TIMING DE TERAPIAS NO INVASIVAS IRA POR

COVID-19 ABRIL 2020

GRUPO MULTIDISCIPLINARIO ESPAÑOL DE EXPERTOS EN
TERAPIAS RESPIRATORIAS NO INVASIVAS
-VMNI-CR GRUPO-
DR. JOSÉ MIGUEL ALONSO ÍÑIGO MD, PHD
FED. ANESTESIOLOGÍA Y REANIMACIÓN. HOSPITAL UNIVERSITARIO Y POLITÉCNICO LA FE.
VALENCIA
DIRECTOR VMNI-CR GRUPO

DR. JOSÉ MANUEL CARRATALÁ PERALES MD

FED. URGENCIAS Y EMERGENCIAS. HOSPITAL GENERAL UNIVERSITARIO DE ALICANTE.
CO-DIRECTOR VMNI-CR GRUPO

DR. SALVADOR DÍAZ LOBATO

ESPECIALISTA EN NEUMOLOGÍA. DIRECTOR MÉDICO NIPPON GASES
CO-DIRECTOR VMNI-CR GRUPO

DR. DIEGO MORENO

FED. MEDICINA INTERNA. HOSPITAL UNIVERSITARIO DE MANISES. VALENCIA
FENOTIPOS NEUMONIA SARS-COV-2 EDITORIAL
Intensive Care Medicine

Un-edited accepted proof

COVID-19 pneumonia: different respiratory treatment for different

COVID-19 pneumonia, Type L phenotypes?
L. Gattinoni1, D. Chiumello2, P. Caironi3, M. Busana1, F. Romitti1, L. Brazzi4, L. Camporota5

Affiliations:
At the beginning, COVID-19 pneumonia presents with the following characteristics:
1
Department of Anesthesiology and Intensive Care, Medical University of Göttingen
4
Department of Anesthesia, Intensive Care and Emergency - 'Città della Salute e della Scienza’
• Low elastance: the nearly normal compliance indicates that the amount of gas in the lung is nearly normal
Hospital - Turin
5
Department of Adult Critical Care, Guy’s and St Thomas’ NHS Foundation Trust, Health Centre for
Human and Applied Physiological Sciences - London
• Low ventilation to perfusion (VA/Q) ratio: since the gas volume is nearly normal, hypoxemia may be best
explained by the loss of regulation of perfusion and by loss of hypoxic vasoconstriction. Accordingly, at this
stage, the pulmonary artery pressure, should be near normal.
Corresponding author:

Luciano Gattinoni

• Low lung weight: Only ground-glass densities are present on CTof Anesthesiology
Department scan, primarily located
and Intensive Care, subpleurally
Medical University of Göttingen, and

along the lung fissures. Consequently, lung weight is onlyRobert-Koch

moderately increased.
Straße 40, 37075, Göttingen, Germany

• Low lung recruitability: the amount of non-aerated tissue is very low, consequently the recruitability is low
Conflict of interests:

The authors have no conflict of interest to disclose

Gattinoni L. et al. COVID-19 (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2

FENOTIPOS NEUMONIA SARS-COV-2 EDITORIAL
Intensive Care Medicine

Un-edited accepted proof

COVID-19 pneumonia: different respiratory treatment for different

COVID-19 pneumonia, Type H phenotypes?
L. Gattinoni1, D. Chiumello2, P. Caironi3, M. Busana1, F. Romitti1, L. Brazzi4, L. Camporota5

The type H patient in more advanced stages Affiliations:

1
Department of Anesthesiology and Intensive Care, Medical University of Göttingen

•High elastance: The decrease of gas volume due to increased edema

Department accounts
4
of Anesthesia, forandthe
Intensive Care increased
Emergency lung
- 'Città della Salute e della Scienza’
Hospital - Turin
elastance. 5
Department of Adult Critical Care, Guy’s and St Thomas’ NHS Foundation Trust, Health Centre for
Human and Applied Physiological Sciences - London

•High right-to-left shunt: This is due to the fraction of cardiac output perfusing the non-aerated tissue which
develops in the dependent lung regions due to the increased edema and superimposed pressure.
Corresponding author:

