A report that associates lower ICU mortality rates with multidisciplinary team rounding has one thought leader envisioning hospitalists as a key part of future collaborations.

The Feb. 22 study, "The Effect of Multidisciplinary Care Teams on Intensive Care Unit Mortality," included 107,324 patients at 112 hospitals (Arch Intern Med. 2010;170(4):369-376). Overall 30-day mortality was 18.3%. After making adjustments for patient and hospital characteristics, the team reported that multidisciplinary care was associated with significant reductions in the odds of death (odds ratio [OR], 0.84%; 95% confidence interval [CI], 0.76-0.93 [P=0.01]).

J. Perren Cobb, MD, of Massachusetts General Hospital in Boston wrote an accompanying editorial calling for physicians to see quality improvement (QI) projects tied to collaborative care as stepping stones to what he calls "health engineering." He defines the term as the "application of systems science to study how staff, patient, data, and equipment interactions can be engineered to optimize patient outcomes."

Dr. Cobb explains, for example, that hospitalists and intensivists can provide 24/7 care. "Hospitalists can bridge the care of the patient from the ICU to the non-ICU setting," he says.

Dr. Cobb wants competing factions in hospitals to share a "common vision" that studies patient care from both macro and micro perspectives. That encompasses everything from patient handoffs that require brief conversations between shifts to streamlining electronic medical records. His editorial focuses on the potential improvements in ICUs, but he notes that the "engineering of healthcare" can improve efficiency and efficacy across the continuum of care.

"The components are all there; they’ve been there for a long time," Dr. Cobb adds. "But what we're seeing in medicine is we’re evolving from 'seeing one patient at a time' to managing systems."

A report that associates lower ICU mortality rates with multidisciplinary team rounding has one thought leader envisioning hospitalists as a key part of future collaborations.

The Feb. 22 study, "The Effect of Multidisciplinary Care Teams on Intensive Care Unit Mortality," included 107,324 patients at 112 hospitals (Arch Intern Med. 2010;170(4):369-376). Overall 30-day mortality was 18.3%. After making adjustments for patient and hospital characteristics, the team reported that multidisciplinary care was associated with significant reductions in the odds of death (odds ratio [OR], 0.84%; 95% confidence interval [CI], 0.76-0.93 [P=0.01]).

J. Perren Cobb, MD, of Massachusetts General Hospital in Boston wrote an accompanying editorial calling for physicians to see quality improvement (QI) projects tied to collaborative care as stepping stones to what he calls "health engineering." He defines the term as the "application of systems science to study how staff, patient, data, and equipment interactions can be engineered to optimize patient outcomes."

Dr. Cobb explains, for example, that hospitalists and intensivists can provide 24/7 care. "Hospitalists can bridge the care of the patient from the ICU to the non-ICU setting," he says.

Dr. Cobb wants competing factions in hospitals to share a "common vision" that studies patient care from both macro and micro perspectives. That encompasses everything from patient handoffs that require brief conversations between shifts to streamlining electronic medical records. His editorial focuses on the potential improvements in ICUs, but he notes that the "engineering of healthcare" can improve efficiency and efficacy across the continuum of care.

"The components are all there; they’ve been there for a long time," Dr. Cobb adds. "But what we're seeing in medicine is we’re evolving from 'seeing one patient at a time' to managing systems."

A report that associates lower ICU mortality rates with multidisciplinary team rounding has one thought leader envisioning hospitalists as a key part of future collaborations.

The Feb. 22 study, "The Effect of Multidisciplinary Care Teams on Intensive Care Unit Mortality," included 107,324 patients at 112 hospitals (Arch Intern Med. 2010;170(4):369-376). Overall 30-day mortality was 18.3%. After making adjustments for patient and hospital characteristics, the team reported that multidisciplinary care was associated with significant reductions in the odds of death (odds ratio [OR], 0.84%; 95% confidence interval [CI], 0.76-0.93 [P=0.01]).

J. Perren Cobb, MD, of Massachusetts General Hospital in Boston wrote an accompanying editorial calling for physicians to see quality improvement (QI) projects tied to collaborative care as stepping stones to what he calls "health engineering." He defines the term as the "application of systems science to study how staff, patient, data, and equipment interactions can be engineered to optimize patient outcomes."

Dr. Cobb explains, for example, that hospitalists and intensivists can provide 24/7 care. "Hospitalists can bridge the care of the patient from the ICU to the non-ICU setting," he says.

Dr. Cobb wants competing factions in hospitals to share a "common vision" that studies patient care from both macro and micro perspectives. That encompasses everything from patient handoffs that require brief conversations between shifts to streamlining electronic medical records. His editorial focuses on the potential improvements in ICUs, but he notes that the "engineering of healthcare" can improve efficiency and efficacy across the continuum of care.

"The components are all there; they’ve been there for a long time," Dr. Cobb adds. "But what we're seeing in medicine is we’re evolving from 'seeing one patient at a time' to managing systems."

With hospitalist demand outstripping supply, a fine-tuned group schedule can enhance productivity and job satisfaction. Two HM group leaders recently spoke with TH eWire about how they avoid a one-size-fits-all approach.

Stephen Houff, MD, president and CEO of Canton, Ohio-based Hospitalists Management Group, deploys 350 hospitalists to 41 hospitals in 11 states. Groups average eight hospitalists (range four to 20), and have an average daily census (ADC) of 50. Most work a seven-on/seven-off block shift. Dr. Houff says his HM groups create effective schedules in the following ways:

• In an eight-person group, three hospitalists work 7 a.m. to 7 p.m., and one doctor staffs the ED from 11 a.m. to 11 p.m.;
• Members must work four consecutive days;
• After getting established in a location, HM groups find local office-based PCPs to moonlight, covering their malpractice insurance and billing; and
• A dozen HMG hospitalists known as “firefighters” cover emergency or planned short-term leaves, receiving 15% higher pay plus per diems. 

Haiwen Ma, MD, PhD, director of Hospitalist Services at South Nassau Communities Hospital in Oceanside, N.Y., has two nocturnists and five hospitalists in the group who work Monday through Friday from 7 a.m. to 7 p.m. The group has an ADC of 45-50 and a 15-patient cap per hospitalist. Here’s how she makes it work:

• Four hospitalists cover admissions in three-hour blocks from 7 a.m. to 7 p.m. and do weekend calls every fourth week; 
• The fifth hospitalist performs pre-surgical/post-surgical consults; and
• The group relies on per-diem moonlighters from other hospitals to pick up the slack.

For more scheduling tips, check out practice management articles on our Web site.

With hospitalist demand outstripping supply, a fine-tuned group schedule can enhance productivity and job satisfaction. Two HM group leaders recently spoke with TH eWire about how they avoid a one-size-fits-all approach.

Stephen Houff, MD, president and CEO of Canton, Ohio-based Hospitalists Management Group, deploys 350 hospitalists to 41 hospitals in 11 states. Groups average eight hospitalists (range four to 20), and have an average daily census (ADC) of 50. Most work a seven-on/seven-off block shift. Dr. Houff says his HM groups create effective schedules in the following ways:

• In an eight-person group, three hospitalists work 7 a.m. to 7 p.m., and one doctor staffs the ED from 11 a.m. to 11 p.m.;
• Members must work four consecutive days;
• After getting established in a location, HM groups find local office-based PCPs to moonlight, covering their malpractice insurance and billing; and
• A dozen HMG hospitalists known as “firefighters” cover emergency or planned short-term leaves, receiving 15% higher pay plus per diems. 

Haiwen Ma, MD, PhD, director of Hospitalist Services at South Nassau Communities Hospital in Oceanside, N.Y., has two nocturnists and five hospitalists in the group who work Monday through Friday from 7 a.m. to 7 p.m. The group has an ADC of 45-50 and a 15-patient cap per hospitalist. Here’s how she makes it work:

• Four hospitalists cover admissions in three-hour blocks from 7 a.m. to 7 p.m. and do weekend calls every fourth week; 
• The fifth hospitalist performs pre-surgical/post-surgical consults; and
• The group relies on per-diem moonlighters from other hospitals to pick up the slack.

For more scheduling tips, check out practice management articles on our Web site.

With hospitalist demand outstripping supply, a fine-tuned group schedule can enhance productivity and job satisfaction. Two HM group leaders recently spoke with TH eWire about how they avoid a one-size-fits-all approach.

Stephen Houff, MD, president and CEO of Canton, Ohio-based Hospitalists Management Group, deploys 350 hospitalists to 41 hospitals in 11 states. Groups average eight hospitalists (range four to 20), and have an average daily census (ADC) of 50. Most work a seven-on/seven-off block shift. Dr. Houff says his HM groups create effective schedules in the following ways:

• In an eight-person group, three hospitalists work 7 a.m. to 7 p.m., and one doctor staffs the ED from 11 a.m. to 11 p.m.;
• Members must work four consecutive days;
• After getting established in a location, HM groups find local office-based PCPs to moonlight, covering their malpractice insurance and billing; and
• A dozen HMG hospitalists known as “firefighters” cover emergency or planned short-term leaves, receiving 15% higher pay plus per diems. 

Haiwen Ma, MD, PhD, director of Hospitalist Services at South Nassau Communities Hospital in Oceanside, N.Y., has two nocturnists and five hospitalists in the group who work Monday through Friday from 7 a.m. to 7 p.m. The group has an ADC of 45-50 and a 15-patient cap per hospitalist. Here’s how she makes it work:

• Four hospitalists cover admissions in three-hour blocks from 7 a.m. to 7 p.m. and do weekend calls every fourth week; 
• The fifth hospitalist performs pre-surgical/post-surgical consults; and
• The group relies on per-diem moonlighters from other hospitals to pick up the slack.

For more scheduling tips, check out practice management articles on our Web site.

Editor’s note: Third of a three-part series.

In the two monthly columns preceding this one, I’ve provided an overview of some ways hospitalist groups distribute new referrals among the providers. This month, I’ll review things that cause some groups to make exceptions to their typical method of distributing patients, and turn from how patients are distributed over 24 hours to thoughts about how they might be assigned over the course of consecutive days worked by a doctor.

Equitable Exceptions

There are a number of reasons groups decide to depart from their typical method of assigning patients. These include:

• “Bouncebacks”;
• One hospitalist is at the cap, others aren’t;
• Consult requested of a specific hospitalist;
• Hospitalists with unique skills (e.g., ICU expertise); and
• A patient “fires” the hospitalist.

There isn’t a standard “hospitalist way” of dealing with these issues, and each group will need to work out its own system. The most common of these issues is “bouncebacks.” Every group should try to have patients readmitted within three or four days of discharge go back to the discharging hospitalist. However, this proves difficult in many cases for several reasons, most commonly because the original discharging doctor might not be working when the patient returns.

The Alpha & Omega

Nearly every hospitalist practice makes some effort to maximize continuity between a single hospitalist and patient over the course of a hospital stay. But the effect of the method of patient assignment on continuity often is overlooked.

A reasonable way to think about or measure continuity is to estimate the portion of patients seen by the group that see the same hospitalist for each daytime visit over the course of their stay. (Assume that in most HM groups the same hospitalist can’t make both day and night visits over the course of the hospital stay. So, just for simplicity, I’ve intentionally left night visits, including an initial admission visit at night, out of the continuity calculation.) Plug the numbers for your practice into the formula (see Figure 1, right) and see what you get.

If a hospitalist always works seven consecutive day shifts (e.g., a seven-on/seven-off schedule) and the hospitalist’s patients have an average LOS of 4.2 days, then 54% of patients will see the same hospitalist for all daytime visits, and 46% will experience at least one handoff. (To keep things simple, I’m ignoring the effect on continuity of patients being admitted by an “admitter” or nocturnist who doesn’t see the patient subsequently.)

Changing the number of consecutive day shifts a hospitalist works has the most significant impact on continuity, but just how many consecutive days can one work routinely before fatigue and burnout—not too mention increased errors and decreased patient satisfaction—become a problem? (Many hospitalists make the mistake of trying to stuff what might be a reasonable annual workload into the smallest number of shifts possible with the goal of maximizing the number of days off. That means each worked day will be very busy, making it really hard to work many consecutive days. But you always have the option of titrating out that same annual workload over more days so that each day is less busy and it becomes easier to work more consecutive days.)

An often-overlooked way to improve continuity without having to work more consecutive day shifts is to have a hospitalist who is early in their series of worked days take on more new admissions and consults, and perhaps exempt that doctor from taking on new referrals for the last day or two he or she is on service. Eric Howell, MD, FHM, an SHM board member, calls this method “slam and dwindle.” This has been the approach I’ve experienced my whole career, and it is hard for me to imagine doing it any other way.

Here’s how it might work: Let’s say Dr. Petty always works seven consecutive day shifts, and on the first day he picks up a list of patients remaining from the doctor he’s replacing. To keep things simple, let’s assume he’s not in a large group, and during his first day of seven days on service he accepts and “keeps” all new referrals to the practice. On each successive day, he might assume the care of some new patients, but none on days six and seven. This means he takes on a disproportionately large number of new referrals at the beginning of his consecutive worked days, or “front-loads” new referrals. And because many of these patients will discharge before the end of his seven days and he takes on no new patients on days six and seven, his census will drop a lot before he rotates off, which in turn means there will be few patients who will have to get to know a new doctor on the first day Dr. Petty starts his seven-off schedule.

This system of patient distribution means continuity improved without requiring Dr. Petty to work more consecutive day shifts. Even though he works seven consecutive days and his average (or median) LOS is 4.2, as in the example above, his continuity will be much better than 54%. In fact, as many as 70% to 80% of Dr. Petty’s patients will see him for every daytime visit during their stay.

click for large version

Other benefits of assigning more patients early and none late in a series of worked days are that on his last day of service, he will have more time to “tee up” patients for the next doctor, including preparing for patients anticipated to discharge the next day (e.g., dictate discharge summary, complete paperwork, etc.), and might be able to wrap up a little earlier that day. And when rotating back on service, he will pick up a small list of patients left by Dr. Tench, maybe fewer than eight, rather than the group’s average daily load of 15 patients per doctor, so he will have the capacity to admit a lot of patients that day.

I think there are three main reasons this isn’t a more common approach:

1. Many HM groups just haven’t considered it.
2. HM groups might have a schedule that has all doctors rotate off/on the same days each week. For example, all doctors rotate off on Tuesdays and are replaced by new doctors on Wednesday. That makes it impossible to exempt a doctor from taking on new referrals on the last day of service because all of the group’s doctors have their last day on Tuesday. These groups could stagger the day each doctor rotates off—one on Monday, one on Tuesday, and so on.
3. Every doctor is so busy each day that it wouldn’t be feasible to exempt any individual doctor from taking on new patients, even if they are off the next day.

Despite the difficulties implementing a system of front-loading new referrals, I think most hospitalists would find that they like it. Because it reduces handoffs, it reduces, at least modestly, the group’s overall workload and probably benefits the group’s quality and patient satisfaction. TH

Dr. Nelson has been a practicing hospitalist since 1988 and is co-founder and past president of SHM. He is a principal in Nelson Flores Hospital Medicine Consultants, a national hospitalist practice management consulting firm (www.nelsonflores.com). He is also course co-director and faculty for SHM’s “Best Practices in Managing a Hospital Medicine Program” course. This column represents his views and is not intended to reflect an official position of SHM.

Editor’s note: Third of a three-part series.

In the two monthly columns preceding this one, I’ve provided an overview of some ways hospitalist groups distribute new referrals among the providers. This month, I’ll review things that cause some groups to make exceptions to their typical method of distributing patients, and turn from how patients are distributed over 24 hours to thoughts about how they might be assigned over the course of consecutive days worked by a doctor.

Equitable Exceptions

There are a number of reasons groups decide to depart from their typical method of assigning patients. These include:

• “Bouncebacks”;
• One hospitalist is at the cap, others aren’t;
• Consult requested of a specific hospitalist;
• Hospitalists with unique skills (e.g., ICU expertise); and
• A patient “fires” the hospitalist.

There isn’t a standard “hospitalist way” of dealing with these issues, and each group will need to work out its own system. The most common of these issues is “bouncebacks.” Every group should try to have patients readmitted within three or four days of discharge go back to the discharging hospitalist. However, this proves difficult in many cases for several reasons, most commonly because the original discharging doctor might not be working when the patient returns.

The Alpha & Omega

Nearly every hospitalist practice makes some effort to maximize continuity between a single hospitalist and patient over the course of a hospital stay. But the effect of the method of patient assignment on continuity often is overlooked.

A reasonable way to think about or measure continuity is to estimate the portion of patients seen by the group that see the same hospitalist for each daytime visit over the course of their stay. (Assume that in most HM groups the same hospitalist can’t make both day and night visits over the course of the hospital stay. So, just for simplicity, I’ve intentionally left night visits, including an initial admission visit at night, out of the continuity calculation.) Plug the numbers for your practice into the formula (see Figure 1, right) and see what you get.

If a hospitalist always works seven consecutive day shifts (e.g., a seven-on/seven-off schedule) and the hospitalist’s patients have an average LOS of 4.2 days, then 54% of patients will see the same hospitalist for all daytime visits, and 46% will experience at least one handoff. (To keep things simple, I’m ignoring the effect on continuity of patients being admitted by an “admitter” or nocturnist who doesn’t see the patient subsequently.)

Changing the number of consecutive day shifts a hospitalist works has the most significant impact on continuity, but just how many consecutive days can one work routinely before fatigue and burnout—not too mention increased errors and decreased patient satisfaction—become a problem? (Many hospitalists make the mistake of trying to stuff what might be a reasonable annual workload into the smallest number of shifts possible with the goal of maximizing the number of days off. That means each worked day will be very busy, making it really hard to work many consecutive days. But you always have the option of titrating out that same annual workload over more days so that each day is less busy and it becomes easier to work more consecutive days.)

An often-overlooked way to improve continuity without having to work more consecutive day shifts is to have a hospitalist who is early in their series of worked days take on more new admissions and consults, and perhaps exempt that doctor from taking on new referrals for the last day or two he or she is on service. Eric Howell, MD, FHM, an SHM board member, calls this method “slam and dwindle.” This has been the approach I’ve experienced my whole career, and it is hard for me to imagine doing it any other way.

Here’s how it might work: Let’s say Dr. Petty always works seven consecutive day shifts, and on the first day he picks up a list of patients remaining from the doctor he’s replacing. To keep things simple, let’s assume he’s not in a large group, and during his first day of seven days on service he accepts and “keeps” all new referrals to the practice. On each successive day, he might assume the care of some new patients, but none on days six and seven. This means he takes on a disproportionately large number of new referrals at the beginning of his consecutive worked days, or “front-loads” new referrals. And because many of these patients will discharge before the end of his seven days and he takes on no new patients on days six and seven, his census will drop a lot before he rotates off, which in turn means there will be few patients who will have to get to know a new doctor on the first day Dr. Petty starts his seven-off schedule.

This system of patient distribution means continuity improved without requiring Dr. Petty to work more consecutive day shifts. Even though he works seven consecutive days and his average (or median) LOS is 4.2, as in the example above, his continuity will be much better than 54%. In fact, as many as 70% to 80% of Dr. Petty’s patients will see him for every daytime visit during their stay.

click for large version

Other benefits of assigning more patients early and none late in a series of worked days are that on his last day of service, he will have more time to “tee up” patients for the next doctor, including preparing for patients anticipated to discharge the next day (e.g., dictate discharge summary, complete paperwork, etc.), and might be able to wrap up a little earlier that day. And when rotating back on service, he will pick up a small list of patients left by Dr. Tench, maybe fewer than eight, rather than the group’s average daily load of 15 patients per doctor, so he will have the capacity to admit a lot of patients that day.

I think there are three main reasons this isn’t a more common approach:

1. Many HM groups just haven’t considered it.
2. HM groups might have a schedule that has all doctors rotate off/on the same days each week. For example, all doctors rotate off on Tuesdays and are replaced by new doctors on Wednesday. That makes it impossible to exempt a doctor from taking on new referrals on the last day of service because all of the group’s doctors have their last day on Tuesday. These groups could stagger the day each doctor rotates off—one on Monday, one on Tuesday, and so on.
3. Every doctor is so busy each day that it wouldn’t be feasible to exempt any individual doctor from taking on new patients, even if they are off the next day.

Despite the difficulties implementing a system of front-loading new referrals, I think most hospitalists would find that they like it. Because it reduces handoffs, it reduces, at least modestly, the group’s overall workload and probably benefits the group’s quality and patient satisfaction. TH

Dr. Nelson has been a practicing hospitalist since 1988 and is co-founder and past president of SHM. He is a principal in Nelson Flores Hospital Medicine Consultants, a national hospitalist practice management consulting firm (www.nelsonflores.com). He is also course co-director and faculty for SHM’s “Best Practices in Managing a Hospital Medicine Program” course. This column represents his views and is not intended to reflect an official position of SHM.

Editor’s note: Third of a three-part series.

In the two monthly columns preceding this one, I’ve provided an overview of some ways hospitalist groups distribute new referrals among the providers. This month, I’ll review things that cause some groups to make exceptions to their typical method of distributing patients, and turn from how patients are distributed over 24 hours to thoughts about how they might be assigned over the course of consecutive days worked by a doctor.

Equitable Exceptions

There are a number of reasons groups decide to depart from their typical method of assigning patients. These include:

• “Bouncebacks”;
• One hospitalist is at the cap, others aren’t;
• Consult requested of a specific hospitalist;
• Hospitalists with unique skills (e.g., ICU expertise); and
• A patient “fires” the hospitalist.

There isn’t a standard “hospitalist way” of dealing with these issues, and each group will need to work out its own system. The most common of these issues is “bouncebacks.” Every group should try to have patients readmitted within three or four days of discharge go back to the discharging hospitalist. However, this proves difficult in many cases for several reasons, most commonly because the original discharging doctor might not be working when the patient returns.

The Alpha & Omega

Nearly every hospitalist practice makes some effort to maximize continuity between a single hospitalist and patient over the course of a hospital stay. But the effect of the method of patient assignment on continuity often is overlooked.

A reasonable way to think about or measure continuity is to estimate the portion of patients seen by the group that see the same hospitalist for each daytime visit over the course of their stay. (Assume that in most HM groups the same hospitalist can’t make both day and night visits over the course of the hospital stay. So, just for simplicity, I’ve intentionally left night visits, including an initial admission visit at night, out of the continuity calculation.) Plug the numbers for your practice into the formula (see Figure 1, right) and see what you get.

If a hospitalist always works seven consecutive day shifts (e.g., a seven-on/seven-off schedule) and the hospitalist’s patients have an average LOS of 4.2 days, then 54% of patients will see the same hospitalist for all daytime visits, and 46% will experience at least one handoff. (To keep things simple, I’m ignoring the effect on continuity of patients being admitted by an “admitter” or nocturnist who doesn’t see the patient subsequently.)

Changing the number of consecutive day shifts a hospitalist works has the most significant impact on continuity, but just how many consecutive days can one work routinely before fatigue and burnout—not too mention increased errors and decreased patient satisfaction—become a problem? (Many hospitalists make the mistake of trying to stuff what might be a reasonable annual workload into the smallest number of shifts possible with the goal of maximizing the number of days off. That means each worked day will be very busy, making it really hard to work many consecutive days. But you always have the option of titrating out that same annual workload over more days so that each day is less busy and it becomes easier to work more consecutive days.)

An often-overlooked way to improve continuity without having to work more consecutive day shifts is to have a hospitalist who is early in their series of worked days take on more new admissions and consults, and perhaps exempt that doctor from taking on new referrals for the last day or two he or she is on service. Eric Howell, MD, FHM, an SHM board member, calls this method “slam and dwindle.” This has been the approach I’ve experienced my whole career, and it is hard for me to imagine doing it any other way.

Here’s how it might work: Let’s say Dr. Petty always works seven consecutive day shifts, and on the first day he picks up a list of patients remaining from the doctor he’s replacing. To keep things simple, let’s assume he’s not in a large group, and during his first day of seven days on service he accepts and “keeps” all new referrals to the practice. On each successive day, he might assume the care of some new patients, but none on days six and seven. This means he takes on a disproportionately large number of new referrals at the beginning of his consecutive worked days, or “front-loads” new referrals. And because many of these patients will discharge before the end of his seven days and he takes on no new patients on days six and seven, his census will drop a lot before he rotates off, which in turn means there will be few patients who will have to get to know a new doctor on the first day Dr. Petty starts his seven-off schedule.

This system of patient distribution means continuity improved without requiring Dr. Petty to work more consecutive day shifts. Even though he works seven consecutive days and his average (or median) LOS is 4.2, as in the example above, his continuity will be much better than 54%. In fact, as many as 70% to 80% of Dr. Petty’s patients will see him for every daytime visit during their stay.

click for large version

Other benefits of assigning more patients early and none late in a series of worked days are that on his last day of service, he will have more time to “tee up” patients for the next doctor, including preparing for patients anticipated to discharge the next day (e.g., dictate discharge summary, complete paperwork, etc.), and might be able to wrap up a little earlier that day. And when rotating back on service, he will pick up a small list of patients left by Dr. Tench, maybe fewer than eight, rather than the group’s average daily load of 15 patients per doctor, so he will have the capacity to admit a lot of patients that day.

I think there are three main reasons this isn’t a more common approach:

1. Many HM groups just haven’t considered it.
2. HM groups might have a schedule that has all doctors rotate off/on the same days each week. For example, all doctors rotate off on Tuesdays and are replaced by new doctors on Wednesday. That makes it impossible to exempt a doctor from taking on new referrals on the last day of service because all of the group’s doctors have their last day on Tuesday. These groups could stagger the day each doctor rotates off—one on Monday, one on Tuesday, and so on.
3. Every doctor is so busy each day that it wouldn’t be feasible to exempt any individual doctor from taking on new patients, even if they are off the next day.

Despite the difficulties implementing a system of front-loading new referrals, I think most hospitalists would find that they like it. Because it reduces handoffs, it reduces, at least modestly, the group’s overall workload and probably benefits the group’s quality and patient satisfaction. TH

Dr. Nelson has been a practicing hospitalist since 1988 and is co-founder and past president of SHM. He is a principal in Nelson Flores Hospital Medicine Consultants, a national hospitalist practice management consulting firm (www.nelsonflores.com). He is also course co-director and faculty for SHM’s “Best Practices in Managing a Hospital Medicine Program” course. This column represents his views and is not intended to reflect an official position of SHM.

Silence.

Alone, I’m surrounded by strobes of memories—the baby monitor wresting us from sleep … muffled choking sounds … my wife holding our pale, stridorous 2-year-old … desperate attempts to clear his airway … the studied detachment of the 911 operator … paramedics … my wife running from the house without a jacket ... the fading ululations of the ambulance … silence.

I’m left in the bathroom, heart jack-hammering, holding a bloodied towel. Just 20 minutes earlier, I was cloaked in deep sleep. Now I’m shrouded with dread and cold sweat, my wife and son gone—leaving me to tend to our sleeping three-month-old daughter. The night ultimately ends well—perhaps comically, even—but not before being defined by three common cognitive errors.

History of Present Illness

It was a Monday night, and, after putting our kids down, my wife and I retired early to get a good night’s rest. An hour later, we awoke to gasping sounds from the monitor. My son, Grey, who was fine before bedtime, was panting and wheezing, unable to secure a full breath.

I immediately recalled that the night prior he had gagged on a dissolvable “gummy bear” vitamin. As he projected the appearance of someone who had aspirated something, we commenced manual sweeps of his mouth—feeling something in its deepest recesses. Gummy bear? Uvula? After numerous retching attempts to dislodge it, we moved on to Heimlich maneuvers. Nothing.

Just then, the paramedics showed up and took over, hearing this history of present illness.

Momentum Shift

An hour later, having secured a sitter for our sleeping infant, I showed up at the ED. Interestingly, the gummy-bear premise, nothing more than a harried utterance, had gathered the momentum of a boulder rolling downhill. The paramedics had relayed the possibility that our son might have aspirated a vitamin to the ED doctor, who relayed this certainty to the ear, nose, and throat doctor, who was actively scheduling operating-room time to bronchoscopically remove the offending foreign body.

It was all a bit like that childhood game of Telephone, in which the original message gets incrementally distorted with each telling, such that what starts as “Johnny told me he likes Lisa” turns into “Johnny crushed Lisa.”

My inner physician, elbowing the nervous parent aside, asked about the evidence for an aspiration. “The X-ray was negative, as was the exam, but the history suggests aspiration,” the ENT told me.

“What history?” I asked.

“That he has a history of ‘tonguing’ vitamins,” he said.

“Tonguing vitamins?” I responded, incredulously feeling the need to defend my child’s pill-swallowing honor. “Where did that story come from? We aren’t even sure we gave him a vitamin tonight.”

Nonetheless, the ENT was confident that “kids aspirate things all the time.”

Skeptical, I continued the debate. “But what if we hadn’t given that history? Would you still think of aspiration in this case?”

“Probably not, but then you did give us that history,” he replied. “So we need to bronch him.”

Culprit Revealed

Meanwhile, Grey was looking better with supplemental oxygen and a nebulizer’s worth of racemic epinephrine. His stridor took on more of a “barking seal” nature, and 30 minutes later, he developed a fever characteristic of croup. After a dose of steroids and another whiff of racemic epi, he was himself again, laughing the laugh of a wounded seal at the pulse oximeter, which backlit his big toe red. Comedy-club-level laughter replaced the look of death in the matter of an hour, as I was reminded of the resiliency of children. If only Mom and Dad could capture a bit of that.

Feeling a cocktail of relief and embarrassment—how could two physicians misdiagnose croup as an aspirated foreign body?—we readied ourselves for discharge. Just then, the ENT doctor came back in and told us the OR would be ready in a few hours. “But,” I inquired, “isn’t this just croup?”

“Most likely,” he replied, “but we can’t rule out aspiration without a bronchoscopy.”

It was then that I realized we (and our medical team) had fallen victim to some common heuristical errors. Heuristics are those little shortcuts in logic that we utilize to solve common problems. They are bred from years of experience and helpfully get us home every night in time for dinner. Without them, medicine would be a painstaking, Everlasting Gobstopper-like journey through endless differential diagnoses—in other words, your four-hour clerkship patient evaluations in medical school.

These shortcuts allow us to quickly recognize that a diaphoretic, 60-year-old man with diabetes, hyperlipidemia, and substernal chest pain has an acute coronary syndrome. We don’t spend hours thinking of Tietze’s syndrome, Boerhaave’s disease, and their ilk, because our mind quickly takes the shortcut to the right diagnosis. Although helpful, these shortcuts can cut both ways, occasionally resulting in thrombolytic therapy for an aortic dissection.

This is where Grey’s situation went wrong. My wife and I were victimized by the availability bias. This cognitive bias occurs when a recently encountered situation is given undue stature solely because of its proximity in time to the next event—i.e., it is “available.” So, because my son choked on a vitamin the night before, he must be choking on a vitamin the next night. (Even though we didn’t give him a vitamin and hours had passed since we put him to bed.) There is little connection between the two events, outside of the fact that aspiration is at the fore of your mind. This happens to us all the time. Think about the last presentation you attended about an obscure topic, only to amazingly find that the very next day, you had not one but two patients who surely required a workup for acute intermittent porphyria.

Common Practices

Anchoring bias is another common cognitive error in which we overly rely on one piece of information, the “anchor.” This was certainly in play during our ED visit. The mere mention of an aspirated foreign body was latched on to immediately. From there, tidbits of information that supported that diagnosis (something in the back of his throat on our exam, kids aspirate all the time) were kept, while the unsupporting evidence (negative X-ray and exam findings, fever, barking cough that awakes a kid at night) was jettisoned.

We fell prey to the momentum bias. This heuristical hiccup frequently wreaks cross-coverage havoc. You’ve seen this, I’m sure. Because the day team thought the renal failure was due to prerenal azotemia, the night team harmonizes, continuing to treat the patient’s bladder outlet obstruction with volume challenges. That is until someone—in my sphere, it’s usually the third-year medical student—asks if this could all be from the patient’s benign prostatic hyperplasia and medications.

After convincing our well-intentioned ENT colleague to call off the bronch, I was left with the important lesson that the ways in which our minds work, also well-intentioned, can cause us fits of trouble. I was left with the realization that the only way to mitigate the risk these cognitive shortcuts pose is to be constantly vigilant of their presence.

And, perhaps most importantly, I was left with an overstimulated 2-year-old high on the excitement of a hospital visit and large doses of adrenaline—a combination that left me desperately yearning for silence. TH

Dr. Glasheen is The Hospitalist’s physician editor.

Silence.

Alone, I’m surrounded by strobes of memories—the baby monitor wresting us from sleep … muffled choking sounds … my wife holding our pale, stridorous 2-year-old … desperate attempts to clear his airway … the studied detachment of the 911 operator … paramedics … my wife running from the house without a jacket ... the fading ululations of the ambulance … silence.

I’m left in the bathroom, heart jack-hammering, holding a bloodied towel. Just 20 minutes earlier, I was cloaked in deep sleep. Now I’m shrouded with dread and cold sweat, my wife and son gone—leaving me to tend to our sleeping three-month-old daughter. The night ultimately ends well—perhaps comically, even—but not before being defined by three common cognitive errors.

History of Present Illness

It was a Monday night, and, after putting our kids down, my wife and I retired early to get a good night’s rest. An hour later, we awoke to gasping sounds from the monitor. My son, Grey, who was fine before bedtime, was panting and wheezing, unable to secure a full breath.

I immediately recalled that the night prior he had gagged on a dissolvable “gummy bear” vitamin. As he projected the appearance of someone who had aspirated something, we commenced manual sweeps of his mouth—feeling something in its deepest recesses. Gummy bear? Uvula? After numerous retching attempts to dislodge it, we moved on to Heimlich maneuvers. Nothing.

Just then, the paramedics showed up and took over, hearing this history of present illness.

Momentum Shift

An hour later, having secured a sitter for our sleeping infant, I showed up at the ED. Interestingly, the gummy-bear premise, nothing more than a harried utterance, had gathered the momentum of a boulder rolling downhill. The paramedics had relayed the possibility that our son might have aspirated a vitamin to the ED doctor, who relayed this certainty to the ear, nose, and throat doctor, who was actively scheduling operating-room time to bronchoscopically remove the offending foreign body.

It was all a bit like that childhood game of Telephone, in which the original message gets incrementally distorted with each telling, such that what starts as “Johnny told me he likes Lisa” turns into “Johnny crushed Lisa.”

My inner physician, elbowing the nervous parent aside, asked about the evidence for an aspiration. “The X-ray was negative, as was the exam, but the history suggests aspiration,” the ENT told me.

“What history?” I asked.

“That he has a history of ‘tonguing’ vitamins,” he said.

“Tonguing vitamins?” I responded, incredulously feeling the need to defend my child’s pill-swallowing honor. “Where did that story come from? We aren’t even sure we gave him a vitamin tonight.”

Nonetheless, the ENT was confident that “kids aspirate things all the time.”

Skeptical, I continued the debate. “But what if we hadn’t given that history? Would you still think of aspiration in this case?”

“Probably not, but then you did give us that history,” he replied. “So we need to bronch him.”

Culprit Revealed

Meanwhile, Grey was looking better with supplemental oxygen and a nebulizer’s worth of racemic epinephrine. His stridor took on more of a “barking seal” nature, and 30 minutes later, he developed a fever characteristic of croup. After a dose of steroids and another whiff of racemic epi, he was himself again, laughing the laugh of a wounded seal at the pulse oximeter, which backlit his big toe red. Comedy-club-level laughter replaced the look of death in the matter of an hour, as I was reminded of the resiliency of children. If only Mom and Dad could capture a bit of that.

Feeling a cocktail of relief and embarrassment—how could two physicians misdiagnose croup as an aspirated foreign body?—we readied ourselves for discharge. Just then, the ENT doctor came back in and told us the OR would be ready in a few hours. “But,” I inquired, “isn’t this just croup?”

“Most likely,” he replied, “but we can’t rule out aspiration without a bronchoscopy.”

It was then that I realized we (and our medical team) had fallen victim to some common heuristical errors. Heuristics are those little shortcuts in logic that we utilize to solve common problems. They are bred from years of experience and helpfully get us home every night in time for dinner. Without them, medicine would be a painstaking, Everlasting Gobstopper-like journey through endless differential diagnoses—in other words, your four-hour clerkship patient evaluations in medical school.

These shortcuts allow us to quickly recognize that a diaphoretic, 60-year-old man with diabetes, hyperlipidemia, and substernal chest pain has an acute coronary syndrome. We don’t spend hours thinking of Tietze’s syndrome, Boerhaave’s disease, and their ilk, because our mind quickly takes the shortcut to the right diagnosis. Although helpful, these shortcuts can cut both ways, occasionally resulting in thrombolytic therapy for an aortic dissection.

This is where Grey’s situation went wrong. My wife and I were victimized by the availability bias. This cognitive bias occurs when a recently encountered situation is given undue stature solely because of its proximity in time to the next event—i.e., it is “available.” So, because my son choked on a vitamin the night before, he must be choking on a vitamin the next night. (Even though we didn’t give him a vitamin and hours had passed since we put him to bed.) There is little connection between the two events, outside of the fact that aspiration is at the fore of your mind. This happens to us all the time. Think about the last presentation you attended about an obscure topic, only to amazingly find that the very next day, you had not one but two patients who surely required a workup for acute intermittent porphyria.

Common Practices

Anchoring bias is another common cognitive error in which we overly rely on one piece of information, the “anchor.” This was certainly in play during our ED visit. The mere mention of an aspirated foreign body was latched on to immediately. From there, tidbits of information that supported that diagnosis (something in the back of his throat on our exam, kids aspirate all the time) were kept, while the unsupporting evidence (negative X-ray and exam findings, fever, barking cough that awakes a kid at night) was jettisoned.

We fell prey to the momentum bias. This heuristical hiccup frequently wreaks cross-coverage havoc. You’ve seen this, I’m sure. Because the day team thought the renal failure was due to prerenal azotemia, the night team harmonizes, continuing to treat the patient’s bladder outlet obstruction with volume challenges. That is until someone—in my sphere, it’s usually the third-year medical student—asks if this could all be from the patient’s benign prostatic hyperplasia and medications.

After convincing our well-intentioned ENT colleague to call off the bronch, I was left with the important lesson that the ways in which our minds work, also well-intentioned, can cause us fits of trouble. I was left with the realization that the only way to mitigate the risk these cognitive shortcuts pose is to be constantly vigilant of their presence.

And, perhaps most importantly, I was left with an overstimulated 2-year-old high on the excitement of a hospital visit and large doses of adrenaline—a combination that left me desperately yearning for silence. TH

Dr. Glasheen is The Hospitalist’s physician editor.

Silence.

Alone, I’m surrounded by strobes of memories—the baby monitor wresting us from sleep … muffled choking sounds … my wife holding our pale, stridorous 2-year-old … desperate attempts to clear his airway … the studied detachment of the 911 operator … paramedics … my wife running from the house without a jacket ... the fading ululations of the ambulance … silence.

