Non invasive evaluation of central venous pressure using echocardiography in the intensive care – Specific features of patients with right ventricular enlargement and chronic exacerbated pulmonary disease

1 Assistente Hospitalar de Medicina Interna, subespecialista de Medicina Intensiva / Hospital Assistant, Internal Medicine, sub-speciality Intensive Medicine 2 Interna do Internato Complementar de Pneumologia / Intern, Complementary Internship, Pulmonology 3 Assistente Eventual de Medicina Interna / Future Assistant, Internal Medicine 4 Professor Agregado da Faculdade de Medicina de Lisboa, chefe de Serviço de Cardiologia, director do Serviço de Cardiologia do Hospital de Santa Maria, Lisboa / / Institute Professor, Lisbon University School of Medicine, Head, Cardiology Unit, Director, Cardiology Unit, Hospital de Santa Maria, Lisbon


Rev Port Pneumol 2006; XII (6): 637-658
Palavras-chave: Pressão venosa central, ecocardiografia, cuidados intensivos, doença pulmonar crónica. IVC index) were performed simultaneously. Parametric and non-parametric statistical analysis was performed to establish correlations between variables. Results: 560 patients were admitted to the study, including 477 in whom IVC was analysed, aging 62.2 ± 17.3 years, a mean ICU stay 11.9 ± 18.7 days, a APA-CHE II score 23.9 ± 8.9 and a SAPS II score 55.7 ± 20.4. Through linear regression analysis CVP was influenced by IVC index (p=0.001), IVC maximum dimension (p=0.013) and presence of mechanical ventilation (p=0.002). A statistically significant correlation was found between the following parameters: an IVC index< 25% and a CVP >13mmHg; an IVC index and a CVP 26%-50%; an IVC index >51% and CVP< 7mmHg; an IVC maximum dimension > 20mm and a CVP >13mmHg; an IVC maximum dimension <10mmHg and CVP< 7mmHg. Patients with right ventricle enlargement presented a lack of agreement between IVC maximum dimension and CVP> 7mmHg was observed, and in patients with chronic respiratory failure (who presented a high prevalence of right ventricular enlargement) a lack of agreement between IVC index >50% and CVP< 7mmHg was also observed. Conclusions: IVC analysis is a possible way to noninvasively estimate CVP in a medical/surgical ICU. However, patients with right ventricular enlargement and admitted with chronic respiratory failure present a lack of agreement between IVC parameters and low values of CVP. IVC dimension is a marker of chronic disease and IVC index correlated better with CVP.

Introduction
Measuring volemia is a crucial step in assessing the state of health of a patient, particularly a patient in an intensive care unit (ICU). Central venous pressure (CVP) is one of the methods frequently used to measure volemia, both in ICU and in other locations. It lost ground to the use of pulmonary artery occlusion pressure for a while 1,2 , but several recent different clinical trials have referred to it as a test indicative of volemia. They attribute the same target-values to it as to fluid therapy 3,4 , or show this technique has the same weight in prognosis as other invasive procedures 5 . Echocardiography can be used as a noninvasive technique to obtain haemodynamic parameters 6 , one of which is CVP. The relationship between the inferior vena cava (IVC) and the CVP was established over 20 years ago 7,8 . These original studies show that diseases which affect the right heart can be identified by the repercussions in this vascular structure. On the other hand, the work undertaken on haemodialysis patients has allowed a link to be forged between IVC characteristics and intravascular volemia. This has made it possible to measure the dry weight by variables derived from the analysis of the IVC 9-12 . Analysing the IVC's respiratory kinetics allows a close analysis to be made of the venous return and the resistance met by the blood entering the right auricular. Some authors call this the "starling resistor" 13 . The importance of this parameter has been underestimated in intensive care units. In their study, Jue et al 14  We aimed to analyse the impact of other echocardiographic and clinical parameters on the IVC as a way of evaluating the impact of TTE as part of a non-invasive haemodynamic evaluation.

