Crystalloids versus colloids for goal-directed fluid therapy in major surgery

INTRODUCTION: Perioperative hypovolemia arises frequently and contributes to intestinal hypoperfusion and subsequent postoperative complications. Goal-directed fluid therapy might reduce these complications. The aim of this study was to compare the effects of goal-directed administration of crystalloids and colloids on the distribution of systemic, hepatosplanchnic, and microcirculatory (small intestine) blood flow after major abdominal surgery in a clinically relevant pig model. METHODS: Twenty-seven pigs were anesthetized and mechanically ventilated and underwent open laparotomy. They were randomly assigned to one of three treatment groups: the restricted Ringer lactate (R-RL) group (n = 9) received 3 mL/kg per hour of RL, the goal-directed RL (GD-RL) group (n = 9) received 3 mL/kg per hour of RL and intermittent boluses of 250 mL of RL, and the goal-directed colloid (GD-C) group (n = 9) received 3 mL/kg per hour of RL and boluses of 250 mL of 6% hydroxyethyl starch (130/0.4). The latter two groups received a bolus infusion when mixed venous oxygen saturation was below 60% ('lockout' time of 30 minutes). Regional blood flow was measured in the superior mesenteric artery and the celiac trunk. In the small bowel, microcirculatory blood flow was measured using laser Doppler flowmetry. Intestinal tissue oxygen tension was measured with intramural Clark-type electrodes. RESULTS: After 4 hours of treatment, arterial blood pressure, cardiac output, mesenteric artery flow, and mixed oxygen saturation were significantly higher in the GD-C and GD-RL groups than in the R-RL group. Microcirculatory flow in the intestinal mucosa increased by 50% in the GD-C group but remained unchanged in the other two groups. Likewise, tissue oxygen tension in the intestine increased by 30% in the GD-C group but remained unchanged in the GD-RL group and decreased by 18% in the R-RL group. Mesenteric venous glucose concentrations were higher and lactate levels were lower in the GD-C group compared with the two crystalloid groups. CONCLUSIONS: Goal-directed colloid administration markedly increased microcirculatory blood flow in the small intestine and intestinal tissue oxygen tension after abdominal surgery. In contrast, goal-directed crystalloid and restricted crystalloid administrations had no such effects. Additionally, mesenteric venous glucose and lactate concentrations suggest that intestinal cellular substrate levels were higher in the colloid-treated than in the crystalloid-treated animals. These results support the notion that perioperative goal-directed therapy with colloids might be beneficial during major abdominal surgery.

Postoperative splanchnic blood flow redistribution in response to fluid challenges in the presence and absence of endotoxemia in a porcine model

We hypothesized that fluid administration may increase regional splanchnic perfusion after abdominal surgery-even in the absence of a cardiac stroke volume (SV) increase and independent of accompanying endotoxemia. Sixteen anesthetized pigs underwent abdominal surgery with flow probe fitting around splanchnic vessels and carotid arteries. They were randomized to continuous placebo or endotoxin infusion, and when clinical signs of hypovolemia (mean arterial pressure, <60 mmHg; heart rate, >100 beats · min(-1); urine production, <0.5 mL · kg(-1) · h(-1); arterial lactate concentration, >2 mmol · L(-1)) and/or low pulmonary artery occlusion pressure (target 5-8 mmHg) were present, they received repeated boli of colloids (50 mL) as long as SV increased 10% or greater. Stroke volume and regional blood flows were monitored 2 min before and 30 min after fluid challenges. Of 132 fluid challenges, 45 (34%) resulted in an SV increase of 10% or greater, whereas 82 (62%) resulted in an increase of 10% or greater in one or more of the abdominal flows (P < 0.001). During blood flow redistribution, celiac trunk (19% of all measurements) and hepatic artery flow (15%) most often decreased, whereas portal vein (10%) and carotid artery (7%) flow decreased less frequently (P = 0.015, between regions). In control animals, celiac trunk (30% vs. 9%, P = 0.004) and hepatic artery (25% vs. 11%, P = 0.040) flow decreased more often than in endotoxin-infused pigs. Accordingly, blood flow redistribution is a common phenomenon in the postoperative period and is only marginally influenced by endotoxemia. Fluid management based on SV changes may not be useful for improving regional abdominal perfusion.

