The National Institute for Health and Clinical Excellence says that it will recommend rituximab in combination with several chemotherapy regimens as first-line treatments for people with advanced follicular lymphoma.

Current NICE guidance recommends rituximab in combination with cyclophosphamide, vincristine and prednisolone (CVP) for this patient group.

In final draft guidance issued Dec. 1, the agency, which makes cost- and clinical-effectiveness decisions for England and Wales, said that rituximab (MabThera, Roche) could also be used in combination with chlorambucil or the following chemotherapy regimens:

– Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).

– Mitoxantrone, chlorambucil, and prednisolone (MCP).

– Cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon-alpha (CHVPi).

All recommended regimens are authorized in Europe, are commonly used in the United Kingdom, and have been evaluated with and without rituximab in open-label clinical trials in patients with stage III and IV follicular lymphoma. For all, addition of rituximab was shown to correspond with a significant survival benefit compared with the chemotherapy-alone groups.

Having a range of chemotherapy options available is important, NICE said, due to differences in patients’ fitness as they age. Chlorambucil is seen as an option mainly for older patients, or patients with a lower performance status.

Rituximab is a genetically engineered chimeric monoclonal antibody that targets cells bearing the CD20 surface marker. For follicular lymphoma, dosage is 375 mg/m² body surface area for up to eight cycles, administered on day 1 of the chemotherapy cycle. Each 10-mL (100-mg) vial costs £174.63, or £873.15 for 500 mL.

Current NICE guidance also recommends rituximab monotherapy as a maintenance treatment immediately following first-line treatment with rituximab-containing chemotherapy regimens. While most patients presenting with advanced follicular lymphoma are treatment-naive, rituximab plus chemotherapy is also recommended by NICE for relapsed or refractory advanced follicular lymphoma.

The NICE reviewers found all of the rituximab-plus-chemotherapy regimens to be well within NICE’s cost-effectiveness parameters, with an estimated incremental cost effectiveness ratio of £7,720 per quality-adjusted life year for rituximab plus CVP; £10,800 per QALY gained for rituximab plus CHOP; and £9,320 per QALY gained for rituximab plus MCP. For CHVPi, the cost-effectiveness estimates remained uncertain. However, the agency felt it was unlikely that estimates would exceed its "threshold range" of between £20,000 and £30,000 per QALY.

The National Institute for Health and Clinical Excellence says that it will recommend rituximab in combination with several chemotherapy regimens as first-line treatments for people with advanced follicular lymphoma.

Current NICE guidance recommends rituximab in combination with cyclophosphamide, vincristine and prednisolone (CVP) for this patient group.

In final draft guidance issued Dec. 1, the agency, which makes cost- and clinical-effectiveness decisions for England and Wales, said that rituximab (MabThera, Roche) could also be used in combination with chlorambucil or the following chemotherapy regimens:

– Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).

– Mitoxantrone, chlorambucil, and prednisolone (MCP).

– Cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon-alpha (CHVPi).

All recommended regimens are authorized in Europe, are commonly used in the United Kingdom, and have been evaluated with and without rituximab in open-label clinical trials in patients with stage III and IV follicular lymphoma. For all, addition of rituximab was shown to correspond with a significant survival benefit compared with the chemotherapy-alone groups.

Having a range of chemotherapy options available is important, NICE said, due to differences in patients’ fitness as they age. Chlorambucil is seen as an option mainly for older patients, or patients with a lower performance status.

Rituximab is a genetically engineered chimeric monoclonal antibody that targets cells bearing the CD20 surface marker. For follicular lymphoma, dosage is 375 mg/m² body surface area for up to eight cycles, administered on day 1 of the chemotherapy cycle. Each 10-mL (100-mg) vial costs £174.63, or £873.15 for 500 mL.

Current NICE guidance also recommends rituximab monotherapy as a maintenance treatment immediately following first-line treatment with rituximab-containing chemotherapy regimens. While most patients presenting with advanced follicular lymphoma are treatment-naive, rituximab plus chemotherapy is also recommended by NICE for relapsed or refractory advanced follicular lymphoma.

The NICE reviewers found all of the rituximab-plus-chemotherapy regimens to be well within NICE’s cost-effectiveness parameters, with an estimated incremental cost effectiveness ratio of £7,720 per quality-adjusted life year for rituximab plus CVP; £10,800 per QALY gained for rituximab plus CHOP; and £9,320 per QALY gained for rituximab plus MCP. For CHVPi, the cost-effectiveness estimates remained uncertain. However, the agency felt it was unlikely that estimates would exceed its "threshold range" of between £20,000 and £30,000 per QALY.

The National Institute for Health and Clinical Excellence says that it will recommend rituximab in combination with several chemotherapy regimens as first-line treatments for people with advanced follicular lymphoma.

Current NICE guidance recommends rituximab in combination with cyclophosphamide, vincristine and prednisolone (CVP) for this patient group.

In final draft guidance issued Dec. 1, the agency, which makes cost- and clinical-effectiveness decisions for England and Wales, said that rituximab (MabThera, Roche) could also be used in combination with chlorambucil or the following chemotherapy regimens:

– Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).

– Mitoxantrone, chlorambucil, and prednisolone (MCP).

– Cyclophosphamide, doxorubicin, etoposide, prednisolone, and interferon-alpha (CHVPi).

All recommended regimens are authorized in Europe, are commonly used in the United Kingdom, and have been evaluated with and without rituximab in open-label clinical trials in patients with stage III and IV follicular lymphoma. For all, addition of rituximab was shown to correspond with a significant survival benefit compared with the chemotherapy-alone groups.

Having a range of chemotherapy options available is important, NICE said, due to differences in patients’ fitness as they age. Chlorambucil is seen as an option mainly for older patients, or patients with a lower performance status.

Rituximab is a genetically engineered chimeric monoclonal antibody that targets cells bearing the CD20 surface marker. For follicular lymphoma, dosage is 375 mg/m² body surface area for up to eight cycles, administered on day 1 of the chemotherapy cycle. Each 10-mL (100-mg) vial costs £174.63, or £873.15 for 500 mL.

Current NICE guidance also recommends rituximab monotherapy as a maintenance treatment immediately following first-line treatment with rituximab-containing chemotherapy regimens. While most patients presenting with advanced follicular lymphoma are treatment-naive, rituximab plus chemotherapy is also recommended by NICE for relapsed or refractory advanced follicular lymphoma.

The NICE reviewers found all of the rituximab-plus-chemotherapy regimens to be well within NICE’s cost-effectiveness parameters, with an estimated incremental cost effectiveness ratio of £7,720 per quality-adjusted life year for rituximab plus CVP; £10,800 per QALY gained for rituximab plus CHOP; and £9,320 per QALY gained for rituximab plus MCP. For CHVPi, the cost-effectiveness estimates remained uncertain. However, the agency felt it was unlikely that estimates would exceed its "threshold range" of between £20,000 and £30,000 per QALY.

ORLANDO – A fifth of women with an acute myocardial infarction have previously undiagnosed diabetes, according to results from a German registry that included 706 women.

The registry analysis also showed that prevalence of previously undiagnosed diabetes in women with a recent MI significantly exceeded the rate in men, Dr. Anselm K. Gitt said at the annual scientific sessions of the American Heart Association. And the 3-year outcome of women with an acute MI and newly diagnosed diabetes closely tracked the outcomes of women who survived an acute MI and had previously diagnosed diabetes. The 3-year mortality rate in both groups of women was about 30%, reported Dr. Gitt, a cardiologist at the Heart Center in Ludwigshafen, Germany, and vice director of the Myocardial Infarction Research Institute in Ludwigshafen.

Guidelines issued in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes recommended that physicians routinely perform an oral glucose tolerance test on patients following a MI who had not previously been diagnosed with diabetes (Eur. Heart J. 2007;28:88-136). "We started this study to see whether the recommendation had value in clinical practice. I think our new data confirm the recommendation," Dr. Gitt said.

However, because of results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, simply focusing on intensive glycemic control in post-MI patients with newly diagnosed diabetes is probably not an ideal management approach, he acknowledged. Although study results have not clearly established an optimal strategy, he suggested "good glycemic control with attention to avoiding hypoglycemia, along with aggressively treating cardiovascular risk factors such as lipids and hypertension."

Dr. Gitt and his associates tallied the prevalence of diabetes in acute MI patients with data collected in the SWEETHEART registry, which enrolled 2,767 patients within 24 hours of either an ST-elevation MI or non ST-elevation MI at 30 German centers, and then followed the patients for 3 years. The group included 706 women (26%), with an average age of 71 years, compared with an average age of 64 among the 2,061 enrolled men. The prevalence of previously diagnosed diabetes was 30% among the women, and 23% among the men.

All patients without a prior diagnosis of diabetes underwent assessment with an oral glucose tolerance test, following the recommendation made by the ESC and EASD in 2007. This identified an additional 20% of the women and 15% of the men with diabetes (a blood glucose level greater than 200 mg/dL 2 hours following the oral glucose challenge), as well as 18% of the women and 23% of the men with impaired glucose tolerance. The total 50% prevalence of both newly and previously diagnosed diabetes among the women who entered the study was significantly higher than the combined 38% prevalence rate among the men, Dr. Gitt said.

During hospitalization for the index acute MI, the mortality rate among both the women and men newly diagnosed with diabetes was about 3%, similar to the rate among those with previously diagnosed diabetes. Mortality among the women and men with newly identified impaired glucose tolerance ran 0.8% and 0.4%, respectively, while mortality among those with no diabetes or glucose impairment was 1.2% among women and 1.3% among men.

During the 3-year follow-up, mortality in the newly diagnosed women was 31%, and it was 22% among the men. This finding is "important," because it shows that once physicians diagnose diabetes in a recent MI patient "their risk is very high," Dr. Gitt said. In women with a prior diabetes diagnosis the 3-year mortality rate was 30%, while in men with previously identified diabetes the mortality rate was 35%. Men and women with either impaired glucose tolerance or no identified glucose metabolism disorder had substantially lower 3-year mortality rates than ranged from 11% to 13%.

Dr. Gitt has received research grants from, and has been a consultant to or served on the speakers bureau for, AstraZeneca, Bristol Myers Squibb, Essex, GlaxoSmithKline, Merck, MSD, Pfizer, Roche, Eli Lilly, Sanofi-Aventis, Schering Plough, and Servier. He said that he has received research grants from Abbott and Hexal, and that he has been a consultant to or served on a speakers bureau for Amgen, Daiichi Sankyo, Iroko, and Novo Nordisk.

ORLANDO – A fifth of women with an acute myocardial infarction have previously undiagnosed diabetes, according to results from a German registry that included 706 women.

The registry analysis also showed that prevalence of previously undiagnosed diabetes in women with a recent MI significantly exceeded the rate in men, Dr. Anselm K. Gitt said at the annual scientific sessions of the American Heart Association. And the 3-year outcome of women with an acute MI and newly diagnosed diabetes closely tracked the outcomes of women who survived an acute MI and had previously diagnosed diabetes. The 3-year mortality rate in both groups of women was about 30%, reported Dr. Gitt, a cardiologist at the Heart Center in Ludwigshafen, Germany, and vice director of the Myocardial Infarction Research Institute in Ludwigshafen.

Guidelines issued in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes recommended that physicians routinely perform an oral glucose tolerance test on patients following a MI who had not previously been diagnosed with diabetes (Eur. Heart J. 2007;28:88-136). "We started this study to see whether the recommendation had value in clinical practice. I think our new data confirm the recommendation," Dr. Gitt said.

However, because of results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, simply focusing on intensive glycemic control in post-MI patients with newly diagnosed diabetes is probably not an ideal management approach, he acknowledged. Although study results have not clearly established an optimal strategy, he suggested "good glycemic control with attention to avoiding hypoglycemia, along with aggressively treating cardiovascular risk factors such as lipids and hypertension."

Dr. Gitt and his associates tallied the prevalence of diabetes in acute MI patients with data collected in the SWEETHEART registry, which enrolled 2,767 patients within 24 hours of either an ST-elevation MI or non ST-elevation MI at 30 German centers, and then followed the patients for 3 years. The group included 706 women (26%), with an average age of 71 years, compared with an average age of 64 among the 2,061 enrolled men. The prevalence of previously diagnosed diabetes was 30% among the women, and 23% among the men.

All patients without a prior diagnosis of diabetes underwent assessment with an oral glucose tolerance test, following the recommendation made by the ESC and EASD in 2007. This identified an additional 20% of the women and 15% of the men with diabetes (a blood glucose level greater than 200 mg/dL 2 hours following the oral glucose challenge), as well as 18% of the women and 23% of the men with impaired glucose tolerance. The total 50% prevalence of both newly and previously diagnosed diabetes among the women who entered the study was significantly higher than the combined 38% prevalence rate among the men, Dr. Gitt said.

During hospitalization for the index acute MI, the mortality rate among both the women and men newly diagnosed with diabetes was about 3%, similar to the rate among those with previously diagnosed diabetes. Mortality among the women and men with newly identified impaired glucose tolerance ran 0.8% and 0.4%, respectively, while mortality among those with no diabetes or glucose impairment was 1.2% among women and 1.3% among men.

During the 3-year follow-up, mortality in the newly diagnosed women was 31%, and it was 22% among the men. This finding is "important," because it shows that once physicians diagnose diabetes in a recent MI patient "their risk is very high," Dr. Gitt said. In women with a prior diabetes diagnosis the 3-year mortality rate was 30%, while in men with previously identified diabetes the mortality rate was 35%. Men and women with either impaired glucose tolerance or no identified glucose metabolism disorder had substantially lower 3-year mortality rates than ranged from 11% to 13%.

Dr. Gitt has received research grants from, and has been a consultant to or served on the speakers bureau for, AstraZeneca, Bristol Myers Squibb, Essex, GlaxoSmithKline, Merck, MSD, Pfizer, Roche, Eli Lilly, Sanofi-Aventis, Schering Plough, and Servier. He said that he has received research grants from Abbott and Hexal, and that he has been a consultant to or served on a speakers bureau for Amgen, Daiichi Sankyo, Iroko, and Novo Nordisk.

ORLANDO – A fifth of women with an acute myocardial infarction have previously undiagnosed diabetes, according to results from a German registry that included 706 women.

The registry analysis also showed that prevalence of previously undiagnosed diabetes in women with a recent MI significantly exceeded the rate in men, Dr. Anselm K. Gitt said at the annual scientific sessions of the American Heart Association. And the 3-year outcome of women with an acute MI and newly diagnosed diabetes closely tracked the outcomes of women who survived an acute MI and had previously diagnosed diabetes. The 3-year mortality rate in both groups of women was about 30%, reported Dr. Gitt, a cardiologist at the Heart Center in Ludwigshafen, Germany, and vice director of the Myocardial Infarction Research Institute in Ludwigshafen.

Guidelines issued in 2007 by the European Society of Cardiology and the European Association for the Study of Diabetes recommended that physicians routinely perform an oral glucose tolerance test on patients following a MI who had not previously been diagnosed with diabetes (Eur. Heart J. 2007;28:88-136). "We started this study to see whether the recommendation had value in clinical practice. I think our new data confirm the recommendation," Dr. Gitt said.

However, because of results from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial and the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial, simply focusing on intensive glycemic control in post-MI patients with newly diagnosed diabetes is probably not an ideal management approach, he acknowledged. Although study results have not clearly established an optimal strategy, he suggested "good glycemic control with attention to avoiding hypoglycemia, along with aggressively treating cardiovascular risk factors such as lipids and hypertension."

Dr. Gitt and his associates tallied the prevalence of diabetes in acute MI patients with data collected in the SWEETHEART registry, which enrolled 2,767 patients within 24 hours of either an ST-elevation MI or non ST-elevation MI at 30 German centers, and then followed the patients for 3 years. The group included 706 women (26%), with an average age of 71 years, compared with an average age of 64 among the 2,061 enrolled men. The prevalence of previously diagnosed diabetes was 30% among the women, and 23% among the men.

All patients without a prior diagnosis of diabetes underwent assessment with an oral glucose tolerance test, following the recommendation made by the ESC and EASD in 2007. This identified an additional 20% of the women and 15% of the men with diabetes (a blood glucose level greater than 200 mg/dL 2 hours following the oral glucose challenge), as well as 18% of the women and 23% of the men with impaired glucose tolerance. The total 50% prevalence of both newly and previously diagnosed diabetes among the women who entered the study was significantly higher than the combined 38% prevalence rate among the men, Dr. Gitt said.

During hospitalization for the index acute MI, the mortality rate among both the women and men newly diagnosed with diabetes was about 3%, similar to the rate among those with previously diagnosed diabetes. Mortality among the women and men with newly identified impaired glucose tolerance ran 0.8% and 0.4%, respectively, while mortality among those with no diabetes or glucose impairment was 1.2% among women and 1.3% among men.

During the 3-year follow-up, mortality in the newly diagnosed women was 31%, and it was 22% among the men. This finding is "important," because it shows that once physicians diagnose diabetes in a recent MI patient "their risk is very high," Dr. Gitt said. In women with a prior diabetes diagnosis the 3-year mortality rate was 30%, while in men with previously identified diabetes the mortality rate was 35%. Men and women with either impaired glucose tolerance or no identified glucose metabolism disorder had substantially lower 3-year mortality rates than ranged from 11% to 13%.

Dr. Gitt has received research grants from, and has been a consultant to or served on the speakers bureau for, AstraZeneca, Bristol Myers Squibb, Essex, GlaxoSmithKline, Merck, MSD, Pfizer, Roche, Eli Lilly, Sanofi-Aventis, Schering Plough, and Servier. He said that he has received research grants from Abbott and Hexal, and that he has been a consultant to or served on a speakers bureau for Amgen, Daiichi Sankyo, Iroko, and Novo Nordisk.

To the Editor: The article “Dabigatran: Will it change clinical practice”¹ has a dangerous error. In its Key Points, it says “dabigatran is a potent, reversible direct thrombin inhibitor.” In fact, it is not reversible.²

Shamefully poor editing.

To the Editor: The article “Dabigatran: Will it change clinical practice”¹ has a dangerous error. In its Key Points, it says “dabigatran is a potent, reversible direct thrombin inhibitor.” In fact, it is not reversible.²

Shamefully poor editing.

To the Editor: The article “Dabigatran: Will it change clinical practice”¹ has a dangerous error. In its Key Points, it says “dabigatran is a potent, reversible direct thrombin inhibitor.” In fact, it is not reversible.²

Shamefully poor editing.

In Reply: This is not an error. When we¹ and others² said that dabigatran is a reversible direct thrombin inhibitor, we were referring to its effect at the molecular level, the appropriate description of its mechanism of action. However, we suspect that Dr. Smith means that there is no antidote to give in cases of bleeding or overdose. We share his concern and we discussed this in our article.

Unlike heparin, direct thrombin inhibitors act independently of antithrombin and inhibit thrombin bound to fibrin or fibrin degradation products. There are two types of direct thrombin inhibitors: bivalent (eg, hirudin) and univalent (eg, argatroban, ximelagatran, and dabigatran). The bivalent ones block thrombin at its active site and at an exosite and form an irreversible complex with it. The univalent ones interact with only the active site and reversibly inhibit thrombin, eventually dissociating from it and leaving a small amount of free, enzymatically active thrombin available for hemostatic interactions. Therefore, in contrast to the hirudins, they produce relatively transient thrombin inhibition.^2–4

As we pointed out in our article, the lack of an antidote for dabigatran and the lack of experience in treating bleeding complications are major concerns. Fortunately, the drug has a short half-life (12–14 hours) so that the treatment is to withhold the next dose while maintaining adequate diuresis and giving transfusions as indicated. Activated charcoal, given orally to reduce absorption, is under evaluation but must be given within 1 or 2 hours after the dabigatran dose.¹ Dabigatran can be removed by dialysis (in part because it is a reversible inhibitor), a measure that may be necessary in life-threatening cases. Recombinant activated factor VII or prothrombin complex concentrates may be additional treatment options.^1,4 With time will come experience and, we hope, evidence-based guidelines.

