Article, Pediatrics

Comparison of sonographic inferior vena cava and aorta indexes during fluid administered in children

a b s t r a c t

Objectives: This prospective, observational study evaluated changes in Ultrasound measurements of the inferior vena Caval index (IVCI), the aorta diameter/IVC diameter index (Ao/IVCD), and the aorta area/IVC area index (Ao/IVCA) during fluid administration in children requiring intravenous fluid administration.

Methods: Children who presented to the pediatric emergency department with symptoms of dehydration were enrolled between May 2015 and February 2016. The maximum diameter of the aorta, from inner wall to inner wall, and the long and short axis diameters of IVC were measured using a convex array transducer in the trans- verse view. Subsequently, we measured the diameter of the IVC at the subxiphoid area during inspiration and ex- piration in longitudinal view. We calculated IVCI, Ao/IVCD, and Ao/IVCA during administration of 10 ml/kg and 20 ml/kg normal saline boluses.

Results: IVCI and Ao/IVCA significantly changed immediately after administration of initial 10 ml/kg of NS. Ao/ IVCA showed significant change during the additional administration of 10 ml/kg (total 20 ml/kg) normal saline boluses (1.43, IQR 1.12-1.86 vs. 1.08, IQR 0.87-1.45, p value b 0.001). No significant changes were observed for IVCI and Ao/IVCD. Ao/IVCA was significantly correlated with the volume of fluid administered. The coefficient be- tween initial and administration of the 10 ml/kg normal saline bolus was -0.396 (p value = 0.010), and that be- tween the 10 ml/kg and 20 ml/kg normal saline boluses was -0.316 (p value = 0.038).

Conclusions: Ao/IVCA showed better correlations with the volume of fluid administered than IVCI and Ao/IVCA. Ao/IVCA might be a promising index for assessing the effects of fluid administration.

(C) 2018

Introduction

Accurate assessment of volume status in children remains one of the most challenging and important tasks for clinicians. Various individual clinical signs, symptoms, and laboratory markers such as body weight loss, capillary refill time, skin turgor, respiratory pattern, heart rate, urine output, serum bicarbonate help identify volume status in children [1]. However, none of these parameters are sufficient for accurately de- termining volume status and assessing the effects of fluid administra- tion [2].

Ultrasound techniques have been used for assessing volume status in children [3]. Several studies used inferior vena cava diameter, and aorta diameter ratio, rather than inferior vena caval index (IVCI) [4-7]. A new parameter, aorta/IVC cross-sectional area index (Ao/IVCA) was recently suggested, for predicting volume status because of limitations associated with the IVC-diameter measurement [8]. Ao/IVCA may better

* Corresponding author at: Department of Emergency Medicine, Seoul National University Bundang Hospital, 82, Gumiro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707, Republic of Korea.

E-mail address: [email protected] (H. Kwon).

predicts the need for Fluid replacement, compared to the aorta diame- ter/IVC diameter index (Ao/IVCD).

However, debate continues as to which index better reflects the fluid status and the effects of fluid administration of children. Our study aim was to evaluate and compare ultrasound parameters of the IVCI, Ao/IVCD, and Ao/IVCA during fluid administration in children requiring intravenous fluid administration.

Methods

Study design and setting

This prospective, observational study enrolled children who pre- sented to the PED between May 2015 and February 2016. This was a planned follow-up study which evaluated the accuracy of Ao/IVCA for detecting dehydration in children [8]. Ethical approval for the study was obtained from the Seoul National University Bundang Hospital In- stitutional Review Board (IRB No. B-1308/216-009). The study was con- ducted at an academic hospital located in a city with a population of 1,000,000 with N 24,000 visits to the PED each year.

https://doi.org/10.1016/j.ajem.2018.01.010

0735-6757/(C) 2018

Participant selection

All children under the age of 10-years, who presented to the PED with vomiting or diarrhea, and who need fluid administration were el- igible for inclusion. PED physicians determined the clinical dehydration scale and need for intravenous fluid replacement according to each child’s condition and dehydration-related symptoms [9]. Children re- ceived 10 ml/kg of normal saline intravenously (IV), every 30 min for 1 h. Exclusion criteria were congenital heart diseases, a clear alternative diagnosis rather than gastroenteritis at the triage unit, or life-threatening shock. The patients who did not require IV fluid administration were also excluded. The Research staff obtained written consents from participants’ parents/guardians.

