VENTILATIA MECANICA IN ARDS

Dr. Adi Ciumanghel

Sp. Sf. Spiridon Iasi

 AECC DEFINITION-1994

• ALI
– Acute onset
– Bilateral chest infiltrates
– PCWP ≤ 18mm Hg or absence of clinical e/o LA hypertension
– PaO2 : FiO2 ratio ≤ 300

• ARDS
– PaO2 : FiO2 ratio ≤ 200
– And all the above

• Independent of PEEP

» Bernard et al, Am J Respir CCM; 1994;149:818-24

BERLIN DEFINITION
 BERLIN DEFINITION

• Mild
• Moderate
• Severe

• Compared with the AECC definition, the final Berlin Definition had better
predictive validity for mortality, with an area under the ROC of 0.577 (95%
CI, 0.561-0.593) vs 0.536 (95% CI, 0.520-0.553;P<.001)

Gordon D. Rubenfeld, MD,JAMA. 2012;307(23):doi:10.1001/jama.2012.5669

 OBSERVED 60-DAY MORTALITY-2944 PATIENTS

Spragg RG, Bernard GR, CheckleyW, et al. Beyond mortality: future clinical
research in acute lung injury. Am J Respir Crit Care Med 2010;181(10):1121–7
 ETIOLOGY
• Direct pulmonary causes
– pneumonia (bacterial or viral)
– aspiration pneumonitis
– inhalation injury/ Near drowning
– lung contusion

• Indirect extrapulmonary causes

– extrapulmonary sepsis
– trauma with shock
– burn injury
– blood transfusion
– drug overdoses
– pancreatitis
 PATHOPHYSIOLOGY
• The acute phase of acute lung injury and
ARDS is characterized by the influx of protein-
rich edema fluid into the air spaces as a
consequence of increased permeability of the
alveolar–capillary barrier
 Treatments of ARDS

Non-pharmacologic Pharmacologic
•Low tidal volumes •Corticosteroids
•High PEEP •Nitric oxide
•Recruitment maneuvers •Alkali Therapy
•Prone positioning •Neuromuscular blockade
•VC vs PCV •Ketoconazole
•High Frequency Oscillatory Ventilation (HFOV) •Lisofylline
•Airway Pressure Release Ventilation (APRV) •Oxepa
•Conservative fluids •Antioxidants
•Renal Replacement Therapy •Neutrophil elastase inhibition
•Early enteral feeding •Exogenous surfactant
•PA Catheter •Liquid ventilation
•ECMO •Inhaled β-agonists
•Statins
Treatments of ARDS with Mortality Benefit

Non-pharmacologic Pharmacologic
•Low tidal volumes •Corticosteroids
•High PEEP •Nitric oxide
•Recruitment maneuvers •Alkali Therapy
•Prone positioning •Neuromuscular blockade
•VC vs PCV •Ketoconazole
•High Frequency Oscillatory Ventilation (HFOV) •Lisofylline
•Airway Pressure Release Ventilation (APRV) •Oxepa
•Conservative fluids •Antioxidants
•Renal Replacement Therapy •Neutrophil elastase inhibition
•Early enteral feeding •Exogenous surfactant
•PA Catheter •Liquid ventilation
•ECMO •Inhaled β-agonists
•Statins
 VILI
• Oxidant injury- keep FiO2 <60

• Barotrauma- keep alveolar inflation pressures <35 cm H2O

• Volutrauma- Baby lung concept or stretch injury

• Atelectrauma- repeated opening and closing

• Biotrauma- release of inflammatory mediators and bacterial translocation

 TIDAL VOLUME

ARDSNET: NEJM May 2000

ARMA

75 ICU

• 6cc/kg PBW • 12cc/kg PBW

• N= 432 • N= 429
• Death before discharge 31% • 39.8%
• Breathing w/o assistance day 28 • 55%
= 65.7%
• Plateau Pressure (cm of H2O) • 33±9
25±7
• Lower IL-6 levels
 TIDAL VOLUME

• Meta-analysis -2004 – Petrucci N.

