Article

Respiratory diseases have varied clinical presentations and are classified as restrictive, obstructive, mixed, or normal. Restrictive lung diseases have reduced lung volumes, either due to an alteration in lung parenchyma or a disease of the pleura, chest wall, or neuromuscular apparatus. If caused by parenchymal lung disease, restrictive lung disorders are accompanied by reduced gas transfer, which may be portrayed clinically by desaturation after exercise. Based on anatomical structures, the causes of lung volume reduction may be intrinsic or extrinsic. Intrinsic causes correspond to diseases of the lung parenchyma, such as idiopathic fibrotic diseases, connective-tissue diseases, drug-induced lung diseases, and other primary diseases of the lungs. Extrinsic causes refer to disorders outside the lungs or extra-pulmonary diseases such as neuromuscular and nonmuscular diseases of the chest wall.¹ For example, obesity and myasthenia gravis can cause restrictive lung diseases, one through mechanical interference of lung expansion and the other through neuromuscular impedance of thoracic cage expansion. All these diseases eventually result in lung restriction, impaired lung function, and respiratory failure. This heterogenicity of disease makes establishing a single severity criterion difficult.

Laboratory testing, imaging studies, and examinations are important for determining the pulmonary disease and its course and progression. The pulmonary function test (PFT), which consists of multiple procedures that are performed depending on the information needed, has been an essential tool in practice for the pulmonologist. The PFT includes spirometry, lung volume measurement, respiratory muscle strength, diffusion capacity, and a broncho-provocation test. Each test has a particular role in assisting the diagnosis and/or follow-up of the patient. Spirometry is frequently used due to its range of dynamic physiological parameters, ease of use, and accessibility. It is used for the diagnosis of pulmonary symptoms, in the assessment of disability, and preoperatory evaluation, including lung resection surgery, assisting in the diagnosis, monitoring, and therapy response of pulmonary diseases.

A systematic approach to PFT interpretation is recommended by several societies, such as the American Thoracic Society (ATS) and the European Respiratory Society (ERS).² The pulmonary function test results must be reproducible and meet established standards to ensure reliable and consistent clinical outcomes. A restrictive respiratory disease is defined by a decrease in total lung capacity (TLC) (< 5% of predicted value) and a normal forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio.² Although other findings—such as a decrease in vital capacity—should prompt an investigation into whether the patient has a possible restrictive respiratory disease, the sole presence of this parameter is not definitive or diagnostic of a restrictive impairment.^2-4 The assessment of severity is typically determined by TLC. Unfortunately, the severity of a restrictive respiratory disease and the degree of patient discomfort do not always correlate when utilizing just TLC. Pulmonary sarcoidosis, for example, is a granulomatous lung disease with a restrictive PFT pattern and a disease burden that may vary over time. Having a more consistent method of grading the severity of the restrictive lung disease may help guide treatment. The modified Medical Research Council (mMRC) scale, a 5-point dyspnea scale, is widely used in assessing the severity of dyspnea in various respiratory conditions, including chronic obstructive pulmonary disease (COPD), where its scores have been associated with patient mortality.^1,5 The goal of this study was to document the associations between objective parameters obtained through PFT and other variables, with an established measurement of dyspnea to assess the severity grade of restrictive lung diseases.

Methods

This retrospective record review at the Veterans Affairs Caribbean Healthcare System (VACHS) in San Juan, Puerto Rico, wasconducted using the Veterans Health Information Systems and Technology Architecture to identify patients with a PFT, including spirometry, that indicated a restrictive ventilator pattern based on the current ATS/ERS Task Force on Lung Function Testing.² Patients were included if they were aged ≥ 21 years, PFT with TLC ≤ 80% predicted, mMRC score documented on PFT, and documented diffusing capacity of the lung for carbon monoxide (DLCO). Patients were excluded if their FEV₁/vital capacity (VC) was < 70% predicted using the largest VC, or no mMRC score was available. All patients meeting the inclusion criteria were considered regardless of comorbidities.

The PFT results of all adult patients, including those performed between June 1, 2013, and January 6, 2016, were submitted to spirometry, and lung volume measurements were analyzed. Sociodemographic information was collected, including sex, ethnicity, age, height, weight, and basal metabolic index. Other data found in PFTs, such as smoking status, smoking in packs/year, mMRC score, predicted TLC value, imaging present (chest X-ray, computed tomography), and hospitalizations and exacerbations within 1 year were collected. In addition, we examined the predicted values for FEV₁, DLCO, and DLCO/VA (calculated using the Ayer equation), FVC (calculated using the Knudson equation), expiratory reserve volume, inspiratory VC, and slow VC. PaO₂, PaCO₂, and Alveolar-arterial gradients also were collected.^6-9 Information about heart failure status was gathered through medical evaluation of notes and cardiac studies. All categorical variables were correlated with Spearman analysis and quantitative variables with average percentages. P values were calculated with analysis of variance.

Of 6461 VACHS patient records reviewed, 415 met the inclusion criteria. Patients were divided according to their mMRC score: 65 had mMRC score of 0, 87 had an mMRC score of 1, 2 had an mMRC score of 2, 146 had an mMRC of 3, and 115 had an mMRC score of 4. The population was primarily male (98.6%) and of Hispanic ethnicity (96.4%), with a mean age of 72 years (Table 1). Most patients (n = 269, 64.0%) were prior smokers, while 135 patients (32.5%) had never smoked, and 11 (2.7%) were current smokers. At baseline, 169 patients (41.4%) had interstitial lung disease, 39 (9.6%) had chest wall disorders, 29 (7.1%) had occupational exposure, 25 (6.1%) had pneumonitis, and 14 (3.4%) had neuromuscular disorders.

There was a statistically significant relationship between mMRC score and hospitalization and FEV₁ but not TLC (Table 2). As mMRC increased, so did hospitalizations: a total of 168 patients (40.5%) were hospitalized; 24 patients (36.9%) had an mMRC score of 0, 30 patients (34.0%) had an mMRC score of 1, 2 patients (100%) had an mMRC score of 2, 54 patients (37.0%) had an mMRC score of 3, and 58 patients (50.0%) had an mMRC score of 4 (P = .04). Mean (SD) TLC values increased as mMRC scores increased. Mean (SD) TLC was 70.5% (33.0) for the entire population; 68.8% (7.2) for patients with an mMRC score of 0, 70.8% (5.8) for patients with an mMRC score of 1, 75.0% (1.4) for patients with an mMRC score of 2, 70.1% (7.2) for patients with an mMRC score of 3, and 71.5% (62.1) for patients with an mMRC score of 4 (P = .10) (Figure 1). There was an associated decrease in mean (SD) FEV₁ with mMRC. Mean (SD) FEV₁ was 76.2% (18.9) for the entire population; 81.7% (19.3) for patients with an mMRC score of 0, 80.9% (18) for patients with an mMRC score of 1, 93.5% (34.6) for patients with an mMRC score of 2, 76.2% (17.1) for patients with an mMRC score of 3, and 69.2% (19.4) for patients with an mMRC score of 4; (P < .001) (Figure 2).

The correlation between mMRC and FEV₁ (r = 0.25, P < .001) was stronger than the correlation between mMRC and TLC (r = 0.15, P < .001). The correlations for DLCO (P < .001), DLCO/VA (P < .001), hemoglobin (P < .02), and PaO₂ (P < .001) were all statistically significant (P < .005), but with no strong identifiable trend.

Discussion

The patient population of this study was primarily older males of Hispanic ethnicity with a history of smoking. There was no association between body mass index or smoking status with worsening dyspnea as measured with mMRC scores. We observed no significant correlation between mMRC scores and various factors such as comorbidities including heart conditions, and epidemiological factors like the etiology of lung disease, including both intrinsic and extrinsic causes. This lack of association was anticipated, as restrictive lung diseases in our study predominantly arose from intrinsic pulmonary etiologies, such as interstitial lung disease. A difference between more hospitalizations and worsening dyspnea was identified. There was a slightly higher correlation between FEV₁ and mMRC scores when compared with TLC and mMRC scores concerning worsening dyspnea, which could indicate that the use of FEV₁ should be preferred over previous recommendations to use TLC.¹⁰ Other guidelines have utilized exercise capacity via the 6-minute walk test as a marker of severity with spirometry values and found that DLCO was correlated with severity.¹¹

The latest ERS/ATS guidelines recommend z scores for grading the severity of obstructive lung diseases but do not recommend them for the diagnosis of restrictive lung diseases.¹² A z score encompasses diverse variables (eg, age, sex, and ethnicity) to provide more uniform and consistent results. Other studies have been done to relate z scores to other spirometry variables with restrictive lung disease. One such study indicates the potential benefit of using FVC alone to grade restrictive lung diseases.¹³ There continues to be great diversity in the interpretation of pulmonary function tests, and we believe the information gathered can provide valuable insight for managing patients with restrictive lung diseases.

Limitations

Only 2 patients reported an mMRC score of 2 in our study. This may have affected statistical outcomes. It also may reveal possible deficits in the efficacy of patient education on the mMRC scale. This study was also limited by its small sample size, single center location, and the distribution of patients that reported an mMRC favored either low or high values. The patients in this study, who were all veterans, may not be representative of other patient populations.

Conclusions

There continue to be few factors associated with the physiological severity of the defective oxygen delivery and reported dyspnea of a patient with restrictive lung disease that allows for an accurate, repeatable grading of severity. Using FEV₁ instead of TLC to determine the severity of a restrictive lung disease should be reconsidered. We could not find any other strong correlation among other factors studied. Further research should be conducted to continue looking for variables that more accurately depict patient dyspnea in restrictive lung disease.

Acknowledgments

This study is based upon work supported by the Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico, and is the result of work supported by Pulmonary & Critical Care Medicine service, with resources and the use of its facilities.

Respiratory diseases have varied clinical presentations and are classified as restrictive, obstructive, mixed, or normal. Restrictive lung diseases have reduced lung volumes, either due to an alteration in lung parenchyma or a disease of the pleura, chest wall, or neuromuscular apparatus. If caused by parenchymal lung disease, restrictive lung disorders are accompanied by reduced gas transfer, which may be portrayed clinically by desaturation after exercise. Based on anatomical structures, the causes of lung volume reduction may be intrinsic or extrinsic. Intrinsic causes correspond to diseases of the lung parenchyma, such as idiopathic fibrotic diseases, connective-tissue diseases, drug-induced lung diseases, and other primary diseases of the lungs. Extrinsic causes refer to disorders outside the lungs or extra-pulmonary diseases such as neuromuscular and nonmuscular diseases of the chest wall.¹ For example, obesity and myasthenia gravis can cause restrictive lung diseases, one through mechanical interference of lung expansion and the other through neuromuscular impedance of thoracic cage expansion. All these diseases eventually result in lung restriction, impaired lung function, and respiratory failure. This heterogenicity of disease makes establishing a single severity criterion difficult.

Laboratory testing, imaging studies, and examinations are important for determining the pulmonary disease and its course and progression. The pulmonary function test (PFT), which consists of multiple procedures that are performed depending on the information needed, has been an essential tool in practice for the pulmonologist. The PFT includes spirometry, lung volume measurement, respiratory muscle strength, diffusion capacity, and a broncho-provocation test. Each test has a particular role in assisting the diagnosis and/or follow-up of the patient. Spirometry is frequently used due to its range of dynamic physiological parameters, ease of use, and accessibility. It is used for the diagnosis of pulmonary symptoms, in the assessment of disability, and preoperatory evaluation, including lung resection surgery, assisting in the diagnosis, monitoring, and therapy response of pulmonary diseases.

A systematic approach to PFT interpretation is recommended by several societies, such as the American Thoracic Society (ATS) and the European Respiratory Society (ERS).² The pulmonary function test results must be reproducible and meet established standards to ensure reliable and consistent clinical outcomes. A restrictive respiratory disease is defined by a decrease in total lung capacity (TLC) (< 5% of predicted value) and a normal forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio.² Although other findings—such as a decrease in vital capacity—should prompt an investigation into whether the patient has a possible restrictive respiratory disease, the sole presence of this parameter is not definitive or diagnostic of a restrictive impairment.^2-4 The assessment of severity is typically determined by TLC. Unfortunately, the severity of a restrictive respiratory disease and the degree of patient discomfort do not always correlate when utilizing just TLC. Pulmonary sarcoidosis, for example, is a granulomatous lung disease with a restrictive PFT pattern and a disease burden that may vary over time. Having a more consistent method of grading the severity of the restrictive lung disease may help guide treatment. The modified Medical Research Council (mMRC) scale, a 5-point dyspnea scale, is widely used in assessing the severity of dyspnea in various respiratory conditions, including chronic obstructive pulmonary disease (COPD), where its scores have been associated with patient mortality.^1,5 The goal of this study was to document the associations between objective parameters obtained through PFT and other variables, with an established measurement of dyspnea to assess the severity grade of restrictive lung diseases.

