NATIONAL HARBOR, Md.—As HM10 wound down in this tony Washington, D.C., outpost, a trio of hospitalists from St. Louis smiled widely and brightly as a stranger took their picture in front of the main stage.

Each raved about the quality of the meeting they had just completed, particularly the way it linked HM leaders from across the country to such ubiquitous problems as transitional care and patient falls found in institutions from Seattle to Cincinnati to South Carolina. And with a record 2,500 hospitalists attending SHM’s annual meeting this year, what better time to smile?

“Your world suddenly becomes much smaller because you can reach out to people, rather than feel like you’re lost in this massive machine,” said Lois Richard, MD, PhD, FHM, a hospitalist with Washington University Physicians at the Washington University School of Medicine in St. Louis.

Dr. Richard’s commentary on belonging to a larger scene is a fitting allegory for the state of HM, as the field has grown beyond its neophyte stage. Now that the field has swelled to an estimated 30,000 nationwide, SHM’s new president said the time has come to move past the adolescent phase. Jeff Wiese, MD, FACP, SFHM, associate professor of medicine at Tulane University Health Sciences Center in New Orleans, wants hospitalists to continue championing quality-improvement (QI) programs and patient-safety efforts.

“We’re at a stage as an organization that we need to continue to do the quality-education efforts, but we need to start rising to that next level, which is the quality execution and solutions,” he said during a keynote address, adding later that “we have great heterogeneity in the society. Some people are quality experts because they received great training from SHM, Intermountain Health, IHI, but then there are many members that are interested and really want to be that quality expert but are to the left on the continuum, still learning how to do it.”

The path to quality development began anew with the four-day meeting April 8-11 at the Gaylord National Resort & Convention Center on the banks of the Potomac River. The largest meeting in SHM history kicked off with its largest menu of pre-course sessions, designed to offer educational credits to CME-hungry physicians. This year’s choices included a pair of new sessions, one geared toward neurology and the other aimed at early-career hospitalists. The increased offerings worked, as SHM officials reported a preliminary pre-course attendance increase of 10% from last year’s meeting.

Another big draw for the meeting was the keynote address from Paul Levy, president and CEO of Beth Israel Deaconess Medical Center in Boston. Levy has quickly built himself a national platform to push for QI in the nation’s hospitals, along with public reporting and transparency. Levy said “we still do too much harm in our hospitals,” but wants to see that improved not because of radical changes in payment streams, but because of physicians who want to do better by their patients.

“Ignore the healthcare reform bill,” he said in his address. “Ignore all the fuss about it. Focus instead on the underlying values that you each have individually, and that you have collectively, as to why you became docs in the first place.”

The theme of quality and the future continued speaker after speaker, session after session. Meeting faculty used their microphones to expound on how the recently passed healthcare legislation does more to expand access to healthcare than change the current rules governing it. Most talked about the potential role hospitalists can play in the fluid landscape bound to develop in the next few years, with SHM CEO Larry Wellikson, MD, SFHM, going as far as to describe the field as “the rocketship moving upward almost to a limitless future.”

Still, the future only comes once the past has been recognized, and this year’s meeting will be remembered for the first three physicians who were honored as Masters in Hospital Medicine: John Nelson, Robert Wachter, and Winthrop Whitcomb. The latter described the ceremony as a moving experience for himself and his family.

“When John and I first started working on this in October 1996, and we had the first substantive conversation, I had a really strong feeling that this was going to be successful,” Dr. Whitcomb said. “I saw the forces gathering to drive this, but I definitely didn’t have any idea it was going to be this thing. I don’t think any of us did. . . . What we did want was to have a community.”

This year’s meeting continued to draw scores of first-timers looking to experience a bit of that community. Meeting attendance has nearly doubled since the 2008 meeting in San Diego, with a significant percentage of attendees falling into the early-career hospitalist category.

That includes physicians like Matthew Mechtenberg, DO, a hospitalist at Parkview Adventist Medical Center in Brunswick, Maine. A two-year hospitalist who formerly worked in private practice, he traveled to the meeting as part of his hospital’s focus on performance measures and QI. He was heartened to learn tricks of the trade—billing for encephalopathy instead of “altered mental status” might capture more costs for some patients—but just as importantly, it was comforting to know many of his institution’s problems are universal.

“Some of the issues I have in my hospital are the same as they have in Beth Israel Deaconess,” Dr. Mechtenberg said. “Issues translate whether you’re in a 50-bed hospital or an 800-bed hospital. That’s reassuring.”

And then there was Bihar Dianati, MD, a hospitalist at Belleville Memorial Hospital in Belleville, Ill., who previously couldn’t attend the annual meeting because he worked a Monday-Friday schedule. With his recent switch to “seven-on, seven-off,” he decided to use his week off for professional development.

Dr. Dianati bounced between sessions, finding some “self-promoting” but others “incredibly helpful.” But any professional meeting is only successful if it draws repeat business. So will Dr. Dianati be back next year for HM11 at the Gaylord Hotel in Grapevine, Texas?

“Oh, definitely,” Dr. Dianati said. “I already took the registration papers for next year.” HM10

Richard Quinn is a freelance writer based in New Jersey.

NATIONAL HARBOR, Md.—As HM10 wound down in this tony Washington, D.C., outpost, a trio of hospitalists from St. Louis smiled widely and brightly as a stranger took their picture in front of the main stage.

Each raved about the quality of the meeting they had just completed, particularly the way it linked HM leaders from across the country to such ubiquitous problems as transitional care and patient falls found in institutions from Seattle to Cincinnati to South Carolina. And with a record 2,500 hospitalists attending SHM’s annual meeting this year, what better time to smile?

“Your world suddenly becomes much smaller because you can reach out to people, rather than feel like you’re lost in this massive machine,” said Lois Richard, MD, PhD, FHM, a hospitalist with Washington University Physicians at the Washington University School of Medicine in St. Louis.

Dr. Richard’s commentary on belonging to a larger scene is a fitting allegory for the state of HM, as the field has grown beyond its neophyte stage. Now that the field has swelled to an estimated 30,000 nationwide, SHM’s new president said the time has come to move past the adolescent phase. Jeff Wiese, MD, FACP, SFHM, associate professor of medicine at Tulane University Health Sciences Center in New Orleans, wants hospitalists to continue championing quality-improvement (QI) programs and patient-safety efforts.

“We’re at a stage as an organization that we need to continue to do the quality-education efforts, but we need to start rising to that next level, which is the quality execution and solutions,” he said during a keynote address, adding later that “we have great heterogeneity in the society. Some people are quality experts because they received great training from SHM, Intermountain Health, IHI, but then there are many members that are interested and really want to be that quality expert but are to the left on the continuum, still learning how to do it.”

The path to quality development began anew with the four-day meeting April 8-11 at the Gaylord National Resort & Convention Center on the banks of the Potomac River. The largest meeting in SHM history kicked off with its largest menu of pre-course sessions, designed to offer educational credits to CME-hungry physicians. This year’s choices included a pair of new sessions, one geared toward neurology and the other aimed at early-career hospitalists. The increased offerings worked, as SHM officials reported a preliminary pre-course attendance increase of 10% from last year’s meeting.

Another big draw for the meeting was the keynote address from Paul Levy, president and CEO of Beth Israel Deaconess Medical Center in Boston. Levy has quickly built himself a national platform to push for QI in the nation’s hospitals, along with public reporting and transparency. Levy said “we still do too much harm in our hospitals,” but wants to see that improved not because of radical changes in payment streams, but because of physicians who want to do better by their patients.

“Ignore the healthcare reform bill,” he said in his address. “Ignore all the fuss about it. Focus instead on the underlying values that you each have individually, and that you have collectively, as to why you became docs in the first place.”

The theme of quality and the future continued speaker after speaker, session after session. Meeting faculty used their microphones to expound on how the recently passed healthcare legislation does more to expand access to healthcare than change the current rules governing it. Most talked about the potential role hospitalists can play in the fluid landscape bound to develop in the next few years, with SHM CEO Larry Wellikson, MD, SFHM, going as far as to describe the field as “the rocketship moving upward almost to a limitless future.”

Still, the future only comes once the past has been recognized, and this year’s meeting will be remembered for the first three physicians who were honored as Masters in Hospital Medicine: John Nelson, Robert Wachter, and Winthrop Whitcomb. The latter described the ceremony as a moving experience for himself and his family.

“When John and I first started working on this in October 1996, and we had the first substantive conversation, I had a really strong feeling that this was going to be successful,” Dr. Whitcomb said. “I saw the forces gathering to drive this, but I definitely didn’t have any idea it was going to be this thing. I don’t think any of us did. . . . What we did want was to have a community.”

This year’s meeting continued to draw scores of first-timers looking to experience a bit of that community. Meeting attendance has nearly doubled since the 2008 meeting in San Diego, with a significant percentage of attendees falling into the early-career hospitalist category.

That includes physicians like Matthew Mechtenberg, DO, a hospitalist at Parkview Adventist Medical Center in Brunswick, Maine. A two-year hospitalist who formerly worked in private practice, he traveled to the meeting as part of his hospital’s focus on performance measures and QI. He was heartened to learn tricks of the trade—billing for encephalopathy instead of “altered mental status” might capture more costs for some patients—but just as importantly, it was comforting to know many of his institution’s problems are universal.

“Some of the issues I have in my hospital are the same as they have in Beth Israel Deaconess,” Dr. Mechtenberg said. “Issues translate whether you’re in a 50-bed hospital or an 800-bed hospital. That’s reassuring.”

And then there was Bihar Dianati, MD, a hospitalist at Belleville Memorial Hospital in Belleville, Ill., who previously couldn’t attend the annual meeting because he worked a Monday-Friday schedule. With his recent switch to “seven-on, seven-off,” he decided to use his week off for professional development.

Dr. Dianati bounced between sessions, finding some “self-promoting” but others “incredibly helpful.” But any professional meeting is only successful if it draws repeat business. So will Dr. Dianati be back next year for HM11 at the Gaylord Hotel in Grapevine, Texas?

“Oh, definitely,” Dr. Dianati said. “I already took the registration papers for next year.” HM10

Richard Quinn is a freelance writer based in New Jersey.

NATIONAL HARBOR, Md.—As HM10 wound down in this tony Washington, D.C., outpost, a trio of hospitalists from St. Louis smiled widely and brightly as a stranger took their picture in front of the main stage.

Each raved about the quality of the meeting they had just completed, particularly the way it linked HM leaders from across the country to such ubiquitous problems as transitional care and patient falls found in institutions from Seattle to Cincinnati to South Carolina. And with a record 2,500 hospitalists attending SHM’s annual meeting this year, what better time to smile?

“Your world suddenly becomes much smaller because you can reach out to people, rather than feel like you’re lost in this massive machine,” said Lois Richard, MD, PhD, FHM, a hospitalist with Washington University Physicians at the Washington University School of Medicine in St. Louis.

Dr. Richard’s commentary on belonging to a larger scene is a fitting allegory for the state of HM, as the field has grown beyond its neophyte stage. Now that the field has swelled to an estimated 30,000 nationwide, SHM’s new president said the time has come to move past the adolescent phase. Jeff Wiese, MD, FACP, SFHM, associate professor of medicine at Tulane University Health Sciences Center in New Orleans, wants hospitalists to continue championing quality-improvement (QI) programs and patient-safety efforts.

“We’re at a stage as an organization that we need to continue to do the quality-education efforts, but we need to start rising to that next level, which is the quality execution and solutions,” he said during a keynote address, adding later that “we have great heterogeneity in the society. Some people are quality experts because they received great training from SHM, Intermountain Health, IHI, but then there are many members that are interested and really want to be that quality expert but are to the left on the continuum, still learning how to do it.”

The path to quality development began anew with the four-day meeting April 8-11 at the Gaylord National Resort & Convention Center on the banks of the Potomac River. The largest meeting in SHM history kicked off with its largest menu of pre-course sessions, designed to offer educational credits to CME-hungry physicians. This year’s choices included a pair of new sessions, one geared toward neurology and the other aimed at early-career hospitalists. The increased offerings worked, as SHM officials reported a preliminary pre-course attendance increase of 10% from last year’s meeting.

Another big draw for the meeting was the keynote address from Paul Levy, president and CEO of Beth Israel Deaconess Medical Center in Boston. Levy has quickly built himself a national platform to push for QI in the nation’s hospitals, along with public reporting and transparency. Levy said “we still do too much harm in our hospitals,” but wants to see that improved not because of radical changes in payment streams, but because of physicians who want to do better by their patients.

“Ignore the healthcare reform bill,” he said in his address. “Ignore all the fuss about it. Focus instead on the underlying values that you each have individually, and that you have collectively, as to why you became docs in the first place.”

The theme of quality and the future continued speaker after speaker, session after session. Meeting faculty used their microphones to expound on how the recently passed healthcare legislation does more to expand access to healthcare than change the current rules governing it. Most talked about the potential role hospitalists can play in the fluid landscape bound to develop in the next few years, with SHM CEO Larry Wellikson, MD, SFHM, going as far as to describe the field as “the rocketship moving upward almost to a limitless future.”

Still, the future only comes once the past has been recognized, and this year’s meeting will be remembered for the first three physicians who were honored as Masters in Hospital Medicine: John Nelson, Robert Wachter, and Winthrop Whitcomb. The latter described the ceremony as a moving experience for himself and his family.

“When John and I first started working on this in October 1996, and we had the first substantive conversation, I had a really strong feeling that this was going to be successful,” Dr. Whitcomb said. “I saw the forces gathering to drive this, but I definitely didn’t have any idea it was going to be this thing. I don’t think any of us did. . . . What we did want was to have a community.”

This year’s meeting continued to draw scores of first-timers looking to experience a bit of that community. Meeting attendance has nearly doubled since the 2008 meeting in San Diego, with a significant percentage of attendees falling into the early-career hospitalist category.

That includes physicians like Matthew Mechtenberg, DO, a hospitalist at Parkview Adventist Medical Center in Brunswick, Maine. A two-year hospitalist who formerly worked in private practice, he traveled to the meeting as part of his hospital’s focus on performance measures and QI. He was heartened to learn tricks of the trade—billing for encephalopathy instead of “altered mental status” might capture more costs for some patients—but just as importantly, it was comforting to know many of his institution’s problems are universal.

“Some of the issues I have in my hospital are the same as they have in Beth Israel Deaconess,” Dr. Mechtenberg said. “Issues translate whether you’re in a 50-bed hospital or an 800-bed hospital. That’s reassuring.”

And then there was Bihar Dianati, MD, a hospitalist at Belleville Memorial Hospital in Belleville, Ill., who previously couldn’t attend the annual meeting because he worked a Monday-Friday schedule. With his recent switch to “seven-on, seven-off,” he decided to use his week off for professional development.

Dr. Dianati bounced between sessions, finding some “self-promoting” but others “incredibly helpful.” But any professional meeting is only successful if it draws repeat business. So will Dr. Dianati be back next year for HM11 at the Gaylord Hotel in Grapevine, Texas?

“Oh, definitely,” Dr. Dianati said. “I already took the registration papers for next year.” HM10

Richard Quinn is a freelance writer based in New Jersey.

NATIONAL HARBOR, Md.—;Amie Dlouhy, RN, BSN, hospitalist program manager with Saint Mary’s Health Care in Grand Rapids, Mich., couldn’t scribble notes furiously enough during the practice-management pre-course at HM10. Dlouhy was promoted to her new position as an administrator some six weeks before the annual meeting at the Gaylord National Resort & Convention Center in early April.

So the first-time meeting attendee decided she would jot down as many tips as she could. She quickly realized the trip was worth it, as she learned that a departmental dashboard is a relatively simple way to gather key information in one place. She also likes the idea of drawing up a brochure that tells patients what they can expect from their hospitalists—and perhaps vice versa. And what new HM group leader doesn’t want advice on building a schedule that adds individualized wrinkles to the “seven-on, seven-off” structure?

“It is a business and you need to treat it as if it’s a business,” Dlouhy said. “It’s an ongoing process, and you want to make sure you have a concrete foundation.”

The tidbits Dlouhy gleaned from her pre-course were among scores of nuggets discussed during eight of the accredited educational sessions. This year’s pre-courses boosted to a new high of 20 the number of Category 1 credits physicians could earn toward the American Medical Association’s (AMA) Physician Recognition Award. Last year, the total was 15.

Offering more classes—and more varied topics—worked pretty well, as this year’s slate of pre-courses was more popular than ever, according to SHM officials. At HM09 in Chicago, more than 800 attendees participated in six sessions. At HM10, the total attendance was roughly 10% higher.

A main driver of the growth was the addition of two new courses—“Essential Neurology for the Hospitalist” and “Early Career Hospitalist: Skills for Success.” Another was a packed room of hospitalists answering questions—some right, some wrong—and preparing for the new Focused Practice in Hospital Medicine (FPHM) via the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC). The learning session pre-course debuted last year, but the new HM pathway to board recertification helped push attendance higher this year.

“The nice thing about the audience-response system is that you can actually see that not everybody is always going straight to the right answer on all of the questions,” said Julius Yang, MD, PhD, a hospitalist at Beth Israel Deaconess Medical Center in Boston and the MOC course director. “It’s really serving as an important refresher of our medical knowledge base.”

Dr. Yang said the “mini-retreat” environment of an annual convention is the perfect place to focus on granular professional development. “Trying to do these types of MOCs when you’re working to keep current with all of your other duties, you don’t get as much out of it,” Dr. Yang said. “Here, you get it all.”

He adds that those physicians who take the time and spend the money to travel for an educational session tend to be very focused on taking advantage of the program, not just showing up to be counted.

“All of these [questions] are very much directed at growing as a hospitalist,” Dr. Yang said. “It’s a different focus than the rest of the meeting. This is about every individual bringing something back to their institution.”

That’s what keeps bringing Troy Ahlstrom, MD, FHM, back. Dr. Ahlstrom, of Hos-pitalists of Northwest Michigan in Traverse City, has been to three annual meetings, and he said he tries to hit a pre-course every time. Last year, it was a session on how to more completely capture costs from billing and coding.

This year: “Comprehensive Critical Care in 2010: An Interactive Course.” The former appealed to him given that every HM group needs to capture as many of its charges as possible, and the latter because his group helps staff the critical-care units of three hospitals.

Several physicians noted that the critical-care pre-course was particularly appealing to attendees, as more hospitalists are handling those duties at their respective institutions. The format was popular, too, and was structured in the same way as the ABIM learning session, with course director David Schul-man, MD, MPH, chief of pulmonary and critical-care medicine at Emory University Hospital in Atlanta, leading a room full of hospitalists through a multiple-choice exam.

Dr. Ahlstrom and others noted that aside from the engagement in education that the daylong pre-courses offer, the sessions are set up with take-home guides, reference materials, and earnest pledges for mentoring from speakers and SHM staff.

“Most medical meetings have a scientific focus with a couple of practical aspects,” Dr. Ahlstrom said. “SHM’s meeting is very practical. It presents research, but it’s research you will use in your practice.”

Gerald Johnson, MD, a hospitalist at Texoma Medical Center in Denison, Texas, signed up for the “Best Practices in Managing a Hospital Medicine Program” pre-course during his first visit to an SHM meeting. A hospitalist for about four years, Dr. Johnson decided to take the pre-course at the urging of senior colleagues. He said the most helpful lessons he gleaned were about compensation plans, scheduling, and staffing.

