Vsevolod V. Kuzkov

Extravascular lung water determined with single transpulmonary thermodilution correlates with the severity of sepsis-induced acute lung injury

Objective:To find out if the extravascular lung water index (EVLWI) and the derived permeability indexes determined by the single transpulmonary thermodilution technique are associated with markers of acute lung injury in human septic shock. Design:Prospective, observational study. Setting:Mixed intensive care unit of a 900-bed university hospital. Patients:Thirty-eight consecutive adult patients with septic shock and acute lung injury. Interventions:None. Measurements and Main Results:The variables were assessed over a 72-hr period and included hemodynamics, EVLWI, and pulmonary vascular permeability indexes determined with the single indicator transpulmonary thermodilution technique, lung compliance, oxygenation ratio (Pao2/Fio2), lung injury score, cell counts, and the plasma concentration of endothelin-1. At day 1, EVLWI was elevated (≥7 mL/kg) in 28 (74%) patients and correlated with lung compliance (r = −.48, p = .002), Pao2/Fio2 (r = −.50, p = .001), lung injury score (r = .46, p = .004), roentgenogram quadrants (r = .39, p = .02), and platelet count (r = −.43, p = .007). At day 3, EVLWI correlated with compliance (r = −.51, p = .002), Pao2/Fio2 (r = −.49, p = .006), and lung injury score (r = .53, p = .003). At day 3, EVLWI and pulmonary vascular permeability indexes were higher in nonsurvivors (p< .05). The plasma concentration of endothelin-1 (mean ± sd) was significantly higher in patients with elevated EVLWI (≥7 mL/kg) (3.85 ± 1.40 vs. 2.07 ± 0.38 pg/mL, respectively). Twenty-two (59%) patients died before day 28. Conclusions:In human septic shock, EVLWI demonstrated moderate correlation with markers of acute lung injury, such as lung compliance, oxygenation ratio, roentgenogram quadrants, and lung injury score. In nonsurvivors, EVLWI and permeability indexes were significantly increased at day 3. Thus, EVLWI might be of value as an indicator of prognosis and severity of sepsis-induced acute lung injury.

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

IntroductionAcute 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 (EVLWST) and postmortem gravimetric (EVLWG).MethodsEighteen instrumented and awake sheep were randomly assigned to one of three groups. All groups received Ringers 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 EVLWST, were measured using a PiCCOplus monitor (Pulsion Medical Systems, Munich, Germany), and the last measurement of EVLWST was compared with EVLWG.ResultsAt the end of experiment, values for EVLWST (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 EVLWIG were 6.2 ± 0.3, 7.1 ± 0.6 and 11.8 ± 0.7 ml/kg (P < 0.05). Ranges of EVLWIST and EVLWIG values were 7.5–21.0 and 4.9–14.5 ml/kg. Regression analysis between in vivo EVLWST and postmortem EVLWG yielded the following relation: EVLWST = 1.30 × EVLWG + 2.32 (n = 18, r = 0.85, P < 0.0001). The mean bias ± 2 standard deviations between EVLWST and EVLWG was 4.9 ± 5.1 ml/kg (P < 0.001).ConclusionIn 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.

Single transpulmonary thermodilution and continuous monitoring of central venous oxygen saturation during off-pump coronary surgery.

Background: Off‐pump coronary artery bypass grafting (OPCAB) requires thorough monitoring of hemodynamics and oxygen transport. Our aim was to find out whether therapeutic guidance during and after OPCAB, using an algorithm based on advanced monitoring, influences perioperative hemodynamic and fluid management as well as the length of post‐operative ICU and hospital stay.

Perioperative haemodynamic therapy.

Purpose of reviewTo discuss the perioperative monitoring tools and targets for haemodynamic optimization and to assess the influence of goal-directed therapy (GDT) on organ function, complications and outcome in different categories of surgical patients. Recent findingsThe choice of perioperative haemodynamic monitoring for GDT depends on the surgery-related and the patient-related risk. Conventional monitoring and minimally invasive approaches can be used for perioperative optimization of low-risk to moderate-risk patients. Thermodilution methods and continuous cardiac output/oxygen transport monitoring are the most reliable techniques for major surgery and high-risk/unstable patients. An important goal of perioperative haemodynamic therapy is to maintain cardiac function and organ perfusion, optimizing the balance between oxygen delivery and consumption. Several studies, using different monitoring tools and end-points, have shown that GDT provides optimal haemodynamic performance, improves organ function, reduces the number of complications and time to ICU and hospital discharge and decreases the mortality rate in high-risk surgical patients. SummaryGDT provides a number of benefits in major surgery. Based on adequate monitoring, the goal-directed algorithms facilitate early detection of pathophysiological changes and influence the perioperative haemodynamic therapy that can improve the clinical outcome. The perioperative GDT should be early, adequate and individualized for every patient.

