Table 1 Highest level of evidence so far available about the iNO potential for clinical applications and highlights on research gaps before trialing specific area of research

PPHN

PAP, PaO₂/FiO₂

–

–

–

iNO reduces PAP and improves oxygenation [198]

Mortality

–

–

–

iNO reduces mortality [198]

ARDS

PaO₂/FiO₂

–

–

–

iNO is superior to control group [190,191,192,193]

Mortality

–

–

n.s [190, 193]

n.a

Pulmonary Arterial Hypertension

PAP

–

–

–

iNO improves pulmonary hemodynamics [189]

Cardiac arrest

Brain and heart function

iNO prevents neurological and cardiac dysfunction [134]

–

n.s. [137]

n.a

Mortality

iNO reduces mortality [135]

–

iNO reduces mortality [137]

n.a

Myocardial infarction

Infarct size after reperfusion

iNO decreases infarction size [144]

iNO decreases infarction size [145]

–

n.s [146]

Stroke

Infarct size

iNO reduces infarct size [111,112,113]

n.a

n.a

n.a

SAH

Brain ischemia

iNO reduces brain-edema formation and neuronal loss [125]

n.a

n.a

n.a

Mortality

iNO reduces mortality and improves neurological outcome [125]

n.a

n.a

n.a

TBI

Secondary brain damage

iNO reduces secondary brain injury [131]

iNO reduces secondary brain injury [132, 133]

n.a

n.a

Hemolysis

Vasoconstriction

–

iNO prevents hemolysis induced vasoconstriction [149]

n.a

n.a

AKI

–

iNO prevents hemolysis induced AKI [149]

n.a

n.a

CPB-associated hemolysis

AKI

–

–

–

iNO reduces CBP-associated AKI [166]

Transfusion associated hemolysis

Pulmonary vasoconstriction

–

iNO prevents old blood cell induced vasoconstriction [173]

iNO prevents old blood cell induced vasoconstriction (volunteers) [172]

n.a

Artificial blood hemolysis

Vasoconstriction

–

iNO prevents HBOC-induced vasoconstriction [152]

n.a

n.a

Organ transplantation

IR injury

iNO during ex vivo lung perfusion reduces lungs wet-to-dry ratio [99]

n.a

iNO improves liver function in orthotopic liver transplantation [103]

n.a