Nitrite/nitrate (NOx) levels and hemodynamics during septic shock (original) (raw)
Related papers
Brazilian Journal of …, 1999
To investigate the role of nitric oxide in human sepsis, ten patients with severe septic shock requiring vasoactive drug therapy and mechanical ventilation were enrolled in a prospective, open, non-randomized clinical trial to study the acute effects of methylene blue, an inhibitor of guanylate cyclase. Hemodynamic and metabolic variables were measured before and 20, 40, 60, and 120 min after the start of a 1-h intravenous infusion of 4 mg/kg of methylene blue. Methylene blue administration caused a progressive increase in mean arterial pressure (60 [55-70] to 70 [65-100] mmHg, median [25-75th percentiles]; P<0.05), systemic vascular resistance index (649 [479-1084] to 1066 [585-1356] dyne s-1 cm-5 m-2 ; P<0.05) and the left ventricular stroke work index (35 [27-47] to 38 [32-56] g m-1 m-2 ; P<0.05) from baseline to 60 min. The pulmonary vascular resistance index increased from 150 [83-207] to 186 [121-367] dyne s-1 cm-5 m-2 after 20 min (P<0.05). Mixed venous saturation decreased from 65 [56-76] to 63 [55-69]% (P<0.05) after 60 min. The PaO 2 /FiO 2 ratio decreased from 168 [131-215] to 132 [109-156] mmHg (P<0.05) after 40 min. Arterial lactate concentration decreased from 5.1 ± 2.9 to 4.5 ± 2.1 mmol/ l, mean ± SD (P<0.05) after 60 min. Heart rate, cardiac filling pressures, cardiac output, oxygen delivery and consumption did not change. Methylene blue administration was safe and no adverse effect was observed. In severe human septic shock, a short infusion of methylene blue increases systemic vascular resistance and may improve myocardial function. Although there was a reduction in blood lactate concentration, this was not explained by an improvement in tissue oxygenation, since overall oxygen availability did not change. However, there was a significant increase in pulmonary vascular tone and a deterioration in gas exchange. Further studies are needed to demonstrate if nitric oxide blockade with methylene blue can be safe for patients with septic shock and, particularly, if it has an effect on pulmonary function.
Role of active nitrogen molecules in progression of septic shock
Acta Anaesthesiologica Scandinavica, 2011
Introduction: Active nitrogen molecules are formed as a result of cell metabolism. They are essential for cell metabolism, but when produced in excess, they contribute to the pathogenesis of several disease processes. These nitrogen molecules play an important role in vascular instability of septic shock. This study was planned to detect the role of active nitrogen molecules in the progression of septic shock. Materials and methods: Blood samples were collected from 118 critically ill patients admitted in ICU and from 95 healthy relatives accompanying the patients. Patients were categorized into three groups: systemic inflammatory response syndrome (n = 54), sepsis (n = 35) and septic shock (n = 29). Plasma total nitrite (nitrites and nitrates), cytokines like tumour necrosis factor-a (TNF-a) and plasma lactate were measured to assess inflammatory activity and severity of septic shock. Results: High plasma levels of nitrite and nitrate (No2-/No3-) were observed in critically ill patients (mean level 78.92 mmol/l in sepsis and 97.20 mmol/l in septic shock). Mean plasma TNF-a level in sepsis was 213.50 pg/ml and septic shock was 227.38 pg/ml. Conclusion: Plasma No2-/No3-and TNF-a levels were high in patients with sepsis and septic shock, which increased with severity of sepsis.
Hemodynamic and Cardiovascular Effects of Nitric Oxide Modulation in the Therapy of Septic Shock
Pharmacotherapy, 2000
Nitric oxide synthase (NOS) of the inducible subtype (iNOS) plays a pivotal role in vasodilation associated with sepsis. Various biochemical pathways are involved, revealing targets for inhibiting the consequence of iNOS activation. Interactions of transcription factors, inducers, cofactors, and regulators of iNOS are important in understanding the development of iNOS inhibitors. Inhibition through L-arginine analogs, depletion of arginine, inhibition of cofactors, modulating gene transcription, and scavenging nitric oxide have been studied. Human studies were conducted only with nonselective L-arginine analogs. Reduction of mortality from sepsis was not reported. It is anticipated that iNOS-specific compounds will be clinically useful. The focus of future human trials will be on these agents. Although ideal therapy for treating vasodilation from sepsis is not available, research into the pathophysiology of NOS in sepsis clarified the complexities surrounding this therapeutic dilemma. NOS = nitric oxide synthase; nNOS = neuronal NOS; iNOS = inducible NOS; eNOS = endothelial NOS; NMDA = N-methyl-D-aspartate; ADP = adenosine diphosphate.
Nitric Oxide and Vascular Reactivity in Sepsis
Shock, 2008
Sepsis and septic shock are major causes of morbidity and mortality in critically ill patients. Sepsis and septic shock induce a profound fall in the peripheral vascular tone. NO has been implicated as a key player in vascular changes of sepsis and septic shock. In this brief review, two points are focused in greater detail: first, the involvement of guanylate cyclase and potassium channels in NO vascular effects in sepsis; second, the role played by NO and its two effectors in the long-lasting modifications of vascular reactivity in sepsis. Some recent developments in the area are reviewed.
