Tissue oxygenation and hemodynamic response to NO synthase inhibition in septic shock.
The objective of the study was to evaluate the tissue oxygenation and hemodynamic effects of NOS inhibition in clinical severe septic shock. Eight patients with septic shock refractory to volume loading and high level of adrenergic support were prospectively enrolled in the study. Increasing doses of NOS inhibitors [N(G)-nitro-L-arginine-methyl ester (L-NAME) or N(G)-monomethyl-L-arginine (L-NMMA)] were administered as i.v. bolus until a peak effect = 10 mmHg on mean blood pressure was obtained or until side effects occurred. If deemed clinically appropriate, a continuous infusion of L-NAME was instituted and adrenergic support weaning attempted. The bolus administration of NOS inhibitors transiently increased mean blood pressure by 10 mm Hg in all patients. Seven out of eight patients received an L-NAME infusion, associated over 24 h with a progressive decline in cardiac index (P < 0.001) and an increase in systemic vascular resistance (P < 0.01). Partial or total adrenergic support weaning was rapidly possible in 6/8 patients. Oxygen transport decreased (P < 0.001), but oxygen consumption remained unchanged in those patients in whom it could be measured by indirect calorimetry (5/8). Blood lactate and the difference between tonometric gastric and arterial PCO2 remained unchanged. There were 4/8 ICU survivors. We conclude that nitric oxide synthase inhibition in severe septic shock was followed with a progressive correction of the vasoplegic hemodynamic disturbances with finally normalization of cardiac output and systemic vascular resistances without any demonstrable deterioration in tissue oxygenation.
Broccard
A
A
Department of Medicine, University Hospital, Lausanne, Switzerland.
Hurni
J M
JM
Eckert
P
P
Liaudet
L
L
Schaller
M D
MD
Lazor
R
R
Perret
C
C
Feihl
F
F
D000322:Adrenergic Agonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D015687:Cell Hypoxia / Q000187:drug effects*; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010101:Oxygen Consumption / Q000187:drug effects; D011446:Prospective Studies; D012772:Shock, Septic / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D016896:Treatment Outcome; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000322:Adrenergic Agonists; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester