Balanced Multielectrolyte Solution versus Saline in Critically Ill Adults.

BACKGROUND: Whether the use of balanced multielectrolyte solution (BMES) in preference to 0.9% sodium chloride solution (saline) in critically ill patients reduces the risk of acute kidney injury or death is uncertain. METHODS: In a double-blind, randomized, controlled trial, we assigned critically ill patients to receive BMES (Plasma-Lyte 148) or saline as fluid therapy in the intensive care unit (ICU) for 90 days. The primary outcome was death from any cause within 90 days after randomization. Secondary outcomes were receipt of new renal-replacement therapy and the maximum increase in the creatinine level during ICU stay. RESULTS: A total of 5037 patients were recruited from 53 ICUs in Australia and New Zealand - 2515 patients were assigned to the BMES group and 2522 to the saline group. Death within 90 days after randomization occurred in 530 of 2433 patients (21.8%) in the BMES group and in 530 of 2413 patients (22.0%) in the saline group, for a difference of -0.15 percentage points (95% confidence interval [CI], -3.60 to 3.30; P = 0.90). New renal-replacement therapy was initiated in 306 of 2403 patients (12.7%) in the BMES group and in 310 of 2394 patients (12.9%) in the saline group, for a difference of -0.20 percentage points (95% CI, -2.96 to 2.56). The mean (±SD) maximum increase in serum creatinine level was 0.41±1.06 mg per deciliter (36.6±94.0 µmol per liter) in the BMES group and 0.41±1.02 mg per deciliter (36.1±90.0 µmol per liter) in the saline group, for a difference of 0.01 mg per deciliter (95% CI, -0.05 to 0.06) (0.5 µmol per liter [95% CI, -4.7 to 5.7]). The number of adverse and serious adverse events did not differ meaningfully between the groups. CONCLUSIONS: We found no evidence that the risk of death or acute kidney injury among critically ill adults in the ICU was lower with the use of BMES than with saline. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; PLUS ClinicalTrials.gov number, NCT02721654.).

Safety of ventricular arrhythmia radiofrequency ablation with half-normal saline irrigation.

AIMS: Failure of radiofrequency (RF) ablation of ventricular arrhythmias is often due to inadequate lesion size. Irrigated RF ablation with half-normal saline (HNS) has the potential to increase lesion size and reduce sodium delivery to the patient if the same volume of RF irrigant were used for normal saline (NS) and HNS but could increase risks related to steam pops and lesion size. This study aims to assess periprocedural complications and acute ablation outcome of ventricular arrhythmias ablation with HNS. METHODS AND RESULTS: Prospective assessment of outcomes was performed in 1024 endocardial and/or epicardial RF ablation procedures in 935 consecutive patients (median age 64 years, 71.2% men, 73.4% cardiomyopathy, 47.2% sustained ventricular tachycardia). Half-normal saline was selected at the discretion of the treating physician. Radiofrequency ablation power was generally titrated to a ≤15â€…Ω impedance fall with intracardiac echocardiography monitoring. Half-normal saline was used in 900 (87.9%) and NS in 124 (12.1%) procedures. Any adverse event within 30 days occurred in 13.0% of patients treated with HNS RF ablation including 4 (0.4%) strokes/transient ischaemic attacks and 34 (3.8%) pericardial effusions requiring treatment (mostly related to epicardial access). Two steam pops with perforation required surgical repair (0.2%). Patients who received NS irrigation had less severe disease and arrhythmias. In multivariable models, adverse events and acute success of the procedure were not related to the type of irrigation. CONCLUSION: Half-normal saline irrigation RF ablation with power guided by impedance fall and intracardiac echocardiography has an acceptable rate of complications and acute ablation success while administering half of the saline load expected for NS irrigation.

Repurposing of cholesterol-lowering agents in status epilepticus: A neuroprotective effect of simvastatin.

