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.

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.

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.

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.

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.

Intravenous solutions in the care of patients with volume depletion and electrolyte abnormalities.

Infusion fluids are often given to restore blood pressure (volume resuscitation), but may also be administered to replace ongoing losses, match insensible losses, correct electrolyte or acid-base disorders, or provide glucose. The development of new infusion fluids has provided clinicians with a wide range of products. Although the choice for a certain infusion fluid is often driven more by habit than by careful consideration, we believe it is useful to approach infusion fluids as drugs and consider their pharmacokinetic and pharmacodynamic characteristics. This approach not only explains why infusion fluids may cause electrolyte and acid-base disturbances, but also why they may compromise kidney function or coagulation. In this teaching case, we present a 19-year-old patient in whom severe hypernatremia developed as a result of normal saline solution infusion and explore the pharmacokinetic and pharmacodynamic effects of frequently used infusion fluids. We review clinical evidence to guide the selection of the optimal infusion fluid.

Which intravenous fluid for the surgical patient?

PURPOSE OF REVIEW: This review appraises recent evidence and provides clinical guidance on optimal perioperative fluid therapy. RECENT FINDINGS: Choice of perioperative intravenous fluid continues to be the source of much debate. Not all crystalloids are equivalent, and there is growing evidence that balanced solutions are superior to 0.9% saline in many situations. Recent evidence from the critical care population has highlighted risks associated with synthetic colloids; this and the absence of demonstrable benefit in the surgical population make it difficult to recommend their use in the perioperative period. Giving the correct amount of fluid may be as important as the choice of the fluid used. There is increasing evidence that excessive positive fluid balance is harmful to patients but there have been no randomized trials comparing maintenance fluid strategy. A knowledge of the physiology and accurate estimation of fluid balance is important for water and electrolyte homeostasis until the patient is able to resume adequate enteral nutrition. SUMMARY: Balanced crystalloids are the fluid of choice for perioperative resuscitation and optimization in patients not requiring blood products. Avoidance of a grossly positive sodium and water balance during the maintenance phase is likely to be important, but has not been assessed in randomized trials.

Intravenous fluids: should we go with the flow?

Sensitive monitoring should be used when prescribing intravenous fluids for volume resuscitation. The extent and duration of tissue hypoperfusion determine the severity of cellular damage, which should be kept to a minimum with timely volume substitution. Optimizing the filling status to normovolaemia may boost the resuscitation success. Macrocirculatory pressure values are not sensitive in this indication. While the Surviving Sepsis Campaign guidelines focus on these conventional pressure parameters, the guidelines from the European Society of Anaesthesiology (ESA) on perioperative bleeding management recommend individualized care by monitoring the actual volume status and correcting hypovolaemia promptly if present. The motto is: 'give what is missing'. The credo of the ESA guidelines is to use management algorithms with predefined intervention triggers. Stop signals should help in avoiding hyper-resuscitation. The high-quality evidence-based S3 guidelines on volume therapy in adults have recently been prepared by 14 German scientific societies. Statements include, for example, repeated clinical inspection including turgor of the skin and mucosa. Adjunctive laboratory parameters such as central venous oxygen saturation, lactate, base excess and haematocrit should be considered. The S3 guidelines propose the use of flow-based and/or dynamic preload parameters for guiding volume therapy. Fluid challenges and/or the leg-raising test (autotransfusion) should be performed. The statement from the Co-ordination group for Mutual Recognition and Decentralized Procedures-Human informs healthcare professionals to consider applying individualized medicine and using sensitive monitoring to assess hypovolaemia. The authorities encourage a personalized goal-directed volume resuscitation technique.

Parenteral fluid regimens for improving functional outcome in people with acute stroke.

