Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series
Background Mechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of C...
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| Veröffentlicht in: | Molecular Medicine 2020-09, Vol.26 (1), p.91-91, Article 91 |
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| description | Background Mechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system. Methods Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed. Results The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified. Conclusions Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered. |
| doi_str_mv | 10.1186/s10020-020-00215-w |
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DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system. Methods Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed. Results The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified. Conclusions Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.</description><identifier>ISSN: 1076-1551</identifier><identifier>EISSN: 1528-3658</identifier><identifier>DOI: 10.1186/s10020-020-00215-w</identifier><identifier>PMID: 32993479</identifier><language>eng</language><publisher>NEW YORK: Springer Nature</publisher><subject><![CDATA[Adult ; Aged ; Albuterol - administration & dosage ; Albuterol - therapeutic use ; Biochemistry & Molecular Biology ; Body mass index ; Bronchodilator Agents - administration & dosage ; Bronchodilator Agents - therapeutic use ; Cell Biology ; Coronavirus ; Coronavirus Infections - drug therapy ; Coronavirus Infections - therapy ; Coronaviruses ; COVID-19 ; Dehydrogenases ; Deoxyribonuclease I - administration & dosage ; Deoxyribonuclease I - therapeutic use ; Dornase alfa ; Extracorporeal membrane oxygenation ; Female ; Health aspects ; Hemoptysis ; Hispanic people ; Humans ; Hypertension ; Intensive care ; Intubation ; Intubation, Intratracheal ; Laboratories ; Life Sciences & Biomedicine ; Male ; Medical records ; Medical research ; Medicine, Research & Experimental ; Mortality ; Mucopurulent secretions ; Nebulizers and Vaporizers ; Neutrophil extracellular traps ; Neutrophils ; Pandemics ; Patients ; Pneumonia, Viral - drug therapy ; Pneumonia, Viral - therapy ; Recombinant Proteins - administration & dosage ; Recombinant Proteins - therapeutic use ; Research & Experimental Medicine ; Respiration, Artificial ; SARS-CoV-2 ; Science & Technology ; Severe acute respiratory syndrome coronavirus 2 ; Short Report ; Systemic diseases ; Thrombosis ; Ventilators]]></subject><ispartof>Molecular Medicine, 2020-09, Vol.26 (1), p.91-91, Article 91</ispartof><rights>COPYRIGHT 2020 Springer</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>31</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000576900900002</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c663t-bd12fccfd4433fb25068972ae5ceb4bc6ce5bcae075fed4fe7ba9870f9c258fb3</citedby><cites>FETCH-LOGICAL-c663t-bd12fccfd4433fb25068972ae5ceb4bc6ce5bcae075fed4fe7ba9870f9c258fb3</cites><orcidid>0000-0001-6766-4352 ; 0000-0001-9800-3709</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522910/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7522910/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2115,27929,27930,28253,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32993479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weber, Andrew G.</creatorcontrib><creatorcontrib>Chau, Alice S.</creatorcontrib><creatorcontrib>Egeblad, Mikala</creatorcontrib><creatorcontrib>Barnes, Betsy J.</creatorcontrib><creatorcontrib>Janowitz, Tobias</creatorcontrib><title>Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series</title><title>Molecular Medicine</title><addtitle>MOL MED</addtitle><addtitle>Mol Med</addtitle><description>Background Mechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system. Methods Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed. Results The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified. Conclusions Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.