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===High Flow Nasal Cannula (HFNC)===
===High Flow Nasal Cannula (HFNC)===
*Also known as high flow nasal oxygen (HFNO) or Heated humidified high-flow (HHHF) therapy.
*Also known as high flow nasal oxygen (HFNO) or Heated humidified high-flow (HHHF) therapy is a non-invasive technique.
*Surviving Sepsis Campaign has the following recommendations regarding the use of HFNC in [[COVID-19]] patients:<ref name="AlhazzaniMøller2020">{{cite journal|last1=Alhazzani|first1=Waleed|last2=Møller|first2=Morten Hylander|last3=Arabi|first3=Yaseen M.|last4=Loeb|first4=Mark|last5=Gong|first5=Michelle Ng|last6=Fan|first6=Eddy|last7=Oczkowski|first7=Simon|last8=Levy|first8=Mitchell M.|last9=Derde|first9=Lennie|last10=Dzierba|first10=Amy|last11=Du|first11=Bin|last12=Aboodi|first12=Michael|last13=Wunsch|first13=Hannah|last14=Cecconi|first14=Maurizio|last15=Koh|first15=Younsuck|last16=Chertow|first16=Daniel S.|last17=Maitland|first17=Kathryn|last18=Alshamsi|first18=Fayez|last19=Belley-Cote|first19=Emilie|last20=Greco|first20=Massimiliano|last21=Laundy|first21=Matthew|last22=Morgan|first22=Jill S.|last23=Kesecioglu|first23=Jozef|last24=McGeer|first24=Allison|last25=Mermel|first25=Leonard|last26=Mammen|first26=Manoj J.|last27=Alexander|first27=Paul E.|last28=Arrington|first28=Amy|last29=Centofanti|first29=John E.|last30=Citerio|first30=Giuseppe|last31=Baw|first31=Bandar|last32=Memish|first32=Ziad A.|last33=Hammond|first33=Naomi|last34=Hayden|first34=Frederick G.|last35=Evans|first35=Laura|last36=Rhodes|first36=Andrew|title=Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)|journal=Critical Care Medicine|volume=48|issue=6|year=2020|pages=e440–e469|issn=0090-3493|doi=10.1097/CCM.0000000000004363}}</ref>
*Surviving Sepsis Campaign has the following recommendations regarding the use of HFNC in [[COVID-19]] patients:<ref name="AlhazzaniMøller2020">{{cite journal|last1=Alhazzani|first1=Waleed|last2=Møller|first2=Morten Hylander|last3=Arabi|first3=Yaseen M.|last4=Loeb|first4=Mark|last5=Gong|first5=Michelle Ng|last6=Fan|first6=Eddy|last7=Oczkowski|first7=Simon|last8=Levy|first8=Mitchell M.|last9=Derde|first9=Lennie|last10=Dzierba|first10=Amy|last11=Du|first11=Bin|last12=Aboodi|first12=Michael|last13=Wunsch|first13=Hannah|last14=Cecconi|first14=Maurizio|last15=Koh|first15=Younsuck|last16=Chertow|first16=Daniel S.|last17=Maitland|first17=Kathryn|last18=Alshamsi|first18=Fayez|last19=Belley-Cote|first19=Emilie|last20=Greco|first20=Massimiliano|last21=Laundy|first21=Matthew|last22=Morgan|first22=Jill S.|last23=Kesecioglu|first23=Jozef|last24=McGeer|first24=Allison|last25=Mermel|first25=Leonard|last26=Mammen|first26=Manoj J.|last27=Alexander|first27=Paul E.|last28=Arrington|first28=Amy|last29=Centofanti|first29=John E.|last30=Citerio|first30=Giuseppe|last31=Baw|first31=Bandar|last32=Memish|first32=Ziad A.|last33=Hammond|first33=Naomi|last34=Hayden|first34=Frederick G.|last35=Evans|first35=Laura|last36=Rhodes|first36=Andrew|title=Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)|journal=Critical Care Medicine|volume=48|issue=6|year=2020|pages=e440–e469|issn=0090-3493|doi=10.1097/CCM.0000000000004363}}</ref>
**In [[COVID-19]] positive adult [[patients]] with acute [[respiratory failure|hypoxemic respiratory failure]] despite [[oxygen therapy|supplemental oxygen therapy]], a weak recommendation suggests using HFNC over conventional [[oxygen therapy]]. A systematic review and meta-analysis of 9 [[Randomized controlled trial|RCTs]] showed that High Flow Nasal Cannula (HFNC) reduces the need for [[intubation]].
**In [[COVID-19]] positive adult [[patients]] with acute [[respiratory failure|hypoxemic respiratory failure]] despite [[oxygen therapy|supplemental oxygen therapy]], a weak recommendation suggests using HFNC over conventional [[oxygen therapy]]. A systematic review and meta-analysis of 9 [[Randomized controlled trial|RCTs]] showed that High Flow Nasal Cannula (HFNC) reduces the need for [[intubation]].
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**[[Patient]] should be monitored closely and [[intubated]] in the event of decompensation.  
**[[Patient]] should be monitored closely and [[intubated]] in the event of decompensation.  


