Extracorporeal Blood Volume Research Articles

A model of hemodialysis after acute kidney injury in rats

BackgroundAcute kidney injury (AKI) is frequent among critically ill patients. Renal replacement therapy (RRT) is often required to deal with severe complications of AKI. This technique is however associated with side effects such as hemodynamic instability and delayed renal recovery. In this study, we aimed to describe a novel model of hemodialysis in rats with AKI and depict a dialysis membrane performance.MethodsEighteen Sprague–Dawley rats received 0.75% adenine-rich diet to induce AKI. After 2 weeks, nine underwent an arterio-venous extracorporeal circulation (ECC) (ECC group) for 2 h without a dialysis membrane on the circuit and nine received a hemodialysis session (HD group) for 2 h with an ECC circuit. All rats were hemodynamically monitored, and glomerular filtration rate (GFR) was measured by transcutaneous fluorescence after the injection of FITC-Sinistrin. Blood samples were collected at different time points to assess serum creatinine and serum urea concentrations and to determine the Kt/V. Sinistrin concentration was also quantified in both plasma and dialysis effluent.ResultsAfter 2 weeks of adenine-rich diet, rats exhibited a decrease in GFR. Both serum urea and serum creatinine concentrations increased in the ECC group but remained stable in the HD group. We found no significant difference in serum creatinine and serum urea concentrations between groups. At the end of experiments, mean serum urea was 36.7 mmol/l (95%CI 19.7–46.9 mmol/l) and 23.6 mmol/l (95%CI 15.2–33.5 mmol/l) in the ECC and HD groups, respectively (p = 0.15), and mean serum creatinine concentration was 158.0 µmol/l (95%CI 108.1–191.9 µmol/l) and 114.0 µmol/l (95%CI 90.2–140.9 µmol/l) in the ECC and HD groups, respectively (p = 0.11). The Kt/V of the model was estimated at 0.23. Sinistrin quantity in the ultrafiltrate raised steadily during the dialysis session. After 2 h, the median quantity was 149.2 µg (95% CI 99.7–250.3 µg).ConclusionsThis hemodialysis model is an acceptable compromise between the requirement of hemodynamic tolerance which implies reducing extracorporeal blood volume (using a small dialyzer) and the demonstration that diffusion of molecules through the membrane is achieved.

Outpatient Ultrafiltration to Prevent Hospital Readmission During Covid 19 Pandemic in Diuretic Intolerant Patient: Case Study

IntroductionHeart Failure (HF) is the leading cause of hospitalization among adults greater than 65 years of age in the U.S. and results in over 1,000,000 hospitalizations annually. Despite advances in medical therapeutics, mortality remains high. Adjustments in workflow across hospital systems have been instituted to reduce HF hospitalizations. Ambulatory HF clinics have helped in this regard. In the current COVID-19 pandemic, the need to minimize utilization of hospital resources and limit patient hospital admissions is paramount. Inpatient ultrafiltration (UF) has been utilized to improve congestion in patients with acute decompensated heart failure (ADHF). Less is known of outpatient utilization of UF in the ambulatory HF patient. We present a case of outpatient UF to reduce congestion in an ambulatory HF patient to minimize hospitalization in the era of COVID-19 pandemic.CaseA 70-year-old female with HF preserved ejection fraction, combined pre and post pulmonary capillary hypertension, with chronic dyspnea on continuous home oxygen, who presented to the HF clinic. The patient had previous multiple hospitalizations due to recurrent congestion, with therapies limited by dermatologic biopsy proven allergy to sulfa based diuretics. She had failed various diuretic regimens with recurrent desquamating whole body rash. She had recurrent weight gain during the COVID-19 pandemic, and again was refractory to outpatient therapies. Given her co-morbidities, she was deemed high risk for COVID-19 exposure. A decision to proceed with outpatient UF was made. The day of outpatient HF clinic visit, we placed a brachial dual lumen 16-gauge extended length catheter. A heparin drip was initiated thirty minutes prior to the start of UF per protocol. Baseline serum creatinine was 1.24 mg/dl and estimated GFR was 44. Initial outpatient session was performed over a total of 4-hours with isolated veno-venous UF utilizing the Aquadex Flex Flow system at a rate of 200 cc/hr fluid removal. The patient completed a total of 4 sessions, and total fluid removal was 4950mL. (Table 1) The patient had immediate improvement in symptoms.DiscussionUF is a method of decongestion that can be used as an alternative to loop diuretics. Simplified UF devices can utilize peripheral venous access, low blood flows, and small extracorporeal blood volume. Previous experience with intermittent outpatient UF utilizing peritoneal dialysis and hemofiltration has been reported, though not widely utilized. This is the first case to report the use of the Aquadex Flex Flow system to provide outpatient UF therapies in the COVID-19 era.ConclusionsPre-existing cardiac and pulmonary disease, including congestive HF, increase risk of serious complications from exposure to SARS-COVID-2 virus. We report a novel case of minimizing exposure risk of a congested HF patient using outpatient isolated veno-venous UF in the ambulatory setting.

