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INPULSIS-ON: Nintedanib shows manageable long-term safety for IPF
For patients with showed acceptable safety and tolerability and might have slowed disease progression, according to the results of the open-label INPULSIS-ON trial.
No new safety signals were identified among patients who continued nintedanib or switched from placebo to the medication after completing one of the two 52-week phase 3 INPULSIS trials, reported Bruno Crestani, MD, of H
Idiopathic pulmonary fibrosis has had a poor prognosis – before antifibrotic therapy became available in the United States, median survival after diagnosis was estimated at 3-5 years, the researchers noted. Patients often die or deteriorate because of acute declines in respiratory function, often from unknown causes. Nintedanib (Ofev) is an intracellular tyrosine kinase inhibitor first approved for idiopathic pulmonary fibrosis in the United States in 2014, based on the results of the replicate randomized, placebo-controlled, double-blind, phase 3 INPULSIS trials, in which nintedanib (150 mg twice daily) was usually tolerable, showed an acceptable overall toxicity profile, and significantly lessened the annual rate of decline in forced vital capacity (FVC), compared with placebo.
Because idiopathic pulmonary fibrosis has a chronic trajectory, data on long-term safety and efficacy were clearly desirable. “Results from the open-label extension of the [foundational] phase 2 TOMORROW trial [also] identified no new safety signals and suggested an effect of nintedanib on slowing the progression of idiopathic pulmonary fibrosis beyond 52 weeks; however, only 35 patients treated with nintedanib 150 mg twice daily entered the extension study,” Dr. Crestani and his associates noted.
The open-label INPULSIS-ON extension trial included 734 patients, which was 91% of the population that completed the INPULSIS trials. A total of 59% patients in the open-label trial continued nintedanib while the rest switched to nintedanib from placebo. When considering both cohorts, the median duration of exposure to nintedanib was 44.7 months (range, 1.9-68.3 months).
Rates of major adverse cardiovascular events were 2.4 per 100 person-years of drug exposure among treatment initiators and 3.6 per 100 person-years among continuers, the researchers reported. Rates of bleeding were 6.7 and 8.4 events per 100 person-years, respectively, while rates of myocardial infarction, using the broadest possible definition, were 0.7 and 1.3 events per 100 person-years, respectively. The most common adverse event was diarrhea, with 60.1 and 71.2 events per 100 person-years among treatment initiators and continuers, respectively. In all, 10% of treatment initiators and 5% of continuers stopped nintedanib because of diarrhea. A total of 14% of treatment initiators and 12% of continuers stopped treatment because they experienced progression of idiopathic pulmonary fibrosis, making this adverse event the most common reason to stop treatment.
The adjusted annual rate of decline in FVC was −135.1 mL overall, –145 mL in nintedanib continuers, and –119.7 mL in nintedanib initiators, which resembled the findings of the INPULSIS trials, the researcher said. They added that the difference in FVC decline between INPULSIS-ON nintedanib initiators and continuers does not seem clinically meaningful, especially given that the average FVC decline in the INPULSIS placebo group was −223.5 mL per year, and the minimal clinically important difference in FVC is thought to be 2%-6% predicted, a difference of at least 75 mL-80 mL.
Boehringer Ingelheim funded the study. Dr. Crestani disclosed grants and personal fees from Boehringer Ingelheim and Roche, grants from Apellis and MedImmune, and personal fees from AstraZeneca and Sanofi.
SOURCE: Crestani B et al. Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600(18)30339-4.
The study provides “invaluable safety data, including a very low incidence of cardiovascular events” among patients who received long-term nintedanib therapy for idiopathic pulmonary fibrosis, wrote Athol U. Wells, MD, in an editorial published alongside the study.
But the efficacy data were substantially more problematic, he said. “At first sight, the data seem to show that treatment benefits are sustained during long-term follow-up. However, this finding applied to patients completing 4 years of treatment. Approximately 70% of patients discontinued nintedanib [during the open-label extension trial].”
Death, probable treatment failure, or adverse events unrelated to idiopathic pulmonary fibrosis accounted for 62% of withdrawals from this study, and the investigators did not present FVC trends for these patients, he noted. This makes it difficult to know whether bias affected the efficacy results. Long-term stability or slow progression was seen in 30%-40% of patients, exceeding results from previous IPF cohorts, but “this finding, although encouraging, is clearly non-definitive.”
The mortality data also were problematic because the trial excluded patients with major comorbidities and severe disease, and the researchers only tracked vital status for 6 weeks after patients withdrew from INPULSIS-ON, he said. “One cannot help but feel that a major opportunity was lost in this study and, equally, in the pirfenidone extension study. An intention-to-treat study design would have provided invaluable long-term efficacy data and should be prioritized in future.”
Dr. Wells is with Royal Brompton Hospital in London. He disclosed personal fees from Boehringer Ingelheim, Intermune/Roche, Bayer, Actelion, and Raffo, outside the submitted work (Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600[18]30385-0).
The study provides “invaluable safety data, including a very low incidence of cardiovascular events” among patients who received long-term nintedanib therapy for idiopathic pulmonary fibrosis, wrote Athol U. Wells, MD, in an editorial published alongside the study.
But the efficacy data were substantially more problematic, he said. “At first sight, the data seem to show that treatment benefits are sustained during long-term follow-up. However, this finding applied to patients completing 4 years of treatment. Approximately 70% of patients discontinued nintedanib [during the open-label extension trial].”
Death, probable treatment failure, or adverse events unrelated to idiopathic pulmonary fibrosis accounted for 62% of withdrawals from this study, and the investigators did not present FVC trends for these patients, he noted. This makes it difficult to know whether bias affected the efficacy results. Long-term stability or slow progression was seen in 30%-40% of patients, exceeding results from previous IPF cohorts, but “this finding, although encouraging, is clearly non-definitive.”
The mortality data also were problematic because the trial excluded patients with major comorbidities and severe disease, and the researchers only tracked vital status for 6 weeks after patients withdrew from INPULSIS-ON, he said. “One cannot help but feel that a major opportunity was lost in this study and, equally, in the pirfenidone extension study. An intention-to-treat study design would have provided invaluable long-term efficacy data and should be prioritized in future.”
Dr. Wells is with Royal Brompton Hospital in London. He disclosed personal fees from Boehringer Ingelheim, Intermune/Roche, Bayer, Actelion, and Raffo, outside the submitted work (Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600[18]30385-0).
The study provides “invaluable safety data, including a very low incidence of cardiovascular events” among patients who received long-term nintedanib therapy for idiopathic pulmonary fibrosis, wrote Athol U. Wells, MD, in an editorial published alongside the study.
But the efficacy data were substantially more problematic, he said. “At first sight, the data seem to show that treatment benefits are sustained during long-term follow-up. However, this finding applied to patients completing 4 years of treatment. Approximately 70% of patients discontinued nintedanib [during the open-label extension trial].”
Death, probable treatment failure, or adverse events unrelated to idiopathic pulmonary fibrosis accounted for 62% of withdrawals from this study, and the investigators did not present FVC trends for these patients, he noted. This makes it difficult to know whether bias affected the efficacy results. Long-term stability or slow progression was seen in 30%-40% of patients, exceeding results from previous IPF cohorts, but “this finding, although encouraging, is clearly non-definitive.”
The mortality data also were problematic because the trial excluded patients with major comorbidities and severe disease, and the researchers only tracked vital status for 6 weeks after patients withdrew from INPULSIS-ON, he said. “One cannot help but feel that a major opportunity was lost in this study and, equally, in the pirfenidone extension study. An intention-to-treat study design would have provided invaluable long-term efficacy data and should be prioritized in future.”
Dr. Wells is with Royal Brompton Hospital in London. He disclosed personal fees from Boehringer Ingelheim, Intermune/Roche, Bayer, Actelion, and Raffo, outside the submitted work (Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600[18]30385-0).
For patients with showed acceptable safety and tolerability and might have slowed disease progression, according to the results of the open-label INPULSIS-ON trial.
No new safety signals were identified among patients who continued nintedanib or switched from placebo to the medication after completing one of the two 52-week phase 3 INPULSIS trials, reported Bruno Crestani, MD, of H
Idiopathic pulmonary fibrosis has had a poor prognosis – before antifibrotic therapy became available in the United States, median survival after diagnosis was estimated at 3-5 years, the researchers noted. Patients often die or deteriorate because of acute declines in respiratory function, often from unknown causes. Nintedanib (Ofev) is an intracellular tyrosine kinase inhibitor first approved for idiopathic pulmonary fibrosis in the United States in 2014, based on the results of the replicate randomized, placebo-controlled, double-blind, phase 3 INPULSIS trials, in which nintedanib (150 mg twice daily) was usually tolerable, showed an acceptable overall toxicity profile, and significantly lessened the annual rate of decline in forced vital capacity (FVC), compared with placebo.
Because idiopathic pulmonary fibrosis has a chronic trajectory, data on long-term safety and efficacy were clearly desirable. “Results from the open-label extension of the [foundational] phase 2 TOMORROW trial [also] identified no new safety signals and suggested an effect of nintedanib on slowing the progression of idiopathic pulmonary fibrosis beyond 52 weeks; however, only 35 patients treated with nintedanib 150 mg twice daily entered the extension study,” Dr. Crestani and his associates noted.
The open-label INPULSIS-ON extension trial included 734 patients, which was 91% of the population that completed the INPULSIS trials. A total of 59% patients in the open-label trial continued nintedanib while the rest switched to nintedanib from placebo. When considering both cohorts, the median duration of exposure to nintedanib was 44.7 months (range, 1.9-68.3 months).
Rates of major adverse cardiovascular events were 2.4 per 100 person-years of drug exposure among treatment initiators and 3.6 per 100 person-years among continuers, the researchers reported. Rates of bleeding were 6.7 and 8.4 events per 100 person-years, respectively, while rates of myocardial infarction, using the broadest possible definition, were 0.7 and 1.3 events per 100 person-years, respectively. The most common adverse event was diarrhea, with 60.1 and 71.2 events per 100 person-years among treatment initiators and continuers, respectively. In all, 10% of treatment initiators and 5% of continuers stopped nintedanib because of diarrhea. A total of 14% of treatment initiators and 12% of continuers stopped treatment because they experienced progression of idiopathic pulmonary fibrosis, making this adverse event the most common reason to stop treatment.
The adjusted annual rate of decline in FVC was −135.1 mL overall, –145 mL in nintedanib continuers, and –119.7 mL in nintedanib initiators, which resembled the findings of the INPULSIS trials, the researcher said. They added that the difference in FVC decline between INPULSIS-ON nintedanib initiators and continuers does not seem clinically meaningful, especially given that the average FVC decline in the INPULSIS placebo group was −223.5 mL per year, and the minimal clinically important difference in FVC is thought to be 2%-6% predicted, a difference of at least 75 mL-80 mL.
Boehringer Ingelheim funded the study. Dr. Crestani disclosed grants and personal fees from Boehringer Ingelheim and Roche, grants from Apellis and MedImmune, and personal fees from AstraZeneca and Sanofi.
SOURCE: Crestani B et al. Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600(18)30339-4.
For patients with showed acceptable safety and tolerability and might have slowed disease progression, according to the results of the open-label INPULSIS-ON trial.
No new safety signals were identified among patients who continued nintedanib or switched from placebo to the medication after completing one of the two 52-week phase 3 INPULSIS trials, reported Bruno Crestani, MD, of H
Idiopathic pulmonary fibrosis has had a poor prognosis – before antifibrotic therapy became available in the United States, median survival after diagnosis was estimated at 3-5 years, the researchers noted. Patients often die or deteriorate because of acute declines in respiratory function, often from unknown causes. Nintedanib (Ofev) is an intracellular tyrosine kinase inhibitor first approved for idiopathic pulmonary fibrosis in the United States in 2014, based on the results of the replicate randomized, placebo-controlled, double-blind, phase 3 INPULSIS trials, in which nintedanib (150 mg twice daily) was usually tolerable, showed an acceptable overall toxicity profile, and significantly lessened the annual rate of decline in forced vital capacity (FVC), compared with placebo.
Because idiopathic pulmonary fibrosis has a chronic trajectory, data on long-term safety and efficacy were clearly desirable. “Results from the open-label extension of the [foundational] phase 2 TOMORROW trial [also] identified no new safety signals and suggested an effect of nintedanib on slowing the progression of idiopathic pulmonary fibrosis beyond 52 weeks; however, only 35 patients treated with nintedanib 150 mg twice daily entered the extension study,” Dr. Crestani and his associates noted.
The open-label INPULSIS-ON extension trial included 734 patients, which was 91% of the population that completed the INPULSIS trials. A total of 59% patients in the open-label trial continued nintedanib while the rest switched to nintedanib from placebo. When considering both cohorts, the median duration of exposure to nintedanib was 44.7 months (range, 1.9-68.3 months).
Rates of major adverse cardiovascular events were 2.4 per 100 person-years of drug exposure among treatment initiators and 3.6 per 100 person-years among continuers, the researchers reported. Rates of bleeding were 6.7 and 8.4 events per 100 person-years, respectively, while rates of myocardial infarction, using the broadest possible definition, were 0.7 and 1.3 events per 100 person-years, respectively. The most common adverse event was diarrhea, with 60.1 and 71.2 events per 100 person-years among treatment initiators and continuers, respectively. In all, 10% of treatment initiators and 5% of continuers stopped nintedanib because of diarrhea. A total of 14% of treatment initiators and 12% of continuers stopped treatment because they experienced progression of idiopathic pulmonary fibrosis, making this adverse event the most common reason to stop treatment.
The adjusted annual rate of decline in FVC was −135.1 mL overall, –145 mL in nintedanib continuers, and –119.7 mL in nintedanib initiators, which resembled the findings of the INPULSIS trials, the researcher said. They added that the difference in FVC decline between INPULSIS-ON nintedanib initiators and continuers does not seem clinically meaningful, especially given that the average FVC decline in the INPULSIS placebo group was −223.5 mL per year, and the minimal clinically important difference in FVC is thought to be 2%-6% predicted, a difference of at least 75 mL-80 mL.
Boehringer Ingelheim funded the study. Dr. Crestani disclosed grants and personal fees from Boehringer Ingelheim and Roche, grants from Apellis and MedImmune, and personal fees from AstraZeneca and Sanofi.
SOURCE: Crestani B et al. Lancet Respir Med. 2018 Sep 14. doi: 10.1016/S2213-2600(18)30339-4.
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: Nintedanib showed manageable safety and tolerability and might have helped conserve forced vital capacity during long-term use for the treatment of IPF.
Major finding: No new safety signals were found over up to 68 months of treatment.
Study details: Open-label extension study of nintedanib initiation or continuation in 734 patients with idiopathic pulmonary fibrosis (median drug exposure 44.7 months; range, 11.9-68.3 months).
Disclosures: Boehringer Ingelheim funded the study. Dr. Crestani disclosed grants and personal fees from Boehringer Ingelheim and Roche, grants from Apellis and MedImmune, and personal fees from AstraZeneca and Sanofi.
Source: Crestani B et al. Lancet Respir Med. 2018 Sep 14.
Lung screening complications costly, more prevalent than in trial setting
The real-world rate of is substantially higher than in clinical trials, a study suggests.
Those complications related to low-dose computed tomography (LDCT) screening are potentially costly, according to the analysis of commercial and Medicare claims data for nearly 350,000 individuals.
While tentative, these results emphasize the need to discuss the risk of adverse events and their costs as part of the shared decision-making process between physicians and patients, researchers said in a report on their study in JAMA Internal Medicine.
“As the number of individuals seeking lung cancer screening with LDCT increases, so too will the number of individuals undergoing invasive diagnostic procedures as a results of abnormal findings,” said Jinhai Huo, MD, PhD, of the department of health services research, management, and policy at the University of Florida, Gainesville.
The retrospective cohort study included 174,702 individuals who underwent an invasive diagnostic procedure related to lung cancer screening and 169,808 control subjects.
All individuals studied were between 55 and 77 years old, the targeted age range for lung cancer screening specified by the Centers for Medicare & Medicaid Services.
Complication rates were about twice as high as they were in the landmark National Lung Screening Trial (NLST), both for a younger cohort of individuals aged 55-64 years, and an older Medicare age group of individuals aged 65 to 77 years, Dr. Huo and coinvestigators reported.
The estimated rate of complications was 22.0% (95% confidence interval, 21.7%-22.7%) in the younger age group, and even higher in the older age group, at 23.8% (95% CI, 23.0%-24.6%), according to investigators. By contrast, complication rates in the NLST were 9.8% and 8.5% for younger and older age cohorts, respectively.
The cost of managing postprocedural complications was higher than the cost of the diagnostic procedures, investigators said.
Mean costs ranged from $6,320 for minor complications to $56,845 for major complications, they reported.
The most common invasive diagnostic procedure in the study cohort was cytology test or biopsy in 26.1%, followed by bronchoscopy in 25.6%, according to study data. Another 5.4% underwent thoracic surgery.
In a previous Medicare advisory committee meeting, some experts expressed concern that complication rates in settings outside of the NLST would be higher than what was reported in that study, Dr. Huo and coauthors noted in their report.
“Our findings echoed this concern,” they said in a discussion of their results.
Dr. Huo and coauthors reported no conflicts of interest related to the research, which was supported in part by grants or fellowships from the University of Texas MD Anderson Cancer Center, the University of Florida, the National Cancer Institute, and the National Institutes of Health.
SOURCE: Huo J et al. JAMA Intern Med. 2019 Jan 14.
“The conversations that are occurring about lung cancer screening are woefully inadequate and do not discuss harms,” wrote Rita F. Redberg, MD, in an editorial note. Shared decision-making visits were made mandatory prior to lung cancer screening by the Centers for Medicare & Medicaid Services. That decision was made because of an evidence review suggesting a “low likelihood” that benefits of lung cancer screening would exceed harms in the Medicare population, Dr. Redberg wrote. Despite that, most Medicare beneficiaries are not having the required visit for shared decision making before they undergo the CT scan.
“It is likely that patients’ decisions not to undergo low-dose computed tomography for lung cancer screening are driven by the high false-positive rate, high chance of incidental findings, and subsequent need for invasive procedures, and small chance of benefit,” she said in her comment.
Shared decision-making visits are also rarely happening in the privately insured population, as shown in previous research, Dr. Redberg noted.
She reported no conflicts of interest related to her Editor’s Note, which appears in JAMA Internal Medicine (2019 Jan 14).
Dr. Redberg is with the department of medicine, University of California, San Francisco.
“The conversations that are occurring about lung cancer screening are woefully inadequate and do not discuss harms,” wrote Rita F. Redberg, MD, in an editorial note. Shared decision-making visits were made mandatory prior to lung cancer screening by the Centers for Medicare & Medicaid Services. That decision was made because of an evidence review suggesting a “low likelihood” that benefits of lung cancer screening would exceed harms in the Medicare population, Dr. Redberg wrote. Despite that, most Medicare beneficiaries are not having the required visit for shared decision making before they undergo the CT scan.
“It is likely that patients’ decisions not to undergo low-dose computed tomography for lung cancer screening are driven by the high false-positive rate, high chance of incidental findings, and subsequent need for invasive procedures, and small chance of benefit,” she said in her comment.
Shared decision-making visits are also rarely happening in the privately insured population, as shown in previous research, Dr. Redberg noted.
She reported no conflicts of interest related to her Editor’s Note, which appears in JAMA Internal Medicine (2019 Jan 14).
Dr. Redberg is with the department of medicine, University of California, San Francisco.
“The conversations that are occurring about lung cancer screening are woefully inadequate and do not discuss harms,” wrote Rita F. Redberg, MD, in an editorial note. Shared decision-making visits were made mandatory prior to lung cancer screening by the Centers for Medicare & Medicaid Services. That decision was made because of an evidence review suggesting a “low likelihood” that benefits of lung cancer screening would exceed harms in the Medicare population, Dr. Redberg wrote. Despite that, most Medicare beneficiaries are not having the required visit for shared decision making before they undergo the CT scan.
“It is likely that patients’ decisions not to undergo low-dose computed tomography for lung cancer screening are driven by the high false-positive rate, high chance of incidental findings, and subsequent need for invasive procedures, and small chance of benefit,” she said in her comment.
Shared decision-making visits are also rarely happening in the privately insured population, as shown in previous research, Dr. Redberg noted.
She reported no conflicts of interest related to her Editor’s Note, which appears in JAMA Internal Medicine (2019 Jan 14).
Dr. Redberg is with the department of medicine, University of California, San Francisco.
The real-world rate of is substantially higher than in clinical trials, a study suggests.
Those complications related to low-dose computed tomography (LDCT) screening are potentially costly, according to the analysis of commercial and Medicare claims data for nearly 350,000 individuals.
While tentative, these results emphasize the need to discuss the risk of adverse events and their costs as part of the shared decision-making process between physicians and patients, researchers said in a report on their study in JAMA Internal Medicine.
“As the number of individuals seeking lung cancer screening with LDCT increases, so too will the number of individuals undergoing invasive diagnostic procedures as a results of abnormal findings,” said Jinhai Huo, MD, PhD, of the department of health services research, management, and policy at the University of Florida, Gainesville.
The retrospective cohort study included 174,702 individuals who underwent an invasive diagnostic procedure related to lung cancer screening and 169,808 control subjects.
All individuals studied were between 55 and 77 years old, the targeted age range for lung cancer screening specified by the Centers for Medicare & Medicaid Services.
Complication rates were about twice as high as they were in the landmark National Lung Screening Trial (NLST), both for a younger cohort of individuals aged 55-64 years, and an older Medicare age group of individuals aged 65 to 77 years, Dr. Huo and coinvestigators reported.
The estimated rate of complications was 22.0% (95% confidence interval, 21.7%-22.7%) in the younger age group, and even higher in the older age group, at 23.8% (95% CI, 23.0%-24.6%), according to investigators. By contrast, complication rates in the NLST were 9.8% and 8.5% for younger and older age cohorts, respectively.
The cost of managing postprocedural complications was higher than the cost of the diagnostic procedures, investigators said.
Mean costs ranged from $6,320 for minor complications to $56,845 for major complications, they reported.
The most common invasive diagnostic procedure in the study cohort was cytology test or biopsy in 26.1%, followed by bronchoscopy in 25.6%, according to study data. Another 5.4% underwent thoracic surgery.
In a previous Medicare advisory committee meeting, some experts expressed concern that complication rates in settings outside of the NLST would be higher than what was reported in that study, Dr. Huo and coauthors noted in their report.
“Our findings echoed this concern,” they said in a discussion of their results.
Dr. Huo and coauthors reported no conflicts of interest related to the research, which was supported in part by grants or fellowships from the University of Texas MD Anderson Cancer Center, the University of Florida, the National Cancer Institute, and the National Institutes of Health.
SOURCE: Huo J et al. JAMA Intern Med. 2019 Jan 14.
The real-world rate of is substantially higher than in clinical trials, a study suggests.
Those complications related to low-dose computed tomography (LDCT) screening are potentially costly, according to the analysis of commercial and Medicare claims data for nearly 350,000 individuals.
While tentative, these results emphasize the need to discuss the risk of adverse events and their costs as part of the shared decision-making process between physicians and patients, researchers said in a report on their study in JAMA Internal Medicine.
“As the number of individuals seeking lung cancer screening with LDCT increases, so too will the number of individuals undergoing invasive diagnostic procedures as a results of abnormal findings,” said Jinhai Huo, MD, PhD, of the department of health services research, management, and policy at the University of Florida, Gainesville.
The retrospective cohort study included 174,702 individuals who underwent an invasive diagnostic procedure related to lung cancer screening and 169,808 control subjects.
All individuals studied were between 55 and 77 years old, the targeted age range for lung cancer screening specified by the Centers for Medicare & Medicaid Services.
Complication rates were about twice as high as they were in the landmark National Lung Screening Trial (NLST), both for a younger cohort of individuals aged 55-64 years, and an older Medicare age group of individuals aged 65 to 77 years, Dr. Huo and coinvestigators reported.
The estimated rate of complications was 22.0% (95% confidence interval, 21.7%-22.7%) in the younger age group, and even higher in the older age group, at 23.8% (95% CI, 23.0%-24.6%), according to investigators. By contrast, complication rates in the NLST were 9.8% and 8.5% for younger and older age cohorts, respectively.
The cost of managing postprocedural complications was higher than the cost of the diagnostic procedures, investigators said.
Mean costs ranged from $6,320 for minor complications to $56,845 for major complications, they reported.
The most common invasive diagnostic procedure in the study cohort was cytology test or biopsy in 26.1%, followed by bronchoscopy in 25.6%, according to study data. Another 5.4% underwent thoracic surgery.
In a previous Medicare advisory committee meeting, some experts expressed concern that complication rates in settings outside of the NLST would be higher than what was reported in that study, Dr. Huo and coauthors noted in their report.
“Our findings echoed this concern,” they said in a discussion of their results.
Dr. Huo and coauthors reported no conflicts of interest related to the research, which was supported in part by grants or fellowships from the University of Texas MD Anderson Cancer Center, the University of Florida, the National Cancer Institute, and the National Institutes of Health.
SOURCE: Huo J et al. JAMA Intern Med. 2019 Jan 14.
FROM JAMA INTERNAL MEDICINE
Key clinical point: The risk of complications following lung cancer screening is higher in a real-world setting as compared with the landmark National Lung Screening Trial (NLST).
Major finding: Estimated complication rates were 22.0%-23.8%, compared with 8.5%-9.8% in the NLST.
Study details: A retrospective cohort study including 174,702 individuals who underwent an invasive diagnostic procedure related to lung cancer screening and 169,808 controls.
Disclosures: Authors reported no conflicts of interest. The research was supported in part by grants or fellowships from the University of Texas MD Anderson Cancer Center, the University of Florida, the National Cancer Institute, and the National Institutes of Health.
Source: Huo J et al. JAMA Intern Med. 2019 Jan 14.
New Section Editor for Pulmonary Perspectives®
We are pleased to announce Corey Kershaw, MD, as the new Section Editor for Pulmonary Perspectives. Dr. Kershaw is the Medical Director of the Medical Intensive Care Unit at Clements University Hospital and an Associate Professor, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, in Dallas, Texas. He currently serves on the American College of Chest Physicians Interstitial and Diffuse Lung Disease NetWork. Dr. Kershaw’s research interests revolve around clinical trials for the treatment of idiopathic pulmonary fibrosis and other fibrosing interstitial lung diseases.
We thank Nitin Puri, MD, FCCP, for his outstanding service as the Pulmonary Perspectives Section Editor for the previous 3
We are pleased to announce Corey Kershaw, MD, as the new Section Editor for Pulmonary Perspectives. Dr. Kershaw is the Medical Director of the Medical Intensive Care Unit at Clements University Hospital and an Associate Professor, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, in Dallas, Texas. He currently serves on the American College of Chest Physicians Interstitial and Diffuse Lung Disease NetWork. Dr. Kershaw’s research interests revolve around clinical trials for the treatment of idiopathic pulmonary fibrosis and other fibrosing interstitial lung diseases.
We thank Nitin Puri, MD, FCCP, for his outstanding service as the Pulmonary Perspectives Section Editor for the previous 3
We are pleased to announce Corey Kershaw, MD, as the new Section Editor for Pulmonary Perspectives. Dr. Kershaw is the Medical Director of the Medical Intensive Care Unit at Clements University Hospital and an Associate Professor, Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, in Dallas, Texas. He currently serves on the American College of Chest Physicians Interstitial and Diffuse Lung Disease NetWork. Dr. Kershaw’s research interests revolve around clinical trials for the treatment of idiopathic pulmonary fibrosis and other fibrosing interstitial lung diseases.
We thank Nitin Puri, MD, FCCP, for his outstanding service as the Pulmonary Perspectives Section Editor for the previous 3
More benefit to chemoradiation in earlier small cell lung cancer
In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.
The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.
The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.
Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.
Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.
At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.
However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).
Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.
The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.
“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.
The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.
“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.
SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.
In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.
The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.
The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.
Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.
Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.
At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.
However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).
Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.
The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.
“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.
The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.
“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.
SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.
In response to chemoradiation, patients with stage I or II small cell lung cancer (SCLC) have a significantly longer overall survival than do those with stage III disease, according to a post hoc analysis of a randomized trial of chemoradiation in patients with early stages of SCLC.
The fact that overall survival is better in stage I and II than in stage III SCLC isn’t surprising. But the data confirm that stage I and II SCLC responds differently to chemoradiation than does stage III, providing a benchmark for safety and efficacy, according to the study authors.
The phase 3 CONVERT trial, from which the data were drawn, randomized patients with limited-stage SCLC to twice-daily (45 Gy in 30 fractions) or once-daily (66 Gy in 33 fractions) radiation after initiating cisplatin-etoposide chemotherapy (Lancet Oncol. 2017 Aug;18[8]:1116-25). Additional prophylactic cranial irradiation was permitted for those with an indication.
Contrary to the researcher’s hypothesis, once-daily radiation was not more effective for the primary outcome of overall survival in CONVERT, which limited enrollment to patients with local disease but did not stratify outcomes by SCLC stage. The purpose of the new post hoc analysis was to compare outcomes in those early-disease SCLC patients stratified by stage, which the authors noted is now recommended by several guidelines.
Because there were only four patients in CONVERT with stage I SCLC, those with either stage I or II SCLC, totaling 86 patients, were combined and then compared with the 423 with stage III SCLC.
At baseline, there were no significant differences between stage I/II and III groups for median age, smoking history, ECOG performance status, or dyspnea score at baseline. Similar proportions of patients completed the planned therapy.
However, the median survival was twice as long in the stage I/II group, compared with those with stage III SCLC (50 vs. 25 months), producing a hazard ratio for this outcome of 0.60 (P = .001). At 5 years, 49% of the stage I/II patients were alive, compared with 28% of the stage III patients (P = .001).
Other outcomes, such as progression-free survival at 5 years (47% vs. 26%; P = .003) also favored those with earlier-stage disease.
The incidence of adverse events associated with chemoradiation was not significantly different for the two groups, with the exception of acute esophagitis, which was less frequent in patients with earlier stage disease.
“The low incidence of severe toxic effects is a valid rationale to consider future radiotherapy dose intensification trials to improve outcomes” in patients with stage I/II disease, according to study author Ahmed Salem, MB, ChB, of the University of Manchester, England, and his coinvestigators.
The data from the post hoc analysis support guideline recommendations to stage even early and local SCLC when evaluating response to therapy in clinical trials, noted Howard (Jack) West, MD, of Swedish Cancer Institute, Seattle, in an accompanying editorial (JAMA Oncol. 2018 Dec 6. doi: 10.1001/jamaoncol.2018.5187). Dr. West suggested that such staging information might be useful when counseling patients about treatment options.
“These results imply that we may do our patients a disservice by dispensing with clinically relevant staging information that can lead to a more refined assessment of prognosis and optimal treatment,” Dr. West wrote.
SOURCE: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.
FROM JAMA ONCOLOGY
Key clinical point: Overall survival after chemoradiation is longer in stages I and II versus stage III small cell lung cancer.
Major finding: The hazard ratio for overall survival was 0.60 (P = .001), signifying 40% risk reduction for stage I/II versus stage III SCLC.
Study details: A post hoc secondary analysis of a phase 3 randomized trial.
Disclosures: The authors declared no potential conflicts of interest.
Source: Salem A et al. JAMA Oncol. 2018 Dec 6:e185335. doi: 10.1001/jamaoncol.2018.5335.
Flu season showing signs of decline
The 2018-2019 flu season may have peaked as measures of influenza-like illness (ILI) activity dropped in the first week of the new year, according to the U.S. Centers for Disease Control and Prevention.
The proportion of outpatients visits for ILI dropped to 3.5% for the week ending Jan. 5, 2019, after reaching 4.0% the previous week. Outpatient ILI visits first topped the national baseline of 2.2% during the week ending Dec. 8, 2018, and have remained above that value for 5 consecutive weeks, the CDC’s influenza division said on Jan. 11.
Flu activity reported by the states reflects the national drop: 10 states came in at level 10 on the CDC’s 1-10 scale of activity for the week ending Jan. 5 – down from 12 the week before – and a total of 15 were in the high range from 8 to 10, compared with 19 the previous week, the CDC said. Two states, Mississippi and Texas, dropped from level 10 to level 7, which the CDC categorizes as moderate activity.
A total of 73 ILI-related deaths were reported during the week ending Dec. 29 (the latest with data available; reporting less than 68% complete), which already exceeds the 71 deaths reported for the week ending Dec. 22 (reporting 85% complete). Flu deaths totaled 437 through the first 13 weeks of the 2018-2019 season, compared with the 1,659 that occurred during weeks 1-13 of the very severe 2017-2018 season, CDC data show.
For the week ending Jan. 5, the CDC received reports of three flu-related pediatric deaths, all of which occurred the previous week. For the season so far, there have been 16 pediatric deaths, compared with 20 at this point in the 2017-2018 season.
Estimates released during the flu season for the first time show that between 6 and 7 million Americans have been infected since Oct. 1, 2018, and that 69,000-84,000 people have been hospitalized with the flu through Jan. 5, 2019. These cumulative totals have previously been available only at the end of the season, the CDC noted.
The 2018-2019 flu season may have peaked as measures of influenza-like illness (ILI) activity dropped in the first week of the new year, according to the U.S. Centers for Disease Control and Prevention.
The proportion of outpatients visits for ILI dropped to 3.5% for the week ending Jan. 5, 2019, after reaching 4.0% the previous week. Outpatient ILI visits first topped the national baseline of 2.2% during the week ending Dec. 8, 2018, and have remained above that value for 5 consecutive weeks, the CDC’s influenza division said on Jan. 11.
Flu activity reported by the states reflects the national drop: 10 states came in at level 10 on the CDC’s 1-10 scale of activity for the week ending Jan. 5 – down from 12 the week before – and a total of 15 were in the high range from 8 to 10, compared with 19 the previous week, the CDC said. Two states, Mississippi and Texas, dropped from level 10 to level 7, which the CDC categorizes as moderate activity.
A total of 73 ILI-related deaths were reported during the week ending Dec. 29 (the latest with data available; reporting less than 68% complete), which already exceeds the 71 deaths reported for the week ending Dec. 22 (reporting 85% complete). Flu deaths totaled 437 through the first 13 weeks of the 2018-2019 season, compared with the 1,659 that occurred during weeks 1-13 of the very severe 2017-2018 season, CDC data show.
For the week ending Jan. 5, the CDC received reports of three flu-related pediatric deaths, all of which occurred the previous week. For the season so far, there have been 16 pediatric deaths, compared with 20 at this point in the 2017-2018 season.
Estimates released during the flu season for the first time show that between 6 and 7 million Americans have been infected since Oct. 1, 2018, and that 69,000-84,000 people have been hospitalized with the flu through Jan. 5, 2019. These cumulative totals have previously been available only at the end of the season, the CDC noted.
The 2018-2019 flu season may have peaked as measures of influenza-like illness (ILI) activity dropped in the first week of the new year, according to the U.S. Centers for Disease Control and Prevention.
The proportion of outpatients visits for ILI dropped to 3.5% for the week ending Jan. 5, 2019, after reaching 4.0% the previous week. Outpatient ILI visits first topped the national baseline of 2.2% during the week ending Dec. 8, 2018, and have remained above that value for 5 consecutive weeks, the CDC’s influenza division said on Jan. 11.
Flu activity reported by the states reflects the national drop: 10 states came in at level 10 on the CDC’s 1-10 scale of activity for the week ending Jan. 5 – down from 12 the week before – and a total of 15 were in the high range from 8 to 10, compared with 19 the previous week, the CDC said. Two states, Mississippi and Texas, dropped from level 10 to level 7, which the CDC categorizes as moderate activity.
A total of 73 ILI-related deaths were reported during the week ending Dec. 29 (the latest with data available; reporting less than 68% complete), which already exceeds the 71 deaths reported for the week ending Dec. 22 (reporting 85% complete). Flu deaths totaled 437 through the first 13 weeks of the 2018-2019 season, compared with the 1,659 that occurred during weeks 1-13 of the very severe 2017-2018 season, CDC data show.
For the week ending Jan. 5, the CDC received reports of three flu-related pediatric deaths, all of which occurred the previous week. For the season so far, there have been 16 pediatric deaths, compared with 20 at this point in the 2017-2018 season.
Estimates released during the flu season for the first time show that between 6 and 7 million Americans have been infected since Oct. 1, 2018, and that 69,000-84,000 people have been hospitalized with the flu through Jan. 5, 2019. These cumulative totals have previously been available only at the end of the season, the CDC noted.
Children who are coughing: Is it flu or bacterial pneumonia?
We are in the middle of flu season, and many of our patients are coughing. Is it the flu or might the child have a secondary bacterial pneumonia? Let’s start with the history for a tip off. The course of flu and respiratory viral infections in general involves a typical pattern of timing for fever and cough.
A late-developing fever or fever that subsides then recurs should raise concern. A prolonged cough or cough that subsides then recurs also should raise concern. The respiratory rate and chest retractions are key physical findings that can aid in distinguishing children with bacterial pneumonia. Rales and decreased breath sounds in lung segments are best heard with deep breaths.
What diagnostic laboratory and imaging tests should be used
Fortunately, rapid tests to detect influenza are available, and many providers have added those to their laboratory evaluation. A complete blood count and differential may be helpful. If a pulse oximeter is available, checking oxygen saturation might be helpful. The American Academy of Pediatrics community pneumonia guideline states that routine chest radiographs are not necessary for the confirmation of suspected community-acquired pneumonia (CAP) in patients well enough to be treated in the outpatient setting (Clin Inf Dis. 2011 Oct;53[7]:e25–e76). Blood cultures should not be performed routinely in nontoxic, fully immunized children with CAP managed in the outpatient setting.