==Mechanical Ventilation==
===Non-Invasive Positive Pressure Ventilation===
===Non-Invasive Positive Pressure Ventilation===
*[[Positive airway pressure|Non-invasive positive pressure ventilation (NIPPV)]] is a technique utilized for delivering mechanical ventilation without the use of [[endotracheal intubation]] or [[tracheostomy]]. It can be administered through a [[Oxygen mask|face mask]], nasal mask, or a helmet.  
*[[Positive airway pressure|Non-invasive positive pressure ventilation (NIPPV)]] is a technique utilized for delivering mechanical ventilation without the use of [[endotracheal intubation]] or [[tracheostomy]]. It can be administered through a [[Oxygen mask|face mask]], nasal mask, or a helmet (not recommended in [[COVID-19]] care due to potential aerosol transmission of the [[SARS-CoV-2|severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)]].
*Many patients who develop [[ARDS]] receive a trial of [[Positive airway pressure|non-invasive positive pressure ventilation (NIPPV)]] before [[intubation]] for [[mechanical ventilation]] before they clinically deteriorate or become unable to maintain adequate [[oxygenation]].
*Many patients who develop [[ARDS]] receive a trial of [[Positive airway pressure|non-invasive positive pressure ventilation (NIPPV)]] before [[intubation]] for [[mechanical ventilation]] before they clinically deteriorate or become unable to maintain adequate [[oxygenation]].
*Studies from China reported (4% to 13%) of [[COVID-19]] patients to have received [[Positive airway pressure|non-invasive positive pressure ventilation (NIPPV)]].<ref name="AlhazzaniMøller2020">{{cite journal|last1=Alhazzani|first1=Waleed|last2=Møller|first2=Morten Hylander|last3=Arabi|first3=Yaseen M.|last4=Loeb|first4=Mark|last5=Gong|first5=Michelle Ng|last6=Fan|first6=Eddy|last7=Oczkowski|first7=Simon|last8=Levy|first8=Mitchell M.|last9=Derde|first9=Lennie|last10=Dzierba|first10=Amy|last11=Du|first11=Bin|last12=Aboodi|first12=Michael|last13=Wunsch|first13=Hannah|last14=Cecconi|first14=Maurizio|last15=Koh|first15=Younsuck|last16=Chertow|first16=Daniel S.|last17=Maitland|first17=Kathryn|last18=Alshamsi|first18=Fayez|last19=Belley-Cote|first19=Emilie|last20=Greco|first20=Massimiliano|last21=Laundy|first21=Matthew|last22=Morgan|first22=Jill S.|last23=Kesecioglu|first23=Jozef|last24=McGeer|first24=Allison|last25=Mermel|first25=Leonard|last26=Mammen|first26=Manoj J.|last27=Alexander|first27=Paul E.|last28=Arrington|first28=Amy|last29=Centofanti|first29=John E.|last30=Citerio|first30=Giuseppe|last31=Baw|first31=Bandar|last32=Memish|first32=Ziad A.|last33=Hammond|first33=Naomi|last34=Hayden|first34=Frederick G.|last35=Evans|first35=Laura|last36=Rhodes|first36=Andrew|title=Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)|journal=Critical Care Medicine|volume=48|issue=6|year=2020|pages=e440–e469|issn=0090-3493|doi=10.1097/CCM.0000000000004363}}</ref>
*Studies from China reported (4% to 13%) of [[COVID-19]] patients to have received [[Positive airway pressure|non-invasive positive pressure ventilation (NIPPV)]].<ref name="AlhazzaniMøller2020">{{cite journal|last1=Alhazzani|first1=Waleed|last2=Møller|first2=Morten Hylander|last3=Arabi|first3=Yaseen M.|last4=Loeb|first4=Mark|last5=Gong|first5=Michelle Ng|last6=Fan|first6=Eddy|last7=Oczkowski|first7=Simon|last8=Levy|first8=Mitchell M.|last9=Derde|first9=Lennie|last10=Dzierba|first10=Amy|last11=Du|first11=Bin|last12=Aboodi|first12=Michael|last13=Wunsch|first13=Hannah|last14=Cecconi|first14=Maurizio|last15=Koh|first15=Younsuck|last16=Chertow|first16=Daniel S.|last17=Maitland|first17=Kathryn|last18=Alshamsi|first18=Fayez|last19=Belley-Cote|first19=Emilie|last20=Greco|first20=Massimiliano|last21=Laundy|first21=Matthew|last22=Morgan|first22=Jill S.|last23=Kesecioglu|first23=Jozef|last24=McGeer|first24=Allison|last25=Mermel|first25=Leonard|last26=Mammen|first26=Manoj J.|last27=Alexander|first27=Paul E.|last28=Arrington|first28=Amy|last29=Centofanti|first29=John E.|last30=Citerio|first30=Giuseppe|last31=Baw|first31=Bandar|last32=Memish|first32=Ziad A.|last33=Hammond|first33=Naomi|last34=Hayden|first34=Frederick G.|last35=Evans|first35=Laura|last36=Rhodes|first36=Andrew|title=Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)|journal=Critical Care Medicine|volume=48|issue=6|year=2020|pages=e440–e469|issn=0090-3493|doi=10.1097/CCM.0000000000004363}}</ref>
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The Chinese [[CDC]] reports the case-fatality rate to be higher than 50% in [[patients]] who received invasive mechanical ventilation.<ref name="WuMcGoogan2020">{{cite journal|last1=Wu|first1=Zunyou|last2=McGoogan|first2=Jennifer M.|title=Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China|journal=JAMA|volume=323|issue=13|year=2020|pages=1239|issn=0098-7484|doi=10.1001/jama.2020.2648}}</ref>
The Chinese [[CDC]] reports the case-fatality rate to be higher than 50% in [[patients]] who received invasive mechanical ventilation.<ref name="WuMcGoogan2020">{{cite journal|last1=Wu|first1=Zunyou|last2=McGoogan|first2=Jennifer M.|title=Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China|journal=JAMA|volume=323|issue=13|year=2020|pages=1239|issn=0098-7484|doi=10.1001/jama.2020.2648}}</ref>