Options in extracorporeal support of multiple organ failure

Multiorgan failure is among the most frequent reasons of death in critically ill patients. Based on extensive and long-term use of renal replacement therapy, extracorporeal organ support became available for other organ failures. Initially, most of these techniques (e.g. extracorporeal membrane oxygenation, extracorporeal CO2 removal [ECCO2R] and extracorporeal liver support) were used as stand-alone single organ support systems. Considering multiple interactions between native organs (“crosstalk”), combined or integrated extracorporeal organ support (ECOS) devices are intriguing. The concept of multiple organ support therapy (MOST) providing simultaneous and combined support for different failing organs was described more than 15 years ago by Ronco and Bellomo. This concept also implicates overcoming the “compartmentalized” approach provided by different single organ specialized professionals by a multidisciplinary and multiprofessional strategy. The idea of MOST is supported by the failure of several recent studies on single organ support including liver and lung support. Improvement of outcome by ECOS necessarily depends on optimized patient selection, integrated organ support and limitation of its side effects. This implicates challenges for engineers, industry and healthcare professionals. From a technical viewpoint, modular combination of pre-existing technologies such as renal replacement, albumin-dialysis, ECCO2R and potentially cytokine elimination can be considered as a first step. While this allows for stepwise and individual combination of standard organ support facilities, it carries the disadvantage of large extracorporeal blood volume and surfaces as well as additive costs. The more intriguing next step is an integrated platform providing the capacity of multiple organ support within one device. (This article is freely available.)

Lamictal® and Hemophagocytic Lymphohistiocytosis (HLH)

