TBD Meeting (3296-19)

SAN DIEGO – Patients who develop sepsis in the hospital appear to be in greater risk for mortality than those who bring it with them, a new study suggests. Patients with hospital-onset sepsis were twice as likely to die as those infected in the outside world.

MDedge News/Randy Dotinga

“There could be some differences in quality of care that explains the difference in mortality,” said study lead author Chanu Rhee, MD, assistant professor of population medicine at Harvard Medical School, Boston, in a presentation about the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In an interview, Dr. Rhee said researchers launched the study to gain a greater understanding of the epidemiology of sepsis in the hospital. They relied on a new Centers for Disease Control and Prevention definition of sepsis that is “enhancing the consistency of surveillance across hospitals and allowing more precise differentiation between hospital-onset versus community-onset sepsis.”

The study authors retrospectively tracked more than 2.2 million patients who were treated at 136 U.S. hospitals from 2009 to 2015. In general, hospital-onset sepsis was defined as patients who had a blood culture, initial antibiotic therapy, and organ dysfunction on their third day in the hospital or later.*

Of the patients, 83,600 had community-onset sepsis and 11,500 had hospital-onset sepsis. Those with sepsis were more likely to be men and have comorbidities such as cancer, congestive heart failure, diabetes, and renal disease.

Patients with hospital-onset sepsis had longer median lengths of stay (19 days) than the community-onset group (8 days) and the no-sepsis group (4 days). The hospital-onset group also had a greater likelihood of ICU admission (61%) than the community-onset (44%) and no-sepsis (9%) groups.

About 34% of those with hospital-onset sepsis died, compared with 17% of the community-onset group and 2% of the patients who didn’t have sepsis. After adjustment, those with hospital-onset sepsis were still more likely to have died (odds ratio, 2.1; 95% confidence interval, 2.0-2.2).

“Other studies have suggested that there may be delays in the recognition and care of patients who develop sepsis in the hospital as opposed to presenting to the hospital with sepsis,” Dr. Rhee said. “It is also possible that hospital-onset sepsis tends to be caused by organisms that are more virulent and resistant to antibiotics.”

Overall, he said, “our findings underscore the importance of targeting hospital-onset sepsis with surveillance, prevention, and quality improvement efforts.”

The study was funded by the CDC and the Agency for Healthcare Research and Quality. The authors reported no relevant disclosures.

SOURCE: Rhee C et al. CCC48, Abstract 29.

*Correction, 3/19/19: An earlier version of this article misstated the definition of sepsis.

SAN DIEGO – Patients who develop sepsis in the hospital appear to be in greater risk for mortality than those who bring it with them, a new study suggests. Patients with hospital-onset sepsis were twice as likely to die as those infected in the outside world.

MDedge News/Randy Dotinga

“There could be some differences in quality of care that explains the difference in mortality,” said study lead author Chanu Rhee, MD, assistant professor of population medicine at Harvard Medical School, Boston, in a presentation about the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In an interview, Dr. Rhee said researchers launched the study to gain a greater understanding of the epidemiology of sepsis in the hospital. They relied on a new Centers for Disease Control and Prevention definition of sepsis that is “enhancing the consistency of surveillance across hospitals and allowing more precise differentiation between hospital-onset versus community-onset sepsis.”

The study authors retrospectively tracked more than 2.2 million patients who were treated at 136 U.S. hospitals from 2009 to 2015. In general, hospital-onset sepsis was defined as patients who had a blood culture, initial antibiotic therapy, and organ dysfunction on their third day in the hospital or later.*

Of the patients, 83,600 had community-onset sepsis and 11,500 had hospital-onset sepsis. Those with sepsis were more likely to be men and have comorbidities such as cancer, congestive heart failure, diabetes, and renal disease.

Patients with hospital-onset sepsis had longer median lengths of stay (19 days) than the community-onset group (8 days) and the no-sepsis group (4 days). The hospital-onset group also had a greater likelihood of ICU admission (61%) than the community-onset (44%) and no-sepsis (9%) groups.

About 34% of those with hospital-onset sepsis died, compared with 17% of the community-onset group and 2% of the patients who didn’t have sepsis. After adjustment, those with hospital-onset sepsis were still more likely to have died (odds ratio, 2.1; 95% confidence interval, 2.0-2.2).

“Other studies have suggested that there may be delays in the recognition and care of patients who develop sepsis in the hospital as opposed to presenting to the hospital with sepsis,” Dr. Rhee said. “It is also possible that hospital-onset sepsis tends to be caused by organisms that are more virulent and resistant to antibiotics.”

Overall, he said, “our findings underscore the importance of targeting hospital-onset sepsis with surveillance, prevention, and quality improvement efforts.”

The study was funded by the CDC and the Agency for Healthcare Research and Quality. The authors reported no relevant disclosures.

SOURCE: Rhee C et al. CCC48, Abstract 29.

*Correction, 3/19/19: An earlier version of this article misstated the definition of sepsis.

SAN DIEGO – Patients who develop sepsis in the hospital appear to be in greater risk for mortality than those who bring it with them, a new study suggests. Patients with hospital-onset sepsis were twice as likely to die as those infected in the outside world.

MDedge News/Randy Dotinga

“There could be some differences in quality of care that explains the difference in mortality,” said study lead author Chanu Rhee, MD, assistant professor of population medicine at Harvard Medical School, Boston, in a presentation about the findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

In an interview, Dr. Rhee said researchers launched the study to gain a greater understanding of the epidemiology of sepsis in the hospital. They relied on a new Centers for Disease Control and Prevention definition of sepsis that is “enhancing the consistency of surveillance across hospitals and allowing more precise differentiation between hospital-onset versus community-onset sepsis.”

The study authors retrospectively tracked more than 2.2 million patients who were treated at 136 U.S. hospitals from 2009 to 2015. In general, hospital-onset sepsis was defined as patients who had a blood culture, initial antibiotic therapy, and organ dysfunction on their third day in the hospital or later.*

Of the patients, 83,600 had community-onset sepsis and 11,500 had hospital-onset sepsis. Those with sepsis were more likely to be men and have comorbidities such as cancer, congestive heart failure, diabetes, and renal disease.

Patients with hospital-onset sepsis had longer median lengths of stay (19 days) than the community-onset group (8 days) and the no-sepsis group (4 days). The hospital-onset group also had a greater likelihood of ICU admission (61%) than the community-onset (44%) and no-sepsis (9%) groups.

About 34% of those with hospital-onset sepsis died, compared with 17% of the community-onset group and 2% of the patients who didn’t have sepsis. After adjustment, those with hospital-onset sepsis were still more likely to have died (odds ratio, 2.1; 95% confidence interval, 2.0-2.2).

“Other studies have suggested that there may be delays in the recognition and care of patients who develop sepsis in the hospital as opposed to presenting to the hospital with sepsis,” Dr. Rhee said. “It is also possible that hospital-onset sepsis tends to be caused by organisms that are more virulent and resistant to antibiotics.”

Overall, he said, “our findings underscore the importance of targeting hospital-onset sepsis with surveillance, prevention, and quality improvement efforts.”

The study was funded by the CDC and the Agency for Healthcare Research and Quality. The authors reported no relevant disclosures.

SOURCE: Rhee C et al. CCC48, Abstract 29.

*Correction, 3/19/19: An earlier version of this article misstated the definition of sepsis.

SAN DIEGO – North Carolina health care workers often failed to provide best-practice follow-up to patients who were released after hospitalization for sepsis, a small study has found. There may be a cost to this gap: Patients who received recommended postsepsis care were less likely to die or be readmitted within 90 days.

“It’s disappointing to see that we are not providing these seemingly common-sense care processes to our sepsis patients at discharge,” said study lead author Stephanie Parks Taylor, MD, of Atrium Health’s Carolinas Medical Center in Charlotte, in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “We need to develop and implement strategies to improve outcomes for sepsis patients, not just while they are in the hospital, but after discharge as well.”

A 2017 report estimated that 1.7 million adults were hospitalized for sepsis in the United States in 2014, and 270,000 died (JAMA. 2017;318[13]:1241-9). Age-adjusted sepsis death rates in the United States are highest in states in the Eastern and Southern regions, a 2017 report from the Centers for Disease Control and Prevention suggested; North Carolina has the 32nd-worst sepsis death rate in the country (12.4 deaths per 100,000 population).

Dr. Taylor said some recent news about sepsis is promising. “We’ve seen decreasing mortality rates from initiatives that improve the early detection of sepsis and rapid delivery of antibiotics, fluids, and other treatment. However, there is growing evidence that patients who survive an episode of sepsis face residual health deficits. Many sepsis survivors are left with new functional, cognitive, or mental health declines or worsening of their underlying comorbidities. Unfortunately, these patients have high rates of mortality and hospital readmission that persist for multiple years after hospitalization.”

Indeed, a 2013 report linked sepsis to significantly higher mortality risk over 5 years, after accounting for comorbidities. Postsepsis patients were 13 times more likely to die over the first year after hospitalization than counterparts who didn’t have sepsis (BMJ Open. 2014;4:e004283).

For the new study, Dr. Taylor said, “we aimed to evaluate current care practices with the hope to identify a postsepsis management strategy that could help nudge these patients towards a more meaningful recovery.”

The researchers retrospectively tracked a random sample of 100 patients (median age, 63 years), who were discharged following an admission for sepsis in 2017. They were treated at eight acute care hospitals in western and central North Carolina and hospitalized for a median of 5 days; 75 were discharged to home (17 received home health services there), 17 went to skilled nursing or long-term care facilities, and 8 went to hospice or another location.

The researchers analyzed whether the patients received four kinds of postsepsis care within 90 days, as recommended by a 2018 review: screening for common functional impairments (53/100 patients received this screening); adjustment of medications as needed following discharge (53/100 patients); monitoring for common and preventable causes for health deterioration, such as infection, chronic lung disease, or heart failure exacerbation (37/100); and assessment for palliative care (25/100 patients) (JAMA. 2018;319[1]:62-75).

Within 90 days of discharge, 34 patients were readmitted and 17 died. The 32 patients who received at least two recommended kinds of postsepsis care were less likely to be readmitted or die (9/32) than those who got zero or one recommended kind of care (34/68; odds ratio, 0.26; 95% confidence ratio, 0.09-0.82).

In an interview, study coauthor Marc Kowalkowski, PhD, associate professor with Atrium Health’s Center for Outcomes Research and Evaluation, said he was hesitant to only allocate blame to hospitals or outpatient providers. “Transition out of the hospital is an extremely complex event, involving often fragmented care settings, and sepsis patients tend to be more complicated than other patients. It probably makes sense to provide an added layer of support during the transition out of the hospital for patients who are at high risk for poor outcomes.”

Overall, the findings are “a call for clinicians to realize sepsis is more than just an acute illness. The combination of a growing number of sepsis survivors and the increased health problems following an episode of sepsis creates an urgent public health challenge,” Dr. Taylor said.

Is more home health an important part of a solution? It may be helpful, Dr. Taylor said, but “our data suggest that there really needs to be better coordination to bridge between the inpatient and outpatient transition. We are currently conducting a randomized study to investigate whether these types of care processes can be delivered effectively through a nurse navigator to improve patient outcomes.”

Fortunately, she said, the findings suggest “we don’t have to reinvent the wheel. We just have to work on implementation of strategies for care processes that we are already familiar with.”

No funding was reported. None of the study authors reported relevant disclosures.

SOURCE: Taylor SP et al. CCC48, Abstract 1320.

SAN DIEGO – North Carolina health care workers often failed to provide best-practice follow-up to patients who were released after hospitalization for sepsis, a small study has found. There may be a cost to this gap: Patients who received recommended postsepsis care were less likely to die or be readmitted within 90 days.

“It’s disappointing to see that we are not providing these seemingly common-sense care processes to our sepsis patients at discharge,” said study lead author Stephanie Parks Taylor, MD, of Atrium Health’s Carolinas Medical Center in Charlotte, in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “We need to develop and implement strategies to improve outcomes for sepsis patients, not just while they are in the hospital, but after discharge as well.”

A 2017 report estimated that 1.7 million adults were hospitalized for sepsis in the United States in 2014, and 270,000 died (JAMA. 2017;318[13]:1241-9). Age-adjusted sepsis death rates in the United States are highest in states in the Eastern and Southern regions, a 2017 report from the Centers for Disease Control and Prevention suggested; North Carolina has the 32nd-worst sepsis death rate in the country (12.4 deaths per 100,000 population).

