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Syndrome de Détresse Respiratoire Aiguë
en contexte de SARS-CoV2
Dr GODET Thomas
Dr AUDARD Jules
Dr BLONDONNET Raïko
PIOCHE Pierre-Antoine
Pôle Médecine Péri-Opératoire
24 mars 2020
DiagnosticIntroduction SARS-CoV2Traitement
SDRA Léger Modéré Sévère Tous
Mortalité à J28 29,6% 35,2% 40,9% 34,8%
Epidemiology, Patterns of Care, and mortality for
patients with ARDS in ICU in 50 countries
Bellani et al. JAMA 2016
DiagnosticIntroduction SARS-CoV2Traitement
Le SDRA c’est quoi ?
Atteinte directe
- Pneumopathie infectieuse (bactérienne/virale)
- Inhalation de liquide gastrique
Atteinte indirecte
- Choc septique
- Polytraumatisé
DiagnosticIntroduction SARS-CoV2Traitement
Le SDRA c’est quoi ?
Acute Respiratory Distress Syndrome
Thompson et al. NEJM 2017
Epithélium bronchique
Pneumocyte type I
Surfactant
Capillaire
Bactérie, virus, champignon,
trauma, liquide gastrique
Rupture endothéliale
Coagulation intravasculaire
Inondation interstitielle
Rupture de la membrane
basale
Œdème alvéolaire
Inactivation du surfactant
et lésion épithéliale
SainExsudatif
Macrophage
alvéolaire
Réponse
inflammatoire
L-T
NETs
ROS
Elastase
…Neutro
Pneumocyte type II
DiagnosticIntroduction SARS-CoV2Traitement
Le SDRA c’est quoi ?
Acute Respiratory Distress Syndrome
Thompson et al. NEJM 2017
DiagnosticIntroduction SARS-CoV2Traitement
Comment le diagnostiquer ?
Comment le diagnostiquer ?
Acute Respiratory Distress Syndrome
The Berlin Definition
Ferguson et al. JAMA 2012
Léger Modéré Sévère
Temps Début < 1 semaine, contexte clinique compatible
Hypoxémie
x = PaO2/FiO2
(mmHg)
200 < x ≤ 300 100 < x ≤ 200 ≤ 100
Chez un patient ventilé avec PEP ≥ 5cmH2O
Origine de l’œdème
Défaillance respiratoire non expliquée entièrement par une
insuffisance cardiaque ou une surcharge volémique
Anomalies
radiologiques
Opacités bilatérales non expliquées par des épanchements,
atélectasies ou nodules
Définition
DiagnosticIntroduction SARS-CoV2Traitement
DiagnosticIntroduction SARS-CoV2Traitement
Quels moyens thérapeutiques ?
DiagnosticIntroduction SARS-CoV2Traitement
Quels moyens thérapeutiques ?
TRAITEMENT ETIOLOGIQUE
Quid du COVID 19 ?
TRAITEMENT SYMPTOMATIQUE
Oxygéner le sang
Epurer le CO2
Protéger le poumon
Oxygénation artérielle
DiagnosticIntroduction SARS-CoV2Traitement
Epuration du CO2
PaCO2
PaO2
Ventilation à petits volumes Ventilation à hauts volumes
Atélectasies Hétérogénéité Fuites d’air
Conséquences structurelles
Trasnformations
épithéliales
Dysfonction du
surfactant
Membranes
hyalines
Perte de l’épithélium bronchique
Œdème
pulmonaire
Hyperperméabilité
Alvéolo-capillaire
Alvéole
Alvéole
Atélectasies
Hyperdistension
Alvéole
Prolifération des
fibroblastes
DiagnosticIntroduction SARS-CoV2Traitement
Ventilator-Induced Lung Injury
Slutsky et al. NEJM 2013
DiagnosticIntroduction SARS-CoV2Traitement
Ventilator-Induced Lung Injury
Slutsky et al. NEJM 2013
Ne pas être délétère !
Zone non aérée
Zone pauvrement aérée
Zone normalement aérée
DiagnosticIntroduction SARS-CoV2Traitement
300 200 100250 150 50 PaO2/FiO2
Faible Volume Courant (6 ml.kg-1 de PIT)
SDRA léger SDRA modéré SDRA sévère
PEP élevée
Décubitus Ventral
Curarisation
Manœuvre de Recrutement Alvéolaire
ECMO
PEP ≥ 5 cmH2O
Thérapeutiques selon la sévérité
Recommandations
formelles
A discuter
DiagnosticIntroduction SARS-CoV2Traitement
PRESSION
DEBIT
Pression de crête = Pmax
Pression de plateau = Pplat
Temps de pause télé-inspiratoire
Mode en volume - VVC
VTi
Ouverture valve insp
Fermeture valve expi
Fermeture valve insp
Ouverture valve expi
Tinspiratoire Texpiratoire
Prone positionning in ARDS
Guérin et al. NEJM 2013
DiagnosticIntroduction SARS-CoV2Traitement
Lien Vidéo :
https://drive.google.com/open?id=1bByZrZmIK_SbnmLvzHqn1t
sGD4a0woQQ
Introduction SARS-CoV2Traitement
Epidémiologie
Diagnostic
Asymptomatiques
Insuffisance
respiratoire
19%
Admission en réaBesoin en O2
Ventilation
mécanique
SDRA
14% 5%
67%
Hommes
> 60 ans
Comorbidités
(Diabète, Cancer, ID)
IOT + pathologies cardiovasculaires, Insuffisance Respiratoire chronique,
HTA, Diabète, Cancer
1-2%
Wu Z et al. JAMA, 2020
Introduction SARS-CoV2Traitement
Gestion du risque de contamination
Diagnostic
AIR DOIT SORTIR
Protection du patient
(immunodéprimés)
AIR DOIT RENTRER
Protection de l’environnement
(contagion)
SAS
Pression
négative
Réa MIR
Réa Adultes Estaing
Introduction SARS-CoV2Traitement
Gestion du risque de contamination
Diagnostic
Contamination des soignants ++
10%
Limiter le nombre de soignants
FFP2 pour les procédures générant une aérosolisation*
Chambre en pression négative
(si dispo, 12 changements volume d’air/h 160L/s/patient)
FFP 2
Pièce Faciale Filtrante
Pourcentage de filtration d'aérosols
(% minimum)
Pourcentage de fuite vers l'intérieur
(% maximum)
FFP1 80 22
FFP2 94 8
FFP3
99 (EN 149-FFP3)
99,95 (EN 143-P3)
2
*Procédures aérosolisantes
Intubation
Bronchoscopie
Aspi en système ouvert
Ventilation manuelle (BAVU)
Déconnection
Trachéotomie
Mise en Décubitus ventral
+/- ONHD et VNI
Introduction SARS-CoV2Traitement
Gestion du risque de contamination
Diagnostic
POUR TOUTES LES AUTRES PROCEDURES
Introduction SARS-CoV2Traitement
Gestion du risque de contamination
Diagnostic
INTUBATION ORO-TRACHEALE
Vidéolaryngoscope si disponible
par opérateur expérimenté
Lien vidéo : https://drive.google.com/open?id=1NM9Q-f_DR0fyxrOrNvIDUH9rw0_ntH3B
Introduction SARS-CoV2Traitement
Gestion du risque de contamination
Diagnostic
MONTAGE DU CIRCUIT DU RESPIRATEUR
Filtre hydrophobe
à haute capacité
de filtration
Filtre HEPA (machine) à remplacer
toutes les 48h
Filtres/Tuyaux à remplacer après
chaque COVID19 +
(anesthésie)
Filtre HME (patient) à remplacer
toutes les 48h ou si souillures
Introduction SARS-CoV2Traitement
Gestion du risque de contamination
Diagnostic
PRISE EN CHARGE PARAMEDICALE
Lien vidéo : https://drive.google.com/open?id=1keADAc3me6fRajBaoY1Bpuj49LO5bIlT
Mettre sur pause le ventilateur
AVANT toute déconnection
Garder le filtre connecté à la sonde
d’intubation (si possible)
Clamper la sonde d’intubation
(si possible)
Introduction SARS-CoV2Traitement
Prise en charge respiratoire
Diagnostic
OXYGENOTHERAPIE
Si SpO2 < 92%
sans signe de détresse respiratoire
O2Quels dispositifs ?
