Cell Biochem Biophys DOI 10.1007/s12013-014-9911-x
REVIEW PAPER
Current Perspectives for Management of Acute Respiratory Insufficiency in Premature Infants with Acute Respiratory Syndrome Peng Chen • Ying Zhang • Long-Yun Li
Ó Springer Science+Business Media New York 2014
Abstract Current perspectives for management of acute respiratory insufficiency in premature infants with acute respiratory syndrome and the pathology of acute respiratory insufficiency in the preterm infant, including the current therapy modalities on disposition are presented. Since the therapeutical challenge and primary clinical goal are to normalize ventilation ratio and lung perfusion, when respiratory insufficiency occurs, it is very important to introduce the respiratory support as soon possible, in order to reduce development of pulmonary cyanosis and edema, and intrapulmonary or intracardial shunts. A characteristic respiratory instability that reflects through fluctuations in gas exchange and ventilation is often present in premature infants. Adapting the respiratory support on a continuous basis to the infant’s needs is challenging and not always effective. Although a large number of ventilation strategies for the neonate are available, there is a need for additional consensus on management of acute respiratory distress syndrome in pediatric population lately redefined by Berlin definition criteria, in order to efficiently apply various modes of respiratory support in daily pediatrician clinical use. Keywords Respiratory failure Premature infants Acute respiratory distress syndrome Berlin definition
P. Chen L.-Y. Li (&) Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, China e-mail:
[email protected] Y. Zhang Peking University Shenzhen Hospital, Shenzhen 518036, China
Introduction The respiratory failure is a common comorbidity in the group of preterm infants of low (LBW) and extremely low birth weight (ELBW) and usually develops isolated or upon surgical, neurologic, metabolic, or internal concomitant disease state [1]. The overall underlying pathology finding can be highly variable due to stage of pulmonary development. Depending on exact time of delivery and gestation age, clinical finding can be altered depending on degree of surfactant deficiency. Surfactant is not produced in adequate amounts until relatively late in gestation, and thus, the risk of acute respiratory distress syndrome (ARDS) increases with greater prematurity. Prematurity is not only risk factor related to development of ARDS, and respiratory insufficiency correlates with maternal diabetes and multifetal pregnancies.
Clinical Symptoms The clinically defined neonatal respiratory insufficiency is diagnosed if two or more of the following signs are present: respiratory frequency of less than 60 per minute, which transits to bradipnea; tachycardia which progresses to bradicardia; nasal alae widening; dyspnea; cyanosis; and frequent apnea, retraction (inspiratory iugulum retraction and intercostals spaces retraction) (AQ: Please confirm if the phrase, ‘inspiratory jugular retraction’ will be more appropriate with respect to the comtext in lieu of ‘inspiratory iugulum retraction’.)[2]; expiratory grunting with prolonged expiry; cyanosis; irregular breathing according to depth and frequency; apnea; and acid–base status disturbances [2–5].The leading symptoms as stated above
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Cell Biochem Biophys Table 1 Criteria of respiratory insufficiency in premature infants paO2
\6.6 kPa (50 mm Hg) at F1O2 from 0.6 and/or
pCO2
[8–10.6 kPa (60–80 mm Hg)
pH
\7.25
Apnea
[20 per second
include abrupt, labored grunting respirations appearing immediately or within hours after delivery. The lungs become diffusely atelectatic which additionally provokes inflammation and pulmonary edema. It can be simplified that because blood passing through the atelectatic portions of the lung is not oxygenated (forming a right-to-left intrapulmonary shunt), the infant becomes hypoxemic. Overall lung compliance is decreased, thereby increasing the work of breathing. This can lead to the diaphragm and intercostal muscles’s fatigue, and additional retention of CO2 progresses toward development of respiratory acidosis. The premature infant has limited reserves to compensate respiratory insufficiency, while simultaneously its oxygen demands (expressed per kg) are doubled when compared with adult. From this evolves one of the main postulates in therapy of vitally endangered premature that is substitute conditioning which employs the least oxygen demands. This further includes avoidance of any hypothermic state, incubation with neutral temperature, and adding energy-filled substances, perorally or parenterally. The most important thing is to avoid any increased respiratory overload by adequate respiratory therapy. The therapeutical challenge is to normalize the ratio of ventilation and lung perfusion, to reduce as much as possible pulmonary cyanosis and edema as well as intrapulmonary or intracardial shunt evolution. When respiratory insufficiency occurs, it is of importance to introduce as soon possible the respiratory support, oxygen appliance, and/or physical respiratory therapy, and intubation, artificial ventilation as well, in order to achieve the best final results (Table 1). In pathophysiology of respiratory insufficiency when determined, it would be most often due to hypoxic event, and rarely due to primary hypercapnia. If therapy has not been applied promptly, then hypoxia progresses with addition of hypercapnia or vice versa till global respiratory insufficiency develops [6, 7]. Hypercapnic acidosis has traditionally been considered as either not beneficial or harmful in critically ill newborns [8]. The beneficial effects of controlled respiratory acidosis were discovered accidentally as a side effect of reducing the baro/volume trauma and oxygen toxicity related to mechanical ventilation. Injury to the lung was decreased when applying
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low-lung-stretch ventilatory strategies which reduce mechanical trauma and cause mild hypoxemia [3, 9–13]. The respiratory insufficiency categorization is as follows: 1.
