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Small-volume blood sample tubes may reduce anemia and transfusions in intensive care
according to a new study. The change does not appear to impair biospecimen sufficiency for lab analysis.
In addition, by reducing blood transfusion during ICU admission by about 10 units per 100 patients, the change may enable hospitals and health systems to sustain blood product supply during ongoing worldwide shortages.
“It doesn’t take long working in a hospital or being a patient or family member to realize how much blood we take to do lab work. As a result, patients may develop anemia and low RBC counts, which can be associated with worse health outcomes,” lead author Deborah Siegal, MD, a hematologist at the Ottawa Hospital and associate professor of medicine at the University of Ottawa, said in an interview.
“Unfortunately, the majority of the blood we take is discarded as waste,” she said. “Here’s an opportunity to move the needle on reducing anemia in hospitalized patients, where the benefit also doesn’t come at a cost.”
The study was published online in JAMA.
Reducing Blood Loss
Among ICU patients with critical illness, there is a high prevalence of anemia, Siegal noted. More than 90% of these patients have some degree of anemia after a 3-day stay. Typically, RBC transfusions are given to correct the low blood counts, and as many as 40% of ICU patients receive at least one RBC transfusion. Anemia and RBC transfusion are each associated with adverse outcomes, including higher mortality and longer ICU and hospital stays.
Although anemia in critically ill ICU patients can have several causes, blood sampling can be substantial because of the need to draw multiple tubes several times per day. During 8 days in an ICU, the amount of blood drawn equals about 1 unit of whole blood, the authors noted, and ICU patients often struggle to increase RBC production and compensate for blood loss.
Even then, only 10% of the blood collected is required for lab testing; the remaining 90% is often discarded as waste, the authors noted. Small-volume tubes (1.8 to 3.5 mL), which are designed to draw about 50% less than standard-volume tubes (4 to 6 mL) by using less vacuum strength, are of the same size and cost as standard-volume tubes, and the collection technique is the same. They are produced by the same manufacturers and are compatible with existing lab equipment.
Siegal and colleagues conducted a stepped-wedge cluster randomized trial to test the switch to small-volume tubes in 25 adult medical-surgical ICUs in Canada between February 2019 and January 2021. They analyzed data from more than 27,000 patients admitted to the ICU for 48 hours or longer. ICUs were randomly assigned to switch from standard-volume tubes to small-volume tubes for lab testing. The research team primarily assessed RBC transfusion in units per patient per ICU stay, as well as hemoglobin decrease during ICU stay, length of stay in the ICU and hospital, mortality in the ICU and hospital, and specimen tubes with insufficient volume for testing.
In a primary analysis of 21,201 patients, which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference between tube-volume groups in RBC units per patient per ICU stay (relative risk [RR], 0.91). However, there was an absolute reduction of 7.24 RBC units per 100 patients per ICU stay in the small-volume group.
In addition, in a prespecified secondary analysis of 27,411 patients, RBC units per patient per ICU stay significantly decreased (RR, 0.88) after the switch to small-volume tubes, and there was an absolute reduction of 9.84 RBC units per 100 patients per ICU stay.
Overall, the median decrease in transfusion-adjusted hemoglobin wasn’t significantly different in the primary analysis but was lower in the secondary analysis. The frequency of specimens with insufficient volume for testing was low (≤0.03%) before and after the transition to small-volume tubes.
About 36,000 units of blood were given to ICU patients during the study period. The use of small-volume tubes may have saved about 1500 RBC units, the authors estimated.
“This could be an important way to help preserve the supply of blood products for patients who need them, including those undergoing cancer treatment, surgery, trauma, or other medical illnesses,” Siegal said. “The other great aspect is that this was implemented by people on the ground in the ICUs, and it’s still in use in most of those hospitals today.”
The investigators noted the need to study the switch in other patient populations, such as non-ICU hospitalized patients or outpatient settings. For instance, ICU patients often have central venous or arterial catheters for blood draws, but small-volume tubes can be used with venipuncture and could lead to additional benefits there as well.
Implementing Change
Commenting on the findings for this article, Lisa Hicks, MD, a hematologist at St. Michael’s Hospital and associate professor of medicine at the University of Toronto, said, “Routinely collecting smaller volumes of blood for diagnostic testing appears to be feasible and does not cause problems with inadequate sampling. Whether this strategy decreases transfusion is more complicated.” Hicks did not participate in the study.
“At the end of the day, we still don’t know with certainty whether reduced-volume blood collection tubes decrease transfusion burden in ICU patients — it’s possible that there are so many other factors driving down hemoglobin in this population that the impact of blood collection volume is modest to negligible,” she said. “On the other hand, it’s also possible that there is an important impact that was masked by the relatively short ICU stays in the included population.”
Hicks has researched ways to reduce unnecessary diagnostic phlebotomy in ICUs. She and colleagues found that targeting clinicians’ test ordering behavior can decrease blood draws and RBC transfusions.
“What we now know, thanks to Siegal et al, is that we don’t need to collect nearly as much blood from our ICU patients as we do, raising the question of which strategy should really be standard,” she said. “My vote goes for more blood in the patient and less in the bin.”
The study was funded by a peer-reviewed grant from the Academic Health Sciences Centers AFP Innovation Fund/Hamilton Academic Health Sciences Organization and the Hamilton Health Sciences Research Institute through the Population Health Research Institute. Siegal, who is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease, reported honoraria for presentations paid indirectly to her institution from BMS-Pfizer, AstraZeneca, Servier, and Roche outside of the submitted work. Hicks reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
according to a new study. The change does not appear to impair biospecimen sufficiency for lab analysis.
In addition, by reducing blood transfusion during ICU admission by about 10 units per 100 patients, the change may enable hospitals and health systems to sustain blood product supply during ongoing worldwide shortages.
“It doesn’t take long working in a hospital or being a patient or family member to realize how much blood we take to do lab work. As a result, patients may develop anemia and low RBC counts, which can be associated with worse health outcomes,” lead author Deborah Siegal, MD, a hematologist at the Ottawa Hospital and associate professor of medicine at the University of Ottawa, said in an interview.
“Unfortunately, the majority of the blood we take is discarded as waste,” she said. “Here’s an opportunity to move the needle on reducing anemia in hospitalized patients, where the benefit also doesn’t come at a cost.”
The study was published online in JAMA.
Reducing Blood Loss
Among ICU patients with critical illness, there is a high prevalence of anemia, Siegal noted. More than 90% of these patients have some degree of anemia after a 3-day stay. Typically, RBC transfusions are given to correct the low blood counts, and as many as 40% of ICU patients receive at least one RBC transfusion. Anemia and RBC transfusion are each associated with adverse outcomes, including higher mortality and longer ICU and hospital stays.
Although anemia in critically ill ICU patients can have several causes, blood sampling can be substantial because of the need to draw multiple tubes several times per day. During 8 days in an ICU, the amount of blood drawn equals about 1 unit of whole blood, the authors noted, and ICU patients often struggle to increase RBC production and compensate for blood loss.
Even then, only 10% of the blood collected is required for lab testing; the remaining 90% is often discarded as waste, the authors noted. Small-volume tubes (1.8 to 3.5 mL), which are designed to draw about 50% less than standard-volume tubes (4 to 6 mL) by using less vacuum strength, are of the same size and cost as standard-volume tubes, and the collection technique is the same. They are produced by the same manufacturers and are compatible with existing lab equipment.
Siegal and colleagues conducted a stepped-wedge cluster randomized trial to test the switch to small-volume tubes in 25 adult medical-surgical ICUs in Canada between February 2019 and January 2021. They analyzed data from more than 27,000 patients admitted to the ICU for 48 hours or longer. ICUs were randomly assigned to switch from standard-volume tubes to small-volume tubes for lab testing. The research team primarily assessed RBC transfusion in units per patient per ICU stay, as well as hemoglobin decrease during ICU stay, length of stay in the ICU and hospital, mortality in the ICU and hospital, and specimen tubes with insufficient volume for testing.
In a primary analysis of 21,201 patients, which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference between tube-volume groups in RBC units per patient per ICU stay (relative risk [RR], 0.91). However, there was an absolute reduction of 7.24 RBC units per 100 patients per ICU stay in the small-volume group.
In addition, in a prespecified secondary analysis of 27,411 patients, RBC units per patient per ICU stay significantly decreased (RR, 0.88) after the switch to small-volume tubes, and there was an absolute reduction of 9.84 RBC units per 100 patients per ICU stay.
Overall, the median decrease in transfusion-adjusted hemoglobin wasn’t significantly different in the primary analysis but was lower in the secondary analysis. The frequency of specimens with insufficient volume for testing was low (≤0.03%) before and after the transition to small-volume tubes.
About 36,000 units of blood were given to ICU patients during the study period. The use of small-volume tubes may have saved about 1500 RBC units, the authors estimated.
