**5. The hole of low respiratory system compliance in ARDS severity stratification**

Other factors that are associated with severe ARDS are respiratory system compliance of less than 20 mL/cm H<sup>2</sup> O, pulmonary dead space fraction greater than 0.60, as well as high APACHE II and SAPS II score as well as multiple organ failures (the higher the organ failures, the higher the patient mortality) [1–4].

Ichikado [8] showed that fibroproliferation signs in high-resolution CT evaluation of early ARDS patients were correlated with higher mortality and ventilator dependency. The lung SAFE study [3], an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted in 459 ICUs from 50 countries across five continents showed that 2.377 out of 29.144 patients developed ARDS in the first 48 h and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2–31.9%); of moderate ARDS, 46.6% (95% CI, 44.5–48.6%); and of severe ARDS, 23.4% (95% CI, 21.7–25.2%). The cumulative frequency distribution of tidal volume was similar in patients in each severity category, with 65% of patients with acute respiratory distress syndrome (ARDS) receiving a tidal volume of 8 mL/kg of predicted body weight or less. In contrast, a right shift of the cumulative frequency distribution curves of plateau pressures was seen for increasing ARDS severity category, with plateau pressure of more than 30 cm H<sup>2</sup> O in 8.5% of patients for which these data were available. There was a lower likelihood of survival to day 28 with increasing severity of acute respiratory distress syndrome (ARDS) at day 1. Patients with a driving pressure of greater than 14 cm H2 O on day 1 of ARDS criteria had a higher mortality. Taking into consideration, these data that tidal volume ventilation was similar across the ARDS severity but inspiratory driving pressure less than 14 cm H2 O was associated with decreased mortality of those patients one could argue that in the future tidal volume should be titrated according to the derived driving inspiratory pressure.

28-day mortality in 56 ARDS patients. They observed that PEEP titration to target positive end-expiratory transpulmonary pressures resulted in both improved elastance and driving

However, future studies regarding the evaluation of respiratory system and transpulmonary driving pressure in ARDS patients with normal and increased abdominal pressure and various degrees of respiratory system compliance is still needed in order to establish the value of both as a bedside ventilator target as well as a prognosticator of evolution and mortality of

 **and multiple organ** 

Severe Acute Respiratory Distress Syndrome http://dx.doi.org/10.5772/intechopen.77071

levels with

53

table reduced

pressures and was associated with improved 28-day mortality.

**6. The hole of increased dead space, high PaCO2**

and progressively lower in sepsis, pneumonia and trauma).

**8. Treating the severe ARDS patient**

Increased dead space in the first day of mechanical ventilation, increased PaCO<sup>2</sup>

**7. Does the risk factor for ARDS influence the patient mortality rate?**

Recently, Villar and colleagues [11] showed in a cohort of 778 patients that severe ARDS occurred in about 37.5% at ARDS diagnosis and after 24 h of ARDS onset 20.8% and moderate to severe ARDS had an overall mortality of 38.8%. They also showed that the underlying cause of ARDS influence in the mortality ratio (the mortality ratio was higher in pancreatitis

Low-tidal ventilation (≤6 mL/kg of predicted body weight) must be initiated as soon as the ARDS patient is intubated and mechanically ventilated. The predicted body weight (PBW) can be calculated as follows: for women, PBW = 45.5 + 0.91 (height in centimeters—152.4) and for men, PBW = 50.0 + 0.91 (height in centimeters—152.4). It is well documented that lower tidal volumes (6 mL/kg of predicted body weight) compared to higher tidal volumes (12 mL/kg

mortality in a randomized, clinical trial that analyzed 861 ARDS patients (ARMA trial) [12]. It is crucial to adjust tidal volume to lung size that depends of the height and sex, but more importantly is to adjust the tidal volume to functional lung size that depends on the ARDS severity (lung compliance), sex, height, and chest wall compliance. The patient with severe

of predicted body weight) associated with PEEP levels titrated by a PEEP/FIO<sup>2</sup>

protective ventilation and multiple organ failure are all associated with higher mortality in severe ARDS. However, specific therapeutic aiming to decrease dead space fraction, decrease

levels or even multimodal therapeutic approach to treat multiple organ failure still

those patients.

PaCO<sup>2</sup>

**failure in severe ARDS**

need to be defined and tested [4].

Amato and colleagues [9] analyzed individual data from 3562 patients with ARDS enrolled in nine previously published randomized clinical trials of mechanical ventilation using a multilevel mediation analysis. They observed a strong association between driving pressure and ARDS survival even though all the ventilator settings that were used were lung protective (RR of death: 1.36, 95% CI 1.17–1.58, *P* < 0.001). These observations suggest that tidal volume might be adjusted to the resultant airway driving pressure in addition to the adjustment to the predicted body weight. They also observed that airway driving pressures higher than 15 cm H2 O were associated with increasing rates of mortality in ARDS patients. Recently, Villar and colleagues [10] analyzed the data from two observational studies enclosing 778 patients with moderate and severe ARDS. They assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau inspiratory pressure and airway driving pressure evaluated 24 h after ARDS diagnosis while the patients were ventilated with lung protective ventilation. The authors verified that positive end expiratory pressure and tidal volume that were set according to a protective lung ventilation strategy had no impact on mortality while a plateau pressure higher than 29 cm H<sup>2</sup> O and a driving pressure higher than 19 cm H<sup>2</sup> O were associated with a higher hospital mortality.

As respiratory system driving pressure does not account for variable chest wall compliance or different degrees of intra-abdominal pressures or even more to the presence of inspiratory efforts or asynchrony, esophageal manometry can be used to measure transpulmonary pressure that represents the lungs parenchyma stress during tidal volume ventilation. Recently, Baedorf and colleagues examined the relationships between respiratory system and transpulmonary driving pressure measured at baseline, 5 min and 24 h after PEEP titration and 28-day mortality in 56 ARDS patients. They observed that PEEP titration to target positive end-expiratory transpulmonary pressures resulted in both improved elastance and driving pressures and was associated with improved 28-day mortality.

However, future studies regarding the evaluation of respiratory system and transpulmonary driving pressure in ARDS patients with normal and increased abdominal pressure and various degrees of respiratory system compliance is still needed in order to establish the value of both as a bedside ventilator target as well as a prognosticator of evolution and mortality of those patients.

#### **6. The hole of increased dead space, high PaCO2 and multiple organ failure in severe ARDS**

Increased dead space in the first day of mechanical ventilation, increased PaCO<sup>2</sup> levels with protective ventilation and multiple organ failure are all associated with higher mortality in severe ARDS. However, specific therapeutic aiming to decrease dead space fraction, decrease PaCO<sup>2</sup> levels or even multimodal therapeutic approach to treat multiple organ failure still need to be defined and tested [4].