=== Alternative Mechanical Ventilation Strategies ===
Several specialized modes of [[mechanical ventilation]] have been tested in ARDS, however, none has been proven to carry a [[morbidity]] or [[mortality]] benefit and should only be considered if [[oxygenation]] does not improve with a judicious trial of the first-line mechanical [[ventilation strategies]] as outlined by the ARDS Network.<ref>NIH-NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary. "http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf"</ref>
*[[Mechanical ventilation modes of ventilation#High Frequency Ventilation (HFV)|'''High-frequency oscillatory ventilation (HFOV)''']] may improve [[oxygenation]] in patients with '''[[Acute respiratory distress syndrome diagnostic criteria|moderate to severe ARDS]] and severe refractory [[hypoxemia]]''', however, initiation of HFOV early in the course of ARDS (i.e., prior to low [[tidal volume]]/high [[PEEP]] [[mechanical ventilation]]) has been associated with ''increased mortality'' compared to lower [[tidal volume]]/high [[PEEP]] ventilation<ref name="pmid12231488">{{cite journal| author=Derdak S, Mehta S, Stewart TE, Smith T, Rogers M, Buchman TG et al.| title=High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. | journal=Am J Respir Crit Care Med | year= 2002 | volume= 166 | issue= 6 | pages= 801-8 | pmid=12231488 | doi=10.1164/rccm.2108052 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12231488  }} </ref><ref name="pmid23339639">{{cite journal| author=Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P et al.| title=High-frequency oscillation in early acute respiratory distress syndrome. | journal=N Engl J Med | year= 2013 | volume= 368 | issue= 9 | pages= 795-805 | pmid=23339639 | doi=10.1056/NEJMoa1215554 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23339639  }} </ref>
*'''[[Acute respiratory distress syndrome mechanical ventilation therapy#APRV (Airway Pressure Release Ventilation) and ARDS / ALI |Airway pressure release ventilation (APRV)]]''' appears to be safe in ARDS, and may be associated with reduced [[paralytic]] and [[sedative]] use as well as an increase in the number of ventilator-free days<ref name="pmid19727373">{{cite journal| author=Daoud EG| title=Airway pressure release ventilation. | journal=Ann Thorac Med | year= 2007 | volume= 2 | issue= 4 | pages= 176-9 | pmid=19727373 | doi=10.4103/1817-1737.36556 | pmc=2732103 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19727373  }} </ref><ref name="pmid21762559">{{cite journal| author=Daoud EG, Farag HL, Chatburn RL| title=Airway pressure release ventilation: what do we know? | journal=Respir Care | year= 2012 | volume= 57 | issue= 2 | pages= 282-92 | pmid=21762559 | doi=10.4187/respcare.01238 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21762559  }} </ref>
===Recruitment Maneuvers===
A '''recruitment maneuver''' is the application of very high (up to 40 cm H<sub>2</sub>O) positive airway pressure to open collapsed [[alveolus|alveoli]], thereby reducing [[Shunt|shunting]], decreasing [[Ventilation-perfusion mismatch|V/Q mismatching]], and improving [[gas exchange]]. The decision to apply recruitment maneuvers must take into account various factors including the extent of lung injury (due to the risk of causing [[barotrauma|volutrauma]] through overdistention of stiff and inflamed lungs) and patient [[hemodynamics]] (due to the risk of further worsening [[hypotension]] by impeding [[venous return]] to the [[right heart]]). Recruitment maneuvers have not been standardized and there are insufficient data to support or discourage their use in ARDS.
=== Extracorporeal Membrane Oxygenation (ECMO) ===
There is growing evidence to support the use of [[extracorporeal membrane oxygenation|extracorporeal membrane oxygenation (ECMO)]] for severe ARDS that fails to improve despite judicious application of the ARDS Network low tidal volume/high PEEP ventilation strategy.<ref name="pmid3090285">{{cite journal| author=Gattinoni L, Pesenti A, Mascheroni D, Marcolin R, Fumagalli R, Rossi F et al.| title=Low-frequency positive-pressure ventilation with extracorporeal CO2 removal in severe acute respiratory failure. | journal=JAMA | year= 1986 | volume= 256 | issue= 7 | pages= 881-6 | pmid=3090285 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3090285  }} </ref><ref name="pmid19762075">{{cite journal| author=Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM et al.| title=Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. | journal=Lancet | year= 2009 | volume= 374 | issue= 9698 | pages= 1351-63 | pmid=19762075 | doi=10.1016/S0140-6736(09)61069-2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19762075  }} </ref> ECMO facilitates gas exchange in circumstances where adequate oxygenation and ventilation cannot be achieved through the lungs themselves. There are two main forms of ECMO, both of which have been used successfully in the treatment of [[Acute respiratory distress syndrome diagnostic criteria|severe ARDS]]:
*'''Veno-venous (VV)-ECMO''': [[Venous blood]] is removed through an outflow [[cannula]] placed in a large [[vein]] (usually the right [[femoral vein]] or [[inferior vena cava]]) and passed through an [[oxygenator]] where [[gas exchange]] occurs (CO<sub>2</sub> is removed and O<sub>2</sub> is introduced) before being returned to the body through an inflow cannula placed in another large vein (usually the right [[internal jugular vein]] or [[superior vena cava]])
:*Supports [[gas exchange]] but does not provide any [[hemodynamic]] support
*'''Veno-arterial (VA)-ECMO''': Venous blood is removed through an outflow [[cannula]] placed in a large [[vein]] (usually the right femoral vein or inferior vena cava) and passed through an oxygenator where [[gas exchange]] occurs (CO<sub>2</sub> is removed and O<sub>2</sub> is introduced) before being returned to the body through an inflow cannula placed in a large [[artery]] (usually the right [[femoral artery]] or right [[carotid artery]])
:*Supports [[gas exchange]] and provides [[hemodynamic]] support by bypassing the heart completely
The use of ECMO in the treatment of ARDS is an ongoing area of research, and referral to a medical center with ample experience in the use of ECMO for ARDS should be considered for patients with ARDS who are failing traditional management strategies and may be candidates for ECMO. The use of ECMO requires systemic [[anticoagulation]] (usually with [[heparin]]) and is associated with the risk of major [[hemorrhage]] as well as [[thrombosis]]. Additionally, the use of VA-ECMO may result in [[Ischemia|ischemic injury]] to the limb [[distal]] to the site of the inflow [[cannula]] (although rates of limb ischemia have been mitigated by the addition of a [[reperfusion]] cannula that takes blood from the inflow cannula and delivers it distally to the otherwise-affected limb).




