Continuous Veno-venous Hemofiltration Therapy Research Articles

Analysis of Leukocyte Recruitment in Continuous Veno-Venous Hemofiltration with Regional Citrate vs. Systemic Heparin Anticoagulation.

Acute kidney injury (AKI) is a frequent complication in critically ill patients. Supportive treatment of AKI patients is based on renal-replacement therapy, including continuous veno-venous hemofiltration (CVVH). To limit clotting events on extracorporeal surfaces, anticoagulants are administered, including systemic heparin and local citrate. The differential and comparative effects of these anticoagulants on leukocyte function in acute kidney injury patients are, so far, insufficiently understood. In this bio-add-on-study, AKI patients were randomized as part of a parallel-group trial to either systemic heparin or regional citrate anticoagulation. Patient samples were collected upon inclusion, prior to CVVH initiation at day 0, day 1, day 3 and day 5, following CVVH initiation, and one day after cessation of CVVH, then immediately analyzed. Flow cytometric assessment of surface-receptor molecules was conducted. Whole-blood-perfused human microfluidic chambers were used for the analysis of neutrophil rolling and adhesion. Acute kidney injury was associated with significant changes in the surface expression of CD182 and CD16 throughout CVVH treatment, independent of the anticoagulation regime. AKI furthermore abrogated selectin-induced slow leukocyte rolling and diminished chemokine-induced leukocyte arrest. Subgroup analyses of citrate vs. heparin treatment showed no significant differences between groups, independent of the duration of CVVH treatment. CD182 and CD16 expression remained low in both groups throughout CVVH therapy. These data confirm that AKI impairs selectin-mediated leukocyte slow rolling and chemokine-induced leukocyte arrest in vitro. Systemic heparin or local citrate anticoagulation have no differential effect on the leukocyte recruitment steps examined in this study.

Combined Hemoperfusion and Continuous Veno-Venous Hemofiltration for Carbamazepine Intoxication

Introduction: Carbamazepine (CBZ) is a widely used anticonvulsant with a low molecular weight that allows for extracorporeal removal of free drug by both dialytic and hemoperfusion techniques, particularly in a massive overdose where serum protein binding is saturated. This report presents a case of CBZ intoxication where we were able to compare the mass removal of CBZ using hemoperfusion, with the mass removal of CBZ achieved with continuous renal replacement therapy (CRRT) during combined treatment. Methods: The Jafron HA230 resin hemoperfusion cartridge was applied in series with the continuous veno-venous hemofiltration (CVVH) circuit. Baseline and ongoing serum drug levels along with further samples from pre- and post-hemoperfusion cartridges and from CVVH effluent were collected. Results: Combined CVVH and resin hemoperfusion therapy in series was associated with a 50% reduction in the CBZ level from 16 mg/L to 8 mg/L over 3 h, far more rapid than that observed with CVVH alone or in the absence of extracorporeal drug clearance in the preceding hours. The combination therapy removed close to 35 mg/h of CBZ. Conclusion: The combination of CRRT and hemoperfusion can be easily deployed, appears safe, and is able to combine the CBZ mass removal achieved with each technique, thus to maximize CBZ extraction.

Effects of continuous venovenous hemofiltration on vancomycin trough concentrations in critically ill children.