I’m left in the bathroom, heart jack-hammering, holding a bloodied towel. Just 20 minutes earlier, I was cloaked in deep sleep. Now I’m shrouded with dread and cold sweat, my wife and son gone—leaving me to tend to our sleeping three-month-old daughter. The night ultimately ends well—perhaps comically, even—but not before being defined by three common cognitive errors.

History of Present Illness

It was a Monday night, and, after putting our kids down, my wife and I retired early to get a good night’s rest. An hour later, we awoke to gasping sounds from the monitor. My son, Grey, who was fine before bedtime, was panting and wheezing, unable to secure a full breath.

I immediately recalled that the night prior he had gagged on a dissolvable “gummy bear” vitamin. As he projected the appearance of someone who had aspirated something, we commenced manual sweeps of his mouth—feeling something in its deepest recesses. Gummy bear? Uvula? After numerous retching attempts to dislodge it, we moved on to Heimlich maneuvers. Nothing.

Just then, the paramedics showed up and took over, hearing this history of present illness.

Momentum Shift

An hour later, having secured a sitter for our sleeping infant, I showed up at the ED. Interestingly, the gummy-bear premise, nothing more than a harried utterance, had gathered the momentum of a boulder rolling downhill. The paramedics had relayed the possibility that our son might have aspirated a vitamin to the ED doctor, who relayed this certainty to the ear, nose, and throat doctor, who was actively scheduling operating-room time to bronchoscopically remove the offending foreign body.

It was all a bit like that childhood game of Telephone, in which the original message gets incrementally distorted with each telling, such that what starts as “Johnny told me he likes Lisa” turns into “Johnny crushed Lisa.”

My inner physician, elbowing the nervous parent aside, asked about the evidence for an aspiration. “The X-ray was negative, as was the exam, but the history suggests aspiration,” the ENT told me.

“What history?” I asked.

“That he has a history of ‘tonguing’ vitamins,” he said.

“Tonguing vitamins?” I responded, incredulously feeling the need to defend my child’s pill-swallowing honor. “Where did that story come from? We aren’t even sure we gave him a vitamin tonight.”

Nonetheless, the ENT was confident that “kids aspirate things all the time.”

Skeptical, I continued the debate. “But what if we hadn’t given that history? Would you still think of aspiration in this case?”

“Probably not, but then you did give us that history,” he replied. “So we need to bronch him.”

Culprit Revealed

Meanwhile, Grey was looking better with supplemental oxygen and a nebulizer’s worth of racemic epinephrine. His stridor took on more of a “barking seal” nature, and 30 minutes later, he developed a fever characteristic of croup. After a dose of steroids and another whiff of racemic epi, he was himself again, laughing the laugh of a wounded seal at the pulse oximeter, which backlit his big toe red. Comedy-club-level laughter replaced the look of death in the matter of an hour, as I was reminded of the resiliency of children. If only Mom and Dad could capture a bit of that.

Feeling a cocktail of relief and embarrassment—how could two physicians misdiagnose croup as an aspirated foreign body?—we readied ourselves for discharge. Just then, the ENT doctor came back in and told us the OR would be ready in a few hours. “But,” I inquired, “isn’t this just croup?”

“Most likely,” he replied, “but we can’t rule out aspiration without a bronchoscopy.”

It was then that I realized we (and our medical team) had fallen victim to some common heuristical errors. Heuristics are those little shortcuts in logic that we utilize to solve common problems. They are bred from years of experience and helpfully get us home every night in time for dinner. Without them, medicine would be a painstaking, Everlasting Gobstopper-like journey through endless differential diagnoses—in other words, your four-hour clerkship patient evaluations in medical school.

These shortcuts allow us to quickly recognize that a diaphoretic, 60-year-old man with diabetes, hyperlipidemia, and substernal chest pain has an acute coronary syndrome. We don’t spend hours thinking of Tietze’s syndrome, Boerhaave’s disease, and their ilk, because our mind quickly takes the shortcut to the right diagnosis. Although helpful, these shortcuts can cut both ways, occasionally resulting in thrombolytic therapy for an aortic dissection.

This is where Grey’s situation went wrong. My wife and I were victimized by the availability bias. This cognitive bias occurs when a recently encountered situation is given undue stature solely because of its proximity in time to the next event—i.e., it is “available.” So, because my son choked on a vitamin the night before, he must be choking on a vitamin the next night. (Even though we didn’t give him a vitamin and hours had passed since we put him to bed.) There is little connection between the two events, outside of the fact that aspiration is at the fore of your mind. This happens to us all the time. Think about the last presentation you attended about an obscure topic, only to amazingly find that the very next day, you had not one but two patients who surely required a workup for acute intermittent porphyria.

Common Practices

Anchoring bias is another common cognitive error in which we overly rely on one piece of information, the “anchor.” This was certainly in play during our ED visit. The mere mention of an aspirated foreign body was latched on to immediately. From there, tidbits of information that supported that diagnosis (something in the back of his throat on our exam, kids aspirate all the time) were kept, while the unsupporting evidence (negative X-ray and exam findings, fever, barking cough that awakes a kid at night) was jettisoned.

We fell prey to the momentum bias. This heuristical hiccup frequently wreaks cross-coverage havoc. You’ve seen this, I’m sure. Because the day team thought the renal failure was due to prerenal azotemia, the night team harmonizes, continuing to treat the patient’s bladder outlet obstruction with volume challenges. That is until someone—in my sphere, it’s usually the third-year medical student—asks if this could all be from the patient’s benign prostatic hyperplasia and medications.

After convincing our well-intentioned ENT colleague to call off the bronch, I was left with the important lesson that the ways in which our minds work, also well-intentioned, can cause us fits of trouble. I was left with the realization that the only way to mitigate the risk these cognitive shortcuts pose is to be constantly vigilant of their presence.

And, perhaps most importantly, I was left with an overstimulated 2-year-old high on the excitement of a hospital visit and large doses of adrenaline—a combination that left me desperately yearning for silence. TH

Dr. Glasheen is The Hospitalist’s physician editor.

With the growth of HM has come a major change in the way healthcare is delivered in hospitals across the country: Hospitalists have become one of the major providers of care for hospitalized medical patients. Recent reports suggest that hospitalists care for more than 50% of Medicare patients admitted with a medical diagnosis. In addition to that staggering figure, hospitalists increasingly have assumed care for many surgical patients, have staffed observation units, created procedure services, assumed care of many subspecialty services, and have taken the lead on hospital-based IT and quality-improvement (QI) endeavors, among other key services.

It is hard to argue against the assertion that HM’s emergence over the past decade and a half is one of the most significant game-changers in all of healthcare. Despite this important impact on the structure of care delivery, HM to date has fallen short of the contributions made by many other disciplines over the years in one key area: the generation of new knowledge through research.

New Specialties’ Research Focus

Think for a minute of the contributions of the next two youngest specialties—critical-care medicine and emergency medicine. Both fields have transformed care delivery, as did HM, but in contrast, both critical-care and emergency medicine have well-established investigators and an impressive research agenda. They have had a major impact on the care of patients everywhere.

For example, the critical-care community developed new treatment paradigms for sepsis that grew out of basic science work exploring the roles of cytokines and the inflammatory cascade in infection. Its clinical-research networks have developed and tested new ventilator- and fluid-management strategies for acute respiratory distress syndrome.

Similarly, the emergency medicine community has developed new algorithms for the treatment of cardiac arrest, trauma, and many other common emergency diagnoses that are now implemented in EDs all over the country.

We, the HM community, should aspire to do the same.

By saying we need to do more, I do not mean to undermine the many important contributions we are making. Just pick up any issue of the Journal of Hospital Medicine, and you will find a wealth of literature describing the important work of hospitalists everywhere. But to have a lasting impact, we need to continue to expand on this work to advance the national health research agenda by having hospitalists pursue clinical and comparative-effectiveness research, quality and safety research, health system innovations work, and even basic science research.

Research Assistance

SHM has always prided itself in being at the forefront of training and networking opportunities for hospitalists. It should come as no surprise that SHM continues to lead in the creation of opportunities designed to enhance HM research.

To advance the research agenda, we need to advance researchers. HM researchers struggle to find funding for their work in a federal infrastructure that emphasizes disease- and organ-based investigation. A hospitalist investigator often explores areas that cross disease boundaries, or pursues work that falls into the realm of “quality and safety,” which tends to have fewer funding opportunities. Hospitalist investigators need a hand getting started, and SHM is going to lend that hand.

At HM10 this month in Washington, D.C., we will announce the recipients of the newly created SHM Junior Faculty Development Award. The award will provide two recipients with $25,000 per year for two consecutive years. This award is a mentored research award, which means it is intended to support junior hospitalist faculty as they apply for a research career development award. The goal in creating this award is to fulfill SHM’s mission of promoting excellence in the practice of HM through research, and to build a generation of effective hospitalist researchers who can define and explore questions pertinent to the general medical care of hospitalized patients.

We hope these awards, through funding and mentoring, boost successful hospitalist investigators, grow the number of hospitalist-initiated research projects, and show academic institutions that hospitalist research ideas have merit. It also is likely that, over time, the awards will create a network of SHM-funded investigators whose collaboration and interaction will further accelerate HM research.

Our hope is that this effort benefits not just the investigators receiving the money, but also all practicing hospitalists and their patients by further clarifying the best methods to care for hospitalized patients, by creating new treatment paradigms, and advancing the science of HM for the benefit of all.

Please join me in congratulating the recipients of this important and prestigious award. TH

Dr. Flanders is president of SHM.

With the growth of HM has come a major change in the way healthcare is delivered in hospitals across the country: Hospitalists have become one of the major providers of care for hospitalized medical patients. Recent reports suggest that hospitalists care for more than 50% of Medicare patients admitted with a medical diagnosis. In addition to that staggering figure, hospitalists increasingly have assumed care for many surgical patients, have staffed observation units, created procedure services, assumed care of many subspecialty services, and have taken the lead on hospital-based IT and quality-improvement (QI) endeavors, among other key services.

It is hard to argue against the assertion that HM’s emergence over the past decade and a half is one of the most significant game-changers in all of healthcare. Despite this important impact on the structure of care delivery, HM to date has fallen short of the contributions made by many other disciplines over the years in one key area: the generation of new knowledge through research.

New Specialties’ Research Focus

Think for a minute of the contributions of the next two youngest specialties—critical-care medicine and emergency medicine. Both fields have transformed care delivery, as did HM, but in contrast, both critical-care and emergency medicine have well-established investigators and an impressive research agenda. They have had a major impact on the care of patients everywhere.

For example, the critical-care community developed new treatment paradigms for sepsis that grew out of basic science work exploring the roles of cytokines and the inflammatory cascade in infection. Its clinical-research networks have developed and tested new ventilator- and fluid-management strategies for acute respiratory distress syndrome.

Similarly, the emergency medicine community has developed new algorithms for the treatment of cardiac arrest, trauma, and many other common emergency diagnoses that are now implemented in EDs all over the country.

We, the HM community, should aspire to do the same.

By saying we need to do more, I do not mean to undermine the many important contributions we are making. Just pick up any issue of the Journal of Hospital Medicine, and you will find a wealth of literature describing the important work of hospitalists everywhere. But to have a lasting impact, we need to continue to expand on this work to advance the national health research agenda by having hospitalists pursue clinical and comparative-effectiveness research, quality and safety research, health system innovations work, and even basic science research.

Research Assistance

SHM has always prided itself in being at the forefront of training and networking opportunities for hospitalists. It should come as no surprise that SHM continues to lead in the creation of opportunities designed to enhance HM research.

To advance the research agenda, we need to advance researchers. HM researchers struggle to find funding for their work in a federal infrastructure that emphasizes disease- and organ-based investigation. A hospitalist investigator often explores areas that cross disease boundaries, or pursues work that falls into the realm of “quality and safety,” which tends to have fewer funding opportunities. Hospitalist investigators need a hand getting started, and SHM is going to lend that hand.

At HM10 this month in Washington, D.C., we will announce the recipients of the newly created SHM Junior Faculty Development Award. The award will provide two recipients with $25,000 per year for two consecutive years. This award is a mentored research award, which means it is intended to support junior hospitalist faculty as they apply for a research career development award. The goal in creating this award is to fulfill SHM’s mission of promoting excellence in the practice of HM through research, and to build a generation of effective hospitalist researchers who can define and explore questions pertinent to the general medical care of hospitalized patients.

We hope these awards, through funding and mentoring, boost successful hospitalist investigators, grow the number of hospitalist-initiated research projects, and show academic institutions that hospitalist research ideas have merit. It also is likely that, over time, the awards will create a network of SHM-funded investigators whose collaboration and interaction will further accelerate HM research.

Our hope is that this effort benefits not just the investigators receiving the money, but also all practicing hospitalists and their patients by further clarifying the best methods to care for hospitalized patients, by creating new treatment paradigms, and advancing the science of HM for the benefit of all.

Please join me in congratulating the recipients of this important and prestigious award. TH

Dr. Flanders is president of SHM.

With the growth of HM has come a major change in the way healthcare is delivered in hospitals across the country: Hospitalists have become one of the major providers of care for hospitalized medical patients. Recent reports suggest that hospitalists care for more than 50% of Medicare patients admitted with a medical diagnosis. In addition to that staggering figure, hospitalists increasingly have assumed care for many surgical patients, have staffed observation units, created procedure services, assumed care of many subspecialty services, and have taken the lead on hospital-based IT and quality-improvement (QI) endeavors, among other key services.

It is hard to argue against the assertion that HM’s emergence over the past decade and a half is one of the most significant game-changers in all of healthcare. Despite this important impact on the structure of care delivery, HM to date has fallen short of the contributions made by many other disciplines over the years in one key area: the generation of new knowledge through research.

New Specialties’ Research Focus

Think for a minute of the contributions of the next two youngest specialties—critical-care medicine and emergency medicine. Both fields have transformed care delivery, as did HM, but in contrast, both critical-care and emergency medicine have well-established investigators and an impressive research agenda. They have had a major impact on the care of patients everywhere.

For example, the critical-care community developed new treatment paradigms for sepsis that grew out of basic science work exploring the roles of cytokines and the inflammatory cascade in infection. Its clinical-research networks have developed and tested new ventilator- and fluid-management strategies for acute respiratory distress syndrome.

Similarly, the emergency medicine community has developed new algorithms for the treatment of cardiac arrest, trauma, and many other common emergency diagnoses that are now implemented in EDs all over the country.

We, the HM community, should aspire to do the same.

By saying we need to do more, I do not mean to undermine the many important contributions we are making. Just pick up any issue of the Journal of Hospital Medicine, and you will find a wealth of literature describing the important work of hospitalists everywhere. But to have a lasting impact, we need to continue to expand on this work to advance the national health research agenda by having hospitalists pursue clinical and comparative-effectiveness research, quality and safety research, health system innovations work, and even basic science research.

Research Assistance

SHM has always prided itself in being at the forefront of training and networking opportunities for hospitalists. It should come as no surprise that SHM continues to lead in the creation of opportunities designed to enhance HM research.

To advance the research agenda, we need to advance researchers. HM researchers struggle to find funding for their work in a federal infrastructure that emphasizes disease- and organ-based investigation. A hospitalist investigator often explores areas that cross disease boundaries, or pursues work that falls into the realm of “quality and safety,” which tends to have fewer funding opportunities. Hospitalist investigators need a hand getting started, and SHM is going to lend that hand.

At HM10 this month in Washington, D.C., we will announce the recipients of the newly created SHM Junior Faculty Development Award. The award will provide two recipients with $25,000 per year for two consecutive years. This award is a mentored research award, which means it is intended to support junior hospitalist faculty as they apply for a research career development award. The goal in creating this award is to fulfill SHM’s mission of promoting excellence in the practice of HM through research, and to build a generation of effective hospitalist researchers who can define and explore questions pertinent to the general medical care of hospitalized patients.

We hope these awards, through funding and mentoring, boost successful hospitalist investigators, grow the number of hospitalist-initiated research projects, and show academic institutions that hospitalist research ideas have merit. It also is likely that, over time, the awards will create a network of SHM-funded investigators whose collaboration and interaction will further accelerate HM research.

Our hope is that this effort benefits not just the investigators receiving the money, but also all practicing hospitalists and their patients by further clarifying the best methods to care for hospitalized patients, by creating new treatment paradigms, and advancing the science of HM for the benefit of all.

Please join me in congratulating the recipients of this important and prestigious award. TH

Dr. Flanders is president of SHM.

Whether pure political theater or a real attempt at bipartisanship, the Feb. 25 healthcare summit was a milestone on the way to March’s riveting Congressional vote in favor of healtcare reform.

Both parties arrived with some newly dusted off—or slightly tweaked—ideas to throw into the mix, in part to give voters the impression that they knew best how to move forward with healthcare reform. In the end, the legislation that narrowly prevailed March 20 incorporated some of those ideas while dumping or reshaping others (items in the reconciliation bill weren’t finalized at press time).

The fight isn’t over, however, and we are likely to hear the same dueling themes again: more federal government intervention versus more market-driven solutions for addressing access and cost. Most of the ideas influence hospital care, frequently cited as one of the most expensive sectors of healthcare. Here’s a look at key proposals that rose to the top of their parties’ wish lists in February, and how they fared in March.

Idea: Allow People to Buy Health Insurance across State Lines

Although not new, Republican legislators revived the idea bandied about during the Bush administration, and made it a key element of their alternative to the Democratic plan. Ultimately, it would hold insurance companies accountable through robust competition, but without a “federal bureaucracy,” Rep. Marsha Blackburn (R-Tenn.) said at the summit. With competition fueling reduced insurance premiums for consumers, the argument goes, the number of insured increases.

Michael Cousineau, an associate professor of research at the University of Southern California and a specialist in health policy and health services, isn’t having it. “I think that it’s a stupid proposal,” he says. First, he argues, it’s not practical for someone in California to buy a policy from Mississippi. If a consumer has a problem with an out-of-state health plan refusing to cover care, he asks, “who are you going to complain to?”

If insurance companies set up shop in the states with the lowest level of regulation, he says, younger and healthier adults would migrate to those cheaper plans, leaving the older and sicker adults who really need healthcare in plans with the strongest consumer protections. “So you’ll end up with this massive problem of sick people in some plans and well people in the other plans, and it’s just going to create havoc. I don’t think it’s a sustainable mechanism,” he says. Doctors, hospitals, and even insurers themselves would hate it, he says, because of the massive influx of out-of-state insurance companies.

Democrats, including Oregon Sen. Ron Wyden, introduced their own version of the proposal, but on a more regional level and with more rigorous oversight. Currently, insurance plans must meet the requirements of the states in which they’re sold. But states have incredibly varied mandates about what kind of healthcare must be covered. “If you permit the interstate sales of insurance under the current plans, then more or less all of those state rules go out the door,” says Leighton Ku, a health policy analyst at George Washington University. Although sidestepping state-specific regulations would permit people to buy insurance from the state with the cheapest plan, he says, “in many cases, that would be because the state has the fewest restrictions on it.”

And therein lies another big concern, he says: “That it essentially begins to create a race to the bottom.”

At the summit, President Obama supported selling insurance across state lines, but through a national exchange with at least “minimal standards” through which any insurer could participate.

Ultimately, the new legislation will allow states to form exchanges, but with an option for regional exchanges as well.

Idea: Create a Health Insurance Rate Authority

Championed by Obama, this proposal arrived on the heels of several high-profile rate increases that have generated considerable public angst. Not coincidentally, the House Energy and Commerce Committee held a hearing about soaring premiums the day before the summit.

