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Various modalities of high-intensity hemodialysis are gathering increasing popularity. Some of the advantages of these new dialysis regimens are presented. Time and the increasing use of these novel approaches will ultimately determine their role in the overall management of patients with end-stage renal disease.
Despite the fact that no new clinical outcome studies comparing intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) for acute kidney injury (AKI) have been published in the past year, two meta-analyses addressing the topic (Bagshaw et al, Crit Care Med 2008; 36: 610–7, and Pannu et al, JAMA 2008; 299: 793–805) have been published recently. With respect to randomized controlled trials (RCTs), there was a substantial overlap between the studies considered in the analysis by Bagshaw et al and those considered in the analysis by Pannu et al. Although neither metaanalysis showed a benefit for either modality with respect to mortality or renal recovery, the two publications offered vastly different conclusions. Bagshaw et al concluded it is impossible to make any definitive recommendations about dialysis modality choice in AKI because previous studies were not adequately powered and failed to standardize for treatment dose. On the other hand, because the metaanalysis of Pannu et al demonstrated equivalent patient outcomes, and in light of the lower costs of IHD, they suggested that alternate-day hemodialysis should become the preferred therapy in many critically ill patients. As the clinical practice recommendations made by Pannu and colleagues have very important implications, we believe their analysis should be critically assessed. In this review, the weaknesses of the RCTs considered in the meta-analysis by Pannu et al are presented. Furthermore, the assumption by Pannu et al that IHD is associated with lower costs than CRRT is challenged, as they did not consider adequately both the short-term and long-term costs associated with the dialytic management of AKI patients. Based on our critical analysis, we believe the AKI dialytic treatment approach recommended by the JAMA investigators (Pannu et al) is not supported by the aggregate of the available clinical outcome data and, therefore, remains highly controversial.
We would like to join with others in the AKI field by strongly recommending that investigators and other clinicians stop trying to make conclusive determinations about dialysis modalities when robust supportive data simply are not available. Instead of additional intermodality comparisons, the focus of future clinical research should be toward generating high-quality data on intramodality interventions, such as treatment dose and timing of treatment initiation. In this regard, at least for CRRT, we anxiously await the results of the ongoing RCTs evaluating the effect of CRRT dose on patient outcome.
To determine if circuit life is influenced by a higher pre-dilution volume used in CVVH when compared with a lower pre-dilution volume approach in CVVHDF.
A comparative crossover study. Cases were randomized to receive either CVVH or CVVHDF followed by the alternative treatment.
All patients ≥ 18 yrs of age who required CRRT while in ICU were eligible to participate, but excluded if coagulopathic, thrombocytopenic or unable to receive heparin. Based on an intention-to-treat, 45 patients were randomized to receive either CVVH or CVVHDF followed by the alternative treatment. Setting: A 24-bed, tertiary, medical and surgical adult intensive care unit (ICU).
Blood flow rate, vascular access device and insertion site, hemofilter, anticoagulation and machine hardware were standardized. An ultrafiltrate dose of 35 ml/ kg/h delivered pre-filter was used for CVVH. A fixed pre-dilution volume of 600 mls/h with a dialysate dose of 1 L was used for CVVHDF.
Thirty-one patients received CVVH or CVVHDF out of 45 participants followed by the alternative technique. There was a significant increase in circuit life in favor of CVVHDF (median=16 h 5 min, range=40 h 23 min) compared with CVVH (median=6 h 35 min, range=30 h 45 min). A Mann-Whitney U test was performed to compare circuit life between the two different CRRT modes (Z=-3.478, p<0.001). Measurements of circuit life on the 93 circuits which survived to clotting (50 CVVH and 43 CVVHDF) were log transformed prior to under taking a standard multiple regression analysis. None of the independent variables - activated prothrombin time (aPTT), platelet count, heparin dose, patient hematocrit or urea - had a coefficient partial correlation >0.09 (coefficient of the determination=0.117) or a linear relationship which could be associated with circuit life (p=0.228).
Pre-diluted CVVHDF appeared to have a longer circuit life when compared to high volume pre-diluted CVVH. The choice of CRRT mode may be an important independent determinant of circuit life.
To compare the acid-base balance effects of two different citrate doses for regional citrate anticoagulant (RCA) for continuous veno-venous hemofiltration (CVVH).
We used a commercial citrate fluid (citrate concentration: 11mmol/L) from July 2003 to July 2004 (period A) in 22 patients; then changed to a new citrate fluid (citrate concentration: 14mmol/L) from July 2004 to Feb 2005 (Period B) in 21 patients. Replacement fluid rate was fixed at 2,000 ml/h. We measured all relevant variables for acid-base analysis according to the Stewart-Figge methodology.
