Future lines of research on phase angle: Strengths and limitations.

Bioelectrical impedance analysis (BIA) is the most widely used technique in body composition analysis. When we focus the use of phase sensitive BIA on its raw parameters Resistance (R), Reactance (Xc) and Phase Angle (PhA), we eliminate the bias of using predictive equations based on reference models. In particular PhA, have demonstrated their prognostic utility in multiple aspects of health and disease. In recent years, as a strong association between prognostic and diagnostic factors has been observed, scientific interest in the utility of PhA has increased. In the different fields of knowledge in biomedical research, there are different ways of assessing the impact of a scientific-technical aspect such as PhA. Single frequency with phase detection bioimpedance analysis (SF-BIA) using a 50 kHz single frequency device and tetrapolar wrist-ankle electrode placement is the most widely used bioimpedance approach for characterization of whole-body composition. However, the incorporation of vector representation of raw bioelectrical parameters and direct mathematical calculations without the need for regression equations for the analysis of body compartments has been one of the most important aspects for the development of research in this area. These results provide new evidence for the validity of phase-sensitive bioelectrical measurements as biomarkers of fluid and nutritional status. To enable the development of clinical research that provides consistent results, it is essential to establish appropriate standardization of PhA measurement techniques. Standardization of test protocols will facilitate the diagnosis and assessment of the risk associated with reduced PhA and the evaluation of changes in response to therapeutic interventions. In this paper, we describe and overview the value of PhA in biomedical research, technical and instrumental aspects of PhA research, analysis of Areas of clinical research (cancer patients, digestive and liver diseases, critical and surgical patients, Respiratory, infectious, and COVID-19, obesity and metabolic diseases, Heart and kidney failure, Malnutrition and sarcopenia), characterisation of the different research outcomes, Morphofunctional assessment in disease-related malnutrition and other metabolic disorders: validation of PhA with reference clinical practice techniques, strengths and limitations. Based on the detailed study of the measurement technique, some of the key issues to be considered in future PhA research. On the other hand, it is important to assess the clinical conditions and the phenotype of the patients, as well as to establish a disease-specific clinical profile. The appropriate selection of the most critical outcomes is another fundamental aspect of research.

Phase angle in localized bioimpedance measurements to assess and monitor muscle injury.

Localized bioimpedance (L-BIA) measurements are an innovative method to non-invasively identify structural derangement of soft tissues, principally muscles, and fluid accumulation in response to traumatic injury. This review provides unique L-BIA data demonstrating significant relative differences between injured and contralateral non-injured regions of interest (ROI) associated with soft tissue injury. One key finding is the specific and sensitive role of reactance (Xc), measured at 50 kHz with a phase-sensitive BI instrument, to identify objective degrees of muscle injury, localized structural damage and fluid accretion, determined using magnetic resonance imaging. The predominant effect of Xc as an indicator of severity of muscle injury is highlighted in phase angle (PhA) measurements. Novel experimental models utilizing cooking-induced cell disruption, saline injection into meat specimens, and measurements of changing amounts of cells in a constant volume provide empirical evidence of the physiological correlates of series Xc as cells in water. Findings of strong associations of capacitance, computed from parallel Xc (XCP), with whole body counting of 40-potassium and resting metabolic rate support the hypothesis that parallel Xc is a biomarker of body cell mass. These observations provide a theoretical and practical basis for a significant role of Xc, and hence PhA, to identify objectively graded muscle injury and to reliably monitor progress of treatment and return of muscle function.

Phase angle as an index of physiological status: validating bioelectrical assessments of hydration and cell mass in health and disease.

Bioelectrical impedance (BI) is a practical method to assess body composition in health and disease. This method relies on the passive conduction of an applied, safe, low-level alternating current through water and electrolytes in the body. Using a phase-sensitive device, BI yields measurements of impedance (Z) and its components, resistance (R) and reactance (Xc), that are related geometrically as phase angle (PhA). In vitro studies provide empirical evidence relating BI measurements to physiological variables. Cooking raw food samples results in greater decreases in PhA, predominantly Xc, with smaller reductions R indicating destruction of cell membrane integrity with simultaneous movement of fluid from intracellular to extracellular space. Infusion of saline into a cell-free model shows a proportional decrease in R with increases in volume. Saline infusion in a composite model of cells disproportionately decreases Xc and PhA, compared to R, demonstrating greater relative expansion of extracellular water (ECW) with a lesser relative increase in total fluid volume. Surgical patients treated with fluid infusion and diuresis demonstrate changes in Xc predominantly indicating relative changes in ECW with lesser variations in R indicating fluctuations in total fluid volume. Proteomics studies disclose strong independent associations of PhA with protein markers of fluid overload and protein proliferation. Interpretations of PhA measurements for body cell mass should be examined in the context of hydration status.

Overhydration Assessed Using Bioelectrical Impedance Vector Analysis Adversely Affects 90-Day Clinical Outcome among SARS-CoV2 Patients: A New Approach.

