Rg. Kilbourn et al., N-G-METHYL-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, REVERSES INTERLEUKIN-2-INDUCED HYPOTENSION, Critical care medicine, 23(6), 1995, pp. 1018-1024
To evaluate the role of N-G-methyl-L-arginine as a modulator of the hy
perdynamic shock induced by the administration of interleukin-2 (IL-2)
. Design: A prospective, pilot clinical study. Setting: Intensive care
unit of a tertiary care center. Patients: Three sequential patients w
ith metastatic renal cell carcinoma who developed hypotension during t
heir first course of treatment with high-dose IL-2 (18 x 10(6) IU/m(2)
/day by continuous infusion for 5 days). Interventions: Upon developin
g hypotension during their subsequent therapy with IL-2, patients were
administered 12 mg/kg of N-G-methyl-L-arginine. Thereafter, a dose of
4 mg/kg was given every 4 hrs, as needed, to maintain the systolic bl
ood pressure above 100 mm Hg. Measurements and Main Results: Invasive
hemodynamic monitoring was instituted before the initiation of treatme
nt with IL-2. Differences noted before, and 15 mim after, the administ
ration of N-G-methyl-L-arginine were analyzed using the paired t-test.
N-G-methyl-L arginine (12 mg/kg) induced a significant antihypotensiv
e effect (mean blood pressure increased from 87 +/- 4 to 121 +/- 7 mm
Hg), accompanied by an increase of the systemic vascular resistance (5
49 +/- 51 to 860 +/- 167 dyne sec/cm(5)) and pulmonary vascular resist
ance (81 +/- 16 to 117 +/- 29 dyne sec/cm(6)). A decrease in the cardi
ac index was also documented (4.5 +/- 0.5 to 3.6 +/- 0.3 L/min/m(2)),
No significant changes in pulmonary artery occlusion and central venou
s pressures were observed, Maintenance doses of 4 mg/kg of N-G-methyl-
L-arginine induced similar hemodynamic results, although the duration
of the antihypotensive effect of N-G-methyl-l-arginine decreased with
sequential doses. Conclusions: The hemodynamic effects induced by IL-2
administration are reversed by N-G-methyl-L-arginine, a nitric oxide
synthesis inhibitor. These results provide evidence for the biological
activity of N-G-methyl-L-arginine when administered alone to hypotens
ive patients. While no adverse effects were observed in this prelimina
ry study, issues of toxicity and effectiveness need to be defined furt
her in formal clinical trials. N-G-methyl-L-arginine may play a therap
eutic role in the modulation of the extreme vasodilation induced by cy
tokine administration or in septic shock.