Measuring extravascular lung water: animals and humans are not the same

The evolution of extravascular lung water (EVLW) monitoring is an important step forward in the hemodynamic assessment of critically ill patients

Thromboelastometry for Assessing Risks of Free Flap Thrombosis in Patients Undergoing Microvascular Surgery

Publisher Copyright: © Copyright © 2020 Vanags, Stepanovs, Ozolina, Mukans, Bjertnaes and Mamaja. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Introduction: Coagulation assessment is often missing in microvascular surgery. We aimed at evaluating the predictive value of thromboelastometry for free flap thrombosis in microvascular surgery patients. Materials and Methods: We enrolled 103 adult patients with traumatic injuries scheduled for microvascular free flap surgery into a prospective observational study. Thirty-six patients with recent trauma underwent surgery within 30 days (ES group), and were compared with 67 trauma patients who underwent surgery later than 30 days (late surgery, LS group) after the injury. Rotational thromboelastometry (RTE) was performed before surgery. Functional fibrinogen to platelet ratio (FPR) ≥ 42 was selected as the main hypercoagulability index. Free flap thrombosis was set as primary outcome. Thrombotic risk factors and duration of surgery related to free flap thrombosis were secondary outcomes. Statistical significance p 240 min, the risk of free flap thrombosis increased (OR 3.5, CI 1.16-10.6; p = 0.026) with 93.3% sensitivity and 86.7% specificity (AUC 0.85; p = 0.007). In contrast, in LS patients hypercoagulability increased the odds of free flap thrombosis (OR 8.83, CI 1.74–44.76; p = 0.009). Moreover, a positive correlation was found between FPR ≥ 42 and free flap thrombosis rate (r = 0.362; p = 0.003). In the LS group, the presence of thrombogenic comorbidities correlated with free flap thrombosis rate (OR 7, CI 1.591–30.8; p = 0.01). Conclusions: In LS patients with thrombogenic comorbidities, thromboelastometry supports the detection of hypercoagulability and predicts free flap thrombosis risk. In ES patients, postoperative hypercoagulability did not predict free flap thrombosis. Prolonged surgery time should be considered as a risk factor.Peer reviewe

Recombinant human activated protein C ameliorates oleic acid-induced lung injury in awake sheep

Introduction: Acute lung injury (ALI) may arise both after sepsis and non-septic inflammatory conditions and is often associated with the release of fatty acids, including oleic acid (OA). Infusion of OA has been used extensively to mimic ALI. Recent research has revealed that intravenously administered recombinant human activated protein C (rhAPC) is able to counteract ALI. Our aim was to find out whether rhAPC dampens OA-induced ALI in sheep. Methods: Twenty-two yearling sheep underwent instrumentation. After 2 days of recovery, animals were randomly assigned to one of three groups: (a) an OA+rhAPC group (n = 8) receiving OA 0.06 mL/kg infused over the course of 30 minutes in parallel with an intravenous infusion of rhAPC 24 mg/kg per hour over the course of 2 hours, (b) an OA group (n = 8) receiving OA as above, or (c) a sham-operated group (n = 6). After 2 hours, sheep were sacrificed. Hemodynamics was assessed by catheters in the pulmonary artery and the aorta, and extravascular lung water index (EVLWI) was determined with the single transpulmonary thermodilution technique. Gas exchange was evaluated at baseline and at cessation of the experiment. Data were analyzed by analysis of variance; a P value of less than 0.05 was regarded as statistically significant. Results: OA induced profound hypoxemia, increased right atrial and pulmonary artery pressures and EVLWI markedly, and decreased cardiac index. rhAPC counteracted the OA-induced changes in EVLWI and arterial oxygenation and reduced the OA-induced increments in right atrial and pulmonary artery pressures. Conclusions: In ovine OA-induced lung injury, rhAPC dampens the increase in pulmonary artery pressure and counteracts the development of lung edema and the derangement of arterial oxygenation

Extravascular lung water assessed by transpulmonary single thermodilution and postmortem gravimetry in sheep

INTRODUCTION: Acute lung injury is associated with accumulation of extravascular lung water (EVLW). The aim of the present study was to compare two methods for quantification of EVLW: transpulmonary single thermodilution (EVLW(ST)) and postmortem gravimetric (EVLW(G)). METHODS: Eighteen instrumented and awake sheep were randomly assigned to one of three groups. All groups received Ringer's lactate (5 ml/kg per hour intravenously). To induce lung injury of different severities, sheep received Escherichia coli lipopolysaccharide 15 ng/kg per min intravenously for 6 hours (n = 7) or oleic acid 0.06 ml/kg intravenously over 30 min (n = 7). A third group (n = 4) was subjected to sham operation. Haemodynamic variables, including EVLW(ST), were measured using a PiCCOplus monitor (Pulsion Medical Systems, Munich, Germany), and the last measurement of EVLW(ST )was compared with EVLW(G). RESULTS: At the end of experiment, values for EVLW(ST )(mean ± standard error) were 8.9 ± 0.6, 11.8 ± 1.0 and 18.2 ± 0.9 ml/kg in the sham-operated, lipopolysaccharide and oleic acid groups, respectively (P < 0.05). The corresponding values for EVLWI(G )were 6.2 ± 0.3, 7.1 ± 0.6 and 11.8 ± 0.7 ml/kg (P < 0.05). Ranges of EVLWI(ST )and EVLWI(G )values were 7.5–21.0 and 4.9–14.5 ml/kg. Regression analysis between in vivo EVLW(ST )and postmortem EVLW(G )yielded the following relation: EVLW(ST )= 1.30 × EVLW(G )+ 2.32 (n = 18, r = 0.85, P < 0.0001). The mean bias ± 2 standard deviations between EVLW(ST )and EVLW(G )was 4.9 ± 5.1 ml/kg (P < 0.001). CONCLUSION: In sheep, EVLW determined using transpulmonary single thermodilution correlates closely with gravimetric measurements over a wide range of changes. However, transpulmonary single thermodilution overestimates EVLW as compared with postmortem gravimetry

