- Email: [email protected]
Analysis of variable flow doppler hemodialysis access flow measurements and comparison with ultrasound dilution
ORIGINAL INVESTIGATIONS
Analysis of Variable Flow Doppler Hemodialysis Access Flow Measurements and Comparison With Ultrasound Dilution William F. Weitzel, MD, Jonathan M. Rubin, MD, PhD, Sean F. Leavey, MD, Richard D. Swartz, MD, Rajnish K. Dhingra, MD, and Joseph M. Messana, MD ● The variable flow (VF) Doppler method determines access blood flow from the pump speed–induced change in Doppler signal between the arterial and venous needles. This study evaluated 35 patients in two analyses to assess VF Doppler measurement reproducibility (54 paired measurements) and compared VF Doppler and ultrasound dilution flow measurements (24 paired measurements). VF Doppler measurement variations were 4% for access flow less than 800 mL/min (n ⴝ 17), 6% for access flow of 801 to 1,600 mL/min (n ⴝ 22), and 11% for access flow greater than 1,600 mL/min (n ⴝ 15). The mean measurement coefficient of variation was 7% for VF Doppler compared with 5% for ultrasound dilution. Correlation coefficients (r) between VF Doppler and ultrasound dilution access flow measurements were 0.79 (n ⴝ 24; P < 0.0001), 0.84 for access flow less than 2,000 mL/min (n ⴝ 20; P < 0.0001), and 0.91 for access flow less than 1,600 mL/min (n ⴝ 18, P < 0.0001). VF Doppler measurements using indicated versus measured pump flow rates correlated highly (r ⴝ 0.99; P < 0.0001). VF Doppler therefore yields reproducible access volume flow measurements that correlate with ultrasound dilution measurements. The VF Doppler method is dependent on the pump-induced change in access Doppler signal and therefore is inherently most accurate and reproducible at lower access blood flow rates. This method appears capable of determining access flow rates in the clinically useful range. © 2001 by the National Kidney Foundation, Inc. INDEX WORDS: Hemodialysis (HD); access; graft; fistula; Doppler; volume flow; blood flow; access monitoring.
D
IALYSIS ACCESS remains a major cause of morbidity among dialysis patients and a frequent cause for hospitalization.1,2 The National Kidney Foundation-Dialysis Outcomes Quality Initiatives guidelines and many researchers and clinical professionals have advocated access surveillance as a means to improve patient care and reduce access-related costs.3-5 Appropriate access surveillance allows for timely corrective intervention, and monitoring has been shown to increase graft life and prevent thrombosis.4 By preventing access thrombosis, improved access surveillance may reduce morbidity and significantly enhance the quality of life of hemodialysis patients, as well as help control the $1 billion annual costs associated with access care in the United States.1-4,6 Several approaches have been developed to aid in access surveillance. These methods include duplex ultrasound techniques,6-9 static and dynamic access pressure monitoring,9-12 recirculation,13 and various indicator dilution techniques.14-19 It is known that decreasing access blood flow rate predicts progression of access stenoses, and definitive and timely intervention prevents thrombosis.3,6-8,18,20 Both duplex ultrasound and indicator dilution techniques determine access blood flow rate and are important
tools for hemodialysis access evaluation. However, both these methods have shortcomings that limit their utility for access surveillance. Duplex imaging is costly, labor intensive, and subject to operator-dependent error.21 Indicator dilution techniques are time consuming and require dialysis blood line reversal.14-19 A novel method that measures blood flow using a changing Doppler signal characteristic as a function of blood flow rate in the access during dialysis is being evaluated.21-23 This variable flow (VF) Doppler measurement procedure has several potential advantages. First, a small change in cross-sectional radius measurement leads to a large change in volume flow calculations by duplex because area varFrom the Departments of Internal Medicine and Radiology, University of Michigan School of Medicine, Ann Arbor, MI. Received February 12, 2001; accepted in revised form June 29, 2001. Address reprint requests to William F. Weitzel, MD, Division of Nephrology, Department of Internal Medicine, University of Michigan Medical Center, 3914 Taubman Center, Ann Arbor, Michigan 48109-0364. E-mail: [email protected] © 2001 by the National Kidney Foundation, Inc. 0272-6386/01/3805-0002$35.00/0 doi:10.1053/ajkd.2001.28577
American Journal of Kidney Diseases, Vol 38, No 5 (November), 2001: pp 935-940
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ies with the square of the radius. Because the VF Doppler method does not require area measurement, this potential source of error is eliminated. Second, the Doppler signal beam angle is a potential source of error in duplex flow calculations, requiring accurate knowledge of the angle to calculate the velocity required for duplex volume flow determination. Conversely, the VF Doppler method uses any Doppler signal proportional to volume flow and thereby corrects itself for Doppler beam-angle variance, making the measurement insensitive to this source of error provided the Doppler beam angle remains fixed during the VF Doppler measurement. Third, the Doppler signal used to calculate volume flow by this method changes more dramatically with variable pump speeds when an access has low volume flow, making this method inherently most accurate in patients with lower access flow rates who are at greater risk for access thrombosis. Fourth, unlike indicator dilution techniques, there is no indicator or blood line reversal. METHODS The change in access Doppler signal with variable dialysis pump rates can be used to determine the access blood flow rate. This method exploits the decreasing access blood flow within the access between the needles with standard two-needle placement in the access graft, with the arterial needle upstream from the venous (blood return) needle during dialysis as blood is pumped through the dialysis
circuit. The position of the Doppler probe for VF Doppler is shown in Fig 1, and the measurement method was outlined in detail in a previous study.21 Briefly, the access has two needles introduced into its lumen during dialysis; one needle for the removal of blood (arterial) to pass through the dialysis circuit and one needle for the return of blood (venous) to the circulation. The flow through the graft or fistula downstream (QR) from the arterial needle decreases as a function of the blood flow rate (QA) in the dialysis circuit (QB). To the extent that the net flow through the system does not change during dialysis, this flow rate through the portion of the access between the dialysis needles during dialysis (QR) follows the relationship QR ⫽ QA – QB. Doppler signal S is measured downstream from the arterial needle (QR) at various values for QB (ie, various dialysis blood pump speeds). A modeling function then is constructed for this signal F(QB) using measured values such that S ⫽ F(QB). This modeling function may take the form of any algebraic or numerical one-to-one function. In this application, because Doppler velocity (and Doppler signal uncorrected for transducer angle) is linearly related to volume flow, a linear regression modeling function was used. The X intercept for this linear regression function represents the point at which the Doppler signal S is zero and yields the value at which QR equals zero, and therefore at which QB ⫽ QA, determining access flow.21
Study Procedure The prototype device was fashioned using a personal computer–based spectral Doppler board and software (SPECS USA Inc, Sarasota, FL) that allows calculation and export of various spectral waveform parameters, including instantaneous mean and time-averaged mean Doppler signals, used for the VF Doppler method. This device was connected to a laptop computer for signal analysis. The SPECS Doppler board performs spectral analysis, sampling Doppler data at 100 times/s, and displays the spectral waveform and derived
Fig 1. Access volume flow (QA) can be determined from the relationship between the Doppler signal remaining downstream (QR) in the access as a function of the dialysis blood flow rate (QB).
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parameters needed to perform the measurement on the laptop computer. Spectral data and derived parameters were imported into a database programmed to perform real-time calculation of the X intercept of the linear regression line from the VF Doppler data, thus determining access blood flow. The correlation coefficient of this regression line also was measured to give an index of measurement reliability. Measurements with r2 greater than 0.9 are considered reliable. For this protocol, each VF Doppler measurement was performed during routine dialysis using data from four spectral Doppler waveforms: two waveforms collected at 100 mL/min and two waveforms collected at 400 mL/min. The prototype allows for visual examination of the spectral waveform and audio output; therefore, the Doppler transducer can be centered easily over the graft for the signal to be maximized for data collection. An 8-MHz disc-shaped (2.0-cm diameter ⫻ 0.4-cm thick) Doppler transducer was used to facilitate Doppler sampling between the needles.
Patients Thirty-five patients with prosthetic bridge grafts were studied at the University of Michigan Medical Center’s Outpatient Hemodialysis Facility (Ann Arbor, MI). Patients underwent dialysis using Fresenius 2008H (Fresenius Medical Care, Lexington, MA) and Cobe Century System 3 (Gambro Renal Care Products, Lakewood, CO) with 15 G dialysis needles. We tested the reproducibility of experimental measurements in 17 patients using the correlation between the first and second measurements and coefficient of variation between paired measurements. Paired measurements were subsequently collected in 13 of these patients to assess the impact of changing the probe position between measurements on recorded access flow measurement. We then measured access blood flow rates in 24 subjects (including 6 patients from the reproducibility study) with prosthetic grafts using VF Doppler and ultrasound indicator dilution (Transonics, Ithaca, NY) during the same dialysis treatment to compare these measurement techniques.
Data Analysis The correlation between paired measurements was sought using linear regression analysis. Intermeasurement variation was expressed as a percentage of coefficient of variation. Percentage of coefficient of variation is defined as the SD in access flow rates divided by mean access flow rate multiplied by 100. The lower the intermeasurement of percentage of coefficient of variation, the greater the reproducibility of the measurement. The mean coefficient of variation of paired VF Doppler measurements was compared in three measurement ranges of access flow: less than 800, 800 to 1,600, and greater than 1,600 mL/min. The coefficient of variation for ultrasound dilution also was measured as a reference value for the coefficient of variation in access flow measurement. The correlation between VF Doppler and ultrasound dilution was determined. Finally, the indicated pump rate is often less than delivered pump rate at greater pump values depending on the degree of negative pressure generated at greater pump rates.24 We therefore retrospectively investigated the impact of this effect on VF Doppler measurement accuracy. We determined VF Doppler results
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using indicated versus measured pump speeds at indicated pump rates of 400 mL/min. Measured pump speeds were determined using the Transonics ultrasound dilution blood flow results, available for 22 patients.
