 AF is primarily a disease of older adults25 and although most studies have focused on younger individuals,26 it is possible that increasing numbers of older patients are receiving ablation therapy.16 Although single center studies are available,16 there are few data about the characteristics of patients undergoing ablative therapy on a national level. In order to better understand the current use of catheter ablation treatment for AF, we analyzed data from the National Hospital Discharge Survey (NHDS) to explore trends in patient characteristics and rates of ablation procedures in hospitalized patients with AF from the years 1990 to 2005.

Methods

The NHDS is a nationally representative study of hospitalized patients conducted annually by the National Center for Health Statistics,27 which collects data from approximately 270,000 inpatient records using a representative sample of about 500 short‐stay nonfederal hospitals in the United States. Data for each patient are obtained for age, sex, hospital geographic region (Northeast, Midwest, South, West), and hospital bed size, as well as up to 7 diagnostic codes and 4 procedural codes using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD‐9‐CM). Of note, data on race/ethnicity were not consistently coded in the NHDS and are therefore not included in this analysis.

We searched for all patients age 18 years or older who had an ICD‐9‐CM diagnosis of AF (427.31). Of these patients, we then identified those who had a procedure code for nonsurgical ablation of lesions or tissues of the heart via peripherally‐inserted catheter or an endovascular approach (37.34). We also searched for specific ICD‐9‐CM‐coded diagnoses corresponding to higher stroke risk according to the (CHADS₂) risk index,28 where 1 point is assigned for congestive heart failure, hypertension, age >75 years, or diabetes mellitus, and 2 points for prior stroke or transient ischemic attack. We calculated a CHADS₂ score for each patient.

Results

From 1990 to 2005, we identified 269,471 hospitalizations in the NHDS with a diagnosis of AF, of which 1,144 (0.42%) had a procedure code for catheter ablation. When extrapolated to national estimates, this corresponds to 32 million hospitalizations of patients with AF in the United States during the time period, of which 133,003 underwent ablation. The proportion of patients with AF who had ablation increased significantly over time, from 0.06% in 1990 to 0.79% in 2005 (P < 0.001 for trend; Figure 1).

Figure 1

On univariate analysis, people with AF undergoing ablation were on average younger and more likely to be male than those who did not have ablation (Table 1). The rate of catheter ablation was higher in patients younger than 50 years (1.75%) compared to 0.55% in patients aged 50 to 79 years, and 0.16% in patients aged 80 years or older. However, ablation rates increased significantly in all age groups over time, with no one age group increasing at a significantly faster rate than the others (P value for interaction between age categories and hospitalization year = 0.7; Figure 2). People undergoing ablation tended to have lower CHADS₂ stroke risk scores and fewer risk factors for stroke, including heart failure, coronary artery disease, and diabetes mellitus (Table 1).

Figure 2

People who underwent ablation were more likely to have private insurance as their primary source of payment and less likely to have Medicare (Table 1). Ablation rates were higher among patients with AF hospitalized in the Western and Southern regions of the United States (0.52% and 0.53%, respectively), compared to rates in the Midwest (0.30%) and Northeast (0.40%). Hospital bed‐size was significantly related to the frequency of ablation, with the overall rate of ablation in patients with AF being 0.04% in hospitals with 6 to 99 beds compared to 1.37% in hospitals with at least 500 beds (P < 0.001). Length of stay was shorter in patients with ablations compared to patients without ablation therapy, and patients with ablation were more likely to be discharged home (Table 1). The inpatient mortality rate in patients undergoing ablation was quite low (0.96%).

In multivariate analysis, the likelihood of ablation therapy in a hospitalized patient with AF increased by 15% per year (95% confidence interval [CI], 13%‐16%) over the time period, adjusted for clinical and hospital characteristics. The likelihood of ablation decreased with older age (adjusted odds ratio [aOR], 0.7 [95% CI, 0.6‐0.7] for each decade of age over 50 years) and for each 1‐point increase in CHADS₂ score (aOR, 0.7 [95% CI, 0.7‐0.8]). Ablation was significantly more likely to be performed in hospitals with larger bed‐sizes (aOR, 27.4 [95% CI, 16.1‐46.6] comparing bed‐size of 500+ to bed‐size of 6 to 99) and in patients with private insurance (aOR, 1.4 [95% CI, 1.2‐1.6]; Table 2). The goodness‐of‐fit of the model was appropriate, with a nonsignificant Hosmer‐Lemeshow test P value of 0.13.

To account for the possibility that the ablation procedure was not specifically for AF, we performed a subgroup analysis that excluded all patients who also had diagnostic codes for supraventricular or ventricular tachycardias (427.0, 427.1, 427.2, and 427.4), or atrial flutter (427.32). Of the 269,471 hospitalizations with AF, 23,069 (8.6%) had a code for an arrhythmia in addition to AF. When we excluded patients with other arrhythmias, we identified 691 patients who underwent ablation and who only had a diagnosis of AF. An analysis of this subset yielded results similar to the full analysis (Table 2). The likelihood of ablation therapy in this subset of patients with only AF increased by 14% per year (95% CI, 11%‐16%), adjusting for patient age, sex, insurance status, CHADS₂ score, hospital region, and hospital bed‐size.

Discussion

The proportion of hospitalized patients with AF who undergo ablation therapy in the United States has been increasing by approximately 15% per year over the last 15 years. Patients receiving ablation therapy are more likely to be younger, have private insurance, and have fewer stroke risk factors. These demographics likely reflect the fact that these ablations are elective procedures that are preferentially performed in healthier, lower‐risk patients. Despite these preferences, the rate of ablation therapy has been increasing significantly across all age groups, even in the oldest patients.

Though limited by relatively short follow‐up data, published studies of ablation therapies for AF show promising results,17, 26 and initial cost analyses suggest possible fiscal benefits of ablation for AF.20 Despite a paucity of randomized clinical trials comparing ablation to pharmacologic rhythm and rate control, studies suggest that quality of life may be significantly improved with ablation as compared to antiarrhythmic drugs.21 This may be because ablation may reduce AF‐related symptoms.12 As ablation becomes more widespread and recommended, physicians, including hospitalists, may be increasingly likely to refer their patients for ablation, even for patient subgroups who were not well‐represented in clinical trial settings.

The inpatient mortality rate in patients undergoing ablation therapy was quite low in our study, although ablation is not without some risk of procedure‐related stroke and other complications.19 An analysis of the compiled studies on ablation for AF estimates that major complication such as cardiac tamponade or thromboembolism occur in as many as 7% of patients.26 Patients are at highest risk for embolic events, such as transient ischemic attacks or ischemic strokes, in the immediate hours to weeks after ablation. An estimated 5% to 25% of patients will develop a new arrhythmia at some point in the postablation period and other complications, including esophageal injury, phrenic nerve injury, groin hematoma, and retroperitoneal bleed, have been observed.26 Increasing comanagement of postablation patients will necessitate that hospitalists understand the potential complications of ablation as well as current strategies for bridging anticoagulation therapy.

Few data are available about the safety and efficacy of catheter ablation for patients over the age of 65 years. In fact, the mean age of patients enrolled in most clinical trials of catheter ablation was younger than 60 years.26, 29 There are also limited data about the long‐term efficacy of ablation therapy in patients with structural heart disease30; despite this, our study shows that a quarter of patients with AF undergoing ablation therapy in the United States have diagnosed heart failure. As always, the optimistic introduction of new technologies to unstudied patient populations carries the risk of unintended harm. Hospitalists are well situated to collect and analyze outcome data for older patients with multiple comorbidities and to provide real‐time monitoring of potential complications.

Few studies have focused on the demographic and comorbid characteristics of patients undergoing ablation for AF on a national level. One study examined characteristics of patients referred to a single academic center for AF ablation from 1999 to 2005 and found that referred patients have, over time, been older (mean age 47 years in 1999 versus 56 years in 2005), have more persistent AF, larger atria, and were more likely to have had a history of cardiomyopathy (0% in 1999 versus 16% in 2006).16 This study also reported that men were consistently more likely to be referred for ablation than women. These results are generally consistent with our findings.

Our study has several limitations. The exact indication and specific type of ablation were not available in the NHDS, and it is possible that the ablation procedure was for an arrhythmia other than AF. However, our analysis of the subset of patients who only had AF as a diagnosis yielded results similar to the full analysis. We were unable to assess specific efficacy or complication data, but mortality was low and patients tended to have short hospital stays. Because the NHDS samples random hospitalizations, it is possible that some patients were overrepresented in the database if they were repeatedly hospitalized in a single year. This could potentially bias our results toward an overestimate of the number of patients who receive ablation.

It remains unclear what proportion of AF ablation procedures occur in the outpatient versus inpatient setting. Inpatient versus outpatient status is not specified in the few single‐center ablation experiences reported in the literature,16 and the few trials reported are not reliable for determining practice in a nonstudy setting. The most recent (2006) Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society Expert Consensus Statement on Catheter and Surgical Ablation of AF recommends aggressive anticoagulation in the periprocedure period with either heparin or low‐molecular‐weight heparins, followed by a bridge to warfarin.17 It makes intuitive sense that patients undergoing ablation for AF would be admitted at least overnight to bridge anticoagulation therapy and monitor for complications, but widespread use of low‐molecular‐weight heparin may make hospitalization less necessary. The observation that patients undergoing ablation had shorter hospital stays does not necessarily imply that ablation procedures shorten hospital stays. Rather, the data almost certainly reflect the fact that ablations are mostly elective procedures performed in the setting of planned short‐term admissions.

Our study provides important epidemiologic data about national trends in the use of ablation therapy in hospitalized patients with AF. We find that the rate of catheter ablation in patients with AF has been increasing significantly over time and across all age groups, including the oldest patients. As the proportion of patients with AF who receive ablation therapy continues to increase over time, comprehensive long‐term outcome data and cost‐effectiveness analyses will be important.

Atrial fibrillation (AF), the most common clinically significant cardiac arrhythmia, affects over 2.3 million people in the United States.1 AF is associated with an increased risk of stroke and heart failure and independently increases the risk of all cause mortality.26 As such, AF confers a staggering healthcare cost burden.7, 8 Pharmacologic treatments to restore sinus rhythm in patients with AF are associated with a considerable relapse rate911 and the development of nonpharmacologic treatments for AF, such as catheter ablation procedures,1214 may be significantly more successful in restoring and maintaining sinus rhythm.15, 16 Despite relatively poor results from early catheter ablation techniques, the practice has evolved and boasts short‐term success rates as high as 73% to 91% depending on the specific type of procedure.17

In light of the success of ablative therapy, this approach, which was once used primarily in younger patients with structurally intact hearts, has been expanded to include more medically complex patients, including elderly patients, those with cardiomyopathy, and those with implanted devices.16, 18 At the same time, catheter ablation is not without complications, with major complications observed in up to 6% of cases,19 and significant costs.20 Moreover, while the most optimistic randomized control data demonstrate the ability of catheter ablation to prevent the recurrence of AF at 1 year,12, 21, 22 long‐term outcome data are lacking, particularly in patients older than 65 years or those with heart failure.17, 23

The encouraging results supporting catheter ablation continue to stimulate the utilization of catheter ablation practices and spur innovations in ablation techniques.24 The American College of Cardiology/American Heart Association/European Society of Cardiology consensus guidelines recommend consideration of ablative therapy in many instances of AF.17 AF is primarily a disease of older adults25 and although most studies have focused on younger individuals,26 it is possible that increasing numbers of older patients are receiving ablation therapy.16 Although single center studies are available,16 there are few data about the characteristics of patients undergoing ablative therapy on a national level. In order to better understand the current use of catheter ablation treatment for AF, we analyzed data from the National Hospital Discharge Survey (NHDS) to explore trends in patient characteristics and rates of ablation procedures in hospitalized patients with AF from the years 1990 to 2005.

Methods

The NHDS is a nationally representative study of hospitalized patients conducted annually by the National Center for Health Statistics,27 which collects data from approximately 270,000 inpatient records using a representative sample of about 500 short‐stay nonfederal hospitals in the United States. Data for each patient are obtained for age, sex, hospital geographic region (Northeast, Midwest, South, West), and hospital bed size, as well as up to 7 diagnostic codes and 4 procedural codes using the International Classification of Diseases, 9th Revision, Clinical Modification (ICD‐9‐CM). Of note, data on race/ethnicity were not consistently coded in the NHDS and are therefore not included in this analysis.

