New systemic lupus erythematosus guidelines from the European League Against Rheumatism go far beyond the group’s previous effort in 2008, with much broader and more detailed advice.

enot-poloskun/iStock/Getty Images Plus

The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.

The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).

A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.

The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.

Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.

For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.


Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.

aotto@mdedge.com

SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089

New systemic lupus erythematosus guidelines from the European League Against Rheumatism go far beyond the group’s previous effort in 2008, with much broader and more detailed advice.

enot-poloskun/iStock/Getty Images Plus

The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.

The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).

A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.

The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.

Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.

For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.


Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.

aotto@mdedge.com

SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089

New systemic lupus erythematosus guidelines from the European League Against Rheumatism go far beyond the group’s previous effort in 2008, with much broader and more detailed advice.

enot-poloskun/iStock/Getty Images Plus

The goal was “to update the EULAR recommendations for the management of systemic lupus erythematosus [SLE], based on literature review and expert consensus,” said authors led by Antonis Fanouriakis, MD, PhD, of the rheumatology and clinical immunology unit at Attikon University Hospital, Athens.

The team accomplished their aim in 33 recommendations – about twice as many as in 2008 – covering goals of therapy, treatment, specific manifestations, and comorbidities (Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089).

A lot has changed in the past 11 years, and the new guidelines reflect that. Biologics, for instance, were barely mentioned in 2008, except as a topic for future research. The new document makes a strong recommendation for add-on belimumab (Benlysta) to be considered in persistently active or flaring extrarenal disease, and rituximab (Rituxan) for organ-threatening, refractory disease.

The group now also makes a strong recommendation for hydroxychloroquine (Plaquenil) for all lupus patients, barring contraindications, at a dose not exceeding 5 mg per kg real body weight, with ophthalmologic screening performed at baseline, after 5 years, and yearly thereafter. It also calls for routine antiphospholipid antibody testing.

Calcineurin inhibitors weren’t mentioned at all in 2008, but they show up in the new document with a moderate recommendation as first-line topical options for skin disease, along with glucocorticoids. The authors also made a moderate recommendation for diagnostic kidney biopsy, calling it “essential” to catch renal involvement early; EULAR was less certain in 2008. Also new in 2019, and barely mentioned in 2008, there’s an entire section on hematologic manifestations, as well as advice on thalidomide for cutaneous disease.

For hematologic disease, the group makes a weak recommendation for pulsed intravenous methylprednisolone and/or intravenous immunoglobulin, with mycophenolate, azathioprine, or cyclosporine for maintenance. Cyclophosphamide, along with rituximab, are options for severe hematologic cases.


Cardiovascular disease, like biologics, was mentioned mostly in 2008 as a topic for future research; the new guidelines contain an entire section on the issue. There’s a strong recommendation for regular assessment of traditional and disease-related risk factors, including persistently active disease; increased disease duration; medium or high titers of antiphospholipid antibodies; renal involvement; and chronic glucocorticoid use. High-risk people, the document notes, “may be candidates for preventative strategies as in the general population,” including low-dose aspirin and statins.

aotto@mdedge.com

SOURCE: Fanouriakis A et al. Ann Rheum Dis. 2019 Mar 29. doi: 10.1136/annrheumdis-2019-215089

For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.

The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.

This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.

“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.

These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.

The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.

Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.

The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.

Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.

“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.

Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.

SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.

For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.

The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.

This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.

“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.

These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.

The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.

Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.

The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.

Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.

“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.

Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.

SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.

For patients with centrally located lung cancers in a multicenter phase 1/2 trial, a specific five-fraction radiotherapy schedule was well tolerated and linked to fairly low rates of treatment-related toxicity, investigators say.

The 12-Gy/fraction schedule of stereotactic body radiotherapy (SBRT) had a 7.2% rate of dose-limiting toxicities and a high tumor-control rate in the NRG Oncology/RTOG 0813 trial, which enrolled 120 patients with medically inoperable stage T1/2 N0M0 non–small cell lung cancers at 43 centers in the United States and Canada.

This is an important study that has implications for clinical practice, according to the investigators, led by Andrea Bezjak, MD, of Princess Margaret Cancer Centre in Toronto.

“The ability to treat patients with centrally located node-negative tumors in multiple institutions across the United States and Canada while maintaining plan qualities and achieving good patient outcomes and relatively modest rates of toxicity is an important achievement,” Dr. Bezjak and coinvestigators said in the Journal of Clinical Oncology.

These patients are frequently at increased risk from surgery, because of advanced age and the comorbidities that come with it, they added.

The 12-Gy/fraction dose level was the highest of nine dose levels included in the study protocol. Doses were delivered in five fractions over the course of 1.5-2 weeks. Investigators sought to determine the maximum tolerated dose of SRBT, defined as the level at which the probability of dose-limiting toxicities (grade 3 or greater) within the first year was as close to 20% as possible, without going over.

Thus, the 7.2% rate of dose-limiting toxicities at this highest-allowed dose level was “well below” that protocol-specified threshold, investigators said, commenting on results of the study.

The rate of local control at 2 years was 89.4% for the 12-Gy/fraction dose level. The 2-year overall survival was 70%, which compared favorably to what has been seen previously with use of SBRT in similar patients with peripheral tumors, according to Dr. Bezjak and colleagues.

Most deaths in the study were attributable to causes other than lung cancer, according to investigators, who noted that all accrued patients were deemed medically inoperable by an experienced thoracic surgeon.

“Thus, this study provides robust data about the safety and efficacy of a five-fraction SBRT schedule that is well tolerated and associated with relatively low rates of serious treatment-related toxicity,” they concluded.

Dr. Bezjak reported disclosures related to AstraZeneca and Abbvie. Coauthors provided disclosures related to Varian Medical Systems, Elekta, Accuray, Seattle Genetics, Celgene, Exelixis, Gilead Sciences, Illumina, Ions Pharmaceuticals, and EMD Serono, among others.

SOURCE: Bezjak A et al. J Clin Oncol. 2019 Apr 3. doi: 10.1200/JCO.18.00622.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 59-year-old man with cirrhosis secondary to nonalcoholic steatohepatitis was admitted to the intensive care unit (ICU) for management of hepatorenal syndrome and work-up for liver transplantation. On admission, his platelet count was 90 × 109/L (normal 150-400 × 109/L), and he was started on thromboprophylaxis with unfractionated heparin (UFH) 5,000 units subcutaneously twice daily. His platelet count began to fall two days after admission. He did have a history of prior heparin exposure associated with his hemodialysis sessions in the past 30 days. During this period, he also had an episode of fever, and antibiotics were initiated for a presumed line infection. He also required periodic vasopressor support for hypotension. His platelet count reached 14 × 109/L by the end of two weeks. He did not have any symptoms of thrombosis, skin necrosis, or reaction to heparin exposure.

Thrombocytopenia is common, especially during critical illness, occurring in up to 50% of patients.¹ In this population, thrombocytopenia is often due to sepsis, hemorrhage, liver dysfunction, and drug reactions.^1,2 Heparin-induced thrombocytopenia (HIT) is an acquired thrombotic drug reaction resulting from platelet activation secondary to antibodies formed against the heparin-modified platelet factor 4 (PF4) complexes.³ This leads to platelet aggregation and dysregulation of the coagulation cascade, which can result in arterial or venous thromboembolic events in up to 50% of patients.³ Mortality associated with HIT can be as high as 30% in this critically ill population.³ Diagnosis of HIT can be made initially through the enzyme-linked immunosorbent assay (ELISA). Management of HIT involves immediate cessation of heparin and initiation of therapeutic anticoagulation with nonheparin agents in order to prevent or treat the thrombotic events.^4,5

The true incidence of HIT remains low, occurring in 0.2% to 5% of patients exposed to heparin and less than 1% in the ICU population.^2,3,6,7 However, given the high incidence of thrombocytopenia in the ICU, the diagnosis of HIT is often considered, resulting in over-testing in this population. Studies suggest that more than 200 ELISAs are requested per year at many hospitals.^8,9 This can lead to significant clinical and economic consequences.

Thrombocytopenia is common in hospitalized patients while heparin is frequently used for thromboprophylaxis or therapeutic anticoagulation. As a result, a diagnosis of HIT is often considered.¹ The high stakes of the inpatient environment, coupled with the increased frequency of thrombocytopenia and heparin exposure, has led to increased use of HIT testing in this population.¹⁰

The most widely available diagnostic test for HIT is the ELISA which detects anti-PF4-heparin antibodies but also nonpathogenic antibodies.¹¹ As a result, the ELISA has a sensitivity close to 100%, allowing physicians to rule out HIT if the test is negative, as indicated by an optical density (OD) of less than 0.4.⁷ Confirmatory testing with the functional serotonin release assay (SRA) is the reference standard as it confers both a high sensitivity and specificity for HIT.¹¹ Due to technical aspects, SRA, unlike the ELISA, is not available in every center and is often outsourced to external labs. Turn-around time for external SRA testing can vary from days to weeks versus hours for the ELISA. The cost for SRA is approximately $120 (USD) per test compared to $30 (USD) per ELISA. Therefore, the ELISA is the recommended initial test due to its quick turn-around time and lower costs.^12,13 For these reasons, the SRA test should not be used initially, but rather to confirm the diagnosis of HIT in patients with a positive ELISA.

