BACKGROUND: Granulocyte transfusion is one of the best therapeutic modalities in prolonged neutropenic patients with severe bacterial/fungal infections. Granulocyte harvest using conventional acid citrate dextrose (ACD) anticoagulant (ACD-A) by apheresis is not satisfactory in comparison to the use of hydroxyethyl starch (HES), but the latter is associated with various adverse events, especially with high-molecular-weight HES.
OBJECTIVE: This study aimed to assess the beneficial impact of the use of medium-molecular-weight (MMW)-HES and trisodium citrate combination over ACD-A in granulocyte apheresis when using Spectra Optia.
METHODS: This was a retrospective study comparing granulocyte harvest results with the use of ACD or HES and trisodium citrate combination. All the donors in both the groups received single 600 μg of granulocyte colony-stimulating factor subcutaneous injection followed by 8 mg of dexamethasone tablet 10-12 h and omnacortil 60 mg orally 3 h before harvest. A number of adverse incidents, if any, were observed and noted. Donor/procedure parameters were compared using Mann-Whitney U-test/unpaired t-test.
RESULTS: Granulocyte yield (mean: 3.29 × 1010/unit vs. 4.5 × 1010/unit in the ACD and HES groups, respectively, P ≤ 0.0001) was significantly better in the HES group. The collection efficiency was also better in the HES group (mean: 15.86% vs. 26.70% in the ACD and HES groups, respectively, P ≤ 0.0001) in the ACD and HES groups, respectively. There was no significant adverse event noted in any of these two groups.
CONCLUSIONS: In our study, granulocytes with optimum yield can be easily harvested with Spectra Optia cell separator using 6% HES (MMW) and trisodium citrate combination with standard 12-h interval gap between mobilization and harvest. This strategy can also have no or minimal extra cost burden to patients.

OBJECTIVE: Colloids are added to the priming solution of the cardiopulmonary bypass (CPB) pump to maintain colloid osmotic pressure and prevent fluid overload. This study aimed to compare the effects of 6% hydroxyethyl starch (HES) 130/0.4 and ringer\'s lactate (RL) priming solution on patients\' outcomes undergoing isolated heart valve surgery with CPB.
METHODS: This randomized clinical trial included one hundred and 20 patients undergoing heart valve surgery, and those were allocated into two groups. Patients in the RL group received 1500 mL of RL, and those in the RL + HES group were given 500 mL of HES and 1000 mL of RL.
RESULTS: The patients\' median age was 52 (IQR 42-60) and 50 (IQR 40-61) years in the RL + HES and the RL group, respectively (p = .71). The number of cases that required blood product transfusion in both the operating room and intensive care unit was also significantly higher in the RL + HES group compared to the RL group (RR 2.04, 95% CI 1.50-2.76; p < .01 and RR 1.42, 95% CI 1.01-2.01; p = .05, respectively). Declines in postoperative creatinine levels and platelet counts were higher in the RL + HES compared to the RL group (between-subjects effect p = .007 and p = .038, respectively), while the incidence of acute kidney injury was comparable between groups (RR 0.66, 95% CI 0.13-3.30; p = .55).
CONCLUSIONS: Among patients undergoing heart valve surgery with CPB, 6% HES added to RL for priming compared with only RL increased the risk of the need for blood product transfusion over the hospitalization period.

