Listen to Stephen Jencks, MD, MPH, discuss why the issue of hospital readmissions has caught the attention of doctors and professional societies.

Listen to veteran hospitalist Bradley Sherman, MD, FHM, chairman of the Department of Medicine at Glen Cove Hospital, part of the North Shore/LIJ Health System in New York, talk about what you can do both now and over the next year to help your institutions decrease readmission rates.

Listen to Stephen Jencks, MD, MPH, discuss why the issue of hospital readmissions has caught the attention of doctors and professional societies.

Listen to veteran hospitalist Bradley Sherman, MD, FHM, chairman of the Department of Medicine at Glen Cove Hospital, part of the North Shore/LIJ Health System in New York, talk about what you can do both now and over the next year to help your institutions decrease readmission rates.

Listen to Stephen Jencks, MD, MPH, discuss why the issue of hospital readmissions has caught the attention of doctors and professional societies.

Listen to veteran hospitalist Bradley Sherman, MD, FHM, chairman of the Department of Medicine at Glen Cove Hospital, part of the North Shore/LIJ Health System in New York, talk about what you can do both now and over the next year to help your institutions decrease readmission rates.

Which patients are you most likely to see again? It’s a particularly vexing question for hospitalists amid the heightened focus on lowering hospital readmissions, and one that several recent studies have sought to address.

One Journal of Hospital Medicine analysis of more than 10,300 admissions found that unplanned rehospitalizations within 30 days of discharge were far more likely for African-American patients and those on high-risk medications like narcotics and corticosteroids.¹ Patients with such chronic conditions as cancer, renal failure, and congestive heart failure also were at increased risk.

A second, smaller study of 142 inpatients who had been hospitalized within the preceding six months found that chronic disease, depression, and being underweight or obese all predicted a higher risk of another readmission within the next six months.²

And a third report in the Journal of Urban Health examined more than 36,000 Medicare patients admitted to urban public hospitals to assess which were most likely to return within the following year. Chronic medical conditions, substance abuse, and homelessness all contributed to increased odds.³

Whenever there is a program that has financial incentives, people always get concerned that they have patients who are somehow different. Inherent in that assumption is: more difficult to manage or sicker or more complicated.—Lakshmi Halasyamani, MD, SFHM, SHM board member, vice president for medical affairs, Saint Joseph Mercy Health System, Ann Arbor, Mich.

Most efforts aimed at reducing rehospitalizations, such as SHM’s Project BOOST, include a risk assessment that can point to potential trouble spots for individual patients. For certain populations, research has highlighted socioeconomic and racial disparities in access to healthcare that likely lead to unnecessary hospitalizations. But it’s one thing to identify the factors associated with higher rates, and quite another to actively manage them, especially when many crop up well beyond a hospital’s walls. Anxiety over these contributing factors is steadily building in anticipation of Medicare penalties for excessively high readmission rates set to begin in 2012.

“Whenever there is a program that has financial incentives, people always get concerned that they have patients who are somehow different,” says Lakshmi Halasyamani, MD, SFHM, SHM board member and vice president for medical affairs at Saint Joseph Mercy Health System in Ann Arbor, Mich. “Inherent in that assumption is: more difficult to manage or sicker or more complicated.”

Stephen Jencks, MD, MPH, an independent healthcare safety and quality consultant based in Baltimore, says he’s heard the same complaint for three decades. “It’s what we call the 'Lake Wobegon effect': All of our patients are sicker than average.

“I think it’s just a really poor way to go about what is a very human sort of question,” he adds. “If Mrs. Jones is back in the hospital because she didn’t understand the discharge instructions, the question is not ‘Does my population have more literacy problems than somebody else’s population of patients?’ The question is ‘What can we do for Mrs. Jones so she can understand this stuff?’ ” (For help communicating with patients, check out SHM's on-demand webinar, "Implementing Teach Back as a System-Wide Patient Communication Strategy.")

Healthcare experts say it’s not difficult to find challenges unique to particular urban areas or populations. Florida Hospital Association President Bruce Rueben, MBA, says many Floridians speak English as a second language, making clear communication critical. The state also has one of the highest percentages of elderly residents and is in a funding crisis that has required providers to do more with less. But instead of worrying about exceptions or anomalies, Rueben says, focusing on the best overall readmission-reducing approaches will help ensure that all patients are being treated and discharged effectively.

What about dealing with specific conditions? Paul McGann, MD, deputy chief medical officer at the Centers for Medicare & Medicaid Services (CMS), says good evidence exists for the effectiveness of interventions aimed at diseases ranging from congestive heart failure and cancer to chronic obstructive lung disease, ulcers, and stroke. But data from Medicare’s Care Transitions Program, he says, suggest that even if all hospitals pursued the dozens of disease-specific interventions collectively implemented by the program’s participants, they still wouldn’t address more than about half of the causes of readmission. Based on that finding, he says, project leaders have insisted on an all-cause focus.

Dr. Halasyamani says it’s only natural to sometimes focus on the exception rather than the rule. “And we’ve all had those experiences where, boy, you feel like you’ve done everything you can and the patient still comes back,” she says. “But having said that, we also have opportunities where we haven’t done everything that we can and the patient comes back. So I think we need to focus on that first, rather than say, ‘Well, this isn’t fixable based on all of the patient-level issues.’”

Rachel George, MD, MBA, FHM, regional medical director and vice president of operations for West Cogent Healthcare Inc., says it all comes down to perspective. “Instead of looking at what’s the percentage that we can’t deal with,” she says, “let’s look at the patient population that we can affect.”

Bryn Nelson is a freelance medical writer based in Seattle.

References

1. Allaudeen N, Vidyarthi A, Maselli J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60.

2. Mudge AM, Kasper KM, Clair, A, et al. Recurrent readmissions in medical patients: a prospective study. J Hosp Med. 2011;6(2):61-67.

3. Raven, MC, Billings, JC, Goldfrank LR, Manheimer ED, Gourevitch MN. Medicaid patients at high risk for frequent hospital admission: real-time identification and remediable risks. J Urb Health. 2009;86(2):230-241.

Which patients are you most likely to see again? It’s a particularly vexing question for hospitalists amid the heightened focus on lowering hospital readmissions, and one that several recent studies have sought to address.

One Journal of Hospital Medicine analysis of more than 10,300 admissions found that unplanned rehospitalizations within 30 days of discharge were far more likely for African-American patients and those on high-risk medications like narcotics and corticosteroids.¹ Patients with such chronic conditions as cancer, renal failure, and congestive heart failure also were at increased risk.

A second, smaller study of 142 inpatients who had been hospitalized within the preceding six months found that chronic disease, depression, and being underweight or obese all predicted a higher risk of another readmission within the next six months.²

And a third report in the Journal of Urban Health examined more than 36,000 Medicare patients admitted to urban public hospitals to assess which were most likely to return within the following year. Chronic medical conditions, substance abuse, and homelessness all contributed to increased odds.³

Whenever there is a program that has financial incentives, people always get concerned that they have patients who are somehow different. Inherent in that assumption is: more difficult to manage or sicker or more complicated.—Lakshmi Halasyamani, MD, SFHM, SHM board member, vice president for medical affairs, Saint Joseph Mercy Health System, Ann Arbor, Mich.

Most efforts aimed at reducing rehospitalizations, such as SHM’s Project BOOST, include a risk assessment that can point to potential trouble spots for individual patients. For certain populations, research has highlighted socioeconomic and racial disparities in access to healthcare that likely lead to unnecessary hospitalizations. But it’s one thing to identify the factors associated with higher rates, and quite another to actively manage them, especially when many crop up well beyond a hospital’s walls. Anxiety over these contributing factors is steadily building in anticipation of Medicare penalties for excessively high readmission rates set to begin in 2012.

“Whenever there is a program that has financial incentives, people always get concerned that they have patients who are somehow different,” says Lakshmi Halasyamani, MD, SFHM, SHM board member and vice president for medical affairs at Saint Joseph Mercy Health System in Ann Arbor, Mich. “Inherent in that assumption is: more difficult to manage or sicker or more complicated.”

Stephen Jencks, MD, MPH, an independent healthcare safety and quality consultant based in Baltimore, says he’s heard the same complaint for three decades. “It’s what we call the 'Lake Wobegon effect': All of our patients are sicker than average.

“I think it’s just a really poor way to go about what is a very human sort of question,” he adds. “If Mrs. Jones is back in the hospital because she didn’t understand the discharge instructions, the question is not ‘Does my population have more literacy problems than somebody else’s population of patients?’ The question is ‘What can we do for Mrs. Jones so she can understand this stuff?’ ” (For help communicating with patients, check out SHM's on-demand webinar, "Implementing Teach Back as a System-Wide Patient Communication Strategy.")

Healthcare experts say it’s not difficult to find challenges unique to particular urban areas or populations. Florida Hospital Association President Bruce Rueben, MBA, says many Floridians speak English as a second language, making clear communication critical. The state also has one of the highest percentages of elderly residents and is in a funding crisis that has required providers to do more with less. But instead of worrying about exceptions or anomalies, Rueben says, focusing on the best overall readmission-reducing approaches will help ensure that all patients are being treated and discharged effectively.

What about dealing with specific conditions? Paul McGann, MD, deputy chief medical officer at the Centers for Medicare & Medicaid Services (CMS), says good evidence exists for the effectiveness of interventions aimed at diseases ranging from congestive heart failure and cancer to chronic obstructive lung disease, ulcers, and stroke. But data from Medicare’s Care Transitions Program, he says, suggest that even if all hospitals pursued the dozens of disease-specific interventions collectively implemented by the program’s participants, they still wouldn’t address more than about half of the causes of readmission. Based on that finding, he says, project leaders have insisted on an all-cause focus.

Dr. Halasyamani says it’s only natural to sometimes focus on the exception rather than the rule. “And we’ve all had those experiences where, boy, you feel like you’ve done everything you can and the patient still comes back,” she says. “But having said that, we also have opportunities where we haven’t done everything that we can and the patient comes back. So I think we need to focus on that first, rather than say, ‘Well, this isn’t fixable based on all of the patient-level issues.’”

Rachel George, MD, MBA, FHM, regional medical director and vice president of operations for West Cogent Healthcare Inc., says it all comes down to perspective. “Instead of looking at what’s the percentage that we can’t deal with,” she says, “let’s look at the patient population that we can affect.”

Bryn Nelson is a freelance medical writer based in Seattle.

References

1. Allaudeen N, Vidyarthi A, Maselli J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60.

2. Mudge AM, Kasper KM, Clair, A, et al. Recurrent readmissions in medical patients: a prospective study. J Hosp Med. 2011;6(2):61-67.

3. Raven, MC, Billings, JC, Goldfrank LR, Manheimer ED, Gourevitch MN. Medicaid patients at high risk for frequent hospital admission: real-time identification and remediable risks. J Urb Health. 2009;86(2):230-241.

Which patients are you most likely to see again? It’s a particularly vexing question for hospitalists amid the heightened focus on lowering hospital readmissions, and one that several recent studies have sought to address.

One Journal of Hospital Medicine analysis of more than 10,300 admissions found that unplanned rehospitalizations within 30 days of discharge were far more likely for African-American patients and those on high-risk medications like narcotics and corticosteroids.¹ Patients with such chronic conditions as cancer, renal failure, and congestive heart failure also were at increased risk.

A second, smaller study of 142 inpatients who had been hospitalized within the preceding six months found that chronic disease, depression, and being underweight or obese all predicted a higher risk of another readmission within the next six months.²

And a third report in the Journal of Urban Health examined more than 36,000 Medicare patients admitted to urban public hospitals to assess which were most likely to return within the following year. Chronic medical conditions, substance abuse, and homelessness all contributed to increased odds.³

Whenever there is a program that has financial incentives, people always get concerned that they have patients who are somehow different. Inherent in that assumption is: more difficult to manage or sicker or more complicated.—Lakshmi Halasyamani, MD, SFHM, SHM board member, vice president for medical affairs, Saint Joseph Mercy Health System, Ann Arbor, Mich.

Most efforts aimed at reducing rehospitalizations, such as SHM’s Project BOOST, include a risk assessment that can point to potential trouble spots for individual patients. For certain populations, research has highlighted socioeconomic and racial disparities in access to healthcare that likely lead to unnecessary hospitalizations. But it’s one thing to identify the factors associated with higher rates, and quite another to actively manage them, especially when many crop up well beyond a hospital’s walls. Anxiety over these contributing factors is steadily building in anticipation of Medicare penalties for excessively high readmission rates set to begin in 2012.

“Whenever there is a program that has financial incentives, people always get concerned that they have patients who are somehow different,” says Lakshmi Halasyamani, MD, SFHM, SHM board member and vice president for medical affairs at Saint Joseph Mercy Health System in Ann Arbor, Mich. “Inherent in that assumption is: more difficult to manage or sicker or more complicated.”

Stephen Jencks, MD, MPH, an independent healthcare safety and quality consultant based in Baltimore, says he’s heard the same complaint for three decades. “It’s what we call the 'Lake Wobegon effect': All of our patients are sicker than average.

“I think it’s just a really poor way to go about what is a very human sort of question,” he adds. “If Mrs. Jones is back in the hospital because she didn’t understand the discharge instructions, the question is not ‘Does my population have more literacy problems than somebody else’s population of patients?’ The question is ‘What can we do for Mrs. Jones so she can understand this stuff?’ ” (For help communicating with patients, check out SHM's on-demand webinar, "Implementing Teach Back as a System-Wide Patient Communication Strategy.")

Healthcare experts say it’s not difficult to find challenges unique to particular urban areas or populations. Florida Hospital Association President Bruce Rueben, MBA, says many Floridians speak English as a second language, making clear communication critical. The state also has one of the highest percentages of elderly residents and is in a funding crisis that has required providers to do more with less. But instead of worrying about exceptions or anomalies, Rueben says, focusing on the best overall readmission-reducing approaches will help ensure that all patients are being treated and discharged effectively.

What about dealing with specific conditions? Paul McGann, MD, deputy chief medical officer at the Centers for Medicare & Medicaid Services (CMS), says good evidence exists for the effectiveness of interventions aimed at diseases ranging from congestive heart failure and cancer to chronic obstructive lung disease, ulcers, and stroke. But data from Medicare’s Care Transitions Program, he says, suggest that even if all hospitals pursued the dozens of disease-specific interventions collectively implemented by the program’s participants, they still wouldn’t address more than about half of the causes of readmission. Based on that finding, he says, project leaders have insisted on an all-cause focus.

Dr. Halasyamani says it’s only natural to sometimes focus on the exception rather than the rule. “And we’ve all had those experiences where, boy, you feel like you’ve done everything you can and the patient still comes back,” she says. “But having said that, we also have opportunities where we haven’t done everything that we can and the patient comes back. So I think we need to focus on that first, rather than say, ‘Well, this isn’t fixable based on all of the patient-level issues.’”

Rachel George, MD, MBA, FHM, regional medical director and vice president of operations for West Cogent Healthcare Inc., says it all comes down to perspective. “Instead of looking at what’s the percentage that we can’t deal with,” she says, “let’s look at the patient population that we can affect.”

Bryn Nelson is a freelance medical writer based in Seattle.

References

1. Allaudeen N, Vidyarthi A, Maselli J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60.

2. Mudge AM, Kasper KM, Clair, A, et al. Recurrent readmissions in medical patients: a prospective study. J Hosp Med. 2011;6(2):61-67.

3. Raven, MC, Billings, JC, Goldfrank LR, Manheimer ED, Gourevitch MN. Medicaid patients at high risk for frequent hospital admission: real-time identification and remediable risks. J Urb Health. 2009;86(2):230-241.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

The Food and Drug Administration has approved a first-line maintenance indication for rituximab in advanced follicular lymphoma, according to an announcement by Genentech and Biogen Idec.

The indication specifies that maintenance rituximab (Rituxan) may be used in patients with advanced follicular lymphoma who responded to induction treatment with rituximab plus chemotherapy. The European Commission approved the same indication in October 2010, according to the January 28 announcement.