The “4T’s” scoring system is a clinical scoring system that estimates the pretest probability of HIT using clinical and basic laboratory parameters (Table).¹⁴ The 4T’s score provides a pretest probability for HIT using four parameters: platelet count, timing of platelet fall, presence of thrombotic events, and the likelihood of another cause of thrombocytopenia. Based on these parameters, the pretest probability for HIT can be divided into three categories: low (4T’s score of ≤3), intermediate (score 4-5), or high (score 6-8).^14-16

Validation of the 4T’s score has shown that a low probability score carries a negative predictive value of 99% in a patient population with varying HIT prevalence rates.¹⁴ Therefore, having a low score is sufficient to rule out HIT without the need for further laboratory testing.^14-16 Although the HIT ELISA confers high sensitivity, due to its detection of nonpathogenic antibodies, its specificity can range from 74% to 84%.¹⁵ Therefore, in the setting of a low 4T’s score, HIT testing is not only unnecessary, it can be harmful due to the risk of treating a false positive result. For instance, assuming an average HIT prevalence of 1% and a false positive rate of 16% (specificity 84%), 1/17 (5.6%) patients with a positive ELISA will have HIT if testing is pursued in an indiscriminate manner. The American Society of Hematology Choosing Wisely^® Campaign has highlighted this concern by advising physicians that they should “not test or treat for suspected HIT in patients with a low pretest probability of HIT.”¹⁷

False positive results on HIT tests are not a trivial concern. The most recognizable adverse event associated with HIT treatment is an elevated risk of bleeding while receiving nonheparin agents. Availability of nonheparin anticoagulants vary by center; however, the most commonly used agents include argatroban, danaparoid, bivalirudin, and off-label fondaparinux.⁴ Due to its short half-life and hepatic clearance, argatroban is commonly used for cases of confirmed or suspected HIT. A retrospective study assessing the bleeding risk of critically ill patients on argatroban therapy suggests a major bleeding risk of 10% within two days of argatroban initiation.¹⁸ In addition, factors such as the presence of elevated bilirubin, major surgery, weight >90 kg, and platelet count <70 × 109/L were found to be associated with increased risk for major bleeding.¹⁸ These identified risk factors are very common in the inpatient setting. As a result, monitoring and titration of argatroban can be challenging.

Over-diagnosis and over-treatment can also lead to significant costs to the healthcare system. A retrospective study assessing the use of HIT testing found that out of 218 HIT ELISA’s sent over a one-year period at a single institution, 161 (74%) were sent inappropriately (ie, in patients with a low pretest probability), with only one resulting in confirmed HIT by SRA. This incurred an additional cost of $33,000 (USD) for testing alone.⁸ A retrospective study of 85 patients assessed the costs of treating patients with a false positive HIT assay. They found that the average duration of treatment with a nonheparin agent was three days and the total cost per patient was $982 (USD).¹⁹ Treatment with a nonheparin agent such as argatroban costs more than $700 (USD) per day while the continuation of unfractionated heparin for prophylaxis costs less than $10 (USD) per day.²⁰Lastly, a diagnosis of HIT can also result in late consequences due to heparin re-exposure. Clinicians may be wary of exposing patients to heparin in situations where heparin may be the most appropriate agent such as cardiovascular surgery, percutaneous interventions, routine thromboprophylaxis, or therapeutic anticoagulation. In these situations when heparin is the agent of choice, determining safety for re-exposure requires further antibody testing which may delay procedures or result in the use of alternative agents with their associated risks and cost implications.⁴

Laboratory testing for HIT is appropriate when the pretest probability for HIT is intermediate or high based on the 4T’s score.^14-16 Studies assessing the application of the 4T’s score have shown that a moderate or high pretest probability carries a probability of having true HIT in 14% and 64% of the cases respectively.¹⁴ However, due to the subjective nature of the 4T’s score components, it is important to recognize that in nonexpert hands, the 4T’s scoring system can suffer from a lack of interrater reliability.¹⁶

As discussed above, a negative ELISA (OD < 0.4) helps to rule out HIT and allow heparin to be safely reintroduced without any further testing. If ELISA is positive (OD ≥ 0.4) confirmation testing with SRA should be performed.⁵ However, studies suggest that the magnitude of the OD is associated with increased likelihood for true HIT, with an OD of greater than 2.00 associated with a positive SRA approximately 90% of the time.²¹ This suggests that if OD values are strongly positive (≥2.00), SRA can be deferred.⁵

Due to the SRA limited availability, confirmatory testing is not always possible or in some situations, SRA results may be negative despite a positive OD. In both these cases, discussion with the Hematology service is recommended.

When presented with a case of thrombocytopenia, it is important for clinicians to consider a broad approach in their differential diagnosis. Hospitalists should investigate common etiologies, consider the coagulation parameters, liver enzymes, nutritional status, peripheral blood smear, and a detailed history and physical exam to identify other common potential cause such as sepsis.

The 4T’s score should be applied in patients who have had recent heparin exposure. A score of ≤3 indicates a low pretest probability; therefore, HIT is unlikely and further testing is not needed. A score of ≥4 indicates an intermediate or high pretest probability and should prompt clinicians to consider further HIT testing with ELISA. In these situations, heparin should be held, and nonheparin agents should be initiated to prevent thromboembolic complications. In their study of ICU patients, Pierce et al. found that 17% of patients did not have a concurrent cessation of heparin and initiation of alternative agents despite a high clinical suspicion for HIT.¹ Lastly, if hospitalists have concerns regarding HIT testing or management, expert consultation with the Hematology service is recommended.

• Consider a broad differential diagnosis when presented with a hospitalized patient with new thrombocytopenia given the low incidence of HIT (<5%).
• Apply the 4T’s score in those who have thrombocytopenia and recent heparin exposure. A low scores 4T’s score (≤3) predicts a low pretest probability and further testing is not required.
• Patients with moderate or high 4T’s score (≥4) should have the ELISA test. During this time, heparin should be discontinued and nonheparin agents initiated while waiting for test results.
• Confirmatory testing with SRA should be performed for all positive ELISAs; however, they can be deferred in patients with strongly positive OD (≥2.00) on ELISA.

In the opening clinical scenario, the 4T’s score would have been 2 (1 point for the platelet count, 1 point for the platelet count fall after 10 days, 0 points for thrombosis, and 0 points for an alternative cause of thrombocytopenia), indicating a low pretest probability. Further HIT testing should be deferred as the likelihood for HIT is low. In this case, the more likely etiology for his thrombocytopenia would be sepsis. Therefore, heparin can be safely reinitiated once the platelet count recovers. This case helps to illustrate the importance of keeping a broad differential in cases of thrombocytopenia in the hospitalized patient while concurrently applying the 4T’s score to determine appropriateness for further HIT testing. Ultimately by choosing wisely, we can help reduce the cost and safety implications of a falsely positive HIT diagnosis.

What do you do?

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.

Disclosures

The authors report no conflict of interest.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 59-year-old man with cirrhosis secondary to nonalcoholic steatohepatitis was admitted to the intensive care unit (ICU) for management of hepatorenal syndrome and work-up for liver transplantation. On admission, his platelet count was 90 × 109/L (normal 150-400 × 109/L), and he was started on thromboprophylaxis with unfractionated heparin (UFH) 5,000 units subcutaneously twice daily. His platelet count began to fall two days after admission. He did have a history of prior heparin exposure associated with his hemodialysis sessions in the past 30 days. During this period, he also had an episode of fever, and antibiotics were initiated for a presumed line infection. He also required periodic vasopressor support for hypotension. His platelet count reached 14 × 109/L by the end of two weeks. He did not have any symptoms of thrombosis, skin necrosis, or reaction to heparin exposure.

Thrombocytopenia is common, especially during critical illness, occurring in up to 50% of patients.¹ In this population, thrombocytopenia is often due to sepsis, hemorrhage, liver dysfunction, and drug reactions.^1,2 Heparin-induced thrombocytopenia (HIT) is an acquired thrombotic drug reaction resulting from platelet activation secondary to antibodies formed against the heparin-modified platelet factor 4 (PF4) complexes.³ This leads to platelet aggregation and dysregulation of the coagulation cascade, which can result in arterial or venous thromboembolic events in up to 50% of patients.³ Mortality associated with HIT can be as high as 30% in this critically ill population.³ Diagnosis of HIT can be made initially through the enzyme-linked immunosorbent assay (ELISA). Management of HIT involves immediate cessation of heparin and initiation of therapeutic anticoagulation with nonheparin agents in order to prevent or treat the thrombotic events.^4,5

The true incidence of HIT remains low, occurring in 0.2% to 5% of patients exposed to heparin and less than 1% in the ICU population.^2,3,6,7 However, given the high incidence of thrombocytopenia in the ICU, the diagnosis of HIT is often considered, resulting in over-testing in this population. Studies suggest that more than 200 ELISAs are requested per year at many hospitals.^8,9 This can lead to significant clinical and economic consequences.

Thrombocytopenia is common in hospitalized patients while heparin is frequently used for thromboprophylaxis or therapeutic anticoagulation. As a result, a diagnosis of HIT is often considered.¹ The high stakes of the inpatient environment, coupled with the increased frequency of thrombocytopenia and heparin exposure, has led to increased use of HIT testing in this population.¹⁰

The most widely available diagnostic test for HIT is the ELISA which detects anti-PF4-heparin antibodies but also nonpathogenic antibodies.¹¹ As a result, the ELISA has a sensitivity close to 100%, allowing physicians to rule out HIT if the test is negative, as indicated by an optical density (OD) of less than 0.4.⁷ Confirmatory testing with the functional serotonin release assay (SRA) is the reference standard as it confers both a high sensitivity and specificity for HIT.¹¹ Due to technical aspects, SRA, unlike the ELISA, is not available in every center and is often outsourced to external labs. Turn-around time for external SRA testing can vary from days to weeks versus hours for the ELISA. The cost for SRA is approximately $120 (USD) per test compared to $30 (USD) per ELISA. Therefore, the ELISA is the recommended initial test due to its quick turn-around time and lower costs.^12,13 For these reasons, the SRA test should not be used initially, but rather to confirm the diagnosis of HIT in patients with a positive ELISA.