The increase of cholesterol synthesis after a status epilepticus may lead to excitotoxic processes, neuronal loss and favor the appearance of spontaneous epileptic seizures. Lowering cholesterol content could be a neuroprotective strategy. Here, we evaluated the protective effect of simvastatin administrated daily for 14 days, after the induction of a status epilepticus by intrahippocampal injection of kainic acid in mice. The results were compared to those obtained from mice showing a kainic acid-induced status epilepticus, treated daily with a saline solution, and from mice injected with a control phosphate-buffered solution without any status epilepticus. We first assessed the antiseizure effects of simvastatin by performing video-electroencephalographic recordings during the first three hours after kainic acid injection and continuously between the fifteenth and the thirty-first days. Mice treated with simvastatin had significantly fewer generalized seizures during the first three hours without a significant effect on generalized seizures after two weeks. There was a trend for fewer hippocampal electrographic seizures after two weeks. Secondly, we evaluated the neuroprotective and anti-inflammatory effects of simvastatin by measuring the fluorescence of neuronal and astrocyte markers on the thirtieth day after status onset. We found that simvastatin reduced CA1 reactive astrocytosis, demonstrated by a significant 37% decrease in GFAP-positive cells, and that simvastatin prevented the neuronal loss in CA1, demonstrated by a significant 42% increase in the NeuN-positive cells, as compared to the findings in mice with kainic acid-induced status epilepticus treated by a saline solution. Our study confirms the interest of cholesterol-lowering agents, and in particular simvastatin, in status epilepticus and paves the way for a clinical pilot study to prevent neurological sequelae after status epilepticus. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.

Normal saline, the known but least-examined fluid therapy method for preventing heme-induced nephropathy in children with glucose 6 phosphate dehydrogenase deficiency: a randomized controlled clinical trial.

BACKGROUND: Glucose 6 phosphate dehydrogenase deficiency (G6PDd) is the most common enzyme deficiency in humans. Randomized clinical trials comparing the efficacy of different types of fluid therapy for prevention of acute kidney injury (AKI) following hemolysis in patients with G6PDd are lacking. The present study aimed to compare the efficacy of three different types of fluid administration, isotonic saline with or without acetazolamide versus bicarbonate solution in prevention of AKI among children with acute hemolysis due to G6PDd. METHODS: In this double-blind randomized controlled clinical trial, 120 infants and children with acute hemolysis due to G6PDd were randomly divided into three groups consisting of 40 participants in each group. Group A received normal saline. Group B received normal saline plus oral acetazolamide at a dose of 5 mg/kg/day, and group C received half saline plus 75 mEq/L sodium bicarbonate. The primary outcome of this study was the frequency of AKI among the different types of fluid administration. RESULTS: In this study, 72 (60%) patients were boys with the mean age and length of hospital stay of 3.9 ± 2.2 years and 54.4 ± 29.9 h, respectively. AKI as the primary outcome of this study occurred only in one patient in group C and the rate of AKI did not differ significantly among patients receiving different types of fluid resuscitation (P > 0.05). CONCLUSION: Normal saline was equivalent to fluids containing alkalinizing agents in preventing heme-induced nephropathy in patients with G6PDd. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hangeshashinto for prevention of oral mucositis in patients undergoing hematopoietic stem cell transplantation: a randomized phase II study.

PURPOSE: Oral mucositis (OM) is a side effect associated with cancer treatment. Hangeshashinto (HST), a Kampo medicine, was originally prescribed to treat diarrhea, gastritis, and stomatitis. Several reports have described the effects of HST for OM induced by chemotherapy in patients with gastric or colorectal cancer. In this study, the effects of HST for prevention of OM were investigated in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Thirty patients scheduled to receive allogeneic grafts were enrolled from July 2020 to December 2021. They were randomly assigned to two groups and instructed to wash their mouth using HST dissolved in saline solution or using only saline solution three times a day. The observation period was from the initiation date of the conditioning regimen to the date of engraftment, and the end point was the incidence of OM. RESULTS: Eighteen patients developed OM, the most severe of which was Grade (G)3. There was no significant difference in the incidence of OM between the HST group and the control group. However, a negative correlation tended to be observed between the duration using HST use and the duration of OM (G2-3: P = 0.027, G3: P = 0.047). CONCLUSIONS: The present study demonstrated that HST use did not clearly inhibit onset of OM but showed a tendency to inhibit OM exacerbation. However, further studies are necessary to fully understand the effects of HST on OM in patients undergoing HSCT. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials on 7 May 2020 (jRCTs071200012).

Safety of peripherally administered 3% hypertonic saline.

BACKGROUND: Administration of 3% sodium chloride through a peripheral venous catheter is associated with risk of infusion-related adverse events (IRAE) due to its high osmolarity. Given this concern and the paucity of data regarding these events, many hospitals have policies that require central line administration of 3% sodium chloride. OBJECTIVE: The objective of this analysis was to evaluate the incidence of IRAE associated with peripheral administration of 3% sodium chloride. METHODS: This analysis included patients who received 3% sodium chloride via a peripheral venous catheter between May 2017 and August 2019. The major endpoint of this analysis was the overall incidence of IRAE, defined as the documentation of infiltration or phlebitis. A multivariable logistic regression was performed to identify potential risk factors (e.g., age, infusion rate, infusion duration, peripheral venous catheter location, and needle gauge) for development of IRAE. RESULTS: A total of 706 administrations in 422 patients were included. Seventy-four (10.5%) administrations were associated with a documented event. Based on the Infusion Nurses grading scale for infiltration or phlebitis, 48% of the events in this analysis were grade 1 in severity. Duration of infusion of 3% sodium chloride was found to be associated with an increased odds of an IRAE (OR per 1 h 1.02, 95% CI 1.01-1.02) in the multivariable analysis. Age, infusion rate, peripheral venous catheter location, and needle gauge were not independently associated with an increased risk of an IRAE. CONCLUSION: These data suggest that IRAE occurred more frequently when 3% sodium chloride was administered over a longer duration and the majority of events were mild with no permanent tissue injury. It may be reasonable to consider peripheral administration of 3% sodium chloride in the acute care setting for a short duration, although additional studies are needed to continue to evaluate its safety.

Betaine prevents cognitive dysfunction by suppressing hippocampal microglial activation in chronic social isolated male mice.

Chronic social isolation (SI) stress, which became more prevalent during the COVID-19 pandemic, contributes to abnormal behavior, including mood changes and cognitive impairment. Known as a functional nutrient, betaine has potent antioxidant and anti-inflammatory properties in vivo. However, whether betaine can alleviate the abnormal behavior induced by chronic SI in mice remains unknown. In this study, we investigated the efficacy of betaine in the treatment of behavioral changes and its underlying mechanism. Three-week-old male mice were randomly housed for 8 weeks in either group housing (GH) or SI. The animals were divided into normal saline-treated GH, normal saline-treated SI, and betaine-treated SI groups in the sixth week. The cognitive and depression-like behavior was determined in the eighth week. We found that long-term betaine administration improved cognitive behavior in SI mice but failed to prevent depression-like behavior. Moreover, long-term betaine administration inhibited hippocampal microglia over-activation and polarized microglia toward the M2 phenotype, which effectively inhibited the expression of inflammatory factors in SI mice. Finally, the protective effect of betaine treatment in SI mice might not be due to altered activity of the hypothalamic-pituitary-adrenal axis. Collectively, our findings reveal that betaine can improve SI-induced cognitive impairment, thus providing an alternative natural source for the prevention of memory loss caused by SI or loneliness.

The anti-inflammatory effects of minocycline on lipopolysaccharide-induced paw oedema in rats: a histopathological and molecular study.

Minocycline is a semi-synthetic antimicrobial agent with claimed anti-inflammatory properties reported from different experimental models. This study was aimed to evaluate the anti-inflammatory effects of minocycline, compared to the actions of two common anti-inflammatory agents, on lipopolysaccharide (LPS)-induced paw oedema through some clinical, histopathological, haematological and molecular analyses. Forty-eight rats were divided into eight groups (n = 6). In control group (Ctrl), each animal was injected with normal saline into its sub-plantar region of hind paw. In groups 2-7, hind paw oedema was induced by injection of LPS. One hour before injections, groups 1 (Ctrl) and 2 (LPS) were treated orally with distilled water, 3 and 4 with methylprednisolone (Pred) and meloxicam (Melo) and 5-7 with minocycline in doses of 50, 150 and 450 mg/kg (M50, M150 and M450, respectively). The 8th group (MC) was given minocycline (150 mg/kg) orally and normal saline was injected into sub-plantar region. Paw swelling and body temperature were assessed at 0, 2, 4, 6 and 24 h post-injections. At 24 h, samples of blood and liver, kidney, spleen and hind paw tissues were taken for haematological and histopathological examinations. Some samples of the paw were also obtained for molecular analysis of some inflammatory-related cytokines at mRNA level. Paw swelling and body temperature increased in all LPS-injected groups 2 h post-injection. In LPS group, they remained significantly increased up to 24 h; however, these parameters decreased to normal in Pred, Melo and all minocycline groups. The histological findings showed mild-to-moderate signs of inflammation in tissue samples of groups 2-6, but not in group M450. Additionally, gene expression of pro-inflammatory cytokines (IL-1ß and IL-6) increased significantly in LPS group compared to other groups. In conclusion, this study supports the role of minocycline as an anti-inflammatory agent with effects comparable to those of meloxicam and methylprednisolone.

[Efficacy of arteriovenous argatroban versus heparin flush anticoagulation after cardiovascular surgery].

Objective: To compare the effects of arteriovenous argatroban and heparin flushes on platelet count and assess the occurrence of heparin-induced thrombocytopenia (HIT) and other complications in patients undergoing cardiovascular surgeries. Methods: A single-center, prospective randomized control study was conducted. Patients who underwent cardiovascular surgery at Fuwai Hospital, Chinese Academy of Medical Sciences from March to December 2019 were randomly divided into the argatroban group (250 ml normal saline plus 2.5 mg of argatroban) and the heparin group (250 ml normal saline plus 10 mg of heparin). Platelet count, hemorrhage, and thrombosis were assessed. The 4T scores of HIT, the incidences of HIT and other complications were also evaluated. Results: A total of 491 patients (307 males and 184 females) were included in the study, with a mean age of (52.3±13.7) years. There were 245 cases in the argatroban group and 246 cases in the heparin group, respectively. There was no statistically significant difference in the preoperative platelet count between the argatroban and heparin groups [198.0 (161.0, 248.0)×109/L vs 194.0 (157.2, 243.8)×109/L, P=0.498]. Likewise, there were no statistically significant differences in the platelet count between the argatroban and heparin groups at 12 h, 1 day, and 5 days after operation [127.0 (100.0, 154.0)×109/L vs 121.5 (90.2, 149.0)×109/L, 126.0 (97.0, 162.0)×109/L vs 123.5 (88.0, 151.0)×109/L, 168.0 (130.0, 215.0) ×109/L vs 161.0 (101.0, 210.5)×109/L] (repeated measures ANOVA between groups: F=3.327, P=0.069; time comparison: F=532.523, P<0.001; time interaction between groups: F=0.675, P=0.512). The proportion of 4T scores of medium and high scores (≥4)[9.8% (24/245) vs 10.6% (26/246), P=0.777] and incidence of HIT antibody positive [1.63% (4/245) vs 1.63% (4/246), P=0.726] were similar between argatroban group and the heparin group. Mechanical ventilation time was shorter in the argatroban group than that in the heparin group [13.0 (11.0, 21.0) vs 15.5 (12.0, 21.0) h, P=0.020]. Conclusion: Compared with heparin, routine management with argatroban for arteriovenous flush in patients undergoing cardiovascular surgery does not affect the HIT incidence.

Hepatoprotective Effect of Moringa Oil on Rats under Fungicide Toxicity.

The present study is designed to evaluate whether pretreatment with moringa would have a protective effect on thioacetamide (TAA)-induced liver fibrosis, assessing biochemical and histopathological changes in Wistar male rats. Exposure to TAA induced notable biochemical and histopathological alterations. Liver fibrosis induced by TAA, along with associated biochemical and histological damage, has not been previously investigated in male rats supplemented with moringa oil. The experiment involved forty male rats distributed across four groups, each comprising ten rats. Group 1 served as controls and received intraperitoneal injections of saline solution twice weekly for six weeks. Group 2 rats were injected with 300 mg/kg body weight of TAA (Sigma-Aldrich Corp.) twice weekly for the same duration. Group 3 rats were orally supplemented with moringa oil at 800 mg/kg body weight/day and received intraperitoneal injections of TAA at the same dosage as Group 2 for six weeks. Finally, Group 4 rats were injected with saline solution twice weekly and orally supplemented with moringa oil at 800 mg/kg body weight/day for the same period. At the end of the experiment, we determined body weight and performed liver function analysis. Additionally, we examined the liver histology of the different groups. Results showed that moringa oil treatment protected rat livers from TAA toxicity by improving liver function analysis and preventing liver fibrosis. Moringa oil can be considered a promising agent for protection against TAA toxicity.

Balanced Crystalloid Versus Normal Saline as Resuscitative Fluid in Diabetic Ketoacidosis.

BACKGROUND: Large volume resuscitation with normal saline (NS) may be associated with iatrogenic hyperchloremia and renal injury. OBJECTIVE: The purpose of this study was to assess clinical outcomes associated with the use of Lactated Ringer's (LR) compared to NS as resuscitative fluid in diabetic ketoacidosis (DKA). METHODS: Single-center, retrospective analysis of patients admitted for DKA. The primary objective of this study was to evaluate the incidence of iatrogenic hyperchloremia associated with fluid resuscitation using balanced crystalloid compared to NS. RESULTS: Iatrogenic hyperchloremia occurred more frequently in the NS group compared to the LR group (74.4% vs 64.2%; P = 0.05). Mean maximum serum chloride was higher in the NS group (115.7 mmol/L vs 113.7 mmol/L; P = 0.004). Incidence of hypernatremia was higher in the NS group (18.3% vs 9.3%; P = 0.02). There was no significant difference in the incidence of AKI; however, mean change in serum creatinine at 48 hours showed a significantly greater decrease in the LR group (-0.15 mg/dL vs -0.04 mg/dL; P = 0.002). No significant differences were found in intensive care unit (ICU) length of stay or total hospital length of stay. CONCLUSION AND RELEVANCE: This study found a statistically significant reduction in the incidence of iatrogenic hyperchloremia with the use of LR compared to NS as fluid resuscitation in DKA. Serum creatinine was more improved in the LR group versus NS group at 48 hours. Preferential use of balanced crystalloid for fluid resuscitation in DKA may reduce incidence of hyperchloremia and support renal recovery in this population.

