Society News

The CHEST Board of Regents met in mid-June for its first in-person meeting in more than a year. It served as a lovely reminder that not only are in-person meetings a more effective way to conduct the business of the College, but that the members of the board have really missed seeing each other without an intervening screen and webcam.

First on the agenda was a recap by the CHEST presidents of their recent strategic retreat. Most relevant to the organization was a recommendation that we revise the manner by which the CHEST strategic plan is set. If the last year has taught us anything, it is that planning for the future is essential, but we must also allow for flexibility when external forces change what the future holds. Accordingly, we will be replacing the former 5-year planning cycle with a more nimble annual review. From a member’s standpoint, this means that you will see more frequent revisions of those plans (Strategic Plan, American College of Chest Physicians).

Over the last year, the CHEST Foundation has sponsored a series of “listening tours,” which has allowed our members and leaders to hear from many of our patients who feel disenfranchised from the medical system because of struggles with communication, finances, and access, among other issues. The willingness of our patients to share their struggles with us has inspired the Foundation to try to make inroads into these, better navigating these barriers. In direct response to what we’ve heard, the team is designing programs to help our caregivers focus on the psychological, social, environmental, and personal factors that impact our patients’ ability to obtain the critical health care that all need and deserve.

Our ability to execute and deliver such programs is contingent on successful fundraising efforts. Ian Nathanson, president of the CHEST Foundation, reviewed fundraising progress with the board. Over these long months, donors, participants, and friends of the Foundation have participated in virtual events designed to foster engagement and comradery through this difficult time. This June, we held a virtual and in-person Belmont Stakes event that has shown that we can adapt to challenging times and that our membership is still incredibly supportive of the Foundation’s mission. Thank you to all of you who participated in or donated to the CHEST Foundation over the last year!

The last 18 months have had a marked impact on our ability to provide the live, interactive learning experiences for which CHEST is known, but efforts in the remote learning space have yielded impressive increases in both the number of remote learning opportunities and the breadth of our members who are using them. As one example, the number of CHEST podcast views quadrupled last year compared with 2019. Although CHEST reopened its headquarters for live learning opportunities this summer, and we are looking to move significantly back toward “business as usual” with CHEST 2021 in Orlando this October, we will also be carefully considering how best to incorporate the lessons learned in the remote offering space as the world reopens in the coming year.

Neil Freedman, chair of CHEST’s Health Advocacy and Policy Committee (HPAC), presented a review of the committee’s work since its inception just over 1 year ago. In addition to putting together a multi-society Technical Expert Panel on the use and coverage of noninvasive ventilation, HPAC worked with 18 other societies in drafting a response to the Agency for Healthcare Research and Quality’s draft on coverage for CPAP therapy for obstructive sleep apnea. For members interested in getting more involved in CHEST’s advocacy efforts, we are seeking self-nominations for members of several working groups (nominations to open soon); in addition, there will be sessions during CHEST 2021 focused on our advocacy efforts and how you can participate, as well as best practices in the advocacy space.

Several months ago, the Exeter Group was asked by the board to analyze how CHEST can expand our organizational efforts in diversity, equity, and inclusion (DEI). Representatives from the Exeter Group joined the meeting to provide board members with preliminary data. Limited interviews with both members and staff have begun to provide a picture of where CHEST has already made some progress in this space, and where our ongoing challenges and opportunities for improvement still exist; it is clear that there is a wide range of opinions on these complicated issues. As our consultants are only 1 month into this 6-month phase of the project, we expect a great deal more information to come, with a plan for ongoing surveys of and focus groups for our members; when you receive one of these requests, please make every effort to complete it as candidly as possible, regardless of your viewpoint. The consulting work will culminate with a final presentation to the board just before the annual meeting in the fall, with specific recommendations on organizational actions that will be used to implement a multiyear DEI plan.

The Governance Committee, represented by Stephanie Levine, made several recommendations to revision of the CHEST Foundations bylaws. Specifically, the new bylaws permit Trustees of the Foundation to be re-elected to positions on the board beyond the current 6-year maximum term after several years away from the position. The position of President-Designate of the Foundation will also be eliminated, allowing for a 2-year term for the President-Elect of the Foundation and a 2-year term for the President of the Foundation.

One of the main challenges for an organization of 19,000 people is to ensure that we can engage as many of our members as possible. The NetWorks structure has historically been the primary mechanism for members to pursue initial leadership opportunities within the College. CHEST Past-President Stephanie Levine previously established a working group to revisit NetWork structure in an effort to ensure ample opportunities for engagement within CHEST. The final agenda item at this board meeting was a discussion about restructuring the CHEST NetWorks to create mechanisms that will help us balance the needs of the College with the energy of the volunteers to maximize productivity and engagement of all parties. The plan would increase the number of leadership positions available within the NetWork structure. While the final nomenclature and distribution of NetWorks amongst the pillars has yet to be finalized, the board was supportive of this modification and expects implementation in the next 12 months, with details to be provided to the membership as they are fleshed out.

After a full day’s agenda, CHEST President Steve Simpson adjourned the board meeting. The Board of Regents will meet remotely in August (the summer call has always been a remote meeting) and again in Orlando in October.

The CHEST Board of Regents met in mid-June for its first in-person meeting in more than a year. It served as a lovely reminder that not only are in-person meetings a more effective way to conduct the business of the College, but that the members of the board have really missed seeing each other without an intervening screen and webcam.

First on the agenda was a recap by the CHEST presidents of their recent strategic retreat. Most relevant to the organization was a recommendation that we revise the manner by which the CHEST strategic plan is set. If the last year has taught us anything, it is that planning for the future is essential, but we must also allow for flexibility when external forces change what the future holds. Accordingly, we will be replacing the former 5-year planning cycle with a more nimble annual review. From a member’s standpoint, this means that you will see more frequent revisions of those plans (Strategic Plan, American College of Chest Physicians).

Over the last year, the CHEST Foundation has sponsored a series of “listening tours,” which has allowed our members and leaders to hear from many of our patients who feel disenfranchised from the medical system because of struggles with communication, finances, and access, among other issues. The willingness of our patients to share their struggles with us has inspired the Foundation to try to make inroads into these, better navigating these barriers. In direct response to what we’ve heard, the team is designing programs to help our caregivers focus on the psychological, social, environmental, and personal factors that impact our patients’ ability to obtain the critical health care that all need and deserve.

Our ability to execute and deliver such programs is contingent on successful fundraising efforts. Ian Nathanson, president of the CHEST Foundation, reviewed fundraising progress with the board. Over these long months, donors, participants, and friends of the Foundation have participated in virtual events designed to foster engagement and comradery through this difficult time. This June, we held a virtual and in-person Belmont Stakes event that has shown that we can adapt to challenging times and that our membership is still incredibly supportive of the Foundation’s mission. Thank you to all of you who participated in or donated to the CHEST Foundation over the last year!

The last 18 months have had a marked impact on our ability to provide the live, interactive learning experiences for which CHEST is known, but efforts in the remote learning space have yielded impressive increases in both the number of remote learning opportunities and the breadth of our members who are using them. As one example, the number of CHEST podcast views quadrupled last year compared with 2019. Although CHEST reopened its headquarters for live learning opportunities this summer, and we are looking to move significantly back toward “business as usual” with CHEST 2021 in Orlando this October, we will also be carefully considering how best to incorporate the lessons learned in the remote offering space as the world reopens in the coming year.

Neil Freedman, chair of CHEST’s Health Advocacy and Policy Committee (HPAC), presented a review of the committee’s work since its inception just over 1 year ago. In addition to putting together a multi-society Technical Expert Panel on the use and coverage of noninvasive ventilation, HPAC worked with 18 other societies in drafting a response to the Agency for Healthcare Research and Quality’s draft on coverage for CPAP therapy for obstructive sleep apnea. For members interested in getting more involved in CHEST’s advocacy efforts, we are seeking self-nominations for members of several working groups (nominations to open soon); in addition, there will be sessions during CHEST 2021 focused on our advocacy efforts and how you can participate, as well as best practices in the advocacy space.

Several months ago, the Exeter Group was asked by the board to analyze how CHEST can expand our organizational efforts in diversity, equity, and inclusion (DEI). Representatives from the Exeter Group joined the meeting to provide board members with preliminary data. Limited interviews with both members and staff have begun to provide a picture of where CHEST has already made some progress in this space, and where our ongoing challenges and opportunities for improvement still exist; it is clear that there is a wide range of opinions on these complicated issues. As our consultants are only 1 month into this 6-month phase of the project, we expect a great deal more information to come, with a plan for ongoing surveys of and focus groups for our members; when you receive one of these requests, please make every effort to complete it as candidly as possible, regardless of your viewpoint. The consulting work will culminate with a final presentation to the board just before the annual meeting in the fall, with specific recommendations on organizational actions that will be used to implement a multiyear DEI plan.

The Governance Committee, represented by Stephanie Levine, made several recommendations to revision of the CHEST Foundations bylaws. Specifically, the new bylaws permit Trustees of the Foundation to be re-elected to positions on the board beyond the current 6-year maximum term after several years away from the position. The position of President-Designate of the Foundation will also be eliminated, allowing for a 2-year term for the President-Elect of the Foundation and a 2-year term for the President of the Foundation.

One of the main challenges for an organization of 19,000 people is to ensure that we can engage as many of our members as possible. The NetWorks structure has historically been the primary mechanism for members to pursue initial leadership opportunities within the College. CHEST Past-President Stephanie Levine previously established a working group to revisit NetWork structure in an effort to ensure ample opportunities for engagement within CHEST. The final agenda item at this board meeting was a discussion about restructuring the CHEST NetWorks to create mechanisms that will help us balance the needs of the College with the energy of the volunteers to maximize productivity and engagement of all parties. The plan would increase the number of leadership positions available within the NetWork structure. While the final nomenclature and distribution of NetWorks amongst the pillars has yet to be finalized, the board was supportive of this modification and expects implementation in the next 12 months, with details to be provided to the membership as they are fleshed out.

After a full day’s agenda, CHEST President Steve Simpson adjourned the board meeting. The Board of Regents will meet remotely in August (the summer call has always been a remote meeting) and again in Orlando in October.

The CHEST Board of Regents met in mid-June for its first in-person meeting in more than a year. It served as a lovely reminder that not only are in-person meetings a more effective way to conduct the business of the College, but that the members of the board have really missed seeing each other without an intervening screen and webcam.

First on the agenda was a recap by the CHEST presidents of their recent strategic retreat. Most relevant to the organization was a recommendation that we revise the manner by which the CHEST strategic plan is set. If the last year has taught us anything, it is that planning for the future is essential, but we must also allow for flexibility when external forces change what the future holds. Accordingly, we will be replacing the former 5-year planning cycle with a more nimble annual review. From a member’s standpoint, this means that you will see more frequent revisions of those plans (Strategic Plan, American College of Chest Physicians).

Over the last year, the CHEST Foundation has sponsored a series of “listening tours,” which has allowed our members and leaders to hear from many of our patients who feel disenfranchised from the medical system because of struggles with communication, finances, and access, among other issues. The willingness of our patients to share their struggles with us has inspired the Foundation to try to make inroads into these, better navigating these barriers. In direct response to what we’ve heard, the team is designing programs to help our caregivers focus on the psychological, social, environmental, and personal factors that impact our patients’ ability to obtain the critical health care that all need and deserve.

Our ability to execute and deliver such programs is contingent on successful fundraising efforts. Ian Nathanson, president of the CHEST Foundation, reviewed fundraising progress with the board. Over these long months, donors, participants, and friends of the Foundation have participated in virtual events designed to foster engagement and comradery through this difficult time. This June, we held a virtual and in-person Belmont Stakes event that has shown that we can adapt to challenging times and that our membership is still incredibly supportive of the Foundation’s mission. Thank you to all of you who participated in or donated to the CHEST Foundation over the last year!

The last 18 months have had a marked impact on our ability to provide the live, interactive learning experiences for which CHEST is known, but efforts in the remote learning space have yielded impressive increases in both the number of remote learning opportunities and the breadth of our members who are using them. As one example, the number of CHEST podcast views quadrupled last year compared with 2019. Although CHEST reopened its headquarters for live learning opportunities this summer, and we are looking to move significantly back toward “business as usual” with CHEST 2021 in Orlando this October, we will also be carefully considering how best to incorporate the lessons learned in the remote offering space as the world reopens in the coming year.

Neil Freedman, chair of CHEST’s Health Advocacy and Policy Committee (HPAC), presented a review of the committee’s work since its inception just over 1 year ago. In addition to putting together a multi-society Technical Expert Panel on the use and coverage of noninvasive ventilation, HPAC worked with 18 other societies in drafting a response to the Agency for Healthcare Research and Quality’s draft on coverage for CPAP therapy for obstructive sleep apnea. For members interested in getting more involved in CHEST’s advocacy efforts, we are seeking self-nominations for members of several working groups (nominations to open soon); in addition, there will be sessions during CHEST 2021 focused on our advocacy efforts and how you can participate, as well as best practices in the advocacy space.

