肺源性与肺外源性急性呼吸窘迫综合征呼吸力学的异同及机械通气策略

急性呼吸窘迫综合征(ARDS)按其病因可分为肺源性ARDS和肺外源性ARDS.肺源性ARDS早期多为肺泡损害,而肺外源性ARDS多为间质性肺水肿.肺源性ARDS患儿肺顺应性降低,而肺外源性ARDS由于腹腔内压增高其胸壁顺应性更低.肺外源性ARDS中应用呼气末正压、肺复张手法及俯卧位通气效果更好,而两者的小潮气量通气效果相似.     

肺源性与肺外源性急性呼吸窘迫综合征呼吸力学的异同及机械通气策略

急性呼吸窘迫综合征(ARDS)按其病因可分为肺源性ARDS和肺外源性ARDS.肺源性ARDS早期多为肺泡损害,而肺外源性ARDS多为间质性肺水肿.肺源性ARDS患儿肺顺应性降低,而肺外源性ARDS由于腹腔内压增高其胸壁顺应性更低.肺外源性ARDS中应用呼气末正压、肺复张手法及俯卧位通气效果更好,而两者的小潮气量通气效果相似.     

肺源性与肺外源性急性呼吸窘迫综合征呼吸力学的异同及机械通气策略

急性呼吸窘迫综合征(ARDS)按其病因可分为肺源性ARDS和肺外源性ARDS.肺源性ARDS早期多为肺泡损害,而肺外源性ARDS多为间质性肺水肿.肺源性ARDS患儿肺顺应性降低,而肺外源性ARDS由于腹腔内压增高其胸壁顺应性更低.肺外源性ARDS中应用呼气末正压、肺复张手法及俯卧位通气效果更好,而两者的小潮气量通气效果相似.     

Ventilation in special situations. Mechanical ventilation in acute respiratory distress syndrome/acute pulmonary lesion

Acute respiratory distress syndrome (ARDS), which was first described by Ashbaugh in 1967, consists of acute hypoxemic respiratory failure (PaO2/FiO2< or =200) associated with bilateral infiltrates on the chest radiograph caused by noncardiac diffuse pulmonary edema. Although ARDS is of multiple etiology, pulmonary or extrapulmonary injury can produce systemic inflammatory response that perpetuates lung disturbances once the initial cause has been eliminated. Most patients with ARDS require mechanical ventilation. Currently, the old standard is conventional ventilation optimized to protect against ventilator-associated lung injury. Other mechanical ventilation strategies such as high-frequency oscillatory ventilation, which is also based on alveolar recruitment and adequate lung volume, can be useful alternatives. In this review, the level of evidence for other therapies, such as prone positioning, nitric oxide and prostacyclin inhalation, exogenous surfactant, and extracorporeal vital support techniques are also analyzed.     

Maturation of respiratory responses to graded hypoxia in rabbits

The respiratory effects of graded hypoxia were determined in 8 rabbits on postnatal days 1, 6 and 21. Ventilation was measured in the unanesthetized state by plethysmography. Graded hypoxia was produced by reducing the fraction of inspired O2 to 0.15 (mild hypoxia) for 15 min and then lowering it further to 0.10 (moderate hypoxia) for another 15 min. Mild hypoxia initially stimulated breathing to the same extent in all 3 groups; however, with moderate hypoxia, the percent increase in ventilation was greater for older rabbits. The rise in ventilation was due to an increase in tidal volume and frequency in 1- and 21-day-old rabbits, and it was almost entirely the result of changes in frequency in 6-day-old rabbits. After 2-3 min of hypoxia (mild or moderate), a decline in ventilation was observed in all 3 groups. This reduction of respiration was greater in younger animals and with moderate hypoxia. Decreases in frequency and tidal volume contributed significantly to this fall in ventilation for 1- and 2-day-old rabbits. However, the fall in ventilation for 6-day-old pups occurred almost entirely by changes in tidal volume. It is concluded that the magnitude of phase 1 (increased ventilation) and phase 2 (decreased ventilation) responses to hypoxia depend upon the level of hypoxia and the age of the rabbit.     

Transient left myocardial dysfunction: a cause of neonatal hypoxemia]

Refractory hypoxemia in the newborn requires an accurate diagnostic investigation for an optimal and prompt management. CASE REPORT: After a short delivery, a post-term newborn developed a severe hypoxemia with patchy pulmonary alveolar opacities and systolic right-to-left extrapulmonary shunting through the ductus arteriosus. Echocardiography ruled out a cardiac malformation and showed dilated left atrium with left-to-right shunting by the ovale foramen due to left ventricular dysfunction. Inotropic support associated with mechanical ventilation allowed a rapid improvement. CONCLUSION: A pathophysiological analysis is needed in case of severe neonatal hypoxemia. Doppler ultrasound is a non invasive and rapid method allowing the adjustment of the therapeutic strategy.     

