Following cardiac surgery for CHD, there are many factors known to influence paediatric ICU length of stay, such as age, the complexity, and duration of the surgical procedure, including cardiopulmonary bypass and aortic cross-clamp time, delayed sternal closure, pre-existing comorbidities, malnutrition, hospital-acquired infections, fluid overload, and low cardiac output syndrome.Reference Marino and Magee 1 – Reference Sampaio, O’Hearn, Reddy and Menon 4 Objective preoperative assessments may more accurately identify those children at risk of prolonged paediatric ICU stay, facilitating specific paediatric ICU management strategies allowing for better utilisation of paediatric ICU resources.
The aim of this study was to investigate the predictive value of a preoperative measures of bioelectrical impedance spectroscopy phase angle 200/5° in children admitted to paediatric ICU following cardiac surgery.
Methods and materials
Children (0–16 years) with CHD undergoing cardiac surgery were prospectively enrolled (March, 2015–April, 2017) at a single tertiary centre. Bioelectrical impedance spectroscopy phase angle measurements were collected at baseline (day before surgery). Exclusion criteria were children with a permanent pacemaker and those receiving corticosteroids.
Bioelectrical impedance spectroscopy measurements
Bioelectrical impedance spectroscopy is validated for use in a wide range of paediatric patients. Phase angle depends on the opposition to the flow of electrical current (resistance) and the effect of the capacitive ability of cell membranes to impede the current (reactance). Phase angle is negatively associated with resistance and positively associated with reactance and has been used to quantify cell membrane integrity (reactance) and the extent of fluid redistribution between intracellular and extracellular fluid compartments (resistance).Reference Marino, Meyer and Johnson 5 Bioelectrical impedance spectroscopy measurements were made using ImpediMed SFB7 (Pinkenba, QLD, Australia), a single-channel tetra-polar device able to measure resistance and reactance across 256 frequencies. Measurements were made using a standard tetrapolar electrodes distribution,Reference Marino, Meyer and Johnson 5 on the palms of hands and the soles of the feet of children in the supine position with arms and legs apart (Fig 1). Bioelectrical impedance spectroscopy phase angle 200/5° was calculated by dividing the phase angle at 200° by the phase angle at 5°. This measurement was used for analysis.Reference Azevedo, Moore and de Matos 6
Figure 1 Bioelectrical impedance spectroscopy electrodes placement in a tetrapolar position – for example, hands and feet.
Postoperative fluid management
In the first 12–24 hours following cardiac surgery, patients are fluid-restricted to 2 ml/kg/h, which is 48/kg/day. This is usually liberalised to 3 and then 4 ml/kg/h, which is 72–96 ml/kg/day, on consecutive postoperative days depending upon circulatory status and cumulative fluid balance.
Patient and operation characteristics
Demographic data (n=50) were collected (Table 1). Prolonged paediatric ICU length of stay was defined as ⩾96 hours, based on the mean paediatric ICU length of stay in the United Kingdom. 7
Table 1 Baseline characteristics values.
ACC=aortic cross-clamp; BIS=bioelectrical impedance spectroscopy; CPB=cardiopulmonary bypass; PA=phase angle; PIM=Paediatric Index of Mortality; PIM2=Paediatric Index of Mortality version 2; PIM2r=Paediatric Index of Mortality version 2r; PICU-LOS=paediatric ICU length of stay; RACHS=risk adjusted congenital cardiac surgery
Mean±standard deviation
Statistical analysis
SPSS version 24 (SPSS, Chicago, Illinois, United States of America) was used for statistical analyses. Median and interquartile ranges were used to describe the data sets, and correlation between variables of interest was assessed with statistically significant relationships, being further tested using multiple linear regression models. Statistical significance was set at a p-value of <0.05.
Results
Bioelectrical impedance spectroscopy phase angle 200/5° measurements were completed in 50 children before surgery. In all, 59% were male and 41% were female. Nutritional status was evaluated preoperatively; moderate malnutrition was defined as height-for-age z score ⩽−2; and 16% of children met this criterion.