Several months ago, the Exeter Group was asked by the board to analyze how CHEST can expand our organizational efforts in diversity, equity, and inclusion (DEI). Representatives from the Exeter Group joined the meeting to provide board members with preliminary data. Limited interviews with both members and staff have begun to provide a picture of where CHEST has already made some progress in this space, and where our ongoing challenges and opportunities for improvement still exist; it is clear that there is a wide range of opinions on these complicated issues. As our consultants are only 1 month into this 6-month phase of the project, we expect a great deal more information to come, with a plan for ongoing surveys of and focus groups for our members; when you receive one of these requests, please make every effort to complete it as candidly as possible, regardless of your viewpoint. The consulting work will culminate with a final presentation to the board just before the annual meeting in the fall, with specific recommendations on organizational actions that will be used to implement a multiyear DEI plan.

The Governance Committee, represented by Stephanie Levine, made several recommendations to revision of the CHEST Foundations bylaws. Specifically, the new bylaws permit Trustees of the Foundation to be re-elected to positions on the board beyond the current 6-year maximum term after several years away from the position. The position of President-Designate of the Foundation will also be eliminated, allowing for a 2-year term for the President-Elect of the Foundation and a 2-year term for the President of the Foundation.

One of the main challenges for an organization of 19,000 people is to ensure that we can engage as many of our members as possible. The NetWorks structure has historically been the primary mechanism for members to pursue initial leadership opportunities within the College. CHEST Past-President Stephanie Levine previously established a working group to revisit NetWork structure in an effort to ensure ample opportunities for engagement within CHEST. The final agenda item at this board meeting was a discussion about restructuring the CHEST NetWorks to create mechanisms that will help us balance the needs of the College with the energy of the volunteers to maximize productivity and engagement of all parties. The plan would increase the number of leadership positions available within the NetWork structure. While the final nomenclature and distribution of NetWorks amongst the pillars has yet to be finalized, the board was supportive of this modification and expects implementation in the next 12 months, with details to be provided to the membership as they are fleshed out.

After a full day’s agenda, CHEST President Steve Simpson adjourned the board meeting. The Board of Regents will meet remotely in August (the summer call has always been a remote meeting) and again in Orlando in October.

Airways disorders

Eosinophils in COPD

Using peripheral blood eosinophilia (PBE) as a treatable biomarker of airway inflammation in patients with COPD has become an area of controversy in pulmonary medicine.

The proponents find a role for PBE testing in initiation and withdrawal of inhaled corticosteroids (ICS) and as a target for monoclonal antibodies in future studies.¹ Post hoc analyses showed that variable doses of ICS/LABA combination compared with LABA alone in COPD patients were associated with much higher exacerbation reduction in patients with eosinophils counts of ≥2% and magnitude of effect proportionally increased from 29% to 42% with increasing eosinophil count from ≥2% to ≥6% suggesting a dose-response relationship.² A post hoc analysis of the WISDOM trial showed increased risk of exacerbation after ICS discontinuation in COPD patients with high eosinophils (≥300 cells/mcL or ≥4%) while exacerbation risk was not increased in patients with low eosinophils (<150 cells/mcL or <2%).³

The opponents of eosinophil-guided therapy object that the level of evidence is weak as this is based on the post hoc analyses of randomized control trials on patients with increased exacerbation risk at baseline, which in itself is an independent predictor of future exacerbations.⁴ Some observational studies failed to find increased risk of exacerbation with higher eosinophil count while others found that higher eosinophil count was associated with increased survival and better quality of life.^5,6 Anti-eosinophilic biologics have failed to show consistent benefit in exacerbation reduction in COPD patients so far, despite showing a reduction in the PBE.^7-9

The GOLD COPD Guidelines support the use of ICS in patients with eosinophils >300 cells/mcL especially with a history of exacerbation and recommend against ICS in patients with eosinophils <100 cells/mcL.¹⁰

Farrukh Abbas, MD
Steering Committee Fellow-in-Training
Allen J. Blaivas, MD, FCCP
NetWork Chair
 

References

1. Wade RC and Wells JM. Chest. 2020;157(5):1073-5.

2. Pascoe S et al. The Lancet Respir Med. 2015;3(6):435-42.

3. Watz H et al. The Lancet Respir Med. 2016;4(5):390-8.

4. Criner GJ. Chest. 2020;157(5):1075-8.

5. Shin SH et al. Respir Res. 2018;19(1):134.

6. Casanova C et al. Eur Respir J. 2017;50(5):1701162.

7. Pavord ID et al. N Engl J Med. 2017;377(17):1613-29.

8. Criner GJ et al. N Engl J Med. 2019;381(11):1023-34.

9. Mycroft K et al. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2565-74.

10. Global Initiative for Chronic Obstructive Lung Disease 2021 Report.
 

Clinical research

Long-COVID: COVID-19 disease beyond the pandemic

There are increasing reports of persistent multiorgan symptoms following COVID-19 infection.

In December 2020, the National Institute for Health and Care Excellence (NICE) developed guidelines, based primarily on expert opinion, to define and manage ongoing symptomatic COVID-19 (symptoms for 4-12 weeks after infection) and post-COVID syndrome (symptoms present for > 12 weeks without alternative explanation). Subsequently, the National Institutes of Health (NIH), released in February 2021 an initiative to study Post-Acute Sequelae of SARS-CoV2 infection (PASC). Symptoms can include, respiratory (cough, shortness of breath), cardiac (palpitations, chest pain), fatigue and physical limitations, and neurologic (depression, insomnia, cognitive impairment) (Lancet 2020 Dec 12;396[10266]:1861). The majority of patients with post-COVID syndrome have microbiological recovery (PCR negative), and often have radiological recovery. Risk factors include older age, female sex, and comorbidities (Raveendran AV. Diabetes Metab Syndr. 2021 May-June;15[3]:869-75).

Diagnosis and access to care pose significant challenges for post-COVID syndrome, and it is difficult to estimate exactly how many are affected – one report from Italy found that up to 87% of discharged hospitalized patients had persistent symptom(s) at 60 days (Carfi A. JAMA 2020 Aug;324[6]:603-5). Thus far, management recommendations include a multidisciplinary approach to evaluation, symptomatic treatment, organ specific treatment (for example, consideration of corticosteroids for persistent inflammatory interstitial lung disease) (Myall KJ. Ann Am Thorac Soc. 2021 May;8[5]:799-806), physical/occupational therapy, and psychological support. Many institutions have established, or are working to establish post-COVID clinics (Aging Clin Exp Res. 2020 Aug;32[8]:1613-20). Currently, the NIH is offering funding opportunities and there are many clinical trials across the world actively recruiting patients.

Ankita Agarwal, MD
Steering Committee Fellow-in-Training
Bharat Bajantri, MD
Steering Committee Member
Aravind Menon, MD
Steering Committee Fellow-in-Training
 

Critical care

Sedation practices in the ICU: Moving past the COVID-19 pandemic

The COVID-19 pandemic brought unprecedented change to critical care practice patterns, and sedation practices in the intensive care unit are no exception. In a large cohort analysis of over 2,000 adults with COVID-19 (Pun BT, et al. Lancet Respir Med. 2021;9[3]:239-50), 64% of patients received benzodiazepines (median of 7 days), and patients were deeply sedated. More than half of the patients were delirious, with benzodiazepine use associated with increased incidence of delirium. These observations represent a significant departure from well-established pre-COVID best-practices in sedation: light targets, daily sedation interruption, and avoiding continuous benzodiazepine infusions whenever possible (Girard TD, et al. Lancet; 2008;371[9607]:126-34; Fraser GL, et al. Crit Care Med;2013 Sep;41[9 Suppl 1]:S30-8; Riker RR, et al. JAMA;2009;301[5]:489-99).

As COVID-19 case counts begin to improve in many of our communities, we have the opportunity to refocus on best sedation practices and build on a growing body of recent evidence. The MENDS2 trial, completed pre-COVID-19, assigned mechanically ventilated patients with sepsis to either propofol or dexmedetomidine and showed no difference in delirium or coma in this cohort of lightly sedated patients (Hughes CG, et al. N Engl J Med. 2021;384[15]:1424-36). Furthering this point, Olsen et al. found no difference in outcomes when mechanically ventilated patients were randomized to no sedation vs light sedation (Olsen HT, et al. N Engl J Med; 2020;382[12]:1103-11).

While the evidence surrounding sedation strategies in the critically ill continues to grow, one thing is certain: promoting lighter sedation targets and reengaging in sedation-related best practices following the COVID-19 pandemic will continue to play a vital role in improving both short and long-term outcomes for our critically ill patients.

Casey Cable, MD, MSc
Steering Committee Member

Kyle Stinehart, MD
Steering Committee Member
 

Home mechanical ventilation

How to initiate a chronic respiratory failure clinic

Noninvasive ventilation (NIV) is an established treatment for chronic hypercapnic respiratory failure from neuromuscular disorders, COPD, obesity hypoventilation syndrome (OHS), and restrictive thoracic disorders. Previously, hospital admission was considered essential for setup of chronic NIV but with advances in the modes of ventilation and remote monitoring, hospital admission has become less justifiable, especially in countries with centralized medical systems and presence of centers of excellence for home ventilation (Van Den Biggelaar RJM, et al. Chest. 2020;158[6]:2493-2501); Duiverman ML, et al. Thorax. 2020;75:244-52). In the United States, where centralized health care is atypical, management of NIV has been disparate with no clear consensus on practice patterns. Thus, we hope to provide some guidance toward the establishment of such clinics in the U.S.
 

Prior to developing an NIV clinic, establishing a referral source from neuromuscular, rehabilitation/spinal cord injury, bariatric surgery, and COPD programs is important. After this, collaboration with a respiratory therapist through durable medical equipment is essential to building a robust care team. These companies are also important for assisting in remote monitoring, providing overnight pulse oximetry/CO₂ monitoring, mask fitting, and airway clearance. Clinicians are encouraged to develop protocols for initiation and titration of NIV and mouthpiece ventilation. Clinics should provide spirometry, maximal inspiratory pressure, transcutaneous CO₂, and/or blood gas testing. Additionally, in this patient population, wheelchair scales are necessary. Clinical workflow should include a review of NIV downloads, identify asynchronies and troubleshoot it in timely and reliable manner (Blouet S, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:2577-86). Lastly, effort should be made for an adequate assessment of the home situation including layout of home along with family support utilizing social worker and palliative care team. Due to patient mobility, we encourage continued availability of telehealth for these patients.

In summary, strong clinical infrastructure, a robust care team, and an efficient, secure, reliable telemonitoring system are key to provide better care to this vulnerable patient population.

Ashima S. Sahni, MD, MBBS, FCCP
NetWork Member

Amen Sergew, MD
Steering Committee Member

Interstitial and diffuse lung disease

Treatment for pulmonary hypertension secondary to interstitial lung disease

The development of pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) (PH-ILD) is associated with increased supplemental oxygen requirements, reduced functional status, and decreased survival (King CS, et al. Chest. 2020;158[4]:1651).

An inhaled formulation of treprostinil (Tyvaso) is the first treatment option approved by the FDA for patients with PH-ILD, including those with idiopathic pulmonary fibrosis, connective tissue disease-associated ILD, and combined pulmonary fibrosis and emphysema. Approval was based on results from the INCREASE trial (Waxman A, et al. N Engl J Med. 2021;384[4]:325), a phase III multicenter, randomized, double-blinded study comparing the inhaled formulation to placebo in 326 patients over a 16-week period. Participants in the treatment arm were given up to 12 breaths of the formulation per session, four times per day. Subjects treated with this inhaled formulation met the primary study endpoint, an increase in 6-minute walk distance (6MWD) from baseline to week 16, walking 21 m farther than placebo-treated control subjects. Furthermore, patients receiving the new formulation had a decrease in NT-proBNP levels (compared with increases in the placebo arm) and a reduction in clinical worsening (23% of inhalation formulation-treated vs. 33% of placebo-treated subjects). This formulation of treprostinil was well-tolerated with a safety profile consistent with common prostacyclin-related adverse events, including cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. Its approval will dramatically alter the ILD treatment landscape. It now necessitates the use of PH screening in this patient population. However, care will need to be exercised in appropriate patient selection for treatment, using the study inclusion and exclusion criteria as a starting point. Appropriate use of this formulation will hopefully help mitigate the negative outcomes impacting patients with PH-ILD.

Rebecca Anna Gersten, MD
Adrian Shifren, MD
Steering Committee Members

Airways disorders

Eosinophils in COPD

Using peripheral blood eosinophilia (PBE) as a treatable biomarker of airway inflammation in patients with COPD has become an area of controversy in pulmonary medicine.