BACKGROUND: Trauma may be associated with significant to life-threatening blood loss, which in turn may increase the risk of complications and death, particularly in the absence of adequate treatment. Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss to maintain or re-establish hemodynamic stability with the ultimate goal to avoid organ hypoperfusion and cardiovascular collapse. The current study compares a 6% HES 130 solution (Volulyte 6%) versus an electrolyte solution (Ionolyte) for volume replacement therapy in adult patients with traumatic injuries, as requested by the European Medicines Agency to gain more insights into the safety and efficacy of HES in the setting of trauma care.
METHODS: TETHYS is a pragmatic, prospective, randomized, controlled, double-blind, multicenter, multinational trial performed in two parallel groups. Eligible consenting adults ≥ 18 years, with an estimated blood loss of ≥ 500 ml, and in whom initial surgery is deemed necessary within 24 h after blunt or penetrating trauma, will be randomized to receive intravenous treatment at an individualized dose with either a 6% HES 130, or an electrolyte solution, for a maximum of 24 h or until reaching the maximum daily dose of 30 ml/kg body weight, whatever occurs first. Sample size is estimated as 175 patients per group, 350 patients total (α = 0.025 one-tailed, power 1-β = 0.8). Composite primary endpoint evaluated in an exploratory manner will be 90-day mortality and 90-day renal failure, defined as AKIN stage ≥ 2, RIFLE injury/failure stage, or use of renal replacement therapy (RRT) during the first 3 months. Secondary efficacy and safety endpoints are fluid administration and balance, changes in vital signs and hemodynamic status, changes in laboratory parameters including renal function, coagulation, and inflammation biomarkers, incidence of adverse events during treatment period, hospital, and intensive care unit (ICU) length of stay, fitness for ICU or hospital discharge, and duration of mechanical ventilation and/or RRT.
CONCLUSIONS: This pragmatic study will increase the evidence on safety and efficacy of 6% HES 130 for treatment of hypovolemia secondary to acute blood loss in trauma patients.
BACKGROUND: Registered in EudraCT, No.: 2016-002176-27 (21 April 2017) and ClinicalTrials.gov, ID: NCT03338218 (09 November 2017).

BACKGROUND: Hydroxyethyl starch (HES) solutions are used for volume therapy to treat hypovolemia due to acute blood loss and to maintain hemodynamic stability. This study was requested by the European Medicines Agency (EMA) to provide more evidence on the long-term safety and efficacy of HES solutions in the perioperative setting.
METHODS: PHOENICS is a randomized, controlled, double-blind, multi-center, multinational phase IV (IIIb) study with two parallel groups to investigate non-inferiority regarding the safety of a 6% HES 130 solution (Volulyte 6%, Fresenius Kabi, Germany) compared with a crystalloid solution (Ionolyte, Fresenius Kabi, Germany) for infusion in patients with acute blood loss during elective abdominal surgery. A total of 2280 eligible patients (male and female patients willing to participate, with expected blood loss ≥ 500 ml, aged > 40 and ≤ 85 years, and ASA Physical status II-III) are randomly assigned to receive either HES or crystalloid solution for the treatment of hypovolemia due to surgery-induced acute blood loss in hospitals in up to 11 European countries. The dosing of investigational products (IP) is individualized to patients\' volume needs and guided by a volume algorithm. Patients are treated with IP for maximally 24 h or until the maximum daily dose of 30 ml/kg body weight is reached. The primary endpoint is the treatment group mean difference in the change from the pre-operative baseline value in cystatin-C-based estimated glomerular filtration rate (eGFR), to the eGFR value calculated from the highest cystatin-C level measured during post-operative days 1-3. Further safety and efficacy parameters include, e.g., combined mortality/major post-operative complications until day 90, renal function, coagulation, inflammation, hemodynamic variables, hospital length of stay, major post-operative complications, and 28-day, 90-day, and 1-year mortality.
CONCLUSIONS: The study will provide important information on the long-term safety and efficacy of HES 130/0.4 when administered according to the approved European product information. The results will be relevant for volume therapy of surgical patients.
BACKGROUND: EudraCT 2016-002162-30 . ClinicalTrials.gov NCT03278548.

