The Role Of Global End Diastolic Volume And Extravascular Lung Water In Fluid Resuscitation In Patients With Septic Shock

Objective:Severe sepsis and septic shock has become the primary cause of death of patients in non cardiac care unit. The Angus and his colleague’s study including all patients discharged from hospital in America in1995showed:there are750,000severe systemic infections each year, accounting for3/1,000of the total population and2to11%of inpatients, of which3%developed septic shock, and the mortality of severe sepsis in the hospitalized patients is up to30%, and inpatients with septic shock50to60%. Disordered Hemodynamics is the most prominent manifestation of severe sepsis and septic shock. Dysfunction of peripheral vascular systolic and diastolic is the basis of abnormal hemodynamics in patients with severe sepsis and septic shock, leading to the abnormal distribution of blood flow. Due to the alteration in expansion and permeability of blood vessels, which could lead to hypovolumic status and make it essential to evaluate and deal with the hypovolumic status which might exist possibly. Early hemodynamic support in patients with septic shock will improve hemodynamic stability, improve organ perfusion, reverse organ dysfunction and reduce the mortality rate. In this study,46patients with severe sepsis and septic shock were enrolled, hemodynamic monitoring was performed respectively, and the data including central venous pressure (CVP), global end diastolic volume index (GEDVI), stroke volume index (SVI), extravascular lung water index (EVLWI) and oxygenation index were collected, and the correlationship were analyzed, the clinical values and significance were evaluated to guide the fluid resuscitation in patients with septic shock.Method:46cases with severe sepsis/septic shock hospitalized from Jan,2011to Jun,2013were admitted. All patients were from the Critical Care Department, Zhujiang Hospital, Southern Medical University. Using retrospective case analysis method, hemodynamic data, including CVP, GEDVI, SVI, EVLWI and PaO2/FiO2were collected.8sets of data were collected in each patient in average. When SVI, GEDVI and EVLWI were collected, CVP and blood gas analysis were also performed at the same time. The data from PiCCO were taken as the gold standard, the correlationship between CVP and SVI, GEDVI and SVI, CVP and EVLWI, CVP and PaO2/FiO2were analyzed.1. Placement of central venous catheter:Central venous catheterization (internal jugular or subclavian vein) using the Seldinger’s method was performed in all patients. The apex of the triangle formed by the heads of the sternocleidomastoid muscle and the clavicle was chosen as the puncture point in internal jugular vein puncture. The needle was maintained at an angle of45°-60°above the coronal plane as it is advanced past the apex of the triangle, with the longitudinal axis in the direction of the ipsilateral nipple. The vein was generally encountered approximately2.5to3.0cm under the skin. Central venous catheter was generally placed and fixed at a depth of12to13cm. The skin was punctured approximately1cm caudal to the junction of the medial and middle thirds of the clavicle in the subclavian vein. The needle was advanced beneath the clavicle parallel to the frontal (horizontal) plane and directed toward the ipsilateral sterna notch. The needle was advanced to a depth of3to5cm. Central venous catheter was generally placed and fixed at a depth of12to14cm. Central venous catheter was connected to the transducer and monitor, patients were placed in supine position. The zero point of the transducer should be on the same lever as the fourth intercostals space midaxillary line, with flow from the transducer open to air, but closed to the patient. Monitor was set to zero. And turned the t cock so the solution in transducer flow to the patient. Recorded the lever at the end of expiration.2. Placement of PiCCO (Pulse index Continuous Cardiac Output) catheter: Femoral artery catheterization (internal jugular or subclavian vein) using the Seldinger’s method was performed in all patients. Palpated the femoral artery at about1.5to2cm below the inguinal ligament. The needle was maintained at an angle of15°to30°above the coronal plane. The needle was advanced to a depth of2to3cm. PiCCO catheter was completely inserted and fixed. One side of the catheter connected with the transducer and the monitor, was used to monitor arterial pressure; and the other side was connected to the PiCCO device.3. Cardiac output (CO) calibration:PiCCO technology is the combination of the pulse contour analysis and the transpulmonary thermodilution method. On the one hand, parameters of the pulse contour analysis, such as continuous cardiac output (CCO), stroke volume (SV) should be modified by cardiac output temperature dilution method; On the other hand, intrathoracic blood volume (ITBV), global end diastolic volume (GEDV), extravascular lung water (EVLW) and other parameters are measured by the transpulmonary thermodilution method. With the PiCCO technology the indicator (15ml of0to4℃0.9%normal saline) was injected rapidly into the circulation from the central venous catheter thrice, and data from consecutive3times of injections were calculated respectively, and averaged. Parameter errors were held within a range of10%.4Data acquisition:4.1The clinical information of all patients’were recorded, including name, gender, age, weight, patient identification number, the primary admission diagnosis, underground disease, treatment measures (including mechanical ventilation, continuous renal replacement therapy and the dose of vasoactive drugs), prognosis index(including ICU and hospital stay, ICU and hospital mortality), acute physiology and chronic health evaluation (APACHE II).4.2Circulation index:the heart rate (HR), mean arterial pressure (MAP), SVI, CVP, GEDVI, EVLWI and PaO2/FiO2.4.3Blood gas analysis:the artery blood gas analysis was performed, pH value, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2) and arterial oxygen saturation (SaO2), were calculated and recorded, meanwhile the oxygenation index (PaO2/FiO2) was also recorded.4.4Statistical:all the data were processed by SPSS19.0statistical software, the measurement data were tested by the Kolmogorov-Smimov method for normality, normal distribution data were expressed as mean±standard deviation (x±s). The correlationship among CVP, GEDVI, SVI, EVLWI and PaO2/FiO2were analyzed by Pearson linear correlation analysis, Statistical significance (two-side test) was considered as P<0.05.Results:1. Analysis on290sets of data showed that, there was no correlationship between CVP and SVI (r=-0.021, P=0.126). According to early fluid resuscitation treatment strategy in《Surviving Sepsis Campaign2012》, using a cut off8mmHg and12mmHg of CVP for further stratification, analysis of the correlation between CVP and SVI showed, in group of CVP>12mmHg, r=-0.247, P=0.101, in group of CVP<8mmHg, r=-0.196, P=0.011, and in group of8mmHg≤CVP≤12mmHg, r=0.167, P=0.151.2. Analysis on367sets of data showed that, there was a correlation between CVP and GEDVI:r=0.137, P=0.009. Subgroup was divided using a cut off8mmHg and12mmHg of CVP for further stratification of the correlation between CVP and GEDVI. In group of CVP<8mmHg, the correlation coefficient r=0.149, P=0.029. In group of8mmHg≤CVP≤12mmHg,r=0.075, P=0.462. And in group of CVP>12mmHg,r=0.049, P=0.726.3. Taking SVI as the reference index to evaluate cardiac preload and volume status, to analyze the correlation between GEDVI and SVI, we found that correlation coefficient r=0.267,P=0.000.4. The correlation coefficient between CVP and EVLWI was r=0.040, P=0.445. Using a cut off8mmHg and12mmHg of CVP for further stratification, analysis of the correlation between CVP and EVLWI showed, in group of CVP<8mmHg, r=0.221,P=0.001. In group of8mmHg≤CVP≤12mmHg,r=-0.047, P=0.646. In group of CVP>12mmHg,r=0.042, P=0.765.5. Analysis on367sets of data showed, correlation between CVP and oxygenation index was r=-0.203, P=0.000. Using a cut off8mmHg and12mmHg of CVP for further stratification, analysis of the correlation between CVP and oxygenation index showed, in group of CVP<8mmHg, r=-0.261, P=0.000. And in group of3mmHg≤CVP≤12mmHg, r=-0.003, P=0.980, and r=-0.035, P=0.805in group of CVP>12mmHg.6. Analysis on367sets of data showed, correlation between EVLWI and oxygenation index was r=-0.397, P=0.000. Using a cut off7ml/kg of EVLWI for further stratification, analysis of the correlation between EVLWI and oxygenation index showed, in group of EVLWI≤7ml/kg, r=0.021, P=0.834. While in group of EVLWI>7ml/kg, r=-0.473, P=0.000.Conclusion:1. Analysis on290sets of data showed, no significant correlation was found between CVP and SVI. Further stratified analysis showed, in group of CVP<8mmHg, there was a weak negative correlation between CVP and SVI. While in group of8mmHg≤CVP≤12mmHg and group of CVP>12mmHg, no significant correlation were found. So, CVP can not reflect the response of volume capacity accurately.2. Analysis on367sets of data showed, no significant correlation was found between CVP and GEDVI. Further stratified analysis showed that, in group of CVP <8mmHg, there was a weak linear correlation between CVP and GEDVI. While, either in group of8mmHg≤CVP≤12mmHg, or in group of CVP>12mmHg, no significant correlation was found between CVP and GEDVI. These showed that, CVP could not be used to assess the preload of the heart.3. GEDVI increases with SVI. There was a linear correlation between GEDVI and SVI. Thus, using GEDVI as the parameter to evaluate cardiac preload is more accurate and reliable than CVP.4. Analysis on367sets of data showed, There was no significant correlation between CVP and EVLWI. Further stratified analysis showed that, in group of CVP <8mmHg, there was a weak linear correlation between CVP and EVLWI. While, both in group of8mmHg≤CVP≤12mmHg, and group of CVP>12mmHg, there were no significant correlation between CVP and EVLWI. CVP can not reflect the range and level of pulmonary edema.5. Analysis on367sets of data showed, a weak negative correlation was found between CVP and oxygenation index. Further stratified analysis showed, in group of CVP<8mmHg, a weak negative correlation was found, while in group of8mmHg≤CVP≤12mmHg and in group of CVP>12mmHg, no correlation were found between CVP and oxygenation index.6. A significant negative correlation was found between EVLWI and oxygenation index. Especially, in group of EVLWI>7ml/kg, the correlationship seemed more obvious. It suggested that EVLWI might be an important factor affecting oxygenation. So, in patients with severe sepsis or septic shock, in which EVLWI≤7ml/kg, the reduction of EVLWI does not predict the improvement of oxygenation, and the factors affecting oxygenation should be considered carefully. While in which EVLWI>7ml/kg, lowering of EVLWI might reliably predict the improvement of oxygenation.In conclusion, fluid resuscitation in patients with septic shock, especially in patients with capillary leakage is necessary to ensure adequate intravascular volume and avoid the occurrence of lung edema. Accuratly, sensitive hemodynamic monitoring plays an important role, it helps the clinician to make the right decision about whether the patient needs fluid infusion or not. The monitoring technology of PiCCO is not affected by the influence of mechanical ventilation, and monitoring of cardiac output is not affected by EVLWI. Parameters from PiCCO can be used as indexes to evaluate the cardiac preload accurately in patients with mechanical ventilation and provide comprehensive hemodynamic parameters, making good understanding of circulating blood volume and pulmonary edema of patients with septic shock. CVP can’t reflect the preload of the heart and the degree of pulmonary edema. So it is not a suitable index for guiding fluid resuscitation treatment. We recommend using the PiCCO monitor to guide the fluid resuscitation in patients with shock.