The proponents find a role for PBE testing in initiation and withdrawal of inhaled corticosteroids (ICS) and as a target for monoclonal antibodies in future studies.¹ Post hoc analyses showed that variable doses of ICS/LABA combination compared with LABA alone in COPD patients were associated with much higher exacerbation reduction in patients with eosinophils counts of ≥2% and magnitude of effect proportionally increased from 29% to 42% with increasing eosinophil count from ≥2% to ≥6% suggesting a dose-response relationship.² A post hoc analysis of the WISDOM trial showed increased risk of exacerbation after ICS discontinuation in COPD patients with high eosinophils (≥300 cells/mcL or ≥4%) while exacerbation risk was not increased in patients with low eosinophils (<150 cells/mcL or <2%).³

The opponents of eosinophil-guided therapy object that the level of evidence is weak as this is based on the post hoc analyses of randomized control trials on patients with increased exacerbation risk at baseline, which in itself is an independent predictor of future exacerbations.⁴ Some observational studies failed to find increased risk of exacerbation with higher eosinophil count while others found that higher eosinophil count was associated with increased survival and better quality of life.^5,6 Anti-eosinophilic biologics have failed to show consistent benefit in exacerbation reduction in COPD patients so far, despite showing a reduction in the PBE.^7-9

The GOLD COPD Guidelines support the use of ICS in patients with eosinophils >300 cells/mcL especially with a history of exacerbation and recommend against ICS in patients with eosinophils <100 cells/mcL.¹⁰

Farrukh Abbas, MD
Steering Committee Fellow-in-Training
Allen J. Blaivas, MD, FCCP
NetWork Chair
 

References

1. Wade RC and Wells JM. Chest. 2020;157(5):1073-5.

2. Pascoe S et al. The Lancet Respir Med. 2015;3(6):435-42.

3. Watz H et al. The Lancet Respir Med. 2016;4(5):390-8.

4. Criner GJ. Chest. 2020;157(5):1075-8.

5. Shin SH et al. Respir Res. 2018;19(1):134.

6. Casanova C et al. Eur Respir J. 2017;50(5):1701162.

7. Pavord ID et al. N Engl J Med. 2017;377(17):1613-29.

8. Criner GJ et al. N Engl J Med. 2019;381(11):1023-34.

9. Mycroft K et al. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2565-74.

10. Global Initiative for Chronic Obstructive Lung Disease 2021 Report.
 

Clinical research

Long-COVID: COVID-19 disease beyond the pandemic

There are increasing reports of persistent multiorgan symptoms following COVID-19 infection.

In December 2020, the National Institute for Health and Care Excellence (NICE) developed guidelines, based primarily on expert opinion, to define and manage ongoing symptomatic COVID-19 (symptoms for 4-12 weeks after infection) and post-COVID syndrome (symptoms present for > 12 weeks without alternative explanation). Subsequently, the National Institutes of Health (NIH), released in February 2021 an initiative to study Post-Acute Sequelae of SARS-CoV2 infection (PASC). Symptoms can include, respiratory (cough, shortness of breath), cardiac (palpitations, chest pain), fatigue and physical limitations, and neurologic (depression, insomnia, cognitive impairment) (Lancet 2020 Dec 12;396[10266]:1861). The majority of patients with post-COVID syndrome have microbiological recovery (PCR negative), and often have radiological recovery. Risk factors include older age, female sex, and comorbidities (Raveendran AV. Diabetes Metab Syndr. 2021 May-June;15[3]:869-75).

Diagnosis and access to care pose significant challenges for post-COVID syndrome, and it is difficult to estimate exactly how many are affected – one report from Italy found that up to 87% of discharged hospitalized patients had persistent symptom(s) at 60 days (Carfi A. JAMA 2020 Aug;324[6]:603-5). Thus far, management recommendations include a multidisciplinary approach to evaluation, symptomatic treatment, organ specific treatment (for example, consideration of corticosteroids for persistent inflammatory interstitial lung disease) (Myall KJ. Ann Am Thorac Soc. 2021 May;8[5]:799-806), physical/occupational therapy, and psychological support. Many institutions have established, or are working to establish post-COVID clinics (Aging Clin Exp Res. 2020 Aug;32[8]:1613-20). Currently, the NIH is offering funding opportunities and there are many clinical trials across the world actively recruiting patients.

Ankita Agarwal, MD
Steering Committee Fellow-in-Training
Bharat Bajantri, MD
Steering Committee Member
Aravind Menon, MD
Steering Committee Fellow-in-Training
 

Critical care

Sedation practices in the ICU: Moving past the COVID-19 pandemic

The COVID-19 pandemic brought unprecedented change to critical care practice patterns, and sedation practices in the intensive care unit are no exception. In a large cohort analysis of over 2,000 adults with COVID-19 (Pun BT, et al. Lancet Respir Med. 2021;9[3]:239-50), 64% of patients received benzodiazepines (median of 7 days), and patients were deeply sedated. More than half of the patients were delirious, with benzodiazepine use associated with increased incidence of delirium. These observations represent a significant departure from well-established pre-COVID best-practices in sedation: light targets, daily sedation interruption, and avoiding continuous benzodiazepine infusions whenever possible (Girard TD, et al. Lancet; 2008;371[9607]:126-34; Fraser GL, et al. Crit Care Med;2013 Sep;41[9 Suppl 1]:S30-8; Riker RR, et al. JAMA;2009;301[5]:489-99).

As COVID-19 case counts begin to improve in many of our communities, we have the opportunity to refocus on best sedation practices and build on a growing body of recent evidence. The MENDS2 trial, completed pre-COVID-19, assigned mechanically ventilated patients with sepsis to either propofol or dexmedetomidine and showed no difference in delirium or coma in this cohort of lightly sedated patients (Hughes CG, et al. N Engl J Med. 2021;384[15]:1424-36). Furthering this point, Olsen et al. found no difference in outcomes when mechanically ventilated patients were randomized to no sedation vs light sedation (Olsen HT, et al. N Engl J Med; 2020;382[12]:1103-11).

While the evidence surrounding sedation strategies in the critically ill continues to grow, one thing is certain: promoting lighter sedation targets and reengaging in sedation-related best practices following the COVID-19 pandemic will continue to play a vital role in improving both short and long-term outcomes for our critically ill patients.

Casey Cable, MD, MSc
Steering Committee Member

Kyle Stinehart, MD
Steering Committee Member
 

Home mechanical ventilation

How to initiate a chronic respiratory failure clinic

Noninvasive ventilation (NIV) is an established treatment for chronic hypercapnic respiratory failure from neuromuscular disorders, COPD, obesity hypoventilation syndrome (OHS), and restrictive thoracic disorders. Previously, hospital admission was considered essential for setup of chronic NIV but with advances in the modes of ventilation and remote monitoring, hospital admission has become less justifiable, especially in countries with centralized medical systems and presence of centers of excellence for home ventilation (Van Den Biggelaar RJM, et al. Chest. 2020;158[6]:2493-2501); Duiverman ML, et al. Thorax. 2020;75:244-52). In the United States, where centralized health care is atypical, management of NIV has been disparate with no clear consensus on practice patterns. Thus, we hope to provide some guidance toward the establishment of such clinics in the U.S.
 

Prior to developing an NIV clinic, establishing a referral source from neuromuscular, rehabilitation/spinal cord injury, bariatric surgery, and COPD programs is important. After this, collaboration with a respiratory therapist through durable medical equipment is essential to building a robust care team. These companies are also important for assisting in remote monitoring, providing overnight pulse oximetry/CO₂ monitoring, mask fitting, and airway clearance. Clinicians are encouraged to develop protocols for initiation and titration of NIV and mouthpiece ventilation. Clinics should provide spirometry, maximal inspiratory pressure, transcutaneous CO₂, and/or blood gas testing. Additionally, in this patient population, wheelchair scales are necessary. Clinical workflow should include a review of NIV downloads, identify asynchronies and troubleshoot it in timely and reliable manner (Blouet S, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:2577-86). Lastly, effort should be made for an adequate assessment of the home situation including layout of home along with family support utilizing social worker and palliative care team. Due to patient mobility, we encourage continued availability of telehealth for these patients.

In summary, strong clinical infrastructure, a robust care team, and an efficient, secure, reliable telemonitoring system are key to provide better care to this vulnerable patient population.

Ashima S. Sahni, MD, MBBS, FCCP
NetWork Member

Amen Sergew, MD
Steering Committee Member

Interstitial and diffuse lung disease

Treatment for pulmonary hypertension secondary to interstitial lung disease

The development of pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) (PH-ILD) is associated with increased supplemental oxygen requirements, reduced functional status, and decreased survival (King CS, et al. Chest. 2020;158[4]:1651).

An inhaled formulation of treprostinil (Tyvaso) is the first treatment option approved by the FDA for patients with PH-ILD, including those with idiopathic pulmonary fibrosis, connective tissue disease-associated ILD, and combined pulmonary fibrosis and emphysema. Approval was based on results from the INCREASE trial (Waxman A, et al. N Engl J Med. 2021;384[4]:325), a phase III multicenter, randomized, double-blinded study comparing the inhaled formulation to placebo in 326 patients over a 16-week period. Participants in the treatment arm were given up to 12 breaths of the formulation per session, four times per day. Subjects treated with this inhaled formulation met the primary study endpoint, an increase in 6-minute walk distance (6MWD) from baseline to week 16, walking 21 m farther than placebo-treated control subjects. Furthermore, patients receiving the new formulation had a decrease in NT-proBNP levels (compared with increases in the placebo arm) and a reduction in clinical worsening (23% of inhalation formulation-treated vs. 33% of placebo-treated subjects). This formulation of treprostinil was well-tolerated with a safety profile consistent with common prostacyclin-related adverse events, including cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. Its approval will dramatically alter the ILD treatment landscape. It now necessitates the use of PH screening in this patient population. However, care will need to be exercised in appropriate patient selection for treatment, using the study inclusion and exclusion criteria as a starting point. Appropriate use of this formulation will hopefully help mitigate the negative outcomes impacting patients with PH-ILD.

Rebecca Anna Gersten, MD
Adrian Shifren, MD
Steering Committee Members

Airways disorders

Eosinophils in COPD

Using peripheral blood eosinophilia (PBE) as a treatable biomarker of airway inflammation in patients with COPD has become an area of controversy in pulmonary medicine.

The proponents find a role for PBE testing in initiation and withdrawal of inhaled corticosteroids (ICS) and as a target for monoclonal antibodies in future studies.¹ Post hoc analyses showed that variable doses of ICS/LABA combination compared with LABA alone in COPD patients were associated with much higher exacerbation reduction in patients with eosinophils counts of ≥2% and magnitude of effect proportionally increased from 29% to 42% with increasing eosinophil count from ≥2% to ≥6% suggesting a dose-response relationship.² A post hoc analysis of the WISDOM trial showed increased risk of exacerbation after ICS discontinuation in COPD patients with high eosinophils (≥300 cells/mcL or ≥4%) while exacerbation risk was not increased in patients with low eosinophils (<150 cells/mcL or <2%).³

The opponents of eosinophil-guided therapy object that the level of evidence is weak as this is based on the post hoc analyses of randomized control trials on patients with increased exacerbation risk at baseline, which in itself is an independent predictor of future exacerbations.⁴ Some observational studies failed to find increased risk of exacerbation with higher eosinophil count while others found that higher eosinophil count was associated with increased survival and better quality of life.^5,6 Anti-eosinophilic biologics have failed to show consistent benefit in exacerbation reduction in COPD patients so far, despite showing a reduction in the PBE.^7-9

The GOLD COPD Guidelines support the use of ICS in patients with eosinophils >300 cells/mcL especially with a history of exacerbation and recommend against ICS in patients with eosinophils <100 cells/mcL.¹⁰

Farrukh Abbas, MD
Steering Committee Fellow-in-Training
Allen J. Blaivas, MD, FCCP
NetWork Chair
 

References

1. Wade RC and Wells JM. Chest. 2020;157(5):1073-5.

2. Pascoe S et al. The Lancet Respir Med. 2015;3(6):435-42.

3. Watz H et al. The Lancet Respir Med. 2016;4(5):390-8.

4. Criner GJ. Chest. 2020;157(5):1075-8.

5. Shin SH et al. Respir Res. 2018;19(1):134.

6. Casanova C et al. Eur Respir J. 2017;50(5):1701162.

7. Pavord ID et al. N Engl J Med. 2017;377(17):1613-29.

8. Criner GJ et al. N Engl J Med. 2019;381(11):1023-34.

9. Mycroft K et al. J Allergy Clin Immunol Pract. 2020 Sep;8(8):2565-74.

10. Global Initiative for Chronic Obstructive Lung Disease 2021 Report.
 

Clinical research

Long-COVID: COVID-19 disease beyond the pandemic

There are increasing reports of persistent multiorgan symptoms following COVID-19 infection.

In December 2020, the National Institute for Health and Care Excellence (NICE) developed guidelines, based primarily on expert opinion, to define and manage ongoing symptomatic COVID-19 (symptoms for 4-12 weeks after infection) and post-COVID syndrome (symptoms present for > 12 weeks without alternative explanation). Subsequently, the National Institutes of Health (NIH), released in February 2021 an initiative to study Post-Acute Sequelae of SARS-CoV2 infection (PASC). Symptoms can include, respiratory (cough, shortness of breath), cardiac (palpitations, chest pain), fatigue and physical limitations, and neurologic (depression, insomnia, cognitive impairment) (Lancet 2020 Dec 12;396[10266]:1861). The majority of patients with post-COVID syndrome have microbiological recovery (PCR negative), and often have radiological recovery. Risk factors include older age, female sex, and comorbidities (Raveendran AV. Diabetes Metab Syndr. 2021 May-June;15[3]:869-75).