“It’s not one person getting up there and presenting ‘This is how it needs to be done,’ ” Dr. Johnson said. “They present you with several ways. It really gives you something to adapt to your personal environment.”

Dr. Johnson, who gushed about “the gurus” of HM leading his session, also likes the fact that people with both a financial pedigree and a background in clinical work present the information. In fact, several attendees of the best-practices session noted that the attention to both medicine and management helps fill in the gaps between being a clinician and being a businessman.

“You’ve got to do both well,” Dr. Ahlstrom said. “You’ve got to take good care of patients. But in order to take good care of patients, you have to run a good business model, too.” HM10

Richard Quinn is a freelance writer based in New Jersey.

NATIONAL HARBOR, Md.—;Amie Dlouhy, RN, BSN, hospitalist program manager with Saint Mary’s Health Care in Grand Rapids, Mich., couldn’t scribble notes furiously enough during the practice-management pre-course at HM10. Dlouhy was promoted to her new position as an administrator some six weeks before the annual meeting at the Gaylord National Resort & Convention Center in early April.

So the first-time meeting attendee decided she would jot down as many tips as she could. She quickly realized the trip was worth it, as she learned that a departmental dashboard is a relatively simple way to gather key information in one place. She also likes the idea of drawing up a brochure that tells patients what they can expect from their hospitalists—and perhaps vice versa. And what new HM group leader doesn’t want advice on building a schedule that adds individualized wrinkles to the “seven-on, seven-off” structure?

“It is a business and you need to treat it as if it’s a business,” Dlouhy said. “It’s an ongoing process, and you want to make sure you have a concrete foundation.”

The tidbits Dlouhy gleaned from her pre-course were among scores of nuggets discussed during eight of the accredited educational sessions. This year’s pre-courses boosted to a new high of 20 the number of Category 1 credits physicians could earn toward the American Medical Association’s (AMA) Physician Recognition Award. Last year, the total was 15.

Offering more classes—and more varied topics—worked pretty well, as this year’s slate of pre-courses was more popular than ever, according to SHM officials. At HM09 in Chicago, more than 800 attendees participated in six sessions. At HM10, the total attendance was roughly 10% higher.

A main driver of the growth was the addition of two new courses—“Essential Neurology for the Hospitalist” and “Early Career Hospitalist: Skills for Success.” Another was a packed room of hospitalists answering questions—some right, some wrong—and preparing for the new Focused Practice in Hospital Medicine (FPHM) via the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC). The learning session pre-course debuted last year, but the new HM pathway to board recertification helped push attendance higher this year.

“The nice thing about the audience-response system is that you can actually see that not everybody is always going straight to the right answer on all of the questions,” said Julius Yang, MD, PhD, a hospitalist at Beth Israel Deaconess Medical Center in Boston and the MOC course director. “It’s really serving as an important refresher of our medical knowledge base.”

Dr. Yang said the “mini-retreat” environment of an annual convention is the perfect place to focus on granular professional development. “Trying to do these types of MOCs when you’re working to keep current with all of your other duties, you don’t get as much out of it,” Dr. Yang said. “Here, you get it all.”

He adds that those physicians who take the time and spend the money to travel for an educational session tend to be very focused on taking advantage of the program, not just showing up to be counted.

“All of these [questions] are very much directed at growing as a hospitalist,” Dr. Yang said. “It’s a different focus than the rest of the meeting. This is about every individual bringing something back to their institution.”

That’s what keeps bringing Troy Ahlstrom, MD, FHM, back. Dr. Ahlstrom, of Hos-pitalists of Northwest Michigan in Traverse City, has been to three annual meetings, and he said he tries to hit a pre-course every time. Last year, it was a session on how to more completely capture costs from billing and coding.

This year: “Comprehensive Critical Care in 2010: An Interactive Course.” The former appealed to him given that every HM group needs to capture as many of its charges as possible, and the latter because his group helps staff the critical-care units of three hospitals.

Several physicians noted that the critical-care pre-course was particularly appealing to attendees, as more hospitalists are handling those duties at their respective institutions. The format was popular, too, and was structured in the same way as the ABIM learning session, with course director David Schul-man, MD, MPH, chief of pulmonary and critical-care medicine at Emory University Hospital in Atlanta, leading a room full of hospitalists through a multiple-choice exam.

Dr. Ahlstrom and others noted that aside from the engagement in education that the daylong pre-courses offer, the sessions are set up with take-home guides, reference materials, and earnest pledges for mentoring from speakers and SHM staff.

“Most medical meetings have a scientific focus with a couple of practical aspects,” Dr. Ahlstrom said. “SHM’s meeting is very practical. It presents research, but it’s research you will use in your practice.”

Gerald Johnson, MD, a hospitalist at Texoma Medical Center in Denison, Texas, signed up for the “Best Practices in Managing a Hospital Medicine Program” pre-course during his first visit to an SHM meeting. A hospitalist for about four years, Dr. Johnson decided to take the pre-course at the urging of senior colleagues. He said the most helpful lessons he gleaned were about compensation plans, scheduling, and staffing.

“It’s not one person getting up there and presenting ‘This is how it needs to be done,’ ” Dr. Johnson said. “They present you with several ways. It really gives you something to adapt to your personal environment.”

Dr. Johnson, who gushed about “the gurus” of HM leading his session, also likes the fact that people with both a financial pedigree and a background in clinical work present the information. In fact, several attendees of the best-practices session noted that the attention to both medicine and management helps fill in the gaps between being a clinician and being a businessman.

“You’ve got to do both well,” Dr. Ahlstrom said. “You’ve got to take good care of patients. But in order to take good care of patients, you have to run a good business model, too.” HM10

Richard Quinn is a freelance writer based in New Jersey.

NATIONAL HARBOR, Md.—;Amie Dlouhy, RN, BSN, hospitalist program manager with Saint Mary’s Health Care in Grand Rapids, Mich., couldn’t scribble notes furiously enough during the practice-management pre-course at HM10. Dlouhy was promoted to her new position as an administrator some six weeks before the annual meeting at the Gaylord National Resort & Convention Center in early April.

So the first-time meeting attendee decided she would jot down as many tips as she could. She quickly realized the trip was worth it, as she learned that a departmental dashboard is a relatively simple way to gather key information in one place. She also likes the idea of drawing up a brochure that tells patients what they can expect from their hospitalists—and perhaps vice versa. And what new HM group leader doesn’t want advice on building a schedule that adds individualized wrinkles to the “seven-on, seven-off” structure?

“It is a business and you need to treat it as if it’s a business,” Dlouhy said. “It’s an ongoing process, and you want to make sure you have a concrete foundation.”

The tidbits Dlouhy gleaned from her pre-course were among scores of nuggets discussed during eight of the accredited educational sessions. This year’s pre-courses boosted to a new high of 20 the number of Category 1 credits physicians could earn toward the American Medical Association’s (AMA) Physician Recognition Award. Last year, the total was 15.

Offering more classes—and more varied topics—worked pretty well, as this year’s slate of pre-courses was more popular than ever, according to SHM officials. At HM09 in Chicago, more than 800 attendees participated in six sessions. At HM10, the total attendance was roughly 10% higher.

A main driver of the growth was the addition of two new courses—“Essential Neurology for the Hospitalist” and “Early Career Hospitalist: Skills for Success.” Another was a packed room of hospitalists answering questions—some right, some wrong—and preparing for the new Focused Practice in Hospital Medicine (FPHM) via the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC). The learning session pre-course debuted last year, but the new HM pathway to board recertification helped push attendance higher this year.

“The nice thing about the audience-response system is that you can actually see that not everybody is always going straight to the right answer on all of the questions,” said Julius Yang, MD, PhD, a hospitalist at Beth Israel Deaconess Medical Center in Boston and the MOC course director. “It’s really serving as an important refresher of our medical knowledge base.”

Dr. Yang said the “mini-retreat” environment of an annual convention is the perfect place to focus on granular professional development. “Trying to do these types of MOCs when you’re working to keep current with all of your other duties, you don’t get as much out of it,” Dr. Yang said. “Here, you get it all.”

He adds that those physicians who take the time and spend the money to travel for an educational session tend to be very focused on taking advantage of the program, not just showing up to be counted.

“All of these [questions] are very much directed at growing as a hospitalist,” Dr. Yang said. “It’s a different focus than the rest of the meeting. This is about every individual bringing something back to their institution.”

That’s what keeps bringing Troy Ahlstrom, MD, FHM, back. Dr. Ahlstrom, of Hos-pitalists of Northwest Michigan in Traverse City, has been to three annual meetings, and he said he tries to hit a pre-course every time. Last year, it was a session on how to more completely capture costs from billing and coding.

This year: “Comprehensive Critical Care in 2010: An Interactive Course.” The former appealed to him given that every HM group needs to capture as many of its charges as possible, and the latter because his group helps staff the critical-care units of three hospitals.

Several physicians noted that the critical-care pre-course was particularly appealing to attendees, as more hospitalists are handling those duties at their respective institutions. The format was popular, too, and was structured in the same way as the ABIM learning session, with course director David Schul-man, MD, MPH, chief of pulmonary and critical-care medicine at Emory University Hospital in Atlanta, leading a room full of hospitalists through a multiple-choice exam.

Dr. Ahlstrom and others noted that aside from the engagement in education that the daylong pre-courses offer, the sessions are set up with take-home guides, reference materials, and earnest pledges for mentoring from speakers and SHM staff.

“Most medical meetings have a scientific focus with a couple of practical aspects,” Dr. Ahlstrom said. “SHM’s meeting is very practical. It presents research, but it’s research you will use in your practice.”

Gerald Johnson, MD, a hospitalist at Texoma Medical Center in Denison, Texas, signed up for the “Best Practices in Managing a Hospital Medicine Program” pre-course during his first visit to an SHM meeting. A hospitalist for about four years, Dr. Johnson decided to take the pre-course at the urging of senior colleagues. He said the most helpful lessons he gleaned were about compensation plans, scheduling, and staffing.

“It’s not one person getting up there and presenting ‘This is how it needs to be done,’ ” Dr. Johnson said. “They present you with several ways. It really gives you something to adapt to your personal environment.”

Dr. Johnson, who gushed about “the gurus” of HM leading his session, also likes the fact that people with both a financial pedigree and a background in clinical work present the information. In fact, several attendees of the best-practices session noted that the attention to both medicine and management helps fill in the gaps between being a clinician and being a businessman.

“You’ve got to do both well,” Dr. Ahlstrom said. “You’ve got to take good care of patients. But in order to take good care of patients, you have to run a good business model, too.” HM10

Richard Quinn is a freelance writer based in New Jersey.

“We are the champions.”

The emotion-triggering tune that blares nightly at sports stadiums across the country was pretty much a slogan at SHM’s annual meeting, held April 8-11 at the Gaylord National Resort & Convention Center in National Harbor, Md., just outside Washington, D.C.

From new SHM President Jeff Weise’s use of the lyric to analogize HM’s arrival as a force in healthcare reform to the Hall of Fame-tinged ceremony inducting the first three Masters in Hospital Medicine—John Nelson, Robert Wachter, and Winthrop Whitcomb—this once-a-year gathering is no longer about seeking respect as a specialty. It’s blossomed into a sold-out, four-day strategy session looking at various ways to improve the delivery of care to patients.

“What we say is going to be taken seriously,” said Dr. Wiese, MD, FACP, SFHM, associate professor of medicine at Tulane University Health Sciences Center in New Orleans. “Which means that it has to be the right message—which means that it has to be about patient care.” HM10

“We are the champions.”

The emotion-triggering tune that blares nightly at sports stadiums across the country was pretty much a slogan at SHM’s annual meeting, held April 8-11 at the Gaylord National Resort & Convention Center in National Harbor, Md., just outside Washington, D.C.

From new SHM President Jeff Weise’s use of the lyric to analogize HM’s arrival as a force in healthcare reform to the Hall of Fame-tinged ceremony inducting the first three Masters in Hospital Medicine—John Nelson, Robert Wachter, and Winthrop Whitcomb—this once-a-year gathering is no longer about seeking respect as a specialty. It’s blossomed into a sold-out, four-day strategy session looking at various ways to improve the delivery of care to patients.

“What we say is going to be taken seriously,” said Dr. Wiese, MD, FACP, SFHM, associate professor of medicine at Tulane University Health Sciences Center in New Orleans. “Which means that it has to be the right message—which means that it has to be about patient care.” HM10

“We are the champions.”

The emotion-triggering tune that blares nightly at sports stadiums across the country was pretty much a slogan at SHM’s annual meeting, held April 8-11 at the Gaylord National Resort & Convention Center in National Harbor, Md., just outside Washington, D.C.

From new SHM President Jeff Weise’s use of the lyric to analogize HM’s arrival as a force in healthcare reform to the Hall of Fame-tinged ceremony inducting the first three Masters in Hospital Medicine—John Nelson, Robert Wachter, and Winthrop Whitcomb—this once-a-year gathering is no longer about seeking respect as a specialty. It’s blossomed into a sold-out, four-day strategy session looking at various ways to improve the delivery of care to patients.

“What we say is going to be taken seriously,” said Dr. Wiese, MD, FACP, SFHM, associate professor of medicine at Tulane University Health Sciences Center in New Orleans. “Which means that it has to be the right message—which means that it has to be about patient care.” HM10

As the prevalence of type 2 diabetes mellitus (T2DM) rises, primary care physicians must be prepared to manage this disease. In this supplement, 5 key topics related to T2DM are discussed—obesity, postprandial glucose, diabetic peripheral neuropathic pain, dyslipidemia, and the incretins.

As the prevalence of type 2 diabetes mellitus (T2DM) rises, primary care physicians must be prepared to manage this disease. In this supplement, 5 key topics related to T2DM are discussed—obesity, postprandial glucose, diabetic peripheral neuropathic pain, dyslipidemia, and the incretins.

As the prevalence of type 2 diabetes mellitus (T2DM) rises, primary care physicians must be prepared to manage this disease. In this supplement, 5 key topics related to T2DM are discussed—obesity, postprandial glucose, diabetic peripheral neuropathic pain, dyslipidemia, and the incretins.

Noninvasive positive pressure ventilation (NIPPV)—delivered via a tight-fitting mask rather than via an endotracheal tube or tracheostomy—is one of the most important advances in the management of acute respiratory failure to emerge in the past 2 decades. It is now recommended as the first choice for ventilatory support in selected patients, such as those with exacerbations of chronic obstructive pulmonary disease (COPD) or with cardiogenic pulmonary edema.^1–3 In fact, some authors suggest that using NIPPV in more than 20% of COPD patients is a characteristic of respiratory care departments that are “avid for change”⁴—change being a good thing.

However, NIPPV has not been universally accepted, with wide variations in its utilization. In a 2006 survey, it was being used in only 33% of patients with COPD or congestive heart failure, for which it might be indicated. ⁵ Some potential reasons for the low rate are that physicians do not know about it, respiratory therapists are not sufficiently trained in it, and hospitals lack the equipment to do it.⁵

Our goal in this review is to familiarize the reader with how NIPPV has evolved and with its indications and contraindications in specific acute care conditions.

FROM A VACUUM CLEANER TO THE INTENSIVE CARE UNIT

NIPPV appears to have been first tried in 1870 by Chaussier, who used a bag and face mask to resuscitate neonates.⁶

In 1936, Poulton and Oxon⁷ described their “pulmonary plus pressure machine,” which used a vacuum cleaner blower and a mask to increase the alveolar pressure and thus counteract the increased intrapulmonary pressure in patients with heart failure, pulmonary edema, Cheyne-Stokes breathing, and asthma.

In the 1940s, intermittent positive pressure breathing devices were developed for use in high-altitude aviation. Motley, Werko, and Cournand^8,9 subsequently used these devices to treat acute respiratory failure in pneumonia, pulmonary edema, near-drowning, Guillain-Barré syndrome, and acute severe asthma.

Although NIPPV was shown to be effective for acute conditions, invasive ventilation became preferred, particularly as blood gas analysis and ventilator technologies simultaneously matured, spurred at least in part by the polio epidemics of the 1950s.¹⁰

NIPPV reemerged in the 1980s for use in chronic conditions. First, continuous positive airway pressure (CPAP) came into use for obstructive sleep apnea,¹¹ followed by noninvasive positive-pressure volume ventilation in neuromuscular diseases.¹² Bilevel positive pressure devices (ie, with separate inspiratory and expiratory pressures) soon followed, again initially for obstructive sleep apnea¹³ and then for diverse neuromuscular diseases.¹⁴

NIPPV is now a mainstream therapy for diverse conditions in acute and chronic care.³ One reason we now use it in acute conditions is to avoid the complications associated with intubation.

Some clinicians initially resisted using NIPPV, concerned that it demanded too much of the nurses’ time¹⁵ and was costly.¹⁶ However, in a 1997 study in patients with COPD and acute respiratory failure, Nava et al¹⁷ found that NIPPV was no more expensive and no more demanding of staff resources than invasive mechanical ventilation in the first 48 hours of ventilation. Further, after the first few days of ventilation, NIPPV put fewer time demands on physicians and nurses than did invasive mechanical ventilation.

THREE MODES: CPAP, PRESSURE-LIMITED, VOLUME-LIMITED

The term “noninvasive ventilation” generally encompasses various forms of positive pressure ventilation. However, negative pressure ventilation, in the form of diaphragm pacing, may regain a foothold in the devices used for respiratory support.¹⁸ We therefore favor the term “NIPPV” in this review.

NIPPV IN ACUTE RESPIRATORY FAILURE

The main reasons to use NIPPV instead of invasive ventilation in acute care are to avoid the complications of invasive ventilation, to improve outcomes (eg, reduce mortality rates, decrease hospital length of stay), and to decrease the cost of care.

NIPPV is the standard of care for acute exacerbations of COPD

In a meta-analysis of eight randomized controlled trials,²⁴ the specific advantages of NIPPV compared with usual care in acute exacerbations of COPD included:

• A lower risk of treatment failure, defined as death, need for intubation, or inability to tolerate the treatment (relative risk [RR] 0.51, number needed to treat [NNT] to prevent one treatment failure = 5)
• A lower risk of intubation (RR 0.43, NNT = 5)
• A lower mortality rate (RR 0.41, NNT = 8)
• A lower risk of complications (RR 0.32, NNT = 3)
• A shorter hospital length of stay (by about 3 days).

Mechanisms by which NIPPV may impart these benefits include reducing the work of breathing, unloading the respiratory muscles, lessening diaphragmatic pressure swings, reducing the respiratory rate, eliminating diaphragmatic work, and counteracting the threshold loading effects of auto-positive end-expiratory pressure (auto-PEEP).^24–26

Also, if a patient with COPD is intubated, NIPPV seems to help after the tube is removed, preventing postextubation respiratory failure and facilitating weaning from invasive ventilation.²⁷ These topics are discussed below.

A Cochrane systematic review²⁴ concluded that NIPPV should be tried early in the course of respiratory failure, before severe acidosis develops. The patients in the studies in this review all had partial pressure of arterial carbon dioxide (Paco₂) levels greater than 45 mm Hg.

