NDUFAF3 variants that disrupt mitochondrial complex I assembly may associate with cavitating leukoencephalopathy.

Genetic abnormalities in mitochondrial complex assembling factors are associated with leukoencephalopathy. We present a 1-year-old girl with consciousness disturbance after a respiratory infection. Brain MRI revealed leukoencephalopathy with bilaterally symmetrical hyperintensity in the substantia nigra, medial thalamic nuclei, and basal nuclei, as well as cavities in the cerebral white matter and corpus callosum. Lactate levels in the spinal fluid were high, while magnetic resonance spectroscopy of the cerebral white matter and basal nuclei showed high peak lactate levels, suggesting mitochondrial dysfunction. The respiratory enzyme activity of complex I was reduced to 17% to 21% in skeletal muscle. Whole exome sequencing identified compound heterozygous variations in NDUFAF3, involved in the assembly of mitochondrial complex I (c.342_343insGTG:p.117Valdup, c.505C > A:p.Pro169Thr). Two-dimensional, blue-native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate-PAGE revealed reductions in Q-module (NDUFS2, NDUFS3, and NDUFA9) and P-module (NDUFB10 and NDUFB11) subunits, indicating disruption of mitochondrial complex I assembly. Our report expands the spectrum of clinical phenotypes associated with pathogenic variants of NDUFAF3.

Factors predicting successful discontinuation of continuous renal replacement therapy.

This multicentre, retrospective observational study was conducted from January 2010 to December 2010 to determine the optimal time for discontinuing continuous renal replacement therapy (CRRT) by evaluating factors predictive of successful discontinuation in patients with acute kidney injury. Analysis was performed for patients after CRRT was discontinued because of renal function recovery. Patients were divided into two groups according to the success or failure of CRRT discontinuation. In multivariate logistic regression analysis, urine output at discontinuation, creatinine level and CRRT duration were found to be significant variables (area under the receiver operating characteristic curve for urine output, 0.814). In conclusion, we found that higher urine output, lower creatinine and shorter CRRT duration were significant factors to predict successful discontinuation of CRRT.

Effect of perfusion pressure on the splanchnic circulation after CPB: a pilot study.

BACKGROUND: The impact of different blood pressure targets is unknown for post cardiac surgery patient in the intensive care unit. We, therefore, investigated the effects of a mean arterial pressure (MAP) target of 65 or 85 mmHg on splanchnic oxygenation, metabolic function, cytokine regulation and gastric tonometry after cardiopulmonary bypass. METHODS: Sixteen patients were randomized to the HLH group (high-low-high) where MAP of 85-65-85 mmHg was targeted or the LHL group where MAP 65-85-65 mmHg was targeted with norepinephrine infusion. RESULTS: MAP targets were achieved in all patients at all timepoints (64 ± 3, 84 ± 4; 65 ± 5, LHL group; vs. 84 ± 3; 66 ± 2; 85 ± 5 mmHg, HLH group). At corresponding timepoints, hepatic venous saturation was 41 ± 15%; 58 ± 24%; 56 ± 21% in the LHL group vs. 50 ± 19%; 43 ± 20%; 41 ± 18% in the HLH group (P<0.05). No changes were observed in cardiac output, global or trans-splanchnic lactate levels and cytokine levels or in gastric tonometry CO2. CONCLUSION: Achieving a MAP target of 85 mmHg by means of norepinephrine infusion after CPB appears safe for the splanchnic circulation.

Radiation exposure to anaesthetists during endovascular procedures.