Methods

This retrospective record review at the Veterans Affairs Caribbean Healthcare System (VACHS) in San Juan, Puerto Rico, wasconducted using the Veterans Health Information Systems and Technology Architecture to identify patients with a PFT, including spirometry, that indicated a restrictive ventilator pattern based on the current ATS/ERS Task Force on Lung Function Testing.² Patients were included if they were aged ≥ 21 years, PFT with TLC ≤ 80% predicted, mMRC score documented on PFT, and documented diffusing capacity of the lung for carbon monoxide (DLCO). Patients were excluded if their FEV₁/vital capacity (VC) was < 70% predicted using the largest VC, or no mMRC score was available. All patients meeting the inclusion criteria were considered regardless of comorbidities.

The PFT results of all adult patients, including those performed between June 1, 2013, and January 6, 2016, were submitted to spirometry, and lung volume measurements were analyzed. Sociodemographic information was collected, including sex, ethnicity, age, height, weight, and basal metabolic index. Other data found in PFTs, such as smoking status, smoking in packs/year, mMRC score, predicted TLC value, imaging present (chest X-ray, computed tomography), and hospitalizations and exacerbations within 1 year were collected. In addition, we examined the predicted values for FEV₁, DLCO, and DLCO/VA (calculated using the Ayer equation), FVC (calculated using the Knudson equation), expiratory reserve volume, inspiratory VC, and slow VC. PaO₂, PaCO₂, and Alveolar-arterial gradients also were collected.^6-9 Information about heart failure status was gathered through medical evaluation of notes and cardiac studies. All categorical variables were correlated with Spearman analysis and quantitative variables with average percentages. P values were calculated with analysis of variance.

Of 6461 VACHS patient records reviewed, 415 met the inclusion criteria. Patients were divided according to their mMRC score: 65 had mMRC score of 0, 87 had an mMRC score of 1, 2 had an mMRC score of 2, 146 had an mMRC of 3, and 115 had an mMRC score of 4. The population was primarily male (98.6%) and of Hispanic ethnicity (96.4%), with a mean age of 72 years (Table 1). Most patients (n = 269, 64.0%) were prior smokers, while 135 patients (32.5%) had never smoked, and 11 (2.7%) were current smokers. At baseline, 169 patients (41.4%) had interstitial lung disease, 39 (9.6%) had chest wall disorders, 29 (7.1%) had occupational exposure, 25 (6.1%) had pneumonitis, and 14 (3.4%) had neuromuscular disorders.

There was a statistically significant relationship between mMRC score and hospitalization and FEV₁ but not TLC (Table 2). As mMRC increased, so did hospitalizations: a total of 168 patients (40.5%) were hospitalized; 24 patients (36.9%) had an mMRC score of 0, 30 patients (34.0%) had an mMRC score of 1, 2 patients (100%) had an mMRC score of 2, 54 patients (37.0%) had an mMRC score of 3, and 58 patients (50.0%) had an mMRC score of 4 (P = .04). Mean (SD) TLC values increased as mMRC scores increased. Mean (SD) TLC was 70.5% (33.0) for the entire population; 68.8% (7.2) for patients with an mMRC score of 0, 70.8% (5.8) for patients with an mMRC score of 1, 75.0% (1.4) for patients with an mMRC score of 2, 70.1% (7.2) for patients with an mMRC score of 3, and 71.5% (62.1) for patients with an mMRC score of 4 (P = .10) (Figure 1). There was an associated decrease in mean (SD) FEV₁ with mMRC. Mean (SD) FEV₁ was 76.2% (18.9) for the entire population; 81.7% (19.3) for patients with an mMRC score of 0, 80.9% (18) for patients with an mMRC score of 1, 93.5% (34.6) for patients with an mMRC score of 2, 76.2% (17.1) for patients with an mMRC score of 3, and 69.2% (19.4) for patients with an mMRC score of 4; (P < .001) (Figure 2).

The correlation between mMRC and FEV₁ (r = 0.25, P < .001) was stronger than the correlation between mMRC and TLC (r = 0.15, P < .001). The correlations for DLCO (P < .001), DLCO/VA (P < .001), hemoglobin (P < .02), and PaO₂ (P < .001) were all statistically significant (P < .005), but with no strong identifiable trend.

Discussion

The patient population of this study was primarily older males of Hispanic ethnicity with a history of smoking. There was no association between body mass index or smoking status with worsening dyspnea as measured with mMRC scores. We observed no significant correlation between mMRC scores and various factors such as comorbidities including heart conditions, and epidemiological factors like the etiology of lung disease, including both intrinsic and extrinsic causes. This lack of association was anticipated, as restrictive lung diseases in our study predominantly arose from intrinsic pulmonary etiologies, such as interstitial lung disease. A difference between more hospitalizations and worsening dyspnea was identified. There was a slightly higher correlation between FEV₁ and mMRC scores when compared with TLC and mMRC scores concerning worsening dyspnea, which could indicate that the use of FEV₁ should be preferred over previous recommendations to use TLC.¹⁰ Other guidelines have utilized exercise capacity via the 6-minute walk test as a marker of severity with spirometry values and found that DLCO was correlated with severity.¹¹

The latest ERS/ATS guidelines recommend z scores for grading the severity of obstructive lung diseases but do not recommend them for the diagnosis of restrictive lung diseases.¹² A z score encompasses diverse variables (eg, age, sex, and ethnicity) to provide more uniform and consistent results. Other studies have been done to relate z scores to other spirometry variables with restrictive lung disease. One such study indicates the potential benefit of using FVC alone to grade restrictive lung diseases.¹³ There continues to be great diversity in the interpretation of pulmonary function tests, and we believe the information gathered can provide valuable insight for managing patients with restrictive lung diseases.

Limitations

Only 2 patients reported an mMRC score of 2 in our study. This may have affected statistical outcomes. It also may reveal possible deficits in the efficacy of patient education on the mMRC scale. This study was also limited by its small sample size, single center location, and the distribution of patients that reported an mMRC favored either low or high values. The patients in this study, who were all veterans, may not be representative of other patient populations.

Conclusions

There continue to be few factors associated with the physiological severity of the defective oxygen delivery and reported dyspnea of a patient with restrictive lung disease that allows for an accurate, repeatable grading of severity. Using FEV₁ instead of TLC to determine the severity of a restrictive lung disease should be reconsidered. We could not find any other strong correlation among other factors studied. Further research should be conducted to continue looking for variables that more accurately depict patient dyspnea in restrictive lung disease.

Acknowledgments

This study is based upon work supported by the Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico, and is the result of work supported by Pulmonary & Critical Care Medicine service, with resources and the use of its facilities.

Respiratory diseases have varied clinical presentations and are classified as restrictive, obstructive, mixed, or normal. Restrictive lung diseases have reduced lung volumes, either due to an alteration in lung parenchyma or a disease of the pleura, chest wall, or neuromuscular apparatus. If caused by parenchymal lung disease, restrictive lung disorders are accompanied by reduced gas transfer, which may be portrayed clinically by desaturation after exercise. Based on anatomical structures, the causes of lung volume reduction may be intrinsic or extrinsic. Intrinsic causes correspond to diseases of the lung parenchyma, such as idiopathic fibrotic diseases, connective-tissue diseases, drug-induced lung diseases, and other primary diseases of the lungs. Extrinsic causes refer to disorders outside the lungs or extra-pulmonary diseases such as neuromuscular and nonmuscular diseases of the chest wall.¹ For example, obesity and myasthenia gravis can cause restrictive lung diseases, one through mechanical interference of lung expansion and the other through neuromuscular impedance of thoracic cage expansion. All these diseases eventually result in lung restriction, impaired lung function, and respiratory failure. This heterogenicity of disease makes establishing a single severity criterion difficult.

Laboratory testing, imaging studies, and examinations are important for determining the pulmonary disease and its course and progression. The pulmonary function test (PFT), which consists of multiple procedures that are performed depending on the information needed, has been an essential tool in practice for the pulmonologist. The PFT includes spirometry, lung volume measurement, respiratory muscle strength, diffusion capacity, and a broncho-provocation test. Each test has a particular role in assisting the diagnosis and/or follow-up of the patient. Spirometry is frequently used due to its range of dynamic physiological parameters, ease of use, and accessibility. It is used for the diagnosis of pulmonary symptoms, in the assessment of disability, and preoperatory evaluation, including lung resection surgery, assisting in the diagnosis, monitoring, and therapy response of pulmonary diseases.

A systematic approach to PFT interpretation is recommended by several societies, such as the American Thoracic Society (ATS) and the European Respiratory Society (ERS).² The pulmonary function test results must be reproducible and meet established standards to ensure reliable and consistent clinical outcomes. A restrictive respiratory disease is defined by a decrease in total lung capacity (TLC) (< 5% of predicted value) and a normal forced expiratory volume in 1 second (FEV₁)/forced vital capacity (FVC) ratio.² Although other findings—such as a decrease in vital capacity—should prompt an investigation into whether the patient has a possible restrictive respiratory disease, the sole presence of this parameter is not definitive or diagnostic of a restrictive impairment.^2-4 The assessment of severity is typically determined by TLC. Unfortunately, the severity of a restrictive respiratory disease and the degree of patient discomfort do not always correlate when utilizing just TLC. Pulmonary sarcoidosis, for example, is a granulomatous lung disease with a restrictive PFT pattern and a disease burden that may vary over time. Having a more consistent method of grading the severity of the restrictive lung disease may help guide treatment. The modified Medical Research Council (mMRC) scale, a 5-point dyspnea scale, is widely used in assessing the severity of dyspnea in various respiratory conditions, including chronic obstructive pulmonary disease (COPD), where its scores have been associated with patient mortality.^1,5 The goal of this study was to document the associations between objective parameters obtained through PFT and other variables, with an established measurement of dyspnea to assess the severity grade of restrictive lung diseases.

Methods

This retrospective record review at the Veterans Affairs Caribbean Healthcare System (VACHS) in San Juan, Puerto Rico, wasconducted using the Veterans Health Information Systems and Technology Architecture to identify patients with a PFT, including spirometry, that indicated a restrictive ventilator pattern based on the current ATS/ERS Task Force on Lung Function Testing.² Patients were included if they were aged ≥ 21 years, PFT with TLC ≤ 80% predicted, mMRC score documented on PFT, and documented diffusing capacity of the lung for carbon monoxide (DLCO). Patients were excluded if their FEV₁/vital capacity (VC) was < 70% predicted using the largest VC, or no mMRC score was available. All patients meeting the inclusion criteria were considered regardless of comorbidities.

The PFT results of all adult patients, including those performed between June 1, 2013, and January 6, 2016, were submitted to spirometry, and lung volume measurements were analyzed. Sociodemographic information was collected, including sex, ethnicity, age, height, weight, and basal metabolic index. Other data found in PFTs, such as smoking status, smoking in packs/year, mMRC score, predicted TLC value, imaging present (chest X-ray, computed tomography), and hospitalizations and exacerbations within 1 year were collected. In addition, we examined the predicted values for FEV₁, DLCO, and DLCO/VA (calculated using the Ayer equation), FVC (calculated using the Knudson equation), expiratory reserve volume, inspiratory VC, and slow VC. PaO₂, PaCO₂, and Alveolar-arterial gradients also were collected.^6-9 Information about heart failure status was gathered through medical evaluation of notes and cardiac studies. All categorical variables were correlated with Spearman analysis and quantitative variables with average percentages. P values were calculated with analysis of variance.