What antibiotic should be used
Antimicrobial therapy is not routinely required for preschool-aged children with cough, even cough caused by CAP, because viral pathogens are responsible for the great majority of clinical disease. If the diagnosis of CAP is made, the AAP endorses amoxicillin as first-line therapy for previously healthy, appropriately immunized infants and preschool children with mild to moderate CAP suspected to be of bacterial origin. For previously healthy, appropriately immunized school-aged children and adolescents with mild to moderate CAP, amoxicillin is recommended for treatment of Streptococcus pneumoniae, the most prominent invasive bacterial pathogen.
However, the treatment paradigm is complicated because Mycoplasma pneumoniae also should be considered in management decisions. Children with signs and symptoms suspicious for M. pneumoniae should be tested to help guide antibiotic selection. This may be a simple bedside cold agglutinin test. The highest incidence of Mycoplasma pneumonia is in 5- to 20-year-olds (51% in 5- to 9-year-olds, 74% in 9- to 15-year-olds, and 3%-18% in adults with pneumonia), but 9% of CAP occurs in patients younger than 5 years old. The clinical features of Mycoplasma pneumonia resemble influenza: The patient has gradual onset of headache, malaise, fever, sore throat, and cough. Mycoplasma pneumonia has a similar incidence of productive cough, rales, and diarrhea as pneumococcal CAP, but with more frequent upper respiratory symptoms and a normal leukocyte count. Mycoplasma bronchopneumonia occurs 30 times more frequently than Mycoplasma lobar pneumonia. The radiologic features of Mycoplasma is typical of a bronchopneumonia, usually involving a single lobe, subsegmental atelectasis, peribronchial thickening, and streaky interstitial densities. While Mycoplasma pneumonia is usually self-limited, the duration of illness is shortened by oral treatment with doxycycline, erythromycin, clarithromycin, or azithromycin.
What is the appropriate duration of antimicrobial therapy
Recommendations by the AAP for CAP note that treatment courses of 10 days have been best studied, although shorter courses may be just as effective, particularly for mild disease managed on an outpatient basis.
When should children be hospitalized
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He had no conflicts to declare. Email him at pdnews@mdedge.com.
We are in the middle of flu season, and many of our patients are coughing. Is it the flu or might the child have a secondary bacterial pneumonia? Let’s start with the history for a tip off. The course of flu and respiratory viral infections in general involves a typical pattern of timing for fever and cough.
A late-developing fever or fever that subsides then recurs should raise concern. A prolonged cough or cough that subsides then recurs also should raise concern. The respiratory rate and chest retractions are key physical findings that can aid in distinguishing children with bacterial pneumonia. Rales and decreased breath sounds in lung segments are best heard with deep breaths.
What diagnostic laboratory and imaging tests should be used
Fortunately, rapid tests to detect influenza are available, and many providers have added those to their laboratory evaluation. A complete blood count and differential may be helpful. If a pulse oximeter is available, checking oxygen saturation might be helpful. The American Academy of Pediatrics community pneumonia guideline states that routine chest radiographs are not necessary for the confirmation of suspected community-acquired pneumonia (CAP) in patients well enough to be treated in the outpatient setting (Clin Inf Dis. 2011 Oct;53[7]:e25–e76). Blood cultures should not be performed routinely in nontoxic, fully immunized children with CAP managed in the outpatient setting.
What antibiotic should be used
Antimicrobial therapy is not routinely required for preschool-aged children with cough, even cough caused by CAP, because viral pathogens are responsible for the great majority of clinical disease. If the diagnosis of CAP is made, the AAP endorses amoxicillin as first-line therapy for previously healthy, appropriately immunized infants and preschool children with mild to moderate CAP suspected to be of bacterial origin. For previously healthy, appropriately immunized school-aged children and adolescents with mild to moderate CAP, amoxicillin is recommended for treatment of Streptococcus pneumoniae, the most prominent invasive bacterial pathogen.
However, the treatment paradigm is complicated because Mycoplasma pneumoniae also should be considered in management decisions. Children with signs and symptoms suspicious for M. pneumoniae should be tested to help guide antibiotic selection. This may be a simple bedside cold agglutinin test. The highest incidence of Mycoplasma pneumonia is in 5- to 20-year-olds (51% in 5- to 9-year-olds, 74% in 9- to 15-year-olds, and 3%-18% in adults with pneumonia), but 9% of CAP occurs in patients younger than 5 years old. The clinical features of Mycoplasma pneumonia resemble influenza: The patient has gradual onset of headache, malaise, fever, sore throat, and cough. Mycoplasma pneumonia has a similar incidence of productive cough, rales, and diarrhea as pneumococcal CAP, but with more frequent upper respiratory symptoms and a normal leukocyte count. Mycoplasma bronchopneumonia occurs 30 times more frequently than Mycoplasma lobar pneumonia. The radiologic features of Mycoplasma is typical of a bronchopneumonia, usually involving a single lobe, subsegmental atelectasis, peribronchial thickening, and streaky interstitial densities. While Mycoplasma pneumonia is usually self-limited, the duration of illness is shortened by oral treatment with doxycycline, erythromycin, clarithromycin, or azithromycin.
What is the appropriate duration of antimicrobial therapy
Recommendations by the AAP for CAP note that treatment courses of 10 days have been best studied, although shorter courses may be just as effective, particularly for mild disease managed on an outpatient basis.
When should children be hospitalized
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He had no conflicts to declare. Email him at pdnews@mdedge.com.
We are in the middle of flu season, and many of our patients are coughing. Is it the flu or might the child have a secondary bacterial pneumonia? Let’s start with the history for a tip off. The course of flu and respiratory viral infections in general involves a typical pattern of timing for fever and cough.
A late-developing fever or fever that subsides then recurs should raise concern. A prolonged cough or cough that subsides then recurs also should raise concern. The respiratory rate and chest retractions are key physical findings that can aid in distinguishing children with bacterial pneumonia. Rales and decreased breath sounds in lung segments are best heard with deep breaths.
What diagnostic laboratory and imaging tests should be used
Fortunately, rapid tests to detect influenza are available, and many providers have added those to their laboratory evaluation. A complete blood count and differential may be helpful. If a pulse oximeter is available, checking oxygen saturation might be helpful. The American Academy of Pediatrics community pneumonia guideline states that routine chest radiographs are not necessary for the confirmation of suspected community-acquired pneumonia (CAP) in patients well enough to be treated in the outpatient setting (Clin Inf Dis. 2011 Oct;53[7]:e25–e76). Blood cultures should not be performed routinely in nontoxic, fully immunized children with CAP managed in the outpatient setting.
What antibiotic should be used
Antimicrobial therapy is not routinely required for preschool-aged children with cough, even cough caused by CAP, because viral pathogens are responsible for the great majority of clinical disease. If the diagnosis of CAP is made, the AAP endorses amoxicillin as first-line therapy for previously healthy, appropriately immunized infants and preschool children with mild to moderate CAP suspected to be of bacterial origin. For previously healthy, appropriately immunized school-aged children and adolescents with mild to moderate CAP, amoxicillin is recommended for treatment of Streptococcus pneumoniae, the most prominent invasive bacterial pathogen.
However, the treatment paradigm is complicated because Mycoplasma pneumoniae also should be considered in management decisions. Children with signs and symptoms suspicious for M. pneumoniae should be tested to help guide antibiotic selection. This may be a simple bedside cold agglutinin test. The highest incidence of Mycoplasma pneumonia is in 5- to 20-year-olds (51% in 5- to 9-year-olds, 74% in 9- to 15-year-olds, and 3%-18% in adults with pneumonia), but 9% of CAP occurs in patients younger than 5 years old. The clinical features of Mycoplasma pneumonia resemble influenza: The patient has gradual onset of headache, malaise, fever, sore throat, and cough. Mycoplasma pneumonia has a similar incidence of productive cough, rales, and diarrhea as pneumococcal CAP, but with more frequent upper respiratory symptoms and a normal leukocyte count. Mycoplasma bronchopneumonia occurs 30 times more frequently than Mycoplasma lobar pneumonia. The radiologic features of Mycoplasma is typical of a bronchopneumonia, usually involving a single lobe, subsegmental atelectasis, peribronchial thickening, and streaky interstitial densities. While Mycoplasma pneumonia is usually self-limited, the duration of illness is shortened by oral treatment with doxycycline, erythromycin, clarithromycin, or azithromycin.
What is the appropriate duration of antimicrobial therapy
Recommendations by the AAP for CAP note that treatment courses of 10 days have been best studied, although shorter courses may be just as effective, particularly for mild disease managed on an outpatient basis.
When should children be hospitalized
Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He had no conflicts to declare. Email him at pdnews@mdedge.com.
End Tidal Capnography in the Emergency Department
Capnography is the measurement of the partial pressure of carbon dioxide (CO2) in exhaled air.1 It provides real-time information on ventilation (elimination of CO2), perfusion (CO2 transportation in vasculature), and metabolism (production of CO2 via cellular metabolism).2 The technology was originally developed in the 1970s to monitor general anesthesia patients; however, its reach has since broadened, with numerous applications currently in use and in development for the emergency provider (EP).3
Capnography exists in two configurations: a mainstream device that attaches directly to the hub of an endotracheal tube (ETT) and a side-stream device that measure levels via nasal or nasal-oral cannula.1,3
Qualitative monitors use a colorimetric device that monitors the end-tidal CO2 (EtCO2) in exhaled gas and changes color depending on the amount of CO2 present.2,4 Expired CO2 and H20 form carbonic acid, causing the specially treated litmus paper inside the device to change from purple to yellow.2,4 Quantitative monitors display a capnogram, the waveform of expired CO2 as a function of time; as well as the capnometer, which depicts the numerical EtCO2 for each breath.4 In this overview, we will discuss the general interpretation of capnography and its specific uses in the ED.
The Capnogram
Just like the various stages of an electrocardiogram represent different phases of the cardiac cycle, different phases of a capnogram correspond to different phases of the respiratory cycle. Knowing how to analyze and interpret each phase will contribute to the utility of capnography. While there has been considerable ambiguity in the terminology related to the capnogram,5-7 the most frequently referenced capnogram terminology consists of the following phases (Figure 1):
Phase I: represents beginning of exhalation, where the dead space is cleared from the upper airway.2 This should be zero unless the patient is rebreathing CO2-laden expired gas from either artificially increased dead space or hypoventilation.2,8 A precipitous rise in both the baseline and EtCO2 may indicate contamination of the sensor, such as with secretions or water vapor.2,6
Phase II: rapid rise in exhaled as the CO2 from the alveoli reaches the sensor.4 This rise should be steep, particularly when ventilation to perfusion (V/Q) is well matched. More V/Q heterogeneity, such as with COPD or asthma, leads to a more gradual slope.9 A more gradual phase 2 slope may also indicate a delay in CO2 delivery to the sampling site, such as with bronchospasm or ETT kinking.2
Phase III: the expiratory plateau, which represents the CO2 concentration approaching equilibrium from alveoli to nose. The plateau should be nearly horizontal.2 If all alveoli had the same pCO2, this plateau would be perfectly flat, but spatial and temporal mismatch in alveolar V/Q ratios result in variable exhaled CO2. When there is substantial V/Q heterogeneity, the slope of the plateau will increase.1,2,6
Phase IV: the initiation of inspiration, which should be a nearly vertical drop to a baseline. If prolonged or bleeding into the expiratory phase, consider a leak in the expiratory portion of the circuit, such as an ETT tube cuff leak.2
Phase 0: the inspiratory segment
Another important part of the capnogram is the alpha angle. This is the angle of transition between Phase II and Phase III. The combination of a prolonged phase II and steeper phase III leads to a more obtuse alpha angle and will have a “shark-fin” appearance to the capnogram. This suggests an obstructive process, such as asthma or COPD (Figure 2).1,2,6
Standard Uses
Intubation
Capnography, along with visualizing ETT placement through the vocal cords, is the standard of care for confirming correct placement during intubation.4,10,11 Alternative signs of endotracheal intubation, such as chest wall movement, auscultation, condensation of water vapor in the tube lumen, or pulse oximetry, are less accurate.12
While not ideal, correct ETT placement can be confirmed qualitatively using a colorimetric device.13 Upon correct placement, the resultant exhalation of CO2 will change the paper color from purple to yellow (indicating EtCO2 values > 15 mm Hg).2,4 Without this color change, tube placement should be verified to rule out esophageal intubation. Unfortunately, qualitative capnography has false positives and negatives that limit its utility in the ED, and this method should be avoided if quantitative capnography is available.
With quantitative capnography, obtaining the typical box-waveform on the capnogram reflects endotracheal intubation. In comparison, a flat capnogram is more indicative of an esophageal intubation (Figure 3).10 While other things may cause this waveform, such as technical malfunction or complete airway obstruction distal to the tube, tube placement confirmation to rule out esophageal intubation would be the first step to troubleshooting this waveform. In addition, if the ETT is placed in the hypopharynx above the vocal cords, the waveform may initially appear appropriate but will likely become erratic appearing over time.10
Quantitative capnography does have some limitations. For example, a main-stem bronchus intubation would still likely demonstrate normal-appearing capnography, so secondary strategies and a confirmatory chest x-ray are still indicated. False-negative ETCO2 readings can occur in low CO2 elimination states, such as cardiac arrest, pulmonary embolus, or pulmonary edema, while false-positives can theoretically occur after ingestion of large amounts of carbonated liquids or contamination of the sensor with stomach contents or acidic drugs.10 However, many of these misleading results can be caught by simply checking for an appropriate waveform.
Cardiac Arrest
Capnography has numerous uses in the monitoring, management, and prognostication of intubated patients in cardiac arrest.1,3,4,10,14 Under normal conditions, EtCO2 is 35-40 mm Hg. While the body still makes CO2 during cardiac arrest, it will not reach the alveoli without circulating blood.10 Without CPR, CO2 accumulates peripherally and won’t reach the lungs, causing EtCO2 to approach zero. This means that EtCO2 correlates directly with cardiac output during CPR, as long as ventilation remains constant.
This means the effectiveness of cardiac chest compression can be assessed in intubated patients using EtCO2, with higher values during CPR correlated with increased return of spontaneous circulation (ROSC) and survival.14-18 Using EtCO2 monitoring during cardiac arrest may improve outcomes,19 and the American Heart Association (AHA) recommends monitoring capnography during cardiac arrest to assess compression efficacy.10,20 EtCO2 >20 mm Hg is considered optimal, while EtCO2 <10-15 mm Hg is considered suboptimal.4,10,16 In a recent meta-analysis, the average EtCO2 was 13.1 mm Hg in those who did not obtain ROSC, compared to 25.8 mm Hg in those who did.21 As such, goal EtCO2 for effective compressions may be even higher in future recommendations. If EtCO2 is low, either compression technique should be improved or a different operator should do compressions. Every 1 cm increase in depth will increase EtCO2 by approximately 1.4 mm Hg.16 Interestingly, compression rate is not a significant predictor of EtCO2 over the dynamic range of chest compression delivery.16
An abrupt increase in EtCO2 is an early indicator of ROSC.10,14-16,22,23 A return of a perfusing rhythm will increase cardiac output. This allows for accumulated peripheral CO2 to reach the lungs, subsequently causing a rapid rise in EtCO2.24 It is important to note that when it comes to evaluating for ROSC, the actual numbers are less important than the change from pre- to post-ROSC. Providers should look for a jump of at least 10 mm Hg on capnometry.4 Nevertheless, an abrupt rise in EtCO2 is a non-sensitive marker for ROSC (33%, 95% CI 22-47% in one multicenter cross-sectional study), meaning that the lack of an abrupt rise of EtCO2 may not necessarily mean a lack of ROSC.23
The EtCO2 level may help guide decision-making in assessing whether continued resuscitation in cardiac arrest is futile. Values <10 mm Hg after 20 minutes of active resuscitation have consistently demonstrated minimal chance of survival.17,25,26 In one study, an EtCO2 of <10 mm Hg at 20 minutes had a sensitivity, specificity, PPV, and NPV of 100% for death in PEA arrest.17 However, determination of the specific EtCO2 cutoff and the timing is still an area of research with a final consensus pending.17,18,25-30 One recent study suggested that even 3 min with EtCO2 <10 mm Hg could be an appropriate cutoff to cease resuscitation efforts.27
Unfortunately, there is a large amount of heterogeneity in the available literature using capnography to assess for ROSC and in guiding resuscitation efforts. EtCO2 should not be used as the only factor in the determination to cease resuscitation. In addition, the AHA recommends that EtCO2 for prognostication should be limited to intubated patients only.20
It is important to note that while cardiac output is the largest factor for EtCO2 in arrest, other physiologic and iatrogenic causes may affect EtCO2 during resuscitation. For example, there is considerable variation in EtCO2 with changes in ventilation rate.4 Measured CO2 may be significantly lower with manual instead of mechanical ventilation, likely due to over-ventilation that not only reduces alveolar CO2 but also causes excess intra-thoracic pressure, reducing venous return.21 For these reasons, use caution when using EtCO2 during manual ventilation of an intubated patient in cardiac arrest. In addition, administration of epinephrine may cause a small decrease in EtCO2, although the effect may vary for each individual.10,31 Sodium bicarbonate can also cause a transient increase in CO2 due to its conversion into CO2 and H2O.10
Procedural Sedation
Capnography is being used with increasing frequency to monitor patients during procedural sedation; it is now considered standard of care in many settings.32 Although rare, hypoventilation is a risk of procedural sedation.33 Typically, respiratory depression during procedural sedation is diagnosed with non-invasive pulse oximetry and visual inspection.34 However, capnography has been shown to identify respiratory depression, airway obstruction, apnea, and laryngospasm earlier than pulse oximetry, allowing the provider to intervene quicker.34,35 Unlike pulse oximetry, the capnogram also remains stable during patient motion and is reliable in low-perfusion states.36
There are two distinct types of hypoventilation detected by capnography. Bradypneic hypoventilation (type 1), which is characterized by a decreased respiratory rate, results in a decreased expiratory time and a subsequent rise in EtCO2.36 This is depicted on capnography by a high EtCO2 and longer waveform, and is commonly observed after oversedation with opioids (Figure 4).36 In contrast, hypopneic hypoventilation (type 2) occurs with low tidal volumes but a normal respiratory rate.36 Type 2 is graphically represented by a suddenly lower ETCO2 with otherwise normal waveform and occurs most commonly with sedative-hypnotic drugs (Figure 5).36 Seeing either type during procedural sedation should alert the clinician to assess for airway obstruction, consider supplemental oxygen, cease drug administration or reduce dosing, and consider reversal if appropriate.36
There is some debate as to the utility of capnography for procedural sedation. While it is clear that capnography decreases the incidence of hypoxia, some studies suggest that it may not reduce patient-centered outcomes such as adverse respiratory events, neurologic injury, aspiration, or death compared to standard monitoring.35,37,38 However, pulse oximetry alone can suffer response delay, while EtCO2 can rapidly detect hypoventilation.39
Potential Uses/Applications
Respiratory Distress
Capnography can provide dynamic monitoring in patients with acute respiratory distress. Measuring EtCO2 with each breath provides instantaneous feedback on the clinical status of the patient and has numerous specific uses.1,3,4
Determining the etiology of respiratory distress in either the obtunded patient or those with multiple comorbidities can be a challenge. Vital sign abnormalities and physical exam findings can overlap in numerous conditions, which may only further obscure the diagnosis. Since different etiologies for respiratory disease require different management modalities, anything that can help clue in to the specific cause can be beneficial. As discussed above, obstructive diseases such as COPD or asthma demonstrate a “shark-fin appearance” on capnogram due to both V/Q heterogeneity and a prolonged expiratory phase due to airway constriction, which will contrast to the typical box-waveform in other conditions (Figure 2).1,2,6 Some studies have been able differentiate COPD from congestive heart failure (CHF) by waveform analysis alone, though this was primarily done via computer algorithms.40 Seeing the shark-fin (or the lack thereof) can help guide management of respiratory distress in conjunction with the remainder of the initial assessment.
