Soluble urokinase plasminogen activator receptor informs on the progression course after multiple injuries.

PURPOSE: The purpose of this study is to study the use of soluble urokinase plasminogen activator receptor (suPAR) for the prognosis of multiple organ dysfunction (MOF) after multiple traumas. METHODS: Serum suPAR was measured within the first 24 h after multiple injuries in 85 patients. Measurements were repeated after 4 d or at sepsis onset. RESULTS: Odds ratio for trauma-associated MOF was 4.09 (p: 0.026) with admission suPAR greater than 8 ng/ml. More than 40% increases of suPAR were associated with odds ratio 9.33 (p: 0.047) for severe sepsis. CONCLUSIONS: suPAR is a useful surrogate biomarker for development of MOF and severe sepsis after multiple traumas.

Defective cytokine production early after multiple traumas: Modulation in severe sepsis.

The exact time frame of multiple trauma-induced immunosuppression and the immune mechanisms mediating transition to severe sepsis are largely unknown. Peripheral blood mononuclear cells were isolated from 69 patients with multiple injuries within the first 24h from injury and from 36 healthy volunteers and stimulated for cytokine production. Circulating endotoxins were measured by the kinetic LAL assay. Measurements were repeated the first 24h of sepsis onset. Patients had defective responses for tumour necrosis factor-alpha (TNFα), interleukin (IL)-10, IL-17 and interferon-gamma (IFNγ) using a broad-panel of bacterial stimuli. Production of IFNγ was pronounced for patients with trauma-related multiple organ failure (MOF). Thirty-six patients developed severe sepsis. At that time, production of TNFα was increased compared to baseline. The increase was greater among non-survivors than among survivors. Enhanced TNFα production on sepsis onset was a main finding of patients without endotoxemia. Immunosuppression of both innate and adaptive cytokine responses appears as early as the first 24h from injury. Transition into severe sepsis due to bacterial superinfection is accompanied by enhanced production of TNFα and this is linked with unfavorable outcome.

Early administration of hydrocortisone replacement after the advent of septic shock: impact on survival and immune response*.

OBJECTIVES: To investigate the impact of early initiation of hydrocortisone therapy on the clinical course of septic shock and on cytokine release. DESIGN: Prospective study in patients with septic shock treated with low doses of hydrocortisone. SETTING: ICUs and general wards. PATIENTS: Over a 2-year period, 170 patients with septic shock treated with low doses of hydrocortisone were enrolled. Blood was sampled from 34 patients for isolation of peripheral blood mononuclear cells and cytokine stimulation before and 24 hours after the start of hydrocortisone. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After quartile analysis, patients were divided into those with early initiation of hydrocortisone (< 9 hr after vasopressors, n = 46) and those with late initiation of hydrocortisone (> 9 hr after vasopressors, n = 124). After adjusting for disease severity and type of infection, a protective effect of early hydrocortisone administration against unfavorable outcome was found (hazard ratio, 0.20; p = 0.012). Time of discontinuation of vasopressors was earlier among patients with initiation of hydrocortisone within 9 hours. Production of tumor necrosis factor-α was lower among patients who had had hydrocortisone early. CONCLUSIONS: In patients receiving hydrocortisone for septic shock, early initiation of treatment was associated with improved survival. This treatment was also associated with attenuated stimulation of tumor necrosis factor-α.

Non-interventional monitoring of expiratory flow limitation during experimental mechanical ventilation.

BACKGROUND: Expiratory flow limitation (EFL) is common among patients in the intensive care unit under mechanical ventilation (MV) and may have significant clinical consequences. In the present study, we examine the possibility of non-interventional detection of EFL during experimental MV. METHODS: Eight artificially ventilated New Zealand rabbits were included in the experiments. EFL was induced during MV by application of negative expiratory pressure (-5, -8 and -10 hPa) and detected by the negative expiratory pressure technique. Airway pressure (P aw) and gas flow (V') were digitally recorded and processed off-line for the evaluation of respiratory mechanics. The method is based on the computation and monitoring of instantaneous respiratory resistance R rs(t). The resistive pressure (P aw,res(t)) is calculated by subtracting from P aw its elastic component and the end-expiratory pressure, as assessed by linear regression. Then, R rs(t) is computed as the instant ratio P aw,res(t)/V'(t). RESULTS: Two completely different patterns of expiratory R rs(t) separate the cases with EFL from those without EFL. Small and random fluctuations are noticed when EFL is absent, whereas the onset of EFL is accompanied by an abrupt and continuous rise in R rs(t), towards the end of expiration. Thus, EFL is not only detected but may also be quantified from the volume still to be expired at the time EFL occurs. CONCLUSION: The proposed technique is a simple, accurate and non-interventional tool for EFL monitoring during MV.

Survival after multiple traumas is associated with improved outcomes from gram-negative sepsis: Clinical and experimental evidence.

OBJECTIVES: We investigated the susceptibility to Gram-negative sepsis after multiple traumas (MT). METHODS: From a prospective cohort of 5076 Greek patients with sepsis, 16 with Gram-negative bacteremia after MT were compared with 204 patients well-matched for severity, comorbidities and appropriateness of antimicrobials; circulating mononuclear cells were isolated and stimulated for the release of interleukin (IL)-10. Male C57Bl6J mice were subject to MT (right pneumothorax and right femur fracture) followed after 72 h by the intravenous challenge with Pseudomonas aeruginosa. Survival was recorded and splenocytes were isolated for cytokine stimulation. RESULTS: 28-day mortality after MT was 18.8% compared to 48.0% of comparators (48.0%) (odds ratio 0.25, p: 0.035). This was confirmed after logistic regression analysis taking into consideration comorbidities and age. Stimulation of IL-10 was enhanced from MT patients. Survival of mice challenged by P. aeruginosa 72 h after MT was prolonged compared to mice challenged by P. aeruginosa without prior MT. Cytokine production was decreased 24 h after MT and restored 96 h thereafter. Production of IL-10 was particularly pronounced from splenocytes of mice challenged by P. aeruginosa after MT. CONCLUSIONS: Survival after MT is accompanied by favorable immune responses allowing survival benefit from Gram-negative sepsis. This is associated with increased IL-10 release.

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis.

PURPOSE: The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. METHODS: A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. RESULTS: Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). CONCLUSIONS: Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.