In Reply: This is not an error. When we¹ and others² said that dabigatran is a reversible direct thrombin inhibitor, we were referring to its effect at the molecular level, the appropriate description of its mechanism of action. However, we suspect that Dr. Smith means that there is no antidote to give in cases of bleeding or overdose. We share his concern and we discussed this in our article.

Unlike heparin, direct thrombin inhibitors act independently of antithrombin and inhibit thrombin bound to fibrin or fibrin degradation products. There are two types of direct thrombin inhibitors: bivalent (eg, hirudin) and univalent (eg, argatroban, ximelagatran, and dabigatran). The bivalent ones block thrombin at its active site and at an exosite and form an irreversible complex with it. The univalent ones interact with only the active site and reversibly inhibit thrombin, eventually dissociating from it and leaving a small amount of free, enzymatically active thrombin available for hemostatic interactions. Therefore, in contrast to the hirudins, they produce relatively transient thrombin inhibition.^2–4

As we pointed out in our article, the lack of an antidote for dabigatran and the lack of experience in treating bleeding complications are major concerns. Fortunately, the drug has a short half-life (12–14 hours) so that the treatment is to withhold the next dose while maintaining adequate diuresis and giving transfusions as indicated. Activated charcoal, given orally to reduce absorption, is under evaluation but must be given within 1 or 2 hours after the dabigatran dose.¹ Dabigatran can be removed by dialysis (in part because it is a reversible inhibitor), a measure that may be necessary in life-threatening cases. Recombinant activated factor VII or prothrombin complex concentrates may be additional treatment options.^1,4 With time will come experience and, we hope, evidence-based guidelines.

In Reply: This is not an error. When we¹ and others² said that dabigatran is a reversible direct thrombin inhibitor, we were referring to its effect at the molecular level, the appropriate description of its mechanism of action. However, we suspect that Dr. Smith means that there is no antidote to give in cases of bleeding or overdose. We share his concern and we discussed this in our article.

Unlike heparin, direct thrombin inhibitors act independently of antithrombin and inhibit thrombin bound to fibrin or fibrin degradation products. There are two types of direct thrombin inhibitors: bivalent (eg, hirudin) and univalent (eg, argatroban, ximelagatran, and dabigatran). The bivalent ones block thrombin at its active site and at an exosite and form an irreversible complex with it. The univalent ones interact with only the active site and reversibly inhibit thrombin, eventually dissociating from it and leaving a small amount of free, enzymatically active thrombin available for hemostatic interactions. Therefore, in contrast to the hirudins, they produce relatively transient thrombin inhibition.^2–4

As we pointed out in our article, the lack of an antidote for dabigatran and the lack of experience in treating bleeding complications are major concerns. Fortunately, the drug has a short half-life (12–14 hours) so that the treatment is to withhold the next dose while maintaining adequate diuresis and giving transfusions as indicated. Activated charcoal, given orally to reduce absorption, is under evaluation but must be given within 1 or 2 hours after the dabigatran dose.¹ Dabigatran can be removed by dialysis (in part because it is a reversible inhibitor), a measure that may be necessary in life-threatening cases. Recombinant activated factor VII or prothrombin complex concentrates may be additional treatment options.^1,4 With time will come experience and, we hope, evidence-based guidelines.

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At 480-bed Emory University Hospital Midtown in Atlanta, the physicians and staff seemingly are doing all the right things to foil one of hospital’s archenemies: Clostridium difficile. The bacteria, better known as C. diff, is responsible for a sharp rise in hospital-acquired infections over the past decade, rivaling even MRSA.

In 2010, Emory Midtown launched a campaign to boost awareness of the importance of hand washing before and after treating patients infected with C. diff and those likely to be infected. They also began using the polymerase-chain-reaction-based assay to detect the bacteria, a test with much higher sensitivity that helps to more efficiently identify those infected so control measures can be more prompt and targeted. They use a hypochlorite mixture to clean the rooms of those infected, which is considered a must. And a committee monitors the use of antibiotics to prevent overuse—often the scapegoat for the rise of the hard-to-kill bacteria.

Still, at Emory, the rate of C. diff is about the same as the national average, says hospitalist Ketino Kobaidze, MD, assistant professor at the Emory University School of Medicine and a member of the antimicrobial stewardship and infectious disease control committees at Midtown. While Dr. Kobaidze says her institution is doing a good job of trying to keep C. diff under control, she thinks hospitalists can do more.

“My feeling is that we are not as involved as we’re supposed to be,” she says. “I think we need to be a little bit more proactive, be involved in committees and research activities across the hospital.”

You Are Not Alone

The experience at Emory Midtown is far from unusual—healthcare facilities, and hospitalists, across the country have seen healthcare-related C. diff cases more than double since 2001 to between 400,000 and 500,000 a year, says Carolyn Gould, MD, a medical epidemiologist in the division of healthcare quality promotion at the Centers for Disease Control and Prevention (CDC) in Atlanta.

Hospitalists, whether they realize it or not, are intimately involved in how well the C. diff outbreak is controlled. Infectious-disease (ID) specialists say hospitalists are perfectly situated to make an impact in efforts to help curb the outbreak.

“Hospitalists are critical to this effort,” Dr. Gould says. “They’re in the hospital day in and day out, and they’re constantly interacting with the patients, staff, and administration. They’re often the first on the scene to see a patient who might have suddenly developed diarrhea; they’re the first to react. I think they’re in a prime position to play a leadership role to prevent C. diff infections.”

They’re also situated well to work with infection-control experts on antimicrobial stewardship programs, she says.

“I look at hospitalists just like I would have looked at internists managing their own patients 15 years ago,” says Stuart Cohen, MD, an ID expert with the University of California at Davis and a fellow with the Infectious Diseases Society of America who was lead author of the latest published IDSA guidelines on C. diff treatment. “And so they’re the first-line people.”

continued below...

Mayo Shows How a Simple Step Can Make Big Difference in C. Diff

Listen to Dr. Gould

Sometimes even when it comes to a huge problem like widespread bacterial infections, simplicity is best.

The Mayo Clinic, in a project to cut the rate of C. diff infections, asked its workers to do one extra thing: Wipe down high-touch areas with bleach wipes. The effort worked; infections were all but eradicated in units that had been having five to seven infections per month.

The results of the project, recently published in Infectious Control and Hospital Epidemiology, show the importance of simple steps as long as they’re carried out regularly and thoroughly.¹

The project began when Robert Orenstein, DO, associate professor of medicine in infectious diseases who then worked in Rochester, Minn., established a surveillance network for C. diff infections at Mayo Clinic at the time when such infections were being noted more widely throughout the U.S. and Canada. The network began tracking the cases and found that one inpatient medical unit primarily composed of patients with gastrointestinal diseases had a C. diff rate 10 times higher than the rest of the hospital. Surveillance also showed that universally gloved hematology and oncology units had substantially lower rates of C. diff infection despite high-risk patients.

Dr. Orenstein knew he had to make a change in the GI unit, but it wasn’t feasible to institute universal gloving, so he turned to bleach wipes.

Dr. Orenstein

Twice a day, housekeeping staff wiped down all “high-touch” areas (light switches, toilet handles, bed rails) in all of the rooms. The wipes contain 0.55% sodium hypochlorite. Within six months, the number of C. diff cases fell to almost zero.

“We were just in shock,” Dr. Orenstein says. He attributed the improvement to a reduction in the “colonization pressure”—if a high concentration of patients with C. diff can cause abundant transmissions quickly, the opposite is also true.

The greatly improved figures were shared with housekeeping, which initially complained about the smell but were encouraged to keep doors open and rooms ventilated. The bleach wipes, which Dr. Orenstein acknowledges mean an additional expense, leave a white residue when dry, so the surfaces are wiped down with water after the recommended contact time.

Dr. Orenstein notes that the results came even without a change in hand hygiene, which he had deemed not feasible because of the hospital’s lack of sinks. He isn’t diminishing the importance of hand washing, but the project does show how effective a single step can be.

The key, Dr. Orenstein adds, might be that it was just one change involving just one group of staff. “Why we think it was so effective is it was really one group that had to change their behavior and we worked with them, educated them,” he says.

He emphasizes that the wipes don’t come at the expense of other measures, like thorough cleaning of all rooms and antibiotic stewardship programs.

“You do all of those and do them well,” he says, “then you get the reduction of C. diff in the hospital.”

A Tough Bug

Believed to be aided largely by the use of broad-spectrum antibiotics that knock out the colon’s natural flora, C. diff in the hospital—as well as nursing homes and acute-care facilities—has raged for much of the past decade. Its rise is tied to the emergence of a new hypervirulent strain known as BI/NAP1/027, or NAP1 for short. The strain is highly resistant to fluoroquinolones, such as ciprofloxacin and levofloxacin, which are used often in healthcare settings.

“A fluoroquinolone will wipe out a lot of your normal flora in your gut,” Dr. Gould says. “But it won’t wipe out C. diff, in particular this hypervirulent strain. And so this strain can flourish in the presence of fluoroquinolones.” The strain produces up to 15 to 20 times more toxins than other C. diff strains, according to some data, she adds.

Vancomycin (Vanconin) and metronidazole (Flagyl) are the most common antibiotics used to treat patients infected with C. diff. Mortality rates are higher among the elderly, largely because of their weaker immune system, Dr. Gould says. Studies have generally shown mortality rates of 10% or a bit lower.¹

More recent studies have shown that the number of hospital-related C. diff cases might have begun to level off in 2008 and 2009. Dr. Gould says she thinks the leveling off is for real, but there is debate over what the immediate future holds.

“There’s a lot of work and initiatives, especially state-based initiatives, that are being done in hospitals. And there’s reason to believe they’re effective,” she says, adding it’s harder to get a good picture of the problem in long-term care facilities and in the community.

Dr. Cohen with the IDSA says it’s too soon to say whether the problem is hitting a plateau. “CDC data are always a couple of years behind,” he says. “Until you see another data point, you can’t tell whether that’s just a transient flattening and whether it’s going to keep going up or not.”

Kevin Kavanagh, MD, founder of the patient advocacy group Health Watch USA and a retired otolaryngologist in Kentucky who has taken a keen interest in the C. diff problem, says he doesn’t think the end of the tunnel is within view yet.

“I think C. diff is going to get worse before it gets better,” Dr. Kavanagh says. “And that’s not necessarily because the healthcare profession isn’t doing due diligence. This is a tough organism.—it can be tough to treat and can be very tough to kill.”

The Best Defense?

Because C. diff lives within protective spores, sound hand hygiene practices and room-cleaning practices are essential for keeping infections to a minimum. Alcohol-based hand sanitizers, effective against other organisms including MRSA, do not kill C. diff. The bacteria must be mechanically removed through hand washing.

And even hand washing might not be totally effective at getting rid of the spores, which means it’s important for healthcare workers to gown and glove in high-risk rooms.

Sodium hypochlorite solutions, or bleach mixtures, have to be used to clean rooms occupied by patients with C. diff, and the prevailing thought is to clean the rooms of patients suspected of having C. diff, even if those cases might not be confirmed.

Equally important to cleaning and hand washing is systemwide emphasis on antibiotic stewardship. A 2011 study at the State University of New York Buffalo found that the risk of a C. diff infection rose with the number of antibiotics taken.²

If someone is very sick and you’re not sure what is going on, it’s very reasonable to treat them empirically with broad-spectrum antibiotics. The important thing is that you send the appropriate cultures before so that you know what you’re treating and you can optimize those antibiotics with daily assessments.

—Carolyn Gould, MD, medical epidemiologist, division of healthcare quality promotion, Centers of Disease Control and Prevention, Atlanta

While a broad-spectrum antibiotic might be necessary at first, once the results of cultures are received, the treatment should be finely tailored to kill only the problem bacteria so that the body’s natural defenses aren’t broken down, Dr. Gould explains.

“If someone is very sick and you’re not sure what is going on, it’s very reasonable to treat them empirically with broad-spectrum antibiotics,” she says. “The important thing is that you send the appropriate cultures before so that you know what you’re treating and you can optimize those antibiotics with daily assessments.”

Dr. Cohen

It’s clear why an overreliance on broad-spectrum drugs prevails in U.S. health settings, Dr. Cohen acknowledges. Recent literature suggests treating critically ill patients with wide-ranging antimicrobials as the mortality rate can be twice as high with narrower options. “I think people have gotten very quick to give broad-spectrum therapy,” he says.

continued below...

Knocking Out Clostridium Difficile

Listen to Dr. Gould

Here are the guidelines on treatment of C. diff infections (CDI) as recommended by the Infectious Diseases Society of America:

First steps:

• Discontinue therapy with the inciting antimicrobial agent(s) as soon as possible as this may influence the risk of CDI recurrence.
• When severe or complicated CDI is suspected, initiate empirical treatment as soon as the diagnosis is suspected.
• If the stool toxin assay result is negative, the decision to initiate, stop, or continue treatment must be individualized.
• If possible, avoid use of antiperistaltic agents as they may obscure symptoms and precipitate toxic megacolon.

Treatment of initial episode:

• Metronidazole is the drug of choice for the initial episode of mild to moderate CDI. The dosage is 500 mg orally three times per day for 10 to 14 days.
• Vancomycin is the drug of choice for an initial episode of severe CDI. The dosage is 125 mg orally four times per day for 10 to 14 days.
• Vancomycin administered orally (and per rectum if ileus is present) with or without intravenously administered metronidazole is the regimen of choice for the treatment of severe complicated CDI. The vancomycin dosage is 500 mg orally four times per day and 500 mg in approximately 100 mL normal saline per rectum every six hours as a retention enema, and the metronidazole dosage is 500 mg intravenously every eight hours.

Severely ill patients:

Consider colectomy for severely ill patients. Monitoring the serum lactate level and the peripheral blood white blood cell count may be helpful in prompting a decision to operate because a serum lactate level rising to 5 mmol/L and a white blood cell count rising to 50,000 cells per mL have been associated with greatly increased perioperative mortality. If surgical management is necessary, perform subtotal colectomy with preservation of the rectum.

Treatment of recurrences:

• Treatment of the first recurrence of CDI is usually with the same regimen as for the initial episode but should be stratified by disease severity (mild-to-moderate, severe, or severe complicated) as is recommended for treatment of the initial CDI episode.
• Do not use metronidazole beyond the first recurrence of CDI or for long-term chronic therapy because of potential for cumulative neurotoxicity.
• Treatment of the second or later recurrence of CDI with vancomycin therapy using a tapered and/or pulse regimen is the preferred next strategy.

Probiotics:

Administration of currently available probiotics is not recommended to prevent primary CDI as there are limited data to support this approach and there is a potential risk of bloodstream infection.

Source: Cohen SH, Gerding DH, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infection Control and Hospital Epidemiology. 2010;31(5):431–455.

National Response, Localized Attention

Dr. Kavanagh of Health Watch USA says that more information about C. diff is needed, particularly publicly available numbers of infections at hospitals. Some states require those figures to be reported, but most don’t. And there is no current federal mandate on reporting of C. diff cases, although acute-care hospitals will be required to report C. diff infection rates starting in 2013.

“We really have scant data,” he says. “There is not a lot of reporting if you look at the nation on a whole. And I think that underscores one of the reasons why you need to have data for action. You need to have reporting of these organisms to the National Healthcare Safety Network so that the CDC can monitor and can make plans and can do effective interventions.

“You want to know where the areas of highest infection are,” he adds. “You want to know what interventions work and don’t work. If you don’t have a national coordinated reporting system, it really makes it difficult to address the problem. C. diff is going to be much harder to control than MRSA or other bacteria because it changes into a hard-to-kill dormant spore stage and then re-occurs at some point.”

The Centers for Medicare & Medicaid Services (CMS) has proposed adding C. diff infections to the list of hospital-acquired conditions that will not be reimbursable. It is widely hoped that such a measure will go a long way toward stamping out the problem.

Dr. Kobaidze of Emory notes that C. diff is a dynamic problem, always adapting and posing new challenges. And hospitalists should be more involved in answering these questions through research. One recent question, she points out, is whether proton pump inhibitor use is related to the rise of C. diff.

Ultimately, though, controlling C. diff in hospitals might come down to what is done day to day inside the hospital. And hospitalists can play a big role.

Danielle Scheurer, MD, MSCR, SFHM, a hospitalist and medical director of quality at the Medical University of South Carolina in Charleston, says that a full-time pharmacist on the hospital’s antimicrobial stewardship committee is always reviewing antibiotic prescriptions and is prepared to flag cases in which a broad-spectrum is used when one with a more narrow scope might be more appropriate.

The hospital has done its best, as part of its “renovation cycle,” to standardize the layouts of rooms “so that the second you open the door you know exactly where the alcohol gel is and where the soap and the sink is going to be.” The idea is to make compliance as “mindless” as possible. Such efforts can be hampered by structural limitations though, she says.

HM group leaders, she suggests, can play an important part simply by being good role models—gowning and gloving without complaint before entering high-risk rooms and reinforcing the message that such efforts have real effects on patient safety.

But she also acknowledges that “it always sounds easy....There has to be some level of redundancy built into the hospital system. This is more of a system thing than the individual hospitalist.”

One level of redundancy at MUSC that has been particularly effective, she says, are “secret shoppers” who keep an eye out for medical teams that might not be washing their hands as they go in and out of high-risk rooms. Each unit is responsible for their hand hygiene numbers—which include both self-reported figures and those obtained by the secret onlookers—and those numbers are made available to the hospital.

Those units with the best numbers are sometimes given a reward, such as a pizza party, but it’s colleagues’ knowledge of the numbers that matters most, she says.

“That, in and of itself, is a powerful motivator,” Dr. Scheurer says. “We bring it to all of our quality operations meetings, all the administrators, the CEO, the CMO. It’s very motivating for every unit. They don’t want to be the trailing unit.”

Tom Collins is a freelance medical writer based in Miami.

References

1. Orenstein R, Aronhalt KC, McManus JE Jr., Fedraw LA. A targeted strategy to wipe out Clostridium difficile. Infect Control Hosp Epidemiol. 2011;32(11):1137-1139.
2. Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53(1):42-48.

What Hospitalists Can Do

Listen to Dr. Gould

Here are suggestions, as provided by ID experts and hospitalist leaders, on what hospitalists can do to battle C. diff infections:

Short-term steps:

• Wash hands before entering and upon leaving rooms occupied by patients with C. diff infections and those strongly suspected of having C. diff infections.
• Continue using alcohol-based hand sanitizers in addition to hand washing to prevent other types of outbreaks.
• Ensure that infected patients, and those suspected of being infected, are isolated, possibly even for 48 hours after diarrhea resolves, as research shows the patients can still transmit the spores.
• In units with high C. diff rates, consider universal gloving, not just for patients with known infection.
• Use more highly sensitive tests, such as polymerase chain reaction, or PCR, rather than enzyme immunoassays to more efficiently identify affected patients.
• Avoid testing patients with formed stools.
• Ensure that rooms of infected patients and patients strongly suspected of being infected are cleaned with a hypochlorite solution.
• Taper the use of broad-spectrum antibiotics in non-C. diff patients after test results are obtained.
• Encourage patients to question their healthcare practitioners about hand hygiene and use of antibiotics.

Long-term steps:

• Be involved with your hospital’s antimicrobial stewardship program.
• Conduct research into C. diff to explore its causes and treatments.
• Be a good role model for the rest of your group, emphasizing good practices and a strong patient-safety message.

Listen to Dr. Gould

At 480-bed Emory University Hospital Midtown in Atlanta, the physicians and staff seemingly are doing all the right things to foil one of hospital’s archenemies: Clostridium difficile. The bacteria, better known as C. diff, is responsible for a sharp rise in hospital-acquired infections over the past decade, rivaling even MRSA.

In 2010, Emory Midtown launched a campaign to boost awareness of the importance of hand washing before and after treating patients infected with C. diff and those likely to be infected. They also began using the polymerase-chain-reaction-based assay to detect the bacteria, a test with much higher sensitivity that helps to more efficiently identify those infected so control measures can be more prompt and targeted. They use a hypochlorite mixture to clean the rooms of those infected, which is considered a must. And a committee monitors the use of antibiotics to prevent overuse—often the scapegoat for the rise of the hard-to-kill bacteria.

Still, at Emory, the rate of C. diff is about the same as the national average, says hospitalist Ketino Kobaidze, MD, assistant professor at the Emory University School of Medicine and a member of the antimicrobial stewardship and infectious disease control committees at Midtown. While Dr. Kobaidze says her institution is doing a good job of trying to keep C. diff under control, she thinks hospitalists can do more.

“My feeling is that we are not as involved as we’re supposed to be,” she says. “I think we need to be a little bit more proactive, be involved in committees and research activities across the hospital.”

You Are Not Alone

The experience at Emory Midtown is far from unusual—healthcare facilities, and hospitalists, across the country have seen healthcare-related C. diff cases more than double since 2001 to between 400,000 and 500,000 a year, says Carolyn Gould, MD, a medical epidemiologist in the division of healthcare quality promotion at the Centers for Disease Control and Prevention (CDC) in Atlanta.

Hospitalists, whether they realize it or not, are intimately involved in how well the C. diff outbreak is controlled. Infectious-disease (ID) specialists say hospitalists are perfectly situated to make an impact in efforts to help curb the outbreak.

“Hospitalists are critical to this effort,” Dr. Gould says. “They’re in the hospital day in and day out, and they’re constantly interacting with the patients, staff, and administration. They’re often the first on the scene to see a patient who might have suddenly developed diarrhea; they’re the first to react. I think they’re in a prime position to play a leadership role to prevent C. diff infections.”

They’re also situated well to work with infection-control experts on antimicrobial stewardship programs, she says.

“I look at hospitalists just like I would have looked at internists managing their own patients 15 years ago,” says Stuart Cohen, MD, an ID expert with the University of California at Davis and a fellow with the Infectious Diseases Society of America who was lead author of the latest published IDSA guidelines on C. diff treatment. “And so they’re the first-line people.”

continued below...

Mayo Shows How a Simple Step Can Make Big Difference in C. Diff

Listen to Dr. Gould

Sometimes even when it comes to a huge problem like widespread bacterial infections, simplicity is best.

The Mayo Clinic, in a project to cut the rate of C. diff infections, asked its workers to do one extra thing: Wipe down high-touch areas with bleach wipes. The effort worked; infections were all but eradicated in units that had been having five to seven infections per month.

The results of the project, recently published in Infectious Control and Hospital Epidemiology, show the importance of simple steps as long as they’re carried out regularly and thoroughly.¹

The project began when Robert Orenstein, DO, associate professor of medicine in infectious diseases who then worked in Rochester, Minn., established a surveillance network for C. diff infections at Mayo Clinic at the time when such infections were being noted more widely throughout the U.S. and Canada. The network began tracking the cases and found that one inpatient medical unit primarily composed of patients with gastrointestinal diseases had a C. diff rate 10 times higher than the rest of the hospital. Surveillance also showed that universally gloved hematology and oncology units had substantially lower rates of C. diff infection despite high-risk patients.

Dr. Orenstein knew he had to make a change in the GI unit, but it wasn’t feasible to institute universal gloving, so he turned to bleach wipes.

Dr. Orenstein

Twice a day, housekeeping staff wiped down all “high-touch” areas (light switches, toilet handles, bed rails) in all of the rooms. The wipes contain 0.55% sodium hypochlorite. Within six months, the number of C. diff cases fell to almost zero.

“We were just in shock,” Dr. Orenstein says. He attributed the improvement to a reduction in the “colonization pressure”—if a high concentration of patients with C. diff can cause abundant transmissions quickly, the opposite is also true.

The greatly improved figures were shared with housekeeping, which initially complained about the smell but were encouraged to keep doors open and rooms ventilated. The bleach wipes, which Dr. Orenstein acknowledges mean an additional expense, leave a white residue when dry, so the surfaces are wiped down with water after the recommended contact time.

Dr. Orenstein notes that the results came even without a change in hand hygiene, which he had deemed not feasible because of the hospital’s lack of sinks. He isn’t diminishing the importance of hand washing, but the project does show how effective a single step can be.

The key, Dr. Orenstein adds, might be that it was just one change involving just one group of staff. “Why we think it was so effective is it was really one group that had to change their behavior and we worked with them, educated them,” he says.

He emphasizes that the wipes don’t come at the expense of other measures, like thorough cleaning of all rooms and antibiotic stewardship programs.

“You do all of those and do them well,” he says, “then you get the reduction of C. diff in the hospital.”

A Tough Bug

Believed to be aided largely by the use of broad-spectrum antibiotics that knock out the colon’s natural flora, C. diff in the hospital—as well as nursing homes and acute-care facilities—has raged for much of the past decade. Its rise is tied to the emergence of a new hypervirulent strain known as BI/NAP1/027, or NAP1 for short. The strain is highly resistant to fluoroquinolones, such as ciprofloxacin and levofloxacin, which are used often in healthcare settings.

“A fluoroquinolone will wipe out a lot of your normal flora in your gut,” Dr. Gould says. “But it won’t wipe out C. diff, in particular this hypervirulent strain. And so this strain can flourish in the presence of fluoroquinolones.” The strain produces up to 15 to 20 times more toxins than other C. diff strains, according to some data, she adds.

Vancomycin (Vanconin) and metronidazole (Flagyl) are the most common antibiotics used to treat patients infected with C. diff. Mortality rates are higher among the elderly, largely because of their weaker immune system, Dr. Gould says. Studies have generally shown mortality rates of 10% or a bit lower.¹

More recent studies have shown that the number of hospital-related C. diff cases might have begun to level off in 2008 and 2009. Dr. Gould says she thinks the leveling off is for real, but there is debate over what the immediate future holds.

“There’s a lot of work and initiatives, especially state-based initiatives, that are being done in hospitals. And there’s reason to believe they’re effective,” she says, adding it’s harder to get a good picture of the problem in long-term care facilities and in the community.

Dr. Cohen with the IDSA says it’s too soon to say whether the problem is hitting a plateau. “CDC data are always a couple of years behind,” he says. “Until you see another data point, you can’t tell whether that’s just a transient flattening and whether it’s going to keep going up or not.”

Kevin Kavanagh, MD, founder of the patient advocacy group Health Watch USA and a retired otolaryngologist in Kentucky who has taken a keen interest in the C. diff problem, says he doesn’t think the end of the tunnel is within view yet.

“I think C. diff is going to get worse before it gets better,” Dr. Kavanagh says. “And that’s not necessarily because the healthcare profession isn’t doing due diligence. This is a tough organism.—it can be tough to treat and can be very tough to kill.”

The Best Defense?

Because C. diff lives within protective spores, sound hand hygiene practices and room-cleaning practices are essential for keeping infections to a minimum. Alcohol-based hand sanitizers, effective against other organisms including MRSA, do not kill C. diff. The bacteria must be mechanically removed through hand washing.

And even hand washing might not be totally effective at getting rid of the spores, which means it’s important for healthcare workers to gown and glove in high-risk rooms.

Sodium hypochlorite solutions, or bleach mixtures, have to be used to clean rooms occupied by patients with C. diff, and the prevailing thought is to clean the rooms of patients suspected of having C. diff, even if those cases might not be confirmed.

Equally important to cleaning and hand washing is systemwide emphasis on antibiotic stewardship. A 2011 study at the State University of New York Buffalo found that the risk of a C. diff infection rose with the number of antibiotics taken.²

If someone is very sick and you’re not sure what is going on, it’s very reasonable to treat them empirically with broad-spectrum antibiotics. The important thing is that you send the appropriate cultures before so that you know what you’re treating and you can optimize those antibiotics with daily assessments.

—Carolyn Gould, MD, medical epidemiologist, division of healthcare quality promotion, Centers of Disease Control and Prevention, Atlanta

While a broad-spectrum antibiotic might be necessary at first, once the results of cultures are received, the treatment should be finely tailored to kill only the problem bacteria so that the body’s natural defenses aren’t broken down, Dr. Gould explains.

“If someone is very sick and you’re not sure what is going on, it’s very reasonable to treat them empirically with broad-spectrum antibiotics,” she says. “The important thing is that you send the appropriate cultures before so that you know what you’re treating and you can optimize those antibiotics with daily assessments.”

Dr. Cohen

It’s clear why an overreliance on broad-spectrum drugs prevails in U.S. health settings, Dr. Cohen acknowledges. Recent literature suggests treating critically ill patients with wide-ranging antimicrobials as the mortality rate can be twice as high with narrower options. “I think people have gotten very quick to give broad-spectrum therapy,” he says.

continued below...

Knocking Out Clostridium Difficile

Listen to Dr. Gould

Here are the guidelines on treatment of C. diff infections (CDI) as recommended by the Infectious Diseases Society of America:

First steps:

• Discontinue therapy with the inciting antimicrobial agent(s) as soon as possible as this may influence the risk of CDI recurrence.
• When severe or complicated CDI is suspected, initiate empirical treatment as soon as the diagnosis is suspected.
• If the stool toxin assay result is negative, the decision to initiate, stop, or continue treatment must be individualized.
• If possible, avoid use of antiperistaltic agents as they may obscure symptoms and precipitate toxic megacolon.

Treatment of initial episode:

• Metronidazole is the drug of choice for the initial episode of mild to moderate CDI. The dosage is 500 mg orally three times per day for 10 to 14 days.
• Vancomycin is the drug of choice for an initial episode of severe CDI. The dosage is 125 mg orally four times per day for 10 to 14 days.
• Vancomycin administered orally (and per rectum if ileus is present) with or without intravenously administered metronidazole is the regimen of choice for the treatment of severe complicated CDI. The vancomycin dosage is 500 mg orally four times per day and 500 mg in approximately 100 mL normal saline per rectum every six hours as a retention enema, and the metronidazole dosage is 500 mg intravenously every eight hours.

Severely ill patients:

Consider colectomy for severely ill patients. Monitoring the serum lactate level and the peripheral blood white blood cell count may be helpful in prompting a decision to operate because a serum lactate level rising to 5 mmol/L and a white blood cell count rising to 50,000 cells per mL have been associated with greatly increased perioperative mortality. If surgical management is necessary, perform subtotal colectomy with preservation of the rectum.

Treatment of recurrences:

• Treatment of the first recurrence of CDI is usually with the same regimen as for the initial episode but should be stratified by disease severity (mild-to-moderate, severe, or severe complicated) as is recommended for treatment of the initial CDI episode.
• Do not use metronidazole beyond the first recurrence of CDI or for long-term chronic therapy because of potential for cumulative neurotoxicity.
• Treatment of the second or later recurrence of CDI with vancomycin therapy using a tapered and/or pulse regimen is the preferred next strategy.

Probiotics:

Administration of currently available probiotics is not recommended to prevent primary CDI as there are limited data to support this approach and there is a potential risk of bloodstream infection.

Source: Cohen SH, Gerding DH, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infection Control and Hospital Epidemiology. 2010;31(5):431–455.

National Response, Localized Attention

Dr. Kavanagh of Health Watch USA says that more information about C. diff is needed, particularly publicly available numbers of infections at hospitals. Some states require those figures to be reported, but most don’t. And there is no current federal mandate on reporting of C. diff cases, although acute-care hospitals will be required to report C. diff infection rates starting in 2013.

“We really have scant data,” he says. “There is not a lot of reporting if you look at the nation on a whole. And I think that underscores one of the reasons why you need to have data for action. You need to have reporting of these organisms to the National Healthcare Safety Network so that the CDC can monitor and can make plans and can do effective interventions.

“You want to know where the areas of highest infection are,” he adds. “You want to know what interventions work and don’t work. If you don’t have a national coordinated reporting system, it really makes it difficult to address the problem. C. diff is going to be much harder to control than MRSA or other bacteria because it changes into a hard-to-kill dormant spore stage and then re-occurs at some point.”

The Centers for Medicare & Medicaid Services (CMS) has proposed adding C. diff infections to the list of hospital-acquired conditions that will not be reimbursable. It is widely hoped that such a measure will go a long way toward stamping out the problem.

Dr. Kobaidze of Emory notes that C. diff is a dynamic problem, always adapting and posing new challenges. And hospitalists should be more involved in answering these questions through research. One recent question, she points out, is whether proton pump inhibitor use is related to the rise of C. diff.

Ultimately, though, controlling C. diff in hospitals might come down to what is done day to day inside the hospital. And hospitalists can play a big role.

Danielle Scheurer, MD, MSCR, SFHM, a hospitalist and medical director of quality at the Medical University of South Carolina in Charleston, says that a full-time pharmacist on the hospital’s antimicrobial stewardship committee is always reviewing antibiotic prescriptions and is prepared to flag cases in which a broad-spectrum is used when one with a more narrow scope might be more appropriate.

The hospital has done its best, as part of its “renovation cycle,” to standardize the layouts of rooms “so that the second you open the door you know exactly where the alcohol gel is and where the soap and the sink is going to be.” The idea is to make compliance as “mindless” as possible. Such efforts can be hampered by structural limitations though, she says.

HM group leaders, she suggests, can play an important part simply by being good role models—gowning and gloving without complaint before entering high-risk rooms and reinforcing the message that such efforts have real effects on patient safety.

But she also acknowledges that “it always sounds easy....There has to be some level of redundancy built into the hospital system. This is more of a system thing than the individual hospitalist.”

One level of redundancy at MUSC that has been particularly effective, she says, are “secret shoppers” who keep an eye out for medical teams that might not be washing their hands as they go in and out of high-risk rooms. Each unit is responsible for their hand hygiene numbers—which include both self-reported figures and those obtained by the secret onlookers—and those numbers are made available to the hospital.

Those units with the best numbers are sometimes given a reward, such as a pizza party, but it’s colleagues’ knowledge of the numbers that matters most, she says.

“That, in and of itself, is a powerful motivator,” Dr. Scheurer says. “We bring it to all of our quality operations meetings, all the administrators, the CEO, the CMO. It’s very motivating for every unit. They don’t want to be the trailing unit.”

Tom Collins is a freelance medical writer based in Miami.

References

1. Orenstein R, Aronhalt KC, McManus JE Jr., Fedraw LA. A targeted strategy to wipe out Clostridium difficile. Infect Control Hosp Epidemiol. 2011;32(11):1137-1139.
2. Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53(1):42-48.

What Hospitalists Can Do

Listen to Dr. Gould

Here are suggestions, as provided by ID experts and hospitalist leaders, on what hospitalists can do to battle C. diff infections:

Short-term steps:

• Wash hands before entering and upon leaving rooms occupied by patients with C. diff infections and those strongly suspected of having C. diff infections.
• Continue using alcohol-based hand sanitizers in addition to hand washing to prevent other types of outbreaks.
• Ensure that infected patients, and those suspected of being infected, are isolated, possibly even for 48 hours after diarrhea resolves, as research shows the patients can still transmit the spores.
• In units with high C. diff rates, consider universal gloving, not just for patients with known infection.
• Use more highly sensitive tests, such as polymerase chain reaction, or PCR, rather than enzyme immunoassays to more efficiently identify affected patients.
• Avoid testing patients with formed stools.
• Ensure that rooms of infected patients and patients strongly suspected of being infected are cleaned with a hypochlorite solution.
• Taper the use of broad-spectrum antibiotics in non-C. diff patients after test results are obtained.
• Encourage patients to question their healthcare practitioners about hand hygiene and use of antibiotics.

Long-term steps:

• Be involved with your hospital’s antimicrobial stewardship program.
• Conduct research into C. diff to explore its causes and treatments.
• Be a good role model for the rest of your group, emphasizing good practices and a strong patient-safety message.

Listen to Dr. Gould

At 480-bed Emory University Hospital Midtown in Atlanta, the physicians and staff seemingly are doing all the right things to foil one of hospital’s archenemies: Clostridium difficile. The bacteria, better known as C. diff, is responsible for a sharp rise in hospital-acquired infections over the past decade, rivaling even MRSA.

In 2010, Emory Midtown launched a campaign to boost awareness of the importance of hand washing before and after treating patients infected with C. diff and those likely to be infected. They also began using the polymerase-chain-reaction-based assay to detect the bacteria, a test with much higher sensitivity that helps to more efficiently identify those infected so control measures can be more prompt and targeted. They use a hypochlorite mixture to clean the rooms of those infected, which is considered a must. And a committee monitors the use of antibiotics to prevent overuse—often the scapegoat for the rise of the hard-to-kill bacteria.

Still, at Emory, the rate of C. diff is about the same as the national average, says hospitalist Ketino Kobaidze, MD, assistant professor at the Emory University School of Medicine and a member of the antimicrobial stewardship and infectious disease control committees at Midtown. While Dr. Kobaidze says her institution is doing a good job of trying to keep C. diff under control, she thinks hospitalists can do more.

“My feeling is that we are not as involved as we’re supposed to be,” she says. “I think we need to be a little bit more proactive, be involved in committees and research activities across the hospital.”

You Are Not Alone

The experience at Emory Midtown is far from unusual—healthcare facilities, and hospitalists, across the country have seen healthcare-related C. diff cases more than double since 2001 to between 400,000 and 500,000 a year, says Carolyn Gould, MD, a medical epidemiologist in the division of healthcare quality promotion at the Centers for Disease Control and Prevention (CDC) in Atlanta.

Hospitalists, whether they realize it or not, are intimately involved in how well the C. diff outbreak is controlled. Infectious-disease (ID) specialists say hospitalists are perfectly situated to make an impact in efforts to help curb the outbreak.

“Hospitalists are critical to this effort,” Dr. Gould says. “They’re in the hospital day in and day out, and they’re constantly interacting with the patients, staff, and administration. They’re often the first on the scene to see a patient who might have suddenly developed diarrhea; they’re the first to react. I think they’re in a prime position to play a leadership role to prevent C. diff infections.”

They’re also situated well to work with infection-control experts on antimicrobial stewardship programs, she says.

“I look at hospitalists just like I would have looked at internists managing their own patients 15 years ago,” says Stuart Cohen, MD, an ID expert with the University of California at Davis and a fellow with the Infectious Diseases Society of America who was lead author of the latest published IDSA guidelines on C. diff treatment. “And so they’re the first-line people.”

continued below...

Mayo Shows How a Simple Step Can Make Big Difference in C. Diff

Listen to Dr. Gould

Sometimes even when it comes to a huge problem like widespread bacterial infections, simplicity is best.

The Mayo Clinic, in a project to cut the rate of C. diff infections, asked its workers to do one extra thing: Wipe down high-touch areas with bleach wipes. The effort worked; infections were all but eradicated in units that had been having five to seven infections per month.

The results of the project, recently published in Infectious Control and Hospital Epidemiology, show the importance of simple steps as long as they’re carried out regularly and thoroughly.¹

The project began when Robert Orenstein, DO, associate professor of medicine in infectious diseases who then worked in Rochester, Minn., established a surveillance network for C. diff infections at Mayo Clinic at the time when such infections were being noted more widely throughout the U.S. and Canada. The network began tracking the cases and found that one inpatient medical unit primarily composed of patients with gastrointestinal diseases had a C. diff rate 10 times higher than the rest of the hospital. Surveillance also showed that universally gloved hematology and oncology units had substantially lower rates of C. diff infection despite high-risk patients.

Dr. Orenstein knew he had to make a change in the GI unit, but it wasn’t feasible to institute universal gloving, so he turned to bleach wipes.

Dr. Orenstein

Twice a day, housekeeping staff wiped down all “high-touch” areas (light switches, toilet handles, bed rails) in all of the rooms. The wipes contain 0.55% sodium hypochlorite. Within six months, the number of C. diff cases fell to almost zero.

“We were just in shock,” Dr. Orenstein says. He attributed the improvement to a reduction in the “colonization pressure”—if a high concentration of patients with C. diff can cause abundant transmissions quickly, the opposite is also true.

