3. Challenge
• To deliver the right treatment in the right dose to the right patient
at the right time
• Mechanical ventilation
• can amplify the lung injury causing VILI
• can be adjusted to minimize VILI (and reduce mortality)
• By understanding the pathobiology of disease in individual patients
we can theoretically predict those most likely to benefit from a
given intervention
4. Limiting VILI
• Evaluate baby lung size (assessment of average lung strain)
• Evaluate parenchymal recruitability
• increase functional lung size
• prevent/limit atelectrauma
• Extent of lung inhomogeneity
• locally increase the stress and strain: stress raisers
Gattinoni et al. Crit Care 2017
Mead et al. JAP 70
8. Failure to demonstrate benefit may be
attributable to
• Absence of any treatment effect
• Chance
• Inadequate trial design
• Heterogeneity of treatment effect
27. P/V curve
• Complex procedure
• Risk of hemodynamic compromise and
lung injury
• Even if the PEEP is set properly using
the P/V curve, it must be reset as the
lung improves or deteriorates in
function
28.
29. Gattinoni et al. AJRCCM 1998
Respiratory mechanics
Response to PEEP
31. Trans-pulmonary pressure
DPaw = DPL + DPpl
airway driving pressure TPP changes in pleural pressure
changes in esophageal pressure
Editor's Notes
We will limit our analysis to ARDS patients, who are among the most problematic to manage among the mechanically ventilated patients. However, the principles of a safe treatment are equally applicable to all mechanically ventilated patients.
--- կարևոր է նշել, որ հիվանդներին խմբերի բաժանելու բազմաթիվ այլընտրանքային ուղիներ կան : Օրինակ ՝ խմբերը կարող են որոշվել վերջերս հայտնաբերված կենսանիշերի /բիոմարկերների/ պանելների միջոցով՝ ըստ հիվանդության ծանրության (մեղմ, չափավոր կամ խիստ ՝ Բեռլինի սահմանմամբ 2), կամ ՝ ըստ ավելի կոնկրետ պատճառ- հարուցիչների, ինչպիսիք են վնասվածքները կամ սեպսիսը : Ինչպես ընդգծեցին կոնսենսուսային վահանակի հեղինակները, թոքերի վնասվածքի հիմքում ընկած հստակ մեխանիզմները կարող են ազդել կլինիկական թերապևտիկ պատասխանի և կլինիկական բուժման ազդեցության վրա:
Որոշ դեպքերում դժվար է առանձնացնել ուղղակին անուղղակիից (սեպսիս և թոքաբորբ) : Շատ հիվանդներ ունեն ՍՇԴՀ –ի հարուցման բազմաթիվ պոտենցիալ դրդիչներ: Մեկ ուսումնասիրության մեջ ՍՇԴՀ-ի 21% հիվանդներն ունեցել են թոքերի վնասվածքի խառը պատճառներ: 5-ից ավելին, կարող են լինել ինչպես ուղղակի, այնպես էլ տարրեր
անուղղակի վնասվածք: Օրինակ ՝ ուղղակի վնասվածք՝ թոքաբորբը կարող է ունենալ անուղղակի բորբոքային ազդեցություններ հակադարձ թոքում: Այս տեսակի կլինիկական
տարասեռությունը դժվարացնում է կլինիկական ֆոկուսը սահմանմանը չհամապատասխանող ենթախմբերի համար և ներկայացնում է տվյալների մեկնաբանման մարտահրավերներ ՍՇԴՀ-ի տվյալների բազային :
Մահացությունը ավելի մանրամասն ուսումնասիրելու համար մենք համեմատեցինք ուղիղ թոքային ռիսկի գործոններ (թոքաբորբ կամ ասպիրացիա, n454) ունեցող անձանց ՝ ՍԹԱ / ՍՇԴՀ ի ոչ թոքային ռիսկի գործոններ ունեցողների հետ (n 448) (Աղյուսակ 3): Մահացության դեպքերի մակարդակը եղել է համանման ևթոքային (36%) և ոչ թոքային ռիսկի (34%) գործոններով անձանց պարագայում
(p 0.57; OR 1.1; 95% CI 0.8 to 1.4) : Վիճակագրական փոխազդեցություն չի նկատվել օդափոխիչով բուժման ռազմավարության և համատարբերակների (էջ 0.61)
վերահսկումնից հետո ՝թոքային կամ ոչ թոքային ռիսկի գործոնների ազդեցության միջև:
Երբ կլինիկական ռիսկի գործոնները վերադասակարգվցին որպես վարակի հետ կապված (սեպսիս, թոքաբորբ) կամ վարակի հետ չկապված պայմաններ (վնասվածք, ասպիրացիա, այլ),
այս պարագայում էլ չի եղել վիճակագրական փոխազդեցություն օդափոխիչով բուժում և ռիսկի գործոն բազմաբնույթ վերլուծության միջև (էջ 0,52):
To further examine mortality, we compared subjects with
direct pulmonary risk factors (pneumonia or aspiration, n
454) and those with nonpulmonary risk factors for ALI/ARDS
(n 448) (Table 3). The case-fatality rate was similar among
persons with pulmonary (36%) and nonpulmonary risk factors
(34%) (p 0.57; OR 1.1; 95% CI 0.8 to 1.4). There was no statistical
interaction between ventilator treatment strategy and
having pulmonary or nonpulmonary risk factors, after controlling
for covariates (p 0.61). When the clinical risk factors
were reclassified as infection-related (sepsis, pneumonia) or
non-infection-related conditions (trauma, aspiration, other),
there was also no statistical interaction between ventilator
treatment and risk factor in multivariate analysis (p 0.52).