Introduction: Hemophagocytic lymphohisticoytosis (HLH) is a life threatening disorder resulting from uncontrolled macrophage activation. HLH may be primary or associated with active infection, autoimmune disorder or neoplasia. In a recently reported national surveillance report from the Food and Drug Administration (FDA), HLH was observed shortly after the initiation of lamotrigine (Lamictal®) in eight patients. We report the development and treatment of HLH in an otherwise healthy young woman who was briefly treated with lamotrigine. Case: A 27 year-old female with a history of bipolar depression and anxiety began treatment with lamotrigine 25 mg daily. Six days later, she experienced cough and odynophagia progressing to nausea, vomiting, and diarrhea over one day. She was treated with cephalexin for presumptive streptococcal pharyngitis by her primary physician. The next morning she developed diffuse rash, along with lethargy, myalgia, dyspnea and headache, and presented to the emergency room. Vital signs revealed tachycardia, tachypnea, hypoxia, and fever. Her exam was significant for decreased alertness, and pulmonary rhonchi with wheezing. A lumbar puncture displayed cerebrospinal fluid pleocytosis. Liver function tests were abnormal with elevated transaminases and hyperbilirubinemia, and ferritin was markedly elevated. In addition, serum creatinine, C-reactive protein, triglycerides and prothrombin time were elevated [Table]. Rash and overall rapid decline without clear etiology prompted concern for HLH. Lamotrigine was discontinued and a bone marrow biopsy was obtained and revealed normocellular marrow with relative myeloid hyperplasia with erythroid hypoplasia and increased histiocytes without evident hemophagocytosis. Our patient was initially treated with several broad spectrum antibiotics, including vancomycin, meropenem, acyclovir, and clindamycin. Due to worsening oxygenation and respiratory failure, she was intubated. Low-grade disseminated intravascular coagulation developed requiring two units of cryoprecipitate. Intravenous immunoglobulin G (1 gm/kg daily) was administered on hospital days 3 and 4 along with five days of pulse dose steroids (30 mg/kg). On hospital day 9, as her respiratory status worsened she was placed on venous-venous extracorporeal membrane oxygenation (VV ECMO). Treatment with etoposide (300 mg twice weekly - dose adjusted to account for extracorporeal blood volume) and dexamethasone (10 mg/m2 daily) per HLH protocol was initiated. Neutropenia developed after two doses of etoposide, and was subsequently held. The patient remained on VV ECMO for eight days, and was able to be extubated on hospital day 18. Liver and renal function improved, and ferritin level progressively declined over the course of the admission, to near normal at discharge [Figure]. She was discharged on hospital day 32 and is currently living independently at home. Discussion: Our patient was admitted with overwhelming illness, requiring intensive management. She met diagnostic criteria for HLHand once stable, was treated per guidelines of HLH-94 protocol. The month prior to her presentation, a report from investigators at the FDA (Kim T, et al, Neurology 2019;92 e2401-5) using the Adverse Event Reporting System described eight cases of HLH associated with lamotrigine. In light of this report, we describe another patient with HLH developing in a temporal relationship with lamotrigine and in absence of other identifiable causes. The patient was diagnosed with HLH based on H score probability of 94%. Similar to those cases in the FDA report, the syndrome developed shortly after starting lamotrigine and improved after stopping therapy. Lamotrigine is a widely prescribed for bipolar disorder, and increasingly for depression. Other adverse reactions associated with lamotrigine include Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms. It should be stated that these conditions cannot be excluded in this case, as they represent a similar over activation of the immune system with manifestations that overlap with HLH. Early identification and intervention are critical for the successful treatment of HLH. In addition to stopping lamotrigine, immunosuppressive therapy may be beneficial. Presently, there are no guidelines that specifically address treatment for drug-induced HLH. Disclosures No relevant conflicts of interest to declare.

Caloric Loss Associated with Apheresis

A common complaint attributed to apheresis is chill and hunger. Most likely this is a result of heat loss when blood is externalized from the body. This energy loss has not been quantitated. To determine caloric loss we monitored temperature loss using sterilized Omega hypodermic type K thermocouple probes inserted 20cm from the subject into the draw and return line, the centrifuge chamber, and the body. Inlet, return, centrifuge, and body temperature were recorded at one minute intervals using an Omega RDXL4SD Data Logger. Either a 38oC water bath (sham subject, n=2 per device) or rhesus macaque (weight 5-7 kg) undergoing apheresis served as subject. By definition one calorie (4.2 joules) is the amount of energy required to heat 1mL of water 1oC. By knowing that the heat capacity of blood is 3.6 joules/mL, we can calculate calorie loss per procedure. A total of 15 small volume apheresis procedures were performed with the Fenwal CS3000 on 12 rhesus macaques using a modified single small volume chamber procedure (Donahue et al., BLOOD 87:1644-53, 1996), 7 procedures were performed on 3 rhesus macaques using a Spectra Optia, and 6 procedures were performed on 3 rhesus macaques using a Fenwal Amicus device. Using water, the average temperature difference between inlet and return line dropped logarithmically (R2>0.89) for all three instruments as flow rate was increased (Fig. 1). Similarly the calorie loss/min logarithmically increased (R2>0.89) (Fig. 2) as flow rate increased. For CS3000 rhesus apheresis procedures, the drop in temperature between draw and return lines was 8.7(SD 1.5) oC at a flow rate of approximately 11mL/min, 9.5(0.9) oC for the Optia at a flow rate of 10mL/min, and 10.3(1.2) oC for the Amicus at a flow rate of 11mL/min. This drop was not significantly different between instruments (p=0.10). Procedures did differ in the amount of blood processed. For the CS3000, the blood volume processed per procedure (1013(18) mL) was significantly less (p<0.001) than either the Optia (1425(201) mL) or Amicus (1473(36) mL). In addition, centrifuge chamber temperature differed between the CS3000 (33.1(1.6) oC) and the Optia (28(1.9) oC) or Amicus (26.0(1.0)oC) (p<0.001) as the CS3000 has a chamber heating element. For the CS3000, calorie loss per procedure was 7712(1823) calories, for the Optia 11827(1987) calories, and the Amicus 13199(1354) calories. The significant difference (p<0.001) in caloric loss between the CS3000 and the other instruments was due to the larger blood volume processed using the Optia and Amicus. To prevent calorie loss we developed a method using a 50oC heated water bath in which a segment of the return line (38 cm or more) was placed in the water bath to equilibrate draw and return line temperatures without altering extracorporeal blood volume. On performing this procedure, we successfully matched draw and return line temperatures. This report documents for the first time caloric loss during apheresis procedures. In addition, it introduces a method to limit such a loss. Although adults >50kg may tolerate apheresis-associated caloric loss with only mild to moderate symptoms, pediatric patients, small animals, and debilitated and aging subjects, may not. Here we demonstrate the extent of calorie loss and a means to prevent it. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