Diagnosis and access to care pose significant challenges for post-COVID syndrome, and it is difficult to estimate exactly how many are affected – one report from Italy found that up to 87% of discharged hospitalized patients had persistent symptom(s) at 60 days (Carfi A. JAMA 2020 Aug;324[6]:603-5). Thus far, management recommendations include a multidisciplinary approach to evaluation, symptomatic treatment, organ specific treatment (for example, consideration of corticosteroids for persistent inflammatory interstitial lung disease) (Myall KJ. Ann Am Thorac Soc. 2021 May;8[5]:799-806), physical/occupational therapy, and psychological support. Many institutions have established, or are working to establish post-COVID clinics (Aging Clin Exp Res. 2020 Aug;32[8]:1613-20). Currently, the NIH is offering funding opportunities and there are many clinical trials across the world actively recruiting patients.

Ankita Agarwal, MD
Steering Committee Fellow-in-Training
Bharat Bajantri, MD
Steering Committee Member
Aravind Menon, MD
Steering Committee Fellow-in-Training
 

Critical care

Sedation practices in the ICU: Moving past the COVID-19 pandemic

The COVID-19 pandemic brought unprecedented change to critical care practice patterns, and sedation practices in the intensive care unit are no exception. In a large cohort analysis of over 2,000 adults with COVID-19 (Pun BT, et al. Lancet Respir Med. 2021;9[3]:239-50), 64% of patients received benzodiazepines (median of 7 days), and patients were deeply sedated. More than half of the patients were delirious, with benzodiazepine use associated with increased incidence of delirium. These observations represent a significant departure from well-established pre-COVID best-practices in sedation: light targets, daily sedation interruption, and avoiding continuous benzodiazepine infusions whenever possible (Girard TD, et al. Lancet; 2008;371[9607]:126-34; Fraser GL, et al. Crit Care Med;2013 Sep;41[9 Suppl 1]:S30-8; Riker RR, et al. JAMA;2009;301[5]:489-99).

As COVID-19 case counts begin to improve in many of our communities, we have the opportunity to refocus on best sedation practices and build on a growing body of recent evidence. The MENDS2 trial, completed pre-COVID-19, assigned mechanically ventilated patients with sepsis to either propofol or dexmedetomidine and showed no difference in delirium or coma in this cohort of lightly sedated patients (Hughes CG, et al. N Engl J Med. 2021;384[15]:1424-36). Furthering this point, Olsen et al. found no difference in outcomes when mechanically ventilated patients were randomized to no sedation vs light sedation (Olsen HT, et al. N Engl J Med; 2020;382[12]:1103-11).

While the evidence surrounding sedation strategies in the critically ill continues to grow, one thing is certain: promoting lighter sedation targets and reengaging in sedation-related best practices following the COVID-19 pandemic will continue to play a vital role in improving both short and long-term outcomes for our critically ill patients.

Casey Cable, MD, MSc
Steering Committee Member

Kyle Stinehart, MD
Steering Committee Member
 

Home mechanical ventilation

How to initiate a chronic respiratory failure clinic

Noninvasive ventilation (NIV) is an established treatment for chronic hypercapnic respiratory failure from neuromuscular disorders, COPD, obesity hypoventilation syndrome (OHS), and restrictive thoracic disorders. Previously, hospital admission was considered essential for setup of chronic NIV but with advances in the modes of ventilation and remote monitoring, hospital admission has become less justifiable, especially in countries with centralized medical systems and presence of centers of excellence for home ventilation (Van Den Biggelaar RJM, et al. Chest. 2020;158[6]:2493-2501); Duiverman ML, et al. Thorax. 2020;75:244-52). In the United States, where centralized health care is atypical, management of NIV has been disparate with no clear consensus on practice patterns. Thus, we hope to provide some guidance toward the establishment of such clinics in the U.S.
 

Prior to developing an NIV clinic, establishing a referral source from neuromuscular, rehabilitation/spinal cord injury, bariatric surgery, and COPD programs is important. After this, collaboration with a respiratory therapist through durable medical equipment is essential to building a robust care team. These companies are also important for assisting in remote monitoring, providing overnight pulse oximetry/CO₂ monitoring, mask fitting, and airway clearance. Clinicians are encouraged to develop protocols for initiation and titration of NIV and mouthpiece ventilation. Clinics should provide spirometry, maximal inspiratory pressure, transcutaneous CO₂, and/or blood gas testing. Additionally, in this patient population, wheelchair scales are necessary. Clinical workflow should include a review of NIV downloads, identify asynchronies and troubleshoot it in timely and reliable manner (Blouet S, et al. Int J Chron Obstruct Pulmon Dis. 2018;13:2577-86). Lastly, effort should be made for an adequate assessment of the home situation including layout of home along with family support utilizing social worker and palliative care team. Due to patient mobility, we encourage continued availability of telehealth for these patients.

In summary, strong clinical infrastructure, a robust care team, and an efficient, secure, reliable telemonitoring system are key to provide better care to this vulnerable patient population.

Ashima S. Sahni, MD, MBBS, FCCP
NetWork Member

Amen Sergew, MD
Steering Committee Member

Interstitial and diffuse lung disease

Treatment for pulmonary hypertension secondary to interstitial lung disease

The development of pulmonary hypertension (PH) in patients with interstitial lung disease (ILD) (PH-ILD) is associated with increased supplemental oxygen requirements, reduced functional status, and decreased survival (King CS, et al. Chest. 2020;158[4]:1651).

An inhaled formulation of treprostinil (Tyvaso) is the first treatment option approved by the FDA for patients with PH-ILD, including those with idiopathic pulmonary fibrosis, connective tissue disease-associated ILD, and combined pulmonary fibrosis and emphysema. Approval was based on results from the INCREASE trial (Waxman A, et al. N Engl J Med. 2021;384[4]:325), a phase III multicenter, randomized, double-blinded study comparing the inhaled formulation to placebo in 326 patients over a 16-week period. Participants in the treatment arm were given up to 12 breaths of the formulation per session, four times per day. Subjects treated with this inhaled formulation met the primary study endpoint, an increase in 6-minute walk distance (6MWD) from baseline to week 16, walking 21 m farther than placebo-treated control subjects. Furthermore, patients receiving the new formulation had a decrease in NT-proBNP levels (compared with increases in the placebo arm) and a reduction in clinical worsening (23% of inhalation formulation-treated vs. 33% of placebo-treated subjects). This formulation of treprostinil was well-tolerated with a safety profile consistent with common prostacyclin-related adverse events, including cough, headache, dyspnea, dizziness, nausea, fatigue, and diarrhea. Its approval will dramatically alter the ILD treatment landscape. It now necessitates the use of PH screening in this patient population. However, care will need to be exercised in appropriate patient selection for treatment, using the study inclusion and exclusion criteria as a starting point. Appropriate use of this formulation will hopefully help mitigate the negative outcomes impacting patients with PH-ILD.

Rebecca Anna Gersten, MD
Adrian Shifren, MD
Steering Committee Members

Telemedicine has been proposed as a solution for an array of health care access problems over decades of gradual growth. The vast ramping up of telemedicine during the COVID-19 pandemic greatly expanded the evidence of its feasibility and what appears to be its inevitable incorporation into models of care, according to an update at the Health Policy and Advocacy Conference (HPAC) sponsored by the American College of Chest Physicians.

“The cat is out of the bag,” said Jaspal Singh, MD, FCCP, professor of medicine, Atrium Health, Charlotte, N.C. Due to changes in access and reimbursement to telemedicine driven by the pandemic, he said, “we now have permission to explore new models of care.”

Prior to February 2020, telemedicine was crawling forward at a leisurely pace, according to Dr. Singh. After March 2020, it broke into a run due to enormous demand and met by a rapid response from the U.S. Congress. The first of four legislative bills that directly or indirectly supported telemedicine was passed on March 6.

The Centers for Medicare and Medicaid Services (CMS) responded in kind, making modifications in a number of rules that removed obstacles to telehealth. One modification on April 6, for example, removed the requirement for a preexisting relationship between the clinician and patient, Dr. Singh said. The CMS also subsequently modified reimbursement policies in order to make telemedicine more tenable for physicians.

Given the risk of contagion from face-to-face encounters, telemedicine in the early days of the pandemic was not just attractive but the only practical and safe approach to medical care in many circumstances. Physicians and patients were anxious for health care that did not require in-office visits even though many critical issues for telemedicine, including its relative effectiveness, had not yet been fully evaluated.

Much has been learned regarding the feasibility and acceptability of telemedicine during the pandemic, but Dr. Singh noted that quality of care relative to in-person visits remains weakly supported for most indications. Indeed, he outlined a sizable list of incompletely resolved issues, including optimal payment models, management of privacy concerns, and how to balance advantages to disadvantages.

For patients and physicians, the strengths of telemedicine include greater convenience made possible by the elimination of travel and waiting rooms. For the health care system, it can include less infrastructure and overhead. For many physicians, telemedicine might be perceived as more efficient.

On the other hand, some patients might feel that a clinical encounter is incomplete without a physical examination even when the physician does not feel the physical examination is needed, according to Dr. Singh. He cited a survey suggesting nearly half of patients expressed concern about a lack of connection to health care providers following a virtual visit.

In the same 2020 National Poll on Healthy Aging 2020 survey conducted by the University of Michigan, 67% of respondents reported that the quality of care was not as good as that provided by in-patient visits, and 24% expressed concern about privacy. However, at the time the poll was taken in May 2020, experience with telemedicine among many of the respondents may have been limited. As telemedicine is integrated into routine care, perceptions might change as experience increases.

A distinction between telemedicine in routine care and telemedicine as a strategy to respond to a pandemic is important, Dr. Singh indicated. Dr. Singh was the lead author for a position paper on telemedicine for the diagnosis and treatment of sleep disorders from the American Academy of Sleep Medicine 5 years ago (J Clin Sleep Med. 2015;11:1187-98), but he acknowledged that models of care might differ when responding to abnormal surges in health care demand.

The surge in demand for COVID-19–related care engendered numerous innovative solutions. As examples, Dr. Singh recounted how a virtual hospital was created at his own institution. In a published study, 1,477 patients diagnosed with COVID19 over a 6-week period remained at home and received care in a virtual observation unit (VCU) or a virtual acute care unit (VACU) (Ann Intern Med. 2020;174:192-9). Only a small percentage required eventual hospital admission. In the VACU, patients were able to receive advanced care, including IV fluids and some form of respiratory support .

It is unclear how the COVID-19 pandemic will change telemedicine. Now, with declining cases of the infection, telemedicine is back to a walk after the sprint required during the height of the pandemic, according to Dr. Singh. However, Dr. Singh thinks many physicians and patients will have a different perception of telemedicine after the widespread exposure to this type of care.

In terms of the relative role of in-patient and virtual visits across indications, “we do not know how this will play out, but we will probably end up toggling between the two,” Dr. Singh said.

This is an area that is being followed closely by the CHEST Health Policy and Advocacy Committee, according to Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System. A member of that Committee and moderator of the session in which Dr. Singh spoke, Dr. Sarmiento called the effort to bring permanent coverage of telehealth services “the shared responsibility of every medical society engaged in advocacy.”

However, she cautioned that there might be intended and unintended consequences from telehealth that require analysis to develop policies that are in the best interests of effective care. She said, the “ACCP [CHEST], along with its sister societies, does have a role in supporting the evaluation of the impact of these changes on both patients and providers in the fields of pulmonary medicine, critical care, and sleep medicine.”

Dr. Singh reports a financial relationship with AstraZeneca. Dr. Sarmiento reports no relevant financial relationships.

Telemedicine has been proposed as a solution for an array of health care access problems over decades of gradual growth. The vast ramping up of telemedicine during the COVID-19 pandemic greatly expanded the evidence of its feasibility and what appears to be its inevitable incorporation into models of care, according to an update at the Health Policy and Advocacy Conference (HPAC) sponsored by the American College of Chest Physicians.

“The cat is out of the bag,” said Jaspal Singh, MD, FCCP, professor of medicine, Atrium Health, Charlotte, N.C. Due to changes in access and reimbursement to telemedicine driven by the pandemic, he said, “we now have permission to explore new models of care.”

Prior to February 2020, telemedicine was crawling forward at a leisurely pace, according to Dr. Singh. After March 2020, it broke into a run due to enormous demand and met by a rapid response from the U.S. Congress. The first of four legislative bills that directly or indirectly supported telemedicine was passed on March 6.

The Centers for Medicare and Medicaid Services (CMS) responded in kind, making modifications in a number of rules that removed obstacles to telehealth. One modification on April 6, for example, removed the requirement for a preexisting relationship between the clinician and patient, Dr. Singh said. The CMS also subsequently modified reimbursement policies in order to make telemedicine more tenable for physicians.