The “4T’s” scoring system is a clinical scoring system that estimates the pretest probability of HIT using clinical and basic laboratory parameters (Table).¹⁴ The 4T’s score provides a pretest probability for HIT using four parameters: platelet count, timing of platelet fall, presence of thrombotic events, and the likelihood of another cause of thrombocytopenia. Based on these parameters, the pretest probability for HIT can be divided into three categories: low (4T’s score of ≤3), intermediate (score 4-5), or high (score 6-8).^14-16

Validation of the 4T’s score has shown that a low probability score carries a negative predictive value of 99% in a patient population with varying HIT prevalence rates.¹⁴ Therefore, having a low score is sufficient to rule out HIT without the need for further laboratory testing.^14-16 Although the HIT ELISA confers high sensitivity, due to its detection of nonpathogenic antibodies, its specificity can range from 74% to 84%.¹⁵ Therefore, in the setting of a low 4T’s score, HIT testing is not only unnecessary, it can be harmful due to the risk of treating a false positive result. For instance, assuming an average HIT prevalence of 1% and a false positive rate of 16% (specificity 84%), 1/17 (5.6%) patients with a positive ELISA will have HIT if testing is pursued in an indiscriminate manner. The American Society of Hematology Choosing Wisely^® Campaign has highlighted this concern by advising physicians that they should “not test or treat for suspected HIT in patients with a low pretest probability of HIT.”¹⁷

False positive results on HIT tests are not a trivial concern. The most recognizable adverse event associated with HIT treatment is an elevated risk of bleeding while receiving nonheparin agents. Availability of nonheparin anticoagulants vary by center; however, the most commonly used agents include argatroban, danaparoid, bivalirudin, and off-label fondaparinux.⁴ Due to its short half-life and hepatic clearance, argatroban is commonly used for cases of confirmed or suspected HIT. A retrospective study assessing the bleeding risk of critically ill patients on argatroban therapy suggests a major bleeding risk of 10% within two days of argatroban initiation.¹⁸ In addition, factors such as the presence of elevated bilirubin, major surgery, weight >90 kg, and platelet count <70 × 109/L were found to be associated with increased risk for major bleeding.¹⁸ These identified risk factors are very common in the inpatient setting. As a result, monitoring and titration of argatroban can be challenging.

Over-diagnosis and over-treatment can also lead to significant costs to the healthcare system. A retrospective study assessing the use of HIT testing found that out of 218 HIT ELISA’s sent over a one-year period at a single institution, 161 (74%) were sent inappropriately (ie, in patients with a low pretest probability), with only one resulting in confirmed HIT by SRA. This incurred an additional cost of $33,000 (USD) for testing alone.⁸ A retrospective study of 85 patients assessed the costs of treating patients with a false positive HIT assay. They found that the average duration of treatment with a nonheparin agent was three days and the total cost per patient was $982 (USD).¹⁹ Treatment with a nonheparin agent such as argatroban costs more than $700 (USD) per day while the continuation of unfractionated heparin for prophylaxis costs less than $10 (USD) per day.²⁰Lastly, a diagnosis of HIT can also result in late consequences due to heparin re-exposure. Clinicians may be wary of exposing patients to heparin in situations where heparin may be the most appropriate agent such as cardiovascular surgery, percutaneous interventions, routine thromboprophylaxis, or therapeutic anticoagulation. In these situations when heparin is the agent of choice, determining safety for re-exposure requires further antibody testing which may delay procedures or result in the use of alternative agents with their associated risks and cost implications.⁴

Laboratory testing for HIT is appropriate when the pretest probability for HIT is intermediate or high based on the 4T’s score.^14-16 Studies assessing the application of the 4T’s score have shown that a moderate or high pretest probability carries a probability of having true HIT in 14% and 64% of the cases respectively.¹⁴ However, due to the subjective nature of the 4T’s score components, it is important to recognize that in nonexpert hands, the 4T’s scoring system can suffer from a lack of interrater reliability.¹⁶

As discussed above, a negative ELISA (OD < 0.4) helps to rule out HIT and allow heparin to be safely reintroduced without any further testing. If ELISA is positive (OD ≥ 0.4) confirmation testing with SRA should be performed.⁵ However, studies suggest that the magnitude of the OD is associated with increased likelihood for true HIT, with an OD of greater than 2.00 associated with a positive SRA approximately 90% of the time.²¹ This suggests that if OD values are strongly positive (≥2.00), SRA can be deferred.⁵

Due to the SRA limited availability, confirmatory testing is not always possible or in some situations, SRA results may be negative despite a positive OD. In both these cases, discussion with the Hematology service is recommended.

When presented with a case of thrombocytopenia, it is important for clinicians to consider a broad approach in their differential diagnosis. Hospitalists should investigate common etiologies, consider the coagulation parameters, liver enzymes, nutritional status, peripheral blood smear, and a detailed history and physical exam to identify other common potential cause such as sepsis.

The 4T’s score should be applied in patients who have had recent heparin exposure. A score of ≤3 indicates a low pretest probability; therefore, HIT is unlikely and further testing is not needed. A score of ≥4 indicates an intermediate or high pretest probability and should prompt clinicians to consider further HIT testing with ELISA. In these situations, heparin should be held, and nonheparin agents should be initiated to prevent thromboembolic complications. In their study of ICU patients, Pierce et al. found that 17% of patients did not have a concurrent cessation of heparin and initiation of alternative agents despite a high clinical suspicion for HIT.¹ Lastly, if hospitalists have concerns regarding HIT testing or management, expert consultation with the Hematology service is recommended.

• Consider a broad differential diagnosis when presented with a hospitalized patient with new thrombocytopenia given the low incidence of HIT (<5%).
• Apply the 4T’s score in those who have thrombocytopenia and recent heparin exposure. A low scores 4T’s score (≤3) predicts a low pretest probability and further testing is not required.
• Patients with moderate or high 4T’s score (≥4) should have the ELISA test. During this time, heparin should be discontinued and nonheparin agents initiated while waiting for test results.
• Confirmatory testing with SRA should be performed for all positive ELISAs; however, they can be deferred in patients with strongly positive OD (≥2.00) on ELISA.

In the opening clinical scenario, the 4T’s score would have been 2 (1 point for the platelet count, 1 point for the platelet count fall after 10 days, 0 points for thrombosis, and 0 points for an alternative cause of thrombocytopenia), indicating a low pretest probability. Further HIT testing should be deferred as the likelihood for HIT is low. In this case, the more likely etiology for his thrombocytopenia would be sepsis. Therefore, heparin can be safely reinitiated once the platelet count recovers. This case helps to illustrate the importance of keeping a broad differential in cases of thrombocytopenia in the hospitalized patient while concurrently applying the 4T’s score to determine appropriateness for further HIT testing. Ultimately by choosing wisely, we can help reduce the cost and safety implications of a falsely positive HIT diagnosis.

What do you do?

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.

Disclosures

The authors report no conflict of interest.

Inspired by the ABIM Foundation’s Choosing Wisely^® campaign, the “Things We Do for No Reason” series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion.

A 59-year-old man with cirrhosis secondary to nonalcoholic steatohepatitis was admitted to the intensive care unit (ICU) for management of hepatorenal syndrome and work-up for liver transplantation. On admission, his platelet count was 90 × 109/L (normal 150-400 × 109/L), and he was started on thromboprophylaxis with unfractionated heparin (UFH) 5,000 units subcutaneously twice daily. His platelet count began to fall two days after admission. He did have a history of prior heparin exposure associated with his hemodialysis sessions in the past 30 days. During this period, he also had an episode of fever, and antibiotics were initiated for a presumed line infection. He also required periodic vasopressor support for hypotension. His platelet count reached 14 × 109/L by the end of two weeks. He did not have any symptoms of thrombosis, skin necrosis, or reaction to heparin exposure.

Thrombocytopenia is common, especially during critical illness, occurring in up to 50% of patients.¹ In this population, thrombocytopenia is often due to sepsis, hemorrhage, liver dysfunction, and drug reactions.^1,2 Heparin-induced thrombocytopenia (HIT) is an acquired thrombotic drug reaction resulting from platelet activation secondary to antibodies formed against the heparin-modified platelet factor 4 (PF4) complexes.³ This leads to platelet aggregation and dysregulation of the coagulation cascade, which can result in arterial or venous thromboembolic events in up to 50% of patients.³ Mortality associated with HIT can be as high as 30% in this critically ill population.³ Diagnosis of HIT can be made initially through the enzyme-linked immunosorbent assay (ELISA). Management of HIT involves immediate cessation of heparin and initiation of therapeutic anticoagulation with nonheparin agents in order to prevent or treat the thrombotic events.^4,5

The true incidence of HIT remains low, occurring in 0.2% to 5% of patients exposed to heparin and less than 1% in the ICU population.^2,3,6,7 However, given the high incidence of thrombocytopenia in the ICU, the diagnosis of HIT is often considered, resulting in over-testing in this population. Studies suggest that more than 200 ELISAs are requested per year at many hospitals.^8,9 This can lead to significant clinical and economic consequences.

Thrombocytopenia is common in hospitalized patients while heparin is frequently used for thromboprophylaxis or therapeutic anticoagulation. As a result, a diagnosis of HIT is often considered.¹ The high stakes of the inpatient environment, coupled with the increased frequency of thrombocytopenia and heparin exposure, has led to increased use of HIT testing in this population.¹⁰

The most widely available diagnostic test for HIT is the ELISA which detects anti-PF4-heparin antibodies but also nonpathogenic antibodies.¹¹ As a result, the ELISA has a sensitivity close to 100%, allowing physicians to rule out HIT if the test is negative, as indicated by an optical density (OD) of less than 0.4.⁷ Confirmatory testing with the functional serotonin release assay (SRA) is the reference standard as it confers both a high sensitivity and specificity for HIT.¹¹ Due to technical aspects, SRA, unlike the ELISA, is not available in every center and is often outsourced to external labs. Turn-around time for external SRA testing can vary from days to weeks versus hours for the ELISA. The cost for SRA is approximately $120 (USD) per test compared to $30 (USD) per ELISA. Therefore, the ELISA is the recommended initial test due to its quick turn-around time and lower costs.^12,13 For these reasons, the SRA test should not be used initially, but rather to confirm the diagnosis of HIT in patients with a positive ELISA.

The “4T’s” scoring system is a clinical scoring system that estimates the pretest probability of HIT using clinical and basic laboratory parameters (Table).¹⁴ The 4T’s score provides a pretest probability for HIT using four parameters: platelet count, timing of platelet fall, presence of thrombotic events, and the likelihood of another cause of thrombocytopenia. Based on these parameters, the pretest probability for HIT can be divided into three categories: low (4T’s score of ≤3), intermediate (score 4-5), or high (score 6-8).^14-16

Validation of the 4T’s score has shown that a low probability score carries a negative predictive value of 99% in a patient population with varying HIT prevalence rates.¹⁴ Therefore, having a low score is sufficient to rule out HIT without the need for further laboratory testing.^14-16 Although the HIT ELISA confers high sensitivity, due to its detection of nonpathogenic antibodies, its specificity can range from 74% to 84%.¹⁵ Therefore, in the setting of a low 4T’s score, HIT testing is not only unnecessary, it can be harmful due to the risk of treating a false positive result. For instance, assuming an average HIT prevalence of 1% and a false positive rate of 16% (specificity 84%), 1/17 (5.6%) patients with a positive ELISA will have HIT if testing is pursued in an indiscriminate manner. The American Society of Hematology Choosing Wisely^® Campaign has highlighted this concern by advising physicians that they should “not test or treat for suspected HIT in patients with a low pretest probability of HIT.”¹⁷

False positive results on HIT tests are not a trivial concern. The most recognizable adverse event associated with HIT treatment is an elevated risk of bleeding while receiving nonheparin agents. Availability of nonheparin anticoagulants vary by center; however, the most commonly used agents include argatroban, danaparoid, bivalirudin, and off-label fondaparinux.⁴ Due to its short half-life and hepatic clearance, argatroban is commonly used for cases of confirmed or suspected HIT. A retrospective study assessing the bleeding risk of critically ill patients on argatroban therapy suggests a major bleeding risk of 10% within two days of argatroban initiation.¹⁸ In addition, factors such as the presence of elevated bilirubin, major surgery, weight >90 kg, and platelet count <70 × 109/L were found to be associated with increased risk for major bleeding.¹⁸ These identified risk factors are very common in the inpatient setting. As a result, monitoring and titration of argatroban can be challenging.

Over-diagnosis and over-treatment can also lead to significant costs to the healthcare system. A retrospective study assessing the use of HIT testing found that out of 218 HIT ELISA’s sent over a one-year period at a single institution, 161 (74%) were sent inappropriately (ie, in patients with a low pretest probability), with only one resulting in confirmed HIT by SRA. This incurred an additional cost of $33,000 (USD) for testing alone.⁸ A retrospective study of 85 patients assessed the costs of treating patients with a false positive HIT assay. They found that the average duration of treatment with a nonheparin agent was three days and the total cost per patient was $982 (USD).¹⁹ Treatment with a nonheparin agent such as argatroban costs more than $700 (USD) per day while the continuation of unfractionated heparin for prophylaxis costs less than $10 (USD) per day.²⁰Lastly, a diagnosis of HIT can also result in late consequences due to heparin re-exposure. Clinicians may be wary of exposing patients to heparin in situations where heparin may be the most appropriate agent such as cardiovascular surgery, percutaneous interventions, routine thromboprophylaxis, or therapeutic anticoagulation. In these situations when heparin is the agent of choice, determining safety for re-exposure requires further antibody testing which may delay procedures or result in the use of alternative agents with their associated risks and cost implications.⁴

Laboratory testing for HIT is appropriate when the pretest probability for HIT is intermediate or high based on the 4T’s score.^14-16 Studies assessing the application of the 4T’s score have shown that a moderate or high pretest probability carries a probability of having true HIT in 14% and 64% of the cases respectively.¹⁴ However, due to the subjective nature of the 4T’s score components, it is important to recognize that in nonexpert hands, the 4T’s scoring system can suffer from a lack of interrater reliability.¹⁶

As discussed above, a negative ELISA (OD < 0.4) helps to rule out HIT and allow heparin to be safely reintroduced without any further testing. If ELISA is positive (OD ≥ 0.4) confirmation testing with SRA should be performed.⁵ However, studies suggest that the magnitude of the OD is associated with increased likelihood for true HIT, with an OD of greater than 2.00 associated with a positive SRA approximately 90% of the time.²¹ This suggests that if OD values are strongly positive (≥2.00), SRA can be deferred.⁵

Due to the SRA limited availability, confirmatory testing is not always possible or in some situations, SRA results may be negative despite a positive OD. In both these cases, discussion with the Hematology service is recommended.

When presented with a case of thrombocytopenia, it is important for clinicians to consider a broad approach in their differential diagnosis. Hospitalists should investigate common etiologies, consider the coagulation parameters, liver enzymes, nutritional status, peripheral blood smear, and a detailed history and physical exam to identify other common potential cause such as sepsis.

The 4T’s score should be applied in patients who have had recent heparin exposure. A score of ≤3 indicates a low pretest probability; therefore, HIT is unlikely and further testing is not needed. A score of ≥4 indicates an intermediate or high pretest probability and should prompt clinicians to consider further HIT testing with ELISA. In these situations, heparin should be held, and nonheparin agents should be initiated to prevent thromboembolic complications. In their study of ICU patients, Pierce et al. found that 17% of patients did not have a concurrent cessation of heparin and initiation of alternative agents despite a high clinical suspicion for HIT.¹ Lastly, if hospitalists have concerns regarding HIT testing or management, expert consultation with the Hematology service is recommended.

• Consider a broad differential diagnosis when presented with a hospitalized patient with new thrombocytopenia given the low incidence of HIT (<5%).
• Apply the 4T’s score in those who have thrombocytopenia and recent heparin exposure. A low scores 4T’s score (≤3) predicts a low pretest probability and further testing is not required.
• Patients with moderate or high 4T’s score (≥4) should have the ELISA test. During this time, heparin should be discontinued and nonheparin agents initiated while waiting for test results.
• Confirmatory testing with SRA should be performed for all positive ELISAs; however, they can be deferred in patients with strongly positive OD (≥2.00) on ELISA.

In the opening clinical scenario, the 4T’s score would have been 2 (1 point for the platelet count, 1 point for the platelet count fall after 10 days, 0 points for thrombosis, and 0 points for an alternative cause of thrombocytopenia), indicating a low pretest probability. Further HIT testing should be deferred as the likelihood for HIT is low. In this case, the more likely etiology for his thrombocytopenia would be sepsis. Therefore, heparin can be safely reinitiated once the platelet count recovers. This case helps to illustrate the importance of keeping a broad differential in cases of thrombocytopenia in the hospitalized patient while concurrently applying the 4T’s score to determine appropriateness for further HIT testing. Ultimately by choosing wisely, we can help reduce the cost and safety implications of a falsely positive HIT diagnosis.

What do you do?

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason”? Let us know what you do in your practice and propose ideas for other “Things We Do for No Reason” topics. Please join in the conversation online at Twitter (#TWDFNR)/Facebook and don’t forget to “Like It” on Facebook or retweet it on Twitter.

Disclosures

The authors report no conflict of interest.

Occupational and Environmental Health

Black lung disease in the 21st century

Inhalation and deposition of coal dust particles cause a range of lung injury from coal workers’ pneumoconiosis (CWP) to dust-related diffuse fibrosis to COPD. Despite workplace standards and improved environmental controls to limit dust exposure within coal mines, incidence of “black lung disease” in the United States has increased since the turn of the century (Antao VC, et al. Occup Environ Med. 2005;62[10]:670). Coal miners working in the Appalachian Mountains have been particularly vulnerable to developing rapidly progressive and severe pneumoconiosis. In 2018, three black lung clinics in central Appalachia uncovered the largest cluster of progressive massive fibrosis (PMF) ever reported (Blackley DJ, et al. JAMA. 2018;319[5]:500). An investigation by National Public Radio (NPR) and the Public Broadcasting Service (PBS) program Frontline identified more than 2,000 Appalachian coal miners suffering with PMF from 2011 to 2016, while only 99 cases of PMF were identified by the current federal monitoring program during the same period (https://goo.gl/ZJXp1W). Only about one-third of coal miners may participate in screening for black lung disease, and lack of participation could result from barriers such as fear of retaliation from employers (Siddons A. CQ-Roll Call, Inc. March 1, 2019; https://goo.gl/5mfVFvl). Ongoing research is studying factors leading to the resurgence in CWP. Increasing silica content in coal dust is a likely culprit that has escaped mine safety regulations. Given the rising incidence and the increasing morbidity and mortality of black lung disease, there is a need to educate and engage pulmonologists and others to improve surveillance and early recognition of the spectrum of coal-dust-related lung diseases to decrease morbidity and mortality among this vulnerable occupational group.

Drew Harris, MD
Amy Ahasic, MD, MPH, FCCP
Steering Committee Members

Palliative and End-of-Life Care

Importance of language and word choice when discussing cardiopulmonary resuscitation (CPR)

Words matter. Whether spoken or written, the words we choose when communicating with each other are fundamentally important, both by intention of the originator and the understanding of the audience, whether or not the meaning is imparted faithfully.

