Vol. 12 •Issue 5 • Page 54
A New Era in Treating Congenital Diaphragmatic Hernia
Too Much Ventilation Can be Lethal for These Children
Treating patients with congenital diaphragmatic hernia allows a unique opportunity to care for infants whose lungs may be barely large enough to keep them alive.
CDH is a serious birth defect involving a hole in the muscle that separates the abdomen from the chest. But because of associated pulmonary hypoplasia, this hole brings about a complex interplay of pathophysiology involving the lungs, heart and vascular beds.
The survival rate of children with CDH was only 63 percent in 1998 at centers with a strong interest in treating the condition, the Congenital Hernia Study Group reported.1 While some children over the years likely have succumbed in situations where they didn’t receive enough necessary treatment, many other children likely have died from receiving too much therapy.
CDH occurs approximately once out of every 3,000 live births, and roughly 1,300 children were born with CDH in the United States in 2000.2 There’s no known relation of ethnicity to CDH, and slightly more boys than girls are born with the disease, although not all reports agree with that assessment.2 CDH is one of the common causes of unexpected respiratory distress in the delivery room, but it’s being diagnosed with increasing frequency by prenatal ultrasound.
SPECTRUM OF CDH
CDH’s severity varies dramatically. Newborns with mild CDH may not develop respiratory distress until hours, days or even years later, though the vast majority of cases have trouble in the minutes after birth. This variation in clinical presentation is related to the degree of pulmonary hypoplasia, which is the major underlying deficit in these babies and is caused by the mass of abdominal contents herniated into the chest during prenatal development. Both lungs are usually affected, although ipsilateral hypoplasia is much worse.
While there’s no universally accepted anatomical grading scale of CDH, the position of a newborn’s organs can give a clinician an idea of the condition’s severity. Babies with the more common left-side presentation of CDH (left-sided defects outnumber right-sided about four to one) who have a herniated intestine but a stomach and liver in a normal position represent milder disease. Babies with the intestine and stomach protruding into the chest are worse, and newborns with intestine, stomach, and liver protruding into their chest represent the more severe end of the spectrum.
Children with right-sided CDH also have a spectrum of severity, but it’s harder to define anatomically. Virtually all will have herniation of the liver into the chest, but with variable amounts that are harder to quantify. CDH infants’ chances of survival also may be affected by associated anomalies, such as severe congenital heart lesions, chromosomal anomalies or syndromes associated with multiple defects.
TAKING CARE OF LUNGS
CDH lungs aren’t only smaller, they’re also structurally abnormal with fewer bronchial divisions compared to normal and an overall reduction in alveoli.3 Those alveoli that are present are less mature, and fewer abut the terminal capillaries, leading to impaired gas exchange.
In short, these lungs don’t move air as well as normal lungs, and to further complicate matters, they don’t move blood as well either. The pulmonary vascular bed in CDH lungs is both smaller and more muscular than normal.4 This puts the child at a higher risk of vasoreactive pulmonary hypertension, a common and severe problem.
Because of these many difficulties, it’s incumbent upon the clinician to be cautious when handling these small, fragile lungs. The most common and potentially fatal mistake is to ventilate these children too aggressively. Resuscitation in the delivery room is no exception to this need for prudence.
When the diagnosis is known or suspected, endotracheal intubation is preferred over bag-mask ventilation so as to avoid blowing air into the stomach and intestines, which will then further compress the lungs. Initially following intubation, CDH newborns may have poor chest movement, but every attempt should be made to keep peak inspiratory ventilation pressures to 25 cm of water or less.
Vigorous attempts to inflate the lungs, or to make the chest move too much too soon, will result in lung injury, which may present dramatically as pneumothorax. This injury, although very recoverable in a patient with otherwise normal lungs, may be unrecoverable in a baby with significant lung hypoplasia.
Researchers have shown in an elegant series of experiments that pneumothorax is a late finding in ventilation-induced lung injury and that significant underlying lung damage occurs before, or in addition to, pneumothorax.5-7
Following delivery, CDH babies may improve rapidly, slowly or not at all. It takes significant judgment and experience to know when — and how much — to escalate therapy.