After commencement of RCA-CVVH, there was a change in bicarbonate and base excess (BE) toward acidosis for both fluids. This change was significantly different between period A and B at 6 and 12 hours (pH: p<0.01, BE: p<0.05) with greater decreases with the 11 mmol/L citrate fluid. These changes were mostly secondary to an increase in the strong ion difference (SID) and occurred despite an increased strong ion gap (SIG) (+0.5 mEq/L vs. +1.5 mEq/L; p<0.01) in the higher citrate concentration fluid. Cessation of RCA-CVVH was associated with short-lived differences in bicarbonate and SIG which were similar to those seen on initiation of RCA-CVVH but in the opposite direction.
A small increase This was partly offset by an increase in SIG, consistent with increased citratemia. Cessation of treatment showed a differential improvement in SIG also consistent with disposal of therapy-associated citrate. These observations might assist clinicians in interpreting acid-base changes during RCA-CVVH.in citrate infusion rate caused an alkalinizing increase in SID.
This study examines the effect of a change from the standard 4–5 hours 3 times a week of online hemodiafiltration (OL-HDF) to 2–2.5 hours daily (6 times a week) OL-HDF, on acid-base balance, and attempts assess the modifications of acid-base parameters, ionic concentration, and electrical charges of albumin and phosphate available for diffusion and convection mechanisms across the membrane and subsequent infusion.
In 18 patients on online HDF, blood gas, electrolytes (Na, K, Cl), lactate, phosphate, albumin, apparent strong ion difference (SIDa), effective strong ion difference (SIDe), strong ion gap (SIG), anion gap (AG), and bicarbonate and pH time-averaged concentration (TAC) and time-averaged deviation (TAD) variables were evaluated at baseline, and 1, 3, 6, 9, and 12 months after patients were switched to daily OL-HDF. Additionally, in 12 patients, the same parameters measured simultaneously at dialyzer inlet, outlet, and after reinfusion were studied.
Throughout the study, weekly single-pool Kt/V, equilibrated Kt/V, and TAC urea remained constant. However, standard Kt/V increased and TAD urea decreased on daily OL-HDF. There were no statistical differences during the time span of 12 months in pH, cations (Na, K), anions (Cl, HCO–3 AG, and lactate), or SIDa, SIDe, and SIG pre-HDF; while pH and HCO3– TAD decreased from 0.02 and 1.02 ± 0.74 mEq/L, to 0.01 and 0.64 ± 0.52 mEq/L, respectively (p<0.01). Net albumin charge and AG increased significantly at dialyzer outlet and decreased after reinfusion.
We did not observe changes in the acid-base balance in patients who switched from 3 times a week to short daily OL-HDF. The main benefit observed was a lower pH and bicarbonate TAD. This shows a better physiology for daily OL-HDF.
Muscular counterpulsation (MCP) was developed for circulatory assistance by stimulation of peripheral skeletal muscles. We report on a clinical MCP study in patients with and without chronic heart failure (CHF).
MCP treatment was applied (30 patients treated, 25 controls, all under optimal therapy) for 30 minutes during eight days by an ECG-triggered, battery-powered, portable pulse generator with skin electrodes inducing light contractions of calf and thigh muscles, sequentially stimulated at early diastole. Hemodynamic parameters (ECG, blood pressure and echocardiography) were measured one day before and one day after the treatment period in two groups: Group 1 (9 MCP, 11 no MCP) with ejection fraction (EF) above 40% and Group 2 (21 MCP, 14 no MCP) below 40%. In Group 2 (all patients suffering from CHF) mean EF increased by 21% (p<0.001) and stroke volume by 13% (pp<0.001), while end systolic volume decreased by 23% (pp<0.001). In Group 1, the increase in EF (6%) and stroke volume (8%) was also significant (pp<0.05) but less pronounced than in Group 2. Physical exercise duration and walking distance increased in Group 2 by 56% and 72%, respectively.
Noninvasive MCP treatment for eight days substantially improves cardiac function and physical performance in patients with CHF.
The transplantation of primary human hepatocytes is a promising approach in the treatment of specific liver diseases. However, little is known about the fate of the cells following application. Magnetic resonance imaging (MRI) could enable real-time tracking and long-term detection of transplanted hepatocytes. The use of superparamagnetic iron oxide particles as cellular contrast agents should allow for the non-invasive detection of labelled cells on high-resolution magnetic resonance images. Experiments were performed on primary human hepatocytes to transfer the method of detecting labelled cells via clinical MRI into human hepatocyte transplantation. For labelling, Tat-peptide modified nano-sized superparamagnetic MagForce particles were used. Cells were investigated via a clinical MR scanner at 3.0 Tesla and the particle uptake within single hepatocytes was estimated using microscopic examinations. The labelled primary human hepatocytes were clearly detectable by MRI, proving the feasibility of this new concept. Therefore, this method is a useful tool to investigate the effects of human hepatocyte transplantation and to improve safety aspects of this method.
