The Incidence and Pathogenesis of Cardiopulmonary Deterioration after Abrupt Withdrawal of Inhaled Nitric Oxide

Abstract

We studied the effect of abrupt discontinuation of inhaled nitric oxide (iNO) in patients receiving this drug for treatment of acute hypoxemic respiratory failure (AHRF), in order to determine the need for continued therapy, the incidence and nature of adverse events, and the risk factors predicting these adverse events. Thirty-one patients who showed an initial increase in Pa(O(2)) of > 20 mm Hg in response to iNO underwent a discontinuation trial at 10 to 30 h after beginning iNO. Indwelling arterial and pulmonary artery catheters facilitated monitoring of hemodynamic and gas-exchange parameters. For the group, discontinuation of iNO caused a significant decrease in Pa(O2 ), arterial and mixed venous oxygen saturation, and ratio of Pa(O(2)) to fraction of inspired oxygen (FI(O(2))). Three patterns of response were observed. Eight of 31 (25.8%) patients had minimal changes in oxygenation or hemodynamics, suggesting no need for ongoing therapy. Fifteen of 31 (48%) patients had worsened gas exchange as a predominant response. Eight of 31 patients exhibited hemodynamic collapse, defined as > 20% fall in cardiac output and/or mean arterial blood pressure. In this last subgroup, the pattern of cardiovascular changes suggested that this response arose from an acute increase in right ventricular afterload, and was not a consequence of gas-exchange abnormalities. In all cases, reinstitution of iNO promptly reversed worsened hemodynamics and gas exchange. Independent factors associated with an increased risk of cardiovascular collapse included multisystem organ failure, older age, and initial blood pressure increase in response to iNO; a smaller change in the ratio of Pa(O(2)) to FI(O(2)) with initiation of iNO therapy also tended to correlate with this phenomenon. We conclude that careful and monitored discontinuation of iNO in patients with AHRF will identify substantial fractions of patients who are either receiving no benefit from this therapy or who require iNO to maintain an adequate circulation and are therefore at risk for adverse outcome with transport or inadvertent discontinuation of iNO. Future trials of iNO should recognize this complication of such therapy and include assessments for it.

S -nitrosothiol repletion by an inhaled gas regulates pulmonary function

“…One of the most frequent complications of inhaled NO therapy is ''rebound'' (21). On discontinuing the drug, PAP may rebound to a level higher than baseline, perhaps because of inhibition of endothelial NOS.…”

“…The gas is preferentially delivered to well-ventilated areas of the lung, thereby coupling ventilation (V) to perfusion (Q), and it acts as a selective pulmonary vasodilator (16). However, inhaled NO therapy has some drawbacks: impairment of renal function (17), methemoglobinemia (18), left heart failure (19), and perhaps intraventricular cerebral hemorrhage (20) can complicate therapy, and a ''rebound'' increase in pulmonary artery pressure (PAP) on discontinuing the gas is common and may result in cardiovascular collapse (21). In addition, the usage of NO gas has been tempered by a worrisome increase in morbidity and decrease in ventilator-free survival (the percentage of patients alive and off ventilatory support) in a large multicenter trial of patients with acute lung injury and by similar concerns raised in post hoc analyses of other studies (17,22).…”

Inhalative and intravenous stimulation of soluble guanylate cyclase reduces pulmonary vascular resistance and increases cardiac output in experimental septic shock

“…However, iNO had an additional positive effect on oxygenation. Considering the adverse effect of discontinuing iNO, which was observed in the majority of patients by Christenson et al (27), there remain doubts that septic patients benefit from ventilation with iNO in the long term. Stimulation of sGC with drugs, such as BAY 41-8543, represents an alternative treatment to iNO.…”

En kvinne i 70-årene med dekompensert hjertesvikt under operasjon

“…involvere nedregulering av endogent produsert NO. En kontrollert reduksjon av inhalert NO anbefales derfor (10,11). Dette ble gjort med hell hos vår pasient.…”