In patients with severe respiratory acidosis (pH < 7.25), NIPPV failure rates are greater than 50%. However, trying NIPPV may still be justified, even in the presence of hypercapnic encephalopathy, as long as no other indications for invasive support and facilities for prompt endotracheal intubation are available. ¹

However, in another systematic review,²⁶ in patients with mild COPD exacerbations (pH > 7.35), NIPPV was no more effective than standard medical therapy in preventing acute respiratory failure, preventing death, or reducing length of hospitalization. Moreover, nearly 50% of the patients could not tolerate NIPPV.

The Three Interventions in Cardiogenic Pulmonary Oedema (3CPO) trial,²⁸ with 1,156 patients, was the largest randomized trial to compare NIPPV and standard oxygen therapy for acute pulmonary edema. It found that NIPPV (either CPAP or noninvasive intermittent positive pressure ventilation) was significantly better than standard oxygen therapy (through a variable-delivery oxygen mask with a reservoir) in the first hour of treatment in terms of the dyspnea score, heart rate, acidosis, and hypercapnia. However, there were no significant differences between groups in the 7- or 30-day mortality rates, the rates of intubation, rates of admission to the critical care unit, or in the mean length of hospital stay.

In contrast, several smaller randomized trials and meta-analyses showed lower intubation and mortality rates with NIPPV.^29,30 Factors that may account for those differences include a much lower intubation rate in the 3CPO trial (2.9% overall, compared with 20% with conventional therapy in other trials), a higher mortality rate in the 3CPO trial, and methodologic differences (eg, patients for whom standard therapy failed in the 3CPO trial received rescue NIPPV).

If NIPPV is beneficial in cardiogenic pulmonary edema, the mechanisms are probably its favorable hemodynamic effects and its positive end-expiratory pressure (PEEP) effect on flooded alveoli. Specifically, positive intrathoracic pressure can be expected to reduce both preload and afterload, with improvement in the cardiac index and reduced work of breathing. ^31,32

Notwithstanding the possible lack of impact of NIPPV on death or intubation rates in this setting, the intervention rapidly improves dyspnea and respiratory and metabolic abnormalities and should be considered for treatment of cardiogenic pulmonary edema associated with severe respiratory distress. A subgroup in which the NIPPV may reduce intubation rates is those with hypercapnia.³³ A concern that NIPPV may increase the rate of myocardial infarction³⁴ was not confirmed in the 3CPO trial.²⁸ Interestingly, there were no differences in outcomes between CPAP and noninvasive intermittent positive pressure ventilation in this setting.^28,34,35

Immunocompromised patients with acute respiratory failure

A particular challenge of NIPPV in immunocompromised patients, particularly compared with its use in COPD exacerbation or cardiogenic pulmonary edema, is that the underlying pathophysiology of respiratory dysfunction in immunocompromised patients may not be readily reversible. Therefore, its application in this group may need to follow clearly defined indications.

In one trial,²⁰ inclusion criteria were:

• Immune suppression (due to neutropenia after chemotherapy or bone marrow transplantation, immunosuppressive drugs for organ transplantation, corticosteroids, cytotoxic therapy for nonmalignant conditions, or the acquired immunodeficiency syndrome)
• Persistent pulmonary infiltrates
• Fever (temperature > 38.3°C; 100.9°F)
• A respiratory rate greater than 30 breaths per minute
• Severe dyspnea at rest
• Early hypoxemic acute respiratory failure, defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Pao₂/Fio₂ ratio) less than 200 while on oxygen.

Compared with patients who received conventional treatment, fewer of those randomized to additional intermittent noninvasive ventilation had to be intubated (46% vs 77%, P = .03), suffered serious complications (50% vs 81%, P = .02), or died in the intensive care unit (38% vs 69%, P = .03) or in the hospital (50% vs 81%, P = .02).

Similarly, in a randomized trial in 40 patients with acute respiratory failure after solid organ transplantation, more patients in the NIPPV group than in the control group had an improvement in the Pao₂/Fio₂ ratio within the first hour (70% vs 25%, P = .004) or a sustained improvement in the Pao₂/Fio₂ ratio (60% vs 25%, P = .03); fewer of them needed endotracheal intubation (20% vs 70%, P = .002); fewer of them died of complications (20% vs 50%, P = .05); they had a shorter length of stay in the intensive care unit (mean 5.5 vs 9 days, P = .03); and fewer of them died in the intensive care unit (20% vs 50%, P = .05). There was, however, no difference in the overall hospital mortality rate.³⁶

MAY NOT HELP AFTER EXTUBATION, EXCEPT IN SPECIFIC CASES

NIPPV has been used to treat respiratory failure after extubation,^22,37 to prevent acute respiratory failure after failure of weaning,^38–41 and to support breathing in patients who failed a trial of spontaneous breathing.^42–45

Unfortunately, the evidence for using NIPPV in respiratory failure after extubation, including unplanned extubation, appears to be unfavorable, except possibly in patients with chronic pulmonary disease (particularly COPD and possibly obesity) and hypercapnia. An international consensus report stated that NIPPV should be considered in patients with hypercapnic respiratory insufficiency, especially those with COPD, to shorten the duration of intubation, but that it should not be routinely used in extubation respiratory failure.⁴⁶

Treatment of respiratory failure after extubation

Two recent randomized controlled trials compared NIPPV and standard care in patients who met the criteria for readiness for extubation but who developed respiratory failure after mechanical ventilation was discontinued. ^22,37 Those two studies showed a longer time to reintubation for patients randomized to NIPPV but no differences in the rate of reintubation between the two groups and no difference in the lengths of stay in the intensive care unit.

Of greater concern, one study showed a higher rate of death in the intensive care unit in the NIPPV group than in the standard therapy group (25% vs 14%, respectively).²² This finding suggests that NIPPV delayed necessary reintubation in patients developing respiratory failure after extubation, with a consequent risk of fatal complications.

Other studies used NIPPV to prevent respiratory failure after extubation rather than wait to apply it after respiratory failure developed.^38–41

Nava et al,⁴⁰ in a trial in patients successfully weaned but considered to be at risk of reintubation, found that fewer of those randomized to NIPPV had to be reintubated than those who received standard care (8% vs 24%), and 10% fewer of them died in the intensive care unit. Risk factors for reintubation (and therefore eligibility criteria for this trial) included a Paco₂ higher than 45 mm Hg, more than one consecutive failure of weaning, chronic heart failure, other comorbidity, weak cough, or stridor.

Extubated patients are a heterogeneous group, so if some subgroups benefit from a transition to NIPPV after extubation, it will be important to identify them. For instance, a subgroup analysis of a study by Ferrer et al³⁸ indicated the survival benefit of NIPPV after extubation was limited to patients with chronic respiratory disorders and hypercapnia during a trial of spontaneous breathing.

In a subsequent successful test of this hypothesis, a randomized trial showed that the early use of noninvasive ventilation in patients with hypercapnia after a trial of spontaneous breathing and with chronic respiratory disorders (COPD, chronic bronchitis, bronchiectasis, obesity-hypoventilation, sequelae of tuberculosis, chest wall deformity, or chronic persistent asthma) reduced the risk of respiratory failure after extubation and the risk of death within the first 90 days.³⁹

Others in which this approach may be helpful are obese patients who have high Paco₂ levels. Compared with historical controls, 62 patients with a body mass index greater than 35 kg/m² who received NIPPV in the 48 hours after extubation had a lower rate of respiratory failure, shorter lengths of stay in the intensive care unit and hospital, and, in the subgroup with hypercapnia, a lower hospital mortality rate.⁴¹

NIPPV to facilitate weaning

In several studies, mechanically ventilated patients who had failed a trial of spontaneous breathing were randomized to undergo either accelerated weaning, extubation, and NIPPV or conventional weaning with pressure support via mechanical ventilation.^42–46 Most patients developed hypercapnia during the spontaneous breathing trials, and most of the patients had COPD.

A meta-analysis⁴⁷ of the randomized trials of this approach concluded that, compared with continued invasive ventilation, NIPPV decreased the risk of death (relative risk 0.41) and of ventilator-associated pneumonia (relative risk 0.28) and reduced the total duration of mechanical ventilation by a weighted mean difference of 7.33 days. The benefits appeared to be most significant in patients with COPD.

NIPPV IN ASTHMA AND STATUS ASTHMATICUS

Noninvasive ventilation is an attractive alternative to intubation for patients with status asthmaticus, given the challenges and conflicting demands of maintaining ventilation despite severe airway obstruction.

In a 1996 prospective study of 17 episodes of asthma associated with acute respiratory failure, Meduri et al⁴⁸ showed that NIPPV could progressively improve the pH and the Paco₂ over 12 to 24 hours and reduce the respiratory rate.

In a subsequent controlled trial, Soroksky et al⁴⁹ randomized 30 patients presenting to an emergency room with a severe asthma attack to NIPPV with conventional therapy vs conventional therapy only. The study group had a significantly greater increase in the forced expiratory volume in 1 second compared with the control group (54% vs 29%, respectively) and a lower hospitalization rate (18% vs 63%).

Another randomized trial of NIPPV, in patients with status asthmaticus presenting to an emergency room, was prematurely terminated due to a physician treatment bias that favored NIPPV.⁵⁰ The preliminary results of that study showed a 7.3% higher intubation rate in the control group than in the NIPPV group, along with trends toward a lower intubation rate, a shorter length of hospital stay, and lower hospital charges in the NIPPV group.

Despite these initial favorable results, a Cochrane review concluded that the use of NIPPV in patients with status asthmaticus is controversial.⁵¹ NIPPV can be tried in selected patients such as those with mild to moderate respiratory distress (respiratory rate greater than 25 breaths per minute, use of accessory muscles to breathe, difficulty speaking), an arterial pH of 7.25 to 7.35, and a Paco₂ of 45 to 55 mm Hg.⁵² Patients with impending respiratory failure or the inability to protect the airway should probably not be considered for NIPPV.⁵²

IN ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME

The most challenging application of NIPPV may be in patients with acute lung injury and the acute respiratory distress syndrome.

Initial trials of NIPPV in this setting have been disappointing, and a meta-analysis of the topic concluded that NIPPV was unlikely to have any significant benefit.⁵³ An earlier study that used CPAP in patients with acute respiratory failure predominantly due to acute lung injury showed early physiologic improvements but no reduction in the need for intubation, no improvement in outcomes, and a higher rate of adverse events, including cardiac arrest, in those randomized to CPAP.⁵⁴

A subsequent observational cohort specifically identified shock, metabolic acidosis, and severe hypoxemia as predictors of NIPPV failure.⁵⁵

A more recent prospective study demonstrated that NIPPV improved gas exchange and obviated intubation in 54% of patients, with a consequent reduction in ventilator-associated pneumonia and a lower rate of death in the intensive care unit.⁵⁶ A Simplified Acute Physiology Score (SAPS) II greater than 34 and a Pao₂/Fio₂ ratio less than 175 after 1 hour of NIPPV were identified as predicting that NIPPV would fail.⁵⁶

MISCELLANEOUS APPLICATIONS

The more widespread use of NIPPV has encouraged its use in other acute situations, including during procedures such as percutaneous endoscopic gastrostomy (PEG)^57,58 or bronchoscopy,^59,60 for palliative use in patients listed as “do-not-intubate,”^61–63 and for oxygenation before intubation.⁶⁴

NIPPV during PEG tube insertion

NIPPV during PEG tube placement is particularly useful for patients with neuromuscular diseases who are at a combined risk of aspiration, poor oral intake, and respiratory failure during procedures. The experience with patients with amyotrophic lateral sclerosis⁵⁸ and Duchenne muscular dystrophy⁵⁷ indicates that even patients at high risk of respiratory failure during procedures can be successfully managed with NIPPV. The most recent practice parameters for patients with amyotrophic lateral sclerosis propose that patients with dysphagia may be exposed to less risk if the PEG procedure is performed when the forced vital capacity is greater than 50% of predicted.⁶⁵

In randomized trials of CPAP⁵⁹ or pressure-support NIPPV⁶⁰ in high-risk hypoxemic patients who needed diagnostic bronchoscopy, patients in the intervention groups fared better than those who received oxygen alone, with better oxygenation during and after the procedure and a lower risk of postprocedure respiratory failure. Improved hemodynamics with a lower mean heart rate and a stable mean arterial pressure were also reported in one of those studies.⁶⁰

Palliative use in ‘do-not-intubate’ patients

In patients who decline intubation, NIPPV appears to be most effective in reversing acute respiratory failure and improving mortality rates in those with COPD or with cardiogenic pulmonary edema.^61,62 Controversy surrounding the use of NIPPV in “do-not-intubate” patients, particularly as a potentially uncomfortable life support technique, has been addressed by a task force of the Society of Critical Care Medicine, which recommends that it be applied only after careful discussion of goals of care and parameters of treatment with patients and their families.⁶³

Oxygenation before intubation

In a prospective randomized study of oxygenation before rapid-sequence intubation via either a nonrebreather bag-valve mask or NIPPV, the NIPPV group had a higher oxygen saturation rate before, during, and after the intubation procedure.⁶⁴
 

Acknowledgment: The authors wish to thank Jodith Janes of the Cleveland Clinic Alumni Library for her help with reference citations and with locating articles.

Noninvasive positive pressure ventilation (NIPPV)—delivered via a tight-fitting mask rather than via an endotracheal tube or tracheostomy—is one of the most important advances in the management of acute respiratory failure to emerge in the past 2 decades. It is now recommended as the first choice for ventilatory support in selected patients, such as those with exacerbations of chronic obstructive pulmonary disease (COPD) or with cardiogenic pulmonary edema.^1–3 In fact, some authors suggest that using NIPPV in more than 20% of COPD patients is a characteristic of respiratory care departments that are “avid for change”⁴—change being a good thing.

However, NIPPV has not been universally accepted, with wide variations in its utilization. In a 2006 survey, it was being used in only 33% of patients with COPD or congestive heart failure, for which it might be indicated. ⁵ Some potential reasons for the low rate are that physicians do not know about it, respiratory therapists are not sufficiently trained in it, and hospitals lack the equipment to do it.⁵

Our goal in this review is to familiarize the reader with how NIPPV has evolved and with its indications and contraindications in specific acute care conditions.

FROM A VACUUM CLEANER TO THE INTENSIVE CARE UNIT

NIPPV appears to have been first tried in 1870 by Chaussier, who used a bag and face mask to resuscitate neonates.⁶

In 1936, Poulton and Oxon⁷ described their “pulmonary plus pressure machine,” which used a vacuum cleaner blower and a mask to increase the alveolar pressure and thus counteract the increased intrapulmonary pressure in patients with heart failure, pulmonary edema, Cheyne-Stokes breathing, and asthma.

In the 1940s, intermittent positive pressure breathing devices were developed for use in high-altitude aviation. Motley, Werko, and Cournand^8,9 subsequently used these devices to treat acute respiratory failure in pneumonia, pulmonary edema, near-drowning, Guillain-Barré syndrome, and acute severe asthma.

Although NIPPV was shown to be effective for acute conditions, invasive ventilation became preferred, particularly as blood gas analysis and ventilator technologies simultaneously matured, spurred at least in part by the polio epidemics of the 1950s.¹⁰

NIPPV reemerged in the 1980s for use in chronic conditions. First, continuous positive airway pressure (CPAP) came into use for obstructive sleep apnea,¹¹ followed by noninvasive positive-pressure volume ventilation in neuromuscular diseases.¹² Bilevel positive pressure devices (ie, with separate inspiratory and expiratory pressures) soon followed, again initially for obstructive sleep apnea¹³ and then for diverse neuromuscular diseases.¹⁴

NIPPV is now a mainstream therapy for diverse conditions in acute and chronic care.³ One reason we now use it in acute conditions is to avoid the complications associated with intubation.

Some clinicians initially resisted using NIPPV, concerned that it demanded too much of the nurses’ time¹⁵ and was costly.¹⁶ However, in a 1997 study in patients with COPD and acute respiratory failure, Nava et al¹⁷ found that NIPPV was no more expensive and no more demanding of staff resources than invasive mechanical ventilation in the first 48 hours of ventilation. Further, after the first few days of ventilation, NIPPV put fewer time demands on physicians and nurses than did invasive mechanical ventilation.

THREE MODES: CPAP, PRESSURE-LIMITED, VOLUME-LIMITED

The term “noninvasive ventilation” generally encompasses various forms of positive pressure ventilation. However, negative pressure ventilation, in the form of diaphragm pacing, may regain a foothold in the devices used for respiratory support.¹⁸ We therefore favor the term “NIPPV” in this review.

NIPPV IN ACUTE RESPIRATORY FAILURE

The main reasons to use NIPPV instead of invasive ventilation in acute care are to avoid the complications of invasive ventilation, to improve outcomes (eg, reduce mortality rates, decrease hospital length of stay), and to decrease the cost of care.

NIPPV is the standard of care for acute exacerbations of COPD

In a meta-analysis of eight randomized controlled trials,²⁴ the specific advantages of NIPPV compared with usual care in acute exacerbations of COPD included:

• A lower risk of treatment failure, defined as death, need for intubation, or inability to tolerate the treatment (relative risk [RR] 0.51, number needed to treat [NNT] to prevent one treatment failure = 5)
• A lower risk of intubation (RR 0.43, NNT = 5)
• A lower mortality rate (RR 0.41, NNT = 8)
• A lower risk of complications (RR 0.32, NNT = 3)
• A shorter hospital length of stay (by about 3 days).

Mechanisms by which NIPPV may impart these benefits include reducing the work of breathing, unloading the respiratory muscles, lessening diaphragmatic pressure swings, reducing the respiratory rate, eliminating diaphragmatic work, and counteracting the threshold loading effects of auto-positive end-expiratory pressure (auto-PEEP).^24–26

Also, if a patient with COPD is intubated, NIPPV seems to help after the tube is removed, preventing postextubation respiratory failure and facilitating weaning from invasive ventilation.²⁷ These topics are discussed below.

A Cochrane systematic review²⁴ concluded that NIPPV should be tried early in the course of respiratory failure, before severe acidosis develops. The patients in the studies in this review all had partial pressure of arterial carbon dioxide (Paco₂) levels greater than 45 mm Hg.

In patients with severe respiratory acidosis (pH < 7.25), NIPPV failure rates are greater than 50%. However, trying NIPPV may still be justified, even in the presence of hypercapnic encephalopathy, as long as no other indications for invasive support and facilities for prompt endotracheal intubation are available. ¹

However, in another systematic review,²⁶ in patients with mild COPD exacerbations (pH > 7.35), NIPPV was no more effective than standard medical therapy in preventing acute respiratory failure, preventing death, or reducing length of hospitalization. Moreover, nearly 50% of the patients could not tolerate NIPPV.

The Three Interventions in Cardiogenic Pulmonary Oedema (3CPO) trial,²⁸ with 1,156 patients, was the largest randomized trial to compare NIPPV and standard oxygen therapy for acute pulmonary edema. It found that NIPPV (either CPAP or noninvasive intermittent positive pressure ventilation) was significantly better than standard oxygen therapy (through a variable-delivery oxygen mask with a reservoir) in the first hour of treatment in terms of the dyspnea score, heart rate, acidosis, and hypercapnia. However, there were no significant differences between groups in the 7- or 30-day mortality rates, the rates of intubation, rates of admission to the critical care unit, or in the mean length of hospital stay.

