Whether an infant requiring ECMO should be sent directly to an ECMO center or immediately placed on HFV and nitric oxide has created discord in the NICU.

It is one of the most difficult decisions encountered in the neonatal intensive care unit (NICU), and like so many decisions made there, it needs to be made quickly: when a newborn might later require extracorporeal membrane oxygenation (ECMO), should that infant be transported to an ECMO center immediately, or should the tertiary care facility first try to manage the neonate using high-frequency ventilation (HFV) and nitric oxide?

According to many NICU practitioners, the decision is difficult to make because when HFV with nitric oxide fails, there may be very little time left for the infant to reach an ECMO center. With rare exceptions, air and ambulance transport during nitric-oxide therapy is not yet available. This means that nitric oxide must be discontinued during transport; the full size HFV unit does not travel either. Transferring the infant to another form of mechanical ventilation might increase the risk of volutrauma or barotrauma.

Bill Howard, MBA, RRT, director of respiratory care at New England Medical Center and Floating Hospital for Children, Boston, says, “A lot depends on where the facility is located. Here in the city, where we have two ECMO centers only a few minutes away, we can try nitric oxide and HFV with very little risk. At an outlying facility that may be 2 or more hours distant, they have a much bigger problem.”

According to Howard, it is not a good idea to withdraw nitric oxide abruptly. “Even at a high dose, we don’t wean more than 20% of the total at a time,” he says. If the nitric oxide concentration is decreased too rapidly, pulmonary hypertension can rebound, with a sharp increase in the difficulty of oxygenating the blood. Practitioners need to weigh the fact that nitric oxide has been used only under investigational drug protocols. The HFV unit also needs to be used frequently if practitioners are to maintain their highest level of skill in its application.

Would the best policy for an outlying facility be to transport the infant to a center that has ECMO available, even before starting nitric oxide or HFV? Not in all cases, Howard says. Most facilities are very reluctant to separate parents from their newborn by sending the infant to a distant ECMO center; separation can increase the stress levels of some parents to intolerable levels. If possible, the infant should be treated near the parents’ home. Recently, practitioners have also found that when treatment with nitric oxide and HFV is warranted, patients do better if therapy is started immediately.

Eligibility criteria for extracorporeal membrane oxygenation (ECMO)
1. Weight 2000 g and/or gestational age 34 weeks
2. No more than 7 to 10 days on assisted ventilation
3. Reversible lung disease
4. No major intracranial hemorrhage or severe uncorrected coagulopathy
5. Primary disease process is not a congenital heart defect
(this is changing as more defects can be repaired)
6. Failure of maximal medical management

Indications for ECMO
1. Hypoxia for longer than than 4 hours
2. Oxygen index of less than 40
3. P-AO2 gradient of less than 400 mm Hg
4. PaO2 of less than 50 on mechanical ventilation with peak inspiratory pressure of more than 35 or mean airway pressure of more than 20
5. pH below 7.2 despite therapy, with rising lactic acid levels

Disease states in which ECMO may be used
1. Meconium aspiration
2. Congenital diaphragmatic hernia
3. Barotrauma
4. Respiratory distress syndrome

Table 1. ECMO criteria.

Donna Kelly, RRT, associate director of respiratory care at New England Medical Center, says,“When people started debating this issue and stating that facilities shouldn’t use nitric oxide unless they had ECMO nearby, I don’t think that anyone predicted that we would see a 60% decrease in transfers to ECMO.” According to Kelly, some of the situations traditionally treated using ECMO, including meconium aspiration, sepsis, and barotrauma, can almost always be managed using HFV and nitric oxide. “First, I don’t think that they realized how beneficial nitric oxide was going to be. Second, I don’t think that they anticipated how quickly people would move forward to get this benefit for their patients,” she says.

As Kelly points out, while waiting for nitric oxide to be approved by the US Food and Drug Administration (FDA), numerous facilities have treated patients under investigational protocols. In the process, practitioners have learned much about how to employ the gas effectively. They are also gaining a sense of how wide its applications may eventually be. “For example, I would not have predicted that it would be useful after liver transplantation,” Kelly says. After a liver is transplanted, a child often experiences a period of reversible pulmonary hypertension. This condition is also common after heart transplantation and after the repair of congenital cardiac defects, as well as following other cardiac surgeries. According to Kelly, both pediatric and adult patients may experience pulmonary hypertension after intraoperative bypass devices are withdrawn. “Some of our small cardiac patients can have pulmonary hypertension for a period of 12 hours or so, just as a consequence of being on the bypass pump. We’ve seen what the results of that can be: a baby can just spiral downhill,” Kelly says. Nitric oxide, which is a selective pulmonary vasodilator, can often relieve the condition. “If we can do something to improve survival for any of these procedures, it would be wonderful,” Kelly adds.

Among those children who would otherwise need ECMO, a course of HFV and nitric oxide may improve overall outcomes as well. “We don’t know what the long-term consequences of nitric oxide therapy may be, but we know what the implications of ECMO are,” Kelly says, noting that ECMO, which requires heparinization, carries a risk of cerebral hemorrhage. For this reason, an ECMO center will often use HFV and nitric oxide first to see whether ECMO can be avoided. “Now, when we make an ECMO call, the center asks us whether we have had the baby on HFV and whether we have tried various strategies. The staff wants to know whether we are using nitric oxide and what differences are seen in the baby’s Po2 at different concentrations,” Kelly says. In some cases, however, there is no doubt that the child will need ECMO. “As a bridge to ECMO for kids who are really unstable, nitric oxide could help maintain an adequate Po2 until the infant reaches the ECMO site,” Kelly says.