Given the risk of contagion from face-to-face encounters, telemedicine in the early days of the pandemic was not just attractive but the only practical and safe approach to medical care in many circumstances. Physicians and patients were anxious for health care that did not require in-office visits even though many critical issues for telemedicine, including its relative effectiveness, had not yet been fully evaluated.

Much has been learned regarding the feasibility and acceptability of telemedicine during the pandemic, but Dr. Singh noted that quality of care relative to in-person visits remains weakly supported for most indications. Indeed, he outlined a sizable list of incompletely resolved issues, including optimal payment models, management of privacy concerns, and how to balance advantages to disadvantages.

For patients and physicians, the strengths of telemedicine include greater convenience made possible by the elimination of travel and waiting rooms. For the health care system, it can include less infrastructure and overhead. For many physicians, telemedicine might be perceived as more efficient.

On the other hand, some patients might feel that a clinical encounter is incomplete without a physical examination even when the physician does not feel the physical examination is needed, according to Dr. Singh. He cited a survey suggesting nearly half of patients expressed concern about a lack of connection to health care providers following a virtual visit.

In the same 2020 National Poll on Healthy Aging 2020 survey conducted by the University of Michigan, 67% of respondents reported that the quality of care was not as good as that provided by in-patient visits, and 24% expressed concern about privacy. However, at the time the poll was taken in May 2020, experience with telemedicine among many of the respondents may have been limited. As telemedicine is integrated into routine care, perceptions might change as experience increases.

A distinction between telemedicine in routine care and telemedicine as a strategy to respond to a pandemic is important, Dr. Singh indicated. Dr. Singh was the lead author for a position paper on telemedicine for the diagnosis and treatment of sleep disorders from the American Academy of Sleep Medicine 5 years ago (J Clin Sleep Med. 2015;11:1187-98), but he acknowledged that models of care might differ when responding to abnormal surges in health care demand.

The surge in demand for COVID-19–related care engendered numerous innovative solutions. As examples, Dr. Singh recounted how a virtual hospital was created at his own institution. In a published study, 1,477 patients diagnosed with COVID19 over a 6-week period remained at home and received care in a virtual observation unit (VCU) or a virtual acute care unit (VACU) (Ann Intern Med. 2020;174:192-9). Only a small percentage required eventual hospital admission. In the VACU, patients were able to receive advanced care, including IV fluids and some form of respiratory support .

It is unclear how the COVID-19 pandemic will change telemedicine. Now, with declining cases of the infection, telemedicine is back to a walk after the sprint required during the height of the pandemic, according to Dr. Singh. However, Dr. Singh thinks many physicians and patients will have a different perception of telemedicine after the widespread exposure to this type of care.

In terms of the relative role of in-patient and virtual visits across indications, “we do not know how this will play out, but we will probably end up toggling between the two,” Dr. Singh said.

This is an area that is being followed closely by the CHEST Health Policy and Advocacy Committee, according to Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System. A member of that Committee and moderator of the session in which Dr. Singh spoke, Dr. Sarmiento called the effort to bring permanent coverage of telehealth services “the shared responsibility of every medical society engaged in advocacy.”

However, she cautioned that there might be intended and unintended consequences from telehealth that require analysis to develop policies that are in the best interests of effective care. She said, the “ACCP [CHEST], along with its sister societies, does have a role in supporting the evaluation of the impact of these changes on both patients and providers in the fields of pulmonary medicine, critical care, and sleep medicine.”

Dr. Singh reports a financial relationship with AstraZeneca. Dr. Sarmiento reports no relevant financial relationships.

Telemedicine has been proposed as a solution for an array of health care access problems over decades of gradual growth. The vast ramping up of telemedicine during the COVID-19 pandemic greatly expanded the evidence of its feasibility and what appears to be its inevitable incorporation into models of care, according to an update at the Health Policy and Advocacy Conference (HPAC) sponsored by the American College of Chest Physicians.

“The cat is out of the bag,” said Jaspal Singh, MD, FCCP, professor of medicine, Atrium Health, Charlotte, N.C. Due to changes in access and reimbursement to telemedicine driven by the pandemic, he said, “we now have permission to explore new models of care.”

Prior to February 2020, telemedicine was crawling forward at a leisurely pace, according to Dr. Singh. After March 2020, it broke into a run due to enormous demand and met by a rapid response from the U.S. Congress. The first of four legislative bills that directly or indirectly supported telemedicine was passed on March 6.

The Centers for Medicare and Medicaid Services (CMS) responded in kind, making modifications in a number of rules that removed obstacles to telehealth. One modification on April 6, for example, removed the requirement for a preexisting relationship between the clinician and patient, Dr. Singh said. The CMS also subsequently modified reimbursement policies in order to make telemedicine more tenable for physicians.

Given the risk of contagion from face-to-face encounters, telemedicine in the early days of the pandemic was not just attractive but the only practical and safe approach to medical care in many circumstances. Physicians and patients were anxious for health care that did not require in-office visits even though many critical issues for telemedicine, including its relative effectiveness, had not yet been fully evaluated.

Much has been learned regarding the feasibility and acceptability of telemedicine during the pandemic, but Dr. Singh noted that quality of care relative to in-person visits remains weakly supported for most indications. Indeed, he outlined a sizable list of incompletely resolved issues, including optimal payment models, management of privacy concerns, and how to balance advantages to disadvantages.

For patients and physicians, the strengths of telemedicine include greater convenience made possible by the elimination of travel and waiting rooms. For the health care system, it can include less infrastructure and overhead. For many physicians, telemedicine might be perceived as more efficient.

On the other hand, some patients might feel that a clinical encounter is incomplete without a physical examination even when the physician does not feel the physical examination is needed, according to Dr. Singh. He cited a survey suggesting nearly half of patients expressed concern about a lack of connection to health care providers following a virtual visit.

In the same 2020 National Poll on Healthy Aging 2020 survey conducted by the University of Michigan, 67% of respondents reported that the quality of care was not as good as that provided by in-patient visits, and 24% expressed concern about privacy. However, at the time the poll was taken in May 2020, experience with telemedicine among many of the respondents may have been limited. As telemedicine is integrated into routine care, perceptions might change as experience increases.

A distinction between telemedicine in routine care and telemedicine as a strategy to respond to a pandemic is important, Dr. Singh indicated. Dr. Singh was the lead author for a position paper on telemedicine for the diagnosis and treatment of sleep disorders from the American Academy of Sleep Medicine 5 years ago (J Clin Sleep Med. 2015;11:1187-98), but he acknowledged that models of care might differ when responding to abnormal surges in health care demand.

The surge in demand for COVID-19–related care engendered numerous innovative solutions. As examples, Dr. Singh recounted how a virtual hospital was created at his own institution. In a published study, 1,477 patients diagnosed with COVID19 over a 6-week period remained at home and received care in a virtual observation unit (VCU) or a virtual acute care unit (VACU) (Ann Intern Med. 2020;174:192-9). Only a small percentage required eventual hospital admission. In the VACU, patients were able to receive advanced care, including IV fluids and some form of respiratory support .

It is unclear how the COVID-19 pandemic will change telemedicine. Now, with declining cases of the infection, telemedicine is back to a walk after the sprint required during the height of the pandemic, according to Dr. Singh. However, Dr. Singh thinks many physicians and patients will have a different perception of telemedicine after the widespread exposure to this type of care.

In terms of the relative role of in-patient and virtual visits across indications, “we do not know how this will play out, but we will probably end up toggling between the two,” Dr. Singh said.

This is an area that is being followed closely by the CHEST Health Policy and Advocacy Committee, according to Kathleen Sarmiento, MD, FCCP, director, VISN 21 Sleep Clinical Resource Hub for the San Francisco VA Health Care System. A member of that Committee and moderator of the session in which Dr. Singh spoke, Dr. Sarmiento called the effort to bring permanent coverage of telehealth services “the shared responsibility of every medical society engaged in advocacy.”

However, she cautioned that there might be intended and unintended consequences from telehealth that require analysis to develop policies that are in the best interests of effective care. She said, the “ACCP [CHEST], along with its sister societies, does have a role in supporting the evaluation of the impact of these changes on both patients and providers in the fields of pulmonary medicine, critical care, and sleep medicine.”

Dr. Singh reports a financial relationship with AstraZeneca. Dr. Sarmiento reports no relevant financial relationships.

In last month’s Gastroenterology,  Vijay H. Shah, MD, and colleagues share a commentary on the esteemed career of this year’s Julius Friedenwald Medal recipient, Michael Camilleri, MD, of the Mayo Clinic in Rochester, Minnesota. Here are some fun facts about this year’s honoree:

• While growing up in Malta, he was influenced by a combination of his uncle, a kindly family physician, and by watching the shows Dr. Kildare and Marcus Welby, M.D., on a black-and-white television set during his childhood, which led Dr. Camilleri to commit to a career in medicine by the age of 8.
• Dr. Camilleri started his journey at the Mayo Clinic as a research fellow in 1983 conducting fundamental clinical research in GI motility.
• With 660 peer-reviewed original articles and 290 published invited reviews and editorial publications, Dr. Camilleri has redefined the understanding and treatment of disorders covering the entire GI tract from rumination syndrome to pelvic dyssynergia.
• Dr. Camilleri has mentored 79 postdoctoral fellows since he joined the faculty at Mayo Clinic 35 years ago.

Read more about Dr. Camilleri’s life and contribution to the GI community in this Gastroenterology commentary, written by his colleagues and friends, including Dr. Shah and Adil E. Bharucha, MBBS, MD; David A. Katzka, MD; and Gregory J. Gores, MD.

In last month’s Gastroenterology,  Vijay H. Shah, MD, and colleagues share a commentary on the esteemed career of this year’s Julius Friedenwald Medal recipient, Michael Camilleri, MD, of the Mayo Clinic in Rochester, Minnesota. Here are some fun facts about this year’s honoree:

• While growing up in Malta, he was influenced by a combination of his uncle, a kindly family physician, and by watching the shows Dr. Kildare and Marcus Welby, M.D., on a black-and-white television set during his childhood, which led Dr. Camilleri to commit to a career in medicine by the age of 8.
• Dr. Camilleri started his journey at the Mayo Clinic as a research fellow in 1983 conducting fundamental clinical research in GI motility.
• With 660 peer-reviewed original articles and 290 published invited reviews and editorial publications, Dr. Camilleri has redefined the understanding and treatment of disorders covering the entire GI tract from rumination syndrome to pelvic dyssynergia.
• Dr. Camilleri has mentored 79 postdoctoral fellows since he joined the faculty at Mayo Clinic 35 years ago.

Read more about Dr. Camilleri’s life and contribution to the GI community in this Gastroenterology commentary, written by his colleagues and friends, including Dr. Shah and Adil E. Bharucha, MBBS, MD; David A. Katzka, MD; and Gregory J. Gores, MD.

In last month’s Gastroenterology,  Vijay H. Shah, MD, and colleagues share a commentary on the esteemed career of this year’s Julius Friedenwald Medal recipient, Michael Camilleri, MD, of the Mayo Clinic in Rochester, Minnesota. Here are some fun facts about this year’s honoree:

• While growing up in Malta, he was influenced by a combination of his uncle, a kindly family physician, and by watching the shows Dr. Kildare and Marcus Welby, M.D., on a black-and-white television set during his childhood, which led Dr. Camilleri to commit to a career in medicine by the age of 8.
• Dr. Camilleri started his journey at the Mayo Clinic as a research fellow in 1983 conducting fundamental clinical research in GI motility.
• With 660 peer-reviewed original articles and 290 published invited reviews and editorial publications, Dr. Camilleri has redefined the understanding and treatment of disorders covering the entire GI tract from rumination syndrome to pelvic dyssynergia.
• Dr. Camilleri has mentored 79 postdoctoral fellows since he joined the faculty at Mayo Clinic 35 years ago.

Read more about Dr. Camilleri’s life and contribution to the GI community in this Gastroenterology commentary, written by his colleagues and friends, including Dr. Shah and Adil E. Bharucha, MBBS, MD; David A. Katzka, MD; and Gregory J. Gores, MD.

American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy issued a statement of support that also notes our Multi-Society Task Force on Colorectal Cancer is finalizing our own recommendation to start screening at 45 years of age as well. 

Incoming AGA President John M. Inadomi, MD, AGAF, notes that, “We expect this important change to save lives and improve the health of the U.S. population.” 

AGA fully supports the decision of the U.S. Preventive Services Task Force to reduce the age at which to initiate screening among individuals at average risk for development of colorectal cancer to 45 years. This decision harmonizes the recommendations between the major U.S. screening guidelines including the American Cancer Society and American College of Physicians.  

“The analysis by the USPSTF is timely and incredibly helpful to population health and to gastroenterologists and other providers,” says Bishr Omary, MD, PhD, AGAF, president of AGA. “We now have clear guidance to start colorectal cancer screening at age 45 for those with average risk and discontinue screening after age 85.”

American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy issued a statement of support that also notes our Multi-Society Task Force on Colorectal Cancer is finalizing our own recommendation to start screening at 45 years of age as well. 