We searched for all patients age 18 years or older who had an ICD‐9‐CM diagnosis of AF (427.31). Of these patients, we then identified those who had a procedure code for nonsurgical ablation of lesions or tissues of the heart via peripherally‐inserted catheter or an endovascular approach (37.34). We also searched for specific ICD‐9‐CM‐coded diagnoses corresponding to higher stroke risk according to the (CHADS₂) risk index,28 where 1 point is assigned for congestive heart failure, hypertension, age >75 years, or diabetes mellitus, and 2 points for prior stroke or transient ischemic attack. We calculated a CHADS₂ score for each patient.

Results

From 1990 to 2005, we identified 269,471 hospitalizations in the NHDS with a diagnosis of AF, of which 1,144 (0.42%) had a procedure code for catheter ablation. When extrapolated to national estimates, this corresponds to 32 million hospitalizations of patients with AF in the United States during the time period, of which 133,003 underwent ablation. The proportion of patients with AF who had ablation increased significantly over time, from 0.06% in 1990 to 0.79% in 2005 (P < 0.001 for trend; Figure 1).

Figure 1

On univariate analysis, people with AF undergoing ablation were on average younger and more likely to be male than those who did not have ablation (Table 1). The rate of catheter ablation was higher in patients younger than 50 years (1.75%) compared to 0.55% in patients aged 50 to 79 years, and 0.16% in patients aged 80 years or older. However, ablation rates increased significantly in all age groups over time, with no one age group increasing at a significantly faster rate than the others (P value for interaction between age categories and hospitalization year = 0.7; Figure 2). People undergoing ablation tended to have lower CHADS₂ stroke risk scores and fewer risk factors for stroke, including heart failure, coronary artery disease, and diabetes mellitus (Table 1).

Figure 2

People who underwent ablation were more likely to have private insurance as their primary source of payment and less likely to have Medicare (Table 1). Ablation rates were higher among patients with AF hospitalized in the Western and Southern regions of the United States (0.52% and 0.53%, respectively), compared to rates in the Midwest (0.30%) and Northeast (0.40%). Hospital bed‐size was significantly related to the frequency of ablation, with the overall rate of ablation in patients with AF being 0.04% in hospitals with 6 to 99 beds compared to 1.37% in hospitals with at least 500 beds (P < 0.001). Length of stay was shorter in patients with ablations compared to patients without ablation therapy, and patients with ablation were more likely to be discharged home (Table 1). The inpatient mortality rate in patients undergoing ablation was quite low (0.96%).

In multivariate analysis, the likelihood of ablation therapy in a hospitalized patient with AF increased by 15% per year (95% confidence interval [CI], 13%‐16%) over the time period, adjusted for clinical and hospital characteristics. The likelihood of ablation decreased with older age (adjusted odds ratio [aOR], 0.7 [95% CI, 0.6‐0.7] for each decade of age over 50 years) and for each 1‐point increase in CHADS₂ score (aOR, 0.7 [95% CI, 0.7‐0.8]). Ablation was significantly more likely to be performed in hospitals with larger bed‐sizes (aOR, 27.4 [95% CI, 16.1‐46.6] comparing bed‐size of 500+ to bed‐size of 6 to 99) and in patients with private insurance (aOR, 1.4 [95% CI, 1.2‐1.6]; Table 2). The goodness‐of‐fit of the model was appropriate, with a nonsignificant Hosmer‐Lemeshow test P value of 0.13.

To account for the possibility that the ablation procedure was not specifically for AF, we performed a subgroup analysis that excluded all patients who also had diagnostic codes for supraventricular or ventricular tachycardias (427.0, 427.1, 427.2, and 427.4), or atrial flutter (427.32). Of the 269,471 hospitalizations with AF, 23,069 (8.6%) had a code for an arrhythmia in addition to AF. When we excluded patients with other arrhythmias, we identified 691 patients who underwent ablation and who only had a diagnosis of AF. An analysis of this subset yielded results similar to the full analysis (Table 2). The likelihood of ablation therapy in this subset of patients with only AF increased by 14% per year (95% CI, 11%‐16%), adjusting for patient age, sex, insurance status, CHADS₂ score, hospital region, and hospital bed‐size.

Discussion

The proportion of hospitalized patients with AF who undergo ablation therapy in the United States has been increasing by approximately 15% per year over the last 15 years. Patients receiving ablation therapy are more likely to be younger, have private insurance, and have fewer stroke risk factors. These demographics likely reflect the fact that these ablations are elective procedures that are preferentially performed in healthier, lower‐risk patients. Despite these preferences, the rate of ablation therapy has been increasing significantly across all age groups, even in the oldest patients.

Though limited by relatively short follow‐up data, published studies of ablation therapies for AF show promising results,17, 26 and initial cost analyses suggest possible fiscal benefits of ablation for AF.20 Despite a paucity of randomized clinical trials comparing ablation to pharmacologic rhythm and rate control, studies suggest that quality of life may be significantly improved with ablation as compared to antiarrhythmic drugs.21 This may be because ablation may reduce AF‐related symptoms.12 As ablation becomes more widespread and recommended, physicians, including hospitalists, may be increasingly likely to refer their patients for ablation, even for patient subgroups who were not well‐represented in clinical trial settings.

The inpatient mortality rate in patients undergoing ablation therapy was quite low in our study, although ablation is not without some risk of procedure‐related stroke and other complications.19 An analysis of the compiled studies on ablation for AF estimates that major complication such as cardiac tamponade or thromboembolism occur in as many as 7% of patients.26 Patients are at highest risk for embolic events, such as transient ischemic attacks or ischemic strokes, in the immediate hours to weeks after ablation. An estimated 5% to 25% of patients will develop a new arrhythmia at some point in the postablation period and other complications, including esophageal injury, phrenic nerve injury, groin hematoma, and retroperitoneal bleed, have been observed.26 Increasing comanagement of postablation patients will necessitate that hospitalists understand the potential complications of ablation as well as current strategies for bridging anticoagulation therapy.

Few data are available about the safety and efficacy of catheter ablation for patients over the age of 65 years. In fact, the mean age of patients enrolled in most clinical trials of catheter ablation was younger than 60 years.26, 29 There are also limited data about the long‐term efficacy of ablation therapy in patients with structural heart disease30; despite this, our study shows that a quarter of patients with AF undergoing ablation therapy in the United States have diagnosed heart failure. As always, the optimistic introduction of new technologies to unstudied patient populations carries the risk of unintended harm. Hospitalists are well situated to collect and analyze outcome data for older patients with multiple comorbidities and to provide real‐time monitoring of potential complications.

Few studies have focused on the demographic and comorbid characteristics of patients undergoing ablation for AF on a national level. One study examined characteristics of patients referred to a single academic center for AF ablation from 1999 to 2005 and found that referred patients have, over time, been older (mean age 47 years in 1999 versus 56 years in 2005), have more persistent AF, larger atria, and were more likely to have had a history of cardiomyopathy (0% in 1999 versus 16% in 2006).16 This study also reported that men were consistently more likely to be referred for ablation than women. These results are generally consistent with our findings.

Our study has several limitations. The exact indication and specific type of ablation were not available in the NHDS, and it is possible that the ablation procedure was for an arrhythmia other than AF. However, our analysis of the subset of patients who only had AF as a diagnosis yielded results similar to the full analysis. We were unable to assess specific efficacy or complication data, but mortality was low and patients tended to have short hospital stays. Because the NHDS samples random hospitalizations, it is possible that some patients were overrepresented in the database if they were repeatedly hospitalized in a single year. This could potentially bias our results toward an overestimate of the number of patients who receive ablation.

It remains unclear what proportion of AF ablation procedures occur in the outpatient versus inpatient setting. Inpatient versus outpatient status is not specified in the few single‐center ablation experiences reported in the literature,16 and the few trials reported are not reliable for determining practice in a nonstudy setting. The most recent (2006) Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society Expert Consensus Statement on Catheter and Surgical Ablation of AF recommends aggressive anticoagulation in the periprocedure period with either heparin or low‐molecular‐weight heparins, followed by a bridge to warfarin.17 It makes intuitive sense that patients undergoing ablation for AF would be admitted at least overnight to bridge anticoagulation therapy and monitor for complications, but widespread use of low‐molecular‐weight heparin may make hospitalization less necessary. The observation that patients undergoing ablation had shorter hospital stays does not necessarily imply that ablation procedures shorten hospital stays. Rather, the data almost certainly reflect the fact that ablations are mostly elective procedures performed in the setting of planned short‐term admissions.

Our study provides important epidemiologic data about national trends in the use of ablation therapy in hospitalized patients with AF. We find that the rate of catheter ablation in patients with AF has been increasing significantly over time and across all age groups, including the oldest patients. As the proportion of patients with AF who receive ablation therapy continues to increase over time, comprehensive long‐term outcome data and cost‐effectiveness analyses will be important.

Diabetes mellitus (DM) is a common chronic disease with a long downward course and serious systemic consequences. The percentage of the population with diagnosed diabetes continues to rise. In 2007, more than 246 million people had diabetes worldwide.1 In the United States, the diabetes rate was 5.8% in 2007, and is estimated to rise to 12% by 2050.2, 3 Many factors may contribute to this rise in the prevalence of diabetes, including higher prevalence of overweight and obesity, unhealthy diet, sedentary lifestyle, changes in diagnostic criteria, improved detection methods, decreasing mortality, a growing elderly population, and growth in minority populations with predisposition to diabetes; (ie, African Americans, Hispanics, and Native Americans).1, 4, 5 This is consistent with the thrifty genotype hypothesis, which explains the morbid prevalence of obesity, diabetes, and atherosclerosis‐related complications in modern times.6

The total estimated cost of diabetes in 2007 was $174 billion, including $116 billion in excess medical expenditures ($27 billion for direct diabetes care, $58 billion for treatment of diabetes‐related chronic complications, and $31 billion in excess general medical costs) and $58 billion in reduced national productivity.7 The largest component of medical expenditures that is attributed to diabetes has been hospital inpatient care (50% of total cost).8

Spine surgery is expensive and any factor that influences cost of surgery merits meticulous study, especially with the financial difficulties that the healthcare system is facing. Diabetic patients are known to be more vulnerable to postoperative complications such as fever, wound infection, foot drop, and nonunion than their nondiabetic peers.9‐13 In diabetic spine surgery patients, a negative correlation was reported between the recovery rate and the preoperative glycosylated hemoglobin (HbA1c) level.14 However, the potential impact of undiagnosed diabetes on these variables have not yet been extensively studied. In order to determine the prevalence of explicit DM and undiagnosed elevation of HBA1c among spine surgery patients and its impact on healthcare cost, we conducted the following study.

Patients and Methods

We retrospectively reviewed the charts of 556 spine surgery patients who were operated on between 2005 and 2007 and had 1 of 3 types of surgery: lumbar microdiscectomy (LMD), anterior cervical decompression and fusion (ACDF), and lumbar decompression and fusion (LDF). Information was collected about their diabetes history, HbA1c level, age, race, body mass index (BMI), comorbidities, length of stay (LOS), and total cost (hospital and physician). Due to the high percentage of glucose metabolism disturbance in the population and the many reports of increased postoperative complications related to diabetes, patients are routinely seen by an internist on the preoperative visit and they undergo electrocardiography and laboratory testing, including HbA1c. Hence HbA1c was recorded for 456 patients. We used 6.1% as a screening cutpoint for high HbA1c and classified patients to 4 groups according to their DM‐HbA1c status:15

• 1

  Those with history of DM and HbA1c 6.1% (DM);

• 2

  Those without history of DM and HbA1c 6.1% (subclinical HbA1c elevation);

• 3

  Those with history of DM and HbA1c < 6.1% (well‐controlled DM);

• 4

  Those without history of DM and HbA1c < 6.1% (no DM).

The second group was our main group of interest (subclinical, previously unknown HbA1c elevation). The third group (patients with well‐controlled DM, which is uncommon) was excluded (n = 14). To prevent confusion in the coming text, mentioning elevation of HbA1c will imply the second group, while the term diabetes will refer to the first group.

We calculated the percentages of nondiabetic patients, those with subclinical HbA1c elevation, and those with already known DM. We computed the mean (m) and standard deviation (SD) for cost, age, and BMI. Using SPSS v.16 (SPSS, Chicago, IL) we applied the analysis of covariance (ANCOVA) to determine the impact of DM‐HbA1c on total healthcare cost after controlling for type of surgery. We used analysis of variance (ANOVA) and post hoc Scheffe test to check for any significant differences in healthcare cost (hospital and surgery costs), age, gender, race, and BMI between the three DM‐HbA1c groups. Finally, we applied regression analysis to figure out significant factors/predictors of total cost in spine surgery patients beside type of surgery.