RESULTS
The variation in VF Doppler measurements was 7% compared with 5% for ultrasound dilution (Table 1). Mean percentages of coefficient of variation of all paired VF Doppler measurements (n ⫽ 54) were compared in three measurement ranges of access flow: less than 800, 800 to 1,600, and greater than 1,600 mL/min. These values are listed in Table 1. The reproducibility of all VF Doppler measurements less than 2,000 mL/min is shown in Fig 2. The correlation coefficient (r) between repeated measurements with different probe positions was 0.93 (P ⬍ 0.001; n ⫽ 13). The comparison of VF Doppler and Transonics ultrasound dilution measurements is shown in Fig 3. The correlation coefficient (r) between VF Doppler and Transonics methods was 0.79 for all comparison measurements (n ⫽ 24; P ⬍ 0.0001). Correlation coefficients (r) between measurements were 0.91 for VF Doppler less than 1,600 mL/min (n ⫽ 18; P ⬍ 0.0001) and 0.84 for VF Doppler less than 2,000 mL/min (n ⫽ 20; P ⬍ 0.0001). The measured pump rate in our patients was 1.7 mL/min less than the indicated pump rate ⫾29 mL/min (7.3%) SD at an indicated pump rate of 400 mL/min. Although the difference between true and indicated pump rates may be most problematic in catheters with poor inflows rather than grafts or fistulae, it could conceivably influence the accuracy of the VF Doppler measurement. To investigate the impact of this effect Table 1. Measurement Coefficient of Variation for the Comparison Study Between VF Doppler and Ultrasound Dilution and All Paired VF Doppler Measurements Coefficient of No. of Variation (%) Measurements
Transonics (comparison study) VF Doppler (comparison study) VF Doppler (all) VF Doppler ⬍800 mL/min VF Doppler 800–1,600 mL/min VF Doppler ⬎1,600 mL/min
5 7 7 4 6 11
24 24 54 17 22 15
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Fig 2. Reproducibility of all VF Doppler measurements less than 2,000 mL/min (n ⴝ 44). Line of identity and correlation line are shown (r ⴝ 0.92; P < 0.0001).
on the VF Doppler measurement accuracy, we retrospectively redetermined VF Doppler results using both indicated and measured pump speeds when the dialysis machine indicated 400 mL/ min. The Transonics measured pump speed at 400 mL/min indicated pump speed had been stored for 22 of the 24 subjects. Because these results were determined retrospectively, we did not have pump measurements for 2 of the 24 patients studied. Figure 4 shows the comparison between VF Doppler results using indicated and measured pump rates. DISCUSSION
Early in the evaluation of this method, investigators encountered the relative inaccessibility of
Fig 3. VF Doppler and Transonics ultrasound dilution measurements with regression line and line of identity. Correlation coefficients (r ) are 0.79 for all comparison measurements (n ⴝ 24), 0.84 for VF Doppler less than 2,000 mL/min (n ⴝ 20), and 0.91 for VF Doppler less than 1,600 mL/min (n ⴝ 18).
Fig 4. Comparison of VF Doppler with indicated and measured pump rates. Line of identity and correlation line are shown. Correlation coefficient (r ) is 0.99 (P < 0.0001).
the patient’s graft for Doppler examination during dialysis because dialysis needles were taped during dialysis. This problem has largely been solved with suitable transducer selection and orientation. Because imaging is not required, there are several suitable small Doppler transducers that can be positioned between the needles for this measurement. One early solution was the use of a probe designed for urological applications (Urometrics Inc, St Paul, MN). This transducer was fit with a detachable strap fashioned by the investigators to secure it in place for measurements during dialysis. The transducer currently used is an 8-MHz, 60°, 0.4-cm thick by 2-cm diameter flat-disc transducer (SPECS USA Inc). This transducer fits in low profile, often under the venous dialysis tubing, between the needles oriented downstream along the access. There is no interference in the Doppler signal from the dialysis tubing even when the transducer and tubing are in direct contact. This transducer selection and orientation have made inaccessibility of the graft for VF Doppler examination an uncommon problem. However, further improvements in transducer ergonomics and beam profile are being investigated. Flow turbulence also has been raised as a potential problem. The palpable thrill and audible bruit are often attributed to access turbulence. Although turbulence may contribute to these physical findings, the thrill results from energy from the access blood flow being transmitted into the access wall, inducing palpable vibrations. These vibrations are seen in varying de-
VARIABLE FLOW DOPPLER ACCESS FLOW MEASUREMENTS
grees of intensity in the spectral Doppler signal and are often referred to as “wall clutter.” Although the Doppler signal intensity from the thrill may be high and the amplitude of the signal may be modulated with the cardiac cycle, the frequency observed is usually separate and lower than the Doppler signal from the access flow. In some cases, these low-frequency Doppler signals (from wall clutter) lower the instantaneous mean Doppler signal. However, data suggest that their contribution to the relative change in Doppler signal with pump speed used to calculate flow is not a significant limiting factor for this method. In addition, the spectral Doppler equipment being used (SPECS USA Inc) allows filtering of this low-frequency wall vibration, if necessary. Turbulence is a separate finding that requires additional investigation. The authors observed that laminar waveforms are predominately seen in prosthetic grafts (with or without access wall vibration). However, in the presence of turbulence, when there is net forward flux of blood through the access, Doppler velocity can be measured. Turbulence will increase the variance of the Doppler signal; ie, broaden the spectrum, but the mean should remain stable. When turbulence disappears, the mean should be relatively unchanged as long as the turbulence is superimposed on the average flux down the access. Spectral broadening and turbulent waveforms are seen more often in fistulae than grafts. Although this turbulence makes measurement more difficult in fistulae, the Doppler signal is influenced by pump speed in fistulae, evidenced by marked reversal of the Doppler flow signal when the access flow is less than the dialysis pump rate.25 Because thrombosis is less likely in fistulae than grafts, the value of this type of monitoring is more important for prosthetic grafts. However, we are performing additional studies to examine technical factors and limitations in determining accurate Doppler signals in fistulae and in the setting of turbulence. The ability to detect turbulence and measure other waveform characteristics related to the character of flow (spectral broadening, pulsatility, and resistive indices) within the graft using Doppler may prove to be a significant advantage of using Doppler-based technology to measure access flow. Low flow is an established risk factor for thrombosis. Differences in waveform
