Accuracy of the transpulmonary ultrasound dilution method for detection of small anatomic shunts.

The purpose of this study was to investigate the qualitative and quantitative accuracy of transpulmonary ultrasound dilution (UD) (COstatus™, Transonic Systems) for the detection of small anatomic shunts. It was a prospective, observational study in a multi-disciplinary pediatric intensive care unit. Seventy-three critically ill children (67 post cardiac surgery), with a median (IQR) age of 10 (3-50.3) months and a median (IQR) weight of 8 (3.43-13) kg were enrolled. Ultrasound dilution (UD) measurements were performed on patients within 1 h of undergoing two-dimensional echocardiography, which was used as the comparator technique. Shunt was diagnosed by characteristic changes on the UD curve shape, and was considered "test-positive" only if two or more measurements suggested the presence of the shunt. The UD technology also provided an estimate of pulmonary to systemic blood flow ratio (Qp:Qs). 12/73 (16.4 %) patients had a shunt identified by both UD and echocardiography. The overall accuracy (95 % CI) was 86.1 % (75.6-96.6 %), with a sensitivity of 85.7 % (57.2-98.2 %) and specificity of 86.4 % (75.0-94.0 %). The estimated Qp:Qs ranged from 0.7 to 1.4, which was consistent qualitatively with the echocardiographic findings on color flow doppler. Shunt was detected by UD alone in eight children; six of these had clinical conditions known to compromise dilution curve analysis (valve regurgitation, asymmetric pulmonary blood flow). Shunt was detected by echocardiography alone in two children; in both cases the shunt was tiny. UD is an accurate method for the detection of small anatomical shunts, both qualitatively and quantitatively.

Accuracy of dilution techniques for access flow measurement during hemodialysis.

Access flow is now widely measured by creating artificial recirculation with the dialysis lines reversed and using dilution methods that sense either ultrasound velocity, electrical impedance, optical, or thermal changes. This study identifies and quantifies factors that influence the accuracy of access flow measurements and recommends ways to reduce these errors. Two major sources of access flow measurement error are identified, arising firstly from the second pass of the indicator by recirculation through the cardiopulmonary system (cardiopulmonary recirculation, CPR), and secondly from changes in venous line blood flow (Qb) and vascular access flow induced by the pressure of venous bolus injections. These errors are considered from theory, by direct measurement of access flow in a sheep model, and by analysis of clinical data. Two extremes for the venous introduction of indicator can be considered in access flow measurements, a slow infusion, which perturbs neither the venous line flow nor access flow but increases the error attributable to the second pass of the indicator by recirculation through cardiopulmonary system, or rapid injection, which eases separation of the second pass of the indicator signal but generates changes in the venous flow and access flow. If CPR is not eliminated, the area added to that of the first pass of indicator ranges up to 40%. Good time resolution could permit the separation of the areas generated by the first and second passage of the indicator. In sheep experiments, injections of 5 or 10 mL into a venous port close to the vascular access caused Qb to change by 20% to 40%. Both the animal experiments and analysis of raw data collected during routine clinical dialysis showed that moving the injection site sufficiently far from the patient, before or into the venous bubble trap, reduced the increase in Qb to only approximately 5% during the critical time when the concentration curve is changing for most tubing brands (Baxter, Belco, Gambro, Hospal, Medisystem, and National Medical Care). Because of the smaller volume of the venous bubble chamber in Cobe tubing (Cobe, Centrysystem 3), this brand showed approximately a 20% increase in Qb. Moving the site of bolus injections to before the bubble trap in the sheep experiments also eliminated the influence of changes in access flow. An additional error in access flow measurement of 20% or more arises from the use of flow reading taken from pump setting rather than a measured flow. The discrepancy between the real flow and pump setting is attributable to needle size, vascular access conditions, or pump calibration. The results show that problems can be minimized by using a dual sensor system that retains the precise timing necessary for separation of access recirculation from CPR; by accurate measurement of dialyzer blood flow; by moving the site of injection to before the venous bubble trap, sufficiently far from the patient, and correcting for any remaining deviations in flow in the venous line concurrent with the dilution curve.

Extravascular lung water in the exercising horse.