Sonde
Nasale
0,5 à 6 l/min
Canule
nasale
Masque facial
simple
Max 10 l/min
Masque facial
avec réservoir
Max 15 l/min
OHD
35 à 60 l/min
Intubation
trachéale
VNI ou CPAP
O2Quels dispositifs ?
Sonde
Nasale
0,5 à 6 l/min
Canule
nasale
Masque facial
simple
Max 10 l/min
Masque facial
avec réservoir
Max 15 l/min
OHD
35 à 60 l/min
Intubation
trachéale
VNI ou CPAP
O2Quels dispositifs ?
nde
sale
0,5 à 6 l/min
Canule
nasale
Masque facial
simple
Max 10 l/min
Masque facial
avec réservoir
Max 15 l/min
OHD
35 à 60 l/min
Intubation
trachéale
VNI ou CPAP
acial
rvoir
min
OHD
35 à 60 l/min
Intubation
trachéale
VNI ou CPAP
Introduction SARS-CoV2Traitement
Prise en charge respiratoire – Recos 1/2
Diagnostic
OXYGENATION NASALE A HAUT DEBIT +++
Attention, différent des recos françaises
EVITER LA VNI
Surmortalité, sauf si OHND indisponible
1
2
SURVEILLANCE CLINIQUE +++ MONITORAGE
Fréquence respi, balancement thoraco-
abdo, signes de lutte, hypovigilance
3
NE PAS RETARDER L’INTUBATION
4
Introduction SARS-CoV2TraitementDiagnostic
24
oxygen use, and the potential to reduce equity if oxygen resources are depleted; the panel issued a
strong recommendation against using oxygen to target SPO2>96%, and a strong recommendation to
avoid lower SPO2<90%. Therefore, a reasonable SPO2 range for patients receiving oxygen 92% to
96%.
Recommendation:
25. For adults with COVID-19 infection and acute hypoxemic respiratory failure, we suggest
using HFNC over conventional oxygen therapy (weak recommendation, low quality evidence)
Rationale:
There is no direct evidence on patients with COVID-19, therefore, the panel used indirect evidence
from the critically ill population to inform this recommendation. In an RCT comparing HFNC to
conventional oxygen therapy for patients with acute hypoxic respiratory failure, HFNC resulted in
reduced 90-day mortality (OR 0.42; 95% CI 0.21 to 0.85) but did not reduce the risk of intubation
[70]. A systematic review and meta-analysis of 9 RCTs (2,093 patients) showed that HFNC reduces
intubation compared to conventional oxygen (RR 0.85; 95% CI 0.74 to 0.99) but did not affect risk
of death or ICU length of stay.[71-73] Even though evidence for mortality and length of stay is not
endotracheal intubation, especially for nurses (OR 6.6, 95% Cl 2.3 to 18.9) [28, 74, 75]. While this is
based mostly on retrospective observational studies, HFNC does not seem to confer an increased
risk of transmission of disease. In studies evaluating bacterial environmental contamination, HFNC
resulted in similar contamination risk as conventional oxygen [76]. In SARS, health care workers
exposed to HFNC were not at increased risk of developing disease [74]. Finally, patients may find
HFNC more comfortable or at least as comfortable as conventional oxygen therapy [70, 73].
Although some authors advised avoiding the use of HFNC in patients with COVID-19 due to fear
of disease transmission, studies supporting this advice are lacking [77].
Recommendation:
26. For adults with COVID-19 and acute hypoxemic respiratory failure, we suggest using
HFNC over NIPPV (weak recommendation, low quality evidence).
Rationale:
In adults with COVID-19 and acute respiratory failure, we suggest the use of HFNC over NIPPV.
In an RCT comparing HFNC to NIPPV for patients with acute hypoxic respiratory failure, HFNC
resulted in reduced mortality at 90 days (HR 2.50; 95% CI 1.31 to 4.78) but did not significantly
affect the need for intubation (50% failure rate in NIPPV vs 47% in conventional oxygen and 40%
in HFNC; p=0.18) [70]. Other meta-analysis comparing HFNC to NIPPV have shown HFNC to
decrease the need for intubation of patients compared to NIPPV without significantly decreasing
mortality or ICU length of stay [71]. Additionally, patients may find HFNC more comfortable than
NIPPV [70]. Given the evidence for decreased risk of intubation for HFNC compared to NIPPV in
acute hypoxemic respiratory failure and studies suggesting that NIPPV may confer greater risk for
nosocomial infection of healthcare providers for infected patients, we suggest HFNC over NIPPV.
However, any patients receiving HFNC or NIPPV should be monitored closely and cared for in a
setting where intubation can be facilitated in the event of decompensation as failure rate may be high
and emergent intubation in an uncontrolled setting may increase risk of nosocomial infection of
Recommendations:
27. For adults with COVID-19 and acute hypoxemic respiratory failure, if HFNC is not available
and no emergent indication for endotracheal intubation; we suggest a trial of NIPPV with close
monitoring and short interval assessment for worsening respiratory failure (weak
recommendation, very low quality evidence).
28. We were not able to make a recommendation regarding the use of helmet NIPPV compared
to mask NIPPV, it is an option, but we are not certain about its safety or efficacy in COVID-19
29. For adults with COVID-19 infection receiving NIPPV or HFNC, we recommend close
monitoring for worsening of respiratory status and early intubation in a controlled setting if
worsening occurs (best practice statement).
Rationale:
Recommendations:
27. For adults with COVID-19 and acute hypoxemic respiratory failure, if HFNC is not available
and no emergent indication for endotracheal intubation; we suggest a trial of NIPPV with close
monitoring and short interval assessment for worsening respiratory failure (weak
recommendation, very low quality evidence).
28. We were not able to make a recommendation regarding the use of helmet NIPPV compared
to mask NIPPV, it is an option, but we are not certain about its safety or efficacy in COVID-19
29. For adults with COVID-19 infection receiving NIPPV or HFNC, we recommend close
monitoring for worsening of respiratory status and early intubation in a controlled setting if
worsening occurs (best practice statement).
Rationale:
Recommendations:
27. For adults with COVID-19 and acute hypoxemic respiratory failure, if HFNC is not available
and no emergent indication for endotracheal intubation; we suggest a trial of NIPPV with close
monitoring and short interval assessment for worsening respiratory failure (weak
recommendation, very low quality evidence).
28. We were not able to make a recommendation regarding the use of helmet NIPPV compared
to mask NIPPV, it is an option, but we are not certain about its safety or efficacy in COVID-19
29. For adults with COVID-19 infection receiving NIPPV or HFNC, we recommend close
monitoring for worsening of respiratory status and early intubation in a controlled setting if
worsening occurs (best practice statement).
