Noninvasive Bioreactance-Based Fluid Management Monitoring: A Review of Literature

Introduction

Body fluid balance is an independent predictor of mortality. This is even more relevant in context of replenishment of fluid in conditions like shock—wherein less or more replenishment is equally hazardous. To depict it another way, the fluid-volume versus complication curve can be plotted in U-shape, with minima in the middle physiological region as shown in Fig. 1.

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Fig. 1

Fluid volume versus complication curve.¹

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At the same time, it is also known that in critical conditions, body fluids function through volume expansion and in addition to their actions as a matrix of various metabolic activities, they also act as the transport vehicle of nutrition, oxygenation, and excretion. Thereby, the replenished fluid is contextually a drug with low therapeutic index (analogous to antiarrhythmic drug which lead to arrhythmia in absence as well as when in excess) (Fig. 2).

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Fig. 2

Daily fluid replenishment and occurrence of complications.²

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The study was performed upon 23,513 severe sepsis/septic shock cases admitted to intensive care unit (ICU) and for each liter of fluid over and above 5 L, risk-adjusted excess mortality is seen. Mortality increased by 2.3% (95% confidence interval 2.0–2.5%, p = 0.005) for each 1 L of fluid and hospital costs increased by $999.² Thus, the propensity model analysis looking at “mortality and fluid administration” using age and “acute conditions on admission” supports the hypothesis that fluid balance is an independent predictor of mortality.

Recently, researches have concluded that “considering the changing adult cardiac surgery patient population and continuous advances in health care, dynamic models are preferred over static models for assessing volume responsiveness of a patient in shock.”³ Accordingly, most recent guidelines, namely National Institute of Health and Clinical Excellence (U.K.) (2011), SFAR (French Society of Anaesthesia and Intensive Care Medicine; France) (2013), European Society of Intensive Care Medicine (2014), DGAI (German Society of Anaesthesiology and Intensive Care Medicine; Germany) (2014), National Quality Forum (2015), and Society of Critical Care Medicine (SCCM 2015) Surviving Sepsis Campaign (SSC 2013, 2017) have endorsed dynamic modeling.

Against the passive leg raising (PLR) and trending 500 mL fluid challenge, a minor bolus challenge of 300 was compared for assessing the fluid responsiveness—all the methods imply a play of Frank–Starling law. PLR-induced changes in cardiac output (CO) reliably predict the response of CO to volume expansion in adults with acute circulatory failure. PLR-induced increase of aortic blood flow ≥ 10% predicts fluid responsiveness with a sensitivity of 97% and a specificity of 94%.⁴

The question is that “do all hemodynamically unstable patients respond to a bolus of intravenous fluids—nearly half will not respond to intravenous bolus?” In a meta-analysis of 50 ICU studies and 2,260 patients, only half of patients were fluid responsive (at 95% confidence interval, 42–56%, with a sensitivity of 88%, and specificity of 92%).⁴

This fact may manifest because it is also a fact that on the flatter right extreme of the Frank–Starling curve, the same amount of the bolus fluid is not as effective in increasing the stroke volume as at the steeper part of the curve (Fig. 3).

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Fig. 3

Refractory (or less responsive) stroke volume on fluid responsiveness test (adapted from Cecconi M, Parsons AK, Rhodes A. What is a fluid challenge?⁵

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Moreover, when PLR effects are assessed by changes in pulse pressure, the specificity of the PLR test remains acceptable, but its sensitivity is poor. Still PLR followed by measurement of CO or related parameters may be the most useful tests for predicting fluid responsiveness in hemodynamically unstable adults.⁴, ⁶ Although the usefulness in assessment of respiratory variation in the vena cava requires confirmatory studies.⁴

Other commonly used CO measurement methods include indirect Fick methods, thermodilution (TD), Doppler ultrasound or echocardiography, partial carbon dioxide rebreathing, thoracic electrical bioimpedance, and magnetic resonance imaging. TD via the pulmonary artery catheter (PAC) is still considered to be the gold standard method in the clinical setting.⁷

Coming to the inherent technological difference, a device based on bioreactance (Starling, Baxter Inc. Deerfield, United States) works on phase shift or time delay (Fig. 4A), while bioimpedance works on the amplitude of the thoracic impedance. The flow of blood in the thorax introduces a time delay or “phase shift” in STARLING signal. These signal changes have been further correlated to the known TD CO of 65,000 patient samples in multiple clinical settings.

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Fig. 4

Parameter measured in bioimpedance (A: left) versus bioreactance (B: right).

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Unlike bioimpedance, bioreactance is not affected by the size of the patient, thoracic fluids (e.g., pleural effusion/pulmonary edema), or position of sensors. And here lies the advantage of a device based on bioreactance if utility and cost-effectiveness parameters are acceptable.

Method

We searched Scholar, MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in the COCHRANE Library. The Medical Subject Headings terms “Fluid Management,” “Fluid responsiveness,” and “Non Invasive fluid management monitoring,” “Bio-Reactance,” “STARLING” were used. Additional studies were identified by review of the reference sections of all eligible studies. The aim of this review article is to bring together the evidences with bioreactance-based fluid management monitoring in critically ill patients.

STARLING

The STARLING system (Fig. 5) is equipped with four sensor pads. Each pad contains two sensors, the outer sensor is a transmitting electrode and the inner sensor is a receiving electrode. The sensors are applied around the heart on the chest or back (there is no need for exact positioning).