Seven Standardbred horses were exercised on a treadmill at speeds (approximately 12 m/s) producing maximal heart rate, hypoxemia, and a mean pulmonary arterial pressure of approximately 75 mmHg. Extravascular lung water was measured by using transients in temperature and electrical impedance of the blood caused by a bolus injection of cold saline solution. Lung water was approximately 3 ml/kg body wt when standing but did not increase significantly with exertion. We conclude that any increase in fluid extravasation from the pulmonary hypertension accumulates in the lung at a level that is less than that detectable by this method. At maximal exertion, the volume of blood measured between the jugular vein and the carotid artery increased by approximately 8 ml/kg, and the actively circulating component of the systemic blood volume increased by approximately 17 ml/kg with respect to corresponding values obtained when walking before exertion. These volume increases, reflecting recruitment and dilatation of capillaries, increase the area for respiratory gas exchange and offset the reduced transit times that would otherwise be imposed by the approximately eightfold increase in cardiac output at maximal exertion.

Novel method to measure access flow during hemodialysis by ultrasound velocity dilution technique.

This article presents the theory and bench validation of access flow measurement by ultrasound velocity dilution. Reversal of dialysis lines creates a zone of mixing in the vascular access, allowing the use of dilution technique for access flow measurement. The method of sound velocity dilution sensor calibration was analyzed. A single sensor system was investigated for blood circulation and isothermal injections. A dual sensor system was investigated with heated hypertonic saline circulation for both body temperature (isothermal) and room temperature (cold) injections. The accuracy of in vitro access flow measurement was studied on a two pump bench model, dialysis line flow was varied from 200 to 400 ml/min, access flow was varied from 300 to 2500 ml/min. For the dual sensor system, dilution access measurements tracked a gravimetrically calibrated in-line flow sensor within 3.25 +/- 0.34% for isothermal injections, and within 5.81 +/- 0.43% for cold injections. Measurements were repeatable within 3% independent of the temperature of the injected saline. For the single sensor system, results tracked the in-line flow sensor within 3.83 +/- 0.79%. These data show that access flow can be accurately measured by sound velocity dilution technique.

Clinical measurement of blood flow in hemodialysis access fistulae and grafts by ultrasound dilution.

Blood flow is a fundamental property of the hemodialysis access device. Periodic monitoring of flow could be useful for detection of impending access failure and prevention of underdialysis, but simple measurements of access flow during hemodialysis are not currently available. Flow in peripheral arteriovenous fistulas and grafts was examined using an indicator dilution technique while the patient's blood lines were reversed. The indicator was a bolus of normal saline detected by an ultrasound flow sensor clamped onto the patient's blood line. The ultrasound sensor measured blood flow in the tubing using an established transit-time method and simultaneously detected saline dilution of the blood from changes in the average cross sectional velocity of an ultrasound beam that illuminated the blood flowing through the tubing. Access flow was measured 110 times in 25 patients, 16 with loop grafts and 9 with native fistulas. Measured access flow ranged from 125 to 2860 ml/min. The mean error of duplicate measurements within patients was 5.0 +/- 3.8%. To assess the adequacy of saline mixing with the blood, access flow was measured at three dialyzer blood flow rates. In paired studies, no significant difference was observed in access flow measured at two lower dialyzer blood flow rates when compared to flow measured at 350 ml/min. A comparison with access flow measured by a duplex color Doppler technique in seven patients gave a mean error of 9.2 +/- 7.2% in paired studies. These data show that blood flow in peripheral arteriovenous grafts and fistulas can be measured accurately during hemodialysis using ultrasound velocity dilution.

Hemodialysis access recirculation measured by ultrasound dilution.