Results

After excluding the third group, we had 442 spine surgery patients, 26.7% LMD, 49.1% ACDF, and 24.2% LDF. They were 21‐92 years of age (over 60 years old = 41%), and nearly equally divided according to gender (48.2% males). They were mostly Caucasian (78.3% Caucasians and 21% African Americans). There were no Hispanics in the sample, which may be due to the small proportion of the Latino population living in Macon, GA.

Calculations showed that 72.4% of the above patients were nondiabetic, 14.3% were subclinical patients with elevated HbA1c, and 13.3% were already known, confirmed DM patients. Results showed that elevation of HbA1c was highest and diabetes was lowest in the LDF group, 16% and 10%, respectively. On the contrary, elevation of HbA1c was lowest and diabetes was highest in the LMD group, 13% and 20%, respectively (Figure 1).

Figure 1

While analyzing the data, we took into consideration that the main cost‐determining factor was type of surgery (P < 0.001), so the pure impact of the DM‐HbA1c status on total cost was elicited by using ANCOVA and including type of surgery as a covariate. Table 1 shows the total cost for spine surgery patients per type of surgery and DM‐HbA1c status.

As evident in Table 1 and confirmed by statistical analysis, DM‐HbA1c status was a very significant determinant (P < 0.01) of total cost. We performed ANOVA in each surgical category to determine the significance of differences in total cost between DM‐HbA1c status groups. There were significant differences in the LDF group between the no DM and subclinical groups (P < 0.05) in terms of cost and LOS, and in the ACDF group between patients without DM and those with already known DM in cost (P < 0.05). Figures 2 and 3 summarize the results mentioned above.

Figure 2

Figure 3

As expected, age (P < 0.001) and BMI (P 0.01) were significantly different between DM‐HbA1c groups. Scheffe test showed significant difference between no DM and DM (P < 0.001) groups and between subclinical and DM groups (P < 0.01) regarding age and between no DM and DM groups (P < 0.05) regarding BMI. There was no difference (P > 0.05) between the three DM‐HbA1c groups regarding type of surgery. The subclinical patients with HbA1c elevation appeared to be as old as nondiabetic patients (P = 0.669) but as heavy as diabetic patients (P = 1.000).

The range of BMI in the sample was 17 to 52 with 36% over 30; (ie, obese) (Table 2). Regression analysis showed that type of surgery, age, and BMI were very significant predictors of total cost in spine surgery patients (P 0.001). In our study, total cost was not dependent on sex or race. Repeating analysis with age, BMI, or both as covariates (ANCOVA) deprives DM‐HbA1c status of statistical significance (P > 0.05).

Concerning comorbidities that could affect HbA1c level, only 1.4% of patients had a history of advanced or chronic renal disease and none had hemoglobinopathy.

Discussion

According to the Centers for Disease Control and Prevention (CDC), approximately 54 million people in the United States have prediabetes and nearly 21 million have diabetes.3 This places almost 25% of the population at risk for diabetic complications. Prediabetes is a term used to distinguish people who are at increased risk of developing diabetes. People with prediabetes have impaired fasting glucose (100‐125 mg/dL), impaired glucose tolerance (140‐199 mg/dL at 2 hours), or both.16 The actual national burden of diabetes most likely exceeds the $174 billion estimate because of excess medical costs associated with prediabetic patients.

Due to the impracticality of the 2 tests mentioned above as screening methods for diabetes and prediabetes, we used HbA1c to screen for glucose metabolism disturbance. This marker does not need overnight fasting or a 2‐hour glucose loading test. The HbA1c level gives an average of glycemic control over the previous 120 days, as red blood cells have a lifespan of 120 days. Although the use of HbA1c for the diagnosis of diabetes is not yet established, its availability at the time when the patient is seen (point‐of‐care testing) is a great advantage over fasting glucose and glucose tolerance tests.17, 18 The normal range for a person without diabetes is 4.3% to 5.9%.19 For most people with diabetes the American Diabetes Association recommends targeting an HbA1c of 7% or less. If HbA1c is 8% or higher, it means that the patient's blood glucose is not well‐controlled and he/she is at increased risk for developing diabetic complications. In this case, the patient needs modifications in his/her diet, physical activity, oral hypoglycemic medications, or insulin. It is uncommon to have patients with a history of diabetes and HbA1c < 6.1%. Our patient sample confirms this fact (n = 14). Therefore, it was not included in the statistical analysis.

The cutpoint 6.1% (2 SD above the mean) was the recommended cutoff point for HbA1c in most reviewed studies.15, 20 At the Diabetes Control and Complications Trial and Prospective Diabetes Study, the sensitivity of this cutpoint in detecting diabetes was 78% to 81% and specificity was 79% to 84%.15 HbA1c was shown to have less intraindividual variation and better predicts both microvascular and macrovascular complications.15 Although the current cost of HbA1c is higher than fasting plasma glucose, its feasibility as a screening tool for DM and as a predictor of its costly preventable complications may make it a cost‐effective choice.

Unrecognized glycometabolic disturbance as measured by HbA1c have recently been associated with poor outcomes, for example, after acute myocardial infarction.21 Postoperative complications in diabetic patients have been attributed to impairments in the immune system and microangiopathy. Patients with poorly regulated glucose levels are at an increased risk for developing infections. Once a person with diabetes has developed an infection, the body is less capable of fighting it off because high glucose levels interfere with the normal function of white blood cells. Moreover, dysfunction in the immune system impairs the inflammatory reaction in local tissues, which is further aggravated by the reduced blood supply due to diabetic microangiopathy. This results in considerable increase in the risk of soft‐tissue complications and significant delays in wound and bone healing.22

Our patient sample was classified according to chart and laboratory findings. The two criteria we used to classify them were a history of diabetes and HbA1c level 6.1%. Results show that patients unaware about their elevated HbA1c level are almost equal to the percentage of patients with history of diabetes. Combined, they make slightly more than 25% of spine surgery patients. These results are consistent with the CDC's estimate of the percentage of diabetes and prediabetes in the general population.3 Further analysis shows that age and BMI are significantly different between DM‐HbA1c groups, which is unsurprising since the correlation of diabetes with age and BMI is well‐established.23 Interestingly, the subclinical patients with elevated HbA1c appear to be as old as nondiabetic patients but as heavy as their diabetic peers. This is a remarkable finding that reflects the transitional status of these patients between non‐diabetes and diabetes. In addition, age and BMI were found to be very significant determinants of total cost in spine surgery patients. Actually, they were the reasons behind the statistical significance shown by the DM‐HbA1c status regarding cost as exposed by the ANCOVA.

This middle category of spine surgery patients with subclinical glucose metabolism disturbance seems to have important economic implications in terms of LOS and total cost in the LDF group. This may be due to the larger share of this middle subgroup in the LDF group of patients, as shown above. Besides, LDF patients stay longer and cost more than other spine surgery patients and consequently statistical differences between DM‐HbA1c subgroups are more evident. LDF is major surgery, with extensive dissection, greater blood loss, and longer operative time than other types of spine surgery and the patients are older and sicker. That may be why there was a more pronounced difference in LOS and cost between its 3 subgroups.

Overall, this work expands upon our understanding of the importance of diabetes and undiagnosed elevation of HbA1c in affecting cost following surgery. However, the study has several limitations that should be taken into consideration. Potential underreporting of diabetes in the patient's chart could skew the results, although this was unlikely due to the repetitive interview of patients on multiple occasions. In addition, HbA1c level could be affected by prescribed medications, which were not included in our inquiries. LOS and cost could also be influenced by non‐diabetes‐related factors that were not considered in the study. Finally, a bigger sample would have given more power to the results, although 556 patients is, without a doubt, not a small group.

Conclusions

There is a significant segment of spine surgery patients who learn of their disturbed glucose metabolism status for the first time on their preoperative visit. These patients require further investigation, with a fasting glucose test to confirm their diabetes status, and they need to start treatment early to prevent future complications.

HbA1c testing should be considered in the routine preoperative workup of spine surgery patients. This is a simple point‐of‐care test and its results can be obtained without delay. This will help improve early diagnosis of prediabetes and diabetes and may prevent the onset of type 2 diabetes, thus improving the patient's health and final outcome.

We need continuing research into the healthcare costs of diabetic patients in different medical specialties, as this will improve awareness about the economic impact and cost‐effectiveness issues related to this prevalent disease.

Diabetes mellitus (DM) is a common chronic disease with a long downward course and serious systemic consequences. The percentage of the population with diagnosed diabetes continues to rise. In 2007, more than 246 million people had diabetes worldwide.1 In the United States, the diabetes rate was 5.8% in 2007, and is estimated to rise to 12% by 2050.2, 3 Many factors may contribute to this rise in the prevalence of diabetes, including higher prevalence of overweight and obesity, unhealthy diet, sedentary lifestyle, changes in diagnostic criteria, improved detection methods, decreasing mortality, a growing elderly population, and growth in minority populations with predisposition to diabetes; (ie, African Americans, Hispanics, and Native Americans).1, 4, 5 This is consistent with the thrifty genotype hypothesis, which explains the morbid prevalence of obesity, diabetes, and atherosclerosis‐related complications in modern times.6

The total estimated cost of diabetes in 2007 was $174 billion, including $116 billion in excess medical expenditures ($27 billion for direct diabetes care, $58 billion for treatment of diabetes‐related chronic complications, and $31 billion in excess general medical costs) and $58 billion in reduced national productivity.7 The largest component of medical expenditures that is attributed to diabetes has been hospital inpatient care (50% of total cost).8

Spine surgery is expensive and any factor that influences cost of surgery merits meticulous study, especially with the financial difficulties that the healthcare system is facing. Diabetic patients are known to be more vulnerable to postoperative complications such as fever, wound infection, foot drop, and nonunion than their nondiabetic peers.9‐13 In diabetic spine surgery patients, a negative correlation was reported between the recovery rate and the preoperative glycosylated hemoglobin (HbA1c) level.14 However, the potential impact of undiagnosed diabetes on these variables have not yet been extensively studied. In order to determine the prevalence of explicit DM and undiagnosed elevation of HBA1c among spine surgery patients and its impact on healthcare cost, we conducted the following study.

Patients and Methods

We retrospectively reviewed the charts of 556 spine surgery patients who were operated on between 2005 and 2007 and had 1 of 3 types of surgery: lumbar microdiscectomy (LMD), anterior cervical decompression and fusion (ACDF), and lumbar decompression and fusion (LDF). Information was collected about their diabetes history, HbA1c level, age, race, body mass index (BMI), comorbidities, length of stay (LOS), and total cost (hospital and physician). Due to the high percentage of glucose metabolism disturbance in the population and the many reports of increased postoperative complications related to diabetes, patients are routinely seen by an internist on the preoperative visit and they undergo electrocardiography and laboratory testing, including HbA1c. Hence HbA1c was recorded for 456 patients. We used 6.1% as a screening cutpoint for high HbA1c and classified patients to 4 groups according to their DM‐HbA1c status:15

• 1

  Those with history of DM and HbA1c 6.1% (DM);

• 2

  Those without history of DM and HbA1c 6.1% (subclinical HbA1c elevation);

• 3

  Those with history of DM and HbA1c < 6.1% (well‐controlled DM);

• 4

  Those without history of DM and HbA1c < 6.1% (no DM).

The second group was our main group of interest (subclinical, previously unknown HbA1c elevation). The third group (patients with well‐controlled DM, which is uncommon) was excluded (n = 14). To prevent confusion in the coming text, mentioning elevation of HbA1c will imply the second group, while the term diabetes will refer to the first group.

We calculated the percentages of nondiabetic patients, those with subclinical HbA1c elevation, and those with already known DM. We computed the mean (m) and standard deviation (SD) for cost, age, and BMI. Using SPSS v.16 (SPSS, Chicago, IL) we applied the analysis of covariance (ANCOVA) to determine the impact of DM‐HbA1c on total healthcare cost after controlling for type of surgery. We used analysis of variance (ANOVA) and post hoc Scheffe test to check for any significant differences in healthcare cost (hospital and surgery costs), age, gender, race, and BMI between the three DM‐HbA1c groups. Finally, we applied regression analysis to figure out significant factors/predictors of total cost in spine surgery patients beside type of surgery.

Results

After excluding the third group, we had 442 spine surgery patients, 26.7% LMD, 49.1% ACDF, and 24.2% LDF. They were 21‐92 years of age (over 60 years old = 41%), and nearly equally divided according to gender (48.2% males). They were mostly Caucasian (78.3% Caucasians and 21% African Americans). There were no Hispanics in the sample, which may be due to the small proportion of the Latino population living in Macon, GA.

Calculations showed that 72.4% of the above patients were nondiabetic, 14.3% were subclinical patients with elevated HbA1c, and 13.3% were already known, confirmed DM patients. Results showed that elevation of HbA1c was highest and diabetes was lowest in the LDF group, 16% and 10%, respectively. On the contrary, elevation of HbA1c was lowest and diabetes was highest in the LMD group, 13% and 20%, respectively (Figure 1).

Figure 1

While analyzing the data, we took into consideration that the main cost‐determining factor was type of surgery (P < 0.001), so the pure impact of the DM‐HbA1c status on total cost was elicited by using ANCOVA and including type of surgery as a covariate. Table 1 shows the total cost for spine surgery patients per type of surgery and DM‐HbA1c status.

As evident in Table 1 and confirmed by statistical analysis, DM‐HbA1c status was a very significant determinant (P < 0.01) of total cost. We performed ANOVA in each surgical category to determine the significance of differences in total cost between DM‐HbA1c status groups. There were significant differences in the LDF group between the no DM and subclinical groups (P < 0.05) in terms of cost and LOS, and in the ACDF group between patients without DM and those with already known DM in cost (P < 0.05). Figures 2 and 3 summarize the results mentioned above.

Figure 2

Figure 3

As expected, age (P < 0.001) and BMI (P 0.01) were significantly different between DM‐HbA1c groups. Scheffe test showed significant difference between no DM and DM (P < 0.001) groups and between subclinical and DM groups (P < 0.01) regarding age and between no DM and DM groups (P < 0.05) regarding BMI. There was no difference (P > 0.05) between the three DM‐HbA1c groups regarding type of surgery. The subclinical patients with HbA1c elevation appeared to be as old as nondiabetic patients (P = 0.669) but as heavy as diabetic patients (P = 1.000).

The range of BMI in the sample was 17 to 52 with 36% over 30; (ie, obese) (Table 2). Regression analysis showed that type of surgery, age, and BMI were very significant predictors of total cost in spine surgery patients (P 0.001). In our study, total cost was not dependent on sex or race. Repeating analysis with age, BMI, or both as covariates (ANCOVA) deprives DM‐HbA1c status of statistical significance (P > 0.05).

Concerning comorbidities that could affect HbA1c level, only 1.4% of patients had a history of advanced or chronic renal disease and none had hemoglobinopathy.

Discussion

According to the Centers for Disease Control and Prevention (CDC), approximately 54 million people in the United States have prediabetes and nearly 21 million have diabetes.3 This places almost 25% of the population at risk for diabetic complications. Prediabetes is a term used to distinguish people who are at increased risk of developing diabetes. People with prediabetes have impaired fasting glucose (100‐125 mg/dL), impaired glucose tolerance (140‐199 mg/dL at 2 hours), or both.16 The actual national burden of diabetes most likely exceeds the $174 billion estimate because of excess medical costs associated with prediabetic patients.

Due to the impracticality of the 2 tests mentioned above as screening methods for diabetes and prediabetes, we used HbA1c to screen for glucose metabolism disturbance. This marker does not need overnight fasting or a 2‐hour glucose loading test. The HbA1c level gives an average of glycemic control over the previous 120 days, as red blood cells have a lifespan of 120 days. Although the use of HbA1c for the diagnosis of diabetes is not yet established, its availability at the time when the patient is seen (point‐of‐care testing) is a great advantage over fasting glucose and glucose tolerance tests.17, 18 The normal range for a person without diabetes is 4.3% to 5.9%.19 For most people with diabetes the American Diabetes Association recommends targeting an HbA1c of 7% or less. If HbA1c is 8% or higher, it means that the patient's blood glucose is not well‐controlled and he/she is at increased risk for developing diabetic complications. In this case, the patient needs modifications in his/her diet, physical activity, oral hypoglycemic medications, or insulin. It is uncommon to have patients with a history of diabetes and HbA1c < 6.1%. Our patient sample confirms this fact (n = 14). Therefore, it was not included in the statistical analysis.

The cutpoint 6.1% (2 SD above the mean) was the recommended cutoff point for HbA1c in most reviewed studies.15, 20 At the Diabetes Control and Complications Trial and Prospective Diabetes Study, the sensitivity of this cutpoint in detecting diabetes was 78% to 81% and specificity was 79% to 84%.15 HbA1c was shown to have less intraindividual variation and better predicts both microvascular and macrovascular complications.15 Although the current cost of HbA1c is higher than fasting plasma glucose, its feasibility as a screening tool for DM and as a predictor of its costly preventable complications may make it a cost‐effective choice.

Unrecognized glycometabolic disturbance as measured by HbA1c have recently been associated with poor outcomes, for example, after acute myocardial infarction.21 Postoperative complications in diabetic patients have been attributed to impairments in the immune system and microangiopathy. Patients with poorly regulated glucose levels are at an increased risk for developing infections. Once a person with diabetes has developed an infection, the body is less capable of fighting it off because high glucose levels interfere with the normal function of white blood cells. Moreover, dysfunction in the immune system impairs the inflammatory reaction in local tissues, which is further aggravated by the reduced blood supply due to diabetic microangiopathy. This results in considerable increase in the risk of soft‐tissue complications and significant delays in wound and bone healing.22

Our patient sample was classified according to chart and laboratory findings. The two criteria we used to classify them were a history of diabetes and HbA1c level 6.1%. Results show that patients unaware about their elevated HbA1c level are almost equal to the percentage of patients with history of diabetes. Combined, they make slightly more than 25% of spine surgery patients. These results are consistent with the CDC's estimate of the percentage of diabetes and prediabetes in the general population.3 Further analysis shows that age and BMI are significantly different between DM‐HbA1c groups, which is unsurprising since the correlation of diabetes with age and BMI is well‐established.23 Interestingly, the subclinical patients with elevated HbA1c appear to be as old as nondiabetic patients but as heavy as their diabetic peers. This is a remarkable finding that reflects the transitional status of these patients between non‐diabetes and diabetes. In addition, age and BMI were found to be very significant determinants of total cost in spine surgery patients. Actually, they were the reasons behind the statistical significance shown by the DM‐HbA1c status regarding cost as exposed by the ANCOVA.

This middle category of spine surgery patients with subclinical glucose metabolism disturbance seems to have important economic implications in terms of LOS and total cost in the LDF group. This may be due to the larger share of this middle subgroup in the LDF group of patients, as shown above. Besides, LDF patients stay longer and cost more than other spine surgery patients and consequently statistical differences between DM‐HbA1c subgroups are more evident. LDF is major surgery, with extensive dissection, greater blood loss, and longer operative time than other types of spine surgery and the patients are older and sicker. That may be why there was a more pronounced difference in LOS and cost between its 3 subgroups.

Overall, this work expands upon our understanding of the importance of diabetes and undiagnosed elevation of HbA1c in affecting cost following surgery. However, the study has several limitations that should be taken into consideration. Potential underreporting of diabetes in the patient's chart could skew the results, although this was unlikely due to the repetitive interview of patients on multiple occasions. In addition, HbA1c level could be affected by prescribed medications, which were not included in our inquiries. LOS and cost could also be influenced by non‐diabetes‐related factors that were not considered in the study. Finally, a bigger sample would have given more power to the results, although 556 patients is, without a doubt, not a small group.

Conclusions

There is a significant segment of spine surgery patients who learn of their disturbed glucose metabolism status for the first time on their preoperative visit. These patients require further investigation, with a fasting glucose test to confirm their diabetes status, and they need to start treatment early to prevent future complications.

HbA1c testing should be considered in the routine preoperative workup of spine surgery patients. This is a simple point‐of‐care test and its results can be obtained without delay. This will help improve early diagnosis of prediabetes and diabetes and may prevent the onset of type 2 diabetes, thus improving the patient's health and final outcome.

We need continuing research into the healthcare costs of diabetic patients in different medical specialties, as this will improve awareness about the economic impact and cost‐effectiveness issues related to this prevalent disease.

Diabetes mellitus (DM) is a common chronic disease with a long downward course and serious systemic consequences. The percentage of the population with diagnosed diabetes continues to rise. In 2007, more than 246 million people had diabetes worldwide.1 In the United States, the diabetes rate was 5.8% in 2007, and is estimated to rise to 12% by 2050.2, 3 Many factors may contribute to this rise in the prevalence of diabetes, including higher prevalence of overweight and obesity, unhealthy diet, sedentary lifestyle, changes in diagnostic criteria, improved detection methods, decreasing mortality, a growing elderly population, and growth in minority populations with predisposition to diabetes; (ie, African Americans, Hispanics, and Native Americans).1, 4, 5 This is consistent with the thrifty genotype hypothesis, which explains the morbid prevalence of obesity, diabetes, and atherosclerosis‐related complications in modern times.6

The total estimated cost of diabetes in 2007 was $174 billion, including $116 billion in excess medical expenditures ($27 billion for direct diabetes care, $58 billion for treatment of diabetes‐related chronic complications, and $31 billion in excess general medical costs) and $58 billion in reduced national productivity.7 The largest component of medical expenditures that is attributed to diabetes has been hospital inpatient care (50% of total cost).8

Spine surgery is expensive and any factor that influences cost of surgery merits meticulous study, especially with the financial difficulties that the healthcare system is facing. Diabetic patients are known to be more vulnerable to postoperative complications such as fever, wound infection, foot drop, and nonunion than their nondiabetic peers.9‐13 In diabetic spine surgery patients, a negative correlation was reported between the recovery rate and the preoperative glycosylated hemoglobin (HbA1c) level.14 However, the potential impact of undiagnosed diabetes on these variables have not yet been extensively studied. In order to determine the prevalence of explicit DM and undiagnosed elevation of HBA1c among spine surgery patients and its impact on healthcare cost, we conducted the following study.

Patients and Methods

We retrospectively reviewed the charts of 556 spine surgery patients who were operated on between 2005 and 2007 and had 1 of 3 types of surgery: lumbar microdiscectomy (LMD), anterior cervical decompression and fusion (ACDF), and lumbar decompression and fusion (LDF). Information was collected about their diabetes history, HbA1c level, age, race, body mass index (BMI), comorbidities, length of stay (LOS), and total cost (hospital and physician). Due to the high percentage of glucose metabolism disturbance in the population and the many reports of increased postoperative complications related to diabetes, patients are routinely seen by an internist on the preoperative visit and they undergo electrocardiography and laboratory testing, including HbA1c. Hence HbA1c was recorded for 456 patients. We used 6.1% as a screening cutpoint for high HbA1c and classified patients to 4 groups according to their DM‐HbA1c status:15

• 1

  Those with history of DM and HbA1c 6.1% (DM);

• 2

  Those without history of DM and HbA1c 6.1% (subclinical HbA1c elevation);

• 3

  Those with history of DM and HbA1c < 6.1% (well‐controlled DM);

• 4

  Those without history of DM and HbA1c < 6.1% (no DM).

The second group was our main group of interest (subclinical, previously unknown HbA1c elevation). The third group (patients with well‐controlled DM, which is uncommon) was excluded (n = 14). To prevent confusion in the coming text, mentioning elevation of HbA1c will imply the second group, while the term diabetes will refer to the first group.

We calculated the percentages of nondiabetic patients, those with subclinical HbA1c elevation, and those with already known DM. We computed the mean (m) and standard deviation (SD) for cost, age, and BMI. Using SPSS v.16 (SPSS, Chicago, IL) we applied the analysis of covariance (ANCOVA) to determine the impact of DM‐HbA1c on total healthcare cost after controlling for type of surgery. We used analysis of variance (ANOVA) and post hoc Scheffe test to check for any significant differences in healthcare cost (hospital and surgery costs), age, gender, race, and BMI between the three DM‐HbA1c groups. Finally, we applied regression analysis to figure out significant factors/predictors of total cost in spine surgery patients beside type of surgery.

Results

After excluding the third group, we had 442 spine surgery patients, 26.7% LMD, 49.1% ACDF, and 24.2% LDF. They were 21‐92 years of age (over 60 years old = 41%), and nearly equally divided according to gender (48.2% males). They were mostly Caucasian (78.3% Caucasians and 21% African Americans). There were no Hispanics in the sample, which may be due to the small proportion of the Latino population living in Macon, GA.