Monitoring capnography can help with management and disposition in those with COPD or asthma. During exacerbations, EtCO2 levels may initially drop as the patient hyperventilates to compensate.1 It is not until ventilation becomes less effective that EtCO2 levels begin to rise. This may occur before hypoxia sets in and can prompt the clinician to escalate ventilation strategies. In addition, the normalization of the “shark-fin” obstructive pattern towards the more typical box-form wave may indicate effective treatment, though more data is needed before it can be recommended.41 One of the advantages of this technique would be that it is independent of patient effort, unlike peak-flow monitoring.
EtCO2 can be beneficial even before patients get to the ED. In one study, prehospital patients presenting with asthma or COPD who were found to have EtCO2 of >50 mm Hg or <28 mm Hg, representing the upper and lower limits in the study, had greater rates of intubation, critical care admission, and mortality.42 The patients in this cohort with higher EtCO2 were likely tiring after prolonged hyperventilation and therefore would be more likely to need ventilatory support. Those on the lower end were likely hyperventilating and had not yet tired out. It is important to note that while arrival EtCO2 levels may aid in determining the more critically ill, post-treatment levels were not found to have a statistical difference in determining disposition in patients with asthma or COPD.43
Caution is advised when attempting to use EtCO2 to approximate an arterial blood gas CO2 (PaCO2). While EtCO2 can correlate with PaCO2 within 5 mm Hg in greater than 80% of patients with dyspnea,44 large discrepancies are common depending on the disease state.45 In general, the EtCO2 should always be lower than the PaCO2 due to the contribution to the ETCO2 from dead space, which has a low CO2 content due to lack of perfusion.
Sepsis
EtCO2 may help identify septic patients given its inverse relationship with lactate levels.46-49 In conditions of poor tissue perfusion, lactate builds up. This begins to make the blood acidotic in the form of newly acquired anions, with a resultant anion gap metabolic acidosis. The body then tries to acutely compensate for this by hyperventilating, resulting in the observed lowering of EtCO2. Since lactate is a predictor of mortality in sepsis,50 and monitoring lactate clearance to evaluate resuscitation efforts in sepsis is recommended,51 EtCO2 could play a similar role. One group in particular has demonstrated that, when used with SIRS criteria, abnormally low prehospital EtCO2 levels is predictive of sepsis and inhospital mortality, and is more predictive than SIRS criteria alone.48,50 That said, EtCO2 was not associated with lactate temporally at 3 and 6 hours,51 so it should not be used to guide resuscitation like a lactate clearance. It appears that EtCO2 may be helpful for triage in sepsis, but more study is needed to determine the exact role particularly given most of the available research involves multiple studies from one group.47,48,52
Diabetic Ketoacidosis
Initial bicarbonate levels and venous pH are associated with low EtCO2 readings in diabetic ketoacidosis (DKA).54,55 This could have many practical uses, in particular for patients presenting with hyperglycemia to rule out DKA. One study demonstrated that a blood glucose >250 mg/dL and capnography of >24.5 mm Hg had 90% sensitivity for excluding DKA.55 A value of 35 mm Hg or greater demonstrated 100% sensitivity for excluding DKA in patients with initial glucose >550 mg/dL,56 though this blood glucose is not practical, as this excludes many patients the EP would seek to rule out DKA (recall that blood glucose only has to be >250 mg/dL for the diagnosis). Smaller studies focused on the pediatric population found a 100% sensitivity marker for DKA varied from >30 to >36 mm Hg.57,58 Clearly a role exists, but no study has demonstrated sufficient sensitivity for ruling out DKA with EtCO2 and blood glucose alone within the framework of clinically relevant values.
Trauma
As described above, low EtCO2 is inversely correlated with lactate.46 Because of this, it could theoretically be a marker of hypoperfusion in trauma. Initial EtCO2 values <25 mm Hg have been associated with mortality and hemorrhage in intubated trauma patients,59 as well as mortality prior to discharge in nonintubated trauma patients.60 However, it did not demonstrate added clinical utility when combined with Glasgow Coma Scale (GCS) score, systolic blood pressure, and age in predicting severe injury.61
Pulmonary Embolism
A pulmonary embolism (PE) causes a blockage in blood flow to alveoli, which results in a decrease in CO2 transportation to the alveoli and thus lower EtCO2, while also widening the gradient between PaCO2 and EtCO2.37 Because of this, it has a theoretical role in the diagnosis of PE, though numerous studies have demonstrated that EtCO2 alone is not sensitive nor specific enough for this role.62-66 In a recent meta-analysis, a pretest probability of 10% could lead to a posttest probability of 3% using capnography.62 While further study is needed before recommendation, this indicates that capnography could obviate the need for imaging in low to intermediate risk patients either after a positive D-Dimer or instead of obtaining a D-dimer.62-64
Triage
Simply measuring an initial EtCO2 as a triage vital sign may have added benefit to the EP, and consideration could be made for making this a policy in your ED. One study demonstrated that abnormal initial EtCO2 (outside of 35-45 mm Hg) was predictive of admisison (RR 2.5, 95% CI 1.5-4.0).67 An abnormal EtCO2 (outside of 31-41 mm Hg for this study) was 93% sensitive (95% CI 79-98%), with expectedly low specificity of 44% (95% CI 41-48%) for mortality prior to discharge.47 This potential vital sign may be treated similarly to tachycardia; while an abnormal heart rate should increase a clinician’s concern for a pathological condition, it needs to be taken in context of the situation to accurately interpret it.
Summary
Capnography has numerous uses in the ED in both intubated and spontaneously breathing patients. Quantitative capnography is the standard of care for confirming endotracheal intubation. It is recommended as an aide in maximizing chest compressions during cardiac arrest and can assist in prognostication. It rapidly identifies hypoventilation during procedural sedation. It also has many more potential applications that continue to be explored in areas such as respiratory distress, sepsis, trauma, DKA, and PE. Ultimately, capnography should always be used in association with the remainder of the clinical assessment.
- Manifold CA, Davids B, Villers LC, Wampler DA. Capnography for the nonintubated patient in the emergency setting. J Emerg Med. 2013;45(4):626-632.
- Ward K, Yealy DM. End-tidal carbon dioxide monitoring in emergency medicine, part 1: basic principles. Acad Emerg Med. 1998;5(6):628-636.
- Krauss B, Falk JL. Carbon dioxide monitoring (capnography). UpToDate. Waltham MA: UpToDate Inc. www.uptodate.com.
- Long B, Koyfman A, Michael AV. Capnography in the emergency department: a review of uses, waveforms, and limitations. J Emerg Med. 2017;(53)6:829-842.
- Shankar Kodali B. Capnography: A Comprehensive Educational Website. Boston, MA. www.capnography.com.
- Kodali B. Capnography outside the operating room. Anesthesiology. 2013;118:192-201.
- Bhavani, S. Defining segments and phases of a time capnogram. Anesth Analg. 2000;91(4):973-977.
- Petersson J, Glenny R. Gas exchange and ventilation-perfusion relationships in the lung. Eur Resp J. 2014;44(4):1023-1041.
- Nassar B, Schmidt GA. Capnography during critical illness. Chest. 2016;149(2):576-585.
- Neumar RW, Otto CW, Link MS, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 suppl 3):S729-S767.
- Burns SM, Carpenter R, Blevins C, Bragg S, Marshall M, Browne L, et al. Detection of inadvertent airway intubation during gastric tube insertion: capnography versus a colorimetric carbon dioxide detector. Am J Crit Care. 2006:15(2):188-195.
- Goldberg JS, Rawle PR, Zehnder JL, Sladen RN. Colorimetric end-tidal carbon dioxide monitoring for tracheal intubation. Anesthesia and analgesia. 1990:70(2):191-194.
- O'Flaherty D, Adams AP. The end-tidal carbon dioxide detector: assessment of a new method to distinguish oesophageal from tracheal intubation. Anaesthesia. 1990:45(8):653-655.
- Garnett AR, Ornato JP, Gonzalez ER, Johnson EB. End-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. JAMA. 1987;257:512-515.
- Falk JL, Rackow EC, Weil MH. End-tidal carbon dioxide concentration during cardiopulmonary resuscitation. N Engl J Med. 1988;318(10):607-611.
- Sheak KR, Wiebe DJ, Leary M, Babaeizadeh S, Yuen TC, Zive D, et al. Quantitative relationship between end-tidal carbon dioxide and CPR quality during both in-hospital and out-of-hospital cardiac arrest. Resuscitation. 2015;89:149-154.
- Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med. 1997;337(5):301-306.
- Touma O, Davies M. The prognostic value of end tidal carbon dioxide during cardiac arrest: a systematic review. Resuscitation. 2013;84(11):1470-1479.
- Chen JJ, Lee YK, Hou SW, et al. End-tidal carbon dioxide monitoring may be associated with a higher possibility of return of spontaneous circulation during out-of-hospital cardiac arrest: a population-based study. Scan J Trauma Resusc Emerg Med. 2015;23:104.
- Neumar RW, Shuster M, Callaway CW et al. Part 7: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(suppl 2):S315-S367.
- Hartmann SW, Farris RW, Di Gennaro JL, Roberts JS. Systematic review and meta-analysis of end-tidal carbon dioxide values associated with return of spontaneous circulation during cardiopulmonary resuscitation. J Intensive Care Med. 2015;(30):426-435.
- Eckstein, M, Hatch, L, Malleck, J et al. EtCO2 as a predictor of survival in out-of hospital cardiac arrest. Prehosp Disaster Med. 2016;104:53-58.
- Lui CT, Poon KM, Tsui KL. Abrupt rise of end tidal carbon dioxide was a specific but non-sensitive marker of return of spontaneous circulation with out-of-hospital cardiac arrest. Resuscitation. 2016;104:53-58.
- Pokorna M, Necas E, Kratochvil J et al. A sudden increase in partial pressure end-tidal carbon dioxide at the moment of return of spontaneous circulation. J Emerg Med. 2010;38:614-621.
- Sanders A, Kern K, Otto C, et al. End-tidal carbon dixoide monitoring during cardiopulmonary resuscitation: a prognostic indicator for survival. JAMA. 1989;262:1347-1351.
- Wayne M, Levine R, And Miller C. Use of end-tidal carbon dioxide to predict outcome in prehospital cardiac arrest. Ann Emerg Med. 1995;25(6):762-767.
- Poon KM, Lui CT, Tsui KL. Prognostication of out-of-hopsital cardiac arrest patients by 3-min end-tidal capnometry level in emergency department. Resuscitation. 2016;102:80-84.
- Einav S, Bromiker R, Weiniger C, Matot I. Mathematical modeling for prediction of survival from resuscitation based on computerized continuous capnography: proof of concept. Acad Emerg Med. 2011;18:468-475.
- Pearce A, Davis D, Minokadeh A, Sell R. Initial end-tidal carbon dioxide as a prognostic indicator for inpatient PEA arrest. Resuscitation. 2015;92:77-81.
- Akinci, E, Ramadan H, Yuzbasioglu Y, Coksun F. Comparison of end-tidal carbon dioxide levels with cardiopulmonary resuscitation success presented to emergency department with cardiopulmonary arrest. Pak J Med Sci. 2014;30(1):16-21.
- Callaham M, Barton C, Matthay M. Effect of epinephrine on the ability of end-tidal carbon dioxide readings to predict initial resuscitation from cardiac arrest. Crit Care Med. 1992; 20:337-343.
- Wall BF, Magee K, Campbell SG, Zed PJ. Capnography versus standard monitoring for emergency department procedural sedation and analgesia. Cochrane Database of Systematic Reviews. 2017(3).
- Langhan ML, Shabanova V, Li FY, Bernstein SL, Shapiro ED. A randomized controlled trial of capnography during sedation in a pediatric emergency setting. Am J Emerg Med. 2015;33(1):25-30.
- Campbell SG, Magee KD, Zed PJ, Froese P, Etsell G, LaPierre A et al. End-tidal capnometry during emergency department procedural sedation and analgesia: a randomized, controlled study. World J Emerg Med. 2016;7(1):13.
- Waugh JB, Epps CA, Khodneva YA. Capnography enhances surveillance of respiratory events during procedural sedation: a meta-analysis. J Clin Anesth. 2011;23(3):189-196.
- Krauss B, Hess DR. Capnography for procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2007;50(2):172-181.
- Deitch K, Miner J, Chudnofsky CR, Dominici P, Latta D. Does end tidal CO2 monitoring during emergency department procedural sedation and analgesia with propofol decrease the incidence of hypoxic events? A randomized, controlled trial. Ann Emerg Med. 2010;55(3):258-264.
- Godwin SA, Caro DA, Wolf SJ, Jagoda AS, Charles R, Marett BE, Moore J. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2005;45(2):177-196.
- Hamber EA, Bailey PI, James SW et al. Delays in the detection of hypoxemia due to site of pulse oximetry pulse placement. J Clin Anesth. 1999;11:113-118.
- Mieloszyk RJ, Vergehese GC, Deitch K, et al. Automated quantitative analysis of capnogram shape for COPD-normal and COPD-CHF classification. IEEE Trans Biomed Eng. 2014;61:2882-2890.
- Howe TA, Jaalam K, R. Ahmad, Sheng CK, Ab Rahman NHN. The use of end-tidal capnography to monitor non-intubated patients presenting with acute exacerbation of asthma in the emergency department. J Emerg Med. 2011:41:581-589.
- Nagurka R, Bechmann S, Gluckman W et al. Utility of initial prehospital end-tidal carbon dioxide measurements to predict poor outcomes in adult asthmatic patients. Prehospital Emerg Care. 2014;18:180-184.
- Doğan NÖ, Şener A, Günaydın GP, İçme F, Çelik GK, Kavaklı HŞ, Temrel TA. The accuracy of mainstream end-tidal carbon dioxide levels to predict the severity of chronic obstructive pulmonary disease exacerbations presented to the ED. Am J Emerg Med. 2014;32(5):408-411.
- Cinar O, Acar YA, Arziman I, et al. Can mainstream end-tidal carbon dioxide measurement accurately predict the arterial carbon dioxide levels of patients with acute dyspnea in ED. Am J Emerg Med. 2012;30:358-361.
- Nassar BS, Schmidt GA. Capnography during critical illness. Chest. 2016:149(2):576-585.
- Caputo ND, Fraser RM, Paliga A et al. Nasal cannula end-tidal CO2 correlates with serum lactate levels and odds of operative intervention in penetrating trauma patients: a prospective cohort study. J Trauma Acute Care Surg. 2012;73:1202-1207.
- Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. 2014;32(2):160-165.
- Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. 2013;31(1):64-71.
- McGillicuddy DC, Tang A, Cataldo L, et al. Evaluation of end-tidal carbon dioxide role in predicting elevated SOFA and lactic acidosis. Intern Emerg Med. 2009;4:41-44.
- Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005;45:524-528.
- Levy, MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med. 2018;46:997-1000.
- Hunter CL, Silvestri S, Ralls G et al. A prehospital screening tool utilizing end-tidal carbon dioxide predicts sepsis and severe sepsis. Am J Emerg Med. 2016;34:813-819.
- Guirgis FW, Williams DJ, Kalynych CJ, Hardy ME, Jones AE, Dodani S, Wears RL. End-tidal carbon dioxide as a goal of early sepsis therapy. Am J Emerg Med. 2014;32(11):1351-1356.
- Kartal M, Eray O, Rinnert S, Gosku E, Bektas F, Eken C. ETCO2: a predictive tool for excluding metabolic disturbances in nonintubated patients. Am J Emerg Med. 2011;29: 65-69.
- Solmeinpur H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for diagnosis in patients with suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. 2013;14:590-594.
- Bou Chebl R, Madden B, Belsky J, Harmouche E, Yessayan L. Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. BMC Emerg Med. 2016;16:7.
- Fearon DM, Steele DW. End-tidal carbon dioxide predicts the presence and severity of acidosis in children with diabetes. Acad Emerg Med. 2002;9:1373-1378.
- Gilhotra Y, Porter P. Predicting diabetic ketoacidosis in children by measuring end-tidal CO2 via non-invasive nasal capnography. J Paediatr Child Health. 2007;43:677-680.
- Dunham CM, Chirichella TJ, Gruber BS, et al. In emergently ventilated trauma patients, low end-tidal CO2 and low cardiac output are associated and correlate with hemodynamic instability, hemorrhage, abnormal pupils, and death. BMC Anesthesiol. 2013;13-20.
- Deakin CD, Sado DM, Coats TJ, Davies G. Prehospital end-tidal carbon dioxide concentration and outcome in major trauma. J Trauma.2004;57:65-68.
- Williams DJ, Guirgis FW, Morrissey TK, Wilkerson J, Wears RL, Kalynych C, Kerwin AJ, Godwin SA. End-tidal carbon dioxide and occult injury in trauma patients: ETCO2 does not rule out severe injury. Am J Emerg Med. 2016;34(11):2146-2149.
- Manara A, D’hoore W, Thys F. Capnography as a diagnostic tool for pulmonary embolism: a meta-analysis. Ann Emerg Med. 2013;52:584-591.
- Yoon YH, Lee SW, Jung DM et al. The additional use of end-tidal alveolar dead space fraction following D-dimer test to improve diagnostic accuracy for pulmonary embolism in the emergency department. Emerg Med J. 2010;27:663-667.
- Hemnes AR, Newman AL, Rosenbaum B, et al. Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism. Eur Resp J. 2010;35:735-741.
- Rias I Jacob B. Pulmonary embolism in Bradford, UK: role of end-tidal CO2 as a screening tool. Clin Med (Lond). 2014;14:128-133.
- Yuksel M, Pekdemir M, Yilmaz S, et al. Diagnostic accuracy of noninvasive end-tidal carbon dioxide measurement in emergency department patients with suspected pulmonary embolism. Turk J Med Sci. 2016;46:84–90.