The most widely used clinical method for measuring recirculation in the access device is based on urea dilution. The three simultaneous blood samples required during hemodialysis interrupt the treatment, and results of chemical analysis are often delayed for several days. Alternatively, detecting recirculation by dilution of arterial blood caused by a bolus of normal saline injected into the venous blood line has several advantages. In this study, an ultrasound sensor clamped onto the arterial line entering the dialyzer was used to detect such dilution from a reduction in sound velocity observed in the saline diluted blood. Within the target range, the change in ultrasound velocity (ultrasound dilution) is linearly correlated with the dilution of whole blood by normal saline. The same sensor was also used to measure flow in the blood line using an established ultrasound transit-time method. During 34 hemodialyses in 28 patients, only 3 patients had detectable recirculation measured by ultrasound dilution. To further evaluate the sensitivity of the new method the dialysis lines were reversed during hemodialysis in the 25 patients with no recirculation. After this, all had detectable recirculation ranging from 10 to 60%. The mean error of duplicate measurements was 3.9 +/- 2.8%. Recirculation by ultrasound dilution correlated closely with recirculation measured by urea dilution (r = 0.9156, p < 001). The data suggest that the ultrasound dilution method is both sensitive and accurate. Ease of use and immediate availability of results added to the clinical usefulness of this method for evaluating the integrity of the hemodialysis access.

Extracorporeal recording of mouse hemodynamic parameters by ultrasound velocity dilution.

The use of mice as models for cardiovascular studies has traditionally been difficult because of their small size and the lack of appropriate instrumentation to perform fundamental measurements of cardiac output (CO) and total blood volume (TBV). The advent of transgenic techniques to develop mouse strains that mimic human disease makes the development of this instrumentation crucial. The current study outlines a novel technique for the determination of CO and TBV in the mouse using an extracorporeal arteriovenous (A-V) shunt, combined with the measurement of ultrasound dilution after the intravenous administration of small volumes of isotonic saline. The potential sources of error associated with Stewart-Hamilton dilution techniques were addressed by the research. The new techniques were applied in three anesthetized mice (27-36 gm). Isotonic saline (10-80 microl) was injected intravenously while measuring ultrasound dilution in the A-V shunt. The CO ranged from an average of 6.8+/-0.71 to 12.7+/-1.7 ml/min. Heart rates were not significantly altered by the intravenous administration of isotonic saline. The TBV ranged from 4.36+/-0.22 to 5.15+/-1.04 ml/100 gm. These results agree with the literature and suggest that these techniques will prove useful in cardiovascular studies of mice.

Use of an extracorporeal arteriovenous tubing loop to measure cardiac output in intensive care unit patients by ultrasound velocity dilution.

Thermodilution cardiac output (CO) measurement requires heart catheterization and is known as a risk factor. The existing cannula in the radial artery in intensive care unit (ICU) patients can be used to measure CO by ultrasound dilution (COus). An arteriovenous shunt between the radial artery and cubital vein was created using a 25 cm tubing loop. An ultrasound flow dilution sensor was clamped on the tubing and connected to a modified HD01 monitor (Transonic Systems, Inc., Ithaca, NY). Calibration injections of 1 ml 0.9% NaCl were injected into the tubing. An intravenous bolus injection consisted of 10-20 ml 0.9% NaCl. Simultaneously, CO was measured by thermal dilution (COth; MI 166A, Hewlett Packard, Andover, MA). Each value for COth or COus was based on the average of three to five injections. Blood flow through the shunt was 10 to 26 ml/min. The comparison was made on 14 patients. In 33 measurements, the regression equation was COth = -0.08 + 1.02 COus (r = 0.97). In 22 cases, the difference between COth and COus was less than 5%, in 9 cases it was in the range of 5-10%, and in 2 cases it was in the range of 10-20%. The presence of arterial and venous lines in an ICU setting obviates the need for cardiac catheterization for the determination of CO.

Volume of extravascular lung fluid determined by blood ultrasound velocity and electrical impedance dilution.

A hypertonic sodium chloride bolus passing through the lung has a sound velocity transient that is biphasic when it reaches the carotid artery. This transient is compatible with water moving into the hypertonic bolus from the lung parenchyma, thereby leaving the lung parenchyma hypertonic. Subsequently, as the bolus leaves the lung vasculature, water passes from the blood into the tissue to return the lung tonicity to baseline, giving a moment when net movement is zero, an instant of osmotic equilibrium. Concurrent measurements of impedance track the sodium chloride transient. A theoretic basis for the calculation of extravascular lung water is derived from the water transferred to the blood, the amount of sodium chloride moved from blood to the lung, and the increase in blood osmolarity measured at the moment of equilibrium. Examples from measurements on sheep suggest that two intravenous injections of hypertonic and isotonic sodium chloride, with observations of sound velocity and electrical impedance in the systemic arterial circulation (which could also provide the cardiac output), provide a basis for calculation of lung permeability, water and salt movements, and extravascular lung water estimation.

