Hemodialysis Vascular Access: A Historical Perspective on Access Promotion, Barriers, and Lessons for the Future.

This review describes the history of vascular access for hemodialysis (HD) over the past 8 decades. Reliable, repeatable vascular access for outpatient HD began in the 1960s with the Quinton-Scribner shunt. This was followed by the autologous Brecia-Cimino radial-cephalic arteriovenous fistula (AVF), which dominated HD vascular access for the next 20 years. Delayed referral and the requirement of 1.5-3 months for AVF maturation led to the development of and increasing dependence on synthetic arteriovenous grafts (AVGs) and tunneled central venous catheters, both of which have higher thrombosis and infection risks than AVFs. The use of AVGs and tunneled central venous catheters increased progressively to the point that, in 1997, the first evidence-based clinical practice guidelines for HD vascular access recommended that they only be used if a functioning AVF could not be established. Efforts to promote AVF use in the United States during the past 2 decades doubled their prevalence; however, recent practice guidelines acknowledge that not all patients receiving HD are ideally suited for an AVF. Nonetheless, improved referral for AVF placement before dialysis initiation and improved conversion of failing AVGs to AVFs may increase AVF use among patients in whom they are appropriate.

Remote Monitoring of Sustained Low-Efficiency Dialysis (SLED) Machines in Intensive Care Unit.

The Henry Ford Health System provides patients with a safe, improved system of continuous kidney replacement therapy using a proprietary, 24-hour sustained low-efficiency dialysis (SLED). The SLED system utilizes regional citrate anticoagulation (RCA) in conventional hemodialysis machines that have been configured to provide slow dialytic therapy. Within our hospital complex, SLED-RCA systems are deployed in intensive care units distributed over 4 floors in 2 buildings. This widespread footprint represents a spatial challenge for hemodialysis technicians. Fifteen SLED-RCA machines may be running at one time, and each deployed unit may signal an alarm for multiple reasons. Previously, audible alarms prompted intensive care unit nurses to identify the alarming machine and manually notify technicians by telephone. Technicians would then travel to resolve the alarm. To improve the process of addressing SLED-RCA machine alarms, we developed a remote alert alarm system that wirelessly notifies hemodialysis technicians of specific machine alarms. A quality improvement analysis of nearly 1,000 SLED-RCA alarms over a 1-week period revealed that the average time for alarm correction with a remote alert alarm system was approximately 5 minutes. Reducing alarm resolution time may free technicians and nurses for other critical duties.

Sodium-based osmotherapy for hyponatremia in acute decompensated heart failure.

Acute decompensated heart failure (ADHF) accounts for more than 1 million hospital admissions annually and is associated with high morbidity and mortality. Decongestion with removal of increased total body sodium and total body water are goals of treatment. Acute kidney injury (AKI) or chronic kidney disease (CKD) is present in two-thirds of patients with ADHF. The pathophysiology of ADHF and AKI is bidirectional and synergistic. AKI and CKD complicate the management of ADHF by decreasing diuretic efficiency and excretion of sodium and water. Among patients hospitalized with ADHF, hyponatremia is the most common electrolyte abnormality and is classically encountered with volume overload. ADHF represents an additional therapeutic challenge particularly when oligoanuria is present. Predilution continuous venovenous hemofiltration with sodium-based osmotherapy can safely increase plasma sodium concentration without deleteriously increasing total body sodium. We present a detailed methodology that addresses the issue of hypervolemic hyponatremia in patients with ADHF and AKI.

Sodium-Based Osmotherapy in Continuous Renal Replacement Therapy: a Mathematical Approach.

Cerebral edema, in a variety of circumstances, may be accompanied by states of hyponatremia. The threat of brain injury from hypotonic stress-induced astrocyte demyelination is more common when vulnerable patients with hyponatremia who have end stage liver disease, traumatic brain injury, heart failure, or other conditions undergo overly rapid correction of hyponatremia. These scenarios, in the context of declining urinary output from CKD and/or AKI, may require controlled elevations of plasma tonicity vis-à-vis increases of the plasma sodium concentration. We offer a strategic solution to this problem via sodium-based osmotherapy applied through a conventional continuous RRT modality: predilution continuous venovenous hemofiltration.

Sensors and hybrid therapies: a new approach with automated citrate anticoagulation.

BACKGROUND: Hybrid therapies use intermittent hemodialysis (IHD) machines adapted to provide prolonged intermittent or continuous renal replacement therapy in the intensive care unit (ICU). Despite the low cost, hybrid therapy use is limited warranting a novel approach. METHODS: The literature was reviewed for limitations of hybrid protocols, use of regional citrate anticoagulation (RCA) on hybrid systems and sensors for IHD and hybrid therapy. The novel hybrid program in the authors' institution is presented as a plausible future direction for the modality. RESULTS: Hybrid therapies are limited by access flow and clotting alarms. Technology limitations render many IHD sensors inoperable at low dialysate flow. A synergy with RCA allows a novel, safe approach with low blood flows and high dialysate flows with alarm- and clotting-free operation and all commercial IHD sensors functional. CONCLUSION: The low cost, ease of use, safety and efficacy of hybrid therapy with near-automated RCA may lead to rapid expansion of this form of ICU renal support.