IMPORTANCE The effects of recruitment maneuvers and positive end-expiratory pressure
(PEEP) titration on clinical outcomes in patients with acute respiratory distress
syndrome (ARDS) remain uncertain.
OBJECTIVE To determine if lung recruitment associated with PEEP titration according to the
best respiratory-system compliance decreases 28-day mortality of patients with moderate to
severe ARDS compared with a conventional low-PEEP strategy.
DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized trial conducted at 120
intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017,
enrolling adults with moderate to severe ARDS.
INTERVENTIONS An experimental strategy with a lung recruitment maneuver and PEEP
titration according to the best respiratory–system compliance (n = 501; experimental group)
or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode
until weaning.
MAIN OUTCOMES AND MEASURES The primary outcomewas all-cause mortality until 28 days.
Secondary outcomes were length of ICU and hospital stay; ventilator-free days through day
28; pneumothorax requiring drainage within 7 days; barotrauma within 7 days; and ICU,
in-hospital, and 6-month mortality.
RESULTS A total of 1010 patients (37.5%female; mean [SD] age, 50.9 [17.4] years) were
enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group
and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.20; 95%
CI, 1.01 to 1.42; P = .041). Compared with the control group, the experimental group strategy
increased 6-month mortality (65.3%vs 59.9%; HR, 1.18; 95%CI, 1.01 to 1.38; P = .04),
decreased the number of mean ventilator-free days (5.3 vs 6.4; difference, −1.1; 95%CI, −2.1
to −0.1; P = .03), increased the risk of pneumothorax requiring drainage (3.2%vs 1.2%;
difference, 2.0%; 95%CI, 0.0%to 4.0%; P = .03), and the risk of barotrauma (5.6%vs 1.6%;
difference, 4.0%; 95%CI, 1.5%to 6.5%; P = .001). There were no significant differences in
the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality.
CONCLUSIONS AND RELEVANCE In patients with moderate to severe ARDS, a strategy with
lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause
mortality. These findings do not support the routine use of lung recruitment maneuver and
PEEP titration in these patients.
Whole lung helicoidal CT scans acquired during end-expiratory breath holds in swine. Representative images were selected considering
anatomical landmarks. The low positive end-expiratory pressure (PEEP) level and the subsequent increase in abdominal weight progressively increased
the amount of nonaerated tissue. Setting the PEEP according to a decremental PEEP trial preceded by a recruitment maneuver was able to restore lung
morphology. Poorly aerated tissue levels were minimally affected throughout the study protocol. #p < 0.05 Compared with baseline; §p < 0.05 Compared
with PEEP 5.
Objectives: Atelectasis develops in critically ill obese patients
when undergoing mechanical ventilation due to increased pleural
pressure. The current study aimed to determine the relationship
between transpulmonary pressure, lung mechanics, and lung
morphology and to quantify the benefits of a decremental positive
end-expiratory pressure trial preceded by a recruitment maneuver.
Design: Prospective, crossover, nonrandomized interventional
study.
Setting: Medical and Surgical Intensive Care Units at Massachusetts
General Hospital (Boston, MA) and University Animal
Research Laboratory (São Paulo, Brazil).
Patients/Subjects: Critically ill obese patients with acute respiratory
failure and anesthetized swine.
Interventions: Clinical data from 16 mechanically ventilated critically
ill obese patients were analyzed. An animal model of obesity
with reversible atelectasis was developed by placing fluid filled
bags on the abdomen to describe changes of lung mechanics,
lung morphology, and pulmonary hemodynamics in 10 swine.
