PEDIATRICS Vol. 107 No. 2 February 2001, pp. 452

Pulmonary Hypertension-Hyperventilation Versus Alkali Infusion

To the Editor.

We read with interest the recently published study by Dr Walsh-Sukys et al on treatment variations and outcomes of newborns with persistent pulmonary hypertension of the newborn (PPHN).¹ Although within the text the authors call for a controlled study to compare hyperventilation to alkali infusion, the implication is left that perhaps the former treatment is preferable to the latter:

"Hyperventilation reduced the risk of extracorporeal membrane oxygenation (ECMO) without increasing the use of oxygen at 28 days of age. In contrast, the use of alkali infusion was associated with an increased use of ECMO and an increased use of oxygen at 28 days. Conclusion: Hyperventilation and alkali infusion are not equivalent in their outcomes in neonates with PPHN."

In view of recent data suggesting that gentle ventilation may avoid ventilator-induced lung injury,^2,3 we believe that the authors' implication could lead to potentially harmful therapeutic strategies in the management of PPHN. We suspect that the authors have not demonstrated a difference in outcomes between hyperventilation and alkali infusion in the management of PPHN, but have simply identified markers for the degree of illness in infants with PPHN.

For example, alkali infusion, pressors, and paralysis may be required for the sicker infants and also may be used to treat conditions other than PPHN (ie, metabolic acidosis, poor perfusion, and agitation or movement-associated worsening of oxygenation). Thus, use of these therapies is more likely a reflection of the degree of illness, rather than representing less favorable first-line treatments for PPHN. It follows, therefore, that those infants who are most ill would be more likely to require ECMO and/or supplemental oxygen at 28 days, regardless of the initial therapy they received. The authors concluded from Table 4 that hyperventilation appeared superior to alkali infusion in the management of PPHN because its use was associated with less mortality and a reduced need for ECMO. However, because mortality was even lower when neither therapy was used, one could also falsely conclude that using no therapy would be better than hyperventilation (perhaps a rational argument, but not shown by this nonrandomized, posthoc study design).

Although we agree that a controlled trial comparing the role of hyperventilation versus alkali infusion as initial therapy for PPHN would be ideal, it is unlikely that many centers would be willing to randomize patients to only one of these two strategies. As demonstrated in this study, 61% of the infants treated with either therapy were treated with both therapies and only 14% were treated with hyperventilation alone. We encourage the authors to reexamine their data to control for degree of illness (eg, oxygenation index) at the time various therapies were introduced. The implications of the conclusions coming from the highly respected NIH network may have untoward consequences in the treatment of PPHN.

Sheree Kuo
Victoria Camerini
Robert Boyle
M. Pamela Griffin
David Kaufman
John Kattwinkel
University of Virginia
Division of Neonatology
Charlottesville, VA 22908

REFERENCES

1. Walsh-Sukys MC, Persistent pulmonary hypertension of the newborn in the era before nitric oxide: practice variation and outcomes. Pediatrics. 2000; 105:14-20 [Abstract/Free Full Text]
2. Hudson LD Progress in understanding ventilator-induced lung injury. JAMA. 1999; 282:77-78 [Free Full Text]
3. Clark RH, Slutsky AS, Gerstmann DR Lung protective strategies of ventilation in the neonate: what are they? Pediatrics. 2000; 105:112-114 [Free Full Text]

In Reply.

We thank Dr Kattwinkel and colleagues for their comments on our observational study of the treatments used in persistent pulmonary hypertension of the newborn (PPHN). The writers are concerned that our article implies support for the use of hyperventilation in neonates with PPHN. The intent of our study was to generate hypotheses for exploration in future trials. Thus, we did not intend to endorse hyperventilation or any other treatment strategy in neonates with PPHN. In fact, we stated that "no individual therapy was associated with a reduced risk of death" (page 17 of our article). We refer Dr Kattwinkel and his colleagues to page 18, paragraph 1 for the requested analysis, where we note that patients treated without either hyperventilation or alkali were less sick than patients receiving either therapy alone, and those receiving one therapy were less ill than those receiving both treatments. Our data do not permit us to extend those interpretations. We further emphasize our conclusion that "optimal treatment of PPHN before the use of inhaled nitric oxide is unknown" in no way implies that hyperventilation is superior to induced metabolic alkalosis.

Michele Walsh-Sukys, and Avroy Faranoff
Case Western Reserve University
Cleveland, OH 44106

Joel Verter
George Washington University
Washington, DC

Linda Wright
National Institute of Child Health and Human Development
Bethesda, MD