Theory and validation of access flow measurement by dilution technique during hemodialysis.

The theory shows that access flow can be measured by the dilution technique by reversal of the blood dialysis lines with the venous outlet facing the access stream: (1.) with one dilution sensor in arterial line and two injections Equation (6); (2.) with two matched dilution sensors on the venous line and on the arterial line and one injection Equation (8); (3.) with blood sampling as for recirculation measurement using BUN or other methods in Equation (12). In all cases, accurate measurement of hemodialysis blood flow is required. The results of this bench validation demonstrate that dialysis blood flows, in the clinical range of 200 to 350 ml/min or more, create good mixing conditions in a vascular access model. Accurate measurements are provided for all clinically significant ranges of access flows, needle positions, and vascular access inner diameters. This simple, non-invasive, and inexpensive technique shows great promise for routine diagnosis of vascular access failure in hemodialysis patients.

Cardiac output and central blood volume during hemodialysis: methodology.

Cardiovascular disease is the leading cause of mortality in patients whose lives depend on hemodialysis. We developed a method for measuring cardiac output (CO) and central blood volume (CBV) in hemodialyzed patients that may help to elucidate the mechanisms and consequences of cardiac disease in this population. This report describes the technique, focusing on the main sources of error and how they can be prevented. Three principal sources of error were identified: (1) access recirculation (existing or induced during injection); (2) the second pass of the indicator through the cardiopulmonary system, exacerbated by prolonging the duration of intravenous injection; and (3) the transit time of the indicator through the dialysis blood lines. After the algorithms were adjusted to prevent the above errors, the reproducibility of CO and CBV, expressed as the absolute percent deviation from the average of duplicates (3,488 values duplicated within 5 minutes), was 4.3 +/- 3.8% for CO and 4.1 +/- 3.8% for CBV. To determine the clinical value of routine CO and CBV measurements, morbid events (nausea, vomiting, and/or muscle cramps) were prospectively recorded in 73 randomly selected hemodialysis patients. CO and CBV were measured near the beginning and near the end of 98 dialysis sessions during which 28 morbid events were identified. In 10 of these sessions, where morbid events took place within 30 minutes of the measurements, CBV appeared to be a more sensitive indicator of morbid events than CO. We conclude that CO and CBV can be routinely and reliably measured during hemodialysis if precautions are taken to avoid specifically identified sources of error. Preliminary studies suggest that these measurements may have significant prognostic value.

Access flow measurement as a predictor of hemodialysis graft thrombosis: making clinical decisions.

Since the introduction of dilution methods for measurement of vascular access blood flow during hemodialysis, more than 170 publications addressing the accuracy, prognostic value, and economic impact of the technology have been presented. Recently researchers (Paulson et al.) have raised concerns about the accuracy of access flow measurements in predicting thrombosis. Our first objective was to address the inadequacies of the analysis by these authors. The second objective was to apply a statistically accepted three-step approach for clinical decision making to assess the utility of access flow surveillance (similar to the K/DOQI guidelines) in the prediction of thrombosis. These steps included 1) estimation of treatment thresholds based on harm-benefit analysis of fistulography-angioplasty versus thrombosis, 2) estimation of prior probability of thrombosis based on patient demographic and clinical characteristics, and 3) application of Bayes' theorem to evaluate whether flow test results provided information that could move patients across the treatment threshold, thus discriminating between patients who should be referred for fistulography-angioplasty and those who should not. These data and an analysis of recent publications show that the implementation of an access flow surveillance program decreases thrombosis rates in hemodialysis units and can significantly reduce the costs associated with hemodialysis access maintenance. We conclude that access flow monitoring (K/DOQI flow thresholds) is useful in the clinical decision-making process for thrombosis prediction across a wide range of demographic categories.

Quantification of lung microvascular injury with ultrasound.