- Williams D, Morrissey T, Caro D, Wears R, Kalynyc C. Side-stream qunatitative end-tidal carbon dioxide measurement as a triage tool in emergency medicine. Ann Emerg Med. 2011;58:S212-S213.
Capnography is the measurement of the partial pressure of carbon dioxide (CO2) in exhaled air.1 It provides real-time information on ventilation (elimination of CO2), perfusion (CO2 transportation in vasculature), and metabolism (production of CO2 via cellular metabolism).2 The technology was originally developed in the 1970s to monitor general anesthesia patients; however, its reach has since broadened, with numerous applications currently in use and in development for the emergency provider (EP).3
Capnography exists in two configurations: a mainstream device that attaches directly to the hub of an endotracheal tube (ETT) and a side-stream device that measure levels via nasal or nasal-oral cannula.1,3
Qualitative monitors use a colorimetric device that monitors the end-tidal CO2 (EtCO2) in exhaled gas and changes color depending on the amount of CO2 present.2,4 Expired CO2 and H20 form carbonic acid, causing the specially treated litmus paper inside the device to change from purple to yellow.2,4 Quantitative monitors display a capnogram, the waveform of expired CO2 as a function of time; as well as the capnometer, which depicts the numerical EtCO2 for each breath.4 In this overview, we will discuss the general interpretation of capnography and its specific uses in the ED.
The Capnogram
Just like the various stages of an electrocardiogram represent different phases of the cardiac cycle, different phases of a capnogram correspond to different phases of the respiratory cycle. Knowing how to analyze and interpret each phase will contribute to the utility of capnography. While there has been considerable ambiguity in the terminology related to the capnogram,5-7 the most frequently referenced capnogram terminology consists of the following phases (Figure 1):
Phase I: represents beginning of exhalation, where the dead space is cleared from the upper airway.2 This should be zero unless the patient is rebreathing CO2-laden expired gas from either artificially increased dead space or hypoventilation.2,8 A precipitous rise in both the baseline and EtCO2 may indicate contamination of the sensor, such as with secretions or water vapor.2,6
Phase II: rapid rise in exhaled as the CO2 from the alveoli reaches the sensor.4 This rise should be steep, particularly when ventilation to perfusion (V/Q) is well matched. More V/Q heterogeneity, such as with COPD or asthma, leads to a more gradual slope.9 A more gradual phase 2 slope may also indicate a delay in CO2 delivery to the sampling site, such as with bronchospasm or ETT kinking.2
Phase III: the expiratory plateau, which represents the CO2 concentration approaching equilibrium from alveoli to nose. The plateau should be nearly horizontal.2 If all alveoli had the same pCO2, this plateau would be perfectly flat, but spatial and temporal mismatch in alveolar V/Q ratios result in variable exhaled CO2. When there is substantial V/Q heterogeneity, the slope of the plateau will increase.1,2,6
Phase IV: the initiation of inspiration, which should be a nearly vertical drop to a baseline. If prolonged or bleeding into the expiratory phase, consider a leak in the expiratory portion of the circuit, such as an ETT tube cuff leak.2
Phase 0: the inspiratory segment
Another important part of the capnogram is the alpha angle. This is the angle of transition between Phase II and Phase III. The combination of a prolonged phase II and steeper phase III leads to a more obtuse alpha angle and will have a “shark-fin” appearance to the capnogram. This suggests an obstructive process, such as asthma or COPD (Figure 2).1,2,6
Standard Uses
Intubation
Capnography, along with visualizing ETT placement through the vocal cords, is the standard of care for confirming correct placement during intubation.4,10,11 Alternative signs of endotracheal intubation, such as chest wall movement, auscultation, condensation of water vapor in the tube lumen, or pulse oximetry, are less accurate.12
While not ideal, correct ETT placement can be confirmed qualitatively using a colorimetric device.13 Upon correct placement, the resultant exhalation of CO2 will change the paper color from purple to yellow (indicating EtCO2 values > 15 mm Hg).2,4 Without this color change, tube placement should be verified to rule out esophageal intubation. Unfortunately, qualitative capnography has false positives and negatives that limit its utility in the ED, and this method should be avoided if quantitative capnography is available.
With quantitative capnography, obtaining the typical box-waveform on the capnogram reflects endotracheal intubation. In comparison, a flat capnogram is more indicative of an esophageal intubation (Figure 3).10 While other things may cause this waveform, such as technical malfunction or complete airway obstruction distal to the tube, tube placement confirmation to rule out esophageal intubation would be the first step to troubleshooting this waveform. In addition, if the ETT is placed in the hypopharynx above the vocal cords, the waveform may initially appear appropriate but will likely become erratic appearing over time.10
Quantitative capnography does have some limitations. For example, a main-stem bronchus intubation would still likely demonstrate normal-appearing capnography, so secondary strategies and a confirmatory chest x-ray are still indicated. False-negative ETCO2 readings can occur in low CO2 elimination states, such as cardiac arrest, pulmonary embolus, or pulmonary edema, while false-positives can theoretically occur after ingestion of large amounts of carbonated liquids or contamination of the sensor with stomach contents or acidic drugs.10 However, many of these misleading results can be caught by simply checking for an appropriate waveform.
Cardiac Arrest
Capnography has numerous uses in the monitoring, management, and prognostication of intubated patients in cardiac arrest.1,3,4,10,14 Under normal conditions, EtCO2 is 35-40 mm Hg. While the body still makes CO2 during cardiac arrest, it will not reach the alveoli without circulating blood.10 Without CPR, CO2 accumulates peripherally and won’t reach the lungs, causing EtCO2 to approach zero. This means that EtCO2 correlates directly with cardiac output during CPR, as long as ventilation remains constant.
This means the effectiveness of cardiac chest compression can be assessed in intubated patients using EtCO2, with higher values during CPR correlated with increased return of spontaneous circulation (ROSC) and survival.14-18 Using EtCO2 monitoring during cardiac arrest may improve outcomes,19 and the American Heart Association (AHA) recommends monitoring capnography during cardiac arrest to assess compression efficacy.10,20 EtCO2 >20 mm Hg is considered optimal, while EtCO2 <10-15 mm Hg is considered suboptimal.4,10,16 In a recent meta-analysis, the average EtCO2 was 13.1 mm Hg in those who did not obtain ROSC, compared to 25.8 mm Hg in those who did.21 As such, goal EtCO2 for effective compressions may be even higher in future recommendations. If EtCO2 is low, either compression technique should be improved or a different operator should do compressions. Every 1 cm increase in depth will increase EtCO2 by approximately 1.4 mm Hg.16 Interestingly, compression rate is not a significant predictor of EtCO2 over the dynamic range of chest compression delivery.16
An abrupt increase in EtCO2 is an early indicator of ROSC.10,14-16,22,23 A return of a perfusing rhythm will increase cardiac output. This allows for accumulated peripheral CO2 to reach the lungs, subsequently causing a rapid rise in EtCO2.24 It is important to note that when it comes to evaluating for ROSC, the actual numbers are less important than the change from pre- to post-ROSC. Providers should look for a jump of at least 10 mm Hg on capnometry.4 Nevertheless, an abrupt rise in EtCO2 is a non-sensitive marker for ROSC (33%, 95% CI 22-47% in one multicenter cross-sectional study), meaning that the lack of an abrupt rise of EtCO2 may not necessarily mean a lack of ROSC.23
The EtCO2 level may help guide decision-making in assessing whether continued resuscitation in cardiac arrest is futile. Values <10 mm Hg after 20 minutes of active resuscitation have consistently demonstrated minimal chance of survival.17,25,26 In one study, an EtCO2 of <10 mm Hg at 20 minutes had a sensitivity, specificity, PPV, and NPV of 100% for death in PEA arrest.17 However, determination of the specific EtCO2 cutoff and the timing is still an area of research with a final consensus pending.17,18,25-30 One recent study suggested that even 3 min with EtCO2 <10 mm Hg could be an appropriate cutoff to cease resuscitation efforts.27
Unfortunately, there is a large amount of heterogeneity in the available literature using capnography to assess for ROSC and in guiding resuscitation efforts. EtCO2 should not be used as the only factor in the determination to cease resuscitation. In addition, the AHA recommends that EtCO2 for prognostication should be limited to intubated patients only.20
It is important to note that while cardiac output is the largest factor for EtCO2 in arrest, other physiologic and iatrogenic causes may affect EtCO2 during resuscitation. For example, there is considerable variation in EtCO2 with changes in ventilation rate.4 Measured CO2 may be significantly lower with manual instead of mechanical ventilation, likely due to over-ventilation that not only reduces alveolar CO2 but also causes excess intra-thoracic pressure, reducing venous return.21 For these reasons, use caution when using EtCO2 during manual ventilation of an intubated patient in cardiac arrest. In addition, administration of epinephrine may cause a small decrease in EtCO2, although the effect may vary for each individual.10,31 Sodium bicarbonate can also cause a transient increase in CO2 due to its conversion into CO2 and H2O.10
Procedural Sedation
Capnography is being used with increasing frequency to monitor patients during procedural sedation; it is now considered standard of care in many settings.32 Although rare, hypoventilation is a risk of procedural sedation.33 Typically, respiratory depression during procedural sedation is diagnosed with non-invasive pulse oximetry and visual inspection.34 However, capnography has been shown to identify respiratory depression, airway obstruction, apnea, and laryngospasm earlier than pulse oximetry, allowing the provider to intervene quicker.34,35 Unlike pulse oximetry, the capnogram also remains stable during patient motion and is reliable in low-perfusion states.36
There are two distinct types of hypoventilation detected by capnography. Bradypneic hypoventilation (type 1), which is characterized by a decreased respiratory rate, results in a decreased expiratory time and a subsequent rise in EtCO2.36 This is depicted on capnography by a high EtCO2 and longer waveform, and is commonly observed after oversedation with opioids (Figure 4).36 In contrast, hypopneic hypoventilation (type 2) occurs with low tidal volumes but a normal respiratory rate.36 Type 2 is graphically represented by a suddenly lower ETCO2 with otherwise normal waveform and occurs most commonly with sedative-hypnotic drugs (Figure 5).36 Seeing either type during procedural sedation should alert the clinician to assess for airway obstruction, consider supplemental oxygen, cease drug administration or reduce dosing, and consider reversal if appropriate.36
There is some debate as to the utility of capnography for procedural sedation. While it is clear that capnography decreases the incidence of hypoxia, some studies suggest that it may not reduce patient-centered outcomes such as adverse respiratory events, neurologic injury, aspiration, or death compared to standard monitoring.35,37,38 However, pulse oximetry alone can suffer response delay, while EtCO2 can rapidly detect hypoventilation.39
Potential Uses/Applications
Respiratory Distress
Capnography can provide dynamic monitoring in patients with acute respiratory distress. Measuring EtCO2 with each breath provides instantaneous feedback on the clinical status of the patient and has numerous specific uses.1,3,4
Determining the etiology of respiratory distress in either the obtunded patient or those with multiple comorbidities can be a challenge. Vital sign abnormalities and physical exam findings can overlap in numerous conditions, which may only further obscure the diagnosis. Since different etiologies for respiratory disease require different management modalities, anything that can help clue in to the specific cause can be beneficial. As discussed above, obstructive diseases such as COPD or asthma demonstrate a “shark-fin appearance” on capnogram due to both V/Q heterogeneity and a prolonged expiratory phase due to airway constriction, which will contrast to the typical box-waveform in other conditions (Figure 2).1,2,6 Some studies have been able differentiate COPD from congestive heart failure (CHF) by waveform analysis alone, though this was primarily done via computer algorithms.40 Seeing the shark-fin (or the lack thereof) can help guide management of respiratory distress in conjunction with the remainder of the initial assessment.
Monitoring capnography can help with management and disposition in those with COPD or asthma. During exacerbations, EtCO2 levels may initially drop as the patient hyperventilates to compensate.1 It is not until ventilation becomes less effective that EtCO2 levels begin to rise. This may occur before hypoxia sets in and can prompt the clinician to escalate ventilation strategies. In addition, the normalization of the “shark-fin” obstructive pattern towards the more typical box-form wave may indicate effective treatment, though more data is needed before it can be recommended.41 One of the advantages of this technique would be that it is independent of patient effort, unlike peak-flow monitoring.
EtCO2 can be beneficial even before patients get to the ED. In one study, prehospital patients presenting with asthma or COPD who were found to have EtCO2 of >50 mm Hg or <28 mm Hg, representing the upper and lower limits in the study, had greater rates of intubation, critical care admission, and mortality.42 The patients in this cohort with higher EtCO2 were likely tiring after prolonged hyperventilation and therefore would be more likely to need ventilatory support. Those on the lower end were likely hyperventilating and had not yet tired out. It is important to note that while arrival EtCO2 levels may aid in determining the more critically ill, post-treatment levels were not found to have a statistical difference in determining disposition in patients with asthma or COPD.43
Caution is advised when attempting to use EtCO2 to approximate an arterial blood gas CO2 (PaCO2). While EtCO2 can correlate with PaCO2 within 5 mm Hg in greater than 80% of patients with dyspnea,44 large discrepancies are common depending on the disease state.45 In general, the EtCO2 should always be lower than the PaCO2 due to the contribution to the ETCO2 from dead space, which has a low CO2 content due to lack of perfusion.
Sepsis
EtCO2 may help identify septic patients given its inverse relationship with lactate levels.46-49 In conditions of poor tissue perfusion, lactate builds up. This begins to make the blood acidotic in the form of newly acquired anions, with a resultant anion gap metabolic acidosis. The body then tries to acutely compensate for this by hyperventilating, resulting in the observed lowering of EtCO2. Since lactate is a predictor of mortality in sepsis,50 and monitoring lactate clearance to evaluate resuscitation efforts in sepsis is recommended,51 EtCO2 could play a similar role. One group in particular has demonstrated that, when used with SIRS criteria, abnormally low prehospital EtCO2 levels is predictive of sepsis and inhospital mortality, and is more predictive than SIRS criteria alone.48,50 That said, EtCO2 was not associated with lactate temporally at 3 and 6 hours,51 so it should not be used to guide resuscitation like a lactate clearance. It appears that EtCO2 may be helpful for triage in sepsis, but more study is needed to determine the exact role particularly given most of the available research involves multiple studies from one group.47,48,52
Diabetic Ketoacidosis
Initial bicarbonate levels and venous pH are associated with low EtCO2 readings in diabetic ketoacidosis (DKA).54,55 This could have many practical uses, in particular for patients presenting with hyperglycemia to rule out DKA. One study demonstrated that a blood glucose >250 mg/dL and capnography of >24.5 mm Hg had 90% sensitivity for excluding DKA.55 A value of 35 mm Hg or greater demonstrated 100% sensitivity for excluding DKA in patients with initial glucose >550 mg/dL,56 though this blood glucose is not practical, as this excludes many patients the EP would seek to rule out DKA (recall that blood glucose only has to be >250 mg/dL for the diagnosis). Smaller studies focused on the pediatric population found a 100% sensitivity marker for DKA varied from >30 to >36 mm Hg.57,58 Clearly a role exists, but no study has demonstrated sufficient sensitivity for ruling out DKA with EtCO2 and blood glucose alone within the framework of clinically relevant values.
Trauma
As described above, low EtCO2 is inversely correlated with lactate.46 Because of this, it could theoretically be a marker of hypoperfusion in trauma. Initial EtCO2 values <25 mm Hg have been associated with mortality and hemorrhage in intubated trauma patients,59 as well as mortality prior to discharge in nonintubated trauma patients.60 However, it did not demonstrate added clinical utility when combined with Glasgow Coma Scale (GCS) score, systolic blood pressure, and age in predicting severe injury.61
Pulmonary Embolism
A pulmonary embolism (PE) causes a blockage in blood flow to alveoli, which results in a decrease in CO2 transportation to the alveoli and thus lower EtCO2, while also widening the gradient between PaCO2 and EtCO2.37 Because of this, it has a theoretical role in the diagnosis of PE, though numerous studies have demonstrated that EtCO2 alone is not sensitive nor specific enough for this role.62-66 In a recent meta-analysis, a pretest probability of 10% could lead to a posttest probability of 3% using capnography.62 While further study is needed before recommendation, this indicates that capnography could obviate the need for imaging in low to intermediate risk patients either after a positive D-Dimer or instead of obtaining a D-dimer.62-64
Triage
Simply measuring an initial EtCO2 as a triage vital sign may have added benefit to the EP, and consideration could be made for making this a policy in your ED. One study demonstrated that abnormal initial EtCO2 (outside of 35-45 mm Hg) was predictive of admisison (RR 2.5, 95% CI 1.5-4.0).67 An abnormal EtCO2 (outside of 31-41 mm Hg for this study) was 93% sensitive (95% CI 79-98%), with expectedly low specificity of 44% (95% CI 41-48%) for mortality prior to discharge.47 This potential vital sign may be treated similarly to tachycardia; while an abnormal heart rate should increase a clinician’s concern for a pathological condition, it needs to be taken in context of the situation to accurately interpret it.
Summary
Capnography has numerous uses in the ED in both intubated and spontaneously breathing patients. Quantitative capnography is the standard of care for confirming endotracheal intubation. It is recommended as an aide in maximizing chest compressions during cardiac arrest and can assist in prognostication. It rapidly identifies hypoventilation during procedural sedation. It also has many more potential applications that continue to be explored in areas such as respiratory distress, sepsis, trauma, DKA, and PE. Ultimately, capnography should always be used in association with the remainder of the clinical assessment.
Capnography is the measurement of the partial pressure of carbon dioxide (CO2) in exhaled air.1 It provides real-time information on ventilation (elimination of CO2), perfusion (CO2 transportation in vasculature), and metabolism (production of CO2 via cellular metabolism).2 The technology was originally developed in the 1970s to monitor general anesthesia patients; however, its reach has since broadened, with numerous applications currently in use and in development for the emergency provider (EP).3
Capnography exists in two configurations: a mainstream device that attaches directly to the hub of an endotracheal tube (ETT) and a side-stream device that measure levels via nasal or nasal-oral cannula.1,3
Qualitative monitors use a colorimetric device that monitors the end-tidal CO2 (EtCO2) in exhaled gas and changes color depending on the amount of CO2 present.2,4 Expired CO2 and H20 form carbonic acid, causing the specially treated litmus paper inside the device to change from purple to yellow.2,4 Quantitative monitors display a capnogram, the waveform of expired CO2 as a function of time; as well as the capnometer, which depicts the numerical EtCO2 for each breath.4 In this overview, we will discuss the general interpretation of capnography and its specific uses in the ED.
