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Objective: To evaluate (1) levels of the host-defense/antimicrobial peptide LL-37 in patients with trauma and hemorrhagic shock (HS) and (2) the effects of a synthetic host-defense peptide; Pep19-4LF on multiple organ failure (MOF) associated with HS. Background: HS is a common cause of death in severely injured patients. There is no specific therapy that reduces HS-associated MOF. Methods: (1) LL-37 was measured in 47 trauma/HS patients admitted to an urban major trauma center. (2) Male Wistar rats were submitted to HS (90 min, target mean arterial pressure: 27--32mm Hg) or sham operation. Rats were treated with Pep19-4LF [66 (n = 8) or 333µg/kg ⋅ h (n = 8)] or vehicle (n = 12) for 4 hours following resuscitation. Results: Plasma LL-37 was 12-fold higher in patients with trauma/HS compared to healthy volunteers. HS rats treated with Pep19-4LF (high dose) had a higher mean arterial pressure at the end of the 4-hour resuscitation period (79±4 vs 54±5mm Hg) and less renal dysfunction, liver injury, and lung inflammation than HS rats treated with vehicle. Pep19-4LF enhanced (kidney/liver) the phosphorylation of (1) protein kinase B and (2) endothelial nitric oxide synthase. Pep19-4LF attenuated the HS-induced (1) translocation of p65 from cytosol to nucleus, (2) phosphorylation of IkB kinase on Ser176/180, and (3) phosphorylation of IkBa on Ser32/36 resulting in inhibition of nuclear factor kappa B and formation of proinflammatory cytokines. Pep19-4LF prevented the release of tumor necrosis factor alpha caused by heparan sulfate in human mononuclear cells by binding to this damage-associated molecular pattern. Conclusions: Trauma-associated HS results in release of LL-37. The synthetic host-defense/antimicrobial peptide Pep19-4LF attenuates the organ injury/dysfunction associated with HS. [ABSTRACT FROM AUTHOR]

Background: Patients and medical staff are exposed to high noise levels in ICUs, which may have a negative impact on their health. Due to the diversity of noise sources present, including the operating noise of medical devices, staff conversations and the unwrapping of disposables, noise profiles are varied. Psychoacoustics deals with the analysis of sound, focusing on its effects on physiological perception and stress.Objectives: The aim of our study was to examine and to classify noise and its psychoacoustic properties in different locations in our ICU at different times. The impact of noise on subjective parameters and stress-related physiological data was also assessed with and without interventional methods.Design: A randomised, controlled, single-blinded clinical trial.Setting: University Hospital, from November 2010 to May 2011.Patients: One hundred and forty-four patients in the ICU.Interventions: In the first part, multidisciplinary psychoacoustic measurement was performed on the patients in our ICU. In the subsequent clinical trial, patients were equipped with effective earplugs, less effective earplugs and no earplugs. Thereafter, active noise cancellation headphones with or without sound masking were employed on a third patient population.Main Outcome Measures: Cortisol and α-amylase in saliva, skin conductance measures, vital signs, psychoacoustic analyses and two standardised questionnaires [State-Trait Anxiety Inventory (STAI) and Hospital Anxiety and Depression Scale (HADS)] were assessed.Results: In the first part, the mean ± standard deviation (SD) subjective loudness was 9.2 ± 4.0 sone. Although absolute sound pressure level and loudness were lower during the night, the number of loud events increased significantly. Skin conductance in the earplug groups was significantly reduced in comparison to that in the control population but not the active noise reduction groups. Nevertheless, noise reduction was found to be comfortable for most patients.Conclusion: Noise in the ICU is of high clinical relevance. Diverse noise reduction methods, such as earplugs and active noise cancellation, are available. The avoidance of unnecessary noise, however, should be the primary focus.Trial Registration: German Clinical Trials Register (DRKS00000534). [ABSTRACT FROM AUTHOR]

Different minimally invasive haemodynamic monitoring techniques are commercially available today and in the recent years they have proved adequate in replacing the pulmonary artery catheter under certain clinical conditions.Moreover, several of these techniques provide additional new parameters primarily related to preload assessment.Therefore, in order to be used in daily clinical practice, the diversity of minimally invasive haemodynamic monitoring requires knowledge of the different techniques, the different parameters provided by the devices and their clinical validity. The aim of the present article is to review the most widely used minimally invasive cardiac output monitoring techniques; emphasize the new parameters available for preload assessment;and propose a modular stepwise monitoring concept. [ABSTRACT FROM AUTHOR]

Adrenomedullin is a vasoactive peptide that improves endothelial barrier function in sepsis, but may also cause hypotension and organ failure. Treatment with a non-neutralizing monoclonal anti-adrenomedullin antibody showed improvement in murine sepsis models. We tested the effects of the humanized monoclonal anti-adrenomedullin antibody Adrecizumab in a porcine two-hit model of hemorrhagic and septic shock.In this randomized, blinded study 12 German Landrace pigs were bled to half of baseline mean arterial pressure for 45 min. Sepsis was induced using an Escherichia coli clot placed into the abdominal cavity 6 h after hemorrhagic shock. Animals received either 2 mg/kg BW anti-adrenomedullin antibody or vehicle solution immediately after sepsis induction. After 4 h, resuscitation was initiated using balanced crystalloids and noradrenalin to maintain a central venous pressure of 8 to 12 mm Hg, a mean arterial pressure ≥ 65 mm Hg, and a ScvO2 ≥70% for another 8 h. Hemodynamic parameters, laboratory parameters, and kidney histology were assessed.The amount of volume resuscitation was significantly lower and significantly less animals developed a septic shock in the antibody-treated group, compared with the vehicle group. Kidney histology showed significantly lower granulocytes in both cortex and medulla in antibody-treated animals, while the remaining four kidney measures (serum creatinine and urine output and cortical and medullary injury in histopathology) did not reach the significance levels. After induction of sepsis, plasma adrenomedullin increased immediately in both the groups, but increased quicker and more pronounced in the antibody group.In this two-hit shock model, treatment with an anti-adrenomedullin antibody significantly increased plasma adrenomedullin levels, while significantly less animals developed septic shock and renal granulocyte extravasation was significantly reduced. Thus, therapy with Adrecizumab may provide benefit in sepsis, and clinical investigation of this drug candidate is warranted.

Purpose of Review: Evidence-based fluid therapy is complicated by blurred boundaries toward other fields of therapy and the majority of trials not focusing on patient-relevant outcomes. Additionally, recent trials unsettled the faith in traditional concepts on fluid therapy. The article reviews the evidence on diagnosis and treatment of hypovolemia and discusses the use of balanced solutions and early goal-directed therapy (EGDT) in septic shock resuscitation., Recent Findings: Hypovolemia should be diagnosed and its treatment guided by a multifaceted approach, including medical history, physical examination, volume responsiveness, and technical parameters - dynamic indicators, volumetric indicators, sonography, and metabolic indicators. Central venous pressure and pulmonary artery occlusion pressure should be avoided. In ICU patients, balanced crystalloids should primarily be used, because unbalanced infusions (especially saline) cause hyperchloremic acidosis which is associated with renal impairment and infections. Colloids are beneficial to restore blood volume rapidly. Hydroxyethyl starch may be harmful although the validity of the respective recent studies is limited by methodological flaws. Early aggressive fluid therapy is still beneficial in septic shock resuscitation, despite recent trials challenging the EGDT concept. Today, 10 years after Rivers, 'usual care' includes aggressive fluid resuscitation that is as effective as formal EGDT., Summary: Evidence-based fluid therapy includes a multifaceted diagnostic approach, the primary use of balanced crystalloids and early aggressive (septic) shock resuscitation.