Of 6461 VACHS patient records reviewed, 415 met the inclusion criteria. Patients were divided according to their mMRC score: 65 had mMRC score of 0, 87 had an mMRC score of 1, 2 had an mMRC score of 2, 146 had an mMRC of 3, and 115 had an mMRC score of 4. The population was primarily male (98.6%) and of Hispanic ethnicity (96.4%), with a mean age of 72 years (Table 1). Most patients (n = 269, 64.0%) were prior smokers, while 135 patients (32.5%) had never smoked, and 11 (2.7%) were current smokers. At baseline, 169 patients (41.4%) had interstitial lung disease, 39 (9.6%) had chest wall disorders, 29 (7.1%) had occupational exposure, 25 (6.1%) had pneumonitis, and 14 (3.4%) had neuromuscular disorders.

There was a statistically significant relationship between mMRC score and hospitalization and FEV₁ but not TLC (Table 2). As mMRC increased, so did hospitalizations: a total of 168 patients (40.5%) were hospitalized; 24 patients (36.9%) had an mMRC score of 0, 30 patients (34.0%) had an mMRC score of 1, 2 patients (100%) had an mMRC score of 2, 54 patients (37.0%) had an mMRC score of 3, and 58 patients (50.0%) had an mMRC score of 4 (P = .04). Mean (SD) TLC values increased as mMRC scores increased. Mean (SD) TLC was 70.5% (33.0) for the entire population; 68.8% (7.2) for patients with an mMRC score of 0, 70.8% (5.8) for patients with an mMRC score of 1, 75.0% (1.4) for patients with an mMRC score of 2, 70.1% (7.2) for patients with an mMRC score of 3, and 71.5% (62.1) for patients with an mMRC score of 4 (P = .10) (Figure 1). There was an associated decrease in mean (SD) FEV₁ with mMRC. Mean (SD) FEV₁ was 76.2% (18.9) for the entire population; 81.7% (19.3) for patients with an mMRC score of 0, 80.9% (18) for patients with an mMRC score of 1, 93.5% (34.6) for patients with an mMRC score of 2, 76.2% (17.1) for patients with an mMRC score of 3, and 69.2% (19.4) for patients with an mMRC score of 4; (P < .001) (Figure 2).

The correlation between mMRC and FEV₁ (r = 0.25, P < .001) was stronger than the correlation between mMRC and TLC (r = 0.15, P < .001). The correlations for DLCO (P < .001), DLCO/VA (P < .001), hemoglobin (P < .02), and PaO₂ (P < .001) were all statistically significant (P < .005), but with no strong identifiable trend.

Discussion

The patient population of this study was primarily older males of Hispanic ethnicity with a history of smoking. There was no association between body mass index or smoking status with worsening dyspnea as measured with mMRC scores. We observed no significant correlation between mMRC scores and various factors such as comorbidities including heart conditions, and epidemiological factors like the etiology of lung disease, including both intrinsic and extrinsic causes. This lack of association was anticipated, as restrictive lung diseases in our study predominantly arose from intrinsic pulmonary etiologies, such as interstitial lung disease. A difference between more hospitalizations and worsening dyspnea was identified. There was a slightly higher correlation between FEV₁ and mMRC scores when compared with TLC and mMRC scores concerning worsening dyspnea, which could indicate that the use of FEV₁ should be preferred over previous recommendations to use TLC.¹⁰ Other guidelines have utilized exercise capacity via the 6-minute walk test as a marker of severity with spirometry values and found that DLCO was correlated with severity.¹¹

The latest ERS/ATS guidelines recommend z scores for grading the severity of obstructive lung diseases but do not recommend them for the diagnosis of restrictive lung diseases.¹² A z score encompasses diverse variables (eg, age, sex, and ethnicity) to provide more uniform and consistent results. Other studies have been done to relate z scores to other spirometry variables with restrictive lung disease. One such study indicates the potential benefit of using FVC alone to grade restrictive lung diseases.¹³ There continues to be great diversity in the interpretation of pulmonary function tests, and we believe the information gathered can provide valuable insight for managing patients with restrictive lung diseases.

Limitations

Only 2 patients reported an mMRC score of 2 in our study. This may have affected statistical outcomes. It also may reveal possible deficits in the efficacy of patient education on the mMRC scale. This study was also limited by its small sample size, single center location, and the distribution of patients that reported an mMRC favored either low or high values. The patients in this study, who were all veterans, may not be representative of other patient populations.

Conclusions

There continue to be few factors associated with the physiological severity of the defective oxygen delivery and reported dyspnea of a patient with restrictive lung disease that allows for an accurate, repeatable grading of severity. Using FEV₁ instead of TLC to determine the severity of a restrictive lung disease should be reconsidered. We could not find any other strong correlation among other factors studied. Further research should be conducted to continue looking for variables that more accurately depict patient dyspnea in restrictive lung disease.

Acknowledgments

This study is based upon work supported by the Veterans Affairs Caribbean Healthcare System in San Juan, Puerto Rico, and is the result of work supported by Pulmonary & Critical Care Medicine service, with resources and the use of its facilities.

Increasing complexities within health care systems are significant impediments to the consistent delivery of safe and effective patient care. These impediments include an increase in specialization of care, staff shortages, burnout, poor coordination of services and access to care, as well as rising costs.¹ High reliability organizations (HROs) provide safe, high-quality, and effective care in highly complex and risk-prone environments without causing harm or experiencing catastrophic events.²

Within the US Department of Veterans Affairs (VA), the Veterans Health Administration (VHA) operates the nation’s largest integrated health care system, providing care to > 9 million veterans. The VHA formally launched plans for an enterprise-wide HRO in February 2019. During the first year, 18 medical facilities comprised cohort1 of the journey to high reliability. Cohort 2 began in October 2020 and consisted of 54 facilities. Cohort 3 started in October 2021 with 67 facilities.³

Health care organizations seeking high reliability exercise a philosophy aimed at learning from errors and addressing system failures. High reliability is accomplished by implementing 5 principles: (1) sensitivity to operations (a heightened understanding of the current state of systems); (2) preoccupation with failure (striving to anticipate risks that might suggest a much larger system problem); (3) reluctance to simplify (avoiding making any assumptions regarding the causes of failures); (4) commitment to resilience (preparing for potential failures and bouncing back when they occur); and (5) deference to expertise (deferring to individuals with the skills and proficiency to make the best decisions).² The VHA also recognized that a successful journey to high reliability—in addition to achieving a culture of safety—relies on the implementation of foundational HRO practices: leader rounding, visual management systems, safety forums, and safety huddles. This article describes an initiative for how these foundational practices were implemented in a large integrated health care system.

BACKGROUND

The VHA has focused on 4 foundational components as part of its enterprise activities and support structure to implement HRO principles and practices. These components were selected based on pilot activities that preceded the enterprise-wide effort, reviews of the literature, and expert consultation with both government and private sector health systems. To support the implementation of these practices, the VHA provided training, toolkits, HRO executive leader coaching, and peer-to-peer mentoring. As the VHA enters its fifth year seeking high reliability, we undertook an initiative to reflect on our own experiences and refine our practices based on an updated literature review.

As part of this enterprise-wide initiative, we conducted a literature review from 2018 to March 2023 seeking recent evidence describing the value of implementing the 4 foundational HRO practices to advance high reliability and improve patient safety. A 5-year period was used to ensure recency and value of evidence.

Eligible literature was identified in PubMed, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, Scopus, the Cochrane Library, and ProQuest Dissertations & Theses Global. Inclusion and exclusion criteria were peer-reviewed interdisciplinary documents(eg, publications, dissertations, conference proceedings, and grey literature) written in English. Search terms included high reliability organizations, foundational practices, and patient safety. Boolean operators (AND, OR) were also used in the search. The search resulted in a dearth of evidence that addressed implementation of all 4 foundational practices across a health care system. Retrieved evidence focused on the implementation of only 1 particular foundational practice in a specific health care setting. In addition to describing the formal processes for the implementation of each foundational HRO practice, a brief description of representative examples of strong practices within the VHA is provided.

To support the implementation of HROs, the VHA paired HRO executive leader coaches with select medical center directors and their leadership teams. Executive leader coaches also support an organization’s HRO Lead and HRO Champion. The HRO Lead coordinates and facilitates the implementation of HRO principles and practices in pursuit of no harm across an organization. The HRO Champion supports the same as the HRO Lead, but typically has a different specialty background. For example, if the HRO Lead has an administrative background, the HRO Champion would have a clinical background.

Coaching focuses heavily on supporting site-specific implementation and sustainment of the 4 HRO foundational practices. The aim is to accelerate change, build enduring capacity, foster a safety culture, and accelerate HRO maturity. To measure change, HRO executive leader coaches track the progress of their aligned VA medical centers (VAMCs) using the Organizational Learning Tool (OLT). This tool was developed to provide information such as a facility summary and relationships between a medical center director, HRO Lead, HRO Champion, and the executive leader coach (Figure 1). The OLT also serves as a structured process to measure leader coaching performance against mutually agreed upon objectives that ultimately contribute to enterprise outcomes. It also collects data on the progress in implementing foundational practices, strong practices, needs and gaps, and more (Figure 2). Data collected from facilities supported by HRO executive leader coaches on whether foundational practices are in place are briefly described.

Leader Rounding

Leader rounding for high reliability ensures effective, bidirectional communication and collaboration among all disciplines to improve patient safety. It is an essential feature of a robust patient safety culture and an important method for demonstrating leadership engagement with high reliability.^4,5 These rounds are conducted by organizational leadership (eg, executive teams, department/service chiefs, or unit managers) and frontline staff from different areas. They are specifically focused on high reliability, patient and staff safety, and improvement efforts. The aim is to learn about daily challenges that may contribute to patient harm.⁴

Leader rounding has been found to be highly effective at improving leadership visibility across the organization. It enhances interaction and open communication with frontline staff, fostering leader-staff collaboration and shared decision-making,as well as promoting leadership understanding of operational, clinical, nonclinical (eg, administrative, nutrition services, or facilities management), and patient/family experience issues.⁴ Collaboration among team members fosters the delivery of more effective and efficient care, increases staff satisfaction, and improves employee retention.⁶ Leader rounding for high reliability significantly contributes to the breakdown of power barriers by giving team members voice and agency, ultimately leading to deeper engagement.⁷

It is important that leader rounding for high reliability occurs as planned and when possible, scheduled in advance. This helps to avoid rounding at peak times when care activities are being performed.^4,6 When scheduling conflicts arise, another leader should be sent to participate in rounds.⁴ Developing a list of questions in advance allows leadership to prepare messaging to share with staff as it relates to high reliability and patient safety (Table).^4,6,8

Closing the loop improves bidirectional communication and is critical to leader rounding for high reliability. Closed-loop communication and following up on and/or closing out issues raised during rounding empowers the sharing of information, which is critical for advancing a culture of safety.^4,8 Enhanced feedback is also associated with greater workforce engagement, staff feeling more connected to quality improvement activities, and lower rates of employee burnout.⁷ It is important to recognize that senior leaders are not responsible for resolving all issues. If a team or manager can resolve concerns that are raised, this should be encouraged and supported. Maintaining accountability at the lowest level of the organization promotes principles and practices of high reliability (Figure 3).^4,8

The VA Bedford Healthcare System created and implemented a strong practice for leader rounding for high reliability. This phased implementation involved creating an evidence-based process, deciding on an appropriate cadence, developing a tracking tool, and measuring impact to determine the overall effectiveness of leader rounding for high reliability.⁴

A visual management system (VMS) displays clinical and operational performance aligned with HRO goals and practices. It is used to view and guide discussions between interdisciplinary teams during tiered safety huddles, leader rounds for high reliability, and frontline staff on the current status and safety trends in a particular area.^8,9 A VMS is highly effective in creating an environment where all staff members, especially frontline workers, feel empowered to voice their concerns related to safety or to identify improvement opportunities.^8,10 Increased leader engagement in patient safety and heightened transparency of information associated with the use of a VMS improves staff morale and professional satisfaction.¹⁰

A VMS may be a dry-erase or whiteboard display, paper-based display, or electronic status board.⁸ VMSs are usually located in or near work settings (eg, nurses’ station, staff break room, or conference room).⁸ Although they can take different forms and display several types of information, a VMS should be easy to update and meet the specific needs of a work area. In the VHA, a VMS displays: (1) essential information for staff members to effectively perform their work; (2) improvement project ideas; (3) current work in progress; (4) tracking of implemented improvement activities; (5) strong practices that have been effective; and (6) staff recognition for those who have enhanced patient safety, including the reporting of close calls and near misses.

