Estimation of Central Venous Pressure Using Cardiac Ultrasound of Inferior Vena Cava in Ventilated Children: A Prospective Multicenter Observational Study

doi:10.21203/rs.3.rs-5238832/v1

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Estimation of Central Venous Pressure Using Cardiac Ultrasound of Inferior Vena Cava in Ventilated Children: A Prospective Multicenter Observational Study

https://doi.org/10.21203/rs.3.rs-5238832/v1

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Background:
Although ultrasound (US) parameters of the inferior vena cava (IVC) cannot be used to estimate central venous pressure (CVP) in adults under mechanical ventilation (MV), the limited pediatric literature reports highly contradictory results. Pediatric evidence was awaited.

Methods:
This prospective, multicenter, observational study, conducted in six pediatric intensive care units, included children aged 2 days to 12 years who were under MV and had a central venous catheter in the superior vena cava to monitor CVP. US measurements were performed by experienced intensivists in order to calculate the following parameters: i) IVC-Collapsibility: [(IVCdmax - IVCdmin)/IVCdmax] x 100, ii) IVC-Distensibility: [(IVCdmax - IVCdmin)/IVCdmin] x 100, iii) IVC/Aortic: (IVCdmax/Ao) x 100. The search for correlation was studied using scatter plot and Pearson and Spearman's correlation tests for linear and monotonic relationships, respectively.

Results:
We included 120 children with a median age of 11.5 [2.0; 46.3] months and a median weight of 9.0 [5.0 ;15.0] kg. A third of the patients were admitted for post-operative care, including cardiac surgery, and a fourth for respiratory failure, with a median CVP of 7.5 [5.0; 10.3] mmHg at inclusion. No significant relationship was found between CVP and IVC-Collapsibility (Pearson r = -0.05, p = 0.55; Spearman r = -0.09, p = 0.32), IVC/Ao (Pearson r = 0.16, p = 0.08; Spearman r = 0.17, p = 0.06), or IVC-Distensibility (Pearson r = -0.003, p = 0.97; Spearman r = -0.09, p = 0.29).

Conclusion:
There is no correlation between CVP and IVC-US parameters in children under MV.

Echocardiography

Collapsibility Index

Distensibility Index

Central Venous Catheter

Paediatric Intensive Care Unit

Mechanical Ventilation

Right Atrial Pressure

Central venous pressure (CVP) remains a vital tool for managing severe patients in pediatric intensive care units (PICUs), particularly those with hemodynamic instability [1, 2], head trauma [3], or those requiring perioperative care following cardiac surgery [4]. The gold standard for CVP measurement is the invasive method, which involves placing a central venous catheter (CVC) at the junction of the right atrium (RA) and superior vena cava (SVC) [1]. In the absence of a SVC-CVC, CVP can be estimated using ultrasound (US) measurements of the inferior vena cava (IVC) in spontaneous breathing (SB) patients [5]. In mechanically ventilated (MV) adults, these indices are unreliable for estimating CVP [6]. However, the limited pediatric literature provides highly contradictory findings [7–12]. To address this gap, we have designed a prospective multicenter study aimed at demonstrating the clinical relevance of estimating CVP through IVC US measurements in MV children.

This prospective, multicenter, observational study was conducted between November 1, 2021, and June 30, 2023 across six PICUs in France following approval by the ethics assessment committee of Robert-Debre University Hospital.

Patients

We included children admitted to one of the six PICUs, aged from 2 days post-term to 12 years, who were under MV and had a SVC-CVC in place. To demonstrate a moderate correlation (r = 0.40) between the studied variables, with a two-tailed α of 0.05 and a power of 0.90, 62 subjects were required. Accounting for an estimated 3% risk of invalid data and planning for subgroup analysis based on potential age-related variability, we aimed to recruit 120 patients [13]. Exclusion criteria included non-echogenic patients, those with unrepaired ventricular or atrial septal defects, patients with moderate to severe pulmonary or tricuspid valve regurgitation, and those with an open chest following cardiac surgery.

Data collection and methodsDemographic (age, sex, weight) and medical data, on admission to PICU and at the time of inclusion, including the reason for hospitalization, severity score, ventilatory parameters, and inotrope use were collected for each patient. Good positioning of the tip of the SVC-CVC in order to make CVP measurements was assessed by radiography or US [1]. After leveling the pressure transducer to the RA, the measurement was obtained on the monitor, ensuring the absence of extrasystole or spontaneous breathing (SB) that could distort the waveform [14]. For this study, US was only performed by experienced physicians from each participating PICU, all of whom had completed a minimum of 40 pediatric echocardiograms, in accordance with recent guidelines [5]. Notably, 114 out of 120 US measurements (95%) were captured in B mode to minimize axis-related measurement errors [15]. Each US measurement was repeated three times. The mean of the three values was recorded.