We Lower Blood Flow for Intradialytic Hypotension.

Whether hemodialysis is performed through a fistula, graft, or a dialysis catheter, it is a common practice to lower the dialyzer blood flow in patients who develop intradialytic hypotension. Lowering dialyzer blood flow is assumed to reduce AV access blood flow and thus increase peripheral vascular resistance tending to raise blood pressure. As a general rule, however, such a reduction in dialyzer blood flow does not lower access flow; only in the case of an intra-access stenosis could this be the case. Reducing access blood flow (in both catheter and AV accesses) did ameliorate a number of potential contributors to intradialytic hypotension when older dialysis technologies were routinely used. A lower dialyzer blood flow reduced acetate influx, decreased extracorporeal blood volume, and decreased the release of vasodilatory products of blood-membrane interactions. However, none of these considerations are applicable to current dialysis practice.

Hemodialysis: Core Curriculum 2014

From the Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN. Received May 1, 2013. Accepted in revised form July 1, 2013. Originally published online November 21, 2013. Address correspondence to Thomas A. Golper, MD, S3303 Medical Center North, Vanderbilt University Medical Center, 21st Ave S, Nashville, TN 37232. E-mail: thomas.golper@vanderbilt. edu 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.07.028 PRINCIPLES OF DIALYSIS AND HOW MODALITIES DIFFER

Erythrocyte‐exchange with the OPTIA™ cell separator in patients with sickle‐cell disease

Erythrocyte-exchange (EEX) has proven to be a very useful tool in sickle-cell disease (SCD) patients either during acute painful crisis unresponsive to hydration and/or analgesia or as a prophylactic treatment in high risk patients in those who do not tolerate hydroxyurea (HU), with the aim of lowering HbS levels. EEX may be performed either by using continuous- or discontinuous flow devices, the former being of choice in children or in low-weight patients. Thus, a low extracorporeal blood volume (EBV) could allow for a better and safer procedure management. In this study we compared EEX procedure performed with the recently released OPTIA device with EEX procedures performed using the COBE Spectra device (EBV 185 vs 270 mL, respectively). Twenty-one EEX (4 as emergency treatment) were performed in 12 patients with the Spectra device and 25 (9 as emergency treatment) in 15 patients with the OPTIA device. All the procedures were well tolerated and uneventful. We did not observe significant differences between the two devices as to pre- and post-EEX parameters, namely in target hematocrit and in HbS reduction. Noteworthy, due to the lowest EBV allowed by the OPTIA device, an EEX procedure performed in a 13 Kg- child did not require a preliminary priming of the circuit. In conclusion, the OPTIA device proved to be as effective as the Spectra device in treating SCD patients either during sickling crisis or as prophylactic therapy. The OPTIA device can be safely used in the pediatric setting since it allows a lower EBV.

