In their everyday work pediatricians and neonatologists nearly always assess the body fluid status of small patients during physical examination (for example, routine examination of the throat includes the evaluation of oral mucosa moisture level). The majority of pediatric conditions (upper respiratory tract infections, gastroenteritis, pyrexia) cause a change in body fluid status, usually dehydration. The evaluation of fluid status determines further management of the disease, i.e. the decision on the method of treatment (possible hospitalization) and hydration measures (oral or intravenous route). Unfortunately, no ideal diagnostic tool that could meet the expectations of clinicians has been found to date(1, 2).
Material and method
In 2013 fifty neonates were examined. The authors based their study on the paper “Usefulness of ultrasound examination in evaluation of body fluid status”(1). The aim of the study was to establish reference values for this age group. The study was conducted in two hospitals in the Lower Silesia region of Poland and included two groups: 25 healthy newborns from the Department of Neonatal Physiology and Pathology with an Intensive Care Sub-Unit of the Regional Specialist Hospital “Latawiec” in the city of Świdnica and 25 sick newborns from the Department of Neonatal and Infant Pathology of Dr. Alfred Sokołowski Specialist Hospital in Wałbrzych, Poland. The group of healthy neonates included full-term newborns with no perinatal complications and with a mean birth weight of 3425 g. The group of sick neonates included newborns with heart defects in the form of ostium secundum atrial septal defect (ASD II), ventricular septal defect (VSD), permanent foramen ovale (PFO) and patent ductus arteriosus (PDA) as well as newborns with complications that occurred during the first days or weeks of life in the form of neonatal jaundice or pneumonia. Mean birth weight in this group was 3067 g.
Before the study consent for ultrasound examination was obtained from the patients’ parents and from the heads of both neonatal units. The following ultrasound devices were used:
in Świdnica – Siemens Acuson X300 P 8–4 MHz, Korea 2012;
in Wałbrzych – Philips HD15 C 8–5 MHz, USA 2012.
The measurements of the inferior vena cava (IVC) were conducted according to the method described in the work cited above – in the intrahepatic section below the confluence of hepatic veins, where the anterior and posterior walls of IVC run parallel to each other(1). The ultrasound probe was placed in the substernal area in the longitudinal plane in M-mode in the breathing phase and the largest (expiration) and the smallest (inspiration) dimensions of the vein (its two diameters) were measured (Fig. 1).
Measurement of the inferior vena cava diameter during the inspiratory and expiratory phase
The diameter of the abdominal aorta (aorta abdominalis, AAB) was measured 5–10 mm above the origin of the celiac trunk with the probe placed in the substernal area in the transverse plane (Fig. 2).
Measurement of the abdominal aorta diameter
Subsequently three parameters were calculated for each patient. The IVC/AAB index was divided into two indices: IVC1/AAB and IVC2/AAB, where IVC1 was the diameter of the inferior vena cava in the expiratory phase and IVC2 was the diameter in the inspiratory phase. The third parameter – inferior vena cava collapsibility index (CI) was calculated as the ratio of the difference in the diameter of the inferior vena cava measured during expiration and inspiration (IVC1–IVC2) to the diameter of the vein during expiration (IVC1).
Statistical calculations were conducted on a group of 50 patients (25 sick patients – the study group, 25 healthy patients – the control group). The results with p < 0.05 were considered statistically significant. Statistical analysis was carried out using the StatSoft, Inc. (2011) STATISTICA version 10 package.
The normality of the data distribution was checked using the Shapiro-Wilk test. The distribution of CI values in the group of healthy patients was consistent with a normal distribution, while in the group of sick patients it deviated from it. Therefore, the non-parametric Mann-Whitney U test was used. Medians with quartiles as well as minimum and maximum values are presented on the diagram. The distribution of the IVC1/AAB and IVC2/AAB values in the groups of healthy and sick patients met the conditions of a normal distribution. Therefore, the parametric Student t-test was applied. Mean values, standard error, outliers and extreme values are presented on the diagram.
In the population under analysis the difference between CI in healthy neonates and CI in sick neonates is statistically significant: p = 0.001 (Fig. 3). Mean CI value in the studied healthy newborns is 0.28 (standard deviation: 0.13). In the group of sick neonates, on the other hand, CI is 0.16 (standard deviation: 0.13). The range of values between the 10th and 90th percentile in the group of healthy newborns is considered to be the reference range: 0.12–0.46 (Fig. 4).
