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Historical Perspectives

2003; American Academy of Pediatrics; Volume: 4; Issue: 12 Linguagem: Inglês

10.1542/neo.4.12.e335

1526-9906

Alistair G.S. Philip,

Neuroscience of respiration and sleep

It is difficult to know with certainty who first applied assisted ventilation for the management of neonates who have respiratory distress syndrome (RDS), which was known more commonly as hyaline membrane disease (HMD) at the time of initial assisted ventilation use. However, Maria Delivoria-Papadopoulos and Paul Swyer definitely were among the first to use endotracheal tubes and positive pressure ventilation, and their successful use of this methodology is the choice for this month's Historical Perspective. In fact, as Dr. Delivoria-Papadopoulos indicates in her accompanying commentary, assisted ventilation may have been employed successfully on occasion a decade earlier. Undeniably it was used in some countries for infants who had neonatal tetanus, but these neonates had normal lungs, and early reports concerned the use of tracheostomy tubes. (1) Several groups embarked on the course of assisting ventilation in RDS (HMD) in the early 1960s. Some used positive pressure ventilation, including Strang and Reynolds in London, (2) Thomas and coworkers at Stanford, (3) and Heese and colleagues in Cape Town. (4) Others employed negative pressure ventilators, such as Stahlman and associates in Nashville (5) and Stern and colleagues in Montreal. (6) Indeed, negative pressure ventilation could have been used earlier. In 1889, Alexander Graham Bell "designed and built a body type respirator for use with newborn infants. Presented to the American Association for the Advancement of Science in Montreal, the invention met with little enthusiasm." (7) The design and device are preserved in a museum in Nova Scotia, Canada.In 1969, a conference on assisted ventilation was organized in Paris by Professor Alex Minkowski, with representatives from France, Belgium, England, South Africa (data from Sweden), Finland, Canada, and the United States. (8) The big question was whether neonatologists should continue to provide assisted ventilation (perhaps more aggressively) or whether the possible complications outweighed the potential advantages. Bronchopulmonary dysplasia (or "respirator lung") had been described, (9)(10) and this complication proved to be a serious disadvantage for many years. Needless to say, assisted ventilation did not stop at that time.Soon to follow was the realization that continuous distending pressure (particularly continuous positive airway pressure) was very beneficial in minimizing or preventing atelectasis in RDS. (11) This will be the featured topic in next month's Historical Perspective.The magnitude of the disastrous 1952 poliomyelitis epidemic in Europe had a major impact in the medical world. During the years of the epidemic, respiratory muscle weakness and bulbar respiratory failure often were treated successfully with tank-type negative pressure ventilators of the Drinker design or by continuous positive pressure delivered manually through an endotracheal tube or tracheostomy. Many affected children were weaned to a negative pressure chest cuirass or to a foot-tilt rocking bed as they improved. As a result of these revolutionary new treatments, mortality in spinobulbar poliomyelitis was reduced from 80% at the beginning of the epidemic to 25% with tracheostomy and manually controlled respiration.In Greece, during the catastrophic 1958 poliomyelitis epidemic, the morbidity and mortality among children, including infants from 2 months of age, was so overwhelming that at the request of the Hellenic Red Cross, the World Red Cross sent to Athens a team of experts from Sweden consisting of physicians, nurses, and physiotherapists with the necessary equipment. I was recruited to work in the special polio unit established in Athens for the treatment of respiratory failure, and for the first time I faced the devastating effects of respiratory failure.With initially elementary equipment (bag and oxygen mask), we could not sustain respiration in children who had polio; they were dying helplessly without the assistance of a mechanical ventilator. With the Swedish team, we began to use the Drager iron lung, the Freiberger, the Lundia Kifa positive pressure, and the "rocking bed" to assist children who had potentially fatal respiratory failure. (1) A number of children survived, but the 19 young infants who could not be saved stand out in my memory.Concurrently, a number of positive pressure ventilators, usually volume-controlled, were designed and put into use in major medical centers throughout Europe, making the tank (iron lung) largely obsolete. By 1959, two such ventilators had been used on newborns—a volume-controlled ventilator (the Engstrom respirator) in Sweden and the East Radcliff pump, also a volume-controlled