“This could be an important way to help preserve the supply of blood products for patients who need them, including those undergoing cancer treatment, surgery, trauma, or other medical illnesses,” Siegal said. “The other great aspect is that this was implemented by people on the ground in the ICUs, and it’s still in use in most of those hospitals today.”
The investigators noted the need to study the switch in other patient populations, such as non-ICU hospitalized patients or outpatient settings. For instance, ICU patients often have central venous or arterial catheters for blood draws, but small-volume tubes can be used with venipuncture and could lead to additional benefits there as well.
Implementing Change
Commenting on the findings for this article, Lisa Hicks, MD, a hematologist at St. Michael’s Hospital and associate professor of medicine at the University of Toronto, said, “Routinely collecting smaller volumes of blood for diagnostic testing appears to be feasible and does not cause problems with inadequate sampling. Whether this strategy decreases transfusion is more complicated.” Hicks did not participate in the study.
“At the end of the day, we still don’t know with certainty whether reduced-volume blood collection tubes decrease transfusion burden in ICU patients — it’s possible that there are so many other factors driving down hemoglobin in this population that the impact of blood collection volume is modest to negligible,” she said. “On the other hand, it’s also possible that there is an important impact that was masked by the relatively short ICU stays in the included population.”
Hicks has researched ways to reduce unnecessary diagnostic phlebotomy in ICUs. She and colleagues found that targeting clinicians’ test ordering behavior can decrease blood draws and RBC transfusions.
“What we now know, thanks to Siegal et al, is that we don’t need to collect nearly as much blood from our ICU patients as we do, raising the question of which strategy should really be standard,” she said. “My vote goes for more blood in the patient and less in the bin.”
The study was funded by a peer-reviewed grant from the Academic Health Sciences Centers AFP Innovation Fund/Hamilton Academic Health Sciences Organization and the Hamilton Health Sciences Research Institute through the Population Health Research Institute. Siegal, who is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease, reported honoraria for presentations paid indirectly to her institution from BMS-Pfizer, AstraZeneca, Servier, and Roche outside of the submitted work. Hicks reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
according to a new study. The change does not appear to impair biospecimen sufficiency for lab analysis.
In addition, by reducing blood transfusion during ICU admission by about 10 units per 100 patients, the change may enable hospitals and health systems to sustain blood product supply during ongoing worldwide shortages.
“It doesn’t take long working in a hospital or being a patient or family member to realize how much blood we take to do lab work. As a result, patients may develop anemia and low RBC counts, which can be associated with worse health outcomes,” lead author Deborah Siegal, MD, a hematologist at the Ottawa Hospital and associate professor of medicine at the University of Ottawa, said in an interview.
“Unfortunately, the majority of the blood we take is discarded as waste,” she said. “Here’s an opportunity to move the needle on reducing anemia in hospitalized patients, where the benefit also doesn’t come at a cost.”
The study was published online in JAMA.
Reducing Blood Loss
Among ICU patients with critical illness, there is a high prevalence of anemia, Siegal noted. More than 90% of these patients have some degree of anemia after a 3-day stay. Typically, RBC transfusions are given to correct the low blood counts, and as many as 40% of ICU patients receive at least one RBC transfusion. Anemia and RBC transfusion are each associated with adverse outcomes, including higher mortality and longer ICU and hospital stays.
Although anemia in critically ill ICU patients can have several causes, blood sampling can be substantial because of the need to draw multiple tubes several times per day. During 8 days in an ICU, the amount of blood drawn equals about 1 unit of whole blood, the authors noted, and ICU patients often struggle to increase RBC production and compensate for blood loss.
Even then, only 10% of the blood collected is required for lab testing; the remaining 90% is often discarded as waste, the authors noted. Small-volume tubes (1.8 to 3.5 mL), which are designed to draw about 50% less than standard-volume tubes (4 to 6 mL) by using less vacuum strength, are of the same size and cost as standard-volume tubes, and the collection technique is the same. They are produced by the same manufacturers and are compatible with existing lab equipment.
Siegal and colleagues conducted a stepped-wedge cluster randomized trial to test the switch to small-volume tubes in 25 adult medical-surgical ICUs in Canada between February 2019 and January 2021. They analyzed data from more than 27,000 patients admitted to the ICU for 48 hours or longer. ICUs were randomly assigned to switch from standard-volume tubes to small-volume tubes for lab testing. The research team primarily assessed RBC transfusion in units per patient per ICU stay, as well as hemoglobin decrease during ICU stay, length of stay in the ICU and hospital, mortality in the ICU and hospital, and specimen tubes with insufficient volume for testing.
In a primary analysis of 21,201 patients, which excluded 6210 patients admitted during the early COVID-19 pandemic, there was no significant difference between tube-volume groups in RBC units per patient per ICU stay (relative risk [RR], 0.91). However, there was an absolute reduction of 7.24 RBC units per 100 patients per ICU stay in the small-volume group.
In addition, in a prespecified secondary analysis of 27,411 patients, RBC units per patient per ICU stay significantly decreased (RR, 0.88) after the switch to small-volume tubes, and there was an absolute reduction of 9.84 RBC units per 100 patients per ICU stay.
Overall, the median decrease in transfusion-adjusted hemoglobin wasn’t significantly different in the primary analysis but was lower in the secondary analysis. The frequency of specimens with insufficient volume for testing was low (≤0.03%) before and after the transition to small-volume tubes.
About 36,000 units of blood were given to ICU patients during the study period. The use of small-volume tubes may have saved about 1500 RBC units, the authors estimated.
“This could be an important way to help preserve the supply of blood products for patients who need them, including those undergoing cancer treatment, surgery, trauma, or other medical illnesses,” Siegal said. “The other great aspect is that this was implemented by people on the ground in the ICUs, and it’s still in use in most of those hospitals today.”
The investigators noted the need to study the switch in other patient populations, such as non-ICU hospitalized patients or outpatient settings. For instance, ICU patients often have central venous or arterial catheters for blood draws, but small-volume tubes can be used with venipuncture and could lead to additional benefits there as well.
Implementing Change
Commenting on the findings for this article, Lisa Hicks, MD, a hematologist at St. Michael’s Hospital and associate professor of medicine at the University of Toronto, said, “Routinely collecting smaller volumes of blood for diagnostic testing appears to be feasible and does not cause problems with inadequate sampling. Whether this strategy decreases transfusion is more complicated.” Hicks did not participate in the study.
“At the end of the day, we still don’t know with certainty whether reduced-volume blood collection tubes decrease transfusion burden in ICU patients — it’s possible that there are so many other factors driving down hemoglobin in this population that the impact of blood collection volume is modest to negligible,” she said. “On the other hand, it’s also possible that there is an important impact that was masked by the relatively short ICU stays in the included population.”
Hicks has researched ways to reduce unnecessary diagnostic phlebotomy in ICUs. She and colleagues found that targeting clinicians’ test ordering behavior can decrease blood draws and RBC transfusions.
“What we now know, thanks to Siegal et al, is that we don’t need to collect nearly as much blood from our ICU patients as we do, raising the question of which strategy should really be standard,” she said. “My vote goes for more blood in the patient and less in the bin.”
The study was funded by a peer-reviewed grant from the Academic Health Sciences Centers AFP Innovation Fund/Hamilton Academic Health Sciences Organization and the Hamilton Health Sciences Research Institute through the Population Health Research Institute. Siegal, who is supported by a Tier 2 Canada Research Chair in Anticoagulant Management of Cardiovascular Disease, reported honoraria for presentations paid indirectly to her institution from BMS-Pfizer, AstraZeneca, Servier, and Roche outside of the submitted work. Hicks reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM JAMA
Revisiting the role of hydrocortisone, fludrocortisone in septic shock
Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction,
I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.
It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.
Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
Rethinking hydro/fludro
The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.
In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
Key takeaways
The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.
The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.
A version of this article first appeared on Medscape.com.
Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction,
I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.
It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.
Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
Rethinking hydro/fludro
The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.
In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
Key takeaways
The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.
The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.
A version of this article first appeared on Medscape.com.
Earlier this year, I stumbled across a podcast in a content update email from the Journal of the American Medical Association. The moderator was interviewing the first author of a study comparing hydrocortisone and fludrocortisone (hydro/fludro) to hydrocortisone alone for treatment of septic shock. In the introduction,
I thought this issue had been settled with publication of the COIITSS trial in 2010. This study randomly assigned 509 patients with septic shock to hydro/fludro versus hydrocortisone alone. There was a nonsignificant reduction in mortality with hydro/fludro and everyone I knew stopped adding fludrocortisone for septic shock. It wasn’t included in guidelines (and still isn›t). I figured the only docs still using it were also prescribing ivermectin and vitamin C – another treatment touted to work in an apocryphal podcast.