Respiratory Care

Low-tidal volume ventilation

Respir CMechanical ventilation in postoperative (post-op) patients is essential in care because it can determine the patient’s overall outcome, especially in post-op cardiovascular surgery patients. The risks of hemodynamic instability and consideration of total body organ function make choosing the correct strategy of mechanical ventilation vital (Ball, et al. Crit Care. 2016;22[4]:386). The current standard of practice for mechanically ventilated patients is to use low-tidal volume (LTV) ventilation, meaning administering 6-7 mL/kg of ideal body weight (Hoegl, et al. Anesthesiology. 2016;29[4]:94). The benefits of LTV ventilation include significantly decreased risk in lung injury, decreased risk of developing ARDS, and lessening of hemodynamic compromise (Hoegl, et al. 2016); (Stephens, et al. Crit Care Med. 2015;43:1477). Also, due to its high efficacy in terms of cost-effective care, such as shorter ICU stays and less number of days supported by mechanical ventilation, many hospitals have incorporated LTV strategy into the care of almost all post-op patients (Stephens, et al. 2015). However, no randomized controlled trials have been conducted in post-op cardiovascular patients undergoing mechanical ventilation to determine if LTV ventilation (6-7 mL/kg) has superior efficacy over higher levels of ventilation (8-10 mL/kg). This patient population tends to have normal lung function and, therefore, a LTV strategy could possibly be too conservative, whereas larger tidal volumes may be more comfortable and provide better ventilation considering the increased dead space in post-op cardiovascular patients. In order to address this gap in the literature, it is essential to determine if significant differences exist in patient mortality, ventilator days, hospital stay, and incidence of pulmonary complications for this population undergoing ventilation volumes of approximately 6 mL/kg or 8 mL/kg of ideal body weight.

Bethlehem Markos
Fellow-in-Training

Sleep Medicine

In case you missed it: Recent findings in obstructive sleep apnea

Lauren Tobias, MD
Steering Committee Member

Occupational and Environmental Health

Black lung disease in the 21st century

Inhalation and deposition of coal dust particles cause a range of lung injury from coal workers’ pneumoconiosis (CWP) to dust-related diffuse fibrosis to COPD. Despite workplace standards and improved environmental controls to limit dust exposure within coal mines, incidence of “black lung disease” in the United States has increased since the turn of the century (Antao VC, et al. Occup Environ Med. 2005;62[10]:670). Coal miners working in the Appalachian Mountains have been particularly vulnerable to developing rapidly progressive and severe pneumoconiosis. In 2018, three black lung clinics in central Appalachia uncovered the largest cluster of progressive massive fibrosis (PMF) ever reported (Blackley DJ, et al. JAMA. 2018;319[5]:500). An investigation by National Public Radio (NPR) and the Public Broadcasting Service (PBS) program Frontline identified more than 2,000 Appalachian coal miners suffering with PMF from 2011 to 2016, while only 99 cases of PMF were identified by the current federal monitoring program during the same period (https://goo.gl/ZJXp1W). Only about one-third of coal miners may participate in screening for black lung disease, and lack of participation could result from barriers such as fear of retaliation from employers (Siddons A. CQ-Roll Call, Inc. March 1, 2019; https://goo.gl/5mfVFvl). Ongoing research is studying factors leading to the resurgence in CWP. Increasing silica content in coal dust is a likely culprit that has escaped mine safety regulations. Given the rising incidence and the increasing morbidity and mortality of black lung disease, there is a need to educate and engage pulmonologists and others to improve surveillance and early recognition of the spectrum of coal-dust-related lung diseases to decrease morbidity and mortality among this vulnerable occupational group.

Drew Harris, MD
Amy Ahasic, MD, MPH, FCCP
Steering Committee Members

Palliative and End-of-Life Care

Importance of language and word choice when discussing cardiopulmonary resuscitation (CPR)

Words matter. Whether spoken or written, the words we choose when communicating with each other are fundamentally important, both by intention of the originator and the understanding of the audience, whether or not the meaning is imparted faithfully.

Respiratory Care

Low-tidal volume ventilation

Respir CMechanical ventilation in postoperative (post-op) patients is essential in care because it can determine the patient’s overall outcome, especially in post-op cardiovascular surgery patients. The risks of hemodynamic instability and consideration of total body organ function make choosing the correct strategy of mechanical ventilation vital (Ball, et al. Crit Care. 2016;22[4]:386). The current standard of practice for mechanically ventilated patients is to use low-tidal volume (LTV) ventilation, meaning administering 6-7 mL/kg of ideal body weight (Hoegl, et al. Anesthesiology. 2016;29[4]:94). The benefits of LTV ventilation include significantly decreased risk in lung injury, decreased risk of developing ARDS, and lessening of hemodynamic compromise (Hoegl, et al. 2016); (Stephens, et al. Crit Care Med. 2015;43:1477). Also, due to its high efficacy in terms of cost-effective care, such as shorter ICU stays and less number of days supported by mechanical ventilation, many hospitals have incorporated LTV strategy into the care of almost all post-op patients (Stephens, et al. 2015). However, no randomized controlled trials have been conducted in post-op cardiovascular patients undergoing mechanical ventilation to determine if LTV ventilation (6-7 mL/kg) has superior efficacy over higher levels of ventilation (8-10 mL/kg). This patient population tends to have normal lung function and, therefore, a LTV strategy could possibly be too conservative, whereas larger tidal volumes may be more comfortable and provide better ventilation considering the increased dead space in post-op cardiovascular patients. In order to address this gap in the literature, it is essential to determine if significant differences exist in patient mortality, ventilator days, hospital stay, and incidence of pulmonary complications for this population undergoing ventilation volumes of approximately 6 mL/kg or 8 mL/kg of ideal body weight.

Bethlehem Markos
Fellow-in-Training

Sleep Medicine

In case you missed it: Recent findings in obstructive sleep apnea

Lauren Tobias, MD
Steering Committee Member

Occupational and Environmental Health

Black lung disease in the 21st century

Inhalation and deposition of coal dust particles cause a range of lung injury from coal workers’ pneumoconiosis (CWP) to dust-related diffuse fibrosis to COPD. Despite workplace standards and improved environmental controls to limit dust exposure within coal mines, incidence of “black lung disease” in the United States has increased since the turn of the century (Antao VC, et al. Occup Environ Med. 2005;62[10]:670). Coal miners working in the Appalachian Mountains have been particularly vulnerable to developing rapidly progressive and severe pneumoconiosis. In 2018, three black lung clinics in central Appalachia uncovered the largest cluster of progressive massive fibrosis (PMF) ever reported (Blackley DJ, et al. JAMA. 2018;319[5]:500). An investigation by National Public Radio (NPR) and the Public Broadcasting Service (PBS) program Frontline identified more than 2,000 Appalachian coal miners suffering with PMF from 2011 to 2016, while only 99 cases of PMF were identified by the current federal monitoring program during the same period (https://goo.gl/ZJXp1W). Only about one-third of coal miners may participate in screening for black lung disease, and lack of participation could result from barriers such as fear of retaliation from employers (Siddons A. CQ-Roll Call, Inc. March 1, 2019; https://goo.gl/5mfVFvl). Ongoing research is studying factors leading to the resurgence in CWP. Increasing silica content in coal dust is a likely culprit that has escaped mine safety regulations. Given the rising incidence and the increasing morbidity and mortality of black lung disease, there is a need to educate and engage pulmonologists and others to improve surveillance and early recognition of the spectrum of coal-dust-related lung diseases to decrease morbidity and mortality among this vulnerable occupational group.

Drew Harris, MD
Amy Ahasic, MD, MPH, FCCP
Steering Committee Members

Palliative and End-of-Life Care

Importance of language and word choice when discussing cardiopulmonary resuscitation (CPR)

Words matter. Whether spoken or written, the words we choose when communicating with each other are fundamentally important, both by intention of the originator and the understanding of the audience, whether or not the meaning is imparted faithfully.

Respiratory Care

Low-tidal volume ventilation

Respir CMechanical ventilation in postoperative (post-op) patients is essential in care because it can determine the patient’s overall outcome, especially in post-op cardiovascular surgery patients. The risks of hemodynamic instability and consideration of total body organ function make choosing the correct strategy of mechanical ventilation vital (Ball, et al. Crit Care. 2016;22[4]:386). The current standard of practice for mechanically ventilated patients is to use low-tidal volume (LTV) ventilation, meaning administering 6-7 mL/kg of ideal body weight (Hoegl, et al. Anesthesiology. 2016;29[4]:94). The benefits of LTV ventilation include significantly decreased risk in lung injury, decreased risk of developing ARDS, and lessening of hemodynamic compromise (Hoegl, et al. 2016); (Stephens, et al. Crit Care Med. 2015;43:1477). Also, due to its high efficacy in terms of cost-effective care, such as shorter ICU stays and less number of days supported by mechanical ventilation, many hospitals have incorporated LTV strategy into the care of almost all post-op patients (Stephens, et al. 2015). However, no randomized controlled trials have been conducted in post-op cardiovascular patients undergoing mechanical ventilation to determine if LTV ventilation (6-7 mL/kg) has superior efficacy over higher levels of ventilation (8-10 mL/kg). This patient population tends to have normal lung function and, therefore, a LTV strategy could possibly be too conservative, whereas larger tidal volumes may be more comfortable and provide better ventilation considering the increased dead space in post-op cardiovascular patients. In order to address this gap in the literature, it is essential to determine if significant differences exist in patient mortality, ventilator days, hospital stay, and incidence of pulmonary complications for this population undergoing ventilation volumes of approximately 6 mL/kg or 8 mL/kg of ideal body weight.