•High lung weight: Quantitative analysis of the CT scan shows a remarkable increase in lung weight (> 1.5 kg),
Luciano Gattinoni

on the order of magnitude of severe ARDS Department of Anesthesiology and Intensive Care, Medical University of Göttingen,

Robert-Koch Straße 40, 37075, Göttingen, Germany

•High lung recruitability: The increased amount of non-aerated tissue is associated, as in severe ARDS, with
Conflict of interests:
increased recruitability
20-30%
The authors have no conflict of interest to disclose

Gattinoni L. et al. COVID-19 (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2

 FENOTIPOS
gure 1 NEUMONIA SARS-COV-2-TAC
COVID-19 pneumonia, Type L COVID-19 pneumonia, Type H

Gattinoni L. et al. COVID-19 (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2

 FENOTIPOS NEUMONIA
IRA PORSARS-C
EDITORIAL
OV-2-TAC
SARS-COV-2
Intensive Care Medicine

Un-edited accepted proof

dicine Figure 1 COVID-19 pneumonia, Type H

COVID-19 pneumonia, Type L
Un-edited accepted proof

Panel A: CT scan acquired during spontaneous breathing. The cumula

is shifted to the left (well aerated compartments), being the 0 to
aerated tissue virtually 0. Indeed, the total lung tissue weight was
aerated and the gas volume was 4228 ml. Patient receiving oxygen w
fraction of 0.8.

Panel B: CT acquired during mechanical ventilation at end-expiratory

cumulative distribution of the CT scan is shifted to the right (non-aera
compartments are greatly reduced. Indeed, the total lung tissue weig
not aerated and the gas volume was 1360 ml. The patient was ventil
7.8 ml/kg of tidal volume, respiratory rate of 20 breaths per minute,
Gattinoni L. et al. COVID-19 (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2
 FENOTIPOS NEUMONIA SARS-COV-2-TAC
Intensive Care Medicine
DITORIAL Un-edited accepted proof

igure 1 COVID-19 pneumonia, Type L COVID-19 pneumonia, Type H

Proceso evolutivo. Fenotipos mixtos

Panel A: CT scan acquired during spontaneous b

is shifted to the left (well aerated compartme

TIMING TERAPÉUTICO INTEGRADO

aerated tissue virtually 0. Indeed, the total lu
aerated and the gas volume was 4228 ml. Patien
fraction of 0.8.

Panel B: CT acquired during mechanical ventilat

cumulative distribution of the CT scan is shifted
compartments are greatly reduced. Indeed, the
Gattinoni L. et al. COVID-19 (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2
not aerated and the gas volume was 1360 ml. T
 FASES NEUMONÍA POR SARS-COV-2 Intensive Care Medicine
EDITORIAL Un-edited accepted proof

Figure 1

Estadio I Infección Estadio II Fase Estadio III Fase

LDH
Gravedad de Enfermedad

Precoz Pulmonar Hiperinflamatoria

Intensive Care Medicine
EDITORIAL Un-edited accepted proof

Ferrit
Figure 1

IL-6
Di-D
Fase de Respuesta Viral Fase de (Hiper) Respuesta Inflamatoria
Panel A: CT scan acquired during spontaneous breathing. The cumulative distribution of the CT number
is shifted to the left (well aerated compartments), being the 0 to -100 HU compartment, the non-
aerated tissue virtually 0. Indeed, the total lung tissue weight was 1108 g, 7.8% of which was not
aerated and the gas volume was 4228 ml. Patient receiving oxygen with Venturi mask, inspired oxygen
fraction of 0.8.

