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

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

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

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

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

Comparison of Goal-Directed Hemodynamic Optimization Using Pulmonary Artery Catheter and Transpulmonary Thermodilution in Combined Valve Repair: A Randomized Clinical Trial

Our aim was to compare the effects of goal-directed therapy guided either by pulmonary artery catheter (PAC) or by transpulmonary thermodilution (TTD) combined with monitoring of oxygen transport on perioperative hemodynamics and outcome after complex elective valve surgery. Measurements and Main Results. Forty patients were randomized into two equal groups: a PAC group and a TTD group. In the PAC group, therapy was guided by mean arterial pressure (MAP), cardiac index (CI) and pulmonary artery occlusion pressure (PAOP), whereas in the TTD group we additionally used global end-diastolic volume index (GEDVI), extravascular lung water index (EVLWI), and oxygen delivery index (DO2I). We observed a gradual increase in GEDVI, whereas EVLWI and PAOP decreased by 20–30% postoperatively (P < 0.05). The TTD group received 20% more fluid accompanied by increased stroke volume index and DO2I by 15–20% compared to the PAC group (P < 0.05). Duration of mechanical ventilation was increased by 5.2 hrs in the PAC group (P = 0.04). Conclusions. As compared to the PAC-guided algorithm, goal-directed therapy based on transpulmonary thermodilution and oxygen transport increases the volume of fluid therapy, improves hemodynamics and DO2I, and reduces the duration of respiratory support after complex valve surgery

Влияние мультизональной деконтаминации верхних дыхательных путей на частоту вентилятор-ассоциированной пневмонии: многоцентровое рандомизированное пилотное исследование

АКТУАЛЬНОСТЬ: Вентилятор-ассоциированная пневмония (ВАП) остается ведущей нозокомиальной инфекцией в отделении интенсивной терапии. ВАП увеличивает продолжительность госпитализации и длительность искусственной вентиляции легких (ИВЛ), что ассоциируется с атрибутивной летальностью. ЦЕЛЬ ИССЛЕДОВАНИЯ: Целью многоцентрового пилотного исследования была оценка влияния мультизональной деконтаминации носо- и ротоглотки, а также подсвязочного пространства на частоту и сроки развития ВАП, колонизацию ротоглотки и трахеи, а также клинические исходы. МАТЕРИАЛЫ И МЕТОДЫ: В многоцентровое проспективное исследование включено 60 пациентов с ожидаемой потребностью в инвазивной ИВЛ более 48 ч. Все пациенты были рандомизированно распределены в группы контроля, местного антисептика (МА) и поливалентного бактериофага (БФ). Был реализован однотипный комплекс профилактических мероприятий. Вентилятор-ассоциированные инфекционные события (ВАИС), включая ВАП, регистрировались на основании клинических, лабораторных, микробиологических, и инструментальных исследований. Диагноз ВАП считался подтвержденным при оценке по шкале CPIS ≥ 6 баллов. РЕЗУЛЬТАТЫ: Общая частота развития ВАИС достоверно не отличалась между группами и составила в группах контроля, МА и БФ 15 (75 %), 14 (70 %) и 17 (85 %) случаев соответственно. Частота развития ВАП была достоверно ниже в группах МА и БФ по сравнению с контролем: по три случая в группах МА и БФ (по 15 %) и 10 случаев (50 %) в группе контроля (χ2 = 8,35; p = 0,015). Снижение абсолютного и относительного риска ВАП при назначении МА и БФ составило 35 и 70 % соответственно. Общая летальность составила 30 %, не отличаясь достоверно между группами. При развитии ВАП отмечена тенденция к повышению летальности в сравнении с неосложненной ИВЛ. Выявлена тенденция к повышению частоты вентилятор-ассоциированного трахеобронхита в группе БФ и бессимптомной колонизации в группах МА и БФ (p = 0,07). Не выявлено различий по продолжительности инвазивной ИВЛ и госпитализации в отделение интенсивной терапии и стационаре. ВЫВОДЫ: Применение комбинированной мультизональной деконтаминации верхних дыхательных путей, включая подсвязочное пространство, c использованием октенидина и бактериофага позволяет снизить риск развития ВАП, но не изменяет частоту ВАИС. Деконтаминация может влиять на состояние микробиома дыхательных путей