Calculations showed that 72.4% of the above patients were nondiabetic, 14.3% were subclinical patients with elevated HbA1c, and 13.3% were already known, confirmed DM patients. Results showed that elevation of HbA1c was highest and diabetes was lowest in the LDF group, 16% and 10%, respectively. On the contrary, elevation of HbA1c was lowest and diabetes was highest in the LMD group, 13% and 20%, respectively (Figure 1).

Figure 1

While analyzing the data, we took into consideration that the main cost‐determining factor was type of surgery (P < 0.001), so the pure impact of the DM‐HbA1c status on total cost was elicited by using ANCOVA and including type of surgery as a covariate. Table 1 shows the total cost for spine surgery patients per type of surgery and DM‐HbA1c status.

As evident in Table 1 and confirmed by statistical analysis, DM‐HbA1c status was a very significant determinant (P < 0.01) of total cost. We performed ANOVA in each surgical category to determine the significance of differences in total cost between DM‐HbA1c status groups. There were significant differences in the LDF group between the no DM and subclinical groups (P < 0.05) in terms of cost and LOS, and in the ACDF group between patients without DM and those with already known DM in cost (P < 0.05). Figures 2 and 3 summarize the results mentioned above.

Figure 2

Figure 3

As expected, age (P < 0.001) and BMI (P 0.01) were significantly different between DM‐HbA1c groups. Scheffe test showed significant difference between no DM and DM (P < 0.001) groups and between subclinical and DM groups (P < 0.01) regarding age and between no DM and DM groups (P < 0.05) regarding BMI. There was no difference (P > 0.05) between the three DM‐HbA1c groups regarding type of surgery. The subclinical patients with HbA1c elevation appeared to be as old as nondiabetic patients (P = 0.669) but as heavy as diabetic patients (P = 1.000).

The range of BMI in the sample was 17 to 52 with 36% over 30; (ie, obese) (Table 2). Regression analysis showed that type of surgery, age, and BMI were very significant predictors of total cost in spine surgery patients (P 0.001). In our study, total cost was not dependent on sex or race. Repeating analysis with age, BMI, or both as covariates (ANCOVA) deprives DM‐HbA1c status of statistical significance (P > 0.05).

Concerning comorbidities that could affect HbA1c level, only 1.4% of patients had a history of advanced or chronic renal disease and none had hemoglobinopathy.

Discussion

According to the Centers for Disease Control and Prevention (CDC), approximately 54 million people in the United States have prediabetes and nearly 21 million have diabetes.3 This places almost 25% of the population at risk for diabetic complications. Prediabetes is a term used to distinguish people who are at increased risk of developing diabetes. People with prediabetes have impaired fasting glucose (100‐125 mg/dL), impaired glucose tolerance (140‐199 mg/dL at 2 hours), or both.16 The actual national burden of diabetes most likely exceeds the $174 billion estimate because of excess medical costs associated with prediabetic patients.

Due to the impracticality of the 2 tests mentioned above as screening methods for diabetes and prediabetes, we used HbA1c to screen for glucose metabolism disturbance. This marker does not need overnight fasting or a 2‐hour glucose loading test. The HbA1c level gives an average of glycemic control over the previous 120 days, as red blood cells have a lifespan of 120 days. Although the use of HbA1c for the diagnosis of diabetes is not yet established, its availability at the time when the patient is seen (point‐of‐care testing) is a great advantage over fasting glucose and glucose tolerance tests.17, 18 The normal range for a person without diabetes is 4.3% to 5.9%.19 For most people with diabetes the American Diabetes Association recommends targeting an HbA1c of 7% or less. If HbA1c is 8% or higher, it means that the patient's blood glucose is not well‐controlled and he/she is at increased risk for developing diabetic complications. In this case, the patient needs modifications in his/her diet, physical activity, oral hypoglycemic medications, or insulin. It is uncommon to have patients with a history of diabetes and HbA1c < 6.1%. Our patient sample confirms this fact (n = 14). Therefore, it was not included in the statistical analysis.

The cutpoint 6.1% (2 SD above the mean) was the recommended cutoff point for HbA1c in most reviewed studies.15, 20 At the Diabetes Control and Complications Trial and Prospective Diabetes Study, the sensitivity of this cutpoint in detecting diabetes was 78% to 81% and specificity was 79% to 84%.15 HbA1c was shown to have less intraindividual variation and better predicts both microvascular and macrovascular complications.15 Although the current cost of HbA1c is higher than fasting plasma glucose, its feasibility as a screening tool for DM and as a predictor of its costly preventable complications may make it a cost‐effective choice.

Unrecognized glycometabolic disturbance as measured by HbA1c have recently been associated with poor outcomes, for example, after acute myocardial infarction.21 Postoperative complications in diabetic patients have been attributed to impairments in the immune system and microangiopathy. Patients with poorly regulated glucose levels are at an increased risk for developing infections. Once a person with diabetes has developed an infection, the body is less capable of fighting it off because high glucose levels interfere with the normal function of white blood cells. Moreover, dysfunction in the immune system impairs the inflammatory reaction in local tissues, which is further aggravated by the reduced blood supply due to diabetic microangiopathy. This results in considerable increase in the risk of soft‐tissue complications and significant delays in wound and bone healing.22

Our patient sample was classified according to chart and laboratory findings. The two criteria we used to classify them were a history of diabetes and HbA1c level 6.1%. Results show that patients unaware about their elevated HbA1c level are almost equal to the percentage of patients with history of diabetes. Combined, they make slightly more than 25% of spine surgery patients. These results are consistent with the CDC's estimate of the percentage of diabetes and prediabetes in the general population.3 Further analysis shows that age and BMI are significantly different between DM‐HbA1c groups, which is unsurprising since the correlation of diabetes with age and BMI is well‐established.23 Interestingly, the subclinical patients with elevated HbA1c appear to be as old as nondiabetic patients but as heavy as their diabetic peers. This is a remarkable finding that reflects the transitional status of these patients between non‐diabetes and diabetes. In addition, age and BMI were found to be very significant determinants of total cost in spine surgery patients. Actually, they were the reasons behind the statistical significance shown by the DM‐HbA1c status regarding cost as exposed by the ANCOVA.

This middle category of spine surgery patients with subclinical glucose metabolism disturbance seems to have important economic implications in terms of LOS and total cost in the LDF group. This may be due to the larger share of this middle subgroup in the LDF group of patients, as shown above. Besides, LDF patients stay longer and cost more than other spine surgery patients and consequently statistical differences between DM‐HbA1c subgroups are more evident. LDF is major surgery, with extensive dissection, greater blood loss, and longer operative time than other types of spine surgery and the patients are older and sicker. That may be why there was a more pronounced difference in LOS and cost between its 3 subgroups.

Overall, this work expands upon our understanding of the importance of diabetes and undiagnosed elevation of HbA1c in affecting cost following surgery. However, the study has several limitations that should be taken into consideration. Potential underreporting of diabetes in the patient's chart could skew the results, although this was unlikely due to the repetitive interview of patients on multiple occasions. In addition, HbA1c level could be affected by prescribed medications, which were not included in our inquiries. LOS and cost could also be influenced by non‐diabetes‐related factors that were not considered in the study. Finally, a bigger sample would have given more power to the results, although 556 patients is, without a doubt, not a small group.

Conclusions

There is a significant segment of spine surgery patients who learn of their disturbed glucose metabolism status for the first time on their preoperative visit. These patients require further investigation, with a fasting glucose test to confirm their diabetes status, and they need to start treatment early to prevent future complications.

HbA1c testing should be considered in the routine preoperative workup of spine surgery patients. This is a simple point‐of‐care test and its results can be obtained without delay. This will help improve early diagnosis of prediabetes and diabetes and may prevent the onset of type 2 diabetes, thus improving the patient's health and final outcome.

We need continuing research into the healthcare costs of diabetic patients in different medical specialties, as this will improve awareness about the economic impact and cost‐effectiveness issues related to this prevalent disease.

Pulmonary embolism (PE) and deep vein thrombosis (DVT), collectively referred to as venous thromboembolism (VTE), represent a major public health problem, affecting hundreds of thousands of Americans each year.1 The best estimates are that at least 100,000 deaths are attributable to VTE each year in the United States alone.1 VTE is primarily a problem of hospitalized and recently‐hospitalized patients.2 Although a recent meta‐analysis did not prove mortality benefit of prophylaxis in the medical population,3 PE is frequently estimated to be the most common preventable cause of hospital death.46

Pharmacologic methods to prevent VTE are safe, effective, cost‐effective, and advocated by authoritative guidelines.7 Even though the majority of medical and surgical inpatients have multiple risk factors for VTE, large prospective studies continue to demonstrate that these preventive methods are significantly underutilized, often with only 30% to 50% eligible patients receiving prophylaxis.812

The reasons for this underutilization include lack of physician familiarity or agreement with guidelines, underestimation of VTE risk, concern over risk of bleeding, and the perception that the guidelines are resource‐intensive or difficult to implement in a practical fashion.13 While many VTE risk‐assessment models are available in the literature,1418 a lack of prospectively validated models and issues regarding ease of use have further hampered widespread integration of VTE risk assessments into order sets and inpatient practice.

We sought to optimize prevention of hospital‐acquired (HA) VTE in our 350‐bed tertiary‐care academic center using a VTE prevention protocol and a multifaceted approach that could be replicated across a wide variety of medical centers.

Patients and Methods

Results

There were 30,850 adult medical/surgical inpatients admitted to the medical center with a length of stay of 48 hours or more in 2005 to 2007, representing 186,397 patient‐days of observation. A total of 2,924 of these patients were randomly sampled during the VTE prophylaxis audit process (mean 81 audits per month). Table 2 shows the characteristics of randomly sampled audit patients and of the patients diagnosed with HA VTE. The demographics of the 30,850‐inpatient population (mean age = 50 years; 60.7% male; 52% Surgical Services) mirrored the demographics of the randomly sampled inpatients that underwent audits, validating the random sampling methods.

The majority of inpatients sampled in the audits were in the moderate VTE risk category (84%), 12% were in the high‐risk category, and 4% were in the low‐risk category. The distribution of VTE risk did not change significantly over this time period.

Impact on Percent of Patients with Adequate Prophylaxis (Longitudinal Audits)

Audits of randomly sampled inpatients occurred longitudinally throughout the study period as described above. Based on the intervention, the percent of patients on adequate prophylaxis improved significantly (P < 0.001) by each calendar year (see Table 3), from a baseline of 58% in 2005 to 78% in 2006 (unadjusted relative benefit = 1.35; 95% confidence interval [CI] = 1.28‐1.43), and 93% in 2007 (unadjusted relative benefit = 1.61; 95% CI = 1.52, 1.69). The improvement seen was more marked in the moderate VTE risk patients when compared to the high VTE risk patients. The percent of audited VTE prophylaxis improved from 53% in calendar year (CY) 2005 to 93% in 2007 (unadjusted relative benefit = 1.75; 95% CI = 1.70‐1.81) in the moderate VTE risk group, while the high VTE risk group improved from 83% to 92% in the same time period (unadjusted relative benefit = 1.11; 95% CI = 0.95‐1.25).

Table 3.Unadjusted Risk Ratio (Relative Benefit) of Receiving Adequate Venous Thromboembolism Prophylaxis by Year, in Randomly Selected Inpatients

	2005	2006	2007
Abbreviation: CI, confidence interval. * P < 0.001.
All audits	1279	960	679
Prophylaxis adequate, n (%)	740 (58)	751 (78)	631 (93)
Relative benefit (95% CI)	1	1.35* (1.28‐1.43)	1.61* (1.52‐1.69)

Overall, adequate VTE prophylaxis was present in over 98% of audited patients in the last 6 months of 2007, and this high rate has been sustained throughout 2008. Age, ethnicity, and gender were not associated with differential rates of adequate VTE prophylaxis.