In contrast, several smaller randomized trials and meta-analyses showed lower intubation and mortality rates with NIPPV.^29,30 Factors that may account for those differences include a much lower intubation rate in the 3CPO trial (2.9% overall, compared with 20% with conventional therapy in other trials), a higher mortality rate in the 3CPO trial, and methodologic differences (eg, patients for whom standard therapy failed in the 3CPO trial received rescue NIPPV).

If NIPPV is beneficial in cardiogenic pulmonary edema, the mechanisms are probably its favorable hemodynamic effects and its positive end-expiratory pressure (PEEP) effect on flooded alveoli. Specifically, positive intrathoracic pressure can be expected to reduce both preload and afterload, with improvement in the cardiac index and reduced work of breathing. ^31,32

Notwithstanding the possible lack of impact of NIPPV on death or intubation rates in this setting, the intervention rapidly improves dyspnea and respiratory and metabolic abnormalities and should be considered for treatment of cardiogenic pulmonary edema associated with severe respiratory distress. A subgroup in which the NIPPV may reduce intubation rates is those with hypercapnia.³³ A concern that NIPPV may increase the rate of myocardial infarction³⁴ was not confirmed in the 3CPO trial.²⁸ Interestingly, there were no differences in outcomes between CPAP and noninvasive intermittent positive pressure ventilation in this setting.^28,34,35

Immunocompromised patients with acute respiratory failure

A particular challenge of NIPPV in immunocompromised patients, particularly compared with its use in COPD exacerbation or cardiogenic pulmonary edema, is that the underlying pathophysiology of respiratory dysfunction in immunocompromised patients may not be readily reversible. Therefore, its application in this group may need to follow clearly defined indications.

In one trial,²⁰ inclusion criteria were:

• Immune suppression (due to neutropenia after chemotherapy or bone marrow transplantation, immunosuppressive drugs for organ transplantation, corticosteroids, cytotoxic therapy for nonmalignant conditions, or the acquired immunodeficiency syndrome)
• Persistent pulmonary infiltrates
• Fever (temperature > 38.3°C; 100.9°F)
• A respiratory rate greater than 30 breaths per minute
• Severe dyspnea at rest
• Early hypoxemic acute respiratory failure, defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Pao₂/Fio₂ ratio) less than 200 while on oxygen.

Compared with patients who received conventional treatment, fewer of those randomized to additional intermittent noninvasive ventilation had to be intubated (46% vs 77%, P = .03), suffered serious complications (50% vs 81%, P = .02), or died in the intensive care unit (38% vs 69%, P = .03) or in the hospital (50% vs 81%, P = .02).

Similarly, in a randomized trial in 40 patients with acute respiratory failure after solid organ transplantation, more patients in the NIPPV group than in the control group had an improvement in the Pao₂/Fio₂ ratio within the first hour (70% vs 25%, P = .004) or a sustained improvement in the Pao₂/Fio₂ ratio (60% vs 25%, P = .03); fewer of them needed endotracheal intubation (20% vs 70%, P = .002); fewer of them died of complications (20% vs 50%, P = .05); they had a shorter length of stay in the intensive care unit (mean 5.5 vs 9 days, P = .03); and fewer of them died in the intensive care unit (20% vs 50%, P = .05). There was, however, no difference in the overall hospital mortality rate.³⁶

MAY NOT HELP AFTER EXTUBATION, EXCEPT IN SPECIFIC CASES

NIPPV has been used to treat respiratory failure after extubation,^22,37 to prevent acute respiratory failure after failure of weaning,^38–41 and to support breathing in patients who failed a trial of spontaneous breathing.^42–45

Unfortunately, the evidence for using NIPPV in respiratory failure after extubation, including unplanned extubation, appears to be unfavorable, except possibly in patients with chronic pulmonary disease (particularly COPD and possibly obesity) and hypercapnia. An international consensus report stated that NIPPV should be considered in patients with hypercapnic respiratory insufficiency, especially those with COPD, to shorten the duration of intubation, but that it should not be routinely used in extubation respiratory failure.⁴⁶

Treatment of respiratory failure after extubation

Two recent randomized controlled trials compared NIPPV and standard care in patients who met the criteria for readiness for extubation but who developed respiratory failure after mechanical ventilation was discontinued. ^22,37 Those two studies showed a longer time to reintubation for patients randomized to NIPPV but no differences in the rate of reintubation between the two groups and no difference in the lengths of stay in the intensive care unit.

Of greater concern, one study showed a higher rate of death in the intensive care unit in the NIPPV group than in the standard therapy group (25% vs 14%, respectively).²² This finding suggests that NIPPV delayed necessary reintubation in patients developing respiratory failure after extubation, with a consequent risk of fatal complications.

Other studies used NIPPV to prevent respiratory failure after extubation rather than wait to apply it after respiratory failure developed.^38–41

Nava et al,⁴⁰ in a trial in patients successfully weaned but considered to be at risk of reintubation, found that fewer of those randomized to NIPPV had to be reintubated than those who received standard care (8% vs 24%), and 10% fewer of them died in the intensive care unit. Risk factors for reintubation (and therefore eligibility criteria for this trial) included a Paco₂ higher than 45 mm Hg, more than one consecutive failure of weaning, chronic heart failure, other comorbidity, weak cough, or stridor.

Extubated patients are a heterogeneous group, so if some subgroups benefit from a transition to NIPPV after extubation, it will be important to identify them. For instance, a subgroup analysis of a study by Ferrer et al³⁸ indicated the survival benefit of NIPPV after extubation was limited to patients with chronic respiratory disorders and hypercapnia during a trial of spontaneous breathing.

In a subsequent successful test of this hypothesis, a randomized trial showed that the early use of noninvasive ventilation in patients with hypercapnia after a trial of spontaneous breathing and with chronic respiratory disorders (COPD, chronic bronchitis, bronchiectasis, obesity-hypoventilation, sequelae of tuberculosis, chest wall deformity, or chronic persistent asthma) reduced the risk of respiratory failure after extubation and the risk of death within the first 90 days.³⁹

Others in which this approach may be helpful are obese patients who have high Paco₂ levels. Compared with historical controls, 62 patients with a body mass index greater than 35 kg/m² who received NIPPV in the 48 hours after extubation had a lower rate of respiratory failure, shorter lengths of stay in the intensive care unit and hospital, and, in the subgroup with hypercapnia, a lower hospital mortality rate.⁴¹

NIPPV to facilitate weaning

In several studies, mechanically ventilated patients who had failed a trial of spontaneous breathing were randomized to undergo either accelerated weaning, extubation, and NIPPV or conventional weaning with pressure support via mechanical ventilation.^42–46 Most patients developed hypercapnia during the spontaneous breathing trials, and most of the patients had COPD.

A meta-analysis⁴⁷ of the randomized trials of this approach concluded that, compared with continued invasive ventilation, NIPPV decreased the risk of death (relative risk 0.41) and of ventilator-associated pneumonia (relative risk 0.28) and reduced the total duration of mechanical ventilation by a weighted mean difference of 7.33 days. The benefits appeared to be most significant in patients with COPD.

NIPPV IN ASTHMA AND STATUS ASTHMATICUS

Noninvasive ventilation is an attractive alternative to intubation for patients with status asthmaticus, given the challenges and conflicting demands of maintaining ventilation despite severe airway obstruction.

In a 1996 prospective study of 17 episodes of asthma associated with acute respiratory failure, Meduri et al⁴⁸ showed that NIPPV could progressively improve the pH and the Paco₂ over 12 to 24 hours and reduce the respiratory rate.

In a subsequent controlled trial, Soroksky et al⁴⁹ randomized 30 patients presenting to an emergency room with a severe asthma attack to NIPPV with conventional therapy vs conventional therapy only. The study group had a significantly greater increase in the forced expiratory volume in 1 second compared with the control group (54% vs 29%, respectively) and a lower hospitalization rate (18% vs 63%).

Another randomized trial of NIPPV, in patients with status asthmaticus presenting to an emergency room, was prematurely terminated due to a physician treatment bias that favored NIPPV.⁵⁰ The preliminary results of that study showed a 7.3% higher intubation rate in the control group than in the NIPPV group, along with trends toward a lower intubation rate, a shorter length of hospital stay, and lower hospital charges in the NIPPV group.

Despite these initial favorable results, a Cochrane review concluded that the use of NIPPV in patients with status asthmaticus is controversial.⁵¹ NIPPV can be tried in selected patients such as those with mild to moderate respiratory distress (respiratory rate greater than 25 breaths per minute, use of accessory muscles to breathe, difficulty speaking), an arterial pH of 7.25 to 7.35, and a Paco₂ of 45 to 55 mm Hg.⁵² Patients with impending respiratory failure or the inability to protect the airway should probably not be considered for NIPPV.⁵²

IN ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME

The most challenging application of NIPPV may be in patients with acute lung injury and the acute respiratory distress syndrome.

Initial trials of NIPPV in this setting have been disappointing, and a meta-analysis of the topic concluded that NIPPV was unlikely to have any significant benefit.⁵³ An earlier study that used CPAP in patients with acute respiratory failure predominantly due to acute lung injury showed early physiologic improvements but no reduction in the need for intubation, no improvement in outcomes, and a higher rate of adverse events, including cardiac arrest, in those randomized to CPAP.⁵⁴

A subsequent observational cohort specifically identified shock, metabolic acidosis, and severe hypoxemia as predictors of NIPPV failure.⁵⁵

A more recent prospective study demonstrated that NIPPV improved gas exchange and obviated intubation in 54% of patients, with a consequent reduction in ventilator-associated pneumonia and a lower rate of death in the intensive care unit.⁵⁶ A Simplified Acute Physiology Score (SAPS) II greater than 34 and a Pao₂/Fio₂ ratio less than 175 after 1 hour of NIPPV were identified as predicting that NIPPV would fail.⁵⁶

MISCELLANEOUS APPLICATIONS

The more widespread use of NIPPV has encouraged its use in other acute situations, including during procedures such as percutaneous endoscopic gastrostomy (PEG)^57,58 or bronchoscopy,^59,60 for palliative use in patients listed as “do-not-intubate,”^61–63 and for oxygenation before intubation.⁶⁴

NIPPV during PEG tube insertion

NIPPV during PEG tube placement is particularly useful for patients with neuromuscular diseases who are at a combined risk of aspiration, poor oral intake, and respiratory failure during procedures. The experience with patients with amyotrophic lateral sclerosis⁵⁸ and Duchenne muscular dystrophy⁵⁷ indicates that even patients at high risk of respiratory failure during procedures can be successfully managed with NIPPV. The most recent practice parameters for patients with amyotrophic lateral sclerosis propose that patients with dysphagia may be exposed to less risk if the PEG procedure is performed when the forced vital capacity is greater than 50% of predicted.⁶⁵

In randomized trials of CPAP⁵⁹ or pressure-support NIPPV⁶⁰ in high-risk hypoxemic patients who needed diagnostic bronchoscopy, patients in the intervention groups fared better than those who received oxygen alone, with better oxygenation during and after the procedure and a lower risk of postprocedure respiratory failure. Improved hemodynamics with a lower mean heart rate and a stable mean arterial pressure were also reported in one of those studies.⁶⁰

Palliative use in ‘do-not-intubate’ patients

In patients who decline intubation, NIPPV appears to be most effective in reversing acute respiratory failure and improving mortality rates in those with COPD or with cardiogenic pulmonary edema.^61,62 Controversy surrounding the use of NIPPV in “do-not-intubate” patients, particularly as a potentially uncomfortable life support technique, has been addressed by a task force of the Society of Critical Care Medicine, which recommends that it be applied only after careful discussion of goals of care and parameters of treatment with patients and their families.⁶³

Oxygenation before intubation

In a prospective randomized study of oxygenation before rapid-sequence intubation via either a nonrebreather bag-valve mask or NIPPV, the NIPPV group had a higher oxygen saturation rate before, during, and after the intubation procedure.⁶⁴
 

Acknowledgment: The authors wish to thank Jodith Janes of the Cleveland Clinic Alumni Library for her help with reference citations and with locating articles.

Noninvasive positive pressure ventilation (NIPPV)—delivered via a tight-fitting mask rather than via an endotracheal tube or tracheostomy—is one of the most important advances in the management of acute respiratory failure to emerge in the past 2 decades. It is now recommended as the first choice for ventilatory support in selected patients, such as those with exacerbations of chronic obstructive pulmonary disease (COPD) or with cardiogenic pulmonary edema.^1–3 In fact, some authors suggest that using NIPPV in more than 20% of COPD patients is a characteristic of respiratory care departments that are “avid for change”⁴—change being a good thing.

However, NIPPV has not been universally accepted, with wide variations in its utilization. In a 2006 survey, it was being used in only 33% of patients with COPD or congestive heart failure, for which it might be indicated. ⁵ Some potential reasons for the low rate are that physicians do not know about it, respiratory therapists are not sufficiently trained in it, and hospitals lack the equipment to do it.⁵

Our goal in this review is to familiarize the reader with how NIPPV has evolved and with its indications and contraindications in specific acute care conditions.

FROM A VACUUM CLEANER TO THE INTENSIVE CARE UNIT

NIPPV appears to have been first tried in 1870 by Chaussier, who used a bag and face mask to resuscitate neonates.⁶

In 1936, Poulton and Oxon⁷ described their “pulmonary plus pressure machine,” which used a vacuum cleaner blower and a mask to increase the alveolar pressure and thus counteract the increased intrapulmonary pressure in patients with heart failure, pulmonary edema, Cheyne-Stokes breathing, and asthma.

In the 1940s, intermittent positive pressure breathing devices were developed for use in high-altitude aviation. Motley, Werko, and Cournand^8,9 subsequently used these devices to treat acute respiratory failure in pneumonia, pulmonary edema, near-drowning, Guillain-Barré syndrome, and acute severe asthma.

Although NIPPV was shown to be effective for acute conditions, invasive ventilation became preferred, particularly as blood gas analysis and ventilator technologies simultaneously matured, spurred at least in part by the polio epidemics of the 1950s.¹⁰

NIPPV reemerged in the 1980s for use in chronic conditions. First, continuous positive airway pressure (CPAP) came into use for obstructive sleep apnea,¹¹ followed by noninvasive positive-pressure volume ventilation in neuromuscular diseases.¹² Bilevel positive pressure devices (ie, with separate inspiratory and expiratory pressures) soon followed, again initially for obstructive sleep apnea¹³ and then for diverse neuromuscular diseases.¹⁴

NIPPV is now a mainstream therapy for diverse conditions in acute and chronic care.³ One reason we now use it in acute conditions is to avoid the complications associated with intubation.

Some clinicians initially resisted using NIPPV, concerned that it demanded too much of the nurses’ time¹⁵ and was costly.¹⁶ However, in a 1997 study in patients with COPD and acute respiratory failure, Nava et al¹⁷ found that NIPPV was no more expensive and no more demanding of staff resources than invasive mechanical ventilation in the first 48 hours of ventilation. Further, after the first few days of ventilation, NIPPV put fewer time demands on physicians and nurses than did invasive mechanical ventilation.

THREE MODES: CPAP, PRESSURE-LIMITED, VOLUME-LIMITED

The term “noninvasive ventilation” generally encompasses various forms of positive pressure ventilation. However, negative pressure ventilation, in the form of diaphragm pacing, may regain a foothold in the devices used for respiratory support.¹⁸ We therefore favor the term “NIPPV” in this review.

NIPPV IN ACUTE RESPIRATORY FAILURE

The main reasons to use NIPPV instead of invasive ventilation in acute care are to avoid the complications of invasive ventilation, to improve outcomes (eg, reduce mortality rates, decrease hospital length of stay), and to decrease the cost of care.

NIPPV is the standard of care for acute exacerbations of COPD

In a meta-analysis of eight randomized controlled trials,²⁴ the specific advantages of NIPPV compared with usual care in acute exacerbations of COPD included:

• A lower risk of treatment failure, defined as death, need for intubation, or inability to tolerate the treatment (relative risk [RR] 0.51, number needed to treat [NNT] to prevent one treatment failure = 5)
• A lower risk of intubation (RR 0.43, NNT = 5)
• A lower mortality rate (RR 0.41, NNT = 8)
• A lower risk of complications (RR 0.32, NNT = 3)
• A shorter hospital length of stay (by about 3 days).

Mechanisms by which NIPPV may impart these benefits include reducing the work of breathing, unloading the respiratory muscles, lessening diaphragmatic pressure swings, reducing the respiratory rate, eliminating diaphragmatic work, and counteracting the threshold loading effects of auto-positive end-expiratory pressure (auto-PEEP).^24–26

Also, if a patient with COPD is intubated, NIPPV seems to help after the tube is removed, preventing postextubation respiratory failure and facilitating weaning from invasive ventilation.²⁷ These topics are discussed below.

A Cochrane systematic review²⁴ concluded that NIPPV should be tried early in the course of respiratory failure, before severe acidosis develops. The patients in the studies in this review all had partial pressure of arterial carbon dioxide (Paco₂) levels greater than 45 mm Hg.

In patients with severe respiratory acidosis (pH < 7.25), NIPPV failure rates are greater than 50%. However, trying NIPPV may still be justified, even in the presence of hypercapnic encephalopathy, as long as no other indications for invasive support and facilities for prompt endotracheal intubation are available. ¹

However, in another systematic review,²⁶ in patients with mild COPD exacerbations (pH > 7.35), NIPPV was no more effective than standard medical therapy in preventing acute respiratory failure, preventing death, or reducing length of hospitalization. Moreover, nearly 50% of the patients could not tolerate NIPPV.

The Three Interventions in Cardiogenic Pulmonary Oedema (3CPO) trial,²⁸ with 1,156 patients, was the largest randomized trial to compare NIPPV and standard oxygen therapy for acute pulmonary edema. It found that NIPPV (either CPAP or noninvasive intermittent positive pressure ventilation) was significantly better than standard oxygen therapy (through a variable-delivery oxygen mask with a reservoir) in the first hour of treatment in terms of the dyspnea score, heart rate, acidosis, and hypercapnia. However, there were no significant differences between groups in the 7- or 30-day mortality rates, the rates of intubation, rates of admission to the critical care unit, or in the mean length of hospital stay.

In contrast, several smaller randomized trials and meta-analyses showed lower intubation and mortality rates with NIPPV.^29,30 Factors that may account for those differences include a much lower intubation rate in the 3CPO trial (2.9% overall, compared with 20% with conventional therapy in other trials), a higher mortality rate in the 3CPO trial, and methodologic differences (eg, patients for whom standard therapy failed in the 3CPO trial received rescue NIPPV).