Measurements & ultrasound protocol

Demographic data were obtained immediately after obtaining writ- ten consent. During clinical examination, the children were undressed, weighed to obtain a baseline weight, and examined. Each participant was placed in a supine position and one board-certified pediatric emer- gency physician, certified in critical care ultrasound, conducted ultra- sound measurement of the maximum aorta diameter and the long and short axis diameters of the elliptical IVC in the transverse position (probe marker facing to the participant’s right side) just inferior to the xiphoid process (Fig. 1a) in 5 min after IV fluid administration. The aorta and IVC were simultaneously visualized in cross section near the level of the entry of the hepatic veins. The investigator measured the maximum diameter of the aorta from inner wall to inner wall, and mea- sured the long and short axis diameters of IVC. IVC cross-sectional area was calculated as 3.14 x 1/2 of the long axis diameter x 1/2 of the short axis diameter and the aortic cross-sectional area was calculated as 3.14

x (1/2 of the diameter)2. Subsequently, longitudinal sonographic views

of IVC were obtained and the diameter of IVC, just below hepatic vein, and its changes were measured during respiration (Fig. 1b). IVCI was calculated as:

Maximal diameter (expiratory) of IVC-minimal diameter (inspiratory)

of IVC/maximal diameter (expiratory) of IVC

These ultrasound measurements were conducted immediately after administering the 10 ml/kg and 20 ml/kg NS boluses. We used a 4C-RS with a frequency range of 1.6-4.6 MHz convex array transducer (Vivid S5, General Electronics) at bedside.

Sample size

The required sample size of 34 was calculated based on previous study [8], using the assumption that the expected mean of Ao/IVCA was

1.61 with standard deviation (SD) of 0.1 and the change of Ao/IVCA would be 0.1 upon administration of 10 ml/kg NS, without change in SD.

Outcomes

The primary outcome was to compare initial values and changes in IVCI, Ao/IVCD, and Ao/IVCA during administration of 10 ml/kg and 20 ml/kg NS boluses. The secondary outcome was to evaluate the reli- ability of IVCI, Ao/IVCD, and Ao/IVCA relative to the volume of the ad- ministered bolus.

Statistical analysis

The STATA 14.2 software (Stata Corp LP, College Station, Texas, USA) was used for statistical analyses. Data were expressed as the median and interquartile range (IQR). Fisher’s exact test was used for categorical data and Dunn’s test was used to estimate the differ- ences between two or more groups if the data were non-parametric. The value of the dependent variable for each 10 ml/kg bolus admin- istered was calculated and the median value and interquartile range were reported. To express the correlation between variables, we assessed linear regression for parametric variables. We determined the utility of each method by comparing the regression coefficient of IVCI, Ao/IVCD, and Ao/IVCA, according to administration of every 10 ml/kg of NS. Probability (p) values b 0.05 were considered statistically significant.

Results

Participant characteristics

Thirty-four children were enrolled (Table 1) and all participants were diagnosed with gastroenteritis. The sex ratio was equal and diar- rhea was the most common chief complaint.

Primary outcome

IVCI and Ao/IVCA changed significantly after administration of 10 ml/kg of NS. Between 10 ml/kg and 20 ml/kg administration of NS, no change was observed in IVCI and Ao/IVCD, but Ao/IVCA changed

Fig. 1. Ultrasound measurement of aorta and inferior vena cava. (a) Measurement of aorta/inferior vena cava diameter and area index. The aorta maximum diameter and the long and short axis diameters of elliptical IVC were measured in the transverse position just inferior to the xiphoid process. The aorta and IVC were simultaneously visualized in cross section near the level of hepatic veins entry. (b) Measurement of inferior vena caval index. Longitudinal sonographic views of the IVC were obtained and the diameter of IVC, just below hepatic vein, and its changes were measured during respiration.

Table 1

Participant characteristics.

