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

the use of PRVC has been gaining wide acceptance in the

management of patients with ARDS.

Fluid administration

In caring for patients with ARDS, the intensive care

specialist must ponder the quantity and quality of fluids that

will be administered. For rapid intravascular expansion, the

decision on the administration of colloids or crystalloids

depends, to a certain extent, more on the personal convictions

of the individual intensive care specialist than on established

scientific facts. Those who prefer to give colloids justify the

practice by the fact that these substances are capable of

producing greater intravascular expansion per unit of volume,

remain longer within the intravascular space and increase

colloid osmotic pressure. Those who choose crystalloids

do so because these are cheaper, more readily available,

are capable of promoting intravascular expansion

equivalent to colloids (when infused volumes are

adjusted) and because they do not increase oncotic

pressure in the pulmonary interstitium should they

extravasate from the capillaries, as can occur with

colloids. Controlled clinical studies are inconclusive on

the superiority of colloids or crystalloids. Therefore, the

choice of fluids for rapid intravascular expansion should

be based on the patient’s needs at any given moment,

taking into account the type of loss that has occurred, the

urgency to resuscitate and the availability of fluids, in

addition to plasma colloid osmotic pressure.

The amount of fluids administered to patients with

ARDS is also the subject of debate. There is no question

that patients in shock or with severe hypovolemia, both

risk factors for ARDS, should be aggressively

resuscitated, generally with infused volumes that exceed

60 ml/kg during the first hour, since this practice reduces

mortality and is not associated with an increased incidence

of ARDS.

25

 Once hemodynamic stability is achieved in

the patient with ARDS, the intensive care specialist

should concentrate efforts on minimizing the capillary

leak and pulmonary edema accumulation that occur in

ARDS. Studies in animal models of acute lung injury

indicate that the fluid accumulation in the lung can be

attenuated by reducing left atrial pressure.

26

 This strategy

of limiting fluid administration is also supported by

some clinical studies of patients with ARDS.

27,28

 The

North American study group involving 24 hospitals

(ARDS Network) organized for the study of ARDS is

currently conducting a controlled multi-center,

randomized study of “conservative” versus “liberal”

fluid administration. Until the results of this study become

available, a sensible recommendation is to maintain

intravascular volume at the lowest level that permits the

maintenance of adequate systemic perfusion, assessed

by renal and cardiac functions and by the acid-base

balance.

Non-conventional ventilation

High frequency ventilation (HFV)

Mechanical ventilation techniques that employ supra-

physiologic frequencies, generally between 60 and 900

cycles per minute, are collectively known as HFV. Various

types of HFV are available, although only high frequency

positive pressure ventilation (HFPPV), high frequency jet

ventilation (HFJV) and high frequency oscillatory ventilation

(HFOF) have gained significant penetration into clinical

practice. Clinical studies of HFPPV and HFJV compared

with conventional ventilation were disappointing and

resulted in the virtual abandonment of these techniques for

the management of patients with ARDS.

29

 The use of

Figure 4 - Comparison of dynamic airway pressure

waveforms during pressure-controlled (a) and

volume controlled (b) ventilation

a

b

Time

Pressure

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HFOV, however, is strongly supported by studies of

experimental ARDS models.

17,30,31

 and has sufficient

clinical evidence to justify its use under selected

circumstances.

32-34

In HFOV, tidal volumes that approximate dead space

volume are actively pushed into and pulled out of the

airway at a frequency of between 3 and 15 hertz (180 to

900 cycles per minute) by means of a piston or diaphragm.