Rationale:
Prise en charge respiratoire – Recos 1/2
Surviving Sepsis Campaign:
Guidelines on the Management
of Critically Ill Adults with
Coronavirus Disease 2019
(COVID-19)
Alhazzani et al. ICM, 2020
Introduction SARS-CoV2TraitementDiagnostic
STRATEGIE RESTRICTIVE DE REMPLISSAGE VASCULAIRE
SEANCES DE DECUBITUS VENTRAL DE 12 A 16h
Pour SDRA modéré à sévère
5
6
CURARISATION (NON DEPOLARISANTS) intermittente ou continue pour 48H
Pour SDRA modéré à sévère, pour faciliter
la protection pulmonaire ou en cas de
désynchronisation
7
Prise en charge respiratoire – Recos 2/2
MANŒUVRES DE RECRUTEMENT
8
Introduction SARS-CoV2TraitementDiagnostic
Prise en charge respiratoire – Recos 2/2
MANŒUVRES DE RECRUTEMENT
8
PRESSION
5
MODE VSAI
Augmentation du
temps d’apnée +++ PEP = 30-40cmH2O
10 – 30s
Introduction SARS-CoV2TraitementDiagnosticClinicians can use the ARDS Network protocol strategies to determine the optimal PEEP level,
other strategies are available such as decremental PEEP strategy, esophageal balloon, and electrical
impedance tomography, however, the effect of using these techniques on clinical outcomes is
unknown.
Recommendation:
33. For mechanically ventilated adults with COVID-19 and ARDS, we suggest using a conservative
fluid strategy over a liberal fluid strategy (weak recommendation, low quality evidence).
Rationale:
The optimal fluid strategy in COVID-19 is not known, however, it is plausible to assume that these
patients will respond to fluid similar to other ARDS patients. Based on the limited data on COVID-
19, cardiac failure has been reported to be the cause of death in 40% of COVID-19 deaths, alone or
with respiratory failure [45]. Another study showed that 44% of COVID-19 patients had
arrhythmia[42]. The data suggest myocardial injury in some patients with COVID-19. In ARDS,
few RCTs have been published that compare conservative or de-resuscitative and liberal fluid
strategies. A recent systematic review included 5 RCTs enrolling 1,206 patients with ARDS, risk of
death was similar in both groups, 28 % in the conservative fluid strategy group and 31.1% in the
liberal strategy group (RR 0.91, 95% CI 0.77 to 1.07)[51]. This study included RCTs on critically ill
patients with or without ARDS, they found that conservative fluid strategy increased ventilator free
days ventilator free days (MD 1.82 days; 95 % CI 0.53 to 3.10 days) and reduced ICU length of stay
(MD - 1.88 days, 95 % CI -0.12 to -3.64 days), compared to a liberal fluid strategy. There was no
difference in harm, including renal failure between the two groups. The landmark trial on ARDS
patients (FACTT) found a significant reduction in the duration of mechanical ventilation with
conservative fluid strategy [108]. Furthermore, majority of patients with COVID-19 in the ICU are
elderly, and may develop myocardial dysfunction which could limit their ability to handle large fluid
34. For mechanically ventilated adults with COVID-19 and moderate to severe ARDS, we
suggest prone ventilation for 12 to 16 hours, over no prone ventilation (weak recommendation,
low quality evidence).
Rationale:
The radiological findings of COVID-19 has been described in 81 patients, the radiological features
seemed to progress over the course of 1 to 2 weeks of symptom onset from predominant ground
glass opacities to a mixed pattern with consolidation mostly at the lung bases [109], which makes
prone ventilation an attractive option. Prone ventilation theoretically makes ventilation more
homogeneous by decreasing ventral alveolar distention and dorsal alveolar collapse [110]. Ultimately,
reducing the difference between the dorsal and ventral transpulmonary pressures. In addition, prone
ventilation reduces lung compression [111] and improve perfusion [112].
A recent study that described the clinical course of COVID-19 in the ICU showed the prone
ventilation was used in 11.5% (6 out of 52 patients)[41], however, there are no studies to describe
the clinical course of patients with COVID-19 who were ventilated in the prone position.
A recent systematic review and meta-analysis of 9 RCTs (2,129 patients) showed that prone
ventilation for at least 12 hours in patients with moderate to severe ARDS reduce mortality (5 RCTs;
A protocol for proning should be used at each institution, based on the available resources and level
of training. If prone ventilation is used, healthcare workers should be aware of complications such as
pressure sores, vascular line and endotracheal tube displacement, facial edema, transient
hemodynamic instability, corneal abrasions, brachial plexus injury, hemodialysis vascular access flow
issues.
In addition, clinicians should be familiar with absolute contraindications for prone ventilation such
as unstable spine, open abdomen or open chest (i.e. surgery or trauma). Enteral nutrition via
nasogastric or nasoduodenal tube can be continued during proning [117, 118].
Recommendations:
35. For mechanically ventilated adults with COVID-19 infection and moderate to severe ARDS:
35.1. We suggest using as needed intermittent boluses of neuromuscular blocking
agents (NMBA), over a continuous NMBA infusion, to facilitate protective lung
ventilation (weak recommendation, low quality evidence).
35.2. In case of persistent ventilator dyssynchrony, requirement of ongoing deep
sedation, prone ventilation, or persistently high plateau pressures; we suggest
using a continuous NMBA infusion for up to 48 hours (weak recommendation,
low quality evidence).
Rationale:
Several professional societies issued recommendations on the use of NMBAs in ARDS [99, 119-
Prise en charge respiratoire – Recos 2/2
38. For mechanically ventilated adults with COVID-19 and hypoxemia
despite optimizing ventilation, we suggest using recruitment maneuvers,
over not using recruitment maneuvers (weak recommendation, low
quality evidence).
39. If recruitment maneuvers are used, we recommend against using
staircase (incremental PEEP) recruitment maneuvers (strong
recommendation, moderate quality evidence).
Surviving Sepsis Campaign:
Guidelines on the Management
of Critically Ill Adults with
Coronavirus Disease 2019
(COVID-19)
Alhazzani et al. ICM, 2020
Introduction SARS-CoV2Traitement
Monitorage et objectifs de soins – Recos 1/2
Diagnostic
OBJECTIF SpO2 = 92-96% max
Surmortalité dans l’hyperoxémie prolongée
GAZOMETRIE 1 fois par jour (à 8h)
2 possibles si défaillance hémodynamique
1
2
ECONOMIE DES RESSOURCES en O2 – CIRCUIT FERME EN ANESTHESIE
3
Another study reported on 52 critically ill COVID-19 patients, 67% of patients had ARDS, 33
63·5% of patients received high-flow nasal cannula (HFNC), 56% invasive mechanical ventilation
and 42% received NIPPV [41].
Risk factors for respiratory failure
Risk factors associated with respiratory failure requiring mechanical ventilation were not clearly
described in published reports, although from the limited available data, risk factors associated with
a critical illness/ICU admission included older age (>60 years), male gender, presence of underlying
comorbidities such as diabetes, malignancy, and immunocompromised state [1, 12, 41, 42].
The CDC reported an overall case-fatality rate (CFR) of 2.3%, with a CFR of 14.8% in patients 80
years or older. In critically ill patients, the CFR was 49.0% and higher than 50% in those who
received invasive mechanical ventilation. The presence of pre-existing comorbid condition such as
cardiovascular disease, diabetes, chronic respiratory disease, hypertension, and cancer were
associated with higher risk of death [12].
