Intranasal self-administration of high-pressure physiological saline isotonic solution ameliorates dry eye symptoms and tear film composition: a pilot study.

OBJECTIVE: High-pressure physiological saline isotonic solution (HPpSIS) delivery into the nasal cavity was found to modulate the local expression of immune cells, increase NGF protein, and enhance the NGF receptors' expression. Since the nasal cavity directly communicates with the eye and as NGF was previously found to ameliorate the symptoms of dry eye when topically delivered, the aim of this study was to establish whether the HPpSIS might ameliorate ocular dryness and tear film composition. SUBJECTS AND METHODS: This is an observational self-controlled case study carried out on 16 patients with dry-eye diagnosis, concerning 3-month self-administration of HPpSIS and two serial assessments of the ocular surface and tear film. OSDI questionnaire was used for ocular symptoms of dryness. BUT and Schirmer tests were used for qualitative and quantitative tear film analysis. The lipid composition was also examined. R-studio was employed for the detection of the difference between the pre- and post-analysis. RESULTS: On the basis of the OSDI questionnaire, the study population was divided into severe (61.1%), moderate (5.5%), and mild (16.6%) dry-eye symptoms. OSDI score was significantly reduced after HPpSIS (p<0.05). BUT and TMH values also ameliorated after HPpSIS (p>0.05), although not significantly. The lipid layer improved statistically (p<0.05) and correlated positively with OSDI grading. The variability of presentation in the numerical distribution before and after therapy suggests poor test sensitivity. CONCLUSIONS: HPpSIS showed a positive effect in reducing OSDI scores and ameliorating tear film quality. The possibility of an endogenous HPpSIS-induced NGF should be taken into account in dry-eye therapy.

Creation of a novel synthetic amniotic fluid for use in fetal therapy with in vitro testing on human amniotic membranes.

BACKGROUND: Normal saline or lactated Ringer's solutions are usually infused at the time of fetal interventions; however, the effect of these fluids on the amniotic membranes has never been assessed. Given both the significant differences between the composition of normal saline solution, lactated Ringer's solution, and amniotic fluid and the significant risk of prematurity after fetal interventions, an investigation is warranted. OBJECTIVE: This study aimed to evaluate the effect of current amnioinfusion fluids on the human amnion compared with a novel synthetic amniotic fluid. STUDY DESIGN: Amniotic epithelial cells from term placentas were isolated and cultured per protocol. A synthetic amniotic fluid was created with similar electrolyte, pH, albumin, and glucose concentrations to human amniotic fluid, termed "Amnio-well." The cultured human amniotic epithelium was exposed to normal saline solution, lactated Ringer's solution, and Amnio-well. As a control, 1 group of cells remained in culture media. Cells were evaluated for apoptosis and necrosis. A second analysis to examine if cells could be "rescued" was performed, wherein the cells were allowed to remain in the culture media for an additional 48 hours after amnioinfusion. Subsequently, tissue testing with human amniotic membrane explants was evaluated similarly. Immunofluorescent intensity studies were undertaken to evaluate reactive oxygen species-mediated cell damage. Real-time quantitative polymerase chain reaction was used to evaluate gene expression in apoptotic pathways. RESULTS: With simulated amnioinfusion, 44%, 52%, and 89% of amniotic epithelial cells were alive after exposure to normal saline solution, lactated Ringer's solution, and Amnio-well, respectively, compared with 85% in control (P<.001). After amnioinfusion and attempted cell rescue, 21%, 44%, 94%, and 88% of cells were alive after exposure to normal saline solution, lactated Ringer's solution, Amnio-well, and control, respectively (P<.001). In simulated amnioinfusion with full-thickness tissue explants, 68%, 80%, 93%, and 96% of cells were viable in normal saline solution, lactated Ringer's solution, Amnio-well, and control, respectively (P<.001). In culture, reactive oxygen species production was higher in normal saline solution, lactated Ringer's solution, and Amnio-well than in control (4.9-, 6.6-, and 1.8-fold higher, respectively, P<.001); however, this could be mitigated in Amnio-well by adding ulin-A-statin and ascorbic acid. Gene expression data revealed abnormal signaling in the p21 and BCL2/BAX pathways with normal saline solution compared with control (P=.006 and P=.041); changes were not seen with Amnio-well. CONCLUSION: In vitro, normal saline and lactated Ringer's solutions caused increased amniotic membrane reactive oxygen species and cell death. The use of a novel fluid similar to human amniotic fluid led to the normalization of cellular signaling and less cell death.