Extravascular lung water after pneumonectomy and one-lung ventilation in sheep

Objective:To compare the single thermodilution and the thermal-dye dilution techniques with postmortem gravimetry for assessment of changes in extravascular lung water after pneumonectomy and to explore the evolution of edema after injurious ventilation of the left lung. Design:Experimental study. Setting:University laboratory. Subjects:A total of 30 sheep weighing 35.6 ± 4.6 kg. The study included two parts: a pneumonectomy study (n = 18) and an injurious ventilation study (n = 12). Methods:Sheep were anesthetized and mechanically ventilated with an Fio2 of 0.5, tidal volume of 6 mL/kg, and positive end-expiratory pressure of 2 cm H2O. In the pneumonectomy study, sheep were assigned to right-sided pneumonectomy (n = 7), left-sided pneumonectomy (n = 7), or lateral thoracotomy only (sham operation, n = 4). In the injurious ventilation study, right-sided pneumonectomy was followed by ventilation with a tidal volume of 12 mL/kg and positive end-expiratory pressure of 0 cm H2O (n = 6) or by ventilation with a tidal volume of 6 mL/kg and positive end-expiratory pressure of 2 cm H2O for 4 hrs (n = 6). Volumetric variables, including extravascular lung water index (EVLWI), were measured with single thermodilution (STD; EVLWISTD) and thermal-dye dilution (TDD; EVLWITDD) techniques. We monitored pulmonary hemodynamics and respiratory variables. After the sheep were killed, EVLWI was determined for each lung by gravimetry (EVLWIG). Results:In total, the study yielded strong correlations of EVLWISTD and EVLWITDD with EVLWIG (n = 30; r = .83 and .94, respectively; p < .0001). After pneumonectomy, both the left- and the right-sided pneumonectomy groups displayed significant decreases in EVLWISTD and EVLWITDD. The injuriously ventilated sheep demonstrated significant increases in EVLWI that were detected by both techniques. The mean biases (±2 sd) compared with EVLWIG were 3.0 ± 2.6 mL/kg for EVLWISTD and 0.4 ± 1.6 mL/kg for EVLWITDD. Conclusions:After pneumonectomy and injurious ventilation of the left lung, TDD and STD displayed changes in extravascular lung water with acceptable accuracy when compared with postmortem gravimetry. Ventilator-induced lung injury seems to be a crucial mechanism of pulmonary edema after pneumonectomy.

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

IntroductionWe 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.MethodsSheep 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.ResultsAn 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.ConclusionsInhalation of aerosolised APC attenuates LPS-induced lung injury in sheep by preventing a decline in the volume of aerated lung tissue and improving oxygenation.

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

ITBVI = 1.16 × GEDVI + 92.45 ITBVI = 1.43 × GEDVI + 13.48 ITBVI = 1.21 × GEDVI + 73.72 SB, spontaneous breathing; MV, mechanical ventilation with tidal volumes of 6 to 8 ml/kg and positive end-expiratory pressure 2 cmH2O; PE, pneumonectomy; ITBVI, intrathoracic blood volume index; GEDVI, global end-diastolic volume index; PBVI, pulmonary blood volume index; ITBV, intrathoracic blood volume; GEDV, global end-diastolic volume. All data are distributed normally and are presented as means ± SD. aPearson coefficient, r (p < 0.0001). b p < 0.05 compared with SB; c p < 0.05 compared with MV (analysis of variance followed by Scheffe’s test).

Validation of cardiac output monitoring based on uncalibrated pulse contour analysis vs transpulmonary thermodilution during off-pump coronary artery bypass grafting

BACKGROUND Cardiac output monitoring, as a part of a goal-directed haemodynamic management, has been shown to improve perioperative outcome in high-risk patients undergoing major surgical interventions. However, thorough validation of cardiac output monitoring devices in different clinical conditions is warranted. The aim of our study was to compare the reliability of a novel system for cardiac index (CI) monitoring based on uncalibrated pulse contour analysis (UPCA) with transpulmonary thermodilution (TPTD) during off-pump coronary artery bypass grafting (OPCAB). METHODS Twenty patients undergoing elective OPCAB were enrolled into the study. CI measured by means of UPCA (CIUPCA) was validated against CI determined with TPTD technique (CITPTD). Parallel measurements of CI were performed at nine stages during the surgery and after operation. We assessed the accuracy and the precision of individual values and the agreement of trends of changes in CI. RESULTS Totally, 180 pairs of data were collected. There was a significant correlation between CIUPCA and CITPTD (ρ=0.836, P<0.01). According to a Bland-Altman analysis, the mean bias between the methods was -0.14 litre min(-1) m(-2) with limits of agreement of ±0.82 litre min(-1) m(-2) and a percentage error of 31%. A polar plot trend analysis revealed acceptable angular bias (-0.54°), increased radial limits of agreement (±52.7°), and decreased polar concordance rate (74%). CONCLUSIONS In OPCAB, UPCA provides accurate and precise CI measurements compared with TPTD. However, the ability of this method to follow trends in cardiac output is poor. CLINICAL TRIAL REGISTRATION NCT01773720 (ClinicalTrials.gov).

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.

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

IntroductionAcute 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.MethodsTwenty-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.ResultsOA 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.ConclusionsIn 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.