Medical radiation exposure increases the likelihood of cataract formation. A personal dosimeter was attached to the left temple of 77 anaesthetists during 45 endovascular aortic aneurysm repairs and 32 interventional neuroradiology procedures. Compared with interventional neuroradiology, the median (IQR [range]) total radiation dose emitted by fluoroscopic equipment was significantly lower during endovascular aortic aneurysm repair (4175 (3127-5091 [644-9761]) mGy than interventional neuroradiology (1420 (613-2424 [165-10,840]) mGy, p < 0.001). However, radiation exposure to the anaesthetist's temple was significantly greater during endovascular aortic aneurysm repair (15 (6-41 [1-109]) µSv) than interventional neuroradiology (4 (2-8 [0-67]) µSv, p < 0.001). These data suggest that anaesthetists at our institution would have to deliver anaesthesia for ~1300 endovascular aortic aneurysm repairs and ~5000 interventional neuroradiology cases annually to exceed the general occupational limits, and ~10,000 endovascular aortic aneurysm repairs and ~37,500 interventional neuroradiology cases to exceed the ocular exposure limits recommended by the International Commission on Radiological Protection. Nevertheless, anaesthetists should be aware of the risk of ocular radiation exposure, and reduce this by limiting the time of exposure, increasing the distance from the source of radiation, and shielding.

A case of cystadenocarcinoma of the ectopic salivary gland: comparison of pre-operative ultrasound, CT and MR images with the pathological specimen.

Cystadenocarcinoma is a rare salivary gland tumour. Only a few case studies have provided pre-operative images of these tumours. This report demonstrates the case of a 28-year-old male with cystadenocarcinoma arising from an ectopic salivary gland with lymph node metastasis in the right upper neck. Ultrasound including Doppler images showed two masses with scant vascular flow. One was a hyperechoic mass enclosed within a low echoic cystic lesion and the other was a solid hypoechoic mass. Contrast enhancement CT scans demonstrated a ring enhanced mass and weakly homogeneous enhanced masses in the right upper neck. Dynamic studies showed increased enhancement in delayed phase CT that was the same as that in other malignant salivary gland tumours. Moderate to slightly high signal intensity was seen on T(1) weighted MR images and axial T(2) weighted MR images showed one heterogeneous mass in a high signal lesion and a moderate to high signal intensity mass. The authors discuss the pre-operative findings of ultrasound with Doppler imaging of this neoplasm, and CT findings including dynamic study images and MRI, comparing the findings with the post-operative pathological features of the tumour.

Differential effects of urinary and recombinant chorionic gonadotropin on oxidative stress responses in decidualizing human endometrial stromal cells.

Human chorionic gonadotropin (hCG) is one of the earliest signals secreted by the implanting embryo. In addition to its well-known luteotropic function in early pregnancy, hCG also acts directly on decidualizing endometrium. Recently, we demonstrated that recombinant hCG (rhCG) prevented apoptosis in decidualizing human endometrial stromal cells (HESCs) exposed to oxidative stress. Two hCG preparations are widely used clinically: rhCG, produced by recombinant DNA technology, and urinay hCG (uhCG), extracted from urine of post-menopausal women. However, an analysis of the direct effects of rhCG and uhCG on the decidual phenotype of HESCs has not yet been done. In this study, we investigated the effects of uhCG and rhCG on the morphological and functional profiles of decidualizing HESCs. We demonstrate that neither rhCG nor uhCG alter the morphological appearance of the decidual HESC cultures, although rhCG but not uhCG attenuated prolactin expression, a major decidual marker protein. Moreover, rhCG, but not uhCG, protected decidualizing HESCs from oxidative cell death, mediated at least in part by two major mechanisms. First, rhCG, but not uhCG, enhances the expression of manganese superoxide dismutase, a cardinal enzyme in the cellular defense against oxidative damage. Second, rhCG signaling selectively limits activation of the apoptotic machinery in decidualizing HESCs by enhancing Bcl-2 expression whereas uhCG induces the expression of Fas ligand. Our results suggest that rhCG might be a preferable agent to protect the maternal decidua against oxidative damage in pregnancy, especially at the time of implantation and beyond.

Inhibition of N-methyl-D-aspartate receptor activity resulted in aberrant neuronal migration caused by delayed morphological development in the mouse neocortex.