BackgroundVancomycin trough concentrations are associated with clinical outcomes and drug adverse effects. This study investigates the effects of continuous venovenous hemofiltration (CVVH) on vancomycin trough concentrations in critically ill children with a vancomycin dosage of 40–60 mg/kg/day.MethodsChildren with steady-state vancomycin trough concentrations admitted to the pediatric intensive care unit (PICU) between January 2016 and December 2019 were retrospectively enrolled. Patients were divided into CVVH and non-CVVH groups according to treatment differences and renal function. Vancomycin trough concentrations were then compared between the groups, and risk factors for supratherapeutic trough concentrations (>20 mg/L) were analyzed with logistic regression.ResultsOf the 119 patients included, 35 were enrolled in the CVVH group and 84 in the non-CVVH group. Median vancomycin trough concentrations were significantly higher in the CVVH group than those in the non-CVVH group [14.9 (IQR =9.6–19.6) vs. 9.3 (IQR =7.0–13.4), P<0.001] and the proportion of therapeutic trough concentrations (10–20 mg/L) was similar between CVVH and non-CVVH groups (54.3% vs. 39.3%, P=0.133). However, CVVH therapy patients had a significantly higher proportion of supratherapeutic trough concentrations (20.0% vs. 1.2%, P=0.001) compared to the non-CVVH group. Multivariate analysis demonstrated that the Pediatric Risk of Mortality (PRISM) III score ≥28 (OR =13.7; 95% CI, 1.4–137.0; P=0.026] was an independent risk factor for supratherapeutic trough concentrations in critically ill patients.ConclusionsCVVH therapy affects vancomycin trough concentrations and is associated with supratherapeutic concentrations with a 40–60 mg/kg/day vancomycin dosage. PRISM III scores ≥28 may serve as an independent risk factor for supratherapeutic trough concentrations in children receiving CVVH therapy.

MON-PO633: Plasma Levels of Vitamins and Trace Elements are Low in Patients with Continuous Veno-Venous Hemofiltration Therapy and IV Double Vitamin and Triple Trace Element Supplementation is Safe. Results from the Meccias Trial

MON-PO633: Plasma Levels of Vitamins and Trace Elements are Low in Patients with Continuous Veno-Venous Hemofiltration Therapy and IV Double Vitamin and Triple Trace Element Supplementation is Safe. Results from the Meccias Trial

Effectiveness of continuous veno-venous hemofiltration in the treatment of severe acute pancreatitis.

Continuous veno-venous hemofiltration (CVVH) in the treatment of severe acute pancreatitis (SAP) was investigated. A total of 60 patients with SAP treated in Affiliated Dongtai Hospital of Nantong University from October 2015 to October 2017 were enrolled in this retrospective study. Among them, 32 patients received CVVH and routine internal medicine therapy (the CVVH group), and 28 received routine internal medicine therapy (the control group). Then biochemical indexes and severity of SAP after treatment were detected to investigate the roles of CVVH and routine internal medicine therapy in treating SAP. Inflammatory factors in both the CVVH and control groups were significantly decreased after treatment (P<0.05), and CVVH could eliminate more factors. Comparison of blood biochemical indexes between the CVVH and control groups were carried out. Significant improvement was found (P<0.05) after CVVH and routine internal medicine therapy. Besides, Acute Physiology and Chronic Health Evaluation (APACHE)-II grade was significantly decreased in the CVVH group compared with that in the control group after 7 days. CVVH therapy can effectively reduce the levels of inflammatory factors in SAP patients, improve their biochemical and physiological indicators, and have high clinical application value.

Effects of Changes in the Levels of Damage-Associated Molecular Patterns Following Continuous Veno-Venous Hemofiltration Therapy on Outcomes in Acute Kidney Injury Patients With Sepsis.

Background: We investigated the association of damage-associated molecular pattern (DAMP) removal with mortality in sepsis patients undergoing continuous veno–venous hemofiltration (CVVH).Methods: Circulating levels of DAMPs [mitochondrial DNA (mtDNA); nuclear DNA (nDNA); heat shock protein 70 (HSP70); and high mobility group box 1 (HMGB1)] and cytokines were measured at baseline, 6 and 12 h after initiation of CVVH. Urinary DNA levels were analyzed at baseline and end of CVVH. The expression of human leukocyte antigen (HLA)-DR was assayed at 0, 3, and 7 days after initiation of CVVH. Moreover, the effects of HSP70 and HMGB1 clearance on survival were analyzed.Results: We evaluated 43 patients with acute kidney injury (AKI) (33 sepsis patients). Twenty-two sepsis patients (67%) and three non-sepsis patients (30%) expired (P = 0.046). Significant reductions in the levels of circulating interleukin-6 (P = 0.046) and tumor necrosis factor-α (P = 0.008) were found in the sepsis group. The levels of mtDNA were increased (ND2, P = 0.035; D-loop, P = 0.003), whereas that of HSP70 was reduced (P = 0.000) in all patients during the first 12 h. The levels of DAMPs in the plasma were markedly increased after blood passage from the inlet through the dialyzer in survivor sepsis patients. The clearance rates of HSP70 and HMGB1 were good predictors of mortality [area under the curve (AUC) = 0.937, P = 0.000; AUC = 0.90, P = 0.001, respectively]. The level of HLA-DR was increased in response to higher HSP70 clearance (P = 0.006). Survival was significantly worse in groups with higher clearance rates of HSP70 and HMGB1 than the cut-off value (log-rank test: P = 0.000 for both). Higher HSP70 clearance was a significant independent predictor of mortality (odds ratio = 1.025, 95% confidence interval [CI]: 1.012–1.039, P = 0.000). The urinary nDNA (β-globin) level before CVVH was an independent risk factor for the duration of CVVH in patients with sepsis (sRE = 0.460, 95% CI: 1.720–8.857, P = 0.005).Conclusion: CVVH removes inflammatory factors, reduces urinary DAMPs, and removes plasma DAMPs. However, survival decreases in response to higher HSP70 clearance.

Continuous blood purification treatment for endotoxin-induced acute respiratory distress syndrome.

This study aimed to explore the effects of continuous blood purification (CBP) treatment in pigs affected with acute respiratory distress syndrome (ARDS). A total of 12 healthy male pigs, weighing 12±1.8 kg, were randomly and equally assigned to the control and experimental groups. The ARDS pig model was prepared by intravenous injections of endotoxin (20 µg/kg). The control group was given conventional supportive therapy, while the experimental group was given continuous veno-venous hemofiltration therapy. During the treatment process, the variations in dynamic lung compliance, oxygenation index, hemodynamics, and urine volume per hour at different times (Baseline, 0, 2, 4, and 6 h) were recorded. The levels of tumor necrosis factor (TNF-α), interleukin 6 (IL-6), and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were measured using the enzyme-linked immunosorbent assay. The histomorphological changes of the lung, heart, and kidney were visualized using a light microscope. The nuclear factor κB p65 protein content of the heart, lung, and kidney tissues was also detected using western blot. The experimental group outperformed the control group in both respiratory and hemodynamic events. CBP treatment cleared TNF-α, IL-6, and IL-10 partially from serum and BALF. The pathological examination of the heart, lung, and kidney tissues revealed that the injury was less severe in the experimental group. CBP treatment can improve the organ functions of pigs affected with endotoxin-induced ARDS and protect these organs to some extent.

Safety and Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study.

To assess the safety and efficacy of combining extracorporeal CO2 removal with continuous renal replacement therapy in patients presenting with acute respiratory distress syndrome and acute kidney injury. Prospective human observational study. Patients received volume-controlled mechanical ventilation according to the acute respiratory distress syndrome net protocol. Continuous venovenous hemofiltration therapy was titrated to maintain maximum blood flow and an effluent flow of 45 mL/kg/h with 33% predilution. Eleven patients presenting with both acute respiratory distress syndrome and acute kidney injury required renal replacement therapy. A membrane oxygenator (0.65 m) was inserted within the hemofiltration circuit, either upstream (n = 7) or downstream (n = 5) of the hemofilter. Baseline corresponded to tidal volume 6 mL/kg of predicted body weight without extracorporeal CO2 removal. The primary endpoint was 20% reduction in PaCO2 at 20 minutes after extracorporeal CO2 removal initiation. Tidal volume was subsequently reduced to 4 mL/kg for the remaining 72 hours. Twelve combined therapies were conducted in the 11 patients. Age was 70 ± 9 years, Simplified Acute Physiology Score II was 69 ± 13, Sequential Organ Failure Assessment score was 14 ± 4, lung injury score was 3 ± 0.5, and PaO2/FIO2 was 135 ± 41. Adding extracorporeal CO2 removal at tidal volume 6 mL/kg decreased PaCO2 by 21% (95% CI, 17-25%), from 47 ± 11 to 37 ± 8 Torr (p < 0.001). Lowering tidal volume to 4 mL/kg reduced minute ventilation from 7.8 ± 1.5 to 5.2 ± 1.1 L/min and plateau pressure from 25 ± 4 to 21 ± 3 cm H2O and raised PaCO2 from 37 ± 8 to 48 ± 10 Torr (all p < 0.001). On an average of both positions, the oxygenator's blood flow was 410 ± 30 mL/min and the CO2 removal rate was 83 ± 20 mL/min. The oxygenator blood flow (p <0.001) and the CO2 removal rate (p = 0.083) were higher when the membrane oxygenator was placed upstream of the hemofilter. There was no safety concern. Combining extracorporeal CO2 removal and continuous venovenous hemofiltration in patients with acute respiratory distress syndrome and acute kidney injury is safe and allows efficient blood purification together with enhanced lung protective ventilation.