If NIPPV is beneficial in cardiogenic pulmonary edema, the mechanisms are probably its favorable hemodynamic effects and its positive end-expiratory pressure (PEEP) effect on flooded alveoli. Specifically, positive intrathoracic pressure can be expected to reduce both preload and afterload, with improvement in the cardiac index and reduced work of breathing. ^31,32

Notwithstanding the possible lack of impact of NIPPV on death or intubation rates in this setting, the intervention rapidly improves dyspnea and respiratory and metabolic abnormalities and should be considered for treatment of cardiogenic pulmonary edema associated with severe respiratory distress. A subgroup in which the NIPPV may reduce intubation rates is those with hypercapnia.³³ A concern that NIPPV may increase the rate of myocardial infarction³⁴ was not confirmed in the 3CPO trial.²⁸ Interestingly, there were no differences in outcomes between CPAP and noninvasive intermittent positive pressure ventilation in this setting.^28,34,35

Immunocompromised patients with acute respiratory failure

A particular challenge of NIPPV in immunocompromised patients, particularly compared with its use in COPD exacerbation or cardiogenic pulmonary edema, is that the underlying pathophysiology of respiratory dysfunction in immunocompromised patients may not be readily reversible. Therefore, its application in this group may need to follow clearly defined indications.

In one trial,²⁰ inclusion criteria were:

• Immune suppression (due to neutropenia after chemotherapy or bone marrow transplantation, immunosuppressive drugs for organ transplantation, corticosteroids, cytotoxic therapy for nonmalignant conditions, or the acquired immunodeficiency syndrome)
• Persistent pulmonary infiltrates
• Fever (temperature > 38.3°C; 100.9°F)
• A respiratory rate greater than 30 breaths per minute
• Severe dyspnea at rest
• Early hypoxemic acute respiratory failure, defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (Pao₂/Fio₂ ratio) less than 200 while on oxygen.

Compared with patients who received conventional treatment, fewer of those randomized to additional intermittent noninvasive ventilation had to be intubated (46% vs 77%, P = .03), suffered serious complications (50% vs 81%, P = .02), or died in the intensive care unit (38% vs 69%, P = .03) or in the hospital (50% vs 81%, P = .02).

Similarly, in a randomized trial in 40 patients with acute respiratory failure after solid organ transplantation, more patients in the NIPPV group than in the control group had an improvement in the Pao₂/Fio₂ ratio within the first hour (70% vs 25%, P = .004) or a sustained improvement in the Pao₂/Fio₂ ratio (60% vs 25%, P = .03); fewer of them needed endotracheal intubation (20% vs 70%, P = .002); fewer of them died of complications (20% vs 50%, P = .05); they had a shorter length of stay in the intensive care unit (mean 5.5 vs 9 days, P = .03); and fewer of them died in the intensive care unit (20% vs 50%, P = .05). There was, however, no difference in the overall hospital mortality rate.³⁶

MAY NOT HELP AFTER EXTUBATION, EXCEPT IN SPECIFIC CASES

NIPPV has been used to treat respiratory failure after extubation,^22,37 to prevent acute respiratory failure after failure of weaning,^38–41 and to support breathing in patients who failed a trial of spontaneous breathing.^42–45

Unfortunately, the evidence for using NIPPV in respiratory failure after extubation, including unplanned extubation, appears to be unfavorable, except possibly in patients with chronic pulmonary disease (particularly COPD and possibly obesity) and hypercapnia. An international consensus report stated that NIPPV should be considered in patients with hypercapnic respiratory insufficiency, especially those with COPD, to shorten the duration of intubation, but that it should not be routinely used in extubation respiratory failure.⁴⁶

Treatment of respiratory failure after extubation

Two recent randomized controlled trials compared NIPPV and standard care in patients who met the criteria for readiness for extubation but who developed respiratory failure after mechanical ventilation was discontinued. ^22,37 Those two studies showed a longer time to reintubation for patients randomized to NIPPV but no differences in the rate of reintubation between the two groups and no difference in the lengths of stay in the intensive care unit.

Of greater concern, one study showed a higher rate of death in the intensive care unit in the NIPPV group than in the standard therapy group (25% vs 14%, respectively).²² This finding suggests that NIPPV delayed necessary reintubation in patients developing respiratory failure after extubation, with a consequent risk of fatal complications.

Other studies used NIPPV to prevent respiratory failure after extubation rather than wait to apply it after respiratory failure developed.^38–41

Nava et al,⁴⁰ in a trial in patients successfully weaned but considered to be at risk of reintubation, found that fewer of those randomized to NIPPV had to be reintubated than those who received standard care (8% vs 24%), and 10% fewer of them died in the intensive care unit. Risk factors for reintubation (and therefore eligibility criteria for this trial) included a Paco₂ higher than 45 mm Hg, more than one consecutive failure of weaning, chronic heart failure, other comorbidity, weak cough, or stridor.

Extubated patients are a heterogeneous group, so if some subgroups benefit from a transition to NIPPV after extubation, it will be important to identify them. For instance, a subgroup analysis of a study by Ferrer et al³⁸ indicated the survival benefit of NIPPV after extubation was limited to patients with chronic respiratory disorders and hypercapnia during a trial of spontaneous breathing.

In a subsequent successful test of this hypothesis, a randomized trial showed that the early use of noninvasive ventilation in patients with hypercapnia after a trial of spontaneous breathing and with chronic respiratory disorders (COPD, chronic bronchitis, bronchiectasis, obesity-hypoventilation, sequelae of tuberculosis, chest wall deformity, or chronic persistent asthma) reduced the risk of respiratory failure after extubation and the risk of death within the first 90 days.³⁹

Others in which this approach may be helpful are obese patients who have high Paco₂ levels. Compared with historical controls, 62 patients with a body mass index greater than 35 kg/m² who received NIPPV in the 48 hours after extubation had a lower rate of respiratory failure, shorter lengths of stay in the intensive care unit and hospital, and, in the subgroup with hypercapnia, a lower hospital mortality rate.⁴¹

NIPPV to facilitate weaning

In several studies, mechanically ventilated patients who had failed a trial of spontaneous breathing were randomized to undergo either accelerated weaning, extubation, and NIPPV or conventional weaning with pressure support via mechanical ventilation.^42–46 Most patients developed hypercapnia during the spontaneous breathing trials, and most of the patients had COPD.

A meta-analysis⁴⁷ of the randomized trials of this approach concluded that, compared with continued invasive ventilation, NIPPV decreased the risk of death (relative risk 0.41) and of ventilator-associated pneumonia (relative risk 0.28) and reduced the total duration of mechanical ventilation by a weighted mean difference of 7.33 days. The benefits appeared to be most significant in patients with COPD.

NIPPV IN ASTHMA AND STATUS ASTHMATICUS

Noninvasive ventilation is an attractive alternative to intubation for patients with status asthmaticus, given the challenges and conflicting demands of maintaining ventilation despite severe airway obstruction.

In a 1996 prospective study of 17 episodes of asthma associated with acute respiratory failure, Meduri et al⁴⁸ showed that NIPPV could progressively improve the pH and the Paco₂ over 12 to 24 hours and reduce the respiratory rate.

In a subsequent controlled trial, Soroksky et al⁴⁹ randomized 30 patients presenting to an emergency room with a severe asthma attack to NIPPV with conventional therapy vs conventional therapy only. The study group had a significantly greater increase in the forced expiratory volume in 1 second compared with the control group (54% vs 29%, respectively) and a lower hospitalization rate (18% vs 63%).

Another randomized trial of NIPPV, in patients with status asthmaticus presenting to an emergency room, was prematurely terminated due to a physician treatment bias that favored NIPPV.⁵⁰ The preliminary results of that study showed a 7.3% higher intubation rate in the control group than in the NIPPV group, along with trends toward a lower intubation rate, a shorter length of hospital stay, and lower hospital charges in the NIPPV group.

Despite these initial favorable results, a Cochrane review concluded that the use of NIPPV in patients with status asthmaticus is controversial.⁵¹ NIPPV can be tried in selected patients such as those with mild to moderate respiratory distress (respiratory rate greater than 25 breaths per minute, use of accessory muscles to breathe, difficulty speaking), an arterial pH of 7.25 to 7.35, and a Paco₂ of 45 to 55 mm Hg.⁵² Patients with impending respiratory failure or the inability to protect the airway should probably not be considered for NIPPV.⁵²

IN ACUTE LUNG INJURY AND ACUTE RESPIRATORY DISTRESS SYNDROME

The most challenging application of NIPPV may be in patients with acute lung injury and the acute respiratory distress syndrome.

Initial trials of NIPPV in this setting have been disappointing, and a meta-analysis of the topic concluded that NIPPV was unlikely to have any significant benefit.⁵³ An earlier study that used CPAP in patients with acute respiratory failure predominantly due to acute lung injury showed early physiologic improvements but no reduction in the need for intubation, no improvement in outcomes, and a higher rate of adverse events, including cardiac arrest, in those randomized to CPAP.⁵⁴

A subsequent observational cohort specifically identified shock, metabolic acidosis, and severe hypoxemia as predictors of NIPPV failure.⁵⁵

A more recent prospective study demonstrated that NIPPV improved gas exchange and obviated intubation in 54% of patients, with a consequent reduction in ventilator-associated pneumonia and a lower rate of death in the intensive care unit.⁵⁶ A Simplified Acute Physiology Score (SAPS) II greater than 34 and a Pao₂/Fio₂ ratio less than 175 after 1 hour of NIPPV were identified as predicting that NIPPV would fail.⁵⁶

MISCELLANEOUS APPLICATIONS

The more widespread use of NIPPV has encouraged its use in other acute situations, including during procedures such as percutaneous endoscopic gastrostomy (PEG)^57,58 or bronchoscopy,^59,60 for palliative use in patients listed as “do-not-intubate,”^61–63 and for oxygenation before intubation.⁶⁴

NIPPV during PEG tube insertion

NIPPV during PEG tube placement is particularly useful for patients with neuromuscular diseases who are at a combined risk of aspiration, poor oral intake, and respiratory failure during procedures. The experience with patients with amyotrophic lateral sclerosis⁵⁸ and Duchenne muscular dystrophy⁵⁷ indicates that even patients at high risk of respiratory failure during procedures can be successfully managed with NIPPV. The most recent practice parameters for patients with amyotrophic lateral sclerosis propose that patients with dysphagia may be exposed to less risk if the PEG procedure is performed when the forced vital capacity is greater than 50% of predicted.⁶⁵

In randomized trials of CPAP⁵⁹ or pressure-support NIPPV⁶⁰ in high-risk hypoxemic patients who needed diagnostic bronchoscopy, patients in the intervention groups fared better than those who received oxygen alone, with better oxygenation during and after the procedure and a lower risk of postprocedure respiratory failure. Improved hemodynamics with a lower mean heart rate and a stable mean arterial pressure were also reported in one of those studies.⁶⁰

Palliative use in ‘do-not-intubate’ patients

In patients who decline intubation, NIPPV appears to be most effective in reversing acute respiratory failure and improving mortality rates in those with COPD or with cardiogenic pulmonary edema.^61,62 Controversy surrounding the use of NIPPV in “do-not-intubate” patients, particularly as a potentially uncomfortable life support technique, has been addressed by a task force of the Society of Critical Care Medicine, which recommends that it be applied only after careful discussion of goals of care and parameters of treatment with patients and their families.⁶³

Oxygenation before intubation

In a prospective randomized study of oxygenation before rapid-sequence intubation via either a nonrebreather bag-valve mask or NIPPV, the NIPPV group had a higher oxygen saturation rate before, during, and after the intubation procedure.⁶⁴
 

Acknowledgment: The authors wish to thank Jodith Janes of the Cleveland Clinic Alumni Library for her help with reference citations and with locating articles.

Orthostatic hypotension is a chronic, debilitating illness associated with common neurologic conditions (eg, diabetic neuropathy, Parkinson disease). It is common in the elderly, especially in those who are institutionalized and are using multiple medications.

Treatment can be challenging, especially if the problem is neurogenic. This condition has no cure, symptoms vary in different circumstances, treatment is nonspecific, and aggressive treatment can lead to marked supine hypertension.

This review focuses on the prevention and treatment of neurogenic causes of orthostatic hypotension. We emphasize a simple but effective patient-oriented approach to management, using a combination of nonpharmacologic strategies and drugs clinically proven to be efficacious. The recommendations and their rationale are organized in a practical and easy-to-remember format for both physicians and patients.

WHAT HAPPENS WHEN WE STAND UP?

When we stand up, the blood goes down from the chest to the distensible venous capacitance system below the diaphragm. This fluid shift produces a decrease in venous return, ventricular filling, cardiac output, and blood pressure.¹

This gravity-induced drop in blood pressure, detected by arterial baroreceptors in the aortic arch and carotid sinus, triggers a compensatory reflex tachycardia and vasoconstriction that restores normotension in the upright position. This compensatory mechanism is termed a baroreflex; it is mediated by afferent and efferent autonomic peripheral nerves and is integrated in autonomic centers in the brainstem.²

Orthostatic hypotension is the result of baroreflex failure (autonomic failure), end-organ dysfunction, or volume depletion. Injury to any limb of the baroreflex causes neurogenic orthostatic hypotension, although with afferent lesions alone, the hypotension tends to be modest and accompanied by wide fluctuations in blood pressure, including severe hypertension. Drugs can produce orthostatic hypotension by interfering with the autonomic pathways or their target end-organs or by affecting intravascular volume. Brain hypoperfusion, resulting from orthostatic hypotension from any cause, can lead to symptoms of orthostatic intolerance (eg, lightheadedness) and falls, and if the hypotension is severe, to syncope.

A DECREASE OF 20 MM HG SYSTOLIC OR 10 MM HG DIASTOLIC

The consensus definition of orthostatic hypotension is a reduction of systolic blood pressure of at least 20 mm Hg or a reduction of diastolic blood pressure of at least 10 mm Hg within 3 minutes of erect standing.³ A transient drop that occurs with abrupt standing and resolves rapidly suggests a benign condition, such as dehydration, rather than autonomic failure.

In the laboratory, patients are placed on a tilt table in the head-up position at an angle of at least 60 degrees to detect orthostatic changes in blood pressure. In the office, 1 minute of standing probably detects nearly all cases of orthostatic hypotension; however, standing beyond 2 minutes helps establish the severity (a further drop in blood pressure).⁴ Orthostatic hypotension developing after 3 minutes of standing is uncommon and may represent a reflex presyncope (eg, vasovagal) or a mild or early form of sympathetic adrenergic dysfunction.^{4, 5}

NEUROGENIC AND NONNEUROGENIC CAUSES

Orthostatic hypotension may result from neurogenic and nonneurogenic causes.

Neurogenic orthostatic hypotension can be due to neuropathy (eg, diabetic or autoimmune neuropathies) or to central lesions (eg, Parkinson disease or multiple system atrophy). Its presence, severity, and temporal course can be important clues in diagnosing Parkinson disease and differentiating it from other parkinsonian syndromes with a more ominous prognosis, such as multiple system atrophy and Lewy body dementia.

Nonneurogenic causes include cardiac impairment (eg, from myocardial infarction or aortic stenosis), reduced intravascular volume (eg, from dehydration, adrenal insufficiency), and vasodilation (eg, from fever, systemic mastocytosis).

Common drugs that cause orthostatic hypotension are diuretics, alpha-adrenoceptor blockers for prostatic hypertrophy, antihypertensive drugs, and calcium channel blockers. Insulin, levodopa, and tricyclic antidepressants can also cause vasodilation and orthostatic hypotension in predisposed patients. Poon and Braun,⁶ in a retrospective study in elderly veterans, identified hydrochlorothiazide, lisinopril (Prinivil, Zestril), trazodone (Desyrel), furosemide (Lasix), and terazosin (Hytrin) as the most common culprits.

ORTHOSTATIC HYPOTENSION IS COMMON IN THE ELDERLY

The prevalence of orthostatic hypotension is high in the elderly and depends on the characteristics of the population studied, such as age, use of medications, and comorbidities known to be associated with this problem. Orthostatic hypotension is more common in institutionalized elderly people (up to 68%)⁷ than in those living in the community (6%).⁸ The high prevalence among institutionalized patients likely reflects multiple disease processes, including neurologic and cardiac conditions, as well as medications associated with orthostatic hypotension.

CLINICAL MANIFESTATIONS ARE DUE TO HYPOPERFUSION, OVERCOMPENSATION

Symptoms are related to cerebral hypoperfusion, with resulting lack of cerebral oxygenation (causing lightheadedness, dizziness, weakness, difficulty thinking, headache, syncope, or feeling faint) and a compensatory autonomic overreaction (causing palpitations, tremulousness, nausea, coldness of extremities, chest pain, and syncope).

Lightheadedness is a common symptom, but subtler issues such as difficulty thinking, weakness, and neck discomfort are also common in the elderly. Recurrent or unexplained falls in older adults may be a manifestation of syncope due to orthostatic hypotension.

PROGNOSIS DEPENDS ON CAUSE

Orthostatic hypotension is a syndrome, and its prognosis depends on its specific cause, its severity, and the distribution of its autonomic and nonautonomic involvement. In patients who have extrapyramidal and cerebellar disorders (eg, Parkinson disease, multiple system atrophy), the earlier and the more severe the involvement of the autonomic nervous system, the poorer the prognosis.^9,10

In hypertensive patients with diabetes mellitus, the risk of death is higher if they have orthostatic hypotension.¹¹ Diastolic orthostatic hypotension is associated with a higher risk of vascular death in older persons.¹²

MANAGEMENT: FROM A TO F

The goal of management of orthostatic hypotension is to raise the patient’s standing blood pressure without also raising his or her supine blood pressure, and specifically to reduce orthostatic symptoms, increase the time the patient can stand, and improve his or her ability to perform daily activities. No specific treatment is currently available that achieves all these goals, and drugs alone are never completely adequate.

Because the mainstays of treatment are volume expansion and vasoconstriction, it is difficult to improve the symptoms of orthostatic hypotension without inducing some degree of supine hypertension. Strategies to minimize nocturnal hypertension and to treat orthostatic hypotension in special circumstances are summarized in Table 1.

If hypovolemia is playing a major role, and the patient cannot ingest enough salt or plasma volume fails to increase despite salt supplementation, fludrocortisone (Florinef) should be considered. Untreated hypovolemia will decrease the efficacy of vasoconstrictor drugs.

Pyridostigmine (Mestinon) has a putative vasoconstrictor effect only during standing, but because its effect is modest it should be used in mild orthostatic hypotension that does not improve with nonpharmacologic measures and in moderate cases. Its effect can be enhanced with additional low doses of midodrine (ProAmatine). Midodrine with or without fludrocortisone should be used in severe orthostatic hypotension.

A: Abdominal compression

In conditions in which there is adrenergic denervation of vascular beds, there is an increase in vascular capacitance and peripheral venous pooling. Compression of capacitance beds (ie, the legs and abdomen) improves orthostatic symptoms.¹⁴ The improvement is due to a reduction of venous capacitance and an increase in total peripheral resistance.¹⁴

On standing, healthy adults experience an orthostatic shift of approximately 500 mL of blood to the lower extremities¹⁵ that, when added to an increased vascular capacitance in those with orthostatic hypotension, results in a relative state of hypovolemia.

Compression of the legs alone is not as beneficial as compression of the abdomen because the venous capacitance of the calves and thighs is relatively small compared with that of the splanchnic mesenteric bed, which accounts for 20% to 30% of total blood volume.¹⁶ Moreover, compression garments and stockings that are strong enough to produce a measurable effect on orthostatic hypotension are cumbersome to put on and uncomfortable to wear. Because some patients gain significant benefit from abdominal compression alone, this should be considered the first step in reducing venous capacitance.