Recommendation:
23. For adults with COVID-19, we suggest starting supplemental oxygen if the peripheral oxygen
saturation (SPO2) is < 92%, and recommend starting supplemental oxygen if SPO2 is < 90%
24. For adults with COVID-19 and acute hypoxemic respiratory failure on oxygen; we
recommend that SPO2 be maintained no higher than 96% (strong recommendation, moderate
quality evidence).
Rationale:
Surviving Sepsis Campaign:
Guidelines on the Management
of Critically Ill Adults with
Coronavirus Disease 2019
(COVID-19)
Alhazzani et al. ICM, 2020
Introduction SARS-CoV2TraitementDiagnostic
OBJECTIF EtCO2 (30-35 mmHg) à corréler avec PaCO2 +++
Intérêt ++ de la capnographie en continu
SURVEILLANCE CLINIQUE +++
4
6
Monitorage et objectifs de soins – Recos 2/2
Pplat statique/4h pour OBJECTIF < 30 cmH2O5
Mesure par pause inspiratoire > 3s
Introduction SARS-CoV2TraitementDiagnostic
Monitorage et objectifs de soins – Recos 2/2
PRESSION
DEBIT
Pression de plateau = Pplat
Temps de pause télé-inspiratoire
3s
Pplat statique/4h pour OBJECTIF < 30 cmH2O5
Introduction SARS-CoV2Traitement
Traitement étiologique
Diagnostic
PLAQUENIL
Hydroxychloroquine
(antipaludéen, PR, lupus)
Diminution du pH lysosomial et de la
réplication du virus
200mg x 3/j pendant 10j
+ Azithromycine 500mg J1 puis
250mg/j J2-J5
Intensive Care Medicine
GUIDELINES Un-edited accepted proof*
1.12 to 5.72) [147]. The only direct evidence comes from a retrospective cohort study of 201 patients with
COVID-19 pneumonia. This study showed an association between corticosteroid use and lower mortality in
patients with COVID-19 and ARDS (HR 0.38, 95%CI 0.20 to 0.72). However, the estimate was not adjusted
for confounding factors [148].
The effect of corticosteroids in COVID-19 patients with sepsis or septic shock may be different. Recent
systematic reviews and meta-analyses of RCTs in sepsis showed small improvements in mortality and faster
resolution of shock with corticosteroid use, compared with not using corticosteroids [63, 149, 150] (see the
previous section on hemodynamic support).
It is widely recognized that corticosteroids have a range of adverse effects. In viral pneumonia in the ICU,
several studies showed increase in viral shedding with corticosteroid use [151-153], potentially indicating viral
replication, but the clinical implication of increased viral shedding is uncertain.
Considering the above, the panel issued a suggestion against the routine use of systemic corticosteroids for
respiratory failure in COIVID-19, and a suggestion to use corticosteroids in the sicker population of COVID-
19 with ARDS. If clinicians use corticosteroids in ARDS, they should use lower dosing and shorter treatment
courses.
Recommendation:
43. In mechanically ventilated patients with COVID-19 and respiratory failure, we suggest using empiric
antimicrobials/antibacterial agents, over no antimicrobials (Weak recommendation, low quality evidence).
Remark: if the treating team initiates empiric antimicrobials, they should assess for de-escalation daily, and
re-evaluate the duration of therapy and spectrum of coverage based on the microbiology results and the
patient’s clinical status.
Rationale:
Introduction SARS-CoV2Traitement
Traitement étiologique
Diagnostic
Hydroxychloroquine and
azithromycin in COVID-19
Gautret et al. International Journal
of Antimicrobial Agents, 2020
GUIDELINES Un-edited accepted proof*
Recommendation
48. There is insufficient evidence to issue a recommendation on the use of recombinant rIFNs, alone or
in combination with antivirals, in critically ill adults with COVID-19.
Rationale:
Recombinant interferon, often combined with ribavirin therapy, has been used in patients with MERS and
SARS [179, 200-202]. Different preparations of recombinant rIFNs (rIFN-α2a, rIFN-α2b, rIFN-β1a and
rIFN-β1b) have shown activity against MERS-CoV in Vero and LLC-MK2 cells, and in a rhesus macaque
model of MERS-CoV infection [200, 201, 203]. The largest cohort of critically ill patients with MERS showed
that rIFN-α2a, rIFN-α2b, rIFN-β1a and ribavirin were not associated with lower mortality (OR 1.03, 95% CI
.73 to 1.44) or reduced viral clearance when adjusted for time-varying covariables [204]. The relative
effectiveness of different interferons against SARS-CoV-2 is unknown at this point.
In vitro data showed that rIFN-β displayed the strongest MERS-CoV inhibition among different rIFN
preparations (rIFN-α2b, rIFN-γ, rIFN-universal, and rIFN-α2a, rIFN-β), at 41 times lower than the
previously reported 50% inhibitory concentration (IC50) of rIFN-α2b [203, 205]. An RCT to examine the
effect of a combination of lopinavir /ritonavir and rIFN-β-1b on mortality of hospitalized patients with
MERS is currently recruiting patients [206]. Unpublished data indicate that IFN-β inhibits SARS-C0V-2 in
cell culture, and IFNs have been prioritized for study in COVID-19 by the WHO.
Recommendation
49. There is insufficient evidence to issue a recommendation on the use of chloroquine or
hydroxychloroquine in critically ill adults with COVID-19.
Rationale:
Introduction SARS-CoV2Traitement
Traitement étiologique
Diagnostic
ANTIVIRAUX
REMDESIVIR 200mg J1 puis 100mg/j
pendant 5-7j
LOPINAVIR/RITONAVIR
400mg/100mg x 2/j pendant 5-7j
A trial of Lopinavir-ritonavir in adult
with severe Covid-19
Wang et al. NEJM 2020
ANTIVIRAUX
Rationale:
Convalescent plasma obtained from patients who have recovered from COVID-19 has been suggested as a
potential therapy that may provide passive immunity from SARS-CoV2-specific antibodies [177].
Convalescent plasma has been used to treat several other viral infections, including those caused by SARS
coronavirus, avian influenza A (H5N1) virus, and influenza A (H1N1) pdm09 virus [178-182]. A recent meta-
analysis of observational studies using passive immunotherapy for the treatment of severe acute respiratory
infections of viral etiology suggests that convalescent plasma therapy was associated with reduction in
mortality (OR 0.25, 95% CI 0.14 to 0.45) [183]. During the current outbreak in China, convalescent plasma
was used in some patients with COVID-19 [184]. However, data on the efficacy and safety of convalescent
plasma are limited, and the target for sufficient levels of neutralizing antibody titers against SARS-CoV-2 is
unknown. A study on MERS concluded that use of convalescent plasma might be feasible but was
challenging due to a small pool of potential donors with sufficiently high antibody titers [185]. An RCT in
patients with confirmed Ebola virus disease showed that convalescent plasma, with unknown levels of
neutralizing antibodies, was not associated with improvement in survival [186]. Another RCT in patients with
seasonal influenza treated with high-titer versus low-titer anti-influenza immune plasma was terminated for
futility because of the lack of effect on the primary outcome measured by a 6-point ordinal scale of clinical
status on Day 7 [187]. Given the lack of convincing evidence from RCTs and the uncertainty surrounding the
optimal preparation of convalescent plasma and its safety, we suggest that it should not be routinely used in
treating patients with COVID-19 until more evidence is available.
Recommendation
47. In critically ill adults with COVID-19:
47.1. we suggest against the routine use of lopinavir/ritonavir (weak recommendation, low
quality evidence).
47.2. There is insufficient evidence to issue a recommendation on the use of other
antiviral agents in critically ill adults with COVID-19.