Embryonic and neonatal neocortical neurons already express functional N-methyl-D-aspartate (NMDA) receptors before they form synapses. To elucidate the role of NMDA receptors in neuronal migration in the developing neocortex, we visualized radially migrating neurons by transferring the enhanced green fluorescent protein (EGFP) gene into the ventricular zone (VZ) of the mouse neocortex using in utero electroporation at E15.5. Two days later, we prepared neocortical slices and examined the EGFP-positive cells using time-lapse imaging in the presence of the NMDA receptor antagonist Cerestat. The EGFP-positive cells generated in the VZ in the control slices exhibited a multipolar morphology, but within several hours they became bipolar (with a leading process and an axon-like process) and migrated toward the pial surface. By contrast, many of the multipolar cells in the Cerestat-treated slices failed to extend either process and become bipolar, and frequently changed direction, although they ultimately reached their destination even after Cerestat-treatment. To identify the molecules responding for mediating NMDA signaling during neuronal migration and the changes in morphology observed above, we here focused on Src family kinases (SFKs), which mediate a variety of neuronal functions including migration and neurite extension. We discovered that the activity of Src and Fyn was reduced by Cerestat. These findings suggest that NMDA receptors are involved in neuronal migration and morphological changes into a bipolar shape, and in the activation of Src and Fyn in the developing neocortex.

Pigment epithelium-derived factor up-regulation induced by memantine, an N-methyl-D-aspartate receptor antagonist, is involved in increased proliferation of hippocampal progenitor cells.

Memantine is classified as an NMDA receptor antagonist. We recently reported that memantine promoted the proliferation of neural progenitor cells and the production of mature granule neurons in the adult hippocampus. However, the molecular mechanism responsible for the memantine-induced promotion of cellular proliferation remains unknown. In this study we searched for a factor that mediates memantine-induced cellular proliferation, and found that pigment epithelium-derived factor (PEDF), a broad-acting neurotrophic factor, is up-regulated in the dentate gyrus of adult mice after the injection of memantine. PEDF mRNA expression increased significantly by 3.5-fold at 1 day after the injection of memantine. In addition, the expression level of PEDF protein also increased by 1.8-fold at 2 days after the injection of memantine. Immunohistochemical study using anti-PEDF antibody showed that the majority of the PEDF-expressing cells were protoplasmic and perivascular astrocytes. Using a neurosphere assay, we confirmed that PEDF enhanced cellular proliferation under the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor (EGF) but was not involved in the multilineage potency of hippocampal progenitor cells. Over expression of PEDF by adeno-associated virus, however, did not stimulate cellular proliferation, suggesting PEDF per se does not promote cellular proliferation in vivo. These findings suggest that the memantine induced PEDF up-regulation is involved in increased proliferation of hippocampal progenitor cells.

Elastic plasma protein film blended with platelet releasate accelerates healing of diabetic mouse skin wounds.

BACKGROUND AND OBJECTIVES: The growth factors derived from platelets and plasma proteins mediate the wound-healing process that is characterized by the sequential migration and differentiation of several cell populations that give rise to angiogenesis, collagen synthesis, wound contraction, and re-epithelialization. To evaluate the efficacy of the blood-derived factors in wound healing, we examined a novel wound dressing consisting of concentrated human plasma proteins and platelet releasate (CPPP). MATERIALS AND METHODS: To generate CPPP, plasma proteins and platelets in the peripheral blood (n = 5) were concentrated with the cold ethanol precipitation method. The thrombin obtained from the same blood unit and calcium chloride (CaCl(2)) were mixed to a concentrate. The CPPP has enough strength to dress cutaneous wounds and contains large amounts of cytokines and fibronectin. We applied the CPPP to excisional skin wounds in genetically healing-impaired model mice (n= 5) and the wounds were evaluated 10 days after the operation. RESULTS: The area of CPPP-treated wounds decreased significantly compared with that of the control wounds (65% vs. 94% of the original size, respectively, P= 0.032). The immunostained section revealed a striking effect of CPPP on vascularization compared with the control wounds (13.2 vs. 2.7 vessels per mm(2) as mean vascular density observed in the sections, respectively, P= 0.013). CONCLUSIONS: Our results suggest that CPPP is a promising biologically active dressing for full-thickness skin wounds. CPPP can be an entirely autologous biological dressing, suggesting that it is free from the risk of transmission of pathogens through blood products.

Patient and kidney survival by dialysis modality in critically ill patients with acute kidney injury.

Using a large, international cohort, we sought to determine the effect of initial technique of renal replacement therapy (RRT) on the outcome of acute renal failure (ARF) in the intensive care unit (ICU). We enrolled 1218 patients treated with continuous RRT (CRRT) or intermittent RRT (IRRT) for ARF in 54 ICUs in 23 countries. We obtained demographic, biochemical and clinical data and followed patients to either death or hospital discharge. Information was analyzed to assess the independent impact of treatment choice on survival and renal recovery. Patients treated first with CRRT (N=1006, 82.6%) required vasopressor drugs and mechanical ventilation more frequently compared to those receiving IRRT (N=212, 17.4%), (p<0.0001). Unadjusted hospital survival was lower (35.8% vs. 51.9%, p<0.0001). However, unadjusted dialysis-independence at hospital discharge was higher after CRRT (85.5% vs. 66.2%, p<0.0001). Multivariable logistic regression showed that choice of CRRT was not an independent predictor of hospital survival or dialysis-free hospital survival. However, the choice of CRRT was a predictor of dialysis independence at hospital discharge among survivors (OR: 3.333, 95% CI: 1.845 - 6.024, p<0.0001). Further adjustment using a propensity score did not significantly change these results. We conclude that worldwide, the choice of CRRT as initial therapy is not a predictor of hospital survival or dialysis-free hospital survival but is an independent predictor of renal recovery among survivors.

A pilot study of high-adsorption hemofiltration in human septic shock.

BACKGROUND: To compare the hemodynamic and biological effects of high-adsorption continuous veno-venous hemofiltration (CVVH) with standard CVVH in septic shock. METHODS: In a randomized cross-over clinical trial twelve patients with septic shock and multiple organ failure were enrolled at a tertiary intensive care unit. Patients were allocated to either 9 hours of high-adsorption hemofiltration (CVVH with 3 hourly filter change using AN69 hemofilters - 3FCVVH) or 9 hours of standard hemofiltration (CVVH without filter change - 1F-CVVH). RESULTS: Changes in hemodynamic variables, dose of noradrenaline required to maintain a mean arterial pressure greater than 75 mmHg and plasma concentrations of cytokines (IL-6, IL-8, IL-10 and IL-18) were measured. A 9-hour period of 3F-CVVH was associated with greater reduction in noradrenaline dose than a similar period of 1F-CVVH (median reduction: 16 vs. 3.5 microg/min, p=0.036; median percentage reduction: 48.1% vs. 17.5%, p=0.028). Unlike 1F-CVVH, 3F-CVVH was associated with a reduction in the plasma concentration of IL-6, IL-10 and IL-18 at 9 hours and a significant decrease 30 minutes after additional filter changes (IL-6: p<0.01, p<0.01; IL-10: p=0.03, p=0.016 and IL-18: p=0.016, p<0.01, respectively). Both, 3F-CVVH and 1F-CVVH were associated with decreased plasma concentrations of IL-8 at 9 hours (p<0.01, p<0.01, respectively). In a confirmatory ex-vivo experiment IL-6 concentrations substantially decreased during 3F-CVVH (at baseline 511 pg/mL and at end: 21 pg/mL) whereas IL-6 concentrations increased in control blood (at baseline 511 pg/mL and at end: 932 pg/mL). CONCLUSIONS: High-adsorption CVVH appears more effective than standard CVVH in decreasing noradrenaline requirements and plasma concentrations of cytokines in septic shock patients.

Prognosis of small thyroid cancer in patients with Graves' disease.

BACKGROUND: To find the best ways to follow up patients with small thyroid cancer (STC; 1 cm or less in diameter) and concomitant Graves' disease, this study examined whether such patients had the same excellent prognosis as those with STC without Graves' disease. METHODS: Between 1970 and 1996, 2199 patients were diagnosed as having STC by pathology after thyroidectomy. Of those, 509 patients (33 males and 476 females, mean age 43.5 years) underwent thyroidectomy for Graves' disease. Control patients with STC without Graves' disease were matched for age, sex, treatment year and tumour size (33 males and 476 females, mean age 44.0 years). RESULTS: Patients with STC and Graves' disease had a longer disease-free survival than those with STC alone (99 and 93 per cent at 20 years' follow-up, respectively; P < 0.001). The Cox's proportional hazard analysis showed that concomitant Graves' disease and age at surgery are more significant factors for predicting disease-free survival than surgical procedures. CONCLUSION: Patients who undergo thyroidectomy for Graves' disease and are found to have STC have an excellent prognosis and longer disease-free survival than patients with STC alone.