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Fig. 5

STARLING: working principle (phase shift).

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The STARLING monitor induces a 75 KHz AC current to the thorax via the outer sensors and receives the voltage via the inner sensors. It then measures the time delay/phase shift (as depicted in Fig. 4A) between the induced current and the received voltage continuously, thus building the STARLING signal. The final mechanistic flowchart is as shown in Fig. 6.

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Fig. 6

STARLING: A noninvasive fluid management monitoring system.

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STARLING Validation Data with FloTrac, Esophageal Doppler Monitoring, and Thermodilution

CO measurements obtained from bioreactance-based monitoring and TD were simultaneously recorded minute-by-minute and compared in 110 patients. Bioreactance-based monitoring was evaluated for the accuracy, precision, responsiveness, and reliability for detecting CO changes. Total of 65,888 pairs of CO measurements were collected from 110 patients.⁸

In this study,⁷ the authors concluded that bioreactance-based fluid monitoring system had acceptable accuracy, precision, and responsiveness for CO monitoring in patients experiencing a wide range of circulatory situations. In yet another study,⁹ it was found that CO measured via bioreactance is precise and reliably measures CO at rest and changes in CO with vasodilator challenge in patients with pulmonary hypertension.

STARLING: Implementing Noninvasive Fluid Management Monitoring in Indian Setting

Because of the limitations of bioimpedance devices, newer methods of processing the impedance signal have been developed. Human thorax and thoracic content is reason for their resistance (R) and capacitance (C), which together create the thoracic impedance (Zo), when a current is passed through thorax. Phase shifts can occur only because of pulsatile flow. The overwhelming majority of thoracic pulsatile flow stems from the aorta. Therefore, the STARLING signal is correlated almost wholly with aortic flow. Furthermore, because the underlying level of thoracic fluid is relatively static, neither the underlying levels of thoracic fluids nor their changes induce any phase shifts and do not contribute to its signal.¹⁴

The CO as measured by bioreactance has been shown to highly correlate with that measured by TD and pulse contour analysis.¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹ Squara et al¹⁶ compared the STARLING system with PAC-derived CO in 110 patients after cardiac surgery. The reported bias was ± 0.16 L/min; Limits of Agreement (LOA) on Bland and Altman representation of ± 1.04 L/min with a relative error of 9%. The precision of the STARLING system was better than that of TD, with the device being able to track changes in CO accurately.

In a study of three ICUs (70 patients), Raval et al¹⁵ reported a bias of –0.09 L/min and an LOA of ± 2.4 L/min, with the STARLING system closely tracking changes in the TD CO. Rich et al¹⁷ performed right-heart catheterization in 24 patients with pulmonary hypertension. Simultaneous CO measurements were performed using TD, STARLING, and the Fick methods at baseline and after adenosine vasodilator challenge. CO measured by the STARLING system was significantly more precise than that of TD. The adenosine challenge resulted in a similar mean increase in CO with each method. The accuracy of STARLING was assessed in hemodynamically unstable ICU patients and healthy volunteers after PLR and fluid challenges using carotid and brachial arterial Doppler ultrasound flow (mL/min) as the reference technique and confirmed almost same as in a previous study¹⁹, ²⁰ where almost 100% concordance was found between fluid responsiveness as determined by carotid flow and the NICOM system.

Benomar et al²¹ showed that the NICOM system could predict fluid responsiveness accurately from changes in CO during PLR. As part of goal-directed perioperative therapy in patients undergoing major surgery, Waldron et al²² compared fluid responsiveness with an esophageal Doppler monitor and the NICOM system. Notwithstanding the limitations of esophageal Doppler monitoring (as discussed previously), there was a good agreement between these technologies.

STARLING system, personalized for fluid therapy:

1. Provides a dynamic assessment of fluid responsiveness—accurately, precisely, and 100% noninvasively. It supports individualized fluid therapy without requiring an invasive arterial or central line. It may reduce the risk of hospital-acquired infections and other complications. It has been independently validated against PAC, considered to be current gold standard in fluid monitoring therapy. Accuracy not affected by vasopressors or shock state and works in mechanically ventilated and spontaneously breathing patient. In Kansas trial also discussed previously, a retrospective analysis¹¹ of 200 sepsis/septic shock patient has shown a cost–benefit of $14,498 per patient as result of reduction in ICU length of stay, acute dialysis, and mechanical ventilation. Although this was the study conducted in United States, its implication may extend to developing countries with significant health care burden like India. In view of high recurring costs associated with other invasive or minimally invasive hemodynamic monitoring modalities for the disposables, noninvasive disposable sensor pads used for STARLING can further reduce the recurring cost and economic burden of Indian patient.

• STARLING system seems to be accurate, precise, and reasonably validated technology with over 500 patients in published clinical studies. Multiple clinical settings (ICU/operating room/emergency department/exercise laboratory/out of hospital) against all major technologies (Swan Ganz, Pulse Contour, Doppler, Fick) with over 100 peer-reviewed publications.

Conclusion

Overall, given the clinical apropos, economic benefits with STARLING-based stroke volume-guided fluid therapy, its impact on current clinical practice would mostly rely upon the advantage of noninvasiveness (and consequential benefits like less chances of procedural cost/pain/infection/hospital stay, etc.) and wide spectrum of patient applicability.