• 5 RCT – 1202 adult pts.
• TV<7ml/kg si P plat<30 cm H20 (protective)
• TV=10-15 ml/kg
• Mortality 28 days- 27,4% vs 37%
• Hospital mortality 34,5% vs 43,2%

• The mortality not different if the P plat<31 cm H20 in control TV

group
• Not same PEEP
Meta-analysis -2004 – Petrucci N.
Meta-analysis -2004 – Petrucci N.
 TIDAL VOLUME
• Pelosi P. , Putensen C. - 2009 Ann Intern Med
• 9 RCT:
• Hight vs Low TV same PEEP – 4 RCT → 1149 pts.
• Hight vs Low PEEP during low TV – 3 RCT → 2299pts.
• Hight TV and Low PEEP vs Low TV and Hight PEEP –2 RCT→148pts

• Lower TV ventilation reduced hospital mortality compared with higher TV

at similar PEEP (OR = 0,75; p=0,02)
• Higher PEEP did not reduce hospital mortality compared with lower PEEP
using low TV ventilation (OR=0,86; p=0,08)
• Higher PEEP reduced need for rescue therapy to prevent life-threatening
hypoxemia (OR=0,51; p<0,001)
 ARDS
Mechanical Ventilation
• Initial tidal volumes of 8 mL/kg predicted body weight in kg,
calculated by:
– [2.3 *(height in inches - 60) + 45.5 for women or + 50 for men].
• Respiratory rate up to 35 breaths/min
– expected minute ventilation requirement (generally, 7-9 L /min)
• Set positive end-expiratory pressure (PEEP) to at least 5 cm H2O
(but much higher is probably better)
• FiO2 to maintain an arterial oxygen saturation (SaO2) of 88-95%
(paO2 55-80 mm Hg).
– Titrate FiO2 to below 70% when feasible.
• Over a period of less than 4 hours, reduce tidal volumes to 7
mL/kg, and then to 6 mL/kg.
 PLATEAU PRESSURES

Hager DN et al. Tidal Volume Reduction in Patients with Acute Lung Injury
When Plateau Pressures Are Not High. AJRCCM 2005. Vol 172 1241-1245
 ARDS
Mechanical Ventilation
• Plateau pressure (measured every 4 h after change PEEP/TV
during an inspiratory hold of 0.5 sec) less than 30 cm H2O,
– High plateau pressures vastly elevate the risk for harmful
alveolar distension ( volutrauma).
• If plateau pressures remain elevated after following the above
protocol, further strategies should be tried:
– Reduce tidal volume, to as low as 4 mL/kg by 1 mL/kg
stepwise increments.
– Sedate the patient to minimize ventilator-patient
dyssynchrony.
– Consider other mechanisms for the increased plateau
pressure
787 patients from ARDS Network study
 PEEP
• EXPRESS
• LOVS
• ALVEOLI

• 2010 meta-analysis of 3 randomized trials (n=2,299) testing higher

vs. lower PEEP in patients with acute lung injury or ARDS, in which
ARDS patients receiving higher PEEP had a strong trend toward
improved survival

• Meta-analysis of these trials revealed no difference in hospital

mortality, although higher PEEP was associated with reduced ICU
mortality, total rescue therapies, and death after rescue therapy

• Briel M, Meade M, Mercat A, et al. Higher vs lower positive end-expiratory pressure in

patients with acute lung injury and acute respiratory distress syndrome. JAMA
2010;303(9):865–73.
 Positive End-Expiratory Pressure Setting in Adults With Acute
Lung Injury and Acute Respiratory Distress Syndrome:EXPRESS

• Multicenter RCT- 37 ICU France

• 767 adults pts. ALI/ARDS

• Moderate PEEP strategy= 5-9 cm H2O- oxygenation targets

• PEEP set to reach P plat=28-30 cm H20- highest regardless
efect on oxygenation

• 28 day mortality 31,2% vs 27,8% (RR=1,12; p=0,31)

• Reduced duration of MV and organ failure
 Positive End-Expiratory Pressure Setting in Adults With Acute
Lung Injury and Acute Respiratory Distress Syndrome:EXPRESS
 Ventilation Strategy Using Low Tidal Volumes, Recruitment
Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung
Injury and Acute Respiratory Distress Syndrome:LOVE
 Ventilation Strategy Using Low Tidal Volumes, Recruitment
Maneuvers, and High Positive End-Expiratory Pressure for Acute Lung
Injury and Acute Respiratory Distress Syndrome(LOVE)
Higher vs Lower End-Epiratory Pressure in Patients with
the Acute respiratory Distress Syndrome (ALVEOLI)
Higher vs Lower End-Epiratory Pressure in Patients with
the Acute respiratory Distress Syndrome (ALVEOLI)
Higher vs Lower End-Epiratory Pressure in Patients with the
Acute respiratory Distress Syndrome (ALVEOLI)
 Meta-analysis results
EXPRESS/LOVE/ALVEOLI
 A simpler way to set PEEP?

