Nitric oxide synthase inhibition by L-NAME in leukocytopenic patients with severe septic shock.
OBJECTIVE
To investigate the effects of nitric oxide synthase inhibition by NG-nitro-L-arginine methyl ester (L-NAME) on hemodynamics and outcome in leukocytopenic (< 1000/microliter) patients with severe septic shock requiring strong vasopressor support.


METHODS
Prospective clinical study.


METHODS
Medical intensive care unit.


METHODS
10 patients with hematologic malignancies in chemotherapy-induced leukocytopenia with severe septic shock and high-dose vasopressor requirement.


METHODS
Continuous intravenous infusion of L-NAME (0.3 mg/ kg per hour) for a study period of 24 h with prolongation for up to 96 h according to individual requirements.


RESULTS
Compared to baseline values, an increase in mean arterial pressure (p = 0.0021), systemic vascular resistance (p = 0.0001), and left ventricular stroke work index (p = 0.023) with a concomitant decrease in vasopressor requirement (p < 0.05) was observed during the first 24 h of L-NAME treatment. Cardiac output data were unchanged during the study period (p = 0.49). L-NAME was tapered off in five patients who again became responsive to vasopressor medication. Two patients survived the episode of septic shock and vasoactive medication was stopped.


CONCLUSIONS
The data demonstrate that inhibition of nitric oxide synthase may be beneficial for the treatment of severe septic shock in leukocytopenic patients as indicated by an increase in systemic vascular resistance, mean arterial pressure, and left ventricular stroke work index.
Kiehl
M G
MG
Department of Internal Medicine, University of Muenster, Germany.
Ostermann
H
H
Meyer
J
J
Kienast
J
J
D000328:Adult; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D019337:Hematologic Neoplasms / Q000150:complications / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced / Q000150:complications*; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000209:etiology; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester