The incidence and pathogenesis of cardiopulmonary deterioration after abrupt withdrawal of inhaled nitric oxide

We studied the effect of abrupt discontinuation of inhaled nitric oxide (iN O) in patients receiving this drug for treatment of acute hypoxemic respira tory 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 i n Pa-O2 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 parameter s. For the group, discontinuation of iNO caused a significant decrease in P ao(2), arterial and mixed venous oxygen saturation, and ratio of Pa-2, to f raction of inspired oxygen (FIO2). Three patterns of response were observed . Eight of 31 (25.8%) patients had minimal changes in oxygenation or hemody namics, suggesting no need for ongoing therapy. Fifteen of 31 (48%) patient s had worsened gas exchange as a predominant response. Eight of 31 patients exhibited hemodynamic collapse, defined as > 20% fall in cardiac output an d/or mean arterial blood pressure. In this last subgroup, the pattern of ca rdiovascular changes suggested that this response arose from an acute incre ase in right ventricular afterload, and was not a consequence of gas-exchan ge abnormalities. In all cases, reinstitution of iNO promptly reversed wors ened hemodynamics and gas exchange. Independent factors associated with an increased risk of cardiovascular collapse included multisystem organ failur e, older age, and initial blood pressure increase in response to iNO; a sma ller change in the ratio of Pa-O2 to FIO2 with initiation of iNO therapy al so tended to correlate with this phenomenon. We conclude that careful and m onitored discontinuation of iNO in patients with AHRF will identify substan tial fractions of patients who are either receiving no benefit from this th erapy or who require iNO to maintain an adequate circulation and are theref ore at risk for adverse outcome with transport or inadvertent discontinuati on of iNO. Future trials of iNO should recognize this complication of such therapy and include assessments for it.