Intraoperative Continuous Veno-Venous Hemofiltration Facilitates Surgery in Liver Transplant Patients With Acute Renal Failure

IntroductionWe have aggressively used continuous veno-venous hemofiltration (CVVH) on high model for end-stage liver disease (MELD) score liver transplant patients with acute kidney injury and hypothesized that the addition of intraoperative CVVH therapy would improve overall outcomes. MethodsWe performed a retrospective review of all adult, single organ, liver transplant recipients requiring preoperative renal replacement therapy between January 1, 2011 and June 1, 2013. Intraoperative and perioperative records and laboratory values were collected and used to create a database of these patients. Patients were grouped according to whether or not they underwent CVVH at the time of liver transplantation. ResultsTwenty-one patients with new-onset renal failure requiring preoperative renal replacement therapy received a liver transplant alone. Fourteen received intraoperative CVVH and 7 patients did not. The average MELD score was similar between groups (34 for intraoperative CVVH vs 35; P = .8). Preoperative sodium and potassium were higher for the group receiving intraoperative CVVH, but still fell within normal ranges. Preoperative lactate levels were higher in the group that received intraoperative CVVH (4.7 vs 2.0 mmol/L; P = .01). Intraoperative CVVH did not decrease intraoperative transfusion requirements or intensive care unit (ICU) and hospital lengths of stay. Differences in reoperative rates did not reach statistical significance. All patients were weaned off renal replacement therapy. One-year patient survival rate was 86% for intraoperative CVVH versus 71% without. ConclusionThe judicious use of intraoperative CVVH therapy may permit patients with increasing severity of illness to achieve outcomes comparable with less ill patients.

Intraoperative Continuous Veno-Venous Hemofiltration Facilitates Surgery in Liver Transplant Patients With Acute Renal Failure.

We have aggressively utilized continuous veno-venous hemofiltration (CVVH) on high MELD liver transplant patients with acute kidney injury in an effort to decrease transfusion requirements and complications, and improve overall outcomes. Methods: We performed a retrospective review of all adult, single organ, liver transplant recipients requiring pre-operative renal replacement therapy between 2011 and 2013. Intra- and peri-operative records were collected to create a database of these patients. Patients were grouped according to whether or not they underwent CVVH at the time of liver transplant. Results: Twenty-one 21 patients requiring CVVH received a liver transplant alone. Of these 21 patients, 14 received intraoperative CVVH and 7 patients did not. The average MELD score was similar between groups (34 for CVVH vs. 35, p=0.8). Pre-operative sodium and potassium were higher for the group receiving CVVH (p<0.01, p=0.02) but still fell within normal ranges. Pre-operative lactate levels were higher in the group that received intraoperative CVVH (4.7 vs. 2.0 mmol/L (p=0.01)). Intraoperative CVVH did not decrease intraoperative transfusion requirements (16 vs. 20 units PRBC, p=0.6; 17 vs. 19 units FFP, p=0.7; 8 vs. 16 units platelets, p=0.2), post-operative acidosis (7.40 vs. 7.35, p=0.8), or ICU and hospital lengths of stay. Furthermore, post-operative day 1 transfusion requirements were not decreased by intraoperative CVVH, (3 vs. 2 units PRBC, p=0.4; 2 vs. 1 unit FFP, p=0.2; 0.8 vs. 0.4 units platelets, p=0.4). Differences in reoperative rates did not reach statistical significance (29% with CVVH vs. 50%, p=0.6.) All patients were weaned off renal replacement therapy. Rolling one-year patient and graft survival was 100% for intraoperative CVVH versus 71% without, but this was not statistically significant (p=0.2). Conclusions: Patients undergoing intraoperative CVVH achieved statistically equivalent survival and transfusion outcomes despite higher pre-operative sodium, potassium, and lactate values, with trends of higher survival and decreased re-operative rates. The judicious use of intraoperative CVVH therapy may permit patients with increasing severity of illness to achieve outcomes comparable to less ill patients; however, aggressive pre- and post-operative CVVH may diminish the effect of intraoperative CVVH in cases with relatively short operative times.

Continuous Veno-Venous Hemofiltration for Massive Rhabdomyolysis After Malignant Hyperthermia: Report of 2 Cases

We present 2 cases of fulminant malignant hyperthermia (MH), complicated with massive rhabdomyolysis. The patients were successfully treated in the intensive care unit of our university teaching hospital, despite the lack of availability of dantrolene in our country, by early application of continuous veno-venous hemofiltration (CVVH). Both male patients developed fulminant malignant hyperthermia during anesthesia for oromaxillofacial surgery. CVVH was employed when the values of creatine phosphokinase (CPK), myoglobin (Mb), and lactate dehydrogenase (LDH) increased significantly. After emergency treatment and CVVH therapy, the values of CPK, Mb, and LDH in the blood plasma of the patients decreased significantly. The complications, including acute renal failure, disseminated intravascular coagulation, and acute respiratory distress syndrome were also treated without any obvious organ damage. Early detection and management are the keys to treat MH successfully. CVVH is a valuable therapeutic application in the initial/critical management of severe rhabdomyolysis. If these complications occur even with initial treatment with dantrolene, our experiences may be useful adjunctive treatments to consider.

Hypophosphatemia during continuous veno-venous hemofiltration is associated with mortality in critically ill patients with acute kidney injury

IntroductionThe primary aim of this study was to determine whether hypophosphatemia during continuous veno-venous hemofiltration (CVVH) is associated with the global outcome of critically ill patients with acute kidney injury (AKI).Methods760 patients diagnosed with AKI and had received CVVH therapy were retrospectively recruited. Death during the 28-day period and survival at 28 days after initiation of CVVH were used as endpoints. Demographic and clinical data including serum phosphorus levels were recorded along with clinical outcome. Hypophosphatemia was defined according to the colorimetric method as serum phosphorus levels < 0.81 mmol/L (2.5 mg/dL), and severe hypophosphatemia was defined as serum phosphorus levels < 0.32 mmol/L (1 mg/dL). The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was calculated to reflect the persistence of hypophosphatemia.ResultsThe Cox proportional hazard survival model analysis indicated that the incidence of hypophosphatemia or even severe hypophosphatemia was not associated with 28-day mortality independently (p = 0.700). Further analysis with the sub-cohort of patients who had developed hypophosphatemia during the CVVH therapy period indicated that the mean ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was 0.58, and the ratio independently associated with the global outcome. Compared with the patients with low ratio (< 0.58), those with high ratio (≥ 0.58) conferred a 1.451-fold increase in 28-day mortality rate (95% CI 1.103–1.910, p = 0.008).ConclusionsHypophosphatemia during CVVH associated with the global clinical outcome of critically ill patients with AKI. The ratio of CVVH therapy days with hypophosphatemia over total CVVH therapy days was independently associated with the 28-day mortality, and high ratio conferred higher mortality rate.