The Capnogram
Just like the various stages of an electrocardiogram represent different phases of the cardiac cycle, different phases of a capnogram correspond to different phases of the respiratory cycle. Knowing how to analyze and interpret each phase will contribute to the utility of capnography. While there has been considerable ambiguity in the terminology related to the capnogram,5-7 the most frequently referenced capnogram terminology consists of the following phases (Figure 1):
Phase I: represents beginning of exhalation, where the dead space is cleared from the upper airway.2 This should be zero unless the patient is rebreathing CO2-laden expired gas from either artificially increased dead space or hypoventilation.2,8 A precipitous rise in both the baseline and EtCO2 may indicate contamination of the sensor, such as with secretions or water vapor.2,6
Phase II: rapid rise in exhaled as the CO2 from the alveoli reaches the sensor.4 This rise should be steep, particularly when ventilation to perfusion (V/Q) is well matched. More V/Q heterogeneity, such as with COPD or asthma, leads to a more gradual slope.9 A more gradual phase 2 slope may also indicate a delay in CO2 delivery to the sampling site, such as with bronchospasm or ETT kinking.2
Phase III: the expiratory plateau, which represents the CO2 concentration approaching equilibrium from alveoli to nose. The plateau should be nearly horizontal.2 If all alveoli had the same pCO2, this plateau would be perfectly flat, but spatial and temporal mismatch in alveolar V/Q ratios result in variable exhaled CO2. When there is substantial V/Q heterogeneity, the slope of the plateau will increase.1,2,6
Phase IV: the initiation of inspiration, which should be a nearly vertical drop to a baseline. If prolonged or bleeding into the expiratory phase, consider a leak in the expiratory portion of the circuit, such as an ETT tube cuff leak.2
Phase 0: the inspiratory segment
Another important part of the capnogram is the alpha angle. This is the angle of transition between Phase II and Phase III. The combination of a prolonged phase II and steeper phase III leads to a more obtuse alpha angle and will have a “shark-fin” appearance to the capnogram. This suggests an obstructive process, such as asthma or COPD (Figure 2).1,2,6
Standard Uses
Intubation
Capnography, along with visualizing ETT placement through the vocal cords, is the standard of care for confirming correct placement during intubation.4,10,11 Alternative signs of endotracheal intubation, such as chest wall movement, auscultation, condensation of water vapor in the tube lumen, or pulse oximetry, are less accurate.12
While not ideal, correct ETT placement can be confirmed qualitatively using a colorimetric device.13 Upon correct placement, the resultant exhalation of CO2 will change the paper color from purple to yellow (indicating EtCO2 values > 15 mm Hg).2,4 Without this color change, tube placement should be verified to rule out esophageal intubation. Unfortunately, qualitative capnography has false positives and negatives that limit its utility in the ED, and this method should be avoided if quantitative capnography is available.
With quantitative capnography, obtaining the typical box-waveform on the capnogram reflects endotracheal intubation. In comparison, a flat capnogram is more indicative of an esophageal intubation (Figure 3).10 While other things may cause this waveform, such as technical malfunction or complete airway obstruction distal to the tube, tube placement confirmation to rule out esophageal intubation would be the first step to troubleshooting this waveform. In addition, if the ETT is placed in the hypopharynx above the vocal cords, the waveform may initially appear appropriate but will likely become erratic appearing over time.10
Quantitative capnography does have some limitations. For example, a main-stem bronchus intubation would still likely demonstrate normal-appearing capnography, so secondary strategies and a confirmatory chest x-ray are still indicated. False-negative ETCO2 readings can occur in low CO2 elimination states, such as cardiac arrest, pulmonary embolus, or pulmonary edema, while false-positives can theoretically occur after ingestion of large amounts of carbonated liquids or contamination of the sensor with stomach contents or acidic drugs.10 However, many of these misleading results can be caught by simply checking for an appropriate waveform.
Cardiac Arrest
Capnography has numerous uses in the monitoring, management, and prognostication of intubated patients in cardiac arrest.1,3,4,10,14 Under normal conditions, EtCO2 is 35-40 mm Hg. While the body still makes CO2 during cardiac arrest, it will not reach the alveoli without circulating blood.10 Without CPR, CO2 accumulates peripherally and won’t reach the lungs, causing EtCO2 to approach zero. This means that EtCO2 correlates directly with cardiac output during CPR, as long as ventilation remains constant.
This means the effectiveness of cardiac chest compression can be assessed in intubated patients using EtCO2, with higher values during CPR correlated with increased return of spontaneous circulation (ROSC) and survival.14-18 Using EtCO2 monitoring during cardiac arrest may improve outcomes,19 and the American Heart Association (AHA) recommends monitoring capnography during cardiac arrest to assess compression efficacy.10,20 EtCO2 >20 mm Hg is considered optimal, while EtCO2 <10-15 mm Hg is considered suboptimal.4,10,16 In a recent meta-analysis, the average EtCO2 was 13.1 mm Hg in those who did not obtain ROSC, compared to 25.8 mm Hg in those who did.21 As such, goal EtCO2 for effective compressions may be even higher in future recommendations. If EtCO2 is low, either compression technique should be improved or a different operator should do compressions. Every 1 cm increase in depth will increase EtCO2 by approximately 1.4 mm Hg.16 Interestingly, compression rate is not a significant predictor of EtCO2 over the dynamic range of chest compression delivery.16
An abrupt increase in EtCO2 is an early indicator of ROSC.10,14-16,22,23 A return of a perfusing rhythm will increase cardiac output. This allows for accumulated peripheral CO2 to reach the lungs, subsequently causing a rapid rise in EtCO2.24 It is important to note that when it comes to evaluating for ROSC, the actual numbers are less important than the change from pre- to post-ROSC. Providers should look for a jump of at least 10 mm Hg on capnometry.4 Nevertheless, an abrupt rise in EtCO2 is a non-sensitive marker for ROSC (33%, 95% CI 22-47% in one multicenter cross-sectional study), meaning that the lack of an abrupt rise of EtCO2 may not necessarily mean a lack of ROSC.23
The EtCO2 level may help guide decision-making in assessing whether continued resuscitation in cardiac arrest is futile. Values <10 mm Hg after 20 minutes of active resuscitation have consistently demonstrated minimal chance of survival.17,25,26 In one study, an EtCO2 of <10 mm Hg at 20 minutes had a sensitivity, specificity, PPV, and NPV of 100% for death in PEA arrest.17 However, determination of the specific EtCO2 cutoff and the timing is still an area of research with a final consensus pending.17,18,25-30 One recent study suggested that even 3 min with EtCO2 <10 mm Hg could be an appropriate cutoff to cease resuscitation efforts.27
Unfortunately, there is a large amount of heterogeneity in the available literature using capnography to assess for ROSC and in guiding resuscitation efforts. EtCO2 should not be used as the only factor in the determination to cease resuscitation. In addition, the AHA recommends that EtCO2 for prognostication should be limited to intubated patients only.20
It is important to note that while cardiac output is the largest factor for EtCO2 in arrest, other physiologic and iatrogenic causes may affect EtCO2 during resuscitation. For example, there is considerable variation in EtCO2 with changes in ventilation rate.4 Measured CO2 may be significantly lower with manual instead of mechanical ventilation, likely due to over-ventilation that not only reduces alveolar CO2 but also causes excess intra-thoracic pressure, reducing venous return.21 For these reasons, use caution when using EtCO2 during manual ventilation of an intubated patient in cardiac arrest. In addition, administration of epinephrine may cause a small decrease in EtCO2, although the effect may vary for each individual.10,31 Sodium bicarbonate can also cause a transient increase in CO2 due to its conversion into CO2 and H2O.10
Procedural Sedation
Capnography is being used with increasing frequency to monitor patients during procedural sedation; it is now considered standard of care in many settings.32 Although rare, hypoventilation is a risk of procedural sedation.33 Typically, respiratory depression during procedural sedation is diagnosed with non-invasive pulse oximetry and visual inspection.34 However, capnography has been shown to identify respiratory depression, airway obstruction, apnea, and laryngospasm earlier than pulse oximetry, allowing the provider to intervene quicker.34,35 Unlike pulse oximetry, the capnogram also remains stable during patient motion and is reliable in low-perfusion states.36
There are two distinct types of hypoventilation detected by capnography. Bradypneic hypoventilation (type 1), which is characterized by a decreased respiratory rate, results in a decreased expiratory time and a subsequent rise in EtCO2.36 This is depicted on capnography by a high EtCO2 and longer waveform, and is commonly observed after oversedation with opioids (Figure 4).36 In contrast, hypopneic hypoventilation (type 2) occurs with low tidal volumes but a normal respiratory rate.36 Type 2 is graphically represented by a suddenly lower ETCO2 with otherwise normal waveform and occurs most commonly with sedative-hypnotic drugs (Figure 5).36 Seeing either type during procedural sedation should alert the clinician to assess for airway obstruction, consider supplemental oxygen, cease drug administration or reduce dosing, and consider reversal if appropriate.36
There is some debate as to the utility of capnography for procedural sedation. While it is clear that capnography decreases the incidence of hypoxia, some studies suggest that it may not reduce patient-centered outcomes such as adverse respiratory events, neurologic injury, aspiration, or death compared to standard monitoring.35,37,38 However, pulse oximetry alone can suffer response delay, while EtCO2 can rapidly detect hypoventilation.39
Potential Uses/Applications
Respiratory Distress
Capnography can provide dynamic monitoring in patients with acute respiratory distress. Measuring EtCO2 with each breath provides instantaneous feedback on the clinical status of the patient and has numerous specific uses.1,3,4
Determining the etiology of respiratory distress in either the obtunded patient or those with multiple comorbidities can be a challenge. Vital sign abnormalities and physical exam findings can overlap in numerous conditions, which may only further obscure the diagnosis. Since different etiologies for respiratory disease require different management modalities, anything that can help clue in to the specific cause can be beneficial. As discussed above, obstructive diseases such as COPD or asthma demonstrate a “shark-fin appearance” on capnogram due to both V/Q heterogeneity and a prolonged expiratory phase due to airway constriction, which will contrast to the typical box-waveform in other conditions (Figure 2).1,2,6 Some studies have been able differentiate COPD from congestive heart failure (CHF) by waveform analysis alone, though this was primarily done via computer algorithms.40 Seeing the shark-fin (or the lack thereof) can help guide management of respiratory distress in conjunction with the remainder of the initial assessment.
Monitoring capnography can help with management and disposition in those with COPD or asthma. During exacerbations, EtCO2 levels may initially drop as the patient hyperventilates to compensate.1 It is not until ventilation becomes less effective that EtCO2 levels begin to rise. This may occur before hypoxia sets in and can prompt the clinician to escalate ventilation strategies. In addition, the normalization of the “shark-fin” obstructive pattern towards the more typical box-form wave may indicate effective treatment, though more data is needed before it can be recommended.41 One of the advantages of this technique would be that it is independent of patient effort, unlike peak-flow monitoring.
EtCO2 can be beneficial even before patients get to the ED. In one study, prehospital patients presenting with asthma or COPD who were found to have EtCO2 of >50 mm Hg or <28 mm Hg, representing the upper and lower limits in the study, had greater rates of intubation, critical care admission, and mortality.42 The patients in this cohort with higher EtCO2 were likely tiring after prolonged hyperventilation and therefore would be more likely to need ventilatory support. Those on the lower end were likely hyperventilating and had not yet tired out. It is important to note that while arrival EtCO2 levels may aid in determining the more critically ill, post-treatment levels were not found to have a statistical difference in determining disposition in patients with asthma or COPD.43
Caution is advised when attempting to use EtCO2 to approximate an arterial blood gas CO2 (PaCO2). While EtCO2 can correlate with PaCO2 within 5 mm Hg in greater than 80% of patients with dyspnea,44 large discrepancies are common depending on the disease state.45 In general, the EtCO2 should always be lower than the PaCO2 due to the contribution to the ETCO2 from dead space, which has a low CO2 content due to lack of perfusion.
Sepsis
EtCO2 may help identify septic patients given its inverse relationship with lactate levels.46-49 In conditions of poor tissue perfusion, lactate builds up. This begins to make the blood acidotic in the form of newly acquired anions, with a resultant anion gap metabolic acidosis. The body then tries to acutely compensate for this by hyperventilating, resulting in the observed lowering of EtCO2. Since lactate is a predictor of mortality in sepsis,50 and monitoring lactate clearance to evaluate resuscitation efforts in sepsis is recommended,51 EtCO2 could play a similar role. One group in particular has demonstrated that, when used with SIRS criteria, abnormally low prehospital EtCO2 levels is predictive of sepsis and inhospital mortality, and is more predictive than SIRS criteria alone.48,50 That said, EtCO2 was not associated with lactate temporally at 3 and 6 hours,51 so it should not be used to guide resuscitation like a lactate clearance. It appears that EtCO2 may be helpful for triage in sepsis, but more study is needed to determine the exact role particularly given most of the available research involves multiple studies from one group.47,48,52
Diabetic Ketoacidosis
Initial bicarbonate levels and venous pH are associated with low EtCO2 readings in diabetic ketoacidosis (DKA).54,55 This could have many practical uses, in particular for patients presenting with hyperglycemia to rule out DKA. One study demonstrated that a blood glucose >250 mg/dL and capnography of >24.5 mm Hg had 90% sensitivity for excluding DKA.55 A value of 35 mm Hg or greater demonstrated 100% sensitivity for excluding DKA in patients with initial glucose >550 mg/dL,56 though this blood glucose is not practical, as this excludes many patients the EP would seek to rule out DKA (recall that blood glucose only has to be >250 mg/dL for the diagnosis). Smaller studies focused on the pediatric population found a 100% sensitivity marker for DKA varied from >30 to >36 mm Hg.57,58 Clearly a role exists, but no study has demonstrated sufficient sensitivity for ruling out DKA with EtCO2 and blood glucose alone within the framework of clinically relevant values.
Trauma
As described above, low EtCO2 is inversely correlated with lactate.46 Because of this, it could theoretically be a marker of hypoperfusion in trauma. Initial EtCO2 values <25 mm Hg have been associated with mortality and hemorrhage in intubated trauma patients,59 as well as mortality prior to discharge in nonintubated trauma patients.60 However, it did not demonstrate added clinical utility when combined with Glasgow Coma Scale (GCS) score, systolic blood pressure, and age in predicting severe injury.61
Pulmonary Embolism
A pulmonary embolism (PE) causes a blockage in blood flow to alveoli, which results in a decrease in CO2 transportation to the alveoli and thus lower EtCO2, while also widening the gradient between PaCO2 and EtCO2.37 Because of this, it has a theoretical role in the diagnosis of PE, though numerous studies have demonstrated that EtCO2 alone is not sensitive nor specific enough for this role.62-66 In a recent meta-analysis, a pretest probability of 10% could lead to a posttest probability of 3% using capnography.62 While further study is needed before recommendation, this indicates that capnography could obviate the need for imaging in low to intermediate risk patients either after a positive D-Dimer or instead of obtaining a D-dimer.62-64
Triage
Simply measuring an initial EtCO2 as a triage vital sign may have added benefit to the EP, and consideration could be made for making this a policy in your ED. One study demonstrated that abnormal initial EtCO2 (outside of 35-45 mm Hg) was predictive of admisison (RR 2.5, 95% CI 1.5-4.0).67 An abnormal EtCO2 (outside of 31-41 mm Hg for this study) was 93% sensitive (95% CI 79-98%), with expectedly low specificity of 44% (95% CI 41-48%) for mortality prior to discharge.47 This potential vital sign may be treated similarly to tachycardia; while an abnormal heart rate should increase a clinician’s concern for a pathological condition, it needs to be taken in context of the situation to accurately interpret it.
Summary
Capnography has numerous uses in the ED in both intubated and spontaneously breathing patients. Quantitative capnography is the standard of care for confirming endotracheal intubation. It is recommended as an aide in maximizing chest compressions during cardiac arrest and can assist in prognostication. It rapidly identifies hypoventilation during procedural sedation. It also has many more potential applications that continue to be explored in areas such as respiratory distress, sepsis, trauma, DKA, and PE. Ultimately, capnography should always be used in association with the remainder of the clinical assessment.
- Manifold CA, Davids B, Villers LC, Wampler DA. Capnography for the nonintubated patient in the emergency setting. J Emerg Med. 2013;45(4):626-632.
- Ward K, Yealy DM. End-tidal carbon dioxide monitoring in emergency medicine, part 1: basic principles. Acad Emerg Med. 1998;5(6):628-636.
- Krauss B, Falk JL. Carbon dioxide monitoring (capnography). UpToDate. Waltham MA: UpToDate Inc. www.uptodate.com.
- Long B, Koyfman A, Michael AV. Capnography in the emergency department: a review of uses, waveforms, and limitations. J Emerg Med. 2017;(53)6:829-842.
- Shankar Kodali B. Capnography: A Comprehensive Educational Website. Boston, MA. www.capnography.com.
- Kodali B. Capnography outside the operating room. Anesthesiology. 2013;118:192-201.
- Bhavani, S. Defining segments and phases of a time capnogram. Anesth Analg. 2000;91(4):973-977.
- Petersson J, Glenny R. Gas exchange and ventilation-perfusion relationships in the lung. Eur Resp J. 2014;44(4):1023-1041.
- Nassar B, Schmidt GA. Capnography during critical illness. Chest. 2016;149(2):576-585.
- Neumar RW, Otto CW, Link MS, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 suppl 3):S729-S767.
- Burns SM, Carpenter R, Blevins C, Bragg S, Marshall M, Browne L, et al. Detection of inadvertent airway intubation during gastric tube insertion: capnography versus a colorimetric carbon dioxide detector. Am J Crit Care. 2006:15(2):188-195.
- Goldberg JS, Rawle PR, Zehnder JL, Sladen RN. Colorimetric end-tidal carbon dioxide monitoring for tracheal intubation. Anesthesia and analgesia. 1990:70(2):191-194.
- O'Flaherty D, Adams AP. The end-tidal carbon dioxide detector: assessment of a new method to distinguish oesophageal from tracheal intubation. Anaesthesia. 1990:45(8):653-655.
- Garnett AR, Ornato JP, Gonzalez ER, Johnson EB. End-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. JAMA. 1987;257:512-515.
- Falk JL, Rackow EC, Weil MH. End-tidal carbon dioxide concentration during cardiopulmonary resuscitation. N Engl J Med. 1988;318(10):607-611.
- Sheak KR, Wiebe DJ, Leary M, Babaeizadeh S, Yuen TC, Zive D, et al. Quantitative relationship between end-tidal carbon dioxide and CPR quality during both in-hospital and out-of-hospital cardiac arrest. Resuscitation. 2015;89:149-154.
- Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med. 1997;337(5):301-306.
- Touma O, Davies M. The prognostic value of end tidal carbon dioxide during cardiac arrest: a systematic review. Resuscitation. 2013;84(11):1470-1479.
- Chen JJ, Lee YK, Hou SW, et al. End-tidal carbon dioxide monitoring may be associated with a higher possibility of return of spontaneous circulation during out-of-hospital cardiac arrest: a population-based study. Scan J Trauma Resusc Emerg Med. 2015;23:104.
- Neumar RW, Shuster M, Callaway CW et al. Part 7: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(suppl 2):S315-S367.
