Acetate- versus lactate-buffered crystalloid solutions: A systematic review with meta-analysis and trial sequential analysis.

OBJECTIVE: There is a widespread use of buffered crystalloid solutions in clinical practice. However, guidelines do not distinguish between specific types of buffered solutions and clinical equipoise exists. We aimed to assess the desirable and undesirable effects of acetate- versus lactate-buffered solutions in hospitalised patients. METHODS: We conducted a systematic review with meta-analysis and trial sequential analysis of randomised clinical trials assessing the use of acetate- versus lactate-buffered solutions for intravenous administration in hospitalised adults and children. The primary outcome was all-cause short-term mortality. We adhered to our published protocol, the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, the Cochrane Handbook and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. RESULTS: We included five RCTs enrolling 390 patients. We found no statistically significant difference in short-term mortality (random effects, risk ratio [RR] 0.29; 95% confidence interval [CI] 0.06-1.51, p = .14, I2  = 0%) or hospital length of stay (LOS) (random effects, mean difference [MD]-1.31, 95% CI -3.66 to 1.05, p = .28, I2  = 0%) between acetate- versus lactate-buffered solutions. The quality of evidence was very low. Data regarding intensive care unit LOS were reported by three trials and duration of vasopressor treatment by one trial; none of these data allowed for pooling in meta-analyses. No trials reported data on long-term mortality, health-related quality of life, adverse events, duration of mechanical ventilation or renal replacement therapy. CONCLUSION: In this systematic review, we found very low quantity and quality of evidence on the use of acetate- versus lactate-buffered solutions in hospitalised patients.

Mixing commonly used crystalloid solutions with red blood cells in five common additives does not negatively impact hemolysis, aggregometry, or deformability.

BACKGROUND: Literature is beginning to challenge the belief that it is unsafe to coinfuse red blood cells (RBCs) with solutions other than isotonic saline. We recently showed that additive-free RBCs tolerated coincubation with Plasma-Lyte or catecholamines dissolved in normal saline (NS), though 5% dextrose in water (D5W) promoted hemolysis. Herein, we evaluate the effect of coincubating crystalloids on additive-preserved RBC hemolysis, aggregation, and membrane deformability. STUDY DESIGN AND METHODS: RBCs were coincubated 5 minutes with plasma, NS, Plasma-Lyte, lactated Ringer's (LR) or D5W (1 mL PRBC +131.3 µL solution). Samples were then assessed for hemolysis (free hemoglobin), aggregation (critical shear stress [mPa]), and membrane deformability (elongation index [EI]). Significance (P ≤ .05) by t test or ANOVA with post-hoc Tukey-Kramer test. RESULTS: Additive-prepared RBCs coincubated with crystalloid instead of plasma demonstrated: (a) no increase in hemolysis as indicated by plasma free hemoglobin levels that is likely to be clinically relevant; (b) no increase, but in some cases a decrease, in aggregation as indicated by critical shear stress; and (c) in some combinations, a deterioration in deformability. When present, the deformability decrease was likely clinically insignificant in degree, and always returned to normal when the crystalloid was subsequently diluted out with plasma. CONCLUSION: Our data suggest that additive-prepared RBCs coincubated for 5 minutes with any of four common crystalloids demonstrate no clinically relevant increased lysis, increased aggregation, or decreased deformability.

Fluid Resuscitation: History, Physiology, and Modern Fluid Resuscitation Strategies.

Intravenous (IV) fluids are among the most common interventions performed in the emergency department. They are at times lifesaving, but if used recklessly can be harmful. Given their ubiquity, it is important to understand the history, physiology, and current strategies that govern the use of IV fluids during the resuscitation of the critically ill.

Lactate versus acetate buffered intravenous crystalloid solutions: a scoping review.

BACKGROUND: Buffered crystalloid solutions are increasingly recommended as first-line intravenous resuscitation fluids. However, guidelines do not distinguish between the different types of buffered solutions. The aim of this scoping review was to assess the evidence on the use of lactate- vs acetate-buffered crystalloid solutions and their potential benefits and harms. METHODS: We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. We searched PubMed, Embase, Epistemonikos, and the Cochrane Library for studies assessing the effect of lactate- vs acetate-buffered crystalloid solutions on any outcome in adult hospitalised patients. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: We included a total of 29 studies, 25 of which were clinical trials and four were observational studies. Most studies were conducted in surgical settings and indications for use were poorly described. The most commonly administered solutions were Ringer's lactate vs Ringer's acetate or Plasma-Lyte™. Outcomes included acid/base and electrolyte status; haemodynamic variables; and markers of renal and liver function, metabolism, and coagulation. Only a few studies reported patient-centred outcomes. Overall, the data provided no firm evidence for benefit or harm of either solution, and the quantity and quality of evidence were low. CONCLUSIONS: The quantity and quality of evidence on the use of different buffered crystalloid intravenous solutions were low, data were derived primarily from surgical settings, and patient-important outcomes were rarely reported; thus, the balance between benefits and harms between these solutions is largely unknown.