Objectives: Capillary leakage, a frequent complication in septic shock, is characterized by loss of intravasal fluid resulting in generalized edema and hemodynamic instability despite massive fluid therapy. We have shown that administration of an established colloid 200/0.5 hydroxyethyl starch (HES) stabilized plasma volume in a porcine septic shock model. Recently, a new HES with a low molecular weight (130 kD) and lower molar substitution (0.42) has been developed. In this study, we compared effects of HES 130/0.42 and HES 200/0.5 on capillary leakage in porcine septic shock., Design: Prospective randomized, controlled animal study., Setting: University department of anesthesiology., Subjects: Fourteen pigs (22.9 +/- 2.8 kg)., Interventions: Anesthetized and mechanically ventilated pigs were observed over 6 hrs., Measurement and Main Results: Septic shock was induced with fecal peritonitis (0.75 g.kg of body weight autologous feces). Animals were allocated to volume-replacement therapy with either HES 130/0.42 (n = 5) or HES 200/0.5 (n = 5) and compared with nonseptic controls receiving HES 130/0.42 (n = 4). Infusion rate was titrated to maintain a central venous pressure of 12 mm Hg. Albumin escape rate was calculated using iodine 125-labeled albumin. Plasma volume was determined using chromium-51-tagged erythrocytes. Albumin escape rate increased significantly in both groups in comparison to controls (HES 200/0.5, 45% +/- 3; HES 130/0.42, 38% +/- 5), but this increase was significantly smaller with HES 130/0.42. Both HES 200/0.5 (-14%, not significant) and HES 130/0.42 (-1%, not significant) stabilized plasma volume compared with controls. Systemic oxygenation was not significantly altered in either group., Conclusions: In this porcine septic shock model, HES 130/0.42 attenuated capillary leakage significantly more effectively than HES 200/0.5.

Purpose of Review: Mixed venous and central venous oxygen saturations reflect the balance between oxygen requirement and oxygen delivery, and thus may be used to assess the adequacy of tissue oxygenation. This review discusses recent data on the impact of using venous oximetry by obtaining mixed venous oxygen saturation or central venous oxygen saturation as useful monitoring parameters in critically ill patients., Recent Findings: Monitoring of changes in the central venous oxygen saturation after major surgery has been shown to be associated with outcome. Furthermore, early goal-directed therapy for patients with severe sepsis or septic shock, which includes treatment goals for mean arterial pressure, central venous pressure, and central venous oxygen saturation, was able to increase survival in these patients. In contrast, pulmonary artery catheter usage does not affect outcome in critically ill patients., Summary: Early goal-directed therapy should be implemented in the initial resuscitation of septic patients. Central venous saturation may have prognostic significance following major surgery. Further evaluation of peri-operative trends in central venous saturation is required. Measurement of central venous oxygen saturation can easily be applied in intensive care unit patients and offers a useful, indirect indicator for the adequacy of tissue oxygenation.

Objectives: To compare the accuracy of an integrated fiberoptic monitoring system using transpulmonary thermo-dye dilution technique to measure blood volume (BV) with standard method using chromium-51-tagged erythrocytes in septic shock., Design: Prospective blinded animal laboratory study., Setting: University department of anesthesiology., Subjects: Thirty-five anesthetized and mechanically ventilated pigs (21.4 +/- 2.2 kg) were investigated over a period of 6 hrs., Interventions: Septic shock was induced with fecal peritonitis (0.75 g . kg per body weight autologous feces). A central venous catheter was used for injection of the indicator dyes., Measurements and Main Results: BV was measured by detecting indocyanine green using a 4-Fr aortic catheter with an integrated fiberoptic and thermistor connected to a computer system for calculation of transpulmonary indicator dilution BV (BVTPID). Cr-tagged erythrocytes were used as standard method of BV measurement (BV-Cr). Hemodynamic treatment scheme was aimed at maintenance of a central venous pressure of 12 mm Hg. Data were analyzed using Bland-Altman analyses. One hundred and five data pairs of simultaneous BV measurements were yielded during hemodynamic stability with a mean BVTPID of 64.2 +/- 17.8 mL . kg. Mean BV-Cr was 83.1 +/- 17.0 mL . kg. Linear regression equation was BVTPID = 0.58 x BV-Cr + 15.8 (r = .56, p < .01). Mean bias was 18.9 mL . kg (95% confidence interval, 15.7-22.1 mL . kg), with limits of agreement of -13.9 to 51.7 mL . kg., Conclusions: Transpulmonary indicator dilution for blood volume measurement agrees moderately with standard method using Cr-tagged erythrocytes in porcine septic shock.