Patients
The study population comprised patients whose CVP was measured via central venous catheters which are suitably located (jugular or subclavian central venous catheters n=560). The subjects had also undergone an echocardicac exam in the first 24 hours following admission. The study ran from August 2002-December 2005.
The following parameters were used to characterise the patients' clinical and demographic profile: age, gender, length of ICU hospitalisation, mortality, median arterial pressure, cardiac rate and APACHE II and SAPS II severity indexes and the most representative diagnostic groups. The patients' diagnostics were defined prospectively, following the pathologies referent to the organs and organ systems or with a representative patient number.

Echocardiography
The echocardiograph variables taken into account for analysis were: measurement of the diameter of the left ventricle (LV),

Statistical analysis
The statistical description was the obtaining of the medians and standard deviation for each of the variables. The Student 'T' test was used to analyse the differences between the groups of variables studied. The Mann-Whitney test was used whenever a non-normal distribution occurred. The echocardiograph variables studied (cavity diameters, presence of systolic dysfunction, maximum diameter and index of the inferior vena cava) were studied according to their influence on the CVP. To establish the influence on the CVP, a linear regression with a numerically variable CVP as a variable dependant on the stepwise backward procedure was used. Linear correction tests and the chi-squared non-parametric test were used to analyse the correlations between the variables and the CVP. A value of p> 0.05 for a 95% confidence interval and a value of r> 0.85 in the Pearson correlation were considered statistically significant. VCIi (%) 28,4 ± 24,2 Mechanical ventilation also influenced the CVP (p=0.002) and allowed for strongerbut not statistically significant -correlations between the CVP and the diameter of the RV (p=0.071) and the RA (p=0.099).

Correlation between the CVP and the ICV index
To use the comparative analysis of the nonparametric chi-squared test, the variable CVP was categorised under 3 variables: below 7mmHg, between 8 and 12mmHg and above 13mmHg and the IVC index was divided into 3 categorical variables: from 0% -25%, from 26% -50% and over 51%. Analysing the set of patients showed that 111 patients (23.2%) had an index below 25%, 139 (29.1%) had an index between 26 and 50% and 225 (47.2%) had an index over 51%.  In analysing the two variable categories, the CVP and the IVC index, using the chisquared test gave a value <0.001. For a value of r the Pearson correlation test was 0.565 and the Spearman correlation was 0.592. This correlation is shown for the majority of the patients in the dispersion graph in Fig. 3. This figure shows that some patients with high IVC indexes had equally high CVPs.
Mechanical ventilation and the diameter of the RV influence the CVP. The correlations between these 2 parameters in these 2 groups of patients are shown in Table IV. It is seen that the correlation of the ventilated patients was less than in the non-ventilated patients and was markedly less in the patients with RV enlargement.   (Fig. 4), denotando uma ausência de correlação entre estes dois parâmetros nesta faixa de valores (p não significativo).
A correlation was also seen between the IVC index and the CVP in the patients admitted to hospital for worsening of chronic pulmonary disease. These had a greater rate of RV enlargement (35 out of the 63 patients, 54%). Out of this group of patients, only 5 had CVP values of <7mmHg and 5 had an IVC index of > 50%. While only a few patients fell into the lowest CVP band (n=5) or into the highest IVC index band (n=5), there was a great dispersion of values in this interval (Fig. 4), denoting an absence of correlation between these 2 parameters in this band of values (p non-significant).

Correlation between the CVP and the maximum diameter of the IVC
The non-parametric chi-squared test showed a statistically significant correlation between IVC enlargement (maximum diameter> 20mm) and CVP values> 13mmHg, and an IVC with a diameter less than 10mm and CVP < 7mmHg (Table V).

Discussão
Estudos prévios e principais achados Não encontrámos na literatura estudo semelhante realizado numa UCIP e com um número semelhante de doentes. Mesmo o estu-It can be seen that this correlation is steady in the ventilated patient group and in the patients with worsening of chronic pulmonary disease. In addition, it was seen that the patients with RV enlargement had a frequency of ICV diameter values <10mm lower (n=7.8.1%) while 57.7% (n=45) had an IVC of > 20mm. Four of these patients had CVP of <7mmHg (Table VI).