Coupled Plasma Filtration Adsorption Combined With Continuous Veno-venous Hemofiltration Treatment in Patients With Severe Acute Pancreatitis

Severe acute pancreatitis (SAP) still has a high mortality rate. Coupled plasma filtration adsorption (CPFA) and continuous veno-venous hemofiltration (CVVH) are 2 extracorporeal blood purification techniques. We hypothesized that CPFA combined with CVVH could preferentially improve prognosis and suppress clinical manifestations of SAP. In this observational cohort study, 25 patients with SAP were enrolled, in which 12 received CPFA plus CVVH treatment (group 1), and 13 received CVVH therapy (group 2). All the patients underwent a successive 10-day intervention. Clinical indicators were detected before or after the intervention and the results were compared between the 2 groups. The feasibility and the survival rate were evaluated on day 28. Compared with group 2, oxygenation index (PaO(2)/FiO(2)), mean arterial pressure, serum amylase, and blood urine nitrogen showed significant differences (all P<0.01) and serum TNF-α, IL-1β, IL-6 were reduced and IL-10 was elevated with time in group 1 (all P<0.01). Liver functions, electrolyte, and acid-base balance did not show significant difference before and after the 10-day treatment with CPFA plus CVVH compared with CVVH (P>0.05). No therapy-related adverse reactions were noted in both groups. Twenty-eight-day survival rate of group 1 was higher than that in group 2 [91.7% (11/12) vs. 53.8% (7/13), P<0.05]. CPFA combined with CVVH was an effective and safe method for treatment of SAP patients, the mechanism being related to its effect on regulating the level of cytokines and serum amylase.

Regarding “Late Initiation of Continuous Venovenous Hemofiltration Therapy is Associated with a Lower Survival Rate in Surgical Critically Ill Patients with Postoperative Acute Kidney Injury”

Regarding “Late Initiation of Continuous Venovenous Hemofiltration Therapy is Associated with a Lower Survival Rate in Surgical Critically Ill Patients with Postoperative Acute Kidney Injury”

Effect of continuous veno-venous hemofiltration on the peripheral blood levels of high mobility group box chromosomal protein 1 in patients with systemic inflammatory response syndrome or sepsis

Objective To investigate the effect of continuous veno-venous hemofiltration (CVVH) on the peripheral blood levels of high mobility group box chromosomal protein 1 (HMGB-1) in patients with systemic inflammatory response syndrome (SIRS) or sepsis.Methods Thirty patients with SIRS or sepsis in Intensive Care Unit of our hospital were scheduled for treatment of CVVH.The replacement liquid was put in by the pattern of pre-dilution of 40％ and post-dilution of 60％.The flow-rate was 3 L/h.The blood flow-rate was from 200 to 300 ml/min.5 ml blood from right radial artery was got at the time points of preCVVH,CVVH 2 h,6 h,8 h and post-CVVH 12 h and the serum was stored at the temperature of-20 ℃ after high speed centrifugation,and 2 ml filter liquor was reserved at the time point of CVVH 6 h.The concentration of serum and filter liquor HMGB-1 was measured by ELISA,but that of TNF-α and IL-6 were measured by radioimmunity.Results 30 patients adept CVVH therapy within 24 h to the hospital,and their therapy time was 2 ～ 5(2.4 ± 1.5) d.Among them,17 cases survived and 13 cases died with a fatality rate of 43.3％.Serum concentration of HMGB-1 decreased from the baseline in patients,although this decrease was not statistically significant[(11.88 ± 6.06) ng/ml,(11.97 ± 5.66) ng/ml,(11.94 ± 5.94) ng/ml,(11.73 ± 5.19) ng/ml vs (13.87 ± 4.68) ng/ml,P ＞ 0.05],Serum concentration of both TNF-αand IL-6 after therapy significantly decreased compared to the baseline in patients [TNF-α: (0.28 ± 0.15)ng/ml,(0.30 ± 0.14) ng/ml,(0.29 ± 0.19) ng/ml,(0.33 ± 0.19) ng/ml vs (0.41 ± 0.12) ng/ml,IL-6:(408.20 ±92.18)pg/ml,(250.51 ± 107.34)pg/ml,(276.00 ± 126.20) pg/ml,(315.16 ± 130.97) pg/ml vs (513.35 ± 125.95) pg/ml,P ＜ 0.05].Conclusions CVVH could decrease the concentration of HMGB-1 in peripheral blood,which would be one of the mechanisms of action for CVVH on sepsis. Key words: Systemic inflammatory response syndrome/therapy; Sepsis/therapy; High mobility group proteins/blood; Hemofiltration

Effect of Continuous Venovenous Hemofiltration Dose on Achievement of Adequate Vancomycin Trough Concentrations

The vancomycin dose necessary for the achievement of target serum trough concentrations during continuous venovenous hemofiltration (CVVH) remains to be elucidated. This was a retrospective cohort study of critically ill adults at a tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010 with a steady-state vancomycin trough concentration. The 87 included patients were grouped according to low (≤30 ml/kg/h; n = 10) or high (>30 ml/kg/h; n = 77) CVVH hemofiltration rate (HFR) for analysis. Vancomycin goal trough achievement occurred in only 32 (37%) patients. The primary endpoint of trough attainment significantly differed between HFR subgroups: 90% versus 30% in low- and high-HFR individuals, respectively (P < 0.001). Patients with subtherapeutic trough concentrations had a median (interquartile range) HFR of 40 ml/kg/h (range, 37 to 47 ml/kg/h) compared to 36 ml/kg/h (range, 30 to 39 ml/kg/h) in those who achieved the trough goal. Irrespective of goal trough, an inverse correlation existed between HFR and serum vancomycin concentration (r = -0.423; P < 0.001). In the subgroup of 14 methicillin-resistant Staphylococcus aureus (MRSA) patients, trough achievement was similar to the aggregate cohort (36%). Mortality at 28 days was unrelated to trough achievement in both the overall sample (P = 0.516) and in culture-positive MRSA patients (P = 0.396). Critically ill patients undergoing CVVH therapy may experience clinically significant reductions in goal vancomycin troughs. The results of the present study justify prospective evaluations in this population to determine the optimal vancomycin dosing strategy for attainment of goal trough concentrations.

Late Initiation of Continuous Veno-Venous Hemofiltration Therapy is Associated with a Lower Survival Rate in Surgical Critically Ill Patients with Postoperative Acute Kidney Injury

There is controversy about the appropriate timing for renal replacement therapy in patients with acute kidney injury (AKI). We are interested in the appropriate timing for initiation of continuous renal replacement therapy in critically ill surgical patients with postoperative acute kidney injury. Seventy-three critically ill surgical patients with postoperative AKI who received continuous renal replacement therapy (CRRT) were enrolled. Indications for CRRT were: 1) AKI with hyperkalemia, 2) metabolic acidosis, 3) pulmonary edema refractory to diuretics, and 4) oliguria with progressive azotemia, especially in unstable hemodynamics. Using RIFLE (Risk, Injury, Failure, Loss, End stage) classification, patients who received CRRT in the “Risk” stage were defined as early group, whereas those in the “Injury/ Failure” stage were labeled as late group. We used continuous veno-venous hemofiltration as CRRT in this series. There were 20 patients in the early group and 53 patients in the late group. The mean ages were 61.5 ± 21.8 years versus 60.8 ± 17.5 years. The mortality rate was 50 per cent versus 84.9 per cent. There were no significant differences in demographic characteristics or type of surgery or physiological scores. Our data show that late initiation of CRRT is associated with a lower survival rate in critically ill surgical patients with postoperative AKI; however, further studies are required.

Once-Daily Amikacin Dosing in Burn Patients Treated with Continuous Venovenous Hemofiltration

Amikacin clearance can be increased in burn injury, which is often complicated by renal insufficiency. Little is known about the impact of renal replacement therapies, such as continuous venovenous hemofiltration (CVVH), on amikacin pharmacokinetics. We retrospectively examined the clinical pharmacokinetics, bacteriology, and clinical outcomes of 60 burn patients given 15 mg/kg of body weight of amikacin in single daily doses. Twelve were treated with concurrent CVVH therapy, and 48 were not. The pharmacodynamic target of ≥10 for the maximum concentration of drug in serum divided by the MIC (C(max)/MIC) was achieved in only 8.5% of patients, with a small reduction of C(max) in patients receiving CVVH and no difference in amikacin clearance. Mortality and burn size were greater in patients who received CVVH. Overall, 172 Gram-negative isolates were recovered from the blood cultures of 39 patients, with amikacin MIC data available for 82 isolates from 24 patients. A 10,000-patient Monte Carlo simulation was conducted incorporating pharmacokinetic and MIC data from these patients. The cumulative fraction of response (CFR) was similar in CVVH and non-CVVH patients. The CFR rates were not significantly improved by a theoretical 20 mg/kg amikacin dose. Overall, CVVH did not appear to have a major impact on amikacin serum concentrations. The low pharmacodynamic target attainment appears to be primarily due to higher amikacin MICs rather than more rapid clearance of amikacin related to CVVH therapy.

Effect of continuous blood purification on endothelial cell function in patients with severe sepsis

To investigate the effect of continuous blood purification (CBP) in patients with severe sepsis, and to evaluate the change in endothelial cell function in patients with severe sepsis during CBP therapy. According to random principle, 45 patients were divided into control group (n=22) and CBP group (n=23). All patients of both groups received routine treatment according to international guidelines 2008 for management of severe sepsis, but the patients in the CBP group also received continuous veno-venous hemofiltration (CVVH) for 72 hours, the ultrafiltrate volume was 40 ml×kg(-1)×h(-1). Blood gas analysis was done before and 24 hours and 72 hours after CVVH therapy. The activated protein C (APC), soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor (vWF) were measured. Also the length of stay in intensive care unit (ICU), time of mechanical ventilation, and death rate of patients in 28 days were observed. Compared with control group, the length of stay in ICU (days) and length of use of ventilator (days) in CBP group were shorter (9.12±3.07 vs. 11.64±4.82, 5.52±3.48 vs. 8.02±5.25, both P<0.05), and the death rate in 28 days was lower [13.0% (3/23) vs. 40.9% (9/22), P<0.05]. After therapy, patients in CBP group showed more reduction in the APACHEII score compared with control group (3.96±4.07 vs. 1.68±2.43, P<0.05). Patients in control group showed less change in APC, sICAM-1 and vWF. APC in CBP group increased at 72 hours, and sICAM-1 and vWF of CBP group respectively decreased at 24 hours or 72 hours, while the APC (μg/L) and vWF (mg/L) at 72 hours showed significant change compared with that of the control group (15.12±7.57 vs. 10.01±5.83, 1.58±0.73 vs. 2.64±1.34, P<0.05 and P<0.01). In patients who died in 28 days (12 patients) there were little changes in APC, sICAM-1 and vWF, while patients who lived for 28 days (33 patients), showed significantly more reduction in sICAM-1 (μg/L) and vWF (mg/L, 61.03±45.58 vs. 104.64±71.08, 1.88±1.21 vs. 2.70±0.95,both P<0.05). The APC value (μg/L) was increased after treatment in patients who survived for 28 days (13.55±7.11 vs. 10.37±7.60, P<0.01). CBP therapy can protect endothelial cell function and ameliorate dysfunction, and it reduces the severity of the severe sepsis as well as improves the outcome of patients with severe sepsis.

Continuous hemofiltration in the control of neonatal hyperammonemia: a 10-year experience

In a 10-year review of the utilization of continuous veno-venous hemofiltration (CVVH) for the treatment of neonatal hyperammonemia, 14 patients were identified with hyperammonemia due to either a urea cycle defect or an organic acidemia. Intensive care survival was 64%. The pretreatment level of serum ammonia and the rapidity of ammonia clearance did not differ between survivors and non-survivors (p = 0.16 and p = 0.93, respectively). Likewise, the duration of CVVH therapy did not differ between survivors and non-survivors (p = 0.1). Indicators of pretreatment physiological stress showed either a correlation with non-survival [Pediatric Risk of Mortality (PRISM) score, p = 0.006, cardioactive drug requirement, p = 0.003], or demonstrated a trend to such a correlation (serum lactate, p = 0.06). Complications associated with the CVVH technique were infrequent. Hypotension was seen in seven patients, but in only one patient did it arise de novo following the initiation of CVVH. In conclusion, neither the severity of the hyperammonemic state nor the efficacy of ammonia removal correlated with patient outcome. The pre-CVVH PRISM score and requirement for cardio-active medication were significantly greater in those patients who did not survive their acute illness. The pre-CVVH physiological condition of the neonates in this cohort was the main determinant of outcome.