Nitrogen oxide levels in patients after trauma and during sepsis
1991
The mediators responsible for maintenance of the hyperdynamic state and the low systemic vascular resistance (SVR) observed in sepsis have not been elucidated. Nitric oxide ( N = 0) is a mediator with numerous functions, including regulation of vascular tone and a role in macrophage-mediated cytostasis and microbiostasis. Thirty-nine critically ill trauma and septic patients were studied to determine the relationship between -N = 0 production and the hyperdynamic state. High plasma levels of N02-/NO3-(the stable end products of * N = 0) were observed in septic patients (p < 0.02). Low SVR and high endotoxin levels were associated with high N02-/NO3values (p = 0.029, p = 0.002). Changes in * N = 0 levels may mediate the vasodilation seen in sepsis. Low N02-/NO3levels were observed in trauma patients (p < 0.001) and remained low even in the presence of sepsis (p = 0.001).
Compartmentalised inducible nitric-oxide synthase activity in septic shock
Lancet, 2000
Previous experimental studies support a role for inducible nitric-oxide synthase (iNOS) in the pathogenesis of severe sepsis. The aim of the study was to characterise iNOS activity in different tissues in patients with septic shock.13 consecutive patients with septic shock caused by cellulitis were enrolled. Skin, muscle, fat, and artery samples were obtained from normal, inflamed, and putrescent areas to measure iNOS activity, and concentrations of tumour necrosis factor α (TNFα) and interleukin 1β (IL-1β). In two patients, iNOS activity was also assessed in peripheral blood mononuclear cells (PBMC) incubated with microorganisms causing the sepsis, or in macrophages isolated from suppurating peritoneal fluid incubated with IL-1β.Compared with normal and inflamed areas, iNOS activity was increased in putrescent areas for muscle (71-fold [95% CI 20–259] vs normal areas, 69-fold [19–246] vs inflammed areas; p<0·01 for each) and for fat (68-fold [23–199] and 49-fold [18–137], respectively; p<0·01), but not for skin. Compared with normal areas, putrescent areas of arteries showed increased iNOS expression (1280-fold [598–3153]; p<0·01). Compared with normal areas, TNFα and IL-1β were increased in putrescent areas of arteries (223-fold and 41-fold, respectively; p<0·01 for each). PBMCs and tissue macrophages expressed iNOS. Plasma nitrite/nitrate concentrations inversely correlated with mean arterial pressure and systemic vascular resistance.In human septic shock we found that iNOS activity is compartmentalised at the very site of infection and parallels expression of TNFα and IL-1β. PBMCs and tissue macrophages can be a cellular source for iNOS.
British Journal of Anaesthesia, 2005
Background. The vasodilatation characteristic of human septic shock is conventionally attributed to increased nitric oxide production, primarily by extrapolation of animal and human in vitro studies. There are no conclusive studies of human disease, and the cellular source of nitric oxide in human sepsis is not known. Haem oxygenase is upregulated by oxidative stress, but little is known about haem oxygenase expression in human sepsis. Haem oxygenase may modulate nitric oxide production, and may also have a direct effect on vascular tone. Methods. Mesenteric arterial smooth muscle (ASM) (obtained during laparotomy) and peripheral blood mononuclear cells (PBMCs) were obtained from patients with early septic shock and from control patients. mRNA levels were determined by real-time RT-PCR. Results. mRNA for inducible and endothelial nitric oxide synthase was reduced in both ASM and PBMCs from septic patients. In contrast, inducible haem oxygenase mRNA was increased in sepsis in both cell types. Conclusions. These results suggest that, rather than being induced, the enzymes which produce nitric oxide are reduced at this time point in human septic shock. Thus many of the in vitro models of sepsis studied to date may not fully replicate human disease. The increase in haem oxygenase expression confirms that these cells have been subjected to oxidative stress in sepsis. The activity of induced haem oxygenase may limit nitric oxide production, while possibly causing vasodilation through production of carbon monoxide.
Regulatory Peptides, 1996
This study is aimed to inve, stigate the relationship between plasma concentrations of nitrite and nitrate as a measure of ongoing nitric oxide (NO) production, the vasodilatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), endotoxemia and hemodynamic changes in huraan septic shock. Thirteen patients with septic shock were studied within 6 h after the development of hypotension. Hemodynamic measurements and blood samples were recorded simultaneously at 2-h intervals from study admission. Eighteen normotensive patients with sepsis were included as control group of patients. On study entry, circulating levels of endotoxin did not relate to either CGRP or n!itrite and nitrate plasma values. Septic shock patients had significantly higher plasma CGRP, and nitrite and nitrate concentrations, at each of the four time points, than patients with sepsis, as well as both groups of patients compared to normal subjects. No differences were found in plasma SP levels between the two groups of patients. For pooled data from all septic shock patients and measurements (n = 52), both plasma concentrations of CGRP and nitrite and nitrate were inversely correlated, independently from each other, to systemic vascular resistance. On study admission and at 2-h intervals, plasma CGRP concentrations correlated directly with nitrite and nitrate values. Our observations, thus, point to CGRP acting in concert with NO as important mediators responsible for hypotension in human septic shock.
Oxidative Medicine and Cellular Longevity
Background. Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls. Methods and Results. Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls ( n = 10 , age 67.8 ± 3.2 , male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% ...