Use of normal saline and incidence of dyselectrolytaemia in children following kidney transplantation.

BACKGROUND: The use of hypotonic fluid, such as 0.45% saline, following kidney transplantation (KT) in children is associated with a high incidence of electrolyte imbalance, especially hyponatraemia. This can result in serious adverse events, such as cerebral oedema and seizures. The aim of this study was to investigate the incidence of electrolyte disturbance in children when 0.9% saline was the intravenous fluid used in the first 72 h following KT. METHODS: This is a retrospective, observational study of 50 consecutive KT undertaken between January 2017 and January 2019 at a single centre. RESULTS: The median age at KT was 9.2 years (IQR 4-14) and 16 (32%) were females. Thirty-two (64%) were living related donor (LRD) KT and 22 (44%) were carried out in children < 20 kg. The mean volume of fluid administered intra-operatively, and on Day 1, Day 2 and Day 3, were 73 ml/kg, 124 ml/kg, 97 ml/kg and 86 ml/kg, respectively. Hyponatraemia was noted in 4%, hypernatraemia in 18%, hyperkalaemia in 18%, hyperchloraemia in 68% and low bicarbonate was seen in 88%. Fifteen percent of the children had an episode of hyperglycaemia. None of the children developed symptomatic dyselectrolytaemia. There was delayed graft function (DGF) in 4 (8%) recipients - all deceased donor (DD) KT, including 2 who received donations after circulatory death. CONCLUSIONS: While the use of 0.9% saline is associated with a high incidence of electrolyte disturbances, including hyperkalaemia, it reduces the risk of hyponatraemia. None of the children developed a symptomatic electrolyte abnormality. A higher resolution version of the Graphical abstract is available as Supplementary information.

Heparin versus 0.9% sodium chloride locking for prevention of occlusion in central venous catheters in adults.

BACKGROUND: Intermittent locking of central venous catheters (CVCs) is undertaken to help maintain their patency and performance. There are systematic variations in care: some practitioners use heparin (at different concentrations), whilst others use 0.9% sodium chloride (normal saline). This review looks at the effectiveness and safety of intermittent locking with heparin compared to normal saline, to see if the evidence establishes whether one is better than the other. This is an update of an earlier Cochrane Review. OBJECTIVES: To evaluate the benefits and harms of intermittent locking of CVCs with heparin versus normal saline in adults to prevent occlusion. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 20 October 2021. SELECTION CRITERIA: We included randomised controlled trials in adults ≥ 18 years of age with a CVC that compared intermittent locking with heparin at any concentration versus normal saline. We excluded studies on infants and children from this review. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were occlusion of CVCs and duration of catheter patency. Our secondary outcomes were CVC-related bloodstream infections and CVC-related colonisation, mortality, haemorrhage, heparin-induced thrombocytopaenia, CVC-related thrombosis, number of additional CVC insertions, abnormality of coagulation profile and allergic reactions to heparin. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified one new RCT with 30 participants for this update. We included a total of 12 RCTs with 2422 participants. Data for meta-analysis were available from all RCTs. We noted differences in methods used by the included studies and variation in heparin concentrations (10 to 5000 IU/mL), time to follow-up (1 to 251.8 days), and the unit of analysis used (participant, catheter, line access). Five studies included ICU (intensive care unit) patients, two studies included oncology patients, and the remaining studies included miscellaneous patients (chronic kidney disease, haemodialysis, home care patients, etc.). Primary outcomes Overall, combined results may show fewer occlusions with heparin compared to normal saline but this is uncertain (risk ratio (RR) 0.70, 95% confidence interval (CI) 0.51 to 0.95; 10 studies; 1672 participants; low-certainty evidence). We pooled studies that used participant or catheter as the unit of analysis. We carried out subgroup analysis by unit of analysis. No clear differences were detected after testing for subgroup differences (P = 0.23). We found no clear evidence of a difference in the duration of catheter patency with heparin compared to normal saline (mean difference (MD) 0.44 days, 95% CI -0.10 to 0.99; 6 studies; 1788 participants; low-certainty evidence). Secondary outcomes We found no clear evidence of a difference in the following outcomes: CVC-related bloodstream infections (RR 0.66, 95% CI 0.08 to 5.80; 3 studies; 1127 participants; very low-certainty evidence); mortality (RR 0.76, 95% CI 0.44 to 1.31; 3 studies; 1100 participants; very low-certainty evidence); haemorrhage (RR 1.54, 95% CI 0.41 to 5.74; 3 studies; 1197 participants; very low-certainty evidence); or heparin-induced thrombocytopaenia (RR 0.21, 95% CI 0.01 to 4.27; 3 studies; 443 participants; very low-certainty evidence). The main reasons for downgrading the certainty of evidence for the primary and secondary outcomes were unclear allocation concealment, suspicion of publication bias, imprecision and inconsistency. AUTHORS' CONCLUSIONS: Given the low-certainty evidence, we are uncertain whether intermittent locking with heparin results in fewer central venous catheter occlusions than intermittent locking with normal saline in adults. Low-certainty evidence suggests that heparin may have little or no effect on catheter patency duration. Although we found no evidence of differences in safety (CVC-related bloodstream infections, mortality, or haemorrhage), the combined studies were not powered to detect rare adverse events such as heparin-induced thrombocytopaenia. Further research conducted over longer periods would reduce the current uncertainties.