Echocardiography likely will show significant pulmonary hypertension, which is due to incompletely inflated lungs and to increased pulmonary vascular reactivity. This often results in significant shunting of blood right to left across the ductus arteriosus, and so monitoring of both pre- and post-ductal oxygen saturations is essential. Management decisions generally should be based on pre-ductal oxygen saturations, for even with significant shunting, oxygen delivery to the body is usually adequate if pre-ductal saturations are good.
FAILED TREATMENT STRATEGIES
Unfortunately, previous aggressive attempts to reduce, eliminate and prevent shunting resulted in the development of a therapeutic strategy now recognized as harmful. Published data from the early 1980s noted that hyperventilation and respiratory alkalosis acutely reduced pulmonary vascular resistance, decreased or eliminated right to left shunting, and improved oxygenation in infants suffering from persistent pulmonary hypertension.8
This valid observation, however, can be toxic for CDH patients because hyperventilation asks lungs that are small, fragile and immature to excrete higher than normal amounts of CO2. As a result, two failures can happen. First, patients usually exhibit tachyphylaxis to the effects of hypocarbia and require escalating levels of ventilation to maintain the pulmonary vasodilating effect of this therapy. Patients may die abruptly when the effect ultimately wears off. Second, hyperventilation is hard on the fragile lungs. Even a small amount of ventilation-induced lung injury can convert a potentially survivable child with CDH into a nonsurvivor.
Based primarily on pioneering work that focused on avoiding hyperventilation in CDH infants, the University of Florida abandoned hyperventilation in CDH management in 1992.9-11 Prior to that change, 14 consecutive CDH patients at the university had been treated with “gentle” hyperventilation (average peak inspiratory pressure 28 cm H2O) with extracorporeal membrane oxygenation as a backup when hyperventilation failed. Just seven of those 14 (50 percent) survived to discharge.
Following our therapy change, we treated 53 patients with CDH, who didn’t have associated lethal anomalies, through 1998. We strictly avoided hyperventilation and alkalosis, using standard, neonatal, time-cycled, pressure-limited synchronized intermittent mandatory ventilation.
Compared to the previous 14 patients who were hyperventilated, mean PIP at 24 hours of life dropped from 28.5 cm H2O to 22 cm H2O, pneumothorax rate dropped from 43 percent to 2 percent, and PCO2 rose from 35 mm Hg to 44 mm Hg. Most importantly, survival to discharge rose to 89 percent (47/53) when hyperventilation was abandoned and PIP was strictly limited. Of 25 consecutive CDH patients who were both born and treated at the University of Florida, 23 survived (92 percent) to go home with their families.11
OTHER TREATMENT OPTIONS
While the University of Florida and a few others have reported excellent survival statistics by supporting CDH patients primarily with conventional ventilators, others have reported improved results using high-frequency oscillatory ventilation.12-15 Regardless of the ventilator used, however, strictly limiting lung inflation pressures to avoid alveolar overdistension is crucial. This often means accepting higher PCO2 and lower PO2 than desired.
It’s attractive to postulate that exogenous surfactant and/or inhaled nitric oxide would be helpful in treating these children, but no clear evidence of improved survival has been published. We use exogenous surfactant for CDH babies less than 35 weeks gestation. Inhaled nitric oxide has been of more value, but it has had no significant effect on the eventual need for ECMO, nor did its use in our population increase survival.11,16 A significant advantage of inhaled nitric oxide, though, is its short onset of action compared to the time it takes to get a patient onto ECMO.
ECMO, a form of lung and heart support similar to continuous heart-lung bypass, is used to support between 25 percent and 50 percent of children with CDH whose lungs fail in the first few days of life. ECMO improves CDH survival by allowing lung rest, lung maturation and resolution of pulmonary hypertension; therefore, ECMO is an important part of the therapeutic armamentarium for patients who fail other therapies.12
CONCLUSION
CDH remains a serious birth defect with a significant risk of mortality. While relatively new tools such as nitric oxide and fancy ventilators may have roles in CDH management, it’s crucial to understand that too much ventilation can be lethal for these children. The day of therapeutic hyperventilation in these children has passed. Newer concepts applied by a dedicated and experienced medical team can result in survival rates of 80 percent to 90 percent in otherwise uncomplicated cases. These survival rates were unheard of until recently, and not all physicians are aware of how much progress has been made and how much hope currently exists for these children.