Protein and lipid binding parameters in rainbow trout (Oncorhynchus mykiss) blood and liver fractions to extrapolate from an in vitro metabolic degradation assay to in vivo bioaccumulation potential of hydrophobic organic chemicals

Binding of hydrophobic chemicals to colloids such as proteins or lipids is difficult to measure using classical microdialysis methods due to low aqueous concentrations, adsorption to dialysis membranes and test vessels, and slow kinetics of equilibration. Here, we employed a three-phase partitioning system where silicone (polydimethylsiloxane, PDMS) serves as a third phase to determine partitioning between water and colloids and acts at the same time as a dosing device for hydrophobic chemicals. The applicability of this method was demonstrated with bovine serum albumin (BSA). Measured binding constants (K(BSAw)) for chlorpyrifos, methoxychlor, nonylphenol, and pyrene were in good agreement with an established quantitative structure-activity relationship (QSAR). A fifth compound, fluoxypyr-methyl-heptyl ester, was excluded from the analysis because of apparent abiotic degradation. The PDMS depletion method was then used to determine partition coefficients for test chemicals in rainbow trout (Oncorhynchus mykiss) liver S9 fractions (K(S9w)) and blood plasma (K(bloodw)). Measured K(S9w) and K(bloodw) values were consistent with predictions obtained using a mass-balance model that employs the octanol-water partition coefficient (K(ow)) as a surrogate for lipid partitioning and K(BSAw) to represent protein binding. For each compound, K(bloodw) was substantially greater than K(S9w), primarily because blood contains more lipid than liver S9 fractions (1.84% of wet weight vs 0.051%). Measured liver S9 and blood plasma binding parameters were subsequently implemented in an in vitro to in vivo extrapolation model to link the in vitro liver S9 metabolic degradation assay to in vivo metabolism in fish. Apparent volumes of distribution (V(d)) calculated from the experimental data were similar to literature estimates. However, the calculated binding ratios (f(u)) used to relate in vitro metabolic clearance to clearance by the intact liver were 10 to 100 times lower than values used in previous modeling efforts. Bioconcentration factors (BCF) predicted using the experimental binding data were substantially higher than the predicted values obtained in earlier studies and correlated poorly with measured BCF values in fish. One possible explanation for this finding is that chemicals bound to proteins can desorb rapidly and thus contribute to metabolic turnover of the chemicals. This hypothesis remains to be investigated in future studies, ideally with chemicals of higher hydrophobicity.

Biological applications of magnetic nanoparticles

In this review an overview about biological applications of magnetic colloidal nanoparticles will be given, which comprises their synthesis, characterization, and in vitro and in vivo applications. The potential future role of magnetic nanoparticles compared to other functional nanoparticles will be discussed by highlighting the possibility of integration with other nanostructures and with existing biotechnology as well as by pointing out the specific properties of magnetic colloids. Current limitations in the fabrication process and issues related with the outcome of the particles in the body will be also pointed out in order to address the remaining challenges for an extended application of magnetic nanoparticles in medicine.

Surfactant mediated adsorption of negatively charged latex particles to a cellulose surface

The adsorption of anionic, carboxyl functionalized latex particles, recharged by a cationic surfactant acting as fabric softener/conditioner, to a cellulose surface was investigated with evanescent wave video microscopy. This technique allows to monitor the deposition and release of individual particles in real-time with an excellent selectivity and sensitivity. Since the recharged particles and the conditioner compete for the free surface, the initial deposition rate and final surface coverage are found to be strongly dependent on the ratio of particle and conditioner concentrations.

Is perioperative point-of-care prothrombin time testing accurate compared to the standard laboratory test?

There is no accepted way of measuring prothrombin time without time loss for patients undergoing major surgery who are at risk of intraoperative dilution and consumption coagulopathy due to bleeding and volume replacement with crystalloids or colloids. Decisions to transfuse fresh frozen plasma and procoagulatory drugs have to rely on clinical judgment in these situations. Point-of-care devices are considerably faster than the standard laboratory methods. In this study we assessed the accuracy of a Point-of-care (PoC) device measuring prothrombin time compared to the standard laboratory method. Patients undergoing major surgery and intensive care unit patients were included. PoC prothrombin time was measured by CoaguChek XS Plus (Roche Diagnostics, Switzerland). PoC and reference tests were performed independently and interpreted under blinded conditions. Using a cut-off prothrombin time of 50%, we calculated diagnostic accuracy measures, plotted a receiver operating characteristic (ROC) curve and tested for equivalence between the two methods. PoC sensitivity and specificity were 95% (95% CI 77%, 100%) and 95% (95% CI 91%, 98%) respectively. The negative likelihood ratio was 0.05 (95% CI 0.01, 0.32). The positive likelihood ratio was 19.57 (95% CI 10.62, 36.06). The area under the ROC curve was 0.988. Equivalence between the two methods was confirmed. CoaguChek XS Plus is a rapid and highly accurate test compared with the reference test. These findings suggest that PoC testing will be useful for monitoring intraoperative prothrombin time when coagulopathy is suspected. It could lead to a more rational use of expensive and limited blood bank resources.