Recent advances in hyaline membrane disease

Survival of infants with HMD has improved remarkably in the last decade. This has resulted from improved methods of diagnosis, which enables clinicians to recognize infection, the patent ductus, and the presence of pulmonary hypertension complicating HMD; from improved methods of ventilation, which result in a lower incidence of acute and chronic complications; and from a reduced incidence of pulmonary and extrapulmonary complications, such as bronchopulmonary dysplasia and retrolental fibroplasia. These advances arise from a deep understanding of pulmonary and metabolic physiology of the newborn infant with respiratory distress. Only an approach firmly rooted in an understanding of physiology, pharmacology, and biochemistry can be completely successful in the therapy of these infants.     

Congenital chylothorax with hydrops: postnatal care and outcome following antenatal diagnosis

We consecutively managed 25 cases of fetal chylothorax with hydrops (pleuroamniotic shunting in 20/25 cases). Three of the 16 liveborn infants died before day 5 from malformations (n = 1) or complications of antenatal origin (n = 2). Eleven of the 13 survivors were treated in our unit. Four infants whose chylothorax had resolved before birth following antenatal shunting were delivered at term, and had no respiratory disease. Seven infants, whose chylothorax persisted, were delivered prematurely and required intensive respiratory care (with mechanical ventilation for a median duration of 34 days). The 11 infants were maintained on total parenteral nutrition for a median duration of 31 days. They were discharged home after complete clinical recovery at a median age of 64 days. Antenatal pleuroamniotic shunting may improve the prognosis of congenital chylothorax with hydrops. Chylothorax persisting at birth resolves progressively with medical management. Congenital chylothorax, critical care, non-immunologic fetal hydrops, pleuroamnotic shunting, preterm newborn     

Dynamic changes in glottal resistance during exposure to severe hypoxia in neonatal rats in situ

The neural control of respiratory airflow via the vocal fold is characterized by inspiratory abduction and postinspiratory (early expiratory) adduction causing decreases and increases in glottal resistance, respectively. The postinspiratory increase in glottal resistance plays a major role in braking the speed of expiratory airflow, to act against the high recoil pressure of the neonatal rat lung. In the present study, we investigated changes in upper airway patency during severe hypoxia in neonatal rats. We measured dynamic changes in subglottal pressure during normoxic and hypoxic conditions in an arterially perfused brainstem preparation in which we could control gas tensions accurately. Initially, hypoxia (5% O(2), 5% CO(2), and 90% nitrogen) produced an excitatory response in phrenic nerve activity accompanied by augmentation of both inspiratory-related glottal dilation and postinspiratory glottal constriction. Later, during the early stages of hypoxia-induced respiratory depression and initiation of gasping, we observed a massive reduction of the respiratory modulation of glottal resistance. In most preparations, this was transient and replaced by a paradoxic inspiratory-related glottal constriction. We propose that during severe hypoxia in the in situ preparation, paradoxic inspiratory glottal constriction can be observed during gasping, and this may impair ventilation despite the persistence of rhythmic contractions of the respiratory muscles. The latter is of clinical interest, because this may relate to the finding of cot death victims who died as a result of upper airway obstruction but without apparent apnea or rebreathing.     

Aminophylline reduces hypoxic ventilatory depression: possible role of adenosine

Newborn infants and animals typically exhibit a paradoxical ventilatory response to hypoxia. The depressive phase of the response has not been adequately explained. It has been suggested that hypoxia may cause the release of inhibitory neuromodulators which depress ventilation. We have postulated that the nucleoside, adenosine, may be involved because 1) it is rapidly released during hypoxia, 2) it depresses ventilation, and 3) theophylline, a competitive inhibitor, has successfully been used to treat apnea of prematurity. Herein we describe the effects of aminophylline on ventilation during hypoxia in the spontaneously breathing newborn piglet administered both rapidly after ventilatory depression has occurred (bolus) and before the onset of hypoxia (pretreatment). Ten percent oxygen breathing produced a typical biphasic ventilatory response. The decrease in minute ventilation was caused by a decrease in both tidal volume and respiratory frequency. The bolus administration of aminophylline reversed the depression in minute ventilation (p less than 0.001) by increasing tidal volume (p less than 0.002). Pretreatment with aminophylline decreased the amount of ventilatory depression (p less than 0.05) by preventing a decrease in respiratory frequency. We conclude that aminophylline, an adenosine antagonist, reduces the decrease in ventilation which occurs during hypoxia in the newborn. We speculate that adenosine may play a role in hypoxic ventilatory depression and respiratory control in the newborn.     