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Marini et al. suggest  
Marini et al. suggest  
**Lower PEEP: “type L,” characterized by low lung elastance (high compliance), lower lung weight as estimated by CT scan, and a low response to PEEP  
**Lower PEEP: “type L,” characterized by low lung elastance (high compliance), lower lung weight as estimated by CT scan, and a low response to PEEP  
**Higher PEEP:   
**Higher PEEP: Initially it was recommended that the guidelines for [[ARDS]] must be followed for respiratory support in [[COVID-19|SARS Cov2]] patients. But the data from China helped inform and reform regarding the strategies. '''In Wuhan, patients with acute hypoxemic respiratory failure due to COVID-19 have a poor tolerance to high PEEP, likely as the result of the direct and severe lung damage by the virus and inflammatory reactions.'''<ref name="MengQiu2020">{{cite journal|last1=Meng|first1=Lingzhong|last2=Qiu|first2=Haibo|last3=Wan|first3=Li|last4=Ai|first4=Yuhang|last5=Xue|first5=Zhanggang|last6=Guo|first6=Qulian|last7=Deshpande|first7=Ranjit|last8=Zhang|first8=Lina|last9=Meng|first9=Jie|last10=Tong|first10=Chuanyao|last11=Liu|first11=Hong|last12=Xiong|first12=Lize|title=Intubation and Ventilation amid the COVID-19 Outbreak|journal=Anesthesiology|volume=132|issue=6|year=2020|pages=1317–1332|issn=0003-3022|doi=10.1097/ALN.0000000000003296}}</ref>
*it may be best to avoid high-frequency oscillatory ventilation in patients with COVID-19 due to concerns of aerosol generation.19,37,38  
*'''Lower [[Lung volume|tidal volume]] [[Mechanical ventilation|ventilation]]''' (6 mL/kg predicted body weight) is associated with reduced mortality and a greater number of ventilator-free days<ref name="pmid10793162">{{cite journal| author=| title=Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. | journal=N Engl J Med | year= 2000 | volume= 342 | issue= 18 | pages= 1301-8 | pmid=10793162 | doi=10.1056/NEJM200005043421801 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10793162  }} </ref>
*'''Lower [[Lung volume|tidal volume]] [[Mechanical ventilation|ventilation]]''' (6 mL/kg predicted body weight) is associated with reduced mortality and a greater number of ventilator-free days<ref name="pmid10793162">{{cite journal| author=| title=Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network. | journal=N Engl J Med | year= 2000 | volume= 342 | issue= 18 | pages= 1301-8 | pmid=10793162 | doi=10.1056/NEJM200005043421801 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10793162  }} </ref>
:*Lower tidal volume ventilation should be continued even if the [[PaCO2|arterial partial pressure of carbon dioxide (PaCO<sub>2</sub>)]] rises (this is called ''permissive [[hypercapnia]]'')
:*Lower tidal volume ventilation should be continued even if the [[PaCO2|arterial partial pressure of carbon dioxide (PaCO<sub>2</sub>)]] rises (this is called ''permissive [[hypercapnia]]'')
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::*PBW (women) = '''45.5 + 2.3 (height in inches – 60)'''
::*PBW (women) = '''45.5 + 2.3 (height in inches – 60)'''
*'''Higher [[positive end-expiratory pressure|positive end-expiratory pressure (PEEP)]]''' combined with lower tidal volume ventilation is associated with decreased mortality in patients with '''moderate or severe ARDS (PaO<sub>2</sub>/FIO<sub>2</sub> ≤ 200)'''<ref name="pmid20197533">{{cite journal| author=Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD et al.| title=Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. | journal=JAMA | year= 2010 | volume= 303 | issue= 9 | pages= 865-73 | pmid=20197533 | doi=10.1001/jama.2010.218 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20197533  }} </ref>
*'''Higher [[positive end-expiratory pressure|positive end-expiratory pressure (PEEP)]]''' combined with lower tidal volume ventilation is associated with decreased mortality in patients with '''moderate or severe ARDS (PaO<sub>2</sub>/FIO<sub>2</sub> ≤ 200)'''<ref name="pmid20197533">{{cite journal| author=Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD et al.| title=Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis. | journal=JAMA | year= 2010 | volume= 303 | issue= 9 | pages= 865-73 | pmid=20197533 | doi=10.1001/jama.2010.218 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20197533  }} </ref>
*'''[[Mechanical ventilation initial ventilator settings#Proning|Prone positioning''']] for at least 16 consecutive hours each day is associated with improved 28-day and 90-day survival in patients with '''ARDS and a PaO<sub>2</sub>/FIO<sub>2</sub> ratio < 150 on an FIO<sub>2</sub> ≥ 60% and PEEP ≥ 5 mmHg'''
:*Prone positioning is thought to improve [[oxygenation]] by improving [[Ventilation/perfusion ratio|ventilation/perfusion (V/Q) mismatching]] via reduced [[Shunt|shunting of blood]] through under-ventilated lung tissue
*'''[[Cisatracurium]]''', when started within the first 48 hours of ARDS diagnosis and continued for 48 hours, has been associated with improved 90-day survival, a greater number of ventilator-free days, and a decreased incidence of [[barotrauma|volutrauma]]<ref name="pmid20843245">{{cite journal| author=Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A et al.| title=Neuromuscular blockers in early acute respiratory distress syndrome. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 12 | pages= 1107-16 | pmid=20843245 | doi=10.1056/NEJMoa1005372 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20843245  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21242357 Review in: Ann Intern Med. 2011 Jan 18;154(2):JC1-3] </ref>
*'''[[Cisatracurium]]''', when started within the first 48 hours of ARDS diagnosis and continued for 48 hours, has been associated with improved 90-day survival, a greater number of ventilator-free days, and a decreased incidence of [[barotrauma|volutrauma]]<ref name="pmid20843245">{{cite journal| author=Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A et al.| title=Neuromuscular blockers in early acute respiratory distress syndrome. | journal=N Engl J Med | year= 2010 | volume= 363 | issue= 12 | pages= 1107-16 | pmid=20843245 | doi=10.1056/NEJMoa1005372 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20843245  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21242357 Review in: Ann Intern Med. 2011 Jan 18;154(2):JC1-3] </ref>