Panel B: CT acquired during mechanical ventilation at end-expiratory pressure at 5 cmH2O of PEEP. The
cumulative distribution of the CT scan is shifted to the right (non-aerated compartments) while the left
compartments are greatly reduced. Indeed, the total lung tissue weight was 2744 g, 54% of which was
not aerated and the gas volume was 1360 ml. The patient was ventilated in Volume Controlled mode,
7.8 ml/kg of tidal volume, respiratory rate of 20 breaths per minute, inspired oxygen fraction of 0.7

Linfos
6
Gattinoni L. et al. COVID-19 pneumonia: different respiratory treatment for different
phenotypes? (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2
Panel A: CT scan acquired during spontaneous breathing. The cumulative distribution of the CT number
is shifted to the left (well aerated compartments), being the 0 to -100 HU compartment, the non-
aerated tissue virtually 0. Indeed, the total lung tissue weight was 1108 g, 7.8% of which was not

Fase de Respuesta Inmune (Claudicación) PLAQ

aerated and the gas volume was 4228 ml. Patient receiving oxygen with Venturi mask, inspired oxygen
fraction of 0.8.

Panel B: CT acquired during mechanical ventilation at end-expiratory pressure at 5 cmH2O of PEEP. The
cumulative distribution of the CT scan is shifted to the right (non-aerated compartments) while the left
compartments are greatly reduced. Indeed, the total lung tissue weight was 2744 g, 54% of which was
not aerated and the gas volume was 1360 ml. The patient was ventilated in Volume Controlled mode,
7.8 ml/kg of tidal volume, respiratory rate of 20 breaths per minute, inspired oxygen fraction of 0.7

Curso Evolutivo
Gattinoni L. et al. COVID-19 pneumonia: different respiratory treatment for different
phenotypes? (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2
SEMIOLOGÍA

Sintomatolología Constucional SDRA, SHF reactivo, Sepis, SIRS, Shock, Fallo

Disnea, Hipoxemia
Fiebre, tos seca, diarrea, cefalea, alteraciones Cardiaco
PO2/FiO2<300
gusto y olfato

Infiltrados pulmonares uni-bilaterales. Elevación de marcadores inflamatorios y de

Linfocitosis o inicio de Linfopenia, aumento de
LABORATORIO

Elevación de transaminasas, PCT normal o disfunción endotelial y coagulación (LDH,

PCR, tiempo de protrombina, Dímeros-D y LDH Ferritina, PCR, IL-6, D-Dímeros)
baja, linfopenia creciente
Aumento de Troponina y Pro-BNP

ALERTA VENTILATORIA
MANEJO TNI IRA POR SARS-COV-2
TIMING TNI IRA SARS-COV-2
Inicio Precoz de TAF
50-60 l/min
FiO2 0,8-0,9

Inicio Precoz de VMNI

EDITORIAL
Intensive Care Medicine

Un-edited accepted proof

Protección Pulmonar
Figure 1 FiO2 0,8-0,9

Intensive Care Medicine

EDITORIAL Un-edited accepted proof

Figure 1

Estrategia de Rotación de Terapias de

Panel A: CT scan acquired during spontaneous breathing. The cumulative distribution of the CT number
is shifted to the left (well aerated compartments), being the 0 to -100 HU compartment, the non-
aerated tissue virtually 0. Indeed, the total lung tissue weight was 1108 g, 7.8% of which was not
Protección pulmonar
Valorar curso clínico y tolerancia
aerated and the gas volume was 4228 ml. Patient receiving oxygen with Venturi mask, inspired oxygen
fraction of 0.8.

Panel B: CT acquired during mechanical ventilation at end-expiratory pressure at 5 cmH2O of PEEP. The
Preferible CPAP/TAF
ALERTA cumulative distribution of the CT scan is shifted to the right (non-aerated compartments) while the left
compartments are greatly reduced. Indeed, the total lung tissue weight was 2744 g, 54% of which was
not aerated and the gas volume was 1360 ml. The patient was ventilated in Volume Controlled mode,

VENTILATORIA
7.8 ml/kg of tidal volume, respiratory rate of 20 breaths per minute, inspired oxygen fraction of 0.7

6
Gattinoni L. et al. COVID-19 pneumonia: different respiratory treatment for different
Panel A: CT scan acquired during spontaneous breathing. The cumulative distribution of the CT number
phenotypes? (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2
is shifted to the left (well aerated compartments), being the 0 to -100 HU compartment, the non-
aerated tissue virtually 0. Indeed, the total lung tissue weight was 1108 g, 7.8% of which was not
aerated and the gas volume was 4228 ml. Patient receiving oxygen with Venturi mask, inspired oxygen
fraction of 0.8.

