February 1994

Detrimental Hemodynamic Effects of Nitric Oxide Synthase Inhibition in Septic Shock

Author Affiliations

From the Department of Surgery, Critical Care Service, Brooke Army Medical Center (Drs Robertson, Offner, and Ciceri) and the US Army Institute of Surgical Research (Drs Becker and Pruitt), Fort Sam Houston, Tex.; Dr Robertson is now with the Division of Pediatric Surgery, New England Medical Center, Boston, Mass.

Arch Surg. 1994;129(2):149-156. doi:10.1001/archsurg.1994.01420260045005

Objective:  To investigate the physiologic effects of nitric oxide synthase inhibition with N-nitro-l-arginine methyl ester in an acute resuscitated model of porcine septic shock.

Design:  Randomized control trial.

Setting:  Animal research facility.

Study Subjects:  Domestic Yorkshire swine.

Interventions:  Twenty-four animals were randomly divided into one of four treatment groups as follows: normal saline resuscitation (NSR) (control group); NSR plus 200 μg/kg of lipopolysaccharide (LPS) at 1 hour after baseline (LPS group); NSR, LPS, and a continuous infusion of 50 μg/kg per minute of N-nitro-l-arginine methyl ester (NAME) at 1 hour after baseline (LPS/NAME group); and NSR and NAME (NAME group). All animals received NSR at 1 mL/kg per minute starting at baseline.

Main Outcome Measures:  Mean arterial pressure (MAP), systemic vascular resistance index (SVRI), mean pulmonary arterial pressure (MPAP), and pulmonary vascular resistance index (PVRI) were measured at baseline and hourly for 4 hours. Values at baseline and 3 hours are given below as mean (±SE).

Results:  All variables remained unchanged in the control group. The administration of LPS produced a systemic hyperdynamic response characterized by a decrease in MAP and SVRI from 66.0±3.9 to 55.0±2.8 mm Hg (P<.05) and from 422.0±22.0 to 272.0±29.0 mm (P<.05), respectively. The administration of LPS produced an increase in MPAP and PVRI from 16.3±0.8 to 30.0±1.3 mm Hg (P<.05) and from 37.0±5.3 to 119.0±13.0 mm (P<.05), respectively. In the LPS/NAME group, NAME infusion normalized MAP and increased SVRI from 506.0±40.0 to 642.0±72.0 mm (P<.05). Infusion of NAME potentiated LPS-induced pulmonary hypertension, increasing MPAP and PVRI from 16.8±0.6 to 36.0±2.8 mm Hg (P<.05) and from 59.0±3.5 to 319.0±64.0 mm (P<.05), respectively. Infusion of NAME alone increased MAP from 74.0±1.3 to 100.0±4.1 mm Hg (P<.05) and had no significant effect on MPAP and PVRI.

Conclusions:  The potentiation of LPS-induced pulmonary hypertension following NAME infusion suggests that inhibition of nitric oxide synthase may have a limited role in the treatment of septic shock.(Arch Surg. 1994;129:149-156)