=== ARDS Network Mechanical Ventilation Protocol ===
=== ARDS Network Mechanical Ventilation Protocol ===
==Intubation==
According to the American Society of Anesthesiology based upon the experience of Chinese anesthesiologists, timely (neither premature nor late) [[intubation]] and ventilation most effectual breathing assistance.<ref name="urlStrategies for health care response to COVID-19 shared by Chinese anesthesiologists">{{cite web |url=https://www.asahq.org/about-asa/newsroom/news-releases/2020/03/strategies-for-health-care-response-to-covid-19-shared-by-chinese-anesthesiologists |title=Strategies for health care response to COVID-19 shared by Chinese anesthesiologists |format= |work= |accessdate=}}</ref>
<ref name="MengQiu2020">{{cite journal|last1=Meng|first1=Lingzhong|last2=Qiu|first2=Haibo|last3=Wan|first3=Li|last4=Ai|first4=Yuhang|last5=Xue|first5=Zhanggang|last6=Guo|first6=Qulian|last7=Deshpande|first7=Ranjit|last8=Zhang|first8=Lina|last9=Meng|first9=Jie|last10=Tong|first10=Chuanyao|last11=Liu|first11=Hong|last12=Xiong|first12=Lize|title=Intubation and Ventilation amid the COVID-19 Outbreak|journal=Anesthesiology|volume=132|issue=6|year=2020|pages=1317–1332|issn=0003-3022|doi=10.1097/ALN.0000000000003296}}</ref>
_The widely used practice in Wuhan, after lung recruitment maneuvers, is to set PEEP at 20 cm H2O and titrate down in a decrement of 2 to 3 cm H2O each time until the goals of oxygenation, plateau pressure, and compliance are all achieved. The commonly used PEEP in this patient population is less than 10 cm H2O.
-No mode of ventilation has been suggested to be superior to others.
===Stratagies to improve oxygenation===
====[[Mechanical ventilation initial ventilator settings#Proning|Prone position]] ventilation====
*[[Mechanical ventilation initial ventilator settings#Proning|Prone positioning]] is thought to improve oxygenation by improving [[Ventilation-perfusion mismatch|ventilation/perfusion (V/Q) mismatching]] via reduced shunting of blood through under-ventilated lung tissue.
*Research has shown that [[prone position]] ventilation in [[ARDS]] patients with acute hypoxemic [[respiratory failure]] and spontaneous or assisted breathing reduces the mortality by (28 and 90-days).<ref name="pmid29576824">{{cite journal |vauthors=Xie H, Zhou ZG, Jin W, Yuan CB, Du J, Lu J, Wang RL |title=Ventilator management for acute respiratory distress syndrome associated with avian influenza A (H7N9) virus infection: A case series |journal=World J Emerg Med |volume=9 |issue=2 |pages=118–124 |date=2018 |pmid=29576824 |pmc=5847497 |doi=10.5847/wjem.j.1920-8642.2018.02.006 |url=}}</ref>
The strategy was widely used in [[COVID-19]] patients in Wuhan, China.<ref name="MengQiu2020">{{cite journal|last1=Meng|first1=Lingzhong|last2=Qiu|first2=Haibo|last3=Wan|first3=Li|last4=Ai|first4=Yuhang|last5=Xue|first5=Zhanggang|last6=Guo|first6=Qulian|last7=Deshpande|first7=Ranjit|last8=Zhang|first8=Lina|last9=Meng|first9=Jie|last10=Tong|first10=Chuanyao|last11=Liu|first11=Hong|last12=Xiong|first12=Lize|title=Intubation and Ventilation amid the COVID-19 Outbreak|journal=Anesthesiology|volume=132|issue=6|year=2020|pages=1317–1332|issn=0003-3022|doi=10.1097/ALN.0000000000003296}}</ref>
*[[Mechanical ventilation initial ventilator settings#Proning|Prone position]] is an early strategy rather than a desperate rescue therapy.<ref name="TeliasKatira2020">{{cite journal|last1=Telias|first1=Irene|last2=Katira|first2=Bhushan H.|last3=Brochard|first3=Laurent|title=Is the Prone Position Helpful During Spontaneous Breathing in Patients With COVID-19?|journal=JAMA|volume=323|issue=22|year=2020|pages=2265|issn=0098-7484|doi=10.1001/jama.2020.8539}}</ref> A study by Lin Ding et al. suggests that the early application of prone ventilation with HFNC and NIV, especially in [[COVID-19]] patients with moderate [[ARDS]], can help avoid intubation.<ref name="pmid32000806">{{cite journal |vauthors=Ding L, Wang L, Ma W, He H |title=Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study |journal=Crit Care |volume=24 |issue=1 |pages=28 |date=January 2020 |pmid=32000806 |pmc=6993481 |doi=10.1186/s13054-020-2738-5 |url=}}</ref>
* [[Mechanical ventilation initial ventilator settings#Proning|Prone position]] for awake, spontaneously breathing patients with COVID-19 severe hypoxemic [[respiratory failure]] was associated with improved oxygenation. In addition, patients with an Spo2 of 95% or greater after 1 hour of the [[Mechanical ventilation initial ventilator settings#Proning|Prone position]] was associated with a lower rate of intubation. <ref name="ThompsonRanard2020">{{cite journal|last1=Thompson|first1=Alison E.|last2=Ranard|first2=Benjamin L.|last3=Wei|first3=Ying|last4=Jelic|first4=Sanja|title=Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure|journal=JAMA Internal Medicine|year=2020|issn=2168-6106|doi=10.1001/jamainternmed.2020.3030}}</ref>
*The American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice and Surviving Sepsis Campaign guidelines strongly recommend (moderate evidence) [[Mechanical ventilation initial ventilator settings#Proning|Prone positioning]] for more than 12 hours/day in patients with severe [[ARDS]].<ref name="FanDel Sorbo2017">{{cite journal|last1=Fan|first1=Eddy|last2=Del Sorbo|first2=Lorenzo|last3=Goligher|first3=Ewan C.|last4=Hodgson|first4=Carol L.|last5=Munshi|first5=Laveena|last6=Walkey|first6=Allan J.|last7=Adhikari|first7=Neill K. J.|last8=Amato|first8=Marcelo B. P.|last9=Branson|first9=Richard|last10=Brower|first10=Roy G.|last11=Ferguson|first11=Niall D.|last12=Gajic|first12=Ognjen|last13=Gattinoni|first13=Luciano|last14=Hess|first14=Dean|last15=Mancebo|first15=Jordi|last16=Meade|first16=Maureen O.|last17=McAuley|first17=Daniel F.|last18=Pesenti|first18=Antonio|last19=Ranieri|first19=V. Marco|last20=Rubenfeld|first20=Gordon D.|last21=Rubin|first21=Eileen|last22=Seckel|first22=Maureen|last23=Slutsky|first23=Arthur S.|last24=Talmor|first24=Daniel|last25=Thompson|first25=B. Taylor|last26=Wunsch|first26=Hannah|last27=Uleryk|first27=Elizabeth|last28=Brozek|first28=Jan|last29=Brochard|first29=Laurent J.|title=An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome|journal=American Journal of Respiratory and Critical Care Medicine|volume=195|issue=9|year=2017|pages=1253–1263|issn=1073-449X|doi=10.1164/rccm.201703-0548ST}}</ref><ref name="RhodesEvans2017">{{cite journal|last1=Rhodes|first1=Andrew|last2=Evans|first2=Laura E.|last3=Alhazzani|first3=Waleed|last4=Levy|first4=Mitchell M.|last5=Antonelli|first5=Massimo|last6=Ferrer|first6=Ricard|last7=Kumar|first7=Anand|last8=Sevransky|first8=Jonathan E.|last9=Sprung|first9=Charles L.|last10=Nunnally|first10=Mark E.|last11=Rochwerg|first11=Bram|last12=Rubenfeld|first12=Gordon D.|last13=Angus|first13=Derek C.|last14=Annane|first14=Djillali|last15=Beale|first15=Richard J.|last16=Bellinghan|first16=Geoffrey J.|last17=Bernard|first17=Gordon R.|last18=Chiche|first18=Jean-Daniel|last19=Coopersmith|first19=Craig|last20=De Backer|first20=Daniel P.|last21=French|first21=Craig J.|last22=Fujishima|first22=Seitaro|last23=Gerlach|first23=Herwig|last24=Hidalgo|first24=Jorge Luis|last25=Hollenberg|first25=Steven M.|last26=Jones|first26=Alan E.|last27=Karnad|first27=Dilip R.|last28=Kleinpell|first28=Ruth M.|last29=Koh|first29=Younsuk|last30=Lisboa|first30=Thiago Costa|last31=Machado|first31=Flavia R.|last32=Marini|first32=John J.|last33=Marshall|first33=John C.|last34=Mazuski|first34=John E.|last35=McIntyre|first35=Lauralyn A.|last36=McLean|first36=Anthony S.|last37=Mehta|first37=Sangeeta|last38=Moreno|first38=Rui P.|last39=Myburgh|first39=John|last40=Navalesi|first40=Paolo|last41=Nishida|first41=Osamu|last42=Osborn|first42=Tiffany M.|last43=Perner|first43=Anders|last44=Plunkett|first44=Colleen M.|last45=Ranieri|first45=Marco|last46=Schorr|first46=Christa A.|last47=Seckel|first47=Maureen A.|last48=Seymour|first48=Christopher W.|last49=Shieh|first49=Lisa|last50=Shukri|first50=Khalid A.|last51=Simpson|first51=Steven Q.|last52=Singer|first52=Mervyn|last53=Thompson|first53=B. Taylor|last54=Townsend|first54=Sean R.|last55=Van der Poll|first55=Thomas|last56=Vincent|first56=Jean-Louis|last57=Wiersinga|first57=W. Joost|last58=Zimmerman|first58=Janice L.|last59=Dellinger|first59=R. Phillip|title=Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016|journal=Intensive Care Medicine|volume=43|issue=3|year=2017|pages=304–377|issn=0342-4642|doi=10.1007/s00134-017-4683-6}}</ref>
====Lung recruitment maneauvers====




