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Expert Opinion on Investigational Drugs Volume 4, 1995 - Issue 10
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Research Article

Section Review Pulmonary-Allergy, Dermatological, Gastrointestinal & Arthritis: Recent developments in inhaled nitric oxide therapy

Maurice Beghetti Cardiology and Critical Care Medicine, The Hospital For Sick Children, Department of Paediatrics, University of Toronto, Canada
&
Ian Adatia Cardiology and Critical Care Medicine, The Hospital For Sick Children, Department of Paediatrics, University of Toronto, Canada
Pages 985-995 | Published online: 03 Mar 2008

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  • Excellent study showing that the expression of endothelial nitric oxide synthase is decreased in patients with plexogenic pulmonary arteriopathy and patients with secondary pulmonary hypertension compared to controls. There is an inverse correlation between the expression of the enzyme and the severity of the morphologic lesions, as well as the total pulmonary vascular resistance in plexo-genic arteriopathy.
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  • Selective pulmonary vasodilation associated with increased left ventricular end diastolic pressures.
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  • Selective pulmonary vasodilation associated with increased left ventricular end diastolic pressures. A good discussion of the possible mechanisms,
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  • Effects of nitric oxide in young patients with end-stage congenital heart disease.
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  • GATECEL C, MEBAZAA A, KONG R, GUINARD N, KERMAR-REC N, MATEO J, PAYEN D: Inhaled nitric oxide improves hepatic tissue oxygenation in right ventricular failure: value of hepatic venous oxygen saturation monitoring. Anesthesiology (1995) 82:588–590.
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  • Confirms the sensitivity of children with congenital heart disease and an elevated pulmonary vascular resistance to nitric oxide.
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  • Review describing the role of nitric oxide in asthma.
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  • Seventeen patients with post-operative pulmonary hypertensive crises refractory to conventional treatment received 20 ppm inhaled nitric oxide. Nitric oxide reduced pulmonary arterial pressure by 34% without changing systemic pressure but with an increase in mixed venous and systemic arterial saturation. This suggest that if right ventricular output is limited by pulmonary vascular resistance, nitric oxide may improve systemic perfusion. This contrasts with studies in patients with mild pulmonary hypertension.
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  • Good demonstration of the rebound effect after prolonged treatment.
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  • Careful and thorough evaluation of inhaled nitric oxide in twenty-three patients referred for ECMO. They observed that patients with echocardiographic evidence of pulmonary hypertension were more likely to respond to nitric oxide and that doses between 5 and 80 ppm were equally effective.
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  • KINSELLA JP, ABMAN SH: Recent developments in the pathophysiology and treatment of persistent pulmo-nary hypertension of the new-born. J. Pediatr. (1995) 126(6):853–864.
  • Extensive review of the recent development of the pathophysiology, and treatment of PPHN, especially the effect, success and failure, of inhaled nitric oxide in this heterogeneous disease.
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  • STEINHORN RH, MILLARD SL, MORIN FC: Persistent pulomonary hypertension of the new-born. Clin. Perinatol. (1995) 22(2):405–428.
  • Review of the role of nitric oxide in the pathophysiology and treatment of PPHN.
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  • Up to date description of the role of nitric oxide in the new-born transitional circulation.
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  • Lung tissues of new-born pigs were immunostained with a mono-clonal antibody to endothelial nitric oxide synthase. The greatest expression was seen at two to three days of age.
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  • In vitro study showing that there is a direct and reversible inhibition of nitric oxide synthase by nitric oxide, suggesting a feedback mechanism in vivo. This could be responsible for the rebound pulmonary hypertension noted when prolonged inhaled nitric oxide treatment is stopped abruptly.
  • ASSREUY J, CUNHA FQ, HEW FY, MONCADA S: Feedback Inhibition of nitric oxide synthase activity by nitric oxide. Br. J. Pharmacol. (1993) 108:833–837.
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  • BIGATELLO LM, HURFORD WE, KACMAREK RM, ROBERTS JD, ZAPOL WM: Prolonged administration of low con-centrations of nitric oxide in patients with severe adult respiratory distress syndrome. Anesthesiology (1994) 80:761–770.
  • Careful analysis of inhaled nitric oxide in ARDS. The authors suggest that the effective dose may change with time.
  • YOUNG JD, BRAMPTON WJ, KNIGHTON JD, FINFER 5:Inhaled nitric oxide in acute respiratory failure in adults. Br.]. Anaesthesiol. (1994) 73:499–502.
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  • A good discussion of the advantages of alveolar recruitment with PEEP when using nitric oxide.