Visualization of microglia in living tissues using Iba1-EGFP transgenic mice.

Microglia are thought to play important roles not only in repairing injured tissue but in regulating neuronal activity, and visualizing the cells is very useful as a means of further investigating the function of microglia in vivo. We previously cloned the ionized calcium-binding adaptor molecule 1 (Iba1) gene, which is expressed selectively in microglia/microphages. To generate new transgenic mice to visualize microglia with enhanced green fluorescent protein (EGFP), we here constructed a plasmid carrying EGFP cDNA under control of the Iba1 promoter. This construct was injected into C57B/6 mouse zygotes, and the Iba1-EGFP transgenic line was developed. Fluorescent in-situ hybridization analysis revealed that the Iba1-EGFP transgene was located on chromosome 11D. No obvious defects were observed during development or in adulthood, and the EGFP fluorescence remained invariant over the course of at least four generations. Judging from the immunoreactivity with anti-Iba1 antibody, all EGFP-positive cells in the adult brain were ramified microglia. In the developing transgenic embryos, EGFP signals were detected as early as embryonic Day 10.5. The most prominent EGFP signals were found in forebrain, spinal cord, eye, foreleg, yolk sac, liver, and vessel walls. At postnatal Day 6, clear EGFP signals were observed in the supraventricular corpus callosum, known as "fountain of microglia", where ameboid microglia migrate into the brain parenchyma and mature into ramified microglia. Iba1-EGFP transgenic mice thus permit observation of living microglia under a fluorescence microscope and provide a useful tool for studying the function of microglia in vivo.

A pilot study of pulse contour cardiac output monitoring in patients with septic shock.

OBJECTIVE: To assess the relationship between PiCCO-derived signals and conventional measures of pre-load and gas exchange in patients with septic shock. METHODS: Prospective observational study of 23 patients with septic shock. Scheduled collection of clinical, conventional haemodynamic and PiCCO derived variables. Statistical analysis of correlations. RESULTS: Patients had a mean SAPS II score of 53.5 +/- 14.5 with 78.3% on mechanical ventilation at PiCCO insertion. PiCCO monitoring lasted a mean of 4.3 +/- 2.9 days. SAPS II predicted 28-day mortality was 54.2%, while actual mortality was 39.1%. At PiCCO insertion, there was an inverse correlation between cardiac (CI) and extravascular lung water index (EVLWI) (r = -0.442; p < 0.05). During treatment, the most significant correlation was between the PiCCO-derived global end-diastolic volume index (GEDVI) and PaO(2)/F(I)O(2) ratio (r = 0.386; p < 0.01). There was also a correlation between changes in GEDVI and changes in CI (r = 0.329; p < 0.01). Increases in EVLWI correlated with decreases in PaO(2)/F(I)O(2) ratio( )(r = -0.332; p < 0.01). CONCLUSIONS: PiCCO-derived pre-load and extravascular lung water signals show logical associations with conventional indirect indicators of haemodynamic and fluid status suggesting physiological and clinical relevance.

A before and after trial of the effect of a high-dependency unit on post-operative morbidity and mortality.