Measurements and Main Results: In obese patients (body mass
index, 48 ± 11 kg/m2), 21.7 ± 3.7 cm H2O of positive end-expiratory
pressure resulted in the lowest elastance of the respiratory
system (18.6 ± 6.1 cm H2O/L) after a recruitment maneuver and
decremental positive end-expiratory pressure and corresponded
to a positive (2.1 ± 2.2 cm H2O) end-expiratory transpulmonary
pressure. Ventilation at lowest elastance positive end-expiratory
pressure preceded by a recruitment maneuver restored endexpiratory
lung volume (30.4 ± 9.1 mL/kg ideal body weight) and
oxygenation (273.4 ± 72.1 mm Hg). In the swine model, lung collapse
and intratidal recruitment/derecruitment occurred when
the positive end-expiratory transpulmonary pressure decreased
below 2–4 cm H2O. After the development of atelectasis, a decremental
positive end-expiratory pressure trial preceded by lung
recruitment identified the positive end-expiratory pressure level
(17.4 ± 2.1 cm H2O) needed to restore poorly and nonaerated
lung tissue, reestablishing lung elastance and oxygenation while
avoiding increased pulmonary vascular resistance.
Conclusions: In obesity, low-to-negative values of transpulmonary
pressure predict lung collapse and intratidal recruitment/
derecruitment. A decremental positive end-expiratory pressure
trial preceded by a recruitment maneuver reverses atelectasis,
improves lung mechanics, distribution of ventilation and oxygenation,
and does not increase pulmonary vascular resistance.
The relationship between oxygenation response and mortality depends on whether the
positive end-expiratory pressure (PEEP) was increased. Changes in oxygenation after increased
PEEP are strongly associated with adjusted mortality (cyan line) whereas changes in oxygenation with
decreased or unchanged PEEP are not associated with adjusted mortality (blue line) (P = 0.017 for
interaction). Shaded zones represent 95% confidence intervals. P/F = ratio of arterial partial pressure
of oxygen and the fraction of inspired oxygen.
Very recently, systematic PP performed in ARDS patients with PF ratio lower than 150 has been shown to decrease mortlaity
In this study, the mean PF ratio before PP was 100, suggesting that PP is efficient in very severe ARDS
The use of lung compliance to identify the
optimally protective mechanical breath has recently been reassessed in a retrospective
paper analyzing the parameters associated with increased mortality. In this statistical
analysis by Amato et al., 3562 patients enrolled in nine previous ARDSnet studies were
studied, and it was shown that higher plateau pressure (Pplat) was not always associated
with increased mortality nor was higher PEEP always protective, whereas driving pressure
(ΔP = tidal volume/respiratory-system compliance) was strongly associated with survival
Pressure/volume (P/V) curve from an ARDS patient showing both the lower and upper inflection points
(PFLEX). The hypothesis is that the lower PFLEX is the critical alveolar opening point and the upper PFLEX the point
at which alveoli begin to over-distend, however, this hypothesis has been challenged [97, 98]. In this patient,
ventilation with a high tidal volume (Vt = 10 ml/kg plus PEEPIDEAL= 15 cmH2O) would cause over-distension
since ventilation is well above the upper PFLEX. Ventilation with low Vt and PEEPIDEAL was below the upper PFLEX.
The calculated lung compliance was increased from 31.6 to 40 with low Vt ventilation
To assess the possible differences in respiratory mechanics between the acute respiratory distress
syndrome (ARDS) originating from pulmonary disease (ARDSp) and that originating from extrapulmonary
disease (ARDSexp) we measured the total respiratory system (Est,rs), chest wall (Est,w) and
lung (Est,L) elastance, the intra-abdominal pressure (IAP), and the end-expiratory lung volume
(EELV) at 0, 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) in 12 patients with ARDSp
and nine with ARDSexp. At zero end-expiratory pressure (ZEEP), Est,rs and EELV were similar in both
groups of patients. The Est,L, however, was markedly higher in the ARDSp group than in the ARDSexp
group (20.2
6 5.4 versus 13.8
6 5.0 cm H2O/L, p
, 0.05), whereas Est,w was abnormally increased in
the ARDSexp group (12.1
6 3.8 versus 5.2
6 1.9 cm H2O/L, p
, 0.05). The IAP was higher in ARDSexp
than in ARDSp (22.2
6 6.0 versus 8.5
6 2.9 cm H2O, p
, 0.01), and it significantly correlated with
Est,w (p
, 0.01). Increasing PEEP to 15 cm H2O caused an increase of Est,rs in ARDSp (from 25.4
6 6.2
to 31.2
6 11.3 cm H2O/L, p
, 0.01) and a decrease in ARDSexp (from 25.9
6 5.4 to 21.4
6 55.5 cm
H2O/L, p
, 0.01). The estimated recruitment at 15 cm H2O PEEP was
20.031
6 0.092 versus 0.293
6
0.241 L in ARDSp and ARDSexp, respectively (p
, 0.01). The different respiratory mechanics and response
to PEEP observed are consistent with a prevalence of consolidation in ARDSp as opposed to
prevalent edema and alveolar collapse in ARDSexp.