For outlying facilities, being able to use nitric oxide during transport could resolve the issue of when to start therapy, Kelly believes. “Here in Boston, we have conducted training sessions for an organization that does medical air transport. It has been trying to determine what sort of guidelines might be set up by the American Association for Respiratory Care, and its staff has come to our facility to observe when we have a patient on nitric oxide,” Kelly says.

According to Deborah Igo, RRT, perinatal pediatric specialist at Maine Medical Center, Portland, being able to transport an infant using nitric oxide to an ECMO center might make it more feasible to attempt treating more neonates locally. Otherwise, she says, there are no options when maximal HFV and nitric-oxide levels have already been tried. “How do we get the baby to an ECMO center at that point?” Igo says. Even in those rare instances when her facility sends neonates to Boston for ECMO, the infants typically use HFV with nitric oxide first. “Almost all facilities avoid ECMO,” Igo says. “Right now, we don’t offer nitric oxide, but if we had that capability here, it would be much less stressful for the family.” Along with the physicians and the other RCPs in her unit, Igo has taken part in many discussions of how this capability could be offered safely. “We’d need to leave some room on the HFV unit,” she says; if maximal levels are approached, “at that point, we would look at transferring the baby.” Igo thinks that 2 to 3 years will elapse before an infant can be transported using HFV.

Setting up communication with the ECMO center is vital, according to Mark Rogers, RRT, research therapist at Loma Linda University Medical Center and Children’s Hospital, Loma Linda, Calif. “As the technology becomes easier to obtain, and outlying facilities are able to try managing sicker and sicker babies, I think that their physicians should touch base with the physicians at the ECMO facility,” Rogers says. If the case is one in which experience has shown a high likelihood that ECMO will eventually be needed, perhaps the infant should be transported prior to the initiation of either HFV or nitric-oxide therapy. “Once you start therapy such as that, it is more and more difficult to transport the baby to an ECMO center,” Rogers says; neonates who are failing are the ones who will need transport, and those infants can probably be shifted to conventional ventilation, but it is difficult to discontinue nitric-oxide use for the transport period.

New measures such as amnioinfusion and saline infusion to thin secretion have improved the management of meconium aspiration, but there will still be times when an infant starts to fail under local management and must reach an ECMO center as soon as possible. In such cases, advance communication between the two facilities becomes important. According to Rogers, it takes about an hour to set up the ECMO unit; this can be done while the infant is being transported. On arrival, surgeons who have been alerted in advance can complete the child’s cannulation within 30 minutes.

Judging by the eagerness that facilities have shown to obtain permission to use nitric oxide investigationally, Rogers expects FDA approval to bring a host of problems to ECMO centers. “I anticipate seeing patients who were started on nitric oxide at outlying centers because the staff was sure that these patients could be managed there,” Rogers says. He expects to see sicker patients because he finds air transport using nitric oxide is likely to become available, although more must be learned about the effects of altitude on the gas and the patient’s physiological response to it. This ability will encourage broader use of HFV with nitric oxide. He says, “These patients will have had perhaps an extra 4 or 5 days on nitric oxide, the disease process not having gotten better (and, perhaps, having gotten worse). We are going to be transporting a very sick patient.”

Sandra Wadlinger, RRT, neonatal specialist for respiratory care at Children’s Hospital of Philadelphia, agrees with Rogers. “I wonder if we might not get kids here a little more quickly if the people at the outlying hospital did not try everything first,” she says, while admitting that hers is not an objective point of view because the patients whom she sees have already been treated unsuccessfully elsewhere. On the other hand, she has no doubt that ECMO use has decreased. Antenatal steroids and lower infection rates have contributed to the improved statistics, but, she adds, “I don’t think that there is any doubt that we have decreased our ECMO numbers, even among the babies whom we treat here, through the use of HFV and nitric oxide,” she says.

Tina Carmichael, RRT, agrees. As an ECMO specialist at Children’s Hospital Medical Center, Boston, Carmichael also sees the issue from the point of view of the ECMO center. “It seems to me that we are able to manage babies better when we get them at an earlier point,” she says. Because of the advent of newer therapies, her program is rarely called on to perform ECMO for newborns unless they have diaphragmatic hernias. “We just don’t do a lot of pulmonary ECMO any more—except in a really hard case of sepsis. We have had just one such case in the past 2 years,” Carmichael says. Cardiac ECMO now prevails, “but the conditions for which we traditionally used ECMO (primary pulmonary hypertension of the newborn and meconium aspiration) can usually be managed without it,” Carmichael says. HFV and nitric oxide have made this possible.

Will these modalities also make it possible for outlying centers to treat more of their patients locally and avoid transporting them to ECMO centers? According to Igo, outlying facilities typically serve large geographic areas. Maine Medical Center receives patients from distant parts of New Hampshire and Maine. “For these parents, coming into Portland is traumatic enough. Sending their babies into Boston is like sending them to Shanghai,” Igo says. Being able to treat neonates using nitric oxide could be beneficial to such families, and Igo believes that being able to start therapy using nitric oxide immediately could be helpful to the infant as well. This capability will become available only when it is possible to transport the infant with nitric oxide in use, in the event that local management starts to fail.

India Smith is a contributing writer for RT.