It wasn’t just COIITSS that killed fludrocortisone for me. Back in 2002, I was a loyal adherent. That year, a randomized controlled trial (RCT) published by “the lord of corticosteroids for critical illness” doctor, Djillali Annane, found benefit to hydro/fludro in septic shock . Everyone in that study had a cosyntropin stim test and only certain subgroups had better outcomes. As a medical resident paying obeisance to all things evidence-based medicine, I rigidly adopted their protocol for all septic patients. I also kept their insulin between 80 and 110 mg/dL, prescribed drotrecogin alfa, and made sure they were floating in crystalloid. But those are topics for another time.
Subsequent trials and meta-analyses cast doubt on the need for the stim test, and a consensus around hydrocortisone at moderate doses for patients with septic shock emerged. Because one part of the Annane protocol was already deemed unnecessary (the cosyntropin stim test), it was easy to dismiss fludrocortisone after COIITTS was published. Yes, I read Annane’s 2018 APROCCHSS trial, and I’m aware that it found that hydro/fludro reduced 90-day mortality. Like others, I rationalized this finding by framing it as a function of baseline mortality. The two Annane RCTs that found that hydro/fludro reduced mortality in enrolled patients who were considerably more likely to die than those enrolled in RCTs of hydrocortisone alone were negative. It was the target population mortality rate and not the addition of fludrocortisone that made the difference, right?
Rethinking hydro/fludro
The author interviewed for the recent JAMA podcast forced me to rethink my blithe dismissal of fludrocortisone. He contended that the COIITTS trial was underpowered and the two Annane RCTs that used fludrocortisone supply the evidence that shows corticosteroids reduce septic shock mortality. As discussed earlier, he found clinical equipoise among his colleagues. Last, he invoked pleiotropic mineralocorticoid effects, such as activation of innate immunity and clearance of alveolar fluid, to support the need to reexamine hydro/fludro.
In his study, he used Big Data to compare hospital records from 2016 to 2020. He analyzed a total of 88,275 patients with septic shock. Most were prescribed hydrocortisone alone (85,995 [97.4%] vs. only 2.6% hydro/fludro). After a number of statistical adjustments and sensitivity analyses, the authors concluded that the addition of fludrocortisone to hydrocortisone for patients with septic shock provides a 3.7% absolute risk reduction in mortality (or discharge to hospice) when compared with hydrocortisone alone. That’s a number needed to treat of 28 to prevent one death (or discharge to hospice).
Key takeaways
The study isn’t perfect. In their methods section they use terms like “ensemble machine learner (super learner)” and “immortal time bias.” The first is a fancy way of saying they did a form of propensity scoring, which in turn is a fancy way of saying they tried to control for confounding. The second is a way to adjust for time delays between drug administration. Both are attempts to compensate for the observational design, as is their argument for biologic plausibility. Here they’re on particularly thin ice when trying to prove causal inference. Biologic plausibility is never hard to find; after all, what compound doesn’t have pleiotropic effects? Furthermore, the analysis lacks any data to support their biologic plausibility hypothesis that fludrocortisone’s effect on mortality is mediated via activation of innate immunity and/or clearance of alveolar fluid.
The editorial accompanying this Big Data study endorsed adding fludrocortisone. We have very little that reduces ICU mortality so the low number needed to treat is enticing, especially in light of the low risk from adverse events, so I’m going to start using it. Do I think I’ll save one life for every 28 patients with septic shock to whom I give hydro/fludro instead of hydrocortisone alone? I sure don’t. No way an oral mineralocorticoid at that dose has that type of impact on top of hydrocortisone alone. I still believe that the Annane studies are positive because of the mortality rate in the population enrolled and not because fludrocortisone was added. It all comes full circle, though – 20 years after I abandoned hydro/fludro, I’m going back to it.
Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Md., and a pulmonary/critical care and sleep medicine physician at MedStar Washington Hospital Center in Washington, D.C.
A version of this article first appeared on Medscape.com.
Trial shows utility of small-volume blood collection tubes
A large Canadian clinical trial has found that using small-volume tubes to collect blood samples for laboratory testing of intensive care unit patients can reduce blood transfusions without affecting lab results.
“We showed in a large pragmatic cluster trial that automatically collect less blood for laboratory testing reduced red blood cell transfusions by about 10 units of red blood cells per 100 patients in the ICU,” lead study author Deborah M. Siegal, MD, associate professor at the University of Ottawa and scientist at the Ottawa Hospital Research Institute, said.
The study was coordinated by the Population Health Research Institute, an affiliate of McMaster University in Hamilton (Ont.) Health Sciences, where Dr. Siegal worked before moving to Ottawa.
The STRATUS randomized clinical trial, published in JAMA, involved 25 adult medical-surgical ICUs across Canada, where 21,201 patients were randomized to either standard-volume or small-volume tubes for collecting blood samples. During the course of the study, each site switched to the small-volume collection tubes.
“We also showed there were no negative effects on lab testing, and by that we measured the sufficiency of the specimens,” Dr. Siegal added. “We were able to show that there wasn’t a problem with the amount of blood that was available for the tests to be done.”
The samples were collected from February 2019 through January 2021, through the period of COVID-19 restrictions. Dr. Siegal explained that 6,210 patients admitted early in the COVID-19 pandemic were excluded from the primary analysis, but were included in secondary analyses.
Study results
While the study found no significant difference in RBC units per patient per ICU stage – a relative risk of .91 (95% confidence interval, 0.79-1.05; P = .19), it did find an absolute reduction of 7.24 RBC units/100 patients per ICU stay.
Findings from the secondary analyses, which included 27,411 patients, were:
- A 12% reduction in RBC units per patient per ICU stay after switching from standard-volume to small-volume tubes (RR, 0.88; 95% CI, 0.77-1; P = .04).
- An absolute reduction of 9.84 RBC units/100 patients per ICU stay (95% CI, 0.24-20.76).
In the primary analysis population, the median transfusion-adjusted hemoglobin was not statistically different between the standard- and small-volume collection tube groups, with an average difference of 0.1 g/dL (95% CI, –0.04 to .23), but it was lower in the secondary population, with a mean difference of .17 g/dL (95% CI, 0.05-0.29).
“Those patients that we analyzed in the secondary analysis population received about 36,000 units of blood, just in 25 ICU units in Canada in less than 2 years,” Dr. Siegal said. “If we saved 10 units per 100 patients, that’s 1,500 units of blood. That really speaks to a small effect at the individual patient level but really potential for widespread effect. We are now in a period of blood product shortage not only in Canada but worldwide.”
First clinical trial for small tubes
Dr. Siegal noted this was the first clinical trial to compare standard- and small-volume blood collection tools, “and also to show there is both a benefit and a lack of harm,” Dr. Siegal said. “We thought that a randomized trial was the best way to move the needle. If we could design a trial of a large population of patients to show benefit and no harm, it would be a win, and that’s in fact what happened.”
She added, “The tubes essentially have the same cost, work the same, and go on the same equipment the same way the standard-volume tubes do, so it wasn’t a practice change for people in the hospital.”
The study also found an identical low rate of unusable specimens did not differ regardless of the type of collection tube: less than .03%.
Dr. Siegal said the study group is collaborating with hematology stakeholders in Canada, including Canadian Blood Services, which provides blood plasma to the country’s provincial and territorial health systems, and is reaching out to the American Society of Hematology.
“We’re going to target both hematologists and critical care providers and, even more broadly than the critical care community, hospitals, because anemia is big problem in hospitals,” Dr. Siegal said. “I think we can think about this more broadly.”
The study received funding from the Hamilton Academic Health Sciences Organization. Dr. Siegal disclosed relationships with Bristol-Myers Squibb-Pfizer, AstraZeneca and Roche.
A large Canadian clinical trial has found that using small-volume tubes to collect blood samples for laboratory testing of intensive care unit patients can reduce blood transfusions without affecting lab results.
“We showed in a large pragmatic cluster trial that automatically collect less blood for laboratory testing reduced red blood cell transfusions by about 10 units of red blood cells per 100 patients in the ICU,” lead study author Deborah M. Siegal, MD, associate professor at the University of Ottawa and scientist at the Ottawa Hospital Research Institute, said.
The study was coordinated by the Population Health Research Institute, an affiliate of McMaster University in Hamilton (Ont.) Health Sciences, where Dr. Siegal worked before moving to Ottawa.
The STRATUS randomized clinical trial, published in JAMA, involved 25 adult medical-surgical ICUs across Canada, where 21,201 patients were randomized to either standard-volume or small-volume tubes for collecting blood samples. During the course of the study, each site switched to the small-volume collection tubes.
“We also showed there were no negative effects on lab testing, and by that we measured the sufficiency of the specimens,” Dr. Siegal added. “We were able to show that there wasn’t a problem with the amount of blood that was available for the tests to be done.”
