Pulmonary Edema Caused by Inhaled Nitric Oxide Therapy in Two ...

Spirometry results and lung volumes were normal on pulmonary
function testing, and diffusion capacity of the lung for carbon
monoxide was 16% of predicted. Arterial blood gas measures
obtained with the patient breathing oxygen at 3 L/min were as
follows: pH, 7.34; Po 2, 52 mm Hg; and Pco 2, 39 mm Hg. CT of
the chest showed minimal ground-glass opacities.
A left-heart catheterization revealed normal coronary arteries
and left ventricular function. Hemodynamic measurements during
right-heart catheterization are shown in Table 1. The test was
performed while the patient breathed 40% oxygen, and oxygen
saturation was maintained at 90%. During iNO administration
at 40 ppm, severe dyspnea, tachypnea, and tachycardia developed,
and oxygen saturation fell to 85%. Lung auscultation
revealed new bilateral rales. An ECG did not show ischemic
changes. Pulmonary artery wedge pressure and pulmonary artery
pressure remained unchanged. iNO was immediately discontinued,
and sublingual nitroglycerin and IV morphine and furosemide
were administered, with rapid symptomatic improvement.
A chest radiograph obtained after symptomatic
improvement showed mild interstitial edema. The next morning,
epoprostenol infusion was initiated that was tolerated up to
4 ng/kg/min (Table 1). Treatment with epoprostenol was followed
by an IV nitroglycerin infusion up to 80 g/min that was
discontinued because of systemic hypotension. The patient was
discharged home with a continuous subcutaneous infusion of
prostacyclin (UT-15; United Therapeutics; Research Triangle
Park, NC) and has remained symptomatically improved for 6
months.
Case 2
A 57-year-old woman with a 24-year history of CREST syndrome
and a 2-year history of progressive dyspnea on exertion was referred
for acute vasodilator testing. Her medications included nifedipine
and omeprazole and supplemental nasal oxygen at 4 to 5 L/min.
Physical examination revealed facial telangiectasias, few bibasilar
rales on lung auscultation, a prominent right ventricular impulse, an
increased P 2, a holosystolic murmur at the left lower sternal border,
trace ankle edema, and sclerodactyly.
Pulmonary function tests showed a total lung capacity of 52% of
predicted and a diffusion capacity of the lung for carbon monoxide
of 26% of predicted. Oxygen saturation of hemoglobin with the
patient at rest and receiving oxygen supplementation at 4 L/min was
94%. Chest radiography revealed increased markings at the lung
bases and small pleural effusions bilaterally (Fig 1, top). Echocardiography
revealed a peak pulmonary artery pressure of 67 mm Hg
and normal left ventricular function. Hemodynamic measurements
during heart catheterization with the patient breathing 35% oxygen
are shown in Table 1. While receiving iNO at 20 ppm, acute
dyspnea, tachypnea, and increased bilateral rales developed. Oxygen
saturation was maintained at 90% after the fraction of inspired
oxygen was increased to 100% by face mask. Chest radiography
showed increased interstitial markings compatible with pulmonary
edema (Fig 1, middle), but pulmonary artery wedge pressure
remained unchanged. After prompt discontinuation of iNO, IV
morphine and furosemide were administered and symptoms improved
rapidly. A follow-up chest radiograph obtained 7 h after the
episode showed improvement of the interstitial markings (Fig 1,
bottom). The next day, epoprostenol infusion was administered only
up to 2 ng/kg/min, due to systemic hypotension. The patient was
discharged home receiving epoprostenol at 1 ng/kg/min and had a
transient improvement in her dyspnea. She died 4 months later of
intractable right-heart failure. Pathologic examination of the lungs
showed interstitial fibrosis and intimal thickening of pulmonary
arteries, compatible with her diagnosis of CREST syndrome. There
was no evidence of left-heart or pulmonary venous disease.
Discussion
We observed symptoms and signs of acute pulmonary
edema during iNO testing in two patients with severe
PAH associated with the CREST syndrome. No such
reaction developed in 46 other patients with PAH of
different etiologies undergoing vasodilator testing with
iNO or epoprostenol.
Acute pulmonary edema has previously been reported
in patients with scleroderma during short-term8–10 and
Table 1—Hemodynamic Characteristics of the Two Patients at Baseline and During Short-term Vasodilator Testing*
Patient No. Vasodilator
SBP,
mm Hg
PAP,
mm Hg
mPAP,
mm Hg
PVR,
dyne s cm 5
PAWP,
mm Hg CO, L/min
SVR,
dyne s cm 5
1
iNO baseline 119/60 98/37 61 1,054 12 3.64 1,472
iNO, 5 ppm 121/48 88/32 54 755 13 4.34 1,198
iNO, 10 ppm 112/47 87/31 53 798 8 4.51 1,081
iNO, 20 ppm 114/44 87/31 52 818 8 4.30 1,227
iNO, 40 ppm† 120/68 88/30 52 7
Epo baseline 108/38 88/31 53 1,132 5 3.39 1,297
Epo, 3 ng/kg/min 96/52 70/26 43 690 6 4.17 1,208
Epo, 4 ng/kg/min 101/52 74/27 46 701 7 4.45 1,150
2
iNO baseline 110/94 86/34 51 945 12 3.30 2,182
iNO, 5 ppm 98/67 72/25 41 954 10 3.10 1,935
iNO, 10 ppm 90/69 78/29 45 867 11 3.50 1,600
iNO, 20 ppm† 135/73 85/34 51 945 12 3.30 2,109
Epo baseline 105/97 81/30 47 1,020 10 2.90 2,538
Epo, 1 ng/kg/min 97/66 81/47 47 921 9 3.30 1,503
Epo, 2 ng/kg/min 84/59 81/30 47 9
*SBP systemic BP; PAP pulmonary artery pressure; mPAP mean pulmonary artery pressure; PVR pulmonary vascular resistance;
PAWP pulmonary arterial wedge pressure; CO cardiac output; SVR systemic vascular resistance; Epo epoprostenol.
†Dose of iNO at which pulmonary edema occurred.
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CHEST / 121 /2/FEBRUARY, 2002 657