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character result from differences in graft geometry and may provide additional independent risk factors for thrombosis and markers of stenosis. Recent data25 suggest that a simple Doppler test for retrograde access flow on dialysis may be a specific predictor for access stenosis and more sensitive than access recirculation. However, checking for retrograde access flow with this method does not disrupt dialysis and takes only a few seconds to perform. Additional Doppler characteristics may increase the predictive value of surveillance when used in conjunction with flow measurements. This requires further study. In summary, VF Doppler yields reproducible access volume flow measurements that correlate with ultrasound dilution measurements in prosthetic grafts. The indicated dialysis pump rate yields reliable VF Doppler results when dialysis pump rates are 400 mL/min or less. In our facility, indicated pump rates at 400 mL/min were near measured pump rates and differed from measured pump rates by 7.3% (SD). The VF Doppler method appears capable of accurately determining access flow rates in the clinically useful range of less than 1,600 mL/min. Additional studies testing transducer design, signal processing, effects of turbulence, and clinical correlation are in progress to further examine this method of access evaluation. REFERENCES 1. Feldman HI, Held PJ, Hutchinson JT, Stoiber E, Hartigan MF, Berlin JA: Hemodialysis vascular access morbidity in the United States. Kidney Int 43:1091-1096, 1993 2. Mayers JD, Markell MS, Cohen LS, Hong J, Lundin P, Friedman EA: Vascular access surgery for maintenance hemodialysis: Variables in hospital stay. ASAIO J 38:113115, 1992 3. May RE, Himmelfarb J, Yenicesu M, Knights S, Ikizler TA, Schulman G, Hernanz-Schulman M, Shyr Y, Hakim RM: Predictive measures of vascular access thrombosis: A prospective study. Kidney Int 52:1656-1662, 1997 4. National Kidney Foundation: Clinical Practice Guidelines for Vascular Access. New York, NY, National Kidney Foundation, 1997; pp 35–42 5. US Renal Data System: X. The cost-effectiveness of alternative types of vascular access and the economic cost of ESRD. Am J Kidney Dis 26:S140-S156, 1995 (suppl 2) 6. Strauch BS, O’Connell RS, Geoly KL, Grundlehner M, Yakub YN, Teitjen DP: Forecasting thrombosis of vascular access with Doppler color flow imaging. Am J Kidney Dis 19:554-557, 1992 7. Findley DE, Longley DG, Foshager MC, Letourneau JG: Duplex and color sonography of hemodialysis arteriovenous fistulas and grafts. Radiographics 13:983-999, 1993
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8. Sands J: The role of color-flow Doppler ultrasound in the management of hemodialysis accesses. ASAIO J 44:4143, 1998 9. Sullivan KL, Besarab A, Bonn J, Shapiro MJ, Gardiner GA, Moritz MJ: Hemodynamics of failing dialysis grafts. Radiology 186:867-872, 1993 10. Besarab A, Sullivan KL, Ross RP, Moritz MJ: Utility of intra-access pressure monitoring in detecting and correcting venous outlet stenosis prior to thrombosis. Kidney Int 47:1364-1373, 1995 11. Besarab A, Frinak S: The prevention of access failure: Pressure monitoring. ASAIO J 44:35-37, 1998 12. Schwab SJ, Raymond JR, Saeed M, Newman GE, Dennis PA, Bollinger RR: Prevention of hemodialysis fistula thrombosis: Early detection of venous stenoses. Kidney Int 36:707-711, 1989 13. Besarab A, Sherman R: The relationship of recirculation to access blood flow. Am J Kidney Dis 29:223-229, 1997 14. Depner TA: Hemodialysis access: In-line methods. ASAIO J 44:38-39, 1998 15. Krivitski NM: Theory and validation of access flow measurement by dilution technique during hemodialysis. Kidney Int 48:244-250, 1995 16. Brosman PJ, Boereboom FTJ, Bakker CJ, Mali WPT, Eikelboom BC, Blankestijn PJ, Koomans HA: Access flow measurements in hemodialysis patients: In vivo validation of an ultrasound dilution technique. J Am Soc Nephrol 7:966-969, 1996 17. Lindsay RM, Bradfield E, Rothera C, Kianfar C,
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Malek P, Blake PG: A comparison of methods for the measurement of hemodialysis access recirculation and access blood flow rate. ASAIO J 44:62-67, 1998 18. Wang E, Schneditz D, Nepomuceno C, Lavarias V, Martin K, Morris AT, Levin NW: Predictive value of access blood flow in detecting access thrombosis. ASAIO J 44: M555-M558, 1998 19. Sands J, Glidden D, Miranda C: Hemodialysis access flow measurement. Comparison of ultrasound dilution and duplex ultrasonography. ASAIO J 42:M899-M901, 1996 20. Kirshbaum B, Compton A: Study of vascular access by angiodynography. Am J Kidney Dis 25:22-25, 1995 21. Weitzel WF, Rubin JM, Swartz RD, Woltmann DJ, Messana JM: Variable flow Doppler for hemodialysis access evaluation: Theory and clinical feasibility. ASAIO J 46:6569, 2000 22. Paun M, Beach K, Ahmad S, Hickman R, Meissner M, Plett C, Strandness E: New ultrasound approaches to dialysis access monitoring. Am J Kidney Dis 35:477-481, 2000 23. Keen M, Persig P, Gotch F: Non-invasive quantitive measurement of hemodialysis access graft (HG) flow. J Am Soc Nephrol 17:65A, 1985 (abstr 23) 24. Depner TA, Rizwan S, Sasi TA: Pressure effects on roller pump flow during hemodialysis. ASAIO Trans 31: M456-M459, 1990 25. Weitzel WF, Khosla N, Rubin JM: Retrograde hemodialysis access flow during dialysis as a predictor of access pathology. Am J Kidney Dis 37:1241-1246, 2001
Analysis of Variable Flow Doppler Hemodialysis Access Flow Measurements and Comparison With Ultrasound Dilution William F. Weitzel, MD, Jonathan M. Rubin, MD, PhD, Sean F. Leavey, MD, Richard D. Swartz, MD, Rajnish K. Dhingra, MD, and Joseph M. Messana, MD ● The variable flow (VF) Doppler method determines access blood flow from the pump speed–induced change in Doppler signal between the arterial and venous needles. This study evaluated 35 patients in two analyses to assess VF Doppler measurement reproducibility (54 paired measurements) and compared VF Doppler and ultrasound dilution flow measurements (24 paired measurements). VF Doppler measurement variations were 4% for access flow less than 800 mL/min (n ⴝ 17), 6% for access flow of 801 to 1,600 mL/min (n ⴝ 22), and 11% for access flow greater than 1,600 mL/min (n ⴝ 15). The mean measurement coefficient of variation was 7% for VF Doppler compared with 5% for ultrasound dilution. Correlation coefficients (r) between VF Doppler and ultrasound dilution access flow measurements were 0.79 (n ⴝ 24; P < 0.0001), 0.84 for access flow less than 2,000 mL/min (n ⴝ 20; P < 0.0001), and 0.91 for access flow less than 1,600 mL/min (n ⴝ 18, P < 0.0001). VF Doppler measurements using indicated versus measured pump flow rates correlated highly (r ⴝ 0.99; P < 0.0001). VF Doppler therefore yields reproducible access volume flow measurements that correlate with ultrasound dilution measurements. The VF Doppler method is dependent on the pump-induced change in access Doppler signal and therefore is inherently most accurate and reproducible at lower access blood flow rates. This method appears capable of determining access flow rates in the clinically useful range. © 2001 by the National Kidney Foundation, Inc. INDEX WORDS: Hemodialysis (HD); access; graft; fistula; Doppler; volume flow; blood flow; access monitoring.
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IALYSIS ACCESS remains a major cause of morbidity among dialysis patients and a frequent cause for hospitalization.1,2 The National Kidney Foundation-Dialysis Outcomes Quality Initiatives guidelines and many researchers and clinical professionals have advocated access surveillance as a means to improve patient care and reduce access-related costs.3-5 Appropriate access surveillance allows for timely corrective intervention, and monitoring has been shown to increase graft life and prevent thrombosis.4 By preventing access thrombosis, improved access surveillance may reduce morbidity and significantly enhance the quality of life of hemodialysis patients, as well as help control the $1 billion annual costs associated with access care in the United States.1-4,6 Several approaches have been developed to aid in access surveillance. These methods include duplex ultrasound techniques,6-9 static and dynamic access pressure monitoring,9-12 recirculation,13 and various indicator dilution techniques.14-19 It is known that decreasing access blood flow rate predicts progression of access stenoses, and definitive and timely intervention prevents thrombosis.3,6-8,18,20 Both duplex ultrasound and indicator dilution techniques determine access blood flow rate and are important
tools for hemodialysis access evaluation. However, both these methods have shortcomings that limit their utility for access surveillance. Duplex imaging is costly, labor intensive, and subject to operator-dependent error.21 Indicator dilution techniques are time consuming and require dialysis blood line reversal.14-19 A novel method that measures blood flow using a changing Doppler signal characteristic as a function of blood flow rate in the access during dialysis is being evaluated.21-23 This variable flow (VF) Doppler measurement procedure has several potential advantages. First, a small change in cross-sectional radius measurement leads to a large change in volume flow calculations by duplex because area varFrom the Departments of Internal Medicine and Radiology, University of Michigan School of Medicine, Ann Arbor, MI. Received February 12, 2001; accepted in revised form June 29, 2001. Address reprint requests to William F. Weitzel, MD, Division of Nephrology, Department of Internal Medicine, University of Michigan Medical Center, 3914 Taubman Center, Ann Arbor, Michigan 48109-0364. E-mail: [email protected] © 2001 by the National Kidney Foundation, Inc. 0272-6386/01/3805-0002$35.00/0 doi:10.1053/ajkd.2001.28577
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ies with the square of the radius. Because the VF Doppler method does not require area measurement, this potential source of error is eliminated. Second, the Doppler signal beam angle is a potential source of error in duplex flow calculations, requiring accurate knowledge of the angle to calculate the velocity required for duplex volume flow determination. Conversely, the VF Doppler method uses any Doppler signal proportional to volume flow and thereby corrects itself for Doppler beam-angle variance, making the measurement insensitive to this source of error provided the Doppler beam angle remains fixed during the VF Doppler measurement. Third, the Doppler signal used to calculate volume flow by this method changes more dramatically with variable pump speeds when an access has low volume flow, making this method inherently most accurate in patients with lower access flow rates who are at greater risk for access thrombosis. Fourth, unlike indicator dilution techniques, there is no indicator or blood line reversal. METHODS The change in access Doppler signal with variable dialysis pump rates can be used to determine the access blood flow rate. This method exploits the decreasing access blood flow within the access between the needles with standard two-needle placement in the access graft, with the arterial needle upstream from the venous (blood return) needle during dialysis as blood is pumped through the dialysis
circuit. The position of the Doppler probe for VF Doppler is shown in Fig 1, and the measurement method was outlined in detail in a previous study.21 Briefly, the access has two needles introduced into its lumen during dialysis; one needle for the removal of blood (arterial) to pass through the dialysis circuit and one needle for the return of blood (venous) to the circulation. The flow through the graft or fistula downstream (QR) from the arterial needle decreases as a function of the blood flow rate (QA) in the dialysis circuit (QB). To the extent that the net flow through the system does not change during dialysis, this flow rate through the portion of the access between the dialysis needles during dialysis (QR) follows the relationship QR ⫽ QA – QB. Doppler signal S is measured downstream from the arterial needle (QR) at various values for QB (ie, various dialysis blood pump speeds). A modeling function then is constructed for this signal F(QB) using measured values such that S ⫽ F(QB). This modeling function may take the form of any algebraic or numerical one-to-one function. In this application, because Doppler velocity (and Doppler signal uncorrected for transducer angle) is linearly related to volume flow, a linear regression modeling function was used. The X intercept for this linear regression function represents the point at which the Doppler signal S is zero and yields the value at which QR equals zero, and therefore at which QB ⫽ QA, determining access flow.21
Study Procedure The prototype device was fashioned using a personal computer–based spectral Doppler board and software (SPECS USA Inc, Sarasota, FL) that allows calculation and export of various spectral waveform parameters, including instantaneous mean and time-averaged mean Doppler signals, used for the VF Doppler method. This device was connected to a laptop computer for signal analysis. The SPECS Doppler board performs spectral analysis, sampling Doppler data at 100 times/s, and displays the spectral waveform and derived
Fig 1. Access volume flow (QA) can be determined from the relationship between the Doppler signal remaining downstream (QR) in the access as a function of the dialysis blood flow rate (QB).
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parameters needed to perform the measurement on the laptop computer. Spectral data and derived parameters were imported into a database programmed to perform real-time calculation of the X intercept of the linear regression line from the VF Doppler data, thus determining access blood flow. The correlation coefficient of this regression line also was measured to give an index of measurement reliability. Measurements with r2 greater than 0.9 are considered reliable. For this protocol, each VF Doppler measurement was performed during routine dialysis using data from four spectral Doppler waveforms: two waveforms collected at 100 mL/min and two waveforms collected at 400 mL/min. The prototype allows for visual examination of the spectral waveform and audio output; therefore, the Doppler transducer can be centered easily over the graft for the signal to be maximized for data collection. An 8-MHz disc-shaped (2.0-cm diameter ⫻ 0.4-cm thick) Doppler transducer was used to facilitate Doppler sampling between the needles.
Patients Thirty-five patients with prosthetic bridge grafts were studied at the University of Michigan Medical Center’s Outpatient Hemodialysis Facility (Ann Arbor, MI). Patients underwent dialysis using Fresenius 2008H (Fresenius Medical Care, Lexington, MA) and Cobe Century System 3 (Gambro Renal Care Products, Lakewood, CO) with 15 G dialysis needles. We tested the reproducibility of experimental measurements in 17 patients using the correlation between the first and second measurements and coefficient of variation between paired measurements. Paired measurements were subsequently collected in 13 of these patients to assess the impact of changing the probe position between measurements on recorded access flow measurement. We then measured access blood flow rates in 24 subjects (including 6 patients from the reproducibility study) with prosthetic grafts using VF Doppler and ultrasound indicator dilution (Transonics, Ithaca, NY) during the same dialysis treatment to compare these measurement techniques.
Data Analysis The correlation between paired measurements was sought using linear regression analysis. Intermeasurement variation was expressed as a percentage of coefficient of variation. Percentage of coefficient of variation is defined as the SD in access flow rates divided by mean access flow rate multiplied by 100. The lower the intermeasurement of percentage of coefficient of variation, the greater the reproducibility of the measurement. The mean coefficient of variation of paired VF Doppler measurements was compared in three measurement ranges of access flow: less than 800, 800 to 1,600, and greater than 1,600 mL/min. The coefficient of variation for ultrasound dilution also was measured as a reference value for the coefficient of variation in access flow measurement. The correlation between VF Doppler and ultrasound dilution was determined. Finally, the indicated pump rate is often less than delivered pump rate at greater pump values depending on the degree of negative pressure generated at greater pump rates.24 We therefore retrospectively investigated the impact of this effect on VF Doppler measurement accuracy. We determined VF Doppler results
937
using indicated versus measured pump speeds at indicated pump rates of 400 mL/min. Measured pump speeds were determined using the Transonics ultrasound dilution blood flow results, available for 22 patients.
RESULTS
The variation in VF Doppler measurements was 7% compared with 5% for ultrasound dilution (Table 1). Mean percentages of coefficient of variation of all paired VF Doppler measurements (n ⫽ 54) were compared in three measurement ranges of access flow: less than 800, 800 to 1,600, and greater than 1,600 mL/min. These values are listed in Table 1. The reproducibility of all VF Doppler measurements less than 2,000 mL/min is shown in Fig 2. The correlation coefficient (r) between repeated measurements with different probe positions was 0.93 (P ⬍ 0.001; n ⫽ 13). The comparison of VF Doppler and Transonics ultrasound dilution measurements is shown in Fig 3. The correlation coefficient (r) between VF Doppler and Transonics methods was 0.79 for all comparison measurements (n ⫽ 24; P ⬍ 0.0001). Correlation coefficients (r) between measurements were 0.91 for VF Doppler less than 1,600 mL/min (n ⫽ 18; P ⬍ 0.0001) and 0.84 for VF Doppler less than 2,000 mL/min (n ⫽ 20; P ⬍ 0.0001). The measured pump rate in our patients was 1.7 mL/min less than the indicated pump rate ⫾29 mL/min (7.3%) SD at an indicated pump rate of 400 mL/min. Although the difference between true and indicated pump rates may be most problematic in catheters with poor inflows rather than grafts or fistulae, it could conceivably influence the accuracy of the VF Doppler measurement. To investigate the impact of this effect Table 1. Measurement Coefficient of Variation for the Comparison Study Between VF Doppler and Ultrasound Dilution and All Paired VF Doppler Measurements Coefficient of No. of Variation (%) Measurements
Transonics (comparison study) VF Doppler (comparison study) VF Doppler (all) VF Doppler ⬍800 mL/min VF Doppler 800–1,600 mL/min VF Doppler ⬎1,600 mL/min
5 7 7 4 6 11
24 24 54 17 22 15
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Fig 2. Reproducibility of all VF Doppler measurements less than 2,000 mL/min (n ⴝ 44). Line of identity and correlation line are shown (r ⴝ 0.92; P < 0.0001).
