Exhaled nitric oxide and carbon monoxide in mechanically ventilated brain-injured patients.

The inflammatory influence and biological markers of prolonged mechanical-ventilation in uninjured human lungs remains controversial. We investigated exhaled nitric oxide (NO) and carbon monoxide (CO) in mechanically-ventilated, brain-injured patients in the absence of lung injury or sepsis at two different levels of positive end-expiratory pressure (PEEP). Exhaled NO and CO were assessed in 27 patients, without lung injury or sepsis, who were ventilated with 8 ml kg(-1) tidal volumes under zero end-expiratory pressure (ZEEP group, n = 12) or 8 cm H2O PEEP (PEEP group, n = 15). Exhaled NO and CO was analysed on days 1, 3 and 5 of mechanical ventilation and correlated with previously reported markers of inflammation and gas exchange. Exhaled NO was higher on day 3 and 5 in both patient groups compared to day 1: (PEEP group: 5.8 (4.4-9.7) versus 11.7 (6.9-13.9) versus 10.7 (5.6-16.6) ppb (p < 0.05); ZEEP group: 5.3 (3.8-8.8) versus 9.8 (5.3-12.4) versus 9.6 (6.2-13.5) ppb NO peak levels for days 1, 3 and 5, respectively, p < 0.05). Exhaled CO remained stable on day 3 but significantly decreased by day 5 in the ZEEP group only (6.3 (4.3-9.0) versus 8.1 (5.8-12.1) ppm CO peak levels for day 5 versus 1, p < 0.05). The change scores for peak exhaled CO over day 1 and 5 showed significant correlations with arterial blood pH and plasma TNF levels (r s = 0.49, p = 0.02 and r s = -0.51 p = 0.02, respectively). Exhaled NO correlated with blood pH in the ZEEP group and with plasma levels of IL-6 in the PEEP group. We observed differential changes in exhaled NO and CO in mechanically-ventilated patients even in the absence of manifest lung injury or sepsis. These may suggest subtle pulmonary inflammation and support application of real time breath analysis for molecular monitoring in critically ill patients.

Serum of patients with septic shock stimulates the expression of Trem-1 on U937 monocytes.

OBJECTIVES: To describe the concentrations of sTREM-1 in patients with sepsis and to explore the effects of their serum on the expression of TREM-1 on U937 monocytes. METHODS: Blood was sampled at regular time intervals in 56 patients with sepsis. Concentrations of tumour necrosis factor-alpha (TNFalpha), interleukin-1beta (IL-1alpha), IL-6, IL-8, IL-10 and IL-12p70 and sTREM-1 were measured. U937 monocytes were incubated in the presence of serum at sepsis onset. RESULTS: Median sTREM-1 concentration on day 1 for patients with septic shock was 915 pg/ml and 228.5 pg/ml for those without shock (p = 0.002). TNFalpha, IL-1alpha, IL-6, IL-8 and IL-10 did not differ between them. A positive correlation was found between changes of sTREM-1 and SOFA scores from day 1 to 7. Sera of patients with septic shock evoked a significant increase of the expression of TREM-1. The concentrations of TNFalpha and IL-8 in supernatants increased only after stimulating with sera of patients without shock, but not after stimulating with sera of patients with shock. CONCLUSIONS: Levels of sTREM-1 correlated with sepsis severity. sTREM-1 is considerably higher in patients with shock compared to patients without shock. The serum of shocked patients could stimulate the expression of TREM-1 on U937 monocytes.

Stimulation of monocytes is a pathway involved in systemic inflammatory response following haemorrhagic shock resuscitation: the effect of hypoxaemic resuscitation.

The present study was designed to investigate whether serum of animals subjected to hypoxaemic resuscitation from haemorrhagic shock may be a weak stimulant for monocytes or not. Twenty rabbits were subjected to haemorrhagic shock after blood exsanguination; resuscitation was performed by infusion of the shed blood in eight rabbits under normoxaemic conditions (NormoxRes) and in 12 under hypoxaemic conditions (HypoxRes); seven rabbits were subjected to sham operation. Malondialdehyde (MDA) and tumour necrosis factor (TNF)-alpha were estimated in serum at serial time intervals; the serum was applied for stimulation of U937 monocytes with or without the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Expression of triggering receptor expressed on myeloid cells-1 (TREM-1) on U937 was also assessed by flow cytometric analysis. Death supervened in four animals of the NormoxRes (50%) and in one animal of the HypoxRes group (8.33%, P: 0.032). Serum levels of TNF-alpha and MDA were higher in NormoxRes compared to HypoxRes animals. Expression of TREM-1 on U937 monocytes was similar after stimulation with serum sampled from both groups. Concentrations of interleukin (IL)-1beta, IL-6 and IL-8 of monocyte supernatants were higher after stimulation with serum of NormoxRes than HypoxRes rabbits. Production of cytokines after stimulation with serum was decreased significantly after addition of SB203580. It is concluded that stimulation of monocytes may contribute to the generation of the systemic inflammatory response during reperfusion after ischaemia. Lower stimulation of the p38 MAPK-mediated production of IL-1beta, IL-6 and IL-8 by monocytes may be implicated as an explanation for the benefits shown for the host when resuscitation is performed under hypoxaemic conditions.