Perioperative Normal Saline Administration and Delayed Graft Function in Patients Undergoing Kidney Transplantation: A Retrospective Cohort Study.

BACKGROUND: Perioperative normal saline administration remains common practice during kidney transplantation. The authors hypothesized that the proportion of balanced crystalloids versus normal saline administered during the perioperative period would be associated with the likelihood of delayed graft function. METHODS: The authors linked outcome data from a national transplant registry with institutional anesthesia records from 2005 to 2015. The cohort included adult living and deceased donor transplants, and recipients with or without need for dialysis before transplant. The primary exposure was the percent normal saline of the total amount of crystalloids administered perioperatively, categorized into a low (less than or equal to 30%), intermediate (greater than 30% but less than 80%), and high normal saline group (greater than or equal to 80%). The primary outcome was the incidence of delayed graft function, defined as the need for dialysis within 1 week of transplant. The authors adjusted for the following potential confounders and covariates: transplant year, total crystalloid volume, surgical duration, vasopressor infusions, and erythrocyte transfusions; recipient sex, age, body mass index, race, number of human leukocyte antigen mismatches, and dialysis vintage; and donor type, age, and sex. RESULTS: The authors analyzed 2,515 records. The incidence of delayed graft function in the low, intermediate, and high normal saline group was 15.8% (61/385), 17.5% (113/646), and 21% (311/1,484), respectively. The adjusted odds ratio (95% CI) for delayed graft function was 1.24 (0.85 to 1.81) for the intermediate and 1.55 (1.09 to 2.19) for the high normal saline group compared with the low normal saline group. For deceased donor transplants, delayed graft function in the low, intermediate, and high normal saline group was 24% (54/225 [reference]), 28.6% (99/346; adjusted odds ratio, 1.28 [0.85 to 1.93]), and 30.8% (277/901; adjusted odds ratio, 1.52 [1.05 to 2.21]); and for living donor transplants, 4.4% (7/160 [reference]), 4.7% (14/300; adjusted odds ratio, 1.15 [0.42 to 3.10]), and 5.8% (34/583; adjusted odds ratio, 1.66 [0.65 to 4.25]), respectively. CONCLUSIONS: High percent normal saline administration is associated with delayed graft function in kidney transplant recipients.

Association study of fasting blood glucose and salt sensitivity of blood pressure in community population: The EpiSS study.

BACKGROUND AND AIMS: To evaluate the association between fasting blood glucose (FBG) and salt sensitivity of blood pressure (SSBP). METHODS AND RESULTS: This study is based on the baseline survey of systemic epidemiology of salt sensitivity study. Subjects were classified into salt sensitive (SS) and salt resistant groups according to blood pressure (BP) changes during the modified Sullivan's acute oral saline load and diuresis shrinkage test. Multivariate logistic and linear regression were used to evaluate associations between FBG with SS or BP changes. A total of 2051 participants were included in the analyses with 581 (28.33%) for SS. Multiple analysis showed that for every interquartile range increase in FBG, the OR (95%CI) for SS was 1.140 (1.069, 1.215), ß (95%CI) for mean arterial pressure change (ΔMAP1), systolic and diastolic BP changes during saline load were 0.421 (0.221, 0.622), 0.589 (0.263, 0.914) and 0.340 (0.149, 0.531), respectively. Compared to the lowest FBG quartile (Q1), the OR (95%CI) for SS in Q3 and Q4 were 1.342 (1.014, 1.776) and 1.577 (1.194, 2.084), respectively. Compared to subjects with normal FBG, the ß (95%CI) for ΔMAP1 was 0.973 (0.055, 1.891) in subjects with impaired FBG, and was 1.449 (0.602, 2.296) in patients with diabetes mellitus. Stratified analyses showed significant and stronger associations between FBG with SSBP in youngers, females, hypertensives, non-diabetics, non-current smokers and non-current drinkers. CONCLUSION: Our findings suggest FBG is an independent, dose-dependent associated factor for SSBP, and prevention of SS focusing on controlling FBG elevation in the early stage is important.

Effect of Hydraulic Expansion on Arteriovenous Fistula of Hemodialysis Patients.

BACKGROUND: Chronic kidney disease has become a serious public health problem in China. Our study is to explore effect of hydraulic expansion on arteriovenous fistula (AVF) of hemodialysis patients. METHODS: A total of 190 patients with end-stage renal disease (ESRD) were randomly divided into hydraulic expansion group (n = 117) and conventional surgery group (n = 73). Age, sex, the cause of ESRD, height, weight, body mass index (BMI), blood pressure, and diameter of artery and vein from ultrasonography before surgery from patients were recorded. Doppler ultrasonography of vessel was performed with a 12-MHz scanning probe for vascular measurements. The time of first cannulation was recorded. Primary and secondary patency rates were compared between the two groups. RESULTS: The mean arterial pressure for this cohort of patients was around 98.12 mm Hg. The mean diameters of artery and vein ready for anastomoses measured by ultrasonography before surgery were 1.96 and 2.04 mm, respectively. Age, weight, BMI, sex ratio, the cause of renal failure, history of catheter insertion, mean arterial pressure, frequency of hemodialysis, blood flow of hemodialysis, and the mode of anastomoses of AVF in conventional surgery group were similar to hydraulic expansion group. There were no differences in stroke volume of radius arterial and venous pressure before dilation between the two groups. The stroke volume of radius artery increased significantly after hydraulic expansion than before dilation and control group. The primary patency rates of AVF in patients with hydraulic expansion were higher significantly than conventional surgery group. The secondary patency rates in conventional surgery group were not different from hydraulic expansion group. CONCLUSION: Hydraulic expansion showed no difference from conventional surgery in complication after operation, and could decrease the time reliance on catheters and the risk of catheter-related infection, thrombosis, and decrease the related medical care costs.

Bolus intravenous 0.9% saline leads to interstitial permeability pulmonary edema in healthy volunteers.

PURPOSE: Bolus intravenous administration of 0.9% saline has been associated with the development of pulmonary edema, and increased mortality. An animal model has previously demonstrated that rapid intravenous administration of 0.9% saline was associated with non-hydrostatic lung injury with increased lung lavage protein. We hypothesized that this non-hydrostatic effect would also occur in human volunteers. METHODS: In a randomized, cross-over study of 14 healthy male subjects, the lung lavage protein concentration and cardiorespiratory effects of an intervention with rapid intravenous administration of 30 mL/kg of 0.9% saline were compared with sham intervention. Bronchoalveolar lavage (BAL) was performed after fluid administration. Doppler echocardiography, lung ultrasound, pulmonary function tests, and blood sampling were performed before and after each intervention. RESULTS: The BAL total protein concentration was greater after 0.9% saline administration than with sham (196.1 µg/mL (SD 87.6) versus 129.8 µg/mL (SD 55.4), respectively (p = 0.020). Plasma angiopoietin-2 concentration was also increased to 2.26 ng/mL (SD 0.87) after 0.9% saline administration compared with sham 1.53 ng/mL (SD 0.69) (p < 0.001). There were small increases in stroke volume (from 58 mL (IQR 51-74) to 66 mL (IQR 58-74), p = 0.045) and Doppler echocardiography left ventricle E/e' ratio (from 5.0 (IQR 4.5-6.0) to 5.7 (IQR 5.3-6.3), p = 0.007), but no changes to right ventricular function. CONCLUSION: Rapid intravenous administration of 0.9% saline leads to interstitial permeability pulmonary edema in healthy human volunteers. Further research is now warranted to understand these effects in critically ill patients.

Renal insufficiency following contrast media administration trial III: Urine flow rate-guided versus left-ventricular end-diastolic pressure-guided hydration in high-risk patients for contrast-induced acute kidney injury. Rationale and design.