Enhanced presence of serotonin in nasal cavity after autologous stimulation.

OBJECTIVE: Serotonin, which is a vasoactive amine, is an important neurotransmitter and is involved in many behavioral and psychological phenomena, such as pain, appetite, mood, and sleep. The primary purpose of our study was to investigate the effect of high-pressure administration of sterile physiological saline isotonic solution (HpPSIS) into nasal cavity and to determine the expression of the serotonin. PATIENTS AND METHODS: The study was made in two branches, the previous with 14 volunteers, the subsequent study with 40 patients with mild anxiety disorder. The middle third of the inferior turbinate epithelial cells on the right nostril was scraped using a sterile curette and indicated as (pre), then, a spray of sterilized isotonic solution at high pressure on the left nostril was delivered, and 5 minutes later a similar stimulation was delivered on the same nostril. The stimulation was made with a specific spray dispenser. The middle third of the inferior turbinate epithelial cells on the left nostril was scraped using a sterile curette and indicated as (post). Then, based on the first part of our study, we started the second part and gave a treatment on forty new patients with anxiety disorder. RESULTS: The results of these studies highlight the possibility of endogenous enhancement of serotonin by stimulation of mast cells. In the first part of the study, Serotonin significantly increased in protein extracts after treatment (64.35±5.33 vs. 10.97±2.17; unpaired two tailed t-test, t=9.8, df=24, p≤0.0001; F=6.035; DFn=12; DFd=12). In the second part of the study, in patients treated with HpPSIS, we observed improvement of mood, after one, two and three months, with a statistically significant reduction of DASS-21, while no reduction was observed in control patients, treated with normal pressure commercial spray. CONCLUSIONS: This pilot study showed that the topical treatment of HpPHIS increases serotonin levels in nasal cavity. The observation reported in this study opens the way to a new valid strategy to enhance the level of endogenous serotonin. We observed a significant improvement of ASI on patients during HpPHIS therapy.

Effect of balanced crystalloids versus saline on urinary biomarkers of acute kidney injury in critically ill adults.

BACKGROUND: Recent trials have suggested use of balanced crystalloids may decrease the incidence of major adverse kidney events compared to saline in critically ill adults. The effect of crystalloid composition on biomarkers of early acute kidney injury remains unknown. METHODS: From February 15 to July 15, 2016, we conducted an ancillary study to the Isotonic Solutions and Major Adverse Renal Events Trial (SMART) comparing the effect of balanced crystalloids versus saline on urinary levels of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) among 261 consecutively-enrolled critically ill adults admitted from the emergency department to the medical ICU. After informed consent, we collected urine 36 ± 12 h after hospital admission and measured NGAL and KIM-1 levels using commercially available ELISAs. Levels of NGAL and KIM-1 at 36 ± 12 h were compared between patients assigned to balanced crystalloids versus saline using a Mann-Whitney U test. RESULTS: The 131 patients (50.2%) assigned to the balanced crystalloid group and the 130 patients (49.8%) assigned to the saline group were similar at baseline. Urinary NGAL levels were significantly lower in the balanced crystalloid group (median, 39.4 ng/mg [IQR 9.9 to 133.2]) compared with the saline group (median, 64.4 ng/mg [IQR 27.6 to 339.9]) (P < 0.001). Urinary KIM-1 levels did not significantly differ between the balanced crystalloid group (median, 2.7 ng/mg [IQR 1.5 to 4.9]) and the saline group (median, 2.4 ng/mg [IQR 1.3 to 5.0]) (P = 0.36). CONCLUSIONS: In this ancillary analysis of a clinical trial comparing balanced crystalloids to saline among critically ill adults, balanced crystalloids were associated with lower urinary concentrations of NGAL and similar urinary concentrations of KIM-1, compared with saline. These results suggest only a modest reduction in early biomarkers of acute kidney injury with use of balanced crystalloids compared with saline. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT02444988 . Date registered: May 15, 2015.