ventilator, in South Africa.Upon starting my residency in the United States, I faced for the first time the high mortality of infants who had HMD and died from respiratory failure. The images of the young children from Greece who had bulbar polio came back vividly, and I began to want to attempt ventilating these babies who otherwise would have died.In July 1962, at the Hospital for Sick Children in Toronto, I was allowed to intubate preterm babies who had HMD only after they were pronounced dead by the housestaff. For 6 long continuous months, our failure to sustain life in those intubated and ventilated babies was met with sadness and despair. However, perseverance, persuasion, and the agony of attempting to resuscitate babies who had died combined with the use of the Bird Mark VIII Respirator led to my first survivor, an 1,800-g infant of 34 weeks' gestation who had had complete cardiorespiratory arrest on January 9, 1963. The infant was discharged home on the 47th postnatal day with minimal perihilar infiltration radiologically, no abnormal symptoms or physical signs, and a weight of 2,800 g. Examination of the patient at 6 months of age disclosed no neurologic or other abnormality, and the chest radiograph was normal. I reported our results to the Society for Pediatric Research in May 1963 and published the paper with Paul Swyer entitled "Assisted Ventilation in Terminal Hyaline Membrane Disease." (2)The first report describing the use of assisted ventilation in the treatment of atelectasis neonatorum was by Donald and Lord in 1953. (3) Subsequently, reports accumulated in the literature of the use of assisted ventilation in the treatment of newborn RDS. (4)(5)(6)(7)(8)In those early days, we felt the risks of ventilation were so great that infants should not be mechanically assisted unless they could not otherwise survive. Consequently, the criteria used to select infants for ventilation were very rigorous: inability to restore respiration using bag and mask, sustained bradycardia of less than 60 beats/min for 1 minute or cardiac arrest of 3 minutes, pH of less than 7.0, Po2 of less than 30 to 40 mm Hg in 100% oxygen, and Paco2 of greater than 80 mm Hg. The hesitancy to use mechanical ventilation, especially in small preterm infants, was based on the significant hazards associated with this mode of therapy. Of particular concern were the small size of the endotracheal tube and its connections, the susceptibility of the preterm infant to infection, and the high pressures that often were required to achieve adequate gas exchange. In spite of the reluctance to ventilate babies, early reports did demonstrate a small but definite reduction in mortality among infants who weighed more than 1,800 g and who did not require ventilation before 24 hours after birth. (9)From the milestones of the early 1960s, when mechanical ventilatory support was introduced in the management of newborn respiratory distress, until the end of the decade, little additional progress was made in reducing further the mortality of the critically ill infant, despite the introduction of various types of more sophisticated ventilators and various modes of using them for therapy. During this time, however, progress was made in understanding the nature of newborn RDS and the complexity of the pathophysiology of the immature lung. (10)The 1971 introduction by Gregory and associates of continuous distending pressure (continuous positive airway pressure [CPAP]) using an endotracheal tube was a breakthrough in the treatment of newborn RDS. (11) They demonstrated dramatic improvement of oxygenation, presumably by recruiting narrowed terminal conducting airways and incompletely collapsed air spaces. The resultant increased lung volume following a given end-distending pressure improved gas exchange and reduced regional vascular resistance and right-to-left shunt in most infants. Subsequently, Rhodes and Hall (12) applied CPAP by face mask and showed a significant decrease in mortality among infants weighing more than 1,500 g who had RDS, and in 1973, Kattwinkel and associates (13) extended the use of CPAP in applying end-distending pressure using nasal catheters positioned in the midnares. These techniques left the trachea undisturbed and preserved the infant's grunt, but erosion of the nasal septum and gastric distension sometimes occurred. Subsequent studies (14)(15) following the original report by Gregory also documented significant reductions in oxygen requirements and oxygen exposure with the use of CPAP. Most studies indicated that early intervention with CPAP increased survival, presumably by stabilizing small air spaces, thereby preventing disruption of surfactant films and ameliorating the disease process. CPAP was found to be beneficial in the management of RDS when the patient required less than 60% oxygen to maintain a Pao2 of 50 to 60 mm Hg. Optimal levels of CPAP may be titrated according to the level