Increased Extravascular Lung Water Reduces the Efficacy of Alveolar Recruitment Maneuver in Acute Respiratory Distress Syndrome

Introduction. In acute respiratory distress syndrome (ARDS) the recruitment maneuver (RM) is used to reexpand atelectatic areas of the lungs aiming to improve arterial oxygenation. The goal of our paper was to evaluate the response to RM, as assessed by measurements of extravascular lung water index (EVLWI) in ARDS patients. Materials and Methods. Seventeen adult ARDS patients were enrolled into a prospective study. Patients received protective ventilation. The RM was performed by applying a continuous positive airway pressure of 40 cm H2O for 40 sec. The efficacy of the RM was assessed 5 min later. Patients were identified as responders if PaO2/FiO2 increased by >20% above the baseline. EVLWI was assessed by transpulmonary thermodilution before the RM, and patients were divided into groups of low EVLWI (<10 mL/kg) and high EVLWI (≥10 mL/kg). Results. EVLWI was increased in 12 patients. Following RM, PaO2/FiO2 increased by 33 (4–65) % in the patients with low EVLWI, whereas those in the high EVLWI group experienced a change by only −1((−13)–(+5)) % (P = 0.035). Conclusion. In ARDS, the response to a recruitment maneuver might be related to the severity of pulmonary edema. In patients with incresed EVLWI, the recruitment maneuver is less effective

Activation of coagulation and fibrinolysis in acute respiratory distress syndrome : a prospective pilot study

Introduction: Coagulation and fibrinolysis remain sparsely addressed with regards to acute respiratory distress syndrome (ARDS). We hypothesized that ARDS development might be associated with changes in plasma coagulation and fibrinolysis. Our aim was to investigate the relationships between ARDS diagnosis and plasma concentrations of tissue factor (TF), tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in mechanically ventilated patients at increased risk of developing ARDS. Materials and Methods: We performed an ethically approved prospective observational pilot study. Inclusion criteria: patients with PaO2/FiO2 < 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 hours, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria: age below 18 years; cardiac disease. We sampled plasma prospectively and compared patients who developed ARDS with those who did not using descriptive statistics and chi-square analysis of baseline demographical and clinical data. We also analyzed plasma concentrations of TF, t-PA and PAI-1 at inclusion (T0) and on third (T3) and seventh day (T7) of the ICU stay with nonparametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic (ROC) curve analysis. Statistical significance: p < 0.05. Results: Of 24 patients at risk, six developed mild ARDS and four of each moderate or severe ARDS, respectively, 3 ± 2 (Mean ± SD) days after inclusion. Median plasma concentrations of TF and PAI-1 were significantly higher at T7 in patients with ARDS, as compared to non-ARDS. Simultaneously, we found moderate correlations between plasma concentrations of TF and PAI-1, TF and PaO2/FiO2 and PEEP and TF. TF plasma concentration was associated with ARDS with 71% sensitivity and 100% specificity, a cut off level of 145 pg/ml and AUC 0.78, p = 0.02. PAI-1 displayed 64% sensitivity and 100% specificity with a cut off concentration of 117.5 pg/ml and AUC 0.77, p = 0.02. t-PA did not change significantly during the observation time. Conclusions: This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after seven days in ICU.publishersversionPeer reviewe

Inhaled aerosolised recombinant human activated protein C ameliorates endotoxin-induced lung injury in anaesthetised sheep

