Supl79-02-b-ingles p65

S156

  

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

Nitric oxide

Nitric oxide is a potent vasodilator that can be

administered via inhalation causing pulmonary vascular

relaxation. Inhaled nitric oxide reaches the alveolus

where it enters into direct contact with the pulmonary

vasculature. During its migration through the wall of the

blood vessel, nitric oxide causes direct relaxation of the

muscular layer, before reaching the vascular lumen.

Nitric oxide is then rapidly deactivated by binding with

hemoglobin, resulting in the formation of methemoglobin

and avoiding the undesirable effect of systemic

vasodilation. The pulmonary vasodilatory effect of nitric

oxide associated with the fact that the target vasculature

is adjacent to the ventilated areas of the lung results in

not only a decrease in pulmonary vascular resistance, but

also in attenuation of ventilation-perfusion mismatch,

thus improving oxygenation. The use of nitric oxide in

newborns with pulmonary hypertension has achieved

great clinical success, reducing morbidity and the need

for extracorporeal support.

45

 However, its use in patients

with ARDS has been disappointing. Despite producing a

transient improvement in oxygenation, this benefit is of

short duration and does not offer any objective gains.

The use of nitric oxide in ARDS does not reduce mortality

or the duration of mechanical ventilation

46

 and cannot

therefore be routinely recommended in clinical practice.

Nitric oxide can be used as a therapy of exception for

temporary rescue of patients with hypoxemia that is

refractory to more conventional interventions.

Corticosteroids

The fact that acute pulmonary damage in ARDS is

primarily the result of an aggressive inflammatory process

has lead intensive care specialists to consider anti-

inflammatories in general, and corticosteroids in

particular, as logical therapeutic alternatives. The use of

corticosteroids, however, does not prevent the

development of ARDS

47

 nor is it beneficial when

employed during the initial phase of its clinical course.

48

Corticosteroids appear to have some benefit when used

during the later stages of the disease, which are marked

by the reorganization of the acute inflammatory

infiltration and fibrosing alveolitis.

49

 Currently, a multi-

center randomized controlled North American study

(ARDS Network) is being conducted to evaluate the

efficacy of high doses of methylprednisolone during the

later phases of ARDS. However, due to the fact that

treatment with high doses of corticosteroids can increase

the risk of secondary infections and other adverse effects,

their routine use in ARDS treatment cannot yet be

recommended. In our clinical practice, we reserve the

use of corticosteroids as a rescue therapy in severe

ARDS cases during the later phase of the disease (third

or fourth week) when there is no progress in reducing the

level of ventilatory support.

Other inflammation control agents

Despite having produced promising results in

experimental models of acute lung injury, the use of non-

steroidal drugs with anti-inflammatory effects, such as

indomethacin, ibuprofen, procysteine, lisofylline and

ketoconazole, have not been shown beneficial in the clinical

arena.

50

 The use of these drugs for the treatment of patients

with ARDS, therefore, cannot be recommended.

Extracorporeal membrane oxygenation (ECMO)

Extracorporeal membrane oxygenation consists of the

use of a complex circuit of vascular cannulae, tubes, pumps,

oxygenator, heat exchanger and monitoring systems used to

provide respiratory support (in the case of veno-venous

ECMO) or cardiorespiratory support (in the case of veno-

arterial ECMO). To date, approximately 25,000 patients

have undergone ECMO throughout the world with an overall

survival rate of approximately 75%. The vast majority of

these patients (17,000) were neonates with refractory

pulmonary hypertension, while the experience in pediatric

and adult cases of ECMO for treatment of ARDS is limited

to approximately 3,000 cases (personal communication,

ECMO Registry of the Extracorporeal Life Support

Organization (ELSO), Ann Arbor, Michigan, November,

2002). Extracorporeal membrane oxygenation reduces the

mortality of newborns with persistent pulmonary

hypertension secondary to meconium aspiration syndrome

(94% survival), but has yielded more modest results in older

children with ARDS (52% survival). Clinical studies of the

use of ECMO or an extracorporeal carbon dioxide

elimination system with adults suffering from ARDS did

not reveal any benefits in terms of reduced mortality.

51

However, the outcome results for ECMO therapy in the

international extracorporeal life support registry for pediatric

patients with ARDS refractory to all other forms of treatment,

and also in our personal practice, strongly suggest that this

technique is of value in selected cases.

Indications for ECMO in ARDS cases are restricted to

patients with the highest degree of acute pulmonary failure

that is potentially reversible, yet unresponsive to all less

invasive conventional or non-conventional treatment

methods. The basic premise for indicating ECMO is that the

death of the patient is presumably imminent without the use

of this technology. During the last 7 years, 22 of these

pediatric patients with extreme respiratory failure

underwent ECMO for treatment of ARDS at the Children’s

Hospital of Buffalo, with a survival rate of 54%. These

results are compatible with those from other centers of

excellence in North America and are a great impediment

to the realization of randomized trials. In common with

us, the majority of centers that utilize this treatment

method consider unethical to allocate patients who are

candidates for ECMO to a control group without

intervention, since such patients have a projected

mortality rate of nearly 100%.

Acute respiratory distress syndrome – Rotta AT 

et alii

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