Safety and efficacy of tetrastarches in surgery and trauma: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Hydroxyethyl starch (HES) 130 is a frequently used fluid to replace intravascular losses during surgery or trauma. In the past years, several trials performed in critically ill patients have raised questions regarding the safety of this product. Our aim in this meta-analysis was to evaluate the safety and efficacy of 6% HES during surgery and in trauma. METHODS: This systematic review and meta-analysis was registered at PROSPERO (CRD42018100379). We included 85 fully published articles from 1980 to June 2018 according to the protocol and three additional recent articles up to June 2020 in English, French, German, and Spanish reporting on prospective, randomised, and controlled clinical trials applying volume therapy with HES 130/0.4 or HES 130/0.42, including combinations with crystalloids, to patients undergoing surgery. Comparators were albumin, gelatin, and crystalloids only. A meta-analysis could not be performed for the two trauma studies as there was only one study that reported data on endpoints of interest. RESULTS: Surgical patients treated with HES had lower postoperative serum creatinine (P<0.001) and showed no differences in renal dysfunction, renal failure, or renal replacement therapy. Although there was practically no further difference in the colloids albumin or gelatin, the use of HES improved haemodynamic stability, reduced need for vasopressors (P<0.001), and decreased length of hospital stay (P<0.001) compared with the use of crystalloids alone. CONCLUSIONS: HES was shown to be safe and efficacious in the perioperative setting. Results of the present meta-analysis suggest that when used with adequate indication, a combination of intravenous fluid therapy with crystalloids and volume replacement with HES as colloid has clinically beneficial effects over using crystalloids only.

Per-operative fluid therapy, vasopressor and transfusion rate in DIEP-flap breast reconstruction. A series of cases / Fluidoterapia, uso de vasopresores y tasa transfusional peroperatoria en la reconstrucción mamaria con colgajo DIEP. Una serie de casos

OBJECTIVE: Anesthetic management in DIEP-flap breast reconstruction surgery may influence the appearance of postoperative complications. Fluid therapy, vasopressor use, and blood management are controversial. The aim was to audit hemodynamic management and to assess its impact on perioperative outcomes. MATERIAL AND METHODS: Sixty-seven cases of DIEP-flap breast reconstruction were reviewed. Data collected: anthropometric data; ASA score; comorbidities; timing of reconstruction (immediate/delayed), type of reconstruction (unilateral/bilateral); length of surgery; per-operative complications; per-operative fluid therapy, use of vasopressors, transfusion rate; re-intervention requirements; surgical success rate; hospital stay, and readmission rate. RESULTS: Median crystalloid infusion rate was 3.18 (2.63-3.76) ml/kg/h in the first 24 hours. Intraoperatively, colloids were administered in 35 (52%) patients at a median infusion rate of 1.40 (1.08-1.86) ml/Kg/h; 21 (60%) of them presented some postoperative complication. Hypotensive events were registered in 13 (19%) patients; 9 (69%) suffered some postoperative complication. The only vasopressor used was Ephedrine in 14 (21%) patients, at a median dose of 0 (0-6) mg. Red blood cell (RBC) transfusion was required in 18 (27%) patients. All of the patients who were transfused, 11 (61%) presented some postoperative complication. Hospital stay was 7 (7-9) days. Surgery was successful in 46 (69%) patients and readmission was necessary in 11 (16%) patients. CONCLUSIONS: Colloids administration, intraoperative hypotensive events, RBC transfusion, and delayed surgery are variables that could increase the risk of postoperative complications in our series.