The VHA uses the MESS (methods, equipment, staffing, and supplies) VMS format. This format empowers staff to identify whether proper procedures and practices are in place, essential equipment and supplies are readily available in the quantity needed, and appropriate staffing is on hand to provide safe, high-quality patient care.⁸ Colored magnets are used as visual cues in a stoplight classification system to identify low or no safety risks (green), at risk (yellow), or high risk (red). Green coded issues are addressed locally by a manager or supervisor. Yellow coded concerns require increased staff and leadership vigilance. Red coded issues indicate that patient care would be impacted that day and therefore need to be immediately escalated and addressed with senior leaders to mitigate the threat.^4,11 Dayton VAMC successfully implemented a VMS, using both physical and electronic visual management boards. The Dayton VAMC VMS boards are closely tied to tiered safety huddles and leader rounding for high reliability.   

Safety Forums

Safety forums are another foundational practice of VHA health care organizations seeking high reliability. Recurring monthly, safety forums focus on reinforcing HRO principles and practices, safety programs, the importance and appreciation of reporting, and just culture. The emphasis on just culture reminds staff that adverse events in the organization are viewed as valuable learning opportunities to understand the factors leading to the situation as opposed to immediately assigning blame.¹²

Psychological safety is another important focus. When individuals feel psychologically safe, they are more likely to voice concerns and act without fear of reprisal, which supports a culture of safety.¹³ Safety forums are open to all members of the health care organization, including both clinical and nonclinical staff. Forums can be conducted by an HRO Lead, HRO Champion, Patient Safety Manager, or even executive leadership. Rotating the responsibility of leading these forums demonstrates that high reliability and safety are everyone’s responsibility.

Safety forums publicly review and discuss errors, adverse events, close calls, and near misses. Time is also spent discussing root cause analysis trends and highlighting continuous process improvement principles and current projects. During safety forums, leaders should recognize individuals for safety behaviors and reward reporting through a safety awards program.¹⁴ All forums should conclude with a question-and-answer session. Forums typically occur in virtual 30-minute sessionsbut can last up to 60 minutes when guest speakers attend and continuing education credit is offered.

The Jesse Brown VAMC in Chicago developed an interactive monthly safety forum appealing to a broad audience. Each forum is attended by about 200 staff members and includes leader engagement and panel discussions led by the chief medical officer, with topics on both patient and team safety connecting with HRO principles. A planning committee prepares guest speakers and offers continuing education credits.

Based on the processes of high reliability industries like aviation and nuclear power, tiered safety huddles have been increasingly adopted in health care. Huddles (health care, utilizing, deliberate, discussion,linking, and events) are department-level interdisciplinary meetings that last no more than 15 minutes.¹⁵ Their purpose is to improve communication by sharing day-to-day information across multiple disciplines, identify issues that may impact the delivery of care (eg, patient and staff safety concerns, staffing issues, or inadequate supplies) and resolve problems.

Tiered safety huddles are gaining popularity, especially in organizations seeking high reliability. They are more complex than traditional huddles because of the mechanics of elevating safety issues (eg, bedside to executive leadership teams), feedback loops, and sequencing, among other factors.^15,16

Tiered safety huddles are focused, transparent forums with multidisciplinary staff, including frontline workers, along with senior leadership.^15,16 When initially implemented, tiered safety huddles may take longer than the suggested 15 minutes; however, as teams become more experienced, huddles become more efficient.¹⁵ The goal of tiered safety huddles is to proactively identify, share, address, and resolve problems that have the potential to impact the delivery of safe and quality patient care. This may include addressing staffing shortfalls, inadequate allocation of supplies and equipment, operational issues, etc.^8,15 Critical to theeffective utilization of tiered safety huddles is the appropriate escalation of issues between tiers. The most critical issues are elevated to higher tiers so they are addressed by the most qualified person in the organization.

Deciding on the number of tiers typically depends on the size and scope of services provided by the health care organization or integrated system.For example, tiered huddles in the VHA originate at the point of service (eg, critical care unit). Tier 1 includes staff members at the unit/team level along with immediate supervisors/managers. Tier 2 involves departments and service lines (eg, pharmacy, podiatry, or internal medicine) including their respective leadership. Tier 3 is the executive leadership team. This process allows for bidirectional communication instead of the traditional hierarchical communication pathway (Figure 4). Issues identified that cannot be addressed at a particular tier are elevated to the next tier. Elevated issues typically involve systems or processes requiring attention and resolution by senior leadership.¹⁵ Tier 4 huddles at the Veterans Integrated Services Network level and Tier 5 huddles at the VHA Central Office level are being initiated. These additional levels will more effectively identify system-level risks and issues that may impact multiple VHA facilities and may be addressed through centralized functions and resources.

Tiered safety huddles have been found to be instrumental to ensuring the flow of information across organizations, improving multidisciplinary and leadership engagement and collaboration, as well as increasing accountability for safety.Tiered safety huddles increase situational awareness, which improves an organization’s ability to appropriately respond to safety concerns.Furthermore, tiered safety huddles enhance teamwork and interprofessional collaboration, and have been found to significantly increase the reporting of patient safety events.^15-19

The VA Connecticut Healthcare System tiered huddles followed a pilot testing implementation process. After receiving executive-level commitment, an evidence-based process was enacted, including staff education, selecting a VMS, determining tier interaction, and deciding on metrics to track.¹⁵

Implementing Foundational Practices

To examine the progress of the implementation of the 4 foundational HRO practices, quarterly metrics derived from the OLT are reviewed to determine whether each is being implemented and sustained. The OLT also tracks progress over time. For example, at the 27 cohort 2 and lead sites that initiated leader coaching in 2021 and continued through 2022, coaches observed a 27% increase in leader rounding for high reliability and a 46% increase in the use of VMSs. For the 66 cohort 3 sites that began leader coaching in 2022, coaches documented similar changes, ranging from a 40% increase in leader rounding for high reliability to a 66% increase in the use of safety forums. Additional data continue to be collected and analyzed to publish more comprehensive findings.

DISCUSSION

Incorporating leader rounding for high reliability, VMSs, safety forums, and tiered safety huddles into daily operations is critical to building and sustaining a robust culture of safety.⁸ The 4 foundational HRO practices are instrumental in providing psychologically safe forums for staff to share concerns and actively participate. These practices also promote continual, efficient bidirectional communication throughout organizational lines and across services. The increased visibility and transparency of leaders demonstrate the importance of fostering trust, enhancing closed-loop communication with issues that arise, and building momentum to achieve high reliability. The interconnectedness of the foundational HRO practices identified and implemented by the VHA helps foster teamwork and collaboration built on trust, respect, enthusiasm for improvement, and the delivery of exceptional patient care.

CONCLUSIONS

Incorporating the 4 foundational practices into daily operations is beneficial to the delivery of safe, high-quality health care. This effective and sustained application can strengthen a health care organization on its journey to high reliability and establishing a culture of safety. To be effective, these foundational practices should be personalized to support the unique circumstances of every health care environment. While the exact methodology by which organizations implement these practices may differ, they will help organizations approach patient safety in a more transparent and thoughtful manner.

Acknowledgments

The authors thank Aaron M. Sawyer, PhD, PMP, and Jessica Fankhauser, MA, for their unwavering administrative support, and Jeff Wright for exceptional graphic design support.

Increasing complexities within health care systems are significant impediments to the consistent delivery of safe and effective patient care. These impediments include an increase in specialization of care, staff shortages, burnout, poor coordination of services and access to care, as well as rising costs.¹ High reliability organizations (HROs) provide safe, high-quality, and effective care in highly complex and risk-prone environments without causing harm or experiencing catastrophic events.²

Within the US Department of Veterans Affairs (VA), the Veterans Health Administration (VHA) operates the nation’s largest integrated health care system, providing care to > 9 million veterans. The VHA formally launched plans for an enterprise-wide HRO in February 2019. During the first year, 18 medical facilities comprised cohort1 of the journey to high reliability. Cohort 2 began in October 2020 and consisted of 54 facilities. Cohort 3 started in October 2021 with 67 facilities.³

Health care organizations seeking high reliability exercise a philosophy aimed at learning from errors and addressing system failures. High reliability is accomplished by implementing 5 principles: (1) sensitivity to operations (a heightened understanding of the current state of systems); (2) preoccupation with failure (striving to anticipate risks that might suggest a much larger system problem); (3) reluctance to simplify (avoiding making any assumptions regarding the causes of failures); (4) commitment to resilience (preparing for potential failures and bouncing back when they occur); and (5) deference to expertise (deferring to individuals with the skills and proficiency to make the best decisions).² The VHA also recognized that a successful journey to high reliability—in addition to achieving a culture of safety—relies on the implementation of foundational HRO practices: leader rounding, visual management systems, safety forums, and safety huddles. This article describes an initiative for how these foundational practices were implemented in a large integrated health care system.

BACKGROUND

The VHA has focused on 4 foundational components as part of its enterprise activities and support structure to implement HRO principles and practices. These components were selected based on pilot activities that preceded the enterprise-wide effort, reviews of the literature, and expert consultation with both government and private sector health systems. To support the implementation of these practices, the VHA provided training, toolkits, HRO executive leader coaching, and peer-to-peer mentoring. As the VHA enters its fifth year seeking high reliability, we undertook an initiative to reflect on our own experiences and refine our practices based on an updated literature review.

As part of this enterprise-wide initiative, we conducted a literature review from 2018 to March 2023 seeking recent evidence describing the value of implementing the 4 foundational HRO practices to advance high reliability and improve patient safety. A 5-year period was used to ensure recency and value of evidence.

Eligible literature was identified in PubMed, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, Scopus, the Cochrane Library, and ProQuest Dissertations & Theses Global. Inclusion and exclusion criteria were peer-reviewed interdisciplinary documents(eg, publications, dissertations, conference proceedings, and grey literature) written in English. Search terms included high reliability organizations, foundational practices, and patient safety. Boolean operators (AND, OR) were also used in the search. The search resulted in a dearth of evidence that addressed implementation of all 4 foundational practices across a health care system. Retrieved evidence focused on the implementation of only 1 particular foundational practice in a specific health care setting. In addition to describing the formal processes for the implementation of each foundational HRO practice, a brief description of representative examples of strong practices within the VHA is provided.

To support the implementation of HROs, the VHA paired HRO executive leader coaches with select medical center directors and their leadership teams. Executive leader coaches also support an organization’s HRO Lead and HRO Champion. The HRO Lead coordinates and facilitates the implementation of HRO principles and practices in pursuit of no harm across an organization. The HRO Champion supports the same as the HRO Lead, but typically has a different specialty background. For example, if the HRO Lead has an administrative background, the HRO Champion would have a clinical background.

Coaching focuses heavily on supporting site-specific implementation and sustainment of the 4 HRO foundational practices. The aim is to accelerate change, build enduring capacity, foster a safety culture, and accelerate HRO maturity. To measure change, HRO executive leader coaches track the progress of their aligned VA medical centers (VAMCs) using the Organizational Learning Tool (OLT). This tool was developed to provide information such as a facility summary and relationships between a medical center director, HRO Lead, HRO Champion, and the executive leader coach (Figure 1). The OLT also serves as a structured process to measure leader coaching performance against mutually agreed upon objectives that ultimately contribute to enterprise outcomes. It also collects data on the progress in implementing foundational practices, strong practices, needs and gaps, and more (Figure 2). Data collected from facilities supported by HRO executive leader coaches on whether foundational practices are in place are briefly described.