Quantification of water and solute exchange rates across the lung microvascular barrier (LMB) may be an important early-warning indicator of pulmonary microvascular diseases such as acute respiratory distress syndrome. Our objective was to determine the degree to which osmotic water movement across the LMB induced by injection of hypertonic solutions of NaCl and glucose could be detected downstream from the lung with a specialized ultrasonic velocity (USV) transducer manufactured by Transonic Systems. We hypothesized that mathematical modeling of the osmotic transients (OT) would yield estimates of osmotic exchange parameters that were sensitive to microvascular injury. Two groups of six dogs were studied under baseline conditions and after injury with high dose (HD) or low dose (LD) oleic acid. Osmotic conductances (sigmaK(1), sigmaK(2)), and volumes (V(1), V(2)) of two extravascular spaces were estimated by fitting the mathematical model to the OT data. HD results (mean +/- standard error) indicated a significant decrease (by paired t test) in sigmaK(1) from 1.59 +/- 0.09 to 1.04 +/- 0.015 [ml h(-1) (mosm/l)(-1) g(-1) WLW)], an increase in sigmaK(2) from 0.20 +/- 0.08 to 0.32 +/- 0.12 [ml h(-1) (mosm/l)(-1) g(-1)], and a significant increase in V2 from 23.26 +/- 2.51 to 78.0 +/- 15.23 (ml) for NaCl injections. LD V2 estimated from NaCl increased significantly from 21.57 +/- 2.15 to 37.59 +/- 2.36 (ml), sigmaK2 increased from 0.09 +/- 0.03 to 0.17 +/- 0.04 and no significant change in sigmaK(1) was found. Baseline glucose sigmaK(1), sigmaK(2), and V1 in the LD series were 2.08 +/- 0.18, 0.64 +/- 0.19 [ml h(-1) (mosm/l)(-1) g(-1)] and 13.08 +/- 1.89 (ml), respectively, and did not change significantly with injury. We conclude that OT data measured by USV is a sensitive and informative indicator of LMB osmotic properties, and may be useful for quantification of LMB permeability changes due to acute injury. We further conclude that V(1) represents microvascular endothelial volume and V(2) is an estimate of interstitial volume.

Identifying a new reality: zero vascular access recirculation using ultrasound dilution.

Access recirculation measurements by blood urea nitrogen (BUN) sampling methods have come under recent criticism regarding their reliability especially at low levels of recirculation. New methods have shown that the majority of patients have much less recirculation than previously suspected. However, some of these methods are prone to the same factors that limit BUN measurement accuracy. A new method, ultrasound dilution, was studied that avoids these problems and supports a new clinical reality--zero access recirculation. Information on the relationship of recirculation to access flow was also obtained which supports the assumption that patients with adequate vascular access flows have no recirculation.

In vivo measurement of hemodialyzer fiber bundle volume: theory and validation.

BACKGROUND: Fiber bundle volume (FBV), the space within the blood compartment of hollow fiber dialyzers, may decrease during treatment due to clotting. The clots may be flushed out of the dialyzer prior to measurements of FBV by dialyzer reprocessing equipment and a significant drop in FBV during the session may go unrecognized. METHODS: FBV was measured (1) from the transit time of a saline bolus passing through the dialyzer as recorded by ultrasound dilution sensors placed on the arterial and venous blood lines; (2) from the change in blood concentration induced by a step change in the rate of ultrafiltration as recorded by the venous sensor. RESULTS: In vitro FBV ranged from 47 to 121 ml. Paired absolute differences between the ultrasound and volumetric measurements (flushing saline out of the dialyzer into a graduated cylinder) were 0.16 +/- 4.23% (N = 42) and 2.10 +/- 7.26% (N = 13) for the bolus and ultrafiltration methods, respectively. In vivo reproducibility of the bolus and ultrafiltration methods were 2.65 +/- 2.11% (N = 122) and 3.79 +/- 3.93% (N = 32), respectively. During 31 treatments the FBV by dilution showed an average decrease of 4.17 +/- 8.60%, and in 6 cases FBV fell more than 10%, while measurements of the same FBV by reuse equipment showed an increase of 0.99 +/- 5.82%, P < 0.01. CONCLUSIONS: FBV measured by the dilution methods was accurate and reproducible. Preliminary results suggest that in vivo FBV may differ significantly from results reported by reprocessing machines.