Effect of inhaled nitric oxide on intrapulmonary right-to-left-shunting in two rabbit models of saline lavage induced surfactant deficiency and meconium instillation

Marked hypoxia secondary to intrapulmonary right-to-left shunting is a characteristic of respiratory failure in human neonates and can sometimes be complicated by additional extrapulmonary right-to-left shunting. To investigate the effect of inhaled nitric oxide (iNO) on intrapulmonary shunting, two typical pulmonary diseases of the newborn (respiratory distress syndrome and meconium aspiration) were reproduced in 32 mechanically ventilated rabbits weighing approximately 2 kg each. After tracheotomy, catheters were inserted into a jugular vein, a carotid artery and the right ventricle (to measure systolic right ventricular pressure [SRVP] and mixed venous oxygen content for calculation of shunt by Fick equation). Repeated airway lavages (LAV) with normal saline or repeated instillations of a suspension of human meconium (MEC) were continued until both the a/A-ratio was ≤0.14 and a peak inspiratory pressure ≥22 mbar was needed to keep the tidal volume constant at 10 ml/kg of body weight. Measurements of shunt, SRVP, systolic systemic pressure, physiological dead space, tidal volume and a ventilation index were performed before and after completion of lung damage and at 20 and 60 min after administering iNO at 80 ppm. Four groups of rabbits were studied (n = 8 in each group): LAV control and intervention, Mec control and intervention. 60 min after starting iNO, there was a decrease in shunt (LAV: 67.6% ± [SD] 11.3% vs 56.2 ± 16.4, P = 0.05; MEC: 52.6 ± 6.3 vs 44.3 ± 8.3, P < 0.05), in SRVP (LAV: 29.7 mmHg ± 10.1 mmHg vs 20.0 ± 8.2, P < 0.01; MEC: 25.1 ± 4.4 vs 22.3 ± 5.0, P = 0.46) and in dead space (% of tidal volume, LAV: 32.7% ± 10.5% vs 25.9 ± 10.1, P < 0.01; MEC: 26.1 ± 16.6 vs 18.9 ± 10.1, P = 0.05). These results demonstrate that iNO decreases intrapulmonary shunt (as well as SRVP and dead space). We suggest that iNO may be beneficial in human newborns with severe respiratory failure even if no extrapulmonary shunting via ductus or foramen ovale is apparent. Received: 18 March 1997 and revised form 6 September 1997 / Accepted: 7 September 1997     

Complications and survival rate in preterm infants and neonates treated with mechanical ventilation (author's transl)]

Between January 1972 and December 1976 201 preterm infants and neonates were treated with mechanical ventilation. These children were classified into 6 groups according to the indications for mechanical ventilation: P = respiratory failure caused by pulmonary disease; Z-P = respiratory failure caused by cerebral disturbance with simultaneous respiratory disease; Z = respiratory failure caused by cerebral disturbance; C = respiratory failure caused by cardiac disease; SCH = respiratory failure through shock; M = respiratory failure caused by mechanical disturbance; Bronchopulmonary complications developed in 70% of the survivors and in 60% of the fatalities. The most serious bronchopulmonary complications were infections which occured with similar frequency in all indication groups as late-onset complications, and air-leaks which occured as early complications. The latter complication was significantly higher (38%) in the first than in the other groups. The most serious extrapulmonary complications were seizures, intracerebral hemorrhages and septicemia. 71 of the 201 patients survived. There was a significant increase in the survival rate from 21.2% in 1972-1973 to 43% in 1974-1976. The survival rates differed significantly within the indication groups. The best result was found in the p-group followed by the Z-group. The highest mortality rate was found in the SCH and C-group.     

Assisted ventilation in infants with meconium aspiration syndrome.