The samples were collected from February 2019 through January 2021, through the period of COVID-19 restrictions. Dr. Siegal explained that 6,210 patients admitted early in the COVID-19 pandemic were excluded from the primary analysis, but were included in secondary analyses.
Study results
While the study found no significant difference in RBC units per patient per ICU stage – a relative risk of .91 (95% confidence interval, 0.79-1.05; P = .19), it did find an absolute reduction of 7.24 RBC units/100 patients per ICU stay.
Findings from the secondary analyses, which included 27,411 patients, were:
- A 12% reduction in RBC units per patient per ICU stay after switching from standard-volume to small-volume tubes (RR, 0.88; 95% CI, 0.77-1; P = .04).
- An absolute reduction of 9.84 RBC units/100 patients per ICU stay (95% CI, 0.24-20.76).
In the primary analysis population, the median transfusion-adjusted hemoglobin was not statistically different between the standard- and small-volume collection tube groups, with an average difference of 0.1 g/dL (95% CI, –0.04 to .23), but it was lower in the secondary population, with a mean difference of .17 g/dL (95% CI, 0.05-0.29).
“Those patients that we analyzed in the secondary analysis population received about 36,000 units of blood, just in 25 ICU units in Canada in less than 2 years,” Dr. Siegal said. “If we saved 10 units per 100 patients, that’s 1,500 units of blood. That really speaks to a small effect at the individual patient level but really potential for widespread effect. We are now in a period of blood product shortage not only in Canada but worldwide.”
First clinical trial for small tubes
Dr. Siegal noted this was the first clinical trial to compare standard- and small-volume blood collection tools, “and also to show there is both a benefit and a lack of harm,” Dr. Siegal said. “We thought that a randomized trial was the best way to move the needle. If we could design a trial of a large population of patients to show benefit and no harm, it would be a win, and that’s in fact what happened.”
She added, “The tubes essentially have the same cost, work the same, and go on the same equipment the same way the standard-volume tubes do, so it wasn’t a practice change for people in the hospital.”
The study also found an identical low rate of unusable specimens did not differ regardless of the type of collection tube: less than .03%.
Dr. Siegal said the study group is collaborating with hematology stakeholders in Canada, including Canadian Blood Services, which provides blood plasma to the country’s provincial and territorial health systems, and is reaching out to the American Society of Hematology.
“We’re going to target both hematologists and critical care providers and, even more broadly than the critical care community, hospitals, because anemia is big problem in hospitals,” Dr. Siegal said. “I think we can think about this more broadly.”
The study received funding from the Hamilton Academic Health Sciences Organization. Dr. Siegal disclosed relationships with Bristol-Myers Squibb-Pfizer, AstraZeneca and Roche.
A large Canadian clinical trial has found that using small-volume tubes to collect blood samples for laboratory testing of intensive care unit patients can reduce blood transfusions without affecting lab results.
“We showed in a large pragmatic cluster trial that automatically collect less blood for laboratory testing reduced red blood cell transfusions by about 10 units of red blood cells per 100 patients in the ICU,” lead study author Deborah M. Siegal, MD, associate professor at the University of Ottawa and scientist at the Ottawa Hospital Research Institute, said.
The study was coordinated by the Population Health Research Institute, an affiliate of McMaster University in Hamilton (Ont.) Health Sciences, where Dr. Siegal worked before moving to Ottawa.
The STRATUS randomized clinical trial, published in JAMA, involved 25 adult medical-surgical ICUs across Canada, where 21,201 patients were randomized to either standard-volume or small-volume tubes for collecting blood samples. During the course of the study, each site switched to the small-volume collection tubes.
“We also showed there were no negative effects on lab testing, and by that we measured the sufficiency of the specimens,” Dr. Siegal added. “We were able to show that there wasn’t a problem with the amount of blood that was available for the tests to be done.”
The samples were collected from February 2019 through January 2021, through the period of COVID-19 restrictions. Dr. Siegal explained that 6,210 patients admitted early in the COVID-19 pandemic were excluded from the primary analysis, but were included in secondary analyses.
Study results
While the study found no significant difference in RBC units per patient per ICU stage – a relative risk of .91 (95% confidence interval, 0.79-1.05; P = .19), it did find an absolute reduction of 7.24 RBC units/100 patients per ICU stay.
Findings from the secondary analyses, which included 27,411 patients, were:
- A 12% reduction in RBC units per patient per ICU stay after switching from standard-volume to small-volume tubes (RR, 0.88; 95% CI, 0.77-1; P = .04).
- An absolute reduction of 9.84 RBC units/100 patients per ICU stay (95% CI, 0.24-20.76).
In the primary analysis population, the median transfusion-adjusted hemoglobin was not statistically different between the standard- and small-volume collection tube groups, with an average difference of 0.1 g/dL (95% CI, –0.04 to .23), but it was lower in the secondary population, with a mean difference of .17 g/dL (95% CI, 0.05-0.29).
“Those patients that we analyzed in the secondary analysis population received about 36,000 units of blood, just in 25 ICU units in Canada in less than 2 years,” Dr. Siegal said. “If we saved 10 units per 100 patients, that’s 1,500 units of blood. That really speaks to a small effect at the individual patient level but really potential for widespread effect. We are now in a period of blood product shortage not only in Canada but worldwide.”
First clinical trial for small tubes
Dr. Siegal noted this was the first clinical trial to compare standard- and small-volume blood collection tools, “and also to show there is both a benefit and a lack of harm,” Dr. Siegal said. “We thought that a randomized trial was the best way to move the needle. If we could design a trial of a large population of patients to show benefit and no harm, it would be a win, and that’s in fact what happened.”
She added, “The tubes essentially have the same cost, work the same, and go on the same equipment the same way the standard-volume tubes do, so it wasn’t a practice change for people in the hospital.”
The study also found an identical low rate of unusable specimens did not differ regardless of the type of collection tube: less than .03%.
Dr. Siegal said the study group is collaborating with hematology stakeholders in Canada, including Canadian Blood Services, which provides blood plasma to the country’s provincial and territorial health systems, and is reaching out to the American Society of Hematology.
“We’re going to target both hematologists and critical care providers and, even more broadly than the critical care community, hospitals, because anemia is big problem in hospitals,” Dr. Siegal said. “I think we can think about this more broadly.”
The study received funding from the Hamilton Academic Health Sciences Organization. Dr. Siegal disclosed relationships with Bristol-Myers Squibb-Pfizer, AstraZeneca and Roche.
FROM JAMA
Sedative use in older adults after critical illness
Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.
While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)
The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).
The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.
Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.
In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.
Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.
While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)
The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).
The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.
Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.
In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.
Modifications to medication regimens may include stopping home medications for chronic conditions, dose adjustments for altered organ function, or initiating new treatments for acute illness(es). Common examples of changes to a critically ill patient’s medication regimen are stopping a chronic antihypertensive drug in the setting of shock, holding an oral medication that cannot be crushed or administered through a feeding tube, and initiating sedatives and analgesics to support invasive mechanical ventilation. Medication regimens are especially vulnerable to errors and omissions at transition points (i.e., ICU to ward transfers and home discharge). As critical illness resolves and patients transition to different care teams, the hospital discharge medication regimen may differ from the preadmission list with the omission of prehospital medications and/or the continuation of acute medications no longer needed without thorough medication review and reconciliation.
While admitted to ICU, many critically ill patients – particularly those who are mechanically ventilated – receive intravenous or enteral sedatives such as benzodiazepines and antipsychotics. Sedatives are prescribed to more than two-thirds of critically ill patients for disturbing symptoms of agitation, delirium, anxiety, and insomnia and to facilitate invasive procedures (Burry LD, et al. J Crit Care. 2017;42:268). Current sedation practice guidelines endorse the use of sedatives when indicated for the shortest duration possible, given the known associated serious short- and long-term adverse drug events (Devlin JW, et al. Crit Care Med. 2018;46[9]:e825). Previous research has demonstrated that benzodiazepines initiated in-hospital are often continued on discharge for older adults and that patients from the ICU are at greater risk of benzodiazepine continuation than patients hospitalized without an ICU admission (Scales DC, et al. J Gen Intern Med. 2016;31[2]:196; Bell C, et al. J Gen Intern Med. 2007;22[7]:1024). This is particularly concerning for older adults as sedatives have been associated with serious adverse events in community-dwelling older adults, including falls and cognitive impairment (American Geriatrics Society. J Am Geriatr Soc. 2015;63[11]:2227)
The cohort of patients included all adults aged 66 years or more, who were discharged alive from the hospital and who were sedative-naive prior to hospitalization. Sedative-naive status was defined as no sedative prescription filled for any class, dose, or duration in the 180 days before hospital admission. The proportion of ICU survivors who filled a sedative prescription within 1 week of hospital discharge was the primary outcome. The secondary outcomes were the proportion of patients that filled each sedative class (e.g., antipsychotic, benzodiazepine, nonbenzodiazepine sedative) within 1 week of hospital discharge and persistent sedative prescription (additional prescriptions filled within 6 months after discharge).