In a laboratory experiment, Smit et al¹⁷ found that an elastic abdominal binder that exerted 15 to 20 mm Hg of pressure on the abdomen raised the standing blood pressure by about 11/6 mmHg, which was comparable to the effect of a gravity suit (such as those worn by fighter pilots to prevent syncope during violent aircraft maneuvers) inflated to 20 mm Hg—an increase of about 17/8 mm Hg. Higher gravity-suit pressures had a greater effect.

In practical terms, the binder should be tight enough to exert gentle pressure. It should be put on before rising from bed in the morning and taken off when lying supine, to avoid supine hypertension. Advantages are that a binder’s effects are immediate, its benefits can be easily assessed, and it can be used on an as-needed basis by patients who need it only during periods of prolonged orthostatic stress. Binders are also easy to fit and are available in most sporting good stores and on the Web (try searching for “abdominal binder”).

When abdominal compression alone is not enough, the addition of compression of the lower extremities can result in further benefits. This can be achieved by using compression garments that ideally extend to the waist or, at the least, to the proximal thigh.

Rapidly drinking two 8-oz (500-mL) glasses of cold water helps expand plasma volume. It also, within a few minutes, elicits a significant pressor effect that is in part norepinephrine-mediated,^18,19 increasing the standing systolic blood pressure by more than 20 mm Hg for about 2 hours and improving symptoms and orthostatic endurance.^18,20 This easy technique can be used when prolonged standing is expected (eg, shopping).

B (continued): Bed up

The head of the bed of a patient with orthostatic hypotension should be elevated by 10 to 20 degrees or 4 inches (10 cm) to decrease nocturnal hypertension and nocturnal diuresis.²¹ During the day, adequate orthostatic stress, ie, upright activity, should be maintained. If patients are repeatedly tilted up, their orthostatic hypotension is gradually attenuated, presumably by increasing venomotor tone.²²

C: Countermaneuvers

Physical countermaneuvers involve isometrically contracting the muscles below the waist for about 30 seconds at a time, which reduces venous capacitance, increases total peripheral resistance, and augments venous return to the heart.^23,24 These countermeasures can help maintain blood pressure during daily activities and should be considered at the first symptoms of orthostatic intolerance and in situations of orthostatic stress (eg, standing for prolonged periods).

Specific techniques include²³:

• Toe-raising
• Leg-crossing and contraction
• Thigh muscle co-contraction
• Bending at the waist
• Slow marching in place
• Leg elevation.

D: Drugs

Midodrine, a vasopressor, is effective and safe when used for treating neurogenic orthostatic hypotension.²⁵ It has been shown to increase standing systolic blood pressure, reduce orthostatic lightheadedness, and increase standing and walking time.

A common starting dose is 5 mg three times a day; most patients respond best to 10 mg three times a day. As its duration of action is short (2 to 4 hours),^25–27 it should be taken before arising in the morning, before lunch, and in the midafternoon. To avoid nocturnal supine hypertension, doses should not be taken after the midafternoon, and a dose should be omitted if the supine or sitting blood pressure is greater than 180/100 mm Hg.

Midodrine’s main side effects are supine hypertension, scalp paresthesias, and pilomotor reactions (goosebumps). Vasoconstrictors such as midodrine are ineffective when plasma volume is reduced.

Fludrocortisone is a synthetic mineralocorticoid that has a pressor effect as a result of its ability to expand plasma volume and increase vascular alpha-adrenoceptor sensitivity.^28–30 This medication is helpful when plasma volume fails to adequately increase with salt supplementation³¹ and for patients who cannot ingest enough salt or do not respond adequately to midodrine.

The usual dose is 0.1 to 0.2 mg/day, but it may be increased to 0.4 to 0.6 mg/day in patients with refractory orthostatic hypotension.

If the patient gains 3 to 5 pounds (1.2–2.3 kg) and develops mild dependent edema, you can infer that the plasma volume has expanded adequately. However, in view of these effects, fludrocortisone is contraindicated in congestive heart failure and chronic renal failure. The potential risks are severe hypokalemia and excessive supine hypertension. Frequent monitoring of serum potassium, a diet high in potassium, and regular checks of supine blood pressure are advised, especially at higher doses, when added to midodrine, or in elderly patients who tend to poorly tolerate the medication.^28,29,32

Pyridostigmine is a cholinesterase inhibitor that improves ganglionic neurotransmission in the sympathetic baroreflex pathway. Because this pathway is activated primarily during standing, this drug improves orthostatic hypotension and total peripheral resistance without aggravating supine hypertension. Because the pressor effect is modest, it is most adequate for patients with mild to moderate orthostatic hypotension.^33,34

Dosing is started at 30 mg two to three times a day and is gradually increased to 60 mg three times a day. The drug’s effectiveness can be enhanced by combining each dose of pyridostigmine with 5 mg of midodrine without occurrence of supine hypertension.³⁴ Mestinon Timespan, a 180-mg slow-release pyridostigmine tablet, can be taken once a day and may be a convenient alternative.

The main side effects are cholinergic (abdominal colic, diarrhea).

Review the patient’s medications. If he or she is taking any drug that may cause orthostatic hypotension, consider discontinuing it, substituting another drug, or changing the dosage (Table 2). In the elderly, antiparkinsonian, nitrate, antidepressant, diuretic, prostate, and antihypertensive medications³⁵ may be particularly suspect.

E: Education

Education is probably the single most important factor in the proper control of orthostatic hypotension. A number of issues should be considered.

• Patients should be taught, in simple terms, the mechanisms that maintain postural normotension and how to recognize the onset of orthostatic symptoms.
• They must realize that there is no specific treatment of the underlying cause and that drug treatment alone is not adequate.
• They should be taught nonpharmacologic approaches and be aware that other drugs they start may worsen symptoms.

It is also important that the patient learn the conditions (and their mechanisms) that can lower blood pressure (Table 3). Such conditions include prolonged or motionless standing, alcohol ingestion (causing vasodilation), carbohydrate-heavy meals (causing postprandial orthostatic hypotension related to an increase in the splanchnic-mesenteric venous capacitance), early morning orthostatic hypotension related to nocturnal diuresis and arising from bed, physical activity sufficient to cause muscle vasodilation, heat exposure (eg, hot weather or a hot bath or shower) producing skin vessel vasodilation, sudden postural changes, and prolonged recumbency. Once these stressors are explained, patients have no difficulty recognizing them.

The patient should also be instructed in how to manage situations of increased orthostatic stress and periods of orthostatic decompensation, to minimize nocturnal hypertension, and to modify their activities of daily living. Keeping a log of supine and upright blood pressures (taken with an automated sphygmomanometer) during situations of orthostatic stress can help establish whether worsening symptoms are related to orthostatic hypotension or to another mechanism. Once patients discover that they can actively deal with these situations, they develop a great sense of empowerment.

E (continued): Exercise

Mild physical exercise improves orthostatic tolerance by reducing venous pooling and increasing plasma volume.³⁶ Deconditioning from lack of exercise exacerbates orthostatic hypotension.³⁷ Because upright exercise may increase the orthostatic drop in blood pressure, training in a supine or sitting position (eg, swimming, recumbent biking) is advisable. Isotonic exercise (eg, light weight-lifting) is recommended because the incorrect straining and breath-holding during isometric exercise (eg, holding weights in the same position) may decrease venous return.

Maintaining an adequate plasma volume is crucial. Patients should drink five to eight 8-ounce glasses (1.25 to 2.5 L) of water or other fluid per day. Many elderly people do not take in this much. The patient should have at least 1 glass or cup of fluid with meals and at least twice at other times of each day to obtain 1 L/day.

Salt intake should be between 150 and 250 mmol of sodium (10 to 20 g of salt) per day. Sodium helps with retention of ingested fluids and should be maximized if tolerated. However, caution should be exercised in patients who have severe refractory supine hypertension, uncontrolled hypertension, or comorbidities characterized by insterstitial edema (eg, heart failure, liver failure). Some patients are very sensitive to sodium supplementation and can fine-tune their orthostatic control with salt alone. If salting food is not desired, prepared soups, pretzels, potato chips, and 0.5- or 1.0-g salt tablets can be an option.

Patients need to maintain a high-potassium diet, as the high sodium intake combined with fludrocortisone promotes potassium loss. Fruits (especially bananas) and vegetables have high potassium content.

The combination of fludrocortisone and a high-salt diet can also cause sustained supine hypertension, which can be minimized by the interventions noted in Table 2.

Appropriate salt supplementation and fluid intake leading to an adequate volume expansion can be verified by checking the 24-hour urinary sodium content: patients who excrete less than 170 mmol can be treated with 1 to 2 g of supplemental sodium three times a day.³⁸

Orthostatic hypotension is a chronic, debilitating illness associated with common neurologic conditions (eg, diabetic neuropathy, Parkinson disease). It is common in the elderly, especially in those who are institutionalized and are using multiple medications.

Treatment can be challenging, especially if the problem is neurogenic. This condition has no cure, symptoms vary in different circumstances, treatment is nonspecific, and aggressive treatment can lead to marked supine hypertension.

This review focuses on the prevention and treatment of neurogenic causes of orthostatic hypotension. We emphasize a simple but effective patient-oriented approach to management, using a combination of nonpharmacologic strategies and drugs clinically proven to be efficacious. The recommendations and their rationale are organized in a practical and easy-to-remember format for both physicians and patients.

WHAT HAPPENS WHEN WE STAND UP?

When we stand up, the blood goes down from the chest to the distensible venous capacitance system below the diaphragm. This fluid shift produces a decrease in venous return, ventricular filling, cardiac output, and blood pressure.¹

This gravity-induced drop in blood pressure, detected by arterial baroreceptors in the aortic arch and carotid sinus, triggers a compensatory reflex tachycardia and vasoconstriction that restores normotension in the upright position. This compensatory mechanism is termed a baroreflex; it is mediated by afferent and efferent autonomic peripheral nerves and is integrated in autonomic centers in the brainstem.²

Orthostatic hypotension is the result of baroreflex failure (autonomic failure), end-organ dysfunction, or volume depletion. Injury to any limb of the baroreflex causes neurogenic orthostatic hypotension, although with afferent lesions alone, the hypotension tends to be modest and accompanied by wide fluctuations in blood pressure, including severe hypertension. Drugs can produce orthostatic hypotension by interfering with the autonomic pathways or their target end-organs or by affecting intravascular volume. Brain hypoperfusion, resulting from orthostatic hypotension from any cause, can lead to symptoms of orthostatic intolerance (eg, lightheadedness) and falls, and if the hypotension is severe, to syncope.

A DECREASE OF 20 MM HG SYSTOLIC OR 10 MM HG DIASTOLIC

The consensus definition of orthostatic hypotension is a reduction of systolic blood pressure of at least 20 mm Hg or a reduction of diastolic blood pressure of at least 10 mm Hg within 3 minutes of erect standing.³ A transient drop that occurs with abrupt standing and resolves rapidly suggests a benign condition, such as dehydration, rather than autonomic failure.

In the laboratory, patients are placed on a tilt table in the head-up position at an angle of at least 60 degrees to detect orthostatic changes in blood pressure. In the office, 1 minute of standing probably detects nearly all cases of orthostatic hypotension; however, standing beyond 2 minutes helps establish the severity (a further drop in blood pressure).⁴ Orthostatic hypotension developing after 3 minutes of standing is uncommon and may represent a reflex presyncope (eg, vasovagal) or a mild or early form of sympathetic adrenergic dysfunction.^{4, 5}

NEUROGENIC AND NONNEUROGENIC CAUSES

Orthostatic hypotension may result from neurogenic and nonneurogenic causes.

Neurogenic orthostatic hypotension can be due to neuropathy (eg, diabetic or autoimmune neuropathies) or to central lesions (eg, Parkinson disease or multiple system atrophy). Its presence, severity, and temporal course can be important clues in diagnosing Parkinson disease and differentiating it from other parkinsonian syndromes with a more ominous prognosis, such as multiple system atrophy and Lewy body dementia.

Nonneurogenic causes include cardiac impairment (eg, from myocardial infarction or aortic stenosis), reduced intravascular volume (eg, from dehydration, adrenal insufficiency), and vasodilation (eg, from fever, systemic mastocytosis).

Common drugs that cause orthostatic hypotension are diuretics, alpha-adrenoceptor blockers for prostatic hypertrophy, antihypertensive drugs, and calcium channel blockers. Insulin, levodopa, and tricyclic antidepressants can also cause vasodilation and orthostatic hypotension in predisposed patients. Poon and Braun,⁶ in a retrospective study in elderly veterans, identified hydrochlorothiazide, lisinopril (Prinivil, Zestril), trazodone (Desyrel), furosemide (Lasix), and terazosin (Hytrin) as the most common culprits.

ORTHOSTATIC HYPOTENSION IS COMMON IN THE ELDERLY

The prevalence of orthostatic hypotension is high in the elderly and depends on the characteristics of the population studied, such as age, use of medications, and comorbidities known to be associated with this problem. Orthostatic hypotension is more common in institutionalized elderly people (up to 68%)⁷ than in those living in the community (6%).⁸ The high prevalence among institutionalized patients likely reflects multiple disease processes, including neurologic and cardiac conditions, as well as medications associated with orthostatic hypotension.

CLINICAL MANIFESTATIONS ARE DUE TO HYPOPERFUSION, OVERCOMPENSATION

Symptoms are related to cerebral hypoperfusion, with resulting lack of cerebral oxygenation (causing lightheadedness, dizziness, weakness, difficulty thinking, headache, syncope, or feeling faint) and a compensatory autonomic overreaction (causing palpitations, tremulousness, nausea, coldness of extremities, chest pain, and syncope).

Lightheadedness is a common symptom, but subtler issues such as difficulty thinking, weakness, and neck discomfort are also common in the elderly. Recurrent or unexplained falls in older adults may be a manifestation of syncope due to orthostatic hypotension.

PROGNOSIS DEPENDS ON CAUSE

Orthostatic hypotension is a syndrome, and its prognosis depends on its specific cause, its severity, and the distribution of its autonomic and nonautonomic involvement. In patients who have extrapyramidal and cerebellar disorders (eg, Parkinson disease, multiple system atrophy), the earlier and the more severe the involvement of the autonomic nervous system, the poorer the prognosis.^9,10

In hypertensive patients with diabetes mellitus, the risk of death is higher if they have orthostatic hypotension.¹¹ Diastolic orthostatic hypotension is associated with a higher risk of vascular death in older persons.¹²

MANAGEMENT: FROM A TO F

The goal of management of orthostatic hypotension is to raise the patient’s standing blood pressure without also raising his or her supine blood pressure, and specifically to reduce orthostatic symptoms, increase the time the patient can stand, and improve his or her ability to perform daily activities. No specific treatment is currently available that achieves all these goals, and drugs alone are never completely adequate.

Because the mainstays of treatment are volume expansion and vasoconstriction, it is difficult to improve the symptoms of orthostatic hypotension without inducing some degree of supine hypertension. Strategies to minimize nocturnal hypertension and to treat orthostatic hypotension in special circumstances are summarized in Table 1.

If hypovolemia is playing a major role, and the patient cannot ingest enough salt or plasma volume fails to increase despite salt supplementation, fludrocortisone (Florinef) should be considered. Untreated hypovolemia will decrease the efficacy of vasoconstrictor drugs.

Pyridostigmine (Mestinon) has a putative vasoconstrictor effect only during standing, but because its effect is modest it should be used in mild orthostatic hypotension that does not improve with nonpharmacologic measures and in moderate cases. Its effect can be enhanced with additional low doses of midodrine (ProAmatine). Midodrine with or without fludrocortisone should be used in severe orthostatic hypotension.

A: Abdominal compression

In conditions in which there is adrenergic denervation of vascular beds, there is an increase in vascular capacitance and peripheral venous pooling. Compression of capacitance beds (ie, the legs and abdomen) improves orthostatic symptoms.¹⁴ The improvement is due to a reduction of venous capacitance and an increase in total peripheral resistance.¹⁴

On standing, healthy adults experience an orthostatic shift of approximately 500 mL of blood to the lower extremities¹⁵ that, when added to an increased vascular capacitance in those with orthostatic hypotension, results in a relative state of hypovolemia.

Compression of the legs alone is not as beneficial as compression of the abdomen because the venous capacitance of the calves and thighs is relatively small compared with that of the splanchnic mesenteric bed, which accounts for 20% to 30% of total blood volume.¹⁶ Moreover, compression garments and stockings that are strong enough to produce a measurable effect on orthostatic hypotension are cumbersome to put on and uncomfortable to wear. Because some patients gain significant benefit from abdominal compression alone, this should be considered the first step in reducing venous capacitance.

In a laboratory experiment, Smit et al¹⁷ found that an elastic abdominal binder that exerted 15 to 20 mm Hg of pressure on the abdomen raised the standing blood pressure by about 11/6 mmHg, which was comparable to the effect of a gravity suit (such as those worn by fighter pilots to prevent syncope during violent aircraft maneuvers) inflated to 20 mm Hg—an increase of about 17/8 mm Hg. Higher gravity-suit pressures had a greater effect.

In practical terms, the binder should be tight enough to exert gentle pressure. It should be put on before rising from bed in the morning and taken off when lying supine, to avoid supine hypertension. Advantages are that a binder’s effects are immediate, its benefits can be easily assessed, and it can be used on an as-needed basis by patients who need it only during periods of prolonged orthostatic stress. Binders are also easy to fit and are available in most sporting good stores and on the Web (try searching for “abdominal binder”).

When abdominal compression alone is not enough, the addition of compression of the lower extremities can result in further benefits. This can be achieved by using compression garments that ideally extend to the waist or, at the least, to the proximal thigh.

Rapidly drinking two 8-oz (500-mL) glasses of cold water helps expand plasma volume. It also, within a few minutes, elicits a significant pressor effect that is in part norepinephrine-mediated,^18,19 increasing the standing systolic blood pressure by more than 20 mm Hg for about 2 hours and improving symptoms and orthostatic endurance.^18,20 This easy technique can be used when prolonged standing is expected (eg, shopping).

B (continued): Bed up

The head of the bed of a patient with orthostatic hypotension should be elevated by 10 to 20 degrees or 4 inches (10 cm) to decrease nocturnal hypertension and nocturnal diuresis.²¹ During the day, adequate orthostatic stress, ie, upright activity, should be maintained. If patients are repeatedly tilted up, their orthostatic hypotension is gradually attenuated, presumably by increasing venomotor tone.²²

C: Countermaneuvers

Physical countermaneuvers involve isometrically contracting the muscles below the waist for about 30 seconds at a time, which reduces venous capacitance, increases total peripheral resistance, and augments venous return to the heart.^23,24 These countermeasures can help maintain blood pressure during daily activities and should be considered at the first symptoms of orthostatic intolerance and in situations of orthostatic stress (eg, standing for prolonged periods).

Specific techniques include²³:

• Toe-raising
• Leg-crossing and contraction
• Thigh muscle co-contraction
• Bending at the waist
• Slow marching in place
• Leg elevation.