Box plot: whiskers for the groups of healthy and sick neonates for CI values
Histogram for the group of healthy neonates for CI values
Another index calculated in the study is the ratio of the inferior vena cava diameter during the expiratory phase to the diameter of the aorta (IVC1/AAB). Statistical analysis revealed that this index is not significantly different (p = 0.393 – statistically insignificant difference) between the groups of sick and healthy children. Higher values are observed in sick neonates (Fig. 5). In the group of healthy newborns the mean IVC1/AAB value is 0.73 (standard deviation 0.17) and in the group of sick neonates the figures are 0.79 and 0.22, respectively. The analysis allows for establishing the following norm determined by the 10th and 90th percentile for the group of healthy neonates: 0.51–0.96 (Fig. 6).
Box plot: Whiskers for the groups of healthy and sick neonates for IVC1/AAB values
Histogram for the group of healthy neonates for IVC1/AAB values
Finally, the ratio of the inferior vena cava diameter during the inspiratory phase to the diameter of the aorta (IVC2/ AAB) was calculated. The difference between the two study groups is statistically significant: p = 0.018 (Fig. 7). In the group of healthy newborns the mean IVC2/AAB value is 0.53 (standard deviation 0.17) and in the group of sick neonates the figures are 0.67 and 0.23, respectively. The values of extreme percentiles for the healthy neonates are: 0.34–0.77 (Fig. 8).
Box plot: Whiskers for the groups of healthy and sick neonates for IVC2/AAB values
Histogram for the group of healthy neonates for IVC2/AAB values
Fluid balance disorders in neonates
Children, including newborns, are particularly sensitive to fluctuations in the fluid volume in the body associated with various disease processes. The total body water (TBW) is divided into extracellular fluid (ECF), which accounts for 1/3 of the TBW and intracellular fluid (ICF), which accounts for 2/3 of the TBW. The ECF space includes a few compartments such as plasma volume, interstitial fluid (it surrounds all cells except for blood cells and includes lymph) and transcellular fluid (fluid located in the lumen of epithelium-covered structures; it includes gastrointestinal tract secretions, perspiration, cerebrospinal, pleural, pericardial, peritoneal and synovial fluid, aqueous humour of the eyes, bile as well as intestinal, thyroid and cochlear fluid). The daily fluid exchange in a neonate is as high as 25% of the TBW, while in an adult individual this proportion is close to 6%(3). It should be noted that in adults the extracellular fluid accounts for 33% of the total body water while in newborns this proportion is 53%. As a result, the clinical picture of dehydration in neonates is more spectacular. Increased water demand is caused by diarrhea, vomiting, respiratory tract infections with accompanying fever, tachypnea, diseases with polyuria (diabetes mellitus, diabetes insipidus), light therapy, the use of open incubators, the use of a tracheostomy, a nasogastric tube, surgical drains as well as burn treatment. Decreased water demand is found in hypothyroidism, diseases with accompanying oliguria or anuria (renal insufficiency, syndrome of inappropriate antidiuretic hormone secretion [SIADH]) and when humidifiers are used in ventilators(4).
Methods of hydration assessment
A dehydrated newborn always looks sick. The child may sometimes have a reduced level of consciousness, which, however, is difficult to assess since it sleeps almost all day. Mild dehydration may only manifest itself with increased thirst. A common symptom of dehydration is dry oral mucosa, although it may also occur in other pathological conditions (e.g. in acidosis). Another symptom which suggests dehydration is decreased elasticity of tissues on the abdomen, chest and thigh (although the assessment of the skin and muscle fold exclusively on the abdomen may be misleading, since the abdomen is often distended). Sunken eyes, lack of tears during crying and depressed anterior fontanelle are also clinical signs of dehydration; however, they do not seem to be fully reliable. Also, the child's body mass may be measured every day and the volume of passed urine may be observed, but these methods are timeconsuming. With a growing water deficit signs of circulatory failure also occur, such as peripheral vasoconstriction (the skin becomes cold and marble-like) and a slow refill of cutaneous capillary bed following pressure on the earlobe and nail plate – the capillary refill time becomes longer. These signs, however, may also be affected by the ambient temperature, therefore, they must be interpreted with caution. Severe dehydration is accompanied by shock and tachycardia, low tension, thready pulse and low arterial pressure. Fluid deficit of 50 ml/kg causes tachycardia, which occurs during an infection or fever(3).