of inspired oxygen. Generally, a level of 5 to 6 cm H2O is used initially and may be increased as the need for oxygen approaches 100%.Although CPAP is one treatment currently used to treat RDS, it is not without adverse affects. Pathophysiologic consequences of CPAP, such as increased work of breathing, decreased lung compliance, and decreased tidal volume, may result from overdistention of the relatively normal air spaces. During recovery from RDS, there also may be increased transmission of pressure to the air spaces and an increased incidence of interstitial emphysema and pneumothorax. Additionally, cardiac output may be impaired due to compression of thoracic veins and pulmonary capillaries.Both intermittent positive pressure ventilation and intermittent negative pressure ventilation have been effective in correcting blood gas derangements of RDS and decreasing mortality. The use of intermittent negative pressure ventilation is limited in infants weighing less than 1,500 g and in those who have hypercapnia. (16)(17)(18)(19) Therefore, intermittent positive pressure ventilation has been used more extensively to treat RDS in infants of all birth weights.Intermittent positive pressure ventilation initially was used with high flow rates during inspiration, a low inspiration-expiration ratio (I:E), and high frequencies, which were consistent with the infant's respiratory pattern. As a result, peak inflation pressures tended to be high. The emphasis on patient-triggered assisted ventilation did not improve oxygenation significantly. (20) The effects of independent variation of rate, I:E ratio, and peak inflation pressure indicated that ventilation improved with higher frequencies or higher peak inflation pressures, while oxygenation improved with lower frequencies or higher peak inflation pressures. (21)(22)(23)Intermittent positive pressure ventilation also has been used with continuous distending pressure or, as it was formerly called, positive end-expiratory pressure. Because mean airway pressure has been shown to correlate with oxygenation, the use of positive end-expiratory pressure can decrease both peak inflation pressures and the fraction of inspired oxygen. (24) By maintaining constant mean airway pressure, either a square- or sine-wave pressure profile in the respiratory cycle may be used. By using the pressure plateau of square-wave ventilation, gas may enter areas of high resistance and provide better expansion of the open low-V/Q (ventilation-perfusion ratio) compartment. (25) Conversely, a sine wave produces less overdistention of more normal air spaces.During the pioneering days of mechanical ventilation, associated chronic complications and sequelae did not become apparent because gravely ill infants succumbed. However, as the number of surviving infants increased due to ventilatory assistance, improved technology, and organized regional medical centers, so did the number of sequelae of ventilator treatments. In 1967, Northway and associates described the syndrome of bronchopulmonary dysplasia among infants surviving severe RDS who had required mechanical ventilation. (26) The incidence of bronchopulmonary dysplasia varied from 5% to 30%; the mortality rate was 38%. Its cause still is disputed, but factors such as elevated inspired-oxygen concentration, positive-pressure ventilation, endotracheal intubation, and duration of primary therapy have been implicated. (27)(28) Oxygen alone has been shown to produce vascular engorgement, edema, hemorrhage, and epithelial necrosis, although the incidence of bronchopulmonary dysplasia is lower in infants who do not receive endotracheal intubation and positive pressure.Although the mortality rate for infants suffering from RDS has decreased with increasingly sophisticated use of mechanical ventilation, questions regarding the quality of life of the survivors have been raised. Initial follow-up studies revealed significant neurologic sequelae. Subsequent follow-up studies indicated, however, that the prognosis for even the most critically ill newborn is good if intervention is early enough to prevent profound hypoxia and acidosis, temperature is maintained, and nutrition is provided. Most of the morbidity centers around the very low-birthweight infant (<1,000 g). If optimal care is instituted during the perinatal period, the consensus is that a favorable prognosis on the quality of life of even these survivors can be anticipated.In the last 40 years, we have seen exponential progress in the care of high-risk newborns from almost 100% mortality of a 1,500-g preterm infant who has cardiorespiratory, metabolic, and nutritional problems to an optimal survival rate close to 100%. The next frontier needs to be the elimination of neurologic sequelae. We need to continue investigating and elucidating the basic cellular mechanisms that will further enable us to maintain the optimal quality of life for our precious preterm babies.