The Role of Early and Sufficient Isolated Venovenous Ultrafiltration in Heart Failure Patients With Pulmonary and Systemic Congestion

Hypervolemia, present in at least 70% of patients with decompensated heart failure, results in renal dysfunction due to increased renal venous pressure, impaired renal autoregulation, and decreased renal blood flow that are associated with increased morbidity and mortality. Loop diuretics, widely used in congested patients, result in the production of hypotonic urine and neurohormonal activation. In contrast, ultrafiltration (UF) removes isotonic fluid without increasing renin secretion by the macula densa. Simplified devices that permit us to perform UF with peripheral venous access, adjustable blood flows, and small extracorporeal blood volumes make this therapy feasible at most hospitals and in less acute care settings. Conflicting results on the effects of UF in heart failure patients underscore the challenges of patient selection and choice of fluid removal rates. Unfavorable outcomes in patients undergoing UF in the midst of cardiorenal syndrome type 1 are in contrast with the sustained benefits of UF initiated before unsuccessful use of high-dose intravenous (IV) diuretics. UF rates should be based on a precise knowledge of the degree of hypervolemia and careful assessment of blood volume changes, so that extracellular fluid gradually refills the intravascular space and volume depletion is avoided. Poor outcomes are likely to occur if fluid removal rates are not tailored to individual patients' clinical characteristics. A large trial is ongoing to determine if a strategy of early UF, initiated before renal function is worsened by other therapies, is superior to IV diuretics in reducing 90-day heart-failure-related hospitalizations in patients with pulmonary and systemic congestion.

Early-onset plasmapheresis and LDL-apheresis provide better disease control for pediatric homozygous familial hypercholesterolemia than HMG-CoA reductase inhibitors and ameliorate atherosclerosis

Plasmapheresis (PA) and low-density lipoprotein apheresis (LDL-A) were assessed in five children with homozygous familial hypercholesterolemia (HFH) previously receiving statins. LDL-A required smaller extracorporeal blood volumes. Mean HDL-cholesterol reduction post-procedure was 32% and 60% with LDL-A and PA, respectively. Non-HDL-C reduction was 64% and 69%, respectively. Pre-procedural LDL-C decreased significantly with weekly versus biweekly LDL-A. Carotid intimal media thickness (IMT) studies demonstrated disappearance of atheromatous lesions and normal ITM in 4/5 patients. Echocardiography revealed normal aortic valves, coronary orifices and supra-valvular area in all patients. Apheresis is effective in pediatric HFH. It may be started in patients weighing 14kg.

Photopheresis in pediatric patients with low‐body weight using the UVAR® XTS™ system

Photopheresis (ECP) with the UVAR XTS system has been limited to patients with a body weight > 40 kg, because extracorporeal blood volumes (ECV) may exceed 15% of the total blood volumes in low-body-weight patients. Because of these instrument characteristics, the use of ECP is limited in pediatric patients. In 5 patients (age 4 to 15 years) with graft-versus-host disease and with a body weight between 13 and 34 kilograms, photopheresis was performed using the UVAR XTS system. In 3 patients ECP could be performed by balancing the ECV with saline infusions. In 2 patients the system was modified in that the instrument was primed with packed red cells. During the treatment, fluid balance was guaranteed by a reservoir from a transfusion bag connected in parallel. Together 223 procedures were performed, among them 28 with the modification of the system. The treatments were well tolerated, and no episodes of hypotension were observed. It is possible to run ECP in low-body weight patients with the UVAR XTS system.

Acute Renal Failure and Renal Replacement Techniques

Acute renal failure (ARF) is a common event in critical patients usually taking place in a multiorganic failure context. This disorder implies a great clinical challenge. ARF could be defined as a sudden deterioration of the renal function that results in a loss of electrolyte, acid-base and fluid balance control, with subsequent accumulation of nitrogen wastes. Although ARF can appear in a wide range of pa- tients and conditions, its physiopathological bases is shared by most episodes with the hipoperfusion and/or renal ischemia as a triggering of the injury. Shock, and spe- cially septic shock is the main cause of ARF leading to renal replacement techniques. Though in the last twenty years continuous extracorporeal purification techniques have experienced an extraordinary growth, mortality remains high (50-70%). At pre- sent predominance of the continuous renal replacement therapy (CRRT) versus in- termittent hemodialysis (IHD) is based on its better hemodynamic stability, great ver- satility in the hydroelectrolytic handling, favored gaseous exchange and improvement of the ventricular filling pressures, low extracorporeal blood volume, smaller activa- tion of the complement, preferred elimination of fluids from the interstitial space, low rate of complications, control of uremia and the intravascular volume without protein or hydric restriction, possibility of elimination of certain toxics, good tolerance in pa- tients with intracranial hypertension and no need of specialized personnel. CRRT and related procedures are an effective and feasible treatment in patients with acute renal failure, severe cardiovascular instability, multisystem organ failure or politraumatized patients, being a simple and easy choice to implement and monitor. KEY WORDS—Acute renal failure. Continuous renal replacement therapy. Hemo- dialysis. Acute kidney injury. Renal replacement techniques.

Atrial natriuretic peptide serum concentration decreases in donors undergoing discontinuous plasmapheresis involving a large extracorporeal blood volume

In donor plasmapheresis, circulatory reactions occur at a similar frequency as in whole-blood donation although the large extracorporeal blood volume (ECV) occurring during discontinuous plasmapheresis might predispose donors to hypovolemic reactions. The regulatory mechanisms compensating for this intradonation blood volume (BV) deficit are not well understood. It was the aim of this study to delineate whether atrial natriuretic peptide (ANP) is involved in the BV regulation of plasmapheresis donors. Because ANP regulates volume overload, it might decrease during BV decrease in plasmapheresis. ANP serum concentrations were determined in 60 donors undergoing discontinuous plasmapheresis. Samples were taken before the start of the procedure and when maximum ECV (ECV(max)) was reached at the end of the last withdrawal. Donors were randomly selected after stratification for sex and BV. In a control investigation, the same donors were kept in a reclined position for the duration of a plasmapheresis session without plasma withdrawal. ANP plasma concentration changes were correlated with changes of hemodynamic variables, which were recorded noninvasively with bioelectrical impedance cardiography. Median ANP concentration decreased from 13.0 to 8.4 pg per mL during donation and from 11.6 to 10.5 pg per mL during the control session. The mean control-adjusted ANP change due to plasma withdrawal was -2.62 pg per mL (p = 0.006). This decrease was not attributable to a dilution effect. ANP change did not correlate with changes of recorded hemodynamic variables. The decrease of the ANP serum concentration during plasmapheresis demonstrates that the ECV(max) constitutes a hypovolemic challenge of the donors, which elicits a neurohormonal regulatory mechanism aimed at maintaining cardiovascular homeostasis.

Device and Technique for Extracorporeal Blood Volume Sequestration During Hemodialysis

We developed a technique for a controlled and reversible volume perturbation of the cardiovascular system during hemodialysis. The capacitance of the extracorporeal circulation was modified by an expansion bag, using separate filling and draining lines connected to postpump and prepump sections of the arterial line segment, respectively. The connection to this bag was manually operated by three-way valves. The volume sequestered into the blood bag was continuously measured by a weighing scale. Filling and draining of the expansion bag was measured in eight patients in two subsequent routine dialysis treatments. Four volume shifts were done in each treatment. Filling and draining rates and times depended on extracorporeal blood flow as well as arterial and venous line pressures. Bag inflow and outflow volumes were 215.8 +/- 28.5 ml/min and 221.6 +/- 37.0 ml/min, respectively. The total volume transiently sequestered in the bag was 479.8 +/- 61.3 ml. The duration of the whole test was 4.5 +/- 0.8 minutes. During filling, residual dialyzer blood flow was transiently reduced to 58.5 +/- 21.6 ml/min and the filtration fraction reached 30 +/- 13%. There were no adverse events such as clotting in the blood bag or in the dialyzer. The method provides rapid, reversible, and safe volume shifts between the patient and the extracorporeal circulation with the potential to elicit a hemodynamic response for characterizing the patient during each dialysis treatment.

Blood volume regulation in donors undergoing intermittent‐flow plasmapheresis involving a high extracorporeal blood volume

Intermittent-flow plasmapheresis (IFP) often involves a large extracorporeal blood volume (ECV) of donors during donation. Depending on equipment and donor characteristics, ECV can exceed 20 percent of a donor's blood volume (BV). It was the aim of this study to delineate mechanisms of BV regulation associated with these volume shifts. Parameters of BV regulation were recorded in 60 donors (30 men, 30 women) undergoing IFP, who were randomly selected after stratification for sex and BV. Shock index (SI), stroke volume (SV), cardiac index (CI), and thoracic fluid content (TFC) were determined at the beginning of the procedure and when maximum ECV (ECV(max)) was reached with noninvasive techniques. In a control investigation, donors were kept in reclined position for the duration of an IFP session without actually donating. SI increased significantly during IFP (+0.18; p < 0.0001). SV decreased significantly (-14.3 mL/stroke; p < 0.0001). CI did not decrease significantly (-0.07 L/min/m(2) body surface area; p = 0.33). Preservation of CI was due to a significant rise in heart rate (+13.4 beats/min; p < 0.0001). TFC decreased significantly during IFP (-0.77 kOmega(-1); p < 0.0001), indicating the development of an intravascular volume deficit. The changes of SI, heart rate, and TFC weakly correlated with ECV(max). The hemodynamic response during IFP is consistent with a hypovolemic challenge of the donors and is sufficient to maintain cardiac function. ECV(max) during donation does not reliably predict the degree of hypovolemic stress, as long as it remains below 20 percent. This might warrant reevaluation of collection limits based on ECV(max).

The role of ultrafiltration in the management of heart failure

In the United States, 90% of one million annual hospitalizations for heart failure are due to symptoms of volume overload. Hypervolemia contributes to heart failure progression and mortality. Treatment guidelines recommend that therapy for patients with heart failure be aimed at achieving euvolemia. Intravenous loop diuretics induce a rapid diuresis that reduces lung congestion and dyspnea. However, loop diuretics' effectiveness declines with repeated exposure. Unresolved congestion may contribute to high re-hospitalization rates. Furthermore, loop diuretics may be associated with increased morbidity and mortality due to deleterious effects on neurohormonal activation, electrolyte balance, and cardiac and renal function. Ultrafiltration is an alternative method of sodium and water removal, which safely improves hemodynamics in patients with heart failure. Application of this technology has been limited by the need for high flow rates, large extracorporeal blood volumes, and large-bore central venous catheters. A modified ultrafiltration device has overcome these limitations. Ultrafiltration may be a safe and effective alternative to intravenous diuretics in the treatment of decompensated heart failure.

Extracorporeal blood volume of donors during automated intermittent-flow plasmapheresis and its relevance to the prevention of circulatory reactions.

Intermittent-flow plasmapheresis often involves a large extracorporeal blood volume of the donor during the procedure with the concomitant risk of circulatory reactions. Guidelines governing donor recruitment often apply an arbitrary threshold of 15 percent of the donors' blood volume not to be exceeded during hemapheresis procedures. No data demonstrating the suitability of this approach exist. The blood volumes of 1204 plasmapheresis donors were calculated with different formulae that utilized either body weight or body surface area. Extracorporeal blood volumes of these donors were determined for a commonly used intermittent-flow plasmapheresis machine known to result in a large extracorporeal blood volume. A validated model was employed that calculated the fluid volume shifts occurring during the procedure. The records of all plasmapheresis procedures of these donors were retrospectively reviewed for circulatory reactions. The median extracorporeal volumes ranged from 14 to 17 percent of the blood volume at a donor Hct level of 0.40 to 0.48 L per L for men and from 17 to 20 percent at a Hct level of 0.36 to 0.44 L per L for women. In more than 60 percent of male and more than 90 percent of female donors, extracorporeal volumes exceeded 15 percent of the blood volume during plasmapheresis. In this subgroup, 65 percent of male and 75 percent of female donors never presented with any signs of circulatory reactions. Application of an arbitrary threshold of 15 percent of the donors' blood volume not to be exceeded during hemapheresis procedures is expected to lead to an unjustified deferral rate in plasmapheresis donors.