Ultrasound parameters

The US indices were calculated by the principal investigator (PS) using the following formula:

IVC-Collapsibility (IVC-CI): [(IVCdmax - IVCdmin)/IVCdmax] x 100, [5]

IVC/Aortic (IVC/Ao): (IVCdmax/Ao) x 100, [11]

IVC-Distensibility (IVC-DI): [(IVCdmax - IVCdmin)/IVCdmin] x 100, [16]

Statistics

To describe the population, qualitative variables are presented as frequencies (percentages), and continu variables are presented as medians [first quartile - third quartile]. The correlation between CVP and US parameters was first studied using a graphic representation (scatter plot) on the whole population. Linear relationships were studied with Pearson correlation test (r) and monotonic relationships with Spearman's correlation test (ρ). The tests were carried out after verification of their conditions of application. The coefficients resulting from the tests range from − 1 to + 1. Those tests were repeated on subgroups of the population according to age ([ 2 days-2 years [, [ 2 years, 12 years [). P-values less than 0.05 was considered as significant. The statistical analysis was carried out using RStudio^® version 4.0.3 (RStudio, PBC, Boston, MA, USA) and the Jamovi 1.2^® graphical interface (The Jamovi project, Sydney, Australia).

A total of 120 patients were included, and their main clinical characteristics are reported below (Table 1).

Table 1

Patients characteristics on admission to PICU and at CVP and IVC US parameters measurements.
	n = 120
Demographics
Age (months) Age < 2 years (%) Sex (male) Weight (Kg)	11.5 [2.0 ;46.3] 76 (63.0%) 58 (48.3%) 9.0 [5.0 ;15.0]
Reason for hospitalization ^*
Postoperative	43 (35.8%)
Respiratory failure	28 (23.3%)
Hemodynamic failure	22 (18.3%)
Neurological failure	14 (11.7%)
Cardiorespiratory arrest	5 (4.2%)
Digestive failure	3 (2.5%)
Metabolic failure	3 (2.5%)
PREDICTED MORTALITY on admission
PIM-3 (%) ^£	2.3 [1.0 ; 7.8]
Ventilatory parameters
Volume Assisted Controlled Ventilation	96 (80.0%)
Mean Airway Pressure (cmH₂O) ^$	11.0 [9.0 ;13.0]
PEEP (cmH₂O)	6.0 [5.0 ;7.0]
Treatment with inotropes	38 (31.6%)
CVP (mmHg)	7.5 [5.0 ; 10.3]
Ultrasound measurements
Maximum IVC diameter (mm)	7.2 [5.3 ; 10.3]
Minimum IVC diameter (mm)	6.2 [3.9 ; 8.5]
Maximum aorta diameter (mm)	6.7 [5.4 ; 8.4]

PIM-3: Pediatric Index of Mortality-3 ; PEEP: Positive end-expiratory pressure ; PICU: Pediatric Intensive Care Unit ; CVP : Central Venous Pressure ; IVC: Inferior Vena Cava ; Data are reported as medians [first quartile - third quartile], and N (%). (Missing data: *: n = 2 ; £: n = 10 ; $: n = 3).

Graphical analysis using a scatterplot (Fig. 1A) did not show a visual relationship between IVC-CI and CVP values, nor did the statistical analysis, which revealed no significant association (r = -0.05, p = 0.55; ρ = -0.09, p = 0.32). Similar results were found for IVC-DI (r = -0.003, p = 0.97; ρ = -0.09, p = 0.29) (Fig. 1B). For the IVC/Ao ratio, we observed a slight positive trend in the coefficient, but no significant statistical association (r = 0.16, p = 0.08; ρ = 0.17, p = 0.06) (Fig. 1C).The linear correlation between the various US parameters and CVP for patients aged between 2 days and 2 years (n = 76) was not statistically significant: IVC-DI (r = -0.14, p = 0.22; ρ = -0.17, p = 0.13); IVC-CI (r = -0.19, p = 0.1; ρ = -0.20, p = 0.40); and IVC/Ao (r = 0.16, p = 0.17; ρ = 0.19, p = 0.09). Similar results were found in the subgroup of patients aged 2 to 12 years (n = 44): IVC-DI (r = 0.24, p = 0.12; ρ = 0, p = 0.97); IVC-CI (r = 0.18, p = 0.24; ρ = 0.24, p = 0.96); and IVC/Ao (r = 0.14, p = 0.35; ρ = 0.18, p = 0.23).

US parameters based on variations in the IVC diameter were unsuccessful in estimating CVP in MV children aged 2 days to 12 years.

CVP is a crucial hemodynamic parameter in several cases within PICUs [1–4], and typically requires invasive measurement via a SVC-CVC [1]. Similar to adults [5, 17], CVP in SB children can also be assessed using US measurements of IVC diameter variations [18]. However, while it is well-established that CVP cannot be accurately estimated by US measurements of the IVC in MV adults [5, 6], the relevance of these findings for MV children in the PICU remained debated. To date, only six single-center studies have explored this issue [7–12], often combining data from SB and MV children or using varying CVP measurement techniques that deviate from international guidelines, leading to inconsistent results. Therefore, validating the accuracy of CVP evaluation via IVC US measurements in a large cohort of MV children was essential for pediatric intensivists.