The application for a maintenance rituximab treatment was supported by results of the phase III PRIMA study, a randomized international trial conducted by the Groupe d’Etude des Lymphomes de l’Adulte (GELA). The trial in 1,217 patients with advanced follicular lymphoma not previously treated showed that two years of maintenance therapy cut their risk of relapse in half compared with observation

GELA, the European Organisation for Research and Treatment of Cancer (EORTC)’s adult lymphoma study group, had reported the progression-free survival rate among 505 patients randomized to maintenance with rituximab (Rituxan in the United States, MabThera in Europe) was 82% at 2 years vs. 66% for 513 patients randomized to observation only (hazard ratio 0.50, stratified log-rank, P less than .0001). Rituximab maintenance reduced by 39% the need for patients to be started on new antilymphoma therapies (HR 0.61, P less than .0003), according to GELA’s presentation at the American Society for Clinical Oncology’s 2010 annual meeting.

All patients in the trial received rituximab in their induction regimens: 75% had R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone); 22% R-CVP (rituximab plus cyclophosphamide, vincristine, and prednisone), and 3% R-FCM (rituximab plus fludarabine, cyclophosphamide, and mitoxantrone). Patients randomized to maintenance rituximab received it for 2 years as a single agent.

Investigators said rituximab maintenance was generally well tolerated, with grade 3 or 4 adverse events occurring in 22% of patients. The most common were infections in 37% of patients on maintenance and 22% of those on observation. Grade 3 or 4 neutropenia and low white blood cell count each occurred in about 4% of patients on maintenance rituximab.

The trial was sponsored by Roche, which markets rituximab outside the United States and is the parent company of Genentech.

But some have long suspected too-aggressive treatment would have an adverse effect—the so called “J curve” seen when drug effect is plotted against adverse outcome. The validity of this concept at the extreme is obvious: excessive hypotension or hypoglycemia is not clinically tolerated. So where is the cutoff between benefit and complications, where treatment becomes too aggressive and causes complications that outweigh the benefits?

In this issue of the Journal, Dr. Edward J. Filippone and colleagues discuss the treatment of hypertension with proposed aggressive but seemingly reasonable blood pressure targets. Surprisingly, interventional trials have not jibed with observational data that suggest a beneficial continuous relationship between blood-pressure-lowering within the physiologic range and cardiac outcomes. Potential explanations for this are many. Organs differ in their response to blood-pressure-lowering. The brain, despite considerable autoregulatory circulatory control, benefits from lowered blood pressure with reduced stroke frequency. The heart, uniquely dependent on diastolic flow for perfusion, can be compromised with aggressive lowering of the diastolic pressure, ie, to below 85 mm Hg, although lowering the systolic pressure may be beneficial. Specific drugs may have beneficial or detrimental effects, particularly in combinations needed to control blood pressure in patients with stiff arteries and multiple comorbidities.

In the clinic, attention to the individual’s physiology and clinical response to therapy needs to be paramount in our mind as we determine treatment targets—possibly a source of dissonance, as we are held accountable to external agencies for our practice performance in a depersonalized manner.

Proposed aggressive blood pressure targets remain contentious, but a far greater problem is that we are still not successfully treating hypertension to even a conservative target. In a recent analysis of the National Health and Nutrition Examination Survey database from 2003 to 2006, only about 44% of treated hypertensive patients were appropriately controlled.¹ As a community of physicians, we have a way to go before we hit the J point.

But some have long suspected too-aggressive treatment would have an adverse effect—the so called “J curve” seen when drug effect is plotted against adverse outcome. The validity of this concept at the extreme is obvious: excessive hypotension or hypoglycemia is not clinically tolerated. So where is the cutoff between benefit and complications, where treatment becomes too aggressive and causes complications that outweigh the benefits?

In this issue of the Journal, Dr. Edward J. Filippone and colleagues discuss the treatment of hypertension with proposed aggressive but seemingly reasonable blood pressure targets. Surprisingly, interventional trials have not jibed with observational data that suggest a beneficial continuous relationship between blood-pressure-lowering within the physiologic range and cardiac outcomes. Potential explanations for this are many. Organs differ in their response to blood-pressure-lowering. The brain, despite considerable autoregulatory circulatory control, benefits from lowered blood pressure with reduced stroke frequency. The heart, uniquely dependent on diastolic flow for perfusion, can be compromised with aggressive lowering of the diastolic pressure, ie, to below 85 mm Hg, although lowering the systolic pressure may be beneficial. Specific drugs may have beneficial or detrimental effects, particularly in combinations needed to control blood pressure in patients with stiff arteries and multiple comorbidities.

In the clinic, attention to the individual’s physiology and clinical response to therapy needs to be paramount in our mind as we determine treatment targets—possibly a source of dissonance, as we are held accountable to external agencies for our practice performance in a depersonalized manner.

Proposed aggressive blood pressure targets remain contentious, but a far greater problem is that we are still not successfully treating hypertension to even a conservative target. In a recent analysis of the National Health and Nutrition Examination Survey database from 2003 to 2006, only about 44% of treated hypertensive patients were appropriately controlled.¹ As a community of physicians, we have a way to go before we hit the J point.

But some have long suspected too-aggressive treatment would have an adverse effect—the so called “J curve” seen when drug effect is plotted against adverse outcome. The validity of this concept at the extreme is obvious: excessive hypotension or hypoglycemia is not clinically tolerated. So where is the cutoff between benefit and complications, where treatment becomes too aggressive and causes complications that outweigh the benefits?

In this issue of the Journal, Dr. Edward J. Filippone and colleagues discuss the treatment of hypertension with proposed aggressive but seemingly reasonable blood pressure targets. Surprisingly, interventional trials have not jibed with observational data that suggest a beneficial continuous relationship between blood-pressure-lowering within the physiologic range and cardiac outcomes. Potential explanations for this are many. Organs differ in their response to blood-pressure-lowering. The brain, despite considerable autoregulatory circulatory control, benefits from lowered blood pressure with reduced stroke frequency. The heart, uniquely dependent on diastolic flow for perfusion, can be compromised with aggressive lowering of the diastolic pressure, ie, to below 85 mm Hg, although lowering the systolic pressure may be beneficial. Specific drugs may have beneficial or detrimental effects, particularly in combinations needed to control blood pressure in patients with stiff arteries and multiple comorbidities.

In the clinic, attention to the individual’s physiology and clinical response to therapy needs to be paramount in our mind as we determine treatment targets—possibly a source of dissonance, as we are held accountable to external agencies for our practice performance in a depersonalized manner.

Proposed aggressive blood pressure targets remain contentious, but a far greater problem is that we are still not successfully treating hypertension to even a conservative target. In a recent analysis of the National Health and Nutrition Examination Survey database from 2003 to 2006, only about 44% of treated hypertensive patients were appropriately controlled.¹ As a community of physicians, we have a way to go before we hit the J point.

Medical tourism is on the rise,¹ and since medical tourists are often very important persons (VIPs), hospital-based physicians may be more likely to care for celebrities, royalty, and political leaders. But even in hospitals that do not see medical tourists, physicians will often care for VIP patients such as hospital trustees and board members, prominent physicians, and community leaders.^2–4

However, caring for VIPs raises special issues and challenges. In a situation often referred to as the “VIP syndrome,”^5–9 a patient’s special social or political status—or our perceptions of it—induces changes in behaviors and clinical practice that create a “vicious circle of VIP pressure and staff withdrawal”⁹ that can lead to poor outcomes.

Based on their experience caring for three American presidents, Mariano and McLeod⁷ offered three directives for caring for VIPs:

• Vow to value your medical skills and judgment
• Intend to command the medical aspects of the situation
• Practice medicine the same way for all your patients.⁷

In this paper, we hope to extend the sparse literature on the VIP syndrome by proposing nine principles of caring for VIPs, with recommendations specific to the type of VIP where applicable.

PRINCIPLE 1: DON’T BEND THE RULES

Caring for VIPs creates pressures to change usual clinical wisdom and practices. But it is essential to resist changing time-honored, effective clinical judgment and practices.

To preserve usual clinical practice, clinicians must be constantly vigilant as to whether their judgment is being clouded by the circumstances. As Smith and Shesser noted in 1988, “Since the standard operating procedures […] are designed for the efficient delivery of high-quality care, any deviation from these procedures increases the possibility that care may be compromised.”⁵ In other words, suspending usual practice when caring for a VIP patient can imperil the patient.^2–5,10,11 When caring for VIP physicians, for example, circumventing usual medical and administrative routines and the difficulties that caring for colleagues poses for nurses and physicians have led to poor medical care and outcomes, as well as to hostility.^2–4

A striking example of the potential effects of VIP syndrome is the death of Eleanor Roosevelt from miliary tuberculosis acutissima: she was misdiagnosed with aplastic anemia on the basis of only the results of a bone marrow aspirate study, and she was treated with steroids. The desire to spare this VIP patient the discomfort of a bone marrow biopsy, on which tuberculous granulomata were more likely to have been seen, caused the true diagnosis to be missed and resulted in the administration of a hazardous medication.¹¹ The hard lesson here is that we must resist the pressure to simplify or change customary medical care to avoid causing a VIP patient discomfort or putting the patient through a complex procedure.

We recommend discussing these issues explicitly with the VIP patient and family at the outset so that everyone can appreciate the importance of usual care. An early conversation can communicate the clinician’s experience in the care of such patients and can be reassuring. As Smith and Shesser noted, “Usually, the VIP is relieved if the physician states explicitly, ‘I am going to treat you as I would any other patient.’ ”⁵

PRINCIPLE 2: WORK AS A TEAM, NOT IN ‘SILOS’

Teamwork is essential for good clinical outcomes, ^12–14 especially when the clinical problem is complex, as is often the case when people travel long distances to receive care. All consultants involved in the patient’s care must not only attend to their own clinical issues but also communicate amply with their colleagues.

At the same time, we must recognize that medical practice “is not a committee process; it must be clear at all times which physician is responsible for directing clinical care.”⁵ One physician must be in charge of the overall care. Seeking the input of other physicians must not be allowed to diffuse responsibility. The primary attending physician must speak with the consultants, summarize their views, and then communicate the findings and the plan of care to the patient and family.

Paradoxically, teamwork can be challenged when circumstances lead consultants to defer communicating directly with the family in favor of the primary physician’s doing so. Similarly, consultants must avoid any temptation to simply “do their thing” and not communicate with one another, thereby potentially offering “siloed,” discoordinated care.

We propose designating a primary physician to take charge of the care and the communication. This physician must have the time to talk with each team member about how best to communicate the individual findings to the patient and family. At times, the primary physician may also ask the consultants to communicate directly with the patient and family when needed.

PRINCIPLE 3: COMMUNICATE, COMMUNICATE, COMMUNICATE

As a corollary of principle 2, heightened communication is essential when caring for VIP patients. Communication should include the patient, the family, visiting physicians who accompany the patient, and the physicians providing care. Communicating with the media and with other uninvolved individuals is addressed in principle 4.

The logistic and security challenges of transporting VIP patients through the hospital for tests or therapy demand increased communication. Scheduling a computed tomographic scan may involve arranging an off-hours appointment in the radiology department (to minimize security risks and disruption to other patients’ schedules), assuring the off-hours availability of allied health providers to accompany the patient, alerting hospital security, and discussing the appointment with the patient and the patient’s entourage.

PRINCIPLE 4: CAREFULLY MANAGE COMMUNICATION WITH THE MEDIA

Although the news media and the public may demand medical information about patients who are celebrities, political luminaries, or royalty, the confidentiality of the physician-patient relationship must be protected. The release of health information is at the sole discretion of the patient or a designated surrogate.

The care of President Ronald Reagan after the 1981 assassination attempt is a benchmark of how to release information to the public.¹⁰ A single physician held regularly scheduled press conferences, and these were intentionally held away from the site of the President’s care.

Designating a senior hospital physician to communicate with the media is desirable, and the physician-spokesperson can call on specialists from the patient care team (eg, a critical care physician), when appropriate, to provide further information.

Early implementation of an explicit and structured media communication plan is advisable, especially when the VIP patient is a political or royal figure for whom public clamor for information will be vigorous. A successful communication strategy balances the public’s demand for information with the need to protect the patient’s confidentiality.

PRINCIPLE 5: RESIST ‘CHAIRPERSON’S SYNDROME’

“Chairperson’s syndrome”⁵ is pressure for the VIP patient to be cared for by the department chairperson. The pressure may come from the patient, family, or attendants, who may assume that the chairperson is the best doctor for the clinical circumstance. The pressure may also come from the chairperson, who feels the need to “take command” in a situation with high visibility. Nevertheless, designation of a chairperson to care for a VIP patient is appropriate only when the chairperson is indeed the clinician who has the most expertise in the patient’s clinical issues.

As in principle 1, in academic medical centers, we encourage the participation of trainees in the care of VIP patients because excluding them could disrupt the usual flow of care, and because trainees offer a currency and facility with the nuances of hospital practice and routine that are advantageous to the patient’s care.

PRINCIPLE 6: CARE SHOULD OCCUR WHERE IT IS MOST APPROPRIATE

Decisions about where to place the VIP patient during the medical visit can fall victim to the VIP syndrome if the expectations of the patient or family conflict with usual clinical practice and judgment about the optimal care venue.

For example, caring for the patient in a setting away from the mainstream clinical environment may offer the appeal of privacy or enhanced security but can under some circumstances impede optimal care, including prolonging the response time during emergencies and disrupting the optimal care routine and teamwork of allied health providers.

Critical care services and monitoring are best provided in the intensive care unit, and attempts to relocate the patient away from the intensive care unit should be resisted. We recommend a candid discussion of the importance of keeping the patient in the intensive care unit to ensure optimal care by a seasoned clinical team with short response times if urgencies should arise.

At the same time, a request to transfer a VIP patient to a special setting designed for private care with special amenities (eg, appealing room decor, adjacent sleeping rooms for family members, enhanced security) available in some hospitals^15–16 can be honored as soon as the patient’s condition permits. The benefits of such amenities are often greatly appreciated and can reduce stress and thereby promote recovery. The benefits of enhanced security in sequestered venues may especially drive the decision to move when clinically prudent (see principle 7).

PRINCIPLE 7: PROTECT THE PATIENT’S SECURITY

Providing security is another essential part of caring for VIPs, especially celebrities, political figures, and royalty. Protecting the patient from bodily harm requires special attention to the patient’s location, caregiver access, and other logistic matters.

As indicated in principle 6, the patient’s clinical needs are paramount in determining where the patient receives care. If the patient requires care in a mainstream hospital location such as the intensive care unit, modifications of the unit may be needed to alter access, to accommodate security personnel, and to restrict caregivers’ access to the patient. Modifications include structural changes to windows, special credentials (eg, badges) for essential providers, arranging transports within the hospital for elective procedures during off-hours, and providing around-the-clock security personnel near the patient.

As important as it is to protect VIP patients from bodily harm during the visit, it is equally important to protect them from attacks on confidentiality via unauthorized access to the electronic medical record, and this is perhaps the more difficult challenge, as examples of breaches abound.^10,17–19 Although the duty to protect against these breaches rests with the hospital, the use of “pop-ups” in the electronic medical record can flash a warning that only employees with legitimate clinical reasons should access the record. These warnings should also cite the penalties for unauthorized review of the record, which is supported by the Health Insurance Portability and Accountability Act (HIPAA). Access to celebrities’ health records could be restricted to a few predetermined health care providers.

PRINCIPLE 8: BE CAREFUL ABOUT ACCEPTING OR DECLINING GIFTS

VIP patients often present gifts to physicians, and giving gifts to doctors is a common and long-standing practice.^20,21 Patients offer gifts out of gratitude, affection, desperation, or the desire to garner special treatment or indebtedness. VIP patients from gifting cultures may be especially likely to offer gifts to their providers, and the gifts can be lavish.

The “ethical calculus”²¹ of whether to accept or decline a gift depends on the circumstances and on what motivates the offer, and the physician needs to consider the patient’s reasons for giving the gift.

In general, gifts should be accepted only with caution during the acute episode of care. The acceptance of a gift from a VIP patient or family member may be interpreted by the gift-giver as a sort of unspoken promise, and this misunderstanding may strain the physician-patient relationship, especially if the clinical course deteriorates.

Rather than accept a gift during an episode of acute care, we suggest that the physician graciously decline the gift and offer to accept the gift at the end of the episode of acute care—that is, if the offerer still feels so inclined and remembers. Explaining the reason for deferring the gift can decrease the risk of misunderstandings or of unmet expectations by the gift-giver. Also, deferring the acceptance of a gift allows the caregiver to affirm the commitment to excellent care that is free of gifts, thereby ensuring that the patient will be confident of a similar level of care by providers who have not been offered gifts.

On the other hand, declining a gift may cause more damage than accepting it, particularly if the VIP patient is from a culture in which refusing a gift is impolite.²² A sensible compromise may be to adopt the recommendations of the American Academy of Pediatrics²³—ie, attempt to appreciate appropriate gifts and graciously refuse those that are not.

PRINCIPLE 9: WORKING WITH THE PATIENT’S PERSONAL PHYSICIANS

VIP patients, perhaps especially royalty, may be accompanied by their own physicians and may also wish to bring in consultants from other institutions. Though this outside involvement poses challenges (eg, providing access to medical records, arranging briefings, attending bedside rounds), we believe it should be encouraged when the issue is raised. Furthermore, institutions and caregivers should anticipate these requests and identify potential outside consultants whose names can be volunteered if the issue arises.

Again, if VIP patients wish to involve physicians from outside the institution where they are receiving care, this should not be viewed as an expression of doubt about the care being received. Rather, we prefer to view it as an opportunity to validate current management or to entertain alternative approaches. Most often, when an outside consultant confirms the current medical care, this can have the beneficial effect of increasing confidence and facilitating management.

In a similar way, when VIP patients bring their own physician, whose judgment and care they trust, this represents an opportunity to engage the patient’s trusted physician-advisor in clinical decision-making and thus optimize communication with the patient. Collegial interactions with these physician-colleagues can facilitate communication and decision-making for the patient.

Medical tourism is on the rise,¹ and since medical tourists are often very important persons (VIPs), hospital-based physicians may be more likely to care for celebrities, royalty, and political leaders. But even in hospitals that do not see medical tourists, physicians will often care for VIP patients such as hospital trustees and board members, prominent physicians, and community leaders.^2–4

However, caring for VIPs raises special issues and challenges. In a situation often referred to as the “VIP syndrome,”^5–9 a patient’s special social or political status—or our perceptions of it—induces changes in behaviors and clinical practice that create a “vicious circle of VIP pressure and staff withdrawal”⁹ that can lead to poor outcomes.

Based on their experience caring for three American presidents, Mariano and McLeod⁷ offered three directives for caring for VIPs:

• Vow to value your medical skills and judgment
• Intend to command the medical aspects of the situation
• Practice medicine the same way for all your patients.⁷

In this paper, we hope to extend the sparse literature on the VIP syndrome by proposing nine principles of caring for VIPs, with recommendations specific to the type of VIP where applicable.

PRINCIPLE 1: DON’T BEND THE RULES

Caring for VIPs creates pressures to change usual clinical wisdom and practices. But it is essential to resist changing time-honored, effective clinical judgment and practices.

To preserve usual clinical practice, clinicians must be constantly vigilant as to whether their judgment is being clouded by the circumstances. As Smith and Shesser noted in 1988, “Since the standard operating procedures […] are designed for the efficient delivery of high-quality care, any deviation from these procedures increases the possibility that care may be compromised.”⁵ In other words, suspending usual practice when caring for a VIP patient can imperil the patient.^2–5,10,11 When caring for VIP physicians, for example, circumventing usual medical and administrative routines and the difficulties that caring for colleagues poses for nurses and physicians have led to poor medical care and outcomes, as well as to hostility.^2–4

A striking example of the potential effects of VIP syndrome is the death of Eleanor Roosevelt from miliary tuberculosis acutissima: she was misdiagnosed with aplastic anemia on the basis of only the results of a bone marrow aspirate study, and she was treated with steroids. The desire to spare this VIP patient the discomfort of a bone marrow biopsy, on which tuberculous granulomata were more likely to have been seen, caused the true diagnosis to be missed and resulted in the administration of a hazardous medication.¹¹ The hard lesson here is that we must resist the pressure to simplify or change customary medical care to avoid causing a VIP patient discomfort or putting the patient through a complex procedure.

We recommend discussing these issues explicitly with the VIP patient and family at the outset so that everyone can appreciate the importance of usual care. An early conversation can communicate the clinician’s experience in the care of such patients and can be reassuring. As Smith and Shesser noted, “Usually, the VIP is relieved if the physician states explicitly, ‘I am going to treat you as I would any other patient.’ ”⁵

PRINCIPLE 2: WORK AS A TEAM, NOT IN ‘SILOS’

Teamwork is essential for good clinical outcomes, ^12–14 especially when the clinical problem is complex, as is often the case when people travel long distances to receive care. All consultants involved in the patient’s care must not only attend to their own clinical issues but also communicate amply with their colleagues.

At the same time, we must recognize that medical practice “is not a committee process; it must be clear at all times which physician is responsible for directing clinical care.”⁵ One physician must be in charge of the overall care. Seeking the input of other physicians must not be allowed to diffuse responsibility. The primary attending physician must speak with the consultants, summarize their views, and then communicate the findings and the plan of care to the patient and family.

Paradoxically, teamwork can be challenged when circumstances lead consultants to defer communicating directly with the family in favor of the primary physician’s doing so. Similarly, consultants must avoid any temptation to simply “do their thing” and not communicate with one another, thereby potentially offering “siloed,” discoordinated care.

We propose designating a primary physician to take charge of the care and the communication. This physician must have the time to talk with each team member about how best to communicate the individual findings to the patient and family. At times, the primary physician may also ask the consultants to communicate directly with the patient and family when needed.

PRINCIPLE 3: COMMUNICATE, COMMUNICATE, COMMUNICATE

As a corollary of principle 2, heightened communication is essential when caring for VIP patients. Communication should include the patient, the family, visiting physicians who accompany the patient, and the physicians providing care. Communicating with the media and with other uninvolved individuals is addressed in principle 4.

The logistic and security challenges of transporting VIP patients through the hospital for tests or therapy demand increased communication. Scheduling a computed tomographic scan may involve arranging an off-hours appointment in the radiology department (to minimize security risks and disruption to other patients’ schedules), assuring the off-hours availability of allied health providers to accompany the patient, alerting hospital security, and discussing the appointment with the patient and the patient’s entourage.

PRINCIPLE 4: CAREFULLY MANAGE COMMUNICATION WITH THE MEDIA

Although the news media and the public may demand medical information about patients who are celebrities, political luminaries, or royalty, the confidentiality of the physician-patient relationship must be protected. The release of health information is at the sole discretion of the patient or a designated surrogate.

The care of President Ronald Reagan after the 1981 assassination attempt is a benchmark of how to release information to the public.¹⁰ A single physician held regularly scheduled press conferences, and these were intentionally held away from the site of the President’s care.

Designating a senior hospital physician to communicate with the media is desirable, and the physician-spokesperson can call on specialists from the patient care team (eg, a critical care physician), when appropriate, to provide further information.

Early implementation of an explicit and structured media communication plan is advisable, especially when the VIP patient is a political or royal figure for whom public clamor for information will be vigorous. A successful communication strategy balances the public’s demand for information with the need to protect the patient’s confidentiality.

PRINCIPLE 5: RESIST ‘CHAIRPERSON’S SYNDROME’

“Chairperson’s syndrome”⁵ is pressure for the VIP patient to be cared for by the department chairperson. The pressure may come from the patient, family, or attendants, who may assume that the chairperson is the best doctor for the clinical circumstance. The pressure may also come from the chairperson, who feels the need to “take command” in a situation with high visibility. Nevertheless, designation of a chairperson to care for a VIP patient is appropriate only when the chairperson is indeed the clinician who has the most expertise in the patient’s clinical issues.

As in principle 1, in academic medical centers, we encourage the participation of trainees in the care of VIP patients because excluding them could disrupt the usual flow of care, and because trainees offer a currency and facility with the nuances of hospital practice and routine that are advantageous to the patient’s care.

PRINCIPLE 6: CARE SHOULD OCCUR WHERE IT IS MOST APPROPRIATE

Decisions about where to place the VIP patient during the medical visit can fall victim to the VIP syndrome if the expectations of the patient or family conflict with usual clinical practice and judgment about the optimal care venue.

For example, caring for the patient in a setting away from the mainstream clinical environment may offer the appeal of privacy or enhanced security but can under some circumstances impede optimal care, including prolonging the response time during emergencies and disrupting the optimal care routine and teamwork of allied health providers.

Critical care services and monitoring are best provided in the intensive care unit, and attempts to relocate the patient away from the intensive care unit should be resisted. We recommend a candid discussion of the importance of keeping the patient in the intensive care unit to ensure optimal care by a seasoned clinical team with short response times if urgencies should arise.

At the same time, a request to transfer a VIP patient to a special setting designed for private care with special amenities (eg, appealing room decor, adjacent sleeping rooms for family members, enhanced security) available in some hospitals^15–16 can be honored as soon as the patient’s condition permits. The benefits of such amenities are often greatly appreciated and can reduce stress and thereby promote recovery. The benefits of enhanced security in sequestered venues may especially drive the decision to move when clinically prudent (see principle 7).

PRINCIPLE 7: PROTECT THE PATIENT’S SECURITY

Providing security is another essential part of caring for VIPs, especially celebrities, political figures, and royalty. Protecting the patient from bodily harm requires special attention to the patient’s location, caregiver access, and other logistic matters.

As indicated in principle 6, the patient’s clinical needs are paramount in determining where the patient receives care. If the patient requires care in a mainstream hospital location such as the intensive care unit, modifications of the unit may be needed to alter access, to accommodate security personnel, and to restrict caregivers’ access to the patient. Modifications include structural changes to windows, special credentials (eg, badges) for essential providers, arranging transports within the hospital for elective procedures during off-hours, and providing around-the-clock security personnel near the patient.

As important as it is to protect VIP patients from bodily harm during the visit, it is equally important to protect them from attacks on confidentiality via unauthorized access to the electronic medical record, and this is perhaps the more difficult challenge, as examples of breaches abound.^10,17–19 Although the duty to protect against these breaches rests with the hospital, the use of “pop-ups” in the electronic medical record can flash a warning that only employees with legitimate clinical reasons should access the record. These warnings should also cite the penalties for unauthorized review of the record, which is supported by the Health Insurance Portability and Accountability Act (HIPAA). Access to celebrities’ health records could be restricted to a few predetermined health care providers.

PRINCIPLE 8: BE CAREFUL ABOUT ACCEPTING OR DECLINING GIFTS

VIP patients often present gifts to physicians, and giving gifts to doctors is a common and long-standing practice.^20,21 Patients offer gifts out of gratitude, affection, desperation, or the desire to garner special treatment or indebtedness. VIP patients from gifting cultures may be especially likely to offer gifts to their providers, and the gifts can be lavish.

The “ethical calculus”²¹ of whether to accept or decline a gift depends on the circumstances and on what motivates the offer, and the physician needs to consider the patient’s reasons for giving the gift.

In general, gifts should be accepted only with caution during the acute episode of care. The acceptance of a gift from a VIP patient or family member may be interpreted by the gift-giver as a sort of unspoken promise, and this misunderstanding may strain the physician-patient relationship, especially if the clinical course deteriorates.

Rather than accept a gift during an episode of acute care, we suggest that the physician graciously decline the gift and offer to accept the gift at the end of the episode of acute care—that is, if the offerer still feels so inclined and remembers. Explaining the reason for deferring the gift can decrease the risk of misunderstandings or of unmet expectations by the gift-giver. Also, deferring the acceptance of a gift allows the caregiver to affirm the commitment to excellent care that is free of gifts, thereby ensuring that the patient will be confident of a similar level of care by providers who have not been offered gifts.

On the other hand, declining a gift may cause more damage than accepting it, particularly if the VIP patient is from a culture in which refusing a gift is impolite.²² A sensible compromise may be to adopt the recommendations of the American Academy of Pediatrics²³—ie, attempt to appreciate appropriate gifts and graciously refuse those that are not.

PRINCIPLE 9: WORKING WITH THE PATIENT’S PERSONAL PHYSICIANS

VIP patients, perhaps especially royalty, may be accompanied by their own physicians and may also wish to bring in consultants from other institutions. Though this outside involvement poses challenges (eg, providing access to medical records, arranging briefings, attending bedside rounds), we believe it should be encouraged when the issue is raised. Furthermore, institutions and caregivers should anticipate these requests and identify potential outside consultants whose names can be volunteered if the issue arises.

Again, if VIP patients wish to involve physicians from outside the institution where they are receiving care, this should not be viewed as an expression of doubt about the care being received. Rather, we prefer to view it as an opportunity to validate current management or to entertain alternative approaches. Most often, when an outside consultant confirms the current medical care, this can have the beneficial effect of increasing confidence and facilitating management.

In a similar way, when VIP patients bring their own physician, whose judgment and care they trust, this represents an opportunity to engage the patient’s trusted physician-advisor in clinical decision-making and thus optimize communication with the patient. Collegial interactions with these physician-colleagues can facilitate communication and decision-making for the patient.

Medical tourism is on the rise,¹ and since medical tourists are often very important persons (VIPs), hospital-based physicians may be more likely to care for celebrities, royalty, and political leaders. But even in hospitals that do not see medical tourists, physicians will often care for VIP patients such as hospital trustees and board members, prominent physicians, and community leaders.^2–4

However, caring for VIPs raises special issues and challenges. In a situation often referred to as the “VIP syndrome,”^5–9 a patient’s special social or political status—or our perceptions of it—induces changes in behaviors and clinical practice that create a “vicious circle of VIP pressure and staff withdrawal”⁹ that can lead to poor outcomes.

Based on their experience caring for three American presidents, Mariano and McLeod⁷ offered three directives for caring for VIPs:

• Vow to value your medical skills and judgment
• Intend to command the medical aspects of the situation
• Practice medicine the same way for all your patients.⁷

In this paper, we hope to extend the sparse literature on the VIP syndrome by proposing nine principles of caring for VIPs, with recommendations specific to the type of VIP where applicable.

PRINCIPLE 1: DON’T BEND THE RULES

Caring for VIPs creates pressures to change usual clinical wisdom and practices. But it is essential to resist changing time-honored, effective clinical judgment and practices.

To preserve usual clinical practice, clinicians must be constantly vigilant as to whether their judgment is being clouded by the circumstances. As Smith and Shesser noted in 1988, “Since the standard operating procedures […] are designed for the efficient delivery of high-quality care, any deviation from these procedures increases the possibility that care may be compromised.”⁵ In other words, suspending usual practice when caring for a VIP patient can imperil the patient.^2–5,10,11 When caring for VIP physicians, for example, circumventing usual medical and administrative routines and the difficulties that caring for colleagues poses for nurses and physicians have led to poor medical care and outcomes, as well as to hostility.^2–4

A striking example of the potential effects of VIP syndrome is the death of Eleanor Roosevelt from miliary tuberculosis acutissima: she was misdiagnosed with aplastic anemia on the basis of only the results of a bone marrow aspirate study, and she was treated with steroids. The desire to spare this VIP patient the discomfort of a bone marrow biopsy, on which tuberculous granulomata were more likely to have been seen, caused the true diagnosis to be missed and resulted in the administration of a hazardous medication.¹¹ The hard lesson here is that we must resist the pressure to simplify or change customary medical care to avoid causing a VIP patient discomfort or putting the patient through a complex procedure.

We recommend discussing these issues explicitly with the VIP patient and family at the outset so that everyone can appreciate the importance of usual care. An early conversation can communicate the clinician’s experience in the care of such patients and can be reassuring. As Smith and Shesser noted, “Usually, the VIP is relieved if the physician states explicitly, ‘I am going to treat you as I would any other patient.’ ”⁵

PRINCIPLE 2: WORK AS A TEAM, NOT IN ‘SILOS’

Teamwork is essential for good clinical outcomes, ^12–14 especially when the clinical problem is complex, as is often the case when people travel long distances to receive care. All consultants involved in the patient’s care must not only attend to their own clinical issues but also communicate amply with their colleagues.

At the same time, we must recognize that medical practice “is not a committee process; it must be clear at all times which physician is responsible for directing clinical care.”⁵ One physician must be in charge of the overall care. Seeking the input of other physicians must not be allowed to diffuse responsibility. The primary attending physician must speak with the consultants, summarize their views, and then communicate the findings and the plan of care to the patient and family.

Paradoxically, teamwork can be challenged when circumstances lead consultants to defer communicating directly with the family in favor of the primary physician’s doing so. Similarly, consultants must avoid any temptation to simply “do their thing” and not communicate with one another, thereby potentially offering “siloed,” discoordinated care.

We propose designating a primary physician to take charge of the care and the communication. This physician must have the time to talk with each team member about how best to communicate the individual findings to the patient and family. At times, the primary physician may also ask the consultants to communicate directly with the patient and family when needed.

PRINCIPLE 3: COMMUNICATE, COMMUNICATE, COMMUNICATE

As a corollary of principle 2, heightened communication is essential when caring for VIP patients. Communication should include the patient, the family, visiting physicians who accompany the patient, and the physicians providing care. Communicating with the media and with other uninvolved individuals is addressed in principle 4.

The logistic and security challenges of transporting VIP patients through the hospital for tests or therapy demand increased communication. Scheduling a computed tomographic scan may involve arranging an off-hours appointment in the radiology department (to minimize security risks and disruption to other patients’ schedules), assuring the off-hours availability of allied health providers to accompany the patient, alerting hospital security, and discussing the appointment with the patient and the patient’s entourage.

PRINCIPLE 4: CAREFULLY MANAGE COMMUNICATION WITH THE MEDIA

Although the news media and the public may demand medical information about patients who are celebrities, political luminaries, or royalty, the confidentiality of the physician-patient relationship must be protected. The release of health information is at the sole discretion of the patient or a designated surrogate.

The care of President Ronald Reagan after the 1981 assassination attempt is a benchmark of how to release information to the public.¹⁰ A single physician held regularly scheduled press conferences, and these were intentionally held away from the site of the President’s care.

Designating a senior hospital physician to communicate with the media is desirable, and the physician-spokesperson can call on specialists from the patient care team (eg, a critical care physician), when appropriate, to provide further information.

Early implementation of an explicit and structured media communication plan is advisable, especially when the VIP patient is a political or royal figure for whom public clamor for information will be vigorous. A successful communication strategy balances the public’s demand for information with the need to protect the patient’s confidentiality.

PRINCIPLE 5: RESIST ‘CHAIRPERSON’S SYNDROME’

“Chairperson’s syndrome”⁵ is pressure for the VIP patient to be cared for by the department chairperson. The pressure may come from the patient, family, or attendants, who may assume that the chairperson is the best doctor for the clinical circumstance. The pressure may also come from the chairperson, who feels the need to “take command” in a situation with high visibility. Nevertheless, designation of a chairperson to care for a VIP patient is appropriate only when the chairperson is indeed the clinician who has the most expertise in the patient’s clinical issues.

As in principle 1, in academic medical centers, we encourage the participation of trainees in the care of VIP patients because excluding them could disrupt the usual flow of care, and because trainees offer a currency and facility with the nuances of hospital practice and routine that are advantageous to the patient’s care.

PRINCIPLE 6: CARE SHOULD OCCUR WHERE IT IS MOST APPROPRIATE

Decisions about where to place the VIP patient during the medical visit can fall victim to the VIP syndrome if the expectations of the patient or family conflict with usual clinical practice and judgment about the optimal care venue.

For example, caring for the patient in a setting away from the mainstream clinical environment may offer the appeal of privacy or enhanced security but can under some circumstances impede optimal care, including prolonging the response time during emergencies and disrupting the optimal care routine and teamwork of allied health providers.

Critical care services and monitoring are best provided in the intensive care unit, and attempts to relocate the patient away from the intensive care unit should be resisted. We recommend a candid discussion of the importance of keeping the patient in the intensive care unit to ensure optimal care by a seasoned clinical team with short response times if urgencies should arise.

At the same time, a request to transfer a VIP patient to a special setting designed for private care with special amenities (eg, appealing room decor, adjacent sleeping rooms for family members, enhanced security) available in some hospitals^15–16 can be honored as soon as the patient’s condition permits. The benefits of such amenities are often greatly appreciated and can reduce stress and thereby promote recovery. The benefits of enhanced security in sequestered venues may especially drive the decision to move when clinically prudent (see principle 7).

PRINCIPLE 7: PROTECT THE PATIENT’S SECURITY

Providing security is another essential part of caring for VIPs, especially celebrities, political figures, and royalty. Protecting the patient from bodily harm requires special attention to the patient’s location, caregiver access, and other logistic matters.

As indicated in principle 6, the patient’s clinical needs are paramount in determining where the patient receives care. If the patient requires care in a mainstream hospital location such as the intensive care unit, modifications of the unit may be needed to alter access, to accommodate security personnel, and to restrict caregivers’ access to the patient. Modifications include structural changes to windows, special credentials (eg, badges) for essential providers, arranging transports within the hospital for elective procedures during off-hours, and providing around-the-clock security personnel near the patient.

As important as it is to protect VIP patients from bodily harm during the visit, it is equally important to protect them from attacks on confidentiality via unauthorized access to the electronic medical record, and this is perhaps the more difficult challenge, as examples of breaches abound.^10,17–19 Although the duty to protect against these breaches rests with the hospital, the use of “pop-ups” in the electronic medical record can flash a warning that only employees with legitimate clinical reasons should access the record. These warnings should also cite the penalties for unauthorized review of the record, which is supported by the Health Insurance Portability and Accountability Act (HIPAA). Access to celebrities’ health records could be restricted to a few predetermined health care providers.

PRINCIPLE 8: BE CAREFUL ABOUT ACCEPTING OR DECLINING GIFTS

VIP patients often present gifts to physicians, and giving gifts to doctors is a common and long-standing practice.^20,21 Patients offer gifts out of gratitude, affection, desperation, or the desire to garner special treatment or indebtedness. VIP patients from gifting cultures may be especially likely to offer gifts to their providers, and the gifts can be lavish.

The “ethical calculus”²¹ of whether to accept or decline a gift depends on the circumstances and on what motivates the offer, and the physician needs to consider the patient’s reasons for giving the gift.

In general, gifts should be accepted only with caution during the acute episode of care. The acceptance of a gift from a VIP patient or family member may be interpreted by the gift-giver as a sort of unspoken promise, and this misunderstanding may strain the physician-patient relationship, especially if the clinical course deteriorates.

Rather than accept a gift during an episode of acute care, we suggest that the physician graciously decline the gift and offer to accept the gift at the end of the episode of acute care—that is, if the offerer still feels so inclined and remembers. Explaining the reason for deferring the gift can decrease the risk of misunderstandings or of unmet expectations by the gift-giver. Also, deferring the acceptance of a gift allows the caregiver to affirm the commitment to excellent care that is free of gifts, thereby ensuring that the patient will be confident of a similar level of care by providers who have not been offered gifts.

On the other hand, declining a gift may cause more damage than accepting it, particularly if the VIP patient is from a culture in which refusing a gift is impolite.²² A sensible compromise may be to adopt the recommendations of the American Academy of Pediatrics²³—ie, attempt to appreciate appropriate gifts and graciously refuse those that are not.

PRINCIPLE 9: WORKING WITH THE PATIENT’S PERSONAL PHYSICIANS

VIP patients, perhaps especially royalty, may be accompanied by their own physicians and may also wish to bring in consultants from other institutions. Though this outside involvement poses challenges (eg, providing access to medical records, arranging briefings, attending bedside rounds), we believe it should be encouraged when the issue is raised. Furthermore, institutions and caregivers should anticipate these requests and identify potential outside consultants whose names can be volunteered if the issue arises.

Again, if VIP patients wish to involve physicians from outside the institution where they are receiving care, this should not be viewed as an expression of doubt about the care being received. Rather, we prefer to view it as an opportunity to validate current management or to entertain alternative approaches. Most often, when an outside consultant confirms the current medical care, this can have the beneficial effect of increasing confidence and facilitating management.

In a similar way, when VIP patients bring their own physician, whose judgment and care they trust, this represents an opportunity to engage the patient’s trusted physician-advisor in clinical decision-making and thus optimize communication with the patient. Collegial interactions with these physician-colleagues can facilitate communication and decision-making for the patient.

To begin, obtain a clinical history, perform a physical examination, and order a chest radiograph.

In the history, look for exposure to environmental irritants such as tobacco smoke, allergens, or dust, or medications such as angiotensin-converting enzyme (ACE) inhibitors or oxymetazoline (Afrin). If a potential irritant is present, it should be avoided or stopped immediately.^1–3 If the cough improves partially or fully when exposure to the irritant is stopped, this supports a diagnosis of chronic bronchitis or, in the case of ACE inhibitors, ACE-inhibitor-induced cough. The character of the cough (eg, paroxysmal, loose, dry, or productive¹) has not been shown to be diagnostically useful or specific.

If the chest radiograph is abnormal, then the diagnostic inquiry should be guided by the abnormality. Abnormalities that cause cough include bronchogenic carcinoma, sarcoidosis, and bronchiectasis. If the radiograph is normal, then upper airway cough syndrome, asthma, gastroesophageal reflux disease (GERD), chronic bronchitis, or nonasthmatic eosinophilic bronchitis is more likely.

COMMON CAUSES OF CHRONIC COUGH

Chronic bronchitis

As noted above, a history of exposure to an irritant suggests this diagnosis.

Upper airway cough syndrome

Upper airway cough syndrome (formerly known as postnasal drip) is due to chronic upper respiratory tract irritation and hypersensitivity of cough receptors.^3,4 Sources of irritation vary and include sinusitis and any form of rhinitis: allergic and nonallergic, postinfectious, environmental irritant-induced, vasomotor, and drug-induced.

Patients complain of postnasal drip or frequent clearing of the throat. On physical examination one can see mucus in the oropharnyx or a cobblestone appearance. However, these symptoms and signs are not specific and may be absent.

A therapeutic trial is warranted, but be aware that different rhinitides respond to specific treatments:

• Histamine-mediated or allergic rhinitis will respond to allergen avoidance, new-generation antihistamines such as loratadine (Claritin), mast cell stabilizers such as cromolyn (Intal), and intranasal glucocorticoids such as fluticasone (Flovent).^4,5
• Nonhistamine-mediated rhinitides (the common cold and perennial nonallergic rhinitis) respond to older-generation antihistamines such as diphenhydramine (Benadryl) and decongestant combinations. If these cannot be used, intranasal glucocorticoids and ipratropium (Atrovent) are alternatives.
• Vasomotor rhinitis will respond to intranasal ipratropium 0.3% for 3 weeks and then as required.
• Postinfective rhinitis, ie, a cough that began as severe bronchitis, would warrant an antihistamine-decongestant combination.

With adequate treatment, the cough should improve after 1 to 2 weeks; if rhinosinus symptoms persist, consider bacterial sinusitis and obtain radiographs of the sinuses. If imaging shows mucosal thickening (> 5 mm) or an air-fluid level, treat with decongestants and antibiotics for 3 weeks.^1,4,5

 

 

Gastroesophageal reflux disease

GERD is another common cause of cough, and the most difficult to exclude.⁵ Look for a history of reflux or heartburn and positional coughing, and have a low threshold for beginning empiric therapy. Indeed, according to the 2006 American College of Chest Physicians Cough Guideline Committee,^5,6 should a patient arrive in your clinic with a chronic cough and a normal chest radiograph who does not smoke and is not on an ACE inhibitor, then you should start empiric reflux therapy. Begin with lifestyle changes, acid suppression, and prokinetics. The cough may take 1 to 2 months before it begins to improve, and even longer to resolve.

The gold standard for diagnosis is 24-hour pH and impedance monitoring with patient self-reporting of symptoms. However, this test is not available everywhere, and there is no consensus on how to interpret the results.^1,5,6 If you strongly suspect the patient has GERD-related cough but it fails to improve with intense medical management, then refer to a specialist, as antireflux surgery may be required.

Cough-variant asthma

Cough is the only symptom of asthma in cough-variant asthma, in which the usual features of dyspnea and wheezing are absent.⁷ A methacholine challenge shows bronchial hyperresponsiveness, and asthma therapy resolves the cough.

Nonasthmatic eosinophilic bronchitis

It is important to distinguish asthma from nonasthmatic eosinophilic bronchitis,^7,8 an underdiagnosed condition. Both conditions respond equally well to treatment with inhaled or oral steroids. However, patients who have nonasthmatic eosinophilic bronchitis have normal results on spirometry and the methacholine challenge test. The diagnosis of nonasthmatic eosinophilic bronchitis is made if more than 3% of the nonsquamous cells in an induced sputum sample are eosinophils.

UNCOMMON CAUSES OF COUGH

The remaining 5% of cases of cough are caused by conditions that include bronchogenic carcinoma, chronic interstitial pneumonia, sarcoidosis, left ventricular dysfunction, use of ACE inhibitors, neurosensory cough, dynamic airway collapse, aspiration due to pharyngeal dysfunction, and psychogenic causes.¹

MULTIPLE CAUSES

Therapeutic trials will support the diagnosis. If more than one cause is suggested, start treatment in the order in which the abnormalities are discovered. If treatment is only partially successful, then pursue further causes and add to the existing treatment without stopping it.

Cough may have more than one cause, but in up to 98% of patients it can be successfully treated.

IMPORTANT POINTS

• Multiple causes of chronic cough can coexist.
• Therapeutic trials are part of the workup.
• Do not stop therapy if it is only partially successful: add to existing therapies
• Start the investigation with the most likely cause.
• Treatment is 84% to 98% successful.

To begin, obtain a clinical history, perform a physical examination, and order a chest radiograph.

In the history, look for exposure to environmental irritants such as tobacco smoke, allergens, or dust, or medications such as angiotensin-converting enzyme (ACE) inhibitors or oxymetazoline (Afrin). If a potential irritant is present, it should be avoided or stopped immediately.^1–3 If the cough improves partially or fully when exposure to the irritant is stopped, this supports a diagnosis of chronic bronchitis or, in the case of ACE inhibitors, ACE-inhibitor-induced cough. The character of the cough (eg, paroxysmal, loose, dry, or productive¹) has not been shown to be diagnostically useful or specific.

If the chest radiograph is abnormal, then the diagnostic inquiry should be guided by the abnormality. Abnormalities that cause cough include bronchogenic carcinoma, sarcoidosis, and bronchiectasis. If the radiograph is normal, then upper airway cough syndrome, asthma, gastroesophageal reflux disease (GERD), chronic bronchitis, or nonasthmatic eosinophilic bronchitis is more likely.

COMMON CAUSES OF CHRONIC COUGH

Chronic bronchitis

As noted above, a history of exposure to an irritant suggests this diagnosis.

Upper airway cough syndrome

Upper airway cough syndrome (formerly known as postnasal drip) is due to chronic upper respiratory tract irritation and hypersensitivity of cough receptors.^3,4 Sources of irritation vary and include sinusitis and any form of rhinitis: allergic and nonallergic, postinfectious, environmental irritant-induced, vasomotor, and drug-induced.

Patients complain of postnasal drip or frequent clearing of the throat. On physical examination one can see mucus in the oropharnyx or a cobblestone appearance. However, these symptoms and signs are not specific and may be absent.