Dr. Kays is a pediatric surgeon with a strong interest in ventilation and critical care at the University of Florida in Gainesville. He leads the university’s congenital diaphragmatic hernia efforts and has directed the extracorporeal membrane oxygenation program since joining the faculty in 1992. He can be reached at [email protected] or [email protected].
For a list of references, please call John Crawford at (610) 278-1400, ext. 1499, or visit www.Respiratory-care-sleep-medicine.advanceweb.com.
Table 1. Congenital Diaphragmatic Hernia Treatment Strategy at the University of Florida
• Light sedation by benzodiazepine infusion. No paralysis.
• Conventional SIMV pressure-limited ventilation.
• Ventilator rate set to patient comfort and clinical state.
• .PIP to lowest level which provides adequate chest movement
(usually 20 cm H2O to 24 cm H2O).
• Mean airway pressure < 11 cm H2O.
• PIP > 25 cm H2O used as bridge to ECMO.
• Hyperventilation and alkalosis are strictly avoided.
• High frequency oscillatory ventilation, at low mean airway pressures, is used in selected cases not responding to conventional ventilation.
Table 2. Ventilation Goals for Congenital Diaphragmatic Hernia at the University of Florida
• Goal PaCO2: 40 mm Hg to 60 mm Hg, but will tolerate higher to avoid lung injury
• Goal PaO2: 80 mm Hg to 100 mm Hg, but will tolerate lower to avoid lung injury
• Goal pH: 7.20 or greater, and will treat with NaHCO2 if necessary
Children with CDH Have Reason to Hope
Cathie and Carl heard it in Cleveland. Anne and Mike heard it in Phoenix. The message for each couple was the same: “Your unborn child has a serious defect called congenital diaphragmatic hernia. Your child’s deformity is severe, and survival is 50-50 at best, probably less. We are very sorry. We can offer you termination of the pregnancy, if you are ready.”
The news was absolutely devastating, but each couple’s response was the same. “Termination was never an option for us,” reflect Carl and Cathie. “We knew there must be someone, someplace, that was doing better with this disease.”
Through information and support garnered through the Internet, each couple found its own route to the University of Florida, Gainesville, where survival rates in CDH patients hover around 90 percent. Each family decided to make the university town its home during their child’s delivery and treatment at the university’s Shands Children’s Hospital.
Luke, son of Cathie and Carl, came first. Born at 38 weeks with a severe left-sided CDH, he had small bowel, colon, stomach and liver protruding into his left chest. His spleen had herniated behind the esophagus into the right chest, mimicking a bilateral diaphragmatic hernia. Both lungs were affected, and the lung hypoplasia was severe. Following birth and a period of poor lung function, he stabilized somewhat on synchronized intermittent mandatory ventilation with peak inspiratory pressures of 22 cm H2O.
At 16 hours of life, his already marginal lung function began to worsen. He underwent repair of his CDH at 18 hours of age and needed extracorporeal membrane oxygenation soon after the surgery. He stayed on ECMO support for an uneventful eight days and was extubated at 17 days of life. Following management of his lung and feeding issues, he was discharged home at 2 months of life on 200 cc of oxygen by nasal cannula. He’s now bright and thriving at 27 months old, and his prognosis is excellent.
Emma, her right chest nearly completely filled by liver, was born next. As a baby with a severe right-sided CDH, she had her share of ups and downs, but was ventilated successfully using SIMV and peak inspiratory pressures of 22 cm H20. She didn’t require ECMO.
Her CDH was repaired at 5 days of age, and she was extubated at 14 days. She worked through her own ventilation and feeding issues and was discharged home on 100 cc of oxygen by nasal cannula at 5 weeks of age. Emma is now 20 months old, thriving, and is normal by all accounts.
Carl and Cathie, Anne and Mike, now send their own message: The odds of survival with CDH, as well as outcomes, can be better than many doctors think. Theirs is a message of real hope.
—David W. Kays, MD