The greatly improved figures were shared with housekeeping, which initially complained about the smell but were encouraged to keep doors open and rooms ventilated. The bleach wipes, which Dr. Orenstein acknowledges mean an additional expense, leave a white residue when dry, so the surfaces are wiped down with water after the recommended contact time.

Dr. Orenstein notes that the results came even without a change in hand hygiene, which he had deemed not feasible because of the hospital’s lack of sinks. He isn’t diminishing the importance of hand washing, but the project does show how effective a single step can be.

The key, Dr. Orenstein adds, might be that it was just one change involving just one group of staff. “Why we think it was so effective is it was really one group that had to change their behavior and we worked with them, educated them,” he says.

He emphasizes that the wipes don’t come at the expense of other measures, like thorough cleaning of all rooms and antibiotic stewardship programs.

“You do all of those and do them well,” he says, “then you get the reduction of C. diff in the hospital.”

A Tough Bug

Believed to be aided largely by the use of broad-spectrum antibiotics that knock out the colon’s natural flora, C. diff in the hospital—as well as nursing homes and acute-care facilities—has raged for much of the past decade. Its rise is tied to the emergence of a new hypervirulent strain known as BI/NAP1/027, or NAP1 for short. The strain is highly resistant to fluoroquinolones, such as ciprofloxacin and levofloxacin, which are used often in healthcare settings.

“A fluoroquinolone will wipe out a lot of your normal flora in your gut,” Dr. Gould says. “But it won’t wipe out C. diff, in particular this hypervirulent strain. And so this strain can flourish in the presence of fluoroquinolones.” The strain produces up to 15 to 20 times more toxins than other C. diff strains, according to some data, she adds.

Vancomycin (Vanconin) and metronidazole (Flagyl) are the most common antibiotics used to treat patients infected with C. diff. Mortality rates are higher among the elderly, largely because of their weaker immune system, Dr. Gould says. Studies have generally shown mortality rates of 10% or a bit lower.¹

More recent studies have shown that the number of hospital-related C. diff cases might have begun to level off in 2008 and 2009. Dr. Gould says she thinks the leveling off is for real, but there is debate over what the immediate future holds.

“There’s a lot of work and initiatives, especially state-based initiatives, that are being done in hospitals. And there’s reason to believe they’re effective,” she says, adding it’s harder to get a good picture of the problem in long-term care facilities and in the community.

Dr. Cohen with the IDSA says it’s too soon to say whether the problem is hitting a plateau. “CDC data are always a couple of years behind,” he says. “Until you see another data point, you can’t tell whether that’s just a transient flattening and whether it’s going to keep going up or not.”

Kevin Kavanagh, MD, founder of the patient advocacy group Health Watch USA and a retired otolaryngologist in Kentucky who has taken a keen interest in the C. diff problem, says he doesn’t think the end of the tunnel is within view yet.

“I think C. diff is going to get worse before it gets better,” Dr. Kavanagh says. “And that’s not necessarily because the healthcare profession isn’t doing due diligence. This is a tough organism.—it can be tough to treat and can be very tough to kill.”

The Best Defense?

Because C. diff lives within protective spores, sound hand hygiene practices and room-cleaning practices are essential for keeping infections to a minimum. Alcohol-based hand sanitizers, effective against other organisms including MRSA, do not kill C. diff. The bacteria must be mechanically removed through hand washing.

And even hand washing might not be totally effective at getting rid of the spores, which means it’s important for healthcare workers to gown and glove in high-risk rooms.

Sodium hypochlorite solutions, or bleach mixtures, have to be used to clean rooms occupied by patients with C. diff, and the prevailing thought is to clean the rooms of patients suspected of having C. diff, even if those cases might not be confirmed.

Equally important to cleaning and hand washing is systemwide emphasis on antibiotic stewardship. A 2011 study at the State University of New York Buffalo found that the risk of a C. diff infection rose with the number of antibiotics taken.²

If someone is very sick and you’re not sure what is going on, it’s very reasonable to treat them empirically with broad-spectrum antibiotics. The important thing is that you send the appropriate cultures before so that you know what you’re treating and you can optimize those antibiotics with daily assessments.

—Carolyn Gould, MD, medical epidemiologist, division of healthcare quality promotion, Centers of Disease Control and Prevention, Atlanta

While a broad-spectrum antibiotic might be necessary at first, once the results of cultures are received, the treatment should be finely tailored to kill only the problem bacteria so that the body’s natural defenses aren’t broken down, Dr. Gould explains.

“If someone is very sick and you’re not sure what is going on, it’s very reasonable to treat them empirically with broad-spectrum antibiotics,” she says. “The important thing is that you send the appropriate cultures before so that you know what you’re treating and you can optimize those antibiotics with daily assessments.”

Dr. Cohen

It’s clear why an overreliance on broad-spectrum drugs prevails in U.S. health settings, Dr. Cohen acknowledges. Recent literature suggests treating critically ill patients with wide-ranging antimicrobials as the mortality rate can be twice as high with narrower options. “I think people have gotten very quick to give broad-spectrum therapy,” he says.

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Knocking Out Clostridium Difficile

Listen to Dr. Gould

Here are the guidelines on treatment of C. diff infections (CDI) as recommended by the Infectious Diseases Society of America:

First steps:

• Discontinue therapy with the inciting antimicrobial agent(s) as soon as possible as this may influence the risk of CDI recurrence.
• When severe or complicated CDI is suspected, initiate empirical treatment as soon as the diagnosis is suspected.
• If the stool toxin assay result is negative, the decision to initiate, stop, or continue treatment must be individualized.
• If possible, avoid use of antiperistaltic agents as they may obscure symptoms and precipitate toxic megacolon.

Treatment of initial episode:

• Metronidazole is the drug of choice for the initial episode of mild to moderate CDI. The dosage is 500 mg orally three times per day for 10 to 14 days.
• Vancomycin is the drug of choice for an initial episode of severe CDI. The dosage is 125 mg orally four times per day for 10 to 14 days.
• Vancomycin administered orally (and per rectum if ileus is present) with or without intravenously administered metronidazole is the regimen of choice for the treatment of severe complicated CDI. The vancomycin dosage is 500 mg orally four times per day and 500 mg in approximately 100 mL normal saline per rectum every six hours as a retention enema, and the metronidazole dosage is 500 mg intravenously every eight hours.

Severely ill patients:

Consider colectomy for severely ill patients. Monitoring the serum lactate level and the peripheral blood white blood cell count may be helpful in prompting a decision to operate because a serum lactate level rising to 5 mmol/L and a white blood cell count rising to 50,000 cells per mL have been associated with greatly increased perioperative mortality. If surgical management is necessary, perform subtotal colectomy with preservation of the rectum.

Treatment of recurrences:

• Treatment of the first recurrence of CDI is usually with the same regimen as for the initial episode but should be stratified by disease severity (mild-to-moderate, severe, or severe complicated) as is recommended for treatment of the initial CDI episode.
• Do not use metronidazole beyond the first recurrence of CDI or for long-term chronic therapy because of potential for cumulative neurotoxicity.
• Treatment of the second or later recurrence of CDI with vancomycin therapy using a tapered and/or pulse regimen is the preferred next strategy.

Probiotics:

Administration of currently available probiotics is not recommended to prevent primary CDI as there are limited data to support this approach and there is a potential risk of bloodstream infection.

Source: Cohen SH, Gerding DH, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA). Infection Control and Hospital Epidemiology. 2010;31(5):431–455.

National Response, Localized Attention

Dr. Kavanagh of Health Watch USA says that more information about C. diff is needed, particularly publicly available numbers of infections at hospitals. Some states require those figures to be reported, but most don’t. And there is no current federal mandate on reporting of C. diff cases, although acute-care hospitals will be required to report C. diff infection rates starting in 2013.

“We really have scant data,” he says. “There is not a lot of reporting if you look at the nation on a whole. And I think that underscores one of the reasons why you need to have data for action. You need to have reporting of these organisms to the National Healthcare Safety Network so that the CDC can monitor and can make plans and can do effective interventions.

“You want to know where the areas of highest infection are,” he adds. “You want to know what interventions work and don’t work. If you don’t have a national coordinated reporting system, it really makes it difficult to address the problem. C. diff is going to be much harder to control than MRSA or other bacteria because it changes into a hard-to-kill dormant spore stage and then re-occurs at some point.”

The Centers for Medicare & Medicaid Services (CMS) has proposed adding C. diff infections to the list of hospital-acquired conditions that will not be reimbursable. It is widely hoped that such a measure will go a long way toward stamping out the problem.

Dr. Kobaidze of Emory notes that C. diff is a dynamic problem, always adapting and posing new challenges. And hospitalists should be more involved in answering these questions through research. One recent question, she points out, is whether proton pump inhibitor use is related to the rise of C. diff.

Ultimately, though, controlling C. diff in hospitals might come down to what is done day to day inside the hospital. And hospitalists can play a big role.

Danielle Scheurer, MD, MSCR, SFHM, a hospitalist and medical director of quality at the Medical University of South Carolina in Charleston, says that a full-time pharmacist on the hospital’s antimicrobial stewardship committee is always reviewing antibiotic prescriptions and is prepared to flag cases in which a broad-spectrum is used when one with a more narrow scope might be more appropriate.

The hospital has done its best, as part of its “renovation cycle,” to standardize the layouts of rooms “so that the second you open the door you know exactly where the alcohol gel is and where the soap and the sink is going to be.” The idea is to make compliance as “mindless” as possible. Such efforts can be hampered by structural limitations though, she says.

HM group leaders, she suggests, can play an important part simply by being good role models—gowning and gloving without complaint before entering high-risk rooms and reinforcing the message that such efforts have real effects on patient safety.

But she also acknowledges that “it always sounds easy....There has to be some level of redundancy built into the hospital system. This is more of a system thing than the individual hospitalist.”

One level of redundancy at MUSC that has been particularly effective, she says, are “secret shoppers” who keep an eye out for medical teams that might not be washing their hands as they go in and out of high-risk rooms. Each unit is responsible for their hand hygiene numbers—which include both self-reported figures and those obtained by the secret onlookers—and those numbers are made available to the hospital.

Those units with the best numbers are sometimes given a reward, such as a pizza party, but it’s colleagues’ knowledge of the numbers that matters most, she says.

“That, in and of itself, is a powerful motivator,” Dr. Scheurer says. “We bring it to all of our quality operations meetings, all the administrators, the CEO, the CMO. It’s very motivating for every unit. They don’t want to be the trailing unit.”

Tom Collins is a freelance medical writer based in Miami.

References

1. Orenstein R, Aronhalt KC, McManus JE Jr., Fedraw LA. A targeted strategy to wipe out Clostridium difficile. Infect Control Hosp Epidemiol. 2011;32(11):1137-1139.
2. Stevens V, Dumyati G, Fine LS, Fisher SG, van Wijngaarden E. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53(1):42-48.

What Hospitalists Can Do

Listen to Dr. Gould

Here are suggestions, as provided by ID experts and hospitalist leaders, on what hospitalists can do to battle C. diff infections:

Short-term steps:

• Wash hands before entering and upon leaving rooms occupied by patients with C. diff infections and those strongly suspected of having C. diff infections.
• Continue using alcohol-based hand sanitizers in addition to hand washing to prevent other types of outbreaks.
• Ensure that infected patients, and those suspected of being infected, are isolated, possibly even for 48 hours after diarrhea resolves, as research shows the patients can still transmit the spores.
• In units with high C. diff rates, consider universal gloving, not just for patients with known infection.
• Use more highly sensitive tests, such as polymerase chain reaction, or PCR, rather than enzyme immunoassays to more efficiently identify affected patients.
• Avoid testing patients with formed stools.
• Ensure that rooms of infected patients and patients strongly suspected of being infected are cleaned with a hypochlorite solution.
• Taper the use of broad-spectrum antibiotics in non-C. diff patients after test results are obtained.
• Encourage patients to question their healthcare practitioners about hand hygiene and use of antibiotics.

Long-term steps:

• Be involved with your hospital’s antimicrobial stewardship program.
• Conduct research into C. diff to explore its causes and treatments.
• Be a good role model for the rest of your group, emphasizing good practices and a strong patient-safety message.

The hospitalist concept was established on the foundation of timely, informative handoffs to primary-care physicians (PCPs) once a patient’s hospital stay is complete. With sicker patients and shorter hospital stays, pending test results, and complex post-discharge medication regimens to sort out, this handoff is crucial to successful discharges. But what if a discharged patient can’t get in to see the PCP, or has no established PCP?

Recent research on hospital readmissions by the Dartmouth Atlas Project found that only 42% of hospitalized Medicare patients had any contact with a primary-care clinician within 14 days of discharge.¹ For patients with ongoing medical needs, such missed connections are a major contributor to hospital readmissions, and thus a target for hospitals and HM groups wanting to control their readmission rates before Medicare imposes reimbursement penalties starting in October 2012 (see “Value-Based Purchasing Raises the Stakes,” May 2011, p. 1).

One proposed solution is the post-discharge clinic, typically located on or near a hospital’s campus and staffed by hospitalists, PCPs, or advanced-practice nurses. The patient can be seen once or a few times in the post-discharge clinic to make sure that health education started in the hospital is understood and followed, and that prescriptions ordered in the hospital are being taken on schedule.

Mark V. Williams, MD, FACP, FHM, professor and chief of the division of hospital medicine at Northwestern University’s Feinberg School of Medicine in Chicago, describes hospitalist-led post-discharge clinics as “Band-Aids for an inadequate primary-care system.” What would be better, he says, is focusing on the underlying problem and working to improve post-discharge access to primary care. Dr. Williams acknowledges, however, that sometimes a patch is needed to stanch the blood flow—e.g., to better manage care transitions—while waiting on healthcare reform and medical homes to improve care coordination throughout the system.

Working in a post-discharge clinic might seem like “a stretch for many hospitalists, especially those who chose this field because they didn’t want to do outpatient medicine,” says Lauren Doctoroff, MD, a hospitalist who directs a post-discharge clinic at Beth Israel Deaconess Medical Center (BIDMC) in Boston. “But there are times when it may be appropriate for hospital-based doctors to extend their responsibility out of the hospital.”

Dr. Doctoroff also says that working in such a clinic can be practice-changing for hospitalists. “All of a sudden, you have a different view of your hospitalized patients, and you start to ask different questions while they’re in the hospital than you ever did before,” she explains.

What is a Post-Discharge Clinic?

click for large version

The post-discharge clinic, also known as a transitional-care clinic or after-care clinic, is intended to bridge medical coverage between the hospital and primary care. The clinic at BIDMC is for patients affiliated with its Health Care Associates faculty practice “discharged from either our hospital or another hospital, who need care that their PCP or specialist, because of scheduling conflicts, cannot provide within the needed time frame,” Dr. Doctoroff says.

Four hospitalists from BIDMC’s large HM group were selected to staff the clinic. The hospitalists work in one-month rotations (a total of three months on service per year), and are relieved of other responsibilities during their month in clinic. They provide five half-day clinic sessions per week, with a 40-minute-per-patient visit schedule. Thirty minutes are allotted for patients referred from the hospital’s ED who did not get admitted to the hospital but need clinical follow-up.

The clinic is based in a BIDMC-affiliated primary-care practice, “which allows us to use its administrative structure and logistical support,” Dr. Doctoroff explains. “A hospital-based administrative service helps set up outpatient visits prior to discharge using computerized physician order entry and a scheduling algorhythm.” (See Figure 1) Patients who can be seen by their PCP in a timely fashion are referred to the PCP office; if not, they are scheduled in the post-discharge clinic. “That helps preserve the PCP relationship, which I think is paramount,” she says.

The first two years were spent getting the clinic established, but in the near future, BIDMC will start measuring such outcomes as access to care and quality. “But not necessarily readmission rates,” Dr. Doctoroff adds. “I know many people think of post-discharge clinics in the context of preventing readmissions, although we don’t have the data yet to fully support that. In fact, some readmissions may result from seeing a doctor. If you get a closer look at some patients after discharge and they are doing badly, they are more likely to be readmitted than if they had just stayed home.” In such cases, readmission could actually be a better outcome for the patient, she notes.

Dr. Doctoroff describes a typical user of her post-discharge clinic as a non-English-speaking patient who was discharged from the hospital with severe back pain from a herniated disk. “He came back to see me 10 days later, still barely able to walk. He hadn’t been able to fill any of the prescriptions from his hospital stay. Within two hours after I saw him, we got his meds filled and outpatient services set up,” she says. “We take care of many patients like him in the hospital with acute pain issues, whom we discharge as soon as they can walk, and later we see them limping into outpatient clinics. It makes me think differently now about how I plan their discharges.”

We do medication reconciliation, reassessments, and follow-ups with lab tests. We also try to assess who is more likely to be a no-show, and who needs more help with scheduling follow-up appointments.

—Shay Martinez, MD, hospitalist, medical director, Harborview Medical Center, Seattle

Who else needs these clinics? Dr. Doctoroff suggests two ways of looking at the question.

“Even for a simple patient admitted to the hospital, that can represent a significant change in the medical picture—a sort of sentinel event. In the discharge clinic, we give them an opportunity to review the hospitalization and answer their questions,” she says. “A lot of information presented to patients in the hospital is not well heard, and the initial visit may be their first time to really talk about what happened.” For other patients with conditions such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or poorly controlled diabetes, treatment guidelines might dictate a pattern for post-discharge follow-up—for example, medical visits in seven or 10 days.

In Seattle, Harborview Medical Center established its After Care Clinic, staffed by hospitalists and nurse practitioners, to provide transitional care for patients discharged from inpatient wards or the ED in need of follow-up, says medical director and hospitalist Shay Martinez, MD. A second priority is to see any CHF patient within 48 hours of discharge.

“We try to limit patients to a maximum of three visits in our clinic,” she says. “At that point, we help them get established in a medical home, either here in one of our primary-care clinics, or in one of the many excellent community clinics in the area.

“This model works well with our patient population. We actually try to do primary care on the inpatient side as well. Our hospitalists are specialized in that approach, given our patient population. We see a lot of immigrants, non-English speakers, people with low health literacy, and the homeless, many of whom lack primary care,” Dr. Martinez says. “We do medication reconciliation, reassessments, and follow-ups with lab tests. We also try to assess who is more likely to be a no-show, and who needs more help with scheduling follow-up appointments.”

Clinical coverage of post-discharge clinics varies by setting, staffing, and scope. If demand is low, hospitalists or ED physicians can be called off the floor to see patients who return to the clinic, or they could staff the clinic after their hospitalist shift ends. Post-discharge clinic staff whose schedules are light can flex into providing primary-care visits in the clinic. Post-discharge can also could be provided in conjunction with—or as an alternative to—physician house calls to patients’ homes. Some post-discharge clinics work with medical call centers or telephonic case managers; some even use telemedicine.

It also could be a growth opportunity for hospitalist practices. “It is an exciting potential role for hospitalists interested in doing a little outpatient care,” Dr. Martinez says. “This is also a good way to be a safety net for your safety-net hospital.”

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What Do PCPs Think? It May Be Harder than It Looks

Listen to Dr. Doctoroff

Although some PCPs instinctively will be suspicious of a hospitalist-run post-discharge clinic, it should be possible to clearly limit the service to short-term, immediate-post-hospital encounters focused on issues related to patients unable to get timely access to primary care, according to Dr. Doctoroff.

“I think there is a diversity of opinion by PCPs,” she says. “Some doctors really believe that it interferes with the patient-doctor relationship. But after we’ve been here for a couple of years, we’ve built up credibility with many providers.”

Charles Cutler, MD, FACP, a general internist with a practice in Norristown, Pa., and a member of the ACP’s Board of Regents, says the post-discharge clinic is “a novel idea.”

“I’d be very curious to see if this really is a way to provide better and more cost-effective care,” adds Dr. Cutler, who normally retains management of his own patients when they are hospitalized but agrees that hospitals need to find a solution for lapses in care transitions.