Sex

Male, n (%) 17 (50)

Female, n (%) 17 (50)

Age (month), median (IQR)

Weight (kg), median (IQR) 14 (11.5-18)

Clinical dehydration scale, median (IQR) 5 (3-7) Chief complaint, total n = 34

Vomiting, n (%) 12 (34)

Diarrhea, n (%) 13 (38)

Fever, n (%) 6 (18)

Lethargy, n (%) 3 (10)

pH, median (IQR) 7.395 (7.36-7.43)

Bicarbonate(mmol/l), median (IQR) 22.5 (22-24) CI, confidence interval; IQR, interquartile range.

significantly (1.87, IQR 1.41-2.42 vs. 1.43, IQR 1.12-1.86 vs. 1.08, IQR

0.87-1.45, p value b 0.001) (Table 2). In the IVCI, two indexes increased after administering a 10 ml/kg NS bolus; other indexes concavely de- creased after fluid administration (Fig. 2a). Eleven indexes convexly de- creased in Ao/IVCD (Fig. 2c).

Secondary outcome

We compared differences in index coefficients during bolus admin- istration to determine index reliability (Table 3). Ao/IVCA demonstrated a significant correlation between indexes. The correlation coefficient between no fluid administration of a 10 ml/kg NS bolus was -0.396 (p value = 0.010), and the correlation coefficient between 10 ml/kg and 20 ml/kg administration was -0.316 (p value = 0.038). Ao/IVCA appears more feasible for evaluating the effectiveness of fluid adminis- tration, compared to IVCI and Ao/IVCD.

Discussion

To the best of our knowledge, this study is the first to compare changes in IVCI, Ao/IVCD, and Ao/IVCA that result from fluid administra- tion. The results of this study showed that Ao/IVCA in children was closely correlated with measurable (on ultrasound) changes resulting from administration of both 10 ml/kg and 20 ml/kg NS boluses. IVCI and Ao/IVCD were less reflective of volumetric changes from fluid administration.

Point-of-care ultrasound is useful diagnostic tool in pediatric pa- tients because of its relative safety, cost-effectiveness, portability, versa- tility, and ease of use [10]. In addition to its many other uses, ultrasound can assess volume status in children and adults; however, a recent sys- tematic review found insufficient evidence to justify the use of ultra- sound for diagnosing dehydration in children, however the study cohort was small in this investigation [3]. Other recent studies identified specific ultrasound methods for identifying dehydration and body fluid status in children [5-8,11-14]. These methods consist of measuring the diameter of the IVC and abdominal aorta. Aortic diameter varies relative

to age, sex and body surface, but does not vary relative to the level of hy- dration, and the inferior vena cava and aorta develop at similar time points during fetal development [15]. Until now, no research has used ultrasound to determine changes in body fluids in children.

IVCI reflects body fluid volumes, which are calculated based on the

measurement of the diameter of the vein in two states – the inspiratory phase and the expiratory phase [16]. Unlike the resilient aortic wall, the wall of IVC changes shape during respiration. During inspiration, the dome of the diaphragm lowers, and intrathoracic pressure decreases. As a result, the wall of the IVC collapses. Expiration involves the oppo- site – the diaphragm relaxes, intrathoracic pressure increases, the wall of the inferior vena cava returns to its original shape and its dimension becomes larger.

However, the cross-sectional shape of the IVC appears elliptical on ultrasound images taken with the probe placed just inferior to the xi- phoid process. The measurement of anteroposterior diameter in the longitudinal sonographic view is not same as the short or long diameter in the transverse sonographic view of the IVC. The measurement of the maximum diameter is equal to measuring the long axis diameter of the elliptical cross-sectional area of the IVC, but the short axis diameter is more sensitive to preloading and pressure than the long axis diameter. Even in this study, two indexes of IVCI increased after administration of a 10 ml/kg NS bolus and eleven indexes of Ao/IVCD decreased convexly. However, a priori, all indexes should decrease concavely; however, we did not observe this. For these reasons, we investigated a new method for overcoming these limitations and introduced cross- sectional area measures, rather than the maximal diameter of IVC mea- sures, for fluid status, during fluid administration.

The accurate assessment of fluid status and decision-making re-

garding methods of rehydration (oral or intravenous fluid therapy) in children are challenging because of the unreliability of initial clin- ical signs and symptoms [17,18]. Ao/IVCA provides relatively accu- rate measurement of fluid status in children [8]. However, no recent studies use ultrasound to predict changes in fluid volumetrics in children. No previous studies combined clinical presentation and Ao/IVCA for evaluating fluid responsiveness, but our results showed that Ao/IVCA significantly correlated with fluid administration. Fur- ther research is needed to examine Ao/IVCA in combination with other objective clinical features and Laboratory markers for evalua- tion of fluid responsiveness.