Leader Rounding

Leader rounding for high reliability ensures effective, bidirectional communication and collaboration among all disciplines to improve patient safety. It is an essential feature of a robust patient safety culture and an important method for demonstrating leadership engagement with high reliability.^4,5 These rounds are conducted by organizational leadership (eg, executive teams, department/service chiefs, or unit managers) and frontline staff from different areas. They are specifically focused on high reliability, patient and staff safety, and improvement efforts. The aim is to learn about daily challenges that may contribute to patient harm.⁴

Leader rounding has been found to be highly effective at improving leadership visibility across the organization. It enhances interaction and open communication with frontline staff, fostering leader-staff collaboration and shared decision-making,as well as promoting leadership understanding of operational, clinical, nonclinical (eg, administrative, nutrition services, or facilities management), and patient/family experience issues.⁴ Collaboration among team members fosters the delivery of more effective and efficient care, increases staff satisfaction, and improves employee retention.⁶ Leader rounding for high reliability significantly contributes to the breakdown of power barriers by giving team members voice and agency, ultimately leading to deeper engagement.⁷

It is important that leader rounding for high reliability occurs as planned and when possible, scheduled in advance. This helps to avoid rounding at peak times when care activities are being performed.^4,6 When scheduling conflicts arise, another leader should be sent to participate in rounds.⁴ Developing a list of questions in advance allows leadership to prepare messaging to share with staff as it relates to high reliability and patient safety (Table).^4,6,8

Closing the loop improves bidirectional communication and is critical to leader rounding for high reliability. Closed-loop communication and following up on and/or closing out issues raised during rounding empowers the sharing of information, which is critical for advancing a culture of safety.^4,8 Enhanced feedback is also associated with greater workforce engagement, staff feeling more connected to quality improvement activities, and lower rates of employee burnout.⁷ It is important to recognize that senior leaders are not responsible for resolving all issues. If a team or manager can resolve concerns that are raised, this should be encouraged and supported. Maintaining accountability at the lowest level of the organization promotes principles and practices of high reliability (Figure 3).^4,8

The VA Bedford Healthcare System created and implemented a strong practice for leader rounding for high reliability. This phased implementation involved creating an evidence-based process, deciding on an appropriate cadence, developing a tracking tool, and measuring impact to determine the overall effectiveness of leader rounding for high reliability.⁴

A visual management system (VMS) displays clinical and operational performance aligned with HRO goals and practices. It is used to view and guide discussions between interdisciplinary teams during tiered safety huddles, leader rounds for high reliability, and frontline staff on the current status and safety trends in a particular area.^8,9 A VMS is highly effective in creating an environment where all staff members, especially frontline workers, feel empowered to voice their concerns related to safety or to identify improvement opportunities.^8,10 Increased leader engagement in patient safety and heightened transparency of information associated with the use of a VMS improves staff morale and professional satisfaction.¹⁰

A VMS may be a dry-erase or whiteboard display, paper-based display, or electronic status board.⁸ VMSs are usually located in or near work settings (eg, nurses’ station, staff break room, or conference room).⁸ Although they can take different forms and display several types of information, a VMS should be easy to update and meet the specific needs of a work area. In the VHA, a VMS displays: (1) essential information for staff members to effectively perform their work; (2) improvement project ideas; (3) current work in progress; (4) tracking of implemented improvement activities; (5) strong practices that have been effective; and (6) staff recognition for those who have enhanced patient safety, including the reporting of close calls and near misses.

The VHA uses the MESS (methods, equipment, staffing, and supplies) VMS format. This format empowers staff to identify whether proper procedures and practices are in place, essential equipment and supplies are readily available in the quantity needed, and appropriate staffing is on hand to provide safe, high-quality patient care.⁸ Colored magnets are used as visual cues in a stoplight classification system to identify low or no safety risks (green), at risk (yellow), or high risk (red). Green coded issues are addressed locally by a manager or supervisor. Yellow coded concerns require increased staff and leadership vigilance. Red coded issues indicate that patient care would be impacted that day and therefore need to be immediately escalated and addressed with senior leaders to mitigate the threat.^4,11 Dayton VAMC successfully implemented a VMS, using both physical and electronic visual management boards. The Dayton VAMC VMS boards are closely tied to tiered safety huddles and leader rounding for high reliability.   

Safety Forums

Safety forums are another foundational practice of VHA health care organizations seeking high reliability. Recurring monthly, safety forums focus on reinforcing HRO principles and practices, safety programs, the importance and appreciation of reporting, and just culture. The emphasis on just culture reminds staff that adverse events in the organization are viewed as valuable learning opportunities to understand the factors leading to the situation as opposed to immediately assigning blame.¹²

Psychological safety is another important focus. When individuals feel psychologically safe, they are more likely to voice concerns and act without fear of reprisal, which supports a culture of safety.¹³ Safety forums are open to all members of the health care organization, including both clinical and nonclinical staff. Forums can be conducted by an HRO Lead, HRO Champion, Patient Safety Manager, or even executive leadership. Rotating the responsibility of leading these forums demonstrates that high reliability and safety are everyone’s responsibility.

Safety forums publicly review and discuss errors, adverse events, close calls, and near misses. Time is also spent discussing root cause analysis trends and highlighting continuous process improvement principles and current projects. During safety forums, leaders should recognize individuals for safety behaviors and reward reporting through a safety awards program.¹⁴ All forums should conclude with a question-and-answer session. Forums typically occur in virtual 30-minute sessionsbut can last up to 60 minutes when guest speakers attend and continuing education credit is offered.

The Jesse Brown VAMC in Chicago developed an interactive monthly safety forum appealing to a broad audience. Each forum is attended by about 200 staff members and includes leader engagement and panel discussions led by the chief medical officer, with topics on both patient and team safety connecting with HRO principles. A planning committee prepares guest speakers and offers continuing education credits.

Based on the processes of high reliability industries like aviation and nuclear power, tiered safety huddles have been increasingly adopted in health care. Huddles (health care, utilizing, deliberate, discussion,linking, and events) are department-level interdisciplinary meetings that last no more than 15 minutes.¹⁵ Their purpose is to improve communication by sharing day-to-day information across multiple disciplines, identify issues that may impact the delivery of care (eg, patient and staff safety concerns, staffing issues, or inadequate supplies) and resolve problems.

Tiered safety huddles are gaining popularity, especially in organizations seeking high reliability. They are more complex than traditional huddles because of the mechanics of elevating safety issues (eg, bedside to executive leadership teams), feedback loops, and sequencing, among other factors.^15,16

Tiered safety huddles are focused, transparent forums with multidisciplinary staff, including frontline workers, along with senior leadership.^15,16 When initially implemented, tiered safety huddles may take longer than the suggested 15 minutes; however, as teams become more experienced, huddles become more efficient.¹⁵ The goal of tiered safety huddles is to proactively identify, share, address, and resolve problems that have the potential to impact the delivery of safe and quality patient care. This may include addressing staffing shortfalls, inadequate allocation of supplies and equipment, operational issues, etc.^8,15 Critical to theeffective utilization of tiered safety huddles is the appropriate escalation of issues between tiers. The most critical issues are elevated to higher tiers so they are addressed by the most qualified person in the organization.

Deciding on the number of tiers typically depends on the size and scope of services provided by the health care organization or integrated system.For example, tiered huddles in the VHA originate at the point of service (eg, critical care unit). Tier 1 includes staff members at the unit/team level along with immediate supervisors/managers. Tier 2 involves departments and service lines (eg, pharmacy, podiatry, or internal medicine) including their respective leadership. Tier 3 is the executive leadership team. This process allows for bidirectional communication instead of the traditional hierarchical communication pathway (Figure 4). Issues identified that cannot be addressed at a particular tier are elevated to the next tier. Elevated issues typically involve systems or processes requiring attention and resolution by senior leadership.¹⁵ Tier 4 huddles at the Veterans Integrated Services Network level and Tier 5 huddles at the VHA Central Office level are being initiated. These additional levels will more effectively identify system-level risks and issues that may impact multiple VHA facilities and may be addressed through centralized functions and resources.

Tiered safety huddles have been found to be instrumental to ensuring the flow of information across organizations, improving multidisciplinary and leadership engagement and collaboration, as well as increasing accountability for safety.Tiered safety huddles increase situational awareness, which improves an organization’s ability to appropriately respond to safety concerns.Furthermore, tiered safety huddles enhance teamwork and interprofessional collaboration, and have been found to significantly increase the reporting of patient safety events.^15-19

The VA Connecticut Healthcare System tiered huddles followed a pilot testing implementation process. After receiving executive-level commitment, an evidence-based process was enacted, including staff education, selecting a VMS, determining tier interaction, and deciding on metrics to track.¹⁵

Implementing Foundational Practices

To examine the progress of the implementation of the 4 foundational HRO practices, quarterly metrics derived from the OLT are reviewed to determine whether each is being implemented and sustained. The OLT also tracks progress over time. For example, at the 27 cohort 2 and lead sites that initiated leader coaching in 2021 and continued through 2022, coaches observed a 27% increase in leader rounding for high reliability and a 46% increase in the use of VMSs. For the 66 cohort 3 sites that began leader coaching in 2022, coaches documented similar changes, ranging from a 40% increase in leader rounding for high reliability to a 66% increase in the use of safety forums. Additional data continue to be collected and analyzed to publish more comprehensive findings.

DISCUSSION

Incorporating leader rounding for high reliability, VMSs, safety forums, and tiered safety huddles into daily operations is critical to building and sustaining a robust culture of safety.⁸ The 4 foundational HRO practices are instrumental in providing psychologically safe forums for staff to share concerns and actively participate. These practices also promote continual, efficient bidirectional communication throughout organizational lines and across services. The increased visibility and transparency of leaders demonstrate the importance of fostering trust, enhancing closed-loop communication with issues that arise, and building momentum to achieve high reliability. The interconnectedness of the foundational HRO practices identified and implemented by the VHA helps foster teamwork and collaboration built on trust, respect, enthusiasm for improvement, and the delivery of exceptional patient care.

CONCLUSIONS

Incorporating the 4 foundational practices into daily operations is beneficial to the delivery of safe, high-quality health care. This effective and sustained application can strengthen a health care organization on its journey to high reliability and establishing a culture of safety. To be effective, these foundational practices should be personalized to support the unique circumstances of every health care environment. While the exact methodology by which organizations implement these practices may differ, they will help organizations approach patient safety in a more transparent and thoughtful manner.

Acknowledgments

The authors thank Aaron M. Sawyer, PhD, PMP, and Jessica Fankhauser, MA, for their unwavering administrative support, and Jeff Wright for exceptional graphic design support.

Increasing complexities within health care systems are significant impediments to the consistent delivery of safe and effective patient care. These impediments include an increase in specialization of care, staff shortages, burnout, poor coordination of services and access to care, as well as rising costs.¹ High reliability organizations (HROs) provide safe, high-quality, and effective care in highly complex and risk-prone environments without causing harm or experiencing catastrophic events.²

Within the US Department of Veterans Affairs (VA), the Veterans Health Administration (VHA) operates the nation’s largest integrated health care system, providing care to > 9 million veterans. The VHA formally launched plans for an enterprise-wide HRO in February 2019. During the first year, 18 medical facilities comprised cohort1 of the journey to high reliability. Cohort 2 began in October 2020 and consisted of 54 facilities. Cohort 3 started in October 2021 with 67 facilities.³

Health care organizations seeking high reliability exercise a philosophy aimed at learning from errors and addressing system failures. High reliability is accomplished by implementing 5 principles: (1) sensitivity to operations (a heightened understanding of the current state of systems); (2) preoccupation with failure (striving to anticipate risks that might suggest a much larger system problem); (3) reluctance to simplify (avoiding making any assumptions regarding the causes of failures); (4) commitment to resilience (preparing for potential failures and bouncing back when they occur); and (5) deference to expertise (deferring to individuals with the skills and proficiency to make the best decisions).² The VHA also recognized that a successful journey to high reliability—in addition to achieving a culture of safety—relies on the implementation of foundational HRO practices: leader rounding, visual management systems, safety forums, and safety huddles. This article describes an initiative for how these foundational practices were implemented in a large integrated health care system.

BACKGROUND

The VHA has focused on 4 foundational components as part of its enterprise activities and support structure to implement HRO principles and practices. These components were selected based on pilot activities that preceded the enterprise-wide effort, reviews of the literature, and expert consultation with both government and private sector health systems. To support the implementation of these practices, the VHA provided training, toolkits, HRO executive leader coaching, and peer-to-peer mentoring. As the VHA enters its fifth year seeking high reliability, we undertook an initiative to reflect on our own experiences and refine our practices based on an updated literature review.

As part of this enterprise-wide initiative, we conducted a literature review from 2018 to March 2023 seeking recent evidence describing the value of implementing the 4 foundational HRO practices to advance high reliability and improve patient safety. A 5-year period was used to ensure recency and value of evidence.