Dr. Taylor said some recent news about sepsis is promising. “We’ve seen decreasing mortality rates from initiatives that improve the early detection of sepsis and rapid delivery of antibiotics, fluids, and other treatment. However, there is growing evidence that patients who survive an episode of sepsis face residual health deficits. Many sepsis survivors are left with new functional, cognitive, or mental health declines or worsening of their underlying comorbidities. Unfortunately, these patients have high rates of mortality and hospital readmission that persist for multiple years after hospitalization.”

Indeed, a 2013 report linked sepsis to significantly higher mortality risk over 5 years, after accounting for comorbidities. Postsepsis patients were 13 times more likely to die over the first year after hospitalization than counterparts who didn’t have sepsis (BMJ Open. 2014;4:e004283).

For the new study, Dr. Taylor said, “we aimed to evaluate current care practices with the hope to identify a postsepsis management strategy that could help nudge these patients towards a more meaningful recovery.”

The researchers retrospectively tracked a random sample of 100 patients (median age, 63 years), who were discharged following an admission for sepsis in 2017. They were treated at eight acute care hospitals in western and central North Carolina and hospitalized for a median of 5 days; 75 were discharged to home (17 received home health services there), 17 went to skilled nursing or long-term care facilities, and 8 went to hospice or another location.

The researchers analyzed whether the patients received four kinds of postsepsis care within 90 days, as recommended by a 2018 review: screening for common functional impairments (53/100 patients received this screening); adjustment of medications as needed following discharge (53/100 patients); monitoring for common and preventable causes for health deterioration, such as infection, chronic lung disease, or heart failure exacerbation (37/100); and assessment for palliative care (25/100 patients) (JAMA. 2018;319[1]:62-75).

Within 90 days of discharge, 34 patients were readmitted and 17 died. The 32 patients who received at least two recommended kinds of postsepsis care were less likely to be readmitted or die (9/32) than those who got zero or one recommended kind of care (34/68; odds ratio, 0.26; 95% confidence ratio, 0.09-0.82).

In an interview, study coauthor Marc Kowalkowski, PhD, associate professor with Atrium Health’s Center for Outcomes Research and Evaluation, said he was hesitant to only allocate blame to hospitals or outpatient providers. “Transition out of the hospital is an extremely complex event, involving often fragmented care settings, and sepsis patients tend to be more complicated than other patients. It probably makes sense to provide an added layer of support during the transition out of the hospital for patients who are at high risk for poor outcomes.”

Overall, the findings are “a call for clinicians to realize sepsis is more than just an acute illness. The combination of a growing number of sepsis survivors and the increased health problems following an episode of sepsis creates an urgent public health challenge,” Dr. Taylor said.

Is more home health an important part of a solution? It may be helpful, Dr. Taylor said, but “our data suggest that there really needs to be better coordination to bridge between the inpatient and outpatient transition. We are currently conducting a randomized study to investigate whether these types of care processes can be delivered effectively through a nurse navigator to improve patient outcomes.”

Fortunately, she said, the findings suggest “we don’t have to reinvent the wheel. We just have to work on implementation of strategies for care processes that we are already familiar with.”

No funding was reported. None of the study authors reported relevant disclosures.

SOURCE: Taylor SP et al. CCC48, Abstract 1320.

SAN DIEGO – North Carolina health care workers often failed to provide best-practice follow-up to patients who were released after hospitalization for sepsis, a small study has found. There may be a cost to this gap: Patients who received recommended postsepsis care were less likely to die or be readmitted within 90 days.

“It’s disappointing to see that we are not providing these seemingly common-sense care processes to our sepsis patients at discharge,” said study lead author Stephanie Parks Taylor, MD, of Atrium Health’s Carolinas Medical Center in Charlotte, in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “We need to develop and implement strategies to improve outcomes for sepsis patients, not just while they are in the hospital, but after discharge as well.”

A 2017 report estimated that 1.7 million adults were hospitalized for sepsis in the United States in 2014, and 270,000 died (JAMA. 2017;318[13]:1241-9). Age-adjusted sepsis death rates in the United States are highest in states in the Eastern and Southern regions, a 2017 report from the Centers for Disease Control and Prevention suggested; North Carolina has the 32nd-worst sepsis death rate in the country (12.4 deaths per 100,000 population).

Dr. Taylor said some recent news about sepsis is promising. “We’ve seen decreasing mortality rates from initiatives that improve the early detection of sepsis and rapid delivery of antibiotics, fluids, and other treatment. However, there is growing evidence that patients who survive an episode of sepsis face residual health deficits. Many sepsis survivors are left with new functional, cognitive, or mental health declines or worsening of their underlying comorbidities. Unfortunately, these patients have high rates of mortality and hospital readmission that persist for multiple years after hospitalization.”

Indeed, a 2013 report linked sepsis to significantly higher mortality risk over 5 years, after accounting for comorbidities. Postsepsis patients were 13 times more likely to die over the first year after hospitalization than counterparts who didn’t have sepsis (BMJ Open. 2014;4:e004283).

For the new study, Dr. Taylor said, “we aimed to evaluate current care practices with the hope to identify a postsepsis management strategy that could help nudge these patients towards a more meaningful recovery.”

The researchers retrospectively tracked a random sample of 100 patients (median age, 63 years), who were discharged following an admission for sepsis in 2017. They were treated at eight acute care hospitals in western and central North Carolina and hospitalized for a median of 5 days; 75 were discharged to home (17 received home health services there), 17 went to skilled nursing or long-term care facilities, and 8 went to hospice or another location.

The researchers analyzed whether the patients received four kinds of postsepsis care within 90 days, as recommended by a 2018 review: screening for common functional impairments (53/100 patients received this screening); adjustment of medications as needed following discharge (53/100 patients); monitoring for common and preventable causes for health deterioration, such as infection, chronic lung disease, or heart failure exacerbation (37/100); and assessment for palliative care (25/100 patients) (JAMA. 2018;319[1]:62-75).

Within 90 days of discharge, 34 patients were readmitted and 17 died. The 32 patients who received at least two recommended kinds of postsepsis care were less likely to be readmitted or die (9/32) than those who got zero or one recommended kind of care (34/68; odds ratio, 0.26; 95% confidence ratio, 0.09-0.82).

In an interview, study coauthor Marc Kowalkowski, PhD, associate professor with Atrium Health’s Center for Outcomes Research and Evaluation, said he was hesitant to only allocate blame to hospitals or outpatient providers. “Transition out of the hospital is an extremely complex event, involving often fragmented care settings, and sepsis patients tend to be more complicated than other patients. It probably makes sense to provide an added layer of support during the transition out of the hospital for patients who are at high risk for poor outcomes.”

Overall, the findings are “a call for clinicians to realize sepsis is more than just an acute illness. The combination of a growing number of sepsis survivors and the increased health problems following an episode of sepsis creates an urgent public health challenge,” Dr. Taylor said.

Is more home health an important part of a solution? It may be helpful, Dr. Taylor said, but “our data suggest that there really needs to be better coordination to bridge between the inpatient and outpatient transition. We are currently conducting a randomized study to investigate whether these types of care processes can be delivered effectively through a nurse navigator to improve patient outcomes.”

Fortunately, she said, the findings suggest “we don’t have to reinvent the wheel. We just have to work on implementation of strategies for care processes that we are already familiar with.”

No funding was reported. None of the study authors reported relevant disclosures.

SOURCE: Taylor SP et al. CCC48, Abstract 1320.

SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

SAN DIEGO – Survivors of sepsis face ongoing challenges, including repeat hospitalizations for infections and repeat sepsis. Although it isn’t clear if such episodes result from incomplete resolution of the index infection, or they are due to lingering changes in immune function, they do suggest that physicians should engage sepsis patients in an effort to improve long-term outcomes.

Shawn Lockhart/CDC

It’s also an argument for biomarkers and precision immune modulation in these patients, Hallie Prescott, MD, a critical care physician at the VA Ann Arbor (Mich.) Healthcare System, said during a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

When sepsis was first defined in 1992, physicians tended to focus on the inflammatory component, but it’s now understood that multiple pathways become dysregulated, and inflammation is no longer part of the most current definition of sepsis. “We now recognize that there is early activation of both pro- and anti-inflammatory pathways, but over the course of sepsis the balance tips from this proinflammatory state in the first few days toward, for most patients, an anti-inflammatory or immune-suppressed state in the later days,” said Dr. Prescott.

As advances in care have increased initial survival rates, more patients go on to the later stages, leaving clinicians to address nosocomial and other secondary infections. An autopsy study showed that many patients who die of sepsis in the ICU have evidence of immune suppression. A study of patients at the end of a pneumonia hospitalization found that many patients had elevated inflammatory markers even after hospital discharge, and that such elevation was associated with increased mortality as far out as 1 year. The relationship was significant even after adjustment for age, comorbidity, and acute illness. “It suggests that this isn’t just identification of patients who had a more severe septic episode,” said Dr. Prescott.

That study implies that some patients take a long time to return to homeostasis, and other work suggests that about two-thirds of sepsis deaths occur after day 5. A study by Dr. Prescott’s group showed about a 40% 2-year mortality after sepsis hospitalization. When they compared sepsis survivors to matched controls, they found about half the deaths could not be explained by presepsis health status. “Rather, it [seems to be] due to the last sequelae of sepsis, or perhaps this increased risk of secondary infections,” Dr. Prescott said.

Studies of the organisms causing secondary infections found increasing incidence of opportunistic infections, from 9% in the first 5 days of sepsis, to 18% in days 16 through 150. The frequency of Candida infection similarly increased, from 13% to 30%. “So in these later phases of sepsis, you’re more likely to see [pathogens] that are relatively rare as the initial cause of sepsis,” said Dr. Prescott.

Unfortunately, several studies showed that prophylaxis does not improve outcomes. “My suspicion is that it’s because these infections are one marker of a broader problem with immune dysfunction, and we probably need to boost or restore immune function more broadly as opposed to trying to prophylax against very specifically what the patient is at risk for,” said Dr. Prescott.

The problems appear to continue after hospital discharge. A study from Dr. Prescott’s group showed that about 40% of sepsis survivors were readmitted at least once within the next 90 days. The most common reason, at 6.4%, was another sepsis episode. Compared with matched controls, sepsis patients had about a 2.5-fold higher risk for sepsis, and about a 1.5-fold increased risk an infection. “So there seems to be this heightened risk among people surviving sepsis that’s not fully explained by the things that put them at risk for developing sepsis in the first place,” said Dr. Prescott.

Another study looking at the reason for recurring infections in sepsis survivors found that in about one in five cases, the readmission was due to the same infectious organism in the same site, suggesting incomplete resolution. In about half of patients, the infection was due to a different organism, or the same organism at a different site, and in about a third of patients, the results were ambiguous due to culture-negative infections.

“I think this suggests a complex picture. Some people perhaps fail to fully eradicate the initial infection, and a larger group of people come back with something else. There’s also a very high rate of infection in the same site – about 70% with a new bug have it in the same site as their initial sepsis. Some of this may be just be a reflection of the type of people who get sepsis the first time, but it still tells us that among the patients we care for who survive sepsis, that they are over the long haul at increased risk of recurrent infections and recurrent episodes of sepsis,” said Dr. Prescott.

The findings suggest a need for real-time assessment of immune function and the potential benefit of immune modulation in the later phases of sepsis. Such strategies are not likely to be implemented immediately, however. In the meantime, there are simple steps that clinicians can take, including screening of sepsis survivors and making sure they are up to date on vaccines, and then educating them about the risk of reinfection. “We know that the lay public awareness of sepsis is low. Even people who have sepsis are often unaware that they had it, and they are certainly unaware that they’re at risk for having another episode,” she said.

Dr. Prescott has no financial disclosures

SAN DIEGO – A rounding team formed to oversee implementation of a bundle of ICU interventions reduced the incidence of ventilator-associated pneumonia (VAP) and the number of ventilation days, as well as the ICU and hospital length of stay, according to a new study conducted at a level 1 trauma center in California. The rounding team worked toward optimal implementation of the Society of Critical Care Medicine’s ABCDEF bundle, part of the society’s ICU liberation initiative.

ABCDEF stands for: Assessment, prevention, and management of pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; and Family engagement and empowerment.

The Community Regional Medical Center in Fresno, Calif., where the study was conducted, was chosen in 2015 to participate in the ICU liberation initiative. The facility serves a population of 3.2 million and sees just under 4,000 trauma patients per year.

After a 6-month retrospective analysis, the team members at the medical center realized they needed to improve ABCDEF implementation with respect to evaluating sedation practices and improving delirium assessment.

Before the start of the 17-month collaborative period, they formed an ICU liberation team called SMART, short for Sedation, Mobilization, Assessment Rounding Team, which included representatives from ICU nursing, pharmacy, respiratory therapy, physical therapy, physicians, and administration. They developed a daily rounding tool to help the team implement procedures, with the goal of reducing the continuous infusion of benzodiazepines and increasing intermittent dosing, the use of short-acting medications, and conducting spontaneous awakening and breathing trials. The SMART team made daily rounds to ensure that the ABCDEF bundle was being implemented.

The researchers then continued the analysis for another 12 months after the end of the initiative. During this last phase, the benefits of the SMART team became evident.

“Stick with it. Don’t let up. Don’t quit,” Wade Veneman, a respiratory therapist at the medical center, said in an interview. He presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “It can be particularly difficult in the face of critical care providers who may be skeptical of new initiatives. They think it’s something new, and they hope that it goes away. But this is something we feel we’re going to keep for a long time,” he added.

Jim Kling/MDedge News

Mr. Veneman hopes to implement the SMART program in the neurological critical care ICU. The medical director of that unit did not participate in the initial collaborative, but Mr. Veneman hopes to change that. “The data is going to show that his VAP and ventilator days are going up, and everywhere else they’re going down,” he said.

The researchers analyzed data on 1,127 mechanically ventilated patients in the ICU. At total of 197 patients were treated 6 months before the implementation of the collaborative, 519 during 17 months of collaborative implementation, and 411 in the 12 months after implementation. There were some differences between the populations: The before group was slightly younger than the after-implementation group (mean 41 vs. 44, P = .04), and the mean Injury Severity Score score was 24 in the before group, 22 during, and 20 after (P = .002). The researchers noted that the differences were clinically significant.

Benzodiazepine use declined, but the effect was statistically significant only in the after population. Continuous use declined from 87% before implementation to 83% during (P = .21) and 53% after (P less than .001). Intermittent use was 57% before implementation, increased to 61% during (P = .44), and fell to 44% after (P less than .001). Delirium assessment performance improved throughout, from 9% before implementation to 42% during (P less than .001) to 73% after implementation (P less than .001).

The VAP rate increased from 3.4% before the SMART program to 4.5% during implementation (P = .53), and then dropped to 0.9% afterward (P = .001). Ventilation days started at a mean of 10.5, then dropped to 9.5 during implementation (P = .30), and 8.2 after implementation (P = .027).

ICU length of stay improved from 10.7 before implementation to 9.3 afterward (P = .021), and overall hospital length of stay went from 17.3 days to 16.3 (P = .005).

The study was not funded. Mr. Veneman has no relevant financial disclosures.

SOURCE: Veneman W et al. CCC48, Abstract 63.

SAN DIEGO – A rounding team formed to oversee implementation of a bundle of ICU interventions reduced the incidence of ventilator-associated pneumonia (VAP) and the number of ventilation days, as well as the ICU and hospital length of stay, according to a new study conducted at a level 1 trauma center in California. The rounding team worked toward optimal implementation of the Society of Critical Care Medicine’s ABCDEF bundle, part of the society’s ICU liberation initiative.

ABCDEF stands for: Assessment, prevention, and management of pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; and Family engagement and empowerment.

The Community Regional Medical Center in Fresno, Calif., where the study was conducted, was chosen in 2015 to participate in the ICU liberation initiative. The facility serves a population of 3.2 million and sees just under 4,000 trauma patients per year.

After a 6-month retrospective analysis, the team members at the medical center realized they needed to improve ABCDEF implementation with respect to evaluating sedation practices and improving delirium assessment.

Before the start of the 17-month collaborative period, they formed an ICU liberation team called SMART, short for Sedation, Mobilization, Assessment Rounding Team, which included representatives from ICU nursing, pharmacy, respiratory therapy, physical therapy, physicians, and administration. They developed a daily rounding tool to help the team implement procedures, with the goal of reducing the continuous infusion of benzodiazepines and increasing intermittent dosing, the use of short-acting medications, and conducting spontaneous awakening and breathing trials. The SMART team made daily rounds to ensure that the ABCDEF bundle was being implemented.

The researchers then continued the analysis for another 12 months after the end of the initiative. During this last phase, the benefits of the SMART team became evident.

“Stick with it. Don’t let up. Don’t quit,” Wade Veneman, a respiratory therapist at the medical center, said in an interview. He presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “It can be particularly difficult in the face of critical care providers who may be skeptical of new initiatives. They think it’s something new, and they hope that it goes away. But this is something we feel we’re going to keep for a long time,” he added.

Jim Kling/MDedge News

Mr. Veneman hopes to implement the SMART program in the neurological critical care ICU. The medical director of that unit did not participate in the initial collaborative, but Mr. Veneman hopes to change that. “The data is going to show that his VAP and ventilator days are going up, and everywhere else they’re going down,” he said.

The researchers analyzed data on 1,127 mechanically ventilated patients in the ICU. At total of 197 patients were treated 6 months before the implementation of the collaborative, 519 during 17 months of collaborative implementation, and 411 in the 12 months after implementation. There were some differences between the populations: The before group was slightly younger than the after-implementation group (mean 41 vs. 44, P = .04), and the mean Injury Severity Score score was 24 in the before group, 22 during, and 20 after (P = .002). The researchers noted that the differences were clinically significant.

Benzodiazepine use declined, but the effect was statistically significant only in the after population. Continuous use declined from 87% before implementation to 83% during (P = .21) and 53% after (P less than .001). Intermittent use was 57% before implementation, increased to 61% during (P = .44), and fell to 44% after (P less than .001). Delirium assessment performance improved throughout, from 9% before implementation to 42% during (P less than .001) to 73% after implementation (P less than .001).

The VAP rate increased from 3.4% before the SMART program to 4.5% during implementation (P = .53), and then dropped to 0.9% afterward (P = .001). Ventilation days started at a mean of 10.5, then dropped to 9.5 during implementation (P = .30), and 8.2 after implementation (P = .027).

ICU length of stay improved from 10.7 before implementation to 9.3 afterward (P = .021), and overall hospital length of stay went from 17.3 days to 16.3 (P = .005).

The study was not funded. Mr. Veneman has no relevant financial disclosures.

SOURCE: Veneman W et al. CCC48, Abstract 63.

SAN DIEGO – A rounding team formed to oversee implementation of a bundle of ICU interventions reduced the incidence of ventilator-associated pneumonia (VAP) and the number of ventilation days, as well as the ICU and hospital length of stay, according to a new study conducted at a level 1 trauma center in California. The rounding team worked toward optimal implementation of the Society of Critical Care Medicine’s ABCDEF bundle, part of the society’s ICU liberation initiative.

ABCDEF stands for: Assessment, prevention, and management of pain; Both spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment, prevention, and management; Early mobility and exercise; and Family engagement and empowerment.

The Community Regional Medical Center in Fresno, Calif., where the study was conducted, was chosen in 2015 to participate in the ICU liberation initiative. The facility serves a population of 3.2 million and sees just under 4,000 trauma patients per year.

After a 6-month retrospective analysis, the team members at the medical center realized they needed to improve ABCDEF implementation with respect to evaluating sedation practices and improving delirium assessment.

Before the start of the 17-month collaborative period, they formed an ICU liberation team called SMART, short for Sedation, Mobilization, Assessment Rounding Team, which included representatives from ICU nursing, pharmacy, respiratory therapy, physical therapy, physicians, and administration. They developed a daily rounding tool to help the team implement procedures, with the goal of reducing the continuous infusion of benzodiazepines and increasing intermittent dosing, the use of short-acting medications, and conducting spontaneous awakening and breathing trials. The SMART team made daily rounds to ensure that the ABCDEF bundle was being implemented.

The researchers then continued the analysis for another 12 months after the end of the initiative. During this last phase, the benefits of the SMART team became evident.

“Stick with it. Don’t let up. Don’t quit,” Wade Veneman, a respiratory therapist at the medical center, said in an interview. He presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine. “It can be particularly difficult in the face of critical care providers who may be skeptical of new initiatives. They think it’s something new, and they hope that it goes away. But this is something we feel we’re going to keep for a long time,” he added.

Jim Kling/MDedge News

Mr. Veneman hopes to implement the SMART program in the neurological critical care ICU. The medical director of that unit did not participate in the initial collaborative, but Mr. Veneman hopes to change that. “The data is going to show that his VAP and ventilator days are going up, and everywhere else they’re going down,” he said.

The researchers analyzed data on 1,127 mechanically ventilated patients in the ICU. At total of 197 patients were treated 6 months before the implementation of the collaborative, 519 during 17 months of collaborative implementation, and 411 in the 12 months after implementation. There were some differences between the populations: The before group was slightly younger than the after-implementation group (mean 41 vs. 44, P = .04), and the mean Injury Severity Score score was 24 in the before group, 22 during, and 20 after (P = .002). The researchers noted that the differences were clinically significant.

Benzodiazepine use declined, but the effect was statistically significant only in the after population. Continuous use declined from 87% before implementation to 83% during (P = .21) and 53% after (P less than .001). Intermittent use was 57% before implementation, increased to 61% during (P = .44), and fell to 44% after (P less than .001). Delirium assessment performance improved throughout, from 9% before implementation to 42% during (P less than .001) to 73% after implementation (P less than .001).

The VAP rate increased from 3.4% before the SMART program to 4.5% during implementation (P = .53), and then dropped to 0.9% afterward (P = .001). Ventilation days started at a mean of 10.5, then dropped to 9.5 during implementation (P = .30), and 8.2 after implementation (P = .027).

ICU length of stay improved from 10.7 before implementation to 9.3 afterward (P = .021), and overall hospital length of stay went from 17.3 days to 16.3 (P = .005).

The study was not funded. Mr. Veneman has no relevant financial disclosures.

SOURCE: Veneman W et al. CCC48, Abstract 63.

SAN DIEGO – Powerful antibiotics come first to mind when hospitalized patients have sepsis, but a critical care pulmonology specialist urged colleagues to consider another treatment – heavy intravenous doses of vitamin C.

“There is evidence supporting benefit, and ample evidence supporting safety,” Michael H. Hooper, MD, who practices in Norfolk, Va., said in a pro-and-con debate over the use of vitamin C in sepsis at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Dr. Hooper’s debate opponent countered by noting the lack of quality research into vitamin C in sepsis and declared that its time has not yet come. “We need more data to know the safety of this drug,” said Andre Kalil, MD, professor of internal medicine and director of Transplant Infectious Diseases at the University of Nebraska Medical Center, Omaha.

Dr. Hooper was part of a member of a team led by Paul E. Marik, MD, FCCP, of Eastern Virginia Medical School, Norfolk, that made waves in 2017 with a study in Chest suggesting IV vitamin C has tremendous potential as a treatment for sepsis (Chest. 2017 Jun;151[6]:1229-38).

The retrospective study compared two groups of 47 patients with sepsis – a control group and a group that received treatment with intravenous vitamin C, hydrocortisone, and thiamine. Remarkably, the team found that 9% (4 of 47) of those in the treatment group died in the hospital, compared with 40% (19 of 47) in the control group (P less than .001).

The findings make sense, Dr. Hooper said, in light of the fact that “our patients are remarkably deficient” in vitamin C. He pointed to a 2017 study that found nearly 40% of 24 patients with septic shock were deficient in vitamin C – despite getting recommended enteral nutrition, parenteral nutrition or both – compared with 25% of patients who were not septic. The study authors believe the difference is probably due to “increased metabolism due to the enhanced inflammatory response observed in septic shock” (Crit Care. 2017 Dec 11;21[1]:300).

“We’re dealing with a population of patients who need some sort of repletion of this vitamin,” Dr. Hooper said.

Why not try oral administration of vitamin C? “Oral administration at regular doses doesn’t work,” he said. “If you have normal volunteers who are made deficient, then you administer the recommended allowance, it takes days or weeks to return levels to normal.”

Dr. Hooper added that the goal of vitamin C therapy isn’t simply to restore proper levels in plasma. In addition, he said, “we’re trying to restore levels in crucial organs.”

He said the cost of treatment with IV vitamin C is low, and no serious adverse events have been seen in studies of the vitamin’s use in critical care.

In his comments at the debate, Dr. Kalil pointed to several weaknesses in the 2017 study of vitamin C in sepsis. According to him, it had many problems, including a sample size that lacked statistical power and imbalances in the two groups. He raised concerns about the study in a 2017 letter published in Chest titled “Vitamin C Is Not Ready for Prime Time in Sepsis but a Solution Is Close,” noting that the control group was sicker and none of those patients had their vitamin C levels measured (Chest. 2017 Sep;152[3]:676).

Randy Dotinga/MDedge News

He added that “acute renal failure is associated with high doses of vitamin C.”

As of July 2018, several clinical trials into vitamin C, hydrocortisone, and thiamine for the treatment of septic shock were underway or planned, according to a report that described the current randomized, placebo-controlled, multicenter Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial in the United States. The report notes that “robust evidence” for this approach is lacking, although “the potential effectiveness of this medication combination is rooted in biologic plausibility and supported by small clinical trials of the various individual components.” (Crit Care. 2018;22:283)

Dr. Hooper is an executive committee member and principal investigator with the Vitamin C, Thiamine And Steroids in Sepsis (VICTAS) study. Dr. Kalil reports no relevant disclosures.

SAN DIEGO – Powerful antibiotics come first to mind when hospitalized patients have sepsis, but a critical care pulmonology specialist urged colleagues to consider another treatment – heavy intravenous doses of vitamin C.

“There is evidence supporting benefit, and ample evidence supporting safety,” Michael H. Hooper, MD, who practices in Norfolk, Va., said in a pro-and-con debate over the use of vitamin C in sepsis at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Dr. Hooper’s debate opponent countered by noting the lack of quality research into vitamin C in sepsis and declared that its time has not yet come. “We need more data to know the safety of this drug,” said Andre Kalil, MD, professor of internal medicine and director of Transplant Infectious Diseases at the University of Nebraska Medical Center, Omaha.

Dr. Hooper was part of a member of a team led by Paul E. Marik, MD, FCCP, of Eastern Virginia Medical School, Norfolk, that made waves in 2017 with a study in Chest suggesting IV vitamin C has tremendous potential as a treatment for sepsis (Chest. 2017 Jun;151[6]:1229-38).

The retrospective study compared two groups of 47 patients with sepsis – a control group and a group that received treatment with intravenous vitamin C, hydrocortisone, and thiamine. Remarkably, the team found that 9% (4 of 47) of those in the treatment group died in the hospital, compared with 40% (19 of 47) in the control group (P less than .001).

The findings make sense, Dr. Hooper said, in light of the fact that “our patients are remarkably deficient” in vitamin C. He pointed to a 2017 study that found nearly 40% of 24 patients with septic shock were deficient in vitamin C – despite getting recommended enteral nutrition, parenteral nutrition or both – compared with 25% of patients who were not septic. The study authors believe the difference is probably due to “increased metabolism due to the enhanced inflammatory response observed in septic shock” (Crit Care. 2017 Dec 11;21[1]:300).

“We’re dealing with a population of patients who need some sort of repletion of this vitamin,” Dr. Hooper said.

Why not try oral administration of vitamin C? “Oral administration at regular doses doesn’t work,” he said. “If you have normal volunteers who are made deficient, then you administer the recommended allowance, it takes days or weeks to return levels to normal.”

Dr. Hooper added that the goal of vitamin C therapy isn’t simply to restore proper levels in plasma. In addition, he said, “we’re trying to restore levels in crucial organs.”

He said the cost of treatment with IV vitamin C is low, and no serious adverse events have been seen in studies of the vitamin’s use in critical care.

In his comments at the debate, Dr. Kalil pointed to several weaknesses in the 2017 study of vitamin C in sepsis. According to him, it had many problems, including a sample size that lacked statistical power and imbalances in the two groups. He raised concerns about the study in a 2017 letter published in Chest titled “Vitamin C Is Not Ready for Prime Time in Sepsis but a Solution Is Close,” noting that the control group was sicker and none of those patients had their vitamin C levels measured (Chest. 2017 Sep;152[3]:676).

Randy Dotinga/MDedge News

He added that “acute renal failure is associated with high doses of vitamin C.”

As of July 2018, several clinical trials into vitamin C, hydrocortisone, and thiamine for the treatment of septic shock were underway or planned, according to a report that described the current randomized, placebo-controlled, multicenter Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial in the United States. The report notes that “robust evidence” for this approach is lacking, although “the potential effectiveness of this medication combination is rooted in biologic plausibility and supported by small clinical trials of the various individual components.” (Crit Care. 2018;22:283)

Dr. Hooper is an executive committee member and principal investigator with the Vitamin C, Thiamine And Steroids in Sepsis (VICTAS) study. Dr. Kalil reports no relevant disclosures.

SAN DIEGO – Powerful antibiotics come first to mind when hospitalized patients have sepsis, but a critical care pulmonology specialist urged colleagues to consider another treatment – heavy intravenous doses of vitamin C.

“There is evidence supporting benefit, and ample evidence supporting safety,” Michael H. Hooper, MD, who practices in Norfolk, Va., said in a pro-and-con debate over the use of vitamin C in sepsis at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Dr. Hooper’s debate opponent countered by noting the lack of quality research into vitamin C in sepsis and declared that its time has not yet come. “We need more data to know the safety of this drug,” said Andre Kalil, MD, professor of internal medicine and director of Transplant Infectious Diseases at the University of Nebraska Medical Center, Omaha.

Dr. Hooper was part of a member of a team led by Paul E. Marik, MD, FCCP, of Eastern Virginia Medical School, Norfolk, that made waves in 2017 with a study in Chest suggesting IV vitamin C has tremendous potential as a treatment for sepsis (Chest. 2017 Jun;151[6]:1229-38).

The retrospective study compared two groups of 47 patients with sepsis – a control group and a group that received treatment with intravenous vitamin C, hydrocortisone, and thiamine. Remarkably, the team found that 9% (4 of 47) of those in the treatment group died in the hospital, compared with 40% (19 of 47) in the control group (P less than .001).

The findings make sense, Dr. Hooper said, in light of the fact that “our patients are remarkably deficient” in vitamin C. He pointed to a 2017 study that found nearly 40% of 24 patients with septic shock were deficient in vitamin C – despite getting recommended enteral nutrition, parenteral nutrition or both – compared with 25% of patients who were not septic. The study authors believe the difference is probably due to “increased metabolism due to the enhanced inflammatory response observed in septic shock” (Crit Care. 2017 Dec 11;21[1]:300).

“We’re dealing with a population of patients who need some sort of repletion of this vitamin,” Dr. Hooper said.

Why not try oral administration of vitamin C? “Oral administration at regular doses doesn’t work,” he said. “If you have normal volunteers who are made deficient, then you administer the recommended allowance, it takes days or weeks to return levels to normal.”

Dr. Hooper added that the goal of vitamin C therapy isn’t simply to restore proper levels in plasma. In addition, he said, “we’re trying to restore levels in crucial organs.”

He said the cost of treatment with IV vitamin C is low, and no serious adverse events have been seen in studies of the vitamin’s use in critical care.

In his comments at the debate, Dr. Kalil pointed to several weaknesses in the 2017 study of vitamin C in sepsis. According to him, it had many problems, including a sample size that lacked statistical power and imbalances in the two groups. He raised concerns about the study in a 2017 letter published in Chest titled “Vitamin C Is Not Ready for Prime Time in Sepsis but a Solution Is Close,” noting that the control group was sicker and none of those patients had their vitamin C levels measured (Chest. 2017 Sep;152[3]:676).

Randy Dotinga/MDedge News

He added that “acute renal failure is associated with high doses of vitamin C.”

As of July 2018, several clinical trials into vitamin C, hydrocortisone, and thiamine for the treatment of septic shock were underway or planned, according to a report that described the current randomized, placebo-controlled, multicenter Ascorbic Acid, Corticosteroids, and Thiamine in Sepsis (ACTS) trial in the United States. The report notes that “robust evidence” for this approach is lacking, although “the potential effectiveness of this medication combination is rooted in biologic plausibility and supported by small clinical trials of the various individual components.” (Crit Care. 2018;22:283)

Dr. Hooper is an executive committee member and principal investigator with the Vitamin C, Thiamine And Steroids in Sepsis (VICTAS) study. Dr. Kalil reports no relevant disclosures.

SAN DIEGO – In the pediatric intensive care unit (PICU), rapid whole genome sequencing (rWGS) with targeted phenotype analysis often leads to specific changes in patient management, similar to what is seen when rWGS is applied to neonatal ICUs. The findings come from the first study to look at outcomes of rWGS in the PICU outside of infancy.

NaiyanaDonraman/Thinkstock

In the NICU, previous studies have shown an rWGS diagnostic rate ranging from 36% to 57%, and an estimated 49%-72% of these diagnoses result in changes to patient management; 38%-45% of those diagnoses had not been previously considered.

The researchers found similar benefits when the age of patients was extended to 18 years in the PICU. “We were happy to see we were able to make specific changes in ICU management, with three of those being medication changes based on the diagnosis, and one being in the transition to palliative care while the patient was still in the PICU,” Erica Sanford, MD, said in an interview.

Dr. Sanford is a pediatric clinical care fellow at the University of California, San Diego. She presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Changes as a result of rWGS included factor replacement for a factor XIII deficiency, avoidance of renal biopsy because the diagnosis was made genetically, and use of serial MRI and other imaging methods to identify disorder-related sequela. “We’re hopeful as the turnaround for genome sequencing decreases that we’ll be able to offer this as a test when appropriate when a patient is presenting with an illness that doesn’t have a clear etiologic diagnosis,” said Dr. Sanford.

Certainly not every patient in the PICU should undergo rWGS, given its expense. Although the study was too small to identify candidate patients, there were some trends – patients in cardiac arrest were more likely to be receiving a genetic diagnosis. “We weren’t able to answer the question of which patients in the pediatric ICU should get whole genome sequencing – our next step is to have a larger group of patients so we can determine specifically which patients might benefit,” said Dr. Sanford. The team also plans to do a cost analysis of rWGS in the PICU setting.

The researchers examined data from a PICU at a tertiary children’s hospital, including records from 38 patients who underwent rWGS between July 2016 and May 2018. Based on the initial sequencing results, 18 underwent diagnostic rWGS. The average age of children was 5.7 years (median 3 years), with patients ranging from 4 months to 18 years old.

The most common reasons for PICU admission were shock (16% of all patients, 17% of patients who received diagnostic rWGS), respiratory failure (18% and 17%), cardiac arrest (13% and 22%), and altered mental status (13% and 11%).

Eleven of 18 patients (61%) who received an rWGS diagnosis experienced a subacute, non-ICU change in management. Four diagnoses (22%) led to a change in ICU management, and three led to no changes in patient management.

The National Institutes of Health funded the study. Dr. Sanford had no relevant financial disclosures.

SOURCE: Sanford E et al. CCC48, Abstract 373.

SAN DIEGO – In the pediatric intensive care unit (PICU), rapid whole genome sequencing (rWGS) with targeted phenotype analysis often leads to specific changes in patient management, similar to what is seen when rWGS is applied to neonatal ICUs. The findings come from the first study to look at outcomes of rWGS in the PICU outside of infancy.

NaiyanaDonraman/Thinkstock

In the NICU, previous studies have shown an rWGS diagnostic rate ranging from 36% to 57%, and an estimated 49%-72% of these diagnoses result in changes to patient management; 38%-45% of those diagnoses had not been previously considered.

The researchers found similar benefits when the age of patients was extended to 18 years in the PICU. “We were happy to see we were able to make specific changes in ICU management, with three of those being medication changes based on the diagnosis, and one being in the transition to palliative care while the patient was still in the PICU,” Erica Sanford, MD, said in an interview.

Dr. Sanford is a pediatric clinical care fellow at the University of California, San Diego. She presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Changes as a result of rWGS included factor replacement for a factor XIII deficiency, avoidance of renal biopsy because the diagnosis was made genetically, and use of serial MRI and other imaging methods to identify disorder-related sequela. “We’re hopeful as the turnaround for genome sequencing decreases that we’ll be able to offer this as a test when appropriate when a patient is presenting with an illness that doesn’t have a clear etiologic diagnosis,” said Dr. Sanford.

