Stanley Frinak

Detecting Vascular Access Dysfunction

Access flow (QACC) is a major determinant of patency. Access recirculation (AR > 2%), normalized venous intra-access pressure (vPIA/MAP), and QACC are used to detect access dysfunction. We compared these three measures of access function (ultrasound dilution to measure AR and QACC). A total of 779 measurements were performed on 58 arteriovenous fistulas (AVFs) and 114 polytetrafluoroethylene (PTFE) grafts (1–8/access) over 13 months, and the access parameters at the beginning of each period were related to access events within that period. Pump blood flow averaged >420 ml/min. AR occurred uncommonly (3.8%), and in half the cases, resulted from technical error by staff. In accesses that thrombosed or underwent intervention for stenosis, AR was present in only 3 of 11 AVFs and 8 of 57 PTFE accesses. When AR was present in grafts, QACC averaged 270 ± 23, and access thrombosis followed unless intervention occurred. In grafts, vPIA/MAP averaged 0.34 ± 0.01 in those remaining patent, 0.52 ± 0.08 in those that had undergone intervention, and 0.54 ± 0.04 in those that had thrombosed. QACC averaged 1,121 ± 26,605 ± 45, and 550 ± 65 ml/min, respectively, in the three groups. By contrast, QACC differed significantly in patent AVFs (1,053 ± 35) compared with failing AVFs (363 ± 48), but vPIA/MAP did not. AR is thus a late manifestation of access failure. QACC is the best diagnostic test of access dysfunction in AVFs. Interpretation of vPIA/MAP in grafts is enhanced by periodic QACC measurements.

Detection of access strictures and outlet stenoses in vascular accesses. Which test is best

The location of stenoses within an access may influence the diagnostic value of access monitoring tests. Whereas decreasing access flow (QACC) should occur with both venous outlet stenoses and strictures within the body of the access, normalized intra-access venous pressure (vPIA/MAP) depends on location of the venous needle relative to the lesion. The authors determined the value of vPIA/MAP and direct measurement of percent access recirculation (AR) and QACC in detecting venous outlet stenoses and strictures. Abnormal access studies were evaluated by Doppler ultrasound and fistulography. Well functioning grafts and arteriovenous fistulas (AVFs) have no AR; QACC averages 1,101 ± 26 and 1,073 ± 35 ml/min, and vPIA/MAP ratios are 0.34 and 0.16, respectively. Venous

Failure of Standard Cardioplegic Techniques to Protect the Conducting System

To determine the site of persistent electrical activity during cardioplegic arrest, microelectrodes that were also capable of recording temperature were placed along the conducting system in dogs undergoing one hour of cardioplegic arrest. Electrical activity was highest in the atrioventricular (AV) junction area (AV node and proximal bundle of His), and the temperature in this area could not be lowered to the level of the temperature in the left ventricular apex by routine cardioplegic technique. Neither changing K+ concentration (16 to 20 mEq/L) nor adding procaine hydrochloride abolished the activity of the conducting system during cardioplegia, and only 2 of 15 dogs were in sinus rhythm 30 minutes after reperfusion. When the conducting system temperatures were lowered to less than 15 degrees C by right AV lavage with iced saline solution, electrical activity was abolished during arrest and all 4 of 4 animals were in sinus rhythm 30 minutes after reperfusion. This study localizes the site of persistent conducting system activity during cardioplegic arrest, confirms it can be abolished with local cooling, and establishes the relationship between conducting system activity during cardioplegia and the incidence of conduction block and junctional rhythm following reperfusion.

Hemoglobin Variability and Hyporesponsiveness: Much Ado About Something or Nothing?

Hemoglobin (Hb) variability is considered a discrete clinical entity that when present may presage poor clinical outcomes. However, Hb variability is an intrinsic property of biological systems and is present in all patients, those with and without the anemia of chronic kidney disease. Taken together, variability actually represents the integration of multiple influences at multiple levels in the life of a red cell, namely the summation of positive and negative influences on erythropoiesis. Thus, Hb variability may be interpreted as a mathematic function of time and is the result of a host of influences including definition of the normal Hb range, native erythron responsiveness/hyporesponsiveness, temporal changes in endogenous and exogenous erythropoiesis-stimulating agent (ESA) levels, the algorithms used to dose ESAs and their duration of action, the presence of biologically available iron, red cell turnover, and recyclable and non-recyclable blood loss and gain. When viewed within this construct of matrixed determinants, the source of hemoglobin variability is more readily identified. When variability is present but the etiology is not easily discerned, erythropoietic hyporesponsiveness must be considered and evaluated. Finally, integration of all of these concepts is possible within the context of an anemia management protocol.