- Hartmann SW, Farris RW, Di Gennaro JL, Roberts JS. Systematic review and meta-analysis of end-tidal carbon dioxide values associated with return of spontaneous circulation during cardiopulmonary resuscitation. J Intensive Care Med. 2015;(30):426-435.
- Eckstein, M, Hatch, L, Malleck, J et al. EtCO2 as a predictor of survival in out-of hospital cardiac arrest. Prehosp Disaster Med. 2016;104:53-58.
- Lui CT, Poon KM, Tsui KL. Abrupt rise of end tidal carbon dioxide was a specific but non-sensitive marker of return of spontaneous circulation with out-of-hospital cardiac arrest. Resuscitation. 2016;104:53-58.
- Pokorna M, Necas E, Kratochvil J et al. A sudden increase in partial pressure end-tidal carbon dioxide at the moment of return of spontaneous circulation. J Emerg Med. 2010;38:614-621.
- Sanders A, Kern K, Otto C, et al. End-tidal carbon dixoide monitoring during cardiopulmonary resuscitation: a prognostic indicator for survival. JAMA. 1989;262:1347-1351.
- Wayne M, Levine R, And Miller C. Use of end-tidal carbon dioxide to predict outcome in prehospital cardiac arrest. Ann Emerg Med. 1995;25(6):762-767.
- Poon KM, Lui CT, Tsui KL. Prognostication of out-of-hopsital cardiac arrest patients by 3-min end-tidal capnometry level in emergency department. Resuscitation. 2016;102:80-84.
- Einav S, Bromiker R, Weiniger C, Matot I. Mathematical modeling for prediction of survival from resuscitation based on computerized continuous capnography: proof of concept. Acad Emerg Med. 2011;18:468-475.
- Pearce A, Davis D, Minokadeh A, Sell R. Initial end-tidal carbon dioxide as a prognostic indicator for inpatient PEA arrest. Resuscitation. 2015;92:77-81.
- Akinci, E, Ramadan H, Yuzbasioglu Y, Coksun F. Comparison of end-tidal carbon dioxide levels with cardiopulmonary resuscitation success presented to emergency department with cardiopulmonary arrest. Pak J Med Sci. 2014;30(1):16-21.
- Callaham M, Barton C, Matthay M. Effect of epinephrine on the ability of end-tidal carbon dioxide readings to predict initial resuscitation from cardiac arrest. Crit Care Med. 1992; 20:337-343.
- Wall BF, Magee K, Campbell SG, Zed PJ. Capnography versus standard monitoring for emergency department procedural sedation and analgesia. Cochrane Database of Systematic Reviews. 2017(3).
- Langhan ML, Shabanova V, Li FY, Bernstein SL, Shapiro ED. A randomized controlled trial of capnography during sedation in a pediatric emergency setting. Am J Emerg Med. 2015;33(1):25-30.
- Campbell SG, Magee KD, Zed PJ, Froese P, Etsell G, LaPierre A et al. End-tidal capnometry during emergency department procedural sedation and analgesia: a randomized, controlled study. World J Emerg Med. 2016;7(1):13.
- Waugh JB, Epps CA, Khodneva YA. Capnography enhances surveillance of respiratory events during procedural sedation: a meta-analysis. J Clin Anesth. 2011;23(3):189-196.
- Krauss B, Hess DR. Capnography for procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2007;50(2):172-181.
- Deitch K, Miner J, Chudnofsky CR, Dominici P, Latta D. Does end tidal CO2 monitoring during emergency department procedural sedation and analgesia with propofol decrease the incidence of hypoxic events? A randomized, controlled trial. Ann Emerg Med. 2010;55(3):258-264.
- Godwin SA, Caro DA, Wolf SJ, Jagoda AS, Charles R, Marett BE, Moore J. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2005;45(2):177-196.
- Hamber EA, Bailey PI, James SW et al. Delays in the detection of hypoxemia due to site of pulse oximetry pulse placement. J Clin Anesth. 1999;11:113-118.
- Mieloszyk RJ, Vergehese GC, Deitch K, et al. Automated quantitative analysis of capnogram shape for COPD-normal and COPD-CHF classification. IEEE Trans Biomed Eng. 2014;61:2882-2890.
- Howe TA, Jaalam K, R. Ahmad, Sheng CK, Ab Rahman NHN. The use of end-tidal capnography to monitor non-intubated patients presenting with acute exacerbation of asthma in the emergency department. J Emerg Med. 2011:41:581-589.
- Nagurka R, Bechmann S, Gluckman W et al. Utility of initial prehospital end-tidal carbon dioxide measurements to predict poor outcomes in adult asthmatic patients. Prehospital Emerg Care. 2014;18:180-184.
- Doğan NÖ, Şener A, Günaydın GP, İçme F, Çelik GK, Kavaklı HŞ, Temrel TA. The accuracy of mainstream end-tidal carbon dioxide levels to predict the severity of chronic obstructive pulmonary disease exacerbations presented to the ED. Am J Emerg Med. 2014;32(5):408-411.
- Cinar O, Acar YA, Arziman I, et al. Can mainstream end-tidal carbon dioxide measurement accurately predict the arterial carbon dioxide levels of patients with acute dyspnea in ED. Am J Emerg Med. 2012;30:358-361.
- Nassar BS, Schmidt GA. Capnography during critical illness. Chest. 2016:149(2):576-585.
- Caputo ND, Fraser RM, Paliga A et al. Nasal cannula end-tidal CO2 correlates with serum lactate levels and odds of operative intervention in penetrating trauma patients: a prospective cohort study. J Trauma Acute Care Surg. 2012;73:1202-1207.
- Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. 2014;32(2):160-165.
- Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. 2013;31(1):64-71.
- McGillicuddy DC, Tang A, Cataldo L, et al. Evaluation of end-tidal carbon dioxide role in predicting elevated SOFA and lactic acidosis. Intern Emerg Med. 2009;4:41-44.
- Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005;45:524-528.
- Levy, MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med. 2018;46:997-1000.
- Hunter CL, Silvestri S, Ralls G et al. A prehospital screening tool utilizing end-tidal carbon dioxide predicts sepsis and severe sepsis. Am J Emerg Med. 2016;34:813-819.
- Guirgis FW, Williams DJ, Kalynych CJ, Hardy ME, Jones AE, Dodani S, Wears RL. End-tidal carbon dioxide as a goal of early sepsis therapy. Am J Emerg Med. 2014;32(11):1351-1356.
- Kartal M, Eray O, Rinnert S, Gosku E, Bektas F, Eken C. ETCO2: a predictive tool for excluding metabolic disturbances in nonintubated patients. Am J Emerg Med. 2011;29: 65-69.
- Solmeinpur H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for diagnosis in patients with suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. 2013;14:590-594.
- Bou Chebl R, Madden B, Belsky J, Harmouche E, Yessayan L. Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. BMC Emerg Med. 2016;16:7.
- Fearon DM, Steele DW. End-tidal carbon dioxide predicts the presence and severity of acidosis in children with diabetes. Acad Emerg Med. 2002;9:1373-1378.
- Gilhotra Y, Porter P. Predicting diabetic ketoacidosis in children by measuring end-tidal CO2 via non-invasive nasal capnography. J Paediatr Child Health. 2007;43:677-680.
- Dunham CM, Chirichella TJ, Gruber BS, et al. In emergently ventilated trauma patients, low end-tidal CO2 and low cardiac output are associated and correlate with hemodynamic instability, hemorrhage, abnormal pupils, and death. BMC Anesthesiol. 2013;13-20.
- Deakin CD, Sado DM, Coats TJ, Davies G. Prehospital end-tidal carbon dioxide concentration and outcome in major trauma. J Trauma.2004;57:65-68.
- Williams DJ, Guirgis FW, Morrissey TK, Wilkerson J, Wears RL, Kalynych C, Kerwin AJ, Godwin SA. End-tidal carbon dioxide and occult injury in trauma patients: ETCO2 does not rule out severe injury. Am J Emerg Med. 2016;34(11):2146-2149.
- Manara A, D’hoore W, Thys F. Capnography as a diagnostic tool for pulmonary embolism: a meta-analysis. Ann Emerg Med. 2013;52:584-591.
- Yoon YH, Lee SW, Jung DM et al. The additional use of end-tidal alveolar dead space fraction following D-dimer test to improve diagnostic accuracy for pulmonary embolism in the emergency department. Emerg Med J. 2010;27:663-667.
- Hemnes AR, Newman AL, Rosenbaum B, et al. Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism. Eur Resp J. 2010;35:735-741.
- Rias I Jacob B. Pulmonary embolism in Bradford, UK: role of end-tidal CO2 as a screening tool. Clin Med (Lond). 2014;14:128-133.
- Yuksel M, Pekdemir M, Yilmaz S, et al. Diagnostic accuracy of noninvasive end-tidal carbon dioxide measurement in emergency department patients with suspected pulmonary embolism. Turk J Med Sci. 2016;46:84–90.
- Williams D, Morrissey T, Caro D, Wears R, Kalynyc C. Side-stream qunatitative end-tidal carbon dioxide measurement as a triage tool in emergency medicine. Ann Emerg Med. 2011;58:S212-S213.
- Manifold CA, Davids B, Villers LC, Wampler DA. Capnography for the nonintubated patient in the emergency setting. J Emerg Med. 2013;45(4):626-632.
- Ward K, Yealy DM. End-tidal carbon dioxide monitoring in emergency medicine, part 1: basic principles. Acad Emerg Med. 1998;5(6):628-636.
- Krauss B, Falk JL. Carbon dioxide monitoring (capnography). UpToDate. Waltham MA: UpToDate Inc. www.uptodate.com.
- Long B, Koyfman A, Michael AV. Capnography in the emergency department: a review of uses, waveforms, and limitations. J Emerg Med. 2017;(53)6:829-842.
- Shankar Kodali B. Capnography: A Comprehensive Educational Website. Boston, MA. www.capnography.com.
- Kodali B. Capnography outside the operating room. Anesthesiology. 2013;118:192-201.
- Bhavani, S. Defining segments and phases of a time capnogram. Anesth Analg. 2000;91(4):973-977.
- Petersson J, Glenny R. Gas exchange and ventilation-perfusion relationships in the lung. Eur Resp J. 2014;44(4):1023-1041.
- Nassar B, Schmidt GA. Capnography during critical illness. Chest. 2016;149(2):576-585.
- Neumar RW, Otto CW, Link MS, et al. Part 8: Adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 suppl 3):S729-S767.
- Burns SM, Carpenter R, Blevins C, Bragg S, Marshall M, Browne L, et al. Detection of inadvertent airway intubation during gastric tube insertion: capnography versus a colorimetric carbon dioxide detector. Am J Crit Care. 2006:15(2):188-195.
- Goldberg JS, Rawle PR, Zehnder JL, Sladen RN. Colorimetric end-tidal carbon dioxide monitoring for tracheal intubation. Anesthesia and analgesia. 1990:70(2):191-194.
- O'Flaherty D, Adams AP. The end-tidal carbon dioxide detector: assessment of a new method to distinguish oesophageal from tracheal intubation. Anaesthesia. 1990:45(8):653-655.
- Garnett AR, Ornato JP, Gonzalez ER, Johnson EB. End-tidal carbon dioxide monitoring during cardiopulmonary resuscitation. JAMA. 1987;257:512-515.
- Falk JL, Rackow EC, Weil MH. End-tidal carbon dioxide concentration during cardiopulmonary resuscitation. N Engl J Med. 1988;318(10):607-611.
- Sheak KR, Wiebe DJ, Leary M, Babaeizadeh S, Yuen TC, Zive D, et al. Quantitative relationship between end-tidal carbon dioxide and CPR quality during both in-hospital and out-of-hospital cardiac arrest. Resuscitation. 2015;89:149-154.
- Levine RL, Wayne MA, Miller CC. End-tidal carbon dioxide and outcome of out-of-hospital cardiac arrest. N Engl J Med. 1997;337(5):301-306.
- Touma O, Davies M. The prognostic value of end tidal carbon dioxide during cardiac arrest: a systematic review. Resuscitation. 2013;84(11):1470-1479.
- Chen JJ, Lee YK, Hou SW, et al. End-tidal carbon dioxide monitoring may be associated with a higher possibility of return of spontaneous circulation during out-of-hospital cardiac arrest: a population-based study. Scan J Trauma Resusc Emerg Med. 2015;23:104.
- Neumar RW, Shuster M, Callaway CW et al. Part 7: Executive Summary: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(suppl 2):S315-S367.
- Hartmann SW, Farris RW, Di Gennaro JL, Roberts JS. Systematic review and meta-analysis of end-tidal carbon dioxide values associated with return of spontaneous circulation during cardiopulmonary resuscitation. J Intensive Care Med. 2015;(30):426-435.
- Eckstein, M, Hatch, L, Malleck, J et al. EtCO2 as a predictor of survival in out-of hospital cardiac arrest. Prehosp Disaster Med. 2016;104:53-58.
- Lui CT, Poon KM, Tsui KL. Abrupt rise of end tidal carbon dioxide was a specific but non-sensitive marker of return of spontaneous circulation with out-of-hospital cardiac arrest. Resuscitation. 2016;104:53-58.
- Pokorna M, Necas E, Kratochvil J et al. A sudden increase in partial pressure end-tidal carbon dioxide at the moment of return of spontaneous circulation. J Emerg Med. 2010;38:614-621.
- Sanders A, Kern K, Otto C, et al. End-tidal carbon dixoide monitoring during cardiopulmonary resuscitation: a prognostic indicator for survival. JAMA. 1989;262:1347-1351.
- Wayne M, Levine R, And Miller C. Use of end-tidal carbon dioxide to predict outcome in prehospital cardiac arrest. Ann Emerg Med. 1995;25(6):762-767.
- Poon KM, Lui CT, Tsui KL. Prognostication of out-of-hopsital cardiac arrest patients by 3-min end-tidal capnometry level in emergency department. Resuscitation. 2016;102:80-84.
- Einav S, Bromiker R, Weiniger C, Matot I. Mathematical modeling for prediction of survival from resuscitation based on computerized continuous capnography: proof of concept. Acad Emerg Med. 2011;18:468-475.
- Pearce A, Davis D, Minokadeh A, Sell R. Initial end-tidal carbon dioxide as a prognostic indicator for inpatient PEA arrest. Resuscitation. 2015;92:77-81.
- Akinci, E, Ramadan H, Yuzbasioglu Y, Coksun F. Comparison of end-tidal carbon dioxide levels with cardiopulmonary resuscitation success presented to emergency department with cardiopulmonary arrest. Pak J Med Sci. 2014;30(1):16-21.
- Callaham M, Barton C, Matthay M. Effect of epinephrine on the ability of end-tidal carbon dioxide readings to predict initial resuscitation from cardiac arrest. Crit Care Med. 1992; 20:337-343.
- Wall BF, Magee K, Campbell SG, Zed PJ. Capnography versus standard monitoring for emergency department procedural sedation and analgesia. Cochrane Database of Systematic Reviews. 2017(3).
- Langhan ML, Shabanova V, Li FY, Bernstein SL, Shapiro ED. A randomized controlled trial of capnography during sedation in a pediatric emergency setting. Am J Emerg Med. 2015;33(1):25-30.
- Campbell SG, Magee KD, Zed PJ, Froese P, Etsell G, LaPierre A et al. End-tidal capnometry during emergency department procedural sedation and analgesia: a randomized, controlled study. World J Emerg Med. 2016;7(1):13.
- Waugh JB, Epps CA, Khodneva YA. Capnography enhances surveillance of respiratory events during procedural sedation: a meta-analysis. J Clin Anesth. 2011;23(3):189-196.
- Krauss B, Hess DR. Capnography for procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2007;50(2):172-181.
- Deitch K, Miner J, Chudnofsky CR, Dominici P, Latta D. Does end tidal CO2 monitoring during emergency department procedural sedation and analgesia with propofol decrease the incidence of hypoxic events? A randomized, controlled trial. Ann Emerg Med. 2010;55(3):258-264.
- Godwin SA, Caro DA, Wolf SJ, Jagoda AS, Charles R, Marett BE, Moore J. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2005;45(2):177-196.
- Hamber EA, Bailey PI, James SW et al. Delays in the detection of hypoxemia due to site of pulse oximetry pulse placement. J Clin Anesth. 1999;11:113-118.
- Mieloszyk RJ, Vergehese GC, Deitch K, et al. Automated quantitative analysis of capnogram shape for COPD-normal and COPD-CHF classification. IEEE Trans Biomed Eng. 2014;61:2882-2890.
- Howe TA, Jaalam K, R. Ahmad, Sheng CK, Ab Rahman NHN. The use of end-tidal capnography to monitor non-intubated patients presenting with acute exacerbation of asthma in the emergency department. J Emerg Med. 2011:41:581-589.
- Nagurka R, Bechmann S, Gluckman W et al. Utility of initial prehospital end-tidal carbon dioxide measurements to predict poor outcomes in adult asthmatic patients. Prehospital Emerg Care. 2014;18:180-184.
- Doğan NÖ, Şener A, Günaydın GP, İçme F, Çelik GK, Kavaklı HŞ, Temrel TA. The accuracy of mainstream end-tidal carbon dioxide levels to predict the severity of chronic obstructive pulmonary disease exacerbations presented to the ED. Am J Emerg Med. 2014;32(5):408-411.
- Cinar O, Acar YA, Arziman I, et al. Can mainstream end-tidal carbon dioxide measurement accurately predict the arterial carbon dioxide levels of patients with acute dyspnea in ED. Am J Emerg Med. 2012;30:358-361.
- Nassar BS, Schmidt GA. Capnography during critical illness. Chest. 2016:149(2):576-585.
- Caputo ND, Fraser RM, Paliga A et al. Nasal cannula end-tidal CO2 correlates with serum lactate levels and odds of operative intervention in penetrating trauma patients: a prospective cohort study. J Trauma Acute Care Surg. 2012;73:1202-1207.
- Hunter CL, Silvestri S, Ralls G, Bright S, Papa L. The sixth vital sign: prehospital end-tidal carbon dioxide predicts in-hospital mortality and metabolic disturbances. Am J Emerg Med. 2014;32(2):160-165.
- Hunter CL, Silvestri S, Dean M, Falk JL, Papa L. End-tidal carbon dioxide is associated with mortality and lactate in patients with suspected sepsis. Am J Emerg Med. 2013;31(1):64-71.
- McGillicuddy DC, Tang A, Cataldo L, et al. Evaluation of end-tidal carbon dioxide role in predicting elevated SOFA and lactic acidosis. Intern Emerg Med. 2009;4:41-44.
- Shapiro NI, Howell MD, Talmor D, Nathanson LA, Lisbon A, Wolfe RE, et al. Serum lactate as a predictor of mortality in emergency department patients with infection. Ann Emerg Med. 2005;45:524-528.
- Levy, MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med. 2018;46:997-1000.