Ventilation disturbances
1a. Hypoventilation—leads toward respiratory acidosis which introduces hypercapnia, often with preserved paO2 due to either respiratory center depression (medicamentous when parallel trauma occurred, intracerebral hemorrhage, cerebral edema, tumor, or infection) or peripheral causes such as restrictive states (pneumothorax, hemothorax, pyothorax, and abnormally high diaphragm position due to intra-abdominal tumor), and obstructions (such as aspiration, inflammation, pneumonia, and bronchiolitis). 1b. Hyperventilation is characterized with respiratory alkalosis (low paCO2) developing hypocapnic state (in craniocerebral trauma, or as symptom of hypoxia when cardiac input decreases, or in hypovolemia.) 2.
Normal perfusion disturbances
ventilation
ratio
(p/v
ratio)
The normal p/v ratio is 0.8, and its disturbance leads to hypoxia and lowered paO2. In decreased ventilation, the concomitant pathology is partial or massive atelectatic. When perfusion is decreased, intrapulmonary R-L shunt or cardiac R-L shunt occurs. 3.
4. 5.
Obstacles in oxygen alveolar erythrocytes diffusion are considered to be interconnected with emphysema, alveolar-capillary membrane’s thickening, pulmonary edema, interstitial edema, and interstitial emphysema [14]. Stagnant hypoxia is the state defined as decreased paO2 apparent in cardiac shock. Deficiency of perfusion with concomitant ventilation (pulmonary embolism).
Etiology of neonatal respiratory insufficiency includes processes which can be divided into several groups: 1.
Central respiratory disturbances
The centrally derivated respiratory disturbances include primary post-partal apnea, recidiving apnea, convulsions, brain hemorrhage, meningitis/sepsis, and medicamentous therapy. 2.
Respiratory motor disturbances
Respiratory motor disturbances can be further subdivided into nervous (mediated by spine and medullar damage, paresis of n. phrenicus), myogene (myasthenia gravis, diaphragm relaxation) and thoracic (thoracic atrophy) disturbances.
Cell Biochem Biophys
3.
Airway obstruction
Airway obstruction can be found as nasal obstructions (due to nasal atresion or rhinitis), supralaryngeal obstructions (micrognathia, macroglossia, oral cavity hemangioma), laryngeal obstructions (laryngeal atresia, laryngeal membrane, vocal cord paresis, tumors, hemangiomas, postintubation edema, infective edema, allergic edema), and infralaryngeal obstructions (tracheal atresia or stenosis, tracheoesophageal fistulation, and tracheomalacia. 4.
Alveolar area reduction (restriction)
It has been subdivided into pulmonary restrictions (congenital when pulmonary aplasia is present, lymphangiectasis, pulmonary cysts, and congenital lobar emphysema), acquired (in RDS, meconium aspiration, pneumonia, lung bleeding, Wilson-Mikity Sy., cardial insufficiency with pulmonary edema, transitory neonatal tachypnea (wet lung sy.), and bronchopulmonary dysplasia [15–17]. Pulmonary hypertension sometimes develops despite the absence of alveolar hypoxia and hypercapnia or lung inflammation [10, 17]. It is considered to be the consequence of abnormal pulmonary vascular bedding. Premature infants can be further subdivided in groups according to the degree of muscular layer thickness and the number of pulmonary arteries [18–20]. In infants with hypoplastic lungs, as in oligohydramnios sequence (sometimes secondary to fetal renal dysfunction), patients with alveolar capillary dysplasia may have a similar vascular hypoplasia. These cases may be complicated by increased muscularization of the vessels. 5.