Rationale
35
END
Messages clés – Comment ne pas tuer les patients
Pplat statique/4h par pause inspiratoire manuelle 3s -> OBJECTIF < 30 cmH2O
PEP systématique pour tous les patients ≥ 8 cmH2O
Vt = 6 ml/kg de poids idéal théorique
Réglage de la FiO2 sur la saturation pulsée pour objectif Sat = 92%
Surveillance EtCO2 continue avec adaptation des objectifs sur PaCO2
Eviter les aspirations systématiques et non nécessaires
Eviter au maximum les ouvertures du circuit pour limiter le dérecrutement
Pas de remplissage vasculaire à l’aveugle
SI DOUTE
52333 / 54112 / 62647
36
SI DOUTE
52333 / 54112 / 62647
37
SI DOUTE
52333 / 54112 / 62647

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Pioche Pierre-Antoine - SDRA en contexte de SARS-CoV2

  • 1. Syndrome de Détresse Respiratoire Aiguë en contexte de SARS-CoV2 Dr GODET Thomas Dr AUDARD Jules Dr BLONDONNET Raïko PIOCHE Pierre-Antoine Pôle Médecine Péri-Opératoire 24 mars 2020
  • 2. DiagnosticIntroduction SARS-CoV2Traitement SDRA Léger Modéré Sévère Tous Mortalité à J28 29,6% 35,2% 40,9% 34,8% Epidemiology, Patterns of Care, and mortality for patients with ARDS in ICU in 50 countries Bellani et al. JAMA 2016
  • 3. DiagnosticIntroduction SARS-CoV2Traitement Le SDRA c’est quoi ? Atteinte directe - Pneumopathie infectieuse (bactérienne/virale) - Inhalation de liquide gastrique Atteinte indirecte - Choc septique - Polytraumatisé
  • 4. DiagnosticIntroduction SARS-CoV2Traitement Le SDRA c’est quoi ? Acute Respiratory Distress Syndrome Thompson et al. NEJM 2017 Epithélium bronchique Pneumocyte type I Surfactant Capillaire Bactérie, virus, champignon, trauma, liquide gastrique Rupture endothéliale Coagulation intravasculaire Inondation interstitielle Rupture de la membrane basale Œdème alvéolaire Inactivation du surfactant et lésion épithéliale SainExsudatif Macrophage alvéolaire Réponse inflammatoire L-T NETs ROS Elastase …Neutro Pneumocyte type II
  • 5. DiagnosticIntroduction SARS-CoV2Traitement Le SDRA c’est quoi ? Acute Respiratory Distress Syndrome Thompson et al. NEJM 2017
  • 7. Comment le diagnostiquer ? Acute Respiratory Distress Syndrome The Berlin Definition Ferguson et al. JAMA 2012 Léger Modéré Sévère Temps Début < 1 semaine, contexte clinique compatible Hypoxémie x = PaO2/FiO2 (mmHg) 200 < x ≤ 300 100 < x ≤ 200 ≤ 100 Chez un patient ventilé avec PEP ≥ 5cmH2O Origine de l’œdème Défaillance respiratoire non expliquée entièrement par une insuffisance cardiaque ou une surcharge volémique Anomalies radiologiques Opacités bilatérales non expliquées par des épanchements, atélectasies ou nodules Définition DiagnosticIntroduction SARS-CoV2Traitement
  • 9. DiagnosticIntroduction SARS-CoV2Traitement Quels moyens thérapeutiques ? TRAITEMENT ETIOLOGIQUE Quid du COVID 19 ? TRAITEMENT SYMPTOMATIQUE Oxygéner le sang Epurer le CO2 Protéger le poumon
  • 11. Ventilation à petits volumes Ventilation à hauts volumes Atélectasies Hétérogénéité Fuites d’air Conséquences structurelles Trasnformations épithéliales Dysfonction du surfactant Membranes hyalines Perte de l’épithélium bronchique Œdème pulmonaire Hyperperméabilité Alvéolo-capillaire Alvéole Alvéole Atélectasies Hyperdistension Alvéole Prolifération des fibroblastes DiagnosticIntroduction SARS-CoV2Traitement Ventilator-Induced Lung Injury Slutsky et al. NEJM 2013
  • 12. DiagnosticIntroduction SARS-CoV2Traitement Ventilator-Induced Lung Injury Slutsky et al. NEJM 2013 Ne pas être délétère ! Zone non aérée Zone pauvrement aérée Zone normalement aérée
  • 13. DiagnosticIntroduction SARS-CoV2Traitement 300 200 100250 150 50 PaO2/FiO2 Faible Volume Courant (6 ml.kg-1 de PIT) SDRA léger SDRA modéré SDRA sévère PEP élevée Décubitus Ventral Curarisation Manœuvre de Recrutement Alvéolaire ECMO PEP ≥ 5 cmH2O Thérapeutiques selon la sévérité Recommandations formelles A discuter
  • 14. DiagnosticIntroduction SARS-CoV2Traitement PRESSION DEBIT Pression de crête = Pmax Pression de plateau = Pplat Temps de pause télé-inspiratoire Mode en volume - VVC VTi Ouverture valve insp Fermeture valve expi Fermeture valve insp Ouverture valve expi Tinspiratoire Texpiratoire
  • 15. Prone positionning in ARDS Guérin et al. NEJM 2013 DiagnosticIntroduction SARS-CoV2Traitement Lien Vidéo : https://drive.google.com/open?id=1bByZrZmIK_SbnmLvzHqn1t sGD4a0woQQ
  • 16. Introduction SARS-CoV2Traitement Epidémiologie Diagnostic Asymptomatiques Insuffisance respiratoire 19% Admission en réaBesoin en O2 Ventilation mécanique SDRA 14% 5% 67% Hommes > 60 ans Comorbidités (Diabète, Cancer, ID) IOT + pathologies cardiovasculaires, Insuffisance Respiratoire chronique, HTA, Diabète, Cancer 1-2% Wu Z et al. JAMA, 2020
  • 17. Introduction SARS-CoV2Traitement Gestion du risque de contamination Diagnostic AIR DOIT SORTIR Protection du patient (immunodéprimés) AIR DOIT RENTRER Protection de l’environnement (contagion) SAS Pression négative Réa MIR Réa Adultes Estaing
  • 18. Introduction SARS-CoV2Traitement Gestion du risque de contamination Diagnostic Contamination des soignants ++ 10% Limiter le nombre de soignants FFP2 pour les procédures générant une aérosolisation* Chambre en pression négative (si dispo, 12 changements volume d’air/h 160L/s/patient) FFP 2 Pièce Faciale Filtrante Pourcentage de filtration d'aérosols (% minimum) Pourcentage de fuite vers l'intérieur (% maximum) FFP1 80 22 FFP2 94 8 FFP3 99 (EN 149-FFP3) 99,95 (EN 143-P3) 2 *Procédures aérosolisantes Intubation Bronchoscopie Aspi en système ouvert Ventilation manuelle (BAVU) Déconnection Trachéotomie Mise en Décubitus ventral +/- ONHD et VNI
  • 19. Introduction SARS-CoV2Traitement Gestion du risque de contamination Diagnostic POUR TOUTES LES AUTRES PROCEDURES
  • 20. Introduction SARS-CoV2Traitement Gestion du risque de contamination Diagnostic INTUBATION ORO-TRACHEALE Vidéolaryngoscope si disponible par opérateur expérimenté Lien vidéo : https://drive.google.com/open?id=1NM9Q-f_DR0fyxrOrNvIDUH9rw0_ntH3B
  • 21. Introduction SARS-CoV2Traitement Gestion du risque de contamination Diagnostic MONTAGE DU CIRCUIT DU RESPIRATEUR Filtre hydrophobe à haute capacité de filtration Filtre HEPA (machine) à remplacer toutes les 48h Filtres/Tuyaux à remplacer après chaque COVID19 + (anesthésie) Filtre HME (patient) à remplacer toutes les 48h ou si souillures
  • 22. Introduction SARS-CoV2Traitement Gestion du risque de contamination Diagnostic PRISE EN CHARGE PARAMEDICALE Lien vidéo : https://drive.google.com/open?id=1keADAc3me6fRajBaoY1Bpuj49LO5bIlT Mettre sur pause le ventilateur AVANT toute déconnection Garder le filtre connecté à la sonde d’intubation (si possible) Clamper la sonde d’intubation (si possible)
  • 23. Introduction SARS-CoV2Traitement Prise en charge respiratoire Diagnostic OXYGENOTHERAPIE Si SpO2 < 92% sans signe de détresse respiratoire O2Quels dispositifs ? Sonde Nasale 0,5 à 6 l/min Canule nasale Masque facial simple Max 10 l/min Masque facial avec réservoir Max 15 l/min OHD 35 à 60 l/min Intubation trachéale VNI ou CPAP O2Quels dispositifs ? Sonde Nasale 0,5 à 6 l/min Canule nasale Masque facial simple Max 10 l/min Masque facial avec réservoir Max 15 l/min OHD 35 à 60 l/min Intubation trachéale VNI ou CPAP O2Quels dispositifs ? nde sale 0,5 à 6 l/min Canule nasale Masque facial simple Max 10 l/min Masque facial avec réservoir Max 15 l/min OHD 35 à 60 l/min Intubation trachéale VNI ou CPAP