In a retrospective analysis of infants born with meconium staining over an 18-month period at Cook County Hospital, 32 infants met two of the three criteria for the diagnosis of meconium aspiration syndrome: (1) history of meconium in the oropharynx or trachea; (2) clinical evidence of respiratory distress; and (3) x-ray evidence of aspiration pneumonia. Seventeen infants developed respiratory failure; nine of these infants died. One infant without respiratory failure died of sepsis. Analysis of sequential arterial blood pH and gas tension showed that nonsurviving infants had persistently high PCO2 and A-a gradient in spite of initiation of assisted ventilation. These changes seem to be related to severe right-to-left shunting and ventilation perfusion abnormalities. The data further suggest that asphyxia and acidosis occur well before the infant is born and that intrapartum monitoring to recognize fetal asphyxia may help in improving morbidity and mortality from meconium aspiration syndrome.     

Prenatal starvation retards development of the ventilatory response to hypoxia in newborn guinea pigs

Prenatal starvation causes pulmonary hypoplasia in newborn guinea pigs, and is associated with postnatal cyanosis, hypothermia, and respiratory failure. To determine the effects of such starvation on ventilation, neonates from litters either fed ad libitum throughout gestation (control) or given 50% rations in the last trimester of pregnancy (starved) were studied at 29 degrees C by plethysmography in 21, 11, and 5% O2. After 15 min (steady-state) in 11% and then 5% O2, 13 of 14 controls (mean = 95 g) sustained increases in weight-specific minute ventilation of 46 and 75% compared to values in air (p less than 0.01), due to increases in respiratory frequency. Seven of 11 starved neonates (mean = 76 g) also sustained increases in respiratory frequency and weight-specific minute ventilation in 11 and 5% O2 similar in magnitude to those of the normal controls, although at higher weight-specific tidal volumes. One abnormal control (85 g) and four starved neonates (mean = 70 g) hyperventilated in air, did not respond to 11% O2, and then hypoventilated in 5% O2 due to a reduced weight-specific tidal volume. Neonates with normal ventilatory patterns did not alter weight-specific minute ventilation in 100% O2 and did not show a biphasic response in acute (1-5 min) exposures to moderate hypoxia, as noted for newborn of other species. Thus, hypoxia identified those starved neonates in which pulmonary immaturity or other starvation-induced pathologies necessitated a maximal ventilatory effect in air. The sustainable hyperventilation among normal guinea pigs during hypoxia emphasizes the precocial development in this species at birth, which may be compromised by intrauterine starvation.     

Management of the upper airway and congenital cystic lung diseases in neonates

Congenital upper airway obstruction can pose difficult problems immediately after birth. Newer strategies to maintain the airway in such situations include pharyngeal ventilation, the laryngeal mask airway and flexible fibreoptic intubation. These methods have decreased the potential for malformations such as Pierre Robin sequence to cause perinatal hypoxia. The most devastating upper airway problem is total obstruction at the supraglottic, glottic or tracheal level without tracheo-oesophageal communication. This can usually be detected prenatally and its management may include the use of the EXIT (ex-utero intrapartum) procedure. Congenital space-occupying lesions of the lung can be detected prenatally with ultrasound. Their management must be individualised, as their pre- and postnatal development is difficult to predict. Very large lesions can lead to lung hypoplasia or fetal hydrops. Management may include prenatal surgery, shunting and, rarely, an EXIT procedure during birth. A few children may require extracorporeal membrane oxygenation postnatally.     

Ventilatory responses to hypercapnia and hypoxia in conscious cystic fibrosis knockout mice Cftr-/-

This study was designed to examine the ventilatory performance and the lung histopathology of cystic fibrosis knockout mice (Cftr-/-) compared with heterozygous (Cftr+/-) or wild-type (Cftr+/+) littermates. Ventilation was recorded in conscious animals using whole-body plethysmography. Tidal volume (VT), respiratory frequency (f), and minute ventilation (VE) were measured during air breathing and in response to various levels of hypercapnia (2, 4, 6, or 8% CO2) or hypoxia (14, 12, 10, or 8% O2). The results for Cftr+/- and Cftr+/+ were pooled into one control group because they did not differ. In air and in response to hypercapnia, VE, VT, and f were similar in Cftr-/- mice and in controls. During graded hypoxia, VE was decreased in Cftr-/- mice at 10 and 8% O2 because of a lower f. Histology showed neither inflammation nor obstruction of airways in Cftr-/- mice. Morphometric analysis showed alveolar dilation as a result of either distension or impaired development. In conclusion, cystic fibrosis knockout mice have normal baseline breathing and ventilatory response to hypercapnia but a decreased ventilatory response to severe hypoxia. This latter result associated with the morphometric analysis suggests that Cftr-/- mice may exhibit immaturity of the respiratory system.     

The hemodynamic effects of intrauterine hypoxia: an experimental model in newborn lambs.