Embryonic stem cells (ESCs) are of significant interest as a renewable source of nonproliferating cells. Differentiation of ESCs is initiated by the formation of embryoid bodies (EBs). Standard methods of EB formation are limited in their production capacity, in any variations in EB size and formation of EBs through frequent passages. Here we have reported the utility of a microencapsulation technique for overcoming these limitations by mass production of mouse ESCs in alginate beads called ESC spheres.
The mouse ESCs were encapsulated in 1.2% alginate solution and cocultured on a feeder layer. The cells were evaluated by flow cytometry, in vitro differentiation, immunofluorescence, and reverse transcriptase polymerase chain reaction (RT-PCR).
Analysis of encapsulated ESC spheres by flow cytometry showed similar percentages of Oct-4 and stage-specific embryonic antigen-1 (SSEA-1) expression in comparison with routine culture of ESCs. Moreover, the ESC spheres maintained a pluripotency potential which was comparable with ESCs cultured on feeder cells directly, as demonstrated by immunofluorescence and RT-PCR.
The results demonstrated that alginate encapsulation as a simple bioreactor, provides a scalable system for mass undifferentiated ESC sphere production with similar sizes and without the need for frequent passages for differentiation and clinical and pharmaceutical applications.
To describe the effects on cerebral blood flow velocity (CBFV) of intermittent opening of the venoarterial bridge (VA bridge) during venoarterial extracorporeal membrane oxygenation (VA-ECMO).
Prospective study in 22 newborns during VA-ECMO. CBFV was measured in the perical-losal artery by Doppler ultrasound. Changes in peak systolic flow velocity (PSV), end diastolic flow velocity (EDV) and time-averaged mean flow velocity (TAM) on day 1, 2, 3, and 5 and at low ECMO flow (50–150 ml/min) were analyzed (mean percentage±standard deviation (t-tests, p<0.05)). Changes >25% were considered relevant. The relationship between changes in CBFV and ECMO flow rate (Pearson correlation, p<0.01) was studied.
Opening of the VA bridge resulted in statistically significant and relevant decreases in PSV (35 ± 18%), EDV (93 ± 15%) and TAM (68 ± 13%), persisting during the consecutive days of treatment. Smaller changes in CBFV at low ECMO flow were statistically significant and mostly relevant: PSV (15 ± 7%), EDV (76 ± 21%) and TAM (40 ± 12%). Changes in CBFV were positively correlated to the ECMO flow. Conclusion: Use of the VA bridge results in significant and relevant ECMO flow-dependent changes in CBFV, persisting during the treatment. The VA bridge should be used in such a way as to allow regular unclamping to be omitted.
A new process, based on the micro-co-extrusion of preceramic precursors, has been studied for manufacturing ceramic microelectrodes to be used in biomedical applications. Commercially available silicon polymers were applied and proper doping resulted in electrically conductive ceramic filaments. Chemical reticulation and high-temperature pyrolysis were applied to convert the polymeric resins into Si-O-C ceramic materials. Circular microelectrodes were manufactured with diameters between 100 μm and 5 mm with a different number of inner conductive lines (from 1 to 80). The flexural strength of the filaments depended on the outer diameter size; doping with carbon black produced filaments with an average conductivity of approximately 0.4 S/cm for a 50% weight carbon black load. The results achieved by in vitro studies confirmed a good biological performance of Si-O-C ceramic structures with both hard and soft tissue cell models.
Our 18-year old female patient suffered from microscopic polyangiitis. After invasive diagnostics, a diffuse alveolar hemorrhage occurred, leading to acute lung failure. In spite of differential ventilation, respiratory insufficiency and lactate-acidosis increased quickly. Due to the massive hemorrhage, a pumpless extracorporeal lung assist was implanted and, after six hours, low-dose heparinization was started. In response to this therapy, hypercapnia and acidosis improved quickly and were completely eliminated within 24 hours. Simultaneously, treatment with prednisolon and cyclophosphamid was started. After 7 days, the patient's conditions allowed weaning from the pumpless extracorporeal lung assist and after 9 days she was extubated.
In conclusion, the pumpless lung assist was shown to be a very practical option to treat the most serious forms of hypercapnia, especially for patients disposed to diffuse bleeding.