on the VF Doppler measurement accuracy, we retrospectively redetermined VF Doppler results using both indicated and measured pump speeds when the dialysis machine indicated 400 mL/ min. The Transonics measured pump speed at 400 mL/min indicated pump speed had been stored for 22 of the 24 subjects. Because these results were determined retrospectively, we did not have pump measurements for 2 of the 24 patients studied. Figure 4 shows the comparison between VF Doppler results using indicated and measured pump rates. DISCUSSION
Early in the evaluation of this method, investigators encountered the relative inaccessibility of
Fig 3. VF Doppler and Transonics ultrasound dilution measurements with regression line and line of identity. Correlation coefficients (r ) are 0.79 for all comparison measurements (n ⴝ 24), 0.84 for VF Doppler less than 2,000 mL/min (n ⴝ 20), and 0.91 for VF Doppler less than 1,600 mL/min (n ⴝ 18).
Fig 4. Comparison of VF Doppler with indicated and measured pump rates. Line of identity and correlation line are shown. Correlation coefficient (r ) is 0.99 (P < 0.0001).
the patient’s graft for Doppler examination during dialysis because dialysis needles were taped during dialysis. This problem has largely been solved with suitable transducer selection and orientation. Because imaging is not required, there are several suitable small Doppler transducers that can be positioned between the needles for this measurement. One early solution was the use of a probe designed for urological applications (Urometrics Inc, St Paul, MN). This transducer was fit with a detachable strap fashioned by the investigators to secure it in place for measurements during dialysis. The transducer currently used is an 8-MHz, 60°, 0.4-cm thick by 2-cm diameter flat-disc transducer (SPECS USA Inc). This transducer fits in low profile, often under the venous dialysis tubing, between the needles oriented downstream along the access. There is no interference in the Doppler signal from the dialysis tubing even when the transducer and tubing are in direct contact. This transducer selection and orientation have made inaccessibility of the graft for VF Doppler examination an uncommon problem. However, further improvements in transducer ergonomics and beam profile are being investigated. Flow turbulence also has been raised as a potential problem. The palpable thrill and audible bruit are often attributed to access turbulence. Although turbulence may contribute to these physical findings, the thrill results from energy from the access blood flow being transmitted into the access wall, inducing palpable vibrations. These vibrations are seen in varying de-
VARIABLE FLOW DOPPLER ACCESS FLOW MEASUREMENTS
grees of intensity in the spectral Doppler signal and are often referred to as “wall clutter.” Although the Doppler signal intensity from the thrill may be high and the amplitude of the signal may be modulated with the cardiac cycle, the frequency observed is usually separate and lower than the Doppler signal from the access flow. In some cases, these low-frequency Doppler signals (from wall clutter) lower the instantaneous mean Doppler signal. However, data suggest that their contribution to the relative change in Doppler signal with pump speed used to calculate flow is not a significant limiting factor for this method. In addition, the spectral Doppler equipment being used (SPECS USA Inc) allows filtering of this low-frequency wall vibration, if necessary. Turbulence is a separate finding that requires additional investigation. The authors observed that laminar waveforms are predominately seen in prosthetic grafts (with or without access wall vibration). However, in the presence of turbulence, when there is net forward flux of blood through the access, Doppler velocity can be measured. Turbulence will increase the variance of the Doppler signal; ie, broaden the spectrum, but the mean should remain stable. When turbulence disappears, the mean should be relatively unchanged as long as the turbulence is superimposed on the average flux down the access. Spectral broadening and turbulent waveforms are seen more often in fistulae than grafts. Although this turbulence makes measurement more difficult in fistulae, the Doppler signal is influenced by pump speed in fistulae, evidenced by marked reversal of the Doppler flow signal when the access flow is less than the dialysis pump rate.25 Because thrombosis is less likely in fistulae than grafts, the value of this type of monitoring is more important for prosthetic grafts. However, we are performing additional studies to examine technical factors and limitations in determining accurate Doppler signals in fistulae and in the setting of turbulence. The ability to detect turbulence and measure other waveform characteristics related to the character of flow (spectral broadening, pulsatility, and resistive indices) within the graft using Doppler may prove to be a significant advantage of using Doppler-based technology to measure access flow. Low flow is an established risk factor for thrombosis. Differences in waveform