Incoming AGA President John M. Inadomi, MD, AGAF, notes that, “We expect this important change to save lives and improve the health of the U.S. population.” 

AGA fully supports the decision of the U.S. Preventive Services Task Force to reduce the age at which to initiate screening among individuals at average risk for development of colorectal cancer to 45 years. This decision harmonizes the recommendations between the major U.S. screening guidelines including the American Cancer Society and American College of Physicians.  

“The analysis by the USPSTF is timely and incredibly helpful to population health and to gastroenterologists and other providers,” says Bishr Omary, MD, PhD, AGAF, president of AGA. “We now have clear guidance to start colorectal cancer screening at age 45 for those with average risk and discontinue screening after age 85.”

American Gastroenterological Association, American College of Gastroenterology, and American Society for Gastrointestinal Endoscopy issued a statement of support that also notes our Multi-Society Task Force on Colorectal Cancer is finalizing our own recommendation to start screening at 45 years of age as well. 

Incoming AGA President John M. Inadomi, MD, AGAF, notes that, “We expect this important change to save lives and improve the health of the U.S. population.” 

AGA fully supports the decision of the U.S. Preventive Services Task Force to reduce the age at which to initiate screening among individuals at average risk for development of colorectal cancer to 45 years. This decision harmonizes the recommendations between the major U.S. screening guidelines including the American Cancer Society and American College of Physicians.  

“The analysis by the USPSTF is timely and incredibly helpful to population health and to gastroenterologists and other providers,” says Bishr Omary, MD, PhD, AGAF, president of AGA. “We now have clear guidance to start colorectal cancer screening at age 45 for those with average risk and discontinue screening after age 85.”

We are pleased to announce that the AGA Research Foundation’s research awards cycle is now open.

The cycle begins with our two specialty awards focused on digestive and gastric cancers – applications are due on July 21. 

AGA–Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer: One $40,000 award supports an early career investigator who holds a career development award devoted to digestive cancer research.

AGA–R. Robert & Sally Funderburg Research Award in Gastric Cancer One $100,000 award supports an established investigator working on novel approaches in gastric cancer research.

In addition to our usual awards portfolio focused on a broad range of digestive diseases, we have established several new awards that will fund research focused on health and health care disparities. Click on the links below to learn more about each award and application requirements. 

• Pilot Research Awards: Currently accepting applications
• Research Scholar Awards: Open Aug. 12 

We are pleased to announce that the AGA Research Foundation’s research awards cycle is now open.

The cycle begins with our two specialty awards focused on digestive and gastric cancers – applications are due on July 21. 

AGA–Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer: One $40,000 award supports an early career investigator who holds a career development award devoted to digestive cancer research.

AGA–R. Robert & Sally Funderburg Research Award in Gastric Cancer One $100,000 award supports an established investigator working on novel approaches in gastric cancer research.

In addition to our usual awards portfolio focused on a broad range of digestive diseases, we have established several new awards that will fund research focused on health and health care disparities. Click on the links below to learn more about each award and application requirements. 

• Pilot Research Awards: Currently accepting applications
• Research Scholar Awards: Open Aug. 12 

We are pleased to announce that the AGA Research Foundation’s research awards cycle is now open.

The cycle begins with our two specialty awards focused on digestive and gastric cancers – applications are due on July 21. 

AGA–Caroline Craig Augustyn & Damian Augustyn Award in Digestive Cancer: One $40,000 award supports an early career investigator who holds a career development award devoted to digestive cancer research.

AGA–R. Robert & Sally Funderburg Research Award in Gastric Cancer One $100,000 award supports an established investigator working on novel approaches in gastric cancer research.

In addition to our usual awards portfolio focused on a broad range of digestive diseases, we have established several new awards that will fund research focused on health and health care disparities. Click on the links below to learn more about each award and application requirements. 

• Pilot Research Awards: Currently accepting applications
• Research Scholar Awards: Open Aug. 12 

If you want to make a lasting impact at the AGA Research Foundation, one of the easiest ways is to name us as a beneficiary of one of your assets, such as your retirement plan, life insurance policy, bank account, or donor-advised fund.

When you do, don’t forget to notify us of your decisions. Many charities and individuals aren’t aware that they have been named to receive a gift. Informing them helps preserve your intentions and ensures that your beneficiaries are able to follow your wishes.
 

Steps to protect the people and charities you love

• Review your beneficiary designations periodically because circumstances change throughout your lifetime.
• Alert your beneficiaries that you have a life insurance policy or have named them as beneficiaries of a retirement plan.
• Share the location and details of the policy or plan with your beneficiaries.

As you update your beneficiary designations, consider making a gift of a life insurance policy or retirement plan to the AGA Research Foundation so that we can continue to progress with our mission. Then let us know about your decision so that we can carry out your wishes as intended and thank you for your gift.
 

We want to hear from you

If you have already named the AGA Research Foundation as a beneficiary of a life insurance policy or retirement plan assets, please contact us at [email protected] today. If you are still creating your estate plan, we would be happy to answer any questions you may have about making this type of gift.

If you want to make a lasting impact at the AGA Research Foundation, one of the easiest ways is to name us as a beneficiary of one of your assets, such as your retirement plan, life insurance policy, bank account, or donor-advised fund.

When you do, don’t forget to notify us of your decisions. Many charities and individuals aren’t aware that they have been named to receive a gift. Informing them helps preserve your intentions and ensures that your beneficiaries are able to follow your wishes.
 

Steps to protect the people and charities you love

• Review your beneficiary designations periodically because circumstances change throughout your lifetime.
• Alert your beneficiaries that you have a life insurance policy or have named them as beneficiaries of a retirement plan.
• Share the location and details of the policy or plan with your beneficiaries.

As you update your beneficiary designations, consider making a gift of a life insurance policy or retirement plan to the AGA Research Foundation so that we can continue to progress with our mission. Then let us know about your decision so that we can carry out your wishes as intended and thank you for your gift.
 

We want to hear from you

If you have already named the AGA Research Foundation as a beneficiary of a life insurance policy or retirement plan assets, please contact us at [email protected] today. If you are still creating your estate plan, we would be happy to answer any questions you may have about making this type of gift.

If you want to make a lasting impact at the AGA Research Foundation, one of the easiest ways is to name us as a beneficiary of one of your assets, such as your retirement plan, life insurance policy, bank account, or donor-advised fund.

When you do, don’t forget to notify us of your decisions. Many charities and individuals aren’t aware that they have been named to receive a gift. Informing them helps preserve your intentions and ensures that your beneficiaries are able to follow your wishes.
 

Steps to protect the people and charities you love

• Review your beneficiary designations periodically because circumstances change throughout your lifetime.
• Alert your beneficiaries that you have a life insurance policy or have named them as beneficiaries of a retirement plan.
• Share the location and details of the policy or plan with your beneficiaries.

As you update your beneficiary designations, consider making a gift of a life insurance policy or retirement plan to the AGA Research Foundation so that we can continue to progress with our mission. Then let us know about your decision so that we can carry out your wishes as intended and thank you for your gift.
 

We want to hear from you

If you have already named the AGA Research Foundation as a beneficiary of a life insurance policy or retirement plan assets, please contact us at [email protected] today. If you are still creating your estate plan, we would be happy to answer any questions you may have about making this type of gift.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

From Rafael Ching Companioni, MD: Malnutrition, elevated liver enzymes, anemia, and malabsorption

“Early 30 year-old female who was initially referred to GI in December 2020 for abnormal liver enzymes ALT 263, AST 114, alk phosp 212, albumin 3.2, bili [within normal limits]. At that time, she reports some diarrhea, few episodes of diarrhea per day, diffuse abdominal pain, ~20 LBs weight loss. She denied herbal medications, OTC medications or other medications. Last travel was 2 years ago to England. No history of anorexia nervosa or bulimia. On examination, cachexia and extremity edema. She has iron deficiency anemia and reactive thrombocytosis. Her initial lipid panel in November 2020, the lipid panel shows total cholesterol 208, LDL 113, triglycerides 227.

“She is still losing weight: 20 lbs from Feb 2021. The liver enzymes elevation resolved. She has anemia, malnutrition and malabsorption. I recommended gluten free diet, MVI, iron pills, protein bars. I had ordered scleroderma workup and SIBO tests today. I am planning to do MRE.”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/24416.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

From Rafael Ching Companioni, MD: Malnutrition, elevated liver enzymes, anemia, and malabsorption

“Early 30 year-old female who was initially referred to GI in December 2020 for abnormal liver enzymes ALT 263, AST 114, alk phosp 212, albumin 3.2, bili [within normal limits]. At that time, she reports some diarrhea, few episodes of diarrhea per day, diffuse abdominal pain, ~20 LBs weight loss. She denied herbal medications, OTC medications or other medications. Last travel was 2 years ago to England. No history of anorexia nervosa or bulimia. On examination, cachexia and extremity edema. She has iron deficiency anemia and reactive thrombocytosis. Her initial lipid panel in November 2020, the lipid panel shows total cholesterol 208, LDL 113, triglycerides 227.

“She is still losing weight: 20 lbs from Feb 2021. The liver enzymes elevation resolved. She has anemia, malnutrition and malabsorption. I recommended gluten free diet, MVI, iron pills, protein bars. I had ordered scleroderma workup and SIBO tests today. I am planning to do MRE.”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/24416.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community (https://community.gastro.org) to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. Here’s a preview of a recent popular clinical discussion:  

From Rafael Ching Companioni, MD: Malnutrition, elevated liver enzymes, anemia, and malabsorption

“Early 30 year-old female who was initially referred to GI in December 2020 for abnormal liver enzymes ALT 263, AST 114, alk phosp 212, albumin 3.2, bili [within normal limits]. At that time, she reports some diarrhea, few episodes of diarrhea per day, diffuse abdominal pain, ~20 LBs weight loss. She denied herbal medications, OTC medications or other medications. Last travel was 2 years ago to England. No history of anorexia nervosa or bulimia. On examination, cachexia and extremity edema. She has iron deficiency anemia and reactive thrombocytosis. Her initial lipid panel in November 2020, the lipid panel shows total cholesterol 208, LDL 113, triglycerides 227.

“She is still losing weight: 20 lbs from Feb 2021. The liver enzymes elevation resolved. She has anemia, malnutrition and malabsorption. I recommended gluten free diet, MVI, iron pills, protein bars. I had ordered scleroderma workup and SIBO tests today. I am planning to do MRE.”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/24416.

In 2020, the world was rocked by a global pandemic; our response was to provide COVID-19 community service grants to some of the most vulnerable populations. The CHEST Foundation, with support from donors and the Feldman Family Foundation, was able to provide $120,000 to support communities in need of essential items. Personal protective equipment, cleaning supplies, emergency food purchases, and more were purchased with these grants to aid communities disproportionately affected by the pandemic.

Without you, these grants would not have been possible. CHEST’s NetWorks worked all summer of 2020 to raise funds to make a tangible impact on at-risk communities in the wake of the pandemic. We’re counting on you again to help us raise money this year for more community service grants.

The NetWorks Challenge 2021 will fund community-based projects focused on health disparities and disproportionately underserved communities. Get ready to compete in the challenge to directly make an impact on those who could otherwise not afford access to health care.

This offering, dubbed Rita’s Fund, will award $2,500 to $10,000 to community-based projects providing resources to individuals to drastically change their quality of life. Medical equipment, transportation, and technology access aren’t available to all, but through this grant, they will be provided to those who need it most.

Rita’s Fund originated after hearing the story of Rita Castro during the virtual Listening Tour and our initiative to listen and identify barriers to trust, access, and equity in our most underserved communities. The CHEST Foundation was inspired by her story, as she was fighting a rapidly progressing lung condition with no support. Through donations she was able to receive the care she needed, and her diagnosis improved.

Your work during the NetWorks Challenge will help fund grants through Rita’s Fund and travel grants to attend this year’s CHEST Annual Meeting. We need your help to ensure individuals like Rita have access to better health and resources they can trust.

To learn more about this initiative and this year’s NetWorks Challenge, visit the CHEST Foundation’s website at https://foundation.chestnet.org.

In 2020, the world was rocked by a global pandemic; our response was to provide COVID-19 community service grants to some of the most vulnerable populations. The CHEST Foundation, with support from donors and the Feldman Family Foundation, was able to provide $120,000 to support communities in need of essential items. Personal protective equipment, cleaning supplies, emergency food purchases, and more were purchased with these grants to aid communities disproportionately affected by the pandemic.

Without you, these grants would not have been possible. CHEST’s NetWorks worked all summer of 2020 to raise funds to make a tangible impact on at-risk communities in the wake of the pandemic. We’re counting on you again to help us raise money this year for more community service grants.

The NetWorks Challenge 2021 will fund community-based projects focused on health disparities and disproportionately underserved communities. Get ready to compete in the challenge to directly make an impact on those who could otherwise not afford access to health care.

This offering, dubbed Rita’s Fund, will award $2,500 to $10,000 to community-based projects providing resources to individuals to drastically change their quality of life. Medical equipment, transportation, and technology access aren’t available to all, but through this grant, they will be provided to those who need it most.

