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DOI: 10.1055/s-2000-9651
Georg Thieme Verlag Stuttgart ·New York
Inhalative Stickstoffmonoxidtherapie bei Frühgeborenen
Inhaled nitric oxide in preterm neonates:Publikationsverlauf
Publikationsdatum:
31. Dezember 2000 (online)
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Zusammenfassung:
Die Therapie der persistierenden pulmonalen Hypertension des Neugeborenen (PPHN) mit inhalativem Stickstoffmonoxid (iNO) zählt nach Veröffentlichung einer Reihe von randomisierten und kontrollierten Studien mittlerweile zu einem etablierten Verfahren in der neonatologischen Intensivmedizin. Ganz anders ist die Situation beim Frühgeborenen, da infolge der Interferenz von Stickstoffmonoxid mit der Thrombozytenaggregation das Risiko von intraventrikulären Blutungen bzw. deren Ausprägungsgrad unter dieser Therapie als risikoreicher eingeschätzt wird. Die bisher vorliegenden Studien bei Frühgeborenen beantworten die Frage nach der Inzidenz von intraventrikulären Blutungen (IVH) nur unzureichend, Endpunkte sind in den meisten Fällen Veränderungen der Oxygenierungsparameter. Mittlerweile konnten zwei größere Studien von iNO bei Frühgeborenen zeigen, dass diese Therapieform nicht mit einer erhöhten Hirnblutungsrate im iNO-Kollektiv assoziiert ist. Weitere randomisierte, kontrollierte Studien zum Einsatz von Stickstoffmonoxid bei Frühgeborenen sind dringend erforderlich um den künftigen Stellenwert dieser Therapieform und deren Indikationen zu determinieren.
According to a number of recently published, randomized controlled trials, treatment of persistent pulmonary hypertension of the newborn (PPHN) by the use of inhaled nitric oxide (iNO) has emerged as an established procedure in neonatology. The situation in premature infants appears to be more complicated than in the term infant. Due to the fact that nitric oxide interferes with platelet aggregation, the risk of intraventricular hemorrhage or its aggravation during iNO therapy is being discussed in a controversial manner. Since most studies are aimed at endpoints like oxygenation parameters, the presently available studies report extremely variable incidences of intraventricular hemorrhages (IVH). Meanwhile two large studies could demonstrate that clinical application of iNO in preterm infants is not associated with an increased incidence of IVH. Further randomized controlled trials of iNO in preterm neonates are highly desirable in order to establish the future role of this therapy and its indications.
Abkürzungen:
BPD Bronchopulmonale Dysplasie
CLD Chronische Lungenerkrankung
ECMO Extrakorporale Membranoxygenierung
FiO2Inspiratorische Sauerstoffkonzentration
iNO Inhalatives Stickstoffmonoxid
IVH Intraventrikuläre Blutung
MAP Mittlerer Atemwegsdruck
OI Oxygenierungsindex
PaO2/PAO2 Arterio-alveolärer Sauerstoffgradient
PPHN Persistierende pulmonale Hypertension des Neugeborenen
ppm Teile per Million
Schlüsselwörter:
Pulmonale Hypertension - inhalatives Stickstoffmonoxid - Frühgeborenes - intraventrikuläre Blutung - Thrombozytenaggregationshemmung - extrakorporale Membranoxygenierung
Key words:
Pulmonary hypertension - inhaled nitric oxide - premature infant - intraventricular hemorrhage - inhibition of platelet aggregation - extracorporeal membrane oxygenation
Literatur
- 01 Amato M, de Roche B, von Muralt G. Persistent pulmonary hypertension in preterm infants. Padiatr Padol. 1986; 21 25-30
- 02 Banks B A, Seri l, Ischiropoulos H, Merrill J, Rychik J, Ballard R A. Changes in oxygenation with inhaled nitric oxide in severe bronchopulmonary dysplasia. Pediatrics. 1999; 103 610-618
- 03 Barefield E S, Karle V A, Phillips J B 3rd, Carlo W A. Inhaled nitric oxide in term infants with hypoxemic respiratory failure. J Pediatr. 1996; 129 279-286
- 04 Bassenge E. Antiplatelet effects of endothelium-derived relaxing factor and nitric oxide donors. Eur Heart J. 1991; 12 12-15
- 05 Chang L Y, Graham J A, Miller F J, Ospital J J, Crapo J D. Effects of subchronic inhalation of low concentrations of nitrogen dioxide. I. The proximal alveolar region of juvenile and adult rats. Toxicol Appl Pharmacol. 1986; 83 45-61
- 06 Cheung P Y, Salas E, Etches P C, Phillipos E, Schulz R, Radomski M W. Inhaled nitric oxide and inhibition of platelet aggregation in critically ill neonates. Lancet. 1998; 351 1181-1182
- 07 Cheung P Y, Peliowski A, Robertson C MT. The outcome of very low birth weight neonates (≤ 1500 g) rescued by inhaled nitric oxide: neurodevelopment in early childhood. J Pediatr. 1998; 133 735-739
- 08 Christou H, Magnani B, Morse D S, Allred E N, Van Marter L J, Wessel D L, Kourembanas S. Inhaled nitric oxide does not affect adenosine 5′-diphosphate-dependent platelet activation in infants with persistent pulmonary hypertension of the newborn. Pediatrics. 1998; 102 1390-1393
- 09 Crow J P, Beckman J S. The role of peroxynitrite in nitric oxide-mediated toxicity. Curr Top Microbiol Immunol. 1995; 196 57-73
- 10 Davidson D, Barefield E S, Kattwinkel J, Dudell G, Damask M, Straube R, Rhines J, Chang C T. Inhaled nitric oxide for the early treatment of persistent pulmonary hypertension of the term newborn: a randomized, double-masked, placebo-controlled, dose-response, multicentre study. The I-NO/PPHN Study Group. Pediatrics. 1998; 101 325-334
- 11 Day R W, Lynch J M, White K S, Ward R M. Acute response to inhaled nitric oxide in newborns with respiratory failure and pulmonary hypertension. Pediatrics. 1996; 98 698-705
- 12 Finer N N, Barrington K J. Nitric oxide in respiratory failure in the newborn infant. Semin Perinatol. 1997; 21 426-440
- 13 George T N, Johnson K J, Bates J N, Segar J L. The effect of inhaled nitric oxide on bleeding time and platelet aggregation in neonates. J Pediatr. 1998; 132 731-734
- 14 Gessler P, Nebe T, Birle A, Mueller W, Kachel W. A new side effect of inhaled nitric oxide in neonates and infants with pulmonary hypertension: functional impairment of the neutrophil respiratory burst. Intensive Care Med. 1996; 22 252-258
- 15 Gommers D, Hartog A, van't Veen A, Lachmann B. Improved oxygenation by nitric oxide is enhanced by prior reaeration with surfactant, rather than positive end-expiratory pressure, in lung-lavaged rabbits. Crit Care Med. 1997; 25 1868-1873
- 16 Hallman M, Bry K, Turbow R, Waffarn F, Lappalainen U. Pulmonary toxicity associated with nitric oxide in term infants with severe respiratory failure. J Pediatr. 1998; 132 827-829
- 17 Hoehn T, Krause M, Hentschel R. High-frequency ventilation augments the effect of inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Eur Respir J. 1998; 11 234-238
- 18 Hoehn T, Krause M. Synergistic effect of high-frequency ventilation and inhaled nitric oxide in the treatment of hypoxemic pulmonary failure in infancy. Pediatr Pulmonol. 1998; 26 228-230
- 19 Hoehn T, Huebner J, Paboura E, Krause M, Leititis J U. Effect of therapeutic concentrations of nitric oxide (NO) upon bacterial growth in vitro. Crit Care Med. 1998; 26 1857-1862
- 20 Hogman M, Frostell C, Arnberg H, Hedenstierna G. Bleeding time prolongation and NO inhalation. Lancet. 1993; 341 1664-1665
- 21 Horstman D J, Frank D U, Rich G F. Prolonged inhaled NO attenuates hypoxic, but not monocrotaline-induced, pulmonary vascular remodeling in rats. Anesth Analg. 1998; 86 74-81
- 22 Kinsella J P, Neish S R, Shaffer E, Abman S H. Low-dose inhalation nitric oxide in persistent pulmonary hypertension of the newborn. Lancet. 1992; 340 819-820
- 23 Kinsella J P, Truog W E, Walsh W F, Goldberg R N, Bancalari E, Mayock D E, Redding G J, deLemos R A, Sardesai S, McCurnin D C, Yoder B A, Moreland S G, Cutter G R, Abman S H. Randomized, multicentre trial of inhaled nitric oxide and high-frequency oscillatory ventilation in severe persistent pulmonary hypertension of the newborn (PPHN). J Pediatr. 1997; 131 55-62
- 24 Kinsella J P, Walsh W F, Bose C L, Gerstmann D R, Labella J J, Sardesai S, Walsh-Sukys M C, McCaffrey M J, Cornfield D N, Bhutani V K, Cutter G R, Baier M, Abman S H. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial. Lancet. 1999; 354 1061-1065
- 25 The Franco-Belgium Collaborative NO Trial Group. Early compared with delayed inhaled nitric oxide in moderately hypoxaemic neonates with respiratory failure: a randomised controlled trial. Lancet. 1999; 354 1066-1071
- 26 Mercier J C, Lacaze T, Storme L, Roze J C, Dinh-Xuan A T, Dehan M. Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure. French Paediatric Study Group of Inhaled NO. Eur J Pediatr. 1998; 157 747-52
- 27 Peliowski A, Finer N N, Etches P C, Tierney A J, Ryan C A. Inhaled nitric oxide for premature infants after prolonged rupture of the membranes. J Pediatr. 1995; 126 450-453
- 28 Putensen C, Räsänen J, Lopez F A, Downs J B. Continuous positive airway pressure modulates effect of inhaled nitric oxide on the ventilation-perfusion distribution in canine lung injury. Chest. 1994; 106 1563-1569
- 29 Putensen C, Räsänen J, Downs J B. Effect of endogenous and inhaled nitric oxide on the ventilation-perfusion relationships in oleic-acid lung injury. Am J Resp Crit Care Med. 1994; 150 330-336
- 30 Puybasset L, Rouby J-J, Mourgeon E, Cluzel P, Souhil Z, Law-Koune J-D, Stewart T, Devilliers C, Lu Q, Roche S, Kalfon P, Vicaut E, Viars P. Factors influencing cardiopulmonary effects of inhaled nitric oxide in acute respiratory failure. Am J Resp Crit Care Med. 1995; 152 318-328
- 31 Roberts J D, Polaner D M, Lang P, Zapol W M. Inhaled nitric oxide in persistent pulmonary hypertension of the newborn. Lancet. 1992; 340 818-819
- 32 Roberts J D, Fineman J R, Morin F C 3rd, Shaul P W, Rimar S, Schreiber M D, Polin R A, Zwass M S, Zayek M M, Gross I, Heymann M A, Zapol W M. Inhaled nitric oxide and persistent pulmonary hypertension ofthe newborn. N Engl J Med. 1997; 336 605-610
- 33 Samarna C M, Diaby M, Fellahi J L, Mdhafar A, Eyraud D, Arock M, Guillosson J J, Coriat P, Rouby J J. Inhibition of platelet aggregation by inhaled nitric oxide in patients with acute respiratory distress syndrome. Anesthesiology. 1995; 83 56-65
- 34 Sasse S, Kribs A, Vierzig A, Roth B. A staged protocol for the treatment of persistent pulmonary hypertension of the newborn. Klin Pädiatr. 1997; 209 301-307
- 35 Saugstad O D. Inhaled nitric oxide for preterm infants - still an experimental therapy. Lancet. 1999; 354 1047-1048
- 36 Skimming J W, Bender K A, Hutchison A A, Drummond W H. Nitric oxide inhalation in infants with respiratory distress syndrome. J Pediatr. 1997; 130 225-230
- 37 Stopfkuchen H. Pathophysiologic principles relevant for therapeutic procedures in persistent pulmonary hypertension of the newborn. Klin Pädiatr. 1995; 207 63-67
- 38 Subhedar N V, Ryan S W, Shaw N J. Open randomised controlled trial of inhaled nitric oxide and early dexamethasone in high risk preterm infants. Arch Dis Child Fetal Neonatal Ed. 1997; 77 F185-F190
- 39 The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. N Engl J Med. 1997; 336 597-604
- 40 The Neonatal Inhaled Nitric Oxide Study Group. Inhaled nitric oxide and hypoxic respiratory failure in infants with congenital diaphragmatic hernia. Pediatrics. 1997; 99 838-845
- 41 van Meurs K P, Rhine W D, Asselin J M, Durand D J. Response of premature infants with severe respiratory failure to inhaled nitric oxide. Preemie NO Collaborative Group. Pediatr Pulmonol. 1997; 24 319-323
- 42 Varela A F, Runge A, Ignano L J, Chandhuri G. Nitric oxide and prostacyclin inhibit fetal platelet aggregation: a response similar to that observed in adults. Am J Obstet Gynecol. 1992; 167 1599-1604
- 43 Watchko J F. Persistent pulmonary hypertension in a very low birthweight preterm infant. Clin Pediatr. 1985; 24 592-595
- 44 Wessel D L, Adatia I, Van Marter L J, Thompson J E, Kane J W, Stark A R, Kourembanas S. Improved Oxygenation in a Randomized Trial of Inhaled Nitric Oxide for Persistent Pulmonary Hypertension of the Newborn. Pediatrics. 1997; 100 E7
Dr. med. Thomas Hoehn
Klinik für Neonatologie Charité, Campus Virchow-Klinikum
Augustenburger Platz 1
13344 Berlin
Telefon: Tel. 030-450 66413
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