OBJETIVO: El manejo anestésico en la cirugía de reconstrucción mamaria con colgajo DIEP podría influir en la aparición de complicaciones posoperatorias. La fluidoterapia, el uso de vasopresores y la tasa transfusional son motivo de controversia. Nuestro objetivo fue auditar el manejo hemodinámico y valorar su impacto en los resultados perioperatorios. MATERIAL Y MÉTODOS: Analizamos 67 pacientes programadas para reconstrucción mamaria con colgajo DIEP. Datos registrados: antropométricos; ASA; comorbilidades; momento de la reconstrucción (inmediata/diferida); tipo de reconstrucción (unilateral/bilateral); duración quirúrgica; complicaciones perioperatorias; fluidoterapia, vasopresores y tasa transfusional peroperatorios; tasa de reintervención, reingresos y éxito de la cirugía; estancia hospitalaria. RESULTADOS: La velocidad promedio de infusión de cristaloides fue de 3,18 (2,63-3,76) ml/kg/h en las primeras 24 h. Intraoperatoriamente se administraron coloides en 35 (52%) pacientes a una velocidad promedio de infusión de 1,40 (1,08-1,86) ml/kg/h, presentando complicaciones posoperatorias en 21 (60%) casos. Trece (19%) pacientes presentaron eventos hipotensivos intraoperatorios, registrándose complicaciones en 9 (69%). El único vasopresor utilizado fue la efedrina en 14 (21%) pacientes, a una dosis mediana de 0 (0-6) mg. Requirieron transfusión sanguínea 18 (27%) pacientes. Del total de pacientes transfundidos, 11 (61%) habían presentado alguna complicación posoperatoria. La cirugía fue un éxito en 46 (69%) casos. La estancia hospitalaria fue de 7 (7-9) días y el reingreso fue necesario en 11 (16%) casos. CONCLUSIONES: La administración de coloides, los eventos hipotensivos intraoperatorios, la transfusión de hemoderivados y la cirugía con reconstrucción tardía son variables que podrían incrementar el riesgo de complicaciones posoperatorias.

In Vivo Immunomodulatory Potential of Partial Purified Lectin from the Saffron Milk Cap Mushroom, Lactarius deliciosus (Agaricomycetes), against Colloidal Carbon Particles.

Mushroom compounds and biomolecules are known for their biological beneficial effects and dietary properties. Their molecules can be used in immunology for their ability to stimulate immune cells and in biotherapy of diseases. In this study, the immunomodulatory effect using carbon clearance test in vivo of partial purified lectin of Lactarius deliciosus using DEAE-Sephacyl column, with sugar affinity against galactose, methyl-ß-D-galactopyranoside and lactose, showed a significant effect on phagocytic activity and half-life of carbon particles in mice with different concentrations (5, 10, 15, and 30 mg/kg). The results showed that the immunomodulatory effect increased in low doses and decreased in high doses compared with the control group p < 0.0001. L. deliciosus lectin exerted a dose-dependent immunostimulant activity toward the reticulo-endothelial system, and phagocytic activity toward macrophages and neutrophils in spleen and liver against the colloidal carbon.

Fatal anaphylactic shock induced by intravenous gelatin colloid: a postmortem allergological work-up

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Identification and Management of Perioperative Anaphylaxis.

The authors present a case of a patient with multiple episodes of perioperative anaphylaxis. The incidence and the most common causes of perioperative anaphylaxis are reviewed. The most common causes can vary by country and the type of perioperative medications used. The unique environment and the multiple medications and substances used in the anesthesia and surgical setting that make a definitive diagnosis challenging are outlined. A systematic strategy to recognize the reaction, identify the culprit, and direct future management are demonstrated. Management of the patient experiencing perioperative anaphylaxis requires close collaboration between the anesthesia, surgical, and allergy teams.

Efficacy and safety of 20% albumin fluid loading in healthy subjects: a comparison of four resuscitation fluids.

Recently, buffered salt solutions and 20% albumin (small volume resuscitation) have been advocated as an alternative fluid for intravenous resuscitation. The relative comparative efficacy and potential adverse effects of these solutions have not been evaluated. In a randomized, double blind, cross-over study of six healthy male subjects we compared the pulmonary and hemodynamic effects of intravenous administration of 30 ml/kg of 0.9% saline, Hartmann's solution and 4% albumin, and 6 ml/kg of 20% albumin (albumin dose equivalent). Lung tests (spirometry, ultrasound, impulse oscillometry, diffusion capacity, and plethysmography), two- to three-dimensional Doppler echocardiography, carotid applanation tonometry, blood gases, serum/urine markers of endothelial, and kidney injury were measured before and after each fluid bolus. Data were analyzed with repeated measures ANOVA with effect of fluid type examined as an interaction. Crystalloids caused lung edema [increase in ultrasound B line (P = 0.006) and airway resistance (P = 0.009)], but evidence of lung injury [increased angiopoietin-2 (P = 0.019)] and glycocalyx injury [increased syndecan (P = 0.026)] was only observed with 0.9% saline. The colloids caused greater left atrial stretch, decrease in lung volumes, and increase in diffusion capacity than the crystalloids, but without pulmonary edema. Stroke work increased proportionally to increase in preload with all four fluids (R2 = 0.71). There was a greater increase in cardiac output and stroke volume after colloid administration, associated with a reduction in afterload. Hartmann's solution did not significantly alter ventricular performance. Markers of kidney injury were not affected by any of the fluids administrated. Bolus administration of 20% albumin is both effective and safe in healthy subjects. NEW & NOTEWORTHY Bolus administration of 20% albumin is both effective and safe in healthy subjects when compared with other commonly available crystalloids and colloidal solution.