Automated Intravascular Access Pressure Surveillance Reduces Thrombosis Rates

Although monitoring of vascular accesses by physical examination is nearly as sensitive as surveillance measurements by vascular access pressure when performed by examiners, the frequency of examinations is limited by time. We developed intravascular access pressure surveillance as a surrogate to physical examination. Using real‐time data from hemodialysis machines, we derived intravascular access pressure ratios for each dialytic procedure. An automated, noninvasive surveillance algorithm that generated a “warning” list of patients at risk for thrombosis was formulated. We hypothesized that this algorithm would reduce access thrombosis frequency. We designed a study comparing thrombosis rates during a baseline 6‐month interval to three subsequent 6‐month periods of active surveillance. Referrals for interventions during this 18‐month period were based on persistently abnormal elevated vascular access pressure ratio tests (VAPRT) >0.55. Thrombosis rates declined progressively for arteriovenous grafts (AVG) during the intervention period compared with the baseline period. Arteriovenous fistula (AVF) thrombosis rates decreased during postintervention months 13–18 during employment of the VAPRT. We conclude that use of VAPRT can reduce thrombosis rates in vascular accesses, and the magnitude of the effect is larger and more consistent in arteriovenous grafts (AVGs) than autologous AVFs.

In vivo 31‐P NMR of photoactivated hematoporphyrin derivative in cat brain

In vivo 31-P nuclear magnetic resonance (NMR) spectroscopy was performed on cat brains injected with hematoporphyrin derivative (HpD). A 2-cm-diam region of the right parietal lobe was photoactivated with red light. The 31-P NMR spectra of the photoactivated hemisphere revealed increased inorganic phosphate and decreased phosphocreatine and adenosine triphosphate (ATP) levels, compared to spectra obtained from the control hemisphere. In the absence of drug, no difference in spectra was observed between the photoradiated and control lobes. Our studies suggest that in vivo 31-P NMR spectroscopy may be used to monitor the effects of phototherapy on tissue high-energy phosphate metabolism.

Development of an online citrate/Ca2+ sensing system for dialysis

An online citrate and Ca(2+) sensing system based on sequential injection analysis (SIA) is developed as a safety module for hemodialysis. Host 1 displays high affinity towards citrate, and was selected for this study owing to its unique structural features. The o-aminomethylphenylboronic moiety can effectively interact with the α-hydroxycarboxylate moiety of citrate and the remaining two guanidiniums may further stabilize the complex via hydrogen bonds. Fura-2 chelates to Ca(2+) with a high selectivity and affinity and was utilized in this study for Ca(2+) measurements. The citrate sensing chemistry via an indicator displacement assay is orthogonal to the Ca(2+) sensing chemistry, and the use of sophisticated chemometrics is not required for data analysis. The citrate and Ca(2+) concentrations in dialysate samples are measured with the developed SIA system. The obtained citrate concentrations were verified via a commercially available enzymatic assay and an NMR method, respectively, while the Ca(2+) concentrations were verified via atomic absorption.

Increased urea kinetic modeling volume. Possible mechanisms and its significance.

The predence of access recirculation reduces delivered urea clearance and produces an increased volume/weight (V/M) ratio in three-point kinetic modeling. We measured nR in 20 patients receiving conventional hemodialysis and correlated results with normalized intra-access venous pressure (P1A) and with angiographic or color-flow Doppler studies. Twenty patients were equally divided into those with and without persistently elevated modeled V/W ratios (0.64 vs 0.53), and subdivided into those with native and synthetic bridge graft accesses, Kinetic modeling parameters (Kt/V) and P1A did not difer between the two V/W groups. Modeled volume was quite accurately predicted by the equations in the normal group but deviated by 7.3 ±2.1 L in the high V/W ratio group. Three of 10 native and 4 of 10 graft accesses had trivial and hemodynamically insignificant abnormalities by colourflow Doppler or angiography. Recirculation was independent of V/W group and when measured by the slow flow/clamp technique was negligible (<2.0%). Access flow always exceded prescrivbed dialyzer blood flow by more than 300 ml/min. Therefore, access recirculation was unlikely. In many of the high V/W patients, alternative explanations for falsely high modeled volume were found on follow-up modeling. Only one patient appeared to have a true high volume. The authors conclude that high urea volumes during kinetic modeling are unlikely to occur from access recirculation, but arise from other factors affecting the delivered urea clearance.