Extrapulmonary restrictions are present in cases of pneumothorax, pneumomediastinum, interstitial emphysema, hemothorax, diaphragmal hernia, after operation of eventration or diaphragmal hernia, congenital heart disease, or tumors.
The most common causes of respiratory insufficiency in neonates are idiopathic respiratory distress syndrome, congenital heart disease, aspiration sy., recidive apneas, central respiratory disturbances, pneumonia, upper or lower respiratory tract malformations, malformations of digestive system in postoperative period, inadequate sedation, analgesia, or anesthesia of mother during delivery. The Pathophysiology of Respiratory Insufficiency Respiratory failure is common condition in the preterm infant. Supports of the infant with oxygen, positive pressure, and assisted ventilation are among the commonest interventions required in neonatal care [21]. Premature infants show a characteristic respiratory instability that is reflected in fluctuations in ventilation and gas exchange. Adapting the respiratory support on a continuous basis to
the infant’s needs is challenging and not always effective. Automatic modes of respiratory support have been developed to address these limitations. Currently, these give us excellent prognosis, reducing mortality rate up to \10 % [22]. If adequate ventilatory support is applied, then surfactant production eventually begins, leading to ARDS resolution within the same week, which is critical in time line. Severe hypoxemia during that period is the source of multiple organs’ failures and lethal outcomes. The goals of therapy are continuous positive airways pressure (CPAP), non-invasive ventilation, various modes of ‘‘conventional’’ ventilation, high-frequency ventilation, and inhaled nitric oxide use. There are proven benefits and limitations of various interventions in use, and areas requiring further investigation should be highlighted. It is clear that respiratory support is life-saving; but there is a lack of good evidence to choose one mode of support preferentially over another [22]. Several prospective trials have been performed which, in general, have failed to demonstrate a significant additional benefit of any newer mode of ventilation over conventional time-cycled pressure-limited ventilation [23]. Before some innovative approaches such as volume-targeted ventilation, pressure support ventilation, and inhaled nitric oxide would be adopted in clinical use in the preterm, further investigations are mandatory. Fast adoption of new protocols and procedures is highly dependent upon ARDS precise diagnosis. ARDS is considered to be a type of diffuse, acute, inflammatory lung injury that leads to increased pulmonary vascular permeability, increased lung weight, and the loss of limited areal of the lung tissue. Kushimoto et al. [24] investigated the empirical relationship between a given ARDS stage and pulmonary microvascular permeability or extravascular lung water (EVLW) content. Their stud evaluated the relationship between extravascular lung water, pulmonary vascular permeability, and the severity categories as defined by the Berlin definition, and they have confirmed the association with severity of ARDS [24]. The Approaching Respiratory Insufficiency as Therapeutic Challenge with Use of Berlin Classification Diagnostic Guidelines The existing evidence seems to be insufficient regarding in human medicine where therapeutic strategies for managing PaCO2 still vary significantly among medical specialists [25]. Specific treatment includes intratracheal administration of surfactant upon endotracheal intubation, which may also be necessary to achieve adequate levels of ventilation and oxygenation. In the case of premature infants with lower O2 demands, when fraction of inspired O2 (FtO2) is \40–50 %, satisfactory response can be provided with supplemental O2 administration alone. Surfactant decreases
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incidences not only of lung comorbidity, such as pneumothorax, interstitial emphysema, bronchopulmonary dysplasia but also of intraventricular hemorrhage. Recently, it has been shown that the Berlin definition of ARDS effectively predicts mortality, the severity of physiological dysfunction, and the associated organ failure [26]. Therefore, it is used to categorize ARDS severity into mild, moderate, and severe ARDS categories which are associated with increased mortality and severity. Once established, the relationship between ARDS severity groups by Berlin categorization and pulmonary microvascular permeability as well as extravascular lung water content, which is the hallmark of lung pathophysiology, are not entirely elucidated. Our take-home message would be that acute respiratory insufficiency must be recognized early in its course to avoid progress of severer consequences. For the moment, the mechanical ventilation is method of choice to treat newborns with severe respiratory failure [27]. Associated risk of lung damage affects the quality of survival which may result in a life-long dependency and places considerable strain on social cost and cost of medical follow-up [28]. The Berlin definition applied in pediatric population is an additional new tool for distinguishing the pulmonary microvascular permeability as well as extravascular lung water content. In addition, there are still a considerable number of infants that die from severe respiratory insufficiency, which demands our further attention, making efforts for improvement mandatory.
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