Figure 1 is a timeline of interventions and the impact on the prevalence of adequate VTE prophylaxis. The first 7 to 8 months represent the baseline rate 50% to 55% of VTE prophylaxis. In this baseline period, the improvement team was meeting, but had not yet begun meeting with the large variety of medical and surgical service leaders. Consensus‐building sessions with these leaders in the latter part of 2005 through mid‐2006 correlated with improvement in adequate VTE prophylaxis rates to near 70%. The consensus‐building sessions also prepared these varied services for a go live date of the modular order set that was incorporated into all admit and transfer order sets, often replacing preexisting orders referring to VTE prevention measures. The order set resulted in an improvement to 80% adequate prophylaxis, with the incremental improvement occurring virtually overnight with the go live date at the onset of quarter 2 (Q2) of 2006. Monitoring of the order set use confirmed that it was easy and efficient to use, but also revealed that physicians were at times classifying patients as low VTE risk inaccurately, when they possessed qualities that actually qualified them for moderate risk status by our protocol. We therefore inserted a secondary CPOE screen when patients were categorized as low VTE risk, asking the physician to deny or confirm that the patient had no risk factors that qualified them for moderate risk status. This confirmation screen essentially acted as a reminder to the physician to ask Are you sure this patient does not need VTE prophylaxis? This minor modification of the CPOE order set improved adequate VTE prophylaxis rates to 90%. Finally, we asked nurses to evaluate patients who were not on therapeutic or prophylactic doses of anticoagulants. Patients with VTE risk factors but no obvious contraindications generated a note from the nurse to the doctor, prompting the doctor to reassess VTE risk and potential contraindications. This simple intervention raised the percent of audited patients on adequate VTE prophylaxis to 98% in the last 6 months of 2007.

Figure 1

Discussion

We demonstrated that implementation of a standardized VTE prevention protocol and order set could result in a dramatic and sustained increase in adequate VTE prophylaxis across an entire adult inpatient population. This achievement is more remarkable given the rigorous criteria defining adequate prophylaxis. Mechanical compression devices were not accepted as primary prophylaxis in moderate‐risk or high‐risk patients unless there was a documented contraindication to pharmacologic prophylaxis, and high VTE risk patients required both mechanical and pharmacologic prophylaxis to be considered adequately protected, for example. The relegation of mechanical prophylaxis to an ancillary role was endorsed by our direct observations, in that we were only able to verify that ordered mechanical prophylaxis was in place 60% of the time.

The passive dissemination of guidelines is ineffective in securing VTE prophylaxis.19 Improvement in VTE prophylaxis has been suboptimal when options for VTE prophylaxis are offered without providing guidance for VTE risk stratification and all options (pharmacologic, mechanical, or no prophylaxis) are presented as equally acceptable choices.20, 21 Our multifaceted strategy using multiple interventions is an approach endorsed by a recent systematic review19 and others in the literature.22, 23 The interventions we enacted included a method to prompt clinicians to assess patients for VTE risk, and then to assist in the selection of appropriate prophylaxis from standardized options. Decision support and clinical reminders have been shown to be more effective when integrated into the workflow19, 24; therefore, a key strategy of our study involved embedding the VTE risk assessment tool and guidance toward appropriate prophylactic regimens into commonly used admission/transfer order sets. We addressed the barriers of physician unfamiliarity or disagreement with guidelines10 with education and consensus‐building sessions with clinical leadership. Clinical feedback from audits, peer review, and nursing‐led interventions rounded out the layered multifaceted interventional approach.

We designed and prospectively validated a VTE RAM during the course of our improvement efforts, and to our knowledge our simple 3‐category (or 3‐level) VTE risk assessment model is the only validated model. The VTE risk assessment/prevention protocol was validated by several important parameters. First, it proved to be practical and easy to use, taking only seconds to complete, and it was readily adopted by all adult medical and surgical services. Second, the VTE RAM demonstrated excellent interobserver agreement for VTE risk level and decisions about adequacy of VTE prophylaxis with 5 physician reviewers. Third, the VTE RAM predicted risk for VTE. All patients suffering from HA VTE were in the moderate‐risk to high‐risk categories, and HA VTE occurred disproportionately in those meeting criteria for high risk. Fourth, implementation of the VTE RAM/protocol resulted in very high, sustained levels of VTE prophylaxis without any detectable safety concerns. Finally and perhaps most importantly, high rates of adherence to the VTE protocol resulted in a 40% decline in the incidence of HA VTE in our institution.

The improved prevalence of adequate VTE prophylaxis reduced, but did not eliminate, HA VTE. The reduction observed is consistent with the 40% to 50% efficacy of prophylaxis reported in the literature.7 Our experience highlights the recent controversy over proposals by the Centers for Medicare & Medicaid Services (CMS) to add HA VTE to the list of do not pay conditions later this year,25 as it is clear from our data that even near‐perfect adherence with accepted VTE prevention measures will not eliminate HA VTE. After vigorous pushback about the fairness of this measure, the HA VTE do not pay scope was narrowed to include only certain major orthopedic procedure patients.

Services with a preponderance of moderate‐risk patients had the largest reduction in HA VTE. Efforts that are focused only on high‐risk orthopedic, trauma, and critical care patients will miss the larger opportunities for maximal reduction in HA VTE for multiple reasons. First, moderate VTE risk patients are far more prevalent than high VTE risk patients (84% vs. 12% of inpatients at our institution). Second, high‐risk patients are already at a baseline relatively high rate of VTE prophylaxis compared to their moderate VTE risk counterparts (83% vs. 53% at our institution). Third, a large portion of patients at high risk for VTE (such as trauma patients) also have the largest prevalence of absolute or relative contraindications to pharmacologic prophylaxis, limiting the effect size of prevention efforts.

Major strengths of this study included ongoing rigorous concurrent measurement of both processes (percent of patients on adequate prophylaxis) and outcomes (HA VTE diagnosed via imaging studies) over a prolonged time period. The robust random sampling of inpatients insured that changes in VTE prophylaxis rates were not due to changes in the distribution of VTE risk or bias potentially introduced from convenience samples. The longitudinal monitoring of imaging study results for VTE cases is vastly superior to using administrative data that is reliant on coding. The recent University Healthsystem Consortium (UHC) benchmarking data on venous thromboembolism were sobering but instructive.26 UHC used administrative discharge codes for VTE in a secondary position to identify patients with HA VTE, which is a common strategy to follow the incidence of HA VTE. The accuracy of identifying surgical patients with an HA VTE was only 60%. Proper use of the present on admission (POA) designation would have improved this to 83%, but 17% of cases either did not occur or had history only with a labor‐intensive manual chart review. Performance was even worse in medical patients, with only a 30% accuracy rate, potentially improved to 79% if accurate POA designation had been used, and 21% of cases identified by administrative methods either did not occur or had history only. In essence, unless an improvement team uses chart review of each case potentially identified as a HA VTE case, the administrative data are not reliable. Concurrent discovery of VTE cases allows for a more accurate and timely chart review, and allows for near real‐time feedback to the responsible treatment team.

The major limitation of this study is inherent in the observational design and the lack of a control population. Other factors besides our VTE‐specific improvement efforts could affect process and outcomes, and reductions in HA VTE could conceivably occur because of changes in the make‐up of the admitted inpatient population. These limitations are mitigated to some degree by several observations. The VTE risk distribution in the randomly sampled inpatient population did not vary significantly from year to year. The number of HA VTE was reduced in 2007 even though the number of patients and patient days at risk for developing VTE went up. The incidence of community‐acquired VTE remained constant over the same time period, highlighting the consistency of our measurement techniques and the VTE risk in the community we serve. Last, the improvements in VTE prophylaxis rates increased at times that correlated well with the introduction of layered interventions, as depicted in Figure 1.

There were several limitations to the internal study on adverse effects of VTE protocol implementation. First, this was a retrospective study, so much of the data collection was dependent upon physician progress notes and discharge summaries. Lack of documentation could have precluded the appropriate diagnosis codes from being assigned. Next, the study population was generated from coding data, so subjectivity could have been introduced during the coding process. Also, a majority of the patients did not fit the study criteria due to discharge with the e934.2 code, because they were found to have an elevated international normalized ratio (INR) after being admitted on warfarin. Finally, chart‐reviewer bias could have affected the results, as the chart reviewer became more proficient at reviewing charts over time. Despite these limitations, the study methodology allowed for screening of a large population for rare events. Bleeding may be a frequent concern with primary thromboprophylaxis, but data from clinical trials and this study help to demonstrate that rates of adverse events from pharmacologic VTE prophylaxis are very rare.

Another potential limitation is raised by the question of whether our methods can be generalized to other sites. Our site is an academic medical center and we have CPOE, which is present in only a small minority of centers. Furthermore, one could question how feasible it is to get institution‐wide consensus for a VTE prevention protocol in settings with heterogenous medical staffs. To address these issues, we used a proven performance improvement framework calling for administrative support, a multidisciplinary improvement team, reliable measures, and a multifaceted approach to interventions. This framework and our experiences have been incorporated into improvement guides27, 28 that have been the centerpiece of the Society of Hospital Medicine VTE Prevention Collaborative improvement efforts in a wide variety of medical environments. The collaborative leadership has observed that success is the rule when this model is followed, in institutions large and small, academic or community, and in both paper and CPOE environments. Not all of these sites use a VTE RAM identical to ours, and there are local nuances to preferred choices of prophylaxis. However, they all incorporated simple VTE risk stratification with only a few levels of risk. Reinforcing the expectation that pharmacologic prophylaxis is indicated for the majority of inpatients is likely more important than the nuances of choices for each risk level.

We demonstrated that dramatic improvement in VTE prophylaxis is achievable, safe, and effective in reducing the incidence of HA VTE. We used scalable, portable methods to make a large and convincing impact on the incidence of HA VTE, while also developing and prospectively validating a VTE RAM. A wide variety of institutions are achieving significant improvement using similar strategies. Future research and improvement efforts should focus on how to accelerate integration of this model across networks of hospitals, leveraging networks with common order sets or information systems. Widespread success in improving VTE prophylaxis would likely have a far‐reaching benefit on morbidity and PE‐related mortality.

Pulmonary embolism (PE) and deep vein thrombosis (DVT), collectively referred to as venous thromboembolism (VTE), represent a major public health problem, affecting hundreds of thousands of Americans each year.1 The best estimates are that at least 100,000 deaths are attributable to VTE each year in the United States alone.1 VTE is primarily a problem of hospitalized and recently‐hospitalized patients.2 Although a recent meta‐analysis did not prove mortality benefit of prophylaxis in the medical population,3 PE is frequently estimated to be the most common preventable cause of hospital death.46

Pharmacologic methods to prevent VTE are safe, effective, cost‐effective, and advocated by authoritative guidelines.7 Even though the majority of medical and surgical inpatients have multiple risk factors for VTE, large prospective studies continue to demonstrate that these preventive methods are significantly underutilized, often with only 30% to 50% eligible patients receiving prophylaxis.812

The reasons for this underutilization include lack of physician familiarity or agreement with guidelines, underestimation of VTE risk, concern over risk of bleeding, and the perception that the guidelines are resource‐intensive or difficult to implement in a practical fashion.13 While many VTE risk‐assessment models are available in the literature,1418 a lack of prospectively validated models and issues regarding ease of use have further hampered widespread integration of VTE risk assessments into order sets and inpatient practice.

We sought to optimize prevention of hospital‐acquired (HA) VTE in our 350‐bed tertiary‐care academic center using a VTE prevention protocol and a multifaceted approach that could be replicated across a wide variety of medical centers.

Patients and Methods

Results

There were 30,850 adult medical/surgical inpatients admitted to the medical center with a length of stay of 48 hours or more in 2005 to 2007, representing 186,397 patient‐days of observation. A total of 2,924 of these patients were randomly sampled during the VTE prophylaxis audit process (mean 81 audits per month). Table 2 shows the characteristics of randomly sampled audit patients and of the patients diagnosed with HA VTE. The demographics of the 30,850‐inpatient population (mean age = 50 years; 60.7% male; 52% Surgical Services) mirrored the demographics of the randomly sampled inpatients that underwent audits, validating the random sampling methods.

The majority of inpatients sampled in the audits were in the moderate VTE risk category (84%), 12% were in the high‐risk category, and 4% were in the low‐risk category. The distribution of VTE risk did not change significantly over this time period.

Impact on Percent of Patients with Adequate Prophylaxis (Longitudinal Audits)

Audits of randomly sampled inpatients occurred longitudinally throughout the study period as described above. Based on the intervention, the percent of patients on adequate prophylaxis improved significantly (P < 0.001) by each calendar year (see Table 3), from a baseline of 58% in 2005 to 78% in 2006 (unadjusted relative benefit = 1.35; 95% confidence interval [CI] = 1.28‐1.43), and 93% in 2007 (unadjusted relative benefit = 1.61; 95% CI = 1.52, 1.69). The improvement seen was more marked in the moderate VTE risk patients when compared to the high VTE risk patients. The percent of audited VTE prophylaxis improved from 53% in calendar year (CY) 2005 to 93% in 2007 (unadjusted relative benefit = 1.75; 95% CI = 1.70‐1.81) in the moderate VTE risk group, while the high VTE risk group improved from 83% to 92% in the same time period (unadjusted relative benefit = 1.11; 95% CI = 0.95‐1.25).