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.

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.

Automated regional citrate anticoagulation: technological barriers and possible solutions.

BACKGROUND: Large-scale adoption of regional citrate anticoagulation (RCA) is prevented by risks of the technique as practiced traditionally. Safe RCA protocols with automated delivery on customized dialysis systems are needed. METHODS: We applied kinetic analysis of solute fluxes during RCA to design a protocol for sustained low-efficiency dialysis (SLED) for critically ill patients. We used a high-flux hemodialyzer, a zero-calcium (Ca) dialysate, a dialysis machine with online clearance and access recirculation monitoring, and a separate optical hematocrit (Hct) sensor. Flow rates were Q(B) = 200 ml/min for blood; Q(D) = 400 ml/min for dialysate, with Na = 140 mmol/l and HCO(3) = 32 mmol/l; Q(citrate) = 400 ml/h of acid citrate dextrose A; ultrafiltration as indicated. The Q(Ca) was infused into the return blood line, adjusted hourly based on online Hct and a <24-hour-old albumin level. RESULTS: Using the SLED-RCA protocol in an anhepatic, ex vivo dialysis system, ionized Ca (iCa) was >1 mmol/l in the blood reservoir and <0.3 mmol/l in the blood circuit after citrate but before Ca infusion (Q(Ca)) with normal electrolyte composition of the blood returning to the reservoir. Clinically, SLED-RCA completely abrogated clotting, without adverse electrolyte effects. The Q(Ca) prediction algorithm maintained normal systemic iCa (0.95-1.4 mmol/l) in all patients. The high citrate extraction on the dialyzer prevented systemic citrate accumulation even in shock liver patients. Safety analysis shows that building a dialysis system for automated SLED-RCA is feasible. CONCLUSION: Using predictive Q(Ca) dosing and integrating control of the infusion pumps with the dialysis machine, SLED-RCA can be near-automated today to provide a user-friendly and safe system.

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.

What is so bad about a hemoglobin level of 12 to 13 g/dL for chronic kidney disease patients anyway?

Randomized controlled trials (RCTs) clearly indicate a possible cardiovascular morbidity and mortality risk when deliberately targeting a normal hemoglobin (Hb) concentration of 13 to 15 g/dL. By contrast, observational studies point to greater hospitalization and mortality at Hb levels <11 g/dL. There are no direct data to help us determine where, within this broad range, the optimal Hb lies. In RCTs and observational studies, significant confounding from the interrelationships of anemia and epoetin resistance occurs in patients with a serious illness. Patients with comorbidities such as malnutrition and inflammatory processes are more resistant to epoetin and, invariably, require greater cumulative epoetin doses. The effect of a higher erythropoiesis-stimulating agent (ESA) dose on increasing mortality has been noted repeatedly in post hoc analyses of RCTs. It is therefore too simplistic to solely attribute the outcomes achieved in RCTs to "target Hb." We discuss various mechanisms for potential harm at higher Hb levels as opposed to those that may be obtained from higher epoetin doses. For the individual patient, the therapeutic decision should center on what Hb is most appropriate at a "safe" ESA dose. Consequently, an Hb of 12 to 13 g/dL may be totally appropriate in some patient populations.

Effect of differing blood lines on delivered blood flow during hemodialysis.

UNLABELLED: BACKGROUND The influence of differing blood tubing sets on delivered dialyzer blood flow (Q B ) was studied using ReadySet (RS; Medisystem Inc, Seattle, WA) and CombiSet (CS; Fresenius, Walnut Creek, CA). METHODS: In vitro, we measured Q B and pre-pump arterial pressures (P A; in millimeters of mercury) during 4 hours at a prescribed blood pump flow (Q P ) of 450 mL/min, using a glycerin-water mixture for RS and CS blood tubing sets (n = 10 each). We then performed 3 clinical studies to determine the difference between Q P and Q B as a function of P A for both tubing types and any effects of tubing type on delivered Kt/V in patients. RESULTS: In vitro, 4-hour time-averaged Q B was 451 mL/min with RS versus 422 mL/min with CS. Q B was approximately 40 mL/min greater using RS than CS blood tubing sets at Q P of approximately 445 mL/min with [Q P - Q B ] increasing linearly with P A for CS, but not RS (study 1). At a mean Q P of approximately 408 mL/min, CS blood tubing significantly increased Kt/V by approximately 0.1 (90 patients; study 2). In study 3, [Q P - Q B ] increased with treatment time with CS (8 to 29 mL/min), but not RS (from -4 to 6 mL/min). For patients achieving equal Q P of 400 mL/min or greater for all treatments (n = 11), paired analysis showed greater values for urea reduction ratio (+3.5%; P = 0.039) and Kt/V (+0.14; P = 0.04) with RS than CS tubing sets. CONCLUSION: Differences in [Q P - Q B ] occur both in vitro and in vivo, are much smaller with RS than CS tubing sets, and result in a greater delivered Kt/V of up to 0.14 for RS.