BACKGROUND: Urine flow rate (UFR)-guided and left-ventricular end-diastolic pressure (LVEDP)-guided hydration regimens have been proposed to prevent contrast-induced acute kidney injury (CIAKI). The REnal Insufficiency Following Contrast MEDIA Administration triaL III (REMEDIAL III) is a randomized, multicenter, investigator-sponsored trial aiming to compare these two hydration strategies. METHODS: Patients at high risk for CIAKI (that is, those with estimated glomerular filtration rate ≤ 45 mL/min/1.73 m2 and/or with Mehran's score ≥11 and/or Gurm's score >7) will be enrolled. Patients will be randomly assigned to (a) LVEDP-guided hydration with normal saline (LVEDP-guided group) and (b) UFR-guided hydration carried out by the RenalGuard system (RenalGuard group). Seven-hundred patients (350 in each arm) will be enrolled. In the LVEDP-guided group the fluid infusion rate will be adjusted according to the LVEDP as follows: 5 mL kg-1 hr-1 for LVEDP ≤12 mmHg, 3 mL kg-1 hr-1 for LVEDP 13-18 mmHg, and 1.5 mL kg-1 hr-1 for LVEDP >18 mmHg. In the RenalGuard group hydration with normal saline plus low-dose of furosemide is controlled by the RenalGuard system, in order to reach and maintain a high (>300 mL/hr) UFR. In all cases, iobitridol (a low-osmolar, nonionic contrast agent) will be administered. RESULTS: The primary endpoint is the composite of CIAKI (i.e., serum creatinine increase ≥25% and/or ≥0.5 mg/dL from the baseline to 48 hr after contrast media exposure) and/or acute pulmonary edema. CONCLUSION: The REMEDIAL III will test the hypothesis that the UFR-guided hydration is superior to the LVEDP-guided hydration to prevent the composite of CIAKI and/or acute pulmonary edema.

Saline versus Lactated Ringer's Solution: The Saline or Lactated Ringer's (SOLAR) Trial.

BACKGROUND: Both saline and lactated Ringer's solutions are commonly given to surgical patients. However, hyperchloremic acidosis consequent to saline administration may provoke complications. The authors therefore tested the primary hypothesis that a composite of in-hospital mortality and major postoperative complications is less common in patients given lactated Ringer's solution than normal saline. METHODS: The authors conducted an alternating cohort controlled trial in which adults having colorectal and orthopedic surgery were given either lactated Ringer's solution or normal saline in 2-week blocks between September 2015 and August 2018. The primary outcome was a composite of in-hospital mortality and major postoperative renal, respiratory, infectious, and hemorrhagic complications. The secondary outcome was postoperative acute kidney injury. RESULTS: Among 8,616 qualifying patients, 4,187 (49%) were assigned to lactated Ringer's solution, and 4,429 (51%) were assigned to saline. Each group received a median 1.9 l of fluid. The primary composite of major complications was observed in 5.8% of lactated Ringer's versus 6.1% of normal saline patients, with estimated average relative risk across the components of the composite of 1.16 (95% CI, 0.89 to 1.52; P = 0.261). The secondary outcome, postoperative acute kidney injury, Acute Kidney Injury Network stage I-III versus 0, occurred in 6.6% of lactated Ringer's patients versus 6.2% of normal saline patients, with an estimated relative risk of 1.18 (99.3% CI, 0.99 to 1.41; P = 0.009, significance criterion of 0.007). Absolute differences between the treatment groups for each outcome were less than 0.5%, an amount that is not clinically meaningful. CONCLUSIONS: In elective orthopedic and colorectal surgery patients, there was no clinically meaningful difference in postoperative complications with lactated Ringer's or saline volume replacement. Clinicians can reasonably use either solution intraoperatively.

Routine Stent Flushing with Heparinized Saline during Distal Filter-Protected Carotid Artery Stenting: A Technical Modification to Reduce Delayed Embolization.

INTRODUCTION: Delayed embolization after filter-protected carotid artery stenting (CAS) may occur because of the protrusion and release of loose atherosclerotic plaque fragments through the stent cells. METHODS AND RESULTS: We describe a technical modification to the standard filter-protected CAS by introducing an extra step, that of washing away the luminal stent surface debris with heparinized saline while the filter is still in place. Aided by the guiding catheter, flushing heparinized saline under manual pressure against the stent will force all loose fragments distally in the internal carotid artery to be captured by the overlying filter. CONCLUSIONS: Stent washout with heparinized saline before filter retrieval during filter-protected CAS may potentially increase debris capture and reduce delayed embolization.