Population-based volume kinetics of crystalloids and colloids in healthy volunteers.

We characterized the volume kinetics of crystalloid solutions (Ringer's lactate solution and 5% dextrose water) and colloid solutions (6% tetrastarch and 10% pentastarch) by nonlinear mixed-effects modeling in healthy volunteers. We also assessed whether the bioelectrical impedance analysis parameters are significant covariates for volume kinetic parameters. Twelve male volunteers were randomly allocated to four groups, and each group received the four fluid solutions in specified sequences, separated by 1-week intervals to avoid any carryover effects. Volunteers received 40 ml/kg Ringer's lactate solution, 20 ml/kg 5% dextrose water, 1000 ml 6% tetrastarch, and 1000 ml 10% pentastarch over 1 h. Arterial blood samples were collected to measure the hemoglobin concentration at different time points. Bioelectrical impedance spectroscopy (BIS, INBODY S10, InBody CO., LTD, Seoul, Korea) was also carried out at preset time points. In total, 671 hemoglobin-derived plasma dilution data points were used to determine the volume kinetic characteristics of each fluid. The changes in plasma dilution induced by administration of crystalloid and colloid solutions were well-described by the two-volume and one-volume models, respectively. Extracellular water was a significant covariate for the peripheral volume of distribution at baseline in the volume kinetic model of Ringer's lactate solution. When the same amount was administered, the colloid solutions had ~4 times more plasma expansion effect than did the crystalloid solutions. Starches with larger molecular weights maintained the volume expansion effect longer than those with smaller molecular weights.

Conformational Transformation of pH-Responsive Hairy Cellulose NanoCrystalloids in Salt-Free Dilute Solutions.

Among biomaterials, pH-responsive nanoparticles have promising potential for overcoming nonspecific therapeutic delivery by taking advantage of the pH gradient between physiological and pathological states. This article discusses pH-dependent conformations of an organic nanoparticle that has a needle-shaped body from crystalline cellulose, sandwiched between two amorphous regions from chemically nanoengineered dicarboxylated cellulose (DCC). Computational study on a single free DCC chain elucidated that in a salt-free dilute solution, the chain undergoes a major transformation between pH ∼ 3 and ∼6.3. Through this transformation, the DCC chain nature varies from globular neutral polymer to coiled quasi-neutral polymer and finally to rodlike polyelectrolyte. Study on the particle nanostructure indicated that, at pH ∼ 3, the conformation of the amorphous regions is analogous to that of polymer brushes in poor solvents, whereas at pH ∼ 5, the conformation changes to that of quasi-neutral polymer brushes in good solvents. For pH > 6.3, the conformation transforms into that of star-like polyelectrolytes. The height of the amorphous region exhibits a regressive trend up to pH ∼ 6.3, followed by a progressive trend up to pH ∼ 10. Study on the hydrodynamic properties revealed a sharp decline in the diffusion rate as the pH varies from ∼3 to ∼5, followed by a plateau for higher pH. It was demonstrated that, at pH ∼ 3, the nanoparticle may form a coherent nanophase with a rodlike structure. These results may provide insight into designing pH-responsive nanocelluloses with a controlled expansion and diffusion coefficient.

Characterisation of aluminium release by the enFlow® fluid-warming system in crystalloids and blood products.

The use of uncoated aluminium-heated plates in an intravenous fluid-warming system has been shown to produce high levels of aluminium in Sterofundin 1/1E, a balanced crystalloid solution. However, the effect of this fluid-warming device on other balanced crystalloid solutions and blood products has not been studied. Using mass spectrometry we measured aluminium levels in Plasma-Lyte 148, compound sodium lactate solution, 4% human albumin solution, expired resuspended packed red cells and fresh frozen plasma that were pumped through an enFlow® fluid-warming system at 2 ml.min-1 . Samples were taken at baseline before heating and then at 10-min intervals up to 60 min with the system set to warm the fluids to 40 °C. High concentrations of aluminium were found for Plasma-Lyte 148 and compound sodium lactate solutions (mean (SD) 223 (0.6) µmol.l-1 and 163 (0.2) µmol.l-1 at 60 min, respectively); both concentrations were significantly greater than the United States Food and Drug Administration recommended maximum limit for aluminium in intravenous nutrition of 25 µg.l-1 (0.9 µmol.l-1 ). Lower aluminium levels were found in 4% human albumin solutions, expired resuspended red cells and fresh frozen plasma at 60 min (mean (SD) 5.7 (0.1) µmol.l-1 , 2.7 (0.0) µmol.l-1 and 2.3 (0.4) µmol.l-1 , respectively). The process allowing addition of aluminium to be added to Sterofundin 1/1E by the enFlow fluid warmer also occurs in Plasma-Lyte 148 and compound sodium lactate solutions and to a lesser degree in blood products. The exact mechanism facilitating this process and its clinical significance remain unclear.

