Hydroxyethyl Starch for Fluid Management in Patients Undergoing Major Abdominal Surgery: A Systematic Review With Meta-analysis and Trial Sequential Analysis.

BACKGROUND: In critically ill patients, warnings about a risk of death and acute kidney injury (AKI) with hydroxyethyl starch (HES) solutions have been raised. However, HES solutions may yet have a role to play in major abdominal surgery. This meta-analysis and trial sequential analysis (TSA) aimed to investigate the effect of HES intravascular volume replacement on the risk of AKI, intraoperative blood transfusion, and postoperative intra-abdominal complications compared to crystalloid intravascular volume replacement. METHODS: In this meta-analysis and TSA, we searched for randomized controlled trials (RCTs) comparing intraoperative HES intravascular volume replacement to crystalloid intravascular volume replacement in adult patients undergoing major abdominal surgery. Primary outcome was 30-day AKI, defined as a binary outcome according to Kidney Disease Improving Global Outcomes (KDIGO) criteria, combining stages 1, 2, and 3 into an AKI category versus no AKI category (stage 0). Secondary outcomes included rates of intraoperative blood transfusion and postoperative intra-abdominal complications. We used random effects models to calculate summary estimates. We used relative risk (RR) as summary measure for dichotomous outcomes, with corresponding 95% confidence intervals (CIs) for the primary outcome (P value <.05 was considered statistically significant) and 99% CI after Bonferroni correction for the secondary outcomes (P value <.01 was considered statistically significant). RESULTS: Seven RCTs including 2398 patients were included. HES intravascular volume replacement was not associated with an increased risk of 30-day AKI (RR = 1.22, 95% CI, 0.94-1.59; P = .13), when compared to crystalloid intravascular volume replacement. According to TSA, this analysis was underpowered. HES intravascular volume replacement was associated with higher rates of blood transfusion (RR = 1.57 99% CI, 1.10-2.25; P = .001), and similar rates of postoperative intra-abdominal complications (RR = 0.76 99% CI, 0.57-1.02; P = .02). CONCLUSIONS: In this meta-analysis to focus on HES intravascular volume replacement in major abdominal surgery, HES intravascular volume replacement was not associated with a higher risk of 30-day AKI when compared to crystalloid intravascular volume replacement. However, CI and TSA do not exclude harmful effects of HES intravascular volume replacement on the renal function.

Modified fluid gelatin 4% for perioperative volume replacement in pediatric patients (GPS): Results of a European prospective noninterventional multicenter study.

INTRODUCTION: Modified fluid gelatin 4% is approved for use in children, but there is still a surprising lack of clinical studies including large numbers of pediatric patients. Therefore, we performed a European prospective noninterventional multicenter study to evaluate the use of a modified fluid gelatin 4% in saline (sal-GEL) or an acetate-containing balanced electrolyte solution (bal-GEL) in children undergoing major pediatric surgery. AIMS: The primary aim was to assess the indications and dosing of modified fluid gelatin, and the secondary aim was to assess the safety and efficacy, focusing, in particular, on routinely collected clinical parameters. METHODS: Children aged up to 12 years with ASA risk scores of I-III receiving sal-GEL or bal-GEL were followed perioperatively. Demographic data, surgical procedures performed, anesthesia, hemodynamic and laboratory data, adverse events, and adverse drug reactions were documented using a standardized case report form. RESULTS: 601 children that were investigated at 13 European pediatric centers from May 2015 to March 2020 (sal-GEL 20.1%, bal-GEL 79.9%; mean age 29.1 ± 38.6 (range 0-144) months; body weight 12.1 ± 10.5 (1.4-70) kg) were included in the analysis. The most frequent indications for GEL infusion were hemodynamic instability without bleeding (76.0%), crystalloids alone not being sufficient for hemodynamic stabilization (55.7%), replacement of preoperative deficit (26.0%), and significant bleeding (13.0%). Mean infused GEL volume was 13.0 ± 5.3 (2.4-37.5) ml kg-1 . The total dose was affected by age, with higher doses in younger patients. After gelatin infusion, mean arterial pressure increased (mean change 8.5 ± 7.3 [95% CI: 8 to 9.1] mmHg), and the hemoglobin concentrations decreased significantly (mean change -1.1 ± 1.8 [95% CI: -1.2 to -0.9] g·dL-1 ). Acid-base parameters were more stable with bal-GEL. No serious adverse drug reactions directly related to gelatin (i.e., anaphylactoid reaction, clotting disorders, and renal failure) were observed. CONCLUSION: Moderate doses up to 20 ml kg-1 of modified fluid gelatin were infused most frequently to improve hemodynamic stability in children undergoing major pediatric surgery. The acid-base balance was more stable when gelatin in a balanced electrolyte solution was used instead of saline. No serious adverse drug reactions associated with gelatin were observed.