  • 24. acial rvoir min OHD 35 à 60 l/min Intubation trachéale VNI ou CPAP Introduction SARS-CoV2Traitement Prise en charge respiratoire – Recos 1/2 Diagnostic OXYGENATION NASALE A HAUT DEBIT +++ Attention, différent des recos françaises EVITER LA VNI Surmortalité, sauf si OHND indisponible 1 2 SURVEILLANCE CLINIQUE +++ MONITORAGE Fréquence respi, balancement thoraco- abdo, signes de lutte, hypovigilance 3 NE PAS RETARDER L’INTUBATION 4
  • 25. Introduction SARS-CoV2TraitementDiagnostic 24 oxygen use, and the potential to reduce equity if oxygen resources are depleted; the panel issued a strong recommendation against using oxygen to target SPO2>96%, and a strong recommendation to avoid lower SPO2<90%. Therefore, a reasonable SPO2 range for patients receiving oxygen 92% to 96%. Recommendation: 25. For adults with COVID-19 infection and acute hypoxemic respiratory failure, we suggest using HFNC over conventional oxygen therapy (weak recommendation, low quality evidence) Rationale: There is no direct evidence on patients with COVID-19, therefore, the panel used indirect evidence from the critically ill population to inform this recommendation. In an RCT comparing HFNC to conventional oxygen therapy for patients with acute hypoxic respiratory failure, HFNC resulted in reduced 90-day mortality (OR 0.42; 95% CI 0.21 to 0.85) but did not reduce the risk of intubation [70]. A systematic review and meta-analysis of 9 RCTs (2,093 patients) showed that HFNC reduces intubation compared to conventional oxygen (RR 0.85; 95% CI 0.74 to 0.99) but did not affect risk of death or ICU length of stay.[71-73] Even though evidence for mortality and length of stay is not endotracheal intubation, especially for nurses (OR 6.6, 95% Cl 2.3 to 18.9) [28, 74, 75]. While this is based mostly on retrospective observational studies, HFNC does not seem to confer an increased risk of transmission of disease. In studies evaluating bacterial environmental contamination, HFNC resulted in similar contamination risk as conventional oxygen [76]. In SARS, health care workers exposed to HFNC were not at increased risk of developing disease [74]. Finally, patients may find HFNC more comfortable or at least as comfortable as conventional oxygen therapy [70, 73]. Although some authors advised avoiding the use of HFNC in patients with COVID-19 due to fear of disease transmission, studies supporting this advice are lacking [77]. Recommendation: 26. For adults with COVID-19 and acute hypoxemic respiratory failure, we suggest using HFNC over NIPPV (weak recommendation, low quality evidence). Rationale: In adults with COVID-19 and acute respiratory failure, we suggest the use of HFNC over NIPPV. In an RCT comparing HFNC to NIPPV for patients with acute hypoxic respiratory failure, HFNC resulted in reduced mortality at 90 days (HR 2.50; 95% CI 1.31 to 4.78) but did not significantly affect the need for intubation (50% failure rate in NIPPV vs 47% in conventional oxygen and 40% in HFNC; p=0.18) [70]. Other meta-analysis comparing HFNC to NIPPV have shown HFNC to decrease the need for intubation of patients compared to NIPPV without significantly decreasing mortality or ICU length of stay [71]. Additionally, patients may find HFNC more comfortable than NIPPV [70]. Given the evidence for decreased risk of intubation for HFNC compared to NIPPV in acute hypoxemic respiratory failure and studies suggesting that NIPPV may confer greater risk for nosocomial infection of healthcare providers for infected patients, we suggest HFNC over NIPPV. However, any patients receiving HFNC or NIPPV should be monitored closely and cared for in a setting where intubation can be facilitated in the event of decompensation as failure rate may be high and emergent intubation in an uncontrolled setting may increase risk of nosocomial infection of Recommendations: 27. For adults with COVID-19 and acute hypoxemic respiratory failure, if HFNC is not available and no emergent indication for endotracheal intubation; we suggest a trial of NIPPV with close monitoring and short interval assessment for worsening respiratory failure (weak recommendation, very low quality evidence). 28. We were not able to make a recommendation regarding the use of helmet NIPPV compared to mask NIPPV, it is an option, but we are not certain about its safety or efficacy in COVID-19 29. For adults with COVID-19 infection receiving NIPPV or HFNC, we recommend close monitoring for worsening of respiratory status and early intubation in a controlled setting if worsening occurs (best practice statement). Rationale: Recommendations: 27. For adults with COVID-19 and acute hypoxemic respiratory failure, if HFNC is not available and no emergent indication for endotracheal intubation; we suggest a trial of NIPPV with close monitoring and short interval assessment for worsening respiratory failure (weak recommendation, very low quality evidence). 28. We were not able to make a recommendation regarding the use of helmet NIPPV compared to mask NIPPV, it is an option, but we are not certain about its safety or efficacy in COVID-19 29. For adults with COVID-19 infection receiving NIPPV or HFNC, we recommend close monitoring for worsening of respiratory status and early intubation in a controlled setting if worsening occurs (best practice statement). Rationale: Recommendations: 27. For adults with COVID-19 and acute hypoxemic respiratory failure, if HFNC is not available and no emergent indication for endotracheal intubation; we suggest a trial of NIPPV with close monitoring and short interval assessment for worsening respiratory failure (weak recommendation, very low quality evidence). 28. We were not able to make a recommendation regarding the use of helmet NIPPV compared to mask NIPPV, it is an option, but we are not certain about its safety or efficacy in COVID-19 29. For adults with COVID-19 infection receiving NIPPV or HFNC, we recommend close monitoring for worsening of respiratory status and early intubation in a controlled setting if worsening occurs (best practice statement). Rationale: Prise en charge respiratoire – Recos 1/2 Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) Alhazzani et al. ICM, 2020
  • 26. Introduction SARS-CoV2TraitementDiagnostic STRATEGIE RESTRICTIVE DE REMPLISSAGE VASCULAIRE SEANCES DE DECUBITUS VENTRAL DE 12 A 16h Pour SDRA modéré à sévère 5 6 CURARISATION (NON DEPOLARISANTS) intermittente ou continue pour 48H Pour SDRA modéré à sévère, pour faciliter la protection pulmonaire ou en cas de désynchronisation 7 Prise en charge respiratoire – Recos 2/2 MANŒUVRES DE RECRUTEMENT 8
  • 27. Introduction SARS-CoV2TraitementDiagnostic Prise en charge respiratoire – Recos 2/2 MANŒUVRES DE RECRUTEMENT 8 PRESSION 5 MODE VSAI Augmentation du temps d’apnée +++ PEP = 30-40cmH2O 10 – 30s