An experimental animal model of intrauterine hypoxia and respiratory distress in newborn lambs was produced by inducing maternal hypotension. Serial hemodynamic data indicated that the oxygenation defect in the lambs was due to right-to-left shunting of blood through fetal channels rather than within the lungs. Shunting was mainly across the foramen ovale, but, in severely distressed animals, significant right-to-left shunt also occurred through the ductus arteriosus. Left-to-right shunts across the ductus arteriosus were found in lambs with milder respiratory distress. The implications of perinatal hypoxia as it affects the pulmonary vascular bed in human neonates with the respiratory distress syndrome (hyaline membrane disease) and persistence of the fetal circulation are discussed. It is speculated that the early pulmonary vascular esponses in the two diseases may be identical.     

Pulmonary vasodilator strategies in neonates with acute hypoxemic respiratory failure and pulmonary hypertension

The management of acute hypoxemic respiratory failure (AHRF) in newborns continues to be a clinical challenge with elevated risk for significant morbidities and mortality, especially when accompanied with persistent pulmonary hypertension of the newborn (PPHN). PPHN is a syndrome characterized by marked hypoxemia secondary to extrapulmonary right-to-left shunting across the ductus arteriosus and/or foramen ovale with high pulmonary artery pressure and increased pulmonary vascular resistance (PVR). After optimizing respiratory support, cardiac performance and systemic hemodynamics, targeting persistent elevations in PVR with inhaled nitric oxide (iNO) therapy has improved outcomes of neonates with PPHN physiology. Despite aggressive cardiopulmonary management, a significant proportion of patients have an inadequate response to iNO therapy, prompting consideration for additional pulmonary vasodilator therapy. This article reviews the pathophysiology and management of PPHN in term newborns with AHRF while highlighting both animal and human data to inform a physiologic approach to the use of PH-targeted therapies.     

Persistent fetal circulation

Persistent fetal circulation (PFC), also known as persistent pulmonary hypertension of the newborn, is defined as postnatal persistence of right-to-left ductal or atrial shunting, or both in the presence of elevated right ventricular pressure. It is a relatively rare condition that is usually seen in newborns with respiratory distress syndrome, overwhelming sepsis, meconium and other aspiration syndromes, intrauterine hypoxia and ischemia, and/or neonatal hypoxia and ischemia. This condition causes severe hypoxemia, and, as a result, has significant morbidity and mortality. Improved antenatal and neonatal care; the use of surfactant; continuous monitoring of oxygenation, blood pressure and other vital functions; and early recognition and intervention have made this condition even more rare. In modern neonatal intensive care units, anticipation and early treatment of PFC and its complications in sick newborns are commonplace. Thus, severe forms of PFC are only seen on isolated occasions. Consequently, it is even more imperative to revisit PFC compared with the time when there were occasional cases of PFC seen in neonatal intensive care units, and to discuss evolving treatment and management issues that pertain to this syndrome.     

Recurrent cyanotic episodes with severe arterial hypoxaemia and intrapulmonary shunting: a mechanism for sudden death.

The pathophysiology of recurrent cyanotic episodes has been investigated in 51 infants and children. Episodes began at a median age of 7 weeks (range 1 day to 22 months, 39 at less than 4 months). They were characterised by the rapidity of onset and progression of severe hypoxaemia with early loss of consciousness from cerebral hypoxia. The most common precipitating factor was a sudden naturally occurring stimulus from pain, fear, or anger. In uncontrolled trials, cyanotic episodes were reduced in frequency and severity by tetrabenazine (n = 15) and additional inspired oxygen (n = 10). Eight patients died suddenly and unexpectedly (four during cyanotic episodes). Twenty eight patients underwent physiological studies during cyanotic episodes. There was no evidence of seizure activity at the onset and although prolonged absence of inspiratory effort with continued expiratory efforts was common, breathing sometimes continued. Episodes were not caused by upper airway obstruction and sometimes occurred during positive airway pressure ventilation. The rapidity of fall in arterial oxygen pressure and continued breathing suggested a right to left shunt of sudden onset. The results of contrast echocardiography and lung imaging studies confirmed that this was occurring within the lungs. These cyanotic episodes included both intrapulmonary shunting and prolonged expiratory apnoea. They are best explained by interactions between central sympathetic activity, brainstem control of respiration and vasomotor activity, reflexes arising from around and within the respiratory tract, and the matching of ventilation to perfusion in the lungs. They are a cause of sudden unexpected death in infancy and early childhood.