Microcirculatory parameters after isotonic and hypertonic colloidal fluid resuscitation in acute hemorrhagic shock

BACKGROUND: Volume resuscitation is one of the primary therapeutic goals in hemorrhagic shock, but data on microcirculatory effects of different colloidal fluid resuscitation regimen are sparse. We investigated sublingual mucosal microcirculatory parameters during hemorrhage and after fluid resuscitation with gelatin, hydroxyethyl starch, or hypertonic saline and hydroxyethyl starch in pigs. METHODS: To induce hemorrhagic shock, 60% of calculated blood volume was withdrawn. Microvascular blood flow was assessed by laser Doppler velocimetry. Microcirculatory hemoglobin oxygen saturation was measured with a tissue reflectance spectrophotometry, and side darkfield imaging was used to visualize the microcirculation and to quantify the flow quality. Systemic hemodynamic variables, systemic acid base and blood gas variables, and lactate measurements were recorded. Measurements were performed at baseline, after hemorrhage, and after fluid resuscitation with a fixed volume regimen. RESULTS: Systemic hemodynamic parameters returned or even exceeded to baseline values in all three groups after fluid resuscitation, but showed significantly higher filling pressures and cardiac output values in animals treated with isotonic colloids. Microcirculatory parameters determined in gelatin and hydroxyethyl starch resuscitated animals, and almost all parameters except microvascular hemoglobin oxygen saturation in animals treated with hypertonic saline and hydroxyethyl starch, were restored after treatment. DISCUSSION: Hemorrhaged pigs can be hemodynamically stabilized with either isotonic or hypertonic colloidal fluids. The main finding is an adequate restoration of sublingual microcirculatory blood flow and flow quality in all three study groups, but only gelatin and hydroxyethyl starch improved microvascular hemoglobin oxygen saturation, indicating some inadequate oxygen supply/demand ratio maybe due to a better restoration of systemic hemodynamics in isotonic colloidal resuscitated animals.

Synthesis of bone-like micro-porous calcium phosphate/iota-carrageenan composites by gel diffusion

Brushite and octacalcium phosphate (OCP) crystals are well-known precursors of hydroxylapatite (HAp), the main mineral found in bone. In this report, we present a new method for biomimicking brushite and OCP using single and double diffusion techniques. Brushite and OCP crystals were grown in an iota-carrageenan gel. The aggregates were analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD), infrared spectroscopy (IR) and thermal gravimetric analysis (TGA). SEM revealed different morphologies of brushite crystals from highly porous aggregates to plate-shaped forms. OCP crystals grown in iota-carrageenan showed a porous spherical shape different from brushite growth forms. The XRD method demonstrated that the single-diffusion method favors the formation of monoclinic brushite. In contrast, the double diffusion method was found to promote the formation of the triclinic octacalcium phosphate OCP phase. By combining the different parameters for crystal growth in carrageenan, such as ion concentration, gel pH and gel density, it is possible to modify the morphology of composite crystals, change the phase of calcium phosphate and modulate the amount of carrageenan inclusion in crystals. This study suggests that iota-carrageenan is a high-molecular-weight polysaccharide that is potentially applicable for controlling calcium phosphate crystallization.

Interactions between dodecyl phosphates and hydroxyapatite or tooth enamel: relevance to inhibition of dental erosion.

Tooth surface modification is a potential method of preventing dental erosion, a form of excessive tooth wear facilitated by softening of tooth surfaces through the direct action of acids, mainly of dietary origin. We have previously shown that dodecyl phosphates (DPs) effectively inhibit dissolution of native surfaces of hydroxyapatite (the type mineral for dental enamel) and show good substantivity. However, adsorbed saliva also inhibits dissolution and DPs did not augment this effect, which suggests that DPs and saliva interact at the hydroxyapatite surface. In the present study the adsorption and desorption of potassium and sodium dodecyl phosphates or sodium dodecyl sulphate (SDS) to hydroxyapatite and human tooth enamel powder, both native and pre-treated with saliva, were studied by high performance liquid chromatography-mass Spectrometry. Thermo gravimetric analysis was used to analyse residual saliva and surfactant on the substrates. Both DPs showed a higher affinity than SDS for both hydroxyapatite and enamel, and little DP was desorbed by washing with water. SDS was readily desorbed from hydroxyapatite, suggesting that the phosphate head group is essential for strong binding to this substrate. However, SDS was not desorbed from enamel, so that this substrate has surface properties different from those of hydroxyapatite. The presence of a salivary coating had little or no effect on adsorption of the DPs, but treatment with DPs partly desorbed saliva; this could account for the failure of DPs to increase the dissolution inhibition due to adsorbed saliva.