Bethlehem Markos
Fellow-in-Training

Sleep Medicine

In case you missed it: Recent findings in obstructive sleep apnea

Lauren Tobias, MD
Steering Committee Member

Since the landmark ARMA trial, use of low tidal volume ventilation (LTVV) at 6 mL/kg predicted body weight (PBW) has become our gold standard for ventilator management in acute respiratory distress syndrome (ARDS) (Brower RG, et al. N Engl J Med. 2000;342[18]:1301). While other studies have suggested that patients without ARDS may also benefit from lower volumes, the recently published Protective Ventilation in Patients Without ARDS (PReVENT) trial found no benefit to using LTVV in non-ARDS patients (Simonis FD, et al. JAMA. 2018;320[18]:1872). Does this mean we let physicians set volumes at will? Is tidal volume (VT) even clinically relevant anymore in the non-ARDS population?

Prior to the PReVENT trial, our practice of LTVV for patients without ARDS was informed primarily by observational data. In 2012, a meta-analysis comparing LTVV with “conventional” VT (10-12 mL/kg IBW) in non-ARDS patients found that those given LTVV had a lower incidence of acute lung injury and lower overall mortality (Neto AS, et al. JAMA. 2012 308[16]:1651). While these were promising findings, there was limited follow-up poststudy onset, and the majority of included studies were based on a surgical population. Additionally, the use of VT > 10 mL/kg PBW has become uncommon in routine clinical practice. How comparable are those previous studies to today’s clinical milieu? When comparing outcomes for ICU patients who were ventilated with low (≤7mL/kg PBW), intermediate (>7, but <10 mL/kg PBW), and high (≥10 mL/kg PBW) VT, a second meta-analysis found a 28% risk reduction in the development of ARDS or pneumonia with low vs high, but the similar difference was not seen when comparing low vs intermediate groups (Neto AS, et al. Crit Care Med. 2015;43[10]:2155). This research suggested that negative outcomes were driven by the excessive VT.

To investigate the importance of timing of LTVV in ARDS, Needham and colleagues performed a prospective cohort study in patients with ARDS, examining the effect of VT received over time on the outcome of ICU mortality (Needham DM, et al. Am J Respir Crit Care Med. 2015;191[2]:177). They found that every 1 mL/kg increase in VT setting was associated with a 23% increase in mortality and, indeed, increases in subsequent VT compared with baseline setting were associated with increasing mortality. One may, therefore, be concerned that if we miss the ARDS diagnosis, the default to higher VT at the time of intubation may harm our patients. With or without clinician recognition of ARDS, LUNG SAFE revealed that the average VT for the patients with confirmed ARDS was 7.6 (95% CI 7.5-7.7) mL/kg PBW. While this mean value is well within the range of lung protective ventilation (less than 8 mL/kg PBW), over one-third of patients were exposed to larger VT. A recently published study by Sjoding and colleagues showed that VT of >8 mL/kg PBW was used in 40% of the cohort, and continued exposure to 24 total hours of these high VT was associated with increased risk of mortality (OR 1.82 (95% CI, 1.20–2.78) (Sjoding MW, et al. Crit Care Med. 2019;47[1]:56). All three studies support early administration of lung protective ventilation, considering the high mortality associated with ARDS.

Before consolidating what we know about empiric use of LTVV, we also must highlight the important concerns about LTVV that were investigated in the PReVENT trial. Over-sedation to maintain low VT, increased delirium, ventilator asynchrony, and possibility of effort-induced lung injury are some of the potential risks associated with LTVV. While there were no differences in the use of sedatives or neuromuscular blocking agents between groups in the PReVENT trial, more delirium was seen in the LTVV group with a P = .06, which may be a signal deserving further exploration.

Therefore, now understanding both the upside and downside of LTVV, what’s our best approach? While we lack prospective clinical trial data showing benefit of LTVV in patients without ARDS, we do not have conclusive evidence to show its harm. Remembering that even intensivists can fail to recognize ARDS at its onset, default utilization of LTVV, or at least lung protective ventilation of <8 mL/kg PBW, may be the safest approach for all patients. To be clear, this approach would still allow for active physician decision-making to personalize the settings to the individual patient’s needs, including the use of higher VT if needed for patient comfort, effort, and sedation needs. Changing the default settings and implementing friendly reminders about how to manage the ventilator has already been shown to be helpful for the surgical population (O’Reilly-Shah VN, et al. BMJ Qual Saf. 2018;27[12]:1008).

We must also consider the process of health-care delivery and the implementation of best practices, after considering the facilitators and barriers to adoption of said practices. Many patients decompensate and require intubation prior to ICU arrival, with prolonged boarding in the ED or medical wards being a common occurrence for many hospitals. As such, we need to consider a ventilation strategy that allows for best practice implementation at a hospital-wide level, appealing to an interprofessional approach to ventilator management, employing physicians outside of critical care medicine, respiratory therapists, and nursing. The PReVENT trial had a nicely constructed protocol with clear instructions on ventilator adjustments with frequent plateau pressure measurements and patient assessments. In the real world setting, especially in a non-ICU setting, ventilator management is not as straightforward. Considering that plateau pressures were only checked in approximately 40% of the patients in LUNG SAFE cohort, active management and attention to driving pressure may be a stretch in many settings.

Until we get 100% sensitive in timely recognition (instantaneous, really) of ARDS pathology augmented by automated diagnostic tools embedded in the medical record and/or incorporate advanced technology in the ventilator management to avoid human error, employing simple defaults to guarantee a protective setting in case of later diagnosis of ARDS seems logical. We can even go further to separate the defaults into LTVV for hypoxemic respiratory failure and lung protective ventilation for everything else, with future development of more algorithms, protocols, and clinical decision support tools for ventilator management. For the time being, a simpler intervention of setting a safer default is a great universal start.

Dr. Mathews and Dr. Howell are with the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine; Dr. Mathews is also with the Department of Emergency Medicine; Icahn School of Medicine at Mount Sinai, New York, NY.

Since the landmark ARMA trial, use of low tidal volume ventilation (LTVV) at 6 mL/kg predicted body weight (PBW) has become our gold standard for ventilator management in acute respiratory distress syndrome (ARDS) (Brower RG, et al. N Engl J Med. 2000;342[18]:1301). While other studies have suggested that patients without ARDS may also benefit from lower volumes, the recently published Protective Ventilation in Patients Without ARDS (PReVENT) trial found no benefit to using LTVV in non-ARDS patients (Simonis FD, et al. JAMA. 2018;320[18]:1872). Does this mean we let physicians set volumes at will? Is tidal volume (VT) even clinically relevant anymore in the non-ARDS population?

Prior to the PReVENT trial, our practice of LTVV for patients without ARDS was informed primarily by observational data. In 2012, a meta-analysis comparing LTVV with “conventional” VT (10-12 mL/kg IBW) in non-ARDS patients found that those given LTVV had a lower incidence of acute lung injury and lower overall mortality (Neto AS, et al. JAMA. 2012 308[16]:1651). While these were promising findings, there was limited follow-up poststudy onset, and the majority of included studies were based on a surgical population. Additionally, the use of VT > 10 mL/kg PBW has become uncommon in routine clinical practice. How comparable are those previous studies to today’s clinical milieu? When comparing outcomes for ICU patients who were ventilated with low (≤7mL/kg PBW), intermediate (>7, but <10 mL/kg PBW), and high (≥10 mL/kg PBW) VT, a second meta-analysis found a 28% risk reduction in the development of ARDS or pneumonia with low vs high, but the similar difference was not seen when comparing low vs intermediate groups (Neto AS, et al. Crit Care Med. 2015;43[10]:2155). This research suggested that negative outcomes were driven by the excessive VT.

To investigate the importance of timing of LTVV in ARDS, Needham and colleagues performed a prospective cohort study in patients with ARDS, examining the effect of VT received over time on the outcome of ICU mortality (Needham DM, et al. Am J Respir Crit Care Med. 2015;191[2]:177). They found that every 1 mL/kg increase in VT setting was associated with a 23% increase in mortality and, indeed, increases in subsequent VT compared with baseline setting were associated with increasing mortality. One may, therefore, be concerned that if we miss the ARDS diagnosis, the default to higher VT at the time of intubation may harm our patients. With or without clinician recognition of ARDS, LUNG SAFE revealed that the average VT for the patients with confirmed ARDS was 7.6 (95% CI 7.5-7.7) mL/kg PBW. While this mean value is well within the range of lung protective ventilation (less than 8 mL/kg PBW), over one-third of patients were exposed to larger VT. A recently published study by Sjoding and colleagues showed that VT of >8 mL/kg PBW was used in 40% of the cohort, and continued exposure to 24 total hours of these high VT was associated with increased risk of mortality (OR 1.82 (95% CI, 1.20–2.78) (Sjoding MW, et al. Crit Care Med. 2019;47[1]:56). All three studies support early administration of lung protective ventilation, considering the high mortality associated with ARDS.

Before consolidating what we know about empiric use of LTVV, we also must highlight the important concerns about LTVV that were investigated in the PReVENT trial. Over-sedation to maintain low VT, increased delirium, ventilator asynchrony, and possibility of effort-induced lung injury are some of the potential risks associated with LTVV. While there were no differences in the use of sedatives or neuromuscular blocking agents between groups in the PReVENT trial, more delirium was seen in the LTVV group with a P = .06, which may be a signal deserving further exploration.