Certainly not every patient in the PICU should undergo rWGS, given its expense. Although the study was too small to identify candidate patients, there were some trends – patients in cardiac arrest were more likely to be receiving a genetic diagnosis. “We weren’t able to answer the question of which patients in the pediatric ICU should get whole genome sequencing – our next step is to have a larger group of patients so we can determine specifically which patients might benefit,” said Dr. Sanford. The team also plans to do a cost analysis of rWGS in the PICU setting.

The researchers examined data from a PICU at a tertiary children’s hospital, including records from 38 patients who underwent rWGS between July 2016 and May 2018. Based on the initial sequencing results, 18 underwent diagnostic rWGS. The average age of children was 5.7 years (median 3 years), with patients ranging from 4 months to 18 years old.

The most common reasons for PICU admission were shock (16% of all patients, 17% of patients who received diagnostic rWGS), respiratory failure (18% and 17%), cardiac arrest (13% and 22%), and altered mental status (13% and 11%).

Eleven of 18 patients (61%) who received an rWGS diagnosis experienced a subacute, non-ICU change in management. Four diagnoses (22%) led to a change in ICU management, and three led to no changes in patient management.

The National Institutes of Health funded the study. Dr. Sanford had no relevant financial disclosures.

SOURCE: Sanford E et al. CCC48, Abstract 373.

SAN DIEGO – In the pediatric intensive care unit (PICU), rapid whole genome sequencing (rWGS) with targeted phenotype analysis often leads to specific changes in patient management, similar to what is seen when rWGS is applied to neonatal ICUs. The findings come from the first study to look at outcomes of rWGS in the PICU outside of infancy.

NaiyanaDonraman/Thinkstock

In the NICU, previous studies have shown an rWGS diagnostic rate ranging from 36% to 57%, and an estimated 49%-72% of these diagnoses result in changes to patient management; 38%-45% of those diagnoses had not been previously considered.

The researchers found similar benefits when the age of patients was extended to 18 years in the PICU. “We were happy to see we were able to make specific changes in ICU management, with three of those being medication changes based on the diagnosis, and one being in the transition to palliative care while the patient was still in the PICU,” Erica Sanford, MD, said in an interview.

Dr. Sanford is a pediatric clinical care fellow at the University of California, San Diego. She presented the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

Changes as a result of rWGS included factor replacement for a factor XIII deficiency, avoidance of renal biopsy because the diagnosis was made genetically, and use of serial MRI and other imaging methods to identify disorder-related sequela. “We’re hopeful as the turnaround for genome sequencing decreases that we’ll be able to offer this as a test when appropriate when a patient is presenting with an illness that doesn’t have a clear etiologic diagnosis,” said Dr. Sanford.

Certainly not every patient in the PICU should undergo rWGS, given its expense. Although the study was too small to identify candidate patients, there were some trends – patients in cardiac arrest were more likely to be receiving a genetic diagnosis. “We weren’t able to answer the question of which patients in the pediatric ICU should get whole genome sequencing – our next step is to have a larger group of patients so we can determine specifically which patients might benefit,” said Dr. Sanford. The team also plans to do a cost analysis of rWGS in the PICU setting.

The researchers examined data from a PICU at a tertiary children’s hospital, including records from 38 patients who underwent rWGS between July 2016 and May 2018. Based on the initial sequencing results, 18 underwent diagnostic rWGS. The average age of children was 5.7 years (median 3 years), with patients ranging from 4 months to 18 years old.

The most common reasons for PICU admission were shock (16% of all patients, 17% of patients who received diagnostic rWGS), respiratory failure (18% and 17%), cardiac arrest (13% and 22%), and altered mental status (13% and 11%).

Eleven of 18 patients (61%) who received an rWGS diagnosis experienced a subacute, non-ICU change in management. Four diagnoses (22%) led to a change in ICU management, and three led to no changes in patient management.

The National Institutes of Health funded the study. Dr. Sanford had no relevant financial disclosures.

SOURCE: Sanford E et al. CCC48, Abstract 373.

SAN DIEGO – Does rudeness from a colleague prevent physicians from noticing a diagnostic error and challenging it? A new study suggests it might not, at least in the context of hand-offs from dismissive and insulting fellow doctors.

Instead, a simulation found that experience seems to be the key factor in giving physicians the guts – or the awareness – to change course. Still, the findings hint that rudeness may still have a negative effect on one group – resident physicians.

“It appears that we are building resilience somewhere in training,” said study lead author Michael Avesar, MD, a pediatric critical care medicine fellow at Children’s Hospital Los Angeles.

Dr. Avesar spoke in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The initial motivation of the study wasn’t to gain more understanding of rudeness in medicine. Instead, Dr. Avesar said, “We started off with trying to find ways to understand how physicians think during high-stakes decisions in stressful or time-limited situations. We wanted to see if people were able to challenge the momentum of diagnostic error. That’s when we learned more about the rudeness literature.”

Yes, it’s true: Researchers have devoted time to studying rudeness in medicine. After all, it’s quite common. A 2017 Israeli study in Pediatrics declared it’s “routinely experienced by medical teams.” That study, also based on simulations, determined that “rudeness has robust, deleterious effects on the performance of medical teams. Moreover, exposure to rudeness debilitated the very collaborative mechanisms recognized as essential for patient care and safety” (Pediatrics. 2017 Feb. doi: 10.1542/peds.2016-2305).

For the new study, Dr. Avesar and his colleagues ultimately decided to explore possible links between rudeness and diagnostic error. To explore the issue, they created a simulation of a hand-off of a pediatric patient from the operating team to the ICU.

In the simulation, the “physician” handing off the “patient” incorrectly noted a diagnosis of sepsis. In fact, the patient had cardiac tamponade.

The physician, played by an actor, was instructed to either act in a neutral fashion during the hand-off or be rude. But rudeness, it turns out, isn’t easy to define, even if we all think we know it when we see it.

“There’s a lot of debate as to what is ‘rude,’ ” Dr. Avesar said. The researchers settled on a level of rudeness that wasn’t “too mean” but was still inappropriate: It featured frequent interruptions during the hand-off, lack of eye contact, and abrupt departures. In some simulations, the actor insulted the colleagues of the recipient of the hand-off.

In other words, Dr. Avesar said, the actor was a jerk.

The researchers tested the “neutral” and “rude” hand-off scenarios in 41 simulations. The physicians who played the recipients of the hand-offs included 11 attendings, 14 fellows, and 16 residents.

Eighty-two percent of the attendings (9/11) challenged the diagnosis, as did 86% (12/14) of the fellows. Only 31% (5/16) of residents challenged the diagnosis; this difference from the other groups was statistically significant.

Half of the eight residents exposed to a “neutral” handoff challenged the correct diagnosis, while only 13% (1/8) of those who were treated rudely did. “While the P value was not significant, previous literature focused on residents supports this trend,” Dr. Avesar said.

It’s possible that certain residents gain the knowledge and experience to overcome rudeness over time, he said. That, he said, leads to an intriguing question: “Could we find out how resilience is learned and how to replicate it?”

Moving forward, he said, the team will try to figure out whether there’s a link between personality types and reactions to rudeness.

Eventually, he said, the team may test ways to reduce the effects of rudeness and boost critical thinking. “We see this as a long-term strategy to enhance medical education and patient safety,” he said.

No study funding is reported. Dr. Avesar reports no relevant disclosures.

SOURCE: Avesar M et al. Crit Care Med. 2019 Jan;47(1):682, Abstract 1412.

SAN DIEGO – Does rudeness from a colleague prevent physicians from noticing a diagnostic error and challenging it? A new study suggests it might not, at least in the context of hand-offs from dismissive and insulting fellow doctors.

Instead, a simulation found that experience seems to be the key factor in giving physicians the guts – or the awareness – to change course. Still, the findings hint that rudeness may still have a negative effect on one group – resident physicians.

“It appears that we are building resilience somewhere in training,” said study lead author Michael Avesar, MD, a pediatric critical care medicine fellow at Children’s Hospital Los Angeles.

Dr. Avesar spoke in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The initial motivation of the study wasn’t to gain more understanding of rudeness in medicine. Instead, Dr. Avesar said, “We started off with trying to find ways to understand how physicians think during high-stakes decisions in stressful or time-limited situations. We wanted to see if people were able to challenge the momentum of diagnostic error. That’s when we learned more about the rudeness literature.”

Yes, it’s true: Researchers have devoted time to studying rudeness in medicine. After all, it’s quite common. A 2017 Israeli study in Pediatrics declared it’s “routinely experienced by medical teams.” That study, also based on simulations, determined that “rudeness has robust, deleterious effects on the performance of medical teams. Moreover, exposure to rudeness debilitated the very collaborative mechanisms recognized as essential for patient care and safety” (Pediatrics. 2017 Feb. doi: 10.1542/peds.2016-2305).

For the new study, Dr. Avesar and his colleagues ultimately decided to explore possible links between rudeness and diagnostic error. To explore the issue, they created a simulation of a hand-off of a pediatric patient from the operating team to the ICU.

In the simulation, the “physician” handing off the “patient” incorrectly noted a diagnosis of sepsis. In fact, the patient had cardiac tamponade.

The physician, played by an actor, was instructed to either act in a neutral fashion during the hand-off or be rude. But rudeness, it turns out, isn’t easy to define, even if we all think we know it when we see it.

“There’s a lot of debate as to what is ‘rude,’ ” Dr. Avesar said. The researchers settled on a level of rudeness that wasn’t “too mean” but was still inappropriate: It featured frequent interruptions during the hand-off, lack of eye contact, and abrupt departures. In some simulations, the actor insulted the colleagues of the recipient of the hand-off.

In other words, Dr. Avesar said, the actor was a jerk.

The researchers tested the “neutral” and “rude” hand-off scenarios in 41 simulations. The physicians who played the recipients of the hand-offs included 11 attendings, 14 fellows, and 16 residents.

Eighty-two percent of the attendings (9/11) challenged the diagnosis, as did 86% (12/14) of the fellows. Only 31% (5/16) of residents challenged the diagnosis; this difference from the other groups was statistically significant.

Half of the eight residents exposed to a “neutral” handoff challenged the correct diagnosis, while only 13% (1/8) of those who were treated rudely did. “While the P value was not significant, previous literature focused on residents supports this trend,” Dr. Avesar said.

It’s possible that certain residents gain the knowledge and experience to overcome rudeness over time, he said. That, he said, leads to an intriguing question: “Could we find out how resilience is learned and how to replicate it?”

Moving forward, he said, the team will try to figure out whether there’s a link between personality types and reactions to rudeness.

Eventually, he said, the team may test ways to reduce the effects of rudeness and boost critical thinking. “We see this as a long-term strategy to enhance medical education and patient safety,” he said.

No study funding is reported. Dr. Avesar reports no relevant disclosures.

SOURCE: Avesar M et al. Crit Care Med. 2019 Jan;47(1):682, Abstract 1412.

SAN DIEGO – Does rudeness from a colleague prevent physicians from noticing a diagnostic error and challenging it? A new study suggests it might not, at least in the context of hand-offs from dismissive and insulting fellow doctors.

Instead, a simulation found that experience seems to be the key factor in giving physicians the guts – or the awareness – to change course. Still, the findings hint that rudeness may still have a negative effect on one group – resident physicians.

“It appears that we are building resilience somewhere in training,” said study lead author Michael Avesar, MD, a pediatric critical care medicine fellow at Children’s Hospital Los Angeles.

Dr. Avesar spoke in an interview following the presentation of the study findings at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

The initial motivation of the study wasn’t to gain more understanding of rudeness in medicine. Instead, Dr. Avesar said, “We started off with trying to find ways to understand how physicians think during high-stakes decisions in stressful or time-limited situations. We wanted to see if people were able to challenge the momentum of diagnostic error. That’s when we learned more about the rudeness literature.”

Yes, it’s true: Researchers have devoted time to studying rudeness in medicine. After all, it’s quite common. A 2017 Israeli study in Pediatrics declared it’s “routinely experienced by medical teams.” That study, also based on simulations, determined that “rudeness has robust, deleterious effects on the performance of medical teams. Moreover, exposure to rudeness debilitated the very collaborative mechanisms recognized as essential for patient care and safety” (Pediatrics. 2017 Feb. doi: 10.1542/peds.2016-2305).