At the hearing, legislators questioned Wellpoint president and CEO Angela Braly about the company’s Anthem Blue Cross unit and its plans to raise insurance premiums by as much as 39% for some Californians (overall, premium increases average 25%). Braly, in turn, blamed the surge on rising and “unsustainable” pharmacy and hospital care costs, the latter driven primarily by hospital reimbursement rates.

Although the general concept of federal oversight is useful, Ku says, the big question is one of authority. Regulating insurers has traditionally fallen to state governments, which likely will be reluctant to give up jurisdictional power but might accept federal assistance.

“I think in general it would help, but I don’t think it’s going to have as much of an impact unless we control the cost-of-care downlink,” Cousineau adds. Including a mandate for individuals to buy health insurance reduces the need for the authority, though he concedes that some cynics doubt whether health insurers will voluntarily lower rates even if more young, healthy people buy policies. Republicans oppose the idea of an individual mandate and a new federal regulatory entity.

In the March bill, the individual mandate prevailed while the idea of a new insurance watchdog fell by the wayside.

Idea: Provide State Grants to Expand High-Risk Pools for Uninsured

The idea, proposed by Republicans in several iterations, including Sen. John McCain (R-Ariz.) when he ran for president, was offered as a potential alternative to banning insurance companies from denying coverage to patients with pre-existing conditions. Many states already offer high-risk patient pools for patients who have been excluded from the private market, but some have long waiting lists. The Health Insurance Plan of California (HPIC), for example, has a two-year wait, according to Cousineau.

“It’s not a bad idea,” he says of a federal subsidy, but because the pools only include high-risk patients, he says they won’t solve the problem of expensive premiums. Cousineau prefers state-based exchanges that aren’t segregated by risk and spread the cost over a wider range of people, which is included in the March bill. “Otherwise, it’s too expensive, and you’re asking the states to pay for part of it,” he says.

Ku believes high-risk pools could deliver some relief to patients currently priced out of the market. “It’s not going to help the neediest of the needy, but could help some,” he says. As a temporary fix, the new legislation sets up high-risk pools in states that lack them, with $5 billion from the federal coffers. The mechanism will be phased out in 2014, however; by then, all insurers will be banned from denying coverage to anyone.

Idea: Gradually Close the “Doughnut Hole”

An idea popular with senior citizens, closing the gap in Medicare’s Part D prescription drug coverage gained further traction under Obama’s healthcare plan and was included in the healthcare reconciliation bill. The doughnut-hole closure is paid for with savings from cuts to the Medicare Advantage program.

Experts question whether it will affect as many patients as has been widely assumed. “I think it’s an important thing to do,” Cousineau says, “but I’m not as worried as much about the costs there as I am in other parts of the program.”

Uncertainties aside, closing Medicare’s doughnut hole could help ease at least one headache cited by hospitalists: struggling to sort through hospitalized patients’ formularies to insure they can afford the drugs they need upon discharge—so they won’t end up back in the hospital. TH

Bryn Nelson is a freelance medical writer based in Seattle.

Whether pure political theater or a real attempt at bipartisanship, the Feb. 25 healthcare summit was a milestone on the way to March’s riveting Congressional vote in favor of healtcare reform.

Both parties arrived with some newly dusted off—or slightly tweaked—ideas to throw into the mix, in part to give voters the impression that they knew best how to move forward with healthcare reform. In the end, the legislation that narrowly prevailed March 20 incorporated some of those ideas while dumping or reshaping others (items in the reconciliation bill weren’t finalized at press time).

The fight isn’t over, however, and we are likely to hear the same dueling themes again: more federal government intervention versus more market-driven solutions for addressing access and cost. Most of the ideas influence hospital care, frequently cited as one of the most expensive sectors of healthcare. Here’s a look at key proposals that rose to the top of their parties’ wish lists in February, and how they fared in March.

Idea: Allow People to Buy Health Insurance across State Lines

Although not new, Republican legislators revived the idea bandied about during the Bush administration, and made it a key element of their alternative to the Democratic plan. Ultimately, it would hold insurance companies accountable through robust competition, but without a “federal bureaucracy,” Rep. Marsha Blackburn (R-Tenn.) said at the summit. With competition fueling reduced insurance premiums for consumers, the argument goes, the number of insured increases.

Michael Cousineau, an associate professor of research at the University of Southern California and a specialist in health policy and health services, isn’t having it. “I think that it’s a stupid proposal,” he says. First, he argues, it’s not practical for someone in California to buy a policy from Mississippi. If a consumer has a problem with an out-of-state health plan refusing to cover care, he asks, “who are you going to complain to?”

If insurance companies set up shop in the states with the lowest level of regulation, he says, younger and healthier adults would migrate to those cheaper plans, leaving the older and sicker adults who really need healthcare in plans with the strongest consumer protections. “So you’ll end up with this massive problem of sick people in some plans and well people in the other plans, and it’s just going to create havoc. I don’t think it’s a sustainable mechanism,” he says. Doctors, hospitals, and even insurers themselves would hate it, he says, because of the massive influx of out-of-state insurance companies.

Democrats, including Oregon Sen. Ron Wyden, introduced their own version of the proposal, but on a more regional level and with more rigorous oversight. Currently, insurance plans must meet the requirements of the states in which they’re sold. But states have incredibly varied mandates about what kind of healthcare must be covered. “If you permit the interstate sales of insurance under the current plans, then more or less all of those state rules go out the door,” says Leighton Ku, a health policy analyst at George Washington University. Although sidestepping state-specific regulations would permit people to buy insurance from the state with the cheapest plan, he says, “in many cases, that would be because the state has the fewest restrictions on it.”

And therein lies another big concern, he says: “That it essentially begins to create a race to the bottom.”

At the summit, President Obama supported selling insurance across state lines, but through a national exchange with at least “minimal standards” through which any insurer could participate.

Ultimately, the new legislation will allow states to form exchanges, but with an option for regional exchanges as well.

Idea: Create a Health Insurance Rate Authority

Championed by Obama, this proposal arrived on the heels of several high-profile rate increases that have generated considerable public angst. Not coincidentally, the House Energy and Commerce Committee held a hearing about soaring premiums the day before the summit.

At the hearing, legislators questioned Wellpoint president and CEO Angela Braly about the company’s Anthem Blue Cross unit and its plans to raise insurance premiums by as much as 39% for some Californians (overall, premium increases average 25%). Braly, in turn, blamed the surge on rising and “unsustainable” pharmacy and hospital care costs, the latter driven primarily by hospital reimbursement rates.

Although the general concept of federal oversight is useful, Ku says, the big question is one of authority. Regulating insurers has traditionally fallen to state governments, which likely will be reluctant to give up jurisdictional power but might accept federal assistance.

“I think in general it would help, but I don’t think it’s going to have as much of an impact unless we control the cost-of-care downlink,” Cousineau adds. Including a mandate for individuals to buy health insurance reduces the need for the authority, though he concedes that some cynics doubt whether health insurers will voluntarily lower rates even if more young, healthy people buy policies. Republicans oppose the idea of an individual mandate and a new federal regulatory entity.

In the March bill, the individual mandate prevailed while the idea of a new insurance watchdog fell by the wayside.

Idea: Provide State Grants to Expand High-Risk Pools for Uninsured

The idea, proposed by Republicans in several iterations, including Sen. John McCain (R-Ariz.) when he ran for president, was offered as a potential alternative to banning insurance companies from denying coverage to patients with pre-existing conditions. Many states already offer high-risk patient pools for patients who have been excluded from the private market, but some have long waiting lists. The Health Insurance Plan of California (HPIC), for example, has a two-year wait, according to Cousineau.

“It’s not a bad idea,” he says of a federal subsidy, but because the pools only include high-risk patients, he says they won’t solve the problem of expensive premiums. Cousineau prefers state-based exchanges that aren’t segregated by risk and spread the cost over a wider range of people, which is included in the March bill. “Otherwise, it’s too expensive, and you’re asking the states to pay for part of it,” he says.

Ku believes high-risk pools could deliver some relief to patients currently priced out of the market. “It’s not going to help the neediest of the needy, but could help some,” he says. As a temporary fix, the new legislation sets up high-risk pools in states that lack them, with $5 billion from the federal coffers. The mechanism will be phased out in 2014, however; by then, all insurers will be banned from denying coverage to anyone.

Idea: Gradually Close the “Doughnut Hole”

An idea popular with senior citizens, closing the gap in Medicare’s Part D prescription drug coverage gained further traction under Obama’s healthcare plan and was included in the healthcare reconciliation bill. The doughnut-hole closure is paid for with savings from cuts to the Medicare Advantage program.

Experts question whether it will affect as many patients as has been widely assumed. “I think it’s an important thing to do,” Cousineau says, “but I’m not as worried as much about the costs there as I am in other parts of the program.”

Uncertainties aside, closing Medicare’s doughnut hole could help ease at least one headache cited by hospitalists: struggling to sort through hospitalized patients’ formularies to insure they can afford the drugs they need upon discharge—so they won’t end up back in the hospital. TH

Bryn Nelson is a freelance medical writer based in Seattle.

Whether pure political theater or a real attempt at bipartisanship, the Feb. 25 healthcare summit was a milestone on the way to March’s riveting Congressional vote in favor of healtcare reform.

Both parties arrived with some newly dusted off—or slightly tweaked—ideas to throw into the mix, in part to give voters the impression that they knew best how to move forward with healthcare reform. In the end, the legislation that narrowly prevailed March 20 incorporated some of those ideas while dumping or reshaping others (items in the reconciliation bill weren’t finalized at press time).

The fight isn’t over, however, and we are likely to hear the same dueling themes again: more federal government intervention versus more market-driven solutions for addressing access and cost. Most of the ideas influence hospital care, frequently cited as one of the most expensive sectors of healthcare. Here’s a look at key proposals that rose to the top of their parties’ wish lists in February, and how they fared in March.

Idea: Allow People to Buy Health Insurance across State Lines

Although not new, Republican legislators revived the idea bandied about during the Bush administration, and made it a key element of their alternative to the Democratic plan. Ultimately, it would hold insurance companies accountable through robust competition, but without a “federal bureaucracy,” Rep. Marsha Blackburn (R-Tenn.) said at the summit. With competition fueling reduced insurance premiums for consumers, the argument goes, the number of insured increases.

Michael Cousineau, an associate professor of research at the University of Southern California and a specialist in health policy and health services, isn’t having it. “I think that it’s a stupid proposal,” he says. First, he argues, it’s not practical for someone in California to buy a policy from Mississippi. If a consumer has a problem with an out-of-state health plan refusing to cover care, he asks, “who are you going to complain to?”

If insurance companies set up shop in the states with the lowest level of regulation, he says, younger and healthier adults would migrate to those cheaper plans, leaving the older and sicker adults who really need healthcare in plans with the strongest consumer protections. “So you’ll end up with this massive problem of sick people in some plans and well people in the other plans, and it’s just going to create havoc. I don’t think it’s a sustainable mechanism,” he says. Doctors, hospitals, and even insurers themselves would hate it, he says, because of the massive influx of out-of-state insurance companies.

Democrats, including Oregon Sen. Ron Wyden, introduced their own version of the proposal, but on a more regional level and with more rigorous oversight. Currently, insurance plans must meet the requirements of the states in which they’re sold. But states have incredibly varied mandates about what kind of healthcare must be covered. “If you permit the interstate sales of insurance under the current plans, then more or less all of those state rules go out the door,” says Leighton Ku, a health policy analyst at George Washington University. Although sidestepping state-specific regulations would permit people to buy insurance from the state with the cheapest plan, he says, “in many cases, that would be because the state has the fewest restrictions on it.”

And therein lies another big concern, he says: “That it essentially begins to create a race to the bottom.”

At the summit, President Obama supported selling insurance across state lines, but through a national exchange with at least “minimal standards” through which any insurer could participate.

Ultimately, the new legislation will allow states to form exchanges, but with an option for regional exchanges as well.

Idea: Create a Health Insurance Rate Authority

Championed by Obama, this proposal arrived on the heels of several high-profile rate increases that have generated considerable public angst. Not coincidentally, the House Energy and Commerce Committee held a hearing about soaring premiums the day before the summit.

At the hearing, legislators questioned Wellpoint president and CEO Angela Braly about the company’s Anthem Blue Cross unit and its plans to raise insurance premiums by as much as 39% for some Californians (overall, premium increases average 25%). Braly, in turn, blamed the surge on rising and “unsustainable” pharmacy and hospital care costs, the latter driven primarily by hospital reimbursement rates.

Although the general concept of federal oversight is useful, Ku says, the big question is one of authority. Regulating insurers has traditionally fallen to state governments, which likely will be reluctant to give up jurisdictional power but might accept federal assistance.

“I think in general it would help, but I don’t think it’s going to have as much of an impact unless we control the cost-of-care downlink,” Cousineau adds. Including a mandate for individuals to buy health insurance reduces the need for the authority, though he concedes that some cynics doubt whether health insurers will voluntarily lower rates even if more young, healthy people buy policies. Republicans oppose the idea of an individual mandate and a new federal regulatory entity.

In the March bill, the individual mandate prevailed while the idea of a new insurance watchdog fell by the wayside.

Idea: Provide State Grants to Expand High-Risk Pools for Uninsured

The idea, proposed by Republicans in several iterations, including Sen. John McCain (R-Ariz.) when he ran for president, was offered as a potential alternative to banning insurance companies from denying coverage to patients with pre-existing conditions. Many states already offer high-risk patient pools for patients who have been excluded from the private market, but some have long waiting lists. The Health Insurance Plan of California (HPIC), for example, has a two-year wait, according to Cousineau.

“It’s not a bad idea,” he says of a federal subsidy, but because the pools only include high-risk patients, he says they won’t solve the problem of expensive premiums. Cousineau prefers state-based exchanges that aren’t segregated by risk and spread the cost over a wider range of people, which is included in the March bill. “Otherwise, it’s too expensive, and you’re asking the states to pay for part of it,” he says.

Ku believes high-risk pools could deliver some relief to patients currently priced out of the market. “It’s not going to help the neediest of the needy, but could help some,” he says. As a temporary fix, the new legislation sets up high-risk pools in states that lack them, with $5 billion from the federal coffers. The mechanism will be phased out in 2014, however; by then, all insurers will be banned from denying coverage to anyone.

Idea: Gradually Close the “Doughnut Hole”

An idea popular with senior citizens, closing the gap in Medicare’s Part D prescription drug coverage gained further traction under Obama’s healthcare plan and was included in the healthcare reconciliation bill. The doughnut-hole closure is paid for with savings from cuts to the Medicare Advantage program.

Experts question whether it will affect as many patients as has been widely assumed. “I think it’s an important thing to do,” Cousineau says, “but I’m not as worried as much about the costs there as I am in other parts of the program.”

Uncertainties aside, closing Medicare’s doughnut hole could help ease at least one headache cited by hospitalists: struggling to sort through hospitalized patients’ formularies to insure they can afford the drugs they need upon discharge—so they won’t end up back in the hospital. TH

Bryn Nelson is a freelance medical writer based in Seattle.

Case

A 56-year-old man with a history of cirrhosis, complicated by esophageal varices and ongoing alcohol abuse, is admitted after his wife found him lethargic and disoriented in bed. His wife said he’d been increasingly irritable and agitated, with slurred speech, the past two days. On exam, he is somnolent but arousable; spider telangiectasias and asterixis are noted. Laboratory studies are consistent with chronic liver disease.

What is the best therapy for his acute hepatic encephalopathy?

Overview

Hepatic encephalopathy (HE) describes the spectrum of potentially reversible neuropsychiatric abnormalities seen in patients with liver dysfunction. The wide range of neuropsychiatric presentations led to the development of consensus HE classification terminology by the World Congress of Gastroenterology in 2002.

The primary tenet of all HE pathogenesis theories is firmly established: Nitrogenous substances derived from the gut adversely affect brain function. These compounds access the systemic circulation via decreased hepatic function or portal-systemic shunts. In the brain, they alter neurotransmission, which affects consciousness and behavior.

HE patients usually have advanced cirrhosis and, hence, many of the physical findings associated with severe hepatic dysfunction: muscle-wasting, jaundice, ascites, palmar erythema, edema, spider telangiectasias, and fetor hepaticus. Encephalopathy progresses from reversal of the sleep-wake cycle and mild mental status changes to irritability, confusion, and slurred speech.

Advanced neurologic features include asterixis or tongue fasciculations, bradykinesia, hyperreflexia, and ultimately coma. History and laboratory data can reveal a precipitating cause (see Table 2, p. 19). Measurement of ammonia concentration remains controversial. The value may be useful for monitoring the efficacy of ammonia-lowering therapy, but elevated levels are not required to make the diagnosis.

Multiple treatments have been used to manage HE, yet few well-designed randomized trials have assessed efficacy due to challenges inherent in measuring the wide range of neuropsychiatric presentations. Nonetheless, a critical appraisal of available data delineates a rational approach to therapy.

Review of the Data

click for large version

In addition to supportive care and the reversal of any precipitating factors, the treatment of acute HE is aimed at reducing or inhibiting intestinal ammonia production or increasing its removal (see Table 1, left).

Nonabsorbable disaccharides (NAD): Lactulose (beta-galactosidofructose) and lactitol (beta-galactosidosorbitol) are used as first-line agents for the treatment of HE and lead to symptomatic improvement in 67% to 87% of patients.1 They reduce the concentration of ammoniogenic substrates in the colonic lumen in two ways—first, by facilitating bacterial fermentation and secondary organic acid production (lowering colonic pH) and, second, by direct osmotic catharsis.

NAD are administered orally or via nasogastric tube at an initial dose of 45 ml, followed by repeated hourly doses until the patient has a bowel movement. For patients at risk of aspiration, NAD can be administered via enema (300 ml in 700 ml of water) every two hours as needed until mental function improves. Once the risk of aspiration is minimized, NAD can be administered orally and titrated to achieve two to three soft bowel movements daily (the usual oral dosage is 15 ml to 45 ml every eight to 12 hours).

Common side effects of NAD include an excessively sweet taste, flatulence, abdominal cramping, and electrolyte imbalance, particularly hypernatremia, which may further deteriorate mental status.

click for large version

Als-Nielsen et al demonstrated in a systematic review that NAD were more effective than placebo in improving HE, but NAD had no significant benefit on mortality.1 However, the effect on HE no longer reached statistical significance when the analysis was confined to studies with the highest methodological quality. In a randomized, double-blind comparison, Morgan et al showed that lactitol was more tolerable than lactulose and produced fewer side effects.2 Lactitol is not currently available for use in the U.S.

Antibiotics: Certain oral antibiotics (e.g., neomycin, rifaximin, and metronidazole) reduce urease-producing intestinal bacteria, which results in decreased ammonia production and absorption through the gastrointestinal tract. Antibiotics generally are used in patients who do not tolerate NAD or who remain symptomatic despite NAD. The combined use of NAD and antibiotics is a subject of significant clinical relevance, though data are limited.