Intraoperative Intravascular Effect of Lactated Ringer's Solution and Hyperoncotic Albumin During Hemorrhage in Cystectomy Patients.

BACKGROUND: The intraoperative effect of 20% albumin on plasma volume during surgery involving major blood loss has not been explored extensively due to methodological difficulties. Crystalloids poorly expand the plasma volume, and using a colloid might then be a way to avoid fluid overload. As doubts have been raised about synthetic colloids, albumin solutions are currently used more extensively. This study presents a methodological development showing how plasma volume expansion can be studied in surgical settings with the coinfusion of 20% albumin and lactated Ringer's solution. METHODS: In this single-arm, single-center feasibility study, an intravenous (i.v.) infusion of 3 mL·kg·BW-1 of 20% albumin was administered over 30 minutes to 23 cystectomy patients during the bleeding phase in addition to lactated Ringer's solution to correct blood loss. Blood samples were measured at regular intervals over a period of 300 minutes to estimate the blood volume expansion resulting from simultaneous infusions of lactated Ringer's and 20% albumin solutions, using a regression equation and the area under the volume-time curve method. RESULTS: Mean hemorrhage was 974 mL (standard deviation [SD] ± 381). The regression method showed strong correlation (r2 = 0.58) between blood loss minus blood volume expansion and the independent effects of the infused volume of lactated Ringer's and 20% albumin solutions. The mean plasma volume expansion attributable to the infusion of lactated Ringer's solution amounted to 0.38 (95% confidence interval [CI], 0.31-0.49) of the infused volume; for the 20% albumin, it was 1.94 mL/mL (95% CI, 1.41-2.46 mL/mL) over 5 hours on average (regression method). The mean within-patient change was 0.20 mL/mL (± 0.06 mL/mL) for the lactated Ringer's solution and 2.20 mL/mL (±1.31 mL/mL) for the 20% albumin using the area under the volume-time curve method. CONCLUSIONS: Blood volume expansion averaged 1.9-2.2 times the infused volume of 20% albumin during surgery associated with hemorrhage of around 1000 mL. This effect was long standing and approximately 5 times stronger than for the lactated Ringer's solution. Twenty percent albumin boosts the plasma volume expansion of lactated Ringer's solution to as high as 40% of the infused volume on the average, which is an effect that lasts at least 5 hours.

Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass induces a profound inflammatory response that, when severe, can lead to multiorgan system dysfunction. Preliminary data suggest that administration of hydroxyethyl starch (HES) solutions may mitigate an inflammatory response and improve pulmonary function. Our goal was to examine the effect of 6% HES 130/0.4 versus 5% human albumin given for intravascular plasma volume replacement on the perioperative inflammatory response and pulmonary function in patients undergoing cardiac surgery. METHODS: This was a subinvestigation of a blinded, parallel-group, randomized clinical trial of patients undergoing elective aortic valve replacement surgery at the Cleveland Clinic main campus, titled "Effect of 6% Hydroxyethyl Starch 130/0.4 on Kidney and Haemostatic Function in Cardiac Surgical Patients." Of 141 patients who were randomized to receive either 6% HES 130/0.4 or 5% human albumin for intraoperative plasma volume replacement, 135 patients were included in the data analysis (HES n = 66, albumin n = 69). We assessed the cardiopulmonary bypass-induced inflammatory response end points by comparing the 2 groups' serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF), measured at baseline and at 1 and 24 hours after surgery. We also compared the 2 groups' postoperative pulmonary function end points, including the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2 ratio), dynamic lung compliance, oxygenation index (OI), and ventilation index (VI) at baseline, within 1 hour of arrival to the intensive care unit, and before tracheal extubation. The differences in the postoperative levels of inflammatory response and pulmonary function between the HES and albumin groups were assessed individually in linear mixed models. RESULTS: Serum concentrations of the inflammatory markers (TNF-α, IL-6, MIF) were not significantly different (P ≥ .05) between patients who received 6% HES 130/0.4 or 5% albumin, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). The results of pulmonary function parameters (Pao2:Fio2 ratio, dynamic compliance, OI, VI) were not significantly different (P ≥ .05) between groups, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). CONCLUSIONS: Our investigation found no significant difference in the concentrations of inflammatory markers and measures of pulmonary function between cardiac surgical patients who received 6% HES 130/0.4 versus 5% albumin.

Clinical Outcomes and Medical Costs of Hydration Therapy with Hydroxyethyl Starch (130/0.4) or Acute Single Infarction.

OBJECTIVES: To investigate the effects of hydration with or without Hydroxyethyl Starch (HES) 130/0.4 on neurological outcomes and medical costs during hospitalisation in patients with a single infarction (SI) in the posterior lenticulostriate artery (LSA) territory. MATERIALS AND METHODS: In this retrospective, single-centre, non-blinded cohort study, SI in the posterior LSA was defined as an ischaemic lesion with a high-signal intensity area ≥20 mm. All patients received basic stroke care within 48 h of symptom onset between April 2015 and January 2019. Patients were divided into the following two groups by clinician's preference: 1) those administered HES 130/0.4 and 2) those receiving other infusion fluid. The relationships between hospital costs and hydration therapy type were examined. RESULTS: Eighteen (31%) of 58 patients received HES 130/0.4. The HES group had a significantly lower total cost than the control group (3.6 vs. 6.4 million yen, p=0.006). Moreover, the HES group had a significantly shorter hospital stay duration (79.5 vs. 141.0 days) and lower National Institutes of Health Stroke Scale score on day 7. Multivariate analysis found that HES 130/0.4 administration was an independent factor associated with high costs. CONCLUSIONS: Hydration therapy with HES 130/0.4 significantly decreased the total costs and hospitalisation duration of patients with SI in the posterior LSA territory.

Hydroxyethyl Starch 6% 130/0.4 in a Balanced Electrolyte Solution and Renal Function After Nephrectomy.

BACKGROUND: Although previous studies have reported nephrotoxicity associated with hydroxyethyl starch (HES), the long-term effect of HES on renal function after nephrectomy has rarely been reported. We evaluated the association between intraoperative HES administration and short- and long-term renal function after nephrectomy. METHODS: We retrospectively reviewed 1106 patients who underwent partial or radical nephrectomy. The patients were divided into 2 groups: patients who received (HES group) or did not receive 6% HES 130/0.4 intraoperatively (non-HES group). The primary outcome was new-onset chronic kidney disease (CKD) stage 3a (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m) or higher or all-cause mortality during 60 months after surgery. Propensity score matching was performed to address baseline differences between the 2 groups. Renal survival determined by stage 3a and stage 5 CKD (eGFR <15 mL/min/1.73 m) or all-cause mortality were compared up to 60 months before and after matching. We compared postoperative acute kidney injury (AKI) and CKD upstaging in the matched cohort as secondary outcomes. Ordinal logistic regression and Cox proportional hazards regression analyses using inverse probability of treatment weighting were performed for postoperative AKI and our primary outcome, respectively. A subgroup analysis of partial nephrectomy was performed. RESULTS: Thirty percent of patients received HES intraoperatively. Balanced solution and 0.9% normal saline was administered during surgery in both groups. Renal survival was not significantly different between groups after matching (log-rank test P = .377 for our primary outcome, and P = .981 for stage 5 or all-cause mortality, respectively). In the matched cohort (HES group: n = 280, non-HES group: n = 280), the incidence of AKI or CKD upstaging at 1 year was not significantly different (AKI: n = 94, 33.6% in HES group versus n = 90, 32.1% in non-HES group; CKD upstaging: n = 132, 47.1% in HES group versus n = 122, 43.6% in non-HES group; odds ratio [OR], 1.16; 95% confidence interval [CI], 0.83-1.61; P = .396). Intraoperative HES administration was not associated with postoperative renal outcomes (AKI: OR, 0.97; 95% CI, 0.81-1.16; P = .723; CKD stage 3a or higher or all-cause mortality: hazard ratio, 1.01; 95% CI, 0.89-1.14; P = .920). Subgroup analysis yielded similar results. CONCLUSIONS: Intraoperative 6% HES 130/0.4 administration was not significantly associated with short- and long-term renal function or renal survival up to 5 years in patients undergoing partial or radical nephrectomy. However, wide CI including large harm effect precludes firm conclusion and inadequate assessment of safety cannot be ruled out by our results.