For the new study, Dr. Avesar and his colleagues ultimately decided to explore possible links between rudeness and diagnostic error. To explore the issue, they created a simulation of a hand-off of a pediatric patient from the operating team to the ICU.

In the simulation, the “physician” handing off the “patient” incorrectly noted a diagnosis of sepsis. In fact, the patient had cardiac tamponade.

The physician, played by an actor, was instructed to either act in a neutral fashion during the hand-off or be rude. But rudeness, it turns out, isn’t easy to define, even if we all think we know it when we see it.

“There’s a lot of debate as to what is ‘rude,’ ” Dr. Avesar said. The researchers settled on a level of rudeness that wasn’t “too mean” but was still inappropriate: It featured frequent interruptions during the hand-off, lack of eye contact, and abrupt departures. In some simulations, the actor insulted the colleagues of the recipient of the hand-off.

In other words, Dr. Avesar said, the actor was a jerk.

The researchers tested the “neutral” and “rude” hand-off scenarios in 41 simulations. The physicians who played the recipients of the hand-offs included 11 attendings, 14 fellows, and 16 residents.

Eighty-two percent of the attendings (9/11) challenged the diagnosis, as did 86% (12/14) of the fellows. Only 31% (5/16) of residents challenged the diagnosis; this difference from the other groups was statistically significant.

Half of the eight residents exposed to a “neutral” handoff challenged the correct diagnosis, while only 13% (1/8) of those who were treated rudely did. “While the P value was not significant, previous literature focused on residents supports this trend,” Dr. Avesar said.

It’s possible that certain residents gain the knowledge and experience to overcome rudeness over time, he said. That, he said, leads to an intriguing question: “Could we find out how resilience is learned and how to replicate it?”

Moving forward, he said, the team will try to figure out whether there’s a link between personality types and reactions to rudeness.

Eventually, he said, the team may test ways to reduce the effects of rudeness and boost critical thinking. “We see this as a long-term strategy to enhance medical education and patient safety,” he said.

No study funding is reported. Dr. Avesar reports no relevant disclosures.

SOURCE: Avesar M et al. Crit Care Med. 2019 Jan;47(1):682, Abstract 1412.

SAN DIEGO – Severely injured patients often experience a massive inflammatory and immunomodulatory response that can lead to multiple organ failure, nosocomial infections, long ICU stays, and poor outcomes. But not all of them do. Some patients recover relatively rapidly, achieve earlier release, and have a faster immunologic recovery trajectory.

The longstanding theory, according to Ronald Maier, MD, a professor of surgery at the University of Washington, is that a trauma-related stimulus leads to an aggressive inflammatory response that can lead to multiple organ failure and death. In patients who recover from this early challenge, the theory goes, a counterregulatory response may overexuberantly down-regulate the inflammatory storm, which leaves the patient vulnerable to infections and poor wound healing. Then a later infection, sepsis, endotoxemia, or some other stimulus may ramp up the inflammatory system again, which leads to a crisis that can trigger mortality well after the initial trauma. Patients who recover from this challenge then return to homeostasis.

It’s a neat theory, but it’s wrong, said Dr. Maier in a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine. It has been undercut by genomic technology and high-throughput methods that have provided a new approach to investigating the underlying biology, as well as the ability to test circulating white blood cells to measure a patient’s immune response to traumatic injury.

“If you look at the underlying biology by looking at the genomic response, you can see that it’s not a sequential process. There is simultaneous up-regulation and down-regulation,” said Dr. Maier.

A study of 35 trauma patients using a gene chip found a measurable change in expression of over 17,000 genes; 5,136 genes had at least a twofold change in expression. “Eighty percent of the human genome changes measurably when you are hit by a cement truck,” said Dr. Maier.

To researchers’ surprise, more genes were found to be down-regulated in the immediate aftermath of the injury, and most of those down-regulated genes are involved in adaptive immunity. Up-regulated pathways were included in the innate and proinflammatory response. “The simultaneous down-regulation of the adaptive arm explains why the patients in the ICU with severe injuries are very susceptible to nosocomial infections, poor wound healing, and multiple complications,” said Dr. Maier.

Genomic studies also show down-regulation of genes associated with phagocytosis even out to 45 days. “Sometimes I wonder why every patient doesn’t evolve a nosocomial infection as a consequence of this impact on the immune system. In fact, I think it’s a great testimony to the countermeasures we’ve taken as far as sterility, hand washing – we’ve been able to prevent this dysfunction from being expressed as a nosocomial infection,” said Dr. Maier.

The genomic analysis can also be used to discriminate patients who regain homeostasis relatively quickly after severe trauma. There seems to be an inflection point between patients who resolve by 5 days and those who go on to experience prolonged ICU stays.

Perhaps surprisingly, the researchers found little difference between the two groups in terms of specific genes that were up- or down-regulated. Instead, the “uncomplicated” group saw their altered gene expression patterns return more quickly to baseline levels, whereas “complicated” patients lingered in the dysregulated state. “We’ve been chasing biomarkers for 35 years, and this explains why it’s very difficult. Those who do well return toward normal quickly. Those who have complications stay abnormal,” said Dr. Maier.

Instead, researchers identified a panel of 63 gene probes that can track the overall progress of the “genomic storm,” as he referred to the changes that occur in the wake of trauma. “This panel of 63 genes is the best predictor of the patient’s response to injury – better than injury severity score, better than multiple organ failure scores,” he said.

Dr. Maier is confident that such panels can alter patient management, even outside of trauma. “It may allow us to show which patients are going to have risk of early recurrence because of alterations in their adaptive immunity versus those who aren’t. We’re also going to predict those who are going to have infectious complications. Hopefully we’ll soon have a handle on which patients we need to be most aggressive with, and we can use monitoring to measure our therapeutic impact,” said Dr. Maier.
 

email address

SOURCE: Add the first author et al., journal citation/abstract number, and hyperlink it here.

SAN DIEGO – Severely injured patients often experience a massive inflammatory and immunomodulatory response that can lead to multiple organ failure, nosocomial infections, long ICU stays, and poor outcomes. But not all of them do. Some patients recover relatively rapidly, achieve earlier release, and have a faster immunologic recovery trajectory.

The longstanding theory, according to Ronald Maier, MD, a professor of surgery at the University of Washington, is that a trauma-related stimulus leads to an aggressive inflammatory response that can lead to multiple organ failure and death. In patients who recover from this early challenge, the theory goes, a counterregulatory response may overexuberantly down-regulate the inflammatory storm, which leaves the patient vulnerable to infections and poor wound healing. Then a later infection, sepsis, endotoxemia, or some other stimulus may ramp up the inflammatory system again, which leads to a crisis that can trigger mortality well after the initial trauma. Patients who recover from this challenge then return to homeostasis.

It’s a neat theory, but it’s wrong, said Dr. Maier in a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine. It has been undercut by genomic technology and high-throughput methods that have provided a new approach to investigating the underlying biology, as well as the ability to test circulating white blood cells to measure a patient’s immune response to traumatic injury.

“If you look at the underlying biology by looking at the genomic response, you can see that it’s not a sequential process. There is simultaneous up-regulation and down-regulation,” said Dr. Maier.

A study of 35 trauma patients using a gene chip found a measurable change in expression of over 17,000 genes; 5,136 genes had at least a twofold change in expression. “Eighty percent of the human genome changes measurably when you are hit by a cement truck,” said Dr. Maier.

To researchers’ surprise, more genes were found to be down-regulated in the immediate aftermath of the injury, and most of those down-regulated genes are involved in adaptive immunity. Up-regulated pathways were included in the innate and proinflammatory response. “The simultaneous down-regulation of the adaptive arm explains why the patients in the ICU with severe injuries are very susceptible to nosocomial infections, poor wound healing, and multiple complications,” said Dr. Maier.

Genomic studies also show down-regulation of genes associated with phagocytosis even out to 45 days. “Sometimes I wonder why every patient doesn’t evolve a nosocomial infection as a consequence of this impact on the immune system. In fact, I think it’s a great testimony to the countermeasures we’ve taken as far as sterility, hand washing – we’ve been able to prevent this dysfunction from being expressed as a nosocomial infection,” said Dr. Maier.

The genomic analysis can also be used to discriminate patients who regain homeostasis relatively quickly after severe trauma. There seems to be an inflection point between patients who resolve by 5 days and those who go on to experience prolonged ICU stays.

Perhaps surprisingly, the researchers found little difference between the two groups in terms of specific genes that were up- or down-regulated. Instead, the “uncomplicated” group saw their altered gene expression patterns return more quickly to baseline levels, whereas “complicated” patients lingered in the dysregulated state. “We’ve been chasing biomarkers for 35 years, and this explains why it’s very difficult. Those who do well return toward normal quickly. Those who have complications stay abnormal,” said Dr. Maier.

Instead, researchers identified a panel of 63 gene probes that can track the overall progress of the “genomic storm,” as he referred to the changes that occur in the wake of trauma. “This panel of 63 genes is the best predictor of the patient’s response to injury – better than injury severity score, better than multiple organ failure scores,” he said.

Dr. Maier is confident that such panels can alter patient management, even outside of trauma. “It may allow us to show which patients are going to have risk of early recurrence because of alterations in their adaptive immunity versus those who aren’t. We’re also going to predict those who are going to have infectious complications. Hopefully we’ll soon have a handle on which patients we need to be most aggressive with, and we can use monitoring to measure our therapeutic impact,” said Dr. Maier.
 

email address

SOURCE: Add the first author et al., journal citation/abstract number, and hyperlink it here.

SAN DIEGO – Severely injured patients often experience a massive inflammatory and immunomodulatory response that can lead to multiple organ failure, nosocomial infections, long ICU stays, and poor outcomes. But not all of them do. Some patients recover relatively rapidly, achieve earlier release, and have a faster immunologic recovery trajectory.

The longstanding theory, according to Ronald Maier, MD, a professor of surgery at the University of Washington, is that a trauma-related stimulus leads to an aggressive inflammatory response that can lead to multiple organ failure and death. In patients who recover from this early challenge, the theory goes, a counterregulatory response may overexuberantly down-regulate the inflammatory storm, which leaves the patient vulnerable to infections and poor wound healing. Then a later infection, sepsis, endotoxemia, or some other stimulus may ramp up the inflammatory system again, which leads to a crisis that can trigger mortality well after the initial trauma. Patients who recover from this challenge then return to homeostasis.

It’s a neat theory, but it’s wrong, said Dr. Maier in a talk at the Critical Care Congress sponsored by the Society of Critical Care Medicine. It has been undercut by genomic technology and high-throughput methods that have provided a new approach to investigating the underlying biology, as well as the ability to test circulating white blood cells to measure a patient’s immune response to traumatic injury.

“If you look at the underlying biology by looking at the genomic response, you can see that it’s not a sequential process. There is simultaneous up-regulation and down-regulation,” said Dr. Maier.

A study of 35 trauma patients using a gene chip found a measurable change in expression of over 17,000 genes; 5,136 genes had at least a twofold change in expression. “Eighty percent of the human genome changes measurably when you are hit by a cement truck,” said Dr. Maier.

To researchers’ surprise, more genes were found to be down-regulated in the immediate aftermath of the injury, and most of those down-regulated genes are involved in adaptive immunity. Up-regulated pathways were included in the innate and proinflammatory response. “The simultaneous down-regulation of the adaptive arm explains why the patients in the ICU with severe injuries are very susceptible to nosocomial infections, poor wound healing, and multiple complications,” said Dr. Maier.

Genomic studies also show down-regulation of genes associated with phagocytosis even out to 45 days. “Sometimes I wonder why every patient doesn’t evolve a nosocomial infection as a consequence of this impact on the immune system. In fact, I think it’s a great testimony to the countermeasures we’ve taken as far as sterility, hand washing – we’ve been able to prevent this dysfunction from being expressed as a nosocomial infection,” said Dr. Maier.

The genomic analysis can also be used to discriminate patients who regain homeostasis relatively quickly after severe trauma. There seems to be an inflection point between patients who resolve by 5 days and those who go on to experience prolonged ICU stays.

Perhaps surprisingly, the researchers found little difference between the two groups in terms of specific genes that were up- or down-regulated. Instead, the “uncomplicated” group saw their altered gene expression patterns return more quickly to baseline levels, whereas “complicated” patients lingered in the dysregulated state. “We’ve been chasing biomarkers for 35 years, and this explains why it’s very difficult. Those who do well return toward normal quickly. Those who have complications stay abnormal,” said Dr. Maier.