Neomycin is approved by the FDA for treatment of acute HE. It can be administered orally at a dose of 1,000 mg every six hours for up to six days. A randomized, controlled trial of neomycin versus placebo in 39 patients with acute HE demonstrated no significant difference in time to symptom improvement.3 Another study of 80 patients receiving neomycin and lactulose demonstrated no benefit against placebo, though some data suggest that the combination of lactulose and neomycin therapy might be more effective than either agent alone against placebo.4

Rifaximin was granted an orphan drug designation by the FDA for use in HE cases and has been compared with NAD. The recommended dose is 1,200 mg three times per day. It has minimal side effects and no reported drug interactions. A study of rifaximin versus lactitol administered for five to 10 days showed approximately 80% symptomatic improvement in both groups.5 Another trial demonstrated significantly greater improvement in blood ammonia concentrations, electroencephalographic (EEG) abnormalities, and mental status with rifaximin compared with lactulose.6 Studies comparing rifaximin and lactulose, either alone or in combination, have demonstrated that rifaximin is at least similar to lactulose, and in some cases superior in reversing encephalopathy, with better tolerability reported in the antibiotic group.7

Metronidazole is not approved by the FDA for the treatment of HE but has been evaluated. The recommended oral dose of metronidazole for chronic use is 250 mg twice per day. Prolonged administration of metronidazole can be associated with gastrointestinal disturbance and neurotoxicity. In a report of 11 HE patients with mild to moderate symptoms and seven chronically affected HE cirrhotic patients treated with metronidazole for one week, Morgan and colleagues showed metronidazole to be as effective as neomycin.8

Diet: Historically, patients with HE were placed on protein-restricted diets to reduce the production of intestinal ammonia. Recent evidence suggests that excessive restriction can raise serum ammonia levels as a result of reduced muscular ammonia metabolism. Furthermore, restricting protein intake worsens nutritional status and does not improve the outcome.9

In patients with established cirrhosis, the minimal daily dietary protein intake required to maintain nitrogen balance is 0.8 g/kg to 1.0 g/kg. At this time, a normoprotein diet for HE patients is considered the standard of care.

Other agents: L-ornithine L-aspartate (LOLA), a stable salt of ornithine and aspartic acid, provides crucial substrates for glutamine and urea synthesis—key pathways in deammonation. In patients with cirrhosis and HE, oral LOLA reduces serum ammonia and improves clinical manifestations of HE, including EEG abnormalities.10 LOLA, however, is not available in the U.S.

Sodium benzoate might be beneficial in the treatment of acute HE; it increases urinary excretion of ammonia. A prospective, randomized, double-blind study of 74 patients with acute HE found that treatment with sodium benzoate 5 g twice daily, compared with lactulose, resulted in equivalent improvements in encephalopathy. There was no placebo group.11 Routine use has been limited due to concerns regarding sodium load and increased frequency of adverse gastrointestinal symptoms, particularly nausea.

Flumazenil, a short-acting benzodiazepine receptor antagonist, has been utilized on the basis of observed increases in benzodiazepine receptor activation among cirrhotic HE patients. In a systematic review of 12 controlled trials (765 patients), Als-Nielsen and colleagues found flumazenil to be associated with significant improvement.12 Flumazenil is not used routinely as an HE therapy because of significant side effects, namely seizures, nausea, vomiting, dizziness, and agitation.

Such therapies as L-carnitine, branched amino acids (BCAA), probiotics, bromocriptine, acarbose, and zinc are among the many experimental agents currently under evaluation. Few have been tested in clinical trials.

Back to the Case

Our patient has severe HE manifested by worsening somnolence. It is postulated that ongoing alcohol abuse led to medication nonadherence, precipitating his HE, but as HE has many causes, a complete workup for infection and metabolic derangement is performed. However, it is unrevealing.

The best initial action is the prescription of lactulose, the mainstay of HE therapy. Given concern for aspiration in patients with somnolence, a feeding tube is placed for administration. The lactulose dosage will be titrated to achieve two to three soft stools per day. If the patient remains symptomatic or develops significant side effects on lactulose, the addition of an antibiotic is recommended. Neomycin, a low-cost medicine approved by the FDA for HE treatment, is a good choice. The patient will be maintained on a normal protein diet.

Bottom Line

The first-line agents used to treat episodes of acute HE are the nonabsorbable disaccharides, lactulose or lactitol. TH

Dr. Shoeb is a resident in the Department of Medicine at the University of Washington in Seattle. Dr. Best is assistant professor of medicine in the Division of General Internal Medicine at the University of Washington.

References

1. Als-Nielsen B, Gluud L, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004;2:CD003044.
2. Morgan MY, Hawley KE. Lactitol v. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind, randomized trial. Hepatology. 1987; 7(6):1278-1284.
3. Blanc P, Daurès JP, Liautard J, et al. Lactulose-neomycin combination versus placebo in the treatment of acute hepatic encephalopathy. Results of a randomized controlled trial. Gastroenterol Clin Biol. 1994;18(12):1063-1068.
4. Mas A, Rodés J, Sunyer L, et al. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. 2003;38(1):51-58.
5. Paik YH, Lee KS, Han KH, et al. Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study. Yonsei Med J. 2005;46(3):399-407.
6. Massa P, Vallerino E, Dodero M. Treatment of hepatic encephalopathy with rifaximin: double blind, double dummy study versus lactulose. Eur J Clin Res. 1993;4:7-18.
7. Williams R, James OF, Warnes TW, Morgan MY. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol. 2000;12(2):203-208.
8. Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut. 1982;23(1):1-7.
9. Córdoba J, López-Hellín J, Planas M, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41(1):38-43.
10. Poo JL, Gongora J, Sánchez-Avila F, et al. Efficacy of oral L-ornithine-L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Results of a randomized, lactulose-controlled study. Ann Hepatol. 2006;5(4):281-288.
11. Sushma S, Dasarathy S, Tandon RK, Jain S, Gupta S, Bhist MS. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. 1992;16(16):138-144.
12. Als-Nielsen B, Kjaergard LL, Gluud C. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy. Cochrane Database Syst Rev. 2001;4:CD002798.

Case

A 56-year-old man with a history of cirrhosis, complicated by esophageal varices and ongoing alcohol abuse, is admitted after his wife found him lethargic and disoriented in bed. His wife said he’d been increasingly irritable and agitated, with slurred speech, the past two days. On exam, he is somnolent but arousable; spider telangiectasias and asterixis are noted. Laboratory studies are consistent with chronic liver disease.

What is the best therapy for his acute hepatic encephalopathy?

Overview

Hepatic encephalopathy (HE) describes the spectrum of potentially reversible neuropsychiatric abnormalities seen in patients with liver dysfunction. The wide range of neuropsychiatric presentations led to the development of consensus HE classification terminology by the World Congress of Gastroenterology in 2002.

The primary tenet of all HE pathogenesis theories is firmly established: Nitrogenous substances derived from the gut adversely affect brain function. These compounds access the systemic circulation via decreased hepatic function or portal-systemic shunts. In the brain, they alter neurotransmission, which affects consciousness and behavior.

HE patients usually have advanced cirrhosis and, hence, many of the physical findings associated with severe hepatic dysfunction: muscle-wasting, jaundice, ascites, palmar erythema, edema, spider telangiectasias, and fetor hepaticus. Encephalopathy progresses from reversal of the sleep-wake cycle and mild mental status changes to irritability, confusion, and slurred speech.

Advanced neurologic features include asterixis or tongue fasciculations, bradykinesia, hyperreflexia, and ultimately coma. History and laboratory data can reveal a precipitating cause (see Table 2, p. 19). Measurement of ammonia concentration remains controversial. The value may be useful for monitoring the efficacy of ammonia-lowering therapy, but elevated levels are not required to make the diagnosis.

Multiple treatments have been used to manage HE, yet few well-designed randomized trials have assessed efficacy due to challenges inherent in measuring the wide range of neuropsychiatric presentations. Nonetheless, a critical appraisal of available data delineates a rational approach to therapy.

Review of the Data

click for large version

In addition to supportive care and the reversal of any precipitating factors, the treatment of acute HE is aimed at reducing or inhibiting intestinal ammonia production or increasing its removal (see Table 1, left).

Nonabsorbable disaccharides (NAD): Lactulose (beta-galactosidofructose) and lactitol (beta-galactosidosorbitol) are used as first-line agents for the treatment of HE and lead to symptomatic improvement in 67% to 87% of patients.1 They reduce the concentration of ammoniogenic substrates in the colonic lumen in two ways—first, by facilitating bacterial fermentation and secondary organic acid production (lowering colonic pH) and, second, by direct osmotic catharsis.

NAD are administered orally or via nasogastric tube at an initial dose of 45 ml, followed by repeated hourly doses until the patient has a bowel movement. For patients at risk of aspiration, NAD can be administered via enema (300 ml in 700 ml of water) every two hours as needed until mental function improves. Once the risk of aspiration is minimized, NAD can be administered orally and titrated to achieve two to three soft bowel movements daily (the usual oral dosage is 15 ml to 45 ml every eight to 12 hours).

Common side effects of NAD include an excessively sweet taste, flatulence, abdominal cramping, and electrolyte imbalance, particularly hypernatremia, which may further deteriorate mental status.

click for large version

Als-Nielsen et al demonstrated in a systematic review that NAD were more effective than placebo in improving HE, but NAD had no significant benefit on mortality.1 However, the effect on HE no longer reached statistical significance when the analysis was confined to studies with the highest methodological quality. In a randomized, double-blind comparison, Morgan et al showed that lactitol was more tolerable than lactulose and produced fewer side effects.2 Lactitol is not currently available for use in the U.S.

Antibiotics: Certain oral antibiotics (e.g., neomycin, rifaximin, and metronidazole) reduce urease-producing intestinal bacteria, which results in decreased ammonia production and absorption through the gastrointestinal tract. Antibiotics generally are used in patients who do not tolerate NAD or who remain symptomatic despite NAD. The combined use of NAD and antibiotics is a subject of significant clinical relevance, though data are limited.

Neomycin is approved by the FDA for treatment of acute HE. It can be administered orally at a dose of 1,000 mg every six hours for up to six days. A randomized, controlled trial of neomycin versus placebo in 39 patients with acute HE demonstrated no significant difference in time to symptom improvement.3 Another study of 80 patients receiving neomycin and lactulose demonstrated no benefit against placebo, though some data suggest that the combination of lactulose and neomycin therapy might be more effective than either agent alone against placebo.4

Rifaximin was granted an orphan drug designation by the FDA for use in HE cases and has been compared with NAD. The recommended dose is 1,200 mg three times per day. It has minimal side effects and no reported drug interactions. A study of rifaximin versus lactitol administered for five to 10 days showed approximately 80% symptomatic improvement in both groups.5 Another trial demonstrated significantly greater improvement in blood ammonia concentrations, electroencephalographic (EEG) abnormalities, and mental status with rifaximin compared with lactulose.6 Studies comparing rifaximin and lactulose, either alone or in combination, have demonstrated that rifaximin is at least similar to lactulose, and in some cases superior in reversing encephalopathy, with better tolerability reported in the antibiotic group.7

Metronidazole is not approved by the FDA for the treatment of HE but has been evaluated. The recommended oral dose of metronidazole for chronic use is 250 mg twice per day. Prolonged administration of metronidazole can be associated with gastrointestinal disturbance and neurotoxicity. In a report of 11 HE patients with mild to moderate symptoms and seven chronically affected HE cirrhotic patients treated with metronidazole for one week, Morgan and colleagues showed metronidazole to be as effective as neomycin.8

Diet: Historically, patients with HE were placed on protein-restricted diets to reduce the production of intestinal ammonia. Recent evidence suggests that excessive restriction can raise serum ammonia levels as a result of reduced muscular ammonia metabolism. Furthermore, restricting protein intake worsens nutritional status and does not improve the outcome.9

In patients with established cirrhosis, the minimal daily dietary protein intake required to maintain nitrogen balance is 0.8 g/kg to 1.0 g/kg. At this time, a normoprotein diet for HE patients is considered the standard of care.

Other agents: L-ornithine L-aspartate (LOLA), a stable salt of ornithine and aspartic acid, provides crucial substrates for glutamine and urea synthesis—key pathways in deammonation. In patients with cirrhosis and HE, oral LOLA reduces serum ammonia and improves clinical manifestations of HE, including EEG abnormalities.10 LOLA, however, is not available in the U.S.

Sodium benzoate might be beneficial in the treatment of acute HE; it increases urinary excretion of ammonia. A prospective, randomized, double-blind study of 74 patients with acute HE found that treatment with sodium benzoate 5 g twice daily, compared with lactulose, resulted in equivalent improvements in encephalopathy. There was no placebo group.11 Routine use has been limited due to concerns regarding sodium load and increased frequency of adverse gastrointestinal symptoms, particularly nausea.

Flumazenil, a short-acting benzodiazepine receptor antagonist, has been utilized on the basis of observed increases in benzodiazepine receptor activation among cirrhotic HE patients. In a systematic review of 12 controlled trials (765 patients), Als-Nielsen and colleagues found flumazenil to be associated with significant improvement.12 Flumazenil is not used routinely as an HE therapy because of significant side effects, namely seizures, nausea, vomiting, dizziness, and agitation.

Such therapies as L-carnitine, branched amino acids (BCAA), probiotics, bromocriptine, acarbose, and zinc are among the many experimental agents currently under evaluation. Few have been tested in clinical trials.

Back to the Case

Our patient has severe HE manifested by worsening somnolence. It is postulated that ongoing alcohol abuse led to medication nonadherence, precipitating his HE, but as HE has many causes, a complete workup for infection and metabolic derangement is performed. However, it is unrevealing.

The best initial action is the prescription of lactulose, the mainstay of HE therapy. Given concern for aspiration in patients with somnolence, a feeding tube is placed for administration. The lactulose dosage will be titrated to achieve two to three soft stools per day. If the patient remains symptomatic or develops significant side effects on lactulose, the addition of an antibiotic is recommended. Neomycin, a low-cost medicine approved by the FDA for HE treatment, is a good choice. The patient will be maintained on a normal protein diet.

Bottom Line

The first-line agents used to treat episodes of acute HE are the nonabsorbable disaccharides, lactulose or lactitol. TH

Dr. Shoeb is a resident in the Department of Medicine at the University of Washington in Seattle. Dr. Best is assistant professor of medicine in the Division of General Internal Medicine at the University of Washington.

References

1. Als-Nielsen B, Gluud L, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004;2:CD003044.
2. Morgan MY, Hawley KE. Lactitol v. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind, randomized trial. Hepatology. 1987; 7(6):1278-1284.
3. Blanc P, Daurès JP, Liautard J, et al. Lactulose-neomycin combination versus placebo in the treatment of acute hepatic encephalopathy. Results of a randomized controlled trial. Gastroenterol Clin Biol. 1994;18(12):1063-1068.
4. Mas A, Rodés J, Sunyer L, et al. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. 2003;38(1):51-58.
5. Paik YH, Lee KS, Han KH, et al. Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study. Yonsei Med J. 2005;46(3):399-407.
6. Massa P, Vallerino E, Dodero M. Treatment of hepatic encephalopathy with rifaximin: double blind, double dummy study versus lactulose. Eur J Clin Res. 1993;4:7-18.
7. Williams R, James OF, Warnes TW, Morgan MY. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol. 2000;12(2):203-208.
8. Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut. 1982;23(1):1-7.
9. Córdoba J, López-Hellín J, Planas M, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41(1):38-43.
10. Poo JL, Gongora J, Sánchez-Avila F, et al. Efficacy of oral L-ornithine-L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Results of a randomized, lactulose-controlled study. Ann Hepatol. 2006;5(4):281-288.
11. Sushma S, Dasarathy S, Tandon RK, Jain S, Gupta S, Bhist MS. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. 1992;16(16):138-144.
12. Als-Nielsen B, Kjaergard LL, Gluud C. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy. Cochrane Database Syst Rev. 2001;4:CD002798.

Case

A 56-year-old man with a history of cirrhosis, complicated by esophageal varices and ongoing alcohol abuse, is admitted after his wife found him lethargic and disoriented in bed. His wife said he’d been increasingly irritable and agitated, with slurred speech, the past two days. On exam, he is somnolent but arousable; spider telangiectasias and asterixis are noted. Laboratory studies are consistent with chronic liver disease.

What is the best therapy for his acute hepatic encephalopathy?

Overview

Hepatic encephalopathy (HE) describes the spectrum of potentially reversible neuropsychiatric abnormalities seen in patients with liver dysfunction. The wide range of neuropsychiatric presentations led to the development of consensus HE classification terminology by the World Congress of Gastroenterology in 2002.

The primary tenet of all HE pathogenesis theories is firmly established: Nitrogenous substances derived from the gut adversely affect brain function. These compounds access the systemic circulation via decreased hepatic function or portal-systemic shunts. In the brain, they alter neurotransmission, which affects consciousness and behavior.

HE patients usually have advanced cirrhosis and, hence, many of the physical findings associated with severe hepatic dysfunction: muscle-wasting, jaundice, ascites, palmar erythema, edema, spider telangiectasias, and fetor hepaticus. Encephalopathy progresses from reversal of the sleep-wake cycle and mild mental status changes to irritability, confusion, and slurred speech.

Advanced neurologic features include asterixis or tongue fasciculations, bradykinesia, hyperreflexia, and ultimately coma. History and laboratory data can reveal a precipitating cause (see Table 2, p. 19). Measurement of ammonia concentration remains controversial. The value may be useful for monitoring the efficacy of ammonia-lowering therapy, but elevated levels are not required to make the diagnosis.

Multiple treatments have been used to manage HE, yet few well-designed randomized trials have assessed efficacy due to challenges inherent in measuring the wide range of neuropsychiatric presentations. Nonetheless, a critical appraisal of available data delineates a rational approach to therapy.

Review of the Data

click for large version

In addition to supportive care and the reversal of any precipitating factors, the treatment of acute HE is aimed at reducing or inhibiting intestinal ammonia production or increasing its removal (see Table 1, left).

Nonabsorbable disaccharides (NAD): Lactulose (beta-galactosidofructose) and lactitol (beta-galactosidosorbitol) are used as first-line agents for the treatment of HE and lead to symptomatic improvement in 67% to 87% of patients.1 They reduce the concentration of ammoniogenic substrates in the colonic lumen in two ways—first, by facilitating bacterial fermentation and secondary organic acid production (lowering colonic pH) and, second, by direct osmotic catharsis.

NAD are administered orally or via nasogastric tube at an initial dose of 45 ml, followed by repeated hourly doses until the patient has a bowel movement. For patients at risk of aspiration, NAD can be administered via enema (300 ml in 700 ml of water) every two hours as needed until mental function improves. Once the risk of aspiration is minimized, NAD can be administered orally and titrated to achieve two to three soft bowel movements daily (the usual oral dosage is 15 ml to 45 ml every eight to 12 hours).

Common side effects of NAD include an excessively sweet taste, flatulence, abdominal cramping, and electrolyte imbalance, particularly hypernatremia, which may further deteriorate mental status.

click for large version

Als-Nielsen et al demonstrated in a systematic review that NAD were more effective than placebo in improving HE, but NAD had no significant benefit on mortality.1 However, the effect on HE no longer reached statistical significance when the analysis was confined to studies with the highest methodological quality. In a randomized, double-blind comparison, Morgan et al showed that lactitol was more tolerable than lactulose and produced fewer side effects.2 Lactitol is not currently available for use in the U.S.

Antibiotics: Certain oral antibiotics (e.g., neomycin, rifaximin, and metronidazole) reduce urease-producing intestinal bacteria, which results in decreased ammonia production and absorption through the gastrointestinal tract. Antibiotics generally are used in patients who do not tolerate NAD or who remain symptomatic despite NAD. The combined use of NAD and antibiotics is a subject of significant clinical relevance, though data are limited.