Introduction We recently demonstrated that intravenously infused recombinant human activated protein C (APC) attenuates ovine lipopolysaccharide (LPS)-induced lung injury. In this study, our aim was to find out whether treatment with inhaled aerosolised APC (inhAPC) prevents formation of increased lung densities and oedema and derangement of oxygenation during exposure to LPS. Methods: Sheep were anaesthetised during placement of intravascular introducers. After one to four days of recovery from instrumentation, the animals were re-anaesthetised, endotracheally intubated and mechanically ventilated throughout a six-hour experiment where the sheep underwent quantitative lung computed tomography. Sheep were randomly assigned to one of three groups: a sham-operated group (n = 8) receiving inhaled aerosolised saline from two hours after the start of the experiment; a LPS group (n = 8) receiving an intravenous infusion of LPS 20 ng/kg per hour and, after two hours, inhaled aerosolised saline over the next four hours; a LPS+inhAPC group (n = 8) receiving an intravenous infusion of LPS 20 ng/kg per hour and, after two hours, aerosolised APC 48 µg/kg per hour inhaled throughout the experiment. Data were analysed with analysis of variance; P less than 0.05 was regarded as significant. Results: An infusion of LPS was associated with a reduction of well-aerated lung volume and a rapid fall in arterial oxygenation that were both significantly antagonised by inhaled APC. Pulmonary vascular pressures and extravascular lung water index increased significantly during exposure to LPS, but inhaled APC had no effect on these changes. Conclusions: Inhalation of aerosolised APC attenuates LPSinduced lung injury in sheep by preventing a decline in the volume of aerated lung tissue and improving oxygenation

Associations between TNF-α, IL-6 and IL-10 Promoter Polymorphisms and Mortality in Severe Sepsis

Aims: To determine whether an association exists between TNF-α308 A/G,IL-6174G/C, and IL-10-1082 A/G promoter polymorphisms and the corresponding systemic cytokine concentrations and outcome in patients suffering from sepsis. Place and Duration of Study: The study was performed in the Intensive Care Unit (ICU) of Pauls Stradins Clinical University Hospital, Riga. Between 1 August 2006 and 31 July2008. Methodology: We enrolled 103 consecutive intensive care unit patients with sepsis into a prospective case control study. Blood samples were obtained for extraction of DNA amplifying regions of interest by means of polymerase chain reaction technique (PCR)using specific primers for TNF-α, IL-6andIL-10. Simultaneously, plasma cytokines and standard laboratory variables were determined during the first 24 h after the diagnosis. Presence of septic shock, sequential organ failure assessment score (SOFA),demographic data and clinical outcome was noticed P < 0.05 was considered as statistically significant. Results: Non-survivors had significantly higher concentrations of TNF-α, IL-6 and IL-10.The carriage of the IL-6-174C allele and IL-10-1082G allele were associated with a higher risk of mortality in patients with severe sepsis. Presence of the TNF-α-308 A allele did not influence mortality differently from those lacking this allele. Conclusion: The present study demonstrated an association of the IL-6-174 and the IL-10-1082 with increased mortality in patients suffering from severe sepsis. We found no direct association between the examined polymorphisms and the corresponding cytokine levels.publishersversionPeer reviewe

Recombinant human activated protein C attenuates endotoxin-induced lung injury in awake sheep

Introduction: Acute lung injury often complicates severe sepsis. In Gram-negative sepsis, bacterial endotoxin activates both coagulation and inflammation. Enhanced lung vascular pressures and permeability, increased extravascular lung water content and deteriorated gas exchange characterize ovine endotoxin-induced lung injury, a frequently used model of acute lung injury. Recombinant human activated protein C (rhAPC), with its anticoagulant, anti-inflammatory, fibrinolytic and antiapoptotic effects, reportedly reduces the respiratordependent days and the mortality of patients with severe sepsis. We speculate whether rhAPC antagonizes endotoxin-induced lung injury in sheep. Methods: Two groups of sheep were exposed to Escherichia coli endotoxin (lipopolysaccharide) 15 ng/kg/minute intravenously from 0 to 24 hours; one group received only lipopolysaccharide throughout (n = 8), and the other group received lipopolysaccharide in combination with rhAPC 24 μg/ kg/hour from 4 to 24 hours (n = 9). In addition, one group received rhAPC as above as the only intervention (n = 4), and four sham-operated sheep were used for determination of the α and ε isoforms of protein kinase C in pulmonary tissue. Data were assessed by one-way analysis of variance for repeated measurements. Biochemical data were analyzed using Student's t test, or using the Mann–Whitney U test when appropriate. Results: Infusion of endotoxin caused lung injury, manifested by increments in pulmonary artery pressure, in pulmonary microocclusion pressure, in pulmonary vascular downstream resistance, in pulmonary vascular permeability index, in extravascular lung water index and in deterioration of oxygenation that were all attenuated by infusion of rhAPC. Endotoxemia led to changes in inflammation and coagulation, including pulmonary neutrophil accumulation paralleled by increased TNFα and decreased protein C and fibrinogen in animal plasma, which all improved following infusion of rhAPC. Moreover, rhAPC prevented the translocation of protein kinase C α and ε isoforms from the cytosolic fraction of lung tissue extracts. Conclusion: In awake sheep, rhAPC alleviates endotoxininduced lung injury – as characterized by improvements of oxygenation, coagulation and inflammation, as well as by reversal of pulmonary hemodynamic and volumetric changes

Hypothermic cardiac arrest far away from the center providing rewarming with extracorporeal circulation

A 41-year-old man suffered hypothermic cardiac arrest after water immersion and was transported to our university hospital by ambulance helicopter for rewarming on cardiopulmonary bypass. He resumed spontaneous cardiac activity 6 h 52 min after cardiac arrest and recovered completely