Morbidity and Mortality of Crystalloids Compared to Colloids in Critically Ill Surgical Patients: A Subgroup Analysis of a Randomized Trial.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: The multicenter randomized Colloids versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was designed to test whether colloids altered mortality compared to crystalloids in the resuscitation of intensive care unit patients with hypovolemic shock. This preplanned analysis tested the same hypothesis in the subgroup of surgical patients. METHODS: The CRISTAL trial prospectively defined patients as critically ill surgical patients whenever they underwent emergency or scheduled surgery immediately before or within 24 h of intensive care unit admission and had hypovolemic shock. The primary outcome measure was death by day 28. Secondary outcome measures included death by day 90, the need for renal replacement therapy, or the need for fresh frozen plasma transfusion. RESULTS: There were 741 critically ill surgical patients, 356 and 385 in the crystalloid and colloid arm, respectively. Median (interquartile range) age was 66 (52 to 76) yr, and 484 (65.3%) patients were male. Surgery was unscheduled in 543 (73.3%) cases. Mortality by day 28 did not significantly differ for crystalloids 84 (23.6%) versus colloids 100 (26%; adjusted odds ratio, 0.86; 95% CI, 0.61 to 1.21; P = 0.768). Death by day 90 (111 [31.2%] vs. 122 [31.7%]; adjusted odds ratio, 0.97; 95% CI, 0.70 to 1.33; P = 0.919) did not significantly differ between groups. Renal replacement therapy was required for 42 (11.8%) patients in the crystalloids arm versus 49 (12.7%) in the colloids arm (P = 0.871). CONCLUSIONS: The authors found no survival benefit when comparing crystalloids to colloids in critically ill surgical patients.

Colloids versus crystalloids for fluid resuscitation in critically ill people.