Neomycin is approved by the FDA for treatment of acute HE. It can be administered orally at a dose of 1,000 mg every six hours for up to six days. A randomized, controlled trial of neomycin versus placebo in 39 patients with acute HE demonstrated no significant difference in time to symptom improvement.3 Another study of 80 patients receiving neomycin and lactulose demonstrated no benefit against placebo, though some data suggest that the combination of lactulose and neomycin therapy might be more effective than either agent alone against placebo.4

Rifaximin was granted an orphan drug designation by the FDA for use in HE cases and has been compared with NAD. The recommended dose is 1,200 mg three times per day. It has minimal side effects and no reported drug interactions. A study of rifaximin versus lactitol administered for five to 10 days showed approximately 80% symptomatic improvement in both groups.5 Another trial demonstrated significantly greater improvement in blood ammonia concentrations, electroencephalographic (EEG) abnormalities, and mental status with rifaximin compared with lactulose.6 Studies comparing rifaximin and lactulose, either alone or in combination, have demonstrated that rifaximin is at least similar to lactulose, and in some cases superior in reversing encephalopathy, with better tolerability reported in the antibiotic group.7

Metronidazole is not approved by the FDA for the treatment of HE but has been evaluated. The recommended oral dose of metronidazole for chronic use is 250 mg twice per day. Prolonged administration of metronidazole can be associated with gastrointestinal disturbance and neurotoxicity. In a report of 11 HE patients with mild to moderate symptoms and seven chronically affected HE cirrhotic patients treated with metronidazole for one week, Morgan and colleagues showed metronidazole to be as effective as neomycin.8

Diet: Historically, patients with HE were placed on protein-restricted diets to reduce the production of intestinal ammonia. Recent evidence suggests that excessive restriction can raise serum ammonia levels as a result of reduced muscular ammonia metabolism. Furthermore, restricting protein intake worsens nutritional status and does not improve the outcome.9

In patients with established cirrhosis, the minimal daily dietary protein intake required to maintain nitrogen balance is 0.8 g/kg to 1.0 g/kg. At this time, a normoprotein diet for HE patients is considered the standard of care.

Other agents: L-ornithine L-aspartate (LOLA), a stable salt of ornithine and aspartic acid, provides crucial substrates for glutamine and urea synthesis—key pathways in deammonation. In patients with cirrhosis and HE, oral LOLA reduces serum ammonia and improves clinical manifestations of HE, including EEG abnormalities.10 LOLA, however, is not available in the U.S.

Sodium benzoate might be beneficial in the treatment of acute HE; it increases urinary excretion of ammonia. A prospective, randomized, double-blind study of 74 patients with acute HE found that treatment with sodium benzoate 5 g twice daily, compared with lactulose, resulted in equivalent improvements in encephalopathy. There was no placebo group.11 Routine use has been limited due to concerns regarding sodium load and increased frequency of adverse gastrointestinal symptoms, particularly nausea.

Flumazenil, a short-acting benzodiazepine receptor antagonist, has been utilized on the basis of observed increases in benzodiazepine receptor activation among cirrhotic HE patients. In a systematic review of 12 controlled trials (765 patients), Als-Nielsen and colleagues found flumazenil to be associated with significant improvement.12 Flumazenil is not used routinely as an HE therapy because of significant side effects, namely seizures, nausea, vomiting, dizziness, and agitation.

Such therapies as L-carnitine, branched amino acids (BCAA), probiotics, bromocriptine, acarbose, and zinc are among the many experimental agents currently under evaluation. Few have been tested in clinical trials.

Back to the Case

Our patient has severe HE manifested by worsening somnolence. It is postulated that ongoing alcohol abuse led to medication nonadherence, precipitating his HE, but as HE has many causes, a complete workup for infection and metabolic derangement is performed. However, it is unrevealing.

The best initial action is the prescription of lactulose, the mainstay of HE therapy. Given concern for aspiration in patients with somnolence, a feeding tube is placed for administration. The lactulose dosage will be titrated to achieve two to three soft stools per day. If the patient remains symptomatic or develops significant side effects on lactulose, the addition of an antibiotic is recommended. Neomycin, a low-cost medicine approved by the FDA for HE treatment, is a good choice. The patient will be maintained on a normal protein diet.

Bottom Line

The first-line agents used to treat episodes of acute HE are the nonabsorbable disaccharides, lactulose or lactitol. TH

Dr. Shoeb is a resident in the Department of Medicine at the University of Washington in Seattle. Dr. Best is assistant professor of medicine in the Division of General Internal Medicine at the University of Washington.

References

1. Als-Nielsen B, Gluud L, Gluud C. Nonabsorbable disaccharides for hepatic encephalopathy. Cochrane Database Syst Rev. 2004;2:CD003044.
2. Morgan MY, Hawley KE. Lactitol v. lactulose in the treatment of acute hepatic encephalopathy in cirrhotic patients: a double-blind, randomized trial. Hepatology. 1987; 7(6):1278-1284.
3. Blanc P, Daurès JP, Liautard J, et al. Lactulose-neomycin combination versus placebo in the treatment of acute hepatic encephalopathy. Results of a randomized controlled trial. Gastroenterol Clin Biol. 1994;18(12):1063-1068.
4. Mas A, Rodés J, Sunyer L, et al. Comparison of rifaximin and lactitol in the treatment of acute hepatic encephalopathy: results of a randomized, double-blind, double-dummy, controlled clinical trial. J Hepatol. 2003;38(1):51-58.
5. Paik YH, Lee KS, Han KH, et al. Comparison of rifaximin and lactulose for the treatment of hepatic encephalopathy: a prospective randomized study. Yonsei Med J. 2005;46(3):399-407.
6. Massa P, Vallerino E, Dodero M. Treatment of hepatic encephalopathy with rifaximin: double blind, double dummy study versus lactulose. Eur J Clin Res. 1993;4:7-18.
7. Williams R, James OF, Warnes TW, Morgan MY. Evaluation of the efficacy and safety of rifaximin in the treatment of hepatic encephalopathy: a double-blind, randomized, dose-finding multi-centre study. Eur J Gastroenterol Hepatol. 2000;12(2):203-208.
8. Morgan MH, Read AE, Speller DC. Treatment of hepatic encephalopathy with metronidazole. Gut. 1982;23(1):1-7.
9. Córdoba J, López-Hellín J, Planas M, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41(1):38-43.
10. Poo JL, Gongora J, Sánchez-Avila F, et al. Efficacy of oral L-ornithine-L-aspartate in cirrhotic patients with hyperammonemic hepatic encephalopathy. Results of a randomized, lactulose-controlled study. Ann Hepatol. 2006;5(4):281-288.
11. Sushma S, Dasarathy S, Tandon RK, Jain S, Gupta S, Bhist MS. Sodium benzoate in the treatment of acute hepatic encephalopathy: a double-blind randomized trial. Hepatology. 1992;16(16):138-144.
12. Als-Nielsen B, Kjaergard LL, Gluud C. Benzodiazepine receptor antagonists for acute and chronic hepatic encephalopathy. Cochrane Database Syst Rev. 2001;4:CD002798.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.

Pipeline Drugs

• Phentermine/topiramate (Qnexa) is an investigational drug for the treatment of obesity. This includes weight loss and weight-loss maintenance in patients who are obese or overweight with such comorbidities as hypertension, Type 2 diabetes, dyslipidemia, or central adiposity. A new drug application (NDA) was filed with the FDA for this agent late in 2009.1 Qnexa is a once-daily, oral, controlled-release formulation comprised of low-dose phentermine and topiramate, which works on both patient satiety and appetite. Clinical trials show the drug has led to significant weight loss, glycemic control, and improved cardiovascular risk factors. Common side effects in clinical trials were dry mouth, tingling, and constipation.
• Pirfenidone, a potential treatment for idiopathic pulmonary fibrosis (IPF), has been granted a priority review by the FDA.2 Idiopathic pulmonary fibrosis is a disabling and fatal disease characterized by lung inflammation and scarring. The median survival time from diagnosis is two to five years, with an approximate five-year survival rate of 20%. Patients usually are diagnosed between the ages of 20 and 70, with a median of 63 years. It affects slightly more men than women. There are no medications approved to treat this fatal disease. Pirfenidone has been shown to have both antifibrotic and anti-inflammatory properties. The most common side effects are photosensitivity rash and gastrointestinal symptoms.3 The FDA’s action date is expected to be May 4.
• FDA approval was requested for retigabine, a potential new adjunctive epilepsy treatment, on Dec. 30, 2009.4 Retigabine is a neuronal potassium channel opener for use in adults with partial-onset seizures. In Phase 3 clinical trials, common adverse effects (occurring in more than 5% of patients) were dizziness, fatigue, confused state, vertigo, tremor, abnormal coordination, diplopia, attention disturbance, asthenia, and visual blurring.

Safety Information

• Desipramine (Norpramin), a tricyclic antidepressant approved by the FDA for treating major depression in adults, has undergone a label change to reflect new safety information. The “Warnings” and “Overdosage” sections of the product label now include information stating that extreme caution needs to be used when desipramine is administered to patients with a family history of sudden death, cardiac dysrhythmias, and cardiac conduction disturbances. The information also states that seizures might precede cardiac dysrhythmias and death in some patients.5 In a related “Dear Healthcare Professional” letter, information related to this warning was included with regard to identifying patients who present with a desipramine overdose, managing gastrointestinal decontamination with activated charcoal, managing cardiovascular effects, and deletion of measuring plasma-concentration desipramine as a guide to patient monitoring.5
• Diclofenac gel (Voltaren gel), a topical NSAID indicated for the relief of osteoarthritis pain of joints amenable to topical treatment (e.g., knees and hands), has undergone a label change related to its hepatic effects section. The label has revised warnings and precautions about the potential for liver function test elevations while receiving treatment with all diclofenac-containing products.6 There have been post-marketing reports of drug-induced hepatotoxicity within the first month of treatment with this topical agent. However, this reaction can occur at any time during diclofenac treatment. Severe hepatic reactions have been reported, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure. Some of these cases resulted in fatalities or liver transplantation. Oral diclofenac also is hepatotoxic; it’s one of the most hepatotoxic NSAIDs available. To monitor patients receiving topical diclofenac, you should, after obtaining baseline transaminases, periodically measure transaminases in patients receiving long-term therapy. The optimum times for measurement are unknown. Based on available data from clinical trials and other cases, transaminases should be monitored within four to eight weeks after initiating diclofenac treatment.
• Fosamprenavir (Lexiva) has undergone a label change in the “Warnings” and “Precautions” sections, which is related to a potential association between the agent and the occurrence of myocardial infarction and dyslipidemia in adults with HIV.7 The updated label notes that patient cholesterol levels might increase if treated with fosamprenavir, and that lipid monitoring prior to and after initiating the agent should occur.
• Valproate sodium, valproic acid, and divalproex sodium have been associated with an increased risk of neural tube defects and other major birth defects (e.g., craniofacial defects and cardiovascular malformations) in babies exposed to these agents during pregnancy.8 Healthcare providers need to inform women of childbearing potential about these risks and consider alternative therapies, especially if the use of valproate is considered to treat migraines or other conditions that are not considered life-threatening. Women who are not actively planning a pregnancy and require use of valproate for medical conditions should use contraception, as birth-defect risks are high during the first trimester of pregnancy. Pregnant women using valproate should be encouraged to enroll in the North American Antiepileptic Drug Pregnancy Registry (888-233-2334 or www.aedpregnancyregistry.org). A medication guide explaining the risk and benefits of such treatment is required to be distributed with each dispensed valproate prescription.9 TH

Michele B. Kaufman, PharmD, BSc, RPh, is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

References

1. NDA submitted for Qnexa. Drugs.com Web site. Available at: http://www.drugs.com/nda/qnexa_091229.html. Accessed Jan. 7, 2010.
2. Todoruk M. InterMune’s pulmonary drug pirfenidone granted priority review by FDA. FirstWord Web site. Available at: http://www.firstwordplus.com/Fws.do?articleid=5C01296C0574469B9A67F3574353FB1E&logRowId=343385. Accessed Jan. 7, 2010.
3. FDA grants priority review of pirfenidone NDA for the treatment of patients with IPF. InterMune Web site. Available at: http://phx.corporate-ir.net/phoenix.zhtml?c=100067&p=irol-newsArticle&ID=1370133&highlight=. Accessed Jan. 7, 2010.
4. FDA accepts NDA filing for retigabine. Drugs.com Web site. Available at: http://www.drugs.com/nda/retigabine_091230.html. Accessed Jan. 7, 2010.
5. Norpramin (desipramine hydrochloride)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192655.htm. Accessed Jan. 7, 2010.
6. Voltaren gel (diclofenac sodium topical gel) 1%—hepatic effects labeling changes. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm193047.htm. Accessed Jan. 7, 2009.
7. Lexiva (fosamprenavir calcium)—Dear Healthcare Professional letter. Food and Drug Administration Web site. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192699.htm. Accessed Jan. 7, 2010.
8. FDA warns of birth defects with valproate sodium, valproic acid, and divalproex sodium. Monthly Prescribing Reference Web site. Available at: http://www.empr.com/fda-warns-of-birth-defects-with-valproate-sodium-valproic-acid-and-divalproex-sodium/article/159034/. Accessed Jan. 7, 2010.
9. Valproate sodium and related products (valproic acid and divalproex sodium): risk of birth defects. Food and Drug Administration Web site. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm192788.htm. Accessed Jan. 7, 2009.

Clinical question: What is the incidence of apnea in infants hospitalized with respiratory syncytial virus (RSV) bronchiolitis?

Background: Apnea is a known and reported complication of RSV infection in infants. In clinical practice, this relationship could be the basis for admission despite a lack of symptoms that would otherwise necessitate hospitalization. The exact nature of this association remains unclear, specifically with respect to incidence and risk factors for apnea.

Study design: Systematic chart review.

Synopsis: A literature search was conducted using a combination of the terms “apnea” (or “apnoea”), “bronchiolitis,” “respiratory syncytial virus” and/or “lower respiratory tract infection.” Studies were included if they reported apnea rates for a consecutive cohort of hospitalized infants. Thirteen studies involving 5,575 patients were reviewed.

Rates of apnea ranged from 1.2% to 23.8%. Infants of younger, postconceptional age (≤44 weeks) and pre-term infants were at greater risk for apnea. Term infants without serious underlying illness appeared to have a <1% risk of apnea, based on the most recent studies.

A consistent finding of this review was the heterogeneity of the data in the included studies. Definitions of apnea varied, were broad, and included subjective criteria. Age stratification was infrequent. Inclusion and exclusion criteria were variable with respect to age cutoffs and relevant comorbidities. Future research will need to carefully delineate all of these potential confounding variables.

Bottom line: While rates of apnea in RSV bronchiolitis are difficult to quantify, there appears to be an association with younger, postconceptional age and pre-term birth.

Citation: Ralston S, Hill V. Incidence of apnea in infants hospitalized with respiratory syncytial virus bronchiolitis: a systematic review. J Pediatr. 2009;155(5):728-733.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: What is the incidence of apnea in infants hospitalized with respiratory syncytial virus (RSV) bronchiolitis?

Background: Apnea is a known and reported complication of RSV infection in infants. In clinical practice, this relationship could be the basis for admission despite a lack of symptoms that would otherwise necessitate hospitalization. The exact nature of this association remains unclear, specifically with respect to incidence and risk factors for apnea.

Study design: Systematic chart review.

Synopsis: A literature search was conducted using a combination of the terms “apnea” (or “apnoea”), “bronchiolitis,” “respiratory syncytial virus” and/or “lower respiratory tract infection.” Studies were included if they reported apnea rates for a consecutive cohort of hospitalized infants. Thirteen studies involving 5,575 patients were reviewed.

Rates of apnea ranged from 1.2% to 23.8%. Infants of younger, postconceptional age (≤44 weeks) and pre-term infants were at greater risk for apnea. Term infants without serious underlying illness appeared to have a <1% risk of apnea, based on the most recent studies.

A consistent finding of this review was the heterogeneity of the data in the included studies. Definitions of apnea varied, were broad, and included subjective criteria. Age stratification was infrequent. Inclusion and exclusion criteria were variable with respect to age cutoffs and relevant comorbidities. Future research will need to carefully delineate all of these potential confounding variables.

Bottom line: While rates of apnea in RSV bronchiolitis are difficult to quantify, there appears to be an association with younger, postconceptional age and pre-term birth.

Citation: Ralston S, Hill V. Incidence of apnea in infants hospitalized with respiratory syncytial virus bronchiolitis: a systematic review. J Pediatr. 2009;155(5):728-733.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: What is the incidence of apnea in infants hospitalized with respiratory syncytial virus (RSV) bronchiolitis?

Background: Apnea is a known and reported complication of RSV infection in infants. In clinical practice, this relationship could be the basis for admission despite a lack of symptoms that would otherwise necessitate hospitalization. The exact nature of this association remains unclear, specifically with respect to incidence and risk factors for apnea.

Study design: Systematic chart review.

Synopsis: A literature search was conducted using a combination of the terms “apnea” (or “apnoea”), “bronchiolitis,” “respiratory syncytial virus” and/or “lower respiratory tract infection.” Studies were included if they reported apnea rates for a consecutive cohort of hospitalized infants. Thirteen studies involving 5,575 patients were reviewed.

Rates of apnea ranged from 1.2% to 23.8%. Infants of younger, postconceptional age (≤44 weeks) and pre-term infants were at greater risk for apnea. Term infants without serious underlying illness appeared to have a <1% risk of apnea, based on the most recent studies.

A consistent finding of this review was the heterogeneity of the data in the included studies. Definitions of apnea varied, were broad, and included subjective criteria. Age stratification was infrequent. Inclusion and exclusion criteria were variable with respect to age cutoffs and relevant comorbidities. Future research will need to carefully delineate all of these potential confounding variables.

Bottom line: While rates of apnea in RSV bronchiolitis are difficult to quantify, there appears to be an association with younger, postconceptional age and pre-term birth.

Citation: Ralston S, Hill V. Incidence of apnea in infants hospitalized with respiratory syncytial virus bronchiolitis: a systematic review. J Pediatr. 2009;155(5):728-733.

Reviewed by Pediatric Editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

In This Edition

Literature at a Glance

A guide to this month’s studies

• Predictors of readmission for patients with CAP.
• High-dose statins vs. lipid-lowering therapy combinations
• Catheter retention and risks of reinfection in patients with coagulase-negative staph
• Stenting vs. medical management of renal-artery stenosis
• Dabigatran for VTE
• Surgical mask vs. N95 respirator for influenza prevention
• Hospitalization and the risk of long-term cognitive decline
• Maturation of rapid-response teams and outcomes

Commonly Available Clinical Variables Predict 30-Day Readmissions for Community-Acquired Pneumonia

Clinical question: What are the risk factors for 30-day readmission in patients hospitalized for community-acquired pneumonia (CAP)?

Background: CAP is a common admission diagnosis associated with significant morbidity, mortality, and resource utilization. While prior data suggested that patients who survive a hospitalization for CAP are particularly vulnerable to readmission, few studies have examined the risk factors for readmission in this population.

Study design: Prospective, observational study.

Setting: A 400-bed teaching hospital in northern Spain.

Synopsis: From 2003 to 2005, this study consecutively enrolled 1,117 patients who were discharged after hospitalization for CAP. Eighty-one patients (7.2%) were readmitted within 30 days of discharge; 29 (35.8%) of these patients were rehospitalized for pneumonia-related causes.

Variables associated with pneumonia-related rehospitalization were treatment failure (HR 2.9; 95% CI, 1.2-6.8) and one or more instability factors at hospital discharge—for example, vital-sign abnormalities or inability to take food or medications by mouth (HR 2.8; 95% CI, 1.3-6.2). Variables associated with readmission unrelated to pneumonia were age greater than 65 years (HR 4.5; 95% CI, 1.4-14.7), Charlson comorbidity index greater than 2 (HR 1.9; 95% CI, 1.0-3.4), and decompensated comorbidities during index hospitalization.

Patients with at least two of the above risk factors were at a significantly higher risk for 30-day hospital readmission (HR 3.37; 95% CI, 2.08-5.46).