This study had several limitations. The most obvious was that ultra- sound measurements were performed by only one experienced pediat- ric emergency physician, certified in critical care. This might influence the robustness of the study and interrater reliability, but we tried to show in an unbiased manner that Ao/IVCA was better correlated with fluid administration than IVCI and Ao/IVCD. Second, children over the age of 10 years were not enrolled because this was a planned secondary analysis conducted using data from another study that evaluated the ac- curacy of Ao/IVCA for detecting dehydration and the need for fluid ad- ministration. Third, we could not assess the response of the indexes, during fluid administration, relative to the degree of dehydration. The number of participants was insufficient to assess the correlation between the degree of dehydration and the ultrasound findings.

Table 2

Comparing IVCI, Ao/IVCD, and Ao/IVCA during administration of 10 ml/kg and 20 ml/kg NS boluses.

Fluid administration

IVCI

Ao/IVCD

Ao/IVCA

Median (IQR)

p valuea

Median (IQR)

p valuea

Median (IQR)

p valuea

No fluid

0.59 (0.48-0.65)

0.0026

0.96 (0.76-1.07)

0.0533

1.87 (1.41-2.42)

0.0204

10 ml/kg

0.48 (0.42-0.56)

0.0473

0.89 (0.74-1)

0.0407

1.43 (1.12-1.86)

0.0207

20 ml/kg

0.45 (0.4-0.48)

0.80 (0.67-0.9)

1.08 (0.87-1.45)

Underlined values are statistically significant.

Ao/IVCD: aorta-inferior vena cava diameter index, Ao/IVCA: aorta-inferior vena cava area index, IVCI: inferior vena cava index, IQR: inter-quartile range, NS: normal saline.

a In Dunn’s test, ? is 0.05 and p value is one-sided.

Fig. 2. Comparing of inferior vena caval index (IVCI), aorta/inferior vena cava diameter index (Ao/IVCD), and aorta/inferior vena cava area index (Ao/IVCA) according to fluid administration. (a, b) IVCI and its predicted value, (c, d) Ao/IVCD and its predicted value, (e, f) Ao/IVCA and its predicted value.

Fourth, this study demonstrated changes in sonographic indexes after fluid administration, not fluid responsiveness. Further study (currently ongoing) is needed to evaluate volumetric fluid changes in children during rehydration therapy. Finally, this was a single cen- ter study, and we therefore did not assess feasibility and repeatability.

In conclusion, this study showed that Ao/IVCA may help determine the effects of fluid administration in children. Ao/IVCA may help

healthcare professionals diagnose fluid status in children, initiate appro- priate therapy, and provide effective treatment to prevent mortality and morbidity.

Funding

No external funding for this manuscript.

Table 3

Correlation between administration of NS and IVCI, Ao/IVCD, and Ao/IVCA.

NS

Coefficient

Standard error

p value

95% CI

IVCI

0-10 ml/kg

-0.084

0.024

b0.001

-0.132 to -0.035

10-20 ml/kg

-0.044

0.076

b0.001

-0.092-0.005

Ao/IVCI

0-10 ml/kg

-0.076

0.045

0.097

-0.166-0.014

10-20 ml/kg

-0.074

0.108

0.10

-0.163-0.163

Ao/IVCA

0-10 ml/kg

-0.396

0.150

0.010

-0.694 to -0.098

10-20 ml/kg

-0.316

0.038

0.038

-0.614 to -0.018

Ao/IVCD: aorta/inferior vena cava diameter index, Ao/IVCD: aorta/inferior vena cava area index, CI: confidence interval, IVCI: inferior vena caval index, NS: normal saline.

Disclosure

The authors declare no conflict of interest.

Authors’ contributions

All authors participated in the design of study, Data interpretation.

H.K. and Y.A.C. are responsible of participant recruitment, data collec- tion. Y.A.C. is the principle responsible of data interpretation, analyses, and manuscript preparation. H.K., J.H.L., J.Y.J., Y.J.C. and Y.A.C. were in- volved critical revision of manuscript. All authors read and approved the final manuscript.

Acknowledgements

We would like to acknowledge the contributions of Medical Re- search Collaborating Center of Seoul National University Bundang Hos- pital for their important contributions to data collection and the management of the dataset.

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