BACKGROUND: Critically ill people may lose fluid because of serious conditions, infections (e.g. sepsis), trauma, or burns, and need additional fluids urgently to prevent dehydration or kidney failure. Colloid or crystalloid solutions may be used for this purpose. Crystalloids have small molecules, are cheap, easy to use, and provide immediate fluid resuscitation, but may increase oedema. Colloids have larger molecules, cost more, and may provide swifter volume expansion in the intravascular space, but may induce allergic reactions, blood clotting disorders, and kidney failure. This is an update of a Cochrane Review last published in 2013. OBJECTIVES: To assess the effect of using colloids versus crystalloids in critically ill people requiring fluid volume replacement on mortality, need for blood transfusion or renal replacement therapy (RRT), and adverse events (specifically: allergic reactions, itching, rashes). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and two other databases on 23 February 2018. We also searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs of critically ill people who required fluid volume replacement in hospital or emergency out-of-hospital settings. Participants had trauma, burns, or medical conditions such as sepsis. We excluded neonates, elective surgery and caesarean section. We compared a colloid (suspended in any crystalloid solution) versus a crystalloid (isotonic or hypertonic). DATA COLLECTION AND ANALYSIS: Independently, two review authors assessed studies for inclusion, extracted data, assessed risk of bias, and synthesised findings. We assessed the certainty of evidence with GRADE. MAIN RESULTS: We included 69 studies (65 RCTs, 4 quasi-RCTs) with 30,020 participants. Twenty-eight studied starch solutions, 20 dextrans, seven gelatins, and 22 albumin or fresh frozen plasma (FFP); each type of colloid was compared to crystalloids.Participants had a range of conditions typical of critical illness. Ten studies were in out-of-hospital settings. We noted risk of selection bias in some studies, and, as most studies were not prospectively registered, risk of selective outcome reporting. Fourteen studies included participants in the crystalloid group who received or may have received colloids, which might have influenced results.We compared four types of colloid (i.e. starches; dextrans; gelatins; and albumin or FFP) versus crystalloids.Starches versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using starches or crystalloids in mortality at: end of follow-up (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.86 to 1.09; 11,177 participants; 24 studies); within 90 days (RR 1.01, 95% CI 0.90 to 1.14; 10,415 participants; 15 studies); or within 30 days (RR 0.99, 95% CI 0.90 to 1.09; 10,135 participants; 11 studies).We found moderate-certainty evidence that starches probably slightly increase the need for blood transfusion (RR 1.19, 95% CI 1.02 to 1.39; 1917 participants; 8 studies), and RRT (RR 1.30, 95% CI 1.14 to 1.48; 8527 participants; 9 studies). Very low-certainty evidence means we are uncertain whether either fluid affected adverse events: we found little or no difference in allergic reactions (RR 2.59, 95% CI 0.27 to 24.91; 7757 participants; 3 studies), fewer incidences of itching with crystalloids (RR 1.38, 95% CI 1.05 to 1.82; 6946 participants; 2 studies), and fewer incidences of rashes with crystalloids (RR 1.61, 95% CI 0.90 to 2.89; 7007 participants; 2 studies).Dextrans versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using dextrans or crystalloids in mortality at: end of follow-up (RR 0.99, 95% CI 0.88 to 1.11; 4736 participants; 19 studies); or within 90 days or 30 days (RR 0.99, 95% CI 0.87 to 1.12; 3353 participants; 10 studies). We are uncertain whether dextrans or crystalloids reduce the need for blood transfusion, as we found little or no difference in blood transfusions (RR 0.92, 95% CI 0.77 to 1.10; 1272 participants, 3 studies; very low-certainty evidence). We found little or no difference in allergic reactions (RR 6.00, 95% CI 0.25 to 144.93; 739 participants; 4 studies; very low-certainty evidence). No studies measured RRT.Gelatins versus crystalloidsWe found low-certainty evidence that there may be little or no difference between gelatins or crystalloids in mortality: at end of follow-up (RR 0.89, 95% CI 0.74 to 1.08; 1698 participants; 6 studies); within 90 days (RR 0.89, 95% CI 0.73 to 1.09; 1388 participants; 1 study); or within 30 days (RR 0.92, 95% CI 0.74 to 1.16; 1388 participants; 1 study). Evidence for blood transfusion was very low certainty (3 studies), with a low event rate or data not reported by intervention. Data for RRT were not reported separately for gelatins (1 study). We found little or no difference between groups in allergic reactions (very low-certainty evidence).Albumin or FFP versus crystalloidsWe found moderate-certainty evidence that there is probably little or no difference between using albumin or FFP or using crystalloids in mortality at: end of follow-up (RR 0.98, 95% CI 0.92 to 1.06; 13,047 participants; 20 studies); within 90 days (RR 0.98, 95% CI 0.92 to 1.04; 12,492 participants; 10 studies); or within 30 days (RR 0.99, 95% CI 0.93 to 1.06; 12,506 participants; 10 studies). We are uncertain whether either fluid type reduces need for blood transfusion (RR 1.31, 95% CI 0.95 to 1.80; 290 participants; 3 studies; very low-certainty evidence). Using albumin or FFP versus crystalloids may make little or no difference to the need for RRT (RR 1.11, 95% CI 0.96 to 1.27; 3028 participants; 2 studies; very low-certainty evidence), or in allergic reactions (RR 0.75, 95% CI 0.17 to 3.33; 2097 participants, 1 study; very low-certainty evidence). AUTHORS' CONCLUSIONS: Using starches, dextrans, albumin or FFP (moderate-certainty evidence), or gelatins (low-certainty evidence), versus crystalloids probably makes little or no difference to mortality. Starches probably slightly increase the need for blood transfusion and RRT (moderate-certainty evidence), and albumin or FFP may make little or no difference to the need for renal replacement therapy (low-certainty evidence). Evidence for blood transfusions for dextrans, and albumin or FFP, is uncertain. Similarly, evidence for adverse events is uncertain. Certainty of evidence may improve with inclusion of three ongoing studies and seven studies awaiting classification, in future updates.

Synthetic colloid resuscitation in severely injured patients: analysis of a nationwide trauma registry (TraumaRegister DGU).