The cohort included 250,428 sedative-naive older adults. The mean age was 75.8 years, 61.0% were male, 26.3% received invasive mechanical ventilation, and 14.8% had sepsis. In total, 6.1% (n=15,277) of patients filled a sedative prescription within 1 week of discharge; 57.7% (n = 8824) filled a benzodiazepine, 18.0% (n = 2749) filled a non-benzodiazepine sedative, 17.9% (n = 2745) filled an antipsychotic, and 6.2% (n = 959) filled more than 1 sedative drug class. Most patients filled prescriptions on the day of discharge (median 0 days (interquartile range (IQR) 0-3). The study found considerable variation in the primary outcome across the 153 hospitals: 2.1% (95% confidence interval [CI] 1.2% to 2.8%) to 44.0% (95% CI 3.0% to –57.8%) filled a sedative prescription within a week of hospital discharge. The factors strongly associated with an increased odds of a sedative prescription filled within a week of discharge included: discharge to long-term care (adjusted OR (aOR) 4.00, 95% CI 3.72 to 4.31), receipt of inpatient geriatric (aOR 1.95, 95% CI 1.80 to 2.10) or psychiatry consultation (aOR 2.76, 95% CI 2.62, 2.91), mechanical ventilation (aOR 1.59, 95% CI 1.53 to 1.66), and admitted ≥ 7 days to the ICU (aOR 1.50, 95% CI 1.42 to 1.58). Among hospital factors, a community hospital (vs academic) (aOR 1.40, 95% CI 1.16 to 1.70) and rural location (vs urban) (aOR 1.67, 95% CI 1.36 to 2.05) were also associated with new sedative prescriptions. Even after adjusting for patient and site characteristics, there was considerable remaining variability between sites quantified by the median odds ratio (aMOR) of 1.43. By drug class, there were similar findings with the exception of different associations for sex and frailty. For benzodiazepine prescriptions, female sex was associated with increased odds of a prescription (aOR 1.13, 95% CI 1.08 to 1.18), while frailty was inversely associated (aOR 0.82, 95% CI 0.75 to 0.89). The opposite associations were identified for antipsychotics: female sex (aOR 0.75, 95% CI 0.69 to 0.81) and frailty (aOR 1.41, 95% CI 1.28 to 1.55). No associations were identified for sex and frailty and non-benzodiazepine sedative prescriptions.
Persistent sedative prescription was common as 55% met the definition of persistence, filling a median of 2 prescriptions (IQR 1,3) in the 6 months after hospital discharge. The factors associated with persistent sedative prescriptions were similar to those identified above except female sex was associated with persistent sedative prescription (sHR 1.07, 95% CI 1.02 to 1.13). Those who filled an antipsychotic prescription (sHR 1.45, 95% CI 1.35 to 1.56), a non-benzodiazepine sedative prescription (sHR 1.44, 955 CI 1.34 to 1.53), or prescriptions for more than 1 sedative class filled (sHR 2.16, 95% CI 1.97 to 2.37) were more likely to fill persistent prescriptions compared with those who filled a prescription for a benzodiazepine alone as their first sedative.
In summary, 1 in 15 sedative-naive older adults filled a sedative prescription within a week of hospital discharge following a critical illness, and many continued to fill sedative prescriptions in the next 6 months. We were able to identify factors associated with new sedative prescriptions that could be targeted for stewardship programs or quality improvement projects that focus on medication safety and reconciliation. Medication stewardship and reconciliation processes have been broadly studied in many patient care settings but not the ICU. There is still much to determine regarding de-escalating and discontinuing sedatives as critical illness resolves and patients are liberated from intensive clinical interventions as well as the consequences of sedative exposure after hospital discharge for this population.
Dr. Burry is with the Departments of Pharmacy and Medicine, Sinai Health; Leslie Dan Faculty of Pharmacy and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Canada. Dr. Williamson is with the Faculté de Pharmacie, Université de Montréal; Pharmacy Département, Hôpital du Sacré-Cœur de Montréal; and Research center, CIUSSS du Nord-de-l’Île-de-Montréal, Canada.
Piperacillin-tazobactam poses no renal risk in adults with sepsis
TOPLINE:
METHODOLOGY:
The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.
The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.
Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).
The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
TAKEAWAY:
The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).
The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).
Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
IN PRACTICE:
In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”
SOURCE:
The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.
LIMITATIONS:
The study was conducted at a single academic center, which may limit the generalizability of findings.
Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
DISCLOSURES:
The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.
The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.
Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).
The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
TAKEAWAY:
The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).
The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).
Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
IN PRACTICE:
In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”
SOURCE:
The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.
LIMITATIONS:
The study was conducted at a single academic center, which may limit the generalizability of findings.
Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
DISCLOSURES:
The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
The coadministration of piperacillin-tazobactam and vancomycin may raise the risk for AKI, according to a warning from the Food and Drug Administration.
The ACORN trial included 2,511 adults presenting to emergency department or intensive care unit with suspected infection.
Within 12 hours of presentation, these individuals were prescribed either cefepime (n = 1,214) or piperacillin-tazobactam (n = 1,297).
The primary outcome was the risk for the highest stage of AKI or death within 14 days of randomization.
TAKEAWAY:
The highest stage of AKI or death within 14 days did not differ significantly between the cefepime and piperacillin-tazobactam groups (odds ratio, 0.95; P = .56).
The incidence of major adverse kidney events by day 14 was not significantly different between the two groups (absolute risk difference, 1.4%; 95% confidence interval, −1.0% to 3.8%).
Patients in the cefepime versus piperacillin-tazobactam group had fewer days alive and free of delirium and coma within 14 days (OR, 0.79; 95% CI, 0.65-0.95).
IN PRACTICE:
In an accompanying editorial, Steven Y. C. Tong, department of infectious diseases, University of Melbourne, and colleagues wrote: “Because institutions must make decisions about which antibiotics to position on medical wards for rapid administration in patients meeting sepsis criteria, these data should offer solace that if the choice is made to use piperacillin-tazobactam, there is not an increased risk of AKI.”
SOURCE:
The study was led by Edward T. Qian, MD, of Vanderbilt University Medical Center, Nashville, Tenn. It was published online in JAMA with an accompanying editorial.
LIMITATIONS:
The study was conducted at a single academic center, which may limit the generalizability of findings.
Both patients and clinicians were not blinded to group assignment, which may have influenced clinical assessments like Richmond Agitation-Sedation Scale and CAM-ICU or the frequency of laboratory measurements like creatinine.
DISCLOSURES:
The project was supported by the Vanderbilt Institute for Clinical and Translational Research and several other sources, including grants from the National Center for Advancing Translational Sciences. Some authors declared receiving travel grant, personal fees, honoraria, and unrelated research support from various sources.
A version of this article appeared on Medscape.com.
Pulmonary hypertension increases ARDS mortality risk
HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.
Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of . In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).
“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.
He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
National database
PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.
To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.
They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.
The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.
In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.
In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.
Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.
The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
Potential to inform practice
A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.
“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.
“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.
The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.
Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of . In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).
“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.
He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
National database
PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.
To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.
They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.
The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.
In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.
In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.
Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.
The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
Potential to inform practice
A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.
“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.
“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.
The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
HONOLULU – Patients with acute respiratory distress syndrome (ARDS) and coexisting pulmonary hypertension (PH) are significantly more likely to have longer and more costly hospital stays and to die in-hospital than patients with ARDS without PH, results of a retrospective study suggest.
Among more than 156,000 hospitalized patients with ARDS, 16.8% of whom also had a diagnosis of PH, the presence of . In addition, the presence of PH was associated with nearly $20,000 of higher hospital expenditures, reported Kaushik Kumar, MBBS, at the annual meeting of the American College of Chest Physicians (CHEST).
“Clinicians should be vigilant in identifying and managing pulmonary hypertension in ARDS patients,” Dr. Kumar, a resident in internal medicine at Medstar Health, Baltimore, said in an oral abstract presentation.
He added that PH has the potential to serve as an indicator of disease severity for patients with ARDS.
National database
PH is a frequent complication of ARDS, likely related to a combination of pulmonary vasoconstriction, thromboembolism, and interstitial edema, he said.
To test their hypothesis that the presence of PH in patients with ARDS is associated with worse outcomes, Dr. Kumar and colleagues drew on the National Inpatient Sample database for information on adults aged 18 years and older who had been diagnosed with ARDS with or without PH.
They identified a total of 156,687 patients of whom 26,324 (16.8%) also had been diagnosed with PH. Among the cohort with PH, there were higher proportions of older patients, women, and patients with multiple comorbidities.
The in-hospital mortality rate was 36.8% among patients with PH, compared with 24.6% among those without. The mean length of stay was also longer among patients with PH, at 12 days versus 10 days.