Laboratory tests may help assess body fluid status. For example, significant dehydration causes urine specific gravity to be elevated and once fluids are replenished, it decreases. Urinalysis in dehydrated patients shows the presence of hyaline and granular casts, single white and red blood cells as well as proteinuria at the level of 30–100 mg/dL. Blood count reveals elevated hemoglobin and hematocrit levels (although in patients with anemia these parameters may be within reference ranges). Protein concentration assay is of doubtful utility, especially in hypotrophic neonates. Creatinine and urea levels increase in dehydrated neonates; however, these parameters are not useful for the assessment of body fluid status in patients with renal insufficiency. Another method involves determination of plasma electrolyte levels combined with ECG examination (hyperand hypokalemia)(4). Echocardiography may also be used, but it requires a high level of experience from the examiner as well as specialist equipment.
Sonography in the evaluation of body fluid status
According to reports by doctors from the Medical University of Gdańsk of 2006(1) ultrasound examination may be useful for the assessment of body fluid status in the pediatric population as well. This method consists in the measurement of the diameter of the inferior vena cava and abdominal aorta. The aorta was chosen for two reasons. Firstly, its diameter depends on the age, sex and body surface, but does not depend on the level of hydration. Secondly, the inferior vena cava and aorta develop at the same time during fetal life(5, 6). The results of this study were presented at the 18th European ultrasound meeting Euroson 2006 in Bologna, Italy(1). The study was subsequently printed in the American Journal of Emergency Medicine(7). Another element presented in this study is inferior vena cava collapsibility index, which is calculated based on the measurement of the diameter of the vein in two states – the inspiratory phase and the expiratory phase(1). Unlike the resilient aortic wall, the wall of the vein changes shape during respiration. During inhalation the dome of the diaphragm is lowered (flattens), which causes chest volume to expand. As a result of these changes abdominal pressure increases and the wall of the inferior vena cava becomes compressed (collapses), thus creating the smaller dimension of the vessel. Exhalation involves the opposite – the diaphragm relaxes, abdominal pressure decreases, the wall of the inferior vena cava returns to its original shape and its dimension becomes larger. In the past Cheriex established a normal range for the diameter of the vein in relation to body surface. He also determined a reference value range for the inferior vena cava collapsibility index for the adult population of 0.4–0.75(1, 8). Natori also studied body fluid status assessment using ultrasound in 1979 r. He observed a relationship between the change of the inferior vena cava diameter and pressure in the right atrium of the heart(1, 9). In 2007 a study was published in the Academic Emergency Medicine on a pediatric population in which the usefulness of the aorta/inferior vena cava index was evaluated(10). In November 2014 another paper concerning this issue was published. In this work the results of measurements of hydration performed by experienced and inexperienced examiners were assessed. The paper shows that the measurement of the inferior vena cava/aorta index is a quick test that is easy to master for individuals who do not have a particularly large experience in working with the ultrasound device(11). In 2014 in the Critical Ultrasound Journal a paper was published in which the authors demonstrated that the inferior vena cava/aorta index was not a very reliable indicator of significant dehydration in children; in addition, the inferior vena cava collapsibility index and physical examination were not helpful in the assessment of body fluid status in this age group(12).
There is no single, perfect method of the assessment of body fluid status in neonates. Many different symptoms and parameters should be taken into account. Therefore, it seems especially justified to use imaging to this end in the form of ultrasound assessment of the inferior vena cava. The use of ultrasound for the measurement of the inferior vena cava diameter seems to be a very good method for the youngest of patients – neonates, including preterm newborns. Even though the usefulness of this examination has already been proven many times, it has not widely entered everyday clinical practice yet. It seems that further prospective studies are needed to evaluate the usefulness of diagnostic ultrasound imaging for the assessment of body fluid status in this patient group.
Normal ranges have been established for neonates for the following indices:
The difference in the IVC1/AAB index between the groups of healthy and sick children is not statistically significant (p > 0.05). This means that it is necessary to measure the inferior vena cava diameter in the inspiratory phase (when the diameter of the vein is the smallest, the vein is most collapsed). Therefore, the IVC2/AAB index and CI are useful for the assessment of body fluid status.
Due to the short duration of the measurement, nonpainful and non-invasive course of the examination and relatively easy access to equipment, this procedure may be used in the everyday practice of neonatologists.
Conflict of interest
Authors do not report any financial or personal connections with other persons or organizations, which might negatively affect the contents of this publication and/or claim authorship rights to this publication.