Eligible literature was identified in PubMed, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature, ScienceDirect, Scopus, the Cochrane Library, and ProQuest Dissertations & Theses Global. Inclusion and exclusion criteria were peer-reviewed interdisciplinary documents(eg, publications, dissertations, conference proceedings, and grey literature) written in English. Search terms included high reliability organizations, foundational practices, and patient safety. Boolean operators (AND, OR) were also used in the search. The search resulted in a dearth of evidence that addressed implementation of all 4 foundational practices across a health care system. Retrieved evidence focused on the implementation of only 1 particular foundational practice in a specific health care setting. In addition to describing the formal processes for the implementation of each foundational HRO practice, a brief description of representative examples of strong practices within the VHA is provided.

To support the implementation of HROs, the VHA paired HRO executive leader coaches with select medical center directors and their leadership teams. Executive leader coaches also support an organization’s HRO Lead and HRO Champion. The HRO Lead coordinates and facilitates the implementation of HRO principles and practices in pursuit of no harm across an organization. The HRO Champion supports the same as the HRO Lead, but typically has a different specialty background. For example, if the HRO Lead has an administrative background, the HRO Champion would have a clinical background.

Coaching focuses heavily on supporting site-specific implementation and sustainment of the 4 HRO foundational practices. The aim is to accelerate change, build enduring capacity, foster a safety culture, and accelerate HRO maturity. To measure change, HRO executive leader coaches track the progress of their aligned VA medical centers (VAMCs) using the Organizational Learning Tool (OLT). This tool was developed to provide information such as a facility summary and relationships between a medical center director, HRO Lead, HRO Champion, and the executive leader coach (Figure 1). The OLT also serves as a structured process to measure leader coaching performance against mutually agreed upon objectives that ultimately contribute to enterprise outcomes. It also collects data on the progress in implementing foundational practices, strong practices, needs and gaps, and more (Figure 2). Data collected from facilities supported by HRO executive leader coaches on whether foundational practices are in place are briefly described.

Leader Rounding

Leader rounding for high reliability ensures effective, bidirectional communication and collaboration among all disciplines to improve patient safety. It is an essential feature of a robust patient safety culture and an important method for demonstrating leadership engagement with high reliability.^4,5 These rounds are conducted by organizational leadership (eg, executive teams, department/service chiefs, or unit managers) and frontline staff from different areas. They are specifically focused on high reliability, patient and staff safety, and improvement efforts. The aim is to learn about daily challenges that may contribute to patient harm.⁴

Leader rounding has been found to be highly effective at improving leadership visibility across the organization. It enhances interaction and open communication with frontline staff, fostering leader-staff collaboration and shared decision-making,as well as promoting leadership understanding of operational, clinical, nonclinical (eg, administrative, nutrition services, or facilities management), and patient/family experience issues.⁴ Collaboration among team members fosters the delivery of more effective and efficient care, increases staff satisfaction, and improves employee retention.⁶ Leader rounding for high reliability significantly contributes to the breakdown of power barriers by giving team members voice and agency, ultimately leading to deeper engagement.⁷

It is important that leader rounding for high reliability occurs as planned and when possible, scheduled in advance. This helps to avoid rounding at peak times when care activities are being performed.^4,6 When scheduling conflicts arise, another leader should be sent to participate in rounds.⁴ Developing a list of questions in advance allows leadership to prepare messaging to share with staff as it relates to high reliability and patient safety (Table).^4,6,8

Closing the loop improves bidirectional communication and is critical to leader rounding for high reliability. Closed-loop communication and following up on and/or closing out issues raised during rounding empowers the sharing of information, which is critical for advancing a culture of safety.^4,8 Enhanced feedback is also associated with greater workforce engagement, staff feeling more connected to quality improvement activities, and lower rates of employee burnout.⁷ It is important to recognize that senior leaders are not responsible for resolving all issues. If a team or manager can resolve concerns that are raised, this should be encouraged and supported. Maintaining accountability at the lowest level of the organization promotes principles and practices of high reliability (Figure 3).^4,8

The VA Bedford Healthcare System created and implemented a strong practice for leader rounding for high reliability. This phased implementation involved creating an evidence-based process, deciding on an appropriate cadence, developing a tracking tool, and measuring impact to determine the overall effectiveness of leader rounding for high reliability.⁴

A visual management system (VMS) displays clinical and operational performance aligned with HRO goals and practices. It is used to view and guide discussions between interdisciplinary teams during tiered safety huddles, leader rounds for high reliability, and frontline staff on the current status and safety trends in a particular area.^8,9 A VMS is highly effective in creating an environment where all staff members, especially frontline workers, feel empowered to voice their concerns related to safety or to identify improvement opportunities.^8,10 Increased leader engagement in patient safety and heightened transparency of information associated with the use of a VMS improves staff morale and professional satisfaction.¹⁰

A VMS may be a dry-erase or whiteboard display, paper-based display, or electronic status board.⁸ VMSs are usually located in or near work settings (eg, nurses’ station, staff break room, or conference room).⁸ Although they can take different forms and display several types of information, a VMS should be easy to update and meet the specific needs of a work area. In the VHA, a VMS displays: (1) essential information for staff members to effectively perform their work; (2) improvement project ideas; (3) current work in progress; (4) tracking of implemented improvement activities; (5) strong practices that have been effective; and (6) staff recognition for those who have enhanced patient safety, including the reporting of close calls and near misses.

The VHA uses the MESS (methods, equipment, staffing, and supplies) VMS format. This format empowers staff to identify whether proper procedures and practices are in place, essential equipment and supplies are readily available in the quantity needed, and appropriate staffing is on hand to provide safe, high-quality patient care.⁸ Colored magnets are used as visual cues in a stoplight classification system to identify low or no safety risks (green), at risk (yellow), or high risk (red). Green coded issues are addressed locally by a manager or supervisor. Yellow coded concerns require increased staff and leadership vigilance. Red coded issues indicate that patient care would be impacted that day and therefore need to be immediately escalated and addressed with senior leaders to mitigate the threat.^4,11 Dayton VAMC successfully implemented a VMS, using both physical and electronic visual management boards. The Dayton VAMC VMS boards are closely tied to tiered safety huddles and leader rounding for high reliability.   

Safety Forums

Safety forums are another foundational practice of VHA health care organizations seeking high reliability. Recurring monthly, safety forums focus on reinforcing HRO principles and practices, safety programs, the importance and appreciation of reporting, and just culture. The emphasis on just culture reminds staff that adverse events in the organization are viewed as valuable learning opportunities to understand the factors leading to the situation as opposed to immediately assigning blame.¹²

Psychological safety is another important focus. When individuals feel psychologically safe, they are more likely to voice concerns and act without fear of reprisal, which supports a culture of safety.¹³ Safety forums are open to all members of the health care organization, including both clinical and nonclinical staff. Forums can be conducted by an HRO Lead, HRO Champion, Patient Safety Manager, or even executive leadership. Rotating the responsibility of leading these forums demonstrates that high reliability and safety are everyone’s responsibility.

Safety forums publicly review and discuss errors, adverse events, close calls, and near misses. Time is also spent discussing root cause analysis trends and highlighting continuous process improvement principles and current projects. During safety forums, leaders should recognize individuals for safety behaviors and reward reporting through a safety awards program.¹⁴ All forums should conclude with a question-and-answer session. Forums typically occur in virtual 30-minute sessionsbut can last up to 60 minutes when guest speakers attend and continuing education credit is offered.

The Jesse Brown VAMC in Chicago developed an interactive monthly safety forum appealing to a broad audience. Each forum is attended by about 200 staff members and includes leader engagement and panel discussions led by the chief medical officer, with topics on both patient and team safety connecting with HRO principles. A planning committee prepares guest speakers and offers continuing education credits.

Based on the processes of high reliability industries like aviation and nuclear power, tiered safety huddles have been increasingly adopted in health care. Huddles (health care, utilizing, deliberate, discussion,linking, and events) are department-level interdisciplinary meetings that last no more than 15 minutes.¹⁵ Their purpose is to improve communication by sharing day-to-day information across multiple disciplines, identify issues that may impact the delivery of care (eg, patient and staff safety concerns, staffing issues, or inadequate supplies) and resolve problems.

Tiered safety huddles are gaining popularity, especially in organizations seeking high reliability. They are more complex than traditional huddles because of the mechanics of elevating safety issues (eg, bedside to executive leadership teams), feedback loops, and sequencing, among other factors.^15,16

Tiered safety huddles are focused, transparent forums with multidisciplinary staff, including frontline workers, along with senior leadership.^15,16 When initially implemented, tiered safety huddles may take longer than the suggested 15 minutes; however, as teams become more experienced, huddles become more efficient.¹⁵ The goal of tiered safety huddles is to proactively identify, share, address, and resolve problems that have the potential to impact the delivery of safe and quality patient care. This may include addressing staffing shortfalls, inadequate allocation of supplies and equipment, operational issues, etc.^8,15 Critical to theeffective utilization of tiered safety huddles is the appropriate escalation of issues between tiers. The most critical issues are elevated to higher tiers so they are addressed by the most qualified person in the organization.

Deciding on the number of tiers typically depends on the size and scope of services provided by the health care organization or integrated system.For example, tiered huddles in the VHA originate at the point of service (eg, critical care unit). Tier 1 includes staff members at the unit/team level along with immediate supervisors/managers. Tier 2 involves departments and service lines (eg, pharmacy, podiatry, or internal medicine) including their respective leadership. Tier 3 is the executive leadership team. This process allows for bidirectional communication instead of the traditional hierarchical communication pathway (Figure 4). Issues identified that cannot be addressed at a particular tier are elevated to the next tier. Elevated issues typically involve systems or processes requiring attention and resolution by senior leadership.¹⁵ Tier 4 huddles at the Veterans Integrated Services Network level and Tier 5 huddles at the VHA Central Office level are being initiated. These additional levels will more effectively identify system-level risks and issues that may impact multiple VHA facilities and may be addressed through centralized functions and resources.

Tiered safety huddles have been found to be instrumental to ensuring the flow of information across organizations, improving multidisciplinary and leadership engagement and collaboration, as well as increasing accountability for safety.Tiered safety huddles increase situational awareness, which improves an organization’s ability to appropriately respond to safety concerns.Furthermore, tiered safety huddles enhance teamwork and interprofessional collaboration, and have been found to significantly increase the reporting of patient safety events.^15-19

The VA Connecticut Healthcare System tiered huddles followed a pilot testing implementation process. After receiving executive-level commitment, an evidence-based process was enacted, including staff education, selecting a VMS, determining tier interaction, and deciding on metrics to track.¹⁵

Implementing Foundational Practices

To examine the progress of the implementation of the 4 foundational HRO practices, quarterly metrics derived from the OLT are reviewed to determine whether each is being implemented and sustained. The OLT also tracks progress over time. For example, at the 27 cohort 2 and lead sites that initiated leader coaching in 2021 and continued through 2022, coaches observed a 27% increase in leader rounding for high reliability and a 46% increase in the use of VMSs. For the 66 cohort 3 sites that began leader coaching in 2022, coaches documented similar changes, ranging from a 40% increase in leader rounding for high reliability to a 66% increase in the use of safety forums. Additional data continue to be collected and analyzed to publish more comprehensive findings.

DISCUSSION

Incorporating leader rounding for high reliability, VMSs, safety forums, and tiered safety huddles into daily operations is critical to building and sustaining a robust culture of safety.⁸ The 4 foundational HRO practices are instrumental in providing psychologically safe forums for staff to share concerns and actively participate. These practices also promote continual, efficient bidirectional communication throughout organizational lines and across services. The increased visibility and transparency of leaders demonstrate the importance of fostering trust, enhancing closed-loop communication with issues that arise, and building momentum to achieve high reliability. The interconnectedness of the foundational HRO practices identified and implemented by the VHA helps foster teamwork and collaboration built on trust, respect, enthusiasm for improvement, and the delivery of exceptional patient care.