Protective efficacy of dinitrosyl iron complexes with reduced glutathione in cardioplegia and reperfusion.

Disturbed homeostasis of nitric oxide (NO) is one of the causes of myocardial ischemia/reperfusion (I/R) injury during open-heart surgery. This study was designed to explore mechanisms of action of dinitrosyl iron complexes with reduced glutathione ({(GS-)2Fe+(NO+)2}+, DNIC-GS) added to crystalloid cardioplegia or reperfusion solution in isolated working rat hearts. Hearts of male Wistar rats were subjected to cardioplegic arrest by St. Thomas' Hospital cardioplegic solution (STH) and normothermic global ischemia followed by reperfusion. DNIC-GS were used with STH or during early reperfusion. Lactate dehydrogenase (LDH) activity in the coronary effluent and myocardial contents of adenine nucleotides, phosphocreatine, and lactate were determined spectrophotometrically. Reactive oxygen species (ROS) formation in the coronary effluent and myocardial DNIC content was assessed by EPR technique. Cardioplegia or reperfusion with DNIC-GS significantly improved recovery of coronary flow and cardiac function compared with control. Carboxy-[2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidozoline-1-oxy-3-oxide] (C-PTIO), a selective NO scavenger, reduced/abolished protective action of DNIC-GS. Enhanced recovery of cardiac function with DNIC-GS reduced LDH release in the coronary effluent, augmented recovery of myocardial energy state, and decreased formation of ROS-generating systems at reperfusion. Beneficial effects of DNIC-GS were related to the transfer of [Fe(NO)2] cores to thiol groups of myocardial proteins to form intracellular DNIC pools. The study concluded that DNIC-GS is a promising adjunct agent for metabolic and antioxidant protection of the heart during cardioplegic arrest and reperfusion.

Renal outcome after radical cystectomy and urinary diversion performed with restrictive hydration and vasopressor administration in the frame of an enhanced recovery program: A follow-up study of a randomized clinical trial.

OBJECTIVE: To determine whether a restrictive perioperative fluid management in the context of an enhanced recovery after surgery program for radical cystectomy and urinary diversion affects renal function, as fluid restriction and the use of vasopressors have been linked to impaired tissue perfusion, potentially resulting in renal dysfunction. METHODS: We followed 166 patients initially included in a randomized clinical trial and equally allocated to receive a continuous norepinephrine administration combined with 1ml/kg/h initially, and after cystectomy 3ml/kg/h crystalloid infusion (intervention group, n = 83), or a standard crystalloid infusion of 6ml/kg/h throughout surgery (control group, n = 83). All patients followed our institutional enhanced recovery after surgery program. We prospectively assessed renal function (plasma creatinine values and estimated glomerular filtration rate Chronic Kidney Disease Epidemiology Collaboration equation) postoperatively. Decreased renal function was defined as a decrease in glomerular filtration rate is greater than 20% compared to preoperative values. RESULTS: There was no significant difference in renal function between the groups postoperatively at any time point after discharge: diabetes mellitus (HR = 2.81 [95% CI: 1.48-5.36]; P = 0.002), preoperative estimated glomerular filtration rate (HR = 1.02 [95% CI: 1.00-1.03]; P = 0.007), and age (OR = 1.03 [95% CI: 11.00-1.06]; P = 0.038) were negative predictors for renal deterioration. CONCLUSION: Postoperative renal function evolution was similar in patients receiving restrictive hydration with norepinephrine administration when compared to liberal hydration intraoperatively, suggesting that there is no influence of fluid management and administration of vasopressors on mid-term renal function.