Revision as of 12:59, 18 July 2020

Mechanical ventilation



Ventilatory support

Supplemental Oxygen

  • Surviving Sepsis Campaign has the following recommendations regarding the use of supplemental oxygen in COVID-19 patients:[1]
    • It is strongly recommended (with moderate-quality evidence) to start the supplemental oxygen if the Spo2 is < 90% in adults. A weak recommendation states starting the supplemental oxygen at < 92% saturation.
    • In COVID-19 positive adult patients with acute hypoxemic respiratory failure on supplemental oxygen therapy, Spo2 should be maintained no higher than 96% (strong recommendation by Surviving Sepsis Campaign). This based upon the systematic review and meta-analysis of 25 RCTs that showed a linear association between the death risk and higher Spo2 targets.

High Flow Nasal Cannula (HFNC)

Mechanical Ventilation

Non-Invasive Positive Pressure Ventilation

Invasive mechanical ventilation The Chinese CDC reports the case-fatality rate to be higher than 50% in patients who received invasive mechanical ventilation.[3]


The vascular endothelial injury in CARDS and diverse mortality rates across the world in CARDS patients arbitrates the importance of different mechanical ventilation strategies. Marini et al. suggest

    • Lower PEEP: “type L,” characterized by low lung elastance (high compliance), lower lung weight as estimated by CT scan, and a low response to PEEP
    • Higher PEEP: Initially it was recommended that the guidelines for ARDS must be followed for respiratory support in SARS Cov2 patients. But the data from China helped inform and reform regarding the strategies. In Wuhan, patients with acute hypoxemic respiratory failure due to COVID-19 have a poor tolerance to high PEEP, likely as the result of the direct and severe lung damage by the virus and inflammatory reactions.[4]
  • it may be best to avoid high-frequency oscillatory ventilation in patients with COVID-19 due to concerns of aerosol generation.19,37,38
  • Lower tidal volume ventilation (6 mL/kg predicted body weight) is associated with reduced mortality and a greater number of ventilator-free days[5]
  • PBW (men) = 50 + 2.3 (height in inches – 60)
  • PBW (women) = 45.5 + 2.3 (height in inches – 60)
  • Higher positive end-expiratory pressure (PEEP) combined with lower tidal volume ventilation is associated with decreased mortality in patients with moderate or severe ARDS (PaO2/FIO2 ≤ 200)[6]
  • Cisatracurium, when started within the first 48 hours of ARDS diagnosis and continued for 48 hours, has been associated with improved 90-day survival, a greater number of ventilator-free days, and a decreased incidence of volutrauma[7]

ARDS Network Mechanical Ventilation Protocol

Intubation

According to the American Society of Anesthesiology based upon the experience of Chinese anesthesiologists, timely (neither premature nor late) intubation and ventilation most effectual breathing assistance.[8]

[4] _The widely used practice in Wuhan, after lung recruitment maneuvers, is to set PEEP at 20 cm H2O and titrate down in a decrement of 2 to 3 cm H2O each time until the goals of oxygenation, plateau pressure, and compliance are all achieved. The commonly used PEEP in this patient population is less than 10 cm H2O. -No mode of ventilation has been suggested to be superior to others.

Stratagies to improve oxygenation

Prone position ventilation

The strategy was widely used in COVID-19 patients in Wuhan, China.[4]

  • Prone position is an early strategy rather than a desperate rescue therapy.[10] A study by Lin Ding et al. suggests that the early application of prone ventilation with HFNC and NIV, especially in COVID-19 patients with moderate ARDS, can help avoid intubation.[11]
  • Prone position for awake, spontaneously breathing patients with COVID-19 severe hypoxemic respiratory failure was associated with improved oxygenation. In addition, patients with an Spo2 of 95% or greater after 1 hour of the Prone position was associated with a lower rate of intubation. [12]
  • The American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice and Surviving Sepsis Campaign guidelines strongly recommend (moderate evidence) Prone positioning for more than 12 hours/day in patients with severe ARDS.[13][14]