In an unadjusted analysis, mean total hospital charges for patients with ARDS and PH were $210,165, versus $160,683 for patients with ARDS who did not have PH.
In an analysis in which the investigators controlled for age, sex, index admission length of stay, insurance status, and comorbidities, in-hospital mortality for patients with PH remained significantly higher, with an odds ratio of 1.52 (P < .001). PH was also significantly associated with longer length of stay (odds ratio, 1.37; P < .001) and higher total hospital costs, with a mean difference of $19,406.
Dr. Kumar said that the findings underscore the importance of a tailored approach to managing patients with ARDS, especially in the presence of PH.
The investigators plan further studies to assess the role of PH-targeted therapies, to examine the role of sepsis and right ventricular failure and to explore the long-term impact of PH among ARDS survivors, including effects with respect to pulmonary function, quality of life, and long-term morbidity.
Potential to inform practice
A pulmonologist who was not involved in the study said in an interview that the findings of the trial suggest that PH may have a greater influence on mortality than is currently understood and that further investigations into this association could change practice in the future.
“I think it would be very important for us to understand if that is going to change our outlook on how ARDS is managed. It’s possible that some of the interventions that we give people who don’t have pulmonary hypertension, for example, increasing the airway pressure in order to minimize oxygenation, may have a detrimental effect on the pulmonary vasculature,” said Timothy Morris, MD, medical director of the pulmonary and exercise lab and professor of medicine at the University of California, San Diego.
“I think it’s a little bit premature to say that this should guide management now, but it’s certainly an interesting question that may end up changing practice in the future,” said Dr. Morris, who was moderator of the session in which Dr. Kumar presented the data.
The study was supported by the Agency for Healthcare Research and Quality and Medstar Health Research Institute. Dr. Kumar and Dr. Morris have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
AT CHEST 2023
Now we have MERCY
Critical Care Network
Sepsis/Shock Section
Beta-lactam antibiotics, including penicillin, carbapenems, and cephalosporins, exhibit time-dependent bacterial eradication. Prolonged infusions are thought to enhance the duration of effective bactericidal antibiotic exposure, decreasing the emergence of drug resistance due to reduced bacterial regrowth between doses – which may lead to cost savings by reducing drug acquisition costs and shortening hospital stays (Lodise TP Jr, et al. Clin Infect Dis. 2007;44[3]:357-63).
The best evidence for these benefits comes from observational studies and meta-analyses. The Defining Antibiotic Levels in Intensive Care Unit Patients (DALI) study emphasized the correlation between achieving target concentrations of beta-lactam antibiotics in critically ill patients and positive clinical outcomes for bloodstream infections but not for lung or intra-abdominal infections (Roberts JA, et al. Clin Infect Dis. 2014;58[8]:1072-83). A meta-analysis of 29 studies suggested that prolonged infusion of piperacillin-tazobactam was associated with a mortality benefit compared with intermittent infusions, but prolonged infusions of cephalosporins or carbapenems resulted in comparable outcomes without mortality benefit (Teo J, et al. Int J Antimicrob Agents. 2014;43[5]:403-11).
MERCY was a multinational, randomized controlled trial investigating the efficacy of continuous vs intermittent administration of meropenem in critically ill patients with sepsis. The primary outcome, a composite of mortality and emergence of resistant bacteria at day 28, showed no significant difference between continuous and intermittent administration (47% vs. 49%). Secondary outcomes and adverse events also did not display significant differences, suggesting that continuous meropenem did not improve outcomes compared with intermittent administration (Monti G, et al. JAMA. 2023;330[2]:141-51).
MERCY adds to the existing body of evidence suggesting that prolonged and intermittent infusion strategies for meropenem are at least equivalent in efficacy. Therefore, the strategy chosen can depend on other individualized factors.
The views expressed are those of the authors and do not reflect the official policy or position of the U.S. Navy, Department of Defense, or the US Government.
Meredith L. Olsen, MD, Section Member-at-Large
Casey Cable, MD, FCCP, Section Member-at-Large
Kathryn Pendleton, MD, FCCP, Section Vice-Chair
Critical Care Network
Sepsis/Shock Section
Beta-lactam antibiotics, including penicillin, carbapenems, and cephalosporins, exhibit time-dependent bacterial eradication. Prolonged infusions are thought to enhance the duration of effective bactericidal antibiotic exposure, decreasing the emergence of drug resistance due to reduced bacterial regrowth between doses – which may lead to cost savings by reducing drug acquisition costs and shortening hospital stays (Lodise TP Jr, et al. Clin Infect Dis. 2007;44[3]:357-63).
The best evidence for these benefits comes from observational studies and meta-analyses. The Defining Antibiotic Levels in Intensive Care Unit Patients (DALI) study emphasized the correlation between achieving target concentrations of beta-lactam antibiotics in critically ill patients and positive clinical outcomes for bloodstream infections but not for lung or intra-abdominal infections (Roberts JA, et al. Clin Infect Dis. 2014;58[8]:1072-83). A meta-analysis of 29 studies suggested that prolonged infusion of piperacillin-tazobactam was associated with a mortality benefit compared with intermittent infusions, but prolonged infusions of cephalosporins or carbapenems resulted in comparable outcomes without mortality benefit (Teo J, et al. Int J Antimicrob Agents. 2014;43[5]:403-11).
MERCY was a multinational, randomized controlled trial investigating the efficacy of continuous vs intermittent administration of meropenem in critically ill patients with sepsis. The primary outcome, a composite of mortality and emergence of resistant bacteria at day 28, showed no significant difference between continuous and intermittent administration (47% vs. 49%). Secondary outcomes and adverse events also did not display significant differences, suggesting that continuous meropenem did not improve outcomes compared with intermittent administration (Monti G, et al. JAMA. 2023;330[2]:141-51).
MERCY adds to the existing body of evidence suggesting that prolonged and intermittent infusion strategies for meropenem are at least equivalent in efficacy. Therefore, the strategy chosen can depend on other individualized factors.
The views expressed are those of the authors and do not reflect the official policy or position of the U.S. Navy, Department of Defense, or the US Government.
Meredith L. Olsen, MD, Section Member-at-Large
Casey Cable, MD, FCCP, Section Member-at-Large
Kathryn Pendleton, MD, FCCP, Section Vice-Chair
Critical Care Network
Sepsis/Shock Section
Beta-lactam antibiotics, including penicillin, carbapenems, and cephalosporins, exhibit time-dependent bacterial eradication. Prolonged infusions are thought to enhance the duration of effective bactericidal antibiotic exposure, decreasing the emergence of drug resistance due to reduced bacterial regrowth between doses – which may lead to cost savings by reducing drug acquisition costs and shortening hospital stays (Lodise TP Jr, et al. Clin Infect Dis. 2007;44[3]:357-63).
The best evidence for these benefits comes from observational studies and meta-analyses. The Defining Antibiotic Levels in Intensive Care Unit Patients (DALI) study emphasized the correlation between achieving target concentrations of beta-lactam antibiotics in critically ill patients and positive clinical outcomes for bloodstream infections but not for lung or intra-abdominal infections (Roberts JA, et al. Clin Infect Dis. 2014;58[8]:1072-83). A meta-analysis of 29 studies suggested that prolonged infusion of piperacillin-tazobactam was associated with a mortality benefit compared with intermittent infusions, but prolonged infusions of cephalosporins or carbapenems resulted in comparable outcomes without mortality benefit (Teo J, et al. Int J Antimicrob Agents. 2014;43[5]:403-11).
MERCY was a multinational, randomized controlled trial investigating the efficacy of continuous vs intermittent administration of meropenem in critically ill patients with sepsis. The primary outcome, a composite of mortality and emergence of resistant bacteria at day 28, showed no significant difference between continuous and intermittent administration (47% vs. 49%). Secondary outcomes and adverse events also did not display significant differences, suggesting that continuous meropenem did not improve outcomes compared with intermittent administration (Monti G, et al. JAMA. 2023;330[2]:141-51).
MERCY adds to the existing body of evidence suggesting that prolonged and intermittent infusion strategies for meropenem are at least equivalent in efficacy. Therefore, the strategy chosen can depend on other individualized factors.
The views expressed are those of the authors and do not reflect the official policy or position of the U.S. Navy, Department of Defense, or the US Government.
Meredith L. Olsen, MD, Section Member-at-Large
Casey Cable, MD, FCCP, Section Member-at-Large
Kathryn Pendleton, MD, FCCP, Section Vice-Chair
New guidelines for determining brain death released
The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.
As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.
But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.
Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.
“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”
The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
Four years in the making
Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.
A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.
The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.
The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.
In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
A uniform set of guidelines?
The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.
“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.
The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.
There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.
“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.
Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.
Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.
“But this attempts to unify things at the U.S. level, which is very important,” he said.