Rita’s Fund originated after hearing the story of Rita Castro during the virtual Listening Tour and our initiative to listen and identify barriers to trust, access, and equity in our most underserved communities. The CHEST Foundation was inspired by her story, as she was fighting a rapidly progressing lung condition with no support. Through donations she was able to receive the care she needed, and her diagnosis improved.

Your work during the NetWorks Challenge will help fund grants through Rita’s Fund and travel grants to attend this year’s CHEST Annual Meeting. We need your help to ensure individuals like Rita have access to better health and resources they can trust.

To learn more about this initiative and this year’s NetWorks Challenge, visit the CHEST Foundation’s website at https://foundation.chestnet.org.

In 2020, the world was rocked by a global pandemic; our response was to provide COVID-19 community service grants to some of the most vulnerable populations. The CHEST Foundation, with support from donors and the Feldman Family Foundation, was able to provide $120,000 to support communities in need of essential items. Personal protective equipment, cleaning supplies, emergency food purchases, and more were purchased with these grants to aid communities disproportionately affected by the pandemic.

Without you, these grants would not have been possible. CHEST’s NetWorks worked all summer of 2020 to raise funds to make a tangible impact on at-risk communities in the wake of the pandemic. We’re counting on you again to help us raise money this year for more community service grants.

The NetWorks Challenge 2021 will fund community-based projects focused on health disparities and disproportionately underserved communities. Get ready to compete in the challenge to directly make an impact on those who could otherwise not afford access to health care.

This offering, dubbed Rita’s Fund, will award $2,500 to $10,000 to community-based projects providing resources to individuals to drastically change their quality of life. Medical equipment, transportation, and technology access aren’t available to all, but through this grant, they will be provided to those who need it most.

Rita’s Fund originated after hearing the story of Rita Castro during the virtual Listening Tour and our initiative to listen and identify barriers to trust, access, and equity in our most underserved communities. The CHEST Foundation was inspired by her story, as she was fighting a rapidly progressing lung condition with no support. Through donations she was able to receive the care she needed, and her diagnosis improved.

Your work during the NetWorks Challenge will help fund grants through Rita’s Fund and travel grants to attend this year’s CHEST Annual Meeting. We need your help to ensure individuals like Rita have access to better health and resources they can trust.

To learn more about this initiative and this year’s NetWorks Challenge, visit the CHEST Foundation’s website at https://foundation.chestnet.org.

Current guideline recommendations for fluid resuscitation in sepsis patients calls for an initial crystalloid fluid bolus of at least 30 mL/kg (Rhodes, et al. Intensive Care Med. 2017;43[3]:304-77) For fluid management beyond this initial bolus, recommendations had previously called for using early goal-directed therapy (EGDT) with central venous pressure (CVP) and central venous oxygen saturation to guide the use of IV fluids, vasopressors, transfusions, and dobutamine, based on the results of one single-center study that found an improvement in mortality using EGDT as compared with standard therapy.

The triad of sepsis studies

In the following years, multiple concerns were raised regarding the generalizability of this study. Three large multicenter trials were conducted in multiple countries to test the recommendations for EGDT.

PROMISE: ProMISe was a 1,260-patient randomized trial comparing the impact of EGDT vs usual care on 90-day all-cause mortality in patients with early septic shock at 56 hospitals in England. There was no significant difference in the primary study endpoint with 90-day mortality rates of 29.5% and 29.2% (RR: 1.01, 95% CI: 0.85-1.20, P =.90) (Mouncey, et al. N Engl J Med. 2015;372[14]:1301-11).

PROCESS: ProCESS was a 1,351-patient randomized trial comparing the impact of protocol-based EGDT, protocol-based standard of care, and usual care on 60 day in-hospital mortality in patients with early septic shock at 31 hospitals in the United States. There was no significant difference in the primary study endpoint with 60-day mortality rates of 21.0%, 18.2%, and 18.9% (P = .83) or in the secondary outcome of 90-day mortality with rates of 31.9%, 30.8%, and 33.7% (P = .66) (ProCESS Investigators, et al. N Engl J Med. 2014;370[18]:1683-93).

ARISE: ARISE was a 1,600-patient randomized trial comparing the impact of EGDT vs usual care on 90-day all-cause mortality in patients with early septic shock at 51 hospitals in New Zealand and Australia. There was no significant difference in the primary study end point with 90-day mortality rates of 18.6% and 18.8% (RR: 0.98, 95% CI: 0.80-1.21, P = .90). There were also no significant differences in 28-day or in-hospital mortality, duration of organ support, or length of hospital stay (ARISE Investigators, et al. N Engl J Med. 2014;371[16]:1496-506).

In summary, all three “triad” trials found no improvement with EGDT over usual care (Rowan, et al. N Engl J Med. 2017;376[23]:2223-34) calling into question the recommended methods of universally protocolized approaches to fluid and pressor resuscitation. Probable reasons for why structured EGDT was ineffective at improving outcomes over usual care in the “triad” trials was that (a) liberal fluid volume administration was the “usual care” in most enrolled patients and (b) that macrocirculatory hemodynamics, such as BP, and static intravascular pressures such as CVP and pulmonary arterial wedge pressure are poor correlates and predictors of effective circulatory volumes and the presence of fluid responsiveness.

Counterintuitively, in situations of central hypovolemia, peripheral sympathetic activity remains high in many patients while stroke volume decreases. This provides insight into why some patients appear not to benefit from fluid administration as peripheral arterial pressure may be maintained despite low central filling pressure (Convertino VA, et al. Auton Neurosci. 2004;111[2]:127-34). Many patients with sepsis and septic shock initially present in an undifferentiated state and empiric treatment decisions regarding fluid and pressor treatments are then misaligned to functional physiological status.

Novel methods and approaches are needed to differentiate these patients and provide appropriate, physiologically guided fluid resuscitation. Dynamic measurement of stroke volume (SV) after a passive leg raise (PLR) or a small IV fluid challenge is an emerging method for determining fluid responsiveness. Evidence suggests that the use of SV-guided resuscitation can reduce net fluid balance, ICU length of stay, risk of mechanical ventilation, time on vasopressors, and risk of renal replacement therapy.(Latham HE, et al. J Crit Care. 2017;42:42-6).

In addition to the lack of efficacy from administering fluid to nonfluid responsive patients, there remains a risk of over-resuscitation from excessive fluid administration. Excessive fluid administration causes hypervolemia and is associated with a variety of negative patient outcomes including tissue edema, organ dysfunction, increased ICU length of stay, prolonged ventilator dependence, and higher mortality rates (Tigabu BM, et al. J Crit Care. 2018;48:153-9). Further, unnecessary initial fluid administration necessitates a “de-resuscitative” phase that can prolong hospital stay and is associated with amplification of sepsis-associated organ failures. Specifically, a 2017 analysis of hospital discharge data found that large volume fluid resuscitation in sepsis patients during the first 24 hours of care was associated with higher rates of hospital mortality than was predicted for patients’ disease severity (Mansoori JN, et al. Crit Care. 2020;24[1]:25).
 

The FRESH trial

The Fluid Response Evaluation in Sepsis Hypotension and Shock (FRESH) trial was a prospective, randomized clinical trial in adults with septic shock comparing PLR-guided SV responsiveness (intervention) as a guide for fluid management with usual care. Patients presented to the ER with sepsis-associated hypotension and anticipated ICU admission. In the intervention arm, patients were assessed for fluid responsiveness (FR) before any clinically driven fluid bolus or increase in vasopressors. If a patient’s stroke volume increased by ≥10% in response to a PLR, they were considered fluid responsive and fluid was recommended as the first therapy. If a patient’s stroke volume increased by <10% then the patient was considered not to be FR and vasopressors were recommended as first-line therapy. The control arm received usual care. The primary end point was the difference in positive fluid balance at the first of either 72 hours or ICU discharge. Patients had received ~2.3 L of crystalloid fluid prior to randomization (~3.5 h from initial presentation), in keeping with 30 mL/kg recommendations. Patients treated with the PLR-guided fluid and pressor protocol had a significant lower net fluid balance (1.37 L (95% CI: 2.53-0.21, P = .021) at 72 hours or ICU discharge. In addition, the intervention group experienced significantly less frequent requirement for renal replacement therapy with a difference of 12.4% (95% CI: 27%-1%, P = .042) as well as a decreased requirement for ventilator use with a difference of 16.42% (95% CI: 33%-0%, P = .044) (Douglas IS, et al. Chest. 2020;158[4]:1431-45).

FRESH demonstrated that PLR-guided FR drove lower fluid balance in patients with septic shock who present to the ER with sepsis and creates a paradigm for future management of fluid and pressor resuscitation beyond the initial 30 mL/kg bolus. Functional evaluation for lack of FR adequately identifies a group of patients with sepsis-associated hypotension who are unlikely to benefit from additional IV fluids to establish hemodynamically stability. It facilitated physiologically informed treatment decisions for the individual patient at a specific moment in their course of treatment as opposed to relying on static measurements and goals that may ultimately not be indicative of fluid responsiveness and circulatory effectiveness. This could reduce the likelihood of fluid overload and associated organ failure and, thus, improve patient outcomes.

Microcirculatory function is significantly impacted by sepsis with a decline in capillary density and inappropriate vasodilation/constriction resulting in insufficient tissue and organ perfusion and increased oxidative stress. Such dysfunction has been found to be associated with worsened patient outcomes, including mortality. However, microcirculatory function does not correlate well with traditionally used macrohemodynamic assessments and treating to improve macrohemodynamic values does not ensure that microcirculation will improve (Charlton M, et al. J Intensive Care Soc. 2017;18(3):221-7).

Ongoing studies are exploring if dynamic fluid-guided resuscitation has the potential to improve survival in sepsis by providing insight into whether the administration of fluid will impact the microcirculation and subsequent organ perfusion of the patient.

Future directions include expanding the dynamic treatment algorithm into other settings, such as rapid response calls, or other patient populations, including those initially presenting with undifferentiated hypotension. While FRESH was not sufficiently powered to detect differences in mortality, there are currently multiple large studies being conducted aimed at determining the impact of a restricted fluid and early vasopressor strategy as compared with a large initial IV fluid bolus on mortality. The results of these studies could be used to determine if the results of FRESH will translate into patient survival outcomes.
 

Current guideline recommendations for fluid resuscitation in sepsis patients calls for an initial crystalloid fluid bolus of at least 30 mL/kg (Rhodes, et al. Intensive Care Med. 2017;43[3]:304-77) For fluid management beyond this initial bolus, recommendations had previously called for using early goal-directed therapy (EGDT) with central venous pressure (CVP) and central venous oxygen saturation to guide the use of IV fluids, vasopressors, transfusions, and dobutamine, based on the results of one single-center study that found an improvement in mortality using EGDT as compared with standard therapy.

The triad of sepsis studies

In the following years, multiple concerns were raised regarding the generalizability of this study. Three large multicenter trials were conducted in multiple countries to test the recommendations for EGDT.

PROMISE: ProMISe was a 1,260-patient randomized trial comparing the impact of EGDT vs usual care on 90-day all-cause mortality in patients with early septic shock at 56 hospitals in England. There was no significant difference in the primary study endpoint with 90-day mortality rates of 29.5% and 29.2% (RR: 1.01, 95% CI: 0.85-1.20, P =.90) (Mouncey, et al. N Engl J Med. 2015;372[14]:1301-11).

PROCESS: ProCESS was a 1,351-patient randomized trial comparing the impact of protocol-based EGDT, protocol-based standard of care, and usual care on 60 day in-hospital mortality in patients with early septic shock at 31 hospitals in the United States. There was no significant difference in the primary study endpoint with 60-day mortality rates of 21.0%, 18.2%, and 18.9% (P = .83) or in the secondary outcome of 90-day mortality with rates of 31.9%, 30.8%, and 33.7% (P = .66) (ProCESS Investigators, et al. N Engl J Med. 2014;370[18]:1683-93).

ARISE: ARISE was a 1,600-patient randomized trial comparing the impact of EGDT vs usual care on 90-day all-cause mortality in patients with early septic shock at 51 hospitals in New Zealand and Australia. There was no significant difference in the primary study end point with 90-day mortality rates of 18.6% and 18.8% (RR: 0.98, 95% CI: 0.80-1.21, P = .90). There were also no significant differences in 28-day or in-hospital mortality, duration of organ support, or length of hospital stay (ARISE Investigators, et al. N Engl J Med. 2014;371[16]:1496-506).

In summary, all three “triad” trials found no improvement with EGDT over usual care (Rowan, et al. N Engl J Med. 2017;376[23]:2223-34) calling into question the recommended methods of universally protocolized approaches to fluid and pressor resuscitation. Probable reasons for why structured EGDT was ineffective at improving outcomes over usual care in the “triad” trials was that (a) liberal fluid volume administration was the “usual care” in most enrolled patients and (b) that macrocirculatory hemodynamics, such as BP, and static intravascular pressures such as CVP and pulmonary arterial wedge pressure are poor correlates and predictors of effective circulatory volumes and the presence of fluid responsiveness.

