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Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine With Morbidity and Mortality in Patients With Necrotizing Soft Tissue Infections.

ABSTRACT: BACKGROUND:The nitric oxide system could play an important role in the pathophysiology related to necrotizing soft tissue infection (NSTI). Accordingly, we investigated the association between plasma nitrite level at admission and the presence of septic shock in patients with NSTI. We also evaluated the association between nitrite, asymmetric dimethylarginine (ADMA), L-arginine, L-arginine/ADMA ratio, and outcome. METHODS:We analyzed plasma from 141 NSTI patients taken upon hospital admission. The severity of NSTI was assessed by the presence of septic shock, Simplified Acute Physiology Score (SAPS) II, Sepsis-Related Organ Failure Assessment (SOFA) score, use of renal replacement therapy (RRT), amputation, and 28-day mortality. RESULTS:No difference in nitrite levels was found between patients with and without septic shock (median 0.82??mol/L [interquartile range (IQR) 0.41-1.21] vs. 0.87??mol/L (0.62-1.24), P?=?0.25). ADMA level was higher in patients in need of RRT (0.64??mol/L (IQR 0.47-0.90) vs. (0.52??mol/L (0.34-0.70), P?=?0.028), and ADMA levels correlated positively with SAPS II (rho?=?0.32, P?=?0.0002) and SOFA scores (rho?=?0.22, P?=?0.01). In a logistic regression analysis, an L-arginine/ADMA ratio below 101.59 was independently associated with 28-day mortality, odds ratio 6.03 (95% confidence interval, 1.41-25.84), P?=?0.016. None of the other analyses indicated differences in the NO system based on differences in disease severity. CONCLUSIONS:In patients with NSTI, we found no difference in baseline nitrite levels according to septic shock. High baseline ADMA level was associated with the use of RRT and patients with a low baseline L-arginine/ADMA ratio were at higher risk of dying within 28 days after hospital admission.

SUBMITTER: Hansen MB

PROVIDER: S-EPMC5929495 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine With Morbidity and Mortality in Patients With Necrotizing Soft Tissue Infections.

Hansen Marco B MB Rasmussen Lars S LS Garred Peter P Pilely Katrine K Wahl Anna M AM Perner Anders A Madsen Martin B MB Hedegaard Elise R ER Simonsen Ulf U Hyldegaard Ole O

Shock (Augusta, Ga.) 20180601 6

<h4>Background</h4>The nitric oxide system could play an important role in the pathophysiology related to necrotizing soft tissue infection (NSTI). Accordingly, we investigated the association between plasma nitrite level at admission and the presence of septic shock in patients with NSTI. We also evaluated the association between nitrite, asymmetric dimethylarginine (ADMA), L-arginine, L-arginine/ADMA ratio, and outcome.<h4>Methods</h4>We analyzed plasma from 141 NSTI patients taken upon hospit ...[more]

PMID: 28863028

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Project description:Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients.Post hoc analysis of the Hemodialysis (HEMO) Study.1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization.ADMA and SDMA measured in stored specimens.Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbid conditions, albumin level, and residual kidney function).Mean age of patients was 57±14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9±0.2?mol/L) and SDMA levels (4.3±1.4?mol/L) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29-2.58), sudden cardiac death (1.79; 1.19-2.69), first cardiovascular event (1.50; 1.20-1.87), and any-cause death (1.44; 1.13-1.83). Compared to the lowest ADMA quintile (<0.745 ?mol/L), the highest ADMA quintile (?1.07?mol/L) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44-3.05), sudden cardiac death (2.06; 1.46-2.90), first cardiovascular event (1.75; 1.35-2.27), and any-cause death (1.56; 1.21-2.00). SDMA level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68).Single time-point measurement of ADMA and SDMA.ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.

Dataset Information

Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine With Morbidity and Mortality in Patients With Necrotizing Soft Tissue Infections.

Publications

Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine With Morbidity and Mortality in Patients With Necrotizing Soft Tissue Infections.

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