  • FIEROBE L, BRUNET F, DHAINAUT J-F, MONCHI M, BEL- GIRTH M, MIRA J-P, DALL'AVA-SANTUCCI J, DINH-XUAN AT: Effect of inhaled nitric oxide on right ventricular function in adult respiratory distress syndrome. Am. J. Respir. Crit. Care Med. (1995) 151:1414–1419.
  • Study of the effect of 5 ppm inhaled nitric oxide for fifteen minutes on RV function in thirteen patients with ARDS.
  • ABMAN SH, GRIEBEL JL, PARKER DK, SCHMIDT JM, SWAN-TON D, KINSELLA JP: Acute effects of inhaled nitric oxide In children with severe hypoxemic respiratory failure. Pediatr. (1994) 124:881–884.
  • Seventeen children with respiratory failure inhaled 20 ppm nitric oxide for thirty minutes. Fifteen patients received prolonged therapy. It is demonstrated that nitric oxide may be useful in this age group as well as adults and neonates.
  • PAYEN DM, GATECEL C, PLAISANCE P: Almitrine effecton nitric oxide inhalation in adult respiratory distress syndrome. lancet (1993) 341(June 26):1664.
  • PUYBASSET L, STEWART T, ROUBY JJ, CLUZEL P, MOUR- GEON E, BELIN MF, ARTHAUD M, LANDAULT C, VIARS P:Inhaled nitric oxide reverses the increase in pulmonary vascular resistance induced by permissive hypercapnia In patients with acute respiratory distress syndrome. Anesthesiology (1994) 80:1254–1267.
  • The authors suggest that both nitric oxide and permissive hypercap-nia can be employed to minimise barotrauma.
  • KARAMANOUKLAN HL, GLICK PL, WILCOX DT, ROSSMAN JE, HOLM BA, MORIN FC: Pathophysiology of congenital diaphragmatic hernia VM: Inhaled nitric oxide re-quires exogenous surfactant therapy in the lamb model of congenital diaphragmatic hernia. J. Pediatr. Surg. (1995) 30(1):1–4.
  • The authors assessed the effect of inhaled nitric oxide on gas exchange, acid-base balance and pulmonary artery pressure in a lamb model of congenital diaphragmatic hernia. Inhaled nitric oxide did not improve oxygenation or decrease pulmonary pressure in control lambs but was effective when surfactant was given to the lambs.
  • LEACH C, MORIN F, FUHRMAN B, HERNAN L, PAPO M, STEINHORN D, STEINHORN R: Efficacy and pharmaco-kinetics of nitric oxide inhalation during partial liquid ventilation with perflubron (liquivent®). Pediatr. Res. (1994) 35:394A.
  • WILCOX D, GLICK P, KARAMANOUKIAN H, MORIN F, FUHRMAN B, LEACH C: Perfluorocarbon associated gas exchange and nitric oxide in the lamb congenital dia-phragmatic hernia modeL Pediatr. Res. (1994) 35:260A.
  • ICHINOSE F, ADAM C, HURFORD WE, ZAPOL WM: Pro-longed pulmonary vasodilator action of inhaled nitric oxide by Zaprinast in awake lambs./ Appl. Physiol. (1995) 78(4):1288–1295.
  • An animal study demonstrating that simultaneous infusion of zapri-nast, a phosphodiesterase inhibitor, with inhaled nitric oxide causes a further reduction in PVR and prolongs the action of inhaled nitric oxide. Plasma concentrations of cGMP were increased by zaprinast during nitric oxide inhalation.
  • STEINHORN R, THUSU K, RUSSEL J: The cGMP phosphodi-esterase inhibitor zaprinast enhances the effect of nitric oxide in new-born lambs with persistent pulmonary hypertension. Pediatr. Res. (1994) 35:89A.
  • ROSSAINT R, GERLACH H, SCHMIDT-RUHNKE H, PAPPERT D, LEWANDOWSKI K, STEUDEL W, FALKE K: Efficacy of Inhaled nitric oxide in patients with severe ARDS. Chest (1995) 107:1107–1115.
  • Retrospective review of eighty-seven patients with ARDS. Thirty of these inhaled low concentrations of nitric oxide for more than forty-eight hours. They show a beneficial effect of inhaled nitric oxide in most patients. Survival rates in patients receiving nitric oxide did not differ from untreated patients.
  • WATKINS DN, JENKINS IR, RANKIN JM, CLARKE GM: In-haled nitric oxide in severe acute respiratory failure - its use in intensive care and description of a delivery system. Anaesth. Inkms. Care (1993) 21:861–875.
  • PETROS AJ, COX P, BOHN D: A simple method for monitoring the concentration of inhaled nitric oxide. Anaesthesia (1994) 49:317–319.
  • MILLER OI, CELERMAJER DS, DEANFIELD JE, MACRAE DJ:Guidelines for the safe administration of inhaled nitric oxide. Arch. Dis. Child. (1994) 70:F47–F49.
  • FOUBERT L, FLEMING B, LATIMER R, JONAS M, ODURO A,BORLAND C, HIGENBOTTAM T: Safety guidelines for use of nitric oxide. lancet (1992) 339:1615–1616.
  • WENNMALM A, BENTHIN G, EDLUND A, JUNGERSTEN L,JENSEN NK, LUNDIN S, WES 1.1-bLT UN, PETERRSON A-S, WAAGSTEIN F: Metabolism and excretion of nitric oxide in humans. Circ. Res. (1993) 73:1121–1127.
  • TIBBALLS J, HOCHMANN M, CARTER B, OSBORNE A: Anappraisal of techniques for administration of gaseous nitric oxide. Anaesth. Intens. Care (1993) 21(6)844–847.
  • STENQVIST O, KJELLTOFT B, LUNDIN S: Evaluation of a new system for ventilatory administration of nitric oxide. Acta Anaesthesiol. Scand. (1993) 37:687–691.
  • WESSEL DL, ADATIA I, THOMPSON JE, HICKEY PR: Deliv-ery and monitoring of inhaled nitric oxide in patients with pulmonary hypertension. Crit. Care Med. (1994) 22 :930–938 .
  • Comprehensive review of the delivery and monitoring of inhaled nitric oxide in a large group of patients.
  • BETIT P, ADATIA I, BENJAMIN P, THOMPSON JE, WESSEL DL: Inhaled nitric oxide: evaluation of a continuous titration delivery technique developed for infant me-chanical ventilation and transport. Resp. Care (1995) 40:706–715.
  • KINSELLA J, SCMIDT J, GRIEBEL J, ABMAN S: Inhaled nitric oxide treatment for stabilization and emergency medi-cal transport of critically ill new-born infants. Pediatrics (1995) 95:773–776.
  • ZAPOL WM, RIMAR S, GILDS N, MARLETTA M, BOSKEN CH: NHLBI Workshop Summary: nitric oxide and the lung. Am. J. Respir. Crit. Care Med. (1994) 149:1375–1380.
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