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character result from differences in graft geometry and may provide additional independent risk factors for thrombosis and markers of stenosis. Recent data25 suggest that a simple Doppler test for retrograde access flow on dialysis may be a specific predictor for access stenosis and more sensitive than access recirculation. However, checking for retrograde access flow with this method does not disrupt dialysis and takes only a few seconds to perform. Additional Doppler characteristics may increase the predictive value of surveillance when used in conjunction with flow measurements. This requires further study. In summary, VF Doppler yields reproducible access volume flow measurements that correlate with ultrasound dilution measurements in prosthetic grafts. The indicated dialysis pump rate yields reliable VF Doppler results when dialysis pump rates are 400 mL/min or less. In our facility, indicated pump rates at 400 mL/min were near measured pump rates and differed from measured pump rates by 7.3% (SD). The VF Doppler method appears capable of accurately determining access flow rates in the clinically useful range of less than 1,600 mL/min. Additional studies testing transducer design, signal processing, effects of turbulence, and clinical correlation are in progress to further examine this method of access evaluation. REFERENCES 1. Feldman HI, Held PJ, Hutchinson JT, Stoiber E, Hartigan MF, Berlin JA: Hemodialysis vascular access morbidity in the United States. Kidney Int 43:1091-1096, 1993 2. Mayers JD, Markell MS, Cohen LS, Hong J, Lundin P, Friedman EA: Vascular access surgery for maintenance hemodialysis: Variables in hospital stay. ASAIO J 38:113115, 1992 3. May RE, Himmelfarb J, Yenicesu M, Knights S, Ikizler TA, Schulman G, Hernanz-Schulman M, Shyr Y, Hakim RM: Predictive measures of vascular access thrombosis: A prospective study. Kidney Int 52:1656-1662, 1997 4. National Kidney Foundation: Clinical Practice Guidelines for Vascular Access. New York, NY, National Kidney Foundation, 1997; pp 35–42 5. US Renal Data System: X. The cost-effectiveness of alternative types of vascular access and the economic cost of ESRD. Am J Kidney Dis 26:S140-S156, 1995 (suppl 2) 6. Strauch BS, O’Connell RS, Geoly KL, Grundlehner M, Yakub YN, Teitjen DP: Forecasting thrombosis of vascular access with Doppler color flow imaging. Am J Kidney Dis 19:554-557, 1992 7. Findley DE, Longley DG, Foshager MC, Letourneau JG: Duplex and color sonography of hemodialysis arteriovenous fistulas and grafts. Radiographics 13:983-999, 1993
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8. Sands J: The role of color-flow Doppler ultrasound in the management of hemodialysis accesses. ASAIO J 44:4143, 1998 9. Sullivan KL, Besarab A, Bonn J, Shapiro MJ, Gardiner GA, Moritz MJ: Hemodynamics of failing dialysis grafts. Radiology 186:867-872, 1993 10. Besarab A, Sullivan KL, Ross RP, Moritz MJ: Utility of intra-access pressure monitoring in detecting and correcting venous outlet stenosis prior to thrombosis. Kidney Int 47:1364-1373, 1995 11. Besarab A, Frinak S: The prevention of access failure: Pressure monitoring. ASAIO J 44:35-37, 1998 12. Schwab SJ, Raymond JR, Saeed M, Newman GE, Dennis PA, Bollinger RR: Prevention of hemodialysis fistula thrombosis: Early detection of venous stenoses. Kidney Int 36:707-711, 1989 13. Besarab A, Sherman R: The relationship of recirculation to access blood flow. Am J Kidney Dis 29:223-229, 1997 14. Depner TA: Hemodialysis access: In-line methods. ASAIO J 44:38-39, 1998 15. Krivitski NM: Theory and validation of access flow measurement by dilution technique during hemodialysis. Kidney Int 48:244-250, 1995 16. Brosman PJ, Boereboom FTJ, Bakker CJ, Mali WPT, Eikelboom BC, Blankestijn PJ, Koomans HA: Access flow measurements in hemodialysis patients: In vivo validation of an ultrasound dilution technique. J Am Soc Nephrol 7:966-969, 1996 17. Lindsay RM, Bradfield E, Rothera C, Kianfar C,
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Malek P, Blake PG: A comparison of methods for the measurement of hemodialysis access recirculation and access blood flow rate. ASAIO J 44:62-67, 1998 18. Wang E, Schneditz D, Nepomuceno C, Lavarias V, Martin K, Morris AT, Levin NW: Predictive value of access blood flow in detecting access thrombosis. ASAIO J 44: M555-M558, 1998 19. Sands J, Glidden D, Miranda C: Hemodialysis access flow measurement. Comparison of ultrasound dilution and duplex ultrasonography. ASAIO J 42:M899-M901, 1996 20. Kirshbaum B, Compton A: Study of vascular access by angiodynography. Am J Kidney Dis 25:22-25, 1995 21. Weitzel WF, Rubin JM, Swartz RD, Woltmann DJ, Messana JM: Variable flow Doppler for hemodialysis access evaluation: Theory and clinical feasibility. ASAIO J 46:6569, 2000 22. Paun M, Beach K, Ahmad S, Hickman R, Meissner M, Plett C, Strandness E: New ultrasound approaches to dialysis access monitoring. Am J Kidney Dis 35:477-481, 2000 23. Keen M, Persig P, Gotch F: Non-invasive quantitive measurement of hemodialysis access graft (HG) flow. J Am Soc Nephrol 17:65A, 1985 (abstr 23) 24. Depner TA, Rizwan S, Sasi TA: Pressure effects on roller pump flow during hemodialysis. ASAIO Trans 31: M456-M459, 1990 25. Weitzel WF, Khosla N, Rubin JM: Retrograde hemodialysis access flow during dialysis as a predictor of access pathology. Am J Kidney Dis 37:1241-1246, 2001