Even so, he says, establishing an outpatient clinic presence may be more difficult than many hospitalists appreciate. “You can’t just put a doc in a room. That physician needs equipment, scheduling, and support staff,” he says. “In our small practice, we employ one person just to ensure that each patient chart is up to date. The overhead necessary to replicate a typical medical office, even one merely providing a transition of care, could be substantial.”

Dr. Cutler emphasizes such office-based challenges as billing, which is distinctly different from hospital billing, and credentialing by insurance companies.

“There are many aspects that have to be thought through. If you see the patient, you need to make yourself available for follow-up calls, because you’ve created a relationship,” he says. “I’m a believer that hospital medicine requires a degree of specialization. But so does an office practice.”

Dr. Cutler acknowledges that some PCPs will be resentful of post-discharge clinics. “But if you don’t like a hospitalist-run discharge clinic, then you have a responsibility to rearrange your schedule to accommodate patients after their hospital discharge,” he says.

Partner with Community

Tallahassee (Fla.) Memorial Hospital (TMH) in February launched a transitional-care clinic in collaboration with faculty from Florida State University, community-based health providers, and the local Capital Health Plan. Hospitalists don’t staff the clinic, but the HM group is its major source of referrals, says Dean Watson, MD, chief medical officer at TMH. Patients can be followed for up to eight weeks, during which time they get comprehensive assessments, medication review and optimization, and referral by the clinic social worker to a PCP and to available community services.

“Three years ago, we came up with the idea for a patient population we know is at high risk for readmission. Why don’t we partner with organizations in the community, form a clinic, teach students and residents, and learn together?” Dr. Watson says. “In addition to the usual patients, TMH targets those who have been readmitted to the hospital three times or more in the past year.”

The clinic, open five days a week, is staffed by a physician, nurse practitioner, telephonic nurse, and social worker, and also has a geriatric assessment clinic.

“We set up a system to identify patients through our electronic health record, and when they come to the clinic, we focus on their social environment and other non-medical issues that might cause readmissions,” he says. The clinic has a pharmacy and funds to support medications for patients without insurance. “In our first six months, we reduced emergency room visits and readmissions for these patients by 68 percent.”

One key partner, Capital Health Plan, bought and refurbished a building, and made it available for the clinic at no cost. Capital’s motivation, says Tom Glennon, a senior vice president for the plan, is its commitment to the community and to community service.

“We’re a nonprofit HMO. We’re focused on what we can do to serve the community, and we’re looking at this as a way for the hospital to have fewer costly, unreimbursed bouncebacks,” Glennon says. “That’s a win-win for all of us.”

Most of the patients who use the clinic are not members of Capital Health Plan, Glennon adds. “If we see CHP members turning up at the transitions clinic, then we have a problem—a breakdown in our case management,” he explains. “Our goal is to have our members taken care of by primary-care providers.”

Hard Data? Not So Fast

How many post-discharge clinics are in operation today is not known. Fundamental financial data, too, are limited, but some say it is unlikely a post-discharge clinic will cover operating expenses from billing revenues alone.

Thus, such clinics will require funding from the hospital, HM group, health system, or health plans, based on the benefits the clinic provides to discharged patients and the impact on 30-day readmissions (for more about the logistical challenges post-discharge clinics present, see “What Do PCPs Think?”).

Some also suggest that many of the post-discharge clinics now in operation are too new to have demonstrated financial impact or return on investment. “We have not yet been asked to show our financial viability,” Dr. Doctoroff says. “I think the clinic leadership thinks we are fulfilling other goals for now, such as creating easier access for their patients after discharge.”

Amy Boutwell, MD, MPP, a hospitalist at Newton Wellesley Hospital in Massachusetts and founder of Collaborative Healthcare Strategies, is among the post-discharge skeptics. She agrees with Dr. Williams that the post-discharge concept is more of a temporary fix to the long-term issues in primary care. “I think the idea is getting more play than actual activity out there right now,” she says. “We need to find opportunities to manage transitions within our scope today and tomorrow while strategically looking at where we want to be in five years [as hospitals and health systems].”

Dr. Boutwell says she’s experienced the frustration of trying to make follow-up appointments with physicians who don’t have any open slots for hospitalized patients awaiting discharge. “We think of follow up as physician-led, but there are alternatives and physician extenders,” she says. “It is well-documented that our healthcare system underuses home health care and other services that might be helpful. We forget how many other opportunities there are in our communities to get another clinician to touch the patient.”

Hospitalists, as key players in the healthcare system, can speak out in support of strengthening primary-care networks and building more collaborative relationships with PCPs, according to Dr. Williams. “If you’re going to set up an outpatient clinic, ideally, have it staffed by PCPs who can funnel the patients into primary-care networks. If that’s not feasible, then hospitalists should proceed with caution, since this approach begins to take them out of their scope of practice,” he says.

With 13 years of experience in urban hospital settings, Dr. Williams is familiar with the dangers unassigned patients present at discharge. “But I don’t know that we’ve yet optimized the hospital discharge process at any hospital in the United States,” he says.

That said, Dr. Williams knows his hospital in downtown Chicago is now working to establish a post-discharge clinic. It will be staffed by PCPs and will target patients who don’t have a PCP, are on Medicaid, or lack insurance.

“Where it starts to make me uncomfortable,” Dr. Williams says, “is what happens when you follow patients out into the outpatient setting?

It’s hard to do just one visit and draw the line. Yes, you may prevent a readmission, but the patient is still left with chronic illness and the need for primary care.”

Larry Beresford is a freelance writer based in Oakland, Calif.

What Does the Research Say?

Listen to Dr. Doctoroff

Post-discharge clinic advocates acknowledge that the research documenting outcomes from such clinics is scarce. A recent study from Northwestern University looked at 12 distinct care-transitions activities and their effect on readmission rates.² Post-discharge clinics were not studied as a separate category, although they fit into the category of physician continuity across inpatient and outpatient settings.

“There’s definitely a hole in the literature regarding post-discharge care,” says lead author Luke Hansen, MD, MHS. The authors found that “no single intervention implemented alone was regularly associated with reduced risk for 30-day rehospitalizations.”

On the other hand, Misky et al found that discharged patients who lacked timely follow-up (within four weeks of discharge) were 10 times more likely to be readmitted than those who got the follow-up.³

Medical teams from around the world, including in Canada, the United Kingdom, Israel, and Australia, are studying readmission rates and care-transitions strategies. A study by physicians at National Taiwan University Hospital in Taipei describes its integrated transitional care to address post-discharge discontinuities and prevent rehospitalizations, including telephonic monitoring, hotline counseling, and referral to a hospital-run post-discharge clinic located within a hospitalist-managed ward.4 “Patients are treated primarily by the hospitalists who are familiar with them,” in a clinic open from 8 a.m. to 9 p.m., lead author Chin-Chung Shu, MD, wrote in an email. The clinic sees 15 to 30 patients per month; 80% of them are discharged patients without a PCP.

“We typically see patients one or two times in 30 days and then refer them to a suitable physician,” Dr. Shu says. In his study, patients who received post-discharge transitional care, including the post-discharge clinic, had lower rates of readmission and death within 30 days, 15% compared with 25% for a control group.

References

1. Goodman, DC, Fisher ES, Chang C. After Hospitalization: A Dartmouth Atlas Report on Post-Acute Care for Medicare Beneficiaries. Dartmouth Atlas website. Available at: www.dartmouthatlas.org/downloads/reports/Post_discharge_events_092811.pdf. Accessed Nov. 3, 2011.
2. Hansen LO, Young RS, Hinami K, Leung A, Williams MV. Interventions to reduce 3-day rehospitalization: A systematic review. Ann Int Med. 2011;155(8): 520-528.
3. Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: Examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397.
4. Shu CC, Hsu NC, Lin YF, et al. Integrated post-discharge transitional care in Taiwan. BMC Medicine website. Available at: www.biomedcentral.com/1741-7015/9/96. Accessed Nov. 1, 2011.

The hospitalist concept was established on the foundation of timely, informative handoffs to primary-care physicians (PCPs) once a patient’s hospital stay is complete. With sicker patients and shorter hospital stays, pending test results, and complex post-discharge medication regimens to sort out, this handoff is crucial to successful discharges. But what if a discharged patient can’t get in to see the PCP, or has no established PCP?

Recent research on hospital readmissions by the Dartmouth Atlas Project found that only 42% of hospitalized Medicare patients had any contact with a primary-care clinician within 14 days of discharge.¹ For patients with ongoing medical needs, such missed connections are a major contributor to hospital readmissions, and thus a target for hospitals and HM groups wanting to control their readmission rates before Medicare imposes reimbursement penalties starting in October 2012 (see “Value-Based Purchasing Raises the Stakes,” May 2011, p. 1).

One proposed solution is the post-discharge clinic, typically located on or near a hospital’s campus and staffed by hospitalists, PCPs, or advanced-practice nurses. The patient can be seen once or a few times in the post-discharge clinic to make sure that health education started in the hospital is understood and followed, and that prescriptions ordered in the hospital are being taken on schedule.

Mark V. Williams, MD, FACP, FHM, professor and chief of the division of hospital medicine at Northwestern University’s Feinberg School of Medicine in Chicago, describes hospitalist-led post-discharge clinics as “Band-Aids for an inadequate primary-care system.” What would be better, he says, is focusing on the underlying problem and working to improve post-discharge access to primary care. Dr. Williams acknowledges, however, that sometimes a patch is needed to stanch the blood flow—e.g., to better manage care transitions—while waiting on healthcare reform and medical homes to improve care coordination throughout the system.

Working in a post-discharge clinic might seem like “a stretch for many hospitalists, especially those who chose this field because they didn’t want to do outpatient medicine,” says Lauren Doctoroff, MD, a hospitalist who directs a post-discharge clinic at Beth Israel Deaconess Medical Center (BIDMC) in Boston. “But there are times when it may be appropriate for hospital-based doctors to extend their responsibility out of the hospital.”

Dr. Doctoroff also says that working in such a clinic can be practice-changing for hospitalists. “All of a sudden, you have a different view of your hospitalized patients, and you start to ask different questions while they’re in the hospital than you ever did before,” she explains.

What is a Post-Discharge Clinic?

click for large version

The post-discharge clinic, also known as a transitional-care clinic or after-care clinic, is intended to bridge medical coverage between the hospital and primary care. The clinic at BIDMC is for patients affiliated with its Health Care Associates faculty practice “discharged from either our hospital or another hospital, who need care that their PCP or specialist, because of scheduling conflicts, cannot provide within the needed time frame,” Dr. Doctoroff says.

Four hospitalists from BIDMC’s large HM group were selected to staff the clinic. The hospitalists work in one-month rotations (a total of three months on service per year), and are relieved of other responsibilities during their month in clinic. They provide five half-day clinic sessions per week, with a 40-minute-per-patient visit schedule. Thirty minutes are allotted for patients referred from the hospital’s ED who did not get admitted to the hospital but need clinical follow-up.

The clinic is based in a BIDMC-affiliated primary-care practice, “which allows us to use its administrative structure and logistical support,” Dr. Doctoroff explains. “A hospital-based administrative service helps set up outpatient visits prior to discharge using computerized physician order entry and a scheduling algorhythm.” (See Figure 1) Patients who can be seen by their PCP in a timely fashion are referred to the PCP office; if not, they are scheduled in the post-discharge clinic. “That helps preserve the PCP relationship, which I think is paramount,” she says.

The first two years were spent getting the clinic established, but in the near future, BIDMC will start measuring such outcomes as access to care and quality. “But not necessarily readmission rates,” Dr. Doctoroff adds. “I know many people think of post-discharge clinics in the context of preventing readmissions, although we don’t have the data yet to fully support that. In fact, some readmissions may result from seeing a doctor. If you get a closer look at some patients after discharge and they are doing badly, they are more likely to be readmitted than if they had just stayed home.” In such cases, readmission could actually be a better outcome for the patient, she notes.

Dr. Doctoroff describes a typical user of her post-discharge clinic as a non-English-speaking patient who was discharged from the hospital with severe back pain from a herniated disk. “He came back to see me 10 days later, still barely able to walk. He hadn’t been able to fill any of the prescriptions from his hospital stay. Within two hours after I saw him, we got his meds filled and outpatient services set up,” she says. “We take care of many patients like him in the hospital with acute pain issues, whom we discharge as soon as they can walk, and later we see them limping into outpatient clinics. It makes me think differently now about how I plan their discharges.”

We do medication reconciliation, reassessments, and follow-ups with lab tests. We also try to assess who is more likely to be a no-show, and who needs more help with scheduling follow-up appointments.

—Shay Martinez, MD, hospitalist, medical director, Harborview Medical Center, Seattle

Who else needs these clinics? Dr. Doctoroff suggests two ways of looking at the question.

“Even for a simple patient admitted to the hospital, that can represent a significant change in the medical picture—a sort of sentinel event. In the discharge clinic, we give them an opportunity to review the hospitalization and answer their questions,” she says. “A lot of information presented to patients in the hospital is not well heard, and the initial visit may be their first time to really talk about what happened.” For other patients with conditions such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or poorly controlled diabetes, treatment guidelines might dictate a pattern for post-discharge follow-up—for example, medical visits in seven or 10 days.

In Seattle, Harborview Medical Center established its After Care Clinic, staffed by hospitalists and nurse practitioners, to provide transitional care for patients discharged from inpatient wards or the ED in need of follow-up, says medical director and hospitalist Shay Martinez, MD. A second priority is to see any CHF patient within 48 hours of discharge.

“We try to limit patients to a maximum of three visits in our clinic,” she says. “At that point, we help them get established in a medical home, either here in one of our primary-care clinics, or in one of the many excellent community clinics in the area.

“This model works well with our patient population. We actually try to do primary care on the inpatient side as well. Our hospitalists are specialized in that approach, given our patient population. We see a lot of immigrants, non-English speakers, people with low health literacy, and the homeless, many of whom lack primary care,” Dr. Martinez says. “We do medication reconciliation, reassessments, and follow-ups with lab tests. We also try to assess who is more likely to be a no-show, and who needs more help with scheduling follow-up appointments.”

Clinical coverage of post-discharge clinics varies by setting, staffing, and scope. If demand is low, hospitalists or ED physicians can be called off the floor to see patients who return to the clinic, or they could staff the clinic after their hospitalist shift ends. Post-discharge clinic staff whose schedules are light can flex into providing primary-care visits in the clinic. Post-discharge can also could be provided in conjunction with—or as an alternative to—physician house calls to patients’ homes. Some post-discharge clinics work with medical call centers or telephonic case managers; some even use telemedicine.

It also could be a growth opportunity for hospitalist practices. “It is an exciting potential role for hospitalists interested in doing a little outpatient care,” Dr. Martinez says. “This is also a good way to be a safety net for your safety-net hospital.”

continued below...

What Do PCPs Think? It May Be Harder than It Looks

Listen to Dr. Doctoroff

Although some PCPs instinctively will be suspicious of a hospitalist-run post-discharge clinic, it should be possible to clearly limit the service to short-term, immediate-post-hospital encounters focused on issues related to patients unable to get timely access to primary care, according to Dr. Doctoroff.

“I think there is a diversity of opinion by PCPs,” she says. “Some doctors really believe that it interferes with the patient-doctor relationship. But after we’ve been here for a couple of years, we’ve built up credibility with many providers.”

Charles Cutler, MD, FACP, a general internist with a practice in Norristown, Pa., and a member of the ACP’s Board of Regents, says the post-discharge clinic is “a novel idea.”

“I’d be very curious to see if this really is a way to provide better and more cost-effective care,” adds Dr. Cutler, who normally retains management of his own patients when they are hospitalized but agrees that hospitals need to find a solution for lapses in care transitions.

Even so, he says, establishing an outpatient clinic presence may be more difficult than many hospitalists appreciate. “You can’t just put a doc in a room. That physician needs equipment, scheduling, and support staff,” he says. “In our small practice, we employ one person just to ensure that each patient chart is up to date. The overhead necessary to replicate a typical medical office, even one merely providing a transition of care, could be substantial.”

Dr. Cutler emphasizes such office-based challenges as billing, which is distinctly different from hospital billing, and credentialing by insurance companies.

“There are many aspects that have to be thought through. If you see the patient, you need to make yourself available for follow-up calls, because you’ve created a relationship,” he says. “I’m a believer that hospital medicine requires a degree of specialization. But so does an office practice.”

Dr. Cutler acknowledges that some PCPs will be resentful of post-discharge clinics. “But if you don’t like a hospitalist-run discharge clinic, then you have a responsibility to rearrange your schedule to accommodate patients after their hospital discharge,” he says.

Partner with Community

Tallahassee (Fla.) Memorial Hospital (TMH) in February launched a transitional-care clinic in collaboration with faculty from Florida State University, community-based health providers, and the local Capital Health Plan. Hospitalists don’t staff the clinic, but the HM group is its major source of referrals, says Dean Watson, MD, chief medical officer at TMH. Patients can be followed for up to eight weeks, during which time they get comprehensive assessments, medication review and optimization, and referral by the clinic social worker to a PCP and to available community services.

“Three years ago, we came up with the idea for a patient population we know is at high risk for readmission. Why don’t we partner with organizations in the community, form a clinic, teach students and residents, and learn together?” Dr. Watson says. “In addition to the usual patients, TMH targets those who have been readmitted to the hospital three times or more in the past year.”

The clinic, open five days a week, is staffed by a physician, nurse practitioner, telephonic nurse, and social worker, and also has a geriatric assessment clinic.

“We set up a system to identify patients through our electronic health record, and when they come to the clinic, we focus on their social environment and other non-medical issues that might cause readmissions,” he says. The clinic has a pharmacy and funds to support medications for patients without insurance. “In our first six months, we reduced emergency room visits and readmissions for these patients by 68 percent.”

One key partner, Capital Health Plan, bought and refurbished a building, and made it available for the clinic at no cost. Capital’s motivation, says Tom Glennon, a senior vice president for the plan, is its commitment to the community and to community service.

“We’re a nonprofit HMO. We’re focused on what we can do to serve the community, and we’re looking at this as a way for the hospital to have fewer costly, unreimbursed bouncebacks,” Glennon says. “That’s a win-win for all of us.”

Most of the patients who use the clinic are not members of Capital Health Plan, Glennon adds. “If we see CHP members turning up at the transitions clinic, then we have a problem—a breakdown in our case management,” he explains. “Our goal is to have our members taken care of by primary-care providers.”

Hard Data? Not So Fast

How many post-discharge clinics are in operation today is not known. Fundamental financial data, too, are limited, but some say it is unlikely a post-discharge clinic will cover operating expenses from billing revenues alone.

Thus, such clinics will require funding from the hospital, HM group, health system, or health plans, based on the benefits the clinic provides to discharged patients and the impact on 30-day readmissions (for more about the logistical challenges post-discharge clinics present, see “What Do PCPs Think?”).

Some also suggest that many of the post-discharge clinics now in operation are too new to have demonstrated financial impact or return on investment. “We have not yet been asked to show our financial viability,” Dr. Doctoroff says. “I think the clinic leadership thinks we are fulfilling other goals for now, such as creating easier access for their patients after discharge.”

Amy Boutwell, MD, MPP, a hospitalist at Newton Wellesley Hospital in Massachusetts and founder of Collaborative Healthcare Strategies, is among the post-discharge skeptics. She agrees with Dr. Williams that the post-discharge concept is more of a temporary fix to the long-term issues in primary care. “I think the idea is getting more play than actual activity out there right now,” she says. “We need to find opportunities to manage transitions within our scope today and tomorrow while strategically looking at where we want to be in five years [as hospitals and health systems].”

Dr. Boutwell says she’s experienced the frustration of trying to make follow-up appointments with physicians who don’t have any open slots for hospitalized patients awaiting discharge. “We think of follow up as physician-led, but there are alternatives and physician extenders,” she says. “It is well-documented that our healthcare system underuses home health care and other services that might be helpful. We forget how many other opportunities there are in our communities to get another clinician to touch the patient.”

