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 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