Instead, researchers identified a panel of 63 gene probes that can track the overall progress of the “genomic storm,” as he referred to the changes that occur in the wake of trauma. “This panel of 63 genes is the best predictor of the patient’s response to injury – better than injury severity score, better than multiple organ failure scores,” he said.

Dr. Maier is confident that such panels can alter patient management, even outside of trauma. “It may allow us to show which patients are going to have risk of early recurrence because of alterations in their adaptive immunity versus those who aren’t. We’re also going to predict those who are going to have infectious complications. Hopefully we’ll soon have a handle on which patients we need to be most aggressive with, and we can use monitoring to measure our therapeutic impact,” said Dr. Maier.
 

email address

SOURCE: Add the first author et al., journal citation/abstract number, and hyperlink it here.

SAN DIEGO – A simplified version of the Sequential Organ Failure Assessment (SOFA) criteria, known as eSOFA, has the potential to make it easier for hospitals to benchmark sepsis outcomes and quality of care, and could propel new sepsis research. The new method replaces some of SOFA’s more subjective criteria with objective measures.

eSOFA relies on electronic health records to reduce reliance on administrative records, which suffer from cross-hospital variability in diagnosis and coding practices, as well as changes in these practices over time. The diagnosis of sepsis itself is also highly subjective. Instead, eSOFA determines dysfunction in six organ systems, indicated by use of vasopressors and mechanical ventilation, and the presence of abnormal laboratory values.

“The SOFA score includes measures like the Glasgow Coma Scale, which undoubtedly at the bedside is a very important clinical sign, but when trying to implement something that is objective for purposes of retrospective case counting and standardization, it can be problematic. The measures we chose [for eSOFA] are concrete, important maneuvers that were initiated by clinicians,” Chanu Rhee, MD, said in an interview.

Dr. Rhee is assistant professor of population medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston. He presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine, and the work was simultaneously published online in Critical Care Medicine.

Key elements of SOFA that pose challenges for administrative data include: PaO₂/FiO₂, which are not routinely measured, and can be difficult to assign to arterial or venous samples; inconsistency in blood pressure and transient increases in vasopressor dose; the subjectivity of the Glasgow Coma Scale, which is also difficult to assess in sedated patients; and inconsistent urine output.

eSOFA introduced new measures for various organ functions, including cardiovascular (vasopressor initiation), pulmonary (mechanical ventilation initiation), renal (doubling of creatinine levels or a 50% or greater decrease in estimated glomerular filtration rate, compared with baseline), hepatic (bilirubin levels greater than or equal to 2.0 mg/dL and at least doubled from baseline), coagulation (platelet count less than 100 cells/mcL and at least a 50% decrease from a baseline of at least 100 cells/mcL), and neurological (lactate greater than or equal to 2.0 mmol/L).

“[eSOFA] opens a window into inter-facility comparisons that has not been possible to do. It’s really critical to ask, ‘How am I doing compared to my peer institutions?’ If you’re doing worse, you can look at the whole spectrum of things to try to drive improvements in care,” said Dr. Rhee.

The new tool isn’t just limited to quality improvement research. Shaeesta Khan, MD, assistant professor of critical care medicine at Geisinger Medical Center,Danville, Pa., has found eSOFA to be useful in her research into how genetic polymorphisms play a role in sepsis outcomes. Geisinger has a large population of patients with completed whole genome sequencing, and Dr. Khan began by trying to glean sepsis outcomes from administrative data.

“I explained SOFA scores to our data broker, and he pulled up 3,000 patients and gave everybody a SOFA score based on the algorithm he created, and it was all over the chart. Once I started doing chart review and phenotype verification, it was just a nightmare,” Dr. Khan said in an interview.

After struggling with the project, one of her mentors put her in touch with one of Dr. Rhee’s colleagues, and she asked the data broker to modify the eSOFA algorithm to fit her specific criteria. “It was a blessing,” she said.

Now, she has data from 5,000 patients with sepsis and sequenced DNA, and can begin comparing outcomes and genetic variants. About 20 candidate genes for sepsis outcomes have been identified to date, but she has a particular interest in PCSK9, which is an innate immune system regulator. She hopes to present results at CCC49 in 2020.
 

Validating mortality prediction

The researchers compared eSOFA and SOFA in a sample from 111 U.S. acute care hospitals to see if eSOFA had a comparable predictive validity for mortality. The analysis included 942,360 adults seen between 2013 and 2015. A total of 11.1% (104,903) had a presumed serious infection based on a blood culture order and at least 4 consecutive days of antibiotic use.

The analysis showed that 6.1% of those with infections had a sepsis event based on at least a 2-point increase in SOFA score from baseline (Sepsis-3 criteria), compared with 4.4% identified by at least a 1-point increase in eSOFA score. A total of 34,174 patients (3.6%) overlapped between SOFA and eSOFA, which represented good agreement (Cronbach’s alpha, 0.81). Compared with SOFA/Sepsis-3, eSOFA had a sensitivity of 60%, and a positive predictive value of 82%.

Patients identified by eSOFA were slightly more ill, with more requiring ICU admission (41% vs. 35%), and a greater frequency of in-hospital mortality (17% vs. 14%). Those patients who were identified by SOFA/Sepsis-3, but missed by eSOFA, had an overall lower mortality (6%).

There was a similar risk of mortality across deciles between SOFA- and eSOFA-identified sepsis patients. In an independent analysis of four hospitals from the Emory system, the area under the receiver operating characteristics was 0.77 for eSOFA and 0.76 for SOFA (P less than .001).

The Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality funded the study. Dr. Rhee and Dr. Khan have no relevant financial conflicts.
 

SOURCE: Rhee C et al. Crit Care Med. 2019;47(3):307-14.

SAN DIEGO – A simplified version of the Sequential Organ Failure Assessment (SOFA) criteria, known as eSOFA, has the potential to make it easier for hospitals to benchmark sepsis outcomes and quality of care, and could propel new sepsis research. The new method replaces some of SOFA’s more subjective criteria with objective measures.

eSOFA relies on electronic health records to reduce reliance on administrative records, which suffer from cross-hospital variability in diagnosis and coding practices, as well as changes in these practices over time. The diagnosis of sepsis itself is also highly subjective. Instead, eSOFA determines dysfunction in six organ systems, indicated by use of vasopressors and mechanical ventilation, and the presence of abnormal laboratory values.

“The SOFA score includes measures like the Glasgow Coma Scale, which undoubtedly at the bedside is a very important clinical sign, but when trying to implement something that is objective for purposes of retrospective case counting and standardization, it can be problematic. The measures we chose [for eSOFA] are concrete, important maneuvers that were initiated by clinicians,” Chanu Rhee, MD, said in an interview.

Dr. Rhee is assistant professor of population medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston. He presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine, and the work was simultaneously published online in Critical Care Medicine.

Key elements of SOFA that pose challenges for administrative data include: PaO₂/FiO₂, which are not routinely measured, and can be difficult to assign to arterial or venous samples; inconsistency in blood pressure and transient increases in vasopressor dose; the subjectivity of the Glasgow Coma Scale, which is also difficult to assess in sedated patients; and inconsistent urine output.

eSOFA introduced new measures for various organ functions, including cardiovascular (vasopressor initiation), pulmonary (mechanical ventilation initiation), renal (doubling of creatinine levels or a 50% or greater decrease in estimated glomerular filtration rate, compared with baseline), hepatic (bilirubin levels greater than or equal to 2.0 mg/dL and at least doubled from baseline), coagulation (platelet count less than 100 cells/mcL and at least a 50% decrease from a baseline of at least 100 cells/mcL), and neurological (lactate greater than or equal to 2.0 mmol/L).

“[eSOFA] opens a window into inter-facility comparisons that has not been possible to do. It’s really critical to ask, ‘How am I doing compared to my peer institutions?’ If you’re doing worse, you can look at the whole spectrum of things to try to drive improvements in care,” said Dr. Rhee.

The new tool isn’t just limited to quality improvement research. Shaeesta Khan, MD, assistant professor of critical care medicine at Geisinger Medical Center,Danville, Pa., has found eSOFA to be useful in her research into how genetic polymorphisms play a role in sepsis outcomes. Geisinger has a large population of patients with completed whole genome sequencing, and Dr. Khan began by trying to glean sepsis outcomes from administrative data.

“I explained SOFA scores to our data broker, and he pulled up 3,000 patients and gave everybody a SOFA score based on the algorithm he created, and it was all over the chart. Once I started doing chart review and phenotype verification, it was just a nightmare,” Dr. Khan said in an interview.

After struggling with the project, one of her mentors put her in touch with one of Dr. Rhee’s colleagues, and she asked the data broker to modify the eSOFA algorithm to fit her specific criteria. “It was a blessing,” she said.

Now, she has data from 5,000 patients with sepsis and sequenced DNA, and can begin comparing outcomes and genetic variants. About 20 candidate genes for sepsis outcomes have been identified to date, but she has a particular interest in PCSK9, which is an innate immune system regulator. She hopes to present results at CCC49 in 2020.
 

Validating mortality prediction

The researchers compared eSOFA and SOFA in a sample from 111 U.S. acute care hospitals to see if eSOFA had a comparable predictive validity for mortality. The analysis included 942,360 adults seen between 2013 and 2015. A total of 11.1% (104,903) had a presumed serious infection based on a blood culture order and at least 4 consecutive days of antibiotic use.

The analysis showed that 6.1% of those with infections had a sepsis event based on at least a 2-point increase in SOFA score from baseline (Sepsis-3 criteria), compared with 4.4% identified by at least a 1-point increase in eSOFA score. A total of 34,174 patients (3.6%) overlapped between SOFA and eSOFA, which represented good agreement (Cronbach’s alpha, 0.81). Compared with SOFA/Sepsis-3, eSOFA had a sensitivity of 60%, and a positive predictive value of 82%.

Patients identified by eSOFA were slightly more ill, with more requiring ICU admission (41% vs. 35%), and a greater frequency of in-hospital mortality (17% vs. 14%). Those patients who were identified by SOFA/Sepsis-3, but missed by eSOFA, had an overall lower mortality (6%).

There was a similar risk of mortality across deciles between SOFA- and eSOFA-identified sepsis patients. In an independent analysis of four hospitals from the Emory system, the area under the receiver operating characteristics was 0.77 for eSOFA and 0.76 for SOFA (P less than .001).

The Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality funded the study. Dr. Rhee and Dr. Khan have no relevant financial conflicts.
 

SOURCE: Rhee C et al. Crit Care Med. 2019;47(3):307-14.

SAN DIEGO – A simplified version of the Sequential Organ Failure Assessment (SOFA) criteria, known as eSOFA, has the potential to make it easier for hospitals to benchmark sepsis outcomes and quality of care, and could propel new sepsis research. The new method replaces some of SOFA’s more subjective criteria with objective measures.

eSOFA relies on electronic health records to reduce reliance on administrative records, which suffer from cross-hospital variability in diagnosis and coding practices, as well as changes in these practices over time. The diagnosis of sepsis itself is also highly subjective. Instead, eSOFA determines dysfunction in six organ systems, indicated by use of vasopressors and mechanical ventilation, and the presence of abnormal laboratory values.

“The SOFA score includes measures like the Glasgow Coma Scale, which undoubtedly at the bedside is a very important clinical sign, but when trying to implement something that is objective for purposes of retrospective case counting and standardization, it can be problematic. The measures we chose [for eSOFA] are concrete, important maneuvers that were initiated by clinicians,” Chanu Rhee, MD, said in an interview.

Dr. Rhee is assistant professor of population medicine at Harvard Medical School and Brigham and Women’s Hospital, Boston. He presented the results of the study at the Critical Care Congress sponsored by the Society of Critical Care Medicine, and the work was simultaneously published online in Critical Care Medicine.

Key elements of SOFA that pose challenges for administrative data include: PaO₂/FiO₂, which are not routinely measured, and can be difficult to assign to arterial or venous samples; inconsistency in blood pressure and transient increases in vasopressor dose; the subjectivity of the Glasgow Coma Scale, which is also difficult to assess in sedated patients; and inconsistent urine output.

eSOFA introduced new measures for various organ functions, including cardiovascular (vasopressor initiation), pulmonary (mechanical ventilation initiation), renal (doubling of creatinine levels or a 50% or greater decrease in estimated glomerular filtration rate, compared with baseline), hepatic (bilirubin levels greater than or equal to 2.0 mg/dL and at least doubled from baseline), coagulation (platelet count less than 100 cells/mcL and at least a 50% decrease from a baseline of at least 100 cells/mcL), and neurological (lactate greater than or equal to 2.0 mmol/L).