  • 28. Introduction SARS-CoV2TraitementDiagnosticClinicians can use the ARDS Network protocol strategies to determine the optimal PEEP level, other strategies are available such as decremental PEEP strategy, esophageal balloon, and electrical impedance tomography, however, the effect of using these techniques on clinical outcomes is unknown. Recommendation: 33. For mechanically ventilated adults with COVID-19 and ARDS, we suggest using a conservative fluid strategy over a liberal fluid strategy (weak recommendation, low quality evidence). Rationale: The optimal fluid strategy in COVID-19 is not known, however, it is plausible to assume that these patients will respond to fluid similar to other ARDS patients. Based on the limited data on COVID- 19, cardiac failure has been reported to be the cause of death in 40% of COVID-19 deaths, alone or with respiratory failure [45]. Another study showed that 44% of COVID-19 patients had arrhythmia[42]. The data suggest myocardial injury in some patients with COVID-19. In ARDS, few RCTs have been published that compare conservative or de-resuscitative and liberal fluid strategies. A recent systematic review included 5 RCTs enrolling 1,206 patients with ARDS, risk of death was similar in both groups, 28 % in the conservative fluid strategy group and 31.1% in the liberal strategy group (RR 0.91, 95% CI 0.77 to 1.07)[51]. This study included RCTs on critically ill patients with or without ARDS, they found that conservative fluid strategy increased ventilator free days ventilator free days (MD 1.82 days; 95 % CI 0.53 to 3.10 days) and reduced ICU length of stay (MD - 1.88 days, 95 % CI -0.12 to -3.64 days), compared to a liberal fluid strategy. There was no difference in harm, including renal failure between the two groups. The landmark trial on ARDS patients (FACTT) found a significant reduction in the duration of mechanical ventilation with conservative fluid strategy [108]. Furthermore, majority of patients with COVID-19 in the ICU are elderly, and may develop myocardial dysfunction which could limit their ability to handle large fluid 34. For mechanically ventilated adults with COVID-19 and moderate to severe ARDS, we suggest prone ventilation for 12 to 16 hours, over no prone ventilation (weak recommendation, low quality evidence). Rationale: The radiological findings of COVID-19 has been described in 81 patients, the radiological features seemed to progress over the course of 1 to 2 weeks of symptom onset from predominant ground glass opacities to a mixed pattern with consolidation mostly at the lung bases [109], which makes prone ventilation an attractive option. Prone ventilation theoretically makes ventilation more homogeneous by decreasing ventral alveolar distention and dorsal alveolar collapse [110]. Ultimately, reducing the difference between the dorsal and ventral transpulmonary pressures. In addition, prone ventilation reduces lung compression [111] and improve perfusion [112]. A recent study that described the clinical course of COVID-19 in the ICU showed the prone ventilation was used in 11.5% (6 out of 52 patients)[41], however, there are no studies to describe the clinical course of patients with COVID-19 who were ventilated in the prone position. A recent systematic review and meta-analysis of 9 RCTs (2,129 patients) showed that prone ventilation for at least 12 hours in patients with moderate to severe ARDS reduce mortality (5 RCTs; A protocol for proning should be used at each institution, based on the available resources and level of training. If prone ventilation is used, healthcare workers should be aware of complications such as pressure sores, vascular line and endotracheal tube displacement, facial edema, transient hemodynamic instability, corneal abrasions, brachial plexus injury, hemodialysis vascular access flow issues. In addition, clinicians should be familiar with absolute contraindications for prone ventilation such as unstable spine, open abdomen or open chest (i.e. surgery or trauma). Enteral nutrition via nasogastric or nasoduodenal tube can be continued during proning [117, 118]. Recommendations: 35. For mechanically ventilated adults with COVID-19 infection and moderate to severe ARDS: 35.1. We suggest using as needed intermittent boluses of neuromuscular blocking agents (NMBA), over a continuous NMBA infusion, to facilitate protective lung ventilation (weak recommendation, low quality evidence). 35.2. In case of persistent ventilator dyssynchrony, requirement of ongoing deep sedation, prone ventilation, or persistently high plateau pressures; we suggest using a continuous NMBA infusion for up to 48 hours (weak recommendation, low quality evidence). Rationale: Several professional societies issued recommendations on the use of NMBAs in ARDS [99, 119- Prise en charge respiratoire – Recos 2/2 38. For mechanically ventilated adults with COVID-19 and hypoxemia despite optimizing ventilation, we suggest using recruitment maneuvers, over not using recruitment maneuvers (weak recommendation, low quality evidence). 39. If recruitment maneuvers are used, we recommend against using staircase (incremental PEEP) recruitment maneuvers (strong recommendation, moderate quality evidence). Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) Alhazzani et al. ICM, 2020
  • 29. Introduction SARS-CoV2Traitement Monitorage et objectifs de soins – Recos 1/2 Diagnostic OBJECTIF SpO2 = 92-96% max Surmortalité dans l’hyperoxémie prolongée GAZOMETRIE 1 fois par jour (à 8h) 2 possibles si défaillance hémodynamique 1 2 ECONOMIE DES RESSOURCES en O2 – CIRCUIT FERME EN ANESTHESIE 3 Another study reported on 52 critically ill COVID-19 patients, 67% of patients had ARDS, 33 63·5% of patients received high-flow nasal cannula (HFNC), 56% invasive mechanical ventilation and 42% received NIPPV [41]. Risk factors for respiratory failure Risk factors associated with respiratory failure requiring mechanical ventilation were not clearly described in published reports, although from the limited available data, risk factors associated with a critical illness/ICU admission included older age (>60 years), male gender, presence of underlying comorbidities such as diabetes, malignancy, and immunocompromised state [1, 12, 41, 42]. The CDC reported an overall case-fatality rate (CFR) of 2.3%, with a CFR of 14.8% in patients 80 years or older. In critically ill patients, the CFR was 49.0% and higher than 50% in those who received invasive mechanical ventilation. The presence of pre-existing comorbid condition such as cardiovascular disease, diabetes, chronic respiratory disease, hypertension, and cancer were associated with higher risk of death [12]. Recommendation: 23. For adults with COVID-19, we suggest starting supplemental oxygen if the peripheral oxygen saturation (SPO2) is < 92%, and recommend starting supplemental oxygen if SPO2 is < 90% 24. For adults with COVID-19 and acute hypoxemic respiratory failure on oxygen; we recommend that SPO2 be maintained no higher than 96% (strong recommendation, moderate quality evidence). Rationale: Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19) Alhazzani et al. ICM, 2020
  • 30. Introduction SARS-CoV2TraitementDiagnostic OBJECTIF EtCO2 (30-35 mmHg) à corréler avec PaCO2 +++ Intérêt ++ de la capnographie en continu SURVEILLANCE CLINIQUE +++ 4 6 Monitorage et objectifs de soins – Recos 2/2 Pplat statique/4h pour OBJECTIF < 30 cmH2O5 Mesure par pause inspiratoire > 3s