Fluid transport by the cornea endothelium is dependent on buffering lactic acid efflux.

Maintenance of corneal hydration is dependent on the active transport properties of the corneal endothelium. We tested the hypothesis that lactic acid efflux, facilitated by buffering, is a component of the endothelial fluid pump. Rabbit corneas were perfused with bicarbonate-rich (BR) or bicarbonate-free (BF) Ringer of varying buffering power, while corneal thickness was measured. Perfusate was collected and analyzed for lactate efflux. In BF with no added HEPES, the maximal corneal swelling rate was 30.0 ± 4.1 µm/h compared with 5.2 ± 0.9 µm/h in BR. Corneal swelling decreased directly with [HEPES], such that with 60 mM HEPES corneas swelled at 7.5 ± 1.6 µm/h. Perfusate [lactate] increased directly with [HEPES]. Similarly, reducing the [HCO3 (-)] increased corneal swelling and decreased lactate efflux. Corneal swelling was inversely related to Ringer buffering power (ß), whereas lactate efflux was directly related to ß. Ouabain (100 µM) produced maximal swelling and reduction in lactate efflux, whereas carbonic anhydrase inhibition and an monocarboxylic acid transporter 1 inhibitor produced intermediate swelling and decreases in lactate efflux. Conversely, 10 µM adenosine reduced the swelling rate to 4.2 ± 0.8 µm/h and increased lactate efflux by 25%. We found a strong inverse relation between corneal swelling and lactate efflux (r = 0.98, P < 0.0001). Introducing lactate in the Ringer transiently increased corneal thickness, reaching a steady state (0 ± 0.6 µm/h) within 90 min. We conclude that corneal endothelial function does not have an absolute requirement for bicarbonate; rather it requires a perfusing solution with high buffering power. This facilitates lactic acid efflux, which is directly linked to water efflux, indicating that lactate flux is a component of the corneal endothelial pump.

Haemostasis monitored in stored red blood cells, plasma and platelet concentrates in the proportion of 4 :  4 :  1 diluted with crystalloids and colloids.

The aim of this in-vitro study was to evaluate haemostasis analysed with thromboelastometry and blood gas and blood count variables, in stored blood components and the effects after dilution with Ringer[Combining Acute Accent]s acetate, albumin and hydroxyethyl starch (HES). Aliquots from stored red blood cells, plasma and platelet concentrates were mixed in the proportion of 4 : 4 : 1 and analysed with rotational thromboelastometry (ROTEM), blood count [haemoglobin (Hb), haematocrit, platelet count] and blood gas (pH, calcium, sodium, potassium, glucose levels). The blood mix was thereafter diluted 20 and 33% with Ringer's acetate, albumin or HES. The stored blood component mix in a ratio of 4 : 4 : 1 had a low pH (7.11 ±â€Š0.03, mean ±â€Šstandard deviation), nonmeasurable calcium level, and high concentrations of sodium, potassium and glucose but ROTEM curves within normal range after recalcification. With Ringer's acetate dilution, the ROTEM variables changed almost linearly with increasing dilution volume. When albumin was used in the 33% dilution, the clot firmness of the fibrin clot (FibTEM) was further reduced, and with HES dilution, there was a pronounced impairment. The stored blood mix had a low pH and calcium level, both of which might have a significant influence on the coagulation process but normal ROTEM curves after recalcification. Dilution with Ringer's acetate and albumin resulted in moderate deterioration, while dilution with HES showed severely impaired haemostasis.

Pyruvate alleviates lipid peroxidation and multiple-organ dysfunction in rats with hemorrhagic shock.