Panel B: CT acquired during mechanical ventilation at end-expiratory pressure at 5 cmH2O of PEEP. The
cumulative distribution of the CT scan is shifted to the right (non-aerated compartments) while the left
compartments are greatly reduced. Indeed, the total lung tissue weight was 2744 g, 54% of which was
MANEJO VENTILATORIO IRA POR SARS-COV-2
Intensive Care Medicine

EDITORIAL Un-edited accepted proof

COVID-19
Figure 1 pneumonia, Type L

Inicio Precoz de TAF

50-60 l/min
FiO2 0,8-0,9

Valorar Drive Respiratorio

Pes swing

Panel A: CT scan acquired during spontaneous breathing. The cumulative distribution of the CT number
Estrategia
is shifted to the leftde Rotación
(well aerated compartments),de being the 0 to -100 HU compartment, the non-
aerated tissue virtually 0. Indeed, the total lung tissue weight was 1108 g, 7.8% of which was not
Terapias de Protección pulmonar
aerated and the gas volume was 4228 ml. Patient receiving oxygen with Venturi mask, inspired oxygen
fraction of 0.8.

Valorar curso clínico y tolerancia

Preferible CPAPof the(8-14 cmto theH2O)
Panel B: CT acquired during mechanical ventilation at end-expiratory pressure at 5 cmH O of PEEP. The
cumulative distribution CT scan is shifted
2
right (non-aerated compartments) while the left
compartments are greatly reduced. Indeed, the total lung tissue weight was 2744 g, 54% of which was
not aerated and the gas volume was 1360 ml. The patient was ventilated in Volume Controlled mode,
7.8 ml/kg of tidal volume, respiratory rate of 20 breaths per minute, inspired oxygen fraction of 0.7

6
Gattinoni L. et al. COVID-19 pneumonia: different respiratory treatment for different
phenotypes? (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2 Gattinoni L. et al. COVID-19 (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2
MANEJO VENTILATORIO IRA POR SARS-COV-2 Intensive Care Medicine
EDITORIAL Un-edited accepted proof

COVID-19 pneumonia, Type L

Figure 1
1.Volumes greater than 6 ml/kg (up to 8-9 ml/kg)

2.Prone positioning should be used only as a rescue

maneuver, which is based on improved stress and strain
redistribution.

Inicio Precoz de TAF 3.PEEP should be reduced to 8-10 cmH2O, given that the
50-60 l/min recruitability is low and the risk of hemodynamic failure
FiO2 0,8-0,9 increases at higher levels.
Valorar Drive Respiratorio
Pes swing

Estrategia de Rotación de
Terapias
Panel de during
A: CT scan acquired Protección
spontaneous breathing. The cumulative distribution of the CT number
is shifted to the left (well aerated compartments), being the 0 to -100 HU compartment, the non-
aerated tissuepulmonar
virtually 0. Indeed, the total lung tissue weight was 1108 g, 7.8% of which was not Protocolos Manejo
aerated and the gas volume was 4228 ml. Patient receiving oxygen with Venturi mask, inspired oxygen
Valorar
fraction of 0.8. curso clínico y Ventilación Invasiva (VMI)
tolerancia
Panel B: CT acquired during mechanical ventilation at end-expiratory pressure at 5 cmH O of PEEP. The
Preferible CPAP
2
cumulative distribution of the CT scan is shifted to the right (non-aerated compartments) while the left
compartments are greatly reduced. Indeed, the total lung tissue weight was 2744 g, 54% of which was
not aerated and the gas volume was 1360 ml. The patient was ventilated in Volume Controlled mode,
7.8 ml/kg of tidal volume, respiratory rate of 20 breaths per minute, inspired oxygen fraction of 0.7 Gattinoni L. et al. COVID-19 (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2
MANEJO VENTILATORIO IRA POR SARS-COV-2
COVID-19 pneumonia, Type H

Type H patients, should be treated

as severe ARDS, including higher
PEEP, if compatible with
hemodynamics, prone positioning
and extracorporeal support.