Permanent vs. irreversible
Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.
The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.
He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.
However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.
The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”
Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.
The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.
“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.
Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.
“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”
The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.
As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.
But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.
Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.
“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”
The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
Four years in the making
Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.
A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.
The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.
The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.
In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
A uniform set of guidelines?
The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.
“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.
The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.
There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.
“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.
Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.
Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.
“But this attempts to unify things at the U.S. level, which is very important,” he said.
Permanent vs. irreversible
Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.
The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.
He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.
However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.
The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”
Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.
The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.
“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.
Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.
“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”
The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The consensus practice guideline on brain death, also known as death by neurologic criteria (BD/DNC), was developed by a panel of 20 experts from different specialties, institutions, and medical societies.
As with previous guidelines, the updated version stipulates that brain death should be declared when a patient with a known cause of catastrophic brain injury has permanent loss of function of the brain, including the brain stem, which results in coma, brain stem areflexia, and apnea in the setting of an adequate stimulus.
But the updated version also clarifies questions on neurological examinations and apnea testing and offers new guidance on pre-evaluation targets for blood pressure and body temperature and evaluating brain death in patients who are pregnant, are on extracorporeal membrane oxygenation, or have an injury to the base of the brain.
Also, for the first time, the guidance clarifies that clinicians don’t need to obtain consent before performing a brain death evaluation, unless institutional policy, state laws, or regulations stipulate otherwise.
“The 2023 guidelines will be considered the standard of care in the U.S.,” lead author David M. Greer, MD, chair and chief of neurology, Boston University, and chief of neurology, Boston Medical Center, said in an interview. “Each hospital in the U.S. is responsible for its own policy for BD/DNC determination, and our hope is that they will quickly revise their policies in accordance with this new national standard.”
The guidelines, which are accompanied by a three-page checklist and a free digital app, were published online in Neurology.
Four years in the making
Work on the 85 recommendations in the new report began more than 4 years ago as a collaborative effort by the American Academy of Neurology, the American Academy of Pediatrics, the Child Neurology Society, and the Society of Critical Care Medicine.
A lack of high-quality evidence on brain death determination led panelists to devise an evidence-informed formal consensus process to develop the guidelines, which involved three rounds of anonymous voting on each recommendation and the rationales behind them.
The strength of each recommendation was based on the level of consensus reached through voting, with Level A denoting a recommendation that “must” be followed, Level B one that “should” be followed, and Level C one that “may” be followed.
The majority of recommendations received an A or B rating. Only one recommendation, about whether a second clinical exam is needed in adults, garnered a C rating.
In children, the guidelines recommend that clinicians must perform two clinical examinations and two apnea tests 12 hours apart. In adults, only one exam is required. Both of those recommendations were rated Level A. A recommendation for a second exam in adults received the single Level C rating.
A uniform set of guidelines?
The new guidelines replace adult practice guidance published by AAN in 2010 and guideline for infants and children released in 2011 by AAP, CNS, and SCCM, and for the first time combine brain death guidelines for adult and pediatric patients into one document.
“It is important for clinicians to review the new guideline carefully and ensure their hospital brain death guidelines are updated to be consistent with the new guideline in order to prevent inaccurate determinations of death,” guidelines coauthor Ariane Lewis, MD, NYU Langone Health, New York, said in an interview.
The 1981 Uniform Determination of Death Act (UDDA) is the legal foundation for the declaration of BD/DNC in the United States, but it only stipulates that brain death determination must be made in accordance with accepted medical standards.
There is no single national standard, and states and hospitals are free to adopt their own, which many have done. One goal of the new guidelines was to create a uniform set of guidelines that all institutions follow.
“This is a step toward having a set of guidelines that are accepted by most of the societies and clinical specialties involved in this sort of diagnosis,” that could lead to a national-level policy, Fernando Goldenberg, MD, professor of neurology and director of neuroscience critical care, University of Chicago Medicine, said in an interview.
Dr. Goldenberg was not part of the panel that developed the updated guidelines, but was a coauthor of a consensus statement from the World Brain Death Project in 2020.
Developing a singular global guideline for brain death determination is unlikely, Dr. Goldenberg said. Policies vary widely across the world, and some countries don’t even recognize brain death.
“But this attempts to unify things at the U.S. level, which is very important,” he said.
Permanent vs. irreversible
Dr. Goldenberg said that combining adult and pediatric guidelines into one document will be very helpful for clinicians like him who treat patients from age 16 years and up.
The expanded guidance on apnea testing, recommendations on specific ancillary tests to use or avoid, and inclusion of language stipulating that prior consent is not needed to perform a brain death evaluation are also useful.
He also noted that the section on credentialing and training of clinicians who perform BD/DNC evaluations recognizes advanced practice providers, the first time he recalls seeing these professionals included in brain death guidelines.
However, the panel’s decision to use the term “permanent” to describe loss of brain function instead of “irreversible” gave Dr. Goldenberg pause.
The UDDA provides that an individual is declared legally dead when “circulatory and respiratory functions irreversibly stop; or all functions of the entire brain, including the brain stem, irreversibly stop.”
Earlier in October, the American College of Physicians released a position paper on cardiorespiratory death determination that called for a revision of the UDDA language.
The ACP suggested that “irreversibly” be replaced with “permanently” with regard to the cessation of circulatory and respiratory functions, but that “irreversible” be kept in the description of brain death.
“Permanent means that there is damage that is potentially reversible and irreversible means that the damage is so profound, it cannot be reversed even if an attempt to do so is performed,” Dr. Goldenberg said.
Even though the World Brain Death Project, on which he worked, also used “permanent” to describe brain function loss, Dr. Goldenberg said he aligns with ACP’s position.
“The understanding of brain death is that the damage is so profound, it is irreversible, even if you were to try,” he said. “Therefore, I think that the most appropriate term for brain death should be irreversible as opposed to permanent.”
The report was funded by the American Academy of Neurology. Dr. Greer has received travel funding from Boston University; serves as editor-in-chief for Seminars in Neurology; receives publishing royalties for 50 Studies Every Neurologist Should Know and Successful Leadership in Academic Medicine; has received honoraria from AAN; has received research funding from Becton, Dickinson, and Company; and has served as expert witness in legal proceedings. Dr. Lewis has received honoraria from AAN and Neurodiem, serves as Neurology deputy editor of disputes and debates, and serves as deputy editor of seminars in Neurology. Dr. Goldenberg reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Paxlovid tied to benefits in high-risk patients with COVID
In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.
“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”
The study was published online in JAMA Network Open.
Who benefits?
The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.
Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.
The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.
Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.
The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”
The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.
British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.
Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”
The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
‘Signal toward benefit’
Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.
“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”
Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.
“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”
The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.
A version of this article appeared on Medscape.com.
In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.
“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”
The study was published online in JAMA Network Open.
Who benefits?
The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.
Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.
The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.
Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.
The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”
The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.
British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.
Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”
The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
‘Signal toward benefit’
Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.
“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”
Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.
“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”
The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.
A version of this article appeared on Medscape.com.
In a cohort study from British Columbia that included nearly 7,000 patients with COVID-19, nirmatrelvir-ritonavir was associated with a 2.5% reduction in risk for death or emergency hospitalization in clinically extremely vulnerable (CEV) patients who were severely immunocompromised. No significant benefit was observed in patients who were not immunocompromised.
“This finding could help substantially limit unnecessary use of nirmatrelvir and ritonavir in older, otherwise healthy individuals,” lead author Colin R. Dormuth, ScD, associate professor of anesthesiology, pharmacology, and therapeutics at the University of British Columbia, Vancouver, told this news organization. “Another finding that was surprising and might help place the role of nirmatrelvir and ritonavir in context is that even in severely immunocompromised individuals who did not take [the drug], the risk of death or hospitalization with COVID-19 was less than 4% in our study population.”
The study was published online in JAMA Network Open.
Who benefits?
The investigators analyzed medical records for 6,866 patients in British Columbia (median age, 70 years; 57% women) who presented between Feb. 1, 2022, and Feb. 3, 2023. Eligible patients belonged to one of four higher-risk groups who received priority for COVID-19 vaccination.
Two groups included CEV patients who were severely (CEV1) or moderately (CEV2) immunocompromised. The CEV3 group was not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group included higher-risk patients who were not in one of the other groups, such as unvaccinated patients older than age 70 years.
The investigators matched treated patients to untreated patients in the same vulnerability group according to age, sex, and month of infection. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days.
Treatment with nirmatrelvir-ritonavir was associated with statistically significant relative reductions in the primary outcome, compared with no treatment, for patients in the CEV1 (risk difference, −2.5%) and CEV2 (RD, −1.7%) groups. In the CEV3 group, the RD of −1.3% was not statistically significant. In the EXEL group, treatment was associated with a higher risk for the primary outcome (RD, 1.0%), but the result was not statistically significant.
The results were “robust across sex and older vs. younger age,” the authors note. “No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.”