OBJECTIVE: Pyruvate can reduce lipid peroxidation, which plays a critical role in organ injury, in various models. However, it is not fully understood if this inhibition occurs in resuscitation of hemorrhagic shock (HS). This study examines effects of pyruvate Ringer solution (PR) in this respect in rats. METHODS: Rats, subjected to 45% blood loss, were randomly allocated to the 3 groups (n = 18): HS with no fluid resuscitation (group NR), HS resuscitated with lactated Ringer solution (LR) (group LR), and HS resuscitated with PR (group PR). Mean arterial pressure, plasma levels of thiobarbituric acid reactive substances (TBARS), and superoxide dismutase were measured at various time points until 360 minutes after hemorrhage. Visceral organs were harvested at the end for evaluations of the TBARS, antioxidant enzyme, and tissue water content. Other 54 rats with identical procedures without sampling were documented for 24-hour survival rates (n = 18) after fluid resuscitation. RESULTS: Pyruvate Ringer solution significantly increased mean arterial pressure and decreased blood TBARS levels after lethal HS. It also reduced TBARS concentrations and glutathione peroxidase activities but significantly enhanced glutathione reductase activities in most organs and greatly improved the ratios of reduced glutathione over oxidized glutathione in various organs in group PR, compared to group LR. Furthermore, PR significantly improved various organ function and water contents relative to LR. Group PR showed a more than 2-fold higher 24-hour survival rate of group LR. CONCLUSIONS: Pyruvate Ringer solution alleviated organ edema and injury and prompted survival partially through inhibition of lipid peroxidation in various organs in severe HS rats.

Modeling non-linear kinetics of hyperpolarized [1-(13)C] pyruvate in the crystalloid-perfused rat heart.

Hyperpolarized (13)C MR measurements have the potential to display non-linear kinetics. We have developed an approach to describe possible non-first-order kinetics of hyperpolarized [1-(13)C] pyruvate employing a system of differential equations that agrees with the principle of conservation of mass of the hyperpolarized signal. Simultaneous fitting to a second-order model for conversion of [1-(13)C] pyruvate to bicarbonate, lactate and alanine was well described in the isolated rat heart perfused with Krebs buffer containing glucose as sole energy substrate, or glucose supplemented with pyruvate. Second-order modeling yielded significantly improved fits of pyruvate-bicarbonate kinetics compared with the more traditionally used first-order model and suggested time-dependent decreases in pyruvate-bicarbonate flux. Second-order modeling gave time-dependent changes in forward and reverse reaction kinetics of pyruvate-lactate exchange and pyruvate-alanine exchange in both groups of hearts during the infusion of pyruvate; however, the fits were not significantly improved with respect to a traditional first-order model. The mechanism giving rise to second-order pyruvate dehydrogenase (PDH) kinetics was explored experimentally using surface fluorescence measurements of nicotinamide adenine dinucleotide reduced form (NADH) performed under the same conditions, demonstrating a significant increase of NADH during pyruvate infusion. This suggests a simultaneous depletion of available mitochondrial NAD(+) (the cofactor for PDH), consistent with the non-linear nature of the kinetics. NADH levels returned to baseline following cessation of the pyruvate infusion, suggesting this to be a transient effect.

Crystalloid podocytopathy with focal segmental glomerulosclerosis in PCM: a case report.

BACKGROUND: Crystalloid podocytopathy with focal segmental glomerulosclerosis in plasma cell myeloma (PCM) is rare. CASE PRESENTATION: We present a case of crystalline deposition in the bone marrow (BM) and various renal cells with only proteinuria as a symptom. As workup for proteinuria, a renal biopsy sample was obtained. EM showed multiple crystalline depositions in renal tubular cells and podocytes. Focal segmental glomerulosclerosis with crystalloid podocytopathy was diagnosed. Because monoclonal gammopathy was detected in the serum and urine, a BM study was also performed. Plasma cells with needle-shaped inclusion bodies were observed. The crystalline deposits in the plasma cells and podocytes were positive for Masson's trichrome and kappa light-chain staining. These findings indicated that the crystalline deposits originated from paraprotein. The case showed a rare process of focal segmental glomerulosclerosis via crystalline deposition in podocytes in plasma cell myeloma. CONCLUSIONS: Crystalloid podocytopathy is a likely cause of renal damage such as FSGS in PCM, although it is an uncommon mechanism for myeloma kidney.