Table 3.Unadjusted Risk Ratio (Relative Benefit) of Receiving Adequate Venous Thromboembolism Prophylaxis by Year, in Randomly Selected Inpatients

	2005	2006	2007
Abbreviation: CI, confidence interval. * P < 0.001.
All audits	1279	960	679
Prophylaxis adequate, n (%)	740 (58)	751 (78)	631 (93)
Relative benefit (95% CI)	1	1.35* (1.28‐1.43)	1.61* (1.52‐1.69)

Overall, adequate VTE prophylaxis was present in over 98% of audited patients in the last 6 months of 2007, and this high rate has been sustained throughout 2008. Age, ethnicity, and gender were not associated with differential rates of adequate VTE prophylaxis.

Figure 1 is a timeline of interventions and the impact on the prevalence of adequate VTE prophylaxis. The first 7 to 8 months represent the baseline rate 50% to 55% of VTE prophylaxis. In this baseline period, the improvement team was meeting, but had not yet begun meeting with the large variety of medical and surgical service leaders. Consensus‐building sessions with these leaders in the latter part of 2005 through mid‐2006 correlated with improvement in adequate VTE prophylaxis rates to near 70%. The consensus‐building sessions also prepared these varied services for a go live date of the modular order set that was incorporated into all admit and transfer order sets, often replacing preexisting orders referring to VTE prevention measures. The order set resulted in an improvement to 80% adequate prophylaxis, with the incremental improvement occurring virtually overnight with the go live date at the onset of quarter 2 (Q2) of 2006. Monitoring of the order set use confirmed that it was easy and efficient to use, but also revealed that physicians were at times classifying patients as low VTE risk inaccurately, when they possessed qualities that actually qualified them for moderate risk status by our protocol. We therefore inserted a secondary CPOE screen when patients were categorized as low VTE risk, asking the physician to deny or confirm that the patient had no risk factors that qualified them for moderate risk status. This confirmation screen essentially acted as a reminder to the physician to ask Are you sure this patient does not need VTE prophylaxis? This minor modification of the CPOE order set improved adequate VTE prophylaxis rates to 90%. Finally, we asked nurses to evaluate patients who were not on therapeutic or prophylactic doses of anticoagulants. Patients with VTE risk factors but no obvious contraindications generated a note from the nurse to the doctor, prompting the doctor to reassess VTE risk and potential contraindications. This simple intervention raised the percent of audited patients on adequate VTE prophylaxis to 98% in the last 6 months of 2007.

Figure 1

Discussion

We demonstrated that implementation of a standardized VTE prevention protocol and order set could result in a dramatic and sustained increase in adequate VTE prophylaxis across an entire adult inpatient population. This achievement is more remarkable given the rigorous criteria defining adequate prophylaxis. Mechanical compression devices were not accepted as primary prophylaxis in moderate‐risk or high‐risk patients unless there was a documented contraindication to pharmacologic prophylaxis, and high VTE risk patients required both mechanical and pharmacologic prophylaxis to be considered adequately protected, for example. The relegation of mechanical prophylaxis to an ancillary role was endorsed by our direct observations, in that we were only able to verify that ordered mechanical prophylaxis was in place 60% of the time.

The passive dissemination of guidelines is ineffective in securing VTE prophylaxis.19 Improvement in VTE prophylaxis has been suboptimal when options for VTE prophylaxis are offered without providing guidance for VTE risk stratification and all options (pharmacologic, mechanical, or no prophylaxis) are presented as equally acceptable choices.20, 21 Our multifaceted strategy using multiple interventions is an approach endorsed by a recent systematic review19 and others in the literature.22, 23 The interventions we enacted included a method to prompt clinicians to assess patients for VTE risk, and then to assist in the selection of appropriate prophylaxis from standardized options. Decision support and clinical reminders have been shown to be more effective when integrated into the workflow19, 24; therefore, a key strategy of our study involved embedding the VTE risk assessment tool and guidance toward appropriate prophylactic regimens into commonly used admission/transfer order sets. We addressed the barriers of physician unfamiliarity or disagreement with guidelines10 with education and consensus‐building sessions with clinical leadership. Clinical feedback from audits, peer review, and nursing‐led interventions rounded out the layered multifaceted interventional approach.

We designed and prospectively validated a VTE RAM during the course of our improvement efforts, and to our knowledge our simple 3‐category (or 3‐level) VTE risk assessment model is the only validated model. The VTE risk assessment/prevention protocol was validated by several important parameters. First, it proved to be practical and easy to use, taking only seconds to complete, and it was readily adopted by all adult medical and surgical services. Second, the VTE RAM demonstrated excellent interobserver agreement for VTE risk level and decisions about adequacy of VTE prophylaxis with 5 physician reviewers. Third, the VTE RAM predicted risk for VTE. All patients suffering from HA VTE were in the moderate‐risk to high‐risk categories, and HA VTE occurred disproportionately in those meeting criteria for high risk. Fourth, implementation of the VTE RAM/protocol resulted in very high, sustained levels of VTE prophylaxis without any detectable safety concerns. Finally and perhaps most importantly, high rates of adherence to the VTE protocol resulted in a 40% decline in the incidence of HA VTE in our institution.

The improved prevalence of adequate VTE prophylaxis reduced, but did not eliminate, HA VTE. The reduction observed is consistent with the 40% to 50% efficacy of prophylaxis reported in the literature.7 Our experience highlights the recent controversy over proposals by the Centers for Medicare & Medicaid Services (CMS) to add HA VTE to the list of do not pay conditions later this year,25 as it is clear from our data that even near‐perfect adherence with accepted VTE prevention measures will not eliminate HA VTE. After vigorous pushback about the fairness of this measure, the HA VTE do not pay scope was narrowed to include only certain major orthopedic procedure patients.

Services with a preponderance of moderate‐risk patients had the largest reduction in HA VTE. Efforts that are focused only on high‐risk orthopedic, trauma, and critical care patients will miss the larger opportunities for maximal reduction in HA VTE for multiple reasons. First, moderate VTE risk patients are far more prevalent than high VTE risk patients (84% vs. 12% of inpatients at our institution). Second, high‐risk patients are already at a baseline relatively high rate of VTE prophylaxis compared to their moderate VTE risk counterparts (83% vs. 53% at our institution). Third, a large portion of patients at high risk for VTE (such as trauma patients) also have the largest prevalence of absolute or relative contraindications to pharmacologic prophylaxis, limiting the effect size of prevention efforts.

Major strengths of this study included ongoing rigorous concurrent measurement of both processes (percent of patients on adequate prophylaxis) and outcomes (HA VTE diagnosed via imaging studies) over a prolonged time period. The robust random sampling of inpatients insured that changes in VTE prophylaxis rates were not due to changes in the distribution of VTE risk or bias potentially introduced from convenience samples. The longitudinal monitoring of imaging study results for VTE cases is vastly superior to using administrative data that is reliant on coding. The recent University Healthsystem Consortium (UHC) benchmarking data on venous thromboembolism were sobering but instructive.26 UHC used administrative discharge codes for VTE in a secondary position to identify patients with HA VTE, which is a common strategy to follow the incidence of HA VTE. The accuracy of identifying surgical patients with an HA VTE was only 60%. Proper use of the present on admission (POA) designation would have improved this to 83%, but 17% of cases either did not occur or had history only with a labor‐intensive manual chart review. Performance was even worse in medical patients, with only a 30% accuracy rate, potentially improved to 79% if accurate POA designation had been used, and 21% of cases identified by administrative methods either did not occur or had history only. In essence, unless an improvement team uses chart review of each case potentially identified as a HA VTE case, the administrative data are not reliable. Concurrent discovery of VTE cases allows for a more accurate and timely chart review, and allows for near real‐time feedback to the responsible treatment team.

The major limitation of this study is inherent in the observational design and the lack of a control population. Other factors besides our VTE‐specific improvement efforts could affect process and outcomes, and reductions in HA VTE could conceivably occur because of changes in the make‐up of the admitted inpatient population. These limitations are mitigated to some degree by several observations. The VTE risk distribution in the randomly sampled inpatient population did not vary significantly from year to year. The number of HA VTE was reduced in 2007 even though the number of patients and patient days at risk for developing VTE went up. The incidence of community‐acquired VTE remained constant over the same time period, highlighting the consistency of our measurement techniques and the VTE risk in the community we serve. Last, the improvements in VTE prophylaxis rates increased at times that correlated well with the introduction of layered interventions, as depicted in Figure 1.

There were several limitations to the internal study on adverse effects of VTE protocol implementation. First, this was a retrospective study, so much of the data collection was dependent upon physician progress notes and discharge summaries. Lack of documentation could have precluded the appropriate diagnosis codes from being assigned. Next, the study population was generated from coding data, so subjectivity could have been introduced during the coding process. Also, a majority of the patients did not fit the study criteria due to discharge with the e934.2 code, because they were found to have an elevated international normalized ratio (INR) after being admitted on warfarin. Finally, chart‐reviewer bias could have affected the results, as the chart reviewer became more proficient at reviewing charts over time. Despite these limitations, the study methodology allowed for screening of a large population for rare events. Bleeding may be a frequent concern with primary thromboprophylaxis, but data from clinical trials and this study help to demonstrate that rates of adverse events from pharmacologic VTE prophylaxis are very rare.

Another potential limitation is raised by the question of whether our methods can be generalized to other sites. Our site is an academic medical center and we have CPOE, which is present in only a small minority of centers. Furthermore, one could question how feasible it is to get institution‐wide consensus for a VTE prevention protocol in settings with heterogenous medical staffs. To address these issues, we used a proven performance improvement framework calling for administrative support, a multidisciplinary improvement team, reliable measures, and a multifaceted approach to interventions. This framework and our experiences have been incorporated into improvement guides27, 28 that have been the centerpiece of the Society of Hospital Medicine VTE Prevention Collaborative improvement efforts in a wide variety of medical environments. The collaborative leadership has observed that success is the rule when this model is followed, in institutions large and small, academic or community, and in both paper and CPOE environments. Not all of these sites use a VTE RAM identical to ours, and there are local nuances to preferred choices of prophylaxis. However, they all incorporated simple VTE risk stratification with only a few levels of risk. Reinforcing the expectation that pharmacologic prophylaxis is indicated for the majority of inpatients is likely more important than the nuances of choices for each risk level.

We demonstrated that dramatic improvement in VTE prophylaxis is achievable, safe, and effective in reducing the incidence of HA VTE. We used scalable, portable methods to make a large and convincing impact on the incidence of HA VTE, while also developing and prospectively validating a VTE RAM. A wide variety of institutions are achieving significant improvement using similar strategies. Future research and improvement efforts should focus on how to accelerate integration of this model across networks of hospitals, leveraging networks with common order sets or information systems. Widespread success in improving VTE prophylaxis would likely have a far‐reaching benefit on morbidity and PE‐related mortality.

Pulmonary embolism (PE) and deep vein thrombosis (DVT), collectively referred to as venous thromboembolism (VTE), represent a major public health problem, affecting hundreds of thousands of Americans each year.1 The best estimates are that at least 100,000 deaths are attributable to VTE each year in the United States alone.1 VTE is primarily a problem of hospitalized and recently‐hospitalized patients.2 Although a recent meta‐analysis did not prove mortality benefit of prophylaxis in the medical population,3 PE is frequently estimated to be the most common preventable cause of hospital death.46

Pharmacologic methods to prevent VTE are safe, effective, cost‐effective, and advocated by authoritative guidelines.7 Even though the majority of medical and surgical inpatients have multiple risk factors for VTE, large prospective studies continue to demonstrate that these preventive methods are significantly underutilized, often with only 30% to 50% eligible patients receiving prophylaxis.812

The reasons for this underutilization include lack of physician familiarity or agreement with guidelines, underestimation of VTE risk, concern over risk of bleeding, and the perception that the guidelines are resource‐intensive or difficult to implement in a practical fashion.13 While many VTE risk‐assessment models are available in the literature,1418 a lack of prospectively validated models and issues regarding ease of use have further hampered widespread integration of VTE risk assessments into order sets and inpatient practice.

We sought to optimize prevention of hospital‐acquired (HA) VTE in our 350‐bed tertiary‐care academic center using a VTE prevention protocol and a multifaceted approach that could be replicated across a wide variety of medical centers.