Gattinoni L. et al. COVID-19 (2020) Intensive Care Medicine; DOI: 10.1007/s00134-020-06033-2

TRATAMIENTO SEGÚN NIVEL DE GRAVEDAD Y EVOLUCIÓN
Timeline /Timing (días)
Infección LEVE vías respiratorias
altas con Rx Tórax NORMAL y > 65
años sin comorbilidad, o cualquier
edad con comorbilidades y/o
inmunosupresión, y criterios de
INGRESO HOSPITALARIO
Evolución de:
• <7 días: Lopinavir/ritonavir
• >7 días: Hidroxicloroquina o
cloroquina ± azitromicina
S. DE URGENCIAS
HBPM SC profiláctica
Infección sin requerir
hospitalización:
• Asintomático
• Oligosintomático leve
3-5
Neumonía no grave
CURB 65 ≤ 1 e
Infiltrado < 1 lóbulo
SpO2 > 92% y/o FR < 24
Linfocitos ≥ 1000 cels/µl
DD < 1000, LDH < 300, IL-6 < 40
INGRESO EN PLANTA
Hidroxicloroquina o Cloroquina
± Azitromicina VO
Duración 5 días, si mejoría
Valoración de tto. Inmunomodulador: Corticoides; Baricitinib en hipoxemia leve y Tocilizumab en moderada grave
5-7 7-10 Ventana oportunidad >14 días
Neumonía grave con factores de riesgo de Neumonía muy grave
progresión Infiltrado multilobar o Bilateral y/o
CURB 65 > 1 e Infiltrado multilobar o Bilateral, PaO2/FiO2 <300y/o FR >30, Fallo multiorgánico,
o SpO2 ≤ 92% y/o FR >24 o sepsis o shock séptico o
Linfocitos < 1000 cels/µl TAS ≤ 90 o Linfocitos < 500 cels/µl
DD > 1000, LDH > 300, IL-6 > 40 DD > 2000, LDH > 350, IL-6 > 100
INGRESO EN PLANTA Y MONITORIZACIÓN INGRESO EN UCI/REA/UCRI
Hidroxicloroquina o cloroquina ± Lopinavir/rtv solución? + Hidroxicloroquina +
Azitromicina (VO, IV) Azitromicina (VO, IV)
Si VMNI: Valorar BARICITINIB - TOCILIZUMAB
Si VMI: solicitar REMDESIVIR (uso compasivo,
solo disponible para embarazadas y menores de
Duración 5 días, si mejoría
18 años)
¡¡Si no mejoría al 3º-5º día o inicio de progresión!!

Considerar Inmunoterapia: Igs IV en planta (o suero

TTO SINTOMÁTICO y ALERTA VENTILATORIA hiperinmune de convalescentes, bajo EC en UCI)
OBSERVACIÓN
Pautar HBPM SC profiláctica. Ajuste por peso à Considerar anticoagulación
ATENCIÓN PRIMARIA
Usar Corticoides si progresión clínica
Considerar HBPM SC profiláctica PROTOCOLO TNI
inflamatoria, SDRA, encefalitis, broncoespasmo
PRECAUCIONES EN EL TRATAMIENTO POR SARS-COV-2
• En el momento actual, NO existe ningún tratamiento farmacológico con suficiente
evidencia como para recomendar su uso sistemático.

• POR TANTO, el tratamiento debe individualizarse y reajustarse según la FASE de la

infección y la EVOLUCIÓN CLÍNICA.

• “Many professional organizations have developed interim guidelines for the

management and prevention of Covid-19. Guidelines [..] highlight the fact that there
are no proven therapies for Covid-19 and that randomized trials are critical.”

• Por otro lado, el uso precoz de HBPM y al alta hospitalaria podría mejorar las
complicaciones trombóticas asociadas al COVID.

Mild or Moderate Covid-19. N Engl J Med. 2020 Apr 24. doi: 10.1056/NEJMcp2009249
TNI IRA POR SARS-COV-2