Crystalloids in apparent autophagic plastids: remnants of plastids or peroxisomes?

Plant macroautophagy is carried out by autophagosome-type organelles. Recent evidence suggests that plastids also can carry out macroautophagy. The double membrane at the surface of plastids apparently invaginates, forming an intraplastidial space. This space contains a portion of cytoplasm that apparently becomes degraded. Here we report, in Tillandsia sp. and Aechmaea sp., the presence of almost square or diamond-shaped crystalloids inside what seems the intraplastidial space of autophagous plastids. The same type of crystalloids were observed in chloroplasts and other plastids, but were not found in the cytoplasm or the vacuole. Peroxisomes contained smaller and more irregularly shaped crystalloids compared to the ones observed in 'autophagous' plastids. It is hypothesized that plastids are able to sequester chloroplasts and other plastids.

Guanylin activates Cl(-) secretion into the lumen of seawater eel intestine via apical Cl(-) channel under simulated in vivo conditions.

Guanylin (GN) action on seawater eel intestine was examined under simulated in vivo conditions, where isotonic luminal fluid has low NaCl and high MgSO4 (MgSO4 Ringer). In Ussing chamber, MgSO4 Ringer induced serosa-negative potential difference (PD) even after bumetanide treatment, which is due to the higher paracellular Na(+) permeability over Cl(-), as confirmed by the replacement by MgCl2 (no Cl(-) gradient) or Na2SO4 Ringer (no Na(+) gradient). Luminal GN reversed serosa-negative PD, probably by enhancing Cl(-) secretion into the lumen, as the GN effect was blocked by apical Cl(-) channel blockers [diphenylamine-2-carboxylic acid (DPC), 5-nitro-2-(3-phenylpropylamino) benzoic acid, glibenclamide but not cystic fibrosis transmembrane regulator (CFTR)inh-172] or replacement of luminal fluid by MgCl2 Ringer. The blockers' effect was undetectable when normal Ringer was on both sides. In the sac preparation, NaCl secretion occurred into the lumen (Na(+) > Cl(-)), and GN further enhanced Cl(-) secretion (Cl(-) > Na(+)), resulting in water secretion. These GN effects were also blocked by DPC. Quantitative analyses showed that isotonic NaCl is absorbed when luminal fluid is normal Ringer, but, when luminal fluid is MgSO4 Ringer, hypertonic NaCl, almost equivalent to seawater, is secreted into the lumen after GN. These results indicate that GN stimulates the secretion of hypertonic NaCl into the lumen of seawater eel intestine, like rectal gland of marine elasmobranchs, to get rid of excess NaCl although marine teleost intestine is thought to have only absorptive-type cells with a unique Na-K-Cl cotransport system. The secreted NaCl may activate the cotransport system and further help absorb water in the final segment of seawater eel intestine.

Isotonic intravenous maintenance fluid reduces hospital acquired hyponatremia in young children with central nervous system infections.

OBJECTIVE: To find the appropriate type of intravenous fluid (isotonic vs. hypotonic saline in 5 % dextrose) for empiric maintenance fluid therapy in children with central nervous system (CNS) infections that reduces the incidence of hospital acquired hyponatremia. METHODS: This blinded randomized controlled trial included hospitalized children aged 3 mo to 5 y with suspected CNS infections requiring intravenous maintenance fluid for at least 24 h. The subjects were randomized to receive 0.9 % saline (Group-A), 0.45 % saline (Group-B) and 0.18 % saline (Group-C) at standard maintenance rate. The outcome measures were proportion of patients developing hyponatremia (serum sodium < 135 mmol/L) after 24 h and serum sodium values at 6, 12, 18, 24 h of receiving maintenance fluids. RESULTS: Of the 92 patients enrolled, 31, 30 and 31 patients were randomized to Group A, B and C, respectively. Majority (60.7 %) of the patients in Group-C developed hyponatremia compared with 7.1 % of the children in Group-A and 46.1 % in Group-B. During first 24 h of fluid administration successive fall in the serum sodium values was observed in patients receiving hypotonic fluids. The risk of developing hyponatremia was nearly 6½ (95 % confidence interval (CI) 1.6-26) to 8.5 (95 % CI 2.16-33.39) times more in patients who received hypotonic saline compared to those who received isotonic saline. CONCLUSIONS: Administration of 0.9 % saline in 5 % dextrose as intravenous maintenance fluid in children with CNS infection leads to significantly less incidence of hyponatremia when compared to that with hypotonic fluids.

