Supl79-02-b-ingles p65

Jornal de Pediatria - Vol.79, Supl.2, 2003 

 S151

The administration of oxygen, while simple, is not free

from adverse effects. Continuous exposure to high

concentrations of oxygen (FiO

2

 > 0.6) is capable of causing

pulmonary injury, even in the absence of a pre-existing

lesion.

7

 Pulmonary injury due to oxygen toxicity is the

result of free radicals and reactive oxygen species that are

spontaneously generated in hyperoxic environments or

from the activation of neutrophils and alveolar

macrophages.

8,9

 The normal lung deals with oxidative

insults by means of a series of enzymes (superoxide

dismutase, glutathione peroxidase, glutathione reductase,

catalase) or antioxidants (vitamins C and E, albumin, etc.),

and is capable of tolerating elevated oxygen concentrations

for a number of days. However, an injured lung exposed to

moderate concentrations of oxygen (which would not be

harmful to a normal lung) can further aggravate pulmonary

tissue damage even when the exposure is limited to just a

few hours.

8

 This phenomenon occurs, presumably, due to

an imbalance between oxidative stimuli and antioxidant

protective mechanisms found in acute lung injury states.

Mechanical ventilation

Mechanical ventilation remains the primary support

technique for ARDS and is indicated in the vast majority of

cases.

10

 Nonetheless, the indications for mechanical

ventilation in patients with ARDS are, to a certain extent,

vague, based on clinical findings (dyspnea, tachypnea, use

and fatigue of accessory muscles, diaphoresis, poor

perfusion, etc.), laboratory findings (acidosis, hypoxemia,

hypercapnia) and radiological findings (worsening alveolar

infiltrates). An attempt at making the criteria for the

institution of mechanical ventilation for ARDS more

objective is the so-called “rule of 50s”, in which a PaO

2

 < 50

torr and a PaCO

2

 > 50 torr with a FiO

2

 of 50% characterize

patients likely to require ventilatory support. These criteria,

however, identify patients in extremely severe disease states

with impending respiratory failure. One of the key points in

the treatment of ARDS is the early identification of patients

with respiratory involvement so that mechanical ventilation

can be initiated before they reach an extreme state of

respiratory failure.

The heterogeneous distribution of lung disease in patients

with ARDS makes mechanical ventilation a challenge to the

intensive care specialist. In typical ARDS, gravitationally-

dependent lung regions exhibit dense alveolar and interstitial

inflammatory infiltrates, edema, cellular debris, atelectasis

and consolidation, while non-dependant regions are

relatively spared (Figure 1).

11

 In a healthy lung with

homogeneous surface tension, tidal volume is evenly

distributed among the various lung segments. In patients

with ARDS, however, the tidal volume follows the path of

least impediment, with a tendency to overdistend the more

compliant alveoli (non-dependent) while failing to recruit

the less compliant alveoli in the dependent areas. In addition

to being heterogeneous, lung pathology in ARDS is also

dynamic,

12

 as areas with relatively adequate compliance

can become poorly compliant in a matter of hours, as the

syndrome evolves rapidly.

Mechanical ventilation for ARDS is much more than a

mere support modality used to buy time until resolution of

the lung disease process. We now know that the choice of

ventilation strategy is capable of influencing the progression

of the lung disease, with more favorable outcomes resulting

from protective strategies. Similarly, non-protective

ventilation strategies are associated with less favorable

physiological outcomes and increased mortality.

5,13-15

Figure 1 - a) Computerized axial tomography of an experimental

ARDS model (swine) showing the heterogeneous

distribution of lung disease. The gravitationally non-

dependent lung region (white arrow) exhibits a

relatively normal aspect, while the dependent lung

region (black arrow) exhibits greater involvement.

Histologic analysis of another animal model of ARDS

(rabbits) also shows the heterogeneous distribution

of this pathology, with less evidence of inflammation

and tissue injury in the non-dependent region (b) in

contrast with the dependent region (c). The use of

an objective pulmonary injury score in this same

model (d) confirms the heterogenous distribution

of tissue injury

Injury

score

Dependent

Non-

dependent

16

14

12

10

8

6

4

2

0

d

c

b

a

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Jornal de Pediatria - Vol.79, Supl.2, 2003

Tidal volume (Vt)

The use of an inadequately high Vt in experimental

models is capable of promoting pulmonary injury even in

healthy lungs.

16

 In experimental ARDS models, a Vt that

has traditionally been considered adequate, such as 10 ml/kg,

has been associated with progression and worsening of the

pulmonary injury.

17

 This occurs because, in low pulmonary

compliance states, the introduction of moderate or high Vt

can lead to alveolar overdistension, marked by the upper

inflection point on the volume-static pressure relationship

curve (Figure 2), resulting in the so-called “volutrauma”.

Based on this principle, Amato and colleagues have

demonstrated significantly reduced 28-day mortality in

ARDS patients treated with an open lung strategy consisting

of a Vt of less than 6 ml/kg and PEEP set above the lower

inflection point. However, two other studies, employing

reduced Vt only

18,19

 failed to show any benefit from this

strategy in patients with ARDS. More recently, a North

American multi-center study involving 861 patients with

ARDS

15

 showed a 22% reduction in mortality among

patients treated with reduced Vt (6 ml/kg) in comparison

with traditional Vt (12 ml/kg). The discrepancies between

results of the various multi-center studies are related to

significant methodologic variations, such as different Vt

values employed for the intervention and control groups

(Figure 3). Only studies with a sufficient difference in Vt

between the reduced volume and the control groups

5,15

yielded positive results.

To this date, no clinical studies have tested the hypothesis

that reduced Vt would be beneficial in the pediatric

population. However, considering that the recommendation

to use reduced Vt has a strong physiological, experimental

and clinical support (in adults), pediatric patients with

ARDS should be given mechanical ventilation with a Vt

equal to or less than 6 ml/kg until data specific to this

population become available.

Positive end-expiratory pressure (PEEP)

In ARDS, alveoli in the dependent lung regions exhibit

greatly reduced compliance in comparison with non-

dependent alveoli. As such, during every expiration the

more dependent alveoli reach a critical closing volume,

which results in alveolar collapse. This is followed by

reopening of these collapsed alveoli during inspiration. The

cyclical repetition of alveolar collapse and re-opening

generates shearing forces capable of causing tissue damage

(atelectrauma). The use PEEP is primarily aimed at avoiding

the collapse of the less compliant alveoli at the end of

expiration. Excessive use of PEEP increases the risk of

pneumothorax, generates hyperinflation of certain

pulmonary segments and can cause adverse hemodynamic

effects by increasing intra-thoracic pressure and thus

reducing venous return (pre-load). However, the application

of inadequately low PEEP levels during mechanical

ventilation provokes cyclic alveolar collapse and re-opening,

resulting in atelectrauma.

The use of adequate levels of PEEP that target sufficient

lung volume maintenance during is associated with favorable

physiological outcomes.

13,16,17

 As has been mentioned

above, Amato and colleagues

5

 have demonstrated a

reduction in 28-day mortality in patients ventilated with a

Vt lower than 6 ml/kg and PEEP level set above the lower

inflection point. It is impossible to discern whether the

observed effects

5

 are attributable to the limited Vt, the use

Figure 2 - Static pressure-volume relationship of the respiratory

system in an animal model of ARDS (rabbits). The

arrow indicates the lower inflection point

50

40

30

20

10

0

0

“Safety” zone

Volutrauma zone

Atelectrauma zone

10

20

Pressure (cm H O)

2

Volume

(ml)

30

40

50

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