Postoperative renal morbidity and mortality after volume replacement with hydroxyethyl starch 130/0.4 or albumin during surgery: a propensity score-matched study.

PURPOSE: We aimed to compare retrospectively the rates of renal morbidity and mortality in surgical patients receiving 6% HES 130/0.4 to those receiving albumin. METHODS: From a Japanese nationwide medical database between 2014 and 2016, we identified adults who received HES 130/0.4 (HES group) or albumin (albumin group) as a single colloid solution on the day of surgery. After propensity score matching, the two groups were analyzed with χ2 or Mann Whitney U test. The primary outcome was the incidence of acute kidney injury (AKI). Secondary outcomes included the incidence of renal-replacement therapy, hospital length of stay, in-hospital 30-day mortality, the use of vasoactive agents, and the fluid requirement on the day of surgery. RESULTS: Of 76,048 patients in the database, propensity score matching identified 289 matched pairs. There was no statistically significant difference in the incidence of AKI between the HES and the albumin group (15.2% vs. 20.8%, respectively: P = 0.08). The secondary outcomes did not differ between groups except the following. Median hospital stay was 5 days shorter in the HES group (18 vs. 23 days; P < 0.001), and the median net fluid requirement on the day of surgery was 15 mL/kg lower in the HES group (140 vs. 155 mL/kg, respectively; P = 0.01). CONCLUSIONS: Postoperative renal morbidity and mortality did not differ between patients receiving HES 130/0.4 and those receiving albumin. HES 130/0.4 was associated with shorter hospital stay and less fluid requirement compared to albumin. These findings support the use of 6% HES 130/0.4 for perioperative volume replacement as an alternative to albumin. TRIAL REGISTRATION: UMIN000027896 and the date of registration was June 30, 2017 at https://www.umin.ac.jp/ctr/index-j.html .

Fluid volume kinetics of 20% albumin.

AIMS: A population kinetic model was developed for the body fluid shifts occurring when 20% albumin is given by intravenous infusion. The aim was to study whether its efficacy to expand the plasma volume is impaired after major surgery. METHODS: An intravenous infusion of 3 mL/kg 20% albumin over 30 minutes was given to 15 volunteers and to 15 patients on the 1st day after major open abdominal surgery. Blood samples and urine were collected during 5 hours. Mixed-effect modelling software was used to develop a fluid volume kinetic model, using blood haemoglobin and urine excretion the estimate body fluid shifts, to which individual-specific covariates were added in sequence. RESULTS: The rise in plasma albumin expanded the plasma volume in excess of the infused volume by relocating noncirculating fluid (rate constant k21 ), but it also increased losses of fluid from the kinetic system (kb ). The balance between k21 and kb maintained the rise in plasma albumin and plasma volume at a virtual steady-state for almost 2 hours. The rate constant for urinary excretion (k10 ) was slightly reduced by the preceding surgery, by a marked rise in plasma albumin, and by a high preinfusion urinary concentration of creatinine. The arterial pressure, body weight, and plasma concentrations of C-reactive protein and shedding products of the endothelial glycocalyx layer (syndecan-1, heparan sulfate, and hyaluronic acid) did not serve as statistically significant covariates. CONCLUSIONS: There were no clinically relevant differences in the kinetics of 20% albumin between postoperative patients and volunteers.

Lactate versus acetate buffered crystalloid solutions: Protocol for a scoping review.