The purpose of this study was to investigate the efficacy and safety of synthetic colloid resuscitation among severely injured patients. Fluid resuscitation of trauma patients of a nationwide trauma registry was analysed between 2002 and 2015. Effects of synthetic colloid resuscitation in the pre-hospital setting and emergency department on renal failure, renal replacement therapy and multiple organ failure were analysed among patients with ≥2 days intensive care unit stay, and in-hospital mortality was analysed among all patients. 48,484 patients with mean age of 49 years and mean injury severity score of 23 points were included; 72.3% were male and 95.5% had blunt trauma. Risk-adjusted analyses revealed that patients receiving >1,000 ml synthetic colloids experienced an increase of renal failure and renal replacement therapy rates (OR 1.42 and 1.32, respectively, both p ≤ 0.006). Any synthetic colloid use was associated with an increased risk of multiple organ failure (p < 0.001), but there was no effect on hospital mortality (p = 0.594). Between 2002 and 2015 usage of synthetic colloids dropped, likewise did total fluid intake and usage of blood products. The data from this analysis suggests that synthetic colloid resuscitation provides no beneficial effects and might be harmful in patients with severe trauma.

Effects of grass jelly on glycemic control: hydrocolloids may inhibit gut carbohydrase.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate (1) the hydrocolloid properties of grass jelly on reducing glycaemic response, (2) the impact of phenolic compounds in Mesona chinensis L. on glycaemic response. METHODS AND STUDY DESIGN: A total of 15 healthy Chinese men were recruited to this study. On each visit, subjects consumed one of the following three treatments, i.e. glucose solution (T1), grass jelly (Mesona chinensis L.) solution with glucose (T2) or grass jelly gel with glucose (T3). Capillary blood glucose and venous plasma insulin were analysed over a period of 180 min. RESULTS: The incremental area under the curve for capillary glucose and venous plasma insulin for glucose group, grass jelly solution group and grass jelly gel was found to be statistically not significant (p>0.05). In a previous study the co-ingestion of grass jelly with complex carbohydrate was found to reduce glycaemic response. The key difference between the two studies was the use of monosaccharide glucose in the present study, compared to complex carbohydrates in the other. The present study suggests that the glycaemic lowering effect of grass jelly may be dependent on the inhibition of carbohydrase enzymes. CONCLUSIONS: The co-ingestion of Mesona chinensis L. appears to reduce glycaemic response of only complex carbohydrates through the inhibition of carbohydrase. This conclusion was arrived at by the lack of any effect of Mesona chinensis L. on the monosaccharide glucose.

Choice of fluid type: physiological concepts and perioperative indications.

The consensus that i.v. resuscitation fluids should be considered as drugs with specific dose recommendations, contraindications, and side-effects has led to an increased attention for the choice of fluid during perioperative care. In particular, the debate concerning possible adverse effects of unbalanced fluids and hydroxyethyl starches resulted in a re-evaluation of the roles of different fluid types in the perioperative setting. This review provides a concise overview of the current knowledge regarding the efficacy and safety of distinct fluid types for perioperative use. First, basic physiological aspects and possible side-effects are explained. Second, we focus on considerations regarding fluid choice for specific perioperative indications based on an analysis of available randomized controlled trials.

Impact of volume status and volume therapy on the kidney.

Volume resuscitation to correct hypotension in surgical and critically ill patients is a common practice. Available evidence suggests that iatrogenic volume overload is associated with worse outcomes in established acute kidney injury. Intraoperative arterial hypotension is associated with postoperative renal dysfunction, and prompt correction with fluid management protocols that combine inotrope infusions with volume therapy targeted to indices of volume responsiveness should be considered. From the perspective of renal function, the minimum amount of intravenous fluid required to maintain perfusion and oxygen delivery is desirable. Available evidence and expert opinion suggest that balanced crystalloid solutions are preferable to isotonic saline for volume resuscitation. Moreover, albumin has a similar safety profile as crystalloids. Hetastarch-containing colloids have a clear association with acute kidney injury.

Adverse effects of crystalloid and colloid fluids.

Guidelines for infusion fluid therapy rarely take into account that adverse effects occur in a dose-dependent fashion. Adverse effects of crystalloid fluids are related to their preferential distribution to the interstitium of the subcutis, the gut, and the lungs. The gastrointestinal recovery time is prolonged by 2 days when more than 2 litres is administered. Infusion of 6-7 litres during open abdominal surgery results in poor wound healing, pulmonary oedema, and pneumonia. There is also a risk of fatal postoperative pulmonary oedema that might develop several days after the surgery. Even larger amounts cause organ dysfunction by breaking up the interstitial matrix and allowing the formation of lacunae of fluid in the skin and central organs, such as the heart. Adverse effects of colloid fluids include anaphylactic reactions, which occur in 1 out of 500 infusions. The possibility that hydroxyethyl starch causes kidney injury in patients other than those with sepsis is still unclear. For both crystalloid and colloid fluids, coagulation becomes impaired when the induced haemodilution has reached 40%. Coagulopathy is aggravated by co-existing hypothermia. Although oedema can occur from both crystalloid and colloid fluids, these differ in pathophysiology. To balance fluid-induced adverse effects, this review suggests that a colloid fluid is indicated when the infused crystalloid volume exceeds 3-4 litres, plasma volume support is still needed, and the transfusion of blood products is not yet indicated.