Patients and Methods

Results

There were 30,850 adult medical/surgical inpatients admitted to the medical center with a length of stay of 48 hours or more in 2005 to 2007, representing 186,397 patient‐days of observation. A total of 2,924 of these patients were randomly sampled during the VTE prophylaxis audit process (mean 81 audits per month). Table 2 shows the characteristics of randomly sampled audit patients and of the patients diagnosed with HA VTE. The demographics of the 30,850‐inpatient population (mean age = 50 years; 60.7% male; 52% Surgical Services) mirrored the demographics of the randomly sampled inpatients that underwent audits, validating the random sampling methods.

The majority of inpatients sampled in the audits were in the moderate VTE risk category (84%), 12% were in the high‐risk category, and 4% were in the low‐risk category. The distribution of VTE risk did not change significantly over this time period.

Impact on Percent of Patients with Adequate Prophylaxis (Longitudinal Audits)

Audits of randomly sampled inpatients occurred longitudinally throughout the study period as described above. Based on the intervention, the percent of patients on adequate prophylaxis improved significantly (P < 0.001) by each calendar year (see Table 3), from a baseline of 58% in 2005 to 78% in 2006 (unadjusted relative benefit = 1.35; 95% confidence interval [CI] = 1.28‐1.43), and 93% in 2007 (unadjusted relative benefit = 1.61; 95% CI = 1.52, 1.69). The improvement seen was more marked in the moderate VTE risk patients when compared to the high VTE risk patients. The percent of audited VTE prophylaxis improved from 53% in calendar year (CY) 2005 to 93% in 2007 (unadjusted relative benefit = 1.75; 95% CI = 1.70‐1.81) in the moderate VTE risk group, while the high VTE risk group improved from 83% to 92% in the same time period (unadjusted relative benefit = 1.11; 95% CI = 0.95‐1.25).

Table 3.Unadjusted Risk Ratio (Relative Benefit) of Receiving Adequate Venous Thromboembolism Prophylaxis by Year, in Randomly Selected Inpatients

	2005	2006	2007
Abbreviation: CI, confidence interval. * P < 0.001.
All audits	1279	960	679
Prophylaxis adequate, n (%)	740 (58)	751 (78)	631 (93)
Relative benefit (95% CI)	1	1.35* (1.28‐1.43)	1.61* (1.52‐1.69)

Overall, adequate VTE prophylaxis was present in over 98% of audited patients in the last 6 months of 2007, and this high rate has been sustained throughout 2008. Age, ethnicity, and gender were not associated with differential rates of adequate VTE prophylaxis.

Figure 1 is a timeline of interventions and the impact on the prevalence of adequate VTE prophylaxis. The first 7 to 8 months represent the baseline rate 50% to 55% of VTE prophylaxis. In this baseline period, the improvement team was meeting, but had not yet begun meeting with the large variety of medical and surgical service leaders. Consensus‐building sessions with these leaders in the latter part of 2005 through mid‐2006 correlated with improvement in adequate VTE prophylaxis rates to near 70%. The consensus‐building sessions also prepared these varied services for a go live date of the modular order set that was incorporated into all admit and transfer order sets, often replacing preexisting orders referring to VTE prevention measures. The order set resulted in an improvement to 80% adequate prophylaxis, with the incremental improvement occurring virtually overnight with the go live date at the onset of quarter 2 (Q2) of 2006. Monitoring of the order set use confirmed that it was easy and efficient to use, but also revealed that physicians were at times classifying patients as low VTE risk inaccurately, when they possessed qualities that actually qualified them for moderate risk status by our protocol. We therefore inserted a secondary CPOE screen when patients were categorized as low VTE risk, asking the physician to deny or confirm that the patient had no risk factors that qualified them for moderate risk status. This confirmation screen essentially acted as a reminder to the physician to ask Are you sure this patient does not need VTE prophylaxis? This minor modification of the CPOE order set improved adequate VTE prophylaxis rates to 90%. Finally, we asked nurses to evaluate patients who were not on therapeutic or prophylactic doses of anticoagulants. Patients with VTE risk factors but no obvious contraindications generated a note from the nurse to the doctor, prompting the doctor to reassess VTE risk and potential contraindications. This simple intervention raised the percent of audited patients on adequate VTE prophylaxis to 98% in the last 6 months of 2007.

Figure 1

Discussion

We demonstrated that implementation of a standardized VTE prevention protocol and order set could result in a dramatic and sustained increase in adequate VTE prophylaxis across an entire adult inpatient population. This achievement is more remarkable given the rigorous criteria defining adequate prophylaxis. Mechanical compression devices were not accepted as primary prophylaxis in moderate‐risk or high‐risk patients unless there was a documented contraindication to pharmacologic prophylaxis, and high VTE risk patients required both mechanical and pharmacologic prophylaxis to be considered adequately protected, for example. The relegation of mechanical prophylaxis to an ancillary role was endorsed by our direct observations, in that we were only able to verify that ordered mechanical prophylaxis was in place 60% of the time.

The passive dissemination of guidelines is ineffective in securing VTE prophylaxis.19 Improvement in VTE prophylaxis has been suboptimal when options for VTE prophylaxis are offered without providing guidance for VTE risk stratification and all options (pharmacologic, mechanical, or no prophylaxis) are presented as equally acceptable choices.20, 21 Our multifaceted strategy using multiple interventions is an approach endorsed by a recent systematic review19 and others in the literature.22, 23 The interventions we enacted included a method to prompt clinicians to assess patients for VTE risk, and then to assist in the selection of appropriate prophylaxis from standardized options. Decision support and clinical reminders have been shown to be more effective when integrated into the workflow19, 24; therefore, a key strategy of our study involved embedding the VTE risk assessment tool and guidance toward appropriate prophylactic regimens into commonly used admission/transfer order sets. We addressed the barriers of physician unfamiliarity or disagreement with guidelines10 with education and consensus‐building sessions with clinical leadership. Clinical feedback from audits, peer review, and nursing‐led interventions rounded out the layered multifaceted interventional approach.

We designed and prospectively validated a VTE RAM during the course of our improvement efforts, and to our knowledge our simple 3‐category (or 3‐level) VTE risk assessment model is the only validated model. The VTE risk assessment/prevention protocol was validated by several important parameters. First, it proved to be practical and easy to use, taking only seconds to complete, and it was readily adopted by all adult medical and surgical services. Second, the VTE RAM demonstrated excellent interobserver agreement for VTE risk level and decisions about adequacy of VTE prophylaxis with 5 physician reviewers. Third, the VTE RAM predicted risk for VTE. All patients suffering from HA VTE were in the moderate‐risk to high‐risk categories, and HA VTE occurred disproportionately in those meeting criteria for high risk. Fourth, implementation of the VTE RAM/protocol resulted in very high, sustained levels of VTE prophylaxis without any detectable safety concerns. Finally and perhaps most importantly, high rates of adherence to the VTE protocol resulted in a 40% decline in the incidence of HA VTE in our institution.

The improved prevalence of adequate VTE prophylaxis reduced, but did not eliminate, HA VTE. The reduction observed is consistent with the 40% to 50% efficacy of prophylaxis reported in the literature.7 Our experience highlights the recent controversy over proposals by the Centers for Medicare & Medicaid Services (CMS) to add HA VTE to the list of do not pay conditions later this year,25 as it is clear from our data that even near‐perfect adherence with accepted VTE prevention measures will not eliminate HA VTE. After vigorous pushback about the fairness of this measure, the HA VTE do not pay scope was narrowed to include only certain major orthopedic procedure patients.

Services with a preponderance of moderate‐risk patients had the largest reduction in HA VTE. Efforts that are focused only on high‐risk orthopedic, trauma, and critical care patients will miss the larger opportunities for maximal reduction in HA VTE for multiple reasons. First, moderate VTE risk patients are far more prevalent than high VTE risk patients (84% vs. 12% of inpatients at our institution). Second, high‐risk patients are already at a baseline relatively high rate of VTE prophylaxis compared to their moderate VTE risk counterparts (83% vs. 53% at our institution). Third, a large portion of patients at high risk for VTE (such as trauma patients) also have the largest prevalence of absolute or relative contraindications to pharmacologic prophylaxis, limiting the effect size of prevention efforts.

Major strengths of this study included ongoing rigorous concurrent measurement of both processes (percent of patients on adequate prophylaxis) and outcomes (HA VTE diagnosed via imaging studies) over a prolonged time period. The robust random sampling of inpatients insured that changes in VTE prophylaxis rates were not due to changes in the distribution of VTE risk or bias potentially introduced from convenience samples. The longitudinal monitoring of imaging study results for VTE cases is vastly superior to using administrative data that is reliant on coding. The recent University Healthsystem Consortium (UHC) benchmarking data on venous thromboembolism were sobering but instructive.26 UHC used administrative discharge codes for VTE in a secondary position to identify patients with HA VTE, which is a common strategy to follow the incidence of HA VTE. The accuracy of identifying surgical patients with an HA VTE was only 60%. Proper use of the present on admission (POA) designation would have improved this to 83%, but 17% of cases either did not occur or had history only with a labor‐intensive manual chart review. Performance was even worse in medical patients, with only a 30% accuracy rate, potentially improved to 79% if accurate POA designation had been used, and 21% of cases identified by administrative methods either did not occur or had history only. In essence, unless an improvement team uses chart review of each case potentially identified as a HA VTE case, the administrative data are not reliable. Concurrent discovery of VTE cases allows for a more accurate and timely chart review, and allows for near real‐time feedback to the responsible treatment team.

The major limitation of this study is inherent in the observational design and the lack of a control population. Other factors besides our VTE‐specific improvement efforts could affect process and outcomes, and reductions in HA VTE could conceivably occur because of changes in the make‐up of the admitted inpatient population. These limitations are mitigated to some degree by several observations. The VTE risk distribution in the randomly sampled inpatient population did not vary significantly from year to year. The number of HA VTE was reduced in 2007 even though the number of patients and patient days at risk for developing VTE went up. The incidence of community‐acquired VTE remained constant over the same time period, highlighting the consistency of our measurement techniques and the VTE risk in the community we serve. Last, the improvements in VTE prophylaxis rates increased at times that correlated well with the introduction of layered interventions, as depicted in Figure 1.

There were several limitations to the internal study on adverse effects of VTE protocol implementation. First, this was a retrospective study, so much of the data collection was dependent upon physician progress notes and discharge summaries. Lack of documentation could have precluded the appropriate diagnosis codes from being assigned. Next, the study population was generated from coding data, so subjectivity could have been introduced during the coding process. Also, a majority of the patients did not fit the study criteria due to discharge with the e934.2 code, because they were found to have an elevated international normalized ratio (INR) after being admitted on warfarin. Finally, chart‐reviewer bias could have affected the results, as the chart reviewer became more proficient at reviewing charts over time. Despite these limitations, the study methodology allowed for screening of a large population for rare events. Bleeding may be a frequent concern with primary thromboprophylaxis, but data from clinical trials and this study help to demonstrate that rates of adverse events from pharmacologic VTE prophylaxis are very rare.

Another potential limitation is raised by the question of whether our methods can be generalized to other sites. Our site is an academic medical center and we have CPOE, which is present in only a small minority of centers. Furthermore, one could question how feasible it is to get institution‐wide consensus for a VTE prevention protocol in settings with heterogenous medical staffs. To address these issues, we used a proven performance improvement framework calling for administrative support, a multidisciplinary improvement team, reliable measures, and a multifaceted approach to interventions. This framework and our experiences have been incorporated into improvement guides27, 28 that have been the centerpiece of the Society of Hospital Medicine VTE Prevention Collaborative improvement efforts in a wide variety of medical environments. The collaborative leadership has observed that success is the rule when this model is followed, in institutions large and small, academic or community, and in both paper and CPOE environments. Not all of these sites use a VTE RAM identical to ours, and there are local nuances to preferred choices of prophylaxis. However, they all incorporated simple VTE risk stratification with only a few levels of risk. Reinforcing the expectation that pharmacologic prophylaxis is indicated for the majority of inpatients is likely more important than the nuances of choices for each risk level.

We demonstrated that dramatic improvement in VTE prophylaxis is achievable, safe, and effective in reducing the incidence of HA VTE. We used scalable, portable methods to make a large and convincing impact on the incidence of HA VTE, while also developing and prospectively validating a VTE RAM. A wide variety of institutions are achieving significant improvement using similar strategies. Future research and improvement efforts should focus on how to accelerate integration of this model across networks of hospitals, leveraging networks with common order sets or information systems. Widespread success in improving VTE prophylaxis would likely have a far‐reaching benefit on morbidity and PE‐related mortality.