A therapeutic trial is warranted, but be aware that different rhinitides respond to specific treatments:

• Histamine-mediated or allergic rhinitis will respond to allergen avoidance, new-generation antihistamines such as loratadine (Claritin), mast cell stabilizers such as cromolyn (Intal), and intranasal glucocorticoids such as fluticasone (Flovent).^4,5
• Nonhistamine-mediated rhinitides (the common cold and perennial nonallergic rhinitis) respond to older-generation antihistamines such as diphenhydramine (Benadryl) and decongestant combinations. If these cannot be used, intranasal glucocorticoids and ipratropium (Atrovent) are alternatives.
• Vasomotor rhinitis will respond to intranasal ipratropium 0.3% for 3 weeks and then as required.
• Postinfective rhinitis, ie, a cough that began as severe bronchitis, would warrant an antihistamine-decongestant combination.

With adequate treatment, the cough should improve after 1 to 2 weeks; if rhinosinus symptoms persist, consider bacterial sinusitis and obtain radiographs of the sinuses. If imaging shows mucosal thickening (> 5 mm) or an air-fluid level, treat with decongestants and antibiotics for 3 weeks.^1,4,5

 

 

Gastroesophageal reflux disease

GERD is another common cause of cough, and the most difficult to exclude.⁵ Look for a history of reflux or heartburn and positional coughing, and have a low threshold for beginning empiric therapy. Indeed, according to the 2006 American College of Chest Physicians Cough Guideline Committee,^5,6 should a patient arrive in your clinic with a chronic cough and a normal chest radiograph who does not smoke and is not on an ACE inhibitor, then you should start empiric reflux therapy. Begin with lifestyle changes, acid suppression, and prokinetics. The cough may take 1 to 2 months before it begins to improve, and even longer to resolve.

The gold standard for diagnosis is 24-hour pH and impedance monitoring with patient self-reporting of symptoms. However, this test is not available everywhere, and there is no consensus on how to interpret the results.^1,5,6 If you strongly suspect the patient has GERD-related cough but it fails to improve with intense medical management, then refer to a specialist, as antireflux surgery may be required.

Cough-variant asthma

Cough is the only symptom of asthma in cough-variant asthma, in which the usual features of dyspnea and wheezing are absent.⁷ A methacholine challenge shows bronchial hyperresponsiveness, and asthma therapy resolves the cough.

Nonasthmatic eosinophilic bronchitis

It is important to distinguish asthma from nonasthmatic eosinophilic bronchitis,^7,8 an underdiagnosed condition. Both conditions respond equally well to treatment with inhaled or oral steroids. However, patients who have nonasthmatic eosinophilic bronchitis have normal results on spirometry and the methacholine challenge test. The diagnosis of nonasthmatic eosinophilic bronchitis is made if more than 3% of the nonsquamous cells in an induced sputum sample are eosinophils.

UNCOMMON CAUSES OF COUGH

The remaining 5% of cases of cough are caused by conditions that include bronchogenic carcinoma, chronic interstitial pneumonia, sarcoidosis, left ventricular dysfunction, use of ACE inhibitors, neurosensory cough, dynamic airway collapse, aspiration due to pharyngeal dysfunction, and psychogenic causes.¹

MULTIPLE CAUSES

Therapeutic trials will support the diagnosis. If more than one cause is suggested, start treatment in the order in which the abnormalities are discovered. If treatment is only partially successful, then pursue further causes and add to the existing treatment without stopping it.

Cough may have more than one cause, but in up to 98% of patients it can be successfully treated.

IMPORTANT POINTS

• Multiple causes of chronic cough can coexist.
• Therapeutic trials are part of the workup.
• Do not stop therapy if it is only partially successful: add to existing therapies
• Start the investigation with the most likely cause.
• Treatment is 84% to 98% successful.

To begin, obtain a clinical history, perform a physical examination, and order a chest radiograph.

In the history, look for exposure to environmental irritants such as tobacco smoke, allergens, or dust, or medications such as angiotensin-converting enzyme (ACE) inhibitors or oxymetazoline (Afrin). If a potential irritant is present, it should be avoided or stopped immediately.^1–3 If the cough improves partially or fully when exposure to the irritant is stopped, this supports a diagnosis of chronic bronchitis or, in the case of ACE inhibitors, ACE-inhibitor-induced cough. The character of the cough (eg, paroxysmal, loose, dry, or productive¹) has not been shown to be diagnostically useful or specific.

If the chest radiograph is abnormal, then the diagnostic inquiry should be guided by the abnormality. Abnormalities that cause cough include bronchogenic carcinoma, sarcoidosis, and bronchiectasis. If the radiograph is normal, then upper airway cough syndrome, asthma, gastroesophageal reflux disease (GERD), chronic bronchitis, or nonasthmatic eosinophilic bronchitis is more likely.

COMMON CAUSES OF CHRONIC COUGH

Chronic bronchitis

As noted above, a history of exposure to an irritant suggests this diagnosis.

Upper airway cough syndrome

Upper airway cough syndrome (formerly known as postnasal drip) is due to chronic upper respiratory tract irritation and hypersensitivity of cough receptors.^3,4 Sources of irritation vary and include sinusitis and any form of rhinitis: allergic and nonallergic, postinfectious, environmental irritant-induced, vasomotor, and drug-induced.

Patients complain of postnasal drip or frequent clearing of the throat. On physical examination one can see mucus in the oropharnyx or a cobblestone appearance. However, these symptoms and signs are not specific and may be absent.

A therapeutic trial is warranted, but be aware that different rhinitides respond to specific treatments:

• Histamine-mediated or allergic rhinitis will respond to allergen avoidance, new-generation antihistamines such as loratadine (Claritin), mast cell stabilizers such as cromolyn (Intal), and intranasal glucocorticoids such as fluticasone (Flovent).^4,5
• Nonhistamine-mediated rhinitides (the common cold and perennial nonallergic rhinitis) respond to older-generation antihistamines such as diphenhydramine (Benadryl) and decongestant combinations. If these cannot be used, intranasal glucocorticoids and ipratropium (Atrovent) are alternatives.
• Vasomotor rhinitis will respond to intranasal ipratropium 0.3% for 3 weeks and then as required.
• Postinfective rhinitis, ie, a cough that began as severe bronchitis, would warrant an antihistamine-decongestant combination.

With adequate treatment, the cough should improve after 1 to 2 weeks; if rhinosinus symptoms persist, consider bacterial sinusitis and obtain radiographs of the sinuses. If imaging shows mucosal thickening (> 5 mm) or an air-fluid level, treat with decongestants and antibiotics for 3 weeks.^1,4,5

 

 

Gastroesophageal reflux disease

GERD is another common cause of cough, and the most difficult to exclude.⁵ Look for a history of reflux or heartburn and positional coughing, and have a low threshold for beginning empiric therapy. Indeed, according to the 2006 American College of Chest Physicians Cough Guideline Committee,^5,6 should a patient arrive in your clinic with a chronic cough and a normal chest radiograph who does not smoke and is not on an ACE inhibitor, then you should start empiric reflux therapy. Begin with lifestyle changes, acid suppression, and prokinetics. The cough may take 1 to 2 months before it begins to improve, and even longer to resolve.

The gold standard for diagnosis is 24-hour pH and impedance monitoring with patient self-reporting of symptoms. However, this test is not available everywhere, and there is no consensus on how to interpret the results.^1,5,6 If you strongly suspect the patient has GERD-related cough but it fails to improve with intense medical management, then refer to a specialist, as antireflux surgery may be required.

Cough-variant asthma

Cough is the only symptom of asthma in cough-variant asthma, in which the usual features of dyspnea and wheezing are absent.⁷ A methacholine challenge shows bronchial hyperresponsiveness, and asthma therapy resolves the cough.

Nonasthmatic eosinophilic bronchitis

It is important to distinguish asthma from nonasthmatic eosinophilic bronchitis,^7,8 an underdiagnosed condition. Both conditions respond equally well to treatment with inhaled or oral steroids. However, patients who have nonasthmatic eosinophilic bronchitis have normal results on spirometry and the methacholine challenge test. The diagnosis of nonasthmatic eosinophilic bronchitis is made if more than 3% of the nonsquamous cells in an induced sputum sample are eosinophils.

UNCOMMON CAUSES OF COUGH

The remaining 5% of cases of cough are caused by conditions that include bronchogenic carcinoma, chronic interstitial pneumonia, sarcoidosis, left ventricular dysfunction, use of ACE inhibitors, neurosensory cough, dynamic airway collapse, aspiration due to pharyngeal dysfunction, and psychogenic causes.¹

MULTIPLE CAUSES

Therapeutic trials will support the diagnosis. If more than one cause is suggested, start treatment in the order in which the abnormalities are discovered. If treatment is only partially successful, then pursue further causes and add to the existing treatment without stopping it.

Cough may have more than one cause, but in up to 98% of patients it can be successfully treated.

IMPORTANT POINTS

• Multiple causes of chronic cough can coexist.
• Therapeutic trials are part of the workup.
• Do not stop therapy if it is only partially successful: add to existing therapies
• Start the investigation with the most likely cause.
• Treatment is 84% to 98% successful.

In the early stages of acute respiratory distress syndrome (ARDS), multiple areas of the lung collapse, most often in the dependent regions. A factor involved in this process is the loss of functional surfactant, creating a condition in which alveolar units are unstable and prone to collapse due to unopposed surface tension. This situation, similar to that in premature infants, results in a reduced volume of aerated lung, intrapulmonary shunting, and, therefore, poor oxygenation.

The treatment of this alveolar collapse is lung reinflation (or “recruitment,” a term first used by Lachmann).¹ Gattinoni et al² showed that the percentage of recruitable lung could range from a negligible fraction to 50% or more.

There are various means of reopening injured lungs and keeping them open. The choice of recruitment maneuver is based on the individual patient and the ventilatory mode.³

In this article, we review airway pressure release ventilation (APRV), a mode of mechanical ventilation that may be useful in situations in which, due to ARDS, the lungs need to be recruited and held open. APRV was developed as a lung-protective mode, allowing recruitment while minimizing ventilator-induced lung injury.

BASIC PRINCIPLES OF PROTECTIVE VENTILATION

This curve has two inflection points between which its slope is steep, indicating greater compliance or elasticity. Below the lower inflection point, the alveoli may collapse; above the upper inflection point, the lung loses its elastic properties and the alveoli are overdistended. To protect the lungs, the challenge in mechanical ventilation is to keep the lungs between these two points throughout the respiratory cycle.

Avoiding lung collapse by using PEEP

During mechanical ventilation, the pressure in the lungs is lowest, and thus the alveoli are most prone to collapse, at the end of expiration.

We want to prevent the alveoli from collapsing with each expiration and reopening with each inspiration, as this cycle of opening and closing damages them (causing atelectrauma, ie, cyclical atelectasis).⁴ Preventing it prevents the release of inflammatory mediators and the perpetuation of lung injury (biotrauma).⁵

The solution is to apply positive end-expiratory pressure (PEEP), taking into account the value of the lower inflection point when setting the PEEP level.

Villar et al⁶ compared outcomes in an intervention group that received a PEEP level 2 cm H₂O above the lower inflection point plus low tidal volumes, and in a control group that received higher tidal volumes and low PEEP (5 cm H₂O). The study was stopped early, after significantly more patients had died in the control group than in the intervention group (53% vs 32%, P = .04).

Avoiding overdistention by keeping the tidal volume low

Tidal volumes that exceed the upper inflection point overstretch the lung and induce volutrauma, which can manifest as pneumothorax or pneumomediastinum, or both—the lungs rupture like a balloon. Also, overdistention produces liberation of inflammatory mediators in the blood (biotrauma). High tidal volumes should therefore be avoided or limited as much as possible.

The ARDS Network,⁷ in a multicenter, randomized, controlled trial, showed that fewer patients die if they receive mechanical ventilation with low tidal volumes rather than higher, “conventional” tidal volumes. Patients were randomized to receive either a tidal volume of 6 mL/kg and a plateau pressure lower than 30 cm H₂O or a tidal volume of 12 mL/kg and a plateau pressure lower than 50 cm H₂O. They were followed for 180 days or until discharged home, breathing without assistance. A total of 861 patients were enrolled. The mortality rate was significantly lower in the low tidal volume group than in the group with conventional tidal volumes, 31% vs 40%.

Lower tidal volumes were also associated with faster attenuation of the inflammatory response.⁸

Amato et al⁹ randomized 58 patients to receive mechanical ventilation with tidal volumes of either 6 mL/kg or 12 mL/kg. The PEEP level was maintained above the lower inflection point. At 28 days, 62% of the patients in the intervention group were still alive, compared with only 29% in the control group. However, many concerns were expressed over the high mortality rate in the control group.

Based on these studies, the use of low tidal volumes with appropriate levels of PEEP to ensure lung recruitment is the current standard of care in mechanical ventilation of patients with ARDS.¹⁰

APRV: A PRESSURE-CONTROLLED MODE THAT ALLOWS SPONTANEOUS BREATHS

Reprinted from Frawley PM, Habashi NM. Airway pressure release ventilation: theory and practice. AACN Clinical Issues 2001; 12:234–246, with permission from Wolters Kluwer Health/Lippincott, Williams & Wilkins.

A baseline high pressure (P high) is set first. Mandatory breaths are achieved by releasing the high baseline pressure in the circuit very briefly, usually to 0 cm H₂O (P low), which allows the lungs to partially deflate, and then quickly resuming the high pressure before the unstable alveoli can collapse.

In theory, the optimal release time (the very short time in low pressure, or T low) in APRV should be determined by the time constant of the expiratory flow. The time constant (t) is the time it takes to empty 63% of the lung volume. It is calculated as:

t = C × R

where C is the combined compliance of the lung and chest wall, and R is the combined resistance of the endotracheal tube and the natural airways. In diseases that lead to lower lung compliance (such as ARDS), the time constant is shorter. A practical equilibrium time—or the time it takes for the lung volume in expiration to reach steady state (no expiratory flow)—is about 4 time constants.¹⁴

Since the release time in APRV is much shorter than the equilibrium time, a residual volume of air remains in the lung, creating intentional auto-PEEP. Ideally, this intentional auto-PEEP should be high enough to avoid derecruitment (optimally above the lower inflection point). In APRV the auto-PEEP is controlled by the settings, and this intentional restriction of the expiratory flow is critical to avoid derecruitment of unstable alveolar units.

The amount of time spent at the higher pressure (T high) is generally 80% to 95% of the cycle (ie, the lungs are “inflated” 80% to 95% of the time), and the amount of time at the lower pressure (T low) is 0.6 to 0.8 seconds.

Thus, APRV settings provide a relatively high mean airway pressure, which prevents collapse of unstable alveoli and over time recruits additional alveolar units in the injured lung. The major difference between this mode and more conventional modes is that in APRV the mean inspiratory pressure is maximized and end-expiratory pressure is due to intentional auto-PEEP. In addition, spontaneous breathing is allowed throughout the entire cycle (Figure 2).¹³

Although APRV does not approximate the physiology of spontaneous breathing with healthy lungs, it is nonetheless relatively comfortable and well tolerated. Its theoretical advantage in patients with lung injury is its ability to maximize alveoli recruitment by maintaining a higher mean inspiratory pressure, while the peak alveolar pressure remains lower than with conventional ventilation (Figure 1).

Other modes that are similar to APRV

Other modes of mechanical ventilation very similar to APRV are biphasic positive airway pressure (BiPAP) and bilevel ventilation.

BiPAP differs from APRV only in the timing of the upper and lower pressure levels. In BiPAP, T high is usually shorter than T low. Therefore, in order to avoid derecruitment, P low has to be set above zero with both a high and a low PEEP level.¹³

No studies have demonstrated one mode to be more beneficial than the other, although BiPAP might be more predictable, as both pressures are known.

Bilevel ventilation works like APRV but incorporates pressure support to spontaneous breathing. The use of pressure support may affect the positive physiologic effects (see section below) of unsupported spontaneous breathing. Nevertheless, this strategy might be useful to address severe hypercapnia in the context of APRV.

INITIAL VENTILATOR SETTINGS IN APRV

P high. In selecting an initial P high, we measure the plateau pressure in a conventional mode using an accepted protective strategy, such as volume-control mode. If the plateau pressure is lower than 30 cm H₂O, we use this pressure as our initial P high. If the plateau pressure is higher than 30 cm H₂O, we select 30 cm H₂O as an initial P high to minimize peak alveolar pressure and reduce the risk of lung overdistention.

