OBJECTIVE: To evaluate the risks and benefits of different resuscitation fluids in patients with early sepsis and septic shock by observing and comparing clinical indicators, clinical outcomes, and the concentration changes of glycocalyx biomarkers, and to determine how to appropriately select suitable resuscitation fluids for sepsis patients to aid fluid therapy. METHODS: A single center, prospective, randomized controlled trial was conducted. Patients with early sepsis and septic shock who have required fluid resuscitation after capacity status assessment admitted to the department of critical care medicine of Fourth Hospital of Hebei Medical University from April to October 2023 were enrolled. Patients were randomly assigned to either the experimental group (balanced crystalloid solution+albumin) or the control group (balanced crystalloid solution) by a random number table method. Clinical data of both groups of patients before and after resuscitation at 3, 8, and 24 hours were monitored, and blood samples were collected, enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of plasma glycocalyx biomarker syndecan-1. The 28-day and 90-day survival rates and complications were also assessed. RESULTS: A total of 66 patients were enrolled, including 44 in the experimental group and 22 in the control group. The baseline data of two groups were balanced and comparable. There was no statistically significant difference in the plasma concentration of syndecan-1 between the experimental group and the control group before and after resuscitation, and both showed a trend of first increasing and then decreasing. However, the plasma syndecan-1 level in the control group at 8 hours and 24 hours after resuscitation were significantly higher than the baseline level before resuscitation [ng/L: 19.02 (14.41, 27.80), 18.95 (12.40, 22.50) vs. 14.67 (11.57, 21.14), both P < 0.05], while there was no statistically significant difference at any time point within the experimental group. The correlation analysis between plasma syndecan-1 level and lactic acid, albumin, and sequential organ failure assessment (SOFA) in all patients showed that a positive correlation between syndecan-1 level and SOFA score before resuscitation (r = 0.247, P = 0.046), and a negative correlation between syndecan-1 level and albumin level at 24 hours after resuscitation (r = -0.308, P = 0.012). There were no statistically significant differences in 28-day and 90-day mortality, length of hospital stay, length of intensive care unit (ICU) stay, duration of mechanical ventilation, blood purification time, number of organ injuries, and complications between the two groups. However, the baseline albumin level in the experimental group was significantly lower than that in the control group (g/L: 28.7±4.5 vs. 31.6±4.2, P < 0.05). Analysis of clinical treatment data showed that compared with the control group, the experimental group had lower absolute lactate level at 8 hours and 24 hours after resuscitation [mmol/L: 8 hours was 1.30 (1.00, 1.88) vs. 1.60 (1.30, 3.05), 24 hours was 1.15 (0.80, 1.78) vs. 1.55 (1.08, 2.05), both P < 0.05], and higher lactate clearance rate [8 hours was 45% (27%, 56%) vs. 20% (-4%, 46%), 24 hours was 55% (34%, 70%) vs. 34% (-14%, 59%), both P < 0.05]. However, there were no statistically significant differences in the amount of fluid resuscitation, use of vasoactive drugs, and oxygenation index between the two groups during the resuscitation process. Multivariate Logistic regression analysis showed that body mass index (BMI) was independently correlated with 90-day mortality [odds ratio (OR) = 1.991, 95% confidence interval (95%CI) was 1.023-3.387, P = 0.043]. CONCLUSIONS There are no significant difference in plasma syndecan-1 level during fluid resuscitation of early sepsis and septic shock patients using balanced crystalloid fluid and balanced crystalloid fluid combined with albumin resuscitation, and there are no statistically significant differences in the impact on 28-day and 90-day prognosis, length of hospital stay, complications, and other aspects of the patients. However, compared to balanced crystalloid fluid, the combination of balanced crystalloid fluid and albumin for fluid resuscitation in sepsis patients has lower lactate level and better lactate clearance effect, but further validation is still needed through large-scale randomized controlled trials.
Humans ; Clinical Relevance ; Crystalloid Solutions/administration & dosage* ; Fluid Therapy/methods* ; Glycocalyx/metabolism* ; Isotonic Solutions/administration & dosage* ; Prospective Studies ; Resuscitation/methods* ; Sepsis/therapy* ; Shock, Septic/therapy* ; Syndecan-1/blood*

Fluid resuscitation is an essential intervention in critically ill patients, and its ultimate goal is to restore tissue perfusion. Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions, hypoperfusion, shock, and so forth, leading to disturbed microcirculatory perfusion and organ dysfunction. Therefore, maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy. Like drugs, however, different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx. The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx. Many animal studies have shown that normal saline might be associated with glycocalyx degradation, but clinical studies have not confirmed this finding. Hydroxyethyl starch (HES), rather than other synthetic colloids, may restore the glycocalyx. However, the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies. Some studies have suggested that albumin may restore the glycocalyx, whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation. Notably, most studies did not correct the effects of the infusion rate or fluid volume; therefore, the results of using balanced crystalloids remain unclear. Moreover, mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity, and this still requires confirmation by high-quality clinical studies.
Animals ; Colloids ; Crystalloid Solutions/therapeutic use* ; Fluid Therapy ; Glycocalyx ; Humans ; Hydroxyethyl Starch Derivatives ; Isotonic Solutions ; Microcirculation ; Resuscitation

Fluid resuscitation, hemostasis, and transfusion is essential in care of hemorrhagic shock. Although estimation of the residual blood volume is crucial, the standard measuring methods are impractical or unsafe. Vital signs, central venous or pulmonary artery pressures are inaccurate. We hypothesized that the residual blood volume for acute, non-ongoing hemorrhage was calculable using serial hematocrit measurements and the volume of isotonic solution infused. Blood volume is the sum of volumes of red blood cells and plasma. For acute, non-ongoing hemorrhage, red blood cell volume would not change. A certain portion of the isotonic fluid would increase plasma volume. Mathematically, we suggest that the residual blood volume after acute, non-ongoing hemorrhage might be calculated as 0·25N/[(Hct1/Hct2)-1], where Hct1 and Hct2 are the initial and subsequent hematocrits, respectively, and N is the volume of isotonic solution infused. In vivo validation and modification is needed before clinical application of this model.
Blood Volume ; Hematocrit ; Humans ; Isotonic Solutions/*therapeutic use ; *Models, Theoretical ; Shock, Hemorrhagic/*prevention & control/*therapy

OBJECTIVETo explore the regulative effects and possible mechanisms of emodin on autophagy induced by starvation in rat's renal tubular epithelial cells (NRK-52E).

METHODFirstly, Hank's balanced salt solution (HBSS) was used to induce starvation and the protein expression of microtubule-associated protein 1 light chain 3 (LC3) I/II, an autophagic marker of mammalian congener, was detected by Western blot with or without the treatment of emodin. Secondly, the changes of red fluorescent protein-microtubule associated protein light chain3 (RFP-LC3) fluorescent particles, treated by HBSS (1 mL) and bafilomycin A1 (10 nmol x L(-1)) with or without emodin, were observed through fluorescence microscopy in NRK-52E cells transient transfected by RFP-LC3 plasmid. With the intervention of mammalian target of rapamycin mTOR inhibitor rapamycin (100 nmol x L(-1)) , the effect of blocking mTOR signaling pathway on autophagic inhibition of emodin was observed. Finally, the effect of mTOR signaling pathway on autophagic inhibition of emodin was further evaluated through the over-expression of endogenous mTOR inhibitory protein DEP domain-containing mTOR-interacting protein-(DEPTOR).

RESULTHBSS hunger could induce high protein expression of LC3 II in NRK-52E cells, and the intervention of emodin could reverse the unregulated protein expression of LC3 II induced by HBSS. The number of RFP-LC3 fluorescent particles was increased after the co-treatment of HBSS and bafilomycin A1, and this increase was inhibited by emodin. After the co-treatment of rapamycin, emodin and HBSS, the LC3 II protein expression restored in NRK-52E cells, compared with the treatment of HBSS. Over-expression of DEPTOR could also block the inhibitive effect of emodin on LC3 II protein expression.

CONCLUSIONEmodin could inhibit HBSS-induced LC3 II protein expression and the activation of autophagy in NRK-52E cells, and the effect of blocking autophagy may be mediated through mTOR signaling pathway.

Animals ; Autophagy ; drug effects ; Cell Line ; Down-Regulation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Emodin ; pharmacology ; Isotonic Solutions ; adverse effects ; Kidney Tubules ; cytology ; drug effects ; metabolism ; Microtubule-Associated Proteins ; genetics ; metabolism ; Rats ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism

Parkland formula is the most widely used resuscitation formula in burn care. However, a growing number of disputes have been raised along with the development of medical technology, among which its total volume and composition of the fluid are the two foci. Firstly, Parkland formula may lead to an untoward phenomenon nicknamed "fluid creep", which may lead to complications such as abdominal compartment syndrome. Secondly, along with the deeper understanding of how permeability of blood vessels changes after burn injury, colloid is recommended to be given after the third 8 h post-burn. Additionally, controversy exists in the choice of different colloid solutions. The safety of different colloid solutions remains to be further elucidated. This article will deal with all of the above-mentioned problems.
Burns ; physiopathology ; therapy ; Fluid Therapy ; methods ; Humans ; Isotonic Solutions ; therapeutic use ; Resuscitation ; methods ; Treatment Outcome

BACKGROUNDHypotension induced by combined spinal epidural anesthesia in parturient with hypertensive disorders of pregnancy (HDP) can easily compromise blood supply to vital organs including uteroplacental perfusion and result in fetal distress. The aim of this study was to investigate whether the goal-directed fluid therapy (GDFT) with LiDCO rapid system can improve well-being of both HDP parturient and their babies.

METHODSFifty-two stable HDP parturient scheduled for elective cesarean delivery were recruited. After loading with 10 ml/kg lactated Ringer's solution (LR), parturient were randomized to the GDFT and control group. In the GDFT group, individualized fluid therapy was guided by increase in stroke volume (ΔSV) provided via LiDCO rapid system. The control group received the routine fluid therapy. The primary endpoints included maternal hypotension and the doses of vasopressors administered prior to fetal delivery. The secondary endpoints included umbilical blood gas abnormalities and neonatal adverse events.

RESULTSThe severity of HDP was similar between two groups. The total LR infusion (P < 0.01) and urine output (P < 0.05) were higher in the GDFT group than in the control group. Following twice fluid challenge tests, the systolic blood pressure, mean blood pressure, cardiac output and SV in the GDFT group were significantly higher, and the heart rate was lower than in the control group. The incidence of maternal hypotension and doses of phenylephrine used prior to fetal delivery were significantly higher in the control group than in the GDFT group (P < 0.01). There were no differences in the Apgar scores between two groups. In the control group, the mean values of pH in umbilical artery/vein were remarkably decreased (P < 0.05), and the incidences of neonatal hypercapnia and hypoxemia were statistically increased (P < 0.05) than in the GDFT group.

CONCLUSIONSDynamic responsiveness guided fluid therapy with the LiDCO rapid system may provide potential benefits to stable HDP parturient and their babies.

Adult ; Anesthesia, Epidural ; methods ; Anesthesia, Spinal ; methods ; Blood Pressure ; Cesarean Section ; methods ; Female ; Fluid Therapy ; methods ; Humans ; Hypertension, Pregnancy-Induced ; Infant, Newborn ; Isotonic Solutions ; Pregnancy ; Pregnancy Outcome

Hemorrhage is the second most common cause of death among trauma patients and almost half of the deaths occur within 24 hours after arrival. Damage control resuscitation is a new paradigm for patients with massive bleeding. It consists of permissive hypotension, hemostatic resuscitation and transfusion strategies, and damage control surgery. Permissive hypotension seems to have better results before the bleeding is controlled. The strategy of fluid resuscitation is minimizing crystalloid infusion and increasing early transfusion with a high ratio of fresh frozen plasma to packed red cells. Damage control surgery is done when the patient's condition is unfit for definitive surgery. Hemorrhage and contamination control with temporary abdominal closure is performed before transferring the patients to intensive care unit and the operating room for a permanent laparotomy.
Blood Transfusion ; Fluid Therapy ; methods ; Hemorrhage ; therapy ; Humans ; Isotonic Solutions

OBJECTIVETo explore the effects and molecular mechanisms of rhein on reducing starvation-induced autophagic protein expression in renal tubular epithelial ( NRK-52E) cells.

METHODHank's balanced salt solution (HBSS) was used to induce NRK-52E cells to be in the state of starvation. After the intervention of HBSS for 0, 0.5,1, 2 and 6 hours, firstly, the protein expression of microtubule-associated protein 1 light chain 3(LC3 I/II), which is a key protein in autophagy, was detected. Secondly, the protein expressions of mammalian target of rapamycin (mTOR) and phosphorylated-mTOR Ser2448 (p-mTOR S2448) were examined. And then, after the co-treatment of rhein (5 mg x L(-1)) and HBSS (1 mL) without or with mTOR inhibitor, rapamycin (100 nmol x L(-1)), the protein expressions of LC3 I/II, mTOR and p-mTOR S2448 were tested, respectively.

RESULTHBSS could induce the up-regulation of LC3 II and the down-regulation of p-mTOR S2448 at protein expression level in NRK-52E cells. The co-treatment of rhein and HBSS could reversely regulate the protein expressions of LC3 II and p-mTOR S2448 in NRK-52E cells significantly. The co-treatment of rapamycin, rhein and HBSS could recover the level of LC3 II protein expression in HBSS-intervened NRK-52E cells.