Collection of peripheral progenitor cells in paediatric patients with a new programme for the collection of mononuclear cells.

When harvesting peripheral progenitor cells (PPC) in children, the special situation of their circulatory system has to be taken into account. Therefore, extracorporeal blood volume and product volume should be small to avoid side effects. Nine children (age 2-14 years, weight 12.8-58.5 kg) with malignancies underwent 10 PPC collections with the MNC programme of the Amicus blood cell separator. The disposable kit was primed with red blood cells (RBCs) or human albumin to avoid circulatory side effects. The children were monitored for blood pressure and heart rate during the whole apheresis procedure. A median blood volume of 4,577 ml (range 3,536-8,596 ml) was processed in a separation time of 270 min (range 176-331 min). The median product weight was 81 g (range 53-107 g) and the yield of CD 34 antigen expressing cells was 12.5 x 10(6)/kg body weight (range 1.8-26 x 10(6)/kg body weight). Only one child had to undergo a second apheresis to collect the desired transplantation dose. The median platelet contamination of the product was 0.32 x 10(11) (0.13-0.85 x 10(11)). No circulatory side effects were observed. Blood flow alarms occurred in seven of ten aphereses and one collection had to be terminated due to insufficient flow. PPC can be efficiently collected in children with the MNC programme without circulatory side effects. The platelet contamination of the product was low due to the elutriation principle of the collection process, thereby avoiding thrombocytopenic bleeding episodes in the patients.

Modification of the leukapheresis procedure for use in rhesus monkeys (Macaca mulata).

One of the most serious problems in applying leukapheresis to human infants is the large extracorporeal blood volume (ECV), resulting in substantial loss of platelets and red blood cells (RBCs). In this study, we developed a safe and effective modified procedure to collect peripheral blood stem cells (PBSCs) from rhesus monkeys (Macaca mulata) using a Baxter CS3000+ Blood Cell Separator (Baxter, Deerfield, IL) with several devices that reduced chamber size and shortened the standard apheresis kit to decrease ECV from 130 to 70 ml. Pump speed was controlled by monitoring hematocrit values and platelet counts during leukapheresis. This system makes it possible to perform safe and effective leukapheresis in rhesus monkeys whose body weight is similar to that of human infants. A total of 12 leukapheresis procedures were performed in nine monkeys and resulted in the collection of sufficient numbers of white blood cells (mean, 1.38 x 10(9) cells/kg), CD34(+) cells (mean, 17.80 x 10(6) cells/kg), mononuclear cells (mean, 3.67 x 10(8) cells/kg), and colony forming units (mean, 75.02 x 10(6) cells/kg) in all cases. In addition, no complications, such as anemia or thrombocytopenia, occurred after leukapheresis. This modified leukapheresis procedure will be useful to test new approaches in gene therapy, perform organ transplantation using nonhuman primates, and collect PBSCs from human infants in a noninvasive manner. Our nonhuman primate model provides an important framework for such future clinical studies.

Plasmapheresis and renal replacement therapy in children.

The use of extracorporeal techniques for the treatment of pediatric diseases has expanded dramatically in the past decade. During this time, experience with both plasmapheresis and renal replacement therapy has become commonplace in ICUs and nephrology programs throughout the world. The indications for these therapies range through treatment of vasculitis, drug removal, support from inborn error metabolism, multiorgan system failure, primary renal disease, and sepsis. Because these therapies are somewhat intermingled based on the commonality of the need for vascular access, extracorporeal blood volumes, and bedside nursing support, and furthermore because the indications for these may overlap, these therapies are often used in tandem or parallel to support the child with illness.