P low is set at 0 cm H₂O.

T high is set at 4 seconds and is then adjusted if necessary.

T low is probably the most difficult variable to set because it needs to be short enough to avoid derecruitment but still long enough to allow alveolar ventilation. We usually start with a T low of 0.6 to 0.8 seconds.

ADJUSTING THE VENTILATOR SETTINGS

For hypoxemia. Physician-controlled variables that affect oxygenation in APRV are:

• Mean airway pressure (dependent primarily on P high and T high)
• Fraction of inspired oxygen (Fio₂).

Inadequate oxygenation usually requires increasing one or both of these settings.

Physician-controlled variables that affect alveolar ventilation in the APRV mode are:

• Pressure gradient (P high minus P low)
• Airway pressure release time (T low)
• Airway pressure release frequency.¹⁴ Frequency is related to total cycle time of mandatory breaths by the following equation³:

frequency = 60/cycle time = 60/(T high + T low).

Note that if T low remains constant, adjusting T high will adjust frequency (the more time the lung remains inflated, the lower the respiratory frequency). Conversely, some ventilators allow adjustment of frequency, making T high the dependent variable. The goal of this mode is to recruit alveoli and improve oxygenation, so we usually do not modify the pressure gradient to improve ventilation.

Reprinted from Frawley PM, Habashi NM. Airway pressure release ventilation: theory and practice. AACN Clinical Issues 2001; 12:234–246, with permission from Wolters Kluwer Health/Lippincott, Williams & Wilkins.

For hypercapnia. A frequent and expected consequence of lung-protective ventilation strategies is hypercapnia, termed “permissive” hypercapnia because it is allowed to some extent. In APRV, some degree of CO₂ retention is not unusual. When the measured Paco₂ becomes extreme, we usually increase the frequency of releases by shortening T high, recognizing that this adjustment may affect recruitment by lowering the mean airway pressure.

Spontaneous breaths. A positive aspect of APRV that contributes to its tolerability for patients is that it allows for spontaneous respiration. In some studies of patients with ARDS ventilated with APRV, spontaneous breathing accounted for 10% to 30% of the total minute ventilation and was responsible for an improvement in ventilation-perfusion matching and oxygenation.^15,16 We titrate our patients’ sedation to a goal of spontaneous breathing of at least 10% of total minute ventilation.

WEANING FROM APRV

Weaning from APRV is done carefully to avoid derecruitment. Some authors recommend lowering P high by 2 to 3 cm H₂O at a time and lengthening T high by increments of 0.5 to 2.0 seconds.^13,17

Once P high is about 16 cm H₂O, T high is at 12 to 15 seconds, and spontaneous respiration accounts for most or all of the minute volume, the mode can be changed to continuous positive airway pressure (CPAP) and titrated downwards. Usually, when CPAP is at 5 to 10 cm H₂O, the patient is extubated, provided that mental status or concerns about airway protection or secretions are not contraindications.

PHYSIOLOGIC EFFECTS OF APRV WITH SPONTANEOUS BREATHING

Effects on the respiratory system

During spontaneous breathing, the greatest displacement of the diaphragm is in dependent regions. These regions are the best ventilated.¹⁸ Compared with spontaneously breathing patients, mechanically ventilated patients have a smaller inspiratory displacement of the dependent part of the lung.¹⁹

A study using computed tomography demonstrated that the reduction of lung volume observed in patients with acute lung injury (ALI) predominantly affects the lower lobes (dependent areas).²⁰ Causative mechanisms could be an increase in lung weight related to ALI and a passive collapse of the lower lobes associated with an upward shift of the diaphragm.

In a preliminary study, the topographic distribution of lung collapse was different in spontaneously breathing ARDS patients than in patients who were paralyzed. In particular, lung densities were not concentrated in the dependent regions in the former group.²¹

Oxygenation is better with APRV with spontaneous breathing than with mechanical ventilation alone. This effect is at least partly attributable to recruitment of collapsed lung tissue and increased aeration of the dependent areas of the lung.²²

Putensen et al¹⁵ compared ventilation-perfusion distribution in 24 patients with ARDS who were randomized to APRV with spontaneous breathing (more than 10% of the total minute ventilation), APRV without spontaneous breathing, or pressure-support ventilation. Spontaneous breathing during APRV improved ventilation-perfusion matching and increased systemic blood flow.

Neumann et al²³ recently compared the effect of APRV with spontaneous breathing vs APRV without spontaneous breathing in terms of ventilation perfusion in an animal model of lung injury. APRV with spontaneous breathing increased ventilation in juxta-diaphragmatic regions, predominantly in dependent areas. Spontaneous breathing had a significant effect on the spatial distribution of ventilation and pulmonary perfusion.

Based on these studies, we generally use APRV with no pressure support. This strategy permits recruitment and expansion of dependent lung areas.

Effects on the cardiovascular system and hemodynamics

Räsänen et al,²⁴ in an animal model, compared cardiovascular performance during APRV, spontaneous breathing, and continuous positive pressure ventilation. No significant differences in cardiovascular function were detected between APRV and spontaneous breathing. In contrast, continuous positive pressure ventilation decreased blood pressure, stroke volume, cardiac output, and oxygen delivery.

Falkenhain et al,²⁵ in a subsequent case report, found that a change in mode from intermittent mandatory ventilation with PEEP to APRV resulted in improvement in the cardiac output of a patient requiring mechanical ventilation.

The lack of deleterious effect of APRV on cardiovascular function is probably a result of its spontaneous breathing component. The reduction in mean intrathoracic pressure during spontaneous breathing (compared to paralysis) improves venous return and biventricular filling, boosting cardiac output and oxygen delivery.²⁶

Hering et al²⁷ compared APRV with spontaneous breathing (at least 30% of the total minute ventilation) vs APRV with no spontaneous breathing in 12 patients with ALI. This study showed higher renal blood flow, glomerular filtration, and osmolar clearance in the APRV-with-spontaneous-breathing group.

The same investigators evaluated the effects of spontaneous breathing with APRV on intestinal blood flow in an animal model of lung injury.²⁸ Spontaneous breathing with APRV improved arterial oxygenation, the systemic hemodynamic profile, and regional perfusion to the stomach and small bowel compared with full ventilatory support.

ANIMAL STUDIES OF APRV

Stock et al,¹¹ in their original description of APRV in 1987, reported experimental results in dogs. In that study, 10 dogs with and without ARDS were randomized to APRV with a custom-built device vs volume-control mode with a Harvard pump ventilator plus PEEP. APRV delivered adequate alveolar ventilation, had lower peak airway pressures, and promoted better arterial oxygenation (at the same tidal volume and mean airway pressure) compared with volume control.

Martin et al (1991)²⁹ studied seven neonatal lambs with ALI with four ventilatory modes: pressure-support ventilation, APRV, volume control, and spontaneous breathing. APRV maintained oxygenation while augmenting alveolar ventilation compared with pressure-support ventilation. APRV also provided ventilation at a lower peak pressure in contrast to volume control. The authors concluded that APRV was an effective mode to maintain oxygenation and assist alveolar ventilation with minimal cardiovascular impact in their animal model of ALI.

HUMAN STUDIES OF APRV

Garner et al (1988)³⁰ studied 14 patients after operative coronary revascularization, giving them volume control mode (12 mL/kg) and then, when they were hemodynamically stable, APRV. While APRV and volume control supported ventilation and arterial oxygenation equally in all cases, peak airway pressure was greater with volume control.

Räsänen et al (1991)³¹ designed a prospective, multicenter, crossover trial in which 50 patients with ALI were ventilated with conventional ventilation and subsequently with APRV. Patients in both groups were adequately ventilated and oxygenated. However, as described in the aforementioned study,²⁴ the peak airway pressure was lower in the APRV group.

Davis et al (1993)³² studied 15 patients with ARDS requiring ventilatory support who received intermittent mandatory ventilation plus PEEP and then were placed on APRV. Peak airway pressure was lower, but mean airway pressure was higher with APRV. There were no statistically significant differences in gas exchange or hemodynamic variables.

Putensen et al,³³ in a study designed on the basis of prior publications,¹⁵ randomized 30 patients with multiple trauma to either APRV with spontaneous breathing (n = 15) or pressure-control ventilation (n = 15) for 72 hours. Weaning was performed with APRV in both groups. APRV was associated with increases in lung compliance and oxygenation and reduction of shunting. Interestingly, the use of APRV was associated with shorter duration of ventilatory support (15 vs 21 days), shorter length of intensive care unit stay (23 vs 30 days), and shorter duration of sedation and use of vasopressors.

An important confounder in this trial was that all patients on pressure-control ventilation were initially paralyzed, favoring the APRV group.

Varpula and colleagues³⁴ performed a prospective randomized intervention study to determine whether the response of oxygenation to the prone position differed between APRV vs pressure-controlled synchronized intermittent mandatory ventilation with pressure support. Forty-five patients with ALI were randomized within 72 hours of initiation of mechanical ventilation to receive one of these two modes; 33 ultimately received the assigned treatment. All patients were positioned on their stomachs for 6 hours once or twice a day. The response in terms of oxygenation to the first pronation was similar in both groups, whereas there was a significant improvement after the second pronation in the APRV group. The authors concluded that prone positioning and allowance of spontaneous breathing during APRV had advantageous effects on gas exchange.

In 2004, the same investigators³⁵ randomized 58 patients with ALI after stabilization to either APRV or pressure-controlled synchronized intermittent mandatory ventilation. There were no significant differences in the clinically important outcomes such as ventilator-free days, sedation days, need of hemodialysis, or intensive care unit-free days.

Dart et al,³⁶ in a retrospective study of 46 trauma patients who were ventilated with APRV for 72 hours, found an improvement in the Pao₂/Fio₂ ratio and a decrement in peak airway pressure after APRV was started.

Table 2 summarizes the randomized clinical trials of APRV.^33–35,37

CONCERNS ABOUT APRV

Overstretching. One of the major concerns when applying APRV is overstretching the lung parenchyma.^26,38 It is important to recognize that, when choosing a P high setting, this variable is not the only determinant of the tidal volume. Spontaneous breathing causes the pleural pressure to become less positive. As a result, there is an increase in the transpulmonary pressure (pressure in alveoli minus pressure in the pleura). This augmentation of transpulmonary pressure will result in a higher tidal volume and the risk of overdistention and volume-induced lung injury.

Atelectrauma. As mentioned earlier, damage may occur when airways open and close with each tidal cycle. This is particularly worrisome when the end-expiratory pressure is below the lower inflection point, as some diseased alveolar units may collapse. In APRV, the airway pressure is released to zero. Even though the intentional auto-PEEP might maintain a certain end-expiratory pressure, this parameter is truly uncontrolled.³⁹

If the patient cannot breath spontaneously. Another consideration is that many of the benefits of APRV are based on the spontaneous breathing component. Unfortunately, patients who need heavy sedation or neuromuscular paralysis with lack of spontaneous breathing efforts may lose the physiologic advantages of this mode.

Despite these limitations, APRV presents many attractive benefits as an alternative mode of mechanical ventilation in patients who do not respond to conventional modes.

Table 3 summarizes the advantages and disadvantages of each component of APRV.

In the early stages of acute respiratory distress syndrome (ARDS), multiple areas of the lung collapse, most often in the dependent regions. A factor involved in this process is the loss of functional surfactant, creating a condition in which alveolar units are unstable and prone to collapse due to unopposed surface tension. This situation, similar to that in premature infants, results in a reduced volume of aerated lung, intrapulmonary shunting, and, therefore, poor oxygenation.

The treatment of this alveolar collapse is lung reinflation (or “recruitment,” a term first used by Lachmann).¹ Gattinoni et al² showed that the percentage of recruitable lung could range from a negligible fraction to 50% or more.

There are various means of reopening injured lungs and keeping them open. The choice of recruitment maneuver is based on the individual patient and the ventilatory mode.³

In this article, we review airway pressure release ventilation (APRV), a mode of mechanical ventilation that may be useful in situations in which, due to ARDS, the lungs need to be recruited and held open. APRV was developed as a lung-protective mode, allowing recruitment while minimizing ventilator-induced lung injury.

BASIC PRINCIPLES OF PROTECTIVE VENTILATION

This curve has two inflection points between which its slope is steep, indicating greater compliance or elasticity. Below the lower inflection point, the alveoli may collapse; above the upper inflection point, the lung loses its elastic properties and the alveoli are overdistended. To protect the lungs, the challenge in mechanical ventilation is to keep the lungs between these two points throughout the respiratory cycle.

Avoiding lung collapse by using PEEP

During mechanical ventilation, the pressure in the lungs is lowest, and thus the alveoli are most prone to collapse, at the end of expiration.

We want to prevent the alveoli from collapsing with each expiration and reopening with each inspiration, as this cycle of opening and closing damages them (causing atelectrauma, ie, cyclical atelectasis).⁴ Preventing it prevents the release of inflammatory mediators and the perpetuation of lung injury (biotrauma).⁵

The solution is to apply positive end-expiratory pressure (PEEP), taking into account the value of the lower inflection point when setting the PEEP level.

Villar et al⁶ compared outcomes in an intervention group that received a PEEP level 2 cm H₂O above the lower inflection point plus low tidal volumes, and in a control group that received higher tidal volumes and low PEEP (5 cm H₂O). The study was stopped early, after significantly more patients had died in the control group than in the intervention group (53% vs 32%, P = .04).

Avoiding overdistention by keeping the tidal volume low

Tidal volumes that exceed the upper inflection point overstretch the lung and induce volutrauma, which can manifest as pneumothorax or pneumomediastinum, or both—the lungs rupture like a balloon. Also, overdistention produces liberation of inflammatory mediators in the blood (biotrauma). High tidal volumes should therefore be avoided or limited as much as possible.

The ARDS Network,⁷ in a multicenter, randomized, controlled trial, showed that fewer patients die if they receive mechanical ventilation with low tidal volumes rather than higher, “conventional” tidal volumes. Patients were randomized to receive either a tidal volume of 6 mL/kg and a plateau pressure lower than 30 cm H₂O or a tidal volume of 12 mL/kg and a plateau pressure lower than 50 cm H₂O. They were followed for 180 days or until discharged home, breathing without assistance. A total of 861 patients were enrolled. The mortality rate was significantly lower in the low tidal volume group than in the group with conventional tidal volumes, 31% vs 40%.

Lower tidal volumes were also associated with faster attenuation of the inflammatory response.⁸

Amato et al⁹ randomized 58 patients to receive mechanical ventilation with tidal volumes of either 6 mL/kg or 12 mL/kg. The PEEP level was maintained above the lower inflection point. At 28 days, 62% of the patients in the intervention group were still alive, compared with only 29% in the control group. However, many concerns were expressed over the high mortality rate in the control group.

Based on these studies, the use of low tidal volumes with appropriate levels of PEEP to ensure lung recruitment is the current standard of care in mechanical ventilation of patients with ARDS.¹⁰

APRV: A PRESSURE-CONTROLLED MODE THAT ALLOWS SPONTANEOUS BREATHS

Reprinted from Frawley PM, Habashi NM. Airway pressure release ventilation: theory and practice. AACN Clinical Issues 2001; 12:234–246, with permission from Wolters Kluwer Health/Lippincott, Williams & Wilkins.

A baseline high pressure (P high) is set first. Mandatory breaths are achieved by releasing the high baseline pressure in the circuit very briefly, usually to 0 cm H₂O (P low), which allows the lungs to partially deflate, and then quickly resuming the high pressure before the unstable alveoli can collapse.

In theory, the optimal release time (the very short time in low pressure, or T low) in APRV should be determined by the time constant of the expiratory flow. The time constant (t) is the time it takes to empty 63% of the lung volume. It is calculated as:

t = C × R

where C is the combined compliance of the lung and chest wall, and R is the combined resistance of the endotracheal tube and the natural airways. In diseases that lead to lower lung compliance (such as ARDS), the time constant is shorter. A practical equilibrium time—or the time it takes for the lung volume in expiration to reach steady state (no expiratory flow)—is about 4 time constants.¹⁴

Since the release time in APRV is much shorter than the equilibrium time, a residual volume of air remains in the lung, creating intentional auto-PEEP. Ideally, this intentional auto-PEEP should be high enough to avoid derecruitment (optimally above the lower inflection point). In APRV the auto-PEEP is controlled by the settings, and this intentional restriction of the expiratory flow is critical to avoid derecruitment of unstable alveolar units.