Prevention of hemodialysis-related muscle cramps by intradialytic use of sequential compression devices: a report of four cases.

BACKGROUND: Hemodialysis (HD)-related lower extremity (LE) muscle cramps are a common cause of morbidity in end-stage renal disease patients on maintenance HD. Numerous pharmacologic and physical measures have been tried with variable success rates. METHODS: Sequential compression devices (SCD) improve venous return (VR) and are commonly used to prevent LE deep venous thrombosis in hospitals. We hypothesized that LE cramps are triggered by stagnant venous flow during HD and are preventable by improving VR. We prospectively studied four adult patients (mean age 61 +/- 14 years) on thrice-weekly HD who experienced two or more episodes of LE cramping weekly in the month before the study. SCD were applied before each HD on both legs and compressions were intermittently applied at 40 mmHg during treatment. RESULTS: All four patients reported complete resolution of cramping during the study period that lasted 1 month or 12 consecutive dialysis treatments. CONCLUSION: Application of SCD to LE may prevent the generation of LE HD-related cramping in a select group of patients. Larger, controlled studies are needed to establish the utility of this noninvasive alternative for the prevention of LE HD-related cramps.

Dynamic venous access pressure ratio test for hemodialysis access monitoring.

BACKGROUND: Early recognition of arteriovenous graft (AVG) dysfunction in hemodialysis (HD) patients followed by prompt corrective procedures reduces AVG thrombosis rates and lengthens access survival. We developed a method to prospectively monitor AVGs that uses an algorithm to calculate venous access pressure (VAP) during HD from the venous drip chamber pressure (VDP). METHODS: Sham HD with blood was performed using standard blood tubing and a 1-in. 15-G needle. The pressure needed to overcome circuit resistance at an intra-access pressure of zero (VDP(0)) was recorded at blood flow rates (Q(b)s) from 0 to 600 mL/min and hematocrits varied in steps from 38.4% to 18.2%. An equation for VDP(0) was developed. VAP in patients was calculated as VAP = VDP - VDP(0). VAP ratio (VAPR) was defined as VAP/mean arterial pressure (MAP). VAPR was calculated only if MAP was greater than 75 mm Hg, Q(b) was greater than 200 mL/min, and VDP was greater than 20 mm Hg. A positive VAPR test (VAPRT) result was defined as three consecutive treatments with VAPR exceeding 0.55 during a given month. Sensitivity and specificity of VAPRT to predict a graft event, defined by AVG occlusion or requirement for angioplasty, were calculated. RESULTS: During a 3-month interval, 120 HD patients with AVGs underwent 359 VAPRTs while access outcomes were monitored for 6 months. After 3 months, sensitivity and specificity for detection of a graft event were 70% +/- 8% and 88% +/- 2% and increased to 74% +/- 5% and 92% +/- 3% at 6 months, respectively. CONCLUSION: The VAPRT is a valuable tool to prospectively monitor for adverse AVG events.

Optimization of epoetin therapy with intravenous iron therapy in hemodialysis patients.

Iron deficiency limits the efficacy of recombinant human erythropoietin (rhEPO) therapy in end-stage renal disease (ESRD) patients. Functional iron deficiency occurs with serum ferritin >500 ng/ml and/or transferrin saturation (TSAT) of 20 to 30%. This study examines the effects of a maintenance intravenous iron dextran (ivID) protocol that increased TSAT in ESRD hemodialysis patients from conventional levels of 20 to 30% (control group) to those of 30 to 50% (study group) for a period of 6 mo. Forty-two patients receiving chronic hemodialysis completed a 16- to 20-wk run-in period, during which maintenance ivID and rhEPO were administered in amounts to achieve average TSAT of 20 to 30% and baseline levels of hemoglobin of 9.5 to 12.0 g/dl. After the run-in period, 19 patients randomized to the control group received ivID doses of 25 to 150 mg/wk for 6 mo. Twenty-three patients randomized to the study group received four to six loading doses of ivID, 100 mg each, over a 2-wk period to achieve a TSAT >30% followed by 25 to 150 mg weekly to maintain TSAT between 30 and 50% for 6 mo. Both regimens were effective in maintaining targeted hemoglobin levels. Fifteen patients in the control group and 17 patients in the study group finished the study in which the primary outcome parameter by intention to treat analysis was the rhEPO dose needed to maintain prestudy hemoglobin levels. Maintenance ivID requirements in the study group increased from 176 to 501 mg/mo and were associated with a progressive increase in serum ferritin to 658 ng/ml. Epoetin dose requirements for the study group decreased by the third month and remained 40% lower than for the control group, resulting in an overall cost savings in managing the anemia. Secondary indicators of iron-deficient erythropoiesis were also assessed. Zinc protoporphyrin did not change in either group. Reticulocyte hemoglobin content increased only in the study group from 28.5 to 30.1 pg. It is concluded that maintenance of TSAT between 30 and 50% reduces rhEPO requirements significantly over a 6-mo period.