- Hunter CL, Silvestri S, Ralls G et al. A prehospital screening tool utilizing end-tidal carbon dioxide predicts sepsis and severe sepsis. Am J Emerg Med. 2016;34:813-819.
- Guirgis FW, Williams DJ, Kalynych CJ, Hardy ME, Jones AE, Dodani S, Wears RL. End-tidal carbon dioxide as a goal of early sepsis therapy. Am J Emerg Med. 2014;32(11):1351-1356.
- Kartal M, Eray O, Rinnert S, Gosku E, Bektas F, Eken C. ETCO2: a predictive tool for excluding metabolic disturbances in nonintubated patients. Am J Emerg Med. 2011;29: 65-69.
- Solmeinpur H, Taghizadieh A, Niafar M, Rahmani F, Golzari SE, Esfanjani RM. Predictive value of capnography for diagnosis in patients with suspected diabetic ketoacidosis in the emergency department. West J Emerg Med. 2013;14:590-594.
- Bou Chebl R, Madden B, Belsky J, Harmouche E, Yessayan L. Diagnostic value of end tidal capnography in patients with hyperglycemia in the emergency department. BMC Emerg Med. 2016;16:7.
- Fearon DM, Steele DW. End-tidal carbon dioxide predicts the presence and severity of acidosis in children with diabetes. Acad Emerg Med. 2002;9:1373-1378.
- Gilhotra Y, Porter P. Predicting diabetic ketoacidosis in children by measuring end-tidal CO2 via non-invasive nasal capnography. J Paediatr Child Health. 2007;43:677-680.
- Dunham CM, Chirichella TJ, Gruber BS, et al. In emergently ventilated trauma patients, low end-tidal CO2 and low cardiac output are associated and correlate with hemodynamic instability, hemorrhage, abnormal pupils, and death. BMC Anesthesiol. 2013;13-20.
- Deakin CD, Sado DM, Coats TJ, Davies G. Prehospital end-tidal carbon dioxide concentration and outcome in major trauma. J Trauma.2004;57:65-68.
- Williams DJ, Guirgis FW, Morrissey TK, Wilkerson J, Wears RL, Kalynych C, Kerwin AJ, Godwin SA. End-tidal carbon dioxide and occult injury in trauma patients: ETCO2 does not rule out severe injury. Am J Emerg Med. 2016;34(11):2146-2149.
- Manara A, D’hoore W, Thys F. Capnography as a diagnostic tool for pulmonary embolism: a meta-analysis. Ann Emerg Med. 2013;52:584-591.
- Yoon YH, Lee SW, Jung DM et al. The additional use of end-tidal alveolar dead space fraction following D-dimer test to improve diagnostic accuracy for pulmonary embolism in the emergency department. Emerg Med J. 2010;27:663-667.
- Hemnes AR, Newman AL, Rosenbaum B, et al. Bedside end-tidal CO2 tension as a screening tool to exclude pulmonary embolism. Eur Resp J. 2010;35:735-741.
- Rias I Jacob B. Pulmonary embolism in Bradford, UK: role of end-tidal CO2 as a screening tool. Clin Med (Lond). 2014;14:128-133.
- Yuksel M, Pekdemir M, Yilmaz S, et al. Diagnostic accuracy of noninvasive end-tidal carbon dioxide measurement in emergency department patients with suspected pulmonary embolism. Turk J Med Sci. 2016;46:84–90.
- Williams D, Morrissey T, Caro D, Wears R, Kalynyc C. Side-stream qunatitative end-tidal carbon dioxide measurement as a triage tool in emergency medicine. Ann Emerg Med. 2011;58:S212-S213.
Treprostinil improves function for complex PAH patients
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
Treatment with , a study based on data from 105 adults has shown.
Data on the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) with treprostinil are limited, although alternatives to surgery are needed for many patients with the condition, wrote Roela Sadushi-Koliçi, MD, of the Medical University of Vienna, and her colleagues.
The researchers conducted a phase 3 randomized, controlled trial of the safety and efficacy of subcutaneous treprostinil for nonoperable CTEPH or persistent or recurrent pulmonary hypertension after pulmonary endarterectomy; the findings were published online in the Lancet Respiratory Medicine. The patients received continuous subcutaneous treprostinil at either 30 ng/kg per min (high dose) or 3 ng/kg per min (low dose) and all patients were assessed at weeks 6, 12, 18, and 24.
Overall, 6-minute walk distance, hemodynamics, and functional status significantly improved in the high-dose patients, compared with the low-dose patients.
The primary outcome of 6-minute walk distance increased by 44.98 m from baseline in the high-dose group, compared with an increase of 4.29 m from baseline in the low-dose group.
In addition, “changes in pulmonary vascular resistance, one of the most important prognostic indicators of CTEPH, were significant in favour of high-dose subcutaneous treprostinil, as were improvements of WHO functional class and N-terminal probrain natriuretic peptide,” the researchers noted.
Rates of serious adverse events were similar between the groups; a total of 12 serious adverse events were reported in 10 of 52 patients in the low-dose group (19%) and 16 serious adverse events were reported in 9 of 53 patients in the high-dose group (17%). In both groups, the most common treatment-related adverse events were infusion site pain and other infusion site reactions.
The findings were limited by the small sample size and the possibility that the 6-minute walk test might not translate to long-term outcomes for PAH and CTEPH, the researchers wrote. However, the data support the safety and efficacy of subcutaneous treprostinil for CTEPH patients who do not tolerate riociguat, the other approved option for nonoperable CTEPH, or those who need combination therapy, they said.
The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
SOURCE: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
FROM THE LANCET RESPIRATORY MEDICINE
Key clinical point: Treprostinil is a safe and effective nonsurgical treatment option for severe CTEPH patients.
Major finding: After 24 weeks, 6-minute walk distance improved by 44.98 m from baseline in the high-dose group compared with an increase of 4.29 m from baseline in the low-dose group.
Study details: The data come from a randomized trial of 105 adults with confirmed CTEPH.
Disclosures: The study was supported in part by SciPharm Sàrl and United Therapeutics, which provided the medication for part of the study. Dr. Sadushi-Koliçi disclosed relationships with Actelion, AOP Orphan Pharmaceuticals, Bayer Schering Pharma, GlaxoSmithKline, and SciPharm Sàrl, among others.
Source: Sadushi-Koliçi R et al. Lancet Respir Med. 2018 Nov 23. doi: 10.1016/S2213-2600(18)30367-9.
New CHEST expert panel advice on cough diagnosis
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
The CHEST Expert Cough Panel has released two new in adults and children.
Upper and lower respiratory tract infections are a common reason for primary care visits. A cough caused by influenza or pneumonia represents an opportunity to intervene for a significant benefit. The recommendations were published in CHEST®. The panel drafted recommendations based on available evidence and graded them using the CHEST grading system. The grading is based on the strength of the recommendation (either strong or weak) and a rating of the overall quality of the body of evidence. Where available evidence was weak, but guidance was still warranted, a weak suggestion was developed and graded 2C. Recommendations based on consensus in cases of insufficient clinical evidence are labeled “ungraded consensus-based statement.”
Suspected pneumonia or influenza
In adult outpatients with acute cough, the clinical signs of pneumonia include cough, dyspnea, pleural pain, sweating/fevers/shivers, aches and pains, temperature greater than or equal to 38°C, tachypnea, and new and localizing chest examination signs. When pneumonia is suspected to cause acute cough, C-reactive protein (CRP) should be measured. A CRP value higher than 30 mg/L bolsters the case for pneumonia, whereas a CRP value of lower than 10 mg/L, or between 10 mg/L and 50 mg/L in the absence of dyspnea and daily fever, makes pneumonia less likely.
The guidelines recommend against routine measurement of procalcitonin for outpatient adults suspected to have pneumonia. For adults with acute cough and abnormal vital signs believed to be secondary to pneumonia, the guidelines call for a chest x-ray.
Routine microbiological testing need not be performed in suspected pneumonia, but it should be considered if the results could guide or lead to a change in therapy.
When pneumonia is suspected but imaging is unavailable, empiric antibiotics should be used in concordance with local and national guidelines. If imaging turns up negative, antibiotics should not be used. However, if there is no clinical or radiographic evidence of pneumonia, antibiotics should not be used routinely.
Finally, adult patients with acute cough and suspected influenza should begin antiviral treatment within 48 hours of the start of symptoms.
Pertussis
Pertussis has significant morbidity and mortality, with infants being particularly vulnerable, and it is highly contagious. Although antibiotics will not affect the course of the disease, they should be administered as quickly as possible in order to prevent further spread. This puts pressure on the clinician to make a treatment decision before further testing is available.
A prespecified meta-analysis found high sensitivity and low specificity for paroxysmal cough (sensitivity, 93.2%; specificity, 20.6%) and absence of fever (sensitivity, 81.8%; specificity, 18.8%). The study found low sensitivity and high specificity for inspiratory whoop (sensitivity, 29.8%; specificity, 79.5%) and posttussive vomiting (sensitivity, 32.5%; specificity, 77.7%). In children, the review found that posttussive vomiting was moderately sensitive (60.0%) and specific (66.0%).
In adult patients with acute cough (less than 3 weeks’ duration) or subacute cough (3-8 weeks), the new guidelines recommend that physicians consider four key characteristics: the presence of recurrent, prolonged coughing episodes with an inability to breathe during the spell (paroxysmal); posttussive vomiting; inspiratory whooping; and presence of fever.
In acute or subacute cough, if the patient has a fever (body temperature greater than 98.6° F or 37.6° C) or does not have a paroxysmal cough, pertussis is unlikely. On the other hand, posttussive vomiting or an associated inspiratory whooping sound suggests pertussis.
Children with a cough lasting fewer than 4 weeks (acute) should be assessed for paroxysmal cough, posttussive vomiting, and inspiratory whooping. A cough associated with any of these characteristics may be caused by pertussis.
SOURCES: Moore A et al. CHEST. 2019 Jan;155:147-154; Hill A et al. CHEST. 2019 Jan;155:155-167.
FROM THE JOURNAL CHEST®
LAIV4 was less effective for children than IIV against influenza A/H1N1pdm09
The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.
Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.
The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.
Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.
With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.
“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.
Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.
The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.
SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.
There are many explanations for the decline in effectiveness of the live attenuated influenza vaccine (LAIV4), but the data are complicated by conflicting information from studies outside the United States indicating “reasonable protection” against influenza A/H1N1pdm09, A/H3N2, and influenza B, compared with the inactivated influenza virus (IIV), Pedro A. Piedra, MD, wrote in an accompanying editorial.
In 2016, the World Health Organization met to discuss LAIV effectiveness and highlighted factors such as methodological study differences, inadequate vaccine handling at distribution centers, intrinsic virological differences of the A/H1N1pdm09 virus, and increased preexisting population immunity in the United States since 2010 as potential explanations. During the transition from LAIV3 to LAIV4 for the 2013-2014 influenza season, viral interference may have also occurred when the influenza B strain was introduced into the vaccine, he added.
According to the CDC’s Advisory Committee on Immunization Practices (ACIP), viral growth properties of A/H1N1pdm09 has improved in LAIV4, and viral shedding also has improved for children between 2 years and 4 years of age. Although effectiveness numbers were not available for the ACIP recommendation, an interim analysis from Public Health England for the 2017-2018 influenza season found a vaccine effectiveness of 90.3% (95% confidence interval, 16.4%-98.9%).
“This early result is encouraging and supports the reintroduction of LAIV4 in the United States as an option for the control of seasonal influenza,” he said. “It also highlights the need for annual influenza vaccine effectiveness estimates and the importance of the U.S. Influenza Vaccine Effectiveness Network in providing updated information for ACIP recommendations.”
Dr. Piedra is from the departments of molecular virology and microbiology and pediatrics, Baylor College of Medicine, Houston. He reports being a consultant for AstraZeneca, Sanofi Pasteur, GlaxoSmithKline, and Merck Sharp and Dohme, and he has received travel support to present at an influenza seminar supported by Seqirus. His comments are from an editorial accompanying the article by Chung and colleagues ( Pediatrics. 2019. doi: 10.1542/peds.2018- 3290 ).
There are many explanations for the decline in effectiveness of the live attenuated influenza vaccine (LAIV4), but the data are complicated by conflicting information from studies outside the United States indicating “reasonable protection” against influenza A/H1N1pdm09, A/H3N2, and influenza B, compared with the inactivated influenza virus (IIV), Pedro A. Piedra, MD, wrote in an accompanying editorial.
In 2016, the World Health Organization met to discuss LAIV effectiveness and highlighted factors such as methodological study differences, inadequate vaccine handling at distribution centers, intrinsic virological differences of the A/H1N1pdm09 virus, and increased preexisting population immunity in the United States since 2010 as potential explanations. During the transition from LAIV3 to LAIV4 for the 2013-2014 influenza season, viral interference may have also occurred when the influenza B strain was introduced into the vaccine, he added.
According to the CDC’s Advisory Committee on Immunization Practices (ACIP), viral growth properties of A/H1N1pdm09 has improved in LAIV4, and viral shedding also has improved for children between 2 years and 4 years of age. Although effectiveness numbers were not available for the ACIP recommendation, an interim analysis from Public Health England for the 2017-2018 influenza season found a vaccine effectiveness of 90.3% (95% confidence interval, 16.4%-98.9%).
“This early result is encouraging and supports the reintroduction of LAIV4 in the United States as an option for the control of seasonal influenza,” he said. “It also highlights the need for annual influenza vaccine effectiveness estimates and the importance of the U.S. Influenza Vaccine Effectiveness Network in providing updated information for ACIP recommendations.”
Dr. Piedra is from the departments of molecular virology and microbiology and pediatrics, Baylor College of Medicine, Houston. He reports being a consultant for AstraZeneca, Sanofi Pasteur, GlaxoSmithKline, and Merck Sharp and Dohme, and he has received travel support to present at an influenza seminar supported by Seqirus. His comments are from an editorial accompanying the article by Chung and colleagues ( Pediatrics. 2019. doi: 10.1542/peds.2018- 3290 ).
There are many explanations for the decline in effectiveness of the live attenuated influenza vaccine (LAIV4), but the data are complicated by conflicting information from studies outside the United States indicating “reasonable protection” against influenza A/H1N1pdm09, A/H3N2, and influenza B, compared with the inactivated influenza virus (IIV), Pedro A. Piedra, MD, wrote in an accompanying editorial.
In 2016, the World Health Organization met to discuss LAIV effectiveness and highlighted factors such as methodological study differences, inadequate vaccine handling at distribution centers, intrinsic virological differences of the A/H1N1pdm09 virus, and increased preexisting population immunity in the United States since 2010 as potential explanations. During the transition from LAIV3 to LAIV4 for the 2013-2014 influenza season, viral interference may have also occurred when the influenza B strain was introduced into the vaccine, he added.
According to the CDC’s Advisory Committee on Immunization Practices (ACIP), viral growth properties of A/H1N1pdm09 has improved in LAIV4, and viral shedding also has improved for children between 2 years and 4 years of age. Although effectiveness numbers were not available for the ACIP recommendation, an interim analysis from Public Health England for the 2017-2018 influenza season found a vaccine effectiveness of 90.3% (95% confidence interval, 16.4%-98.9%).
“This early result is encouraging and supports the reintroduction of LAIV4 in the United States as an option for the control of seasonal influenza,” he said. “It also highlights the need for annual influenza vaccine effectiveness estimates and the importance of the U.S. Influenza Vaccine Effectiveness Network in providing updated information for ACIP recommendations.”
Dr. Piedra is from the departments of molecular virology and microbiology and pediatrics, Baylor College of Medicine, Houston. He reports being a consultant for AstraZeneca, Sanofi Pasteur, GlaxoSmithKline, and Merck Sharp and Dohme, and he has received travel support to present at an influenza seminar supported by Seqirus. His comments are from an editorial accompanying the article by Chung and colleagues ( Pediatrics. 2019. doi: 10.1542/peds.2018- 3290 ).
The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.
Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.
The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.
Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.
With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.
“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.
Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.
The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.
SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.
The live attenuated influenza vaccine was less effective against the influenza A/H1N1pdm09 virus in children and adolescents across multiple influenza seasons between 2013 and 2016, compared with the inactivated influenza vaccine, according to research published in the journal Pediatrics.
Jessie R. Chung, MPH, from the influenza division at the Centers for Disease Control and Prevention in Atlanta, and her colleagues performed an analysis of five different studies where vaccine effectiveness (VE) was examined for quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) in children and adolescents aged 2-17 years from 42 states.
The analysis included data from the U.S. Influenza Vaccine Effectiveness Network (6,793 patients), a study from the Louisiana State University Health Sciences Center (3,822 patients), the Influenza Clinical Investigation for Children (3,521 patients), Department of Defense Global, Laboratory-based, Influenza Surveillance Program (1,935 patients), and the Influenza Incidence Surveillance Project (1,102 patients) between the periods of 2013-2014 and 2015-2016. The researchers sourced current and previous season vaccination history from electronic medical records and immunization registries.
Of patients who were vaccinated across all seasons, there was 67% effectiveness against influenza A/H1N1pdm09 (95% confidence interval, 62%-72%) for those who received the IIV and 20% (95% CI, −6%-39%) for LAIV4. Among patients who received the LAIV4 vaccination, there was a significantly higher likelihood of developing influenza A/H1N1pdm09 (odds ratio, 2.66; 95% CI, 2.06-3.44) compared with patients who received the IIV vaccination.
With regard to other strains, there was similar effectiveness against influenza A/H3N2 and influenza B with LAIV4 and IIV vaccinations.
“In contrast to findings of reduced LAIV4 effectiveness against influenza A/H1N1pdm09 viruses, our results suggest a possible but nonsignificant benefit of LAIV4 over IIV against influenza B viruses, which has been described previously,” the investigators wrote.
Limitations of the study included having data only one season prior to enrollment and little available demographic information beyond age, gender, and geographic location.
The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.
SOURCE: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.
FROM PEDIATRICS
Key clinical point: The live attenuated influenza vaccine (LAIV4) was significantly less effective than was the inactivated influenza vaccine (IIV) for children against the influenza A/H1N1pdm09 virus across multiple flu seasons.
Major finding:
Study details: A combined analysis of five studies in the United States between the periods of 2013-2014 and 2015-2016 from the U.S. Influenza Vaccine Effectiveness Network.
Disclosures: The Influenza Clinical Investigation for Children was funded by MedImmune, a member of the AstraZeneca Group. Two of the researchers are employees of AstraZeneca. The other authors reported having no conflicts of interest. The U.S. Influenza Vaccine Effectiveness Network was supported by the CDC through cooperative agreements with the University of Michigan, Kaiser Permanente Washington Health Research Institute, Marshfield Clinic Research Institute, University of Pittsburgh, and Baylor Scott & White Health. At the University of Pittsburgh, the project also was supported by the National Institutes of Health.
Source: Chung JR et al. Pediatrics. 2018. doi: 10.1542/peds.2018-2094.