1. Perform RM

2. Decremental PEEP trial while measuring dynamic compliance

3. Identify PEEP associated with highest compliance

4. Repeat RM and set PEEP at or just above PEEP determined above

•This PEEP corresponds to CT scan findings just before atelectasis appears . . .

in pigs after lung lavage.

Suarez-Sipmann et al. Crit Care Med 2007;35:214-221

 VC vs PCV

PCV: variable flow so more comfortable if dyssynchrony,

prolong i time for oxygenation, control peak pressures
 VC vs PCV
• RCT multicenter, 79 patients with ARDS
• PCV (n-37) versus VCV (n=42). P plat ≤ 35 cm H2O
• No difference in mortality, trend to more renal failure in VCV group
• BUT patients in VCV group had a higher in-house mortality related to
higher number of extra-pulmonary organ failures (78% vs 51%)
• Also TV 8cc/kg of weight
 RECRUITMENT
• A recent systematic review analyzed 40 studies that evaluated RMs; 4 were
RCTs, 32 prospective studies, and 4 retrospective cohort studies

• The sustained inflation method (ie, continuous positive airway pressure [CPAP]
of 35–50 cm H2O for 20–40 seconds) was used most often (45%), followed by
high pressure control (23%), incremental PEEP (20%), and a high VT/sigh (10%)

• Current evidence suggests that that RMs should not be routinely used on all
ARDS patients unless severe hypoxemia persists or as a rescue maneuver to
overcome severe hypoxemia, to open the lung when setting PEEP, or following
evidence of acute lung derecruitment such as a ventilator circuit disconnect
• Pts with lot of recruitable lung/ little recruitable lung CT

• Fan E, Wilcox ME, Brower RG, et al. Recruitment maneuvers for acute lung injury.Am J Respir Crit
Care Med 2008;178(11):1156–63.
 PRONE POSITIONING

Computed tomography scan of the lungs showing ARDS when the patient is lying
supine (left) and prone (right).
Gattinoni L, Protti A. Ventilation in the prone position:for some but not for all? CMAJ 2008;178(9):1174–6)
 PRONE POSITIONING

• Placing patients who require mechanical ventilation in the prone rather

than the supine position improves oxygenation.
• In this trial, the investigators found a benefit with respect to all-cause
mortality with this change in body position in patients with severe ARDS.
 Kaplan–Meier Plot of the Probability of Survival from Randomization to Day 90.

PRONE POSITIONING

Guérin C et al. N Engl J Med 2013;368:2159-2168

Guérin C et al. N Engl J Med 2013;368:2159-2168

 Evidence for Proning
• The Prone-Supine II Study is the largest clinical trial (N 5342) in adult ARDS
patients, conducted in 23 centers in Italy and 2 in Spain
• 20 hours/day

• Similar 28-day mortality- 31.0% vs 32.8%; RR 0.97; (95% CI 0.84–1.13;

p=.72)
• Mortality in severe hypoxemia was decreased in the prone group-37.8% in
the prone group and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66–
1.14 p=.31)

• Taccone P, Pesenti A, Latini R, et al. Prone positioning in patients with moderate and severe acute
respiratory distress syndrome: a randomized controlled trial. JAMA 2009;302:1977–84.
 ARDS
Mechanical Ventilation

• Neuromuscular blockers in early acute

respiratory distress syndrome.
N Engl J Med, 2010;363:1107-16.

– This multicenter RCT of 340 patients with severe ARDS found

early use of 48 hours of neuromuscular blockade reduced
mortality compared to placebo (NNT of 11 to prevent one
death at 90 days in all patients, and a NNT of 7 in a
prespecified analysis of patients with a PaO2:FiO2 less than
120).
ECMO
 ECMO
• ECMO is supportive care and is not intended as a primary
ARDS treatment

• CESAR trial:

– Patients were randomized to either conventional care at 1 of 68

tertiary care centers or to a single center using a treatment
protocol that included ECMO
– The trial was stopped for efficacy after 180 patients(90 ECMO; 90
conventional MV)
– Survival without severe disability at 6 months was 47%
conventional MV vs 63% ECMO
– NNT =6
– Peek GJ, Mugford M, Tiruvoipati R, et al. Efficacy and economic assessment of conventional
ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure
(CESAR): a multicentre randomised controlled trial. Lancet 2009;374(9698):1351–63.