Therefore, now understanding both the upside and downside of LTVV, what’s our best approach? While we lack prospective clinical trial data showing benefit of LTVV in patients without ARDS, we do not have conclusive evidence to show its harm. Remembering that even intensivists can fail to recognize ARDS at its onset, default utilization of LTVV, or at least lung protective ventilation of <8 mL/kg PBW, may be the safest approach for all patients. To be clear, this approach would still allow for active physician decision-making to personalize the settings to the individual patient’s needs, including the use of higher VT if needed for patient comfort, effort, and sedation needs. Changing the default settings and implementing friendly reminders about how to manage the ventilator has already been shown to be helpful for the surgical population (O’Reilly-Shah VN, et al. BMJ Qual Saf. 2018;27[12]:1008).

We must also consider the process of health-care delivery and the implementation of best practices, after considering the facilitators and barriers to adoption of said practices. Many patients decompensate and require intubation prior to ICU arrival, with prolonged boarding in the ED or medical wards being a common occurrence for many hospitals. As such, we need to consider a ventilation strategy that allows for best practice implementation at a hospital-wide level, appealing to an interprofessional approach to ventilator management, employing physicians outside of critical care medicine, respiratory therapists, and nursing. The PReVENT trial had a nicely constructed protocol with clear instructions on ventilator adjustments with frequent plateau pressure measurements and patient assessments. In the real world setting, especially in a non-ICU setting, ventilator management is not as straightforward. Considering that plateau pressures were only checked in approximately 40% of the patients in LUNG SAFE cohort, active management and attention to driving pressure may be a stretch in many settings.

Until we get 100% sensitive in timely recognition (instantaneous, really) of ARDS pathology augmented by automated diagnostic tools embedded in the medical record and/or incorporate advanced technology in the ventilator management to avoid human error, employing simple defaults to guarantee a protective setting in case of later diagnosis of ARDS seems logical. We can even go further to separate the defaults into LTVV for hypoxemic respiratory failure and lung protective ventilation for everything else, with future development of more algorithms, protocols, and clinical decision support tools for ventilator management. For the time being, a simpler intervention of setting a safer default is a great universal start.

Dr. Mathews and Dr. Howell are with the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine; Dr. Mathews is also with the Department of Emergency Medicine; Icahn School of Medicine at Mount Sinai, New York, NY.

Since the landmark ARMA trial, use of low tidal volume ventilation (LTVV) at 6 mL/kg predicted body weight (PBW) has become our gold standard for ventilator management in acute respiratory distress syndrome (ARDS) (Brower RG, et al. N Engl J Med. 2000;342[18]:1301). While other studies have suggested that patients without ARDS may also benefit from lower volumes, the recently published Protective Ventilation in Patients Without ARDS (PReVENT) trial found no benefit to using LTVV in non-ARDS patients (Simonis FD, et al. JAMA. 2018;320[18]:1872). Does this mean we let physicians set volumes at will? Is tidal volume (VT) even clinically relevant anymore in the non-ARDS population?

Prior to the PReVENT trial, our practice of LTVV for patients without ARDS was informed primarily by observational data. In 2012, a meta-analysis comparing LTVV with “conventional” VT (10-12 mL/kg IBW) in non-ARDS patients found that those given LTVV had a lower incidence of acute lung injury and lower overall mortality (Neto AS, et al. JAMA. 2012 308[16]:1651). While these were promising findings, there was limited follow-up poststudy onset, and the majority of included studies were based on a surgical population. Additionally, the use of VT > 10 mL/kg PBW has become uncommon in routine clinical practice. How comparable are those previous studies to today’s clinical milieu? When comparing outcomes for ICU patients who were ventilated with low (≤7mL/kg PBW), intermediate (>7, but <10 mL/kg PBW), and high (≥10 mL/kg PBW) VT, a second meta-analysis found a 28% risk reduction in the development of ARDS or pneumonia with low vs high, but the similar difference was not seen when comparing low vs intermediate groups (Neto AS, et al. Crit Care Med. 2015;43[10]:2155). This research suggested that negative outcomes were driven by the excessive VT.

To investigate the importance of timing of LTVV in ARDS, Needham and colleagues performed a prospective cohort study in patients with ARDS, examining the effect of VT received over time on the outcome of ICU mortality (Needham DM, et al. Am J Respir Crit Care Med. 2015;191[2]:177). They found that every 1 mL/kg increase in VT setting was associated with a 23% increase in mortality and, indeed, increases in subsequent VT compared with baseline setting were associated with increasing mortality. One may, therefore, be concerned that if we miss the ARDS diagnosis, the default to higher VT at the time of intubation may harm our patients. With or without clinician recognition of ARDS, LUNG SAFE revealed that the average VT for the patients with confirmed ARDS was 7.6 (95% CI 7.5-7.7) mL/kg PBW. While this mean value is well within the range of lung protective ventilation (less than 8 mL/kg PBW), over one-third of patients were exposed to larger VT. A recently published study by Sjoding and colleagues showed that VT of >8 mL/kg PBW was used in 40% of the cohort, and continued exposure to 24 total hours of these high VT was associated with increased risk of mortality (OR 1.82 (95% CI, 1.20–2.78) (Sjoding MW, et al. Crit Care Med. 2019;47[1]:56). All three studies support early administration of lung protective ventilation, considering the high mortality associated with ARDS.

Before consolidating what we know about empiric use of LTVV, we also must highlight the important concerns about LTVV that were investigated in the PReVENT trial. Over-sedation to maintain low VT, increased delirium, ventilator asynchrony, and possibility of effort-induced lung injury are some of the potential risks associated with LTVV. While there were no differences in the use of sedatives or neuromuscular blocking agents between groups in the PReVENT trial, more delirium was seen in the LTVV group with a P = .06, which may be a signal deserving further exploration.

Therefore, now understanding both the upside and downside of LTVV, what’s our best approach? While we lack prospective clinical trial data showing benefit of LTVV in patients without ARDS, we do not have conclusive evidence to show its harm. Remembering that even intensivists can fail to recognize ARDS at its onset, default utilization of LTVV, or at least lung protective ventilation of <8 mL/kg PBW, may be the safest approach for all patients. To be clear, this approach would still allow for active physician decision-making to personalize the settings to the individual patient’s needs, including the use of higher VT if needed for patient comfort, effort, and sedation needs. Changing the default settings and implementing friendly reminders about how to manage the ventilator has already been shown to be helpful for the surgical population (O’Reilly-Shah VN, et al. BMJ Qual Saf. 2018;27[12]:1008).

We must also consider the process of health-care delivery and the implementation of best practices, after considering the facilitators and barriers to adoption of said practices. Many patients decompensate and require intubation prior to ICU arrival, with prolonged boarding in the ED or medical wards being a common occurrence for many hospitals. As such, we need to consider a ventilation strategy that allows for best practice implementation at a hospital-wide level, appealing to an interprofessional approach to ventilator management, employing physicians outside of critical care medicine, respiratory therapists, and nursing. The PReVENT trial had a nicely constructed protocol with clear instructions on ventilator adjustments with frequent plateau pressure measurements and patient assessments. In the real world setting, especially in a non-ICU setting, ventilator management is not as straightforward. Considering that plateau pressures were only checked in approximately 40% of the patients in LUNG SAFE cohort, active management and attention to driving pressure may be a stretch in many settings.

Until we get 100% sensitive in timely recognition (instantaneous, really) of ARDS pathology augmented by automated diagnostic tools embedded in the medical record and/or incorporate advanced technology in the ventilator management to avoid human error, employing simple defaults to guarantee a protective setting in case of later diagnosis of ARDS seems logical. We can even go further to separate the defaults into LTVV for hypoxemic respiratory failure and lung protective ventilation for everything else, with future development of more algorithms, protocols, and clinical decision support tools for ventilator management. For the time being, a simpler intervention of setting a safer default is a great universal start.

Dr. Mathews and Dr. Howell are with the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine; Dr. Mathews is also with the Department of Emergency Medicine; Icahn School of Medicine at Mount Sinai, New York, NY.

Michelle Cao, DO, FCCP

Dr. Michelle Cao is a Clinical Associate Professor in the Division of Sleep Medicine and Division of Neuromuscular Medicine, at the Stanford University School of Medicine. Her clinical expertise is in complex sleep-related respiratory disorders and home mechanical ventilation for chronic respiratory failure syndromes. She oversees the Noninvasive Ventilation Program for the Stanford Neuromuscular Medicine Center. Dr. Cao also holds the position of Vice-Chair for the Home-Based Mechanical Ventilation and Neuromuscular Disease NetWork with CHEST and is a member of the Scientific Presentations and Awards Committee.

Michelle Cao, DO, FCCP

Dr. Michelle Cao is a Clinical Associate Professor in the Division of Sleep Medicine and Division of Neuromuscular Medicine, at the Stanford University School of Medicine. Her clinical expertise is in complex sleep-related respiratory disorders and home mechanical ventilation for chronic respiratory failure syndromes. She oversees the Noninvasive Ventilation Program for the Stanford Neuromuscular Medicine Center. Dr. Cao also holds the position of Vice-Chair for the Home-Based Mechanical Ventilation and Neuromuscular Disease NetWork with CHEST and is a member of the Scientific Presentations and Awards Committee.

Michelle Cao, DO, FCCP

Dr. Michelle Cao is a Clinical Associate Professor in the Division of Sleep Medicine and Division of Neuromuscular Medicine, at the Stanford University School of Medicine. Her clinical expertise is in complex sleep-related respiratory disorders and home mechanical ventilation for chronic respiratory failure syndromes. She oversees the Noninvasive Ventilation Program for the Stanford Neuromuscular Medicine Center. Dr. Cao also holds the position of Vice-Chair for the Home-Based Mechanical Ventilation and Neuromuscular Disease NetWork with CHEST and is a member of the Scientific Presentations and Awards Committee.

