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.     

Treatment of critically ill children with kidney injury by sustained low-efficiency daily diafiltration

Background

Continuous renal replacement therapy (CRRT) and intermittent hemodialysis (IHD) offer diverse benefits and drawbacks for critically ill children with acute kidney injury (AKI). Sustained low-efficiency daily diafiltration (SLEDD-f) involves a conceptual and technical hybrid of CRRT and IHD. We report our SLEDD-f application to critically ill children in the pediatric intensive care unit (PICU).

Methods

SLEDD-f was delivered by the new Fresenius 5008 therapy system with blood flow 5?ml/kg/min, dialysate flow 260?ml/min, hemofiltration 35?ml/kg/h for 8–10?h daily. Changes in blood pressure, blood gas, electrolyte, hemoglobulin (Hb), and hematocrit (Hct) were closely monitored.

Results

From February 2010 to June 2011, 14 critical patients with a total of 60 SLEDD-f sessions were studied retrospectively. Heparin was used in 46 sessions (76.6%) with no bleeding complications. Hypertension above 135?mmHg returned to normal, hypotension below 90?mmHg showed no drop. Metabolic acidosis and hyperkalemia normalized. Elevated Hb, Hct, and their ratio revealed improving hemodilution. Three episodes of intradialytic hypotension (5.0%) and one of circuit clotting (1.7%) led to premature termination. The 28-day survival rate was 71.4%.

Conclusions

This pilot investigation demonstrates that SLEDD-f provides good hemodynamic tolerance and correction of fluid overload, pH, and electrolyte imbalance for critically ill children with AKI.     

Anti‐gal antibodies in α1,3‐galactosyltransferase gene‐knockout pigs

Fang J, Walters A, Hara H, Long C, Yeh P, Ayares D, Cooper DKC, Bianchi J. Anti‐gal antibodies in α1,3‐galactosyltransferase gene‐knockout pigs. Xenotransplantation 2012; 19: 305–310. © 2012 John Wiley & Sons A/S. Abstract Serum anti‐galactose‐α1,3‐galactose (Gal) IgM and IgG antibody levels were measured by ELISA in α1,3‐galactosyltransferase gene‐knockout (GTKO) pigs (78 estimations in 47 pigs). A low level of anti‐Gal IgM was present soon after birth, and rose to a peak at 4–6 m, which was maintained thereafter even in the oldest pigs tested (at >2 yr). Anti‐Gal IgG was also present at birth, peaked at 3 m, and after 6 m steadily decreased until almost undetectable at 20 m. No differences in this pattern were seen between pigs of different gender. Total IgM followed a similar pattern as anti‐Gal IgM, but total IgG did not decrease after 6m. The data provide useful baseline data for future experimental studies in GTKO pigs, e.g., relating to the antibody response to WT pig allografts.     

Inhibition of nitric oxide can ameliorate apoptosis and modulate matrix protein gene expression in bacteria infected chondrocytes in vitro.

Bacterial infection stimulates nitric oxide (NO) production in chondrocytes. However, the role of NO in chondrocyte apoptosis after infection remains unclear. The purpose of the study was to test if inhibition of NO could ameliorate apoptosis and modulate matrix protein gene expression in bacteria-infected chondrocytes. It was shown that pre-treating chondrocytes with L-NAME (1 mM) significantly decreased the release of NO (from 72 to 14 microM) and the extent of apoptosis (from 52.9% to 18.9%). Pre-treatment with L-NAME also counteracted the bacteria-induced downregulation of Type II collagen (from 26% to 79%) and aggrecan (from 63% to 105%) mRNA levels. Inhibition of NO after the induction of infection could not decrease the extent of apoptosis and modulate matrix protein gene expression. The results of this study support the hypothesis that NO has an important role in bacteria-induced chondrocyte apoptosis. Pre-treatment but not post-treatment could ameliorate the extent of apoptosis and reestablish the cartilage matrix protein gene expression. This study suggests that in addition to NO, other mechanisms may be responsible for the sustained destruction of articular cartilage in the post-infectious arthropathy.     

Preincisional dextromethorphan combined with thoracic epidural anesthesia and analgesia improves postoperative pain and bowel function in patients undergoing colonic surgery

Colonic surgery is associated with severe postoperative pain and postoperative ileus, which contribute to delayed hospital discharge. In previous studies, we demonstrated that IM dextromethorphan (DM) provided preemptive analgesia and improved postoperative pain. The benefit of thoracic epidural anesthesia (TEA) and postoperative epidural analgesia on postoperative pain was well demonstrated. The goal of this study was to investigate the effect of preincisional IM DM combined with intraoperative TEA and postoperative patient-controlled epidural analgesia (PCEA) on pain and bowel function after colonic surgery. Patients were randomized into 3 equal groups to receive: 1) chlorpheniramine maleate (CPM) 20 mg and general anesthesia (CPM-GA); 2) CPM 20 mg and GA combined with TEA (CPM-TEA); or 3) DM 40 mg (containing 20 mg of CPM) and GA combined with TEA (DM-TEA). The CPM, DM, and TEA with lidocaine were administered after GA induction via an IM injection and 30 min before the skin incision. All patients received postoperative PCEA for pain control. Analgesic effects were evaluated for 72 h after surgery using visual analog scale pain scores at rest and moving, time to first PCEA request for pain relief, total PCEA consumption, and the time to first passage of flatus. Statistically significant improvement of postoperative pain and bowel function was observed in the following order: DM-TEA > CPM-TEA > CPM-GA. Compared with the CPM-TEA group, the DM-TEA group averaged 1.6 points lower on first-hour pain scores, 40 min longer to first PCEA request, 15.8 mL less PCEA drug over 72 h, and 14.7 h earlier bowel function (all P < 0.01). We conclude that the combination of preincisional DM (40 mg IM), intraoperative TEA, and postoperative PCEA enhances analgesia and facilitates recovery of bowel function, suggesting possible synergistic interaction with local anesthetics and opioids.     

The Effects of Exogenous Administration of Human Coagulation Factors Following Pig‐to‐Baboon Liver Xenotransplantation

We sought to determine the effects of exogenous administration of human coagulation factors following pig‐to‐baboon liver xenotransplantation (LXT) using GalT‐KO swine donors. After LXT, baboons received no coagulation factors (historical control, n = 1), bolus administration of a human prothrombin concentrate complex (hPCC; 2.5 mL/kg, n = 2), continuous infusion of hPCC (1.0 mL/h, n = 1) or continuous infusion of human recombinant factor VIIa (1 µg/kg per hour, n = 3). The historical control recipient demonstrated persistent thrombocytopenia despite platelet administration after transplant, along with widespread thrombotic microangiopathy (TMA). In contrast, platelet levels were maintained in bolus hPCC recipients; however, these animals quickly developed large‐vessel thrombosis and TMA, leading to graft failure with shortened survival. Recipients of continuous coagulation factor administration experienced either stabilization or an increase in their circulating platelets with escalating doses. Furthermore, transfusion requirements were decreased, and hepatic TMA was noticeably absent in recipients of continuous coagulation factor infusions compared with the historical control and bolus hPCC recipients. This effect was most profound with a continuous, escalating dose of factor VIIa. Further studies are warranted because this regimen may allow for prolonged survival following LXT.     

Effects of temperature on radiochemical purity and immunoreactivity of radiolabeled monoclonal antibody 1H10

OBJECTIVE: This study was undertaken to investigate the effects of temperature on preserving the radiochemical purity and immunoreactivity of 125I- and 131I-labeled monoclonal antibody (MAb) 1H10--an antibody against human cervical carcinoma cell-surface antigen. METHODS: An antibody-irrelevant human melanoma cell line, H2269, served as the control group. Iodine-125 and 131I radiolabeling of MAbs 1H10 and H2669 was performed by the chloramine-T method. All the prepared MAbs were divided into aliquots and stored at 4, -20, and -70 degrees C for 2-14 d. The radiochemical purity and immunoreactivity of the labeled antibodies in set conditions were measured by thin-layer chromatography and a modified index, respectively, after a single freeze-and-thaw cycle. RESULTS: Reduced release of free radioiodide and better preservation of immunoreactivity were observed in the radiolabeled MAbs stored at -70 degrees C than in those stored at -20 degrees C or 4 degrees C. The extent of free iodide dissociation and immunologic binding degradation of 125I-labeled MAb 1H10 appeared milder than that of 131I-labeled MAb under the same conditions. However, both 125I- and 131I-labeled MAb stored at -70 degrees C or -20 degrees C retained more than 90% radiochemical purity for at least 3d. CONCLUSION: Freezing provides an appropriate alternative for reducing radiolysis and preserving immunoreactivity of radioiodinated MAbs. MAb 1H10, labeled with either 125I or 131I and stored at temperatures of -20 degrees C or below for 3 d after labeling, appeared stable in both radiolabeling and binding studies in vitro and was still acceptable for in vivo use.     

Simultaneous combined use of flexible ureteroscopy and percutaneous nephrolithotomy to reduce the number of access tracts in the management of complex renal calculi

OBJECTIVE: To present early experience in managing complex renal calculi using a combined ureteroscopic and percutaneous approach, as complex and branched renal calculi often require multiple access tracts during percutaneous nephrolithotomy (PNL), and the combined use of flexible ureteroscopy and PNL has the potential to reduce the inherent morbidity of several tracts. PATIENTS AND METHODS: The study included seven patients (mean age 54 years) with multiple, branched, large-volume renal calculi suitable for management with PNL. Preoperative data, including patient demographics, stone location and stone surface area, were recorded. After informed consent, the patients underwent combined PNL and ureteroscopy in one session. Intraoperative data, including the location of PNL puncture sites, operative duration and complications, were analysed. Stone-free rates were determined by follow-up imaging at 3 months. RESULTS: All patients had either two or more stones in separate locations in the collecting system, or staghorn stones involving multiple calyces. The mean stone burden was 666 mm(2). All patients had only one percutaneous access tract. The mean operative duration was 142 min and the mean blood loss 79 mL. Two patients had small residual stones (< 3 mm), that required ureteroscopic intervention as they failed to pass spontaneously by 3 months after the initial combined procedure. The convalescence was similar to that in our current PNL practice; imaging showed that five of the patients were stone-free. CONCLUSIONS: Combined PNL and ureteroscopic management can effectively reduce the number of percutaneous access tracts which would otherwise be required for managing complex and branched renal calculi, as stones in an unfavourable location relative to the access tract can be relocated and fragmented within easy reach of the single nephrostomy tract. This manoeuvre reduces potential patient morbidity and blood loss but with no significant effect on stone-free rates and operative durations.     

Effects of the Antioxidants Lycium Barbarum and Ascorbic Acid on Reperfusion Liver Injury in Rats

Objective

Ischemia/reperfusion (I/R) of the rat liver can induce liver injury through mechanisms involving oxidative and nitrosative stresses. In this study we examined the effects of antioxidants Lycium barbarum (LB) and ascorbic acid on I/R-induced liver injury in rats.

Methods

Liver ischemia was induced by clamping the common hepatic artery and portal vein of rats for 40 minutes. Thereafter, flow was restored with reperfusion for 90 minutes. Blood samples collected before ischemia and after reperfusion were analyzed for alanine transaminase (ALT), lactic dehydrogenase (LDH), hydroxyl radical, and nitric oxide (NO) levels. Pharmacologic interventions included administration of ascorbic acid (100 mg/kg, i.p., 1 hour before I/R) or LB, an extract of Gogi berries: 600 mg in 100 mL of drinking water for 2 weeks prior to experimentation.

Results

This protocol resulted in elevation of blood concentrations of NO, hydroxyl radical, ALT, and LDH (P < .001) in the I/R-induced liver injury group. Ascorbic acid significantly attenuated the reperfusion liver injury by attenuating hydroxyl radical (P < .01) and NO (P < .05) release. The LB aggravated I/R-induced liver injury by increasing hydroxyl radical release with no effect on NO release.

Discussion and conclusions

This I/R protocol resulted in oxidative and nitrosative stress and liver injury. Ascorbic acid showed significant protective effects on reperfusion liver injury by attenuating hydroxyl radical and NO release. In contrast, LB aggravated liver injury by increasing hydroxyl radical release.     

Inducible nitric oxide synthase expressions in different lung injury models and the protective effect of aminoguanidine

OBJECTIVE: Our aim was to study the expression of inducible nitric oxide synthase (iNOS) in 2 experimental models: (1) ischemia/reperfusion (I/R) of the lung tissues and (2) oleic acid infusion. The protective effect of an iNOS inhibitor, aminoguanidine, was evaluated in these 2 injury models. MATERIALS AND METHODS: Real-time polymerase chain reactions and Western blots were used to assess the mRNA and protein expressions of iNOS in lung tissues after applying 2 injury models. In the I/R model, ischemia was induced by clamping one branch of the pulmonary artery for 60 minutes and then reperfusing for 120 minutes. In the bone fracture model, lung injury was induced by intravenous (IV) infusion of oleic acid (0.1 mL/kg); analysis was performed 6 hours after injury. Blood samples were collected for the assay of 3 inflammatory parameters: tumor necrosis factor alpha, hydroxyl radicals, and nitric oxide (NO). The wet/dry lung weight ratio was used as a parameter reflecting the lung injury level. RESULTS: mRNA and protein expressions of iNOS were significantly increased in these 2 lung injury models compared with the controls. Blood concentrations of TNFalpha, hydroxyl radicals, NO, and wet/dry lung weight ratio were also significantly higher in the 2 experimental groups than in the sham-treated group. The iNOS inhibitor aminoguanidine (20 mg/kg) significantly attenuated the lung injury induced by these challenges. CONCLUSIONS: Reperfusion of the ischemic lung tissues or IV infusion of oleic acid can both induce lung injury by activating systemic inflammatory responses and inducing iNOS expression. Administration of aminoguanidine can significantly attenuate the injury, suggesting that iNOS expression may play a critical role in the lung injury induced in these 2 models.