OBJECTIVE: It has been suggested that the availability of a high-dependency unit (HDU), to facilitate graded admission to, and discharge from, an intensive care unit (ICU), might decrease post-operative morbidity. We wished to determine whether the addition of a 4-bed HDU to a tertiary 17-bed ICU facility at a University-affiliated hospital would decrease post-operative morbidity and mortality. PATIENTS AND METHODS: A prospective controlled before-and-after trial was performed with the opening of a 4-bed HDU. Consecutive patients admitted to hospital for major surgery during a 4-month control (pre-HDU) phase and during a 4-month intervention (HDU) phase were studied for the incidence of serious adverse events (SAEs), mortality after major surgery and mean duration of hospital stay. RESULTS: There were 1319 operations performed in 1125 patients during the pre-HDU period and 1369 operations performed in 1127 patients during the HDU period. During the HDU period there was an excess in unscheduled surgery cases (674 during HDU vs. 531 during the pre-HDU period; p < 0.0001). In the pre-HDU period, there were 414 SAEs in 190 patients compared with 456 SAEs in 209 patients during the HDU period (NS). There were no significant changes in any of the individual SAEs measured except for the incidence of post-operative acute pulmonary edema, which increased from 19 cases to 46 during the HDU period (p = 0.028). This increase was associated with a greater number of patients requiring re-intubation (52 vs. 75 cases; p = 0.044). The introduction of an HDU had no effect on mortality (80 deaths vs. 76; NS) and failed to reduce mean hospital length of stay (21.8 vs. 24 days; NS). CONCLUSIONS: The introduction of a 4-bed HDU in a teaching hospital was associated with a marked increase in unscheduled surgery and failed to reduce the incidence of post-operative SAEs, post-operative mortality, and mean duration of hospital stay.

Super high flux hemodialysis at high dialysate flows: an ex vivo assessment.

BACKGROUND AND OBJECTIVES: The removal of cytokines by standard hemofiltration is limited. Super high flux membranes may significantly improve removal even when used in dialysis mode. We sought to measure cytokine clearance using a large surface super high-flux membrane and a standard hemodialysis setting. SETTING: ICU laboratory of a tertiary institution. SUBJECTS: Six healthy volunteers. METHODS: Blood form healthy volunteers was incubated for 4 hours with E. coli endotoxin to stimulate cytokine production. Cytokine containing blood was then circulated through a dialysis circuit at 3 different dialysate flow rates. Blood and dialysate were sampled for cytokine and albumin measurements and calculation of clearances. RESULTS: Super high-flux dialysis achieved high median cytokine clearances (IL-1 clearance of 106 ml/min, IL-6 clearance of 66.8 ml/min, IL-8 clearance of 61.7 ml/min and TNF clearance of 36.1 ml/min). Increasing dialysate flow rate from 300 to 500 ml/min did not significantly increase cytokine clearances. Albumin clearances however were between 2.7 and 5.4 ml/min. CONCLUSIONS: Cytokine dialysis is feasible at high dialysate flow rates yielding high cytokine clearances. Albumin loss, however, is appreciable and may require separate supplementation in the clinical setting.

Beta2-microglobulin clearance with super high flux hemodialysis: an ex vivo study.

BACKGROUND: Beta2m accumulation induces disease in patients with end-stage renal failure (ESRF). Thus, its removal from patients with ESRF appears desirable. Current dialysis technology, however, has limited effectiveness. AIMS: To measure beta2m clearance with a novel super high flux membrane. DESIGN: Ex vivo experimental study. SETTING: Intensive Care Laboratory of Tertiary institution. SUBJECTS: Six volunteers. MEASUREMENTS AND RESULTS: At a blood flow of 300 ml/min, the clearance of beta2-MG increased from 113.5 +/- 38.5 ml/min with a dialysate flow rate of 200 ml/min to 184.8 +/- 61.1 ml/min with a flow rate of 300 ml/min and 195.0 +/- 60.0 ml/min with a 500 ml/min flow rate. The clearance of albumin was 4.5 ml/min with a dialysate flow rate of 200 ml/min, 5.2 ml/min for a flow rate of 300 ml/min and 5.8 ml/min for a flow rate of 500 ml/min. CONCLUSIONS: High levels of beta2m clearance can be achieved with a super high flux membrane while albumin losses remain limited.

The acid-base effects of continuous hemofiltration with lactate or bicarbonate buffered replacement fluids.