UNASSIGNED: This multicenter retrospective study aimed to compare the effects of HES and gelatin (GEL) on the risk of post-OLT AKI.
UNASSIGNED: A total of 1,672 patients undergoing OLT were enrolled from major transplant centers in China between 2005 and 2013. These patients were divided into three groups: GEL, hydroxyethyl starch (HES), and GEL + HES group.
UNASSIGNED: There was no significant difference in the incidence of post-OLT AKI among the GEL, HES, and GEL + HES groups. The GEL + HES group had a lower incidence of stage II post-OLT AKI than the other two groups. Compared with patients receiving GEL, patients receiving HES did not harbor an increased risk of AKI. Our results showed that MELD score (adjusted odds ratio [OR], 1.579; 95% confidence interval [CI], 1.123-2.219; P = 0.009) and preoperative anemia (adjusted OR, 1.533; 95% CI, 1.212-1.939; P < 0.001) were independent risk factors for post-OLT AKI, and normal preoperative Scr level (vs abnormal; adjusted OR, 0.402; 95% CI, 0.222-0.729; P = 0.003) was independent protective factors for post-OLT AKI.
UNASSIGNED: This large-scale multicenter retrospective study found that the intraoperative use of HES did not increase the overall incidence of post-OLT AKI in patients when compared with GEL, and whether to increase the risk of post-OLT AKI needs to be further explored.

BACKGROUND: Hydroxyethyl starch (HES) solutions increase the risk of acute kidney injury (AKI) in critically ill patients admitted to intensive care unit (ICU) for medical indications. We conducted a cohort study to evaluate the renal safety of modern 6% HES solutions in high-risk patients having cardiac surgery.
METHODS: In this multicentre prospective cohort study, we recruited 261 consecutive patients at high-risk for developing cardiac surgery-associated AKI, based on a Cleveland score ≥ 4 points, from July to December 2017th in 14 hospitals in Spain and the United Kingdom. Multivariable logistic regression modeling and propensity-score matched-pairs analysis were used to determine the adjusted association between administration of HES and AKI.
RESULTS: Of the cohort, 95 patients (36.4%) received 6% HES 130/0.4 either intraoperatively or postoperatively. Postoperative AKI occurred in 145 patients (55.5%). The unadjusted odds of AKI was significantly higher in the HES group, when compared to those not receiving HES (OR 2.22, 95% CI 1.30-3.80, p = 0.003). In multivariable logistic regression models, modern HES was not associated with significantly increased risk of AKI (adjusted OR 0.84, 95% CI 0.41-1.71, p = 0.63). In propensity score match-pairs analysis of 188 patients, the HES group experienced similar adjusted odds of AKI (OR 1.05, CI 95% 0.87-1.27, p = 0.57) and RRT (OR 1.06, CI 95% 0.92-1.22, p = 0.36).
CONCLUSIONS: The use of modern hydroxyethyl starch 6% HES 130/0.4 was not associated with an increased risk of AKI nor dialysis in this cohort of patients at elevated risk for developing AKI after cardiac surgery.

OBJECTIVE: To analyze the efficacy of hydroxyethyl starch (HES) combined with Ulinastatin (Uti) in the treatment of newborns with capillary leak syndrome (CLS).
METHODS: A total of 60 newborns with CLS admitted to four hospitals were selected as the study subjects, and were randomly divided into the control group (n = 30) and the observation group (n = 30) in accordance with the random number table. The control group was treated with HES alone, while the observation group was treated with Uti combined with HES.
RESULTS: At 5 d after treatment, the incidence rates of systemic edema and pulmonary edema, the levels of CRP, NE, and BUN, and the duration for the improvement of systemic edema, pulmonary edema and NICU hospital stay in the control group were superior to those in the observation group, while the 24-h urine output, PaO2 and MAP levels, the levels of A, SCr, ALT, and IL-10 in the observation group were superior to those in the control group (P < 0.05). After 3 months of follow-up after treatment, the mortality rate of newborns in the observation group (13.33%) was lower than that in the control group (36.67%) (P < 0.05).
CONCLUSIONS: HES combined with Uti can effectively alleviate edema, control inflammatory levels, and improve hepatic and renal functions and neonatal survival rate of newborns with CLS.