Effect of incubation with crystalloid solutions or medications on packed red blood cells.

BACKGROUND: American Association of Blood Banks (AABB) guidelines suggest that packed red blood cells (PRBCs) be administered through a dedicated intravenous (IV) catheter. Literature supporting this broad-scope declaration are scarce. Obtaining additional IV access is painful, costly, and an infectious risk. We evaluated the effect of co-incubating PRBCs with crystalloids and medications on PRBC hemolysis, membrane deformability, and aggregation, as well as medication concentration. METHODS: PRBCs were co-incubated 5 minutes with plasma, normal saline (NS), 5% dextrose in water (D5W), Plasmalyte, epinephrine (epi), norepinephrine (norepi), dopamine (dopa), or Propofol (prop). Samples were then assessed for hemolysis (free hemoglobin, serum potassium), membrane deformability (elongation index [EI]), aggregation (smear, critical shear stress [mPa]) and drug concentration (High Performance Liquid Chromatography/Tandem Mass Spectrometry [LCMS-MS]). Significance (p ≤ 0.05) was determined by Wilcoxon-paired comparisons or Wilcoxon/Kruskall Willis with post-hoc Dunn's test. RESULTS: Compared to co-incubation with plasma: 1) co-incubation resulted in significantly increased hemolysis only when D5W as used (free hemoglobin, increased potassium); 2) EI trended lower when co-incubated with D5W and trended toward higher when co-incubated with prop; 3) aggregation was significantly lower when PRBCs co-incubated with NS, D5W, or Plasmalyte, and trended lower when co-incubated with epi, norepi, or dopa. Medication concentrations were between those predicted by distribution only in plasma and distribution through the entire intra- and extracellular space. CONCLUSION: Our data suggest that 5 minutes of PRBC incubation with isotonic crystalloids or catecholamines does not deleteriously alter PRBC hemolysis, membrane deformability, or aggregation. Co-incubation with D5W likely increases hemolysis. Propofol may promote hemolysis.

Effects of a novel low volume resuscitation solutions on coagulation and platelet function.

BACKGROUND: Novel crystalloid solutions containing polyethylene glycol polymers (PEG-20k) produce dramatic resuscitation effects but dose-dependently produce a hypocoagulative state. The objective of this study was to examine possible mechanisms of this effect. Based on previous thromboelastography data, we hypothesize the effect is largely due to platelet interactions with the polymers. METHODS: Whole citrated blood from healthy volunteers was diluted ex-vivo 10% with crystalloids and tested for coagulation and platelet function. The specific tests included prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen and von Willebrand factor (vWf) activity, thrombin generation, thromboelastography with and without platelet mapping, platelet flow cytometry, and erythrocyte sedimentation rate. FINDINGS: Fibrinogen and vWF activities, PT, and aPTT were not affected by PEG-20k dilutions. Thrombin activity was mildly suppressed with PEG-20k (TTP- 20%). Platelet mapping demonstrated significantly greater % inhibition of both ADP and arachidonic acid-induced platelet aggregation with PEG-20k, but direct ADP-activated gpIIa/IIIb (PAC1) and P-selectin (CD62P) binding site expression was not altered. Mild dose-dependent suppression of TEG-MA was seen with PEG-20k using platelet poor plasma. Erythrocyte Sedimentation Rates (ESR) were dramatically accelerated after dilution with 10% PEG-20k, which was competitively blocked by smaller PEG polymers, suggesting nonspecific PEG-20k cell binding effects. CONCLUSIONS: PEG-20k creates a mild hypocoagulative state in whole blood at concentrations ≥10%, which may be due to platelet-PEG interactions at the IIb/IIIa interface with lesser effects on fibrin polymerization. This interaction may cause a functional thrombasthenia induced by nonspecific platelet surface passivation by the PEG polymer.