Relationships between clinical variables and paediatric ICU length of stay
There were significant positive correlations between paediatric ICU length of stay and bioelectrical impedance spectroscopy phase angle 200/5° (n=50, r=0.46, p<0.001) and fluid balance on day 0 (n=50, r=0.46, p<0.001) (Table 2). There were also significant correlations between bioelectrical impedance spectroscopy phase angle 200/5° and fluid balance on day 0 (n=50, r=−0.3, p=0.03) and a significant negative correlation with height-for-age z score (n=50, r=−0.3, p=0.03) (Fig 2a and c). Bioelectrical impedance spectroscopy phase angle 200/5° remained statistically associated with paediatric ICU length of stay when entered into a linear regression model (p=0.029). Baseline bioelectrical impedance spectroscopy phase angle 200/5° reflects the volume of water in a variety of partitioned body compartments (total body water, extracellular fluid, and intracellular fluid); the relationship with fluid balance on day 0 and paediatric ICU length of stay suggests that this could be used to identify children at risk of prolonged paediatric ICU length of stay.
Figure 2 ( a ) The relationship between bioelectrical impedance spectroscopy (BIS) phase angle 200/5° and paediatric ICU (PICU) length of stay (n=50, r=0.46, p<0.001). ( b ) The relationship between BIS phase angle 200/5° and fluid balance (n=50, r=0.3, p=0.03). ( c ) The relationship between BIS phase angle 200/5° and height-for-age z score (n=50, r=−0.3, p=0.03).
Table 2 Clinical variables and relationship to paediatric ICU length of stay (PICU-LOS) and bioelectrical impedance spectroscopy (BIS) phase angle (PA) 200/5°.
Discussion
Recent work in our paediatric ICU had found that children with CHD with a bioelectrical impedance spectroscopy phase angle measurement of ⩽2.7° had a four-fold increased risk of a prolonged paediatric ICU length of stay.Reference Marino, Meyer and Johnson 5 Shime et alReference Shime, Ashida and Chihara 8 previously showed that children undergoing surgery for CHD who had a 20% difference between the bioelectrical impedance spectroscopy phase angle 50° measured preoperatively and postoperatively – bioelectrical impedance analysis ratio of <0.8 – had a higher morbidity and mortality compared with those with a bioelectrical impedance analysis ratio of 1.0. In this study, we were able to demonstrate a statistically significant relationship between bioelectrical impedance spectroscopy phase angle 200/5° and paediatric ICU length of stay and positive fluid balance the day following surgery. A preoperative estimate of risk may allow for earlier identification and more targeted fluid management therapy during the postoperative period.
The identification of reliable objective preoperative prognostic indices of paediatric ICU length of stay in children scheduled to undergo surgery for the correction or palliation of CHD may influence strategies for their postoperative paediatric ICU fluid management. Measures of bioelectrical impedance spectroscopy phase angle measure cell capacitance and membrane integrity.Reference da Silva, Berbigier, Rubin Bde, Moraes, Correa Souza and Schweigert Perry 9 Published data in adults suggest that bioelectrical impedance spectroscopy phase angle 200/5° reflects the volume of water in a variety of partitioned body compartments – total body water, extracellular fluid, and intracellular fluid.Reference Kuchnia, Earthman and Teigen 12 There is a relative paucity of evidence to demonstrate the utility of bioelectrical impedance spectroscopy phase angle 200/5° in children. Previously published data from our group have demonstrated a relationship between preoperative bioelectrical impedance spectroscopy phase angle 50° and paediatric ICU length of stay, but it might simply be a reflection of the frequency chosen to measure bioimpedance.Reference Marino, Meyer and Johnson 5
Alternating electrical current at a higher frequency (200 Hz) bioelectrical impedance spectroscopy is considered to be representative of total body water, whereas bioelectrical impedance spectroscopy measurements at lower frequencies reflect extracellular fluid compartments, as current at this frequency cannot pass cell membranes with such efficiency. Therefore, using the ratio paired comparisons of bioelectrical impedance spectroscopy measurements at different frequencies have been used to estimate extracellular compared with intracellular distribution of fluid in a variety of diseases, 10 , Reference Thomas, Ward and Cornish 11 but this is the first time these measurements have been compared with clinical outcomes in a paediatric population undergoing surgery for the correction/palliation of CHD.
