High-frequency ventilation augments the effect of inhaled nitric oxide in persistent pulmonary hypertension of the newborn

Abstract

aaHigh-frequency ventilation (HFV) is widely used for rescue treatment of hypoxaemic neonates and premature infants [1]. Although its role as a first-line mode of ventilation has not been established, it is often applied in newborns with respiratory failure, who cannot be successfully managed with conventional mechanical ventilation (CMV). The results of recent studies investigating the theoretically diminished baro-and volutrauma remain equivocal. Nonetheless there is evidence for a decreased secretion of inflammatory mediators [2] and a reduced amount of lung oedema [3] using high-frequency oscillatory ventilation (HFOV) with or without additional application of exogenous surfactant.Inhaled nitric oxide (iNO) as a treatment for neonatal pulmonary hypertension has been in use for the past few years, both in premature infants and in term neonates [4][5][6][7][8][9]. It is worth noting that the first published application of iNO in a premature infant, and the subsequent improvement of oxygenation, occurred during HFOV [10]. Although still an experimental treatment, NO inhalation plays an important therapeutic role in severe hypoxaemia of the newborn due mainly to extrapulmonary shunting [11,12].Recently, a randomized, multicentre trial showed that the combination of iNO and HFOV was superior in term neonates, as compared to either treatment alone [13]. We report a similar experience in a full-term neonate, but also in a premature infant of 29 weeks of gestation. Case 1The term infant was delivered by caesarean section because of maternal hypertension. There was no maternal history of infection. The infant was male and had a birth weight of 3,810 g and Apgar 9,10,10 (1',5',10'); he became symptomatic at the age of 15 min with intercostal retractions and grunting. At that stage, capillary blood gases were: pH 7.23, capillary carbon dioxide tension (Pc,CO 2 ) 8.0 kPa (60 mmHg), capillary oxygen tension (Pc,O 2 ) 4.0 kPa (30 mmHg) in combination with an increasing inspiratory oxygen fraction (FI,O 2 ). At the age of 2 h the neonatal transport team was called, which arrived about 1 h later. The infant was intubated and ventilated because of persistent cyanosis, antibiotic treatment was started and he was transferred to our neonatal intensive care unit. Upon arrival, bovine surfactant (100 mg·kg -1 ) was applied; in order to achieve adequate oxygenation, peak inspiratory pressures (PIPs) up to 4.6 kPa were required (positive endexpiratory pressure (PEEP) 0.5 kPa, rate 70 breaths·min -1 , inspiratory time 0.35 s, mean airway pressure (MAP) 1.8 kPa, FI,O 2 1.0). After approximately 6 h a sudden deterioration of oxygenation and arterial blood pressure occurred, caused by a pneumopericard, which was relieved by drainage. During this event, profound hypoxia occurred for about 15 min, the continuously recorded arterial oxygen saturation (Sa,O 2 ) (measured by pulsoximetry) was approximately 20%. Following drainage of the pneumopericard We report two cases of newborn infants with profound hypoxaemia, who did not respond with ...

Acute oxygenation response to inhaled nitric oxide when combined with high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome*

“…In humans, published data evaluating the combined effect of HFOV and INO are limited to the neonatal literature (22,23). In a multicenter study, 205 hypoxemic neonates with persistent pulmonary hypertension of the newborn, due to respiratory distress syndrome, meconium aspiration, idiopathic persistent pulmonary hypertension of the newborn, or congenital diaphragmatic hernia, were randomized to CV and INO, or HFOV alone (23).…”

“…Support for this concept is in recent studies demonstrating that some INO nonresponders become responsive to INO with PEEPinduced alveolar recruitment (3,6,7). In animal models (8) and in persistent pulmonary hypertension of the newborn (9), studies have shown that lung recruitment strategies such as HFOV (10) and partial liquid ventilation (8,11) augment both the degree of oxygenation improvement and the percentage of subjects responding to INO. In adults with ARDS, prone positioning has also been combined with INO (12,13). The mechanisms of oxygenation improvement during prone positioning are complex (14,15); however, one of the proposed mechanisms is an increase in functional residual capacity.…”

Current Applications of Therapeutic Gases in Neonatal Intensive Care

“…NO administration does not require specific devices, but studies both in animals [5] and in newborns [6] reported better results applying a correct pulmonary inflation strategy, as achieved during High Frequency Oscillatory Ventilation (HFOV). However in neonates treated with conventional mechanical ventilation, the NO concentration does not change during the fluctuation of the inspiratory flow, as described with adults [7].…”

Persistent Pulmonary Hypertension of the Newborn: Therapeutical Approach

“…The favourable response to iNO is dependent on the degree of lung expansion and is more readily achieved by the use of high-frequency ventilation than conventional ventilation [67].…”