Efficiency of Transpulmonary Thermodilution in the Optimization of Intensive Treatment in Patients with Severe Nosocomial Pneumonia

Цель исследования. Оценка эффективности применения транспульмональной термодилюции (ТПТД) для выбора мер по коррекции гемодинамики у больных с внебольничной пневмонией (ВП) тяжелого течения. Материалы и методы. В исследование включили 107 больных ВП, поступивших в отделение реаниматологии. Интенсивное лечение больных 1�й группы осуществляли в соответствии с протоколом коррекции гемодинамики при ранней целенаправленной тера� пии сепсиса. Во 2�й группе инфузионную терапию и назначение симпатомиметических препаратов выполняли в зави� симости от результатов ТПТД. Результаты. На момент включения в исследования больные обеих групп по изучен� ным клинико�лабораторным показателям не различались. С 1�х суток во 2�й группе «ТПТД�контролируемого» интенсивного лечения назначение симпатомиметических препаратов было практически в 2 раза более активным, чем в 1�й, а величина положительного гидробаланса, напротив, была в 2 раза меньше. К 5�м суткам частота назначения симпатомиметических препаратов не имела межгрупповых отличий, а на 7�е сутки становилась меньше у больных 2�й группы. В результате проводимого лечения в группе 2 отсутствовала необходимость в значительных объемах инфу� зии и большом положительном гидробалансе, что результировалось в меньших значениях центрального венозного давления (ЦВД). Положительный гидробаланс на 5�е сутки у больных 2�й группы был в 5 раз меньше, к 7�суткам ин� тенсивного лечения показатель у них становился отрицательным. ЦВД не имело межгрупповых различий на 1�е сут� ки, однако, начиная со 2�х суток и вплоть до конца периода наблюдения, у больных 1�й группы показатель был выше. На 5—7 сутки у больных 2�й группы были выше значения SvO 2 и ниже лактатемия. Тяжесть состояния по шкале SOFA к 3�м суткам у больных 2�й группы была несколько больше, чем в 1�й, а затем существенно снижалась и на 5—7 сутки оценка по SOFA во 2�й группе была на 2—2,5 балла ниже, чем в 1�й. Летальность в ОРИТ у больных 1�й группы соста� вила 49%, во 2�й — 33% ( χ 2 =3,899; р<0,05). Заключение. Определение объема инфузии и показаний к назначению сим� патомиметических препаратов на основании комплексной оценки показателей индекса глобального конечно�диасто� лического объема (ИГКДО), сердечного индекса (СИ) и индекса общего периферического сосудистого сопротивления (ИОПСС) результируется в улучшении клинических исходов у больных с тяжелой ВП, находящихся на искусственной вентиляции легких (ИВЛ). Такой подход позволяет патогенетически обоснованно назначать симпа� томиметические препараты и избегать чрезмерной волемической нагрузки. Ключевые слова: внебольничная пневмо� ния, транспульмональная термодилюция, интенсивное лечение. Objective: to evaluate the efficiency of transpulmonary thermodilution (TPTD) for the choice of measures to correct hemodynamics in patients with severe nosocomial pneumonia (NP). Subjects and methods. The investigation enrolled 107 NP patients admitted to an intensive care unit (ICU). Group 1 patients were intensively treated in accordance

Objective: to evaluate the efficiency of transpulmonary thermodilution (TPTD) for the choice of measures to correct hemodynamics in patients with severe nosocomial pneumonia (NP).Subjects and methods.The investigation enrolled 107 NP patients admitted to an intensive care unit (ICU).Group 1 patients were intensively treated in accordance with a protocol for hemodynamic correction during early goal directed therapy for sepsis.In Group 2, infusion thera py and sympathomimetic agents were prescribed depending on the results of TPTD.Results.Patients in both groups did not differ in the examined clinical and laboratory indicators.On day 1 of intensive therapy, in Group 2 (a TPTD controlled intensive treatment group) the prescription of sympathomimetic drugs was virtually twice more active than in Group 1; and the value of positive hydrobalance was, twice less.In 5 days, the frequency of use of sympathomimetic agents had no intergroup differences and, in 7 days became less in Group 2 patients.After the therapy patients in Group 2 did not require substantial amounts of infusion and great positive hydrobalance, resulting in lower central venous pressure (CVP) values.After 5 days of intensive therapy, the positive hydrobalance in Group 2 patients was 5 times less and on day 7 this indicator became negative.There were no intergroup differences in CVP on day 1; how