CONCLUSIONS

Incorporating the 4 foundational practices into daily operations is beneficial to the delivery of safe, high-quality health care. This effective and sustained application can strengthen a health care organization on its journey to high reliability and establishing a culture of safety. To be effective, these foundational practices should be personalized to support the unique circumstances of every health care environment. While the exact methodology by which organizations implement these practices may differ, they will help organizations approach patient safety in a more transparent and thoughtful manner.

Acknowledgments

The authors thank Aaron M. Sawyer, PhD, PMP, and Jessica Fankhauser, MA, for their unwavering administrative support, and Jeff Wright for exceptional graphic design support.

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

Perioperative visual loss (POVL) is a well-documented yet uncommon complication of nonocular surgery. Patients undergoing cardiac and spinal surgery are at the greatest risk, though POVL may occur during other neurosurgical and vascular procedures as well. The most common causes of POVL are central retinal artery occlusion (CRAO) and ischemic optic neuropathy (ION),^1-3 though cases of orbital compartment syndrome (OCS) have also been reported.^4-7

We describe a case of POVL during a temporal meningioma excision using the pterional approach. Though the etiology is not fully understood, the patient’s clinical course was complicated by a third cranial nerve (CN III) palsy and CRAO, which, together with the patient’s presentation, were consistent with previously documented cases of OCS. The goals of this case report are to increase awareness of this surgical outcome, identify practices that may have contributed to its development, and delineate methods to minimize its occurrence.

Informed consent regarding this research was obtained from the patient and an institutional Health Insurance Portability and Accountability Act authorization form was completed. This manuscript adheres to the applicable Enhancing the Quality and Transparency of Health Research guideline.⁸

Case Presentation

A 47-year-old woman underwent a left temporal craniotomy for resection of a sphenoid wing meningioma discovered during a workup for persistent headaches. She had no medical history of diabetes, hypertension, coronary artery disease, or ophthalmic disease. Two months before her scheduled surgery, the patient reported bilateral blurry vision and underwent ophthalmologic evaluation. Her intraocular pressure (IOP) was normal, and she had no pupillary or retinal disease. She showed evidence of decreased vision in her left eye, suggesting a possible mass effect from her meningioma. Subsequent imaging of the optic nerve and retina had unremarkable physiology (Figure 1). Preoperative magnetic resonance imaging (MRI) demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus(Figure 2). There was a superior mass effect on the left middle cerebral artery, but all vessels were patent without evidence of thrombosis.

The patient underwent general anesthesia with invasive hemodynamic monitoring used throughout the procedure. She was induced with fentanyl, propofol, and rocuronium; anesthesia was maintained with isoflurane and a remifentanil infusion. Hypotension was treated with phenylephrine and intravenous fluids. Intraoperative neuromonitoring with electroencephalogram (EEG) and somatosensory evoked potentials was performed. During the surgery, the patient was positioned supine in a Mayfield 3-point head fixation system. All pressure points were padded appropriately and continually checked. A standard left pterional craniotomy was performed, and the scalp was reflected anteriorly and secured using fish hooks with rubber bands. The operation did not violate the cavernous sinus or orbital compartment. There was no evidence of active bleeding upon inspection nor with the Valsalva maneuver. No changes were noted in EEG or somatosensory evoked potentials; blood pressure remained within 20 mm Hg of the patient’s baseline. She was extubated at the end of the 10-hour case and was hemodynamically stable upon transport to the surgical intensive care unit. Postoperative imaging confirmed the successful removal of the left sphenoid wing meningioma.

The patient’s postoperative examination demonstrated a 5 mm dilated, nonresponsive left pupil, though the patient did not report visual loss at that time. Defects were noted in the inferior oblique, superior, inferior, and medial rectus muscles, consistent with CN III palsy. The surgery included manipulation of CN III, which made this a possible outcome, but an alternate causative pathology like OCS was not immediately suspected. Postoperative computed tomography (CT) showed an expected pneumocephalus and left scalp swelling without evidence of mass effect or midline shift.

Repeat MRI showed denervation of the left medial rectus and minimal left-sided proptosis. A 3-month ophthalmologic follow-up revealed a persistent CN III palsy, including an afferent pupillary defect, absence of light perception in her left eye, and continued ophthalmoplegia. Repeat examination showed a left-sided 4+ afferent pupillary defect unreactive to light, 4+ pallor surrounding the optic nerve, macular atrophy, sclerotic vessels, and 17 mm Hg intraocular pressure bilaterally. The eye had diffuse atrophy of the inner retina and significant patchy atrophy of the outer retinal components without neovascularization of the iris. Postoperative retinal imaging can be seen in Figure 3. Her vision loss persisted at this encounter and has continued through subsequent follow-up examinations.

Discussion

Perioperative visual loss is a rare surgical complication, with an estimated incidence of once in every 60,000 to 125,000 cases.⁹ The mechanism of injury is variable and dependent upon the type of surgical intervention, with cardiac and spine surgeries carrying the greatest risk.^10,11 The injury often results in either CRAO or ION, which may result in visual loss.^1-3 POVL can also occur in the aftermath of rapid changes in intracranial pressure during decompressive craniotomies, though the pathophysiology in such cases is not well understood.⁵

Among the myriad ways in which POVL can occur, neurosurgical cases carry the unique risk of direct cranial nerve injury. Such an insult can lead to vision loss via optic nerve damage or ophthalmoplegia if damage occurs to CN III, IV, or VI. This can occur during manipulation or resection, especially if the surgical approach involves the orbital cavity or the cavernous sinus. Though neither space was entered in this patient, direct injury cannot be ruled out as the etiology for either her vision loss or persistent ophthalmoplegia. An alternate causative scenario for both symptoms involve an impaired blood supply, with the vision loss potentially occurring secondary to CRAO and the ophthalmoplegia to an alternate cause of decreased blood flow. It is unclear which of these 2 conditions occurred first or if they occurred due to the same insult, but OCS could lead to both. Though it is a less common etiology for POVL, this patient’s presentation was similar to those in previously reported cases, and OCS was identified as the likely diagnosis.

OCS is precipitated by an elevated orbital pressure, which leads to ischemia of the retina and damage to orbital contents. Though associated with retrobulbar hemorrhage and orbital trauma, another proposed mechanism for OCS is extrinsic orbital compression, resulting in increased IOP and subsequent CRAO.¹⁰ A cherry red spot is visible on fundoscopy, as only the macula with its thin retinal layer will permit the choroidal vessels to be visualized. In a separate process, the relative increase in orbital pressure may lead to impaired perfusion or damage of CN III. However, a causative relationship between the 2 may be difficult to establish. Such an injury to the oculomotor nerve is demonstrated by impaired function of the inferior oblique, superior rectus, inferior rectus, and medial rectus muscles, which may persist even after the compressive symptoms of OCS have resolved.¹² Other reported symptoms of OCS include erythema, ophthalmoplegia, conjunctival chemosis, ptosis, corneal abrasion, and eyelid edema.^12-15

Alternate Diagnoses

OCS is a diagnosis of exclusion, and several alternate mechanisms were considered before identifying it as the likely etiology. The patient’s preoperative imaging demonstrated a stable enhancing mass involving the left great sphenoid wing and left cavernous sinus, with displacement of the left middle cerebral artery, left cavernous internal carotid artery, and left optic canal. Dissection and removal of this tumor could have compromised the arterial or venous blood supply to the orbit, thus causing ischemia to the retina and other ocular structures. CN III was manipulated during surgery, and it may have been inadvertently damaged during exposure or resection of the tumor.

The patient’s Valsalva-dependent patent foramen ovale put her at risk of a paroxysmal embolus as an alternate explanation, particularly as a Valsalva maneuver was utilized to confirm hemostasis. The patient did not, however, demonstrate any evidence of venous thromboembolism (VTE) on ultrasound, nor did she have the common risk factors of hypertension, diabetes, or smoking history that would increase VTE risk.¹⁶Her cancer diagnosis and surgical status may have put her at risk of VTE, but she did not have any clinical or laboratory values suggestive of hypercoagulability. Had an embolism occurred, it may have compromised the orbital blood supply and led to the CRAO. A similar scenario may have occurred from an atherosclerotic plaque in either of her carotid arteries, as she did have evidence of atherosclerosis on postoperative CT angiography. However, atherosclerosis as a risk factor for POVL appears to be related more to its impact upon impaired blood supply rather than as an embolic source. The patient did not have any significant intraoperative hypotensive episodes, making ION in the setting of atherosclerosis and hypotension a less likely etiology.¹⁷

This patient differed from other reported OCS cases. She was never placed in a prone or jackknife position, nor was she agitated or straining for a sustained period. These factors, along with the fact that the orbital compartment was not entered, decreased the likelihood of intraorbital hemorrhage and other intrinsic causes of elevated IOP.¹² Additionally, the presentation of our patient’s vision loss was delayed compared with other cases, despite clinicians observing a dilated left pupil and CN III palsy on examination immediately after surgery.¹⁴ It is significant to note that OCS may not demonstrate a significant increase in IOP once the source of compression is removed, which may explain the absence of proptosis on her postoperative examination.

The diagnosis of OCS was primarily implicated by the positioning of the myocutaneous flap during the pterional approach to craniotomy. It was retracted anteriorly and superiorly, ultimately resting over her left orbit for most of the 10-hour surgery. Kim and colleagues found that myocutaneous flaps may increase IOP as much as 17.5 mm Hg if improperly positioned, providing an unrecognized source of compression and increasing the risk of damage to orbital contents. According to their review, elevated IOP > 40 mm Hg, particularly over several hours, can compromise blood flow to the optic nerve and increase the risk for POVL.¹⁸ The flap was secured using fish hooks and rubber bands. However, it is suspected that the orbital rim did not fully support its pressure, thereby resting to some degree directly on the globe for an extended period and compromising the orbital blood supply. There are no current methods for measuring intraoperative IOP, though surrogate markers are under investigation and may yield clinical utility.¹⁸ The myocutaneous flap was created and positioned by the surgeons, but it may be that increased vigilance and communication from the anesthesia and nursing teams could have prevented it from remaining in an improper position.

Conclusions

Despite having few reported cases, OCS must be considered in neurosurgical patients with ophthalmoplegia and CRAO on postoperative examinations. Myocutaneous flaps that are retracted across the orbit can lead to significant elevations in IOP, leading to vision loss, which likely occurred with the patient in this case. Though protecting neurovascular structures is within the purview of the surgeon, all members of the intraoperative team should assist with ensuring proper flap positioning. These measures can help ensure adequate blood flow to the ophthalmic artery, decrease the likelihood of elevated IOP due to extrinsic compression, and help prevent the development of POVL and OCS in these patients.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.

The Centers for Disease Control and Prevention (CDC) classifies individuals with a body mass index (BMI) of 25 to 29.9as overweight and those with a BMI > 30 as obese (obesity classes: I, BMI 30 to 34.9; II, BMI 35 to 39.9; and III, BMI ≥ 40).¹ In 2011, the CDC estimated that 27.4% of adults in the United States were obese; less than a decade later, that number increased to 31.9%.¹ In that same period, the percentage of adults in Indiana classified as obese increased from 30.8% to 36.8%.¹ About 1 in 14 individuals in the US have class III obesity and 86% of veterans are either overweight or obese.²

High medical expenses can likely be attributed to the long-term health consequences of obesity. Compared to those with a healthy weight, individuals who are overweight or obese are at an increased risk for high blood pressure, high low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, high triglyceride levels, type 2 diabetes mellitus (T2DM), coronary heart disease, stroke, gallbladder disease, osteoarthritis, sleep apnea, cancer, mental health disorders, body pain, low quality of life, and death.³ Many of these conditions lead to increased health care needs, medication needs, hospitalizations, and overall health care system use.

