EDITORIAL CORRESPONDENCE Inhaled nitric oxide can cause severe systemic hypotension To the Editor: We read with interest the case report presented by Henrichsen et at) in a letter to the Editor of The Journal, illustrating the risk of systemic hypotension with inhaled nitric oxide (iNO) therapy in patients with left ventricular (LV) dysfunction. Though we do en- tirely support their statement, we believe that other mechanisms than those described may explain the observed hypotensive effect of iNO. A structurally normal heart with severe LV dysfunction and a bi- directional shunt through a patent ductus arteriosus does not sug- gest that systemic perfusion is duct dependent, inasmuch as the shunt is not exclusively unidirectional right to left. Bidirectional shunting usually is explained by a high, near systemic, total pulmo- nary vascular resistance resulting from maladaptation of the pulmonary circulation to the extrauterine life, and perhaps also by reflex pulmonary vasoconstriction induced by severe LV dysfunc- tion, tn patients with increased pulmonary venous pressure caused by LV dysfunction and elevated left atrial pressure, a decrease in pul- monary vascular resistance (induced by iNO) will lead to an increase in pulmonary venous return and hence to an increase in left atrial and LV filling pressure. 2, 3 This increase may not be assumed by a failing left ventricle that is working on the flat portion of the Frank-Starling curve. Accordingly, we believe that, in the patient described, massive vasodilation induced by iNO resulted in further LV failure. Inhaled nitric oxide should be administered with caution to ba- bies with LV dysfunction because pulmonary vasoconstriction may act as a protective mechanism of LV overfilling. Maurice Beghetti, MD Michel Berne,; MD Peter C. Rimensberger, MD Pediatric Cardiology Unit Pediatric Intensive Care Unit H@ital des Enfants, University Hospital of Geneva Geneva 14, Switzerland 9/35/80533 REFERENCES I. Hentichsen T, Goldman AP, Macrae DJ. Inhaled nitric oxide can cause severe systemic hypotension. J Pediatr 1996;129: 183. 2. Lob E, Stamter JS, Hare JM, Loscalzo J, Colucci WS. Cardio- vascular effects of inhaled nitric oxide in patients with left ventricular dysfunction. Circulation 1994;90:2780-5. 3. Adatia I, Perry S, Landzberg M, Moore P, Thompson JE, Wes- sel DL. Inhaled nitric oxide and hemodynamic evaluation of patients with pulmonary hypertension before transplantation. J Am Coil Cardiol 1995;25:1656-64. Granulocyte colony-stimulating factor and neonatal infection To the Editor: I read with interest the article "Granulocyte Colony-stimulating Factor as a Marker for Bacterial Infection of Neonates," by Ken- non et alJ The authors stregsed the specificity of granulocyte col- ony-stimulating factor (G-CSF) for neonatal infection and con- cluded that G-CSF can be used as an early marker of neonatal in- fection. However, I disagree with this view, especially as it pertains to the first few days after birth. In the early neonatal period, especially in the first few days after birth, data on various kinds of laboratory values (i.e., hormones, biochemical parameters, immunologic products, and cytokines) vary considerably, and their average "normal" values difi'er from those measured in later periods. Some of these differences are due to direct stress on the baby during the perinatal period or to map adaptation to the extrauterine environment, causing the activation or suppression of the production of certain substances. Creatine ki- nase and thyroid-stimulating hormone are in this category. Other variations are due to influx from the placenta. Small molecular ma- tennis that cross the placenta raise their concentrations in the infants toward the levels in the mother, lmmunoglobulin G is in this cat- egory. G-CSF is also one of these factors that can cross the placen- ta. 2 The placenta is an organ that produces various cytokines. Under conditions that stimulate production of cytokines, such as chorio- amnionitis or labor, the placenta produces large amounts of cyto- kines and raises their concentration in cord blood, which results in high values of these cytokines in the neonates. High cytokine lev- els have been observed in the healthy neonate with no evidence of clinical infection) Ikeno 4 reported that cord blood G-CSF levels in neonates may be increased in response not only to infection but also to stressed states such as fetal distress and neonatal asphyxia. The elevated level of G-CSF in cord blood persists in the neonate's pe- ripheral blood for several days_ This also seems likely for other cy- tokines. The data contained in the article do not include the G-CSF value in the early neonatal period. The authors did not refer to this point in the discussion, either. The investigators should reconsider the sensitivity of G-CSF to infection in the early neonatal period, when infants are relatively susceptible to infection. Seiji Mizuno, MD Department of Neonatology Toyota Memorial Hospital Toyota, Aichi 471 Japan 9/35/80532 8 4 4 May 1997 The Journal of Pediatrics
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