Introduction
The problem of effective treatment of severe pneu monia is one of the most relevant for the modern resusci tation [1][2][3][4][5].Despite the introduction of modern antibacterial drugs and improved methods of intensive treatment, mortality from community acquired pneumo nia (CAP) remains high [6,7].Threatening complication of VP include circulatory disorders [8], which remain the leading cause of death [9,10].Development of hemody namic disorders in patients with CAP ensures the need in active infusion therapy and treatment with sympath omimetic vasopressors and cardiotonics [10], however, clear recommendations for the clinical situation are absent.In recent years the attention of clinicians was attracted to employment of techniques of transpul monary thermodilution (TPTD) to optimize treatment strategies in patients with sepsis and acute respiratory distress syndrome (ARDS) [11].This approach has demonstrated to be clinically efficient in several other clinical situations [12,13], however, the experience of its use in patients with CAP was limited.
This study was designed to evaluate the efficacy of TPTD for selecting parameters of hemodynamics correc tion in patients with severe course of CAP.

Materials and Methods
Prospective randomized study included 107 patients with CAP admitted to the Intensive Care Unit (ICU).The study was confirmed by a local ethical committee.All patients provided written informed consent for the study.Criteria for inclusion of patients in the study were as follows: • older than 18 and younger than 70 years old; • confirmed diagnosis of CAP; • testimony for a top ventilation decompensated respira tory failure with a reduction in oxygen saturation below 90% while being on oxygen therapy and the index PaO 2 / FiO 2 less than 200 mm Hg); • mean arterial pressure (MAP) below 65 mmHg on the first day of admittance at the ICU.
Exclusion criteria were as follows: failure of left ventricular function by clinical data, the presence of absolute or relative con traindications to the femoral artery catheterization (severe ather osclerotic lesions of the femoral artery, hypocoagulation pyoder mia with a hypocoagulation in the proposed puncture site); severity of a condition by APACHE II> 26 points; severe con comitant sub and decompensated pathology of the lungs, heart, kidneys, liver, diabetes, cancer, acquired immune deficiency syn drome.
All patients received an identical starting antibacterial treat ment and infusion of crystalloid solution (Ringer's sodium chlo ride, 0.9%) with, no blood transfusions performed..
Intensive treatment of patients in group 1 was carried out in accordance with the protocol for hemodynamics correction in early targeted therapy of sepsis [15] that aimed to achieve the tar get values of central venous pressure (CVP) of 8-12 mm Hg, mean arterial pressure (MAP) 65-80 mm Hg if necessary by assigning vasoactive substances and ensuring saturation of the venous blood (SvO 2 ) more than 70%.
In group 2, infusion therapy and prescription of sympath omimetic drugs was performed according to the results of TPTD.The final goal was to ensure the index value of the global end dias tolic volume (GEDI) within the 680-800 ml/m 2 range; indica tions for sympathomimetic drugs with cardiac effects were expect ed to result in decreasing the cardiac index (CI) to less than 2.5 L/min/m 2 , whereas vasopressors should decrease total peripheral vascular resistance (SVRI) to less than 1700 dyne•s•cm 5 •m 2 .
All the patients at admission to the Intensive Care were per formed with the catheterization of a trunk vein (subclavian and/or internal jugular) and femoral artery.Patients in Group 1 with femoral artery catheters were monitored for blood pressure by patient monitoring system (Draeger Medical Inc., PA, USA).In group 2, catheterization of the femoral artery catheter was per formed by Pulsiocath PV2015L204F (firm «Pulsion Medical Systems»), which was connected to a monitor system PiCCO plus («Pulsion Medical Systems»).TPTD was performed by stan dard methods.
Parameters were monitored upon admission of patients in the ICU prior to mechanical ventilation, then on days 2, 3, 5 and 7 during the intensive treatment.All the patients were monitored for MAP, CVP, heart rate (HR), SvO 2 , lactate levels in the venous blood, daily hydrobalance, frequency of administration and dosage of sympathomimetic drugs, and severity of the condition ( SOFA scale).The values of SI, stroke volume index (SVI) GEDI and SVRI were recordered in patients of group 2 (stages 2-5).
The data were statistically processed and calculation of mean values and standard deviations (у), midrange features (P) was per formed.Significance of differences depending on the nature of dis tribution of the variables were assessed by Student t test or non parametric chi square test.