The proposed advantage of HFOV is that, due to the

minute tidal volume of each cycle, the method is capable

of ventilating patients with ARDS within a “Safety Zone”

that avoids both alveolar overinflation during inspiration

and cyclical closure and re-opening of the alveoli during

expiration (Figure 2). Oxygenation and ventilation are

controlled independently during HFOV. Controlling the

mean airway pressure determines the state of pulmonary

inflation and, consequently, oxygenation. Controlling

the amplitude of oscillation indirectly determines the

tidal volume of each cycle and, consequently, the efficacy

of ventilation (CO

2

 elimination). As such, HFOV is ideal

in situations when the patient with ARDS has worsening

pulmonary compliance with hypoxemia, requiring a

reduction in the Vt of conventional ventilation in order to

avoid elevated peak inspiratory pressures, which leads to

significant respiratory acidosis. The realization that

HFOV can favorably influence the pulmonary

inflammatory milieu in experimental models

17,31,35

 as

well as reduce the incidence of chronic lung disease

32,34

has been responsible for the enthusiasm about this method

and for its increasingly early deployment in patients with

ARDS. The use of HFOV in pediatric patients with

ARDS requires deep sedation and neuromuscular

relaxation, since spontaneous respiratory movements

interfere with gas flow mechanics in this modality.

Non-invasive ventilation

The application of non-invasive positive pressure

(CPAP or BiPAP) in patients with ARDS is capable of

attenuating, albeit temporarily, the reduction in residual

functional capacity responsible for the progressive

hypoxemia that is characteristic of this pathology. The

use of CPAP results in a transient improvement in

oxygenation, yet it is not associated with reductions in

the need for intubation, length of hospital stay or mortality

of patients with ARDS.

10

 The use of CPAP for ARDS is

also associated with an increased incidence of adverse

effects.

10

 As such, the use of CPAP in the prophylaxis or

treatment of patients with ARDS is not recommended.

Partial liquid ventilation

Partial liquid ventilation (PLV) is a technique that

employs perfluorochemical substances capable of

dissolving large quantities of oxygen and carbon dioxide.

In PLV, the lung is filled with a liquid perfluorocarbon

via the endotracheal route so as to occupy the functional

residual capacity, while volumes of gas are introduced

through a conventional ventilator during each inspiratory

cycle.

36

 The potential advantage of PLV in ARDS stems

from the fact that when the lung is occupied by liquid it

has a uniform surface tension, in contrast to the

heterogeneous surface tension typical of ARDS. This

occurs because the perfluorocarbon forms a liquid-liquid

interface at the alveolar surface, in contrast to the liquid-

gas interface found in conventional ventilation. A

medical-grade perfluorocarbon called perflubron (C8-

F17-Br1) has been successfully tested in the treatment of

experimental acute lung injury. We now know that

perflubron, as well as other perfluorocarbons that were

considered biologically inert, have anti-inflammatory

biological effects and protect cellular components against

oxidative damage.

37-41

 However, the enthusiasm for

PLV in the laboratory has not been repeated in the

clinical arena. Controlled studies of children and adults

with ARDS and acute lung injury have not demonstrated

PLV to be superior to protective conventional

ventilation.

42

 Further studies are necessary to test the

impact of this method in specific clinical situations, such

as progressive pulmonary recruitment (liquid PEEP) and

intrapulmonary drug administration or viral vectors for

genetic therapy. This treatment is not currently available

for use outside of the research laboratory environment

and cannot be recommended for the treatment of ARDS.

Drug-based therapies

Surfactant replacement

The success of surfactant therapy with premature

newborns, associated with the fact that the surfactant

system is dysfunctional in patients with ARDS, led

intensive care specialists to speculate on a possible role

for this substance in the treatment of this syndrome.

However, the use of surfactant in adult patients has not

been shown effective at improving oxygenation,

shortening duration of mechanical ventilation or reducing

mortality in a controlled clinical study.

43

 Possible

explanations for this include the administration method

employed (aerosol), which results in less than 5% of the

dose, as well as the type of surfactant used (a phospholipid

preparation without surfactant proteins). New surfactant

preparations extracted from bovine lungs that contain

phospholipids, neutral lipids and hydrophobic surfactant

proteins types B and C are considered to be more effective

and are being tested in patients with ARDS for

administration via endotracheal tube.

44

 Until definitive

studies are available, the routine use of surfactants in

patients with ARDS cannot be recommended, being

reserved for non-routine use in special situations when

recruitment of lung segments cannot be achieved with

more conventional methods. Even in these situations, the

use of surfactants in ARDS is questionable.

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