“[eSOFA] opens a window into inter-facility comparisons that has not been possible to do. It’s really critical to ask, ‘How am I doing compared to my peer institutions?’ If you’re doing worse, you can look at the whole spectrum of things to try to drive improvements in care,” said Dr. Rhee.

The new tool isn’t just limited to quality improvement research. Shaeesta Khan, MD, assistant professor of critical care medicine at Geisinger Medical Center,Danville, Pa., has found eSOFA to be useful in her research into how genetic polymorphisms play a role in sepsis outcomes. Geisinger has a large population of patients with completed whole genome sequencing, and Dr. Khan began by trying to glean sepsis outcomes from administrative data.

“I explained SOFA scores to our data broker, and he pulled up 3,000 patients and gave everybody a SOFA score based on the algorithm he created, and it was all over the chart. Once I started doing chart review and phenotype verification, it was just a nightmare,” Dr. Khan said in an interview.

After struggling with the project, one of her mentors put her in touch with one of Dr. Rhee’s colleagues, and she asked the data broker to modify the eSOFA algorithm to fit her specific criteria. “It was a blessing,” she said.

Now, she has data from 5,000 patients with sepsis and sequenced DNA, and can begin comparing outcomes and genetic variants. About 20 candidate genes for sepsis outcomes have been identified to date, but she has a particular interest in PCSK9, which is an innate immune system regulator. She hopes to present results at CCC49 in 2020.
 

Validating mortality prediction

The researchers compared eSOFA and SOFA in a sample from 111 U.S. acute care hospitals to see if eSOFA had a comparable predictive validity for mortality. The analysis included 942,360 adults seen between 2013 and 2015. A total of 11.1% (104,903) had a presumed serious infection based on a blood culture order and at least 4 consecutive days of antibiotic use.

The analysis showed that 6.1% of those with infections had a sepsis event based on at least a 2-point increase in SOFA score from baseline (Sepsis-3 criteria), compared with 4.4% identified by at least a 1-point increase in eSOFA score. A total of 34,174 patients (3.6%) overlapped between SOFA and eSOFA, which represented good agreement (Cronbach’s alpha, 0.81). Compared with SOFA/Sepsis-3, eSOFA had a sensitivity of 60%, and a positive predictive value of 82%.

Patients identified by eSOFA were slightly more ill, with more requiring ICU admission (41% vs. 35%), and a greater frequency of in-hospital mortality (17% vs. 14%). Those patients who were identified by SOFA/Sepsis-3, but missed by eSOFA, had an overall lower mortality (6%).

There was a similar risk of mortality across deciles between SOFA- and eSOFA-identified sepsis patients. In an independent analysis of four hospitals from the Emory system, the area under the receiver operating characteristics was 0.77 for eSOFA and 0.76 for SOFA (P less than .001).

The Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality funded the study. Dr. Rhee and Dr. Khan have no relevant financial conflicts.
 

SOURCE: Rhee C et al. Crit Care Med. 2019;47(3):307-14.

SAN DIEGO – When attempting a second extubation, improvements in weaning parameters, compared with the first extubation attempt, do not predict success. Instead, the best predictors were the values of the parameters immediately before the second attempt.

“We hypothesized that the change in parameter values was more important than the actual values right before we tried to re-extubate, and that didn’t turn out to be the case. Because it was a smaller study, we can’t say [change in values] is not useful at all, but we didn’t find a strong association. We showed that the magnitude of the effect with the number measured right before the re-extubation is probably your best bet, but you should obviously evaluate the whole clinical scenario,” commented senior author Michael David Maile, MD, assistant professor of anesthesiology at the University of Michigan, Ann Arbor.

The study was presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine by Suraj Trivedi, MD, who is currently an anesthesiology fellow at Stanford (Calif.) Medicine.

Factors such as rapid shallow breathing index (RSBI), negative inspiratory force (NIF), vital capacity (VC), and partial pressure of arterial carbon dioxide (PaCO₂) have been shown to predict success or failure of an initial extubation attempt.

There is currently little available guidance on how to proceed when a first extubation attempt fails. The researchers had anticipated that RSBI, NIF, VC, and PaCO₂ levels matching the first attempt would be associated with success the second time around.

But their retrospective study of adult patients at the University of Michigan critical care units found that only the change in RSBI values predicted success on a univariate analysis, and that association became statistically insignificant once they corrected for baseline RSBI previous to the re-extubation attempt.

“I think the biggest take-home message is that we have to figure out each attempt to extubate on its own merits. If you’re trying to extubate a patient in the ICU who has potentially been intubated and extubated multiple times, the clinical gut feeling is always that [the patient has] to be better off than the previous attempt. What we are pointing out is that it really doesn’t matter. If the parameters are all within the overall guidelines, it’s still okay to extubate, even if the absolute change in the variables is not better [than the previous attempt],” Dr. Trivedi said in an interview.

“People put a lot of emphasis on the improvement from the first to the second attempt, and this should temper that enthusiasm to put a lot of weight on the change. But I don’t think our data support that the change means nothing,” added Dr. Maile.

The study included 525 patients (42% female). Comorbidities were common: 72% had cardiac arrhythmias, 58% had hypertension, 33% had renal failure, 39% had a pulmonary disorder, and 25% had liver disease.

Univariate analyses showed associations between values of parameters immediately before the second extubation attempt and success in the second extubation attempt, including RSBI (re-extubation success, mean 53.1 vs failure, mean 68.8; P =.0002) and NIF (success, mean –41.2 vs. failure, mean –38.4; P =.036), and VC (success, mean 1009.8 vs. failure, mean 906.8; P =.017).

When the researchers examined changes in parameters between the first and second attempt, only a change in RSBI predicted success (success, value change of 7.1 vs. failure, value change of 0.05; P less than .031). But when they corrected for the RSBI value immediately before the second attempt, the difference was not statistically significant (P = .892).

The study was not funded. Dr. Maile and Dr. Trivedi have no relevant financial disclosures.

SOURCE: Trivedi S et al. CCC48 2019, Abstract 27.

SAN DIEGO – When attempting a second extubation, improvements in weaning parameters, compared with the first extubation attempt, do not predict success. Instead, the best predictors were the values of the parameters immediately before the second attempt.

“We hypothesized that the change in parameter values was more important than the actual values right before we tried to re-extubate, and that didn’t turn out to be the case. Because it was a smaller study, we can’t say [change in values] is not useful at all, but we didn’t find a strong association. We showed that the magnitude of the effect with the number measured right before the re-extubation is probably your best bet, but you should obviously evaluate the whole clinical scenario,” commented senior author Michael David Maile, MD, assistant professor of anesthesiology at the University of Michigan, Ann Arbor.

The study was presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine by Suraj Trivedi, MD, who is currently an anesthesiology fellow at Stanford (Calif.) Medicine.

Factors such as rapid shallow breathing index (RSBI), negative inspiratory force (NIF), vital capacity (VC), and partial pressure of arterial carbon dioxide (PaCO₂) have been shown to predict success or failure of an initial extubation attempt.

There is currently little available guidance on how to proceed when a first extubation attempt fails. The researchers had anticipated that RSBI, NIF, VC, and PaCO₂ levels matching the first attempt would be associated with success the second time around.

But their retrospective study of adult patients at the University of Michigan critical care units found that only the change in RSBI values predicted success on a univariate analysis, and that association became statistically insignificant once they corrected for baseline RSBI previous to the re-extubation attempt.

“I think the biggest take-home message is that we have to figure out each attempt to extubate on its own merits. If you’re trying to extubate a patient in the ICU who has potentially been intubated and extubated multiple times, the clinical gut feeling is always that [the patient has] to be better off than the previous attempt. What we are pointing out is that it really doesn’t matter. If the parameters are all within the overall guidelines, it’s still okay to extubate, even if the absolute change in the variables is not better [than the previous attempt],” Dr. Trivedi said in an interview.

“People put a lot of emphasis on the improvement from the first to the second attempt, and this should temper that enthusiasm to put a lot of weight on the change. But I don’t think our data support that the change means nothing,” added Dr. Maile.

The study included 525 patients (42% female). Comorbidities were common: 72% had cardiac arrhythmias, 58% had hypertension, 33% had renal failure, 39% had a pulmonary disorder, and 25% had liver disease.

Univariate analyses showed associations between values of parameters immediately before the second extubation attempt and success in the second extubation attempt, including RSBI (re-extubation success, mean 53.1 vs failure, mean 68.8; P =.0002) and NIF (success, mean –41.2 vs. failure, mean –38.4; P =.036), and VC (success, mean 1009.8 vs. failure, mean 906.8; P =.017).

When the researchers examined changes in parameters between the first and second attempt, only a change in RSBI predicted success (success, value change of 7.1 vs. failure, value change of 0.05; P less than .031). But when they corrected for the RSBI value immediately before the second attempt, the difference was not statistically significant (P = .892).

The study was not funded. Dr. Maile and Dr. Trivedi have no relevant financial disclosures.

SOURCE: Trivedi S et al. CCC48 2019, Abstract 27.

SAN DIEGO – When attempting a second extubation, improvements in weaning parameters, compared with the first extubation attempt, do not predict success. Instead, the best predictors were the values of the parameters immediately before the second attempt.

“We hypothesized that the change in parameter values was more important than the actual values right before we tried to re-extubate, and that didn’t turn out to be the case. Because it was a smaller study, we can’t say [change in values] is not useful at all, but we didn’t find a strong association. We showed that the magnitude of the effect with the number measured right before the re-extubation is probably your best bet, but you should obviously evaluate the whole clinical scenario,” commented senior author Michael David Maile, MD, assistant professor of anesthesiology at the University of Michigan, Ann Arbor.

The study was presented at the Critical Care Congress sponsored by the Society of Critical Care Medicine by Suraj Trivedi, MD, who is currently an anesthesiology fellow at Stanford (Calif.) Medicine.

Factors such as rapid shallow breathing index (RSBI), negative inspiratory force (NIF), vital capacity (VC), and partial pressure of arterial carbon dioxide (PaCO₂) have been shown to predict success or failure of an initial extubation attempt.

There is currently little available guidance on how to proceed when a first extubation attempt fails. The researchers had anticipated that RSBI, NIF, VC, and PaCO₂ levels matching the first attempt would be associated with success the second time around.

But their retrospective study of adult patients at the University of Michigan critical care units found that only the change in RSBI values predicted success on a univariate analysis, and that association became statistically insignificant once they corrected for baseline RSBI previous to the re-extubation attempt.

“I think the biggest take-home message is that we have to figure out each attempt to extubate on its own merits. If you’re trying to extubate a patient in the ICU who has potentially been intubated and extubated multiple times, the clinical gut feeling is always that [the patient has] to be better off than the previous attempt. What we are pointing out is that it really doesn’t matter. If the parameters are all within the overall guidelines, it’s still okay to extubate, even if the absolute change in the variables is not better [than the previous attempt],” Dr. Trivedi said in an interview.

“People put a lot of emphasis on the improvement from the first to the second attempt, and this should temper that enthusiasm to put a lot of weight on the change. But I don’t think our data support that the change means nothing,” added Dr. Maile.

The study included 525 patients (42% female). Comorbidities were common: 72% had cardiac arrhythmias, 58% had hypertension, 33% had renal failure, 39% had a pulmonary disorder, and 25% had liver disease.

Univariate analyses showed associations between values of parameters immediately before the second extubation attempt and success in the second extubation attempt, including RSBI (re-extubation success, mean 53.1 vs failure, mean 68.8; P =.0002) and NIF (success, mean –41.2 vs. failure, mean –38.4; P =.036), and VC (success, mean 1009.8 vs. failure, mean 906.8; P =.017).

When the researchers examined changes in parameters between the first and second attempt, only a change in RSBI predicted success (success, value change of 7.1 vs. failure, value change of 0.05; P less than .031). But when they corrected for the RSBI value immediately before the second attempt, the difference was not statistically significant (P = .892).

The study was not funded. Dr. Maile and Dr. Trivedi have no relevant financial disclosures.

SOURCE: Trivedi S et al. CCC48 2019, Abstract 27.