Comparing the hemodynamic profile of patients, it should be stressed that in the 1 st group, intensive treat ment in which it is conducted in accordance with the pro tocol of early targeted therapy of sepsis, circulation system was in general satisfactory.Starting from 2 days of treat ment it was possible to provide reference values of MAP and SvO 2 .The most important therapeutic measure in this case was an infusion to achieveo positive hydrobalance and the use of sympathomimetic drugs in half of the cases.Positive hydrobalance was maintained up to 7 days of observation, the frequency of prescription of sympath omimetics was virtually unchanged.In a group 2 patients a comprehensive analysis of GEDI, SI, and defined SVRI resulted in more sympathomimetic drugs usage than in group 1, and the amount of positive hydrobalance thus became twice less.The need for a more active sympath omimetic therapy persisted up to the third day of observa tion, and on days 5-7 it began to decrease substantially in step 5 to become more rare curative measure than in group 1.In this case, there was no need in infusions of large volumes to keep positive hydrobalance that resulted in lower values of CVP.Comparative evaluation of intergroup SvO Таблица 1. Клинико лабораторные показатели у обследованных больных.Table 1.Clinical and laboratory parameters in patients.
In our study, TPTD resulted in avoiding the exces sive infusion and provided zero or even negative hydrobal ance on day 7 of intensive treatment.Unfavorable patho genic role of hydration in patients in critical illness has been widely discussed [16,17] indicating that it might interfere with the function of the lungs leading to adverse outcomes.It is likely that this pathological effect is typical for patients with severe CAP.It is believed that the decrease in overhydration contributes to improving the clinical outcome.
TPTD added to standard monitoring allows not only to react to changes in SI round, but also to correct the vol ume of infusion for optimal hydrobalance while achieving an adequate level of tissue perfusion leading to the restora tion and maintenance at a certain level of tissue oxygen delivery, which was manifested with an increase in SvO 2 .Known level of the latter is considered as an important indicator of adequacy of oxygen delivery to the cells of the body [18].In addition, accumulation of lactate in the blood provided an additional information about inadequate per fusion of tissues and organs.Hyperlactatemia is a valuable predictor of survival in sepsis [19].Both of these indicators in patients receiving «TPTD controlled» correction hemodynamics were kept at the «best levels» versus stan dard therapy.
Evaluation of TPTD values (Table 2) showed that in patients of group 2 the SR values were increasing to 5 th day at a median of 0.7 l/m/m 2 mainly due to SVI, to which at the 5 th day the val;ues were 9 4 ml/m 2 greater than at the baseline.Initially, lowered GEDI during the observation period was within the normal range, although a slight increase was traced on 5-7 th days.Initially lowered SVRI values were almost normalized by day 3 and remained at this level until the end of the study.The TPTD results sug gest that hemodynamic improvement in the patients occured by improving the pumping function of the heart thus increasing the initially reduced vascular tone.
There is a good reason to believe that an increase in the pumping function of the heart, improved oxygen trans port and tissue perfusion in patients treated with sympath omimetic drugs by prescription to objectify the deployment

Parameters
Values of parameters at the stages of the study, days

Заключение
Таким образом, определение объема инфузии и показаний к назначению симпатомиметических пре of TPTD, were the factors that determined the reduction in severity of symptoms in patients at day 7 of treatment and a decreasing the mortality in the ICU to 16%.

Conclusion
Thus, determination of the infusion and indications for prescription of sympathomimetic drugs on the basis of a comprehensive assessment of indicators GEDI, CI and SVRI results in an improved clinical outcome in patients with severe CAP and mechanical ventilation.This approach allows the pathogenetically reasonable prescrip tion of sympathomimetic drugs, the increased demand of which becomes evident starting from the first days of intensive treatment and which allows to avoid the exces sive volume load.TPTD is appropriate to be included in hemodynamic monitoring in severe CAP, especially in patients with impaired hemodynamics.

Parameters Values of parameters at the stages of the study (days) in groups
5 day of treatment there was no intergroup difference in the fre w w w .r e a n i m a t o l o g y .c o m