OBJECTIVE: To evaluate, quantify and compare the effects of continuous veno-venous hemofiltration (CVVH) with lactate or bicarbonate-buffered replacement fluids on acid-base balance. DESIGN: Randomized double crossover study. SETTING: Intensive Care Unit of Tertiary Medical Center. PARTICIPANTS: Eight patients with severe acute renal failure. INTERVENTIONS: Random allocation to either 2 hours of isovolemic lactate-buffered (treatment A) CVVH or 2 hours of bicarbonate-buffered (treatment B) CVVH with cross over and with same procedure repeated the following day (double cross over). MEASUREMENTS AND RESULTS: Timed collections of arterial blood and ultrafiltrate (UF), measurement of blood and UF gases and lactate concentrations and calculation of buffer-base mass balance. At baseline, both groups of patients had a similar, slight metabolic alkalosis (pH: 7.45 vs. 7.45; BE 3.9 mEq/L for treatment A and 4.0 for treatment B) and a serum bicarbonate of 28.1 mmol/L for treatment A vs. 28.3 mmol/L for treatment B; all NS. This alkalosis was present despite slight hyperlactatemia in both groups (A: 2.4 mmol/L vs. B 2.8 mmol/; NS). Within 60 minutes of treatment, however, treatment A led to a significantly higher lactate concentration (3.9 vs 2.5 mmol/L; p = 0.0011), a significantly lower BE (2.3 vs 4.1 mEq/L; p = 0.0019) and a significantly lower bicarbonate concentration (26.7 vs. 28.3 mmol/L; p = 0.0038) in the presence of an unchanged PaCO2. These differences persisted during the study period. The UF of patients receiving treatment A contained more lactate (10.2 vs 2.9 mmol/L; p < 0.0001) and less bicarbonate (25.6 vs. 30.8 mmol/L; p < 0.0001) than treatment B resulting in a mean buffer-base balance of +20.4 mEq/h compared to -2.6 mEq/h for treatment B; p < 0.0001). CONCLUSIONS: CVVH with lactate-buffered replacement fluids induces iatrogenic hyperlactatemia. Such hyperlactatemia is associated with an acidifying effect despite a positive buffer-base balance.

Continuous renal replacement therapy: does technique influence electrolyte and bicarbonate control?

BACKGROUND AND OBJECTIVES: Different techniques of continuous renal replacement therapy (CRRT) might have different effects on electrolyte and acid-base control. The aim of this study was to determine whether continuous veno-venous hemodiafiltration (CVVHDF) or continuous veno-venous hemofiltration (CVVH) achieve better control of serum sodium, potassium and bicarbonate concentrations. DESIGN: Retrospective controlled study. SETTING: Two tertiary intensive care units. PATIENTS: Critically ill patients with acute renal failure (ARF) treated with CVVHDF (n=49) or CVVH (n=50). INTERVENTIONS: Retrieval of daily morning sodium and potassium values and arterial bicarbonate levels from computerized biochemical records before and after the initiation of CRRT for up to 2 weeks of treatment. Statistical comparison of findings. MEASUREMENTS AND RESULTS: Before treatment, abnormal (high or low) values were frequently observed for sodium (65.1% for CVVHDF vs. 80.0% for CVVH; NS), potassium (45.9% vs. 34.0%; NS), and bicarbonate (73.3% vs. 68.0%; NS). After treatment, however, CVVHDF was more likely to achieve serum sodium concentrations within the normal range (74.1% vs. 62.9%; p=0.0026). Both treatments decreased the mean serum potassium concentration over the first 48 h (p=0.0059 and p<0.0001, respectively), but there was no difference in terms of the normalization of serum potassium concentration during the entire treatment period (88.3% vs. 90.5%; NS). Both treatments increased the mean arterial bicarbonate concentration over the first 48 hours (p=0.011 and p<0.0001, respectively). However, CVVH was associated with a lower incidence of metabolic acidosis (13.8% for CVVH vs. 34.5% for CVVHDF; p<0.0001) and a higher incidence of metabolic alkalosis (38.9% vs. 1.1%; p<0.0001) during the entire treatment period. CONCLUSIONS: CRRT strategies based on different techniques have a significantly different impact on sodium and bicarbonate control.