Inhaled Nitric Oxide in Brain Injury

This study will evaluate the changes in respiratory mechanics following traumatic brain injury and determine the effect of inhaled nitric oxide on gas exchange.

Intubation and mechanical ventilation are common treatments in the care of patients with traumatic brain injury (TBI). Intubation allows for airway control and facilitates removal of respiratory secretions. Mechanical ventilation allows control of arterial carbon dioxide to aid in control of intracranial pressure. Recent evidence suggests that lung protective ventilation (tidal volumes of 6 ml/kg of predicted body weight and moderate positive end expiratory pressure) improves outcomes following brain injury and reduces brain-lung cross talk. The treatment of respiratory failure in TBI must balance the need to improve lung function with the negative consequences of increased intrathoracic pressure on mean arterial pressure, intracranial pressure and venous return. Traditional treatment of increasing positive end expiratory (PEEP) and mean airway pressure then, represent competing interests. Methods for improving arterial oxygenation while avoiding negative hemodynamic effects are needed. The impact of head injury on respiratory mechanics has been studied in just a few clinical investigations. (1-3) Of note, the earliest of these noted that the ventilation perfusion (V/Q) matching following TBI was not the result of lung collapse or parenchymal lung disease but secondary to alterations in perfusion. There are three possibilities for this finding: redistribution in regional perfusion, which is partially mediated by the hypothalamus pulmonary microembolism, leading to increased dead space lung surfactant depletion due to excessive sympathetic stimulation and hyperventilation. The introduction of inhaled pulmonary vasodilators such as inhaled nitric oxide or aerosolized epoprostenol offer an opportunity to improve oxygenation in patients with TBI without increasing airway pressures in the face of V/Q inequalities. This study will evaluate the changes in respiratory mechanics following TBI and determine the effect of inhaled nitric oxide on gas exchange.

Following initial non-invasive measurements, patients will be randomized to either an active treatment (inhaled nitric oxide at 30 parts per million) or placebo (nitrogen only). After two hours, measurements will be reassessed. If the patient remains on the mechanical ventilator at 72 hours post-admission, a third set of non-invasive measurements will be taken.

Inhaled nitric oxide at 20 parts per million, administered once during first 36 hours following admission

Inclusion Criteria: Hospital admission with traumatic brain injury (penetrating or blunt) Requirement for mechanical ventilation Glasgow Coma Score > 3 Exclusion Criteria: Brain death Expected survival < 48 hours Air leak (bronchopleural fistula, tracheal injury) Current inspired oxygen concentration (FiO2) > 0.65 Hemodynamic instability (systolic blood pressure < 100 mm Hg, cardiac arrhythmia) Uncontrolled intracranial pressure (> 20 mm Hg) Spinal cord injury with hypotension Severe acute respiratory distress syndrome (ARDS) (PaO2/FiO2 < 100) Chest abbreviated injury score (AIS) > 3 First rib fracture Flail chest

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