Bottom line: The risk factors for readmission after hospitalization for CAP differed between the groups with readmissions related to pneumonia versus other causes. Patients at high risk for readmission can be identified using easily available clinical variables.

Citation: Capelastegui A, España Yandiola PP, Quintana JM, et al. Predictors of short-term rehospitalization following discharge of patients hospitalized with community-acquired pneumonia. Chest. 2009;136(4): 1079-1085.

Combinations of Lipid-Lowering Agents No More Effective than High-Dose Statin Monotherapy

Clinical question: Is high-dose statin monotherapy better than combinations of lipid-lowering agents for dyslipidemia in adults at high risk for coronary artery disease?

Background: While current guidelines support the benefits of aggressive lipid targets, there is little to guide physicians as to the optimal strategy for attaining target lipid levels.

Study design: Systematic review.

Setting: North America, Europe, and Asia.

Synopsis: Very-low-strength evidence showed that statin-ezetimibe (two trials; N=439) and statin-fibrate (one trial; N=166) combinations did not reduce mortality more than high-dose statin monotherapy. No trial data were found comparing the effect of these two strategies on secondary endpoints, including myocardial infarction, stroke, or revascularization.

Two trials (N=295) suggested lower-target lipid levels were more often achieved with statin-ezetimibe combination therapy than with high-dose statin monotherapy (OR 7.21; 95% CI, 4.30-12.08).

Limitations of this systematic review include the small number of studies directly comparing the two strategies, the short duration of most of the studies included, the focus on surrogate outcomes, and the heterogeneity of the study populations’ risk for coronary artery disease. Few studies were available comparing combination therapies other than statin-ezetimibe.

Bottom line: Limited evidence suggests that the combination of a statin with another lipid-lowering agent does not improve clinical outcomes when compared with high-dose statin monotherapy. Low-quality evidence suggests that lower-target lipid levels were more often reached with statin-ezetimibe combination therapy than with high-dose statin monotherapy.

Citation: Sharma M, Ansari MT, Abou-Setta AM, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med. 2009;151(9):622-630.

Catheter Retention in Catheter-Related Coagulase-Negative Staphylococcal Bacteremia Is a Significant Risk Factor for Recurrent Infection

Clinical question: Should central venous catheters (CVC) be removed in patients with coagulase-negative staphylococcal catheter-related bloodstream infections (CRBSI)?

Background: Current guidelines for the management of coagulase-negative staphylococcal CRBSI do not recommend routine removal of the CVC, but are based on studies that did not use a strict definition of coagulase-negative staphylococcal CRBSI. Additionally, the studies did not look explicitly at the risk of recurrent infection.

Study design: Retrospective chart review.

Setting: Single academic medical center.

Synopsis: The study retrospectively evaluated 188 patients with coagulase-negative staphylococcal CRBSI. Immediate resolution of the infection was not influenced by the management of the CVC (retention vs. removal or exchange). However, using the multiple logistic regression technique, patients with catheter retention were found to be 6.6 times (95% CI, 1.8-23.9 times) more likely to have recurrence compared with those patients whose catheter was removed or exchanged.

Bottom line: While CVC management does not appear to have an impact on the acute resolution of infection, catheter retention is a significant risk factor for recurrent bacteremia.

Citation: Raad I, Kassar R, Ghannam D, Chaftari AM, Hachem R, Jiang Y. Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain? Clin Infect Dis. 2009;49(8):1187-1194.

Revascularization Offers No Benefit over Medical Therapy for Renal-Artery Stenosis

Clinical question: Does revascularization plus medical therapy compared with medical therapy alone improve outcomes in patients with renal-artery stenosis?

Background: Renal-artery stenosis is associated with significant hypertension and renal dysfunction. Revascularization for atherosclerotic renal-artery stenosis can improve artery patency, but it remains unclear if it provides clinical benefit in terms of preserving renal function or reducing overall mortality.

Study design: Randomized, controlled trial.

Setting: Fifty-seven outpatient sites in the United Kingdom, Australia, and New Zealand.

Synopsis: The study randomized 806 patients with renal-artery stenosis to receive either medical therapy alone (N=403) or medical management plus endovascular revascularization (N=403).

The majority of the patients who underwent revascularization (95%) received a stent.

The data show no significant difference between the two groups in the rate of progression of renal dysfunction, systolic blood pressure, rates of adverse renal and cardiovascular events, and overall survival. Of the 359 patients who underwent revascularization, 23 (6%) experienced serious complications from the procedure, including two deaths and three cases of amputated toes or limbs.

The primary limitation of this trial is the population studied. The trial only included subjects for whom revascularization offered uncertain clinical benefits, according to their doctor. Those subjects for whom revascularization offered certain clinical benefits, as noted by their primary-care physician (PCP), were excluded from the study. Examples include patients presenting with rapidly progressive renal dysfunction or pulmonary edema thought to be a result of renal-artery stenosis.

Bottom line: Revascularization provides no benefit to most patients with renal-artery stenosis, and is associated with some risk.

Citation: ASTRAL investigators, Wheatley K, Ives N, et al. Revascularization versus medical therapy for renal-artery stenosis. N Eng J Med. 2009;361(20):1953-1962.

Dabigatran as Effective as Warfarin in Treatment of Acute VTE

Clinical question: Is dabigatran a safe and effective alternative to warfarin for treatment of acute VTE?

Background: Parenteral anticoagulation followed by warfarin is the standard of care for acute VTE. Warfarin requires frequent monitoring and has numerous drug and food interactions. Dabigatran, which the FDA has yet to approve for use in the U.S., is an oral direct thrombin inhibitor that does not require laboratory monitoring. The role of dabigatran in acute VTE has not been evaluated.

Study design: Randomized, double-blind, noninferiority trial.

Setting: Two hundred twenty-two clinical centers in 29 countries.

Synopsis: This study randomized 2,564 patients with documented VTE (either DVT or pulmonary embolism [PE]) to receive dabigatran 150mg twice daily or warfarin after at least five days of a parenteral anticoagulant. Warfarin was dose-adjusted to an INR goal of 2.0-3.0. The primary outcome was incidence of recurrent VTE and related deaths at six months.

A total of 2.4% of patients assigned to dabigatran and 2.1% of patients assigned to warfarin had recurrent VTE (HR 1.10; 95% CI, 0.8-1.5), which met criteria for noninferiority. Major bleeding occurred in 1.6% of patients assigned to dabigatran and 1.9% assigned to warfarin (HR 0.82; 95% CI, 0.45-1.48). There was no difference between groups in overall adverse effects. Discontinuation due to adverse events was 9% with dabigatran compared with 6.8% with warfarin (P=0.05). Dyspepsia was more common with dabigatran (P<0.001).

Bottom line: Following parenteral anticoagulation, dabigatran is a safe and effective alternative to warfarin for the treatment of acute VTE and does not require therapeutic monitoring.

Citation: Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-2352.

Surgical Masks as Effective as N95 Respirators for Preventing Influenza

Clinical question: How effective are surgical masks compared with N95 respirators in protecting healthcare workers against influenza?

Background: Evidence surrounding the effectiveness of the surgical mask compared with the N95 respirator for protecting healthcare workers against influenza is sparse.

Study design: Randomized, controlled trial.

Setting: Eight hospitals in Ontario.

Synopsis: The study looked at 446 nurses working in EDs, medical units, and pediatric units randomized to use either a fit-tested N95 respirator or a surgical mask when caring for patients with febrile respiratory illness during the 2008-2009 flu season. The primary outcome measured was laboratory-confirmed influenza. Only a minority of the study participants (30% in the surgical mask group; 28% in the respirator group) received the influenza vaccine during the study year.

Influenza infection occurred with similar incidence in both the surgical-mask and N95 respirator groups (23.6% vs. 22.9%). A two-week audit period demonstrated solid adherence to the assigned respiratory protection device in both groups (11 out of 11 nurses were compliant in the surgical-mask group; six out of seven nurses were compliant in the respirator group).

The major limitation of this study is that it cannot be extrapolated to other settings where there is a high risk for aerosolization, such as intubation or bronchoscopy, where N95 respirators may be more effective than surgical masks.

Bottom line: Surgical masks are as effective as fit-tested N95 respirators in protecting healthcare workers against influenza in most settings.

Citation: Loeb M, Dafoe N, Mahony J, et al. Surgical mask vs. N95 respirator for preventing influenza among health care workers: a randomized trial. JAMA. 2009;302 (17):1865-1871.

Neither Major Illness Nor Noncardiac Surgery Associated with Long-Term Cognitive Decline in Older Patients

Clinical question: Is there a measurable and lasting cognitive decline in older adults following noncardiac surgery or major illness?

Background: Despite limited evidence, there is some concern that elderly patients are susceptible to significant, long-term deterioration in mental function following surgery or a major illness. Prior studies often have been limited by lack of information about the trajectory of surgical patients’ cognitive status before surgery and lack of relevant control groups.

Study design: Retrospective, cohort study.

Setting: Single outpatient research center.

Synopsis: The Alzheimer’s Disease Research Center (ADRC) at the University of Washington in St. Louis continually enrolls research subjects without regard to their baseline cognitive function and provides annual assessment of cognitive functioning.

From the ADRC database, 575 eligible research participants were identified. Of these, 361 had very mild or mild dementia at enrollment, and 214 had no dementia. Participants were then categorized into three groups: those who had undergone noncardiac surgery (N=180); those who had been admitted to the hospital with a major illness (N=119); and those who had experienced neither surgery nor major illness (N=276).

Cognitive trajectory did not differ between the three groups, although participants with baseline dementia declined more rapidly than participants without dementia. Although 23% of patients without dementia developed detectable evidence of dementia during the study period, this outcome was not more common following surgery or major illness.

As participants were assessed annually, this study does not address the issue of post-operative delirium or early cognitive impairment following surgery.

Bottom line: There is no evidence for a long-term effect on cognitive function independently attributable to noncardiac surgery or major illness.

Citation: Avidan MS, Searleman AC, Storandt M, et al. Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology. 2009;111(5):964-970.

Rapid-Response System Maturation Decreases Delays in Emergency Team Activation

Clinical question: Does the maturation of a rapid-response system (RRS) improve performance by decreasing delays in medical emergency team (MET) activation?

Background: RRSs have been widely embraced as a possible means to reduce inpatient cardiopulmonary arrests and unplanned ICU admissions. Assessment of RRSs early in their implementation might underestimate their long-term efficacy. Whether the use and performance of RRSs improve as they mature is currently unknown.

Study design: Observational, cohort study.

Setting: Single tertiary-care hospital.

Synopsis: A recent cohort of 200 patients receiving MET review was prospectively compared with a control cohort of 400 patients receiving an MET review five years earlier, at the start of RRS implementation. Information obtained on the two cohorts included demographics, timing of MET activation in relation to the first documented MET review criterion (activation delay), and patient outcomes.

Fewer patients in the recent cohort had delayed MET activation (22.0% vs. 40.3%). The recent cohort also was independently associated with a decreased risk of delayed activation (OR 0.45; 95% C.I., 0.30-0.67) and ICU admission (OR 0.5; 95% C.I., 0.32-0.78). Delayed MET activation independently was associated with greater risk of unplanned ICU admission (OR 1.79; 95% C.I., 1.33-2.93) and hospital mortality (OR 2.18; 95% C.I., 1.42-3.33).

The study is limited by its observational nature, and thus the association between greater delay and unfavorable outcomes should not infer causality.

Bottom line: The maturation of a RRS decreases delays in MET activation. RRSs might need to mature before their full impact is felt.

Citation: Calzavacca P, Licari E, Tee A, et al. The impact of Rapid Response System on delayed emergency team activation patient characteristics and outcomes—a follow-up study. Resuscitation. 2010;81(1):31-35. TH

In This Edition

Literature at a Glance

A guide to this month’s studies

• Predictors of readmission for patients with CAP.
• High-dose statins vs. lipid-lowering therapy combinations
• Catheter retention and risks of reinfection in patients with coagulase-negative staph
• Stenting vs. medical management of renal-artery stenosis
• Dabigatran for VTE
• Surgical mask vs. N95 respirator for influenza prevention
• Hospitalization and the risk of long-term cognitive decline
• Maturation of rapid-response teams and outcomes

Commonly Available Clinical Variables Predict 30-Day Readmissions for Community-Acquired Pneumonia

Clinical question: What are the risk factors for 30-day readmission in patients hospitalized for community-acquired pneumonia (CAP)?

Background: CAP is a common admission diagnosis associated with significant morbidity, mortality, and resource utilization. While prior data suggested that patients who survive a hospitalization for CAP are particularly vulnerable to readmission, few studies have examined the risk factors for readmission in this population.

Study design: Prospective, observational study.

Setting: A 400-bed teaching hospital in northern Spain.

Synopsis: From 2003 to 2005, this study consecutively enrolled 1,117 patients who were discharged after hospitalization for CAP. Eighty-one patients (7.2%) were readmitted within 30 days of discharge; 29 (35.8%) of these patients were rehospitalized for pneumonia-related causes.

Variables associated with pneumonia-related rehospitalization were treatment failure (HR 2.9; 95% CI, 1.2-6.8) and one or more instability factors at hospital discharge—for example, vital-sign abnormalities or inability to take food or medications by mouth (HR 2.8; 95% CI, 1.3-6.2). Variables associated with readmission unrelated to pneumonia were age greater than 65 years (HR 4.5; 95% CI, 1.4-14.7), Charlson comorbidity index greater than 2 (HR 1.9; 95% CI, 1.0-3.4), and decompensated comorbidities during index hospitalization.

Patients with at least two of the above risk factors were at a significantly higher risk for 30-day hospital readmission (HR 3.37; 95% CI, 2.08-5.46).

Bottom line: The risk factors for readmission after hospitalization for CAP differed between the groups with readmissions related to pneumonia versus other causes. Patients at high risk for readmission can be identified using easily available clinical variables.

Citation: Capelastegui A, España Yandiola PP, Quintana JM, et al. Predictors of short-term rehospitalization following discharge of patients hospitalized with community-acquired pneumonia. Chest. 2009;136(4): 1079-1085.

Combinations of Lipid-Lowering Agents No More Effective than High-Dose Statin Monotherapy

Clinical question: Is high-dose statin monotherapy better than combinations of lipid-lowering agents for dyslipidemia in adults at high risk for coronary artery disease?

Background: While current guidelines support the benefits of aggressive lipid targets, there is little to guide physicians as to the optimal strategy for attaining target lipid levels.

Study design: Systematic review.

Setting: North America, Europe, and Asia.

Synopsis: Very-low-strength evidence showed that statin-ezetimibe (two trials; N=439) and statin-fibrate (one trial; N=166) combinations did not reduce mortality more than high-dose statin monotherapy. No trial data were found comparing the effect of these two strategies on secondary endpoints, including myocardial infarction, stroke, or revascularization.

Two trials (N=295) suggested lower-target lipid levels were more often achieved with statin-ezetimibe combination therapy than with high-dose statin monotherapy (OR 7.21; 95% CI, 4.30-12.08).

Limitations of this systematic review include the small number of studies directly comparing the two strategies, the short duration of most of the studies included, the focus on surrogate outcomes, and the heterogeneity of the study populations’ risk for coronary artery disease. Few studies were available comparing combination therapies other than statin-ezetimibe.

Bottom line: Limited evidence suggests that the combination of a statin with another lipid-lowering agent does not improve clinical outcomes when compared with high-dose statin monotherapy. Low-quality evidence suggests that lower-target lipid levels were more often reached with statin-ezetimibe combination therapy than with high-dose statin monotherapy.

Citation: Sharma M, Ansari MT, Abou-Setta AM, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med. 2009;151(9):622-630.

Catheter Retention in Catheter-Related Coagulase-Negative Staphylococcal Bacteremia Is a Significant Risk Factor for Recurrent Infection

Clinical question: Should central venous catheters (CVC) be removed in patients with coagulase-negative staphylococcal catheter-related bloodstream infections (CRBSI)?

Background: Current guidelines for the management of coagulase-negative staphylococcal CRBSI do not recommend routine removal of the CVC, but are based on studies that did not use a strict definition of coagulase-negative staphylococcal CRBSI. Additionally, the studies did not look explicitly at the risk of recurrent infection.

Study design: Retrospective chart review.

Setting: Single academic medical center.

Synopsis: The study retrospectively evaluated 188 patients with coagulase-negative staphylococcal CRBSI. Immediate resolution of the infection was not influenced by the management of the CVC (retention vs. removal or exchange). However, using the multiple logistic regression technique, patients with catheter retention were found to be 6.6 times (95% CI, 1.8-23.9 times) more likely to have recurrence compared with those patients whose catheter was removed or exchanged.

Bottom line: While CVC management does not appear to have an impact on the acute resolution of infection, catheter retention is a significant risk factor for recurrent bacteremia.

Citation: Raad I, Kassar R, Ghannam D, Chaftari AM, Hachem R, Jiang Y. Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain? Clin Infect Dis. 2009;49(8):1187-1194.

Revascularization Offers No Benefit over Medical Therapy for Renal-Artery Stenosis

Clinical question: Does revascularization plus medical therapy compared with medical therapy alone improve outcomes in patients with renal-artery stenosis?

Background: Renal-artery stenosis is associated with significant hypertension and renal dysfunction. Revascularization for atherosclerotic renal-artery stenosis can improve artery patency, but it remains unclear if it provides clinical benefit in terms of preserving renal function or reducing overall mortality.

Study design: Randomized, controlled trial.

Setting: Fifty-seven outpatient sites in the United Kingdom, Australia, and New Zealand.

Synopsis: The study randomized 806 patients with renal-artery stenosis to receive either medical therapy alone (N=403) or medical management plus endovascular revascularization (N=403).

The majority of the patients who underwent revascularization (95%) received a stent.

The data show no significant difference between the two groups in the rate of progression of renal dysfunction, systolic blood pressure, rates of adverse renal and cardiovascular events, and overall survival. Of the 359 patients who underwent revascularization, 23 (6%) experienced serious complications from the procedure, including two deaths and three cases of amputated toes or limbs.

The primary limitation of this trial is the population studied. The trial only included subjects for whom revascularization offered uncertain clinical benefits, according to their doctor. Those subjects for whom revascularization offered certain clinical benefits, as noted by their primary-care physician (PCP), were excluded from the study. Examples include patients presenting with rapidly progressive renal dysfunction or pulmonary edema thought to be a result of renal-artery stenosis.

Bottom line: Revascularization provides no benefit to most patients with renal-artery stenosis, and is associated with some risk.

Citation: ASTRAL investigators, Wheatley K, Ives N, et al. Revascularization versus medical therapy for renal-artery stenosis. N Eng J Med. 2009;361(20):1953-1962.

Dabigatran as Effective as Warfarin in Treatment of Acute VTE

Clinical question: Is dabigatran a safe and effective alternative to warfarin for treatment of acute VTE?

Background: Parenteral anticoagulation followed by warfarin is the standard of care for acute VTE. Warfarin requires frequent monitoring and has numerous drug and food interactions. Dabigatran, which the FDA has yet to approve for use in the U.S., is an oral direct thrombin inhibitor that does not require laboratory monitoring. The role of dabigatran in acute VTE has not been evaluated.

Study design: Randomized, double-blind, noninferiority trial.

Setting: Two hundred twenty-two clinical centers in 29 countries.

Synopsis: This study randomized 2,564 patients with documented VTE (either DVT or pulmonary embolism [PE]) to receive dabigatran 150mg twice daily or warfarin after at least five days of a parenteral anticoagulant. Warfarin was dose-adjusted to an INR goal of 2.0-3.0. The primary outcome was incidence of recurrent VTE and related deaths at six months.