Hospitalists, as key players in the healthcare system, can speak out in support of strengthening primary-care networks and building more collaborative relationships with PCPs, according to Dr. Williams. “If you’re going to set up an outpatient clinic, ideally, have it staffed by PCPs who can funnel the patients into primary-care networks. If that’s not feasible, then hospitalists should proceed with caution, since this approach begins to take them out of their scope of practice,” he says.

With 13 years of experience in urban hospital settings, Dr. Williams is familiar with the dangers unassigned patients present at discharge. “But I don’t know that we’ve yet optimized the hospital discharge process at any hospital in the United States,” he says.

That said, Dr. Williams knows his hospital in downtown Chicago is now working to establish a post-discharge clinic. It will be staffed by PCPs and will target patients who don’t have a PCP, are on Medicaid, or lack insurance.

“Where it starts to make me uncomfortable,” Dr. Williams says, “is what happens when you follow patients out into the outpatient setting?

It’s hard to do just one visit and draw the line. Yes, you may prevent a readmission, but the patient is still left with chronic illness and the need for primary care.”

Larry Beresford is a freelance writer based in Oakland, Calif.

What Does the Research Say?

Listen to Dr. Doctoroff

Post-discharge clinic advocates acknowledge that the research documenting outcomes from such clinics is scarce. A recent study from Northwestern University looked at 12 distinct care-transitions activities and their effect on readmission rates.² Post-discharge clinics were not studied as a separate category, although they fit into the category of physician continuity across inpatient and outpatient settings.

“There’s definitely a hole in the literature regarding post-discharge care,” says lead author Luke Hansen, MD, MHS. The authors found that “no single intervention implemented alone was regularly associated with reduced risk for 30-day rehospitalizations.”

On the other hand, Misky et al found that discharged patients who lacked timely follow-up (within four weeks of discharge) were 10 times more likely to be readmitted than those who got the follow-up.³

Medical teams from around the world, including in Canada, the United Kingdom, Israel, and Australia, are studying readmission rates and care-transitions strategies. A study by physicians at National Taiwan University Hospital in Taipei describes its integrated transitional care to address post-discharge discontinuities and prevent rehospitalizations, including telephonic monitoring, hotline counseling, and referral to a hospital-run post-discharge clinic located within a hospitalist-managed ward.4 “Patients are treated primarily by the hospitalists who are familiar with them,” in a clinic open from 8 a.m. to 9 p.m., lead author Chin-Chung Shu, MD, wrote in an email. The clinic sees 15 to 30 patients per month; 80% of them are discharged patients without a PCP.

“We typically see patients one or two times in 30 days and then refer them to a suitable physician,” Dr. Shu says. In his study, patients who received post-discharge transitional care, including the post-discharge clinic, had lower rates of readmission and death within 30 days, 15% compared with 25% for a control group.

References

1. Goodman, DC, Fisher ES, Chang C. After Hospitalization: A Dartmouth Atlas Report on Post-Acute Care for Medicare Beneficiaries. Dartmouth Atlas website. Available at: www.dartmouthatlas.org/downloads/reports/Post_discharge_events_092811.pdf. Accessed Nov. 3, 2011.
2. Hansen LO, Young RS, Hinami K, Leung A, Williams MV. Interventions to reduce 3-day rehospitalization: A systematic review. Ann Int Med. 2011;155(8): 520-528.
3. Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: Examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397.
4. Shu CC, Hsu NC, Lin YF, et al. Integrated post-discharge transitional care in Taiwan. BMC Medicine website. Available at: www.biomedcentral.com/1741-7015/9/96. Accessed Nov. 1, 2011.

The hospitalist concept was established on the foundation of timely, informative handoffs to primary-care physicians (PCPs) once a patient’s hospital stay is complete. With sicker patients and shorter hospital stays, pending test results, and complex post-discharge medication regimens to sort out, this handoff is crucial to successful discharges. But what if a discharged patient can’t get in to see the PCP, or has no established PCP?

Recent research on hospital readmissions by the Dartmouth Atlas Project found that only 42% of hospitalized Medicare patients had any contact with a primary-care clinician within 14 days of discharge.¹ For patients with ongoing medical needs, such missed connections are a major contributor to hospital readmissions, and thus a target for hospitals and HM groups wanting to control their readmission rates before Medicare imposes reimbursement penalties starting in October 2012 (see “Value-Based Purchasing Raises the Stakes,” May 2011, p. 1).

One proposed solution is the post-discharge clinic, typically located on or near a hospital’s campus and staffed by hospitalists, PCPs, or advanced-practice nurses. The patient can be seen once or a few times in the post-discharge clinic to make sure that health education started in the hospital is understood and followed, and that prescriptions ordered in the hospital are being taken on schedule.

Mark V. Williams, MD, FACP, FHM, professor and chief of the division of hospital medicine at Northwestern University’s Feinberg School of Medicine in Chicago, describes hospitalist-led post-discharge clinics as “Band-Aids for an inadequate primary-care system.” What would be better, he says, is focusing on the underlying problem and working to improve post-discharge access to primary care. Dr. Williams acknowledges, however, that sometimes a patch is needed to stanch the blood flow—e.g., to better manage care transitions—while waiting on healthcare reform and medical homes to improve care coordination throughout the system.

Working in a post-discharge clinic might seem like “a stretch for many hospitalists, especially those who chose this field because they didn’t want to do outpatient medicine,” says Lauren Doctoroff, MD, a hospitalist who directs a post-discharge clinic at Beth Israel Deaconess Medical Center (BIDMC) in Boston. “But there are times when it may be appropriate for hospital-based doctors to extend their responsibility out of the hospital.”

Dr. Doctoroff also says that working in such a clinic can be practice-changing for hospitalists. “All of a sudden, you have a different view of your hospitalized patients, and you start to ask different questions while they’re in the hospital than you ever did before,” she explains.

What is a Post-Discharge Clinic?

click for large version

The post-discharge clinic, also known as a transitional-care clinic or after-care clinic, is intended to bridge medical coverage between the hospital and primary care. The clinic at BIDMC is for patients affiliated with its Health Care Associates faculty practice “discharged from either our hospital or another hospital, who need care that their PCP or specialist, because of scheduling conflicts, cannot provide within the needed time frame,” Dr. Doctoroff says.

Four hospitalists from BIDMC’s large HM group were selected to staff the clinic. The hospitalists work in one-month rotations (a total of three months on service per year), and are relieved of other responsibilities during their month in clinic. They provide five half-day clinic sessions per week, with a 40-minute-per-patient visit schedule. Thirty minutes are allotted for patients referred from the hospital’s ED who did not get admitted to the hospital but need clinical follow-up.

The clinic is based in a BIDMC-affiliated primary-care practice, “which allows us to use its administrative structure and logistical support,” Dr. Doctoroff explains. “A hospital-based administrative service helps set up outpatient visits prior to discharge using computerized physician order entry and a scheduling algorhythm.” (See Figure 1) Patients who can be seen by their PCP in a timely fashion are referred to the PCP office; if not, they are scheduled in the post-discharge clinic. “That helps preserve the PCP relationship, which I think is paramount,” she says.

The first two years were spent getting the clinic established, but in the near future, BIDMC will start measuring such outcomes as access to care and quality. “But not necessarily readmission rates,” Dr. Doctoroff adds. “I know many people think of post-discharge clinics in the context of preventing readmissions, although we don’t have the data yet to fully support that. In fact, some readmissions may result from seeing a doctor. If you get a closer look at some patients after discharge and they are doing badly, they are more likely to be readmitted than if they had just stayed home.” In such cases, readmission could actually be a better outcome for the patient, she notes.

Dr. Doctoroff describes a typical user of her post-discharge clinic as a non-English-speaking patient who was discharged from the hospital with severe back pain from a herniated disk. “He came back to see me 10 days later, still barely able to walk. He hadn’t been able to fill any of the prescriptions from his hospital stay. Within two hours after I saw him, we got his meds filled and outpatient services set up,” she says. “We take care of many patients like him in the hospital with acute pain issues, whom we discharge as soon as they can walk, and later we see them limping into outpatient clinics. It makes me think differently now about how I plan their discharges.”

We do medication reconciliation, reassessments, and follow-ups with lab tests. We also try to assess who is more likely to be a no-show, and who needs more help with scheduling follow-up appointments.

—Shay Martinez, MD, hospitalist, medical director, Harborview Medical Center, Seattle

Who else needs these clinics? Dr. Doctoroff suggests two ways of looking at the question.

“Even for a simple patient admitted to the hospital, that can represent a significant change in the medical picture—a sort of sentinel event. In the discharge clinic, we give them an opportunity to review the hospitalization and answer their questions,” she says. “A lot of information presented to patients in the hospital is not well heard, and the initial visit may be their first time to really talk about what happened.” For other patients with conditions such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or poorly controlled diabetes, treatment guidelines might dictate a pattern for post-discharge follow-up—for example, medical visits in seven or 10 days.

In Seattle, Harborview Medical Center established its After Care Clinic, staffed by hospitalists and nurse practitioners, to provide transitional care for patients discharged from inpatient wards or the ED in need of follow-up, says medical director and hospitalist Shay Martinez, MD. A second priority is to see any CHF patient within 48 hours of discharge.

“We try to limit patients to a maximum of three visits in our clinic,” she says. “At that point, we help them get established in a medical home, either here in one of our primary-care clinics, or in one of the many excellent community clinics in the area.

“This model works well with our patient population. We actually try to do primary care on the inpatient side as well. Our hospitalists are specialized in that approach, given our patient population. We see a lot of immigrants, non-English speakers, people with low health literacy, and the homeless, many of whom lack primary care,” Dr. Martinez says. “We do medication reconciliation, reassessments, and follow-ups with lab tests. We also try to assess who is more likely to be a no-show, and who needs more help with scheduling follow-up appointments.”

Clinical coverage of post-discharge clinics varies by setting, staffing, and scope. If demand is low, hospitalists or ED physicians can be called off the floor to see patients who return to the clinic, or they could staff the clinic after their hospitalist shift ends. Post-discharge clinic staff whose schedules are light can flex into providing primary-care visits in the clinic. Post-discharge can also could be provided in conjunction with—or as an alternative to—physician house calls to patients’ homes. Some post-discharge clinics work with medical call centers or telephonic case managers; some even use telemedicine.

It also could be a growth opportunity for hospitalist practices. “It is an exciting potential role for hospitalists interested in doing a little outpatient care,” Dr. Martinez says. “This is also a good way to be a safety net for your safety-net hospital.”

continued below...

What Do PCPs Think? It May Be Harder than It Looks

Listen to Dr. Doctoroff

Although some PCPs instinctively will be suspicious of a hospitalist-run post-discharge clinic, it should be possible to clearly limit the service to short-term, immediate-post-hospital encounters focused on issues related to patients unable to get timely access to primary care, according to Dr. Doctoroff.

“I think there is a diversity of opinion by PCPs,” she says. “Some doctors really believe that it interferes with the patient-doctor relationship. But after we’ve been here for a couple of years, we’ve built up credibility with many providers.”

Charles Cutler, MD, FACP, a general internist with a practice in Norristown, Pa., and a member of the ACP’s Board of Regents, says the post-discharge clinic is “a novel idea.”

“I’d be very curious to see if this really is a way to provide better and more cost-effective care,” adds Dr. Cutler, who normally retains management of his own patients when they are hospitalized but agrees that hospitals need to find a solution for lapses in care transitions.

Even so, he says, establishing an outpatient clinic presence may be more difficult than many hospitalists appreciate. “You can’t just put a doc in a room. That physician needs equipment, scheduling, and support staff,” he says. “In our small practice, we employ one person just to ensure that each patient chart is up to date. The overhead necessary to replicate a typical medical office, even one merely providing a transition of care, could be substantial.”

Dr. Cutler emphasizes such office-based challenges as billing, which is distinctly different from hospital billing, and credentialing by insurance companies.

“There are many aspects that have to be thought through. If you see the patient, you need to make yourself available for follow-up calls, because you’ve created a relationship,” he says. “I’m a believer that hospital medicine requires a degree of specialization. But so does an office practice.”

Dr. Cutler acknowledges that some PCPs will be resentful of post-discharge clinics. “But if you don’t like a hospitalist-run discharge clinic, then you have a responsibility to rearrange your schedule to accommodate patients after their hospital discharge,” he says.

Partner with Community

Tallahassee (Fla.) Memorial Hospital (TMH) in February launched a transitional-care clinic in collaboration with faculty from Florida State University, community-based health providers, and the local Capital Health Plan. Hospitalists don’t staff the clinic, but the HM group is its major source of referrals, says Dean Watson, MD, chief medical officer at TMH. Patients can be followed for up to eight weeks, during which time they get comprehensive assessments, medication review and optimization, and referral by the clinic social worker to a PCP and to available community services.

“Three years ago, we came up with the idea for a patient population we know is at high risk for readmission. Why don’t we partner with organizations in the community, form a clinic, teach students and residents, and learn together?” Dr. Watson says. “In addition to the usual patients, TMH targets those who have been readmitted to the hospital three times or more in the past year.”

The clinic, open five days a week, is staffed by a physician, nurse practitioner, telephonic nurse, and social worker, and also has a geriatric assessment clinic.

“We set up a system to identify patients through our electronic health record, and when they come to the clinic, we focus on their social environment and other non-medical issues that might cause readmissions,” he says. The clinic has a pharmacy and funds to support medications for patients without insurance. “In our first six months, we reduced emergency room visits and readmissions for these patients by 68 percent.”

One key partner, Capital Health Plan, bought and refurbished a building, and made it available for the clinic at no cost. Capital’s motivation, says Tom Glennon, a senior vice president for the plan, is its commitment to the community and to community service.

“We’re a nonprofit HMO. We’re focused on what we can do to serve the community, and we’re looking at this as a way for the hospital to have fewer costly, unreimbursed bouncebacks,” Glennon says. “That’s a win-win for all of us.”

Most of the patients who use the clinic are not members of Capital Health Plan, Glennon adds. “If we see CHP members turning up at the transitions clinic, then we have a problem—a breakdown in our case management,” he explains. “Our goal is to have our members taken care of by primary-care providers.”

Hard Data? Not So Fast

How many post-discharge clinics are in operation today is not known. Fundamental financial data, too, are limited, but some say it is unlikely a post-discharge clinic will cover operating expenses from billing revenues alone.

Thus, such clinics will require funding from the hospital, HM group, health system, or health plans, based on the benefits the clinic provides to discharged patients and the impact on 30-day readmissions (for more about the logistical challenges post-discharge clinics present, see “What Do PCPs Think?”).

Some also suggest that many of the post-discharge clinics now in operation are too new to have demonstrated financial impact or return on investment. “We have not yet been asked to show our financial viability,” Dr. Doctoroff says. “I think the clinic leadership thinks we are fulfilling other goals for now, such as creating easier access for their patients after discharge.”

Amy Boutwell, MD, MPP, a hospitalist at Newton Wellesley Hospital in Massachusetts and founder of Collaborative Healthcare Strategies, is among the post-discharge skeptics. She agrees with Dr. Williams that the post-discharge concept is more of a temporary fix to the long-term issues in primary care. “I think the idea is getting more play than actual activity out there right now,” she says. “We need to find opportunities to manage transitions within our scope today and tomorrow while strategically looking at where we want to be in five years [as hospitals and health systems].”

Dr. Boutwell says she’s experienced the frustration of trying to make follow-up appointments with physicians who don’t have any open slots for hospitalized patients awaiting discharge. “We think of follow up as physician-led, but there are alternatives and physician extenders,” she says. “It is well-documented that our healthcare system underuses home health care and other services that might be helpful. We forget how many other opportunities there are in our communities to get another clinician to touch the patient.”

Hospitalists, as key players in the healthcare system, can speak out in support of strengthening primary-care networks and building more collaborative relationships with PCPs, according to Dr. Williams. “If you’re going to set up an outpatient clinic, ideally, have it staffed by PCPs who can funnel the patients into primary-care networks. If that’s not feasible, then hospitalists should proceed with caution, since this approach begins to take them out of their scope of practice,” he says.

With 13 years of experience in urban hospital settings, Dr. Williams is familiar with the dangers unassigned patients present at discharge. “But I don’t know that we’ve yet optimized the hospital discharge process at any hospital in the United States,” he says.

That said, Dr. Williams knows his hospital in downtown Chicago is now working to establish a post-discharge clinic. It will be staffed by PCPs and will target patients who don’t have a PCP, are on Medicaid, or lack insurance.

“Where it starts to make me uncomfortable,” Dr. Williams says, “is what happens when you follow patients out into the outpatient setting?

It’s hard to do just one visit and draw the line. Yes, you may prevent a readmission, but the patient is still left with chronic illness and the need for primary care.”

Larry Beresford is a freelance writer based in Oakland, Calif.

What Does the Research Say?

Listen to Dr. Doctoroff

Post-discharge clinic advocates acknowledge that the research documenting outcomes from such clinics is scarce. A recent study from Northwestern University looked at 12 distinct care-transitions activities and their effect on readmission rates.² Post-discharge clinics were not studied as a separate category, although they fit into the category of physician continuity across inpatient and outpatient settings.

“There’s definitely a hole in the literature regarding post-discharge care,” says lead author Luke Hansen, MD, MHS. The authors found that “no single intervention implemented alone was regularly associated with reduced risk for 30-day rehospitalizations.”

On the other hand, Misky et al found that discharged patients who lacked timely follow-up (within four weeks of discharge) were 10 times more likely to be readmitted than those who got the follow-up.³

Medical teams from around the world, including in Canada, the United Kingdom, Israel, and Australia, are studying readmission rates and care-transitions strategies. A study by physicians at National Taiwan University Hospital in Taipei describes its integrated transitional care to address post-discharge discontinuities and prevent rehospitalizations, including telephonic monitoring, hotline counseling, and referral to a hospital-run post-discharge clinic located within a hospitalist-managed ward.4 “Patients are treated primarily by the hospitalists who are familiar with them,” in a clinic open from 8 a.m. to 9 p.m., lead author Chin-Chung Shu, MD, wrote in an email. The clinic sees 15 to 30 patients per month; 80% of them are discharged patients without a PCP.

“We typically see patients one or two times in 30 days and then refer them to a suitable physician,” Dr. Shu says. In his study, patients who received post-discharge transitional care, including the post-discharge clinic, had lower rates of readmission and death within 30 days, 15% compared with 25% for a control group.

References

1. Goodman, DC, Fisher ES, Chang C. After Hospitalization: A Dartmouth Atlas Report on Post-Acute Care for Medicare Beneficiaries. Dartmouth Atlas website. Available at: www.dartmouthatlas.org/downloads/reports/Post_discharge_events_092811.pdf. Accessed Nov. 3, 2011.
2. Hansen LO, Young RS, Hinami K, Leung A, Williams MV. Interventions to reduce 3-day rehospitalization: A systematic review. Ann Int Med. 2011;155(8): 520-528.
3. Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: Examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397.
4. Shu CC, Hsu NC, Lin YF, et al. Integrated post-discharge transitional care in Taiwan. BMC Medicine website. Available at: www.biomedcentral.com/1741-7015/9/96. Accessed Nov. 1, 2011.

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Case

A 63-year-old man with severe chronic obstructive pulmonary disease (COPD) presents with one week of increasing sputum, cough, and dyspnea. His respiratory rate is 26/minute and oxygen saturation is 86% on room air (RA). He is lethargic and appears mildly uncomfortable, but he responds appropriately to questions in three- to four-word sentences. He is tachypneic with accessory muscle use and has diffuse wheezes throughout his bilateral lung fields. His initial room air arterial blood gas (ABG) is 7.32/68/86/32. Chest radiograph is notable for flattened hemidiaphragms without focal opacity. The patient is placed on oxygen and receives prednisone with nebulized albuterol and ipratropium, but his dyspnea and tachypnea persist. Due to his respiratory distress, bilevel positive airway pressure (BiPAP) is considered.

What are the clinical indications for noninvasive positive pressure ventilation (NPPV)?

Overview

NPPV assists ventilation by delivering positive expiratory and/or inspiratory pressure without the use of an endotracheal tube. Theoretically, NPPV is a preferred method of ventilation as it may eliminate the need for endotracheal intubation and its associated morbidity and mortality, including airway trauma, loss of airway defense mechanisms (ventilator-associated pneumonia), mechanical ventilation (barotrauma), and disruption of speech and swallowing.¹

NPPV is generally delivered via full-face mask or nasal mask. Nasal mask is often preferred for patient comfort, though air leaks occur with mouth breathing. There is no difference between nasal and full-face masks in outcomes including intubation rates and mortality.^2,3,4 NPPV can be delivered via a portable or standard ventilator using the same modes available for endotracheal intubation, though pressure-cycled ventilators utilizing continuous positive airway pressure (CPAP) and BiPAP are most common. CPAP delivers air at a continuous fixed pressure throughout the respiratory cycle. BiPAP delivers positive pressure at alternating levels—higher for inspiration and lower for expiration. Guidelines suggest choosing a mode based on the etiology and pathophysiology of the respiratory failure and leveraging local comfort and expertise.^2,3

In general, good candidates for NPPV display signs of tachypnea and dyspnea due to hypoxic or hypercapnic respiratory failure but are hemodynamically stable, without excessive secretions, and can protect their airway and achieve a proper seal with the mask.³ Difficulty may arise due to patient intolerance, claustrophobia, gastric distention, and poor fit that leads to air leak or skin erosion. With initiation of NPPV, patients should be followed in a care setting with the capacity for frequent monitoring and, if needed, quick access to invasive airway management. Monitoring should include patient comfort and ability to tolerate the device, vital signs, breathing pattern, oxygen saturation, ABG, and mental status. This initial evaluation may help predict the success of NPPV (see Table 2). Appropriately chosen candidates who do well with NPPV often demonstrate respiratory turnaround in a relatively brief interval^.2,3

click for large version

Review of the Data

NPPV is increasingly utilized in a variety of clinical situations. In 2000, the American Thoracic Society published consensus guidelines on the use of NPPV in acute respiratory failure.² More recently, the Canadian Medical Association developed clinical guidelines for the use of NPPV in the acute-care setting.⁴ Clinical scenarios in which there is evidence for the efficacy of NPPV include severe exacerbations of COPD, cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates, and hypoxia; it can also be used as a bridge to extubation in COPD patients.^1-4

Acute exacerbation of COPD. Several randomized controlled trials (RCT) and meta-analyses have assessed the potential benefits of NPPV in patients with acute exacerbations of COPD. In COPD, NPPV improves gas exchange and facilitates respiratory muscle rest to decrease the work of breathing, which allows for respiratory recovery and time to effectiveness of standard therapies.⁵ Multiple trials have demonstrated that the addition of NPPV to usual care decreases intubation and mortality rates, as well as hospital lengths of stay (LOS).^5-8

A Cochrane review of eight RCTs comparing NPPV with usual care noted a greater than 50% reduction in risk of intubation, and a number needed to treat (NNT) of eight patients to prevent one death.⁵ Quon and colleagues also compared NPPV to usual care in a meta-analysis of 14 trials.⁶ Eleven of these trials evaluated hospital mortality, which was decreased by 55% in patients receiving NPPV. Twelve trials assessed need for intubation, which decreased by 65%. In these trials, BiPAP was the most commonly used modality (see Table 3, for a comparison of NPPV modalities). Study patients had an average pH of 7.31 with an average PaCO2 of 68 mmHg. It was noted that the beneficial effects of NPPV increased as pH decreased. An earlier meta-analysis from Keenan and colleagues supported this notion, noting that the subgroup of patients with pH <7.3 benefited most in terms of decreased rates of intubation, hospital LOS, and hospital mortality.7 In this 2003 study, patients with relatively mild exacerbations of COPD did not benefit from the addition of NPPV to usual care. Based on the amount of positive evidence, NPPV is recommended in patients experiencing severe exacerbations of COPD as evidenced by a pH <7.35 and relative hypercarbia.^1,2,4,7

click for large version

Cardiogenic pulmonary edema. In patients with acute cardiogenic pulmonary edema, NPPV has been found to be beneficial, decreasing mortality, rates of intubation, and hospital LOS. Physiologically, NPPV augments cardiac output, improves respiratory mechanics, and decreases afterload.10 Cardiogenic edema is variably defined and has a number of causes elucidated in an analysis of 11 RCTs conducted by Masip and colleagues. These causes included acute coronary syndrome (31%), hypertension (27%), congestive heart failure (14%), and a combination of respiratory infection, arrhythmia, volume overload, and treatment noncompliance (28%).⁹ In this analysis, CPAP and BiPAP demonstrated a combined 43% reduction in mortality and a 57% reduction in intubation. More recently, Peter and colleagues described a statistically significant reduction in hospital mortality and the need for intubation with CPAP, while BiPAP only demonstrated a statistically significant decrease in need for intubation.¹⁰ Thus, there appears to be some evidence that CPAP is the preferred NPPV mode in patients with acute cardiogenic pulmonary edema. Despite inclusion of a recent, large RCT showing no benefit of NPPV versus usual care in cardiogenic pulmonary edema, the overall positive effect of NPPV persisted, particularly when the cause of pulmonary edema was acute coronary syndrome.¹¹

Weaning after intubation. NPPV has been evaluated as a method to facilitate early extubation, as a measure to prevent extubation failure, and as a treatment modality for respiratory failure following extubation, with mixed results.^12,13 In 1998, a small trial compared the use of NPPV in COPD patients to facilitate early extubation with a standard weaning protocol. In this population, early NPPV resulted in better weaning rates with shorter times of mechanical ventilation (10 vs. 16 days), fewer days in the ICU, and improved 60-day survival rates (92% vs. 72%).^3,14 In another RCT not limited to COPD patients, Grault and colleagues found that NPPV reduced the duration of intubation (4.5 vs. 7.6 days) but was not associated with benefits in ICU length of stay or survival previously described.^3,15 Thus, though NPPV may be beneficial in facilitating early extubation in COPD patients, it is not recommended in other patient populations.⁴

NPPV has also been evaluated as a measure to prevent respiratory failure in patients at high risk for extubation failure. When applied immediately after extubation in patients with COPD and obesity, NPPV reduced reintubation rates and ICU mortality.^3,4 In 2004, Esteban and colleagues examined NPPV in patients who had respiratory failure following extubation. In this setting, NPPV was ineffective at preventing reintubation and had no survival benefit.

In summary, NPPV may facilitate early extubation and prevent extubation failure in appropriate patients, such as those with COPD, but is unlikely to be beneficial and is not recommended in patients with existing respiratory failure after extubation.^4,15

Immunosuppressed patients. A 2001 single-center, randomized-controlled trial by Holbert and colleagues demonstrated decreased intubation rates and mortality with the application of NPPV in immunosuppressed patients with hypoxemic respiratory failure, fever, and pulmonary infiltrates.¹⁶

In this study, immunosuppression occurred most commonly as a result of malignancy. In the group receiving NPPV alternating with oxygen (at least 45 minutes of NPPV alternated every three hours with periods of spontaneous breathing), the rate of subsequent intubation decreased to 46%, compared with 77% in those receiving oxygen alone. The mortality rate was 38% in the NPPV group, as compared with 69% in the standard treatment group.

Though the outcomes in immunocompromised patients with hypoxemia, fever, and pulmonary infiltrates were very poor (38% mortality even with NPPV), this small study and recent guidelines suggest a trial of NPPV in this population.^4,16

Other indications. NPPV has been applied in multiple other clinical scenarios, including exacerbation of asthma, community-acquired pneumonia, acute lung injury, and bronchoscopy in hypoxemic patients. It has also been evaluated in the postsurgical period and in chest trauma. There are mixed and less robust data in these various applications, and larger controlled trials are lacking.

In asthma exacerbation, NPPV may improve dyspnea, but data regarding outcomes (intubation, mortality) are lacking. A 2005 Cochrane review concluded that data remain controversial due to insufficient evidence, and guidelines make no recommendations concerning NPPV in asthma exacerbation.^4,17 Similarly, in community-acquired pneumonia without prior history of COPD, there is no major role for NPPV.^1,3,4 Limited data suggest that NPPV lacks efficacy in preventing post-surgical respiratory failure, though it may be useful in treating existing respiratory failure or preventing intubation in patients following lung resection or abdominal surgery.^1,4 In hypoxemic patients undergoing bronchoscopy, NPPV may improve oxygenation (lower respiratory rates and improved PaO2 to FiO2 ratios, compared with oxygen alone) as well as hemodynamics (minimizing the drop in mean arterial pressure). However, outcome data are lacking and the data set is small.^4,18 In acute lung injury/acute respiratory distress syndrome, data are also limited, but NPPV appears to have a high failure rate and confers little benefit.^1,4

Back to the Case

The patient was admitted to the hospital and placed on BiPAP for approximately 1.5 hours. The patient’s respiratory rate improved to 20/minute and he appeared increasingly comfortable and alert. A repeat ABG revealed improved hypercarbia and acidosis. He was continued on steroids and antibiotics and eventually was weaned from BiPAP and discharged home.

Bottom Line

NPPV is an effective method to decrease mortality, intubation rates, and duration of ICU stay in severe exacerbations of COPD, cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates, and hypoxia, and as a bridge to extubation in COPD patients.

Dr. Kraynek is an internal medicine resident in the Department of Medicine at the University of Washington School of Medicine in Seattle. Dr. Best is assistant professor of medicine in the Division of General Internal Medicine at the University of Washington School of Medicine.

References

1. Ambrosino N, Vagheggini G. Noninvasive positive pressure ventilation in the acute care setting: where are we? Euro Resp J. 2008;31:874-856.
2. American Thoracic Society. International Consensus Conferences in Intensive Care Medicine: Noninvasive Positive Pressure Ventilation in Acute Respiratory Failure. Am J Respir Crit Care Med. 2001;163:283-291.
3. Liesching T, Kwok H, Hill N. Acute applications of noninvasive positive pressure ventilation. Chest. 2003;124:699-713.
4. Keenan S, Sinuff T, Burns K, et al. Clinical practice guidelines for the use of noninvasive positive pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. CMAJ. 2001;183:E195-E214.
5. Lightowler J, Wedzicha J, Elliot M, Ram F. Noninvasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ. 2003;326:185.
6. Quon B, Gan W, Sin D. Contemporary management of acute exacerbations of COPD: a systematic review of the metaanalysis. Chest. 2008;133:756-766.
7. Keenan S, Sinuff T, Cook D, Hill, N. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive pressure ventilation? Ann Intern Med. 2003;138:861-870.
8. Scala R, Naldi M, Archinucci I, Conigilo G, Nava S. Noninvasive positive pressure ventilation in patients with acute exacerbations of COPD and varying levels of consciousness. Chest. 2005;128:1657-1666.
9. Masip J, Roque M, Sanchez B, Fernandez R, Subirana M, Exposito J. Noninvasive ventilation in acute cardiogenic pulmonary edema. JAMA. 2005;294:3124-3130.
10. Peter J, Moran J, Phillips-Hughes J, Graham P, Bersten A. Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-anaylsis. Lancet. 2006;367:1155-1163.
11. Weng C, Zhao Y, Liu Q, et al. Meta-analysis: noninvasive ventilation in acute cardiogenic pulmonary edema. Ann Intern Med. 2010;152:560-600.
12. Keenan S, Sinuff T, Cook D, Hill N. Does noninvasive positive pressure ventilation improve outcome in acute hypoxemic respiratory failure? A systematic review. Crit Care Med. 2004;32:2516-2523.
13. Esteban A, Frutos-Vivar F, Fergusun N, et al. Noninvasive positive pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350:2452-2460.
14. Nava S, Ambrosino N, Clinie E, et al. Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease: a randomized, controlled trial. Ann Intern Med. 1998;128:721-728.
15. Grault C, Daudenthun I, Chevron V, et al. Noninvasive ventilation as a systematic extubation and weaning technique in acute on chronic respiratory failure: a prospective, randomized controlled study. Am J Respir Crit Care Med. 1999;160:86-92.
16. Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med. 2001;344:481-487.
17. Ram FSF, Wellington SR, Rowe BH, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database of Systematic Reviews. 2005, Issue 3.
18. Antonelli M, Conti G, Rocco M, et al. Noninvasive positive pressure ventilation vs. conventional oxygen supplementation in hypoxemic patients undergoing diagnostic bronchoscopy. Chest. 2002;121:1149-1154.

click for large version

Case

A 63-year-old man with severe chronic obstructive pulmonary disease (COPD) presents with one week of increasing sputum, cough, and dyspnea. His respiratory rate is 26/minute and oxygen saturation is 86% on room air (RA). He is lethargic and appears mildly uncomfortable, but he responds appropriately to questions in three- to four-word sentences. He is tachypneic with accessory muscle use and has diffuse wheezes throughout his bilateral lung fields. His initial room air arterial blood gas (ABG) is 7.32/68/86/32. Chest radiograph is notable for flattened hemidiaphragms without focal opacity. The patient is placed on oxygen and receives prednisone with nebulized albuterol and ipratropium, but his dyspnea and tachypnea persist. Due to his respiratory distress, bilevel positive airway pressure (BiPAP) is considered.

What are the clinical indications for noninvasive positive pressure ventilation (NPPV)?

Overview

NPPV assists ventilation by delivering positive expiratory and/or inspiratory pressure without the use of an endotracheal tube. Theoretically, NPPV is a preferred method of ventilation as it may eliminate the need for endotracheal intubation and its associated morbidity and mortality, including airway trauma, loss of airway defense mechanisms (ventilator-associated pneumonia), mechanical ventilation (barotrauma), and disruption of speech and swallowing.¹

NPPV is generally delivered via full-face mask or nasal mask. Nasal mask is often preferred for patient comfort, though air leaks occur with mouth breathing. There is no difference between nasal and full-face masks in outcomes including intubation rates and mortality.^2,3,4 NPPV can be delivered via a portable or standard ventilator using the same modes available for endotracheal intubation, though pressure-cycled ventilators utilizing continuous positive airway pressure (CPAP) and BiPAP are most common. CPAP delivers air at a continuous fixed pressure throughout the respiratory cycle. BiPAP delivers positive pressure at alternating levels—higher for inspiration and lower for expiration. Guidelines suggest choosing a mode based on the etiology and pathophysiology of the respiratory failure and leveraging local comfort and expertise.^2,3

In general, good candidates for NPPV display signs of tachypnea and dyspnea due to hypoxic or hypercapnic respiratory failure but are hemodynamically stable, without excessive secretions, and can protect their airway and achieve a proper seal with the mask.³ Difficulty may arise due to patient intolerance, claustrophobia, gastric distention, and poor fit that leads to air leak or skin erosion. With initiation of NPPV, patients should be followed in a care setting with the capacity for frequent monitoring and, if needed, quick access to invasive airway management. Monitoring should include patient comfort and ability to tolerate the device, vital signs, breathing pattern, oxygen saturation, ABG, and mental status. This initial evaluation may help predict the success of NPPV (see Table 2). Appropriately chosen candidates who do well with NPPV often demonstrate respiratory turnaround in a relatively brief interval^.2,3

click for large version

Review of the Data

NPPV is increasingly utilized in a variety of clinical situations. In 2000, the American Thoracic Society published consensus guidelines on the use of NPPV in acute respiratory failure.² More recently, the Canadian Medical Association developed clinical guidelines for the use of NPPV in the acute-care setting.⁴ Clinical scenarios in which there is evidence for the efficacy of NPPV include severe exacerbations of COPD, cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates, and hypoxia; it can also be used as a bridge to extubation in COPD patients.^1-4

Acute exacerbation of COPD. Several randomized controlled trials (RCT) and meta-analyses have assessed the potential benefits of NPPV in patients with acute exacerbations of COPD. In COPD, NPPV improves gas exchange and facilitates respiratory muscle rest to decrease the work of breathing, which allows for respiratory recovery and time to effectiveness of standard therapies.⁵ Multiple trials have demonstrated that the addition of NPPV to usual care decreases intubation and mortality rates, as well as hospital lengths of stay (LOS).^5-8

A Cochrane review of eight RCTs comparing NPPV with usual care noted a greater than 50% reduction in risk of intubation, and a number needed to treat (NNT) of eight patients to prevent one death.⁵ Quon and colleagues also compared NPPV to usual care in a meta-analysis of 14 trials.⁶ Eleven of these trials evaluated hospital mortality, which was decreased by 55% in patients receiving NPPV. Twelve trials assessed need for intubation, which decreased by 65%. In these trials, BiPAP was the most commonly used modality (see Table 3, for a comparison of NPPV modalities). Study patients had an average pH of 7.31 with an average PaCO2 of 68 mmHg. It was noted that the beneficial effects of NPPV increased as pH decreased. An earlier meta-analysis from Keenan and colleagues supported this notion, noting that the subgroup of patients with pH <7.3 benefited most in terms of decreased rates of intubation, hospital LOS, and hospital mortality.7 In this 2003 study, patients with relatively mild exacerbations of COPD did not benefit from the addition of NPPV to usual care. Based on the amount of positive evidence, NPPV is recommended in patients experiencing severe exacerbations of COPD as evidenced by a pH <7.35 and relative hypercarbia.^1,2,4,7

click for large version

Cardiogenic pulmonary edema. In patients with acute cardiogenic pulmonary edema, NPPV has been found to be beneficial, decreasing mortality, rates of intubation, and hospital LOS. Physiologically, NPPV augments cardiac output, improves respiratory mechanics, and decreases afterload.10 Cardiogenic edema is variably defined and has a number of causes elucidated in an analysis of 11 RCTs conducted by Masip and colleagues. These causes included acute coronary syndrome (31%), hypertension (27%), congestive heart failure (14%), and a combination of respiratory infection, arrhythmia, volume overload, and treatment noncompliance (28%).⁹ In this analysis, CPAP and BiPAP demonstrated a combined 43% reduction in mortality and a 57% reduction in intubation. More recently, Peter and colleagues described a statistically significant reduction in hospital mortality and the need for intubation with CPAP, while BiPAP only demonstrated a statistically significant decrease in need for intubation.¹⁰ Thus, there appears to be some evidence that CPAP is the preferred NPPV mode in patients with acute cardiogenic pulmonary edema. Despite inclusion of a recent, large RCT showing no benefit of NPPV versus usual care in cardiogenic pulmonary edema, the overall positive effect of NPPV persisted, particularly when the cause of pulmonary edema was acute coronary syndrome.¹¹

Weaning after intubation. NPPV has been evaluated as a method to facilitate early extubation, as a measure to prevent extubation failure, and as a treatment modality for respiratory failure following extubation, with mixed results.^12,13 In 1998, a small trial compared the use of NPPV in COPD patients to facilitate early extubation with a standard weaning protocol. In this population, early NPPV resulted in better weaning rates with shorter times of mechanical ventilation (10 vs. 16 days), fewer days in the ICU, and improved 60-day survival rates (92% vs. 72%).^3,14 In another RCT not limited to COPD patients, Grault and colleagues found that NPPV reduced the duration of intubation (4.5 vs. 7.6 days) but was not associated with benefits in ICU length of stay or survival previously described.^3,15 Thus, though NPPV may be beneficial in facilitating early extubation in COPD patients, it is not recommended in other patient populations.⁴

NPPV has also been evaluated as a measure to prevent respiratory failure in patients at high risk for extubation failure. When applied immediately after extubation in patients with COPD and obesity, NPPV reduced reintubation rates and ICU mortality.^3,4 In 2004, Esteban and colleagues examined NPPV in patients who had respiratory failure following extubation. In this setting, NPPV was ineffective at preventing reintubation and had no survival benefit.