Cell-compatible conducting polyaniline films prepared in colloidal dispersion mode.

Conducting polyaniline can be prepared and modified using several procedures, all of which can significantly influence its applicability in different fields of biomedicine or biotechnology. The modifications of surface properties are crucial with respect to the possible applications of this polymer in tissue engineering or as biosensors. Innovative technique for preparing polyaniline films via in-situ polymerization in colloidal dispersion mode using four stabilizers (poly-N-vinylpyrrolidone; sodium dodecylsulfate; Tween 20 and Pluronic F108) was developed. The surface energy, conductivity, spectroscopic features, and cell compatibility of thin polyaniline films were determined using contact-angle measurement, the van der Pauw method, Fourier-transform infrared spectroscopy, and assay conducted on mouse fibroblasts, respectively. The stabilizers significantly influenced not only the surface and electrical properties of the films but also their cell compatibility. Sodium dodecylsulfate seems preferentially to combine both the high conductivity and good cell compatibility. Moreover, the films with sodium dodecylsulfate were non-irritant for skin, which was confirmed by their in-vitro exposure to the 3D-reconstructed human tissue model.

Perioperative Fluid Therapy.

Anesthesia can lead to pathophysiologic changes that dramatically alter the fluid balance of the body compartments and the intravascular space. Fluid administration can be monitored and evaluated using static and dynamic indexes. Guidelines for fluid rates during anesthesia begin with 3 mL/kg/h in cats and 5 mL/kg/h in dogs. If at all possible, patients should be stabilized and electrolyte disturbances should be corrected before general anesthesia.

Topical and cutaneous delivery using nanosystems.

The goal of topical and cutaneous delivery is to deliver therapeutic and other substances to a desired target site in the skin at appropriate doses to achieve a safe and efficacious outcome. Normally, however, when the stratum corneum is intact and the skin barrier is uncompromised, this is limited to molecules that are relatively lipophilic, small and uncharged, thereby excluding many potentially useful therapeutic peptides, proteins, vaccines, gene fragments or drug-carrying particles. In this review we will describe how nanosystems are being increasingly exploited for topical and cutaneous delivery, particularly for these previously difficult substances. This is also being driven by the development of novel technologies, which include minimally invasive delivery systems and more precise fabrication techniques. While there is a vast array of nanosystems under development and many undergoing advanced clinical trials, relatively few have achieved full translation to clinical practice. This slow uptake may be due, in part, to the need for a rigorous demonstration of safety in these new nanotechnologies. Some of the safety aspects associated with nanosystems will be considered in this review.

Evidence-based fluid management in the ICU.

PURPOSE OF REVIEW: Evidence-based fluid therapy is complicated by blurred boundaries toward other fields of therapy and the majority of trials not focusing on patient-relevant outcomes. Additionally, recent trials unsettled the faith in traditional concepts on fluid therapy. The article reviews the evidence on diagnosis and treatment of hypovolemia and discusses the use of balanced solutions and early goal-directed therapy (EGDT) in septic shock resuscitation. RECENT FINDINGS: Hypovolemia should be diagnosed and its treatment guided by a multifaceted approach, including medical history, physical examination, volume responsiveness, and technical parameters - dynamic indicators, volumetric indicators, sonography, and metabolic indicators. Central venous pressure and pulmonary artery occlusion pressure should be avoided. In ICU patients, balanced crystalloids should primarily be used, because unbalanced infusions (especially saline) cause hyperchloremic acidosis which is associated with renal impairment and infections. Colloids are beneficial to restore blood volume rapidly. Hydroxyethyl starch may be harmful although the validity of the respective recent studies is limited by methodological flaws. Early aggressive fluid therapy is still beneficial in septic shock resuscitation, despite recent trials challenging the EGDT concept. Today, 10 years after Rivers, 'usual care' includes aggressive fluid resuscitation that is as effective as formal EGDT. SUMMARY: Evidence-based fluid therapy includes a multifaceted diagnostic approach, the primary use of balanced crystalloids and early aggressive (septic) shock resuscitation.