Pediatric Ards Neuromuscular blockade (PAN) study: Life-threatening acute respiratory failure in children: to breathe or not to breathe spontaneously, that's the question. A multicentre, randomised, double-blind, placebo controlled study.

Paediatric acute respiratory distress syndrome (ARDS) is a manifestation of
severe, life-threatening lung injury. Care for paediatric patients is mainly
supportive and based on what works in adults and personal experiences,
including the use of mechanical ventilation. However, differences in lung
physiology and immunology between (young) children and adults suggests that
adaptation of adult practices into paediatrics may not be justified. A study in
adults with severe ARDS showed that early use of neuromuscular blocking agents
(NMBA) improved 90-day survival and increased time off the ventilator without
increasing muscle weakness. It is unknown if this is also true for paediatric
ARDS. Thus, the next step is to determine the effects of NMBAs on patient
outcome in children with moderate-to-severe ARDS. We hypothesize that NMBAs in
mechanically ventilated children younger than 5 years of age with
moderate-to-severe paediatric ARDS (i.e. oxygenation index > 12 and PEEP > 5
cmH2O despite adequate sedation) reduce respiratory morbidity during follow-up
because they reduce lung and systemic inflammation, improve oxygenation and
improve lung mechanics during the acute phase of illness.

To test the hypothesis that early use of neuromuscular blocking agents for 48
hours in paediatric patients younger than 5 years of age with moderate-to-
severe paediatric acute respiratory distress syndrome will lead to at least a
20% reduction in respiratory morbidity 12 months after discharge from the
paediatric intensive care unit (PICU).

Prospective multicentre randomised double blind placebo controlled trial.

Patients will be randomised to receive either a bolus plus a continuous
infusion of rocuronium bromide 10 mg/ml at a rate of 0.1 ml/kg/hr (compatible
with the recommended dosage of 1 mg/kg/hr (investigational product) or a bolus
plus 0.1 ml/kg/hr isotonic saline (NaCl 0.9%) (control).

The risks associated with this study are minimal based on the following
arguments:
a) patients in the intensive care unit are under constant tight observation, so
any change in vital parameters is noted immediately. Furthermore, patients with
severe lung injury are commonly deeply sedated;
b) blood samples are only taken from an indwelling arterial catheter or central
venous catheter, which are already in place for clinical purposes. Blood
samples for this study will combined as much as possible with routine blood
sampling part of daily clinical care;
c) endotracheal suctioning is routinely performed in mechanically ventilated
patients by nurses taking care of the patients; for this study suctioning
specimens are collected to measure the pulmonary inflammatory response so no
extra suctioning procedures will be performed; and
d) the investigational drug is commonly used in (paediatric) critical care;
hence, there is a good understanding of this drug.

It is important to study the effects of neuromuscular blocking agents on
patient outcome in the paediatric context. There are numerous differences in
lung physiology and immunology between (young) children and adults indicating
that adaptation of adult practices into paediatrics may not be justified.