CONCLUSIONHBSS induces autophagy in renal tubular epithelial cells by inhibiting mTOR signaling pathway activation. Rhein reduces the autophagic protein expression in renal tubular epithelial cells through regulating mTOR signaling pathway activation, which is the possible effects and molecular mechanisms.

Animals ; Anthraquinones ; pharmacology ; Autophagy ; drug effects ; Cells, Cultured ; Epithelial Cells ; drug effects ; metabolism ; Isotonic Solutions ; pharmacology ; Kidney Tubules ; drug effects ; metabolism ; Microtubule-Associated Proteins ; genetics ; Rats ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; antagonists & inhibitors ; genetics ; physiology

OBJECTIVESTo compare the cardioprotection effect between blood and crystalloid cardioplegia during cardiac surgery in adult patients, and provide a theoretical basis for optimal myocardial protection strategies.

METHODSA meta-analysis of randomized controlled trials (RCT) studies about comparing blood and crystalloid cardioplegia in adult patients undergoing cardiac surgery were performed. Cochrane library (Issue 3, 2011), MEDLINE, EMBase, PubMed, HighWire, CBM and CNKI were searched from January 1985 to December 2011. Studies were assessed according to the Cochrane Handbook for systematic reviews. Data were extracted from these trials and analyzed by RevMan5.1 software.

RESULTSSixteen trials involved 3934 patients were included, 2004 cases were in blood group, and 1930 were in crystalloid group. There was no statistical heterogeneity between studies using a fixed effects model. Meta-analysis indicated that, there were no significant differences between blood and crystalloid group in the incidence of postoperative 30 days mortality (OR = 1.11, 95%CI: 0.59 - 2.08, P = 0.74), the incidence of postoperative low cardiac output (OR = 0.98, 95%CI: 0.41 - 2.33, P = 0.85), the incidence of perioperative myocardial infarctions (OR = 0.85, 95%CI: 0.55 - 1.29, P = 0.44), and inotropic support requirement (OR = 1.05, 95%CI: 0.81 - 1.38, P = 0.70).

CONCLUSIONThe blood cardioplegia is no difference with crystalloid cardioplegia in adult patients undergoing cardiac surgery.

Adult ; Cardiac Surgical Procedures ; Cardioplegic Solutions ; Humans ; Isotonic Solutions ; Postoperative Complications ; epidemiology ; Randomized Controlled Trials as Topic

BACKGROUND: Gentamicin reduces acetylcholine release and clindamycin causes end-plate ion channel blockade. Because of these reasons, two drugs show muscular relaxant effect and potentiate the action of nondepolarizing neuromuscular agents. This study was intended to evaluate the effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade and the interaction between these drugs. METHODS: Male Sprague-Dawley rats' phrenic nerves and diaphragms were installed in a bath containing Krebs solution. They were divided into three study groups. The first group was pre-treated with 0.1 (n = 3), 0.2 (n = 4) or 0.5 (n = 3) mM gentamicin and the tension was measured as the concentration of rocuronium was increased. The second group was experimented by increasing gentamicin on 0.25 (n = 5), 0.5 (n = 6) or 1.0 (n = 6) mM clindamycin. The final group was pre-treated with various combinations of gentamicin and clindamycin. The drug concentration was gradually increased until single twitch tension decreased by around 80%. Effective concentration was calculated using a probit model and interaction indices derived the Loewe additivity. RESULTS: The administration of gentamicin and the combination of gentamicin and clindamycin enhanced rocuronium-induced neuromuscular blockade. At 0.2 and 0.5 mM gentamicin, synergistic interactions with rocuronium were observed. Likewise, at 0.5 and 1.0 mM clindamycin, synergistic interactions with gentamicin appeared. When all three drugs were combined, in the tetanic fade, all the groups except for those administered with 0.01 mM gentamicin and 0.25 mM clindamycin showed synergistic interactions. CONCLUSIONS: This study demonstrate that gentamicin and clindamycin potentiated rocuronium induced neuromuscular blockade. Moreover, it was found that these drugs interacted synergistically.
Acetylcholine ; Androstanols ; Baths ; Clindamycin ; Diaphragm ; Gentamicins ; Humans ; Ion Channels ; Isotonic Solutions ; Male ; Neuromuscular Agents ; Neuromuscular Blockade ; Phrenic Nerve ; Refractory Period, Electrophysiological