This first prospective multicenter study has several notable strengths. This is the only study to date that has included such a large cohort of 120 exclusively MV children, whose general characteristics closely resemble those of the pediatric population usually admitted to the PICU [19]. Our CVP measurement protocol adhered strictly to the guidelines set by the European Society of Pediatric and Neonatal Intensive Care [1], employing a CVC placed at the junction of the RA and the SVC. Finally, in our study, all US measurements were performed by experienced pediatric intensivists at each participating PICU who strictly adhered to a standardized protocol, thereby minimizing the risk of error.

Our results are in accordance with those previously reported by Basu et al. in a single-center study involving 50 MV children [9] which noted the lack of correlation between CVP and IVC US measurements. In contrast, other studies have often analyzed mixed populations of SB and MV children [7, 8, 10–12], making their data difficult to interpret. Furthermore, in the studies that included MV children, the level of positive end-expiratory pressure (PEEP) was reported in only two out of six studies [7, 11]. Only one other single-center pediatric study, involving 15 children, systematically used an SVC-CVC for hemodynamic profiling with a Pulse Index Contour Cardiac Output device [10]. The results of this study are difficult to interpret due to repeated measurements in both SB and MV children. Additionally, Basu et al. noted that only two-thirds of the children had CVP measurements using an SVC-CVC [9].

Despite the strict protocols for CVP and US data acquisition, our study, conducted under real-world conditions at the bedside of MV children in six PICUs, may have been biased by the exclusion of patients with extreme CVP values due to the urgent need for critical management, such as in cases of severe hypovolemic shock with very low CVP or extreme congestive heart failure with high RA pressure. Notably, one-third of the included patients had CVP values either below 4 mmHg (n = 17) or above 12 mmHg (n = 17). Another potential limitation is the reduced statistical power (P = 0.77) in our subgroup of patients older than two years (n = 44). While these findings should be generalized with caution, it is important to highlight that no previous study has reported such a large cohort of MV patients in this age group with CVP measurements conducted strictly according to the guidelines [1]. All these factors collectively enhance the external validity of our results.

In conclusion, this prospective multicenter study found no significant correlation between CVP and IVC US measurements in MV children aged 2 days to 12 years of age. These findings suggest that IVC US measurements should not be relied upon for precise CVP estimation in this population. However, the effectiveness of the semiquantitative method based on the visual assessment of the IVC without detailed calculations [17] still needs to be rigorously evaluated in the PICU.

Aortic diameter

CVP

Central Venous Pressure

CVC

Central Venous Catheter

IVC

Inferior Vena Cava

IVC-CI

Inferior Vena Cava - Collapsibility Index

IVC-DI

Inferior Vena Cava - Distensibility Index

IVC/AO

Ratio between the maximum diameter of the Inferior Vena Cava and the Abdominal Aorta

Mechanical Ventilation

PEEP

Positive End-Expiratory Pressure

PICU

Pediatric Intensive Care Unit

Right Atrium

Spontaneous Breathing

SVC

Superior Vena Cava

Ultrasound

Ethic approval and consent to participate: The study was approved by the ethics review committee for research projects at Robert Debré Hospital, Paris (#00006477).

Consent for publication : All families were informed of the use of their data for research and had the right to refuse it.

Availability of data and materials : The datasets generated and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests : The authors declare that they have no competing interests.

Funding : This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Author’s contributions :

PS and SD have made substantial contributions to the conception and study design.

PS, AH, AG, CC, CM, SDe, RK, JR, OB and SD have made substantial contributions to the acquisition of data.

PS, EL, OB and SD have analysed and interpretated the data.

PS have drafted the work and OB and SD have revised it.

All authors have approved the submitted version and have agree to be personally accountable for the author’s own contributions and to ensure that questions related to the accuracy or integrity of any part of the word, even ones in which the author was not personally involved, are appropriately investigated, resolved, and the resolution documented in the literature.

Acknowledgements: We would like to thank the medical and paramedical teams of the various PICUs that took part in the study for their involvement. We would also like to thank the patients and their families for agreeing to take part in this study. Finally we sincerely thank Dr Michael Levy for his carefull reading of our manuscript and his unvaluable suggestions.

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No competing interests reported.

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Estimation of Central Venous Pressure Using Cardiac Ultrasound of Inferior Vena Cava in Ventilated Children: A Prospective Multicenter Observational Study

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Version 1

Abstract

Figures

INTRODUCTION

METHODS

Patients

Ultrasound parameters

Statistics

RESULTS

DISCUSSION

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1