D: Drugs

Midodrine, a vasopressor, is effective and safe when used for treating neurogenic orthostatic hypotension.²⁵ It has been shown to increase standing systolic blood pressure, reduce orthostatic lightheadedness, and increase standing and walking time.

A common starting dose is 5 mg three times a day; most patients respond best to 10 mg three times a day. As its duration of action is short (2 to 4 hours),^25–27 it should be taken before arising in the morning, before lunch, and in the midafternoon. To avoid nocturnal supine hypertension, doses should not be taken after the midafternoon, and a dose should be omitted if the supine or sitting blood pressure is greater than 180/100 mm Hg.

Midodrine’s main side effects are supine hypertension, scalp paresthesias, and pilomotor reactions (goosebumps). Vasoconstrictors such as midodrine are ineffective when plasma volume is reduced.

Fludrocortisone is a synthetic mineralocorticoid that has a pressor effect as a result of its ability to expand plasma volume and increase vascular alpha-adrenoceptor sensitivity.^28–30 This medication is helpful when plasma volume fails to adequately increase with salt supplementation³¹ and for patients who cannot ingest enough salt or do not respond adequately to midodrine.

The usual dose is 0.1 to 0.2 mg/day, but it may be increased to 0.4 to 0.6 mg/day in patients with refractory orthostatic hypotension.

If the patient gains 3 to 5 pounds (1.2–2.3 kg) and develops mild dependent edema, you can infer that the plasma volume has expanded adequately. However, in view of these effects, fludrocortisone is contraindicated in congestive heart failure and chronic renal failure. The potential risks are severe hypokalemia and excessive supine hypertension. Frequent monitoring of serum potassium, a diet high in potassium, and regular checks of supine blood pressure are advised, especially at higher doses, when added to midodrine, or in elderly patients who tend to poorly tolerate the medication.^28,29,32

Pyridostigmine is a cholinesterase inhibitor that improves ganglionic neurotransmission in the sympathetic baroreflex pathway. Because this pathway is activated primarily during standing, this drug improves orthostatic hypotension and total peripheral resistance without aggravating supine hypertension. Because the pressor effect is modest, it is most adequate for patients with mild to moderate orthostatic hypotension.^33,34

Dosing is started at 30 mg two to three times a day and is gradually increased to 60 mg three times a day. The drug’s effectiveness can be enhanced by combining each dose of pyridostigmine with 5 mg of midodrine without occurrence of supine hypertension.³⁴ Mestinon Timespan, a 180-mg slow-release pyridostigmine tablet, can be taken once a day and may be a convenient alternative.

The main side effects are cholinergic (abdominal colic, diarrhea).

Review the patient’s medications. If he or she is taking any drug that may cause orthostatic hypotension, consider discontinuing it, substituting another drug, or changing the dosage (Table 2). In the elderly, antiparkinsonian, nitrate, antidepressant, diuretic, prostate, and antihypertensive medications³⁵ may be particularly suspect.

E: Education

Education is probably the single most important factor in the proper control of orthostatic hypotension. A number of issues should be considered.

• Patients should be taught, in simple terms, the mechanisms that maintain postural normotension and how to recognize the onset of orthostatic symptoms.
• They must realize that there is no specific treatment of the underlying cause and that drug treatment alone is not adequate.
• They should be taught nonpharmacologic approaches and be aware that other drugs they start may worsen symptoms.

It is also important that the patient learn the conditions (and their mechanisms) that can lower blood pressure (Table 3). Such conditions include prolonged or motionless standing, alcohol ingestion (causing vasodilation), carbohydrate-heavy meals (causing postprandial orthostatic hypotension related to an increase in the splanchnic-mesenteric venous capacitance), early morning orthostatic hypotension related to nocturnal diuresis and arising from bed, physical activity sufficient to cause muscle vasodilation, heat exposure (eg, hot weather or a hot bath or shower) producing skin vessel vasodilation, sudden postural changes, and prolonged recumbency. Once these stressors are explained, patients have no difficulty recognizing them.

The patient should also be instructed in how to manage situations of increased orthostatic stress and periods of orthostatic decompensation, to minimize nocturnal hypertension, and to modify their activities of daily living. Keeping a log of supine and upright blood pressures (taken with an automated sphygmomanometer) during situations of orthostatic stress can help establish whether worsening symptoms are related to orthostatic hypotension or to another mechanism. Once patients discover that they can actively deal with these situations, they develop a great sense of empowerment.

E (continued): Exercise

Mild physical exercise improves orthostatic tolerance by reducing venous pooling and increasing plasma volume.³⁶ Deconditioning from lack of exercise exacerbates orthostatic hypotension.³⁷ Because upright exercise may increase the orthostatic drop in blood pressure, training in a supine or sitting position (eg, swimming, recumbent biking) is advisable. Isotonic exercise (eg, light weight-lifting) is recommended because the incorrect straining and breath-holding during isometric exercise (eg, holding weights in the same position) may decrease venous return.

Maintaining an adequate plasma volume is crucial. Patients should drink five to eight 8-ounce glasses (1.25 to 2.5 L) of water or other fluid per day. Many elderly people do not take in this much. The patient should have at least 1 glass or cup of fluid with meals and at least twice at other times of each day to obtain 1 L/day.

Salt intake should be between 150 and 250 mmol of sodium (10 to 20 g of salt) per day. Sodium helps with retention of ingested fluids and should be maximized if tolerated. However, caution should be exercised in patients who have severe refractory supine hypertension, uncontrolled hypertension, or comorbidities characterized by insterstitial edema (eg, heart failure, liver failure). Some patients are very sensitive to sodium supplementation and can fine-tune their orthostatic control with salt alone. If salting food is not desired, prepared soups, pretzels, potato chips, and 0.5- or 1.0-g salt tablets can be an option.

Patients need to maintain a high-potassium diet, as the high sodium intake combined with fludrocortisone promotes potassium loss. Fruits (especially bananas) and vegetables have high potassium content.

The combination of fludrocortisone and a high-salt diet can also cause sustained supine hypertension, which can be minimized by the interventions noted in Table 2.

Appropriate salt supplementation and fluid intake leading to an adequate volume expansion can be verified by checking the 24-hour urinary sodium content: patients who excrete less than 170 mmol can be treated with 1 to 2 g of supplemental sodium three times a day.³⁸

Orthostatic hypotension is a chronic, debilitating illness associated with common neurologic conditions (eg, diabetic neuropathy, Parkinson disease). It is common in the elderly, especially in those who are institutionalized and are using multiple medications.

Treatment can be challenging, especially if the problem is neurogenic. This condition has no cure, symptoms vary in different circumstances, treatment is nonspecific, and aggressive treatment can lead to marked supine hypertension.

This review focuses on the prevention and treatment of neurogenic causes of orthostatic hypotension. We emphasize a simple but effective patient-oriented approach to management, using a combination of nonpharmacologic strategies and drugs clinically proven to be efficacious. The recommendations and their rationale are organized in a practical and easy-to-remember format for both physicians and patients.

WHAT HAPPENS WHEN WE STAND UP?

When we stand up, the blood goes down from the chest to the distensible venous capacitance system below the diaphragm. This fluid shift produces a decrease in venous return, ventricular filling, cardiac output, and blood pressure.¹

This gravity-induced drop in blood pressure, detected by arterial baroreceptors in the aortic arch and carotid sinus, triggers a compensatory reflex tachycardia and vasoconstriction that restores normotension in the upright position. This compensatory mechanism is termed a baroreflex; it is mediated by afferent and efferent autonomic peripheral nerves and is integrated in autonomic centers in the brainstem.²

Orthostatic hypotension is the result of baroreflex failure (autonomic failure), end-organ dysfunction, or volume depletion. Injury to any limb of the baroreflex causes neurogenic orthostatic hypotension, although with afferent lesions alone, the hypotension tends to be modest and accompanied by wide fluctuations in blood pressure, including severe hypertension. Drugs can produce orthostatic hypotension by interfering with the autonomic pathways or their target end-organs or by affecting intravascular volume. Brain hypoperfusion, resulting from orthostatic hypotension from any cause, can lead to symptoms of orthostatic intolerance (eg, lightheadedness) and falls, and if the hypotension is severe, to syncope.

A DECREASE OF 20 MM HG SYSTOLIC OR 10 MM HG DIASTOLIC

The consensus definition of orthostatic hypotension is a reduction of systolic blood pressure of at least 20 mm Hg or a reduction of diastolic blood pressure of at least 10 mm Hg within 3 minutes of erect standing.³ A transient drop that occurs with abrupt standing and resolves rapidly suggests a benign condition, such as dehydration, rather than autonomic failure.

In the laboratory, patients are placed on a tilt table in the head-up position at an angle of at least 60 degrees to detect orthostatic changes in blood pressure. In the office, 1 minute of standing probably detects nearly all cases of orthostatic hypotension; however, standing beyond 2 minutes helps establish the severity (a further drop in blood pressure).⁴ Orthostatic hypotension developing after 3 minutes of standing is uncommon and may represent a reflex presyncope (eg, vasovagal) or a mild or early form of sympathetic adrenergic dysfunction.^{4, 5}

NEUROGENIC AND NONNEUROGENIC CAUSES

Orthostatic hypotension may result from neurogenic and nonneurogenic causes.

Neurogenic orthostatic hypotension can be due to neuropathy (eg, diabetic or autoimmune neuropathies) or to central lesions (eg, Parkinson disease or multiple system atrophy). Its presence, severity, and temporal course can be important clues in diagnosing Parkinson disease and differentiating it from other parkinsonian syndromes with a more ominous prognosis, such as multiple system atrophy and Lewy body dementia.

Nonneurogenic causes include cardiac impairment (eg, from myocardial infarction or aortic stenosis), reduced intravascular volume (eg, from dehydration, adrenal insufficiency), and vasodilation (eg, from fever, systemic mastocytosis).

Common drugs that cause orthostatic hypotension are diuretics, alpha-adrenoceptor blockers for prostatic hypertrophy, antihypertensive drugs, and calcium channel blockers. Insulin, levodopa, and tricyclic antidepressants can also cause vasodilation and orthostatic hypotension in predisposed patients. Poon and Braun,⁶ in a retrospective study in elderly veterans, identified hydrochlorothiazide, lisinopril (Prinivil, Zestril), trazodone (Desyrel), furosemide (Lasix), and terazosin (Hytrin) as the most common culprits.

ORTHOSTATIC HYPOTENSION IS COMMON IN THE ELDERLY

The prevalence of orthostatic hypotension is high in the elderly and depends on the characteristics of the population studied, such as age, use of medications, and comorbidities known to be associated with this problem. Orthostatic hypotension is more common in institutionalized elderly people (up to 68%)⁷ than in those living in the community (6%).⁸ The high prevalence among institutionalized patients likely reflects multiple disease processes, including neurologic and cardiac conditions, as well as medications associated with orthostatic hypotension.

CLINICAL MANIFESTATIONS ARE DUE TO HYPOPERFUSION, OVERCOMPENSATION

Symptoms are related to cerebral hypoperfusion, with resulting lack of cerebral oxygenation (causing lightheadedness, dizziness, weakness, difficulty thinking, headache, syncope, or feeling faint) and a compensatory autonomic overreaction (causing palpitations, tremulousness, nausea, coldness of extremities, chest pain, and syncope).

Lightheadedness is a common symptom, but subtler issues such as difficulty thinking, weakness, and neck discomfort are also common in the elderly. Recurrent or unexplained falls in older adults may be a manifestation of syncope due to orthostatic hypotension.

PROGNOSIS DEPENDS ON CAUSE

Orthostatic hypotension is a syndrome, and its prognosis depends on its specific cause, its severity, and the distribution of its autonomic and nonautonomic involvement. In patients who have extrapyramidal and cerebellar disorders (eg, Parkinson disease, multiple system atrophy), the earlier and the more severe the involvement of the autonomic nervous system, the poorer the prognosis.^9,10

In hypertensive patients with diabetes mellitus, the risk of death is higher if they have orthostatic hypotension.¹¹ Diastolic orthostatic hypotension is associated with a higher risk of vascular death in older persons.¹²

MANAGEMENT: FROM A TO F

The goal of management of orthostatic hypotension is to raise the patient’s standing blood pressure without also raising his or her supine blood pressure, and specifically to reduce orthostatic symptoms, increase the time the patient can stand, and improve his or her ability to perform daily activities. No specific treatment is currently available that achieves all these goals, and drugs alone are never completely adequate.

Because the mainstays of treatment are volume expansion and vasoconstriction, it is difficult to improve the symptoms of orthostatic hypotension without inducing some degree of supine hypertension. Strategies to minimize nocturnal hypertension and to treat orthostatic hypotension in special circumstances are summarized in Table 1.

If hypovolemia is playing a major role, and the patient cannot ingest enough salt or plasma volume fails to increase despite salt supplementation, fludrocortisone (Florinef) should be considered. Untreated hypovolemia will decrease the efficacy of vasoconstrictor drugs.

Pyridostigmine (Mestinon) has a putative vasoconstrictor effect only during standing, but because its effect is modest it should be used in mild orthostatic hypotension that does not improve with nonpharmacologic measures and in moderate cases. Its effect can be enhanced with additional low doses of midodrine (ProAmatine). Midodrine with or without fludrocortisone should be used in severe orthostatic hypotension.

A: Abdominal compression

In conditions in which there is adrenergic denervation of vascular beds, there is an increase in vascular capacitance and peripheral venous pooling. Compression of capacitance beds (ie, the legs and abdomen) improves orthostatic symptoms.¹⁴ The improvement is due to a reduction of venous capacitance and an increase in total peripheral resistance.¹⁴

On standing, healthy adults experience an orthostatic shift of approximately 500 mL of blood to the lower extremities¹⁵ that, when added to an increased vascular capacitance in those with orthostatic hypotension, results in a relative state of hypovolemia.

Compression of the legs alone is not as beneficial as compression of the abdomen because the venous capacitance of the calves and thighs is relatively small compared with that of the splanchnic mesenteric bed, which accounts for 20% to 30% of total blood volume.¹⁶ Moreover, compression garments and stockings that are strong enough to produce a measurable effect on orthostatic hypotension are cumbersome to put on and uncomfortable to wear. Because some patients gain significant benefit from abdominal compression alone, this should be considered the first step in reducing venous capacitance.

In a laboratory experiment, Smit et al¹⁷ found that an elastic abdominal binder that exerted 15 to 20 mm Hg of pressure on the abdomen raised the standing blood pressure by about 11/6 mmHg, which was comparable to the effect of a gravity suit (such as those worn by fighter pilots to prevent syncope during violent aircraft maneuvers) inflated to 20 mm Hg—an increase of about 17/8 mm Hg. Higher gravity-suit pressures had a greater effect.

In practical terms, the binder should be tight enough to exert gentle pressure. It should be put on before rising from bed in the morning and taken off when lying supine, to avoid supine hypertension. Advantages are that a binder’s effects are immediate, its benefits can be easily assessed, and it can be used on an as-needed basis by patients who need it only during periods of prolonged orthostatic stress. Binders are also easy to fit and are available in most sporting good stores and on the Web (try searching for “abdominal binder”).

When abdominal compression alone is not enough, the addition of compression of the lower extremities can result in further benefits. This can be achieved by using compression garments that ideally extend to the waist or, at the least, to the proximal thigh.

Rapidly drinking two 8-oz (500-mL) glasses of cold water helps expand plasma volume. It also, within a few minutes, elicits a significant pressor effect that is in part norepinephrine-mediated,^18,19 increasing the standing systolic blood pressure by more than 20 mm Hg for about 2 hours and improving symptoms and orthostatic endurance.^18,20 This easy technique can be used when prolonged standing is expected (eg, shopping).

B (continued): Bed up

The head of the bed of a patient with orthostatic hypotension should be elevated by 10 to 20 degrees or 4 inches (10 cm) to decrease nocturnal hypertension and nocturnal diuresis.²¹ During the day, adequate orthostatic stress, ie, upright activity, should be maintained. If patients are repeatedly tilted up, their orthostatic hypotension is gradually attenuated, presumably by increasing venomotor tone.²²

C: Countermaneuvers

Physical countermaneuvers involve isometrically contracting the muscles below the waist for about 30 seconds at a time, which reduces venous capacitance, increases total peripheral resistance, and augments venous return to the heart.^23,24 These countermeasures can help maintain blood pressure during daily activities and should be considered at the first symptoms of orthostatic intolerance and in situations of orthostatic stress (eg, standing for prolonged periods).

Specific techniques include²³:

• Toe-raising
• Leg-crossing and contraction
• Thigh muscle co-contraction
• Bending at the waist
• Slow marching in place
• Leg elevation.

D: Drugs

Midodrine, a vasopressor, is effective and safe when used for treating neurogenic orthostatic hypotension.²⁵ It has been shown to increase standing systolic blood pressure, reduce orthostatic lightheadedness, and increase standing and walking time.

A common starting dose is 5 mg three times a day; most patients respond best to 10 mg three times a day. As its duration of action is short (2 to 4 hours),^25–27 it should be taken before arising in the morning, before lunch, and in the midafternoon. To avoid nocturnal supine hypertension, doses should not be taken after the midafternoon, and a dose should be omitted if the supine or sitting blood pressure is greater than 180/100 mm Hg.

Midodrine’s main side effects are supine hypertension, scalp paresthesias, and pilomotor reactions (goosebumps). Vasoconstrictors such as midodrine are ineffective when plasma volume is reduced.

Fludrocortisone is a synthetic mineralocorticoid that has a pressor effect as a result of its ability to expand plasma volume and increase vascular alpha-adrenoceptor sensitivity.^28–30 This medication is helpful when plasma volume fails to adequately increase with salt supplementation³¹ and for patients who cannot ingest enough salt or do not respond adequately to midodrine.

The usual dose is 0.1 to 0.2 mg/day, but it may be increased to 0.4 to 0.6 mg/day in patients with refractory orthostatic hypotension.

If the patient gains 3 to 5 pounds (1.2–2.3 kg) and develops mild dependent edema, you can infer that the plasma volume has expanded adequately. However, in view of these effects, fludrocortisone is contraindicated in congestive heart failure and chronic renal failure. The potential risks are severe hypokalemia and excessive supine hypertension. Frequent monitoring of serum potassium, a diet high in potassium, and regular checks of supine blood pressure are advised, especially at higher doses, when added to midodrine, or in elderly patients who tend to poorly tolerate the medication.^28,29,32

Pyridostigmine is a cholinesterase inhibitor that improves ganglionic neurotransmission in the sympathetic baroreflex pathway. Because this pathway is activated primarily during standing, this drug improves orthostatic hypotension and total peripheral resistance without aggravating supine hypertension. Because the pressor effect is modest, it is most adequate for patients with mild to moderate orthostatic hypotension.^33,34

Dosing is started at 30 mg two to three times a day and is gradually increased to 60 mg three times a day. The drug’s effectiveness can be enhanced by combining each dose of pyridostigmine with 5 mg of midodrine without occurrence of supine hypertension.³⁴ Mestinon Timespan, a 180-mg slow-release pyridostigmine tablet, can be taken once a day and may be a convenient alternative.

The main side effects are cholinergic (abdominal colic, diarrhea).