Covalent immobilisation of VEGF on plasma-coated electrospun scaffolds for tissue engineering applications.

Recent findings in the field of biomaterials and tissue engineering provide evidence that surface immobilised growth factors display enhanced stability and induce prolonged function. Cell response can be regulated by material properties and at the site of interest. To this end, we developed scaffolds with covalently bound vascular endothelial growth factor (VEGF) and evaluated their mitogenic effect on endothelial cells in vitro. Nano- (254±133 nm) or micro-fibrous (4.0±0.4 μm) poly(ɛ-caprolactone) (PCL) non-wovens were produced by electrospinning and coated in a radio frequency (RF) plasma process to induce an oxygen functional hydrocarbon layer. Implemented carboxylic acid groups were converted into amine-reactive esters and covalently coupled to VEGF by forming stable amide bonds (standard EDC/NHS chemistry). Substrates were analysed by X-ray photoelectron spectroscopy (XPS), enzyme-linked immuno-assays (ELISA) and immunohistochemistry (anti-VEGF antibody and VEGF-R2 binding). Depending on the reaction conditions, immobilised VEGF was present at 127±47 ng to 941±199 ng per substrate (6mm diameter; concentrations of 4.5 ng mm(-2) or 33.3 ng mm(-2), respectively). Immunohistochemistry provided evidence for biological integrity of immobilised VEGF. Endothelial cell number of primary endothelial cells or immortalised endothelial cells were significantly enhanced on VEGF-functionalised scaffolds compared to native PCL scaffolds. This indicates a sustained activity of immobilised VEGF over a culture period of nine days. We present a versatile method for the fabrication of growth factor-loaded scaffolds at specific concentrations.

Comparison of the in vitro effects of saline, hypertonic hydroxyethyl starch, hypertonic saline, and two forms of hydroxyethyl starch on whole blood coagulation and platelet function in dogs.

OBJECTIVE To compare the in vitro effects of hypertonic solutions and colloids to saline on coagulation in dogs. DESIGN In vitro experimental study. SETTING Veterinary teaching hospital. ANIMALS Twenty-one adult dogs. INTERVENTIONS Blood samples were diluted with saline, 7.2% hypertonic saline solution with 6% hydroxyethylstarch with an average molecular weight of 200 kDa and a molar substitution of 0.4 (HH), 7.2% hypertonic saline (HTS), hydroxyethyl starch (HES) 130/0.4 or hydroxyethyl starch 600/0.75 at ratios of 1:22 and 1:9, and with saline and HES at a ratio of 1:3. MEASUREMENTS AND MAIN RESULTS Whole blood coagulation was analyzed using rotational thromboelastometry (extrinsic thromboelastometry-cloting time (ExTEM-CT), maximal clot firmness (MCF) and clot formation time (CFT) and fibrinogen function TEM-CT (FibTEM-CT) and MCF) and platelet function was analyzed using a platelet function analyzer (closure time, CTPFA ). All parameters measured were impaired by saline dilution. The CTPFA was prolonged by 7.2% hypertonic saline solution with 6% hydroxyethylstarch with an average molecular weight of 200 kDa and a molar substitution of 0.4 (HH) and HTS but not by HES solutions. At clinical dilutions equivalent to those generally administered for shock (saline 1:3, HES 1:9, and hypertonic solutions 1:22), CTPFA was more prolonged by HH and HTS than other solutions but more by saline than HES. No difference was found between the HES solutions or the hypertonic solutions. ExTEM-CFT and MCF were impaired by HH and HTS but only mildly by HES solutions. At clinically relevant dilutions, no difference was found in ExTEM-CFT between HTS and saline or in ExTEM-MCF between HH and saline. No consistent difference was found between the 2 HES solutions but HH impaired ExTEM-CFT and MCF more than HTS. At high dilutions, FibTEM-CT and -MCF and ExTEM-CT were impaired by HES. CONCLUSIONS Hypertonic solutions affect platelet function and whole blood coagulation to a greater extent than saline and HES. At clinically relevant dilutions, only CTPFA was markedly more affected by hypertonic solutions than by saline. At high dilutions, HES significantly affects coagulation but to no greater extent than saline at clinically relevant dilutions.