The amount of time spent at the higher pressure (T high) is generally 80% to 95% of the cycle (ie, the lungs are “inflated” 80% to 95% of the time), and the amount of time at the lower pressure (T low) is 0.6 to 0.8 seconds.

Thus, APRV settings provide a relatively high mean airway pressure, which prevents collapse of unstable alveoli and over time recruits additional alveolar units in the injured lung. The major difference between this mode and more conventional modes is that in APRV the mean inspiratory pressure is maximized and end-expiratory pressure is due to intentional auto-PEEP. In addition, spontaneous breathing is allowed throughout the entire cycle (Figure 2).¹³

Although APRV does not approximate the physiology of spontaneous breathing with healthy lungs, it is nonetheless relatively comfortable and well tolerated. Its theoretical advantage in patients with lung injury is its ability to maximize alveoli recruitment by maintaining a higher mean inspiratory pressure, while the peak alveolar pressure remains lower than with conventional ventilation (Figure 1).

Other modes that are similar to APRV

Other modes of mechanical ventilation very similar to APRV are biphasic positive airway pressure (BiPAP) and bilevel ventilation.

BiPAP differs from APRV only in the timing of the upper and lower pressure levels. In BiPAP, T high is usually shorter than T low. Therefore, in order to avoid derecruitment, P low has to be set above zero with both a high and a low PEEP level.¹³

No studies have demonstrated one mode to be more beneficial than the other, although BiPAP might be more predictable, as both pressures are known.

Bilevel ventilation works like APRV but incorporates pressure support to spontaneous breathing. The use of pressure support may affect the positive physiologic effects (see section below) of unsupported spontaneous breathing. Nevertheless, this strategy might be useful to address severe hypercapnia in the context of APRV.

INITIAL VENTILATOR SETTINGS IN APRV

P high. In selecting an initial P high, we measure the plateau pressure in a conventional mode using an accepted protective strategy, such as volume-control mode. If the plateau pressure is lower than 30 cm H₂O, we use this pressure as our initial P high. If the plateau pressure is higher than 30 cm H₂O, we select 30 cm H₂O as an initial P high to minimize peak alveolar pressure and reduce the risk of lung overdistention.

P low is set at 0 cm H₂O.

T high is set at 4 seconds and is then adjusted if necessary.

T low is probably the most difficult variable to set because it needs to be short enough to avoid derecruitment but still long enough to allow alveolar ventilation. We usually start with a T low of 0.6 to 0.8 seconds.

ADJUSTING THE VENTILATOR SETTINGS

For hypoxemia. Physician-controlled variables that affect oxygenation in APRV are:

• Mean airway pressure (dependent primarily on P high and T high)
• Fraction of inspired oxygen (Fio₂).

Inadequate oxygenation usually requires increasing one or both of these settings.

Physician-controlled variables that affect alveolar ventilation in the APRV mode are:

• Pressure gradient (P high minus P low)
• Airway pressure release time (T low)
• Airway pressure release frequency.¹⁴ Frequency is related to total cycle time of mandatory breaths by the following equation³:

frequency = 60/cycle time = 60/(T high + T low).

Note that if T low remains constant, adjusting T high will adjust frequency (the more time the lung remains inflated, the lower the respiratory frequency). Conversely, some ventilators allow adjustment of frequency, making T high the dependent variable. The goal of this mode is to recruit alveoli and improve oxygenation, so we usually do not modify the pressure gradient to improve ventilation.

Reprinted from Frawley PM, Habashi NM. Airway pressure release ventilation: theory and practice. AACN Clinical Issues 2001; 12:234–246, with permission from Wolters Kluwer Health/Lippincott, Williams & Wilkins.

For hypercapnia. A frequent and expected consequence of lung-protective ventilation strategies is hypercapnia, termed “permissive” hypercapnia because it is allowed to some extent. In APRV, some degree of CO₂ retention is not unusual. When the measured Paco₂ becomes extreme, we usually increase the frequency of releases by shortening T high, recognizing that this adjustment may affect recruitment by lowering the mean airway pressure.

Spontaneous breaths. A positive aspect of APRV that contributes to its tolerability for patients is that it allows for spontaneous respiration. In some studies of patients with ARDS ventilated with APRV, spontaneous breathing accounted for 10% to 30% of the total minute ventilation and was responsible for an improvement in ventilation-perfusion matching and oxygenation.^15,16 We titrate our patients’ sedation to a goal of spontaneous breathing of at least 10% of total minute ventilation.

WEANING FROM APRV

Weaning from APRV is done carefully to avoid derecruitment. Some authors recommend lowering P high by 2 to 3 cm H₂O at a time and lengthening T high by increments of 0.5 to 2.0 seconds.^13,17

Once P high is about 16 cm H₂O, T high is at 12 to 15 seconds, and spontaneous respiration accounts for most or all of the minute volume, the mode can be changed to continuous positive airway pressure (CPAP) and titrated downwards. Usually, when CPAP is at 5 to 10 cm H₂O, the patient is extubated, provided that mental status or concerns about airway protection or secretions are not contraindications.

PHYSIOLOGIC EFFECTS OF APRV WITH SPONTANEOUS BREATHING

Effects on the respiratory system

During spontaneous breathing, the greatest displacement of the diaphragm is in dependent regions. These regions are the best ventilated.¹⁸ Compared with spontaneously breathing patients, mechanically ventilated patients have a smaller inspiratory displacement of the dependent part of the lung.¹⁹

A study using computed tomography demonstrated that the reduction of lung volume observed in patients with acute lung injury (ALI) predominantly affects the lower lobes (dependent areas).²⁰ Causative mechanisms could be an increase in lung weight related to ALI and a passive collapse of the lower lobes associated with an upward shift of the diaphragm.

In a preliminary study, the topographic distribution of lung collapse was different in spontaneously breathing ARDS patients than in patients who were paralyzed. In particular, lung densities were not concentrated in the dependent regions in the former group.²¹

Oxygenation is better with APRV with spontaneous breathing than with mechanical ventilation alone. This effect is at least partly attributable to recruitment of collapsed lung tissue and increased aeration of the dependent areas of the lung.²²

Putensen et al¹⁵ compared ventilation-perfusion distribution in 24 patients with ARDS who were randomized to APRV with spontaneous breathing (more than 10% of the total minute ventilation), APRV without spontaneous breathing, or pressure-support ventilation. Spontaneous breathing during APRV improved ventilation-perfusion matching and increased systemic blood flow.

Neumann et al²³ recently compared the effect of APRV with spontaneous breathing vs APRV without spontaneous breathing in terms of ventilation perfusion in an animal model of lung injury. APRV with spontaneous breathing increased ventilation in juxta-diaphragmatic regions, predominantly in dependent areas. Spontaneous breathing had a significant effect on the spatial distribution of ventilation and pulmonary perfusion.

Based on these studies, we generally use APRV with no pressure support. This strategy permits recruitment and expansion of dependent lung areas.

Effects on the cardiovascular system and hemodynamics

Räsänen et al,²⁴ in an animal model, compared cardiovascular performance during APRV, spontaneous breathing, and continuous positive pressure ventilation. No significant differences in cardiovascular function were detected between APRV and spontaneous breathing. In contrast, continuous positive pressure ventilation decreased blood pressure, stroke volume, cardiac output, and oxygen delivery.

Falkenhain et al,²⁵ in a subsequent case report, found that a change in mode from intermittent mandatory ventilation with PEEP to APRV resulted in improvement in the cardiac output of a patient requiring mechanical ventilation.

The lack of deleterious effect of APRV on cardiovascular function is probably a result of its spontaneous breathing component. The reduction in mean intrathoracic pressure during spontaneous breathing (compared to paralysis) improves venous return and biventricular filling, boosting cardiac output and oxygen delivery.²⁶

Hering et al²⁷ compared APRV with spontaneous breathing (at least 30% of the total minute ventilation) vs APRV with no spontaneous breathing in 12 patients with ALI. This study showed higher renal blood flow, glomerular filtration, and osmolar clearance in the APRV-with-spontaneous-breathing group.

The same investigators evaluated the effects of spontaneous breathing with APRV on intestinal blood flow in an animal model of lung injury.²⁸ Spontaneous breathing with APRV improved arterial oxygenation, the systemic hemodynamic profile, and regional perfusion to the stomach and small bowel compared with full ventilatory support.

ANIMAL STUDIES OF APRV

Stock et al,¹¹ in their original description of APRV in 1987, reported experimental results in dogs. In that study, 10 dogs with and without ARDS were randomized to APRV with a custom-built device vs volume-control mode with a Harvard pump ventilator plus PEEP. APRV delivered adequate alveolar ventilation, had lower peak airway pressures, and promoted better arterial oxygenation (at the same tidal volume and mean airway pressure) compared with volume control.

Martin et al (1991)²⁹ studied seven neonatal lambs with ALI with four ventilatory modes: pressure-support ventilation, APRV, volume control, and spontaneous breathing. APRV maintained oxygenation while augmenting alveolar ventilation compared with pressure-support ventilation. APRV also provided ventilation at a lower peak pressure in contrast to volume control. The authors concluded that APRV was an effective mode to maintain oxygenation and assist alveolar ventilation with minimal cardiovascular impact in their animal model of ALI.

HUMAN STUDIES OF APRV

Garner et al (1988)³⁰ studied 14 patients after operative coronary revascularization, giving them volume control mode (12 mL/kg) and then, when they were hemodynamically stable, APRV. While APRV and volume control supported ventilation and arterial oxygenation equally in all cases, peak airway pressure was greater with volume control.

Räsänen et al (1991)³¹ designed a prospective, multicenter, crossover trial in which 50 patients with ALI were ventilated with conventional ventilation and subsequently with APRV. Patients in both groups were adequately ventilated and oxygenated. However, as described in the aforementioned study,²⁴ the peak airway pressure was lower in the APRV group.

Davis et al (1993)³² studied 15 patients with ARDS requiring ventilatory support who received intermittent mandatory ventilation plus PEEP and then were placed on APRV. Peak airway pressure was lower, but mean airway pressure was higher with APRV. There were no statistically significant differences in gas exchange or hemodynamic variables.

Putensen et al,³³ in a study designed on the basis of prior publications,¹⁵ randomized 30 patients with multiple trauma to either APRV with spontaneous breathing (n = 15) or pressure-control ventilation (n = 15) for 72 hours. Weaning was performed with APRV in both groups. APRV was associated with increases in lung compliance and oxygenation and reduction of shunting. Interestingly, the use of APRV was associated with shorter duration of ventilatory support (15 vs 21 days), shorter length of intensive care unit stay (23 vs 30 days), and shorter duration of sedation and use of vasopressors.

An important confounder in this trial was that all patients on pressure-control ventilation were initially paralyzed, favoring the APRV group.

Varpula and colleagues³⁴ performed a prospective randomized intervention study to determine whether the response of oxygenation to the prone position differed between APRV vs pressure-controlled synchronized intermittent mandatory ventilation with pressure support. Forty-five patients with ALI were randomized within 72 hours of initiation of mechanical ventilation to receive one of these two modes; 33 ultimately received the assigned treatment. All patients were positioned on their stomachs for 6 hours once or twice a day. The response in terms of oxygenation to the first pronation was similar in both groups, whereas there was a significant improvement after the second pronation in the APRV group. The authors concluded that prone positioning and allowance of spontaneous breathing during APRV had advantageous effects on gas exchange.

In 2004, the same investigators³⁵ randomized 58 patients with ALI after stabilization to either APRV or pressure-controlled synchronized intermittent mandatory ventilation. There were no significant differences in the clinically important outcomes such as ventilator-free days, sedation days, need of hemodialysis, or intensive care unit-free days.

Dart et al,³⁶ in a retrospective study of 46 trauma patients who were ventilated with APRV for 72 hours, found an improvement in the Pao₂/Fio₂ ratio and a decrement in peak airway pressure after APRV was started.

Table 2 summarizes the randomized clinical trials of APRV.^33–35,37

CONCERNS ABOUT APRV

Overstretching. One of the major concerns when applying APRV is overstretching the lung parenchyma.^26,38 It is important to recognize that, when choosing a P high setting, this variable is not the only determinant of the tidal volume. Spontaneous breathing causes the pleural pressure to become less positive. As a result, there is an increase in the transpulmonary pressure (pressure in alveoli minus pressure in the pleura). This augmentation of transpulmonary pressure will result in a higher tidal volume and the risk of overdistention and volume-induced lung injury.

Atelectrauma. As mentioned earlier, damage may occur when airways open and close with each tidal cycle. This is particularly worrisome when the end-expiratory pressure is below the lower inflection point, as some diseased alveolar units may collapse. In APRV, the airway pressure is released to zero. Even though the intentional auto-PEEP might maintain a certain end-expiratory pressure, this parameter is truly uncontrolled.³⁹

If the patient cannot breath spontaneously. Another consideration is that many of the benefits of APRV are based on the spontaneous breathing component. Unfortunately, patients who need heavy sedation or neuromuscular paralysis with lack of spontaneous breathing efforts may lose the physiologic advantages of this mode.

Despite these limitations, APRV presents many attractive benefits as an alternative mode of mechanical ventilation in patients who do not respond to conventional modes.

Table 3 summarizes the advantages and disadvantages of each component of APRV.

In the early stages of acute respiratory distress syndrome (ARDS), multiple areas of the lung collapse, most often in the dependent regions. A factor involved in this process is the loss of functional surfactant, creating a condition in which alveolar units are unstable and prone to collapse due to unopposed surface tension. This situation, similar to that in premature infants, results in a reduced volume of aerated lung, intrapulmonary shunting, and, therefore, poor oxygenation.

The treatment of this alveolar collapse is lung reinflation (or “recruitment,” a term first used by Lachmann).¹ Gattinoni et al² showed that the percentage of recruitable lung could range from a negligible fraction to 50% or more.

There are various means of reopening injured lungs and keeping them open. The choice of recruitment maneuver is based on the individual patient and the ventilatory mode.³

In this article, we review airway pressure release ventilation (APRV), a mode of mechanical ventilation that may be useful in situations in which, due to ARDS, the lungs need to be recruited and held open. APRV was developed as a lung-protective mode, allowing recruitment while minimizing ventilator-induced lung injury.

BASIC PRINCIPLES OF PROTECTIVE VENTILATION

This curve has two inflection points between which its slope is steep, indicating greater compliance or elasticity. Below the lower inflection point, the alveoli may collapse; above the upper inflection point, the lung loses its elastic properties and the alveoli are overdistended. To protect the lungs, the challenge in mechanical ventilation is to keep the lungs between these two points throughout the respiratory cycle.

Avoiding lung collapse by using PEEP

During mechanical ventilation, the pressure in the lungs is lowest, and thus the alveoli are most prone to collapse, at the end of expiration.

We want to prevent the alveoli from collapsing with each expiration and reopening with each inspiration, as this cycle of opening and closing damages them (causing atelectrauma, ie, cyclical atelectasis).⁴ Preventing it prevents the release of inflammatory mediators and the perpetuation of lung injury (biotrauma).⁵

The solution is to apply positive end-expiratory pressure (PEEP), taking into account the value of the lower inflection point when setting the PEEP level.

Villar et al⁶ compared outcomes in an intervention group that received a PEEP level 2 cm H₂O above the lower inflection point plus low tidal volumes, and in a control group that received higher tidal volumes and low PEEP (5 cm H₂O). The study was stopped early, after significantly more patients had died in the control group than in the intervention group (53% vs 32%, P = .04).

Avoiding overdistention by keeping the tidal volume low

Tidal volumes that exceed the upper inflection point overstretch the lung and induce volutrauma, which can manifest as pneumothorax or pneumomediastinum, or both—the lungs rupture like a balloon. Also, overdistention produces liberation of inflammatory mediators in the blood (biotrauma). High tidal volumes should therefore be avoided or limited as much as possible.