Lung recruitment maneauvers

References

  1. ↑ 1.0 1.1 1.2 Alhazzani, Waleed; Møller, Morten Hylander; Arabi, Yaseen M.; Loeb, Mark; Gong, Michelle Ng; Fan, Eddy; Oczkowski, Simon; Levy, Mitchell M.; Derde, Lennie; Dzierba, Amy; Du, Bin; Aboodi, Michael; Wunsch, Hannah; Cecconi, Maurizio; Koh, Younsuck; Chertow, Daniel S.; Maitland, Kathryn; Alshamsi, Fayez; Belley-Cote, Emilie; Greco, Massimiliano; Laundy, Matthew; Morgan, Jill S.; Kesecioglu, Jozef; McGeer, Allison; Mermel, Leonard; Mammen, Manoj J.; Alexander, Paul E.; Arrington, Amy; Centofanti, John E.; Citerio, Giuseppe; Baw, Bandar; Memish, Ziad A.; Hammond, Naomi; Hayden, Frederick G.; Evans, Laura; Rhodes, Andrew (2020). "Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)". Critical Care Medicine. 48 (6): e440–e469. doi:10.1097/CCM.0000000000004363. ISSN 0090-3493.
  2. ↑ Frat, Jean-Pierre; Thille, Arnaud W.; Mercat, Alain; Girault, Christophe; Ragot, Stéphanie; Perbet, Sébastien; Prat, Gwénael; Boulain, Thierry; Morawiec, Elise; Cottereau, Alice; Devaquet, Jérôme; Nseir, Saad; Razazi, Keyvan; Mira, Jean-Paul; Argaud, Laurent; Chakarian, Jean-Charles; Ricard, Jean-Damien; Wittebole, Xavier; Chevalier, Stéphanie; Herbland, Alexandre; Fartoukh, Muriel; Constantin, Jean-Michel; Tonnelier, Jean-Marie; Pierrot, Marc; Mathonnet, Armelle; Béduneau, Gaëtan; Delétage-Métreau, Céline; Richard, Jean-Christophe M.; Brochard, Laurent; Robert, René (2015). "High-Flow Oxygen through Nasal Cannula in Acute Hypoxemic Respiratory Failure". New England Journal of Medicine. 372 (23): 2185–2196. doi:10.1056/NEJMoa1503326. ISSN 0028-4793.
  3. ↑ Wu, Zunyou; McGoogan, Jennifer M. (2020). "Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China". JAMA. 323 (13): 1239. doi:10.1001/jama.2020.2648. ISSN 0098-7484.
  4. ↑ 4.0 4.1 4.2 Meng, Lingzhong; Qiu, Haibo; Wan, Li; Ai, Yuhang; Xue, Zhanggang; Guo, Qulian; Deshpande, Ranjit; Zhang, Lina; Meng, Jie; Tong, Chuanyao; Liu, Hong; Xiong, Lize (2020). "Intubation and Ventilation amid the COVID-19 Outbreak". Anesthesiology. 132 (6): 1317–1332. doi:10.1097/ALN.0000000000003296. ISSN 0003-3022.
  5. ↑ "Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. The Acute Respiratory Distress Syndrome Network". N Engl J Med. 342 (18): 1301–8. 2000. doi:10.1056/NEJM200005043421801. PMID 10793162.
  6. ↑ Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD; et al. (2010). "Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis". JAMA. 303 (9): 865–73. doi:10.1001/jama.2010.218. PMID 20197533.
  7. ↑ Papazian L, Forel JM, Gacouin A, Penot-Ragon C, Perrin G, Loundou A; et al. (2010). "Neuromuscular blockers in early acute respiratory distress syndrome". N Engl J Med. 363 (12): 1107–16. doi:10.1056/NEJMoa1005372. PMID 20843245. Review in: Ann Intern Med. 2011 Jan 18;154(2):JC1-3
  8. ↑ "Strategies for health care response to COVID-19 shared by Chinese anesthesiologists".
  9. ↑ Xie H, Zhou ZG, Jin W, Yuan CB, Du J, Lu J, Wang RL (2018). "Ventilator management for acute respiratory distress syndrome associated with avian influenza A (H7N9) virus infection: A case series". World J Emerg Med. 9 (2): 118–124. doi:10.5847/wjem.j.1920-8642.2018.02.006. PMC 5847497. PMID 29576824.
  10. ↑ Telias, Irene; Katira, Bhushan H.; Brochard, Laurent (2020). "Is the Prone Position Helpful During Spontaneous Breathing in Patients With COVID-19?". JAMA. 323 (22): 2265. doi:10.1001/jama.2020.8539. ISSN 0098-7484.
  11. ↑ Ding L, Wang L, Ma W, He H (January 2020). "Efficacy and safety of early prone positioning combined with HFNC or NIV in moderate to severe ARDS: a multi-center prospective cohort study". Crit Care. 24 (1): 28. doi:10.1186/s13054-020-2738-5. PMC 6993481 Check |pmc= value (help). PMID 32000806 Check |pmid= value (help).
  12. ↑ Thompson, Alison E.; Ranard, Benjamin L.; Wei, Ying; Jelic, Sanja (2020). "Prone Positioning in Awake, Nonintubated Patients With COVID-19 Hypoxemic Respiratory Failure". JAMA Internal Medicine. doi:10.1001/jamainternmed.2020.3030. ISSN 2168-6106.
  13. ↑ Fan, Eddy; Del Sorbo, Lorenzo; Goligher, Ewan C.; Hodgson, Carol L.; Munshi, Laveena; Walkey, Allan J.; Adhikari, Neill K. J.; Amato, Marcelo B. P.; Branson, Richard; Brower, Roy G.; Ferguson, Niall D.; Gajic, Ognjen; Gattinoni, Luciano; Hess, Dean; Mancebo, Jordi; Meade, Maureen O.; McAuley, Daniel F.; Pesenti, Antonio; Ranieri, V. Marco; Rubenfeld, Gordon D.; Rubin, Eileen; Seckel, Maureen; Slutsky, Arthur S.; Talmor, Daniel; Thompson, B. Taylor; Wunsch, Hannah; Uleryk, Elizabeth; Brozek, Jan; Brochard, Laurent J. (2017). "An Official American Thoracic Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine Clinical Practice Guideline: Mechanical Ventilation in Adult Patients with Acute Respiratory Distress Syndrome". American Journal of Respiratory and Critical Care Medicine. 195 (9): 1253–1263. doi:10.1164/rccm.201703-0548ST. ISSN 1073-449X.
  14. ↑ Rhodes, Andrew; Evans, Laura E.; Alhazzani, Waleed; Levy, Mitchell M.; Antonelli, Massimo; Ferrer, Ricard; Kumar, Anand; Sevransky, Jonathan E.; Sprung, Charles L.; Nunnally, Mark E.; Rochwerg, Bram; Rubenfeld, Gordon D.; Angus, Derek C.; Annane, Djillali; Beale, Richard J.; Bellinghan, Geoffrey J.; Bernard, Gordon R.; Chiche, Jean-Daniel; Coopersmith, Craig; De Backer, Daniel P.; French, Craig J.; Fujishima, Seitaro; Gerlach, Herwig; Hidalgo, Jorge Luis; Hollenberg, Steven M.; Jones, Alan E.; Karnad, Dilip R.; Kleinpell, Ruth M.; Koh, Younsuk; Lisboa, Thiago Costa; Machado, Flavia R.; Marini, John J.; Marshall, John C.; Mazuski, John E.; McIntyre, Lauralyn A.; McLean, Anthony S.; Mehta, Sangeeta; Moreno, Rui P.; Myburgh, John; Navalesi, Paolo; Nishida, Osamu; Osborn, Tiffany M.; Perner, Anders; Plunkett, Colleen M.; Ranieri, Marco; Schorr, Christa A.; Seckel, Maureen A.; Seymour, Christopher W.; Shieh, Lisa; Shukri, Khalid A.; Simpson, Steven Q.; Singer, Mervyn; Thompson, B. Taylor; Townsend, Sean R.; Van der Poll, Thomas; Vincent, Jean-Louis; Wiersinga, W. Joost; Zimmerman, Janice L.; Dellinger, R. Phillip (2017). "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016". Intensive Care Medicine. 43 (3): 304–377. doi:10.1007/s00134-017-4683-6. ISSN 0342-4642.

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