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

Funding Information: The study was supported by grant ZP 10/2013 from Rigas Stradins University. Publisher Copyright: © 2016 Ozolina, Sarkele, Sabelnikovs, Skesters, Jaunalksne, Serova, Ievins, Bjertnaes and Vanags.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 were patients with PaO 2 /FiO 2 < 300 mmHg admitted to the intensive care unit (ICU) for mechanical ventilation for 24 h, or more, because of one or more disease conditions associated with increased risk of developing ARDS. Exclusion criteria were 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 (tissue) and on third (T 3 ) and seventh day (T 7 ) of the ICU stay with non-parametric statistics inclusive their sensitivity and specificity associated with the development of ARDS using receiver operating characteristic curve analysis. Statistical significance: p < 0.05. Results: Of 24 patients at risk, 6 developed mild ARDS and 4 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 PaO 2 /FiO 2 , and positive end-expiratory pressure 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. Conclusion: This pilot study showed that increased plasma concentrations of TF and PAI-1 might support ARDS diagnoses in mechanically ventilated patients after 7 days in ICU.publishersversionPeer reviewe

Целенаправленная дегидратационная терапия при сепсисе и остром респираторном дистресс-синдроме под контролем волюметрического мониторинга гемодинамики

The aim of our study was to improve results of treatment of critically ill patients with sepsis and acute respiratory distress syndrome (ARDS) using the goal-directed dehydration therapy (DT).Sixty adult patients with sepsis and ARDS receiving mechanical ventilation for at least 24 hours were enrolled into a prospective randomized study. The patients were randomized into groups of dehydration guided either by extravascular (group of extravascular lung water index ‒ EVLWI, n = 30) or intravascular (group of global end-diastolic volume index ‒ GEDVI, n = 30) compartment. Dehydration was performed over 48 hours by administering diuretics or controlled extracorporeal ultrafiltration. We measured ventilation parameters, blood gases, and parameters of volumetric monitoring. The baseline characteristics of the patients did not differ between the groups. By 48 hours, the target fluid balance was achieved in both groups. In the EVLWI group at 48 hours, we found reduction of EVLWI by 15.4% (p &lt; 0.001) and increase in PaO2/FiO2 by 23.3% as compared with baseline (p &lt; 0.001). In parallel, we observed decrease in creatinine and urea (p &lt; 0.05). In the GEDVI group, PaO2/FiO2 rose by 12.5% (p = 0.021), whereas EVLWI remained unchanged (p = 0.4). Maximal decrease in EVLWI and improvement of PaO2/FiO2 were achieved in direct ARDS.Thus, in patients with sepsis and ARDS the de-escalation goal-directed therapy resulted in the improvement of arterial oxygenation and organ function. The efficacy of dehydration was increased in direct ARDS. The extravascular compartment dehydration algorithm attenuated pulmonary edema and acute kidney injury more efficiently. Therefore, sepsis-induced ARDS may require personalized therapeutic approach.Цель: улучшение результатов лечения пациентов с сепсисом и острым респираторным дистресс-синдромом (ОРДС) путем применения целенаправленной дегидратационной терапии.Материал и методы. В проспективное рандомизированное исследование включено 60 пациентов с сепсисом и ОРДС, находившихся на искусственной вентиляции легких (ИВЛ) не менее 24 ч. Пациенты были рандомизированы в группы дегидратации под контролем внесосудистого (группа индекса внесосудистой воды легких ‒ ИВСВЛ, n = 30) или внутрисосудистого сектора (группа индекса глобального конечного диастолического объема ‒ ИГКДО, n = 30). Дегидратацию проводили в течение 48 ч путем назначения диуретиков либо аппаратной ультрафильтрации. У всех пациентов оценивали параметры вентиляции, газовый состав артериальной крови, а также показатели волюметрического мониторинга. Исходные характеристики пациентов не различались между группами.Результаты. К 48 ч целевой гидробаланс был достигнут в обеих группах. В группе ИВСВЛ к 48 ч наблюдали снижение ИВСВЛ на 15,4% (p &lt; 0,001), а также повышение PaO2/FiO2 на 23,3% от исходных значений (p &lt; 0,001), параллельно с этим отмечали снижение уровня креатинина и мочевины (p &lt; 0,05). В группе ИГКДО показатель PaO2/FiO2 увеличился на 12,5% (p = 0,021), в то время как значение ИВСВЛ не изменялось (p = 0,4). Максимальное снижение ИВСВЛ и повышение PaO2 /FiO2 достигнуты при прямом ОРДС.Выводы. Целенаправленная дегидратационная терапия у пациентов с сепсисом и ОРДС приводит к улучшению оксигенации и органной функции, при этом эффективность дегидратации выше при прямом ОРДС. Алгоритм дегидратации по внесосудистому сектору позволяет добиться более адекватной коррекции отека легких и острого повреждения почек. Вместе с тем при сепсис-индуцированном ОРДС необходим персонифицированный подход к коррекции волемического статуса