</description><subject>Adult</subject><subject>Aged</subject><subject>Albuterol - administration & dosage</subject><subject>Albuterol - therapeutic use</subject><subject>Biochemistry & Molecular Biology</subject><subject>Body mass index</subject><subject>Bronchodilator Agents - administration & dosage</subject><subject>Bronchodilator Agents - therapeutic use</subject><subject>Cell Biology</subject><subject>Coronavirus</subject><subject>Coronavirus Infections - drug therapy</subject><subject>Coronavirus Infections - therapy</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Dehydrogenases</subject><subject>Deoxyribonuclease I - administration & dosage</subject><subject>Deoxyribonuclease I - therapeutic use</subject><subject>Dornase alfa</subject><subject>Extracorporeal membrane oxygenation</subject><subject>Female</subject><subject>Health aspects</subject><subject>Hemoptysis</subject><subject>Hispanic people</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Intensive care</subject><subject>Intubation</subject><subject>Intubation, Intratracheal</subject><subject>Laboratories</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>Medical records</subject><subject>Medical research</subject><subject>Medicine, Research & Experimental</subject><subject>Mortality</subject><subject>Mucopurulent secretions</subject><subject>Nebulizers and Vaporizers</subject><subject>Neutrophil extracellular traps</subject><subject>Neutrophils</subject><subject>Pandemics</subject><subject>Patients</subject><subject>Pneumonia, Viral - drug therapy</subject><subject>Pneumonia, Viral - therapy</subject><subject>Recombinant Proteins - administration & dosage</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Research & Experimental Medicine</subject><subject>Respiration, Artificial</subject><subject>SARS-CoV-2</subject><subject>Science & Technology</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Short Report</subject><subject>Systemic diseases</subject><subject>Thrombosis</subject><subject>Ventilators</subject><issn>1076-1551</issn><issn>1528-3658</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>AOWDO</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNqNkk1v1DAQhiMEoqXwBzigSFyQUIrtxEnMAalavipV9AJcrbE9bl157RInXZUjv5zpbqkoJxRbdsbPvPJ43qp6ztkh52P_pnDGBGu2kwkum82Dap9LMTZtL8eHtGdD33Ap-V71pJSLLdTJx9VeK5Rqu0HtV7--oFli-ImuDqmJIWGNyeV5AnuOEGuXpwQFa4geakiONmaZccqxBrcOKRT6oeQ512u055CChRiv6ytMc4gw09Hq9Pvx-4ar-hLmQOHytoba3ogWnAKWp9UjD7Hgs9v1oPr28cPX1efm5PTT8eropLF9386NcVx4a73rurb1RkjWj2oQgNKi6YztLUpjAdkgPbrO42BAjQPzygo5etMeVMc7XZfhQl9OYQ3Ttc4Q9DaQpzMN0xxsRI1AL9g75QbnO1AehAWGHTLTMsM8J613O63LxazRWSprgnhP9P5JCuf6LF_pQQqhOCOBV7cCU_6xYJn1OhSLMULCvBQtum6gXrVKEvryH_QiL9SVSJTsetX2A73IQXW4o86ACgjJb3tIn8N1sDmhDxQ_6tthVJz3IyWIXYKdcikT-rvbc6Zv_KV3_tLbeWMdvaGkF3_XfZfyx1AEvN4BGzTZF0sNt3iHMcbk0CvGaJAk0eP_06swk4FyWuUlze1vfZnvrg</recordid><startdate>20200929</startdate><enddate>20200929</enddate><creator>Weber, Andrew G.</creator><creator>Chau, Alice S.</creator><creator>Egeblad, Mikala</creator><creator>Barnes, Betsy J.</creator><creator>Janowitz, Tobias</creator><general>Springer Nature</general><general>Springer</general><general>BioMed Central</general><general>BMC</general><scope>AOWDO</scope><scope>BLEPL</scope><scope>DTL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IAO</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0001-6766-4352</orcidid><orcidid>https://orcid.org/0000-0001-9800-3709</orcidid></search><sort><creationdate>20200929</creationdate><title>Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series</title><author>Weber, Andrew G. ; Chau, Alice S. ; Egeblad, Mikala ; Barnes, Betsy J. ; Janowitz, Tobias</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c663t-bd12fccfd4433fb25068972ae5ceb4bc6ce5bcae075fed4fe7ba9870f9c258fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Albuterol - administration & dosage</topic><topic>Albuterol - therapeutic use</topic><topic>Biochemistry & Molecular Biology</topic><topic>Body mass index</topic><topic>Bronchodilator Agents - administration & dosage</topic><topic>Bronchodilator Agents - therapeutic use</topic><topic>Cell Biology</topic><topic>Coronavirus</topic><topic>Coronavirus Infections - drug therapy</topic><topic>Coronavirus Infections - therapy</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>Dehydrogenases</topic><topic>Deoxyribonuclease I - administration & dosage</topic><topic>Deoxyribonuclease I - therapeutic use</topic><topic>Dornase alfa</topic><topic>Extracorporeal membrane oxygenation</topic><topic>Female</topic><topic>Health aspects</topic><topic>Hemoptysis</topic><topic>Hispanic people</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Intensive care</topic><topic>Intubation</topic><topic>Intubation, Intratracheal</topic><topic>Laboratories</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>Medical records</topic><topic>Medical research</topic><topic>Medicine, Research & Experimental</topic><topic>Mortality</topic><topic>Mucopurulent secretions</topic><topic>Nebulizers and Vaporizers</topic><topic>Neutrophil extracellular traps</topic><topic>Neutrophils</topic><topic>Pandemics</topic><topic>Patients</topic><topic>Pneumonia, Viral - drug therapy</topic><topic>Pneumonia, Viral - therapy</topic><topic>Recombinant Proteins - administration & dosage</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Research & Experimental Medicine</topic><topic>Respiration, Artificial</topic><topic>SARS-CoV-2</topic><topic>Science & Technology</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Short Report</topic><topic>Systemic diseases</topic><topic>Thrombosis</topic><topic>Ventilators</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Weber, Andrew G.</creatorcontrib><creatorcontrib>Chau, Alice S.</creatorcontrib><creatorcontrib>Egeblad, Mikala</creatorcontrib><creatorcontrib>Barnes, Betsy J.</creatorcontrib><creatorcontrib>Janowitz, Tobias</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale Academic OneFile</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Molecular Medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weber, Andrew G.</au><au>Chau, Alice S.</au><au>Egeblad, Mikala</au><au>Barnes, Betsy J.</au><au>Janowitz, Tobias</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series</atitle><jtitle>Molecular Medicine</jtitle><stitle>MOL MED</stitle><addtitle>Mol Med</addtitle><date>2020-09-29</date><risdate>2020</risdate><volume>26</volume><issue>1</issue><spage>91</spage><epage>91</epage><pages>91-91</pages><artnum>91</artnum><issn>1076-1551</issn><eissn>1528-3658</eissn><abstract>Background Mechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system. Methods Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed. Results The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified. Conclusions Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.</abstract><cop>NEW YORK</cop><pub>Springer Nature</pub><pmid>32993479</pmid><doi>10.1186/s10020-020-00215-w</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-6766-4352</orcidid><orcidid>https://orcid.org/0000-0001-9800-3709</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Albuterol - administration & dosage Albuterol - therapeutic use Biochemistry & Molecular Biology Body mass index Bronchodilator Agents - administration & dosage Bronchodilator Agents - therapeutic use Cell Biology Coronavirus Coronavirus Infections - drug therapy Coronavirus Infections - therapy Coronaviruses COVID-19 Dehydrogenases Deoxyribonuclease I - administration & dosage Deoxyribonuclease I - therapeutic use Dornase alfa Extracorporeal membrane oxygenation Female Health aspects Hemoptysis Hispanic people Humans Hypertension Intensive care Intubation Intubation, Intratracheal Laboratories Life Sciences & Biomedicine Male Medical records Medical research Medicine, Research & Experimental Mortality Mucopurulent secretions Nebulizers and Vaporizers Neutrophil extracellular traps Neutrophils Pandemics Patients Pneumonia, Viral - drug therapy Pneumonia, Viral - therapy Recombinant Proteins - administration & dosage Recombinant Proteins - therapeutic use Research & Experimental Medicine Respiration, Artificial SARS-CoV-2 Science & Technology Severe acute respiratory syndrome coronavirus 2 Short Report Systemic diseases Thrombosis Ventilators |
| title | Nebulized in-line endotracheal dornase alfa and albuterol administered to mechanically ventilated COVID-19 patients: a case series |
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