BACKGROUND: Intravenous (IV) fluid therapy has become a ubiquitous intervention in everyday clinical practice. Several types of fluid are available including isotonic crystalloid fluids. Among crystalloid fluids, buffered solutions (derivatives of the original Hartmann's and Ringer's solutions) are increasingly recommended as first-line resuscitation fluids. However, the choice between different buffered solutions appears to be difficult with limited data to support the use of lactate vs. acetate buffered solutions. Accordingly, we aim at systematically describing the body of evidence on the use of the different types of buffered crystalloid solutions in hospitalised patients. METHODS: We will conduct a scoping review of all study designs (i.e. no study design will per se be excluded from the proposed review) in accordance with the Preferred Reporting Items for Systematic reviews and Meta Analyses (PRISMA) statement. RESULTS: We will provide descriptive analysis of the included studies/trials, i.e. no meta-analyses will be conducted. We will include studies on adult hospitalised patients receiving IV fluid for any reason. Studies must compare any crystalloid solution primarily buffered with lactate versus any primarily acetate buffered solution. All outcome measures will be reported. The quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. CONCLUSION: This outlined scoping review will provide a summary of the current body of evidence on the use, effects and side-effects of buffered crystalloid solutions. This will provide an important update of the current evidence on the use, of "buffered" crystalloid solutions including evidence of potential benefits and harms.

Effect of restrictive fluid therapy with hydroxyethyl starch during esophagectomy on postoperative outcomes: a retrospective cohort study.

BACKGROUND: To improve prognosis after esophageal surgery, intraoperative fluid optimization is important. Herein, we hypothesized that hydroxyethyl starch administration during esophagectomy reduce the total amount of fluid infused and it could have a positive effect on postoperative complication occurrence and mortality. METHODS: All consecutive adult patients who underwent elective esophageal surgery for cancer were studied. The primary outcome was the development of composite complications including death, cardio-cerebrovascular complications, respiratory complications, renal complications, gastrointestinal complications, sepsis, empyema or abscess, and multi-organ failure. The relationship between perioperative variables and composite complication was evaluated using multivariable logistic regression. RESULTS: Of 892 patients analyzed, composite complications developed in 271 (30.4%). The higher hydroxyethyl starch ratio in total fluid had a negative relationship with the total fluid infusion amount (r = - 0.256, P <  0.001). In multivariable analysis, intraoperatively administered total fluid per weight per hour (odds ratio, 1.248; 95% CI, 1.153-1.351; P <  0.001) and HES-to-crystalloid ratio (odds ratio, 2.125; 95% CI, 1.521-2.969; P <  0.001) were associated with increased risks of postoperative composite outcomes. CONCLUSIONS: Although hydroxyethyl starch administration reduces the total fluid infusion amount during esophageal surgery for cancer, intravenous hydroxyethyl starch infusion is associated with an increasing risk of postoperative composite complications.

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.

The anion study: effect of different crystalloid solutions on acid base balance, physiology, and survival in a rodent model of acute isovolaemic haemodilution.

BACKGROUND: Commercially available crystalloid solutions used for volume replacement do not exactly match the balance of electrolytes found in plasma. Large volume administration may lead to electrolyte imbalance and potential harm. We hypothesised that haemodilution using solutions containing different anions would result in diverse biochemical effects, particularly on acid-base status, and different outcomes. METHODS: Anaesthetised, fluid-resuscitated, male Wistar rats underwent isovolaemic haemodilution by removal of 10% blood volume every 15 min, followed by replacement with one of three crystalloid solutions based on acetate, lactate, or chloride. Fluids were administered in a protocolised manner to achieve euvolaemia based on echocardiography-derived left ventrical volumetric measures. Removed blood was sampled for plasma ions, acid-base status, haemoglobin, and glucose. This cycle was repeated at 15-min intervals until death. The primary endpoint was change in plasma bicarbonate within each fluid group. Secondary endpoints included time to death and cardiac function. RESULTS: During haemodilution, chloride-treated rats showed significantly greater decreases in plasma bicarbonate and strong ion difference levels compared with acetate- and lactate-treated rats. Time to death, total volume of fluid administered: chloride group 56 (3) ml, lactate group 62 (3) ml, and acetate group 65 (3) ml; haemodynamic and tissue oxygenation changes were, however, similar between groups. CONCLUSIONS: With progressive haemodilution, resuscitation with a chloride-based solution induced more acidosis compared with lactate- and acetate-based solutions, but outcomes were similar. No short-term impact was seen from hyperchloraemia in this model.

Safety and efficacy of peri-operative administration of hydroxyethyl starch in children undergoing surgery: A systematic review and meta-analysis.