The ARDS Network,⁷ in a multicenter, randomized, controlled trial, showed that fewer patients die if they receive mechanical ventilation with low tidal volumes rather than higher, “conventional” tidal volumes. Patients were randomized to receive either a tidal volume of 6 mL/kg and a plateau pressure lower than 30 cm H₂O or a tidal volume of 12 mL/kg and a plateau pressure lower than 50 cm H₂O. They were followed for 180 days or until discharged home, breathing without assistance. A total of 861 patients were enrolled. The mortality rate was significantly lower in the low tidal volume group than in the group with conventional tidal volumes, 31% vs 40%.

Lower tidal volumes were also associated with faster attenuation of the inflammatory response.⁸

Amato et al⁹ randomized 58 patients to receive mechanical ventilation with tidal volumes of either 6 mL/kg or 12 mL/kg. The PEEP level was maintained above the lower inflection point. At 28 days, 62% of the patients in the intervention group were still alive, compared with only 29% in the control group. However, many concerns were expressed over the high mortality rate in the control group.

Based on these studies, the use of low tidal volumes with appropriate levels of PEEP to ensure lung recruitment is the current standard of care in mechanical ventilation of patients with ARDS.¹⁰

APRV: A PRESSURE-CONTROLLED MODE THAT ALLOWS SPONTANEOUS BREATHS

Reprinted from Frawley PM, Habashi NM. Airway pressure release ventilation: theory and practice. AACN Clinical Issues 2001; 12:234–246, with permission from Wolters Kluwer Health/Lippincott, Williams & Wilkins.

A baseline high pressure (P high) is set first. Mandatory breaths are achieved by releasing the high baseline pressure in the circuit very briefly, usually to 0 cm H₂O (P low), which allows the lungs to partially deflate, and then quickly resuming the high pressure before the unstable alveoli can collapse.

In theory, the optimal release time (the very short time in low pressure, or T low) in APRV should be determined by the time constant of the expiratory flow. The time constant (t) is the time it takes to empty 63% of the lung volume. It is calculated as:

t = C × R

where C is the combined compliance of the lung and chest wall, and R is the combined resistance of the endotracheal tube and the natural airways. In diseases that lead to lower lung compliance (such as ARDS), the time constant is shorter. A practical equilibrium time—or the time it takes for the lung volume in expiration to reach steady state (no expiratory flow)—is about 4 time constants.¹⁴

Since the release time in APRV is much shorter than the equilibrium time, a residual volume of air remains in the lung, creating intentional auto-PEEP. Ideally, this intentional auto-PEEP should be high enough to avoid derecruitment (optimally above the lower inflection point). In APRV the auto-PEEP is controlled by the settings, and this intentional restriction of the expiratory flow is critical to avoid derecruitment of unstable alveolar units.

The amount of time spent at the higher pressure (T high) is generally 80% to 95% of the cycle (ie, the lungs are “inflated” 80% to 95% of the time), and the amount of time at the lower pressure (T low) is 0.6 to 0.8 seconds.

Thus, APRV settings provide a relatively high mean airway pressure, which prevents collapse of unstable alveoli and over time recruits additional alveolar units in the injured lung. The major difference between this mode and more conventional modes is that in APRV the mean inspiratory pressure is maximized and end-expiratory pressure is due to intentional auto-PEEP. In addition, spontaneous breathing is allowed throughout the entire cycle (Figure 2).¹³

Although APRV does not approximate the physiology of spontaneous breathing with healthy lungs, it is nonetheless relatively comfortable and well tolerated. Its theoretical advantage in patients with lung injury is its ability to maximize alveoli recruitment by maintaining a higher mean inspiratory pressure, while the peak alveolar pressure remains lower than with conventional ventilation (Figure 1).

Other modes that are similar to APRV

Other modes of mechanical ventilation very similar to APRV are biphasic positive airway pressure (BiPAP) and bilevel ventilation.

BiPAP differs from APRV only in the timing of the upper and lower pressure levels. In BiPAP, T high is usually shorter than T low. Therefore, in order to avoid derecruitment, P low has to be set above zero with both a high and a low PEEP level.¹³

No studies have demonstrated one mode to be more beneficial than the other, although BiPAP might be more predictable, as both pressures are known.

Bilevel ventilation works like APRV but incorporates pressure support to spontaneous breathing. The use of pressure support may affect the positive physiologic effects (see section below) of unsupported spontaneous breathing. Nevertheless, this strategy might be useful to address severe hypercapnia in the context of APRV.

INITIAL VENTILATOR SETTINGS IN APRV

P high. In selecting an initial P high, we measure the plateau pressure in a conventional mode using an accepted protective strategy, such as volume-control mode. If the plateau pressure is lower than 30 cm H₂O, we use this pressure as our initial P high. If the plateau pressure is higher than 30 cm H₂O, we select 30 cm H₂O as an initial P high to minimize peak alveolar pressure and reduce the risk of lung overdistention.

P low is set at 0 cm H₂O.

T high is set at 4 seconds and is then adjusted if necessary.

T low is probably the most difficult variable to set because it needs to be short enough to avoid derecruitment but still long enough to allow alveolar ventilation. We usually start with a T low of 0.6 to 0.8 seconds.

ADJUSTING THE VENTILATOR SETTINGS

For hypoxemia. Physician-controlled variables that affect oxygenation in APRV are:

• Mean airway pressure (dependent primarily on P high and T high)
• Fraction of inspired oxygen (Fio₂).

Inadequate oxygenation usually requires increasing one or both of these settings.

Physician-controlled variables that affect alveolar ventilation in the APRV mode are:

• Pressure gradient (P high minus P low)
• Airway pressure release time (T low)
• Airway pressure release frequency.¹⁴ Frequency is related to total cycle time of mandatory breaths by the following equation³:

frequency = 60/cycle time = 60/(T high + T low).

Note that if T low remains constant, adjusting T high will adjust frequency (the more time the lung remains inflated, the lower the respiratory frequency). Conversely, some ventilators allow adjustment of frequency, making T high the dependent variable. The goal of this mode is to recruit alveoli and improve oxygenation, so we usually do not modify the pressure gradient to improve ventilation.

Reprinted from Frawley PM, Habashi NM. Airway pressure release ventilation: theory and practice. AACN Clinical Issues 2001; 12:234–246, with permission from Wolters Kluwer Health/Lippincott, Williams & Wilkins.

For hypercapnia. A frequent and expected consequence of lung-protective ventilation strategies is hypercapnia, termed “permissive” hypercapnia because it is allowed to some extent. In APRV, some degree of CO₂ retention is not unusual. When the measured Paco₂ becomes extreme, we usually increase the frequency of releases by shortening T high, recognizing that this adjustment may affect recruitment by lowering the mean airway pressure.

Spontaneous breaths. A positive aspect of APRV that contributes to its tolerability for patients is that it allows for spontaneous respiration. In some studies of patients with ARDS ventilated with APRV, spontaneous breathing accounted for 10% to 30% of the total minute ventilation and was responsible for an improvement in ventilation-perfusion matching and oxygenation.^15,16 We titrate our patients’ sedation to a goal of spontaneous breathing of at least 10% of total minute ventilation.

WEANING FROM APRV

Weaning from APRV is done carefully to avoid derecruitment. Some authors recommend lowering P high by 2 to 3 cm H₂O at a time and lengthening T high by increments of 0.5 to 2.0 seconds.^13,17

Once P high is about 16 cm H₂O, T high is at 12 to 15 seconds, and spontaneous respiration accounts for most or all of the minute volume, the mode can be changed to continuous positive airway pressure (CPAP) and titrated downwards. Usually, when CPAP is at 5 to 10 cm H₂O, the patient is extubated, provided that mental status or concerns about airway protection or secretions are not contraindications.

PHYSIOLOGIC EFFECTS OF APRV WITH SPONTANEOUS BREATHING

Effects on the respiratory system

During spontaneous breathing, the greatest displacement of the diaphragm is in dependent regions. These regions are the best ventilated.¹⁸ Compared with spontaneously breathing patients, mechanically ventilated patients have a smaller inspiratory displacement of the dependent part of the lung.¹⁹

A study using computed tomography demonstrated that the reduction of lung volume observed in patients with acute lung injury (ALI) predominantly affects the lower lobes (dependent areas).²⁰ Causative mechanisms could be an increase in lung weight related to ALI and a passive collapse of the lower lobes associated with an upward shift of the diaphragm.

In a preliminary study, the topographic distribution of lung collapse was different in spontaneously breathing ARDS patients than in patients who were paralyzed. In particular, lung densities were not concentrated in the dependent regions in the former group.²¹

Oxygenation is better with APRV with spontaneous breathing than with mechanical ventilation alone. This effect is at least partly attributable to recruitment of collapsed lung tissue and increased aeration of the dependent areas of the lung.²²

Putensen et al¹⁵ compared ventilation-perfusion distribution in 24 patients with ARDS who were randomized to APRV with spontaneous breathing (more than 10% of the total minute ventilation), APRV without spontaneous breathing, or pressure-support ventilation. Spontaneous breathing during APRV improved ventilation-perfusion matching and increased systemic blood flow.

Neumann et al²³ recently compared the effect of APRV with spontaneous breathing vs APRV without spontaneous breathing in terms of ventilation perfusion in an animal model of lung injury. APRV with spontaneous breathing increased ventilation in juxta-diaphragmatic regions, predominantly in dependent areas. Spontaneous breathing had a significant effect on the spatial distribution of ventilation and pulmonary perfusion.

Based on these studies, we generally use APRV with no pressure support. This strategy permits recruitment and expansion of dependent lung areas.

Effects on the cardiovascular system and hemodynamics

Räsänen et al,²⁴ in an animal model, compared cardiovascular performance during APRV, spontaneous breathing, and continuous positive pressure ventilation. No significant differences in cardiovascular function were detected between APRV and spontaneous breathing. In contrast, continuous positive pressure ventilation decreased blood pressure, stroke volume, cardiac output, and oxygen delivery.

Falkenhain et al,²⁵ in a subsequent case report, found that a change in mode from intermittent mandatory ventilation with PEEP to APRV resulted in improvement in the cardiac output of a patient requiring mechanical ventilation.

The lack of deleterious effect of APRV on cardiovascular function is probably a result of its spontaneous breathing component. The reduction in mean intrathoracic pressure during spontaneous breathing (compared to paralysis) improves venous return and biventricular filling, boosting cardiac output and oxygen delivery.²⁶

Hering et al²⁷ compared APRV with spontaneous breathing (at least 30% of the total minute ventilation) vs APRV with no spontaneous breathing in 12 patients with ALI. This study showed higher renal blood flow, glomerular filtration, and osmolar clearance in the APRV-with-spontaneous-breathing group.

The same investigators evaluated the effects of spontaneous breathing with APRV on intestinal blood flow in an animal model of lung injury.²⁸ Spontaneous breathing with APRV improved arterial oxygenation, the systemic hemodynamic profile, and regional perfusion to the stomach and small bowel compared with full ventilatory support.

ANIMAL STUDIES OF APRV

Stock et al,¹¹ in their original description of APRV in 1987, reported experimental results in dogs. In that study, 10 dogs with and without ARDS were randomized to APRV with a custom-built device vs volume-control mode with a Harvard pump ventilator plus PEEP. APRV delivered adequate alveolar ventilation, had lower peak airway pressures, and promoted better arterial oxygenation (at the same tidal volume and mean airway pressure) compared with volume control.

Martin et al (1991)²⁹ studied seven neonatal lambs with ALI with four ventilatory modes: pressure-support ventilation, APRV, volume control, and spontaneous breathing. APRV maintained oxygenation while augmenting alveolar ventilation compared with pressure-support ventilation. APRV also provided ventilation at a lower peak pressure in contrast to volume control. The authors concluded that APRV was an effective mode to maintain oxygenation and assist alveolar ventilation with minimal cardiovascular impact in their animal model of ALI.

HUMAN STUDIES OF APRV

Garner et al (1988)³⁰ studied 14 patients after operative coronary revascularization, giving them volume control mode (12 mL/kg) and then, when they were hemodynamically stable, APRV. While APRV and volume control supported ventilation and arterial oxygenation equally in all cases, peak airway pressure was greater with volume control.

Räsänen et al (1991)³¹ designed a prospective, multicenter, crossover trial in which 50 patients with ALI were ventilated with conventional ventilation and subsequently with APRV. Patients in both groups were adequately ventilated and oxygenated. However, as described in the aforementioned study,²⁴ the peak airway pressure was lower in the APRV group.

Davis et al (1993)³² studied 15 patients with ARDS requiring ventilatory support who received intermittent mandatory ventilation plus PEEP and then were placed on APRV. Peak airway pressure was lower, but mean airway pressure was higher with APRV. There were no statistically significant differences in gas exchange or hemodynamic variables.

Putensen et al,³³ in a study designed on the basis of prior publications,¹⁵ randomized 30 patients with multiple trauma to either APRV with spontaneous breathing (n = 15) or pressure-control ventilation (n = 15) for 72 hours. Weaning was performed with APRV in both groups. APRV was associated with increases in lung compliance and oxygenation and reduction of shunting. Interestingly, the use of APRV was associated with shorter duration of ventilatory support (15 vs 21 days), shorter length of intensive care unit stay (23 vs 30 days), and shorter duration of sedation and use of vasopressors.

An important confounder in this trial was that all patients on pressure-control ventilation were initially paralyzed, favoring the APRV group.

Varpula and colleagues³⁴ performed a prospective randomized intervention study to determine whether the response of oxygenation to the prone position differed between APRV vs pressure-controlled synchronized intermittent mandatory ventilation with pressure support. Forty-five patients with ALI were randomized within 72 hours of initiation of mechanical ventilation to receive one of these two modes; 33 ultimately received the assigned treatment. All patients were positioned on their stomachs for 6 hours once or twice a day. The response in terms of oxygenation to the first pronation was similar in both groups, whereas there was a significant improvement after the second pronation in the APRV group. The authors concluded that prone positioning and allowance of spontaneous breathing during APRV had advantageous effects on gas exchange.

In 2004, the same investigators³⁵ randomized 58 patients with ALI after stabilization to either APRV or pressure-controlled synchronized intermittent mandatory ventilation. There were no significant differences in the clinically important outcomes such as ventilator-free days, sedation days, need of hemodialysis, or intensive care unit-free days.

Dart et al,³⁶ in a retrospective study of 46 trauma patients who were ventilated with APRV for 72 hours, found an improvement in the Pao₂/Fio₂ ratio and a decrement in peak airway pressure after APRV was started.

Table 2 summarizes the randomized clinical trials of APRV.^33–35,37

CONCERNS ABOUT APRV

Overstretching. One of the major concerns when applying APRV is overstretching the lung parenchyma.^26,38 It is important to recognize that, when choosing a P high setting, this variable is not the only determinant of the tidal volume. Spontaneous breathing causes the pleural pressure to become less positive. As a result, there is an increase in the transpulmonary pressure (pressure in alveoli minus pressure in the pleura). This augmentation of transpulmonary pressure will result in a higher tidal volume and the risk of overdistention and volume-induced lung injury.

Atelectrauma. As mentioned earlier, damage may occur when airways open and close with each tidal cycle. This is particularly worrisome when the end-expiratory pressure is below the lower inflection point, as some diseased alveolar units may collapse. In APRV, the airway pressure is released to zero. Even though the intentional auto-PEEP might maintain a certain end-expiratory pressure, this parameter is truly uncontrolled.³⁹

If the patient cannot breath spontaneously. Another consideration is that many of the benefits of APRV are based on the spontaneous breathing component. Unfortunately, patients who need heavy sedation or neuromuscular paralysis with lack of spontaneous breathing efforts may lose the physiologic advantages of this mode.

Despite these limitations, APRV presents many attractive benefits as an alternative mode of mechanical ventilation in patients who do not respond to conventional modes.

Table 3 summarizes the advantages and disadvantages of each component of APRV.