Why crystalloids will do the job in the operating room.

The current trend in anaesthesia is to choose crystalloid over colloid fluids for volume replacement in the operating room. Outcome-oriented studies and kinetic analyses have recently provided more insight into how crystalloid infusions should be managed. These fluids have a much better short-term effect on the plasma volume than previously believed. Their efficiency (i.e. the plasma volume expansion divided by the infused volume) is 50-80% as long as an infusion continues, while this fraction increases to 100% when the arterial pressure has dropped. Elimination is very slow during surgery, and amounts to only 10% of that recorded in conscious volunteers. Capillary refill further reduces the need for crystalloid fluid when bleeding occurs. These four factors limit the need for large volumes of crystalloid fluid during surgery. Adverse effects associated with crystalloid fluids mainly include prolonged gastrointestinal recovery time, which occurs when > 3 L has been infused. Clinicians who do not want to prolong the length of the hospital stay by 1-2 days due to such problems may use colloid fluid selectively, but calculations show that the therapeutic window for colloids is quite narrow. Inflammation is likely to decrease the fluid efficiency of colloid fluids, while its effect on crystalloids is unclear. However, some recent evidence suggests that inflammation accelerates the turnover of crystalloid fluid as well.

Role of the glycocalyx in fluid management: Small things matter.

Intravenous fluid therapy and perception of volume effects are often misunderstood. The pharmacokinetical difference between colloids and crystalloids depends on the condition of the vascular permeability barrier. Its functioning is still largely based on Starling's principle from 1896, realising that transport of fluid to and from the interstitial space follows the balance between opposing oncotic and hydrostatic pressures. In the past decade, the endothelial glycocalyx, located on the luminal side of healthy vasculature, has increasingly been taken into consideration around models of transvascular fluid filtration. While crystalloids can freely pass through the glycocalyx, colloids are held back in the vasculature by this structure. This is reflected by a markedly higher intravascular persistence of isooncotic colloids (80-100%) versus crystalloids (around 20%), at least as long as the glycocalyx is intact. Protecting this structure in surgical practice means limiting the surgical trauma and avoiding intravascular hypervolemia.

Balanced versus unbalanced salt solutions: what difference does it make?

BACKGROUND: The infusion of crystalloid solutions is a fundamental part of the management of critically ill patients. These solutions are used to maintain the balance of water and essential electrolytes and replace losses when patients have limited gastrointestinal intake. They also act as carriers for intravenous infusion of medication and red cells. The most commonly used solution, 0.9% saline, has equal concentrations of Na(+) and Cl(-) even though the plasma concentration of Na(+) normally is 40 meq/L higher than that of Cl(-). The use of this fluid thus can produce a hyperchloremic acidosis in a dose-dependent manner, but it is not known whether this has clinical significance. APPROACH: The first part of this article deals with the significance of Na(+) and Cl(-) in normal physiology. This begins with examination of their roles in the regulation of osmolality, acid-base balance, and generation of electrochemical gradients and why the concentration of Cl(-) normally is considerably lower than that of Na(+). The next part deals with how their concentrations are regulated by the gastrointestinal tract and kidney. Based on the physiology, it would seem that solutions in which the concentration of Na(+) is "balanced" by a substance other than Cl(-) would be advantageous. The final part examines the evidence to support that point. CONCLUSIONS: There are strong observational data that support the notion that avoiding an elevated Cl(-) concentration or using fluids that reduce the rise in Cl(-) reduces renal dysfunction, infections, and possibly even mortality. However, observational studies only can indicate an association and cannot indicate causality. Unfortunately, randomized trials to date are far too limited to address this crucial issue. What is clear is that appropriate randomized trials will require very large populations. It also is not known whether the important variable is the concentration of Cl(-), the difference in concentrations of Na(+) and Cl(-), or the total body mass of Cl(-).