Review the patient’s medications. If he or she is taking any drug that may cause orthostatic hypotension, consider discontinuing it, substituting another drug, or changing the dosage (Table 2). In the elderly, antiparkinsonian, nitrate, antidepressant, diuretic, prostate, and antihypertensive medications³⁵ may be particularly suspect.

E: Education

Education is probably the single most important factor in the proper control of orthostatic hypotension. A number of issues should be considered.

• Patients should be taught, in simple terms, the mechanisms that maintain postural normotension and how to recognize the onset of orthostatic symptoms.
• They must realize that there is no specific treatment of the underlying cause and that drug treatment alone is not adequate.
• They should be taught nonpharmacologic approaches and be aware that other drugs they start may worsen symptoms.

It is also important that the patient learn the conditions (and their mechanisms) that can lower blood pressure (Table 3). Such conditions include prolonged or motionless standing, alcohol ingestion (causing vasodilation), carbohydrate-heavy meals (causing postprandial orthostatic hypotension related to an increase in the splanchnic-mesenteric venous capacitance), early morning orthostatic hypotension related to nocturnal diuresis and arising from bed, physical activity sufficient to cause muscle vasodilation, heat exposure (eg, hot weather or a hot bath or shower) producing skin vessel vasodilation, sudden postural changes, and prolonged recumbency. Once these stressors are explained, patients have no difficulty recognizing them.

The patient should also be instructed in how to manage situations of increased orthostatic stress and periods of orthostatic decompensation, to minimize nocturnal hypertension, and to modify their activities of daily living. Keeping a log of supine and upright blood pressures (taken with an automated sphygmomanometer) during situations of orthostatic stress can help establish whether worsening symptoms are related to orthostatic hypotension or to another mechanism. Once patients discover that they can actively deal with these situations, they develop a great sense of empowerment.

E (continued): Exercise

Mild physical exercise improves orthostatic tolerance by reducing venous pooling and increasing plasma volume.³⁶ Deconditioning from lack of exercise exacerbates orthostatic hypotension.³⁷ Because upright exercise may increase the orthostatic drop in blood pressure, training in a supine or sitting position (eg, swimming, recumbent biking) is advisable. Isotonic exercise (eg, light weight-lifting) is recommended because the incorrect straining and breath-holding during isometric exercise (eg, holding weights in the same position) may decrease venous return.

Maintaining an adequate plasma volume is crucial. Patients should drink five to eight 8-ounce glasses (1.25 to 2.5 L) of water or other fluid per day. Many elderly people do not take in this much. The patient should have at least 1 glass or cup of fluid with meals and at least twice at other times of each day to obtain 1 L/day.

Salt intake should be between 150 and 250 mmol of sodium (10 to 20 g of salt) per day. Sodium helps with retention of ingested fluids and should be maximized if tolerated. However, caution should be exercised in patients who have severe refractory supine hypertension, uncontrolled hypertension, or comorbidities characterized by insterstitial edema (eg, heart failure, liver failure). Some patients are very sensitive to sodium supplementation and can fine-tune their orthostatic control with salt alone. If salting food is not desired, prepared soups, pretzels, potato chips, and 0.5- or 1.0-g salt tablets can be an option.

Patients need to maintain a high-potassium diet, as the high sodium intake combined with fludrocortisone promotes potassium loss. Fruits (especially bananas) and vegetables have high potassium content.

The combination of fludrocortisone and a high-salt diet can also cause sustained supine hypertension, which can be minimized by the interventions noted in Table 2.

Appropriate salt supplementation and fluid intake leading to an adequate volume expansion can be verified by checking the 24-hour urinary sodium content: patients who excrete less than 170 mmol can be treated with 1 to 2 g of supplemental sodium three times a day.³⁸

An 85-year-old woman presented to the emergency department with a 2-hour history of dyspnea, dizziness, generalized weakness, nausea, and diaphoresis. Her medical history included hypertension, end-stage renal disease with hemodialysis, and atrial fibrillation.

She had an arteriovenous fistula for dialysis access in her right upper arm, with erythema around the site.

Her creatine kinase level was 1,434 U/L (normal range 30–220), creatine kinase MB 143.4 ng/mL (0.0–8.8 ng/mL), and troponin T 0.1 ng/mL (0.0–0.1 ng/mL). She had ST elevation in leads I and aVL. She was taken for emergency cardiac catheterization.

Three blood cultures were drawn on the day of cardiac catheterization. Two grew gram-positive organisms: one grew coagulase-negative Staphylococcus, and the other grew gram-positive bacilli (anaerobic, non-sporeforming). On the basis of these findings, intravenous vancomycin (Vancocin) was started. Seventy-two hours later, one of two blood cultures again grew coagulase-negative Staphylococcus. Five days after the start of antibiotic treatment, blood cultures were negative, and the patient received intravenous vancomycin for 4 weeks (from the time the blood cultures became negative) for native mitral valve endocarditis.

EMBOLISM AND ENDOCARDITIS: KEY FEATURES

An embolic event occurs in 22% to 50% of cases of infective endocarditis and can involve the lungs, bowel, other organs, or extremities.¹ The incidence of embolization of the coronary arteries in patients with infective endocarditis is unknown, but in one case series² it occurred in 8 (7.5%) of 107 cases. The most common site of coronary embolism is the LAD.³

Myocardial infarction is a rare complication of coronary artery embolization.² It was reported in 17 (2.9%) of 586 consecutive patients with infective endocarditis.⁴ In patients with infectious endocarditis complicated by myocardial infarction, the death rate was nearly double that seen in patients with infective endocarditis without myocardial infarction (64% vs 33%).⁴

TREATMENT

The best treatment for this complication of infective endocarditis is not known, as it has not been well studied. The high death rate in these patients makes restoration of coronary perfusion essential.

Thrombolytics are usually avoided in patients with septic embolization because of concerns about concurrent intracerebral mycotic aneurysms and the risk of hemorrhage.

Percutaneous transluminal angioplasty carries a risk of distal mobilization of emboli, development of mycotic aneurysm at the balloon dilation site, or reocclusion due to a mobile embolus.⁵ Stent placement may improve vessel patency but carries a theoretic risk of infection in bacteremic patients. Percutaneous embolectomy has also been used either prior to or instead of stent placement.⁶ Surgical options include embolectomy in patients who may require surgery, and coronary artery bypass grafting for patients with chronic embolization.⁷

An 85-year-old woman presented to the emergency department with a 2-hour history of dyspnea, dizziness, generalized weakness, nausea, and diaphoresis. Her medical history included hypertension, end-stage renal disease with hemodialysis, and atrial fibrillation.

She had an arteriovenous fistula for dialysis access in her right upper arm, with erythema around the site.

Her creatine kinase level was 1,434 U/L (normal range 30–220), creatine kinase MB 143.4 ng/mL (0.0–8.8 ng/mL), and troponin T 0.1 ng/mL (0.0–0.1 ng/mL). She had ST elevation in leads I and aVL. She was taken for emergency cardiac catheterization.

Three blood cultures were drawn on the day of cardiac catheterization. Two grew gram-positive organisms: one grew coagulase-negative Staphylococcus, and the other grew gram-positive bacilli (anaerobic, non-sporeforming). On the basis of these findings, intravenous vancomycin (Vancocin) was started. Seventy-two hours later, one of two blood cultures again grew coagulase-negative Staphylococcus. Five days after the start of antibiotic treatment, blood cultures were negative, and the patient received intravenous vancomycin for 4 weeks (from the time the blood cultures became negative) for native mitral valve endocarditis.

EMBOLISM AND ENDOCARDITIS: KEY FEATURES

An embolic event occurs in 22% to 50% of cases of infective endocarditis and can involve the lungs, bowel, other organs, or extremities.¹ The incidence of embolization of the coronary arteries in patients with infective endocarditis is unknown, but in one case series² it occurred in 8 (7.5%) of 107 cases. The most common site of coronary embolism is the LAD.³

Myocardial infarction is a rare complication of coronary artery embolization.² It was reported in 17 (2.9%) of 586 consecutive patients with infective endocarditis.⁴ In patients with infectious endocarditis complicated by myocardial infarction, the death rate was nearly double that seen in patients with infective endocarditis without myocardial infarction (64% vs 33%).⁴

TREATMENT

The best treatment for this complication of infective endocarditis is not known, as it has not been well studied. The high death rate in these patients makes restoration of coronary perfusion essential.

Thrombolytics are usually avoided in patients with septic embolization because of concerns about concurrent intracerebral mycotic aneurysms and the risk of hemorrhage.

Percutaneous transluminal angioplasty carries a risk of distal mobilization of emboli, development of mycotic aneurysm at the balloon dilation site, or reocclusion due to a mobile embolus.⁵ Stent placement may improve vessel patency but carries a theoretic risk of infection in bacteremic patients. Percutaneous embolectomy has also been used either prior to or instead of stent placement.⁶ Surgical options include embolectomy in patients who may require surgery, and coronary artery bypass grafting for patients with chronic embolization.⁷

An 85-year-old woman presented to the emergency department with a 2-hour history of dyspnea, dizziness, generalized weakness, nausea, and diaphoresis. Her medical history included hypertension, end-stage renal disease with hemodialysis, and atrial fibrillation.

She had an arteriovenous fistula for dialysis access in her right upper arm, with erythema around the site.

Her creatine kinase level was 1,434 U/L (normal range 30–220), creatine kinase MB 143.4 ng/mL (0.0–8.8 ng/mL), and troponin T 0.1 ng/mL (0.0–0.1 ng/mL). She had ST elevation in leads I and aVL. She was taken for emergency cardiac catheterization.

Three blood cultures were drawn on the day of cardiac catheterization. Two grew gram-positive organisms: one grew coagulase-negative Staphylococcus, and the other grew gram-positive bacilli (anaerobic, non-sporeforming). On the basis of these findings, intravenous vancomycin (Vancocin) was started. Seventy-two hours later, one of two blood cultures again grew coagulase-negative Staphylococcus. Five days after the start of antibiotic treatment, blood cultures were negative, and the patient received intravenous vancomycin for 4 weeks (from the time the blood cultures became negative) for native mitral valve endocarditis.

EMBOLISM AND ENDOCARDITIS: KEY FEATURES

An embolic event occurs in 22% to 50% of cases of infective endocarditis and can involve the lungs, bowel, other organs, or extremities.¹ The incidence of embolization of the coronary arteries in patients with infective endocarditis is unknown, but in one case series² it occurred in 8 (7.5%) of 107 cases. The most common site of coronary embolism is the LAD.³

Myocardial infarction is a rare complication of coronary artery embolization.² It was reported in 17 (2.9%) of 586 consecutive patients with infective endocarditis.⁴ In patients with infectious endocarditis complicated by myocardial infarction, the death rate was nearly double that seen in patients with infective endocarditis without myocardial infarction (64% vs 33%).⁴

TREATMENT

The best treatment for this complication of infective endocarditis is not known, as it has not been well studied. The high death rate in these patients makes restoration of coronary perfusion essential.

Thrombolytics are usually avoided in patients with septic embolization because of concerns about concurrent intracerebral mycotic aneurysms and the risk of hemorrhage.

Percutaneous transluminal angioplasty carries a risk of distal mobilization of emboli, development of mycotic aneurysm at the balloon dilation site, or reocclusion due to a mobile embolus.⁵ Stent placement may improve vessel patency but carries a theoretic risk of infection in bacteremic patients. Percutaneous embolectomy has also been used either prior to or instead of stent placement.⁶ Surgical options include embolectomy in patients who may require surgery, and coronary artery bypass grafting for patients with chronic embolization.⁷

Vitamin D deficiency may play a role in the pathogenesis of chronic heart failure, but whether giving patients supplements to raise their vitamin D levels into the normal range improves their survival is not clear.

ASSOCIATION BETWEEN VITAMIN D DEFICIENCY AND OTHER DISORDERS

In the mid-17th century, Whistler and Glisson independently described rickets as a severe bone-deforming disease characterized by growth retardation, bending of the spine, deformities of the legs, and weak and toneless muscles. Histologically, rickets is characterized by impaired mineralization of the cartilage in the epiphyseal growth plates in children. In 1919, Sir Edward Mellanby identified vitamin D deficiency as the cause.

Osteomalacia, another disease caused by vitamin D deficiency, is a disorder of mineralization of newly formed bone matrix in adults. Vitamin D, therefore, has well-known roles in maintaining bone health and calcium and phosphorus homeostasis.

In addition, vitamin D deficiency has been shown in recent years to be associated with myocardial dysfunction.^1,2

VITAMIN D METABOLISM IS COMPLEX

In skin exposed to ultraviolet B light, the provitamin 7-dehydrocholesterol is converted to vitamin D₃ (cholecalciferol). Vitamin D₃ is also obtained from dietary sources. However, many scientists consider vitamin D more a hormone than a classic vitamin, as adequate exposure to sunlight may negate the need for dietary supplements.

The active form of vitamin D is synthesized by hydroxylation in the liver and kidney. In the liver, hepatic enzymes add a hydroxyl (OH) group to vitamin D₃, changing it to 25-hydroxyvitamin D₃. In the kidney, 25-hydroxyvitamin D₃ receives another hydroxyl group, converting it to the biologically active metabolite 1,25-dihydroxyvitamin D₃ (calcitriol). This renal hydroxylation is via 1-alpha-hydroxylase activity and is directly under control of parathyroid hormone (PTH), and indirectly under control of the serum concentrations of calcium.

Interestingly, a number of different organ cells, including cardiomyocytes, also express 1-alpha-hydroxylase and therefore also convert 25-hydroxyvitamin D₃ to 1,25-dihydroxyvitamin D₃. Unlike the renal hydroxylation, this extrarenal process depends on cytokine activation and on serum levels of 25-hydroxyvitamin D₃.³ Low levels of 25-hydroxyvitamin D₃ lead to alterations in cellular control over growth, differentiation, and function.

The active form of vitamin D is transported protein-bound in the blood to various target organs, where it is delivered in free form to cells. Specific nuclear receptor proteins are found in many organs not classically considered target organs for vitamin D, including the skin, brain, skeletal muscles, cardiomyocytes, vascular endothelial cells, circulating monocytes, and activated B and T lymphocytes. Vitamin D plays a significant role in the autocrine and paracrine regulation of cellular function, growth, and differentiation in various organs.³

MOST HEART FAILURE PATIENTS HAVE LOW VITAMIN D LEVELS

More than 40% of men and 50% of women in the United States have low vitamin D levels (< 30 ng/mL [75 nmol/L])—and low levels in adults are associated with both coronary artery disease and heart failure.⁴ Most patients with heart failure have low levels.^5,6 Therefore, screening for vitamin D deficiency in patients with heart failure is appropriate and encouraged.

Low vitamin D levels carry a poor prognosis. Pilz et al⁵ measured baseline 25-hydroxyvitamin D₃ levels in 3,299 patients referred for elective coronary angiography and followed them prospectively for a median of 7.7 years. Even after adjustment for cardiac risk factors, patients who had low 25-hydroxyvitamin D₃ levels were more likely to die of heart failure or sudden cardiac death than patients with normal levels.

Boxer et al⁷ found an association between low 25-hydroxyvitamin D₃ levels and low exercise capacity and frailty in patients with systolic heart failure.

LOW VITAMIN D CONTRIBUTES TO THE PATHOGENESIS OF HEART FAILURE

In recent years, ideas about the pathophysiology of heart failure have expanded from a purely hemodynamic view to a more complex concept involving inflammatory cytokines and neurohormonal overactivation.⁸

Animal studies first showed vitamin D to inhibit the renin-angiotensin-aldosterone system, activation of which contributes to the salt and water retention seen in heart failure.^4,9

In addition, vitamin D has a number of effects that should help prevent hypertension, an important risk factor for heart failure. It protects the kidney by suppressing the reninangiotensin-aldosterone system, prevents secondary hyperparathyroidism and its effects on vascular stiffness, prevents insulin resistance, and suppresses inflammation, which protects vascular endothelial cells.¹⁰

The first studies to show a connection between cardiovascular homeostasis and vitamin D status were in animal models more than 20 years ago. These studies showed that 1,25-dihydroxyvitamin D₃ acts directly on cardiomyocyte vitamin D receptors, which are widely distributed throughout the body in several tissue types.¹¹

Excess PTH levels associated with low vitamin D levels may play a role in cardiovascular disease by leading to cardiomyocyte hypertrophy and interstitial fibrosis of the heart.¹² Animal studies have found that vitamin D suppresses cardiac hypertrophy.¹³ Vitamin D also plays a role in cardiomyocyte relaxation and may abrogate the hypercontractility associated with diastolic heart failure.^2,14

Currently, it is unclear whether vitamin D deficiency is a causative risk factor for heart failure or simply a reflection of the poor functional status of patients with heart failure that leads to decreased exposure to sunlight. This debate will continue until further randomized clinical trials address this association.

VITAMIN D AND HEART TRANSPLANTATION

One would expect that patients with endstage organ failure would be at high risk of vitamin D deficiency because of limited sunlight exposure. However, few studies have evaluated the role of this vitamin in heart transplant recipients.

Stein and colleagues¹⁵ measured serum 25-hydroxyvitamin D₃ immediately after transplantation in 46 heart and 23 liver transplant recipients. Levels were low in both types of transplant recipients, but liver transplant recipients had significantly lower levels than heart transplant patients. This could be explained by malabsorption and impaired synthesis of 25-hydroxyvitamin D₃ in end-stage liver disease.

Also, an important point is that osteoporosis is prevalent in postcardiac transplant patients and likely related to the immunosuppressive agents these patients must take.¹⁶ In theory, increasing the body’s stores of vitamin D during the pretransplant period could lower the rate of bone loss and osteoporosis after cardiac transplantation.

Further investigation is needed to determine whether restoring adequate levels of vitamin D at the time of or after transplantation prevents graft rejection or improves survival.

VITAMIN D SUPPLEMENTATION AND SURVIVAL IN HEART FAILURE

The best laboratory test to assess vitamin D levels is the serum 25-hydroxyvitamin D₃ concentration. A level between 20 and 30 ng/mL (50–75 nmol/L) is considered insufficient, and a level below 20 ng/mL (50 nmol/L) represents vitamin D deficiency.^4,5,11

Vitamin D insufficiency is typically treated with 800 to 1,000 IU of vitamin D₃ daily, whereas deficiency requires 50,000 IU of vitamin D₃ weekly for 6 to 8 weeks, followed by 800 to 1,000 IU daily.¹⁹ The goal of therapy is to increase the serum 25-hydroxyvitamin D₃ level above 30 ng/mL.¹⁹

Currently, it is unknown if vitamin D supplementation improves survival in heart failure. We recommend testing for vitamin D deficiency in all patients with heart failure and treating them as described above. For heart failure patients that are not deficient, daily intake of 800 to 1,000 IU of vitamin D is reasonable. Our review underscores the need for more studies to evaluate the efficacy of vitamin D replacement in improving survival in patients with heart failure.

KEY POINTS

• Screening for vitamin D deficiency in patients with heart failure is appropriate and encouraged.
• Vitamin D deficiency is common in patients with heart failure and in heart transplant recipients.
• In theory, achieving adequate levels of vitamin D would have a beneficial effect on patients with heart failure.
• Randomized controlled trials are needed to determine if vitamin D supplementation confers a survival benefit in patients with heart failure who have deficient vitamin D levels.