Other correlations
To analyse the linear regression with the IVC index and the maximum diameter of the IVC as dependant variables, it is seen that the maximum diameter correlates with the enlarged RV and with the IVC index (p <0.001 and p=0.03 respectively). No relation was seen between the IVC index and the abovementioned echocardiograph parameters, however.

Earlier studies and main findings
We could find no comparable earlier study carried out in a PICU and with a similar number of patients. Even the Jue et al study Avaliação não invasiva da pressão venosa central por ecocardiografia em cuidados intensivos -particularidades nos doentes com dilatação do ventrículo direito e exacerbação de doença pulmonar crónica Paulo Marcelino, Alexandra Borba, Ana Paula Fernandes, Susan Marum, Nuno Germano, Mário G Lopes do de Jue e col incluiu apenas 49 doentes ventilados, nos quais não foram avaliadas a influência de determinados parâmetros ecocardiográficos, em particular a dilatação do VD ou a presença de doença pulmonar crónica. Observámos uma fraca correlação linear entre estas variáveis, já descrita na literatura 18 , mas uma possibilidade de aferir qualitativamente a PVC por ETT, em especial nos seus valores extremos. Deparámos com duas dificuldades principais relativamente à obtenção de dados. A primeira tem a ver com a dificuldade na visualização da VCI, que na sua maioria se deveu à presença de pensos abdominais nos doentes cirúrgicos, inviabilizando um conjunto de exames. Ainda nestes doentes, a presença de líquido intra-abdominal de natureza diversa (inflamatória ou não) e a interposição de ansas intestinais dificultaram a visualização de estruturas intrabdominais, entre as quais a veia cava inferior. Contudo, o sucesso alcançado parece significativo, pois mais de 80% dos doentes puderam ser avaliados. Este sucesso parece--nos ser de valorizar na perspectiva de uma possível utilização sistemática da avaliação da VCI neste grupo particular de doentes. Por outro lado, em alguns doentes, observou-se um conflito assinalável entre os dados da PVC e da VCI, uma vez que em alguns obtivemos valores baixos de PVC e valores elevados de índice da VCI. Este conflito não comprometeu a correlação geral, que se manteve significativa para a generalidade dos doentes, em especial por análise estatística com métodos não paramétricos, reforçando aliás o carácter essencialmente qualitativo da informação obtida por ETT. Podemos apontar diversas causas para este facto. Apesar do cuidado observado com a visualização do posicionamento dos cateteres centrais utilizados para determinação da PVC e do cui-population only had 49 ventilated patients and of these, the influence of determined echocardiograph parameters, in particular RV enlargement or the presence of chronic pulmonary disease, were not evaluated. We saw a weak linear correlation between these variables, as has already been seen in earlier studies 18 , but there was the chance of measuring the CVP qualitatively by TTE, particularly its most extreme values. There were two main difficulties inherent in obtaining these data. The first had to do with the difficulty of visualising the IVC, which was largely due to the surgery patients having abdominal plasters which made it impossible to carry out certain exams. Intrabdominal liquid (inflammatory or non-inflammatory) in these surgery patients and the interposition of intestinal ansas made it hard to visualise the intrabdominal structures, one of which is the inferior vena cava. This notwithstanding, the success achieved seems significant in that it was possible to evaluate over 80% of these patients. We feel this success makes it possible to evaluate the ICV of this particular group of patients in a systemic way. On the other hand, a marked conflict was seen in some patients between the CVP and IVC data, in that we obtained low CVP values and high ICV index values in some patients. This division did not compromise the general correlation which remained significant for the majority of patients, in particular for a statistical analysis with non-parametric methods. This served to strengthen the essentially qualitative character of the information gleaned through TTE. There are several causes for this. Despite the care taken with visualising the positioning of the central catheters used for determining the CVP and the care taken in measuring this parameter, it was not possible to evaluate the exact location of the measurement, unlike that which is made possible by TTE. On the other hand, as CVP is a pressure parameter it cannot be perfectly related with volemia 19 . In determining the IVC parameters, as the IVC is a vein which distends, it is not only a part of the patient's volemia, but also rebounds pressure to the pulmonary circulation. If under normal conditions this is the low pressure circulation, under pathological conditions this relationship can change and in these cases it is the IVC rather than the volemia which better mirrors the overload of pressure.