The combination of nirmatrelvir-ritonavir was approved for use in Canada based on interim efficacy and safety data from the Evaluation of Inhibition for COVID-19 in High-Risk Patients (EPIC-HR) trial, said Dr. Dormuth.
British Columbia’s eligibility criteria for nirmatrelvir-ritonavir coverage differ substantially from the criteria for participants in the EPIC-HR trial, he noted. Those patients were unvaccinated, had no natural immunity from a previous COVID-19 infection, and were infected with COVID-19 variants that were different from those now circulating. The current study was prompted by the need to look at a broader population of individuals in British Columbia with varying risks of complications from COVID-19 infection.
Before the study, a common view was that patients aged 70 and older would benefit from the drug, said Dr. Dormuth. “Our study, which accounted for medical conditions related to an individual’s vulnerability to complications, showed that older age on its own was not a reason to use nirmatrelvir and ritonavir once relevant medical conditions were taken into consideration.”
The researchers are working on a study to identify with greater specificity which comorbid conditions are most associated with nirmatrelvir-ritonavir effectiveness, he added. “It could be that a relatively small number of conditions can be used to identify most individuals who would benefit from the drug.”
‘Signal toward benefit’
Commenting on the findings for this news organization, Abhijit Duggal, MD, vice chair of critical care at the Cleveland Clinic, who was not involved in this study, said, “I’m always very wary when we look at observational data and we start saying the effectiveness is not really as high as was seen in other studies. We are seeing an effect with all these studies that seems to be in the right direction.
“Having said that,” he added, “is the effect going to be potentially more in patients at higher risk? Absolutely. I think these postmarket studies are really showing that after vaccination, if someone does get infected, this is a secondary option available to us that can prevent progression of the disease, which would likely be more severe in immunocompromised patients.”
Dr. Duggal was a coinvestigator on a recent study of more than 68,000 patients that showed that nirmatrelvir-ritonavir or molnupiravir was associated with reductions in mortality and hospitalization in nonhospitalized patients infected with the Omicron variant, regardless of age, race and ethnicity, virus strain, vaccination status, previous infection status, or coexisting conditions.
“In all groups, there was a signal toward benefit,” said Dr. Duggal. “These studies tell us that these drugs do remain valid options. But their use needs to be discussed on a case-by-case basis with patients we feel are deteriorating or at a higher risk because of underlying disease processes.”
The study was supported by funding from the British Columbia Ministry of Health. Dr. Dormuth and Dr. Duggal report no relevant financial relationships.
A version of this article appeared on Medscape.com.
Addressing Physician Burnout in Pulmonology and Critical Care
- Moss M et al. Crit Care Med. 2016;44(7):1414-1421. doi:10.1097/CCM.000000000000188
- Medscape National Physician Burnout, Depression & Suicide Report 2019. Medscape. January 16, 2019. Accessed June 22, 2023. https://www.medscape.com/slideshow/2019-lifestyle-burnout-depression-6011056#1
- Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide. Medscape. January 15, 2020. Accessed June 22, 2023. https://www.medscape.com/slideshow/2020-lifestyle-burnout-6012460#1
- ‘Death by 1000 Cuts’: Medscape National Physician Burnout & Suicide Report 2021. Medscape. January 22, 2021. Accessed June 22, 2023. https://www.medscape.com/slideshow/2021-lifestyle-burnout-6013456#2
- Physician Burnout Report 2022: Stress, Anxiety, and Anger. Medscape. January 21, 2022. Accessed June 22, 2023. https://www.medscape.com/slideshow/2022-lifestyle-burnout-6014664#1
- ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023. Medscape. January 27, 2023. Accessed June 22, 2023. https://www.medscape.com/slideshow/2023-lifestyle-burnout-6016058#1
- Murthy VH. N Engl J Med. 2022;387(7):577-579. doi:10.1056/NEJMp2207252
- Vranas KC et al. Chest. 2021;160(5):1714-1728. doi:10.1016/j.chest.2021.05.041
- Kerlin MP et al. Ann Am Thorac Soc. 2022;19(2):329-331. doi:10.1513/AnnalsATS.202105-567RL
- Dean W et al. Fed Pract. 2019;36(9):400-402. PMID: 31571807
- Association of American Medical Colleges. The Complexities of Physician Supply and Demand: Projections from 2019 to 2034. June 2021. https://www.aamc.org/media/54681/download?attachment
- Medscape Pulmonologist Lifestyle, Happiness & Burnout Report 2023: Contentment Amid Stress. February 24, 2023. Accessed June 28, 2023. https://www.medscape.com/slideshow/2023-lifestyle-pulmonologist-6016092#1
- Medscape Intensivist Lifestyle, Happiness & Burnout Report 2023: Contentment Amid Stress. February 24, 2023. Accessed June 28, 2023. https://www.medscape.com/slideshow/2023-lifestyle-intensivist-6016072#1
- Moss M et al. Crit Care Med. 2016;44(7):1414-1421. doi:10.1097/CCM.000000000000188
- Medscape National Physician Burnout, Depression & Suicide Report 2019. Medscape. January 16, 2019. Accessed June 22, 2023. https://www.medscape.com/slideshow/2019-lifestyle-burnout-depression-6011056#1
- Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide. Medscape. January 15, 2020. Accessed June 22, 2023. https://www.medscape.com/slideshow/2020-lifestyle-burnout-6012460#1
- ‘Death by 1000 Cuts’: Medscape National Physician Burnout & Suicide Report 2021. Medscape. January 22, 2021. Accessed June 22, 2023. https://www.medscape.com/slideshow/2021-lifestyle-burnout-6013456#2
- Physician Burnout Report 2022: Stress, Anxiety, and Anger. Medscape. January 21, 2022. Accessed June 22, 2023. https://www.medscape.com/slideshow/2022-lifestyle-burnout-6014664#1
- ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023. Medscape. January 27, 2023. Accessed June 22, 2023. https://www.medscape.com/slideshow/2023-lifestyle-burnout-6016058#1
- Murthy VH. N Engl J Med. 2022;387(7):577-579. doi:10.1056/NEJMp2207252
- Vranas KC et al. Chest. 2021;160(5):1714-1728. doi:10.1016/j.chest.2021.05.041
- Kerlin MP et al. Ann Am Thorac Soc. 2022;19(2):329-331. doi:10.1513/AnnalsATS.202105-567RL
- Dean W et al. Fed Pract. 2019;36(9):400-402. PMID: 31571807
- Association of American Medical Colleges. The Complexities of Physician Supply and Demand: Projections from 2019 to 2034. June 2021. https://www.aamc.org/media/54681/download?attachment
- Medscape Pulmonologist Lifestyle, Happiness & Burnout Report 2023: Contentment Amid Stress. February 24, 2023. Accessed June 28, 2023. https://www.medscape.com/slideshow/2023-lifestyle-pulmonologist-6016092#1
- Medscape Intensivist Lifestyle, Happiness & Burnout Report 2023: Contentment Amid Stress. February 24, 2023. Accessed June 28, 2023. https://www.medscape.com/slideshow/2023-lifestyle-intensivist-6016072#1
- Moss M et al. Crit Care Med. 2016;44(7):1414-1421. doi:10.1097/CCM.000000000000188
- Medscape National Physician Burnout, Depression & Suicide Report 2019. Medscape. January 16, 2019. Accessed June 22, 2023. https://www.medscape.com/slideshow/2019-lifestyle-burnout-depression-6011056#1
- Medscape National Physician Burnout & Suicide Report 2020: The Generational Divide. Medscape. January 15, 2020. Accessed June 22, 2023. https://www.medscape.com/slideshow/2020-lifestyle-burnout-6012460#1
- ‘Death by 1000 Cuts’: Medscape National Physician Burnout & Suicide Report 2021. Medscape. January 22, 2021. Accessed June 22, 2023. https://www.medscape.com/slideshow/2021-lifestyle-burnout-6013456#2
- Physician Burnout Report 2022: Stress, Anxiety, and Anger. Medscape. January 21, 2022. Accessed June 22, 2023. https://www.medscape.com/slideshow/2022-lifestyle-burnout-6014664#1
- ‘I Cry but No One Cares’: Physician Burnout & Depression Report 2023. Medscape. January 27, 2023. Accessed June 22, 2023. https://www.medscape.com/slideshow/2023-lifestyle-burnout-6016058#1
- Murthy VH. N Engl J Med. 2022;387(7):577-579. doi:10.1056/NEJMp2207252
- Vranas KC et al. Chest. 2021;160(5):1714-1728. doi:10.1016/j.chest.2021.05.041
- Kerlin MP et al. Ann Am Thorac Soc. 2022;19(2):329-331. doi:10.1513/AnnalsATS.202105-567RL
- Dean W et al. Fed Pract. 2019;36(9):400-402. PMID: 31571807
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