We are so excited to once again host the NetWorks Challenge. During the next 3 months, you have the opportunity to be a Champion and make a donation to the CHEST Foundation. Every time you contribute, you can designate a NetWork of your choice to benefit from your gift. Each NetWork is eligible to receive travel grants to CHEST 2019 based on the amount raised. Last year, we more than doubled the number of early career clinician travel grants to attend CHEST 2018. This year, we want to raise the bar again. Don’t delay, make a donation today by visiting Chestfoundation.org/donate and be a Champion for your NetWork!

Length: This year, the NetWorks Challenge will span 3 months. Contributions made between April 1 and June 30 count toward your NetWork’s fundraising total! Just be sure to list your NetWork when making your contribution on chestfoundation.org/donate. Additionally, any contributions made to the CHEST Foundation during your membership renewal will count toward your NetWorks total amount raised - no matter when your membership is up for renewal. Contributions made in this manner after June 30 will count toward your Network’s 2020 amount raised.

We are so excited to once again host the NetWorks Challenge. During the next 3 months, you have the opportunity to be a Champion and make a donation to the CHEST Foundation. Every time you contribute, you can designate a NetWork of your choice to benefit from your gift. Each NetWork is eligible to receive travel grants to CHEST 2019 based on the amount raised. Last year, we more than doubled the number of early career clinician travel grants to attend CHEST 2018. This year, we want to raise the bar again. Don’t delay, make a donation today by visiting Chestfoundation.org/donate and be a Champion for your NetWork!

Length: This year, the NetWorks Challenge will span 3 months. Contributions made between April 1 and June 30 count toward your NetWork’s fundraising total! Just be sure to list your NetWork when making your contribution on chestfoundation.org/donate. Additionally, any contributions made to the CHEST Foundation during your membership renewal will count toward your NetWorks total amount raised - no matter when your membership is up for renewal. Contributions made in this manner after June 30 will count toward your Network’s 2020 amount raised.

We are so excited to once again host the NetWorks Challenge. During the next 3 months, you have the opportunity to be a Champion and make a donation to the CHEST Foundation. Every time you contribute, you can designate a NetWork of your choice to benefit from your gift. Each NetWork is eligible to receive travel grants to CHEST 2019 based on the amount raised. Last year, we more than doubled the number of early career clinician travel grants to attend CHEST 2018. This year, we want to raise the bar again. Don’t delay, make a donation today by visiting Chestfoundation.org/donate and be a Champion for your NetWork!

Length: This year, the NetWorks Challenge will span 3 months. Contributions made between April 1 and June 30 count toward your NetWork’s fundraising total! Just be sure to list your NetWork when making your contribution on chestfoundation.org/donate. Additionally, any contributions made to the CHEST Foundation during your membership renewal will count toward your NetWorks total amount raised - no matter when your membership is up for renewal. Contributions made in this manner after June 30 will count toward your Network’s 2020 amount raised.

While CHEST 2019 will have your days busy, don’t forget to find time to explore entertaining, cultural, and historic places around New Orleans. Grab your friends and colleagues for some fun, and try out a few of these places!

1. House of Blues New Orleans

If you’re already heading to the city known for jazz and blues, there’s no better place to experience that than the House of Blues New Orleans. Enjoy live music and great food under one roof. Be sure to check the House of Blues website as the annual meeting draws nearer to see which concerts and events will be happening in October.



2. Audubon Aquarium of the Americas

Located just north of the convention center, head over to the Audubon Aquarium of the Americas. During the fall and winter months, the aquarium has less traffic, which allows you to take in all the animals and exhibits at your own pace. See exhibits like the Great Maya Reef, a walk-through tunnel into a submerged Maya city of the Yucatan peninsula; the penguins, sea otters, or the sharks and rays in the 400,000-gallon Gulf of Mexico Exhibit.



Hours: Monday - Sunday | 10 AM - 5 PM

While CHEST 2019 will have your days busy, don’t forget to find time to explore entertaining, cultural, and historic places around New Orleans. Grab your friends and colleagues for some fun, and try out a few of these places!

1. House of Blues New Orleans

If you’re already heading to the city known for jazz and blues, there’s no better place to experience that than the House of Blues New Orleans. Enjoy live music and great food under one roof. Be sure to check the House of Blues website as the annual meeting draws nearer to see which concerts and events will be happening in October.



2. Audubon Aquarium of the Americas

Located just north of the convention center, head over to the Audubon Aquarium of the Americas. During the fall and winter months, the aquarium has less traffic, which allows you to take in all the animals and exhibits at your own pace. See exhibits like the Great Maya Reef, a walk-through tunnel into a submerged Maya city of the Yucatan peninsula; the penguins, sea otters, or the sharks and rays in the 400,000-gallon Gulf of Mexico Exhibit.



Hours: Monday - Sunday | 10 AM - 5 PM

While CHEST 2019 will have your days busy, don’t forget to find time to explore entertaining, cultural, and historic places around New Orleans. Grab your friends and colleagues for some fun, and try out a few of these places!

1. House of Blues New Orleans

If you’re already heading to the city known for jazz and blues, there’s no better place to experience that than the House of Blues New Orleans. Enjoy live music and great food under one roof. Be sure to check the House of Blues website as the annual meeting draws nearer to see which concerts and events will be happening in October.



2. Audubon Aquarium of the Americas

Located just north of the convention center, head over to the Audubon Aquarium of the Americas. During the fall and winter months, the aquarium has less traffic, which allows you to take in all the animals and exhibits at your own pace. See exhibits like the Great Maya Reef, a walk-through tunnel into a submerged Maya city of the Yucatan peninsula; the penguins, sea otters, or the sharks and rays in the 400,000-gallon Gulf of Mexico Exhibit.



Hours: Monday - Sunday | 10 AM - 5 PM

Sleep: It Does a Body Good by Dr. Nancy Stewart

Sleep: it does a body good. No really, it does. When asked to write this month’s blog on sleep for Sleep Awareness Month, although honored, it was somewhat comical because the night prior I had one of my worst nights of sleep in a long time, taking care of a sick child. As health-care providers, we often lead stressful lives and pack way too much into our schedules. Both the Centers for Disease Control and the American Academy of Sleep Medicine recommend obtaining 7 to 9 hours of sleep per night for adults; unfortunately, many of us are not getting the recommended 7 to 9 hours of sleep.

Find the entire blog at https://goo.gl/sp9wWn.


 

Sleep: It Does a Body Good by Dr. Nancy Stewart

Sleep: it does a body good. No really, it does. When asked to write this month’s blog on sleep for Sleep Awareness Month, although honored, it was somewhat comical because the night prior I had one of my worst nights of sleep in a long time, taking care of a sick child. As health-care providers, we often lead stressful lives and pack way too much into our schedules. Both the Centers for Disease Control and the American Academy of Sleep Medicine recommend obtaining 7 to 9 hours of sleep per night for adults; unfortunately, many of us are not getting the recommended 7 to 9 hours of sleep.

Find the entire blog at https://goo.gl/sp9wWn.


 

Sleep: It Does a Body Good by Dr. Nancy Stewart

Sleep: it does a body good. No really, it does. When asked to write this month’s blog on sleep for Sleep Awareness Month, although honored, it was somewhat comical because the night prior I had one of my worst nights of sleep in a long time, taking care of a sick child. As health-care providers, we often lead stressful lives and pack way too much into our schedules. Both the Centers for Disease Control and the American Academy of Sleep Medicine recommend obtaining 7 to 9 hours of sleep per night for adults; unfortunately, many of us are not getting the recommended 7 to 9 hours of sleep.

Find the entire blog at https://goo.gl/sp9wWn.


 

MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.

The Helping to End Addiction Long-term (HEAL) initiative has over $850 million in total obligated for fiscal year 2019, said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.

In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.

The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.

First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”

Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”

The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.

koakes@mdedge.com

MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.

The Helping to End Addiction Long-term (HEAL) initiative has over $850 million in total obligated for fiscal year 2019, said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.

In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.

The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.

First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”

Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”

The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.

koakes@mdedge.com

MILWAUKEE – Congress has allocated a half billion dollars annually to the National Institutes of Health for a program that seeks to end America’s opioid crisis. The agency is putting in place over two-dozen projects spanning basic and translational research, clinical trials, and implementation of new strategies to address pain and fight addiction.

The Helping to End Addiction Long-term (HEAL) initiative has over $850 million in total obligated for fiscal year 2019, said Walter Koroshetz, MD, speaking at the scientific meeting of the American Pain Society. This represents carryover from 2018, a planning year for the initiative, along with the 2019 $500 million annual supplement to the NIH’s base appropriation.

In 2018, NIH and other federal agencies successfully convinced Congress that funding a coordinated use of resources was necessary to overcome the country’s dual opioid and chronic pain crises. “Luck happens to the prepared,” said Dr. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, Md., adding that many hours went into putting together a national pain strategy that is multidisciplinary and multi-layered, and involves multiple players.

The two aims of research under the initiative are to improve treatments for misuse and addiction, and to enhance pain management. Focusing on this latter aim, Dr. Koroshetz said that the initiative has several research priorities to enhance pain management.

First, the biological basis for chronic pain needs to be understood in order to formulate effective therapies and interventions. “We need to understand the transition from acute to chronic pain,” he commented. “We need to see if we can learn about the risk factors for developing chronic pain; if we get really lucky, we might identify some biological markers” that identify who is at risk for this transition “in a high-risk acute pain situation.”

Next, a key request of industry and academia will be development of more drugs that avoid the dual-target program of opioids, which affect reward circuitry along with pain circuitry. “Drugs affecting the pain circuit and the reward circuit will always result in addiction” potential, said Dr. Koroshetz. “We’re still using drugs for pain from the poppy plant that were discovered 8,000 years ago.”

The hope with the HEAL initiative is to bring together academic centers with patient populations and research capabilities with industry, to accelerate moving nonaddictive treatments through to phase 3 trials.

koakes@mdedge.com