In summary, NPPV may facilitate early extubation and prevent extubation failure in appropriate patients, such as those with COPD, but is unlikely to be beneficial and is not recommended in patients with existing respiratory failure after extubation.^4,15

Immunosuppressed patients. A 2001 single-center, randomized-controlled trial by Holbert and colleagues demonstrated decreased intubation rates and mortality with the application of NPPV in immunosuppressed patients with hypoxemic respiratory failure, fever, and pulmonary infiltrates.¹⁶

In this study, immunosuppression occurred most commonly as a result of malignancy. In the group receiving NPPV alternating with oxygen (at least 45 minutes of NPPV alternated every three hours with periods of spontaneous breathing), the rate of subsequent intubation decreased to 46%, compared with 77% in those receiving oxygen alone. The mortality rate was 38% in the NPPV group, as compared with 69% in the standard treatment group.

Though the outcomes in immunocompromised patients with hypoxemia, fever, and pulmonary infiltrates were very poor (38% mortality even with NPPV), this small study and recent guidelines suggest a trial of NPPV in this population.^4,16

Other indications. NPPV has been applied in multiple other clinical scenarios, including exacerbation of asthma, community-acquired pneumonia, acute lung injury, and bronchoscopy in hypoxemic patients. It has also been evaluated in the postsurgical period and in chest trauma. There are mixed and less robust data in these various applications, and larger controlled trials are lacking.

In asthma exacerbation, NPPV may improve dyspnea, but data regarding outcomes (intubation, mortality) are lacking. A 2005 Cochrane review concluded that data remain controversial due to insufficient evidence, and guidelines make no recommendations concerning NPPV in asthma exacerbation.^4,17 Similarly, in community-acquired pneumonia without prior history of COPD, there is no major role for NPPV.^1,3,4 Limited data suggest that NPPV lacks efficacy in preventing post-surgical respiratory failure, though it may be useful in treating existing respiratory failure or preventing intubation in patients following lung resection or abdominal surgery.^1,4 In hypoxemic patients undergoing bronchoscopy, NPPV may improve oxygenation (lower respiratory rates and improved PaO2 to FiO2 ratios, compared with oxygen alone) as well as hemodynamics (minimizing the drop in mean arterial pressure). However, outcome data are lacking and the data set is small.^4,18 In acute lung injury/acute respiratory distress syndrome, data are also limited, but NPPV appears to have a high failure rate and confers little benefit.^1,4

Back to the Case

The patient was admitted to the hospital and placed on BiPAP for approximately 1.5 hours. The patient’s respiratory rate improved to 20/minute and he appeared increasingly comfortable and alert. A repeat ABG revealed improved hypercarbia and acidosis. He was continued on steroids and antibiotics and eventually was weaned from BiPAP and discharged home.

Bottom Line

NPPV is an effective method to decrease mortality, intubation rates, and duration of ICU stay in severe exacerbations of COPD, cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates, and hypoxia, and as a bridge to extubation in COPD patients.

Dr. Kraynek is an internal medicine resident in the Department of Medicine at the University of Washington School of Medicine in Seattle. Dr. Best is assistant professor of medicine in the Division of General Internal Medicine at the University of Washington School of Medicine.

References

1. Ambrosino N, Vagheggini G. Noninvasive positive pressure ventilation in the acute care setting: where are we? Euro Resp J. 2008;31:874-856.
2. American Thoracic Society. International Consensus Conferences in Intensive Care Medicine: Noninvasive Positive Pressure Ventilation in Acute Respiratory Failure. Am J Respir Crit Care Med. 2001;163:283-291.
3. Liesching T, Kwok H, Hill N. Acute applications of noninvasive positive pressure ventilation. Chest. 2003;124:699-713.
4. Keenan S, Sinuff T, Burns K, et al. Clinical practice guidelines for the use of noninvasive positive pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. CMAJ. 2001;183:E195-E214.
5. Lightowler J, Wedzicha J, Elliot M, Ram F. Noninvasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ. 2003;326:185.
6. Quon B, Gan W, Sin D. Contemporary management of acute exacerbations of COPD: a systematic review of the metaanalysis. Chest. 2008;133:756-766.
7. Keenan S, Sinuff T, Cook D, Hill, N. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive pressure ventilation? Ann Intern Med. 2003;138:861-870.
8. Scala R, Naldi M, Archinucci I, Conigilo G, Nava S. Noninvasive positive pressure ventilation in patients with acute exacerbations of COPD and varying levels of consciousness. Chest. 2005;128:1657-1666.
9. Masip J, Roque M, Sanchez B, Fernandez R, Subirana M, Exposito J. Noninvasive ventilation in acute cardiogenic pulmonary edema. JAMA. 2005;294:3124-3130.
10. Peter J, Moran J, Phillips-Hughes J, Graham P, Bersten A. Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-anaylsis. Lancet. 2006;367:1155-1163.
11. Weng C, Zhao Y, Liu Q, et al. Meta-analysis: noninvasive ventilation in acute cardiogenic pulmonary edema. Ann Intern Med. 2010;152:560-600.
12. Keenan S, Sinuff T, Cook D, Hill N. Does noninvasive positive pressure ventilation improve outcome in acute hypoxemic respiratory failure? A systematic review. Crit Care Med. 2004;32:2516-2523.
13. Esteban A, Frutos-Vivar F, Fergusun N, et al. Noninvasive positive pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350:2452-2460.
14. Nava S, Ambrosino N, Clinie E, et al. Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease: a randomized, controlled trial. Ann Intern Med. 1998;128:721-728.
15. Grault C, Daudenthun I, Chevron V, et al. Noninvasive ventilation as a systematic extubation and weaning technique in acute on chronic respiratory failure: a prospective, randomized controlled study. Am J Respir Crit Care Med. 1999;160:86-92.
16. Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med. 2001;344:481-487.
17. Ram FSF, Wellington SR, Rowe BH, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database of Systematic Reviews. 2005, Issue 3.
18. Antonelli M, Conti G, Rocco M, et al. Noninvasive positive pressure ventilation vs. conventional oxygen supplementation in hypoxemic patients undergoing diagnostic bronchoscopy. Chest. 2002;121:1149-1154.

click for large version

Case

A 63-year-old man with severe chronic obstructive pulmonary disease (COPD) presents with one week of increasing sputum, cough, and dyspnea. His respiratory rate is 26/minute and oxygen saturation is 86% on room air (RA). He is lethargic and appears mildly uncomfortable, but he responds appropriately to questions in three- to four-word sentences. He is tachypneic with accessory muscle use and has diffuse wheezes throughout his bilateral lung fields. His initial room air arterial blood gas (ABG) is 7.32/68/86/32. Chest radiograph is notable for flattened hemidiaphragms without focal opacity. The patient is placed on oxygen and receives prednisone with nebulized albuterol and ipratropium, but his dyspnea and tachypnea persist. Due to his respiratory distress, bilevel positive airway pressure (BiPAP) is considered.

What are the clinical indications for noninvasive positive pressure ventilation (NPPV)?

Overview

NPPV assists ventilation by delivering positive expiratory and/or inspiratory pressure without the use of an endotracheal tube. Theoretically, NPPV is a preferred method of ventilation as it may eliminate the need for endotracheal intubation and its associated morbidity and mortality, including airway trauma, loss of airway defense mechanisms (ventilator-associated pneumonia), mechanical ventilation (barotrauma), and disruption of speech and swallowing.¹

NPPV is generally delivered via full-face mask or nasal mask. Nasal mask is often preferred for patient comfort, though air leaks occur with mouth breathing. There is no difference between nasal and full-face masks in outcomes including intubation rates and mortality.^2,3,4 NPPV can be delivered via a portable or standard ventilator using the same modes available for endotracheal intubation, though pressure-cycled ventilators utilizing continuous positive airway pressure (CPAP) and BiPAP are most common. CPAP delivers air at a continuous fixed pressure throughout the respiratory cycle. BiPAP delivers positive pressure at alternating levels—higher for inspiration and lower for expiration. Guidelines suggest choosing a mode based on the etiology and pathophysiology of the respiratory failure and leveraging local comfort and expertise.^2,3

In general, good candidates for NPPV display signs of tachypnea and dyspnea due to hypoxic or hypercapnic respiratory failure but are hemodynamically stable, without excessive secretions, and can protect their airway and achieve a proper seal with the mask.³ Difficulty may arise due to patient intolerance, claustrophobia, gastric distention, and poor fit that leads to air leak or skin erosion. With initiation of NPPV, patients should be followed in a care setting with the capacity for frequent monitoring and, if needed, quick access to invasive airway management. Monitoring should include patient comfort and ability to tolerate the device, vital signs, breathing pattern, oxygen saturation, ABG, and mental status. This initial evaluation may help predict the success of NPPV (see Table 2). Appropriately chosen candidates who do well with NPPV often demonstrate respiratory turnaround in a relatively brief interval^.2,3

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Review of the Data

NPPV is increasingly utilized in a variety of clinical situations. In 2000, the American Thoracic Society published consensus guidelines on the use of NPPV in acute respiratory failure.² More recently, the Canadian Medical Association developed clinical guidelines for the use of NPPV in the acute-care setting.⁴ Clinical scenarios in which there is evidence for the efficacy of NPPV include severe exacerbations of COPD, cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates, and hypoxia; it can also be used as a bridge to extubation in COPD patients.^1-4

Acute exacerbation of COPD. Several randomized controlled trials (RCT) and meta-analyses have assessed the potential benefits of NPPV in patients with acute exacerbations of COPD. In COPD, NPPV improves gas exchange and facilitates respiratory muscle rest to decrease the work of breathing, which allows for respiratory recovery and time to effectiveness of standard therapies.⁵ Multiple trials have demonstrated that the addition of NPPV to usual care decreases intubation and mortality rates, as well as hospital lengths of stay (LOS).^5-8

A Cochrane review of eight RCTs comparing NPPV with usual care noted a greater than 50% reduction in risk of intubation, and a number needed to treat (NNT) of eight patients to prevent one death.⁵ Quon and colleagues also compared NPPV to usual care in a meta-analysis of 14 trials.⁶ Eleven of these trials evaluated hospital mortality, which was decreased by 55% in patients receiving NPPV. Twelve trials assessed need for intubation, which decreased by 65%. In these trials, BiPAP was the most commonly used modality (see Table 3, for a comparison of NPPV modalities). Study patients had an average pH of 7.31 with an average PaCO2 of 68 mmHg. It was noted that the beneficial effects of NPPV increased as pH decreased. An earlier meta-analysis from Keenan and colleagues supported this notion, noting that the subgroup of patients with pH <7.3 benefited most in terms of decreased rates of intubation, hospital LOS, and hospital mortality.7 In this 2003 study, patients with relatively mild exacerbations of COPD did not benefit from the addition of NPPV to usual care. Based on the amount of positive evidence, NPPV is recommended in patients experiencing severe exacerbations of COPD as evidenced by a pH <7.35 and relative hypercarbia.^1,2,4,7

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Cardiogenic pulmonary edema. In patients with acute cardiogenic pulmonary edema, NPPV has been found to be beneficial, decreasing mortality, rates of intubation, and hospital LOS. Physiologically, NPPV augments cardiac output, improves respiratory mechanics, and decreases afterload.10 Cardiogenic edema is variably defined and has a number of causes elucidated in an analysis of 11 RCTs conducted by Masip and colleagues. These causes included acute coronary syndrome (31%), hypertension (27%), congestive heart failure (14%), and a combination of respiratory infection, arrhythmia, volume overload, and treatment noncompliance (28%).⁹ In this analysis, CPAP and BiPAP demonstrated a combined 43% reduction in mortality and a 57% reduction in intubation. More recently, Peter and colleagues described a statistically significant reduction in hospital mortality and the need for intubation with CPAP, while BiPAP only demonstrated a statistically significant decrease in need for intubation.¹⁰ Thus, there appears to be some evidence that CPAP is the preferred NPPV mode in patients with acute cardiogenic pulmonary edema. Despite inclusion of a recent, large RCT showing no benefit of NPPV versus usual care in cardiogenic pulmonary edema, the overall positive effect of NPPV persisted, particularly when the cause of pulmonary edema was acute coronary syndrome.¹¹

Weaning after intubation. NPPV has been evaluated as a method to facilitate early extubation, as a measure to prevent extubation failure, and as a treatment modality for respiratory failure following extubation, with mixed results.^12,13 In 1998, a small trial compared the use of NPPV in COPD patients to facilitate early extubation with a standard weaning protocol. In this population, early NPPV resulted in better weaning rates with shorter times of mechanical ventilation (10 vs. 16 days), fewer days in the ICU, and improved 60-day survival rates (92% vs. 72%).^3,14 In another RCT not limited to COPD patients, Grault and colleagues found that NPPV reduced the duration of intubation (4.5 vs. 7.6 days) but was not associated with benefits in ICU length of stay or survival previously described.^3,15 Thus, though NPPV may be beneficial in facilitating early extubation in COPD patients, it is not recommended in other patient populations.⁴

NPPV has also been evaluated as a measure to prevent respiratory failure in patients at high risk for extubation failure. When applied immediately after extubation in patients with COPD and obesity, NPPV reduced reintubation rates and ICU mortality.^3,4 In 2004, Esteban and colleagues examined NPPV in patients who had respiratory failure following extubation. In this setting, NPPV was ineffective at preventing reintubation and had no survival benefit.

In summary, NPPV may facilitate early extubation and prevent extubation failure in appropriate patients, such as those with COPD, but is unlikely to be beneficial and is not recommended in patients with existing respiratory failure after extubation.^4,15

Immunosuppressed patients. A 2001 single-center, randomized-controlled trial by Holbert and colleagues demonstrated decreased intubation rates and mortality with the application of NPPV in immunosuppressed patients with hypoxemic respiratory failure, fever, and pulmonary infiltrates.¹⁶

In this study, immunosuppression occurred most commonly as a result of malignancy. In the group receiving NPPV alternating with oxygen (at least 45 minutes of NPPV alternated every three hours with periods of spontaneous breathing), the rate of subsequent intubation decreased to 46%, compared with 77% in those receiving oxygen alone. The mortality rate was 38% in the NPPV group, as compared with 69% in the standard treatment group.

Though the outcomes in immunocompromised patients with hypoxemia, fever, and pulmonary infiltrates were very poor (38% mortality even with NPPV), this small study and recent guidelines suggest a trial of NPPV in this population.^4,16

Other indications. NPPV has been applied in multiple other clinical scenarios, including exacerbation of asthma, community-acquired pneumonia, acute lung injury, and bronchoscopy in hypoxemic patients. It has also been evaluated in the postsurgical period and in chest trauma. There are mixed and less robust data in these various applications, and larger controlled trials are lacking.

In asthma exacerbation, NPPV may improve dyspnea, but data regarding outcomes (intubation, mortality) are lacking. A 2005 Cochrane review concluded that data remain controversial due to insufficient evidence, and guidelines make no recommendations concerning NPPV in asthma exacerbation.^4,17 Similarly, in community-acquired pneumonia without prior history of COPD, there is no major role for NPPV.^1,3,4 Limited data suggest that NPPV lacks efficacy in preventing post-surgical respiratory failure, though it may be useful in treating existing respiratory failure or preventing intubation in patients following lung resection or abdominal surgery.^1,4 In hypoxemic patients undergoing bronchoscopy, NPPV may improve oxygenation (lower respiratory rates and improved PaO2 to FiO2 ratios, compared with oxygen alone) as well as hemodynamics (minimizing the drop in mean arterial pressure). However, outcome data are lacking and the data set is small.^4,18 In acute lung injury/acute respiratory distress syndrome, data are also limited, but NPPV appears to have a high failure rate and confers little benefit.^1,4

Back to the Case

The patient was admitted to the hospital and placed on BiPAP for approximately 1.5 hours. The patient’s respiratory rate improved to 20/minute and he appeared increasingly comfortable and alert. A repeat ABG revealed improved hypercarbia and acidosis. He was continued on steroids and antibiotics and eventually was weaned from BiPAP and discharged home.

Bottom Line

NPPV is an effective method to decrease mortality, intubation rates, and duration of ICU stay in severe exacerbations of COPD, cardiogenic pulmonary edema, immunosuppressed patients with pulmonary infiltrates, and hypoxia, and as a bridge to extubation in COPD patients.

Dr. Kraynek is an internal medicine resident in the Department of Medicine at the University of Washington School of Medicine in Seattle. Dr. Best is assistant professor of medicine in the Division of General Internal Medicine at the University of Washington School of Medicine.

References

1. Ambrosino N, Vagheggini G. Noninvasive positive pressure ventilation in the acute care setting: where are we? Euro Resp J. 2008;31:874-856.
2. American Thoracic Society. International Consensus Conferences in Intensive Care Medicine: Noninvasive Positive Pressure Ventilation in Acute Respiratory Failure. Am J Respir Crit Care Med. 2001;163:283-291.
3. Liesching T, Kwok H, Hill N. Acute applications of noninvasive positive pressure ventilation. Chest. 2003;124:699-713.
4. Keenan S, Sinuff T, Burns K, et al. Clinical practice guidelines for the use of noninvasive positive pressure ventilation and noninvasive continuous positive airway pressure in the acute care setting. CMAJ. 2001;183:E195-E214.
5. Lightowler J, Wedzicha J, Elliot M, Ram F. Noninvasive positive pressure ventilation to treat respiratory failure resulting from exacerbations of chronic obstructive pulmonary disease: Cochrane systematic review and meta-analysis. BMJ. 2003;326:185.
6. Quon B, Gan W, Sin D. Contemporary management of acute exacerbations of COPD: a systematic review of the metaanalysis. Chest. 2008;133:756-766.
7. Keenan S, Sinuff T, Cook D, Hill, N. Which patients with acute exacerbation of chronic obstructive pulmonary disease benefit from noninvasive positive pressure ventilation? Ann Intern Med. 2003;138:861-870.
8. Scala R, Naldi M, Archinucci I, Conigilo G, Nava S. Noninvasive positive pressure ventilation in patients with acute exacerbations of COPD and varying levels of consciousness. Chest. 2005;128:1657-1666.
9. Masip J, Roque M, Sanchez B, Fernandez R, Subirana M, Exposito J. Noninvasive ventilation in acute cardiogenic pulmonary edema. JAMA. 2005;294:3124-3130.
10. Peter J, Moran J, Phillips-Hughes J, Graham P, Bersten A. Effect of non-invasive positive pressure ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-anaylsis. Lancet. 2006;367:1155-1163.
11. Weng C, Zhao Y, Liu Q, et al. Meta-analysis: noninvasive ventilation in acute cardiogenic pulmonary edema. Ann Intern Med. 2010;152:560-600.
12. Keenan S, Sinuff T, Cook D, Hill N. Does noninvasive positive pressure ventilation improve outcome in acute hypoxemic respiratory failure? A systematic review. Crit Care Med. 2004;32:2516-2523.
13. Esteban A, Frutos-Vivar F, Fergusun N, et al. Noninvasive positive pressure ventilation for respiratory failure after extubation. N Engl J Med. 2004;350:2452-2460.
14. Nava S, Ambrosino N, Clinie E, et al. Noninvasive mechanical ventilation in the weaning of patients with respiratory failure due to chronic obstructive pulmonary disease: a randomized, controlled trial. Ann Intern Med. 1998;128:721-728.
15. Grault C, Daudenthun I, Chevron V, et al. Noninvasive ventilation as a systematic extubation and weaning technique in acute on chronic respiratory failure: a prospective, randomized controlled study. Am J Respir Crit Care Med. 1999;160:86-92.
16. Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med. 2001;344:481-487.
17. Ram FSF, Wellington SR, Rowe BH, Wedzicha JA. Non-invasive positive pressure ventilation for treatment of respiratory failure due to severe acute exacerbations of asthma. Cochrane Database of Systematic Reviews. 2005, Issue 3.
18. Antonelli M, Conti G, Rocco M, et al. Noninvasive positive pressure ventilation vs. conventional oxygen supplementation in hypoxemic patients undergoing diagnostic bronchoscopy. Chest. 2002;121:1149-1154.