A total of 2.4% of patients assigned to dabigatran and 2.1% of patients assigned to warfarin had recurrent VTE (HR 1.10; 95% CI, 0.8-1.5), which met criteria for noninferiority. Major bleeding occurred in 1.6% of patients assigned to dabigatran and 1.9% assigned to warfarin (HR 0.82; 95% CI, 0.45-1.48). There was no difference between groups in overall adverse effects. Discontinuation due to adverse events was 9% with dabigatran compared with 6.8% with warfarin (P=0.05). Dyspepsia was more common with dabigatran (P<0.001).

Bottom line: Following parenteral anticoagulation, dabigatran is a safe and effective alternative to warfarin for the treatment of acute VTE and does not require therapeutic monitoring.

Citation: Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-2352.

Surgical Masks as Effective as N95 Respirators for Preventing Influenza

Clinical question: How effective are surgical masks compared with N95 respirators in protecting healthcare workers against influenza?

Background: Evidence surrounding the effectiveness of the surgical mask compared with the N95 respirator for protecting healthcare workers against influenza is sparse.

Study design: Randomized, controlled trial.

Setting: Eight hospitals in Ontario.

Synopsis: The study looked at 446 nurses working in EDs, medical units, and pediatric units randomized to use either a fit-tested N95 respirator or a surgical mask when caring for patients with febrile respiratory illness during the 2008-2009 flu season. The primary outcome measured was laboratory-confirmed influenza. Only a minority of the study participants (30% in the surgical mask group; 28% in the respirator group) received the influenza vaccine during the study year.

Influenza infection occurred with similar incidence in both the surgical-mask and N95 respirator groups (23.6% vs. 22.9%). A two-week audit period demonstrated solid adherence to the assigned respiratory protection device in both groups (11 out of 11 nurses were compliant in the surgical-mask group; six out of seven nurses were compliant in the respirator group).

The major limitation of this study is that it cannot be extrapolated to other settings where there is a high risk for aerosolization, such as intubation or bronchoscopy, where N95 respirators may be more effective than surgical masks.

Bottom line: Surgical masks are as effective as fit-tested N95 respirators in protecting healthcare workers against influenza in most settings.

Citation: Loeb M, Dafoe N, Mahony J, et al. Surgical mask vs. N95 respirator for preventing influenza among health care workers: a randomized trial. JAMA. 2009;302 (17):1865-1871.

Neither Major Illness Nor Noncardiac Surgery Associated with Long-Term Cognitive Decline in Older Patients

Clinical question: Is there a measurable and lasting cognitive decline in older adults following noncardiac surgery or major illness?

Background: Despite limited evidence, there is some concern that elderly patients are susceptible to significant, long-term deterioration in mental function following surgery or a major illness. Prior studies often have been limited by lack of information about the trajectory of surgical patients’ cognitive status before surgery and lack of relevant control groups.

Study design: Retrospective, cohort study.

Setting: Single outpatient research center.

Synopsis: The Alzheimer’s Disease Research Center (ADRC) at the University of Washington in St. Louis continually enrolls research subjects without regard to their baseline cognitive function and provides annual assessment of cognitive functioning.

From the ADRC database, 575 eligible research participants were identified. Of these, 361 had very mild or mild dementia at enrollment, and 214 had no dementia. Participants were then categorized into three groups: those who had undergone noncardiac surgery (N=180); those who had been admitted to the hospital with a major illness (N=119); and those who had experienced neither surgery nor major illness (N=276).

Cognitive trajectory did not differ between the three groups, although participants with baseline dementia declined more rapidly than participants without dementia. Although 23% of patients without dementia developed detectable evidence of dementia during the study period, this outcome was not more common following surgery or major illness.

As participants were assessed annually, this study does not address the issue of post-operative delirium or early cognitive impairment following surgery.

Bottom line: There is no evidence for a long-term effect on cognitive function independently attributable to noncardiac surgery or major illness.

Citation: Avidan MS, Searleman AC, Storandt M, et al. Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology. 2009;111(5):964-970.

Rapid-Response System Maturation Decreases Delays in Emergency Team Activation

Clinical question: Does the maturation of a rapid-response system (RRS) improve performance by decreasing delays in medical emergency team (MET) activation?

Background: RRSs have been widely embraced as a possible means to reduce inpatient cardiopulmonary arrests and unplanned ICU admissions. Assessment of RRSs early in their implementation might underestimate their long-term efficacy. Whether the use and performance of RRSs improve as they mature is currently unknown.

Study design: Observational, cohort study.

Setting: Single tertiary-care hospital.

Synopsis: A recent cohort of 200 patients receiving MET review was prospectively compared with a control cohort of 400 patients receiving an MET review five years earlier, at the start of RRS implementation. Information obtained on the two cohorts included demographics, timing of MET activation in relation to the first documented MET review criterion (activation delay), and patient outcomes.

Fewer patients in the recent cohort had delayed MET activation (22.0% vs. 40.3%). The recent cohort also was independently associated with a decreased risk of delayed activation (OR 0.45; 95% C.I., 0.30-0.67) and ICU admission (OR 0.5; 95% C.I., 0.32-0.78). Delayed MET activation independently was associated with greater risk of unplanned ICU admission (OR 1.79; 95% C.I., 1.33-2.93) and hospital mortality (OR 2.18; 95% C.I., 1.42-3.33).

The study is limited by its observational nature, and thus the association between greater delay and unfavorable outcomes should not infer causality.

Bottom line: The maturation of a RRS decreases delays in MET activation. RRSs might need to mature before their full impact is felt.

Citation: Calzavacca P, Licari E, Tee A, et al. The impact of Rapid Response System on delayed emergency team activation patient characteristics and outcomes—a follow-up study. Resuscitation. 2010;81(1):31-35. TH

In This Edition

Literature at a Glance

A guide to this month’s studies

• Predictors of readmission for patients with CAP.
• High-dose statins vs. lipid-lowering therapy combinations
• Catheter retention and risks of reinfection in patients with coagulase-negative staph
• Stenting vs. medical management of renal-artery stenosis
• Dabigatran for VTE
• Surgical mask vs. N95 respirator for influenza prevention
• Hospitalization and the risk of long-term cognitive decline
• Maturation of rapid-response teams and outcomes

Commonly Available Clinical Variables Predict 30-Day Readmissions for Community-Acquired Pneumonia

Clinical question: What are the risk factors for 30-day readmission in patients hospitalized for community-acquired pneumonia (CAP)?

Background: CAP is a common admission diagnosis associated with significant morbidity, mortality, and resource utilization. While prior data suggested that patients who survive a hospitalization for CAP are particularly vulnerable to readmission, few studies have examined the risk factors for readmission in this population.

Study design: Prospective, observational study.

Setting: A 400-bed teaching hospital in northern Spain.

Synopsis: From 2003 to 2005, this study consecutively enrolled 1,117 patients who were discharged after hospitalization for CAP. Eighty-one patients (7.2%) were readmitted within 30 days of discharge; 29 (35.8%) of these patients were rehospitalized for pneumonia-related causes.

Variables associated with pneumonia-related rehospitalization were treatment failure (HR 2.9; 95% CI, 1.2-6.8) and one or more instability factors at hospital discharge—for example, vital-sign abnormalities or inability to take food or medications by mouth (HR 2.8; 95% CI, 1.3-6.2). Variables associated with readmission unrelated to pneumonia were age greater than 65 years (HR 4.5; 95% CI, 1.4-14.7), Charlson comorbidity index greater than 2 (HR 1.9; 95% CI, 1.0-3.4), and decompensated comorbidities during index hospitalization.

Patients with at least two of the above risk factors were at a significantly higher risk for 30-day hospital readmission (HR 3.37; 95% CI, 2.08-5.46).

Bottom line: The risk factors for readmission after hospitalization for CAP differed between the groups with readmissions related to pneumonia versus other causes. Patients at high risk for readmission can be identified using easily available clinical variables.

Citation: Capelastegui A, España Yandiola PP, Quintana JM, et al. Predictors of short-term rehospitalization following discharge of patients hospitalized with community-acquired pneumonia. Chest. 2009;136(4): 1079-1085.

Combinations of Lipid-Lowering Agents No More Effective than High-Dose Statin Monotherapy

Clinical question: Is high-dose statin monotherapy better than combinations of lipid-lowering agents for dyslipidemia in adults at high risk for coronary artery disease?

Background: While current guidelines support the benefits of aggressive lipid targets, there is little to guide physicians as to the optimal strategy for attaining target lipid levels.

Study design: Systematic review.

Setting: North America, Europe, and Asia.

Synopsis: Very-low-strength evidence showed that statin-ezetimibe (two trials; N=439) and statin-fibrate (one trial; N=166) combinations did not reduce mortality more than high-dose statin monotherapy. No trial data were found comparing the effect of these two strategies on secondary endpoints, including myocardial infarction, stroke, or revascularization.

Two trials (N=295) suggested lower-target lipid levels were more often achieved with statin-ezetimibe combination therapy than with high-dose statin monotherapy (OR 7.21; 95% CI, 4.30-12.08).

Limitations of this systematic review include the small number of studies directly comparing the two strategies, the short duration of most of the studies included, the focus on surrogate outcomes, and the heterogeneity of the study populations’ risk for coronary artery disease. Few studies were available comparing combination therapies other than statin-ezetimibe.

Bottom line: Limited evidence suggests that the combination of a statin with another lipid-lowering agent does not improve clinical outcomes when compared with high-dose statin monotherapy. Low-quality evidence suggests that lower-target lipid levels were more often reached with statin-ezetimibe combination therapy than with high-dose statin monotherapy.

Citation: Sharma M, Ansari MT, Abou-Setta AM, et al. Systematic review: comparative effectiveness and harms of combination therapy and monotherapy for dyslipidemia. Ann Intern Med. 2009;151(9):622-630.

Catheter Retention in Catheter-Related Coagulase-Negative Staphylococcal Bacteremia Is a Significant Risk Factor for Recurrent Infection

Clinical question: Should central venous catheters (CVC) be removed in patients with coagulase-negative staphylococcal catheter-related bloodstream infections (CRBSI)?

Background: Current guidelines for the management of coagulase-negative staphylococcal CRBSI do not recommend routine removal of the CVC, but are based on studies that did not use a strict definition of coagulase-negative staphylococcal CRBSI. Additionally, the studies did not look explicitly at the risk of recurrent infection.

Study design: Retrospective chart review.

Setting: Single academic medical center.

Synopsis: The study retrospectively evaluated 188 patients with coagulase-negative staphylococcal CRBSI. Immediate resolution of the infection was not influenced by the management of the CVC (retention vs. removal or exchange). However, using the multiple logistic regression technique, patients with catheter retention were found to be 6.6 times (95% CI, 1.8-23.9 times) more likely to have recurrence compared with those patients whose catheter was removed or exchanged.

Bottom line: While CVC management does not appear to have an impact on the acute resolution of infection, catheter retention is a significant risk factor for recurrent bacteremia.

Citation: Raad I, Kassar R, Ghannam D, Chaftari AM, Hachem R, Jiang Y. Management of the catheter in documented catheter-related coagulase-negative staphylococcal bacteremia: remove or retain? Clin Infect Dis. 2009;49(8):1187-1194.

Revascularization Offers No Benefit over Medical Therapy for Renal-Artery Stenosis

Clinical question: Does revascularization plus medical therapy compared with medical therapy alone improve outcomes in patients with renal-artery stenosis?

Background: Renal-artery stenosis is associated with significant hypertension and renal dysfunction. Revascularization for atherosclerotic renal-artery stenosis can improve artery patency, but it remains unclear if it provides clinical benefit in terms of preserving renal function or reducing overall mortality.

Study design: Randomized, controlled trial.

Setting: Fifty-seven outpatient sites in the United Kingdom, Australia, and New Zealand.

Synopsis: The study randomized 806 patients with renal-artery stenosis to receive either medical therapy alone (N=403) or medical management plus endovascular revascularization (N=403).

The majority of the patients who underwent revascularization (95%) received a stent.

The data show no significant difference between the two groups in the rate of progression of renal dysfunction, systolic blood pressure, rates of adverse renal and cardiovascular events, and overall survival. Of the 359 patients who underwent revascularization, 23 (6%) experienced serious complications from the procedure, including two deaths and three cases of amputated toes or limbs.

The primary limitation of this trial is the population studied. The trial only included subjects for whom revascularization offered uncertain clinical benefits, according to their doctor. Those subjects for whom revascularization offered certain clinical benefits, as noted by their primary-care physician (PCP), were excluded from the study. Examples include patients presenting with rapidly progressive renal dysfunction or pulmonary edema thought to be a result of renal-artery stenosis.

Bottom line: Revascularization provides no benefit to most patients with renal-artery stenosis, and is associated with some risk.

Citation: ASTRAL investigators, Wheatley K, Ives N, et al. Revascularization versus medical therapy for renal-artery stenosis. N Eng J Med. 2009;361(20):1953-1962.

Dabigatran as Effective as Warfarin in Treatment of Acute VTE

Clinical question: Is dabigatran a safe and effective alternative to warfarin for treatment of acute VTE?

Background: Parenteral anticoagulation followed by warfarin is the standard of care for acute VTE. Warfarin requires frequent monitoring and has numerous drug and food interactions. Dabigatran, which the FDA has yet to approve for use in the U.S., is an oral direct thrombin inhibitor that does not require laboratory monitoring. The role of dabigatran in acute VTE has not been evaluated.

Study design: Randomized, double-blind, noninferiority trial.

Setting: Two hundred twenty-two clinical centers in 29 countries.

Synopsis: This study randomized 2,564 patients with documented VTE (either DVT or pulmonary embolism [PE]) to receive dabigatran 150mg twice daily or warfarin after at least five days of a parenteral anticoagulant. Warfarin was dose-adjusted to an INR goal of 2.0-3.0. The primary outcome was incidence of recurrent VTE and related deaths at six months.

A total of 2.4% of patients assigned to dabigatran and 2.1% of patients assigned to warfarin had recurrent VTE (HR 1.10; 95% CI, 0.8-1.5), which met criteria for noninferiority. Major bleeding occurred in 1.6% of patients assigned to dabigatran and 1.9% assigned to warfarin (HR 0.82; 95% CI, 0.45-1.48). There was no difference between groups in overall adverse effects. Discontinuation due to adverse events was 9% with dabigatran compared with 6.8% with warfarin (P=0.05). Dyspepsia was more common with dabigatran (P<0.001).

Bottom line: Following parenteral anticoagulation, dabigatran is a safe and effective alternative to warfarin for the treatment of acute VTE and does not require therapeutic monitoring.

Citation: Schulman S, Kearon C, Kakkar AK, et al. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med. 2009;361(24):2342-2352.

Surgical Masks as Effective as N95 Respirators for Preventing Influenza

Clinical question: How effective are surgical masks compared with N95 respirators in protecting healthcare workers against influenza?

Background: Evidence surrounding the effectiveness of the surgical mask compared with the N95 respirator for protecting healthcare workers against influenza is sparse.

Study design: Randomized, controlled trial.

Setting: Eight hospitals in Ontario.

Synopsis: The study looked at 446 nurses working in EDs, medical units, and pediatric units randomized to use either a fit-tested N95 respirator or a surgical mask when caring for patients with febrile respiratory illness during the 2008-2009 flu season. The primary outcome measured was laboratory-confirmed influenza. Only a minority of the study participants (30% in the surgical mask group; 28% in the respirator group) received the influenza vaccine during the study year.

Influenza infection occurred with similar incidence in both the surgical-mask and N95 respirator groups (23.6% vs. 22.9%). A two-week audit period demonstrated solid adherence to the assigned respiratory protection device in both groups (11 out of 11 nurses were compliant in the surgical-mask group; six out of seven nurses were compliant in the respirator group).

The major limitation of this study is that it cannot be extrapolated to other settings where there is a high risk for aerosolization, such as intubation or bronchoscopy, where N95 respirators may be more effective than surgical masks.

Bottom line: Surgical masks are as effective as fit-tested N95 respirators in protecting healthcare workers against influenza in most settings.

Citation: Loeb M, Dafoe N, Mahony J, et al. Surgical mask vs. N95 respirator for preventing influenza among health care workers: a randomized trial. JAMA. 2009;302 (17):1865-1871.

Neither Major Illness Nor Noncardiac Surgery Associated with Long-Term Cognitive Decline in Older Patients

Clinical question: Is there a measurable and lasting cognitive decline in older adults following noncardiac surgery or major illness?

Background: Despite limited evidence, there is some concern that elderly patients are susceptible to significant, long-term deterioration in mental function following surgery or a major illness. Prior studies often have been limited by lack of information about the trajectory of surgical patients’ cognitive status before surgery and lack of relevant control groups.

Study design: Retrospective, cohort study.

Setting: Single outpatient research center.

Synopsis: The Alzheimer’s Disease Research Center (ADRC) at the University of Washington in St. Louis continually enrolls research subjects without regard to their baseline cognitive function and provides annual assessment of cognitive functioning.

From the ADRC database, 575 eligible research participants were identified. Of these, 361 had very mild or mild dementia at enrollment, and 214 had no dementia. Participants were then categorized into three groups: those who had undergone noncardiac surgery (N=180); those who had been admitted to the hospital with a major illness (N=119); and those who had experienced neither surgery nor major illness (N=276).

Cognitive trajectory did not differ between the three groups, although participants with baseline dementia declined more rapidly than participants without dementia. Although 23% of patients without dementia developed detectable evidence of dementia during the study period, this outcome was not more common following surgery or major illness.

As participants were assessed annually, this study does not address the issue of post-operative delirium or early cognitive impairment following surgery.

Bottom line: There is no evidence for a long-term effect on cognitive function independently attributable to noncardiac surgery or major illness.

Citation: Avidan MS, Searleman AC, Storandt M, et al. Long-term cognitive decline in older subjects was not attributable to noncardiac surgery or major illness. Anesthesiology. 2009;111(5):964-970.

Rapid-Response System Maturation Decreases Delays in Emergency Team Activation

Clinical question: Does the maturation of a rapid-response system (RRS) improve performance by decreasing delays in medical emergency team (MET) activation?

Background: RRSs have been widely embraced as a possible means to reduce inpatient cardiopulmonary arrests and unplanned ICU admissions. Assessment of RRSs early in their implementation might underestimate their long-term efficacy. Whether the use and performance of RRSs improve as they mature is currently unknown.

Study design: Observational, cohort study.

Setting: Single tertiary-care hospital.

Synopsis: A recent cohort of 200 patients receiving MET review was prospectively compared with a control cohort of 400 patients receiving an MET review five years earlier, at the start of RRS implementation. Information obtained on the two cohorts included demographics, timing of MET activation in relation to the first documented MET review criterion (activation delay), and patient outcomes.

Fewer patients in the recent cohort had delayed MET activation (22.0% vs. 40.3%). The recent cohort also was independently associated with a decreased risk of delayed activation (OR 0.45; 95% C.I., 0.30-0.67) and ICU admission (OR 0.5; 95% C.I., 0.32-0.78). Delayed MET activation independently was associated with greater risk of unplanned ICU admission (OR 1.79; 95% C.I., 1.33-2.93) and hospital mortality (OR 2.18; 95% C.I., 1.42-3.33).

The study is limited by its observational nature, and thus the association between greater delay and unfavorable outcomes should not infer causality.

Bottom line: The maturation of a RRS decreases delays in MET activation. RRSs might need to mature before their full impact is felt.

Citation: Calzavacca P, Licari E, Tee A, et al. The impact of Rapid Response System on delayed emergency team activation patient characteristics and outcomes—a follow-up study. Resuscitation. 2010;81(1):31-35. TH