The authors speculated that PEEP in the setting of direct lung injury may lead to alveolar stretch in relatively normal areas of lung, causing secondary lung injury, whereas
PEEP in the setting of indirect lung injury, applied more evenly across a more homogenously affected lung, results in increased alveolar recruitment. These data are further supported by additional data showing that patients with direct ARDS have reduced lung compliance and increased chest wall compliance relative to those with indirect ARDS.
A gauche: *p , 0.05 versus PEEP 0 cm H2O; **p , 0.01 versus PEEP 0 cm H2O. Comparison between the two groups; mp , 0.05 versus Group 1; mmp , 0.01 versus Group 1.
ARDS of pulmonary versus extrapulmonary origin at ZEEP. As shown in Figure 1, Est,rs was similar for both types of ARDS at ZEEP (25.4 6 6.2 versus 26 6 5.4 cm H2O/L, p 5
NS), but Est,L was higher in ARDSp (20.2 6 5.4 versus 13.8 6 5.0 cm H2O/L in ARDSexp, p , 0.01) indicating a stiffer lung. Est,w was more than twofold higher in ARDSexp than in
ARDSp (12.1 6 3.8 versus 5.2 6 1.9 cm H2O/L, p , 0.01), indicating a stiffer chest wall. This latter finding was possibly due to higher intra-abdominal pressure, which amounted to 22.2 6 6.0 and 8.5 6 2.9 cm H2O in ARDSexp and ARDSp, respectively (p , 0.01).
PEEP response in ARDS of pulmonary or extrapulmonary origin. Increasing PEEP from 0 to 15 cm H2O led to opposite effects on elastance in the two types of ARDS, as shown in
Figure 1. In ARDSp (upper panel), increasing PEEP caused an increase of Est,rs mainly caused by an increase in Est,L whereas in ARDSexp (lower panel) PEEP resulted in a significant decrease in Est,rs caused by the reduction in both Est,L and Est,w. Increasing PEEP from 0 to 15 cm H2O led to a slight increase in intra-abdominal pressure (p , 0.01) in both groups and amounted, at 15 cm H2O PEEP, to 10.0 6 3.4 and 24.3 6 6.1 cm H2O in ARDSp and ARDSexp, respectively. These results indicate a stiffer lung in ARDSp, which does not improve with PEEP, while in ARDSexp there is a stiffer thoracoabdominal cage and a more compliant lung, which both improve with increasing PEEP.
A droite: Pressure-volume (P-V) relationship in patients with ARDS caused by pulmonary disease, (Group 1, left panel) and with ARDS caused by extrapulmonary disease (Group 2, right panel) as a function of PEEP. As shown, in Group 1, the P-V relationships follow systematically the same line, with a slope decreasing at 15 cm H2O (i.e., decreased compliance), whereas the P-V relationships of Group 2 patients are shifted upwards as a function of PEEP (i.e., at the same pressure of volume is greater at higher PEEP, suggesting recruitment). The slope of P-V relationship increases with PEEP, indicating the compliance improvement.
As shown in Figure 3 (left panel), the pressure-volume relationship of the total respiratory system of patients with ARDSp was essentially the same at each PEEP level. This suggests that, at end-expiration, PEEP keeps already open pulmonary units more inflated, but no recruitment occurs. This pattern is substantially different in ARDSexp
(right panel) where an upwards shift of the pressure-volume curve of the total respiratory system was observed, indicating significant recruitment of pulmonary units by PEEP. The difference in response between ARDSp and ARDSexp with regard to end-expiratory lung volume and recruitment is shown in Table 5.
TPP: to insufflate the lung
DPpl: to move the chest wall
- tidal ΔPL should probably be kept below 15–20 cmH2O in patients with homogeneous lung parenchyma (normal, postsurgical patients)
- tidal ΔPL should possibly below 10–12 cmH2O in patients with inhomogeneous lung parenchyma (ARDS)