Background: COVID-19 has taken on pandemic proportions with growing interest in prognostic factors. Overhydration is a risk factor for mortality in several medical conditions with its role in COVID-19, assessed with bioelectrical impedance (BI), gaining research interest. COVID-19 affects hydration status. The aim was to determine the hydration predictive role on 90 d survival COVID-19 and to compare BI assessments with traditional measures of hydration. Methods: We studied 127 consecutive COVID-19 patients. Hydration status was estimated using a 50 kHz phase-sensitive BI and estimated, compared with clinical scores and laboratory markers to predict mortality. Results: Non-surviving COVID-19 patients had significantly higher hydration 85.2% (76.9−89.3) vs. 73.7% (73.2−82.1) and extracellular water/total body water (ECW/TBW) 0.67 (0.59−0.75) vs. 0.54 (0.48−0.61) (p = 0.001, respectively), compared to surviving. Patients in the highest hydration tertile had increased mortality (p = 0.012), Intensive Care Unit (ICU) admission (p = 0.027), COVID-19 SEIMC score (p = 0.003), and inflammation biomarkers [CRP/prealbumin (p = 0.011)]. Multivariate analysis revealed that hydration status was associated with increased mortality. HR was 2.967 (95%CI, 1.459−6.032, p < 0.001) for hydration and 2.528 (95%CI, 1.664−3.843, p < 0.001) for ECW/TBW, which were significantly greater than traditional measures: CRP/prealbumin 3.057(95%CI, 0.906−10.308, p = 0.072) or BUN/creatinine 1.861 (95%CI, 1.375−2.520, p < 0.001). Hydration > 76.15% or ECW/TBW > 0.58 were the cut-off values predicting COVID-19 mortality with 81.3% and 93.8% sensitivity and 64 and 67.6% specificity, respectively. Hydration status offers a sensitive and specific prognostic test at admission, compared to established poor prognosis parameters. Conclusions and Relevance: Overhydration, indicated as high hydration (>76.15%) and ECW/TBW (>0.58), were significant predictors of COVID-19 mortality. These findings suggest that hydration evaluation with 50 kHz phase-sensitive BI measurements should be routinely included in the clinical assessment of COVID-19 patients at hospital admission, to identify increased mortality risk patients and assist medical care.

Phase angle and standardized phase angle from bioelectrical impedance measurements as a prognostic factor for mortality at 90 days in patients with COVID-19: A longitudinal cohort study.

BACKGROUND & AIMS: Severe acute COVID-19 has taken on pandemic proportions with growing interest in identification of prognostic factors for mortality. Standardized bioelectrical impedance (BI) phase angle (SPhA), which is PhA adjusted by age and sex, has been related to mortality in patients with several diseases but never investigated in COVID-19. Inflammation, a consequence of COVID-19 infection, affects fluid status (hydration) and can be identified with PhA. The aim of this study was to determine the predictive role of PhA on 90 days survival of adults with COVID-19. METHODS: We studied 127 consecutive patients diagnosed with COVID-19. BI measurements determined with a 50 kHz phase-sensitive BI device, body composition parameters and laboratory markers were evaluated as predictors of mortality. RESULTS: Non-surviving COVID-19 patients had significantly lower PhA and SPhA values (p < 0.001) and increased hydration (p < 0.001) compared to surviving patients. Patients in the lowest SPhA quartile had increased (p < 0.001) mortality and hospital stay, hyperhydration (p < 0.001), increased inflammation biomarkers [CRP (p < 0.001)], decreased nutritional parameters: body mass cell index [BCMI (p < 0.001) albumin (p < 0.001)], and reduced other biomarkers [D-dimer (p = 0.002)]. Multivariate analysis (Cox regression) revealed that PhA and hydration status, adjusted for age, sex, BMI, diabetes, hypertension, dyslipidaemia or heart disease, were associated (p < 0.001) with increased mortality. The hazard ratio was 2.48 (95% CI, 1.60-3.84, p < 0.001) for PhA and 1.12 (95% CI, 1.04-1.20, p = 0.003) for hydration percentage. PhA <3.95° was the cut-off for predicting mortality in acute COVID-19 with 93.8% sensitivity and 66.7% specificity. PhA offers greater sensitivity as a predictive prognostic test at admission, compared to the established analytical parameters of poor prognosis (CRP, lymphocytes, prealbumin). CONCLUSIONS: Low PhA (<3.95°), independent of age, sex, BMI, and comorbidities, is a significant predictor of mortality risk in COVID-19. These findings suggest that the evaluation of body composition with single-frequency phase-sensitive BI measurements should be included in the routine clinical assessment of COVID-19 patients at hospital admission to identify patients at increased mortality risk.

Classification of Hydration in Clinical Conditions: Indirect and Direct Approaches Using Bioimpedance.

Although the need to assess hydration is well recognized, laboratory tests and clinical impressions are impractical and lack sensitivity, respectively, to be clinically meaningful. Different approaches use bioelectrical impedance measurements to overcome some of these limitations and aid in the classification of hydration status. One indirect approach utilizes single or multiple frequency bioimpedance in regression equations and theoretical models, respectively, with anthropometric measurements to predict fluid volumes (bioelectrical impedance spectroscopy-BIS) and estimate fluid overload based on the deviation of calculated to reference extracellular fluid volume. Alternatively, bioimpedance vector analysis (BIVA) uses direct phase-sensitive measurements of resistance and reactance, measured at 50 kHz, normalized for standing height, then plotted on a bivariate graph, resulting in a vector with length related to fluid content, and direction with phase angle that indexes hydration status. Comparison with healthy population norms enables BIVA to classify (normal, under-, and over-) and rank (change relative to pre-treatment) hydration independent of body weight. Each approach has wide-ranging uses in evaluation and management of clinical groups with over-hydration with an evolving emphasis on prognosis. This review discusses the advantages and limitations of BIS and BIVA for hydration assessment with comments on future applications.