BACKGROUND: Parenteral fluids are commonly used in people with acute stroke with poor oral fluid intake. However, the balance between benefit and harm for different fluid regimens is unclear. OBJECTIVES: To assess whether different parenteral fluid regimens lead to differences in death, or death or dependence, after stroke based on fluid type, fluid volume, duration of fluid administration, and mode of delivery. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2015), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE) (Cochrane Library 2015, Issue 5), MEDLINE (2008 to May 2015), EMBASE (2008 to May 2015), and CINAHL (1982 to May 2015). We also searched ongoing trials registers (May 2015) and reference lists, performed cited reference searches, and contacted authors. SELECTION CRITERIA: Randomised trials of parenteral fluid regimens in adults with ischaemic or haemorrhagic stroke within seven days of stroke onset that reported death or dependence. DATA COLLECTION AND ANALYSIS: One review author screened titles and abstracts. We obtained the full-text articles of relevant studies, and two review authors independently selected trials for inclusion and extracted data. We used Cochrane's tool for bias assessment. MAIN RESULTS: We included 12 studies (2351 participants: range 27 to 841).Characteristics: The 12 included studies compared hypertonic (colloids) with isotonic fluids (crystalloids); of these, five studies (1420 participants) also compared 0.9% saline with another fluid. No data were available to make other comparisons. Delay from stroke to recruitment varied from less than 24 hours to 72 hours. Duration of fluid delivery was between two hours and 10 days.Bias assessment: Investigators and participants in eight of the 12 included studies were blind to treatment allocation, seven of the 12 included studies gave details of randomisation, and eight of the 12 included studies reported all outcomes measured. RESULTS: There were no relevant completed trials that addressed the effect of volume, duration, or mode of fluid delivery on death or dependence in people with stroke.The odds of death or dependence were similar in participants allocated to colloids or crystalloid fluid regimens (odds ratio (OR) 0.97, 95% confidence interval (CI) 0.79 to 1.21, five studies, I² = 58%, low-quality evidence), and between 0.9% saline or other fluid regimens (OR 1.04, 95% CI 0.82 to 1.32, three studies, I² = 71%, low-quality evidence). There was substantial heterogeneity in these estimates.The odds of death were similar between colloids and crystalloids (OR 1.02, 95% CI 0.82 to 1.27, 12 studies, I² = 24%, moderate-quality evidence), and 0.9% saline and other fluids (OR 0.87, 95% CI 0.67 to 1.12, five studies, I² = 53%, low-quality evidence). The odds of pulmonary oedema were higher in participants allocated to colloids (OR 2.34, 95% CI 1.28 to 4.29, I² = 0%). Although the studies observed a higher risk of cerebral oedema (OR 0.20, 95% CI 0.02 to 1.74) and pneumonia (OR 0.58, 95% CI 0.17 to 2.01) with crystalloids, we could not exclude clinically important benefits or harms. AUTHORS' CONCLUSIONS: We found no evidence that colloids were associated with lower odds of death or dependence in the medium term after stroke compared with crystalloids, though colloids were associated with greater odds of pulmonary oedema. We found no evidence to guide the best volume, duration, or mode of parenteral fluid delivery for people with acute stroke.

CRYSTALLOID PRELOAD SHOWS TRANSIENT SUPERIORITY OVER COLLOID, OR THEIR COMBINATION IN SPINAL ANAESTHESIA-INDUCED HYPOTENSION PROPHYLAXIS FOR CAESAREAN SECTION.

BACKGROUND: Many studies comparing different intravenous fluid types usually do not use equipotent volumes of 3:1 crystalloid: colloid ratio in such comparisons. Conflicting results emanate from such studies. This study was designed to compare the efficacy of equipotent volumes of crystalloid, colloid and combination of crystalloid/colloid in spinal anaesthesia-induced hypotension prophylaxis. METHODOLOGY: Pregnant women scheduled for elective Caesarean section were prospectively randomized to three groups to each received either 1 500 ml of Ringers lactate, or 500 ml of 6% pentastarch or a combination of 250 ml of 6% pentastarch and 750 ml of Ringers lactate intravenous fluid preload, before spinal anaesthesia. Hemodynamic variables were monitored. RESULTS: First 10 minutes, crystalloid showed better efficacy in hypotension prophylaxis over the other regimen. In the next 30 minutes however, there were no significant differences between the groups. CONCLUSION: Crystalloids proved more effective than colloid or their combination in hypotension prophylaxis in the first 10 minutes after spinal anaesthesia.

Crystalloids and colloids in critical patient resuscitation.

Fluid resuscitation is essential for the survival of critically ill patients in shock, regardless of the origin of shock. A number of crystalloids and colloids (synthetic and natural) are currently available, and there is strong controversy regarding which type of fluid should be administered and the potential adverse effects associated with the use of these products, especially the development of renal failure requiring renal replacement therapy. Recently, several clinical trials and metaanalyses have suggested the use of hydroxyethyl starch (130/0.4) to be associated with an increased risk of death and kidney failure, and data have been obtained showing clinical benefit with the use of crystalloids that contain a lesser concentration of sodium and chlorine than normal saline. This new information has increased uncertainty among clinicians regarding which type of fluid should be used. We therefore have conducted a review of the literature with a view to developing practical recommendations on the use of fluids in the resuscitation phase in critically ill adults.

Nanoparticle-mediated pulmonary drug delivery: a review.

Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API) forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed.

Fluid management in acute respiratory distress syndrome.

PURPOSE OF REVIEW: Fluid management is one of the most important measures shown to impact acute respiratory distress syndrome (ARDS) outcomes. This review summarizes the current strategies aimed at evaluating and modulating lung fluid balance. RECENT FINDINGS: Multiple recent studies have shown that a conservative fluid management in ARDS patients had beneficial effects on morbidity and mortality. These findings were replicated also in different patient populations assumed to have potential deleterious effects from this approach. So far, only one retrospective study raised the possibility of impaired cognitive function in ARDS patients managed with a conservative fluid strategy. Thermodilution methods and serum biomarkers can be used to monitor lung fluid balance and guide therapy. Recent evidence has indicated significant detrimental effects associated with beta-2 agonists use in ARDS, despite a putative beneficial role in the resolution of alveolar edema seen in preliminary studies. SUMMARY: Dynamic monitoring of lung fluid balance needs to be implemented to guide fluid therapy in ARDS patients. A conservative fluid strategy seems safe and yields overall good clinical outcomes, but its impact on cognitive function needs to be evaluated in further studies. The role of colloids and other pharmacological agents deserves further investigation.

Colloid solutions for fluid resuscitation in patients with sepsis: systematic review of randomized controlled trials.

BACKGROUND: Colloids are widely used for fluid resuscitation in patients with sepsis. But the optimal type of fluid remains unclear. OBJECTIVE: Our aim was to assess the effects on mortality and safety of different colloid solutions in patients with sepsis requiring volume replacement by examining direct comparisons of colloid solutions. METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, China Biological Medicine Database, VIP Chinese Journals Database, and CNKI China National Knowledge Infrastructure Whole Article Database. Randomized clinical trials comparing different colloids in septic patients needing fluid resuscitation were selected. RESULTS: Seventeen randomized clinical trials with a total 1281 participants met the inclusion criteria. Mortality was obtained in all trials. For intervention of albumin vs. hydroxyethyl starch solution (HES), the relative risk (RR) of death was 0.98 (95% confidence interval [CI] 0.74-1.30). For intervention of albumin vs. gelatin, the RR of death was 2.4 (95% CI 0.31-18.35). For intervention of gelatin vs. HES, the RR of death was 1.02 (95% CI 0.79-1.32). For the intervention of HES vs. dextran, the RR of death was 1.38 (95% CI 0.28-6.78). For the intervention of gelatin vs. dextran, RR of death was not estimable. For albumin vs. dextran, no trial was included. Four trials of intervention of albumin vs. HES recorded the change of severity score. CONCLUSIONS: There is no evidence that one colloid solution is more effective and safer than another for fluid resuscitation in sepsis. The severity score is improved in HES, but the confidence intervals are wide.

Colloid solutions for fluid resuscitation.

BACKGROUND: Colloids are widely used in the replacement of fluid volume. However doubts remain as to which colloid is best. Different colloids vary in their molecular weight and therefore in the length of time they remain in the circulatory system. Because of this and their other characteristics, they may differ in their safety and efficacy. OBJECTIVES: To compare the effects of different colloid solutions in patients thought to need volume replacement. SEARCH METHODS: We searched the Cochrane Injuries Specialised Register (searched 1 Dec 2011), Cochrane Central Register of Controlled Trials 2011, issue 4 (The Cochrane Library); MEDLINE (Ovid) (1948 to November Week 3 2011); EMBASE (Ovid) (1974 to 2011 Week 47); ISI Web of Science: Science Citation Index Expanded (1970 to 1 Dec 2011); ISI Web of Science: Conference Proceedings Citation Index-Science (1990 to 1 Dec 2011); CINAHL (EBSCO) (1982 to 1 Dec 2011); National Research Register (2007, Issue 1) and PubMed (searched 1 Dec 2011). Bibliographies of trials retrieved were searched, and for the initial version of the review drug companies manufacturing colloids were contacted for information (1999). SELECTION CRITERIA: Randomised controlled trials comparing colloid solutions in critically ill and surgical patients thought to need volume replacement. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data and assessed the quality of the trials. The outcomes sought were death, amount of whole blood transfused, and incidence of adverse reactions. MAIN RESULTS: Ninety trials, with a total of 5678 participants, met the inclusion criteria. Quality of allocation concealment was judged to be adequate in 35 trials and poor or uncertain in the rest.Deaths were obtained in 61 trials. For albumin or PPF versus hydroxyethyl starch (HES) 32 trials (n = 1769) reported mortality. The pooled relative risk (RR) was 1.07 (95% CI 0.87 to 1.32). When the trials by Boldt were removed from the analysis the pooled RR was 0.90 (95% CI 0.68 to 1.20). For albumin or PPF versus gelatin, nine trials (n = 824) reported mortality. The RR was 0.89 (95% CI 0.65 to 1.21). Removing the study by Boldt from the analysis did not change the RR or confidence intervals. For albumin or PPF versus Dextran four trials (n = 360) reported mortality. The RR was 3.75 (95% CI 0.42 to 33.09). For gelatin versus HES 25 trials (n = 1756) reported mortality and the RR was 1.03 (95% CI 0.84 to 1.26). When the trials by Boldt were removed from the analysis the pooled RR was 1.04 (95% CI 0.85 to 1.27). RR was not estimable in the gelatin versus dextran and HES versus dextran groups.Forty five trials recorded the amount of blood transfused, however quantitative analysis was not possible due to skewness and variable reporting. Twenty-four trials recorded adverse reactions, with two studies reporting possible adverse reactions to Gel and one to HES. AUTHORS' CONCLUSIONS: From this review, there is no evidence that one colloid solution is more effective or safe than any other, although the confidence intervals are wide and do not exclude clinically significant differences between colloids. Larger trials of fluid therapy are needed if clinically significant differences in mortality are to be detected or excluded.

Fluid resuscitation in patients with traumatic brain injury: what is a SAFE approach?

PURPOSE OF REVIEW: In patients with traumatic brain injury (TBI), dysfunction of the neurovascular unit ('blood-brain barrier') is a common finding, resulting in maldistribution of water and osmoles within the brain. The purpose of the present article is to review the underlying physiology of osmolality and fluid therapy in TBI. RECENT FINDINGS: The findings of the 'Saline versus Albumin Fluid Evaluation' study suggest that infusion of colloidal solutions is associated with adverse outcomes as compared with sole crystalloid infusion in patients suffering from TBI. Comparison of calculated osmolarity and measured in-vitro osmolality suggests that human albumin solutions, Hartmann's solution, and, to a lesser extent, gelatine preparations are hypo-osmolar, and may, therefore, increase brain volume and intracranial pressure. SUMMARY: In the context of the published literature on this topic, it appears that the osmolality of an infusion solution rather than the colloid osmotic pressure per se represents the key determinant in the pathogenesis of cerebral edema formation.

[Morphological changes of the intestine in experimental acute intestinal infection in the treatment of colloidal silver].

At the present stage of infectionist practice in the treatment of acute intestinal infections caused by opportunistic microorganisms, colloidal silver is used with a particle size of 25 nm as an alternative to conventional causal therapy. In 32 rats, distributed in 4 groups of 8 animals each (intact; healthy, got colloidal silver; with a modeled acute intestinal infection in the basic treatment and with the addition of colloidal silver), histological examination was performed of small and large intestine of rats. Oral administration of colloidal silver at a dose of 0.02 mg/day to intact rats did not lead to changes in morphometric parameters compared to the norm, and during early convalescence in rats with acute intestinal infections were observed destructive and compensatory changes in the intestine, which depended on the treatment regimen. With the introduction of colloidal silver decreased activity of the inflammatory process and the severity of morphological changes in tissues of small and large intestine, indicating that the positive effect of study drug compared with baseline therapy.

The efficacy and safety of colloid resuscitation in the critically ill.

Despite evidence from clinical studies and meta-analyses that resuscitation with colloids or crystalloids is equally effective in critically ill patients, and despite reports from high-quality clinical trials and meta-analyses regarding nephrotoxic effects, increased risk of bleeding, and a trend toward higher mortality in these patients after the use of hydroxyethyl starch (HES) solutions, colloids remain popular and the use of HES solutions is increasing worldwide. We investigated the major rationales for colloid use, namely that colloids are more effective plasma expanders than crystalloids, that synthetic colloids are as safe as albumin, that HES solutions have the best risk/benefit profile among the synthetic colloids, and that the third-generation HES 130/0.4 has fewer adverse effects than older starches. Evidence from clinical studies shows that comparable resuscitation is achieved with considerably less crystalloid volumes than frequently suggested, namely, <2-fold the volume of colloids. Albumin is safe in intensive care unit patients except in patients with closed head injury. All synthetic colloids, namely, dextran, gelatin, and HES have dose-related side effects, which are coagulopathy, renal failure, and tissue storage. In patients with severe sepsis, higher doses of HES may be associated with excess mortality. The assumption that third-generation HES 130/0.4 has fewer adverse effects is yet unproven. Clinical trials on HES 130/0.4 have notable shortcomings. Mostly, they were not performed in intensive care unit or emergency department patients, had short observation periods of 24 to 48 hours, used cumulative doses below 1 daily dose limit (50 mL/kg), and used unsuitable control fluids such as other HES solutions or gelatins. In conclusion, the preferred use of colloidal solutions for resuscitation of patients with acute hypovolemia is based on rationales that are not supported by clinical evidence. Synthetic colloids are not superior in critically ill adults and children but must be considered harmful depending on the cumulative dose administered. Safe threshold doses need to be determined in studies in high-risk patients and observation periods of 90 days. Such studies on HES 130/0.4 are still lacking despite its widespread and increasing use. Because there are safer and equally effective alternatives in the form of crystalloids, use of synthetic colloids should be avoided except in the context of clinical studies.