UNASSIGNED: Fluid therapy in critically ill patients, especially timing and fluid choice, is controversial. Previous randomized trials produced conflicting results. This observational study evaluated the effect of colloid use on 90-day mortality and acute kidney injury (RIFLE F) within the Rational Fluid Therapy in Asia (RaFTA) registry in intensive care units.
UNASSIGNED: RaFTA is a prospective, observational study in Asian intensive care unit (ICU) patients focusing on fluid therapy and related outcomes. Logistic regression was performed to identify risk factors for increased 90-day mortality and acute kidney injury (AKI).
UNASSIGNED: Twenty-four study centers joined the RaFTA registry and collected 3,187 patient data sets from November 2011 to September 2012. A follow-up was done 90 days after ICU admission. For 90-day mortality, significant risk factors in the overall population were sepsis at admission (OR 2.185 [1.799; 2.654], p < 0.001), cumulative fluid balance (OR 1.032 [1.018; 1.047], p < 0.001), and the use of vasopressors (OR 3.409 [2.694; 4.312], p < 0.001). The use of colloids was associated with a reduced risk of 90-day mortality (OR 0.655 [0.478; 0.900], p = 0.009). The initial colloid dose was not associated with an increased risk for AKI (OR 1.094 [0.754; 1.588], p = 0.635).
UNASSIGNED: RaFTA adds the important finding that colloid use was not associated with increased 90-day mortality or AKI after adjustment for baseline patient condition.
UNASSIGNED: Early resuscitation with colloids showed potential mortality benefit in the present analysis. Elucidating these findings may be an approach for future research.
UNASSIGNED: Jacob M, Sahu S, Singh YP, Mehta Y, Yang K-Y, Kuo S-W, et al. A Prospective Observational Study of Rational Fluid Therapy in Asian Intensive Care Units: Another Puzzle Piece in Fluid Therapy. Indian J Crit Care Med 2020;24(11):1028-1036.

BACKGROUND: We aimed to evaluate the effect of limited volume of hydroxyethyl starch (HES) administration on postoperative renal function in patients undergoing cardiac surgery under cardiopulmonary bypass (CPB).
METHODS: One thousand six hundred fifty-seven patients undergoing cardiac surgery under CPB over two years were included. The patients were divided according to the amount of HES administrated during the first 2 days post-surgery; moderate dose HES (≥20 ml/kg) versus low dose HES (< 20 ml/kg). Outcomes were compared by using inverse probability weighting.
RESULTS: Incidence of acute kidney injury (AKI) was higher in the moderate HES group (p = .02). However, new renal replacement therapy (RRT) (P = .30) and early mortality (p = .97) was similar between the groups. When adjusted, the moderate HES use was associated with AKI (OR, 1.66; 95% CI, 1.12-2.44; p = .01), but did not increase the risk of new RRT (OR, 1.27; 95% CI, 0.71-2.18; p = .40) or early mortality (HR, 0.73; 95% CI, 0.29-1.81; p = .50).
CONCLUSIONS: The moderate dose administration of HES (≥20 ml/kg) in the postoperative period following cardiac surgery might be associated with the risk of AKI. However, it was not associated with serious adverse outcomes such as new RRT or mortality. Further randomized controlled studies are needed to validate study results.

OBJECTIVE: To compare the effect of two prophylactic euvolemic fluid strategy regimens on the incidence of cerebral vasospasm and clinical outcomes in patients with aneurysmal subarachnoid hemorrhage (SAH).
METHODS: Ninety-six patients with a basal intravenous intake of 15 mL/kg/day of Ringer\'s lactate solution were included, and an additional 15 to 50 mL/kg/day Ringer\'s lactate (RL-group) or hydroxyethyl starch 130/0.4 solution (HES-group) was administered to maintain the targeted mean arterial pressure. The primary end point was the occurrence of cerebral vasospasm during the first 14 days. The secondary end points were case fatality, Barthel\'s index, and Glasgow Outcome Scores (GOS) at 30 days after SAH.
RESULTS: Cerebral vasospasm developed in 42 patients (43.7%), and nine of these events were severe. The vasospasm rate among the RL- and HES-based groups was 25/48 and 17/48, respectively. For the secondary endpoint, four patients (4%) died by the end of follow-up (two in each group). Unfavorable outcome cases were not different in the RL and HES groups (9 vs. 14, respectively). There was no difference between the Barthel\'s scores at 30 days between the two groups.
CONCLUSIONS: Using starches in a prophylactic treatment strategy in aneurysmal SAH in not supported by the study.The trial was registered at Clinicaltrials.gov under the number NCT02064075.