BACKGROUND: Hydroxyethyl starch (HES) solutions have shown their efficiency for intravascular volume expansion. A safety recommendation limiting their use in adult patients has recently been made. OBJECTIVE: To assess the efficacy and adverse effects of HES when administered intra-operatively to paediatric patients. DESIGN: Systematic review with meta-analyses. Data were analysed using classical mean differences [and their 95% confidence intervals (CIs)] and trial sequential analysis. A Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification was performed for all outcomes. Reviewers extracted valid data, including perioperative total fluid intakes, mortality, renal function, coagulation tests, blood loss and length of hospital and ICU stay. DATA SOURCES: Searches were performed in databases (Pubmed, Embase, Cochrane central register of controlled trials), clinical trials register, and open access journals not indexed in major databases. ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs) published before December 2016 involving paediatric patients who received 6% low molecular weight HES. RESULTS: Nine RCTs involving 530 peri-operative paediatric patients were analysed. Compared with other fluids, HES did not significantly modify the amount of peri-operative fluid administered [mean difference 0.04; 95% CI (-1.76 to 1.84) ml kg], urine output [mean difference -33; 95% CI (-104 to 38) ml kg] or blood loss [mean difference -0.09; (-0.32 to 0.15) ml kg]. Trial sequential analysis determined that the outcomes for peri-operative fluid and urine output were underpowered. All results were graded as very low quality of evidence. CONCLUSION: Intravascular volume expansion with low molecular weight 6% HES did not appear to modify renal function, blood loss or transfusion when administered to children during the peri-operative period. However, given the lack of statistical power and the very low GRADE quality of evidence, more high-quality RCTs are needed to explore these outcomes.

Is the use of hydroxyethyl starch as priming solution during cardiac surgery advisable? A randomized, single-center trial.

INTRODUCTION: The use of cardiopulmonary bypass (CPB) leads to increased fluid filtration and edema. The use of artificial colloids to counteract fluid extravasation during cardiac surgery is controversial. Beneficial effects on global fluid loading, leading to better cardiac performance and hemodynamics, have been claimed. However, renal function and coagulation may be adversely affected, with unfavorable impact on outcome following cardiac surgery. METHODS: Forty patients were randomly allocated to study groups receiving either acetated Ringer's solution (CT group) or hydroxyethyl starch (HES group, Tetraspan®) as CPB priming solution. Fluid balance, bleeding and hemodynamics, including cardiac output, were followed postoperatively. The occurrence of acute kidney injury was closely registered. RESULTS: Two patients were excluded from further analyzes due to surgical complications. Fluid accumulation was attenuated in the HES group (3374 (883) ml) compared with the CT group (4328 (1469) ml) (p=0.024). The reduced perioperative fluid accumulation was accompanied by an increased cardiac index immediately after surgery (2.7 (0.4) L/min/m2 in the HES group and 2.1 (0.3) L/min/m2 in the CT group (p<0.001)). No increase in bleeding could be demonstrated in the HES group. Three patients, all of them in the HES group, experienced acute kidney injury postoperatively. CONCLUSIONS: CPB priming with HES solution lowers fluid loading during bypass and improves cardiac function in the early postoperative period. The manifestation of acute kidney injury exclusively in the HES group of patients raises doubts about the use of HES products in conjunction with cardiac surgery. ( https://clinicaltrials.gov/ct2/show/NCT01511120 ).

Capillary leak syndrome: etiologies, pathophysiology, and management.

In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment.

Use of the Fluid Challenge in Critically Ill Adult Patients: A Systematic Review.