Plasma volume expansion with 5% albumin compared to Ringer's acetate during normal and increased microvascular permeability in the rat.

BACKGROUND: It is believed that the effectiveness of colloids as plasma volume expanders is dependent on the endothelial permeability for macromolecules. The objective of this study was to test the hypothesis that the plasma volume expanding effect of 5% albumin relative to that of a crystalloid solution is reduced if microvascular permeability is increased. METHODS: A control group was resuscitated with either 5% albumin (8 ml/kg) or Ringer's acetate (36 ml/kg) immediately after a hemorrhage of 8 ml/kg (n = 29). In a second group, permeability was increased by inducing sepsis through cecal ligation and incision (n = 28). Three hours after cecal ligation and incision, the animals were resuscitated with either 5% albumin in a ratio of 1:1 relative to the volume of lost plasma, or Ringer's acetate in a ratio of 4.5:1. RESULTS: In the hemorrhage group, plasma volumes at 15 min after resuscitation with albumin or Ringer's acetate had increased by 9.8 ± 2.6 ml/kg (mean ± SD) and 7.4 ± 2.9 ml/kg and were similar at 2 and 4 h. Plasma volume 3 h after cecal ligation and incision had decreased by approximately 7 ml/kg, and at 15 min after resuscitation with albumin or Ringer's acetate it had increased by 5.7 ± 2.9 and 2.4 ± 3.0 ml/kg, respectively (P < 0.05). At 2 and 4 h after resuscitation, plasma volumes did not differ between the groups. CONCLUSION: This study does not support the hypothesis that the plasma-volume-expanding effect of albumin relative to that of crystalloids is decreased under conditions characterized by increased permeability.

Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect.

Removal of plasma proteins from perfusates increases vascular permeability. The common interpretation of the action of albumin is that it forms part of the permeability barrier by electrostatic binding to the endothelial glycocalyx. We tested the alternate hypothesis that removal of perfusate albumin in rat venular microvessels decreased the availability of sphingosine-1-phosphate (S1P), which is normally carried in plasma bound to albumin and lipoproteins and is required to maintain stable baseline endothelial barriers (Am J Physiol Heart Circ Physiol 303: H825-H834, 2012). Red blood cells (RBCs) are a primary source of S1P in the normal circulation. We compared apparent albumin permeability coefficients [solute permeability (Ps)] measured using perfusates containing albumin (10 mg/ml, control) and conditioned by 20-min exposure to rat RBCs with Ps when test perfusates were in RBC-conditioned protein-free Ringer solution. The control perfusate S1P concentration (439 ± 46 nM) was near the normal plasma value at 37 °C and established a stable baseline Ps (0.9 ± 0.4 × 10(-6) cm/s). Ringer solution perfusate contained 52 ± 8 nM S1P and increased Ps more than 10-fold (16.1 ± 3.9 × 10(-6) cm/s). Consistent with albumin-dependent transport of S1P from RBCs, S1P concentrations in RBC-conditioned solutions decreased as albumin concentration, hematocrit, and temperature decreased. Protein-free Ringer solution perfusates that used liposomes instead of RBCs as flow markers failed to maintain normal permeability, reproducing the "albumin effect" in these mammalian microvessels. We conclude that the albumin effect depends on the action of albumin to facilitate the release and transport of S1P from RBCs that normally provide a significant amount of S1P to the endothelium.