J. Christenson et al., The incidence and pathogenesis of cardiopulmonary deterioration after abrupt withdrawal of inhaled nitric oxide, AM J R CRIT, 161(5), 2000, pp. 1443-1449
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.