The fluid challenge (FC) aims at identifying patients in whom fluid administration improves hemodynamics. Although the FC has been extensively studied, the implementation and definition of improvement are not standardized. This systematic review of studies published between January 1, 1994 and December 31, 2014 characterizes these key components of the FC for critically ill adult patients, as described in the medical literature in the last 20 years. A literature search was performed using MEDLINE, Embase, and Cochrane. For each study, data were collected on study design, study size, study setting, patient population, and how the FC was administered. Eligibility criteria for FC were (1) the infusion of a definite quantity of fluid, (2) of a specific type, (3) in a fixed time period (expressed as either span or infusion rate), (4) with a defined hemodynamic variable as the target, and (5) for a predetermined threshold. One hundred fifty-seven full-text manuscripts were extracted from 870 potentially relevant studies. The inclusion criteria were met by 71 studies including 3617 patients. Sixty-six studies were from a single center and 45 were prospective observational in format. The most common amount infused was 500 cc, used by 55 (77.5%) studies. The most commonly infused fluids were colloids (62.0%). In 43 (60.5%) studies, the FC was administered between 20 and 30 minutes. A positive response to fluid administration was defined as an increase ≥15% of cardiac index or cardiac output in 44 (62.6%) studies. Static or dynamic physiologic indices were utilized in a minority of studies (16.9%) and safety limits for interrupting the FC are adopted in 4 (5.6%) studies only. This systematic review indicates that the FC most commonly consists in infusing 500 mL of crystalloids or colloids in 20-30 minutes, and considered an increase in cardiac index ≥15% as a positive response. However, definite standards for FC administration and evaluation remain undefined.

Colloids in Cardiac Surgery-Friend or Foe?

OBJECTIVE: The right choice of fluid replacement still is a matter of debate. Recently, two large-scale studies on the use of hydroxyethyl starches (HES) in the intensive care setting have been published, which have caused a huge shift in the daily practice of volume therapy. These results have been applied to patients outside intensive care. The aim of this study was to evaluate the impact this change has had on the outcomes in a large population of cardiac surgery patients, with a focus on the type of colloid infusion. DESIGN: A prospective, registered, observational study, using propensity score matching. SETTING: Cohort study from 3 university hospitals using a common registry. PARTICIPANTS: The study comprised 17,742 patients who were referred for cardiac surgery from 2007 to 2014. INTERVENTIONS: Patients were divided in groups according to perioperative fluid replacement with either crystalloids or colloids. The colloid group was further divided into HES or human albumin (HA). Analyses were based on the following 3 subsections: HES versus crystalloids, HA versus crystalloids, and HES versus HA, with use of propensity score matching or direct matching of cases. Primary outcome parameters were 30-day and 6-month mortality, new postoperative renal replacement therapy, and new cardiac ischemic events. MEASUREMENTS AND MAIN RESULTS: The groups were fully comparable in individual analyses. The use of HES had no impact on new dialysis and 30-day mortality. A Cox proportional regression analysis showed that HES had no impact on 6-month mortality and new postoperative ischemic events. When comparing HA with crystalloid use, a significantly increased risk in crude analysis was demonstrated on all outcome parameters; and when comparing HA with HES, a significantly higher risk was observed in HA patients in mortality parameters and new postoperative, but after adjustment, only the risk of new postoperative dialysis persisted. CONCLUSION: This study underlined the difficulties in establishing hardcore outcome data, even in large cohort studies. The findings seemed to diminish the magnitude of risk when using HES in cardiac surgery patients and seriously questioned the choice of HA when a plasma expander is needed.

Effect of Hydroxyethyl Starch Solution on Incidence of Acute Kidney Injury in Patients Suffering from Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The application of third-generation hydroxyethyl starch (HES) solutions in critically ill patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) was often part of the treatment of delayed cerebral ischemia (DCI). However, there is increasing evidence showing a correlation between the application of HES and the incidence of acute kidney injury (AKI). METHODS: In a single-center retrospective analysis including 81 patients without a preexisting renal disorder suffering from aSAH who had received higher volumes of 6 % HES 130/0.4 due to standard treatment of DCI, the incidence of AKI during intensive care unit (ICU) stay was recorded using AKIN criteria. Furthermore, the course of serum creatinine after discharge from ICU was observed. RESULTS: 6 % HES 130/0.4 was given over a period of 12.9 ± 7.1 days resulting in a cumulative dose of 12543.2 ± 7743.6 mL. Four patients (4.9 %) fulfilled AKIN criteria stage 1 during ICU stay. In two of these patients, serum creatinine was within normal range again on day of discharge. Five patients showed elevated levels of serum creatinine within 1 to 22 months after hospitalization. A correlation between the amount of HES given and the incidence of AKI could not be found. CONCLUSION: The application of 6 % HES 130/0.4 did not lead to an elevated incidence of AKI in patients without an elevated baseline serum creatinine. However, there is still a lack of high-level evidence as prospective randomized trials are missing yet.