Just Say No to iNO in Preterms—Really?

Lakshminrusimha, Satyanarayana; Kinsella, John P.; Krishnan, Usha; Meurs, Krisa P. Van; Edwards, Erika M.; Bhatt, Dilip R.; Chandrasekharan, Praveen; Oei, Ju Lee; Manja, Veena; Ramanathan, Rangasamy

doi:10.1016/j.jpeds.2019.10.063

Cited by 14 publications

(16 citation statements)

References 61 publications

(78 reference statements)

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“…At SpO 2 of 93–97% an increase in both PaO 2 and PAO 2 were necessary to achieve optimal decrease in PVR ( Figure 3 ). With the high prevalence of PHT among extremely preterm infants, it is critical to understand the role of PAO 2 in regulating PVR [ 33 ]. Kinsella et al evaluated the pulmonary vasodilator effect of iNO, oxygen and lung distension on developing pulmonary circulation [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?

2020

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Oxygen is a pulmonary vasodilator and plays an important role in mediating circulatory transition from fetal to postnatal period. Oxygen tension (PO2) in the alveolus (PAO2) and pulmonary artery (PaO2) are the main factors that influence hypoxic pulmonary vasoconstriction (HPV). Inability to achieve adequate pulmonary vasodilation at birth leads to persistent pulmonary hypertension of the newborn (PPHN). Supplemental oxygen therapy is the mainstay of PPHN management. However, optimal monitoring and targeting of oxygenation to achieve low pulmonary vascular resistance (PVR) and optimizing oxygen delivery to vital organs remains unknown. Noninvasive pulse oximetry measures peripheral saturations (SpO2) and a target range of 91–95% are recommended during acute PPHN management. However, for a given SpO2, there is wide variability in arterial PaO2, especially with variations in hemoglobin type (HbF or HbA due to transfusions), pH and body temperature. This review evaluates the role of alveolar, preductal, postductal, mixed venous PO2, and SpO2 in the management of PPHN. Translational and clinical studies suggest maintaining a PaO2 of 50–80 mmHg decreases PVR and augments pulmonary vasodilator management. Nevertheless, there are no randomized clinical trials evaluating outcomes in PPHN targeting SpO2 or PO2. Also, most critically ill patients have umbilical arterial catheters and postductal PaO2 may not be an accurate assessment of oxygen delivery to vital organs or factors influencing HPV. The mixed venous oxygen tension from umbilical venous catheter blood gas may assess pulmonary arterial PO2 and potentially predict HPV. It is crucial to conduct randomized controlled studies with different PO2/SpO2 target ranges for the management of PPHN and compare outcomes.

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Section: Discussionmentioning

confidence: 99%

How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?

2020

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“…Despite an apparent increase in incidence of early PPHN, only 3–8% of the VLGA population is currently affected by PPHN. In most surveys of VLGA infants, iNO treatment is considerably more common ( 120 ), suggesting heterogeneity of indications for iNO therapy.…”

Section: Management Of Transitional Circulationmentioning

confidence: 99%

Management Practices During Perinatal Respiratory Transition of Very Premature Infants

et al. 2022

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The present review considers some controversial management practices during extremely premature perinatal transition. We focus on perinatal prevention and treatment of respiratory distress syndrome (RDS) in immature infants. New concerns regarding antenatal corticosteroid management have been raised. Many fetuses are only exposed to potential adverse effects of the drug. Hence, the formulation and the dosage may need to be modified. Another challenge is to increase the fraction of the high-risk fetuses that benefit from the drug and to minimize the harmful effects of the drug. On the other hand, boosting anti-inflammatory and anti-microbial properties of surfactant requires further attention. Techniques of prophylactic surfactant administration to extremely immature infants at birth may be further refined. Also, new findings suggest that prophylactic treatment of patent ductus arteriosus (PDA) of a high-risk population rather than later selective closure of PDA may be preferred. The TREOCAPA trial (Prophylactic treatment of the ductus arteriosus in preterm infants by acetaminophen) evaluates, whether early intravenous paracetamol decreases the serious cardiorespiratory consequences following extremely premature birth. Lastly, is inhaled nitric oxide (iNO) used in excess? According to current evidence, iNO treatment of uncomplicated RDS is not indicated. Considerably less than 10% of all very premature infants are affected by early persistence of pulmonary hypertension (PPHN). According to observational studies, effective ventilation combined with early iNO treatment are effective in management of this previously fatal disease. PPHN is associated with prolonged rupture of fetal membranes and birth asphyxia. The lipopolysaccharide (LPS)-induced immunotolerance and hypoxia-reperfusion-induced oxidant stress may inactivate NO-synthetases in pulmonary arterioles and terminal airways. Prospective trials on iNO in the management of PPHN are indicated. Other pulmonary vasodilators may be considered as comparison drugs or adjunctive drugs. The multidisciplinary challenge is to understand the regulation of pregnancy duration and the factors participating the onset of extremely premature preterm deliveries and respiratory adaptation. Basic research aims to identify deficiencies in maternal and fetal tissues that predispose to very preterm births and deteriorate the respiratory adaptation of immature infants. Better understanding on causes and prevention of extremely preterm births would eventually provide effective antenatal and neonatal management practices required for the intact survival.

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“…NO inhalation has been suggested for the treatment of severe persistent pulmonary hypertension of the newborn (Roberts, Polaner, Lang, & Zapol, 1992) as it has been shown to it was shown to rapidly increase systemic oxygenation without causing hypotension. Several guidelines summarize the use of inhalative NO in newborns (Kinsella et al, 2016; Lakshminrusimha et al, 2020). Limitations in the therapy with inhaled NO are not only its short half‐life and possible rebound hypertension after discontinuation.…”

Section: Pediatric Lung Diseasesmentioning

confidence: 99%

“…to it was shown to rapidly increase systemic oxygenation without causing hypotension. Several guidelines summarize the use of inhalative NO in newborns (Kinsella et al, 2016;Lakshminrusimha et al, 2020). Limitations in the therapy with inhaled NO are not only its short half-life and possible rebound hypertension after discontinuation.…”

Section: Pulmonary Fibrosismentioning

confidence: 99%

NO‐sensitive guanylyl cyclase in the lung

Friebe

Englert

2021

British J Pharmacology

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In the late 1960s, several labatories identified guanylyl cyclase (GC) as the cGMP‐producing enzyme. Subsequently, two different types of GC were described that differed in their cellular localization. Primarily found in the cytosol, nitric oxide (NO)‐sensitive guanylyl cyclase (NO‐GC) acts as receptor for the signalling molecule NO, in contrast the membrane‐bound isoenzyme is activated by natriuretic peptides. The lung compared with other tissues exhibits the highest expression of NO‐GC. The enzyme has been purified from lung for biochemical analysis. Although expressed in smooth muscle cells (SMCs) and in pericytes, the function of NO‐GC in lung, especially in pericytes, is still not fully elucidated. However, pharmacological compounds that target NO‐GC are available and have been implemented for the therapy of pulmonary arterial hypertension. In addition, NO‐GC has been suggested as drug target for the therapy of asthma, acute respiratory distress syndrome and pulmonary fibrosis. LINKED ARTICLES This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc

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Just Say No to iNO in Preterms—Really?

Cited by 14 publications

References 61 publications

How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?

How Do We Monitor Oxygenation during the Management of PPHN? Alveolar, Arterial, Mixed Venous Oxygen Tension or Peripheral Saturation?

Management Practices During Perinatal Respiratory Transition of Very Premature Infants

NO‐sensitive guanylyl cyclase in the lung

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