Guidelines for the prevention and treatment of obesity have been produced by the American Heart Association, American College of Cardiology, and The Obesity Society; the Endocrine Society; the American Diabetes Association; and the US Departments of Veterans Affairs (VA) and Defense. Each follows a general algorithm to manage and prevent adverse effects (AEs) related to obesity. General practice is to assess a patient for elevated BMI (> 25), implement intense lifestyle modifications including calorie restriction and exercise, reassess for a maintained 5% to 10% weight loss for cardiovascular benefits, and potentially assess for pharmacological or surgical intervention to assist in weight loss.^2,4-6

While some weight loss medications (eg, phentermine/topiramate, naltrexone/bupropion, orlistat, and lorcaserin) tend to have unfavorable AEs or mixed efficacy, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have provided new options.^7-10 Lorcaserin, for example, was removed from the market in 2020 due to its association with cancer risks.¹¹ The GLP-1RAs liraglutide and semaglutide received US Food and Drug Administration (FDA) approval for weight loss in 2014 and 2021, respectively.^12,13 GLP-1RAs have shown the greatest efficacy and benefits in reducing hemoglobin A_1c (HbA_1c); they are the preferred agents for patients who qualify for pharmacologic intervention for weight loss, especially those with T2DM. However, these studies have not evaluated the long-term outcomes of using these medications for weight loss and may not reflect the veteran population.^14,15

At Veteran Health Indiana (VHI), clinicians may use several weight loss medications for patients to achieve 5% to 10% weight loss. The medications most often used include liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone. However, more research is needed to determine which weight loss medication is the most beneficial for veterans, particularly following FDA approval of GLP-1RAs. At VHI, phentermine/topiramate is the preferred first-line agent unless patients have contraindications for use, in which case naltrexone/bupropion is recommended. These are considered first-line due to their ease of use in pill form, lower cost, and comparable weight loss to the GLP-1 medication class.² However, for patients with prediabetes, T2DM, BMI > 40, or BMI > 35 with specific comorbid conditions, liraglutide is preferred because of its beneficial effects for both weight loss and blood glucose control.²

This study aimed to expand on the 2021 Hood and colleagues study that examined total weight loss and weight loss as a percentage of baseline weight in patients with obesity at 3, 6, 12, and > 12 months of pharmacologic therapy by extending the time frame to 48 months.¹⁶ This study excluded semaglutide because few patients were prescribed the medication for weight loss during the study.

METHODS

We conducted a single-center, retrospective chart review of patients prescribed weight loss medications at VHI. A patient list was generated based on prescription fills from June 1, 2017, to July 31, 2021. Data were obtained from the Computerized Patient Record System; patients were not contacted. This study was approved by the Indiana University Health Institutional Review Board and VHI Research and Development Committee.

At the time of this study, liraglutide, phentermine/topiramate, naltrexone/bupropion, orlistat, and phentermine alone were available at VHI for patients who met the clinical criteria for use. All patients must have been enrolled in dietary and lifestyle management programs, including the VA MOVE! program, to be approved for these medications. After the MOVE! orientation, patients could participate in group or individual 12-week programs that included weigh-ins, goal-setting strategies, meal planning, and habit modification support. If patients could not meet in person, phone and other telehealth opportunities were available.

Patients were included in the study if they were aged ≥ 18 years, received a prescription for any of the 5 available medications for weight loss during the enrollment period, and were on the medication for ≥ 6 consecutive months. Patients were excluded if they received a prescription, were treated outside the VA system, or were pregnant. The primary indication for the included medication was not weight loss; the primary indication for the GLP-1RA was T2DM, or the weight loss was attributed to another disease. Adherence was not a measured outcome of this study; if patients were filling the medication, it was assumed they were taking it. Data were collected for each instance of medication use; as a result, a few patients were included more than once. Data collection for a failed medication ended when failure was documented. New data points began when new medication was prescribed; all data were per medication, not per patient. This allowed us to account for medication failure and provide accurate weight loss results based on medication choice within VHI.

Primary outcomes included total weight loss and weight loss as a percentage ofbaseline weight during the study period at 3, 6, 12, 24, 36, and 48 months of therapy. Secondary outcomes included the percentage of patients who lost 5% to 10% of their body weight from baseline; the percentage of patients who maintained ≥ 5% weight loss from baseline to 12, 24, 36, and 48 months if maintained on medication for that duration; duration of medication treatment in weeks; medication discontinuation rate; reason for medication discontinuation; enrollment in the MOVE! clinic and the time enrolled; percentage of patients with a BMI of 18 to 24.9 at the end of the study; and change in HbA_1c at 3, 6, 12, 24, 36, and 48 months.

Demographic data included race, age, sex, baseline weight, height, baseline BMI, and comorbid conditions (collected based on the most recent primary care clinical note before initiating medication). Medication data collected included medications used to manage comorbidities. Data related to weight management medication included prescribing clinic, maintenance dose of medication, duration of medication during the study period, the reason for medication discontinuation, or bariatric surgery intervention if applicable.

Basic descriptive statistics were used to characterize study participants. For continuous data, analysis of variance tests were used; if those results were not normal, then nonparametric tests were used, followed by pairwise tests between medication groups if the overall test was significant using the Fisher significant differences test. For nominal data, χ² or Fisher exact tests were used. For comparisons of primary and secondary outcomes, if the analyses needed to include adjustment for confounding variables, analysis of covariance was used for continuous data. A 2-sided 5% significance level was used for all tests.

RESULTS

A total of 228 instances of medication use were identified based on prescription fills; 123 did not meet inclusion criteria (117 for < 6 consecutive months of medication use) (Figure). The study included 105 participants with a mean age of 56 years; 80 were male (76.2%), and 85 identified as White race (81.0%). Mean (SD) weight was 130.1 kg (26.8) and BMI was 41.6 (7.2). The most common comorbid disease states among patients included hypertension, dyslipidemia, obstructive sleep apnea, and T2DM (Table 1). The baseline characteristics were comparable to those of Hood and colleagues.¹⁶

Most patients at VHI started on liraglutide (63%) or phentermine/topiramate (28%). For primary and secondary outcomes, statistics were calculated to determine whether the results were statistically significant for comparing the liraglutide and phentermine/topiramate subgroups. Sample sizes were too small for statistical analysis for bupropion/naltrexone, phentermine, and orlistat.

Primary Outcomes

The mean (SD) weight of participants dropped 8.1% from 130.1 kg to 119.5 kg over the patient-specific duration of weight management medication therapy for an absolute difference of 10.6 kg (9.7). Duration of individual medication use varied from 6 to 48 months. Weight loss was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. Patient weight was not recorded after the medication was discontinued.

When classified by medication choice, the mean change in weight over the duration of the study was −23.9 kg for 2 patients using orlistat, −10.2 kg for 46 patients using liraglutide, −11.0 kg for 25 patients using phentermine/topiramate, -7.4 kg for 1 patient using phentermine, and -13.0 kg for 4 patients using naltrexone/bupropion. Patients without a weight documented at the end of their therapy or at the conclusion of the data collection period were not included in the total weight loss at the end of therapy. There were 78 documented instances of weight loss at the end of therapy (Table 2).

Body weight loss percentage was recorded at 6, 12, 24, 36, and 48 months of weight management therapy. The mean (SD) body weight loss percentage over the duration of the study was 9.2% (11.2). When classified by medication choice, the mean percentage of body weight loss was 16.8% for 2 patients using orlistat, 9.4% for 46 patients using liraglutide, 8.2% for 25 patients using phentermine/topiramate, 6.0% for 1 patient using phentermine alone, and 10.6% for 4 patients using naltrexone/bupropion (Table 3).

Secondary Outcomes

While none of the secondary outcomes were statistically significant, the results of this study suggest that both medications may contribute to weight loss in many patients included in this study. Almost two-thirds of the included patients analyzed lost ≥ 5% of weight from baseline while taking weight management medication. Sixty-six patients (63%) lost ≥ 5% of body weight at any time during the data collection period. When stratified by liraglutide and phentermine/topiramate, 41 patients (63%) taking liraglutide and 20 patients (67%) taking phentermine/topiramate lost ≥ 5% of weight from baseline. Of the 66 patients who lost ≥ 5% of body weight from baseline, 36 (55%) lost ≥ 10% of body weight from baseline at any time during the data collection period.

The mean (SD) duration for weight management medication use was 23 months (14.9). Phentermine/topiramate was tolerated longer than liraglutide: 22.7 months vs 21.7 months, respectively (Table 4).

The average overall documented medication discontinuation rate was 35.2%. Reasons for discontinuation included 21 patient-elected discontinuations, 8 patients no longer met criteria for use, 4 medications were no longer indicated, and 4 patients experienced AEs. It is unknown whether weight management medication was discontinued or not in 18 patients (17.2%).

This study evaluated the use and outcomes of weight loss medications over a longer period (up to 48 months) than what was previously studied among patients at VHI (12 months). The study aimed to better understand the long-term effect of weight loss medications, determine which medication had better long-term outcomes, and examine the reasons for medication discontinuation.

The results of this study displayed some similarities and differences compared with the Hood and colleagues study.¹⁶ Both yielded similar results for 5% of body weight loss and 10% of body weight loss. The largest difference was mean weight loss over the study period. In this study, patients lost a mean 10.6 kg over the course of weight loss medication use compared to 15.8 kg found by Hood and colleagues.¹⁶ A reason patients in the current study lost less weight overall could be the difference in time frames. The current study encompassed the COVID-19 pandemic, meaning fewer overall in-person patient appointments, which led to patients being lost to follow-up, missing weigh-ins during the time period, and gaps in care. For some patients, the pandemic possibly contributed to depression, missed medication doses, and a more sedentary lifestyle, leading to more weight gain.¹⁷ Telemedicine services at VHI expanded during the pandemic in an attempt to increase patient monitoring and counseling. It is unclear whether this expansion was enough to replace the in-person contact necessary to promote a healthy lifestyle.

VA pharmacists now care for patients through telehealth and are more involved in weight loss management. Since the conclusion of the Hood and colleagues study and start of this research, 2 pharmacists at VHI have been assigned to follow patients for obesity management to help with adherence to medication and lifestyle changes, management of AEs, dispense logistics, interventions for medications that may cause weight gain, and case management of glycemic control and weight loss with GLP-1RAs. Care management by pharmacists at VHI helps improve the logistics of titratable orders and save money by improving the use of high-cost items like GLP-1RAs. VA clinical pharmacy practitioners already monitor GLP-1RAs for patients with T2DM, so they are prepared to educate and assist patients with these medications.

It is important to continue developing a standardized process for weight loss medication management across the VA to improve the quality of patient care and optimize prescription outcomes. VA facilities differ in how weight loss management care is delivered and the level at which pharmacists are involved. Given the high rate of obesity among patients at the VA, the advent of new prescription options for weight loss, and the high cost associated with these medications, there has been increased attention to obesity care. Some Veterans Integrated Service Networks are forming a weight management community of practice groups to create standard operating procedures and algorithms to standardize care. Developing consistent processes is necessary to improve weight loss and patient care for veterans regardless where they receive treatment.

Limitations

The data used in this study were dependent on clinician documentation. Because of a lack of documentation in many instances, it was difficult to determine the full efficacy of the medications studied due to missing weight recordings. The lack of documentation made it difficult to determine whether patients were enrolled and active in the MOVE! program. It is required that patients enroll in MOVE! to obtain medications, but many did not have any follow-up MOVE! visits after initially obtaining their weight loss medication.

In this study, differences in the outcomes of patients with and without T2DM were not compared. It is the VA standard of care to prefer liraglutide over phentermine/topiramate in patients with T2DM or prediabetes.² This makes it difficult to assess whether phentermine/topiramate or liraglutide is more effective for weight loss in patients with T2DM. Weight gain after the discontinuation of weight loss medications was not assessed. Collecting this data may help determine whether a certain weight loss medication is less likely to cause rebound weight gain when discontinued.

Other limitations to this study consisted of excluding patients who discontinued therapy within 6 months, small sample sizes on some medications, and lack of data on adherence. Adherence was based on medication refills, which means that if a patient refilled the medication, it was assumed they were taking it. This is not always the case, and while accurate data on adherence is difficult to gather, it can impact how results may be interpreted. These additional limitations make it difficult to accurately determine the efficacy of the medications in this study.

CONCLUSIONS

This study found similar outcomes to what has been observed in larger clinical trials regarding weight loss medications. Nevertheless, there was a lack of accurate clinical documentation for most patients, which limits the conclusions. This lack of documentation potentially led to inaccurate results. It revealed that many patients at VHI did not uniformly receive consistent follow-up after starting a weight loss medication during the study period. With more standardized processes implemented at VA facilities, increased pharmacist involvement in weight loss medication management, and increased use of established telehealth services, patients could have the opportunity for closer follow-up that may lead to better weight loss outcomes. With these changes, there is more reason for additional studies to be conducted to assess follow-up, medication management, and weight loss overall.