We saw that both the CVP and the parameters used to measure the IVC changed in the same way (or rather a greater CVP corresponds to a lower IVC index) in the patients more likely to show changes in the pulmonary circulation pressure, i.e. ventilated patients or patients with RV enlargement. Whatever the case, elevated pulmonary circulation pressure impacts on the correlation quality of these 2 parameters.
A clinical perspective evaluation of the data Patients with RV enlargement show a weaker relationship in the qualitative appreciation of the CVP through the maximum diameter of the IVC. These data come from earlier studies made and from them we can infer that under these conditions an analysis of the IVC preferentially reflects the chronic overload condition of the right cavities. As the patient population with worsened chronic pulmonary disease is essentially affected by RV enlargement (54% in our study), it is not strange that the conclusion should be similar in this group of patients. A chronic physiological overload of the pulmonary circulation has been seen in highly trained athletes. The authors of a study into competition athletes and swimmers subject to chronic right overload and respective pulmonary circulation overload caused by physical effort describe an increased maximum IVC diameter but with the respective index values above 50%, close to normal values seen in normal individuals 11,20 . This suggests that a chronic overload fundamentally alters the maximum diameter of the IVC and the IVC index reflects better the actual state of volemia, with a close approximation by correlation analysis to the CVP index. Our study corroborates this idea. Our study shows a corelation between the maximum diameter of the IVC and the enlargment of the right cavities. This is not true of the IVC index.
It is important to highlight that the analysis of the IVC maintains its value of identifying the raised CVP values of these patients. This fact strikes us as important in that detecting incidences of hypovolemia is crucial for differential diagnoses or for preparing patients during weaning from ventilation. The presence of mechanical ventilation changes the respiratory physiology, altering the correlation of intrathoracic pressures. In the non-ventilated patient group, we saw that the IVC diameters were identical to those of the ventilated patients, but the IVC index was greater and the CVP lower (on average 20%). The degree of correlation between the CVP categorical variables and the IVC index was higher in the non-ventilated patients. To analyse these data, we have to bear in mind that many ventilated patients have concomitant cardiac alterations identified, in particular the patients with RV enlargement. Conversely, equally only 9 of these patients had CVP values lower than 7mmHg, meaning that the abovementioned rationale about the possibility of diagnosing typical low pressure situations in these patients with these methods (invasively and non-invasively) can be applied. The concomitant presence of mechanical ventilation and RV enlargement has not been explored, but it may reveal an association in which these data could be further heightened. The ventilated patients with worsening of chronic respiratory insufficiency could be particularly targeted. The Doppler data can be correlated with the various intravascular filling parameters. In our study, the mitral E/A relationship and the TRIV were not correlational parameters with the CVP. It should be stressed that these parameters are obtained at the level of the LV and the CVP is a filling parameter of the right ventricle. The practical use of these parameters can be questioned, as alterations in the cardiac rhythm and rate can change significantly or make their measurement invalid.

Clinical implications and conclusion
Using TTE to analyse the IVC (IVC index and maximum diameter) proves useful in the non-invasive evaluation of CVP in patients admitted to a PICU. The parameter which better correlated with the CVP was the ICV índex, especially in non-ventilated patients. We noted that a RV enlargement and in the patients admitted for worsening of chronic pulmonary disease, the correlations between the IVC index and the CVP were altered by the low CVP values. The existence of pathologies which impact on chronic overload of the right cavities can change the diagnostic viability of these methods in detecting incidences of hypovolemia. If in the PICU in which the study was carried out 63 (13.2%) patients had worsening of chronic pulmonary disease, there could be a much more significant rate of these patients and RV enlargement in ICUs for respiratory patients. Conversely, analysing IVC can identify states of major volemia in all the patients, including the patients with worsening of chronic pulmonary disease and RV enlargement, allowing in this way the detection of incidences of hypervolemia, important in critical situations such as ventilatory weaning.