Bioelectrical impedance spectroscopy phase angle 200/5° has been shown to be a marker of clinical outcomes and nutritional status in critically ill adults. Furthermore, in this setting, bioelectrical impedance spectroscopy phase angle 200/5° also appears to be a measure of functional outcome – for example, with lower bioelectrical impedance spectroscopy phase angle values seen in patients with poor handgrip strength.Reference Kuchnia, Earthman and Teigen 12 In our work, there appears to be a relationship between preoperative bioelectrical impedance spectroscopy phase angle 200/5° measure and paediatric ICU length of stay, in addition to relationships with height-for-age Z scores and day 0 postoperative fluid balance. These results suggests that a baseline measure of bioelectrical impedance spectroscopy phase angle 200/5° may be useful in identifying children with preoperative changes to cellular resistance and subsequent postoperative resilience. As bioelectrical impedance spectroscopy phase angle changes precede anthropometrical changes, developing cut-off values from a larger cohort may aid the preoperative identification of those children who are at risk of a prolonged paediatric ICU length of stay, ensuring that aspect of fluid and nutritional management are optimised. Although the underlying relationship between bioelectrical impedance spectroscopy phase angle and nutritional status is not completely understood, there is increasing recognition that the use of raw bioelectrical impedance spectroscopy phase angle measures within a clinical setting can increase the predictive accuracy of those children who may be at risk of poorer postoperative clinical outcomes, thereby requiring greater resources during their paediatric ICU stay.Reference Marino, Meyer and Johnson 5
A limitation of this study is that although our study has demonstrated some significant relationships between bioelectrical impedance spectroscopy measurements and clinical outcome as the study numbers are small, further work is required to determine clinically effective cut-off values of bioelectrical impedance spectroscopy phase angle 200/5° in a larger cohort of children with CHD. These results may only be specific to this patient cohort and would require validation in different clinical settings. In addition, there was a wide age range of children within this study, and focusing on the age group that is at highest risk – for example, <12 months of age – may be of benefit in the future.
Conclusion
Preoperative bioelectrical impedance measurements of bioelectrical impedance spectroscopy phase angle 200/5° in children with CHD are easy and safe to complete. Using phase bioelectrical impedance spectroscopy phase angle 200/5° may help to better identify those children at risk of prolonged paediatric ICU length of stay.
Acknowledgements
The authors thank Charlotte Jewell, Medical Student, for contributing to data collection, and specialist Cardiac Liaison and Practice Nurses Colette Cochran, Gill Harte, Doreen Macfail, Katy Simons, and Carolyn Boyles for their assistance in identifying potential recruits. The authors also thank all of the children and their families for agreeing to participate in the study and NIHR Southampton Biomedical Research Centre and Nutricia (UK) for their support.
Authors’ Contribution
All authors have made substantial contributions to all areas of this manuscript data collection and statistical analyses. All authors edited, read, and approved the final manuscript.
Financial Support
The study was supported by NIHR Southampton Biomedical Research Centre Commercial & Enterprise Incubator Fund (Study number: RHM CH10742). L.V.M. was supported by a post-doctoral fellowship award from NIHR Health Education England (Wessex). This work is also part of independent research completed by L.V.M. arising from a Health Education England/NIHR Clinical Lectureship (ICA-CL-2016-02-001) supported by the National Institute for Health Research. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research, Health Education England, or the Department of Health.
Conflicts of Interest
None.
Ethical Standards
This study was approved by the NHS ethics committee (West Midlands, reference 15/WM/0020).