  • 31. Introduction SARS-CoV2TraitementDiagnostic Monitorage et objectifs de soins – Recos 2/2 PRESSION DEBIT Pression de plateau = Pplat Temps de pause télé-inspiratoire 3s Pplat statique/4h pour OBJECTIF < 30 cmH2O5
  • 32. Introduction SARS-CoV2Traitement Traitement étiologique Diagnostic PLAQUENIL Hydroxychloroquine (antipaludéen, PR, lupus) Diminution du pH lysosomial et de la réplication du virus 200mg x 3/j pendant 10j + Azithromycine 500mg J1 puis 250mg/j J2-J5 Intensive Care Medicine GUIDELINES Un-edited accepted proof* 1.12 to 5.72) [147]. The only direct evidence comes from a retrospective cohort study of 201 patients with COVID-19 pneumonia. This study showed an association between corticosteroid use and lower mortality in patients with COVID-19 and ARDS (HR 0.38, 95%CI 0.20 to 0.72). However, the estimate was not adjusted for confounding factors [148]. The effect of corticosteroids in COVID-19 patients with sepsis or septic shock may be different. Recent systematic reviews and meta-analyses of RCTs in sepsis showed small improvements in mortality and faster resolution of shock with corticosteroid use, compared with not using corticosteroids [63, 149, 150] (see the previous section on hemodynamic support). It is widely recognized that corticosteroids have a range of adverse effects. In viral pneumonia in the ICU, several studies showed increase in viral shedding with corticosteroid use [151-153], potentially indicating viral replication, but the clinical implication of increased viral shedding is uncertain. Considering the above, the panel issued a suggestion against the routine use of systemic corticosteroids for respiratory failure in COIVID-19, and a suggestion to use corticosteroids in the sicker population of COVID- 19 with ARDS. If clinicians use corticosteroids in ARDS, they should use lower dosing and shorter treatment courses. Recommendation: 43. In mechanically ventilated patients with COVID-19 and respiratory failure, we suggest using empiric antimicrobials/antibacterial agents, over no antimicrobials (Weak recommendation, low quality evidence). Remark: if the treating team initiates empiric antimicrobials, they should assess for de-escalation daily, and re-evaluate the duration of therapy and spectrum of coverage based on the microbiology results and the patient’s clinical status. Rationale:
  • 33. Introduction SARS-CoV2Traitement Traitement étiologique Diagnostic Hydroxychloroquine and azithromycin in COVID-19 Gautret et al. International Journal of Antimicrobial Agents, 2020 GUIDELINES Un-edited accepted proof* Recommendation 48. There is insufficient evidence to issue a recommendation on the use of recombinant rIFNs, alone or in combination with antivirals, in critically ill adults with COVID-19. Rationale: Recombinant interferon, often combined with ribavirin therapy, has been used in patients with MERS and SARS [179, 200-202]. Different preparations of recombinant rIFNs (rIFN-α2a, rIFN-α2b, rIFN-β1a and rIFN-β1b) have shown activity against MERS-CoV in Vero and LLC-MK2 cells, and in a rhesus macaque model of MERS-CoV infection [200, 201, 203]. The largest cohort of critically ill patients with MERS showed that rIFN-α2a, rIFN-α2b, rIFN-β1a and ribavirin were not associated with lower mortality (OR 1.03, 95% CI .73 to 1.44) or reduced viral clearance when adjusted for time-varying covariables [204]. The relative effectiveness of different interferons against SARS-CoV-2 is unknown at this point. In vitro data showed that rIFN-β displayed the strongest MERS-CoV inhibition among different rIFN preparations (rIFN-α2b, rIFN-γ, rIFN-universal, and rIFN-α2a, rIFN-β), at 41 times lower than the previously reported 50% inhibitory concentration (IC50) of rIFN-α2b [203, 205]. An RCT to examine the effect of a combination of lopinavir /ritonavir and rIFN-β-1b on mortality of hospitalized patients with MERS is currently recruiting patients [206]. Unpublished data indicate that IFN-β inhibits SARS-C0V-2 in cell culture, and IFNs have been prioritized for study in COVID-19 by the WHO. Recommendation 49. There is insufficient evidence to issue a recommendation on the use of chloroquine or hydroxychloroquine in critically ill adults with COVID-19. Rationale:
  • 34. Introduction SARS-CoV2Traitement Traitement étiologique Diagnostic ANTIVIRAUX REMDESIVIR 200mg J1 puis 100mg/j pendant 5-7j LOPINAVIR/RITONAVIR 400mg/100mg x 2/j pendant 5-7j A trial of Lopinavir-ritonavir in adult with severe Covid-19 Wang et al. NEJM 2020 ANTIVIRAUX Rationale: Convalescent plasma obtained from patients who have recovered from COVID-19 has been suggested as a potential therapy that may provide passive immunity from SARS-CoV2-specific antibodies [177]. Convalescent plasma has been used to treat several other viral infections, including those caused by SARS coronavirus, avian influenza A (H5N1) virus, and influenza A (H1N1) pdm09 virus [178-182]. A recent meta- analysis of observational studies using passive immunotherapy for the treatment of severe acute respiratory infections of viral etiology suggests that convalescent plasma therapy was associated with reduction in mortality (OR 0.25, 95% CI 0.14 to 0.45) [183]. During the current outbreak in China, convalescent plasma was used in some patients with COVID-19 [184]. However, data on the efficacy and safety of convalescent plasma are limited, and the target for sufficient levels of neutralizing antibody titers against SARS-CoV-2 is unknown. A study on MERS concluded that use of convalescent plasma might be feasible but was challenging due to a small pool of potential donors with sufficiently high antibody titers [185]. An RCT in patients with confirmed Ebola virus disease showed that convalescent plasma, with unknown levels of neutralizing antibodies, was not associated with improvement in survival [186]. Another RCT in patients with seasonal influenza treated with high-titer versus low-titer anti-influenza immune plasma was terminated for futility because of the lack of effect on the primary outcome measured by a 6-point ordinal scale of clinical status on Day 7 [187]. Given the lack of convincing evidence from RCTs and the uncertainty surrounding the optimal preparation of convalescent plasma and its safety, we suggest that it should not be routinely used in treating patients with COVID-19 until more evidence is available. Recommendation 47. In critically ill adults with COVID-19: 47.1. we suggest against the routine use of lopinavir/ritonavir (weak recommendation, low quality evidence). 47.2. There is insufficient evidence to issue a recommendation on the use of other antiviral agents in critically ill adults with COVID-19. Rationale
  • 35. 35 END Messages clés – Comment ne pas tuer les patients Pplat statique/4h par pause inspiratoire manuelle 3s -> OBJECTIF < 30 cmH2O PEP systématique pour tous les patients ≥ 8 cmH2O Vt = 6 ml/kg de poids idéal théorique Réglage de la FiO2 sur la saturation pulsée pour objectif Sat = 92% Surveillance EtCO2 continue avec adaptation des objectifs sur PaCO2 Eviter les aspirations systématiques et non nécessaires Eviter au maximum les ouvertures du circuit pour limiter le dérecrutement Pas de remplissage vasculaire à l’aveugle SI DOUTE 52333 / 54112 / 62647
  • 36. 36 SI DOUTE 52333 / 54112 / 62647
  • 37. 37 SI DOUTE 52333 / 54112 / 62647