Counterintuitively, in situations of central hypovolemia, peripheral sympathetic activity remains high in many patients while stroke volume decreases. This provides insight into why some patients appear not to benefit from fluid administration as peripheral arterial pressure may be maintained despite low central filling pressure (Convertino VA, et al. Auton Neurosci. 2004;111[2]:127-34). Many patients with sepsis and septic shock initially present in an undifferentiated state and empiric treatment decisions regarding fluid and pressor treatments are then misaligned to functional physiological status.

Novel methods and approaches are needed to differentiate these patients and provide appropriate, physiologically guided fluid resuscitation. Dynamic measurement of stroke volume (SV) after a passive leg raise (PLR) or a small IV fluid challenge is an emerging method for determining fluid responsiveness. Evidence suggests that the use of SV-guided resuscitation can reduce net fluid balance, ICU length of stay, risk of mechanical ventilation, time on vasopressors, and risk of renal replacement therapy.(Latham HE, et al. J Crit Care. 2017;42:42-6).

In addition to the lack of efficacy from administering fluid to nonfluid responsive patients, there remains a risk of over-resuscitation from excessive fluid administration. Excessive fluid administration causes hypervolemia and is associated with a variety of negative patient outcomes including tissue edema, organ dysfunction, increased ICU length of stay, prolonged ventilator dependence, and higher mortality rates (Tigabu BM, et al. J Crit Care. 2018;48:153-9). Further, unnecessary initial fluid administration necessitates a “de-resuscitative” phase that can prolong hospital stay and is associated with amplification of sepsis-associated organ failures. Specifically, a 2017 analysis of hospital discharge data found that large volume fluid resuscitation in sepsis patients during the first 24 hours of care was associated with higher rates of hospital mortality than was predicted for patients’ disease severity (Mansoori JN, et al. Crit Care. 2020;24[1]:25).
 

The FRESH trial

The Fluid Response Evaluation in Sepsis Hypotension and Shock (FRESH) trial was a prospective, randomized clinical trial in adults with septic shock comparing PLR-guided SV responsiveness (intervention) as a guide for fluid management with usual care. Patients presented to the ER with sepsis-associated hypotension and anticipated ICU admission. In the intervention arm, patients were assessed for fluid responsiveness (FR) before any clinically driven fluid bolus or increase in vasopressors. If a patient’s stroke volume increased by ≥10% in response to a PLR, they were considered fluid responsive and fluid was recommended as the first therapy. If a patient’s stroke volume increased by <10% then the patient was considered not to be FR and vasopressors were recommended as first-line therapy. The control arm received usual care. The primary end point was the difference in positive fluid balance at the first of either 72 hours or ICU discharge. Patients had received ~2.3 L of crystalloid fluid prior to randomization (~3.5 h from initial presentation), in keeping with 30 mL/kg recommendations. Patients treated with the PLR-guided fluid and pressor protocol had a significant lower net fluid balance (1.37 L (95% CI: 2.53-0.21, P = .021) at 72 hours or ICU discharge. In addition, the intervention group experienced significantly less frequent requirement for renal replacement therapy with a difference of 12.4% (95% CI: 27%-1%, P = .042) as well as a decreased requirement for ventilator use with a difference of 16.42% (95% CI: 33%-0%, P = .044) (Douglas IS, et al. Chest. 2020;158[4]:1431-45).

FRESH demonstrated that PLR-guided FR drove lower fluid balance in patients with septic shock who present to the ER with sepsis and creates a paradigm for future management of fluid and pressor resuscitation beyond the initial 30 mL/kg bolus. Functional evaluation for lack of FR adequately identifies a group of patients with sepsis-associated hypotension who are unlikely to benefit from additional IV fluids to establish hemodynamically stability. It facilitated physiologically informed treatment decisions for the individual patient at a specific moment in their course of treatment as opposed to relying on static measurements and goals that may ultimately not be indicative of fluid responsiveness and circulatory effectiveness. This could reduce the likelihood of fluid overload and associated organ failure and, thus, improve patient outcomes.

Microcirculatory function is significantly impacted by sepsis with a decline in capillary density and inappropriate vasodilation/constriction resulting in insufficient tissue and organ perfusion and increased oxidative stress. Such dysfunction has been found to be associated with worsened patient outcomes, including mortality. However, microcirculatory function does not correlate well with traditionally used macrohemodynamic assessments and treating to improve macrohemodynamic values does not ensure that microcirculation will improve (Charlton M, et al. J Intensive Care Soc. 2017;18(3):221-7).

Ongoing studies are exploring if dynamic fluid-guided resuscitation has the potential to improve survival in sepsis by providing insight into whether the administration of fluid will impact the microcirculation and subsequent organ perfusion of the patient.

Future directions include expanding the dynamic treatment algorithm into other settings, such as rapid response calls, or other patient populations, including those initially presenting with undifferentiated hypotension. While FRESH was not sufficiently powered to detect differences in mortality, there are currently multiple large studies being conducted aimed at determining the impact of a restricted fluid and early vasopressor strategy as compared with a large initial IV fluid bolus on mortality. The results of these studies could be used to determine if the results of FRESH will translate into patient survival outcomes.
 

Current guideline recommendations for fluid resuscitation in sepsis patients calls for an initial crystalloid fluid bolus of at least 30 mL/kg (Rhodes, et al. Intensive Care Med. 2017;43[3]:304-77) For fluid management beyond this initial bolus, recommendations had previously called for using early goal-directed therapy (EGDT) with central venous pressure (CVP) and central venous oxygen saturation to guide the use of IV fluids, vasopressors, transfusions, and dobutamine, based on the results of one single-center study that found an improvement in mortality using EGDT as compared with standard therapy.

The triad of sepsis studies

In the following years, multiple concerns were raised regarding the generalizability of this study. Three large multicenter trials were conducted in multiple countries to test the recommendations for EGDT.

PROMISE: ProMISe was a 1,260-patient randomized trial comparing the impact of EGDT vs usual care on 90-day all-cause mortality in patients with early septic shock at 56 hospitals in England. There was no significant difference in the primary study endpoint with 90-day mortality rates of 29.5% and 29.2% (RR: 1.01, 95% CI: 0.85-1.20, P =.90) (Mouncey, et al. N Engl J Med. 2015;372[14]:1301-11).

PROCESS: ProCESS was a 1,351-patient randomized trial comparing the impact of protocol-based EGDT, protocol-based standard of care, and usual care on 60 day in-hospital mortality in patients with early septic shock at 31 hospitals in the United States. There was no significant difference in the primary study endpoint with 60-day mortality rates of 21.0%, 18.2%, and 18.9% (P = .83) or in the secondary outcome of 90-day mortality with rates of 31.9%, 30.8%, and 33.7% (P = .66) (ProCESS Investigators, et al. N Engl J Med. 2014;370[18]:1683-93).

ARISE: ARISE was a 1,600-patient randomized trial comparing the impact of EGDT vs usual care on 90-day all-cause mortality in patients with early septic shock at 51 hospitals in New Zealand and Australia. There was no significant difference in the primary study end point with 90-day mortality rates of 18.6% and 18.8% (RR: 0.98, 95% CI: 0.80-1.21, P = .90). There were also no significant differences in 28-day or in-hospital mortality, duration of organ support, or length of hospital stay (ARISE Investigators, et al. N Engl J Med. 2014;371[16]:1496-506).

In summary, all three “triad” trials found no improvement with EGDT over usual care (Rowan, et al. N Engl J Med. 2017;376[23]:2223-34) calling into question the recommended methods of universally protocolized approaches to fluid and pressor resuscitation. Probable reasons for why structured EGDT was ineffective at improving outcomes over usual care in the “triad” trials was that (a) liberal fluid volume administration was the “usual care” in most enrolled patients and (b) that macrocirculatory hemodynamics, such as BP, and static intravascular pressures such as CVP and pulmonary arterial wedge pressure are poor correlates and predictors of effective circulatory volumes and the presence of fluid responsiveness.

Counterintuitively, in situations of central hypovolemia, peripheral sympathetic activity remains high in many patients while stroke volume decreases. This provides insight into why some patients appear not to benefit from fluid administration as peripheral arterial pressure may be maintained despite low central filling pressure (Convertino VA, et al. Auton Neurosci. 2004;111[2]:127-34). Many patients with sepsis and septic shock initially present in an undifferentiated state and empiric treatment decisions regarding fluid and pressor treatments are then misaligned to functional physiological status.

Novel methods and approaches are needed to differentiate these patients and provide appropriate, physiologically guided fluid resuscitation. Dynamic measurement of stroke volume (SV) after a passive leg raise (PLR) or a small IV fluid challenge is an emerging method for determining fluid responsiveness. Evidence suggests that the use of SV-guided resuscitation can reduce net fluid balance, ICU length of stay, risk of mechanical ventilation, time on vasopressors, and risk of renal replacement therapy.(Latham HE, et al. J Crit Care. 2017;42:42-6).

In addition to the lack of efficacy from administering fluid to nonfluid responsive patients, there remains a risk of over-resuscitation from excessive fluid administration. Excessive fluid administration causes hypervolemia and is associated with a variety of negative patient outcomes including tissue edema, organ dysfunction, increased ICU length of stay, prolonged ventilator dependence, and higher mortality rates (Tigabu BM, et al. J Crit Care. 2018;48:153-9). Further, unnecessary initial fluid administration necessitates a “de-resuscitative” phase that can prolong hospital stay and is associated with amplification of sepsis-associated organ failures. Specifically, a 2017 analysis of hospital discharge data found that large volume fluid resuscitation in sepsis patients during the first 24 hours of care was associated with higher rates of hospital mortality than was predicted for patients’ disease severity (Mansoori JN, et al. Crit Care. 2020;24[1]:25).
 

The FRESH trial

The Fluid Response Evaluation in Sepsis Hypotension and Shock (FRESH) trial was a prospective, randomized clinical trial in adults with septic shock comparing PLR-guided SV responsiveness (intervention) as a guide for fluid management with usual care. Patients presented to the ER with sepsis-associated hypotension and anticipated ICU admission. In the intervention arm, patients were assessed for fluid responsiveness (FR) before any clinically driven fluid bolus or increase in vasopressors. If a patient’s stroke volume increased by ≥10% in response to a PLR, they were considered fluid responsive and fluid was recommended as the first therapy. If a patient’s stroke volume increased by <10% then the patient was considered not to be FR and vasopressors were recommended as first-line therapy. The control arm received usual care. The primary end point was the difference in positive fluid balance at the first of either 72 hours or ICU discharge. Patients had received ~2.3 L of crystalloid fluid prior to randomization (~3.5 h from initial presentation), in keeping with 30 mL/kg recommendations. Patients treated with the PLR-guided fluid and pressor protocol had a significant lower net fluid balance (1.37 L (95% CI: 2.53-0.21, P = .021) at 72 hours or ICU discharge. In addition, the intervention group experienced significantly less frequent requirement for renal replacement therapy with a difference of 12.4% (95% CI: 27%-1%, P = .042) as well as a decreased requirement for ventilator use with a difference of 16.42% (95% CI: 33%-0%, P = .044) (Douglas IS, et al. Chest. 2020;158[4]:1431-45).

FRESH demonstrated that PLR-guided FR drove lower fluid balance in patients with septic shock who present to the ER with sepsis and creates a paradigm for future management of fluid and pressor resuscitation beyond the initial 30 mL/kg bolus. Functional evaluation for lack of FR adequately identifies a group of patients with sepsis-associated hypotension who are unlikely to benefit from additional IV fluids to establish hemodynamically stability. It facilitated physiologically informed treatment decisions for the individual patient at a specific moment in their course of treatment as opposed to relying on static measurements and goals that may ultimately not be indicative of fluid responsiveness and circulatory effectiveness. This could reduce the likelihood of fluid overload and associated organ failure and, thus, improve patient outcomes.

Microcirculatory function is significantly impacted by sepsis with a decline in capillary density and inappropriate vasodilation/constriction resulting in insufficient tissue and organ perfusion and increased oxidative stress. Such dysfunction has been found to be associated with worsened patient outcomes, including mortality. However, microcirculatory function does not correlate well with traditionally used macrohemodynamic assessments and treating to improve macrohemodynamic values does not ensure that microcirculation will improve (Charlton M, et al. J Intensive Care Soc. 2017;18(3):221-7).

Ongoing studies are exploring if dynamic fluid-guided resuscitation has the potential to improve survival in sepsis by providing insight into whether the administration of fluid will impact the microcirculation and subsequent organ perfusion of the patient.

Future directions include expanding the dynamic treatment algorithm into other settings, such as rapid response calls, or other patient populations, including those initially presenting with undifferentiated hypotension. While FRESH was not sufficiently powered to detect differences in mortality, there are currently multiple large studies being conducted aimed at determining the impact of a restricted fluid and early vasopressor strategy as compared with a large initial IV fluid bolus on mortality. The results of these studies could be used to determine if the results of FRESH will translate into patient survival outcomes.